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AIIMS Rajkot - 1st MBBS Physiology Paper II - Complete Answers

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SECTION A

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Q.1 - Clinical Case: 55-year-old male with chest pain

(a) Most Probable Diagnosis (1 mark)

• Squeezing central chest pain radiating to left arm = classic anginal pain
• Nausea, sweating, diaphoresis = autonomic features of MI
• Risk factors: smoking, hypertension, sedentary lifestyle
• BP 160/100 mmHg, HR 90 bpm (tachycardia), RR 20/min (tachypnoea)

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(b) Different ECG Waves with respect to Phases of Action Potential in Cardiac Muscle (5 marks)

The Cardiac Action Potential (Ventricular Muscle)

Correlation of ECG Waves with Action Potential Phases:

ACTION POTENTIAL:                ECG:
Phase 4 (rest) ────────────────→ Isoelectric line (TP segment)
Phase 0 (depolarization) ──────→ QRS complex (ventricular depolarization)
Phase 2 (plateau) ─────────────→ ST segment (isoelectric normally)
Phase 3 (repolarization) ──────→ T wave (ventricular repolarization)

Atrial depolarization ─────────→ P wave
Atrial repolarization ─────────→ Hidden within QRS (Ta wave)
AV nodal delay ────────────────→ PR interval

Normal ECG Waves and Intervals:

• P wave: Atrial depolarization (0.08-0.1 s, amplitude <0.25 mV)
• PR interval: Conduction time from SA node to ventricle (0.12-0.20 s); represents delay at AV node
• QRS complex: Ventricular depolarization (0.06-0.10 s); corresponds to Phase 0 of action potential
• ST segment: Corresponds to Phase 2 (plateau) - all ventricular cells depolarized; isoelectric normally
• T wave: Ventricular repolarization (Phase 3); normally upright in most leads
• QT interval: Total ventricular electrical activity (0.35-0.44 s)
• U wave: Repolarization of Purkinje fibers or papillary muscles

Diagram Description:

Cardiac Action Potential (Ventricular muscle):
mV
+30 |    Phase 1
    |   /‾‾‾‾‾‾‾‾‾\ Phase 2 (Plateau)
    |  /            \_______________
0   | /                              \
    |/  Phase 0                       \  Phase 3
-90 |Phase 4 (RMP)                     \_________Phase 4

ECG below it:
P wave → QRS → ST segment → T wave

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(c) Inferior Wall MI - ECG Findings and Leads (2+2 = 4 marks)

ECG Findings in Inferior Wall MI:

• ST elevation (>1 mm) in inferior leads
• Tall, peaked (hyperacute) T waves initially

• Pathological Q waves (>0.04 s wide, >25% depth of R wave) - indicates transmural necrosis
• ST elevation with coved/convex shape
• T wave inversion

• ST depression in leads I, aVL (high lateral leads)

Which Leads are Prominent in Inferior Wall MI:

• Right ventricular MI can occur simultaneously (look for ST elevation in V4R)
• AV block is common (RCA supplies AV node)
• Bradycardia may occur (vagal activation)

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Q.2 - Short Notes (5×4 = 20 marks)

Q.2A - Role of RAAS in Blood Pressure Regulation (5 marks)

Trigger for RAAS Activation:

1. Decreased renal perfusion pressure (sensed by JG cells)
2. Decreased Na⁺ delivery to macula densa
3. Sympathetic stimulation (β1 receptors on JG cells)
4. Decreased circulating blood volume

Steps in RAAS:

