Inflammation

2 Inflammation



Inflammation is the local physiological response to tissue injury. It is not, in itself, a disease, but is usually a manifestation of disease. Inflammation may have beneficial effects, such as the destruction of invading micro-organisms and the walling-off of an abscess cavity, thus preventing spread of infection. Equally, it may produce disease; for example, an abscess in the brain would act as a space-occupying lesion compressing vital surrounding structures, or fibrosis resulting from chronic inflammation may distort the tissues and permanently alter their function.


Inflammation is usually classified according to its time course as:




The two main types of inflammation are also characterised by differences in the cell types taking part in the inflammatory response.



ACUTE INFLAMMATION








Acute inflammation is the initial tissue reaction to a wide range of injurious agents; it may last from a few hours to a few days. The process is usually described by the suffix ‘-itis’, preceded by the name of the organ or tissues involved. Thus, acute inflammation of the meninges is called meningitis. The acute inflammatory response is similar whatever the causative agent.



CAUSES OF ACUTE INFLAMMATION


The principal causes of acute inflammation are:













ESSENTIAL MACROSCOPIC APPEARANCES OF ACUTE INFLAMMATION


The essential physical characteristics of acute inflammation were formulated by Celsus (30 BC-AD 38) using the Latin words rubor, calor, tumor and dolor. Loss of function is also characteristic.








EARLY STAGES OF ACUTE INFLAMMATION


In the early stages, oedema fluid, fibrin and neutrophil polymorphs accumulate in the extracellular spaces of the damaged tissue. The presence of the cellular component, the neutrophil polymorph, is essential for a histological diagnosis of acute inflammation. The acute inflammatory response involves three processes:






Changes in vessel calibre


The microcirculation consists of the network of small capillaries lying between arterioles, which have a thick muscular wall, and thin-walled venules. Capillaries have no smooth muscle in their walls to control their calibre, and are so narrow that red blood cells must pass through them in single file. The smooth muscle of arteriolar walls forms precapillary sphincters which regulate blood flow through the capillary bed. Flow through the capillaries is intermittent, and some form preferential channels for flow while others are usually shut down (Fig. 2.2).



In blood vessels larger than capillaries, blood cells flow mainly in the centre of the lumen (axial low), while the area near the vessel wall carries only plasma (plasmatic zone). This feature of normal blood flow keeps blood cells away from the vessel wall.


Changes in the microcirculation occur as a physio-logical response; for example, there is hyperaemia in exercising muscle and active endocrine glands. The changes following injury which make up the vascular component of the acute inflammatory reaction were described by Lewis in 1927 as ‘the triple response to injury’: a flush, a flare and a wheal. If a blunt instrument is drawn firmly across the skin, the following sequential changes take place:






The initial phase of arteriolar constriction is transient and probably of little importance in acute inflammation.


The subsequent phase of vasodilatation (active hyperaemia) may last from 15 mins to several hours, depending upon the severity of the injury. There is experimental evidence that blood flow to the injured area may increase up to ten-fold.


As blood flow begins to slow again, blood cells begin to flow nearer to the vessel wall, in the plasmatic zone rather than the axial stream. This allows ‘pavementing’ of leukocytes (their adhesion to the vascular epithelium) to occur, which is the first step in leukocyte emigration into the extravascular space.


The slowing of blood flow which follows the phase of hyperaemia is due to increased vascular permeability, allowing plasma to escape into the tissues while blood cells are retained within the vessels. The blood viscosity is, therefore, increased.



Increased vascular permeability


Small blood vessels are lined by a single layer of endothelial cells. In some tissues, these form a complete layer of uniform thickness around the vessel wall, while in other tissues there are areas of endothelial cell thinning, known as fenestrations. The walls of small blood vessels act as a microfilter, allowing the passage of water and solutes but blocking that of large molecules and cells. Oxygen, carbon dioxide and some nutrients transfer across the wall by diffusion, but the main transfer of fluid and solutes is by ultrafiltration, as described by Starling. The high colloid osmotic pressure inside the vessel, due to plasma proteins, favours fluid return to the vascular compartment. Under normal circumstances, high hydrostatic pressure at the arteriolar end of capillaries forces fluid out into the extravascular space, but this fluid returns into the capillaries at their venous end, where hydrostatic pressure is low (Fig. 2.3). In acute inflammation, however, not only is capillary hydrostatic pressure increased, but there is also escape of plasma proteins into the extravascular space, increasing the colloid osmotic pressure there. Consequently, much more fluid leaves the vessels than is returned to them. The net escape of protein-rich fluid is called exudation; hence, the fluid is called the fluid exudate.




Formation 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 immunoglobu-lins, which may be important in the destruction of invading micro-organisms, and coagulation factors, including fibrinogen, which result in fibrin deposition on contact with the extravascular tissues. Hence, acute 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.









Neutrophil emigration


Leukocytes migrate by active amoeboid movement through the walls of venules and small veins, under the influence of C5a and leukotriene-B4, 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.





CHEMICAL MEDIATORS OF ACUTE INFLAMMATION


The spread of the acute inflammatory response following injury to a small area of tissue suggests that chemical substances are released from injured tissues, spreading outwards into uninjured areas. Early in the response, histamine and thrombin released by the original inflammatory stimulus cause upregulation of P-selectin and platelet activating factor (PAF) on the endothelial cells lining the venules. Adhesion molecules, stored in intracellular vesicles, appear rapidly on the cell surface. Neutrophil polymorphs begin to roll along the endothelial wall due to engagement of the lectin-like domain on the P-selectin molecule with sialyl Lewisx carbohydrate ligands on the neutrophil polymorph surface mucins. This also helps platelet activating factor to dock with its corresponding receptor which, in turn, increases expression of the integrins lymphocyte function-associated molecule-1 (LFA-1) and membrane attack complex-1 (MAC-1). The overall effect of all these molecules is very firm neutrophil adhesion to the endothelial surface. These chemicals, called endogenous chemical mediators, cause:







Chemical mediators released from cells









Dec 12, 2016 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Inflammation
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