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SECTION B - Short Answer Questions

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ANATOMY [2 marks]

Q1. Draw a well-labeled diagram of skeletal muscle

MUSCLE (whole organ)
│
├── Epimysium - dense CT sheath surrounding entire muscle
│
├── Fascicle (bundle of fibers)
│   └── Perimysium - surrounds each fascicle
│
└── Muscle Fiber (single cell)
    └── Endomysium - surrounds each fiber
        │
        └── MYOFIBRIL
            │
            ├── I-band (light) - actin only
            ├── A-band (dark) - actin + myosin overlap
            ├── H-zone - myosin only
            ├── Z-line - anchors actin, defines sarcomere
            └── M-line - center of H-zone

Epimysium
 ┌──────────────────────────────┐
 │  Perimysium                  │
 │  ┌─────────────┐             │
 │  │ Fascicle    │  ← Fascicle │
 │  │ ┌──────┐   │             │
 │  │ │Fiber │   │  ← Muscle   │
 │  │ │  ↑   │   │    Fiber    │
 │  │ │ Endo │   │             │
 │  │ │ mysm │   │             │
 │  │ └──────┘   │             │
 │  └─────────────┘             │
 └──────────────────────────────┘

Sarcomere (one unit):
Z────I────A────H────A────I────Z
     actin  myosin  actin

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BIOCHEMISTRY [6 marks]

Q2. Synthesis and Importance of Melanin

Phenylalanine
     ↓ (Phenylalanine hydroxylase)
L-Tyrosine
     ↓ (Tyrosinase - rate-limiting, copper-dependent)
DOPA (3,4-dihydroxyphenylalanine)
     ↓ (Tyrosinase)
Dopaquinone
     ↓
     ├──→ Eumelanin (brown/black) - via cyclization & polymerization
     └──→ Pheomelanin (red/yellow) - via cysteine addition

• Eumelanin - brown/black pigment; predominant in darker skin
• Pheomelanin - red/yellow pigment; predominant in fair/red-haired individuals

1. Photoprotection - absorbs and scatters UV radiation, protecting DNA from UV-induced mutations
2. Skin color - determines racial/ethnic skin pigmentation
3. Antioxidant - scavenges free radicals
4. Eye protection - in choroid and retinal pigment epithelium, reduces light scatter
5. Neurological role - neuromelanin in dopaminergic neurons of substantia nigra (its loss is seen in Parkinson's disease)

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Q3. Biochemical Basis of Organophosphate Poisoning

Acetylcholine (ACh) → AChE → Choline + Acetate (inactivation)

Organophosphate + AChE → Phosphorylated AChE (irreversible inhibition)
                            ↓
            ACh accumulates at synapses

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Q4. Define and Classify Carbohydrates with Examples

• Based on carbon number: Trioses (C₃), Tetroses (C₄), Pentoses (C₅), Hexoses (C₆)
• Based on carbonyl group: Aldoses (aldehyde - e.g., glucose) / Ketoses (ketone - e.g., fructose)
• Examples: Glucose (C₆ aldose), Fructose (C₆ ketose), Galactose, Ribose (C₅)

• Examples: Raffinose, Stachyose (in legumes)

• Homopolysaccharides (one type of sugar):
  • Starch (storage in plants) - amylose + amylopectin
  • Glycogen (storage in animals - liver, muscle)
  • Cellulose (structural in plants)
• Heteropolysaccharides (different types of sugars):
  • Hyaluronic acid, Heparin (anticoagulant), Chondroitin sulfate (cartilage)

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MICROBIOLOGY [6 marks]

Q5. Explain Bacteria Growth Curve

        Log of
        number
        of cells
           |                         ___
           |                       /    \
           |            _________/      \____
           |           /  Stationary
           |   _______/  Exponential
           |  / Lag
           |/_________________________
                        Time →

• No increase in cell number
• Cells are metabolically active - synthesizing enzymes, RNA, adapting to new medium
• Duration depends on medium composition and inoculum size

• Cells divide at maximum rate by binary fission
• Cell number doubles every generation time (doubling time)
• Most metabolically active; most sensitive to antibiotics
• Formula: N = N₀ × 2ⁿ (where n = number of generations)

• Growth rate = Death rate (net zero growth)
• Nutrients depleted, toxic metabolites accumulate
• Spore formation occurs in this phase (e.g., Bacillus, Clostridium)

• Death rate > Growth rate
• Bacteria die due to nutrient exhaustion and toxic waste
• Some cells may persist (viable but non-culturable state)

