(a) Enumerate various classes of antihypertensive drugs. Briefly discuss the role of calcium channel blockers in the treatment of…

(a) Antihypertensive classes and CCBs. The antihypertensive drugs can be enumerated as diuretics (thiazides, loop and potassium-sparing), angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, beta-adrenergic blockers, alpha-adrenergic blockers, centrally acting alpha-2 agonists, direct arterial vasodilators, direct renin inhibitors, and mineralocorticoid receptor antagonists. Their roles differ: diuretics reduce sodium and water retention, ACE inhibitors and ARBs reduce angiotensin II effects, beta, alpha and central agents reduce sympathetic drive, vasodilators relax arterioles, and mineralocorticoid antagonists reduce aldosterone-mediated sodium retention. In clinical practice, thiazide diuretics, ACE inhibitors, ARBs and CCBs are commonly first-line; beta blockers are preferred when angina, post-infarction state, or tachyarrhythmia coexists; alpha blockers are usually reserved for resistant hypertension or benign prostatic hyperplasia; direct vasodilators are used in resistant cases. Calcium channel blockers block L-type voltage-gated calcium channels in vascular smooth muscle, reducing calcium influx, causing relaxation, decreased systemic vascular resistance and lower blood pressure. Dihydropyridines such as amlodipine and nifedipine mainly cause peripheral vasodilation and are useful first-line agents, especially in older patients, isolated systolic hypertension and high stroke risk. Non-dihydropyridines verapamil and diltiazem also slow conduction and reduce heart rate, so they are used when angina or rate control coexists, but are less preferred as sole antihypertensives.

(b)(i) Type IV hypersensitivity and tuberculin test. Type IV hypersensitivity is a delayed, cell-mediated reaction, not antibody-mediated. Antigen is taken up by antigen-presenting cells and presented to naive CD4+ T cells; with IL-12, they differentiate into Th1 cells. Th1 cells secrete IFN-γ and IL-2; IFN-γ activates macrophages, enhances phagolysosome fusion, reactive oxygen species, MHC expression, and recruits monocytes, leading to granulomatous inflammation with epithelioid macrophages and lymphocytes. The delayed nature reflects time required for T-cell proliferation and macrophage recruitment. The reaction peaks at 48-72 hours. In tuberculin testing, 5 TU PPD is injected intradermally by the Mantoux technique; induration, not erythema, is measured. Interpretation is risk-based: ≥5 mm is positive in HIV-positive or immunocompromised persons, recent TB contacts, and those with fibrotic chest radiographs; ≥10 mm in high-risk groups such as healthcare workers, injection drug users, children under four, and residents or caregivers of high-burden settings; ≥15 mm in persons with no known risk factors. A positive test indicates prior sensitization to mycobacterial antigens, not necessarily active disease. A negative test may occur in early infection, anergy, or immunosuppression.

(b)(ii) Salmonella diseases and Widal test. Typhoidal Salmonellae, mainly S. Typhi and S. Paratyphi A, B and C, cause enteric fever, typhoid fever, paratyphoid fever, bacteremia, septicemia, and chronic gallbladder carriage. Non-typhoidal Salmonellae cause acute gastroenteritis, bacteremia, septicemia, osteomyelitis, septic arthritis, meningitis in young children, and endovascular infections. The Widal test is a slide or tube agglutination test detecting agglutinins against O (somatic) and H (flagellar) antigens. O agglutinins appear early and are mainly IgM, suggesting recent infection; H agglutinins appear later and may be IgG, persisting after past infection or vaccination. O agglutinins are generally more specific than H agglutinins; false positives may occur in malaria, dengue, typhus, sepsis, or other febrile illnesses. A single titer is not diagnostic, especially in endemic India; a fourfold rise in paired sera is significant. Commonly, O ≥1:80 or 1:160 and H ≥1:160 are considered supportive, but interpretation must be risk-based and correlated clinically. Anamnestic responses after prior infection or vaccination can cause false-positive or misleading rises.

(c) Growth disturbances and atrophy. Four disturbances of growth are hypertrophy, hyperplasia, atrophy and metaplasia. Hypertrophy is increase in cell size; hyperplasia is increase in cell number; atrophy is decrease in cell size and sometimes number; metaplasia is reversible replacement of one differentiated cell type by another. Atrophy may be physiological, such as uterine involution after pregnancy or thymic involution, or pathological, as in disuse atrophy of a limb in a cast. Atrophy occurs when a cell is smaller than normal due to decreased protein synthesis and increased protein degradation. Reduced trophic factors, denervation, ischemia, disuse, endocrine deficiency, aging, or malnutrition lower mTOR signalling and biosynthesis. Proteins are tagged by ubiquitin and degraded by the proteasome; autophagy removes damaged organelles; apoptosis may remove cells in some tissues. The cell shows shrunken cytoplasm, loss of organelles, autophagic vacuoles and lipofuscin accumulation.

(d) Tuberculous meningitis. The likely diagnosis is tuberculous meningitis. The special stain on CSF useful for confirmation is Ziehl-Neelsen acid-fast stain; the finding is acid-fast bacilli, seen as red or pink rods against a blue background. The CSF findings of lymphocytic pleocytosis, low glucose and high protein with cobweb formation support the diagnosis. Gross pathology of the affected meninges and base of brain shows a thick, opaque, gelatinous or fibrinopurulent exudate concentrated in the basal cisterns, around the optic chiasm, pituitary stalk, cranial nerves and Sylvian fissures. Small tubercles or granulomas may be seen on the meninges, with caseous necrosis. The exudate obstructs CSF flow and arachnoid granulation absorption, producing communicating hydrocephalus; vasculitis may cause infarcts, but the diagnostic gross feature is basal meningeal exudate with tubercles and hydrocephalus. Cranial nerve compression may produce optic atrophy, facial palsy, or abducens palsy.

(e) Blood group systems for identification and paternity. Blood group systems used for identification and paternity testing include ABO, Rh (D), MNSs, Kell, Duffy, Kidd, Lewis, P1PK, Hh and Xg. ABO and Rh are most important for routine identification because they are highly polymorphic and clinically significant. The other systems are useful in forensic identification, transfusion medicine and exclusion when ABO/Rh are non-informative. In paternity testing, ABO and Rh can provide exclusion when the child's genotype cannot be inherited from the alleged father; for example, a child with blood group B and a mother with group O must have received a B allele from the biological father, so an alleged father with group O is excluded, whereas an alleged father with AB, being heterozygous, can transmit B and is not excluded on this basis. When no exclusion is found, probability of paternity is calculated; HLA typing and especially DNA fingerprinting or STR analysis are now used because they give much higher discriminatory power and can establish a high probability of paternity. HLA typing is a genetic marker rather than a blood group system, and DNA fingerprinting remains the reference method for high-confidence paternity.