JJ Notes Physiology - PDFCOFFEE.COM (2024)

Notes ON Second Edition

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CONTENTS 1. GENERAL PHYSIOLOGY............................

2. HEMATOLOGY............................................. 11 3. NERVE-MUSCLE PHYSIOLOGY................. 26 4. CARDIOVASCULAR SYSTEM..................... 36 5. RESPIRATORY SYSTEM............................... 60 6. GASTRO-INTESTINAL PHYSIOLOGY....... 80

Upgraded by . . . . .

Asif Patel

Grant Medical College and Sir JJ group of Hospitals Mumbai '2013

[emailprotected]

Heart-felt thanks to my mother Aasma, & father Nazimuddin Patel for their help and invaluable support.

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7. SPECIAL SENSES...................................... 94

8. RENAL PHYSIOLOGY............................ 107 9. CENTRAL NERVOUS SYSTEM.............. 119 10. ENDOCRINE SYSTEM............................. 153 11. REPRODUCTIVE SYSTEM........................ 172

Previous Years’ papers.......................... 185

I owe gratitude to my friends for their help and passionate involvement !

Abhimanyu Patil, Abhishek Patil, Darshan Kalal, Israr Qadri, Pooja Sawlani, Raosaheb Lokhande, Robin Patil, Shoyeb Admankar, Suman Lamba, Vinay Nanaware, Vishakha Gajre, Yash Mahajan and Others.

Team Anchor 2k15 Ajinkya Agarwal, Anwesha Singh, Aparna Patil, Ayesha Reshamwala, Nikhil Pant, Nikita Borate, Rigved Burungale, Sampada Joshi, Saniya Sahastrabuddhe, Sarvesh Bhala, Siddhesh Sonawane, Urshita Shah, Utkarsh Kumar, Vaibhav Bhandari, Vaidehi Chavan, Vinayak Mishra.

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GENERAL PHYSIOLOGY

Chapter 1

*Q. Define Homeostasis; describe the mechanisms that maintain homeostasis. Homeostasis is defined as maintenance of constancy of internal environment of the body. Internal environment or 'milieu interior' means the environment around the cell i.e. the Extra Cellular Fluid. Various physical and chemical parameters of ECF are pO2, pCO2, pH electrolytes like Na+, K+, Cl+, glucose etc. All the systems of the body participate in homeostasis e.g. Respiratory System maintains pCO2, pO2, etc. C.V.S. : Blood pressure, blood flow Digestive system: Glucose, amino acids etc. Excretory system: Urea, H+ Conc., electrolytes Endocrine system: Glucose Ca+, electrolytes. Nervous system : Temperature, osmolarity, (maintains other systems) HOMEOSTATIC MECHANISMS Negative feedback Mechanisms : Are most important homeostatic mechanism. In these the response is opposite to the initiating stimulus i.e. increase in conc. of a particular substance initiates mechanisms which decrease its conc. back to normal Example: i) pCO2 resp. centre pulmonary ventilation excess washout of CO2 pCO2 (back to normal) ii) BP regulation.

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iii)- Increased Blood Glucose-> glucose falls back to normal.

increased insulin

increased entry of glucose into the cells

blood

CHARACTERSTICS OF NEG. FEEDBACK CONTROL SYSTEM:

CONTROLLED VARIABLE: i.e. the ECF parameter to be regulated e.g. arterial pressure. It has set point or normal value i.e. 100 mm Hg. Any factor that changes the controlled variable from its normal value is called DISTURBANCE. SENSOR OR DETECTOR: - which defects the shift of controlled variable from set point e.g. baroreceptors. INTEGRATOR CENTRE: - which detects the error between actual and decided value and sends signals to effector organ e.g. vasomotor centre. EFFECTOR ORGAN :- which brings about compensatory changes and restores the controlled variable e.g. blood vessels (dilatation) and heart (activity) reduce blood pressure back to normal. GAIN :- is the ratio of compensation to the error (that remains after compensation) It indicates efficiency of control system DAMPING :- Most negative feedback control systems are critically damped and do not show oscillations. Negative feedback mechanisms operate only in a certain range of controlled variable, beyond which they are replaced by positive feedbacks. POSITIVE FEEDBACK MECHANISMS: Response is same as initiating stimulus. Usually lead to worsening of condition (vicious cycle) For example: Blood Loss decreased cardiac output Decreased Coronary blood flow decreased Myocardial Contractility still more decrease in cardiac output. Few positive feedback mechanisms are useful. Suggestions: facebook.com/asifpatel.ggmc

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Ex.1 Oxytocin & uterus contractions. 2. Thrombin splits prothrombin to from more thrombin 3. LH Surge. 4. Opening of Na channels

*Q. Describe the structure and functions of the cell membrane. Structure :Cell membrane is a thin flexible fluid and dynamic membrane that surrounds the cells. Also called plasma membrane. It has a thickness of 7.5 nm to 10 mm It is made up of lipids (4.2%) proteins (55%) and small amount of carbohydrates-(3%) Basically the membrane is a lipid bilayer i.e. :- It is made up of lipids, 2 molecules thick, and the proteins are studded or floating in this lipid bilayer. This concept of cell membrane is called Fluid Mosaic Model. Lipids :Lipids in the membrane are mainly phospholipids like phosphatidylcholine, phosphatidylethanolamine, Sphingomyelin and cholesterol. Each phospholipid molecule has 2 parts: 1) Water soluble polar group containing PO4 2) Fat soluble tail portion made up of two fatty acylchains There phospholipid molecules are arranged in two layers in such a way that their fat soluble hydrophobic ends meet each other in the interior of the membrane and their water soluble polar groups project towards the internal (cytoplasmic) and external surfaces of cell membrane. PROTEINS : Are studded in lipid bilayer and are mostly glycoproteins. There are 2 types of memb. proteins 1) Integral (transmembranous) proteins: which extend through the membrane They act as channels, carriers, receptors, enzymes, cytoskeleton, and cell identity markers. 2) Peripheral proteins: Located on inner or outer surface of membrane and act as receptor proteins or enzymes CARBOHYDRATES :Carbohydrates of cell membrane are in combination with proteins (glycoproteins) or lipid (glycolipids). The carbohydrate portions of these molecules project from outer surface of cell. In some cells these carbohydrate proteins form a loose coat covering the cell called glycocalyx. Carbohydrates in membrane act as receptors, give negative charge to cell surface to cell surface and help in attachment of one cell to another. FUNCTIONS OF CELL MEMBRANE : It acts as lipid barrier and separates ICF from ECF It is selectively permeable and therefore maintains constancy of ICF Its selective permeability also causes development of Resting membrane potential in excitable cells. It is responsible for molecular transport of substances like O2 . CO2, electrolytes like Na+, K+, Cl+, Glucose amino acids etc, by various modes such as diffusion, carrier mediated transport etc. It is also concerned with transport of macromolecules by mechanisms like phagocytosis, pinocytosis etc. Receptors on the cell membrane mediate effects of ext. substance on the cell membrane, drug on the cell through activation formation of second messenger. It contains Major Histocompatibility complex antigens and blood group antigens which differentiate body’s own cells from foreign cells. It helps in attachment of one cell another forming various types of intercellular functions like gap junction tight junction etc. Suggestions: facebook.com/asifpatel.ggmc

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8 In case of muscle fibers it extends deeper into the cells forming t tubules and transmits excitation into the interior. It contains Na+ pump which maintains the volume of the cells. In excitant tissues, it conducts action potentials. It forms the discs in rods and cones containing the photopigment. It helps to maintain shape and size of the cell. Q. Various mechanisms of membrane transport.

1. Diffusion: It is the net movement of molecules of a substance from high conc. to low conc. Because of their kinetic motion. A ) SIMPLE diffusion: is the diffusion of substances by itself (no carrier ) Rate of the diffusion proportional to conc. gradient. a) Diffusion through lipid portion: Occurs in case of lipid soluble substances like O2, CO2 alcohol. Water molecules can also diffuse through lipid portion because of their small size and high kinetic energy (Osmosis). b)Diffusion through membrane channels: -Channels are watery spaces in transmembrane proteins. -Lipid insoluble substances especially electrolytes like Na+,K+ pass through these channels.

-Channels are specific for ions e.g. Na+_ channels for Na+ ions etc -Some channels have gates which are flap like extensions of protein molecules. -these gates open in response to1- Change in voltage- Voltage gated channels eg. Na+, Ca+ channels 2- chemical subst. –Ligand gated channels eg. Ach gated channels 3- Stretch-Stretch activated channels eg. Some Na+ channels B) Facilitated Diffusion: Is the diffusion of a substance from high conc. to low conc. with the help of carrier protein. Substances like glucose and amino acids are transported by this mechanisms Mechanism: Here the substance combines with carrier protein on one side of the membrane and the combination causes conformational change in carrier and the substance is released on other side of membrane Characteristics: a) carrier protein is specific for a particular substance (stereospecificity) b) rate of transport has a maximum limit called V max (saturation) e.g. TmG. c) subject to competitive and non competitive inhibition d) no energy required. 2) Active Transport: Is a carrier mediated transport in which a substance is transported against conc. or electrical gradient (uphill). The process requires energy (ATP) A) Primary Active Transport Here energy is derived directly from breakdown of ATP by the carrier protein which has ATPase activity. -Examples: Na+ K+ pump Ca+ pump, Iodide pump etc. -Mechanism of action of Na+ K+ pump. Is a protein that transports 3 NA + ions out of and 2 K+ions into the cell. Suggestions: facebook.com/asifpatel.ggmc

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When Na + ions bind on its inner surface and 2 K+ ions on its outer surface, ATPase function is activated, ATP is split and released energy causes conformational change in protein molecule so that Na+ ions are extruded and K+ ions taken into the cell. Characteristics : 1 Specificity 2 V max 3 Competitive inhibition B) Secondary Active Transport Here energy is derived secondary from ionic conc. Gradient created by primary active transport Carrier protein doesn’t have ATPase activity It has Two types: 1 –Co transport 2 –Counter transport Co transport(symport) Example – Na+ Glucose co-transport in renal tubular cells. Here glucose is transported by secondary active transport along with Na + ions into the cell by the same carrier protein. -Na + ions enter the cell due to electrochemical gradient created by active transport of Na+ ions. Counter transport (Antiport) Example - Na+ H+ counter transport -Here H+ ions are transported out of the cells in exchange for Na+ ions that enter the cells by the same carrier protein TRANSPORT OF MACROMOLECULES: A) Endocytosis a) phagocytosis- Is the mechanism by which cell engulfs solid particulate matter. The process starts with contact of substance with receptors on cells(receptor mediated phagocytosis) leading to formation of phagocytic vacuole. b) Pinocytosis– Here the cell engulfs liquid material (specially proteins) to form pinocytic vesicle B) Exocytosis a) Reverse Phagocytosis: Phagocytosis in opp. direction b) Emiocytosis: Pinocytosis in opp. direction *Q. FACILITATED DIFFUSION Definition: It is a type of membrane transport in which a substance diffuses through the cell membrane with the help of a carrier protein also called carrier mediated transport. Mechanism- The substance to be transported combines with the receptor site present on the carrier protein on one side of membrane. The combination causes rapid conformational change in carrier protein, so that the substance is released on the other side of the membrane. E.g. Transport of Glucose, amino acids etc. into the cell. Characteristic features: 1. Here the substance is always transported along the conc., electrical or pressure gradient i.e. from high conc. to low conc. 2. The process doesn’t require energy. 3. This mode of transport is used for those substance which cant diffuse through lipid bilayer or through channels. 4. Specificity: Carrier protein is specific for the substances to be transported 5. The rate of transport reaches a maximum limit called Vmax which is due to saturation of carrier protein and time required for Suggestions: facebook.com/asifpatel.ggmc

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10 conformational change. For Example-transport maximum for glucose = 375mg/min 6. Subject to competitive inhibition eg. Sugars like mannose galactose can compete with glucose for the same carrier protein and decrease rate of glucose transport. 7. Subject to Non-competitive inhibition in which a second substance competes for receptor site and blocks it. 8. Certain substances can accelerate the process. Eg. Insulin increases activity of glucose transporter proteins like GLUT1 and GLUT5 *Q. SODIUM-POTASSIUM PUMP:

Sodium pump is a carrier protein in the cell membrane of almost all cells in the body. It actively transports 3 Na+ ions out of cell and 2 K+ ions inside the cell. It also has ATPase activity, hence called Na+ K+ ATPase Structure : Sodium pump is a complex protein made up of 2 subunits: 1. A large catalytic Subunit with a mol. wt. Of 100000. It has 3 Na+ binding sites on its cytoplasmic surfaces and 2 k+ binding sites on its outer surfaces. It also has ATPase activity 2. A β subunit with mol.wt. of 50000. It is glycoprotein in nature and its exact function is not known. ACTION: Combination of 3 Na+ ions with receptors on inner surface and two K+ ions on outer surface stimulates ATPase activity. ATP is broken down to ADP in presence of Mg++ ions and the released energy causes conformational change in carrier protein molecule. So that Na+ ions are brought to exterior and K+ ions pass into the cell against their conc. gradient. Since the carrier protein itself has ATPase activity, this is an example of primary active transport. It is also an example of antiport mechanism because Na+ and K+ ions move in opp. direction FUNCTIONS: 1)By causing active transport of Na+ ions out of cell and K+ ions into the cell, it maintains the conc. Difference of these ions across the cell membrane which forms the basis of resting membrane potential and excitability. 2)Electrogenic Pump-It causes net loss of one positive ion from the cell in one cyclical activity and thus contributes to the negativity inside the membrane (coupling ratio 3:2). 3) Maintains cell volume- It keeps osmotically active Na+ ions out of the cell and prevents accumulation of water and swelling of cells. 4) Primary active transport of Na+ ions provides energy for secondary transport of substances like glucose, amino acids etc. 5) It is also the Mechanism for absorption of Na+ ions in intestinal and renal epithelial cells.

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HAEMATOLOGY

Chapter 2

*Q. Describe various functions of blood. Blood is the circulating extra cellular fluid composed of plasma and suspended cells i.e. RBCs, WBCs, and platelets. Functions : A)Transport functions 1. Oxygen transport- Oxygen is transported from lungs to tissues by the hemoglobin in the RBCs forming a loose reversible combination (oxyhemoglobin) 2. Carbon dioxide transport- CO2 is transported from tissues to the lungs for elimination of bicarbonates and as carbaminohemoglobin 3. Transport of nutrients-Nutrients like glucose, amino acids etc are transported from the intestines where they are absorbed to the cells for utilization and storage. 4. Transport of metabolic end products like urea, uric acid etc. from the cells to the kidneys for elimination. 5. Transport of hormones and ions: By transporting, hormones & ions, blood acts as chemical communication system and provides the necessary feedback pathway for controlling the secretion of these hormones. 6. Transport of metals : like Iron(transferrin); Copper (ceruloplasmin) etc. Other functions : B. Helps in maintaining body temperature : This function is facilitated by various properties of blood like high specific heat, high conductivity and high latent heat of evaporation.. C. Maintenance of acid-base balance: Blood contains various buffers such as hemoglobin in the RBCs and the phosphate, bicarbonate and proteins in the plasma which prevent change in hydrogen ion concentration. D. Defensive function a) Phagocytes in blood, monocytes remove bacteria and foreign agents. b) B lymphocytes produce immunoglobulins (antibodies) which attack specific bacteria. c) T lymphocytes can directly or indirectly destroy foreign cells in the body including tumor cells. d) Complement system of enzymes present in plasma attack bacteria, when activated. E. Hemastatic function : Various components of blood help in preventing blood loss. For example, platelets from platelet plug which seals small openings in blood vessels, plasma proteins like fibrinogen, prothrombin etc. help in formation of clot. F. Tissue fluid formation : Proteins(especially albumin) exert colloid osmotic pressure and regulate the process of tissue fluid formation G. Storage function : Glucose, amino acids and electrolytes like Na, Ca, Cl etc. are present in blood in large quantities and act as ready source when tissues require them. H. Water present in blood is in exchangeable with tissue fluid and helps in replenishment of tissue fluid. The volume of blood in blood vessels and its viscosity contribute to blood pressure. *Q. Describe the stages of Erythropoiesis? How is it regulated? Erythropoiesis is the process of formation of Red Blood Cells from primitive stem cells. Sites In Fetus: Yolk sac (up to 3months), liver and spleen(3-6 months)and bone marrow (after 6 months) Adults: Flat bones like sternum, ribs, vertebrae, pelvic bones etc,

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12 Stages: 1.Pleuripotent hemopoietic stem cell is most primitive cell in the bone marrow and is capable of forming all types of blood cells. It is large(18-30 microns)cell with large nucleus and thin rim of deep blue cytoplasm. 2.Committed Stem Cell of myeloid series: is formed by differentiation of pleuripotent cell and is capable, of forming RBC s, granulocytes, monocytes and megakaryocyte. Has same appearance as pleuripotent cell. 3. Progenitor cells: Can form only RBCs a) burst forming unit Erythrocyte (BFU-E) cell: So called because it forms bursts of RBCs in tissue culture. It gives rise to CFU-E cell. b)Colony forming Unit Erythrocyte (CFU-E) cell: Forms colonies of RBCs in tissue culture. These progenitor cells differentiate to form Pronormoblasts. 4. Pronormoblast (Proerythroblast): First morphologically recognizable cell belonging to RBC series. It is a large (15-20 microns)cell with scanty deep blue cytoplasm. Nucleus shows prominent nucleoli and chromatin reticulum. 5.Early normoblast (Basophil erythroblast) : Formed by multiplication of pronormoblast. It is a similiar cell with large nucleus nucleoli disappear, cytoplasm becomes lighter. 6.Intermediate normoblast (Polychromatic erythroblast (Polychromatophil erythroblast) :10-14 microns in diameter. There is condensation of nuclear chromatin. Hemoglobin appears in cytoplasm which becomes polychromatophilic. 7.Late normoblast(Orthochromatic erythroblast): Smaller (9-10 microns)in size. Nucleus becomes smaller and deeply stained i.e. pyknotic nucleus. Later the nucleus disappear(Karyorrhexis). Hemoglobin content increases and cytoplasm becomes eosinophilic. The cell looses capacity to divide. 8. Reticulocyte :8-9 microns, no nucleus. Supravital staining shown network like appearance due to remains of basophilic cytoplasm and organelles, some reticulocytes escape into circulation(1% RBCs) 9. Mature RBC:7.5 microns in diameter, fully hemoglobinised reticulum disappears. Enters circulation. The entire process of erythropoiesis takes about 8 to 10 days. REGULATION: Erythropoiesis is precisely regulated in accordance with the oxygen needs of the tissue. Various condition like blood loss, cardiac failure, pulmonary diseases, high altitude and anemia reduce oxygen delivery to tissues and thus produce hypoxia. In such conditions, kidney and liver cells secrete a substance called Renal erythropoeitic Factor which acts on a plasma protein called Erythropoietinogen to form a glycoprotein hormone called Erythropoietin. Erythropoietin then stimulates erythropoiesis by1. Promotes conversion of pleuripotent cells into committed stem cells of myeloid series. 2. Conversion of CFU-E cells into pronormoblasts. 3. Accelerates maturation process. 4. Stimulates haemoglobin synthesis. In addition, burst promoting activity (BPA) produced by monocytes and lymphocytes also stimulates Erythropoiesis. *Q. Describe the factors essential for Erythropoiesis. Erythropoiesis is the process of formation of RBCs from primitive stem cells. Various factors essential for erythropoiesis are: Suggestions: facebook.com/asifpatel.ggmc

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1. Erythropoietin : Erythropoietin not only stimulates erythropoiesis in hypoxia but its normal circulating levels are essential for normal erythropoiesis. Chronic renal diseases are associated with anemia due to failure of production of normal amount of erythropoietin. Formation: In conditions of hypoxia cells of kidneys and liver produce renal erythropoietic factor which acts on plasma Erythropoietinogen to form erythropoietin. Actions: Stimulates maturation of CFU-E cells into pronormoblasts and hastens synthesis of hemoglobin 2. Vitamin B12 (Cynocobalamin): It is essential for synthesis of DNA in erythropoiesis. It helps in conversion of deoxyuridilate to deoxythymidilate and also acts as donor of methyl group in cellular

reactions. Source: Meat, milk, liver. Daily requirements: 1-3 micrograms. For the absorption of B12 (extrinsic factor), an intrinsic factor is produced by parietal cells in gastric mucosa is essential. In B12 deficiency due to defective DNA synthesis, there is failure of multiplication as well as maturation of cells leading to formation of large abnormal cells called megaloblasts. 3. Folic acid: Along with Vit B12 (folic acid) is essential for synthesis of DNA. Therefore deficiencies of folic acid also causes maturation failure anemia. Source- Vegetables, fruits, meat. Daily requirement-50 micrograms. 4. Iron :It is essential for synthesis of haem part of hemoglobin. Iron in ferrous state combines with protoporphyrin IX to form haem. Oxygen is transported, attached to one of the covalent bonds of ferrous atom in the hemoglobin molecule. Source: meat, peas, leafy vegetables, jaggery. Daily requirement:Males-1mg; Females-2mg Absorption of iron is facilitated by a protein called Apotransferrin present in the bile. Deficiency of iron (absolute or relative)causes defective hemoglobin synthesis and leads to microcytic hypochromic anemia. 5. Vit B6 and Vit C: These are essential for erythropoiesis because of their role in cellular enzymatic reactions and Vit C keeps the iron in ferrous form. 6. Copper, Cobalt and manganese : these are essential because they act as components of various coenzymes in cellular reactions(catalysts). 7. Hormones like thyroxine and cortisol have stimulating effect on erythropoiesis either because of their protein anabolic effect or by stimulating production of erythropoietin. Myxoedema is associated with anaemia. 9. Bile Salts: Essential for absorption of metals. Q. Describe the Functions of Neutrophils. Neutrophils attack and destroy invading bacteria. Various stages involved are: 1. Margination: Neutrophils stick to endothelial cells of blood vessels. 2. Diapedesis : They squeeze through gaps between endothelial cells and enter tissue spaces. 3. Chemotaxis: They are chemically attracted towards bacterial toxins, complement C5,etc. Suggestions: facebook.com/asifpatel.ggmc

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14 4. Phagocytosis : On reaching the bacteria neutrophils engulf them. Phagocytosis is facilitated by rough surface of particle, loss of protein coat and by opsonins like IgG, complement C3,etc. 5. After phagocytosis, Bacteria are killed and digested by the enzymes like myeloperoxidase with formation of lethal ions like superoxide, hypochlorite ions, etc. 6. Lactoferrin secreted by neutrophils inhibits bacterial growth and also multiplication of CFU-GM cells thus controlling neutropoiesis.

*Q. Describe the classical ABO blood groups & their importance: ABO blood group system is a classification of blood depending upon presence of certain antigens called agglutinogens on the surface of red blood cells. It was discovered by Karl Landsteiner in 1901. Agglutinogens: There are 2 agglutinogens of ABO system, A and B. If A agglutinogen is present on the RBC of an individual, he belongs to the blood group A; if B his blood group is B; if both are present blood group is AB and if none is present, it is O blood group. Blood group A is further divided into A1(has antigen A and A1) and A2(has only A antigen) Chemistry: Agglutinogens A& B are mucopolysacharides and their specificity lies in the carbohydrate moiety). Inheritance: Presence of these genes is decided by heredity. These are 3 corresponding genes A (which causes formation of A antigen on RBCs) gene B (B antigen) and gene O (no antigens on RBCs) Possible Genotypes and their phenotypes AA A AO A BB B B0 B AB AB OO O Agglutinins of the AB0 system :Are the antibodies present in plasma which are capable of agglutinating (clumping) the RBCs containing corresponding agglutinogen. They are of 2 type: Anti A and Anti B. According to Landsteiner's law "If a particular agglutinogen is present on RBCs of an individual (eg. A), the corresponding agglutinin (i.e.Anti A) is always absent in plasma. If an agglutinogen is absent, corresponding agglutinins are always present. Suggestions: facebook.com/asifpatel.ggmc

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15 Composition of Blood groups Blood Group agglutinogen Aggulutinin A A Anti B B B Anti 'A AB A and B Nil O Nil Anti A & Anti B Anti A and Anti B agglutinins are gamma globulins. They occur naturally and are formed due to exposure to A and B antigens which are widely present in nature food, water, air etc. Their titre is low at birth, starts rising from 2nd to 8th month and reaches peak between 8 to10 years. Significance of Blood Groups :1. Blood transfusion: Knowledge of blood groups is essential to avoid mismatched blood transfusion. Before transfusion donor's cells are mixed with recipient's serum (Major Cross Matching) and donor's plasma with recipient's cells (minor cross matching) and examined for agglutination. Reaction between donor's cells and recipients plasma is more important. Hence, if donor's cells do not contain any antigen( 0 group ), such a blood can be given to any recipient (formerly called Universal donor). Similarly if there are no agglutinins in recipients' plasma (AB group), he can receive blood from any group (Universal recipient). Mismatched blood transfusion causes agglutination of donor's cells by haemolysis leading to jaundice, haemoglobinuria, acute renal shutdown, uremia and may cause death. 2. Medicolegal importance: Blood stains can be typed and matched with that of victim or assailant. 3. Paternity Test: To rule out paternity in cases of disputed parentage. For example if child's blood group is 'O', whatever may be mother's group, father's group can never be 'AB'. 4. Identification of individuals and missing babies in maternity ward. 5. Racial studies: To trace common ancestry. 6. Anthropological studies. 7. Disease prevalence: Some blood groups have higher incidence of some diseases eg. Peptic ulcer in 'O', Gastric cancer in 'A' group etc. Similarly Duffy negative persons are resistant to malaria. 8. Infertility Studies. *Q. Describe Rh Blood group and its clinical significance: Rh group is a blood group system depending upon presence or absence of Rh antigen on red blood cells. It was discovered by Landsteiner and Weiner in 1940 . The name Rh is derived from its presence in the RBCs of Rhesus monkey . Rh antigen (Rh factor) :- There are six types of Rh antigens C, c, D, d, E, e of these D (and C E) is strongly antigenic, others have mild antigenicity . A person contains 3 of these antigens on his RBCs, one from each pair, that is C or c, D or d, E or e. For Example, cDe or Cde or cdE etc. Inheritance : Synthesis of these antigens on the RBCs is inherited from parents . There are 3 pairs of genes; Cc, Dd, Ee. C,D,E are dominant and c,d,e are recessive genes. Each chromosome contains one gene from each pair. Therefore Rh genotypes will be Cde/CDe etc. Incidence: Rh positive- 95%, Rh negative- 5% Rh antibodies :- are the antibodies capable of agglunating the cells containing Rh antigen . They belong to IgG type of immunoglobulin and can cross the placenta . They are not present in plasma naturally like Anti A or Anti B antibodies, but are formed in Rh negative persons only after exposure to Rh antigen in conditions like. 1.Transfusion of Rh positive blood into Rh negative person .2. In Rh negative mother having Rh positive fetus . Clinical significance : Rh incompatibility can lead to 1.Erythroblastosis Fetalis or Hemolytic disease of Newborn : Results from Rh incompatibility between mother and fetus where mother is Rh negative and fetus as Rh positive . During first pregnancy, Rh antibodies are not formed, but at the time of parturition, there is some Suggestions: facebook.com/asifpatel.ggmc

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16 mixing of fetal blood with maternal blood and mother is exposed to Rh antigen (Sensitization). She, therefore, starts forming Rh antibodies. In subsequent pregnancies with Rh positive fetus, the titre of antibodies increases and they cross the placenta, enter the fetal circulation and agglutinate fetal red cells . Agglutination is followed by hemoglobin which is converted into bilirubin by macrophages. Clinical features :- 1. New born baby is severely jaundiced due to rise of bilirubin . 2. Bilirubin may be deposited in the neurons of motor areas of brain causing mental impairment or motor dysfunction later in life (Kernicterus) . 3. There is severe anemia and oxygen delivery to the cells is reduced . 4. There is strong stimulation of erythropoiesis producing enlargement of liver and spleen. 5. Some of the immature forms of RBCs i.e. erythroblasts appear in circulation . 6. Sometimes there is severe oedema (hydrops). 7. Death may occur due to severe anemia. Treatment :- Exchange transfusion in which about 400 ml of Rh negative ABO compatible blood is infused into one arm slowly and Rh positive fetal blood removed from other arm . Prevention :-1. Administration of Anti Rh antibodies to mother immediately after delivery to prevent exposure to Rh antigen (Desensitization) . 2. Proper marriage counseling . 2. Transfusion reaction due to Rh incompatibility :- Is characterized by agglutination of donor's Rh positive cells followed by hemo4lysis and jaundice .There may be acute renal shut down .

Q. Describe the morphology, functions and fate of Red blood cells. Morphology: Red blood cells are non-nucleated, circular, biconcave disc shaped cells present in blood . they are thinner at the centre and thicker along periphery .The average diameter of RBC is 7.5 microns, its thickness is 1 micron in the centre and 2.2 microns along periphery . The surface area of a single cell is 125 square microns and average volume is 85-90 cubic microns (MCV) The biconcave shape of cell is due to absence of nucleus and also due to presence of a protein called spactrin attached on the inner aspect of cell membrane . this biconcave shape has many advantages like: 1. It provides large surface area .2. Haemoglobin forms a thin layer and is closer to the surface. 3. It enables the cell to fold upon itself while passing through to narrow capillaries. 4.Permits larger osmotic volume changes cell organelles like endoplasmic reticulum, mitochondria, lysosomes and Golgi complex are absent in adult RBCs . Composition:- It is made up of water (65%) and solids (35%)of the solids, haemoglobin forms 33% to34% of cell weight and is attached to the stromal network other solids include structural proteins, phospholipids 2-3 DPG and cholesterol . Functions:1. Transport of oxygen : oxygen is transported by hemoglobin forming loose reversible compound oxyhemoglobin which is formed in the lungs and dissociates in the tissues releasing oxygen to the cells. Here the oxygen is carried in molecular form attached to covalent bond of ferrous atom in hemoglobin normally 100ml arterial blood carries 21 ml of oxygen. 2. Transport of carbon dioxide: CO2 is transported as carbamino haemoglobin and also as bicarbonates in RBCs and plasma .The enzyme carbonic anhydrase catalyzes the formation of bicarbonates in the RBCs. 3.Buffer:- Hemoglobin in RBCs acts as buffer and prevents changes in H+ ions concentration. 4.Viscosity :-RBCs contribute to this viscosity of blood which is an essential component of peripheral resistance and haemodynamics 5. Source of bile pigment :- Haemoglobin in RBCs form bile pigments like bilirubin and biliverdin Fate of RBCs :Average life span of RBCs is 120 days. As the cell becomes senile its ATP production suffers and due to lack of energy, sodium pump in the cell membrane fails causing accumulation of Na+ ions. Therefore cell becomes abnormal in shape (poikilocyte). Such senile cells with fragile membranes rupture easily while passing through spleen and their fragments are phagocytized by R. E. cells . In these cells, the released hemoglobin is converted into straight chain compound called choleglobin which then splits into haem and globin . Suggestions: facebook.com/asifpatel.ggmc

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The globin chains are broken down into amino acids by the proteases in R. E. cells The iron present in haem is released into plasma where it is transported as transferrin either to bone marrow for resynthesis of hemoglobin or to liver for storage as ferritin or hemosiderin The remaining part of haem forms biliverdin which is then reduced to bilirubin and released from R. E. cells. Bilirubin is transported with albumin in plasma and carried to hepatic cells where it is conjugated with glucuronic acid and sulphate to form bilirubin glucuronide and bilirubin sulphate. This conjugated bilirubin is then excreted through the bile into intestine where it is converted into Stercobilinogen by bacterial action. Some of conjugated bilirubin is reabsorbed into the blood and excreted into the urine in the form of Urobilinogen. *Q. Define Immunity. Discuss the role of lymphocytes in immunity. Definition: Immunity is the ability of the body to resist infection (invasion) caused by foreign agents and to neutralize their harmful effects on the body. It is a function of lymphocytes. There are two types of Immunity:

A) Humoral Immunity: It is due to B lymphocytes. In late fetal life and in the newborn, these cells are processed in the liver and bone marrow (Bursa of Fabricatus in birds) to produce antibodies. Each B lymphocyte is specific for a particular antigen. Response of B lymphocytes: Foreign antigen is first ingested and processed by the tissue macrophage and presented to specific B lymphocyte which then proliferates to form (1) Memory B cells of that clone and (2) Lymphoblasts which differentiate into plasmablasts which then multiply to form plasma cells. The plasma cells then produce immunoglobulins (antibodies) which attack foreign agent. Interleukin 1 produced by macrophages and interleukin 4,5 and 6 produced by helper T cells facilitate the growth of B lymphocytes and production of anti bodies. Immunoglobulins are of 5 types: IgG, IgA, IgM,IgE and IgD (GAME'D). Each immunoglobulin molecule is Y shaped and made up of 2 heavy and 2 light chain. Each chain has a variable and a constant fraction and he specificity lies in the variable fraction. Various ways in which antibodies react with antigen and destroy them are: a) Direct Antigen – Antibody reactions producing: (1) Agglutination of bacteria. (2)Precipitation of bacterial toxins(3)neutralization of toxic sites of organism. (4) lysis, that is disintegration of organism. b) By activation of complement system: It is a system of 11 enzymes present in plasma in inactive state(C1 to C9, B and D). Antigen-antibody reaction reaction activates complement C1 which then brings about sequential activation of other complements. The activated complements then attack and destroy antigenic agents by mechanisms like 1. Opsonisation (C3b) 2. Lysis. 3. Agglutination. 4. Neutralization of viruses 5. Chemotaxis (C5). 6. Activation of mast cells. CELLULAR IMMUNITY : Is due to T lymphocytes and is affective against -chronic infections and foreign cells like tumors, grafts and virus infested cells . These T lymphocytes are processed in thymus in late fetal life and in new born. Each T lymphocyte is specific for particular antigen and contains. Surface receptor proteins (T cell markers). Suggestions: facebook.com/asifpatel.ggmc

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18 Activation of T cell: When a foreign antigen is presented by a macrophage to its specific T cell, binding of antigen to the T cell causes its activation. It then proliferates and forms large number of T lymphocytes of that clone. There are 4 types of such activated T cells. 1. Helper T cells (T4 cells): these cells secrete various chemicals called Lymphokines like (a) Interleukin 2 which causes growth and proliferation of cytotoxic and suppressor T cells. (b) Interleukins 4,5 and 6 : Stimulate antibody production by B lymphocytes. (c) Interferon: destroys viruses. (d) CSF -GM: stimulates leucopoiesis (e) Migration Inhibition Factor: inhibits migration of macrophages. 2. Suppressor T cells (T8 cells) : These cells suppress the function of helper and cytotoxic cells and therefore limit the immune response. They are also responsible for immune (self) tolerance. Helper T cells and suppressor T cells are called Regulatory T cells 3. Cytotoxic (Killer) T cells: Can directly attack and destroy foreign cells. They attach to foreign cell, release a protein called Perforin which makes a hole in foreign cell through which cytotoxic enzymes are released into the foreign cell causing its destruction. 4. Delayed type of Hypersensitivity T cell: are activated after few days or weeks and are responsible for delayed reactions like graft rejection. Cytotoxic and DTH T cells are called as Effector T cells. Applied Physiology: In Acquired Immuno Deficiency Syndrome (AIDS), HIV attacks Helper T cells and suppresses humoral as well as cellular immunity.

*Q. Define Hemostasis. Describe the process of blood loss from the body. Mechanics leading to hemostasis are: 1. Spasm of injured blood vessel due release of vaso constrictor substances and local myogenics spasm. 2. Platelet plug formation: in which platelets adhere to each other forming a plug which seals the opening in blood vessel. 3. Coagulation. 4. Growth of fibrous tissue into clot. COAGULATION: Definition : It is the process in which fluid blood is converted into a semisolid jelly like mass called clot. It is the property of plasma.

Coagulation occurs in 3 stages: I) Formation of Prothrombin activator:

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Can occur via 2 pathways : a) Extrinsic pathway :

It is initiated by tissue damage which results in release of complex substances called tissue thromboplastin. They include lipoproteins and membrane phospholipids. The lipoprotein part combines with Factor VII and this along with tissue phospholipids acts on factor X in presence of Calcium ions to form activated factor X. Activated factor X then combines with tissue phospholipids and with factor V in presence of Ca ions and forms a complex substance called Prothrombin activator. Here factor V is activated by thrombin. b) Intrinsic Pathway: Initiated when there is damage to blood itself. Contact of blood with exposed collagen fibers brings about activation of factor XII and also of platelets which release lipoprotein (Platelet factor III) and phospholipids. Activated factor XII acts as proteolytic enzyme and converts factors IX into activated factor IXa. Activated factor IX then forms a complex with factor VIII, phospholipids and platelet factor III and in presence of calcium ions converts factor X to activated factor Xa, which then combines with factor V and phospholipids in presence of calcium ions and forms prothrombin activator. II) Conversion of prothrombin to thrombin: Prothrombin is an alpha 2 globulin present in plasma (15 mg per 100ml). It is synthesized in the liver and Vit. K is essential for its synthesis. Prothrombin activator acts as proteolytic enzyme and in the presence of Ca ions, splits

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20 prothrombin into smaller unit called thrombin. III) Conversion of fibrinogen into fibrin: Thrombin is also proteolytic enzyme. It acts on soluble plasma protein fibrinogen and splits 4 small peptides from each fibrinogen molecule to form insoluble fibrin monomers, which then polymerize spontaneously forming long fibrin threads . The network of fibrin threads along with trapped plasma, RBCs, WBCs and platelets forms the clot that effectively seals the opening in the vessel wall and stops bleeding. Stabilization of clot: Is brought about by factor XIII (fibrin stabilizing factor) present in the plasma which forms cross linkages between adjacent Fibrin threads. Thus whole process of coagulation involves sequential activation of (cascade) coagulation factors in plasma ultimately forming fibrin threads and is complete in 3 to 6 minutes. Clot retraction is a process in which the clot becomes smaller and more firm and exudes serum. It occurs in 30 to 60 minutes and is due to platelets. Applied Physiology: Hemophilia a clinical condition that results from deficiency of factors VIII,IX and XI of genetic origin and is characterized by bleeding in joints and prolonged coagulation time.

Q. Iron Deficiency Anemia Anemia is a condition characterized by reduced Oxygen carrying capacity of blood either due to decrease in hemoglobin content of cells or decrease in the number of RBCs. Iron deficiency anaemia results from deficiency of iron which may be absolute (no iron in the diet) or relative (where iron requirement is greater e.g pregnancy, bleeding disorders etc.) Daily requirement: 1 mg per day. Dietary Sources: Green leafy vegetables, peas, meat, jaggery etc. Absorption of iron in small intestine is facilitated by a protein called apotransferrin present in the bile. Role of iron :Iron is essential for synthesis of haem part of hemoglobin. Ferrous atom in hemoglobin carries oxygen and carbon dioxide. 1 gm of hemoglobin contains 3.34 mg of iron. Deficiency of iron therefore depresses hemoglobin synthesis and erythropoiesis. Clinical features: There is extreme pallor of skin and conjunctiva. Nails are spoon shaped (koilonychia). There may be atrophic glossitis (Plummer Vinson Syndrome). There are other manifestations like breathlessness, on exertion, palpitation, giddiness, hypotension, tachycardia, increased E.S.R. etc Treatment: Administration of oral iron in the form of ferrous sulphate. b) intramuscular iron. c)Blood transfusion if anemia is severe. Q. FUNCTIONS of Eosinophils

A)Antiparasitic function:-Eosinophils migrates to the parasites in the tissues, attaches to them and kills them by releasing hydrolytic enzymes and peroxidases with formation of lethal superoxide ions. In addition, major basic protein has larvicidal action. B)Antiallergic function:-Eosinophils are attracted towards allergic inflammation sites by eosinophilic chemotactic factor which is probably histamine especially, the histamine produced by mast cells and basophils. They also phagocytize antigen antibody complexes of allergic reaction. Thus eosinophils control allergic inflammation. Applied Physiology:-Eosinophilia is seen in allergic conditions like bronchial asthma, hay fever, exema, tropical eosinophilia and in parasitic infestations like hookworms, round worms, tapeworms and filariasis. Eosinopenia is seen in Cushing's syndrome excess clinical dose of cortisol and aplastic anemia. *Q. HAZARDS OF MISMATCHED BLOOD TRANSFUSION: Suggestions: facebook.com/asifpatel.ggmc

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Prior to transfusion it is absolutely essential to study the compatibility between donor's blood and recipients blood by a procedure called 'Cross matching' in which donor's RBCs are mixed with recipients plasma(major plasma matching)and recipients RBCs with donor's plasma(minor). Absence of agglutination indicates compatibility. Transfusion of incompatible blood produces following complications : 1. There is Agglutination of donor's RBC's by the agglutinins is recipients plasma. The clumps of RBC's block peripheral capillaries. 2. The agglutinated RBC's are hemolysed by the R.E. cells with release of large quantities of haemoglobin in circulation some of which binds with haptoglobin and some remains free. 3. There is increased destruction of hemoglobin causing rise in bilirubin content of blood and jaundice. 4. Agglutination reaction causes release of certain toxic substance which cause 1.renal vasoconstriction and 2.circulatory shock. Both these factors decrease blood flow to kidney. 5.Acute renal shutdown can occur due to precipitation of filtered hemoglobin in the renal tubules in addition to the above factors producing anuria, uremia, coma and even death. Other hazards(not due mismatching) 1.Failure of heart due to massive transfusion. 2.Release of serotonin from platelets causes pulmonary edema. 3.Allergic reaction to donor's proteins producing rigors, skin rash or even anaphylactic shock. 4.Transmission of diseases like AIDS, Syphilis, infective hepatitis, malaria etc. 5.Febrile reaction. 6.Air embolism. 7. Tetany due to excess anticoagulant in blood. *Q. FUNCTIONS OF PLATELETS Platelets are non nucleated, round or oval disc shape cells present in blood (1.5 to 4 lakhs per cmm).

Their functions are: 1. Role in Vascular Spam:Activated Platelets release chemicals like serotonin, noradrenaline and thromboxane A2 which cause spasm of injured blood vessel and minimize blood loss. 2. Platelet plug formation: Contact of platelets with exposed collagen fibers activates them. They start swelling, develop many processes, become sticky and release chemicals like ADP which activated platelets then adhere to together forming a platelet plug that seals the opening in small capillaries caused by day to day activities. 3. Role in coagulation:-Platelet phospholipids and platelet factor III help in activation of factor X and also formation of prothrombin activator in intrinsic pathway of coagulation. 4. Stablization of Clot:- Platelets produce fibrin stabilizing factor(XIII)which forms cross linkages between adjacent fibrin threads and stabilizes the clot. 5. Clot retraction:- Processes of platelets attached to fibrin threads contract after 30 to 60 minutes causing the clot to be smaller and more firm with exudation of serum. 6.Growth of Endothelial cells:-Platelets secrete certain substances which promote growth of endothelial cells and repair of blood vessels. Applied Physiology:-decrease in the number of platelets below 50,000 per cmm produces a clinical condition called thrombocytopenic purpura characterized by multiple subcutaneous punctate haemorrhages and prolonged bleeding and clot retraction time. *Q. FUNCTIONS OF PLASMA PROTEINS: Plasma proteins include albumin(4 to 4.5 gm%)Globulins(1.5 to 3 gm%) Suggestions: facebook.com/asifpatel.ggmc

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22 consisting of alpha, beta and gamma globulins, Fibrinogen(0.3 to 0.4 gm%)and other proteins like prothrombin coagulation factors etc.

Functions: 1.Colloid osmotic pressure: Plasma proteins, especially albumin exert colloid osmotic pressure and promote reabsorption of water at venous end capillaries. They therefore play an important role in regulating tissue fluid formation and glomerular filtration. 2.Coagulation:Plasma proteins include many coagulation factors like prothrombin, fibrinogen etc. which when activated form blood clot and stop the bleeding. 3.Viscosity:-Plasma proteins, especially fibrinogen and globulin are responsible for viscosity of plasma and contribute to peripheral resistance. 4.Buffers:-Plasma proteins act as buffers and help in maintaining pH. 5.Transport:-Albumin transports bilirubin and hormones like thyroid hormones, Globulins transport cortisol(transcortin) hemoglobin(Haptoglobin), cholesterol & triglycerides (B lipoproteins), and metals like iron(transferrin)and copper(ceruloplasmin). 6.Defence function:-Immunoglobulins produced by plasma cells are gamma globulins which can attack bacteria and destroy them. Complement enzymes also have similar function. 7.Reserve of proteins:-Plasma proteins act as reservoir of proteins for cells. 8. Proteins like erythropoietin and colony stimulating factors stimulate erythropoiesis and leucopoiesis. 9. They transport small quantities of CO2 as carbaminoproteins. 10. Tissue repair. 11. Alpha 2 macroglobulin acts as anticoagulant by inhibiting thrombin. It also has antiplasmin activity. Applied Physiology:-Dietary deficiency of proteins or diseases of liver produce hypoproteinemia and edema.

Q. HEMOPHILIA:It is a condition characterized by prolongation of clotting time. There are 2 types of hemophilia1.Hemophilia A(classical):-forms 85% of hemophilia cases and is due to deficiency of coagulation factor VIII, i.e. Anti Hemophilic Globulin. Function of factor VIII:-In the intrinsic pathway of coagulation,factor VIII is essential along with factor IX, calcium ions and platelet phospholipids for activation of X which then forms prothrombin activator. Factor VIII is made up of 2 components a smaller component(mol wt 270,000)whose deficiency causes hemophilia and a larger component called Von Willebrand factor whose deficiency produces Von Willebrand disease. 2. Hemophilia B (Christmas disease):-Forms 15% of hemophilia cases and is due to deficiency of factor IX(Christmas factor or PTA)which is also essential for activation of factor X. It is a hereditary disorder due to presence of a defective gene on X chromosome which fails to cause synthesis of factor VIII or IX. Therefore the disease is seen in males while females act as carriers. Clinical Features: This condition is characterized by extensive and prolonged bleeding even after a mild trauma. Knee joint and elbow joint may be suffused with blood. Prolonged uncontrollable hemorrhage may cause death. Bleeding time is normal and clotting time is increased. Treatment:-Administration of purified factor VIII or IX prepared from fresh human plasma (cryoprecipitate) or plasma transfusion. *Q. PERNICIOUS ANAEMIA:-

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Is a maturation failure type of anemia that results from lack of absorption of vit B12 (Daily requirement 1 to 3 micrograms) Etiology:- In this condition the basic cause is atrophy of gastric mucosa probably of autoimmune origin. Therefore there is no secretion of Intrinsic factor from parietal cells a glycoprotein that is essential for protection and absorption of vit B12 in the intestine. Lack of intrinsic factor leads to failure of absorption of vit.B12 and its deficiency. Role of Vitamin B12:- It is essential for synthesis of DNA, in the process of maturation of cells in erythropoiesis. It converts deoxyurilate into deoxythymidilate in the synthesis of thymine phosphate and also acts methyl donor. In the absence of Vit B12:-DNA synthesis is affected but RNA formation and hemoglobin synthesis continues producing large abnormal cells in bone marrow called Megaloblasts. Peripheral blood:-Shows presence of large oval cells called macrocytes with increased hemoglobin content. These cells have thin membranes and they are fragile. Hemoglobin contents of blood is reduced, MCV is increased(upto 150 cubic microns)MCH is increased MCHC is normal. There is anisocytosis and poikilocytosis. It is a macrocytic normochromic anaemia. Clinical:-There are signs of anemia like extreme pallor, breathlessness, tachycardia etc. There may be other manifestations such as degeneration of dorsal columns of spinal cord (Subacute combined degeneration). Treatment:-Treated by injections of vit B12 at regular intervals and supplemented by folic acid tablets. Similar megaloblastic anemia is seen in other conditions like gastrectomy, sprue and fish tapeworm infestation. *Q. ERYTHROPOIETIN:Is a hormone produced by the kidneys and has stimulating effect on erythropoiesis. Chemistry:-It is glycoprotein in nature and has a mol.wt. of 34,000. Site of Production:-Some believe that erythropoietin is directly secreted by mesengial cells or by juxtaglomerular cells of renal glomeruli or by peritubular interstitial cells of kidney. Other believe that these cells produce a substance called Renal Erythropoietic Factor Which acts on a plasma protein called Erythropoietinogen to form Erythropoietin. Actions: 1)It acts on pleuripotent stem cells and promotes their conversion into cells of erythroid series. These stem cells are called erythropoietin sensitive stem cells. It also simulates mRNA synthesis in these cells. 2)Promotes conversion of CFU-E cells into proerythroblast cells and their maturation. 3)It stimulates synthesis of hemoglobin. New RBCs start appearing in circulation in 3-4 days. Stimulus for secretion:-Is the state of Oxygenation of the tissues i.e. hypoxia is the most potent stimulus for secretion of erythropoietin and thus regulates, erythropoiesis. Hypoxia may result from conditions like blood loss, anemia, congestive heart failure, chronic lung diseases or high altitude. Erythropoietin production is stimulated by hormones like thyroid hormones, cortisol and androgens. Clinical significance: Normal rate of erythropoiesis is maintained by circulating levels of erythropoietin. In chronic renal diseases or after nephrectomy, person develops anemia sometimes there is inappropriate erythropoietin secretion producing polycythemia. Q. ERYTHROCYTE SEDIMENTATION RATE(E.S.R):Definition:- E.S.R. is defined as the rate of sedimentation of RBCs when a sample of blood is mixed with suitable anticoagulant and suspended vertically in a tube. It is expressed in millimeters of clear supernatant plasma at the end of one hour. Sedimentation occurs because RBCs (specific gravity 1.090)are heavier than plasma. The process occurs in three stages. 1. Stage of Rouleaux formation in which RBCs pile up upon one another. Suggestions: facebook.com/asifpatel.ggmc

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24 2. Stage of sinking (sedimentation) and 3. Stage of packing. Normal Value:Males 0 to 9 mm and females 0 to 20 mm at the end of one hour. (Wintrobes method) Males 3 to 5 mm and females 5 to 7 mm at the end of one hour. (Westergrens Method)

Factors affecting E.S.R: 1. Rouleux formation increases E.S.R by increasing mass : volume ratio. 2. Fibrinogen and globulins increase E.S.R. In disease conditions, these and other proteins released by tissue damage increase the E.S.R. 3. Number of RBCs :-ESR is inversely proportional to number of RBC. 4.Albumin and lecithin retard Sedimentation and reduce E.S.R . 5.Cholestrol increases E.S.R. 6. Abnormal shape of RBCs retards E.S.R. 7.Rise in temperature increase E.S.R. Clinical significance:-1.Increase in E.S.R indicates presence of an organic disease in the body associated with tissue damage. 2.Prognostic Value:- Serial estimation of E.S.R at regular interval indicates progress or deterioration of patient’s condition. 3.It has no diagnostic value. Clinical:- it is increased in conditions like tuberculosis, syphilis, leprosy, acute infection, rheumatic fever, anemia etc.

*Q. ANTICOAGULANTS:Anticoagulants are the substances which delay or retard the process of coagulation. They include: 1.Heparin:It is a strongly negatively charged conjugated polysaccharide. Production:- In the body, it is produced by mast cells in liver and lungs and also by basophils in blood. Actions:- 1.It combines with Antithrombin III and forms a powerful Heparin Antithrombin III cofactor. This factor blocks the effect of thrombin on fibrinogen. It also inactivates thrombin that is bound to fibrin threads. 2.It removes other activated coagulation factors like IX, X, XI & XIII. 3.It also prevents formation of thrombin by opposing the action of activated factor X. Clinical:-Heparin is given by injection because it is destroyed in G.I.T .when given orally. It’s anticoagulant effect is seen immediately. 2.Oral Anticoagulants :-These are coumarin derivatives e.g. Warfarin or Dicoumarol. These drugs can be given orally because they are not destroyed in G.I. tract. Mechanism of action:- These drugs are naphthoguinone derivatives having structure similar to vitamin K. Therefore they compete with Vit. K for receptor sites on liver cells and reduce the synthesis of clotting factors like prothrombin, factors VII, IX and X(Competitive inhibition). Decreased synthesis of these factors retards the process of coagulation. These drugs have longer latent period of action because they reduce synthesis of clotting factors and do not have direct action on coagulation process .Prothrombin time and clotting time should be monitored in patients receiving anticoagulants. Clinical uses of Anticoagulants:1. In treatment of thromboembolic conditions like (a) Thrombophlebitis. (b) Pulmonary embolism. (c) Disseminated intravascular coagulation. 2. To prevent occurrence of coronary thrombosis. Suggestions: facebook.com/asifpatel.ggmc

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Q. PACKED CELL VOLUME (PCV):Definition:-It is the ratio of volume of cells in blood to the total volume of blood expressed as percentage. It is also called Hematocrit value. Normal value:- Males 42 to 45%. Females 38 to 42%. Measurement:-2 ml of venous blood is collected in double oxalate bulb and filled into wintrobe’s tube upto mark ‘10’. It is then centrifuged at 3000 rpm for 30 minutes. Centrifuging is repeated every 56 minutes till the cells are completely packed. Then the height of cell column is noted and expressed as percentage. Layers in PCV:-The centrifuged tube shows 4 layers from above downwards .They are 1.Layer of plasma. 2. Layer of WSCs and platelets (buffy coat) 3. Layer of deoxygenated RBCs. 4. Oxygenated RBCS. Clinical significance of PCV:1. It is a simple and accurate method to detect presence or absence of anemia or polycythemia. It falls in anaemia and rises in polycythemia. 2. It indicates viscosity of blood which is increased in conditions like burns, dehydration etc. 3. It is one of the blood indices and is useful in calculation of other indices like MCV and MCHC and helps in classification of anaemia. 4. Supernatant plasma in PCV tube also gives some information e.g. it is dark yellow in jaundice, red in hemolytic conditions etc. True cell volume :-Is the actual volume of cells excluding the plasma trapped between the cells during centrifugation. It is 96% of P.C.V. PCV of venous blood is slightly greater than arterial blood because of chloride shift.

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NERVE-MUSCLE PHYSIOLOGY

Chapter 3

*Q. What is Resting Membrane Potential? Explain its genesis. Resting Membrane Potential is the potential difference that exist across the membrane of an excitable cell in its resting state. Normal Value:-In case of large nerve fibers and muscle fibers it is -90 mv i.e. inside of the membrane is negative with respect to outside. Genesis of R.M.P: RMP basically results from accumulation of more negatively charge ions on the inner surface of cell membrane and more positive ions on its outer surface. This unequal distribution of charges results from. A)Diffusion Potentials created by conc. Difference of ions across the cell membrane:1.Role of K+ ions: Normally the conc. Of K+ in ICF is 140 meq/liter and in ECF, it is 4 meq/lit. Therefore k+ ions tend to diffuse out of the cell. At the same time, outward diffusion of K+ ions will create a negativity inside the cell which will oppose the outward movement of K+ ions. Thus a state of equilibrium will be reached in which there will be no net ionic flow across the membrane. The Potential developed at this stage is called ‘Equilibrium potential’ or ‘Nernst Potential ’for K+ ions. Its value depends upon conc. gradient and can be calculated by using Nernst equation as follows. Ek+ (mv)= RT/F Z X log K+ conc. Inside/conc. outside where R is gas constant, T absolute temperature, F is Faraday and z is valency of ion. (Simplified form E(K+)= ±61 log K+ conc. inside/K+ conc. outside) Equilibrium potential for K+ ions is -94 mv which is very close to RMP indicating that K+ diffusion potential contributes significantly to RMP. One of the reasons for this is greater permeability of membrane to K+ ions compared to Na+ ions. 2.Role of Na+ ions:-Concentration of Na+ ions in ECF is 142 meq/1 and in ICF only 14 meq/1. Therefore Na+ ions tend to diffuse into the cell. However, the resulting positivity in the cell will oppose the entry of more Na+ ions. Nernst potential for Na+ ions is +61 mv which is far away from RMP indicating that Na+ diffusion Potential contribution is very little towards RMP. 3.Role of Chloride ions:-Equilibrium potential for Cl ions is –70 mv, however their contribution to RMP is insignificant because of their passive diffusion secondary to movement of Na+ and K+ ions. Diffusion potential for K+ an Na+ together account for membrane potential of – 86 mv. B)Selective Permeability of cell membrane:-Resting cell membrane is 50 to 100 times more permeable to K+ ions due to K+ leak channels. Besides, the cell membrane is impermeable to certain negatively charged ions in the cell such as proteins, sulphates and organic phosphates. So they remain inside the cell and contribute to the negativity. The membrane potential which results from the sum total of above factors is given by Goldman’s constant field equation which consider the conc. difference of ions as well as their membrane permeability. Suggestions: facebook.com/asifpatel.ggmc

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C)Role of Na+ K+ pump:- It is a protein present in cell membrane which pumps 3 Na+ ions out of cell and 2 K+ ions into the cell. It contributes to RMP in 2 ways1.Indirectly,by maintaining conc. gradient of Na+ and K+ ions across cell membrane. 2.Directly,by acting as an electrogenic pump. It causes net loss of positive ions from cell and contributes -4 mv to RMP. Significance of RMP: 1. It forms the basis of action Potential which is necessary for impulse transmission. 2. A change in RMP of a receptor cell is called Receptor Potential essential for transmission of sensation. 3.Resting negativity also helps in absorption of positive ions like Na+ in renal epithelial cells.

*Q. Define Action Potential. Describe the electrical changes occurring in a cell membrane during action potential.

Definition: It is the membrane potential consisting of depolarization followed by repolarization when an adequate stimulus is given to an excitable cell. It consists of following phases: 1.Resting Stage:-Resting membrane potential is -90 mv. In this stage the activation gates of voltage gated Na+ channels and voltage gated K+ channels are closed, but inactivation gates of Na+ channels are open. 2.Phase of Depolarization: In this phase intracellular negativity decreases and may even become positive (reversal of potential). It results from sudden increase in permeability of membrane to Na+ ions. When an adequate stimulus is applied to the cell membrane, intracellular negativity starts decreasing and rapidly reaches a level of about –65 mv (threshold of depolarization). This decreased intracellular negativity acts as a stimulus for activation gates of voltage gated Na+ channels which open rapidly. Therefore Na+ ions flow into the cell decreasing the negativity further which opens still more voltage gated Na+ channels and this Positive Feedback Mechanism continues till all the Na+ channels are activated (Membrane activation). As a result, the permeability of the membrane to Na+ ions increases 500 to 5000 times. Therefore Na+ ions rush into the cell carrying positive charges and the membrane potential rapidly shoots to ‘O’ and may even become positive producing a spike in the record(Spike potential). In this phase, the inactivation gates of voltage gated Na+ channels are open while the activation gates of voltage gated K+ channels are closed. Suggestions: facebook.com/asifpatel.ggmc

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28 3.Phase of Repolarization :-In this, the membrane potential recovers and returns to its resting negativity. It results fromA)Inactivation of Na+ channels:-Within a fraction of millisecond after opening of activation gates, the inactivation gates of Na+ channels start closing. The stimulus for closure of inactivation gates is also decrease in intracellular negativity, but it occurs a fraction of millisecond later. Closure of inactivation gates stops. Na+ inflow terminates depolarization and initiates repolarization. B)Activation of K+ channels:-Decrease in intracellular negativity also opens the activation gates of voltage gated K+ channels but the process in slower and occurs a fraction of millisecond later (delayed activation). As a result there is increase in permeability of membrane to K+ ions, hence positively charged K+ ions diffuse out of the cell (from high conc. to low conc.) and the membrane potential returns towards resting value. 4)Negative After Potential:-Towards the end the process of repolarization becomes slower because some voltage gated K+ channels start closing. This is called Negative after potential. 5)Positive After Potential :-At the end of action potential, membrane potential becomes more negative (hyperpolarized)because some K+ channels remain open even after repolarization is complete, hence K+ ions continue to diffuse out. This phase is called positive after potential. Recharging of the membrane:- After the occurrence of action potential, the cell gains some Na+ ions and loses some K+ ions. But the Na+ pump present in cell membrane helps in restoration of ions. Significance:1.Action potential forms the basis of transmission of signals in neural and muscular tissue. 2.It is also the basis of refractory period. *Q. Describe the molecular basis of muscle contraction. Contraction of skeletal muscle involves 2 types of proteins – A. Contractile proteins called Actin and Myosin. B. Regulatory proteins called Tropomyosin and Troponin. MYOSIN MOLECULE :-

Each myosin molecule (mol. wt. 4,80,000)is made up of 6 polypeptide chains ; 2 heavy chains and 4 light chains . At one end, the heavy chains are coiled around each other forming a double helix or ’tail’. At the other end, the heavy chains project outwards and are folded at the tip to from a globular 'head'. Each head of myosin molecule also has (a) 2. Light chains, (b) ATP binding site and (c) ATPase activity. The projecting part of heavy chain called ‘arm’ which together with head forms 'crossbridge’ which is flexible at two points called 'hinges'. Myosin Filament :- About 200 such myosin molecules are organized to form myosin filament which is 1.6 microns in length and 12-15 nm in diameter .The tails of myosin molecules are bundled together to form body Suggestions: facebook.com/asifpatel.ggmc

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of myosin filament, while the cross bridges project outwards in either directions away from central part of myosin filament. Each successive pair of cross bridges is axially displaced by 120 degree from previous pair . ACTIN : Actin present in muscles is a globular protein called G actin (mol. Wt. 42000) such G actin molecules are Polymerized to form F actin strands. Two such F actin strands wind around each other to form actin filament which is one micron in length and 5-6 nm diameter .There are 13 G actin molecules in one revolution of F actin strand. There is one active site on each G actin molecule to which head of myosin molecules bind. Tropomyosin:-Is an elongated ribbon like molecule having length 40 nm and mol.wt.70,000. Many such tropomyosin molecules are polymerized to form tropomyosin strands which are situated in the groove between two F actin, strands loosely attached to them. In the resting state, tropomyosin strands physically cover the active sites on actin filament and prevent interaction between actin and myosin. Troponin:- Is a globular protein molecule attached to each tropomyosin molecule .It is made up of 3 sub unit: Troponin T which binds with tropomyosin, troponin I which has strong affinity for actin and troponin C with 4 calcium ions. MECHANISM OF CONTRACTION :-

contraction results from sliding of actin filaments over the myosin filaments .

Muscle

1.Arrival of impulse in muscle fiber causes release of Ca+ ions from L tubules. 2.Ca+ ions combine with troponin C on actin filament. 3.Troponin – tropomyosin complex is displaced deeper into the groove exposing active sites on actin filament. 4.Heads of myosin filaments attach to active site . 5.Attachment of head causes change in intramolecular force leading to tilting of head towards the arm and thus the actin filament is dragged towards center of myosin filament (power stroke) 6.Tilting of head exposes ATP binding site to which ATP binds so the head of myosin gets detached from active site. 7.Detached head then splits ATP and the released energy cocks the head back to perpendicular position .(Recovery Stroke). 8.It then binds with actin molecule further down the actin filament and the process in repeated . Thus the heads of myosin filaments walk along the actin filaments. Hence this mechanism is called ‘walk along theory ‘ or ‘Retchet Theory’ of muscle contraction. Suggestions: facebook.com/asifpatel.ggmc

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*Q. Describe the process of excitation – contraction coupling in a skeletal muscle fiber . Definition: The process by which action potential in a muscle initiates its contraction is known as excitation contraction coupling and includes all the events from excitation of muscle to the release of Ca+ ions in sarcoplasm which ultimately causes muscle contraction. Sarcotubular system:-Forms the basis of excitation contraction coupling. It consist of 1.Transverse or T tubules :-These are the tubular extensions arising from sarcolemma and extending deeper into the muscle fibers .They are situated transversally (Across) and extend from one side of the muscle to the other, surrounding the myofibrils on their way forming a grid network in a transverse plane through which myofibrils pass. These tubules contain E.C.F. and there most important function is to carry the excitation into deeper parts of muscle fiber. There are two such T tubules traversing each sarcomere . 2.Longitudinal L tubules:-These are parts of sarcoplasmic (Endoplasmic)Reticulum and are arranged longitudinally situated between the myofibrils. At either ends they have dilatations called ‘Terminal cisternae’. There are small projections cord junctional feet arising from terminal cisternae and projecting towards T tubules. The L Tubules store large quantity Ca ions and protein called cal-sequestrin facilitates the storage. L tubules also contains voltage gated Ca ++ channels and calcium pumps. Each inward extending T tubules is sandwiched between two terminal cisternae on either side forming a complex called triad. Sequence of events:-

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1.Neuromuscular transmission initiates action potential in muscle fiber which spreads along the sarcolemma. 2.It then dips into the muscle fiber through T tubules. 3.At the triad, the current spreads into the terminal cisternae of T tubules through junctional feet causing its depolarization. 4.This opens Ca+ channels in terminal cisternae and Ca+ ions are released into sarcoplasm .Released Ca+ ions then initiate contraction. 5.In the resting state of muscle the troponin – tropomyosin, complex covers the active sites of actin filament and prevents interaction between actin and myosin. 6.The Ca+ ions that are released from L tubules then combine with troponin C on actin filament.(Points 3 to 8)from earlier question. After excitation is over, the Ca+ pump present in L tubules pumps Ca+ ions from the sarcoplasm into the L tubules and initiates relaxation. Thus the main factor that couples excitation with contraction is the Ca+ ions. *Q. Describe the process of neuromuscular transmission.

Transmission of excitation from nerve to the muscle is called neuromuscular transmission. FUNCTIONAL ANATOMY OF NM JUNCTION:

As the branch of motor axon approaches the muscle fibre, it loses myelin sheath and divides to form 3 to 4 small branches called and feet or terminal bouttons which have knob like expansions at the tip. These axon terminal contain: 1.Synaptic vesicles containing the neurotransmitter(mostly Acetyl Choline). 2. Large number of mitochondria which provide energy for synthesis of acetylcholine. 3.Linearly arranged dense bars and 4.Voltage gated Ca+ channels situated close to dense bars which open on depolarization. The axon terminals invaginate into the muscle membrane forming a groove called synaptic gutter or trough. The region where axon terminals end on muscle membrane is called Motor End Plate and is covered by schwann cells. Suggestions: facebook.com/asifpatel.ggmc

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32 There is a gap of 20 to 30 nm between the axon terminal and muscle membrane called Neuromuscular cleft, which is filled with extracellular fluid. It contains spongy reticular fibers called basal lamina to which is attached the enzyme, Acetyl cholinesterase. The portion of muscle membrane under the axon terminal is called post junctional membrane. It is thrown into a number of folds called subneural clefts which increase its surface area. The post junctional membrane contains receptors for acetylcholine which are concentrated in the neck region of subneural clefts. These receptors are ACh gated tubular channels consisting of 5 subunits having a diameter of 0.65 nm and lined by negative charge. Transmission of excitation:-

1.Arrival of action potential at the axon terminal causes depolarization of its membrane and opening of voltage gated Ca+ channels. 2. Therefore Ca+ ions diffuse into axon terminal from ECF. 3.These Ca+ ions cause migration and fusion of Ach vesicles with axon terminal membrane near dense bars. 4. The area of fusion breaks down and ACh is released by exocytosis into N.M. cleft. 5. Ach then diffuse through the cleft and combine with Ach receptors on post-junctional membrane. Combination of ACh (ligand)opens these ligand gated channels. As a results Na+ ions diffuse from ECF into the muscle membrane and decrease its resting negativity (-85 to -90 mv). 6. This local transient depolarization of post junctional membrane is called End Plate Potential. 7.When EPP reaches a threshold level (about – 55 mv). An action potential is elicited in the muscle membrane which travels along either sides of NM junction dips into the muscle through T tubules and elicits muscle contraction. Within a few milliseconds after its release, most of Ach is destroyed by cholinesterase enzyme and some diffuses out into ECF. Safety Factor: Normally with each impulse in the nerve, the amount of Ach released is more than sufficient to elicit an action potential in the muscle, thus ensuring neuromuscular transmission for each impulse. Applied Physiology:1. In Myasthenia gravis, there is failure of NM transmission due to damage to Ach receptors of autoimmune nature. 2. Drugs like curare block NM transmission by causing competitive inhibition of Ach and are useful as muscle relaxants. *Q. MOTOR UNIT Definition :-It is a unit consisting of motor neuron in the spinal cord, its axon and the muscle fibers innervated by that neuron. Properties: 1)It is the smallest part of a muscle that can contract. 2)The muscle fibers in a motor unit are not grouped together in a muscle but are spread out in microbundles of 3 to 15 muscle fibers and are found in muscle with fine degree of control e.g. laryngeal or ocular muscles. Such motor units are called small motor units. They are more excitable and their muscle fibers have oxidative metabolism. On the other hand, some motor units contain 200 to 300(or even more)muscle fibers. Such large motor units are presents in postural muscles. 4)All or None law:-Motor units obey all or none law that is when the axon of a motor units is stimulated with adequate stimulus all fibers in that motor unit contract, however if the stimulus is inadequate not a single fiber contracts. Suggestions: facebook.com/asifpatel.ggmc

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5)Recruitment of motor units(Size principle)- in case of a whole muscle, when a weak stimulus is applied only small motor units which are more excitable contract producing weak contraction .As the strength of stimulus is increased, larger and larger motor units contract producing stronger contraction .This is known as size principle and the recruitment of motor units is called Multiple fiber quantal summation.

