Inflammation Flashcards
leukocytes
white blood cells: neutrophils lymphocytes monocytes eosinophils
4 cardinal signs of acute inflammation
- redness/rubor
- swelling/ tumor
- calor/ heat
- dolor/ pain
distinct patterns that trigger acute inflammation
pathogen associated molecular patterns - PAMPs - like bacterial cell wall
Damage Associated molecular patterns - DAMPs- like fragments of necrotic cells
step one in acute inflammation
hyperemia - dilation of blood vessels - increases blood flow to the area. accounts for the rubor/redness and calor/heat at site of inflammation
histamine and serotonin
VASOACTIVE AMINES -mediators of increased blood flow
FIRST MEDIATORS released
Stored in mast cells, basophils, and platalets and is released in response to trauma, heat, or immune reactions
Serotonin - similar effects of histamine - pre-formed in platalets
Cyclooxygenase
produces AA metabolites
Arachidonic acid (AA) metabolites
include prostaglandins, leokotrienes, lipoxins - VASODILATION
arachidonic acid metabolites
prostaglandins - involved in vasodilation
example is prostaglandins
enzyme cyclooxygenase produces the AA metabolites
inhubited by aspirin and NSAIDs
nitric oxide
NO acts on smooth muscle relaxant causing vasodilation - by endothelial cells
platalet activating factor
from cell membranes- causes platalet aggregation, in addition to vascoconstriction, bronchoconstriction, and leokocyte activation
bradykinin
kinina are vasoactive peptides from plasma proteins called kininogens
increased vascular permeability and contraction of smooth muscle, dilation of blood vessles and pain when injected into the skin
step 2 in acute inflammation
increase in vascular permeability
where does the increased vascular permeability occur?
post capillary venules - NOT LARGE ARTERIES OR VEINS - venules between endothelial cells
many factors that increase hyperemia- increased blood flow/dilation of blood vessels also increase the vascular permeability
transudate
fluids low in protein concentration and cell numbers - released across capillary beds and usually reabsorbed on the venous side or by lymphatics
exudate
fluid higher concentration of proteins and inflammatory response
edema
interstitial fluid accumulation - can be either of transudate or exudate
effusion
accumulation of fluid in A SEALED BODY CAVITY (can be removed/ directly aspirated with needle or catheter where edema cannot)
example- between the lung and chest wall is a pleural effusion
purulent exudate
large concentration of neutrophils usually due to bacteria that attracts the neutrophils - results in a cloudy appearance
example - pus
hemmorrhagic exudate
contains red blood cells due to capillary damage
third step in acute inflammation
emigration, accumulation, and activation of leukocytes
sequence of leukocyte recruitment
margination
rolling
tight adhesion
migration across vessel wall
margination
in order for leukocytes to exit the blood stream - they must accumulate to the margin of the bloodstream and come INTO CONTACT WITH VASCULAR WALL
rolling
after they have marginated - may physically contact the endothelial cells. at first it is a lose connection and interaction with adherence molecules occurs - then when appropriate adherence occurs with the endothelial cell - the leuokocyte can migrate out of the blood stream
tight adhesion
part of step 3 - integrin molecules to increase their affanity for integrin ligands on the endothelial cell surface
when tightly adhered - no more rolling
migration across the vessel wall
leuokocyte will migrate between two endothelial cell - briefly breaking the junction between the two
migration into the tissue
neutrophils will move towards specific molecules called CHEMOTACTIC FACTORS
chemotactic factors
molecules that neutrophils are attracted to when migrating into the tissue - can be proteins and lipids
pyrogens
collection of these causes fever
bacteria not directly causing the fever
stimulate the production of prostaglandins synthesis in the hypothalamic regulatory centers thus altering the thermostat controlling body temperature
tachychardia
increased heart rate
tachypnea
increase in respiratory rate
acute phase reactants
chronic inflammation
benefits of acute inflammation
remove invading pathogens or clear necrotic tissue
C3a and C5a
involved in the complement cascade system
skin blister is an example of
a serous exudate
fluid and a few cells underneath the skin
integrin activation by?
chemokines
microbe binding to CD14?
microbe direct binding to CD14 causes increase in the inflammatory pathway
superoxide (o2), hydrogen peroxide (h202), hydrogen radical (OH), peroxinitrite (OONO-)
oxygen derivatives - reactive oxygen and nitrogen metabolites
main source is from leukocytes
generation of reactive oxygen and nitrogen species
mitochondria + phagosome
NETs - neutrophil extracellular trap
extruded DNA from neutrophils that trap bacteria
histones on DNA are toxic to the bacteria
three outcomes of acute inflammation
- complete resolution
- fibrosis
- chronic inflammation
chronic inflammation
persists for more than a few days
causes of chronic inflammation
prolonged exposure to the injury/irritation
immune mediated disease (autoimmune, allergies)
persistent infections - granulomatous inflammation
cells with chronic inflammation
monocyte - macrophage when in the tissue
lymphocytes - T,B, natural killer
Eosinophils
acute phase proteins
increase in acute inflammation but stay chronically elevated unless the inflammation subsidies
examples of acute phase proteins
Interleukins 1 and 6
Tumor necrosis Factor
molecules/proteins promote the synthesis of these proteins in the liver
type 1 hypersensitivity
immediate hypersensativity
type II hypersensitivity
antibody-mediated hypersensitivity
type III hypersensitivity
immune complex hypersensitivity
type IV hypersensitivity
T-cell mediated hypersensitivity
stimuli for histamine release
Physical injury: trauma, cold, heat
Binding antibodies to mast cells
Fragments of complement C3a, C5a
therapy for acute inflammation
block histamine receptors
neutrophil chemotactic factors
CXC chemokines - IL8
C5a
Bacterial products
Platalet activating facor (PAF)
