Inflammation
Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. Inflammation is characterized by the following quintet: redness (rubor), heat (calor), swelling (tumor), pain (dolor) and dysfunction of the organs involved (functio laesa). The first four characteristics have been known since ancient times and are attributed to Celsus; functio laesa was added to the definition of inflammation by Rudolf Virchow in 1858.
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Characteristics
The redness and heat are caused by the increased blood supply to the affected area. Blood vessels are vasodilated upstream of an infection while capillary permeability to the affected tissue is increased, resulting in a loss of blood plasma. Vasoconstriction downstream of the infection further increases edema or swelling. The swelling distends the tissues, compresses nerve endings, and thus causes pain. The white blood cells or leucocytes take on an important role in inflammation; they extravasate from the capillaries into tissue, and carry on as phagocytes picking up bacteria and cellular debris. They may also aid by walling off an infection and preventing its spread.
If inflammation of the affected site persists, released cytokines IL-1 and TNF will activate endothelial cells to upregulate receptors VCAM, ICAM-1, E-selectin, and L-selectin for various immune cells. Receptor upregulation increases extravasation of neutrophils, monocytes, activated T-helper and T-cytotoxic, and memory T and B cells to the infected site.
Leukocytes and cytokines
Various leukocytes are involved in the initiation and maintenance of inflammation. These cells can be further stimulated to maintain inflammation through the action of adaptive cascade through lymphocytes: T cells, B cells, and antibodies. These inflammation cells are:
- Mast cells which release histamine and prostaglandin in response to activation of stretch receptors. This is especially important in cases of trauma.
- Macrophages which release TNF-α, IL-1 in response to activation of toll-like receptors.
Outcomes
The outcome in a particular circumstance will be determined by the tissue in which the injury has occured, and the injurious agent that is causing it.
There are three possible results to inflammation:
- Resolution would be the complete reconstitution of damaged tissue, it does not usually occur in the body.
- Connective tissue scarring. Some 24 hours after inflammation first occured the healing response will commence, this response involves the formation of connective tissue to bridge the gap caused by injury, and the process of angiogenesis which is the formation of new blood cells, to provide nutrients to the newly formed tissue. Often healing can not occur completely and a scar will form, for example after laceration to the skin, a connective tissue scar results which does not contain any specialised structues such as hair or sweat glands.
- Ongoing or chronic inflammation. If the injurious agent continues chronic inflammation will ensue, this is marked by inflammation lasting many days, months or even years. It is characterised by a dominating precense of macrophages in the injured tissue, which extravasate via the same methods disccussed above (ICAM-1 VCAM-1). These cells are powerful defensive agents of the body, but the toxins they release including ROS (reactive oxygen species) are injurious to our own tissues as well as invading agents. This is why chronic inflammation is almost always accompanied by tissue destruction. Finally abscess formation can ensue in chronic inflammation (abscess being a collection of pus).
Systemic inflammation
Sepsis
When inflammation overwhelms the whole organism, systemic inflammatory response syndrome (SIRS) is diagnosed. When it is due to infection, the term sepsis is applied. Vasodilation and organ dysfunction are serious problems that may lead to death.
Low-grade
With the discovery of interleukins, another concept of systemic inflammation developed. Although the processes involved are identical, this form of inflammation is not confined to a particular tissue but involves the endothelium (lining of blood vessels) and many other organ systems. The role of systemic inflammation as a cause and/or result of insulin resistance and atherosclerosis is the subject of intense research. It has little direct bearing on clinical care.