REPAIR AND HEALING
It is the process by which the body forms new cells to replace structures damaged in a pathologic process.
This involves 2 processes, separately or often in variable combination:
■ Regeneration: Healing by cells of the same type.
■ Fibrosis (organization): Healing by fibrous tissue scar developing form granulation tissue.
In order to understand the mechanism of repair we have to know the cell cycle.
The period between 2 successive cell divisions divided into 4 unequal phases:
■ M (mitotic) phase: Interval between onset and conclusion of mitosis.
■ Gl (presynthetic) phase: Following mitosis. The cell is devoted to specialized activities.
■ S (synthetic) phase: Doubling of DNA.
■ G2 (premitotic) phase: Preceding next mitosis.
According to the proliferative potential of different cells, they are divided into three types:
■ Labile cells:
– Proliferate throughout life.
– Replace cells that are continuously lost.
– Proceed in cell cycle from one mitosis to the other.
e.g. epidermal cells, lining of GIT, endometrial cells, and hemopoietic cells (bone marrow).
■ Stable cells:
– Do not multiply under normal conditions.
– Capable of rapid division after tissue loss i.e if stimulated.
– Considered to be in the “G 0 phase”
– Can re-enter the cycle at Gl after an appropriate stimulus (tissue loss).
e.g. liver cells, kidney cells, pancreatic cells, vascular endothelium, fibroblasts, osteoblasts, chondroblasts, and smooth muscle cells
■ Non-dividing (permanent) cells:
– Do not multiply in postnatal life.
– Considered to have “exited” the cycle at some point in intrauterine development.
e.g. nerve cells, cardiac muscle fibers, skeletal muscle fibers.
Most tissues in the body contain different proportions of the different cell types.
Regeneration occurs in tissues composed of labile or stable cells. Fibroplasia occurs in:
1. Tissues composed of permanent cells.
2. Presence of factors that prevent complete restoration e.g. interruption of blood supply
Control of cell growth:
Many mediators affect cell growth.
The most important are polypeptide growth factors:
■ Circulating in serum or produced locally.
■ Induce cell proliferation by affecting expression of genes involved in normal cell growth (proto-oncogenes).
■Most also stimulate cell migration and differentiation (pleiotropic effect).
Cell proliferation is directed by a family of proteins called cyclines (control phosphorylation of proteins involved in mitosis).
■ Macrophage derived growth factor (MDGF)
■ Platelet derived growth factor (PDGF)
■ Epidermal growth factor (EGF)
■ Fibroblastic growth factor (FGF)
■ Vascular endothelial growth factor (VEGF)
■ Transforming growth factor-B (TGF-B)
■ Regulate cell growth e.g. decreased inhibitors lead to cell growth.
■ Are also largely polypeptide factors that use receptors.
■ The best studied are TGF-B and interferon gamma. Granulation Tissue:
Mesenchymal tissue consisting of:
■ Newly formed capillaries which arise from endothelial cells lining nearby blood vessels. These proliferate to form solid buds that branch, anastomose and become canalized.
■ Fibroblasts which arise from activation, proliferation and migration of nearby “fibrocytes”
■ Ground substance and small amount of young collagen formed by fibroblasts.
■ Few inflammatory cells and macrophages.
It is formed in: Wound healing, healing of abscess, chronic inflammation, replacement of fibrin and necrotic tissue (organization).
The granulation tissue appears soft, pink and granular. Progressive fibrosis then occur leading to the formation of a strong avascular fibrous scar.