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Rohilkhand Medical College — 2nd Terminal Exam April 2025 (Physiology)

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QUESTION 1 (13 Marks) — Jaundice Case Study

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1a. Type of Jaundice (1 Mark)

• Predominantly direct (conjugated) bilirubin elevated (16/20 mg% = 80% direct)
• Dark urine (conjugated bilirubin filtered by kidneys)
• Clay/pale stools (no bilirubin reaches gut → no stercobilinogen)
• Urobilinogen absent in urine (no gut-bacteria conversion of bilirubin → no urobilinogen reabsorption)
• ALP markedly elevated (bile duct obstruction)

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

• ALP 800 U/L (normal: 40–130 U/L) — markedly elevated
• In biliary obstruction, back-pressure induces synthesis and regurgitation of ALP from bile duct epithelium into blood
• ALP elevation >3× normal strongly suggests cholestasis or bile duct obstruction
• It is used to differentiate hepatocellular jaundice (moderate ALP rise) from obstructive jaundice (marked ALP rise)
• ALP isoforms can be checked: liver ALP helps distinguish from bone ALP

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1c. Difference Between Unconjugated & 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. Liver synthesizes primary bile acids (cholic acid, chenodeoxycholic acid) from cholesterol → conjugated with glycine or taurine → secreted as bile salts into bile
2. Gallbladder stores and concentrates bile between meals
3. On eating, CCK (cholecystokinin) triggers gallbladder contraction → bile released into duodenum
4. Bile salts emulsify fats and aid lipid digestion in small intestine
5. 95% of bile salts are actively reabsorbed in the terminal ileum via sodium-bile acid cotransporter
6. Absorbed bile salts enter the portal vein → return to liver
7. Liver re-extracts bile salts (first-pass extraction ~95%) and re-excretes them into bile
8. 5% bile salts reach colon → deconjugated by bacteria → secondary bile acids (deoxycholic, lithocholic) → partially reabsorbed passively

• Total bile salt pool = 3–5 g; circulates 6–10 times/day
• Allows a small pool to support large fat digestion requirements
• Disruption (ileal disease, cholestyramine) causes fat malabsorption and steatorrhoea
• Primary mechanism for cholesterol elimination from body

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QUESTION 2 (13 Marks) — Pituitary Hormones, Growth Hormone

Hormones of Anterior and Posterior Pituitary (3+3 = 6 marks for enumeration)

Anterior Pituitary (Adenohypophysis) — "FLAT PiG"

Posterior Pituitary (Neurohypophysis) — Hormones made in hypothalamus, stored here

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Regulation of Growth Hormone Secretion (3 Marks)

• GHRH (Growth Hormone-Releasing Hormone) from hypothalamus → binds to somatotrophs → stimulates GH secretion
• Ghrelin (from stomach) → stimulates GHRH and directly stimulates GH
• Hypoglycaemia, fasting, exercise, stress, sleep (deep sleep = peak GH)
• Alpha-adrenergic agonists, amino acids (arginine)
• Oestrogens, testosterone, thyroid hormones

• Somatostatin (GHIH) from hypothalamus → inhibits GH release
• IGF-1 (Insulin-like Growth Factor-1, made in liver) → negative feedback on both hypothalamus and pituitary
• GH itself → short-loop negative feedback
• Hyperglycaemia, free fatty acids, obesity

GHRH → Anterior Pituitary → GH → Liver → IGF-1 → ↓GHRH and ↑Somatostatin (negative feedback)

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Functions of Growth Hormone (7 Marks — discussed)

1. Skeletal growth — stimulates chondrocyte proliferation at epiphyseal growth plates → linear growth
2. Organ growth — increases size of liver, kidney, heart, skeletal muscles
3. Protein synthesis — promotes amino acid uptake and nitrogen retention (anabolic)

• Stimulates immune function (thymic growth)
• Promotes wound healing
• Increases milk production (synergistic with prolactin)

• Excess in childhood → Gigantism
• Excess in adulthood → Acromegaly (enlarged jaw, hands, feet, tongue)
• Deficiency in childhood → Pituitary dwarfism (proportionate short stature)

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QUESTION 3 (14 Marks) — Cardiac Cycle

Definition (1 Mark)

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Phases of Cardiac Cycle (10 Marks) — with Pressure-Volume Changes

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DIASTOLE

• Mitral & tricuspid valves open (AV valves open)
• Aortic & pulmonary valves closed
• Blood rushes from atria → ventricles (passive flow)
• LV volume rises rapidly (from ~50 mL to ~110 mL)
• LV pressure remains low (~5–10 mmHg)
• Produces the 3rd Heart Sound (S3) in children (normal) or pathological in adults

