BMDT 6115 Wound Healing Lecture PDF

BMDT 6115: BASIC MECHANISMS OF DISEASE AND THERAPEUTICS PATHOLOGY LECTURE # PAL6 WOUND HEALING AND REPAIR DR. AYE MYAT MON Learning outcomes At the end of this session the student would be able to ▪ Classify the cells according to their regenerating capacity ▪ D...

BMDT 6115: BASIC MECHANISMS OF DISEASE AND THERAPEUTICS PATHOLOGY LECTURE # PAL6 WOUND HEALING AND REPAIR DR. AYE MYAT MON Learning outcomes At the end of this session the student would be able to ▪ Classify the cells according to their regenerating capacity ▪ Describe wound healing and its types ▪ Outline mechanisms of wound healing ▪ Discuss factors affecting wound healing ▪ List complications of wound healing  Types of cell based on their regenerative capacity 1.LABILE CELLS (continuously dividing tissues cells / proliferate throughout life) ✓ replace the destroyed cells continuously ❑ surface epithelium such as stratified squamous epithelium of the skin, oral cavity & vagina ❑ columnar epithelium of GIT, Uterus, Fallopian tubes ❑ splenic, lymphoid & haemopoietic cells 3 2. STABLE CELLS ✓ low level of replication ✓ capable of reconstituting tissue of origin ✓ basement membrane is necessary for organized regeneration ❑ Parenchymal cells of liver, kidneys, and pancreas ❑ Mesenchymal cells such as fibroblasts and smooth muscle; vascular endothelial cells 3.NON-dividing (Permanent cells) ✓ not undergo mitotic division in post-natal life ❑ nerve cells ❑ skeletal and cardiac muscle cells 4 ▪ Regeneration refers to the proliferation of cells and tissues to replace the lost structures. ▪ Repair of damaged tissues occurs by two processes, regeneration and healing. ▪ Healing restore original structures but involves collagen deposition and scar formation. 5 REPAIR BY CONNECTIVE TISSUE - GRANULATION TISSUE ✓ After injury, fibroblasts & vascular endothelial cells proliferate to form (by 3-5 days) - the specialized type of tissue - GRANULATION TISSUE (Hallmark of healing) ✓ Gross → pink, soft granular appearance on surface of wound ✓ Histology → composed of proliferation of fibroblasts, small blood vessels & mononuclear cells 6 ✓ ANGIOGENESIS OR NEOVASCULARIZATION – The process of new blood vessels development by budding or sprouting of pre-existing vessels ✓ These new vessels have leaky inter-endothelial junctions. ✓ Therefore newly formed granulation tissue is oedematous. ✓ Inflammatory cells are also seen. Angiogenesis from preexisting vessels 7 Gross picture of granulation tissue Microscopic picture Trichrome stain 8 Repair by connective tissue deposition includes the following basic features: ▪ Haemostasis ▪ Inflammation (to remove dead and damaged tissue) ▪ Angiogenesis & formation of granulation tissue ▪ Migration and proliferation of fibroblasts ▪ Wound contraction ▪ Tissue remodeling ▪ Increase in wound strength (scar = fibrosis) 9  WOUND HEALING A process by which lost or destroyed cells are replaced by viable cells after injury. PRIMARY UNION (healing by first intention) SECONDARY UNION (healing by second intention) 11 12 1. PRIMARY UNION (healing by first intention) can be seen in healing of ✓ Clean surgical incision ✓ Healing occurs without bacterial contamination & minimal loss of tissue Incision space is narrow & immediately filled with clotted blood Dehydration of surface clot → scab that covers the wound 13 ✓ Within 24 Hours Neutrophils appear at the margin of incision Proliferation of epidermis at the cut edges ✓ Within 24 – 48 Hours Spurs of epithelial cells from edges, grow along cut margins of dermis to fuse in midline beneath the scab, producing continuous thin epithelial layer. ✓ By Day 3 Neutrophils are replaced by macrophage Granulation tissue appears Collagen fibers - present in margins of incision, vertically oriented & do not bridge incision. Epithelial cells - continue proliferation 14 Primary healing 15 ✓ By day 5 Collagen bridges the incision Epidermis becomes thickened and recovers normal thickness ✓ By 2nd week Continued proliferation of collagen & fibroblasts