Inflammation

Redness (rubor)

An acutely inflamed tissue appears red, for example, skin affected by sunburn, cellulitis due to bacterial infection or acute conjunctivitis. This is due to dilatation of small blood vessels within the damaged area ( Fig. 9.1 ).

Heat (calor)

Increase in temperature is seen only in peripheral parts of the body, such as the skin. It is due to increased blood flow (hyperaemia) through the region, resulting in vascular dilatation and the delivery of warm blood to the area. Systemic fever, which results from some of the chemical mediators of inflammation, also contributes to the local temperature.

Swelling (tumor)

Swelling results from oedema — the accumulation of fluid in the extravascular space as part of the fluid exudate — and, to a much lesser extent, from the physical mass of the inflammatory cells migrating into the area ( Fig. 9.2 ). As the inflammation response progresses, formation of new connective tissue contributes to the swelling.

Pain (dolor)

For the patient, pain is one of the best-known features of acute inflammation. It results partly from the stretching and distortion of tissues due to inflammatory oedema and, in particular, from pus under pressure in an abscess cavity. Some of the chemical mediators of acute inflammation, including bradykinin, the prostaglandins and serotonin, are known to induce pain.

Loss of function

Loss of function, a well-known consequence of inflammation, was added by Virchow (1821–1902) to the list of features drawn up by Celsus. Movement of an inflamed area is consciously and reflexly inhibited by pain, while severe swelling may physically immobilise the tissues.

Features of the fluid exudate

The increased vascular permeability means that large molecules, such as proteins, can escape from vessels. Hence, the exudate fluid has a high protein content of up to 50 g/L. The proteins present include immunoglobulins, which may be important in the destruction of invading microorganisms, and coagulation factors, including fibrinogen, which result in fibrin deposition on contact with the extravascular tissues. Hence, acutely inflamed organ surfaces are commonly covered by fibrin: the fibrinous exudate . There is a considerable turnover of the inflammatory exudate; it is constantly drained away by local lymphatic channels to be replaced by new exudate.

Ultrastructural basis of increased vascular permeability

The ultrastructural basis of increased vascular permeability was originally determined using an experimental model in which histamine, one of the chemical mediators of increased vascular permeability, was injected under the skin. This caused transient leakage of plasma proteins into the extravascular space. Electron microscopic examination of venules and small veins during this period showed that gaps of 0.1 to 0.4 µm in diameter had appeared between endothelial cells. These gaps allowed the leakage of injected particles, such as carbon, into the tissues. The endothelial cells are not damaged during this process. They contain contractile proteins such as actin, which, when stimulated by the chemical mediators of acute inflammation, cause contraction of the endothelial cells, pulling open the transient pores. The leakage induced by chemical mediators, such as histamine, is confined to venules and small veins. Although fluid is lost by ultrafiltration from capillaries, there is no evidence that they too become more permeable in acute inflammation.

Other causes of increased vascular permeability

In addition to the transient vascular leakage caused by some inflammatory stimuli, certain other stimuli, for example, heat, cold, ultraviolet light and x-rays, bacterial toxins and corrosive chemicals, cause delayed prolonged leakage. In these circumstances, there is direct injury to endothelial cells in several types of vessel within the damaged area ( Table 9.1 ).

Tissue sensitivity to chemical mediators

The relative importance of chemical mediators and of direct vascular injury in causing increased vascular permeability varies according to the type of tissue. For example, vessels in the central nervous system (CNS) are relatively insensitive to the chemical mediators, while those in the skin, conjunctiva and bronchial mucosa are exquisitely sensitive to agents such as histamine.

Margination of neutrophils

In the normal circulation, cells are confined to the central (axial) stream in blood vessels, and do not flow in the peripheral (plasmatic) zone near to the endothelium. However, loss of intravascular fluid and increase in plasma viscosity with slowing of flow at the site of acute inflammation allow neutrophils to flow in this plasmatic zone.

Adhesion of neutrophils

The adhesion of neutrophils to the vascular endothelium that occurs at sites of acute inflammation is termed ‘pavementing’ of neutrophils. Neutrophils randomly contact the endothelium in normal tissues, but do not adhere to it. However, at sites of injury, pavementing occurs early in the acute inflammatory response and appears to be a specific process occurring independently of the eventual slowing of blood flow. The phenomenon is seen only in venules.

Increased leucocyte adhesion results from interaction between paired adhesion molecules on leucocyte and endothelial surfaces. There are several classes of such adhesion molecules: some of them are made more active by a variety of chemical inflammatory mediators which therefore promote leucocyte–endothelial adhesion as a prelude to leucocyte emigration.

Neutrophil emigration

Leucocytes migrate by active amoeboid movement through the walls of venules and small veins, but do not commonly exit from capillaries. Electron microscopy shows that neutrophil and eosinophil polymorphs and macrophages can insert pseudopodia between endothelial cells, migrate through the gap so created between the endothelial cells, and then on through the basal lamina into the vessel wall. The defect appears to be self-sealing, and the endothelial cells are not damaged by this process.