Medical Diagnostics

Part II · Zoology · Chapter Ten

Expect 5–8 questions: blood composition & CBC parameters, anaemia classification, ABO/Rh blood groups, coagulation tests (PT/INR, aPTT), diabetes markers (HbA1c, OGTT), imaging modalities, infectious disease diagnostics (TB, malaria, dengue, HIV), tumour markers, and HP-angle items (high-altitude polycythemia in Lahaul-Spiti, IGMC cancer registry, iodine deficiency history). Year-person-discovery facts and normal reference ranges are reliably tested.

Read · 55 min
Revise · 15 min
MCQs · 20

Syllabus Coverage

Blood composition & complete blood count • Haematology — anaemias, coagulation, blood groups • Clinical biochemistry — glucose, lipids, liver and renal function, cardiac markers • Medical imaging — X-ray, USG, CT, MRI, PET • Infectious disease diagnostics — bacterial, viral, fungal, parasitic • Non-infectious, lifestyle & genetic disorders • Tumours & cancer diagnostics.

10.1 Blood — Composition & Common Tests

Blood is a connective tissue fluid that constitutes approximately 7–8% of body weight (~5 L in an adult). It has two principal compartments: plasma (55% by volume) and the formed elements (45%), separated by centrifugation. The ratio of formed elements to total blood volume is the haematocrit (Hct).

10.1.1 Plasma

Plasma is the straw-coloured, non-cellular fraction. Its composition: water 91%, proteins 7–8%, and dissolved substances 1–2%. The three major plasma protein fractions (separated by electrophoresis) are:

Albumin (60%): maintains colloid osmotic (oncotic) pressure; transports fatty acids, bilirubin, drugs.
Globulins (35%): α₁, α₂, β, and γ fractions; γ-globulins = immunoglobulins (antibodies).
Fibrinogen (4%): soluble precursor to fibrin; essential for blood clot formation.

Plasma minus fibrinogen (and other clotting factors) is serum. Dissolved non-protein solutes include glucose, urea (BUN), creatinine, electrolytes (Na⁺, K⁺, Ca²⁺, Cl⁻, HCO₃⁻), hormones, vitamins, and dissolved gases.

Serum vs Plasma

Plasma = fluid portion of blood + all clotting factors (incl. fibrinogen), obtained by centrifuging anticoagulated blood. Serum = plasma minus fibrinogen and clotting factors, obtained by allowing blood to clot first and then centrifuging. Most biochemical tests use serum; coagulation tests require plasma.

10.1.2 Formed Elements

Three cell types are found in blood: erythrocytes (RBCs), leucocytes (WBCs), and thrombocytes (platelets). All originate from a common pluripotent stem cell (haematopoietic stem cell, HSC) in red bone marrow in adults — a process called haematopoiesis.

Fig. 10.1 Major blood cells compared. Granulocytes (neutrophil, eosinophil, basophil) have granular cytoplasm and lobed nuclei; agranulocytes (lymphocyte, monocyte) lack specific granules. Platelets are cytoplasmic fragments of megakaryocytes.

10.1.3 Complete Blood Count (CBC)

The CBC (also called Full Blood Count, FBC) is the most ordered haematological test. It is performed on an automated haematology analyser using EDTA-anticoagulated blood.

**Table 10.1**Normal CBC reference ranges (adult)
Parameter	Adult Male	Adult Female	Notes
RBC count	4.5–5.5 × 10⁶/µL	4.0–5.0 × 10⁶/µL	Lower in women, neonates high (5.0–6.5)
Haemoglobin (Hb)	13.5–17.5 g/dL	12.0–15.5 g/dL	<12 g/dL = anaemia (WHO)
Haematocrit (Hct/PCV)	41–53%	36–46%	Packed cell volume
MCV (mean cell volume)	80–100 fL		Microcytic <80; macrocytic >100
MCH (mean cell Hb)	27–33 pg		Low in iron deficiency
MCHC (mean cell Hb conc.)	32–36 g/dL		Hypochromic <32
WBC count	4,000–11,000/µL		Leukocytosis >11K; leukopenia <4K
Platelet count	1.5–4.5 × 10⁵/µL		Thrombocytopenia <1.5 L; thrombocytosis >4.5 L
Reticulocyte count	0.5–2.5%		Immature RBCs; high = active erythropoiesis

The differential WBC count (diff) gives the percentage of each leucocyte type: neutrophils 50–70%, lymphocytes 20–40%, monocytes 2–8%, eosinophils 1–4%, basophils <1%. A left shift (band neutrophils rising) indicates acute bacterial infection. Peripheral blood smear allows morphological examination — standard stains: Leishman, Giemsa, Wright.

HP Angle: Residents of Lahaul-Spiti and other high-altitude districts of HP show physiological polycythemia — elevated RBC count, Hb and Hct as a compensatory response to chronic hypoxia. This is not pathological but must be distinguished from polycythemia vera (a myeloproliferative disorder). Hb values of 17–19 g/dL in adult males are not uncommon at altitudes >4,000 m.

ABO blood groups — Landsteiner 1900 (Nobel 1930) · Rh factor — Landsteiner & Wiener 1940 · X-ray — Roentgen 1895 (Nobel 1901) · Insulin — Banting & Best 1922 (Nobel 1923) · MRI — Lauterbur & Mansfield (Nobel 2003) · ELISA — Engvall & Perlmann 1971 · PCR — Mullis 1983 (Nobel 1993)

10.2 Haematology — Counts, Smears, Coagulation

10.2.1 Anaemias

Anaemia is a reduction in haemoglobin below the normal reference range, impairing O₂ delivery. It is classified by RBC morphology (MCV-based) and by aetiology.

Anaemia types — differential diagnosis

Microcytic hypochromic (MCV <80 fL)

Iron-deficiency anaemia: Most common worldwide. Low serum ferritin, low serum iron, high TIBC, low MCV & MCH. Causes: diet, blood loss (GI, menorrhagia).
Thalassaemia: Reduced synthesis of α or β globin chains; target cells on smear; normal/high ferritin. Prevalent in Mediterranean and parts of India.
Sideroblastic anaemia: Ring sideroblasts in marrow; high serum iron.

Macrocytic / megaloblastic (MCV >100 fL)

Vitamin B₁₂ deficiency: Neurological features (subacute combined degeneration of cord). Causes: diet (strict vegan), pernicious anaemia (anti-intrinsic-factor Abs). Low serum B₁₂.
Folate deficiency: Similar blood picture but no neurological features. Common in pregnancy. Low RBC folate.
Aplastic anaemia: Pancytopenia (all three cell lines low); hypo-cellular marrow. Causes: autoimmune, radiation, drugs.

Haemolytic & Sickle-Cell Anaemia

Haemolytic anaemia

Premature destruction of RBCs. Labs: elevated unconjugated bilirubin, elevated LDH, low haptoglobin, high reticulocyte count. Causes: hereditary spherocytosis, G6PD deficiency, autoimmune haemolytic anaemia, malaria.

Sickle-cell anaemia

Point mutation in β-globin gene: Glu → Val at position 6 (A → T at DNA level). Autosomal recessive. HbS polymerises under low O₂ → sickle-shaped RBCs → vaso-occlusion, haemolysis. Heterozygotes (HbAS, sickle-cell trait) are malaria-resistant. Diagnosed by Hb electrophoresis / HPLC. Common in Africa and tribal India (Odisha, MP, Jharkhand).

Mnemonic

MIFSA for anaemia types by MCV: Microcytic = Iron def / Thalassaemia; Iso-normocytic = Folate/B₁₂ early or aplastic; and high reticulocytes = haemolytic. Or put simply: "Small RBCs need Iron; Big RBCs need B-vitamins."

10.2.2 Blood Groups — ABO and Rh

The ABO blood group system (Landsteiner, 1900) is determined by the presence or absence of A and B antigens on the RBC surface and corresponding antibodies in plasma. The ABO gene encodes a glycosyltransferase.

