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Rohilkhand Medical College — Physiology 2nd Terminal Exam

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QUESTION 1 — Jaundice (1+1+3+6+2 = 13 marks)

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1a. Type of Jaundice in this Case (1 mark)

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1b. Clinical Significance of Serum Alkaline Phosphatase (ALP) (1 mark)

• ALP > 3× upper limit of normal = strong indicator of cholestasis (intra- or extra-hepatic biliary obstruction)
• In this case, ALP = 800 U/L (markedly elevated), confirming biliary obstruction
• ALP rises because obstruction causes regurgitation of bile back into liver sinusoids, increasing hepatic ALP synthesis and release
• It helps differentiate obstructive jaundice (ALP ↑↑↑) from hepatocellular jaundice (ALT/AST ↑↑↑ more prominent)
• Also elevated in bone disease, Paget's disease, pregnancy (placental ALP)

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1c. Tabulate Difference Between Unconjugated and Conjugated Bilirubin (3 marks)

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1d. Difference Between Hemolytic, Hepatic & Obstructive Jaundice (6 marks)

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1e. Enterohepatic Circulation (2 marks)

1. Hepatic synthesis: Primary bile acids (cholic acid and chenodeoxycholic acid) are synthesized from cholesterol in hepatocytes and conjugated with glycine or taurine → conjugated bile salts
2. Secretion: Secreted into bile → stored in gallbladder → released into duodenum on eating
3. Intestinal action: Emulsify fats, facilitate absorption of fat-soluble vitamins (A, D, E, K)
4. Reabsorption: Conjugated bile salts are actively absorbed in the terminal ileum (via IBAT/ASBT transporters); some passive absorption of unconjugated forms throughout the gut
5. Portal return: Reabsorbed bile salts enter portal blood → taken up by hepatocytes → reconjugated → re-secreted into bile
6. Fecal loss: Only 5% escapes → excreted in feces as secondary bile acids (deoxycholic acid, lithocholic acid formed by bacterial deconjugation)

• Pool size: 2–4 g; circulates 5–10 times/day
• ~95% efficient; fecal loss = 0.2–0.4 g/day (compensated by hepatic synthesis)
• Rate-limiting enzyme: CYP7A1 (cholesterol 7α-hydroxylase)
• Regulated by FXR (Farnesoid X Receptor) and FGF19 (ileum-derived, suppresses CYP7A1)

• Maintains fat digestion and vitamin absorption
• Important in cholesterol homeostasis
• Disruption (ileal disease, bile acid sequestrants) → malabsorption and diarrhea

— Guyton and Hall Textbook of Medical Physiology; Harrison's Principles of Internal Medicine 22E

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QUESTION 2 — Pituitary Hormones, Growth Hormone Regulation & Functions (3+3+7 = 13 marks)

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2a. Hormones of Anterior and Posterior Pituitary Gland (3 marks)

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2b. Regulation of Growth Hormone (3 marks)

• GHRH (Growth Hormone Releasing Hormone) → stimulates GH release (pulsatile pattern)
• Somatostatin (GHIH) → inhibits GH release (from hypothalamus and other tissues)

• Deep sleep (slow-wave sleep, stage 3–4) — largest daily pulse
• Exercise and physical stress
• Hypoglycemia (falling blood glucose)
• Fasting and protein deficiency
• Amino acids (especially arginine, leucine)
• Estrogens, testosterone
• Dopamine, α-adrenergic agonists
• Ghrelin (from stomach) — potent GH secretagogue acting on GHSR

• Hyperglycemia (glucose load)
• Elevated free fatty acids
• Cortisol/glucocorticoids (chronic excess)
• IGF-1 and GH itself (negative feedback — short-loop and long-loop feedback)
• Somatostatin
• Obesity

• Short-loop feedback: GH inhibits its own release from pituitary
• Long-loop feedback: IGF-1 (produced by liver in response to GH) inhibits both GHRH release from hypothalamus and GH release from pituitary

Hypothalamus
  ↓ GHRH (+) / Somatostatin (−)
Anterior Pituitary
  ↓ GH
Liver → IGF-1
  ↓ Target tissues (bone, muscle, fat)
  ↑ IGF-1 feeds back to inhibit GH and GHRH