Leukocytes & edema disappears ✓ By the end of 1st month Scar (acellular connective tissue, devoid of inflammatory infiltrate, covered by intact epidermis) Dermal appendages that have been destroyed in the line of incision permanently lost. ✓ A Year : Scar → acellular, avascular, pale collagenous scar 17 Primary healing 18 2. SECONDARY UNION (healing by second intention) ✓ Can be seen in healing of infarction inflammatory ulceration abscess surface wound with large defects ✓The common denominator is a large tissue defect that must be filled. ✓Regeneration of parenchymal cells cannot completely reconstitute the original architecture ✓Abundant granulation tissue grows to complete the repair 19 SECONDARY HEALING DIFFERS FROM PRIMARY HEALING IN: 1. Loss of greater amount of tissue 2. Greater loss of skin appendages 3. More intense inflammation 4. Production of greater amount of inflammatory exudate & necrotic debris 5. Formation of larger amount of granulation tissue 6. Contraction of surface wound 7. Production of large amount of scar 8. Slower completion of entire healing process ▪ Contracted wound results in rapid healing since lesser surface area of the injured tissue has to be replaced 20 Secondary healing 21 Primary healing Vs Secondary healing 22 23  Complications of Wound Healing 1. Infection 2. Wound Dehiscence & ulceration ✓ Due to inadequate formation of granulation tissue ✓ Burst opening of wound due to increased mechanical stress (vomiting, cough), most common with abdominal operations 3. Hypertrophic scar ✓Accumulation of excessive collagen → raised scar 4. Keloid formation ✓ if the scar grows beyond the boundaries of the original wound and does not regress, it is called a keloid 24 Hypertrophic scar Keloid Keloid Microscopic examination of keloid 25  Complications of Wound Healing 5.Proud Flesh ✓ caused by excessive granulation tissue 6. Contracture ✓ due to reduction of scar size in severe skin burns “Proud flesh". 26 Wound dehiscence Contracture 27  Factors Influencing Inflammatory Repair Rate I. Systemic Factors: 1. Age ✓ Healing in old age is slower than young 2. Immunity ✓ Immunosuppression → impairs the wound healing (WH) 3. Nutrition: ✓ Protein deficiency – reduces formation of granulation tissue & collagen ✓ Vitamin C deficiency – reduces collagen synthesis ✓ Zinc deficiency – enzymes are zinc dependent → delayed WH 28 4. Hematological derangements: Neutropenia, Hemophilia → delays repair 5. Diabetes mellitus:  blood glucose → prone to infection → delays repair 6. Hormones: Corticosteroids → impair inflammatory response → delay WH 7. Temperature: Healing slows in cold weather Rate of wound healing is directly proportional to T° of environment 29 II. Local Factors: 1. Infection → delayed wound healing 2. Types of injured tissue ✓ If injury occurs in labile cells & stable cells, repair process is rapid. In permanent cells → Scarring 30 3. Type, size, location of wound ✓ Type- A clean aseptic wound heals faster than an infected wound ✓ Size- Small wound heals faster than larger ones ✓ Location- Highly vascularized area heals faster ✓ Adhesion to bony surface – When the wound adhere to bony surface prevent wound contraction → delay repair. 4. Foreign bodies → delay repair. 5. Movements → delay healing. 6. Exposure to UV light → promotes healing 31 7. Exposure to ionizing radiation → delays healing 8. Proper coaptation of wound margin → speeds healing of incision 9. Direction of wound → Skin wound made a direction parallel to lines of Langer heals faster (due to orientation of collagen bundles in dermis) Langer's Lines 32  REFERENCES ▪ Vinay Kumar, Abul Abbas, Jon Aster, Andrea T. and Abhijit Das. Robbins & Kumar Basic Pathology, 11th Edition. Elsevier, 2023 ISBN: 978-0-323-79019-2 ▪ Vinay Kumar, Abul K. Abbas and Jon C. Aster. Robbins & Cotran Pathologic Basis of Disease, 10th Edition. Elsevier, 2021 ISBN: 978-0-323-53113-9 ▪ James C.E. Underwood, Simon S Cross. Underwood's Pathology: A Clinical Approach. 7th Edition., Elsevier,2018 13-Feb-25 33 THANK YOU