BP101T Human Anatomy and Physiology I — GPAT Question Bank

✔ Correct — B: Mitochondria — double-membrane organelle (outer smooth, inner folded into cristae); site of ATP synthesis via oxidative phosphorylation (Krebs cycle in matrix + electron transport chain on inner membrane). Has own circular DNA (mtDNA, maternally inherited, 37 genes, 16 569 bp human), 70S ribosomes; endosymbiotic origin (α-proteobacterial). Produces 30-32 ATP per glucose. Rich in muscle + liver + brown adipose tissue (uncoupling protein UCP-1 for thermogenesis). Dysfunction → mitochondrial diseases (MELAS, MERRF, Leber hereditary optic neuropathy).

✔ Correct — A: Fluid Mosaic Model — S.J. Singer + Garth Nicolson (1972). Describes plasma membrane as phospholipid bilayer (~ 7.5 nm) with embedded + peripheral proteins that can move laterally. Components: phospholipids (phosphatidylcholine, phosphatidylethanolamine, sphingomyelin), cholesterol (rigidity + fluidity control), integral (transmembrane) + peripheral proteins, glycolipids + glycoproteins (on outer leaflet — glycocalyx, cell recognition). Asymmetric distribution: PS on inner leaflet (flipped out in apoptosis → eat-me signal). Lipid rafts = cholesterol + sphingolipid-rich domains for signalling.

✔ Correct — C: Osmosis — net passive movement of water from area of lower solute concentration (hypotonic) to higher solute concentration (hypertonic) across a semipermeable membrane. Water channels: aquaporins (AQP1 RBC + kidney PT; AQP2 collecting duct regulated by ADH; AQP4 brain). Osmotic pressure = πV = nRT (van't Hoff); plasma osmolality = 275-295 mOsm/kg (2[Na] + BUN/2.8 + glucose/18). Tonic fluids: isotonic (NS 0.9 %, RL), hypertonic (3 % saline, mannitol), hypotonic (0.45 % saline). Reverse osmosis used in water purification (WFI preparation).

✔ Correct — D: Na⁺-K⁺ ATPase — primary active transporter, hydrolyses 1 ATP to extrude 3 Na⁺ out + bring 2 K⁺ in (per cycle) against concentration gradients. Maintains intracellular [Na⁺] low (~ 12 mM) + [K⁺] high (~ 140 mM); extracellular opposite. Contributes to resting membrane potential (RMP ≈ -70 mV) + cell volume regulation. Electrogenic (net +1 out). Uses 20-40 % basal cellular ATP. α + β subunits; P-type ATPase family. Inhibitors: cardiac glycosides (digoxin, ouabain) → ↑ intracellular Ca²⁺ via NCX → positive inotropy. Bufadienolides (toad toxins) also inhibit.

✔ Correct — A: Endothelium — simple squamous epithelium lining blood vessels + lymphatics + heart chambers (endocardium). Mesodermal origin. Functions: selective permeability, anti-thrombotic surface (expresses thrombomodulin, tissue plasminogen activator, NO via eNOS, prostacyclin PGI₂), vasomotor tone regulation (NO + endothelin-1), leukocyte trafficking (P-selectin, E-selectin, ICAM-1, VCAM-1 during inflammation). Dysfunction underlies atherosclerosis, hypertension, diabetes vascular complications. Continuous, fenestrated (kidney glomerulus, endocrine), discontinuous / sinusoidal (liver, spleen, bone marrow).

✔ Correct — B: Dense regular connective tissue (tendons, ligaments, aponeuroses) — parallel arrays of type I collagen fibres resist uni-directional tensile force. Tendons connect muscle → bone; ligaments bone → bone. Collagen type I (bone + tendon), II (hyaline cartilage), III (reticular + early wound + vessels), IV (basement membrane), V (bone + placenta), VII (anchoring fibrils). Fibroblasts secrete procollagen → extracellular cleavage → tropocollagen → fibrils → fibres. Vitamin C required for prolyl + lysyl hydroxylation (scurvy defect). Hydroxyproline + hydroxylysine unique amino acids.

✔ Correct — C: Sarcomere — basic contractile unit of striated muscle, extending from one Z-disc to the next. Contains thick filaments (myosin II — A-band) + thin filaments (actin, troponin, tropomyosin — I-band). Resting length ~ 2.2 μm. Structures: Z-disc (α-actinin anchors thin filaments + titin); M-line (myomesin anchors thick filaments); H-zone (myosin only); bare zone; I-band (actin only); A-band (overlap + myosin). Sliding filament theory (Huxley + Hanson 1954): Ca²⁺ binds troponin C → tropomyosin shift → cross-bridge cycling (ATP + myosin head + actin). I-band + H-zone shorten on contraction; A-band + sarcomere length too. Dystrophin links sarcomere → sarcolemma (absent in Duchenne MD).

✔ Correct — D: Stratum corneum — outermost of 5 epidermal layers (keratinised stratified squamous). Layers deep → superficial: stratum basale (germinativum, mitotic, attaches to basement membrane), stratum spinosum (desmosomes + "prickle cells" + Langerhans APCs), stratum granulosum (keratohyalin granules, lamellar bodies), stratum lucidum (only thick skin — palms + soles), stratum corneum (flat anucleate corneocytes + lipid "mortar"). Turnover time 28-40 days (faster in psoriasis). Primary skin barrier ("brick + mortar" model). pH ~ 5.5 acid mantle. Key target for topical drug delivery + penetration enhancers (SC is rate-limiting).

✔ Correct — A: Melanocytes — neural-crest-derived dendritic cells in stratum basale; produce melanin (eumelanin — brown / black, pheomelanin — red / yellow) from tyrosine via tyrosinase (rate-limiting). Package melanin into melanosomes → transferred via dendrites to ~ 30-40 adjacent keratinocytes (epidermal melanin unit). Melanin absorbs UV + forms supranuclear cap protecting DNA. Stimulated by α-MSH (POMC-derived), UV exposure, MC1R activation. Disorders: albinism (tyrosinase or OCA2 defect), vitiligo (autoimmune destruction), melasma (chloasma, pregnancy + oestrogen), melanoma (malignancy). Other epidermal cells: keratinocytes (95 %), Langerhans (dendritic APC — skin immunity), Merkel (touch).

✔ Correct — B: Sebaceous glands — holocrine-type (entire cell disintegrates to release secretion) exocrine glands opening into hair follicles (pilosebaceous unit). Secrete sebum (triglycerides + wax esters + squalene + cholesterol) — lubrication + waterproofing + antimicrobial. Densest on face + scalp + upper chest + back. Absent on palms + soles. Androgen-stimulated (5α-DHT via 5α-reductase type 1); acne in puberty due to hypersecretion + follicular hyperkeratinisation + Cutibacterium acnes + inflammation. Modified sebaceous: Meibomian (eyelid — tear lipid layer), Fordyce spots (lips), areolar glands (Montgomery tubercles, nipple). Sweat glands: eccrine (thermoregulation, all body) + apocrine (axilla, pubic, mammary — scent).

✔ Correct — C: Anatomical position — standard reference stance for describing human body. Features: body upright, standing erect, feet parallel + pointing forward, head + eyes directed anteriorly, arms at sides, palms facing forward (supinated — thumbs laterally). Reference for directional terms: superior (cranial) / inferior (caudal); anterior (ventral) / posterior (dorsal); medial / lateral; proximal / distal; superficial / deep. Planes: sagittal (left-right — midsagittal = median), frontal / coronal (anterior-posterior), transverse / horizontal / axial. Body cavities: dorsal (cranial + vertebral) + ventral (thoracic — pleural + mediastinum + pericardial — + abdomino-pelvic). Supine = face up; prone = face down.

✔ Correct — D: Mid-sagittal (median) plane divides body into equal right + left halves. Sagittal planes are parallel to median; if off-centre they produce unequal halves (parasagittal). Frontal (coronal) plane — anterior (ventral) + posterior (dorsal) halves. Transverse (horizontal / axial) plane — superior (cranial) + inferior (caudal) halves. Oblique — combination of other planes. Related directional terms: medial (toward midline) / lateral (away); proximal (near trunk) / distal (far from trunk); superficial (near surface) / deep (internal); ipsilateral (same side) / contralateral (opposite side). Foundation for cross-sectional imaging: CT + MRI views.

✔ Correct — A: Homeostasis (Walter Cannon 1929; concept by Claude Bernard 19th c. "milieu intérieur") — maintenance of a relatively constant internal environment despite external fluctuations. Regulated variables: body temperature (37 °C via hypothalamus), blood pH (7.35-7.45), plasma glucose (70-110 mg/dL), Na⁺ (135-145 mEq/L), K⁺ (3.5-5.0), Ca²⁺ (8.5-10.5), osmolality (275-295 mOsm/kg), MAP (65-110 mmHg), body water (~ 60 %). Controlled by negative feedback loops — sensor (receptor) → control centre (hypothalamus / medulla) → effector (muscle / gland). Positive feedback rarer — childbirth oxytocin, LH surge, coagulation cascade. Disease states = homeostasis failure.

✔ Correct — B: Pericardial cavity — mediastinal cavity containing the heart. Surrounded by pericardium: fibrous pericardium (outer, tough CT, attaches to diaphragm + great vessels) + serous pericardium (parietal layer lines fibrous; visceral layer / epicardium on heart surface). Pericardial cavity between parietal + visceral serous layers contains ~ 20-50 mL serous fluid (lubrication). Disorders: pericarditis (pleuritic chest pain + friction rub), pericardial effusion, cardiac tamponade (Beck's triad: ↓BP, ↑JVP, muffled heart sounds), constrictive pericarditis (Kussmaul sign). Other ventral cavities: pleural (lungs), peritoneal (abdominal organs). Dorsal cavity: cranial (brain) + vertebral (spinal cord).

✔ Correct — C: Ribosomes — site of translation (mRNA → protein). Ribonucleoprotein particles; eukaryotic 80S = 60S (5S + 5.8S + 28S rRNA + 49 proteins) + 40S (18S rRNA + 33 proteins); prokaryotic + mitochondrial 70S = 50S + 30S. Found free (cytoplasmic proteins) + membrane-bound on rough ER (secretory + membrane proteins). Three tRNA sites: A (aminoacyl), P (peptidyl), E (exit). Initiation (40S + Met-tRNAi + mRNA + eIFs → 80S), elongation (EF-1α, EF-2), termination (release factor eRF at stop codon). Antibiotics target bacterial 70S: streptomycin (30S — misreading), tetracycline (30S — A-site block), chloramphenicol (50S — peptidyl transferase), erythromycin (50S — translocation), linezolid (50S — initiation).

✔ Correct — A: Smooth ER (SER) — lacks ribosomes; tubular + vesicular. Functions: lipid + steroid synthesis (cholesterol, steroid hormones in adrenals + gonads), phospholipid synthesis, drug + xenobiotic detoxification via cytochrome P450 enzymes (CYP1A2, CYP2D6, CYP3A4 etc.), glycogenolysis (glucose-6-phosphatase releases glucose), Ca²⁺ storage (especially sarcoplasmic reticulum in muscle — ryanodine + IP₃ receptors). Hepatocyte SER hypertrophy with chronic drug / ethanol exposure → enzyme induction + tolerance. Rough ER (RER) — ribosome-studded; translation + co-translational translocation + N-linked glycosylation + disulphide bonds + protein folding (BiP chaperone, PDI). Goblet cells + plasma cells + pancreatic acinar = RER-rich.

✔ Correct — D: Nucleolus — dense non-membrane-bound subdomain within the nucleus where rRNA is transcribed (by RNA polymerase I from nucleolar organiser regions — NORs on chromosomes 13, 14, 15, 21, 22) + processed (28S + 18S + 5.8S from 45S precursor) + assembled with ribosomal proteins (imported from cytoplasm) into 60S + 40S subunits, then exported to cytoplasm for final maturation. 5S rRNA transcribed separately by RNA pol III outside nucleolus + imported. Structure: fibrillar centre + dense fibrillar + granular components. Prominent in cells with high protein synthesis (hepatocytes, plasma cells, neurons, rapidly dividing cancer cells). Transcription: mRNA by RNA pol II, tRNA + 5S by pol III.

✔ Correct — B: Tight junctions (zonula occludens) — apical-most circumferential junctions that seal paracellular space + create a selective permeability barrier (regulate paracellular transport). Molecular components: claudins (form pore-size-selective strands), occludin, JAM (junction adhesion molecule), ZO-1 / ZO-2 / ZO-3 scaffold linking to actin. Also maintain apical-basolateral membrane polarity (fence function). Cell junctions (apical → basal): tight junction, zonula adherens (cadherin-actin), desmosome (macula adherens — desmoglein / desmocollin to intermediate filaments), hemidesmosome (integrin to laminin in BM), gap junction (connexons — 6 connexins — electrical + small molecule communication). Sites: blood-brain barrier, blood-testis barrier, intestinal + renal tubule epithelium.

✔ Correct — C: WBC differential (approximate, adults): Neutrophils 50-70 % (polymorph, multi-lobed nucleus; first responders in bacterial infection; phagocytic; myeloperoxidase + defensins; lifespan ~ 5-7 d; pus cell); Lymphocytes 20-40 % (T / B / NK); Monocytes 2-8 % (largest; macrophage + dendritic precursor); Eosinophils 1-4 % (bi-lobed, pink granules; parasites + allergy; IL-5 activation); Basophils < 1 % (violet granules — histamine + heparin; allergic reactions). Mnemonic: "Never Let Monkeys Eat Bananas" (%-order Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil). Absolute neutrophil count (ANC) = WBC × (%Neutro + %Bands) / 100; normal > 1 500; < 500 = severe neutropenia (chemotherapy, agranulocytosis from clozapine + methimazole + chloramphenicol).

✔ Correct — A: Cardiac muscle — striated + branched + uninucleated (single centrally placed nucleus) with unique intercalated discs at cell-cell junctions. Intercalated discs contain: fascia adherens (anchor actin — force transmission), desmosomes (anchor intermediate filaments — mechanical strength), gap junctions (connexin 43 — electrical coupling for syncytial contraction). Resting membrane potential ~ -90 mV; action potential ~ 300 ms (long plateau via L-type Ca²⁺ channels). SA node pacemaker → AV node → Bundle of His → Purkinje fibres. Cannot be tetanised (long refractory period). Involuntary (autonomic). Features: striated (like skeletal) + involuntary (like smooth) + intercalated discs + branched morphology + central nucleus.

✔ Correct — B: Adult human skeleton = 206 bones (neonate has ~ 270-300; bones fuse with age). Divided into: Axial skeleton (80 bones) = skull (22 — 8 cranial: frontal, 2 parietal, 2 temporal, occipital, sphenoid, ethmoid + 14 facial: 2 maxilla, 2 zygomatic, 2 nasal, 2 lacrimal, 2 palatine, 2 inferior nasal conchae, vomer, mandible) + 6 ossicles (3 per ear — malleus, incus, stapes — smallest bone) + hyoid + vertebral column 26 (7 cervical + 12 thoracic + 5 lumbar + sacrum [5 fused] + coccyx [3-5 fused]) + thorax 25 (sternum 1 + 12 pairs ribs = 24). Appendicular skeleton (126 bones) = pectoral girdle 4 (2 clavicles + 2 scapulae) + upper limbs 60 (30 × 2 — humerus + radius + ulna + 8 carpals + 5 metacarpals + 14 phalanges) + pelvic girdle 2 (2 hip / coxal = ilium + ischium + pubis fused) + lower limbs 60 (30 × 2 — femur + patella + tibia + fibula + 7 tarsals + 5 metatarsals + 14 phalanges). Femur = longest + strongest; stapes = smallest.

✔ Correct — A: Femur (thigh bone) = longest + strongest + heaviest bone in human body (~ 26.74 % of height, ~ 48 cm in average adult male). Superior end: head (articulates with acetabulum of hip — ball + socket synovial), neck (common fracture site in elderly osteoporosis), greater + lesser trochanters. Shaft has linea aspera (muscle attachment). Distal end: medial + lateral condyles articulate with tibia (knee = hinge synovial, largest joint). Adductor tubercle on medial epicondyle. Clinical: neck-of-femur fracture (intracapsular) risks avascular necrosis of head due to retinacular vessel disruption; hence need for hip replacement. Superlatives: Smallest = stapes (middle ear, ~ 3 mm). Longest = femur. Widest = pelvis. Hardest tissue = tooth enamel (Mohs ~ 5). Strongest (tensile) = femur diaphysis. Hyoid = only bone not articulating with another bone (floats in neck between mandible + larynx). Clavicle = 1st bone to ossify (fetal week 5) + most commonly fractured.

✔ Correct — C: Vertebral column = 33 vertebrae total (26 separate in adults): 7 cervical (C1-C7; neck; C1 Atlas — supports skull, no body, no spinous process; C2 Axis — has dens / odontoid process; C7 vertebra prominens with long spinous process). All cervical have foramen transversarium (carries vertebral artery through C1-C6; not C7). 12 thoracic (T1-T12; articulate with ribs via costal facets). 5 lumbar (L1-L5; largest bodies, no costal facets; L4 spinous process = iliac crest level = lumbar puncture site L3-L4 or L4-L5). 5 sacral (fused into sacrum; articulates with hip bones). 3-5 coccygeal (fused into coccyx; vestigial tail). Primary curves (kyphosis) = thoracic + sacral (convex posteriorly, retained from fetal). Secondary curves (lordosis) = cervical (develops head lifting ~ 3 mo) + lumbar (develops when walking ~ 12 mo). Scoliosis = lateral curvature. Intervertebral discs = fibrocartilage (annulus fibrosus + nucleus pulposus — remnant of notochord; disc prolapse most common at L4-L5 / L5-S1).

✔ Correct — D: 12 pairs of ribs: True ribs (vertebrosternal) = 7 pairs (1-7) — articulate directly with sternum via own costal cartilage. False ribs = 3 pairs (8-10) — vertebrochondral — cartilages fuse with cartilage of rib 7 → sternum. Floating ribs = 2 pairs (11-12) — vertebral only; anterior end free, no sternal attachment. Rib 1 = shortest + broadest + most curved; has scalene tubercle + groove for subclavian artery. Typical rib has head (2 articular facets, articulates with vertebral bodies of same + superior vertebra), neck, tubercle (articulates with transverse process), shaft + costal groove (on inferior border — contains intercostal vein + artery + nerve, VAN from top down). Sternum = manubrium + body + xiphoid process; sternal angle (angle of Louis) at T4-T5 = rib 2 attachment, bifurcation of trachea, start + end of aortic arch, superior border of pericardium, T4 level. Thoracic cage = 24 ribs + 1 sternum + 12 thoracic vertebrae = 37 bones.

✔ Correct — C: Osteoclast = multinucleated (5-50 nuclei) giant cell derived from monocyte-macrophage haematopoietic lineage (HSC → CMP → monocyte → osteoclast precursor); differentiation driven by M-CSF (RANK expression) + RANKL (from osteoblasts / stromal cells / osteocytes — binds RANK → NFκB / NFATc1 → fusion + activation); inhibited by osteoprotegerin (OPG, decoy RANKL receptor). Resorb bone via ruffled border + sealing zone — secrete H+ (via V-ATPase proton pump + Cl-/HCO3- exchanger) to dissolve hydroxyapatite → cathepsin K + MMP-9 + TRAP digest collagen matrix. Creates Howship's lacunae. Anti-resorptives block osteoclasts: bisphosphonates (alendronate, risedronate, zoledronate — inhibit farnesyl pyrophosphate synthase → apoptosis), denosumab (RANKL mAb), calcitonin, oestrogen (↓ RANKL). Osteoblasts (bone forming) + osteocytes (mature, mechanosensory — produce sclerostin → Wnt inhibition) + bone-lining cells (quiescent osteoblasts) derive from MSC. Chondroblasts / chondrocytes from MSC too.

✔ Correct — B: Bone matrix = organic (35 %) "osteoid" — ~ 90 % Type I collagen (provides tensile strength) + 10 % ground substance / non-collagenous proteins (osteocalcin, osteopontin, osteonectin, bone sialoprotein, proteoglycans) + growth factors (TGF-β, BMPs, IGF). Inorganic (65 %) — hydroxyapatite crystals Ca₁₀(PO₄)₆(OH)₂ deposited on collagen fibrils (provides compressive strength + rigidity). Also Mg, Na, K, carbonate, F-. Collagen types high-yield: Type I = bone + skin + tendon + dentin + cornea ("bone + bOne"); Type II = hyaline + elastic cartilage + vitreous humor ("carTWOlage"); Type III = reticular fibres (liver, spleen, bone marrow, early wound, granulation tissue); Type IV = basement membrane (with laminin, "floor / foundation"); Type V = placenta; Type VII = anchoring fibrils in epidermal basement membrane. Osteogenesis imperfecta (brittle bones) = Type I collagen mutation (COL1A1/COL1A2). Ehlers-Danlos syndrome = multiple collagen defects. Alport syndrome = Type IV defect.

