acute inflammation Flashcards
Why does redness occur in acute inflammation?
Vessels are dilated
Why does osmotic pressure in capillaries decrease during acute inflammation?
Increased hydrostatic pressure means more fluid and proteins forced out and venular permeability is increased and gradient for reabsorption is reduced
Where is histamine produced in
Mast cells
Basophils
Platelets
What type of genetic condition is hereditory angioedema
Autosomal dominant
what type of genetic condition is alpha antitrypsin deficiency
Autosomal recessive
What stimulates increased selectin expression by endothelial cells in neutrophil extravasation
IL-1
TNF
What stimulates diapedesis (extravasation)?
C3a
Leukotriene B4
Bacterial peptides
What opsonins does neutrophils coat pathogens in
C3b and IgG
What occurs to arterioles in vascular phase of acute inflammation
Transient vasoconstriction and vasodilatation
What occurs in vascular phase of acute inflammation
Changes in blood flow - increased
Movement of fluid into tissue
What occurs in the cellular phase of acute inflammation
Infiltration of inflammatory cells
What occurs in suppuration
formation of pus
becomes walled off and abscess forms
What occurs in resolution of acute inflammation
mediators have short half lives and degrade
exudate drains into lymphatics
fibrin broken down by thrombolytic process
What occurs in oxygen-dependant killing mechanisms with neutrophils
Oxygen free radicals released into phagosome
Hypochlorite produced
What occurs in chronic granulomatous disease
neutrophil unable to generate free radicals superoxide hence cannot kill bacteria
What mediates structural re-organisation of cytoskeleton in vascular leakage
IL-1
TNF
What mediates endothelial cell contraction in vascular leakage
Histamines
C5a
NO(nitric oxide)
What is VEGF(Vascular endothelial growth factor)
Signalling protein that promotes growth of new vessels
What is vascular stasis
Blood becoming more viscous due to increased concentration of red cells in vessels
What is transudate fluid
low protein content fluid
What is transcytosis
molecules captured in vesicles at one side and ejected at other side
What is the role of exudation of fluid in acute inflammation
Dilute toxins and reduce impact
deliver plasma proteins, IGs and mediators to injure site
What is the role of chemical meditators
Modulate inflammatory response
process for neutrophil extravasation
Neutrophil line up along endothelium (margination)
Roll along endothelium (rolling)
Stick to endothelium (adhesion)
Emigrate through endothelium (diapedesis)
process for neutrophil extravasation
Neutrophil line up along endothelium (margination)
Roll along endothelium (rolling)
Stick to endothelium (adhesion)
Emigrate through endothelium (diapedesis)
What is the oxygen independant killing mechanism of neutrophils
Enzymes such as lysozymes and proteases from neutrophil granules form holes in microbes
What is the deficiency in hereditory angioedema
C1 esterase inhibitor
What is the complement system activated by(4)
proteolytic enzymes from necrotic cells
antigen-antibody complexes
gram negative bacteria
products of kinin and fibrinolytic systems
What is the apperance of purulent exudate
thick, opaque drainage that is tan, yellow, green, or brown
What is starling’s law in relation to capillaries
Movement of fluid across vessel wall due to balance between hydrostatic and osmotic pressure between intravascular and extravascular space
What is serous exudate
clear, thin, watery plasma drainage
What is sequence after acute inflammation
resolution of inflammation
Suppuration (excess exudate formation)
chronic inflammation
death
What is purulent exudate
inflammatory exudate with a high concentration of leukocytes - predominantly neutrophils
What is indirect endothelial cell injury
Damage to endothelial cell as a side effect of another action
Reactive oxygen species production
Proteolytic enzymes released from neutrophils
What is haemorrhagic exudate
drainage of a thin, watery, pink coloured fluid composed of blood and serum.
