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AN68.1-3 | Nervous tissue histology — Gate Quiz
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A histology section shows clusters of large round cells of varying sizes. Each cell has a large pale nucleus with a prominent nucleolus, and a surrounding ring (capsule) of small flattened cells. Between the clusters are myelinated nerve fibres and connective tissue. This section is most likely from:
Correct. A dorsal root (spinal) ganglion contains pseudounipolar sensory neurons — round cells with large pale nuclei and prominent nucleoli. Each neuron is completely surrounded by a ring of satellite (capsule) cells. Between neurons are myelinated nerve fibres and connective tissue. This is the classic "ganglionic" appearance.
Ganglia types and histology: Dorsal root (spinal) ganglion = pseudounipolar neurons (round, varying sizes, prominent nucleolus) + satellite cells (complete capsule) + myelinated fibres. Autonomic ganglion = multipolar neurons (irregular with dendrites) + satellite cells (less complete) + unmyelinated post-ganglionic fibres. Cranial nerve sensory ganglia (trigeminal, geniculate, spiral) = similar to DRG (pseudounipolar). Clinical: Herpes zoster = VZV reactivation in DRG → travels along sensory nerve → dermatomal vesicular rash (shingles) — common in India in immunocompromised patients.
Dorsal root ganglion is the answer. Identify ganglia by: (1) Round neuron cell bodies (not the elongated shape of fibre tracts); (2) Satellite cell capsule around each neuron; (3) Mixed population of neurons (varying sizes); (4) Connective tissue framework with nerve fibres. Compare: Spinal cord anterior horn = multipolar neurons embedded in neuropil (not as round, no satellite cell capsule, many glial cells around, no connective tissue). Autonomic ganglion = multipolar neurons, less complete satellite cell investment.
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On a cross-section of the sciatic nerve stained with H&E, you identify multiple fascicles. Each fascicle is surrounded by a concentric layer of flattened cells with tight junctions forming the blood-nerve barrier. This layer surrounding the fascicle is the:
Correct. Perineurium = concentric layers of flattened perineurial cells with tight junctions between them → creates the blood-nerve barrier (selectively restricts access to the endoneurial space). Surrounds each fascicle. It is the STRONGEST structural component of a nerve (used in nerve repair — perineurial sutures). Epineurium = outermost, dense irregular CT around whole nerve. Endoneurium = fine reticular fibres around each individual axon.
Peripheral nerve connective tissue sheaths: Endoneurium (around each axon): type III collagen + fibroblasts; continuation of CNS meninges-equivalent; Schwann cell basal lamina is part of this. Perineurium (around fascicle): multi-layered, flattened perineurial cells + tight junctions = blood-nerve barrier; metabolic/ionic homeostasis of endoneurial space. Epineurium (around whole nerve): dense irregular CT; contains vasa nervorum (blood supply to the nerve itself); adipose tissue cushions nerve. Clinical note: carpal tunnel syndrome = compression of median nerve in carpal tunnel → perineurial oedema → axonal compression → tingling and weakness in hand; median nerve territory. Common in women doing repetitive hand work in India.
Perineurium is the answer. The perineurium forms the blood-nerve barrier via tight junctions between perineurial cells (similar role to the blood-brain barrier astrocytes in the CNS). Fascicle = bundle of axons within the perineurium. Clinical: perineurial invasion by cancer (perineural invasion) = a sign of aggressive tumour behaviour in salivary gland cancers, prostate cancer, pancreatic cancer — indicates spread along nerve sheaths. Leprosy: M. leprae invades the perineurium and Schwann cells → disrupts blood-nerve barrier → nerve damage.
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In a large multipolar motor neuron (anterior horn cell), Nissl substance (basophilic granules of rough ER + ribosomes) is found in all of the following locations EXCEPT:
Correct. Nissl substance is absent from the axon hillock and the axon. This is the histological basis for the axon hillock appearing pale/clear in Nissl-stained sections. The axon cannot synthesise proteins because it lacks ribosomes (no RER). All proteins used in the axon must be synthesised in the soma and transported down the axon (anterograde axonal transport). Dendrites DO contain Nissl substance (RER + ribosomes) and can synthesise proteins locally.
