Acute Inflammation Flashcards
(40 cards)
Define acute inflammation
Definition: any inflammation that has a fairly rapid onset, quickly becomes severe, and is usually manifested for only a few days, but that may persist for even a few weeks; characterized histologically by edema, hyperemia, and inflitrates of polymorphonuclear leukocytes.
Fundamental response maintaining integrity of organism involving a series of protective changes occurring in living tissue as a response to injury
What are the 5 cardinal signs of inflammation?
- Rubor - redness
- Calor - heat
- Tumor - swelling
- Dolor - pain
- Loss of function
All of these explained by the sequence of pathological events taking place
What is the aetiology of inflammation?
Microorganisms Mechanical Chemical Physical Dead tissue Hypersensitivity
What is the microcirculation?
Circulation of blood in smallest vessels e.g.:
• Capillary beds, fed by arterioles and drained by venules
• Extracellular “space” and fluid and molecules within it
• Lymphatic channels and drainage
What force controls the flow of fluid over membranes?
Starling forces control flow (fluid flux) across membrane
Q = LpS{(Pc - Pi) - σ(Πp - Πi)}
What is the starling equation?
The Starling equation is an equation that illustrates the role of hydrostatic and oncotic forces (the so-called Starling forces) in the movement of fluid across capillary membranes
Describe the local changes vessel radius and flow during inflammation and the signs of its occurrence
- Transient arteriolar constriction - few moments, protective (white)
- Local arteriolar dilatation - active hyperaemia (local, red)
- Relaxation of vessel smooth muscle - autonomic NS or mediator derived
Called the “Triple Response” - flush, flare, wheal
What is Poiseuille’s law?
Poiseuille’s law - flow is proportional to radius to the power of four
• Q = ΔP x Πr4/8ηL
• Increased arteriolar radius causes increased local tissue blood flow
• Radius controls blood flow!
What is exudate?
Exudate - fluid rich in protein e.g. plasma which includes immunoglobulin and fibrinogen that seeps out of blood vessels or organs during inflammation
Describe the phases of neutrophil emigration
- Margination - neutrophils move to endothelial aspect of lumen
- Pavementing - neutrophils adhere to endothelium
- Emigration - neutrophils squeeze between endothelial cells - active process - to extravascular tissues
- Diapedesis – leukocyte extravasation (not neutrophils, later effector cells)
Describe the benefits of acute inflammation reactions
• Rapid response to non-specific insult • Cardinal signs and loss of function – Transient protection of inflamed area • Neutrophils destroy organisms and denature antigen for macrophages • Plasma proteins localise process • Resolution and return to normal
What are the 5 possible outcomes of acute inflammation?
Resolution Suppuration - the process of pus forming Dissemination Organisation - replacement with granulation tissue Chronic inflammation
What is the role of neutrophils in inflammation?
• Mobile phagocytes
– Recognise foreign antigen
– Move towards it - chemotaxis
– Adhere to organism
• Granules possess oxidants (e.g. H2O2) and enzymes (e.g. proteases)
• Release granule contents
• Phagocytose and destroy foreign antigen
What is pus?
- Neutrophils die when granule contents released
* Produce a “soup” of fluid, bits of cell, organisms, endogenous proteins - pus
What helps to localise inflammation?
Fibrinogen in exudate forms fibrin to make a clot
What cell surface mediators are useful in inflammation?
ICAM-1 - on endothelial cells, help neutrophils stick
P-selectin - on endothelial cells, interacts with neutrophil surface
Describe some useful molecules released during inflammation
- Histamine
- 5-hydroxytryptamine (serotonin)
- Prostaglandins (arachidonic acid metabolites via lipoxygenase pathway)
- Leukotrienes (arachidonic acid metabolites via cyclo-oxygenase pathway)
- Omega-3 polyunsaturated fatty acids
- Platelet-activating factor (PAF)
- Cytokines and chemokines (eg TNFα, IL-1)
- Nitric oxide (NO)
- Oxygen free radicals (H2O2, OH-, O2-)
What are the useful effects of histamine?
– Preformed in mast cells beside vessels, platelets, basophils
– Released as a result of local injury; IgE mediated reactions
– Causes vasodilatation, increased permeability
– Acts via H1 receptors on endothelial cells
What are the useful effects of serotonin (5-HT)?
– Preformed in platelets
– Released when platelets degranulate in coagulation
– Vasoconstriction
What are the useful effects of prostaglandins?
– Many cells (endothelium and leukocytes)
– Many promote histamine effects and inhibit inflammatory cells
– Thromboxane A2 promotes platelet aggregation and vasoconstriction – the opposite effect to PGD2, PGE2, etc
– Latter: effectiveness of non-steroidal anti-inflammatory drugs
What are the useful effects of leukotrienes?
– Neutrophils especially
– Vasoactive - dynamic effect on vessels to increase permeability and constrict smooth muscle
What are the useful effects of omega 3 polyunsaturated fatty acids?
– Decrease synthesis of arachidonic acid derived inflammatory mediators
What is the useful effect of platelet activating factor (PAF)?
– Cell membranes of activated inflammatory cells
– Reduces permeability by enhancing platelet degranulation at site of injury
What are the useful effects of cytokines and chemokine?
– Small molecules produced by macrophages, lymphocytes, endothelium in response to inflammatory stimuli
– Attract inflammatory cells and activate other immune cells