*Q. MYASTHENTIA GRAVIS It is a disease resulting from failure of neuromuscular transmission. It occurs in about 1 in 20,000 persons and is seen more commonly in females than in males. The peak age at which it occurs is about 30 years. Cause:-In this condition, there is destruction of acetyl choline receptors(Ach gated channels) on the post junctional membrane by antibodies formed in blood. Hence it is an autoimmune disease. Therefore even though sufficient acetyl choline is released by the nerve endings, it cannot produce an end plate potential that will reach threshold level and produce action potential in muscle membrane. Thus neuromuscular transmission is blocked. Histologically the NM junction shows decrease in the number of subneural clefts and widening of neuromuscular (synaptic)cleft.

Clinical features:-There is extreme weakness and fatigability(Myasthenia-muscle weakness, gravis - grave).There is drooping of eyelids, dysphagia, nasal regurgitation of food(due to paralysis of palatal muscles) and inability to carry out sustained movements. In severe cases there may be paralysis of muscles including the muscles of respiration which can be fatal. EMG shows small amplitude waves. Physiological basis of treatment: 1)Anticholinesterases like neostigmine and physostigmine. These drugs inactivate the enzyme acetyl cholinesterase so that large amount of ACh accumulates at the post junctional membrane and stimulates sufficient number of existing Ach receptors to produce end plate potential and action potential, leading to NM transmission . 2.Drugs like cortisol are used in high doses to suppress formation of autoantibodies. 3.Thymectomy may help to suppress antibody formation, because some cases of myasthenia are associated with thymic hyperplasia.

*Q. Wallerian Degeneration: Definition: Are the degenerative changes taking place in the distal part of nerve fiber when there is cutting injury to the nerve. The changes occurring in the peripheral cut portion are : 1. The axis cylinder swells and breaks up into short segments. 2. There is disintegration of myelin sheath. The lipids are broken down by the Schwann cells into sphingomyelin, cholesterol and fatty acids and appear as fat droplets. 3. There is rapid multiplication of Schwann cells in about 4-9 days. 4. Nerve sheath or neurilemma remains intact. Phagocytes (tissue macrophages) enter the neurilemma tube and remove broken down pieces of axis cylinder and lipid droplets by phagocytosis. 5. Schwann cells proliferate and completely fill up neurilemmal tube. Suggestions: facebook.com/asifpatel.ggmc

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34 These changes start within 24 hours of injury and are complete by 3-4 weeks. If the distance between cut end is less, sprouts arising from proximal axon stump can enter neurilemmal tube and regeneration is possible. Some changes also occur in proximal stump and cell body of neuron. The proximal cut end shows degeneration of nerve fiber up to first node of Ranvier or up to collateral branch of axon cells body of neuron shows swelling and chromatolysis (disappearance of Nissels granules). All changes were first described by Waller in 1862. *Q. ELECTROMYOGRAM (EMG) Definition:-EMG is a record of Electrical activity of the contracting muscles. Recording:-EMG can be recorded by using instruments like physiograph or Cathode ray oscilloscope. EMG Record:-When the muscle are in resting state no electrical activity is recorded. A voluntary contraction results in production of motor unit potentials of 1 mv lasting for 5 msec. A weak voluntary contraction shows small amplitude low frequency potential changes, but as the force of contraction increases due to recruitment of more motor units, the amplitude and frequency of EMG waves goes on increasing because of summation of electrical activity. The frequency of EMG waves ranges from 20 – 200 cycles/sec. Clinical Use of EMG:- EMG is useful in diagnosis of lower motor neuron diseases, peripheral nerve injuries, neuritis and myasthenia gravis. A totally paralyzed muscle will not show fasciculations and fibrillations which are recorded as weak (0.05 mv) periodic potentials.

*Q. RIGOR MORTIS:Definition:-Few hours after death, the muscle of the body become stiff and rigid. This state of contracture of muscles is called Rigor Mortis. Cause:-Normally, relaxation of muscle is an active process and result from pumping out of calcium, ions from sarcoplasm into the L Tubules. After death ATP synthesis stops, hence no ATP is available to pump out calcium ions. Therefore actin and myosin remain bound together and cannot dissociate . Timing and Sequence:It begins in about 2 - 3 hours after death and is complete in 12 hours . Sequence of muscles involved: first the muscles of lower jaw, then face, neck, thorax, abdomen, upper limbs and lastly the muscles of the lower limbs . Disappearance:Rigor mortis disappears in 24 - 36 hours after death due to autolysis of muscle tissue .Sequence of disappearance is same as that of appearance of rigor mortis. Changes in the muscles:1.Muscles become stiff. 2.Decrease in length. 3.Loss of translucency. 4.Glycogen disappears. 5. pH becomes acidic . Factors affecting rigor mortis :1.Exercise prior to death hastens the onset of rigor mortis. 2.Temprature: Increased temperature (hot climate) causes early appearance of rigor mortis . 3. Arsenic also has ten rigor mortis . Clinical significance: - Rigor mortis is of medicolegal importance and helps to fix the time of death of a person. *Q. SALTATORY CONDUCTION :Definition:- Saltatory condition is the mode of transmission of an impulse in which the impulse jumps from one node of Ranvier to the next . it is seen in case of myelinated nerve fibers .

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Mechanism of transmission :The myelinated nerves are covered by myelin sheath deposited by Schwann Cells . It contains the lipid . Sphingomyelin, which acts as insulator and prevents the flow of ions across the membrane . The myelin sheath is interrupted at flow of ions between axoplasm and E.C.F. when the nerve fibre is stimulated, there is depolarization of node of Ranvier under the electrodes. The Na+ ions that defuse into the axon at this site flow to the net node of Ranvier through the axoplasm and decrease its negativity to the thresh old value eliciting action potential . Thus action potential is generated at successive notes of Ranvier and impulse jumps from one node to the next because intermediate portion of axon is insulated. Significance of saltatory conduction :1. It increase the velocity of transmission of an impulse 5-250 times. Therefore conduction is faster in myelinated than in un myelinated fibres . 2. It conserves the energy for the axon because ions flow only at the nodes of Ranvier, therefore less energy is required to reestablish concentrations of Na+ and K+ ions across the membrane. 3. The process of repolarisation becomes faster ( permitting transmission of more impulses) because very few ions are transferred out of fibres during depolarization.

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CARDIOVASCULAR SYSTEM

Chapter 4

*Q. Define Cardiac Cycle. Describe the events in Cardiac Cycle.

(Wiggers' diagram) Definition: Cyclical repetition of various mechanical changes taking place in the heart from beat to beat is known as Cardiac Cycle. Duration : Normal duration of Cardiac cycle is about 0.8 seconds (if heart rate 75/min) and is inversely proportional to the heart rate mechanical events taking place in the heart are secondary to electrical events . Events are classified into: A) ATRIAL EVENTS:- 1. Atrial Systole :- is the phase of atrial contraction. (Duration- 0.1 sec). contraction first starts in right atrium because pacemaker S.A. node is situated here . The first phase of atrial contraction is strong and called Dynamic Phase (0.05sec). Contraction becomes weaker in later part, called Adynamic phase (0.05sec). Atria act as primer pumps and atrial systole is responsible for 25% of ventricular filling . 2. Atrial diastole :- is the phase of atrial relaxation, (duration -0.7 sec.). For first 0.4 sec, AV valves remain closed and blood accumulates in atria. When they open, blood rushes into the ventricles. B) VENTRIVULAR EVENTS:1)Ventricular Systole:- Is the phase of ventricular contraction. Duration - 0.3 sec. Begins at the end of atrial systole because cardiac impulse is delayed at the AV node. As ventricular contraction begins, ventricular pressure exceeds atrial pressure causing closure of AV valves and production of First Heart Sound. There are 3 phases of ventricular systole:a)Isovolumetric contraction phase: Lasts from closure of AV valves to opening of semilunar valve. In this phase, ventricles are contracting as closed chambers with both AV and SL valves closed. Blood does not leave the ventricles and ventricular pressure rises sharply.(duration=0.05 sec) b) Rapid Ejection phase: As ventricular pressure exceeds that in aorta and pulmonary artery, SL valves open and blood is ejected into those vessels. Force of ventricular contraction is strong and 80 % blood is ejected in this phase (Duration-0.11sec.) Suggestions: facebook.com/asifpatel.ggmc

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c) Reduced Ejection phase: Force of contraction becomes weaker. 20% ejection occurs in this phase( Duration 0.14 sec). Ventricular pressure starts falling. 2) Ventricular diastole: It is the phase of relaxation (duration=0.5 sec) Divided into 5 phases a) Protodiastole: Extends from beginning of ventricular relaxation to closure of SL valves( Duration=0.04). Fall of ventricular pressure below that in aorta and pulmonary artery causes closure of SL valves and production of second heart sound at the end of this phase. b) Isovolumetric relaxation phase: In this phase both AV and SL valves are closed and ventricles relaxed as close chambers . There is sharp fall in ventricular pressure (Duration= 0.06sec). c) First rapid filling phase: Ventricular pressure falls below atrial pressure. Hence AV valves open and blood accumulated in atria gushes into the ventricles producing 3rd heart sound. This phase accounts for 70% of ventricular filling (Duration=0.11) d) Diastasis or slow inflow phase:- Both atria and ventricles are relaxing with AV valves open. Blood entering the atria from great veins flows into ventricles . Rate of blood flow is less and accounts for 10% of filling (Duration 0.19 sec.) e) Last rapid filling phase:- Corresponds to atrial systole with rush of blood into the ventricles causing fourth heart sound.(Duration-0.1 sec).At the end of this phase, next ventricular systole begins and the cycle is repeated. Applied Physiology:- 1.Clinically, the duration between the first and the second heart sound is considered as systole and that between second and first as diastole. 2. When heart rate increases, duration of diastole (esp. diastasis) is reduced to a greater extent than systole. *Q. Describe the pressure and volume changes taking place in the ventricles during cardiac cycle. Cardiac cycle is the cyclical repetition of various mechanical events taking place in the heart from beat to beat.

Ventricular pressure changes:1. Isovolumetric contraction phase:- In this phase, ventricles are contracting as closed chambers with both AV and SL valves closed. Therefore there is a sharp rise in ventricular pressure(80 mm Hg) in aorta and rt. Ventricular pressure exceeds that in pulmonary artery(8 mm Hg) leading to opening of SL valves. 2. Rapid ejection phase:-Ventricular pressure continues to rise because the force of ventricular contraction exceeds the rate of outflow of blood. It reaches a peak value of 120 mm Hg for left ventricle and 25 mm Hg for right ventricle. In this phase ventricular pressure remains slightly more than that in aorta and pulmonary artery. 3. Reduced Ejection phase:- Ventricular pressure starts falling because rate of outflow exceeds force of contraction. Ventricular pressure remains slightly below that in aorta or pulmonary artery, but blood continues to flow because of momentum. 4. Protodiastolic phase:- Pressure continues to fall because of onset of ventricular relaxation. 5. Isovolumetric Relaxation phase:- In this phase, there is sharp fall in ventricular pressure since ventricles are relaxing with both AV and SL valves closed. At the end of this phase, pressure falls below that in atria(4 to 6 mm Hg)and AV valves open. 6. First Rapid Filling phase:-Ventricular pressure continues to fall but at a slower rate because the rate of relaxation exceeds the rate of inflow of blood. 7. Diastasis:-Pressure rises slowly because of the continuous inflow of blood. 8. Last Rapid Filling phase:-Atrial Contraction forces the blood into the ventricles and causes a small rise in ventricular pressure. Suggestions: facebook.com/asifpatel.ggmc

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38 Applied physiology:-In aortic stenosis, there is hypertrophy of left ventricle producing a greater rise in pressure during systole. Ventricular volume changes:At the end of diastole, the volume of blood in ventricles is about 125 to130 ml. This is called End Diastolic Volume. In rapid ejection phase, blood is ejected from the ventricles into the aorta and pulmonary artery and ventricular volume decreases sharply. 80% of stroke volume is ejected in this phase. In reduced ejection phase, volume continues to decrease but at a slower rate because the force of contraction is less. At the end of ejection phase, the volume of blood in ventricles is 55-60 ml. This is known as End Systolic Volume. Normally, about 70ml of blood is ejected by each ventricle in one contraction out of 125 to 130 ml. This ratio is called ejection fraction which has a normal value of 65%.In protodiastole and isometric relaxation phase, there is no change in ventricular volume. In first rapid filling phase there is sudden increase in Ventricular volume due to flow of blood from atria. In last rapid filling phase, there is further increase in volume due to forcing of blood from atria to ventricles during atrial systole. Applied physiology:-Ventricular volume will be changed in conditions like dilatations of ventricles or constrictive pericarditis. *Q. Describe the Origin and spread of Cardiac impulse:Cardiac impulse is the self propogatory wave of electrochemical changes travelling along the conducting tissue of the heart leading to its excitation.

Origin:The cardiac impulse is originated in the Sino atrial(SA) node in human being. The rate of impulse generation by SA node is maximum, hence it acts as pacemaker. It is situated in the superolateral wall of right atrium just below the opening of superior vena cava and measures 15mmx3x1mm. It contains 2 types of cells: 1. Small round cells called P cells which initiates the impulse and 2. Slender elongated transitional cells. The ability of SA nodal cells to initiate the impulse is called automaticity which is due to its characteristic membrane potential called Pacemaker Potential. The RMP of SA nodal cells is less (-55 to -60 mv). Moreover it is not a steady potential, but in between the action potentials (phase 4), it shows gradual decrease in negativity to the threshold level (-40 mv) eliciting next action potential. This slope is called slow diastolic depolarization and it is due to 1.Natural leakiness of the membrane to Na+ ions which enter the cells through leak channels and decrease the negativity. 2. Decrease in K+ conductance of membrane after repolarization. 3.Movement of calcium ions (Ca+ current)into the cell. When the threshold potential is reached, there is opening up of slow Ca+ - Na+ channels leading to depolarization (+20 mv)followed by repolarization due to opening of K+ channels. Suggestions: facebook.com/asifpatel.ggmc

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39 Spread of Cardiac impulse through the conducting tissue of the heart:-

Impulse initiated at the SA node spread over right and left atria in a concentric manner at a velocity of 0.3 m/s Anterior interatrial band also carries impulse from right to left Atrium. Transmission of impulse from SA node to AV node takes place through anterior, middle and posterior internodal pathways (1 m/s) The atrio-Ventricular (AV)node is situated posteriorly on right side of interatrial septum near opening of coronary sinus. From SA node, the impulse reaches AV node in 0.04 Sec, but it is delayed at the AV node for 0.1 Sec. This is called Nodal delay and is due to slow conduction (0.02 to 0.05 m/s) in transitional and nodal fibers. The nodal delay 1)allows the atria contract before the ventricles begin contracting and 2)Protects the ventricle from excessive impulses coming from atria in conditions like atrial flutter. From the AV node, cardiac impulse enters the AV bundle (of His) which is the only conducting tissue between atria and ventricles. It passes through the fibrous ring at the atrio ventricular junction, passes subendocardially down the right side of interventricular septum and divides into right and left bundle branch. The left bundle branch divides into anterior and posterior fascicles on reaching the ventricular musculature. These bundle branches divide to form purkinje fibers which form an extensive network emerging with muscle fibers. The Purkinje fibers have high conduction velocity (1.5 m/s to 4 m/s) and ensure simultaneous excitation of all ventricular musculature essential for effective pumping. The impulse is ultimately transmitted through the ventricular muscle fibers at a slower velocity (0.3 to 0.5 m/s) from endocardial to epicardial side.

Applied physiology: 1.Impulse generation by structures other than SA node produce ectopic beats. 2. Failure of transmission of impulse along the conducting system leads to heart blocks.

*Q. Describe a normal Electrocardiogram and the information obtained from it:Electrocardiogram (ECG) is record of electrical changes taking place in the heart during cardiac by the electrodes placed on the surface of the body. It is the algebraic sum of electrical currents flowing in the heart due to formation of dipoles and transmitted to the surface of the body by the fluids which act as volume conductor. The instrument used for recording ECG is called Electrocardiograph. The normal (Standard limb lead II) ECG shows 5 waves, P, Q, R, S and T of which P, R and T are positive and Q and S are negative waves.

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P wave:-Is the first positive wave with rounded or pointed top. Duration - 0.1 sec. Voltage - 0.1 to 0.3 mv.It is due to depolarization of atria. A normal P wave indicates that impulse is arising from SA node.

QRS Complex:-Represents ventricular depolarization .Duration - 0.08 to 0.1 sec. Voltage - 1.0 to 1.2 mv. Q wave is small negative wave representing depolarization of left side of septum causing current to flow from left to right. It is normally absent in V(1) and V(2) leads. R wave is the positive wave after P. It is conspicuous and tall in lead II and in V(4) and V(5). It represents depolarization of major part of ventricles. S wave is a negative wave following R. It is due to depolarization of posterior based regions. T wave: It is a broad, rounded, positive wave coming after QRS complex. It is due to repolarization of ventricles. Duration - 0.27 Sec. Voltage - 0.2 to 0.4 mv. It is recorded as positive inspite of being a repolarization wave because repolarization occurs in a direction (epicardium to endocardium) opposite to that of depolarization .Normally it is negative in lead aV(R). U wave: a small positive wave, sometimes seen, following T wave and is due to slow repolarization of papillary muscles. Intervals: 1.PQ(PR) interval: time interval from beginning of P wave to beginning of ORS complex. Normal duration 0.13 to 0.16 Sec. It indicates time taken by the impulse to spread from SA node to AV bundle inclusive of nodal delay. 2.QT interval:-From beginning of Q wave to the end of T wave. Indicates the taken for ventricular depolarization and repolarization. Normal duration -0.35 to 0.4 Sec. 3.RR Interval:-From peak of one R wave to that of next. Indicates duration of cardiac cycle and heart rate. Normally 0.8 Sec. 4.TP interval:-From end of T wave to beginning of next P wave. Indicates period of heart. Segments:1)PR Segment:-Is the isoelectric Segment from end of P wave to onset of QRS complex. It is the period between atrial and ventricular depolarization. 2)ST Segment:- Isoelectric Segment from end of S wave (J point) to the onset of T wave. It is the period between completion of ventricular depolarization and beginning of repolarization.

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Clinical abnormalities:P wave:-Tall in atrial hypertrophy, inverted in AV nodal rhythm, absent in atrial fibrillation QRS complex becomes wider in bundle branch block. Tall R wave in leads V(5) and V(6) and deep S waves in V(1) and V(2) indicate left ventricular hypertrophy. Prolongation of PR interval more than 0.2 Sec indicates heart block. GGMC MUMBAI

41 T wave abnormalities in size, shape indicate myocardial hypoxia. It is inverted in myocardial ischemia and infarction due to delayed repolarization of damaged muscle fibers. Shift of ST segment also occurs in old infarction. *Q. DESCRIBE THE ROLE OF BARORECEPTORS IN REGULATION OF MEAN ARTERIAL BLOOD PRESSURE:Definition:- Baroreceptors are stretch receptors sensitive to change in arterial blood pressure. Nature and situation:-

They are extensively branched, spray type nerve endings situated in tunica adventitia of blood vessels. They are present throughout the vascular tree but concentrated in two regions. 1.Carotid sinus 2.Aortic arch. Afferent pathways: Afferent impulses from carotid sinus baroreceptors are carried through sinus (Herrings) nerve and then through the glossopharyngeal nerve while those from aortic arch are carried through aortic nerve and then through vagus. Most of these afferent fibers terminate in Nucleus of Tractus solitarius from which inhibitory interneurons project to pressor (C1) area of vasomotor Centre. Some fibers terminate in cardioinhibitory (nucleus ambiguus of vagus) Centre. Regulation of arterial pressure by baroreceptors(Sino-aortic reflex or Marey's reflex):

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When there is increase in mean atrial pressure, Sinoaortic baroreceptors are stimulated and impulses are carried through the sinoaortic nerves to 1) The pressure area of VMC causing its inhibition, hence the vasomotor tone decreases and there is peripheral vasodilatation. In addition, sympathetic discharge to the heart is also reduced decreasing the rate and force of contraction. 2) Cardioinhibitory area causing its stimulation, hence there is increase in vagal tone leading to decrease in heart rate and force of contraction. All these factors decrease arterial pressure back to normal. When arterial pressure falls, the resting baroreceptor discharge is reduced. Therefore inhibitory influence on vasomotor centre as well as excitatory influence on cardioinhibitory centre are removed leading to peripheral vasoconstriction, increase in heart rate and force of contraction thereby increasing arterial pressure back to normal. This reflex regulation of arterial pressure is called Sino-aortic(Marey's)reflex and the sino-aortic nerves are called buffer nerves. Response of baroreceptors:-1.They respond in the pressure range from 60 mm Hg to 180 mm Hg. 2.Response is prompt. 3.Their sensitivity (I/P) is maximum at mean arterial pressure i.e. 100 mm Hg. 4. They respond more to changing pressure than a steady rise in pressure. Importance of Baroreceptor mechanism:-It is the most important neural mechanism for immediate moment to moment control of arterial mechanism for immediate moment to moment control of arterial pressure in daily activities like change of posture, exercise etc. Ineffectiveness of baroreceptors:- Baroreceptors are not useful in long term regulation of arterial pressure because they get adapted to the changed pressure in 1 to 2 days. They are also ineffective when arterial pressure falls below 60 mmHg. Applied Physiology:-1.In clinical hypertension baroreceptors are reset at a higher value of arterial pressure. 2.Pressure on carotid sinus in the neck causes strong stimulation of baroreceptors leading to hypotension and fainting (Carotid sinus syncope). Suggestions: facebook.com/asifpatel.ggmc

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43 *Q. DESCRIBE THE HORMONAL MECHANISM REGULATING ARTERIAL PRESSURE: Hormonal Mechanism involved in regulation of blood pressure are classified into: A)Rapidly acting mechanism:- which act within few seconds to minutes. 1. Epinephrine-Norepinephrine Vasoconstrictor mechanism:-Fall in arterial pressure activates baroreceptors leading to increased sympathetic discharge throughout the body including adrenal medulla. Thus large amounts of epinephrine and norepinephrine are released into the circulation. They act on arteriolar smooth muscle causing peripheral vasoconstriction. They exert positive inotropic and chronotropic effects on heart. They also cause venoconstriction. All these effects increase B.P.

2.Vasopressin (ADH)Vasoconstrictor mechanism:- Sudden fall in arterial pressure will decrease the discharge from baroreceptors (and left atrial receptors) which, normally, has inhibitory effect on release of vasopressin from supraoptic neurons of hypothalamus. Due to lack of inhibition, large quantities of vasopressin are released which is very potent vasoconstrictor leading to increase in peripheral resistance and arterial pressure. B)Intermediate acting mechanism (few minutes to few hours) 3.Renin - Angiotensin II vasoconstrictor mechanism:Fall in arterial pressure decrease renal perfusion pressure and also increases sympathetic discharge to the kidneys. Both these factors bring about release of Renin from J.G. cells of kidney. Renin then acts on plasma protein Angiotensinogen to from Angiotensin I which is converted to Angiotensin II by converting enzyme in lungs. Angiotensin II is also very potent vasoconstrictor and raises arterial pressure.

C)Long term hormonal mechanism:- Acts in hours to days. They regulate arterial pressure by regulating E.C.F volume. 4.Fluid retention by Angiotensin II:- Constriction of renal arterioles by Angiotensin II decreases G.F.R and causes retention of Na+ and H2O raising the E.C.F volume and blood pressure. Angiotensin II also stimulates thirst centre and increases water intake. 5.Aldosterone:-Angiotensin II stimulates secretion of aldosterone from adrenal cortex, which then acts on distal and collecting tubules and increases reabsorption of Na+ and water thereby increasing ECF volume and blood pressure. 6.Anti Diuretic action of ADH (Vasopressin):ADH released by fall in atrial pressure or by action of Angiotensin II exerts long term actions also. It acts on collecting ducts and increases their permeability to water thus allowing reabsorption of more water and increase in ECF volume. 7.Atrial Natriuretic Peptide:-This hormone is released from atrial myocytes in response to increased distension of atria. Then blood volume (and hence blood pressure)rises, the hormone is secreted and acts on kidneys causing increased excretion of Na+ and water. It thus reduces ECF volume and B.P Other hormones like thyroxine, glucocorticoids and prostaglandins also increase blood pressure. Applied Physiology:-Hypersecretion of epinephrine (pheochromocytoma), of (hyperaldosteronism)of renin by renin secreting tumors, are all associated with hypertension.

aldosterone

*Q. DEFINE CARDIAC OUTPUT. DESCRIBE THE FACTORS MAINTAINING CARDIAC OUTPUT. Definition:-Cardiac output is the volume of blood pumped out by the heart(left ventricle)into the systemic circulation in one minute. It is also called minute volume. Normal value:- 5 to 5.6 Lit/min. Factors maintaining cardiac output:

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44 Cardiac output=Stroke volume x heart rate.

I. Venous Return or Preload:-It is the quantity of blood returning to the heart per minute. Normally upto a certain limit, whatever quantity of blood returns to heart, is pumped out by the heart into circulation. Therefore, when venous return increases, cardiac output also increases. Thus heart plays a permissive role upto a venous return of 13 lit/min in unstimulated condition. Increase in venous return increases cardiac output by 3 mechanism: 1.By increasing end diastolic fiber length. 2. by local stretching of S.A node. 3.by initiating Bainbridge reflex. Venous return, in turn, depends on: 1. Degree of dilatation of peripheral vessels: Which depends on rate of tissue metabolism. Thus the sum total of tissue blood flows controls venous return and cardiac output. 2. Blood Volume:-decrease in blood volume decreases venous return. 3.Increased activity of respiratory pump, increases venous return. 4.Activity of skeletal muscle pump: increases VR 5. Mean Systemic filling pressure(normally 7 mm Hg)provides pressure gradient for flow of blood to heart. 6. Gravity-Change of posture from lying to standing decreases VR. 7.Venomotor tone: Venoconstriction increases V.R. 8.Vis a fronte:-suction force created by strong ventricular contraction facilitates V.R. 9.Contraction of abdominal muscles compresses venous reservoirs and increase V.R. II. MYOCARDIAL CONTRACTILITY:- decides the stroke volume. It depends on: 1. Initial length of muscle fiber:(End diastolic volume):-Within physiological limits, greater the initial length of muscle fibers, stronger is the force of contraction. This is called Frank-Starlings law of heart which explains change in cardiac output in accordance with venous return.(Heterometric regulation). 2. Duration of diastole:- Decrease in duration of diastole(when there is increase in heart rate)decreases contractility of heart by a)reducing ventricular filling b)reducing coronary flow which mainly occures in diastole. 3. Degree of sympathetic stimulation and level of circulating Catecholamines:- These factors exert positive inotropic effect on heart due to stimulation of beta-1 receptors and increased cardiac output. Parasympathetic stimulation has opposite effects. These effects on contractility are independent of length(Homometric regulation) 4. Drugs like digitalis increase the contractility while conditions like hypoxia and acidosis decrease the contractility. III.HEART RATE:- Moderate increase in heart rate(about 120-130/min in unstimulated heart and about 170/min with sympathetic stimulation)increases cardiac output because diastolic filling is not significantly affected and the product of stroke volume and heart rate increases, but at higher rate stroke volume decreases to a greater extent and cardiac output falls. Heart rate increases during symp. stimulation by release of adrenaline, thyroxine, increased venous return etc. while it decreases with parasymp. stimulation. IV. TOTAL PERIPHERAL RESISTANCE:- Acts as Afterload against which heart has to pump blood. Increase in peripheral resistance(vasoconstriction)initially decreases cardiac output, but later comes to normal. Decrease in peripheral resistance (eg. anemia, beriberi, hyperthyroidism)results in increase in cardiac output by increasing venous return. Cardiac function curve: is plotted with cardiac output on vertical axis and right atrial pressure on horizontal axis. It shifts downwards and to the right in hypoeffective heart. *Q. DESCRIBE THE METHOD FOR MEASUREMENT OF CARDIAC OUTPUT IN MAN: Cardiac output is the quantity of blood pumped by each ventricle of heart in one minute. Normal value:5 to 5.6 lit/min. Suggestions: facebook.com/asifpatel.ggmc

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Methods for determination of cardiac output in man are: 1.Fick principle method (Adolph Fick, 1870): Fick principle states that "the volume of gas taken up by an organ is proportional to the blood flow through that organ times the arteriovenous difference of that gas in blood". Therefore if volume of gas consumed by an organ in one minute and the AV difference of that as in blood is known, then blood flow through that organ can be calculated. Fick principle method using Oxygen:-In this method blood flow through the lungs, which is same as cardiac output, is measured by a)determination of O2 consumption by lungs in 1 minute by using Douglas bag or metabolator(Say 250ml/min) b)O2 content of arterial blood is measured by taking a blood sample from femoral artery and using blood gas analyzer(Say 190 ml/min) C)O2 content of mixed venous blood is measured by taking a sample of blood from pulmonary artery by cardiac catheterization(Say 140 ml/min)Then Cardiac output in lit/min= (O2 consumption/min)/(AV O2 difference/litre) (or pulmonary blood flow)= (250 ml)/190-140 ml =5 lit/min This principle can also be used to measure cardiac output using CO2. 2.Hamiltons Dye dilution(Indicator dilution) Method Principle: In this method, the degree of dilution of a known quantity of dye injected into blood for one circulation is measured. The dye commonly used is cardiogreen or Evan's blue. It is non-toxic, is not lost from circulation, does not affect cardiac output and can be easily measured. A known quantity of dye(say 5 mg)is injected, rapidly into anticubetal vein or in the right atrium and arterial blood is continuously drawn through a densitometer to measure the concentration of dye. Then a time - concentration curve is plotted. The curve shows initial rise to peak(head),then fall in concentration(tail)and then another rise due to recirculation of the dye. The initial downslope of the curve is extrapolated to the baseline and the time for one circulation of dye is measured(say 24 sec).The area of the curve is uniformly distributed over this time interval to find out the average concentration of dye for this period(say 2.5 mg/lit). Then, Cardiac output = {O2 consumption/min}/(A-V O2 difference / litre) = 250 ml/(190-140)ml = 5 litres/min 3. Thermodilution Method:- Here, the degree of dilution of cold saline is measured. A cardiac catheter with thermister probe is inserted till the probe lies in pulmonary artery. Through the lumen of catheter, known quantity of cold saline is injected into right atrium and change in blood temp in pulm. artery is noted. Rise in temp will be proportionate to cardiac output. The advantage of this method is that there is no recirculation. 4.Other methods like Ballistocardiography, Pulse pressure method, Echocardiography can also be used to measure cardiac output in human beings.

*Q. DEFINE SHOCK, DESCRIBE VARIOUS CHANGES TAKING PLACE IN THE BODY DURING HYPOVOLEMIC SHOCK. Circulatory shock means generalized inadequate blood ﬂow throughout the body, to the extent that the body tissues are damaged because of too little ﬂow, especially because of too little oxygen and other nutrients delivered to the tissue cells. Even the cardiovascular system itself—the heart musculature, walls of the blood vessels, vasomotor system, and other circulatory parts—begins to deteriorate,

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46 so that the shock, once begun, is prone to become progressively worse. Definition- Circulatory shock is defined as a condition in which there is generalized decrease in blood flow to all tissues of the body leading to reduced supply of oxygen and other nutrients to the cell. Hypovolemic shock results from loss of blood(hemorrhagic shock) or from loss of fluids from body e.g. Dehydration, burns etc. Changes taking place in hypovolemic shock occur in 3 stages: A) Nonprogressive or Compensated stage In this stage following compensatory mechanisms are initiated to maintain blood pressure and cardiac output: 1.Baroreceptor reflexes : Fall in arterial pressure decreases Baroreceptor discharge leading to strong stimulation of the Vasomotor centre and increased sympathetic discharge throughout the body. Therefore, there is 1.Constriction of peripheral Arterioles, 2. Increase in heart rate and force of contraction, 3.Venoconstriction, 4. Cutaneous and splanchnic vasoconstriction, 5. Release of adrenaline, all of which increase blood pressure and cardiac output. 2.Chemoreceptor reflexes :- decreased blood flow to the Chemoreceptors in carotid and aortic bodies, stimulates them causing excitation of VMC and increased respiration 3. CNS Ischemic response :- is initiated by decreased flow to VMC causing its strong activation and mass sympathetic discharge. 4. Renin – Angiotensin mechanism :- fall in renal blood flow or renal arterial pressure bring about release of renin from JG cells which then forms Angiotensin II which is a very potent vasoconstrictor agent. 5. Vasopressin vasoconstrictor mechanism :- decreased blood volume in rt. Atrium brings about release of large amount of vasopressin which is also a potent vasoconstrictor. 6. Reabsorption of tissue fluid (capillary fluid shift) :- Fall in intracapillary pressure facilitates fluid reabsorption into the circulation to maintain effective circulating blood volume. 7. Reverse relaxation :- gradual contraction of smooth muscle in the veins decreases there capacitance and returns more blood to the heart. 8. Fluid retention occurs due to increase in renal blood flow And G.F.R. 9. Increased aldosterone secretion brought about by angiotensin II cause retention of Na+ and H2O leading to increase in ECF volume and blood volume. 10. Anti Diuretic action of vasopressin (ADH) increases reabsorption of water from kidneys and helps to restore E.C.F volume.

B) Progressive stage: It is associated with many positive feedback mechanisms which worsen the condition (Vicious cycle) unless promptly treated. 1. Cardiac depression : decreased

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coronary flow reduces myocardial contractility and cardiac output, further decreases coronary blood flow and the cycle continues. 2. Failure of vasomotor centre : Decreased blood flow initially stimulates, but after 10-15 min, depresses VMC leading to loss of vasomotor tone and peripheral vasodilation. 3. Acidosis: Hypoxic cells produce lactic acid, excretion of H+ ions is reduced. Resulting metabolic acidosis depresses the heart. 4. Formation of multiple thrombin due to sluggish blood flow and release of thromboxane A2 . 5. Transudation of fluid into the tissues: - Occurs from prolonged hypoxia of capillary cells. 6. Toxemia:- results from failure of antibacterial defense mechanism of R.E. cells.

7. Cellular changes:- a. Damage to Na pump and swelling of cells b. mitochondria degenerate c. rupture of lysosomes causes cell damages. III. Irreversible stage:

All the positive feedback reach stage of no return. Hence survival is not possible. Cellular energy compounds are extremely depleted.

*Q. Describe The Cardio Vascular Changes Taking Place During Muscular Exercise:-

Exercise is a condition of physiological stress associated with increased muscular activity. It is accompanied by extensive changes in cardiovascular and respiratory system to provide adequate oxygen and nutrients to exercising muscles and to drain their metabolites, of heat generated by contracting muscles.

1. Increases in cardiac output: - Cardiac output increases in proportion to severity of exercise rising to 25 to 30 lit/mi in sever exercise. It from increase in heart rate and stroke volume.

a) Increases in stroke volume results mainly from positive isotropic effect of sympathetic stimulation. Since the end diastolic volume does not show any change, frank starling’s mechanism does not contribute significantly to increases in stroke volume. b) Increases in heart rate:- Heart rate increases at the onset of exercise due to impulses coming to medullary centres from motor cortex. As exercise continues, heart rate increases upto 180-200/min. Factors increasing the heart rate are 1.decreased vagal tone 2. increased sympathetic discharge. 3. Release of adrenaline from adrenal medulla. 4. Reflexes arising from receptors in muscles and joints, 5. increased body temperature. 6. Bainbridge reflex. Increases in heart rate contributes more to increases in cardiac output to severe exercise because rise in stroke volume reaches maximum in moderate exercise. 2. Increases in Venous Return:- Results from 1. Vasodilation in exercising muscles. 2.Skeletal muscle pump. 3. Respiratory pump. 4. sympathetic vasoconstriction 5. Blood mobilization from splanchnic circulation. Increased venous return ensures adequate filing of ventricles despite shorter duration of diastole. Suggestions: facebook.com/asifpatel.ggmc

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48 3. Changes in arterial pressure:- systolic pressure increases because of increased force of myocardial contraction. In mild exercise or isometric exercise, diastolic pressure increases because generalized sympathetic vasoconstriction is stronger than muscle vasodilatation, but in severe, whole body exercise, reverse occurs and diastolic pressure falls. Thus in exercise, there is mild to moderate increases in mean arterial pressure. 4. Total Peripheral Resistance:- Show a mild to moderate decrease denuding upon the number of dilated vessels. 5.Mean systemic filing pressure:- Increases due to sympathetic vasoconstriction. 6. Work done by heart and myocardial oxygen consumption increased. Change in regional circulations:

7. Vessels of Skeletal muscles:- There is dilation of arterioles initially due to action of adrenaline on vascular beta two receptors and increased discharge through sympathetic cholinergic vasodilator fibers. Later, cellular metabolites like K ions H ions, adenosine etc. act on vascular smooth muscles and dilate them. There is also transudation of fluid into the muscles and more lymph flow. In severe exercise, muscle blood flow increases 2025 times, increased flow occurring during relaxation. Oxygen extraction is increased. 8. Coronary blood flow increases in proportion to work done by heart (metabolic regulation).

9 Splanchnic vasoconstriction results from increased symp. discharge and helps to redistribute blood. 10. Pulmonary blood flow increases with right ventricular output. 11. Cerebral blood flow remains constant.

12. Cutaneous blood vessels initially constrict (symp. effect) but later dilate to promote heart loss. 13. Circulation becomes hyperdynamic.

*Q. Describe The Salient Features of Coronary Circulation.

Functional anatomy:- 1. Heart is supplied by right and left coronary arteries. In 50% humans, right coronary artery has greater blood flow (dominant) and supplies rt. Side of heart and also some part of left ventricles. In 20% left coronary is dominant and in 30%, flow is equal in both.

2. Coronary arteries arise from sinuses behind the cusps of aortic valve and eddy currents keep the valve leaflets away from coronary ostia. 3. Venous blood from heart is drained through coronary sinus (from left side), ant. Cardiac veins (right side) and directly into cavities by art rosin zooidal, and the basin vessels.

4. Coronary arteries are and arteries but new collateral vessels develop gradually after occlusion of coronaries. 5. Capillary density of myocardium, especially on endocardial side, is very high (400/sq.mm). Normal Value:- Average human resting coronary flow is 225 to 250 ml/mi for whole heart fo 70-80 ml/min/100 gm or 4 to 5 % of cardiac output. Oxygen consumption by heart in resting state is 28 to 30 ml/min. Oxygen extraction rate is high (70%). Phasic variations in Coronary flow:Results from 2 factors:

1. Changes in aortic pressure which is the driving when the ventricles contract. (Systolic compression or extra coronary resistance). Suggestions: facebook.com/asifpatel.ggmc

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2. Pressure on subendocardial vessels is maximum during systole. Because of the above two factors, coronary flow falls in isometric constriction phase, rises in rapid ejection phase, falls in reduced ejection phase.

Rises maximally in isometric relaxation and slowly in first rapid filling phase and then falls slowly in diastasis and last rapid filling phase. Regulation of Coronary Flow:-

A) Metabolic regulation:- Coronary flow is regulated exactly in proportion to myocardial oxygen consumption, which depends on work done by heart. A decreases in oxygen availability to myocardium results in production of vasodilator metabolites like adenosine, K ions, H ions bradykinins etc. Adenosine is formed by breakdown of ATP, diffuses out of myocardial cell and is a potent vasodilator (Berne’s theory). Direct action of hypoxia on coronary smooth muscles is also one of the factors producing vasodilatation. Coronary vasodilatation is the only available mechanism to increases O2 supply to myocardium because oxygen extraction is already high. Auto regulation:-Maintains coronary flow constant in spite of wide variation in arterial pressure from 60-150 mm of Hg.

B) Neural regulation:- Stimulation of sympathetic fibers that supply coronaries results in vasoconstriction due to action of nor adrenaline on alpha receptors. But this effect is overridden by sympathetic stimulation of myocardium leading to coronary dilatation. Parasympathetic stimulation produces coronary dilatation. Other factors affecting coronary flow:-

1. Heart rate:- Increases in heart rate decreases duration of diastole and hence coronary flow.

2. Hormones like thyroxine, adrenaline increases while angiotensin II, vasopressin decrease coronary flow. 3. Exercise increases coronary flow. 4. Amyl nitrite dilates coronaries. Applied Physiology:- Development of athermanous plague can cause narrowing of vessels leading to coronary heart disease. Formation of thrombus may totally block the vessels leading to ischemia and myocardial infarction. Q. Describe The Physiology Of Cerebral Circulation.

Functional Anatomy:- Blood supply to the brain is derived from: two Internal carotid and two Vertebral arteries. They divide and join to form circle of Willis at the base of brain from which anterior, middle and posterior cerebral arteries arise. Venous blood is drained through dural sinuses ultimately into the internal jugular veins.

Normal Values :- Normal total cerebral flow is 750-800 ml/min or 15% of cardiac output or 50-55 ml/min/100 gm. Normal O2 consumption by brain is 45 ml/min most of which is consumed by grey mater, normal AV Oxygen difference- 6.2 ml/100 l blood. Regulation of cerebral flow:- The cerebral circulation is regulated precisely so that the total quantity of blood flowing into the brain remains constant in a variety of conditions.

1. Regional Variation:- Cerebral flow shows marked regional fluctuations. For example occipital blood flow increases when light is flashed into the eye or blood flow in hand area of left motor cortex increases when right hand is clenched and so on. This increases is compensated elsewhere so that total flow remains constant. 2. Metabolic regulation:- Cerebral blood flow is closely related to metabolism of brain tissue. The metabolic factors that are involved are: 1. PCO2: Increases in CO2 conc. of brain tissue or arterial blood causes cerebral vasodilatation and increases blood arterial flow. This action of CO2 is due to formation of H ions which dilate fluid from any source (lactic acid, pyruvic acid etc.) dilate cerebral vessels. 3. Oxygen lack: Causes production of Suggestions: facebook.com/asifpatel.ggmc

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50 vasodilator metabolites like adenosine and K ions which increases cerebral flow. 4. Direct action of hypoxia on cerabrovascular smooth muscle also causes their dilatation.

3.Autoregulation :- Cerebral flow remains constant despite changes in arterial pressure from 60 mmHg to 140 mm Hg. This is called auto regulation and is attributed to 1) Metabolic factors (above) and 2) Myogenic response is initiated.

4. Neural regulation:- Stimulation of sympathetic fibers supplying cerebral vessels causes mild vasoconstriction which is a weak effect and is overcome by metabolic regulation. However, symp, Stimulation prevents rupture of capillaries and cerebral edema during extreme rise of blood pressure by causing vasoconstriction. Factors affecting cerebral blood flow:-

1. Intracranial pressure:- Rise in intracranial pressure decreases cerebral flow by compressing cerebral vessels because the brain, the CSF and the blood vessels are enclosed in rigid cranium. CNS ischemic response initiated by rise in intracranial pressure is called Cushing's reflex. 2. Effective perfusion Pressure is the difference between man arterial pressure and internal jugular pressure 3. Cerebrovascular resistance: - cerebral flow is inversely related to resistance. 4. Viscosity of Blood :- Increase in viscosity (polycythemia) increases resistance and decreased cerebral flow. 5. Anesthetics :- Decrease cerebral flow.

6. Angiotensin II: - Constricts cerebral vessels. Another special feature of cerebral circulation of decreased permeability of cerebral capillaries called Blood Brain Barrier which regulations composition of brain tissue fluid Measurement of cerebral flow is done by using N2O and applying Fick principle (Katy method.) Applied physiology: - In old age, cerebral blood flow decreases due to arteriosclerosis. In hypertension, auto regulation is set at higher level. *Q. Describe the Regulation of Heart Rate:

Normal heart rate in resting conditions is between 70-80 beats/ min. (Range 60 to 90). It is regulated in accordance with the needs of the body to 1. Maintain optimum blood pressure and. 2. To provide adequate blood flow to the tissues. Under physiological conditions, regulation of heart rate is mainly brought about by changes in vagal tone. A) Local Mechanisms regulating heart rate:- Include the factors which have direct action on pacemaker S.A. node. For example. 1. Hormones like thyroxine, and adrenaline increase heart rate.

2. Increased temp. of blood bathing S.A. node increases heart rate. 3. Local stretching of S.A. node by increased venous return rate.

B) Sino-aortic (Marey’s reflex) :- Rise in blood pressure stimulates baroreceptors leading to stimulation of Cardio inhibitory centre (Nucleus ambiguus)in medulla and increase in vagal tone. Sympathetic discharge to the heart is reduced. Thus heart rate decreases. Opposite changes occur when blood pressure falls.

C) Reflex arising from stretch receptors in left ventricle and pulmonary artery:- Increases in vagal tone and decreases in heart rate.

D) Coronary Chemo reflex :- Arises from stimulation of coronary chemoreceptor’s and leads to reflex bradycardia and hypotension. Suggestions: facebook.com/asifpatel.ggmc

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E) Cardioaccelerator reflexes:- 1. Bainbridge Reflex: Initiated by damming of blood in right atrium and base of great veins which stimulates type B receptors producing reflex decrease in vagal tone and tachycardia.

F) Reflexes arising from peripheral chemoreceptor’s :- Decrease in pO2 stimulates carotid chemoreceptor’s leading to stimulation of respiratory centre and inhibition of vagal centre, thus increasing heart rate.

G) Reflexes arising from other parts of body can also change heart rate e.g. painful stimulus arising from any part of body increases heart rate while a sudden blow on abdomen or pressure on outer angle of eye decreases heart rate. Other factors affecting heart rate:-

1. Role of higher centers :- Emotions like anxiety, fear, anger, etc. Increases heart rate by stimulating medullary cardioacelerator centre’s and by releases of adrenaline. Stimulation of orbit frontal cortex and post. Hypothalamus also increases heart rate. 2. Effect of Respiration: - Heart rate increases during inspiration and decreases during expiration. This is called Respiration sings Arrhythmia and is due to inhibition of vagal center’s during inspiration by a) Stretch receptors in lungs b) Bainbridge reflex c) respiratory centre. 3. Exercise: - Heart rate increases during exercise due to

a. Decreased vagal tone. b. increased symp. discharge to heart

c. Release of adrenaline. d. Reflexes arising from proprioceptors

e. Bainbridge reflex and f. Increase in body temp. In severe exercise, increase in heart rate contributes more to increases in cardiac output than stroke volume.

4. Increase in intracranial Pressure:- Decreases heart rate by stimulating vagus.

5. Temperature:- From lying to standing increases heart rate through baroreceptors reflex.

7. Digestion and sleep:- Heart rate increases during digestion and decreases in deep sleep. 8. Athletes:- Have less heart rate due to increased vagal tone. 9. Size :- Heart rate is inversely related to size of animal.

*Q. Describe the Peculiarities of Pulmonary Circulation:-

1. Functional anatomy:- a) Deoxygenated blood pumped by right ventricle enters lungs through pulmonary artery, gets oxygenated and returns to left arteries, supplies bronchi and bronchioles and deoxygenated blood returns to left atrium through bronchial veins (Physiologic shunt). 2. Normal value :- 5 to 5.5 L/min (same as cardiac output).

3. It is a low pressure circulation. In pulmonary artery, systolic pressure is 25 mm Hg and diastolic pressure 8-10 mm Hg. Pulmonary capillaries 8 mm Hg, Pulmonary vein 5 mm Hg.

4. It is a low resistance circulation. Pulmonary vascular resistance is very less (0.14 PRU) as compared to systemic circulation because of large diameter, than will and less number of smooth muscle fibers in pulmonary arterioles. Low resistance decrease work load of right ventricle.

5. Sheet Flow:- Volume of blood in lungs at any instance is about 450 ml of which 70 ml is present in capillaries spread over an area of 70-80 m (respiratory membrane). Thus blood flows in the form of thin sheet surrounding the alveoli. 6. Reservoir function:- Lungs can hold large volume of blood because of high compliance of pulmonary vessels especially in left heart failure. Suggestions: facebook.com/asifpatel.ggmc

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52 7. Increase in pulmonary blood flow, as occurs during exercise, results from 1. Distension of already open capillaries. 2. Opening up of dormant capillaries:-

8. Regulation of Pulmonary blood flow:-

a) Local or active regulation :- Po2 of alveolar air is the most important factor. Decrease in PO2 (or rise in PCO2) in alveolar air causes constriction of smooth muscle of adjacent pulmonary arterioles and diverts blood to well ventilated alveoli. Thus this mechanism controls local blood flow:- In different parts of lungs in proportion to their degree of ventilation and maintains V.P. ratio. b) Neural regulation:- simulation of Sino-aortic baroreceptors produces dilation while stimulation of receptors by emboli produces constriction of pulmonary vessels. c) Chemicals like adrenaline, serotonin, thromboxane A2 cause constriction where as acetyl choline, prostacycoin cause dilatation of pulmonary vessels. 9. Effect of hydrostatic pressure:- In erect posture, apical parts of lungs are at a higher level than heart. Hence blood flow to these parts is less and occurs only in systole.

10. Effect of Alveolar pressure:- Alveolar pressure has a compressing effect on alveolar capillaries. As a result of hydostatic and alveolar pressure, there are 3 zones in lungs depending upon flow- zone 1- no flow because alveolar pressure exceeds capillary pressure, zone 2- blood flow only during systole and zone 3- flow in systole and diastole. 11. Effect of Respiration:- During inspiration, intrathoracic pressure becomes more negative pulmonary vessels distend and hold more blood.

12. No tissue fluid formation :- Because of low pulmonary capillary hydrostatic pressure, the inward and outward forces acting on pulmonary capillaries are almost balanced and there is very little tissue fluid formation. Moreover, the negative interstitial pressure has sucking effect on alveolar fluid and keeps the alveoli dry. 13. Functional importance of Pulmonary circulation:-

a) Oxygenation of blood b) filtration of emboli c) conversion of Angiotensin I to Ang. II.

Applied aspects:- a. At high altitudes, chronic hypoxia leads to pulmonary hypertension. b) Positive pressure breathing decrease pulmonary blood flow. *Q. Describe The Process of Tissue Fluid Formation. What are the Functions of lymph?

Tissue fluid formation occurs in tissue capillaries and is due to filtration of fluid. The process is essentially a physical one and depends upon balance of forces acting on capillary walls.

1. Principal Hydrostatic Pressure :- Favors filtration of fluid into the tissue spaces. Normally it is 30 mm of Hg. at arterial end of capillary, 10 mm Hg. at venous end and 17 mm Hg. average. It can increase by arteriolar dilatation or venous obstruction. 2. Interstitial fluid pressure:- Normally it is about- 3 mm Hg. as measured by implanted perforated capsule and since it is negative, it pulls the fluid into the tissues and favours filtration.

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3. Colloid Osmotic Pressure of Plasma:- It is normally 28 mm of Hg. and tries to draw the fluid into the capillaries, that is it oppose filtration. It is mainly due to osmotic activity of albumin (and other plasma proteins) and also due to electrolytes held by negatively charged proteins (Donnan effect). 4. Tissue fluid colloid osmotic pressure:- It is normally about 8 mm Hg. and drag fluid from capillaries, i.e. It favours filtration. It is due to small quantity of albumin present in tissue fluid. Filtration at arterial end of capillaries:A) Total forces favoring filtration are : 30+3+8= 41 mm Hg.

B) Total force opposing filtration are : 28 mm Hg.

Therefore, there is a net filtration pressure of 13 mm of Hg. which cause filtration of about 0.5 % plasma into the tissue spaces. Reabsorption at Venous end of capillaries.

A) Force favoring filtration = 10+3+8= 21 mmHg. B) Force favouring reabsorption = 28 mmHg.

Hence there is a net reabsorption pressure of 7 mm Hg which reabsorbs 90% of filtration plasma back into the venous end of capillaries. The remaining unabsorbed tissue fluid forms the lymph. On an average, about 2 ml of tissue fluid is formed in the entire body per minute for a pressure gradient of 0.3 mm Hg, thus giving a filtration co-efficient of 6.67 ml/min/mm Hg.

The lymph is returned to the heart via the thoracic duct and right lymphatic duct. The draining of lymph is facilitated by rise in tissue pressure, skeletal muscle activity, contraction of lymphatic vessels (pump) and one way valves. Total lymph flow in 24 hours in about 2.8 liters. Functions of Lymph:

1. Return of fluid:- Lymph return the fluid has been filtered but not absorbed by capillaries. Volume is 2.8 L/day.

2. Return of proteins:- Proteins that have leaked through the capillaries into the tissue spaces returned to circulation, in the absence of which plasma proteins would fall.

3. Controls interstitial fluid proteins:- By returning proteins, it prevents rise in tissue fluid colloid osmotic pressure. 4. Controls interstitial fluid Volume and prevents edema by draining the proteins.

5. Controls interstitial fluid pressure:- By preventing accumulation of proteins and fluid in tissue spaces. Rise in interstitial fluid pressure causes increase in lymph flow so that pressure falls back to normal. 6. Antibacterial function :- The bacteria, parasites and other particulate matter are drained to the lymph nodes where appropriate action take place. Short Notes :

Q. Phlebogram (Jugular venous pulse) :-

It is a record of pulsations of jugular veins obtained by placing a cup or tambour over the jugular veins consented to a recording device or by using a polygraph. These pulsations are produced due to pressure Suggestions: facebook.com/asifpatel.ggmc

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54 changes taking place in right atrium and transmitted to jugular because there are no valves between right atrium and jugular vein.

A Phlebogram shows 3 positive deflections are a, c and v; negative waves are X, X1 and Y. A wave: is due to a trial systole. In times phase, right atrial pressure increase. Hence jugular veins cannot empty their blood leading to rise in jugular pressure. X wave : Is due to atrial diastole producing fall in atrial pressure.

C wave:- Sharp wave due to sudden bulging of tricuspid value into right atrium during is volumetric contraction phase. Producing a rise in pressure in right atrium and therefore in jugular veins.

X wave:- It duet to 1) Fall in right atrial pressure because Av ring is pulled downward during repaid ejection phase 2) atrial diastole 3) ventricular contraction decreases pressure around heart and passively dilates atria.

V wave: - Due to gradual filling of right atrium with AV valves closed. Therefore, pressure rises in atria and jugular veins.

Y wave:- As ventricular diastole begins, AV valves open and blood gushes from atria to ventricles producing fall in atrial and jugular pressure.

Clinical significance:- 1) ac interval of phlebogram corresponds to PR interval of ECG. 2) a wave is absent in atrial fibrillation, giant a waves in tricuspid stenos is. Radial Pulse Tracing (Sphygmogram) :

It is a record of radial pulse obtained by using instruments like polygraph or Dudgeon’s sphygmograph.

Pulse is defined as the pressure change created by ejection of blood from left ventricle into already full aorta and transmitted as wave of expansion to the periphery. Pulse wave travels faster (5-7m/sec) than

blood flow.

The record shows an ascending limb called anecdotic limb and a descending limb called catachrestic notch. The wave following dichotic notch is called diacritic wave. In addition, there are multiple, small per and post dichotic waves.

The anecdotic limb is due to rapid ejection of blood into aorta. Catachrestic limb up to dichotic notch corresponds to reduced ejection phase. Dichotic notch indicates beginning of ventricular diastole. As ventricular pressure fall blood tries to roll back from aorta into left ventricle. This causes sharp fall in pressure and dichotic notch. Dichotic wave is due to closure of aortic valve and blood column is reflected back producing a positive wave. Pre and post dichotic wave as due to vibration of aortic walls. Applied physiology :- 1) Anacrotic pulse with prominent waves on upstroke seen in arctic stenosis. 2) Water hammer pulse (aortic incompetence) has vertical catachrestic limb. Q. Effect of Vagal Stimulation on Heart:-

Vagus carries preganglionic parasympathetic fibers to the heart. It arises from nucleus ambiguus (cardiac fibers) in medulla and ends on intraganglionic cells situated in myocardium near S.A. node and A.V. node. Intraganglionic cells are postganglionic parasympathetic cells which ultimately supply the myocardium. However, tip of the ventricle does not receive any parasympathetic supply. When vagus is stimulated, there is:-

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1) Decrease in heart rate (negative chronoscopic).

2) Decrease in excitability (negative bathmotropic).

3) Decrease in force of contraction (negative isotropic). 4) Decrease in conductivity (negative dromotropic).

All these inhibitory effects are due to release of acetyl choline from parasympathetic endings on myocardial cells. Ach increases membrane permeability to K ions which diffuse out of the cells causing their hyper polarization. Therefore the negative effects are seen.

With prolonged stimulation, initially there is complete stoppage of heart, but after some time, heart starts beating again. This is called vagal escape which is attributed to

1) idioventricular rhythm 2) exhaustion of Ach 3) tachyphylaxis 4) inactivation of Ach by cholinesterase 5) Sinoaortic reflex 6) Bainbridge reflex. Even in resting state, there is continuous discharge of impulses through vagus called vagal tone and in physiological conditions, regulation of heart rate is brought about mainly by alteration in vagal tone. Q. Cardiac Reserve :-

It is the maximum increase in cardiac output that can be achieved over and above resting cardiac output. It is expressed as percentage of resting cardiac output. Normally, in healthy adults, the cardiac output in resting state is 5 to 6 lit/min. During exercise it can rise to 25 lit/min in athlete. Thus cardiac reserve in common man is 300 to 400% and in athletes about 500%.

The reserve in cardiac output includes reserve in heart rate and reserve in stroke volume. Heart rate can increases from resting value of 70-80/ min, to as high as 200/min, thus reserve in heart rate is 120 to 130 beats /min. Similarly stroke volume can increases from resting volume of 70 ml to about 120- 130 ml, therefore reserve in stroke volume is 50 to 60 ml. Reserve work of the heat:- In the resting state work done by heart is 5-6 kg-m/min. While in maximum exercise it can rise to 80 kg-m/min, thus indicating a work resave of 75 kg-m/min. Applied Physiology:- Any factor that decreases as pumping ability disease, valvular heart diseases etc. There is no cardiac reserve in patients who are in cardiac failure.

Diagnosis of low cardiac reserve can be confirmed by exercise test on treadmill. As soon as the person with low reserve starts performing exercise, the small reserve is immediately utilized, the patient develops signs of cardiac insufficiency like extreme fatigue, dyspnoea and cyanosis. *Q. First Heart Sound:

Normally four heart sounds are produced during a cardiac cycle out of which first and second heart sounds are audible and the third and fourth can be detected only by phonocardiography. (Refer Wiggers diagram at the beginning of the chapter) First heart sound is the first sound produced in cardiac cycle.

Characteristic features:- 1) Occurs at the beginning of ventricular systole (of is volumetric constriction phase) 2) Nature: Loud, dull, prolonged and low pitched like the word LUBB. 3) Duration 0.14 sec. 4) Frequency: 20 to 45 CPS. 5) Coincides with apex beat and carotid pulsation 7) It comes after pause 8) Precedes the radial pulse 9) Coincide with peak of R wave of ECG 10) Precedes the C wave of Phlebogram. 11) During deep inspiration there is splitting of first heart sound because tricuspid valve closes little later then mitral valve. Suggestions: facebook.com/asifpatel.ggmc

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56 Causes :- 1) Vibrations of leaflets of AV valves immediately after their closure. 2) Vibrations of adjacent blood column and walls of the heart 3) Contraction of ventricular musculature 4) Turbulence created due to movement of blood. Applied aspects:- 1) Clinically, first heart sound indicates beginning of ventricular systole 2) It becomes under in left ventricular hypertrophy and feeble in prolonged PR interval.3) In bundle branch block, there is splitting of first heart sound. *Q. Second Heart Sound:-

Comes after the first heart sound and is produced by closing of semi lunar valves.

Characteristic features:- 1. Occurs at the beginning of ventricular diastole (actually at the end of protodiastolic period). 2) Nature:- less loud, short sharp and snapping like the word DUP. 3) Duration. 0.1 Sec. 4) Frequency: 45 to 55 ps 5) Clinically best heard over aortic (second right costosternal junction) and pulmonary (left second intercostals space 2 cm from sternal border) areas. 6) Comes after apex beat and carotid pulse 7) Comes before pause 8) Coincides with radial pulse 9) Concedes with ascending limb of T wave of XG 10) Coincides with Ascending limb of V wave of Phlebogram.

Causes :- It results from abrupt closure of semi lunar valves setting up 1) Vibrations of valve leaflets 2) Vibration of blood column and 3) Vibration of walls of great vessels and Ventricles. Greater tautness of valve leaflets explains shorter duration and higher frequency of second sound.

Applied Physiology: - 1. Clinically, it indicates beginning of Ventricular diastole and helps to differentiate systolic and diastolic murmurs. 2. It becomes louder in systemic and pulmonary hypertension and feeble in valvular incompetence. Q. T wave of E.C.G.:-

Electrocardiogram is a record of electrical changes taking place in heart during a cardiac cycle. It shows 5 waves, P.Q.R.S and T.

T wave is a broad rounded wave that comes after isoelectric ST segment. It has a voltage of 0.2 mv. Its duration is 0.27 Sec.

Cause:- T wave results from repolarization of ventricles. After the depolarization is complete, repolarization occurs due to efflux of K+ ions. The process of repolarization occurs earlier in epicardial fibres and processed from epicedial to endocardial side. Therefore, during repolarization also, the direction of current flow is from base to apex of the heart (same as that during depolarization). Thus T wave is recorded as positive wave even through it is a repolarization wave. Normally, it is negative in lead a VR, procurement in young adults and flattened in old age. Clinical Significance :- 1) Abnormalities of T wave in size, shape, direction and response to exercise indicate myocardial hypoxia. T wave is inverted (along with depression of ST segment) in myocardial ischemia and infarction because the duration of depolarization of damaged myocardium is increased. Hence current flow in opposite direction producing inverted T wave. 2) Changes in T wave after exercise indicated coronary insufficiency. 3) Digitalis toxicity causes biphasic T waves while hyperkalemia causes tall T wave. Q. Circulation Time

Definition:- It is the time taken by the blood to travel from one point in circulation to another. Different circulation times are measured using different substance. Suggestions: facebook.com/asifpatel.ggmc

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1) Arm to tongue circulation time:- Is the time required by the blood to flow from arm to tongue. It is measured by injecting like dacholine into the cubital vein and time is noted. When the substance arrives at the tongue, it produces a sensation of warmth (or bitterness) and again time is noted. The interval between the two is arm to tongue circulation time which is normally 12 to 14 Secs. 2) Arms to face time is measured by injecting histamine and observing flushing of faces (20 Sec). 3) Arm to heart circulation time:- Measured by radioactive isotopes (6 to 8 sec). 4) Total circulation time:- Measured by fluorescing day (20-25 Sec).

Clinical significance:- 1) It is gives an idea about dynamic state of circulation. It is increased in hyperkinetic states like of CCF, my edema, shock and polycythemia. It is decreased in hyperkinetic states like exercise, hyperthyroidism, anemia, fever, beriberi etc. 2) In left ventricular failures, prolongation of circulation time from lungs to brain is one of the factors responsible for Cheyenne stocks respiration. *Q. Reynolds’s Number (Turbulent Flow):-

Normally, blood flow in vessels is a streamline (laminar) flow. But when there is obstruction in blood vessel or when there is sharp turn, the flow becomes turbulent with formation of eddy currents. In this type of flow, fluid molecules move in different directions and collide with each other thereby increasing frictional resistance.

