Acute Inflammation 2: Mediators and Outcomes Flashcards
What are chemical mediators?
Chemicals involved in the communicator and transmission of information between cells. They are tightly regulated and short lived, and control the mechanisms of inflammation.
Chemical mediators are either ____ derived In precursor form) or _____ derived (preformed in lysosomal intracellular granules or newly synthesised).
Plasma or Cell
Cell derived inflammatory mediators are either pre-formed or newly synthesised. True or false?
True.
Cell derived mediators include:
- Histamine
- Prostaglandins
- Leukotrienes
- Platelet-activating factor
- Nitric oxide
- Cytokines, including chemokines
Plasma derived mediators include:
• Factor XII activated pathways: Factor XII (produced in the liver) is activated by contact with sub-endothelial basement membrane or interstitial collagen. When activated, it can then activate three plasma systems: o Fibrinolytic system o Kinin system o Coagulation cascade
• Complement system
hree activation pathways:
o Classic pathway
o Alternative pathway )
o Lectin pathway
Results in the formation of many chemical mediators (such as C3a and C5a which cause vasodilation via release of histamine; and C3b which is an opsonin) and the Membrane Attack Complex (which lyses microbes).
What is the complement system:
The complement system involves a cascade of proteolytic enzymes that circulate the plasma in an inactive form.
This cascade leads to the formation of a membrane attack complex, whereby the complex drills a hole in the bacterial cell walls, causing it to lyse osmotically and be destroyed.
What is the principle mediator of arteriolar vasodilation and increased venular permeability?
Histamine
____ and ____ are locally produced, short lived and do not circulate systematically. They are derivatives or arachidonic acid. _____ are responsible for Vasodilation and potentiating pain. ______ are responsible for chemotaxis, vascular permeability and smooth muscle contraction
Prostaglandins and Leukotrienes
____ has been shown to:
- Increase vascular permeability
- Increase leukocyte adhesion to endothelium as well as ______ and ______
- Boosts the synthesis of ____ and _____
PAF
Chemotaxis
Activation
Prostaglandins and Leukotrienes
Nitric Oxide has many pro inflammatory activities:
- Killing of microbes via the creation of reactive nitrogen species
- Potential to cause tissue damage
- Role in septic shock (why?)
What is an anti-inflammatory effect of NO?
the inhibition of leucocyte recruitment
What are two major cytokine mediators of inflammation?
IL-1
TNF-a
What are cytokines?
Polypeptides signalling molecules produced by activated macrophages that influence the behaviour of the cell that produces them, or nearby cells or, if entering the blood, cells through the body
What are the local effects of cytokines?
Inducing adhesion molecules on endothelial cells, to help leucocytes adhere and marginate.
induce production of chemokines (chemoattractive cytokines - IL-8 attracts neutrophils to inflamed tissue) as well as prostaglandins and NO.
Activate leucocytes to produce O2 radicals and lysosomal enzymes.
What are the systemic effects of cytokines?
prime mediators involved in the acute-phase response (the systemic effects of inflammation) – such as fever, appetite, neutrophilia (increase in number of neutrophils in the peripheral blood), synthesis of acute phase proteins by the liver.
They are the principal mediators of septic shock, as they can produce high amounts of NO.
What is common complication of acute inflammation?
- Tissue damage
- The irritant itself
- Ischemia
What are the toxic products of inflammatory cells?
Superoxide radicals –
supposed to be maintained within the phagolysosomes in leucocytes, but sometimes may leak out of leucocytes and damage any cells that it comes into contact with.
Neutrophils releasing lysosomal enzymes accidentally:
Collagenase – breaks down collagenase
Plasmin – breaks down fibrin
Elastase – breaks down elastin
All of the above mediators can contribute to causing liquefactive necrosis of the host tissue (ie. Suppuration, pus – debris, exudate, dead cells)
Toxic products of inflammatory cells released during phagocytosis include:
Neutrophil lysosomal enzymes- collagenase, elastase, plasmin (splits fibrin)
Superoxide radicals
Suppuration generally occurs in the presence of pyogenic bacteria that have peptides that posses an N-formlymethionine terminal amino acid that is strongly __________
Chemotactic for neutrophils
What is an abscess?
A localised collection of pus in an organ or tisse
How can abscesses be caused?
Pyogenic (‘pus-forming’ because of their formyl cell walls being strongly chemotactic in attracting neutrophils to cause pus
Obstructed drainage of infective material
What are some complications of abscesses?
- Pyaemia – when microorganisms enter the blood stream. This can cause multiple abscesses lodged by the circulation and lead to septic shock as massive amounts of IL-1 and TNF- α are produced.
- Empyema – when pus collects in a natural cavity (as opposed to the newly created cavity of an abscess).
What is the acute inflammation time course?
- Initially, there is a large burst of exudation due to the release of histamine and bradykinin, which is then sustained and then begins to decline.
- After an initial lag, the lymphatic flow matches the rate of exudation in the tissue to prevent any further swelling of the tissue
- Soon after this, there is the emigration of neutrophils (polymorphonucleocytes), which then die off after apoptosis.
- After a couple of days, the monocytes (which mature into macrophages in tissue) emigrate and dominate the response – which is important for ‘cleaning up’ the debris of the inflammatory response, as well as initiating healing by repair if necessary.