✔ Correct — A: Intramembranous ossification — bone forms directly from mesenchymal condensation without a cartilage template. Forms flat bones of skull (frontal, parietal, occipital squamous, temporal squamous), facial bones, medial clavicle + mandible. Steps: mesenchyme condenses → MSC differentiates into osteoblast → secretes osteoid → mineralisation → osteocyte entrapment → trabecular woven bone → remodelling to lamellar. Endochondral ossification — majority of bones (long bones, vertebrae, ribs, pelvis, base of skull) — cartilage model first, then replaced by bone. Steps: mesenchyme → chondroblasts → hyaline cartilage template → perichondrium / periosteum forms → primary ossification centre at diaphysis (via nutrient artery, ~ week 8-12 fetal) → secondary ossification centres at epiphyses (after birth, most by age 5) → epiphyseal (growth) plate persists between metaphysis + epiphysis → longitudinal growth continues until plate closes (puberty, driven by oestrogen). Epiphyseal plate closure: earlier in females; complete by ~ 18 F / 21 M. Achondroplasia = FGFR3 gain-of-function → ↓ endochondral growth → disproportionate dwarfism (short limbs, normal trunk).

✔ Correct — C: Haversian system (osteon) = structural + functional unit of compact / cortical bone. Each osteon = central (Haversian) canal containing neurovascular bundle (artery + vein + nerve + lymphatic) surrounded by concentric lamellae (3-8 rings). Lacunae (within lamellae) house osteocytes; lacunae interconnected by canaliculi (microchannels allowing gap-junction-mediated nutrient exchange between osteocytes + central canal). Volkmann's (perforating) canals = transverse canals connecting Haversian canals with periosteum + endosteum, carrying vessels. Between osteons: interstitial lamellae (remnants of older osteons). Outer / inner circumferential lamellae surround cortical shell. Spongy / trabecular / cancellous bone = no osteons; has trabeculae (lattice of spicules) with red marrow in spaces — arranged along lines of stress (Wolff's law — bone adapts to load). Cortical = 80 % of skeletal mass; trabecular = 20 % but 80 % of surface area (higher turnover). Nutrient artery supplies diaphysis. Periosteum (outer dense fibrous + inner cellular / osteogenic) + endosteum line inner surfaces. Sharpey's fibres anchor periosteum.

✔ Correct — B: Calcitonin (from parafollicular C cells of thyroid; 32 aa peptide) — secreted when Ca²⁺ is high; lowers plasma Ca²⁺ by (1) inhibiting osteoclast activity + number ("tones down" bone resorption), (2) ↑ renal Ca²⁺ + PO4³⁻ excretion. Minor role in adult Ca²⁺ homeostasis (fetal / paediatric more important); salmon calcitonin used in Paget disease + hypercalcaemia + osteoporosis (nasal spray). Calcium homeostasis (normal serum 8.5-10.5 mg/dL, ionised 4.5-5.5 mg/dL; ~ 40 % albumin-bound, 10 % complexed, 50 % free / active): PTH (chief cells of parathyroid, 84 aa, ↑ Ca²⁺ / ↓ PO4³⁻) acts via: (1) bone — ↑ osteoclast via RANKL (released from osteoblast), (2) kidney — ↑ Ca²⁺ reabsorption (DCT) + ↓ PO4³⁻ reabsorption (PCT) + ↑ 1α-hydroxylase activation, (3) gut indirectly via calcitriol. Calcitriol / 1,25(OH)₂D₃ (active vitamin D) — ↑ gut Ca²⁺ + PO4³⁻ absorption (via calbindin-D + TRPV6), ↑ bone remodelling. Deficiency: children = rickets; adults = osteomalacia. Hyperparathyroidism → osteitis fibrosa cystica ("brown tumours"), kidney stones, psychosis — "bones + stones + moans + groans".

✔ Correct — D: Functional classification: Synarthrosis = immovable (skull sutures, gomphosis tooth-socket); Amphiarthrosis = slightly movable (pubic symphysis, intervertebral disc, inferior tibiofibular); Diarthrosis = freely movable (all synovial joints — shoulder, hip, knee, elbow, wrist). Structural classification: (1) Fibrous — sutures (skull, synarthrosis), syndesmosis (radioulnar, tibiofibular — amphiarthrosis), gomphosis (teeth peg-in-socket, synarthrosis); (2) Cartilaginous — synchondrosis (hyaline, e.g., epiphyseal plate, costochondral joint — synarthrosis), symphysis (fibrocartilage, e.g., intervertebral disc, pubic symphysis, manubriosternal — amphiarthrosis); (3) Synovial — diarthrosis, 6 subtypes: (a) Hinge (uniaxial — elbow, knee, ankle, interphalangeal); (b) Pivot (uniaxial rotation — atlantoaxial C1-C2, proximal radioulnar); (c) Ball + socket (multi-axial — shoulder, hip); (d) Condyloid / ellipsoidal (biaxial — wrist radiocarpal, MCP 2-5, atlanto-occipital); (e) Saddle (biaxial — 1st carpometacarpal thumb, sternoclavicular); (f) Gliding / plane (non-axial — intercarpal, intertarsal, acromioclavicular, zygapophyseal / facet).

✔ Correct — A: Hip joint = ball + socket (multi-axial, 3 degrees of freedom — flexion/extension, abduction/adduction, rotation/circumduction). Head of femur (ball) fits into acetabulum (socket, deepened by acetabular labrum — fibrocartilage). Strongest ligaments = iliofemoral (Y ligament of Bigelow, strongest in body), pubofemoral, ischiofemoral + ligamentum teres (artery to head of femur — minor in adults). Most stable ball+socket (deep socket) — hip dislocation requires severe trauma; shoulder (glenohumeral) is most mobile but least stable (shallow glenoid, relies on rotator cuff: Supraspinatus, Infraspinatus, Teres minor, Subscapularis — SITS; supraspinatus tear most common). Synovial joint structure: articular cartilage (hyaline) covers bone ends — avascular, aneural, relies on synovial fluid for nutrition; joint cavity filled with synovial fluid (hyaluronic acid-rich, from synovial membrane Type A macrophage + Type B fibroblast-like cells; lubricin, proteinase inhibitors); fibrous capsule + synovial membrane; ligaments (intra- / extracapsular); menisci (e.g., knee medial + lateral C-shaped fibrocartilage; ACL most commonly torn); bursae (fluid sacs reducing friction). Joint examples: Elbow / knee / ankle / interphalangeal = hinge; Atlanto-axial (C1-C2) / proximal radioulnar = pivot; Wrist / MCP / atlanto-occipital = condyloid; Thumb CMC = saddle; Intercarpal = gliding.

✔ Correct — B: Synovial fluid = viscous dialysate of plasma + hyaluronic acid + lubricin (proteoglycan 4) + proteinase inhibitors produced by Type B synoviocytes (fibroblast-like cells) of synovial membrane. Type A synoviocytes = macrophage-like (phagocytic, remove debris). Normal volume small (~ 1-4 mL in knee). Functions: (1) lubrication (boundary + fluid-film), (2) nutrition of avascular articular cartilage (diffusion + cyclic loading / weeping lubrication), (3) shock absorption, (4) waste removal, (5) immune surveillance. Crystal arthritis: gout (monosodium urate crystals — needle-shaped, negatively birefringent — yellow parallel to axis; treatment: NSAID, colchicine, allopurinol, febuxostat, pegloticase); pseudogout / CPPD (calcium pyrophosphate — rhomboid, positively birefringent — blue parallel). Rheumatoid arthritis = autoimmune synovitis → pannus → cartilage + bone erosion (anti-CCP, RF positive, morning stiffness > 1 h, symmetrical small joints). Osteoarthritis = wear + tear degeneration (asymmetrical, large weight-bearing joints, Heberden + Bouchard nodes, osteophytes, joint-space narrowing, subchondral sclerosis + cysts).

✔ Correct — C: Sarcomere = functional / contractile unit of striated muscle, extending from one Z-line (Z-disc) to the next. Bands visible under microscope: A-band (dark, Anisotropic, full length of thick filaments — myosin; stays constant during contraction; contains thin filaments overlap). I-band (light, Isotropic, only thin filaments — actin; spans across Z-line; shortens during contraction). H-zone (central A-band region with thick filaments only, no overlap; shortens during contraction). M-line (centre of H-zone, holds thick filaments). Z-line (anchors thin filaments; α-actinin). Mnemonic: "HIZ AM" — H + I + Z shorten; A + M stay same. Sliding filament theory (Huxley + Hanson 1954): thin + thick filaments slide past each other; sarcomere + I-band + H-zone shorten; A-band + filament lengths unchanged. Hierarchy: Muscle → fasciculus (bundle of fibres, surrounded by perimysium) → muscle fibre / cell (surrounded by endomysium, multinucleate) → myofibril → sarcomere → myofilaments (thick myosin + thin actin / tropomyosin / troponin). Triad = T-tubule + 2 flanking terminal cisternae of SR (at A-I junction in skeletal; dyad at Z-line in cardiac).

✔ Correct — A: Skeletal muscle contraction — Ca²⁺ binds troponin C (TnC) → conformational change → troponin I (TnI) releases from actin → tropomyosin shifts away from myosin-binding sites on actin → cross-bridge cycle begins. Sliding-filament cross-bridge cycle: (1) ATP binding to myosin head → detachment from actin; (2) ATP hydrolysis → myosin head cocked (high-energy state ADP + Pi bound); (3) Ca²⁺ exposes actin site → myosin binds forming cross-bridge; (4) power stroke — Pi released, then ADP released, myosin head pivots pulling actin toward M-line (~ 10 nm displacement); (5) new ATP binds → detachment. Rigor mortis = no ATP → myosin stuck on actin. Troponin complex (on thin filament every 40 nm): TnT (tropomyosin-binding), TnI (inhibitory, binds actin), TnC (Ca²⁺-binding; cardiac isoform is clinical biomarker TnI + TnT for MI — rise ~ 3-6 h, peak 24 h, normal ~ 7-10 d). Tropomyosin = α-helical rod blocking myosin-binding sites at rest. Smooth muscle: no troponin — Ca²⁺ binds calmodulin → activates myosin light-chain kinase (MLCK) → phosphorylates myosin regulatory light chain → contraction. EC coupling: AP → T-tubule → DHPR (L-type Ca²⁺ channel) mechanically couples to RyR1 (SR Ca²⁺ release channel in skeletal) or triggers CICR via RyR2 in cardiac.

✔ Correct — B: Acetylcholine (ACh) = sole neurotransmitter at the neuromuscular junction (NMJ); binds nicotinic ACh receptor (N_M, muscle type, pentameric (α2βγδ fetal / α2βεδ adult) ligand-gated cation channel) on motor end plate → Na+ influx → end-plate potential → AP → contraction. Steps: AP arrives at motor nerve terminal → opens voltage-gated Ca²⁺ channel (P/Q-type) → ACh-containing vesicles fuse + release ACh (quantal release, SNARE proteins — syntaxin, SNAP-25, synaptobrevin); ACh binds nAChR → Na+ / K+ channel opens → end-plate depolarisation → spreads via T-tubules → DHPR → RyR1 → Ca²⁺ release from SR. ACh cleared by acetylcholinesterase (AChE) in synaptic cleft → choline + acetate. NMJ pharmacology: Non-depolarising blockers (tubocurarine, atracurium, vecuronium, rocuronium, pancuronium) = competitive nAChR antagonists, reversed by neostigmine + glycopyrrolate. Depolarising blocker = succinylcholine (agonist → sustained depolarisation → desensitisation; reversal: wait / cholinesterase inhibitors); risks malignant hyperthermia + hyperkalaemia. Botulinum toxin = blocks ACh release (SNAP-25 cleavage). Myasthenia gravis = autoantibodies against nAChR → fatigable muscle weakness; tx pyridostigmine + immunosuppressives + thymectomy. Lambert-Eaton myasthenic syndrome = antibodies to VGCC (paraneoplastic small cell lung cancer). Curare = historical South American arrow poison.

✔ Correct — C: Skeletal muscle Ca²⁺ release = from sarcoplasmic reticulum (SR) via ryanodine receptor (RyR1) on terminal cisternae — activated by mechanical coupling with voltage-sensor dihydropyridine receptor (DHPR, L-type Ca²⁺ channel) on T-tubule (depolarisation-induced Ca²⁺ release, does NOT require extracellular Ca²⁺). Resting [Ca²⁺]cytosol ~ 100 nM; rises to ~ 1-10 μM during contraction. Ca²⁺ is pumped back into SR by SERCA (Sarco-Endoplasmic Reticulum Ca²⁺ ATPase, inhibited by thapsigargin) → muscle relaxation. Ca²⁺ stored in SR bound to calsequestrin (high capacity, low affinity). Cardiac muscle EC coupling — different: extracellular Ca²⁺ entry via DHPR (L-type) triggers Ca²⁺-induced Ca²⁺ release (CICR) from SR via RyR2 → amplifies signal. Smooth muscle — depolarisation via VGCC → Ca²⁺ entry + release from SR via IP3R (triggered by Gq-PLC-IP3 pathway — α1, M3, H1 receptors). RyR isoforms: RyR1 skeletal, RyR2 cardiac, RyR3 brain. Mutations: Malignant hyperthermia (RyR1 gain-of-function → caffeine + halothane + succinylcholine triggers massive Ca²⁺ release → hyperthermia + rhabdomyolysis; tx dantrolene inhibits RyR1); Central core disease; CPVT (RyR2 → catecholaminergic polymorphic VT).

✔ Correct — A: Skeletal muscle fibre types: Type I (slow oxidative, "slow-twitch") — red, high myoglobin + mitochondria + capillary density, oxidative metabolism, fatigue-resistant, low force, sustained activity (postural muscles, soleus, marathon runners); small motor units; innervated by small motor neurons. Type IIa (fast oxidative-glycolytic) — red / pink, moderate mitochondria, both oxidative + glycolytic, fatigue-intermediate (middle-distance, swimmers). Type IIb / IIx (fast glycolytic, "fast-twitch") — white, low mitochondria + myoglobin, anaerobic glycolysis, high force, fast but quickly fatigued (sprinters, weightlifters); large motor units; innervated by large motor neurons. Trained athletes show fibre-type + enzymatic adaptation. Motor unit = 1 motor neuron + all muscle fibres it innervates. Innervation ratio: small in precision muscles (extraocular 3-10 : 1, lumbricals 100 : 1) vs large in powerful (gastrocnemius 1000 : 1, gluteus maximus 2000 : 1). Size principle (Henneman) = small motor units recruited first (fatigue-resistant Type I), then larger (Type IIa → IIb) as force demand increases. ATP sources during contraction (in order): (1) phosphocreatine / creatine kinase — first ~ 10 s; (2) anaerobic glycolysis — ~ 1-2 min (produces lactate → burning sensation); (3) oxidative phosphorylation — sustained activity.

✔ Correct — D: Rigor mortis (Latin "stiffness of death") — ATP is required for myosin to detach from actin (step 1 of cross-bridge cycle). After death, ATP production ceases; residual ATP depleted; myosin heads remain locked on actin → muscle stiffens. Additionally, SR fails to reaccumulate Ca²⁺ → cytosolic Ca²⁺ stays high → cross-bridges maintain. Onset: ~ 2-6 h post-mortem; full rigor: ~ 12 h; resolves: ~ 24-48 h (due to autolytic degradation of contractile proteins + lysosomal enzymes). Sequence: begins in smaller muscles (face, eyelids, jaw, fingers) → progresses to larger. Factors accelerating rigor: high temperature, vigorous exertion before death, fever. Forensic relevance = time of death estimation (along with livor mortis, algor mortis, putrefaction, stomach contents). Cadaveric spasm = instantaneous rigor (rare, immediate onset in strenuous activity at moment of death — grip on weapon / clothing). Muscle cramps (in life) = sustained involuntary contraction — often from electrolyte imbalance (Mg²⁺, Ca²⁺, K+), dehydration, overexertion — not true rigor.

✔ Correct — B: Phosphocreatine (PCr / creatine phosphate) system via creatine kinase (CK): PCr + ADP ⇌ Creatine + ATP (reversible, very rapid). Stored ~ 4× more than ATP in muscle (20-25 mM vs 5-8 mM ATP). Provides explosive power for ~ 5-10 seconds (sprint start, weightlifting first rep, jumping). Then anaerobic glycolysis (~ 10-120 seconds) generates 2 net ATP / glucose + lactate (via LDH); contributes to EPOC (excess post-exercise O₂ consumption) / oxygen debt. Beyond 2 minutes, aerobic oxidative phosphorylation dominates — ~ 30-32 ATP per glucose (or FA oxidation via β-oxidation during endurance). Creatine = synthesised in liver + kidney + pancreas from glycine + arginine + SAM (methionine); transported to muscle; converted to creatinine (non-enzymatic) at ~ 2 % / day → excreted by kidney (creatinine clearance = GFR marker). Creatine supplementation — 5 g / day — ↑ PCr stores; ergogenic for short bursts. CK isoforms (dimers of M + B subunits): CK-MM = skeletal muscle; CK-MB = cardiac (clinical MI marker pre-troponin era, rises 4-6 h, peak 24 h); CK-BB = brain + smooth. Lohmann reaction = CK-catalysed PCr ↔ ATP.

✔ Correct — A: Isotonic contraction (iso = same, tonic = tension) — tension remains constant; muscle length changes — concentric (shortens, e.g., lifting barbell up — biceps flexion) or eccentric (lengthens under load, e.g., lowering barbell — biceps controlled extension; causes more DOMS / delayed-onset muscle soreness). Isometric contraction — length constant, tension changes (e.g., pushing against immovable wall, holding a plank, grip dynamometer). Isokinetic contraction — constant velocity (requires special equipment). Muscle twitch = response to single stimulus: latent period (~ 2 ms) → contraction phase (~ 10-100 ms) → relaxation phase (~ 10-100 ms). Summation = rapid sequential stimuli → greater tension (temporal summation). Tetanus = rapid stimuli (60-100 Hz) → sustained maximal contraction, no relaxation between twitches (unfused → incomplete tetanus → fused / complete tetanus). Cardiac muscle CANNOT tetanize (long absolute refractory period ~ 250 ms vs ~ 2 ms for skeletal). Length-tension relationship: optimal sarcomere length ~ 2.0-2.2 μm → maximal overlap between thick + thin filaments → maximum force. Force-velocity relationship: inverse — higher load → slower velocity. Muscle spindle (intrafusal fibres) = stretch receptor → monosynaptic stretch reflex (patellar tendon → quadriceps). Golgi tendon organ (GTO) = tension monitor in tendon → inverse stretch reflex (autogenic inhibition).

✔ Correct — C: Neuron = structural + functional excitable unit; ~ 86 billion in human brain. Parts: (1) Soma / perikaryon (cell body with nucleus, Nissl bodies = rough ER). (2) Dendrites (input, multiple, tapered, contain Nissl). (3) Axon (output, single, from axon hillock — trigger zone / spike initiation; no Nissl; may be myelinated; ends as synaptic terminals / boutons). (4) Axon terminal / bouton (NT-containing vesicles). Classification by structure: multipolar (most CNS motor + interneurons — 1 axon + multiple dendrites), bipolar (retina, olfactory, inner ear hair cells — 1 axon + 1 dendrite), pseudounipolar (dorsal root ganglia sensory — T-shaped from single process), unipolar (invertebrates + some embryonic). By function: sensory / afferent (→ CNS); motor / efferent (CNS → effector); interneuron (within CNS, > 99 % of neurons). Neuroglia (support): CNS — astrocytes (BBB, K+ buffering, glutamate clearance, scar / gliosis; GFAP marker), oligodendrocytes (CNS myelin — 1 cell myelinates several axons), microglia (CNS macrophages from yolk sac / mesoderm — immune surveillance, phagocytosis), ependymal (line ventricles + central canal, produce + circulate CSF). PNS — Schwann cells (PNS myelin — 1 cell 1 internode; involved in regeneration via Büngner bands; stain with S100), satellite cells (surround sensory + autonomic ganglia neurons).

✔ Correct — A: Primary motor cortex (M1) = precentral gyrus of frontal lobe (Brodmann area 4) — contains upper motor neurons / Betz cells (layer V) whose axons descend via corticospinal + corticobulbar tracts. Motor homunculus = somatotopic mapping (lateral → medial = face / tongue → hand → trunk → foot/perineum on medial surface). Cerebral lobes + functions: Frontal — primary motor (precentral gyrus area 4), premotor (area 6), supplementary motor, Broca's area (inferior frontal gyrus area 44/45, LEFT dominant — motor speech; Broca's aphasia = expressive / non-fluent), prefrontal cortex (executive function, personality, working memory), frontal eye field (voluntary eye movements area 8). Parietal — primary somatosensory (postcentral gyrus areas 3, 1, 2), sensory homunculus, spatial awareness, taste (area 43). Right parietal lesion → hemi-neglect; Gerstmann syndrome (left parietal — acalculia + agraphia + finger agnosia + L/R disorientation). Occipital — primary visual cortex (area 17 / V1 around calcarine sulcus), visual association (areas 18, 19 / V2-V5). Temporal — primary auditory (superior temporal gyrus, areas 41-42, Heschl's gyri), Wernicke's area (posterior superior temporal / area 22 LEFT dominant — receptive language; Wernicke's aphasia = fluent but nonsensical), hippocampus / amygdala (memory + emotion — medial temporal, limbic). Insula — taste, interoception, visceral sensation. Limbic lobe — emotion + memory. Brodmann divided cortex into 52 cytoarchitectonic areas (1909).

