1.03 - Inflammation Flashcards
What is Inflammation?
Body’s response to injury
Part of the innate immune response
Limit and then repair damage cause by an injurious agent
It is primarily a protective response, which leads to repair
What are the macroscopic signs of inflammation?
Redness Swelling Heat Pain Loss of Function
What occurs during the acute and chronic phases of inflammation?
Acute (Minutes, Hours, Days) - Leucocytes (mainly neutrophils) - Exudate of fluid and plasma proteins Chronic (Weeks, Months, Years) - Lymphocytes and Macrophages - Proliferation of blood vessels, fibrosis, tissue necrosis
What are the components of inflammation?
Microvasculature Circulating blood cells (red-passive, white-active) Tissue cells (Secretion/release of mediators) Inflammatory mediators (numerous)
What are the changes in the microvasculature that occur in inflammation?
- Transient vasocontriction (arterioles)
- Vasodilation of all vessels –> increase blood flow
- Permeability of small vessels increases –> exudate
- Blood flow becomes sluggish (stasis)
- Leucocytes become marginated and migrate in to extravascular space
What is exudate?
exudate is any fluid that filters from the circulatory system into lesions or areas of inflammation.
Includes water, the dissolved solutes of blood, plasma proteins, white blood cells, platelets, and in the case of local vascular damage: red blood cells.
Describe Inflammatory mediators
Products of circulating blood cells, local tissue and plasma proteins
End result of combined action is attraction of more leucocytes to the site of injury and facilitation of phagocytosis of injurious agent
What are the plasma protein derived inflammatory mediators?
Complement system proteins
Coagulation, fibrinolytic and kinin system proteins
What are the cell and tissue derived inflammatory mediators?
Cytokines Arachidonic acid metabolites - Prostaglandins - Leukotrienes Histamine and other biogenic amines
What are the 5 family groups of cytokines?
Interferons (IFN) Interleukins (IL) Chemokines Colony Stimulating Factors Growth Factors
What are the functional groups classification for cytokines?
Proinflammatory (TNF, IL-1)
Anti-inflammatory (IL-10
Immunostimulatory (IL-2)
What are the cellular contributions to inflammation?
Polymorphs Mast Cells Monocytes & Macrophages Platelets Vascular Endothelial Cells Neurons
Describe the role of Polymorphs in inflammation
First to arrive
Engulf, kill (free radicals) and digest (enzymic) microbes
Describe the role of Mast Cells in inflammation
When activated (such as by complement) they secrete mediators
Describe the role of Monocytes & Macrophages in inflammation
Late arrivals
Secrete cytokines and chemokines
Engulf cell debris and microbes
Describe the role of Platelets in inflammation
Prostaglandin/leukotriene synthesis
Free radicals
Pro-inflammatory
Describe the role of Vascular Endothelial Cells in inflammation
Contract/relaxation (nitric oxide)
Also important in repair (angiogenesis)
Describe the role of Neurons in inflammation
Release compounds including Substance P (pain) & Kinins
What are the systemic sequelae of inflammation?
Increased temperature (Fever)
Increased blood leucocytes
Synthesis of plasma proteins
Symptoms and signs depend upon the total mass of inflammatory tissue
Site the inflammatory lesion is critical in giving rise to other symptoms and signs
Is there a purpose behind a fever?
Many bacteria do not live or multiply as effectively in temperatures >38 degrees C. Therefore teleologically the “purpose” is protective and to aid clearance of infecting bacterial organisms.
What different types of fever patterns are described? Are they useful diagnostically?
Many descriptive terms used. E.g. “spiking”, “nocturnal”, diurnal etc. Each gives the reader more information about “when”, “how long”, etc. The descriptions are useful clinically. E.g. in particular from of malaria, a high fever may occur every 3 to 4 days; this follows the lifecycle of that malarial parasite.
What are some of the systemic sequelae of inflammation apart form fever?
Increased heart rate, increased pulse pressure, flushing, raised white cell count etc
If you were designing pharmacological compounds to interfere with or minimise inflammation or its consequences, what sites could you target? Are there drugs which act at these sites now?
Decrease production of inflammatory compounds
- Decrease number of cells producing enzymes
- Immunosuppressants (Azathioprine)
- Glucocorticosteroids (Prednisolone)
- Decrease production of inflammatory cytokines
- NSAIDs (Aspirin/Paracetamol)
Decrease response to defined cytokines
- Antibodies to defined cytokines
- Anti-TNFalpha (infliximab)
- Decrease cellular response to cytokines by modification of nuclear response (mesalazine)
Which “inflammatory” compounds cause pain? Do they act directly on receptors or via other mechanisms?
Some of inflammatory mediators cause pain directly by being agonists for specific receptors on pain fibres. Others “facilitate” or enhance this effect, also by acting at specific receptors on pain fibres, but in the absence of the inflammatory response, they them selves do not initiate the action potential which is subsequently “felt” as pain. See Chronic inflammation lecture.