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Q6. Classify Viruses with Examples

• Icosahedral - Adenovirus, Poliovirus, Rhinovirus
• Helical - Tobacco mosaic virus, Rabies
• Complex - Poxvirus, Bacteriophages

• Enveloped (lipid bilayer): HIV, HSV, Influenza, Hepatitis C, Rabies
• Non-enveloped (Naked): Poliovirus, Adenovirus, Rotavirus, HPV

• Animal viruses (pathogenic to humans)
• Bacteriophages (infect bacteria)
• Plant viruses

• Class I: dsDNA (Herpesvirus, Adenovirus)
• Class II: ssDNA (Parvovirus)
• Class III: dsRNA (Reovirus)
• Class IV: (+) ssRNA (Poliovirus, Hepatitis A)
• Class V: (−) ssRNA (Influenza, Rabies)
• Class VI: ssRNA-RT (HIV - Retroviruses)
• Class VII: dsDNA-RT (Hepatitis B)

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Q7. Different Modes of Transmission of Disease with Examples

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PATHOLOGY [6 marks]

Q8 (circled 5). Cellular Adaptations with Examples

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Q9 (circled 6). Pathophysiology of Edema

Capillary filtration OUT = Capillary hydrostatic pressure (Pc) - Plasma oncotic pressure (πp)
Fluid return IN = Interstitial oncotic pressure (πi) - Interstitial hydrostatic pressure (Pi)

• Venous obstruction, heart failure, portal hypertension
• Fluid pushed out of capillaries into interstitium
• Example: Ankle edema in right heart failure

• Nephrotic syndrome (protein loss in urine), liver cirrhosis (↓ albumin synthesis), malnutrition (kwashiorkor)
• Less fluid drawn back into capillaries

• Inflammation, allergy, histamine, bradykinin
• Protein leaks out → raises interstitial oncotic pressure
• Example: Angioedema, insect bites

• Failure of lymphatics to drain interstitial fluid
• Example: Filariasis (elephantiasis), post-mastectomy arm edema

• Renal failure, hyperaldosteronism
• Increases intravascular volume → increases Pc

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Q10 (circled 7). Tuberculoid vs. Lepromatous Leprosy

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PHARMACOLOGY [8 marks]

Q11 (Q8 in paper). Management of Organophosphorus Poisoning

• Secure airway (risk of bronchospasm + secretions)
• Oxygen supplementation / mechanical ventilation if needed
• Remove contaminated clothing; copious skin/eye washing (decontamination)

• Blocks muscarinic receptors - counteracts SLUDGE effects
• Initial dose: 2-4 mg IV (adults); repeat every 5-10 minutes
• Titration endpoint: drying of secretions (not heart rate)
• May need very large doses (up to 100+ mg in severe cases)

• Reactivates phosphorylated AChE before "aging"
• Dose: 1-2 g IV over 15-30 minutes, then infusion
• Must be given early (within 24-48 hours); ineffective after aging
• Addresses nicotinic effects (muscle weakness, paralysis) that atropine cannot

• For seizure control (diazepam 5-10 mg IV)

• Treat bronchospasm with atropine (not beta-agonists)
• Monitor cardiac rhythm (QTc prolongation risk)
• Correct electrolyte imbalances
• Gastric lavage if oral ingestion within 1 hour

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Q12 (Q9 in paper). Beta-Blockers: Therapeutic Uses and Adverse Effects

• Non-selective: Propranolol, Carvedilol (also α-blocker), Labetalol
• Cardioselective (β₁ selective): Metoprolol, Atenolol, Bisoprolol, Esmolol
• With ISA (intrinsic sympathomimetic activity): Pindolol

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Q13 (Q10 in paper). Receptors: Definition and Types

• Binding opens/closes ion channels directly
• Fast response (milliseconds)
• Examples: Nicotinic ACh receptor (Na⁺/K⁺), GABA-A receptor (Cl⁻), Glutamate (NMDA) receptor

• 7-transmembrane domain receptors
• Linked to Gα, Gβγ subunits → activate second messengers
• Moderate response (seconds-minutes)
• Subtypes:
  • Gs → ↑ adenylyl cyclase → ↑ cAMP (β-adrenergic, D1)
  • Gi → ↓ cAMP (α₂-adrenergic, D2, M2)
  • Gq → ↑ phospholipase C → IP₃ + DAG (M1, M3, α₁, H1)
• Examples: Adrenergic, Muscarinic, Dopamine, Histamine receptors

