Healing and Repair

Repair/Healing
‡ Healing is the body response to injury so that normal structure and function are restored ‡ Resolution ± romoval of debris with inflammatory response ‡ Regeneration ±proliferation of parenchymal cells such that complete restoration of original tissues occurs Repair by scar [organization] when there is tissue loss - healing by proliferation of connective tissue resulting in fibrosis and scar formation At times both occur together

Injury
Cellular and vascular response

Stimulus removed (acute injury)
Parenchymal cell death (intact tissue framework) Superficial wounds Some inflammatory processes REGENERATION
(Restitution of normal structure)

Persistent tissue damage

Parenchymal cell death (damaged tissue framework) Deep wounds

HEALING
Scar formation Organisation of exudate

FIBROSIS
(Tissue scar)

Examples Liver regeneration after partial Hepatectomy Superficial skin wounds Resorption of exudate in lobar pneumonia

Examples Deep excisional wounds Myocardium infarction

Examples Chronic inflammatory diseases (cirrhosis, chronic pancreatitis, Pulmonary fibrosis)

Tissue Repair Mechanisms Cell Renewal Whether regeneration or fibrosis is dependent upon the regenerative ability of the cells/organ involved. ‡ Capability of cells to replicate Tissue Type - Labile - Stable - Permanent

Tissue Repair Mechanisms Cell Renewal
Whether regeneration or fibrosis is dependent upon the regenerative ability of the cells/organ involved. ‡ Ability to replace complex structures such as renal glomeruli Stem cells pool in labile and stable population Minority population located epidermis - basal layer adjacent to BM intestine - bottom of crypts

Labile Cells
Continuously dividing Regenerate from a population of stem cells after injury >1.5% cells in mitoses Examples - Cells in contact with environment-epidermis, alimentary tract, respiratory tract, urinary tract, vagina, cervix, uterus - Lymphoid Cells lymph node, spleen - Haematopoietic Cells

Stable Cells
Low level of replication - < 1.5% of normal adult cells are in mitoses Can respond to stimuli Examples 1. organs- liver, kidney, pancreas, adrenals, thyroid Need intact basement membrane eg. renal tubules can regenerate- Glomeruli do not regenerate 2. vascular endothelium 3. bone 4. cartilage cells 5. Mesenchymal cells Smooth muscle cells Fibroblasts

Permanent Cells
Cells don t divide No regenerative ability 0.0% cells are in mitoses Examples Neurons Lens epithelium Cardiac myocytes Skeletal muscle cells

Complete Restitution
Loss of labile population eg. skin abrasion Cells at margin proliferate to cover defect Spread as a thin sheet till defect covered When form confluent layer contact inhibition Epidermis then rebuilt from base upwards Ability of adnexal glands to regenerate - used in plastic surgery

Stimulus removed (acute injury)

Parenchymal cell death (intact tissue framework) Superficial wounds Some inflammatory processes
REGENERATION (Restitution of normal structure) Examples Liver regeneration after partial Hepatectomy Superficial skin wounds Resorption of exudate in lobar pneumonia

Parenchymal cell death (damaged tissue framework) Deep wounds

HEALING Scar formation Organisation of exudate Examples Deep excisional wounds Myocardium infarction

Wound Healing -organisation
Two Processes 1.-Granulation tissue formation with removal of dead tissue by phagocytosis 2.-Contraction of wound Cells involved organ injured - mesenchymal cells - connective tissue stem cells - fibrocytes - histiocytes - endothelial cells - macrophages,

Formation of Granulation tissue
‡ Phase of inflammation ‡ Phase of clearance ‡ Ingrowth of granulation tissue - Angiogenesis (neovascularisation) comprises of loops of capillaries supported by myofibroblasts. -Actively contracts to reduce wound size which may result in a stricture later Fibrogenesis

GRANULATION TISSUE
‡ The term granulation tissue derives from its pink, soft, granular appearance on the surface of wounds. ‡ Proliferation of new small blood vessels and fibroblasts are its characteristic histological features.

Angiogenesis

‡ Proteolysis of ECM ‡ Migration and chemotaxis ‡ Proliferation ‡ Lumen formation , maturation and inhibition of growth ‡ Increased permeability through gaps and transcytosis

‡ 1. Angiogenesis ‡ 2. Migration and proliferation of fibroblasts ‡ 3. Deposition of Extra Cellular Matrix ‡ 4. Maturation and reorganization - Granulation bed contracts as it matures - Myofibroblasts (actomyosin) act as contractile cells

Repair by fibrosis

Wound contraction and scarring
Reduce volume of repair tissue Begins in 2-3 days and completes by 14th day Result of contraction of myofibroblasts in granulation tissue. Retracts as a whole and brings together surrounding tissue. Collagen secreted at same time forms a local scar tho useful can produce defects
Stenosis/stricture intestine Permanent contractions burns

Factors favoring Fibrosis over regeneration
‡ Severe and prolonged tissue injury ‡ Loss of tissue framework (basement membranes) ‡ Large amounts of exudate ‡ Lack of renewable cell populations ‡ Consequences ‡ Loss of functional parenchymal tissue ‡ Skin with scar is more prone to tearing

Organisation
Process by which specialised tissues repaired by formation of mature fibrovascular connective tissue Granulation tissue early Dead tissue removed by macrophage Granulation tissue contracts scar forms which then undergoes remodelling eg. -Infarct

MI 18-24 hr loss of nucleus, contaction bands, coagulative necrosis

MI 3-4 day ± Hemorrhage, inflammation.

