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KATHMANDU UNIVERSITY - BPT Semester I

Paper II: Musculoskeletal System (Upper & Lower Limb)

Complete Answers - All Papers

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SECTION B - SHORT ANSWER QUESTIONS

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ANATOMY

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1. Intrinsic Muscles of the Hand

• Abductor pollicis brevis
• Flexor pollicis brevis
• Opponens pollicis
• (Adductor pollicis - sometimes listed separately)

• Abductor digiti minimi
• Flexor digiti minimi brevis
• Opponens digiti minimi

• 4 Dorsal interossei (DAB - Dorsal ABduct fingers)
• 3 Palmar interossei (PAD - Palmar ADduct fingers)

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2. Boundaries and Contents of the Axilla

• Apex: Bounded by the clavicle, 1st rib, and superior border of scapula
• Base (floor): Axillary fascia and skin
• Anterior wall: Pectoralis major, pectoralis minor, subclavius, clavipectoral fascia
• Posterior wall: Subscapularis, teres major, latissimus dorsi
• Medial wall: Serratus anterior (covering upper ribs)
• Lateral wall: Intertubercular sulcus of humerus

• Axillary artery (1st, 2nd, 3rd parts) with its branches
• Axillary vein
• Brachial plexus (cords and branches)
• Axillary lymph nodes (anterior, posterior, lateral, central, apical)
• Long thoracic nerve (nerve of Bell)
• Intercostobrachial nerve
• Subscapular vessels
• Areolar/fatty tissue

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3. Adductor Magnus - Attachment, Nerve Supply, and Actions

• Adductor part: inferior ramus of pubis and ramus of ischium
• Hamstring part: ischial tuberosity

• Adductor part: medial lip of linea aspera and medial supracondylar line
• Hamstring part: adductor tubercle of medial femoral condyle

• Adductor part: Obturator nerve (L2, L3, L4)
• Hamstring part: Sciatic nerve (tibial part) (L4)

• Adduction of thigh (primary action)
• Medial rotation of thigh (adductor part)
• Extension of thigh (hamstring part)

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4. Formation of Medial Longitudinal Arch of Foot

1. Bony: Shape of the bones (especially talus)
2. Ligaments:
   • Spring ligament (plantar calcaneonavicular) - most important, supports head of talus
   • Long plantar ligament
   • Short plantar (plantar calcaneocuboid) ligament
   • Plantar aponeurosis (most important passive support - "tie-beam")
3. Muscles:
   • Tibialis posterior (main muscle support)
   • Flexor digitorum longus
   • Flexor hallucis longus
   • Intrinsic foot muscles (short plantar muscles)
   • Peroneus longus (from the lateral side)

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5. Abduction of Shoulder Joint

1. 0-90°: Supraspinatus initiates first 15°; deltoid (middle) is the prime mover for 15-90°
2. 90-150°: Scapular rotation (serratus anterior + trapezius = force couple)
3. 150-180°: Lateral flexion of spine

• Supraspinatus (initiates, 0-15°)
• Middle deltoid (15-90°)
• Serratus anterior + Trapezius (scapular rotation, 90-150°)

• At 90°, the greater tuberosity impinges against the acromion - prevented by lateral rotation of humerus
• Supraspinatus is more of a stabilizer (prevents superior subluxation)

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6. Boundaries and Contents of Popliteal Fossa

• Roof (superficial): Skin, superficial fascia, popliteal fascia, small saphenous vein, sural nerve, posterior femoral cutaneous nerve
• Floor (deep): Posterior femur (popliteal surface), oblique popliteal ligament, posterior capsule, popliteus muscle
• Superolateral: Biceps femoris
• Superomedial: Semitendinosus and semimembranosus
• Inferolateral: Lateral head of gastrocnemius + plantaris
• Inferomedial: Medial head of gastrocnemius

• Popliteal artery (deepest)
• Popliteal vein
• Tibial nerve (most superficial)
• Common fibular (peroneal) nerve
• Small saphenous vein (entering the fossa)
• Posterior cutaneous nerve of thigh
• Lymph nodes and fat

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7. Ligaments of Knee Joint (8 Ligaments)

1. Patellar ligament (ligamentum patellae)
2. Medial collateral ligament (tibial)
3. Lateral collateral ligament (fibular)
4. Oblique popliteal ligament
5. Arcuate popliteal ligament

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8. Contents of Cubital Fossa

• Medial: Pronator teres
• Lateral: Brachioradialis
• Base: Imaginary line between medial and lateral epicondyles
• Floor: Brachialis + supinator
• Roof: Deep fascia + bicipital aponeurosis + skin

1. Median nerve
2. Brachial artery (with its bifurcation into radial and ulnar arteries)
3. Biceps tendon (brachii)
4. Radial nerve (and its deep branch) (Plus: recurrent radial artery, fat, lymphatics)

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9. Adductor Compartment of Thigh - Muscles with Nerve Supply

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10. Movements and Muscles at Ankle Joint

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11. Branches of Axillary Artery

1. Superior thoracic artery

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12. Plantar Aponeurosis

• Proximally: Medial process of calcaneal tuberosity
• Distally: Splits into 5 bands → base of proximal phalanges and deep transverse metatarsal ligament

• Maintains medial longitudinal arch (acts as a "tie beam")
• Protects plantar structures
• Acts like a windlass mechanism during push-off (dorsiflexion of toes tightens aponeurosis, raising arch)

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13. Peculiarities/Characteristics of Clavicle

