What is the Parenchyma?
Functional parts of an organ
What is the Stroma?
The structural tissue of organs
Connective tissues
What are the causes of Tissue Damage? (6)
Trauma Infection Physical and Chemical Agents Tissue Necrosis Foreign Bodies Immune Reactions
What is Diapedesis?
Passage of blood ells through intact walls of the capillaries
Typically accompanies inflammation
What events occur in the Haemostasis Phase?
Platelet Aggregation
Release of Pro-Inflammatory mediators
Diapedesis
What events occur in the proliferation phase?
Alterations in cell-cell and cell-matrix interactions
Migration
Cross-talk between MMPs, integrins and cells
Cytokine and growth factor release
ECM production
Re-epithelisation
Angiogenesis
Fibroplasia
ECM deposition
What are MMPs?
Matrix metalloproteinases
Group of enzymes responsible for the degradation of most extracellular matrix proteins
What is ECM?
Extracellular Matrix
Collection of extracellular molecules secreted by cells that provides structural and biochemical support to the surrounding cells
Regulates movement and growth of cells
What event occurs during the Remodelling phase?
Fibroblast to myofibroblast differentiation
Scar Formation
ECM remodelling and degradation
Contraction
What are the phases of tissue repair?
Haemostasis
Inflammation
Proliferation
Remodelling
What are the fundamentals of inflammation?
Rubor - Redness Calor - Heat Dolor - Pain Tumor - Swelling Functio laesa - Loss of Function
What is a fibroblast?
Type of cell that synthesises the ECM and collagen, the stroma and plays a critical role in wound healing.
Most common cells of connective tissue
What is PDGF?
Platelet derived growth factor
What is VEGF?
Vascular endothelial growth factor
Angiogenesis
What is CXCL5?
Platelet Factor 4
Binds with high affinity to heparin
Neutralises heparin like molecules on endothelium
Inhibit local antithrombin activity to promote coagulation
Strong chemoattractant for neutrophils and fibroblasts
What is CCL5?
Chemokine ligand 5
chemotactic for T cells, eosinophils and basophils
What is bFGF?
Basic Fibroblast Growth Factor
Angiogenesis
What is TGFβ?
Transforming Growth Factor Beta
Cascade causes differentiation, chemotaxis, proliferation, activation of immune cells
What is the function of platelets in tissue repair?
What stage are they involved in?
Formation of Platelet Plug
Release pro-inflammatory mediators
Haemostasis Phase
What are the stages of Leukocyte Recruitment?
Rolling
Integrin Activation by Chemokines
Stable Adhesion
Migration through Endothelium
What is the roll of neutrophils in tissue repair?
Phagocytosis
Recruited within minutes
Respiratory burst
Anti-microbial
Haemostasis/Inflammation phase
What is the respiratory burst?
In neutrophils and macrophages
Intracellular bleach (reactive oxygen species) released to kill engulfed bacteria
Green Enzymes - green discharge
What is the role of Macrophages in Tissue Repair?
Resident macrophages - alveolar macrophages and kupffer cells (liver)
Monocyte derived macrophages
M1 - inflammatory
M2 - removing debris
Phagocytic
Respiratory burst
Produce Nitric Oxide
What is Granulation Tissue?
New connective tissue and microscopic blood vessels hat form on the surfaces of a wound during the healing process.
Typically grows from the base of the wound and is able to fill wounds of any size
What does the outcome of the proliferative phase depend on?
Proliferative potential
What are Labile cells?
Where are they found?
Continually dividing
Reproduce new stem cells to replace functional cells
GI tract
Epidermis
Mucosal epithelia
Bone Marrow
What are Quiescent cells?
Where are they found?
Stem cells that retain the ability to divide
Enter the cell cycle when activated
Hepatocytes
Renal tubular epithelium
Pancreatic acini
What are permanent cells?
Where are they found?
Terminally differentiated cells
No proliferative capacity
Damage to these cells leads to scarring
Cardiac myocytes Brain cells Neurons Skeletal muscle Red blood cells
What are the different pathways for angiogenesis? (2)
Mobilisation of EPCs (endothelial progenitor cells) from bone marrow
Angiogenesis from pre-existing vessels
Driven by VEGF
What substances make up the Extracellular Matrix?
What is the role of each substance?
Collagen - tensile strength
Elastin - elastic stretch and recoil
Proteoglycans - regulate structure and permeability, moderate cell growth, bind growth factors
Adhesive glycoproteins - fibronectin and laminin - cell recognition, adhesion, migration and proliferation
Integrins - major cell surface receptors, mediating cell adhesion to ECM
What types of cels can become myofibroblasts?
Fibrocytes
Resident fibroblasts
Alveolar epithelium
What is first intention skin healing?
Focal disruption of the basement membrane and limited loss of epithelial cells
surgical incision
What is skin healing by second intention?
Larger injury than first intension
Edges can’t be Brough together, due to tissue loss
Results in large scar and contraction
What are the local factors that delay tissue repair? (7)
Poor blood supply (atherosclerosis) Denervation Infection (and biofilm formation) Foreign bodies Mechanical stress Overwhelming necrosis Size
What are the systemic factors that delay tissue repair? (9)
Anaemia Nutritional deficiencies (vitC) Systemic infection Smoking Genetic Disorders (marfans) Diabetes Malignancy Haematological abnormalities Age
How, when and where does fibrosis occur?
Excessive deposition of ECM
During abberant wound healing there is too much collagen production
Lung, liver, cardiac, skin, kidney
What are complications of skin healing? (3)
Deficient scar: dehiscence, ulceration
Excessive scar: hypertrophic, keloid, proud flesh
Contractures: permanent shortening of a muscle or joint