6.7 — When Muscle Goes Wrong

Muscle problems range from a cramp that wakes you at 3 a.m. to a condition that fills the bloodstream with muscle contents and shuts down the kidneys. This page covers both ends and everything useful in between, with the mechanism in each case, because the mechanisms explain the treatments.

Cramp

A sudden, painful, involuntary sustained contraction, usually in the calf, foot or thigh, lasting seconds to minutes and often leaving the muscle tender for hours.

The mechanism is not fully established, and the honest position is worth stating. The long-standing dehydration-and-electrolyte explanation is weaker than commonly assumed — studies comparing athletes who cramp with those who do not have generally found no consistent difference in hydration or electrolyte levels.

The better-supported explanation is altered neuromuscular control: muscle fatigue increases excitatory input from muscle spindles and reduces inhibitory input from the Golgi tendon organs, so the motor neuron pool becomes hyperexcitable and fires spontaneously. This explains why cramps happen in fatigued muscles, in shortened positions, and why stretching stops them.

Stretching works because it loads the Golgi tendon organ, which sits in the tendon and responds to tension by inhibiting the muscle. This is a direct, mechanical way to switch the muscle off, and it is why the treatment is immediate and effective: for a calf cramp, straighten the knee and pull the toes toward you.

Nocturnal leg cramps affect around a third of adults over 50 and their cause is usually unidentified. Quinine is effective and is no longer recommended, because of a real risk of severe blood disorders that outweighs the benefit for a benign condition. Stretching before bed, keeping bedclothes loose so the foot is not held pointed, and adequate hydration are what remains.

When a cramp is a warning sign: cramps with weakness, dark urine, or those that are new, severe and persistent may indicate an underlying muscle disease, thyroid disorder, or drug effect. And "cramp" in the calf that comes on reliably after a fixed walking distance and stops on resting is not cramp at all — it is intermittent claudication, from arterial narrowing, and it is a marker of widespread atherosclerosis (Chapter 18.1).

Strain and delayed soreness

A strain is a tear of muscle fibres, graded like a sprain (Chapter 5.8): grade 1 is a few fibres with minimal loss of strength, grade 2 is a partial tear with a palpable defect, grade 3 is a complete rupture.

Muscle heals partly by regeneration and partly by scar. Satellite cells — stem cells lying against the muscle fibres — activate, multiply and fuse into new fibre segments, which is genuine regeneration. But a large tear also fills with fibrous scar, and scar is stiffer than muscle and does not contract, which is why a badly rehabilitated tear leaves a permanent weak point that re-tears.

Delayed onset muscle soreness (DOMS) appears 12 to 24 hours after unaccustomed exercise, peaks at 24 to 72 hours, and resolves over 5 to 7 days.

It is not lactic acid (Chapter 1.6) — blood lactate returns to baseline within about an hour. It is microscopic damage to fibres and the connective tissue around them, and the inflammatory response to that damage. Eccentric exercise causes far more of it than concentric, because of the high forces described in Chapter 6.1.

The repeated bout effect is real and useful: after one bout of an unfamiliar exercise, the same exercise causes much less soreness for weeks afterwards. So the soreness is a one-time cost of a new movement, not an ongoing feature of training.

What actually helps is limited. Light activity, sleep and time. Massage has modest evidence. Cold water immersion reduces perceived soreness but may blunt some training adaptations, which is why it is used before competition rather than during a training block. Stretching before or after exercise does not prevent DOMS, despite being almost universally recommended for decades.

Rhabdomyolysis

Skeletal muscle breaks down and releases its contents into the bloodstream. It is one of the situations where an apparently muscular problem becomes a life-threatening internal one.

What is released, and what each does:

Myoglobin — the oxygen-storing protein (Chapter 6.1). It is filtered by the kidney, where it is directly toxic to the tubules, blocks them, and causes acute kidney injury. Myoglobin in urine turns it tea-coloured or cola-coloured, and this is the classic sign.

Potassium — muscle holds most of the body's potassium, and releasing it causes hyperkalaemia, which can stop the heart. This is the immediate threat to life.

