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KIMS - Department of Physiology | Paper 1 - Third Internal Assessment

Complete Answer Guide

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LONG ESSAY (10 marks)

Q1. Describe the leads, waves and intervals of normal ECG. Mention the ECG changes in cardiac infarction.

A. LEADS OF ECG (12 leads total)

• Lead I: Right arm (-) to Left arm (+)
• Lead II: Right arm (-) to Left leg (+)
• Lead III: Left arm (-) to Left leg (+)

• aVR: Right arm
• aVL: Left arm
• aVF: Left foot

• V1: 4th intercostal space, right sternal border
• V2: 4th intercostal space, left sternal border
• V3: Between V2 and V4
• V4: 5th intercostal space, mid-clavicular line
• V5: Anterior axillary line (same horizontal level as V4)
• V6: Mid-axillary line (same horizontal level as V4-V5)

B. WAVES OF NORMAL ECG

• Q wave: First downward deflection (septal depolarization)
• R wave: First upward deflection
• S wave: Downward deflection after R

C. INTERVALS AND SEGMENTS

D. ECG CHANGES IN MYOCARDIAL INFARCTION

• Tall, peaked (hyperacute) T waves - earliest change
• ST segment elevation (> 1 mm in limb leads, > 2 mm in chest leads)

• ST elevation (STEMI pattern - "tombstone" or convex upward)
• Development of pathological Q waves (>0.04 s duration, >25% of R wave height)
• T wave inversion begins

• Pathological Q waves persist
• ST returns toward baseline
• Deep, symmetric T wave inversion (Wellens' sign pattern)

• Persistent pathological Q waves (permanent scar)
• ST normalizes
• T waves may normalize or remain inverted

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SHORT ANSWERS (3 marks each)

Q2. Explain why normally blood does not clot in vivo.

1. Smoothness of vascular endothelium: Intact endothelium does not activate factor XII (Hageman factor) - no trigger for intrinsic pathway.
2. Prostacyclin (PGI2): Released by endothelial cells; inhibits platelet aggregation and promotes vasodilation.
3. Antithrombin III (heparin cofactor): Neutralizes thrombin and several other activated clotting factors (Xa, IXa, XIa).
4. Thrombomodulin: Endothelial protein that binds thrombin; the complex activates Protein C.
5. Protein C and Protein S: Together inactivate Factor Va and Factor VIIIa.
6. Tissue Factor Pathway Inhibitor (TFPI): Inhibits the extrinsic pathway (Factor VIIa-tissue factor complex).
7. Natural heparin: Released by mast cells and basophils; enhances antithrombin III activity.
8. Fibrinolytic system (plasmin): Dissolves any small clots that form.
9. Blood flow: Continuously dilutes and removes activated clotting factors.

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Q3. Explain why cardiac muscle cannot be tetanised.

• The cardiac action potential lasts approximately 200-400 ms (compared to 1-2 ms in skeletal muscle).
• The absolute refractory period (ARP) of cardiac muscle lasts almost as long as the action potential itself - about 200-250 ms.
• This is due to the prolonged plateau phase (Phase 2) maintained by slow L-type Ca²+ channels remaining open.

• In skeletal muscle, the action potential is very short (1-2 ms), and tetanic contractions occur when stimuli arrive before relaxation is complete.
• In cardiac muscle, no new action potential can be generated during the absolute refractory period - so no second stimulus can cause sustained contraction during the contraction phase.
• By the time the ARP ends and the muscle is capable of responding again, the contraction is almost over and relaxation has begun.

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Q4. Why is the stool bulky and pale colored in obstructive jaundice?

• Bile salts and bilirubin cannot enter the small intestine.
• Normally, bilirubin is converted to urobilinogen (and then to stercobilin) by gut bacteria - stercobilin gives stool its normal brown color.
• In obstruction, no bilirubin reaches the gut, so no stercobilin is formed.
• Result: pale, clay-colored (acholic) stools.

• Bile salts are essential for fat emulsification and absorption in the small intestine.
• Without bile, dietary fats cannot be emulsified and are not absorbed by intestinal microvilli.
• Unabsorbed fats (especially long-chain triglycerides) pass into the stool.
• Fat in stool = steatorrhea - stool is pale, bulky, greasy, malodorous, and floats.

