Accute Inflammation Flashcards
What is acute inflammation the driving force of?
The innate Immune response
- The response of living tissue to infection/damage
- Acute inflammation is the initial and essential process for innate immunity
How quickly does acute inflammation develop and how long does it last?
Develops quickly (mins-hours) and lasts a few hors to days
What are the 3 main interlinked processes of acute inflammation?
- Vascular dilation (change in blood vessel calibre)
- Increased vascular permeability - allows for cells and molecules to support inflammatory response
- Neutrophil activation and migration
What are the 4 main causes of acute inflammation?
Microbial infection
- Inflammation can be induced by microorganisms
Physical agents
- Physical trauma
- UV or other ionising radiation
- Heat (burns) or cold (frostbite)
Irritant and corrosive chemicals
- Acids and alkalis
- oxidising agents
- Infective agents may release specific chemical irritants which lead directly to inflammation
Tissue necrosis
- Lack of oxygen or nutrients due to inadequate blood flow (infarction)
What are the cardinal signs of acute inflammation according to Celsus?
Rubor (redness) - due to dilation of small blood vessel in damaged areas
Calor (heat) - due to increased blood flow (hyperaemia)
Tumor (swelling) - due to accumulation of fluid in extra vascular space (oedema)
Dolor (pain) - Stretching/distortion of tissue due to oedema. Chemical mediators bradykinin, prostaglandins induce pain
Loss of function - related to chronic inflammation
What are the vascular responses of acute inflammation?
- Small blood vessels adjacent to site of damage become dilated with increased blood flow
- Endothelial cells swell and partially retract - opening up of gaps between them
- Exudation - the vessels become ‘leaky’ and allow passage of water, salts and some proteins (blood flow slows)
- Endothelial cells activated to promote immune cells passage to damage tissues (mainly neutrophils and monocytes/macrophages)
- The endothelial cells can change what they express on their surfaces to change what they are attracting - so they can attract immune cells
What is the process involved in bacterial induced acute inflammation (gingivitis)?
- Bacteria trigger macrophages to release cytokines and chemokines
- Vasodilation and increased vascular permeability causes redness, heat and swelling and allows the passage of fluid and cells
- Inflammatory cells migrate into tissues, releasing inflammatory mediators that cause pain (cells and fluid aim to resolve inflammation)
What happens to capillaries in response to acute inflammation?
- Dilation of capillaries which increases the blood flow
- This is done by the opening of sphincters so a lot more blood is flowing to the area
What does oedema mean?
Excess of fluid
What does the inflammatory exudate provide to the affected tissue?
Fluids and salts
- Dilute toxins in tissues
- Allows diffusion of mediators across membranes
Glucose and oxygen
- Supports macrophages
Complement proteins and antibodies
- Opsonins for invading microorganisms - support phagocytosis
Fibrin (long insoluble filamentous protein)
- Polymerised via coagulation cascade
- Provides scaffold entrapping microbes and assist immune cell migration to area
- Important in blood clots
What are the chemical mediators of acute inflammation?
- Histamine
- Bradykinin
- Leukotrienes
- Serotonin
- Prostaglandins
What are the protein mediators of acute inflammation?
- Cytokines
- Chemokines
How is histamine formed?
Product of the breakdown of AA histidine
Where is histamine stored?
In granules of immune cells such as mast cells
How is degranulation of histidine to release histamine stimulated?
- Stimulated by C3a, C5a - complement
- Also caused by antigens
What are the roles of histamine?
- Role as neurotransmitter - itching (acts upon nerve fibres)
- Causes vascular dilation
- Multiple functions in immune response
What are prostaglandins the product of?
Fatty acid metabolism
What is the most abundant prostaglandin?
Prostaglandin E2 (PGE2)
What are the roles of prostaglandins in acute inflammation?
- Causes vascular dilation
- Regulate cytokine production from cells
- Regulate chemokine production - attracts immune cells
- Act on nerve fibres (neurotransmitter) - pain
- Involved in tissue remodelling
What are prostaglandins regulated by?