• Continued slow passive filling
• AV valves still open
• LV pressure and volume rise slowly

• Atrial contraction → adds ~20–30% extra blood to ventricles
• End-Diastolic Volume (EDV) = 120–130 mL
• Produces the 4th Heart Sound (S4) — atrial gallop (abnormal)
• P wave on ECG

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SYSTOLE

• QRS complex on ECG — ventricles begin contracting
• AV valves close (mitral + tricuspid close) → 1st Heart Sound (S1) "Lub"
• Aortic and pulmonary valves still closed
• Volume constant (no blood ejected yet), pressure rises rapidly
• LV pressure rises from ~8 mmHg → ~80 mmHg
• Duration: ~0.05 s

• LV pressure exceeds aortic pressure (~80 mmHg) → Aortic valve opens
• Blood ejected rapidly into aorta
• LV volume falls from 130 mL → ~70 mL
• LV pressure rises to peak systolic pressure (~120 mmHg)
• T wave on ECG begins

• Slower ejection of remaining blood
• LV pressure begins to fall
• Volume decreases to End-Systolic Volume (ESV) = 50–60 mL
• Stroke volume = EDV − ESV = ~70 mL

• Ventricles relax; pressure falls below aortic pressure
• Aortic & pulmonary valves close → 2nd Heart Sound (S2) "Dub"
• AV valves still closed
• Volume constant, pressure falls rapidly
• Duration: ~0.08 s
• Dicrotic notch on aortic pressure curve (closure of aortic valve)

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Pressure-Volume Changes Summary

           Isovolumetric       Ejection         Isovolumetric
           Contraction     (Rapid → Slow)       Relaxation
              ↑LV P              ↑LV P              ↓LV P
              Volume      Volume ↓ (stroke vol)   Volume
              constant    ESV = 50-60mL           constant

 AV valves: Open → CLOSE ──────────────────────── closed → Open
 Ao valves: Closed ──────── OPEN ──────────────── CLOSE ───────

• EDV = 120–130 mL
• ESV = 50–60 mL
• Stroke Volume = 70 mL
• Ejection Fraction = SV/EDV = 70/130 ≈ 55%
• Peak LV systolic pressure = ~120 mmHg
• LV diastolic pressure = ~8 mmHg

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Difference Between First and Second Heart Sound (3 Marks)

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

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4a. GFR & Factors Affecting It (5 Marks)

• Normal GFR = 125 mL/min (180 L/day) in adults
• Measured by inulin clearance or estimated by creatinine clearance

• P_GC = Glomerular capillary hydrostatic pressure (~60 mmHg) → favours filtration
• P_BS = Bowman's space hydrostatic pressure (~18 mmHg) → opposes filtration
• π_GC = Glomerular capillary oncotic pressure (~32 mmHg) → opposes filtration
• π_BS = Bowman's space oncotic pressure (~0) → negligible
• Net filtration pressure ≈ 10 mmHg
• Kf = Filtration coefficient (permeability × surface area)

1. ↑ Renal blood flow / renal plasma flow
2. ↑ Glomerular capillary pressure (efferent arteriole constriction)
3. ↑ Kf (increased permeability)
4. Dilation of afferent arteriole (prostaglandins, ANP)
5. Low plasma protein (↓ oncotic pressure)

1. ↓ Renal blood flow (hemorrhage, heart failure, dehydration)
2. Afferent arteriolar constriction (sympathetic stimulation, angiotensin II)
3. ↑ Bowman's space pressure (ureteral obstruction)
4. ↑ Plasma oncotic pressure (hyperproteinaemia)
5. Glomerulonephritis (↓ Kf)
6. Angiotensin II → dilates efferent arteriole (via AT1) → ↓ GFR (at high levels)

• GFR is autoregulated between MAP 80–180 mmHg
• Myogenic mechanism + Tubuloglomerular feedback (macula densa senses NaCl → controls afferent arteriole tone)

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4b. Caisson's Disease (5 Marks)

• Occurs in deep-sea divers, tunnel workers (caisson workers), aviators
• At high pressure, more nitrogen dissolves in blood and tissues (Henry's Law: amount of gas dissolved ∝ partial pressure)
• On rapid ascent/decompression, nitrogen comes out of solution as bubbles before lungs can eliminate it