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Q5. Explain the cause for sigmoid shape of the Oxygen-Hemoglobin Dissociation Curve.

• Hb is a tetramer with 4 subunits (2α + 2β), each carrying one heme group.
• In the deoxy state (T form / tense form), the structure is tightly folded with low O2 affinity.

1. When the first O2 molecule binds to one heme group, it causes a conformational change in the globin subunit.
2. This change is transmitted to neighboring subunits via the 2,3-BPG binding site and salt bridges.
3. The molecule shifts from T-form (tense, low affinity) → R-form (relaxed, high affinity).
4. Each successive O2 molecule binds with increasing affinity (positive cooperativity).
5. The 4th O2 binds with the highest affinity.

• At low PO2 (tissues): Hb has low affinity → readily releases O2 (flat lower portion)
• At high PO2 (lungs): Hb has very high affinity → readily loads O2 (upper flat plateau)
• The steep middle portion allows efficient O2 delivery over a small PO2 range (20-60 mmHg)

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Q6. Explain the cause of negative resting membrane potential.

• K+ is ~30x more concentrated inside the cell (140 mEq/L inside vs. 4 mEq/L outside).
• Na+ is ~10x more concentrated outside (145 mEq/L outside vs. 10 mEq/L inside).
• Large organic anions (proteins, phosphates) are trapped inside and cannot cross the membrane.

• At rest, the membrane is highly permeable to K+ (via leak channels) and nearly impermeable to Na+.
• K+ flows out down its concentration gradient, leaving behind negative charges (organic anions) inside.
• This outward K+ current makes the inside more negative.
• K+ continues to leave until the electrical force (pulling K+ back in) equals the chemical force (driving K+ out) = K+ equilibrium potential (~-90 mV, Nernst equation).

• Pumps 3 Na+ out and 2 K+ in per cycle (electrogenic).
• Directly contributes about -5 to -10 mV to the RMP.
• More importantly, it maintains the ion concentration gradients.

• Impermeant intracellular anions attract cations inside and repel anions, contributing to the negative interior.

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SHORT ESSAY (5 marks each)

Q7. Explain the complications of blood transfusion.

• Delayed hemolytic reaction (3-14 days): Anamnestic antibody response in previously sensitized patients.
• Alloimmunization: Development of new antibodies against donor antigens.
• Graft-versus-host disease (GVHD): Donor lymphocytes attack immunocompromised recipient's tissues.
• Post-transfusion purpura: Thrombocytopenia 5-10 days post-transfusion.

• Hypocalcemia: Citrate (preservative) chelates Ca²+.
• Hyperkalemia: Stored blood has high K+ from hemolysis.
• Acidosis: Citric acid + lactic acid from stored blood.
• Coagulopathy: Dilution of clotting factors and platelets.

• HIV, Hepatitis B, Hepatitis C, CMV, malaria, syphilis (now rare due to screening).

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Q8. Define and classify shock. Explain hypovolemic shock.

• Baroreceptors detect fall in BP → sympathetic activation
• ↑ Heart rate, ↑ Contractility
• Vasoconstriction (arteriolar) → ↑ Peripheral resistance
• Renin-Angiotensin-Aldosterone system activated → Na+ and water retention
• ADH (Vasopressin) released → water reabsorption

• Tachycardia, anxiety, reduced pulse pressure, prolonged capillary refill
• Urine output decreases (20-30 mL/hr)

• Marked hypotension, tachycardia, confusion
• Oliguria (<20 mL/hr)

• Decompensated shock - all mechanisms fail
• Severe hypotension, unconsciousness, anuria
• Death if untreated

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Q9. Define Hypoxia. Explain different types of hypoxia with examples.

• PaO2 is reduced; hemoglobin is not fully saturated.
• Cause: Low inspired O2 tension (high altitude), hypoventilation (COPD, opioid overdose), diffusion impairment (pulmonary fibrosis, pneumonia), V/Q mismatch (pulmonary embolism), right-to-left shunt.
• Example: Mountain climbers at high altitude; drowning.