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2c. Functions of Growth Hormone (7 marks)

1. Skeletal/Linear Growth:
   • Stimulates proliferation of chondrocytes at the epiphyseal growth plate
   • Acts via IGF-1 → increases bone length (before epiphyseal fusion)
   • Increases bone density and periosteal bone formation
2. Protein Synthesis:
   • Increases amino acid uptake into cells
   • Stimulates ribosomal RNA transcription → positive nitrogen balance
   • Promotes muscle hypertrophy
3. Organ Growth:
   • Increases size of most visceral organs (liver, kidneys, heart, spleen — except brain and eyes)

1. Carbohydrate Metabolism (diabetogenic):
   • Decreases insulin sensitivity (insulin resistance) at muscle and adipose tissue
   • Increases hepatic gluconeogenesis
   • Net effect: raises blood glucose ("anti-insulin" or "diabetogenic" effect)
2. Fat Metabolism (lipolytic):
   • Stimulates lipolysis in adipose tissue → releases FFA into blood
   • Increases fat oxidation for energy (protein-sparing effect)
   • Decreases fat stores (body fat)
3. Mineral/Electrolyte Metabolism:
   • Promotes Ca²⁺ absorption from intestine and reduces renal Ca²⁺ excretion
   • Causes positive balance of Na⁺, K⁺, Cl⁻, and phosphate
   • Increases extracellular fluid volume

1. Immune function: Enhances T-lymphocyte proliferation; immunostimulatory
2. Cardiovascular: Increases cardiac output (at physiological levels)
3. GH in Deficiency: Short stature, delayed puberty, increased adiposity, reduced muscle mass
4. GH in Excess:
   • Before epiphyseal closure → Gigantism
   • After epiphyseal closure → Acromegaly (enlargement of hands, feet, jaw, visceral organs)

— Guyton and Hall Textbook of Medical Physiology; Ganong's Review of Medical Physiology

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QUESTION 3 — Cardiac Cycle (1+10+3 = 14 marks)

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3a. Definition of Cardiac Cycle (1 mark)

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3b. Phases of Cardiac Cycle with Pressure-Volume Changes and Events (10 marks)

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• Duration: ~0.5 sec
• Events: AV valves (mitral, tricuspid) open; semilunar valves closed
• Sub-phases:
  • Rapid filling: Ventricles relax → pressure drops below atrial pressure → AV valves open → 70–80% of ventricular filling occurs
  • Diastasis (slow filling): Gradual rise in ventricular volume
  • Atrial kick: Atrial contraction (P wave on ECG) → adds remaining 20–30% of filling (up to 40% during exercise)
• Pressure: LV pressure ~0–8 mmHg; LA pressure slightly higher (~6–8 mmHg)
• Volume: LV volume rises from ~50 mL (ESV) to ~120–130 mL (EDV = End-Diastolic Volume)
• ECG: P wave → atrial depolarization at end of this phase

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• Duration: ~0.05 sec
• Events: Ventricles begin to contract (QRS complex) → LV pressure rises rapidly → exceeds LA pressure → mitral valve closes (S1 — First Heart Sound); aortic valve still closed
• Both AV and semilunar valves are CLOSED
• Pressure: LV pressure rises steeply from 8 mmHg toward 80 mmHg
• Volume: Remains constant (no ejection) = isovolumetric
• ECG: QRS complex

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• Duration: ~0.3 sec
• Events: LV pressure exceeds aortic pressure (~80 mmHg) → aortic valve opens
• Sub-phases:
  • Rapid ejection: LV pressure continues to rise to ~120 mmHg (systolic); aortic pressure closely follows; ventricular volume falls rapidly; ~70 mL ejected
  • Reduced ejection: LV pressure begins to fall, aortic pressure also falls; ventricular volume continues to decrease but slower
• Ejection Fraction (EF): = Stroke Volume (70 mL) / EDV (120–130 mL) ≈ 60–70%
• End-Systolic Volume (ESV): ~50–60 mL remains in ventricle
• ECG: ST segment and T wave

