Acute inflammation 2 By Dr. S. Homathy

Mechanism of formation of transudate

Starling’s law 'relating to fluid flux between vessels and interstitium

‘Starlg’s law’ relating to fluid flux between vessels and interstitium

Mechanism of increased permeability Endothelial “gaps”- due to endothelial cell contraction Direct endothelial Injury Leukocyte mediated Injury Increased transocytosis (endo/exo) Leakage from new vessels Endothelial retraction

Endothelial cell contraction leads to intercellular gaps in venules Reversible process elicited by Histamines, bradykinins, leukotrienes cause an early, brief (15 – 30 min.) immediate transient response in the form of endothelial cell contraction that widens intercellular gaps of venules (not arterioles, capillaries)

Endothelial cell retraction Cytokine mediators (TNF, IL-1) induce endothelial cell junction retraction through cytoskeleton reorganization 4 – 6 hrs post injury, lasting 24 hrs or more

Direct endothelial cell injury causing endothelial cell necrosis and detachment Severe injuries(burns, infection) may cause immediate direct endothelial cell damage (necrosis, detachment) making them leaky until they are repaired immediate sustained response (immediately after injury and to persist for hours / days until the damaged vessel is repaired)

may cause delayed damage as in thermal or UV injury or some bacterial toxins delayed prolonged leakage Start 2-12 hours after injury and persist several hours or even days

Leukocyte mediated endothelial injury Marginating and endothelial cell-adherent leukocytes may pile-up damage the endothelium through activation and release of toxic oxygen radicals proteolytic enzymes (leukocyte-dependent endothelial cell injury) making the vessel leaky Mosly in venules and pulmonary capilaries Late response Long – lived (hour)

Increased transcytosis Certain mediators (VEGF) may cause increased transcytosis via intracellular vesicles which travel from the luminal to basement membrane surface of the endothelial cell Usually in venules

Leakage from regenerating capillaries New vessels remain leaky until endothelial cells differentiate sufficiently to form intercellular junction New endothelial cells also have increased expression of receptors for vasoactive mediators Directly induce increased vascular permeability via transcytosis.

All or any combination of these events may occur in response to a given stimulus

Exudate Tissue oedema Neutrophil margination …. And emigration

This example of edema with inflammation is not trivial at all: there is marked laryngeal edema such that the airway is narrowed. This is life-threatening. fluid collections can be serious depending upon their location.

Here is an example of fluid collection into a body cavity, or an effusion. This is a right pleural effusion (in a baby). Note the clear, pale yellow appearance of the fluid. This is a serous effusion.

Effusions into body cavities can be further described as follows: Serous: a transudate with mainly edema fluid and few cells. Serosanguinous: an effusion with red blood cells. Fibrinous (serofibrinous): fibrin strands are derived from a protein-rich exudate. Purulent: numerous PMN's are present. Also called "empyema" in the pleural space.

Pus: A purulent exudate an inflammatory exudate rich in leukocytes (mostly neutrophils) and parenchymal cell debris.

Fibrinous pericarditis strands of stringy pale fibrin between visceral and parietal pericardium.

Leukocyte exudation / Leukocyte cellular events Leukocytes leave the vasculature routinely through the following sequence of events: Margination and rolling Adhesion and transmigration/ Diapedesis (trans-migration across the endothelium)

Chemotaxis and activation(Migration toward a chemotactic stimuli from the source of tissue injury and become active) They are then free to participate in: Phagocytosis and degranulation Leukocyte-induced tissue injury

Leukocyte extravasation and phagocytosis

Rolling, adhesion, and transmigration are mediated by the binding of complementary adhesion molecule on leukocytes and endothelial surfaces

Margination (pavementaion) of WBC Usually circulating cells are swept by laminar flow against the vessels. In which the red cells are in the center and the WBC are in the periphery Can interact with the lining endothelial cells