HEALING AND REPAIR FLASH POINTS
BY DR EJAZ WARIS – PROFESSOR SMDC
1. Injury to cells and tissues sets in motion a series of events that contain
the damage and initiate the healing process. This process can be broadly separated into
regeneration and repair
2. Regeneration refers to the proliferation of cells and tissues to replace lost structures.
Repair most often consists of a combination of regeneration and scar formation by the
deposition of collagen
3. In adult tissues the size of cell populations is determined by the rates of cell proliferation,
differentiation, and death by apoptosis
4. The tissues of the body are divided into three groups on the basis of the proliferative activity
of their cells: continuously dividing (labile tissues), quiescent (stable tissues), and nondividing
(permanent tissues).
5. In continuously dividing tissues cells proliferate throughout life, replacing those that are
destroyed. These tissues include surface epithelia, such as stratified squamous epithelia of the
skin, oral cavity, vagina, and cervix; the lining mucosa of all the excretory ducts of the glands of
the body (e.g., salivary glands, pancreas, biliary tract); the columnar epithelium of the GI tract
and uterus; the transitional epithelium of the urinary tract, and cells of the bone marrow and
hematopoietic tissues.
6. Quiescent tissues normally have a low level of replication; however, cells from these tissues
can undergo rapid division in response to stimuli and are thus capable of reconstituting the
tissue of origin. In this category are the parenchymal cells of liver, kidneys, and pancreas
7. Nondividing tissues contain cells that have left the cell cycle and cannot undergo mitotic
division in postnatal life. To this group belong neurons and skeletal and cardiac muscle cells
8. Stem cells are characterized by their self-renewal properties and by their capacity to generate
differentiated cell lineages
9. The inner cell mass of blastocysts in early embryonic development contains pluripotent stem
cells known as ES cells.[
10. In the adult organism, stem cells are present in tissues that continuously divide such as the
bone marrow, the skin, and the lining of the GI tract.
11. The replication of cells is stimulated by growth factors or by signaling from ECM
components through integrins
12. The cell cycle consists of G1 (presynthetic), S (DNA synthesis), G2 (premitotic), and M
(mitotic) phases. Quiescent cells that have not entered the cell cycle are in the G0 state
13. The proliferation of many cell types is driven by polypeptides known as growth factors.
14. Cram table 3-1 for growth factors.
15. The ECM is composed of three groups of macromolecules: fibrous structural proteins, such
as collagens and elastins that provide tensile strength and recoil; adhesive glycoproteins that
connect the matrix elements to one another and to cells; and proteoglycans and hyaluronan that
provide resilience and lubrication
16. Most adhesion proteins, also called CAMs (cell adhesion molecules), can be classified into
four main families: immunoglobulin family CAMs, cadherins, integrins, and selectins
17. The name cadherin is derived from the term “calcium-dependent adherence protein.” This
family contains almost 90 members, which participate in interactions between cells of the same
type
18. Scar formation consists of the followinf steps : angiogenesis , migration and proliferation into
the site of injury , deposition of ECM proteins , collagen synthesis and connective tissue
remodeling.
19. TGB beta is the most important cytokine for the synthesis and deposition of ECM proteins.
20. MMPs are matrix mettaloproteinases which degrade collagen and other ECM proteins.
21. The simplest type of cutaneous wound repair is the healing of a clean, uninfected surgical
incision approximated by surgical sutures . Such healing is referred to as healing by primary
union or by first intention.
22. The healing of larger wounds involves a more intense inflammatory reaction, the formation
of abundant granulation tissue (described below), and extensive collagen deposition, leading to
the formation of a substantial scar, which generally contracts. This form of healing is referred to
as healing by secondary union or by second intention
23.
--Monocyte chemotaxis
Chemokines, TNF, PDGF, FGF, TGF-β
-Fibroblast migration/replication
PDGF, EGF, FGF, TGF-β, TNF, IL-1
-Keratinocyte replication
HB-EGF, FGF-7, HGF
-Angiogenesis
VEGF, angiopoietins, FGF
-Collagen synthesis
TGF-β, PDGF
-Collagenase secretion
PDGF, FGF, TNF; TGF-β inhibits
24.Specialized type of tissue called granulation tissue, which is a hallmark of tissue repair. The
term derives from its pink, soft, granular appearance on the surface of wounds. Its characteristic
histologic feature is the presence of new small blood vessels (angiogenesis) and the
proliferation of fibroblasts
25.Macrophages are key cellular constituents of tissue repair, clearing extracellular debris,
fibrin, and other foreign material at the site of repair, and promoting angiogenesis and ECM
deposition
26.Migration of fibroblasts to the site of injury is driven by chemokines, TNF, PDGF, TGF-β, and
FGF. Their subsequent proliferation is triggered by multiple growth factors, including PDGF,
EGF, TGF-β, FGF, and the cytokines IL-1 and TNF
27The initial steps of wound contraction involve the formation, at the edge of the wound, of a
network of myofibroblasts that express smooth muscle α-actin and vimentin.
28The replacement of granulation tissue with a scar involves changes in the composition of the
ECM. The balance between ECM synthesis and degradation results in remodeling of the
connective tissue framework – an important feature of tissue repair.
29.Degradation of collagen and other ECM proteins is achieved by matrix metalloproteinases
(MMPs), a family of enzymes that includes more than 20 members
30.Once formed, activated collagenases are rapidly inhibited by a family of specific tissue
inhibitors of metalloproteinases, which are produced by most mesenchymal cells, thus
preventing uncontrolled action of these proteases.
31.The adequacy of wound repair may be impaired by systemic and local host factors.
32.Systemic factors are :
33.Nutrition , metabolic status , hormones and circulatory status.
34..Local factors are :
35.Infection , mechanical factors ,foreign bodies , size – location and type of wound.
36,/.Complications in wound healing can arise from abnormalities in any of the basic
components of the repair process. These aberrations can be grouped into three general
categories: (1) deficient scar formation, including wound dehiscence and ulceration(2) excessive
formation of the repair components, including keloid and hypertrophic scar (3) formation of
contractures. 4) exuberant granulation tissue including proud flesh and desmoids.
