Physiology: Nerve, muscle and autonomic systems, exercise, pregnancy and ageing

Neural, muscular and autonomic physiology

• Nerve: The Neuron and Nerve Fibres | The Action Potential | Conduction and Myelination | Synapses and Neurotransmitters | Sensory Receptors and Pathways | Motor Pathways and Reflexes
• Muscle: The Neuromuscular Junction | Skeletal Muscle Contraction | Muscle Fibre Types, Exercise and Fatigue | Smooth and Cardiac Muscle
• Autonomic nervous system: Organisation of the Autonomic Nervous System | Autonomic Receptors and Drugs | Autonomic Effects on Organs | Autonomic Disorders and Toxidromes
• Revision: Nerve, Muscle and Autonomic at a Glance | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

⚡ Nerve, muscle and autonomic physiology — page 2 of the Anatomy and Physiology chapter. Excitable tissues explain a huge range of clinical medicine: local anaesthetics, demyelination, myasthenia gravis, neuromuscular blockers, upper and lower motor neurone signs, and the many drugs that act on the autonomic nervous system. Learn the mechanisms here and the drugs and diseases make sense.
Your four questions for every nerve or muscle problem: Where is the lesion — neuron, axon, myelin, junction or muscle? Is it upper or lower motor neurone? Which receptor or channel is involved — and which drugs act there? Which autonomic effects explain the signs?

The Neuron and Nerve Fibres

• Structure — cell body (soma — nucleus, Nissl substance), dendrites (receive input), axon (conducts away — axon hillock is where action potentials start), axon terminals (release neurotransmitter).
• Axonal transport — anterograde (kinesin) and retrograde (dynein) along microtubules — route for tetanus toxin, rabies, herpes viruses and polio to reach the CNS; impaired by vincristine (neuropathy).
• Nerve fibre classification:

  Fibre	Myelin	Speed	Function
  Aα	Heavy	Fastest (70–120 m/s)	Motor to skeletal muscle; muscle spindle (Ia) and Golgi tendon organ (Ib) afferents
  Aβ	Myelinated	Fast	Touch, vibration, proprioception
  Aγ	Myelinated	Medium	Motor to muscle spindles
  Aδ	Thin myelin	5–30 m/s	Fast, sharp pain, cold
  B	Thin myelin	Medium	Preganglionic autonomic
  C	Unmyelinated	Slowest (0.5–2 m/s)	Slow, burning pain, warmth, itch; postganglionic autonomic

• Local anaesthetics block small fibres first — pain and temperature go before touch and motor function; autonomic B fibres are also sensitive (hypotension with spinals).
• Peripheral nerve structure — axons wrapped in endoneurium, grouped in fascicles (perineurium), the whole nerve covered by epineurium.
• Nerve injury (Seddon):
  • Neurapraxia — conduction block, axon intact (compression — "Saturday night palsy") — full recovery in weeks.
  • Axonotmesis — axon divided, sheath intact — Wallerian degeneration distally, regrowth about 1 mm a day (1 inch a month) — good recovery.
  • Neurotmesis — whole nerve divided — needs surgical repair; incomplete recovery.
• Tinel's sign — tingling on tapping over a regenerating or compressed nerve (tracks regrowth).

