4. Tissue Injury & Repair Flashcards
Introduction
Homeostasis Injury Excessive physiologic stresses or adverse pathologic stimuli Adaptation Reversible injury Irreversible injury + cell death
Cellular Adaptation (1)
Increased demand/stimulation = hypertrophy, hyperplasia
Cellular Adaptation (2)
Decreased nutrients/stimulation = atrophy
Cellular Adaptation (3)
Chronic irritation = metaplasia
Cellular Injury
Acute and transient stimuli e.g. hypoxia, chemical injury, microbial infection Reversible injury Irreversible injury cell death Apoptosis Necrosis
Causes of Cellular Injury
Hypoxia Physical agents Chemical agents Infectious agents Immunologic reactions Genetic derangements Nutritional imbalances
Mechanisms of Cellular Injury
ATP depletion Mitochondrial damage Increased intracellular Ca2+ Oxidative stress Membrane damage DNA and protein damage
Tissue Regeneration & Repair
Regeneration: complete reconstitution
Tissues with high proliferative capacity
Requires viable stem cells and intact connective tissue scaffolding
Repair: combination of regeneration and scar formation
Relative contribution of two processes depends on capacity to regenerate, extent of injury, and extent of scarring/fibrosis
Mechanisms of Regeneration
Amphibians versus Mammals
Limited examples of true regeneration
Epithelium following superficial skin injury
Bone following fracture
Mostly compensatory
Hypertrophy (e.g. nephrons following nephrectomy)
Hyperplasia (e.g. hepatocytes following partial hepatectomy)
Healing by Repair, Scarring, Fibrosis
Severe tissue injury with damage to parenchyma and stroma
Fibro-proliferative response
Deposition of collagen and ECM components (scar)
“Patches” tissue
Persistent damage chronic inflammation fibrosis
Sequence of Healing
Inflammation Angiogenesis/Neovascularization Migration and proliferation of parenchymal cells and fibroblasts Scar formation Connective tissue remodeling
Factors Affecting Wound Healing
Local Factors Size Location (i.e. how well vascularised) Type (infectious/necrotic/traumatic) Infections, mechanical forces, foreign bodies delay healing
Systemic Factors Nutritional status Metabolic status (e.g. diabetes mellitus) Circulatory/vascular status Hormones (e.g. glucocorticoids)
Complications of Repair
Deficient scar formation
Excessive repair
Excessive granulation tissue (proud flesh)
Excessive collagen accumulation hypertrophic scar
Keloid
Formation of contractures