Acute Inflammation Flashcards
Define acute inflammation
A fundamental response to maintain the integrity of organism
A series of protective changes occurring in living tissue as a response to injury
What are the cardinal signs of inflammation
Rubor - redness Calor - heat Tumor - swelling Dolor - pain Loss of function
What are the causes of acute inflammation
Microorgansims -including bacteria, fungi, viruses, parasites
Mechanical trauma - injury to tissues even in surgery
Chemical - unstable environment e.g. upset pH or bile and urine causing irritation when in inappropriate places
Physical - extreme conditions e.g. heat, cold, ionising radiation
Dead tissue - cell necrosis irritates adjacent tissue
Hypersensitivity - causes several classes of reaction
What changes occur in acute inflammation
Changes in:
Vessel radius (flow)
The permeability of the vessel wall (exudation)
And movement of neutrophils from the vessel to the extravascular space
What are the benefits of acute inflammation
A rapid response to non-specific insult
Cardinal signs and loss of function (allowing transient protection of the inflamed area)
The neutrophils destroy organisms and denature antigens for macrophages
Plasma proteins localise the process
It can be resolved and return to normal
What is acute inflammation
Series of microscopic events occur which are localised to the affected tissue
They take place in the microcirculation
Result in the clinical symptoms and signs of acute inflammation
What happens in the process of exudation
There is a net movement of plasma from capillaries to extravascular space causing fluid to be leaked which is exudate
Exudate fluid is rich in protein and plasma and it includes Ig and fibrinogen
What can exudation cause
Oedema - the accumulation of fluid in the extravascular space
Presents as the swelling of tissue in acute inflammation which cause pain and reduce function
How are inflammation at various anatomical positions named
“Structure”-itis
e.g. peritoneal cavity inflammation is peritonitis, meninges inflammation is meningitis, appendix inflammation is appendicitis.
What is an exemption to the rule of how inflammation is named
Lungs which is known as pneumonia
Pleural cavity is known as pleurisy
What is the role of neutrophils
They are mobile phagocytes Recognise foreign antigen Adhere to organism Release granule contents Phagocytose and destroy foreign antigen
What do the granules in neutrophils contain
Oxidants (e.g. H202)
Enzymes
What happens to the neutrophil when the granule contents are released
They die
What is produced from a neutrophil
A ‘soup’ of fluid
Bits of cell
Organisms
Endogenous proteins
This is known as pus
What is fibrinogen
A coagulation factor which forms fibrin and colts exutade
It localises inflammatroy processes
What is the role of immunoglobulins in plasma
They are specific for the antigen
Involved in the humoural immune response
Name the type of mediators in acute inflammation
Molecules on endothelial cell surface membrane,
Molecules released from cells
Molecules in the plasma
What are the collective effects of mediators
Vasodilatation Increased permeability Neutrophil adhesion Chemotaxis Itch and pain
What are cell surface mediatiors
Adhesion molecules which appear on endothelial cells
Give example of cell surface mediatiors
ICAM-1 which help neutrophils stick
P-selectin which interact with the neutrophil surface
Give examples of the molecules released from cells
Histamine
5-hydroxytryptamine (serotonin)
Prostgladins (arachidonic acid metabolites via cyclo-oxygenase pathway)
Leukotrienes (arachidonic acid metabolites via lipoxygenase pathway
Omega-3 polyunsaturated fatty acids
Platelet-activating factor (PAF)
Cytokines and chemokines (e.g. TNFα, IL-1)
Nitric oxide (NO)
Oxygen free radicals (H2O2, OH-, O2-)
Describe histamine
Preformed in mast cells beside vessels, platelets and basophils
Released due to local injury which cause IgE mediated reactions
Cause vasodilatation
Increase permeability
Act via H1 receptors on endothelial cells
Describe 5-hydroxytryptamine (serotine)
Preformed in platelets
Released when platelets degranulate in coagulation causing vasoconstriction
Describe prostglandins (arachidonic acid metabolites via cyclo-oxygenase pathway)
Formed from many cells including endothelium and leukocytes
Many of the cells promote histamine effects and inhibit inflammatory cells
Give an example of a prostglandins and its actions
Thromboxane A2
Promotes platelet aggregation and vasoconstriction
Opposite to PGD2 and PGE2
PGE determines the effectiveness of non-steroidal anti-inflammatory drugs.
