Healing and Repair
R obbin pathology 1 0th ed
PROF. DR SOFIA KHAN
(MBBS,FCPS, MHPE)
PATHOLOGY
Learning Objectives
• Define wound and its types
• Define healing and repair
• Describe angiogenesis
• Describe Granulation tissue
• Factors involve in wound healing
• Phases of cutaneous wound healing
• Types of healing
• Complications of healing
What is a Wound?
A break in the integrity of skin or tissue
Which may be associated with disruption of the
structure and function
A cut or break in the continuity of any tissue caused
by injury or operation/surgery
Types of Wounds ?
Lacerated
wounds
Clean
Penetrating incised
wounds wound
Hematoma Abrasion
Crush injury
Healing ?
Restoration of tissue architecture and function
after the injury
A reparative tissue response to a wound,
inflammation or necrosis, often leads to fibrosis
Consist of two process
Regeneration
Repair
Regeneration
• Perfect restoration
• No scar formation
• Complete restitution of lost
and damage tissue
• Growth of cells to replace lost
tissues
• The goal of surgical
procedures is regeneration
Regeneration
Tissues with high proliferative capacity,
The hematopoietic system
The epithelia of the skin
The epithelia of gastrointestinal (GI) Tract
Renew themselves continuously and can
regenerate after injury, as long as the stem cells of
these tissues are not destroyed.
Repair
• Ability to restore normal
function and structure
• Repair may restore some
original structures but can
cause structural
derangements
• Results in the formation of
scar tissue
• When tissue injury is severe and chronic, it results in
damage of both parenchymal cells and the stromal
tissue, healing can not be accomplished by
regeneration.
• In these conditions, the main healing process is
repair by deposition of collagen and other ECM
components, causing the formation of a scar.
In contrast to regeneration which involves the restitution
of tissue components,
repair is a fibroproliferative response
that “patches” rather than restores the tissue.
If the damage persists, inflammation becomes chronic,
leading to
an excess deposition of connective tissue known as
Fibrosis.
• In most healing processes, a combination of repair and
regeneration occurs.
• The relative contributions of repair and regeneration are
influenced by:
The proliferative capacity of the cells of the tissue
the integrity of the extracellular matrix
The resolution or chronicity of the injury and inflammation.
Angiogenesis
Angiogenesis is the process of new blood vessel
formation from existing vessels.
• Clinical importance:
• Repair post-inflammation
• Formation collateral circulation (post-MI)
• Support growth of neoplasms
1. Vasodilation in response to nitric oxide and increased permeability
induced by vascular endothelial growth factor (VEGF).
2. Separation of pericytes from the abluminal surface and breakdown of
the basement membrane to allow formation of a vessel sprout.
3. Migration of endothelial cells toward the area of tissue injury FGF-2
4. Proliferation of endothelial cells just behind the leading front (“tip”) of
migrating cells.
5. Remodeling into capillary tubes.
6. Recruitment of periendothelial cells (pericytes for small capillaries and
smooth muscle cells for larger vessels) to form the mature vessel.
7. Suppression of endothelial proliferation and migration and deposition
of the basement membrane
Mechanisms of Angiogenesis
Angiogenesis is a fundamental process that affects physiologic reactions
Wound healing
Regeneration
Vascularization of ischemic tissues
Menstruation
Pathologic processes
Tumor development and metastasis
Diabetic retinopathy
Chronic inflammation
Granulation Tissue
Fibroblasts and vascular endothelial cells proliferate in the first
. to 72 hours of the repair process to form a specialized type of
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tissue called granulation tissue,
which is a hallmark of tissue repair
its pink, soft, granular appearance on the surface of wounds
presence of new small blood vessels and the proliferation of fibroblasts
new granulation tissue is often edematous.
VEGF
most important growth factor in adult tissues
undergoing physiologic angiogenesis
(e.g., proliferating endometrium) as well as
pathological angiogenesis
STABILIZATION
Angiopoietins 1 and 2 , PDGF,
and TGF-β participate in the
stabilization process.
Growth Factors and Cytokines Affecting Various
Steps in Wound Healing
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
Phases of cutaneous wound healing
Feature Primary intension Secondary intension
Wound type Surgical incised Lacerated , contaminated
wound
Cleanliness of wound Clean Unclean
Infection Uninfected May be infected
Margins Clean Irregular
Sutures Used Not used
Healing Scanty granulation tissue Exuberant granulation tissue
Outcome Neat linear scar Contracted irregular wound
Complications Infrequent Suppuration ,may require
debridement
ABNORMALITIES IN TISSUE REPAIR
COMPLICATIONS OF WOUND
HEALING
Infection
Dehiscence
Incisional hernia
Contractures
Hypertrophic scar
Keloid formation
Exuberant granulation
infection
Dehiscence
Incisional hernia
(claw-oid) /claw -like
Keloid
are raised scars that grow
beyond the borders of the
original wound
Excess production of collagen 2
are raised scars that is localized
to wound.
Hypertrophic scar
contractures
Exuberant
granulation