Lecture 12 - Kapila - Healing & Repair Ii - 26 Sep 2006

Healing and Repair – II Outcome in different tissues Kusum Kapila September 2006

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 – primary union - clean - not infected - surgically incised - little loss of tissue - tissue elements close to one another Healing by second intention –secondary union

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

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

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

Factors- responsible VEGF – influences angiogenesis Cellular migration and proliferation by - Growth factors - PDGF - TGFB - FGF - cytokines, - integrins ,etc

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

Wound strength Immediate )due to sutures( 70% 1 week 10% increases with time to 70-80% wound strength at 3 months doesn’t get much better

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

Healing - Peritoneum Defect if sutured or contaminated with fibrin or foreign matter such as glove powder heals by angiogenesis-contact with another surface such as serosa of the intestine can result in adhesion. Defect if cleaned and left unsutured – perivascular connective tissue proliferates, debris is removed and the surface cells differentiate into new mesothelial lining cells. Healing is rapid, complete with little risk of adhesions.

Gastrointestinal tract Depends on depth of injury Mucosal erosions – loss of partial thickness, heal fast, may bleed Mucosal ulceration – loss of full thickness - mucosa replaced from margins - muscle cannot regenerate - vessels bleed, macrophages remove debris, granulation tissue at base, mucosa regenerates from margin. If cause persists ulcer – chronic – heals by fibrosis – can produce distortion.

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

Bone-Healing –causes for delay Movement - continued – fibrous union - lesser degree – excessive callus increased time for absorption Interposed soft tissue Gross misalignment Infection Pre-existing bone disease - pathologic fracture

Liver Hepatocytes excellent regenerative capacity Hepatic architecture – poor reconstruction if excessively damaged eg. cirrhosis

Healing - Liver 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

Healing - Kidney Limited regenerative capacity Cortical tubules - good Medullary tubules - Minimal Glomeruli - None Tubules need basement membrane

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 Vascular smooth muscle – differ as new vessels can be formed.

Healing - Heart Granulation tissue Scarring No regeneration

Heart – healed by fibrosis – special st

Healing - Lung Alveoli w/intact BM - Regeneration - Type II pneumonocyte Exudate - Fibrosis Alveoli w/o BM - Scarring

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 wallerian degeneration distal to trauma and recovery depends on alignment and continuity

Peripheral nerve damage Affects axons and their supporting structures – Schwann cells Transaction of a nerve causes axons to degenerate upto two nodes proximally Distally there is Wallerian degeneration followed by proliferation of Schwann cells in anticipation of axonal regrowth

Peripheral nerve damage