AN67.1-3 | Muscle histology — Gate Quiz

Correct. Cardiac muscle is identified by: (1) Cross-striations (like skeletal); (2) Central 1–2 nuclei (unlike skeletal peripheral); (3) Branching fibres (unlike skeletal cylindrical); (4) INTERCALATED DISCS — the pathognomonic feature — dark transverse bands at the junctions between adjacent cardiomyocytes (contain fascia adherens for mechanical coupling + gap junctions for electrical coupling).

Muscle identification table: Skeletal = long cylindrical fibres, PERIPHERAL MULTIPLE nuclei, striated, no branching, no intercalated discs. Cardiac = branching, CENTRAL 1-2 nuclei, striated, INTERCALATED DISCS. Smooth = spindle-shaped, CENTRAL SINGLE nucleus, NO striations. Exam tip: The single most distinguishing feature of cardiac muscle = intercalated discs. In MI histology slides: ghost fibres (hypereosinophilic, lost nuclei, sarcomere ghosting) = ischaemic necrosis.

Cardiac muscle is the answer. The intercalated disc is the diagnostic feature — not seen in skeletal or smooth muscle. Intercalated disc components: transverse portion = fascia adherens (desmosome-like, N-cadherin) + desmosome; longitudinal portion = gap junctions (connexin 43). The gap junctions allow electrical coupling → functional syncytium → coordinated contraction of the entire myocardium.

Correct. Smooth muscle in transverse section appears as closely packed circular profiles of varying sizes — this is because spindle-shaped cells are longest in the middle (where the nucleus is) and taper at both ends. Cells cut through their widest part show a circular profile with a nucleus; cells cut through their tips appear as small circles without nuclei. No striations visible.

Smooth muscle cross-section identification: varying circle sizes (spindle cells) + no striations + some cells show central nuclei while others don't (depends on level of cut). Longitudinal section: elongated cells, central elongated (cigar-shaped) nuclei, no striations. Clinical: intestinal smooth muscle = 2 layers in muscularis externa (inner circular + outer longitudinal) → peristalsis. Myometrium (uterine smooth muscle): hypertrophies during pregnancy (progesterone → growth); oxytocin → smooth muscle contraction (labour). Hypertension → vascular smooth muscle hypertrophy.

Smooth muscle in transverse section is the answer. The varying circle sizes are a characteristic feature of smooth muscle cross-sections due to the spindle shape of individual cells. Skeletal muscle in cross-section shows polygonal profiles all of roughly similar size (large diameter fibres), with peripheral nuclei. Cardiac muscle cross-section shows branching profiles with central nuclei and intercalated discs visible.

Correct. Type I (slow oxidative, red) fibres are characterised by: slow contraction speed, high fatigue resistance, reliance on aerobic/oxidative metabolism, abundant mitochondria, high myoglobin content (gives red colour), and good blood supply. These are ideal for endurance activities (marathon, postural muscles like soleus). Endurance training increases the proportion of type I fibres.

Muscle fibre type comparison: Type I (Slow, Red): slow myosin ATPase, many mitochondria, high myoglobin, oxidative enzymes (SDH/NADH-TR staining strong), resistant to fatigue → postural muscles (soleus, paraspinal), endurance athletes. Type IIb (Fast, White): fast myosin ATPase, few mitochondria, low myoglobin, glycolytic enzymes, fatigues quickly → explosive movement (gastrocnemius, eye muscles). Type IIa (Fast, Intermediate): mixed. Myopathy biopsy: fibre type grouping (reinnervation) vs random atrophy (primary myopathy) vs inflammatory infiltrate (myositis).

Type I (slow oxidative) fibres are the answer for endurance. Type IIb (fast glycolytic) = white, few mitochondria, fatigue rapidly; used in sprinting/explosive bursts (100m dash, powerlifting). Type I = red (high myoglobin), many mitochondria, fatigue-resistant; used in posture and endurance. Endurance training → type IIb → type IIa conversion. Sprint training → type IIb hypertrophy. Clinical: disuse atrophy (bed rest, immobilisation) → preferential type II atrophy first. Denervation atrophy = angular atrophy of all fibres in a motor unit.

Correct. The A-band spans the full length of the MYOSIN (thick) filaments. Since myosin filaments do not change length during contraction, the A-band also remains constant. In contrast: I-band shortens (only actin, and actin slides INTO the A-band); H-zone shortens (actin overlaps further until H-zone disappears); sarcomere overall shortens. The Z-lines move closer together as the sarcomere shortens.

Sarcomere bands during contraction: A-band = Always the same (A = Always). I-band = I-band is Inversely proportional (shortens). H-zone = Halves and disappears at full contraction. Z-lines = Zip together (move closer). Total sarcomere shortens. Mnemonic: "A bands Are the same, I bands and H zones Implode and disappear, Z lines Zoom together." Contraction band necrosis in MI = hypercontracted sarcomeres (eosinophilic transverse bands) indicating reperfusion injury after ischaemia.

