Inflammation

The cellular injury resulting in inflammation may be caused by changes in temperature, ischaemia/reperfusion, infection or ionizing radiation, but the tissue response is very similar. Injured cells release mediators that are recognized by local stromal, endothelial and haemopoietic cells such as macrophages and lymphocytes. These response cells (sometimes referred to as the leucoendothelial system) in turn release inflammatory mediators. These mediators cause vasodilatation, increased capillary permeability with fluid and protein leak, and extravascular sequestration of large

Inflammatory mediator

Inflammatory mediator

Neutrophil adhesion

Figure 11.9. A schematic illustration of a capillary vessel during early inflammation. The endothelial cells express receptors which bind to neutrophil adhesion molecules. The firm adhesion results in neutrophil activation with release O2 radicals and other mediators. The result will be endothelial cell activation and contraction with leakage of plasma into interstitial spaces.

Neutrophil adhesion

Capillary leak

Figure 11.9. A schematic illustration of a capillary vessel during early inflammation. The endothelial cells express receptors which bind to neutrophil adhesion molecules. The firm adhesion results in neutrophil activation with release O2 radicals and other mediators. The result will be endothelial cell activation and contraction with leakage of plasma into interstitial spaces.

numbers of neutrophils and macrophages in the injured area. The aim of inflammation is healing of injured tissues and host defense. Cellular debris and foreign antigen are phagocytosed and destroyed. Antigen may be presented to lymphocytes to produce memory cells for an enhanced response on a second exposure to the antigen. Inflammation can further be described as local and/or systemic (Fig. 11.9).

Local inflammation

The clinical signs of local inflammation have been described by Celsus (25 AD): 'Notae vero inflammationis sunt quattuor rubor et tumor cum calore et dolore', with Galen (AD 170) later adding 'Functio laesa' to the definition. If the injurious agent is removed or overcome by the local inflammatory response, the inflammation will subside with complete restitution of the original architecture and function of the injured tissue (resolution), or when tissue had been destroyed, with the formation of scar tissue. Persistence of injury will result in chronic inflammation with gradual destruction to tissues caused by the inflammatory process. Should the body mount an inadequate inflammatory response, poor wound healing and uncontrolled infection may result. Under certain conditions a normal or exaggerated local inflammatory process can become deleterious; for example, intracranial inflammatory oedema after head injury, inflammatory bowel disease and laryngeal oedema in croup.

Systemic inflammation

In addition to local inflammation, tissue trauma and severe infection cause a systemic response expressed as tachycardia, fever or hypothermia, tachypnoea and evidence of inadequate organ perfusion or organ dysfunction. The systemic response to infection has traditionally been defined as sepsis. However, what was traditionally regarded as 'sepsis' is in fact a systemic inflammatory response mounted by the host. In up to 50% of patients who appear 'septic' no source of infection can be found. This systemic inflammatory response can also result from several other insults such as acute pancreatitis, major trauma, burns, ischaemia/reperfusion (e.g. repair of abdominal aortic aneurysm) and haemorrhagic shock (e.g. massive gastrointestinal bleed). It is best to use the term systemic inflammatory response syndrome (SIRS) to describe the systemic inflammatory response common to a variety of clinical insults and to reserve the term sepsis for the systemic response to proven infection. The underlying mechanisms of SIRS are the same as those responsible for creating local inflammation (i.e. endothelial cells, circulating blood cells and inflammatory mediators). There is generalized vasodilatation, capillary leak with extravasation of fluid into extracellular spaces, and inflammatory cells can be found sequestered in virtually all organs. It is unclear whether this systemic inflammation is beneficial to the host. What is clear is that excessive systemic inflammation results in acute lung injury with pulmonary oedema and the adult respiratory distress syndrome (ARDS), as well as renal failure, liver failure and cardiac dysfunction; that is, so-called multiple organ failure (MOF).

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