**Table 10.2**ABO blood group compatibility for transfusion
Blood Group	RBC Antigen	Plasma Antibody	Can donate to	Can receive from
A	A	Anti-B	A, AB	A, O
B	B	Anti-A	B, AB	B, O
AB	A and B	None	AB only	A, B, AB, O (universal recipient)
O	Neither	Anti-A and Anti-B	A, B, AB, O (universal donor)	O only

Rh factor: Presence (Rh+) or absence (Rh−) of D antigen. 85% of humans are Rh+. Universal donor: O Rh−. Universal recipient: AB Rh+. Erythroblastosis foetalis (haemolytic disease of the newborn): Rh− mother carrying Rh+ foetus; maternal anti-D IgG crosses placenta in second/subsequent pregnancies and haemolyses foetal RBCs. Prevented by injection of anti-D immunoglobulin (Rhogam) to the mother at 28 weeks and within 72 h of delivery.

10.2.3 Coagulation Cascade

Haemostasis requires three overlapping steps: (1) vascular spasm, (2) platelet plug formation (primary), and (3) coagulation (secondary haemostasis). The coagulation cascade has two initiation pathways converging on a common pathway.

Fig. 10.2 Simplified coagulation cascade. The intrinsic pathway is initiated by contact with exposed collagen (Factor XII); the extrinsic pathway is triggered by tissue factor (Factor III) released at injury. Both converge on Factor X activation. PT/INR monitors the extrinsic + common pathway (used for warfarin therapy); aPTT monitors intrinsic + common (used for heparin therapy).

Coagulation tests — what they measure

PT / INR

Prothrombin time / International Normalised Ratio. Tests extrinsic + common pathway (Factors I, II, V, VII, X). INR is standardised PT. Uses: warfarin (oral anticoagulant) monitoring; liver disease severity; pre-op screen. Normal PT ~11–13 s; INR 0.9–1.1 (therapeutic range on warfarin: 2–3).

aPTT

Activated partial thromboplastin time. Tests intrinsic + common pathway (Factors I, II, V, VIII, IX, X, XI, XII). Uses: heparin (IV anticoagulant) monitoring; haemophilia A (Factor VIII deficiency), haemophilia B (Factor IX deficiency). Normal aPTT 25–35 s. Prolonged in haemophilia and heparin therapy.

Other coagulation tests: Bleeding time (Duke/Ivy method): 2–7 min; tests platelet function + vascular response. Clotting time (Lee-White): 4–10 min; tests intrinsic pathway in glass tube. D-dimer: fibrin degradation product; elevated in DVT, PE, DIC. Fibrinogen level: normal 200–400 mg/dL; low in DIC. Platelet aggregation test: for von Willebrand disease, aspirin effect.

Exam Tip: Vitamin K is required for carboxylation of Factors II, VII, IX, and X. Warfarin is a vitamin K antagonist — it raises PT/INR. Haemophilia A (Factor VIII deficiency) is X-linked recessive; it prolongs aPTT but not PT. Royal families of Europe carried haemophilia B (Factor IX deficiency). Von Willebrand disease is the most common inherited bleeding disorder worldwide.

10.3 Clinical Biochemistry — Electrolytes, Glucose, Lipids

10.3.1 Glucose Metabolism Tests

Blood glucose regulation involves the pancreatic hormones insulin (lowers glucose) and glucagon (raises glucose). Diagnostic thresholds:

Fasting plasma glucose (FPG): Normal 70–100 mg/dL; pre-diabetes 100–125; diabetes ≥126 mg/dL on two occasions.
2-h post-load glucose (OGTT): Oral glucose tolerance test — 75 g glucose load. Normal <140 mg/dL; pre-diabetes 140–199; diabetes ≥200 mg/dL.
Random plasma glucose: Diabetes ≥200 mg/dL with symptoms.
HbA1c (glycated haemoglobin): Reflects average plasma glucose over 3 months (RBC lifespan ~120 days). Normal <5.7%; pre-diabetes 5.7–6.4%; diabetes ≥6.5%. Each 1% change in HbA1c ≈ 30 mg/dL change in mean glucose. Used for monitoring, not diagnosis in all guidelines.

Type 1 vs Type 2 Diabetes Mellitus

Type 1 (IDDM)

Autoimmune destruction of pancreatic β-cells → absolute insulin deficiency. Onset: childhood/adolescence. Thin patients. Antibodies: anti-GAD, anti-islet. Requires insulin therapy. Prone to diabetic ketoacidosis (DKA). HLA-DR3/DR4 association.

Type 2 (NIDDM)

Insulin resistance + progressive β-cell exhaustion. Onset: adult (>40 yrs, increasingly younger). Associated with obesity, sedentary lifestyle, family history. Managed with lifestyle changes, oral hypoglycaemics (metformin first-line), +/− insulin. Prone to hyperosmolar hyperglycaemic state (HHS). No specific antibodies.

**Table 10.3**Diabetes monitoring tests and targets
Test	Normal	Pre-diabetes	Diabetes (diagnosis)
Fasting plasma glucose	<100 mg/dL	100–125 mg/dL	≥126 mg/dL (×2)
2-h OGTT (75 g)	<140 mg/dL	140–199 mg/dL	≥200 mg/dL
HbA1c	<5.7%	5.7–6.4%	≥6.5%
Random glucose (with symptoms)	—	—	≥200 mg/dL

Complications of diabetes — Microvascular: diabetic retinopathy (commonest cause of new blindness in working-age adults), diabetic nephropathy (CKD; albuminuria is earliest marker), diabetic neuropathy (stocking-glove sensory loss). Macrovascular: atherosclerosis leading to MI, stroke, peripheral artery disease.

10.3.2 Lipid Panel

The lipid profile (fasting 9–12 h) includes: Total cholesterol, HDL-C, LDL-C (calculated via Friedewald formula), and triglycerides (TG). Cardiovascular risk stratification depends on LDL and the TC:HDL ratio.

HDL vs LDL cholesterol

HDL — "Good" Cholesterol

High-density lipoprotein. Transports cholesterol from peripheral tissues to liver for excretion (reverse cholesterol transport). Protective against atherosclerosis. Target: >40 mg/dL (men); >50 mg/dL (women). Raised by exercise, niacin, oestrogens.

LDL — "Bad" Cholesterol

Low-density lipoprotein. Deposits cholesterol in arterial walls → atherosclerotic plaques. Target: <100 mg/dL (general); <70 mg/dL (high-risk: post-MI, diabetes). Lowered by statins (HMG-CoA reductase inhibitors). Elevated LDL increases coronary artery disease risk.

Normal lipid targets: Total cholesterol <200 mg/dL (desirable); 200–239 (borderline high); ≥240 (high). Triglycerides normal <150 mg/dL; borderline 150–199; high 200–499; very high ≥500 (pancreatitis risk). Metabolic syndrome criteria include: central obesity (waist >102 cm men; >88 cm women), TG ≥150, HDL low, BP ≥130/85, FPG ≥100 mg/dL (any 3 of 5).

10.3.3 Electrolytes and Renal Function

Serum electrolyte panel: Na⁺ (normal 135–145 mEq/L), K⁺ (3.5–5.0), Cl⁻ (98–106), HCO₃⁻ (22–29), Ca²⁺ (8.5–10.5 mg/dL). Renal function tests: serum creatinine (normal 0.6–1.2 mg/dL in men; 0.5–1.1 in women); BUN (blood urea nitrogen, 7–20 mg/dL); BUN:creatinine ratio (10–20 normal; >20 pre-renal; <10 intrinsic renal disease); eGFR (estimated glomerular filtration rate; ≥90 mL/min/1.73 m² normal; <60 = CKD). Earliest marker of diabetic nephropathy: microalbuminuria (30–300 mg/day).

10.3.4 Liver Function Tests (LFT)

Key LFT parameters: ALT (alanine aminotransferase, liver-specific): normal <40 U/L; elevated in hepatocellular damage. AST (aspartate aminotransferase): also in heart, muscle. ALP (alkaline phosphatase): elevated in cholestasis and bone disease. Total bilirubin: normal <1.2 mg/dL (direct conjugated <0.3; indirect unconjugated <0.8). Albumin: marker of hepatic synthetic function; low in chronic liver disease. PT/INR: elevated in acute liver failure (liver makes clotting factors).

Jaundice classification

Pre-hepatic (haemolytic)

Excess bilirubin from haemolysis. Unconjugated (indirect) bilirubin elevated. Urine normal colour; stool normal. LFT normal (liver overwhelmed). E.g. sickle-cell crisis, thalassaemia, haemolytic anaemia.

Hepatic

Hepatocellular damage. Both conjugated and unconjugated bilirubin elevated. ALT and AST markedly high. Dark urine (bilirubinuria). E.g. viral hepatitis, cirrhosis, drug toxicity.

