Pathology
MBBS Pathology — high-yield long questions and short notes from Robbins & Cotran and Harsh Mohan, covering general pathology (cell injury, inflammation, haemodynamics, immunopathology, neoplasia), haematology, and systemic pathology of the cardiovascular, respiratory, GI, hepatobiliary, renal, endocrine and other systems, written to the marks with definitions, mechanisms, morphology, classification, clinical correlation and pearls.
12chapters144questions99High-Yield
Definition
Hypersensitivity is an exaggerated or inappropriate immune response causing tissue injury, classified by Gell and Coombs into four types.
Types I–III (antibody-mediated)
- Type I (immediate, IgE) — mast cell degranulation: anaphylaxis, asthma, urticaria, hay fever
- Type II (cytotoxic, IgG/IgM) — antibody against cell-surface antigen: haemolytic disease of newborn, transfusion reaction, Goodpasture, myasthenia gravis
- Type III (immune complex) — complex deposition + complement: SLE, post-streptococcal glomerulonephritis, serum sickness, Arthus reaction
Type IV (cell-mediated)
- T-cell mediated, delayed 24–72 hours
- CD4 cells → cytokines → macrophage activation; CD8 → direct cytotoxicity
- Examples: tuberculin (Mantoux) test, contact dermatitis, granuloma formation, graft rejection
Prior sensitisation turns a protective response into a damaging one. Type Mediator Example I IgE Anaphylaxis II IgG/IgM Haemolysis III Immune complex SLE IV T cell Mantoux test Applied
- Anaphylaxis → intramuscular adrenaline immediately
- Type IV underlies the tuberculin test and transplant rejection
🔑KEY POINTS TO REMEMBER- Four types: I IgE, II cytotoxic, III immune complex, IV delayed T-cell.
- Types I–III antibody-mediated; Type IV cell-mediated (24–72 h).
- Type I = anaphylaxis; Type IV = tuberculin reaction and contact dermatitis.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Autoimmunity is immune-mediated injury caused by loss of self-tolerance; SLE is the prototype multisystem autoimmune disease.
Mechanisms of Autoimmunity
- Failure of self-tolerance (central and peripheral)
- Molecular mimicry — microbial antigens resembling self
- Release of sequestered antigens (lens, sperm, myelin)
- Polyclonal lymphocyte activation; genetic (HLA) susceptibility
- Female preponderance (hormonal influence)
Systemic Lupus Erythematosus
- Type III (immune complex) with some Type II features
- Antinuclear antibody (ANA) — sensitive screening test
- Anti-dsDNA and anti-Smith — highly specific
- Features: malar (butterfly) rash, photosensitivity, arthritis, serositis, lupus nephritis, cytopenias, neuropsychiatric disease
- Libman-Sacks endocarditis; wire-loop lesions in kidney
Circulating complexes deposit widely, explaining the multisystem disease. Antibody Significance ANA Sensitive, screening Anti-dsDNA Specific, nephritis Anti-Sm Highly specific Applied
- Lupus nephritis largely determines prognosis
- Treatment: steroids, hydroxychloroquine, immunosuppressants
🔑KEY POINTS TO REMEMBER- Autoimmunity results from loss of self-tolerance, molecular mimicry, sequestered antigens.
- SLE is a Type III immune-complex multisystem disease.
- ANA is sensitive; anti-dsDNA and anti-Sm are specific.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Immunodeficiency disorders are conditions with defective immune function, predisposing to recurrent and opportunistic infections.
Primary (congenital)
- B-cell defects — Bruton X-linked agammaglobulinaemia, IgA deficiency (commonest); recurrent pyogenic infections
- T-cell defects — DiGeorge syndrome (thymic aplasia); viral/fungal infections
- Combined — SCID, Wiskott-Aldrich, ataxia telangiectasia
- Phagocyte — chronic granulomatous disease, Chediak-Higashi
- Complement — C3 (pyogenic), C5–9 (neisserial), C1 inhibitor (angioedema)
Secondary (acquired) — commoner
- HIV/AIDS, malnutrition, malignancy (leukaemia, lymphoma)
- Drugs — corticosteroids, chemotherapy, immunosuppressants
- Diabetes, chronic kidney disease, splenectomy, ageing, irradiation
The arm of immunity affected predicts the type of infection. Defect Infection type B cell Pyogenic bacteria T cell Viral, fungal Phagocyte Catalase-positive bacteria Applied
- Suspect primary immunodeficiency with recurrent infections from infancy
- Live vaccines are contraindicated in T-cell defects
🔑KEY POINTS TO REMEMBER- Primary immunodeficiency: B-cell, T-cell, combined, phagocyte, complement defects.