Nissl substance distribution: Soma = YES (most concentrated). Dendrites = YES (RER + free ribosomes; local protein synthesis for synaptic plasticity). Axon hillock = NO (Nissl-free zone on Nissl stain = pale hillock). Axon = NO (no ribosomes at all). Axon terminal = NO. Chromatolysis = dispersion of Nissl substance + swelling of soma + peripheral displacement of nucleus = retrograde cell reaction to axonal injury; indicates attempt at regeneration. Severe injury → chromatolysis is irreversible → neuronal death.
Axon hillock and axon do NOT contain Nissl substance. The axon is the one cellular compartment without protein synthesis machinery. This is why axonal transport is so critical — all membrane proteins, enzymes, cytoskeletal proteins, and synaptic vesicle proteins must travel from the soma. Chromatolysis (dissolution of Nissl substance in the soma + cell body swelling + nucleus displacement) occurs after axonal injury — the soma "gears up" for regeneration by dispersing its RER.
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Organophosphate pesticide poisoning (very common in India — a major cause of suicidal and accidental poisoning in rural areas) inhibits acetylcholinesterase at cholinergic synapses. Acetylcholine accumulates in the synaptic cleft, causing sustained activation of post-synaptic receptors. The immediate trigger for acetylcholine release from the pre-synaptic terminal is:
Correct. At a chemical synapse: action potential arrives at the axon terminal → depolarises the terminal membrane → voltage-gated Ca²⁺ channels open → Ca²⁺ influx → Ca²⁺ binds to synaptotagmin (SNARE complex calcium sensor) → SNARE complex (synaptobrevin + SNAP25 + syntaxin) mediates vesicle fusion with pre-synaptic membrane → acetylcholine released into synaptic cleft.
NT release mechanism: AP → VGCC open → Ca²⁺ influx → synaptotagmin activated → SNARE (synaptobrevin/vesicle-associated + SNAP25 + syntaxin/target membrane) form a zipper → vesicle fusion → NT exocytosis. Botulinum toxin: cleaves SNARE proteins (BoNT/A cleaves SNAP25, BoNT/B cleaves synaptobrevin) → blocks NT release → flaccid paralysis (descending, unlike tetanus). Therapeutic use in India: cosmetic, cervical dystonia, spasticity (cerebral palsy), hyperhidrosis. Tetanus toxin: reaches CNS by retrograde transport → blocks glycine/GABA release from inhibitory interneurons → spastic paralysis (sustained contraction), trismus (lockjaw).
Ca²⁺ influx is the trigger for neurotransmitter release. Voltage-gated Ca²⁺ channels (P/Q-type at NMJ, N-type at most synapses) open when the terminal is depolarised by the arriving AP → Ca²⁺ concentration inside rises ~100-fold → activates synaptotagmin (the Ca²⁺ sensor) → SNARE complex zippers → synaptic vesicle fuses with pre-synaptic membrane → NT released by exocytosis. Lambert-Eaton myasthenic syndrome (LEMS) = antibodies against pre-synaptic voltage-gated Ca²⁺ channels → reduced NT release → proximal muscle weakness (common paraneoplastic syndrome with SCLC).
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A 35-year-old man is bitten by a stray dog on his right foot. He does not receive anti-rabies prophylaxis. Six weeks later, he develops rabies encephalitis. The rabies virus travels from the wound site (right foot skin) to the spinal cord and brain via axonal transport in sensory and motor nerve fibres. This type of axonal transport is:
Correct. Retrograde axonal transport (from axon terminal back to cell body) uses dynein as the motor protein, travelling toward the minus end of microtubules (at the soma). Speed: 150–200 mm/day (fast retrograde). Neurotrophic viruses (rabies, herpes simplex, poliovirus, tetanus toxin) hijack retrograde transport to travel to the CNS. This is why rabies from a foot bite takes weeks to cause encephalitis (long journey up the sciatic nerve to the spinal cord).