Post-hepatic (obstructive) jaundice: Bile duct obstruction (gallstones, cholangiocarcinoma, pancreatic cancer). Conjugated (direct) bilirubin markedly elevated. ALP and GGT elevated. Dark urine + pale/clay-coloured stools. Pruritus (bile salt deposition in skin).

10.3.5 Cardiac Markers

Used to diagnose acute myocardial infarction (AMI): Troponin I/T — most sensitive and specific; rises 3–6 h post-MI, peaks 12–24 h, stays elevated 7–14 days. High-sensitivity troponin (hs-cTn) can detect MI at 1 h (ESC 0h/1h algorithm). CK-MB (creatine kinase myocardial band): rises 3–8 h, normalises in 48–72 h; used to detect reinfarction. Myoglobin: earliest (1–3 h) but not cardiac-specific. BNP/NT-proBNP (brain natriuretic peptide): marker of ventricular stretch → used in heart failure diagnosis and monitoring.

Cardiac troponin first used clinically — Cummins et al. 1987 · HbA1c as diabetes monitor — established 1970s (Koenig et al. 1976) · ECG — Einthoven 1902 (Nobel 1924) · Ultrasound (medical) — Wild & Reid 1952; cardiac echo — Edler & Hertz 1954

10.4 Imaging — X-ray, USG, CT, MRI, PET

Medical imaging allows non-invasive visualisation of internal structures. The five modalities tested in HPRCA differ in their physical principle, radiation exposure, cost, and clinical application.

CT vs MRI vs PET vs USG — key contrasts

CT Scan

Computed Tomography. Multiple X-rays + computer reconstruction (Hounsfield & Cormack, Nobel 1979). Ionising radiation (higher dose than plain X-ray). Excellent for bone, lung, acute haemorrhage. Contrast agents (iodine-based) enhance vessels/tumours. Fast (seconds). Hounsfield units (HU) quantify tissue density: bone ~+400 to +1000 HU; water 0 HU; fat −100 HU; air −1000 HU.

MRI

Magnetic Resonance Imaging. Uses strong magnetic field + radiofrequency pulses → proton (H⁺) relaxation signals. No ionising radiation. Nobel 2003: Lauterbur & Mansfield. Superior soft tissue contrast (brain, spinal cord, joints, liver). T1-weighted: fat bright, water dark; T2-weighted: water bright (best for oedema, tumour). Contraindicated with ferromagnetic implants. Slow, noisy, expensive.

X-ray vs Ultrasound vs PET

X-ray (Radiography)

Roentgen 1895 (Nobel 1901). Ionising radiation. Dense structures attenuate more → bone = white; lung air = black; soft tissue = grey. Chest X-ray: pneumonia, pneumothorax, fractures, TB (apical opacity, cavitation). Cheap, rapid, widely available. Limited for soft tissue detail.

Ultrasound (USG)

No ionising radiation. High-frequency sound waves (2–18 MHz) reflected at tissue interfaces. Real-time, portable, inexpensive. Ideal: abdomen (liver, gallbladder, kidneys, spleen), obstetric (foetal well-being, anomaly scan), echocardiography, guided procedures. Doppler USG: blood flow velocity (DVT, valvular disease). Limitation: poor penetration through bone and gas-filled structures.

PET (Positron Emission Tomography)

Functional/metabolic imaging. Radiotracer injected — typically ¹⁸F-FDG (fluorodeoxyglucose, F-18 labelled). Tumour cells have high glucose uptake → light up on PET. Positrons emitted annihilate with electrons → two 511 keV gamma rays detected. PET-CT combines anatomical + metabolic information. Uses: cancer staging, treatment response, brain metabolism (Alzheimer's), myocardial viability. Ionising radiation. Very expensive. Radiotracer half-life short (~110 min for F-18).

Nuclear Medicine (Scintigraphy)

Technetium-99m (^99mTc) most commonly used radionuclide. Bone scans (metastasis detection), thyroid scans (hot/cold nodules), renal scans (GFR, obstruction). SPECT = single-photon emission CT. Ionising but low dose.

Fig. 10.3 Imaging modality decision tree. Bone and chest pathology: X-ray first. CNS and soft tissue: MRI preferred (no ionising radiation). Abdominal and obstetric: USG (safe in pregnancy). Cancer staging: PET-CT for metabolic-anatomical correlation.

Exam Tip: MRI does not use X-rays or radiation — it uses magnetic fields and radio waves. USG also has zero ionising radiation. CT gives the highest radiation dose of commonly used modalities. PET requires a radioactive tracer but the gamma dose is relatively low. Contraindications to MRI: cardiac pacemakers, cochlear implants, and ferromagnetic metal implants.

10.5 Infectious Diseases — Bacterial, Viral, Fungal, Parasitic Diagnostics

10.5.1 Bacterial Diagnostics

Gram stain (H. C. Gram, 1884): rapid presumptive identification in <30 min. Gram-positive bacteria retain crystal violet (purple); Gram-negative bacteria stain safranin (pink) after decolourisation. Identifies morphology (cocci, rods) and guides empiric antibiotic choice.

Culture: gold standard for definitive identification. Blood agar: most bacteria; MacConkey agar (MAC): Gram-negative enteric rods; Lowenstein-Jensen (LJ) medium: Mycobacterium tuberculosis (slow-growing, 4–8 weeks); EMB agar (eosin methylene blue): Gram-negative; TCBS agar: Vibrio cholerae; Thayer-Martin: Neisseria gonorrhoeae.

Antibiotic sensitivity testing: Kirby-Bauer disk diffusion (zone of inhibition measured against standard); Minimum Inhibitory Concentration (MIC) by broth microdilution or E-test strip; automated systems (VITEK, Phoenix).

Special stains: Ziehl-Neelsen (ZN) — acid-fast bacilli (AFB); M. tuberculosis appears red on blue background. GeneXpert MTB/RIF: rapid PCR-based test for TB and rifampicin resistance in <2 h. Mantoux test (tuberculin skin test, TST): intradermal PPD injection; positive ≥10 mm induration at 48–72 h in general population. IGRA (Interferon-Gamma Release Assay, QuantiFERON-TB Gold): blood test; less affected by BCG vaccination.

Bacterial vs Viral diagnostic methods

Bacterial infections

Culture: definitive ID, antibiotic sensitivities (24–72 h)
Gram stain: rapid morphology (<1 h)
PCR: rapid, highly sensitive (GeneXpert TB, STI panels)
Serology: Widal test (typhoid; H and O agglutinins); ASO titre (Streptococcus); brucella agglutination
Antigen tests: urinary antigen for Legionella, S. pneumoniae
Biochemical ID: API strips, MALDI-TOF mass spectrometry

Viral infections

RT-PCR: gold standard for RNA viruses (SARS-CoV-2, HIV, dengue, influenza)
ELISA (Engvall & Perlmann, 1971): antigen or antibody detection; HIV Ab/Ag (4th gen), HBsAg, anti-HCV, dengue NS1
Rapid Antigen Test (RAT): SARS-CoV-2, influenza — quick but less sensitive
Serology: IgM = acute/recent infection; IgG = past infection or immunity; TORCH panel
Viral culture: cell lines (BSL-2/3 labs); slow, rarely done clinically
Electron microscopy: morphology of novel viruses (rare use)

10.5.2 Major Infectious Diseases and Their Diagnostics

HIV/AIDS: HIV-1 and HIV-2 retroviruses; target CD4+ T-helper cells. 4th-generation ELISA (detects both HIV antibody AND p24 antigen, window period reduced to ~18 days). Confirmatory: Western blot or HIV RNA PCR. CD4 count monitors immune status (normal >500/µL; AIDS <200/µL). Viral load (HIV RNA copies/mL) monitors treatment. NACO (India) guidelines: test by ELISA, confirm by western blot, then start ART regardless of CD4 count.

Tuberculosis (M. tuberculosis, AFB): ZN stain, LJ culture, Mantoux, GeneXpert MTB/RIF (detects TB + rifampicin resistance), IGRA. Chest X-ray: upper lobe infiltrates, cavitation, pleural effusion. DOTS (Directly Observed Treatment Short-course) national programme.

