Acute Inflammation Flashcards
What are the 3 main responses involved in acute inflammation?
– Vascular dilation
– Increased vascular permeability
– Neutrophil activation and migration
What are the main causes of inflammation?
- Microbial infection
– Resulting from microbial recognition - Physical agents
– Physical trauma
– Ultraviolet or other radiation
– Heat (burns)
– Cold (frostbite) - Irritant and corrosive chemicals
– Acids, alkali, oxidizing agents
– Microbial virulence factors - Tissue necrosis
– Lack of oxygen or nutrients
– Inadequate blood flow (infarction)
What are the 5 cardinal signs of inflammation?
- Redness (rubor)
– Dilation of small blood vessels - Heat (calor)
– Increased blood flow (hyperaemia) - Swelling (tumor)
– Accumulation of fluid in extra vascular space (oedema) - Pain (dolor)
– Stretching/distortion of tissues due to oedema. – Chemical mediators induce pain - Loss of function
What disease is an example of acute inflammation?
gingivitis
What happens if there is no resolution to gingivitis?
periodontitis
During amplification, what occurs?
recruitment and activation of innate immune cells via chemokine/cytokine activity and vascular dilation
What is exudation?
the vessels become ‘leaky’ and allow passage of water, salts and some proteins
What are the vascular responses in inflammation?
- Small blood vessels adjacent to site of damage become dilated
- Endothelial cells swell and retract
- Exudation – the vessels become ‘leaky’ and allow passage of water, salts and some proteins
- Endothelial cells activated to promote immune cells passage to damaged tissues
What does exudation provide to tissues?
– Fluids and salts
– Glucose and oxygen
– Complement proteins and antibodies
– Fibrin (long insoluble filamentous protein)
What condition occurs during inflammation and what is it?
oedema
* Defined as an excess of watery fluid collecting in the cavities or tissues of the body.
* Increased blood and lymph flow
What are the chemical mediators of inflammation?
– Histamine
– Bradykinin
– Leukotrienes
– Serotonin
– Prostaglandins
What are the protein mediators of inflammation?
– Cytokines
– Chemokines
What is histamine, how is it stored/released and what is its role?
- Product of breakdown of amino acid histidine
- Stored in granules of immune cells such as mast cells
- Degranulation releases histamine
- Role as a neurotransmitter–itching
- Causes vascular dilation
- Many immune cells express histamine receptors
What are prostaglandins, how are they produced and what is their main role?
- Produced by macrophages and neutrophils (with leukotrienes)
- Product of fatty acid metabolism
- Most abundant is Prostaglandin E2 (PGE2)
- Causes vascular dilation
What are the other roles of prostaglandins in acute inflammation?
– Regulate cytokine production
– Regulate cell recruitment
– Act on nerve fibres – pain
– Involved in tissue remodelling
What enzyme regulates prostaglandins?
Cyclo-oxygenaseII (COXII)
What are the 4 enzymatic cascades of plasma?
– Complement
– The kinin system
– Coagulation
– Fibrinolytic system
What are the 3 pathways of complement?
(1) Classical pathway – antibody attached to microbe
(2) Alternative pathway – microbial cell wall
(3) Mannose binding lectin pathway (MBL) – carbohydrates on pathogen surface
Describe the kinin system
Involves a number of plasma proteins/enzymes
Hageman factor (coagulation factor XIIa) generates kallikrein
Kallikrein converts kininogens to kinins (e.g., bradykinin)
What are the 3 pathways of coagulation?
- Intrinsic (FXII) – activated when blood comes into contact with sub-endothelial connective tissues (outside blood vessel)
- Extrinsic – Damaged blood vessel means Human Factor VII (FVII) leaves vessel and encounters tissue factor in surrounding tissue
- Common – Production of thrombin which in turn produces fibrin from fibrinogen (clot formation)
Describe the fibrinolytic system
- Results in activation of plasmin from plasminogen via many activators (tPA, kallikrein, hageman factor)
- Activates complement (plasmin cleaves C3 – protein part of complement cascade)
- Indirect role as fibrin degradation products promote vascular permeability
What factor is involved in all plasma systems?
12 - Hageman Factor
What is haemostasis?
balance between the coagulation and fibrinolytic system
What are examples of congenital coagulation disorders?
– Von Willebrand disease (VWD)
– Haemophilia A
– Haemophilia B
What drugs are examples of acquired anti- coagulation?
– Warfarin
– Heparin
What is another outcome of acute inflammation?
Abscess formation (suppuration)
What is suppuration dependant on?
- Tissue involved
- Amount of tissue destruction
- Nature of the harmful agent
What are the 3 types of dental abscess?
- Gingival abscess
- Periodontal abscess
- Periapical abscess
What is suppuration?
the formation of pus usually arising from an infection.
What is pus?
bacteria with dead and dying neutrophils
What surrounds pus when it accumulates?
pyogenic membrane
What is an important part of suppuration?
neutrophil infiltration
What does complete restoration of tissues after an episode of acute inflammation require?
– Minimal cell death and tissue damage
– Occurrence in tissues with regenerative capacity
– Rapid elimination of causative agent
– Rapid removal of fluid and debris by
vascular/lymphatic drainage
Where do non-steroidal inflammatory drugs act?
COX - cyclo-oxygenase enzyme
What does activation of plasma factors include?
cleavage
enzymes
What is bradykinin similar to?
histamine
What are the roles of bradykinin?
Important role in activating complement
Increase vascular permeability
Stimulate nerves – pain
Induce expression of cytokines and chemokine
Induce production of chemical mediators of inflammation
What is the hageman factor?
enzyme in plasma
What innate immune cell engages in the kinin system?
neutrophil
What factor is part of both pathways?
factor Xa
Where is tPA (tissue plasminogen activator) found?
endothelial cells
What protein activates all plasma systems?
hageman factor
Swelling (tumor), one of the cardinal signs of acute inflammation is caused by leakage from capillaries of which factors?
plasma proteins
