Why does ketoacidosis occur in a patient whose blood glucose is very HIGH? ANSWER: because without INSULIN, cells cannot take the glucose up — so the body behaves as though it is STARVING. 1. Insulin is the signal to STORE fuel; its absence signals RELEASE. 2. Glucose is abundant in the blood but cannot enter cells. 3. The body therefore breaks down FAT for fuel. 4. KETONES accumulate as the by-product of fat breakdown. 5. The blood becomes ACIDOTIC. THE TREATMENT CONSEQUENCE: the answer is INSULIN, not simply lowering the glucose. The high glucose is a symptom of the signalling failure, not the problem itself. This is why insulin is given even when glucose is falling, and why it is not stopped as soon as the glucose normalises.

Why does acute hypoglycaemia cause loss of consciousness within minutes, when a person can fast for days without harm? ANSWER: because the brain cannot burn fat, and the ketone adaptation takes DAYS. 1. Fatty acids do not cross into the brain in useful amounts. 2. The brain stores almost no fuel of its own. 3. In PROLONGED fasting it adapts to using KETONES for much of its energy — which also spares muscle protein. 4. But that adaptation requires days to develop. 5. In ACUTE hypoglycaemia there are no ketones available and no substitute fuel. RESULT: confusion, seizure and death within MINUTES. CLINICAL CONSEQUENCE: hypoglycaemia is treated immediately, before investigation.

A malnourished, alcohol-dependent patient is found hypoglycaemic. Why must thiamine be given before or with the glucose? ANSWER: because metabolising glucose CONSUMES thiamine, and giving glucose alone can precipitate acute thiamine-deficiency encephalopathy. 1. Chronic alcohol use and poor nutrition deplete thiamine. 2. Thiamine is required to metabolise glucose. 3. A large glucose load uses up what little remains. 4. The acute neurological syndrome — confusion, eye movement abnormalities, ataxia — can be precipitated. SO: give thiamine FIRST or alongside, never glucose alone, in a malnourished or alcohol-dependent patient. This is one of the few biochemistry facts that changes what you do in the next five minutes.

A baby is normal at birth, then at three days develops poor feeding, vomiting, lethargy and seizures. Sepsis is treated but she does not improve. What should be considered, and why the delay in onset? ANSWER: an INBORN ERROR OF METABOLISM. WHY NORMAL AT BIRTH: the PLACENTA was clearing the accumulating metabolite through the mother's circulation. Delivery removes that route, and feeding supplies the substrate — so the metabolite builds up over the first days. WHY IT IS MISSED: the picture is indistinguishable from NEONATAL SEPSIS, which is far commoner. Sepsis is treated, correctly — and the metabolic cause is not considered. THE TRIGGER TO REMEMBER: consider it when a baby treated for sepsis does NOT IMPROVE as expected. TWO QUESTIONS THAT COST NOTHING: - Is there CONSANGUINITY? Most of these disorders are recessive. - Was there an unexplained NEONATAL DEATH in a previous sibling?

A patient has a macrocytic anaemia. Why must B12 be measured rather than simply giving folate? ANSWER: because folate alone corrects the ANAEMIA while allowing irreversible NEUROLOGICAL damage to continue. 1. B12 and folate deficiency both produce a macrocytic anaemia, and the blood film cannot distinguish them. 2. Only B12 deficiency damages the NERVOUS SYSTEM. 3. Giving folate improves the blood count, so the patient appears treated. 4. Meanwhile the neurological damage progresses — and it becomes PERMANENT. SO: measure BOTH before treating a macrocytic anaemia. The apparent response to folate is precisely what makes this dangerous — it removes the sign that would have prompted further investigation.

Describe the general logic of an inborn error of metabolism and how it guides treatment. ANSWER: one enzyme in a pathway is deficient, giving THREE consequences. 1. SUBSTRATE ACCUMULATES behind the block. If toxic, this is what harms the patient. 2. PRODUCT IS MISSING beyond the block. Sometimes this matters more than the accumulation. 3. ALTERNATIVE PATHWAYS open, producing metabolites that are normally negligible — often what is detected in urine and gives the diagnosis. TREATMENT FOLLOWS THE SAME THREE: RESTRICT what accumulates — dietary restriction REPLACE what is missing — supply the product REMOVE what is toxic LEARNING POINT: knowing this shape lets you reason about an unfamiliar condition, which memorising a list of named disorders does not.

Why does oedema occur in both severe liver disease and severe malnutrition, despite entirely different causes? ANSWER: both reduce plasma ALBUMIN, and albumin holds fluid inside blood vessels. 1. Albumin generates OSMOTIC PRESSURE within the vessel, opposing the hydrostatic pressure pushing fluid out. 2. In LIVER DISEASE, the liver cannot synthesise enough albumin. 3. In MALNUTRITION, there is insufficient protein intake to make it. 4. Either way, plasma albumin falls, osmotic pressure falls, and fluid leaks into the tissues. RELATED POINT ON ENZYMES: raised transaminases or amylase LOCALISE damage — hepatocytes, pancreatic acinar cells — but the HEIGHT correlates poorly with severity. A failing liver with few remaining cells may release less enzyme than a mildly injured healthy one. Interpret the pattern, not the magnitude.