The Action Potential

• Action potential — a rapid, all-or-none reversal of membrane potential that travels along excitable membranes.
• Phases (neuron):
  • Threshold — a stimulus depolarises the membrane to about –55 mV.
  • Depolarisation — voltage-gated Na⁺ channels open → Na⁺ rushes in → potential rises to about +30 mV (positive feedback).
  • Repolarisation — Na⁺ channels inactivate; voltage-gated K⁺ channels open → K⁺ leaves.
  • Hyperpolarisation (undershoot) — K⁺ channels close slowly.
  • Na⁺/K⁺-ATPase restores gradients (only a tiny number of ions move each time).
• Refractory periods:
  • Absolute — no stimulus can trigger another action potential (Na⁺ channels inactivated) — limits firing rate and makes conduction one-way.
  • Relative — a stronger stimulus is needed (during hyperpolarisation).
• Drugs and toxins acting on sodium channels:
  • Local anaesthetics (lidocaine), class I antiarrhythmics (flecainide), anticonvulsants (carbamazepine, phenytoin, lamotrigine) — block Na⁺ channels.
  • Tetrodotoxin (pufferfish) and saxitoxin (shellfish) — block Na⁺ channels — paralysis.
  • Tricyclic antidepressant overdose — Na⁺ channel block → broad QRS — treated with sodium bicarbonate.
• Drugs acting on potassium channels — amiodarone and sotalol (class III — prolong repolarisation and QT), sulfonylureas (close K_ATP channels in beta cells → insulin release), nicorandil and minoxidil (open K⁺ channels — vasodilate).
• Cardiac action potentials — longer (plateau from L-type Ca²⁺ channels — phase 2); pacemaker cells (SA node) depolarise spontaneously via the "funny" current (I_f — ivabradine blocks it) — see the Cardiology chapter.

Conduction and Myelination

• Unmyelinated fibres — continuous conduction along the whole membrane — slow.
• Myelinated fibres — saltatory conduction — the action potential "jumps" between nodes of Ranvier (where Na⁺ channels cluster) — fast and energy-efficient.
• Conduction velocity increases with axon diameter and myelination; falls with cold.
• Myelin — made by oligodendrocytes in the CNS (one cell myelinates many axons) and Schwann cells in the PNS (one cell per segment of one axon — supports regeneration).
• Demyelination — slowed conduction, conduction block, ephaptic transmission (cross-talk) — symptoms worse with heat (Uhthoff's phenomenon in MS):
  • CNS — multiple sclerosis, neuromyelitis optica, ADEM, central pontine myelinolysis (rapid sodium correction), B12 deficiency (subacute combined degeneration), leukodystrophies.
  • PNS — Guillain–Barré syndrome, CIDP, Charcot–Marie–Tooth type 1, diphtheria.
• Nerve conduction studies:
  • Demyelinating neuropathy — slowed conduction velocity, prolonged latencies, conduction block; amplitudes relatively preserved.
  • Axonal neuropathy — reduced amplitude, near-normal velocity (diabetes, alcohol, drugs, vasculitis).
• EMG — muscle electrical activity — denervation (fibrillations — neuropathy, MND) vs myopathy (small, short, polyphasic units).

Synapses and Neurotransmitters

• Chemical synapse — action potential reaches the terminal → voltage-gated Ca²⁺ channels open → Ca²⁺ triggers vesicle fusion (SNARE proteins — cleaved by botulinum toxin) → neurotransmitter crosses the cleft → binds receptors → signal ends by enzyme breakdown, reuptake or diffusion.
• Postsynaptic potentials — excitatory (EPSP — depolarising — glutamate) and inhibitory (IPSP — hyperpolarising — GABA, glycine); summate (temporal and spatial) at the axon hillock.
• Electrical synapses — gap junctions (heart, some CNS) — fast, two-way.
• Main neurotransmitters:

  Transmitter	Role	Clinical links
  Glutamate	Main excitatory CNS transmitter (NMDA, AMPA receptors)	Excitotoxicity in stroke; ketamine and memantine block NMDA
  GABA	Main inhibitory CNS transmitter (GABA-A — Cl– channel)	Benzodiazepines, barbiturates, propofol, alcohol enhance it; withdrawal → seizures
  Glycine	Inhibitory in the spinal cord	Blocked by strychnine and tetanus toxin (spasms)
  Acetylcholine	Neuromuscular junction, autonomic ganglia, parasympathetic, CNS (memory)	Myasthenia, Alzheimer's (cholinesterase inhibitors), organophosphates
  Dopamine	Movement (nigrostriatal), reward (mesolimbic), prolactin inhibition (tuberoinfundibular)	Parkinson's (loss); schizophrenia (antipsychotics block D2 — EPSEs, high prolactin)
  Noradrenaline	Sympathetic postganglionic; arousal (locus coeruleus)	Antidepressants (SNRIs), vasopressors
  Serotonin (5-HT)	Mood, sleep, gut motility, vomiting (raphe nuclei)	SSRIs, triptans (5-HT1), ondansetron (5-HT3), serotonin syndrome
  Histamine	Wakefulness, gastric acid, allergy	Sedating antihistamines; H2 blockers
  Endorphins, substance P	Pain modulation	Opioids act at opioid receptors

