Acute Inflammation Flashcards
Acute Inflammation
-edema and neutrophils
Coordinated, multistep, rapid (hours to days) response to injury or infection
goal: to deliver immune cells, plasma proteins (Ab’s, immunomodulators), chemical mediators to site
What are the cardinal features of inflammation
heat (calor)- vasodilation
redness (rubor)- vasodilation
pain (dolor)- compression on nerve ending from edema
swelling (tumor)
What are the stumuli for acute inflammation?
- infections (baterial/viral/fungal/parasitic)
- tissue necrosis (ischemia/trauma/physical or chemical injury)
- foreign bodies (dirt/sutures/medical devices)
- immune/autoimmune reactions (‘bystandard’ damage to self)
What are the alteration in acute inflammation?
- Increased blood flow–>vasodilation–>calor, rubor (erythemia)
- slowing of circulation (congestion and increased permeability of microvaculature; causing extravasation of fluid (tumor), hemoconcentration, statis, margination of leukocytes)
- mechanisms of increased vascular permeability
a. endothelial contraction (histamine, and other inflam mediators)
b. endothelia injury (eg. burns)
c. neutrophil-mediated injury
What does the slides represent?
Normal lung–>vascular congestion and stasis–>leukocyte infiltrate.
How do lymphatic vessels respond to inflammation?
Increased lymphatic drainage of edema fluid
Lymphangitis
inflammation of lymphatic-red streaks below the skin
lymphadenitis
inflammation in draining LN
what does lymphagitis physical finding indicate?
finding that indicates local wound infection
What are the mediators for vasodilation?
prostaglandins
NO
histamine
what are the mediators for increased vascular permeability?
histamine, bradykinin, C3a, C5a
what are the mediators in fever?
TNF, prostaglandins
What are the mediators in pain?
prostaglandins, bradykinin
Mediators of the cardinal signs
rubor: histamine
calor: histamine
tumor: histamine
Dolor: PGE2, bradykinin
What are the mediator involved in vasocontriction?
TXA2
What are the mediators involved in chemotaxis?
C5a, LTB4, IL8
Neutrophils play a huge role in what type of immunity?
- major actor in innate immunity
- normal adult ANC~1500-2000ul
1X 1011produced daily
90+% sitting in bone marrow, circulating amt increase 10fold in setting of infection
circulating half-life of 6-10hrs
Neutrophil granules
- specific granules (lactoferrin, lysozyme, alkaline phosphate, type IV collagenase, Leukocyte adhesion molecules, plasminogen activation, phopholipase A2)
- azurophil granules (*myloperoxisase, etc)
What are the steps in leukocyte recruitment to sites of infection and injury?
- normal: tumbling along in bloodstream
- slowed flow (stasis)–> migration, rolling, and adhesion to an **activated **endothelium
- migration across the vessel wall (diapedesis)
- migration down chemotactic gradiets
Endothelial activation
(secondary to tissue damage or infection)
- cytokines secreted from MO attrack leukocytes/neutrophils to endothelial wall.
Migration
vasodilation slow blood flow in post cap venules. white blood cells get pushed against the wall so opportunity to interact with endothelium, red cels flow in center bc they are smaller.
Rolling
leuko attach to adhesion molecules and detach to tumble on surface. cytokines, etc stimulate expression of selection on leuko and endo.
- p-selectins released form wiebel palade (wilkerbran/pselectin proteins) bodies; mediated by histamine
- e-selectin is induced by TNF and IL-1
- selectins bind to sialyl lewis X on leukocytes, which results in rolling.
Adhesion
- adhesion molecules (ICAM and VCAM) are upregulated on endothelium by TNF and IL-1
- Integrins are upregulated on leukocytes by C5a and LTB4.
- interaction btw CAMS and integrins results in firm adhesion of leukocytes to vessel wall
Transmigration/Diapedesis
- leukocytes transmigrate across endothelium of postcap venules move towards chemical attractants (chemotaxis)
- attracted by bacterial products IL-8, C5a, LTB4