↓ Renal Perfusion / ↓ NaCl to macula densa / ↑ Sympathetic activity
                              ↓
        JG cells of afferent arteriole release RENIN
                              ↓
    Renin cleaves Angiotensinogen (liver) → ANGIOTENSIN I (10 AA)
                              ↓
    ACE (Angiotensin Converting Enzyme - mainly in lung)
                              ↓
                    ANGIOTENSIN II (8 AA)
                    ↙           ↓           ↘
          Adrenal             Brain          Blood vessels /
          Cortex              (thirst,        Kidney
            ↓                 ADH release)      ↓
        ALDOSTERONE              ↓          Vasoconstriction
            ↓               ↑ water         ↑ BP directly
    ↑ Na⁺ reabsorption      intake          ↑ GFR
    ↑ K⁺ excretion                         Na⁺/H₂O reabsorption
    (DCT/collecting duct)
            ↓
    ↑ ECF volume → ↑ BP

Actions of Angiotensin II:

1. Vasoconstriction - most powerful vasoconstrictor known; acts on AT1 receptors
2. Aldosterone release - from zona glomerulosa of adrenal cortex
3. ADH (vasopressin) release - from posterior pituitary
4. Stimulates thirst - via hypothalamic centers
5. Directly acts on renal tubules - increases Na⁺/H₂O reabsorption
6. Preferential constriction of efferent arteriole - maintains GFR despite reduced renal perfusion
7. Central sympathetic stimulation

Net Result:

• ↑ Na⁺ and H₂O retention → ↑ Blood volume → ↑ Cardiac output → ↑ BP
• Direct vasoconstriction → ↑ TPR → ↑ BP
• Negative feedback: ↑ BP → ↓ renin secretion (pressure natriuresis)

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Q.2B - Flowchart: Intrinsic and Extrinsic Pathway of Blood Coagulation (5 marks)

EXTRINSIC PATHWAY              INTRINSIC PATHWAY
(triggered by tissue injury)   (triggered by contact activation)

Tissue Factor (TF/III)         XII → XIIa (contact with collagen/glass)
+ Factor VII                        ↓
        ↓                      XI → XIa
    TF-VIIa complex                 ↓ (Ca²⁺)
        ↓                      IX → IXa
        ↓                           ↓
        ↓        ←— (IXa + VIIIa + Ca²⁺ + PL = Tenase complex)
        ↓                           ↓
        └────────────────────────────┘
                      ↓
              X → Xa  (COMMON PATHWAY)
                      ↓
          (Xa + Va + Ca²⁺ + PL = Prothrombinase complex)
                      ↓
          Prothrombin (II) → Thrombin (IIa)
                      ↓
          Fibrinogen (I) → Fibrin (Ia) [soluble]
                      ↓  (XIII → XIIIa by thrombin)
          Cross-linked Fibrin (stable, insoluble clot)

Key Points:

• Extrinsic pathway is faster (seconds) - tested by PT (Prothrombin Time)
• Intrinsic pathway is slower (minutes) - tested by aPTT (activated Partial Thromboplastin Time)
• Both converge at Factor X - Common Pathway
• Vitamin K-dependent factors: II, VII, IX, X (and Protein C, S)
• Calcium (Factor IV) is required in almost all steps
• Thrombin is the key enzyme: activates factors I, V, VIII, XIII, and platelets

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Q.2C - Counter Current Multiplier in Kidney (5 marks)

Location: Loop of Henle (mainly in juxtamedullary nephrons)

Basic Principle:

Properties of the Two Limbs:

Mechanism (Single Effect Multiplied):

1. The thick ascending limb actively pumps NaCl into the medullary interstitium (impermeable to water, so water stays in tubule) → This creates local osmotic gradient of ~200 mOsm/L
2. The high medullary osmolarity draws water out of the descending limb (which is water-permeable) → tubular fluid in descending limb becomes progressively concentrated as it descends
3. This concentrated fluid then enters the ascending limb, providing more NaCl to be pumped out
4. This process is multiplied as fluid flows down then up, creating a gradient from ~300 mOsm/L at cortico-medullary junction to ~1200 mOsm/L at the tip of the papilla
5. Urea also contributes to medullary hyperosmolarity (urea recycling in inner medulla via UT-A1/UT-A3 transporters)