The tendency of the blood to develop turbulent flow is indicated by a number called Reynolds’s number, R. 1. tendency to turbulence is directly related to density of blood. 2. It is directly related to diameter of blood vessels, larger vessels or dilated vessels are more likely to develop turbulent flow. 3. It is directly related to velocity. When the velocity of blood flow exceeds a certain limit (critical velocity), flow becomes turbulent. 4. Tendency to turbulence is inversely related to viscosity, hence more likely in anemia (soft murmurs) and least likely in polycythemia. Clinical importance :- Turbulent flow produces sounds e.g. murmurs, kortkoff sounds etc. Q. Peripheral Resistance :Definition:- It is the resistance offered by the peripheral vessels to the flow of blood. The major seat of peripheral resistance in the body is arterioles (resistance vessels) because of their small diameter and smooth muscles in their walls. Resistance R = ∆P (Pressure gradient)/ Q (Blood flow) For systemic circulation, pressure gradient is 100 mmHg and blood flow is 100 ml/sc. (6l/min). Therefore peripheral resistance is 100 mmHg/100 ml= 1 Per. Resi. Unit. For pulmonary circulation it is 0.14 PRU. If Q is substituted by Poiseulle law in above equation, we get R= 8nl/πr4 where n (eta) is viscosity, l is length of blood vessel and r radius of blood vessel. Thus it can be seen that resistance is inversely proportional to fourth power of radius. That means a small decrease in arteriolar diameter. (Vasoconstriction in response to vasomotor impulses), will produce a large increase in peripheral resistance. Thus this is one of the important mechanisms to increase arterial pressure. When arterioles dilate, resistance as well as pressure falls. Peripheral resistance is directly proportional to viscosity of blood. Thus an increase in hematocrit value increase peripheral resistance. In addition, PR is directly proportional to velocity of blood flow and inversely to the elasticity of blood vessels. Clinical Importance: - PR is increased in conditions like essential hypertension, pheochromocytoma, polycythemia end decreased in anemia, beriberi, hypothyroidism etc. Hagen – Poiseulle’s Law :Suggestions: facebook.com/asifpatel.ggmc GGMC MUMBAI

58 Was put forward by Jean Poiseulle a French physicist. It is a mathematical expression that co-relates blood flow (Q) with other factors, According to this law. Q=∆Pπr4 /8 nl Where, P is pressure gradient along blood vessel, 'r' is radius of blood vessel, n (eta) is viscosity of blood and l is length of blood vessel. Therefore, it can seen that, 1. Blood flow is directly proportional to the pressure gradient along the vessel; greater the pressure gradient, more will be blood flow. 2. Blood flow is directly proportional to fourth power of radius of blood vessel. This is because of the fact that in a multilaminar flow, layer in contact with vessel wall flows very slowly, while central layers flow faster. When vessel diameter increase, central layers increases hence flow increases tremendously. Therefore a small increase in radius of blood vessel (vasodilatation) will bring about a large increases in blood flow. This is very important mechanism underlying regulation of blood flow in the body, neural regulation as well as metabolic regulation. 3. Blood flow is inversely related to viscosity, greater the viscosity (polycythemia), lesser the blood flow; lesser the viscosity (anemia), greater the blood flow. 4. Blood flow is inversely related to length of blood vessel however this factor doses not change in the body. Hagen Poiseulle's law is only applicable to Newtonian fluid (laminar flow) passing through rigid tube. *Q. CNS Ischemic Response :It is one of the rapidly acting neural mechanisms for regulation of arterial pressure intimated by ischemia of brain when the blood flow to the vasomotor centre decreases either due to fall in arterial pressure or any other factor, there is accumulation of carbon dioxide and hydrogen ions in the neurons of VMC: This leads to strong stimulation of VMC and massive sympathetic discharge through the body, leading to intense peripheral vasoconstriction, increases in heart rate and force of contraction, vasoconstriction, release of adrenaline etc. All these effects increase the arterial pressure and restore normal blood flow to vasomotor centre. This response is intimated only when arterial pressure falls very low (15 to 20 mmHg) and thus acts as last ditch stand to maintain blood pressure. CNS ischemic response is also initiated by increase in intracranial pressure which compresses cerebral vessels and decreases blood flow to VMC. This is called Cushing's reaction. If this response fails to relive ischemia in 10-15 min, (as happens in progressive stage of shock ) there is depression of VMC neurons and loss of vasomotor tone. *Q. Plateau Potential :-

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It is the type of action potential seen in atrial, and ventricular muscle and also in parking fibers. It is characterized by a flattened top or plateau. Such a plateau potential exhibits 5 phases :Phase O :- In which the membrane potential shoots rapidly from its resting value of 85 to 90 mv. It is due to rapid entry of Na ions through fast Na channels along electrochemical gradient. Phase 1 :- Is an early partial depolarization between the end of upstroke and beginning of plateau. It is due to transient outward current resulting from K efflux. Phase 2 :- Is the phase of plateau or sustained GGMC MUMBAI

depolarization lasting for 200 to 300 m sec. In this phase there is influx of Ca and Na ions through slow calcium sodium channels which is balanced by efflux of K ions. Phase 3 :- Is the phase of rapid depolarization following the plateau. It is due to efflux of K ions along conc. gradient. Phase 4 :- Is the resting phase, the membrane potential remaining at 85 to 90 mc. Significance of plateau potential- 1) During plateau phase, calcium ions continue to enter myocardial cells continuing process of contraction. Therefore contraction period lasts for the same duration as plateau. 2) During plateau phase, fast Na channels remain inactivated therefore muscle fiber does not respond to a second stimulus. Thus cardiac muscle has along refractory period. *Q. Frank Starling’s Law of Heart :Put forward by Frank of Germany and Emits Starling of Britain. It states that “Within physiological limits, greater the end diastolic length, stronger is the force of contraction”. The end diastolic fiber length (initial Length) depends upon end diastolic volume (venous return). Hence more the end diastolic volume, stronger is the force of ventricular contraction. Thus this is an intrinsic mechanism that regulates contractility in accordance with venous return (heterometric regulation) and enables the heart to pump all the blood it receives, back into circulation. The end diastolic volume acts as preload. Basis of starling’s law: If a length-tension curve of cardiac muscle is plotted, it will be seen that force generated is maximum at sarcomere length of 2 to 2.4 microns because at this length there is maximum cycling activity of cross bridges between actin and myosin filaments. Sarcomere lengths greater or lesser than this decrease force of contraction. There is also increased sensitivity of myofilaments to calcium when muscle fiber is stretched. Importance of Frank Staring Mechanism:1) It changes stroke volume in response to changes in venous return. 2) It maintains a balance between the output of left and right ventricle. 3) It is a life saving mechanism in Cardiac failure.

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RESPIRATORY SYSTEM

Chapter 5

*Q. Discuss the Mechanical Factors Affecting Expansion of Lungs. In human beings, there is negative pressure breathing. During inspiration, alveolar pressure falls, therefore atmospheric air moves into lungs, During expiration opposite changes take place.

A) Factors promoting expansion of lungs:1) Action of Inspiratory muscles:- a) Contraction of diaphragm causes its descent into the abdomen and increases vertical diameter of chest cavity b) Contraction of external intercostals muscles results in 2 effects: i) upper ribs swing upwards and forwards increasing the AP diameter of chest (pump handle movement) ii) Lower ribs swing upwards and outwards leading to increase in transverse diameter of chest (Bucket handle movement). Thus the expansion of chest leads to expansion of lungs. 2) Intrapleural pressure:- Normally intrapleural pressure is negative (-5 cm of H2O) in end expiratory state. During inspiration, as the chest expands, the parietal pleura is pulled outwards by expanding chest cage. As a result, intrapleural pressure becomes more negative and pulls visceral pleura outwards, thus bringing about expansion of lungs. 3) Surfactant: It is a mixture of phospholipids(dipalmitoyl lecithin, apoproteins and calcium ions) secreted by type II alveolar cells. These phospholipid molecules align themselves at the air-liquid interface in alveoli and decrease intermolecular attraction forces. Therefore, surface tension and the resulting collapsing tendency of alveoli is reduced. It also stabilizes the alveoli and ensures uniform expansion of lungs. 4. Outward recoil of chest wall: In the end expiratory state(FRC), the chest wall has a tendency to recoil outwards which also facilitates expansion of lungs. B) Factors opposing expansion of lungs: 1. Surface tension of fluid lining the alveoli: The force of intermolecular attraction at the air-liquid interface tries to contract the alveoli and increase their tendency to collapse. It thus opposes expansion. Surface tension accounts for two thirds of recoil tendency of lungs. 2. Elastic recoil of lungs: Lung parenchyma contains large no. of elastic fibers which resist expansion and which have a tendency to shorten when stretched. This is known as elastic recoil of lungs which increases collapsing tendency. Lungs also contain collagen fibers which oppose expansion. 3) Viscous properties of lung tissue, frictional resistance and inertia of lungs, all these factors oppose the expansion of lungs, especially in the initial phase of inspiration. 4) Airway resistance :- Is the reference offered by airways to the flow of air. Airway resistance during inspiration opposes lung expansion. It depends upon a) diameter of bronchi and bronchioles (bronchoSuggestions: facebook.com/asifpatel.ggmc

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constriction oppose expansion. b) Nature of air flow- turbulent (more resistance) or streamline c) Velocity of air flow. Expansibility of lungs is expressed by the term lung compliance which is defined as change in lung volume per unit change in Transpulmonary pressure. Its normal value is 0.2 L/cm of H2O. Applied physiology :- Expansion of lungs is affected in variety of disease conditions like paralysis of respiratory muscles(polio, myasthenia gravis), loss of interapleural negativity (pneumothorax, pl. effusion), reduced surfactant secretion(respiratory distress syndrome), Increased stiffness of lungs (fibrosis, congestion) or deformities of chest cage (kyphosis, scoliosis). *Q. Describe The Neural Regulation of Respiration :Normally the rate and depth of respiration (pulmonary ventilation) are regulated in accordance with the needs of the body and to maintain arterial pO2, pCO2 and pH constant. Neural regulation consists of parts and functions of respiratory centre and various reflexes which modify respiration. Respiratory centre :- Is a group of neurons situated bilaterally in reticular formation of brain stem which control respiration. These neurons are arranged in 4 groups:

1) Dorsal Respiratory Group (DRG) Situation :- Situated dorsomedially in the medulla extending vertically in and around nucleus of Tractus solitarius. Afferents:- Receives afferents through vagus and glossopharyngeal nerves (baro and chemoreceptor’s) and also from ascending and descending tracts. Efferents :- Pass through reticulospinal tract and end on contralateral spinal motor neurons from which phrenic nerve arises to supply diaphragm (C5, 6). Actions :- 1. DRG neurons are responsible for normal inspiration and rhythm of respiration, since they supply diaphragm which is the muscle of inspirations in quiet breathing. 2. The DRG neurons exhibit spontaneous discharge of action potentials at the rate of 12-15/- min, which is also the normal respiratory rate. 3. Discharge from DRG neurons to in inspiratory muscles is called Ramp signal. It is weak in the beginning, become stronger as inspiration process and stops after 2 seconds. It ensures smooth progressive expansion of lungs and also permits. 2) Ventral Respiratory Group (VRG):Situation :- Situated 5 mm ventral and lateral to DRG neurons in medulla in nucleus ambiguus and retroambiguus. Afferent: - From DRG neurons. Efferent :- Supply muscles of inspiration as well as expiration, especially the latter. Actions: - when DRG neurons are strongly stimulated, they activate VRG neurons leading to increased pulmonary ventilation. They remain inactive in normal quiet breathing. 3) Pneumotoxic :Suggestions: facebook.com/asifpatel.ggmc

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Situation :- In upper pons dorsally in nucleus parabrachialis. Afferents :- from DRG neurons and apneustic centre. Actions: - a) Sends afferent impulses to DRG neurons and cause early switch off of inspiratory ramp signal. It therefore limits the phase of inspiration and secondarily increases the rate of respiration. b) It keeps apneustic centre inhabited. 4) Apneustic centre: - Situated in lower pons. Action :- Prevents switch off of ramp signal and prolongs inspiration (apneusis). Normally it is kept inhibited by DRG and vagal afferents. Overall Regulation :- Normally quiet respiration (rate, depth and rhythm) results from action of DRG neurons, while VRG neurons are responsible for increasing pulmonary ventilation when respiratory drive increases. Pneumotaxic and Apneusitc centers can modify respiration signals under certain conditions. Reflexes Modifying respiration are :1) Herring- Breuer reflex- initiated by lung inflation above. 2) To 1.5 lit. It limits inspiration and prevents over distension. 3) Reflexes from higher centers e.g. emotional modification of respiration like fear, anger increases respiration. 4) Reflexes from baroreceptors stimulate respiration. 5) Reflexes from chemoreceptor’s stimulate respiration. 6) Reflexes from proprioceptors stimulate respiration. 7) Reflexes from J receptors produce shallow respiration. 8) Reflexes from skin receptors, pain receptors, cough reflex, sneeze reflex, Regulation can all modify respiration.

ONDINE'S CURSE

Ondine's curse is a very rare and serious form of central nervous system failure, involving a failure of autonomic control of breathing. It is also called as congenital central hypoventilation syndrome (CCHS) or primary alveolar hypoventilation. CCHS is a respiratory disorder that is fatal if untreated. Signs and symptoms: Ondine's curse is associated with 1. Respiratory arrests during sleep. 2. Neuroblastoma (tumors of the sympathetic ganglia), Hirschsprung disease (partial agenesis of the enteric nervous system). 3. Dysphagia (difficulty swallowing) and anomalies of the pupilla. 4. Increased sensitivity to sedatives and narcotics, which makes respiration even more difficult. 5. Other symptoms: Darkening of skin color from inadequate amounts of oxygen, drowsiness, fatigue, headaches, and inability to sleep at night. Complications: A low concentration of oxygen in the red blood cells may cause hypoxia-induced pulmonary vasoconstriction and pulmonary hypertension, resulting in cor pulmonale or failure of the right side of the heart. Other complications: Gastro-esophageal reflux, ophthalmologic issues, seizures, recurrent pneumonia, developmental delays, learning disabilities and episodes of fainting and temperature dysregulation. Causes: Ondine's curse is exhibited typically as a congenital disorder, but in rare circumstances, can also result from severe brain or spinal injury. Treatment and prognosis: Patients generally require tracheostomy and lifetime mechanical ventilation. However, Biphasic Cuirass Ventilation can effectively be used without the need for a tracheotomy. Other treatments: Oxygen therapy and medicine for stimulating the respiratory system.(Currently problems arise with the extended use of ventilators, including fatal infections and pneumonia). Suggestions: facebook.com/asifpatel.ggmc

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Most people with Ondine's curse (unless they have the Late Onset form) do not survive infancy, unless they receive ventilatory assistance during sleep. An alternative to a mechanical ventilator is Phrenic Nerve Pacing/diaphragm pacing.

*Q. Describe The Chemical Control Of Respiration :The 3 main chemical factors involved in regulation of respiration are arterial PCO2 ions concentration and PO2 1. Effects of PCO2 :- Normally arterial PCO2 is 40 mmHg. Rise in PCO2 stimulates respiration. So that more PCO2 is washed out and PCO2 comes back to normally. Rise in PCO2 from 40 mmHg. to 100 mmHg increase pulmonary ventilation eleven fold. On Mechanism of action :- Rise in PCO2 stimulates mainly by its action of central chemoreceptor’s situated in chemo sensitive area but it also stimulates peripheral. Chemoreceptor’s Chemo sensitive area is located bilaterally on ventral aspect of medulla medial to entry of ninth and tenth cranial nerves. It is connected to dorsal respiratory group of neurons. Rise in arterial pCO2 causes diffusion of more pCO2 into C.S.F. and medullary interstitial fluid. Here pCO2 Combines with H2O in pressure of carbonic anhydrase to from carbonic acid which splits in these fluids stimulates central chemo – receptors leading to increased pulmonary ventilation. The stimulatory effects of increased pCO2 and inhibitory effects of decreased pCO2 are reduced after few days due to adjustment in pH of C.S.F. 2. Effect of H+ ions :- Normally ph of arterial blood is 7.4 increases in H ion concentration stimulates respiration. Thus CO2 is and CO2 resulting in decrease in H ion conc. back to normal. Mechanism of action :- H ions have direct stimulating action on CSA and a less potent effect on peripheral chemoreceptor. However the effects are not as strong as rise in PCO2 because 1) H ions penetrate blood brain barrier slowly 2) resulting washout of CO2 decreases PCO2 which opposes stimulatory effect. 3. Effect of PO2 :- Normal arterial PO2 is 95 mm of Hg. Fall in PO2 stimulates respiration by its action through peripheral chemoreceptor’s but depresses respiration by direct action on respiratory centre. Peripheral chemoreceptor’s :are the chemo sensitive nerve endings of glossopharyngeal and vagus nerves situated in carotid and aortic bodies, whose sensitivity is modified by type I Glomus cells by releasing dopamine. These bodies have a very high blood supply and the cells and nerve endings are bathed in arterial blood. Fall in arterial PO2 (or rise in PCO2 and H conc.) stimulates these chemoreceptor’s, afferent impulses go to the respiratory centre which is stimulated and pulmonary ventilation increases. However, the affects of low pO2 on respiration are less potent because the resulting washout of CO2 ceases pCO2 and H ion conc., both of which oppose stimulation of respiration. Interaction of chemical factors :- 1. Low PO2 potentiates effects of increased PCO2 on respiration. 2 Increase in H ion conc. : Increases response of respiratory centre to increased PCO2 3. Rise in pCO2 potentiates the effect of low PO2 on respiration. Applied Physiology: - In conditions like diabetes mellitus or chronic renal failure, there is metabolic acidosis and respiration is stimulated. *Q. Describe The Structure of Respiratory Membrane. What Are The Factors Affecting Diffusion of Gases Through The Respiratory Membrane ?

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64 Respiratory membrane (or alvelocapillary membrane) is the membrane between air in the alveoli and blood in pulmonary capillaries across which gaseous exchange takes place. It is present lining the respiratory unit of lungs consisting of respiratory bronchioles, alveolar ducts, atria and alveolar sacs. It has a surface area of 70-80 sq. meters (both the lungs). It is extremely thin with an average thickness of 0.5 to 0.6 microns. Structure :- It is made up to 6 layers. From alveolar side these layers are 1) a thin layer of lining the alveoli and containing surfactant 2) Layer of thin, flat, squamous alveolar epithelial cells. 3) Basement membrane of alveolar epithelium 4) A thin layer of interstitial space between alveolar epithelium and capillary endothelium. 5) Basement membrane of capillary endothelium and 6) Pulmonary capillary endothelial cells layers. Normally, the volume of blood present in pulmonary capillaries is only 70 ml which is distributed over large area of respiratory membrane. It thus forms an extremely thin layer and facilitates exchange of gases. Factors affecting diffusion of gases :1) Pressure gradient of gases across the membrane :- pO2 of alveolar air is 104 mm Hg while that of deoxygenated pulmonary blood is 40 mmHg. Thus a pressure gradient of 64 mmHg exists across the membrane for O2 because of which O2 diffuses from alv. air to pulmonary blood. Similarly, pCO2 of pulmonary blood is 46 mmHg and that of alv. air is 40 mmHg. CO2 diffuses from pulmonary blood into the alveoli. The process of diffusion is complete in a fraction of a second. 2) Surface area of respiratory membrane :- Rate of diffusion is directly proportional to surface area more the area, more the rate of diffusion. Surface area increases during exercise acclimatization and decreases in collapse of lungs, partial removal of lungs, disease like tuberculosis which destroy the lungs etc. 3) Thickness of Respiratory membrane: - Rate of diffusion is inversely proportional to thickness. Thickness increases in alveolicapillary block conditions like lung fibrosis, congestion, edema etc. Decreasing the rate of diffusion of gases. 4) Solubility of gas in respiratory membrane :- Rate of diffusion is directly proportional to its solubility. CO2 is 25 times more soluble than O2 hence diffuse faster. 5) Molecular weight of the gas :- Diffusion rate is inversely proportional to square root. of mol. wt. of gas (CO2-44, O2-32) 6) Temperature: - Rate of diffusion is directly proportional to the temperature of gases, higher the temp. faster the diffusion. The overall diffusivity of a gas through the respiratory membrane is indicated by its diffusing capacity which is defined as the volume if gas that diffuses across the resp. membrane in one minute for each mm pressure gradient. Normally in resting state, the diffusing capacity for O2 is 21 ml/min/mmHg, while for CO2 it is 400-450 ml/min/mmHg. because the diffusion co-efficient of CO2 is 20 times that of O2. Applied physiology: - 1. At high altitudes, alveolar PO2 falls, hence pressure gradient and O2 diffusion is reduced. 2. In alveoli capillary block conditions extreme hypoxia occurs with little or no hyper apnea, because of high diffusion capacity for CO2. *Q. Define And Classify Hypoxia, Describe Hypoxic Hypoxia. Hypoxia is defined as condition characterized by generalized oxygen lack in the body at cellular level, that is the oxygen availability the cells is reduced (Hypo-less). Classification :Suggestions: facebook.com/asifpatel.ggmc

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1) Hypoxic hypoxia :- (arterial hypoxia) in which oxygen lack results from decrease in arterial PO2. 2) Anemic hypoxia: in which hypoxia of cells is due to decreases (absolute or functional) in quantity of hemoglobin. (Seen in all types of anemia’s, CO poisoning). 3) Stagnant or Circulatory hypoxia :- This type of hypoxia results from inadequate blood flow to the tissues (e.g. hypovolemic shock, CCF etc.) 4. Histotoxic hypoxia :- Due to failure of O2 utilization by the cells arising from damage to oxidative enzymes (e.g. in cyanide poisoning ) Hypoxic Hypoxia: A) Characteristic features :- 1) Arterial PO2 is reduced, hence tissues get less oxygen. 2) Atmospheric and alveolar PO2 may be normal or reduced (high altitude) 3) Hb content of blood is normal 4) Percentage saturation of Hb with O2 is endued because of low Po2 5) Therefore O2 content of blood is less. 6) Blood flow to tissues is normal. 7) AV oxygen difference is normal or reduced. 8) Oxygen utilization process by cells is normal. B) Conditions producing hypoxic hypoxia: 1. Conditions in which atmospheric PO2 is less- High altitudes. 2. Conditions causing defective pulmonary ventilation. a) depression of respiratory centre, by overdose of sedatives, anaesthetics, etc. b) paralyses of respiratory muscles e.g. polio, myasthenia gravis. c) obstruction in respiratory passage e.g. asthma, foreign body d) collapse of lungs e.g. pneumothorax e) reduced compliance of lungs e.g. pulmonary fibrosis, f) chest cage deformities. 3. Conditions which affect oxygenation of blood in lungs: a) alveolocapillary block e.g. pulmonary fibrosis, pulmonary edema. b) destruction of alveoli e.g. emphysema, TB c) reduced blood flow through lungs e.g. pulmonary congestion, infarction 4. Conditions producing AV shunts: e.g. patent ductus arteriosus, ventricular septal defect etc.

C) Effects of hypoxic hypoxia on body: 1) On respiratory System: Low arterial pO2 stimulates peripheral chemoreceptors in carotid and aortic bodies leading to increase in pulmonary ventilation. Initial increase in ventilation is only 65% due to inhibitory effect of CO2 washout. There is respiratory alkalosis due to washout of CO2 and oxygen-Hb dissociation curve shifts to left. Cheyne stokes respiration may be seen. If hypoxia is severe, cyanosis appears. Acute pulmonary edema may occur and can aggravate hypoxia. After 2-5 days, ventilation increases five folds 2) Effects on CVS: There is increase in heart rate, force of contraction and arterial pressure to compensate for hypoxia. There is constriction of cutaneous and splanchnic vessels. Prolonged myocardial hypoxia may lead to dilatation of heart and hypokinetic circulation. 3) Effect on nervous system- Depends upon severity of hypoxia. Mild hypoxia produces confusion, headache, irritability, drowsiness, insomnia etc. moderate hypoxia produces disorientation in time and space, loss of memory, failure of judgement, sluggish responses etc. Severe hypoxia causes twitchings, convulsions, coma and ultimately death. Acute cerebral edema is one of the serious complications of hypoxia. 4) Excretory system: Hypoxia stimulates production of erythropoietin. There is excretion of alkaline urine to correct alkalosis. 5) Digestive System: Motility and secretions are reduced. There is loss of appetite, constipation etc. *Q. Describe The Process of Oxygen Transport From Lungs to Tissues. Oxygen uptake in the lungs :- Normally the pO2 of alveolar air is 104 mmHg and that of deoxygenated blood in pulmonary capillaries is 40 mmHg. As a result of this pressure gradient, oxygen diffuses through alveolicapillary membrane into pulmonary blood, and gets dissolved in plasma. As more oxygen dissolves, pO2 starts rising and more oxygen enters the red blood cells. Transport of oxygen in blood from lungs to tissues occurs in 2 from:Suggestions: facebook.com/asifpatel.ggmc

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66 1) Transport in combination with Hemoglobin :- This mode accounts for 97% of O2 transported to the tissues oxygen combines with Hb to form a loose and reversible compound called oxyhemoglobin which is formed in lungs and dissociates in the tissues to release O2. Here, the O2 is carried in molecular form attached to one of the six covalent bonds of ferrous atom. One molecule of Hb carries 4 Molecules of oxygen. The rate of reaction between O2 and Hb increases as the second, third and fourth O2 molecules combine (Heme-Heme interaction). The Amount of O2 transported in combination with Hb depends upon 2 factors. a) Hb content of blood :- 1 gm of Hb, when fully saturated with O2, carries 1.34 ml O2 Hence greater the quantity of Hb, more is the O2 transported. b) Po2 of blood: - As Po2 of blood increases, percentage saturation of Hb with O2 goes on increasing and the oxygen content also increase. Oxygen – Hemoglobin dissociation Curve: -

Is plotted with pO2 on horizontal axis and percentage saturation of Hb with O2 on vertical axis. It is a sigmoid curve with flat upper part and steep slope in lower part. The flat upper part indicates that at pO2 range from 60 mmHg (hypoxia) to 200-300 mmHg (hyperbaric oxygen), Hb remains 90% 100% saturated, thus O2 uptake by Hb in lungs remains constant in spite of wide variation in alveolar pO2. The lower steep part of curve ensures that slight hypoxia of tissues will dissociate Hb to a greater extent, thereby increasing O2 release to the tissues. Normally in arterial blood with PO2 at 95 mmHg. Hb is 97% saturated with O2. Hence 100 ml of arterial blood containing 15 gm of Hb contains 19.4 ml of O2. As pO2 at tissues is 40mmHg, at which Hb is 75% saturated with O2 and has an O2 content of 14.4 ml per 100 ml blood, thus each 100 ml of arterial blood delivers 5 ml of O2 to the tissues. The ratio of O2 delivered to O2 content is called utilization co-efficient which is normally 25%. Increase in Pco2 reduces the affinity of Hb for O2 and shifts O2- Hb curve to right and below while decrease in PCo2 shits the curve above and to left. This is called Bohr Effect which helps O2 uptakes in lungs and O2 release to the tissues. Increase in H ion conc., rise in 2,3 DPG and rise in temp reduce the affinity and promote O2 delivery to tissues. 2) Transport of O2 in dissolved form: - Some O2 is also transported dissolved in fluids of blood. This mode accounts for 3% O2 transported to tissues. The amount of O2 in dissolved form depends upon PO2. 100 ml of arterial blood (Po2 -95 mmHg) contains 0.29 ml O2 while venous blood (Po2-40 mmHg) contains 0.12 ml of O2 in dissolved form. Thus 0.17 ml O2 is released to the tissues from dissolved form. Oxygen Diffusion Into Tissues Takes 2 Phases :-

1) From tissue capillary ( Po2 95 mmHg) to interstitial fluid (Po2-40 mmHg) and 2) then into the cell (PO2-32 mmHg). Applied Physiology :- O2 transported to the tissues increase in polycythemia and hyperbaric O2 treatment (dissolved form) and decreases in hypoxia and anemic hypoxia. *Q. Describe The Transport of Co2 Form Tissues To Lungs Suggestions: facebook.com/asifpatel.ggmc

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Co2 is taken up by blood in tissue capillaries and transported to the lungs where it is released into the alveoli. Co2 Uptake :- Co2 diffuses from the cells (PCO2 50 mmHg) into tissue fluid (Pco2 46 mmHg) and then into blood in tissue capillaries (Pco2 40 mmHg) along the pressure gradient. Transport in Blood :- In the blood, Co2 is transported in different forms as follows :

1) Transport in dissolved form :Some Co2, on entering the blood, gets dissolved in the fluids of blood. The amount of dissolved Co2 depends upon Pco2 of blood. In arterial blood (PCo2 40 mmHg) it is 2.4 ml/100 ml blood, while in venous blood (PCo2 46 mmHg) it is 2.7 ml/100 ml. That is, 100 ml of arterial blood picks 0.3 ml of dissolve Co2 in tissues and when this venous blood goes to the lungs, it releases 0.3 ml of Co2. It accounts for 7% of Co2 released into the lungs. 2) Transport As Bicarbonates :- Accounts for 70% of Co2 that is transported. In this mechanism, Co2 that enters RBCs combines with water to form H2CO3 the reaction being facilitated by carbonic anhydrase present in RBCs. H2CO3 then quickly dissociates to form H and HCO3 ions. H ions are buffered by Hb to form HHB. Some HCO3 ions combine with K ions to form KHCO3 and are transported in this form in the RBCs. Majority of the formed HCO3 ions diffuse out into plasma and combine with Na ions to form NaHCO3 which is transported in plasma. When HCO3 ions diffuse out of cells, chloride ions move into the cells to maintain electro neutrality. This is called Hamburger’s Chloride shift and is brought about by a protein called bicarbonate chloride carrier protein. When this venous blood reaches lungs, opposite changes take place. Oxygenation of Hb releases H ions which combine with HCO3 ions to form H2CO3 which the associates to form CO2 and H2O, Co2 diffuses out into the alveolar air. HCO3 ions from plasma enter the red cells continuing the above reaction and C1 ions diffuse out of cells. 3. Transport as Carbamino hemoglobin :- Some Co2 on entering the red cells combines with Hb to form a loose and reversible compound called carbamino Hb which is formed in the tissues at high Pco2 values (46 mmHg) and dissociates in the lungs at low PCo2 value (40 mmHg) and releases it Co2. Deoxygenated Hb has a greater affinity Co2 uptake by Hb in the tissues and Co2 release in the lungs. This mechanism accounts for 23% of Co2 transported. 4. Transport as carbambino proteins:- a small fraction of Co2 is transported in combination with plasma proteins. Quantity of Co2 Transported :- 100 ml of venous blood at Pco2 46 mmHg contains 52 ml of Co2. Similarly 100 ml of arterial blood at Pco2 40 mmHg contains 48 ml of Co2. Thus a net amount of 4 ml Co2 is transported by 100 my blood. Co2 Dissociation Curve: Is the curve plotted with total Co2 content of blood on vertical axis and Pco2 of blood on horizontal axis. It is almost linner in the physiological range. Rise in Po2 shift this curve downwards and to the right while fall in Po2 has opposite fall in Po2 has opposite effect. This is called Haldane effect which promotes Co2 release in lungs. Suggestions: facebook.com/asifpatel.ggmc

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68 Applied physiology :- Increase in Pco2 of blood is called hypercapnea and occurs in variety of conditions like asphyxia, alveolo-capillary block, etc.

*Q. Describe The Changes Taking Place In The Body During Acclimatization :Acclimatization or altitude tolerance is the process of adaptation of human body to the hypoxic conditions at high altitude. It consists of various compensatory changes taking place in the body to minimize the harmful effects of hypoxia ensuring adequate O2 delivery to the tissues and to increase work capacity of the individual. 1. Changes In Respiratory System :A) Increased pulmonary ventilation : results from action of hypoxia (Low PO2) on peripheral chemoreceptors. Initial stimulator effect is less because of breaking effect of low pCO2 which results from CO2 washout. After few days, this inhibitory effect disappears due to adjustment in pH of CSF and brain fluid, and ventilation increases 5 to 7 times. Increased ventilation increases alveolar pO2 and thus compensates hypoxia. B) Increased diffusing capacity for Oxygen (Do2): Results from a) increased pulmonary blood volume which distends pulmonary capillaries that are already open. b) opening up of capillaries that normally remain collapsed ( in apical parts of lungs) in response to pulmonary hypertension c) more stretching of alveoli due to greater depth of respiration. All these factors increase surface area of respiratory membrane and hence diffusing capacity for O2 from resting value of 21 ml/min/mm Hg to 60-65 ml/min/mm Hg. Thus O2 diffusion across alveolocapillary membrane increases. 2. Changes in blood: a) There is increase in RBC count (polycythemia) and content of blood . Hypoxia stimulates Kidney to produce erythropoietin which stimulates the bone marrow leading to formation of more RBCs. Increased Hb content (upto 22 gm%) increases the quantity of O2 transported to the tissues. b) Increased production of 2,3diphosphoglycerate in RBCs: Hypoxic conditions favour the production of 2,3 DPG in RBCs. This compound reduces the affinity of Hb for O2 (Shifts the Oxygen-Hb dissociation curve to right) and promotes release of O2 to tissues from Hb. (However, at high altitudes above 15000 ft, it also decreases O2 uptake by lungs). 3. Changes in Cardiovascular System: a) There is increase in cardiac output and blood volume by 20 to 30% initially, but with rise in Hb content, it comes back to normal. b) There is constriction of splanchnic and cutaneous vessels, thus diverting blood to vital organs. c) Pulmonary hypertension develops from vasoconstriction in response to hypoxia and the right ventricle shows hypertrophy to overcome pulmonary pressure. d) Chronic hypoxia leads to increased capillarity of active tissues, that is capillary density increases and this reduces the distance through which O2 has to diffuse to reach the tissues. 4. Changes in urine: Urine becomes alkaline due increased excretion of HCO3- ions to prevent respiratory alkalosis. 5. Cellular changes during acclimatization: Occur at altitudes between 13000 to 17000 feet. a)There is increase in the number of mitochondria. b) there is increase in enzyme cytochrome oxidase. These changes ensure efficient utilization O2 by cells. c) there is also increase in myoglobin content of muscle cells which can extract O2 in extreme hypoxic conditions: Natural acclimatization: is seen in permanent residents of high altitude and consists of 1) large size of chest 2) small body size 3) right ventricular hypertrophy 4) increased Hb content Applied Physiology : Sometimes the acclimatization fails to occur or disappear after few days leading to ventilatory depression or right ventricular failure, increased viscosity of blood etc. This is called chronic mountain sickness. Q. HERING BREUER REFLEX Named after Heinrich Hering and Joseph Breuer

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Hering Breuer inflation reflex: It is one of the reflex arising from peripheral receptors controlling. The receptors are the stretch receptors situated in smooth muscle layer of bronchii and bronchioles. When lungs are inflated, these receptors are stimulated and afferent impulses pass through the vagii to the dorsal respiratory group of neurons causing switch off of inspiratory ramp signal. Thus inspiration stops and expiration begins. Very large lung can cause apnea and strong stimulation of expiratory muscles. IMPORTANCE OF HB REFLEX : i) It limits phase of inspiration and hence increases rate of respiration. ii) It helps to maintain rhythmicity of respiration. iii) It acts as protective reflex and prevents excess lung inflation. iv) It is activated during exercise hyperapnoea and by limiting inspiration it reduces work of breathing, because the stretchability of lungs is less towards end of respiration. v) It also inhibits the apneustic centre. LIMITATION :This reflex is not activated till the inspiratory volume becomes 1 to 1.5 lit, hence it plays little role in control of resting respiration. Cutting or cooling of vagii abolishes this reflex. HERING BREUER DEFLATION REFLEX The receptors for this reflex are deflation receptors in lungs which are activated in condition that cause collapse of the lungs pneumothorax, pleural effusion. They send afferent impulses through the vagii and stimulate inspiration, thus air entry into uncollapsed lungs increase. This reflex is not active in normal quiet breathing. *Q.

Enumerate

Various

Pulmonary

Tests,

Describe

Any

Two

Them.

Pulmonary function tests are the tests carried out to assess the respiratory function of the lungs. Usefulness: 1) They are useful to study the degree of impairment of lung function resulting from diseases of lungs. 2) They help in diagnosis and prognosis of pulmonary disease. 3) To assess the risk for anesthesia and thoracic surgery. 4) Useful in industrial medicine to assess the degree of disability. 5) Useful for research purpose. Limitations :- 1) These testes need maximum co-operation of patients, hence have limited value in children and non-cooperative patients. 2) Specific diagnosis cannot be made from PFTs alone. 3) Detection of early lesions is difficult. 4) Site of lesion and type of lesion cannot be made out. Various pulmonary function tests are :-

A) Ventilator function tests :- a) Static lung volumes and capacities:- 1) Tidal volume 2) Inspiratory Reserve volume. 3) Expiratory Reserve Volume. 4) Residual Volume. 5) Inspiratory capacity. 6) Functional Residual capacity. 7) Vital capacity. 8) Total lung capacity.

b) Dynamic lung volumes and capacities :- 1) Forced vital capacity (Forced Expiratory Volume). 2) Maximum Breathing capacity (MVV). 3) Peak Expiratory flow rate (PEFR). 4) Maximum mid Expiratory flow Rate (MMEFR). 5) Resting minute Volume. 6) Walking Ventilation. 7) Ventilator Index. C) Other ventilatory function tests:- like measurement of 1. Anatomical dead space. 2. Lung compliance 3. Blood gas analysis. B) Tests for diffusion: Measurement of diffusing capacity of lungs for O2 (transfer factor). Suggestions: facebook.com/asifpatel.ggmc

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70 C) Tests for Perfusion: 1) Measurement of Right ventricular output 2) determination of ventilation- Perfusion ratio. 3) Study of pulmonary circulation pressures by cardiac catheterization. D) Miscellaneous PFTs:- 1) Sputum examination 2) Screening and X-ray of chest 3) Bronchography 4) Bronchoscopy 5) CT scan 6) Lung billowy etc.

1. Vital capacity :- It is the maximum volume of air exhaled by forceful expiration after maximal inspiration. Normal value 4.2 to 4.6 liters (Indian males- 3.6 to 4.00 lit, females- 3.3 to 3.6 lit) It is a combination of tidal volume (Operatory reserve volume (TRV) and Expiratory reserve volume (ERV). Measurement :- By using simplistic meter, electronic spirometer or expirograph. The subject is first asked to Inhale maximally, and then to exhale forcefully and the volume of exhaled air 19 measured.

Physiological Variations in Vital Capacity :- 1) Age:- Low in the newborn, increase with age and decreases in

old age. 2) Sex- more in males than females. 3) Surfaces area: - VC in directly proportional to surface area. 4) Height: - More VC in tall persons. 5) Posture: - More VC in erect posture than in lying. 6) Pregnancy: - VC is reducing decreased in 1) have more VC. Pathological Variations :- VC is decreased in 1) Paralysis of respiratory muscles e.g. Polio, myasthenia gravis. 2) reduced expansibility of lungs e.g. pulmonary congestion, fibrosis, collapse of lungs.3) Chest cage deformities. 4) Tense ascetic or large abdominal tumor.

Importance of vital Capacity: - 1) It is an important ventilatory function test that indicates the maximum volume of air which can be moved out of lungs. It depends on a) Healthy state of lungs and b) strength of respiratory muscles 2) It indicates progress of fibrotic diseases. 3) It is useful in prognosis of conditions like left ventricular failure in which VC increases after proper treatment due to decrease in pulmonary congestion. 2. Forced Expiratory Volume or Timed Vital Capacity:-

It is the volume of air exhaled by forcible expiation in a definite time (one, two or three seconds) and expressed as percentage of vital capacity. If a person having vital capacity 4 its, exhales 3 lit, of air in 1 sec, then his FEV1= ¾ x100= 75 % . Normal Values: - FEV1- 83 % to 87 %

Measurement: - FEV can be measured by using spirometer or expirograph. The subject is first asked to inhale maximally and hen exhale rapidly and forcefully. The expiration is recorded on a fast moving kymograph and the amount of air exhaled in 1, 2 or 3 secs. Is capacity to give FEV1, FEV2 and FEV3 respectively?

Significance :- FEV indicates the ability to exhale forcefully which depends upon air way resistance and strength of expiratory muscles.

Clinical Importance :- 1. FEV is reduced in obstructive type of diseases like bronchial asthma and emphysema in which airway resistance in increased. 2. It helps to differentiate obstructive diseases (FEV1 reduced, VC normal) from Restrictive disease like kyphosis (FEV1 normal) reduced. Surfactant:

Is the surface tension lowering agent present in alveolar fluid. It was first discovered by prattle in 1956. Suggestions: facebook.com/asifpatel.ggmc

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Chemistry: - It is a mixture of chemical containing- 1. Dipamitoyl phosphatidyl Choline (DPPC) which is the main chemical. 2. Surfactant apoproteins. 3. Calcium ions. These help in spreading the DPPC.

Secretion:- It is secreted by type II alveolar cells (granular pneumocytes) which are cubical in shape and contain multilamellar bodies. These cells start secreting surfactant in third trimester of pregnancy. The secretion is stimulated by hormones like glucocorticoids and thyroxine and suppressed in diabetic mothers.

Actions of Surfactant :- 1. It reduces the surface tension of fluid lining the alveoli and decreases their collapsing tendency: - The DPPC is a phospholipids molecule containing hydrophilic and hydrophobic groups. These molecules align themselves at the air liquid interface of alveolar fluid so that their hydrophilic portions remain in alveolar fluid and hydrophobic portions project towards air. Thus they reduce intermolecular attraction forces and surface tension from 50 dynes to 5 to 30 dynes /cm 2. It stabilizes the alveoli.

According to Laplace’s law, smaller alveoli have greater collapsing tendency than larger alveoli. Surfactant gets concentrated in smaller alveoli and decreases their surface tension to a greater extent, thus reducing their collapsing tendency. 3. It prevents pulmonary edema :- Force created by surface tension of fluid lining the alveoli tries to draw surfactant reduces this force and prevents occurrence of edema. 4) It reduces work of breathing by decreasing the recoil tendency of alveoli. 5) It lowers collapsing tendency of alveoli during normal expiration (FRC) as they become smaller. *Q. Respiratory Distress Syndrome (Hyaline Membrane Disease)

It is a condition that results from failure of secretion of surfactant by type II alveolar cells. It is seen in new born babies, especially in the premature babies because the secretion of surfactant occurs during 2-3 months of pregnancy. Babies of diabetic mothers are also prone to develop this condition.

Pathophysiology: - Normally the surfactant reduces the surface tension of fluid lining the alveoli and prevents collapse of alveoli. It also stabilizes the sizes of alveoli and prevents occurrence of pulmonary edema. Due to loss of these functions in RDS, surface tension of alveolar fluid remains high causing collapse (atelectasis) in some parts of lungs. Lungs also resist expansion. (Low compliance) due to high recoil tendency. Moreover in premature babies, the alveoli are still smaller and according to Laplace’s law, smaller alveoli have greater collapsing tendency. Clinical features: - New born baby has great difficulty in breathing (distress) especially during inspiration. Work of breathing is increased and accessory muscles of respiration are active. Baby may develop cyanosis and, if severe, may die of asphyxia. If the lungs are examined under microscope, the alveoli are seen filled with edema fluid giving an appearance of a hyaline membrane. (hence called hyaline membrane disease). Treatment: - . Administration of synthetic surfactant till normal synthesis of surfactant begins. 2. O2 administration if necessary. 3. Administration of glucocorticoids also facilitates synthesis of surfactant. Prevention: - By administration of glucocorticoids to mother in threatened premature labour. Suggestions: facebook.com/asifpatel.ggmc

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72 Peripheral Chemo receptors :- Are the receptors sensitive to chemical changes and situated peripherally, i.e. outside the nervous system. They are present in Carotid and Aortic bodies.

Functional anatomy: - Carotid bodies are small round encapsulated situated in bifurcation of common carotid artery. Afferent nerve fibers arising from these bodies pass through Herring’s nerve and then through glossopharyngeal nerve end tractus solitaries to end in dorsal respiratory group of neurons and also in Vasomotor centre. Aortic bodes are similar, but situated along the arch of aorta. Their afferents pass through Aortic nerve and vagus to terminate in DRG and VMC. Histologically these bodies contain 2 types of glandular cells, type I called Glomus cells and type II are glial cells. In between these cells are the nerve ending of afferent fibers which themselves act as chemoreceptors. The sensitivity of these nerve endings is modified by releasing dopamine or nor adrenaline by the glomus cells. One of the peculiarities of these bodies is that they have a very high blood flow. Stimuli for chemoreceptors :1) The principal stimulus is hypoxia or low PO2. Therefore any conditions that produces hypoxic hypoxia (high altitude, lung diseases, respiratory muscle paralysis, AV shunts etc.) will stimulate these receptors leading to strong stimulation of respiration and increased pulmonary ventilation, which will compensate for hypoxia. 2. Fall in arterial blood pressure: The blood flow to these bodies decreases and stimulates the chemoreceptors which in turn, cause strong activation of vasomotor centre. Vasoconstriction and rise of arterial pressure back to normal.

3. Increases in PCO2 and H+ ion concentration: - Also stimulates peripheral chemoreceptors but their effects are more pronounced on central chemoreceptor’s.

Drawbacks : Peripheral chemoreceptors are not stimulated in conditions like anemia or CO poisoning where PO2 remains normal. Q. Dysbarism :- Decompression Sickness – Caisson Disease :-

This is a condition that is seen in divers who work at great depths of the sea for long periods and when they come rapidly to the surface .Genesis:- When a diver is working at the depth of sea, he is exposed to high barometric pressure (barometric pressure rises by 1 atmosphere for every 33 feet descent) and therefore he has to breath air or any other gas at high pressure to prevent collapse of chest. If he breathes air (80% nitrogen) at high pressure. large amounts of N2 gets dissolved in his body fluids especially in the lipids of nervous system because N2 is more soluble in lipids than in water. Excess N2 in brain neurons produces alcohol like effects called Nitrogen narcosis. When this diver rapidly comes to the surface of the sea, his body is suddenly decompressed. Therefore the dissolved N2 become less soluble and comes out of solution in the form of bubbles in the tissues (similar to opening of a soda water bottle) producing, various symptoms.

Manifestations :- 1) Acute pain in bones and joints (especially elbow) called bans. It is due to N2 bubbles in periosteum. 2) Sensation of choking (chokes) due to bubbles in pulmonary capillaries.

3) Tingling, numbness and loss of sensation (bubbles in myelin sheath) 4) Paralysis of muscles. 5. Angina pectoris or cardiac arrhythmias (bubbles in coronaries) 6. Sometimes serious complications like coma, respiratory failure, permanent mental damage etc. are seen. Treatment :- Prompt recompression of the subject in a compression chamber followed by gradual stepwise decompression. Oxygen administration if required.

Prevention :- 1. Gradual stage wise ascent with some time spent at each stage. 2. By use of Helium-oxygen mixture instead of air. Helium is less soluble and more diffusible. Intrapleural Pressure: - Is the pressure in the pleural cavity which is a potential space between parietal and visceral pleura. Suggestions: facebook.com/asifpatel.ggmc

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Normal Value:- Normally in the end expiratory state it is 5 cm of H2O (subatmospheric). During normal inspiration it becomes- 7.5 cm of H2O. While in forced inspiration it can become – 20 to – 25 cm of H2O. There is a vertical gradient of pressure in pleural cavity, more negative towards apices and less negative towards bases of lungs. Cause of Negativity :- The intrapleural negativity is due to 2 factors, 1) the visceral pleura tries to move inwards become of inward recoil of lungs while parietal pleura is pulled but wards by outward recoil of chest wall. 2. Absorption of tissue fluid into the lymphatics creates a suction force which contributes to negativity. Measurement:- Intrapleural pressure can be measured by a direct method- a needle is inserted into the pleural cavity intraoesophagal rubber billion which faithfully records changes in pleural pressure

Importance of Intrapleural Pressure :- 1.The negative intrapleural pressure keeps the two layers of pleura in contact with each other wall. As the chest expands, lungs also expand. 2. It exerts outwards pull on alveoli keeping them expanded and prevents their collapse. 3. It also keeps small airways expanded. This is necessary because they do not have cartilage in their walls, loss of pleural negativity closes these bronchioles (Closing volume) 4. During inspiration, pleural and hence mediastinal pressure become more negative which has a sucking effect on blood from abdominal veins. It thus facilitates venous return (Respiratory pump). Applied aspects :- In conditions like pneumothorax or pleural effusion, intrapleural negativity is lost and there is collapse of lungs. Q. Periodic Breathing

It is an abnormal type of cyclical breathing is which there alternate phases of hyperpnoea and apnea. There are 2 types of periodic breathing: 2) Cheyne Stoke’s Breathing :- In this type of breathing there are alternate phases of hyperventilation and apnea and there is gradual transition from one phase to next. Conditions:- 1. Congestive cardiac failure, especially, left ventricular failure. 2. Hypoxia occurring at high altitudes. 3. Head injury with cerebral hemorrhage. 4. Uremia. 5. Increased intracranial pressure. 5. Normally in children in deep sleep and in adults after hyperventilation. Mechanisms of Cheyne Stroke's breathing:

1. Prolonged circulation time from lungs to brain :- During phase of apnea PCO2 in pulmonary blood rises, but it takes a longer time to reach and stimulate respiratory centre.

In the mean while PCO2 continues to rise and when this blood ultimately reaches, respiratory centre, it causes strong stimulation and hyperventilation. Hyperventilation causes excess washout of CO2, fall in pCO2 and apnoea. Thus the cyclical pattern continues. There are marked fluctuation in arterial pO2 and pCo2. in this type of breathing. Here the respiratory control mechanism oscillates because the negative feedback loop from lungs to brain is abnormally long. Normally such oscillations damped by the storage capacity of blood and resp. neurons for O2 and CO2. 2. Increased Sensitivity (increased feedback gain) of respiratory centre :- Here, the resp. neurons become highly sensitive (irritable) due to damage or infection. Therefore a slight rise of pCO2 causes strong stimulation and slight fall in pCO2 causes strong inhibition of resp. Centre producing periodic breathing. B) Biots Breathing :- Here, there are periods of normal or deep breathing interrupted by periods of apnoea, but the transition from one phase to another is abrupt. It is seen in conditions of severe brain damage like concussion, meningitis and is due to irritability of resp. neurons. *Q. Ventilation Perfusion Ratio : Suggestions: facebook.com/asifpatel.ggmc

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74 Def :- It is the ratio that expresses the balance between alveolar ventilation and perfusion. It is expressed as VA/Q. The normal value of V.P. ratio for entire lungs is 0.8 (Alveolar ventilation/min is 4.2 L, Pulmonary blood flow is 5 L/ min). At normal V.P. ratio, there is optimum exchange of gases in the alveoli and alveolar air has Po2 104 mmHg and PCo2 40 mmHg.

Variations :- 1) V.P. ratio less than normal :- Will arise in those situations where alveolar ventilation decreases eg. Obstructing in resp. Tract. Here sufficient air is not available to oxygenate all the blood flowing through pulmonary capillary, hence some fraction of pulmonary blood passes deoxygenated to the left side of heart. This is called Shunted blood. If V.P. ratio is 0, alveolar air equilibrates with venous blood in pulmonary capillaries and acquires Po2 40 mmHg and Pco2 46 mmHg. 2) V.P. ratio more than normal: - Occurs when alveolar ventilation is more than normal (or pulmonary capillary flow less). Therefore some air remains

excess in the alveoli and is not utilized for gaseous exchange. Such volume of air is called wasted ventilation or alveolar dead space. If V.P. ratio becomes infinity (no perfusion), then alveolar air becomes humidified atmospheric air with Po2- 149 mmHg and PCo2 0 mmHg. Ventilation Perfusion curve: - Is the curve plotted with Po2 of alveolar air on horizontal axis and PCo2 on vertical axis. A sample of alveolar air can be collected from the subject, its Po2 & pO2 measured and plotted on this curve will indicate qualitative and quantitative variations in V.P. ratio. Applied Aspects :- 1. ratio is decreased in obstructive conditions like asthma, foreign bodies in bronchi and in hypoventilatory disorders like myasthenia, poliomyelitis etc. causing shunting of large quantities of blood. 2) It is increased in disease destroying alveolar walls like tuberculosis, emphysema or in pulmonary embolism leading to wasted ventilation. 3. Normally also V.P. ratio is more in apical parts of lungs (dead space) and less in basal parts (shunt). *Q. Respiratory Dead Space:

Def: - It is the volume of air present in respiratory tract which cannot be utilized (or which is not available) for gaseous exchange. There are 2 types of dead space:-

1) Anatomical dead space :- is the volume of air present in that part of respiratory tract where gas exchange is not possible because of anatomical reason i.e. parts of respiratory tract like upper resp. tract, trachea, bronchi and bronchioles which are not lined by respiratory membrane. Its normal value is 150 ml or 1 ml/ Hb body wt. Therefore when a person inhales 500 ml tidal volume, only 350 ml air enter alveoli. Measurement:- The subject takes a breath of pure O2 and the instantaneous N2 conc. of exhaled air and volume of exhaled air are measured. Then a curve is plotted with N2 conc. on vertical from N2 indicates anatomic dead space and is calculated by. Formula :-

Anatomical dead space Area containing O2/Total area of curve x vol of exp. air.

2. Physiologic dead space or 'total' dead space :- Includes anatomical dead space and the volume of air in the alveoli which not available (or utilized) for gaseous exchange. Such volume is called alveolar dead space. Measurement:- Physiologic dead space is calculated by measuring PCO2 of expired air (pEco2), PCo2 of alveolar air (PAco2) tidal volume (VT) and by applying Bohr’s equation :-

PECO2 x VT = PACO2 x (VT-VD) + PICO2 x VD

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Applied aspects :- Alveolar dead space and therefore physiologic dead space increases in conditions where VP ratio is more than normal. It can occur in condition which reduce perfusion like pulmonary congestion or embolism or in conditions which cause hyperventilation of alveoli like emphysema. Function Residual Capacity (FRC) :-

Def:- FRC is the volume or air present in lungs at the end of tidal expiration. Its normal value is 2300 to 2500 ml (1900- 2000 ml in Indians). It is a combination of Expiratory Reserve Volume and Residual Volume Measurement of FRC:- 1) Helium dilution method: Aspirometer of known volume (VT) is filled with a mixture of Helium and air and conc. of helium noted (C1). The subject is asked to breathe into this spirometer starting at end expiratory position (FRC). After few minutes, helium gets diluted in VS and FRC and it final conc. noted (CF) the degree of dilution depending upon FRC. The FRC is calculated as:FRC= VS (CI-CF) CF

2) N2 washout method :- In this method, all the N2 present in FRC is washed out by breathing pure O2 and its volume measured. This N2 form 80% of FRC, thus FRC can be calculated. 3) Whole body plethysmography. Importance of FRC:- FRC is the volume of air in the lungs available for gas exchange in between the breaths. Its fairly high value (2.3L) and relatively small dilution by inspired air, allows it to act as buffer preventing large change is alveolar pO2 with each breath. It thus prevents marked fluctuations in arterial pO2 and pCO2 between the respirations.

Clinically, FRC is decreased in conditions like collapse of lungs. pulmonary fibrosis etc. end is increased in emphysema. *Q. Lungs Compliance :-

Defn :- Lung compliance is the change in lung volume per unit change in transpulmonary pressure. It is expressed as V/ P it normal value is 0.2 Lit/ cm of H2O .

Measurement:- change in lung volume is measured on spirometer or expirograph and change in transpulmonary (pleural pressure-alv pressure) pressure is measured by an intraoesophageal balloon. Subject is asked to inspire and expire tidal volume in steps of 100 ml and at each stage transpulmonary pressure noted. Then a pressure volume curve is plotted, the slope of the curve indicates lung compliance. There are 3 types of lung compliance: 1. Static lung compliance recorded with breathing stopped. 2. Dynamic compliance :- Recorded while breathing. 3. Specific compliance :- Which is compliance per unit volume of lung, usually dynamic compliance is less then static compliance.

Significance of lung compliance : compliance value indicates the dispensability of lungs or stretchability of lungs. It is less at low lungs volume and increases during exercise because of greater stretching of alveoli. It depends upon elastic recoil of lungs, airway resistance, amount of surfactant etc. Applied Aspects: Lung compliance is decreased in following conditions. Pulmonary congestion, pulmonary edema, pulmonary fibrosis, hyaline membrane disease (due to deficiency of surfactant) and extrapulmonary Suggestions: facebook.com/asifpatel.ggmc

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76 conditions like kyphoscoliosis. In these conditions, work done by respiratory muscles to bring about expansion of lungs (compliance work) increases. On the other hands compliance is increased in emphysema due to destruction of elastic fibers. Q. Maximum Ventilatory Volume (MVV) or Maximum Breathing Capacity (MBC) :-

Def :- It is the maximum volume of air that can be breathed in or out of the lungs in one minute by maximum respiratory efforts. Normal Value :- 100 to L/min in males and 80 to 100 L/min in females. Measurement :- 1. By using spirometer :- The subject is asked to breath rapidly and forcefully into the spirometer for 15 seconds, and the volume of air moved in or out of the lungs noted. The value is multiplied by 4 to get MVV. The procedure is carried out only for 15 seconds because. 1. It is an exhaustive procedure especially for old and sick person. 2. Washout of CO2 causer visual blackout, alkalosis and can cause tetany. 2. By using Douglas bag :- The subject is asked to breath rapidly and forcefully for 15 seconds and the expired air is collected in Douglas bag through an expiratory value. Its volume is noted and multiplied by 4 to get MVV. Importance of MVV :- 1. MVV indicates maximum ventilator power of the subject. It is one of the important pulmonary function tests and its value depends upon healthy state of lungs and is also on strength of respiratory muscles. It depends upon expansibility (compliance) of lungs and airway resistance.

2. MVV indicates breathing reserve (MVV-RMV) :- of subject and is useful in calculation of dysphonic index. Applied aspects :- MVV is decreased in various conditions like weakness of respiratory muscles (polio, myasthenia), fibrosis of lungs, bronchial asthma, chest cage deformities, collapse of the lungs, pulmonary congestion and pulmonary edema. Q. Dyspnoea :-

Defn.: Dyspnoea is a conscious unpleasant sensations of difficulty in breathing. Also called ‘Distressed’ or ‘Air hunger’

Factors causing development of dyspnoea :- 1. Any factor that causes strong stimulation of respiratory centre, especially, hypercapnea. Hypoxia and increase in H ion conc. can also lead to dyspnoea. 2. Any factor that increases work done by the respiratory muscles(work of breathing) to provide adequate ventilation. 3. Psychogenic factor, that is, when a person fears that he will not get sufficient air, especially, in a crowded room (neurogenic or emotional, dyspnoea) 4. Stimulation of J receptors and lung irritation receptors produces dyspnoea. 5. Decrease in vital capacity and breathing reserve produces dyspnoea. Conditions :- Physiological dyspnoea occurs in severe exercise while pathologically dyspnoea occurs in many conditions like :- 1.Cardiac dyspnoea due to pulmonary congestion seen in mitral stenosis, left ventricular failure. 2. Respiratory conditions: - asthma, pulmonary fibrosis, collapses of lungs, pulmonary edema, hyaline membrane disease etc. 3. Conditions that interfere with movements of diaphragm (tense ascetic) or chest wall compression 4. Metabolic acidosis conditions like diabetes mellitus etc. Dyspnoeic point: - The state of increased ventilation at which the person starts feeling breathless is called dyspnoeic point. Dyspnoeic index (Breathing Reserve Ratio ) : It is the ratio of breathing reserve (MVV-RMV0 to maximum Ventilatory volume (MVV) expressed as percent. Normally it is 100-6/10x100= 94% when it becomes less than 60%, the person develops dyspnoea. Thus when breathing reserve becomes low, person develops dyspnoea. Q. Asphyxia:-

Def:- It is an acute conditions in which there is simultaneous rise in blood PCo2(hyper apnea) Suggestions: facebook.com/asifpatel.ggmc GGMC MUMBAI

Conditions Producing asphyxia :- A) Acute asphyxia is seen in

1. Strangulation, hanging 2. Foreign body in trachea 3. Laryngeal spasm (tenancy, anaphylactic shock) 4. Diphtheria 5. Compression of chest 6. Collapse of lungs (pneumothorax) 7. Paralysis of diaphragm (spinal cord injury).

B) Chronic asphyxia :- is seen in emphysema, alveolocapillary block conditions, hypoventilation block conditions, hypoventilation and circulatory deficiency conditions. Manifestations of acute hypoxia: - are divided into 3 stages: 1. Stage I or stage of hyperpnoea :- There is strong stimulation of respiration and violent resp. efforts, expiratory movements are more pronounced. There is dyspoea. These effects are due to increased PCo2 acting on resp. centre. There is loss of consciousness due to hypoxia of brain. This stage lasts for 1 minute. 2. Stage II or stage of central excitation :- There is sharp increase in heart rate, blood pressure and widespread vasoconstriction with release of large amounts of catecholamine’s into the circulation. All these effect body due to hypoxia stimulation of vasomotor centre:- Entire body goes into convulsions due to action of increased PCo2 on neurons of the brain. Maturation and defection may occur acidosis may occur due to convulsion. This stage lasts for 1-2 minutes. 3. Stage III or stage of central depression:-

Respiration becomes slower and there is spasmodic inspiration or gashing. There is dilatation of pupils and loss of all reflexes. The duration between the aspiratory gaps goes on increasing and ultimately respiration stops and death occurs. All these effects are due to irreversible damage to vital central of brain caused by hypoxia (mainly) and by hypercapnea. This stage lasts for about 3 minute. Effects of G Forces on the Body :-

G forces are the centrifugal acceleratory forces acting on the body of an aviator when he takes a turn. This forces is directly proportional to mass of the body, square of velocity of airplane and inversely proportional to radius of turn, sharper the turn, stronger the force. When this force is equal to pressure exerted by the body due to gravity it is called l. G. force. Similarly when the force acts in head to foot direction, it is called + G and if in opposite direction, G Effects of G. on the body :- 1. In positive G, blood is centrifuged increases tremendously causing their distension and pooling of blood in lower part o body. 2. Therefore there is decrease in venous return and cardiac output. 3. There is fall in systolic and diastolic pressure which is partly compensated by bar receptor, reflexes. 4. When the force exceeds 5 G, blood to the retina decrease and three is temporary loss of vision called Black out. 5.At higher G values, blood flow to pain decreases leading to loss of consciousness. Continued acceleration my cause death. 6. A very high force of 20 G can cause fracture of vertebrae. Effects of Negative G :- In this condition, blood is centrifuged towards upper part of the body. 1. Increased venous return increases cardiac output and arterial pressure. There may be reflex bradycardia. 2. A force of 4 to 5 G causes hyperemia of brain and mild cerebral edema causing mental confusion. 3. If the fore exceeds -10 to -12G, there is sever rise in pressure in cerebral vessels, however, they do not rupture because of cushioning effect of CSF. 4. There is severe hyperemia of retina producing transient loss of vision called Red out Protection from G forces: - By adopting suitable position like leaning forwards with knees flexed and lags drawn up. Or lying transverse to axis o acceleration. 2. By use of Anti G suits. Effects of Weightlessness In Space :-

Weightlessness in space is not cut to absolute lack of gravity, but the gravity force is very minimal and neutralized by lack of resistance to movement in space. Because of weightlessness, astronauts freely float in the spacecraft and develop following effects. Immediate effects : 1. Motion sickness nausea and vomiting because of disorientation, conflicting visual scenes and lack of gravitational signals. 2. There is. Suggestions: facebook.com/asifpatel.ggmc GGMC MUMBAI

78 Translocation:- of blood towards upper part of body due to lack of gravity and loss of hydrostatic pressure. 3. There is decrease in physical activity of person and decreases in force of contraction of muscles :- Long Term effects:- 4. Decrease in blood of heart distends them leading to suppression of ADH secretion and increased urine volume. Loss of ECF therefore decrease blood volume by 15% 5. Decreased blood volume decreases blood volume return, cardiac output and blood pressure. 6. There is decrease in erythropoietin level in blood leading to fall in REC count and PCY. 7. Muscle tones is reduced and movements becomes clumsy. This effect is particularly seen in antigravity muscle. Work done by muscles decreases due to lack of resistance. Muscle size in also reduced. 8. There is osteoporosis or demineralization of bones. This is similar to disuse atrophy, causing mobilization of Ca and PO4 from banes. Bones become brittle and can be easily fractured. Ca excretion in urine 10 increased. Most of these effects disappear after few days, but effects on bones and muscles persist and they can be minimized by isometric exercises abroad the spacecraft. Cyanosis:-

Def:- Cyanosis is a condition characterized diffuse blue dusky discoloration of skin and mocus membrane.

Cause :- It is seen when the concentration of deoxygenated Hb has dark blue purple color. Common sites of cyanosis :-Lips, tongue, tip of the nose, nail bed, heels (in infants) and ear lobule. Types of cyanosis: - 1. Central cyanosis which results from defective oxygenation of blood in the lungs. 2. Peripheral cyanosis which occurs in peripheral circulatory failure.

Factors affecting cyanosis :- 1. Quantity of deoxygenated Hb should be more than 5% gram to produce cyanosis. 2. Total quantity of Hb in Blood: cyanosis is more likely in a person with polycythemia than in anemia, because in anemia Hb content is less hence less chance of reduced Hb exceeding 5 gm%. Moreover, polycythemia is associated with increases viscosity of blood predisposing to stagnation. 3. Rate of blood flow through skin:- Sluggish blood flow permits greater O2 removal by the tissues causing rise in reduced Hb content and cyanosis. 4. Pigmentation and thickness of skin:- Cyanosis is not easily seen in dark persons or in areas where the skin is thick. Significance of cyanosis: - Cyanosis is an important sign of cardio respiratory or peripheral circulatory insufficiency. Conditions producing cyanosis :-

A) Conditions causing hypoxic hypoxia 1) High altitudes

2) Paralysis of resp. muscles (polio, myasthenia) 3) Airway obstruction (asthma, foreign body, strangulation) 4) Lung diseases (tuberculosis, emphysema) 5) Alveolo capillary block (pulmonary fibrosis, congestion). 6) AV shunts (VSD, PDA). B) Conditions causing stagnant hypoxia:-

1) Congestive cardiac failure. 2. exposure to cold 3.Vensous obstruction.

Treatment :- 1. O2 administration for central cyanosis. 2. Treatment of underlying disease. Methamo globinemia also produces bluish discoloration similar to cyanosis. Effects of Hyperbaric Oxygen :Suggestions: facebook.com/asifpatel.ggmc

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Def:- Hyperbaric O2 is the administration of oxygen at pressures more than one atmosphere. Usually in clinical practice, oxygen at 2.5 to 2 atmospheres is used. It is administrated by gas mask or by tracheal intubation. Indications :- 1.Carbon monoxide poisoning to displace co from Hb0 2. Gas gangrene- to kill anaerobic. 3. Surgery in congenital heart disease. 4. Cyanide poisoning.

Effects on the body:- 1. Administration of hyperbaric O2 increases alveolar Po2 and hence the amount of

dissolved O2 rise to 4-5 ml/100 blood. The tissues get their O2 from dissolved blood itself, hence HbO2 does not dissociate and hence carbamino Hb cannot be formed. Therefore Co2 starts rising in the tissues. 2. Rise in cerebral arterial Po2 causes cerebral vasoconstriction. 3. Increased Po2 in arterial blood causes constriction of retinal vessels leading to formation of opaque vascular tissue behind the lens called Retrolental fibroplasia and blindness. 4. High Po2 can produce pulmonary edema. 5. Chronic O2 administration can cause development of cysts in the lungs (bronochopulmoary dysplasia). 6. At cellular level, it forms superoxide anion (O2). It also inactivates cellular enzymes in Kreb’s cycle containing sulfhydril groups leading to decreased synthesis of ATP. 7. Clinically, it produces symptoms like irritation, congestion of resp. tract mucus membrane, muscular twitchings, tinnitus and sometimes convulsions and coma.

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GASTRO-INTESTINAL

Chapter 6

PHYSIOLOGY

*Q. DESCRIBE THE REGULATION OF SALIVARY SECRETIONS.

Saliva is thin watery fluid secreted by 3 pairs of salivary glands. 1)Parotid glands (Secreted 25% of total Saliva) (2)Submandibular glands (70%) and (3) Sublingual glands (5%). REGULATION:- Regulation of Salivary secretion is entirely a reflex process mediated by superior and inferior salivatory nuclei. There are 3 types of stimuli which can cause secretion of saliva: 1)PRESENCE OF FOOD IN MOUTH:- Causes stimulation of tactile receptors in mouth, tongue, pharynx and also of taste buds. Afferent impulses are carried through lingual, glossopharyngeal and vagus nerves to sup. and inf. salivatory nuclei situated in reticular formation at the junction of Pons and medulla. These nuclei then send efferent secretomotor impulses to the salivary glands leading to copious secretion of saliva by the acinar cells (5 to 8 ml/min). Secreted saliva helps in formation of food bolus and also act as lubricant. Efferent from sup. salivary nucleus pass through lingual, chorda tympani and then through submandibular ganglion to supply submandibular and sublingual glands, while those from inf. Salivary nucleus pass through glossopharyngeal, its tympanic branch and otic ganglion to supply parotid glands. This secretion of saliva occurring in response to food in mouth is an unconditioned reflex and the quantity of saliva secreted varies with the types of substances, for e.g. smooth substances cause secretion of more saliva. 2. SIGHT, SMELL OR THOUGHT OF FOOD: Also causes secretion of saliva (watering of mouth). Here, the impulses originate in higher centres of brain such as appetite centre of hypothalamus or visual or small centres of cerebral cortex and end on salivary nuclei stimulating them. Therefore favourite and appetizing foods cause more salivation than other foods. This secretion of saliva in response to sight, smell or thought of food is a condition reflex and is always acquired. 3. STIMULI ARISING FROM OTHER PARTS OF GASTROINTESTINAL TRACT: Irritation of mucosa of oesophagus causes excess salivary secretion – oesophagosalivary reflex. Irritation or distention of stomach also stimulates salivary secretion- gastrosalivary reflex. Secreted saliva helps in diluting and neutralizing irritant substance. These reflexes are unconditioned reflexes and their afferents pass through the vagus to the salivary nuclei. Suggestions: facebook.com/asifpatel.ggmc

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SPONTANEOUS OR RESTING SECRETION:-Small quantity of saliva is continuously secreted by salivary glands (0.5 ml/min)even in resting state. It is due to release of small amounts of acetyl choline by nerve endings in salivary glands .The secreted saliva keeps the mouth moist and helps in speech. OTHER FACTORS:-1.Stimulation of sympathetic fibers supplying salivary glands increases salivary secretion. 2.Vasodilatation in salivary glands, either due to release of VIP(Vasoactive intestinal peptide) or due to formation of bradykinin, is associated with increased salivary secretion. Applied Physiology:- 1.Salivary secretion is inhibited by parasympatholytic drugs like atropine during surgery. 2.Salivation occurring before vomiting is gastrosalivary reflex. 3.Cutting of chorda increases salivary secretion after 1-2 weeks called paralytic secretion of saliva. 4.Pavlov established that conditioning forms the basis of learning by studying salivary reflexes.

