Replacement of injured or dead tissue

Body must do this to survive

Both are healing processes.

Regeneration: Uninjured parenchymal (functional) cells may replicate to replace injured cells if stroma (connective tissue and blood vessels) is not injured.  Function is restored, no scarring, can occur if parenchymal cells can replicate.

Repair: When lost parenchymal cells cannot replicate and be replaced.  Replacement by fibrous connective tissue called repair by fibrosis.  Scar formation occurs with possible impairment of tissue function.

continously dividing

examples: bone marrow, epithelia of skin, mucosa of GI tract

these can usually replace lost cells

healing by regeneration can usually occur

replicate at slow rate

examples: most glands, liver, smooth muscle, osteoblasts, vascular endothelial cells

these can usually replace lost cells

healing by regeneration can usually occur

do not divide after birth

examples: neurons, cardiac muscle, skeletal muscle

healing by regeneration cannot occur

healing is by repair and fibrosis

1. tissue damage, bleeding, clot formation

1. around clot, formation of exudate, which becomes organized, new blood vessels form, resulting in granulation tissue

1. phagocytes eliminate clot

1. fibroblasts in granulation tissue make procollagen which is organized into collagen fiber bundles outside of cell

1. ECM strengthens collagen

removal of clot and replacemtn by fibrous scar tissue is called reorganization

Regeneration of blood supply to injured area, whether healing by regeneration or by repair.

endothelial cells from undamaged vessels form buds that elongate.-may contact parent vessel to form new channel

-may contact bud from another parent to form new channel

-may become isolated and degenerate.

new blood vessels are slowly modified into arterioles, venules, capillaries

healing region needs more blood vessels, after healing reabsorption of blood vessels and paler appearance of tissue 

Innervation by vasomotor neurons

Lymphatic vessels similarly regenerate

zone of active mitosis of epithelial cells develops at edge of wound

these cells migrate across surface of granulation tissue or in case of minor skin abrasion, across surface of intact dermis

these cells secrete new basement membrane

after closing of gap, new cells move vertically to surface to restore normal arrangement

This occurs where wound is clean and edges are close together (e.g. surgical incision).

Healing by repair and fibrosis, angiogenesis and restoration occurs.

Additionally, granulation tissue appears in 2-3 days, fibroblasts in granulation tissue make procollagen organized into collagen fiber bundles outside of cell, ECM strengthens collagen, and there is realignment of collagen fibers after about 6th day, increasing strength.

Surface restoration is occurring.  If a skin wound: keratinocytes of epidermis produce new keratin, which loosens scab, melanocytes of epidermis do not regenerate, scar area is pale

By 2nd week, changes in granulation tissue, fewer phagocytes, reabsorpion of blood vessels

Continued remodeling of collagen for about 3 months to maximal strength of scar, about 70-80% of normal.

Healing by secondary intention occurs with larger wounds with edges not close together or infection presence of foreign bodies in wound.

examples: Lage, dirty, or infected skin wounds, peptic ulcer in GI tract

Healing is similar to primary intention but healing is slower, much more inflammation and formation of granulation tissue, many more fibroblasts are involved to close defect.

Since wounds must contract, myofibroblasts attach to edges of wound and contract, begins 2-3 days after injury

Shape of final scar is different than original wound due to this contraction.  Circular wound does not fully close.

Bone is a connective tissue, therefore, prolonged healing due to limited blood supply

Medical intervention for reduction and immobilization of fracture site.

1st stage of healing: 4-5 days after fracture

-removal of blood and debris between bone ends

-formation of granulation tissue, blood vessels, activation and migration of osteoblasts to fracture area

2nd stage of healing: occurs over next 3 weeks

-osteoblasts make collagen and cartilage, stabilizes fracture, tissue is called osteoid/soft callus

-osteoid is ossified by osteoblasts to form hard callus (healing area is now enlarged but structurally weak)

3rd stage of healing: extends over months - years

-osteoblasts and osteoclasts remodel hard callus to restore normal bone structure

Connective tissue and healing is prolonged due to limited blood supply.

cartilage: healing by fibrous repair, fibroblasts of perichondrium produces scar tissue, some loss of function

adipose tissue: cells cannot divide, but precursor cells produce new adipose cells, fibrosis does not occur

Mostly made up of labile cells

examples: epithelia of epidermis, mucous membranes, respiratory surfaces, other body surfaces

Regarding respiratory/lung surfaces: epithelia can regenerate with superficial injury but fibrosis and scarring if basement membrane and ECM are damaged

Most glands are made up of quiescent/stable cells, therefore can readily regenerate with minor injury.

More extensive injury: regeneration with some loss of normal structure and function

Severe, sustained injury: 

-loss of parenchymal, stroma, ECM

-contracted scar tissue

-loss of function with irregular surface depressions

• Parathyroid
• Adrenal Medulla
• Posterior pituitary

No mitosis is possible in nervous tissue.

Replacement of damaged neurons by neuroglia called gliosis, which can block axon regeneration

In peripheral nervous system: regeneration of cut nerve process (axon/dendrite) can occur if supporting connective tissue and Schwann cells are intact

After cut: degeneration of process and myelin sheath distal to cut, injured Schwann cells are replaced and follow original path

New sprout from process finds canal formed by Schwann cells and connective tissue, grows along this path to reinnervate muscle or other structure

If larger nerve is severed and if ends remain seperated, THEN regenerating processes may grow into new scar tissue to form traumatic neuroma.

Cardiac and skeletal muscle cells: Cannot regenerate, fibrous repair with injury, possible compensation with hypertrophy

Smooth muscle cells: Some regeneration is possible, sometimes healing by fibrous repair

• large size of wound
• tension
• infection
• poor blood flow
• advanced age
• poor nutrition
• movement
• diabetes
• corticosteroid use

deficient scar formation: opening of healing wound

excess scar formation: exuberant granulation, keloids

contractures:large scars can interfere with movement

adhesions: union of 2 membranes that normally move freely against each other

"proud flesh"

too much granulation tissue

protrusion of irregular scar tissue from skin surface due to overproduction of collagen

excessive production or sensitivity to TGF-B

clearance of debris

immobility

adequate blood supply

nutrients