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
Acute inflammation is the immediate, short-lived vascular and cellular response of living tissue to injury, aimed at eliminating the cause.
Vascular Changes
- Transient vasoconstriction, then vasodilatation → redness and heat
- ↑ Vascular permeability → protein-rich exudate → swelling
- Slowing of blood flow (stasis) → haemoconcentration
Cellular Events
- Margination and rolling (selectins)
- Adhesion (integrins-ICAM) and transmigration (diapedesis)
- Chemotaxis — C5a, LTB4, IL-8, bacterial products
- Phagocytosis — recognition, engulfment, killing (respiratory burst)
- Neutrophils predominate in the first 24 hours
Vascular changes deliver fluid and cells to the site of injury. Sign Mechanism Redness, heat Vasodilatation Swelling Exudate Pain Mediators (bradykinin, PG) Applied
- Outcomes: resolution, abscess, healing by fibrosis, or chronic inflammation
- Defective adhesion → leucocyte adhesion deficiency
🔑KEY POINTS TO REMEMBER- Acute inflammation = vascular (vasodilatation, ↑ permeability) + cellular (neutrophils) response.
- Steps: margination, adhesion, transmigration, chemotaxis, phagocytosis.
- Outcomes: resolution, abscess, fibrosis or chronic inflammation.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Chemical mediators are substances released from cells or plasma that initiate and amplify the inflammatory response.
Cell-Derived Mediators
- Vasoactive amines — histamine (mast cells), serotonin: vasodilatation, ↑ permeability
- Arachidonic acid metabolites — prostaglandins (pain, fever, vasodilatation), leukotrienes (chemotaxis, bronchospasm)
- Cytokines — TNF, IL-1 (fever, acute-phase response), IL-8 (chemotaxis)
- Nitric oxide — vasodilatation, microbicidal
- Lysosomal enzymes, platelet-activating factor, free radicals
Plasma-Derived Systems
- Complement — C3a/C5a (anaphylatoxins), C5a (chemotaxis), C3b (opsonin), C5b-9 (lysis)
- Kinin system — bradykinin: pain, vasodilatation, ↑ permeability
- Coagulation and fibrinolytic systems — thrombin, plasmin
Mediators translate injury into the vascular and cellular response. Effect Mediator Vasodilatation Histamine, PGI₂, NO Pain Bradykinin, PGE₂ Chemotaxis C5a, LTB4, IL-8 Fever IL-1, TNF, PGE₂ Applied
- NSAIDs act by inhibiting prostaglandin synthesis
- Antihistamines block the early vascular phase
🔑KEY POINTS TO REMEMBER- Mediators are cell-derived (amines, prostaglandins, cytokines, NO) or plasma-derived.
- Plasma systems: complement, kinin, coagulation, fibrinolytic.
- C5a and LTB4 are chemotactic; bradykinin and PGE₂ cause pain.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Chronic inflammation is prolonged inflammation in which active inflammation, tissue destruction and repair proceed simultaneously.
Causes
- Persistent infection — tuberculosis, leprosy, syphilis, fungi
- Prolonged exposure to toxic agents — silica, foreign bodies
- Autoimmune disease — rheumatoid arthritis, lupus
- Following unresolved acute inflammation
Cells & Features
- Macrophages — dominant cell (activated by IFN-γ)
- Lymphocytes, plasma cells, eosinophils, mast cells
- Tissue destruction and fibrosis (repair) together
- Angiogenesis and new connective tissue
Simultaneous destruction and repair distinguish it from acute inflammation. Feature Acute Chronic Onset Rapid Insidious Main cell Neutrophil Macrophage Fibrosis Absent Prominent Applied
- Macrophage-lymphocyte cross-talk sustains the process
- Chronic inflammation predisposes to amyloidosis and malignancy
🔑KEY POINTS TO REMEMBER- Chronic inflammation shows simultaneous inflammation, destruction and repair.
- Macrophage is the dominant cell, with lymphocytes and plasma cells.
- Causes: persistent infection, toxic agents, autoimmunity.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Granulomatous inflammation is chronic inflammation in which macrophages transform into epithelioid cells forming discrete nodular collections called granulomas.
Components
- Epithelioid cells — activated macrophages with abundant pink cytoplasm
- Giant cells — Langhans (peripheral horseshoe nuclei) or foreign-body type
- Surrounding lymphocyte cuff and fibroblasts
- ± Central caseous necrosis
Causes
- Infective — tuberculosis, leprosy, syphilis (gumma), fungal, schistosomiasis
- Non-infective — sarcoidosis, Crohn disease, berylliosis, silicosis
- Foreign body — suture, talc
The body isolates what it cannot destroy inside a granuloma. Type Necrosis Example Caseating Present Tuberculosis Non-caseating Absent Sarcoidosis Applied
- Granuloma with caseation → look for acid-fast bacilli
- Sarcoid granulomas contain Schaumann and asteroid bodies
🔑KEY POINTS TO REMEMBER- Granuloma = epithelioid cells, giant cells and lymphocytes.