MI 1-2w ² Granulation tissue

MI 2-4 W - Resorption, fibrosis

MI >4-6 W - Collagen Scar

Infarct kidney ² healing by fibrosis

Stimulus removed (acute injury)

Parenchymal cell death (intact tissue framework) Superficial wounds Some inflammatory processes
REGENERATION (Restitution of normal structure) Examples Liver regeneration after partial Hepatectomy Superficial skin wounds Resorption of exudate in lobar pneumonia

Parenchymal cell death (damaged tissue framework) Deep wounds

HEALING Scar formation Organisation of exudate Examples Deep excisional wounds Myocardium infarction

Wound Healing - SKIN
‡ Classic example of regeneration and repair ‡ Healing by first intention (minimal necrosis & inflammation) ± primary union - clean - not infected - surgically incised - little loss of tissue - tissue elements close to one another ‡ Healing by second intention ±secondary union (extensive necrosis & inflammation)

Healing by First Intention
Example: surgical wound Result: healing with like tissue and little scar formation (fibrosis) Epithelial regeneration predominates over fibrosis 24 hours - Neutrophils migrate into fibrin clot - Basal cells at edges - Increase mitotic activity

Healing by First Intention Wound healing
24 48 hours Epithelial cells migrate and proliferate - Deposition of basement membrane Days 3 - 7 - Macrophages replace neutrophils - Neovascularization - Granulation tissue - More collagen bundles - Bridging of wound - Epithelial cells continue to proliferate

Healing by First Intention Wound Healing
Week 2 ( day 14) Collagen accumulation continues to increase - Fibroblast proliferation - WBC and edema decreases - Vascular channels regress - Blanching 4 weeks - scar formed by fibroblasts and collagen - Few inflammatory cells - Tensile strength increases

Healing by Second Intention Wound Healing
Injury more extensive tissue loss excessive - More inflammation - More fibrin - More granulation tissue - More complex repair process - wound contracts

Healing by second intention
Response characterised by - phagocytosis to remove debris - granulation tissue to fill defect - repair specialised tissue loss - epithelial regeneration to cover gap Time scale will depend on volume of defect Final cosmetic result will depend on quantum of tissue loss and scarring

Complications of wound healing
‡ ‡ ‡ ‡ ‡ ‡ ‡ Infection Implantation(epidermal inclusion ) cyst Pigmentation Weak scar Incisional hernia Keloid formation Contractures

Factors which might impair wound Repair
Systemic ‡ Age-very young and old ‡ Disorders of nutrition ‡ Vitamin C deficiency (collagen) ‡ Glucocorticoids (immunosuppression +interfere with formation of granulation tissue and wound contraction) ‡ Diabetes/immunosuppression (increase susceptibility to low virulence organisms) Local ‡ infection ‡ Poor blood supply ‡ Foreign bodies ‡ Type and volume of tissue injured ‡ Location of the injury - movement

Bone
Repair process same, slightly modified Haemorrhage hematoma facilities repair ground for cells to grow Removal of necrotic tissue Organisation of hematoma Special capillaries accompanied by fibroblasts and osteoblasts lay down irregular woven bone (callus) - replaced by lamellar bone gradually remodelled according to direction of mechanical stress.

Liver
Hepatocytes excellent regenerative capacity Hepatic architecture poor reconstruction if excessively damaged eg. Cirrhosis Combination - Parenchymal regeneration - Scar formation Outcome depends - Insult - Location - Extent - Chronicity

Kidney
Epithelium regenerates Architecture cannot regenerate - tubular damage can regenerate - glomerular damage permanent loss of filtration capacity - interstitial damage fibrosis

Muscle

Cardiac and smooth muscle permanent population- replaced by scar tissue Voluntary (skeletal) muscle limited capacity for regeneration from satellite cells, depends if muscle sheath intact

Neural tissue
Neurons - permanent cells central nervous system does not repair effectively NO FIBROBLAST proliferation in brain damage Necrotic tissue liquefactive necrosis Glial cells - may proliferate in response to injury to produce a glial scar or gliosis. Peripheral nerve damage - shows degeneration distal to trauma and recovery depends on alignment and continuity

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