Q.1. Enumerate the functions of cytoskeleton. Give a brief account of the structure of cell membrane.

(2 + 3 marks) Key: 1 Functions of cytoskeleton: 1. Cell support. (0.5 mark) 2. Shape of cell. (0.5 mark) 3. Motility within cytoplasmic matrix and circulation. (0.5 mark) 4. Microtubules take part in sensory transduction. (0.5 mark) Cell Membrane: The structure that separates the cell content from the external environment. Thin, pliable, elastic structure. It is 7.5-10 nanometers thick. Can be resolved only with electron microscope. (0.5 mark) Composed of proteins and lipids. Lipids are phospholipids and cholesterol. Lipid bilayer, 2 molecules thick. (0.5 mark) Bilayer is composed of phospholipid molecules. (0.5 mark) Each phospholipid molecule has a polar glycerol-phosphate head and is hydrophillic. (0.5 mark) Uncharged non-polar tail, made of two fatty acid chains and is hydrophobic. Polar heads are attracted to water so they lie on both inner and outer surfaces of membrane. (0.5 mark) Hydrophobic tails avoid water, so line up in the centre. So a sandwich like structure is formed, composed of two parallel sheets of phospholipid molecules lying tail to tail, with their polar heads exposed to water inside and outside the cell. (0.5 mark) -----------------------------------------------------------------------------------------------------------

Q.2 Which transport through the cell membrane shows Vmax? Compare properties of this transport with those of simple diffusion. (1+4) UHS MBBS (I) ANNUAL 2010, Q:1, Goal Ed. 2011 Key: 2 Reference: p 49, 50 Guyton 11th Ed. Vmax is the state of maximum rate of diffusion after which no further increase occurs is seen in facilitated diffusion.

Differences between Simple & Facilitated diffusion:

(Any 4 each = 4 marks)

Q.4 A 30 year old lady complains of diplopia, severe muscle weakness & fatigue. She also has drooping of eyelids & enlarged shadow of thymus on ultrasound. a. What can be the possible diagnosis? b. What is the physiologic basis of this pathology? c. What positive findings do you expect in her serum examination? d. What medicine can alleviate the ladys complaints? (1+2+1+1)

UHS MBBS (I) ANNUAL 2009, Q:8, Goal Ed. 2011 Key: 4 Reference: p 89, Guyton 11th Ed. a. MYASTHENIA GRAVIS (1 mark)

b. A rare auto-immune disease. Irreversible damage to acetylcholine receptors at motor end plate, though acetylcholine is normally released. Voltage of EPP is very low (Miniature EPP), so action potential is not followed. At rest normally, a few synaptic vesicles break to liberate Ach from synaptic vesicles leading to small change in EPP (about 0.5 mV) called MEPP. Impulse fails to transmit through NMJ resulting into Severe muscle weakness & fatigue (Extra-ocular muscles: ptosis, diplopia), difficulty in Swallowing, weakness of Respiratory and Facial muscles) (2 marks)

c. AUTO-ANTIBODIES against acetylcholine gated receptor channels. (1 mark) d. ANTICHOLINE ESTERASES (Neostigmine or Physostigmine). These inhibit enzyme acetylcholine esterase. As a result acetylcholine is not hydrolyzed & more acetylcholine available for available number of receptors. (1 mark)

Q.3 How action potential propagates along a myelinated & unmyelinated nerve fiber? What are advantages of myelinated type of propagation? (5) UHS BDS SUPPLEMENTARY 2008, Q:2, Goal Ed. 2011 Key: 3 Reference: p 68, 69 Guyton 11th Ed. MYELINATED: Propagation of action potential along a myelinated nerve fiber is by Saltatory conduction, i-e., jumping of action potential from one node to the next node of Ranvier. (1) Local circuit of current is completed between depolarized node & adjacent polarized node. The current flowing out through the polarized node activates sodium channels. (0.5)

Diagram: 0.5

ADVANTAGES OF MYELINATED: i. Increased velocity of conduction. A-alpha fibers have largest conduction velocity of 70-120 meters/sec. ii. Less expenditure of energy. iii. Provision of insulation & 50-fold decrease in membrane capacitance allow repolarization with very little transfer of ions.

(0.5+0.5+0.5) UNMYELINATED: Propagation of action potential along an unmyelinated nerve fiber is by point to point conduction, i-e., action potential propagates at every point even in the area in-between the nodes. This type of propagation is slower, uses more energy & does not offer insulation. (1)

Diagram: (0.5)

Q.11 A newborn baby develops deep yellow colour of skin and eyes within 24 hours after birth. His blood group is O +ve. Blood picture shows many erythroblasts in blood. a) What is the problem in the new born and why? marks) b) What other investigations would you like to do? marks) c) How will you manage the baby? Key: 11 a) What is the problem in newborn & why? The problem is Erythroblastosis fetalis. (1 mark) In this case, the mother is Rh negative & the father and baby are Rh positive, as the baby has inherited Rh positive antigen from his father. (0.25 mark) Mother develops anti-Rh antibodies / agglutinins from exposure to Rh antigen of fetus. (0.25 mark) (1+1 (2 (1 mark)

