Acute Inflammation Flashcards
What are the clinical features of acute inflammation?
- Redness (dilation of small BVs)
- Heat (increased blood flow due to vasodilation + fever)
- Swelling (accumulation of fluid in ECM)
- Pain (Stretching of tissue due to oedema and mediators such as bradykinin and serotonin which stimulate pain receptors)
- Loss of function (Movement is inhibited by pain and severe swelling)
What are the vascular changes seen in acute inflammation?
- Vasodilation (Following transient vasoconstriction, vasodilation is caused due to histamine and nitric oxide on vascular smooth muscle)
- Increased vascular permeability (causes protein rich exudate to enter the extravascular tissue)
- Vascular congestion/stasis (slower blood flow and increased conc of chemical mediators)
- Endothelial activation (causing increased levels of adhesion molecules)
What causes increased vascular permeability?
- It is mediated by histamine, bradykinin and substance P which causes endothelial cell contraction and an increase in interendothelial spaces.
- Neutrophils can cause endothelial injury
What are the cellular process involved in acute inflammation
- Margination (Neutrophil polymorphs are first to migrate. White cells sit more peripheral in BV due to stasis).
- Rolling of cells (White cells stick and detach from the wall which is mediated by selectins and upregulated by interleukin 1 and TNF)
- Adhesion (stimulated in IL-1 and TNF and mediated by integrins. Chemokines also facilitate binding)
- Migration (Chemokines act on leucocytes to stimulate migration across endothelium)
- Chemotaxis (cells travel along chemical gradient of bacterial products, cytokines, complement and leukotriene B (produced by AA)).
How is an pathogen removed?
- Phagocytosis. (There is opsonisation of foreign material and engulfment via endocytosis. A phagosome is formed (vesicle containing foreign material) and it is fused with lysosomes containing enzymes to form a phagolysosomes. Material is destroyed and removed from the cell via pinocytosis)
How is an acute inflammatory response terminated?
- Removal of stimulus,
- Neutrophils have a short half life.
- Variation in cytokine stimuli.
- Neural impulses.
- Macrophages are activated to preform different functions
What are the mediators of inflammation, their principle source and their action
Cellular derived: Vasoactive amines (histamine and serotonin), arachidonic acid metabolites, nitric oxide, cytokines (interleukins and chemokines), leukotrienes, protstaglandins
Plasma protein derived (complement and coagulation and kinin systems)
What is the difference between exudate and transudate?
Exudate - Extra-cellular fluid with a high protein and cellular content.
Transudate - Extra-cellular fluid with a low protein and cellular content
What are the different types exudate?
- Serous - Usually transudate, found in pleural, pericardial and peritoneal spaces.
- Fibrinous exudate - exudate rich in fibrin often found on serosal surfaces like the meninges.
- Suppurative exudate - pus forming exudate rich in neutrophil polymorphs (found in abscesses)
- Haemorrhagic exudate - severe vascular injury or depletion of coag factors.
- Membranous exudate - Epithelium become coated in a membrane formed by fibrin, epithelial and inflammatory cells.
- Psudomembranous (ulceration) - surface exudate on mucosal/epithelial surfaces eg, c diff colitis
- Necrotising - high tissue pressure leading to vascular occlusion and thrombus. Necrosis and bacterial putrefaction leads to gangrene.
Describe features of mast cells
- Reside in tissue
- Granules are rich in histamine and heparin.
- Stimulated by injury, complement and IgE
- Role in allergy and anaphylaxis,
- Makes eicosanoids to propagate immune response
Describe features of macrophages
- Undergo chemotaxis,
- Synthesis TNF, IL-1 and IL-6,
- Can phagocytose pathogens,
- Antigen presenting cells. Link between innate and adaptive immune response
What forms the membrane attack complex?
Complement factors: C5b, C6, C7, C8 and C9
What are the beneficial effects of acute inflammation?
- Dilution of toxins by oedema fluid,
- Increase entry of antibodies and drug transport,
- Fibrin traps micro-organisms,
- Delivery of nutrients,
- Stimulation of immune response
What are the detrimental effects of acute inflammation
- Digestion of normal tissue,
- Swelling of tissue (problem if tissue is in a confined space, eg, epiglottitis)
- Inappropriate responses eg, type 1 hypersensitivity
What are the possible outcomes of acute inflammation?
- Resolution which occurs if there is minimal tissue damage, occurs in a tissue with regenerative capacity, if the cause is rapidly removed and if there is good vascular drainage.
- Healing by fibrosis which occurs after substantial tissue damage, in tissues incapable of regeneration and if there is abundant fibrin exudate.
- It can also progress to chronic inflammation if the stimulus persists or there is tissue destruction which leads to ongoing inflammation
