Pathology of Repair PDF

Pathology of Repair By Prof. Mie Ali Dr. Mona Younis Pathology Department-Faculty of Medicine Mansoura University  REPAIR Definition: replacement of damaged tissue by new healthy one. Types of repair: A)Classical types: 1) Regenerati...

Pathology of Repair By Prof. Mie Ali Dr. Mona Younis Pathology Department-Faculty of Medicine Mansoura University  REPAIR Definition: replacement of damaged tissue by new healthy one. Types of repair: A)Classical types: 1) Regeneration. 2) Fibrosis (Gliosis in CNS). B)Other types: Organization. What determine the type of repair? 1) Type of damaged cells. 2) The supporting framework. 1) Type of damaged cells: a- Labile cells: continuously dividing cells & if damaged, it heals by regeneration. e.g. - Epidermis & mucous membrane (any epithelial cells) - Blood & lymphoid tissue. b- Permanent cells: Cells that don't proliferate at all e.g.: - Muscle cells & if damaged, it heals by fibrosis. - Nerve cells & if damaged, it heals by gliosis. c- Stable cells: They can proliferate with limited capacity (not proliferate under normal condition but if damaged they can heal by mixed regeneration &/or fibrosis). e.g. -Parenchymal cells: liver cells, kidney tubular cells & endocrine & exocrine glands. -Mesenchymal cells: fibroblasts, osteoblasts & chondroblasts. 2) Supporting framework: if the normal framework of organ is intact, healing by regeneration occur. if the normal framework of organ is destroyed, the proliferating cells may grow in a disorganized pattern (improper regeneration mixed with fibrosis) e.g. liver cirrhosis  Phases of healing healing of any tissue occurs through the following phases: 1) Cleaning phase: cleaning the area with removal of necrotic debris by phagocytic cells. 2) Proliferation phase: cells responsible for repair proliferate to replace the damaged ones. 3) Re-modeling phase: maturation of the new tissue trying to simulate the original one. (A) Healing by Regeneration  Regeneration Definition: Replacement of the damaged tissue by healthy tissue of the same kind. Cells that heal by regeneration are: 1) Labile cells. 2) Stable cells (with intact normal framework).  1) Healing in the Skin a- Damage of epidermis only ----- Regeneration. b- Damage of the epithelium & sub- epithelium ----- Fibrosis with loss of hair follicles, sweat & sebaceous glands. 2) Healing of Liver Damage - If the supporting framework is intact (mild damage) ----- regeneration. - If the framework is destroyed (severe damage) ----- cirrhosis (fibrosis with loss of architecture).  3) Healing of bone fracture A- Cleaning phase:- after fracture, blood and necrotic debris between the fracture ends are cleaned by Macrophages & Osteoclasts. B- Proliferation phase:- Granulation tissue formation:- A modified type of granulation tissue develops between the fracture ends formed of (capillaries, Fibroblasts & osteoblasts).  Formation of provisional callus:- - The capillaries provide O2 & nutrients to the area of repair. - Fibroblasts start to form collagen of bone. - Osteoblasts form the bone matrix. This tissue is devoid of minerals (soft) uniting the fracture ends osteoid (soft callus) & formed of internal, external & intermediate callus. - Osteoblasts starts to secrete alkaline phosphatase with mineral deposition in the soft callus to become hard callus (osseous) but immature woven bone with complete union of the fracture. C) Remodeling:- - The unnecessary callus (internal & external) are removed by osteoclasts leaving the permanent Intermediate callus to become mature (lamellar) bone & regeneration of the bone marrow occurs. * Causes of Failure of bony union: 1) Poor immobilization of the fractured ends ---- Fibrous union. 2) Interposition of soft tissue (muscle or fascia) ----Non- union. 3) No good apposition ---- mal-union 4) Other factors --- delayed union e.g. - Pathological fracture caused by bone disease. - Poor blood supply. - Infection. - Old age. - Malnutrition. (B) Healing by Fibrosis (Gliosis in CNS) Definition: Replacement of the damaged tissue by granulation tissue that matures into fibrous tissue. In CNS gliosis occurs instead of fibrosis.  