Tissue Repair Flashcards by Lucy Lee-Smith

What is the Parenchyma?

Functional parts of an organ

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What is the Stroma?

The structural tissue of organs

Connective tissues

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What are the causes of Tissue Damage? (6)

Trauma
Infection
Physical and Chemical Agents
Tissue Necrosis
Foreign Bodies
Immune Reactions

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What is Diapedesis?

Passage of blood ells through intact walls of the capillaries

Typically accompanies inflammation

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What events occur in the Haemostasis Phase?

Platelet Aggregation
Release of Pro-Inflammatory mediators
Diapedesis

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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

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What are MMPs?

Matrix metalloproteinases

Group of enzymes responsible for the degradation of most extracellular matrix proteins

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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

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What event occurs during the Remodelling phase?

Fibroblast to myofibroblast differentiation

Scar Formation
ECM remodelling and degradation
Contraction

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What are the phases of tissue repair?

Haemostasis
Inflammation
Proliferation
Remodelling

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What are the fundamentals of inflammation?

Rubor - Redness
Calor - Heat
Dolor - Pain
Tumor - Swelling
Functio laesa - Loss of Function

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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

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What is PDGF?

Platelet derived growth factor

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What is VEGF?

Vascular endothelial growth factor

Angiogenesis

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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

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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