(1+1 marks)

Mothers Rh antibodies (IgG) pass through placenta into the fetal blood (0.25 mark) RBC agglutination / destruction leads to jaundice of newborn (0.25 mark)

b) Investigations: each) i) ii) i) ii) Blood grouping of mother. Hb % Serum bilirubin Serum IgG

(0.5 marks

c) Management of baby: (1 mark) Exchange transfusion: Rh positive blood of newborn will be replaced with Rh negative blood, (0.25 mark) equal to 400 ml, (0.25 mark) over a period of 1.5 or more hours, (0.25 mark) while Rh positive blood of neonate is being removed. mark) (0.25

Q10. When blood without an anticoagulant is taken in a glass tube it clots. Give mechanisms of this blood clotting. (5) Key:10 INITIATION OF BLOOD CLOTTING BY INTRINSIC PATHWAY: When blood comes into contact with a wettable surface it leads to activation of intrinsic pathway of coagulation. This pathway involves the following sequence of events: Contact of blood with glass causes a conformational change in the factor XII causing it to become activated ( aXII) aXII acts enzymatically in the presence of HMW kininogen, on Factor XI activating it (aXI) Factor aXI acts on Factor IX activating it (aIX) aIX acts in concert with factor VIII , platelet phospholipids and Ca++ to activate Factor X (aX) After this step the rest of the steps are common for extrinsic and intrinsic pathways. aX combines with Factor V and platelet or tissue phospholipids to form the complex called prothrombin activator. Prothrombin acts in seconds to cleave prothrombin (a plasma protein) forming thrombin Thrombin finally acts on fibrinogen forming fibrin which has the capability to polymerize with other fibrin molecules to form fibrin fibers. It also activates fibrin stabilizing factor which causes multiple cross linkages between fibrin fibers strengthening the fibrin meshwork. Within a few minutes of formation of clot, which is composed of a meshwork of fibrin fibers, platelets , blood cells and plasma, it begins to contract and usually expresses most of the fluid from the clot. INTRINSIC PATHWAY OF COAGULATION:

Q5. Define cardiac cycle? What are pressure changes which occur in left ventricle during it? (3) Cardiac cycle: The cardiac events that occur from the beginning of one heart beat to the beginning of the next are called the cardiac cycle. Pressure changes in left ventricle in different phases of cardiac cycle can be summarized according to different phases of cardiac cycle. 1.Phase of Isovolumic contraction of ventricle: During this phase there is rapid increase in ventricular pressure up to 80 mmHg. 2. Phase of Ejection: Phase of Rapid Ejection: There is a further increase in ventricular pressure that reaches maximum up to 120mm Hg Phase of Reduced ejection: Pressure falls reaching the level of aortic pressure or slightly less than that Aortic valve closes 3. Phase of Isovolumic relaxation: Rapid fall in ventricular pressure to diastolic pressure level Opening of AV valves 4. Period of filling: Phase of Rapid Inflow: There is no change in ventricular pressure Phase of Diastasis or slow inflow: There is no change in ventricular pressure Last rapid inflow phase or Atrial Systole: Very slight or modest increase in ventricular pressure AV valves close

Q9. a) Draw and label oxygen-hemoglobin dissociation curve (2) b) What are the factors which will shift the curve right? (1) c) Briefly discuss the Haldane effect (2)

Key 9. (p506, 508, 511 Guyton 11th Ed) a) (2 marks)

a) Factors shifting to right: 1. Increase hydrogen ion 2. Increase carbon dioxide 3. Increased temperature 4. Increased 2,3 BPG

(0.25) (0.25) (0.25) (0.25)

b) The Haldane effect Binding of oxygen with hemoglobin tends to displace carbon dioxide from the blood. (0.5)

The Haldane effect results from the simple fact that the combination of oxygen with hemoglobin in the lungs causes the hemoglobin to become a stronger acid. (0.5) This displaces carbon dioxide from the blood and into the alveoli in two ways: (1) The more highly acidic hemoglobin has fewer tendencies to combine with carbon dioxide to form carbaminohemoglobin, thus displacing much of the carbon dioxide that is present in the carbamino form from the blood. (0.5) (2) The increased acidity of the hemoglobin also causes it to release an excess of hydrogen ions, and these bind with bicarbonate ions to form carbonic acid; this then dissociates into water and carbon dioxide, and the carbon dioxide is released from the blood into the alveoli and, finally into the air. (0.5)