*Q. DESCRIBE THE PROCESS OF DEGLUTITION: Def:-Deglutition or swallowing is a reflex process in which the food bolus passes from mouth through the pharynx and oesophagus into the stomach brought about by coordinated actions of muscles of tongue, pharynx, larynx and oesophagus. It occurs in 3 stages : 1.First stage or Oral stage:-In this stage, the food bolus prepared by mastication is squeezed backwards and downwards into the pharynx by the upward and backward pressure of tongue against palate. It is due to contraction of intrinsic muscles of tongue and is under voluntary control . 2.Second or Pharyngeal Stage:-In this stage, food bolus passes through the pharynx into the oesophagus. A)Movements which propel the food through the Pharynx:a)There is approximation of palatopharyngeal folds forming a midline slit through which the bolus passes. Here, large size objects are held back. b)Contact of bolus with pharyngeal deglutition receptors initiates contraction of sup. Pharyngeal constrictor producing a ring of constriction which moves downwards through middle and inf. pharyngeal constrictors propelling the bolus. This is called Pharyngeal peristaltic wave. C)As this wave reaches upper end of oesophagus, there is receptive relaxation of upper oesophageal sphincter (Cricopharyngeus) allowing the food bolus to enter the oesophagus. B)Movements which protect respiratory passage:a)Entry of food into the nasopharynx is prevented by contraction of tensor palate and levator palate. Soft palate becomes elevated, stiff and presses against post pharyngeal wall, shutting off the nasopharynx. b)Entry of food into larynx and lower resp. tract is prevented by i)stoppage of respiration (deglutition apnea) which results from inhibitor impulses coming from deglutition centre to respiratory centre. ii) approximation of true and false vocal cords closing the laryngeal opening iii) Hyoid bone and larynx are pulled upwards and forwards by contraction of neck muscles so that larynx moves out of the way of bolus. iv)Epiglottis swing backwards, becomes horizontal and covers laryngeal opening. Therefore food bolus passes along either sides of epiglottis towards oesophageal opening. 3.Third or Oesophageal Stage:- The pharyngeal peristaltic wave continues into the oesophagus as Primary oesophageal peristaltic wave and pushes the food bolus down the oesophagus (4 cm/s). In erect position, gravity accelerates movement of bolus. If food gets stuck up in the oesophagus, the local distension stimulates myenteric plexus and a constriction ring appears behind the bolus which travels downwards pushing the bolus. This wave is called secondary peristaltic wave when food bolus reaches lower end of oesophagus, there is receptive relaxation of lower oesophageal (cardiac) sphincter permitting the entry of bolus into the stomach. Neural control of Deglutition:First stage is voluntary and controlled by higher centres second and third stages are reflex and controlled by Deglutition Centre situated near Tractus solitarius at the junction of Pons and medulla. Second stage is initiated by stimulation of swallowing receptors and afferent impulses pass through trigeminal and glossopharyngeal nerves to this centre which then brings about sequential activation of pharyngeal and laryngeal muscles. In the third stage, afferents as well as efferents pass through the vagus. Suggestions: facebook.com/asifpatel.ggmc

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82 Applied Physiology:-Difficulty in swallowing (dysphagia) can occur in various conditions like a)inflammation e.g. pharyngitis, diphtheria, b)paralysis of muscles e.g. polio, myasthenia c) immobilization of larynx e.g. tuberculosis, cancer d)Oesophageal varices. *Q. DISCUSS THE REGULATION OF GASTRIC SECRETION. Gastric secretion occurs in 4 phases and is controlled by neural as well as hormonal mechanism. 1.CEPHALIC PHASE:-is the gastric secretion that occurs before the food enters the stomach. It is a preparatory phase and accounts for 20% of gastric secretion. It occurs in response to A)Presence of Food in mouth which stimulates tactile receptors and taste buds in mouth. Afferent impulses are carried to dorsal motor nucleus of vagus which controls gastric secretion. This centre sends efferent impulses through the vagus to the intrinsic plexus and gastric glands producing gastric secretion. This is an unconditioned reflex. B)Sight Smell or Thought of food:-Here, the impulses originate from visual centre, smell centre or appetite of hypothalamus and end on vagal centre stimulating it, which then brings about gastric secretion (appetite juice). It is a conditioned reflex. Cephalic secretion is increased in emotions like anger and frustration hypoglycemia and stimulation of lateral hypothalamus. 2.GASTRIC PHASE:Results from presence of food in stomach. It accounts for 2/3 rds of total gastric secretion. It can occur via Neural or chemical mechanism A) Neural reflexes:- i)Food in stomach stimulates stretch receptors which in turn lead to Vagovagal reflex or long reflex producing gastric secretion ii)stimulation of stretch receptors also leads to activation of local Meissners plexus which, in turn, stimulates gastric glands producing secretion (Intramural or shortreflex). B) Hormonal Mechanism :-Operates through the hormone Gastrin It is released from G cells of pyloric glands in response to 1)distension of stomach by food which leads to a vagovagal reflex, the efferent vagal fibers terminating on G cells and release gastrin releasing peptide. Distension of stomach can also bring about gastrin release by intramural reflexes. 2)Presence of secretagogues in stomach like alcohol, caffeine, Peptones and amino acids which directly act on G cells. Released gastrin then enters the blood, reaches the gastric glands and stimulates them to produce gastric secretion rich in HCL. However excess secretion HCL is prevented by 1)inhibitory effect of acidic chyme (pH less than by 7) on gastrin secretion. 2. Somatostatin . In this phase, neural mechanism is week but lasts longer. 3. INTESTINAL PHASE:-Occurs due to presence to chyme in small intestine. It results from release of the hormone gastrin (enteric gastrin)from G cells in duodenum and proximal jejunum in response to distension (via intramural reflex) or presence of secretagogues, especially, amino acids. It reaches gastric glands passing through blood and stimulates them. Another hormone called enteroxyntin is also released by chyme which stimulates gastric secretion. However, chyme in the intestine also brings about release of hormones like CCK, secretion and G.I.P. which have inhibitory effect on gastric secretion and thus provide a negative feedback mechanism controlling gastric secretion. 4. INTERDIGESTIVE PHASE:-Is the gastric secretion occurring in fasting state. It is small in quantity, poor in acid and rich in mucus mediated by neural as well as hormonal mechanism. Applied Physiology:-1.Vagotomy helps in controlling acid secretion in peptic ulcer. 2.Excess secretion of gastrin (Gastrinoma) is associated with hyper acidity and peptic ulcer (Zollinger Ellis syndrome) Suggestions: facebook.com/asifpatel.ggmc

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*Q. DESCRIBE THE MECHANISM OF FORMATION OF HCL IN STOMACH: The stomach secretes about 1500 ml of gastric secretion in 24 hours containing HCL, pepsinogen, mucus, intrinsic factor, enzymes and inorganic substances. SECRETION OF HCL:-HCL is secreted by parietal (oxyntic)cells of gastric glands. These cells are oval in shape and situated in superficial parts of gastric glands. They have an extensively branching system of small canals in their cytoplasm called Intracellular canaliculi. At one end, they open into the lumen of stomach and at the other end they extend deep into cytoplasm. The HCL is formed in these canaliculi and secreted into the lumen of the stomach.

Davenports mechanism for formation of HCL:-

1. In the first step, chloride ions are actively transported from the cytoplasm of parietal cells into the canaliculi by the activity of chloride pump. 2. As a result of transport of negatively charged chloride ions, the lumen of canaliculi becomes negative (-40 to -70 mv). Therefore positively charged K+ ions are attracted from the parietal cell cytoplasm into the lumen of the canaliculi. This process is a passive diffusion. 3. In the cytoplasm of parietal cells H2O ionizes to form H+ and OH ions. 4. The H+ ions are actively secreted into the lumen of canaliculi and in exchange, k+ ions are reabsorbed from the canaliculi into the cytoplasm. This process is brought about by a protein called Hydrogen Potassium ATPase (H+K+ pump) present in walls of the canaliculi. 5. The H+ and Cl ions present in canaliculi exert osmotic pressure, Therefore, water is driven by osmosis into the canaliculi forming HCL solution. 6. In the cytoplasm, CO2 that is produced by cellular metabolism (or by diffusion from blood) combines with water in presence of carbonic anhydrase to from carbonic acid (H2CO3) which then split into H+ ions and HCO3 ions 7. H+ ions combine with OH ions and in step 3 above to form H2O. 8. The HCO3 ions diffuse from the parietal cells into the blood and react with NaCl to form NaHCO3 in blood. (NaCl + HCO3 ---------> NaHCO3 + Cl). The chloride ions that are set free then diffuse into the parietal cell cytoplasm and are again actively transported into the canaliculi as in step and the process continues. The outward transport of HCO3 ions is coupled with inward movement of chloride ions. Thus the end result of this process is secretion of H+ and CI ions into the canaliculi and reabsorption of one HCO3 ions into the canaliculi and reabsorption of one HCO3 ion into the blood When HCL is secreted in large quantities, e.g. after meals, the HCO3 conc. in blood also increase . This is called post prandial alkaline tide. Pure uncontaminated HCl secreted by parietal cells has a conc. of 155-meq/l and pH of 0.8 Stimuli for HCl secretion:-1.Acetyl choline released from vagal nerve endings combines with M3 muscarinic receptors and increases intracellular Ca+. 2.Histamine binds with H2 receptors and activates adenylcyclase. 3.Gastrin increases intracellular Ca+ conc. and stimulates parietal cells. Applied Physiology:- HCl secretion can be suppressed 1) by drugs that block carbonic anhydrase (acetazolamide) 2) by drugs that block H2 receptors (cemetidine) 3)by drugs that block H+ K+ pump (omeprazole) and 4)by vagotomy. *Q. DESCRIBE THE MOVEMENTS OF STOMACH. HOW IS EMPTYING OF STOMACH REGULATED? The motor functions of stomach are 1. It acts as reservoir of food upto a capacity of 1.5 lit. 2. Mixing of food with gastric secretion. 3.Regulated release of chyme into the duodenum. Two types of movements are seen in stomach:Suggestions: facebook.com/asifpatel.ggmc

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84 1.Receptive relaxation :-When food enters the stomach, the resting tone of gastric smooth muscle disappears and stomach relaxes. This is called receptive relaxation. It is especially seen in funds and upper body of stomach. It results from vagovagal reflex initiated by distension of stomach. The vagal efferent endings release VIP which relaxes the smooth muscle. Functions:-1.It increases capacity of stomach by stretching out its walls and facilitates storage function. 2.Prevents rise in intragastric pressure. 2.Mixing or Peristaltic contractions:- These are the constriction rings passing along the stomach wall to pyloric end. They are initiated in the middle of body of stomach and have a frequency of 3/min. The contractions increase in force and velocity as they reach pyloric end. These contractions are controlled by Basic Electrical Rhythm (BER)of stomach (Gastric slow waves)which has same frequency(3/min).Functions:1.Propulsion:-a small amount of chyme is propelled into the duodenum with each contraction. 2.Mixing:- Antral peristaltic waves are very strong digging deep into the contents of stomach and facilitate mixing. Propulsion and retropulsion also facilitate mixing. Hunger contractions are similar to peristaltic contractions, but occur in fasting state. Another type of movement seen in fasting state is called Migrating Myoelectric Complex which is a powerful sweeping movement. Regulation of gastric Emptying:-is achieved by controlling the activity of antral peristalsis (pyloric pump) which facilitates emptying and the tone of pyloric sphincter which has opposite effects. Factors which promote gastric emptying are:1.Gastric Food volume (distension) increases activity of pyloric pump and relaxes pyloric sphincter by vagovagal reflex. 2.Gastrin has similar effects and facilitates emptying. 3.Liquid food is emptied faster because of less resistance at pyloric sphincter. 4.Emotions like anxiety, fear etc increase peristaltic activity. Factors which delay gastric emptying :-Duodenal factors have a negative feedback effect on gastric secretion as well as motility. Duodenal factors act via 2 mechanism: 1.Neural mechanism (Enterogastric reflex):Stimuli like distension of duodenum, irritation, excess acidic chyme, hyperosmolar fluid and protein breakdown products etc. Stimulate corresponding receptors in duodenal mucosa and afferent as well as efferent impulses pass through sympathetic, parasympathetic nerves and local myenteric plexus leading to inhibition of pyloric pump and increased tone of sphincter. Thus gastric emptying is controlled. 2.Hormonal mechanism:- A)Cholecystokinin:- excess fats in duodenal release CCK from I cells of duodenal mucosa. CCK causes competitive inhibition of gastric and increases tone of pyloric sphincter, thereby delaying the emptying of stomach. B)Secretin:-Entry of excess acid in duodenum releases secretin tone of pyoloric sphincter. C)Gastric Inhibitory Peptide:-released by K cells in response to fats and glucose in duodenum delays gastric emptying. Other factors like vagotomy, emotions like grief and solid foods delay gastric emptying. *Q. DESCRIBE THE REGULATION OF EXOCRINE SECRETION OF PANCREAS.

The exocrine portion of pancreas secretes about 1200-1500 ml of pancreatic juice in 24 hours. The secretion occurs in 3 phases and is controlled by neural as well as hormonal mechanisms. CEPHALIC PHASE:-is the secretion of pancreatic juice before food enters stomach. It occurs in response to 2 Stimuli: 1. Food in mouth (Unconditioned reflex) stimulates tactile receptors and taste buds in mouth and afferent impulses are carried to the

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vagal centre. 2) Sight, smell or thought of food (conditioned reflex) stimulates visual, smell or appetite centres which, in turn, stimulate vagal centre. The vagal centre then sends efferent impulses to the pancreas producing secretion. Vagal nerve endings release Ach which acts on acinar cells of pancreas and raises intracellular Ca+ conc. in them. The resulting secretion is small in amount, rich in enzymes and chloride ions and poor in water and bicarbonate. Vagal impulses to G cells also brings about release of gastrin which stimulates secretion. 2.GASTRIC PHASE:- is the pancreatic secretion in response to food in stomach. It occurs by 2 mechanisms. A) Neural reflex :-food in stomach stimulates stretch receptors. Afferent impulses pass through vagus to vagal centre which then sends efferent impulses to pancreas also through vagus causing enzyme rich secretion (gastropancreatic vagovagal reflex). B)Hormonal mechanism:- Distension of stomach or presence of secretagogues causes release of gastrin from G cells of pyloric gland by vagovagal or local reflexes. It reaches pancreas through circulation and stimulates acinar cells to produce enzyme rich secretion. 3.INTESTINAL PHASE:Entry of chyme into the intestine stimulates pancreatic secretion. It is the most important phase of pancreatic secretion and is mainly brought about by 2 hormones (A)Secretin: It is a polypeptide hormone (27aa) released by S cells of mucosa of duodenum and jejunum in response to acidic chyme(pH less than 4.5). It is released into the blood, reaches pancreas through circulation and acts mainly on cells of pancreatic ducts. In this cells it activates adenyl cyclase leading to formation of cyclic AMP. As result, the cells produce large quantity of watery pancreatic secretion rich in bicarbonates and poor in enzyme contents (Hydrolytic secretion). This secretion helps in neutralizing the acids end provides optimum pH for action of pancreatic enzyme. B) Cholecystokinin-Pancreozymin (CCK-PZ)- Is a polypeptide hormone (33 aa) produced by I cells of duodenal and jejunal mucosa in response to long chain fatty acids, peptones, amino acids, Ca+ ions etc. It reaches pancreatic acinar cells through circulation, increases intracellular intracellular Ca+ conc. and stimulates them to produce thick viscid juice rich in enzyme and poor in bicarbonate content. (Ecbolic secretion). The enzyme rich juice helps in digestion of fats and proteins. Secretin and CCK potentiates each other's effect on pancreas. Other Factors controlling pancreatic secretion 1. Sympathetic stimulation has inhibitory effect on pancreatic secretion by reducing blood flow. 2. Somatostatin: Inhibits acinar as well as duct cells. 3. Insulin stimutates enzyme secretion. *Q. DESCRIBE THE MOVEMENT OF SMALL INTESTINE:

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Small intestine shows following types of movement. 1.Segmentation contraction. 2. Peristalsis. 3.Migrating Myoelectric complex. 4.Movements of villi.

1.Segmentation(Mixing) contractions: Description: In this type, constriction rings appear at regular intervals along a portion of intestine dividing it into a number of segments. These rings are 1 cm in width and are due to contraction of circular muscle fibers induced by presence of chyme in the intestine. After GGMC MUMBAI

86 few seconds these rings disappear due to relaxation, but a new set of constriction rings appears in the midportion of previous segments, so that new segment are formed by joining together of adjacent halves of previous segments. After few seconds another set of constriction rings appears and the process continues. Frequency of these contraction is a 11-12/min in duodenum, 10 to 11/min in jejunum and 8-9/min in ilium. Types:1. Concentric: Where circular muscles all along the circumference contract. 2.Eccentric-Fibers contact along part of circumference. 3.Regular: Where the segments are spaced regularly. 4.Irrigular. 5. Pendular movements where long(up to 20 cm) segments are formed. Origin: These contraction results from basic electrical Rhythm (BER) of small intestine which has same frequency. Distention of intestine by chyme causes superimposition of bursts of action potential on peak of BER leading to contraction of circular muscles. Function: They mix the chyme with intestinal secretion and help in digestion. 2.By moving the chyme to and fro, they increase its exposure to intestinal mucosa and facilitate absorption. 3. They move slowly in analward direction and help in propulsion. 4. They increase blood flow to intestine. 2.PERISTALSIS : Description: Distention of intestine caused by chyme causes appearance of a deep constriction right (due to contraction circular fiber) on the oral side of distention and relaxation of smooth muscles fiber for a few cm on aboral side such a composite wave the travels in aboral direction successively through circular fibers and is called Peristaltic Wave. It travels at a speed of 0.5 to 2 cm/sec, being faster in proximal intestine. It travels for less than 10 cms and dies out another wave is initiated at this point and chyme is pushed further. Variants – 1)Peristaltic rush are strong and fast peristaltic waves arising from irritation of intestine . Antiperistalsis: are abnormal peristaltic waves travelling in oral direction Origin:- Peristaltic wave results from Myenteric reflex .i.e. stretching of intestinal wall stimulates local myenteric plexus leading to contraction of circular muscle fibers on the oral side. It travels in aboral direction because of polarity or gradient of intestine factors affecting . Peristalsis :- 1.Stimulation of vagus increases while stimulation of sympathetic fibers decreases peristaltic activity. 2. Emotions like anxiety increases peristalsis. 3. Gastroileal reflex increases ileal peristalsis. 4. CCK, dopamine, serotonin etc stimulate peristalsis. Functions:-1. Propulsion of chyme in analwards direction. 2. They also spread the chyme along intestine and facilitate absorption. Normal pattern: Normally, the peristaltic contraction are superimposed on segmentation contraction . 3. Migrating myoelectric complex: Are the sweeping peristaltic contractions seen in fasting state. They occur at intervals of 62 – 90 min, begin in stomach and pass all the way to ileocaecal junction sweeping the excess digestive secretion into the colon. 4. Movements of villi: a) side to side or lashing movements which facilitate absorption and mixing. B) Pumping or milking movement in which villus alternately shortens and elongates these movements empty central lacteals into the lymphatics. These movements are due to contraction of smooth muscle fibers in villi. Applied Physiology :- Intestinal movement disappear following abdominal surgery, peritonitis or hypokalemia- paralytic ileus. *Q. ENUMERATE GASTROINTESTINAL HORMONES, DESCRIBE PHYSIOLOGICAL ACTIONS OF ANY TWO OF THEM :Gastrointestinal hormones are the hormone secreted by the endocrinal cells (APUD cells ) of gastrointestinal mucosa. They are released into the blood and through the circulation reach their target organs in GIT. They include 1.Gastrin 2.Choleckystokinin pancreozymin. 3.Secretin 4.Enteroglucagon 5.Gastric inhibitory peptide (GIP) 6. Vasoactive Intestinal Peptide (VIP) 7.Somatostatin 8.Motilin 9.Bombesin 10.Glicentin 11.Serotonin 12.Substance p 13.Neurotensin 14.Entero-Oxyntin 15.Bulbogastrone. Suggestions: facebook.com/asifpatel.ggmc

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GASTRIN : Chemistry :- It is a polypeptide hormone containing 17 aa called G17 or little gastrin. Other forms like G34 (big gastrin with 34 aa) and G 14 (minigastrin with 14 aa) are also found. G 17 is abundant and physiologically active form. Site of Secretion :-1. G cells of pyloric glands 2.Intestinal G cells in duodenum 3.Islets of pancreas in fetal life. 4.In central nervous system - hypothalamus Stimuli for secretion:1.Distension of stomach or duodenum cause by bulk of food leads to vagovagal reflex, efferent vagal fibers terminating or G cells. 2.Presence of secretogogues in stomach like caffeine, alcohol, peptones and amino acids which act directly on G cells. 3. Stimulation of vagus. 4. Ca+ rich food. Physiological actions:-1. Mainly stimulates the parietal cells of gastric glands to produce HCl. 2.It also stimulates peptic cells to produce pepsinogen. 3.It stimulates gastric peristalsis and pyloric pump and promotes relaxation of pyloric sphincter. It therefore promotes gastric emptying. 4. Stimulates pancreatic acinar cells to produce enzyme rich pancreatic secretion. 5.Stimulates movements of colon. 6. Promotes growth of gastric mucosa (trophic effect). 7.Causes contraction of cardiac sphincter and prevents acid regurgitation into oesophagus. 8.stimulates secretion of bile and succus entericus. 9.Promotes relaxation of ileocaecal sphincter. 10. Stimulates secretion of insulin, glucagon and calcitonin. Control of gastrin secretion:- 1.Excess acidity of contents in pyloric antrum (pH less than 2) inhibits G cell. 2. Hormones like somatostatin, GIP, VIP and glucagon all have inhibitory effect on gastrin secretion. Applied Physiology: Excess secretion of gastrin by tumor called gastrinoma causes hyperacidity and peptic ulcer (Zollinger Ellis on Syndrome). Cholecystokinin - Pancreozmin (CCK-PZ):Chemistry :-It is a polypeptide hormone contaning 33 amuno acids (CCK-33). Other forms like CCK 39, CCK 58 etc are also found. Site secretion:- 1. I cells of mucosa of jejunum and duodenum. 2.Hypothalamus. 3.Peripheral nerves. 4. Cerebral cortex. Stimuli for secretion:- 1. Presence of excess fats in upper small intestine especially long chain fatty acids containing more than 10 carbon atoms. 2. Presence of protein digestion products like peptones and amino acids. 3. Ca+ rich food. Physiological actions:- 1. It stimulates pancreatic acinar cells by increasing intracellular calcium, leading to pancreatic secretion rich in enzymes. The resulting secretion helps in digeston of proteins and fats. 2. It causes contraction of smooth muscle of gall bladder and relaxation of sphincter of Oddi. It thus promotes expulsion of bile into the intestine and facilitates digestion and absorption of fats. This action is mediated via cyclic AMP. 3. It has inhibitory affect on gastric secretion by competitive inhibition of gastrin. 4. It decreases the activity of Suggestions: facebook.com/asifpatel.ggmc

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88 pyloric pump and causes contraction of pyloric sphincter. It, therefore, delays gastric emptying allowing more time for fat digestion in intestine. 5. It potentiates actions of secretin on pancrease. 6. Promotes growth of pancreas(trophic action). 7. Stimulates secretion of enterokinase. 8. Stimulates intestinal secretion. 9. Increases motility of small intestine and colon. 10. Stimulates secretion of glucagon. 11. Causes inhibition of feeding centre in hypothalamus and limits food intake. FUNCTIONS OF SALIVA:

1. Mechanical functions:- a) It helps in the process of mastication and formation of soft food bolus. b) Mucin in saliva act as lubiricant and facilitates swallowing. c) It keeps mouth moist and helps in speech. d) It protects buccal mucosa by diluting hot and irritant substances. 2. Antibacterial functions :- a) Continuous flow of saliva flushes the food remnants from mouth and prevents growth of bacteria. b) Enzymes like lysozymes, peroxidase and ions like thiocynates can kill the bacteria. c) Immunoglobulins present in saliva of IgA type, can destroy specific bacteria. Antibacterial functions of saliva maintain oral hygiene and prevents dental caries. 3. Digestive functions :- Saliva contains ptyalin which is an alpha amylase. It acts on boiled starch to form maltose. It acts at optimum pH of 7. 4. Gustatory function:- Saliva acts as solvent for taste substances and enables them to stimulate taste buds. 5. Excretory functions:- Saliva excretes urea, ions like thiocyanates, iodides, heavy metals like lead, bismuth and mercury, drugs like penicillin, and viruses like mumps and rabies virus. 6. Buffering function :- Saliva contains buffers like mucin, bicarbonate and phosphate buffers which maintain pH of saliva between 6 and 7, and prevent decalcification of teeth. These buffers also neutralise bacterial acids or gastric acid that regurgitates into the oesophagus. 7. Role in water balance. In conditions of dehydration, salivary secretion is reduced, there is dryness of mouth and stimulation of thirst centre leading to water intake.8) Temperature regulation: In some lower animals, rise in body temperature stimulates salivary secretion so that heat is lost in evaporation of saliva. *Q. PAVLOV'S POUCH: It is one of the methods to study gastric secretion in dogs. It was devised by a Russian Physiologist, Ivan Petrovich Pavlov. Preparation:-The dog is anaesthetized and abdomen opened. An incision is taken along the stomach wall parallel to greater curvature avoiding damage to blood vessels and nerves. A pouch is then made from the body of stomach in such a way that, the lumen of pouch is separated from the body of stomach by double layer of mucus membrane and the other open end of pouch is sutured onto the ventral aspect of dogs abdomen(gastric fistula). The nerve supply and blood supply of the pouch is kept intact. Uses and advantage:-1. Whenever main body of stomach secretes, the pouch also secretes gastric juice which can be collected through gastric fistula and studied. Since the nerve supply as well as blood supply of pouch is intact, it can be useful in studying neural as well as hormonal mechanisms causing gastric secretion(that is cephalic, gastric as well as intestinal phases). 2.The juice collected through the pouch is pure and uncontaminated because food passes through main body of stomach. 3.The quantity of juice secreted by the pouch always forms some constant fraction of the total gastric secretion. It is thus useful in quantitative study of gastric secretion also. Suggestions: facebook.com/asifpatel.ggmc

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Heidenhain's pouch is a similar preparation in dogs but it is denervated. Hence it is useful only to study hormonal mechanism to gastric secretion. Sham feeding is another technique to study cephalic phase of gastric secretion in dogs.

*Q. VOMITING:Def:-Vomiting is a reflex process of evacuation of contents of upper gastrointestinal tract through the mouth. Associated symptoms: Pallor, Nausea, Sweating, excess salivation. Stimuli for vomiting:- 1.Irritation of gastric mucosa(gastritis). 2.Irritation and distention of first part of duodenum. 3.Appendictis. 4.Intestinal obstruction. 5.Distension of bile duct, ureter. 6.Impulses arising from organs like heart, vestibular apparatus. 7.Impulses arising from special senses like ghastly sights, nauseating smells etc. Vomiting Centre:- All these afferent impulses are carried to vomiting centre situated in medulla near Tractus solitarius close to salivary centre, which then brings about vomiting. Events taking place during Vomiting:-

1. There is deep inspiration. 2. Hyoid bone and larynx are pulled upwards and forwards stretching the oesophageal opening. 3. There is stoppage of respiration and closure of glottis. 4. Soft palate becomes stiff and elevated shutting off nasopharynx. 5. There is relaxation of stomach, cardiac sphincter and oesophagus. 6. There is strong contraction of diaphragm and abdominal muscle causing increase in abdominal pressure which has a squeezing effect on stomach. This assisted by antiperistaltic waves forgoing the contents of stomach through the mouth to the exterior. Vomiting can also occur in response to stimulation of Chemoreceptor Trigger Zone (CTZ) situated in floor of 4th ventricle by drugs like morphine, apomorphine or by

metabolic products like urea and ketone bodies. Applied:- Prolonged vomiting can lead to loss of body water (dehydration) and alkalosis.

FUNCTIONS OF BILE:Bile is a green colored fluid secreted by hepatocytes. Its major functional component is the bile salts. (Na+ and K+ glycocholates and taurocholates). 1. Digestive functions:- Bile salts help in fat digestion in 2 ways : a) They reduce surface tension of large fat globules breaking them into smaller particles so that a larger surface area is available for action of lipolytic enzymes. this is called Detergent action or Emulsifying action. b) Bile salts also activate pancreatic lipase, which splits neutral fats into fatty acids and monoglycerides. 2)Absorptive function: Bile salts are essential for absorption of fats and fat soluble vitamins like A,D,E and K. Bile salts combine with fatty acids, monoglycerides and cholesterol in the human of intestine to form water soluble complexes called Micelles. These are spherical or cylindrical in shape,25 to 40 Angstroms in diameter and made up of 20-40 molecules of bile salts. The bile salt molecules are arranged in such a way that their water soluble polar groups are on the outer surface and fat soluble hydrophobic group in the interior containing the fatty substance. Thus fatty substances are made soluble in water(hydrotropic action) which is essential for their transport and absorption in the intestine. Bile also facilitates absorption of minerals like iron and calcium. 3)Excretory function of bile: excretes bile pigments cholesterol, lecithin, heavy metals like copper and zinc, drugs and bacterial toxins. Suggestions: facebook.com/asifpatel.ggmc

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90 4. Choleric Action: - Bile salts secreted in bile are reabsorbed and through enter hepatic circulation reach liver cells and stimulate them to produce more bile. 5. Neutralization: - Liver bile is alkaline and helps to neutralize gastric acid entering the intestine and also to maintain optimum pH for intestinal enzymes. 6. Bile salts keep the cholesterol in solution and prevent formation of gall stones. 8. Mucin in bile (from gall bladder) acts as lubricant and buffer.9. Bile has mild antibacterial action. Applied Aspects :- Bile is essential for life, obstruction of common bile duct results in failure of fat absorption and steatorrhoea.

Q. REGULATION OF GALL BLADDER EMPTYING :Normally, in the fasting state, sphincter of Oddi remains closed and bile accumulates in gall bladder. After meals certain stimuli arise which cause contraction of smooth muscle of gall bladder and relaxation of sphincter of Oddi causing expulsion of bills into the duodenum. These are 1. Neural mechanisms : stimuli like presence of food in mouth and stomach (unconditioned reflexes) or sight, smell or through of food (Conditioned) activate vagal centre which then sends efferent impulses to gall bladder causing contraction of bladder and relaxation of sphincter. On the other hand, sympathetic stimulation inhibits emptying of gall bladder. 2. Hormonal mechanisms :- Presence of excess fats and protein digestion products causes release of CCK from duodenal mucosa. It reaches gall bladder through circulation causing strong contraction of gall bladder and relaxation of sphincter leading to expulsion of bile. This is called cholegogue action. Gastrin also promotes emptying of gall bladder while VIP I inhibits emptying. 3. Effect of Peristalsis: Presence of chyme in duodenum increase its peristaltic activity. Since each peristaltic wave is proceeded by a wave of relaxation, there is momentary relaxation of sphincter of Oddi when peristaltic wave passes over it. thus a small quantity of bile is squirted into the duodenum with each peristaltic wave. 4. Other factors: - Drugs like adrenaline, histamine cause contraction of gall bladder while those like morphine, atropine etc. Inhibit it. Function of Gall Bladder:1. Storage of bile : Gall bladder is concerned with storage of bile. Storage is, essential because secretion of bile by liver is a continuous process while its expulsion into the intestine is an intermittent process. 2. Intermittent expulsion of bile: Gall bladder contracts in response to various stimuli like sight, smell, through of food, presence of food in mouth and stomach and the hormone CCK and thus release bile into the duodenum facilitating digestion and absorption of fats. 3. Concentration of Bile : Gall bladder absorbs water from bile and concentrates it about 10 times. The concentration function facilitates storage of large quantity of bile even through the capacity of gall bladder is small (35 to 35ml) Concentration of bile salts also facilitates micelle formation. 4. It helps in equalization of pressure in biliary tree. By absorbing water, it prevents excess rise of pressure in bile duct system and products hepatocytes. 5. It absorbs Na+, Cl- And HCO3- from absorption occurs electro genially. Because of absorption of bicarbonates, gall bladder bile is neutral while hepatic bile alkaline. 6. Gall bladder mucosa secretes mucus which is the source of mucin in bile which acts as buffer and lubricant. 7. It also excretes some cholesterol in bile SUCCUS ENTERICUS:I, the fluid secreted by intestinal glands. These are simple tubular glands (Crypts of lieberkuhn) present in intestinal mucus. About 1.5 to 2 litres of fluid is secreted in 24 hours. Composition :- Sp. gravity 1.010, ph- 7.6 to 8.0 Suggestions: facebook.com/asifpatel.ggmc

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Water : 98.5% Solids : 1.5% which include organic substances like enzymes (enterokinase), mucin and albumin and inorganic substances like Na+, Cl- And HCO3-. The concentration of inorganic substances is same is in plasma. Stimuli for secretion: 1. Presence of chyme in the intestine activates stretch receptors as well as contact receptors leading to stimulation of local Meissen’s plexus which activates intestinal glands to produce secretion. 2. Stimulation of parasympathetic fibers increases while sympathetic stimulation decreases the secretion 3. Hormones like secretin, CCK, VIP etc. Which are released in response to excess acid or fatty substances in the intestine also increase intestinal secretion. Functions:- 1. Enterokinase activities trypsinogen to trypsin.2 Protective function : Mucus protects surface epithelium from irritant material. Alkaline mucus secreted by Brunner’s glands protects duodenal mucus from gastric acid. 3. Water present in succus entericus acts as solvent for food particles and vehicle for transport of food towards epithelial cells. 4. Absorptive Function: succus entericus facilitates absorption by forming unstirred water layer.5. Digestive functions. Intestinal enzymes are present in brush border of epithelial cells. They include peptidases (Which covert peptides to amino acids, sucrase (sucrose to glucose and fructose), maltase (maltose to glucose), lactase (lactose to glucose and galactose) and intestinal lipases. Applied aspects: Cholera toxin causes strong stimulating of intestinal glands and excess intestinal secretion producing rice water stools.

SECRETIN :Is one of the gastrointestinal hormones. It was the first hormone discovered in 1902 by Bayle’s and starling. Chemistry :- It is a polypeptide containing 27 amino acids with structure similar to Glucagon, GIP and VIP. Site of Secretion : 1. Secreted by the 's' cells it is present in the form of a prohormone called prosecretin. 2. Neurons in limbic system. Stimuli for Secretion :- 1) Entry of acidic chyme into duodenum and jejunum. Its secretion starts when pH of chyme falls below 4.5 and secretion is maximum at ph.3 2) partially digested proteins and fatty acids also promote release of secretin. 3) Parasympathetic stimulation also has similar effect. Physiological actions : - 1. Secretin stimulates the duct cells of pancreas and causes secretion of watery pancreatic juice rich in bicarbonates. This action is medicated via formation of cAMP in, the S cells. The resulting alkaline secretion helps in neutralizing acid and also provides alkaline ph for action of intestinal enzymes. 2. It also acts on cells of bile ducts and stimulates secretion of bile rich in bicarbonates. Hydrocholeretic action :- 3. It potentiates effects of CCK on pancreas in causing enzyme rich secretion. 4. It has inhibitory effect on gastric acid secretion by inhibiting release of gastrin from calls and by inhibiting parental cell response to gastrin. 5. It decreases gastric motility and causes contraction of pyloric sphincter. It therefore delays gastric emptying. 6. It stimulates secretion of succus entericus 7. It stimulates chief cells of stomach to produce pepsinogen. 8. It stimulates insulin secretion by beta cells of pancreas. DEFECTION REFLEX: It is the reflex process of evacuation of contents of distal colon and rectum to the exterior. It is initiated by distension of rectum with fecal matter. Mass movements occurring in distal part of colon force the fecal components matter into the rectum. There are 2 components of defecation reflex. 1. Intrinsic defecation reflex of colon :- Distension of rectum stimulates stretch receptors and hence local myenteric plexus. Impulses spread into descending and sigmoid colon causing peristaltic waves which propel the fecal material towards anal canal. At the same time there is receptive relaxation of internal anal spinchter. If external spinchter is relaxed can occur. However, this intrinsic reflex is a weak reflex. 2. Parasympathetic defecation reflex :- Distension of rectum causes afferent impulses to pass through pelvic nerves to S2, S3, S4 segments of spinal cord (spinal defecation centre) which then send efferent impulses also Suggestions: facebook.com/asifpatel.ggmc

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92 through pelvic nerves to a) smooth muscle of descending and sigmoid colon producing strong peristaltic waves that sweep the fecal matter through the rectum to the anal canal. b) Internal anal sphincter causing its relaxation. At the same time, if circumstances are favorable for defection, certain voluntary activities are performed by a person to facilitate expulsion of faeces. These are assumption of proper posture, straining, voluntary relaxation of external anal sphincter (supplied by pudental nerves) and contraction of levator ani which helps in evagination of feces. Defecation reflex can be conditioned. Applied physiology :- A weak defecation reflex leads to constipation. Damage to spinal defecation centre can lead to incontinence of faeces. CONGENTAL MEGACOLON:- (Hirschsprung’s Disease). Also called Aganglionic megacolon, it is a condition seen infants and children. Audiology: It is due to congenital defect in my enteric plexus in a segment of colon, especially, sigmoid colon. Ganglion cells are absent in this segment and substance P content of the segment is low. Because of defective myenteric plexus, peristaltic movements cannot pass across this Aganglionic segment, Therefore fecal material accumulates in healthy part of colon proximal to this segment and prolonged accumulation of feces leads to dilatation of healthy portion of colon sometimes up to 3 to 4 inches in diameter. Hence this condition is called Mega colon. The defective segment itself remains small and contracted. Rectum remains empty. Defection reflexes are weak. Clinical features: There is severe constipation, the child passes stools once in a week or sometimes once in 3 week. There is loss of appetite, food intake is reduced and the child becomes externally emaciated. Dilation of colon lead to distension of abdomen and abdominal discomfort. Diagnosis can be established by: 1. Barium enema which will show the mega colon above the spastic segment and 2 by biopsy of defective segment of colon which will lack the myenteric plexus Treatment : The condition is treated by resection of aganglionic segment followed by resuturing of healthy segment proximal and distal to it.

Balanced Diet: Def: Balanced diet is a diet containing proper proportions of different components like proteins, carbohydrates, fats, vitamins,minerals and water, so that the individual maintains caloric balance, growth and positive nitrogen balance and does not develop any sign of deficiency or excess. Caloric requirements:- In a balanced diet should be equal to caloric expenditure of an individual which is 25003000 Calories for moderate worker, 2000-2500 C for sedentary worker and 3500 C for heavy worker. Additional calories should be provide for growth. Protein content should be 1 gm/kg body weight. Additional proteins should be given in pregnant and lactating mothers and growing children. Dietary proteins should include animal proteins like meat, fish, eggs, (of high biological value) which contain all essential amino acids. Proteins are essential for formation of new tissues, tissue repair, synthesis of enzymes, hormones, plasma, proteins etc. Fats: Fat contents of the diet should be 70-80 gs per day and they should contain essential fatty acids. They should provide 25% of caloric requirements of the person. (Caloric value 9.3 cal). Besides acting as source of energy, dietary fats provide fat soluble vitamins, essential fatty acids and increase palatability of food. Carbohydrates :- Carbohydrate content of the diet should be 450-500 gms per day. Carbohydrates (starch sugar, cereals etc.) in the diet act as major source of calories (60-65% of caloric requirement) thereby sparing breakdown of proteins and fats (portion and fat sparing function). They also form bulk of the diet. Vitamins: Balanced diet should contain proper amounts of water soluble vitamins like B complex and C and fat soluble vitamins like A, D, E, and K which perform specific functions. Suggestions: facebook.com/asifpatel.ggmc

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Minerals: Diet should also contain trace quaintest minerals like iron, copper, cobalt, manganese etc. They act as components of cellular enzymes. Water content of diet should be equal to water lasso’s son that water balance is maintained. In addition, diet should also contain leafy vegetables (cellulose) to prevent. Proteins form an important constituent of the diet. Sources of proteins in the diet are 1: Animal proteins like meat, milk, fish and eggs. These animal proteins contain essential amino acids and they are maximally utilized by the body, hence called First Class proteins (proteins of high biological value). 2. Plant proteins like cereals, pulses, groundouts or soyabean. They lack one or more essential amino acids. (Second class proteins). Proteins in diet have following functions :- 1. They are essential for formation for new tissues during growth, pregnancy, lactation etc. This is called tissue building function of proteins. 2. Replenishment of lost tissue (Tissue repair function) after tissue damage. 3. They are essential for synthesis of enzymes. 4. For synthesis of hormones. 5. For synthesis of plasma proteins. 6. Proteins can also act as source of energy, but in a balanced diet, they provide only 10% of caloric requirement. Requirement of proteins : - Normal healthy adult requires 1 gm proteins /kg/body wt/ day. Requirement is more (1.5 to 2 gm/kg) in convalescent patients. Specific Dynamic Action of Proteins:- When proteins are metabolized in the body, more heat is liberated than that which can be accounted for by caloric value reactions during transamination and deamination. Therefore more calories should be provided to compensate for SDA. Deficiency of proteins leads to a condition called Kwashiorkor in children characterized by failure of growth, dry lusterless skin, loss of hair, delayed milestones and hypoproteinemic edema.

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SPECIAL SENSES

Chapter 7

*Q. DESCRIBE THE COMMON ERRORS OF REFRACTION. HOW ARE THEY CORRECTED? In normal eye (emmetropia), parallel rays of light coming from distant objects are sharply focused on retina without using accommodation. (Far point at infinity), while the divergent rays from near objects can be focused by using accommodation (Near point at 10 to 25 cm). ERRORS OF REFRACTION : 1. MYOPIA (Short sightedness) : Parallel rays coming from distant objects are focused in front of retina, even with ciliary muscle fully relaxed. Therefore subject cannot see distant objects and far point is at a distance less than 6 meters. Near vision is not affected because convergent rays can be focused on retina: In fact, near point comes closure to the eye. Causes :- 1. Increase in antero-posterior diameter (elongation) of eyeball (axial myopia ) 2. Increased curvature of cornea or lens (curvature myopia) 3. Increased refractive index of lens (index myopia). Clinically, there are 2 types of myopia a) Simple myopia b)Progressive myopia. Correction: By using biconcave spherical lens which will diverge the parallel rays and bring them to focus on retina. 2. HYPERMETROPIA :- (Far sightedness): Here, parallel rays of light are focused behind the retina with accommodation relaxed. The subject can see distant objects by using accommodation. (Far point at infinity). But the divergent rays coming from near objects cannot be focused even with full accommodation. Therefore near objects have to be taken farther away from the eye to be seen, i.e. near point recedes from eye. Causes:1. Decrease in A.P. diameter of eyeball (axial hypermetropia). 2. Decreased curvature of cornea or lens 3. Removal of lens after cataract. Childhood type of hypermetropia disappears as age advances. Correction :- By using biconvex spherical lens in front of eye which converge parallel rays and focuses them on retina. 3. Presbyopia :- Is a condition seen after 40 years of age in which the subject cannot see the near objects distinctly. Cause :- It results from 1. gradual loss of elasticity of lens and its capsule 2. Weakness of ciliary muscle as age advance. Therefore accommodation power of the eye is reduced (from normal) 14 diopters to as less as 2 diopters and hence divergent rays from near objects cannot be focused. Near point recedes from eye. Presbyopic symptoms appear earlier in hypermetropes and at a later age in myopes. Distant vision is not affected, but if the lens becomes totally rigid, the eye remains permanently focused at a constant spot. Correction: - It is corrected by using convex lens for near vision (reading glasses) . If lens is rigid, then bifocal lenses are advised for near as well as distant vision.

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4. Astigmatism: Astigmatism is a refractive error of the eye that causes the visual image in one plane to focus at a different distance from that of the plane at right angles. Because the curvature of the astigmatic lens along one plane is less than the curvature along the other plane, light rays striking the peripheral portions of the lens in one plane are not bent nearly as much as the rays striking the peripheral portions of the other plane. If the subject is shown radiating lines. (Stigmatic chart), he fails to see all the lines simultaneously. Correction : By using Cylindrical lens oriented in proper meridian. Irregular astigmatism (Keratoconus ) is corrected by contact lenses. 5. Spherical Aberration :- Results from greater refraction of rays passing through peripheral parts of lens than those passing through central part. Normally corrected by.1 iris covering peripheral part of lens. 2. Lesser curvature of cornea at periphery. 6. Chromatic Aberration :- Image formed on retina has colored fringe due to splitting of white light as it passes through the lens. Errors of refraction are detected by using. 1. Snellen’s charts for distant vision. 2. Jaeger’s charts for near vision. 3. Astigmatic charts. 4. Ophthalmoscope. 5. Retinoscopy. *Q. Describe The Changes Taking Face In Human eye During Accommodation For Near Vision:-

Def:- A reflex increase in refractive power of eye in order to focus the divergent rays coming from near objects is called accommodation. Changes:- 1. The basic change is increase in anterior curvature of lens. 2. Constriction of pupils.3. Convergence of eye balls. The 3 changes together are called near response. This reflex is a parasympathetic reflex. Normally, the lens capsule is elastic and lens substance is completely relaxed and the lens is kept in a flattened state by the tense suspensory ligaments which are attached peripherally to the choroid body. The ciliary muscle which is present at the insertion of these ligaments has 2 sets of fibers: 1. Meridional fibers which extend backwards from commercial junction to choroid and 2. Circular fibers arranged in the form of a ring. When the eye looks at a near object, there is reflex contraction of ciliary muscle. Contraction of meridional fibers pulls the ciliary ring forwards and inwards while contraction of circular fibers has sphincters like action. Both these effect reduce the tension on suspensor ligaments and the lens tends to become spherical in shape because of natural elasticity of its capsule. There is increase in anterior curvature of lens mainly because 1. Lens capsule is thin Suggestions: facebook.com/asifpatel.ggmc

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96 anteriorly, 2. Presence of vitreous humor on its post. aspect. Increase in ant. curvature of lens increases the refractive power of eye (lens) by as much as 12 to 14 diopters. Thus the divergent rays from near object can be focused on retina and the subject can see the near object.

Pathway of accommodation reflex: The initial part of the accommodation reflex is a voluntary process because the subject has to look voluntary at the near object. Blurred image on retina – Stimulation of Y type ganglion cells – optic nerve – optic chiasma –optic tract- primary and secondary visual cortex- Frontal Eye field (or middle temporal gyrus neurons) - Corticonuclear fibers - Edinger Westphal nucleus (parasympathetic) – occulomotor nerve- ciliary ganglion – short ciliary nerves- ciliary muscle (contraction ). Amplitude of accommodation is the difference in refractive power of eye in resting state and fully accommodation state. Normally it is 12-14 diameters and goes on decreasing as age advances. Range of accommodation: is the distance between far point and near point. Phakoscopy :- Is a procedure to study increase in anterior curvature of lens. If a lighted candle is held in front of eye, 3 images called Purkinje Sanoson images are seen. When the person looks at near object, image from ant. surface of lens becomes smaller and shifts towards corneal image, indicating ant. bulging of lens. Other Responses: -1. Constriction of Pupils: - also occurs with accommodation. It helps to eliminate spherical aberration and increase dept of focus. Faith way sake as above, but the effector muscle is constrictor papillae. 2 . Convergence of eyeballs: - results from simultaneous contraction of medial recite on both sides so that the image of the near object falls on corresponding points of two retina. Applied Physiology: - After the age of 40 years, the accommodation power of the eye is reduced due to loss of elasticity of lens or weakness of ciliary muscle. Hence near objects cannot be seen- a condition called Presbyopia. Comparative Physiology: - In bony fish, accommodation results from elongation of eyeball. *Q. Describe The Process of Excitation of Photoreceptors

Photoreceptors are the rods and cones situated in retina. Each rod is an elongated cell (40-60 microns ) with a diameter of 2 to 5 microns. It is divisible into 4 parts: 1. Outer segment- which contains discs formed by infolding of cell membrane. It also contains Na channels. 2. Inner segment: - Contains 7cell organelles like endoplasmic reticulum, mitochondria, centrioles, vesicles and Na+ pump in its walls. 3. Nucleus:- Synaptic body which makes synapse with bipolar cells and horizontal cells and releases neurotransmitter glutamine on these cells. Photochemistry :-

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The photolabile pigment present in rods is Rhodopsin and that in cones is iodopsin. These pigments are present as transmembrane proteins in the discs present in their outer segments. Rhodopsin (mol. wt. 41,000) is a combination of protein called Scotopsin and a pigment called 11 cis retinal. The folded shape of 11 cis retinal fits into the shape of scotopsin. Decomposition of Scotopsin :- Light falling on the eye reaches rods and cones passing through all the layers of retina. Absorption of light by rhodopsin (absorption maximum 505 mm) causes photoactivation of electrons in retinal portion leading to instantaneous change from 11 cis from to all trans form of retinal which is a straight molecule and starts splitting away from scotopsin. During the process of splitting, various intermediate compounds are formed like Rhodopsin – Bathorhodopsin (Prelumirhodopsin)- Lumirhodopsin - Metarhodopsin I – Metarhodopsin II - Scotopsin + All trans retinal. Suggestions: facebook.com/asifpatel.ggmc

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98 Excitation of Rods :- Normally, in the resting (dark) State, the Na+ leak channels present in the outer segment of rods are open and Na ions continuously diffuse in through these channels producing dark current. These channels are open by cyclic GMP molecules. At the same time, the Na pump present in inner segment pumps out Na+ ions. The resting membrane potential of rods is -40 mv and in this state, they continuously release the neurotransmitter on bipolar and horizontal cells. When light falls on the eye, rhodopsin decomposes, and of the intermediate compounds, namely, metarhodopsin II activates a G-protein present in membrane of rod discs cells. Transduction : This transduction then binds with GTP and activates the enzyme phosphodiesterase which breaks down cyclic GMP keeping the Na channels patent. Therefore Na channels close. In each step of this process, the events are amplified, that is one metarhodopsin II activates many molecules of transducer each of which activates many molecules of phosphodiesterase and so on. Thus closure of a large number of Na channels stops the dark current, but the Na pump continues to remove Na ions leading to increase in the negativity inside the rods to – 70 to 80 mv. (Receptor Potential). Thus excitation of rods causes their hyperpolarization and decrease the transmitter released by these cells. Some bipolar cells called depolarizing bipolar cells are normally inhibited by the neurotransmitter released by rods. When light falls on the eye, hyperpolarization of rods, reduces transmitter released by them, thus these bipolar cells are disinherited causing their excitation, others (hyperpolarizing type) are inhibited by light. *Q. Describe The Visual Pathway And The Effects of Lesion At Various Levels

Retina: - Optic pathway begins in retina. Photoreceptors are the rods and cones which are connected to bipolar cells which in turn, end on ganglion cells. In the retina, there is reciprocal representation of visual field, nasal half of retina perceives lower half of visual field etc. Optic Nerve :- Is formed by axons of ganglion cells. Optic Chiasma :- Is the crossing of optic nerves. Fibers coming from nasal half of retina cross to opposite side while temporal fibers continue on same side. Optic Tract :- Is formed by fibers coming from temporal half of retina on same side and nasal of retina on opposite side. Majority of optic tract fibers end in dorsal lateral Geniculate nucleus (latter geniculate body). Some fibers or collaterals end in 1. Pretectal Nucleus:- for pupillary light reflex and fixation of eyes on objects of importance. 2. Superior colliculus :- For visuospinal reflexes and simultaneous movement of two eyes. 3. Suprachiasmatic nucleus: for control of circadian rhythm. 4. Ventral lateral geniculate nucleus which forms Suggestions: facebook.com/asifpatel.ggmc GGMC MUMBAI

secondary visual pathway going to areas` 18 and 19. 5. Brainstem nuclei: - For control of eye and head movements. Lateral Geniculate Body (of thalamus):- Cells of LGB are arranged in 6 layers. Layers II, III, and V receive temporal fibers from same side retina and I, IV, VI nasal fibers from opposite retina. Functions of LGB:- 1. Acts as relay centre. 2. Acts as gate for controlling impulses going to cortex. 3. Fusion of image. 4. Depth perception. Optic Radiation (Geniculocalcarine tract) :- Fibers arising from LGB pass through the posterior limb of internal capsule and end in primary visual cortex. Primary Visual Cortex :- Situated in the walls of calcarine fissure on medial aspect of occipital lobe (Area 17 or striate cortex). Fibers coming from upper quardant of retina end in upper wall of sulcus, those from lower quadrants in lower wall. Macular region has a large representation extending onto occipital pole. Fibers coming from the two eyes are arranged in alternate layers extending vertically. (Ocular dominance columns). Functions:- Main function of primary, visual cortex is perception of contrasts and borders. It contains 3 types of cells; 1. Simple cells which respond to lines of specific origination passing through centre of receptive field 2. Complex cells – Orientation specific, position, non specific and 3. Hyper complex cells – Line of specific lengths, angles etc. Secondary Visual Cortex (visual association area) : - extends anterior superior and inferior to primary area. (Area 18 and 19). It receives fibers from primary area. Function :- 1. It gives meaning to visual impression .2. Perception of 3 dimensional form 3. Perception of color. 1. 2. 3. 4. 5. 6. 7. 8.

LESION IN EFFECT Retina (detachment) Scotoma (blind spot) optic nerve Total blindness (anopia) on same side. (neuritis, injury) Optic chiasma Central Bitemporal hemianopia. Part (pituitary tumor) Optic chiasma outer Binasal hemianopia Part (bil. int. carotid aneurysm) Optic tract (abscess or tumor) Contralateral homonymous hemianopia Direct light reflex lost. LGB, optic radiation Opposite homonymous hemianopia. Visual cortex upper wall Opposite homonymous inferior quadrantanopia Visual association area word blindness.

*Q. Describe The Mechanism of Color Vision : Color vision is the ability to perceive different color that is, different wavelengths of light (Normal visual spectrum 400 nm to 750 nm). Color vision is a function of cones and a property of photopic vision. There are 3 types of cones corresponding to 3 primary colors. 1. Red sensitive cones containing a pigment called Erythrolabe (types of iodopsin which is maximally sensitive to light of 575 nm wavelength) 2. Green sensitive cones containing chlorolabe (absorption max 535 nm) 3. Blue sensitive cones containing cyanolabe (Absorption max. 445 nm). Mechanism of Color Perception: 1. Young Helmholz Trichromatic theory :- According to this presently accepted theory the perception of color depends upon the ratio of percentage stimulation of 3. Different types of cones. For example, when a monochromatic orange light (570 nm) falls on eye, it will cause 99% (of maximum) stimulation of red sensitive cones, 42% stimulation of green cones and no stimulation of blue ones. Thus the ratio of percentage stimulation will be 99: 42: 0 for red, green and blue cones respectively. This pattern is interpreted as orange Suggestions: facebook.com/asifpatel.ggmc

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100 color by the brain. Similarly 83:83:0 (equal stimulation of red and green cones) is interpreted as yellow, 0:0:97 as blue and 31:67: 36 as green. Equal stimulation of all 3 types of cones causes perception of white. 2. Granit’s theory :- States that there are 2 types of cones and ganglion cells; Dominator type which are stimulated by all wavelengths in visual spectrum and modulator types which have narrow spectral sensitivity and are responsible for color perception. 3. Herring’s theory : According to this theory, one color is perceived when a pigment is being broken down and another color when it is being synthesized. 4. Polychromatic theory : - States that there are 7 types of cones corresponding to 7 color in visual spectrum. 5. Rectinex theory. Color analysis at different Levels :1. Retinal level :- The type of ganglion cells transmit information about color. There are 2 types of ganglion cells in retina; some stimulated by all types of cones, other are stimulated by one types of color cones (through depolarizing bipolar cells) and inhibited by another type of cones through hyperpolarizing bipolar cells, such cells are, called opponent color. For example, red Green cells are stimulated by red cones and inhibited by green cones. 2. Lateral Geniculate Body (LGB) level :- Cells of LGB (in layers III, IV, V and VI) also respond to opponent colors like ganglion cells. In auditor, some cells respond to one type of cone in the centre of their receptive filed and another type of cones in peripheral portion, e.g. red centre green surround cells. 3. Primary Visual Cortex :- Color perceiving cells are arranged in vertical cylindrical columns called color Blobs. They are stimulated by contrast colors. Some cells are double opponent color cells, that is they are stimulated by red cones in the centre of receptive field and inhibited by red cones in surround: inhibited by green cones in centre and stimulated by green cones in the surround. Final region for color processing is in the Visual association areas on ventral surface of occipital and temporal lobes. Applied Physiology :- Inability to perceive certain colors is called color blindness. It is due to lack of synthesis of color pigment resulting from defective gene on X chromosomes.

Q. COLOR BLINDNESS: Def:- It is the inability to perceive one or more colors (or inability to perceive certain wavelengths of light). Color vision is a function of cones. Red-Green Color Blindness. When a single group of color receptive cones is missing from the eye, the person is unable to distinguish some colors from others. For instance, one can see in Figure 50–9 that green, yellow, orange, and red colors, which are the colors between the wavelengths of 525 and 675 nanometers, are normally distinguished from one another by the red and green cones. If either of these two cones is missing, the person cannot use this mechanism for distinguishing these four colors; the person is especially unable to distinguish red from green and is therefore said to have red-green color blindness. A person with loss of red cones is called a protanope; the overall visual spectrum is noticeably shortened at the long wavelength end because of a lack of the red cones. A color-blind person who lacks green cones is called a deuteranope; this person has a perfectly normal visual spectral width because red cones are available to detect the long wavelength red color. Red-green color blindness is a genetic disorder that occurs almost exclusively in males. That is, genes in the female X chromosome code for the respective cones. Yet color blindness almost never occurs in females because at least one of the two X chromosomes almost always has a normal gene for each type of cone. Because the male has only one X chromosome, a missing gene can lead to color blindness. Because the X chromosome in the male is always inherited from the mother, never from the father, color blindness is passed from mother to son, and the mother is said to be a color blindness carrier; this is true in about 8 per cent of all women. Suggestions: facebook.com/asifpatel.ggmc

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*Q. Describe The Mechanism of Hearing : Sound transmission into inner ear and formation of Traveling wave:

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Sound waves falling on ear causes vibrations of tympanic membrane which are transmitted through the malleus, incus and stapes into the inner ear at ovalwindow. Impedance matching mechanism amplifies the pressure on oval window 22 Times to overcome inertia of fluid in inner ear. Inward movement of footplate of stapes creates of pressure wave in perilymph of scala vestibule which is transmitted through the vestibular member to Basilar membrane causing its depression. The elastic tension that is built up in depressed basilar membrane initiates a wave that travels along the basilar membrane towards helicotrema called Travelling wave. The basilar membrane constrains about 30,000 basilar fibers; those at the base of cochlea are short, thick, stiff and less loaded and therefore have high natural resonant frequency. Apical fibers are long thin and have low natural frequency. When the travelling wave reaches that portion of basilar membrane which has natural resonant frequency equal to the frequency of the sound, the basilar membrane vibrates maximally (amplitude) as short distance while low frequency waves travel all the way to helicotrema. Moreover, the travelling wave moves, faster along basal part of basilar membrane because of high co-efficient of elasticity and thus permits separation of high frequency sounds. Thus the basilar membrane acts as frequency analyzer. Stimulation of organ of Corti

Is situated on basilar membrane extending from its base to apex in a spiral Manner. It is made up of inner and outer rods of Corti enclosing tunnel of Corti, hair cells, supporting cells and tectorial membrane. The hair cells which are the receptors for hearing are arranged in 2 sets. 1. Inner hair cells – Single row, 3500 in number, flask shaped, 12 microns in diameter. Function – hearing. 2. Outer hair cells- 15000 in number, 3-4 rows, cylindrical, 8 microns in dia. The apical surface of these cells have sterocilia which pierce through reticular lamina and are embedded on the undersurface of gelatinous tectorial membrane. Suggestions: facebook.com/asifpatel.ggmc

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When the basilar membrane vibrates, the hair cells are stimulated. When it vibrates upwards, the reticular lamina and hair cells rock upwards and inwards, relative to tectorial membrane leading to bending of cilia away from modiolus. This opens cation channels in hair cells though which K+ ions diffuse in, causing depolarization. Similarly when the membrane vibrates downwards, the hair cells are hyperpolarized. The sensitivity of hair cells is increased by a total potential difference of -150 mv existing across its membrane (Endolymph +80 mv). These receptor potentials modify the action potentials initiated in the nerve ending arising from the bases of hair cells, and these action potentials travel along the auditory pathway to the auditory cortex where sound is perceived. Perception of pitch (frequency) of the sound occurs by 2 mechanism: 1. Place principle:- That is, the place on basilar membrane which shows maximum amplitude of vibration, there being a high spatial tonotopic organization in auditory pathway from basilar membrane to auditory cortex. 2. Volley (frequency) Principle: In case of low frequency sounds (less than 200 cps), the number of impulses in cochlear nerve has same frequency as that of sound. Perception of loudness by 3 Mechanisms. 1. Amplitude of vibration of basilar membrane 2. Recruitment of adjacent hair cells. 3. Stimulation of certain high threshold hair cells.

Q. Describe The Mechanism of Stimulation of Taste Buds And Pathway of Taste Sensation. Taste buds are the specialized structures containing receptors for taste sensation, that is the gustatory cell. There are about 10,000 taste buds in the young adults and their number goes on decreasing. They are situated in the walls of circumvallate, fungiform and filiform papillae of tongue and also in palate, tonsillar pillars, wall of pharynx and epiglottis. Structure:- Each taste bud is an oval structure measuring 50-70 microns in length and 30 microns in diameter. It is made up of about 40 to 50 modified epithelial cells of 2 types:- The Gustatory cells (hair cells) : are elongated spindle shaped micron ill arising from one end and projecting through the taste pore. These micron ill are 2-3 microns in length and contain receptors for taste substances. From the base of hair cells arise the nerve fibers which invigilate into the hair cells life span of each cells is 10-12 days and they are replaced by mitosis from adjacent cells. 2.Supporting of sustentacular cells which are transitional forms of epithelial cells. Excitation of taste receptors :- On entering the mouth, the taste substance gets dissolver in saliva, diffuses, through the taste substance pore and combines with specific receptor proteins on the microvilli. This combination opens Na channels in the membrane of hair cells causing inward diffusion of Na ions and decrease in resting intracellular negativity. This depolarization is the receptor potential of hair cells which generates action potentials in the nerve endings which are carried into the gustatory pathway leading to perception of taste. Each taste bud can be stimulated by two, three or even four primary tastes, but it is maximally responsive to one type of taste. Pathway of taste sentstion :1. From anterior 2/3 rds of tongue :- Taste sensation is carried through lingual nerve and then through chorda tympani into facial nerve. The cell bodies of first order neurons are situated in geniculate ganglion and their central processes enter Tractus solitarius. 2. From posterior 1/3rd of tongue: Impulses pass through glossopharyngeal nerve to the cell bodies situated in petrous ganglion which are the first order neurons. Their central process enter Tractus solitarius. 3. From base of tongue, epiglottis and pharynx: Impulses pass through vagus nerve into nodose ganglion cells whose central processes enter Tractus solitarius. Suggestions: facebook.com/asifpatel.ggmc

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All these central processes then end in nucleus of tractus solitarius, the cells of which form second order neuron. Most of their axons ascend on the same side through medial lemniscus while a few cross to the opposite side. As they ascend they give collaterals to salivatory nuclei which are responsible for reflex salivation in response to stimulation of taste buds. The axons of second order neurons ultimately end in parvocellular portion of ventral postero medial nucleus of thalamus. These cells form third order neurons and their axon pass through internal capsule to the lower tip of post central gyrus and operculo-insular cortex in the floor of lateral sulcus. These areas form the gustatory cortex where the perception of taste occurs. Applied Physiology :- Damage to sensory fibers going through VII, IX or X nerves can cause loss of taste sensation (ageusia) from corresponding area. Taste blindness is inability to perceive certain taste substances (like PTC).

Q. Describe The Excitation Olfactory Receptors And The Olfactory Pathway: Olfaction or smell is a chemical sensation which is not well developed in human beings (micrometric). The receptors for smell are the olfactory cells situated in olfactory membrane which is present in upper part of nasal cavity covering upper 1/3 rd of nasal septum and surface of superior turbinate. It has an area of 2.5 of 5 cm olfactory cells are bipolar nerve cells, cylindrical in shape and towards the surface they have a dilated portion called olfactory rod (peripheral process) from which about 8-10 cilia. (olfactory hair) arise and project into the layer of mucus covering the olfactory epithelium. These olfactory hair contain the receptors of smell substance called odorant Binding Proteins. From the basal surface of these cells, their axon arise and collectively from olfactory nerve. There are about 100 million such olfactory cells and each cell has a life span of 60 days. Besides olfactory cells, the olfactory membrane also contains supporting cells and Bowen’s glands that secrete mucus. Excitation of Olfactory cells:- For a substance to be perceived by smell, it should be volatile and soluble in water and lipids (ordori ferrous substance). It reaches olfactory epithelium by diffusion through eddy current or by sniffing and gets dissolved in mucus. It then combines with odorant binding protein on olfactory hair and the combination activates adenyl cyclase leading to formation of cyclic AMP which increase membrane permeability to Na ions. Therefore Na ions diffuse into the cells decreasing normal intracellular negativity (-55 mv). On the other hand some substances cause hyperpolarization (generator potential) of olfactory nerves to the olfactory discharge going through olfactory nerves to the olfactory areas of the brain leading to perception of smell. Olfactory Pathway:- First order neuron are the olfactory cells themselves. their axons (olfactory nerve) pass through cribriform plate of ethmoid bone, enter the cranial cavity and end in olfactory bulb. Here, they synapse with 2 types of cells, the mitral cells and the tufted cells forming complex structures called olfactory golmeruli. These glomeruli also contain granule cells and periglomerular cells. Axons of mitral and tufted cells (Second order neurons) pass backwards through olfactory tract which then divides into. 1. Medial olfactory stria ending in midline septal nuclei, olfactory tubercle and opposite olfactory bulb- This pathway is conceited with primitive responses to smell like licking of lips, salivation etc. 2. Intermediate olfactory stria ending in ant. perforated substance and diagonal band of broca.3. lateral olfactory stria ending in prepyriform cortex, uncus and corticomedial portion of amygdaloidal nuclei. These areas are primary olfactory areas. From these areas impulses pass into hippocampus and hypothalamus. This pathway is responsible for selection or rejection of food from previous smell experience and for emotional and behavioral responses to smell. The newer olfactory pathway passes to the dorsomedial nucleus of thalamus and then into orbitofrontal cortex where conscious analysis of odour takes place. Olfactory pathway also contains some efferent fibers which end on granule cells and control the entry of smell impulses. This is the central mechanism underlying olfactory adaptation.

