Acute Inflammation Flashcards
Acute Inflammation
respond/protective changes to maintain intergrity, localised in site of injury
Redness that doesnt cease
Rubor tumor dalor (pain) calor (heat) + loss of function
takes place in microcirculation
Flow (Q) is proportional to r (power of 4)
Poiseuille’s Law
Control flow (fluid flux) across membrane (hydrostatic and colloid osmotic pressures compartments and physical constants)
Starling forces
neutrophil move to endothelial aspect of lumen
Margination
neutrophil attach to endothelial walls
Pavementing
neutrophil squeeze between endothelial cells to ECF
Emigration
Rouleux formation
RBCs aggregration
Effects of exudation
oedema formation = swelling
Vasodilation and Increased Permeability
Increased blood - Increase HP inside - drives fluid pressure - leaks out
= Proteins and fluid leaking out of vessels
Decreased colloid pressure - conc inside lower
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
adhesion molecules appear on endothelial cells
ICAM-1 - help neutrophils stick
P-selectin - interacts with neutrophil surface
Cell surface mediators
Causes vasoconstriction
Preformed in platelets
Released when platelets degranulate in coagulation
5-hydroxytryptamine (serotonin)
Mediators Molecules released from cells
Increase conc of RBC as plasma protein pass between endothelial cells = Increase Viscosity = allows:
Stasis - blood pass slow - allows leucocyte - neutrophil - margination, pavementing, emigration
mobile phagocyte
chemotaxis
adherence
release granules = pus
Neutrophils
Form fibrin and clot exudate
fibrinogen (pp) - coag factor
Blood coag
clots fibrinogen in exudate
Pain
Bradykinin - Kinin System
Active components stimulate increased permeability, chemotaxis, phagocytosis, cell breakdown
Complement cascade (C3a )
preformed in mast cells beside vessels, platelets, basophils
released as a result of local injury; IgE mediated reactions
causes vasodilatation, increased permeability - H1 receptors on endothelial cells
Histamine (mediator)
thromboxane A2 promotes platelet aggregation and vasoconstriction – the opposite effect to PGD2, PGE2, etc
Prostaglandins
neutrophils especially
vasoactive - dynamic effect on vessels to increase permeability and constrict smooth muscle
leukotrienes
decrease synthesis of arachidonic acid derived inflammatory mediators
Omega-3 FA
cell memb - activated inflammatory cells
Reduce permeability by enhancing platelet granulation at site of injury
Platelet-activating factor (PAF)
Small molecules produced by macrophages, lymphocytes, endothelium in response to inflammatory stimuli
Attract inflammatory cells
cytokines and chemokines (eg TNFα, IL-1)
smooth muscle relaxation (vasodilation), anti-platelet, regulate leukocyte recruitment to inflammatory focus
NO
Released by neutrophils on phagocytosis
Amplify other mediator effects
Oxygen free radicals (H2O2, OH-, O2-)
Breaks down fibrin, helps maintain blood supply
Fibrin breakdown products - vasoactive
fibrinolysis
Pyrexia - fever
Unwell - malaise (discomfort), anorexia, nausea, abd pain, vomiting in children
T - temp increase - pyrogens - WBC - central
Immediate systemic effect of inflamm
Lymphadenopathy - regional lymph node enlargement
immune response
weight loss - catabolic process
anaemia
Longer term effect
Pus (soup)
Pyogenic membrane surrounds pus (capillaries sprout)
Outcome of inflammation - suppuration
Abscess - collection of pus under pressure “points” and discharges; collapses - healing and repair
Empyema - pus in a hollow viscus - gall bladder, pleural cavity
Pyaemia - discharge to bloodstream
Granulation tissue characteristic
Healing and repair
=collagen - Leads to fibrOsis and formation of a scar
Outcome of inflammation - Organisation
Granulation tissue -new capillaries - angiogenesis, fibroblasts and collagen, macrophages
these happen if resolution fail
new capillaries grow, macrophages and fibroblasts on the site of injury
Spread to bloodstream - patient “septic”
DiSsemination
bacteraemia - bacteria in blood
septicaemia - growth of bacteria in blood
toxaemia - toxic products in blood
Clinical Features of Septic Shock
inability to perfuse tissues tachycardia - high HR hypotension periperal vasodilatation often pyrexia
Outcome of septic shock rapidly fatal tissue hypoxia - cell death haemorrhage requires urgent intervention and support admit to hospital and intensive care
Pathogenesis of septic shock
loss of systemic vascular resistance (SVR)
results in catecholamine release
bacterial endotoxin released - IL-1 - acts on hypothalamus - pyrexia
activation of coagulation
vasoactive chemical - vasodilatation
haemorrhagic skin rash
tachycardia (increased heart rate) follows to maintain cardiac output because (CO=SV x HR)
Ideal outcome of Acute inflamm
resolution
