Healing

HEALING / REPAIR
Restoration of tissue architecture and function after an
injury.
Repair of damaged tissues following reactions:
1) Regeneration by proliferation of residual (uninjured) cells
2) Maturation of tissue stem cells
3) Deposition of connective tissue to form a scar

REGENERATION.
Ability to replace the damaged
components and essentially return to a
normal state; this process is called
Regeneration

Regeneration occurs by proliferation of cells that
survive the injury and retain the capacity to
proliferate,
for example, in the rapidly dividing epithelia of the
skin and intestines, and in some parenchymal organs,
notably the liver.

CELL PROLIFERATION: SIGNALS AND CONTROL
MECHANISMS
These include the
REMNANTS OF THE INJURED TISSUE (which attempt to restore
normal structure),
VASCULAR ENDOTHELIAL CELLS (to create new vessels that
provide the nutrients needed for the repair process), and
FIBROBLASTS (the source of the fibrous issue that forms the scar
to fill defects that cannot be corrected by regeneration

The ability of tissues to repair themselves is determined,
in part, by their intrinsic proliferative capacity. the tissues
of the body are divided into three groups.
• Labile (continuously dividing) tissues
• Stable tissues
• Permanent tissues.

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
connective tissue synthesis and deposition.

Repair begins within 24 hours of injury by the emigration of
fibroblasts and the induction of fibroblast and endothelial cell
proliferation.
By 3 to 5 days, the specialized granulation tissue that is
characteristic of healing is apparent.

FORMATION OF GRANULATION TISSUE AND THE
SCAR.
Angiogenesis is the process of new blood vessel
development from existing vessels. It is critical in
healing at sites of injury, in the development of collateral
circulations at sites of ischemia,
Angiogenesis involves sprouting of new vessels from
existing ones, and consists of the following steps

GROWTH FACTORS.
1)Vascular endothelial growth factors
(VEGFs), mainly VEGF-A stimulates both migration and
proliferation of endothelial cells, thus initiating the
process of capillary sprouting in angiogenesis. It
promotes vasodilation by stimulating the production of
NO and contributes to the formation of the vascular
lumen.

2) FIBROBLAST GROWTH FACTORS (FGFS),
Mainly FGF-2, stimulates the proliferation of
endothelial cells. It also promotes the
migration of macrophages and fibroblasts to
the damaged area, and stimulates epithelial
cell migration to cover epidermal wounds.

3) ANGIOPOIETINS
1 and 2 (Ang 1 and Ang 2 structural maturation of new vessels)
are growth factors that play a role in angiogenesis and the.
Newly formed vessels need to be stabilized by the recruitment of
pericytes and smooth muscle cells and by the deposition of
connective tissue.

4) Notch signaling.
Through “cross-talk” with VEGF, the Notch signaling
pathway regulates the sprouting and branching of new
vessels and thus ensures that the new vessels that are
formed have the proper spacing to effectively supply
healing tissue with blood.

5) ECM proteins
participate in the process of vessel sprouting in
angiogenesis, largely through interactions with integrin
receptors in endothelial cells and by providing the
for vessel growth.
6) Enzymes in the ECM, notably the matrix
metalloproteinases (MMPs), degrade the ECM to permit
remodeling and extension of the vascular tube.

DEPOSITION OF CONNECTIVE TISSUE
The laying down of connective tissue occurs in two steps:
 (1) migration and proliferation of fibroblasts into the site
of injury
 (2) deposition of ECM proteins produced by these cells

These processes are under influence by locally produced
cytokines and growth factors, including
PDGF,FGF-2, and TGF-β.
The major sources of these factors are inflammatory cells,
particularly alternatively activated (M2) macrophages, which
are present at sites of injury and in granulation tissue.