1. First bone to ossify in fetal life (6th week of intrauterine life, intramembranous)
2. Last bone to complete ossification (25 years - medial end epiphysis)
3. Only long bone that ossifies by intramembranous ossification (the sternal end has a secondary epiphysis)
4. No medullary cavity (trabecular bone throughout)
5. Only bone that articulates with the axial skeleton via the sternoclavicular joint
6. Double curve (S-shaped): Medial 2/3 convex forward; lateral 1/3 concave forward
7. Most commonly fractured bone (at junction of middle and outer 1/3)
8. Subclavian vein runs in a groove on its inferior surface

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14. Medial Longitudinal Arch of Foot (formation - see Q4 above for full detail)

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15. Erb's Point and Clinical Relations

• Upper brachial plexus injuries (Erb's palsy) affect C5, C6
• Mechanism: Forcible depression of shoulder with lateral neck flexion (difficult deliveries, motorcycle accidents)
• "Waiter's tip position": Arm adducted, internally rotated, forearm pronated, wrist flexed
• Muscles paralyzed: Deltoid, supraspinatus, infraspinatus, biceps, brachioradialis, supinator
• Loss of: shoulder abduction, external rotation, elbow flexion, forearm supination

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16. Branches of Brachial Plexus (Diagram)

Roots: C5, C6, C7, C8, T1
    ↓
Trunks: Upper (C5,C6), Middle (C7), Lower (C8,T1)
    ↓ (each trunk divides into anterior and posterior division)
Cords: Lateral (ant. div. upper + middle), Posterior (post. div. all 3), Medial (ant. div. lower)
    ↓
Terminal branches:
- Lateral cord: Musculocutaneous nerve + lateral root of median nerve
- Posterior cord: Radial nerve + Axillary nerve
- Medial cord: Ulnar nerve + medial root of median nerve

• Musculocutaneous nerve (C5,C6,C7)
• Axillary nerve (C5,C6)
• Radial nerve (C5-T1)
• Median nerve (C5-T1)
• Ulnar nerve (C8,T1)

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17. Brachial Plexus Well-Labeled Diagram (Feb 2025, Q2)

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18. Short Note on Axilla (KUSMS Internal 2024)

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19. Median Nerve - Short Note

• Recurrent branch (motor to thenar muscles - APB, FPB, opponens pollicis)
• Palmar digital nerves to lateral 3.5 fingers (sensory)
• Motor to lateral 2 lumbricals

• L - Lateral 2 lumbricals
• O - Opponens pollicis
• A - Abductor pollicis brevis
• F - Flexor pollicis brevis

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20. Shoulder Joint - Abduction (see Q5 above)

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21. Lymphatic Drainage of Mammary Gland

• Anterior (pectoral) group: Drains lateral breast
• Central group
• Apical group (final common pathway → subclavian trunk)

• Interpectoral (Rotter's) nodes
• Posterior intercostal lymphatics
• Subdiaphragmatic: to liver (Gerota's pathway)
• Cross drainage to contralateral breast

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22. 1st Carpometacarpal (CMC) Joint

• Type: Saddle joint (bicondylar/sellar)
• Bones: Trapezium + base of 1st metacarpal
• Movements: Flexion/extension, abduction/adduction, circumduction, opposition (most mobile CMC joint)
• Ligaments: Anterior oblique, posterior oblique, radial, ulnar ligaments
• Clinical: Osteoarthritis here = "Bennett's fracture" area; joint laxity leads to CMC OA (common in post-menopausal women)

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23. Radial Nerve - Formation, Course, Distribution

1. Axilla: Behind axillary artery, in front of subscapularis
2. Arm: Spiral groove of humerus (with profunda brachii artery)
3. Lateral side of arm: Pierces lateral intermuscular septum
4. Anterior to lateral epicondyle: Divides into superficial (sensory) and deep (posterior interosseous nerve)

• In arm: Triceps, anconeus, brachioradialis, ECRL
• In forearm: ECRB, supinator, finger extensors (via PIN)

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24. Formation of Carpal Tunnel

• Medial attachment: Pisiform and hook of hamate
• Lateral attachment: Scaphoid tubercle and trapezium

1. Flexor digitorum superficialis tendons (×4) - superficial and middle
2. Flexor digitorum profundus tendons (×4) - deep
3. Flexor pollicis longus tendon (×1)
4. Median nerve (most superficially placed and most vulnerable)

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25. Inguinal Ligament - Attachments, Triangle, Contents

• Base: Inguinal ligament
• Medial: Medial border of adductor longus
• Lateral: Medial border of sartorius
• Floor: Iliopsoas, pectineus, adductor longus
• Roof: Fascia lata + cribriform fascia

• Nerve (femoral) - lateral
• Artery (femoral)
• Vein (femoral)
• Empty space (femoral canal - medial compartment - site of femoral hernia)
• Lymphatics (in femoral canal)

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26. Knee Joint - Articulating Bones, Ligaments, Movements

• Flexion (0-130°): Hamstrings, gracilis, sartorius, popliteus
• Extension (0-10° hyperextension): Quadriceps femoris
• Medial rotation (unlocking): Popliteus
• Lateral rotation (locking in full extension): ITB, biceps femoris

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27. Supracondylar Ridges of Humerus - Muscular Attachments

• Brachialis (partially)
• Coracobrachialis (partial)
• Medial head of triceps

• Brachioradialis
• Extensor carpi radialis longus (ECRL)
• Lateral head of triceps proximally

