Part 7

MICROBES, DIAPEDESIS AND PHAGOCYTOSIS.

The rôle of =microbes= in inflammation is much greater than was formerly supposed. It is now demonstrated that a large class of inflammations are directly caused by the colonization of microbes in the tissue and by the local irritation caused by their ptomaines and toxins. We must also admit the direct action of the latter on the heat producing and vaso-motor nervous centres, as a factor more or less potent in different cases in the causation and maintenance of inflammation. No less important is the relation of the microbe to the migration of the globules and the subsequent results of the inflammation. This influence microbes share with certain chemical agents. Migration may be greatly checked even in inflamed parts by the hypodermic or intravenous injection of sulphate of quinia, eucalyptol, salicylic acid, or iodoform. Some have thought these acted by a chemiotactic attraction, but quinia is otherwise found to repel the leucocytes. Their action on the leucocytes or capillary walls is problematic.

=Chemiotaxis= is that power by which a microbe or any element attracts or repels the leucocytes. When it attracts the chemiotaxis is said to be positive, when it repels it is negative. Among negative chemiotactic agents are quinia, solutions of sodium chloride (10%), and potassium salts, lactic acid, alcohol (10%), chloroform, glycerine, jequirity, and bile. To some agents, (creatine, creatinine, allantoin, peptone, phlorydzine,) leucocytes are indifferent. To gluten, wheat casein, pea legumin and the great majority of pathogenic microbes, leucocytes are positively attracted. As microbes exercise a great influence in producing local inflammation, so they are important factors in procuring an abundant emigration of leucocytes. Some of the most fatal of microbian diseases, like fowl cholera, repel leucocytes, and the benefit of their defensive work is to a large extent lost. The toxins of the chemiotactic microbe filtered from the bacteria exert the same influence as the living bacteria, as shown by Gabritchevski, Massart and Bordet.

But chemiotaxis may be exerted from within the bloodvessel as well as from without. Bouchard, Massart and Bordet have shown that a tube containing a culture of bacillus pyocyanus, introduced beneath the skin of a rabbit attracts in a few hours a great number of leucocytes. But if, immediately after its introduction, ten cubic centimetres of a sterilized culture of the same bacillus are injected into a vein, very few leucocytes enter the tube inserted under the skin. The chemiotaxis seems to operate in this case from within the blood, and the desires of the leucocytes are satisfied without leaving the vessel. It would seem that in such cases the migration and protective work of the leucocytes is best exerted at the outset of the illness and before the toxic products have been poured into the blood in any quantity, whereas in the advanced stages when the blood is charged with ptomaines and toxins migration and phagocytosis would be likely to be limited and ineffective. The same consideration would forbid the use of drugs that check migration in all cases of attacks by microbes for which leucocytes have a positive chemiotaxis.

=Phagocytosis= is the act by which the leucocytes englobe and dissolve the invading microbe. By its amœboid movement the leucocyte flows around, and envelopes the microbe for which it has a positive chemiotaxis, and then begins the struggle of vitality between the two living germs. If the poison (leucomaine antitoxin,) and digestive ferment (enzyme) of the leucocytes are more deadly to the invading germ, than its ptomaines, toxins and enzymes are to the leucocyte, the white cell comes off the victor, and recovery takes place, but if the converse obtains the triumph is on the side of the microbe. As a rule much depends on the more or less deadly nature of the products of the invading microbe, on the numbers of the germ, the rapidity of its proliferation, and the consequent amount of its toxic products thrown into the system, on the one hand: And on the other the potency of the chemiotaxis of the leucocyte for the invading germ, the number of white cells that emigrate into the inflamed tissue and engage in the work of phagocytosis, and on whether the particular animal system and its white cells have sustained a previous attack by the same germ and has thereby been educated to produce a greater amount of the defensive proteids (leucomaine, antitoxin, enzyme) than it naturally would (acquired immunity).

Even with an abundant emigration of the leucocytes into the inflamed or invaded tissue, a number, greater or less, are usually destroyed by the bacterial poisons and pass into degeneration or liquefaction, as in the formation of pus, and yet the attacking germ may be overcome, destroyed and devoured by the rapidly increasing survivors. In general terms the migration of the cells is in inverse ratio to the susceptibility of the animal to the microbe or the disease which it causes.

The positive and negative chemiotaxis, which determine phagocytosis or prevent it, may be seen in the action of the leucocytes toward the germs of two diseases, to one of which the animal is susceptible and to the other of which it is not. Thus the leucocytes of the pigeon take in the bacillus anthracis and suffer nothing apparently, whereas the same white cells of the dove are repelled by the bacteria of fowl cholera which are not therefore found in their interior.

