Wound Healing & Repair Flashcards
What is parenchyma? Give a couple of examples.
Organ specific cells related to the function e.g.
- Parenchyma of the kidney is the epithelial tissue in the renal tubes
- Parenchyma of the heart is the muscle tissue made up of cardiac muscle cells
What is stroma?
‘Background’ tissue that provides structure, mechanical and nutritional support to the organ
What are the 4 types of tissue? What are their functions?
- Epithelia: protection of organs, containment of body fluid, absorption and secretion in skin
- Connective tissue: several cell types and EC products that function in mechanical reinforcement, immune surveillance, diffusion of nutrients and wastes
- Muscle: specialised for gross movement through cellular contraction
- Nervous tissue: rapid-long distance signalling
What characterizes epithelial tissue?
Close cell apposition and presence at a free surface
What is the structure of connective tissue?
It is vascularised and cells are not in close contact but embedded in ECM, its made up of:
- Fibrous components e.g. collagen and elastin
- GAGs to support collagen
- Proteoglycans (GAGs attached to core protein)
What are the 2 types of proper connective tissue?
- Loose: contains numerous cells and loose fibre arrangement in a viscous matrix e.g. haemopoietic/lymphatic tissue
- Dense irregular: dense woven network of collagen and fibres in a viscous matrix e.g. joint capsules, tendons and ligaments
What are the 6 types of specialised connective tissue?
- Loose connective tissue under skin
- Fibrous connective tissue forming a tendon
- Adipose tissue
- Cartilage at end of bone
- Bone
- Blood
What is a wound?
Injury/trauma to tissues disrupting the function and structure of that tissue
What is healing?
The process of returning to health restoring structure and function of injured/diseased tissues
What are the stages of wound healing?
- Haemostasis (<24h): wound closed by clotting/coagulation, platelets and fibrin adhere to sit and thrombus is formed
- Inflammatory (0-4dys): platelets control bleeding, macrophages prevent infection and neutrophils induce inflammation
- Proliferative (1-14dys): angiogenesis, epithelialisation, contraction and fibrous tissue formation
- Remodelling (21dys-yrs): maturation phase where collagen is remodelled and becomes realigned but injured sites tend to be weaker than normal sites
What can happen after an acute tissue injury?
- Injury via infarction, bacterial infections, toxins and trauma
- Acute inflammation via vascular changes, neutrophil recruitment and mediators
- This can go on to:
- Resolution where injurious stimuli is cleared along with mediators and acute inflammatory cells, injured cells are replaced and normal function ensues
- Pus formation (abscess) which can heal
- Healing causes fibrosis and loss of function
- Progression to chronic inflammation
What can happen after a chronic tissue injury?
- Injury via viral infections, chronic infections, persistent injury and autoimmune diseases
- Chronic inflammation via angiogenesis, mononuclear cell infiltrate and fibrosis (scar)
- Healing in the form of fibrosis can cause loss of function
What is tissue repair (healing)?
The restoration of structure and function of damaged tissue via 2 reaction types:
- Regeneration
- Scar formation
What is regeneration?
Healing in which new growth completely restores portions of damaged tissue to their normal state as stable tissues can proliferate when stimulated - ECM plays a major role and it is driven by growth factors e.g. PDGF, VEGF and TGF-β
What are the different types of tissues in terms of their dividing potential?
- Labile: continuously proliferate in order to replace dead or sloughed-off cells e.g. skin, GI and salivary gland tissue
- Stable: cells that normally exist in non-dividing state but can enter cell cycle in response to stimuli such as cell injury e.g. parenchymal cells of liver, kidney and pancreas
- Permanent: non-dividing cells leading to scar formation e.g. cardiac and skeletal
How are growth factors produced in regeneration?
Macrophages and lymphocytes at injury site will produce them as part of inflammatory process OR parenchymal or stromal (connective tissue) cells in response to cell injury so they are produced transiently in response to external stimulus and act by binding to cellular receptors e.g. EGF, TGFα, VEGF and FGF
How do growth factors take part in regeneration?
Stimulate:
- Survival
- Proliferation of particular cells
- Migration
- Differentiation
- Entry of cells into cell cycle
What is the role of extracellular matrix (ECM) in regeneration?
It is the ever-changing background for regeneration and wound healing functioning to store and present GFs as well as acting as a scaffold to which migrating cells adhere
What is scar formation and when do it occur?
Replacement of damaged parenchymal cells with connective tissue resulting in incomplete restoration of architecture and function in severe or chronic injuries where parenchymal cells and connective tissue (scaffolding) have become damaged or in permanent non-dividing tissues e.g. cardiac and skeletal
What is angiogenesis?
Process of new blood vessel development involving sprouting of new vessels from existing ones where endothelial cells proliferate and migrate and derived by GF (e.g. VEGF) - critical in healing at sites of injury and development of collateral circulation at ischaemic sites
How does scar formation occur?
- Stimulated by GF e.g. TGFβ, PDGF and FGF
- Migration and proliferation of fibroblasts into injury site
- Deposition of ECM proteins produced by these cells
- New connective tissue together with blood vessels has pink granular appearance and is called granulation tissue
What is remodelling?
