Flashcards in Pathology L14 Acute Inflammation 2 - Mediators Deck (19)
Why are the half-lives of mediators very short?
Natural decay (AA metabolites)
Active inactivation (complement)
What are the 2 main differences between cell derived and plasma mediators?
Cell derived mediators act alone and are active when secreted compared to plasma mediators which act in interacting cascades and require activation
What 2 main effects does histamine have in inflammation?
Vasodilation and increases permeability
What tissues produce serotonin as a vasoactive amine for inflammation?
Platelets and enterchromaffin cells
What are some examples of small specific granules and what are its main features?
Lysozyme, collagenase, histaminase, gelatinase, lactoferrin – needs low [agonist] for activation and usually released extracellularly
What are some features of azurophilic granules and give examples?
High [agonist] required for activation and released into phagosome – myeloperoxidases, proteases, acid hydrolases
When cyclooxygenases and lipoxygenases act on arachidonic acid, what 2 main molecule classes do each produce?
Cyclooxygenases – thromboxane and prostaglandin
Lipoxygenases – lipoxins and leukotrienes
What determines the AA metabolites produced in any particular cell?
Enzymes present in that cell
What inflammatory effects do leukotrienes C4, D4, E4 have?
Vasoconstriction and increased permeability
What are cytokines? Which are the two most prominent in inflammation?
Small proteins that deliver messages between cells – TNF and IL1
What are the 4 families of chemokines?
CXC, CC, C, CX3C
What are features of plasma derived mediators?
Circulate in blood stream in inactivated form
Mostly produced in liver
Multistep activation/amplification pathways
What are the 3 activation pathways of the complement cascade?
Alternative, Classical and Lectin
What are the 3 main outcomes of the complement cascade?
Recruitment of other cells (C3a, C5a – inflammation)
Opsonisation for phagocytosis C3b
Assembly of MAC and cell lysis (C5-9)
What are the 2 activation pathways of the coagulation cascade and how is each activated?
Intrinsic pathway – inactive Hagemann factor in circulation encounters collagen or basement membrane (negatively charged surface)
Extrinsic factor – caused by tissue injury and subsequent release of tissue factor
For the Kinin system, what effects are produced by the active molecule bradykinin?
Increased vascular permeability, vasodilation, PAIN, smooth muscle contraction
What is the basic sequence of events in the fibrinolytic system?
Plasminogen activator released from endothelium and leukocytes, cleavage of plasminogen to plasmin which acts as a protease to cleave fibrin and also C3 to C3a (fibrin split produces increases vascular permeability)
What cells produce nitric oxide?
Endothelial cells, macrophages, neurons