vascular changes in inflamation
TRANSCRIPT
Vascular changes of inflammation
Introduction
Julius Cohnheim (1839-1884) was the first todescribe vascular changes in 1877 by spreadingthe mesentery of a frog and observed the flow ofblood through the vessels, following theapplication of a drop of dilute acetic acid
The vascular changes are:
1. Change in blood vesselsi. Momentary vasoconstriction
ii. Vasodilatation
2. Change in the rate of blood flowi. Increased vascular permeability
ii. Slowing of the circulation
iii. Stasis
3. Change in the blood stream
4. Exudation of plasma
5. Emigration of luecocytes
6. Diapedesis of erythrocytes
1.Changes in the blood vessels
i. Momentary vasoconstriction:
Immediately upon application of the
Irritant, the arterioles are constricted
Constriction is very short lived and
trnasient and not much of significance
It is possible due to action chemical
mediators or neurogenic
II. Vasodilatation
Momentry constriction is quickly follwed by
vasodilatation of vessels which first involves
arterioles & then results in opening of new
microvascular beds in the area
Normally the numbers of capillaries which remain
dormant or collapsed are opened up
The opening of new vascular beds results in
increased vascularity of the area.
Dilation is caused by the action of chemical substances
released locally. These substances are known as chemical
mediators of inflammation.
Vasodilation leads to hyperaemia and increased blood
flow, the cause of heat and redness.
2. Changes in the Rate of Flow
The early vasodilation results in increased blood flow
This is soon followed by slowing of the circulationwhich is brought about by increased permeability ofthe microvasculature (venules, small veins, andcapillaries), and leads to the outpouring of protein richfluid into the extravascular tissues
This results in concentration of red cells in smallvessels and increased viscosity of the blood
In tissue sections, this is seen as dilated small vesselspacked with red cells - a condition termed stasis.
i. Increased vascular permeability
In acute inflammation there is striking increase in
permeability of the vessels to proteins
The loss of protein from plasma reduces the
intravascular osmotic pressure and increase osmotic
pressure of interstitial fluid
This further cause marked out flow of fluid and its
accumulation in the interstitial / extravascular tissue
The net increase of extravascular fluid is called
inflammatory oedema.
Mechanisms of Increased Vascular Permeability
A. Formation of endothelial gaps in venules:
Normally, the endothelial cells of blood vessels are fused by
tight intercellular junctions
In inflammation, these are loosened to permit outflow of fluid
and protein
Most chemical mediators of inflammation cause an increase
in vascular permeability by opening inter-endothelial
junctions
The inter-endothelial gaps are produced by contraction of
endothelial cells, which results in widening of the junction.
Cont… This is the most common mechanism of vascular leakage,
and is produced by histamine, bradykinin, leukotrienes, and
many other types of chemical mediators
There for it is called the 'immediate transient response‘
This type of leakage affects only venules (20 to 60 mm in
diameter); endothelium in capillaries and arterioles is
unaffected. This is due to a greater density of receptors
B. Endothelial cell retraction:
There is a structural reorganization of the endothelial
cytoskeleton. As a result cells retract (draw back) from each
other, there is formation of endothelial gaps
Cytokine mediators induce endothelial cell retraction.
Endothelial retraction takes 4-6 hours to develop and
persists for 24 hours or more
C. Direct endothelial injury:
This vascular leakage due to endothelial cell necrosis and
detachment. It is usually seen after severe injuries (burns or
infections)
Leakage begins immediately after injury and persists for
several hours (or days) until the damaged vessels are
thrombosed or repaired
The reaction is known as the immediate sustained response
Venules, capillaries, and arterioles can all be affected
D. Delayed prolonged leakage:
Starts after hours and last for several days
Seen in venules and capillaries thermal injury, x-ray
or ultraviolet radiation & bacterial toxins
E. Leukocyte-dependent endothelial injury:
leukocyte accumulation during inflammation release
toxic oxygen species and proteolytic enzymes that cause
endothelial injury and detachment - resulting in
increased vascular permeability.
This form of injury seen in those vascular sites (venules
and pulmonary capillaries) where leukocytes can adhere
to the endothelium.