Phosphate, which binds calcium and lowers it.

Creatine kinase (CK) — the marker used to diagnose and monitor it. Normal is under about 200 units per litre; rhabdomyolysis is usually defined as above about 1,000, and severe cases run into the tens or hundreds of thousands.

Causes:

Crush injury — the classic. And there is a specific and counter-intuitive danger here: the deterioration often happens on release, not during entrapment. While the limb is crushed, the toxic contents stay in it. When the pressure is released, they flood into the circulation at once — "crush syndrome" — and people have died shortly after being rescued from rubble. This is why fluid resuscitation is started before extrication where possible, and it is a standard principle in earthquake and building collapse response (Chapter 23.8).

Prolonged immobility — an elderly person who has fallen and lain on a hard floor for many hours, or someone unconscious from alcohol or drugs. The pressure of body weight on the dependent muscles is enough.

Extreme exertion, particularly unaccustomed intense exercise in heat, in someone unacclimatised. Military recruits and new gym attendees are the typical cases.

Heat stroke and malignant hyperthermia (Chapter 6.1).

Drugs and toxins — statins, alcohol, cocaine, amphetamines, some snake venoms.

Prolonged seizures.

Treatment centres on one thing: aggressive intravenous fluids, early and in large volume, to maintain urine flow and flush the myoglobin through before it obstructs the tubules. Delay is what causes kidney failure, and the fluid volumes required are far larger than in most other conditions. Potassium is monitored and treated urgently, and dialysis is used if kidney failure develops.

Statins and muscle

Worth its own section, because statins are among the most prescribed drugs in the world and muscle symptoms are the commonest reason people stop them.

Muscle aching affects perhaps 5 to 10 percent of statin users in clinical practice. Rhabdomyolysis is rare — roughly 1 to 3 cases per 100,000 patient-years.

And the picture is complicated by a well-documented nocebo effect. In blinded trials, muscle symptoms occur at almost the same rate on placebo as on statin. In n-of-1 trials, where individual patients alternate between statin, placebo and nothing without knowing which, most people who had stopped statins for muscle pain reported the same symptoms on placebo.

That does not mean the symptoms are imaginary — they are real experiences — but it means that in most cases the statin is not the cause, and the practical consequence is that a rechallenge, or a switch to a different statin or a lower dose, usually succeeds.

The genuine warning signs are specific: severe muscle pain with weakness, dark urine, and a markedly raised CK. Those require stopping the drug immediately.

Risk is higher with high doses, in the elderly, in kidney or liver impairment, in hypothyroidism, and — importantly — with drugs that inhibit statin metabolism. This is the CYP3A4 interaction of Chapter 1.5, and it is why grapefruit juice, some antibiotics (clarithromycin), some antifungals, and some HIV drugs matter. Chapter 22.13.

The muscular dystrophies

Inherited diseases causing progressive muscle degeneration.

Duchenne muscular dystrophy — X-linked recessive, affecting around 1 in 3,500 to 5,000 male births.

The mechanism. The dystrophin gene is the largest in the human genome, 2.4 million bases (Chapter 2.3). Dystrophin links the internal cytoskeleton of the muscle fibre to the membrane and the matrix outside, acting as a shock absorber that spreads the force of contraction. Without it, the membrane tears with every contraction, calcium leaks in, and the fibre degenerates. Muscle is progressively replaced by fat and fibrous tissue.

The course. Normal at birth. Delayed walking, then difficulty from around age 3 to 5. Gowers' sign — the child, unable to use weak hip and thigh muscles, rolls onto all fours and "walks" their hands up their legs to stand. Pseudohypertrophy of the calves, which look enlarged but are fat and fibrous tissue rather than muscle. Loss of independent walking usually by 12. Then respiratory muscle weakness and cardiomyopathy.

Historically death occurred in the late teens or twenties. With corticosteroids, non-invasive ventilation and cardiac treatment, many now live into their thirties or beyond — an outcome achieved almost entirely by supportive care rather than by curing anything.