Role of Vasa Recta:

Significance:

• Enables production of urine up to 1200-1400 mOsm/L (4x plasma osmolarity)
• ADH acts on collecting duct (made permeable to water) to utilize this gradient
• Without ADH → dilute urine; With ADH → concentrated urine (up to 1200 mOsm/L)

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Q.2D - Define Shock. Explain the Distributive Types of Shock (5 marks)

Definition of Shock:

Classification of Shock:

Distributive Types of Shock:

• Cause: gram-negative bacteria (endotoxin/LPS) or gram-positive organisms
• Pathophysiology:
  • LPS → macrophage activation → TNF-α, IL-1, IL-6
  • Massive release of nitric oxide (NO) → widespread vasodilation
  • ↓ TPR → ↓ BP despite ↑ CO (hyperdynamic state initially)
  • Increased vascular permeability → fluid leaks out → effective hypovolemia
  • Later: myocardial depression, hypodynamic state
• Features: fever, warm skin, bounding pulse, high CO, low SVR, lactic acidosis

• Cause: Type I hypersensitivity reaction (penicillin, bee sting, nuts)
• Pathophysiology:
  • IgE on mast cells → antigen binding → massive degranulation
  • Histamine, leukotrienes, prostaglandins → widespread vasodilation
  • ↑ Vascular permeability → ↓ effective circulating volume
  • Bronchospasm → respiratory distress
• Features: urticaria, angioedema, hypotension, bronchospasm
• Treatment: Adrenaline (epinephrine) IM is first-line

• Cause: High spinal cord injury (above T6), spinal anesthesia
• Pathophysiology:
  • Loss of sympathetic tone below the level of injury
  • Massive vasodilation of blood vessels (loss of vasomotor control)
  • Bradycardia (unopposed vagal tone) - unlike other shocks where HR increases
• Features: hypotension, bradycardia, warm dry skin (paradoxical)
• Spinal shock vs neurogenic shock: Spinal shock = loss of reflexes; Neurogenic shock = hemodynamic instability

• Caused by bacterial superantigens (Staph. aureus TSST-1, Strep. pyogenes)
• Massive T-cell activation → cytokine storm → distributive shock

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Q.3 - Short Answer Questions (4×2 = 8 marks)

Q.3A - Role of Neutrophils in Immune Response (2 marks)

1. Chemotaxis - migrate to site of infection guided by chemokines (IL-8, C5a, LTB4, fMLP)
2. Phagocytosis - engulf bacteria via FcR (IgG-coated) and CR3 (C3b-coated pathogens) - opsonization enhances this
3. Killing mechanisms:
   • Oxidative burst (respiratory burst): NADPH oxidase generates superoxide (O₂⁻) → H₂O₂ → hypochlorite (HOCl via myeloperoxidase) - highly bactericidal
   • Non-oxidative: lysozyme, defensins, elastase, lactoferrin in granules
4. NET formation (Neutrophil Extracellular Traps): Chromatin + granule proteins released extracellularly to trap and kill bacteria
5. Release of cytokines: IL-1, TNF-α, IL-12 to amplify inflammation
6. Short-lived: survive only 6-8 hours in circulation; 1-2 days at tissue sites; then undergo apoptosis (phagocytosed by macrophages)

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Q.3B - Pathophysiological Basis of Erythroblastosis Foetalis (2 marks)

Pathophysiology:

1. Rh-negative mother carries Rh-positive fetus (inherited from Rh+ father)
2. At delivery (or abortion/amniocentesis), fetal Rh+ RBCs enter maternal circulation → fetomaternal hemorrhage
3. Maternal immune system is sensitized → forms anti-Rh (anti-D) IgG antibodies
4. First pregnancy: usually unaffected (sensitization only)

Consequences:

