Inflammation Flashcards
An inflammatory reaction is
A pathophysiological process which i) destroys ii) dilutes iii) walls off an inflammatory initiating agent: -> microbrial infection, noxious stimuli, neoplasm trauma
Basic physiological events:
- Vascular- dilation
- Cellular- anti-microbial
- Induction - antigen presents
- Effect - lymphocyte recruitment
Outline vascular - dilation phase
- Increased vasodilation increases vascular permeability
- Fluid extravasation
- Endothelial cell activation -> express CAMS
- Leukocytes in blood vessel adhere to endhothelium
- Transmigrate to site inflammation
Cellular response involves which 2 types of cells :
- Polymorph nuclear cells (PMN’s) e.g. neutropil
- > phagocytosis microbial nature -> respiratory burst
- > proteases/ recruit more leukocytes - Monocytes -> differentiate into macrophages which
i) phagocytose
ii) release host inflammation mediators
- > reactive o2 species
- lipid mediators
- cytokines/ chemokines - Present antigen to lymphocytes
Henry Dale’s criteria for chemical mediator:
Be present, cause inflammation, releived if synthesis. release manipulated
Histamine is released from _____ or ____ by a variety of stimuli including XYZ
Mast cells/ basophilis by
X: IGE cross linking
Y: Amphylation C5a and C3a
Z: Morphine
H1 mediates
endo cell activation by rounding up -> I.C. spaces form, arteriolar and arterial relaxation
Histamine is formed by
Histidine by histidine decarboxylase
H1 antagonists that cross BBB and what they’re used for:
Gaq - diphenhydramine, chlopheniramine
-> sedation, motionsickness, allergies (but drowsy)
H1 antagonists that don’t cross BBB
Cetirizine, terfenadrine
-> allergies (partially effective)
H2 antagonists
Gas
e.g. rantidine
suppression gastrin secretion
-> heals duodenal ulcers
Types of kinins and origins
Bradykinins + kallidin (lys-bradykinin)
-> formed from plasma protein precursors (kinninogens)
Kallikans
Enzymes that produce kinin from kinnogens
Kinin is destroyed by X and Y with a plasma half life of
X- Carboxypeptidase N
Y- Angiotensin coverting enzyme
20 minutes
Kinin functions and mediators
- Vasodilators, increase venular permeability, cause pain + contract smooth muscle
- Actions mediated by B2 receptors but B1 also exist/ histamine. prostaglindin release
How does beta 2 mediate kinin function?
- constitutive
- acts through other mediators
- NO + prostaglandins
- agonist: bradykinin, kalidin
- antagonist : icibant HOE140
How does beta 1 mediate kinin function?
- induced via cytokines
- not internalised
- agonist: des-arg kalidin DABK (des-arg bradykinin)
- antagonist: des-arg icibant
Prostaglandin characteristics
20 carbon with HO group at C15
Prostaglandin E.synthase:
1) cytosolic: constituitive production
2) membrane: inflammatory mediators e.g. arachindonic acid -> prostenoid + relevant synthase (COX)
How do the EP receptors differ?
- Bronchial G.I, sm mu contraction, pain
- Bronchodilation, vasodilation, stimulation of intestinal fluid secretion + G.I. sm. muscle relaxation
- Intestinal Sm. mu. contraction gastric acid secretion inhibition, increase gastrine mucus secretion
- Bronchial constriction + vaso D, leukocyte suppression
How does PGE2 cause fever?
Hypothalamus
How does PGE2 cause pain?
Induces hyperalgesia at peripheral terminals of primary afferent nociceptors and spine
How does PGE2 cause oedema?
Synergy with other mediators
PGE2 and leukocytes
Inhibits leukocytes
PGD2
Synthase found predominantly in mast cells and brain
DP- receptors: Vasodilatation, inhibit platelet aggregation, Relaxation GI muscle & uterine
TP-receptors:- Bronchoconstrictor
CRTH 2:- Chemoattractant for Th2 cells
PGF2
FP-receptors:- Smooth muscle contraction, Bronchoconstriction, Reproductive physiology
PGI2
prostacyclin
- > synthase found in vascular endothelium
- IP- receptors: Vasodilatation, Inhibit platelet aggregation, renin release
Thromboxane A2
Synthase found in platelets
TP receptors: Vasoconstriction, platelet aggregation
Cytokine + Chemokine characteristics
Simple polypeptides/ glycoprotein with molecular weight <30KD -> production transient
- bind to high affinity CS receptors
- > alter gene expression in target cells
Binding affinity of cytokine + chemokines
10-9 - 10-12 M