Sensory Receptors and Pathways

• Receptor types — mechanoreceptors (Meissner — light touch; Pacinian — vibration; Merkel — pressure; Ruffini — stretch), thermoreceptors, nociceptors (free nerve endings), proprioceptors (muscle spindles — length; Golgi tendon organs — tension; joint receptors), chemoreceptors, photoreceptors.
• Adaptation — rapidly adapting (Pacinian — vibration) vs slowly adapting (Merkel, nociceptors — pain persists).
• Ascending pathways:

  Pathway	Modalities	Course and crossing
  Dorsal columns (medial lemniscus)	Fine touch, vibration, proprioception	Ascend ipsilaterally in the dorsal columns (gracile — legs; cuneate — arms) → cross in the medulla → thalamus → cortex
  Spinothalamic tract	Pain, temperature, crude touch	Synapse in the dorsal horn → cross within 1–2 segments (anterior white commissure) → ascend contralaterally → thalamus
  Spinocerebellar tracts	Unconscious proprioception	To the cerebellum (ipsilateral)

• Clinical patterns:
  • Brown-Séquard (hemisection) — ipsilateral weakness and loss of vibration and proprioception; contralateral loss of pain and temperature.
  • Central cord (syringomyelia) — "cape-like" loss of pain and temperature (crossing fibres damaged) with preserved touch and vibration.
  • Anterior cord syndrome (anterior spinal artery) — weakness and loss of pain and temperature; dorsal columns spared.
  • Dorsal column loss — B12 deficiency, tabes dorsalis — sensory ataxia, positive Romberg's test.
• Dermatomes — the skin area supplied by one spinal nerve — key ones: C6 thumb, C7 middle finger, C8 little finger, T4 nipple, T10 umbilicus, L1 inguinal ligament, L4 medial shin, L5 dorsum of foot and big toe, S1 lateral foot and sole, S2–4 perianal (saddle).
• Referred pain — visceral and somatic afferents converge on the same spinal segment — heart (left arm, jaw — T1–4), diaphragm (shoulder tip — C3–5), appendix (umbilicus early — T10), gallbladder (right scapula), testis (umbilicus — T10).

Motor Pathways and Reflexes

• Upper motor neurone (UMN) — motor cortex → corticospinal tract → internal capsule → brainstem → crosses in the medullary pyramids (85% — lateral corticospinal tract) → synapses on the anterior horn cell.
• Lower motor neurone (LMN) — anterior horn cell → ventral root → peripheral nerve → muscle ("the final common pathway").
• UMN vs LMN signs:

  Sign	Upper motor neurone	Lower motor neurone
  Tone	Increased (spasticity — clasp-knife)	Reduced (flaccid)
  Weakness pattern	"Pyramidal" — extensors in arms, flexors in legs	In the distribution of the nerve or root
  Reflexes	Brisk; clonus	Reduced or absent
  Plantar	Extensor (Babinski)	Flexor or absent
  Wasting	Little (disuse only)	Marked
  Fasciculations	Absent	Present (anterior horn cell disease)
  Examples	Stroke, MS, cord compression	Peripheral neuropathy, radiculopathy, polio

• Mixed UMN and LMN signs — motor neurone disease (ALS), cervical myelopathy with radiculopathy, B12 deficiency (extensor plantars with absent ankle jerks), Friedreich's ataxia.
• Acute UMN lesions (spinal shock, early stroke) — initially flaccid with absent reflexes, becoming spastic over days to weeks.
• Stretch (myotatic) reflex — tap tendon → muscle spindle stretched → Ia afferent → monosynaptic synapse on the alpha motor neurone → contraction; also inhibits the antagonist (reciprocal inhibition).
• Reflex root values — ankle S1–2, knee L3–4, biceps C5–6, brachioradialis (supinator) C5–6, triceps C7–8 ("1-2 buckle my shoe, 3-4 kick the door, 5-6 pick up sticks, 7-8 lay them straight").
• Other motor systems — basal ganglia (initiation and smoothing of movement — Parkinson's, Huntington's) and cerebellum (coordination — ipsilateral signs — "DANISH": Dysdiadochokinesis, Ataxia, Nystagmus, Intention tremor, Slurred (scanning) speech, Hypotonia).