• Single transmembrane; intracellular domain has enzymatic activity
• Mostly tyrosine kinase activity
• Slow response (hours-days)
• Examples: Insulin receptor, Growth hormone receptor, EGF receptor, IGF receptor

• Located in cytoplasm or nucleus
• Bind lipid-soluble ligands that cross cell membrane
• Regulate gene transcription
• Slowest response (hours-days)
• Examples: Steroid receptors (glucocorticoids, sex hormones), Thyroid hormone receptor, Vitamin D receptor

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Q14 (Q11 in paper). Bioavailability: Definition and Factors Affecting It

• For IV drugs: Bioavailability = 100% (by definition)
• For oral drugs: F = AUC_oral / AUC_IV × 100%

• Tablet disintegration and dissolution rate
• Particle size (smaller = better absorption)
• Polymorphic forms of drug
• Excipients used in formulation

• Lipid solubility - lipophilic drugs cross membranes better
• Molecular size - small molecules absorbed better
• pKa and pH - affects ionization; unionized forms are absorbed
• Chemical stability in GI tract (e.g., penicillin G destroyed by acid)

• Most important factor reducing oral bioavailability
• Drugs absorbed from gut → portal vein → liver → extensively metabolized before reaching systemic circulation
• Examples of high first-pass drugs: Morphine, Propranolol, Lignocaine, GTN, Labetalol

• IV > IM > SC > Sublingual > Oral > Rectal > Topical (generally)
• Sublingual/buccal bypass first-pass (e.g., GTN, buprenorphine)

• Gastric emptying rate (faster = faster absorption)
• GI motility, pH, surface area
• Food-drug interactions (food may ↓ or ↑ bioavailability)
• P-glycoprotein (efflux pump) - reduces absorption

• Enzyme inducers (e.g., rifampicin) → ↓ F
• Enzyme inhibitors (e.g., ketoconazole) → ↑ F
• Chelation (tetracycline + calcium/antacids → ↓ F)

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PHYSIOLOGY [2 marks]

Q15 (Q12 in paper). Saltatory Conduction for Transmission of Action Potential

• Myelinated fibers are covered by Schwann cells (PNS) or oligodendrocytes (CNS) forming a myelin sheath
• Myelin is electrically insulating - prevents ion flow through the membrane
• Nodes of Ranvier are gaps (~1 µm) between adjacent myelin segments where voltage-gated Na⁺ channels are densely concentrated
• The distance between nodes is approximately 1-2 mm (internodal segment)

Action potential at Node 1
        ↓
Local current flows through axoplasm 
(ions cannot cross myelinated segment)
        ↓
Current reaches Node 2 (threshold reached)
        ↓
Na⁺ channels open → Action potential at Node 2
        ↓
Repeats → AP "jumps" to Node 3, 4, 5...

1. Faster conduction velocity - up to 120 m/s in myelinated A-α fibers (vs. 0.5-2 m/s in unmyelinated C-fibers)
2. Energy efficient - Na⁺/K⁺ ATPase only needs to restore ionic gradients at nodes, not along entire axon length
3. Conserves axonal space - allows fast conduction in small diameter fibers

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SECTION B - Clinical Based Questions

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ANATOMY [10 marks]

Q16. Clinical Scenario: 18-year-old girl, short stature, broad chest, webbed neck, underdeveloped genitalia, small uterus, fatty ovaries, primary amenorrhea

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• Non-disjunction in Meiosis I - both homologous chromosomes go to same cell
• Non-disjunction in Meiosis II - sister chromatids fail to separate
• Risk increases with advancing maternal age (especially for trisomy 21)

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Q17. Clinical Scenario: 25-year-old man, swelling of upper limb, road accident 2 months ago, nonunion of fracture humerus, mobility at upper and lower ends of humerus

• Periosteum - the outer fibrous covering of bone is richly supplied by sensory nerve fibers (mainly from somatic nerves). It is the most pain-sensitive structure of bone.
• In nonunion: abnormal mobility at the fracture site stimulates periosteal pain receptors
• Additionally: endosteum (inner lining), medullary vessels also carry nociceptive fibers
• Substance P and prostaglandins released at fracture site sensitize nociceptors