✔ Correct — B: Cerebellum ("little brain", in posterior cranial fossa under tentorium) — coordinates voluntary movement (smoothness + accuracy + timing), balance, posture, muscle tone + motor learning. Has 3 lobes: anterior (spinocerebellum — trunk + limb control, gait), posterior (cerebrocerebellum — planning + timing + cognition), flocculonodular (vestibulocerebellum — balance + eye movement). Three peduncles: superior (to midbrain — efferent to red nucleus / thalamus), middle (from pons — input from cerebral cortex), inferior (from medulla — input from spinal cord + vestibular + olive). Cortex: molecular + Purkinje + granular layers; Purkinje cells (GABAergic) = only output neurons to deep nuclei. Deep nuclei (lateral → medial, mnemonic DEGF): Dentate, Emboliform, Globose, Fastigial. Signs of cerebellar lesion (ipsilateral): ataxia (gait + limb), dysmetria (past-pointing), dysdiadochokinesia (impaired rapid alternating movement), intention tremor (worsens with movement), hypotonia, scanning dysarthria, nystagmus, rebound phenomenon. Basal ganglia (caudate + putamen + globus pallidus + subthalamic nucleus + substantia nigra) — movement initiation + modulation (direct + indirect pathways); lesions cause Parkinson (hypokinetic, SN pars compacta dopamine loss), Huntington (hyperkinetic, caudate atrophy, CAG repeat on HTT ch 4), Hemiballismus (subthalamic), Wilson (copper).

✔ Correct — C: Medulla oblongata (lowest brainstem, continuous with spinal cord) — houses vital autonomic centres: (1) Cardiovascular centre — cardiac (vagal → ↓ HR / sympathetic → ↑ HR + contractility) + vasomotor (vasoconstrictor / vasodilator). (2) Respiratory centre — dorsal respiratory group (DRG, inspiration — drives phrenic + intercostal motor neurons) + ventral respiratory group (VRG, forceful expiration + inspiration) + pre-Bötzinger complex (rhythm pacemaker). Pons has pneumotaxic (cuts off inspiration → ↓ depth + ↑ rate) + apneustic (prolongs inspiration). (3) Deglutition (swallowing) centre. (4) Vomiting centre (area postrema on floor of 4th ventricle — CTZ / chemoreceptor trigger zone, outside BBB — senses toxins + emetics; receptors: D2, 5-HT3, H1, M1, NK1 → antiemetic targets). (5) Cough reflex. (6) Sneeze. (7) Hiccup. Origin of cranial nerves IX, X, XI, XII from medulla. Pyramidal decussation (corticospinal crossover ~ 85 %) occurs at lower medulla. Olives visible laterally (inferior olivary nucleus — cerebellar afferent via climbing fibres). Damage to medulla = often fatal. Brainstem summary: Midbrain (superior + inferior colliculi — visual + auditory reflexes; red nucleus; substantia nigra; CN III, IV origin; cerebral aqueduct). Pons (CN V, VI, VII, VIII origin; pontine nuclei relay to cerebellum; respiratory regulation). Medulla (CN IX, X, XI, XII; vital centres).

✔ Correct — A: Hypothalamus (diencephalon, below thalamus, forms floor of 3rd ventricle; ~ 4 g) = supreme homeostatic regulator + neuroendocrine link. Functions (mnemonic HEAL TAN): Hormones (hypothalamic-pituitary axis), Eating + Autonomic, Libido, Thermoregulation, Adrenergic-like stress, Neurosecretion. Major nuclei + hormones: Supraoptic + paraventricular — produce ADH (vasopressin) + oxytocin → stored + released from posterior pituitary. Arcuate — produces GHRH, GnRH, dopamine (= PIF / prolactin inhibitor), NPY / AgRP (orexigenic) + POMC (anorexigenic). Paraventricular — CRH, TRH. Anterior / preoptic — heat dissipation (vasodilation + sweating); damage → hyperthermia. Posterior — heat conservation (vasoconstriction + shivering); damage → poikilothermy. Lateral — hunger ("feeding centre" — orexin / hypocretin; lesion → anorexia + wasting). Ventromedial — satiety ("satiety centre"; lesion → hyperphagia + obesity + savage behaviour). Suprachiasmatic — master circadian pacemaker (via melanopsin retinal ganglion cells; entrained by light). Mammillary bodies — memory (Korsakoff / Wernicke — thiamine deficiency). Hypothalamic-pituitary portal system — hypophyseal portal veins carry releasing / inhibitory hormones (TRH, CRH, GnRH, GHRH, somatostatin, dopamine) to anterior pituitary; posterior pituitary receives neuronal axons directly from SON + PVN. Hormones released by anterior pituitary: ACTH, TSH, FSH, LH, GH, PRL (mnemonic "FLAT PiG"); posterior: ADH + oxytocin.

✔ Correct — B: Adult spinal cord ends as the conus medullaris at L1-L2 vertebral level (in neonates at L3 — due to differential growth between cord + vertebral column). Below conus, lumbosacral nerve roots form the cauda equina ("horse's tail") within the subarachnoid space. Filum terminale = pial extension from conus → coccyx (anchors cord). Spinal cord length ~ 45 cm (males), ~ 43 cm (females); has 2 enlargements — cervical (C4-T1 for brachial plexus) + lumbosacral (T11-L1 for lumbar + sacral plexus). Meninges (outer → inner): dura mater (tough; in spine = single layer, in skull = 2 layers); arachnoid (cobweb-like, avascular; subarachnoid space contains CSF + vessels); pia mater (delicate, vascular, adherent to cord / brain). Spaces: epidural (between vertebral periosteum + dura — fat + venous plexus — used for epidural anaesthesia); subdural (potential space); subarachnoid (CSF-filled — lumbar puncture into lumbar cistern at L3-L4 or L4-L5, below conus, safe). 31 pairs of spinal nerves: 8 cervical (C1-C8, first exits above C1 vertebra) + 12 thoracic + 5 lumbar + 5 sacral + 1 coccygeal. Each has ventral (motor efferent, anterior horn) + dorsal (sensory afferent, with ganglion) root joining to form mixed spinal nerve, which divides into dorsal + ventral rami. Dermatome = sensory area from 1 spinal level (landmarks: C7 middle finger, T4 nipple, T10 umbilicus, L1 inguinal, L4 medial malleolus, S1 little toe, S5 perianal).

✔ Correct — A: 12 pairs of cranial nerves. Mnemonic "On Old Olympus Towering Top A Finn And German Viewed Some Hops". Type mnemonic "Some Say Marry Money But My Brother Says Big Brains Matter More" (S = sensory, M = motor, B = both): CN I Olfactory (S — smell, only PNS nerve to CNS; bypass thalamus). CN II Optic (S — vision; actually CNS tract). CN III Oculomotor (M + parasympathetic — SR + IR + MR + IO + LPS; pupillary constriction via Edinger-Westphal). CN IV Trochlear (M — superior oblique, only nerve from DORSAL brainstem, longest intracranial course, only crossed CN). CN V Trigeminal (B — V1 ophthalmic + V2 maxillary + V3 mandibular; sensation to face + muscles of mastication; largest CN). CN VI Abducens (M — lateral rectus; longest intracranial course vulnerable in ↑ ICP → false localising sign). CN VII Facial (B — facial expression + stapedius + taste anterior 2/3 tongue via chorda tympani + parasympathetic to lacrimal + sublingual + submandibular). Bell's palsy = LMN VII paralysis. CN VIII Vestibulocochlear (S — hearing + balance). CN IX Glossopharyngeal (B — stylopharyngeus + taste posterior 1/3 + parotid parasympathetic + carotid sinus). CN X Vagus (B — longest, parasympathetic to thoracic + abdominal viscera to splenic flexure; palate + pharynx + larynx; recurrent laryngeal). CN XI Accessory (M — SCM + trapezius). CN XII Hypoglossal (M — tongue muscles except palatoglossus).

✔ Correct — D: CN X Vagus nerve (Latin "wanderer") = longest CN, carries ~ 75 % of all parasympathetic fibres. Origin: medulla (from nucleus ambiguus, dorsal motor nucleus of vagus, nucleus of solitary tract). Exits jugular foramen (along with IX + XI). Travels through neck (in carotid sheath between IA + IJV), thorax, enters abdomen via oesophageal hiatus at T10. Parasympathetic supply: pharynx, larynx (recurrent laryngeal), heart (SA + AV node → ↓ HR), lungs (bronchoconstriction, mucus), oesophagus, stomach, liver, pancreas, small + large intestine up to splenic flexure (left 1/3 transverse + descending + sigmoid colon + rectum get parasympathetic from S2-S4 pelvic splanchnics). Sensory: taste from epiglottis, sensation from external ear + larynx (internal laryngeal), aortic arch baroreceptors + chemoreceptors. Motor: most palatal + pharyngeal + all laryngeal muscles (except stylopharyngeus — IX + tensor veli palatini — V3). Recurrent laryngeal branches: right loops under subclavian; left loops under aortic arch (vulnerable in thyroid surgery, aortic aneurysm, mitral stenosis → hoarseness). Injury: uvula deviates AWAY from lesion side; palatal droop on affected side; loss of gag reflex (afferent IX, efferent X). Vagovagal reflex = stretch of stomach → ↑ secretion. Carotid sinus massage → baroreceptor stimulation → ↑ vagal tone → ↓ HR (SVT termination). Vagotomy — historical ulcer surgery. Vagal nerve stimulation (VNS) — FDA-approved for epilepsy + depression + recently for inflammation.

✔ Correct — A: Autonomic nervous system (ANS) = 2 divisions: Sympathetic (thoracolumbar, "fight or flight") — preganglionic neurons in intermediolateral cell column T1-L2 (short preganglionic fibres using ACh on nicotinic ganglionic receptors; long postganglionic fibres using noradrenaline on α + β adrenergic receptors). Exception: sweat glands + some blood vessels = postganglionic cholinergic sympathetic (muscarinic M3). Adrenal medulla = modified sympathetic ganglion (chromaffin cells) — releases 80 % adrenaline + 20 % noradrenaline directly into blood (single preganglionic fibre only). Sympathetic chain / paravertebral ganglia (3 cervical — SCG + MCG + stellate — + 11 thoracic + 4 lumbar + 4-5 sacral). Prevertebral ganglia (coeliac, superior + inferior mesenteric). Parasympathetic (craniosacral, "rest + digest") — preganglionic from CN III (Edinger-Westphal → pupil + ciliary), VII (superior salivatory → lacrimal + submandibular + sublingual), IX (inferior salivatory → parotid), X (dorsal motor nucleus → thoracoabdominal viscera to splenic flexure) + S2-S4 pelvic splanchnics (distal 1/3 colon + rectum + bladder + genitalia). Long preganglionic (ACh on nicotinic N_N) + short postganglionic (ACh on muscarinic M1-M5). Effects: eye (miosis + accommodation), lacrimation, salivation (watery), bronchoconstriction, ↓ HR, ↑ GI motility + secretion, ↑ bladder detrusor + relax sphincter, erection (point) + ejaculation (shoot — sympathetic). Enteric NS ("2nd brain") — intrinsic gut plexuses (submucosal Meissner + myenteric Auerbach). Key receptors: α1 (vasoconstriction, mydriasis, GU sphincter), α2 (presynaptic NT release inhibition, vasoconstriction, platelet aggregation), β1 (↑ HR + contractility + renin), β2 (bronchodilation + vasodilation in skeletal + glycogenolysis), β3 (lipolysis, bladder relaxation), M1 (CNS + gastric acid), M2 (cardiac — ↓ HR), M3 (smooth muscle + glands + pupil constriction).

✔ Correct — B: Sympathetic postganglionic neurotransmitter = noradrenaline (norepinephrine) at most effectors (acts on α1, α2, β1, β2, β3 adrenoceptors). Exceptions: (1) sweat glands (eccrine) = ACh on M3 (cholinergic sympathetic — anomaly); (2) adrenal medulla = releases adrenaline (80 %) + noradrenaline (20 %) directly to blood — single-neuron innervation from splanchnic preganglionic fibres; (3) renal vasodilation via dopamine (DA1 receptor). NT + receptor pairs across ANS: Pre-ganglionic sympathetic = ACh on nicotinic N_N (ganglionic) — ganglion blockers trimethaphan + hexamethonium block both sympathetic + parasympathetic. Post-ganglionic sympathetic = NE on adrenergic α / β (except sweat = ACh / M3). Pre-ganglionic parasympathetic = ACh on N_N. Post-ganglionic parasympathetic = ACh on muscarinic M1-M5. NMJ = ACh on N_M (muscle nicotinic). Catecholamine synthesis (in sympathetic neurons + adrenal medulla): Tyrosine → DOPA (tyrosine hydroxylase, rate-limiting) → Dopamine (DOPA decarboxylase) → NE (dopamine β-hydroxylase) → Epinephrine (PNMT, adrenal only — induced by cortisol). Storage in vesicles (VMAT). Release by Ca²⁺-dependent exocytosis. Termination: reuptake (NET into presynaptic neuron — uptake 1; extraneuronal — uptake 2), degradation by MAO (intracellular) + COMT (extracellular) → metanephrines + VMA (urinary markers for pheochromocytoma). Blockers: reserpine (depletes VMAT vesicles), tyramine (releases NE — cheese effect with MAOIs), cocaine / TCAs (NET inhibitors).

✔ Correct — C: Neuronal action potential (Hodgkin + Huxley 1952 squid giant axon): (1) Resting membrane potential (~ -70 mV) = dominated by K+ leak channels (E_K ~ -90 mV) + Na+/K+ ATPase (3 Na+ out / 2 K+ in, electrogenic). (2) Stimulus → local depolarisation — if threshold reached (~ -55 mV), voltage-gated Na+ channels open → massive Na+ influx (rapid depolarisation toward E_Na ~ +60 mV, overshoot to ~ +40 mV). (3) Repolarisation — voltage-gated Na+ channels inactivate (within ~ 1 ms) + voltage-gated K+ channels open (delayed rectifier) → K+ efflux. (4) Hyperpolarisation (undershoot) — K+ channels close slowly, membrane briefly more negative than rest. (5) Na+/K+ ATPase restores ion gradients. All-or-none law. Refractory periods: absolute (Na+ channels inactivated — no AP regardless of stimulus; ~ 1 ms); relative (some Na+ channels recovered + K+ channels still open — AP possible with suprathreshold stimulus). AP propagation: unmyelinated = continuous (slow ~ 0.5-2 m/s); myelinated = saltatory jumping between nodes of Ranvier (fast up to 120 m/s for Aα fibres). Conduction velocity ∝ axon diameter × √myelination. Cardiac AP different: SA node (phase 4 pacemaker depolarisation by funny current I_f, then Ca²⁺); ventricular (phase 0 Na+, phase 1 K+ transient, phase 2 plateau Ca²⁺, phase 3 K+, phase 4 resting). Ion channel toxins: tetrodotoxin TTX (puffer fish) + saxitoxin (shellfish) block voltage-gated Na+ channels (extracellular); local anaesthetics (lidocaine, procaine) block Na+ intracellularly in inactivated state; tetraethylammonium blocks K+.

✔ Correct — A: Resting membrane potential (RMP) of neuron ~ -70 mV (muscle -90 mV; cardiac contractile -90 mV; SA node -60 mV; smooth muscle -55 mV). RMP set by (1) ion gradients established by Na+/K+ ATPase (3 Na+ out / 2 K+ in per ATP, electrogenic — contributes ~ -10 mV directly); (2) differential membrane permeability — K+ leak channels dominate (P_K >> P_Na). Nernst equation (equilibrium potential for single ion at 37 °C) E_ion = 61/z × log([out] / [in]): E_K ~ -90 mV (intracell 140 mM / extracell 4 mM); E_Na ~ +60 mV (intracell 14 / extracell 142); E_Cl ~ -70 mV (intracell 10 / extracell 110); E_Ca ~ +125 mV (intracell 0.0001 mM / extracell 2.5 mM). Goldman-Hodgkin-Katz (GHK) equation gives actual resting V_m considering multiple ions weighted by permeability. Hypokalaemia → hyperpolarisation + ↑ RMP gap from threshold → ↓ excitability (fatigue, weakness, ileus, arrhythmia U waves); hyperkalaemia → depolarisation (initially ↑ excitability then Na+ channel inactivation → ↓ excitability; peaked T waves, sine waves, asystole). Hypocalcaemia → ↑ Na+ channel excitability → tetany (Chvostek, Trousseau); hypercalcaemia → ↓ excitability (shortened QT, lethargy). Hyponatraemia → ↓ AP amplitude but RMP minimally changed. Driving force on ion = V_m − E_ion. Nernst-inverted intracellular = electronegative (K+ out > K+ in drives K+ out → RMP toward E_K).

✔ Correct — B: CSF produced by choroid plexus (modified ependymal cells + fenestrated capillaries) in lateral (mainly), 3rd + 4th ventricles. Normal total volume ~ 125-150 mL (adult); daily production ~ 500 mL (turnover 3-4× / day). Secretion rate ~ 20 mL/h. Composition: ultrafiltrate of plasma — colourless, clear, pH 7.33, specific gravity 1.005. Compared to plasma: ↓ protein (15-45 mg/dL), ↓ glucose (~ 2/3 plasma, 40-70 mg/dL), ↓ K+ / Ca²⁺, ↑ Mg²⁺ + Cl-. Cells: 0-5 WBC/μL (mononuclear, no RBC, no neutrophils). Circulation: lateral ventricles → foramen of Monro (interventricular) → 3rd ventricle → cerebral aqueduct (of Sylvius) → 4th ventricle → escapes via foramen of Magendie (median) + 2 foramina of Luschka (lateral) → subarachnoid space + central canal → circulates over brain + spinal cord → reabsorbed via arachnoid villi (granulations) into superior sagittal sinus → venous circulation. Functions: mechanical cushion + buoyancy (brain effective weight reduced from 1400 g to 50 g), nutrient + waste exchange, immunological. CSF pressure normal 5-15 mmHg (70-180 mm H₂O) in lateral recumbent. Hydrocephalus: non-communicating / obstructive (e.g., aqueductal stenosis, Chiari malformation, tumour) vs communicating (↓ arachnoid absorption — post-meningitic / SAH). Normal pressure hydrocephalus (NPH) = Hakim triad — Wet + Wobbly + Wacky (urinary incontinence + gait + dementia); treatable with VP shunt. LP: at L3-L4 / L4-L5 in adults; indicated for meningitis, SAH, MS, GB syndrome (albuminocytological dissociation); CI in ↑ ICP with mass lesion / bleeding diathesis.

✔ Correct — C: Blood-brain barrier = selective permeability barrier between blood + CNS; formed by: (1) non-fenestrated cerebral capillary endothelium with tight junctions (claudin-5, occludin, ZO-1); (2) continuous basement membrane; (3) pericytes; (4) astrocyte end-feet (perivascular glia limitans) — induce + maintain BBB via signals (Wnt, Sonic hedgehog). P-glycoprotein (MDR1, ABCB1) + BCRP efflux pumps expel xenobiotics. Permeable to: lipid-soluble molecules (O₂, CO₂, anaesthetics, ethanol, caffeine, lipophilic drugs), small molecules via transporters (glucose — GLUT1; amino acids — LAT1; monocarboxylates — MCT1; nucleosides), small ions. Impermeable to: most polar / charged / large molecules; hydrophilic drugs; dopamine (give L-DOPA instead via LAT1); insulin (mostly); large proteins. Circumventricular organs (CVOs) lack BBB — area postrema (CTZ — senses emetics, toxins; target of antiemetics e.g. 5-HT3 antagonists ondansetron), subfornical organ + OVLT (osmoreception + thirst + ADH), median eminence (hypothalamic hormones), neurohypophysis (ADH + oxytocin release), pineal gland (melatonin), choroid plexus (though tight junctions here — blood-CSF barrier). BBB disruption in stroke, tumour (contrast enhancement), meningitis, MS, sepsis, traumatic brain injury. Blood-CSF barrier = tight junctions of choroid plexus epithelium (ependymal). Mannitol (osmotic diuretic) + ultrasound (focused) can temporarily open BBB for drug delivery.