The Neuromuscular Junction

• Sequence:
  • Action potential reaches the motor nerve terminal.
  • Voltage-gated Ca²⁺ channels (P/Q type) open → Ca²⁺ enters.
  • Vesicles release acetylcholine (ACh) into the cleft.
  • ACh binds nicotinic receptors (ligand-gated cation channels) on the motor end plate → end-plate potential → muscle action potential.
  • Acetylcholinesterase rapidly breaks down ACh.
• Safety factor — far more ACh is released and more receptors exist than needed — so symptoms appear only when much of this reserve is lost.
• Disorders and drugs by site:

  Site	Disorder or toxin	Features
  Presynaptic Ca2+ channels	Lambert–Eaton myasthenic syndrome (antibodies — small cell lung cancer)	Proximal leg weakness, improves with repeated effort, reduced reflexes, autonomic symptoms (dry mouth)
  ACh release	Botulism (toxin cleaves SNARE proteins)	Descending flaccid paralysis, cranial nerve palsies, dilated pupils
  Postsynaptic nicotinic receptor	Myasthenia gravis (anti-AChR or anti-MuSK antibodies)	Fatigable weakness — ptosis, diplopia, bulbar, proximal; reflexes normal
  Postsynaptic receptor (drugs)	Neuromuscular blockers — suxamethonium (depolarising), rocuronium (competitive)	Paralysis for anaesthesia
  Acetylcholinesterase	Inhibitors — pyridostigmine (myasthenia treatment), neostigmine (reversal), donepezil (Alzheimer's); organophosphates (irreversible — poisoning, nerve agents)	Excess ACh — muscarinic and nicotinic effects

• Repetitive nerve stimulation — decrement in myasthenia gravis; increment (after exercise) in Lambert–Eaton.

Skeletal Muscle Contraction

• Structure — muscle → fascicles → muscle fibres (cells) → myofibrils → sarcomeres (the contractile unit, between Z lines).
• Sarcomere bands — A band (thick myosin filaments — length stays the same), I band (thin actin only — shortens), H zone (myosin only — shortens), Z line (anchors actin), M line (centre).
• Excitation–contraction coupling:
  • Muscle action potential spreads down T-tubules.
  • Dihydropyridine receptors (voltage sensors) mechanically open ryanodine receptors (RYR1) on the sarcoplasmic reticulum → Ca²⁺ release.
  • Ca²⁺ binds troponin C → tropomyosin moves → myosin-binding sites on actin exposed.
  • Cross-bridge cycling — myosin heads bind actin, pivot (power stroke), detach when ATP binds, re-cock as ATP is hydrolysed — the sliding filament mechanism.
  • Relaxation — Ca²⁺ pumped back into the SR (SERCA — needs ATP).
• Rigor mortis — no ATP after death → myosin can't detach from actin.
• Malignant hyperthermia — RYR1 mutation → uncontrolled Ca²⁺ release with volatile anaesthetics → rigidity, heat — dantrolene blocks RYR1.
• Grading force — recruiting more motor units (size principle — small units first) and increasing firing frequency (summation → tetanus).
• Length–tension relationship — maximum force at an optimal sarcomere length (overlap); the same principle underlies the Frank–Starling law in the heart.
• Motor unit — one motor neuron and the muscle fibres it supplies — small in eye and hand muscles (fine control), large in leg muscles.