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• Duration: ~0.08 sec
• Events: Ventricular pressure falls below aortic pressure → backflow of blood → aortic valve closes (S2 — Second Heart Sound); AV valves still closed; dicrotic notch on aortic pressure trace
• Both valves CLOSED again
• Pressure: LV pressure falls rapidly from ~80 mmHg to ~0 mmHg
• Volume: Constant (no inflow or outflow) = isovolumetric
• ECG: T wave (end) / isoelectric line

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Volume (mL)
 120|.....B
    |     |\ 
    |     | \  Ejection (C→D)
    |     |  \
  50|     |   D
    |     |   |
    |  A..|...|  
    |  Isovol  |
    0___________
      0    120 Pressure (mmHg)

A = Mitral opens (filling begins)
B = Mitral closes / Isovol. contraction starts
C = Aortic opens / Ejection begins
D = Aortic closes / Isovol. relaxation starts

• Aortic pressure: 120 mmHg (systolic) / 80 mmHg (diastolic)
• Pulse pressure: 120 − 80 = 40 mmHg
• Stroke volume: ~70 mL (at rest)
• Cardiac output: 70 mL × 75/min ≈ 5 L/min
• JVP waves: 'a' (atrial contraction), 'c' (tricuspid closure), 'x' descent, 'v' (venous filling), 'y' descent (tricuspid opens)

— Medical Physiology (Boron & Boulpaep); Guyton and Hall Textbook of Medical Physiology

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3c. Differences Between First and Second Heart Sound (3 marks)

— Guyton and Hall Textbook of Medical Physiology

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QUESTION 4 — Short Notes (5 × 8 = 40 marks)

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4a. GFR and Factors Affecting It (5 marks)

• PGC = Glomerular capillary hydrostatic pressure = 60 mmHg (favors filtration)
• PBC = Bowman's capsule hydrostatic pressure = 18 mmHg (opposes filtration)
• πGC = Glomerular capillary oncotic pressure = 32 mmHg (opposes filtration)
• πBC = Bowman's capsule oncotic pressure ≈ 0 (favors filtration)

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• ↓ Kf: Chronic hypertension (thickened membrane), glomerulonephritis, diabetes → ↓ GFR
• ↑ Kf: Not a major normal regulator

• ↑ Afferent arteriole dilation → ↑ PGC → ↑ GFR
• ↑ Efferent arteriole constriction → ↑ PGC → ↑ GFR (e.g., angiotensin II)
• ↑ Systemic blood pressure → ↑ PGC → ↑ GFR (autoregulation counteracts this)

• Myogenic mechanism: ↑ BP → afferent arteriole constricts → keeps GFR constant
• Tubuloglomerular feedback: ↑ NaCl delivery to macula densa → adenosine release → afferent arteriole constriction → ↓ GFR
• Operates between MAP 75–160 mmHg

• ↑ RPF → washes out oncotic pressure gradient → ↑ GFR
• ↓ RPF (shock, dehydration) → ↓ GFR

• ↓ Plasma proteins (nephrotic syndrome, malnutrition) → ↓ πGC → ↑ GFR
• ↑ Plasma proteins (dehydration) → ↑ πGC → ↓ GFR

• ↑ Urinary obstruction → ↑ PBC → ↓ GFR
• Ureteric stone, prostatic hypertrophy → obstructive nephropathy

• Norepinephrine/Angiotensin II: Preferentially constrict efferent > afferent → initially maintain GFR but in severe states ↓ GFR
• Prostaglandins (PGE2, PGI2): Dilate afferent arteriole → maintain GFR during stress
• ANP (Atrial Natriuretic Peptide): Dilates afferent, constricts efferent → ↑ GFR
• NSAIDs: Block prostaglandins → constrict afferent → ↓ GFR (especially in volume-depleted states)

— Guyton and Hall Textbook of Medical Physiology

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4b. Caisson's Disease (5 marks)

• Named after workers ("caissons") who built underwater structures and suffered symptoms on rapid ascent
• At high pressures (deep sea diving, compressed air tunnels), nitrogen dissolves in body fluids and tissues (Henry's Law: gas dissolved ∝ partial pressure)
• On rapid ascent, pressure falls rapidly → nitrogen comes out of solution as bubbles (like carbonation in a soda bottle)