• Anemia → hydrops fetalis (severe edema from hypoproteinemia + cardiac failure)
• Jaundice (hyperbilirubinemia - unconjugated bilirubin)
• Kernicterus (bilirubin deposits in basal ganglia - brain damage) in neonates
• Hepatosplenomegaly (extramedullary hematopoiesis)

Prevention: Anti-D immunoglobulin (Rho-GAM) given to Rh- mother at 28 weeks and within 72 hours of delivery to prevent sensitization

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Q.3C - Cushing's Reflex (2 marks)

Trigger:

• Severe rise in ICP (e.g., brain tumor, hemorrhage, trauma) → cerebral ischemia → CO₂ buildup in vasomotor center (VMC) of medulla

Mechanism:

1. ↑ ICP → cerebral blood flow compromised → local hypercapnia and acidosis in VMC
2. VMC strongly activated → massive sympathetic discharge
3. → Marked hypertension (systolic BP may rise to 200-250 mmHg)
4. Severe hypertension → baroreceptor-mediated bradycardia (reflex slowing)
5. Also: slow, irregular respirations (Cheyne-Stokes or Kussmaul pattern)

Cushing's Triad (classic):

• Hypertension (wide pulse pressure)
• Bradycardia
• Irregular respirations

Significance:

• It is a late, ominous sign of raised ICP - indicates brainstem compression
• The hypertension "pushes" blood through the brain against the elevated ICP, maintaining CPP
• CPP = MAP - ICP (Cushing reflex tries to maintain CPP > 60 mmHg)
• Clinically: sign of impending brain herniation - requires immediate intervention

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Q.3D - Wenckebach Phenomenon in Heart Block (2 marks)

Definition:

Mechanism:

• Located at the AV node level (nodal block)
• Each successive impulse finds the AV node relatively refractory, so conduction takes progressively longer
• Eventually one impulse fails to conduct → the AV node has a full recovery period → next impulse conducts with short PR → cycle repeats

ECG Features:

1. Progressive prolongation of PR interval in each beat
2. Sudden dropped QRS (non-conducted P wave)
3. RR interval progressively shortens before the drop (because each increment of PR lengthening decreases)
4. After the dropped beat, PR interval resets to its shortest value
5. Pattern: 3:2 or 4:3 or 5:4 (P:QRS ratio)

P P P P (4 P waves) → 3 QRS complexes (4th P dropped)
PR: 0.16 → 0.22 → 0.28 → (no QRS) → 0.16 → repeats

Clinical Significance:

• Usually benign, especially in athletes or with inferior MI (RCA occlusion affecting AV node)
• Often reversible (vagal in origin or during sleep)
• Rarely progresses to complete heart block
• Contrast with Mobitz Type II (fixed PR, sudden drop) - which is more serious and may need pacemaker

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SECTION B

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Q.4 - Neural Regulation of Respiration + Cheyne-Stokes + Kussmaul's Breathing (6+3 = 9 marks)

Neural Regulation of Respiration (6 marks)

A. Respiratory Centers

• Located in the nucleus tractus solitarius (NTS) of dorsal medulla
• Contains primarily inspiratory neurons
• Generates basic inspiratory rhythm
• Receives input from peripheral chemoreceptors and lung stretch receptors (via vagus)
• Sends impulses to phrenic nerve (C3,4,5) → diaphragm, and to external intercostal muscles

• Located in the nucleus ambiguus and nucleus retroambiguus of ventral medulla
• Contains both inspiratory and expiratory neurons
• Normally quiet during quiet breathing
• Active during forced breathing (exercise, hyperpnea)
• Controls expiratory muscles (internal intercostals, abdominal muscles)
• Pre-Botzinger complex (within VRG) - the main pacemaker of respiratory rhythm

• Located in the upper pons (nucleus parabrachialis medialis + Kolliker-Fuse nucleus)
• Limits inspiration - turns off inspiratory neurons (prevents apneusis)
• Controls rate and depth of breathing
• Sends continuous inhibitory signals to DRG
• Ablation → apneusis (prolonged inspiratory gasps)