Muscle Fibre Types, Exercise and Fatigue

• Fibre types:

  	Type I (slow oxidative — "red")	Type II (fast glycolytic — "white")
  Speed	Slow twitch	Fast twitch
  Metabolism	Aerobic — many mitochondria, myoglobin, capillaries	Anaerobic glycolysis (IIb/IIx); IIa intermediate
  Fatigue	Resistant	Fatigue quickly
  Examples	Postural muscles (soleus, back); endurance athletes	Eye muscles, gastrocnemius; sprinters
  Clinical	—	Type II atrophy with steroids and disuse

• Energy for exercise — stored ATP and creatine phosphate (first 10 seconds) → anaerobic glycolysis (to about 2 minutes — lactate) → aerobic metabolism of glucose and fat (prolonged exercise).
• Training effects — endurance training increases mitochondria, capillaries and VO₂ max; resistance training causes hypertrophy.
• Cardiovascular response to exercise — cardiac output rises up to 5-fold (heart rate and stroke volume), blood flow redistributed to muscle, BP rises (systolic), ventilation rises (anaerobic threshold — CPET).
• Sarcopenia — age-related loss of muscle mass and strength — key part of frailty; slowed by resistance exercise and protein.
• Creatine kinase (CK) — released from damaged muscle — raised after exercise, IM injections, falls, statins, myositis, rhabdomyolysis, hypothyroidism, muscular dystrophies; higher in people of Black African ancestry.
• Rhabdomyolysis — muscle breakdown → myoglobin (AKI), hyperkalaemia, hypocalcaemia, hyperphosphataemia — long lies, crush, exertion, drugs (statins), seizures.

Smooth and Cardiac Muscle

• Smooth muscle — in vessels, gut, airways, bladder, uterus, iris:
  • No troponin — Ca²⁺ binds calmodulin → activates myosin light-chain kinase → myosin phosphorylated → contraction.
  • Relaxation — myosin light-chain phosphatase (activated by cGMP — nitric oxide, nitrates, sildenafil prolongs cGMP).
  • Calcium sources — L-type channels (blocked by calcium channel blockers — amlodipine relaxes vascular smooth muscle) and the SR (IP₃-mediated — Gq receptors such as α1, angiotensin II, M3).
  • Single-unit (visceral — gut, uterus, bladder — connected by gap junctions, spontaneous activity) vs multi-unit (iris, large airways, vas deferens — individually innervated).
  • Can sustain tone with little energy ("latch state").
• Cardiac muscle:
  • Striated with intercalated discs (desmosomes and gap junctions) — functions as a syncytium.
  • Calcium-induced calcium release — L-type Ca²⁺ entry during the plateau triggers SR release (RYR2).
  • Long refractory period — prevents tetanus, allowing the heart to fill.
  • Contractility increased by sympathetic stimulation (β1 — cAMP), digoxin (raises intracellular Ca²⁺), and stretch (Frank–Starling).
• Drugs and smooth muscle — bronchodilators (β2 agonists ↑ cAMP; antimuscarinics block M3), nitrates (NO → cGMP), PDE5 inhibitors, oxytocin and ergometrine (uterine contraction), tocolytics (nifedipine, atosiban), antispasmodics (hyoscine butylbromide, mebeverine).

Organisation of the Autonomic Nervous System

• Autonomic nervous system (ANS) — involuntary control of the heart, smooth muscle and glands; two-neuron chain — preganglionic (CNS → ganglion) and postganglionic (ganglion → organ).
• Comparison:

  	Sympathetic	Parasympathetic
  Outflow	Thoracolumbar (T1–L2)	Craniosacral — cranial nerves III, VII, IX, X and S2–4
  Ganglia	Near the spinal cord (sympathetic chain, prevertebral — coeliac, mesenteric)	Near or in the target organ
  Fibres	Short preganglionic, long postganglionic	Long preganglionic, short postganglionic
  Ganglionic transmitter	ACh (nicotinic)	ACh (nicotinic)
  Organ transmitter	Noradrenaline (except sweat glands — ACh, muscarinic)	Acetylcholine (muscarinic)
  Overall role	"Fight or flight" — widespread	"Rest and digest" — localised

