Acute Inflammation

The classical signs are:

LOSS OF FUNCTION (functio laesa).

These gross signs are explained by changes occurring at microscopic level. Three essential features are:

Hyperaemia

The hyperaemia in inflammation is associated with the well known microvascular changes which occur in Lewis’ triple response – a FLUSH, a FLARE and a WEAL. It occurs when a blunt instrument is drawn firmly across the skin and illustrates the vascular changes occurring in acute inflammation.

The stroke is marked momentarily by a white line due to vasoconstriction.

The flush, a dull red line, immediately follows and is due to capillary dilatation.

The flare, a bright red irregular surrounding zone, is due to arteriolar dilatation.

hyperaemia explains the classical signs of redness and heat.

Exudation

Exudation is the increased passage of protein-rich fluid through the vessel wall into the interstitial tissue. It explains the weal in Lewis’ triple response.

Mechanism

1. Protein passage

2. Fluid movement

Emigration of Leucocytes

Neutrophils and mononuclears pass between the endothelial cell junctions by amoeboid movement through the venule wall into the tissue spaces. In this process both neutrophils and endothelial cells are activated and both express cell adhesion molecules, initially

Chemotaxis

The initial margination of neutrophils and mononuclears is potentiated by slowing of blood flow and by increased ‘stickiness’ of the endothelial surface.

After penetration of the vessel wall, the subsequent movement of the leucocytes is controlled by chemotaxis. The cell moves in response to an increasing concentration gradient of the particular chemotactic agent, usually a protein or polypeptide.

Important examples of chemotactic agents are:

The leucocytes move by extension of an anterior pseudopod with attachment to extracellular matrix molecules such as fibronectin using cell adhesion molecules. The cell body is then pulled forward by actin and myosin filaments.

Phagocytosis

This is the process by which neutrophils and macrophages clear the injurious agent. It is an important defence mechanism in bacterial infections particularly.

There are 3 families of opsonin.

The opsonic activity is enhanced when it is confined within a solid organ or rigid medium such as a fibrin network; where conditions are looser and more fluid, activity is diminished.

Chemical Mediators

Various chemical mediators have roles in the inflammatory process. They may be circulating in plasma and require activation or they may be secreted by inflammatory cells. Many of these mediators have overlapping actions.

Mediators dervived from:

1. Inflammatory cells

2. Plasma. These pathways are all interrelated.

Resolution

This means the complete restoration of normal conditions after the acute inflammation. The three main features which potentiate this sequel are:

Resolution of lobar pneumonia (bacterial inflammation of lung alveoli) is a good example:

Following bacterial kill the mechanism is as follows:

Suppuration

This means the formation of PUS; where pus accumulates an ABSCESS forms.

Infection by pyogenic (pus-forming) bacteria is the usual cause, e.g. staphylococcal abscess (or boil). The pus in this case is a thick, creamy yellow fluid which, on centrifugation, separates thus:

Evolution of an Abscess

The usual evolution of an abscess is as follows:

When the abscess is deep-seated, the process may be modified as follows:

Organisation and Fibrosis

Organisation occurs when, during the acute inflammatory process, (a) there is excessive exudation or necrosis or (b) when local conditions are unfavourable for the removal of exudate and debris. The term also applies to the local reaction to the presence of thrombus and also the necrosis associated with infarction.

The changes are similar to those described in wound healing viz – the growth of new capillaries into the inert material (exudate or thrombus), the migration of macrophages and the proliferation of fibroblasts resulting in fibrosis.

A good example of organisation following acute inflammation is seen in the pleura overlying pneumonia. The inflammation of the lung tissue proper usually resolves completely (p.264); in contrast the pleural exudate is not easily removed and organisation takes place.

Other good examples of organisation are seen after infarction (see p.166).

Granulomatous Inflammation

This is the term given to forms of chronic inflammation in which modified macrophages (epithelioid cells) accumulate in small clusters surrounded by lymphocytes. The small clusters are called granulomas. The basic lesion in tuberculosis is a good example.

Similar granulomas are seen in:

N.B. In all of these granulomatous diseases the basic lesion may be identical, but caseation only occurs in tuberculosis.

The epithelioid cells of the granulomas are modified macrophages, and giant cells are derived from macrophages usually by cell fusion but occasionally by nuclear division without cytoplasmic separation.

The Langhans’ giant cell – seen in chronic granulomata, e.g. tuberculosis and sarcoidosis.

The foreign body giant cell – seen in association with particulate insoluble material.

Mechanism of Granuloma Formation

Sinus

A sinus is a tract lined usually by granulation tissue leading from a chronically inflamed cavity to a surface. In many cases the cause is the continuing presence of ‘foreign’ or necrotic material.

Examples include:

• Sinuses associated with osteomyelitis (inflammation of bone).

Where necrosis of bone occurs, chronic sinuses form over it.

Fistula

A fistula is a track open at both ends, through which abnormal communication between two surfaces is established.

There are two main types:

2. Acquired – due to:

An EMPYEMA is a collection of pus in a body cavity or hollow organ. The term refers usually to the pleural cavity or the gall bladder.

CELLULITIS occurs when inflammation spreads in the connective tissue planes.