Healing: Regeneration And Repair Flashcards
What processes are involved in wound healing?
- Haemostasis -vessels are open
- Inflammation - due to tissue injury
- Regeneration (resolution, restitution) and/or repair (organisation)
What is regeneration? (After wounds)
Restitution with no or minimal evidence that there was a previous injury
Eg
-healing by primary intention
-superficial abrasion
What is the difference between an abrasion and an ulcer?
Abrasions: Epidermis and dermis effected- easily healed by regeneration
Ulcer: injury into submucosa below the level of mucosa
Which cells replicate in regeneration?
Mainly derived from stem cells (many terminally differentiated cells cant divide)
What type of replication do stem cells show?
Asymmetric replication
One stays as stem cell, other daughter cell differentiates into mature cell
Whereabouts in the tissues are the stem cells:
- Epidermis
- intestinal mucosa
- Liver
- Basal layer (adj to basement membrane)
- Bottom of crypts
- Between hepatocytes and bile ducts
What are the 3 types of stem cells?
- Unipotent - most adult stem cells, only produce one type of cell
- Multipotent - produce several types of differentiated cell eg haematopoietic stem cells
- Totipotent - embryonic stem cells, can produce any type of cell and therefore any tissue of the body
Not all tissues can regenerate, what are the two types that can and the one type that cant? Describe the types and give examples
Can:
1. Labile: short lived cells that are replaced from cells derived from stem cells. Eg surface epithelia, haemotopoietic tissues
- Stable: normally low level or replication but are capable of rapid proliferation, both stem cells and mature cells proliferate. Eg bone, fibrous tissue, endothelium
Cant:
1. Permanent: mature cells cant undergo mitosis and no or only few stem cells present. Eg neural tissues, skeletal muscle, cardiac muscle
- in permanent tissue there isn’t enough or any stem cells to repair the wound so there is scaring instead of regeneration
What stage of the cell cycle are the 3 types of tissue in?
Stable
Labile
Permanent
Stable- G0 - can enter cell cycle if needed
Labile- continually going round cell cycle
Permanent- not even in G0, they’re not part of the cycle
In order for regeneration to occur in labile or stable tissue what must be intact?
A connective tissue scaffold
What is fibrous repair?
Healing with formation of fibrous connective tissue = scar
- specialise tissue is lost
- healing by secondary intention
When does fibrous repair occur?
When there is Significant tissue loss
And/or if permanent or complex tissue is injured
What is the time line for scar formation?
Sec-min: haemostasis Min-hr: acute inflammation 1-2 days: chronic inflammation 3 days: granulation tissue forms 7-10 days: early scar (when stitched are taken out) Weeks-2 years: scar maturation
What is granulation tissue and when does it occur in the formation of a scar?
Collection of developing capillaries, fibroblasts myofibroblasts and chronic inflammatory cells. Has a granular appearance and texture
3 days
What is the function of granulation tissue in the process of fibrous repair? (3)
Fills the gap
Capillaries supply oxygen, nutrients and cells
Contracts and closes the hole
Describe the process of fibrous repair (6)
- blood clots
- Neutrophils infiltrate and digest clot
- Macrophages and lymphocytes are recruited
- Vessels sprout, myofibroblasts and fibroblasts make glycoproteins
- Vascular network, collagen synthesised, macrophages reduced
- Maturity, cells much reduced, collagen mature, contracts and remodels
What cells are involved in fibrous repair?
Inflammatory cells
Endothelial cells
Fibroblasts and myofibroblasts
What is the role of inflammatory cells in fibrous repair?
- phagocytosis of debris- neutrophils and macrophages
- production of chemical mediators-lymphocytes and macrophages
What is the role of endothelial cells in fibrous repair?
Proliferation leading to angiogenesis
What is the role of fibroblasts and myofibroblasts in fibrous repair?
- produce extracellular matrix proteins eg collagen
- responsible for wound contraction (contraction of fibrils within myofibroblasts)
Why are old scars white?
Because there is no regeneration of melanocytes
Why do scars stretch as they age?
Because fibroblasts cant lay down elastin
What is intracrine signalling?
When a cell produces signalling molecules that work within the cell on receptors.
Similar to autocrine accepted the signalling molecule never leaves the cell
How are skin grafts taken so not to destroy the donor site?
You can spilt the skin at a very superficial level leaving the sweat glands and hair follicles intact, meaning the cells will grow up and healing of the donor site will be good.
How does bone heal?
- Haematoma: fills gaps and surrounds injury
- Granulation tissue forms: cytokines activate osteoprogenitor cells
- Soft callus: 1 week, fibrous tissue and cartilage within which woven bone forms (poorly organised)
- Hard callus: several weeks, woven bone
- Lamellar bone: relaxes woven bone, remodelling to direction of mechanical stress. Bone not stressed is reabsorbed and outline is re-established
What local things can influence wound healing?
Local factors
- Type, size, location of wound
- Mechanical stress
- Blood supply
- Local infection
- Foreign bodies (surgeons use very smooth thread so that foreign bodies cannot grow on it)
What general factors can influence wound healing?
- Age
- Anaemia, hypoxia and hypovolaemia
- Obesity
- Diabetes
- Genetic disorders
- Drugs
- Vitamin deficiency
- Malnutrition
(7/8 do you have the proteins and minerals needed)
What are the complications of fibrous repair?
- insufficient fibrosis
- formation of adhesions
- loss of function
- disruption of complex tissue relationships within an organ
- overproduction of fibrous scar tissue
- excessive scar contraction
How is insufficient fibrosis an issue of fibrous repair?
Can lead to: Wound dehiscence/ hernia/ ulceration
Can happen in someone with obesity/elderly/malnutrition/steroids
There is not enough scaring and the wound opens
How is formation of adhesions a complication of fibrous repair?
An adhesion is an area of fibrotic tissue that is formed between structures and organs, it can block tubes, wrap around tubes and compromise organs
Eg intestinal obstruction following abdominal surgery
How is loss of function a complication of fibrous repair?
Lots of fibrosis can replace the tissues of an organ and that impacts on the function of the organ
Eg healed myocardial infarction with non-contracting area of myocardium
How is ‘disruption of complex tissue relationships within an organ’ a complication of fibrous repair?
If there is distortion of architecture interfering with normal function of organs
Eg liver cirrhosis
How is overproduction of fibrous scar tissue a complication of fibrous repair?
You can get keloid scars (big purple/pink scars bulging) as a result of collagen in Dermis
How is excessive scar contraction a complication of wound repair?
Can cause obstruction of tubes, disfiguring scars can occur following burns or joint contracture-the skin doesn’t grow with the limb (fixed flexures)
When might you get oesophageal strictures?
When acid reflux causes injury there is contraction during repair=stricture
