Which finding marks the transition from reversible to IRREVERSIBLE cell injury? A. Cell swelling B. Fatty change C. Membrane rupture D. Reduced ATP production ANSWER: C — membrane rupture. REASONING: A, B and D are all features of the REVERSIBLE phase. Failing energy production stops the ion pumps, so the cell swells and may accumulate fat — but restoring oxygen restores the cell. Once the MEMBRANE ruptures and the nucleus breaks down, nothing recovers the cell. WHY THIS MATTERS CLINICALLY: reperfusion in myocardial infarction or stroke rescues only the cells still on the reversible side of that line. Every minute moves more cells across it — which is what "time is muscle" and "time is brain" actually mean. AND IT EXPLAINS OUR TESTS: troponin and transaminases are INTRACELLULAR molecules. They appear in blood only once membranes have failed.

Why does necrosis cause inflammation while apoptosis does not? ANSWER: because of whether cell contents ESCAPE. NECROSIS Uncontrolled. The cell swells and BURSTS. Intracellular contents spill into the tissue. The immune system has never been meant to encounter them, reads them as damage, and INFLAMMATION follows. Always pathological. APOPTOSIS Programmed. The cell dismantles itself in an orderly way and packages the fragments in MEMBRANE. Neighbouring cells clear the packages. Nothing leaks. NO inflammation. Can be entirely physiological. APOPTOSIS IS NECESSARY: it sculpts the embryo, removes worn cells, and DELETES CELLS WITH DAMAGED DNA — which is the link to neoplasia. A cell that should have been deleted and was not is allowed to divide.

A tissue sample shows lymphocytes, plasma cells and macrophages with fibrosis. Neutrophils are scanty. What does this indicate about the timing? ANSWER: a CHRONIC process — established over weeks to years, not recent. THE CELL TYPE DATES THE PROCESS: NEUTROPHILS predominant → ACUTE, recent LYMPHOCYTES, PLASMA CELLS, MACROPHAGES, with FIBROSIS → CHRONIC, established In chronic inflammation, destruction, attempted repair and fibrosis all proceed at the same time — which is why scarring accompanies it. RELATED FINDING: a GRANULOMA is macrophages organised into a ball, walling off material the body cannot digest. It is characteristic of TUBERCULOSIS and of some fungi and foreign material, and reframes the differential entirely — which is why it is reported specifically.

Which single feature proves that a tumour is malignant? A. Rapid growth B. Large size C. Metastasis D. Fixity to underlying tissue ANSWER: C — metastasis. A BENIGN TUMOUR NEVER METASTASISES. Spread to a distant site has no benign explanation, so it settles the question — even when the primary has not yet been found. A: benign tumours can grow quickly. B: size alone proves nothing; a very large tumour may be benign. D: fixity strongly SUGGESTS invasion and is a worrying sign, but inflammation can also tether tissue. THE TRAP TO AVOID: benign does NOT mean harmless. A benign tumour inside the skull kills by occupying space that cannot expand, and a benign hormone-secreting tumour kills through its secretion. "Benign" describes CELLULAR BEHAVIOUR, not clinical consequence.

A patient has a colonic carcinoma. Which organ is most likely to contain blood-borne metastases, and why? ANSWER: the LIVER. REASONING: blood-borne spread follows VENOUS DRAINAGE. The gut drains into the PORTAL VEIN, which delivers directly to the liver — so the liver is the first capillary bed the tumour cells encounter. CONTRAST: tumours draining into the systemic veins reach the right heart and then the LUNG, which is why lung is the commonest site for most other blood-borne metastases, including sarcomas. THE GENERAL PRINCIPLE: the ROUTE predicts the SITE. LYMPHATIC (typical of carcinoma) → draining nodes BLOOD-BORNE (typical of sarcoma) → liver from gut, lung from elsewhere TRANSCOELOMIC → peritoneal seeding, ascites This is why a gut primary gets liver imaging and a sarcoma gets chest imaging.

A long-term smoker's bronchial biopsy shows squamous epithelium where columnar epithelium should be. Is this cancer? ANSWER: No — this is METAPLASIA, an ADAPTATION. 1. Chronically irritated tissue may change to a cell type better able to withstand the insult. 2. Here, respiratory columnar epithelium has become squamous. 3. Metaplasia is REVERSIBLE if the irritant is removed. BUT IT IS NOT INNOCENT. Persistently irritated metaplastic tissue can progress to DYSPLASIA — disordered growth, which IS premalignant — and dysplasia can progress to carcinoma. SO THE SEQUENCE IS: chronic irritation → metaplasia → dysplasia → carcinoma This is precisely why chronic irritation is a cancer risk, and why stopping the irritant matters at the metaplastic stage.

Can a tumour marker be used to diagnose cancer? ANSWER: No. Tumour markers are for MONITORING, not diagnosis. 1. They are frequently RAISED IN BENIGN disease, so a high value does not confirm malignancy. 2. They are NORMAL in some cancers, so a normal value does not exclude it. THEIR ACTUAL VALUE: tracking a KNOWN tumour — response to treatment, and detection of recurrence, where the trend in one patient over time is informative even though the absolute number is not diagnostic. NOTE: no marker values are quoted in this chapter deliberately. Quoting one invites exactly the misuse described above, and values differ between assays in any case.