vascular changes in inflamation

it contain information regarding vascular changes happen in during process of inflamation

1. Vascular changes of inflammation

2. Introduction Julius Cohnheim (1839-1884) was the first to describe vascular changes in 1877 by spreading the mesentery of a frog and observed the flow of blood through the vessels , following the application of a drop of dilute acetic acid

3. The vascular changes are: Change in blood vessels Momentary vasoconstriction Vasodilatation Change in the rate of blood flow Increased vascular permeability Slowing of the circulation Stasis Change in the blood stream Exudation of plasma Emigration of luecocytes Diapedesis of erythrocytes

4. 1.Changes in the blood vessels 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

5. 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.

6. 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.

7. 2. Changes in the Rate of Flow The early vasodilation results in increased blood flow This is soon followed by slowing of the circulation which is brought about by increased permeability of the microvasculature ( venules , small veins, and capillaries), and leads to the outpouring of protein rich fluid into the extravascular tissues This results in concentration of red cells in small vessels and increased viscosity of the blood In tissue sections, this is seen as dilated small vessels packed with red cells - a condition termed stasis.

8. 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.

9. Mechanisms of Increased Vascular Permeability 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.

10. 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

11. 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. E ndothelial retraction takes 4-6 hours to develop and persists for 24 hours or more

12. 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

13. 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

14. 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 .

15. Increased transcytosis : Transcytosis occurs across channels formed by fusion of uncoated vesicles Certain mediators, e.g., vascular endothelial growth factor (VEGF) cause increased transcytosis

16. 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

17. Estimation of Increased Vascular Permeability Increased vascular permeability can be demonstrated or quantitated , experimentally, in several ways: Dye technique (macroscopic method) (2) Colloidal carbon technique (microscopic method)

18. 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

19. 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.

20. Slowing of the circulation: This is soon followed by slowing of the circulation. This change is essential for emigration of the leukocytes . Retardation is achieved in four ways : By increasing the capillary bed in the area By swelling of the endothelial cells lining the capillaries Haemoconcentration Margination of the leukocytes

21. 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.

22. 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

23. 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

24. 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 .

25. 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

26. 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

27. 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

28. Thank you… Dr.Ankur patel …