The enzyme Cyclo-oxygenase II (COX II)
What targets COX II enzyme?
NSAIDS (non steroidal anti inflammatory drugs)
What are plasma factor systems?
- Proteolytic cascades
- Stepwise activation involving formation of enzyme complexes and protein cleavage
What are the 4 plasma factors enzymatic cascades?
- Complement
- The kinin system
- Coagulation
- Fibrinolytic system
Are all 4 of the plasma factor enzymatic cascade systems interlinked?
Yes, the Hageman factor is important as it is the driver for most of these cascades
What does the Kinin system require for activation?
Activation of Hageman factor (XII –> XIIA) which occurs in response to damage on exposed surfaces
What does XIIA convert prekallikrein into in the Kinin system?
Kallikrein
What does Kallikrein convert high-molecular-weight kininogen into in the Kinin system?
Bradykinin
What are the roles of bradykinin in acute inflammation?
- Important role in activating complement
- Increased vascular permeability
- Stimulates nerves - pain
- Induce expression of cytokines and chemokines
- Induce production of chemical mediators of inflammation
What does coagulation mean?
Formation of a blood clot
What are the names of the 3 pathways in the coagulation system?
- Common
- Extrinsic
- Intrinsic
- Intrinsic and extrinsic both diverge from the common pathway
What is the intrinsic pathway of the coagulation system?
- Activated when blood comes into contact with sub-endothelial connective tissues (outside blood vessel)
What is the extrinsic pathway of the coagulation system?
- Damaged blood vessel means Human Factor VII (FVII) leaves vessel and encounters Tissue factor on surrounding tissue which activates the extrinsic pathway
What is the common pathway of the coagulation system?
Production of thrombin which in turn produces fibrin (building block of clot)
What glycoprotein is the building block of a clot?
Fibrin
What is fibrinolysis?
The enzymatic breakdown of the fibrin in blood clots
- Without the ability to break down clots we would clot to death
What is the molecule that breaks down blood clots?
Plasmin
In health what 2 processes are balanced in the relation to blood clotting?
Coagulation and fibrinolysis
What does the fibrinolytic system result in the activation of?
Plasmin
What are the roles of the fibrinolytic system?
- Activates compliment (plasmin cleaves C3)
- Indirect role as fibrin breakdown products (split products) promote vascular permeability
What does congenital mean?
Born with it
What are the 3 congenital coagulation disorders?
- Von Willebrand Disease
- Haemophilia A
- Haemophilia B
What is meant by a congenital coagulation disorder?
Deficiency or lack of specific clotting factor
What Clotting factor is a person lacking if they have Von Willebrand disease?
Deficiency in Von Willebrand factor (protein which binds factor VIII and stabilises - lack of VWF leads to low levels of factor VIII)
- This is not a life threatening disease but need to be careful if need any potential surgery as can bleed very heavily
What clotting factor is a person lacking if they have Haemophilia A?
Deficiency in factor VIII
What clotting factor is a person lacking if they have Haemophilia B?
Deficiency in factor IX
What drugs cause acquired coagulation disorders?
- Warfarin - anti-coagulant - inhibits numerous coagulation factors
- Heparin - anti-coagulant - potentiates antithrombin
What does sequelae mean?
The outcome
What does the outcome of the pathways of coagulation depend upon?
- Tissues involved
- Amount of tissue destruction
- Nature of the injurious agent (what is causing it?)
What is suppuration?
The formation of pus (abscess)
What is pyogenic bacteria?
Puss forming bacteria
What is suppuration caused by?
Neutrophil infiltration which function to eliminate bacteria
What is pus?
Bacteria with dead and dying neutrophils
How is the spread of bacteria reduced by the process of pus formation?
- Once pus accumulates it is surrounded by a pyogenic membrane - the body will try to wall off with membrane - abscess
- Bacteria within an abscess relatively inaccessible also prevents spread
What are the 3 types of dental abscess?
- Gingival
- Periodontal
- Periapical
What is the definition of resolution in reference to acute inflammation?
The complete restoration of tissues after an episode of acute inflammation
What does resolution 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