Axonal transport summary: ANTEROGRADE (soma → terminal): Fast (kinesin, 200–400 mm/day) → synaptic vesicles, mitochondria, membrane proteins, lipids. Slow (1–4 mm/day) → neurofilaments, tubulin, cytosolic enzymes. RETROGRADE (terminal → soma): Fast (dynein, 150–200 mm/day) → endosomes, autophagosomes, NGF-receptor complexes, viruses (rabies, HSV, polio), toxins (tetanus, botulinum retrograde partial). Axonal transport failure: Alzheimer's (tau hyperphosphorylation disrupts microtubule tracks → impaired transport → synaptic failure). Amyloid precursor protein (APP) accumulates in swollen axons (spheroids) when transport is disrupted.
Retrograde transport (dynein) is correct for viral transport. Anterograde = soma to terminal (kinesin). Retrograde = terminal to soma (dynein). Viruses that use retrograde transport: rabies (sensory and motor nerve endings → DRG/ventral horn → brainstem), herpes simplex (skin/mucosa → DRG → latency), poliovirus (motor end plate → anterior horn cell → poliomyelitis), tetanus toxin (NMJ → anterior horn → brainstem inhibitory interneurons). Speed: fast retrograde = 150–200 mm/day (vesicle-associated cargoes). Slow retrograde = lysosomal products and signalling molecules.
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In Guillain-Barré syndrome (GBS, AIDP subtype), autoantibodies attack the myelin of peripheral nerves. The cells responsible for forming peripheral nerve myelin (and therefore the target of the immune attack) are:
Correct. Schwann cells form the myelin sheath of peripheral nervous system axons. One Schwann cell myelinates ONE internodal segment of ONE axon (unlike oligodendrocytes, which myelinate up to 50 axon segments). In GBS (AIDP), molecular mimicry (Campylobacter jejuni antigens mimic gangliosides on Schwann cell myelin) → IgG autoantibodies + complement → demyelination → slowed conduction → weakness.
CNS vs PNS myelination: CNS (oligodendrocytes): one cell wraps multiple axons (up to 50); myelin proteins = MBP, PLP, CNPase; no basement lamina around oligodendrocytes; MS attacks CNS myelin. PNS (Schwann cells): one cell wraps ONE internode of ONE axon; myelin proteins = MBP, P0 (most abundant PNS myelin protein), PMP22; Schwann cells have their own basal lamina. Basal lamina remnant = key for PNS regeneration (Bands of Büngner scaffold). GBS treatment: IVIG (neutralises autoantibodies) or plasmapheresis (removes autoantibodies). Prognosis: most recover over weeks to months.
Schwann cells (PNS) is the answer. Oligodendrocytes (CNS): myelinate multiple axons (up to 50); target in MS (multiple sclerosis) and PML (JC virus). Schwann cells (PNS): one cell = one internode of one axon; produce MBP, PMP22, P0; target in GBS, CMT (Charcot-Marie-Tooth hereditary neuropathy). Satellite cells: surround neuronal soma in ganglia; similar function to astrocytes in CNS; NOT involved in myelination. In GBS, nerve conduction studies show markedly slowed conduction velocity + prolonged distal latencies = demyelination pattern.
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A patient suffers a penetrating knife injury to the arm, completely severing the ulnar nerve at the medial epicondyle. One week later, the axon and myelin sheath of the ulnar nerve distal to the injury site have degenerated (Wallerian degeneration). Which cells proliferate after Wallerian degeneration to fill the endoneurial tube, forming "Bands of Büngner" that guide axonal regeneration?