1. Bubbles in joints → joint pain (bends)
2. Bubbles in spinal cord → paraplegia
3. Bubbles in coronary vessels → MI
4. Bubbles in lungs → pulmonary embolism ("chokes")
5. Aseptic bone necrosis (dysbaric osteonecrosis) — long-term complication

• Recompression in hyperbaric oxygen chamber (100% O₂ at 2.8 ATA)
• Gradual, staged decompression
• Fluids + rest

• Slow, staged decompression stops
• Follow decompression tables (e.g., US Navy tables)
• Pre-dive fitness assessment

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4c. Wallerian Degeneration (5 Marks)

• Axon distal to injury becomes separated from cell body
• Loss of axonal transport → structural breakdown begins
• Schwann cells begin to respond

• Axoplasm becomes granular and fragmented
• Neurofilaments and microtubules disintegrate
• Axon swells then breaks into fragments

• Myelin sheath breaks down into ovoid segments
• Myelin debris accumulates

• Macrophages invade and phagocytose axon and myelin debris
• Schwann cells proliferate and form "bands of Büngner" — longitudinal tubular structures that guide regenerating axons

• Chromatolysis (dissolution of Nissl substance) in cell body = axon reaction
• Cell body attempts regeneration
• Sprouts grow at ~1–4 mm/day along Schwann cell tubes

• Loss of nerve conduction distal to lesion
• Denervation of target muscle → denervation atrophy + fibrillation potentials on EMG
• If pathway intact → regeneration possible at 1 mm/day

• EMG shows fibrillation 2–3 weeks after injury
• Nerve conduction studies show absent response distal to injury
• Recovery depends on distance to re-innervation target

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4d. Facilitated Diffusion (5 Marks)

1. Passive — moves down concentration gradient (high → low)
2. No energy (ATP) required
3. Carrier-mediated — requires specific membrane proteins
4. Exhibits specificity (each transporter is specific to a substrate)
5. Exhibits saturation kinetics (Michaelis-Menten) — rate plateaus at Vmax
6. Competitive inhibition possible (structurally similar molecules compete)
7. Not inhibited by metabolic poisons (unlike active transport)

• Channel proteins — aquaporins (water), ion channels (Na⁺, K⁺, Cl⁻, Ca²⁺)
• Carrier/transporter proteins (uniporters) — GLUT transporters

• GLUT transporters have conformational change
• Glucose binds → conformational shift → released on other side
• Rate depends on concentration gradient and number of available carriers

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4e. Oral Contraceptive Pills (OCP) (5 Marks)

• Contains oestrogen + progestogen (synthetic)
• Most common: Ethinyl estradiol + levonorgestrel/norethisterone/desogestrel

• Contains progestogen only
• Used in lactating women, contraindication to oestrogen

• Reduces dysmenorrhoea and menorrhagia
• Treats PCOS, endometriosis, acne
• Reduces risk of ovarian and endometrial cancer
• Regulates menstrual cycle

• Nausea, breast tenderness, headache, mood changes
• Thromboembolism (DVT, PE) — due to oestrogen effect on clotting factors (↑ Factors II, VII, X, fibrinogen)
• Hypertension, fluid retention
• Risk of stroke in migraine with aura
• Reduced libido

• History of DVT/PE/stroke
• Smokers >35 years
• Breast cancer
• Migraine with aura
• Uncontrolled hypertension
• Liver disease

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4f. Mechanism of Innate Immunity (5 Marks)

• Skin (mechanical barrier)
• Mucous membranes, cilia (mucociliary clearance)
• Lysozyme in tears/saliva
• Gastric acid (pH 2)
• Normal flora (competitive exclusion)

• Recognise PAMPs (Pathogen-Associated Molecular Patterns) — conserved microbial structures
• Examples: LPS, peptidoglycan, flagellin, dsRNA, CpG DNA
• Receptors: Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I
• Activation → NF-κB pathway → pro-inflammatory cytokines

• Alternative pathway (spontaneous) and Lectin pathway activated without antibodies
• Opsonisation (C3b), chemotaxis (C5a), MAC (C5b–C9) → cell lysis

• IL-1, IL-6, TNF-α → fever, acute phase proteins
• Type I Interferons (IFN-α, IFN-β) → antiviral defense
• IL-12 → activates NK cells and T helper cells

• Liver produces CRP, mannose-binding lectin, fibrinogen
• CRP binds phospholipids on bacteria → activates complement + opsonisation

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4g. Renin-Angiotensin-Aldosterone Axis (RAAS) (5 Marks)

