Muscle — MRCS Part B Applied surgical science and critical care

An applied sciences station that starts with tetanus and moves through the structure and physiology of muscle to the cardiac action potential and the drugs that act on it.

Tetanus

Clostridium tetani in a dirty wound produces tetanospasmin, which travels up the motor axons to the spinal cord and blocks the release of glycine and GABA from the inhibitory interneurones, so the motor neurones fire unopposed: trismus, risus sardonicus, opisthotonus, painful spasms set off by any stimulus, and autonomic instability. Management is airway protection and sedation in intensive care, with paralysis and ventilation if the spasms threaten breathing, human tetanus immunoglobulin to neutralise unbound toxin, metronidazole, debridement of the wound, and a full course of vaccine, since the disease does not confer immunity. Magnesium helps the spasms and the autonomic storms.

Types of muscle

Skeletal, striated and voluntary, made of long multinucleate fibres; cardiac, striated, involuntary, with branching cells joined by intercalated discs; and smooth, unstriated and involuntary, in vessels, gut, airways, bladder and uterus. Skeletal fibres are classed by their myosin and metabolism: type I slow, red, oxidative and fatigue-resistant, for posture; type IIa fast and oxidative; type IIb fast, white, glycolytic and quick to fatigue, for sprinting. The proportion is fixed by the motor neurone that supplies the fibre.

The sarcomere

The contractile unit, from one Z line to the next, about 2.5 micrometres long. Thick filaments of myosin make the A band; thin filaments of actin, with tropomyosin lying in the groove and troponin at intervals, run in from the Z lines to make the I band and overlap the thick filaments; the H zone in the middle of the A band is thick filament alone, with the M line in its centre and titin holding the thick filaments in place. Myosin is the motor: its heads bind actin, hydrolyse ATP and bend, pulling the thin filaments towards the middle. Actin is the track: it does nothing but be pulled, once calcium has moved tropomyosin off its binding sites.

Sliding filaments and calcium

Contraction is the thin filaments sliding over the thick ones: the sarcomere shortens, the I band and H zone narrow, the A band stays the same length. Calcium is the switch. It is stored in the sarcoplasmic reticulum, the terminal cisternae lying against the T-tubules, which are inward folds of the membrane that carry the action potential to the middle of the fibre. The voltage change in the T-tubule opens the ryanodine receptor of the reticulum, calcium floods out and binds troponin C, tropomyosin moves, the myosin heads engage, and the cycle of binding, power stroke, ATP-driven release and re-cocking repeats until the calcium is pumped back. That is excitation-contraction coupling. Rigor mortis is the cycle stopping for want of ATP with the heads still bound.

Smooth and cardiac muscle

Smooth muscle has no sarcomeres or troponin: calcium enters mainly from outside, binds calmodulin, and activates myosin light-chain kinase; it contracts slowly, holds tone for hours at little cost, and is controlled by autonomic nerves, hormones and stretch, with gap junctions spreading the contraction through the sheet. Cardiac muscle is striated like skeletal muscle but its cells branch and are electrically coupled through intercalated discs, so the whole ventricle contracts as one; it cannot be tetanised, it depends on extracellular calcium entering through L-type channels to trigger release from the reticulum, it has an intrinsic rhythm, and it cannot incur an oxygen debt.

The cardiac action potential

Phase 0, a fast upstroke from sodium entry; phase 1, a brief early repolarisation; phase 2, the plateau, held at about zero for 200 milliseconds as calcium entering through L-type channels balances potassium leaving; phase 3, repolarisation by potassium efflux; phase 4, the resting potential of about −90 mV. The plateau is what makes cardiac muscle different: the long absolute refractory period means the ventricle has relaxed before it can be excited again, so it cannot go into tetany, and the calcium that enters during the plateau is what triggers contraction and sets its strength.

Pacemaking

The sinoatrial node has no stable resting potential: a slow inward "funny" sodium current drifts it up to threshold, a calcium spike fires, and the cycle repeats about 70 times a minute, fastest of all the cardiac tissue, so it sets the rate. The atrioventricular node conducts slowly, delaying the impulse so the atria empty first, and has its own rhythm of about 40 to 60 that takes over if the sinus node fails. Sympathetic stimulation steepens the drift and speeds the heart; the vagus flattens it and slows it.

Digoxin

It blocks the sodium-potassium pump of the myocyte, so intracellular sodium rises, the sodium-calcium exchanger slows, and calcium accumulates in the cell: contraction is stronger. It also increases vagal tone at the atrioventricular node, slowing conduction, which is why it controls the ventricular rate in atrial fibrillation. Its therapeutic window is narrow; toxicity, worse in hypokalaemia and renal failure, gives nausea, yellow vision, bradycardia and any arrhythmia.