• Located in the lower pons
• Tends to prolong inspiration (sustains inspiratory drive)
• Normally inhibited by the pneumotaxic center
• If pneumotaxic center is damaged → apneustic breathing (prolonged gasps with brief expirations)

B. Mechanism of Normal Quiet Breathing

Pre-Botzinger complex (VRG) generates rhythmic impulses
                    ↓
DRG inspiratory neurons fire → phrenic nerve + external intercostals
                    ↓
Diaphragm contracts → thorax expands → ↓ intrapleural pressure
                    ↓
Lungs expand → stretch receptors (Hering-Breuer reflex via vagus)
                    ↓
Stretch receptor input → inhibits DRG + activates pneumotaxic center
                    ↓
Inspiratory neurons stop firing → diaphragm relaxes → passive expiration

C. Hering-Breuer Reflex:

• Lung stretch receptors (slowly adapting, in airway smooth muscle) → via vagus → inhibit further inspiration when lungs are sufficiently inflated
• Acts as a feedback brake preventing over-inflation
• More important in infants; less significant in quiet adult breathing

D. Chemical Control:

• Central chemoreceptors (medulla, ventral surface): respond mainly to ↑ PCO₂/H⁺ in CSF - most important for day-to-day control
• Peripheral chemoreceptors (carotid and aortic bodies): respond to ↓ PO₂ (< 60 mmHg), ↑ PCO₂, ↑ H⁺ - hypoxic drive

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Cheyne-Stokes Breathing (1.5 marks)

Apnea → Gradual ↑ depth of breathing → Peak → Gradual ↓ depth → Apnea → (cycle repeats every 30-60 seconds)

1. Underlying condition (e.g., cardiac failure, CNS disease) causes prolonged circulation time between lungs and brain chemoreceptors
2. During apnea: CO₂ builds up, O₂ falls → eventually reaches threshold → chemoreceptors trigger hyperventilation
3. During hyperventilation: CO₂ is blown off, O₂ rises → chemoreceptors inhibited → apnea occurs again
4. The feedback loop is delayed (due to long circulatory transit time) → oscillation

• Congestive cardiac failure (most common)
• Stroke, brain injury, uremia
• Normal in premature infants and some normal persons at high altitude or during deep sleep

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Kussmaul's Breathing (1.5 marks)

• Severe metabolic acidosis → ↓ blood pH → stimulates peripheral chemoreceptors (carotid bodies) and central chemoreceptors intensely
• Results in maximal hyperventilation to blow off CO₂ as respiratory compensation
• This is a compensatory mechanism: CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻ (↓ CO₂ reduces H⁺ production)

• Diabetic ketoacidosis (DKA) - most classic cause
• Severe renal failure (uremic acidosis)
• Severe diarrhea with bicarbonate loss
• Lactic acidosis, methanol/salicylate poisoning

• Kussmaul: deep, regular, fast - due to metabolic acidosis
• Cheyne-Stokes: waxing-waning with apnea - due to CNS disease or heart failure

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Q.5 - Short Notes (4×5 = 20 marks)

Q.5A - HCl Secretion in Stomach (5 marks)

Stimulants of HCl Secretion:

1. Acetylcholine (ACh) - via muscarinic M3 receptors → ↑ IP₃/Ca²⁺ → activates H⁺/K⁺ ATPase
2. Histamine - from ECL (enterochromaffin-like) cells → H₂ receptors → ↑ cAMP/PKA → activates H⁺/K⁺ ATPase
3. Gastrin - from G cells (antrum) → CCK-B receptors → ↑ Ca²⁺ → activates H⁺/K⁺ ATPase

Mechanism at Cellular Level:

• H⁺ pumped into stomach lumen via H⁺/K⁺ ATPase (proton pump) on canalicular membrane
• K⁺ enters cell in exchange

