pathology lecture

1. Healing and repair - 1
Dr H.M.D.Moratuwagama
Dept of Pathology
Faculty of mrdicine-Ragama

2. 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

3. 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


4. 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

5. Tissue injury
Partial
Total
Labile cells
Stable cells
Permanant
Scar
Regenerate
Regenerate/scar
Scar

6. 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

7. 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

8. 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

9. What is angiogenesis?
Formation of blood vessels from existing blood
vessels
From
 A) Endothelial precursor cells in BM
 B) From pre-existing vessels

10. 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

11. 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,

12. 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

13. 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

14. ECM protein production
Fibroblasts migration
 Macrophages
Growth factors
 TGF – beta
 PDGF
 FGF
, platelets , endothelium
Cytokines
TNF , IL -1
Fibroblast migration and
proliferation

15. ECM deposition and scar formation
 Growth
factors (PDGF , FGF , TGF) &
Cytokines (IL-1 & IL-13)
 Stimulate
 Net
fibroblast to produce collagen
collagen is dependant on both the
production and degradation

16. 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

17. Wound contraction

By the contraction of a specialized cell in the
granulation tissue called myofibroblasts

Wound defect decreased in size

Harmful effect – Stenosis , contractures

18. 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

20. Cutaneous wound healing
1)Inflammation
 Early and late
2)Granulation tissue
formation and
re-epithelialization
3)Wound contraction
ECM deposition and
remodeling

21. Wound healing
1)Healing by first intension
(Primary union)
 -wounds with opposed edges2)Healing by second intension
(Secondary union)
 -Wounds with separated edges-

22. 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

23. Healing by second intension
Wounds with
 Extensive cell
death
 Large defects +/infection
 Wounds not
approximated by
sutures

24. Healing by primary intension
 Surgical
 Gap
wounds
filled by clotted blood containing fibrin
and blood cells
 Scab forms

25. 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

26. 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

29. 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

30. Primary wound healing

31. Secondary Wound Healing

32. Secondary Wound Healing

33. Secondary Wound Healing

34. Wound strength
 Day
7
10% of the original tissue
 2nd to 3rd month
70-80% of original tissue

35. 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


36. 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

37. 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

38. Other factors that influence wound
healing
 Age
 Size
 Location
 Mechanical
factors

39. 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

40. THANK YOU