Acute inflammation Flashcards
acute inflammation overview
- immediate response
- short duration
- innate
- stereotype
- limits damage
stereotyped meaning
always the same regardless of the stimulus
acute inflammation is tightly controlled by
chemical emdiators
although acute inflamamrtionc an be protective
can give rise to complications
phases of acute inflammation (2)
1) vascular phase
2) cellular phase
1) vascular phase
- changes in blood flow
goal of vascular phase
accumulation of exudate
2)cellular phase
delivery of neutrophils
what causes inflammation
- Trauma/foreign body
- Microorganisms
- Hypersensitivity (pollen and gluten)
- Other illnesses e.g. necrosis
clinical signs of acute inflammation
- Tumor- swelling
- Rubor- redness
- Calor- heat
- Dolor- pain
- Loss of function
outline the vascular phase
- stimulus causes vasoconstriction (only lasts a few seconds)
- Then vasodilation (minutes)
- heat and redness
- allows more blood to flow to area - vessel becomes more permeable allowing fluid, cells and proteins to escape
vasoconstriction
increase capillary hydrostatic pressure
increased vessel permeability
Plasma proteins move into interstitial space. Increased interstitial oncotic pressure
fluid movement
Out of vessel into interstium – OEDEMA (swelling/tumor)
fluid movement out of vessel
Out of vessel into interitem – OEDEMA (swelling/tumor)
- Increases viscosity of blood
- Reducing flow through the vessel- STATSIS
starlings law
Movement of fluid controlled by the balance of hydrostatic pressure and oncotic pressure
hydrostatic pressure
ressure exerted on vessel wall by fluid- pushes water out of vessels
oncotic pressure
the pressure exerted by proteins- draws fluid back into vessel (proteins)
types of interstitial fluid
exudate and trannsudatre
exudate
- Arises due to change in vascular permeability
- Protein rich interstitial fluid
- Occurs due to inflammation
transudate
not released during inflammation
- Vessel permeability unchanged
- Not due to change in protein conc in the interstitial
- Fluid movement due to
- Increased capillary hydrostatic pressure
- Reduced capillary oncotic pressure
o E.g. heart failure/hepatic failure (reduced production of proteins) /renal failure (lose protein in the urine)
o Can cause pulmonary oedema- fluid escapes in blood
how do the vessels become leaky?
1) Endothelial cells retract meaning space between them is bigger- passive of cells, fluid etc
- Due to chemokines e.g. histamine
2) Endothelial cell damage allow proteins and cells to escape
3) Leukocytes (WBC e.g. neutrophils) become activate which release enzymes which damage the endothelial cells
why is vascular phase important
• Interstitial fluid dilutes toxins
• Exudates- delivers proteins
- e.g. fibrin -mesh limits spread of toxins around the body
- e.g. immunoglobulins from adaptive immune response
• Fluid drains to lymph nodes - delivery of antigens —> stimulates immune response (proliferation of lymphocytes)
cellular phase (2) is centred around the
neutrophil
neutrophil
- Primary white blood cell involved in acute inflammation
- Trilobed nucleus
- A granulocytes
- Bigger than RBC
how do neutrophils escape the vessel
1) Neutrophil margination- helped by thickness of blood
2) Rolling- weak intermittent bonds form between neutrophil and endothelium
• Selectins- expressed on activated endothelial cells (activated by chemical mediators)
o Responsible for rolling
• Integrins- found on neutrophil surface
o Change from low affinity to high affinity state – responsible for adhesion
3) Adhesion
4) Emigration (diapedesis)
selecting
responsible for rolling
integrins
found on neutrophil surface- responsible for adhesion
diapedesis
the passage of blood cells through the intact walls of the capillaries, typically accompanying inflammation.
