NExT Pathology, Pharmacology and Microbiology (Para-clinical Sciences) Syllabus

What is amyloid, and which stain confirms it with what characteristic appearance?

Amyloid is an abnormal extracellular deposit of misfolded proteins in beta-pleated sheet configuration. Congo red stain shows apple-green birefringence under polarized light. Common types: AL (light chains, plasma cell dyscrasias) and AA (serum amyloid A, chronic inflammation).

What are Reed-Sternberg cells and which disease are they diagnostic of?

Reed-Sternberg cells are large binucleate or multinucleate cells with prominent eosinophilic nucleoli ('owl-eye' appearance), CD15+ and CD30+. They are the hallmark malignant cell of Hodgkin lymphoma.

List the indices used in classifying anemias and how MCV categorizes them.

MCV (mean corpuscular volume), MCH, MCHC, and RDW. By MCV: microcytic (<80 fL, e.g., iron deficiency, thalassemia), normocytic (80–100 fL, e.g., acute blood loss, anemia of chronic disease), and macrocytic (>100 fL, e.g., B12/folate deficiency).

What peripheral smear findings characterize iron deficiency anemia versus megaloblastic anemia?

Iron deficiency: microcytic, hypochromic RBCs with increased central pallor, anisopoikilocytosis, pencil cells, target cells. Megaloblastic anemia: macro-ovalocytes and hypersegmented neutrophils (>5 lobes).

What is the normal hemoglobin electrophoresis pattern in an adult, and what changes in beta-thalassemia major?

Normal adult: HbA (alpha2beta2) ~95–97%, HbA2 (alpha2delta2) ~2–3%, HbF (alpha2gamma2) <1%. In beta-thalassemia major: markedly reduced/absent HbA, with elevated HbF and HbA2.

Describe the extrinsic, intrinsic, and common coagulation pathways and the tests that assess them.

Extrinsic pathway (factor VII, tissue factor) is assessed by PT/INR. Intrinsic pathway (factors XII, XI, IX, VIII) is assessed by aPTT. Both converge on the common pathway (factors X, V, II/prothrombin, I/fibrinogen). Thrombin time assesses fibrinogen-to-fibrin conversion.

What clotting factors are vitamin K-dependent, and which anticoagulant inhibits them?

Factors II, VII, IX, and X (plus proteins C and S) are vitamin K-dependent (require gamma-carboxylation). Warfarin inhibits vitamin K epoxide reductase, depleting these functional factors; monitored by PT/INR.

What are the major ABO blood group compatibility rules for RBC transfusion?

Group O is the universal RBC donor (no A/B antigens); group AB is the universal recipient (no anti-A/anti-B antibodies). Recipients must not receive RBCs bearing antigens against which they have antibodies, e.g., a group A patient has anti-B antibodies and cannot receive B or AB blood.

Differentiate acute hemolytic transfusion reaction from febrile non-hemolytic transfusion reaction.

Acute hemolytic reaction: usually ABO incompatibility, complement-mediated intravascular hemolysis with fever, flank pain, hemoglobinuria, hypotension/DIC—a medical emergency. Febrile non-hemolytic reaction: most common, caused by recipient antibodies against donor leukocyte antigens/cytokines, presenting as fever/chills without hemolysis.

What casts in urinalysis indicate glomerulonephritis, acute tubular necrosis, and pyelonephritis respectively?

RBC casts indicate glomerulonephritis (glomerular bleeding). Muddy-brown granular (epithelial) casts indicate acute tubular necrosis. WBC casts indicate pyelonephritis/tubulointerstitial inflammation.

What does urine dipstick positivity for nitrites and leukocyte esterase suggest, and what is the limitation of nitrites?

Both suggest urinary tract infection: leukocyte esterase indicates pyuria (WBCs), and nitrites indicate bacteria that reduce nitrate to nitrite (e.g., E. coli, gram-negative Enterobacteriaceae). Limitation: gram-positive organisms and Pseudomonas may not reduce nitrate, giving false-negative nitrites.

Define bioavailability and first-pass metabolism.

Bioavailability (F) is the fraction of an administered dose that reaches systemic circulation unchanged; it is 100% for IV drugs. First-pass metabolism is the metabolism of an orally administered drug in the gut wall and liver before reaching systemic circulation, reducing oral bioavailability.

Give the formulas for volume of distribution, clearance, and elimination half-life.

Vd = amount of drug in body / plasma concentration. Clearance (CL) = rate of elimination / plasma concentration. Half-life t1/2 = (0.693 × Vd) / CL. Half-life determines dosing interval and time to steady state (~4–5 half-lives).

What is the difference between zero-order and first-order kinetics?

First-order kinetics: a constant fraction of drug is eliminated per unit time (rate proportional to concentration); most drugs follow this. Zero-order kinetics: a constant amount is eliminated per unit time (saturable enzymes), e.g., ethanol, phenytoin (high dose), aspirin (high dose).

Define potency versus efficacy and the meaning of ED50, LD50, and therapeutic index.

Potency is the amount of drug needed for a given effect (reflected by EC50/ED50). Efficacy is the maximal effect a drug can produce (Emax). ED50 is the dose effective in 50% of subjects; LD50 is the dose lethal in 50%. Therapeutic index = LD50/ED50; a higher TI means a safer drug.

Distinguish a competitive antagonist from a non-competitive antagonist on a dose-response curve.

A competitive (reversible) antagonist shifts the agonist dose-response curve rightward (increased EC50) but keeps Emax the same—surmountable with more agonist. A non-competitive (irreversible) antagonist reduces Emax and is not overcome by more agonist—insurmountable.