Correct. After Wallerian degeneration (axon + myelin degenerate distal to injury): Schwann cells dedifferentiate, proliferate, and phagocytose myelin debris (with macrophage help). They fill the endoneurial tube → form longitudinal columns = Bands of Büngner. These Schwann cell columns express surface molecules (N-CAM, L1/NgCAM, GDNF, BDNF) that guide the regenerating axon from the proximal stump.
Peripheral nerve injury classification (Seddon): Neurapraxia (Grade I) = focal demyelination, no axon loss → full recovery, no Wallerian degeneration. Axonotmesis (Grade II) = axon disrupted, endoneurium intact → Wallerian degeneration + full recovery guided by intact endoneurial tube; rate 1–4 mm/day + 1 month delay. Neurotmesis (Grade III) = entire nerve severed → Wallerian degeneration + incomplete recovery (needs surgical repair); Schwann cells form disorganised mass without guiding tube. Sunderland classification (5 grades) adds detail. Tinel's sign = tingling when tapping over regenerating nerve tip = tracks recovery.
Schwann cells form Bands of Büngner. Wallerian degeneration sequence: (1) Axon distal to cut → fragmentation (12–24h); (2) Myelin breaks down → myelin "ovoids" → lipid debris; (3) Schwann cells dedifferentiate + proliferate (repair Schwann cells); (4) Macrophages recruited → phagocytose myelin lipid debris; (5) Schwann cells form Bands of Büngner (longitudinal columns in empty endoneurial tubes); (6) Regenerating axon grows at 1–4 mm/day guided by Büngner bands. CNS regeneration fails because: no Büngner bands, oligodendrocytes inhibitory (Nogo, MAG, OMgp), dense glial scar (CSPG = chondroitin sulphate proteoglycans block axon growth).
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A histology section of the cerebral white matter is immunostained with an antibody against GFAP (glial fibrillary acidic protein). The cells that stain positively (GFAP-positive) with star-like processes are:
Correct. Astrocytes are the GFAP-positive cells of the CNS. GFAP (glial fibrillary acidic protein) is an intermediate filament protein specific to astrocytes → used as a marker for astrocytes and astrocytic tumours (astrocytoma, glioblastoma multiforme — the most common primary brain tumour). Astrocytes have star-shaped processes with end-feet that contact blood vessels (blood-brain barrier) and synapses.
Glial cell markers: GFAP → astrocytes (also used to diagnose astrocytoma/GBM on biopsy). MBP, PLP → oligodendrocytes (demyelination → MBP in CSF, spinal fluid). Iba-1, CD68, CD163 → microglia/macrophages. Synaptophysin → neurons (used in neuroendocrine tumours). NeuN → neuronal nuclei. S100 → Schwann cells + astrocytes + melanocytes (used in peripheral nerve sheath tumours, melanoma). Vimentin → intermediate filaments of mesenchymal cells (also immature glia). In GBM biopsy: GFAP+ + EGFR amplification + PTEN loss + IDH wildtype = GBM (most malignant, grade 4).
Astrocytes (GFAP+) is the answer. GFAP = key astrocyte marker. Oligodendrocytes (CNS myelin): MBP, PLP, CNPase positive; small round nuclei; GFAP negative. Microglia (CNS macrophages): Iba-1, CD68 positive; ramified processes (resting); activated → ameboid; GFAP negative. Ependymal cells: ciliated columnar cells lining ventricles; GFAP negative. Astrocyte functions: (1) BBB (via end-feet); (2) K⁺ spatial buffering; (3) Glutamate uptake (astrocytic GLT1/GLAST); (4) Glycogen storage; (5) Structural support. Reactive gliosis: astrocytes hypertrophy after injury → glial scar (GFAP++); neuroprotective but inhibits axon regeneration.
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A patient from rural Tamil Nadu presents with a hypopigmented anaesthetic patch on the forearm and a palpable thickened cord in the ulnar nerve groove behind the medial epicondyle. Slit-skin smear is positive for acid-fast bacilli. This is leprosy. Mycobacterium leprae causes peripheral neuropathy in this disease because it specifically infects which cell in the peripheral nervous system?