• Slow, staged ascent (decompression stops)
• Saturation diving protocols
• Pre-dive planning (dive tables, dive computers)

• Hyperbaric oxygen therapy (HBO): Recompress in hyperbaric chamber → nitrogen reabsorbs → gradual controlled decompression
• High-flow 100% O₂ (reduces bubble size)
• IV fluids, analgesia

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4c. Wallerian Degeneration (5 marks)

1. Hours 0–12: Axonal continuity disrupted → retrograde and anterograde transport fails; Ca²⁺ influx activates calpain proteases
2. Day 1–3: Axon begins to swell, become irregular, and fragment ("axon balling"); myelin sheath breaks down
3. Day 3–7: Schwann cells retract from nodes of Ranvier; activated Schwann cells and macrophages phagocytose myelin debris (clearing debris takes weeks); Schwann cells transform from myelin-producing cells to "repair cells" (upregulation of c-Jun)
4. Week 1–3: Entire axon undergoes Wallerian degeneration; Schwann cell tubes (bands of Büngner) form — these serve as conduits for regeneration

• Axon breaks down proximally up to the nearest node of Ranvier
• Cell body undergoes chromatolysis:
  • Dispersal of Nissl substance (rough ER)
  • Eccentric displacement of nucleus
  • Cell body swells
  • ↑ RNA synthesis → shift to regenerative protein synthesis

• Regenerating axon sprouts grow through the Schwann cell tubes (bands of Büngner) at ~1–4 mm/day
• Success depends on continuity of endoneurial tubes
• Collateral sprouting from intact adjacent axons also contributes to reinnervation

• Electrodiagnostic changes: Loss of compound motor action potential (CMAP) distally after 7–10 days
• EMG shows fibrillations and positive sharp waves 2–3 weeks after denervation
• Recovery possible if injury < 3–4 months (critical time before muscle fibrosis)

— Bradley and Daroff's Neurology in Clinical Practice

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4d. Facilitated Diffusion (5 marks)

1. Passive: Moves solutes from high → low concentration (downhill gradient)
2. No energy required (distinguishes it from active transport)
3. Carrier-mediated: Requires specific integral membrane proteins:
   • Channel proteins (ion channels, aquaporins — pore-like)
   • Carrier proteins (transporters — undergo conformational change)
4. Specificity: Each carrier/channel is specific for a particular molecule or ion
5. Saturation kinetics: Rate increases with concentration but reaches a maximum (Vmax) when all carriers are occupied — shows Michaelis-Menten kinetics
6. Competitively inhibited by structurally similar molecules

• GLUT4 deficiency/insensitivity → diabetes mellitus (insulin resistance)
• Aquaporin defects → nephrogenic diabetes insipidus

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4e. Oral Contraceptive Pills (OCPs) (5 marks)

• Contain estrogen (ethinyl estradiol) + progestin (various: levonorgestrel, norethindrone, desogestrel, drospirenone)
• Monophasic: fixed dose throughout 21-day cycle
• Biphasic/Triphasic: varying doses to mimic natural cycle

• Contains progestin only (e.g., norethindrone)
• Used in breastfeeding women, those who cannot take estrogen

• Reduces risk of ovarian and endometrial cancer
• Treats dysmenorrhea, endometriosis, PCOS, acne
• Reduces iron-deficiency anemia (lighter periods)
• Treats premenstrual syndrome

• Pregnancy; smokers >35 years; history of DVT/PE; breast cancer; active liver disease; migraine with aura; uncontrolled hypertension

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4f. Mechanism of Innate Immunity (5 marks)

• Skin: Mechanical barrier; low pH; antimicrobial peptides (defensins, cathelicidins)
• Mucus membranes: Ciliary action (mucociliary escalator); lysozyme in saliva and tears; stomach acid (pH 2)
• Normal flora: Competitive exclusion of pathogens

• Toll-like receptors (TLRs): TLR4 recognizes LPS (gram-negative bacteria); TLR3 → dsRNA (viruses)
• NOD-like receptors (NLRs): Intracellular bacteria; inflammasome (NLRP3) → IL-1β, IL-18
• RIG-I: Cytosolic RNA sensing
• Lectins (CLRs): Mannose receptor, Dectin-1

