Prolotherapy is the iatrogenic stimulation of the wound healing and tissue repair process.
Healing and repair
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Transcript of Healing and repair
Healing and repair - 1Healing and repair - 1
Dr H.M.D.MoratuwagamaDr H.M.D.MoratuwagamaDept of PathologyDept of Pathology
Faculty of mrdicine-RagamaFaculty of mrdicine-Ragama
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 present1)Labile cells Regenerate regularly Surface epithelial cells Surface epithelium of the GIT , Skin2)Stable cells Normally slowly regenerate Divide when necessary eg. Hepatocytes3)Permanent cells No effective regeneration eg. Neural cells of CNS, cardiac muscle
Definitions
RegenerationGrowth of cells to replace the lost structure ex: skin,haemopoietic system,GIT HealingTissue response 1.wound 2.Inflammatory process 3.cell necrosisTwo processes-Regeneration Scar formation-laying down of fibrous tissue
Tissue injury
Total
Scar
Partial
Labile cells
Stable cellsPermanant
RegenerateRegenerate/scar Scar
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 tissue2)Proliferation and migration of parenchymal
and connective tissue cells3)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 by1) Increase collagen deposition2) Cross linking of collagen fibers3) Change of collagen fibers from type 3 to type 1
Cutaneous wound healing1)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 thickens2nd Week Accumulation of collagen and fibroblast
proliferation Regression of vascular channels,
inflammation and oedema4th Week Scar Covered by epidermis Dermal appendages are absent Wound strength - over several months
Differences from primary union
1) Larger fibrin clot2) More necrotic debris and exudate3) Intense inflammatory reaction4) Abundant granulation tissue5) 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 2nd to 3rd month 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 healingcont.
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
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