Acute Inflammation Flashcards
Define acute inflammation
Physiological response to tissue damage.
A series of protective changes occurring in living tissue as a fundamantal response to injury to maintain the integrity of the organism
What are the cardinal signs of inflammation?
Rumor - redness
Calor - heat
Tumour -swelling
Dolor - pain
Loss of function
What are the causes of acute inflammation?
Microorganisms
Trauma
Chemical
Physical - extreme conditions such as heat, cold, radiation
Necrosis (Dead tissues irritating adjacent tissues)
Hypersensitivities
Features of the process of acute inflammation
Series of microscopic events
Localised to affected tissue
Takes place in microcirculation
Results in the cardinal signs
What is microcirculation?
Capillary beds (fed by arterioles and drained by venules)
Extracellular space and fluid and molecules within
Lymphatic channels and drainage
What creates dynamic balance?
Hydrostatic and colloid osmotic pressures
Compartments and physical constants
Define hydrostatic pressure
Pressure exerted by a fluid
Define oncotic pressure
Pressure exerted by proteins in the blood vessel plasma
What are the step in acute inflammation pathogenesis?
- Change in vessel radius
- Change in the permeability of the vessel wall - exudation - endothelium becomes more or less permissive which changes the amount of fluid that can go through the membrane
- Movement of neutrophils from the vessel to the extravascular space
What is exudation?
Plasma (fluid) moves from the capillary(vessel) to the extracellular space
What is exudate?
The fluid that is leaked - rich in plasma proteins (immunoglobulin and fibrionogen)
What does increased arteriolar radius cause?
Increased local tissue blood flow which causes:
Redness - Rubour
Heat - Calor
Features of increased permeability
Localized vascular response occurring in the microvascular bed
Endothelial leak - fluid and protein not held in the vessel lumen
Locally produced chemical mediators
What is the effect of exudation?
Oedema - accumulation of fluid in the extravascular space - is formed
There is swelling, pain and reduced function
What is the effect of exudation on blood viscosity?
Increased viscosity - rate of blood slows down aka stasis
Describe the structure of the blood flow in inflammation
RBC’s aggregate in the center of the lumen and neutrophils are found near the endothelium
How are the components of blood laid out?
Plasma sits on the outside because it is the smallest
The erythrocytes, the red cells are the next layer.
Then the white cells, particularly neutrophils in the centre.
What is the most important cell in the flow in inflammation?
Neutrophil (polymorphonuclear leukocyte)
What do we see in flow in inflammation?
Loss of nromal laminar flow
Red cells aggregate in the centre of the lumen
Neutrophils found near endothelium
What are the phases of emigration of neutrophils?
Margination - neutrophils move to the endothelial aspect of the lumen
Pavementing - neutrophils adhere to the endothelium
Emigration - neutrophils squeeze between endothelial cells - active process - to extravascular tissues
What does diapedesis mean?
Passage of blood cells through the intact walls of the capillaries, typically accompanying inflammation.
What are the benefits of acute inflammation?
Rapid response to non-specific injury
Protection in the inflamed area from cardinal signs
Neutrophils destroy organisms and denature antigens for macrophages
Plasma proteins localise process
Resolution and return to normal
What are the outcomes of acute inflammation?
Resolution
Suppuration - pus formation
Organization -tissue growth
Chronic infection
Name inflammation at the following sites:
Peritoneal cavity
Meninges
Appendix
Lungs
Pleural cavity
Peritonitis
Meningitis
Appendicitis
Pneumona
Plearisy
What do neutrophils do?
Recognise foreign antigen and move towards it - chemotaxis
Adhere to the organism
They are mobile phagocytes
Phagocytose and destroy the foreign antigen
What do the granules that contain neutrophils release the contents of?
Possess oxidants - H202 and enzymes (proteases)
When does a neutrophil die?
When granule contents are released
What is pus?
Produced by neutrophils - its a fluid made up of bits of cells, organisms, endogenous proteins
What is fibrinogen?
A plasma protein - coagulating factor forming fibrin which clots exudate, localises inflammatory process
What plasma protein is responsible for humoural immune response?
Immunoglobulins
What does humoural mean?
Relates to the immune response that involves the release of antibodies in circulating bodily fluids
Where are the mediators of acute inflammations?
Molecules on endothelial cell surface membrane - released from cells, molecules in the plasma
What are endothelial cells?
Linings of the walls of blood vessels
What the collective effects of mediators?
Vasodilation
Increased permeability
Neutrophil adhesion - mediators from different cells adhere because of their mediators
Chemotaxis
Itch and pain
Describe the action of adhesion molecules that appear on endothelial cells
Help neutrophils stick
ICAM - 1
Describe the function of P-Selectin
Interacts with neutrophil surface
What releases histamine?