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104 Short Notes *Q. Auditory Pathway: First order neuron is the spiral ganglion cells. Its peripheral process arises from base of hair cells in organ of Corti and the central process forms the cochlear nerve which enters the medulla and ends in dorsal and ventral cochlear nuclei. From here, the next order neurons arise and most of their fibers cross to opposite side through trapezoid body and end in superior olivary nucleus. Some fibers ascend on same side and end in sup olivary nucleus of same side. Axon of these cells pass through lateral lemniscus, some of them synapsing in nucleus of lat lemniscus, other continue without synapsing and ultimately end in inferior colliculus. Fibers arising from these cells end in medial geniculate nucleus of thalamus in which the last relay occurs and fibers pass through auditory radiation and terminate in primary auditory cortex situated in supratemporal place of superior temporal gyrus and adjacent insular cortex. Some Fibers from these areas pass into secondary auditory (association) areas which surround the primary area. Peculiarities of auditory pathway :-1. High degree of spatial organization of fibers from cochlea, to auditory cortex. There are tonotopic maps in cochlear nuclei, inferior colliculi, medial geniculate nucleus and auditory cortex. 2. Extensive crossing of fibers though trapezoid body, commissure of probst and collicular commisure. 3. Collaterals go to RAS (for arouse response to loud sound) and vermis of cerebellum (equilibrium) 4. There are corticofugal fibers in the pathway which end around bases of outer hair cells and modify their sensitivity. The neurons of sup. Olivary nuclei help in detecting direction of sound while cortical neurons perceive frequency, intensity and tonal patterns of sound. Primary Taste Sensation:Taste is a chemical sensation that plays important sole in acceptance or rejection o food. There are 4 primary taste sensations. 1. Sweet :- This taste is due to organic substance like sugars (glucose, sucrose, fructose etc.) alcohol, aldehydes, glycols, ketone and some salts of lead and beryllium. Sweet sensation is best appreciated near the tip of the tongue. 2. Sour :- This taste is due to acids like hydrochloric acid, citric acid, butyric acid etc. Sourness of a substance is proportional to hydrogen ion concentration. This taste is better perceived on the sides of the tongue. 3. Bitter :- Alkaloids like quinine, caffeine, nicotine, strychnine,, organic substances like bile salts and inorganic salts like MgSO4 produce this type of sensation. Bitter sensation is better appreciated at the back of tongue near circumvallate papillae. 4. Salty :- This taste is due to ignitable inorganic salts like sodium chloride, potassium chloride etc. And is best appreciated at the sides of the tongue. The threshold of taste receptors for various primary taste sensations is different. The threshold is least for bitter substances (maximum sensitivity) moderate for sour taste and relatively high for sweet and salty sensations. Taste buds are specialized structures containing the receptors (hair cells or gustatory cells) for taste. A taste bud can be stimulated by 2 or more taste substances but it is maximally sensitive to one type of primary taste. Inability to perceive a particular taste sensation is called Taste blindness and it is due to genetic lack of receptors for that taste substance. Clinically it is tested by using a bitter substance called phenylthiocarbamide. *Q. FUNCTION OF MIDDLE EAR: Middle ear is a cavity in petro us part of temporal bone containing 3 ossicales and 2. muscles. Its functions are: 1. Transmission of sound waves :- Sound falling on tympanic membrane causes it to vibrate and these vibrations are transmitted through the malleus, incus and stapes to the oval window and into the fluid of cochlea. Tympanic membrane is critically damped. Sound transmission is best for frequencies between 300 and 3500 cps. 2. Impedance matching :- Sound vibrations in air produce only weak vibrations in cochlear fluid. This is called impedance and is compensated by impedance matching mechanisms which amplify the pressure of sound waves 22 time on oval window. 1. The surface area of tympanic membrane is 55 sq. mm. While that of oval window is only 3.2 sq. mm. Thus the pressure gets amplified 17 times as it is concentrated over smaller area (hydraulic press action). 2. The leverage Suggestions: facebook.com/asifpatel.ggmc

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provided by the malleus and incus increase pressure by 1.3 times thus gigging a total amplification of 22 times. These mechanisms make up 50 to 75% of matching for frequencies between 300 to 3000. The efficiency of impendence matching mechanism improves hearing by 15-20 decibels. 3. Attenuation reflex (tympanic reflex) :When a loud sound suddenly falls on ears, there is reflex contraction of tensor tympani and stapedius muscles. Tensor tympani is attached to handle of malleus (supplied by trigeminal nerve) and when it contracts, tympanic membrane becomes tense and is pulled inwards. Stapedius muscle is attached to stapes (supplied by facial nerve) and when it contracts, stapes is pulled outwards from oval window. Thus the ossicular chain becomes rigid and the oval transmission of sound waves (especially below 2000 cps) is suppressed. Pathway: Cochlea – Cochlear nerve- cochlear nuclei- superior- olivery nucleus- trigeminal and facial nuclei – contraction of muscles. Function : 1. Protective : It protects the cochlea from very found sound. However it is has a latent period of 10-80 m. sec. in which damage can occur. 2. Masking: It masks low frequency sounds (noise) in the surrounding 3. It decreases sensitivity of hearing to persons own loud speech. 4. The Eustachian tube maintains the pressure on two sides of tympanic membrane.

*Q. Audiometry:Is a procedure carried out to detect qualitative (type of deafness) and quantitative loss (in decibels ) of hearing. It is performed in a sound proof room. To test air conduction of sound, ear phones are fitted over the ears and sounds of different frequencies (tones) are presented one by one. The intensity of the sound is gradually increased till the subject hears the sound. Then the procedure is repeated with other frequencies. If the loudness of a tone has to be increased by 10 decibels above normal before it can be heard, then there is conduction loss of 10 decibels below normal. To test bone conduction, electronic vibrator or oscillator is placed over mastoid process and similar procedure is performed. The readings obtained are plotted on a graph paper with frequency of sound on horizontal axis and hearing loss in decibels on vertical axis. The record is known as Audiogram. In conductive type of deafness which results from failure of ossicular conduction, the air conduction values will be less than bone conduction values especially for low frequency sounds. Such conductive deafness occurs in otitis media, wax in ext. ear, otosclerosis etc. In nerve (sensorineural) deafness, which is seen in labyrinthitis, streptomycin toxicity, tumors of cochlear nerve etc. both air conduction and bone conduction are less than normal especially for high frequency sounds. Endolymphatic (Endocochlear) Potential : Def:- It is the potential difference existing between the endolymph in scala media and perilymph in scala vestibuli or tympani. Normal Value: - It is a steady DC potential of 80 mv in the resting state of cochlea, endolymph being positive with respect to perilymph. Recording: - It is recorded by inserting one electrode in endolymph and the other is kept in perilymph or on surface of head. Origin: The positivity of endolymph is due to its high concentration of K ions. K ion conc. in endolymph is 145 me/lit. These K. ions are actively secreted by the cells of stria vascularis. Factors affecting E.P : Any condition that reduces the metabolic activity of stria vascularis can decrease endo. potential for example, hypoxia, asphyxia, anesthesia, cyanide poisoning etc. Similarly movements of basilar membrane also produce a change in endo potential. Importance :- It greatly increase the sensitivity of hair cells by creating a total potential difference of 150 mv across their membrane (-70 mv) intracellular +80 mv of endolymph). Endocochlear potential should not be confused with cochlear micro phonic which is produced by summations of electrical activity in hair cells of cochlea when the basilar membrane vibrates and is affected by hypoxia asphyxia or anesthetics. Doorway Reflexes :- When light is thrown in one eye. pupil of eye constricts. It is a parasympathetic reflex pathway – photoreceptors – optic nerve- optic chiasma- of same side – occulomotor nerve- ciliary ganglion – Suggestions: facebook.com/asifpatel.ggmc

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106 short cillary nerve – constrictor pupillae. Function :- It prevents entry of excess light when eye is exposed to bright light. 2. Indirect (consensual) light reflex :- When light is thrown in one eye, pupil on other eye constricts (Parasympathetic). Pathway :- Same as direct light reflex impulses cussing to the opposite side two places. 1. Optic charisma 2. Protectable nucleus to opposite Edinger Westphal nucleus. 3. Accommodation reflex:- There is constriction of pupils is when eyes look at near objects. This is also a parasympathetic reflex. Pathway :- Retina – optic nerve- optic chiasma – optic tract- LGB- primary and secondary visual cortex – Portal nucleus – occulomotor n- ciliary ganglion – Constrictor pupilae. Function :- Pupillary constriction cuts off peripheral divergent rays and helps to eliminate spherical aberration. It also increase of focus. 4. Cilospinal reflex:- Pinching of skin on the nape of neck (T) causes dilation of pupil. It is a sympathetic reflex. Pathway:- Skin – ciliospinal centre in spinal cord (T) sup cervical ganglion – Plexus around internal carotid artery- nasociliary nerve- long ciliary nerve- dilator puplillae. Applied aspects: - 1. Argyll Robertson pupil :- Lesion in pretectal nucleus, light reflex absent, accommodation reflex present. 2. Horner’s syndrome:- Damage to cervical sympatric fibers supplying dilator pupilage. Therefore puppies remain constricted.

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RENAL PHYSIOLOGY

Chapter 8

*Q. Describe The Structure of Glomerular Membrane And Mechanism of Glomerular Filtration. The process of urine formation involves 3 basic functions 1) Glomerular filtration. 2) Tubular reabsorption. 3) Tubular secretion. The malphigian corpuscles (glomerular capillaries + Bowmen’s capsule) act as ultra filters and filter all the constituents of plasma except colloids(includes plasma proteins). The membrane through which the filtration takes place is called Glomerular membrane: It is made up of 3 layers : 1. Capillary endothelial cell layer:- Made up of flat and fenestrated cells. These cells have pores with diameters of 70 to 100 mm. 2. Basement Membrane :- is a thin layer formed by network of collagen and proteoglycan filaments. It consists of 3 layers lamina rara interna, lamina densa and lamina rara externa. 3. Epithelial cells of visceral layer of Bowman’s capsule:These cells are known as Podocytes because they have numerous foot processes resting on basement membrane. These processes divide to form many finger like processes called pedicels which interdigitate and completely surround the capillaries. The gaps between adjacent pedicels are called filtration slits (sits pores) bridged by a thin diaphragm. The overall permeability of glomerular membrane is much more than capillaries elsewhere in the body and depend upon 1) effective size of pores :- These allow molecules having as diameter upto 8 mm to pass through while larger molecules are held back and (2) the negative charges (glycoprotein’s) lining the pores in all 3 layers of membrane repel the negative ions and oppose their filtration. Thus the glomerular filtrate formed is an ultrafiltrate of plasma which is essentially protein free (0.03%) . Mechanism of Filtration:- The process of filtration is a passive process and depends upon the balance of starling’s forces acting across the glomerular membrane. They are 1) Glomerular capillary hydrostatic pressure (HG):- Normal value 60 mm Hg. it is an outward driving force and favors filtration. 2) Colloid osmotic pressure of plasma (COP) : is an inward force and opposes filtration, normal value 32 (not 28 m as in other capillaries because as plasma is filtered, proteins are left behind causing a rise in colloid osmotic pressure) . 3. Hydrostatic Pressure in Bowman’s capsule (HB):- Normal value 18 mm Hg. It opposes filtration. 4) Colloid osmotic pressure of glomerular filtrate (COGF) : Is a force that promotes filtration of fluid but since filtrate is protein free its value is 0. Thus the total outward forces favoring the filtration are HG+COGF = 60+0= 60 mm Hg. Total inward forces opposing the filtration are COP+HB=32+18=50 mmHg. Therefore net filtration pressure = 60-50= 10 mm Hg. Thus a net filtration pressure (or effective filtration pressure of 10 mg Hg. is responsible for filtration of 125 ml of fluid in glomeruli per minute (Glomerular Filtration Rate). Hence the filtration co-efficient (K) is 125/10 =12.5 ml/min/mmHg. As more and more fluid is filtered along the length of glomerular capillaries its colloid osmotic pressure starts rising and a stage is reached at which net filtration stops. This is called filtration equilibrium. Besides the Starling’s forces, glomerular filtration also depends upon permeability of glomerular capillaries and their surface area. Suggestions: facebook.com/asifpatel.ggmc

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108 The effect of various factors on GFP can be expressed by an equation given below. GFR = K [(HG+COGF) - (COP+HB)]

*Q. Define G.F.R. Describe The Factors Affecting G.F.R.:Glomerular filtration rate is the quantity of glomerular filtrate formed in all the nephrons of both the kidneys per minute. Its normal value is 125 ml/min or 160 L/24 hrs. The process of filtration is a passive process and depends upon the balance of starling’s forces acting across the glomerular membrane. Factors affecting GFR are: 1. Autoregulation of GFR by Tubuloglomerular feedback mechanisms :- a) Afferent arteriolar vasodilator feedback mechanisms : Decrease in GFR – Decrease in filtered load of Na and Cl – macula Densa cells– afferent arteriolar vasodilatation- increased glomerular pressure and blood flow - increased GFR. b. Efferent art. Vasoconstrictor mechanism : Decrease in GFR – decreased Na and CI load – stimulation of macula densa – Juxtaglomerular cells – Renin –Formation of Angiotensin – Ang II- Constriction of efferent arteriole – Increase in glomerular pressure- increase in GFR. 2. Autoregulation by myogenic mechanism :- Increase in arterial pressure upto 160 mm Hg does not cause any significant change in GFR, because rise in arterial pressure causes distension of afferent arteriole and stretching of smooth muscles leading to constriction. This prevents any rise in glomerular capillary pressure and any change in GFR. 3. Effect of Renal blood Flow:- Increase in RBF increases GFR by 2 mechanisms; 1) by increasing glomerular capillary pressure which favors filtration and 2) by causing filtration to take place along greater length of glomerular capillaries by shifting the filtration equilibrium point more towards efferent arteriole. 4. Constriction of efferent arteriole :- Moderate constriction increases the resistance to the outflow and hence pressure in glomerular capillaries and GFR. But severe constriction causes stagnation of blood and rise of colloid osmotic pressure leading to fall in GFR. 6. Hydrostatic pressure in Bowmen’s capsule is normally 18 mmHg and opposes filtration. Conditions like obstruction of ureter by stone or tumor will increase this pressure leading to decrease in GFR. 7. Plasma Colloid Osmotic pressure: - Has a normal value of 32 mm Hg in glomerular capillaries and it opposes filtration. Increase in cor (dehydration) decreases GFR. On the other hand hypoproteinemia (liver disease, nutritional) increases GFR. 8. Permeability of glomerular membrane :- GFR is directly proportional to permeability. Permeability is changed in diseases like acute and chronic glomerulonephritis, nephrosclerosis etc. with corresponding changes in GFR. 9. Surface area of glomerular membrane :- GFR is directly proportional to surface area of glomerular membrane. It may he reduced in diseases of kidneys destroying glomerular partial or total nephrectomy. Angiotensin II causes contraction of mesengial cells leading to decrease in area of glomerular membrane and hence GFR. 10. Colloid Osmotic Pressure of glomerular filtrate: favors filtration but normally it is insignificant because glomerular filtrate is essentially protein free. The effects of above on GFR can be expressed by the equation. GFR = P x A [(HG+COGF) - (COP+HB)] Where P is permeability and A is area of glomerular membrane. *Q. Describe The Mechanism of Concentration of Urine in The Kidneys : Ability of kidneys to concentrate urine depends upon three factors: 1. Creation of hyperosmolarity in renal medullary interstitium and a gradient of osmolarity towards inner medulla by the counter current multiplier effect of loop of Henle. 2. Maintenance of hyperosmolarity and gradient of osmolarity by the countercurrent exchanger action of vasa recta Suggestions: facebook.com/asifpatel.ggmc

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. 3. Ability of ADH to increase water reabsorption from collecting duct which depends upon medullary hyperosmolarity. 1.Creation of hyperosmolarity in Medullary interstitium :Results from 4 mechanism: a) Active transport of Na k and C1 ions from thick ascending limb of loop of Henle. b) Active transport of Na ions from collecting duct. c) Passive diffusion of urea from collecting duct into medullary interstitium. Secondary to water reabsorption. d) Diffusion of Na ions from thin ascending limb of loop of Henle into the interstitium. Also there is gradient of osmolarity in renal medulla, osmolarity goes on increasing from renal cortex (300 mosmoles/lit) towards medulla and becomes 1200 to 1400 mosmoles/lit at the tip of renal papilla.

Countercurrent system is the one where inflow and outflow are close to each other, parallel to each other and opposite in direction. Such a situation exists in case of loops of Henle of Juxtamedullary nephrons. As the isotonic tubular fluid moves down the descending limb of loop of Henle, water diffuses out by osmosis and its electrolyte conc. goes on increasing towards inner medulla since this limb is impermeable to electrolytes. The thin ascending limb is permeable to Na ions, which therefore diffuse out into the interstitium along the conc. gradient. In the thick ascending limb, there is active transport of Na, K and Cl from tubular fluid into interstitium. Since water is not reabsorbed (this segment is impermeable to water), tubular fluid becomes hypotonic. As more and more ions are transported out of the ascending limb into the interstitium, it becomes more hypertonic and promotes further osmosis of water out of the descending limb leading to further concentration of electrolytes as the fluid moves towards tip of loop. These ions are further removed from ascending limb and the cycle continues. Thus this system has a multiplying effect on conc. Of electrolytes in tubular fluid, hence called countercurrent multiplier system. 2. Maintenance of Medullary hyperosmolarity and gradient of osmolarity :- Results from 2 mechanisms. a) Countercurrent exchanger function of vasa recta. Vasa recta are long straight loops of the capillaries extending upto tip of medulla in case of juxtamedullary nephrons. They are permeable to water as well as electrolytes. As the blood flows down the descending limb of vasa recta, it is exposed to higher conc. of electrolytes, so Na, Cl and urea diffuse into the blood while water diffuses out by osmosis. Thus as the blood moves up in ascending limb of vasa recta, electrolytes diffuse out and water diffuse in. Therefore by exchanging electrolytes and water, the two limbs of vasa recta ensure that solutes are retained in the medulla and not washed away. b) Sluggish blood flow in renal medulla also prevents wash out of solutes. 3. Action of ADH :- In presence of ADH, the cells of collecting duct become highly permeable to water, therefore water moves from collecting duct into hypertonic interstitium by osmosis and the process can continue till the urine becomes highly concentrated (up to 1200 mosmoles/lit). Suggestions: facebook.com/asifpatel.ggmc

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110 Importance:- This mechanism permits conservation of water in the body in conditions of dehydration and poor availability water.

Q. Describe The Process of Sodium Reabsorption In Renal Tubules. What Are The Factors Affecting It? About 99.3% of filtered Na is reabsorbed by the renal tubules and only 0.7% is excreted in urine. Na reabsorption in Proximal Convoluted Tubule:About 65% of filtered Na is reabsorbed in PCT. It is an active process and the renal oxygen consumption is proportional to rate of Na reabsorption. It occurs in two steps: 1) The epithelial cells of PCT contain Na-K pump on their basal and lateral surfaces. This protein pumps (actively) the Na ions into lateral and basal intercellular spaces and decreases conc. of Na ions in these cells. 2) The resting negativity of epithelial cells and the fall in Na conc. creates an electrochemical gradient for Na ions to move from tubular fluid into the epithelial cells (transcellular pathway) in combination with a carrier protein (Facilitated diffusion). This entry of Na occurs by 3 mechanisms. a) Uniport (symport) Mechanisms: in which Na is transported along with another substance like glucose or amino acid by the same carrier protein b) Antiport Mechanism : In which one hydrogen ion is secreted into the tubule in exchange for every Na ion absorbed (Na-H counter transport in acidosis) c) Chloride driven Na Transport : Absorption of Cl ions into the lateral intercellular spaces creates a negativity in these spaces causing diffusion of Na ions through the apical junctions. (paracellular Pathway). This occurs in distal half of PCT. The Na ions thus absorbed are again pumped into the lateral and basal spaces from where they enter peritubular capillaries. Na reabsorption in Loop of Henle: About 27% of filtered Na is reabsorbed here. There is no Na reabsorption from thin descending limb of loop which is impermeable to sodium. Some Na ions are absorbed by passive diffusion in the thin ascending limb (of juxtamedullary nephrons). In the thick ascending limb Na ions are actively absorbed with K and Cl ions, secondary to the activity of Na-K pump. Na reabsorption to Distal Tubule and collecting ducts: About 7% Na is reabsorbed in these parts. In early distal tubule, Na is absorbed along with Cl ions by Na-C1 symporter secondary to action of Na-K pump. In late distal tubules, Na reabsorption is a function of Principal cells. They contain Na-K pump in their basolateral membranes which creates electrochemical gradient for Na ions which then diffuse in through the membrane channels. Factors affecting Na reabsorption: 1. Starling’s forces acting across peritubular capillaries :- Fall in peritubular capillary hydrostatic pressure promotes Na and water reabsorption, while increase in pressure reduces it. As more Na ions accumulate in lateral spaces, they leak back into the lumen through apical junctions. Similarly decrease in colloid osmotic pressure promotes Na reabsorption and rise in it, opposes absorption. 2. G.F.R. :- Increases in GFR increase filtered load of Na and there is proportionate increase in quantity of Na reabsorbed. This is called Glomerulotubular balance. 3. Aldosterone: Aldosterone promotes Na reabsorption from distal tubules by increasing activity of Na pump. Its secretion depends on plasma K levels renin angiotensin activity, and dietary Na intake. 4. Cortisol: Deoxycorticosterone, progesterone and oestrogens also increases Na+ reabsorption. 5. Atrial Natriuretic Hormone:- Suppresses Na reabsorption from distal tubule and increase Na excretion. *Q. Describe The Process of Reabsorption of Water in Renal Tubules and Factors Affecting it: Normally about 180 liters of water is filtered in the glomeruli in 24 hours and of this 178.5 lit (more than 99% is reabsorbed by the renal tubules) and only 1.5L it is excreted in urine Suggestions: facebook.com/asifpatel.ggmc

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Water reabsorption in Proximal Convoluted Tubule : About 65 to 70% of filtered water is reabsorbed in PCT. Various solutes like Na, organic solutes, Cl, HCO3 etc. which are absorbed by the epithelial cells are transported into lateral intercellular spaces where they accumulate and increase the osmolality in these spaces. Therefore water diffuses by osmosis into these spaces. Entry of water occurs through the epithelial cells [transcellular pathway] and also through apical junctions [paracellular pathway] . As a result hydrostatic pressure in these spaces increase and water along with solutes enters peritubular capillaries. This process of water reabsorption is an iso-osmotic process and does take part in urine dilution or concentration, hence called obligatory water reabsorption. Fluid leaving the PCT is iso-osmotic. [300 mosmol/] . Loop of Henle: About 15-20%, water is reabsorbed here. This reabsorption occurs in thin descending limb of loop, which is freely permeable to water. As the tubular fluid flows down the descending limb, it is exposed to more and more hypertonic medullary interstitium and water diffuses out by osmosis. Therefore osmolality of tubular fluid increases up to 1200 mosmoles/lit. Water is not reabsorbed in thick ascending limb of loop of Henle which is impermeable to water, but solutes are actively transported out of the tubule, therefore tubular fluid leaving the loop is slightly hypotonic. Distal tubule: Early part of distal tubule is impermeable to water but absorbed solutes making tubular fluid more hypotonic [100 mosmoles/lit], hence called diluting segment collecting. Tubule and collecting duct: About 10-20% water reabsorption occurs in distal tubule and collecting ducts. It is under the control of anti-diuretic hormone. Thus water reabsorption helps concentrate or dilute the urine and is called facultative reabsorption. Under the influence of ADH, epithelial cells of collecting duct become highly permeable to water. Therefore water diffuses by osmosis from tubular lumen into the hypertonic medullary interstitium. This process of water reabsorption can continue till the osmolarity of tubular fluid rises to equal that of interstitium [up to 1200 mosmoles/lit] allowing excretion of highly concentrated urine. In the absence of ADH, water is not reabsorbed and hypotonic urine is excreted. FACTORS AFFECTING REABSORPTION OF WATER 1. Starlings forces acting across peritubular capillaries: Fall in capillary hydrostatic pressure, increase in colloid osmotic pressure of plasma, increase in hydrostatic pressure in lateral intercellular spaces etc. increases reabsorption of water. 2. Osmolarity of plasma: regulates water reabsorption through secretion of ADH. When osmolarity increase, ADH is secreted, water reabsorption increases[in excess of solutes] and osmolarity comes back to normal. 3. ADH: Increases water reabsorption from collecting tubules and collecting ducts. 4. GFR: Increases in GFR increases filtered load of water and there is proportionate increase in water reabsorption. This is called glomerulotubular balance. 5: Sympathetic stimulation increases proximal tubular water reabsorption. 6. Hormones: Aldosterone, angiotensin II, glucocorticoids increases Na reabsorption and secondary increase in water reabsorption. 7. Atrial natriuretic peptide: Decreases water reabsorption secondary to loss of Na+ ions. Applied physiology: Lack of ADH in diabetes insipidus causes decrease in water reabsorption and passing of large volume of urine. *Q. Describe in brief the process of urine formation. [Basic theory of nephron function]

Mechanism of urine formation involves three basic process. These are: 1.Glomerular filtration: In this process, about one fifth of the plasma that is following through the glomerular capillaries is filtered into the Bowman’s capsule. The malphigian corpuscles act as ultrafilters and filter all the components of plasma except proteins. Filtration takes places through a membrane called glomerular membrane consisting of endothelial cell layer basement membrane and podocyte cell layer. It permits passing of substances up to 6 to 8 nm diameter to pass through and resists passage of anions. The process of filtration Suggestions: facebook.com/asifpatel.ggmc

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112 is passive process and occurs due to presence of net filtration pressure of about 10 mm of Hg. About 125 ml of glomerular filtrate is formed in both kidneys per minute [ 180 liters /day] called glomerular filtration rate . GFR is autoregulated by Tubuloglomerular feedback and myogenic mechanisms and is changed mainly by change in renal blood flow under physiological conditions. 2. Tubular reabsorption: In this process, as the glomerular filtrate flows down the renal tubule, ‘wanted’ substances are reabsorption into peritubular capillaries and unwanted substances are allowed to be excreted. Reabsorbed substances include a. Sodium: About 99.3% of filtered Na+ is reabsorbed by renal tubule 65% in proximal tubules 27% in Loop of Henle and 7% is distal tubule. It is an active process and is regulated by aldosterone, GFR, natriuretic hormone etc. b. Water: About 178.5 lit of water [more than 99%] is reabsorbed by the tubules in 24 hours and only 1.5 lit is excreted. Reabsorption of water is passive, occurs by osmosis and is secondary to change in Na reabsorption. Distal tubular water reabsorption is under control of ADH of can be modified to excrete either dilute or concentrated urine [facultative reabsorption]. c. Potassium: About 92 to 95% of filtered K+ is reabsorbed by renal tubules, about 65% in PCT [by solvent drag mechanism] and remaining in thick ascending limb and early distal tubule by Na+ k+ cl- symporter protein secondary to the action of Na+ k pump. d. Glucose: All the filtered glucose is reabsorbed in PCT and no glucose is excreted in urine. The process involves secondary active transport where glucose is co-transported with Na+ by the same carrier protein. If filtered glucose exceeds transport maximum [ TmG = 375 mg /min], glucose appears in urine. e. Bicarbonates: are absorbed in PCT in the form of carbon dioxide. f. Amino acids: are totally reabsorbed in PCT by secondary active transport. g. Urine acid and urea: About 10% of filtered uric acid in absorbed in PCT while 60% of filtered urea is absorbed, some from PCT and some from collecting duct. 3.Tubular secretion: It is the process in which certain substances are secreted into renal tubules and are allowed to be excreted. Secretion of K+: About 80 to 100 meq. of k is secreted in 24 hours . It is secreted by the principle cells of distal tubule in which k is pumped into the cell from interstitial fluid by Na k pump and these K+ ions then diffuses into the lumen of tubule. The process is mainly controlled by aldosterone. Secretion of H+ ions: H ions are secreted by a. Cells of PCT by Na+-H+ counter-transport mechanism and b. By intercalated [brown] cells of distal tubule by the action of H pump. These H+ ions are formed by dissociation of H2CO3. Secretion of H+ ions is increased in acidosis. 3. Secretion of NH3: Ammonia formed by deamination of glutamine in cells of PCT diffuses into the lumen and combines with H+ ions to from NH4+ permitting more secretions of H+ ions. 4. Certain drugs are also secreted by renal tubules. *Q. ENUMERATE KIDNEY FUNCTION TESTS. DESCRIBE ANY TWO OF THEM. These are the tests carried out to assess the functions of kidneys and the degree of damage to the kidneys. Some of them are also useful for diagnosis of kidney disease. Various Renal Function tests are: 1. Urine examination. 2. Blood analysis: a) estimation of serum urea (normally 15-30 mg%) b)serum creatinine: (normally 0.6 to 1.5 mg%) c) estimation of Serum electrolytes (normally Na+ 142 meq/lit and K+ 4 to 5 meq/Iit) d) pH of blood Suggestions: facebook.com/asifpatel.ggmc

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3. Clearance Tests: a) Inulin clearance test for measurement of GFR. b)Urea clearance test- indicates ability of kidneys to excrete urea c) PAH clearance test measures renal plasma flow d) Creatinine clearance test (GFR) 4. Concentration and dilution test: 5. Other tests like X ray, KUB for stones, intravenous pyelography for visualization of urinary tract, Ultrasonography, CT scanning etc. 6. Renal biopsy. A) URINE EXAMINATION 1) Physical characteristics : a) Volume: normally 1 to 1.5 lit per day. Polyuria is seen in conditions like chronic Pyelonephritis, diabetes insipidus and mellitus. Oliguria is seen in acute glomerulonephritis, shock, dehydration etc. b) Specific gravity : normally between 1.01 to 1.025. Increased in proteinuria and glycosuria. Low sp. gravity in chronic renal diseases and diabetes insipidus. c) Color : normally straw coloured. Dark yellow in jaundice and red in hematuria due to tumor, trauma or calculus . d) pH: normally slightly acidic. More acidic in acidosis and less acidic in chronic renal diseases due to failure of secretion of H+ ions. 2) Chemical Examination a) Proteinuria: occurs when there is damage to glomerular membrane as in acute and chronic glomerulonephritis, nephrotic syndrome etc. b) Sugar: in diabetes mellitus c) Bile Salts and bile Pigments in jaundice d) Ketone Bodies in diabetic ketoacidosis e)Blood in urine in cases of bleeding from urinary tract 3) Microscopical examination:- a) Pus cells found in acute infections of kidney b)RBCs in conditions of hematuria c) Granular and hyaline casts in chronic renal diseases d) Crystals of oxalates and phosphates are found in cases of renal calculi. *Q. DESCRIBE THE PHYSIOLOGY OF RENAL CIRCULATION Functional Anatomy: Kidneys get their blood supply through renal arteries arising from abdominal aorta. Each renal artery enters the pelvis of kidney and divides to form segmental arteries which in turn divide to form interlobar arteries. These interlobar arteries then pass between the medullary pyramids towards renal cortex and divide to form arcuate arteries situated along corticomedullary junction. Arcuate arteries then give rise to interlobular arteries which proceed towards outer cortex and in their way give rise to afferent arteries which divide to form tuft of capillaries invaginating into Bowmans capsule. The glomerular capillaries reunite to form efferent arterioles which then divides into a second set of capillaries called peritubular capillaries which ultimately join to form interlobular veins. These interlobular veins reunite to form arcuate veins and then interlobar veins which ultimately join to form renal vein. 1) Normal renal blood flow is 1200-1300 ml/min (21 to 25% of cardiac output) which is very high on weight basis, but is essential for elimination of unwanted substances and urine formation. 2) There are 2 sets of capillaries in renal circulation (hence it is a portal circulation); a) Glomerular capillaries have high pressure(60 mm Hg) inside them because efferent arteriole is shorter and narrower than afferent arteriole. This high pressure facilitates filtration of fluid which is the main function of this capillary bed. B) Peritubular Capillaries are low pressure (13 mm Hg) capillaries. Moreover, they are in proximity with renal and distal tubules and therefore help in tubular absorption and secretion. They also supply oxygen and nutrients to and remove CO2 from cells of proximal and distal tubule. 3) In case of juxtamedullary nephrons long straight capillaries Called vasa recta arise from deeper parts of peritubular plexus. They have sluggish blood flow and they maintain medullary hyperosmolarity and gradient by CounterCurrent exchange mechanism. 4) There are shunts in renal circulation like Ludwigs shunt (afferent arteriole-peritubular capilaries),Trueta shunt (vasa rectavenous plexus). 5) Autoregulation: Renal blood flow and GFR remain fairly constant in case of changes in arterial pressure from 80 to 160 mm Hg. This autoregulation is due to 2 mechanisms: a) myogenic mechanism. Suggestions: facebook.com/asifpatel.ggmc

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114 b) Tubuloglomerular feedback mechanisms like i) afferent arteriolar vasodilator mechanism and ii) efferent arteriolar vasoconstriction mechanism. 6) Renal blood flow is affected by a) Sympathetic stimulation causes constriction of afferent decreasing Renal Blood flow and GFR b) Hormones: i) Epinephrine and norepinephrine have similar action ii) Angiotensin II in moderate quantities, causes constriction of efferent arterioles and increases GFR iii) Prostaglandins and kinins dilate renal vessels and increase in blood flow. c) exercise-renal blood flow increases during exercise 7) Decrease in renal blood flow and GFR causes activation of Renin Angiotensin mechanism for regulation of arterial pressure and ECF volume 8) Measurement of Renal blood flow can be done by two methods a) by using Fick principle b) by measuring renal plasma flow by PAH clearance test and using hematocrit value.

SHORT NOTES *Q. Glucose Transport Maximum (TmG) Defn : TmG is defined as the maximum amount of filtered glucose which can be reabsorbed (transported) by the renal tubules in one minute. Normal value- 375 mg/min. Mechanism of Glucose absorption :Normally all the filtered glucose is absorbed by epithelial cells of proximal convoluted tubule. The process occurs through secondary active transport in which Na+ pump, creates an electrochemical gradient for Na+ ions. Therefore ions in the lumen combine with a carrier protein which also has a site for glucose. Thus both Na+ and glucose are transported into the cells (symport or cotransport). Relation between filtered glucose & absorbed glucose: Normally 100-125 mg of glucose is filtered every minute into the tubules and, all this is absorbed in PCT. As blood increases filtered glucose increases and glucose reabsorption also increases till the filtered glucose reaches 375mg/min i.e TmG. All the filtered glucose above this value, is excreted in the urine. Causes of TmG: TmG is similar to Vmax of any carrier mediated transport 1) At this level of filtered glucose, all the carrier proteins are saturated 2) Limitation is also due to the time required for the carrier protein to undergo conformational change from one state to another and back. Renal threshold for glucose: Is the level of blood glucose at which Glucose starts appearing in urine. The actual value for renal threshold (180 mg%) is much lower than expected value (about 375 mg%). This is called splay and is due to the fact that TmG of all nephrons is not same, some have lower TmG value. TmG remains normal in diabetes mellitus. *Q. JUXTA GLOMERULAR APPARATUS: It is a complex structure situated close to the glomerulus consisting of following components : i) JG cells: These are the modified smooth muscle cells in tunica media of afferent and efferent arteriole. They are swollen, epithelial in appearance and contain a prominent nucleus, golgi apparatus and prorenin granules. ii) Macula Densa Cells : Are the cells of distal convoluted tubule situated in the angle between afferent and efferent arterioles. The cells appear dense under microscope with their golgi apparatus directed towards JG cells.

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iii) Mesenglial cells: These are star-shaped cells situated between glomerular capillary loops with their processes extending into the spaces between endothelial cells and basement membrane. iv) Extramesenglial cells: situated outside the glomerulus in the triangle formed between afferent and efferent arterioles and Distal tubule FUNCTIONS i) Release of Renin: The JG cells release renin in response to a) fall in arterial pressure b) decrease in renal blood flow and c) increased sympathetic discharge to kidneys. Renin then acts on Angiotensinogen to form Angiotensin which is then converted into Ang II by Angiotensin converting enzyme. Angiotensin II then increases blood pressure and blood volume by various actions: 1- Strong peripheral vasoconstriction. 2- Stimulates ADH secretion. 3Stimulates thirst centre. 4- Stimulates secretion of aldosterone 5- causes Na and water retention by direct action on kidneys. ii) Formation of erythropoietin: In response to hypoxia, the JG cells and Lacis Cells produce renal erythropoietic factor which converts erythropoietinogen to erythropoietin which then stimulates erythropoiesis and increases RBC count iii) Regulation of GFR: Macula Densa cells can detect the filtered load of Na and Cl- ions. This is called efferent arteriolar vasoconstrictor Mechanism which is a part of tubuloglomerular feedback in autoregulation of GFR. iv) Mesengial cells are also concerned with phagocytosis and deposition of intercellular matrix. In addition, they can cause kinking of glomerular capillaries in response to Ang II and thereby decrease their surface area and GFR.

Q. FUNCTIONS OF VASA RECTA

Vasa recta are long straight capillary loops arising from deeper parts of peritubular capillaries of Juxtamedullary nephrons. They have a descending limb and an ascending limb and extend deep into the medulla upto the tips of renal pyramids.

Functions:

i) Maintenance of hyperosmolarity of medullary interstitium by countercurrent exchanger function: As the blood flows through the

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116 descending limb of vasa recta it exposed to increasing osmolarity of medullary interstitium. Since it is freely permeable to water as well as solutes, solutes diffuse into it while water diffuses out by osmosis. Hence osmolarity of blood goes on increasing as it moves into deeper medulla and reaches upto 1200 mosm/lit. Then as the blood flows through ascending limb, it is exposed to decreasing osmolarity. Therefore the net result is that the solutes diffuse out of ascending limb and into the descending limb thereby preserving the solutes in medulla by recirculation. This is known as countercurrent exchanger function. Sluggish blood flow in vasa recta also prevents washout of solutes. ii) Maintenance of gradient of osmolarity in medulla: The anatomical arrangement of ascending and descending limbs of vasa recta and their free permeability helps to maintain the medullary gradient. If the gradient in the interstitium is reduced at any point, then solutes will diffuse out from vasa recta to re-establish the gradient. iii) Vasa recta also provides oxygen and nutrients to the medullary structures like cells of collecting ducts and remove CO2 and waste products. Q. INULIN CLEARANCE TEST: It is the test that measures the amount of plasma that is cleared off its inulin in one minute. It indicates Glomerular Filtration Rate. Properties of inulin: i) It is a polysaccharide found in tubers. ii) It is freely filtered in glomeruli. iii) Neither reabsorbed nor secreted by tubules. iv) Harmless to body. v) Doesn’t bind to proteins. vi) Not lost into tissues.vii) Easily measurable. Since inulin is freely filtered with the plasma, the amount of inulin filtered is proportionate to the amount of plasma that is filtered which is GFR. Principle of Inulin clearance : Amount of filtered inulin = GFR x Plasma inulin concentration(P) Amount of excreted inulin in one minute= Urine inulin conc/ml(U) x Volume of urine/min (V) Since inulin is neither reabsorbed, nor secreted, filtered inulin = excreted i.e. GFR x P= U x V i.e. Procedure: Initially a loading dose of inulin is given followed by sustained IV infusion to maintain plasma constant. Then urine sample collected for a period of 10 minutes and U and V are measured. A blood sample is collected and plasma inulin is measured. From this, the amount of plasma cleared of its inulin is calculated. Normal value of inulin clearance is 125 ml per minute.

*Q. MICTURITION. It is a reflex process of emptying of urinary bladder when it is filled. It is a spinal parasympathetic reflex but can be initiated or suppressed voluntarily. 1) Micturition reflex : As the bladder fills with urine (250 to 300 ml), the stretch receptors in bladder wall and bladder neck are stimulated. They send afferent impulses through the pelvic nerves to the spinal micturition centre situated in S2 and S3 segments of spinal cord. This centre then sends efferent impulses also through the pelvic parasympathetic nerves to the bladder causing contraction of detrusor muscle and relaxation of internal urethral sphincter. Contraction of detrusor muscles increases intravesical pressure (micturition waves in cystometrogram) which further stimulates, stretch receptors leading to stronger contraction. Thus it is a self regenerative reflex. When micturition reflex becomes strong enough efferent impulses pass through, pudental nerves causing relaxation of external urethral sphincter and urine is passed out through the urethra. Suggestions: facebook.com/asifpatel.ggmc

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Higher control of micturition: High centres in cerebral cortex (in motor cortex near the representation of perineal muscles) and in pons keep the spinal micturition centre partially inhibited and keep ext. sphincter in contracted state. Voluntary initiation of micturition results from i) Facilitation of micturition centre ii) relaxation of external sphincter . iii) rise in intra-abdominal pressure forces urine into bladder neck initiating micturition reflex. Applied aspects :- i. Damage to sensory nerves from bladder produces Atonic bladder which overflows drop by drop. Here micturition reflex is absent. ii. Automatic bladder occurs in damage to spinal cord above sacral region in which higher control is lost and bladder empties spontaneously by micturition when it becomes filled. *Q. CYSTOMETROGRAM

It is a graph showing intravesical pressure changes (on vertical axis) in response to change in volume (horizontal axis) of urine in the bladder. Cystometry is the procedure for recording this graph. Initially, catheter is inserted into the bladder and it is emptied completely. Then water is filled in the bladder in steps of 50 ml and bladder pressure is recorded at each step. A Cystometrogram shows following phases: i) When the bladder is completely empty, intravesical pressure is nearly zero. ii)With accumulation of first 30 to 50 ml Urine, intravesical pressure rises 5 to 10 cm of water. This is called phase Ia. iii) Further accumulation of 200 to 300 ml urine causes only a small rise in pressure(upto 15 ml of water). This is called phase Ib and is attributed to Laplace's law. Pressure in a spherical viscous P=2t/r i.e. with increase in urine accumulation tension as well as radius of bladder increases, therefore pressure almost remains constant. This is due to plasticity of detrusor muscle- stretching of detrusor muscle by rising volume of urine causes its relaxation, thus minimizing rise in pressure. iv) Beyond 300 to 400ml, further accumulation causes sudden and sharp rise in intravesical pressure (phase II). At this urine volume, micturition reflex is initiated causing appearance of micturition waves superimposed on pressure changes. These micturition waves are acute periodic increases in pressure lasting from few seconds to more than a minute, the pressure rising upto 80 to 100 cm of water. FUNCTIONS OF KIDNEY A) Excretion of end product metabolism specially end products of protein metabolism like urea (from amino acids), uric acid (from nucleic acids) and creatinine (muscle). It also excretes end products of hemoglobin, like urobilinogen and metabolites of hormones. Excretion results from non-reabsorption and secretion of these substances from renal tubules. B) Regulation of body fluid osmolality and volume: Working together with cardiovascular system, nervous system and hormones, kidneys regulate GFR and water reabsorption from tubules and therefore control ECF osmolality and volume. C) Regulation of Electrolyte balance: Kidneys regulate blood levels of various inorganic ions like Na+, K+, Ca+, Mg++, Cl-, H2CO3, PO4- and inorganic ions like citrate and succinate. Regulation is achieved by controlling absorption as well as secretion of these ions so that there is perfect matching between daily intake and secretion. Regulation of these ions is absolutely essential for cellular function. D) Maintenance of H+ conc. (pH) of body fluids: Kidneys regulate H+ ions conc. by controlling reabsorption of bicarbonates, by secretion of H+ ions and by formation of ammonia. E) Endocrine functions: a) Renin: released from JG cells in response to fall in arterial pressure helps in short term regulation(by Renin-angiotensin mechanism) as well as long term regulation of arterial pressure and blood volume by Renin-Aldosterone Mechanism. b) Erythropoietin: In hypoxic conditions, kidney cells produce Suggestions: facebook.com/asifpatel.ggmc

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118 renal erythropoietic factor leading to formation of erythropoietin which then stimulates erythropoiesis and increases RBC count to overcome hypoxia. c) 1,24 Dihydroxycholecalciferol : It is formed in cells of proximal tubules by action of 1-alpha hydroxylase and is essential for Ca absorption from GIT. d) Prostaglandins and kinins: regulate renal blood flow. F) Excretion of drugs and their toxic substances from body. G) Synthesis of new substances like ammonia, Hippuric acid, phosphates etc*Q. JUXTAMEDULLARY NEPHRONS Nephron is a structural and functional unit of kidney. Each kidney consists 1.2 million nephrons which are of 2 types: 1) Cortical nephrons and 2)Juxtamedullary nephrons Features of JM nephrons: a) The glomeruli of these nephrons are situated in deeper portions of renal cortex adjacent to medulla, hence called JM nephrons. b) They form about 15% - 20% of total nephrons. c) Their glomeruli are larger in size than cortical nephrons. d) Diameter of afferent and efferent arterioles is almost equal. e) Loop of Henle is long (upto 14 mm) and extends deep into the medulla upto the tips of renal pyramids. f) Ascending limb of loop of Henle has a thin segment at its beginning which is permeable to solutes. g) From deeper parts of peritubular capillaries arise long straight capillary loops called Vasa recta which also extend deep into medulla lying close to loops of Henle. They have a sluggish blood flow. Functions: 1) Long loops of Henle acts as countercurrent multiplier system and cause development of hyperosmolarity in medullary interstitium 2) Vasa recta, acts as countercurrent exchangers and preserves hyperosmolarity and gradient of osmolarity in medullary interstitium. Both these functions are essential for concentration of urine 3) JM nephrons are concerned the Na conservation in the body 4) Vasa recta provides nutrition to and remove waste products from collecting ducts.

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CENTRAL NERVOUS SYSTEM

Chapter 9

*Q. CLASSIFY SYNAPSES, DESCRIBE THE PROCESS OF SYNAPTIC TRANSMISSION. Defn: Synapse is a Junctional region between two neurons across which nerve signals are transmitted and modified. CLASSIFICATION A) Depending upon nature of transmission :1. Chemical synapse 2. Electrical Synapse 3. Conjoint synapse B) Anatomical classification 1) Axosomatic Synapse 2) Somatic synapse 3) Axoaxonic synapse C) Physiological classification 1) Excitatory synapses 2) Inhibitory synapses Structure of Synapse: The endings of presynaptic neurons form knoblike structures called synaptic terminals or presynaptic terminals. These terminals contain: 1) large number of vesicles containing the neurotransmitter (50 nm). 2) Mitochondria which provides energy and enzymes for synthesis of neurotransmitter 3) Voltage-gated calcium channels and 4) release Site proteins. There is a gap, 200-300 A° wide, between presynaptic knob and postsynaptic neuron called synaptic cleft, which is filled with ECF and proteoglycan filaments to which enzymes cholinoesterases are attached. The postsynaptic membrane contains the receptors for the neurotransmitter. Each receptor protein has two components: a) a binding component which binds to the neurotransmitter and b) an ionphore component which is a ligand-gated channel of Na+ or Cl- channel, or an enzyme that can form cyclic AMP or activate genes or protein kinase. Transmission: 1. Arrival of impulse at presynaptic terminal causes depolarization of its membrane. 2. This opens voltage-gated calcium channels through which Ca++ ions diffuse, from ECF into presynaptic terminals. 3. These Ca ions combine with release site proteins and cause fusion of synaptic vesicles with presynaptic membrane 4. Thus neurotransmitter is released by exocytosis into the synaptic cleft. Amount of neurotransmitter released is proportional to calcium influx. 5. The neurotransmitter (eg. acetyl choline) diffuses through the synaptic cleft and combines with receptors i.e. Ach-gated Na channels. 6. As a result, these Na+ channels open and Na+ ions diffuse into the postsynaptic membrane causing a decrease in intracellular negativity. 7. This decrease in negativity is called Excitatory Post Synaptic Potential(EPSP) which is a graded and transient (15 msec) potential change. 8. Summation of many such EPSPs can decrease the negativity to threshold value (-55 mv) leading to generation of action potential in initial segment(Axon Hillock) of postsynaptic neuron. 9. In case of inhibitory synapses, the neurotransmitter(Glycine, GABA) opens Cl channels in postsynaptic membrane causing further increase in negativity. This is called Inhibitory Post Synaptic Potential (IPSP). 10. After its action, transmitter is removed by a) diffusion into ECF b) destruction by enzymes like acetyl cholinesterase c) reuptake into neurons. Applied physiology: 1. Storage of memory occurs in the form of facilitated synaptic circuits (Pre-synaptic potentiation). 2. Drugs like anaesthetics depress synaptic transmission and produce anaesthesia. Suggestions: facebook.com/asifpatel.ggmc

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120 *Q. CLASSIFY RECEPTORS. DESCRIBE THE PROPERTIES OF RECEPTORS Def :- Receptor is a specialized structure which acts as biological transducer converting the changes in internal and external environment (stimuli)into nerve impulses. Classification: I. Depending upon the Nature of stimulus A)Mechanoreceptors (responding to mechanical Stimuli) : a) Cutaneous receptors like Meissner’s corpuscles, Merkel’s discs, hair end organs, free nerve endings, Pacinian corpuscles, Ruffini's endings etc b) Deep tissue receptors like muscle spindles, Golgi tendon organs. c) Baroreceptors in vascular tree d) Hair cells in cochlea, otolith organs and semicircular canals B)Thermoreceptors (responding to temperature): like warmth and cold receptors, Ruffinis organs, Krause bulb.(mainly free nerve endings). C)Nocicepters (for Pain) free nerve endings D)Chemoreceptors (for chemical substances) like central and peripheral chemoreceptors, smell receptors, taste receptors. E)Electromagnetic receptors (for Em waves) like rods and cones for light F)Osmorecepters (responds to osmotic changes) in hypothalamus, duodenum etc.

II. Depending upon situation of receptors: A) Exteroreceptors: on external surface of body (cutaneous receptors) B) Interoreceptors: Inside the body e.g. baroreceptors, proprioceptors C) Teloreceptors : which detect distant signals(visual and auditory receptors) III. Depending upon adaptation of receptors A) Rapidly adapting (Phasic) receptors. e.g. hair end organs, pacinian corpuscles, olfactory receptors,missner's corpuscles. B) Slowly adaptating or non-adapting (tonic) receptors. e.g. pain receptors, baroreceptors. PROPERTIES : i) Specificity or differential sensitivity(Law of adequate stimuli): Each receptor is, stimulated only, by its specific stimulus. For example, specific (adequate and appropriate) stimulus for rods and cones is light, for pacinian corpuscle, is pressure and so on. However some receptors respond to high strength stimuli of other type. ii. Adaptation of a receptor: If a receptor is stimulated continuously, then after sometime, the impulse rate through afferent nerve fibers goes on Decreasing and may stop completely. This is called adaptation of receptors. Various mechanisms that causes adaptation are: a) Reorientation of receptor structure e.g. in pacinian corpuscles, the concentric layers near the nerve terminal slip back to their original position thus removing the distorting force. b) By changing the sensitivity of the receptors as in case of rods and cones (dark adaptation). c) Central adaptation as occurs in olfactory pathway. d) Accommodation of nerve fiber to receptor potential due to exortion of neurotransmitter. iii) Recruitment: As the strength of the stimulus is gradually increased, initially low threshold receptors and then with higher strengths, higher threshold receptors are stimulated. Also the adjacent receptors are stimulated with strong stimuli. Thus as strength of stimulus increases, more receptors are recruited. iv) Inhibition of receptors: In some sensory tracts there are efferent (corticofugal) fibers which end around receptors and modify their sensitivity e.g. in auditory pathway these fibers decrease sensitivity of some couters hair cells so that attention can be directed to another sound of a perticular frequency. v) Impulses arising from specific receptors pass through a discrete tract carrying a specific modality of sensation and having a specific termination in brain. This is known as Labeled line principle. It helps in Suggestions: facebook.com/asifpatel.ggmc

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detecting modality of sensation and also site of sensation. As sensation perceived in brain is always projected to the site of receptors. This is called Law of projection. vi) Encoding of intensity of stimulus by receptors: intensity of stimulus strength is transmitted in 2 forms : 1) by frequency of impulses along afferent nerve. 2) by the number of receptors stimulated. Discrimination of intensities of two or more stimuli is explained by: 1) Weber-Fechner Law which, states that intensity perception is proportional to logarithm of original strength of stimulus. 2) Power Law which states that intensity of a sensation perceived is proportional to a certain (constant) power of strength of stimulus. Excitation of a receptor:

When a touch or pressure stimulus is applied to Pacinian Corpuscle, there is distortion of membrane of nerve terminal leading to opening of Na+ channels and Na+ influx. The resulting decrease in the receptor negativity is called Receptor Potential which then generates action potential at the first node of Ranvier of afferent nerve. The amplitude of receptor potential is directly proportional to the strength of stimulus while the frequency of action potentials in the afferent nerve is directly, proportional to amplitude of receptor potential.

*Q. DESCRIBE THE DORSAL COLUMN PATHWAY AND ITS FUNCTIONS: Dorsal column pathway is a group of afferent fibers ascending through dorsal column of spinal cord and then through medial lemniscus. Course : First order neuron in the pathway is the dorsal root ganglion cell. The peripheral process of this cell arises from various mechanoreceptors like Meissner's Corpuscles, Merkels’ discs, Pacinian corpuscles, hair end organs etc. The Central process enters the spinal cord through dorsal root & divides into medial and lateral branch. The medial branch ascends through the dorsal column of spinal cord all the way and end in dorsal column nuclei situated in medulla. Fibers coming from lower half of body (Below T6) pass through Fasciculus Gracilis (tract of Gall) situated medially in spinal cord and end in nucleus Gracilis, while those from upper half of body ascend through Fasiculus cuneatus (tract of Burdach) and end in nucleus cuneatus. 2) Second order neurons are the neurons of these nuclei, some of the fibers arising from these neurons pass into the cerebellum (dorsal and ventral external arcuate fibers) while others cross to the opposite side (internal arcuate fibers) and ascend through medial lemniscus which is joined by fibers coming from main sensory nucleus of trigeminal nerve carrying sensation from face. The medial lemniscus ends in ventral posterolateral nucleus while the trigeminothalamic fibers end in ventral posteromedial nucleus of thalamus 3 ) Third order neurons are the cells of these nuclei whose fiber pass through the post. limb of internal capsule and end in somatic sensory Area I(areas 3, 1, 2) situated in posterocentral gyres. Some fibers also end in somatic sensory area II situated below and behind area I in parietal lobe. The somatosensory Cortex I has topographical representation of various parts of the body on opposite side (Sensory homunculus). Sensory fibers from foot region end in upper medial part of sensory cortex, while those Suggestions: facebook.com/asifpatel.ggmc

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122 from face end in lower part. Areas of the body which are more sensitive (containing more receptor) e.g. lips, face, fingers etc. have larger representation in sensory cortex. FUNCTIONS : Dorsal column pathway carries following sensations: 1. Finer aspects (epicritic) of touch sensation like tactile localization (topognosis) and tactile discrimination. 2. Finer aspects of pressure sensation which enables perception of smell, differences in weight. 3. Conscious proprioceptive sensation, including joint-position sensation and sensation of movement (Kinaesthetic sensation) 4. Sensation of vibrations. 5. Stereognosis i.e. ability to indentify an object by its size, shape, texture and previous knowledge. Special features of Dorsal Column Pathway: 1. This pathway is of recent origin in evolutionary scale than anterolateral pathway. 2. It carries only mechanoreceptive sensation. 3. It is made up of large myelinated fibers with fast conduction. 4. There is high degree of spatial orientation of fibers in this pathway. 5. Carries finer aspects of sensation. Applied physiology: In diseases like tabes dorsalis or subacute combined degeneration of spinal cord, there is damage to this pathway resulting in loss of fine touch, fine pressure, proprioception and vibration sensation.

*Q. DESCRIBE THE PATHWAY OF PAIN SENSATION. Defn: Pain is defined as the psychical adjunct of an impending tissue damage. It is a protective sensation. Receptors for pain, (nociceptors) are the free nerve endings which can be stimulated by mechanical, thermal, chemical stimuli. They are situated in skin, subcutaneous tissue, periosteum, visceras etc. and are nonadapting in nature. There are 2 types of pain: i) Fast pain or pricking pain or sharp pain which occurs within 0.1 Sec of injury and ii) Slow pain or aching pain, or burning pain, which begins after a second and persists for minutes or hours. Pathway of Fast Pain (Neospinothalamic pathway) :- It transmits mechanical and thermal pain. It is made up of A δ fibers (2.5 microns in diameter) with conduction velocity of 6-30m/s. The first order neuron is the dorsal root ganglion. Peripheral process arises from pain receptors. Its central process enters the spinal cord through posterior root, ascends or descends for one or two segments forming tract of Lissauer, and ends on neurons of lamina I (Lamina marginalis) of dorsal horn. Axons of, these second order neurons cross immediately to opposite side through anterior commisure and ascend through lateral column of spinal cord. In the medulla they, pass though spinal lemniscus, give collaterals, to reticular formation of medulla, Pons and midbrain and end in ventrobasal complex (VPL and VPM nuclei) and posterior nuclear group. Third order neurons then project to the somatosensory cortex in postcentral gyrus. Importance of fast pain: 1. Immediately informs the brain about presence of harmful stimulus and elicits withdrawl reflex. 2. Helps in localisation of pain. Slow Pain pathway (Paleospinothalamic Pathway): It is the primitive system for pain transmissions. It is made up of dorsal root C fibers (0.5 to 1 micron in diameter) with conduction velocity of 0.5-2 m/s. Here, the central process of dorsal root ganglion cells passing through tract of Lisseuer ends on neurons of laminae II and III (substantia gelatinosa) of dorsal horn. Axon of these neurons project to neurons in layer V which forms third order neurons. Their axons cross immediately to opposite side through anterior commissure (few do not cross) and ascend through lateral column of spinal cord. These fibers end in 1. Reticular nuclei of medulla, pons Suggestions: facebook.com/asifpatel.ggmc

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and midbrain. 2. Periaqueductal grey matter. 3. Tectal area. 4. Intralamnar nuclei of thalamus. This pathway does not go to cerebral cortex. Importance of slow pain: 1. It indicates that pain perception can occur in subcortical structures. 2. It continues as long as there is tissue damage. 3. It brings about activation of Reticular Activating System(RAS) Applied Aspects:- Pain is the most important sensation clinically. Certain visceral pain is characteristic. Eg. angina pectoris, renal, colic etc. Pain can be controlled by use of analgesic, counterirritants, acupuncture (which block the entry of pain at substantia gelatinosa gate control mechanism) or by anterolateral cordectomy, epidural anaesthesia.

DESCRIBE THE ORIGIN, COURSE AND FUNCTIONS OF CORTICOSPINAL TRACTS. ORIGIN: 1) 30% fibers of corticospinal (Pyramidal) tract arise from Primary motor cortex situated in precentral gyrus (area 4). This area has an inverted representation of different muscles (motor humunculus) of the opposite side of body. Those parts of the body concerned with fine skilled movements like fingers, tongue etc. have larger representation. 2) 30 % Fibers arise from Premotor area (Area 6 situated in front of precentral gyrus) and from Supplementary motor area extending onto medial surface of cerebral hemisphere. 3) Remaining 40 % fibers arise from somatosensory cortex I (areas 3,1, 2) and from somatic association areas (5,7) of parietal lobe. Course: Fibers arising, from these areas pass through the corona radiata to the internal capsule. Here, the corticonuclear fibers occupy the genu while corticospinal fibers occupy anterior 2/3 of posterior limb of internal capsule. The tract rotates through 90°, so that head fibers are situated anteriorly, and leg fibers posteriorly. The fibers pass through crura Cerebri of midbrain occupying middle 3/5th of crus. Here, the head fibers are situated medially and leg fibers laterally. In the pons, fibers are scattered into discrete bundles passing through ventral aspect of pons. In the medulla fibers form compact bundles which produce a pyramid-shaped elevations on ventral aspect of medulla. Also they arise from pyramidal cells of cortex mainly. (Hence called pyramidal tracts). As the tract descends through midbrain, pons and medulla, the corticonuclear fibers end on the motor nuclei of cranial nerves on opposite side. At the lower Part of medulla about 80 % fibers, cross to the opposite side, turn backwards and descend through lateral column of spinal cord as Lateral corticospinal (crossed pyramidal) tract. About 15 % fibers do not cross in medulla and descend in anterior column of sp. cord forming Ventral CorticoSpinal (uncrossed pyramidal) tract. However, these fibers cross through the anterior commissure of spinal cord in Cervical and thoracic segments. Some uncrossed fibers descend through lateral column forming uncrossed lateral corticospinal tract. Termination: Majority of corticospinal fibers end on interneurons, in intermediate zone of spinal gray matter which then terminate on motor neurons. Few fibers, especially in cervical region terminate directly on motor neurons. 55% fibers of pyramidal tract end in cervical region, 20 % in thoracic region and 25% in lumbosacral regions of spinal cord. Functions: 1. This pathway is responsible for initiation and control of voluntary movements on the opposite side of the body, especially fine, skilled purposeful movements involving fingers and distal joints. It executes various movements that are programmed in various motor areas of the brain like premotor area, sensory area, basal ganglia, cerebellum etc. 2. It forms pathway of superficial reflexes like plantar reflex, abdominal reflexes etc. 3. It has facilitatory influence on spinal motor neurons. Suggestions: facebook.com/asifpatel.ggmc

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124 Applied Physiology : Selective damages to pyramidal tract produces 1.loss of fine movements on opposite side 2. Hypotonia 3.Loss of superficial reflexes 4. Sluggish deep reflexes. 5. Babinsky sign present.

Q. DESCRIBE EXTRAPYRAMIDAL TRACTS AND THEIR FUNCTIONS Defn: Extrapyramidal tracts are the descending tracts other than the pyramidal tracts. They provide an alternate pathway for control of voluntary and reflex activities. They include A. Rubrospinal tract Origin :- From red nucleus in the midbrain it receives fibers from primary motor cortex (corticorubral) and dentate nuclei of cerebellum and nucleus interpositus. It has topographical representation of body, muscles. Course : Fibers cross in the midbrain to opposite side (Forels decussation), and descend through pons, medulla and then through lateral column of spinal cord anterior to crossed pyramidal tract. It extends only upto thoracic segments. Termination : Ends on interneurons in intermediate zone of spinal gray matter. Functions: 1. Controls fairly discrete voluntary movement of wrist joints. Thus it is functionally similar to pyramidal tracts 2) Has facilitatory influence on spinal motor neurons. B) Reticulospinal tracts : i) Pontine (Medial) reticulospinal Tract: Origin: from nuclei pontis reticularis oralis and caudalis. These neurons have intrinsic excitability and are driven by a) Vestibular nuclei b) cerebellar nuclei and c)RAS Course and termination: Fibers descend through ventral column of spinal cord on same side and end on medial motor neurons (alpha and gamma) of anterior horn, especially those supplying antigravity extensor muscles. Functions :-This tract has facilitatory influence on motor neurons of antigravity muscles and thus helps to maintain erect posture. ii) Medullary (Lateral) reticulospinal tract: Origin: from nuclei reticularis gigantocellularis, in medulla which receives inputs from a) Motor cortex (4s) b) Caudate nucleus and c) Cerebellum Course and termination: Fibers arise from both sides and descend through lateral column of spinal cord and end on medial motor neurons of anterior horn. Function: It has inhibitory effect on anti-gravity extensor muscles & -thus decreases their tone so that movements can be carried out. Besides these functions, reticulospinal tracts also transmit descending impulses concerned with a) regulation of respiration. b) regulation of vasomotor tone and blood pressure. c) Regulation of GIT function. C) Vestibulospinal tracts : i) Lateral Vestibulospinal tract: Origin : from lateral Vestibular(Deiter's) nucleus which is intrinsically excitable but its activity is suppressed by cerebellar nuclei. It also receives inputs utricula and saccule. Course- Fibers descend through anterior column of cord on same side and end on medial motor neurons, especially alpha Motoneurons. Functions: It has facilitatory, influence on motor neurons supplying axial and girdle muscles. ii) Medial vestibulospinal tract : Origin : from medial Vestibular nucleus which receives inputs from semi circular canals. Course: Fibers descend through medial longitudinal fasciculus giving collaterals to vomiting centre, salivary nuclei etc- and end on cervical motoneurons. Functions : 1) Reflex responses such as nausea, vomiting, salivation etc. due to stimulation of Vestibular apparatus 2) Appreciate movements of head and neck in response to vestibular stimuli. D) Tectospinal tract : Origin: from superior and inferior colliculus. Suggestions: facebook.com/asifpatel.ggmc

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Course and termination: Fibers cross to opposite side in midbriain decend through pons, medulla and ant. column of spinal cord and end on cervical motoneurons. Functions : Reflex adjustments in tone and posture in response to visual and auditory stimuli. E) Olivospinal tract: Origin: Arises from inferior olivary nucleus, descends through anterior column of spinal cord and ends on Anterior horn cells.

OVERALL FUNCTIONS OF EXTRAPYRAMIDAL SYSTEM It is a primitive motor system mainly arising from subcortical motor areas. It arises from 1) Premotor area 6 and area 8. 2) Red nucleus 3) Basal ganglia 4) Motor nuclei of reticular formation of brainstem 5) Vestibular nuclei. By exerting facilitatory and inhibitory influences over spinal motor neurons, Extrapyramidal system performs various functions like 1. It regulates muscle tone and sensitivity of tendon reflexes by controlling activity of gamma motor neurons 2. It maintains posture and equilibrium by regulating tone of antigravity extensor muscles. 3. It is concerned with regulation of gross voluntary movements involving proximal joints of limbs and axial and girdle muscles. 4. It controls automatic and associated movements like swinging of arms while walking. 5. It maintains background postural fixations such that pyramidal tract can carry out fine, skillful movements of distal joints.

*Q. DISCUSS THE ROLE OF MUSCLE SPINDLES IN MAINTAINING MUSCLE TONE : Def : Muscle tone is a state of partial and sustained contraction of a muscle even in resting state. It is a reflex process and results from continuous asynchronus discharge of motor neurons, which results from stream of impulses coming from muscle spindles.MUSCLE- SPINDLE is a spindle - shaped encapsulated structure, about 10 mm long and 100 microns in diameter situated along (parallel) the length of muscle and attached at either ends to extrafusal fibers. It is made up of about 2-12 slender intrafusal fibers which are of 2 types: 1) Nuclear bag fibers in which nuclei produce a bulge in the centre and 2) nuclear chain fibers in which nuclei are arranged in the form of chain. When intrafusal fibers contract, shortening occurs at polar ends leading to stretching central portions. Innervation : A) Afferents: 2-types of afferents arise from muscle spindle 1)Primary or annulospiral endings which arise from and encircle central portions of nuclear bag and chain fibers. Their fibers are large ( Ia type) and transmits impulses faster(72-120 m/s) They enter spinal cord through dorsal root and end on alpha neurons supplying extrafusal fibers of that muscle. Function: These ending give information of change in length and rate of change in length of muscle fiber (dynamic response) 2) Secondary or flower spray endings : Arise from nuclear chain fibers and their impulses are carried through Group II fibers which are thin and conduct slower (3-70 m/s) They inform about change in length of muscle (static response. B) Efferents :- Intrafusal fibers are innervated by Gamma neurons of spinal cord. There are 2 types of gamma efferent fibers i) Gamma dynamic fibers which end on nuclear bag fibers (plate endings) and sensitize the dynamic response of muscle spindle. ii) Gamma static fibers and nuclear chain fibers (trail endings) and sensitize static response. Mechanism of Muscle tone: Normally even in resting state, there is a continous discharge of impulses going from gamma motor neurons through the gamma efferents intrafusal fibers. Contraction of polar ends of intrafusal fibers causes stretching of central portion of nuclear bag as well as nuclear chain fibers, leading to distorsion of annulospiral endings and generation of receptor potentials. Impulses are carried through Ia afferents to alpha motor neurons in spinal cord which then send impulses through alpha efferent fibers to extrafusal muscle fibers causing their contraction. This state of partial and sustained contraction of muscle even at rest is the muscle tone. Thus the muscle tone depends upon Gamma efferent discharge. When the discharge increases, muscle tone increases (hypertonia) and when it decreases, tone also decreases (hypotonia). Suggestions: facebook.com/asifpatel.ggmc

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126 Gamma, discharge increases sensitivity of muscle spindles. Stretching of muscle also causes stimulation of muscle spindle receptors and shortening of muscle (stretch reflex). Thus muscle spindle also maintains the tone of muscles and also the length of muscle. Since this mechanism of maintenance of muscle tone operates via pathway of stretch reflex, it is also known as Myotactic mechanism. Applied physiology: Cutting of dorsal nerve root (deafferentation) or lower motor neuron lesion causes loss of muscle tone. In Parkinsons disease or after decerebration, gamma discharge increases leading to rigidity.

