MoD - Acute inflammation Flashcards
What is acute inflammation?
This is a rapid response to an agent that aims to deliver mediators to a site of damage/infection. These mediators bring about a series of tissue changes.
What are the causes of acute inflammation?
Foreign bodies Immune reactions Infections Tissue necrosis Trauma Physical and chemical agents
What are the clinical signs of acute inflammation?
Rubor - redness
Color - heat
Tumour - swelling
Dolor - pain
What are the types of chemical mediators and what are their functions?
Vasoactive amines (histamine and serotonin) cause vasodilation + vascular permeability Vasoactive peptides (bradykinin) - vascular permeability + pain Complement - C3a and C5a - chemotaxis and punch holes in bacteria Cytokines/chemokines- interleukins, TNF
What do the mediators cause?
Tissue changes
- changes in blood flow
- fluid loss from vessels
- neutrophil migration
What changes in blood flow do mediators bring about?
Initial vasoconstriction of arterioles
Then vasodilation of arterioles and capillaries
Increased permeability of BV
Increased concentration of RBCs in small vessels - increased blood viscosity = STASIS
Which specific mediators cause vasodilation and increase vascular permeability?
Histamine - released from mast cells, basophils and platelets in response to physical damage or cytokines (from macrophages, B and T cells)
Serotonin
Bradykinin (also causes pain)
How is fluid flow across vessel walls determined?
The balance of hydrostatic pressure and oncotic pressure (colloid osmotic pressure)
What is oncotic pressure?
The pressure exerted by proteins (usually albumin) in blood plasma.
Usually tends to pull water in
What does arteriolar dilation lead to?
This leads to an increased hydrostatic pressure
What does an increase in vascular permeability lead to?
Endothelial cells contract and pull apart leaving gaps for plasma protein. And protein rich fluid moves into the interstitium.
What is exudate?
This is the protein rich fluid lost in oedema.
What is a transudate?
This is low protein fluid loss due to hydrostatic pressure imbalance.
E,g cardiac failure
What is oedema?
Net flow of fluid out of vessels
What are neutrophils?
First response to site of inflammation. They migrate through BVs and tissue space following chemical signals Ie. Interleukins, C5a (chemotaxis) Predominate cells in pus They also have a multi-lobed nucleus They are phagocytotic cells
What are the main proteins found in exudate?
Opsonins - coat foreign material - enhance phagocytosis
Complement - bacteria perforation
Antibodies - act as opsonins by binding to microorganism surface.
What are the stages in neutrophils reaches their target?
HINT - getting though BV wall
They are ‘summoned’ to place of injury by chemotaxis
They are activated by sodium and calcium entering the cell (sticky)
They marginate (line up near endothelial wall)
They roll along wall until they adhere (bind firmly)
Then they migrate through BV wall
They crawl though endothelium (diapedesis)
How do neutrophils act on their target?
They recognise bacteria via opsonins.
Then they phagocytose the bacteria
The membrane round the phagocyte forms a crater
Degranulation occurs in the phagosome
Killing by free radical injection or proteases occurs.
What is the difference between oxygen dependent killing and oxygen independent?
Ox dependent injects free radicals into phagosome
Ox independent uses proteases and phospholipases
Name some complications of acute inflammation
Damage to normal tissue from neutrophil substances
Obstruction of rubes from swelling of exudate
Loss of fluid
What are the systematic effects of acute inflammation
-Fever- thermostat turned up
-Leucocytosis - no of circulating leukocytes increase (esp neutrophils)
-Acute phase response - change in levels of plasma protein
Liver changes protein synthesis pattern
-Shock
How is acute inflammation resolved?
Mediators have a short half life so degrade quickly and are only present as long as the stimulus persists
Exudate is reabsorbed into the vessels or drained to lymphatics
Fibrin is degraded
Neutrophils undergo apoptosis (and are phagocytosed)
What is hereditary angio-oedema?
Autosomal dominant
Deficient in C1 esterase inhibiter (component of complement syst)
Patients have attack of rapid oedema of the dermis and intestine.
Gives abdominal pain
What is alpha 1 antitrypsin deficiency?
Autosomal recessive
Low level of alpha 1 antitrypsin (a protease inhibitor which deactivates neutrophil enzymes)
Proteases are realised unchecked so patients develop emphysema.
Hepatocytes also produce misfolded version which polymerises in the ER
What is chronic granulomatous disease?
This is when phagocytes are unable to produce the superoxide radical.
So they fail to kill bacteria and chronic inflammation occurs
