What is acute inflammation?
A basic pathological process
Its a non specific initial reaction to tissue damage
Stereotyped irrespective of the aetiology - no matter what tissue or what kind of damage the response is the same
What are the 2 causes of inflammation?
1) Tissue death
What is a pyogenic bacteria?
Bacteria that on infection cause acute inflammation
What does the term pyogenic mean?
Acute inflammation is caused by a noxious agent, what 3 outcomes can come from acute inflammation?
1) Cells can regrow and heal by regeneration
2) Cells cannot regrow so the tissue has to be healed by repair
3) The damaging agent is not ‘sorted out’ by the acute inflammation so persists leading to chronic inflammation
What is suppuration and when does it occur in terms of the cycle of inflammation?
Suppuration is the formation of pus (accumulation of inflammatory cells)
Occurs if the damaging agent persists and can lead to further acute inflammation
What are the 3 purposes of acute inflammation?
1) Clear away dead tissues
2) Locally protect from infection
3) Allow access of immune system components
What are the 4 ‘cardinal signs’ of inflammation? (latin and english)
1) Heat - calor
2) Redness - rubor
3) Pain - dolor
4) Swelling - tumor
Why is redness a sign of inflammation?
Get vascular dilatation which leads to redness
Why is heat a sign of inflammation?
Due to vascular dilatation
Why is swelling a sign of inflammation?
Occurs because of inflammatory exudate in tissues
What are the 4 macroscocpic terms used to describe inflammation?
What is serous inflammation?
Acute inflammation characterised by the copious effusion of non viscous serous fluid
What is fibrinous inflammation?
Exudative inflammation where there is a disproportionately large amount of fibrin
What is purulent inflammation?
Inflammation accompanied by the formation of pus
What is pseudomembranous inflammation?
A form of exudative inflammation. Large amounts of fibrin in the exudate results in a membrane like structure covering the serous or mucous membrane of the acutely inflamed tissue
What are the 3 components of an acute inflammatory response? Describe them briefly
1) Vascular reaction - dilatation, changes in flow
2) Exudative reaction - formation of inflammatory exudate
3) Cellular reaction - migration of inflammatory cells out of vessels
Name 2 possible systemic effects of inflammation?
2) Acute phase reaction
Name a protein thats levels in the blood can quantify the severity of an infection?
C reactive protein made in the liver as part of inflammatory reaction
What 3 components are there to the vascular reaction component of acute inflammation?
1) Microvascular dilatation (there is an intial transient vasoconstriction but this is not clinically significant)
2) Initially increased flow then reduced flow (because of increased permeability, more goes in than comes out)
3) Increased permeability (mediated and non mediated)
Why may you get non mediated increased permeability of blood vessels in an acute inflammatory reaction?
Inflammation may be due to damage to endothelial cells of the vessels - in which case the damage would have caused increased permeability to the vessels
Name 5 of the inflammatory mediators which lead to increased vascular permeability?
1) Histamine - released from mast cells
4) Leukotriene B4
5) Complement compounds
What is acute inflammatory exudate made up of?
Protein rich - 50g/l
What are the 6 purposes of the inflammatory exudate?
1) Dilution of noxious agents
2) Transport to lymph nodes
3) Supply of nutrients - O2
4) Spread of inflammatory mediators
5) Spread of antibodies
6) Spread of drugs
How can the fibrinogen help to contain the infection locally?
Forms fibrinous mesh to contain whatever is causing the infection
What does the cellular reaction of acute inflammation consist of?
Accumulation of neutrophils in the extracellular space
In severe cases, accumulation of neutrophils, cellular debris and bacteria forms pus
Where are neutrophils produced?
In bone marrow
Why can an FBC showing neutrophils be clinically useful?
Increased number of neutrophils in acute inflammation - this can give us a quantitative value for the severity of the infection
How can neutrophils move to the sight of infection?
They are motile and amoeboid
Show directional chemotaxis - move along the concentration gradient of inflammatory mediators
What is the lifespan of a neutrophil?
Short - only hours in tissues
How do neutrophils fight infection?
Describe the both oxygen dependent and oxygen independent processes that neutrophils use to kill bacteria?
Engulph them by phagocytosis to form a phagolyzosome
Oxygen dependent - Enzyme myeloperoxidase makes free radicals which damage the macromolecules from which the bacteria are formed thus killing them
Oxygen independent - Involves specific enzymes such as lysozyme which break down bacteria cell walls
How do neutrophils move into the tissues in an acute inflammatory reaction?
Normal flow in the blood vessel is an axial stream so neutrophils dont come into contact with the endothelium
When vessels dilate and exudate moves out of the vessles the flow is slowed and neutrophils are no longer adhered to an axial stream, they come into contact with the endothelium and various ligand-receptor reactions take place
2) Rolling - adhesion (pavementing when the neutrophils line up on the endothelium)
3) Migration into the tissues (facilitated by the increased permeability of the vessels)
Name the 6 synthesised and 1 stored cell derived mediators of acute inflammation?
Stored 1) Histamine Synthesised 1) Prostaglandins 2) Leukotrienes 3) PAF 4) Cytokines (IL1, 8, TNFa) 5) NO 6) Chemokines
Name the 4 plasma derived mediators of acute inflammation?
1) Kinin system
2) Clotting pathway
3) Thrombolytic pathway
4) Complement pathway
Mediators of inflammation have a short half life, how are they disposed of?
Name the 5 mediators of inflammation that mediate vascular dilatation?
Name the 6 mediators of inflammation that mediate increased vascular permeability?
Name the 6 inflammatory mediators which lead to upregulation of adhesion molecules and therefore mediate neutrophil adhesion?
5) IL 1
Name the 3 inflammatory mediators involved in neutrophil chemotaxis?
2) IL 8
Why is it important to know the inflammatory mediators?
Important drug targets
Fibrinous necrosis in arteriolar walls is associated with what kind of hypertension?
Bradykinin is formed from a pre cursor by the action of which enzyme?
Give 3 examples of laboratory assessments of inflammation?
1) Full blood count
2) Erythrocyte sedimentation rate
3) Acute phase proteins
What is meant by the term resolution with regards to acute inflammation?
One of the possible outcomes of acute inflammation, occurs when minimal damage to tissues occurs, the noxious agent is dealt with and everything returns to normal - this is the ideal solution
What is meant by fibrosis in terms of as an outcome of acute inflammation?
Some tissue damage occurs and the tissue is not replaced by the same tissue, is just replaced by collagen - scar tissue - fibrosis of the organ, may get some deficit due to lack of functioning tissue
What is meant by the term suppuration in terms of as an outcome of acute inflammation?
An abscess forms, in this case you have got a marked neutrophil reaction with tissue damage
Why does acute inflammation sometimes become chronic inflammation?
This occurs when the damaging agent that caused the acute inflammatory reaction is not dealt with and thus persists leading to chronic inflammation