- Secondary is commoner — HIV, malnutrition, drugs, malignancy.
- B-cell defects → pyogenic; T-cell defects → viral and fungal infections.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
HIV infection is a retroviral disease that progressively destroys CD4 T lymphocytes, culminating in AIDS.
Virus & Pathogenesis
- Enveloped RNA retrovirus with reverse transcriptase; HIV-1 and HIV-2
- gp120 binds CD4 plus CCR5/CXCR4 coreceptors
- Integrates as provirus → latent reservoir
- Progressive CD4 depletion → loss of cell-mediated immunity
- Transmission: sexual, blood, vertical
Clinical Course
- Acute seroconversion illness → clinical latency → symptomatic → AIDS
- AIDS: CD4 <200/μL or an AIDS-defining illness
- Opportunistic infections: tuberculosis, Pneumocystis, candidiasis, cryptococcal meningitis, CMV retinitis, toxoplasmosis
- Malignancies: Kaposi sarcoma (HHV-8), lymphoma, cervical cancer
Falling CD4 counts determine which complications appear. CD4 count Risk <200/μL Pneumocystis <100/μL Cryptococcus, toxoplasma <50/μL CMV, MAC Applied
- Diagnosis: ELISA screening, confirmation; p24 antigen/PCR in window period
- Lifelong antiretroviral therapy; PMTCT prevents vertical transmission
🔑KEY POINTS TO REMEMBER- HIV targets CD4 cells via gp120 and reverse transcriptase.
- AIDS = CD4 <200/μL or an AIDS-defining illness.
- CD4 count predicts specific opportunistic infections.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Amyloidosis is extracellular deposition of abnormal β-pleated sheet fibrillar protein causing progressive organ dysfunction.
Properties & Staining
- All amyloid has a β-pleated sheet structure
- Congo red stain → apple-green birefringence under polarised light
- Homogeneous pink on H&E; metachromasia with methyl violet
- Contains serum amyloid P component and glycosaminoglycans
Classification
- AL (primary) — immunoglobulin light chains; multiple myeloma, plasma cell dyscrasia
- AA (secondary) — serum amyloid A; chronic inflammation (tuberculosis, rheumatoid arthritis, bronchiectasis, osteomyelitis)
- Aβ2M — long-term dialysis; ATTR — familial/senile cardiac
- Aβ — Alzheimer disease; AE — medullary thyroid carcinoma
Misfolded protein accumulates faster than it can be cleared. Type Protein Setting AL Light chain Myeloma AA Serum amyloid A Chronic inflammation Aβ β-amyloid Alzheimer Applied
- Kidney involvement → nephrotic syndrome (commonest cause of death)
- Diagnosis: abdominal fat pad or rectal biopsy with Congo red
🔑KEY POINTS TO REMEMBER- Amyloid is extracellular β-pleated sheet protein.
- Congo red gives apple-green birefringence — diagnostic.
- AL from light chains (myeloma); AA from chronic inflammation.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Type I hypersensitivity is an IgE-mediated immediate allergic reaction occurring within minutes of re-exposure to antigen.
Mechanism
- Sensitisation — first exposure → Th2 response → IgE binds mast cells and basophils
- Re-exposure → antigen cross-links IgE → degranulation
- Primary mediators — histamine, tryptase (immediate, minutes)
- Secondary mediators — leukotrienes, prostaglandins, cytokines (late phase, 4–24 h)
Clinical Forms
- Systemic — anaphylaxis: bronchospasm, laryngeal oedema, hypotension, shock
- Local (atopy) — allergic rhinitis, bronchial asthma, urticaria, food and drug allergy
- Eosinophilia and raised serum IgE
- Diagnosis: skin prick test, specific IgE (RAST)
Preformed mediators explain why the reaction is almost instantaneous. Phase Time Mediator Immediate Minutes Histamine Late 4–24 h Leukotrienes Applied
- Anaphylaxis → intramuscular adrenaline first
- Antihistamines and steroids are adjuncts, not first-line in anaphylaxis
🔑KEY POINTS TO REMEMBER- Type I is IgE-mediated with mast cell degranulation.