Connective tissue in the scar continues to be modified and remodelled to improve the tensile strength of the wound (70-80% of normal by 3 mths but no more) which is the outcome of the repair process where there is a balance between synthesis and degradation of collagen/ECM proteins (accomplished by MMP family)
What are 3 clinical examples of tissue repair?
- Healing of skin wound
- Healing of bone fractures
- Fibrosis in internal organs
How does the healing of a skin wound occur?
Involves both epithelial regeneration and formation of connective tissue scar illustrating general principles applying to healing in all tissues but depending on nature and size of wound it can occur by:
- 1st intention (primary union)
- 2nd intention (secondary union
What is healing by first intension?
The incision causes only focal disruption of epithelial BM continuity and death of relatively few epithelial and connective tissue cells so epithelial regeneration is the principle repair mechanism and only a small scar is formed with minimal wound contraction e.g. healing of a clean uninfected surgical incision approximated by surgical sutures
What are the steps of first intention healing?
- Narrow incisional space first fills with fibrin-clotted blood
- Within 24 hours neutrophils are present at the incision margin migrating towards the fibrin clot (acute inflammation)
- Within 24-48 hours, epithelial cells from both edges have begun to migrate and proliferate along the dermis
- At day 3-7, neutrophils have been replaced by macrophages and angiogenesis reaches its peak
- Granulation tissue gradually invades the incision space
- In week 2, there is continued collagen accumulation and fibroblast proliferation (scar maturation)
- Remodelling of scar continues for months aiming to increase wound tensile strength
What is second intention healing?
A more complex repair process involving the development of abundant granulation tissue with ECM accumulation and scar formation which is followed by wound contraction mediated by action of myofibroblasts e.g. large wounds at sites of abscess formation, ulceration and infarction
How does second intention healing vary in comparison to first intention healing?
- Larger clot/scab
- Inflammation more intense due to large tissue defects having a greater volume of necrotic debris, exudate and fibrin that must be removed
- Large defects requiring great volumes of granulation tissue to fill gaps which results in a greater mass of scar tissue
- Involves wound contraction meaning within 6 weeks large skin defects reduced to 5-10% of original size
Why is fracture healing different in cortical bone than in trabecular bone?
Because trabecular bone has a better blood supply and less necrosis
What are the 6 stages of fracture healing?
- Haematoma
- Granulation tissue
- Callus
- Woven bone
- Lamellar bone
- Remodelling
What happens in the haematoma stage of fracture healing?
Bleeding from ruptured vessels
Inflammatory reaction where phagocytes move into area
What happens in the granulation tissue stage of fracture healing?
Granulation tissue (capillary loops in loose connective tissue) replace haematoma
Cell proliferation occurs in response to GFs/cytokines
What happens in the callus stage of fracture healing?
Callus formation occurs as irregular swelling that bridges gap between bone ends - made of fibrocellular material and cartilage initially
What happens in the woven bone stage of fracture healing?
Osteoprogenitor cells proliferate and move into area forming woven bone strengthening the callus from 3 weeks
What happens in the lamellar bone stage of fracture healing?
Initial woven bone callus is gradually replaced by mature lamellar bone
What happens in the remodelling stage of fracture healing?
Osteoclasts and osteoblasts remodel the lamellar bone into an appropriate form related to function in response to stresses
Excessive callus is reabsorbed and medullary cavity re-established
What is fibrosis?
The excessive deposition of collagen and other ECM components in a tissue more referring to chronic diseases in contrast to scars even though the basic mechanisms are the same during tissue repair, which can cause organ dysfunction and failure e.g. RA pannus formation, ankylosis and pulmonary fibrosis
What are the local factors that affect tissue repair?
INFECTION Mechanical factors Poor perfusion (due to arteriosclerosis, diabetes or obstructed venous drainage due to varicose veins) Foreign bodies Size of wound Location of wound Type of wound
What are the systemic factors that affect tissue repair?
Nutritional status Metabolic status e.g. DIABETES Circulatory status Hormones Age Collagen disorders
What is clinically the most important cause of delay in healing?
Infection as it prolongs inflammation and potentially increases the local tissue injury
How does nutrition affect tissue repair?
Protein deficiency esp. vitamin C deficiency inhibit collagen synthesis and retard healing
How does mechanical variables affect tissue repair?
Increases local pressure or torsion may cause wounds to pull apart or dehisce
What are the 3 main complications of tissue repair?
- Inadequate formation
- Excessive formation
- Formation of contracture
Why might a tissue inadequately repair?
- Dehiscence/rupture: separation of surgical wound layers
- Evisceration: extrusion of viscera outside the body through surgical incision
- Ulceration: a lesion through the skin or a mucous membrane results from loss of tissue, usually inflammation
How might a tissue excessively repair?
- Keloid formation: accumulation of excessive collagen giving rise to prominent raised scars (common in Africans)
- Granulation tissue: exuberant tissue protrudes above level of surrounding skin and hinders re-epithelialization (‘Proud Flesh’)
What are contractures?
Fibrosis of connective tissue in skin, fascia, muscle or a joint capsule that prevents normal mobility of the related tissue or joint being made primarily by myofibroblasts e.g. severe burns and neurologic conditions (e.g. stroke, nerve damage)
