Wound Healing 2 PDF

WOUND HEALING 2 Daniela Pereira Learning objectives 1) Understand cellular response during wound healing. 2) Identify haemostasis, inflammation, proliferation/angiogenesis and matrix remodelling. 3) Discuss different types of inflammation. 4) Describe the steps involved...

WOUND HEALING 2 Daniela Pereira Learning objectives 1) Understand cellular response during wound healing. 2) Identify haemostasis, inflammation, proliferation/angiogenesis and matrix remodelling. 3) Discuss different types of inflammation. 4) Describe the steps involved in cellular response during wound healing. 1. CELL INJURY AND CELL DEATH 2. CELLULAR RESPONSE DURING WOUND HEALING 3. HAEMOSTASIS 4. INFLAMMATION 5. PROLIFERATION/ ANGIOGENESIS 6. MATRIX REMODELLING 7. TISSUE REPAIR 8. FACTORS IMPAIRING HEALING AND REPAIR 9. TYPES OF TISSUE HEALING 3. HAEMOSTASIS HAEMOSTASI S  First stage of wound healing  Stops bleeding after vascular damage  Three main steps:  Vasoconstriction  Primary haemostasis  Secondary haemostasis 4. INFLAMMATION “Without inflammation, infections would go unchecked, and wounds would never heal.” INFLAMMA TION  Inflammation is the primary defence against pathogenic wound invasion.  It is a response of vascularised tissues to infections and tissue damage that brings the necessary cells and molecules from circulation to the affected area.  The morphologic hallmarks of acute inflammatory reactions are the dilation of small blood vessels and the accumulation of leukocytes and fluid in the extravascular tissue. Increase blood flow and vascular permeability PAIN Oedema, redness, warmth and swelling INFLAMMATORY REACTION 1 Steps of inflammation (5 R’s): Recognition of the injurious agent (1); 2 Recruitment of the leucocytes (2); Removal of the agent (3); Regulation (control) of the response (4); Resolution (repair) (5). 3 4 5 ACUTE INFLAMMATION ACUTE INFLAMMATION INFLAMMATION Serous Fibrinous inflammation inflammation Fig 1- Fig 2 - Purulent inflammation Fig 3- CHRONIC INFLAMMATION C D The morphology of an ulcer. (A) A chronic duodenal ulcer. (B) Low-power cross-section view of a duodenal ulcer crater with an acute inflammatory exudate in the base. (C) Chronic inflammation in the lung, showing all three characteristic histologic features: (1) collection of chronic inflammatory cells (*), (2) destruction of parenchyma (normal alveoli are replaced by spaces lined by cuboidal epithelium, arrowheads), and (3) replacement by connective tissue (fibrosis, arrows). (D) In contrast, in acute inflammation of the lung (acute bronchopneumonia), neutrophils fill the alveolar spaces and blood vessels are congested. 5. PROLIFERATION AND ANGIOGENESIS PROLIFERA TION  As the inflammatory phase ends, angiogenesis occurs.  Angiogenesis involves endothelial cell proliferation, migration, and branching to form new blood vessels.  Concurrent with proliferation of endothelial cells, pericytes within the basal lamina are activated which scaffold and provide structural integrity to the endothelial cells. PROLIFERATION AND ANGIOGENESIS 5. PROLIFERATION Platelets within the plug AND ANGIOGENESIS and leucocytes release growth factors and cytokines which are important cellular mediators for the subsequent phases of healing. Fibroblasts Growth Factor (FGF) Transforming Growth Factor beta (TGF-β) Platelet-derived Growth Factor (PDGF) Vascular endothelial growth factor (VEGF) Keratinocyte growth factor (KGF) Insulin Growth factor (IGF) ANGIOGENESIS ANGIOGENESIS  Angiogenesis is the process of new blood vessel development from existing vessels.  It is critical in healing at sites of injury, in the development of collateral circulations at sites of ischemia, and in allowing tumours to increase in size beyond the constraints of their original blood supply.  This process involves a variety of growth factors, cell-cell interactions, interactions with ECM proteins and tissue enzymes.  6. MATRIX REMODELLING REMODEL LING  Remodelling of the extracellular matrix (ECM) occurs throughout the injury response, starting with the deposition of a fibrin clot and ending years later with the formation of a mature, type I collagen-rich scar.  Fibroblasts are the major cell type responsible for wound ECM remodelling, replacing the initial fibrin clot with hyaluronan, fibronectin and proteoglycans, and forming mature collagen fibrils later in repair. 6. MATRIX REMODELLING The composition of collagen in uninjured adult skin is about 80% type I collagen and 10% type III collagen. The granulation tissue is predominantly composed of collagen type III (approx. 30%), with only 10% collagen type I. Collagen type III is replaced by collagen type I during healing, which increases the tensile strength of the forming scar. The integrity and architecture of scar ECM never fully return to that of unwounded skin. Summary  Cellular response during wound healing involves four steps: haemostasis, inflammation, proliferation and angiogenesis, and matrix remodelling.  Haemostasis is the first phase of wound healing and involves 3 main steps: vasoconstriction, primary haemostasis and secondary haemostasis.  The inflammation is a critical defence mechanism marked by increased blood flow, redness, warmth, and pain. It involves the recruitment of leukocytes and the removal of the injurious agent, followed by regulation and resolution of the response.  Proliferation and Angiogenesis involve the formation of new blood vessels and the activation of cells necessary for wound closure and tissue repair. Growth factors like VEGF and TGF-β play a significant role.  Matrix Remodelling is the final phase, where the extracellular matrix is remodelled, leading to the formation of scar tissue.