Transforming growth factor-β (TGF-β) is the most
important cytokine for the synthesis and deposition of
connective tissue proteins.
TGF-β stimulates fibroblast migration and proliferation,
increased synthesis of collagen and fibronectin, and
decreased degradation of ECM due to inhibition of
metalloproteinase

HEALING BY FIRST INTENTION
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
clean, uninfected surgical incision approximated by
surgical sutures

The repair consists of three connected processes:
Inflammation,
Proliferation of epithelial and other cells,
Maturation of the connective tissue scar.

STEPS OF HEALING
 Activation coagulation pathways,
 Formation of a blood clot on the wound surface entrapped red cells, the
clot contains fibrin, fibronectin, and complement proteins.
 The clot serves to stop bleeding and acts as a scaffold for migrating cells,
which are attracted by growth factors, cytokines, and chemokines released
into the area.
 Release of VEGF leads to increased vessel permeability and edema.
 As dehydration occurs at the external surface of the clot, a scab covering
the wound is formed.

WITHIN 24 HOURS,
neutrophils are seen at the incision margin, migrating toward the
fibrin clot. They release proteolytic enzymes that begin to clear
the debris.
Basal cells at the cut edge of the epidermis begin to show
increased mitotic activity.
Within 24 to 48 hours,
Epithelial cells from both edges have begun to migrate and
proliferate along the dermis, depositing basement membrane
components as they progress. The cells meet in the midline
beneath the surface scab, yielding a thin but continuous
epithelial layer that closes the wound.

BY DAY 3,
Neutrophils replaced by macrophages,
Macrophages clearing extracellular debris, fibrin, and other
foreign material, and promoting angiogenesis and ECM
deposition.
Collagen fibers are now evident at the incision margins.
Epithelial cell proliferation continues, forming a covering.

BY DAY 5,
 Neovascularization as granulation tissue fills the incisional space.
 These new vessels are leaky, allowing the passage of plasma
proteins and fluid into the extravascular space.
 Thus, new granulation tissue is often edematous.
 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, and FGF, and the cytokines IL-
1 and TNF.

DURING THE SECOND WEEK,
There is continued collagen accumulation and fibroblast
proliferation . The leukocyte infiltrate, edema, and increased
vascularity are substantially diminished.

BY THE END OF THE FIRST MONTH,
The scar comprises a cellular connective tissue largely
devoid of inflammatory cells and covered by an
essentially normal epidermis.

HEALING BY SECOND 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 this inflammation is more intense there is abundant
granulation tissue formation, accumulation of ECM and
formation of large scar.
In wound large tissue deficit ,clot is large ,more exudate ,more
necrotic debris.
More macrophage came to remove debries
Large granulation tissue need for fill the gap

1st matrix contain fibrin ,plasma fibronectin, and type 3
collagen
Ultimately granulation tissue converted into pale ,avascular
scar, composed of spindle shape fibroblast ,dense collagen
fragment of elastic tissue .

At the end of 1month
Epidermis recover to normal thickness
The scar is acellular and avascular connective tissue
devoid of inflammation.
Wound contraction usually occur in large wound.
It is a important feature of secondary union

With in 6 month wound reduced to 5-10%

FIBROSIS
The term fibrosis is most often used to describe the
extensive deposition of collagen that occurs in the lungs,
liver, kidney, and other organs as a consequence of
chronic inflammation, or in the myocardium after
extensive ischemic necrosis (infarction).
 If fibrosis develops in a tissue space occupied by an
inflammatory exudate, it is called organization

Difference between 1˚ & 2˚ union of wound
FEATURES PRIMARY SECONDARY
CLEANLINESS CLAEN NOT CLEAN
INFECTION NOT INFECTED INFECTED
MARGINS SURGICALLY CLEAN IRREGULAR
SUTURES USED NOT USED
HEALING SMALL GRANULATION TISSUE LARGE GRANULATION TISSUE
OUT COME LINEAR SCAR IRREGULAR WOUND
COMPICATION NOT FRQUENT FREQUENT

Healing

More Related Content

What's hot

Similar to Healing

Recently uploaded

Healing