(a) Classify the various types of poisons. Enumerate the features of Plumbism. Discuss the tests which will show/establish the…

(a) Classification of poisons, plumbism and early tests for lead poisoning

Classification of poisons (by action): Corrosives: strong acids and alkalis (sulphuric acid, carbolic acid). Irritants: inorganic (arsenic, mercury, lead, phosphorus), organic (vegetable: castor, croton; animal: snake and insect venom) and mechanical (glass powder). Neurotics: cerebral (somniferous: opium, barbiturates; inebriant: alcohol; deliriant: datura), spinal (strychnine) and peripheral (curare). Cardiac poisons: digitalis, aconite, oleander. Asphyxiants (carbon monoxide, hydrogen sulphide) and others such as organophosphates. They are also classed by origin as inorganic, organic, gaseous or synthetic.

Features of plumbism (chronic lead poisoning): Gastrointestinal: metallic taste, anorexia, constipation and severe lead colic. Burtonian line: a blue-black line along the gum margin. Haematological: microcytic hypochromic anaemia with basophilic stippling, as lead inhibits ALA dehydratase and ferrochelatase. Neurological: peripheral neuropathy with wrist drop (extensors) and foot drop; encephalopathy with convulsions and coma, especially in children. Others: hypertension, renal tubular damage and gout, infertility and abortion, and pallor.

Tests for early poisoning: Blood lead level, the best test of recent exposure (a level above 5 μg/dL is abnormal, and above 70 μg/dL is dangerous). Zinc protoporphyrin (erythrocyte protoporphyrin), raised, reflecting exposure over the past three months. Urinary δ-aminolevulinic acid and coproporphyrin, raised. Peripheral smear showing basophilic stippling and microcytic anaemia. X-ray of long bones showing dense lead lines in children. Treatment is chelation with CaNa₂EDTA, DMSA or penicillamine.

(b)(i) Case of acute leukaemia with Auer rods

(I) Most likely diagnosis. Acute promyelocytic leukaemia (AML-M3): bleeding, bruising and fever from DIC, anaemia, leucocytosis with 75% blasts and promyelocytes carrying fine azurophilic granules and Auer rods. It is a medical emergency needing ATRA at once.

(II) Cytochemical stains. Myeloperoxidase (strongly positive), Sudan black B (positive), and naphthol AS-D chloroacetate esterase (specific esterase, positive). Non-specific esterase (alpha-naphthyl acetate) is negative or weak, and PAS is negative, which helps separate it from monocytic and lymphoid leukaemia.

(III) Favourable cytogenetics: t(15;17)(q22;q21) with the PML-RARA fusion; t(8;21) with RUNX1-RUNX1T1; inv(16) or t(16;16) with CBFB-MYH11.

(IV) Unfavourable cytogenetics: complex karyotype (three or more abnormalities); deletion 5q or monosomy 5; monosomy 7 or deletion 7q; inv(3); t(9;22); t(6;9). The variant t(11;17) (PLZF-RARA) in APL is resistant to ATRA.

(b)(ii) Rheumatic heart disease: aetiopathogenesis and microscopy

Aetiopathogenesis. Rheumatic fever follows pharyngitis by group A β-haemolytic streptococcus in children of 5 to 15 years, after a 2 to 3 week latent period. Streptococcal M-protein and carbohydrate antigens resemble heart antigens (molecular mimicry), so antibodies and CD4⁺ T cells made against the bacterium attack the heart. Genetic susceptibility (HLA-DR) and overcrowding add risk. The lesion is an immune pancarditis rather than infection.

Microscopic findings. The characteristic lesion is the Aschoff body, found in all layers of the heart: a focus of fibrinoid necrosis surrounded by lymphocytes, occasional plasma cells and plump activated macrophages, the Anitschkow cells (caterpillar or owl-eye nuclei), with some multinucleated giant cells. It heals by fibrosis. Pericardium: serofibrinous inflammation, "bread and butter" pericarditis. Myocardium: Aschoff bodies in the perivascular tissue. Endocardium: small fibrin and platelet vegetations (verrucae) along the line of closure of valves and MacCallum plaques in the left atrium. Chronic disease gives fibrous thickening and commissural fusion, fusion and shortening of the chordae, and a "fish-mouth" mitral stenosis.

(c)(i) Management of complicated Plasmodium falciparum malaria

Complicated malaria (cerebral malaria, severe anaemia, renal failure, ARDS, shock, jaundice, hypoglycaemia, acidosis) is treated in an intensive care setting. Antimalarial: intravenous artesunate 2.4 mg/kg at 0, 12 and 24 hours and then daily; once the patient can take oral drugs and after at least 24 hours, give a full three-day oral artemisinin combination (artemether-lumefantrine), and a single low dose of primaquine to clear gametocytes. If artesunate is not available, give intramuscular artemether, or intravenous quinine (20 mg/kg loading dose, then 10 mg/kg every 8 hours) with doxycycline or clindamycin; in the first trimester of pregnancy quinine with clindamycin is used. Supportive care: maintain airway, nurse the unconscious patient, control seizures with benzodiazepines, check glucose often and treat hypoglycaemia with dextrose, give fluids carefully because of the risk of pulmonary oedema, transfuse for severe anaemia (haemoglobin below 5 g/dL), give oxygen or ventilation for ARDS, and dialysis for renal failure. Treat fever with paracetamol. Corticosteroids and mannitol are harmful and should not be used. Treat suspected sepsis with antibiotics.

(c)(ii) Insulin: therapeutic indications and adverse effects

Indications: type 1 diabetes; type 2 diabetes when oral drugs fail, in pregnancy (gestational diabetes) and during infection, surgery or steroid therapy; diabetic ketoacidosis and hyperosmolar hyperglycaemic state; pancreatic diabetes; hyperkalaemia (with glucose); and parenteral nutrition. Adverse effects: hypoglycaemia, the commonest and most serious; weight gain; injection-site lipohypertrophy or lipoatrophy; local and, rarely, systemic allergy; insulin oedema; hypokalaemia; antibody formation with resistance; and the Somogyi effect (rebound hyperglycaemia after nocturnal hypoglycaemia).