HEALING
Healing is the body response to injury in an attempt to restore normal structure and function.
Healing involves 2 distinct processes:
Regeneration when healing takes place by proliferation of parenchymalcells and usually results in
complete restorationof the original tissues.
> Repair when healing takes place by proliferation of connective tissue elements resulting in fibrosis and
scarring. At times, both the processes take place simultaneously.
REGENERATION
Some parenchymal cells are short-lived while others have a longer lifespan. In order to maintain proper
structure of tissues, these cells are under the constant regulatory control of their cell cycle. These
include growth factors such as: epidermal growth factor, fibroblast growth factor, plateletderived
growth factor, endothelial growth factor, transforming growth factor-ß.
Depending upon their capacity to divide, the cells of the body can be divided into 3 groups: labile cells,
stable cells, and permanent cells.
1. Labile cells---- These cells continue to multiply throughout life under normal physiologic conditions. These
include: surface epithelial cells of the epidermis, alimentary tract, respiratory tract, urinary tract, vagina,
cervix, uterine endometrium, haematopoietic cells of bone marrow and cells of lymph nodes and spleen.
, 2. Stablecells,---These cellsdecrease or lose their ability to
proliferate after adolescence butretain the
cells oforgans
capacity to multiply in response to stimulithroughout adult life. These include: parenchymal fibroblasts.
muscle cells,
Iike liver, pancreas, kidneys, adrenal and thyroid; mesenchymal cells like smooth
vascular endothelium, bone and cartilage cells.
include:
3. Permanent cells. These cells lose their abilityto proliferate around the time of birth. These
neurons of nervous system, skeletal muscle and cardiac musclecells.
> Regeneration of any type of parcnchymal cells involves the following 2 processes:
i) Proliferation of original cells from the margin of injury with migration so as to cover the gap.
ii) Proliferation of migrated cells with subsequent differentiation and maturation so as to reconstitute the
originaltissue.
REPAIR--Repair is the replacement of injured tissue by fibrous tissue.
Twoprocesses are involved in repair:
1. Granulation tissue formation; and
2. Contraction of wounds.
Granulation Tissue Formation
The term granulation tissue derives its name from slightly granular and pink appearance of the tissue.
Each granule corresponds histologically to proliferation of new small bloodvessels which are slightly
lifted on the surface by thin covering of fibroblasts and young collagen.
The following 3 phases are observed in the formation of granulation tissue
1.Phase of inflammation.
Following trauma, blood clots at the site of injurý there is acute inflammatory response with exudation
of plasma, neutrophils and some monocytes within 24 hours.
2. Phase of clearance.
Combination of proteolytic enzymes liberated from neutrophils, autolyticenzymes from dead tissues
cells, and phagocyticactivity of macrophages clear off the necrotic tissue, debris and red blood cells.
3.Phase of ingrowth of granulation tissue.
> This phase consists of 2 main processes: angiogenesis or neovascularisation, and fibrogenesis.
i) Angiogenesis (neovascularisation). Formation of new blood vessels at the site of injury takes place by
proliferation of endothelial cells from the margins of severed blood vessels. Initially, the proliferated
endothelial cells are solid buds but within few hours develop a lumen and start carrying blood. The newly
formed blood vessels are more leaky, accounting for the oedenmatous appearance of new granulation tissue.
Soon, these blood vessels differentiate into muscular arterioles,thin-walled venules and true capillaries.
The process of angiogenesis is stimulated with proteolytic destruction of basement membrane. Angiogenesis
takes place under the influence of following factors:
a) Vascular endothelial growth factor (VEGF)elaborated by mesenchymal cells while its receptors are present
in endothelial cells only.
b) Platelet-derived growth factor (PDGF), transforming growth factor-ß (TGF-P), basic fibroblast growth
factor (bFGF) and surface integrins are allassociated with cellular proliferation.
ii) Fibrogenesis. The newly formed blood vessels are present in an amorphous ground substance or matrix.
The new fibroblasts originate from fibrocytes as well as by mitotic division of fibroblasts. Some of these
fibroblasts have combination of morphologic and functional characteristics of smooth muscle cells
(myoftbroblasts), Collagen fibrils begin to appear by about 6th day. As maturation proceeds, more and more of
collagen is formed while the number of active fibroblasts and new blood vessels decreases. This results in
formation of inactive looking scar known as cicatrisation.