The leucocytes that migrate from the bloodvessels are in the main, the most numerous, (the neutrophile or polynuclear) form; the mononuclear leucocytes with horseshoe shaped nucleus also migrate but in much fewer numbers and are as a rule less occupied in phagocytosis. At the same time, these two forms may show each a preference for a particular microbe, the polynuclear cell sometimes devouring one which the mononuclear cell rejects, and the mononuclear cell taking in one which the polynuclear refuses.

The small round white cells (lymphocytes) and the eosinophile leucocytes take no prominent part in phagocytosis.

EXUDATION.

In inflamed vascular tissues one of the most important results is the exudation. This is not, however, a mere transudation of the liquid parts of the blood, as takes place in dropsy, but it is to a large extent a selective process determined apparently by the condition of the capillary walls, and the nature of the inflammation is stated according to the character of the exudate. The dropsical effusion contains little albumen, fibrine or cell forms, and does not coagulate. The inflammation exudate contains abundance of fibrine, cells and other solids and coagulates spontaneously in contact with inflamed tissue, or when removed from the body, by reason of the transforming leucocytes. Inflammatory exudate usually contains 6 to 8 per cent. of solids whereas the normal canine lymph contains 4 to 6. The exudate varies not only in different inflammations, but in successive stages of the same inflammation. The exudate may be mucous, serous, fibrinous or hæmorrhagic.

=Mucous Exudate.= In inflammation on a mucous or synovial surface the inflammatory exudation, mingled with the more or less altered secretion of the mucous glands, and the epithelial cells and leucocytes forms a viscid fluid, rich in mucin, and characterizing the mucous or catarrhal inflammation. The nature of the discharge varies greatly, the serous character predominating at the start of the inflammation, and a thick, opaque creamy or semi-solid muco-purulent material appearing as the disease advances. It contains filaments of precipitated mucin insoluble in acetic acid or alcohol and cells in all stages of change from the exudation leucocyte and mucous cell to the pus corpuscle, the latter being characterized by its bipartite or tripartite nucleus rendered visible by contact with weak acetic acid.

=Serous Exudate.= This consists of the liquid elements of the blood with only a limited amount of fibrine formers and consequently little tendency to clot firmly. The presence of fibrinogen however serves to distinguish it from the liquid of mechanical dropsy, as does also the greater quantity of cells and nuclei of common salt and phosphates. It is usually straw colored in mass, but is sometimes slightly opalescent by reason of the numbers of cells and floating filaments of fibrine. Serous exudations take place in the early stages of inflammations (as in catarrh) and in inflammations of serous membranes (pleura, peritoneum, joints), in strong, vigorous subjects. They constitute the liquid contents of blisters whether raised by medicinal irritants, chafing, or heat. They clot under heat and nitric acid with a firmness proportionate to the amount of albumen.

These effusions are dangerous by reason of their interference with the functions of organs by pressure as with the dilatation of the lungs, the movements of the heart, the action of joints, or the integrity of the brain or spinal cord. When the causative disease has subsided they are usually speedily reabsorbed, the cells passing into the lymph vessels, or becoming degenerated, liquefied, and absorbed. Yet serous effusions often remain as permanent accumulations. For the blood staining of serous effusions and their clearing up, see under pleurisy.

=Fibrinous Exudate.= This is characterized by the amount of fibrinogen and fibro-plastin in its composition and by the comparative absence of leucocytes. It oozes through the vessels and coagulates in the tissues or on the surface of inflamed serous or mucous membranes. The more liquid part separating from the coagulum escapes from the free surface or accumulates in the lower part of the serous cavity. The coagulation is doubtless caused by the fibrine ferment derived from the rapidly proliferating cells and degenerating leucocytes. It usually occurs promptly in or on an inflamed tissue, but in contact with healthy structures only (as in a serous sac) it may remain fluid for an indefinite length of time. This exudate constitutes the false membranes that form on the pleura, pericardium or arachnoid, the coagulum of fibrinous pneumonia, and the plastic lymph on the surface of a granulating wound. It is especially injurious by reason of its enveloping organs (lungs, heart, bowels, iris) and subjecting to permanent compression by reason of its contracting, also by binding them to adjacent structures by false membranes. In coagulating it becomes first fibrillar then granular and finally undergoes molecular degeneration (Cornil and Remvier), or development into new tissue (Paget). When organized it usually takes the form of the adjacent tissue from which its trophic cells are derived. Thus in divided tendons, in serous membranes and in granulating wounds it is fibrous, and between the ends of a broken bone it is osseous. If however, the adjoining tissue is a highly organized one, like nerve or muscle it may be replaced by a simpler (fibrous, osseous).