• PaO2 is normal but O2-carrying capacity of blood is reduced.
• Cause: Anemia (reduced Hb), carbon monoxide poisoning (COHb), methemoglobinemia.
• Example: CO poisoning - CO has 200x affinity for Hb over O2; patient looks "cherry red" but is hypoxic.

• Arterial O2 content is normal but blood flow is too slow to deliver adequate O2.
• Cause: Heart failure, shock, local arterial obstruction.
• Example: Congestive heart failure; gangrene of a limb.

• O2 delivery is normal but cells cannot utilize O2 due to impaired mitochondrial function.
• Cause: Cyanide poisoning (blocks cytochrome oxidase/Complex IV), alcohol in large doses.
• Example: Cyanide poisoning - blood and tissues are hyperoxic, but cells cannot use the O2.

• O2 delivery is normal but tissue demand exceeds supply.
• Example: Extreme exercise, high fever, thyrotoxicosis.

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Q10. Explain pathophysiology and management of peptic ulcer.

• H. pylori infection (90% of duodenal, 70% of gastric ulcers): Disrupts mucus layer, produces urease (generates NH3 → mucosal damage), stimulates gastrin release → ↑ HCl.
• Excess HCl secretion: Stimulated by gastrin, histamine, acetylcholine.
• NSAIDs/Aspirin: Inhibit COX-1 → ↓ prostaglandin synthesis → ↓ mucus and bicarbonate secretion, direct mucosal injury.
• Pepsin: Proteolytic enzyme activated at low pH.
• Bile reflux: Particularly in gastric ulcers.
• Smoking: ↓ prostaglandins, ↓ bicarbonate, ↑ gastric acid.

• Mucus-bicarbonate layer: Forms gel barrier trapping bicarbonate.
• Surface epithelial cells: Tight junctions prevent acid back-diffusion; rapid renewal.
• Prostaglandins (PGE2, PGI2): Stimulate mucus and bicarbonate, increase blood flow, promote cell renewal.
• Mucosal blood flow: Removes excess acid and delivers nutrients.
• Alkaline tide: Neutralizes residual acid.

• Eradicate H. pylori (Triple therapy): PPI (Omeprazole) + Amoxicillin + Clarithromycin for 14 days.
• Proton Pump Inhibitors (PPIs): Omeprazole, Pantoprazole - most effective acid suppressants (block H+/K+-ATPase pump).
• H2 receptor blockers: Ranitidine, Famotidine.
• Antacids: Symptomatic relief (Mg(OH)2, Al(OH)3).
• Cytoprotective agents: Sucralfate (forms gel at ulcer base), Misoprostol (PGE1 analog).

• Perforation: Emergency oversewing or patch repair.
• Bleeding: Endoscopic hemostasis; if fails - surgery.
• Vagotomy + drainage for refractory cases.

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SHORT ESSAY - 5 marks each (Q11-17)

Q11. Enumerate the steps of phagocytosis.

• Phagocytes are attracted to the site of infection by chemical signals (chemokines, complement C5a, bacterial products, LTB4).

• Phagocyte receptors bind to particles directly or via opsonins (IgG antibody, C3b complement).
• Receptors include: Fc receptors (for IgG), complement receptors (CR1, CR3), mannose receptors, scavenger receptors.
• Opsonization greatly enhances phagocytosis.

• Pseudopods extend around the particle ("zipper" mechanism).
• Plasma membrane folds around and encloses the particle in a membrane-bound vesicle called a phagosome.

• The phagosome fuses with lysosomes to form a phagolysosome.
• Lysosomal enzymes (acid hydrolases, lysozyme, myeloperoxidase, defensins) are released into the phagolysosome.

• NADPH oxidase converts O2 → superoxide (O2−) → hydrogen peroxide (H2O2).
• Myeloperoxidase converts H2O2 + Cl− → HOCl (hypochlorous acid) - most potent microbicidal agent.
• ROS (reactive oxygen species) damage microbial DNA, proteins, lipids.

• Lysozyme: Cleaves bacterial cell wall peptidoglycan.
• Defensins: Disrupt microbial membranes.
• Lactoferrin: Sequesters iron (essential for bacterial growth).
• Acid pH of phagolysosome.