Mast cells beside vessels, platelets, basophils
When is histamine released?
As a result of local injury
What is the effect of histamine?
Vasodilation, increases permeability, acts via H1 receptors (histamine receptors) on endothelial cells
What is another name for serotonin?
5 - hydroxytryptamine
Where is seratonin released from?
Platelets, when they degranulate in coagulation
Vasoconstriction - to keep useful materials in the correct place
What are the immediate systemic effects of acute inflammation?
Pyrexia - endogenous pyrogens from white blood cells act centrally
Feel unwell - malaise, anorexia, nausea, abdominal pain, vomiting in chilrdren
Neutrophilia - raised WBC count
What are the long term effects of inflammation?
Lymphadenopathy - lymph node enlargements
Weight loss - catabolic process
Anaemia
Describe what suppuration is
Pus formation
Pyogenic membrane surrounds pus (capillary sprouts neutrophils, fibroblasts - walls off pus)
What is an abscess?
Collection of pus under pressure
What is a multiloculated abscess?
Pus burts through the pyogenic membrane - forms new cavities
What is empyema?
Pus in a hollow viscus (gall bladder, pleural cavity)
What is pyaemia?
Discharge of pus to the blood stream
What is organisation?
Healing and repair - leads to fibrosis and formation of scar
Granulation tissue characteristic
What is granulation tissue?
Universal patch
It is formed of new capillaries
Fibroblasts and collagen
Macrophages
Describe the outcome of dissemination
Spreads to the bloodstream - patient is now described as septic
What is the difference between bacteraemia and septicaemia?
Bacteria in blood versus the growth of bacteria in blood
What is toxaemia?
Toxic products in the blood
How do you calculate cardiac output?
Stroke volume multiplied by heart rate
How can you calculate blood pressure?
Cardiac output multiplied by systemic vascular resistance
Define SVR
An index of arteriolar constriction throughout the body, calculated by dividing the blood pressure by the cardiac output.
What is the effect of systemic infection?
Shock - inability to perfuse tissue
What is the clinical picture of early septic shock
Peripheral vasodilation
Tachycardia
Hypotension
Often pyrexia
Sometimes haemorrhagic skin rash - blood vessels leaking
What is the effect of bacterial endotoxin?
Interleukin- 1 is released - acts on hypothalamus - pyrexia
What is the effect of prostglandins? (archidonic acid metabolite)
Histamine effects and inhibit inflammatory cells
Thromboxan A2 - promotes platelet aggregation and vasoconstriction
What is a leukotriene? (archidonic acid metabolite)
Any substance which is derived from a leucocyts (white blood cell)
Are leukotrines vasoactive?
Yes, they increase permeability and constrict smooth muscle
What is the effect of omega 3 polyunsaturated fatty acids?
Decreases synthesis of archidonic acid derived inflammatory mediators
What is the function of NO?
Released by various cells.
Responsible for smooth muscle relaxation, anti-platelet, regulate functional activity, growth and death of many cell types including macrophages, T lymphocytes, antigen presenting cells, mast cells, neutrophils and natural killer cells.
It regulates leukocyte recruitment to inflammatory focus
What are the effects of oxygen free radicals and what are their names?
H2O2, OH-, O2-
Released by neutrophils on phagocytosis
Amplify other mediator effects
What are the different plasma enzymes involved?
Blood coagulation pathways - clotting fibrinogen in exudate
Fibrinolysis - breaks down fibrin maintaining blood supply. The breakdown products are vasoactive
Kinin system - bradykinin is responsible for pain
Complement cascade -
Increase permeability, chemotaxis, phagocytosis, cell breakdown
What is the pathogenesis of septic shock?
There is a release of chemical mediators from cells into plasma
Mediators cause vasodilation
Vasodilation results in loss of systemic vascular resistance
This results in catecholamine (adrenaline and noradrenaline release)
Tachycardia follows to maintain cardiac output
Bacterial endotoxins are released (interleukin- 1 - pyrexia)
The increased heart rate is insufficient to maintain cardiac output during septic shock, what is the effect of this?
Blood pressure drops due to reduced SVR
There is a reduced perfusion of tissues, hypoxia and loss of cell tissue and organ function
What is the outcome of septic shock?
Rapidly fatal
Tissue hypoxia
Haemorrhage
Requires immediate intervention and support
What are the outcomes of acute inflammation?
Resolution
Suppuration
Organisation
Dissemination
Chronic inflammation
