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PATHOLOGY
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rapidity of the blood circulation has become greatly diminished. The polymorpho-nuclear leukocytes are seen in great numbers in the blood vessels.

In health these cells, belonging to our first army of defenders, are found continually circulating in the blood stream in fairly large numbers; they are ever ready to rush to the point of attack, where they at once leave the blood stream by passing through the vessel walls—emigration—into the tissues of the danger zone. There they show marked phagocytosis, attacking and taking up into their interior and destroying the micro-organisms in large numbers. At the same time large numbers of these cells perish in the struggle, but even the death of these cells is of value to the body, as in the process of breaking down there are set free ferments which not only act detrimentally to the bacteria, but also may stimulate the bringing forward of another form of cell defenders—the mononuclear leukocyte.

To replace this cellular destruction there has been a demand for reinforcements on the home centres of the polymorpho-nuclear leukocytes—the bone marrow. This call is immediately answered by an active proliferation and steady maturing of the myelocytes in the marrow to form the polymorpho-nuclear leukocytes. These then pass into the blood stream in very large numbers, and appear to be specially attracted to the point of injury by a positive chemiotactic action. This phenomenon, called chemiotaxis, has been studied by several investigators. Leber experimented with several chemical compounds to find what reaction they had on these cells; by using fine glass tubes sealed at the outer end and containing a chemical substance, and by introducing the open end into the blood vessels he found that the leukocytes were attracted—positive chemiotaxis—by the various compounds of mercury, copper, turpentine, and other substances. That quinine, chloroform, glycerin, alcohol, with others, had no attractive influence on them—negative chemiotaxis. It was also found that a weak solution may have a marked positive attraction whilst a strong solution of the same substance will have the opposite effect. It has been proved that the pyo-genic bacterial toxins, if not too concentrated, will attract the polymorpho-nuclear leukocytes, but if concentrated, may have a repelling influence.

Then we have the property of adaptation, in which the negative reaction may be changed into a positive; a given toxin may at first repel the cell, but by a gradual process the cell becomes accustomed to such a toxin and will move towards it.

On reaching the vicinity they leave the blood stream and join in the warfare—many performing their function of phagocytosis (q.v.), others falling victims to the toxins. The tissues of the part become disorganized or destroyed, and their place is taken by the mass of warring cellular elements now recognized as pus.

As soon as the fluids and the polymorpho-nuclear leukocytes have succeeded in diminishing the virulence of the micro-organism, the second line of defenders—the large mononuclear leukocytes (fig. 23, Pl. II.) make their appearance at the field of battle in ever increasing numbers. These are amoeboid cells and are extremely phagocytic, their power of digestion being greatly developed. Their principal function is to bring about the removal of foreign, dead or degenerating material. This they take up into their protoplasm, where it is rapidly digested by being acted on by some intracellular digestive ferment (fig. 31, Pl. III.). Where the material is too large to be taken up by an individual cell, the dissolution is brought about by the cells surrounding the material, to which they closely apply themselves, and by the secreting of the ferment, a gradual process of erosion is brought about with ultimate absorption.

If the abscess be deeply situated in some tissue and not able to open on to a free surface so allowing the contents to be drained off, the phagocytic cells play a very prominent part in the resolution of the abscess. They are seen pushing their way right into the field of conflict and greedily ingesting both friends and foes. The first defenders, the polymorpho-nuclear leukocytes, having performed their functions, are of no more use to the organism and are therefore removed by the mono-nuclear phagocytes as useless material (fig. 31, Pl. III.).

The tissues having now mobilized an army that completely surrounds the fighting zone, there is a gradual and general advance made from all sides. The vanguard of this advancing army is composed of a more or less compact layer of the mono-nuclear phagocytes (polyblasts) accompanied by numerous new vessels. These phagocytic cells carry out the complete removal of all the injured warring elements and the damaged tissues of the part. The vessels are only temporary channels by which is brought forward the food supply that is needed by the advancing army if it is successfully to carry on its function; they probably also drain off the deleterious fluid substances formed by the cellular disintegration that has taken place in the part. Closely on the advance of this army of phagocytes or scavenger cells follows the third line of defenders, the connective tissue cells or fibroblasts.