• Adrenal medulla — a modified sympathetic ganglion — preganglionic fibres stimulate chromaffin cells to release adrenaline (80%) and noradrenaline into blood (phaeochromocytoma).
• Vagus nerve (X) — about 75% of parasympathetic outflow — heart, lungs, gut to the splenic flexure; pelvic splanchnic nerves (S2–4) supply the distal colon, bladder and genitals.
• Control centres — hypothalamus, brainstem (vasomotor and cardiac centres in the medulla, nucleus tractus solitarius), limbic system.
• Enteric nervous system — the gut's own network (myenteric and submucosal plexuses) — modulated by the ANS; absent in Hirschsprung's disease; damaged in achalasia and Chagas disease.
• Horner's syndrome — interruption of the 3-neuron sympathetic pathway to the eye (hypothalamus → T1 cord → superior cervical ganglion → along the carotid) — ptosis, miosis, anhidrosis, enophthalmos — stroke (lateral medulla), Pancoast tumour, carotid dissection.

Autonomic Receptors and Drugs

• Adrenaline — α and β (β2 vasodilatation at low doses; α vasoconstriction at high doses); noradrenaline — mainly α1 and β1 (little β2).
• Indirect sympathomimetics — release or block reuptake of noradrenaline — amphetamines, cocaine, ephedrine, tyramine (cheese reaction with MAOIs).
• Anticholinergic burden — many drugs (tricyclics, oxybutynin, antihistamines, antipsychotics) add up to cause confusion, falls, constipation and retention in older people.

Autonomic Effects on Organs

• Baroreceptor reflex — fall in BP → reduced firing of carotid sinus (glossopharyngeal) and aortic arch (vagus) baroreceptors → ↑ sympathetic and ↓ vagal output → tachycardia and vasoconstriction (fails in autonomic failure — orthostatic hypotension).
• Vasovagal syncope — paradoxical vagal surge and sympathetic withdrawal → bradycardia and vasodilatation.
• Carotid sinus massage and the Valsalva manoeuvre increase vagal tone (terminate SVT).

Autonomic Disorders and Toxidromes

• Autonomic failure — orthostatic hypotension, fixed heart rate, constipation or diarrhoea, gastroparesis, urinary retention, erectile dysfunction, anhidrosis:
  • Causes — diabetes (commonest), Parkinson's disease, multiple system atrophy, pure autonomic failure, amyloidosis, Guillain–Barré (autonomic instability), spinal cord injury, ageing, drugs.
  • Tests — lying and standing BP (fall of 20 systolic or 10 diastolic within 3 minutes), heart rate variability with deep breathing, Valsalva, tilt-table testing.
  • Treatment — stop culprit drugs, fluids and salt, compression stockings, head-up tilt at night, fludrocortisone, midodrine (α1 agonist).
• Autonomic dysreflexia — spinal cord injury above T6 — a stimulus below the lesion (full bladder, constipation, pressure sore) causes massive sympathetic discharge → severe hypertension, headache, flushing and sweating above the lesion, bradycardia — sit up, remove the trigger (catheterise), nifedipine or GTN.
• Toxidromes:

  Toxidrome	Features	Causes
  Cholinergic (muscarinic and nicotinic)	DUMBELS — Diarrhoea, Urination, Miosis, Bradycardia/Bronchorrhoea/Bronchospasm, Emesis, Lacrimation, Salivation/Sweating; plus muscle fasciculations and weakness (nicotinic)	Organophosphates, nerve agents, carbamates — treat with atropine (large doses) and pralidoxime
  Anticholinergic	Hot, dry skin, flushed, dilated pupils, tachycardia, urinary retention, ileus, delirium	Tricyclics, antihistamines, atropine, hyoscine, datura
  Sympathomimetic	Hot, sweaty, dilated pupils, tachycardia, hypertension, agitation, seizures	Cocaine, amphetamines, MDMA
  Opioid	Pinpoint pupils, reduced consciousness, respiratory depression	Heroin, morphine, methadone — naloxone
  Sedative-hypnotic	Reduced consciousness, normal pupils, mild respiratory depression	Benzodiazepines, alcohol, Z-drugs

• Sweating distinguishes sympathomimetic (sweaty) from anticholinergic (dry) toxicity — both cause tachycardia and large pupils.