• Cl⁻ enters parietal cell from blood via Cl⁻/HCO₃⁻ exchanger on basolateral membrane
• HCO₃⁻ exits into blood → "alkaline tide" in blood after meal
• Cl⁻ exits into stomach lumen via CFTR/Cl⁻ channels

Phases of Gastric Acid Secretion:

Inhibitors of HCl Secretion:

• Secretin - from S cells (duodenum) when acid enters duodenum
• GIP (Gastric Inhibitory Peptide) - from K cells
• Somatostatin - from D cells; inhibits G cells, ECL cells, and parietal cells
• Low pH (<2) - direct inhibition (negative feedback)
• High fat, hypertonic chyme in duodenum

Clinical Relevance:

• Proton pump inhibitors (PPIs) - omeprazole, pantoprazole → block H⁺/K⁺ ATPase irreversibly → used in peptic ulcer, GERD
• H₂ blockers - ranitidine → block H₂ receptors on parietal cells

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Q.5B - Phases of Deglutition (Swallowing) (5 marks)

Phase 1: Oral (Voluntary) Phase

• Duration: 1-2 seconds
• Control: Voluntary (cerebral cortex)
• Events:
  1. Food is chewed and mixed with saliva to form a bolus
  2. Tongue pushes bolus posteriorly against the hard palate
  3. Tongue tip is elevated → bolus moved to posterior pharynx
  4. Initiation of the swallowing reflex once bolus reaches faucial pillars
• Once initiated, further swallowing is involuntary and cannot be stopped

Phase 2: Pharyngeal (Involuntary) Phase

• Duration: ~1 second
• Control: Swallowing center in medulla/lower pons (nucleus tractus solitarius + nucleus ambiguus)
• Events (precisely coordinated - "swallowing apnea"):
  1. Soft palate elevates → closes nasopharynx (prevents nasal regurgitation)
  2. Palatopharyngeal folds approximate → narrow the passage so only small bolus can pass
  3. Vocal cords adduct (close) → larynx elevates and moves anteriorly under epiglottis
  4. Epiglottis tips posteriorly → covers laryngeal inlet (prevents aspiration)
  5. Upper esophageal sphincter (cricopharyngeus) relaxes → opens to receive bolus
  6. Pharyngeal peristaltic wave propels bolus into esophagus
  7. Respiration is inhibited (swallowing apnea)

Phase 3: Esophageal (Involuntary) Phase

• Duration: 8-20 seconds (liquids: ~1 sec; solids: ~5-8 sec)
• Control: Enteric nervous system + medullary swallowing center (via vagus)
• Events:
  1. Primary peristalsis - peristaltic wave initiated in pharynx travels down esophagus at 2-4 cm/sec propelling bolus; pressure wave ~30-120 mmHg
  2. Secondary peristalsis - if any food remains in esophagus (stretch activates it), additional peristaltic wave is generated (not initiated by voluntary swallowing)
  3. Lower Esophageal Sphincter (LES) relaxes (reflex, mediated by VIP and NO from enteric nervous system) as the peristaltic wave approaches → bolus enters stomach
  4. LES then contracts again to prevent acid reflux

Swallowing Center:

• Located in medulla oblongata (NTS + nucleus ambiguus)
• Coordinates all 26 muscles involved in swallowing
• Inputs from cranial nerves V, IX, X
• Outputs via CN V, VII, IX, X, XII + cervical nerves

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Q.5C - Tubuloglomerular Feedback (TGF) (5 marks)

Location: Juxtaglomerular Apparatus (JGA)

• Macula densa (specialized cells of thick ascending limb of loop of Henle, contiguous with DCT) - the sensor
• Juxtaglomerular (JG) cells (granular cells in wall of afferent arteriole) - produce renin
• Extraglomerular mesangial cells (Lacis cells) - mediators

Mechanism:

↑ GFR
    ↓
↑ NaCl delivery to macula densa (thick ascending limb)
    ↓
Macula densa senses ↑ NaCl via NKCC2 cotransporter
    ↓
Macula densa releases: adenosine, thromboxane A₂, ATP
    ↓
Afferent arteriole CONSTRICTION
    ↓
↓ GFR (returns toward normal) - NEGATIVE FEEDBACK LOOP

↓ GFR → ↓ NaCl at macula densa → ↑ renin release → ↑ Ang II → efferent arteriole constriction → ↑ GFR back to normal

Key Mediators:

• Adenosine - main mediator of afferent arteriole constriction in TGF
• ATP - released from macula densa cells, converted to adenosine by CD73
• Nitric oxide (NO) - antagonizes TGF (vasodilatory, released from macula densa with low NaCl)
• Prostaglandins (PGE₂) - modulate TGF
• Renin - released when NaCl is low → activates RAAS → ↑ Ang II → efferent constriction

Physiological Importance:

1. Autoregulation of GFR - keeps GFR constant (80-180 mmHg range of arterial pressure)
2. Prevents urinary salt wasting - if GFR suddenly rises, TGF brings it back down so tubules are not overwhelmed
3. Maintains glomerulotubular balance - coordinates GFR with tubular transport capacity
4. Links to RAAS - macula densa also controls renin secretion

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Q.5D - Role of Distal Convoluted Tubule (DCT) and Collecting Tubule in Urine Formation (5 marks)

Distal Convoluted Tubule (DCT)

• Early DCT (DCT1): major NaCl reabsorption
• Late DCT (DCT2): mineralocorticoid-sensitive, transitions into collecting duct

• NaCl reabsorption via apical NCC (Na⁺-Cl⁻ cotransporter) - site of action of thiazide diuretics
• Na⁺ exits basolateral side via Na⁺/K⁺ ATPase
• Impermeable to water (no AQP2) → dilution of tubular fluid
• Ca²⁺ reabsorption via apical TRPV5 channel → stimulated by PTH and 1,25-Vit D
• Mg²⁺ reabsorption via TRPM6

• Principal cells: Na⁺ reabsorption via ENaC (epithelial Na⁺ channel), K⁺ secretion - aldosterone upregulates ENaC and Na⁺/K⁺ ATPase
• Alpha-intercalated cells: H⁺ secretion (H⁺-ATPase) → acid-base regulation
• Beta-intercalated cells: HCO₃⁻ secretion (pendrin)

Collecting Duct (CD)

1. Na⁺ reabsorption via ENaC (aldosterone-stimulated) → drives K⁺ secretion
2. K⁺ secretion via ROMK channels - major site of K⁺ regulation
3. Water reabsorption via AQP2 - only when ADH (vasopressin) is present
   • ADH binds V2 receptors → ↑ cAMP → PKA → inserts AQP2 channels into apical membrane → water follows osmotic gradient into hypertonic medullary interstitium

• Secrete H⁺ into urine (H⁺-ATPase + H⁺/K⁺ ATPase)
• Reabsorb HCO₃⁻ via basolateral Cl⁻/HCO₃⁻ exchanger (AE1)
• Critical for acid-base homeostasis and final urine pH determination

• Secrete HCO₃⁻ (via pendrin) into urine when alkalotic
• Reabsorb H⁺ basally

• UT-A1 and UT-A3 urea transporters (upregulated by ADH)
• Urea contributes to medullary hyperosmolarity (~600 mOsm from urea in deep medulla)

Summary of DCT and CD Functions:

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Q.6 - Short Answer Questions (4×2 = 8 marks)

Q.6A - Caisson Disease (2 marks)

1. At high pressure (underwater diving), more nitrogen dissolves in blood and tissues (Henry's Law: solubility ∝ partial pressure)
2. On rapid ascent/decompression, nitrogen comes out of solution as gas bubbles (like opening a carbonated drink)
3. Bubbles form in:
   • Joints → pain ("the bends") - most common
   • Spinal cord → paraplegia
   • Brain → neurological deficits
   • Lungs → "chokes" (dyspnea, chest pain)
   • Skin → pruritus, marbling
   • Inner ear → vertigo, deafness