Give examples of leukotrines
Neutrophils
They are vasoactive so have a dynamic effect on vessels to increase permeability as well as constrict smooth muscle
What are prostglandins
Arachidonic acid metabolites from the cyclo-oxygenase pathway
What are leukotrines
Arachidonic acid metabolites from the lipoxygenase pathway
What do omega-3 polyunsaturated fatty acids do
Decrease the synthesis of arachidonic acid that is derived from inflammatory mediators
Where are platelet-activating factors (PAF) present
Cell membrane of activated inflammatory cells
What is the function of platelet-activating factors (PAF)
Reduce the permeability of cell membranes through the enhancement of platelet degranulation at the site of injury
What are cytokines and chemokines
Small molecules produced by macrophages, lymphocytes and endothelium in response to inflammatory stimuli
What do cytokines and chemokines do
Attract inflammatory cells
Where is nitric oxide (NO) found
In various cells
What does nitric oixide do
Promotes smooth muscle relaxation and anti-platelets
Regulates recruitment to the inflammatory focus
Where are oxygen free radicals released from
Neutrophils in phagocytosis
What do oxygen free radicals do
Amplify other mediator effects
Give examples of oxygen free radicals
H2O2
OH-
O2-
Name 4 plasma mediators
Blood coagulation pathways
Fibrinolysis
Kinin system
Complement cascade
What does the blood coagulation pathway do
Clots fibrinogen in exudate
Interacts widely with other systems
What does fibrinolysis do
Breaks down fibrin to help maintain blood supply
Fibrin breakdown products are vasoactive.
What does the kinin system do
Produces bradykinin to cause pain (reduce pain threshold)
What does the complement cascade do
Ties inflammation with the immune system
The active components stimulate increased permeability, chemotaxis, phagocytosis and cell breakdown.
What are the overall effects mediators can cause
Vasodilatation and constriction Altered permeability Neutrophil adhesion Chemotaxis Itch and pain
Mediators…
Have positive and negative effects, result is a dynamic balance, favours and inhibits acute inflammation, relative to need
List the systemic effects of acute inflammation
Pyrexia (raised temperature) - the endogenous pyrogens from white cells will act centrally
Feeling unwell – this can include: malaise, anorexia and nausea (abdominal pain and vomiting in children)
Neutrophilia (raised white cell count) - bone marrow releases/produces more
Lymphadenopathy (regional lymph node enlargement) – this is due to an immune response
Weight loss – catabolic process
Anaemia
Shock – inability to perfuse tissues
What is suppuration
Pus formation
What does pus contain
Dead tissue Organisms Exudate Neutrophils Fibrin Red cells Debris
What does the pyogenic membrane surround
Pus (walls off pus)
What does the pyogenic membrane contain
Capillary sprouts
Neutrophils
Fibroblasts
What is an abscess
A collection of pus under pressure which can either be a single locule or multiloculated
What do abscess have
‘Points’ and discharges
How does a multiloculated abscess occur
When pus bursts through the pyogenic membrane and forms new cavities
What is an empyema
A hollow viscus of pus either in the gall bladder or pleural cavity
What is a pyaemia
When discharge (pus) enters the bloodstream
What is organisation (an outcome of inflammation)
Granulation tissue
Healing and repair
Leads to fibrosis and formation of a scar
What is granulation tissue
A ‘universal patch’ i.e. a repair kit for all damage
What is granulation tissue formed of
New capillaries (angiogenesis)
Fibroblasts and collagen
Macrophages
What is dissemination
An outcome of acute of inflammation where there is a spread into the bloodstream
What is bacteraemia
Bacteria in the blood
What is septicaemia
Growth of bacteria
What is toxaemia
Toxic products in the blood
What are the components of cardiovascular physiology
Blood pressure (BP) Cardiac output (CO) Stroke volume (SV) Heart rate (HR) Systemic vascular resistance (SVR)
How can cardiac output be calculate
CO = SV x HR
How can blood pressure be calculated
BP = CO x SVR
State the indications of early septic shock
Peripheral vasodilatation Tachycardia - high heart rate Hypotension - low blood pressure Often pyrexia Sometimes haemorrhagic skin rash
How does septic shock occur
Through the systemic release of chemical mediators from cells into plasma
What do the mediators released in septic shock cause
Vasodilation causing loss of systemic vascular resistance (SVR)
Results in catecholamine release
Tachycardia follows to maintain cardiac output because the increased heart rate compensates
What type of bacterial toxin is released in septic shock
Interleukin-1 which acts on hypothalamus causing pyrexia
What does the activation of coagulation in septic shock cause
Disseminated intravascular coagulation Vasoactive chemicals (vasodilatation) Haemorrhagic skin rash
What happens when the increased heart rate compensation fails
The raised HR is insufficient to maintain the cardiac output so SVR is low and BP falls.
This means there is reduced perfusion of the tissues causing tissue hypoxia and the loss of cell tissue and organ functions
What is the outcome of septic shock
It is rapidly fatal
Tissue hypoxia - cell death
Haemorrhage
What does septic shock require
Urgent intervention and support
