Acute Inflammation 2 Flashcards
What is inflammation of the: 1. peritoneal cavity 2. meninges 3. appendix 4 lungs 5. pleural cavitiy called?
- peritonitis
- meningitis
- appendicitis
- pneumonia
- pleurisy
most follow rule ‘structure’-itis but there are some exceptions (e.g. 4&5)
What do neutrophils do?
They’re mobile phagocytes (recognise foreign antigen, move towards it by chemotaxis, adhere to organism).
They have granules containing oxidants (e.g. hydrogen peroxide) and enzymes (e.g. protases) which they release to destroy foreign antigens.
What is chemotaxis?
Neutrophils detect chemicals released by foreigners and move towards them by move up the concentration gradient on the chemicals.
What happens to neutrophils when they release the contents of their granules?
Neutrophils die.
This produces pus (mixture of fluid, bits of cells, organisms, endogenous proteins)
Name two plasma proteins involved in the inflammatory response.
Fibrinogen and immunoglobulins.
What would happen if the pus extends onto other tissues?
Inflammation would be progressed.
What are the role of immunoglobulins in inflammation?
Immobilise specific antigens - humour immune response.
What is the role of fibrinogen in inflammation?
It is a coagulation factor. It cleaves and polymerises to form fibrin which clots the exudate localising the inflammatory response.
Give examples of mediators in acute inflammation.
Molecules on endothelial cell surface membrane.
Molecules released from cells.
Molecules in the plasma.
Give examples of the collective effects of mediators.
Vasodilation Increased permeability Neutrophil adhesion Chemotaxis Itch and pain
** Give examples of cell surface mediators.
ICAM-1 - helps neutrophils stick
P-selectin - interacts with neutrophil surface
Why is histamine released during inflammation?
Mast cell degranulation is a component of inflammation and histamine is contained within these granules.
Molecules released from cells: histamine
preformed in mast cells besides vessels, platelets, basophils
released as result of local injury, IgE mediated reactions
Causes vasodilation, increased permeability
acts via H1 receptors on endothelial cells.
Molecules released from cells: 5-hydroxytryptamine (serotonin)
Preformed in platelets
Released when platelets degranulate in coagulation
Causes vasoconstriction
Molecules released from cells: prostaglandins (arachidonic acid metabolites via lipoxygenase pathway)
Released from many cells (endothelium + leukocytes)
Many promote histamine effects and inhibit inflammatory cells
Thromboxane A2 promotes platelet aggregation and vasconstriction - opposite effect of PGD2, PGE3 etc.
Molecules released from cells: leukotrienes (arachidonic acid metabolites via cyclo-oxygenase pathway)
Released from neutrophils especially
Vasoactive - dynamic effect on vessels to increase permeability and constrict smooth muscle
Molecules released from cells: omega-3 polyunsaturated fatty acids
Decrease synthesis of arachidonic acid derived inflammatory mediators
Molecules released from cells: platelet-activating factor (PAF)
Released from cell membranes of activated inflammatory cells
Reduces permeability by enhancing platelet degranulation at site of injury
Molecules released from cells: cytokines and chemokines (e.g. TNFalpha, IL-1)
Small molecules produced by macrophages, lymphocytes, endothelium in response to inflammatory stimuli
Attract inflammatory cells
Molecules released from cells: nitric oxide (NO)
Released by various cells
Smooth muscle relaxation, anti-platelet, regulates leukocyte recruitment to inflammatory focus
Molecules released from cells: oxygen free radicals (H2O2, OH-, O3-)
Released by neutrophils on phagocytosis
Amplify other mediator effects
What are the four enzyme cascades involved in inflammation?
Blood coagulation pathways
Fibrinolysis
Kinin system
Complement cascade
What are the role of blood coagulation pathways?
Clots fibrinogen in exudate
What is fibrinolysis?
Break down of a fibrin clot, helping to maintain blood supply
Fibrin breakdown products are vasoactive
What is the kinin system?
