Muscle and nerve histology
Muscle and nerve tissue: histology of muscle types, neurones and glia
Skeletal, cardiac and smooth muscle compared, the sarcomere and neuromuscular junction, neurones, glia, myelin and nerve injury for FCPS Part 1. Explains why gap junctions coordinate labour, why axonotmesis recovers and why the CNS does not regenerate.
Three muscle types
| Feature | Skeletal | Cardiac | Smooth |
|---|---|---|---|
| Striations | Yes | Yes | No |
| Nuclei | Many, peripheral (fused myoblasts) | One or two, central; branched cells | One, central; spindle cells |
| Junctions between cells | None; each fibre needs its own nerve ending | Intercalated discs (desmosomes, fascia adherens, gap junctions) | Gap junctions in single-unit (visceral) muscle |
| T tubules | At the A–I junction, forming triads | At the Z line, forming dyads | None (caveolae) |
| Calcium source | Sarcoplasmic reticulum | Extracellular calcium triggers SR release | Extracellular plus SR |
| Calcium binds | Troponin C | Troponin C | Calmodulin, activating myosin light chain kinase |
| Repair | Limited, from satellite cells | Almost none; scar after MI | Good; cells divide |
- Gap junctions (connexin channels) let ions pass cell to cell, so cardiac muscle and single-unit smooth muscle contract as a functional syncytium. Near term, oestrogen raises the number of connexin-43 gap junctions in the myometrium (and oxytocin receptors), so contractions spread over the whole uterus.
- The upper third of the oesophagus is skeletal muscle, the middle third mixed, the lower third smooth.
The sarcomere
- Runs from Z line to Z line. The A band is the length of the thick myosin filaments; the I band has thin actin filaments only; the H zone is the central part of the A band with myosin only; the M line is its centre.
- Filaments slide, they do not shorten. During contraction the I band and H zone shorten (the H zone may disappear) and the sarcomere shortens, but the A band stays constant. In relaxation the I band and H zone widen again.
- Titin provides elasticity; dystrophin links actin to the membrane complex. Absent dystrophin causes Duchenne muscular dystrophy (X-linked); reduced or abnormal dystrophin causes Becker.
| Fibre type | Type I (slow, red) | Type II (fast, white) |
|---|---|---|
| Metabolism | Oxidative, many mitochondria, myoglobin | Glycolytic |
| Fatigue | Resistant | Rapid |
| Example | Soleus, postural muscles | Sprinting muscles |
- Mitochondrial myopathies (MELAS: myopathy, encephalopathy, lactic acidosis, stroke-like episodes; deafness, diabetes, short stature) show ragged red fibres on modified Gomori trichrome: subsarcolemmal clumps of abnormal mitochondria. Inheritance is maternal; severity varies with heteroplasmy.
The neuromuscular junction
Motor nerve terminals release acetylcholine onto nicotinic receptors concentrated on the crests of junctional folds; acetylcholinesterase in the basal lamina ends the signal. In myasthenia gravis, antibodies to the acetylcholine receptor cause complement-mediated damage: fewer receptors on flattened, simplified postsynaptic folds, so endplate potentials fail with repeated use (fatigable ptosis, diplopia, chewing weakness late in meals). Aminoglycosides and magnesium can worsen it.
Neurones
- Multipolar: motor neurones and most CNS neurones. Bipolar: retina, olfactory epithelium, cochlear and vestibular ganglia. Pseudounipolar: dorsal root and cranial sensory ganglia.
- Nissl bodies (rough ER) fill the cell body and dendrites but not the axon hillock or axon; after axonal injury they disperse (chromatolysis) as the cell makes repair proteins.
- Axonal transport: anterograde by kinesin, retrograde by dynein (route for rabies, tetanus toxin, herpes viruses).
Glial cells
| Cell | Origin | Function |
|---|---|---|
| Astrocytes | Neuroectoderm | Buffer K⁺ and take up glutamate; end-feet support the blood–brain barrier (the barrier itself is endothelial tight junctions); form the gliotic scar; marker GFAP. They do not fire action potentials |
| Oligodendrocytes | Neuroectoderm | CNS myelin; one cell myelinates segments of many axons; target in multiple sclerosis |
| Microglia | Mesoderm (monocyte lineage) | CNS macrophages; foamy cleaners in infarcts; HIV reservoir |
| Ependymal cells | Neuroectoderm | Ciliated lining of ventricles and central canal; choroid plexus epithelium |
| Schwann cells | Neural crest | PNS myelin; one cell per internode of one axon; guide regeneration; target in Guillain–Barré |
- Alzheimer type II astrocytes: enlarged astrocytes with large, pale, vesicular nuclei in the cortex and basal ganglia in hepatic encephalopathy (they detoxify ammonia into glutamine and swell). Nothing to do with Alzheimer dementia.