• Caused by compartment syndrome after supracondylar fracture of humerus
• Ischaemia → fibrosis of forearm flexor muscles (flexor digitorum superficialis, profundus, flexor pollicis longus)
• Results in: Forearm pronated, wrist and fingers flexed (characteristic posture)
• Brachial artery branches: Profunda brachii, superior ulnar collateral, inferior ulnar collateral, anterior ulnar recurrent, posterior ulnar recurrent, radial artery, ulnar artery

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BIOCHEMISTRY

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28. Uric Acid and Related Disease

• End product of purine (adenine and guanine) metabolism in humans
• Formed by xanthine oxidase action on xanthine and hypoxanthine
• Normal serum level: 3.5-7.0 mg/dL (men), 2.5-6.0 mg/dL (women)
• Mostly excreted by kidneys (70%) and gut (30%)

• Deposition of monosodium urate (MSU) crystals in joints and soft tissues
• Types: Primary gout (overproduction or underexcretion) vs Secondary gout
• Acute gout: Intense inflammatory arthritis, commonly 1st MTP joint (podagra)
• Chronic tophaceous gout: Tophi in ear helix, tendons, skin
• Crystals: Needle-shaped, negatively birefringent under polarized light
• Pathogenesis: Hyperuricaemia → crystal deposition → neutrophil phagocytosis → IL-1β release → inflammation

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29. Cori Cycle (Importance)

1. Muscle undergoes anaerobic glycolysis → Pyruvate → Lactate
2. Lactate released into blood → transported to liver
3. In liver: Lactate → Pyruvate (lactate dehydrogenase) → Gluconeogenesis → Glucose
4. Glucose released back into blood → taken up by muscle

• Removes lactate from muscles (prevents acidosis and fatigue)
• Recycles carbon for new glucose production
• Maintains blood glucose during exercise
• Glucose-sparing effect for the brain
• Links anaerobic (muscle) and aerobic (liver) metabolism

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30. Creatine Phosphate (Phosphocreatine)

1. Arginine + Glycine → Guanidinoacetate + Ornithine (enzyme: AGAT, in kidney)
2. Guanidinoacetate + SAM → Creatine + SAH (enzyme: GAMT, in liver)
3. Creatine → transported to muscle → Creatine kinase adds phosphate → Phosphocreatine

• Immediate ATP reserve (Lohmann reaction): Phosphocreatine + ADP ⇌ Creatine + ATP
• First energy source used during sudden intense exercise (first 5-10 seconds)
• Creatinine is spontaneous degradation product of creatine → excreted in urine (marker of GFR)

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31. Role of PTH and Calcitriol in Calcium Homeostasis

• Secreted in response to low serum Ca²⁺
• Actions:
  • Bone: Stimulates osteoclast activity → Ca²⁺ and PO₄³⁻ release
  • Kidney: Increases Ca²⁺ reabsorption in DCT; decreases phosphate reabsorption; activates 1-alpha hydroxylase
  • Gut: Indirect (via calcitriol synthesis)
• Net effect: ↑ serum Ca²⁺, ↓ serum PO₄³⁻

• Synthesized: Skin (UV) → Cholecalciferol → 25-OH in liver → 1,25(OH)₂D₃ by 1-alpha hydroxylase in kidney (PTH stimulates this step)
• Actions:
  • Gut: Increases Ca²⁺ and PO₄³⁻ absorption (main action)
  • Bone: Works with PTH on osteoclasts
  • Kidney: Mild increase in Ca²⁺ reabsorption
• Net effect: ↑ serum Ca²⁺ and ↑ serum PO₄³⁻

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32. ATP Sources for Skeletal Muscle Contraction

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33. Hormones in Calcium Homeostasis (Short Answer)

• Calcitonin (from thyroid C cells): Opposes PTH; inhibits osteoclasts; lowers Ca²⁺
• Estrogen/Androgens: Inhibit bone resorption
• Glucocorticoids: Decrease intestinal Ca²⁺ absorption; increase renal excretion (→ osteoporosis)

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MICROBIOLOGY

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34. Pathogenesis of Osteomyelitis

• Most common overall: Staphylococcus aureus
• Neonates: Group B Streptococcus, S. aureus
• Sickle cell: Salmonella (classically) + S. aureus
• Post-surgical/trauma: S. aureus, gram-negative rods
• Immunocompromised: Pseudomonas, fungi

1. Bacteremia → seeding of metaphysis (rich blood supply, slow sinusoidal flow, lack of phagocytes)
2. Bacteria multiply → acute inflammation → pus formation
3. Pus spreads under periosteum → subperiosteal abscess → strips periosteum → avascular necrosis
4. Dead bone = sequestrum (surrounded by pus and granulation tissue)
5. Periosteum lays down new bone = involucrum (shell of new bone around sequestrum)
6. Channels in involucrum = cloacae (drain pus)
7. Sinus tract formation to skin
8. Chronic osteomyelitis if untreated

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35. Types of Leprosy (Ridley-Jopling Classification)

• Paucibacillary (PB): ≤5 lesions → Rifampicin + Dapsone (6 months)
• Multibacillary (MB): >5 lesions → Rifampicin + Clofazimine + Dapsone (12 months)

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PATHOLOGY

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36. Morphology of Osteosarcoma

• Large, destructive tumor, crosses epiphyseal plate (but rare in epiphysis)
• Grey-white, hemorrhagic, necrotic
• Codman's triangle: Periosteal elevation (reactive bone)
• Sunburst pattern on X-ray: Perpendicular spicules of reactive bone

