acute inflammation Flashcards
Define acute inflammation
Fundamental response maintaining integrity of organism
- dynamic homeostatic mechanism
- higher organisms
Series of protective changes occurring in living tissue as a response to injury
Cardinal signs of inflammation
Rubor - redness Calor - heat Tumor - swelling Dolor - pain Loss of function
Aetiology of inflammation
Micro organisms - pathogenic organisms cause infection
Mechanical - Trauma - Injury to tissue
- all injuries even sterile eg surgery
Chemical - upset stable environment
- acid or alkali - upset pH
- bile and urine - irritation when in inappropriate place eg peritoneum
Physical - extreme conditions
- heat - sunburn
- cold - frostbite
- ionising radiation
Dead tissue - cell necrosis irritates adjacent tissue
Hypersensitivity
- several classes
Processes of acute inflammation
Series of microscopic events
Localised to affected tissue
Take place in microcirculation
Result in clinical symptoms and signs of acute inflammation - cardinal signs
What is microcirculation?
Capillary beds, fed by arterioles and drained by venules
Extracellular space and fluid and molecules within it
Lymphatic channels and drainage
Starling forces control flow across membrane
Dynamic balance - hydrostatic and colloid osmotic pressures
Compartments and physical constants
Pathogenesis
Changes in vessel radius
Change in permeability of the vessel wall - exudation
Movement of neutrophils from the vessel to the extravascular space
Local changes in vessel radius and blood flow
Transient arteriolar constriction - few moments, probably protective
Local arteriolar dilatation - active hyperaemia
Relaxation of vessek smooth muscle - autonomic NS or mediator derived
“Triple response” - flush, flare, wheal
What is an exudate?
fluid rich in protein - plasma - includes immunoglobulin and fibrinogen
Effects of exudation
oedema
What is oedema?
accumulation of fluid in the extravascular space
swelling - causes pain, reduces function
Explain flow in inflammation
neutrophil polymorphonuclear leukocyte is most important cell
loss of laminar flow
red cells aggregate in centre of lumen - rouleaux formation
neutrophils found near endothelium - margination
Phases of emigration of neutrophils
margination - neutrophils move to endothelial aspect of lumen
pavementing - neutrophils adhere to endothelium
emigration - neutrophils squeeze between endothelial cells - active process - to extravascular tissues
What is diapedesis?
passage of blood cells through intact walls of capillaries typically accompanying inflammation
Resolution of acute inflammation - ideal outcome
inciting agent isolated & destroyed macrophages move in from blood and phagocytose debris; then leave epithelial surfaces regenerate inflammatory exudate filters away vascular changes return to normal inflammation resolves
Benefits of acute inflammation
rapid response to non-specific insult
cardinal signs and loss of function - transient protection of inflamed area
neutrophils destroy organisms and denature antigen for macrophages
plasma proteins localise process
resolution and return to normal
Outcomes of acute inflammation
resolution suppuration organisation dissemination chronic inflammation
examples of conditions
appendicitis pleural inflammation bacterial endocarditis acute pyelonephritis gingivitis
Neutrophils - function
They are mobile phagocytes which recognise foreign antigens and move towards them, this is called chemotaxis. Then adhere to organisms.
granules possess oxidants (egH2O2) and enzymes (eg proteases)
release granule contents
phagocytose and destroy foreign antigen
Consequences of neutrophil action
neutrophils die when granule contents released
produce a “soup” of fluid, bits of cell, organisms, endogenous proteins - pus
might extend into other tissues, progressing the inflammation
What is the role of plasma proteins in inflammation?
fibrinogen - coagulation factor - forms fibrin and clots exudate - localises inflammatory process
immunoglobulins in plasma specific antigen - humoral immune response
Mediators of acute inflammation
molecules on endothelial cell surface membrane
molecules released from cells
molecules in the plasma
molecules inside cells
What are the collective effects of mediators?
vasodilation increased permeability neutrophil adhesion chemotaxis itch and pain
What are cell surface mediators?
adhesion molecules appear on endothelial cells
eg ICAM-1 help neutrophils stick
P-selectin interacts with neutrophil surface
Give examples of molecules released from cells
histamine
- preformed in mast cells beside vessels, platelets, basophils
- released as a result of local injury; IgE mediated reactions
- causes vasodilation, increased permeability
- acts via H1 receptors on endothelial cells
5-hydroxytryptamine (serotonin)
- preformed in platelets
- released when platelets degranulate in coagulation
- vasoconstriction
other common molecules released from cells
prostaglandins
cytokines and chemokines
nitric oxide
oxygen free radicals
What are intracellular inflammation pathways?
NF-kB - nuclear factor kappa-B pathway
MAPK - mitogen-activated protein kinase
- stimulated in inflammation via surface receptors eg toll-like receptors
- regulates pro-inflammatory cytokine production and inflammatory cell recruitment
JAK-STAT - Janus kinase - signal transducer and activator to transcription pathway
- direct translation of extracellular signal to molecular expression
Plasma - interaction of 4 enzyme cascades
blood coagulation pathways
fibrinolysis
kinin system
complement cascade
Blood coagulation pathways
clots fibrinogen in exudate
interacts widely with other systems
Fibrinolysis
breaks down fibrin, helps maintain blood supply
fibrin breakdown products vasoactive
Kinin system
bradykinin: pain
Complement cascade
ties inflammation with immune system
active components stimulate increased permeability, chemotaxis, phagocytosis, cell breakdown
immediate systemic effects of inflammation
pyrexia
feel unwell - malaise, anorexia, nausea, abdominal pain and vomiting in children
neutrophilia - raised white blood cell count - bone marrow releases/produces
Longer term effects of acute inflammation
lymphadenopathy - regional lymph node enlargement - immune response
weight loss - catabolic process
anaemia
Suppuration - outcome of inflammation
pus formation - dead tissue, organisms, exudate, neutrophils, fibrin, RBCs, debris
pyogenic membrane surrounds pus - capillary sprouts, neutrophils, fibroblasts
- walls of pus
What is an abscess?
collection of pus (suppuration) under pressure
single locule, multiloculated
“points” and discharges
collapses - healing and repair
organisation outcome
granulation tissue characteristic
healing and repair
leads to fibrosis and formation of a scar
What is granulation tissue?
“universal patch” - repair kit - for all damage
formed of
- new capillaries - angiogenesis
- fibroblasts and collagen
- macrophages
Dissemination outcome
spread to bloodstream - patient “septic”
bacteraemia - bacteria in blood
septicaemia - growth of bacteria in blood
toxaemia - toxic products in blood
Pathogenesis of septic shock
systemic release of chemical mediators from cells into plasma
- mediators cause vasodilation causing loss of systemic vascular resistance
- results in catecholamine release
- tachycardia (increased HR) follows to maintain CO because 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 - vasodilatation
- haemorrhagic skin rash
When HR is insufficient to maintain CO
SVR low; therefore BP falls
- BP = CO x SVR
- increasing HR insufficient (CO = SV x HR)
reduced perfusion of tissues
- tissue hypoxia
- loss of cell tissue and organ function