Fibrinous inflammations are especially found in connection with inflamed fibrous tissues and in strong vigorous subjects.

=Blood Exudations.= In all inflammations there is some migration of blood globules (red as well as white) but seldom in quantity sufficient to stain the tissues materially. Minute ruptures of the capillary vessels are not uncommon, with punctiform clots in the tissues, but extensive escape of blood is mainly seen in penetrating or contused wounds of the loose, subcutaneous connective tissue, and in infective inflammations (anthrax, Rinderpest, swine plague, petechial fever, malignant catarrh, snakebites) with destruction of blood globules or extreme changes in the walls of the capillaries. Newly formed vessels in friable neoplasm are subject to blood effusions. In acute inflammations of serous membranes the exudate is usually of a dark port wine hue at first. In such cases it may pass in succession through all the stages of dark red, brick red, yellow, reddish, and chocolate color, before becoming milky and finally transparent.

=Croupous Exudate.= Croupous inflammation usually occurs on or near a mucous surface and is characterized by an exudation consisting mainly of fibrinous material entangling white cells, epithelium, a few pus corpuscles and some form of bacteria. In true diphtheria of children this is the Löffler bacillus, in the pseudodiphtheria, attending on scarlatina, etc., it is streptococcus pyogenus, in the diphtheria of calves it is bacillus diphtheriæ vitulorum, and in that of chickens and pigeons it is the bacillus diphtheriæ columbarum (Löffler). Pseudo-membranous inflammations therefore constitute a group agreeing in the nature of the exudate but differing essentially in the cause. This difference in the cause has a most material effect on the course and gravity of the disease. One form like true diphtheria in man not only extends into the tissues, and tends to necrotic changes, but also poisons the nerve centres by the toxic materials absorbed inducing troublesome paralysis, while another like croup of children establishes a violent but essentially superficial disease and when that recovers it leaves no ulterior ill effects elsewhere.

A =Chyliform exudate= has been noted in peritonitis in the dog the milky whiteness being due to fatty granules.

RESULTS AND PRODUCTS OF INFLAMMATION.

As nearly all inflammations have significant exudations it is well to follow these in their subsequent progress through reabsorption and removal, development into new tissues, necrosis, suppuration and ulceration.

=Resolution.= If an inflammation, slight in character and with only a moderate exudation, subsides and is followed by a rapid liquefaction of the cells and fibrinous coagula and a reabsorption of the exudate, so as to leave the part in its primary healthy condition structurally and functionally, it is said to have terminated by “resolution.” If this occurs with extraordinary rapidity it is said to have ended by “delitescence.” This is not always an unalloyed good, as often in delitescence, coagula and infecting material may be carried on by the circulation, to block the next set of capillaries in its course and set up new centres of inflammation. This is one form of “metastasis” though a more definite metastasis is in rheumatism where the disease attacks one joint today and a distant one to-morrow.

=Inflammatory New Formations.= Of the growths in lymph there are two principal kinds: first, the plastic, fibrinous, granular or molecular; and second, the aplastic or corpuscular. The first form tends to develop into new structure, the second to disintegrate and decay. The tendency to one or other form depends largely on the strength or weakness of the system’s health, on the deficiency or excess of corpuscles in the exuded fluid, and on the distance of the latter from living tissues and blood supply. Much also depends on the predisposition of the genus, the tendency to suppuration in lymph being in a descending series from horse, ass, and mule, through ox and sheep, to dog, pig, and finally, the bird, in which latter suppuration is quite exceptional.

=Suppuration.= In inflammations of a high type, in those occurring on the skin or mucous membranes in which there is an extraordinary increase of nuclei and embryonal cells, and in lymph thrown out in excess at one point, so that its central parts are far from vascular tissue and nourishment, the cell elements undergo a rapid increase and degradation into pus-corpuscles, and its solidified intercellular lymph undergoes granular decay and liquefaction into pus.

