Acute inflammation Flashcards
What occurs during an inflammatory response?
- acute microvascular changes
- release of inflammatory mediators
- accumulation of inflammatory cells
- repair and healing
What triggers microvascular effects in an acute inflammatory response?
Local hormones and inflammatory mediators from cells and plasma in and around the vessels
What are some inflammatory mediators?
- histamine
- bradykinin
- nitric oxide
- eicosanoid- prostoglandins, leukotrienes
- neuropeptides
- cytokines- peptides e.g. interleukin-1
- complement, PAF
What vasodilators do cells/tissues release?
Endothelial cells- prostaglandins, nitric oxide
Inflammatory cells- prostaglandins, nitric oxide
Sensory nerves- neuropeptides e.g. CGRP
What causes oedema formation?
Direct: histamine, substance P, bradykinin, PAF, leukotrienes
Neutrophil dependent: agents that stimulate activation; neutrophils roll, then express cell adhesion molecules, adhere to the endothelium, extraversion, phagocytosis
What mediators lead to neutrophil accumulation in tissues?
Neutrophil activating agents: LTB4, C5a, IL-8
Endothelial adhesion molecule stimulants: TNF, IL-8
What is histamine and its action?
- formed from histidine
- major source: mast cells and basophils
- preformed, released in in allergic/hypersensitivity responses
- H1 receptors mediate: increased blood flow, increased microvascular permeability, itch
- H1 antagonists: mepryamine, chlorpheniramine
- involved in allergy, hay fever and skim irritations
What are the differences between first and second generation anti-histamines?
1st gen: sedating, short acting, rapid onset of action, more side effects
2nd gen: non-sedating, long acting, slow onset of action, less side effects
What are the roles of sensory nerves (C and Aδ fibres)?
- transmit sensory information to CNS/ initiate reflexes; nociception- pain and itch
- release neuropeptides including substance P, CGRP and VIP
- stimulants include: mechanical (pressure), temperature, chemical (mediators and capsaicin)
What is the effect of histamine when injected into human skin?
Triple response:
- local reddening
- oedema at site of intra-dermal injection
- axon reflex flare
- area of increased blood flow mediated by sensory nerves
What are the roles and effects of NO?
- regulation of blood flow/pressure
- host response to infection
- neurotransmitter
- pain
- can react to further yield cytotoxic radicals
What is the effect of bradykinin and its antagonists?
- a peptide formed in plasma by activity of enzymes on tissue fluid substrates called kininogens
- metabolised by angiotensin converting enzyme and carboxypeptidases
- present in nasal cavity during allergic rhinitic attacks
- B2 receptors are constitutive and mediate increased blood flow and microvascular permeability, nocieception, broncho-constriction and nasal blockage
- B2 antagonists inhibit effects of some angioedemas
- B1 receptors are induced in inflammation and mediate similar responses, especially pain
How is arachidonic acid metabolised?
- via cyclo-oxygenase to form prostaglandins and thromboxanes
- via lipoxygenase to form leukotrienes
Where are eicosanoid released and what are their effects?
- PGs synthesised by COX enzymes; LoTs sysnthesised by 5-lipooxygenase
- PGE2 & PGI2: released from endothelial cells and WBCs, mediate increased blood flow and hyperalgesia
- PGD2: released from mast cells, less potent
- LTC4 & LTD4: increase microvascular permeability, broncho-constrictors
- LTB4: chemotaxis, recruit neutrophils to inflammatory sites
What are the effects of NSAIDs?
Inhibit arachidonic acid metabolism via the cyclo-oxygenase pathway therefore inhibit prostaglandin generation
