10. physiological response to inflammation Flashcards
five cardinal symptoms associated with acute inflammation and tissue damage
pain
redness
heat
loss of function
swelling
role of microcirculation
- acute and intermediate inflammation
- oedema formation
- long term inflammatory conditions
in a normal state, what do blood flow through tissue depend on?
a) Systemic arterial pressure (function of CO and total peripheral resistance)
b) Local vascular resistance (arteriolar tone)
i) Neuronal constrictor and dilator influences
(eg. noradrenaline and sensory nerves)
ii) Endocrine and paracrine hormones
(angiotensin II & PGs)
iii) pO2 and pCO2
vasodilators in the acute inflammatory state
what effects does this have
prevailing physiological influences on arterial tone are overriden by vasodilators from: Tissue fluids and cells, nerve endings, leukocytes
Histamine - Skin mast cells - vasodilatation LOCAL REDNESS
Bradykinin (Bk) - direct vasodilatation and release of endothelial prostoglandins (PGs) relaxes smooth muscle
Bk also stimulates nociceptors (sensitized by PGs) PAIN
Vasodilator peptides in sensory nerves (dilator effect on smooth muscle)
+ *Substance P .
*Vasoactive Intestinal polypeptide (VIP)
+ Calcitonin Gene-related peptide (CGRP)
increase in bloodflow- redness
increase in local temp
Microcirculation in acute (1h) extravasion
what does the monolayer of capillaries act as
permeability barrier
plasma proteins and water stay within lumen of blood vessel
difference between arteriolar and venular endothelium in acute extravasian
arteriolar: proteins are distributed evenly
venular: selective distribution around gaps/ pores between cells (if they contract, junction opens- proteins can move into extra vascular space- water follows- swelling)
why is the venular site ideal for modification of microvascular permeability
- low hydrostatic pressure
- large SA
why does oedema occur during extravasian
leakage of plasma proteins and fluids into extracellular space from:
endothelial damage and post capillary venule modulation
agents that increase venular permeability
contract pore proteins by elevating Ca2+
Histamine - H1 receptors
Bradykinin
Leukotriene C4 and D4 and platelet activating factor (PAF)
agents that decrease venular permeability
relax pore proteins by cyclic AMP
ß2-adrenoceptor agonists - Terbutaline, Salbutamol relaxation of contractile proteins (anti-inflammatory like effect)
PGI2
what is the ‘TRIPLE RESPONSE’ in the SKIN- Chemical irritant/bee sting
- initial flush in the area of damage- release of histamine from mast cells and vasodilation
- flare - extensive vasodilation in undamaged area surrounding flush (redness), Orthodromic activation of sensory nerves (sensation of pain and itching) and antidromic activation of branches causes release of substance P, CGRP and VIP
- wheal- oedema (swelling) in damaged area
Later event associated with the ‘flush’ - direct damage to the endothelium, activation of complement and/or mediator modification of vascular permeability
leads to protein extravasation.
what do oral anti-histamines do
reduce magnititude of histamine-induced temp change but does NOT abolish the response.
what happens to microcirculation in intermediate (>2 hour) extravasion?
release of TNFa and activation of complement
- attracts neutrophils to area
Activation of vascular endothelium by cytokines and release of the interleukin-8
cell adhesion molecules
neutrophil dependent extravasion
Release of IL-8 from activated endothelium
Stimulate neutrophil G protein coupled chemokine receptor
Permits interaction between integrin and endothelial Ig CAM
Promotes adhesion of neutrophil to endothelium (2 hours after injury)
Neutrophils cross endothelium (diapedasis) and migrate towards chemoattractant at site of injury.
