Systemic Pathology: the processes behind the diagnoses
A vessel narrowed by half can occlude in minutes, while one narrowed by ninety per cent causes only angina. The difference is not the narrowing.
The first pathology chapter covered the general machinery — cell injury, inflammation, neoplasia. This one covers the specific processes that the cardiovascular and gastrointestinal chapters describe the consequences of without stopping to explain.
Cells adapt before they die
Between a normal cell and a dead one lies a set of adaptations. Recognising them explains a great deal of what is found on imaging and at post-mortem.
Hypertrophy — the cells get bigger. This is what tissue does when more work is demanded of it and its cells cannot divide. The thickened left ventricle in long-standing hypertension is hypertrophy: the muscle cannot make more cells, so it makes larger ones.
Hyperplasia — more cells, in tissue that can still divide. Benign prostatic enlargement and a goitre are hyperplasia.
Atrophy — smaller or fewer cells, when demand, blood supply or innervation is withdrawn. The wasted limb inside a cast, and the muscle wasting that follows a nerve injury.
Metaplasia — one differentiated cell type replaced by another better able to withstand the insult.
The unifying point: every one of these is reversible if the stimulus is removed. They are responses, not diseases. That is what separates them from dysplasia, which is disordered growth and genuinely premalignant — the distinction the last section of this chapter turns on.
Atheroma: rupture, not narrowing
An atheromatous plaque develops over decades: a core of lipid and inflammatory cells, covered by a fibrous cap. It narrows the vessel gradually, and for most of that time silently.
The intuitive model is that plaques grow until they block the vessel. That is not usually what happens.
What causes an acute event is rupture of the cap. The lipid core is intensely thrombogenic, and when the cap tears, blood meets it directly. Thrombosis follows within minutes.
This explains something that otherwise looks paradoxical: a modest plaque with a thin cap is more dangerous than a severe one with a thick cap. The severe stenosis causes predictable exertional angina and may be found on testing; the modest one causes nothing at all until it ruptures and kills. So a reassuring exercise test does not promise safety, and treatment aims at stabilising plaques — which is why lipid-lowering therapy reduces events out of proportion to any change in the degree of narrowing.
Virchow's triad
Thrombosis has three causes, and every risk factor you will ever be asked about fits into one of them.
Stasis. Blood that is not moving. Immobility, long journeys, a plaster cast, a fibrillating atrium that never empties properly, the pregnant uterus compressing pelvic veins.
Endothelial injury. A damaged vessel wall. Surgery, trauma, an indwelling cannula, smoking — and the ruptured plaque from the previous section, which is why arterial thrombosis and venous thrombosis share a mechanism at this level.
Hypercoagulability. Blood that clots too readily. Cancer, pregnancy, oestrogen-containing contraception, sepsis, dehydration, and inherited thrombophilias.
The practical value is that you can derive the risk assessment rather than memorising a list. Asked why a post-operative patient with cancer is at high risk, you have three separate answers: immobility, surgical injury, and the hypercoagulable state of malignancy.
💡 Exam angle: pregnancy and major surgery are the two states that hit all three arms simultaneously — which is precisely why both carry high thromboembolic risk and why prophylaxis is routine in both. If asked to explain a risk factor, name which arm of the triad it belongs to; that is what is being tested rather than the list itself.
Where an embolus goes
An embolus travels downstream until the vessel becomes too small. So the destination is determined entirely by where it started.
From a deep leg vein, blood travels to the right heart and then the lungs. Deep vein thrombosis and pulmonary embolism are therefore the same disease in two places, which is why a patient with a swollen calf and pleuritic chest pain has one diagnosis rather than two.
From the left heart or a carotid plaque, the clot enters the systemic circulation and can reach the brain, gut or a limb. This is why atrial fibrillation causes stroke — a fibrillating atrium does not empty, blood stagnates, clot forms, and it leaves through the left ventricle.
And not every embolus is clot. Fat can embolise after a long bone fracture, air after a line insertion or injury, and amniotic fluid during labour. Each produces a different clinical picture but the same principle applies — the material lodges wherever the vessels first become too small.
From irritation to cancer
Several common cancers arise through the same sequence, and knowing it explains why surveillance programmes exist and what they are looking for.
Chronic irritation → metaplasia. The tissue swaps to a cell type better able to survive the insult. Still reversible.
Irritation persists → dysplasia. Growth becomes disordered — variable cell size and shape, increased division, loss of normal architecture. This is premalignant, and it is what a surveillance programme is trying to catch.
Persists further → carcinoma in situ → invasive carcinoma. The decisive step is invasion through the basement membrane, because until then the abnormal cells cannot reach vessels or lymphatics and therefore cannot metastasise.
Three examples make the pattern concrete: smoking and the bronchus, acid reflux and the lower oesophagus — where the metaplastic change is named Barrett's oesophagus — and persistent HPV infection and the cervix, where the whole point of cervical screening is to find dysplasia before it becomes invasive.
That last example is the clearest demonstration of why the sequence matters: cervical screening works precisely because there is a long, detectable, treatable premalignant phase. A cancer with no such phase — one that goes from normal to invasive quickly — cannot be screened for in the same way, however desirable that would be. The natural history determines whether screening is possible at all, as the epidemiology chapter sets out.
Two more processes worth naming
Infarction depends on the blood supply's design. Organs supplied by a single end artery — kidney, spleen — infarct completely when it occludes. Organs with a dual supply, such as the liver and lung, tolerate occlusion better. This is the same anatomical logic as the end-artery warning about adrenaline in the anaesthesia chapter.
Granulomas mean the body could not digest something. Macrophages organise into a ball around material they cannot destroy — mycobacteria, some fungi, foreign material. Finding granulomas therefore reframes a differential entirely, which is why the finding is reported specifically rather than as "chronic inflammation".
Putting it together
Hypertrophy, hyperplasia, atrophy and metaplasia are adaptations — all reversible if the stimulus goes.
Plaque rupture causes events, not plaque size — which is why modest plaques kill and treatment aims at stabilisation.
Stasis, endothelial injury, hypercoagulability — every thrombosis risk factor fits one, and pregnancy and surgery hit all three.
An embolus lodges downstream of where it formed: leg vein to lung, left heart to brain.
Metaplasia → dysplasia → in situ → invasive, and invasion through the basement membrane is the step that matters.
A long premalignant phase is what makes screening possible at all.
No lipid targets, clotting cut-offs or surveillance intervals appear here: targets differ between guidelines, assay cut-offs are not transferable, and intervals are national policy under revision. Use your current guideline.
Syllabus points
Hypertrophy, hyperplasia, atrophy, metaplasia
All adaptations are reversible
Plaque rupture, not narrowing, causes events
Why a reassuring exercise test is not safety
Virchow's triad and deriving risk
Where an embolus lodges; DVT and PE as one disease
Metaplasia to dysplasia to invasion
Why a long premalignant phase makes screening possible
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