• Malignant pleomorphic spindle cells (osteoblasts) producing osteoid (woven bone) - HALLMARK
• Bizarre mitoses, nuclear atypia
• May have chondroblastic or fibroblastic areas
• Necrosis common

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37. Etiopathogenesis of Pott's Spine (Spinal Tuberculosis)

1. Primary pulmonary TB → hematogenous spread to vertebral body (via Batson's plexus or systemic arterial spread)
2. Bacilli settle in anterior part of vertebral body (near disc, blood-rich)
3. Infection spreads to adjacent disc → disc destruction (TB destroys discs, unlike pyogenic which also does but later; distinguishing: in pyogenic, disc preserved early)
4. Caseous necrosis of vertebral body → vertebral collapse → kyphosis/gibbus
5. Cold abscess: Pus collects → does NOT produce heat/redness (hence "cold")
   • Thoracic: Paraspinal abscess → tracks along posterior mediastinum
   • Lumbar: Psoas abscess → tracks to groin/iliac fossa → presenting in femoral triangle
6. Cord compression → paraplegia (Pott's paraplegia)

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38. Clinical Features and Complications of Rheumatoid Arthritis

• Morning stiffness >1 hour
• Symmetrical polyarthritis (MCP, PIP joints - spares DIP)
• Swelling, warmth, tenderness
• Deformities: Swan neck, boutonniere, ulnar deviation, Z-thumb

• Fever, fatigue, anorexia, weight loss
• Rheumatoid nodules (subcutaneous, at pressure points)
• Anemia of chronic disease
• Felty's syndrome (RA + splenomegaly + leukopenia)

1. Articular: Joint destruction, atlantoaxial subluxation (C1-C2 → cervical myelopathy)
2. Cardiac: Pericarditis, myocarditis, valvular lesions
3. Pulmonary: Pleuritis, rheumatoid nodules, fibrosing alveolitis
4. Ocular: Episcleritis, scleritis, keratoconjunctivitis sicca (secondary Sjogren's)
5. Neurological: Mononeuritis multiplex, carpal tunnel syndrome
6. Renal: Secondary amyloidosis (AA amyloid)
7. Vascular: Vasculitis
8. Hematological: Anemia, thrombocytosis

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39. Fracture - Definition, Types

• Traumatic (most common)
• Stress/fatigue fracture (repeated loading)
• Pathological (diseased bone - osteoporosis, tumor)

• Closed (simple): Skin intact
• Open (compound): Communicates with external environment (infection risk)

• Transverse: Perpendicular to long axis
• Oblique: Angled
• Spiral: Twisting force
• Comminuted: Fragmented into >2 pieces
• Greenstick: Incomplete (children; cortex on one side intact)
• Impacted: Ends driven into each other

• Undisplaced / Displaced

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40. Fracture Healing

1. Hematoma formation (0-48 hrs): Bleeding, clot formation; inflammatory mediators release
2. Fibrocartilaginous callus (Days 3-7): Fibroblasts and chondroblasts invade; cartilaginous bridge
3. Bony (hard) callus (Weeks 3-12): Endochondral ossification; woven bone formed
4. Remodeling (Months to years): Woven bone → lamellar bone; medullary canal restored

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41. Pott's Disease - see Q37 above

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42. Duchene Muscular Dystrophy

• Onset: 2-5 years; boys
• Proximal muscle weakness (Gower's sign - uses hands to climb up own legs to stand)
• Pseudohypertrophy of calves (fibrofatty replacement)
• Waddling gait, lumbar lordosis
• Cardiac involvement (dilated cardiomyopathy)
• Progressive: wheelchair by age 12; death by 20-25 (respiratory failure)

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43. Differences between Osteoporosis and Osteoarthritis

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44. Characteristic Morphology of Osteoclastoma (Giant Cell Tumor)

• Uniformly distributed multinucleate giant cells (osteoclast-like) in a background of spindle-shaped mononuclear stromal cells
• Nuclei of giant cells identical to stromal cells (key feature)
• Hemorrhagic areas common

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PHARMACOLOGY

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45. Ibuprofen - Therapeutic Uses and Adverse Effects

1. Mild-moderate pain (headache, dental pain, dysmenorrhoea)
2. Fever (antipyretic)
3. Rheumatoid arthritis, osteoarthritis (anti-inflammatory)
4. Patent ductus arteriosus closure in neonates
5. Ankylosing spondylitis

1. GI: Nausea, dyspepsia, peptic ulcer, GI bleeding (inhibits PGE₂/PGI₂ that protect gastric mucosa)
2. Renal: Decreased GFR, fluid retention, acute kidney injury (especially in volume-depleted patients)
3. Cardiovascular: Increased risk of MI/stroke (especially COX-2 selective NSAIDs)
4. Platelet: Reversibly inhibits platelet aggregation (temporary prolonged bleeding time)
5. Hypersensitivity: Aspirin-sensitive asthma (can trigger bronchospasm)
6. CNS: Headache, dizziness (rare)

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46. DMARDs (Disease-Modifying Anti-Rheumatic Drugs)

1. Methotrexate (gold standard, most used first-line)
2. Hydroxychloroquine
3. Sulfasalazine
4. Leflunomide
5. Gold salts (historical)
6. D-penicillamine (historical)
7. Azathioprine

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47. Aspirin - Mechanism and Important Adverse Effects

