Session 2 - Inflammation Flashcards
What are the causes of inflammation?
Trauma
Hypersensitivity
Micro organisms
Other illnesses induce inflammation
What are the 5 clinical signs of inflammation?
Rubor - redness Calor - heat Tumour - swelling Dolor - Pain Loss of function
What happens in the vascular phase of inflammation?
- Vasoconstriction (seconds)
- Vasodilation (minutes), causing heat and redness
- Permeability increase, causing oedema
- Red cell stasis
What is Starlings Law?
Fluid movement controlled by balance between hydrostatic pressure (on vessel wall by fluid) and oncotic pressure (pressure exerted by plasma protein).
These pressures exist in the vessels and the interstitium.
What happens to Starlings Law during inflammation?
Vasodilation. - increased hydrostatic pressure in capillary.
More vessel permeability - Loss of plasma proteins into interstitium, increased interstitial oncotic pressure.
Causes tumour - oedema.
Why does stasis occur?
Movement of fluid out of the vessel, increases the viscosity of blood so reduced flow through vessel.
What are the two types of interstitial fluid?
Exudate - Occurs in inflammation, occurs due to increased vascular permeability so it is protein rich.
Transudate - Fluid loss due to increased capillary hydrostatic pressure or reduced capillary oncotic pressure. No change of vascular permeability.
- Occurs in heart failure/hepatic/renal failure
What are the 4 mechanisms of increased vascular permeability?
- Endothelial contraction
- Endothelial cytoskeleton reorganisation
- Direct injury eg chemical, toxic burns
- Leucocyte dependent injury
Not f8nished
What is the primary cell involved in the cellular phase?
Appearance?
Neutrophil - granulocyte, trilobed nucleus, eosinophilic.
How do neutrophils escape vessels?
- Margination - Statis causes neutrophils to line up at endothelium
- Rolling - Neutrophils roll along endothelium
- Adhesion - to endothelium
- Emigration - through blood vessel wall by diapedesis (collagenase digests basement membrane)
How to neutrophils adhere to endothelium?
- Selectins - endothelial surface, upregulated by chemical mediators.
- Integrins - On neutrophil surface, bind to receptors on endothelial surface. Can be made high affinity upon binding.
Integrins bind to selectins.
How do neutrophils move through the interstitium?
Chemotaxis - Move along a chemical gradient of chemoattractants.
Eg Bacterial peptides
Neutrophil cytoskeleton changes and produces pseudopod towards the area.
How to neutrophils recognise what they should be phagocytosing?
Opsonisation
Toxin covered with C3b and Fc (opsonins)
Receptors for the opsonins on neutrophil surface.
If bacteria has been encountered before, IgG is used as the opsonin.
How does oedema limit damage?
- Dilutes toxins
- Delivers plasma proteins to area of injury eg fibrin mesh limits spread of toxin, immunoglobulins
- Increased lymphatic drainage to deliver antigens to lymph nodes, inducing adaptive immune response
Why are neutrophils beneficial?
- Removal of toxins and pathogenic organisms
- Removal of necrotic tissue
- Release of chemical mediators stimulates and regulates further inflammation
- Stimulates pain to limit risk of further damage
What are the local complications of inflammation?
- Swelling - blockage of nearby tubes and ducts (intestines/bile duct)
- Compression of organs (pericarditis causes cardiac tamponade)
- Loss of fluid eg in burns
- Pain and loss of function eg muscle atrophy
What are the systemic complications of inflammation?
Fever - Endogenous pyrogens act on hypothalamus to alter baseline temperature control
NSAIDs - Non steroidal anti inflammatory drugs block production of prostaglandins (important pyrogens)
Leucocytosis - More WBC’s by IL-1 and TNF, useful to measure blood vessels
Acute phase response - CRP from inflammatory cells increases - malaise, reduced appetite, altered sleep, tachycardia
What is septic shock?
Widespread vasodilation due to an overwhelming infection. Huge release of chemical mediators.
Causes hypotension and tachycardia, multiple organ failure then death
Can be due to endotoxins produced by bacterial cells.
What happens after acute inflammation?
- Complete resolution
- Continuation causing chronic inflammation, abscess
- Chronic inflammation and fibrous repair, some tissue degradation
- Death
How does complete resolution occur?
All changes reverse - no margination of neutrophils, permeability and vessel calibre back to normal.
- Exudate drains away via lymphatics
- Fibrin degrades
- Neutrophils die, break up and get phagocytosed
- Damaged tissue regenerated
- Mediators are diluted/degraded
What are 5 features of acute inflammation?
- Immediate
- Short duration
- Innate
- Stereotyped
- Limits damage
What do neutrophils do?
Phagocytose pathogen and fuse with lysosomes, produce secondary phagolysosomes.
What chemical mediators cause vasodilation?
Histamine
Serotonin
Prostaglandins
Nitrous Oxide
What chemical mediators cause increase vascular permeability
Histamine
Bradykinins (vasoactive peptide)
Leukotrienes
C3a and C5a