The A-band is constant in length. Sliding filament theory: thin (actin) filaments slide TOWARD the M-line between thick (myosin) filaments during contraction. What changes: I-band SHORTENS (actin pulls toward M-line); H-zone SHORTENS and disappears (actin reaches M-line); sarcomere SHORTENS (Z-lines move closer). What stays same: A-band (full length of myosin = unchanged); myosin filaments themselves. Sarcomere shortening = actin overlap increases, not filaments shortening.

Correct. In skeletal muscle, T-tubules run at the A-I junction (where the A-band and I-band meet), so there are TWO T-tubules per sarcomere. This position flanked by two terminal cisternae of the SR forms the TRIAD. In cardiac muscle, T-tubules are at the Z-LINE (one per sarcomere) and form a DYAD with ONE flanking SR cisterna.

T-tubule/SR relationships: Skeletal muscle: A-I junction, 2 T-tubules/sarcomere, TRIAD = T-tubule + 2 SR cisternae. Cardiac muscle: Z-line, 1 T-tubule/sarcomere (but wider/longer), DYAD = T-tubule + 1 SR cisterna. DHPR (dihydropyridine receptor, L-type Ca²⁺ channel) = voltage sensor in T-tubule. RyR1 (skeletal) / RyR2 (cardiac) = Ca²⁺ release channel in SR. Coupling: skeletal = mechanical coupling (DHPR physically linked to RyR1); cardiac = Ca²⁺-induced Ca²⁺ release (DHPR allows Ca²⁺ in → triggers RyR2). Malignant hyperthermia (halothane → RyR1 mutation → uncontrolled Ca²⁺ release → hyperthermia, muscle rigidity).

T-tubules in skeletal muscle = A-I junction × 2 per sarcomere → TRIAD (T-tubule flanked by two terminal cisternae). In cardiac muscle = Z-line × 1 per sarcomere → DYAD (T-tubule + one SR cisterna). T-tubules transmit the action potential (from surface sarcolemma to fibre interior) rapidly, ensuring simultaneous contraction throughout the fibre width. The terminal cisternae store Ca²⁺; RyR1 (skeletal) and RyR2 (cardiac) are the Ca²⁺ release channels of the SR.

Correct. Cardiomyocytes are terminally differentiated — they withdraw from the cell cycle after birth. Unlike skeletal muscle (which has resident satellite cells for regeneration) and smooth muscle (which retains limited proliferative capacity), the heart has no significant resident stem cell population for cardiomyocyte replacement. Damaged cardiomyocytes → fibrotic scar (non-contractile).

Regenerative capacity of muscle: Skeletal > Smooth > Cardiac. Skeletal: satellite cells (Pax7+, MyoD+) under basal lamina; activated by injury → proliferate → myoblasts → fuse → new fibre (central nucleus transiently). Smooth: can proliferate from smooth muscle cells themselves or pericytes. Cardiac: essentially none; ~1% annual turnover (too slow to compensate for large infarcts). Post-MI scar: fibrous connective tissue (passive expansion → ventricular aneurysm risk); papillary muscle infarction → mitral regurgitation.

Cardiomyocytes are terminally differentiated and essentially cannot divide. Unlike skeletal muscle (satellite cells allow regeneration, limited but present) and smooth muscle (can regenerate from pericytes and smooth muscle cells), cardiac muscle lacks a stem cell population. Post-MI: dead cardiomyocytes → replaced by fibrous scar (collagen from fibroblasts). This scar does not contract → reduced EF → heart failure. Current research: induced pluripotent stem cells (iPSCs), direct cardiac reprogramming to regenerate heart muscle.

Correct. Dystrophin acts as a "mechanical shock absorber" linking the intracellular actin cytoskeleton to the extracellular matrix (via β-dystroglycan → laminin in basal lamina). This coupling distributes the mechanical stress of contraction across the sarcolemma, preventing membrane tears. Without dystrophin (DMD), the sarcolemma ruptures with each contraction → Ca²⁺ floods in → proteases activated → fibre necrosis.

Dystrophin-associated protein complex (DAPC): Dystrophin (F-actin inside) → β-dystroglycan (transmembrane) → α-dystroglycan (extracellular) → laminin-2 (basal lamina). Sarcoglycans (α,β,γ,δ) also in DAPC — LGMD (limb-girdle muscular dystrophy) results from sarcoglycan mutations. DMD gene on Xp21 (X-linked recessive) → 1/3500 live male births; frameshift deletion → no dystrophin. Becker = in-frame deletion → reduced/truncated dystrophin → onset 5–15 years, ambulatory to 20s–30s. Diagnosis: CK (markedly elevated), EMG (myopathic), muscle biopsy (dystrophin absent on immunostaining), genetic testing (deletion on multiplex PCR).

Dystrophin = mechanical stabiliser of the sarcolemma. DMD: dystrophin absent → sarcolemma tears during contraction → uncontrolled Ca²⁺ influx → calpain (Ca²⁺-activated protease) activation → myofibril degradation → fibre necrosis. CK leaks into blood → serum CK markedly elevated (10,000–100,000 U/L). Becker MD = truncated dystrophin (some function retained) → milder phenotype. Utrophin (dystrophin homologue) upregulation is one therapeutic strategy in DMD.