✔ Correct — A: GABA (γ-aminobutyric acid) = principal inhibitory neurotransmitter in brain (synthesised from glutamate by GAD — glutamic acid decarboxylase, vitamin B6 / pyridoxal phosphate cofactor). Receptors: GABA_A (ionotropic, ligand-gated Cl- channel → hyperpolarisation via Cl- influx → IPSP; site for benzodiazepines [↑ frequency], barbiturates [↑ duration], ethanol, neurosteroids, propofol, etomidate, volatile anaesthetics; flumazenil = benzodiazepine antagonist); GABA_B (metabotropic Gi-coupled → K+ opening + Ca²⁺ closing; activated by baclofen — used in spasticity). Glycine = principal inhibitory NT in spinal cord + brainstem (glycine receptor — strychnine antagonist → tetanic spasm; also co-agonist at NMDA). Glutamate = major excitatory NT (receptors: AMPA, kainate, NMDA ionotropic + 8 metabotropic mGluR groups I-III). Glutamate excitotoxicity → stroke, TBI. Dopamine — nigrostriatal (motor, Parkinson), mesolimbic (reward, addiction, positive schizophrenia symptoms), mesocortical (cognition, negative schizophrenia), tuberoinfundibular (PRL inhibition). Serotonin (5-HT) — raphe nuclei → mood, sleep, appetite. Noradrenaline — locus coeruleus → attention, arousal, stress. Histamine — tuberomamillary nucleus → wakefulness (H1 sedation with antagonists). Acetylcholine — nucleus basalis of Meynert → memory (Alzheimer disease — acetylcholine + cholinergic neurons lost; donepezil / rivastigmine / galantamine = AChE inhibitors). Endogenous opioids — endorphins, enkephalins, dynorphins at μ / δ / κ receptors. Neuropeptides — substance P (pain), CCK, VIP, somatostatin, galanin.

✔ Correct — D: Retina photoreceptors: Rods — ~ 120 million; dim-light / scotopic / night vision; high sensitivity (can detect single photon, slow recovery); no colour discrimination (black + white); rhodopsin pigment (opsin + 11-cis-retinal → all-trans-retinal on light → phototransduction cascade via transducin Gt → PDE → ↓ cGMP → CNG Na+ channel closes → hyperpolarisation); peripheral retina. Cones — ~ 6 million; bright-light / photopic / colour vision; concentrated in fovea centralis + macula (fovea = cone-only, highest visual acuity, no overlying layers); 3 types by photopigment: S (short / blue, ~ 420 nm), M (medium / green, ~ 530 nm), L (long / red, ~ 560 nm). Retina layers (10 layers, light travels INWARD through all to reach outer photoreceptor segments): pigment epithelium (RPE — phagocytose shed outer segments, retinal recycling, blood-retina barrier), photoreceptor (rods + cones), outer limiting membrane, outer nuclear (receptor nuclei), outer plexiform, inner nuclear (bipolar, horizontal, amacrine), inner plexiform, ganglion cell (axons form optic nerve), nerve fibre, inner limiting membrane. Vertical pathway: photoreceptor → bipolar → ganglion cell (axons exit at optic disc = blind spot, no photoreceptors). Lateral modulation: horizontal + amacrine. Visual pathway: retina → optic nerve → optic chiasm (nasal fibres cross) → optic tract → LGN of thalamus → optic radiations (Meyer's loop → temporal → inferior visual field; parietal → superior visual field) → primary visual cortex (V1 / area 17 / calcarine sulcus). Night blindness (nyctalopia) = vitamin A deficiency (retinal precursor) or retinitis pigmentosa (rod loss). Colour blindness = X-linked cone deficiency (red-green most common 8 % males).

✔ Correct — B: Accommodation for near vision — parasympathetic stimulation via CN III (Edinger-Westphal → ciliary ganglion → short ciliary nerves → muscarinic M3 on ciliary muscle) causes ciliary muscle to contract (circular + meridional fibres) → ciliary body moves inward → tension on zonular fibres / suspensory ligaments (of Zinn) slackens → natural elasticity of lens allows it to become more convex / rounded (↑ refractive power, ~ +12 D). Simultaneously: miosis (pupil constricts via sphincter pupillae M3) + convergence (medial recti contract) = "near triad / accommodation reflex". Far vision = opposite: ciliary muscle relaxes → zonules taut → lens flattens. Refractive power of eye ~ 59 D (cornea ~ 43 D fixed + lens ~ 16 D variable). Far point of normal eye = infinity; near point = ~ 25 cm (in young adult). Presbyopia = age-related ↓ lens elasticity → ↓ accommodation (near point recedes; need reading glasses by ~ 40-45 yr). Refractive errors: Myopia (short-sighted — eyeball too long or cornea too curved; image falls in front of retina; correct with concave / minus lens). Hyperopia (long-sighted — eyeball too short; image falls behind retina; correct with convex / plus lens). Astigmatism = irregular corneal curvature → distorted image; correct with cylindrical lens. Presbyopia = convex reading lens. Cataract = lens opacity (age, diabetes, steroid). Glaucoma = ↑ IOP (> 21 mmHg) due to impaired aqueous drainage (primary open-angle via trabecular meshwork or angle-closure) → optic nerve damage + cupping + visual field loss; tx: β-blockers (timolol), prostaglandins (latanoprost), α2 agonists (brimonidine), CAI (acetazolamide, dorzolamide), miotic pilocarpine + surgery. Aqueous humour produced by ciliary processes (non-pigmented epithelium), flows pupil → anterior chamber → trabecular meshwork → canal of Schlemm → episcleral veins.

✔ Correct — A: Rhodopsin ("visual purple") = GPCR in rod disc membranes; consists of opsin (protein, 348 aa, 7TM) covalently bound to 11-cis-retinal (aldehyde form of vitamin A / retinol, via Schiff base with Lys296 of opsin). Phototransduction cascade: Photon absorbed → 11-cis-retinal isomerises to all-trans-retinal → conformational change in opsin (metarhodopsin II, active form) → activates G-protein transducin (Gt; α-subunit with GTP) → activates cGMP phosphodiesterase (PDE6) → hydrolyses cGMP to 5'-GMP → ↓ cytosolic cGMP → cyclic nucleotide-gated (CNG) Na+ / Ca²⁺ channels close → photoreceptor hyperpolarises (from rest ~ -40 mV to ~ -70 mV) → ↓ glutamate release onto bipolar cell → signal propagates. In dark, photoreceptors are depolarised (steady Na+ influx — "dark current") + release glutamate continuously. Retinal is recycled via RPE (visual cycle: all-trans-retinol → 11-cis-retinol → 11-cis-retinal → returns to rod outer segment). Vitamin A / retinol deficiency → night blindness (nyctalopia — impaired rod function) + xerophthalmia + Bitot spots + keratomalacia → blindness (major cause in developing countries; WHO supplementation program). Cone photopigments — photopsins (S / M / L) + 11-cis-retinal; colour vision (trichromatic theory Young-Helmholtz + opponent-process theory Hering). Dark adaptation — biphasic curve: cones adapt in ~ 5 min, rods in ~ 20-30 min; rhodopsin regeneration is rate-limiting. Light adaptation — rapid (Ca²⁺ feedback, pigment bleaching, pupil constriction).

✔ Correct — C: Middle ear ossicles (mnemonic "MIS" / "Many Indians Sleep"): Malleus (hammer — attached to tympanic membrane / eardrum) → Incus (anvil) → Stapes (stirrup — footplate attached to oval window, smallest bone ~ 3 mm). Ossicles provide ~ 22× amplification (17× lever action + 20× area ratio of TM to oval window) to overcome impedance mismatch between air (external) + fluid (inner ear perilymph). Middle-ear muscles: tensor tympani (innervated by CN V3, pulls malleus inward → dampens loud sounds) + stapedius (innervated by CN VII, pulls stapes → protects cochlea — stapedius reflex; smallest skeletal muscle). Facial nerve palsy (Bell) → ↓ stapedius → hyperacusis. Eustachian (auditory) tube connects middle ear → nasopharynx, equalises pressure; dysfunction → effusion / otitis media (common in children because Eustachian tube is shorter + more horizontal). Ear anatomy (3 parts): External — pinna / auricle + external auditory meatus (outer 1/3 cartilage — ceruminous glands — inner 2/3 bone) + tympanic membrane (TM, eardrum). Middle — air-filled cavity with ossicles + 2 windows (oval entrance, round pressure release) + Eustachian tube + mastoid air cells (mastoiditis). Inner — bony + membranous labyrinth in petrous temporal bone: cochlea (hearing, 2.5 turns, spiral; perilymph Na+-rich fills scala vestibuli + tympani; endolymph K+-rich fills scala media with organ of Corti — hair cells with stereocilia → AP in CN VIII); vestibule (saccule + utricle — linear acceleration + gravity via otoliths on maculae); 3 semicircular canals (anterior, posterior, lateral — angular acceleration via ampullary crista with cupula). Place theory (Békésy — high frequency near oval / base, low near apex / helicotrema) + frequency / volley theory. Conductive deafness (external + middle — cerumen, OM, otosclerosis — Rinne BC > AC on affected side; Weber lateralises to affected ear) vs sensorineural (inner + CN VIII — presbycusis, noise, ototoxic drugs: aminoglycosides, cisplatin, loop diuretics, salicylate — Rinne AC > BC; Weber lateralises away from affected).

✔ Correct — D: 5 basic tastes: Sweet (T1R2 / T1R3 GPCR — sugars, artificial sweeteners, some amino acids), Sour (H+ via acid-sensing / PKD2L1 / OTOP1 channels — citric + acetic acids), Salty (ENaC Na+ channel — Na+, Li+), Bitter (T2R family ~ 25 GPCRs — many natural toxins + alkaloids — evolutionary defence), Umami (T1R1 / T1R3 — monosodium glutamate, aspartate, ribonucleotides IMP + GMP; identified by Ikeda 1908 from kombu seaweed; 5th taste recognised). Taste receptor cells in taste buds (~ 5000-10 000 in humans) located on papillae: fungiform (anterior 2/3, mushroom-shaped), circumvallate / vallate (V-shaped row at terminal sulcus, posterior; largest), foliate (posterior lateral). Filiform papillae = most numerous but NO taste buds (tactile + thermal only). Taste pathway: anterior 2/3 → chorda tympani (CN VII) → posterior 1/3 → CN IX → epiglottis + root → CN X → all converge on nucleus of solitary tract (medulla) → VPM thalamus → gustatory cortex (insula + frontal operculum, Brodmann 43). Modifiers: gymnemic acid (blocks sweet), miraculin (sweetens sour — miracle fruit), cynarin (artichoke — sweet water aftertaste). Myth debunked: "tongue map" with specific regions is incorrect — all tastes can be sensed across the entire tongue. Chemesthesis (not taste): spicy / hot (capsaicin → TRPV1 channel), menthol / cold (TRPM8), astringency (tannins precipitate proteins). Flavour = taste + smell (retronasal olfaction) + texture + temperature + trigeminal. Ageusia = loss of taste; hypogeusia = reduced. COVID-19 → anosmia + ageusia (via ACE2 + TMPRSS2 damage to olfactory support cells).

✔ Correct — D: Sino-atrial (SA) node = primary pacemaker — located at superior part of right atrium, near opening of SVC (Keith-Flack 1907). Intrinsic rate 60-100 bpm. Pacemaker current I_f ("funny" current, HCN channels = hyperpolarisation-activated cyclic-nucleotide-gated, permeable to Na+ + K+) causes slow spontaneous phase-4 depolarisation from ~ -60 mV → threshold ~ -40 mV → AP dominated by L-type Ca²⁺ channels (phase 0, slow upstroke; no fast Na+ phase here). Vagal (M2) → ↓ I_f + ↑ K+ → slows HR; sympathetic (β1) → ↑ I_f + ↑ Ca²⁺ → ↑ HR. Blood supply: SA nodal artery from RCA (60 %) or LCX (40 %). Hierarchy of pacemakers (latent): SA node 60-100 → AV node 40-60 → Bundle of His 30-40 → Purkinje fibres + ventricular 20-40. "Overdrive suppression" keeps latent pacemakers silent. Conduction system: SA node → internodal tracts (Bachmann's bundle to LA; Wenckebach, James, Thorel to AV) → AV node (~ 0.1 s delay allowing atrial contraction to fill ventricles — decremental conduction; only normal electrical path between atria + ventricles) → Bundle of His → L + R bundle branches → Purkinje fibres (fastest conduction ~ 4 m/s) → ventricular myocardium. Blood supply AV node: from RCA (90 %) → inferior MI → heart blocks. Heart blocks: 1° = ↑ PR > 0.20 s; 2° Mobitz I (Wenckebach — progressive PR ↑ until dropped QRS, benign) / Mobitz II (constant PR then dropped beat — risks CHB, pacemaker needed); 3° CHB = complete AV dissociation (escape rhythm from junction / ventricle).

✔ Correct — B: Heart valves (4): AV valves — (1) Tricuspid (R atrium → R ventricle, 3 cusps); (2) Bicuspid / Mitral (L atrium → L ventricle, 2 cusps — resembles mitre). AV valves anchored by chordae tendineae to papillary muscles — prevent prolapse during systole. Semilunar valves (3 cusps each, no chordae) — (3) Pulmonary (R ventricle → pulmonary trunk); (4) Aortic (L ventricle → aorta). Valves auscultation sites: Aortic = 2nd right ICS parasternal; Pulmonary = 2nd left ICS parasternal; Tricuspid = 4th left ICS parasternal (or lower sternal border); Mitral = 5th left ICS mid-clavicular line (apex). Mnemonic "APT M" or "All Physicians Take Money". Heart sounds: S1 "lub" = closure of AV valves (start of systole, mitral + tricuspid); S2 "dub" = closure of semilunar valves (end of systole, aortic A2 + pulmonary P2; physiological split on inspiration). S3 (ventricular gallop, early diastolic, rapid filling — normal in young + children, CHF / volume overload in adults); S4 (atrial gallop, presystolic, atrial kick against stiff ventricle — hypertension, LVH, ischaemia). Valvular disease: MS (mid-diastolic murmur, opening snap, rheumatic heart disease most common); MR (pansystolic); AS (ejection-systolic, radiates carotids; syncope + angina + dyspnoea); AR (early diastolic blowing decrescendo; Corrigan + Austin-Flint). Rheumatic fever — post streptococcal group A pharyngitis (Jones criteria — Joints arthritis + Carditis + Nodules + Erythema marginatum + Sydenham's chorea). Heart chambers: 4 = 2 atria + 2 ventricles. Right circuit = deoxygenated (SVC / IVC → RA → RV → PA → lungs). Left circuit = oxygenated (pulmonary vv → LA → LV → aorta). Left ventricle is thickest (systemic pressure).

✔ Correct — A: Cardiac output (CO) = Heart Rate (HR) × Stroke Volume (SV); normal adult ~ 5 L/min at rest (HR 70 bpm × SV 70 mL). Up to 20-30 L/min in exercise. Stroke Volume = volume ejected per beat = End-Diastolic Volume (EDV ~ 120 mL) − End-Systolic Volume (ESV ~ 50 mL) = ~ 70 mL. Ejection Fraction (EF) = SV / EDV × 100; normal > 55 %; HFrEF < 40 %; HFmrEF 40-49 %; HFpEF > 50 %. Cardiac Index = CO / BSA (m²) = 2.5-4.0 L/min/m². SV determinants: (1) Preload (EDV / venous return; Frank-Starling law — ↑ preload → ↑ SV via ↑ myocyte stretch → ↑ actin-myosin overlap up to optimal length; limited in failing heart — shifted flat curve). (2) Afterload (aortic pressure / systemic vascular resistance — ↑ afterload → ↓ SV; key in HT). (3) Contractility / inotropy (force independent of preload; ↑ by sympathetic β1 / digoxin / dobutamine / milrinone / Ca²⁺; ↓ by β-blockers / CCB / acidosis / hypoxia / ischaemia). HR determinants: sympathetic (↑ via β1) + parasympathetic (↓ via M2 vagal). BP = CO × TPR (total peripheral resistance). MAP = diastolic + 1/3 pulse pressure (pulse pressure = systolic − diastolic). Measured clinically: Fick principle (CO = O₂ consumption / [O₂ arterial − O₂ venous difference]), thermodilution (Swan-Ganz), echocardiography, MRI. Pressure-volume loop: (1) isovolumetric contraction; (2) ejection (SV ejected); (3) isovolumetric relaxation; (4) filling (rapid passive + atrial kick 10-20 %). Wiggers diagram relates pressures, volumes, ECG, heart sounds. Heart failure: systolic ↓ EF + ↑ LVEDP + pulmonary congestion / oedema; diastolic ↓ compliance with preserved EF. Frank-Starling law (1914) — "energy of contraction is a function of initial fibre length".

✔ Correct — C: Normal ECG waves + intervals (standard paper 25 mm/s, 10 mm/mV): P wave = atrial depolarisation (SA → atria via Bachmann's bundle + internodal tracts); < 0.12 s wide, < 2.5 mm tall. PR interval = onset of P → onset of QRS = 0.12-0.20 s (3-5 small squares); reflects AV nodal delay. QRS complex = ventricular depolarisation (0.06-0.10 s, < 0.12 s; wide in BBB / VT / WPW / hyperkalaemia). Q = 1st negative deflection, R = 1st positive, S = 1st negative after R. ST segment = isoelectric, ventricular plateau (phase 2); elevation = STEMI / pericarditis / early repolarisation / LVH; depression = ischaemia / NSTEMI / digitalis / hypokalaemia / strain. T wave = ventricular repolarisation (same direction as QRS except V1); peaked tall T in hyperkalaemia / hyperacute MI; inverted in ischaemia. U wave (prominent in hypokalaemia). QT interval = onset Q → end T = 0.36-0.44 s (corrected QTc by Bazett = QT / √RR); prolonged in long-QT syndrome + hypocalcaemia + class IA/III antiarrhythmics + antibiotics (macrolides, fluoroquinolones, azoles) + antipsychotics → torsades de pointes risk; shortened in hypercalcaemia + digoxin. Atrial repolarisation is hidden within QRS. ECG leads: limb (I, II, III — Einthoven's triangle); augmented (aVR, aVL, aVF); precordial (V1-V6); standard 12-lead views: inferior (II, III, aVF — RCA), lateral (I, aVL, V5-V6 — LCX), anterior (V1-V4 — LAD), septal (V1-V2 — LAD), posterior (reciprocal changes in V1-V3 + V7-V9). Axis: normal -30° to +90°; LAD < -30° (LAH, LBBB, LVH, inf MI); RAD > +90° (RVH, RBBB, PE, lateral MI). Atrial fibrillation: irregular + irregular rhythm + no P waves + irregular RR; CHA2DS2-VASc score for anticoagulation.

✔ Correct — B: Normal adult BP ~ 120 / 80 mmHg (systolic / diastolic). Classification (ACC/AHA 2017): Normal < 120/80; Elevated 120-129/<80; Stage 1 HT 130-139/80-89; Stage 2 HT ≥ 140/90. (JNC-8 / older cutoff: HT ≥ 140/90 with different thresholds per age + comorbidity.) BP = CO × TPR. CO = HR × SV. Pulse pressure (PP) = systolic − diastolic (normal 40 mmHg). Mean arterial pressure (MAP) = DBP + 1/3 PP ~ 93 mmHg (95 mmHg rough); perfusion pressure of organs; target > 65 mmHg in shock. Regulation: Short-term (seconds-minutes) — baroreceptor reflex (high-pressure receptors — carotid sinus + aortic arch → CN IX + X → NTS medulla → efferents modulate HR + contractility + vasomotor tone; sudden BP ↓ → reflex tachycardia + vasoconstriction via ↓ vagal + ↑ sympathetic). Chemoreceptors (carotid + aortic bodies — O₂ / CO₂ / pH). Central volume receptors + atrial stretch (ANP). Long-term (hours-days) — RAAS (↓ renal perfusion or ↓ Na+ or sympathetic → JG cells release renin → angiotensinogen (liver) → Ang I → ACE (lung) → Ang II [vasoconstrictor, ↑ aldosterone, ↑ ADH, thirst, Na+ retention PT] → aldosterone (adrenal cortex zona glomerulosa) → Na+ + H₂O retention + K+ + H+ secretion in distal nephron via ENaC). ADH / vasopressin (SON + PVN → post pituitary; V1 vasoconstriction, V2 aquaporin-2 insertion in collecting duct → H₂O retention). ANP / BNP (atrial + ventricular stretch → natriuresis + vasodilation; BNP = heart failure marker). Hypertension 1° (essential 95 %) vs 2° (renal, endocrine — pheochromocytoma, Conn, Cushing, OSA, CoA). Treatment ABCD: ACE-I / ARB, β-blockers, CCBs, Diuretics + ACEI/CCB-first in blacks. Hypotensive shock types: hypovolaemic, cardiogenic, distributive (septic / anaphylactic / neurogenic), obstructive (tamponade / PE / tension pneumothorax).

✔ Correct — D: Frank-Starling law (Otto Frank 1895, Ernest Starling 1914) — within physiological limits, the greater the end-diastolic volume (preload) / stretch of cardiac muscle fibres, the greater the force of contraction + stroke volume. Mechanism: ↑ sarcomere length (up to ~ 2.2 μm optimum) → ↑ actin-myosin overlap + ↑ Ca²⁺ sensitivity of troponin C + stretch-activated channels → stronger contraction. Matches CO to venous return — ensures both ventricles eject equal stroke volumes + adjusts to shifts in blood volume. Heart failure = flattened / right-shifted Starling curve (poor response to ↑ preload). Laplace law: wall tension = pressure × radius / (2 × wall thickness); relevant in dilated cardiomyopathy + aneurysm. Bainbridge reflex = ↑ atrial stretch → ↑ HR (via afferent vagal fibres + withdrawal of vagal tone). Chronotropy = HR modulation (β1 ↑, M2 ↓). Inotropy = contractility (positive: Ca²⁺, catecholamines, digoxin inhibits Na/K ATPase → ↑ intracellular Na+ → ↓ NCX → ↑ Ca²⁺ → ↑ force; negative: β-blockers, CCBs). Lusitropy = relaxation (↑ by β1 via phospholamban phosphorylation → ↑ SERCA activity). Dromotropy = conduction velocity (↑ β1 / ↓ vagal). Frank-Starling mechanism essential to match LV + RV output beat-to-beat. Response to exercise: Starling recruited modestly; HR + contractility + reduced afterload contribute more to ↑ CO.

