(a) (i) Describe in brief the pathogenesis and histopathological features of rheumatic heart disease. (10 marks) (ii) Enumerate…

(a)(i) Rheumatic heart disease: pathogenesis and histopathology

RHD is a late sequela of acute rheumatic fever following untreated group A beta-haemolytic Streptococcus pyogenes pharyngitis, usually after a latent period of 2–4 weeks. Pathogenesis is immune-mediated: streptococcal M protein shares epitopes with cardiac myosin, and streptococcal M protein and N-acetylglucosamine cross-react with valvular glycoproteins such as laminin and vimentin, producing molecular mimicry. Genetic susceptibility (HLA class II) contributes. T cells and antibodies cause granulomatous inflammation in the myocardium, endocardium and valves, often as pancarditis. Histologically, early lesions show Aschoff bodies—foci of fibrinoid necrosis surrounded by macrophages, including Anitschkow cells, Aschoff giant cells, lymphocytes and plasma cells. In chronic RHD, valvular fibrosis, thickening, calcification and commissural fusion occur, with mitral valve most commonly affected, followed by aortic valve, leading to stenosis and/or regurgitation.

(a)(ii) Cirrhosis: causes and histopathology

Two important causes are alcoholic liver disease and chronic viral hepatitis, especially hepatitis B and C, which are common in India. Cirrhosis is a chronic diffuse liver disease in which normal lobular architecture is replaced by fibrous septa and regenerative nodules. Key histopathological features include bridging fibrosis, distorted hepatic plates, regenerative hepatocyte nodules, loss of normal lobules, and portal tract inflammation. The fibrous septa contain inflammatory cells, bile ducts and vessels, and the regenerative nodules may be compressed. In alcoholic cirrhosis, Mallory bodies, steatosis and neutrophilic infiltration may be seen; in viral cirrhosis, interface hepatitis and lymphoplasmacytic infiltrates may predominate.

(b)(i) Celecoxib

Celecoxib is a selective COX-2 inhibitor used for rheumatoid arthritis, osteoarthritis, acute pain and familial adenomatous polyposis. Its main interactions are with warfarin and other anticoagulants, increasing bleeding risk; with ACE inhibitors, ARBs and diuretics, increasing renal impairment and hyperkalaemia; and with other NSAIDs or corticosteroids, increasing gastrointestinal and cardiovascular risk. Because COX-2 selectivity reduces but does not eliminate prostaglandin-mediated gastric protection, GI risk remains. Side effects include gastrointestinal bleeding, dyspepsia, fluid retention, hypertension, oedema, renal dysfunction, and increased cardiovascular thrombotic events such as myocardial infarction and stroke.

(b)(ii) Chloroquine

Chloroquine is an antimalarial used for clinical cure of erythrocytic stages of Plasmodium vivax and P. ovale, and for P. falciparum where sensitivity persists; radical cure of hypnozoites in vivax/ovale requires primaquine. It is also used as an amebicidal, especially for amoebic liver abscess, and immunomodulatory drug in conditions such as lupus. Important interactions: antacids and kaolin reduce its absorption, additive QT prolongation with other QT-prolonging drugs (mefloquine, amiodarone, macrolides, halofantrine), increased seizure risk with mefloquine and lowered effect of antiepileptics, and raised levels of digoxin and ciclosporin. Side effects include bull’s-eye retinopathy and corneal deposits with chronic use, QT prolongation, cardiomyopathy and conduction disturbances, nausea, pruritus, and depigmentation.

(c)(i) Giardia lamblia: disease and laboratory diagnosis

Giardia lamblia is a flagellated intestinal protozoan with pear-shaped trophozoites and oval cysts. Trophozoites attach to the duodenal and jejunal mucosa, while cysts are the infective stage passed in faeces. It causes giardiasis, a malabsorptive diarrhoeal illness with chronic watery or foul-smelling stools, steatorrhoea, abdominal cramps, bloating, flatulence, weight loss and failure to thrive in children. Laboratory diagnosis is by detecting trophozoites in duodenal aspirate or by string test, cysts in stool, antigen detection by ELISA or rapid tests, and sometimes PCR.

(c)(ii) Dengue viruses, pathogenesis and diagnosis of DHF

Dengue is caused by four serotypes, DEN-1 to DEN-4, transmitted by Aedes mosquitoes. Infection causes viraemia and immune activation. In primary infection, disease is usually mild; in secondary infection with a different serotype, pre-existing non-neutralising antibodies can bind virus and enhance entry into monocytes and macrophages through Fc receptors, causing antibody-dependent enhancement, increased viral replication, cytokine release, vascular leakage and plasma leakage. Laboratory diagnosis of dengue haemorrhagic fever includes detection of NS1 antigen or viral RNA by RT-PCR in early viraemic phase, IgM and IgG serology, and monitoring haematological markers such as thrombocytopenia and rising haematocrit indicating plasma leakage. NS1 is most useful in the first five days, while IgM appears after about five days; PCR is most sensitive early.