• Joint pain (knees, shoulders, hips) - "bends"
• Respiratory distress - "chokes"
• Neurological symptoms - "staggers"
• Skin mottling, pruritus

• Immediate recompression in a hyperbaric oxygen chamber
• Gradual decompression following established decompression tables
• 100% O₂ breathing helps wash out nitrogen

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Q.6B - Migratory Motor Complex (MMC) (2 marks)

• Motilin (from M cells of duodenum/jejunum) - primary hormonal trigger for Phase III
• Migrating myoelectric complex is also coordinated by the enteric nervous system and vagus
• Eating abolishes MMC → replaced by "fed pattern" (irregular contractions)

• "Housekeeper of the gut" - sweeps undigested residue, bacteria, and debris from stomach and small intestine to colon
• Prevents bacterial overgrowth in small intestine
• Moves indigestible particles (bones, seeds) that cannot be processed during eating

• Disrupted MMC → Small intestinal bacterial overgrowth (SIBO)
• Erythromycin (motilin agonist) → stimulates MMC → used as a prokinetic

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Q.6C - Effect of Moderate Exercise on Heart Rate and Blood Pressure (2 marks)

During Moderate Exercise:

• Increases significantly (from 70 to ~120-140 bpm in moderate exercise)
• Mechanism:
  • Central command (motor cortex) → inhibits vagal tone even before exercise starts (feedforward)
  • ↓ Parasympathetic tone (vagal withdrawal) - main mechanism early on
  • ↑ Sympathetic stimulation of SA node (↑ chronotropy)
  • Bainbridge reflex - ↑ venous return → ↑ HR
  • Circulating catecholamines (epinephrine) from adrenal medulla

• Exercising muscles: local vasodilation (↑ CO₂, ↑ K⁺, adenosine, NO, lactic acid, ↓ O₂, ↑ temperature)
• Splanchnic and renal vasoconstriction (sympathetic) → redirects blood to muscles
• ↑ Cardiac output = ↑ HR × ↑ Stroke Volume (Frank-Starling + ↑ contractility)
• Venous return ↑ (muscle pump, respiratory pump)

• BP and HR return to normal within minutes
• Well-trained athletes: faster recovery

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Q.6D - Heat Stroke (2 marks)

Types:

1. Classic (non-exertional) heat stroke - elderly, chronically ill during heat waves
2. Exertional heat stroke - young healthy athletes during intense exercise in hot/humid environment

Pathophysiology:

1. Overwhelming heat load (environmental + metabolic) exceeds heat loss capacity
2. Thermoregulatory failure - hypothalamus cannot maintain homeostasis; core temp rises rapidly
3. Sweating mechanism overwhelmed or fails (especially in classic heat stroke - anhidrosis)
4. High temperature causes:
   • Direct protein denaturation and cellular injury
   • Endothelial injury → systemic inflammatory response (like sepsis)
   • Rhabdomyolysis (muscle breakdown)
   • DIC (disseminated intravascular coagulation)
   • Acute kidney injury, hepatic failure, cardiac arrhythmias

Classic Features:

• Core temperature >40°C
• CNS dysfunction (confusion, seizure, coma) - distinguishes heat stroke from heat exhaustion
• Anhidrosis (dry, hot skin) in classic type; profuse sweating in exertional type
• Tachycardia, tachypnea, hypotension

Difference from Heat Exhaustion:

Treatment:

• Immediate cooling is the priority (ice water immersion most effective, or evaporative cooling)
• IV fluids, oxygen
• Monitor for organ failure (kidneys, liver, coagulation)
• No antipyretics (not effective - not mediated by prostaglandins)

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