- Histamine causes the immediate phase; leukotrienes the late phase.
- Anaphylaxis is treated with intramuscular adrenaline.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Type IV hypersensitivity is a T-cell mediated reaction developing over 24–72 hours, with no antibody involvement.
Mechanism
- CD4 Th1 cells recognise antigen → release IFN-γ
- Macrophages activated → epithelioid cells and granuloma
- CD8 cytotoxic cells directly kill target cells
- No antibody, no complement; peak at 48–72 hours
Examples
- Tuberculin (Mantoux) test — classic
- Contact dermatitis — nickel, chemicals, cosmetics
- Granulomatous — tuberculosis, leprosy, sarcoidosis, schistosomiasis
- Transplant rejection (acute cellular), type 1 diabetes, multiple sclerosis
Cellular recruitment takes days, hence the delayed response. Feature Type I Type IV Mediator IgE T cell Onset Minutes 24–72 h Transfer Serum Cells Applied
- Can be transferred by cells, not serum
- Basis of the Mantoux and patch tests
🔑KEY POINTS TO REMEMBER- Type IV is T-cell mediated, peaking at 48–72 hours.
- CD4 cells release IFN-γ forming granulomas; CD8 cells kill directly.
- Examples: Mantoux test, contact dermatitis, tuberculosis, graft rejection.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease caused by immune complex deposition.
Clinical Features
- Young women predominantly (female:male about 9:1)
- Malar butterfly rash, photosensitivity, discoid rash, oral ulcers, alopecia
- Non-erosive arthritis, serositis (pleurisy, pericarditis)
- Lupus nephritis — determines prognosis; wire-loop lesions
- Haematological — anaemia, leucopenia, thrombocytopenia; neuropsychiatric features
- Libman-Sacks endocarditis (non-bacterial vegetations)
Investigations
- ANA — most sensitive (screening)
- Anti-dsDNA — specific, correlates with nephritis activity
- Anti-Smith — most specific
- Low complement (C3, C4) during flares; LE cell phenomenon
- Antiphospholipid antibodies → thrombosis, recurrent abortion
Widespread complex deposition explains the multisystem presentation. Antibody Value ANA Sensitive Anti-dsDNA Nephritis activity Anti-Sm Most specific Applied
- Renal biopsy classifies lupus nephritis and guides therapy
- Treatment: hydroxychloroquine, steroids, immunosuppressants
🔑KEY POINTS TO REMEMBER- SLE is a Type III immune-complex disease of young women.
- Butterfly rash, arthritis, serositis and lupus nephritis are typical.
- ANA is sensitive; anti-dsDNA and anti-Sm are specific.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Graft rejection is immune-mediated destruction of transplanted tissue recognised as foreign, chiefly through HLA differences.
Types by Timing
- Hyperacute — minutes to hours; preformed antibodies (Type II); thrombosis and infarction of graft
- Acute — days to months; mainly T-cell mediated (cellular) ± humoral; reversible with immunosuppression
- Chronic — months to years; intimal fibrosis, vascular narrowing, progressive graft failure
Terminology & Prevention
- Autograft (self), isograft (identical twin), allograft (same species), xenograft (different species)
- Graft-versus-host disease — donor cells attack host (bone marrow transplant): rash, diarrhoea, jaundice
- Prevention: HLA matching, ABO compatibility, crossmatching
- Immunosuppression: ciclosporin/tacrolimus, steroids, mycophenolate
Timing of rejection reveals which immune mechanism is responsible. Type Timing Mechanism Hyperacute Minutes Preformed antibody Acute Days–months T cell Chronic Months–years Fibrosis Applied
- Crossmatching prevents hyperacute rejection
- Immunosuppression increases infection and malignancy risk
🔑KEY POINTS TO REMEMBER- Hyperacute rejection: minutes, preformed antibodies.
- Acute: days to months, T-cell mediated, reversible.
- Chronic: months to years with intimal fibrosis; GVHD occurs in marrow transplants.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Opportunistic infections are infections by organisms of low virulence that occur because of severe immunodeficiency, and define AIDS.