Healing is the body response to injury in an attempt to restore normal structure and function.
Healing involves 2 distinct processes:
Regeneration when healing takes place by proliferation of parenchymalcells and usually results in
complete restorationof the original tissues.
> Repair when healing takes place by proliferation of connective tissue elements resulting in fibrosis and
scarring. At times, both the processes take place simultaneously.
REGENERATION
Some parenchymal cells are short-lived while others have a longer lifespan. In order to maintain proper
structure of tissues, these cells are under the constant regulatory control of their cell cycle. These
include growth factors such as: epidermal growth factor, fibroblast growth factor, plateletderived
growth factor, endothelial growth factor, transforming growth factor-ß.
Depending upon their capacity to divide, the cells of the body can be divided into 3 groups: labile cells,
stable cells, and permanent cells.
1. Labile cells---- These cells continue to multiply throughout life under normal physiologic conditions. These
include: surface epithelial cells of the epidermis, alimentary tract, respiratory tract, urinary tract, vagina,
cervix, uterine endometrium, haematopoietic cells of bone marrow and cells of lymph nodes and spleen.
, 2. Stablecells,---These cellsdecrease or lose their ability to
proliferate after adolescence butretain the
cells oforgans
capacity to multiply in response to stimulithroughout adult life. These include: parenchymal fibroblasts.
muscle cells,
Iike liver, pancreas, kidneys, adrenal and thyroid; mesenchymal cells like smooth
vascular endothelium, bone and cartilage cells.
include:
3. Permanent cells. These cells lose their abilityto proliferate around the time of birth. These
neurons of nervous system, skeletal muscle and cardiac musclecells.
> Regeneration of any type of parcnchymal cells involves the following 2 processes:
i) Proliferation of original cells from the margin of injury with migration so as to cover the gap.
ii) Proliferation of migrated cells with subsequent differentiation and maturation so as to reconstitute the
originaltissue.
REPAIR--Repair is the replacement of injured tissue by fibrous tissue.
Twoprocesses are involved in repair:
1. Granulation tissue formation; and
2. Contraction of wounds.
Granulation Tissue Formation
The term granulation tissue derives its name from slightly granular and pink appearance of the tissue.
Each granule corresponds histologically to proliferation of new small bloodvessels which are slightly
lifted on the surface by thin covering of fibroblasts and young collagen.
The following 3 phases are observed in the formation of granulation tissue
1.Phase of inflammation.
Following trauma, blood clots at the site of injurý there is acute inflammatory response with exudation
of plasma, neutrophils and some monocytes within 24 hours.
2. Phase of clearance.
Combination of proteolytic enzymes liberated from neutrophils, autolyticenzymes from dead tissues
cells, and phagocyticactivity of macrophages clear off the necrotic tissue, debris and red blood cells.
3.Phase of ingrowth of granulation tissue.
> This phase consists of 2 main processes: angiogenesis or neovascularisation, and fibrogenesis.
i) Angiogenesis (neovascularisation). Formation of new blood vessels at the site of injury takes place by
proliferation of endothelial cells from the margins of severed blood vessels. Initially, the proliferated
endothelial cells are solid buds but within few hours develop a lumen and start carrying blood. The newly
formed blood vessels are more leaky, accounting for the oedenmatous appearance of new granulation tissue.
Soon, these blood vessels differentiate into muscular arterioles,thin-walled venules and true capillaries.
The process of angiogenesis is stimulated with proteolytic destruction of basement membrane. Angiogenesis
takes place under the influence of following factors:
a) Vascular endothelial growth factor (VEGF)elaborated by mesenchymal cells while its receptors are present
in endothelial cells only.
b) Platelet-derived growth factor (PDGF), transforming growth factor-ß (TGF-P), basic fibroblast growth
factor (bFGF) and surface integrins are allassociated with cellular proliferation.
ii) Fibrogenesis. The newly formed blood vessels are present in an amorphous ground substance or matrix.
The new fibroblasts originate from fibrocytes as well as by mitotic division of fibroblasts. Some of these
fibroblasts have combination of morphologic and functional characteristics of smooth muscle cells
(myoftbroblasts), Collagen fibrils begin to appear by about 6th day. As maturation proceeds, more and more of
collagen is formed while the number of active fibroblasts and new blood vessels decreases. This results in
formation of inactive looking scar known as cicatrisation.
