8/27/13 Flashcards
3 of the 5 cardinal signs of inflammation that have to do with vascular changes
Redness, swelling, heat
What happens immediately following an injury?
transient vasoconstriction
Describe the two processes that occur after the transient vasoconstriction after an injury
vasodilation of the arteriolar side of the capillary bed, and as fluid moves into the interstitium stasis occurs in the blood flow
What is the threshold of the rate of amount of fluid into the interstitium above which edema occurs?
2ml/min
Describe the role of hydrostatic and oncotic pressure in acute inflammation?
The arteriolar dilates leading to increased blood flow and hydrostatic pressure. There is more fluid in the interstitium. As proteins start to enter the interstitium, the oncotic pressure on the venule side decreases leading to less fluid being taken up in the blood vessel
Watery ultrafiltrate of the plasma which is very low in protein content
transudate
Ultrafiltrate that contains protein
exudate
Where does most endothelial leakage occur (arterioles/capillary bed/venules)?
Venules
Stimulated by histamine, happens in the venule only immediately and is transient, and is a type of endothelial gap
endothelial contraction
Happens after hours but is long lasting, stimulated by TNF and IL-1, type of endothelial gap that happens in venules
endothelial retraction
Direct injury to endothelial by way of UV radiation, thermal injury, bacterial toxins leads to cell death by this process
Apoptosis
Direct injury by severe burns and infection in endothelial cells lead to cell death by this process
Necrosis
How do leukocytes contribute to endothelial injury?
They secrete reactive oxygen species and proteolytic enzymes
Name all 6 types of endothelial occurences that weaken the endothelial lining
endothelial contraction, endothelial retraction,direct endothelial injury, leukocyte-dependent endothelial injury, increased endothelial trancytosis, leakage due to angiogensis
migration of leukocytes from the blood into the tissue is called
extravastion
Leaukocytes are in the periphery/middle in normal blood flow
periphery
Selectins bind to what type of molecule?
Sugars on the glycoproteins
Name the three groups of interactions via selectins between leukocytes and endothelial cells
L-selectin–CD34
Sialyl-Lewis X GP– E selectin
Sialyl-Lewis X GP– P selectin
Histamine and thrombin stimulates this selectin to translocate to the surface
Selectin P from the Weibel-Palade body
TNF and IL-1 stimulate the translocation of this selectin to the surface
Selectin E
What increases integrin’s affinity to ICAM and VCAM
due to chemokines
TNF and IL-1 increase the expression of these endothelial adhesion molecules
ICAM and VCAM
Diapedesis of leukocytes is mediated by what?
PECAM 1
4 chemotatic agents for leukocytes and which type of receptor they bind too
soluble bacterial prodcuts, C5a, IL-8, arachidonic acid from membrane/ G-receptor
Describe the G-protein receptor mechanism in leukocytes
Phospholipase cleaves PIP2–> IP3 and DAG–> IP3 signals the release of calcium which leads to the creation of pseudopods and modulates leukocyte adhesion factors–> DAG leads to the activation of PKC which leads to the degrnulation/secretion of lysosomal enzymes and oxidative burst–> DAG and high intracellular Ca2+ also leads to the activation of phospholipase A2 which metabolizes the membrane phospholipids into arachidonic acid
What are the three molecules that are bound to the microbe that signal the leukocyte to engulf it
C3, collectin, IgG
The lysosomes of neutrophils contribute what to the killing and degradation of microbes
MPO
Describe the oxidative steps that lead to the destruction of the microbe
Cytoplasm and NADPH oxidases convert oxygen into superoxide anion–> superoxide anion is converted to hydrogen peroxide by dismutase–> MPO with Cl- converted hydrogen peroxide to hypochlorous radical
Defects in leukocyte adhesion
LAD-1–> defect in the beta chain of integrin
LAD-2–> defect in the Sialyl-Lewis X GP (selectin problems)
Defects in the microbicidial activity
CGD–> NADPH oxidase mutation, superoxide is not formed and granuloma formed
Che’diak-Higashi syndrome–> lysosomes do not meet with phagosome
For the three systemic mediators, which include_____, this blood factor helps activate them
Complement, kinins, coagulation factors/Hageman factor (factor XII)
What types of organelles activate factor XII in the presence of a cofactor
basement membrane, collagen, platelets
Describe the kinin cascade
Activated factor XII converts prekallikrein to kallikrein–>Kallikrein converts HMWK to bradykinin–> Kallikrein also stimulates the increase of more active factor XII–> bradykinin increase vascular permeability, vasodilation, pain, and contract bronchial smooth muscle
Describe the coagulation cascade
Factor XIIa activates factor XI–> factor XIa activates factor X–> factor Xa converts prothrombin to thrombin–> thrombin converts fibrinogen to fibrin the clotter
Describe the effects of factor Xa
Increases vascular permeability and leukocyte emigration
Describe the effects of thrombin
Increases the adhesion of leukocytes and cleaves Complement 5
Describe the effects of fibrinopeptides
Increase vascular permeability and serve as chemotaxins for leukocytes
Describe the fibrinolytic cascade
Kallikrein converts plasminogen to plasmin–> plasmin cleaves the fibrin clot–> plasmin also increases the factor XII activation–> fibrin degradation products increase vascular permeability and vasodilation–> plasmin also cleaves C3 to C3a
Which complement proteins act as anaphylatoxins and what do they do?
C3a and C5a/ they signal mast cells to degranulate
C5a proteins increase
Arachidonic acid metabolism, leukocyte integrin affinty, and chemotaxis
How do C3b proteins function as inflammatory mediators?
They act as opsonin
What results after histamine release?
Arteriolar dilation, vascular endothelial contraction, constricts large arteries, immediate permeability, quickly degraded by histaminase
What stimulates serotonin release?
Platelet aggregation
Where is substance P release?
By nerves in the lung and gut
Describe the cyclooxygenase pathway
Phospolipase converts membrane into Arachidonic acid–> cycloxgenase converts AA to prostaglandins–> in endothelium prostacyclins are released which inhibit platelet aggregation and promotes vasodilation–> in platelets thromboxane are released which promote platelet aggregation and vasoconstriction
What do leukotrienes from the lipoxygenase pathway promote?
Promote chemotaxis of neutrophils and vasocontriction
What do lipoxins fromthe lipoxygenase pathway promote?
inhibit neutrophil chemotaxis and vasoduialtion, resolution of inflammation
what part of arachidonic acid metabolism does steroids inhibit?
Inhibits phospholipase action, so AA formation prevents
what part of arachidonic acid metabolism does aspirin and NSAIDS block?
They block COX-1 and COX-2 which are essential for prostaglandins and prostacyclins (COX-1 provides protection for gastric mucosa from acid)
The problem with COX-2 inhibitors is that____
They block prostacyclins preferentially, so prostaglandins (thromboxane) promotes platelet aggregation leading to clots
Besides making AA, phospholipase A2 also releases___
Platelet activating factor
Which molecule stimulates hepatic synthesis of coagulation proteins, complement, and fibronogen in the acute phase reaction?
IL-6
What are the two types of chemokines
CXC, CC (C represents cysteine)