Malaria (Plasmodium falciparum, vivax, malariae, ovale): Peripheral blood smear (thick + thin; Giemsa stain) — gold standard; identifies species and stage. Rapid Diagnostic Test (RDT/ICT): detects HRP-2 (P. falciparum) or pLDH (pan-Plasmodium); 15 min. PCR for species confirmation and drug resistance research.

Dengue: Flavivirus; Aedes mosquito. Day 1–5 of fever: NS1 antigen test (highly sensitive). After day 5: IgM antibody (ELISA). IgG indicates past infection or secondary dengue. RT-PCR for serotype identification. CBC: thrombocytopenia + leucopenia characteristic. Platelet count <1 lakh → watch carefully; <20,000 → severe dengue.

Typhoid (Salmonella typhi): Widal test (serological, O and H agglutinins; fourfold rise diagnostic); Typhi-dot (IgM dot ELISA, rapid); blood culture — gold standard (positive in 70–80% of first week).

Hepatitis A vs B vs C vs D vs E

Hepatitis A & E (faeco-oral)

Hep A: RNA picornavirus. Faecal-oral transmission. Self-limiting; no chronicity. Diagnosis: IgM anti-HAV (acute). Vaccine available. Common in poor sanitation areas.

Hep E: RNA hepevirus. Similar transmission. High mortality in pregnant women (15–25%). No reliable commercial vaccine (India). Common in HP/Uttarakhand waterborne outbreaks.

Hepatitis B, C, D (blood-borne)

Hep B: DNA hepadnavirus. HBsAg = surface antigen (marker of infection); anti-HBs = immunity; HBeAg = high infectivity; anti-HBc IgM = acute; PCR = HBV DNA viral load. Vaccine available (3-dose). Can become chronic (10% adults). HP has endemic patches especially in certain tribal communities.

Hep C: RNA flavivirus. No vaccine. Chronic in 70–80%. Anti-HCV antibody (ELISA); confirmatory HCV RNA PCR. Direct-acting antivirals (DAAs) now cure >95%.

Hep D: defective RNA virus; requires HBV co-infection.

SARS-CoV-2 / COVID-19: (+)ssRNA betacoronavirus. Diagnostic methods: RT-PCR (nasopharyngeal swab; gold standard; sensitivity 70–85%), RAT (rapid antigen; 15–30 min; lower sensitivity, useful for mass screening), antibody testing (IgG/IgM; useful epidemiologically, not for acute diagnosis), LFT/CBC abnormalities (lymphopenia, elevated CRP, LDH, ferritin, D-dimer in severe disease).

10.5.3 Fungal and Parasitic Diagnostics

Fungal infections: KOH (potassium hydroxide) wet mount — rapid; dissolves keratin, leaving fungal hyphae/spores visible. Sabouraud dextrose agar — standard culture medium. India ink preparation (CSF) — Cryptococcus. Galactomannan antigen (serum/BAL) — invasive Aspergillosis. Beta-D-glucan — pan-fungal marker. Histoplasma urine antigen test.

Parasitic infections: Stool microscopy (ova and cyst examination, Kato-Katz for helminths); peripheral blood smear — malaria parasite; Knott's concentration for microfilariae; ICT (immunochromatographic test) for filariasis; serological tests (ELISA) for toxoplasmosis, hydatid, cysticercosis; PCR for leishmaniasis (rK39 antigen strip test for visceral leishmaniasis / kala-azar).

HP Angle: Brucellosis is an occupational hazard for livestock workers, veterinarians, and slaughterhouse workers in HP, especially in Kullu, Kangra, and Chamba districts where cattle and sheep farming are prevalent. Diagnosis: Brucella agglutination test (Standard Agglutination Test, SAT; titre ≥1:160 significant) or blood culture (BACTEC system). Zoonotic disease — Brucella abortus (cattle), B. melitensis (goats/sheep), B. suis (pigs). HP Animal Husbandry Department runs brucellosis control programmes.

Mnemonic

ELISA stands for Enzyme-Linked ImmunoSorbent Assay. Remember: HIV Western blot confirms what ELISA screens. "ELISA screens, Western blot confirms, PCR quantifies." For malaria: "Smear sees species; RDT detects HRP-2 for falciparum fast."

10.6 Non-Infectious, Lifestyle & Genetic Disorders

10.6.1 Hypertension

Hypertension (HTN) = persistently elevated blood pressure. Diagnosed by sphygmomanometer (Korotkoff sounds). JNC 8 / ACC-AHA 2017 categories: Normal <120/80 mmHg; Elevated 120–129/<80; Stage 1 HTN 130–139/80–89; Stage 2 HTN ≥140/90; Hypertensive crisis >180/120 mmHg. WHO definition of hypertension: ≥140/90 mmHg. Primary (essential) HTN: >90% of cases; no identifiable cause; polygenic + environmental (salt, obesity, stress). Secondary HTN: renal artery stenosis, phaeochromocytoma, Cushing's syndrome, primary hyperaldosteronism.

Systolic vs Diastolic hypertension

Systolic BP (SBP)

Peak arterial pressure during ventricular contraction. Rises progressively with age due to arterial stiffness. Isolated systolic hypertension (ISH): SBP ≥140 + DBP <90; common in elderly; major risk for stroke. SBP is a stronger predictor of cardiovascular events than DBP in patients >50 years.

Diastolic BP (DBP)

Arterial pressure during ventricular relaxation (filling phase). Primarily reflects peripheral vascular resistance. Elevated DBP in younger patients indicates high total peripheral resistance. Pulse pressure = SBP − DBP (normal 40 mmHg); widened >60 = aortic regurgitation, hyperthyroidism, fever; narrowed <25 = cardiac tamponade, severe heart failure.

10.6.2 ECG

Electrocardiogram (Einthoven, 1902; Nobel 1924) records electrical activity of the heart. 12-lead ECG is standard. Key waveforms:

**Table 10.4**ECG wave morphology and clinical significance
Wave / Interval	Represents	Normal Duration	Abnormality
P wave	Atrial depolarisation (SA node → atria)	<120 ms; <2.5 mm	Absent in AF; broad in left atrial enlargement
PR interval	AV nodal conduction delay	120–200 ms	Prolonged: 1st-degree AV block; short: WPW syndrome
QRS complex	Ventricular depolarisation	<120 ms	Wide >120 ms: bundle branch block, VT
ST segment	Ventricular plateau (no net current)	Isoelectric	Elevation: STEMI; Depression: NSTEMI, ischaemia
T wave	Ventricular repolarisation	Asymmetric, upright	Inverted: ischaemia, RVH; peaked: hyperkalaemia
QT interval	Total ventricular electrical activity	QTc <440 ms (men); <460 ms (women)	Prolonged: torsades de pointes risk (drugs, electrolytes)

10.6.3 Obesity and Metabolic Syndrome

Body Mass Index (BMI) = weight(kg) / height(m)². WHO categories: Underweight <18.5; Normal 18.5–24.9; Overweight 25–29.9; Obese Class I 30–34.9; Class II 35–39.9; Class III (morbid) ≥40. Indian-specific cut-offs for metabolic risk are lower: overweight ≥23; obese ≥25 kg/m². Waist circumference is a better predictor of central adiposity (abdominal obesity >90 cm men; >80 cm women in Asians).

10.6.4 Thyroid Disorders

TSH (thyroid-stimulating hormone): most sensitive screening test for thyroid dysfunction. Normal 0.4–4.0 mIU/L. Elevated TSH = hypothyroidism (TSH high, T4 low); suppressed TSH = hyperthyroidism (TSH low, T4/T3 high). Free T4 (fT4) and free T3 (fT3) are the active hormone fractions. Anti-TPO antibodies: Hashimoto's thyroiditis. TSH receptor antibodies (TSHRAb/TRAB): Graves' disease (stimulating). Thyroid function tests (TFT): TSH + fT4 is the standard first-line panel.

HP Angle: Iodine deficiency disorder (IDD) causing goitre was historically prevalent in the sub-Himalayan belt including HP districts such as Shimla, Mandi, Solan, and Sirmaur. Universal salt iodisation under the National Iodine Deficiency Disorders Control Programme (NIDDCP) has largely eliminated endemic goitre, but pockets remain. Iodine deficiency during pregnancy causes cretinism (intellectual disability in children). Urinary iodine excretion (UIE) is the population-level biomarker; median UIE <100 µg/L indicates deficiency.