✔ Correct — C: S1 "lub" = closure of AV valves (mitral + tricuspid) at start of systole — onset of isovolumetric ventricular contraction; louder + lower pitched + longer than S2; best heard at apex (mitral area, 5th ICS mid-clavicular). Usually M1 precedes T1 (closely). Loud S1 = MS (early, valves wide open), tachycardia, ↑ contractility. Soft S1 = MR, 1° AV block (PR ↑). Variable S1 = AF, 3° heart block. S2 "dub" = closure of semilunar valves (aortic + pulmonary) at end of systole — onset of isovolumetric relaxation; sharper + higher pitched; best heard at base (2nd ICS). Physiological splitting: A2 then P2 on inspiration (↑ venous return delays pulmonary closure). Wide + fixed split in ASD. Paradoxical split (P2 before A2) in LBBB + AS. Single S2 = severe AS / pulm HT. S3 ventricular gallop early diastolic "Kentucky" — rapid passive filling into compliant ventricle; normal in young + pregnancy; abnormal in CHF + MR / AR. S4 atrial gallop presystolic "Tennessee" — atrial kick into stiff ventricle; abnormal in HT, LVH, AS, HCM, ischaemia. Cardiac cycle events: (1) Atrial systole / "atrial kick" contributes ~ 10-20 % of filling. (2) Isovolumetric ventricular contraction — AV valves close (S1), SL still closed. (3) Rapid ejection. (4) Reduced ejection. (5) Isovolumetric relaxation — SL valves close (S2), AV still closed. (6) Rapid passive filling (early diastole — possible S3). (7) Diastasis (slow filling). Systole ~ 1/3 of cycle at rest; diastole ~ 2/3.

✔ Correct — A: Adult RBC (erythrocyte) lifespan = ~ 120 days (4 months). Structure: biconcave disc ~ 7-8 μm diameter × 2 μm thick; anucleate + lacks mitochondria (energy purely glycolytic / Embden-Meyerhof + HMP shunt — for NADPH + glutathione reduction). Flexible cytoskeleton (spectrin + ankyrin + band 3 + band 4.1 + actin). Contains haemoglobin (~ 280 million molecules / cell, ~ 34 % by mass). Surface antigens — ABO (A or B oligosaccharide on H antigen) + Rh (D is main antigen). Produced in red bone marrow (adult — axial + proximal long bones; in fetus — yolk sac → liver + spleen → marrow from month 5). Erythropoiesis: HSC → myeloid CFU → BFU-E → CFU-E → proerythroblast → basophilic → polychromatic → orthochromatic erythroblast → reticulocyte (enters blood; matures in ~ 1 day) → RBC. Regulated by erythropoietin (EPO) — glycoprotein from peritubular fibroblasts of renal cortex (~ 90 %) + liver (~ 10 %) in response to tissue hypoxia (HIF-2α transcription factor stabilised). Requires: B12 + folate (DNA synthesis); iron + B6 (haem); protein (globin); thyroxine + cortisol + androgens (modulators). Deficiencies → anaemia. Destruction: ~ 1 % daily; senescent RBCs removed by splenic macrophages (reticuloendothelial system); haemoglobin → globin (reused aa pool) + haem → iron (recycled via transferrin → ferritin) + bilirubin (unconjugated → liver → conjugated with glucuronic acid by UGT1A1 → excreted in bile → urobilinogen + stercobilin in gut → brown colour of stool; urobilinogen reabsorbed → urine urochrome → yellow). Pathologies: sickle cell disease (HbSS — Glu6Val β-chain, autosomal recessive, protective against falciparum malaria), thalassaemia (α / β globin chain deficiency), hereditary spherocytosis (spectrin / ankyrin mutation → osmotic fragility), G6PD deficiency (X-linked, oxidative haemolysis with primaquine / fava beans / sulfa / naphthalene — Heinz bodies + bite cells), autoimmune haemolytic anaemia, PNH, iron deficiency (microcytic), B12 / folate def (macrocytic), anaemia of chronic disease.

✔ Correct — B: Adult haemoglobin HbA = α₂β₂ (~ 97 %). Each of 4 globin chains carries 1 haem group (protoporphyrin IX + ferrous iron Fe²⁺) that binds 1 O₂ — so each Hb molecule carries 4 O₂. MW ~ 64 500 Da. Other Hbs: HbA2 = α₂δ₂ (~ 2-3 %; ↑ in β-thalassaemia trait); HbF = α₂γ₂ (fetal; higher O₂ affinity than HbA — shifted left — due to ↓ 2,3-BPG binding to γ chains; adult < 1 %; ↑ in haemoglobinopathies; HPFH variant; hydroxyurea ↑ HbF in sickle disease). Embryonic: Gower 1 (ζ₂ε₂), Gower 2 (α₂ε₂), Portland (ζ₂γ₂). Iron state Fe²⁺ (ferrous) binds O₂; Fe³⁺ (ferric, methaemoglobin) cannot → methaemoglobinaemia (congenital NADH-cytochrome b5 reductase / MetHb reductase deficiency; drugs — nitrates, dapsone, benzocaine, nitrobenzene; tx methylene blue + vitamin C). O₂ dissociation curve sigmoidal due to cooperativity (binding 1 O₂ facilitates next — T taut → R relaxed state of Hb). P50 = 27 mmHg normally. Right shift (↑ P50, ↓ affinity — unload to tissues): ↑ H+ (↓ pH; Bohr effect), ↑ CO₂, ↑ temp, ↑ 2,3-BPG (= 2,3-DPG; produced by Rapoport-Luebering shunt in RBC — ↑ in hypoxia / altitude / anaemia / chronic lung disease). Left shift (↑ affinity): ↓ above, HbF, CO, methaemoglobin, stored blood. CO — binds 210× more avidly than O₂ → carboxyhaemoglobin; cherry-red skin; tx 100 % O₂ or HBO therapy. Normal Hb: men 13.5-17.5 g/dL; women 12-15.5 g/dL; newborn 14-24 g/dL. MCV 80-100 fL, MCH 27-33 pg, MCHC 32-36 g/dL. Anaemia definitions (WHO): men < 13, women < 12, pregnant < 11, children < 11.

✔ Correct — C: O-negative = universal packed-RBC donor — RBCs lack A, B + D antigens, so can be given to any ABO + Rh recipient without haemolytic reaction. Used in emergencies when cross-match not possible. AB positive = universal recipient (no anti-A / anti-B antibodies; Rh+ can receive Rh+ or Rh-). For plasma + fresh frozen plasma (FFP), it's the opposite: AB plasma = universal plasma donor (no anti-A / anti-B in plasma); O plasma recipient. ABO blood group system (Landsteiner 1900, Nobel 1930): A antigen = N-acetylgalactosamine + H; B = galactose + H; O = only H antigen. Antibodies are pre-formed IgM (natural; develop at ~ 6 months via exposure to bacterial antigens). Genotypes: I^A I^A / I^A i (A); I^B I^B / I^B i (B); I^A I^B (AB, co-dominance); ii (O). Bombay phenotype = hh → no H antigen → appears as O but cannot receive even O blood (needs Bombay). Rh system = 50+ antigens; D most immunogenic; Rh+ = D-antigen present. Anti-D Ab is IgG (crosses placenta), formed only after exposure (transfusion / prior Rh+ pregnancy). Haemolytic disease of newborn (erythroblastosis fetalis) = Rh- mother sensitised to Rh+ fetal RBCs (usually via prior pregnancy / abortion / amniocentesis). 2nd Rh+ fetus → anti-D crosses placenta → fetal RBC haemolysis → jaundice + anaemia + hydrops fetalis + kernicterus. Prevention: anti-D immunoglobulin (RhoGAM) at 28 weeks + within 72 h of delivery / abortion / trauma. Direct Coombs (DAT) detects Ab-coated RBCs; indirect Coombs (IAT) detects free Ab in serum (cross-match, antenatal screening). Transfusion reactions: acute haemolytic (ABO mismatch, IgM — complement → intravascular haemolysis, fever, pain, DIC, renal failure); febrile non-haemolytic (leukocyte antigens — most common); allergic / anaphylactic (IgA deficient recipients); TRALI; TACO; delayed haemolytic (days-weeks — minor antigens); infection; iron overload with chronic transfusions (chelate with desferrioxamine / deferasirox).

✔ Correct — A: Differential WBC count (adult): Neutrophils 55-65 % (most abundant), Lymphocytes 25-35 %, Monocytes 3-8 %, Eosinophils 1-4 %, Basophils 0-1 %. Mnemonic "Never Let Monkeys Eat Bananas" (N > L > M > E > B). In children ≤ 4 yr lymphocytes predominate. Total WBC 4000-11 000 / μL. Granulocytes: Neutrophil (polymorphonuclear, 3-5 lobes; lifespan 6-10 h blood / 1-2 d tissue; first responders in acute bacterial infection + inflammation; phagocytose + release ROS / NETs; ↑ in bacterial infection, stress, steroids; ↓ in viral, sepsis, chemo, autoimmune — neutropenia < 1500). Left shift = immature band cells in blood (infection). Eosinophil (bilobed, red / eosinophilic granules — major basic protein + ECP + EDN + EPO); parasitic infections (helminths — kill via MBP); allergy + asthma + hypersensitivity; ↑ in Churg-Strauss, hypereosinophilic syndrome (NAACP — Neoplasm, Asthma, Allergy, Collagen vasc, Parasite). Basophil (bilobed hidden by dark basophilic granules — histamine + heparin + leukotrienes); IgE-mediated hypersensitivity; CML (↑ basophils). Tissue-resident = mast cells (similar function). Agranulocytes: Lymphocytes — B (bone-marrow matured → plasma cells → antibody IgM → IgG/A/E via class switching in germinal centres; memory B); T (thymus matured: CD4 helper Th1 / Th2 / Th17 / Treg / Tfh — MHC II; CD8 cytotoxic — MHC I; memory T); NK (innate, MHC-less kill, perforin + granzyme); B cells ~ 10-20 %, T cells ~ 70-80 %, NK ~ 5-15 % of circulating lymphocytes. Monocyte — largest WBC (12-20 μm), kidney-bean nucleus; differentiate into tissue macrophages (Kupffer = liver, alveolar, microglia = brain, osteoclast = bone, Langerhans = skin, dendritic = lymph); antigen-presenting cells (MHC II); ↑ in chronic infections (TB, syphilis), EBV, Hodgkin, autoimmune.

✔ Correct — B: Platelets (thrombocytes) = anucleate cytoplasmic fragments shed from megakaryocytes (large multinucleate polyploid precursors in bone marrow; ~ 2000-3000 platelets per megakaryocyte). Regulation by thrombopoietin (TPO) — from liver (mostly) + kidney + bone marrow stroma; MPL receptor on megakaryocytes + platelets. Size 2-4 μm (small), lifespan 8-10 days (cleared by splenic macrophages). Normal count 150 000-450 000 / μL. Contain: α-granules (fibrinogen, factor V, vWF, PDGF, TGF-β); dense granules / δ (ADP, ATP, Ca²⁺, 5-HT / serotonin, histamine); lysosomes. Surface GPIb (binds vWF), GPIIb/IIIa (aka αIIbβ3 — binds fibrinogen). Haemostasis (3 phases): (1) Primary — vascular spasm (via endothelin, reflex) + platelet adhesion (GPIb to vWF on exposed collagen) + activation (shape change, granule release — ADP, TXA2 via COX-1, serotonin) + aggregation (GPIIb/IIIa + fibrinogen bridges) → platelet plug. (2) Secondary = coagulation cascade → fibrin mesh stabilises plug. (3) Fibrinolysis — plasminogen → plasmin (via tPA / urokinase) → fibrin degradation (D-dimer, FDPs). Disorders: Thrombocytopenia (< 150) = petechiae + epistaxis + bleeding — ITP (anti-GPIIb/IIIa Ab), TTP (ADAMTS13 deficiency → vWF large multimers; MAHA + thrombocytopenia + fever + AKI + neuro), HUS (Shiga-toxin, children), DIC, HIT (heparin-induced — PF4 + heparin complex Ab, thrombosis + thrombocytopenia), HELLP. Platelet function disorders: Bernard-Soulier (GPIb deficiency — large platelets, ↑ BT), Glanzmann's thrombasthenia (GPIIb/IIIa — no aggregation), storage pool disease, aspirin (irreversible COX-1 inhibition — 7-10 d). Antiplatelet drugs: aspirin (COX-1 irreversible); clopidogrel + prasugrel + ticagrelor (P2Y12 ADP receptor); abciximab + eptifibatide + tirofiban (GPIIb/IIIa); dipyridamole (PDE inhibitor); cilostazol.

✔ Correct — A: Coagulation cascade (classical model): Intrinsic pathway ("contact" — collagen + HMWK + prekallikrein / kallikrein activate XII → XIIa → XI → XIa → IX → IXa + VIIIa (plus Ca²⁺ + phospholipid) → X → Xa). Activated by exposed subendothelial collagen. Measured by aPTT (activated partial thromboplastin time). Extrinsic pathway (tissue factor — faster in vivo): Tissue factor (TF, III) from damaged endothelium + VII → VIIa + Ca²⁺ → X → Xa. Measured by PT / INR (prothrombin time). Common pathway: Xa + Va + Ca²⁺ + phospholipid (prothrombinase complex) → Prothrombin (II) → Thrombin (IIa). Thrombin → Fibrinogen (I) → Fibrin monomers → polymerise → stabilised by Factor XIIIa (transglutaminase) cross-links → stable clot. Thrombin also activates V, VIII, XI, XIII + platelets (positive feedback). Vitamin K-dependent factors (γ-carboxylation of Glu residues enables Ca²⁺ binding): II (prothrombin), VII, IX, X + anticoagulants Protein C + Protein S (mnemonic "1972 + PC + PS"). Vitamin K cycle: VKORC1 reduces oxidised vitamin K (warfarin inhibits VKORC1; reversed by vitamin K / FFP / PCC / idarucizumab for dabigatran). Natural anticoagulants: Antithrombin III (inactivates IIa + Xa + others; potentiated by heparin 1000×); Protein C (activated by thrombin + thrombomodulin → degrades Va + VIIIa with Protein S cofactor); TFPI. Anticoagulant drugs: Heparin (UFH + LMWH — enoxaparin, dalteparin — antithrombin ↑ action; monitored by aPTT for UFH; anti-Xa for LMWH; reversed by protamine); warfarin (vit K antagonist, narrow TI, monitor INR target 2-3 / 2.5-3.5 for mech valves, interacts with CYP2C9 + VKORC1); DOACs (dabigatran — direct thrombin; rivaroxaban + apixaban + edoxaban — direct Xa — minimal monitoring; reversed by idarucizumab or andexanet alfa); fondaparinux (synthetic anti-Xa). Haemophilia: A (F VIII, X-linked, most common); B (F IX, Christmas disease); C (F XI, autosomal). von Willebrand disease = ↓ vWF → impaired platelet adhesion + ↓ F VIII stabilisation; most common inherited bleeding disorder; ↑ BT + aPTT; tx DDAVP / desmopressin.

✔ Correct — C: Vitamin K-dependent clotting factors: II, VII, IX, X (mnemonic "1972" — second Nixon term) + natural anticoagulants Protein C + Protein S + Protein Z. Vitamin K is cofactor for γ-glutamyl carboxylase, which adds a carboxyl group to specific glutamate residues on these factors → Gla domains bind Ca²⁺ + phospholipid surfaces — essential for activation. Vitamin K cycle: reduced K → oxidised K epoxide → regenerated by VKORC1 (vitamin K epoxide reductase complex 1) → re-enters cycle. Warfarin (+ other coumarins — dicumarol, acenocoumarol) inhibits VKORC1 → depletes active reduced vitamin K → ↓ γ-carboxylation → non-functional factors (PIVKA proteins). Onset 24-72 h (depends on clearance of existing factors: VII shortest t1/2 ~ 6 h → earliest ↑ PT; II longest ~ 60 h → slowest effect). Warfarin initially paradoxically pro-thrombotic (Protein C has short t1/2 ~ 8 h → depletes before II and X → transient hypercoagulable state → skin necrosis risk esp in Protein C deficiency; bridge with heparin for 5 days). Vitamin K sources: K1 (phylloquinone — green leafy vegetables — spinach, broccoli, kale — dietary); K2 (menaquinone — gut bacteria + cheese + natto); K3 (menadione — synthetic). Neonatal vitamin K IM at birth to prevent haemorrhagic disease of newborn (HDN — sterile gut + low placental transfer). Monitoring warfarin: PT / INR (target 2-3 usual; 2.5-3.5 mechanical mitral valve). Interactions — CYP2C9 substrates + VKORC1 polymorphism; ↑ effect (bleeding) with amiodarone, cimetidine, TMP-SMX, metronidazole, antibiotics (↓ gut flora → ↓ K2), fluconazole; ↓ effect with rifampin, carbamazepine, phenytoin, barbiturates, St John's wort, vitamin K-rich foods. Reversal: vitamin K (phytomenadione) IV / PO, FFP, PCC (prothrombin complex concentrate — faster + safer than FFP), recombinant F VIIa. Anticoagulant review: heparin (aPTT / anti-Xa; reversal protamine; HIT risk); warfarin (INR; reversal vit K / PCC); DOACs (no routine monitoring; apixaban + rivaroxaban factor Xa inhibitors; dabigatran direct thrombin inhibitor; reversal idarucizumab for dabigatran, andexanet alfa for Xa).

✔ Correct — D: Erythroblastosis fetalis / haemolytic disease of newborn (HDN) = antibody-mediated fetal RBC destruction, usually due to Rh (D antigen) incompatibility. Mechanism: Rh- mother previously exposed to Rh+ blood (usually prior Rh+ pregnancy via feto-maternal transfusion at delivery / miscarriage / abortion / amniocentesis / trauma / mismatched transfusion) → mother produces anti-D IgG antibodies. In subsequent Rh+ pregnancy, IgG (only IgG crosses placenta, IgM does not) crosses placenta → binds + destroys fetal RBCs → fetal anaemia + extramedullary haematopoiesis (→ hepatosplenomegaly; "erythroblasts" in fetal blood — hence name) + heart failure + hydrops fetalis + hyperbilirubinaemia (unconjugated) → kernicterus (basal ganglia staining → CP, deafness, death). First Rh+ pregnancy usually spared (sensitisation occurs at delivery). Prevention: Anti-D immunoglobulin (RhoGAM, Rhesuman) 300 μg IM at 28 weeks gestation + within 72 h of delivery of Rh+ baby / abortion / amniocentesis / antepartum bleed / trauma / invasive procedures — passively binds + clears Rh+ fetal cells before maternal immune system responds. Kleihauer-Betke test estimates volume of fetomaternal haemorrhage → guides anti-D dose. Diagnosis: antenatal — maternal indirect Coombs (IAT) screen; fetal — Doppler middle cerebral artery peak systolic velocity (↑ in anaemia); amniotic bilirubin (ΔOD450 Liley chart); fetal blood sampling. Postnatal: direct Coombs (DAT +), raised bilirubin, hyperbilirubinaemia, anaemia, nucleated RBCs. Treatment: intrauterine transfusion (O-, Rh- packed RBCs via umbilical vein); after delivery — phototherapy + exchange transfusion (if severe). ABO incompatibility also causes HDN (O mother with A or B baby; anti-A / anti-B IgG subclass crosses placenta) — but generally milder + first-pregnancy onset (natural IgM predominates + fetal ABO antigens less expressed). Other minor antigens (Kell, Duffy, Kidd) can cause HDN too.