*Q. DESCRIBE THE SUPRASPINAL CONTROL OF MUSCLE TONE: Muscle tone, is a state of sustained and partial contraction of muscle even in the resting state. It is a reflex process and results from continuous discharge from spinal motor neurons. Spinal control: at the spinal cord level, discharge from gamma motoneurons causes contraction of intrafusal fibers of muscle spindles and stimulation of annulospiral endings. Afferent impulses pass through Ia fibers stimulating alpha motoneurons which leads to contraction of extrafusal muscle fibers i.e. muscle tone Supraspinal control: The spinal motoneurons are under the influence of impulses coming from higher centres: There are 2 areas in the brain stem which influence the activity of gamma neurons: 1. Pontine reticular facilitatory area : situated in reticular formation of pons. Fibers arising from this area descend through pontine-reticulospinal tract and they have excitatory influence on gamma motoneurons. This area is either intrinsically active or is activated by reticular activating system. 2. Bulbar inhibitory area: situated in reticular formation of medulla. Its fibers descend through medullary reticulospinal tract and they have inhibitory influence on gamma neurons. This area is not intrinsically active but is driven by impulses coming from a) Suppressor area of motor cortex (areas 4, 5 and 6) b) basal ganglia especially the caudate nucleus and c) anterior lobe of cerebellum (in animals). In addition to these areas, the vestibular nuclei (esp. lateral) in the medulla have influence on, spinal motoneurons. These nuclei are intrinsically active and fibers arising from them pass through vestibulospinal tract and terminate on gamma as well as alpha neurons. They have excitatory effect, on these neurons. However their activity is suppressed by impulses coming from anterior lobe of cerebellum in animals (In human beings neocerebellum, especially dentate nucleus has facilitatory influence on muscle tone and removal of cerebellum produces hypotonia. Thus normally there is a balance of excitatory and inhibitory impulses converging on spinal motoneurons(esp. gamma ), with slight excitation of gamma neurons leading to resting muscle tone. Any factor that shifts the balance towards excitation increases muscle tone or towards inhibition decreases it. Factors affecting activity of gamma neurons :1. Postural reflexes: -like tonic neck reflexes, righting reflexes etc. which are mediated through extrapyramidal pathways bring about alteration in muscle tone to maintain posture. 2. During sleep, activity of pontine facilitatory area is decreased due to inactivation of RAS, therefore gamma motor neuron discharge decreases. 3. Higher centre’s:- Emotions like anxiety and tension increase gamma activity and muscle tone. 4. Impulses from peripheral receptors:- And stimulate gamma neurons e.g. interlocking of fingers facilitates stretch reflex (Jendrassik’s maneuver).

Applied aspects :- Transection of brain stem at the level of superior colliculus(Sherrington's) removes two of the three areas driving bulbar inhibitory area leading to facilitation of gamma neurons and decerebrate rigidity. *Q. Define and Classify Reflexes; Describe Any Three Properties of Reflex Action:

Def: - Reflex action is automatic, spontaneous, involuntary motor response to a sensory stimulus. The through which reflex action is mediated is known as Reflex arc. Classification of Reflexes :-

A) Clinical Classification:- 1. Superficial reflexes (e.g. cornmeal reflex). 2. Deep reflexes (tendon reflexes like biceps jerk, knee, jerk etc.) 3. Visceral reflexes (papillary reflex). Suggestions: facebook.com/asifpatel.ggmc

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B) Anatomical Classification:- 1. Segmental reflexes (stretch reflex). 2. Intersegmental reflexes (crossed extensor reflexes, locomotion reflexes). 3. Suprasegmental (postural reflexes). C) Developmental Classification:- 1. Present at birth (Unconditioned reflexes e.g. tendon reflexes). 2. Acquired after birth (conditioned reflexes e.g. salivary secretion in response to sight, smell or thought of food. D) Depending on level of centre: 1. spinal reflexes (stretch reflex) 2. bulbar reflexes (salivary, vomiting reflex). 3. Mesencephalic reflexes (pupillary). 4. Cortical reflexes (optical righting reflex).

E) Depending upon number of synapses. 1. Monosynaptic reflexes (stretch reflex). 2. Multisynaptic reflexes (withdrawal reflex). F) Physiological classification. 1. Flexor reflexes (withdrawal reflex). 2. Extensor reflexes (crossed extensor reflex.) Properties of Reflex Action:

1. Summation:- It the appearance of reflex response following application of two or more sub minimal stimuli. The stimuli may be applied at the same of afferent fiber one after the other leading to a type of summation called Temporal summation. (Summation with respect to time). Or the stimuli may be applied simultaneously on two or more afferent fibers converging. (Spatial Summation i.e. Summation with respect to space). Summation results from addition of excitatory post synaptic potentials (EPSPS) on the neurons of reflex centre. 2. Subliminal fringe: - It the greater reflex response obtained on simultaneous stimulation of 2 or more afferent neurons as compared to the sum total of their responses when stimulated separately. Suppose stimulation of afferent neuron, A causes adequate stimulation of neuron X but only partial excitation of neuron Y. Hence only one afferent neuron gives response. Similarly stimulation of afferent neurons B causes adequate excitation of neurons Z but only partial excitation of Y. Therefore sum total of individual stimulation will be X Z. On the hand, if A and B are simultaneously stimulated not only neurons X and Z will respond, but neuron Y will also be stimulated due to addition of EPSPS. (Spatial summation) and the number of responding neurons will increase (X+Y+Z). 3. Irradiation: - If a weak sensory stimulus is applied the reflex response will be less and localized. But is a strong stimulus is applied, impulses spread to adjacent neurons in the centre producing stronger and wider response. This is called irradiation. For example a slight pin prick to a finger will cause withdrawal of finger, but a strong prick will cause withdrawal of whole arm or entire body. Other properties include 4. Delay (reflex time) 5. Occlusion. 6. Facilitation. 7. Inhibition. 11. Fatigue. 12. Localization (local sign). 13. Rebound phenomenon. *Q. Describe The Mechanisms That Maintain Posture OR Describe various Postural Reflexes:

Def :- Posture is the position of different parts of the body in relation to one another and in relation to space, brought about by subconscious reflex adjustment in the tone of different muscles, so as to maintain equilibrium and to provide background for carrying out smooth and purposeful movement .

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128 Postural Reflexes

Static reflexes

Stetokinetic reflex

Ocal static

Positive Supporting

General Static

Exaction

Negative Supporting Exaction

Segmental static Stretch reflex -

Cortical reflexes

- Hopping reaction

Flexor reflex

Reaction to

Crosses extensor reflex

Attitudinal reflexes - Tonic neck reflex.

- Tonic Labyrinthine reflex

- Placing

Movement.

Reaction

Rotation.

Righting reflexes - Labyrinthine righting reflex

- Neck righting reflex & Optical righting reflex

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1. The basic postural reflex is the stretch reflex:- Human body has a multi jointed structure and there is as sagging tendency at each joint because of gravity. This tendency causes stretching of muscle spindles of antigravity muscles, impulses pass through I afferents to alpha motoneurons causing contraction of these muscles so that upright posture is maintained. Other postural reflexes adjust the tone (Sensitivity of stretch reflex) of muscles by modifying discharge to gamma motoneurons mainly via extra pyramidal pathways. Other postural reflexes:

2. Positive supporting reaction (Magnet reaction): Stimulus: - Pressure on foot pad or sole (contact with ground) Receptors: Proprioceptors in foot Response :- Contraction of flexors and extensors of limb to support the body. Centre- sp cord. 3. Negative supporting reaction :- Stimulus : Removal of pressure from foot (lifting of limb from ground) Response: Inhibition of flexors as well as extensors so that limb can be moved to a new position. Centre : sp. cord.

4. Tonic Neck reflexes:- Stimulus :- Change in position of head relative to body. a) when head is turned to one side – extension of limb on that side and flexion of opposite limb. b) Ventroflexion of neck flexion of forelimbs and extension of head- extension of forelimbs flexion of hind limbs. Receptors: Proprioceptors in neck muscles. Centre: Cervical sp. cord and medulla. 5. Tonic extensor tone when animals in supine and decreased extensor tone in prone position. Receptor: Otolith organs. Response: Righting of head. Centre: midbrain. This reflex is responsible for righting when a person dives into water. 7. Neck righting reflex: Stimulus: stretching of neck when the body is not is alignment with head Rcpt. : Muscle spindles in neck muscles. Resp: righting of thorax and pelvis Centre: midbrain.

8. Body on head righting reflex : Stimulus: Pressure on one side of body. Rcpt. Cautious receptors. Resp: Righting of head Cent: Midbrain.

9. Body on body righting reflex: Stimulus: pressure on one side of the body. Receptor: Cutaneous. Resp: righting of body. Centre: midbrain.

10. Visual (optical) righting reflexes : Stimulus: abnormal position of head in space detected by visual receptors (rods and cones) Resp. Righting of head and then of body. Cent: Visual cortex. This is the most important righting reflex in man which maintains equilibrium while carrying out daily activities. 11. Placing reactions: Resp: limb is placed firmly on supporting surface to support the body in response to a) cutaneous impulses contact placing reaction b) visual impulses visual placing reaction c) vestibular impulses- vestibular placing reaction. Centre- cerebral cortex.

12. Hopping reaction: Stimulus: sudden lateral push to standing animal. Receptor: Muscle spindle Resp: Hopping movements that keep the limbs in position to support the body. centre: Cerebral cortex. *Q. Describe The Functions of Vestibular Apparatus:

Vestibular apparatus consists of semicircular canals, utricle and saccule.

Semicircular canals: on each side, horizontal, superior and posterior, arranged at right angles to each other. Each canal is filled with viscous endolymph and has a dilated ampulla at one end. The ampulla contains hair cells whose cilia are embedded in gelatinous cupula. Suggestions: facebook.com/asifpatel.ggmc

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130 Utricle and saccule :- are chambers of membranous labyrinth filled with endolymph. The receptors are hair cells in macula. Their cilia project into the gelatinous monolithic membrane containing otoliths. Entire structure is called otolith organ. Function of Semicircular canals:-

1. Detection of angular (rotational) acceleration and deceleration: when head starts rotating, say in horizontal plane, the endolymph in horizontal canal lags behind because of its inertia. This causes displacement of copula and bending of cilia. If this bending is in the direction of Kino cilium, the discharge rate through vestibular nerves increases. With continued rotation at same speed, copula comes back to original position rotation and the vestibular nerve discharge comes to normal. When rotation stops suddenly, endolymph continues to move (membrane) displacing copula to other side and vestibular nerve discharge is reduced. Thus brain is informed about beginning and end of rotation. 2. Predictive function:- semicircular canals can predict ahead of time if malequilibrium will occur during a turning movement and bring about appropriate correction. 3. Vestibulo-ocular reflex:- Is a reflex that maintains visual fixation on stationary points when the head rotates. This movement is the slow component of nystagmus. Impulses, arising from semicircular canals pass into vestibular nuclei and then through medial longitudinal fasciculus to the III, IV and VI cranial nerve nuclei for this reflex. Functions of utricle and Saccule :- 4. Otolith organs give information about position of head in relation to gravity, those in utricle inform about forward or backward bending of head and those in saccule, about lateral bending. When the head is bent, gravity acting on otoliths causes displacement of otolithic membrane and bending or cilia leading to stimulation of hair cells. Thus in each position of head, some hair cells are stimulated and this ‘Pattern’ of excitation informs the brain about position of head. 5. Information about linear acceleration: - When body suddenly accelerates forwards, otolithic membrane falls backwards over macule causing bending of cilia and stimulation of hair cells. Other functions of vestibular apparatus: - 6. Maintenance of tone and posture: Vestibular apparatus by sending impulses to vestibular nuclei and then about subconscious adjustments in tone and posture in response to change in position of head or in response to linear and rotational acceleration. 7. It is also responsible for initiating righting reflex, for tonic labyrinthine reflexes and also for landing on all four limbs in blindfolded animals (vestibular placing reaction). Applied aspects: - Streptomycin toxicity affects vestibular functions. Motion sickness results from excessive stimulation of vestibular apparatus. *Q. Describe The Connections, Function of cerebellum And Manifestations of Cerebellar Dysfunction:

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Connections:

A) Afferent Fibers :- a) Those passing through inferior cerebellar peduncle. 1) Dorsal spinocerebellar tract: Carries subconscious proprioceptive fibers:- form lower part of body on same side. 2. Cuneocerebellar fibers:- from accessory cuneate nucleus, carry subconscious proprioception from upper limb. 3. Vestibulocerebellar fibers: arising from vestibular apparatus and vestibular nuclei and in floculonodular lobe for maintenance of equilibrium. 4. Olivocerebellar fibers :- arise from inf. olivary nucleus and relay impulses from motor cortex. 5. External actuate fibers : arise from dorsal column nuclei and relay proprioceptive and cutaneous impulses. 6. Reticulocerebeller fibers. 7. From 5th, 9th and 10th cranial nerves. b) Through middle cerebellar peduncle:

8. Pontocerebellar fibers: - arise from pontine nuclei and relay motor impulses from corticospinal tracts to middle lobe of cerebellum. 9. Cerebellocerebellar fibers- from one lobe of cerebellum to another. C) Through superior peduncle:

9. Ventral spinocerebellar (Gower’s) tract: carries reference copy of motor impulses going to lower limbs to both sides of cerebellum. 10. Rostral spinocerebellar fibers : from upper limbs same function. 11. Tectocerebellar tracts: arise from sup and inf. colliculi and convey visual and auditory impulses. Efferent fibers:- a) Through inferior peduncle.1. Fastigiobulbar tract: - to vestibular nuclei from which vestibulospinal tract arises. 2. Cerebelloolivary fibers to inf. olivary nucleus.

b) Through superior peduncle: 3. Cerebellothalamocortical fibers:- arise from nucleus interpositus and pass to opposite, anterior and ventrolateral nuclei of thalamus and then to motor cortex. 4. Dentatorubrothalamic fibers: from dentate nucleus to red nucleus and then to motor nuclei of thalamus. Functions:

A) Role in control of Voluntary movements: - Cerebellum controls rate, range, force and direction of voluntary movements on the same side of the body. (ipsilateral control).

Functions of intermediate zone: 1. Error control function: During movement cerebellum gets information about ‘intentions’ of motor cortex through corticopontecerebeller fibers and about ‘Performance’ through spinocerebellar tracts. If there is any ‘error’ (discrepancy), cerebellum sends corrective impulses back to motor cortex via motor relay nuclei in thalamus. 2. Damping function : Normally at the beginning of a rapid voluntary Movement, motor cortex sends more impulses to overcome inertia. Therefore there is tendency to overshoot the point of intention. This is detected by cerebellum and it sends inhibitory impulses to motor cortex to stop the movement exactly at the intended point. Damping also prevents occurrence of pendular movements.

3. Co-ordination agoniste and antagonist: - At the beginning of a movement, cerebellum causes 'turn on' of agonist and ‘turn off’ of antagonist. Then when the movement reaches the point of intention, it causes reversal of excitation i.e. turn off of agonist and turn on of antagonist muscles. Suggestions: facebook.com/asifpatel.ggmc

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132 4. Control of ballistic movements: - Such as typing, saccadic eye movements, alternate suspiration and probation etc. This is due to circuitry in cerebellum in which signals first excite deep nuclear cells and then inhibit these cells a few milliseconds later through Purkinje cells.

5. Alpha Gamma co activation: - Cerebellum also causes co-activation of alpha and gamma neurons during a voluntary movement so that muscle spindle sensitivity is maintained throughout the movement. Function of lateral zone: 6. Planning and programming function: - It plans the timing and sequencing of complex voluntary movements which are finally executed by motor cortex. (Action potentials have been observed in lateral zone before the beginning of a movement). 7. Motor predicative function :- Cerebellum can predict ahead of time the position of different parts of the body so that a subsequent movement can be initiated from that point. This is prediction: It can also predict progression of on approaching visual or auditory stimulus. B) Role in involuntary movements :-

8. Maintenance of tone :- In human beings neocerebellum and dentate nucleus have facilitatory influence on spinal motoneurons and tend to increase muscle tone.

9. Maintenance of posture and Equilibrium :- Archicerebellum (flocculonodular lobe) gets information about head position and rotation from vestibular apparatus while paleocerebellum gets information about position of different parts of body and tone of muscle through spinocerebellar pathways. These areas then send afferents through reticulospinal and vestibulospinal tracts and bring about contraction of appropriate muscle to maintain equilibrium and posture. Manifestations of Cerebellar Dysfunctions:-

Result from tumor, trauma or thrombosis. They are seen on the same side of lesion and are usually seen only when large portions of cerebellum are damaged. I. Manifestations affecting voluntary movements :-

1. Ataxia :- Non-coordination of movements due to error in rate, range, force and direction of movement. It is a motor ataxia not affected by closure of eyes. 2. Dysmetria and past pointing :Movements fail to reach intended point or overshoot beyond the point of intention. 3. Decomposition of movements in which movements. are carried out in steps one joint at a time, due to failure of smooth progression of movements. 4. Adiadochokinesis is inability to carry out rapid alternate movements like pronation and supination, due to asynergia between agonists and antagonists. 5. Intentional (action) tremors: - Appear while performing specific voluntary activity due to failure of damping function. 6. Dysarthria: Scanning speech, in which words are split into separate syllables, is due to lack of co-ordination and failure of smooth progression of muscles of articulation. 7. Nystagmus:- is to and fro movt of eye balls seen when looking at object that is placed laterally. It is due to failure of damping. 8. Rebound phenomenon: is inability to control a movt. when resistance is suddenly removed, results from failure of braking (reversal of excitation) effect. II. Manifestations affecting tone, posture and equilibrium: 9. Hypotonic :- results from loss of facilitation of motor cortex and brain stem nuclei by deep nuclei of cerebellum. 10. Pendular knee jerk- due to hypotonic and loss of damping. 11. Defective posture : due to hypotonic 12. Loss of equilibrium and tendency to fall if there is damage to flocculonodular lobes. 13. Staggering or reeling gait with feet wide apart due to loss of equilibrium. Suggestions: facebook.com/asifpatel.ggmc

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*Q. Describe The Connections And Functions of Thalamus:

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Thalamus is a large mass of neurons situated one on each side deep in the cerebral hemispheres. Connections:

A) Afferents: 1. Through medial lemniscus: fiber arising from peripheral parts of body carrying fine touch, vibration, proprioception etc. Relay in ventral posterior lateral nucleus. 2. Spinal lemniscus: fibers from spinothalamic tracts carrying crude touch, pain and temp are also relayed in VPL nucleus. 3. Trigeminal lemniscus: - general sensory fibers from face and taste fibers are relayed to ventral poster medial nucleus. 4. Mamillothalamic tract : arising from mamillary nuclei of hypothalamus ends in ant. nucleus of thalamus. It forms part of Papez circuit of the limbic system. 5. From cerebellum: fibers from nucleus interpositus are relayed in ventral ant and ventral lateral nucleus. 6. Rubrothalamic fibers from red nucleus are relayed in VA and VL nuclei. 7. Corticothalamic fibers arising from frontal, prefrontal cortex and in medial dorsal and lateral dorsal nucleus. 8. Pallidothalamic fibers from globus Pallidus to VA and VL nuclei. 9. From Reticular formation to midline and intralminar nuclei 10. From lat. olfactory stria to medial dorsal nucleus (new pathway). Optic tract into lateral geniculate body 12. Auditory fibers into medial geniculate body. Efferents: -1. Though specific thalamocortical pathways:-

a) general sensory fibers are relayed from VPL and VPM nuclei to somatic sensory fibers cortex (3, 1, 2) b) gustatory fibers are relayed to operuculoinsular cortex. c) LGB to primary visual cortex. d) Olfaction fibers to orbitofrontal cortex. 2. Diffuse thalamocortical fibers arising from midline and intralaminar nuclei and project diffusely to cerebral cortex. 3. Form Ant nucleus to cingulated gyros (limbic function) 4. To Neostratum from Centromedian nucleus. 5. to ant nuclei of hypothalamus from medial dorsal nucleus. Function of Thalamus :-

1) Acts as Relay station for all types of sensory impulses (as mentioned in specific pathways above). 2. Acts as centre for perception of burning type of pain, which terminates in midline are intralaminar nuclei of thalamus. 3. Centre for perception of crude (protopathic) sensations like crude touch (high threshold, poor localization poor discrimination) 4. Role in wakefulness and alertness: Diffuse thalamocortical fibers arising from midline and in turn, activate large portions of cerebral cortex and bring about arousal response, wakefulness and alertness. 5. Motor Cerebellum, red nucleus and basal ganglia (forming a part of caudate circuit and putamen circuit) and project to motor cortex, premotor, prefrontal and supplementary motor area. Thus thalamus forms a component of the pathway which controls voluntary movements of the body. 6. Limbic functions: Ant nuclei of subjective feelings of personality, emotions and effect of a sensation. 7. Thalamus is also concerned with storage and recall of memory through activation of smaller portions of generalized thalamocortical pathway. 8. Medial dorsal and lateral dorsal nuclei project to cortical association areas and are concerned with language function. 9. Perception of visceral sensations esp. Pain.

Applied :- Thrombosis of thalamogeniculate artery produces thalamic syndrome characterized by. 1. Loss of fine sensation 2 Sensory ataxia 3. astereognosis. 4. Overreaction to painful stimuli 5. exaggeration of affect of a sensation and 6. abnormal movements.

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134 *Q. Describe The Function of Hypothalamus:

A) Behavioral Functions :

1. Regulation of emotional behavior – hypothalamus is part of limbic system and is responsible for effect as well as autonomic response associated with emotions. Stimulation of fear centre in preoptic area produces responses like tachycardia, sweating, cutaneous vasoconstriction and papillary dilatation. Rage responses is seen on stimulation of rage centre in lat. hypothalamus and periventricular areas. Stimulation of reward centre in ventromedial nucleus gives pleasantness while that of punishment centre in periaqueductal area produces unpleasantness. These areas are responsible for affect and provide motivation for learning. 2. Sexual behavior stimulation of areas in lateral hypothalamus along medial forebrain bundle increases sexual drive in animals. 3. Regulation of food intake : Lateral hypothalamus contains a feeding centre which remains continuously active and stimulates food intake, while the satiety centre in ventromedial nucleus is activated by rise in blood glucose following food intake. When activated, satiety centre inhibits feeding centre and stops food intake. 4. Regulation of water intake: There is a thirst centre situated in lat. hypothalamus posterolateral to feeding centre. It is stimulated by increased osmolarity of ECF, by intracellular dehydration and by Ang. II leading to increases in water intake. 5. Regulation of body temperature : The preoptic area of ant. Hypothalamus is stimulated by central and peripheral warmth receptors and brings about responses to promote heat loss from the body like cutaneous vasodilatation and sweating. Post hypothalamus is concerned with responses to cold like shivering, cut. vasoconstriction, piloerection etc. Thus hypothalamus acts as a thermostat.

B) Endocrine Function: - 6. Regulation of water excretion: supraoptic nuclei secrete antidiuretic hormone in response to increased osmolarity or decrease in ECF volume. ADH then acts on collecting ducts of kidneys and increases water reabsorption. Thus water excretion can be controlled in accordance with the needs of the body. 7. Control of ant pituitary hormones :- Various nuclei of hypothalamus like arcuate, ventromedial nuclei secrete various releasing and inhibiting hormones which reach the ant pituitary through hypophyseal portal vessels and modify its secretion. Such hormones include GHRH, GHIH, TRH, GNRH, PRH and PTH. 8. Regulation of milk ejection and uterine contractility :- The paraventricular nuclei secrete oxytocin during sucking, causing ejection of milk (neuroendocrine reflex) and during labor producing expulsion of fetus.

9. Role in stress :- Stress conditions like hemorrhage, trauma etc. Act on hypothalamus to releases CRH which, in turn, releases ACTH which brings about release of cortiso1. Suggestions: facebook.com/asifpatel.ggmc

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C) Vegetative Functions :- 10. Control of cardiovascular Function :- Hypothalamus control the vasomotor, cardioaccelerator and vagal centers in medulla. It also produces parasympathetic (ant hypo) and sympathetic (post hypo) effects on stimulation. 11. Control of gastronistestinal function: Like gastric acid secretion, motility etc. by its effects on vagal centre and on autonomic functions. 12. Circadian rhythm of secretion of CRH, ACTH and cortisol. Applied Physiology : Damage to ventromedial nucleus produces rage reaction and hyperplasia. Adiposogenital syndrome results from damage to satiety centre and adjacent area producing gonadotropin releasing hormone. *Q. Describe The Functions of Limbic System :

Limbic system is phylogenetically older, area of brain consisting of septal area, paraolfactory area, nuclei of thalamus, hypothalamus, amygadala, parts of basal ganglia and hippocampus, surrounded by a zone of limbic cortex made up of orbitofrontal cortex, subcallosal gyrus, cingulate gyrus, parahippocampal gyrus and uncus. Functions :-

1. Limbic system is responsible for emotional behavior :- Emotions are subjective feelings of fear, rage, joy anxiety etc. and they are associated with visceral changes like changes in heart rate, blood pressure, respiration etc. Stimulation of amygdala and preoptic area produces fear reaction (sweating, tachycardia, pupillary dilatation). While stimulation of periventricular areas and lat. hypothalamus causes rage reaction (hissing, growling, tail lifting). Rage reaction is a release phenomenon and normally held in check by neocortex, ventromedial nucleus and amygdala. Visceral responses to emotions are also mediated through hypothalamus. Limbic cortex acts as association area for behavioral functions. 2. Sexual behavior: Stimulation along medial forebrain bundle increases sexual activity in male animals while amygadloid nuclei have inhibitory effect on sexual behavior. In human beings neocortex has greater control on sexual activity.

3. Motivation (effect) : Limbic system determines the effect of a sensation, whether it is pleasant or unpleasant. Stimulation of Reward centres (along medial forebrain bundle and ventremedial nucleus) produces pleasant sensation and motivates the animal to perform same task (e.g. bar pressing) again and again. On the other hand punishment areas (per ventricular and periaqueductal regions) produce unpleasant sensation and make the animal avoid a particular task. Motivation is essential for learning. 4. Olfaction: Prepyriform and pyriform cortex, uncus, corticomedial portions of amygdala, hippocampus and orbitofrontal cortex are the parts of limbic system in which olfactory pathway terminates. These areas are concerned with conscious perception of odour, association of smell with other sensations and selection or rejection of food depending on past smell experience.

5. Functions of hippocampus: Learning and consolidation of memory : hippocampus decides the importance of sensory impulses and directs the brain to convert significant information into long term memories (consolidation). 6. Functions of amygda1a :- a) It receives signals from various areas of limbic cortex and neocortex and acts as window for perception of one’s position in the society. b) It is concerned with behavioral response appropriate to the occasion. c) Feeding response like chewing involuntary movements also. 7. Autonomic responses :- Stimulation of orbitofrontal cortex and parts of hypothalamus, amygdala and hippocampus produces autonomic changes like changes in heart rate, B.P., respiration, gastrointestinal activity etc. Suggestions: facebook.com/asifpatel.ggmc

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136 Besides above functions, hypothalamus which is a part of limbic system also performs other functions like regulation of food and water intake, regulation of ant pituitary hormones. Applied physiology :- Bilateral removal of amygdala and overlying cortex in animals produces Kluver Bucy syndrome characterized by placidity, fearlessness, hyperplasia, oral tendencies, visual amnesia (psychic blindness) and hypersexuality. Damage to hippocampus causes anterograde amnesia and inability to learn. *Q. Describe The Connection And Functions of Basal Ganglia :

Basal ganglia include caudate nucleus, putamen (neostriatum), globus pallidus, sub thalamic nucleus of Luys, substantia nigra, claustrum and red nucleus. Connections :-

A) Afferent fibers coming to basal ganglia :- 1) From motor cortex, premotor, supplementary motor area, prefrontal areas and sensory cortex (areas 4, 4s, 6, 8, 24, 3, 1, 2 etc) to caudate nucleus and putamen. These fibers release Acetyl choline. 2) From Thalamus (centromedian nu) to neostriatum 3. From Raphe nuclei of brain stem to neostriatum (serotoninergic fibers) 4. From motor cortex to substantia nigra. 5. From motor and premotor areas, vestibular nuclei and cerebellum (dentate) to red nucleus. B) Efferents :- Globus pallidus is major efferent pathway.

1. From globus pallidus to VA and VL nuclei of thalamus. 2. From globus pallidus to segmental nuclei and reticular formation. 3. From substantive nigra to spinal cord. 4. sub thalamic nigra to thalamus. 6. Subthalamic nucleus to thalamus. 7. From red nucleus to VA, VL nuclei of thalamus (rubrospinal).

C) Interconnections :- 1. Neostriatum to substantia nigra (GABA ergic fibers) 2. Substantia nigra to Neostriatum (Dopaminergic fibers). 3. Neostriatum to globus pallidus (GABAergic) 4 Ext. Globus pallidus is reciprocally connected with subthalamic nucleus. 5. Substantia nigra reciprocally connected with sub thalamic nucleus . 6. Substantia nigra to red nucleus. Function of Basal ganglia :-

1) Control of voluntary movements : The putamen circuit (premotor, supplementary motor, sensory cortexputamen- internal globus pallidus – VA and VL nuclei of thalamus – primary motor cortex) works with motor cortex and corticospinal tracts and controls complex, subconscious, learned patterns of movements like writing, driving a vehicle, working skills, games skills etc.

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2. The caudate circuit (Association areas of Frontal, parietal and temporal lobes- caudate nu- int globus pallidus - VA, VL nuclei - prefrontal, premotor and supplementary motor areas) is concerned with planning the timing and sequencing of complex motor patterns in responses to thought process (Cognitive movements.).

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3. Basal ganglia are concerned with initiation and control of gross voluntary movements of the body like walking, sitting etc. They are the highest controlling centres for voluntary activities in lower animals. 4. Basal ganglia are also responsible for automatic and associated movements like facial expression, swinging of arms while walking etc. 5. Globus pallidus and subthalamic nucleus control the axial and girdle muscles (proximal fixation) so that discrete movements can be carried out at distal joints by pyramidal tracts. 6. Basal ganglia, especially, caudate nucleus, have inhibitory effect on muscle tone throughout the body (by stimulating bulbar inhibitory area) and also decreases sensitivity of stretch reflex. 7. They also control posture by sending impulses through extrapyramidal tracts 8. They prevent occurrence of abnormal movement like tremors at rest. 9. Red nucleus gives rise to robrospinal tract which is functionally similar to pyramidal tract and controls discrete movements. In animals red nucleus forms centre for righting reflexes. Applied aspect : Depletion of dopamine in nigrostriatal pathway produces Parkinson’s disease characterized by lead pipe rigidity, poverty of movements, mask like face, resting tremors and shuffling gait. *Q. Define Sleep. Describe the Types of Sleep & Their Mechanisms:-

Def :- Sleep is a naturally occurring reversible state of unconsciousness from which a person can be aroused by appropriate sensory stimuli and which is characterized by reduced sensitivity to changes in the environment.

There are 2 types sleep : 1. Slow wave sleep or NREM sleep. 2. REM sleep or Paradoxical sleep : when a person falls asleep, he enters NREM sleep which lasts for 65 to 70 min followed by REM sleep lasting for 30 min. Then NREM sleep occurs again and the events are repeated in a cyclical manner (sleep cycle), each cycle lasting for 90 to 100 min. Non Rapid Eye Movement (NREM) sleep of slow wave sleep or Deep Sleep: Features: 1) Deep restful sleep :- Dreams may occur, but are not consolidated, hence are not remembered. 2. There is decrease in heart rate, cardiac output, vasomotor tone and blood pressure. 3. Respiration becomes deep and regular. Respiratory rate decreases. Sometimes Cheyne stokes respiration may be seen. 4. Basal Metabolic Rate falls by 10 to 15 %, Body temperature is reduced. 5. There is decrease in muscle tone and muscles are relaxed. Reflexes are sluggish. 6. Babinski sign is present7. Threshold for sensory stimuli is raised and the person is less aware of changes in environment. 8. There is decrease in salivary and lacrimal secretion. 9. Motility of gastrointestinal tract is increased due to parasympathetic effects 10. There is relaxation of eyelid levator and drooping of eyelids. 11. Papillary constriction. 12. Urine formation is reduced. 13. EEG Changes: - There are 4 stages of deep sleep according to EEG changes. Stages I : In which as the person starts dozing, beta waves are replaced by alpha waves which are replaced by theta waves(transition from wakefulness to sleep). Suggestions: facebook.com/asifpatel.ggmc

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138 Stage II : characterized by short spindle shaped called 'Sleep spindles' and K complex. Stage III : (actual deep sleep)high amplitude theta waves and few delta waves

Stage IV : Theta waves totally replaced by delta waves indicating synchronization of cortical activity.

Mechanism of NREM sleep. It results from active inhibition of neurons of reticular activating system by the raphe nuclei. These nuclei are situated in midline which inhibits RAS. (According to passive theory sleep is due to fatigue of RAS neurons.)

Rapid Eye Movement (REM) Sleep of Paradoxical Sleep or Desynchronized sleep Features :- 1. This sleep is more intense (deeper) than NREM sleep. 2. There are rapid roving movements of the eyeball which may be due to a) dreams b)activation of vestibular nuclei c) PGI spikes 3. Dreams occur in this type of sleep and they are remembered. 4. There is extreme inhibition of muscle tone in the body due to increased activity of inhibitory portion of bulbar reticular formation. It prevents motor responses to dreams. 5. Threshold for arousal from sleep is raised and if a person is aroused, he is highly irritable. 6. Heart rate and respiration may become irregular (due to dreams?). 7. May be associated with grinding of teeth, penile erection and somnambulism. 8. Brain is highly active and brain metabolism is increased. 9. Large phasic potentials are observed arising from Pons and passing to lateral geniculate body and occipital cortex (PGO spikes). 10. EEG shows high frequency low voltage irregular beta waves as seen in alert wakeful person. Thus the EEG shows a desynchronized pattern even though the person is in greater depth of sleep. Hence called Paradoxical sleep. Mechanism of REM sleep: It is caused by discharge from noradrenergic neurons of locus ceruleus situated in pons. Activity of these neurons causes desynchronization of cortical activity via a pathway that bypasses RAS. Hence the person is asleep but shows desynchronized pattern in EEG. *Q. Describe The Function of Ascending Reticular Activating System:-

ARAS is a complex multineuronal and mutisynaptic pathway arising from reticular formation of lower, brainstem, mesencephalon and thalamus and projects diffusely to the entire cerebral cortex.

Projections from mesencephalic portion of RAS pass to cerebral cortex Via 2 pathway : 1. One pathway originates from mesencephalic portion of reticular formation and passes upward through the intralaminar, midline and reticular nuclei of thalamus and then through the diffuse or generalized thalamus cortical pathways to entire cerebral cortex. 2. A second pathway by passes thalamus and instead goes through hypothalamus and sub thalamus:

Afferents to ARAS come from :- 1. Collaterals from all ascending sensory tracts, those carrying general sensations like touch, pain, proprioception and also from those carrying special sensations like auditory and visual pathway. 2. Fibers form cerebral cortex:- Asp motor cortex, frontal lobe and superior temporal gyrus also end in mesencephalic portion of RAS.

Functions : 1. Alertness and wakefulness :- This system is responsible for wakefulness and alertness of the individual by bringing about generalized activation of all portions of cerebral cortex. Wakefulness is defined as activity in the brain directed into appropriate channels to give a person a sense of conscious awareness. 2. Arousal : Stimulation of RAS in sleeping animals produces arousal response and desynchronization of EEG. Activation of ARAS can be brought about by a) Strong sensory stimuli like vigorous shaking of the body or loud sound. b) by impulses coming from motor cortex (therefore a person keeps on moving about if he wants to avoid sleep) and c) by epinephrine. 3. Perception:- Activation of RAS heightens the level of perception of a sensation (reduces threshold for sensation) and helps in initiation of appropriate responses. Suggestions: facebook.com/asifpatel.ggmc

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4. Reaction Time :- ARAS maintains the normal reaction time.5. Sleep : Inactivation of RAS produces sleep. Sleep results from active inhibition of RAS by serotoninergic neurons situated in raphe nuclei of brain stem. 6. Sleep wakefulness cycle : According to passive theory of sleep, once ARAS is activated its activity is maintained for long time in a positive feedback manner. However after prolonged wakefulness (15 to 16 hours) excitability of RAS neurons decreases, positive feedback cycles are cut off and the person goes to sleep. During sleep, the ARAS neurons recover and on activation produce wakefulness. Thus sleep wakefulness cycle continues.

7. Stimulation of : Cerebral cortex and this might be the mechanism for directing our attention to specific mental activity and for recall of memories. 8. Emergency response :- In emergency stressful conditions, releases of epinephrine activates RAS which then facilitates Fight or flight response. 9. RAS helps in establishment of conditioned reflexes. Applied aspects:- Tumors, trauma or thrombosis involving RAS cause loss of consciousness and coma. Depression of synaptic transmission in RAS in the principle of an aesthesia. *Q. Define And Classify Memory. What Are Mechanisms for Storage of Memory?. Def: Memory is the ability to store the information and to recall it when needed.

Types of memories : 1) Immediate (sensory) memory: It is the ability to recall events of the moment. It is the memory of facts, numbers and words etc. lasting for few seconds to few minutes e.g. digits of telephone no. after looking into the directory. This information is instantly available. During this period information can be scanned and analyzed and if found important can be subjected to consolidation. Mechanisms :- a) Reverberating circuit theory :- Sensory impulses coming to cortex set up reverberating oscillatory circuits between the neurons of the cortex and thus information is available as long as reverberations continue. b) Post Tetanic Potentiation theory : Passage of repeated impulses through synaptic circuits facilitates these circuits due to accumulation of more Ca ions in presynaptic terminals and prolonged release of neurotransmitter.

2. Short Tem Memory:- Information is retained from few minutes to hours, days and few weeks. Recall is fairly rapid. This type of memory is lost by blow on head, anesthesia or electric shock. Mechanism :- It results from temporary physical and chemical changes in synapses like Presynaptic facilitation mechanism. In this mechanism, facilitator terminal ends presynaptically on a sensory terminal causing formation of cyclic AMP which blocks K channels. This prolongs the action potential in sensory terminal and increases releases of synaptic transmitter. Thus such facilitated circuits are formed which can be excited for recall of information. 3. Long term memory:- Which can be recalled after weeks, months and years. Information has to searched through the memory stores and may take some time to recall : It is not lost by concussion or electric shock.

Mechanism: Storage of this type of memory results from anatomical changes in synapse like a) Increase in the no. of release sites. b) increase in the number of transmitter vesicles in presynaptic terminals. c) Increase in no. of presynaptic terminals. d) Change in the number of neurons in the circuit. These changes keep such synaptic circuits permanently facilitated. Hence called ‘Memory trace’ or Memory engram. Storage of memory is associated with increased RNA synthesis. Consolidation of Memory:- Is the process of fixation of immediate, into short-term and then into long term memories. It takes 10 minutes to 1 hour and results from rehearsal of information again and again. It is brought about by hippocampus (cal neurons) which consolidates and encodes the memory. On the other hands, tha1amus helps to recall the memory through smaller portions of diffuse thalamocortical system. Suggestions: facebook.com/asifpatel.ggmc

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140 Applied physiology:- Damage to hippocampus causes anterograde amnesia and that to thalamus causes retrograde amnesia. *Q. Describe The Carniosacral Outflow of Autonomic Nervous System And Its Functions :

The efferent fibers of parasympathetic system arise from brainstem and sacral portions of spinal cord. Hence this system is called craniosacral outflow.

A) Cranial Outflow : 1. Through oculomotor nerve: Fibers arising from Edinger westphal nucleus are relayed in ciliary ganglion and supply ciliary muscle and constrictor papillae. 2. Through Facial nerve :- Fibers arising from superior salivary nucleus are relayed a) through sphenopalatine ganglion to lacrimal apparatus and b) through submandibular and sub lingual gland. These are secretomotor and vasodilator fibers. 3. Through Glossopharyngal nerves : Arising from inferior salivary nucleus are relayed through otic ganglion to parotid glands. 4. Through Vagus:- Vagus contains 75% of parasympathetic fibers. Postganglionic fibers which arise from dorsal motor nucleus are long and extend all the way to organ of supply where they and on intragang1onic cells. Postganglionic fibers arising from these cells supply a)Heart which is inhibited and coronaries(dilatation). b) Lungs and dilator fibers to bronchial muscle c) Gastrointestinal tract smooth muscle from oesophaus to proximal half of transverse colon and vasodilator and secretary fibers to glands d) Secretomotor fibers to pancreas and liver e) Gall bladder for contraction of smooth muscle. B) Sacral Outflow :- Arises from S2 S3 and S4 segments of spinal cord and passing through pelvic nerve supplies distal colon and urinary bladder causing contraction of smooth muscle and relaxation of sphincters. It also supplies vasodilator fibers to external genitals.

Functions of Parasympathetic system :- 1. Parasymp system is mainly concerned with anabolic activities necessary for conservation of body energy and for resting of vital organs. 2. It has inhibitory control over heart and reduces heart rate, force of contraction, excitability and conductivity.

3. It promotes digestion and absorption by increasing gastrointestinal secretions and motility emptying of rectum by defecation reflex and that of urinary bladder by micturition reflex. 5. It brings about parasympathetic reflexes of the eye like papillary light reflex which controls entry of light into eye and accommodation reflex to focus near objects. 6. It helps in initiation of male sexual act by causing erection of penis resulting from parasympathetic vasodilatation. 7. It also stimulates secretion of hormone like insulin, gastrin etc. The neurotransmitter released from parasympathetic ending is Acetyl choline which is responsible for all these actions. Applied aspects:- Congenital absence of parasympathetic ganglia in a segment of colon causes Hirschoprung’s disease. *Q. Describe Various Waves In Electroencephalogram, Their Origin And Significance:-

Def:- EEG is a record of spontaneous electrical activity taking place in superficial layers of cerebral cortex obtained by placing electrodes of the surface of head. It is usually recorded by placing 2 electrodes on specified areas of scalp (Bipolar BEG). Waves of EEG :- 1. Alpha waves: They have a frequency of 8 to 13 per second and their voltage is around 50 microvo1ts. They are recorded mainly in occipital and parietal regions of the scalp. The alpha waves are recorded in adult humans at rest but who are awake with eyes closed and mentally relaxed :- (resting state of cerebration). Suggestions: facebook.com/asifpatel.ggmc

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They are also seen second stage of NREM Sleep it the form of spindle shaped bursts called sleep Spindles :They disappear on opening the eyes or following sensory stimulation or specific mental activity and are replaced by high frequency low voltage waves. This is called Alpha block or desynchronization or arousal response :

during mental tension.

Beta waves :- They are high frequency low voltage waves. Voltage of 5 to 10 micro volts. They are mainly recorded from frontal and parietal regions. They are observed in alert wakeful state, in REM Sleep and

Theta waves :- Are large regular waves with a frequency of 4 to 7 per second and voltage of 50 to 70 micro volts. They are recorded mainly from parietal and temporal regions. They are observed normally in children and during sleep and in adults following disappointment of frustration.

Delta waves :- Are low frequency (0.5 to 3.5 per sec) high voltage (up to 200 micro volts) waves seen in various conditions like deep sleep, infancy, hypoxia, coma and in brain tumors. Origin of EEG waves:- Superficial layers of cerebral cortex mainly contain dendrites. Hence EEG is not the results of summation of action potentials. They are due to the local current flows between the dendrites and soma of cortical neurons as a results of formation of fluctuation dipoles which occur due to arrival of impulses on fluctuating dipoles which occur due to arrival of impulses on dendrites from RAS. Alpha waves are due to spontaneous activity in generalized thalamocortical system which from asynchronous activity of cortical neurons. Theta waves originate from hippocampus. Delta waves are due intrinsic synchronization activity of cortical neurons when removed from the influence of thalamus or ARAS. Importance of EEG :- 1. Useful in diagnosis of type of epilepsy and location of epileptic focus (Grand mal epilepsy high voltage discharge, petit mal epilepsy- dome and spike pattern 2. Diagnosis and localization of brain tumors’ (delta waves). 3. Localization of subdural hem atoms 4. Diagnosis of psychiatric disorders (theta wave). 5. To confirm brain death so that organs can be removed for transplantation. *Q. Describe Thoraculumbar Outflow And its Function:

Efferent fibers belonging to sympathetic system arise from thoracic and lumbar segments (T1 to L3) of spinal cord, hence this system is called thoracolumbar outflow. Here the preganglionic fibers end in either paravertebral or collateral ganglia or postganglionic fibers supply the organs.

1. Outflow to head neck:- arises from T1, T2 segments. And relayed through superior cervical ganglion to ciliary body and dilatory papillae of eye and vasoconstrictor fibers to lachrymal parotid, sublingual and submandibular glands. 2. Outflow to heart arises from T1 to T5 segments and relayed through sup, middle and inferior cervical ganglia and cardiac nerves to the heart. It has excitatory effect on heart. 3. To bronchi and pulmonary vessels through upper thoracic sympathetic constriction of pulmonary Vessels. 4. To abdominal viscera : a) Stomach and small intestine :- Fibers arising from T5 to T9 are relayed through celiac ganglion causing decrease in tone and motility, constriction to sphincters and vasoconstriction of stomach and intestine. They also supply liver (release of glucose) and gall bladder (relaxation) b) Colon, rectum and urinary bladder: - Fibers arising from L1 to L3 and Suggestions: facebook.com/asifpatel.ggmc

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142 relayed through inf. mesenteric ganglion supply these parts causing relaxation of smooth muscle and vasoconstriction, c) Kidneys and ureter get their sympathetic supply from T10 to T12 segments relayed through sup. mesenteric ganglion (vasoconstriction and increased peristalsis of ureter). d) Adrenal medulla : receives. Directly preganglionic fivers arising from T10 to T12: e) Uterus and male genitals from L1 to L3 through long preganglionic and short adrenergic neurons in them. They bring about emission and ejaculation in males. 5. At different levels of ps cord, postganglionic fibers arising from paraverterbral ganglia pass through gray ramus and join spinal nerves to supply sweat glands (cholinergic), cutaneous blood vessels and erector pilorum muscles.

Function of sympathetic system :- 1) Control of Cardiovascular function: sympathetic stimulation causes increases in heart rate, force of contraction, excitability and conductivity of myocardium. It also causes constriction of peripheral vessels. It thus control cardiac output, blood pressure and blood flow to the tissues through various cardiovascular reflexes normally and also during exercise. 2) Response to emergency situations:- There is mass activation of sympathetic system in emergency conditions like shock or encounter with enemy. In the latter condition it helps in fight or flight reaction. 3. Regulation of body temperature by exerting control over cutaneous vessels, sweat glands, piloerecetor muscle and by releasing adrenaline which is concerned with chemical thermo genesis: 4. Helps in maintaining blood glucose by releasing glucose from live. 5. It brings about activation of RAS by releasing adrenaline. 6. Responsible for emission and ejaculation of male sexual act. 7. Responsible for visceral expressions of emotions like fear, rage etc. 8. Ciliospinal reflex of pupil. Neurotransmitters: - Most postganglionic symp. endings releases noradrenalin which acts mainly on alpha receptors stimulation of adrenal medulla releases adrenaline which acts, on alpha as well as beta receptors. However sympathetic fibers ending on sweat glands and skeletal muscle, blood vessels release Acetyl choline. Presynaptic Inhibition:-

Def :- It is a type of synaptic inhibition in which there is inhibition of presynaptic terminal leading to suppression of synaptic transmission. Mechanism:- In this type of inhibition, there is a presynaptic terminal A which terminates on another presynaptic terminal B, which in turn terminates on a postsynaptic neuron. When stimulated, presynaptic terminal A release a transmitter like GABA on presynaptic terminal B. This transmitter either blocks voltage gated Ca channels inhibits opening of Na channels in presynaptic terminal B. Therefore there is decrease in amplitude of action potential and reduced Ca entry in this terminal on arrival of action potential. Hence less quantity of neurotransmitter is released into synaptic cleft and excitation of postsynaptic neuron is reduced. Thus synaptic transmission is inhibited before the impulse arrives at the synapse. Presynaptic inhibition requires many milliseconds to develop, but once it occurs, it may persist for minutes or hours. Significance : This type of inhibition is seen is in most sensory pathways in which adjacent nerve fibers inhibit each other (lateral inhibition) so that sensation becomes very sharp. It also forms the basis for Gate control theory of pain sensation at the substantia gelatinosa and use of counterirritants. Knee Jerk:

It is the reflex contraction of quadriceps femoris muscle causing extension of knee when the patellar tendon is tapped with a percussion hammer. Pathway :- It is a dynamic, monosynaptic Suggestions: facebook.com/asifpatel.ggmc GGMC MUMBAI

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stretch reflex and its centre is situated in L2, L3, L4 segments of spinal cord. When patellar tendon is tapped muscle spindles in quadriceps are stretched suddenly. The annulospiral endings are stimulated and afferent impulses pass through IC fibers in to spinal cord where they directly end on motor neurons supplying quadriceps and stimulates them. Therefore the muscle contracts. The reflex can be reinforced by a simultaneous strong voluntary activity such as interlocking of fingers or clenching of teeth (Jendrassik’s maneuver). Clinical Significance :- In upper motor neuron lesion involving large areas of motor cortex (hemiplegia) the knee jerk is exaggerated due to facilitation of gamma motor neurons by pontine reticular facilitatory area. There may also be patellar clonus. In LMN Lesions e.g. Poliomyelitis, knee jerk is lost due to interruption reflex arc. In cerebellar disorders, knee jerk becomes pendular due to hypotonia and loss of damping function. In conditions like tabes dorsalis or peripheral neuritis sensory part of reflex arc is broken and knee jerk is lost. It thus helps to locate the site of lesion. Golgi Tendon Organ :

Structure :- It is a sensory receptor made up of a group of knob like nerve ending situated in

tendon fascicles which are formed by joining together of 10-15 muscle fibers. It is situated in series with muscle fiber.

Functions : 1. It regulates tension in muscle fibers: when the muscle fibers contract or when the muscle is passively stretched the tension in tendon fascicles increases and Golgi tendon organs are stimulated. Therefore these organs detect tension in the muscle. Impulses arising from tendon organs pass through I b fibers enter spinal cord through dorsal root and end on inhibitory interneuron which when terminates on motor neurons supplying that muscle. Therefore when muscle tension increases, these receptors are stimulated and produce reflex inhibition of that muscle. This is known as Inverse Stretch reflex or autogenic inhibition and prevents excess rise in muscle tension. 2. When muscle tension rises extremely, it causes instantaneous relaxation of muscle. This is called lengthening reaction and prevents rupture or avulsion of muscle. 3. It equalizes contraction force in all muscle fibers. 4. It sends afferents through dorsal column pathway for conscious proprioception and through spinocerebellar pathway to the cerebellum informing it about muscle tension which is essential for control of voluntary movements. Afferents arising from these organs shows 2 types of responses, dynamic responses informing rate of change of tension and a static response indicating a sustained increase in tension. Romberg’s Sign : Named after Moritz Romberg, a German neurologist. It is a sign of sensory ataxia. Sensory ataxia means lack of co-ordination of movements due to absence of sensory inputs. Test: It is detected by asking the patient to stand erect with feet close together. First he is asked to keep both eyes open and the degree of swaying is noted. He is then asked to close the eyes and observed. If the patient begins to sway on closing the eyes (and may sometimes fall), it is called Romberg’s Sign.

Explanation: - In a patient with sensory ataxia, there is loss of proprioceptive impulses (position sense) because of damage to sensory nerve fibers or dorsal column, but he is able to maintain his posture without swaying as long as eyes are open because of visual impulses. When the eyes are Suggestions: facebook.com/asifpatel.ggmc

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144 closed, visual clues are lost and patient is unable to maintain posture. Hence he starts swaying sensory ataxia is seen in peripheral neuritis, leprosy, tabes dorsalis etc. In cerebellar ataxia or labyrinthine ataxia (motor ataxia) there are no aggravations of swaying on closure of eyes, because in these conditions, the motor component of co-ordinations is affected and therefore closure of eyes does not make any difference. Thus Romberg’s sign helps to differentiate sensory ataxia from

motor ataxia.

*Q. Classification of Nerve Fibers : I. General Classification:

(Erlanger and Gasser’s) Depending upon diameter of nerve fibers. Class

Diameter

-----

In microns

A alpha

A beta 6-12 A gamma A delta B

12-20 3-6

2-5

Less than 3

0.4-1.2

(dorsal root)

Velocity

of impulses 70-120 m/s

30-70 m/m

15-30 m/s

Number

---------------

Somatic motor, proprioception

Afferents for touch pressure

12-30 m/s 3-10 m/s

0.5-2 m/s

II. Numerical Classification :

Function

Efferent’s to muscle spindle

Pain, temp, touch afferents

Autonomic preganglionic

Slow pain, symp afferents.

Origin

Group I a

Annulospinal endings

Group II

Flower spray endings touch receptors

Group IV

Burning pain, itch.

Group I b Group III

Golgi tendon organ

Pricking pain, crude touch, temp.

Other Classifications: III. 1. Afferent fibers carrying impulses towards nervous system. 2. Efferent fibers – away from N.S. IV. 1. Somatic fibers carrying somatic impulses. 2. Visceral fibers carrying visceral impulses. V.1. Militated fibers having are more susceptible to pressure and hypoxia and resistant to local anesthetics while type C fibers are easily blocked by local anesthetics 2. The type of impulses that should be carried fast eg. Spinocerebellar (proprioception) or corticospinal (motor impulses) are transmitted through A alpha fibers which have maximum velocity.

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*Q. Hemisection of SP. Cord (Brown Sequard Syndrome)

Means damage to one lateral half of spinal cord. May occur due to gunshot injuries or accidents or tumors. Immediately after hemisection, patient goes into a stage of spinal shock in which there is unconsciousness, flaccidity and are flexia. After recovery following effects are seen. A) Below the level of lesion :- 1. Sensory changes: On the same side, there is loss of epicritic touch (topognosis, tactile discrimination,) vibration, position and kinesthetic (proproception) sensations due to damage to dorsal column pathway. Crude (protopathic) touch, pain and temp not affected. On the opposite side, crude touch, temp, tickle, itch and pain are lost due to damage to spin thalamic tracts which cross at spinal level.

2. Motor : On same side, there is upper motor neuron type of paralysis characterized by clasp knife spasticity, exaggerated deep reflexes, loss of sup reflexes Babinski sign and loss of voluntary movements. These effects are due to damage to crossed pyramidal tracts. On the opposite side, some muscles may show UMN paralysis due to damage to uncrossed pyramidal tract. 3. Vasomotor Changes : - Transient loss of vasomotor tone leading to vasodilatations. B) Change at the level of lesion : 1. Sensory changes : On same side, there is loss of all sensations in that dermatome due damage to dorsal root fibers entering the cord. 2. Motor changes: - There is Suggestions: facebook.com/asifpatel.ggmc

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146 lower motor Neuron type of paralysis characterized by flaccidity, loss of sup and deep reflexes, wasting of muscles etc. Due to damage to spinal motor neurons. 3. There is permanent loss of vasomotor tone in that segment. C) Above the level of lesion, there may be a band, of hyperesthesia due to irritation of damaged fibers. Babinski Sign :

Named after Joseph Babinski, a French neurologist. It is an abnormal pathological reflex that appears when there is damage to corticospinal (pyramidal) tracts.

Elicitation: - When the skin of the sole of foot is stroked along its lateral border with a blunt object, there is plantar flexion of great toe and other toes in a normal person. This is called plantar reflex. It is a superficial reflex and has a root value of L5 S1 S2. If there is damage to pyramidal tracts, same procedure causes dorsiflexion of Great tone and fanning out of other toes : This is called Babinski Sign sometimes there may be flexion at knee and hip joints also. Explanation: - Normally intact corticospinal tract produces plantar flexion of toes on stimulation of sole so that the foot and toes take a firm grip on the ground and help in thrusting the body forwards for locomotion. When it is damaged, the primitive motor (extra pyramidal) system is functioning and it produces withdrawal reflex. Which is protective is nature. This withdrawal reflex is manifested as dorsiflexion of great toe and fanning out of other tones. Thus Babinski sign is a release phenomenon because normally it is suppressed by intact corticospinal tract. Babinski sign is also seen in conditions like deep sleep, coma and in infants (before myelination), in which the influence of pyramidal tract on spinal neurons is removed. *Q. Pain Control (Analgesic) System in Body

Consists of natural mechanism of inhibition of pain in the body. It includes :

1. Descending inhibitory pathways: - a) Periventricular nuclei of hypothalamus and periaqueductal area- Neurons of these areas gives rise to fibers which release enkephalins on raphe nuclei. b) Raphe Magnus nucleus situated in midline in lower Pons and upper medulla. It's serotonergic fibers extend to dorsal horns of spinal cord. c) Pain inhibitory complex in dorsal horn of spinal cord-

Raphe neurons end on local neurons of sp. cord which secrete enkephalin, which, in turn, cause presynaptic inhibition of A delta and also dorsal root C fibers into sp. cord inhibited which persists for few minutes to few hours. This natural analgesic system is stimulated by various factors such as 1) Endogenous analgesic substances like beta endorphin, met and leu enkephalin etc. which are secreted by anterior pituitary adrenal medulla and by cells of GIT. When they combine with receptors on periaqueductal area, this area is stimulated and impulse pass-through descending pathway inhibiting entry of pain signals in sp. cord. 2) Collaterals arising from ascending spinothalamic tracts can also stimulate raphe nuclei or PAG area. 3 Stimulation of large diameter touch fibers decreases transmission of pain impulses into sp. cord by causing lateral (presynaptic) inhibition of pain fibers- Gate control theory of pain. Suggestions: facebook.com/asifpatel.ggmc

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147 Visceral Pain:-

Is the pain arising from abdominal and thoracic viscera. Receptors in viscera are mainly pain receptors and these too are few in number. Therefore pain is produced only when a large portion of viscera is involved.

Visceral pain receptors are stimulated by various stimulation as 1. Ischemia leading to production of bradykinin. 2. Spasm of smooth muscle of a hollow viscus like stomach intestine etc. 3. Overdistension of a viscus. 4. Inflammation e.g. appendicitis. 5. Chemicals like gastric acid released into peritoneal cavity (perforation). Transmission :- Visceral pain is mainly transmitted through sympathetic afferent fibers which are small C type fibers and transmit burning type of pain. Ultimately it passes through paleospinothalmic pathway to reticular formation and thalamus where it is perceived. Visceral pain is poorly localized and is usually referred to the surface of the body, at a site distant from viscera, but which is developed from same embryonic segment e.g. cardiac pain referred to medial aspect is associated with other effects like nausea, vomiting, sweating, fall in BP etc. It may also initiate reflex contraction of adjacent skeletal muscle producing guarding. Pain arising from hollow viscous is colicky in nature. Withdrawal Reflex:-

It is the reflex contraction of flexor muscles of a limb when a strong painful stimulus is applied to it, so that the limb is withdrawn from the stimulus. It is a protective reflex and essential for survival. : Application of painful stimulus excites pain receptors and afferent are carried into sp. Cord though dorsal roots fibers. These fibers and on series of interneuron’s (more than 3 to 4) which ultimately end on motor neurons supplying flexor muscles of the liable causing their contraction. Thus it is a polysynaptic reflex integrated at sp. cord level. Other features of withdrawal reflex :- 1) Irradiation: - As the strength of painful stimulus increases, more and more flexor muscle contract producing greater and wider response. This is due to irradiation of impulses in sp. cord. 2) Crossed extensor reflex:- A strong painful stimulus also causes extension of opposite limb. It is due to spread of impulse to the other side of sp. cord and reciprocal connections between the two sides to the cord. 3) After discharge:- A) Strong withdrawal reflex persist for few seconds even after removal of painful stimulus due to after discharge or neurons in polysynaptic circuits. 4) Local sign :- Response in withdrawal reflex also depends upon site of stimulus, if stimulus is applied on medial aspect of arm, then there is abduction in addition to flexion. Reciprocal Inhibition:-

When stretch reflex is elicited in one group of muscles, there is simultaneous inhibition of antagonist muscle. Similarly whenever there is contraction of agonist muscle, there simultaneous relaxation of antagonists. This is called Reciprocal inhibition. Inhibition of antagonist muscle permits movements to underlying this mechanism is called. Reciprocal inhibition. Afferents arising from muscle spindles of agonist muscles enter sp. cord and end directly on motor neurons. They also give a collateral to an inhibition interneuron called Golgi Bottle neuron which ends on motoneuron supplying antagonist muscle. Therefore when agonist muscle contracts, Golgi bottle neurons is stimulated which releases inhibitory transmitter and produces IPSPS on antagonist motor neurons causing its relaxation. Suggestions: facebook.com/asifpatel.ggmc

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148 Similar reciprocal innervations exists between two side of sp.cord and between forelimbs and hind limbs and forms the basis of some of locomotion reflexes. Reciprocal inhibition is thus a function of sp-cord and can be demonstrated in spinal preparation of frog. *Q. Nystagmus :-

Nystagmus is involuntary, jerky, to and fro movements of the eyeballs. The movements. may be horizontal, vertical or rotatory. There are 2 main types of nystagmus. 1) Vestibular nystagmus 2) Cerebellar nystagmus. Vestibular nystagmus :- Results from stimulation of semicircular canals and is seen during (rotational) and after (post rotational) rotation of the body. It is a reflex that maintains visual fixation on stationary points while the body rotates (Vestibulo-ocular reflex). Nystagmus has two components; a slow component which occurs in a direction opposite to rotations and a fast component in the direction of rotation. The slow component is initiated in semicircular canals and the impulses pass through vestibular nerve to vestibular nuclei and then through medial longitudinal fasciculus to the nuclei of cranial nerves supplying ocular muscles. It can be elicited as a part of vestibular Function Tests by syringing the ears with cold water (caloric test) or rotating a person in Barany’s chair.

Applied aspects: - Nystagmus can occur as occupational hazard in engine drivers Or miners Cerebellar nystagmus :- is seen in cerebellar diseases due to failure of damping function of cerebellum causing the eyeball movt to overshoot the point of intention followed by overcorrection. *Q. Blood Brain Barrier:-

It is the hypothetical barrier that exists between blood and interstitial fluid of the brain. Similarly a blood CSF barrier exists between blood and CSF.

Permeability: - Substance like water, Co2 and O2 cross BBB rapidly because of their smaller molecular size and/or lipid solubility. Glucose crosses the barrier slowly. Electrolytes like Na, K, H, C1 and HCO3 also cross the barrier slowly. Plasma proteins, most hormones and other large mol wt organic substances cannot pass through the barrier. Cause of the barrier BBB is attributed to 2 factors. 1. There are tight junctions between adjacent endothelial cells of cerebral capillaries and there are not slit pores. Therefore permeability of theses capillaries is less. 2. Foot processes of astrocytes completely surround these capillaries. Exception:- BBB is absent in some parts of brain such as area postrema and parts of hypothalamus which contain receptors for osmolarity and blood glucose. Function of BBB: - 1. Maintains constancy of milieu interior of neurons. 2. Protects brain from endogenous and exogenous toxins. 3. Prevents escape of neurotransmitters into circulation.

Clinical Significance:- 1. Drugs like sulfa and erythromycin can cross the barrier while penicillin cannot. 2. In treatment of Parkinsonism, L dopa is used which can cross BBB. 3. Kernicterus can occur in infants because BBB is absent. *Q. Thalamic Syndrome:

Results from thrombosis of thalamogeniculate branch of posterior cerebral artery causing damage to postroventral portion of thalamus. Features :- 1. Loss of almost all sensations from opposite side of body due to damage to relay nuclei of thalamus. However, some crude sensations Suggestions: facebook.com/asifpatel.ggmc GGMC MUMBAI

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like crude touch temp etc. May be present. There is astereognosis, that is inability to recognize common objects by their size, shape, weight, texture etc. 2. There is increases sensitivity for pain stimuli, even minor stimuli of other type can cause severe unpleasant pain sometimes pain occurs spontaneously. 3. There is sensory ataxia i.e. lack of precise control of movements and Incoordination. It results from loss of position sense and kinesthetic sense arising from peripheral parts of body which are relayed through thalamus. 4. There may be abnormal involuntary movements such as intentional tremor and choreoathetosis. Intension tremor is due to damage to cerebello- thalamo cortical pathway. 5. Affect of all sensations is exaggerated i.e. there is increased emotional response to stimuli. This is especially true of pain sensation which becomes extremely unpleasant. There may be emotional disturbances. These effects are due to facilitation of medial nuclei of thalamus which remain intact. Function of Prefrontal Lobes:-

Prefrontal lobe is the portion of frontal lobe of cerebrum situated in front of promotor area, and includes areas 9, 10, 11, 12, 13, 14 and 24.

Functions: - A) Higher functions: 1. It prevents distraction and keeps mental activity directed towards goals. 2. Simultaneous storage of many types of information (memory) and its recall for various intellectual functions. 3. It is concerned with elaboration of thoughts, that is depth in through process. 4. It has predictive function which helps in planning sequence of future events. 5. It regulates moral and social behavior appropriate to the occasion. 6. It is concerned with delaying responses to a stimulus and considering consequences of an action before the action is preformed. 7. Higher intellectual functions like judgment, medical diagnosis, solving mathematical problems etc. 8. Stimulation of area 13 produces autonomic responses like changes in heart rate, BP, respiration and gastrointestinal motility. It is therefore responsible and for autonomic expressions of emotions. 9. It is concerned with effect of pain sensation and prefrontal lobotomy helps the patient to neglect intractable pain. B) Motor functions:- It is concerned with planning and programming of complex voluntary movements in association with caudate circuit. Applied aspects :- Damage to prefrontal lobes produces easy distractibility, flight of ideas, lack of self restraint, in appropriate social and moral behavior, disturbance or disorientation etc. Emotions:-

Emotions are the subjective feeling like fear, rage, joy etc. Associated with visceromotor changes. They have both mental and physical components. a) The mental components are 1. Cognition – means awareness of a sensation and it cause or recognition. 2. Affect: - is development of a feeling and its associated effect like pleasantness or unpleasantness. 3. Conation is the urge or desire to take action. b) Physical changes or expressions include 1. Various autonomic responses such as increase in heart rate, blood pressure sweating etc and 2. Some important emotions include rage, fear, grief, joy, excitement etc. Areas of brain concerned with emotions are the limbic system and hypothalamus. Rage- Results from stimulation of periventricular nuclei and lateral hypothalamus in animals. It is characterized by defensive posture, hissing, snarling, wide one eyes and dilated pupils. Rage is a release phenomenon and normally is held in check by neocortex and ventromedial nucleus. Fear (Panic) reaction is evoked by stimulation of preoptic area of hypothalamus and amygdaloid nucleus. It is manifested as cowering, escape, papillary dilation, sweating increases in heart rate and blood pressure. Suggestions: facebook.com/asifpatel.ggmc

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150 *Q. Parkinson’s disease:

Named after James Parkinson. Results from damage to neurons in substantial nigra (pars compacta) and depletion of dopamine in the nigrostriatal pathway. These effects can be seen in various conditions like 1. Old age (paralysis agitans) 2. Drug toxicity from reserprine, MPTP, 3. Trauma (as seen in boxers) 4. viral infections. 5. Wilson’s disease.