Correct. Endomysium = fine reticular fibre-based sheath directly around each individual muscle fibre (cell). Contains a dense capillary network (one capillary per fibre for O₂ delivery) and motor nerve terminals (neuromuscular junctions). Perimysium surrounds fascicles (groups of fibres). Epimysium surrounds the entire muscle.

Skeletal muscle organisation: Individual fibre → Fascicle → Whole muscle. CT sheaths: Endomysium (reticular fibres) → around each fibre; contains NMJ, satellite cells, capillaries. Perimysium → around fascicles; contains intramuscular nerves and vessels; injection site for IM injections. Epimysium → around whole muscle; merges with tendon. In submandibular gland and other glands: acinus = structural unit; perimysium equivalent = perilobular CT. Note: connective tissue sheaths are continuous and merge at the tendon → force transmission from muscle to bone.

Endomysium is the innermost sheath (around each individual fibre). Mnemonic: "E-P-E from inside out" = Endo (individual fibre) → Peri (fascicle) → Epi (whole muscle). Endomysium = mainly type III collagen (reticular fibres) → fine, flexible sheath; contains satellite cells (muscle stem cells) between the endomysium and sarcolemma. Perimysium = type I collagen; bundles fascicles; contains larger blood vessels. Epimysium = dense irregular CT; merges with tendon (dense regular CT) at the musculotendinous junction.

Correct. In skeletal muscle, E-C coupling is a MECHANICAL process: DHPR (voltage-gated L-type Ca²⁺ channel in T-tubule) acts as a voltage sensor. When the T-tubule is depolarised, DHPR undergoes conformational change → DIRECTLY activates RyR1 (via physical protein-protein interaction, not via Ca²⁺). This is direct mechanical coupling. Contrast: cardiac muscle uses CICR (Ca²⁺ entry through DHPR triggers RyR2 → Ca²⁺-induced Ca²⁺ release).

E-C coupling comparison: Skeletal (mechanical): AP → T-tubule DHPR → conformational change → directly activates RyR1 → Ca²⁺ released. Cardiac (CICR): AP → T-tubule DHPR → small Ca²⁺ influx → triggers RyR2 → large Ca²⁺ release. Both: Ca²⁺ + troponin C → tropomyosin moves → actin-myosin cross-bridge. SERCA pump returns Ca²⁺ to SR (relaxation). Cardiac muscle also has NCX (Na-Ca exchanger) for Ca²⁺ removal. Digitalis (cardiac glycoside): inhibits Na-K ATPase → Na accumulates → Ca²⁺ extrusion via NCX reduced → more intracellular Ca²⁺ → stronger contraction (positive inotrope).

Skeletal muscle = MECHANICAL coupling (DHPR physically linked to RyR1; no Ca²⁺ needed for triggering). Cardiac muscle = Ca²⁺-induced Ca²⁺ release (DHPR allows Ca²⁺ in → triggers RyR2 → large Ca²⁺ release). Evidence: skeletal muscle can contract without extracellular Ca²⁺; cardiac muscle cannot. Dantrolene blocks RyR1 → reduces SR Ca²⁺ release → reduces muscle contractility → treats malignant hyperthermia (also used in spasticity, rhabdomyolysis). Malignant hyperthermia: RyR1 mutation (sensitised to halothane) → massive Ca²⁺ release → sustained contraction → heat generation → hyperthermia (can be fatal if untreated).

Correct. Gap junctions (in the lateral portions of intercalated discs; composed of connexin 43 in ventricular cardiomyocytes) are the electrical coupling junction. Connexons (half-channels) on adjacent cells align → full channel → allows ions (Na⁺, K⁺, Ca²⁺) to flow directly between cytoplasms → action potential propagates from cell to cell without crossing a synapse → "functional syncytium."

Intercalated disc components: Fascia adherens (large, most of transverse part) = N-cadherin + actin = mechanical coupling during contraction (like an adherens junction). Desmosome = desmoplakin + intermediate filaments = prevents pulling apart during contraction. Gap junction (small junctions at step/lateral part) = connexin 43 = electrical coupling → AP propagates cell-to-cell. ARVC (arrhythmogenic right ventricular cardiomyopathy): mutations in desmosomal proteins (desmoplakin, plakophilin-2, desmoglein-2) → fibro-fatty replacement of RV myocardium → ventricular arrhythmias → sudden cardiac death in young athletes.

Gap junctions (connexin 43) are the electrical coupling component of the intercalated disc. The intercalated disc has three components: (1) Fascia adherens (transverse portion) = mechanical adhesion (N-cadherin, links to actin filaments inside); (2) Desmosome (transverse and longitudinal) = strong mechanical junction (desmoplakin, links to intermediate filaments); (3) Gap junction (longitudinal step portions) = electrical + metabolic coupling (connexin 43). Loss of gap junctions → arrhythmias. Loss of desmoplakin/plakophilin → ARVC (arrhythmogenic right ventricular cardiomyopathy).