✔ Correct — B: Ferritin = primary intracellular iron storage protein (hollow apoferritin shell — 24 subunits — stores up to 4500 Fe³⁺ atoms as ferric hydroxyphosphate core). Stored in liver (hepatocytes + Kupffer), spleen, bone marrow macrophages. Serum ferritin = reliable marker of body iron stores (but acute-phase reactant — ↑ in inflammation / infection). ↓ serum ferritin = iron deficiency anaemia (most specific marker); ↑ ferritin = hereditary haemochromatosis (HFE gene C282Y / H63D), transfusion iron overload, inflammation, hepatitis, liver disease, malignancy. Hemosiderin = ferritin aggregates, insoluble, visible on Prussian blue stain — chronic iron overload. Transferrin = main iron TRANSPORT protein in plasma (β1-globulin from liver; 2 Fe³⁺ binding sites; ~ 30 % saturated normally). Transferrin saturation = serum iron / TIBC × 100 %; normal 20-50 %. ↓ TSAT + ↑ TIBC + ↓ ferritin = iron deficiency. ↑ TSAT + ↑ ferritin = haemochromatosis / overload. Hepcidin (liver peptide) = master regulator — binds + degrades ferroportin (iron exporter on enterocytes + macrophages) → ↓ iron absorption + ↓ release. ↑ hepcidin by IL-6 (inflammation) → anaemia of chronic disease (functional iron deficiency). ↓ hepcidin in haemochromatosis. Iron absorption: duodenum + proximal jejunum; heme iron (meat) — heme carrier protein 1 (HCP1); non-heme iron — reduced by ascorbate / cytochrome b (Fe³⁺ → Fe²⁺) → DMT1 uptake; enterocyte exports via ferroportin + hephaestin (oxidises to Fe³⁺) → transferrin in plasma. Absorption ↑ by ascorbate, meat, low pH; ↓ by phytate (grains), tannates (tea), calcium, antacids, tetracycline. Haptoglobin = binds free Hb (from intravascular haemolysis) → liver clearance; ↓ haptoglobin = haemolysis marker. Ceruloplasmin = copper carrier; ↓ in Wilson disease + Menkes. Iron deficiency anaemia — microcytic hypochromic, ↓ Hb / MCV / MCH / ferritin / serum Fe / TSAT; ↑ TIBC + RDW. Causes: blood loss (GI > menstrual), dietary, pregnancy, malabsorption (coeliac, post-gastrectomy).

✔ Correct — A: Bilirubin = waste product of haem catabolism (primarily from senescent RBC haemoglobin — 85 %; also myoglobin + cytochromes — 15 %). Pathway in reticuloendothelial macrophages (spleen, liver Kupffer, bone marrow): Haem → Biliverdin (by haem oxygenase — HO1 / HO2 — releases Fe²⁺ recycled + CO [minor physiological signaller]) → Biliverdin → Bilirubin (by biliverdin reductase — NADPH-dependent). Unconjugated (indirect) bilirubin = lipid-soluble, transported to liver bound to albumin (cannot cross BBB normally, but displaced by drugs — sulfa, ceftriaxone → risk of kernicterus in neonates with physiological jaundice). In hepatocyte: uptake → conjugation with 2 glucuronic acids by UGT1A1 (UDP-glucuronosyltransferase) → bilirubin diglucuronide = conjugated (direct) bilirubin (water-soluble). Excreted in bile → intestine. Gut bacteria convert to urobilinogen → (1) stercobilin (brown faeces); (2) enterohepatic recirculation (some reabsorbed → liver); (3) kidney → urobilin (yellow urine). Normal total bilirubin < 1.2 mg/dL (direct < 0.3). Jaundice (yellow skin / sclera) visible at > 2-3 mg/dL. Types: (1) Pre-hepatic / haemolytic — ↑ unconjugated (haemolysis — SCD, thalassaemia, G6PD, AIHA; ineffective erythropoiesis; large haematoma resorption). (2) Hepatic — ↑ both (hepatitis, cirrhosis, Gilbert UGT1A1 promoter polymorphism 3-10 % pop, mild; Crigler-Najjar I absent UGT1A1 → severe kernicterus; CN II partial; Dubin-Johnson — MRP2 defect → ↑ conjugated with black liver; Rotor — mild). (3) Post-hepatic / obstructive — ↑ conjugated (gallstones, cholangiocarcinoma, pancreatic head ca, PSC, PBC — pale stools + dark urine + pruritus — bile acids). Neonatal jaundice: physiological 2-3 day (immature UGT1A1); pathological < 24 h / > 2 wk (haemolysis — ABO/Rh, G6PD; bile duct atresia — requires Kasai portoenterostomy). Kernicterus = unconjugated bilirubin staining of basal ganglia in neonates → permanent neurological damage. Treatment neonatal: phototherapy (450-460 nm blue-green light → isomerises bilirubin to water-soluble forms), exchange transfusion for severe.

✔ Correct — C: Spleen = largest lymphoid organ (~ 150 g, 12 × 7 × 3 cm; rule 1-3-5-7-9-11 — 1 × 3 × 5 inches, 7 oz, between 9th-11th ribs). Located left hypochondrium / LUQ; encapsulated (fibroelastic + smooth muscle); supplied by splenic artery (from coeliac trunk) + drained by splenic vein into portal vein; lymphatics. Structure: White pulp (lymphoid — PALS around central arteriole with T cells; germinal centres of B cells + follicles; marginal zone — antigen presentation); Red pulp (splenic cords of Billroth + venous sinusoids — RBC filtration, macrophages); marginal zone. Functions: (1) Haematopoiesis — fetal (3-7 months) + emergency in adults; (2) Filtration — removes senescent / abnormal RBCs, Howell-Jolly bodies (nuclear remnants), Heinz bodies (denatured Hb in G6PD def), parasites, bacteria — especially encapsulated; (3) Iron recycling — haem → bilirubin + Fe²⁺; (4) Immune — B + T lymphocyte activation, Ab production (esp. IgM against polysaccharide antigens of encapsulated bacteria); (5) Reservoir — ~ 1/3 platelets + some RBCs. Splenectomy (trauma, ITP, hereditary spherocytosis, hypersplenism) → ↑ risk of overwhelming post-splenectomy infection (OPSI) by encapsulated organisms (mnemonic "SHiN" or "Some Nasty Killers Have Pretty Big Pills" / "No Spleen Can Kick Peoples Heads"): Strep pneumoniae, H influenzae type b, N meningitidis, Group B Strep, E coli, Klebsiella, Pseudomonas, Salmonella — prophylactic immunisations (PPSV23 + PCV13 + Hib + Men conjugate vaccines) + lifelong penicillin prophylaxis (or daily phenoxymethylpenicillin). Blood smear post-splenectomy: Howell-Jolly + target cells + Heinz + Pappenheimer + thrombocytosis + acanthocytes. Splenomegaly causes: portal hypertension (cirrhosis), haematological (CML, CLL, myelofibrosis, lymphoma, thalassaemia, SCD), infections (malaria, EBV, kala-azar / leishmaniasis, TB, endocarditis), storage (Gaucher, Niemann-Pick), congestive.

✔ Correct — D: Thoracic duct = largest lymphatic vessel (~ 38-45 cm). Begins at cisterna chyli (dilated sac at L1-L2, in front of upper lumbar vertebrae); ascends through aortic hiatus (T12, with aorta + azygos + vagus); enters left subclavian vein at the junction with left internal jugular vein (= left venous angle / jugulo-subclavian junction). Drains: lower limbs, abdomen + pelvis, left upper limb, left side of head + neck, left thorax, left lung — i.e., ~ 3/4 of body. Right lymphatic duct (~ 1 cm short trunk) drains right upper body — right arm + right head/neck + right thorax + right lung — into right venous angle (right subclavian + right IJ junction). Chyle (fat-laden intestinal lymph from lacteals — triglyceride-rich chylomicrons) enters thoracic duct at cisterna chyli — hence "chyle-containing"; damage (surgery, trauma) → chylothorax (milky pleural effusion) / chylous ascites. Lymphatic system: capillaries (blind-ended, overlapping endothelium — low-pressure drainage; permeable) → collecting lymphatics (have valves, similar to veins) → trunks → ducts → venous system. Daily lymph ~ 3-4 L returned. Functions of lymphatic system: (1) return interstitial fluid + protein to blood (prevents oedema); (2) absorb dietary fats + fat-soluble vitamins (A, D, E, K) from intestine (lacteals); (3) immune surveillance — filter lymph via nodes; (4) transport immune cells. Lymph nodes (500-600 total): cortex (B cells in follicles with germinal centres + primary + secondary), paracortex (T cells + HEVs for lymphocyte entry), medulla (medullary cords of plasma cells + sinuses for exit). Afferent lymphatics → subcapsular sinus → through cortex → medullary sinus → efferent lymphatic (at hilum). Virchow's node = left supraclavicular LAD from gastric / abdominal malignancy. Sister Mary Joseph = periumbilical. Sentinel node = first draining node (melanoma, breast ca — biopsy guides staging). MALT = mucosa-associated lymphoid tissue (Peyer's patches in ileum, appendix, tonsils — Waldeyer ring, bronchial, nasal). Thymus: T-cell maturation (positive + negative selection), ↑ in children; involutes post-puberty (fatty replacement). Hassall's corpuscles in medulla. DiGeorge syndrome = 22q11 deletion → thymic aplasia + CATCH-22.

✔ Correct — B: Thymus = primary lymphoid organ for T cell maturation ("T" for thymus). Located in anterior superior mediastinum behind sternum; bi-lobed; encapsulated; divided into lobules — each with outer cortex (densely packed thymocytes) + inner medulla (mature T cells + Hassall's corpuscles — whorls of epithelial reticular cells — histologic hallmark). Maximum size at puberty (~ 40 g); involutes with age (fatty replacement — thymic involution; can reactivate post-chemo). T cell development: Lymphoid progenitor from bone marrow enters thymic cortex as double-negative (CD4- CD8-) → TCR β-chain rearrangement (RAG-1/2; V(D)J recombination) → double-positive (CD4+ CD8+) → TCR α-chain rearrangement → positive selection (in cortex — thymocytes whose TCR binds self-MHC with low-moderate affinity survive; others die — "MHC restriction") → migrate to medulla → negative selection (TCRs that bind self-antigens strongly undergo apoptosis — eliminates autoreactive clones; AIRE gene enables medullary thymic epithelial cells to express peripheral self-antigens like insulin; AIRE mutation → APECED / autoimmune polyendocrinopathy) → single-positive (CD4+ helper MHC II-restricted or CD8+ cytotoxic MHC I-restricted) → exit to periphery as naïve T cell. Primary lymphoid organs: thymus (T cells), bone marrow (B cells — bursa-equivalent in mammals; "bursa of Fabricius" in birds, discovered by Glick 1956). Secondary lymphoid organs: lymph nodes, spleen, MALT (Peyer's patches, tonsils — Waldeyer ring: palatine + pharyngeal / adenoid + tubal + lingual, appendix, bronchial, nasal). Here antigen meets lymphocytes, activation occurs. T cell subsets: Th1 (IFN-γ, cellular immunity, macrophage activation; TB); Th2 (IL-4, IL-5, IL-13, humoral + allergy + anti-helminth); Th17 (IL-17, extracellular bacteria + fungi; psoriasis, IBD, RA); Treg (FoxP3, IL-10, TGF-β — peripheral tolerance); Tfh (help B cells in germinal centres). CD8 CTL kills via perforin + granzyme + Fas-FasL. NK cells (innate CD56+, no TCR) kill MHC-low cells. Thymic disorders: DiGeorge 22q11 (thymic aplasia — T cell deficiency + hypoparathyroid + cardiac); thymoma (myasthenia gravis association + pure red cell aplasia). CD3 = pan T marker. CD4 / CD8 ratio normal 2 : 1 (inverted < 1 in HIV).

✔ Correct — C: Right lung = 3 lobes (superior + middle + inferior; separated by oblique + horizontal fissures; ~ 10 bronchopulmonary segments). Left lung = 2 lobes (superior + inferior; single oblique fissure; ~ 8-10 segments; left lung smaller because of cardiac notch in superior lobe — accommodates the heart; lingula homolog of right middle lobe). Total 5 lobes. Hilum of each lung = entry of main bronchus + pulmonary artery + pulmonary veins + bronchial vessels + lymphatics + nerves (autonomic + sensory). Right main bronchus is wider, shorter, more vertical → foreign bodies (aspirated peanut, teeth) usually lodge in RIGHT lower lobe (posterior segment in supine patient). Respiratory tree (23 generations): trachea (windpipe, 12 cm, 16-20 C-shaped cartilage rings with trachealis muscle posteriorly; bifurcates at carina at T4-T5 level = sternal angle of Louis) → primary / main bronchi (R + L) → secondary / lobar bronchi → tertiary / segmental → bronchioles (no cartilage, smooth muscle — site of asthmatic constriction) → terminal bronchioles (last conducting, cilia end) → respiratory bronchioles (some alveoli) → alveolar ducts → alveolar sacs → alveoli (~ 300 million, total surface area 70-100 m²). Epithelium changes: pseudostratified ciliated columnar with goblet cells (URT + trachea + bronchi) → simple cuboidal / ciliated (bronchioles, Clara / club cells produce surfactant-like + CC16) → simple squamous (alveoli). Alveoli cells: Type I pneumocyte (95 % surface area, gas exchange, simple squamous); Type II (cuboidal, granules, surfactant production + stem-like regeneration after damage); alveolar macrophage (dust cells). Pleura: visceral (lung) + parietal (thoracic wall); potential pleural space with ~ 5-15 mL serous fluid (lubrication, surface tension). Costal, mediastinal, diaphragmatic, cervical pleurae. Pleuritis — friction rub. Pneumothorax = air in pleura; hemothorax = blood; pleural effusion = fluid (transudate vs exudate by Light's criteria).

✔ Correct — A: Diaphragm = principal muscle of inspiration (~ 70-80 % of work); dome-shaped skeletal muscle separating thorax from abdomen; innervated by phrenic nerve (C3, C4, C5 — "C3-4-5 keeps the diaphragm alive"). Contraction → dome descends (~ 1-1.5 cm quiet; 10 cm deep) → ↑ vertical thoracic volume → ↓ intrapleural pressure (more negative) → ↓ intra-alveolar pressure < atmospheric → air flows in. External intercostals (innervated by intercostal nerves T1-T11) elevate ribs → "bucket handle + pump handle" motion → ↑ AP + lateral thoracic dimensions (contribute 20-30 %). Accessory muscles of inspiration (deep / forced breathing): sternocleidomastoid, scalenes, pectoralis minor, serratus anterior, trapezius, erector spinae → elevate sternum + ribs. Expiration: quiet expiration = passive (elastic recoil of lungs + chest wall); forced expiration uses internal intercostals + abdominal muscles (rectus abdominis, external / internal oblique, transversus abdominis) → push diaphragm up. Mechanics of breathing (Boyle's law P₁V₁ = P₂V₂): Inspiration = ↑ V → ↓ P → air enters (intra-alveolar ~ -1 mmHg below atmospheric); expiration = ↓ V → ↑ P → air out (+1 mmHg). Intrapleural pressure ALWAYS negative in health (-5 mmHg rest, -8 mmHg inspiration; balance between lung elastic recoil inward + chest wall recoil outward) — prevents lung collapse. Pneumothorax → pleural pressure rises to 0 → lung collapses. Lung compliance (ΔV/ΔP) normal ~ 200 mL/cmH₂O; ↑ in emphysema (↓ recoil), ↓ in fibrosis / ARDS / pulmonary oedema / pneumonia (stiffer). Airway resistance — bronchioles with smooth muscle (no cartilage) = main site; ↑ in asthma + COPD; ↓ by β2 agonists (salbutamol / albuterol, salmeterol) + anticholinergics (ipratropium, tiotropium) + theophylline. Diaphragm openings: caval T8 (IVC + right phrenic); oesophageal T10 (oesophagus + vagus anterior + posterior trunks); aortic T12 (aorta + thoracic duct + azygos; technically behind diaphragm).

✔ Correct — B: Pulmonary surfactant secreted by Type II pneumocytes (alveolar type II cells) — cuboidal, granular, contain lamellar bodies. Composition: 90 % phospholipids (mostly dipalmitoyl phosphatidylcholine, DPPC / lecithin — main surface-active component) + phosphatidylglycerol + 10 % surfactant proteins SP-A, SP-B, SP-C, SP-D (SP-B + SP-C spread DPPC; SP-A + SP-D innate immunity / opsonisation). Functions: (1) ↓ alveolar surface tension (Laplace P = 2T/r — smaller alveoli prone to collapse; surfactant makes surface tension proportional to alveolar size → equal pressure in all alveoli + prevents smaller alveoli from emptying into larger ones); (2) prevents atelectasis (especially at end-expiration); (3) ↑ lung compliance (less work to inflate); (4) ↓ capillary fluid transudation (anti-oedema). Production begins ~ week 24 gestation; mature ~ 35 weeks. Preterm babies (< 35 weeks) → Infant respiratory distress syndrome (IRDS / Neonatal RDS / Hyaline membrane disease) — surfactant deficiency → atelectasis + respiratory failure. Antenatal corticosteroids (betamethasone / dexamethasone 24-34 wk) accelerate surfactant maturation in fetus at risk of preterm delivery. Treatment of IRDS: artificial surfactant (Survanta / beractant, Curosurf / poractant alfa, Infasurf / calfactant) given intratracheally + oxygen + CPAP + mechanical ventilation. Amniotic L/S ratio (lecithin / sphingomyelin) > 2 → mature fetal lung; presence of phosphatidylglycerol = best predictor. ARDS (adult) — diffuse alveolar damage, type II pneumocyte dysfunction + surfactant inactivation by exudate → ↓ compliance + hypoxaemia refractory to O₂ + bilateral infiltrates + non-cardiogenic pulmonary oedema; causes sepsis, aspiration, pneumonia, trauma, pancreatitis, transfusion (TRALI); tx low-tidal-volume ventilation (~ 6 mL/kg) + PEEP + prone positioning + treat cause. Alveolar cells: Type I (97 % surface, squamous, gas exchange, cannot divide), Type II (3 % surface but 60 % of cell number — "stem cells" of alveolus, can regenerate after injury including Type I), alveolar macrophages (dust cells — phagocytose particles; heart failure cells contain hemosiderin in pulmonary congestion).

✔ Correct — A: Lung volumes (measured by spirometry except RV): Tidal Volume (TV) = volume inhaled / exhaled in normal quiet breath ~ 500 mL. Inspiratory Reserve Volume (IRV) = additional inspiration above TV ~ 3000 mL. Expiratory Reserve Volume (ERV) = additional expiration below TV ~ 1100 mL. Residual Volume (RV) = air remaining after maximal expiration ~ 1200 mL (CANNOT be measured by spirometry; use helium dilution / nitrogen washout / body plethysmography). Lung capacities (= sum of 2 or more volumes): Inspiratory Capacity (IC) = TV + IRV ~ 3500 mL. Functional Residual Capacity (FRC) = ERV + RV ~ 2300 mL (air in lung at end of normal expiration — equilibrium between inward lung recoil + outward chest recoil). Vital Capacity (VC) = TV + IRV + ERV ~ 4600 mL (maximum expirable air from full inspiration). Total Lung Capacity (TLC) = VC + RV = TV + IRV + ERV + RV ~ 5800 mL. Minute ventilation = TV × RR ~ 500 × 12 = 6 L/min. Alveolar ventilation = (TV − dead space) × RR ~ (500 − 150) × 12 = 4.2 L/min. Dead space = volume not participating in gas exchange: anatomical (conducting airways, ~ 150 mL = 2.2 mL/kg); alveolar (alveoli ventilated but not perfused, e.g., PE); physiological = anatomical + alveolar (near equal to anatomical in health). FEV1 (forced expiratory volume in 1 s) — pivotal spirometry variable. FEV1/FVC ratio: normal ≥ 0.7 (70 %) or lower limit of normal (LLN; age-specific). Obstructive (asthma, COPD, bronchiectasis, cystic fibrosis) = ↓ FEV1 / FVC < 0.7 + ↑ TLC + ↑ RV (air trapping) + ↓ FEF25-75. Restrictive (fibrosis, sarcoidosis, kyphoscoliosis, neuromuscular, obesity) = ↓ TLC + ↓ VC + normal or ↑ FEV1/FVC ratio. DLCO (diffusing capacity for CO) — ↓ in emphysema / fibrosis / PE / anaemia; ↑ in polycythaemia / pulmonary haemorrhage / asthma. Peak expiratory flow rate (PEFR) monitored in asthma. Minute ventilation adjusted by PCO₂; pulmonary ventilation regulated reflexively.

✔ Correct — D: CO₂ transport in blood (3 forms): (1) Bicarbonate (HCO₃⁻) = 70 % — primary form. CO₂ enters RBC → reacts with water via carbonic anhydrase (CA — zinc metalloenzyme; isoforms CA I-XIV): CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻. H⁺ buffered by Hb (now deoxygenated — Haldane effect; imidazole groups of histidine on Hb). HCO₃⁻ exported from RBC into plasma in exchange for Cl⁻ (chloride / Hamburger shift via band 3 / AE1 antiporter) — maintains electroneutrality. In lungs, reverse happens → CO₂ exhaled. (2) Carbaminohaemoglobin = 23 % — CO₂ binds to N-terminal amino groups of Hb globin chains (NOT haem — O₂ binds haem); forms carbamate. Favoured by deoxy-Hb (Haldane effect — deoxy-Hb holds more CO₂ + H⁺ than oxy-Hb; reciprocal of Bohr effect). (3) Dissolved CO₂ = 7 % — as free CO₂ in plasma + RBC water (following Henry's law; ~ 20× more soluble than O₂). PaCO₂ normal 35-45 mmHg; PvCO₂ 45 mmHg; PACO₂ alveolar 40 mmHg. CO₂ production from tissues ~ 200 mL/min; O₂ consumption ~ 250 mL/min (RQ = CO₂/O₂ ~ 0.8 mixed diet; 0.7 fat, 0.85 protein, 1.0 CHO). Carbonic anhydrase inhibitors (acetazolamide, dorzolamide, methazolamide) — used in glaucoma (↓ aqueous humour), altitude sickness (metabolic acidosis opposes respiratory alkalosis), diuretics (weak, proximal tubule — causes HCO₃⁻ loss → metabolic acidosis; pseudotumour cerebri). CA defects → osteopetrosis (CA II — osteoclast dysfunction), proximal RTA. Acid-base: Respiratory acidosis (↑ PaCO₂ — hypoventilation — COPD, sedation, neuromuscular); respiratory alkalosis (↓ PaCO₂ — hyperventilation — anxiety, PE, altitude, ASA early, pain, fever); metabolic acidosis (↓ HCO₃⁻); metabolic alkalosis (↑ HCO₃⁻). Winter's formula: expected PaCO₂ = 1.5 × HCO₃⁻ + 8 ± 2 (for metabolic acidosis compensation). Henderson-Hasselbalch: pH = 6.1 + log[HCO₃⁻/(0.03 × PaCO₂)].