It consists of blood proteins that play a role in inflammation, blood pressure control, coagulation and pain, e.g. bradykinin stimulates nerves so you feel pain at the site of inflammation
What is the role of complement cascade in inflammatory response?
Ties in w/ immune system
Active components stimulate increased permeability, chemotaxis, phagocytosis, cell breakdown
What are the immediate systemic effects of inflammation?
Pyrexia (raised temp) Fell unwell (malaise, anorexia, nausea, abdominal pain & vomiting in children Neutrophilia (raised WBC count - bone marrow makes and releases)
What are some of the longer term effects of inflammation?
Lymphadenopathy (regional lymph node enlargement due to immune response)
Weight loss - catabolic process
Anaemia
One of the outcomes of acute inflammation is suppuration, what is this?
Pus formation with a pyogenic membrane surrounding this pus
What does pus consists of?
Dead tissue, organisms, exudate, neutrophils, fibrin, red cells, debris…
What does the pyogenic membrane consist of and what is its function?
Capillary sprouts (little vessels growing into inflamed area), neutrophils, fibroblasts Walls of puss - preventing spread
What is an abscess?
A collection of pus (suppuration) under pressure
Can be single locule or multiloculated
Has a point and discharges
Collapses - healing and repair
When would a multiloculated abscess form?
If the pus bursts through pyogenic membrane and forms new cavities
What is an empyema and give examples of where one might happen?
A collection of pus in a hollow viscus
E.g.s - gall bladder, pleural cavity
What is pyaemia?
Blood poisoning caused by the spread of pus into the bloodstream
Another outcome of acute inflammation is organisation, what does this involve?
Granulation tissue
Healing and repair
Leads to fibrosis and formation of scar
What is granulation tissue?
A 'universal patch' Formed of: New capillaries (angiogenesis) Fibroblasts & collagen Macrophages
Another outcome of acute inflammation is dissemination, what does this involve?
Spread to bloodstream - patient ‘septic’
Define bacteraemia
Bacteria in blood
Define septicaemia
Growth of bacteria in blood
Define toxaemia
Toxic products in blood
What is cardiac output (CO) and how is it mathematically worked out?
Volume of blood pumped by the heart per min.
CO = stroke volume (SV) x heart rate (HR)
What is stroke volume?
Amount of blood ejected by left ventricle in one contraction
What is systemic vascular resistance (SVR)?
The resistance the left ventricle must overcome to pump blood through the systemic circulation
As peripheral BVs constrict, SVR increases
How can you mathematically work out blood pressure (BP)?
BP = CO x SVR
What are the effects of systemic infection?
Shock - inability to perfuse tissues
What are some symptoms of early septic shock?
Peripheral vasodilation Tachycardia (high HR) Hypotension (low BP) Often pyrexia Sometimes haemorrhagic skin rash
Explain what brings about the symptoms of septic shock.
Systemic release of chemical mediators from cells into plasma
- mediators cause vasodilation (therefore loss of SVR, so BP drops)
Results in catecholamine release
Tachycardia to maintain CO as increased HR compensates (CO = SV x HR)
Bacterial endotoxin released (interleukin-1 released acts on hypothalamus = pyrexia)
Activation of coagulation (disseminated intravascular coagulation, vasoactive chemical causes vasodilation, haemorrhagic skin rash)
When you cleave fibrinogen what does the by-product act as?
Causes vasodilation
Eventually, when the HR is insufficient to maintain CO, what happens?
SVR low, BP falls
Reduced perfusion of tissues causing tissue hypoxia and loss of cell tissue and organ function
What is the outcome of septic shock?
Rapidly fatal
Tissue hypoxia - cell death
Haemorrhage
How should septic shock be dealt with?
Awareness and early recognition are important
Young people can compensate for some time
But anyone w/ septic shock must be admitting to hospital & ICU
