Regeneration and healing

What are the 2 processes of damaged tissue repair after inflammation and what are they both triggered by?

1. Regeneration

2. Scarring (fibrosis)

Both processes triggered by :

1. Cytokines and growth factors (produced mainly by macrophages)

• Anti-inflammatory cytokines to terminate inflammation.

• Growth factors to promote repair

Regeneration most seen in epithelium of … and explain with examples the 3 types (labile, stable and permanent) proliferative capacity of tissue?

Regeneration seen: in epithelia of skin liver and intestine as have proliferative capacity and contain abundant tissue stem cells.

Proliferative capacity of tissue:

1. Labile tissue (continuously dividing tissue)

• Cells continuously being lost and replaced → g1 growth

• Eg: Heamatopoietic cells (bone marrow), and surface epithelia (epidermis, ailementary tract, respiratory tract , urinary tract)

2.Stable tissues:

• Minimal replicative and only proliferate in response to injury (stimulus)

• Cells Quiscent (inactive) → G0 phase

• Eg: Kidney, fibroblast, vascular endothelium, parenchyma of solid tissue, smooth muscle

3.Permanent tissues:

• Terminally differentiated and nonproliferative in postnatal life → Irreversible injury leading to scar

• E.G: neurons , cardiac muscle and skeletal muscle cells

Fibrous tissue

1. Why it happens?

2. Repair by connective tissue deposition

3. Repair sequence

4. Scar vs Fibrosis

Fibrous Tissue (scar) is formed: if the tissue is unable to regenerate/ the structural framework is irreversibly damaged.

Repair by connective tissue deposition consists of

1.Formation of new blood vessels (angiogenesis)

2.Migration and proliferation of fibroblasts → Collagen synthesis

3.Deposition of Extracellular Matrix (scar formation)

4.Maturation and reorganization of the fibrous tissue(remodeling)

(Repair sequence)

1. During initial 3-5 days of repair injury site filled with newly formed capillaries, macrophages and fibroblast embedded in granulation tissue (loose extracellular matrix).

2. Gradually collagen is laid down by fibroblast to form scar.

Scar vs Fibrosis

Collagen deposited in peripheral site (limb, skin) = scar,

Collagen deposited in parenchymal organ in abnormally large amounts (liver, lung), = fibrosis

Fibrosis / Scarring (Describe growth factors involved in repair and angiogenesis)

Growth factors

• tgf-β and fibroblast growth factor (FGF) act on fibroblasts in connective tissue → Stimulate their proliferation and collagen synthesis.

• VEGF → Formation of new blood vessels that provide nutrition to proliferating fibroblast

Angiogenesis

1. Vasculogenesis : Vascular network formed from angioblast (endothelial cell precursors)

2. Neovascularization : Pre-existing vessels send out capillaries to produce new vessels

Cutaneous wound healing : Healing by 1st intention

Healing by 1st intention

Occurs : Clean, uninfected surgical incision of skin closed with surgical sutures

Steps:

1. Wound initially sealed by blood clot → neutrophil and macrophage arrive

2. → small amount of granulation tissue formed → replaced by thin scar

3. → surface epithelial cells regenerate and bridge incisional gap

Cutaneous wound healing : Healing by 2nd intention

Healing by 2nd intention

Occurs: More severe, deep skin injuries where edges can’t be closed

Same sequence of events but…

1. Granulation tissue much larger and persists for longer

2. More collagen is laid down

3. Fibrous scar is thicker

By about 4 to 6 weeks, the skin wound is closed with a dense scar.

The skin wound contracts cuz of myofibroblasts action in the connectivetissue.

Factors impairing repair

1. Mechanical factors: like excessive movement and pressure

2. Infection: prolongs inflammation and causes progressive tissue injury

3. Diabeties :

• Underlying metabolic abnormality

• vascular narrowing leading to reduced blood supply,

• ↑ suceptible to infection due to ↓ neutrophils function and impaired cytokine production by macrophage

4. Poor perfusion (adequate blood supply) due to atherosclerosis , diabetes..

5. 

Excessive repair process conditions

1. Hypertrophic scars

• Develop following injury

• Usually regress slowly

• Eg:knee joint

2. Keloids

• Scar tissue grows beyond injury margins

• Fails to regress

3. Excess scaring leads to serious disorders such as Pulmonary fibrosis , Liver Cirrhosis