1. Pathogen breaches barrier → PAMPs recognized by TLRs on macrophages/dendritic cells
2. NF-κB activation → cytokine production (TNF-α, IL-1, IL-6, IL-12)
3. Complement activation → opsonization and MAC
4. Neutrophil recruitment → phagocytosis, oxidative killing
5. Inflammation: vasodilation, ↑ permeability, heat, swelling, redness
6. Dendritic cells present antigens → activate adaptive (T and B cell) immunity

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4g. Renin-Angiotensin-Aldosterone System (RAAS) (5 marks)

↓ Renal perfusion pressure / ↓ NaCl at macula densa / Sympathetic activation (β1)
          ↓
    RENIN released from
    Juxtaglomerular cells (JG cells)
          ↓
  Angiotensinogen (made in liver)
          ↓ [Renin]
  Angiotensin I (10 amino acids, inactive)
          ↓ [ACE — Angiotensin-Converting Enzyme — in lung]
  Angiotensin II (8 amino acids, ACTIVE)
          ↓
  Acts on AT1 receptors

1. ↓ Renal perfusion pressure (afferent arteriolar stretch receptors)
2. ↓ NaCl delivery to macula densa
3. Sympathetic stimulation (β₁ receptors on JG cells)
4. Prostaglandins (PGE2, PGI2) — enhance renin secretion

• Acts on principal cells of collecting duct
• ↑ Apical Na⁺ channels (ENaC) and basolateral Na⁺/K⁺-ATPase
• → Na⁺ retention + water retention + K⁺/H⁺ excretion
• Net effect: ↑ blood volume, ↑ BP

• ↑ Blood pressure → ↓ renin release (stretch receptors)
• ↑ Na⁺ at macula densa → ↓ renin (tubuloglomerular feedback)
• Angiotensin II itself → inhibits renin release (short-loop feedback)

— Brenner and Rector's The Kidney; Guyton and Hall Textbook of Medical Physiology

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4h. Movements of Small Intestine (5 marks)

• Most characteristic movement of the small intestine
• Distension of intestinal wall by chyme stimulates local contraction of circular muscle
• Produces ring-like constrictions at intervals along the intestine → divides it into segments (like a sausage chain)
• One set of contractions relaxes → new contractions occur between previous constrictions → effectively "chops" chyme 2–3 times/minute
• Frequency: 12/min in duodenum and proximal jejunum; 8–9/min in terminal ileum
• Controlled by slow-wave electrical activity (basic electrical rhythm, BER) + myenteric plexus excitation
• Blocked by atropine (antimuscarinic)
• Function: thorough mixing of chyme with pancreatic enzymes and bile; increases contact with absorptive mucosa

• Peristaltic waves propel chyme toward the ileocecal valve
• Initiated by distension → ascending excitation (contraction behind bolus) + descending inhibition (relaxation ahead of bolus) — Law of the Intestine (Starling's Law)
• Velocity: 0.5–2 cm/sec (faster proximally, slower distally)
• Waves are normally weak and travel only 3–5 cm before dying out
• Net movement of chyme: only ~1 cm/min → transit from pylorus to ileocecal valve takes 3–5 hours
• Enhanced by: Gastroenteric reflex (stomach distension → increased intestinal peristalsis), gastrin, CCK, insulin, motilin, serotonin
• Inhibited by: Secretin, glucagon, GLP-1, sympathetic stimulation

• Occurs during fasting (interdigestive state)
• Powerful cyclic contractions sweeping from stomach to terminal ileum
• Cycles every 90 minutes; driven by motilin (from duodenal mucosa)
• Phase I (quiescence) → Phase II (irregular contractions) → Phase III (intense bursts — the "housekeeper")
• Function: clears residual food, bacteria, and debris; prevents bacterial overgrowth in small intestine
• Abolished by feeding

• Villi contract and relax rhythmically under control of villikinin (hormone from intestinal mucosa)
• Enhances lymph flow in lacteals (important for fat absorption)

• Acts as a sphincter; prevents backflow from cecum into ileum
• Relaxes with each gastroileal reflex (following gastric filling → more chyme propelled into colon)

— Guyton and Hall Textbook of Medical Physiology

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