All these cells are probably of local origin and are now stimulated to make good the damage. The connective tissue cells or fibroblasts (fig. 32, Pl. III.) are seen in active proliferation around the phagocytic zone. First they are round or oval in shape; later they become spindle shaped, arranging themselves in layers. Then they develop definite fibrils which differentiate into fibrous laminae forming a zone which shuts off the abscess from the healthy tissue and so prevents the further invasion and injurious effects of the microorganism. By the aid of the new fibroblasts this fibrous tissue zone gradually encroaches on the pus area and replaces the phagocytic layer of cells as they proceed with the absorption of the pus mass (fig. 33, Pl. III.). When complete removal of the pus mass has been accomplished by the process of absorption, the damaged area is replaced by the new fibrous tissue, which later becomes condensed and forms the cicatricial or scar tissue (fig. 35, Pl. III.)—a healed abscess.

Wounds.—The healing of wounds is brought about by similar processes to that seen in the evolution of an abscess.

If the injury be a small incised wound through the skin and subcutaneous tissues without any septic contamination, there usually follows a minimum of reaction on the part of the tissues. As the edges of the wound are brought into accurate apposition there is little or no blood lodged between them, so that an extremely narrow strip of fibrin glues the cut edges together. This strip is rapidly replaced, mainly by the connective tissue cells of the adjoining tissue growing across the temporary filled breach and firmly uniting the two cut surfaces. The vascular changes are practically absent in healing by first intention.

Healing by second intention, or granulation, is usually seen where there has been loss of tissue, or extensive damage. The reactions of the tissues vary in degrees according to the nature and severity of the injury. In resenting such insults, a remarkable uniformity and regularity in the processes is brought about by the different cells and fluids of the healthy tissues of the body. Although we have not reached a stage of certainty regarding their origin, function and destiny, recent investigations have brought forward evidence to elucidate the importance of the part played by the different cells in the various types of the inflammatory process.

If there be a loss of tissue brought about by severe injury to the skin and the deeper tissues, there is usually an extravasation of blood from the severed vessels. Along with the exuded serum this fills up the breach in the tissues and the whole is rapidly formed into a fibrinous mass due to the disintegration of the polymorpho-nuclear leukocytes setting free their ferment. The ferment thus set free brings about the coagulation of the serum, which acts as a protective and temporary scaffolding to the injured tissues. Lying between the fibrin mass and the healthy tissues is a zone of injured and degenerated tissue elements, the result of the trauma.

As early as six hours after the injury the polymorpho-nuclear leukocytes are seen passing in large numbers from the dilated and congested blood vessels of the tissues at the margin of the wound into the injured zone, where they carry on an active phagocytosis. It is believed also that they secrete bactericidal substances and ferments which bring about the liquefaction of the fibrin and the damaged tissues—histolysis—and thus assist the process of absorption. They appear to prepare the injured zone for the coming of the next series of cells. Their function being at an end they give way to these cells which carry on the process of absorption.

In a period varying from twenty-four to thirty hours there is marked evidence of the removal of the degenerated cellular elements in the damaged zone by the mono-nuclear phagocytes. Numerous fibroblasts, together with polyblasts, are visible in the fibrin mass, and the vessels at the periphery of the damaged zone are now seen to be sending out offshoots which assist in the process of absorption. These vascular buds grow out in various directions as little solid projections of cells; they then become channelled and form the new but temporary meshwork.

After two to four days these processes are more clearly emphasized. By these processes we reach the stage where the fibrin mass and damaged tissues have been completely removed, and replaced by a temporary vascular and cellular tissue, known as granulation tissue (fig. 34, Pl. III.), which in turn has to give way to the more firm and differentiated fibrous tissue. By this time the skin epithelium may have grown over the wound.

After five to seven days we find the connective tissue cells taking the principal part in the building up of the new permanent tissue, for at this stage there is an active proliferation of the fibroblasts. These cells of various shapes are seen in large numbers, mainly lying in a direction parallel to the new vessels and capillaries, which all run at right angles to the wound surface. The branching processes of these cells apparently anastomose with one another and form a delicate supporting network. It is from these cells that the fine fibrillar substance is formed, and from this stage onwards—eight to fifteen days—there is a steady increase in the new fibrils, giving more density to the new tissue. At the same time there is brought about an alteration in the arrangement of the position of the fibroblasts. These become spindle shaped with their long axis more and more assuming a position at right angles to the vessels (fig. 34, Pl. III.); the two edges of the wound are thus more firmly bound together. As their fibrils become more developed they gradually form fibrous laminae which are laid down first in the deeper part of the wound. When this process has reached a certain stage and all the absorption necessary has occurred the new blood vessels, from the increasing pressure of the successive fibrous layers, gradually dwindle and become obliterated, i.e. at a period corresponding to