• Irreversible inhibition of COX-1 and COX-2 (acetylates serine residue)
• Reduces prostaglandins (PGE₂, PGF₂α, PGI₂) and thromboxane (TXA₂)
• At low doses: selectively inhibits platelet COX-1 → inhibits TXA₂ → antiplatelet effect (irreversible for 7-10 days - platelet lifespan)
• At high doses: Also inhibits PGI₂ in vessel walls; antipyretic, anti-inflammatory

1. GI irritation, ulcers, bleeding
2. Reye's syndrome (children with viral illness - encephalopathy + liver failure - CONTRAINDICATED in children <16)
3. Aspirin-sensitive asthma (bronchoconstriction via LTs)
4. Salicylism (tinnitus, dizziness, hearing loss at high doses)
5. Respiratory alkalosis → metabolic acidosis (high dose toxicity)
6. Hypoglycemia (high doses)
7. Antiplatelet (beneficial for cardiovascular; bleeding risk for surgery)

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48. Allopurinol - Mechanism and Adverse Effects

• Structural analog of hypoxanthine
• Inhibits xanthine oxidase (enzyme that converts hypoxanthine → xanthine → uric acid)
• Its active metabolite oxypurinol is the main inhibitor
• Reduces uric acid synthesis → prevents gout, urate nephropathy, tumor lysis syndrome

1. Hypersensitivity reactions: Maculopapular rash (most common); severe: DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), Stevens-Johnson syndrome (especially with HLA-B*5801 in Asian populations)
2. GI upset, nausea
3. Drug interactions: Azathioprine/6-MP toxicity (allopurinol inhibits their metabolism by xanthine oxidase → dose must be reduced by 75%)
4. Acute gout flare at initiation (mobilization of urate deposits)
5. Hepatotoxicity (rare)
6. Xanthine and oxypurinol urolithiasis (rare)

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49. Drugs Used in Leprosy (MDT)

• Rifampicin 600 mg once monthly (supervised)
• Dapsone 100 mg daily

• Rifampicin 600 mg once monthly (supervised)
• Clofazimine 300 mg once monthly + 50 mg daily
• Dapsone 100 mg daily

• Rifampicin: Bactericidal; inhibits bacterial RNA polymerase; red-orange urine/secretions
• Dapsone: Bacteriostatic; inhibits folate synthesis; adverse: hemolytic anemia, methemoglobinemia
• Clofazimine: Bactericidal + anti-inflammatory; adverse: skin hyperpigmentation (red-brown), GI effects

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50. Drugs in Chronic Gout

1. Allopurinol (xanthine oxidase inhibitor - uric acid synthesis inhibitor)
2. Febuxostat (selective xanthine oxidase inhibitor; preferred in renal impairment)
3. Probenecid (uricosuric - inhibits renal tubular reabsorption of urate)
4. Rasburicase (recombinant uricase; converts uric acid to allantoin; used in tumor lysis)
5. Colchicine (acute gout attack prevention; also for prophylaxis)
6. NSAIDs (for acute attacks; not for chronic)

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PHYSIOLOGY

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51. Sarcomere of Skeletal Muscle (Well-Labeled Diagram)

Z line — I band — A band (with H zone + M line in center) — I band — Z line

|←————————— One SARCOMERE ——————————→|
Z    I        A        (H)  M  (H)        A        I    Z

• Z line (Z disc): Anchors thin filaments; defines sarcomere boundary
• I band: Only thin (actin) filaments; bisected by Z line; appears LIGHT; shortens during contraction
• A band: Thick (myosin) filaments + overlapping actin; appears DARK; does NOT shorten
• H zone: Only thick (myosin) filaments in center of A band; disappears during contraction
• M line: Middle of H zone; cross-links myosin filaments
• Thin filaments: Actin + tropomyosin + troponin complex (TnT, TnI, TnC)
• Thick filaments: Myosin (heavy chains forming heads and tails)

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52. Excitation-Contraction (E-C) Coupling in Skeletal Muscle

1. Action potential travels along motor neuron → reaches neuromuscular junction
2. ACh release: Depolarization → Ca²⁺ influx through VGCCs → ACh vesicles fuse → ACh released into synaptic cleft
3. Motor end plate depolarization: ACh binds nicotinic receptors → Na⁺ influx → end plate potential (EPP) → triggers action potential in muscle
4. T-tubule conduction: Action potential spreads along sarcolemma → enters T-tubules (invaginations at A-I junction)
5. DHPR activation: Voltage-sensitive dihydropyridine receptors (L-type Ca²⁺ channels) in T-tubule sense depolarization
6. RyR activation: DHPR mechanically activates ryanodine receptors (RyR1) on sarcoplasmic reticulum (SR) → massive Ca²⁺ release from SR
7. Troponin binding: Ca²⁺ binds troponin C (TnC) → conformational change in troponin-tropomyosin complex → tropomyosin shifts to expose actin-myosin binding sites
8. Cross-bridge cycling:
   • Myosin head (with ATP hydrolysis products ADP + Pi) binds actin → power stroke → filaments slide
   • ATP binds myosin head → detachment → hydrolysis → re-cocking → repeat
9. Relaxation: Ca²⁺ pumped back into SR by SERCA (Ca²⁺-ATPase); tropomyosin re-covers binding sites; muscle relaxes

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53. Differences: Red vs White Muscle Fibers

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54. Neuromuscular Transmission - Steps

