Inflammation Flashcards
What are the 5 cardinal signs of inflammation?
Heat=callor Redness = rubor Swelling = tumor Pain = dollor loss of function
What type of immune response is inflammation?
Innate immune response - non-adaptive
What is the inflammation initiated by?
Pattern recognition receptors - recognise pathogens by their pathogen associated molecular patterns (sugar. molecules on bacteria). e.g. Toll like. receptors - specific stimulus can evoke different inflammatory response
What events is inflammation characterised by?
Cellular & vascular
initial cellular and late cellular
What incorporates the initial cellular events?
Sentinel cells activate mast cells, dendritic, macrophages to release cytokines. - trigger response
Mast cells release histamine activated by IgE antibody and c3a/c5a
Endothelial cells releasing pro inflammatory mediators to cause vasodilation. e.g. prostaglandins, NO
Adhesion molecules for leukoytes
What incorporates the vascular events?
Redness/swelling/heat (due to blood/fluids).
Proteolytic cascades - factor 12a from plasma stimulates pro inflammatory products that activate complement cascade C1-9. Coagulation, fibrinolytic and kinin
Generate mediators that stimulate components of the response e.g. C3a/c5 stimulating mast cells to release histamine.
What incorporates the later cellular events?
Monocytes differentiate into macrophages to eat cell debris. (after neutrophils)
Is inflammation a symptom or cause of disease?
Symptom
What happens when the inflammation in the cellular & vascular events fails to resolve?
chronic inflammation
Explain the anti-pyretic effects of NSAIDS
There is prostaglandin E2 formation in the hypothalamus triggered by fever causing pathogens. NSAIDs reduce/prevent PG production to reduce body temp (but do not affect normal body temp)
Explain the analgesic effects of NSAIDS
Inhibition of COX1/2 Reduce the formation of prostaglandins that sensitise nociceptors as inhibited COX2 enzymes.
(prostaglandins usually sensitise the pain produced by inflammatory mediators e.g. bradykinin)
Explain the anti-inflammatory effects of NSAIDS
Inhibit COX1/2 enzymes. Reduce inflammation produced by prostaglandins esp those produced by COX2.
- Reduce vasodilation caused by PGE2/PGI1
- reduce swelling and vascular permeability/wheal/oedema
- BUT only reduce the components of the inflammatory response dependent upon prostaglandin formation
What is a limit to the anti-inflammatory effects of NSADIS?
only reduce the components of the inflammatory response dependent upon prostaglandin formation
What side effects can non-selective COX inhibitors give and why?
GI effects because gastric COX1 usually produces prostaglandins that reduce acid secretion and promote mucosa formation. If inhibiting = mild get dyspepsia, diarrhoea, If severe can be bleeding, ulcers
Bronchospasm in some pts e.g. asthma as prostaglandins have a role in bronchodilation
Skin reactions
Nephropathy as reduction in renal blood flow due to reduced prostaglandins
Which COX inhibitors cause cardiovascular s/e?
COX2 selective possibly due to reduced PGI2 production or chance in the balance of PGI2 and thromboxane A2 production
What is the risk of NSAIDS in 3rd trimester of pregnancy?
Pulmonary hypertension in the foetus
What are NSAIDS used in caution with/ci?
Contraindicated in pts with GI disorders
C/I in people with renal failure
COX2 contraindicated in cardiac failure
What are some indications of naproxen
Pain & inflammation in rheumatic disease
Musculoskeletal pain
Dysmenorrhoea
Acute gout
What are some indications of ibuprofen?
Pain &inflammation in rheumatic disease Mild to moderate pain dysmenorrhoea post-op analgesia migraine dental fever in children post immunisation pyrexia
What are some indications of diclofenac?
POM - pain and inflammation in rheumatic disease
acute gout
post op pain
What subtype of prostaglandin predominates in inflammation?
PGE2
What are the roles of prosaglandins?
Vasodilatiton
fever
pain (sensitisers)
Inflammatory response
What are the effects of histamine?
Flush (arterial vasodilation)
Redness, wheal, oedema, swelling, flare (sensory nerve induced vasodilation CGRP)
- inflammation
What are the inflammatory effects of histamine mediated by?
Stimulation of h1 receptor -
- constricts bronchial and GI smooth muscle
- dilates blood vessels by stimulating endothelial cells
- itch usually associated with wound healing
