Mediators Of Acute Inflammation Flashcards
What are the mediators of acute inflammation
1) complement derived peptides( c3a,c3b,c5a)
2) kinins
3) vasoactive amines
4) eicosanoids
5) platelet activating factor
6) cytokines
Define what is meant by mediators
And what are their properties
Biochemical mediators that are released during inflammation,intensify and propagate the inflammatory response
Soluble,diffusible molecules that can act locally and systematically
What are the complement derived peptides And what do they do
C3a,c5a,c3b Increase vascular permeability Cause smooth muscle contraction Activate leukocytes Induce mast cell degranulation C5a is a potent chemotactic factor for neutrophils and mononuclear phagocytes
What do kinins do
Contribute to both inflammation and clotting cascade
What does bradykinin do
Increases vascular permeability causing vasodilation
activates phospholipase a2 to liberate arachidonic acid
mediates the accompanying pain response
What produces vasoactive amines(seratonin and histamine)
Mast cells
Platelets
Basophils
Describe histamine (Where its stored, what does it do, factors responsible for its release)
Stored and released mainly by tissue mast cells especially of skin,GIT, respiratory tracts (also hitaminergic neurons and enterochromaffin like cells participate in its release)
Factors responsible for its release: immunological c3a and c5a mainly
Neutrophil lysosomal proteins
Directly released from some drugs eg: vancomycin, morphine, radio contract media
Action stimulated by histamine receptors H1,h2,h3 Induces vascular arteriolar dilation and capillary permeability non vascular smooth muscle contraction Eosinophil chemotaxis Nociceptors stimulation
What does h1 mediate
Allergy and inflammation by inducing vasodilation
Inc permeability of capillaries
Eosinophil chemotaxis
Sensory nerve endings’ stimulation
Contraction of non vascular smooth muscles
Activation of arousal and stimulation of vomiting center
What do H2 receptors mediate
Mainly gastric acid secretion mainly
What do h3 receptors stimulate
Pre synaptic
Mediate feedback inhibition of histamine neurotransmission release from nerve endings
Describe serotonin
Where it is, how is terminated as a neurotransmitter
5-hydroxytryptamine
Most abundant in enterochromaffin like cells in GIT and rest are in platelets, blood vessels and in brain as neurotransmitter
Action is terminated by neuronal re uptake in a process known as selective serotonin re uptake or metabolic oxidation especially catalyzed by MAO enzyme in nerve endings
What does serotonin do in Platelets Blood vessels Brain GIT
Platelets=aggregation
Blood vessels=vascular sm mainly vasocontraction and less vasodilation to some cranial vessels
Non vascular sm contraction in GIT inc propulsive activity
Brain neurotransmitter
What are the eicosanoids and describe them
Prostaglandins
Leukotrienes
Lipid derived mediators from
The phospholipid of cell membranes especially of activated leukocytes,mast cells and platelets
Play major role in inflammation,allergy and thrombosis
How are pjs and LTs produced and what are the triggers
Respective action of cylooxygenase and lipoxygenase on arachidonic acid released by action of phospholipase a2
Tissue injury
Infection
Allergens
Some chemical and toxins or inflammatory mediators(tnf-a,bradykinin)
Activate directly or indirectly PLA2 bu inc intracellular Ca2+ conc
Describe the cox pathway
Two enzymes
Cox1:found in many tissues and the pgs produced by it mainly share in normal physiological regulations
Cox2:found mainly in inflammatory cells and the pgs produced by it mainly share in pathological disorders inducing pain,fever,and inflammation
Can also help such as controlling renal flow
Potent arteriolar dilators and enhance effects of other mediators by inc small vein permeability
PGE-1
PGE-2
PGI-1
Cause sm contraction and vasoconstriction
PGF2a
Thromboxane
Induce platelet aggregation
TXA2 produced by action of COX-1
Produced by cox2 in endothelium and possess anti aggregatory aside its vasodilatory action
PGI-1
Describe the lox pathway
LTB4,LTC4,LTD4,LT2
Produced in inflammatory and allergic reactions
Strong chemoattractant and stimulates production of cytokines in neutrophils,monocytes and eosinophils and enhances expression of C3b receptors
LTB-4
Facilitate release of histamine from mast cells to induce bronchoconstriction and mucous secretion
LTC4
LTD4
LT2
Describe the platelet activating factor
What does it do
Lysophospholipid derived from phophatidlycholine of cell membrane by action of PLA2
Synthesized by mast cells,platelets, neutrophils,eosinophils
induces platelet aggregation
stimulates platelets to release vasocative amines and synthesize thromboxanes
Inc vascular permeability
Causes neutrophils to aggregate and degranulate
Describe cytokines
Produced by macrophages and lymphocytes
Major players in coordinating and controlling inflammatory response
Stimulate liver to synthesize acute phase proteins inducing complement components,coagulation factors,protease inhibitors and metal binding proteins during acute phase response
IL-1
IL-6
TNF-a
What are colony stimulating factors
GM-CSF
G-CSF
M-CSF
Cytokines that promote expansion of neutrophil,eosinophil and macrophage colonies in bone marrow whenever demanded
How drugs relieve acute inflammation
By targeting biochemical mediators
Mediators of vasodilation
Histamine,bradykinin,C3a and C5a, leukotrienes(LTC4 and LTD4)
Prostaglandins(PGI2,PGE2 and PGD2)
Mediators of mast cell degranulation
C3a,c5a
Mediators of chemotaxis
IL8
PAF
C5a
Histamine
Mediators of lysosomal granule release
C5a
IL8
PAF
Mediators of phagocytosis
C3b
Mediators of pain
PGE2
Bradykinin
Histamine
Mediators of fever
IL-1
IL-6
Tnf-a
PGE2