1. ↓ Renal perfusion pressure (detected by JGA — juxtaglomerular apparatus)
2. ↓ NaCl delivery to macula densa
3. ↑ Sympathetic activity (β₁-receptor stimulation of JG cells)
4. Haemorrhage, dehydration, sodium depletion

STIMULUS (↓BP, ↓Na⁺, ↑Sympathetic)
        ↓
Juxtaglomerular cells → Release RENIN
        ↓
Angiotensinogen (liver) → ANGIOTENSIN I (10 aa)
        ↓ ACE (Angiotensin Converting Enzyme) — lung
ANGIOTENSIN II (8 aa)
        ↓
┌─────────────────────┬──────────────────────┐
│ Adrenal Cortex       │ Blood Vessels         │ Kidney/Brain
│ → Aldosterone        │ → Vasoconstriction    │ → ↑ADH, thirst
│ (zona glomerulosa)   │ → ↑TPR → ↑BP         │ → ↓GFR
└─────────────────────┴──────────────────────┘
        ↓ Aldosterone
Kidney collecting duct:
→ ↑Na⁺ reabsorption (via ENaC + Na⁺/K⁺-ATPase)
→ ↑K⁺ and H⁺ excretion
→ ↑Water retention → ↑Blood volume → ↑BP

1. Potent vasoconstriction (↑ TPR → ↑BP)
2. Stimulates aldosterone release
3. Stimulates ADH release
4. Stimulates thirst center (hypothalamus)
5. Promotes efferent arteriole constriction (maintains GFR)
6. Cardiac and vascular remodeling (hypertrophy)

• Acts on principal cells of collecting duct
• ↑ Na⁺ channel (ENaC) expression
• ↑ Na⁺/K⁺-ATPase activity on basolateral side
• Net: Na⁺ and water retained; K⁺ excreted

• ↑ BP → ↓ renin release
• ↑ Na⁺ → ↓ renin release
• ANP (atrial natriuretic peptide) inhibits renin + aldosterone

• ACE inhibitors (enalapril) and ARBs (losartan) → treatment of hypertension, heart failure, diabetic nephropathy
• Primary hyperaldosteronism (Conn's syndrome) → hypertension + hypokalaemia
• Secondary hyperaldosteronism → renovascular hypertension

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4h. Movements of Small Intestine (5 Marks)

• Most common movement of small intestine
• Non-propulsive; produced by circular muscle contractions
• Ring-like contractions that divide intestinal contents into segments
• Adjacent segments relax while contracted ones relax → "kneading" effect
• Purpose: Mix chyme with digestive enzymes and bile; increase contact with mucosal surface for absorption
• Rate: Duodenum = 12/min; Ileum = 8–9/min (set by pacemaker cells/ICCs)
• Controlled by intrinsic pacemaker cells (ICCs) and enteric nervous system

• Progressive wave of contraction moving aborally (oral → anal direction)
• Mechanism: Law of intestine (Bayliss & Starling) — distension → contraction above (ascending excitation) and relaxation below (descending inhibition)
• Propels chyme toward colon
• Slow in small intestine — allows adequate absorption time
• Mediated by: 5-HT (serotonin) released by enterochromaffin cells → activates enteric neurons

• Very rapid, strong peristalsis traversing the entire small intestine
• Occurs in severe irritation (e.g., cholera, severe gastroenteritis)
• Rapidly clears intestinal contents → diarrhoea

• Occurs during fasting/interdigestive period (when no food present)
• Originates in stomach → migrates to ileum every 90–120 minutes
• Clears the bowel of remaining debris, bacteria, undigested material
• 4 Phases: Phase I (quiescence) → Phase II (irregular contractions) → Phase III (intense regular contractions — "activity front") → Phase IV (transition)
• Regulated by motilin (hormone from duodenum/jejunum)
• Absent after eating (replaced by fed-pattern segmentation)

• Villi contract rhythmically (shortening and lengthening)
• Muscularis mucosae contractions
• Enhances lymph flow through lacteals
• Improves contact between villus surface and chyme

• Gastroileal reflex: eating → gastric distension → relaxation of ileocaecal valve → chyme passes to colon
• Cecum distension → sphincter contracts (prevents backflow)

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Reference Sources: Guyton & Hall Textbook of Medical Physiology (14th Ed); Costanzo Physiology (7th Ed); Ganong's Review of Medical Physiology (26th Ed); Medical Physiology — Boron & Boulpaep; Bradley & Daroff's Neurology in Clinical Practice; Sleisenger & Fordtran's Gastrointestinal and Liver Disease