Inflammation Flashcards
What is inflammation? What are the signs of inflammation?
It is the body’s defence response to:
- invasion – pathogens (disease-causing), allergens (non-disease)
- injury - heat, ultraviolet, chemicals
signs of inflammation
calor - increased blood flow, warmth/heat
rubor - increased blood flow, redness
dolor - pain, activation of sensory nerves
tumor - swelling, increased post capillary venule permeability
function laesa - loss of function
What are NSAIDS?
NSAIDS are Non-Steroidal Anti-inflammatory Drugs
- analgesic (prevention of pain)
- anti-pyretic (lowering of raised temperature, fever)
- anti-inflammatory (decrease an immune response)
What are NSAIDS used to treat?
NSAIDS are used to treat:
- low grade pain (chronic inflammation, e.g. arthritis)
- bone pain (cancer metastases)
- fever (associated with infections)
- inflammation ( symptoms- oedema, redness, itch)
What are local hormones?
local hormones are also known as autocoids
- produced in response to a wide range of stimuli
- synthesised or released only as and when required
- local release for local action
- inactivated locally to minimise systemic effects
What is histamine? How is it synthesised, stored and released?
synthesis
- synthesised from histidine amino acid by histidine decarboxylase
- metabolised by imidazole-N-methyltransferase (INMT) and diamine oxidase
stored and released from
- mast cells, which express receptors for IgE on cell surface (connective tissues)
- basophils (blood)
- neurons in brain
- histaminergic cells in gut = histamine secreting cell
pre-made, ‘ready-to-go’ in secretory granules composed of heparin and acidic proteins
How is histamine release stimulated by allergens?
mast cells expresses IgE and its receptors on its surface
- allergens crosslink with IgE on the mast cell surface
- crosslink causes release of mediators (histamine) from the mast cell
= degranulation of the mast cell/release of vesicles is calcium dependent
What is the triple vascular response?
redness - depends on chemical mediator
flare
wheal - raised or swollen marks left behind
What are the types of histamine receptors?
H1, H2, H3 and H4
- are all G protein coupled receptors
H1 and H2 are clinically important
What is the effect of stimulating H1 and H2 receptors?
cardiovascular
- dilates arterioles and reduces TPR = H1
- increased permeability of post capillary venules = H1
- increased HR = H2
- decrease blood pressure = H2
non-vascular smooth muscle = airways, gut
- contraction = H1 (bronchoconstriction)
algesia
- pain, itching, and sneezing caused by stimulation of sensory nerves = H1
gastric acid
- increased secretion = H2
associated exocrine secretions
- increased due to increased blood flow
What are the physiological effects of histamine (via the stimulation of histamine receptors)?
- gastric acid production
signal sent to the brain from the gastric vagus nerve
stimulates gastrin secretion by the G cells
gastrin
- can act on/bind to the histamine secreting cell (HSC) to stimulate histamine release . histamine can bind to H2 receptors on the parietal cell simulating gastric acid secretion
- can also act directly on the parietal cell to stimulate gastric acid release
acetylcholine
- can act on/bind to the histamine secreting cell (HSC) to stimulate histamine release . histamine can bind to H2 receptors on the parietal cell simulating gastric acid secretion
- can also bind to muscarinic receptors on the parietal cell stimulating gastric acid secretion
What are the physiological effects of histamine (via the stimulation of histamine receptors)?
- gastric acid inhibition
prostaglandin E2
- can inhibit the parietal cell and stop gastric acid secretion
- can stimulate the mucus secreting cell to produce mucus = protects lumen of the stomach from acdo
- can promote bicarbonate secretion = neutralises gastric acid
What are the effects of H1 and H2 antagonists? What are examples of H1 and H2 antagonists? What are their effects and side effects?
H1 antagonist
- 1st generation = mepyramine
- 2nd and 3rd generation = terfenadine
reduces inflammatory responses = treats acute inflammation
- anti-emetic (treat motion sickness) or anti-muscurinic ( have atropine like effects)
H2 - cimetidine ranitidine - reduce/inhibit gastric acid secretion = increase breakdown of histamine - mental confusion, dizziness
What are the lipid mediators of inflammation?
collectively known as eicosanoids
are split into
- cyclo-oxygenases pathway which includes prostanoids
= prostanoids are prostaglandins and thromboxanes
- lipo-oxygenases pathway which includes leukotrienes and lipoxins
What are eicosanoids? Why are they important?
are lipid mediators of inflammation
are targets of anti-inflammatory drugs
How are prostanoids generated?
are not ready to go unlike histamine
are generated from arachidonic acid
- arachidonic acids are generated from phospholipids
