10. physiological response to inflammation Flashcards

1
Q

five cardinal symptoms associated with acute inflammation and tissue damage

A

pain

redness

heat

loss of function

swelling

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2
Q
A
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3
Q

role of microcirculation

A
  1. acute and intermediate inflammation
  2. oedema formation
  3. long term inflammatory conditions
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4
Q
A
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5
Q

in a normal state, what do blood flow through tissue depend on?

A

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

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6
Q

vasodilators in the acute inflammatory state

what effects does this have

A

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

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7
Q

Microcirculation in acute (1h) extravasion

what does the monolayer of capillaries act as

A

permeability barrier

plasma proteins and water stay within lumen of blood vessel

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8
Q

difference between arteriolar and venular endothelium in acute extravasian

A

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)

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9
Q

why is the venular site ideal for modification of microvascular permeability

A
  1. low hydrostatic pressure
  2. large SA
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10
Q

why does oedema occur during extravasian

A

leakage of plasma proteins and fluids into extracellular space from:

endothelial damage and post capillary venule modulation

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11
Q

agents that increase venular permeability

A

contract pore proteins by elevating Ca2+

Histamine - H1 receptors

Bradykinin

Leukotriene C4 and D4 and platelet activating factor (PAF)

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12
Q

agents that decrease venular permeability

A

relax pore proteins by cyclic AMP

ß2-adrenoceptor agonists - Terbutaline, Salbutamol relaxation of contractile proteins (anti-inflammatory like effect)

PGI2

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13
Q

what is the ‘TRIPLE RESPONSE’ in the SKIN- Chemical irritant/bee sting

A
  1. initial flush in the area of damage- release of histamine from mast cells and vasodilation
  2. 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
  3. 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.

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14
Q

what do oral anti-histamines do

A

reduce magnititude of histamine-induced temp change but does NOT abolish the response.

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15
Q

what happens to microcirculation in intermediate (>2 hour) extravasion?

A

release of TNFa and activation of complement

  • attracts neutrophils to area

Activation of vascular endothelium by cytokines and release of the interleukin-8

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16
Q

cell adhesion molecules

A
17
Q

neutrophil dependent extravasion

A

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.

18
Q

what does the attraction of neutrophils lead to in terms of large Mr substances?

what do these all lead to?

A
  1. upregulation of phospholipase A2 and induction of cyclooxygenase-2 (COX-2) - increased blood flow.
  2. release of IL-1 and TNF activates endothelial receptors
  • Cytoskeletal reorganization of endothelial contraction proteins. (where its present)
  • Long term change in endothelial cell permeability
  1. Production of endothelial-leukocyte adhesion molecules for monocytes

• (ICAM-1 & VCAM-1) and subsequent conversion into macrophages.

  1. Induction of Nitric Oxide Synthase II (upregulated during inflammatory), I normally present

Major vasodilator

• Cytokines produced by macrophages (TNFa and IL-1) induces Ca2+-independent nitric oxide synthase (NOS II) in macrophages and vascular smooth muscle to produce NO

prolonged increase in local blood flow and swelling associated with inflammation