Becker muscular dystrophy is the same gene with an in-frame deletion (Chapter 2.5), producing a shortened but partly functional dystrophin. Milder, later onset, walking preserved much longer.

Treatment is developing. Corticosteroids slow progression and are standard. Exon-skipping drugs — antisense oligonucleotides that make the splicing machinery skip a faulty exon, converting an out-of-frame deletion into an in-frame one — effectively convert Duchenne into something more like Becker. They are approved for specific mutations and their clinical benefit remains modest and debated. Gene therapy delivering a shortened "micro-dystrophin" is in trials, limited by the fact that the real gene is far too large for any viral vector (Chapter 2.9).

Myotonic dystrophy — the commonest adult-onset muscular dystrophy, caused by a repeat expansion (Chapter 2.5). Its distinctive feature is myotonia: delayed relaxation. The person grips your hand and cannot let go quickly. It is multisystem — cataracts, cardiac conduction problems, diabetes, and daytime sleepiness — and the cardiac conduction abnormalities can cause sudden death, which is why regular cardiac monitoring is part of care and why the diagnosis matters beyond the muscles.

Inflammatory myopathies

Polymyositis and dermatomyositis — autoimmune inflammation of muscle, causing symmetrical proximal weakness: difficulty rising from a chair, climbing stairs, or lifting the arms above the head, developing over weeks to months. Note the pattern — proximal, symmetrical, painless or only mildly painful, which distinguishes it from most other causes of weakness.

Dermatomyositis adds characteristic skin signs: a purple discolouration of the eyelids and a scaly rash over the knuckles.

And dermatomyositis in an adult over 40 requires a search for underlying cancer, because it is associated with malignancy in a significant minority — a paraneoplastic phenomenon in which the immune response to a tumour cross-reacts with muscle.

Inclusion body myositis is different and often misdiagnosed as polymyositis. It affects distal muscles as well, is asymmetric, and characteristically weakens finger flexion and knee extension. It occurs over 50, progresses slowly, and — importantly — does not respond to immunosuppression, so distinguishing it matters to avoid years of ineffective and toxic treatment.

Polymyalgia rheumatica is a common condition in the over-50s that is often confused with a myopathy but is not one. It causes pain and stiffness in the shoulders and hips rather than true weakness, with prolonged morning stiffness and raised inflammatory markers. It responds dramatically to low-dose steroids — often within 48 hours — and that response is so characteristic that failure to improve should prompt reconsideration of the diagnosis. It is associated with giant cell arteritis (Chapter 6.3).

Sarcopenia

Age-related loss of muscle mass and strength, and it is not merely cosmetic.

Muscle mass declines by around 3 to 8 percent per decade after 30, accelerating after 60. Strength declines faster than mass, because the loss is disproportionately in type II fibres and because the number of motor neurons falls.

The consequences are severe and cumulative: falls, fractures, loss of independence, and reduced metabolic reserve during illness. Grip strength is one of the better simple predictors of mortality in older people — not because grip matters, but because it indexes overall muscle status.

And the loss accelerates catastrophically with immobility. Complete bed rest causes 1 to 1.5 percent loss of muscle mass per day in older adults, so a two-week hospital admission can cost the equivalent of years of ageing. This is the single strongest argument for getting hospital patients out of bed, and it is why "deconditioning" is now treated as a preventable hospital-acquired harm rather than an inevitability.

Resistance training works at any age, including in people in their nineties, and trials in nursing home residents have shown measurable strength gains and improved mobility. Adequate protein intake is required alongside it — older adults need more protein per kilogram than younger ones, around 1.0 to 1.2 g/kg/day, because the muscle-building response to a given amount of protein is blunted with age. Chapter 24.6.

What Part 7 does next

The muscular and skeletal systems move the body. Everything in them depends on a delivery service that never stops. Part 7 covers the cardiovascular system: blood, the heart chamber by chamber, the electrical system and the ECG read properly, the cardiac cycle, the vessels, blood pressure control, and the circulation the fetus uses and abandons at the first breath.