✔ Correct — B: Respiratory regulation: Central chemoreceptors (ventral medulla / retrotrapezoid nucleus) respond to ↓ pH of CSF, which directly reflects ↑ PaCO₂ (CO₂ freely crosses BBB → CA → H⁺ + HCO₃⁻; H⁺ cannot cross BBB, so CSF pH mirrors CO₂). Sensitive, account for ~ 70-80 % of ventilatory response to CO₂. Do NOT respond directly to O₂. Chronic hypercapnia (COPD, OSA) → CSF buffering + ↓ responsiveness → relies on hypoxic drive. Peripheral chemoreceptors — carotid bodies (at bifurcation of common carotid, glossopharyngeal nerve CN IX afferent — sinus nerve of Hering) + aortic bodies (aortic arch, vagus CN X afferent) — respond to ↓ PaO₂ (< 60 mmHg mainly; only 10 % of CO₂ response), ↑ PaCO₂, ↓ pH. Glomus cells — most O₂-sensitive cells in body. Key drive in COPD / chronic retainers. Respiratory centres: (1) Medullary respiratory centre — Dorsal Respiratory Group (DRG — inspiration, drives phrenic + intercostal); Ventral Respiratory Group (VRG — active during forced breathing, expiration + inspiration); Pre-Bötzinger complex (rhythm pacemaker). (2) Pontine respiratory centre — pneumotaxic centre (upper pons — limits inspiration → ↑ rate, ↓ depth); apneustic centre (lower pons — prolongs inspiration if pneumotaxic is damaged). Reflexes: Hering-Breuer inflation reflex (stretch receptors in bronchi + bronchioles → vagal afferent → inhibit inspiration → prevents over-distension; active at high TV > 1.5 L; minor role in adults, more in infants). Deflation reflex. J receptors (juxtacapillary, in alveolar walls → pulmonary oedema / PE → tachypnoea). Cough reflex (via CN X / IX / ISN). Irritant receptors → bronchospasm. Oxyhaemoglobin dissociation curve: sigmoid (cooperativity); P50 = 27 mmHg; SpO₂ > 90 % normal (100 mmHg PaO₂ → 98 %; 60 mmHg → 90 % — clinical threshold; steep portion 40-60 mmHg favours unloading). Right shift (unload to tissue): ↑ H⁺ (Bohr), ↑ PCO₂, ↑ T, ↑ 2,3-BPG (exercise, altitude, anaemia). Left shift: opposite + HbF, CO, methHb, hypothermia.

✔ Correct — C: Gas exchange across respiratory / alveolar-capillary membrane is purely passive diffusion following Fick's law: V̇gas = (A × D × ΔP) / T, where A = area (~ 70-100 m² in adults), D = diffusion coefficient (∝ solubility / √MW; CO₂ is ~ 20× more soluble than O₂ → diffuses faster despite similar gradient), ΔP = partial pressure gradient (PAO₂ ~ 104 mmHg → PaO₂ ~ 100; PACO₂ ~ 40 ← PvCO₂ ~ 45), T = thickness (~ 0.5-1 μm — 6 layers: surfactant fluid, Type I pneumocyte, fused basement membranes, capillary endothelium, plasma, RBC membrane). Normal O₂ equilibration time ~ 0.25 s; blood spends 0.75 s in pulmonary capillary at rest. Diffusion-limited conditions (exercise, altitude, CO, fibrosis): transfer depends on diffusion. Perfusion-limited (O₂ at rest, N₂O, CO₂): transfer depends on blood flow. Normal Henry's law: [gas] = α × P (solubility × partial pressure). Alveolar gas equation: PAO₂ = PiO₂ − (PaCO₂ / R) = FiO₂ (Patm − PH₂O) − PaCO₂ / R = 0.21 (760 − 47) − 40 / 0.8 = 150 − 50 ≈ 100 mmHg. A-a gradient = PAO₂ − PaO₂ (normal < 10-15 mmHg young; ~ age/4 + 4). Elevated A-a in V/Q mismatch, shunt (↑ A-a, not corrected by 100 % O₂), diffusion impairment, ↑ FiO₂. V/Q ratio: normal average 0.8 (ventilation 4 L/min / perfusion 5 L/min). Apex = high V/Q (more V than Q — dead-space-like; PAO₂ high, PACO₂ low — TB preference); base = low V/Q (more Q than V — shunt-like). V/Q = 0 = pure shunt (atelectasis, ARDS); V/Q = ∞ = pure dead space (PE). Hypoxic pulmonary vasoconstriction — unique to pulmonary circulation (↓ PAO₂ → local vasoconstriction to redirect flow to better-ventilated areas); chronic → pulmonary HT + cor pulmonale. Pulmonary circulation: low pressure (25/8 mmHg; mean ~ 15), low resistance; entire CO passes through. Bronchial circulation from aorta supplies conducting airways (not gas exchange). Types of hypoxia: hypoxic (↓ PAO₂ — altitude, hypoventilation), anaemic (↓ Hb — anaemia, CO), circulatory / stagnant (shock), histotoxic (CN poisoning — blocks cytochrome oxidase → can't use O₂).

✔ Correct — A: Spirometry patterns: Obstructive — airflow limitation; ↓ FEV1 more than ↓ FVC → FEV1/FVC < 0.7 (or < LLN). ↑ TLC + ↑ RV + ↑ FRC (air trapping / hyperinflation). Concave expiratory flow-volume curve. Examples: asthma (reversible, ≥ 12 % + ≥ 200 mL improvement in FEV1 post-bronchodilator; eosinophilic), COPD (chronic bronchitis + emphysema; not fully reversible), bronchiectasis, cystic fibrosis (autosomal recessive CFTR Δ508, thick secretions, chronic infection Pseudomonas, Staph), upper airway obstruction. COPD GOLD stages (post-bronchodilator FEV1 % predicted with FEV1/FVC < 0.7): Mild ≥ 80 %; Moderate 50-79 %; Severe 30-49 %; Very severe < 30 %. Management: smoking cessation (most important, ↑ survival), SABA / LABA, LAMA (tiotropium), ICS-LABA combination, roflumilast (PDE4), home O₂ if PaO₂ < 55, pulmonary rehab, vaccines (flu + pneumococcal). Restrictive — impaired expansion; ↓ FVC + ↓ TLC + ↓ RV + normal / ↑ FEV1/FVC (↑ because compliance problem, not flow problem). Examples: intrinsic (pulmonary fibrosis — IPF, asbestosis, silicosis, coal, hypersensitivity pneumonitis, sarcoidosis, RA, SLE); extrinsic (obesity, pregnancy, kyphoscoliosis, pleural disease); neuromuscular (ALS, GBS, myasthenia, poliomyelitis). Flow-volume curve: normal shape but smaller. Asthma = chronic inflammation + reversible bronchoconstriction + airway hyperresponsiveness. Triggers: allergens, cold, exercise, aspirin (Samter's triad), occupational. Eosinophils + Th2 + IgE. Curschmann spirals, Charcot-Leyden crystals, Creola bodies. Tx: SABA (salbutamol), LABA (salmeterol, formoterol), ICS (fluticasone, budesonide — first-line controller), LTRA (montelukast, zafirlukast), LAMA (tiotropium), theophylline, omalizumab (anti-IgE for severe), mepolizumab / reslizumab (anti-IL-5), dupilumab (IL-4/IL-13). Magnesium sulphate for acute severe. Emphysema: alveolar destruction → ↑ compliance, ↓ DLCO; centriacinar (smoking, upper lobes) vs panacinar (α1-antitrypsin deficiency; Z allele on PiZZ; lower lobes; liver cirrhosis). Chronic bronchitis: clinical diagnosis — productive cough ≥ 3 months × 2 consecutive years; Reid index ↑.

✔ Correct — C: Gastric gland cells: (1) Parietal (oxyntic) cell — fundus + body of stomach; secrete HCl (via H⁺/K⁺ ATPase — proton pump; PPI target) + intrinsic factor (IF) (glycoprotein essential for vitamin B12 absorption in terminal ileum). HCl secretion mechanism: CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃⁻ (carbonic anhydrase); H⁺ pumped into lumen via H⁺/K⁺ ATPase; Cl⁻ follows (Cl⁻/HCO₃⁻ exchange exports HCO₃⁻ basolaterally — "alkaline tide" in venous blood post-meal). Stimulated by: vagus (CN X, ACh on M3 — head phase via sight / smell / taste / chewing + gastric phase), histamine (H2 on parietal — from enterochromaffin-like / ECL cells — potentiates Ach + gastrin), gastrin (from antral G cells → CCKB receptor on parietal + ECL → histamine release, most via ECL). Inhibited by: somatostatin (from D cells; low pH → D cells → somatostatin → inhibits G + parietal + ECL; prostaglandins E2 (↓ cAMP + ↑ mucous); secretin; GIP; enterogastric reflex. (2) Chief (peptic / zymogenic) cell — secrete pepsinogen (activated to pepsin by HCl + autocatalytic; active at pH < 3); gastric lipase. (3) G cell (pylorus, antrum) — secrete gastrin (peptide; G17 most active) in response to peptides / amino acids in food, vagal GRP, stomach distension; inhibited by low pH / somatostatin. (4) Mucous neck / surface cells — secrete mucus + HCO₃⁻ (stomach alkaline mucous layer protects epithelium from HCl + pepsin). (5) D cells — secrete somatostatin (paracrine inhibitor). (6) ECL cells — secrete histamine. (7) Enterochromaffin cells — serotonin. Peptic ulcer disease: (a) Duodenal (90 % — due to H. pylori 70-90 %, ↑ acid, usually anterior → pain relieved by food); (b) Gastric (cancer risk, H. pylori 60-70 %, NSAIDs, ↓ mucosal protection; pain ↑ with food). Complications: bleeding, perforation (posterior duodenal erodes into gastroduodenal artery; anterior gastric → air under diaphragm), obstruction, penetration, cancer. Triple therapy: PPI + clarithromycin + amoxicillin (or metronidazole if penicillin allergy) × 14 days; or quadruple with bismuth. Zollinger-Ellison syndrome = gastrinoma (duodenum / pancreas, MEN1 association) → excessive HCl → multiple / refractory ulcers + diarrhoea; dx elevated fasting gastrin + secretin stimulation test. Pernicious anaemia = autoimmune atrophic gastritis → ↓ IF → B12 def → megaloblastic anaemia + subacute combined degeneration.

✔ Correct — B: Vitamin B12 (cobalamin) absorption: (1) Dietary B12 bound to animal protein. (2) Released by HCl + pepsin in stomach. (3) Binds R-binder / haptocorrin from saliva (protects from acid). (4) In duodenum, pancreatic proteases digest R-binder → free B12 binds intrinsic factor (IF) (from parietal cells). (5) IF-B12 complex travels to terminal ileum where it binds cubilin-amnionless receptor on enterocyte → endocytosis. (6) In blood, B12 bound to transcobalamin II (TC II) → delivered to tissues + liver storage (~ 3-5 year supply). B12 deficiency causes: (a) Pernicious anaemia (autoimmune gastritis → ↓ IF; Ab against IF or parietal cells); (b) post-gastrectomy / bariatric surgery; (c) ileal resection / Crohn's / blind loop / bacterial overgrowth; (d) fish tapeworm (Diphyllobothrium latum); (e) strict vegan diet (B12 only in animal products — meat, eggs, dairy); (f) PPI / metformin long-term. Presentation: Megaloblastic anaemia (MCV > 100, hypersegmented neutrophils > 5 lobes) + glossitis + neurological (subacute combined degeneration — demyelination of dorsal columns [loss of vibration + proprioception] + lateral corticospinal tract [spastic paraparesis + hyperreflexia + Babinski] + peripheral neuropathy; dementia; psychiatric). Schilling test (historic). Serum B12 + methylmalonic acid (↑) + homocysteine (↑). Treatment: cyanocobalamin IM or hydroxocobalamin; for dietary can use oral. Folate (B9) absorbed in jejunum; deficiency → megaloblastic anaemia WITHOUT neurological signs; ↑ homocysteine but MMA normal. Sources: leafy greens. Deficiency → neural tube defects (periconceptional folate supplementation 400 μg → prevention). Methotrexate, trimethoprim, pyrimethamine — DHFR inhibitors → folate antagonism. Iron absorbed duodenum + prox jejunum; heme via HCP1, non-heme reduced (Fe3+ → Fe2+) by ascorbate / Dcytb → DMT1 uptake → ferroportin export (hepcidin regulation). Calcium duodenum (calcitriol-dependent, TRPV6 / calbindin); rest of small bowel + colon minor. Fat-soluble vitamins A, D, E, K — small intestine, requires bile salts + pancreatic lipase; stored in liver + adipose. Water-soluble vitamins B complex + C — throughout small intestine; not stored (need regular intake). Bile acids — 95 % reabsorbed in terminal ileum (enterohepatic circulation); ileal resection → bile acid deficiency → steatorrhoea. Short-chain fatty acids (SCFA) from fibre fermentation absorbed in colon.

✔ Correct — A: Salivary α-amylase (ptyalin) from serous cells of parotid + submandibular glands initiates starch digestion — hydrolyses α-1,4 glycosidic bonds of amylose + amylopectin → dextrins + maltose + maltotriose. Active at pH 6.7-7; inactivated by gastric HCl (pH < 4). Digestion continues in small intestine with pancreatic α-amylase → brush-border disaccharidases (maltase, sucrase-isomaltase, lactase, trehalase) → monosaccharides (glucose, galactose, fructose). Saliva: 1-1.5 L/day from parotid (25 %, serous watery, CN IX parasympathetic via otic ganglion), submandibular (70 %, mixed, CN VII chorda tympani via submandibular ganglion), sublingual (5 %, mucous, CN VII), minor glands. Composition: 99 % water + α-amylase + lingual lipase (minor) + mucin + lysozyme + lactoferrin + IgA + kallikrein + sodium / potassium / bicarbonate (buffering; saliva is hypotonic with high K⁺ + HCO₃⁻). pH 6.2-7.6. Functions: mechanical (lubrication, bolus formation, speech), chemical (starch + fat digestion start; buffer neutralises gastric reflux), protective (antimicrobial lysozyme + IgA + lactoferrin + defensins; remineralises teeth — Ca, PO4, F), taste (dissolves tastants). Parasympathetic (CN VII + IX) → copious watery saliva; sympathetic → scant viscous. Xerostomia (dry mouth): Sjögren, radiation, anticholinergics, dehydration; ↑ caries + candidiasis. Digestive enzymes by source: Salivary: α-amylase, lingual lipase. Gastric: pepsin (from pepsinogen via HCl / autocat; cleaves Phe + Tyr + Trp aromatic), gastric lipase (minor). Pancreatic: α-amylase; lipase (needs colipase + bile salts); phospholipase A2; cholesterol esterase; trypsin + chymotrypsin + elastase + carboxypeptidase A & B (endo + exopeptidases); RNase + DNase. Zymogen activation: enterokinase (from duodenal brush border) converts trypsinogen → trypsin → activates others (auto-cascade). Brush-border (duodenum + jejunum): maltase + sucrase + lactase + isomaltase + trehalase; aminopeptidases + dipeptidases; nucleases. Absorption: glucose + galactose (SGLT1 Na⁺-dep into enterocyte, GLUT2 basolat); fructose (GLUT5 apical, GLUT2 basolat); amino acids (Na⁺-dep + independent carriers); short di/tripeptides (PEPT1 H⁺-coupled); fats (micelles → free FA + 2-monoglyceride diffuse → re-esterify → chylomicrons → lacteal → thoracic duct → blood).

✔ Correct — D: Gallbladder (pear-shaped, ~ 50 mL capacity) stores + concentrates bile (5-20 fold — water absorption) between meals. Located on undersurface of liver (segments IV + V). After fatty meal → duodenal I-cells release CCK (cholecystokinin) → gallbladder contraction + sphincter of Oddi relaxation → bile flows via common bile duct into 2nd part of duodenum at ampulla of Vater (joined by main pancreatic duct / duct of Wirsung). Accessory pancreatic duct = Santorini. Liver produces bile (~ 500-800 mL/day) from hepatocytes → bile canaliculi → bile ductules → right + left hepatic ducts → common hepatic duct + cystic duct from gallbladder → common bile duct → duodenum. Bile composition: water (95 %), bile salts (50 % of solids — primary: cholic + chenodeoxycholic; secondary formed by gut bacteria: deoxycholic + lithocholic; conjugated with glycine or taurine → more water-soluble), bilirubin (conjugated, excretion waste), cholesterol + phospholipids (lecithin), electrolytes (HCO₃⁻ rich — pancreatic juice also), IgA. Functions: (1) Emulsify dietary fats (detergent action — hydrophobic + hydrophilic ends form micelles → present triglycerides to lipase); (2) absorb fat-soluble vitamins A, D, E, K; (3) excrete bilirubin, cholesterol, drugs, heavy metals; (4) antimicrobial (bile salts bactericidal). Enterohepatic circulation: 95 % of bile salts reabsorbed in terminal ileum (apical Na⁺-dependent bile acid transporter, ASBT) → portal vein → liver reuse (~ 6-8 cycles per day); only 5 % lost in faeces. Terminal ileum resection → bile salt deficiency → fat malabsorption + steatorrhoea + ADEK deficiency. Gallstones (cholelithiasis) = precipitation of bile components: cholesterol stones (70-80 %, yellow; risk factors 5Fs — Female, Fat, Forty, Fertile, Fair; pregnancy / oestrogen / OCP; rapid weight loss; TPN; ↓ bile acids); pigment stones (black — chronic haemolysis; brown — chronic bile duct infection / parasitic); mixed. Complications: biliary colic, acute cholecystitis (Murphy sign +), cholangitis (Charcot triad — RUQ pain + fever + jaundice; Reynolds pentad adds shock + altered mental), gallstone pancreatitis, gallstone ileus. Tx: cholecystectomy (laparoscopic standard). Bilirubin pathway see Q77. Pancreas: exocrine (acini — digestive zymogens + HCO₃⁻-rich alkaline juice — secretin-stimulated from S cells duodenum) + endocrine (islets of Langerhans — α glucagon, β insulin, δ somatostatin, PP pancreatic polypeptide, ε ghrelin; ~ 1-2 % of pancreas).

✔ Correct — B: Pancreatic juice ~ 1.5 L/day; pH 7.8-8.2 (alkaline) due to high NaHCO₃ (~ 120-140 mmol/L) — neutralises acidic chyme entering duodenum (protects duodenal mucosa + provides optimum pH for pancreatic enzymes). Secreted by ductal cells (via CFTR Cl⁻ channel + Cl⁻/HCO₃⁻ exchanger). Acinar cells secrete enzymes (~ 20 g protein/day). Regulation: Secretin (from S cells in duodenum in response to acid pH < 4.5) → ductal HCO₃⁻ (aqueous bicarbonate-rich secretion). CCK (from I cells in duodenum in response to fatty acids + amino acids) → acinar zymogen release + gallbladder contraction + sphincter of Oddi relaxation + trophic effects. Vagal (CN X) → both. Phases of digestive secretion (same as gastric): cephalic (30 %; sight / smell / taste / thought — vagal); gastric (60 %; distension + peptides — gastrin + local reflexes); intestinal (10 %; CCK + secretin + GIP). Pancreatic enzymes: α-amylase, lipase (+ colipase, phospholipase A2, cholesterol esterase), proteases (trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidase A & B — all zymogens activated via trypsin cascade triggered by duodenal enterokinase), RNase, DNase. Acute pancreatitis = premature trypsin activation + autodigestion; causes mnemonic "I GET SMASHED" (Idiopathic, Gallstones, Ethanol, Trauma, Steroids, Mumps, Autoimmune, Scorpion, Hyperlipidaemia / hypercalcaemia, ERCP, Drugs — sulfa, thiazides, azathioprine, valproate). Presentation: epigastric pain radiating to back + N/V + ↑ amylase (3×) + ↑ lipase (more specific). Grey Turner sign (flank), Cullen sign (periumbilical) = haemorrhagic. Ranson + APACHE scoring. Complications: pseudocyst, necrosis, ARDS, shock, DIC, hypocalcaemia (saponification). Chronic pancreatitis = fibrosis + calcification + exocrine + endocrine insufficiency (steatorrhoea + ADEK deficiency + DM). Alcohol most common (70-80 %). Pancreatic cancer (ductal adenocarcinoma): head most common → obstructive jaundice + Courvoisier sign (palpable non-tender gallbladder); CA 19-9 marker; poor prognosis (Whipple procedure = pancreaticoduodenectomy).