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              HEAD (articulates with glenoid)
             /
    GREATER TUBERCLE (external rotation muscles: IST)
   /
  LESSER TUBERCLE (internal rotation: subscapularis)
  |
  BICIPITAL GROOVE (intertubercular sulcus - long head of biceps)
  |
  SURGICAL NECK ← common fracture site
  |
  SHAFT
  |      ← Radial groove (spiral groove) on posterior surface
  |         (contains radial nerve + profunda brachii artery)
  |
  LOWER END:
  ├── CAPITULUM (lateral) - articulates with radius
  ├── TROCHLEA (medial) - articulates with ulna
  ├── MEDIAL EPICONDYLE (ulnar nerve runs behind it)
  ├── LATERAL EPICONDYLE
  ├── CORONOID FOSSA (anterior, accommodates coronoid process)
  ├── OLECRANON FOSSA (posterior, accommodates olecranon)
  └── RADIAL FOSSA (above capitulum)

• Nonunion of fracture can result from disrupted blood supply, inadequate immobilization, infection, or bone loss
• Fracture of surgical neck can damage axillary nerve and circumflex humeral vessels
• Fracture of shaft (especially mid-shaft) can injure the radial nerve in the spiral groove → wrist drop
• Supracondylar fracture (lower end) can injure the brachial artery → Volkmann's ischemic contracture

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PHYSIOLOGY [10 marks]

Q18. Clinical Scenario: 25-year-old female, dizziness, profuse sweating, rapid pulse, fatigue after outdoor sports on hot day; decreased BP, dry mucous membranes, reduced skin turgor; hypovolemia (heat exhaustion)

• Transfer of heat as infrared electromagnetic waves from body surface to environment
• Does not require direct contact
• Works when environmental temperature < body temperature

• Sweating: sweat evaporates from skin surface (1 g sweat evaporating removes ~0.58 kcal)
• Insensible water loss from lungs and skin
• The ONLY mechanism when environmental temp > body temp
• Crucial in this patient's case (profuse sweating on hot day)

• Transfer of heat to moving air or fluid molecules at skin surface
• Enhanced by wind/fans
• Hot, still day reduces convective cooling

• Direct transfer of heat to cooler objects in contact with the body
• Least important in most situations

• Decreasing metabolic heat production (reduced muscle activity)
• Vasodilation of cutaneous vessels to bring warm blood to surface

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                 ┌─────────────────────────────┐
THERMORECEPTORS  │   HYPOTHALAMUS              │
(skin + blood)   │                             │
     ↓           │  Anterior/Preoptic = COOLING │
Core temp > 37°C →→ CENTER                     │
                 │         ↓                   │
                 │  • Inhibits posterior        │
                 │    (heat conservation)       │
                 │         ↓                   │
                 └─────────────────────────────┘
                           ↓
              Heat Dissipation Responses:
              • ↑ Sweating (cholinergic innervation)
              • Cutaneous vasodilation (↑ blood flow to skin)
              • Behavioral responses (seek cool environment)
              • Inhibition of shivering
              • Tachycardia
              • Panting (in animals)

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Q19. Clinical Scenario: 50-year-old patient, MSA (multiple system atrophy), urinary incontinence, constipation, orthostatic hypotension; impaired bladder/bowel control

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• ↓ Heart rate (negative chronotropy) - via hyperpolarization of SA node (↑ K⁺ conductance)
• ↓ AV node conduction velocity (negative dromotropy) - can cause AV block in excess
• ↓ Atrial contractility (minor effect on ventricles)
• Net effect: Bradycardia and ↓ Blood pressure

• Sphincter pupillae contraction → Miosis (pupil constriction) - mediated by M₃
• Ciliary muscle contraction → lens becomes more convex → Accommodation for near vision (M₃)
• ↑ Aqueous humor drainage (minor)
• Note: Parasympathomimetics (pilocarpine) are used in glaucoma to reduce intraocular pressure

• Detrusor muscle contraction (M₃) → contracts the bladder wall → promotes micturition
• Internal urethral sphincter relaxation (M₃) → allows urine flow
• Net effect: Promotes urination (micturition)

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• Q1-4: Anatomy & Biochemistry (skeletal muscle diagram, melanin, organophosphate biochemistry, carbohydrates)
• Q5-7: Microbiology (bacterial growth curve, virus classification, disease transmission modes)
• Q8-11: Pathology & Pharmacology (cellular adaptations, edema, TB vs. lepromatous leprosy, organophosphate management)
• Q12-15: Pharmacology & Physiology (beta-blockers, receptors, bioavailability, saltatory conduction)
• Q16-17: Clinical Anatomy (Turner syndrome, chromosomal disorders, humerus anatomy/blood supply)
• Q18-19: Clinical Physiology (heat dissipation/thermoregulation, fight-or-flight, parasympathetic effects)