Pathophysiology:- Loss of dopamine results in overactivity of inhibitory pathway from striatum to globes pallidus and therefore disinhibition of VA and VL nuclei of thalamus leading to greater discharge of motor cortical neurons to spinal motoneurons especially gamma neurons.

Clinical Features: - 1. Poverty of movements (Akinesia or hypokinesia). Patient has great difficulty in initiating voluntary movements. 2. Loss of automatic and associated movements., like swinging of arms while walking. 3. Loss of facial expressions (mask like face) 4. Loss of gestures. 5. Posture and gait :- Patient stand in a position of forwards flexion and has tendency to fall forwards. He takes short, quick shuffling steps to prevent fall (shuffling or festinant gait). 6. Rigidity of muscles involving flexors and extensor causing continuous resistance (lead pipe rigidity) to passive movements. 7. Tremors :- There are coarse tremors 4 to 6/sec. Affecting fingers, wrists or neck muscles. They are present at rest (static tremors) and disappear during activity. They are described as pill rolling tremors, drum beating tremors etc. Treatment :- 1) Administration of L dopa which crosses BBB and forms dopamine. 2) Bromocriptine which is a dopamine agonist. 3) Discontinue reserpine. Aphasia:-

It is disorder of language function of brain due to lesions in higher cortical centres in dominant (categorical) hemisphere. Here the sense of vision, hearing and the articulation mechanism for speech is normal. Types of aphasia: - 1. Wernicke’s : Damage to post part of sup temporal gyrus. The person can hear the spoken word or can see the written word but fails to understand the general meaning or the thought that is conveyed (semantic defect) 2. Sensory aphasia : Damage to auditory association area causes inability to understand spoken word (word deafness) or damage to visual association area in angular gyrus causes inability to understand written word (word blindness or dyslexia) 3. Nominal aphasia (anomia) : If the lesion is in lower occipitotemporal association area, then the patient is not able to name the objects. Hence called nominal aphasia. 4. Motor aphasia (No fluent) : is due to lesion in Broca’s speech area situated in front of lower tip of precentral gyrus. The person knows what he wants to say but cannot activate motor neurons for speech, hence be cannot emit words. 5. Global aphasia: - is due to extensive lesion involving wernicke’s, broca’s and auditory and visual association areas. Here all aspects of speech function are severely affected. 6. Conduction aphasia: - results from damage to arcuate fasciculus which conducts impulses from wernicke’s to broca’s area. *Q. Conditioned Reflexes

Def :- A conditioned reflex is a reflex response to a stimulus (conditioned stimulus) which normally does not elicit that response but, which is acquired by repeatedly pairing that stimulus with another stimulus (unconditioned) which normally produces that response. Types:- 1) Classical (pavlovian) conditioning :- Studied in dogs. A bell is sounded before giving food to the dog and on presentation of food the dog salivates. This procedure is repeated many times and then it is observed that dog salivates in response to sound of bell even if food is not presented. Suggestions: facebook.com/asifpatel.ggmc

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2) Operant Conditioning:- Here, the animal learns to perform some task to obtain reward or to avoid punishment like bar pressing. 3) Autonomic conditioning. Characteristics of conditioned reflexes:- a. Always acquired b. May be established or abolished. c. Always dependant on preexisting unconditioned reflexes. d. Conditioned stimulus must precede unconditioned Reflexes. Basis of cond. reflexes: They are due to formation of new synaptic circuits in the brain following repeated presentation of CS and US. Thus in classical conditioning, new connections develop between auditory pathway and salivary centre. Significance of cond. reflexes:- They form the basis of learning which is defined as predicable change in behavior following a sensory experience. They are the basis of most of our habits and social behavior. *Q. Upper Motor Neuron Lesion:

Upper motor neurons are those which end on spinal motor neurons sending their fibers through pyramidal as well as extrapyramidal pathway: These neurons or their fibers may be damaged by tumor, trauma or thrombosis. Manifestations of UMN lesions are : 1. Loss of voluntary movements especially skilled distal movements (pyramidal). 2. There is loss of power in the affected muscles (paralysis). Paralysis may involve one half of body (hemiplegic seen in lesions at internal capsule), both lower limbs (paraplegia in spinal transaction), all 4 limbs (paraplegia) or one limb (monoplegia). 3. Hypertonia: Tone of the muscles is increased (Spastic paralysis) due to increased activity of gamma neurons especially if there is involvement of extra pyramidal pathways. It may appear as Clasp Knife spasticity due to increased tone of flexor muscles. Which suddenly gives way on stretching or lead pipe rigidity due to spasm of flexors and extensors (parkinson’s disease) or Cog wheel rigidity (tremors superimposed on rigidity). Isolated damage to pyramidal tracts causes hypotonia. 4. Loss of superficial reflexes like abdominal, cremastric due to interruption of reflex arc. 5. Babinski sign : There is dorsi flexion of great tone and fanning out of other tones. It is a release phenomenon and is characteristic of pyramidal tract damage. 6. Tedon reflexes :- Like biceps jerk, knee jerk etc. are exaggerated due to increased muscle spindle sensitivity. 7. Clonus: Patellar clonus and ankle clonus may be seen due to oscillations of muscle spindle stretch reflex mechanism. 8. There is no atrophy of muscles because LMN are intact. 9. Reaction of degeneration is absent. 10. Abnormal movements like athetosis, ballismus etc. may be seen. Complete Transection of Spinal Cord:-

Seen in gunshot injuries or trauma from accidents, fall from height etc. Three stages are observed:

1) Stage of spinal shock :- Results from sudden removal of impulses from higher centres and is characterized by a) flaccid paralysis b) loss of all reflexes. c) Loss of all sensations below the lesion d) Loss of sphincter tone and e) Loss of autonomic function including vasomotor paralysis. This stage lasts for 3-4 weeks in human beings. 2) Stage of reflex activity :- a) There is gradual increase in tone of flexor muscles and they become hypertonic (spastic paralysis). Both lower limbs are in a state of flexion (paraplegia in flexion) b) Babinski sign present. c) Mass reflex may be seen in which scratching below the lesion, causes strong flexor spasms, evacuation of bladder and bowels, sweating etc. d) Urinary bladder becomes automatic e) later stretch reflexes become hyperactive, clonus may present. (In incomplete transection, extensor tone and reflexes return first producing paraplegia in extension) f) Voluntary movements and sensation never return. This stage is due to gradual recovery of spinal neurons. Suggestions: facebook.com/asifpatel.ggmc

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152 3) Stage of reflexes failure: - Is due to degeneration of spinal neurons a) Reflexes disappear b) Muscles become hypotonic and then flaccid and undergo wasting. (Reaction of degeneration present) c) Mass reflex disappears d) Sluggishness of circulation leads to development of bed sores e) Bladder infection may develop and ultimately the patient may die from septicemia. Transection above C3 may cause death due to paralysis of diaphragm.

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ENDOCRINE SYSTEM

Chapter 10

*Q. Describe Physiological Action Regulation of Human Growth Hormone :

Growth hormone is a polypeptide hormone containing 191 amino acids secreted by somatotroph cells of anterior pituitary.

Physiological Actions: 1) Effects on growth: It is a generalized growth promoting hormone acting on almost all body cells. A) Skeletal growth: Long bones – GH stimulates growth of epiphyseal cartilages and causes widening of epiphyseal plates. This action results from a) Proliferation of chondrocytes and osteogenic cells b) They lay down more bone matrix and chondroitin sulphate c) Conversion of chondrocytes into osteogenic cells d) conversion of proline to hydroxyproline leading to formation of collagen. It therefore brings about increase in the length of long bones. After fusion of epiphyses, girth of long bones increases. On flat bones : GH increases size and thickness of flat membranous bones. B) Soft tissue growth:- GH stimulates growth of soft tissue by causing hypertrophy (increase in size) and hyperplasia (proliferation) of cells. It thus causes growth of muscles and organs like liver, stomach, intestine, tongue, heart etc.

2. Effects on Metabolism: - a) Protein metabolism: - GH stimulates protein synthesis by i) increasing amino acid transport into cells and ii) stimulating transcription of DNA and translation of MRNA. It also decreases breakdown of protein and thus has protein anabolic effect. b) Carbohydrate metabolism: - i) GH decreases glucose utilization by cells by making FFA available ii) Promotes glycogen deposition iii) Decreases glucose uptake by cells. It therefore produces hyperglycemia (diabetogenic effect). c) Fat metabolism : i) GH stimulates lipolysis and increases FFA levels ii) Promotes conversion of fatty acids into acetyl CoA and its utilization thus sparing proteins and glucose. iii) Promotes formation of acetoacetic acid (ketogenic effect). 3. Other actions : a) Lactogenic effect- Promotes milk secretion and growth of breasts b) increases CA absorption from GIT. c) stimulates erythropoiesis d) Growth of thymus. e) Stimulates insulin secretion f) Causes positive nitrogen balance. Mechanism of action : Some actions of GH, especially on protein synthesis and fat metabolism are its direct actions, but its actions on skeletal or soft tissue are due to Somatomedins. These are small polypeptides formed in the liver cells and fibroblasts by the action of GH. They are of 4 types A, B, C, and D of which Somatomedin C, also called Insulin Like Growth Factor I, is most important physiologically.

Regulation: GH secretion is entirely regulated by 2 hypothalamic hormones: 1. Growth Hormone Releasing Hormone which promotes release of GH and 2. Growth Hormone Inhibiting Hormone; these are transported through hypophyseal portal vessels and act on somatotropes. A) Stimuli which act on hypothalamus and promote release of GH are :- 1. Deficient nutritional states like starvation, hypoglycemia, cellular protein depletion, low FFA levels, fasting etc. 2. Exercise. 3. Trauma. 4. Anxiety and stressful stimuli 5. Deep Sleep (NREM) 6. Increased arginine levels. B). Stimuli Suggestions: facebook.com/asifpatel.ggmc GGMC MUMBAI

154 which inhibit GH Secretion: 1. Increased levels of GH have a negative feedback effect on GH secretion. This is due to inhibitory action of somatomedin C on hypothalamus. 2. Increased FFA levels 3. Somatostatin produced by pancreas. 4. Hormones like progesterone, cortisol 5. REM Sleep. Applied :- Hypersecretion of GH leads to Gigantism (before epiphyseal fusion) or Acromegaly (in adults). Hyposecretion produces dwarfism in children & Simmond’s disease in Adults.

*Q. Enumerate The Hormones Secreted By Anterior Pituitary. Describe Physiological Actions And Regulation of Secretion of Prolactin :

Hormones secreted by ant pituitary are: 1. Human Growth Hormone (by somatotropes) 2. Thyroid stimulating Hormone (by thyrotropes). 3. Adrenocorticotropic Hormone (by corticotropes) 4. Follicle stimulating hormone (Gonadotrophes). 5. Luteinizing Hormone or ICSH (Gonadotrophes) 6. Prolactin (lactotrophes). In addition, cortictrotrophes secrete small amounts of 7. beta lipotropin. 8. beta endorphin. 9. Gamma Melanocyte stimulating hormone.

Prolactin or Leutotrophic hormone is a polypeptide hormone containing 198 amino acids and is produced by lactotrophes. It's secretion starts increasing after 5th week of pregnancy and continues as long as mother breast feeds her baby(lactation period).

Physiological actions:- 1. Lactogenic effect :- Prolactin initiates milk secretion after birth of the baby. During pregnancy, estrogens and progesterone act on breast causing proliferation of alveoli and ducts. Thus milk secreting apparatus becomes ready, but there is no secretion of milk during pregnancy because the lactogenic action of prolactin is suppressed by high levels of estrogen and progesterone. After birth of baby, placenta is expelled, levels of these hormones fall and prolactin becomes effective. 2. Galactopoiesis: Prolactin causes continuation of milk secretion during nursing period. This action requires adequate quantities of other hormones like growth hormone (promotes protein synthesis) cortical (mobilizes amino acids for protein synthesis), and parathyroid hormone (makes Ca ions available for secretion in milk) 3. Growth of breasts :- Prolactin causes proliferation of glandular tissues of the breasts during pregnancy along with other hormones like estrogen, progesterone, human chorionic somatomamotropin etc. 4. Prolactin has inhibitory effect on gonadotropic hormones: It therefore suppresses ovarian cycles and ovulation in nursing mothers (natural contraception) 5. In males, prolactin increases the number of LH receptors on Leydig’s cells of testis and therefore potentiates the action of LH in causing more secretion of testosterone. 6. In rats, it maintains corpus luteum (luteotrophic action). 7. In birds, it stimulates secretion of crop sacs and maternal behavior.

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Mechanism of action :- Prolactin activates mRNA in mammary gland cells and stimulates its translation leading to formation of enzymes which produce milk components like casein, lactalbumin, lactoglobulin, lactose etc. Regulation:- Prolactin secretion is controlled by 2 hypothalamic hormones. 1. Prolactin inhibiting hormone (dopamine) which inhibits release and 2. Prolactin releasing hormone which promotes release. These hormones reach ant. pituitary through hypophyseal portal vessels. Various Stimuli which affect prolactin secretion are : 1. Suckling : Stimulates tactile receptors in nipple and areola and afferent impulses are carried to hypothalamus. Prolactin is released in spurts each spurts lasting for about 1 hours. Released prolactin promotes milk secretion. 2. Exercise, sleep, surgical and emotional stress stimulates prolactin secretion. 3. Oestrogens stimulate prolactin secretion during pregnancy. 4. L dopa inhibits prolactin secretion. Prolactin deficiency leads to inadequate milk secretion.

*Q. Describe The Physiological Actions and Regulation of Secretion of Antidiuretic Hormone:-

ADH or vasopressin is a peptide hormone containing 9 amino acids and is secreted by neurons of supra optic nucleus (85%) and of paraventricular nucleus (15%). It is released into circulation from post pituitary.

Physiological Actions:- 1. Anti-Diuretic Action :- ADH increases water reabsorption from the kidneys and allows concentrated urine to be excreted. After its release, it reaches the kidneys through circulation and acts on the cells of collecting duct and distal tubule. It increases permeability of these cells to water and urea. Hence water is drawn into hypertonic medullary interstitium by osmosis. Thus, large quantities of water are retained in the body and urine volume decreases. By controlling water reabsorption, it plays an important role in regulating osmolarity of plasma, volume of ECF, blood volume and therefore blood pressure.

Mechanism: 1. ADH Combines with V2 receptors on basal surface of target cells and activates adenyl cyclase leading to formation of cAMP which then causes formation of vesicular structures that get incorporated into luminal surface of cells and acts as channels through which water and urea can pass. 2. Vasopressin action is seen when ADH is secreted in large quantities. It causes strong contraction of smooth muscle of arterioles and raises arterial pressure. In physiological quantities it accounts for only 5 to 10 mm of blood pressure. Mechanism :- ADH combines with V1 receptors on vascular smooth muscle, activates phospolipase C leading to rise in intracellular Ca and contraction. 3. In high conc. ADH causes contraction of smooth muscle of uterus, gall bladder and urinary bladder. 4. Acts as neurotransmitter in nervous system.

Regulation: - ADH secretion is regulated by 1. Osmolarity of plasma :- Increased osmolarity stimulates osmoreceptors of hypothalamus which activate supraoptic neurons to release ADH. This ADH then causes water retention in body without affecting solute excretion. Thus osmolarity comes back to normal. Opposite changes occur when osmolarity falls. Thus ADH regulates osmolarity of ECF. 2. ECF Volume: - Normally the volume receptors in atria and great veins have inhibitory effect on supraoptic neurons. Therefore when ECF volume and venous return falls, there is disinhibition of these neurons and ADH is secreted, which causes retention of water. Thus ECF volume comes back to normal, opposite changes occurs when ECF volume rises. Thus ADH controls ECF volume and blood volume. 3. Fall in arterial pressure :- Normally, baroreceptor discharge has inhibitory effect on ADH secretion. When blood pressure falls, this inhibition is removed and large quantities of ADH are secreted, which raises blood pressure by its immediate vasoconstrictor action and by its long term fluid retaining action. 4. Conditions like hemorrhage, dehydration and shock stimulates ADH secretion by above mechanism. 5. Anxiety, emotional stress stimulate ADH secretion. 6. Exercise Suggestions: facebook.com/asifpatel.ggmc

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156 stimulates. 7. Angiotensin II and drugs like morphine stimulate ADH. 8. Alcohol inhibits ADH and produces diuresis. Applied aspects :- Deficiency of ADH leads to a condition called diabetes insipidus characterized by polyuria, polydypsia and urine of low specific gravity. *Q. Describe the Physiological Action and Regulation of Secretion of Thyroid Hormones:The principal thyroid hormones are 3, 5, 3', 5' Tetraindothronine or thyroxine (T4) ;

3, 5, ' Tri – iodothyronine (T3) and Calcitonin. Physiological actions :- (1) Calorigenic effect:- Thyroid hormones increase metabolism in most body cells except those of brain, testis, and spleen. They increase BMR, heat production and body temperature. Calorigenic effect is due to increased activity of Na-K ATPase. (2)Protein metabolism:- In moderate conc., they promote protein synthesis by stimulating transcription and translation. Number and quantity of intracellular enzymes is increased. In high conc. they have catabolic effect. (3) Growth:- they are essential for normal growth and maturation, especially growth of brain and myelination. Their effects are permissive to those of growth hormone. (4) Carbohydrate metabolism:- thyroid hormones stimulate glycogenolysis, neoglucogenesis and glucose absorption from GIT leading to hyperglycemia. (5) Fat metabolism:- They stimulate lipolysis and increase FFA levels. They also accelerate oxidation of fatty acids in the cells. They promote excretion of cholesterol and phospholipids. (6) Effects on CVS :- a) Increased tissue metabolism increases venous return and hence cardiac output. b) Increase in heart rate and force of myocardial contraction by direct action on enzymes and by potentiating effects of catecholamines on heart. They increase the no. of beta adrenergic receptors in heart. c) Rise in systolic pressure. d) Fall in diastolic pressure due to metabolic peripheral vasodilation. e) Peripheral resistance falls. f) Pulse pressure widens but mean pressure remains same. g) There is hyper dynamic circulation. (7) Nervous system:- Thyroid hormones are essential for normal alertness, normal reaction time and normal reflexes. (8) GIT: - they increase appetite and food intake. Secretions and motility of GIT is also increased. (9) Respiratory system :- Increase in rate and depth of respiration due to O2 consumption and CO2 production. (10) Bones and muscles:- In high conc. thyroid hormones cause mobilization of bone matrix and breakdown of muscle proteins. (11) Endocrine:- They stimulate secretion of insulin PTH and accelerate inactivation of glucocorticoids in liver. (12)Other: a)Gonads: Thyroid hormones are essential for normal sexual functions. (b) Mobilization of mucopolysaccharides from skin. (c) They stimulate production of erythropoietin and (d) surfactant secretion. Mechanism of action : In most target cells T4 is converted into T3 by deiodinase. T3 then moves into nucleus, combines with receptor and then stimulates transcription and translation to form new protein (enzymes) responsible for actions of thyroid hormones. Regulation:- Secretion of thyroid hormones is almost entirely regulated by the TSH secreted by ant. pituitary. TSH increases synthesis of thyroid hormone by stimulating. A) Iodide pump. B) Iodination of tyrosine and C) coupling of MIT and DIT. It promotes release of thyroid hormones by increasing endocytosis and proteolysis of colloid. It also increases size and vascularity of thyroid gland. TSH secretion in turn, is regulated by 1) Negative feedback effect of circulating T3 and T4. Thus TSH controls thyroid activity and thyroid Suggestions: facebook.com/asifpatel.ggmc

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hormones control TSH secretion. This is the day to day control mechanism for secretion of thyroid hormones. 2) TRH from hypothalamus stimulates TSH secretion especially in conditions like exposure to cold. 3) Somatostatin (GHIH) produced by hypothalamus inhibits TSH. 4) Stress stimuli and glucocorticoids inhibit TSH. Applied aspects: -Hypersecretion of thyroid hormones produces Grave’s disease while hypo secretion produces myxedema (adults) or cretinism in children.

*Q. DESCRISE THE PHYSIOLOGICAL ACTIONS AND REGULATIONS OF SECRETION OF PARATHORMONE : PTH is a polypeptide hormone containing 84 amino acids secreted by chief cells of parathyroid gland. Its single most important action is to increase serum Ca+ levels and therefore it plays an important role in calcium homeostasis. (Normal serum Ca+- 9 to 11 mg % of which 50% is in ionic form) Physiological actions:- PTH acts on 3 sites to increase serum Ca+. (1) Action on bones: - It increases reabsorption of Ca+ and phosphate from bones. This occurs in 2 phases: a) Rapid phase (osteolysis) : Which shows effect within 10 minutes. Here PTH increases permeability of osteocytes and osteoblasts, which form osteocyte membrane, to Ca+ so that Ca diffuses from bone fluid (hydroxyapatite crystals) into these cells and from these cells it is pumped into the ECF by Ca pump. It thus indirectly increases activity of Ca+ pump by making more Ca ions available for its action. b) Slow phase of Ca reabsorption: results from breakdown of organic matrix of bones which also leads to release of Ca +. This action is brought about by osteoclasts. PTH causes activation of osteoclasts and stimulates formation of new osteoclasts. These cells then release acids like lactic acid, citric acid etc. and also various proteolytic enzymes which cause dissolution of bone matrix. Prolonged action of PTH on bones leads to osteoporosis. (2) Action of kidneys: - PTH increase Ca+ reabsorption from the kidneys and therefore decreases Ca+ excretion. This decreases phosphate reabsorption from proximal convoluted tubule and therefore increases PO4 excretion (Phosphaturia). Thus PTH causes fall in plasma PO4 levels. It also increases reabsorption of Mg++ and H+ ions but decreases absorption of Na+, K+ and amino acids. (3) Formation of 1, 25Dihydroxycholecalciferol:- PTH activates the enzyme 1 alpha hydroxylase in cells of PCT and promotes conversion of 25HCC into 1,25 DHCC. This hormone a) increases Ca+ absorption from intestine. b) Increases activity of Ca+ pump in osteocytes membrane and c) increases Ca+ reabsorption from kidney. It thus potentiates the Ca+ raising action of PTH. Mechanism of action:- PTH combines with receptors on the surface of target cells and activates adenyl cyclase leading to formation of cAMP, activation of protein kinase and phosphorylation of various proteins which then produce the effect of hormone. Regulation of secretion:- 1. Serum ionized Ca+ level is the most important factor regulating PTH secretion. Ca+ levels have a direct negative feedback effect. A slight fall in Ca+ increases PTH secretion 2-3 times which then restores serum Ca+. Rise in Ca+ level inhibits PTH secretion and thus Ca+ is allowed to be deposited in bones. 2. Magnesium levels in serum also have a similar effect, decrease in Mg++ stimulates PTH secretion. 3. Activation of sympathetic system also stimulates PTH secretion. Applied aspects: -Hyposecretion of PTH leads to hypocalcaemia which produces a condition called Tetany in which there is increased irritability of nerves and spasm of muscles which can be fatal. *Q. DESCRIBE THE ROLE PLAYED BY VARIOUS HORMONES IN CALCIUM HOMEOSTASIS: Calcium homeostasis is maintenance of constant levels of serum calcium. Normally serum Ca+ is maintained at conc. of 10 mg% (range 9-11mg %) of which 50% is in ionized form. Importance of Ca+ homeostasis: Regulation of ionized calcium within a narrow range is must because Ca+ ions have an important effect on excitability of nerve and muscle tissue. Suggestions: facebook.com/asifpatel.ggmc

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158 Hypocalcaemia increases permeability of membrane to Na+ ions, thus nerves and muscles become hyper excitable leading to spasm of muscle, a condition called Tetany; which can be fatal. Calcium homeostasis is brought about by two mechanisms:- 1)Buffer function of exchangeable Ca+ in bones :- About 1% of bone Ca+ is in exchangeable form such as CaHPO4. When blood Ca+ rises, more of this Ca+ is deposited in bones thus lowering Ca+ levels. When blood Ca+ falls, bone Ca is mobilized to restore blood Ca+. 2)Role of hormones:- Hormones that increase plasma Ca+ when Ca+ level falls are: A) Parathyroid hormone: - Secreted by chief cells of parathyroid glands when serum Ca+ falls. It raises plasma Ca+ by following actions. 1) Action on bones :- a) Rapid phase :- PTH increases permeability of osteocyte membrane (osteocytes end osteoblasts) to Ca+ ions, so that Ca+ ions diffuse from bone fluid into these cells from where they are pumped out into ECF by Ca+ pump. b) Slow phases: PTH increases number and activity of osteoclasts which cause dissolution of organic matrix of bone and release Ca+ ions. 2) Kidneys: - PTH increases reabsorption of Ca+ from distal tubule and decreases Ca+ excretions . 3) It also stimulates formation of calcitriol. B) 1,25, Dihydroxycholecaciferol (calcitriol) :- It is a metabolite of Vit D3 formed in cells of PCT of kidney by the action of 1-alpha hydroxylase which converts 25HCC into 1,25 BHCC. It raises serum Ca+ by following actions:- 1) It increases Ca+ absorption from intestine : Acting at nuclear level, it causes formation of new protein called calcium binding protein in the brush border of intestinal lumen into the cells. 2) Calcitriol also increases activity of Ca+ pump in osteocyte membrane and promotes transfer of Ca+ ions from bone fluid into ECF. 3) It increases reabsorption of Ca+ ions from renal tubules. Thus this hormone potentiates the effects of PTH in raising serum Ca+. Hormone that decreases serum Ca+ when Ca+ level rises is Calcitonin. It is secreted by parafollicular or C cells of thyroid gland in response to rise in serum Ca+. 1. It inhibits bone reabsorption by inhibiting osteoclasts and by decreasing formation of new osteoclasts. It therefore shifts the balance towards deposition of Ca+ in the bones thereby lowering serum Ca+. However this effect is weak in adults (than in children) due to slower rate of bone turnover. 2. It also decreases Ca+ reabsorption from kidneys and from intestine. Hypocalcaemic effects of calcitonin are weak and short lasting (due to suppression of osteoclasts) therefore it plays a relatively minor role as compared to PTH in long term regulation of serum Ca+. It is useful in preventing hypercalcemia after meals. *Q. DESCRIBE THE PHYSIOLOGICAL ACTIONS AND REGULATION OF SECRETION OF INSULIN: Insulin is a polypeptide (51 AA) hormone secreted by beta cells of pancreas. Physiological actions :A) Carbohydrate metabolism: 1.Promotes glycogen synthesis in liver and muscles by activating concerned enzymes. 2. Inhibits gluconeogenesis by inhibiting transaminases, deaminases and by reducing availability of substances. 3. Increases transport of glucose in the most cells (except brain, RBC’s, liver cells) by increasing activity of glucose transporter. 4. Increases glucose utilization by the cells (protein sparing action). 5. Inhibits glycogenolysis by inhibiting liver phosphorylase. 6. It therefore increases blood glucose levels (Hypoglycemic action). B) Fat metabolism :- 1. Lipogenic effect – excess glucose in liver cells is converted to acetyl CoA and then to fatty acids. 2. Promotes storage of fats in adipose tissue by a) activating lipoprotein lipase and by b) promoting glucose transport into adipose cells which provides alpha glycerophpsphate and glycerol for synthesis of triglycerides. 3. Inhibits mobilization (lipolysis) of stored fats by inhibiting Hormone Sensitive Lipase and thus decreases FFA levels. 4. Antiketogenic effect : Insulin decreases formation and release of acetoacetate acid in liver and increases its utilization by the cells. C) Protein metabolism : 1. Insulin promotes protein synthesis (anabolic effect) by a) stimulating transcription and translation processes b) increasing transport of amino acids into the cells. 2. It also inhibits breakdown of proteins by increasing glucose utilization. D. Mineral metabolism: promotes Suggestions: facebook.com/asifpatel.ggmc

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entry of K+ ions into the cell and tends to produces hypokalemia. E. Effects on growth : Insulin exerts a synergistic action with growth hormones in promoting growth of the body by its protein anabolic action. Mechanism of action : It combines with specific receptors (2 Alpha and 2 beta subunits) on target cell, enters the cell (internalization) and activates mRNA for some effects and suppresses cAMP for others. Regulation of secretion:- A) Regulation by substrates : 1. Blood glucose :- is the most important factor controlling insulin secretion rise in glucose (above 110 mg %) stimulates, while fall in glucose inhibits insulin secretion. Glucose enters beta cells ad its metabolic product promotes insulin release. Secreted insulin then transports glucose back to normal. 2. Amino acids like arginine and lysine stimulate insulin secretion and potentiate affects of blood glucose on insulin secretion. B) Hormonal regulation :- 1. GIT hormones like Gastric Inhibitory peptide, Gastrin, CCK etc. which are released after meals stimulate insulin secretion and prevent excess hyperglycemia following meals. 2. Pancreatic hormones: - glucagon increases while somatostatin inhibits secretion of insulin by their paracrine effects. 3. Other hormones : like growth hormone, thyroid hormones, cortisol, estrogens, progesterone and epinephrine, all stimulates insulin secretion by increasing blood levels of glucose or amino acids C) Neural regulation :- stimulation of right vagus innervating pancreas increases insulin secretion while stimulation of symp fibers has opposite effects. Applied physiology :-Absolute or relative deficiency of insulin produces Diabetes Mellitus characterized by hyperglycemia, polyuria, polydypsia and polyphagia. *Q. DESCRIBE THE ROLE OF HORMOES IN GLUCOSE HOMEOSTASIS: Glucose homeostasis is the maintenance of blood glucose at a constant value or within a narrow range. Normal blood glucose levels are 80 to 100 mg/100ml. Importance: - Glucose homeostasis is essential because: 1. Fall in blood glucose effects functions of cells of brain, retina and germinal epithelium which depend only on glucose as their nutrient. 2. Rise in blood glucose increases osmolarity of blood causing diuresis and dehydration. 1)INSULIN:- is the only hormone that lowers blood glucose. When blood glucose rises (eg. After meals) insulin secretion is stimulated which produces various effects like 1. Deposition of glucose as glycogen in liver and muscle cell 2. Increases glucose transport into cells, 3.increases glucose utilization by cells and 4.Inhibits neoglucogenesis. All these effects prevents excess rise in blood glucose. During fasting blood glucose level decreases (hypoglycemia), insulin secretion is reduced and liver glycogen is mobilized to maintain as buffer (glucostat) and prevents large changes in blood glucose. 2. Growth hormone :- Secretion is stimulated by hypoglycemia, and raises blood glucose by reducing uptake of glucose and by decreasing peripheral utilization of glucose. Prolonged hyper secretion of GH (gigantism) can lead to pituitary diabetes. 3. Glucagon: - is stimulated by fall in blood glucose and it increases blood glucose by 1. Stimulate glycogenolysis in the liver cells by activating phosphorylase via cAMP mechanism and 2. Stimulates neoglucogenesis by activating enzymes that convert by pyruvate to phosphoenol pyruvate, transaminases and deaminases. Suggestions: facebook.com/asifpatel.ggmc

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160 4. Thyroid hormones :- increase blood level by 1. Stimulating glycogenesis and 2.Neoglucogenesis in liver cells and by increasing glucose absorption from GIT. 5.Cortisol (glucocorticoids): Brings about increase in blood glucose by stimulating glycogenolysis and by decreasing peripheral utilization of glucose. Long standing hyperglycemia of adrenal origin can cause exhaustion of insulin secretion by beta cells of pancreas leading to adrenal diabetes. 6. Epinephrine :- Increases blood glucose level by a) increasing breakdown of glycogen in liver b) decreasing peripheral utilization of glucose c) stimulating glycogenolysis sympathetic stimulation produces similar affect. 7) Oestrogens : have mild hyperglycemic action. *Q. DESCRIBE PHYSIOLOGICAL ACTION AND REGULATION OF SECRETION OF ALDOSTERONE. Aldosterone is a mineralocorticoid secreted by zona glomerulosa of adrenal cortex. Physiological actions :- 1. On renal tubules :- a) Aldosterone acts on distal convoluted tubule collecting tubule and collecting duct and increases reabsorption of Na+ ions and promotes excretion of K+ ions. It thus causes conservation of Na+ ions in the body. Along with Na+ ions, water is also retained leading to increase in ECF volume. However, effects of aldosterone in causing Na+ retention and increased ECF volume disappear after few days, a phenomenon called aldosterone escape, which results from pressure natriuresis, diuresis and secretion of atrial natriuretic hormone, b) tubular secretion of K+ is one of the important mechanisms for k+ elimination from body and for prevention of hyperkalemia. c) To a lesser extent, aldosterone also promotes secretion of H+ ions into the renal tubule in exchange for reabsorbed Na++ ions. This action increases acidity of urine and is especially seen in acidosis to eliminate H+ ions. 2.On CVS :- By increasing ECF volume, aldosterone plays an important role in regulation of blood volume and in long term regulation of arterial pressure. Excess aldosterone causes volume loading type of hypertension. 3.On sweat glands:- It increases reabsorption of Na+ and Cl- from primary sweat secretion and promotes K+ excretion. This effect is especially important when large quantity of sweat is secreted (acclimatization to hot weather) . 4. On salivary glands it increases reabsorption of Na+ and Clfrom primary secretion and promotes K+ excretion by acting on duct cells. 5. GI tract : aldosterone increases Na+ absorption from stomach, small intestine and colon. Mechanism of action: - aldosterone enters the cytoplasm of target cell and combines with receptor protein in cytoplasm. The HR complex moves into nucleus, binds with specific part of DNA and stimulates transcription to from mRNA which is then translated by the ribosomes to form new proteins which 1) increase the activity of Na+ K+ pump 2) increase cell permeability Na+ ions 3) provide more energy for Na+ K+ pump. Regulation of aldosterone secretion:- 1) rise in plasma K+ levels : stimulates aldosterone secretion leading to increased K+ secretion and restoration of normal K+ conc. 2) Renin Angiotensin mechanism:- Decreased blood flow to kidney (due to decreased blood volume ), fall in arterial pressure or increased sympathetic discharge causes release of renin from JG cells leading to formation of Angiotensin II which stimulates aldosterone secretion by activating desmolase. The aldosterone then restores ECF volume and blood pressure. 3. ACTH : produced by corticotropes of ant. pituitary has a weak and transient effect in stimulating aldosterone secretion (permissive effect) 4. Decrease in total body Na+ can also stimulate aldosterone secretion by Renin-Angiotensin mechanism to conserve Na+ ions in the body. Applied aspects: - Because of its effects on ECF volume, blood volume and blood pressure, it is considered a lifesaving steroid. Hyperaldosteronism is associated with hypokalemia and hypertension, while hypoaldosteronism leads to hyperkalemia, decreased blood volume, acidosis, decreased cardiac output and shock. Suggestions: facebook.com/asifpatel.ggmc

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161 *Q. DESCRIBE THE PHYSIOLOGICAL ACTIONS AND REGULATION OF SECRETION OF GLUCOCORTICOIDS: Glucocorticoids include cortisol, corticosterone and deoxycorticosterone. They are secreted by zona fasciculata and reticularis of adrenal cortex. Physiological actions :- A) Metabolic actions :- 1) carbohydrate metabolism : a) In liver cells, they stimulate gluconeogenesis by increasing activity of transaminases, deaminases and by increasing availability of amino acids b) decrease peripheral utilization of glucose. c) Therefore they produce hyperglycemia, which if severe, can lead to adrenal diabetes mellitus. d) They also increase glycogen deposition in liver. 2) Protein metabolism :- a) In hepatic cells, cortisol promotes protein Synthesis by stimulating concerned enzymes and by increasing transport of amino acids into the cells. b) In extra hepatic tissue cortisol increases protein breakdown, decreases transport of amino acids into cells, causes cellular protein depletion and increase in blood level of amino acids. 3) Fat metabolism: - cortisol a) promotes lipolysis in adipose tissue by activating hormone sensitive lipase b) stimulates oxidation of fatty acids in the cells and c) increases FFA levels B) Other effects. 4. Role in stress :- cortisol helps in stress conditions by a) mobilizing fatty acids and amino acids which can be used for energy and for synthesis of new substances (like stress proteins) b) increasing sensitivity of vasculature to circulating catecholamines (permissive action). 5. Anti inflammatory and antiallergic action :- Cortisol has a suppressing effect on inflammation (including allergic) changes. It a) stabilizes lysosomal membrane b) reduces release of vasodilator peptides c) reduces permeability of capillaries and d) prevents migration of leucocytes. 6. Cortisol decreases the number of circulating eosinophils and lymphocytes. 7. It suppresses immune response; humoral as well as cellular by its lympholytic and protein catabolic action. 8. It has mild mineralocorticoid action i.e. causes retention of Na+ and water. 9. Stimulate erythropoiesis. 10. Stimulates surfactant secretion in late fetal life. 11. Stimulates HCl secretion in stomach. 12. Cortisol reduces absorption of Ca+ from GIT and kidneys and causes osteoporosis. Mechanism of action :- Being a steroid hormone, cortisol stimulates transcription and translation leading to formation of new proteins which are responsible for its action. Regulation of secretion:ACTH :- produced by ant. pituitary is the most important factor controlling cortisol secretion. It stimulates cortisol secretion by activating desmolase. ACTH secretion is controlled by corticotropin releasing factor (CRF) from hypothalamus and by blood cortisol level. 2. Negative feedback effect: Increased levels of cortisol have a direct negative feedback effect on hypothalamus suppressing CRF release and more importantly on ant. pituitary inhibiting ACTH secretion, thus cortisol levels are brought back to normal. 3. Stress condition like acute pain, high fever, trauma, emotional tension etc. act on hypothalamus and stimulate secretion of CRF-ACTH- Cortisol. 4. Circadian rhythm: of cortisol secretion results from a similar rhythm of CRF and ACTH, blood levels being highest in the early morning and lowest in evening. It is due to impulses from suprachiasmatic nucleus. Applied Physiology: - Hypersecretion of cortisol produces Cushing's syndrome (moon face, buffalo hump, purple abdominal striate) while hyposecretion produces Addison’s disease (pigmentation) *Q. WHAT ARE THE HORMONES SECRETED BY ADRENAL MEDULLA? DECRIBE THEIR ACTIONS. The chromaffin cells of adrenal medulla secrete following hormones. 1. Epinephrine (adrenaline ) 2. Norepinephrine (noradrenaline) 3.Dopamine and trace quantities of 4.Metencephalin.5. Leu encephalin. Actions of Epinephrine :- 1.On CVS : a) Heart : There is increase in heart rate ( positive chronotropic), increased excitability (bathmotropic) and conductivity (dromotropic) of myocardium. All these effects are due to stimulation of beta one receptors. There is increase in cardiac output. b) Blood vessels :- There is constriction of cutaneous and splanchnic vessels (alpha one receptors), Suggestions: facebook.com/asifpatel.ggmc

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162 dilatation of skeletal muscle blood vessels (beta2) and venoconstriction. c) Blood pressure : There is increase in systolic pressure due to increase in force of contraction . Diastolic pressure may rise or fall (due to muscle vasodilatation ). Pulse pressure widens. Mean arterial pressure remains same. Peripheral resistance may be normal or may fall. 2. On Respiratory System: Epinephrine causes relaxation of bronchial smooth muscle and bronchodilatation (beta2).It also increases rate and depth of respiration. 3. On metabolism :- a) There is increase in BMR and rise in body temp b) stimulates glycogenolysis in liver and muscle by increasing activity of phosphorylase (beta2) and therefore increases blood glucose levels. c) There is increased breakdown of fats (lipolysis) and rise in FFA levels in blood (beta 1). d) causes fall in plasma K+ due to entry of K+ into skeletalmuscles (beta 2). 4. On nervous system:- It causes alertness, arousal, restlessness, fatigue, insominia etc. by causing activation of ARAS. Reaction time is reduced. 5. Skeletal muscle:- Increased excitability, contractility increased production of lactic acid. 6. On GIT : Relaxation of smooth muscle of GIT leading to decrease in motility (alpha) and increased tone of sphincters. Secretions of GIT glands become less in quantity, thick and viscid due to vasoconstriction. 7. On Excretory system:- constriction of efferent arteriole, decrease in GFR and urine volume. There is relaxation of detrusor muscle, contraction of sphincter and retention of urine. 8. Other actions.: 9. Stimulates secretion of insulin and glucagon. 10. Dilatation of pupils due to contractions of dilator pupillae and and retraction of eyelids. 11. Contraction of piloerector muscles of skin. 12. In animals, epinephrine causes contraction of smooth muscles in splenic capsule and release of cells into circulation. Action of Norepinephrine: - differ from those of epinephrine in fallowing ways: 1. It causes generalized peripheral vasoconstriction. It therefore increase peripheral resistance and diastolic pressure. 2. It causes reflex bradycardia(through Sino-aortic reflex) due to rise in blood pressure. Hence cardiac output may decrease. 3. Its effects on metabolism, blood sugar and bronchial muscles are less potent than those of epinephrine. Actions of Dopamine : 1. It has positive inotropic effect on heart and increases systolic pressure. 2. Causes generalized vasoconstriction and 3. Renal vasodilatation. 4. Acts as neurotransmitter in nervous system (nigrostriatal pathway). Mechanism of action : actions of epinephrine and norepinephrine are mediated through alpha and beta adrenergic receptors. Alpha receptors are usually excitatory and situated in blood vessels,iris,sphincters of GIT. Beta receptors are excitatory at some places (heart) and inhibitory at other (bronchi, blood vessels), iris, sphincters of GIT. : SHORT NOTES: *Q. FOLLICLE STIMULATING HORMONE (FSH) :It is a glycoprotein hormone secreted by gonadotroph cells of ant. pituitary. Actions : A) In female it is responsible for early growth and maturation of Graffian follicle. 1. It stimulates proliferation of granulosa cells . 2. Promotes conversion of stromal cells of ovary into theca interna and theca externa cells surrounding the follicle. 3. It stimulates secretion of estrogen from granulosa and theca cells by increasing activity of aromatase. 4. It potentiates response to LH by increasing LH receptors on granulosa cells. 5. Also increases synthesis of FSH receptors and increases its own effectiveness. B) In males 1. It acts on sertoli cells of seminiferous tubules and stimulates spermatogenesis, i.e. maturation of spermatids into spermatozoa 2. It also stimulates secretion of inhibin, mullerian regression factor, androgen binding protein etc. from sertoli cells. Regulation of secretion :- FSH secretion is controlled by 1. Negative feedback effect of circulating estrogen levels . Hence FSH level fall upto 10-12 days of ovarian cycle. On 13 th day of cycle estrogens exert a positive feedback effect producing a small FSH surge. 2.Gonadotropin releasing hormone produced by hypothalamus stimulates secretion of FSH. 3. Inhibin produced by sertoli cells (males) or corpus luteum cells inhibits FSH secretion. 4. During pregnancy FSH levels are Suggestions: facebook.com/asifpatel.ggmc

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low due to negative feedback effect of high oestrogens. 5. After menopause FSH levels remain high for some time.

*Q. LEUTEINIZING HORMONE (LH) : It is a glycoprotein hormone secreted by gonadotroph cells of ant pituitary. ACTION: A) In female : 1. It brings about ovulation on 14th day of ovarian cycle. About 9 to 16 hours before ovulation, there is LH surge which increases vascularity of follicle, promotes transudation of fluid into follicle which becomes tense and stimulates theca externa to produce proteolytic enzymes which will bring rupture of follicle and release of ovum. 2. Formation of corpus luteum :- After release of ovum, the rest of Graffian follicle gets converted into corpus luteum. Under the influence of LH, granulosa cells enlarge, develop lipid inclusion (yellow color) and smooth endoplastic reticulum. These changes are called luteinization. 3. LH stimulates lutein cells to secrete large amounts of progesterone and oestrogens which produce secretory change in uterine endometrium. 4. LH maintains corpus luteum for 10-12 days – luteotrophic action. B) In males LH stimulates leydig’s cells of testis to secrete testosterone which is the male sex hormone. Regulation of LH secretion :- 1. Negative feedback effect of circulating oestrogen and progesterone levels :- Rise in levels of these hormones inhibits LH secretion upto 11th day of cycle after which high oestrogen levels exert a positive feedback effect and produce LH surge on 13th day. 2. Hypothalamus (arcuate nucleus) secretes Gonadotropin releasing hormone which promotes release of LH. GnRH secretion is controlled by blood levels of sex hormone and by neural impulses. Applied aspect:- Oral contraceptives contain progesterone which prevents LH surge and therefore ovulation does not occur. *Q. ACROMEGALY : Is a condition resulting from hypersecretion of growth hormone in adults (after fusion of epiphyses) either due to tumor or hyperactivity of somatotropes of ant. Pituitary. Features :- 1. Normal height because epiphyses have already fused. 2. There is enlargement of hands and feet. Fingers and toes become very thick due to enlargement of periosteal bones. 3. Excess growth of lower jaw which protrudes forwards (prognathism). 4. There is enlargement of skull bones, cheek bones and frontal bones (frontal bossing). 5. Enlargement and widening of nose due to excess growth of soft tissue. Tongue is enlarged. 6. Excess growth of supraorbital ridges causing slanting of forehead. All these facial changes produce Gorilla like face. 7. There is enlargement of vertebrae and abnormalities of spine like kyphosis or osteoarthritis. 8. Excess growth of soft tissues, enlarged organs like liver, spleen, heart, GIT etc. 9. Glucose tolerance is reduced. There may be hyperglycemia, but frank diabetes mellitus may not occur. 10. Patient complains of headache due to rise in intracranial pressure. 11. Visual disturbance like bitemporal hemianopia may be seen due to pressure of tumor on central part of optic chiasma. 12. X-ray of skull shows enlargement of sella tursica. 13. Diagnosis is confirmed by increased GH levels and somatomedin levels in plasma. Treatment :- 1. Surgical removal of tumor. 2. Irradiation of tumor.

*Q. GIGANTISM: Is a condition in which is hypersecretion of growth hormone in childhood (before fusion of epiphyses). Hypersecretion can result from 1. Increased activity of somatotroph cells of ant pituitary or 2. Tumor (edema) arising from somatotrophes. Features :- 1. Unusually tall stature (7 to 8 feet) due strong stimulation of growth of epiphyseal cartilage by the action of IGF-I. There is excessive growth spurt. 2. Hand and foot size are increased 3. There are deformities of chest wall and spine abnormalities like kyphosis. Osteoporosis may also be seen.4. There is excess growth of soft tissue leading to thick skin and enlargement of viscera like heart liver, spleen, kidneys, GI tract, tongue etc. 5. There is hyperglycemia which can cause exhaustion of insulin secretion by beta cells of pancreas Suggestions: facebook.com/asifpatel.ggmc

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164 leading to pituitary diabetes mellitus. About 10% giants develop diabetes. 6.There may be headache and visual disturbance like bitemporal hemianopia due to pressure of pituitary tumor on central part of chiasma. 7. X-ray of skull shows enlargement of pituitary fossa. 8. Plasma GH and IGF I levels are increased. 9. If untreated, the tumor can cause destruction of entire pituitary gland producing panhypopituitarism. Treatment :-1.Surgical removal of tumor. 2.Irradition with yttrium 90. 3. Somatostatin 4. Bromocriptine.

*Q. DIABETES INSPIDUS: Is a condition resulting from reduced secretion of Anti Diuretic Hormone by supraopticneurons, which may be due to 1. Trauma to hypothalamus (head injury, neurosurgery). 2. Tumors (primary or secondary). 3. Thrombosis of blood vessels supplying hypothalamus Features: 1. Polyuria: Passing of large volume of urine from 5 to 15 lit/ day. (Diuresis). It is due to lack of ADH leading to failure of water reabsorption from collecting ducts. 2. Intense thirst and drinking of large quantities of fluid (Polydypsia) to compensate for water lost in urine. 3. Urine is very dilute. It has specific gravity of 1.003 to 1.005 and urine osmolality is less than 100 mosmol/kg. 4. serum Na+ conc. is moderately increased but remains less than 150 mmol/lit. 5. Risk of dehydration.- If water is not accessible, there is a risk of fatal dehydration. 6. Water deprivation test fails to increase osmolarity of urine. Treatment : It is treated with an synthetic analogue of ADH called desamino-D-arginine vasopressin(DDAVP). 2. Chlorpropamide which enhances renal response to ADH. 3. Administration of synthetic ADH suspenced in oil. 4. Plenty of water. Nephrogenic diabetes insipidus :- is a condition in which kidneys fail to respond to circulating ADH due to lack of V2 receptors. It is an X chromosome linked genetic disorder seen only in males.

*Q. OXYTOCIN: Is a peptide hormone secreted by neurons of paraventricular (mainly) and supraoptic nuclei of hypothalamus. ACTIONS :- 1. Milk ejection reflex (milk letdown) :- Normally in lactating woman, milk secretion is a continuous process but secreted milk does not flow spontaneously into the ducts, a process which occurs only at the time of suckling by the action of oxytocin. Suckling is major stimulus for oxytocin secretion. During this process, touch receptors in nipple and areola are stimulated and afferent impulses are carried into Sp. cord to periventricular nuclei of hypothalamus. Thus oxytocin is released from nerve ending in post. pituitary and through the circulation reaches the breasts where it acts on myoepithelial cells surrounding the alveoli causing their contraction. Thus milk is squeezed into the ducts at a pressure of 10-20 mm of Hg and is made available to the baby. This is called milk ejection reflex which is a neuroendocrine reflex. 2.Oxytocin causes contractions of uterus at the time of delivery forcing the baby down into the cervix. This causes stretching of cervix, stimulation of stretch receptors and afferent impulses pass into hypothalamus stimulating oxytocin release which further increase uterine contractions in a positive feedback manner leading to expulsion of fetus. 3. After delivery of baby and placenta it maintains uterus in a sustained contracted state and stops bleeding. 4. Oxytocin also increases contractility of uterus in non-pregnant state. 5. In males it causes contraction of myoepithelial cells of seminiferous tubules. 6. Some animals it causes contraction of smooth muscles of seminal vesicle 7. It may act as neurotransmitter. Stimuli for Secretion are 1. Suckling 2.Distension of cervix 3.Genital stimulation 4.Emotional stress.

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*Q. SYNTHESIS OF THYROID HORMONES:Thyroid hormones are 3,5,3',5' Tetraiodothyronine or Thyroxine (T4) and 3, 5, 3' Triodothyronine (T3) . They are synthesized by the thyroid cells inside a large glycoprotein molecule called Thyroglobulin containing the tyrosine residues. Steps involved in synthesis are 1. Iodine trapping or Iodide pump: Iodide that is absorbed from GIT enters the circulation and reaches thyroid gland. It is then actively transport from ECF into the cells by a protein called Iodide pump situated on the basal surface of these cells. Iodide pump transports iodide against electrochemical gradient and can concentrate it upto 200 times. 2. Oxidation of Iodide :- Iodide is then oxidized to Iodine by the action of enzyme peroxidase and in pressure of H2O2 which accepts the electrons. 3. Iodination of tyrosine or organification :- Is the process of attachment of iodine to the tyrosine molecules inside thyroglobulin brought about by iodinase. First the iodine combines with position 3 of tyrosine forming monoiodotyrosine(MIT) and then second iodine attaches at position 5 to from Diiodotyrosines (DIT) 4. Coupling: In this, 2 DIT molecules undergo oxidative condensation to from T4 or one MIT condense with one DIT to form T3. Small amounts of reverse T3(3, 3’, 5’ T3 ) are also formed. Coupling occurs within the thyroglobulin molecule which is then stored in the colloid. Stored thyroid hormones can last for 2-3 months. Release of thyroid hormones :The apical processes of thyroid cells ingest a small quantity of colloid forming pinocytic vesicle and the thyroglobulin in it is digested by lysosomes releasing T3 and T4. Synthesis of thyroid hormone is regulated by TSH which stimulates iodide pump, organification and coupling. HYPERTHYROIDISM :Also called thyrotoxicosis results form hypersecretion of thyroid hormones due to 1. Formation of thyroid stimulating antibodies (of autoimmune origin) which combine with TSH receptors on thyroid cells and activate them (Grave’s disease). 2. Toxic adenoma or adenocarcinoma of thyroid gland. Features :- 1. Condition is seen more commonly in women in 3rd and 4th decade of life. 2. Rise in BMR 60 to 100% above normal increased body temp, excessive sweating and intolerance to heat. All these effects are due to calorigenic action of excess thyroid hormones. 3. Exophthalmos :protrusion of eye balls wide palpebral fissure, dryness and infections of cornea and conjunctiva and paralysis of ocular muscles due to degenerative swelling of ocular muscles by autoantibodies. 4. Loss of weight inspite of good appetite and food intake, increased GI motility can produce diarrhea. 5. CVS:- tachycardia, palpitation, increase in cardiac output, decrease in peripheral resistance, hyperdynamic circulation and cardiac arrhythmias. High output failure may occur. 6. Skin is warm (vasodilatation and moist). 7. CNS :-Restlessness, irritability, extreme fatigue, insomnia, anxiety and brisk reflexes. 8. Muscles : Excessive breakdown of muscle proteins (myopathy) leading to fine tumors, weakness and wasting of muscles. 9. Skeleton shows osteoporotic changes. 10. Thyroid gland is enlarged (Goitre) 11. Vitamin deficiencies may develop. Blood shows increase in glucose, Ca+ and FFA levels and fall in cholesterol, phospholipid and TSH levels. 13.Liver glycogen is reduced . 14. There may be menstrual disturbances. 15. Thyroid storm :- excess sweating, dehydration, shock, high fever arrhythmias. Diagnosis is confirmed by 1. High T3 and T4 levels(RIA). 2. Low TSH levels 3. High I131 uptake. Treatment :- 1. Antithyroid thiourea compounds like carbimazole. 2. Surgery partial thyroidectomy. 3. Radio iodine therapy 4. Beta blockers to reduce symptoms. *Q. CRETINISM : It’s a condition due to decreased secretion of thyroid hormones in infancy and childhood. It can result from 1.congenital absence of thyroid. 2. Genetic defects in enzymes concerned with thyroid hormone synthesis. 3. Lack of iodine in diet of child or mother (during pregnancy). 4. Pituitary or hypothalamic diseases affecting TSH and TRH secretion. Suggestions: facebook.com/asifpatel.ggmc

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166 Features :- 1. Retardation of physical growth leading to dwarfism. It is due to loss of growth promoting action of thyroid hormones. On skeleton as well as soft tissues. Involuntary movements are sluggish. 2. Mental retardation due to failure of neural growth. I.Q. is less. Developmental milestones like sitting, standing, walking, eruption to teeth are all delayed. There may be neurological defects like deaf mutism, spasticity and motor impairment. 3. Retardation of sexual growth and delayed onset of puberty. 4. Child has idiotic bloated face, thick lips, enlarged protruding tongue and dribbling of saliva. 5. Abdomen is protuberant (pot belly)and umbilicus is everted. These changes due to less retardation of soft tissue growth as compared to skeletal growth 6. BMR is reduced. Body temp is less and there is intolerance to cold. 7. Appetite is reduced GI motility is less and constipation is frequent. 8. Skin is coarse and dry and may show yellowish pigmentation due to carotinemia. 9. Dry hair. 10. X-ray of bones show stippling of epiphyses. Diagnosis :- 1. Decrease in T3, T4 levels (RIA). 2. TSH levels increased. 3. BMR reduced. Treatment :- 1) administration of thyroxine tablets. 2. Iodine supplemention in diet.

*Q. MYXOEDEMA :Is a condition characterized by hyposecretion of thyroid hormones in adults. Causes :- 1. Deficiency of Iodine in the diet leading to reduced synthesis of thyroid hormones. 2. Autoimmune disease formation of antibodies against thyroid tissue and thyroglobulin - Hashimoto's thyroiditis. 3. Use of excess antithyroid drugs like propylthiouracil. 4. As a complication of surgery or irradiation of thyroid glands in treatment of hyperthyroidism. 5. Goitrogenic substances in diet. 6. Hypothalamic or pituitary failure. Features :- 1. Seen more commonly in females. 2. The entire body and specifically the face has a puffy oedematous look due to deposition of myxomatous tissue under the skin which is normally removed by thyroid hormones. 3. CVS :-Bradycardia, decrease in cardiac output, prolonged circulation time, low voltage QRS complexes. There is hypercholesterolemia predisposing to atherosclerosis, angina and infarction. 4. CNS :- Lethargy, mental and muscular sluggishness, somnolence, fatigue, loss of memory and sometimes psychosis. Reflexes are sluggish. 5. Decrease in BMR by 40% to 50%, low body temp and intolerance to cold. 6. Enlargement of tongue, hoarse or gruffy voice, slow slurring type of speech due to deposition of myxomatous tissue in tongue and larynx. 7. Skin becomes coarse, dry, loss of hair from eyebrows, carotinemia (yellow skin) may occur. 8. GIT :- appetite is reduced, weight gain occurs, distension of abdomen, constipation. 9. Hypoglycemia. 10. Menstrual cycle disturbances. 11. Effusion into pericardial, pleural, peritoneal or joint cavities. 12. Deafness due to fluid in middle ear may be seen. Diagnosis :- 1. Low T4, T3 levels. 2.High TSH levels. 3. High radioiodine uptake. Treatment :- 1.thyroxide tablets 2. Iodine in diet. *Q. TETANY (HYPOPARATHYROIDISM) Is a clinical condition characterized by sustained cortraction (spasm) of muscles due to lowering of serum Ca+ levels. Causes: 1. hyperparathyroidism which can occur as a complication of surgery on thyroid or larynx or as autoimmune disease due to formation of autoantibodies against parathyroid cells. PTH secretion falls therefore serum Ca+ falls. 2. Rickets (Vit. D deficiency) 3. Intestinal sprue. 4. Chronic renal failure. These conditions reduce Ca+ absorption from GIT or renal tubules. 5. Alkalosis also precipitates hypocalcaemic tetany. Pathophysiology:- Normally Ca+ ions maintain the normal level of excitability of nerves and muscle by controlling permeability of Na+ channels [Ca has inhibitory effect on Na channels, decrease in Ca+ ions causes increased permeability of Na+ ions and this partially depolarises the membrane]. When Ca+ level falls, this functions is lost, nerves and muscles become hyperexcitable and spontaneously initiate impulses leading to spasm. Suggestions: facebook.com/asifpatel.ggmc

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Clinical Features:- 1. Carpopedal spasm :-is due to spasm of flexor muscles of hand producing flexion at wrist and metatarsophalangeal joints. Fingers are extended and thumb is flexed towards palm. Also called Accoucheur’s hands. 2. Trousseaus’ sign:- same as above but is elicited by tying sphygmomanometer cuff. 3. Laryngeal stridor:- crowing inspiratory sound due to spasm of laryngeal muscles. A strong spasm of vocal cord can cause asphyxia and death. 4. Chvostek’s sign :Tapping the factor nerve the angle of jaw caused spasm of ipsilateral facial muscles. 5. Erb’s sign:increased excitability of nerves to galvanic current. 6. Generation convulsions may occur due to lowering of threshold of epileptic focus. These symptoms are precipitated by exercise. Treatment:1. Prompt IV administration of calcium gluconate 2.High Vit D and Ca+ in diet.

*Q. GLUCAGON :Is a peptide hormone secreted by 1.Alpha cells of islets of Pancreas 2. Duodenal mucosae (enteric glucagon). Physiological actions :- 1. It stimulates glycogenolysis in liver cells by activating the enzyme phosphorylase via cyclic AMP mechanism and promotes release of glucose into circulation.2. Stimulates gluconeogenesis in liver by conversion of pyruvate into phosphoenol pyruvate and by increasing activity of transaminases and deaminases. Also increase entry of amino acids into the liver cells. 3. By above actions, it increases blood glucose levels (hyperglycemia) 4. It promotes lipolysis in adipose cells by activating hormones sensitive lipase and increase FFA levels in plasma. 5. Ketogenic effect Glucagon increases production of acetyl COA (by increasing oxidation of fatty acids) which condense to from ketone bodies. 6. It increases force of contraction of myocardium (positive inotropic action). 7. Stimulates secretion of growth hormone and that of insulin and Somatostatin by paracrine actions. 8. Stimulates bile secretion 9. Inhibits gastric acid and pancreatic secretion. Regulation:- 1. Blood glucose level :- Fall stimulates and rise inhibits glucagon secretion It thus regulates blood glucose levels. 2. Increase in amino acid levels (esp. arginine) following meals stimulates glucagon secretion and prevents hypoglycemia from Action of insulin. 3. Exercise stimulates glucagon secretion which prevents hypoglycemia during exercise. 4. GI hormones like Gastrin and CCK stimulate glucagon secretion. Secretin inhibits. 5. Insulin and somatostatin inhibits glucagon secretion by Paracrine effect.

PATHOPHYSIOLOGY OF DIABETES MELLITUS :- It a hereditary disorder resulting from relative or absolute deficiency of insulin precipitated by obesity, viral infection or autoimmune process affecting pancreas. A) Derangement in Carbohydrate Metabolism :- 1. Decreased entry of glucose into most body cells and decreased utilization of glucose. 2. Increased release of glucose into the circulation by a) increased glycogenolysis b) increased neoglucogenesis. 3. Increase in blood glucose levels (hyperglycemia) sometimes upto 700-800 mg %. 4. There is intracellular glucose deficiency. 5.Hyperglycemia increases osmolarity of blood leading to intense thirst and water intake (polydypsia) 6. Hyperglycemia also causes osmotic diuresis (polyuria) and dehydration can occur. 7. Intracellular glucose deficiency fails to activate satiety centre leading to excess food intake (polyphagia). 8. Glucose tolerance is reduced. B) Derangements of fat metabolism :- 1. There is increased mobilization of fats (lipolysis) due to activity of hormone sensitive lipase which is normally suppressed by insulin. FFA levels rise. 2. Increased breakdown of fatty acids due to non availability of glucose in the cells leads to increased formation of acetyl CoA units which are converted in the liver cells to acetoacetic acid, beta hydroxybutyric acid and acetone. These ketone bodies accumulate in blood (ketosis) and produce acidosis and coma. 3. Ketoacidosis stimulates respiration - Kussmaul breathing. 4. Ketone bodies Suggestions: facebook.com/asifpatel.ggmc

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168 are excreted in urine (Ketonuria) and with them electrolytes like Na+ are lost leading to Na+ depletion. 5. Blood cholesterol levels may increase predisposing to atherosclerosis. C) Protein metabolism :- 1. Increased breakdown of protein leading to increased AA levels. 2. There is increased breakdown of amino acids for energy production and for neoglucogenesis. 3. Protein sythesis is reduced. All these factors lead to cellular protein depletion, muscle wasting and retardation of growth in diabetic children. PRIMARY HYPERALDOSTERONISM or Conn's syndrome : is due to excess secretion of aldosterone in conditions like adrenal adenoma or hyperplasia of zona glomerulosa. Features :- 1. Hypokalemia is the most characteristic feature. Excess aldosterone causes increased K+ secretion and loss of K+ from the body (K+ depletion). 2. Hypokalemia depresses transmission of action potentials along nerve and causes extreme weakness and transient periods of muscular paralysis. 3. Prolonged K+ depletion also damages kidney. Its concentration function is lost leading to polyuria. 4. Excretion of H+ ions by kidney is increased leading to metabolic alkalosis which can precipitate tetany. Urine becomes more acidic. 5. There is slight retention of Na+ ions and increase in plasma Na++. ECF volume also increases, but frank edema does not occur due to aldosterone ascape. 6. There is mild hypertension due to Na+ retention and rise in ECF volume. 7. Plasma renin levels are low due to negative feedback effect of excess aldosterone. Treatment :- 1. Surgical removal of adenoma. 2. Diuretics like spironolactone. Secondary hyperaldosteronism :- Here, hypersecretion of aldosterone is secondary to excess renin. It is seen in conditions like congestive cardiac failure, renin secreting tumor of kidney, cirrhosis of liver and nephrotic syndrome which either decrease renal blood flow stimulating renin secretion from JG cells or decrease inactivation of renin. Excess renin then forms angiotensin II which stimulates glomerulosa cells to produce more aldosterone. Features are same as those of primary, but renin levels are high. Treatment :- 1. Treatment of cause. 2. Spironolactone.

*Q. CUSHING’S SYNDROME ( Hyperadrenalism) Named after Harvey Cushing. Results from hypersecretion of cortisol. Causes :- 1. Cortisol secreting tumor (adrenal adenoma) 2. ACTH secreting tumor of corticotropes of ant pituitary (basophil adenoma) 3. Ectopic ACTH secreting tumors like lung cancer, pheochromocytoma etc. 4. Excess clinical administration of cortisol (iatrogenic). Features :- 1. Redistribution of body fat with central obesity. Fat is mobilized from limbs and deposited in face (moon face) upper back (buffalo hump) and in abdominal wall. Fat deposition in abd wall causes stretching and rupture of collagen fibres producing purple striae on abd wall. 2. There is excess protein catabolism in the body except liver cells. Loss of proteins from muscles causes severe weakness and wasting of proximal limb muscles. 3. Skin and subcutaneous tissues become thin. 4. There is lymphopenia and suppression of immune response. Wound healing is poor and person becomes more susceptible to infection. 5. There is hyperglycemia (due to increased neoglucogenesis and decreased peripheral utilization) which can lead to exhaustion of insulin secretion and adrenal diabetes mellitus. 6. There is excess mobilization of bone matrix leading to hyperacalcemia, calciuria, oesteoporotic changes and multiple fractures. There is hypertension due to retention of Na and water (mineralocorticoid effect of excess cortisol) Mild edema may appear. 8. There may be mental depression and psychosis. 9. Peptic ulceration, 10. Acne and hirsutism due to excess androgens. Treatment:- 1. Surgical removal of tumor. 2. Irradiation of tumor. 3. Partial adrenalectomy. 4. Metapyrone which inhibits synthesis of steroid hormones. Suggestions: facebook.com/asifpatel.ggmc

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*Q. ADDISON'S DISEASE :Named after Thoman Addison, it is a condition resulting from hyposecretion of cortisol. Causes :- 1. Autoimmune Origin due to formation of autoantibodies against adrenocortical cells. 2. Tuberculosis of adrenal cortex. 3. Tumors of adrenal cortex which destroy it (adenocarcinoma) 4. Decreased ACTH secretion from ant. pituitary. 5. Congenital enzymatic defects. Features :- 1. Pigmentation of skin and mucus membranes. Loss of negative feedback effect of cortisol leads to excess ACTH secretion which stimulates melanocytes causing deposition of melanin over lips, nipples, skin creases, pressure points and vocal mucosa.2. Frequent attacks of dizziness and fainting due to hypoglycemia in fasting state. Mobilization of proteins and fats is reduced. 3. There is inability to tolerate stress and infection 4. Associated mineralocorticoid deficiency causes hypotension esp. postural hypotension, Na depletion and K+ retention in the body. (Hyperkalemia) 5. There is decreased vascular responsiveness to circulating catecholamines 6. Personality changes like irritability and depression may be seen. 7. Increase in neutrophil and eosinophil count. 8. Hypochlorhydria may occur. 9. Addisonian crisis is precipitated by stress conditions. There is high fever, tachycardia, cramps postural dizziness, vomiting, abdominal pain, Na+ depletion and dehydration. Blood urea increases. Treatment: 1. Administration of small daily doses of cortisol or hydrocortisone 2. Supplemented with mineralocorticoid therapy. 3. IV fluids and correction of electrolyte imbalance. Q. HYPERPARATHYROIDISM :Is a condition in which there is excess secretion of parathyroid hormone (PTH). Causes: 1. Adenoma of parathyroid chief cells 2. Carcinoma. Secondary hyperparathyroidism can occur in 3. Vit. D deficiency 4. Dietary Ca+ deficiency. 5. Chronic renal failure. Features :- 1. Seen more commonly in females. 2. There is increased osteoclastic activity leading to excess bone reabsorption and osteoporosis. Bones develop large multiple cavities called Bone cysts. This condition is called osteitis fibrosa cystica. A slight trauma causes multiple fractures of bones. 3. XRay of hand shows subperiosteal erosions in phalanges. 4. Serum Ca+ levels are increased (hypercalcemia)which produces depression of central and peripheral nervous system, muscular weakness and constipation. 5.Hypercalcemia reduces renal response to ADH, producing thirst and polyuria. 6. Hypercalciuria and increased incidence of renal calculi. 7. There is hypophosphatemia due to increased excretion of phosphates. 8. Prolonged hypercalcemia causes metastatic calcification that is, Ca+ deposition in kidney tubules (nephrocalcinosis), lungs, stomach and walls of arteries throughout the body. 9. There may be hypertension and shortening of QT interval. Treatment: 1. Surgical removal of tumor 2. Treatment of cause in secondary hyperparathyroidism. *Q. CALCITONIN (THYROCALCITONIN) : Is a peptide hormone secreted by parafollicular or C cells of thyroid gland. ACTIONS :- Its principal action is that it lowers plasma Ca+ levels. Hence called Calcitonin. this action is seen within minutes but does not last for a long time. It lowers serum Ca+ by: 1. Inhibition of bone reabsorption and Ca+ release: Calcitonin combines with receptors on osteoclasts and inhibits their activity via cyclic AMP mechanism. Thus bone reabsorption is inhibited. It also decreases the permeability of osteocytic membrane (osteocytes and osteoblasts) to Ca+ levels. Hence Ca+ lowering action of calcitonin depends on rate of bone turn over. It is seen maximally in children and weakly in adults. 2. It suppresses formation of new osteoclasts a long term effect 3. It decreases Ca+ excretion. 4. Decreases Ca+ absorption from intestine, 5. Decreased PO4 reabsorption and causes decreased in blood phosphate levels. 6. Also acts as neurotransmitter. Regulation :- 1. Plasma Ca+ is the major stimulus, slight increase in plasma Ca+ increases calcitonin secretion 3 to 6 times. It thus plays important role in Ca+ homeostasis. 2. GI hormones like Gastrin Suggestions: facebook.com/asifpatel.ggmc

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170 and CCK stimulate calcitonin secretion which then prevents hypercalcemia after meals. 3. Other hormones like glucagon, epinephrine, dopamine etc. stimulate calcitonin secretion. Applied physiology :- Calcitonin is used therapeutically in Pagets disease which results from increased activity of osteoclasts.