selectins
expressed on activated endothelial cells (activated by chemical mediators)
o Responsible for rolling
chemotaxis
Movement along an increasing chemical gradient of chemoattractant
chemoattractants
o Bacterial peptides, inflammatory mediators (CF5a, LTB4)
o Rearrangement of neutrophil cytoskeleton
role of neutrophils
1) Phagocytosis
2) release inflammatory mediators
phagocytosis
o Bacterial peptides, inflammatory mediators (CF5a, LTB4)
o Rearrangement of neutrophil cytoskeleton
how do neutrophils recognise targets for phagocytosis
- Opsonisation
outline opsonisation
o Pathogen becomes coated in molecules such as complement (C3b and Fc)
o Neutrophil has corresponding receptors- receptor binds to ligand and neutrophil introduced to pathogen
how do neutrophils kill (2)
1) Oxygen dependent
2) Oxygen independent
1) Oxygen dependent
o Reactive oxygen intermediates (Free radicals e.g. ROS and RNI)
O. (superoxide anion)
OH. (hydroxyl radicals)
H2O2 (hydrogen peroxide)
2) oxygen independent
Enzymatic
Lysozyme
Hydrolytic enzymes e.g. defensins
how is the cellular phase effective
1) Removal
• Pathogens
• Necrotic tissue
2) Release
• Inflammatory mediators
chemical mediators
- Control and co-ordinate the inflammatory response
- Varying chemical structures
- Overlapping functions
chemical mediators originate from
- Activated inflammatory cells
- Platelets
- Endothelial cells
- Toxins themselves
chemical mediators which cause vasodilation
o Histamine
o Serotonin
o Prostaglandins
o Nitric oxide
chemical mediators which cause leaky vessels
o Histamine
o Bradykinin
o Leukotrienes
o C3a and C5a
chemical mediators which cause chemoattraction
o C5a
o TNF-a
o IL-a
o Bacterial peptides
chemical mediators which cause increased body temp
o Prostaglandins
o Il-1
o Il-6
o TNF-a
chemical mediators which cause pain
o Bradykinin
o Substance P
o Prostaglandins
complications of acute inflammation can be
local or systemic
local complications
- swelling
- exudate
- loss of fluid
- pain
Swelling
o Compression of tubes e.g. airway (epiglottitis)/bile duct/intestines
exudate
compression of organs e.g. cardiac tamponase
loss of fluid
e.g. burns (die of severe dehydration)
pain
muscle atrophy, psycho-social consequences etc
systemic complications
- fever
- leucocytosis
- acute phase repsonse
- septic shock
fever
o Brought about by chemical mediators – pyrogens
E.g. prostaglandins, IL-1,IL-6 etc
Act on hypothalamus to alter temperature
• Use NSAIDs
o Block COX enzymes (involved in production of prostaglandins)
leucoytosis
o Leucoytosis
Increased production of white cells
Inflammatory mediators act on bone marrow promoting production of WBC in bone marrow
• WBC conc can be measured in blood
Bacterial
- neutrophils
Viral
- lymphocytes
acute phase response
Brought about by acute phase proteins e.g. CRP • Common blood test-marker of severity • Useful in monitoring inflammation and infection (would expect CRP to come down with antibiotics) • Causes: o Malaise o Reduced appetite altered sleep o Tachycardia All induce rest
septic shocj
Huge release of chemical mediators • Widespread vasodilation • Hypotensions, tachycardia o Cant pump blood to the heart • Multi-organ failure • Can be fatal
what happens after acute inflammation
(1) Complete resolution
o Mediators have short half lives – diluted, inactivated/ derailed
o Vessel calibre and permeability returns to normal
o Neutrophil undergoes apoptosis and get phagocytised
o Exudate drained
(2) Repair with connective tissue (fibrosis)- if there has been substantial destruction
(3) Progression to chronic inflammations
o Prolonged inflammation with repair
appendicitis
o Blocked lumen (fecalith- hard faeces)
o Accumulation of bacteria and exudate
Increased pressure and perforation
pneumonia
o Many causative organisms Streptococcus pneumoniae Haemophilus influenzae o Signs and symptoms: Shortness of breath Cough Sputum Fever o Risk factor: Pre-existing lung condition (COPD, asthma/ malignancy)
bacterial meningitis
o Brain covered by meninges Becomes infected E.g. Group B streptococcus E.coli Neisseria meningitides o Signs and symptoms Headache Neck stiffness- meninges also cover spinal cord Photophobia Altered mental state Need immediate antibiotics
abscess
accumulation of dead and dying neutrophils
o Associated with liquefactive necrosis
inflammation of serous cavities
o Exudate pours into serous cavities (variety of causes)
Pleural space= pleural effusion
Peritoneal space= ascites
Pericardial space= pericardial effusion
rare inflammatory disorders
- Hereditary angio-oedema
- Alpha-1 antityrpisn deficiency
- Chronic granulomatous disease