1. Action potential reaches axon terminal
2. Depolarization opens voltage-gated Ca²⁺ channels (VGCCs)
3. Ca²⁺ influx → ACh vesicle fusion with presynaptic membrane (SNARE proteins)
4. ACh released into synaptic cleft
5. ACh diffuses across cleft and binds to nicotinic ACh receptors (nAChR - ligand-gated ion channels) on motor end plate
6. Na⁺ influx (and some K⁺ efflux) → End Plate Potential (EPP)
7. EPP triggers action potential in adjacent sarcolemma
8. ACh degraded by acetylcholinesterase (AChE) → choline + acetate
9. Choline recycled into presynaptic terminal

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55. Isometric vs Isotonic Muscle Contraction

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56. End Plate Potential (EPP)

• Produced by binding of ACh to nicotinic receptors → simultaneous opening of Na⁺ and K⁺ channels
• Unlike action potential: it is GRADED (not all-or-none), localized, cannot propagate
• Normal EPP is suprathreshold → triggers action potential in surrounding sarcolemma
• Miniature EPP (MEPP): Spontaneous quantal release of single ACh vesicle → tiny depolarization (~0.5 mV)
• AChE rapidly hydrolyzes ACh → EPP is brief

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57. Types of Nerve Injury (Seddon Classification)

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58. Strength-Duration Curve

• As pulse duration increases, less current is needed
• Rheobase: Minimum current (intensity) required regardless of time (infinite duration) - the horizontal asymptote
• Chronaxie: Duration of stimulus at twice rheobase intensity - measures nerve/muscle excitability
• Normal nerve: Chronaxie = 0.01-1 ms (short)
• Denervated muscle: Chronaxie increases (less excitable)
• Used clinically to detect denervation and guide electrotherapy

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59. Role of ATP and Ca²⁺ in Skeletal Muscle Contraction

• Trigger: Ca²⁺ released from SR binds troponin C → exposes myosin-binding sites on actin → cross-bridge formation possible
• Regulation: Calcium is the ON/OFF switch for contraction (cross-bridges cannot form without it)

1. Energy for power stroke: ATP hydrolysis by myosin ATPase → ADP + Pi → conformational change → power stroke
2. Cross-bridge detachment: ATP binds myosin head → dissociates actin-myosin complex (rigor mortis when ATP depleted)
3. Ca²⁺ pumping: SERCA (SR Ca²⁺-ATPase) uses ATP to pump Ca²⁺ back into SR → relaxation
4. Na⁺/K⁺ ATPase: Maintains membrane potential

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60. Molecular Basis of Skeletal Muscle Contraction and Relaxation

• Thick (myosin) and thin (actin) filaments slide past each other; neither shortens
• Myosin heads bind actin, undergo power strokes, detach, and repeat → progressive sliding

1. Myosin head + ADP + Pi in "cocked" position → binds actin (cross-bridge formed)
2. Power stroke: Pi released → myosin head pivots 45° → actin pulled toward M line
3. ADP released → rigor state
4. Detachment: ATP binds myosin head → dissociates from actin
5. Re-cocking: ATP hydrolyzed → myosin re-cocked → cycle repeats

• Action potential ceases → no more Ca²⁺ release
• SERCA pumps Ca²⁺ back into SR (requires ATP)
• Ca²⁺ dissociates from TnC → tropomyosin moves back → blocks actin binding sites
• Cross-bridges detach when available sites blocked → muscle lengthens passively

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CLINICAL BASED QUESTIONS

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Q16 (Aug 2024): Carpal Tunnel Syndrome Case

1. Lateral 2 lumbricals (1st and 2nd)
2. Opponens pollicis
3. Abductor pollicis brevis
4. Flexor pollicis brevis (superficial head) (Recurrent branch of median nerve = most important motor branch in hand)

• Palmar surface: Lateral 3.5 fingers (thumb, index, middle, lateral half ring)
• Dorsal surface: Distal phalanges of same 3.5 fingers
• Skin of thenar eminence (via palmar cutaneous branch - passes ABOVE flexor retinaculum, so NOT compressed in CTS)

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Q17 (Aug 2024): Gluteal Injection Nerve Injury Case

• Hamstrings (tibial part of sciatic): Biceps femoris (long head), semitendinosus, semimembranosus
• Biceps femoris short head (common peroneal part of sciatic)
• Adductor magnus (hamstring part, tibial nerve)

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Q18 (Aug 2024 / Feb 2025): Hypocalcaemia / Anxiety Hyperventilation

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Q19 (Aug 2024): Myasthenia Gravis / Fatigue

1. Central fatigue: Reduced motor drive from CNS; accumulation of serotonin; psychological factors
2. Peripheral/muscle fatigue:
   • Depletion of ATP and phosphocreatine
   • Lactate and H⁺ accumulation → inhibit myosin ATPase, inhibit Ca²⁺ release
   • Reduced Ca²⁺ release from SR
   • Inorganic phosphate (Pi) accumulation → reduces force of cross-bridge
   • Glycogen depletion
3. NMJ fatigue: Depletion of ACh vesicles (rare in normal conditions, prominent in MG)

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Q7 (March 2023): Ankle Sprain - Ligament and Movements

1. Anterior talofibular ligament (ATFL) - most commonly torn (weakest)
2. Calcaneofibular ligament (CFL)
3. Posterior talofibular ligament (PTFL) - strongest; rarely torn

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Q8 (March 2023 / Internal 2024): Carpal Tunnel - Ape Hand

• 4 tendons of FDS
• 4 tendons of FDP
• 1 tendon of FPL
• Median nerve (Total: 9 tendons + 1 nerve)

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Q9 (March 2023): Hyperventilation - NMJ Transmission and Muscle Fibers

