Inherited & metabolic liver disease flashcards
15 high-yield MRCP Part 1 cards from the Intellect Medicos Gastroenterology & Hepatology course. Try to answer each question before you open it — then study them properly with spaced repetition, which brings each card back just before you would forget it.
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A 20-year-old student becomes mildly jaundiced during a bout of flu while barely eating. Bilirubin is 45 µmol/L (unconjugated); ALT, ALP, FBC, reticulocytes and haptoglobin are normal. Urine is negative for bilirubin. What is the diagnosis and the underlying enzyme defect?
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Gilbert's syndrome – reduced activity of UDP-glucuronosyltransferase (UGT1A1).
Why? Less bilirubin is conjugated, so unconjugated bilirubin rises with fasting, illness or stress. It is benign and needs only reassurance.
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Which drug lowers bilirubin in Crigler–Najjar syndrome type II, and how?
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Phenobarbital – it induces UDP-glucuronosyltransferase activity.
Why? Type II has partial enzyme activity that can be boosted. Type I has no enzyme, so phenobarbital does not work; it needs phototherapy and liver transplant.
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Dubin–Johnson syndrome is a benign conjugated hyperbilirubinaemia caused by a defect in the ______ transporter; the liver is black on biopsy.
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MRP2 (ABCC2)
Why? Conjugated bilirubin cannot be excreted into bile. Rotor syndrome is similar but the liver is a normal colour.
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Dubin–Johnson syndrome is a benign conjugated hyperbilirubinaemia caused by a defect in the MRP2 (ABCC2) transporter; the liver is ______ on biopsy.
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black
Why? Conjugated bilirubin cannot be excreted into bile. Rotor syndrome is similar but the liver is a normal colour.
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Hereditary haemochromatosis is ______, usually due to the C282Y mutation of the HFE gene on chromosome 6.
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autosomal recessive
Why? Loss of HFE function reduces hepcidin, so the gut absorbs too much iron, which is deposited in liver, pancreas, heart, joints, pituitary and skin.
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Hereditary haemochromatosis is autosomal recessive, usually due to the ______ mutation of the HFE gene on chromosome 6.
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C282Y
Why? Loss of HFE function reduces hepcidin, so the gut absorbs too much iron, which is deposited in liver, pancreas, heart, joints, pituitary and skin.
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What is the first-line blood test for suspected hereditary haemochromatosis?
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Transferrin saturation (raised early), with serum ferritin.
Why? Transferrin saturation rises before ferritin and is not an acute-phase reactant. Confirm with HFE genotyping; screen first-degree relatives genetically.
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What is the first-line treatment of hereditary haemochromatosis, and the usual ferritin target?
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Venesection, keeping ferritin below 50 µg/L (and transferrin saturation below 50%) during maintenance.
Why? Removing blood removes iron. Desferrioxamine is second line when venesection is not possible.
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Name two complications of haemochromatosis that do NOT reverse with venesection.
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Any two of: cirrhosis, diabetes, arthropathy, hypogonadism.
Why? Fatigue, skin pigmentation, hepatomegaly, transaminitis and cardiomyopathy can improve; established fibrosis and gland destruction do not.
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Wilson's disease is an autosomal recessive defect of the copper-transporting ______ gene on chromosome 13.
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ATP7B
Why? Copper cannot be excreted in bile or loaded onto caeruloplasmin, so it builds up in liver, brain (basal ganglia), cornea and kidney.
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Wilson's disease is an autosomal recessive defect of the copper-transporting ATP7B gene on chromosome ______.
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13
Why? Copper cannot be excreted in bile or loaded onto caeruloplasmin, so it builds up in liver, brain (basal ganglia), cornea and kidney.
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Which blood and urine results support Wilson's disease?
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Low serum caeruloplasmin and raised 24-hour urinary copper.
Why? Total serum copper is often low (less caeruloplasmin-bound copper) but free copper is high. Slit-lamp shows Kayser–Fleischer rings (copper in Descemet's membrane).
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What is the first-line drug treatment of symptomatic Wilson's disease?
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A copper chelator: penicillamine or trientine.
Why? Chelators bind copper so it is excreted in urine. Zinc, which blocks gut copper absorption, is used for maintenance or presymptomatic cases.
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On liver biopsy, alpha-1 antitrypsin deficiency shows ______ globules in hepatocytes; haemochromatosis iron is shown with Perls' Prussian blue stain.
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PAS-positive, diastase-resistant
Why? The misfolded A1AT protein is trapped in the hepatocyte endoplasmic reticulum. Clinically A1AT deficiency also causes panacinar emphysema.
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On liver biopsy, alpha-1 antitrypsin deficiency shows PAS-positive, diastase-resistant globules in hepatocytes; haemochromatosis iron is shown with ______ stain.
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Perls' Prussian blue
Why? The misfolded A1AT protein is trapped in the hepatocyte endoplasmic reticulum. Clinically A1AT deficiency also causes panacinar emphysema.