Healing and Repair

1. Healing and Repair Fatima Obeidat. MD Lecture I

2. - Repair the damage is called healing - It refers to the restoration of tissue architecture and function after an injury.

3. - It occurs by two types of reactions: a. Regeneration of the injured tissue b. Scar formation by the deposition of fibrous tissue

4. a. Regeneration. : - Means ability of some tissues to replace the damaged cells and return to a normal state - It occurs by: 1. proliferation of residual (uninjured) cells that retain the capacity to divide 2. and by replacement from tissue stem cells

5. b. Scar formation: - Occurs by the laying down of fibrous tissue, which results in in scar formation - It occurs in the following situations a. If the injured tissues are incapable of regeneration, b. If the supporting structures of the tissue are severely damaged

6. NOTE: - Although the fibrous scar cannot perform the function of lost parenchymal cells, it provides enough structural stability that the injured tissue is usually able to function

7. The term fibrosis - Means extensive deposition of collagen that occurs a. In the liver, kidney and other organs as a result of chronic inflammation b. or in the myocardium after infarction.

8. The term organization : - It designates fibrosis developing in a tissue space occupied by an inflammatory exudate (as in organizing pneumonia affecting the lung).

9. Note - After many types of injury, both regeneration and scar formation contribute to the ultimate repair - Both processes(regeneration and scarring ) involve the proliferation of various cells and close interactions between cells and the ECM.

10. - The proliferation of cells in regeneration is driven by growth factors and is critically dependent on the integrity of the extracellular matrix. - The cell types that proliferate during repair include: a. The remnants of the injured tissue b. Vascular endothelial cells (to form new vessels) c. Fibroblasts (the source of the fibrous tissue

11. Proliferative Capacities of Tissues - The tissues of the body are divided into three groups. 1. Labile (continuously dividing) tissues.and include : a. Hematopoietic cells in the bone marrow b. The stratified squamous surfaces of the skin, and oral cavity

12. c. The cuboidal epithelia of the ducts draining exocrine organs ( salivary glands, biliary tract) d. The columnar epithelium of the gastrointestinal tract,

13. 2. Stable tissues: - Are quiescent and have only minimal replicative activity in their normal state.; -But these cells are capable of proliferating in response to injury or loss of tissue mass and these cells include: a. The parenchyma of most solid tissues, such as liver, kidney

14. b. Endothelial cells, c. Fibroblasts, and d. Smooth muscle cells NOTE. - With the exception of liver, stable tissues have a limited capacity to regenerate after injury

15. 3. Permanent tissues. - The cells of these tissues are terminally differentiated and nonproliferative in postnatal life and include a. Most neurons b. and cardiac muscle cells

16. - Thus, injury to brain or heart is irreversible and results in a scar. c. Skeletal muscle is classified as a permanent tissue, but satellite cells attached to the endomysium provide some regenerative capacity for this tissue

17. Role of the Extracellular Matrix in Tissue Repair - Repair depends on growth factor activity and on interactions between cells and ECM components. - The ECM is a complex of several proteins that assembles into a network that surrounds cells .

18. Roles of ECM a. Sequesters water, b. Provides and minerals giving rigidity to bone c. A reservoir for growth factors.

19. - ECM occurs in two basic forms: 1. Interstitial matrix: - Is present in the spaces between cells in connective tissue, and between epithelium and supportive vascular and smooth muscle structures

20. - Its major constituents are a. Fibrillar collagen (types I, II, III, and V) - Genetic defects in these collagens(type I) cause diseases such as osteogenesisimperfecta and Ehlers-Danlos syndrome

21. b. Nonfibrillar collagens, include 1. type IV present in basement membranes 2. type IX present in intervertebral disks) 3. type VII present indermal-epidermal junctions

22. 3. Elastin :A COMPONENT OF ELASTIC FIBERS - Confers ability for tissues to recoil and return to a baseline structure after stress . - Is important in the walls of large vessels (which must accommodate recurrent pulsatile flow), as well as in the skin, and ligaments.

23. - Elastic fibers consist of core of elastin surrounded by network of fibrillin glycoprotein. -Defects in fibrillin synthesis lead to skeletal abnormalities and weakened aortic walls (Marfan syndrome}

24. 2. Basement membranes: - Is an organized tissue around epithelial cells, endothelial cells, and smooth muscle cells, is synthesized by epithelium and mesenchymal cells - Its major constituents are amorphous nonfibrillar type IV collagen and laminin

25. 3.Adhesive Glycoproteins - Involved in cell-to-cell adhesion, the linkage of cells to the ECM,.and include : A, Fibronectin (a major component of the interstitial ECM) with two forms