Healing

Question 1

Repair

Answer 1

Replace significant amounts of dead cells with scar.

Question 2

Labile cells

Answer 2

Cells which are constantly dividing- replacing dead cohorts.

Include: red and white blood cells, and epithelial cells of the epidermis of the skin.

Question 3

Stable cells

Answer 3

Virtually all internal organs are largely comprised of stable cells; liver, kidney, pancreas, lung and spleen.
Low mitosic rate- cannot replace themselves, but often replace with scar.
All connective tissues such as fibroblasts, osteoblasts etc
Two other important cells are endothelial cells and smooth muscle cells

Question 4

Permanent cells

Answer 4

Do not replicate in post- natal human.
- neurons, cardiac muscle cells, skeletal muscle cells
When these cells die, tissue deficit is eventually replaced by scar, formed by localised astrocytes (brain) or fibroblasts (cardiac and skeletal muscle)

Question 5

Skin wound healing: first phase, inflammatory phase (up to day 3)

Answer 5

Tissue damaged, vessels severed, bleeding occurs and blood clots. Blood clot is mainly comprised of the temporary fibrous protein, fibrin, as well as platelets.
Polymorphs, fibroblasts, and endothelial cells migrate into the fibrin meshwork using the fibrin as a scaffold for guidance.
Fibrin also inhibits microbes from infiltrating the wound.
Factors released from clot and injured/ dying tissue cells initiate repair, resulting in the migration of macrophages and mast cells into the clot.

Question 6

Skin wound healing: second phase, Proliferative phase (day 3 onwards)

Answer 6

Various factors released from the clot, platelets, injured and dying cells stimulate both fibroblastic and endothelial cell proliferation.

Question 7

Skin wound healing: third phase, repair and remodelling phase (day 5 onwards)

Answer 7

Endothelial cells migrate using the fibrin meshwork as a scaffold to move along and meet with other endothelial cells to form blood vessels. Termed angiogenesis or neurovascularisation.
Fibroblasts also migrate along the fibrin. Once they stop migrating, they start to form type 3 collagen, which is towards the end of the first week after wounding.
Type 3 collagen is immature, thin fibred collagen and is gradually replaced by the more mature type 1 collagen
The new tissue is granulation tissue
Wound contraction behinds (elicited by myofibroblasts) during the second week of healing in a non-apposed (non sutured or such-like) wound, along with the ongoing maturation of collagen and regeneration of the epidermis.

Question 8

Reducing wound area

Answer 8

Fibroblasts differentiate into elks called myofibroblasts. Myofibroblasts appear in non-opposed wounds at about 6-10 days after injury and produce contraction, to reduce diameter of wound, reducing amount of granulation tissue and producing tension which stimulates production of type 1 collagen over type 3.
Contraction does not occur if edges are apposed, eg by stitches. This is called primary intention wound healing- myofibroblasts do not develop here, artificial tension created. Secondary intention is per normal, but takes longer and produces more scar.

Question 9

Regeneration

Answer 9

Replacement of dead cells/ tissue with exactly the same cells that have died or are missing. Eg. Epidermis

Question 10

Endothelial cells and angiogenesis

Answer 10

Involves a phenotypic alteration of the endothelial cell, it’s migration and various mitogenic stimuli. Pseudopodia extend from endothelial cells on day 2 after wounding.
Macrophage growth factors act to induce both endothelial cells migration and cell division. Low oxygen tension also stimulates angiogenesis. Lymphatics are also regenerated in the wound and are essential to prevent oedema.
This new tissue that is formed is called granulation tissue.

Question 11

Wound tensile strength

Answer 11

Type 1 collagen contributes to tensile strength.

Type 1 collagen increases tensile strength as it is more difficult to pull the wound apart.

Question 12

Contracture

Answer 12

Late event in wound healingninnehichncollagen fibres shorten due to the remodelling of these fibres over time, which results in pulling in of the wound.

Question 13

Systemic factors that delay healing: Age

Answer 13

Decreased peripheral blood flow, decreased supply of both inflammatory cells and nutrients to the healing tissue. Reduces the clearance of metabolites, bacterial and foreign materials all of which impede healing.
Decreased wound tensile strength.
Reduced collagen formation.

Question 14

Systemic factors that affect healing: nutrition

Answer 14

Protein- collagen is fibrinous protein therefore requires intake of protein.
Zinc- required in formation of collagen, anti-inflammatory properties, lack of zinc may cause reduced healing response
Vitamin C- results in inability of collagen to aggregate into fibres. May result in formation of spontaneous wounds.

Question 15

Systemic factors that delay healing: WBC disorders

Answer 15

Any reduction in white blood cell number will result in prolonged wound healing - being old, white blood cell malignancies or problems with production

Question 16

Systemic factors which delay healing: clotting abnormalities

Answer 16

The ability to produce a fibrin clot quickly and adequately is critical for wound healing.
Fibrin provides a scaffold for cells to migrate along
Fibrin and its break down products also stimulate cell replication and migration
Therefore, wound healing will take longer to heal in individuals who have difficulty in producing an adequate fibrinous clot.

Question 17

Systemic factors which delay healing: diabetes mellitus

Answer 17

More susceptible to develop peripheral blood vessel disease than non- diabetics
Diabetes can induce decreased nutrient supply, metabolic waste clearance and reduced inflammatory response.
Higher susceptibility to infections
White blood cells have reduced response to chemotactic factors

Question 18

Systemic factors delaying healing: corticosteroids

Answer 18

Wounds take longer to heal in patients who take glucocorticosteroids as this drug suppresses inflammation.
“You need a normal inflammatory response to get a normal healing response”
Applying topical cortisone in first two weeks will also delay healing

Question 19

Local factors delaying healing:

Answer 19

Local diminution of blood supply 
Infection 
Foreign bodies 
Excessive movement 
The type of tissue injured- Labile should heal more quickly 

“You need the initial inflammatory response to stop before you get a normal healing response”

Question 20

Complications involving tissue repair: healing of myocardial Infarct

Answer 20

Most occur in left ventricular wall and are usually caused by a thrombosis blocking blood flow to portion of the heart.
After infarction, stimulated inflammatory response.
Response will trigger repair, with necrotic tissue being replaced by granulation tissue and eventually scar.
Fibroblasts and endothelial cells will divide and migrate into the fibrinous exudate from surrounding viable cardiac muscle.
During healing, heart can rupture (usually in first week as no scar has formed yet)
Ventricular rupture can also occur weeks/months after, when collagen has replaced all the necrotic cardiac muscle- due to the fact that collagen is non-contractual and therefore will always be a weakness at the scar/ cardiac muscle interface.

Question 21

Complications involving tissue repair: adhesion formation

Answer 21

Scar tissue within a body cavity and links tissues/ organs together that are not normally joined. Eg bacterial infections, endometriosis etc.
haemorrhagic/ fibrinous exudates that accumulate in body cavities stimulate an inflammatory reaction that results in acute inflammatory cells infiltrating the fibrinous scaffold.
Plasmin is deficient in injured tissues and therefore fibrin remains in the exudate and stimulates endothelial cells from surrounding tissues to eventually organise and form scar tissue.

Question 22

Complications involving tissue repair: Hypertrophic scar and keloid formation

Answer 22

Hypertrophic scarring is an imbalance between collagen lysis and collagen synthesis, resulting in overproduction of collagen in healing skin wound, involves only injured are of the wound. Keloid encompasses the injured tissue plus the uninjured normal peripheral skin around a wound.