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What is happening at time of inflammation when blood vessels become "leaky"? What are the "substances" involved?
The endothelial cells contract which widens the intercellular gaps of venules. Caused by:
- 1. histamines
- 2. bradykinins
- 3. leukotrienes
- 4. Substance P
What is the effect of of exudates and presence/lack of protein inside/outside the blood vessel?
Loss of protein from the blood vessel causes:
- Decreased intravascular osmotic pressure/increased osmotic pressure of interstitial fluid
- Result in outflow of fluid to interstitial cells and edema
What is effect of cytokine mediators
TNF-Tumor Necrosis Factor
They induce endothelial cell junction retraction through cytoskeleton reorganization, 4-6 hours post injury
How might the endothelium get damaged during inflammation?
Marginating and cell-adherent leukocytes may pile-up and damage the endothelium through activation and release of toxic oxygen radicals and proteolytic enzymes making the vessels leaky
What is Vascular Endothelial Growth Factor?
A mediator that may cause increased transcytosis via intracellular vesicles which travel from the luminal to basement membrane surface of the endothelial cell
Describe steps of Leukocyte exudation
- Margination, rolling and adhesion
- Diapedesis (transmigration across the endothelium)
- Migration towards chemotactic stimulus
- Phagocytosis of pathogen
What are the selectin mediators for leukocyte's early rolling and adhesion?
How are they upregulated?
- Selectin family
- E-Selectin (Endothelium)
- P-selectin (platelets, endothelium)
- L-selectin ( bind other surface molecules)
They are upregulated on endothelium by cytokines (TNF, IL-1)
What are the mediators for cellular adhesion during margination, rolling and adhesion phase? Where are they located?
- ICAM- Inter-Cellular Adhesion Molecule 1
- VCAM-Vascular Cell Adhesion Molecule
Located on endothelial cells
Activated by histamine, a cytokine released from resdient macrophages near site of injury
What do the leukocytes do as they migrate through the endothelium?
They secrete collagenase enzymes to degreade the basal membrane
What does the term chemotaxis mean?
Locomotion, movement, oriented along a chemical gradient.
What type of leukocyte is the first to migrate and most common in acute inflammation
What is the most common leukocyte?
Neutrophils are the first to migrate and most common leukocyte in acute inflammation
Monocyte is most common after 24 hours
What are the molecules in the plasma when in high levels serve as markers for atherosclerosis and development of Chronic heart disease?
The presence of what is another hallmark of chronic inflammation?
Monocytes and macrophages
What are chemokines
They act primarily as chemoattractants for specific types of leukocytes. Stimulate leukocyte recruitment in inflammation
What are the metabolites that are involved as mediators during inflammatory process?
Arachidonic acid metabolites (eicosanoids):
Prostaglandins and Thromboxane via cyclooxygenase pathway
Leukotrienes: via lipoxygenase pathway
What do Prostaglandins and Thromboxane do during inflammation?
- Cause vasodilation
- Prolong edema
- Produce protective gastric mucosa
What do Leukotrienes do during inflammation?
- They are chemotaxins
- Increase vascular permeability