Healing and repair

Presented by: Mahnoor Zafar

Roll NO: 86
Objectives

• Describe the steps of cutaneous

wound healing by primary intension
and secondary intension

• List the factors which delay wound

healing
• Describe the process of healing in
specialized tissues
• 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
eg. Hepatocytes
3)Permanent cells
No effective regeneration
eg. Neural cells of CNS, cardiac muscle
Definitions

 Regeneration
Growth of cells to replace the lost structure
ex: skin,haemopoietic system,GIT
 Healing

Tissue response 1.wound

2.Inflammatory process
3.cell necrosis
Two processes-Regeneration
Scar formation-laying down of fibrous tissue
 Tissue injury

Partial
Total

Labile cells
Permanant
Stable cells

Scar

Regenerate/scar Scar
Regenerate
Scar formation occurs when

1)Damage to permanent cells

2)Severe destruction of connective

tissue frame work

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
Steps in repair by scar tissue formation
cont.

4) Synthesis of ECM proteins and collagen

deposition

5) Tissue remodeling

6) Wound contraction

7) Wound strength
What is angiogenesis?
Formation of blood vessels from existing blood
vessels

From
 A) Endothelial precursor cells in BM

 B) From pre-existing vessels

 What is granulation tissue?
 Highly vascularized connective tissue
 Composed of –
Newly formed capillaries
Proliferating fibroblasts
Inflammatory cells in oedematous stroma
 Macro –
Pink granular
Soft and fleshy
 new capillaries (result of proliferation of endothelial cells
- angiogenesis or neovascularization) in an edematous
atmosphere of fibroblasts (spindle shaped), myofibroblasts,
mononuclear inflammatory cells, macrophages, neutrophils,
Growth factors involved in
angiogenesis
1)Formation of new vessels
VEGF
FGF
2)Stability of new vessels
Angiopoietin 1 & 2 - Periendothelial
cells
PDGF - Smooth muscle
cells
TGF – beta - ECM protein
secretion
ECM protein production (Initial)
 VEGF - (Angiogenesis and )
increased vascular permeability

Exudation and deposition of

plasma proteins
Provides a stroma for the
proliferating endothelial cells
and fibroblasts
ECM protein production
Fibroblasts migration

Macrophages , platelets , endothelium

Growth factors Cytokines

TGF – beta TNF , IL -1
PDGF
FGF

Fibroblast migration and proliferation

ECM deposition and scar formation
 Growth factors (PDGF , FGF , TGF) &
Cytokines (IL-1 & IL-13)

 Stimulate fibroblast to produce collagen

 Net collagen is dependant on both the

production and degradation
Tissue remodeling
 Degradation of collagen and other ECM
proteins by a family of matrix
metalloprotinases (MMPs)
 TIMs –(Tissue inhibitors of
metaloprotinases) inhibit their action

 Net result is the formation of an

avascular firm white scar tissue
Wound contraction
 By the contraction of a specialized cell in the
granulation tissue called myofibroblasts

 Wound defect decreased in size

 Harmful effect – Stenosis , contractures

Wound strength
It is acquired by
1) Increase collagen deposition
2) Cross linking of collagen fibers
3) Change of collagen fibers from type 3 to
type 1
Cutaneous wound healing
1)Inflammation
 Early and late

2)Granulation tissue
formation and
re-epithelialization

3)Wound contraction
ECM deposition and
remodeling
Wound healing

1)Healing by first intension

(Primary union)
 -wounds with opposed edges-
2)Healing by second intension
(Secondary union)
 -Wounds with separated edges-
 Healing by first intension
(Primary union)
 In –Surgically incised
Clean and uninfected
Limited death of
epithelial cells and
connective tissue
Edges approximated
by surgical sutures
Healing by second intension
Wounds with
 Extensive cell
death
 Large defects +/-
infection
 Wounds not
approximated by
sutures
Healing by primary intension
 Surgical wounds

 Gap filled by clotted blood containing fibrin

and blood cells
 Scab forms
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

2n Week
 Accumulation of collagen and fibroblast
d

proliferation
 Regression of vascular channels,
inflammation and oedema
4t Week
h
Scar

Covered by epidermis

Dermal appendages are absent

Wound strength - over several months
Differences from primary union

1) Larger fibrin clot

2) More necrotic debris and exudate
3) Intense inflammatory reaction
4) Abundant granulation tissue
5) Wound contraction (by myofibroblasts)
6) Scar formation and thinning of
epidermis
Primary wound healing
Secondary Wound Healing
Secondary Wound Healing
Secondary Wound Healing
Wound strength
 Day 7
10% of the original tissue
 2n to 3r month
d d
70-80% of original tissue
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
 Presence of a necrotic tissue
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
Systemic factors that delay wound healing
cont.
 Nutritional deficiencies –
eg- Protein, Vitamin C, Zinc
 Systemic infection
 Trauma , hypovolaemia , hypoxia
 Uraemia
 Haematological abnormalities – Defect of
neutrophil function
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