What is fibrinous exudate
exudate containing large amount of fibrinogen and fibrin
What is exudate fluid
high protein content fluid
What is expressed by neutrophils during adhesion phase of neutrophil extravastion
integrins
What is expressed by endothelial cells during the rolling phase of neutrophil extravasation
Selectins
What is direct endothelial cell injury
Injury due to trauma,chemicals of toxins released from microbes
What is chemotaxis
movement along concentration gradients
What is bradykinin produced from
Plasma precursor kininogen
What is an example of a vasoactive peptide
bradykinin
What is alpha antitrypsin
Protease inhibitor which deactivates enzymes released from neutrophils during inflammation
What is acute inflammation
Protective rapid response of living tissue to injury
What increases expression of integrin production by neutrophils
C5a
LTB4
IL-1
TNF
What does oedema elicit in acute inflammation
Increased lymphatic drainage
deliver antigen to immune system
What does exudation of fluid deliver to area of injury
Plasma proteins
immunoglobulins
inflammatory mediators
What do selectins expressed by endothelial cells in neutrophil extravasation bind to
Carbohydrate ligands on neutrophils
What do pyrogenic cytokines act on
Anterior hypothalamus
what do integrin expressed by neutrophils during adhesion phase of neutrophil extravasation bind to
integrin ligands on endothelium
What cytokines accelerate release of leucocytes from bone marrow
IL-1
TNFa
What cell is serotonin produced from
Platelets
What can trigger pyrexia in acute inflammation
Bacterial endotoxins
pyrogenic cytokines
What can cause acute inflammation(4)
Microbial infections
physical and chemical agents
tissue necrosis
hypersensitivity reactions
What are the types of exudate(4)
Purulent
Haemorrhagic
serous
fibrinous
What are the mechanisms of vascular leakage in vascular phase of acute inflammation
Endothelial cell contraction
Endothelial cell injury
structural re-organisation of cytoskeleton
Transcytosis
What are the hallmarks of acute inflammation
Exudate of fluid
Infiltrate of cells
What are the clinical signs of acute inflammation
Redness - rubor
swelling - tumor
heat - calor
pain - dolor
loss of function
What are the 4 main systemic effects of acute inflammation
pyrexia
leucocytosis
acute phase response in liver
Shock
What are the 3 enzymatic cascade systems used to produce endogenous inflammatory mediators
Coagulation system
Kinin system
Complement system
What are the 2 types of endothelial cell injury
Direct
indirect
What are the 2 phases in acute inflammation
Vascular and cellular phase
What are the 2 different killing mechanisms of neutrophils
Oxygen dependent and oxygen-indepedent
What are the 2 categories of extravascular fluid
Transudate
Exudate
What are some features of acute inflammation
Immediate
short duration
innate immune system involved
What are some examples of vasoactive amines
Histamine
Serotonin
What are some examples of pyrogenic cytokines
IL-2
TNF
What are some examples of local complications that can occur in acute inflammtion
Swelling
Inappropriate inflammation
Exudation of fluid
Loss of fluid
Prolonged pain and loss of function
Digestion of host tissue by enzymes released by neutrophils
What are some clinical features of acute inflammation(3)
Involves vascular and cellular reactions
controlled by chemical mediators that are inactive
It is a protective mechanism that can lead to complications
What are some acute phase proteins produced during acute phase response in liver
Fibrinogen
CRP (C-reactive protein)
Alpha 1 antitrypsin
What are prostaglandins produced from
Phospholipids by cyclo-oxygenase
What are MMP’s
Matrix metallopeptidases
degrade both matrix and non-matrix proteins
What are leukotrienes
family of eicosanoid inflammatory mediators produced by leukocytes
What are leukotrienes
family of eicosanoid inflammatory mediators produced by leukocytes
What are features of chemical mediators
Short lived
Can be endogenous or exogenous
has an inhibitor
What are examples of endogenous chemical mediators
Vasoactive amines
Vasoactive peptides
Chemokines
Arachidonic acid metabolites
Nitric oxide
What are examples of arachidonic acid metabolites
Prostaglandins
Leukotrienes
How is hydrostatic pressure increased in capillaries in acute inflammation
Arteriolar dilation
How does vasodilation combat injury in acute inflammation
Increases delivery and temperature
How does pain and loss of function combat injury in acute inflammation
Enforces rest and reduce chance of further injury
How does infiltration of inflammatory cells combat injury
Remove pathogenic organisms and necrotic debris
How does body stimulate leucocytosis
macrophages and endothelial cells release colony stimulating factors so bone marrow produces more leucocytes
How does blood flow change in vascular phase of acute inflammation
Transient vasoconstriction of arterioles
Vasodilation of arterioles to increase blood flow
Increased vascular permeability
Vascular stasis
How do pyrogenic cytokines cause pyrexia
Increase synthesis of prostaglandin E2
How do neutrophils escape from vessels
Intracellular junctions relax
Collagenase released and breaks down capillary basement membrane
MT-MMP and MMP produced
what does the complement cascade generate?
C3 - functions as opsonin
c5a - attracts neutrophils
c5-9 complex - attach to cell cause lysis
examples of anti-inflammatories
aspirin/NSAIDs
antihistamines
TNF alpha antagonists - infliximab
corticosteroids