Myelin and conduction
- Myelin insulates internodes so the impulse jumps between nodes of Ranvier (saltatory conduction), which is faster and uses less energy. The node is the gap without myelin, packed with voltage-gated Na⁺ channels; fast K⁺ channels sit mainly under the myelin next to the node.
| Fibre | Myelin | Carries |
|---|---|---|
| Aα | Thick | Motor to extrafusal muscle, proprioception (fastest) |
| Aβ | Thick | Touch, pressure |
| Aγ | Medium | Motor to muscle spindles |
| Aδ | Thin | Fast sharp pain, cold |
| B | Thin | Preganglionic autonomic |
| C | None | Slow burning pain, warmth, postganglionic autonomic |
- Large myelinated fibres (motor, proprioception) are most vulnerable to compression; small C fibres are most sensitive to local anaesthetics.
Peripheral nerve layers and injury
- Endoneurium around each axon, perineurium around each fascicle (blood–nerve barrier), epineurium around the nerve.
| Seddon grade | What is damaged | Recovery |
|---|---|---|
| Neurapraxia | Focal demyelination, axon intact; conduction block at the lesion, normal conduction below | Full, in days to weeks (tourniquet palsy, Saturday night palsy) |
| Axonotmesis | Axon divided, endoneurial tubes and sheaths intact; Wallerian degeneration distally; denervation potentials on EMG after 2–3 weeks | Good, by regrowth at about 1 mm/day; advancing Tinel sign; proximal muscles recover first |
| Neurotmesis | Whole nerve divided | Poor without surgical repair |
- After division, the proximal axon sprouts. If sprouts cannot find the distal tubes they form a traumatic (amputation) neuroma: a tender lump of disorganised small fascicles, Schwann cells and fibrous tissue that gives shooting pain on pressure (different from phantom limb pain).
- Misdirected regrowth: after Bell palsy, parasympathetic fibres meant for the submandibular and sublingual glands can grow into the greater petrosal route to the lacrimal gland, so the eye waters when eating (crocodile tears). Frey syndrome is the same idea after parotid surgery (salivary fibres to sweat glands).
- CNS axons do not regenerate well because oligodendrocyte myelin inhibitors and the astrocytic scar block them, and oligodendrocytes do not form guiding tubes.
Remember Oligodendrocytes wrap many CNS axons; Schwann cells wrap one PNS internode and help it regrow.
Exam trap During contraction the A band does not change; the I band and H zone shorten.
Exam trap Skeletal muscle fibres are not joined by gap junctions; cardiac and smooth muscle are.
How FCPS asks about this
- Change allowing coordinated labour contractions: more connexin gap junctions in the myometrium.
- True statement about astrocytes: buffer K⁺, support the blood–brain barrier, fire no action potentials.
- Myelin in the CNS: oligodendrocytes; demyelination in MS.
- Wrist drop recovering with advancing Tinel sign: axonotmesis; tourniquet palsy with conduction block is neurapraxia.
- Tender lump in an amputation stump: traumatic neuroma.
- Eye waters when eating after Bell palsy: misrouted salivary fibres reaching the lacrimal gland.
- Myasthenia gravis at the NMJ: fewer receptors on simplified postsynaptic folds; ragged red fibres in mitochondrial myopathy.
Test yourself on this topic
5 of the 20 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A year after a below-knee amputation, a man has a very tender lump in the stump that causes shooting pain when pressed. Excision shows a disorganised tangle of small nerve fascicles with Schwann cells and fibrous tissue. Which of the following is this lesion?
Answer: Traumatic neuroma
When a nerve is cut and the axon sprouts from the proximal stump cannot find a distal stump, they grow in a disorganised way into scar tissue. The result is a traumatic neuroma: a non-neoplastic tangle of axons, Schwann cells, perineurial cells and fibroblasts. It is often painful and tender to pressure. Surgeons reduce the risk by cutting nerves cleanly and allowing them to retract away from the scar.
Traumatic neuroma
- Axon sprouts with no distal stump
- Disorganised fascicles in scar
- Not a true tumour
- Painful, tender stump lump
Remember Lost axons tangle into a neuroma.
Exam trap Phantom limb pain is different: it is felt in the missing part, not at a tender point in the stump.
Why the other options are wrong
- Schwannoma A benign tumour of Schwann cells with Antoni A and B areas.
- Neurofibroma A tumour with mixed cells in a myxoid stroma, often in NF1.
- Morton neuroma Perineural fibrosis of a plantar digital nerve, not an amputation stump.
- Ganglion cyst A mucin-filled cyst near joints or tendon sheaths.
A 55-year-old man with cirrhosis dies after repeated episodes of hepatic encephalopathy. Brain histology shows enlarged glial cells with large, pale, vesicular nuclei in the cortex and basal ganglia, with few neuronal changes. Which cells are these?