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Q10 (March 2023): Biceps Wasting - Nerve Injury and Strength-Duration Curve

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Clinical - Brachial Plexus Injury (Internal 2024 Q1)

• Arises from medial cord of brachial plexus (C8, T1)
• Runs medial to brachial artery in arm → passes posterior to medial epicondyle ("funny bone")
• Enters forearm between two heads of FCU
• Descends on medial side → enters hand via Guyon's canal (lateral to pisiform)

• In forearm: Flexor carpi ulnaris (FCU), medial half of FDP (ring and little fingers), dorsal cutaneous branch
• In hand:
  • Superficial: Palmaris brevis; skin of medial 1.5 fingers
  • Deep: Hypothenar muscles (ADM, FDM, ODM), all dorsal interossei (×4), palmar interossei (×3), medial 2 lumbricals (3rd and 4th), adductor pollicis, deep head of FPB

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Clinical - Inguinal Triangle (Internal 2024 Q2)

• Medial: Lateral border of rectus abdominis
• Lateral: Inferior epigastric artery
• Inferior: Inguinal ligament
• Contents: Direct inguinal hernia passes through this triangle (medial to inferior epigastric artery)

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Clinical - Knee Joint (KUSMS Internal - Mrs. Shrestha)

• Extracapsular: Patellar ligament, MCL, LCL, oblique popliteal, arcuate popliteal
• Intracapsular (extrasynovial): ACL, PCL; also transverse ligament, meniscofemoral ligaments

• Flexion: Hamstrings (biceps, semitendinosus, semimembranosus), gastrocnemius, popliteus, gracilis, sartorius
• Extension: Quadriceps (rectus femoris, VMO, VL, VI)
• Medial rotation: Popliteus (unlocking), semitendinosus, semimembranosus
• Lateral rotation: Biceps femoris

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Clinical - Eversion of Foot (Feb 2025 Q16)

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Bells' Palsy / Brachial Birth Palsy (Klumpke's / Erb's)

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SUMMARY TABLE OF HIGH-YIELD MNEMONICS

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Quick Navigation Guide

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KATHMANDU UNIVERSITY - May/June 2022

Paper I: Basic Concepts, Genetics, Integumentary & Autonomic Nervous System

Section B - Short Answer Questions

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ANATOMY

1. Well-Labelled Diagram of Thin Skin

SURFACE
─────────────────────────────────
Stratum corneum     (dead, keratinized cells)
─────────────────────────────────
Stratum granulosum  (keratohyalin granules)
─────────────────────────────────
Stratum spinosum    (prickle cells, desmosomes)
─────────────────────────────────
Stratum basale      (stem cells, melanocytes)
─────────────────────────────────
DERMIS (papillary → reticular)
─────────────────────────────────
Subcutaneous tissue (hypodermis)

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BIOCHEMISTRY

2. Define and Classify Lipids [1+2=3]

• Fats (triglycerides/triacylglycerols): Glycerol + 3 fatty acids
• Waxes: Long-chain alcohol + fatty acid

• Phospholipids: Glycerophospholipids (lecithin, cephalin, plasmalogen) + Sphingomyelin
• Glycolipids (cerebrosides, gangliosides): Lipid + carbohydrate
• Lipoproteins: Lipid + protein (chylomicrons, VLDL, LDL, HDL)

• Fatty acids (saturated, unsaturated)
• Sterols (cholesterol, bile acids, steroid hormones, vitamin D)
• Fat-soluble vitamins (A, D, E, K)
• Ketone bodies

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3. Prokaryotic Replication with Diagram [3]

• Circular, double-stranded DNA
• Single origin of replication: oriC (origin of replication chromosome)
• Bidirectional (two replication forks move in opposite directions)
• Semiconservative (each new molecule has one old + one new strand)

1. Initiation: DnaA protein binds oriC → DNA helicase (DnaB) unwinds the double helix → single-strand binding (SSB) proteins stabilize
2. Primer synthesis: Primase (DnaG) synthesizes short RNA primers
3. Elongation:
   • DNA Pol III (main enzyme): 5'→3' synthesis; 3'→5' exonuclease (proofreading)
   • Leading strand: continuous synthesis
   • Lagging strand: Okazaki fragments (discontinuous)
4. Removal of primers: DNA Pol I (5'→3' exonuclease) removes RNA primers, fills gaps
5. Joining: DNA ligase seals nicks between Okazaki fragments

oriC
 ↓
→→→→→→→→ (leading)
←←←←←←←← (lagging, Okazaki fragments)

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MICROBIOLOGY

4. Differentiating Characters Between Bacteria and Viruses [3]

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5. Causative Agent of Leprosy and Classification [1+2]

• Acid-fast bacillus (AFB)
• Obligate intracellular parasite (Schwann cells and macrophages)
• Cannot be cultured in vitro (grown in armadillo footpad)
• Slow growing (doubling time ~12-13 days)
• Optimal temperature: 27-30°C (peripheral nerves - cooler areas)

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PATHOLOGY

6. Difference Between Apoptosis and Necrosis [2]

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7. Types of Cell Adaptations with Examples [2]

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8. Difference Between Acute and Chronic Inflammation [2]

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PHARMACOLOGY

9. Plasma Half-Life; Zero Order and First Order Kinetics [2+2]

• Time taken for plasma concentration of a drug to fall by 50%
• Formula: t½ = 0.693 / Ke (Ke = elimination rate constant)
• Also: t½ = (0.693 × Vd) / CL (Vd = volume of distribution, CL = clearance)
• Clinical importance:
  • Determines dosing frequency
  • After 4-5 half-lives: steady state achieved
  • After 4-5 half-lives: drug essentially eliminated (97%)

