Regeneration and Repair

Regeneration Ph/Pa

Replacing lost cells with identical cells. Ph: Epidermis, blood, glandular eipthelium/mucosa, endometrial lining in menstruation. Pa: Replacement of liver cells after acute hepatitis

Repair Ph/Pa

Cells lost are replaced by identical AND different cells. ALWAYS pathological: Cirrhosis of the liver in hepatitis, or after high alcohol intake.

Labile Cells

Remain in the cell cycle, constantly renewed ex blood, skin, epithelial, connective tissue; fibrous, osseous, cartilage, vasculature tissue.

Stable Cells

in G0 of the cell cycle, not currently in the cell cycle but can be stimulated to be so by growth factors. ex kidney, smooth muscle.

Permanent Cells

Cannot divide post-natal life ex Muscle, nerve cells, cardiac muscle.

Labile cells have been damaged but the ECM remains intact, what will occur?

Regeneration as in acute hepatitis

Stable cells have been damaged but the ECM remains intact, what will occur?

Regeneration as in acute hepatitis

Labile cells along with the ECM, have been damaged, what will occur?

Repair or regeneration & Fibrosis as in chronic hepatitis which causes Cirrhosis

Stable cells along with the ECM, have been damaged, what will occur?

Repair or regeneration & Fibrosis as in chronic hepatitis which causes Cirrhosis

Permanent cells have been damaged, what will occur?

Regardless of whether the ECM has been damaged, repair or Fibrosis (ex myocardial infarction) or just plain Loss of tissue will occur (cerebral infarction).

Mechanisms in repair in labile and stable cells.

1. Cell proliferation (occurs by growth and stimulatory factors and cell-cell interactions like density dependent contact inhibition or cell-matrix interactions like integrin receptors, such as the fibronectin receptor, on cells which bind adhesive glycoproteins on the ECM)
2. Repair of connective tissue
a) Ganulation tissue: Angiogenesis (VEGF and b-FGF bind proteoglycans of the basal lamina and are released when damaged. They mediate the budding of new vessels from pre-existing vessels. New vessels are immature and leaky giving edematous appearance.)
b) Granulation tissue: Fibrosis (Inflammatory cells release growth factors stimulating proliferation of fibroblasts and their deposition of ECM.)
c) Scarring/Cirrhosis tissue: Maturation & Organization/Remodeling (Inflammatory and some epithelial cells produce zinc dependent enzymes called metalloproteinases which degrade fibrillar collagens 1, 2, 3, 4 and fibronectin, by doing so they remove debris and remodel the connective tissue).

Describe the steps in skin wound healing (labile cells where ECM has been damaged)

1. Hemostasis: crust formation/scab, useful to stop bleeing and prevent infection, only occurs in vascularized tissue where vessels are damaged and in tissue dry enough for scabbing.
2. Acute Inflammation and Necrosis: in which dead tissue removed by sloughing, inflammation marking a zone of demarcation, dead tissue, debris and exudate is removed by phagocytosis and liquefaction.
3. Repair/Formation of Granulation Tissue: cells migrate and proliferate, specifically fibroblasts which lay down collagen III, endothelium which migrates in arcs and after some lag is home to angiogenesis forming new capillaries, and epithelium which migrates in sheets immediatly or between teh scab and granulation tissue causing the scab to drop off (the direction of fibers is determined by tissue tension). The granulation tissue bleeds easily, is insensitive to pain (no nerve endings), and is resistant to infection.
4. Cicatrization/Formation of Scar Tissue: via gradual closing of small vessels, collagen converted from type III to type I.

Why does scab formation not occur in the cornea?

The cornea is not vascularized

Why does scab formation not occur in the uterine mucosa?

The uterine mucosa is not dry enough to promote scabbing.

Adhesions

Adhesions can form in repair of serous membranes causing fibrous connection between two serosal surfaces such as after abdominal surgery

Keloid

Excess scar formation, through connective tissue proliferation in the dermis. Doesn't respect boundary. Red, raised, firm, smooth, shiny, a sharp irregular outline. Lesion consists of irregularly arranged, broad, homogenous collagen fibres, there are more fibroblasts and capillaries than in typical dermis. 10% of population is more susceptible.

Dehiscence

Deficient scar formation, wound re-opens

Hypertrophic scar

Excess scar formation, respecting boundaries.

Contractures

Permanently contracted state, loss of function.

Whats the difference between primary and secondary repair?

Primary repair occurs when the edges of the wound are in apposition (close together) by circumstance or by sutures in surgery, it minimizes granulation tissue and therefore scarring. Secondary repair occurs when the edges of the wound are not in apposition and cannot be closed, repair occurs only by granulation tissue and causes a larger scar. In secondary repair, closure follows latency, contraction by myofibroblasts, and epidermization periods.

Do wounds regain full strength?

No, they regain 70-80% tensile strength within 3 months. Likely due to the difference in collagen laid. Most wounds involving skin, fascia, or tendon dont regain full strength.

What local factors negatively influence rate of wound healing?

1. Decreased blood supply,
2. denervation,
3. local infection,
4. foreign bodies,
5. necrotic tissue,
6. mechanical stress,
7. hematoma,
8. increased wound size

What systemic factors negatively influence rate of wound healing?

1. Decreased blood supply,
2. age,
3. anemia,
4. malignancy,
5. malnutrition,
6. obesity,
7. infection,
8. organ failure.

What do we do to reduce factors that slow and complicate wound healing?

1. Protect and irrigate the wound to reduce infection; immobilize the injured area and avoid manipulation to reduce mechanical stress;
2. drain exudate and pus to help in healing and reduce infection;
3. administer antibiotics to reduce infection; remove noxious materials (includes debridement and removal of devitalized tissue) to reduce infection, reduce foreign bodies, and aid in healing;
4. control bleeding and remove excessively clotted blood to reduce hematoma;
5. elevate to aid in drainage to aid in healing;
6. apply appropriate themal modification to aid in healing;
7. main optimal nutritional status for age.