*Q. SOMATOSTATIN : Is a peptide hormone containing 14 amino acids secreted by 1. Delta cells of islets of pancreas . 2 . intestinal mucosa . 3. Hypothalamus . Also found in retina and substantia gelatinosa . ACTION:- 1. Somatostatin diffuses to adjacent alpha, beta and p p cells and inhibits secretion of glucagon, insulin and pancreatic polypeptide by its paracrine effect. It thus limits insulin and glucagon response to meals. 2. It reduces motility of GIT, especially of stomach, duodenum and gall bladder. Thus gastric emptying is slowed. 3. It inhibits secretion of HCl, pepsin, intestinal juices and pancreatic secretion. 4. It decreases absorption of glucose and triglycerides from intestine. 5. It inhibits GI Hormones like gastrin, secretin, GIP, VIP and motilin. The overall action is that it prolongs the process of digestion and absorption and maintains a balance between the rate of nutrient absorption and utilization by liver and peripheral tissues. 6. It also acts on somatotrophes of ant. pituitary and suppresses release of growth hormone. 7 . Acts as neurotransmitter in nervous system. Stimuli for secretion of somatostatin: 1. Increased blood glucose levels. 2. Increased amino acid levels aspargine and leucine . 3. Increased FFA levels. 4. GI hormones like CCK, glucagon. 5. Parasympathetic stimulation. Somatostatin secretion is inhibited by insulin and alpha adrenergic transmitters . *Q. MECHANISMS OF HORMONE ACTION:Hormones act in 3 ways to modify cell function. 1. By activation of cellular enzymes :- Here, the hormone combines with the receptor on target cell surface which is a transmembrane protein. HR combination then activates A. Adenylcyclase leading to formation of cyclic AMP which is responsible for action of hormone on the cell like activation of protein kinase, change of memberane permeability ect. Here cAMP acts Second messenger. Examples of hormones acting in this way are TSH, ACTH, PTH etc. B. Phospholipase C which acts on phospholipids and forms Inositol Tri Phosphate and Diacyl glycerol which act as second messengers. They increase intracellular Ca+ which produces effects of hormone. Example: Action of ADH on vascular smooth muscle, TRH on thyrotropesetc . In this mechanism, the action of hormone is seen in few minutes. 2. By Activation of genes : Here, the hormone enters the target cell and combines with receptor protein in cytoplasm (or in nucleus as in case of thyroid hormones). The HR complex then enters the nucleus, combines with specific site on DNA and stimulates transcription to form mRNA. This mRNA diffuses out into cytoplasm where it is translated by ribosomes to form new proteins (esp. enzymes) which produce effects of the hormones on the cell. Examples: steroid hormones like aldosterone, cortisol, testosterone etc. This mechanism has a latent period of 45 minutes to few hours, since it involves synthesis of new proteins. 3. By changing membrane permeability : Certain hormones like acetyl choline, CCK, epinephrine etc. combine with receptors on target cell leading to change in membrane permeability to certain ions like Ca+, k+, Na+ etc. Ca+ ions combine with calmodulin to form Ca+ calmodulin complex which acts as second messenger and produces hormone action like exocytosis of secretion granules, contraction of smooth muscle etc .

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*Q. ADRENAL ANDROGENS:Cells of zona reticularis and zona fasiculata secrete 2 androgenic hormones. They are 1.Dehydroepiandrosterone( DHEA ) and 2. Androstenedion. They are secreted in males as well as females . Physiological actions :- 1. They are responsible for growth and sustenance of pubic and axillary hair. 2. They exert masculinizing effects, but these effects are very weak. In peripheral tissues adrenal androgens get converted into testosterone and produce their effects. 3. They also promote growth due to their protein anabolic action. 4. They increase thickness of sebaceous secretion and predispose to acne. 5. Androgens secreted by adrenals in childhood. 6. They are also responsible for libido i.e. sex desire. Mechanism of action : They act at nuclear level, stimulate transcription and translation to form new proteins. Regulation : Secretion of adrenal androgens is regulated by ACTH. Applied Aspect: Hypersecretion of androgens in prepubertal and adult females produces a condition called Adrenogenital syndrome characterized by growth of beard and moustaches (hirsutism), temporal recession of hair, atrophy of breasts, enlargement of clitoris, amenorrhoea, heavy and hairy arms and legs. Hypersecretion in female fetus before 12th week of gestation causes formation of male type of external genitals, a condition called female pseudohermaphroditism. Hypersecretion in a male child causes precocious puberty.

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REPRODUCTIVE SYSTEM

Chapter 11

*Q. DESCRIBE THE PROCESS OF SPERMATOGENESIS & FACTORS AFFECTING IT. Spermatogenesis is the process of formation of spermatozoa from primitive germ cells called spermatogonia. The process takes place in seminiferous tubules of testis, starting at puberty and continues upto old age. Stages of spermatogenesis:- The seminiferous tubules are lined by 2 to 3 layers of germinal epithelial cells called spermatogonia type A. These cells divide 4 times and differentiate to form 16 cells spermatogonia type B which migrate among sertoli cells undergo enlargement and maturation to form large cells called primary spermatocytes. Each primary spermatocytes contains diploid number of chromosomes arranged in 23 pairs. It then undergoes first meiotic division (in which there is separation of chromosomes from the pair) to form secondary spermatocytes containing haploid number(23) of chromosomes. Each secondary spermatocyte then divides (second meiotic division in which chromatids separate) to form two cells called spermatids, also containing 23 chromosomes. The spermatids then undergo maturation to form spermatozoa. This process of maturation is called spermiogenesis and occurs inside the sertoli cells. Change taking place in spermatid are 1. Loss of much of the cytoplasm. 2. Nucleus condenses to form head of spermatozoa. 3. Golgi apparatus condenses to form acrosomal cap 4. Cell elongates to form tail of spermatozoa. The fully developed spermatozoan is 65 to 70 microns in length, has a fattened oval head and an elongated tail consisting of body, main piece and end piece. Such fully developed sperms are released into the lumen of seminiferous tubules and then pass in to epididymis where they undergo maturation and become capable of fertilization (spermeation). The whole process of spermatogenesis takes about 74 days.(Rut cycle). Role of sertoli cells : 1. They maintain the activity of spermatocytes and promote maturation of spermatid in to spermatozoa. 2. They secrete nutritious fluid into the SF tubule for the sperms. 3. They secrete mullerian inhibition factor, oestrogens, inhibin and androgen binding proteins. 4. They also form blood testis barrier. FACTORS AFFECTING SPERMATOGENESIS: A. HORMONES :- 1. Follicle stimulating hormone (FSH) produced by ant. pituitary acts on sertoli cells and facilitates maturation of spermatids. Sertoli cells, in turn, produce a hormone called inhibin which has a negative feedback effect on FSH Suggestions: facebook.com/asifpatel.ggmc

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secretion. Thus spermatogenesis is regulated by interaction between FSH and inhibin. 2. Testosterone :- is essential for spermatogenesis particularly, it stimulates division of primary spermatocytes. 3. Luteinizing Hormone (LH):- stimulates spermatogenesis indirectly by stimulating testosterone secretion by Leydig cells. 4. Oestrogens produced by Sertoli cells stimulate spermiogenesis. 5. Growth hormone is essential for spermatogenesis . It stimulates early division of spermatogonia and maintains metabolic functions of testis. B. TEMPERATURE : Spermatogenesis requires a temperature 2° to 5° C less than abdominal temperature. It is maintained at low temp by: 1. Dartos muscle. 2. Sweat glands in scrotum. 3. Vascular arrangement (counter current). Applied aspects:- 1. Undescended testis even after puberty is associated with absence of spermatogenesis. 2. Irradiation of testis by X rays of other rays causes destruction of germ cells and inhibits spermatogenesis. 3. Infections of testis by viruses like mumps also inhibits spermatogenesis leading to oligospermia or azoospermia.

*Q. DESCRIBE THE PHYSIOLOGICAL ACTIONS AND REGULATION OF TESTOSTERONE (OR MALE SEX HORMONES OR ANDROGENS) SECRETION: Testosterone, Dehydroepiandrosterone and Androstenedione are the androgens secreted by Leydig cells of the testis, the latter two are also secreted by zona reticularis of adrenal cortex. PHYSIOLOGICAL ACTIONS :- A ) In fetal life :- 1. Sex differentiation : - Testosterone secreted by genital ridge and later by fetal testis is responsible for formation of male genitals like penis and scrotum in male fetus. It also cause disappearance of Mullerian duct system. 2. Descent of Testis : Testosterone secreted by fetal testis is responsible for descend of testis into scrotum in late fetal life. B) At the time of puberty :3. Growth of external genitals and accessory sex organs:- Androgens cause increase in the size of penis and scrotum. They also cause enlargement of seminal vesicles, prostate, epididymis and vas deferens. 4. Development of male secondary sexual characters like. a) Growth of beard and moustaches, pubic hair extending along linea alba upto umbilicus, growth of hair on chest and axilla etc. They also cause temporal recession of hairline and predisposes to baldness. b) development of typical hoarse, low pitched, masculine voice due to enlargement of larynx and hypertrophy of laryngeal mucosa . c) male emotional pattern like aggressiveness, interest in female sex etc. 5. Skeletal growth : Androgens are responsible for the growth spurt that occurs at puberty but they also promote rapid fusion of epiphyses with the shafts of long bones, thus stopping skeletal growth. Androgens also cause widening of shoulders, pelvis becomes narrow and funnel shaped . C) In adult life: 6. Androgens stimulate spermatogenesis especially, division of primary into secondary spermatocytes and Suggestions: facebook.com/asifpatel.ggmc

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174 motility of sperm. 7. Protein anabolic action : androgens promotes synthesis of proteins and positive nitrogen balance. They also cause hypertrophy of muscles characteristically seen in males. 8. Androgens increase Basal Metabolic Rate due to their protein anabolic effect causing synthesis of more enzymes. 9. Skin becomes thick and there is excess secretion of sebaceous glands predisposing to acne. 10 . Testosterone stimulates production of erythropoietin and is responsible for greater RBC count in males. 11 . It also causes retention of Na+, Ca+ and water in the body . Mechanism of action :- In some target cells, testosterone is converted into DiHydrotestosterone which combines with cytoplasmic receptor protein, enters the nucleus and stimulates transcription and translation to form new proteins which exert the effect of the hormone. REGULATION :- 1. Luteinizing Hormone secreted by ant. pituitary stimulates testosterone secretion by Leydig cells. 2. Luteinizing Hormone Releasing Hormone secreted by hypothalamus promotes release of LH and thus stimulates testosterone secretion 3. Negative feedback control :- High blood levels of testosterone exert a negative feedback effect on secretion of LHRH and also that of LH. Thus gonadotropins control testosterone secretion. 4.Prolactin : potentiates the actions of LH on Leydig cells and stimulates testosterone secretion . 5. In fetal life Human chorionic gonadotropin ( HCG ) also stimulates secretion of testosterone. Applied aspects :- Hypersecretion of testosterone in childhood causes precocious puberty while hypersecretion at puberty causes male eunuchism.

*Q. DESCRIBE THE HORMONAL CONTROL OF MENSTRUAL CYCLE :Menstrual cycle is the cyclical change taking place in uterine endometrium in the reproductive life of a woman, the average duration of cycle being 28 days . 1 . Control of proliferative phase of menstrual cycle :At the beginning of this phase which lasts from 5th to 14th day of the cycle, FSH secretion by ant. pituitary is increased causing rise in FSH levels and a small rise in LH levels. This rise is due to low blood levels of oestrogen and progesterone which normally exert negative feedback effect on FSH and LH. Increased FSH acts on granulosa cells of ovary and causes growth and maturation of ovarian follicle. These granulosa cells start secreting oestrogens and the blood oestrogen levels rise to a peak (primary peak) on 12th to 13th day of cycle. Oestrogens act on uterine endometrium and produce changes like proliferation of endometrial glands, stromal cells, blood vessels, re-epithelialization and increase in thickness of endometrium. Increased oestrogen levels exert a negative feedback effect on FSH and LH, hence blood levels of these hormones start falling. 2. Control of ovulation:- After 12th day of cycle, high oestrogen levels exert a positive feedback effect on LH and FSH secretion, producing a high LH surge (and a small FSH surge). LH surge is responsible for ovulation and for formation of corpus luteum. 3. Control of secretary phase :- Lasts from 15th to 28th day of cycle. In the initial part of this phase, LH secretion is fairly high and sustains corpus luteum for 10-12 days. The cells of corpus luteum start secreting large quantities of progesterone and lesser quantities of estrogens producing a high peak in progesterone level and a smaller (secondary) peak in oestrogen levels. Progesterone and oestrogens are responsible for secretary phase of endometrial cycle which is characterized by turtuosity and secretary changes in endometrial glands, (they start secreting fluid called uterine milk) deposition of nutrients in stromal cells, further increase in vascularity and thickness of endometrium. Suggestions: facebook.com/asifpatel.ggmc

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Increased levels of oestrogens, progesterone and inhibin exert a strong negative feedback effect on FSH and LH secretion. Thus FSH and LH level fall to a low value causing degeneration of corpus luteum on 26th day of cycle, involution of corpus luteum causes decrease in levels of oestrogens and progesterone towards the end of this phase. 4. Control of menstrual phase :- The phase lasts from first to fourth day of the cycle and results from sudden withdrawal of oestrogens and progesterone. Lack of hormonal support as well as constriction of spiral arterial causes necrosis and sloughing out of superficial two thirds of endometrium. Few ml of blood and unfertilized ovum is also lost along with endometrium. In this phase the FSH and LH levels start rising again due to lack of negative feedback effect of oestrogens and progesterone. At the end of menstrual phase, proliferative phase begins and the hormonal changes are repeated in the same sequence. Applied Aspects :-Hyposecretion of ovarian hormones (hypogonadism) causes abnormalities of menstrual cycles or total amenorrhoea. During pregnancy, FSH, LH levels are low (due to negative feedback of high estrogens and progesterone) causing stoppage of menstrual cycles. *Q. DESCRIBE THE OVARIAN CYCLE AND ITS HORMONAL CONTROL: The cyclical changes taking place in ovary during reproductive life of a female are called ovarian cycle (Duration- 28 days). Phases of ovarian cycle are :Follicular phase :- In which there is growth and maturation of ovarian follicles. It lasts from 1st to 14th day of the cycle. In the ovary, there are large number of primordial follicles consisting of primary oocyte surrounded by a layer of granulosa cells. About 6 to 10 such follicles then mature to form primary follicles with enlarged ovum surrounded by 2-3 layers of cuboidal granulosa cells, however after 6th day of cycle only one follicle grows further, others regress. In this follicle, granulosa cells proliferate and secrete zona pellucida around ovum. Surrounding stromal cells of ovary condense around the granulosa cells forming theca interna and externa. Granulosa cells start secreting liquor folliculi containing high conc. of oestrogens and a cavity appears in the follicle (Antral follicle), thus at the end of this phase, a mature Graafian follicle is formed, 1 to 1.5 cm in size, consisting of ovum surrounded by cumulus oophorus lying at one pole and a large antrum filled with liquor. Hormonal control :- All these changes are due to FSH (mainly) and LH secreted by ant pituitary. FSH stimulates proliferation of granulosa cells as well as theca cells. It also stimulates oestrogen secretion by granulosa cells. It increases its own effectiveness and that of LH by increasing the number of FSH and LH receptors on granulosa cells. Phase of ovulation :- Ovulation occurs on the 14th day of the cycle. In this phase, there is rupture of Graafian follicle and release of ovum in to the abdominal cavity. Hormonal control It is controlled by LH. LH surge occurs few hours before ovulation and this LH a) increases vascularity of follicles b) increases transudation of fluid into follicle so that it becomes tense c) stimulates secretion of proteolytic enzymes by theca externa. Hence the follicle ruptures and ovum is released. Luteal phase :-Lasts from 15th to 28th day of cycle. After the release of ovum, the rest of Graafian follicle is converted into corpus luteum (yellow body). The granulosa cells and the whole process is called luteinization, these cells start secreting large quantities of progesterone and lesser amounts of oestrogens and inhibin. Theca interna cells secrete androgens which are converted by granulosa calls into oestrogens. The corpus luteum reaches maximum size in 8-9 days, remains for 10-12 days and then undergoes involution by 26th day of cycle to form corpus albicans. However, if fertilization occurs, it remains for 3 to 4 months called corpus luteum of pregnancy. Hormonal control :- All these changes i.e, luteinization and formation of corpus luteum result from action of LH. It also maintains corpus luteum for 10-12 days. The principal function of CL is to secrete progesterone and oestrogens which produce secretary changes in uterine endometrium. Regression of corpus luteum on 26th day is due to withdrawal of LH and FSH secretion resulting from negative feedback effect of Suggestions: facebook.com/asifpatel.ggmc

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176 high progesterone, oestrogen and inhibin levels. If ovum is fertilized, HCG secreted by syncytiotrophoblasts maintains CL for 3 to 4 months.

*Q. DESCRIBE THE ACTIONS OF FEMALE SEX HORMONES: OESTROGENS :- Include beta estradiol, estrone and estriol they are secreted by 1. Granulosa cells of ovary. 2. Placenta 3. Sertoli cells (in males). Actions :- 1. On Uterus :- At puberty and during pregnancy oestrogens cause enlargement of uterus. They produce proliferative changes in endometrium characterized by proliferation of endometrial glands, stromal calls and blood vessels. There is re-epithelialization of endometrium and its thickness increases. Acting on myometrium, they increase thickness and contractility of uterus. Cervical glands secrete thin stringy mucus which shows fern pattern on drying. 2. Vagina :increase in size of vagina and stratification of vaginal epithelium. 3. On ext. genitals :- enlargement of labia majora and minora and fat deposition in mons pubis. 4. On Fallopian tubes :- increase in size, proliferation of glandular tissue, increase in the number and activity of ciliated epithelial cells . 5. On Breasts:- oestrogens cause a) extensive growth of duct system of breasts b) development of stromal tissue c) fat deposition. Hence there is enlargement of breasts. 6. On metabolism:oestrogens increase BMR slightly, they have protein anabolic effect and produce hyperglycemia. 7. Fat deposition :- They promote fat deposition in subcutaneous tissue especially in thighs, buttocks, breasts producing typical feminine figure . 8. Skeleton:- Oestrogens promote bone deposition, bring about growth spurt at the time of puberty but also cause early fusion of epiphyses limiting the height. They also cause development of narrow shoulder girdle and wide pelvis. 9. Skin:- becomes soft, smooth, thick and more vascular. 10. Electrolytes :-Oestrogens cause mild retention of Na= and water. 11. Behavior :- They are responsible for feminine behavior. 12. They increase stickiness of platelets. 13. Stimulate prolactin secretion. 14. Stimulate synthesis of cortisol binding globulin. Mechanism of action:- Oestrogens act at nuclear level stimulating transcription and translation to form new proteins . PROGESTERONE :- Secreted by 1. Corpus luteum. 2. placenta . Actions :- 1. On uterus :- During pregnancy, it causes enlargement of uterus. Acting on endometrium, progesterone causes secretary changes in endometrial glands (uterine milk), deposition of nutrients in stromal cells and proliferation of blood vessels. All these changes provide nutrition to implanted fertilized ovum. It also decreases contractility of myometrium and prevents expulsion of ovum. Acting on cervical glands, it causes secretion of thick mucus (cervical plug) which prevents passage of sperms. 2. On Fallopian Tubes, progesterone causes secretary changes in mucosal lining. 3. On Breasts:- Progesterone causes development of lobules and acini of breasts, mammary gland cells become secretary in nature, there is fluid retention and enlargement of breasts. 4. On Kidneys :- It promotes loss of Na+ and water by causing competitive inhibition of aldosterone . 5. Ovostatic action :- high progesterone levels suppress the positive feedback of oestrogens on LH secretion, thereby preventing LH surge and ovulation. This action forms basis of oral contraceptives. 6. Thermogenic action :- It raises basal body temp by 1/2c during luteal phase. 7. It stimulates respiratory centre and lowers alveolar pCO2. 8. It reduces voltage of EEG waves. Mechanism of action :- It enters cytoplasm of target cells, combines with receptor, the HR combination then enters the nucleus and activates transcription and translation to form new proteins.

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*Q. ENUMERATE THE HORMONES SECRETED BY PLACENTA. DESCRIBE PHYSIOLOGICAL ACTIONS OF HUMAN CHORIONIC GONADOTROPIN :The hormones secreted by placenta are 1. Human chorionic Gonadotropin (HCG) 2. Progesterone. 3. Oestrogens. 4. Human chorionic somatomammotropin (Human placental lactogen) 5. Human chorionic thyrotropin. 6. Relaxin. HCG: It is a glycoprotein hormone made up of 2 subunits, alpha and beta. It is structurally very similar to luteinizing hormone secreted by ant. pituitary. Secretion :- HCG is secreted by syncytial trophoblast cells of placenta soon after the implantation of fertilized ovum. It appears in circulation as early as 7 to 8 days after fertilization. Its conc. starts rising in the initial weeks of pregnancy due to rapid growth of pregnancy. It then falls to very low level after 16th week and remains at that level till the end of pregnancy. The hormone can be detected in urine as early as 8th to 10th day after conception . ACTIONS :- 1. Luteotrophic action :- HCG a) converts corpus luteum of ovarian cycle into corpus luteum of pregnancy b) causes growth of corpus luteum to double its size c) maintains corpus luteum for 3 to 4 months. d) prevents involution of CL. These action are similar to those of Luteinizing hormone. Normally in the absence of fertilization, corpus luteum regresses on 26th day of the cycle due to sudden decrease in the level of pituitary gonadotropins FSH and LH. But if fertilization occurs, the HCG secreted by the syncytiotrophoblasts prevents the involution of corpus luteum and converts it into CL of pregnancy. HCG stimulates corpus luteum to secrete large quantities of progesterone, 17 hydroxy progesterone and oestrogens which produce and maintain secretary change in uterine endometrium. The endometrial glands secrete nutritive fluid called uterine milk and the stromal cells store large amounts of nutrients like lipids and glycogen. These changes are known as decidual changes and they help in nourishment of embryo and continuation of pregnancy. This luteotrophic effect is very essential for continuation of pregnancy because placenta secretes sufficient quantities of progesterone and oestrogens only after 10 to 12 weeks. 2. Luteinizing action :- HCG also has mild luteinizing action, that is it causes conversion of granulosa cells into lutein cells. They increase in size, develop smooth endoreticulum and lipid inclusions and start secreting large quantities of progesterone and oestrogens. 3. Sex differentiation :- In early fetal life (male fetus) HCG stimulates the cells of genital ridge to produce testosterone which helps in formation of male type of external genitals. 4. Descent of testis :- In male fetus, in late fetal life, HCG stimulates the interstitial cells of testis to produce testosterone which then causes descent of testis into the scrotum. 5. It also stimulates secretion of the hormone relaxin from corpus luteum. 6 . HCG stimulates thyroxine secretion during pregnancy . Significance of HCG :- 1 . Early detection of HCG in urine forms basis of pregnancy tests. 2. Useful in diagnosis of hydatidiform mole or teratoma which are the tumors arising from syncytotrophoblasts and in retained placenta. 3. Therapeutically in management of spontaneous early abortions. *Q. DESCRIBE THE PHYSIOLOGICAL CHANGES TAKING PLACE IN MOTHER DURING PREGNANCY: Various maternal changes during pregnancy include :- 1. Changes in uterus and birth canal – There is enlargement of uterus due to hypertrophy and hyperplasia brought about by actions of oestrogens and progesterone. Its weight increases from 50 gms to 1100 gms. Endometrium shows secretary (decidual) changes due to action of the above hormones. There is enlargement of birth canal and relaxation of pelvic ligaments due to relaxin. 2. Changes in ovary: There is enlargement of ovaries, formation of a single large corpus luteum of pregnancy and stoppage of ovarian cycles and ovulation due to low levels of pituitary gonadotropins. 3 Changes in breasts : Proliferation of ducts (due to oestrogens) and that of alveoli and lobules. (progesterone) secretary apparatus becomes ready, but there is no milk secretion during pregnancy(except few ml of colostrum in late pregnancy). There is pigmentation of nipple and areola. Also there is water Suggestions: facebook.com/asifpatel.ggmc

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178 retention and enlargement of breasts. 4.CVS :- There is increase in cardiac output by 30% to provide additional 600- 650ml blood to placenta. Heart rate, venous return increases. Diastolic pressure may fall. 5. Blood Volume :- increases by 30% especially in latter half of pregnancy due to retention of Na+ and H2O brought about by aldosterone and oestrogens. 6. Blood: erythropoiesis is stimulated but the increase in fluid volume is more. Hence there is anaemia (of pregnancy) ESR is increased due to anaemia. 7.Respiration :- There is about 50% increase in resting minute volume due to increased metabolism, greater O2 requirements and greater CO2 production. Progesterone also increases sensitivity of respiratory center to CO2. Alveolar pCO2 falls. Respiratory rate is increased due to enlarged uterus pressing on the diaphragm and limiting its movements. 8. Metabolic changes :BMR increases by 15 to 20 % due to excess secretion of thyroxine and sex hormones. Glucose tolerance is reduced. Deficiency of iron, vitamins D and K may develop. 9. Weight gain :- Body weight increases due to a) weight of fetus, placenta, amniotic fluid . b) growth of uterus c) fluid retention d) fat deposition. 10. Endocrinal changes :- A) Placenta :- secretes various hormones like HCG, oestrogens, progesterone, chorionic somatomammotropin etc. which maintain pregnancy . B) Ant pituitary :- secretion of TSH, ACTH and prolactin is increased while that of FSH and LH is reduced due to negative feedback effect of high oestrogen and progesterone levels . C) Thyroid gland increases in size by 50% and there is increase in thyroxine secretion due to the action of placental HCG and HCT D) Parathormone secretion is increased which helps in mobilization of calcium from mother to fetus. E) Adrenals :- There is increased secretion of aldosterone which causes fluid retention and that of cortisol which makes amino acids available for synthesis of fetal protein. 11. Excretory system :- There is increase in glomerular blood flow and GFR. Reabsorption of Na+, Cl- and H2O is also increased. Urine output increases slightly . *Q. DESCRIBE THE HORMONAL CONTROL OF LACTATION : The process of lactation involves formation of milk and its expulsion from the breasts. Hormones controlling lactation are :1 . Role of oestrogens :-Oestrogens cause growth and proliferation of ductal system ( ductules, ducts and lactiferous tubules ) of the breasts . They also cause development of stroma of breast tissue and deposition of fat in the breasts . These actions are seen at the time of puberty and also during pregnancy. 2. Role of progesterone :- After the development of ductal system, progesterone along with oestrogens causes growth and proliferation of lobules, budding of alveoli and development of secretary changes in alveolar cells of mammary glands. It also causes fluid retention and enlargement of breasts. 3. Role of prolactin :- Prolactin secreted by ant. pituitary acts on breasts primed by oestrogens and progesterone and is responsible for initiation of milk secretion (lactogenic action) and for continuation of milk secretion (galactopoiesis). During pregnancy, high blood levels of progesterone and oestrogens have a suppressing effect on lactogenic action of prolactin, hence there is no milk secretion during pregnancy (only few ml of fluid called colostrum is secreted a few days before parturition.) After birth of the baby, blood levels of these hormones fall and prolactin exerts full lactogenic effects. Mechanism of action :- prolactin activates mRNA in alveolar cells leading to formation of new proteins and enzymes causing synthesis of milk components like lactalbumin, casein, lactoglobulin, lactose and fats. Regulation of prolactin :principal stimulus for prolactin secretion is suckling during which impulses are transmitted to hypothalamus which inhibit Prolactin Inhibiting Factor (or stimulate prolactin releasing factor) and prolactin is released from ant. pituitary .Each prolactin spurt lasts for about 1 hour and promotes milk secretion for subsequent feeds. 4 . Human chorionic somatomammotropin :- or human placental lactogen secreted by placenta helps in development of breasts and has mild lactogenic effect . Suggestions: facebook.com/asifpatel.ggmc

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5 . Oxytocin:- brings about milk ejection into the ducts. This action is important because even though milk is secreted, it does not flow spontaneously into the ducts. Secretion of oxytocin :- during suckling, tactile receptors in nipple and areola are stimulated and afferent impulses are carried to paraventricular nuclei of hypothalamus causing release of oxytocin form post pituitary. It then reaches the breast through circulation and causes contraction of myoepithelial cells surrounding the alveoli so that milk is squeezed into the ducts and made available to the baby. This is called milk ejection reflex or milk letdown which is a neuroendocrine reflex. Psychogenic factors or generalized symp. activation can inhibit oxytocin release and milk ejection. 6. Other hormones like growth hormone, insulin, cortisol and parathyroid hormone also help in the process of lactation by promoting growth of breasts and by providing amino acids, fatty acids glucose and calcium which are required for milk synthesis. *Q. DECRIBE THE MECHANISM THAT MAINTAIN BODY TEMPERATURE WHEN EXROSED TO COLD ENVIRONMENT :- Man is homoeothermic animal and the temperature of human body is maintained at 370 C, when the body is exposed to cold environment, the cold receptors in skin are stimulated and they send afferent impulses to hypothalamus and also to higher centers. The post. hypothalamus contains the center which is concerned with response to cold (antidrop center). When stimulated it brings about various autonomic, somatic and endocrinal responses which 1. Decrease heat loss from body and 2. Increase heat production in body. In addition, higher cortical centers also initiate various behavioral mechanisms serving the same function. Mechanism to decrease heat loss from body: 1. Cutaneous vasoconstriction :- post. hypothalamus transmits impulses through the sympathetic fibers to cutaneous blood vessels causing their constriction. Decrease in cutaneous blood flow prevents transfer of heat from body core to surface (shell). Moreover heat loss from skin by various ways like conduction (heat loss from body to cooler objects which are in contact with body) convection (heat loss in warming the layer of cold air around the body) and radiation (heat loss to surrounding cooler objects by electromagnetic radiations) are also reduced. 2. Horripilation (piloerection). Sympathetic discharge to errector pili causes hair to stand on and, there by trapping a thicker layer of air around the body which acts as insulator and prevents heat loss. Useful mechanism in furred animals. 3. There is inhibition of sweating so that evaporative heat loss is reduced. However, insensible perspiration continues. Mechanism to increase heat production:Shivering : is a somatic response and consists of alternate contractions and relaxations of skeletal muscle without affective movement. Heat is generated in this process when the environmental temperature falls below a critical value (230C), the shivering centre situated in dorsomedial part of post. hypothalamus is activated and sends impulses to spinal Motoneurons increasing their tone. When muscle tone exceeds certain level, shivering occurs due to oscillation of muscle spindle stretch reflex mechanism causing large heat production. Chemical thermogenesis :- A) sympathetic activation and release of epinephrine and norepinephrine in blood increases heat production by causing uncoupling of oxidation and phosphorylation, so that energy released on oxidation appears as heat. The heat generated by this mechanism depends upon the quantity of Brown fat which contains special mitochondria and is an important mechanism for heat production in infants. B) Role of thyroid hormones:- prolonged exposure to cold causes release of TRH from hypothalamus, and thus of TSH from ant. pituitary which then acts on thyroid gland and increases T3 and T4 secretion. The hormones then increase cellular metabolism and heat production. C) Behavioral changes: to counteract effects of cold are 1. Increased muscular activity like rubbing of hands, stamping of feet. 2. Curled up position in bed to decrease exposed surface area. 3. Use of woolen clothes. 4. Increased hunger and food intake to increase metabolic heat. 5. Sitting close to fire etc. Suggestions: facebook.com/asifpatel.ggmc

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180 *Q. DESCRIBE THE MECHANISM THAT MAINTAINS BODY TEMPERATURE WHEN EXPOSED TO HOT ENVIRONMENT :Man is a homeothermic animal and the human body temperature is maintained at 370C inspite of wide fluctuations in environmental temperature. When the body is exposed to high temperature, the peripheral warmth receptors (thermoreceptors) in skin are stimulated and send afferent impulses to hypothalamus and to higher centers. In addition there are central thermoreceptors (heat sensitive neurons) situated in ant hypothalamus which are stimulated by rise in temperature of blood. The center for responses to high temperature is situated in preoptic and ant hypothalamic regions (anti rise center). When stimulated, this center initiates the mechanisms for heat loss from the body and suppresses heat production. In addition, higher centers initiate behavioral changes serving the same function. Mechanism for Heat loss : Cutaneous vasodilation :- it results from inhibition of symp. Centre in post. hypothalamus causing increase in blood flow to skin and subcutaneous venous plexus. This facilitates transfer of heat from core of the body in various ways like conduction (heat loss to cooler objects which are in contact with body), convection (heat loss in warming the layer of cooler air around the body), and radiation (heat loss to surrounding cooler objects by electromagnetic waves). Cutaneous vasodilatation also facilitates sweating. Sweating:- stimulation of pre-optic area leads to profuse sweating by increasing the discharge through symp. cholinergic fibers supplying sweat glands. The process of sweating starts when the body temperature exceeds the set point of hypothalamic thermostat (370C). Sweating increases evaporative heat loss. When 1 gm of water evaporates from skin 0.58 kcal of heat loss when the body is exposed to high environmental temperature, because the other mechanisms like conduction, convection and radiation fail to cause heat loss. Dry air and circulation of air facilitates while humidity of air opposes evaporation. Some heat is also lost by insensible perspiration which is a continuous process of diffusion of water molecules thought skin pores. Panting :- it is a mechanism for heat loss in those animals who do not have sweat glands. Rise in body temperature causes rapid shallow respirations, so that more water evaporated from respiratory passages into expired air. Salivation :- In some animals, rise in body temperature stimulates salivary secretion and heat is lost in the process of evaporation of saliva. There is strong inhibition of mechanism causing heat production such as shivering and chemical thermogenesis. Behavioral responses: a) reduced muscular activity to decrease heat production b) use of light and minimum clothes to promote heat loss c) loss of appetite and decreased food intake so that less heat is generated d) air circulation by fans e) cold shower, cold drinks etc. Applied physiology:- 1. Lesion in preoptic area causes hyperthermia. 2. During remission of a fever, hypothalamic thermostat is suddenly set at low value leading to profuse sweating. *Q. ENUMERATE VAROUS METHODS OF CONTRACEPTON. DESCRIBE ANY TWO METHODS OF CONTRACEPTION IN FEMALES : Methods of contraception :- A) in males :- a) temporary methods:- 1. Use of condom 2. Azoospermic agents like gossypol 2. coitus interruptus (withdrawal) b) permanent : bilateral vasectomy, In females. a) Temporary methods: 1. Oral contraceptives 2. Intrauterine contraceptive device 3. Rhythm method (safe period) 4. Barriers like vaginal diaphragm, cervical gap. 5. Use of spermicidal agents in various forms like foams, pastes, jellies, peccaries etc. b) permanent :- Bilateral tubectomy. Suggestions: facebook.com/asifpatel.ggmc

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ORAL CONTRACEPTIVES :Are the pills or tablets taken orally by the women to prevent conception. Contents:these tablets contain small amounts of synthetic oestrogens like ethenyl estradiol or mestranol and synthetic progesterone like norethindrone or norgestrol. Synthetic hormones are not easily destroyed in liver, hence remain in blood for long periods. Mechanism of actions :1. Ovostatic action :- These hormones especially progesterone, prevents occurrence of preovulatory LH surge by suppressing the positive feedback effect of oestrogens on LH secretion. Therefore ovulation does not occur, hence no risk of fertilization. 2. Cervical mucus :- under the influence of progesterone, cervical mucus becomes thick and forms an impenetrable plug in the cervix which opposes the passage of sperms. 3. They also prevent implantation of fertilized ovum. Administration:- oral contraceptives are available in packets containing 28 tablets of which 7 tablets (red colored) are iron tablets. They are taken from 5th to 25th day of cycle, followed by iron tablets for 7 days. Types of pills :- 1. Combined pills: containing both oestrogen and progesterone. 2. Sequential pills: containing oestrogens only for first 16 days and then oestro-progesterone combination for subsequent 5 days. 3. Mini pills :- contain only progesterone. Side effects:- Nausea, vomiting break through bleeding, weight gain, hypertension, breast tenderness. Contraindications:- liver diseases, thromboembolic conditions, cancer of breasts and uterus. Advantages:- oral contraceptives provide the best temporary method for contraception, especially for spacing the children. They can also be used as post coital contraceptive.

*Q. INTRAUTERINE CONTRACETIVE DEVICE (IUCD): It is a device implanted in the cavity of uterus to prevent pregnancy. Types :- there are various types of IUCDs like copper T(200), Lippes loop, Sooriawala loop etc. of which copper T is commonly used. It is a T shaped plastic device 3mm long and 32 mm wide. At the lower end of vertical limb, 2 Nylon threads are attached which confirm the presence of copper in uterus and which can be used to pull it out, if necessary. A copper wire is wound around the vertical limb of the T which has a surface area of 208 mm2. Mechanism of contraceptive action: 1. IUCD elicits foreign body inflammatory reaction in endometrium, So that uterine environment becomes hostile and the implantation of fertilized ovum does not occur. 2. Cu++ ions inhibit the enzyme carbonic anhydrase in endometrium. 3. Cu++ also interferes with actions of estrogens on uterus. 4. IUCD also speed the passage of fertilized ovum through the uterus preventing its implantation. Insertion: - It is implanted into uterine cavity by using an inserter and a plunger through the vaginal route. Insertion is done in post menstrual phase or few weeks after delivery. Side effects: - Pain in abdomen, bleeding from uterus, menstrual disturbance, expulsion, pelvic infections, perforation of uterus ectopic pregnancy. Contraindications: - Pelvic infections, fibroids, endometriosis, cancer of cervix or uterus. Advantages: - Especially useful for spacing the children. However it should not be used continuously for more than 3 years.

SHORT NOTES: *Q. SAFE PERIOD (RHYTHM METHOD OF CONTRACETION):Safe period is the period in menstrual cycle during which conception will not occur and hence sexual intercourse is ‘safe’. Principle: - It is one of the temporary methods of contraception and is asked on the knowledge of day of ovulation and survival of sperms and ovum in the female genital tract. Normally the ovulation occurs on the 14th day of a 28 day regular menstrual cycle. This ovum can survive for a period of up to 48 hours. Similarly, the sperms, after their deposition in female Suggestions: facebook.com/asifpatel.ggmc

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182 genital tract can live up to 34 to 48 hrs. Therefore in a regular menstrual cycle, the fertile period extends from 12th to 16th day of the cycle and intercourse should be avoided on these days to prevent conception. Other days of the cycle are safe period days. Disadvantages:- The biggest drawback of this method is uncertainty of day of ovulation. The ovulation occurs 14 days before the onset of next menstrual cycle which however, cannot be predicted due to irregularity of duration of cycles. Therefore, safe period is generally calculated by subtracting 18 from shortest duration of cycle and by subtracting 11 from longest cycle. Hence in a woman with menstrual cycle duration varying from 25 to 32 days, safe period extends up to (25-18) 7th day of cycle and 21st day (32-11) onwards. In general, avoidance of intercourse from 11th to 18th day of the cycle will prevent conception. Failure rate is very high in this method and it should be used in combination with other methods like use of condoms, spermicidal jelly’s etc.

*Q. PUBERTY:Puberty is defined as onset of reproductive life in a male or female (onset of sexual life). It occurs at around 14 to 15 years in boys and 13 years in girls. Cause of puberty: - It results from some maturation process taking place in brain at that age so that the hypothalamus starts secreting Gonadotropin releasing hormone which acts on ant. pituitary to release FSH and LH which then act on gonads (testis and ovaries)to produce sex hormones. Changes occurring in the body at the time puberty:- 1. Sex organs and external genitals that is ovary, uterus, fallopian tubes, vagina, labia etc. in female and testis, vas deferens, epididymis, seminal vesicles, prostate, penis, scrotum etc. in males grow rapidly. Spermatogenesis starts. 2. In girls, there is onset of ovarian and menstrual cycle (menarche). 3. Secondary sexual characters develop like growth of beard, moustaches, public, axillary hair, hair on chest, deep hoarse. Low pitched voice in males and growth of breasts, feminine fat distribution, axillary and public hair, high pitched feminine voice etc. in females. 4. Emotional behavior rapid increase in height (growth spurt) due to action of sex hormones on long bones. Skeleton shows typical like wide shoulders and narrow pelvis in males, and narrow shoulders, carrying angle and wide pelvis in females. 6. Endocrinal changes like secretion of FSH, LH and testosterone (in males) and estrogens and progesterone (in female). There is increase in secretion of adrenal androgens. Applied Physiology :Damage to hypothalamus can cause delayed puberty or tumors like teratoma in childhood can cause precocious puberty.

*Q. MENOPAUSE: Menopause is the physiological condition characterized by stoppage of ovarian and menstrual cycles in woman. It marks the end of the reproductive life and occurs between 45 to 50 years. Cause:- It is a gradual process and is due to non-responsiveness of ovaries to pituitary gonadotropins, FSH and LH. Hence formation of Graffian follicle and ovulation does not occur. Secretion of estrogen (by granulosa cells) and progesterone falls drastically, therefore menstrual cycles also stops. Changes at Menopause: 1. Atrophy of ovaries, uterus and fallopian tubes. 2. Vagina becomes atrophic and thin walled 3. Atrophy of the breasts. 4. There is increase in blood levels of FSH and LH due to loss of negative feedback effect of sex hormones. 5. Menstrual cycles become irregular, an ovulatory and then stop.6. Hot flushes which are characterized by sensation of warmth, sweating and flushing of face, either due to lack of estrogens or rise of LH. 7. Psychological disturbances like anxiety, depression, irritability, dyspnea, fatigue etc. are also seen. 8. Osteoporotic changes and fractures may occur due to mobilization of bone matrix in absence of estrogens.9. Pain in joints and arthritis. All the above changes are due to deficiency of estrogens though some oestrone is Suggestions: facebook.com/asifpatel.ggmc

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secreted by adrenal cortex. Treatment :- 1. Proper explanation to the subject that it is a natural phenomenon. 2. Administration of small daily dose of estrogen, if necessary.

*Q. IMMUNOLOGICAL TEST TO DETECT PREGENCY:Tests carried out to detect or to confirm the pregnancy are called pregnancy test. They are of 3 types 1. Immunological 2.Biological(carried out in lab animals) and 3. Clinical . Immunological test (Gravindex test) : Principle : It is based on detection of human chorionic gonadotropin hormone (HCG) in the urine (of woman suspected of pregnancy) by immunological method. This hormone is secreted by syncytiotrophoblast cells of implanted ovum and appears in urine as 8 to 9 days after conception. Procedure :- It is an agglutination test carried out on a black colored glass slide with 2 depressions called Gravindex slide. In one depression, 2 drops of test urine and in the other 2 drops of control (non pregnant, urine are taken 2 drops of anti HCG serum are added to each of these depressions and mixed thoroughly. Then 2 drops of latex particles coated with HCG antigen are added to each depression and mixed again. Observation :- If woman is pregnant, her urine will contain HCG which will react with and neutralize anti HCG. Hence no Anti HCG will be left to agglutinate subsequently added latex particles. Therefore absence of agglutination of latex particles indicates positive pregnancy test. On the other hand, non-pregnant control urine will show agglutination because it does not contain HCG to neutralize anti HCG which will then cause agglutination of latex particles coated with HCG. Advantages of the test:- 1. Highly reliable. 2. Quick results within 2 to 3 minute. 3. Easy to perform. 4. Lab animals not required 5. No harm to patient. 6. Helpful in early diagnosis of pregnancy. 7. Useful in diagnosis os retained placenta. Drawbacks :- The test is false positive in conditions like chorionepithelioma or teratoma, which are tumors arising from syncytiotrophoblasts producing HCG. *Q. FUNCTIONS OF PLACENTA:Placenta is cake(?) shaped organs that serves as various functions. 1. Respiratory functions: a) O2 diffuses through the placental membrane from maternal blood (pO2 50 mmHg) to fetal blood (pO2 30 mmHg). O2 Uptake by fetal blood is facilitated by i) fetal Hb having greater affinity for O2 ii)more amount Hb iii) Bohr effect b) CO2 diffuses from fetal blood to maternal blood for elimination. 2. Nutritive function :- various nutrients which are required for the growth of fetus are transported through placenta by mechanisms like simple diffusion, facilitated diffusion or active transport. They include glucose, fructose, amino acids, fatty acids, ascorbic acid, Ca+ and electrolytes like Na+, K+, Cl- etc. 3. Excretory function :- placenta excretes waste products from fetus into maternal blood like urea, uric acid and creatinine by the process of diffusion. It also controls diffusion of fluids and fluid volume. 4. Endocrine functions :- placenta secretes various hormones like a) HCG:- which maintains corpus luteum of pregnancy b) Oestrogens and progesterone :- which maintain decidual changes in endometrium and prepare the breasts for lactation. Synthesis of these steroid hormones occurs partly (some stages) in placenta and partly in fetal tissues. Thus fetus and placenta work as single unit (fetoplacental unit) in sterol digenesis c) HC somatomammotropin :- which promotes growth of fetus and mother’s breasts d) Thyrotropin – which stimulates maternal thyroid during pregnancy e) Relaxin :- Which relexes pelvic ligaments of mother. 5) Storage function:- Placenta stores glycogen, fats, etc. 6) Protective function: Transports immunoglobulins to fetus and gives passive immunity. *Q. Brown fat:Is a special type of fat present mainly in fats and in some animals living in cold climates like polar bear. Adult humans contain very small quantity. Distribution :- This fat is found in the interscapular region, around the scapulae in the nape of neck and along the great vessels in thorax and abdomen. Peculiarities of brown fat cells :- 1. They contain many fat droplets instead of one. 2. They contain Suggestions: facebook.com/asifpatel.ggmc

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large number of special type of mitochondria in which there is uncoupling of oxidation and phosphorylation. The energy that is released on oxidation of substances is not utilized for formation of ATP, instead it is released as heat. 3. The cells are richly supplied by sympathetic fibers. Functions : 1. Chemical thermogenesis : When the body is exposed to cold, there is activation of sympathetic system and release of noradrenaline from nerve ending and adrenaline from adrenal. These hormones act on beta-adrenergic receptors of brown fat cells and stimulate lipolysis with formation of fatty acids. These fatty acid are oxidized in mitochondria to produce large amounts of heat. This is called non-shivering thermogenesis and can increase metabolism in infants by 100%. This heat producing mechanism is especially important in new born because shivering is not developed at this stage In adults brown fat can increase metabolism only by 10 to 15%. 2. Brown fat heat production is one of the acclimatization mechanism on prolonged exposure to cold. Applied aspect:- Defective uncoupling in brown fat cells may be one of the factors in genesis of obesity. *Q. FEVER (PYREXIA) :Fever or pyrexia is a condition in which body temperature rises above the normal range. Conditions which produce fever are 1. Bacterial infections e.g. pneumonia, typhoid, urinary tract infections etc. 2. Tumors or other lesions of brain (hypothalamus) 3. Exposure to very high environmental temp (heat stroke) Mechanism of fever :- The toxins released by the bacteria contain certain lipopolysaccharides called exogenous pyrogenes. These act on macrophages, monocytes and Kupffer’s cells causing release of interleukin 1 or endogenous pyrogen. Interleukin 1 then causes formation of prostaglandins which act on the neurons of preoptic area of hypothalamus and reset the hypothalamic thermostats at higher value i.e. 390 or 400C. The hypothalamus then interprets that the existing body temp is less than reset value and therefore initiates mechanism for heat production like shivering (rigors) and for heat conservation like cutaneous vasoconstriction (chills) Thus the body attains a higher temp that is fever. When treated hypothalamus thermostat is reset at a lower value, therefore hypothalamus initiates mechanism for heat loss, via cutaneous vasodilatation and profuse sweating (crisis) Advantages: - 1. Rise in body temp helps to kill or inactivate some of the bacteria 2. It also accelerates the process of antibody formation. Disadvantages:- Very high temp. can cause brain damage. Applied aspect :- Antipyretics like aspirin suppress prostaglandin synthesis and prevent pyrogenic effect of interleukin.

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May/ June 2007 SAQ 1. Give causes and physiological basis of treatment of peptic ulcer. 2. What is parturition? Explain role of oxytocin in parturition. 3. Define hypoxia. Enumerate the types of hypoxia. Describe any one of them. 4. Enumerate various gastrointestinal hormones. Write a note on cholecystokinin. 5. Draw a labeled graph of oxygen-hemoglobin dissociation curve. Explain role of 2-3 BPG. 6. What is the hypothermia? Explain body mechanisms in response to cold. 7. What is the difference between isotonic and isometric exercise? Explain the effect of isotonic exercise on blood pressure. LAQ 1. Enumerate hormones of pituitary gland. Describe mechanism of action and function of growth hormone. Add a note on dwarfism. 2. Define heart rate. What are the factors affecting and regulating heart rate? Explain. 3. What is lung compliance? Enumerate and explain the factors affecting lung compliance. Add a note on hyaline membrane disease. May/June 2008 SAQ 1. Haldane effect 2. Role of hypothalamus in temperature regulation. 3. Venous return. 4. Cushing's syndrome. 5. Factors affecting stroke volume. 6. Hormones and uterine changes during menstrual cycle with help of a diagram. 7. Absorption of fat. LAQ 1. Circulatory Shock. Stages of shock. Physiological basis of its management. 2. Chemical control of respiration. 3. Enumerate gastric secretions. Their mechanism of action and regulation of secretion.

Nov/Dec 2008 SAQ 1. Draw a neat labeled diagram of ECG complex. Explain bipolar limb leads. 2. Describe the circulatory changes at birth. 3. Define and classify Hypoxia. Describe any one of them. 4. Draw a neat and labeled Oxygen Hemoglobin Dissociation Curve. Enumerate factors shifting the curve to right. What is P ? 5. Differentiate between Diabetes Mellitus and Diabetes Insipidus. 6. Describe the bodily responses on exposure to cold. Mention the use of induced hypothermia. 7. What are the movements of large intestine? Explain 'Defecation reflex'. LAQ 1. Events in cardiac cycle. Add a note on heart sounds. 2. Describe the mechanism and regulation of hydrochloric acid secretion. Explain the basis of drugs used in the treatment of peptic ulcer. 3. Describe the cyclical changes in the uterus during reproductive life. Write about its hormonal regulation. 50

May/June 2009 1. Enumerate the properties of cardiac muscle. Explain why cardiac muscle cannot be tetanised. 2. Name the muscles of respiration. Describe the mechanism of breathing. 3. Describe the functions of bile salts in fat digestion and absorption. 4. What is Cushing's syndrome? Describe its clinical features. 5. Describe the phases of menstrual cycle. 6. Define Hypoxia. What are the types of hypoxia? Describe hypoxic hypoxia. 7. Describe the heat loss mechanisms of the body. LAQ 1. Define stroke volume, cardiac output, cardiac index and stroke volume index. Describe the factors affecting cardiac output. 2. Enumerate the hormones secreted by ant. Pituitary. Describe the physiological actions of growth hormone. 3. Give the composition of gastric secretion. Describe the functions and mechanism of secretion of HCl. Nov/Dec 2009

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186 SAQ 1. Describe the various changes occurring during acclimatization to high altitude. Add a note on acute mountain sickness. 2. What is gastric emptying? Explain the various factors regulating it. 3. Give the composition of bile and the functions of bile salts. 4. Enumerate the functions of surfactant. Add a note on its clinical significance. 5. Describe oxygen debt. 6. What is ovulation? Describe the methods of contraception used in women. 7. What is Fick's principle? Describe the method of cardiac output estimation using this principle. LAQ 1. Describe the method of oxygen transport in the body. 2. Classify the mechanism of regulation of blood pressure. Explain briefly the short term regulation of blood pressure. 3. Describe the synthesis, regulation and functions of thyroid hormone. Add a note on hypothyroidism.

May/June 2010 SAQ 1.Explain mechanisms of ovulation and describe rhythm method of contraception. 2. What is heart block? Enlist types of heart block. Explain atrioventricular nodal block. 3. What is deglutition? Explain the pharyngeal stage of deglutition. 4. State the various methods by which heat loss occurs from the skin to the surroundings. Add a note on mechanism of sweating. 5. Define heart rate. Explain increase in heart rate during moderate muscular exercise. 6. Explain the effect of acute and chronic exposure to low partial pressure of oxygen in inspired air on pulmonary ventilation. 7. What is Tetany? Name and explain signs of Tetany. Write its treatment. LAQ 1. Define mean arterial blood pressure. Enumerate various mechanisms regulating blood pressure. Describe baroreceptor reflex. 2. State various layers of respiratory membrane. Describe the various factors that affect rate of gas diffusion through the respiratory membrane. Give principle of carbon monoxide method for calculating oxygen diffusing capacity through it. 3. What is composition of gastric juice? Explain the mechanism of hydrochloric acid secretion by the stomach. State the factors that stimulate hydrochloric acid secretion. Nov/Dec 2010 1. Explain Renin Angiotensin mechanism. 2. Describe regulation of gastric motility. 3. Describe maternal changes in last trimester of pregnancy. 4. Explain physiological basis of oedema. 5. Define functional residual capacity. What is its physiological significance. 6. Explain the mechanism of heat loss from the body. 7. Describe the factors affecting caloric requirement in a thirty year old female. LAQ 1. Define ECG. Explain ECG as seen in Lead II with a neat labeled diagram. Add a note on heart block. 2. Describe the hormonal regulation of physical and mental growth. Add a note on differences between a pituitary and a Thyroid dwarf. 3. Describe the mechanism of pulmonary ventilation. Add a note on positive pressure breathing. May/June 2011 1. Explain the movements of large intestine. Add a note on defecation reflex. 2. Explain the work of breathing. Add a note on its applied importance. 3. Name the different thermoreceptors. Explain body mechanisms in response to hot environment. 4. Enumerate various GIT hormones. Write a note on gastrin. 5. Describe tissue fluid formation. 6. Write answer on: Diabetes insipidus and Cushing's syndrome. 7. Temporary methods of contraception LAQ 1. Describe regulation of calcium level in the body. Add a note on osteoporosis. 2. Define and classify circulatory shock. Describe the progressive stage of shock. 3. Describe nervous regulation of respiration. Add a note on Ondine's curse.

Nov/Dec 2011 1. Enumerate the factors which increase insulin secretion. What is the effect of insulin to promote growth? 2. Describe the transport of carbon dioxide in blood. What is Haldane effect?

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3. Describe the response of the body to extreme cold. 4. Describe stage II of deglutition reflex. What is the importance if deglutition reflex? 5. Describe the physiological changes occurring during pregnancy. 5. Describe the peculiarities of coronary circulation. What is angina pectoris? 6. Describe the effects of exercise on respiration. What is VO max? LAQ 1. Enumerate different gastric glands, their secretion and function. Describe the physiological basis of treatment of peptic ulcer. 2. Enumerate the hormones secreted by adrenal cortex. Describe factors regulating secretion of aldosterone. 3. Describe the events in cardiac cycle occurring in the ventricles. 2

Nov/Dec 2012 SAQs 1. Explain role of juxtaglomerular apparatus in regulation of blood pressure. 2. Define and classify hypoxia. 3. What are the different ways of heat loss from the body? Add a note on peptic ulcer. 4. Mechanism of secretion of HCl in stomach. Add a note on peptic ulcer. 5. Describe spermatogenesis and factors affecting it. 6. Describe physiological actions of growth hormone on metabolism in the body. 7. What is surfactant? State its functions. Add a note on Respiratory distress syndrome. LAQ 1. What is the importance of calcium in the body? Explain the regulation of calcium level. Add a note on Tetany. 2. Define and classify shock. Describe the compensatory stage of circulatory shock and physiological basis of its treatment/management. 3. Explain nervous regulation of respiration. Write a note on Ondine's curse. May/June 2013 SAQ 1. Describe ECG in lead II. 2. Oxygen debt. 3. Describe movements of small intestine. What is peristaltic rush? 4. Describe the various changes that occur at high altitude(Acclimatization). 5. Describe metabolic actions of growth hormone. 6. Define and classify circulatory shock. Enumerate physiological principles of its management. 7. Describe mechanism of secretion of HCl in stomach. Add a note on peptic ulcer. LAQ 1. Describe various phases of menstrual cycle. Discuss its hormonal control. 2. Define blood pressure. Discuss the long term regulation of blood pressure. 3. Describe respiratory membrane and factors affecting gaseous exchange across respiratory membrane. PHYSIOLOGY II

May/June 2007 SAQ 1. Draw a neat labeled diagram of nerve action potential. Give its ionic basis. 2. Explain functions of middle ear. What are the tests for hearing and deafness? 3. Explain functional basis of connections of cerebellum. Give their clinical abnormalities. 4. What is juxtaglomerular apparatus? Explain tubuloglomerular feedback mechanism. 5. Enlist various mechanisms for the transport of substances across membrane. Describe one of them. 6. Describe stages of erythropoiesis. Name the factors regulating it. 7. Describe synaptic transmission in flow chart. What are the various types of the synaptic inhibitions? LAQ 1. Enumerate the descending tracts of the spinal cord. Describe origin, course, termination and functions of corticospinal tract with its applied significance. 2. Discuss photochemistry of vision in detail. 3. What is sarcomere? Describe the molecular basis of skeletal muscle contraction and relaxation. May/June 2008

Q. Compare and contrast between fast and slow pain. Q. Draw a well labeled diagram of Neuron. Dfine Nerve impulse. Q. Define GFR. What is tubuloglomerular feedback and glomerulo-tubiular balance. Q. Trace the pathway for taste sensation. Enumerate basic modalities of taste and type of papillae.

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188 Q. What is myasthenia gravis? How is it treated ? Q. Define memory. Enumerate types of memory.What is Alzhimer's disease? LAQ Q. Define resting membrane potential. Discuss ionic basis for development of resting membare potential and action potential. Q. Describe connections and functions of cerebellum with applied importance. Q. Define Milieu interior. Explain the role of kidney in maintaining the osmolarity of body fluid.

Nov/Dec. 2008 Q. Define resting membrane potential. Explain ionic basis of RMP in a nerve fibre. Q. Describe the molecular basis of muscle contraction in skeletal muscle. Q. Define and classify immunity. Explain role of different types of T cells. Q. Describe innervation of urinary bladder. Explain micturation reflex. Q. Draw and label important areas of frontal lobe. Enlist functions of prefrontal lobe. Enlist functions of prefrontal lobe. Q. What are different types of sensory receptors ? Enlist properties of receptors. Explain adaptation and intensity discrimination. Q. Which are physiological and pathological errors of refraction. Explain features and correction in myopia and astigmatism. LAQ Q. Describe the connections and functions of basal ganglia. Q. What is glomerular filtration rate? Explain various factors affecting GFR. How is it measured? Q. Describe photochemistry of vision. What is dark adaptation? May/ June 2009 Q. Define bleeding time and clotting time. Describe intrinsic pathway of coagulati0n. Q. Describe counter current mechanism. Q. Compare and contrast action potential and excitatory postsynaptic potential in neurons. Q. Olfactory pathway Q. Parkinsonism Q. Properties of receptors Q. Neuromuscular junction LAQ Q. Classify white blood corpuscles. Describe morphology and functions of WBCs. Q. Describe origin, course, termination and functions of pyramidal tracts. Q. Outline main functions of different lobes of neocortex.

Nov/Dec 2009 SAQ Q. What is saltatory conduction? What are the factors affecting conduction velocity in nerve? Q. Define lower motor neuron. What are the clinical features of lower motor neuron paralysis? Q. Draw neat and labeled diagram of Corti. Enumerate the causes of nerve deafness. Q. What is accommodation reflex? Write a note on Presbyopia. Q. State Landsteiner's law. What is the importance of Rh blood group? Q. Explain the functions of proximal convoluted tubule of nephron. Q. Name ascending tracts. Draw a labeled diagram of pain pathway. LAQ Q. Name different nuclei of hypothalamus. Explain various functions of hypothalamus. Q. What is clotting? Give flow chart of mechanism of blood coagulation. Name two anticoagulants. Q. Draw and label the diagram of Neuromuscular junction. What are the sequence of events in neuromuscular transmission of impulse? Write a note on myasthenia Gravis. May/June 2010 Q. What is erythroblastosis fetalis? Write its clinical features and physiological basis of treatment. Q. Draw a well labeled diagram of neuromuscular junction. What is end plate potential? How is it generated? Q. Types of pain. Neospinothalamic pathway. Q. Define GFR. What are factors affecting GFR? Q. Place principle. Explain role of basilar membrane in perception of sound frequencies. Q. Define homeostasis. Give characteristics of negative feedback mechanism with examples. Q. Functions of basal ganglia. What are clinical features of parkinsonism? LAQ Q. Define immunity. Describe humoral immunity. What is the principle of vaccination? Q. Enumerate functions of hypothalamus. Describe any two of them in detail.

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Q. Define accommodation. Describe the mechanism and neural pathway for accommodation. Add a note on Presbyopia.

Nov/Dec. 2010 Q. What is Glomerular filtration rate? Enumerate factors affecting GFR. Q. What is normal count of platelet? write functions of platelets. Q. Define oxygen debt. Explain the mechanism involved in dark adaptation. Q. A patient has low RBC count and microscopic examination of his blood revealed high percentage of circulating reticulocyte. Upon subsequent examination the patient is diagnosed with bleeding ulcer. Q. After surgical treatment the blood picture of patient became normal. Explain the reason of low RBC count and high percentage of reticulocyte. Q. What is aphasia? Explain different types of aphasias. Q. Write about the features of REM sleep. LAQ Q. Descibe physiology of micturation. Add a note on cystometrogram. Q. Describe the effects of complete transection of spinal cord. Q. What is muscle tone? Describe various mechanism involved in regulation of muscle tone. May/June 2011 Q. Describe ionic basis of nerve action potential. Q. Describe cystometrography. Q. Give the characteristic features of REM sleep; Write answer on narcolepsy. Q. Explain impedence matching by the ossicular system; What are the causes of conductive deafness? Q. Compare and contrast : Red muscle and white muscle isotonic and isometric contraction Q. Name all the plasma proteins; give their functions Q. Explain accommodation reflex of the eye. Q. Give the pathway of accommodation reflex. LAQ Q. Enumerate all ascending tracts. Describe the pathway for fine touch sensation. Add a note on Law of Projection. Q. WHat are the mechanisms to percieve color vision? Add a note on color blindness. Q. Describe in detail molecular basis of skeletal muscle contraction Nov/Dec 2011 Q. Secondary active transport. Q. Sarcotubular system Q. Descending pain inhibiting system. Q. Speech. Q. Draw and lebel Muscle spindle. What is its function? Q. Color Vison Q. CD4 Cells LAQ Q. Describe he role of middle ear and organ of corti in hearing. Q. Describe the functions of cerebellum. Q. Describe in detail functions of distal tubule in Kidney.

Nov/Dec 2012 Q. Draw and label muscle spindle. Q. What is glomerular filtration rate? Enumerate the factors affecting GFR. Q. Dark adaptation. Q. Referred pain. Q. Landsteiner's Law. What is the importance of Rh blood group? Q. REM sleep. Q. Refractory period. LAQ Q. Describe the mechanism of synaptic transmission and any two propertiesof synapse. Q. Describe the functions of cerbellum. Q. Describe the physiology of micturation in detail.

May/June 2013 Q. Define immunity; describe primary and secondary response and its role in vaccination. Q. Define homeostasis; Give characteristics of negetive feedback mechanism with example. Q. Define transport maximum; Describe mechanism of glucose reabsorption in renal tubules.

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190 Q. Trace the pathway of proprioceptive sensation from periphery to cortex.; What is sensory ataxia and how it differs from cerebellar ataxia? Q. What is place principle. Explain role of basilar membrane in perception of sound frequencies. Q. Define motor unit.; Desribe the factors regulating force of skeletal muscle contraction. Q. What is accomodation in eye? Describe accommodation reflex. State its significance. LAQ Q. Describe the connections and functions of basal ganglia. Describe the clinical features of parkinsonism. Q. Define GFR. Enumerate factors affecting GFR. Describe the regulation of GFR. Q. Draw a well lebelled diagram of neuromuscular junction. Describe the process of neuromuscular Transmission. What is myasthenia Gravis?

May/June 2014 Q. Mismatched Blood transfusion. Q. Parkinsonism. Q. Properties of Nerve fibers. Q. Functions of plasma proteins. Q. Osmosis. Q. Organ of Corti. Q. Role of kidney in acid base balance. LAQ Q. Define immunity. Give its classification. Write in detail about cell mediated immunity. Q. Define Resting membrane Potential. What are the factors contributing to the RMP? Write in detail about phases of action potential. Q. Enumerate functions of hypothalamus and explain any three functions in detail.

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STRUCTURE DICTATES

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JJ Notes Physiology - PDFCOFFEE.COM (2024)

References