Master Pathology
for FMGE

Core Concepts

Pathology is the study of disease, focusing on its causes (etiology), mechanisms (pathogenesis), morphological changes, and clinical manifestations.

• Cell Injury & Adaptation:
  • Reversible Injury: Cellular swelling (hydropic change), fatty change (steatosis). Key features: plasma membrane intact, mitochondrial function reversible.
  • Irreversible Injury (Necrosis): Loss of membrane integrity, enzyme leakage, nuclear changes (pyknosis, karyorrhexis, karyolysis).
    • Coagulative: Most common, characteristic of ischemia/infarcts (except brain). Architecture preserved. E.g., Myocardial infarct.
    • Liquefactive: Associated with infection (abscess) or cerebral infarcts. Digestion of dead cells into viscous liquid. E.g., Brain infarct, bacterial infection.
    • Caseous: Fragmented cells and amorphous granular debris, characteristic of tuberculosis (granuloma). "Cheese-like."
    • Fat Necrosis: Enzymatic digestion of fat (e.g., acute pancreatitis) or traumatic (breast). Produces chalky white areas (saponification).
    • Fibrinoid: Seen in immune reactions involving blood vessels (e.g., vasculitis, malignant hypertension). Deposition of antigen-antibody complexes and fibrin.
    • Gangrenous: Often refers to ischemic necrosis of a limb, typically lower extremity. Can be 'dry' (coagulative) or 'wet' (liquefactive due to superimposed bacterial infection).
  • Apoptosis: Programmed cell death. Energy-dependent, controlled process, no inflammation. E.g., embryogenesis, endometrial shedding, viral hepatitis (Councilman bodies).
  • Adaptations: Atrophy, hypertrophy, hyperplasia, metaplasia (reversible change of one adult cell type to another), dysplasia (disordered growth, often pre-neoplastic).
• Inflammation:
  • Acute: Rapid onset, short duration. Cardinal signs (rubor, tumor, calor, dolor, functio laesa). Predominant cells: Neutrophils. Mediators: Histamine, Prostaglandins, Leukotrienes, Bradykinin, Complement (C3a, C5a). Outcomes: Resolution, healing by fibrosis, chronic inflammation, abscess formation.
  • Chronic: Prolonged, weeks to years. Predominant cells: Macrophages, lymphocytes, plasma cells. Associated with tissue destruction and repair (fibrosis). Granulomatous inflammation (e.g., TB, sarcoidosis, Crohn's) is a form of chronic inflammation with epithelioid macrophages, giant cells, and lymphocytes.
• Repair & Healing:
  • Regeneration: Replacement of damaged cells with original cell type (e.g., skin, liver).
  • Repair (Fibrosis): Replacement by connective tissue (scar formation). Involves granulation tissue (fibroblasts, blood vessels, inflammatory cells).
  • Wound Healing: Primary intention (clean, incised wounds, minimal scar) vs. Secondary intention (large defects, infection, prominent granulation tissue, contraction, large scar).
• Hemodynamic Disorders:
  • Edema: Excess fluid in interstitial tissue or body cavities. Causes: Increased hydrostatic pressure, decreased oncotic pressure, lymphatic obstruction, increased vascular permeability, sodium retention. Transudate (protein-poor) vs. Exudate (protein-rich).
  • Thrombosis: Intravascular blood clot formation. Virchow's Triad: Endothelial injury, abnormal blood flow (stasis/turbulence), hypercoagulability.
  • Embolism: Intravascular solid, liquid, or gaseous mass carried by blood to a distant site. Types: Pulmonary (most common from DVT), Systemic (from cardiac mural thrombi), Fat (bone fractures), Air, Amniotic fluid.
  • Infarction: Ischemic necrosis caused by occlusion of arterial supply or venous drainage. White (anemic) infarcts (solid organs) vs. Red (hemorrhagic) infarcts (venous occlusion, loose tissues, organs with dual blood supply).
  • Shock: Systemic hypoperfusion due to reduced cardiac output or effective circulating blood volume. Types: Cardiogenic, Hypovolemic, Septic, Anaphylactic, Neurogenic.
• Neoplasia:
  • Benign vs. Malignant:
    • Benign: Well-differentiated, slow growth, cohesive, encapsulated, no invasion/metastasis.
    • Malignant: Anaplasia (loss of differentiation), rapid/erratic growth, invasive, metastatic potential.
  • Terminology: Carcinoma (epithelial origin), Sarcoma (mesenchymal origin), Lymphoma/Leukemia (hematopoietic).
  • Oncogenes: Mutated proto-oncogenes, promote cell growth (e.g., RAS, MYC, HER2/neu).
  • Tumor Suppressor Genes: Inhibit cell growth; mutation leads to uncontrolled growth (e.g., p53, Rb).
  • Grading: Based on differentiation (microscopic appearance). G1 (well), G2 (mod), G3 (poor), G4 (undifferentiated).
  • Staging (TNM): Based on tumor size (T), nodal involvement (N), metastasis (M). Clinical staging determines treatment and prognosis.
  • Paraneoplastic Syndromes: Symptoms distant from tumor or its metastases, caused by tumor products (e.g., Cushing's from SCLC, SIADH, Hypercalcemia from PTHrP).
• Immunopathology:
  • Hypersensitivity Reactions:
    • Type I (Anaphylactic): IgE-mediated, immediate. E.g., asthma, allergies, anaphylaxis.
    • Type II (Cytotoxic): Antibody (IgG/IgM) directed against cell surface antigens. E.g., Transfusion reactions, autoimmune hemolytic anemia.
    • Type III (Immune Complex): Antigen-antibody complexes deposit in tissues. E.g., SLE, Post-streptococcal glomerulonephritis, Arthus reaction.
    • Type IV (Delayed-type/Cell-mediated): T-cell mediated. E.g., Contact dermatitis, TB skin test, Type 1 Diabetes, Graft rejection.
  • Autoimmune Diseases: Breakdown of self-tolerance, immune attack on own tissues. E.g., SLE, RA, Hashimoto's thyroiditis.

