PATHOLOGY—INFLAMMATION

PATHOLOGY—INFLAMMATION
Apoptosis Programmed cell death; ATP required. Mediated by caspases. Characterized by cell shrinkage, chromatin condensation (pyknosis), membrane blebbing, DNA fragmentation (karyorrhexis), nuclear fragmentation (karyolysis), and formation of apoptotic bodies, which are then phagocytosed. No significant inflammation. Occurs during embryogenesis, hormone induction (menstruation), immune cell– mediated death, injurious stimuli (e.g., radiation, hypoxia), atrophy (e.g., endometrial lining during menopause).
Necrosis Enzymatic degradation of a cell resulting from exogenous injury. Characterized by enzymatic digestion and protein denaturation, with release of intracellular components. Inflammatory. Morphologically occurs as coagulative (heart, liver, kidney), liquefactive (brain), caseous (tuberculosis), fat (pancreas), fibrinoid (blood vessels), or gangrenous (limbs, GI tract).
Cell injury Reversible Irreversible Cellular swelling Plasma membrane damage Nuclear chromatin clumping Lysosomal rupture ↓ATP synthesis Ca2+ influx→oxidative phosphorylation Ribosomal detachment Nuclear pyknosis, karyolysis, karyorrhexis Glycogen depletion Mitochondrial permeability Fatty change
Inflammation Characterized by rubor (redness), dolor (pain), calor (heat), tumor (swelling), and functio laesa (loss of function). Fluid exudation ↑vascular permeability, vasodilation, endothelial injury. Leukocyte activation Emigration (rolling, tight binding, diapedesis); chemotaxis (bacterial products, complement, chemokines); phagocytosis and killing. Fibrosis Fibroblast emigration and proliferation; deposition of ECM. Acute Neutrophil, eosinophil, and antibody mediated. Chronic Mononuclear cell mediated: Characterized by persistent destruction and repair. Granuloma––nodular collections of epithelioid Granulomatous diseases: TB macrophages and giant cells. (caseating), syphilis, leprosy, Resolution Restoration of normal structure. Bartonella, some fungal Granulation tissue––highly vascularized, fibrotic. pneumonias, sarcoidosis, Abscess––fibrosis surrounding pus. Crohn’s disease. Fistula––abnormal communication. Scarring––collagen deposition resulting in altered structure and function.
HIGH-YIELD PRINCIPLES PATHOLOGY
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PATHOLOGY—INFLAMMATION (continued)
Transudate vs. Transudate Exudate exudate Hypocellular Cellular Protein poor Protein rich Specific gravity < 1.012 Specific gravity > 1.020 Due to: Due to: ↑hydrostatic pressure Lymphatic obstruction ↑oncotic pressure Inflammation Na+ retention
Leukocyte Neutrophils exit from blood vessels at sites of tissue injury and inflammation in 4 steps: extravasation 1. Rolling––mediated by E-selectin and P-selectin on vascular endothelium binding to sialyl LewisX on the leukocyte 2. Tight binding––mediated by ICAM-1 on vascular endothelium binding to LFA-1 (Integrin) on the leukocyte 3. Diapedesis––leukocyte travels between endothelial cells and exits blood vessel 4. Migration––leukocyte travels through the interstitium to the site of injury or infection guided by chemotactic signals (e.g., cytokines)
Free radical injury Initiated via radiation exposure, metabolism of drugs (phase I), redox reaction, nitric oxide, transition metals, leukocyte oxidative burst. Induces cell injury through membrane lipid peroxidation, protein modification, DNA breakage. Free radical degradation produced through enzymes (catalase, superoxide dismutase, glutathione peroxidase), spontaneous decay, antioxidants (vitamins E and A). Reperfusion after anoxia induces free radical production (e.g., superoxide) and is a major cause of injury after thrombolytic therapy.