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