Clinical Presentation

• Inflammation: Acute (redness, heat, swelling, pain, loss of function); Chronic (persistent symptoms, fibrosis leading to organ dysfunction).
• Thrombosis/Embolism: Deep vein thrombosis (DVT) -> limb swelling, pain; Pulmonary embolism (PE) -> sudden dyspnea, chest pain, hemoptysis; Myocardial infarction -> chest pain radiating to arm/jaw.
• Neoplasia: Palpable mass, unexplained weight loss, fever, fatigue, night sweats (constitutional symptoms, esp. in lymphomas), organ dysfunction due to invasion/compression, paraneoplastic syndromes.
• Edema: Swelling (pitting vs. non-pitting), shortness of breath (pulmonary edema), ascites, anasarca.
• Shock: Hypotension, tachycardia, cold clammy skin (except septic shock: warm skin), altered mental status, oliguria.

Diagnosis (Gold Standard)

The definitive diagnosis in pathology often relies on morphological examination of tissue.

• Biopsy & Histopathology: Microscopic examination of tissue (e.g., excisional, incisional, core needle biopsy). Provides definitive diagnosis for most neoplastic and inflammatory conditions.
• Cytology: Microscopic examination of individual cells (e.g., Pap smear, Fine Needle Aspiration Cytology - FNAC, effusions). Useful for screening and preliminary diagnosis.
• Immunohistochemistry (IHC): Uses specific antibodies to detect antigens on cells (e.g., tumor markers, cell origin). Crucial for tumor classification and prognostication.
• Molecular Diagnostics: PCR, FISH, sequencing for genetic mutations, chromosomal translocations (e.g., CML - BCR-ABL, EGFR mutations in lung cancer).
• Autopsy: Post-mortem examination to determine cause of death and disease progression.

Management (First Line)

Pathological diagnosis guides appropriate medical or surgical intervention.

• Inflammation: Identify and remove the inciting agent (e.g., antibiotics for infection); anti-inflammatory drugs (NSAIDs, corticosteroids) for symptomatic relief.
• Thrombosis: Anticoagulation (heparin, warfarin, DOACs) to prevent extension and embolism; thrombolysis in selected cases.
• Neoplasia:
  • Benign Tumors: Surgical excision if symptomatic or cosmetically indicated.
  • Malignant Tumors: Surgery (mainstay for solid tumors), Chemotherapy, Radiotherapy, Targeted therapy, Immunotherapy, or combinations thereof, based on tumor type, stage, and patient factors.
• Edema: Address underlying cause (e.g., diuretics for cardiac failure, albumin for hypoalbuminemia).
• Shock: Aggressive fluid resuscitation, vasopressors, address underlying cause (e.g., antibiotics for septic shock, revascularization for cardiogenic shock).