PATH 3810 Tissue Repair and Healing

tissue repair

restoration of tissue architecture and functon after an injury

repair occurs by…

…regeneration or healing by scar formation, involving cell proliferation and cell-to-matrix interactions

fibrosis

extensive deposition of collagen in organs as a consequence of chronic inflammation

continuously dividing tissues

continuously being lost and replaced by maturation from stem cells and proliferation of mature cells

stable tissues

minimally replicative activity in normal state

permanent tissues

terminally differentiated and nonproliferative in postnatal life

polypeptide growth factors promote cell survival and proliferation by…

…binding to specific receptors and altering gene expression

autocrine signaling

the substance acts primarily on the cell that secretes it

paracrine signaling

substance acts on cells in the immediate vicinity of the cell that released the agent

endocrine signaling

regulatory substance is released into the blood stream and acts on target cells at a distance

fibroblast

spindle-shaped or stellate, most common connective tissue cell

fibroblast functions

synthesizes tropocollagen and extracellular matrix components

maintains and repairs connective tissue

extracellular matrix

dynamic, macromolecular complex that is synthesized locally

regulates proliferation, movement, and differentiation of cells inhabiting it

synthesis and degradation accompany healing and fibrosis

proteoglycans in the ECM act as…

…reservoirs for growth factors, such as FGF

repair by connective tissue

begins within 24 hours by the emigration of fibroblasts and proliferation of these and endothelial cells

granulation tissue showing numerous blood vessels, edema, and loose ECM

trichrome of a mature scar

granulation tissue

formed within 3-5 days, characterized by pink, soft, granular gross appearance and proliferation of fibroblasts and newly formed capillaries

granulation tissue at three scales

process of repair by connective tissue

1. angiogenesis

2. migration and proliferation of fibroblasts

3. deposition of ECM

4. remodeling: maturation and reorganization of connective tissue

angiogenesis

process by which preexisting vessels send out capillary sprouts to produce new vessels

steps in angiogenesis

1. vasodilation

2. migration of endothelial cells toward site of injury

3. proliferation of endothelial cells

4. inhibition of proliferation and remodeling into capillary tubes

5. recruitment of peri-endothelial cells

growth factors crucial to angiogenesis

vascular endothelial growth factor (VEGF)

basic fibroblast growth factor (FGF-2)

scar formation

occurs on granulation tissue framework

1. migration and proliferation of fibroblasts

2. deposition of ECM

cutaneous wound healing phases

1. inflammation

2. granulation

3. scar formation

first intention healing

healing of a clean, uninfected surgical incision

first intention healing process

1. incision fills with fibrin-clotted blood, then invaded by granulation tissue and covered by new epithelium

2. at 24 hours, neutrophils present and basal cells show increased mitotic activity

3. at 24-48 hours, epithelial cells proliferate

4. at day 3, neutrophils are replaced by macrophages

5. at day 5, angiogenesis occurs and collagen is more abundant

second intention healing

healing of excessive tissue loss, abscess formation, and ulceration

second intention healing process

1. larger clot or scab rich in fibrin forms at surface of wound

2. inflammation more intense due to greater necrotic debris, exudate, and fibrin

3. much larger amounts of granulation tissue to fill gaps, which may result in greater mass of scar tissue

4. wound contraction mediated by myofibroblasts

epithelial ulcer

keloid

raised scars that form from excessive amounts of collagen

exuberant granulation on proud flesh

excessive granulation tissue that protrudes above the level of skin and hinders re-epithelialization

keloid

exuberant granulation tissue

A tissue contains cells that are normally quiescent in the G0 phase but can re-enter the cell cycle following injury. Which type of tissue is this?

Stable tissue

Which of the following are required for healing by regeneration?​

both a and b​

A horse develops a large mass of proliferating tissue that extends above the surface of a chronic skin ulcer and interferes with re-epithelialization. What is this lesion called?

Exuberant granulation tissue (proud flesh)

Which is NOT a feature of healing by first intention?​

extensive tissue loss ​

Which cell is primarily responsible for synthesizing tropocollagen and other extracellular matrix components during tissue repair?

Fibroblast