Answer: Alzheimer type II astrocytes
Astrocytes are the only brain cells with glutamine synthetase, so they detoxify ammonia by combining it with glutamate to make glutamine. In liver failure, ammonia reaching the brain is converted to glutamine inside astrocytes, which draws in water and swells them. Long-standing exposure produces Alzheimer type II astrocytes, with large pale nuclei, the typical histological change of hepatic encephalopathy. They are unrelated to Alzheimer disease.
Ammonia and astrocytes
- Only astrocytes have glutamine synthetase
- Ammonia + glutamate glutamine
- Glutamine draws water: swelling
- Alzheimer type II astrocytes
Remember Liver failure brain: look at the astrocytes.
Exam trap The name is misleading: Alzheimer type II astrocytes have nothing to do with Alzheimer dementia.
Why the other options are wrong
- Activated microglia Microglia form nodules in infection; they do not detoxify ammonia.
- Swollen oligodendrocytes Oligodendrocytes form myelin and are not the cells affected.
- Ependymal cells Ependymal cells line the ventricles.
- Reactive Schwann cells Schwann cells are in peripheral nerves, not the brain.
In group fascicular repair of a divided median nerve, which sheath does the surgeon suture?
Answer: Perineurium
A peripheral nerve has three connective tissue layers. Endoneurium surrounds each axon with its Schwann cell, perineurium encloses each fascicle and forms the blood–nerve barrier, and epineurium surrounds the whole nerve and groups of fascicles. Standard repair sutures the epineurium, while group fascicular repair places fine sutures in the perineurium to align fascicles more precisely. The endoneurium is too delicate to suture.
Nerve sheaths
- Endoneurium: each axon
- Perineurium: each fascicle, barrier
- Epineurium: whole nerve
- Fascicular repair: perineurium
Remember Endo, peri, epi: inside out.
Exam trap Repair must be tension-free; a gap is better bridged with a nerve graft than closed under tension.
Why the other options are wrong
- Epineurium Sutured in standard epineurial repair, not fascicular repair.
- Endoneurium Surrounds single axons; too fine to suture.
- Myelin sheath Not a connective tissue sheath.
- Neurilemma The Schwann cell outer layer; not sutured.
Which glial cell is NOT a type of macroglia?
Answer: Microglia
Macroglia arise from neuroectoderm: astrocytes, oligodendrocytes and ependymal cells in the CNS, and Schwann cells and satellite cells in the PNS. Microglia are different: they come from mesoderm (bone marrow monocyte lineage) and act as the resident macrophages of the brain, becoming multinucleated giant cells in HIV encephalitis.
Glial cells
- Macroglia: neuroectoderm
- Astrocyte, oligodendrocyte, ependymal
- PNS: Schwann, satellite
- Microglia: mesoderm, brain macrophage
Remember Micro is the odd one out: it is a macrophage.
Exam trap Gliosis (brain scarring) is done by astrocytes, not fibroblasts.
Why the other options are wrong
- Astrocyte Macroglia: blood–brain barrier support, scar (gliosis).
- Oligodendrocyte Macroglia: CNS myelin.
- Ependymal cell Macroglia: lines ventricles.
- Schwann cell Peripheral macroglia: PNS myelin.
After a 2-hour knee operation under an upper-thigh tourniquet, a man cannot dorsiflex his foot. Sensation is mildly reduced, and he recovers completely within 4 weeks. Nerve studies showed a conduction block at the tourniquet level with normal conduction below it. What was the pathology?
Answer: Focal demyelination, axon intact
This is neurapraxia, the mildest injury. Pressure and ischaemia cause focal damage to the myelin sheath, blocking conduction at that point, while the axon remains in continuity. Because there is no Wallerian degeneration, the nerve conducts normally below the lesion and no regrowth is needed; recovery occurs in days to weeks as myelin is repaired. Motor fibres are usually more affected than sensory fibres.
Neurapraxia
- Focal demyelination
- Axon intact
- No Wallerian degeneration
- Recovers in days to weeks
Remember Block, not break.
Exam trap Large fibres conveying motor power and proprioception are more vulnerable to compression than pain fibres.
Why the other options are wrong
- Wallerian degeneration of axons Would cause denervation and slow recovery over months.
- Complete division of the nerve Would not recover spontaneously.
- Neuroma formation at the cuff Forms after axon division, not compression.
- Death of anterior horn cells Tourniquets injure the nerve locally, not cell bodies in the cord.
Where this sits in the CPSP syllabus
- Paper 1: General and special histology, Muscle and nerve tissue
- Surgery & Allied, Paper 2: Histology for surgery, Muscle and nerve tissue
- Medicine & Allied, Paper 2: Histology: liver, pancreas, spleen, kidney, brain, gut, Muscle and nerve tissue
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