Nerve, Muscle and Autonomic at a Glance

Spot the Diagnosis

Exam-style Scenarios

1. A 65-year-old man has weakness of the right arm and leg. The right leg has increased tone, brisk reflexes and an upgoing plantar. There is no wasting.
Answer: Upper motor neurone lesion — left cerebral hemisphere (e.g. stroke) or above the decussation.

• UMN signs — spasticity, hyperreflexia, extensor plantar, pyramidal weakness, no wasting.
• Corticospinal fibres cross in the medulla — a left brain lesion causes right-sided weakness.
• Imaging (CT or MRI) to localise.

2. A 32-year-old woman has drooping eyelids and double vision that worsens through the day, and difficulty chewing. Reflexes and sensation are normal.
Answer: Myasthenia gravis.

• Antibodies against postsynaptic nicotinic ACh receptors (or MuSK) reduce the safety factor — fatigable weakness.
• Tests — AChR antibodies, repetitive nerve stimulation (decrement), single-fibre EMG, CT chest (thymoma).
• Treatment — pyridostigmine (acetylcholinesterase inhibitor), steroids and immunosuppression, thymectomy; avoid drugs that worsen it (aminoglycosides, magnesium).

3. A 40-year-old farmer collapses after spraying pesticide. He has pinpoint pupils, profuse sweating and salivation, wheeze, bradycardia and muscle twitching.
Answer: Organophosphate (cholinesterase inhibitor) poisoning — cholinergic toxidrome.

• Decontaminate (protect staff); airway, oxygen.
• Atropine in doubling doses until secretions dry and chest clear (blocks muscarinic effects).
• Pralidoxime (reactivates acetylcholinesterase — nicotinic effects); benzodiazepines for seizures; avoid suxamethonium.

4. A 75-year-old man with Parkinson's disease is dizzy when standing. Lying BP 145/80; standing 105/60 with no rise in heart rate.
Answer: Neurogenic orthostatic hypotension (autonomic failure).

• Failure of the baroreceptor reflex — no compensatory tachycardia or vasoconstriction.
• Review drugs (levodopa, alpha-blockers, antihypertensives, diuretics).
• Fluids, salt, compression, head-up bed tilt; midodrine or fludrocortisone; consider multiple system atrophy if severe.

5. A 28-year-old woman develops sudden left-sided weakness and loss of vibration sense in the left leg, and loss of pain and temperature in the right leg, after a stab wound to the back.
Answer: Left Brown-Séquard syndrome (hemisection of the left side of the cord).

• Ipsilateral UMN weakness (corticospinal — already crossed).
• Ipsilateral loss of vibration and proprioception (dorsal columns — cross in the medulla).
• Contralateral loss of pain and temperature (spinothalamic — crossed near entry).

Key Points

• Action potentials — Na⁺ influx depolarises, K⁺ efflux repolarises; Na⁺ channel blockers include local anaesthetics, class I antiarrhythmics and some anticonvulsants.
• Myelin speeds conduction — CNS demyelination (MS) vs PNS demyelination (GBS).
• Dorsal columns cross in the medulla; spinothalamic fibres cross at the segment — explains Brown-Séquard.
• Know UMN vs LMN signs and reflex root values.
• NMJ — LEMS (presynaptic), botulism (release), myasthenia (postsynaptic), organophosphates (cholinesterase).
• Skeletal muscle — Ca²⁺ from SR via RYR1 binds troponin; smooth muscle — Ca²⁺-calmodulin.
• Sympathetic — thoracolumbar, noradrenaline; parasympathetic — craniosacral, ACh.
• Learn receptor subtypes — they explain beta-blocker bronchospasm, tamsulosin hypotension and anticholinergic side effects.
• Sweating separates sympathomimetic from anticholinergic toxicity; DUMBELS = cholinergic.
• Autonomic dysreflexia above T6 — find and remove the trigger.

Guidelines and Further Reading

• Guyton and Hall: Textbook of Medical Physiology
• Crossman and Neary: Neuroanatomy — An Illustrated Colour Text
• Rang and Dale's Pharmacology (autonomic pharmacology)
• Association of British Neurologists: resources for medical students
• TOXBASE / National Poisons Information Service (toxidromes)
• Medical Schools Council: MLA content map — applied basic sciences
• BNF — for current doses