Flashcards in Chapter 2. Inflammation and Repair - Acute Inflammation Deck (46)
what is the definition of acute inflammation?
transient and early response to injury; chemical, vascular, and cellular
-involves release of chemical mediators
-leads to sterotypic vessel and leukocyte responses
-NOT synonym for infection, but can be a side efffect
what are cardinal signs of inflammation? the pathology behind it?
1. rubor (readness) and calor (heat)
-histamine-mediated vasodilation of arterioles
2. tumor (swelling/edema)
-histamine-mediated increase in permeability of venules causing increased fluid in interstitial space
3. dolor (pain)
-PGE2 sensitizes specialized nerve endings to effects of bradykinin and other pain mediators
4. functio laesa (loss of function)
what are stimuli for acute inflammation?
2. immune reactions
3. tissue necrosis, trauma, radiation, burns, foreign bodies, etc.
what is the sequence of vascular events in acute inflammation?
1. vasoconstriction of arterioles (neurogenic reflex that lasts only seconds)
2. vasodilation of arterioles
-histamine and other vasodilators relax smooth muscle, causing increased blood flow, which increases hydrostatic pressure
3. increased permeability of venules
-histamine and other mediators contract endothelial cells, producing endothelial gaps
--tight junctions are simpler in venules than arterioles
-transudate )protein and cell-poor fluid) moves into interstitial tissue
4. swelling of tissue (edema) due to net outflow of fluid surpassing lymphatic ability to remove fluid
5. reduced blood flow (decrease in hydrostatic pressure caused by outflow of fluid into interstitial tissue
what is the sequence of cellular events in response to bacterial infection?
neutrophils are primary leukocytes in acute inflammation
1. marginization (RBC aggregate into rouleaux in venules, and neutrophils are pushed from central axial column to periphery)
2. rolling (due to activation of selectin adhesion molecules on surface of neutrophils and endothelial cells; bind to selectins)
3. adhesion (adhesins like integrin firmly binds neutrophils to endothelial cells' ICAM and VCAM)
4. transmigration (diapedesis); neutrophils dissolve basement membrane to enter interstitial tissue
5. chemotaxis (neutrophils follow chemical gradients that lead to infection site)
what activates adhesion molecules?
C3a and LTB4 (leukotriene)
-endotoxins enhance activation to cause neutropenia (decreased peripheral blood count)
what inhibits activation of adhesion molecules?
catecholamines, corticosteroids, and lithium
-neutrophil count increases (neutrophil leukocytosis)
what are ICAM and VCAM? what are they activated by?
endothelial cell adhesion molecules (intracellular and vascular cell adhesion molecules)
-activated by IL-1 and TNF
what is leukocyte adhesion deficiency (LAD)?
autosomal recessive disorders
-LAD1 is deficiency of CD11a:CD18
-LAD2 is deficiency of selectin that binds neutrophils
-have delayed separation of umbilical cord (neutrophil enzymes important in separation) and severe gingivitis, poor wound healing, neutrophilic leukocytosis (loss of marginating pool)
what is exudate?
fluid rich in proteins and cells that accumulates in interstitial tissue during diapedesis
-dilutes bacterial toxins and provides opsonins to assist in phagocytosis
what are chemotactic mediators?
C5a, LTB4, bacterial products, and IL-8
-these bind to neutrophil receptors, which releases Ca to increase neutrophil motility
what are the 3 steps of phagocytosis?
what are important opsonins?
IgG and C3b, along with other proteins like C-reactive protein
-but neutrophils only have receptors for IgG and C3b
what is Bruton's agammaglobulinemia?
what is Chediak-Higashi syndrome?
defect in microtuble function that prevents phagolysosomes formation
what is the O2-dependent myeloperoxidase (MPO) system? what are
most potent microbicidal system only present in neutrophils and monocytes
-production of superoxide free radicals (NADPH oxidase converts O2 to -O2., which releases energy as respiratory/oxidative burst
-production of peroxide (superoxide dismutase converts -O2. to H2O2, which is neutralized by glutathione peroxidase
--some peroxide is converted to hydroxyl FR by Fe
-production of bleach (MPO combines H2O2 with Cl- to form HOCl. FR to kill bacteria)
what is chronic granulomatous disease? what are some signs?
XLR or AR disease
-absent NADPH oxidase and reduced -O2. production causes absent respiratory burst
-macrophages fuse together to form multinucleated giant cells to take over neutrophil function
-severe infections involving lungs, skin, visceral organs, bones
-classic screening test is colorless NBT dye, which becomes blue if respiratory burst intact (negative CGD)
what is MPO deficiency?
AR that has normal respiratory burst (both .O2- and H2O2 are made), but HOCl. is not
what is the O2-independent system? two examples?
bacterial killing from substances in leukocyte granules
-ex: lactoferrin (binds Fe necessary for bacterial reproduction) and major basic protein (eosinophil product cytotoxic to helminths)
what are chemical mediators?
derive from plasma, leukocytes, local tissue, and bacterial products
-have short lives (seconds to minutes)
-have local and systemic effects, with many diverse functions
what is the most important chemical mediator of acute inflammation?
what are types of acute inflammation?
1. purulent (suppurative) inflammation
2. fibrinous inflammation
3. serous inflammation
4. pseudomembranous inflammation
what is purulent inflammation and an example?
suppurative; localized proliferation of pus-forming organisms (like S. aureus, that has coagulase that cleaves fibrinogen into fibrin and traps bacteria and neutrophils)
what is fibrinous inflammation
due to increased vessel permeability, with deposition of fibrin-rich exudate
-often on serosal lining of pericardium, peritoneum, or pleura (danger of adhesions)
what is the most common cause of a skin abscess?
what are the three arachidonic acid metabolites that act as chemical mediators?
prostaglandins, thromboxane A2, and leukotrienes
what is the source and function of prostaglandins?
source: macrophages, endothelial cells, and platelets
-PGH2 is the major precursor of PGs and thromboxanes
PGE2: vasodilation, pain, and fever
PGI2: vasodilation, and inhibition of platelet aggregation
what is the source and function of thromboxane A2?
from platelets, and converted from GH2 by thromboxane synthase
for vasoconstriction and platelet aggregation
what is the source and function of leukotrienes (LTs)
leukocytes, and lipoxygenase-mediated hydroxylation
LTB4: chemotaxis and activation of neutrophil adhesion molecules
LTC4, LTD4, LTE4: casoconstriction, increased venular permeability, bronchoconstriction