Acute Inflammation Flashcards
Compare necrosis with apoptosis
Necrosis = pathological, group of cells, cell swelling, not energy dependant, inflammation
Apoptosis = physiological or pathological, individual cells, cell shrinkage, energy dependent, not inflammation
What is acute inflammation?
2 definitions:
1) A response to vascularised tissue to infections and tissue damage that brings cells and molecules of host defence from the circulation to the sites where they are needed, to eliminate the offending pathogens
2) Complex biological response to tissues to harmful stimuli and is a protective response involving blood vessels, immune cells and molecular mediators
Why do dentists need to know about inflammation?
1) Dental caries
2) Periodontal disease
3) Mucosal disorder
4) Dental cysts
5) Extraction
6) Antibiotics interference
All result in or cause inflammation.
What are the two types of inflammation?
1) Acute
- develops within mins-hours of noxious stimulus
2) Chronic
- takes longer
They are different in their cellular and tissue components.
Often there is a blurring of the distinction between the two is inflammation is dynamic and sometimes the balance can be shifted to either acute or chronic inflammation (told by tissue composition).
What is the puropse of inflammation?
1) Destroy/contain noxious stimulus (dilution of toxins, entry of leukocytes)
2) Initiate repair (fibrin formation)
3) Return to function (transport of nutrients and transport of drugs)
What is the broad overview of inflammtion?
Stimulus (recognition of local cells, stimulus may be microbes, necrotic tissue or APC) Recognition Vascular events Cellular events (leukocytes) Exudate (framework for healing to occur) Outcome
What are the 5 stimuli for inflammation?
1) Physical e.g. trauma, thermal, radiation
2) Chemical e.g. CO, cigarette smoke, ethanol
3) Infectious e.g. toxins, metabolic products, lysis, DNA damage
4) Oxygen deprivation e.g. hypoxia, ischaemia
5) Immunologic e.g. autoimmune
Give brief details of the recognition stage
- Phagocytosis and antigen presenting
- Mediator release
- Cells of immune systems becoming activated
- Cells killed or antibodies produced
What are the two vascular events?
Explain them
Vasodilation
Increased vascular permeability
Vasodilation: Increase in capillary size
Results from direct action on the capillary smooth muscle and endothelial cells by chemical mediators that are released as a result of tissue damage. These mediators include histamine, prostaglandins, platelet activating factor and kinins.
Vasodilation leads to a decrease in blood flow rate and causes vascular congestion. This can be seen clinically as redness and heat.
Increased vascular permeability:
Result of the gaps of the endothelial cells opening up. This results in the leakage of fluid and plasma proteins into extravascular fluid. Increase in endothelial gaps is a direct action of mediators including histamine, leukotriene, platelet activating factor and kinins.
The process by which there is net flow of fluid and plasma proteins from within the vessels to the extra vascular space is called exudation and therefore the fluid that collects in the extra vacular space is called fluid exudate.
Explain how the flow of fluid out of the capillary works
Normal fluid forms by high osmotic pressure within blood vessel resulting in flow of fluid into the extra vascular spaces. At venous ends, increased osmotic pressure in extra vascular space causes fluid to move back into vessel.
This means no net gain of fluid in extra vascular space.
In acute inflammation, due to increased vascular permeability, at the venous end there is an increased osmotic pressure in extra vascular space resulting in a net flow of fluid into the extra vascular space resulting in fluid exudate.
How do the cellular events occur in acute inflammation?
At sites of inflammation, where there is vasodilation and haemostatic dialysis, neutrophils adopt a more peripheral position in endothelial lumen, more closely related to endothelial cells.
This is called margination.
As neutrophils marginate, they are able to detect ligands expressed on endothelial cells via their receptors. Likewise, there are receptors on endothelial cells that are able to detect receptors on neutrophils.
Selectin receptors are important here, P selectin is expressed on endothelial cells and L selectin on neutrophils.
The selectins are up-regulated through the effect of cytokines including IL1 and TNF which are expressed as a result of tissue damage.
The bond between neutrophils and endothelial cells via selectins is a weak one so attachment and detachment happens. As as result, the neutrophil rolls across endothelial cell in the rolling process.
The process of rolling comes to an end when the neutrophil firmly attaches to the endothelial cell.
This is brought about be intern receptors on neutrophil surface. The ligands for these receptors are the cell adhesion molecules e.g. ICAM1 expressed on the surface on endothelial cells.
ICAM1 is expressed following the release of IL1 and TNF.
Following firm attachment of the neutrophil to the endothelial cells, the neutrophil is able to be squeezed between the gaps between the endothelial cells to exit the vessel lumen and to become part of the inflammatory exudate.
These cells form the cellular part of the exudate.
The process of transmigration does not damage the basal lamina of vessel wall. once the neutrophil has excited the blood vessel, it migrates to the site where it is most needed. Does this by attraction from chemotaxis factors. This migration of the neutrophil to the needed site is chemotaxis and chemotaxic factors include bacterial products, chemokine, complement (c5a especially) and leukotriene B4.
What are the 3 types of exudate and explain each one?
Serous exudate is the least common, characterised by a cell poor fluid formed in mucosal or skin blisters for example.
Fibrinous exudate is characterised in cases where there is significant vascular damage or bleeding e.g. tooth extraction.
Purulent exudate is also known as the supreative exudate and is characterised by a cell rich fluid (usually neutrophils). An example of this is an abscess. These are most common in bacterial infections.
What do neutrophils do at the site of inflammation once it has gone down its chemotaxic gradient?
1) Adherence and ingestion of bacterium via neutrophil - due to bacteria being opsonised. Adherence occurs by the extension of pseudopodia that are put forward by the neutrophil cytoplasm to engulf the bacterium
2. Bacterium gets maintained by a bound cytoplasmic vesicle called the phagosome.
3. Phagosome binds with a lysosome to form a phagolysosome.
- Digestion due to the enzymes found in the lysosome
Importance of this is that digestion of necrotic debris and bacteria occurs within its own membrane bound vesicle without causing damage to surrounding cytoplasm. - Following digestion, a residual body is formed
- Digestive debris is discharged
What happens within a phagolysosome?
Several ways that bacteria and necrotic debris is eliminated by neutrophils, most common is through the generation of reactive oxygen species.
These are brought about by the reduction of NADPH to NADP+ in the region of the phagolysosme membrane. In this process, the oxygen anion is formed. This then is converted to hydrogen peroxide (not too potent to bacteria). Killing is much more efficient when hydrogen peroxide reacts with myeloperoxidase. Myeloperoxidase is found within granules in the neutrophils and these merge with the phagolysosome. The combination of hydrogen peroxide and myeloperoxidase, in the presence of the chloride ion, generates hypochlorite (OCl-). This is what is the most potent.
Considering other flashcards, give an overview of inflammation now
Recognition Vasodilation Permeability Adhesion and migration Phagocytosis and killing