10.6.5 Genetic Diagnostic Tests

Karyotype: G-banding of chromosomes from cultured lymphocytes; detects chromosomal number abnormalities (Down syndrome — trisomy 21; Turner — 45,X; Klinefelter — 47,XXY) and large structural rearrangements. FISH (Fluorescence In Situ Hybridisation): detects specific chromosomal regions with fluorescent probes; rapid results (24 h), useful in haematological cancers (BCR-ABL in CML). PCR: amplification of specific gene regions; used to confirm point mutations (sickle cell Hb, cystic fibrosis ΔF508, factor V Leiden). NGS (next-generation sequencing): whole-exome (WES) or whole-genome (WGS) sequencing; detects rare/novel mutations; increasingly used in inherited disease diagnosis and cancer genomics.

Prenatal genetic testing: Amniocentesis (14–16 weeks): amniotic fluid for foetal karyotype, AFP level (elevated in neural tube defects), chromosome microarray. CVS (chorionic villus sampling, 10–13 weeks): earlier but slightly higher miscarriage risk. NIPT (non-invasive prenatal testing): cell-free foetal DNA in maternal blood; screens for trisomies 21, 18, 13 and sex-chromosome aneuploidy; high sensitivity (>99% for T21). All prenatal sex determination testing for non-medical purposes is illegal under the PC-PNDT Act in India.

10.7 Tumours & Cancer Diagnostics

10.7.1 Benign vs Malignant Tumours

A tumour (neoplasm) is an abnormal, uncontrolled proliferation of cells. The fundamental classification is:

Benign vs Malignant tumour

Benign tumour

Well-differentiated cells resembling tissue of origin. Grows slowly, encapsulated, does not invade surrounding tissues. No metastasis. Rarely life-threatening unless it compresses critical structures (e.g., brain meningioma). Examples: lipoma (fat), adenoma (gland), fibroma (fibrous tissue), leiomyoma/fibroid (smooth muscle), papilloma (epithelium). Naming: tissue type + suffix “-oma”.

Malignant tumour (Cancer)

Poorly differentiated (anaplastic). Grows rapidly, invasive — breaches basement membrane; metastasises via blood or lymphatics to distant organs. Can be life-threatening. Hallmarks of cancer (Hanahan & Weinberg): sustained proliferative signalling, evasion of growth suppressors, resistance to apoptosis, replicative immortality, angiogenesis, invasion & metastasis, reprogramming energy metabolism, evading immune destruction. Named by tissue of origin + “carcinoma” or “sarcoma”.

10.7.2 Cancer Classification

Carcinoma vs Sarcoma vs Leukaemia vs Lymphoma

Carcinoma

Malignancy of epithelial cells. Most common cancer type (>85% of all cancers). Sub-types: adenocarcinoma (glandular epithelium — colon, breast, lung, prostate), squamous cell carcinoma (stratified squamous — lung, oesophagus, cervix, head & neck), basal cell carcinoma (skin, rarely metastasises), transitional cell carcinoma (bladder). Metastasises primarily via lymphatics first.

Sarcoma

Malignancy of connective/mesenchymal tissue: bone (osteosarcoma), cartilage (chondrosarcoma), muscle (rhabdomyosarcoma — skeletal; leiomyosarcoma — smooth), fat (liposarcoma), blood vessels (angiosarcoma). Rarer (<1% of cancers in adults). Metastasises primarily via blood (haematogenous) to lungs.

Leukaemia

Malignancy of bone marrow / blood. Classified by cell lineage and speed: ALL (acute lymphoblastic — most common childhood cancer); AML (acute myeloid — adults); CLL (chronic lymphocytic — commonest adult leukaemia in West); CML (chronic myeloid — Philadelphia chromosome, BCR-ABL, treated with imatinib). Presents with pancytopenia, anaemia, infections, bleeding. Diagnosed by peripheral blood smear + bone marrow biopsy.

Lymphoma

Malignancy of lymphoid tissue (lymph nodes, spleen, MALT). Hodgkin's lymphoma (HL): Reed-Sternberg cells (owl-eye nuclei) pathognomonic; predictable spread; highly curable (cure rate 80–90%). Non-Hodgkin's lymphoma (NHL): heterogeneous group; B-cell (diffuse large B-cell, follicular) or T-cell; less predictable spread. Diagnosed by lymph node biopsy + IHC.

10.7.3 TNM Staging

The TNM system (AJCC/UICC) is the universal staging framework: T = primary Tumour size/invasion (T0–T4); N = regional lymph Node involvement (N0–N3); M = distant Metastasis (M0 = none; M1 = present). Combined into Stage I (localised) to Stage IV (metastatic). Stage determines prognosis and treatment strategy.

10.7.4 Tumour Markers

Tumour markers are substances (proteins, hormones, enzymes, genes) produced by tumour cells or by the body in response to tumour cells, measurable in blood/serum. They are primarily used for monitoring treatment response and detecting recurrence — not screening (except PSA and AFP in selected contexts).

**Table 10.5**Widely used tumour markers
Marker	Full Name	Cancer Association	Notes
PSA	Prostate-Specific Antigen	Prostate cancer	Also elevated in BPH, prostatitis. Screening controversial. Normal <4 ng/mL.
CEA	Carcinoembryonic Antigen	Colorectal cancer (also lung, breast, gastric)	Foetal protein re-expressed in cancer. Not screening tool; used for monitoring. Normal <5 ng/mL (non-smoker).
AFP	Alpha-fetoprotein	Hepatocellular carcinoma (HCC); testicular germ-cell tumours	Foetal liver protein. Also elevated in yolk-sac tumours. Used in liver disease surveillance.
CA-125	Cancer Antigen 125 / MUC16	Ovarian cancer	Not specific — elevated in endometriosis, peritoneal inflammation. Monitor treatment response.
CA 19-9	Carbohydrate Antigen 19-9	Pancreatic cancer; cholangiocarcinoma	Lewis antigen; undetectable in Lewis-negative individuals. Used for monitoring, not screening.
βhCG	beta-human Chorionic Gonadotrophin	Gestational trophoblastic disease; testicular choriocarcinoma	Also rises in pregnancy. Also a sensitive pregnancy test.
LDH	Lactate Dehydrogenase	Non-specific; lymphoma, testicular cancer, haemolysis	Reflects tumour bulk and turnover. Poor specificity but prognostic in some cancers.
Calcitonin	Calcitonin	Medullary thyroid carcinoma (MTC)	From parafollicular C-cells. Also used for screening in MEN-2 families.

10.7.5 Histopathology, Biopsy and Cytology

Biopsy: tissue removal for histopathological examination — definitive diagnosis. Types: incisional (partial), excisional (complete), core needle biopsy (CNB), punch biopsy (skin). Tissue processed: fixation in formalin → paraffin embedding → sectioning → staining (H&E standard). Frozen section: intraoperative rapid diagnosis (<20 min). FNAC (fine-needle aspiration cytology): cytological (not histological) diagnosis; cells aspirated by fine needle; less invasive but limited by sampling and no tissue architecture.

Immunohistochemistry (IHC): antibodies detect specific proteins in tissue sections. Tumour typing: ER/PR/HER2 in breast cancer; Ki-67 (proliferation index); CK (cytokeratin — carcinoma), vimentin (sarcoma), CD markers (leukaemia/lymphoma), S100 (melanoma, neural). Liquid biopsy: detection of circulating tumour DNA (ctDNA) or circulating tumour cells (CTCs) in blood; non-invasive, can monitor for minimal residual disease and emergence of resistance mutations. NGS panels (e.g., FoundationOne CDx): detect actionable mutations for targeted therapy selection.

HP Angle: The Indira Gandhi Medical College (IGMC), Shimla is the main tertiary referral centre in HP and hosts the HP Cancer Registry (a Population-Based Cancer Registry, PBCR) as part of the National Cancer Registry Programme (NCRP). Data from the IGMC PBCR shows oral cancer (tobacco chewing, reverse smoking in some districts), cervical cancer, lung and oesophageal cancers among the leading types in HP. Cancer screening camps under the National Programme for Prevention & Control of Cancer, Diabetes, CVD & Stroke (NPCDCS) are run at district hospitals across HP.

