Wound Healing

Sofian Anwar
Overview of Tissue Repair
• Repair,  also called healing  restoration tissue
architecture&function
• Critical to the survival of an organism
• inflammatory response to microbes and injured tissues not only
serves to eliminate these dangers but also sets into motion the
process of repair
• Repair of damaged tissues:
• Regeneration by proliferation of residual (uninjured) cells and maturation of
tissue stem cells
• Deposition of connective tissue to form a scar
Overview of Tissue Repair
• Repair of damaged tissues
occurs by two processes:
• regeneration, which restores
normal cells.
• scarring, the deposition of
connective
tissuefibrosis/organization
Fibrosis : menggantikan jaringan
asal (liver, lungs,kidney,etc)
Organization : develops in a
tissue space occupied by an
inflammatory exudate
OVERVIEW
• Regeneration
• Occurs by proliferation of cells that survive the injury and retain the capacity
to proliferate
• Example: epithelia of the skin and intestines, liver
• Connective tissue deposition •
• If the supporting structures of the tissue are severely damaged, repair occurs
by the laying down of connective (fibrous) tissue → scar formation
• Fibrosis: extensive deposition of collagen
• Example: lungs, liver, kidne
Cell and Tissue Regeneration
• The regeneration of injured cells and tissues involves cell proliferation,
which is driven by growth factors and is critically dependent on the
integrity of the ECM, and by the development of mature cells from
tissue stem cells.
• The ability of tissues to repair themselves is determined, in part, by
their intrinsic proliferative capacity and the presence of tissue stem
cells
Cell and Tissue Regeneration
Cell Proliferation: Signals and Control Mechanisms
• Labile (continuously dividing) tissues  hematopoietic cells in the
bone marrow and the majority of surface epithelia,
• Stable tissues  Quiescent (in the G0 stage of the cell cycle) and have
only minimal proliferative activity in their normal state. parenchyma
of most solid tissues, such as liver, kidney, and pancreas.
They also include endothelial cells, fibroblasts, and smooth
muscle cells
• Permanent tissues  terminally differentiated and nonproliferative in
postnatal life (brain or heart is irreversible and results in a scar
because neurons and cardiac myocytes cannot regenerate)
Cell cycle
• Macrophages, residual epithelial and stromal cells are activated by
the damage → growth factors → together with ECM → signaling
pathways → cell cycle or block cell cycle
Mechanisms of Tissue Regeneration
• Regeneration of the liver occurs by two major mechanisms:
• Proliferation of remaining hepatocytes
• Repopulation from progenitor cells
• Restoration of normal tissue structure can occur only if the residual tissue is structurally
intact
KEY CONCEPTS
• Tissues are classified as labile,stable, and permanent, according to the proliferative
capacity of their cells.
• Continuously dividing tissues (labile tissues) contain stem cells that differentiate to
replenish lost cells and maintain tissue homeostasis.
• Cell proliferation :
• controlled by the cell cycle
• stimulated by growth factors
• interactions of cells with the ECM.
• Regeneration of the liver is a classic example of repair by regeneration.
triggered by cytokines and growth factors produced in response to loss of liver
mass and inflammation. In different situations, regeneration may occur by
proliferation of surviving hepatocytes or repopulation from progenitor cells
Repair by Connective Tissue Deposition
• 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
Vasoconstriction
• When endothelial injury occurs, the endothelial cells secrete von
Willebrand factor, which causes platelet adherence during the initial
formation of a clot. The vasoconstriction that occurs during
hemostasis is a brief reflexive contraction that causes a decrease in
blood flow to the area
Platelet Plug Formation
• When the lining of a blood vessel breaks and endothelial cells are
damaged, revealing sub-endothelial collagen proteins from the
extracellular matrix, thromboxane causes platelets to swell, grow
filaments, and start aggregating. Von Willebrand factor causes them
to adhere to each other and the walls of the vessel. This continues as
more platelets congregate and undergo these same transformations.
This process results in a platelet plug that seals the injured area. If the
injury is small, the platelet plug may be able to form within several
seconds
Repair by Connective Tissue Deposition
• A response of vascularized tissues to infection and damaged tissues
that brings cells and molecules of host defense from the circulation to
the sites where they are needed, in order to eliminate the offending
agents.
• Sequential steps:
• 1.Recognition of the offending agent in the extravascular tissues by host cells
and molecules.
• 2.Recruitment of leukocytes and plasma proteins from the circulation to the
damaged site.
• 3.Activation of the leukocytes and proteins to eliminate the offending agent.
• 4.The damaged tissue is repaired
Sequence of events in an inflammatory reaction.
Sentinel cells in tissues (macrophages, dendritic cells, and other
cell types) recognize microbes and damaged cells and liberate
mediators, which trigger the vascular and cellular reactions of
inflammation.
INFLAMMATION
• HYPEREMIA
• Hyperemia in inflammation is associated with microvascular changes
which occur in Lewis’ triple response: flush, flare and weal
• The stroke is marked momentarily by a white line due to
VASOCONSTRICTION
• The flush, a dull red line, immediately follows and is due to CAPILLARY
DILATATION
• The flare, a bright red irregular surrounding zone, is due to
ARTERIORAL DILATATION
Repair by Connective Tissue Deposition
• If regeneration is not enough → replacement with connective tissue
→ formation of a scar or combination of regeneration of some
residual cells and scar formation.
• Repair :
• 24 hours of injury → emigration & induction of fibroblast, and endothelial cell
proliferation
• 3-5 days → granulation tissue
• Steps in scar formation:
• 1. Angiogenesis
• 2. Formation of granulation tissue
• 3. Remodeling of connective tissue
Remodeling of Connective Tissue
• The outcome of the repair process is influenced by a balance between
synthesis and degradation of ECM proteins.
• After its deposition, the connective tissue in the scar continues to be
modified and remodeled.
• The degradation of collagens and other ECM components is
accomplished by a family of matrix metalloproteinases (MMps),
produced by a variety of cell types (fibroblasts, macrophages,
neutrophils, synovial cells, and some epithelial cells).
• MMPs can be rapidly inhibited by specific tissue inhibitors of
metalloproteinases (TIMPs), produced by most mesenchymal cells
FRACTURES and BONE HEALING
Fractures are defined :
• as loss of bone integrity.
• They are some of the most common pathologic conditions affecting bone.
• Type of fracture :
• Simple: the overlying skin is intact.
• Compound: the bone communicates with the skin surface.
• Comminuted: the bone is fragmented.
• Displaced: the ends of the bone at the fracture site are not aligned.
• Stress: a slowly developing fracture that follows a period of increased physical
activity in which the bone is subjected to repetitive loads.
• Greenstick: extending only partially through the bone, common in infants when
bones are soft.
Figure 26.18 The reaction to a fracture begins with an organizing
hematoma. Within 2 weeks, the two ends of the bone are bridged
by a fibrin meshwork in which osteoclasts, osteoblasts, and
chondrocytes differentiate from precursors. These cells produce
cartilage and bone matrix, which, with adequate immobilization,
remodels into normal lamellar bone.