Fatima Obeidat. MD Lecture I Healing and Repair Fatima Obeidat. MD Lecture I

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

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

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

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

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

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.

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

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.

- 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

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

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

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

b. Endothelial cells, c. Fibroblasts, and d. Smooth muscle cells NOTE 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

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

- 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

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 .

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

- 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

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

1. type IV present in basement membranes 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

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.

- 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}

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

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