Tissue Repair PDF

Tissue repair Dr Bhavta Harrielall Department of Anatomical Pathology Date: 21 January 2025 Objectives Know the following: 1. Definition of tissue repair 2. Forms of tissue repair: Regeneration Scarring 3. Steps involved in eac...

Tissue repair Dr Bhavta Harrielall Department of Anatomical Pathology Date: 21 January 2025 Objectives Know the following: 1. Definition of tissue repair 2. Forms of tissue repair: Regeneration Scarring 3. Steps involved in each form of tissue repair Definition of repair Also known as healing The restoration of tissue architecture and function after tissue injury Refers to two types: 1. Regeneration 2. Scarring Types of tissue repair Cell restoration Proliferative capacity Regeneration Restores normal cells Cells with capacity to proliferate Scarring Connective tissue Cells without capacity to deposition proliferate If tissue severely damaged, Even if able to proliferate Regeneration Components returning to normal state Occurs by proliferation of residual cells Connective tissue deposition (Scar formation) Laying down of fibrous tissue that may result in a scar When tissue are incapable of complete restitution If supporting structures are severely damaged Fibrosis: extensive deposition of collagen as a consequence of chronic inflammation: lungs, liver, kidney Organisation: fibrosis in a tissue space occupied by an inflammatory exudate. Cell & Tissue Regeneration Cell proliferation Growth factors Critically dependent on: - Integrity of the extracellular matrix - Development of mature cells from stem cells. Intrinsic proliferative capacity. 3 groups of tissue types 1. Labile tissues (continuously dividing) Eg. Haemopoietic cells, surface epithelia Readily regenerative after injury 2. Stable tissues (quiescent) Eg, cells of solid organs like liver Proliferate only in response to injury or loss 3. Permanent tissues(terminally differentiated) Eg. Neurons/myocardium Injury is irreversible and results in scar Signals of cell proliferation: Growth factors Multiple cell types/ cell-selective. Produced by cells near the site of damage. - Mainly Macrophages - Epithelial & stromal cells Signaling pathways: proteins : cell cycle & release blocks on checkpoints. Tissue stem cells Supplement proliferation of residual cells Live in specialized niches Triggered by injury Differentiate into mature cells that repopulate the injured tissue.  Repair by Connective Tissue Deposition (Scar formation) A response that “patches” rather than restores the tissue. If repair cannot be accomplished by regeneration alone In combination with regeneration If the tissue injury is: Severe or chronic To parenchymal cells/epithelia + connective tissue framework In non-dividing cell Steps in scar formation Angiogenesis - Formation of new blood vessels, - Supplying nutrients and oxygen: supporting repair. Formation of granulation tissue: - Pink, soft, granular gross appearance. - Migration + proliferation of fibroblasts - Deposition of loose connective tissue, together with the vessels & leukocytes Remodeling of connective tissues -Production of a stable fibrous scar Deposition of Connective Tissue Two steps: 1. Migration & proliferation of fibroblasts into the site of injury 2. Deposition of ECM proteins produced by these cells. Orchestrated by: Cytokines & Growth factors - TGF-β (Transforming growth factor-β): most important cytokine - PDGF, FGF-2 Remodelling of connective tissue Outcome of repair: Synthesis Vs degradation of ECM proteins. After its deposition, the connective tissue in the scar continues to be modified and remodeled. The degradation of collagens and other ECM components - Family of matrix metalloproteinases (MMPs),(metal ions (e.g. zinc) - Produced: fibroblasts, macrophages, neutrophils, synovial cells, and some epithelial cells) - Synthesis & secretion: growth factors, cytokines & other agents. Healing of Skin wounds First intention/primary union Second intention/secondary union References Kumar, V., Abbas, A.K. & Aster,J.C. Robbins and Cotran pathologic basis of disease (10th edition). Philadelphia, PA: Elsevier/Saunders.