Wound Healing Lecture Notes PDF

Wound Healing Dr Sarojini Devi MB52 Blk1 Learning Outcomes 1. Describe labile cells, stable and permanent cells in relation to their role in regeneration and wound healing. (C2) 2. Describe the formation of granulation tissue. (C2) 3. Describe the following: (C2) a. Healing by first intention (skin)...

Wound Healing Dr Sarojini Devi MB52 Blk1 Learning Outcomes 1. Describe labile cells, stable and permanent cells in relation to their role in regeneration and wound healing. (C2) 2. Describe the formation of granulation tissue. (C2) 3. Describe the following: (C2) a. Healing by first intention (skin) b. Healing by second intention (skin) c. Wound organization, contraction and scarring 4. Compare healing by first and second intention with the help of a suitable diagram. (C4) 5. Explain the factors which modify (influence) healing and repair. (C2) 6. Describe complications of wound healing including keloid and proud flesh. (C2) Manipal University College Malaysia 2 Types of cells based of regenerative capacity 1. Labile cells – continue to multiple throughout life under normal physiologic conditions Surface epithelial cells of epidermis, alimentary tract, respiratory tract, haemopoietic cells in bone marrow, etc. 2. Stable cells – decrease or lose ability to proliferate after adolescence but retain capacity to multiply in response to stimuli throughout adult life Parenchymal cells of organs like liver, pancreas; mesenchymal cells like endothelial cells, fibroblasts and smooth muscle cells 3. Permanent cells – lose their ability to proliferate around time of birth Neurons, cardiac muscle cells, skeletal muscles Manipal University College Malaysia 3 Relationship of parenchymal cells with cell cycle Labile cells which are continuously dividing cells remain in the cell cycle from one mitosis to the next. Stable cells are in the resting phase (G0) but can be stimulated to enter the cell cycle. Permanent cells are non-dividing cells which have left the cell cycle and die after injury. Manipal University College Malaysia 4 Manipal University College Malaysia 5 Repair Repair occur by means of 2 processes: 1. Regeneration – restores with normal cells Complete restitution of lost tissue components by identical to those injured or lost Arise from maturation of stem cells 2. Scarring – restores by deposition of connective tissue In injured tissue incapable of regeneration or tissue severely damaged Manipal University College Malaysia 6 Healing Process of healing consists of 2 events: 1. Formation of granulation tissue 2. Wound contraction and scar formation Manipal University College Malaysia 7 Granulation tissue Hallmark of wound healing It consists of a triad: i. Proliferation new blood vessels (neovascularisation) ii. Proliferation of fibroblasts and collagen iii. Non-specific inflammation Manipal University College Malaysia 8 Manipal University College Malaysia 9 Granulation tissue: numerous blood vessels, oedema and inflammatory cells Manipal University College Malaysia Trichrome stain of mature scar, showing dense collagen, with only scattered vascular channels 10 Wound contraction and scar formation Replacement of granulation tissue is known as tissue remodeling Myofibroblasts contract – cause wound contraction; collagen is deposited to form scar tissue Collagen degradation (important in tissue remodeling) brought about by matrix metalloproteinase (MMP) Zinc is an important cofactor for MMP Manipal University College Malaysia 11 Healing of skin wound (cutaneous wound healing) Based on the nature and size of the wound, can be either: 1. Healing by first intention 2. Healing by second intention Manipal University College Malaysia 12 Healing by first intention When the injury involves only epithelial layer Principle mechanism of repair by epithelial regeneration Called primary inion or healing by first intention Examples include: Clean, uninfected surgical incision approximated by surgical sutures. Clean cut with closely approximated edges Manipal University College Malaysia 13 Changes seen in cutaneous wound healing Within 24 hours: Neutrophils appear at site – release proteolytic enzymes to clear debris Within 24 -48 hours: Epithelial cells from both edges begin to migrate and proliferate along the dermis Cells meet at midline beneath the surface scab Manipal University College Malaysia 14 Day 3 Neutrophils are replaced by macrophages Key cellular constituent of tissue repair – clear extracellular debris, fibrin and foreign material Promote angiogenesis and ECN{M deposition Granulation tissue formation from the edge towards centre of lesion Manipal University College Malaysia 15 Day 5 Neovascularization reaches peak with maximum granulation tissue formation Migration of fibroblasts to the site of injury due to chemokines, TNF, PDGF, TGF-β and FGF Manipal University College Malaysia 16 Second week Continued collagen accumulation and fibroblast proliferation Diminished leucocyte infiltration, oedema and vascularity Blanching begins by increased collagen deposition with the incisional scar and regression of vascular channels Manipal University College Malaysia 17 End of first month Scar comprises acellular connective tissue devoid of inflammatory cells Covered by normal epidermis Dermal appendages in the line of incision are permanently lost Manipal University College Malaysia 18 Healing by second intention When the injury involves extensive cell or tissue loss Example: large wounds, abscesses, ulcerations, and infarcted area in parenchymal organs Process involves combination of regeneration and scarring Process is also called secondary union Manipal University College Malaysia 19 Difference between primary and secondary healing Large tissue defect – fibrin clot is larger, more intense inflammatory changes Hence large amount of granulation tissue formed At the end of 1st month – forms scar tissue made up of acellular connective tissue Wound contraction over large area – results in formation of irregular scar tissue Manipal University College Malaysia 20 Wound healing and scar tissue formation Manipal University College Malaysia (MUCM) 21 Sequence of events in wound healing Manipal University College Malaysia (MUCM) 22 Factors influencing wound healing 1. 2. 3. 4. 5. Infection – most important cause in delayed healing Diabetes mellitus – compromise tissue repair Nutritional status – protein and vit.C deficiency – inhibit collagen synthesis Glucocorticoids – have an anti-inflammatory effect Mechanical factors – increased pressure or torsion – cause wounds to pull apart or dehisce 6. Poor perfusion – atherosclerosis, DM, varicose veins 7. Foreign bodies – fragments of debris 8. Type and extent of tissue injury 9. Location of injury – over joints – hinder healing due to movement 10. Age of patient – better healing in younger age then in elderly Manipal University College Malaysia 23 Complications of wound healing 1. Infection – wound acts as portal of entry to organisms Delayed healing, increased tissue destruction, increased fibrous tissue 2. Wound dehiscence E.g. Burst abdomen after laparotomy Due to local factors (chronic cough, vomiting), hypoproteinemia, vit.C deficiency, poor nutrition 3. Ulceration – causes a local defect or excavation of the surface area 4. Hypertrophic scar and keloid formation Due to excessive collagen – forms a raised scar – hypertrophic scar If scar grows beyond the boundary of original wound and does not regress – keloid formation Manipal University College Malaysia 24 Complications of wound healing 5. Proud flesh – due to exuberant granulation tissue 6. Desmoids or excessive fibromatoses – due to exuberant proliferation of fibroblasts and connective tissue 7. Contractures – deformities of wound and surrounding tissues (common after burn injury) Manipal University College Malaysia 25 Examples of complication of wound healing Proud Flesh Desmoids Keloid Contracture scars Manipal University College Malaysia 26 References 1. 2. Robbins and Cotran Pathologic Basis of Disease 10th edition Underwood’s Pathology: A clinical approach 7th edition Manipal University College Malaysia 27 Manipal University College Malaysia 28