What are the WHO/Rawlins-Thompson types of adverse drug reactions (Type A and Type B)?

Type A (Augmented): dose-dependent, predictable, related to the drug's known pharmacology, common, low mortality (e.g., bleeding with warfarin). Type B (Bizarre): dose-independent, unpredictable, not related to known pharmacology, rare, higher mortality (e.g., anaphylaxis, idiosyncratic reactions).

What is pharmacovigilance and what is a 'black triangle' / yellow card concept?

Pharmacovigilance is the science of detecting, assessing, understanding, and preventing adverse drug effects. The yellow card system (and equivalents) is a spontaneous ADR reporting mechanism; the black triangle marks newer drugs under intensive/additional monitoring.

Compare the major routes of drug administration: IV, oral, and sublingual in terms of onset and first-pass effect.

IV: immediate onset, 100% bioavailability, no first-pass effect. Oral: slow/variable onset, subject to first-pass metabolism, convenient. Sublingual: rapid onset, bypasses first-pass metabolism (drains to systemic veins), e.g., glyceryl trinitrate for angina.

What is the difference between a pharmacokinetic and a pharmacodynamic drug interaction, with an example of each?

Pharmacokinetic interactions alter absorption, distribution, metabolism, or excretion (e.g., rifampin inducing CYP enzymes lowers warfarin levels). Pharmacodynamic interactions occur at the site of action without changing concentration (e.g., additive CNS depression with alcohol plus benzodiazepines).

What are the WHO criteria for a P-drug (personal drug) selection and the components of rational drug use?

WHO P-drug criteria: efficacy, safety, suitability, and cost. Rational drug use means patients receive the right medication, in the appropriate dose, for an adequate period, at the lowest cost, and matching their clinical needs.

What is the WHO Essential Medicines List and the criteria for inclusion?

The WHO Model List of Essential Medicines lists medications that satisfy the priority health-care needs of a population. Selection criteria: relevance to disease prevalence, proven efficacy and safety, and comparative cost-effectiveness; medicines should be available at all times in adequate amounts and appropriate dosage forms.

Contrast the effects of sympathetic (adrenergic) versus parasympathetic (cholinergic) stimulation on heart rate, pupils, and bronchi.

Sympathetic: increases heart rate (beta1), dilates pupils (mydriasis, alpha1), dilates bronchi (beta2). Parasympathetic: decreases heart rate (M2), constricts pupils (miosis, M3), constricts bronchi (M3).

Classify cholinergic drugs and give the antidote for organophosphate poisoning.

Cholinergics: direct-acting (e.g., pilocarpine, bethanechol) and indirect-acting cholinesterase inhibitors (reversible: neostigmine, physostigmine; irreversible: organophosphates). Organophosphate (irreversible AChE inhibitor) poisoning is treated with atropine (muscarinic antagonist) plus pralidoxime (regenerates cholinesterase if given early).

What are the main classes of antihypertensive drugs?

Diuretics (thiazides), ACE inhibitors (e.g., enalapril), angiotensin receptor blockers (e.g., losartan), calcium channel blockers (e.g., amlodipine), beta-blockers (e.g., metoprolol), and others (alpha-blockers, central agonists, direct vasodilators).

How does the mechanism of loop diuretics differ from thiazide diuretics, and where do they act?

Loop diuretics (e.g., furosemide) inhibit the Na-K-2Cl cotransporter in the thick ascending limb of the loop of Henle—most potent diuretics. Thiazides (e.g., hydrochlorothiazide) inhibit the Na-Cl cotransporter in the distal convoluted tubule—moderate efficacy and useful in hypertension.

Classify antiepileptic drugs by their primary mechanism of action.

Sodium channel blockers (phenytoin, carbamazepine, lamotrigine); GABA enhancers (benzodiazepines, barbiturates, valproate); calcium channel (T-type) blockers (ethosuximide—drug of choice for absence seizures); and multiple/novel mechanisms (levetiracetam binds SV2A, valproate has broad action).

Describe the mechanism of action of penicillins and why they don't affect human cells.

Beta-lactam antibiotics (penicillins) inhibit bacterial cell wall synthesis by binding penicillin-binding proteins (transpeptidases) and blocking peptidoglycan cross-linking; they are bactericidal. Human cells lack a peptidoglycan cell wall, so they are unaffected—providing selective toxicity.

Match antibiotic classes to their mechanisms: aminoglycosides, fluoroquinolones, macrolides, and sulfonamides.

Aminoglycosides: inhibit 30S ribosomal subunit (protein synthesis), bactericidal. Fluoroquinolones: inhibit DNA gyrase/topoisomerase. Macrolides: inhibit 50S ribosomal subunit, bacteriostatic. Sulfonamides: inhibit dihydropteroate synthase (folate synthesis), bacteriostatic.

What is the difference between Gram-positive and Gram-negative bacterial cell walls, and why do they stain differently?

Gram-positive bacteria have a thick peptidoglycan layer that retains the crystal violet–iodine complex, staining purple. Gram-negative bacteria have a thin peptidoglycan layer plus an outer lipopolysaccharide membrane; they lose the crystal violet on decolorization and take up the safranin counterstain, appearing pink/red.

Differentiate sterilization from disinfection, and name a method that achieves true sterilization including spores.

Sterilization is the complete destruction/removal of all microorganisms including bacterial spores. Disinfection eliminates most pathogenic organisms but not necessarily resistant spores. Autoclaving (moist heat at 121°C, 15 psi, 15 minutes) achieves sterilization, as do ethylene oxide gas and gamma irradiation.