✔ Correct — A: CCK (cholecystokinin) — from I cells in duodenum + jejunum; secreted in response to fatty acids + amino acids + oligopeptides in chyme. Actions: (1) stimulates gallbladder contraction; (2) relaxes sphincter of Oddi → bile flow; (3) stimulates pancreatic acinar enzyme secretion; (4) slows gastric emptying (allows time for digestion); (5) ↑ satiety (CNS effect via vagal afferents); (6) trophic effect on pancreas. Receptors: CCK1 (peripheral), CCK2 (= gastrin receptor; CNS + stomach). Gastrointestinal hormones: Gastrin — G cells (antrum of stomach + duodenum); ↑ by vagal GRP, peptides, stomach distension; ↓ by low pH + somatostatin. Actions: ↑ HCl (via ECL-histamine + direct CCKB on parietal); gastric motility; LES tone; trophic on oxyntic mucosa. Zollinger-Ellison = gastrinoma. Secretin — S cells duodenum; ↑ by acidic pH < 4.5. Actions: ↑ pancreatic + biliary HCO₃⁻ secretion; ↓ gastric acid + motility. First hormone discovered (Bayliss + Starling 1902). GIP (glucose-dependent insulinotropic peptide / gastric inhibitory peptide) — K cells in duodenum + jejunum; ↑ by glucose + fats + amino acids. Actions: ↑ insulin secretion (incretin effect); ↓ gastric motility + acid. GLP-1 (glucagon-like peptide-1) — L cells in ileum + colon; ↑ by nutrients. Actions: ↑ insulin (incretin); ↓ glucagon; ↓ gastric emptying; ↑ satiety. GLP-1 analogues (liraglutide, semaglutide, exenatide, dulaglutide) + DPP-4 inhibitors (sitagliptin, saxagliptin, vildagliptin) for T2DM + obesity. Motilin — M cells duodenum; ↑ migrating motor complex (MMC) during fasting (4 phases, every 90 min; "housekeeper"). Erythromycin = motilin agonist (used for gastroparesis). Somatostatin — D cells throughout GI + delta cells of pancreas; INHIBITS everything (GH, insulin, glucagon, gastrin, CCK, secretin, GI motility, acid). Octreotide = analogue for variceal bleed, carcinoid, acromegaly, secretory diarrhoea. Ghrelin — stomach fundus P/D1 cells; "hunger hormone"; ↑ appetite; rises before meals. Prader-Willi ↑ ghrelin. Leptin — adipocytes; satiety; mutation → obesity. VIP — ENS; ↑ intestinal secretion + smooth muscle relaxation; VIPoma → WDHA / Verner-Morrison (watery diarrhoea + hypokalaemia + achlorhydria). Peptide YY — L cells; ↓ appetite + motility.

✔ Correct — C: Small intestine (~ 6 m; 3 parts — duodenum 25 cm, jejunum 2.5 m, ileum 3.5 m) maximises absorptive surface area (total ~ 200-250 m²) through 3 levels of folding: (1) Plicae circulares (circular folds / valves of Kerckring) — permanent circular mucosal + submucosal folds (prominent in duodenum + jejunum, fewer in ileum) — ↑ area 3×; also slow chyme passage. (2) Villi — finger-like 0.5-1.5 mm mucosal projections (simple columnar epithelium + lamina propria core with capillary network + lacteal [central lymphatic] + smooth muscle fibre); ↑ area 10×. (3) Microvilli (brush border) — cytoplasmic extensions of enterocyte apical membrane (~ 1 μm × 0.1 μm, each cell ~ 3000); ↑ area 20×. Combined ↑ ~ 600× over flat tube. Villi are most prominent in jejunum. Enterocyte lifespan ~ 3-5 days (rapid turnover from crypt stem cells). Villi contain goblet cells (mucus) + enteroendocrine (CCK, secretin, GIP, GLP-1, motilin, serotonin); crypts of Lieberkühn have Paneth cells (defensins + lysozyme + TNF-α — innate immunity), stem cells (Lgr5+). Peyer's patches (submucosal lymphoid aggregates, especially ileum; M cells sample antigens for GALT). Parts of small intestine: Duodenum C-shaped, mostly retroperitoneal; receives bile + pancreatic juice at ampulla of Vater (sphincter of Oddi); Brunner's glands (alkaline mucus in submucosa of duodenum — protect against acid). Jejunum — upper 2/5 of mesenteric small bowel; thicker walls, larger villi, more plicae; main absorption site. Ileum — lower 3/5; Peyer's patches; terminal ileum absorbs B12 + bile salts. Ileocecal valve prevents colonic backflow. Large intestine (~ 1.5 m; caecum + appendix + colon asc / trans / desc / sigmoid + rectum + anus). Features: taeniae coli (3 longitudinal bands), haustra (sacculations), epiploic appendages. Main functions: water + electrolyte absorption (~ 1.5 L/day; dehydrate chyme into faeces), vitamin K + biotin synthesis by bacteria, storage + defaecation. Mucous + goblet cells abundant (no villi); crypts of Lieberkühn present. Gut microbiome ~ 10¹⁴ organisms, ~ 1-2 kg; roles in immunity + metabolism + vitamin synthesis + SCFA (acetate, propionate, butyrate) from fibre fermentation.

✔ Correct — A: Enterokinase (enteropeptidase) = serine protease on brush-border / apical membrane of duodenal enterocytes. Cleaves trypsinogen → trypsin (at Lys6-Ile7 bond, removes N-terminal hexapeptide). Trypsin then triggers zymogen cascade in small intestine: trypsinogen (auto-activation), chymotrypsinogen → chymotrypsin, proelastase → elastase, procarboxypeptidase A/B → carboxypeptidase A/B, prophospholipase A2 → phospholipase A2. This cascade is spatially restricted to intestinal lumen — protects pancreas from self-digestion. Enterokinase deficiency (rare congenital) → protein malabsorption → failure to thrive. Pepsin activation: pepsinogen (from chief cells) activated by HCl + auto-catalytically at gastric pH < 3. Proteases by specificity: Trypsin — cleaves C-side of Lys + Arg (basic). Chymotrypsin — C-side of Phe + Tyr + Trp (aromatic / hydrophobic large). Elastase — C-side of small hydrophobic (Ala + Gly + Ser). Carboxypeptidase A — removes C-terminal aromatic + branched (Phe, Tyr, Trp, Leu, Ile, Val, Met). Carboxypeptidase B — removes C-terminal Arg, Lys. Pepsin — cleaves Phe, Tyr, Trp. Pancreatic self-protection: zymogens (inactive precursors); trypsin inhibitors (SPINK1 / PSTI within pancreas — mutations → hereditary pancreatitis); separation in vesicles / zymogen granules; low Ca²⁺ in acini; cathepsin B degradation. Protein digestion + absorption: dietary protein → gastric pepsin (polypeptides) → pancreatic trypsin / chymotrypsin / elastase (endopeptidases → smaller peptides) → carboxypeptidases (exopeptidases → free amino acids + di/tripeptides) → brush-border aminopeptidases + dipeptidases. Absorption: free AAs via Na⁺-dependent carriers (several — neutral / basic / acidic / imino); di/tripeptides via PEPT1 (H⁺-coupled; also transports β-lactam antibiotics, ACE inhibitors — why these are well absorbed). Aminoaciduria disorders: Hartnup (neutral AA incl. tryptophan → pellagra-like); Cystinuria (COLA — cystine + ornithine + lysine + arginine; kidney stones; hexagonal crystals). Fat digestion: bile-salt emulsification → pancreatic lipase + colipase hydrolyse TG → 2-monoglyceride + 2 free FA; phospholipase A2 → lyso-PL + FA; cholesterol esterase → cholesterol + FA. Products form mixed micelles with bile salts → absorbed by enterocyte → re-esterified → packaged with apoB48, cholesterol, phospholipid into chylomicrons (in ER + Golgi) → exocytosed into lacteals → thoracic duct → left subclavian vein. Short- + medium-chain FAs bypass chylomicrons, absorbed directly into portal blood.

✔ Correct — C: Large intestine functions: (1) Water + electrolyte absorption — ~ 1.5 L fluid enters colon daily, ~ 1.35 L absorbed; Na⁺ absorbed actively via ENaC (aldosterone-sensitive in distal colon) + coupled to K⁺ secretion; Cl⁻ / HCO₃⁻ exchange; water follows passively. (2) Faecal formation + storage — concentrates waste into semisolid; stored in sigmoid + rectum. (3) Bacterial fermentation — undigested CHO (fibre — cellulose + hemicellulose + pectin + resistant starch) + proteins ferment → short-chain fatty acids (acetate, propionate, butyrate — energy source for colonocytes; butyrate has anti-inflammatory + anti-cancer effects; ~ 5-10 % daily calories) + gas (H₂, CO₂, CH₄ — methane producers ~ 1/3 adults). (4) Vitamin synthesis by gut bacteria — vitamin K (menaquinones), biotin (B7), riboflavin (B2), pantothenic acid (B5), folate. (5) Immune function — GALT, dendritic cells, IgA secretion; tolerance to commensals. (6) Defaecation — reflex triggered by rectal distension (gastrocolic reflex → peristalsis); involuntary internal anal sphincter (smooth muscle, sympathetic contraction / parasympathetic relaxation) + voluntary external sphincter (skeletal, pudendal nerve S2-S4). Parts of large intestine: caecum (blind pouch, attached appendix — lymphoid, "thoracic GI organ in abdomen"), ascending + transverse + descending + sigmoid colon, rectum (stores faeces, has 3 transverse folds — valves of Houston), anal canal (ends at anus; pectinate / dentate line divides upper [endoderm, insensate, autonomic, visceral pain] from lower [ectoderm, somatic sensation via pudendal nerve]). Colon has: taeniae coli (3 longitudinal bands — converge at appendix base), haustra (sacculations), epiploic / omental appendages (fatty tags). Mass movements 3-4/day (gastrocolic reflex). Transit time ~ 24-48 h. Appendix = lymphoid organ; acute appendicitis classic surgical emergency (McBurney point tenderness, rebound, Rovsing, psoas, obturator signs; tx laparoscopic appendectomy). Diseases: IBD = Crohn's (transmural, skip lesions, any GI, cobblestone, granulomas, fistulae, strictures; tx TNF-α mAb infliximab/adalimumab, ustekinumab, vedolizumab, 5-ASA, steroids, immunosuppressives) vs UC (mucosal, continuous, rectum → proximal, pseudopolyps, crypt abscesses, lead-pipe colon, ↑ CRC risk; tx similar + colectomy curative). IBS (functional, Rome IV). Colon cancer (adenoma → carcinoma sequence; APC / KRAS / TP53 / SMAD4; screen 45+ via colonoscopy q10y; Lynch / FAP hereditary). Diverticulosis (elderly, low fibre, sigmoid).

✔ Correct — D: Urea synthesised in liver (hepatocyte) via urea cycle (Krebs-Henseleit cycle, 1932) to detoxify ammonia (NH₃) from amino acid catabolism. Reactions span mitochondria + cytosol: (1) Carbamoyl phosphate synthetase I (CPS-I, mitochondrial; rate-limiting; N-acetylglutamate NAG activator): NH₃ + HCO₃⁻ + 2 ATP → carbamoyl phosphate. (2) Ornithine transcarbamylase (OTC, mitochondrial): carbamoyl phosphate + ornithine → citrulline. (3) Citrulline exits mitochondria. (4) Argininosuccinate synthetase: citrulline + aspartate + ATP → argininosuccinate + AMP + PPi. (5) Argininosuccinate lyase: argininosuccinate → arginine + fumarate. (6) Arginase: arginine → urea + ornithine (regenerates ornithine). Net: 2 NH₃ (one from NH₄⁺, one from aspartate) + HCO₃⁻ + 3 ATP → urea + fumarate. 4 ATP consumed (3 ATP → 2 ADP + 2 Pi + AMP + PPi; AMP → 2 ATP). Urea released into blood → excreted by kidneys (normal BUN 7-20 mg/dL = 2.5-7 mmol/L). Urea cycle disorders (hyperammonemia): OTC deficiency = most common + X-linked (others autosomal recessive); presents with protein intolerance, vomiting, encephalopathy, hyperammonaemia, respiratory alkalosis, orotic aciduria in OTC (↑ orotic acid due to carbamoyl phosphate shunt to pyrimidine synthesis). Tx: low protein, lactulose, sodium benzoate + phenylacetate (bind amino acids for excretion), arginine / citrulline supplementation, liver transplant. Ammonia transport to liver via alanine (glucose-alanine cycle from muscle) + glutamine (from most tissues, glutamine synthetase uses NH3 + glutamate → glutamine; released to kidney + liver; glutaminase releases NH3 for urea / excretion). Kidney also excretes NH3/NH4+ as a buffer in acid-base handling (NH4+ excretion ↑ in metabolic acidosis). Hepatic encephalopathy (cirrhosis): ↑ NH3 crosses BBB, astrocyte glutamine accumulation, osmotic cerebral oedema; tx lactulose (acidifies colon → NH4+ trapped + excreted) + rifaximin (↓ urease-producing gut bacteria). Nitrogen balance: +ve (growth, pregnancy); -ve (starvation, trauma, burn, infection, old age). Protein turnover ~ 300 g/day; half-lives vary (ornithine decarboxylase ~ 10 min; albumin 20 days; collagen months). Other liver functions: carbohydrate metabolism (glycogen storage, gluconeogenesis, glycolysis), lipid metabolism (β-oxidation, ketogenesis, cholesterol + lipoprotein synthesis), protein synthesis (albumin, globulins except gamma, clotting factors all except VIII), bilirubin conjugation, drug metabolism (CYP450), bile synthesis, Kupffer cells (RES), storage (vit A, D, B12, Fe, Cu, glycogen).

✔ Correct — C: Fat-soluble vitamins: A, D, E, K (mnemonic "All Dogs Eat Kebabs"). Absorbed with dietary fat + bile salts in small intestine; stored in liver + adipose tissue; can accumulate → toxicity. Vitamin A (retinol) — sources: liver, fish oil, dairy, β-carotene (provitamin A in orange / green vegetables). Functions: vision (11-cis-retinal forms rhodopsin with opsin), epithelial growth + differentiation, immunity, reproduction, antioxidant. Deficiency: night blindness, xerophthalmia, Bitot spots, keratomalacia, ↑ infections; toxicity (acute — pseudotumour cerebri; chronic — hepatotoxicity, bone pain, birth defects — teratogenic in pregnancy — isotretinoin warning). RDA ~ 700 μg F / 900 μg M. Vitamin D (cholecalciferol D3 / ergocalciferol D2) — sources: skin synthesis from 7-dehydrocholesterol via UVB; fatty fish, fortified dairy, egg yolk. Metabolism: D3 → liver 25-hydroxylation (25-OH-D = storage form / best status marker) → kidney 1α-hydroxylation (1,25-(OH)2-D = calcitriol, active; PTH ↑ 1α-hydroxylase). Functions: ↑ intestinal Ca²⁺ + PO₄³⁻ absorption, ↑ bone mineralisation, renal reabsorption, immune modulation. Deficiency: rickets (children — bowed legs, rachitic rosary, craniotabes, delayed fontanelle closure, Harrison sulcus); osteomalacia (adults — bone pain, pseudofractures / Looser zones, hypocalcaemia / hypophosphataemia); ↑ risk of falls, cancer, autoimmune. Toxicity: hypercalcaemia → stones / bones / moans / groans. RDA 600 IU (15 μg); 800+ IU for elderly. Vitamin E (tocopherol, α-tocopherol most active) — sources: vegetable oils, nuts, seeds, green leafy. Antioxidant (free-radical scavenger; protects membranes). Deficiency rare: haemolytic anaemia in preterm infants, peripheral neuropathy, ataxia (posterior column demyelination), retinopathy — seen in abetalipoproteinaemia + CF + cholestatic liver disease. Toxicity uncommon but anticoagulant effect in high doses. Vitamin K (phylloquinone K1 / menaquinone K2 / menadione K3) — sources: green leafy, gut bacteria (K2), fermented foods. Cofactor for γ-glutamyl carboxylase → activates factors II, VII, IX, X + Protein C + S (γ-carboxylation of Glu → Gla — Ca²⁺ + PL binding). Deficiency: haemorrhagic disease of newborn (neonatal vit K IM routine); malabsorption; antibiotic use; warfarin-induced. Measured by PT / INR. Water-soluble vitamins: B complex + C. B1 (thiamine — TPP coenzyme for PDH, αKG DH, transketolase; def → beriberi [wet + dry], Wernicke [CAN — confusion, ataxia, nystagmus] / Korsakoff [memory + confabulation]; alcoholics); B2 (riboflavin — FAD, FMN; def → cheilosis, glossitis); B3 (niacin — NAD, NADP; def → pellagra 4D — diarrhoea, dermatitis, dementia, death; isoniazid, Hartnup); B5 (pantothenic — CoA); B6 (pyridoxine — transamination, aa metabolism, decarboxylation; def → sideroblastic anaemia, peripheral neuropathy; excess → peripheral neuropathy); B7 (biotin — carboxylations; def rare, raw egg avidin); B9 (folate — THF for DNA synthesis; def → megaloblastic anaemia, neural tube defects); B12 (cobalamin — methionine synthase, methylmalonyl-CoA mutase; def → megaloblastic + neurological); C (ascorbic acid — antioxidant, collagen hydroxylation, iron absorption, carnitine + NE synthesis; def → scurvy — bleeding gums, poor wound healing, corkscrew hair, petechiae, perifollicular haemorrhages).

✔ Correct — B: Enteric nervous system (ENS) = "second brain"; ~ 100-500 million neurons (more than spinal cord); extensive intrinsic innervation of GIT from oesophagus to anus. Two major plexuses: (1) Myenteric plexus (Auerbach's) — between longitudinal + circular smooth muscle layers; primarily controls GI MOTILITY (peristalsis + segmentation + tone). (2) Submucosal plexus (Meissner's) — in submucosa; primarily controls SECRETION + local blood flow + mucosal function. ENS works autonomously (peristalsis persists if extrinsic nerves cut) but modulated by autonomic NS: Parasympathetic (vagus CN X to splenic flexure; S2-S4 pelvic splanchnics thereafter) — ↑ motility + secretion via ACh on M3 + NANC (non-adrenergic non-cholinergic) transmitters (VIP, NO — relaxation). Sympathetic (T1-L2 → coeliac / superior mesenteric / inferior mesenteric ganglia) — ↓ motility + secretion via α2 on enteric neurons (except secretion-inhibitory), α1 on sphincters (contract). Interstitial cells of Cajal (ICC) — pacemaker cells between smooth muscle fibres; generate slow waves (basal electrical rhythm — 3/min stomach, 12/min duodenum, 8/min ileum, 3/min colon) → superimposed spike potentials cause contraction. Loss of ICC → gastroparesis, chronic intestinal pseudo-obstruction. Types of GI motility: (1) Peristalsis — wave of circular muscle contraction behind bolus + relaxation ahead → propulsion (law of intestine); (2) Segmentation — alternating contractions of circular muscle at intervals → mix chyme with digestive juices (main in small intestine between meals); (3) Migrating motor complex (MMC) — fasting "housekeeper" — waves of activity every 90-120 min moving debris from stomach to ileum; triggered by motilin. (4) Mass movements — 3-4× /day in colon (gastrocolic reflex after meals; responsible for defaecation urge). (5) Haustrations — segmentation-like in colon. Swallowing — 3 phases: oral (voluntary — tongue propels bolus); pharyngeal (reflex — swallowing centre medulla; soft palate elevates, epiglottis closes, LES relaxes); oesophageal (primary peristalsis + secondary). Upper oesophageal sphincter (UES) = cricopharyngeus (skeletal). Lower oesophageal sphincter (LES) = physiological; ↓ in GERD, hiatus hernia; ↑ in achalasia (loss of myenteric neurons — birds-beak on barium swallow, ↑ LES pressure, aperistalsis; tx CCB + nitrates + pneumatic dilatation + Heller myotomy + botulinum). Defaecation reflex — rectal distension → parasympathetic (S2-S4 pelvic splanchnic) → rectal contraction + internal anal sphincter relaxation; voluntary control of external sphincter (pudendal nerve); Valsalva aids. Diseases of GI motility: achalasia, GERD, gastroparesis (diabetes; prokinetic metoclopramide D2 antagonist, erythromycin motilin agonist, domperidone peripheral D2), IBS, constipation / diarrhoea, Hirschsprung disease (congenital absence of ganglion cells in distal colon — failure of craniocaudal neural crest migration → functional obstruction + megacolon; RET mutation).