L11- Acute inflammation Flashcards
What does the inflammatory response involve?
- Acute microvascular changes
- Release of inflammatory mediators
- Accumulation of inflammatory cells
- Repair and healing
What are examples of inflammatory mediators that trigger the microvascular effects?
- Nitric oxide
- Histamine
- Bradykinin
- Prostaglandins
- Neuropeptides e.g substance P
- Complement, PAF, Cytokines
Cause increased microvascular permeability (gaps between endothelial cells) leading to plasma extravasation and oedema formation
What is the microcirculation?
- Arteriole (blood flow changes)
- Capillaries (unimportant in inflammation)
- Venule (oedema formation and cell accumulation- lymphocytes)
What are the sources of vasodilators?
- Endothelial cells- prostaglandins, NO
- Inflammatory cells- prostaglandins, NO
- Sensory nerves acting on endothelium- neuropeptides
What are direct acting oedema mediators?
- Histamine
- Substance P
- Bradykinin
- PAF
- Leukotrienes
What are neutrophil dependent oedema mediators?
Agents that stimulate neutrophil activation causing neutrophils to adhere to endothelium
What are the neutrophil-endothelial cell interactions?
- Rolling of neutrophil along post-capillary venule
- Cell adhesion molecule expression (CAM)
- Adherence by flattening of neutrophil
- Extravasation by making gaps between endothelial cells
- Phagocytosis of bacterium
What are neutrophil activating agents?
• LTB4 • C5a • IL-8 • TNF Act on receptors on neutrophil's to stimulate them
What are endothelial adhesion molecule stimulants?
• TNF
• IL-1
Makes endothelial cells more adhesive so neutrophils can stick to them
What is histamine?
- Major inflammatory mediator
- Mast cells and basophils release
- Preformed and released in allergic/IgE hypersensitivity responses
- When IgE antibodies become cross-linked they activate the release of histamine by Ca2+ influx into cells
What do H1 receptors do?
- Found on endothelial cells
- Increased blood flow
- Increased microvascular permeability- oedema
- itch
What are 1st gen H1 antagonists?
• CHLORPHENIRAMINE
• DIPHENYDRAMINE
• PROMETHAZINE
sedating, short acting, rapid onset
What are the steps in histamine release?
- Histidine broken down into histamine by histidine decarboxylase
- Histamine stored in vesicles
- Allergic IgE mediated reaction causes degranulation
- Histamine acts on its receptors
What are the effects of histamine?
- Itching and pain
- Bronchoconstriction, nasal congestion
- Increases blood flow and vascular permeability leading to erythema, edema and flare (triple resp)
What are second gen H1 antagonists?
• LORATADINE • CETIRIZINE • TERFENADINE • ASTEMIZOLE non sedating, longer acting, slow onset, less side effects
What are sensory nerves?
- C fibres- slow
- A δ fibres- fast
- Transmit sensory info to CNS and initiate reflexes, noiception (pain and itch)
- Release neuropeptides
What are stimulants of sensory nerves?
- Mechanical (pressure)
- Temperature (cold and heat)
- Chemical (mediators and capsaicin)
What is nitric oxide?
Another inflammatory mediator
• Produced from arginine + O2 to produce citrulline + NO, mediated by nitric oxide synthase enzyme
What are the types of NOS?
Constitutive: • Endothelial- eNOS • Neurons- nNOS Inducible: • Macrophages- iNOS
What are the roles of NO?
- Regulation of blood flow and pressure (eNOS)
- Immune response (iNOS)
- Neurotransmitter, pain (nNOS)
- Radicals (cytotoxic)
What is bradykinin?
- Inflammatory mediator formed in plasma by activity of enzymes on tissue fluid substrates called kininogens
- Metabolised by ACE enzyme and carboxypeptidases
What to B2 receptors mediate?
• Increased blood flow and microvascular permeability
• Noiception (enhanced sensitisation of pain and itch)
• Bronchoconstriction and nasal blockage
*B1 receptors similar in inflammation
How are prostaglandins and thromboxanes produced?
Arachidonic acid breakdown by cyclo-oxygenase enzyme
How are leukotrienes produced?
Arachidonic acid breakdown by lipoxygenase enzyme