By CD4 Count
- Any count — tuberculosis (commonest in India), bacterial pneumonia, herpes zoster
- <200/μL — Pneumocystis jirovecii pneumonia, oesophageal candidiasis
- <100/μL — cryptococcal meningitis, cerebral toxoplasmosis, cryptosporidiosis
- <50/μL — CMV retinitis, Mycobacterium avium complex
Malignancies & Prophylaxis
- Kaposi sarcoma (HHV-8), non-Hodgkin lymphoma, cervical carcinoma
- Co-trimoxazole prophylaxis when CD4 <200/μL (Pneumocystis, toxoplasma)
- Isoniazid preventive therapy for tuberculosis
- Antiretroviral therapy restores CD4 and prevents recurrence
Each threshold of CD4 decline unlocks a new set of infections. CD4 Infection <200 Pneumocystis <100 Cryptococcus, toxoplasma <50 CMV, MAC Applied
- Tuberculosis is the commonest opportunistic infection in India
- Immune reconstitution syndrome may follow starting therapy
🔑KEY POINTS TO REMEMBER- Opportunistic infections define AIDS and follow CD4 thresholds.
- CD4 <200 → Pneumocystis; <100 → cryptococcus/toxoplasma; <50 → CMV.
- Co-trimoxazole prophylaxis and antiretroviral therapy prevent them.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Primary immunodeficiencies are inherited defects of the immune system, usually presenting in infancy or childhood with recurrent infections.
B-Cell and T-Cell Defects
- Bruton X-linked agammaglobulinaemia — BTK gene; no B cells; recurrent pyogenic infections after 6 months (when maternal IgG wanes)
- Selective IgA deficiency — commonest primary immunodeficiency; mucosal infections, anaphylaxis to blood products
- DiGeorge syndrome — 22q11 deletion; thymic and parathyroid aplasia; tetany, cardiac defects, viral/fungal infections
Combined and Phagocyte Defects
- SCID — both B and T cell defect; fatal without bone marrow transplant
- Wiskott-Aldrich — eczema, thrombocytopenia, recurrent infection (X-linked)
- Chronic granulomatous disease — NADPH oxidase defect; catalase-positive organisms; abnormal NBT test
- Chediak-Higashi — giant granules, partial albinism
- Complement: C5–9 deficiency → recurrent neisserial infection
The infecting organism points to which immune component is missing. Disorder Defect Bruton B cells absent DiGeorge Thymic aplasia CGD NADPH oxidase Applied
- Recurrent infections from infancy warrant immune workup
- Live vaccines contraindicated in T-cell and combined defects
🔑KEY POINTS TO REMEMBER- IgA deficiency is the commonest; Bruton is X-linked with absent B cells.
- DiGeorge = thymic aplasia with tetany; SCID needs marrow transplant.
- Chronic granulomatous disease: NADPH oxidase defect, abnormal NBT test.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Autoantibodies are antibodies directed against self-antigens; their pattern helps diagnose and classify autoimmune diseases.
Systemic Diseases
- ANA — SLE (sensitive screen), also other connective tissue diseases
- Anti-dsDNA, anti-Sm — specific for SLE
- Anti-histone — drug-induced lupus
- Rheumatoid factor, anti-CCP — rheumatoid arthritis (anti-CCP more specific)
- Anti-centromere — CREST; anti-Scl-70 — diffuse systemic sclerosis
- Anti-Ro/La — Sjögren syndrome; ANCA — vasculitis
Organ-Specific Diseases
- Anti-TPO, anti-thyroglobulin — Hashimoto thyroiditis; TSH receptor antibody — Graves disease
- Anti-acetylcholine receptor — myasthenia gravis
- Anti-GBM — Goodpasture syndrome
- Anti-mitochondrial — primary biliary cholangitis
- Anti-tissue transglutaminase — coeliac disease; anti-intrinsic factor — pernicious anaemia
The target antigen determines whether disease is localised or systemic. Antibody Disease Anti-dsDNA SLE Anti-CCP Rheumatoid arthritis Anti-AChR Myasthenia gravis Applied
- ANA is a screening test; specific antibodies confirm the diagnosis
- Low titres may occur in healthy elderly people
🔑KEY POINTS TO REMEMBER- Anti-dsDNA/anti-Sm are specific for SLE; anti-histone for drug-induced lupus.
- Anti-CCP is specific for rheumatoid arthritis.
- Organ-specific: anti-TPO (Hashimoto), anti-AChR (myasthenia), anti-GBM (Goodpasture).
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.