Mechanism of fibrosis (Formation of Granulation Tissue) Definition: granulation tissue is a transient tissue formed during the repair by fibrosis. Composition: It is formed of two components, Capillaries & fibroblasts. Mechanism of formation: (1)The capillaries --- Neo-vascularization (Angiogenesis): endothelial cells derived from the healthy capillaries in the edge of damaged area, Then migrate & proliferate to form solid endothelial buds that become canalized ---- new capillaries without basement membrane --- bring nutrition to proliferating fibroblasts. (2) Fibroblasts:- derived from the resting fibrocytes in the edge of damaged area --- activated to fibroblasts --- secrete collagen. N.B. Granulation tissue formation is mediated by chemical substances known as "growth factors". N/E (Characters): * insensitive, * granular, * pink, * moist due to excess fluid exudates, * bleeds easily & * resistant to infection (excess macrophages). M/E: - Capillaries. - Fibroblasts. Fate: 1) Maturation: fibroblasts secrete collagen --- compress & obliterate capillaries --- decrease vascularity. 2) Fibroblasts acquire actin & myosin filaments --- contraction of wound edges --- decrease its size. 3) Collagen fibers undergo remodeling to remove the unnecessary fibers in different directions. 4) Fibroblasts change into resting fibrocytes. 5) Finally avascular strong fibrous (scar) is produced. Examples of healing by fibrosis (gliosis): 1) Muscle: Damage of the muscles (e.g. in myocardial infarction) --- fibrosis. 2) Nerves & neurones: Damage of the CNS heals by gliosis. Healing by organization * Def: Healing of dead or non-living material by Granulation tissue --- Fibrous tissue. * Examples: - Thrombus. - Fibrin in Sero-fibrinous inflammation. Healing of skin wounds Healing of skin wounds may occur by one of two mechanisms depending on the type of the wound : 1- Primary union of 2- Secondary union of wound (Healing by first wounds (Healing by intention): second intention): Occurs in a clean incised Occurs in gaping wounds, wound with minimal septic wound or tissue destruction, and abscesses with marked when the edges are tissue destruction, and approximated when the edges are away e.g. surgical wounds. from each other. Complications of Repair  {I} Complications due to too less repair:- 1) Ulcer. 2) Sinus. 3) Fistula. 4) Weak scar in abdominal operations --- Incisional hernia. 5) Fibrous union of bone --- Pseudo-arthrosis. Too less repair Ulcer. Sinus. Fistula.  {II} Complications due to excessive repair:- 1- Excessive granulation tissue which protrudes above the level of adjacent skin. 2- Excessive scar tissue which protrudes above the level of adjacent skin. 3- Squamous cell carcinoma rarely develops in a scar. 4- fibrosis can harm the patient: Cerebral scar may cause cerebral irritation and epilepsy. Scarring of heart valves will result in stenosis. 5- Keloid:- Is a big projecting scar covered by intact stretched epidermis caused by collagenase deficiency. It recurs after surgical excision. Factors affecting Repair  {I} Local factors:- 1) Adequacy of blood supply to the injured area (sufficient or not). 2) Presence of F.B. or large hematoma: helps bacterial growth & delay repair 3) Presence of infection --- delay repair. 4) Types of cells in injured tissue: *Labile & stable cells --- healing by regeneration. *Permanent cells --- ends by scarring. 5) Size of the wound: Large wound takes a longer time for repair. 6) Excessive mobilization: In bone fractures: Improper fixation --- mal- or non-union  {II} Systemic Factors:- 1) Age of the patient: *Young age --- rapid healing. *Old age --- delayed healing. 2) Nutritional status: Malnutrition --- delays healing. For good healing, the patient needs: - Proteins. - Vit C. (helps collagen synthesis). - Zinc (important enzymes actions). 3) Debilitating diseases: - Diabetes Mellitus: increases the susceptibility to infections & decrease phagocytic activity --- delay healing. - Malignant tumors: delay wound healing due to Cancer cachexia --- decrease body resistance. 4) Administration of drugs: * Corticosteroids --- delay wound healing * Anabolic steroids (testosterone) & insulin --- help healing