Worked example — classify a tumour from given features

"A 55-year-old woman presents with a rapidly growing, painful mass in her right thigh. Biopsy shows spindle-shaped cells with frequent mitoses, surrounded by collagen fibres. No epithelial markers (CK-negative). Vimentin-positive."

Strategy: (i) Spindle-cell morphology + collagen = mesenchymal origin; (ii) CK− rules out carcinoma; (iii) vimentin+ confirms mesenchymal/connective tissue; (iv) rapid growth, mitoses = malignant; (v) soft tissue location → likely sarcoma. Spindle cells in fibrous stroma → most consistent with fibrosarcoma or undifferentiated pleomorphic sarcoma. Answer: Malignant mesenchymal tumour (sarcoma), not carcinoma.

Worked example — pick correct test for given symptom

"A 28-year-old healthcare worker has fever, night sweats, and cough for 3 weeks. Chest X-ray shows right upper lobe opacity. Which single test has the best sensitivity AND specificity for definitive diagnosis?"

Strategy: Clinical + CXR strongly suggests pulmonary TB. Tests: (i) Sputum ZN stain — rapid but only 30–60% sensitive; (ii) Mantoux — indicates exposure, not active disease; (iii) IGRA — similar to Mantoux, exposure not disease; (iv) LJ culture — gold standard sensitivity/specificity but 4–8 weeks; (v) GeneXpert MTB/RIF — >88% sensitivity, >99% specificity, result in 2 hours, also detects rifampicin resistance. Answer: GeneXpert MTB/RIF is the best single test (per RNTCP/NTEP guidelines, India).

Worked example — interpret a CBC report

"CBC report: Hb 8.2 g/dL; MCV 70 fL; MCH 21 pg; MCHC 28 g/dL; Serum ferritin 6 ng/mL (low); TIBC elevated. What is the diagnosis and likely cause?"

Strategy: (i) Hb 8.2 = anaemia (WHO threshold <12 g/dL women/<13 g/dL men); (ii) MCV 70 = microcytic (<80 fL); (iii) MCH 21 + MCHC 28 = hypochromic; (iv) low ferritin = iron stores depleted; (v) high TIBC = body seeking more iron. Diagnosis: iron-deficiency anaemia (microcytic, hypochromic). Most common cause: chronic blood loss (GI bleed, menorrhagia) or dietary deficiency. Management: oral iron supplementation (ferrous sulphate), identify and treat underlying cause.

10.8 Quick-Reference Tables

10.8.1 Common Tests for Infectious Diseases at a Glance

**Table 10.6**Infectious diseases: key diagnostic test summary
Disease	Pathogen	Screening / Rapid	Confirmatory / Gold Std	Marker / Antigen
HIV/AIDS	HIV-1/2 retrovirus	4th-gen ELISA (Ab+Ag)	Western blot / HIV RNA PCR	p24 Ag; CD4 count, viral load
Tuberculosis	M. tuberculosis	ZN stain (AFB); Mantoux; IGRA	LJ culture (4–8 wks)	GeneXpert MTB/RIF (2 h)
Malaria	Plasmodium spp.	RDT (HRP-2/pLDH); <15 min	Peripheral blood smear (Giemsa)	HRP-2 = P. falciparum specific
Dengue	Dengue virus (DENV)	NS1 antigen (days 1–5)	RT-PCR; IgM ELISA	NS1; IgM (day 5+), IgG (past)
Typhoid	S. typhi	Widal test; Typhi-dot IgM	Blood culture (wk 1)	O + H agglutinins
Hepatitis B	HBV (DNA virus)	HBsAg ELISA	HBV DNA PCR (viral load)	HBsAg; HBeAg; anti-HBc IgM
Hepatitis C	HCV (RNA virus)	Anti-HCV ELISA	HCV RNA PCR (viral load)	Anti-HCV; core antigen
COVID-19	SARS-CoV-2	RAT (rapid antigen test)	RT-PCR (nasopharyngeal)	Nucleocapsid / Spike protein Ag
Brucellosis	Brucella spp.	SAT agglutination (≥1:160)	Blood/bone marrow culture (BACTEC)	Rose Bengal Test (RBT) for screening

Chapter 10 — Recap

Blood = plasma (55%) + formed elements (45%; RBC, WBC, platelets). Plasma proteins: albumin (oncotic pressure), globulins (immunoglobulins), fibrinogen (clotting).
CBC normal ranges: RBC 4.0–5.5 M/µL; Hb 12–17.5 g/dL; WBC 4,000–11,000/µL; platelets 1.5–4.5 lakh/µL; MCV 80–100 fL.
Anaemia classification: microcytic hypochromic (iron def, thalassaemia); macrocytic megaloblastic (B₁₂/folate def); aplastic (pancytopenia); haemolytic (high retics, low haptoglobin).
Sickle-cell: β-globin Glu→Val mutation; autosomal recessive; malaria resistance in heterozygotes. Thalassaemia: reduced α or β globin synthesis.
ABO blood groups: Landsteiner 1900; Universal donor O−; Universal recipient AB+. Rh incompatibility in pregnancy → erythroblastosis foetalis; prevent with anti-D Ig.
Coagulation: intrinsic (XII) + extrinsic (TF:VII) → common (X) → prothrombin → thrombin → fibrin. Vitamin K-dependent: II, VII, IX, X. PT/INR = extrinsic; aPTT = intrinsic; heparin monitored by aPTT; warfarin by INR.
Diabetes criteria: FPG ≥126 mg/dL (×2); OGTT 2-h ≥200; HbA1c ≥6.5%. HbA1c = 3-month average glucose. T1 = autoimmune; T2 = insulin resistance. HDL protective; LDL atherogenic.
Imaging: X-ray (Roentgen 1895) — bone/chest; USG — no radiation, abdomen/pregnancy; CT (Hounsfield Nobel 1979) — multiple X-rays, more radiation; MRI (Lauterbur-Mansfield Nobel 2003) — no radiation, best soft tissue; PET-FDG — metabolic/cancer staging.
Bacterial diagnostics: Gram stain, culture (gold std), PCR, ELISA/serology. Acid-fast: ZN stain; TB gold std = LJ culture; GeneXpert MTB/RIF rapid PCR. Sensitivity: disk diffusion (Kirby-Bauer) or MIC.
Viral diagnostics: ELISA (Engvall-Perlmann 1971); RT-PCR (RNA viruses); IgM = acute; IgG = past/immune. HIV: 4th-gen ELISA, confirm Western blot/PCR. Malaria: thick smear + RDT.
Cancer: benign = encapsulated, no metastasis; malignant = invasive, metastasises. Carcinoma (epithelial, >85%), sarcoma (mesenchymal), leukaemia (blood), lymphoma (lymphoid). TNM staging.
Tumour markers: PSA (prostate), CEA (colorectal), AFP (HCC, testicular), CA-125 (ovarian), CA 19-9 (pancreatic), βhCG (gestational trophoblastic).
HP angle: High-altitude polycythemia (Lahaul-Spiti); IGMC Shimla cancer registry; historic iodine deficiency goitre (mostly resolved by NIDDCP); Hep B endemic patches; brucellosis in livestock workers.

Chapter 10 Cheatsheet

Blood Composition

Plasma 55%: water 91%, proteins 7% (albumin > globulins > fibrinogen), dissolved solutes 2%
Cells 45%: RBC (biconcave, no nucleus), WBC (5 types), platelets (anucleate)
Serum = plasma − clotting factors

CBC Key Values

Hb: men 13.5–17.5; women 12.0–15.5 g/dL
MCV 80–100 fL; microcytic <80; macrocytic >100
WBC 4,000–11,000/µL; platelets 1.5–4.5 L/µL
Reticulocytes 0.5–2.5%

Anaemia Quick Ref

Microcytic: Fe def, thalassaemia, sideroblastic
Macrocytic: B₁₂ def, folate def, liver disease
Aplastic: pancytopenia (all lines low)
Sickle cell: Glu→Val (A→T) in β-globin
Haemolytic: high retics, low haptoglobin

Blood Groups

Landsteiner 1900 (Nobel 1930)
O− = universal donor; AB+ = universal recipient
Rh− mother + Rh+ foetus → erythroblastosis foetalis
Prevent: anti-D Ig (Rhogam) at 28 wks + 72 h post-delivery

