In acute inflammation due to the contraction of endothelial cell cytoskeleton, which of the following results -
Ans. is 'b' i.e., Early transient increase in permeability Increased vascular permeability o The hallmark of acute inflammation is increased vascular permeability The following mechanisms have ben proposed for increased permeability. i) Formation of endothelial gaps in venules (immediate transient response) This is the most common mechanism of vascular leakage and is caused due to the mediators such as histamine, bradykinin, leukotrienes, neuropeptide sustance Classically this type of leakage affects venules, leaving capillaries and aerioles unaffected. The precise reason for this restriction to venules is unceain, it may be because there is greater density of receptors for mediators in venular endothelium. Binding of mediators such as histamine to their receptors on endothelial cells activate intracellular signaling pathways that lead to phosphorylation of contractile and cytoskeletal proteins such as myosin. These proteins contract leading to contraction of endothelial cells and separation of intercellularjunction. Thus the gaps in the vascular endothelium are largely intercellular or close to the intercellular junctions. This type of leakage occurs rapidly after exposure to the mediator and is usually reversible and sho lived (15-30 minutes), it is thus known as immediate transient response. Cytokines such as interleukin-1 (IL-1), tumour necrosis factor (TNF) and interferon y also increase vascular permeability by inducing a structural reorganization of the cytoskeleton such that the endothelial cells retract from one another. In contrast to the histamine effect, the cytokine induced response is somewhat delayed (4-6 hrs) and long lived (24 hrs or more). Direct endothelial injury resulting in endothelial cell necrosis and detachment (immediate sustained response) This effect is usually encountered in necrotizing injuries and is due to direct damage to the endothelium by injurious stimulus e.g severe burns or lytic infections. The reaction is known as immediate sustained response because the leakage stas immediately after the injury and is sustained at high levels for several hours until the damaged vessels are thrombosed or repaired. o All levels of microcirculation are affected including venules, capillaries and aerioles. iii) Delayed prolonged leakage This is curious but relatively common type of increased permeability that begins after a delay of 2-12 hours, lasts for several hours or even days and involves venules as well as capillaries. This type of leakage is caused by mild to moderate thermal injury, X-ray radiation or ultraviolet radiation and ceain bacterial toxins. It is caused either by direct effect of injurious agent or by cytokine mediated endothelial retraction. iv) Leucocyte mediated endothelial injury Leucocytes adhere to endothelium relatively early in inflammation. These leucocytes may be activated releasing toxic oxygen species and proteolytic enzymes which then cause endothelial injury or detachment. This type of leakage affects venules (mostly); pulmonary & glomerular capillaries. v) Increased transcytosis across the endothelial cytoplasm Transcytosis occurs across channels consisting of clusters of interconnected uncoated vesicles and vacuoles called the vesiculovacuolar organelle, many of which are located close to intercellular junctions. It usually occurs in venules. vi) Leakage from new blood vessels During repair formation of new vessels occur (angiogenesis) New vessel sprouts, remain leaky until the endothelial cells mature.
Delayed transient increase in permeability
Early transient increase in permeability
Delayed permanent increase in permeability
Early permanent increase in permeability