F. Increased transcytosis:
Transcytosis occurs across channels formed by fusion of uncoated vesicles
Certain mediators, e.g., vascular endothelial growth factor (VEGF) cause increased transcytosis
G. Leakage from new blood vessels:
Tissue repair involves new blood vessel formation
(angiogenesis)
New vessel sprouts remain leaky until endothelial cells
differentiate and form intercellular junctions
Estimation of Increased Vascular Permeability
• Increased vascular permeability can be
demonstrated or quantitated, experimentally, in
several ways:
(1) Dye technique
(macroscopic method)
(2) Colloidal carbon technique
(microscopic method)
1) Dye technique (macroscopic method)
A vital dye such as Evans blue or pontamine sky blue is
injected into the blood where it bound to serum albumin
Wherever there is a leak, the dye-albumin complex
comes out and forms a blue patch indicating an increase
in vascular permeability
Increased vascular permeability then be assessed by
measuring size of the blue patch and the intensity of its
colour
Exuded dye can be extracted chemically and measured
spectrophotometrically
Thus, an increase in vascular permeability can be
quantitated.
It does not identify the leaky vessels
2. Colloidal carbon technique
Colloidal carbon technique, in contrast, identifies the
particular vessels through which the protein has been
leaking during inflammation
A colloidal suspension of carbon, which contains
particles 25-30 nm in diameter, is injected intravenously
In the leaky vessels, the carbon particles are trapped
between the endothelium and the basement membrane
Thus, the blood vessels showing an increase in
permeability are "labelled" with carbon.
ii. Slowing of the circulation:
This is soon followed by slowing of thecirculation. This change is essential foremigration of the leukocytes.
Retardation is achieved in four ways:
1) By increasing the capillary bed in the area
2) By swelling of the endothelial cells lining thecapillaries
3) Haemoconcentration
4) Margination of the leukocytes
iii. Stasis:
When the above factors markedly reduce the
flow, blood barely moves through the vessels,
and stasis is produced.
This situation is ideal for the escape of molecular
and cellular elements essential for the formation
of inflammatory exudate.
3. Changes in the Bloodstream
There is redistribution of the cellular elements of the
bloodstream
Normally in the bloodstream of a vessel - two distinct
zones
Axial or central stream - cellular elements are held in the
centre by the centripetal force
Plasmatic or Peripheral stream - a clear zone consisting
mainly of plasma in contact with the wall of the vessel by
centrifugal force
As the blood flow slows, the centripetal force of the
bloodstream is overcome by the centrifugal force and the
leukocytes fall out of the axial stream and marginate
towards periphery of blood vessels is called margination of
leukocytes
Cont…
After margination leukocytes tumble (roll over and over)
slowly along the endothelial surface and adhere transiently
This process of brief, loose sticking of leukocytes to the
endothelium is called rolling
Finally , leukocytes come to rest at some point where they
adhere firmly
This firm sticking of leukocytes to the endothelium is called
adhesion
In time, the endothelium is virtually lined by white cells.
This appearance is called pavementing
4. Exudation of Plasma
Following increased vascular permeability, fluid
part of the blood escapes into the inflamed area
This is known as exudation. The accumulated
plasma outside the vessel is known as an
inflammatory exudate.
5. Emigration of Leukocytes
The process of luekocytes moving outside the blood
vessels is known as emigration
After firm adhesion leukocytes insert their pseudopodes
into their endothelial junctions
Then they squeeze through this gaps & occupy a position
between the endothelial cell & basement membrane
They stay here for short a period
Finally they crawl through the basement membrane &
escape into extra vascular space. All the WBCs use the
same pathway
The force which attracts the leukocytes in to inflamed tissue
is called chemotaxis
Cont…
This is the unidirectional migration of cells towards an
attractant
Some chemotactic factors act on neutrophils , some on
monocytes
For e.g Bacterial products, C5a,LTB4 - attract neutrophils
6. Diapedesis of Erythrocytes
Red cells may also leave the intact blood vessels
They have no power of movement and are pushed out of
the vessel passively by the intravascular pressure
following emigration of leukocytes called Diapedesis
Escape of RBC through the intact blood vessels
In severe injury RBC may also enter into tissue following
breakage of vessels wall called as Rhexis