- T-cell (IFN-γ) mediated, or foreign-body type.
- Caseating in TB; non-caseating in sarcoidosis and Crohn disease.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Repair restores tissue integrity after injury by regeneration (same cell type) or fibrosis (scar formation).
Phases of Healing
- Inflammatory (0–3 days) — clot, neutrophils then macrophages
- Proliferative (3–14 days) — granulation tissue: angiogenesis, fibroblasts, collagen III
- Maturation/remodelling (weeks–months) — collagen III replaced by collagen I, ↑ tensile strength
Granulation Tissue
- New capillaries + fibroblasts + inflammatory cells
- Pink, soft, granular, bleeds easily
- Hallmark of healing
Granulation tissue bridges the gap and matures into a scar. Time Event Day 0–3 Inflammation Day 3–14 Granulation tissue Weeks–months Remodelling Applied
- Wound regains only ~70–80% of original strength
- Complications: keloid, hypertrophic scar, contracture, dehiscence
🔑KEY POINTS TO REMEMBER- Repair by regeneration or fibrosis; three phases of healing.
- Granulation tissue = new capillaries + fibroblasts, the hallmark of repair.
- Collagen III is replaced by collagen I during remodelling.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
The cardinal signs of inflammation are the classic clinical features of the acute inflammatory response, described by Celsus and Virchow.
The Five Signs
- Rubor (redness) — vasodilatation, ↑ blood flow
- Calor (heat) — ↑ blood flow
- Tumor (swelling) — exudate from ↑ vascular permeability
- Dolor (pain) — bradykinin, PGE₂, pressure on nerve endings
- Functio laesa (loss of function) — added by Virchow
Each sign maps directly onto an underlying vascular or chemical change. Sign Mechanism Rubor Vasodilatation Tumor Exudate Dolor Bradykinin, PGE₂ Applied
- Systemic effects: fever, leucocytosis, ↑ acute-phase proteins (CRP, ESR)
- Signs may be muted in immunosuppressed or elderly patients
🔑KEY POINTS TO REMEMBER- Five signs: rubor, calor, tumor, dolor, functio laesa.
- Redness and heat from vasodilatation; swelling from exudate.
- Pain is mediated by bradykinin and prostaglandin E₂.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Exudate is protein-rich inflammatory fluid, while transudate is protein-poor fluid resulting from altered hydrostatic or osmotic pressure.
Exudate
- Due to ↑ vascular permeability (inflammation)
- High protein (>3 g/dL), specific gravity >1.020
- Cells present; clots (contains fibrinogen)
- Examples: pus, pleural effusion in pneumonia or tuberculosis, peritonitis
Transudate
- Due to ↑ hydrostatic or ↓ oncotic pressure
- Low protein (<3 g/dL), specific gravity <1.012
- Few cells; does not clot; clear fluid
- Examples: cardiac failure, nephrotic syndrome, cirrhosis (ascites)
Protein content reflects whether vessel walls are leaky or intact. Feature Exudate Transudate Protein >3 g/dL <3 g/dL Specific gravity >1.020 <1.012 Clotting Yes No Applied
- Light’s criteria distinguish the two in pleural effusion
- Determines whether to investigate for infection or heart failure
🔑KEY POINTS TO REMEMBER- Exudate: inflammatory, protein-rich, high specific gravity, clots.
- Transudate: pressure-related, protein-poor, does not clot.
- Light’s criteria are used clinically for pleural fluid.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Granulomatous inflammation is chronic inflammation in which macrophages transform into epithelioid cells forming discrete nodular collections called granulomas.
Components
- Epithelioid cells — activated macrophages with abundant pink cytoplasm
- Giant cells — Langhans (peripheral horseshoe nuclei) or foreign-body type
- Surrounding lymphocyte cuff and fibroblasts
- ± Central caseous necrosis
Causes
- Infective — tuberculosis, leprosy, syphilis (gumma), fungal, schistosomiasis
- Non-infective — sarcoidosis, Crohn disease, berylliosis, silicosis
- Foreign body — suture, talc
The body isolates what it cannot destroy inside a granuloma. Type Necrosis Example Caseating Present Tuberculosis Non-caseating Absent Sarcoidosis Applied
- Granuloma with caseation → look for acid-fast bacilli
- Sarcoid granulomas contain Schaumann and asteroid bodies
🔑KEY POINTS TO REMEMBER- Granuloma = epithelioid cells, giant cells and lymphocytes.