Coagulation

Intrinsic: XII → XI → IX + VIII (aPTT)
Extrinsic: TF + VII (PT/INR)
Common: X → thrombin → fibrin
Vit K factors: II, VII, IX, X
Warfarin monitored by INR; heparin by aPTT
Haemophilia A = VIII def; B = IX def (both X-linked)

Diabetes Tests

Diabetes: FPG ≥126; OGTT ≥200; HbA1c ≥6.5%
HbA1c = 3-month Hb glycation; 1% ≈ 30 mg/dL
T1: autoimmune, insulin-dep; T2: insulin resistance
LDL <100 mg/dL target; HDL >40 (M), >50 (F)

Imaging Modalities

X-ray (Roentgen 1895) — bone, chest; ionising
USG — no radiation; abdomen, obstetric, echo
CT (Hounsfield Nobel 1979) — fast; higher radiation
MRI (Lauterbur-Mansfield Nobel 2003) — no radiation; T1/T2
PET-FDG — metabolic; cancer staging; F-18

Key Diagnostic Methods

ELISA: Engvall & Perlmann 1971 — Ab/Ag detection
PCR: Mullis 1983, Nobel 1993 — DNA amplification
Gram stain: Gram 1884 — Gram+ve purple; −ve pink
ZN stain: acid-fast (TB, leprosy) — red on blue
Western blot: protein electrophoresis + Ab detection
GeneXpert MTB/RIF: rapid TB PCR, 2 h

Tumour Markers

PSA — prostate; CEA — colorectal
AFP — HCC + testicular germ cell
CA-125 — ovarian; CA 19-9 — pancreatic
βhCG — gestational trophoblastic
Carcinoma >85% cancers (epithelial)
Reed-Sternberg cells: Hodgkin's lymphoma
Philadelphia chr (BCR-ABL): CML — imatinib

HP-Specific Items

High-altitude polycythemia: Lahaul-Spiti (>4,000 m)
IGMC Shimla: HP Cancer Registry (PBCR/NCRP)
Iodine deficiency goitre: historically in Shimla, Mandi, Solan; NIDDCP salt iodisation largely resolved
Brucellosis: livestock workers, Kullu/Kangra/Chamba
Hep B endemic patches in certain HP tribal areas

Cross-references

Ch. 7 — Human Physiology: blood circulation, cardiac cycle, ECG physiology.
Ch. 8 — Immunology: antibody structure, ELISA principle, vaccine types, complement.
Ch. 9 — Endocrinology: insulin-glucagon axis, thyroid hormones, adrenal cortex (cortisol for immune suppression), reproductive hormones (βhCG in pregnancy).
Ch. 11 — Genetics: karyotyping, FISH, PCR applications, NGS; haemophilia inheritance; sickle cell genetics.
Ch. 1 — Plant Diversity: Gram staining principles share conceptual roots with bacterial taxonomy; antibiotic origins (Streptomyces).

Practice Questions

Which blood group is the universal donor? HPRCA-pat.

AB+
AB−
O+
O−

Answer: D — O−

O blood group has no A or B antigens (so anti-A and anti-B antibodies in recipient's plasma won't react); Rh− has no D antigen. O− is therefore safe to transfuse to any patient in emergency. AB+ is the universal recipient.

Normal range of HbA1c for diagnosing diabetes mellitus is: HPRCA-pat.

≥5.7%
≥6.0%
≥6.5%
≥7.0%

Answer: C — ≥6.5%

ADA (2024) diagnostic threshold for diabetes: HbA1c ≥6.5% on two occasions (or once with symptoms). Normal <5.7%; pre-diabetes 5.7–6.4%. It reflects average plasma glucose over the preceding 3 months (RBC lifespan ~120 days).

The ELISA technique was developed by: HPRCA-pat.

Mullis and Smith (1983)
Engvall and Perlmann (1971)
Lauterbur and Mansfield (2003)
Landsteiner and Wiener (1940)

Answer: B — Engvall and Perlmann (1971)

ELISA (Enzyme-Linked Immunosorbent Assay) was developed by Eva Engvall and Peter Perlmann in 1971. PCR was developed by Kary Mullis 1983 (Nobel 1993). MRI Nobel 2003: Lauterbur and Mansfield. ABO blood groups: Landsteiner 1900.

In the coagulation cascade, Prothrombin Time (PT/INR) specifically tests which pathway? HPRCA-pat.

Intrinsic pathway only
Extrinsic + common pathway
Common pathway only
Intrinsic + common pathway

Answer: B — Extrinsic + common pathway

PT/INR tests Factors I, II, V, VII, X (extrinsic + common). aPTT tests the intrinsic + common pathway (Factors I, II, V, VIII, IX, X, XI, XII). Heparin therapy is monitored by aPTT; warfarin by INR.

Which imaging modality uses radiofrequency pulses in a strong magnetic field and produces no ionising radiation? HPRCA-pat.

CT scan
X-ray
MRI
PET scan

Answer: C — MRI

MRI uses magnetic field + RF pulses; no ionising radiation. Nobel 2003: Lauterbur and Mansfield. PET uses radiotracer (F-18 FDG) which emits positrons — ionising. CT and X-ray both use ionising radiation.

The sickle-cell mutation changes the amino acid at position 6 of β-globin from:

Valine to Glutamic acid
Glutamic acid to Valine
Glutamine to Lysine
Lysine to Glutamic acid

Answer: B — Glutamic acid to Valine

The point mutation is A→T in the DNA codon for position 6 of β-globin, converting GAG (Glu) to GTG (Val). This single amino acid change causes HbS to polymerise under low oxygen tension, distorting RBCs into a sickle shape.

GeneXpert MTB/RIF is specifically used for: HPRCA-pat.

Detecting dengue NS1 antigen
Rapid diagnosis of TB and rifampicin resistance
HIV viral load quantification
Blood group typing in emergency transfusion

Answer: B — Rapid diagnosis of TB and rifampicin resistance

GeneXpert MTB/RIF is a nested real-time PCR that detects M. tuberculosis DNA and mutations in the rpoB gene conferring rifampicin resistance — result in <2 hours. WHO-endorsed as the initial diagnostic test for TB in high-burden countries.

Which tumour marker is most specific for ovarian carcinoma monitoring?

CEA
AFP
CA-125
PSA

Answer: C — CA-125

CA-125 (Cancer Antigen 125 / MUC16) is used for monitoring ovarian cancer treatment response and detecting recurrence. PSA is for prostate cancer; CEA for colorectal; AFP for HCC and testicular germ-cell tumours. Note: CA-125 is not specific enough for screening in the general population.

Reed-Sternberg cells are pathognomonic of: HPRCA-pat.

Chronic myeloid leukaemia
Non-Hodgkin’s lymphoma
Hodgkin’s lymphoma
Acute lymphoblastic leukaemia

Answer: C — Hodgkin’s lymphoma

Reed-Sternberg (RS) cells are the hallmark of Hodgkin’s lymphoma — large binucleated cells with prominent "owl-eye" nucleoli on H&E staining. CML has the Philadelphia chromosome (BCR-ABL). NHL is diagnosed by B- or T-cell markers without RS cells.

Peripheral blood smear showing the malaria parasite (Plasmodium falciparum) ring-form trophozoites can be stained with which stain? HPRCA-pat.

Gram stain
Ziehl-Neelsen stain
Giemsa stain
PAS stain

Answer: C — Giemsa stain

Giemsa stain (also Wright or Leishman) is used for blood smear examination for malaria, trypanosomes, and to differentiate WBC types. Ziehl-Neelsen is for acid-fast bacilli (TB, leprosy). Gram stain is for bacteria.

The metabolic syndrome criterion that specifically relates to blood lipids is:

FPG ≥100 mg/dL + HDL <40 mg/dL (men)
Waist circumference >102 cm (men)
Blood pressure ≥130/85 mmHg
BMI ≥30 kg/m²

Answer: A — FPG ≥100 mg/dL + HDL <40 mg/dL (men)

Metabolic syndrome requires any 3 of 5 criteria: (1) central obesity (waist >102/88 cm M/F), (2) TG ≥150 mg/dL, (3) low HDL (<40 M; <50 F), (4) BP ≥130/85, (5) FPG ≥100 mg/dL. The lipid-specific criteria are elevated TG and low HDL.

Assertion (A): Vitamin K deficiency prolongs the Prothrombin Time (PT/INR) but does not affect the platelet count.
Reason (R): Vitamin K is required for the carboxylation and activation of coagulation Factors II, VII, IX, and X. HPRCA-pat.