• Rate of elimination is proportional to plasma drug concentration
• A constant fraction of the drug is eliminated per unit time
• t½ is constant (independent of dose)
• Most drugs follow this (therapeutic doses)
• Graph: exponential decline in plasma concentration vs time
• Example: paracetamol, most antibiotics

• Rate of elimination is constant regardless of plasma concentration (saturation kinetics)
• A constant amount eliminated per unit time
• t½ is NOT constant (increases with dose)
• Enzymes saturated - small dose increase → disproportionate rise in levels (toxic!)
• Examples: Alcohol (ethanol), Phenytoin (at high doses), Aspirin (high doses)

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10. Cholinergic Drugs - Uses and Adverse Effects [2+1+1]

• Direct: Bind muscarinic/nicotinic receptors
  • Muscarinic agonists: Pilocarpine, Bethanechol, Carbachol
  • Nicotinic agonists: Nicotine (not therapeutic)
• Indirect (AChE inhibitors): Inhibit acetylcholinesterase → ↑ ACh
  • Reversible: Neostigmine, Pyridostigmine, Physostigmine, Donepezil
  • Irreversible: Organophosphates (nerve agents, insecticides)

1. Glaucoma (Pilocarpine - constricts pupil, opens trabecular meshwork)
2. Myasthenia gravis (Neostigmine, Pyridostigmine - increase NMJ ACh)
3. Atony of GI/bladder after surgery (Bethanechol)
4. Alzheimer's disease (Donepezil, Rivastigmine, Galantamine)
5. Reversal of non-depolarizing NMJ blockers (Neostigmine)
6. Glaucoma, xerostomia (Pilocarpine)

• S - Salivation (excessive)
• L - Lacrimation
• U - Urination (incontinence)
• D - Defecation/Diarrhea
• G - GI cramps
• E - Emesis (vomiting)
• Also: Bradycardia, bronchoconstriction, miosis, sweating

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PHYSIOLOGY

11. Four Differences Between Parasympathetic and Sympathetic Nervous System [2]

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CLINICAL BASED QUESTIONS (from last exam in image 9)

Clinical Anatomy - Mrs. Shrestha (Knee Osteoarthritis)

• Distal end of femur (medial + lateral condyles)
• Proximal end of tibia (medial + lateral condyles)
• Patella (with femur - patellofemoral joint)

1. Patellar ligament (ligamentum patellae)
2. Medial (tibial) collateral ligament
3. Lateral (fibular) collateral ligament
4. Oblique popliteal ligament
5. Arcuate popliteal ligament

1. Anterior cruciate ligament (ACL) - prevents anterior tibial glide
2. Posterior cruciate ligament (PCL) - prevents posterior tibial glide

• Flexion: Biceps femoris, semitendinosus, semimembranosus, gastrocnemius, popliteus, gracilis, sartorius
• Extension: Quadriceps femoris (rectus femoris, vastus medialis, lateralis, intermedius)

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Clinical - Raju Shah (Supracondylar Fracture + Volkmann's)

• Medial head of triceps
• Coracobrachialis (distal)

• Brachioradialis
• Extensor carpi radialis longus (ECRL)
• Lateral head of triceps

• Caused by compartment syndrome following supracondylar fracture of humerus in children
• Brachial artery kinking/injury → ischaemia of anterior forearm compartment
• Ischaemia → fibrosis of flexor muscles (FDS, FDP, FPL)
• Classic posture: Forearm pronated, wrist flexed, fingers flexed at IP joints (characteristic contracture deformity)
• Treatment: Emergency fasciotomy (if acute); late: Z-plasty, tendon lengthening

1. Profunda brachii (deep brachial artery)
2. Superior ulnar collateral artery
3. Inferior ulnar collateral artery
4. Nutrient artery to humerus
5. Radial artery (terminal branch at cubital fossa)
6. Ulnar artery (terminal branch at cubital fossa)

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Clinical Physiology - Myasthenia Gravis (Rani Maiya)

• Antibodies block/destroy nAChR → reduced end plate potential → fatigable muscle weakness
• Hallmarks: Fluctuating, fatigable weakness (worse with activity, better with rest); bilateral ptosis and diplopia (ocular muscles first)
• Associated with thymic hyperplasia or thymoma
• Diagnosis: Anti-AChR antibodies, Tensilon (edrophonium) test, repetitive nerve stimulation (decremental response)
• Treatment: Pyridostigmine (AChE inhibitor), immunosuppression (steroids, azathioprine), thymectomy, plasma exchange/IVIG in crisis

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Clinical Physiology - Asthma Patient (ATP/Ca²⁺ and Type I vs Type II Muscle Fibers)

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Newborn Brachial Plexus Injury (Klumpke's/Erb's)

• Mechanism: Widening of angle between head and shoulder (forcible lateral neck flexion away from shoulder)
• Nerves affected at Erb's point: C5, C6 (upper trunk of brachial plexus)
• Position ("Waiter's tip"):
  • Shoulder: adducted, internally rotated
  • Elbow: extended
  • Forearm: pronated
  • Wrist: flexed
• Muscles paralyzed: Deltoid, supraspinatus, infraspinatus, teres minor, biceps, brachioradialis, supinator

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QUICK REFERENCE SUMMARY