BASIC MECHANISM OF DISEASE

LUKA & PENYEMBUHAN LUKA

dr. A. Visi Kartika, M.Kes., Sp.PA

AnatomIcal Pathology Dept.

Medical Faculty of Universitas Hasanuddin
 Tissue Repair
• Def: restoration of tissue architecture and
function after an injury
• Repair occurs by two types of reactions:
1. Regeneration by proliferation of residual
(uninjured) cells and maturation of tissue stem
cells
2. The deposition of connective tissue to form a
scar
• Tissues are classified as labile, stable, and permanent,
according to the proliferative capacity of their cells
• Cell proliferation is driven by signals provided by
growth factors and from the extracellular matrix
• In the process of regeneration, proliferation of
residual cells is supplemented by development of
mature cells from stem cells
• Restoration of normal tissue structure can occur only
if the residual tissue is structurally intact, if the entire
tissue is damaged by infection or inflammation,
regeneration is incomplete and is accompanied by
scarring.
• If repair cannot be accomplished by regeneration alone
it occurs by replacement of the injured cells with
connective tissue, leading to the formation of a scar, or
by a combination of regeneration of some residual
cells and scar formation
• Scarring may happen if the tissue injury is severe or
chronic and results in damage to parenchymal cells and
epithelia as well as to the connective tissue framework,
or if nondividing cells are injured.
• The main components of connective tissue repair are
angiogenesis, migration and proliferation of fibroblasts,
collagen synthesis, and connective tissue remodeling.
A, Granulation tissue showing numerous blood vessels, edema, and a loose extracellular matrix containing occasional

inflammatory cells. Collagen is stained blue by the trichrome stain; minimal mature collagen can be seen at this point. B,

Trichrome stain of mature scar, showing dense collagen, with only scattered vascular channels.
• Macrophages play a central role in repair by
clearing offending agents and dead tissue,
providing growth factors for the proliferation
of various cells, and secreting cytokines that
stimulate fibroblast proliferation and con-
nective tissue synthesis and deposition.
Step of Angiogenesis
 Deposition of Connective tissue
1. Migration and proliferation of fibroblasts into
the site of injury and
2. Deposition of ECM proteins produced by
these cells.
• Transforming growth factor-/3 (TGF-/3) is the
most important cytokine for the synthesis and
deposition of connective tissue proteins.
Factors That Influence Tissue Repir
• Infection
• Diabetes
• Nutritional status
• Glucocorticoids (steroids)
• Mechanical factors
• Poor perfusion
• Foreign bodies
• The type and extent of tissue injury
• When the injury involves only the epithelial
layer, the principal mechanism of repair is
epithelial regeneration, also called primary
union or healing by first intention.
• When cell or tissue loss is more extensive,
such as in large wounds, abscesses, ulceration,
and ischemic necrosis (infarction) in
parenchymal organs, the repair process
involves a combination of regeneration and
scarring. In healing of skin wounds by second
intention, also known as healing by secondary
union
Healing of skin ulcers. A, Pressure ulcer of the skin, commonly found in diabetic patients. The histologic slides show a skin
ulcer with a large gap between the edges of the lesion (B), a thin layer of epidermal reepithelialization and extensive
granulation tissue formation in the dermis (C), and continuing reepithelialization of the epidermis and wound contraction
(D).
• Fibrosis is a pathologic process induced by
persistent injurious stimuli such as chronic
infections and immunologic reactions, and is
typically associated with loss of tissue
 Abnormalities in Tissue Repair
• Inadequate formation of granulation tissue or
formation of a scar can lead to two types of
complications: wound dehiscence and
ulceration
• Excessive formation of the repair process can
give rise to hypertrophic scas and keloids
• Exuberant granulation
TERIMAKASIH