Both A and R are true and R is the correct explanation of A
Both A and R are true but R is not the correct explanation of A
A is true but R is false
A is false but R is true

Answer: A — Both A and R are true; R correctly explains A

Vitamin K enables γ-carboxylation of glutamate residues on Factors II (prothrombin), VII, IX, and X, making them functionally active. Deficiency reduces these factors → prolonged PT (extrinsic + common pathway). Platelet production is independent of vitamin K.

Assertion (A): MRI is contraindicated in patients with ferromagnetic cardiac pacemakers.
Reason (R): MRI uses strong magnetic fields that could displace or interfere with ferromagnetic metallic implants.

Both A and R are true and R is the correct explanation of A
Both A and R are true but R is not the correct explanation of A
A is true but R is false
A is false but R is true

Answer: A — Both A and R are true; R correctly explains A

The powerful magnetic field in MRI (≥1.5 Tesla clinical; 3T research) can heat, torque, or displace ferromagnetic implants, cause pacemaker malfunction, and interfere with electrical circuitry. MRI-conditional pacemakers exist but must be individually verified.

Assertion (A): In sickle-cell anaemia, heterozygous carriers (HbAS) are relatively protected against Plasmodium falciparum malaria.
Reason (R): The sickled RBC environment is inhospitable for malaria parasite growth, conferring a survival advantage in malaria-endemic areas. HPRCA-pat.

Both A and R are true and R is the correct explanation of A
Both A and R are true but R is not the correct explanation of A
A is true but R is false
A is false but R is true

Answer: A — Both A and R are true; R correctly explains A

This is a classic example of heterozygous advantage (balancing selection). HbAS cells sickle under low O₂ conditions inside P. falciparum-infected erythrocytes, impairing parasite growth and clearance. This explains the high frequency of the HbS allele in sub-Saharan Africa and tribal India where malaria is endemic.

Assertion (A): PET scan uses radioactive glucose analogue (¹⁸F-FDG) as a tracer and is preferred for cancer staging over MRI in most solid tumours.
Reason (R): Cancer cells have elevated glucose metabolism (Warburg effect) and take up more FDG than normal cells, producing high signal on PET.

Both A and R are true and R is the correct explanation of A
Both A and R are true but R is not the correct explanation of A
A is true but R is false
A is false but R is true

Answer: A — Both A and R are true; R correctly explains A

The Warburg effect (aerobic glycolysis in tumour cells; Warburg 1924) underlies FDG-PET imaging. Tumour cells overexpress GLUT transporters and glucose metabolism, accumulating FDG (which is not further metabolised, so it is trapped in the cell). PET-CT is now standard for cancer staging, treatment response, and surveillance in many cancers.

Match the tumour marker with the cancer it primarily monitors: HPRCA-pat.

Column I (Marker)	Column II (Cancer)
(a) PSA	(i) Ovarian carcinoma
(b) AFP	(ii) Prostate cancer
(c) CA-125	(iii) Hepatocellular carcinoma / Testicular
(d) CA 19-9	(iv) Pancreatic cancer

a-ii, b-iii, c-i, d-iv
a-i, b-ii, c-iii, d-iv
a-ii, b-i, c-iv, d-iii
a-iii, b-iv, c-ii, d-i

Answer: A — a-ii, b-iii, c-i, d-iv

PSA = prostate; AFP = hepatocellular carcinoma & testicular germ-cell tumours; CA-125 = ovarian carcinoma monitoring; CA 19-9 = pancreatic cancer (and cholangiocarcinoma).

Match the imaging modality with its primary physical principle: HPRCA-pat.

Column I (Modality)	Column II (Principle)
(a) X-ray	(i) Radiotracer positron emission
(b) MRI	(ii) High-frequency sound wave reflection
(c) PET	(iii) Magnetic field + RF pulse (proton relaxation)
(d) Ultrasound	(iv) Ionising electromagnetic radiation attenuation

a-iv, b-iii, c-i, d-ii
a-iii, b-iv, c-ii, d-i
a-i, b-ii, c-iii, d-iv
a-iv, b-i, c-iii, d-ii

Answer: A — a-iv, b-iii, c-i, d-ii

X-ray: ionising radiation differential attenuation. MRI: nuclear magnetic resonance of protons (H nuclei). PET: radiotracer emits positrons, detected as annihilation gamma pairs. USG: sound wave reflection (no radiation).

Match the discoverer/Nobel year with the achievement:

Column I	Column II
(a) Roentgen, 1895	(i) MRI Nobel Prize 2003
(b) Landsteiner, 1900	(ii) Discovery of X-rays (Nobel 1901)
(c) Lauterbur & Mansfield	(iii) PCR technique (Nobel 1993)
(d) Mullis, 1983	(iv) ABO blood group system (Nobel 1930)

a-ii, b-iv, c-i, d-iii
a-i, b-ii, c-iii, d-iv
a-iv, b-iii, c-ii, d-i
a-ii, b-i, c-iv, d-iii

Answer: A — a-ii, b-iv, c-i, d-iii

Roentgen 1895 → X-rays (Nobel 1901); Landsteiner 1900 → ABO (Nobel 1930); Lauterbur & Mansfield → MRI (Nobel 2003); Mullis 1983 → PCR (Nobel 1993).

Consider the following statements about anaemia: HPRCA-pat.

Iron-deficiency anaemia is the most common nutritional anaemia worldwide and typically shows microcytic hypochromic red cells.
Vitamin B₁₂ deficiency anaemia shows neurological features because myelin synthesis requires adenosylcobalamin.
Aplastic anaemia results specifically from destruction of erythroid precursors only, leaving WBC and platelet counts normal.
Sickle-cell anaemia heterozygotes (HbAS) show clinical symptoms similar to homozygotes under normal conditions.

Which of the above statements are correct?

I and II only
I, II and III only
II, III and IV only
I, II and IV only

Answer: A — I and II only

Statement I: correct. Statement II: correct — B₁₂ (cobalamin) is essential for myelin synthesis via methylmalonyl-CoA pathway; its deficiency causes subacute combined degeneration of the spinal cord. Statement III: incorrect — aplastic anaemia causes pancytopenia (all three cell lines reduced) due to haematopoietic stem cell failure, not just RBCs. Statement IV: incorrect — HbAS (sickle-cell trait) carriers are largely asymptomatic under normal conditions; symptoms only occur under extreme hypoxia.

Consider the following statements about cancer diagnostics:

FNAC provides a histological (architectural) diagnosis of tumour tissue.
Liquid biopsy detects circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) in peripheral blood.
IHC with CK (cytokeratin) markers helps distinguish carcinomas from sarcomas.

Which statements are correct?

I and II only
II and III only
I and III only
I, II and III

Answer: B — II and III only

Statement I: incorrect — FNAC (fine-needle aspiration cytology) provides cytological diagnosis (individual cells), not architectural/histological diagnosis. Histology requires biopsy (core needle or excisional) with tissue sections. Statements II and III are correct.

Arrange the following discoveries in correct chronological order: HPRCA-pat.

Discovery of X-rays (Roentgen)
ABO blood group system (Landsteiner)
ELISA technique (Engvall & Perlmann)
PCR technique (Mullis)

I → II → III → IV
II → I → IV → III
I → III → II → IV
II → III → I → IV

Answer: A — I → II → III → IV

Roentgen 1895 (X-rays) → Landsteiner 1900 (ABO) → Engvall & Perlmann 1971 (ELISA) → Mullis 1983 (PCR). Banting & Best 1922 (insulin) and Lauterbur-Mansfield 2003 (MRI Nobel) are also key chronology items.

Which of the following is the odd one out with respect to cancer type classification? HPRCA-pat.

Osteosarcoma
Liposarcoma
Leiomyosarcoma
Adenocarcinoma

Answer: D — Adenocarcinoma

Osteosarcoma (bone), liposarcoma (fat), and leiomyosarcoma (smooth muscle) are all sarcomas — malignancies of mesenchymal/connective tissue. Adenocarcinoma is a carcinoma — malignancy of glandular epithelium. This is the odd one out by tissue origin.

End of Chapter 10 · Medical Diagnostics. HPRCA-pat. indicates HPRCA / state-TGT pattern questions; literal past-paper items will be flagged with year when official papers are sourced.

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