While the above conditions are favorable to the formation of pus, the process of suppuration must now be recognized as an infective process due to the propogation of bacteria (mainly chain forms—Streptococcus pyogenes—cluster groups—Staphylococcus pyogenes—and rod forms—Bacillus pyogenes). These or other bacteria are found in the pus of acute abscesses, and when absent in chronic abscesses are to be considered as having perished since the abscess was recent and active. Inoculation of a rabbit with an excess of the pus of an acute abscess produces general purulent infection (pyæmia) and early death; from a medium dose an abscess is produced; while from a small dose there is no effect whatever. In the latter case the bacteria are overcome and devoured by the abundance of vitally potent white blood globules and tissue cells. This pus-forming action of these bacteria explains the great difference in results in wounds exposed to the air and those in the interior of the body and far removed from air and its floating bacteria. A broken bone, with no wound in the skin and little injury to parts around the fracture, is readily repaired without any formation of pus, if merely kept still and immovable; whereas a broken bone, continuous with a wound through the skin, always tends to form pus or become otherwise infected, and is extremely dangerous even to life. The tendency of every open sore is to form pus on its surface but this may be arrested and avoided by preventing the access of germs, or by a free use of disinfectants and a covering which shall arrest and filter out the germs. Similarly in an abscess, evacuation followed by the injection of disinfectants, without the formation of any perceptible permanent opening to the outer air, will put a stop to the pus-formation. The subjection of an inflamed part to the control of these pus-forming bacteria is dependent on the lowered vitality and power of resistance of the inflamed tissues, and of the white cells of their circulating blood. Healthy parts can successfully resist them, though they are constantly present in surrounding air and on objects, but in this as in all other cases, of bacterial infection, so soon as the tissue is injured, inflamed and lowered in its power of vital resistance, the pyogenic bacteria assail it successfully. Hence, too, the more abundant exudations of lymph, the centres of which are farthest removed from the healthy tissues and from nourishment, are the most prone to suppuration. That the germs can make their way to such deep-seated exudations in the substance of solid tissues is to be accounted for by their gradual advance through the inflamed and weakened structures from the adjacent skin or mucous membrane, or in some instances by reason of their presence in small numbers in the blood. It is further noteworthy that those animals in which suppuration does not occur readily are such as have a special power of resistance to some other organic poisons. Thus the hog, which is supposed to be proof against snake-bite, is also, to a large extent, proof against the pus-forming bacteria.

=Pus.= This is a white, or yellowish white, creamy-looking product, composed of a clear, transparent fluid, rendered opaque by numerous floating pus-corpuscles. These pus-corpuscles have the same size as the white globules of the blood (¹⁄₂₅₀₀ to ¹⁄₃₀₀₀ inch) and are peculiar in that each shows within it three or more nuclei, which become visible on the addition of a drop of water or acetic acid. Each of the common embryonal cells found in the inflamed tissue usually contains two nuclei, the indication of the active increase by division into two, but when the supply of nutriment is checked the nuclei continue to divide, while the cells remain unchanged, and thus every cell comes to contain several nuclei in addition to fatty granules, and constitute pus-corpuscles.

When pus is formed in a well-maintained system and tissue, the outer layer of the lymph is developed into a fibrous sac enclosing the liquid pus and constituting an abscess. In an unhealthy system, or when the inflammation depends on some injurious poison, like that of erysipelas, this sac may not be formed, and the pus, burrowing into and between different organs, destroys the connections and substance—diffuse suppuration. When an abscess has formed in soft tissues its investing sac shrinks as it assumes the fibrous character, and the confined pus being incapable of compression, presses the membrane outward on the side in which the surrounding tissues are most loose and least resistant, hence, usually, though not always, in the direction of the skin; the soft tissues become absorbed and removed in the track of the advancing pus; and, finally, the latter reaches a free surface and escapes. Thus, an abscess usually bursts through the skin, but also, at times, through a mucous membrane into the lungs, bowels, etc., or through a serous membrane into chest, abdomen, etc. When an abscess is formed in bone or dense fibrous tissues which press equally on all sides, it may remain imprisoned for months and years after all inflammation has subsided, constituting an indolent or cold abscess. When the imprisoned pus is inclosed by thick fibrous or resistant tissues at all points but one, it will make its way along the narrow passage of yielding tissue, but as the resulting outlet is constricted, long, and tortuous, the contents cannot readily escape through it nor the walls of the abscess contract so as to expel the confined pus, and the latter goes on forming and discharging through the narrow outlet for months or years. This is a fistula or sinus.

=Healing by Adhesion or First Intention=. When a clean-cut wound has the blood staunched and its lips brought together without exposure to the air (or contact with pyogenic germs), they adhere at once and heal without pus or almost any appreciable formation of new tissue. Here the lymph thrown out on the cut surfaces agglutinates them, and the cells, multiplying, form a thin layer of embryonic tissue which gradually develops into a fibrous structure and repairs the breach without any perceptible scar.