Q8. A 25 years old deep sea diver receives a laceration on his leg under water. He rapidly ascends to the surface to get First Aid. He develops dyspnea, shortness of breath, retro-sternal chest pain along with painful legs and arms which becomes worse with movement. a) What is he suffering from? (1) b) Give pathophysiology of his disease (3) c) Give his treatment (1) Key 8 (p548 Guyton 11th Ed) a) Decompression sickness or Caisson disease or Driver paralysis or Dysbarism (1) b) The quantity of Nitrogen in the body fluids and tissues depends on partial pressure of nitrogen in alveolar air and its solubility in the fluid. It increases in case of deep sea divers who breathe air at very high partial pressures this increase amount of nitrogen under high pressures dissolves in nerve tissue and under rapid ascent , the gas being inert cannot be utilized by the tissues, gas bubbles are formed in the blood (1) These bubbles accumulated around nerves & joints & caused pain (bends) (1) Bubbles around pulmonary vessels lead to dyspnea, choaks (shortness of (1) (1)

breath)

c) Hyperbaric oxygen therapy

Q.7Outline the special features of circulation of coronary vessels. (5 marks) Key22 SPECIAL FEATURES: Blood flow through Rt.coronary artery is pre-dominant in 50% of humans. Blood flow through Lt.coronary artery is pre-dominant in 20% of humans. Blood flow through both coronaries is equal in 30% of humans. (0.5 mark) Coronary blood flow at rest is 225-250ml/min. It may increase 4-6 times during exercise. (0.5 mark) Myocardial O2 consumption at rest is about 8ml/100g/min. mark) (0.5

coronary blood flow varies with phases of cardiac cycle. More than 70% coronary blood flow occurs during diastole During systole the blood flow decreases due to compression by cardiac muscle. (0.5 mark) Subendocardial vessels are compressed much more than epicardial vessels. So subendocardial portion of myocardium is more prone to ischemia. It is the most common site of M.I. (0.5 mark) Br.of Lt.coronary art. are compressed more in systole than branches of the Rt.coronary Blood flow through coronary sinus increases in systole. (0.5 mark) Collaterals are important in coronary circulation. In gradual narrowing of coronary artery, collaterals open up to compensate. (0.5 mark)

Coronary blood flow is autoregulated according to O2 consumption & demand. When PO2 in myocardium fallshypoxia (due to increased consumption) (0.5 mark) Direct effect of sympathetic stimulation on coronary vessels: Coronary vasoconstriction. Indirect effect: (more important) Coronary vasodilation with more coronary blood flow. Symp. Stim. As a result More heart rate & contractility leads to More myocardial metabolism & O2 consumption leads to hypoxia vasodilator metabolites leads to Vasodilitation (0.5 mark) Direct effect of parasymp. Stim.: coronary vasodilation Indirect effect: coronary vasoconstriction with decreased coronary blood flow. Parasymp. Stim. leads to Decreased heart rate & Force of contraction as a result less myocardial metabolism & O2 consumption no hypoxia no release of vasodilator metabolites as a result there is Vasoconstriction. (0.5 mark)

Q.6 A 32 years old lady, Safia was brought semiconscious to the emergency of hospital with a history of induced abortion by a nurse at home. On examination her body temperature was 102 F, pulse was very rapid and feeble and BP was 60/50mmHg. a. What is the most likely diagnosis? b. Briefly mention the special features of her disease. (1+4 marks) key:6 a. Septic shock b. 1. High fever 2. Marked Vasodilitation in infected tissues. (1 mark) (1 mark) (1 mark)

3. May be high Cardiac output due to arteriolar dilation in infected tissues & by high metabolic rate and V.D elsewhere in the body due to bacterial toxin stimulation of cellular metabolism & from high body temperature. (0.5 mark) 4. Sludging of blood due to red cell agglutination in response to degenerating tissues. (0.5 mark) 5. Micro-blood clot development in widespread areas of body (DIC) clotting factors are used up multiple tissue hemmorhages, mainly in GIT. (1 mark) Q.12 Write short notes on: a. Heat Stroke b. Frost-bite marks)

(2.5+2.5

HEAT STROKE: Upper limit of air temp that can be tolerated depends on whether air is dry or wet. (0.25 mark)

 If dry air with convection currents, evaporation can take place & one can withstand even 103 F temp for several hrs. (0.25 mark) If air has 100% humidity or if body is in water then body temp. begins to rise, whenever environmental temp rises above about 94 F. (0.25 mark) If person is performing heavy work heatstroke may occur at an environmental temp. above 85-90 F. (0.25 mark) When body temp. rises beyond a critical temp. (105 - 108 F), heatstroke is likely to occur. (0.25 mark) Symptoms of heatstroke are aggravated by a degree of circulatory shock due to excessive loss of fluid & electrolytes in sweat. (0.25 mark) Hyperpyrexia is damaging to body tissues (mainly brain). (0.25 mark) Even few min. of very high body temp. may be fatal. (0.25 mark) Treatment of heatstroke: Immediately placing the person in cold water bath causes uncontrollable shivering leading to increase in rate of heat production. (0.25 mark) OR Sponge or spray cooling of the skin, rapidly decreases body core temp. (0.25 mark) FROST BITE: Extreme low temp. exposure causes the surface areas to freeze. This is called frostbite. (0.5 mark) Commonly seen in lobes of ears & digits of hands & feet. (0.5 mark) If ice crystals are formed in the cells, they may cause permanent damage (circulatory impairment & local tissue damage). (1 mark) On Thawing, there may be gangrene formation, leading to surgical removal of frostbitten areas. (0.5 mark)