- T-cell (IFN-γ) mediated, or foreign-body type.
- Caseating in TB; non-caseating in sarcoidosis and Crohn disease.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Multinucleate giant cells are formed by the fusion of macrophages or other cells in chronic inflammation and tumours.
Inflammatory Giant Cells
- Langhans giant cell — nuclei arranged in a peripheral horseshoe; tuberculosis
- Foreign-body giant cell — nuclei scattered haphazardly; suture, talc
- Touton giant cell — ring of nuclei with foamy cytoplasm; xanthoma, fat necrosis
- Warthin-Finkeldey cell — measles
Tumour Giant Cells
- Reed-Sternberg cell — Hodgkin lymphoma (owl-eye, mirror-image nuclei)
- Osteoclast-like giant cells — giant cell tumour of bone
- Anaplastic tumour giant cells — pleomorphic, hyperchromatic
Fusion creates a cell better able to engulf large particles. Giant cell Nuclei Setting Langhans Horseshoe Tuberculosis Foreign body Scattered Suture, talc Reed-Sternberg Owl-eye Hodgkin lymphoma Applied
- Langhans cells are a clue to tuberculosis
- Reed-Sternberg cell is essential for diagnosing Hodgkin lymphoma
🔑KEY POINTS TO REMEMBER- Giant cells form by fusion of macrophages.
- Langhans (horseshoe nuclei) in TB; foreign-body type has scattered nuclei.
- Reed-Sternberg cells characterise Hodgkin lymphoma.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Wounds heal by first intention when edges are apposed, and by second intention when there is a large tissue defect.
First (Primary) Intention
- Clean, sutured surgical incision with apposed edges
- Minimal tissue loss; small clot and little granulation tissue
- Rapid healing, thin linear scar
- Minimal wound contraction; low infection risk
Second Intention
- Large open wound, ulcer, burn, abscess cavity
- Extensive tissue loss → abundant granulation tissue
- Marked wound contraction (myofibroblasts) — up to 80% reduction
- Slow healing, large irregular scar, higher infection and contracture risk
The size of the tissue defect dictates the pattern of healing. Feature First Second Tissue loss Minimal Extensive Granulation tissue Scanty Abundant Scar Thin Large Contraction Minimal Marked Applied
- Contraction after burns causes disabling contractures
- Debridement and closure convert second to first intention healing
🔑KEY POINTS TO REMEMBER- First intention: apposed edges, scanty granulation tissue, thin scar.
- Second intention: tissue gap, abundant granulation tissue, marked contraction.
- Wound contraction is mediated by myofibroblasts.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Wound healing is influenced by local and systemic factors that either promote or delay repair.
Local Factors
- Infection — the single most important cause of delay
- Poor blood supply and oxygenation
- Foreign body, necrotic tissue, haematoma
- Movement of the wound; type and size of wound
- Ionising radiation
Systemic Factors
- Nutrition — protein and vitamin C (collagen cross-linking), zinc
- Diabetes mellitus — microangiopathy, infection risk
- Steroids — inhibit collagen synthesis and inflammation
- Age, anaemia, malignancy, uraemia, chemotherapy
Both local conditions and the patient’s general state govern healing. Factor Effect Infection Major delay Vitamin C deficiency Weak collagen Steroids ↓ Collagen synthesis Applied
- Optimise glycaemic control before elective surgery
- Complications of poor healing: dehiscence, incisional hernia, ulceration
🔑KEY POINTS TO REMEMBER- Infection is the most important local cause of delayed healing.
- Systemic: malnutrition, vitamin C deficiency, diabetes, steroids, age.
- Poor healing leads to dehiscence and incisional hernia.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Tissues are classified by their regenerative capacity into labile, stable and permanent cell populations.
Labile Cells
- Continuously dividing throughout life
- Surface epithelia — skin, gut, respiratory tract, urinary tract
- Bone marrow haematopoietic cells
- Excellent regeneration
Stable and Permanent Cells
- Stable (quiescent) — normally in G0, divide when stimulated: liver, kidney tubules, pancreas, fibroblasts, endothelium, smooth muscle
- Permanent — cannot divide: neurons, cardiac muscle, skeletal muscle
- Permanent tissue injury heals by scar formation only
Only dividing cell populations can truly regenerate. Type Example Healing Labile Skin, gut Regeneration Stable Liver Regeneration if stimulated Permanent Neuron, myocardium Scar Applied
- Myocardial infarct heals by fibrous scar, not new muscle
- The liver regenerates remarkably after partial hepatectomy
🔑KEY POINTS TO REMEMBER- Labile cells divide continuously (skin, gut, marrow).
- Stable cells divide when stimulated (liver, kidney tubules).
- Permanent cells (neurons, cardiac muscle) heal only by scarring.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.