• Debris is expelled by exocytosis (degranulation) or phagocyte undergoes apoptosis.

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Q12. Describe the factors regulating cardiac output.

• Normal CO = ~5 L/min (HR 72/min × SV 70 mL)

• Frank-Starling Law: As venous return increases → EDV increases → greater fiber stretch → greater force of contraction → ↑ SV.
• Factors increasing preload: ↑ venous return, ↑ blood volume, venoconstriction.

• ↑ afterload → ↓ SV (heart works harder to eject blood).
• Factors: hypertension, aortic stenosis.

• Intrinsic strength of contraction independent of preload.
• Increased by: sympathetic stimulation, catecholamines, digitalis, ↑ Ca²+, thyroid hormone.
• Decreased by: heart failure, hypoxia, acidosis, β-blockers.

• Metabolic autoregulation: ↑ tissue demand → local vasodilation → ↑ venous return → ↑ CO.
• Anemia, AV fistula: ↑ CO to compensate.

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Q13. Define GFR. Mention its normal value. Explain the factors regulating it.

• GFR is determined by the net filtration pressure (NFP):
  • NFP = Glomerular hydrostatic pressure (PGC, ~60 mmHg) - Bowman's capsule pressure (PBS, ~15 mmHg) - Oncotic pressure of plasma (πGC, ~32 mmHg)
  • NFP = 60 - 15 - 32 = +13 mmHg

• Myogenic mechanism: Increased arterial pressure → afferent arteriole constricts (prevents rise in PGC).
• Tubuloglomerular feedback (TGF): ↑ NaCl delivery to macula densa → adenosine release → afferent arteriole constriction → ↓ GFR (negative feedback).

• Dilation (prostaglandins, NO, dopamine) → ↑ PGC → ↑ GFR.
• Constriction (noradrenaline, angiotensin II, endothelin) → ↓ PGC → ↓ GFR.

• Constriction (angiotensin II mildly) → ↑ PGC → ↑ GFR (but severe constriction → ↓ GFR).

• ↑ Protein (dehydration, infusion) → ↑ πGC → ↓ GFR.
• ↓ Protein (nephrotic syndrome, malnutrition) → ↓ πGC → ↑ GFR.

• Determined by glomerular capillary permeability and surface area.
• ↑ Kf (glomerulonephritis, mesangial relaxation) → ↑ GFR.

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Q14. Describe the chemical regulation of respiration.

• Located in the ventral surface of medulla oblongata (separate from respiratory centers).
• Sensitive to ↑ PaCO2 (hypercapnia) and ↓ pH of CSF.
• Mechanism: CO2 crosses the blood-brain barrier → combines with H2O → H2CO3 → H+ + HCO3−. H+ ions stimulate chemoreceptors → ↑ ventilation.
• CO2 is the most important chemical regulator of respiration in normal conditions.
• Do NOT respond directly to O2 levels.

• Located in carotid bodies (at bifurcation of common carotid artery - most important) and aortic bodies (in aortic arch).
• Sensitive to: ↓ PaO2 (<60 mmHg), ↑ PaCO2, ↓ pH.
• Carotid bodies also respond to ↓ arterial blood flow, ↑ temperature.
• Signal via CN IX (Hering's nerve → glossopharyngeal) from carotid bodies and CN X (vagus) from aortic bodies.

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Q15. Describe composition and functions of Pancreatic juice.

• Volume: 1.5-2 L/day
• pH: 8.0-8.3 (alkaline)
• Produced by acinar cells (enzymes) and ductal cells (bicarbonate/water)

• Water: Major component
• Bicarbonate (HCO3−): Major anion; secreted in high concentrations (up to 140 mEq/L) by ductal cells in response to secretin; neutralizes gastric acid in duodenum.
• Electrolytes: Na+, K+, Cl−

• Trypsinogen → Trypsin (activated by enterokinase/enteropeptidase from duodenum)
• Chymotrypsinogen → Chymotrypsin (activated by trypsin)
• Proelastase → Elastase
• Procarboxypeptidase → Carboxypeptidase (cleaves C-terminal amino acids)
• Trypsin inhibitor (prevents autodigestion within pancreas)