Correct. M. leprae is unique in specifically targeting Schwann cells (the glial cells of the peripheral nervous system). M. leprae binds to the G domain of laminin-α2 on the Schwann cell surface via its shed PGL-1 antigen, enters Schwann cells, and replicates within them → demyelination + axonal injury → sensory loss, motor weakness, and autonomic dysfunction in the distribution of the affected nerve.
Leprosy neuropathy: anaesthesia + motor weakness + autonomic loss = classic triad. Pure neural leprosy (no skin lesions) is common in India → diagnosis by nerve biopsy. Most commonly affected nerves: Ulnar (claw hand, loss of sensation medial 1.5 fingers), Radial (wrist drop), Common peroneal (foot drop), Posterior tibial (plantar sensation loss → trophic ulcer), Great auricular (neck), Facial (lagophthalmos → corneal exposure). Disability prevention: early MDT (multi-drug therapy), physiotherapy, protective footwear. India is endemic (33% of global leprosy cases); WHO 2030 target = zero grade 2 disability in new cases.
Schwann cells are the specific target of M. leprae in leprosy. M. leprae is the ONLY bacterium known to invade peripheral nerves via Schwann cell infection. Mechanism: PGL-1 (phenolic glycolipid-1) binds laminin-2 receptor on Schwann cells → entry → replication → demyelination. Peripheral nerve changes: (1) Tuberculoid (paucibacillary): granulomas WITHIN nerve → fibrosis → severe nerve thickening (palpable); (2) Lepromatous (multibacillary): Schwann cells packed with bacilli (Virchow cells/foam cells) → diffuse nerve enlargement. Palpable nerves: great auricular (most easily palpated), ulnar, common peroneal, radial cutaneous, posterior tibial.
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Multiple sclerosis (MS) is an autoimmune disease of the CNS where myelin is destroyed but the peripheral nervous system is spared. This specificity is because the autoimmune attack targets a protein specific to CNS myelin. A major reason CNS myelin is NOT regenerated effectively after MS plaques form is that:
Correct. Oligodendrocytes have limited regenerative capacity compared to Schwann cells. In the early/acute MS phase, oligodendrocyte precursor cells (OPCs) can remyelinate (shadow plaques). However, chronic MS lesions develop a chronic inactive plaque with oligodendrocyte loss and no remyelination. Additionally, CNS inhibitory factors (Nogo-A, MAG, OMgp on oligodendrocytes and myelin) and CSPG in the glial scar prevent axon and oligodendrocyte process extension.
CNS vs PNS regeneration after demyelination: PNS (Schwann cells): dedifferentiate, proliferate, phagocytose debris, form Büngner bands → efficient remyelination; PNS axons can regenerate at 1–4 mm/day. CNS (oligodendrocytes): OPCs exist in white matter; can partially remyelinate in early MS → "shadow plaques" (thin remyelinated axons); chronic lesions: astrogliosis + inhibitory environment → incomplete remyelination → permanent axon loss → disability. MS demographics: young adults (20–40 years), female:male 3:1, predominantly Caucasian; Indian MS = less common but increasing; optic neuritis and transverse myelitis common presentations. MRI: periventricular white matter lesions (Dawson's fingers), McDonald criteria for diagnosis.
Limited oligodendrocyte regenerative capacity + CNS inhibitory environment is the answer. Compare PNS vs CNS regeneration: PNS = Schwann cells dedifferentiate and proliferate → Bands of Büngner → guide axon regeneration efficiently. CNS = oligodendrocytes have less regenerative capacity; OPCs can remyelinate partially in early lesions; chronic lesions = astrogliosis (GFAP+ glial scar) + Nogo/MAG/OMgp (inhibitory myelin-associated inhibitors) = blocks axon and OPC process extension. MS treatment targets inflammation (disease-modifying therapies — interferon-β, glatiramer, natalizumab) but none effectively promote remyelination (active research area).
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