Wound Healing & Repair

Acute inflammation

 A rapid, non-specific response to cellular injury

 Orchestrated by cytokines released from injured cells, e.g histamine, serotonin, prostaglandins,

leukotrienes, and platelet-activating factor

 Cytokines activate endothelial cells,

 leading to the formation of an acute inflammatory exudate containing fluid, fibrin, and neutrophils
• Severe acute inflammation may lead to a localized collection of pus

within a necrotic cavity ( abscess )

• Acute inflammation may resolve, heal with scarring, or progress to

chronic inflammation
Chronic inflammation

 Persistent form of inflammation in which there is simultaneous tissue damage and attempted repair

 May arise from acute inflammation or occur from the outset

 Characterized by the presence of chronic inflammatory cells, namely macrophages, lymphocytes, and
plasma cells

 More likely to heal with irreversible scarring than resolve

Granulomatous inflammation

 A special type of chronic inflammation characterized by the presence of activated macrophages known as
epithelioid histiocytes

 Collections of epithelioid macrophages are known as granulomas

 Granulomatous inflammation is associated with foreign bodies, persistent infections (e.g mycobacteria), and
diseases whose cause is unclear (e.g sarcoidosis)
Healing

 Process of replacing dead and damaged tissue with healthy tissue

 May occur through regeneration or repair
Regeneration

 Resolution or replaces damaged cells with the same type of cell and is the ideal outcome
 This can only occur if the connective tissue framework of the tissue is not disrupted and if the tissue is
capable of regeneration
Repair

 Begins with the formation of granulation tissue which is then converted into a collagen-rich scar. Although
the structural integrity is maintained, there is loss of function of the tissue that is scarred
 Tissue injury

Partial
Total

Labile cells
Permanant
Stable cells

Scar

Regenerate/scar Scar
Regenerate
According to the potential of cell renewal 3 types of cells
are present

1)Labile cells
Regenerate regularly
Surface epithelial cells
Surface epithelium of the GIT , Skin
2)Stable cells
Normally slowly regenerate
Divide when necessary
e.g Hepatocytes
3)Permanent cells
No effective regeneration
e.g Neural cells of CNS, cardiac muscle
Scar formation occurs when

1)Damage to permanent cells

2)Severe destruction of connective tissue framework

3)With extensive cell injury

4)In chronic inflammation

Steps in repair by scar tissue formation

1)Inflammatory response

Polymorphs and macrophages

Remove damaged and dead tissue

2)Proliferation and migration of parenchymal and connective tissue cells

3)Formation of new blood vessels (angiogenesis) and granulation tissue

4. Synthesis of ECM proteins and collagen deposition

5. Tissue remodeling

6. Wound contraction

7. Wound strength
Angiogenesis

Formation of blood vessels from existing blood vessels from

A) Endothelial precursor cells in BM

B) From pre-existing vessels

 Growth factors involved in angiogenesis

1)Formation of new vessels

 VEGF (Vascular endothelial growth factor)

 FGF (Fibroblast growth factors)

2)Stability of new vessels

 Angiopoietin 1 & 2 - Peri endothelial cells

 PDGF (Platelet-derived growth factor is one among numerous growth factors that regulate cell

growth and division) - Smooth muscle cells

 TGF – beta ( Transforming growth factor beta is a multifunctional cytokine belonging to the
 VEGF - Vascular endothelial growth factor (Angiogenesis )

increased vascular permeability

 Exudation and deposition of plasma proteins

 Provides a stroma for the proliferating endothelial cells and fibroblasts

 Wound healing

1)Healing by first intension (Primary union) wounds with opposed edges

When a wound involves minimal or no tissue loss and has edges that are well
approximated (closed), primary(first) intention healing takes place. Little
scarring expected. Clean surgical incision heals by this method.
 2)Healing by second intension (Secondary union)

 Wounds with separated edges

 Healing occurs when a wound (1) involves extensive tissue loss, which prevents wound edges from
approximating, or (2) should not be closed - because it is infected. Wound is left open, heals from the
inner layer to the surface by filling in with beefy red granulation tissue. (pressure ulcers and infected
wounds)
Primary wound healing
Secondary Wound Healing
 Healing process

Within 24 hrs- Neutrophils enter

24-48hrs
• Epithelial cells move and fuse in the midline
Day 3
• Macrophages move in
• Granulation tissue forms
• Collagen laid down
• epithelial cell layer forms
Day 5
• Granuation tissue fills the gap
• Maximal neovascularization
• Collagen fibrils increases
• Epithelial cells thickens
2nd Week
• Accumulation of collagen and fibroblast proliferation
• Regression of vascular channels, inflammation and oedema
4th Week
• Scar
• Covered by epidermis
• Dermal appendages are absent
• Wound strength - over several months
Factors that retard wound healing

 Local factors
• Poor blood supply - arteriosclerosis, venous abnormalities(ex: varicose
veins)
• Denervation
• Local infection
• Foreign bodies – interfere with healing and cause infection
• Presence of a haematoma
• Mechanical stress
Systemic factors that delay wound healing

Anaemia

Drugs-Steroids ( anti-inflammatory) , cytotoxic drugs

Genetic disorders with collagen defects Ehlers – Danlos syndrome

Osteogenesis imperfecta

Marfans syndrome

Diabetes

Malignancy
• Nutritional deficiencies

• Systemic infection

• Trauma , hypovolaemia , hypoxia

Other factors that influence wound healing

• Age
• Size
• Location
• Mechanical factors
Summary

 The process by which healing occurs in a tissue is dependant on

several factors– Type of cell , extent of injury etc
 Depending on the type of wounds, healing process follows two
pathways
 Healing by primary intension
 Healing by second intension
 There are systemic and local factors that may delay wound healing
Thank you