• Pancreatic lipase: Hydrolyzes triglycerides → monoglycerides + fatty acids (requires co-lipase)
• Cholesterol esterase (CECE): Hydrolyzes cholesterol esters
• Phospholipase A2: Cleaves phospholipids

• Pancreatic α-amylase: Hydrolyzes starch → maltose, maltotriose, limit dextrins (secreted in active form)

• Ribonuclease (RNase) and DNase: Digest nucleic acids

1. Neutralizes gastric acid → creates optimal pH (7-8) for intestinal enzymes.
2. Protein digestion: Endopeptidases (trypsin, chymotrypsin) cleave interior peptide bonds; exopeptidases (carboxypeptidase) cleave terminal amino acids.
3. Fat digestion: Lipase and colipase hydrolyze triglycerides; bile salts emulsify fats first.
4. Carbohydrate digestion: Amylase completes starch digestion begun in the mouth.
5. Nucleic acid digestion: DNase and RNase.

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Q16. Describe micturition reflex. What is cystometrogram?

• Spinal micturition center: Sacral segments S2-S4 (detrusor nucleus / Onuf's nucleus)
• Higher centers: Pontine micturition center (PMC), hypothalamus, cortex (voluntary control)

1. Bladder filling: Urine accumulates; detrusor muscle remains relaxed (low pressure) due to sympathetic tone (β3 adrenoceptors). Internal urethral sphincter is closed (α1 sympathetic). External sphincter is closed (somatic, pudendal nerve).
2. Stretch stimulus: At ~300-400 mL, stretch receptors in the bladder wall send afferent impulses via pelvic nerve → S2-S4.
3. Micturition reflex arc:
   • Afferent: Pelvic nerve (sensory) from detrusor stretch receptors.
   • Integration: Sacral micturition center (S2-S4) coordinates with pontine micturition center.
   • Efferent:
     • Parasympathetic (pelvic nerve): Contracts detrusor (M3 receptors).
     • Sympathetic inhibited: Internal sphincter opens.
     • Somatic (pudendal nerve) inhibited: External sphincter relaxes (voluntary override can maintain contraction).
4. Voiding: Detrusor contracts, both sphincters relax → urine expelled.
5. After micturition: Sympathetic tone restores sphincter closure; detrusor relaxes; cycle restarts.

• Phase I (Filling / Tonus limb): Slight rise in pressure as bladder fills (0-300 mL). Bladder compliance is high (pressure remains nearly flat due to plastic nature of smooth muscle).
• First sensation to void: ~150-200 mL
• Phase II: Micturition contractions appear as pressure waves when the micturition reflex is triggered.
• Phase III (Voiding): Sharp rise in pressure during detrusor contraction, pressure falls after voiding.

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Q17. Enumerate the duties of a doctor.

• Provide competent medical care with compassion and respect for patient dignity.
• Maintain patient confidentiality (except where law requires disclosure).
• Obtain informed consent before any examination, investigation, or treatment.
• Provide emergency care when needed, regardless of payment.
• Not refuse treatment on grounds of race, religion, gender, or social status.
• Maintain continuity of care; not abandon a patient midway without notice.
• Refer to appropriate specialists when necessary.
• Truthfully inform patients about their condition and treatment options.

• Maintain the dignity and honour of the profession.
• Not indulge in self-advertisement or canvassing.
• Not poach patients from colleagues.
• Maintain proper medical records.
• Cooperate with medicolegal requirements and report notifiable diseases.
• Continue medical education (CME) to stay updated.

• Report communicable/notifiable diseases to public health authorities (e.g., cholera, plague, TB).
• Participate in health promotion and disease prevention.
• Provide impartial medicolegal services when required.
• Report cases of suspected child abuse, unnatural death, or injury due to crime.
• Respect the law and not prescribe controlled substances irresponsibly.

• Provide evidence in courts when summoned.
• Issue certificates (death, fitness, medical) honestly and accurately.
• Participate in national health programs.

• Maintain physical and mental health.
• Practice self-regulation and avoid substance abuse.
• Seek help if suffering from a condition that may impair professional duties.

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