INFLAMMATION AND ITS SEQUELS. The protean character of inflammation is sufficient explanation of the fact that none of the numerous attempts to define the condition has been entirely successful. The term represents the sum of changes loc ally produced in a living tissue by the action of an irritant, and since the constituents of the tissues and the characters of irritants vary within enormously wide limits, it follows that the phenom ena of inflammation vary within wide limits also. Nevertheless, the four "cardinal signs" indicated by Celsus (A.D. 34) viz., redness, swelling, heat, pain, are in varying degrees present in every case of inflammation, and subsequent centuries only added to these four signs, a fifth, impairment of function.
From a clinical point of view inflammation may be acute, sub acute or chronic, may be widespread or localized, may produce intense destructive changes or little obvious effect, may be rela tively unimportant so far as life is concerned, or may endanger life from the outset. Essentially, however, the phenomena are the same in kind though individually varying in degree to an infinite extent. This is true even if the irritant evoking the inflam mation be one and the same. The micro-organism known as sta phylococcus aureus, lodged in the cardiac valves, produces valvular disease of the heart, with the entire chain of events that valvular disease entails; in the subcutaneous tissues, leads to a pustule; in the liver, to an abscess ; within the skull, to cerebral abscess or meningitis, in the superficial layers of the skin, to a pustular der matitis, to mention but a few examples. Here the different effects depend, in large measure, upon the seat of lodgement of the micro-organisms. Other variations depend upon the specific character of the infecting micro-organism. Lesions produced by B. tuberculosis, Treponema pallidum (syphilis), B. diphtheriae, B. perfringens (gas-gangrene), B. pestis (plague), V. cholerae asiatica, have peculiar characters, so that a cursory examination might fail to discover that essential identity of phenomena which underlies all of them.
The peripheral appearances described above do not occur at the moment that the hot needle is applied, but take some time for their production, and disappear in reverse order until the normal condition of the skin is re-established. That is to say, the local inflammation is followed by regeneration and repair. It is this essential association of reparative or stimulative processes with destructive or inflammatory processes that renders study of inflammation so difficult, but the two types of process must be entirely distinct, for stimulation occurs in the normal processes of life in which inflammation is completely absent, though these same stimulative processes are responsible for the regeneration and repair that normally follow inflammation. In a word, in flammation is essentially degenerative and destructive, but of necessity brings regeneration and repair in its train. Recognition of this principle is of fundamental importance in treatment, as it indicates that before repair can take place at a given spot every source of irritation, i.e., of inflammation, must be removed. It is intelligible, too, that a tissue on the way to repair may itself fall under irritant action. Then the phenomena of repair and of inflammation are commingled ; the result is chronic inflammation.
The phenomena associated with inflammation may be distress ing to the patient, but of temporary importance; on the other hand, they may be so excessive that they constitute in themselves sources of irritation to the tissues in which they occur. A blow in the neighbourhood of the knee may lead to local inflammation, with so much pain and effusion that the joint is kept immobile sufficiently long for atrophy, from disuse, to occur in the muscles moving the joint, and occurrence of adhesions within the joint itself. Hence the primary irritant may be reinforced by secondary and subordinate irritants, and in many instances the latter lead to the greater degree of disability. Other examples of the dom inating influence of these secondary irritants are seen in cases of pleural and pericardial adhesions, ascetic collections of fluid, necrosed bone (sequestra), renal and biliary calculi. In all in stances, however, whether it be by way of primary or of sub ordinate irritants, the tissue elements involved determine the ultimate effects of the inflammation. According as they are nervous, muscular, renal, connective tissue, or of other kind, the features of the symptoms resulting from the inflammatory lesion are determined, and in proportion as the tissue cells themselves are relatively vulnerable and predominate in the affected region, the symptoms are produced by relatively low degrees of irrita tion. Particles of dust that are without effect on the skin or mucous membrane of the mouth may cause profound inflamma tion of the eye; oil of turpentine which, acting on the skin, merely reddens it, when acting on the secreting cells of the kidney, leads to an intense, possibly a fatal, nephritis.
But there is another, and in most respects, a far more impor tant variety of irritant that leads to inflammation. The irritant here is living or organized, and the group embraces the whole range of pathogenetic bacteria and animal parasites that affect the solid tissues. The inflammatory phenomena are dominated by the fact that the irritant has the power of living and multiplying within the animal tissues, and though, fundamentally, the tissue reactions towards this type of irritant are identical with those towards non-organized irritants, the scales are weighted from the first in favour of the irritant and against the tissue it invades. To produce a given result a smaller initial injury is sufficient when the irritant is bacterial, because the irritant has in the toxin it produces a weapon that the non-organized irritant has not, has in its power of multiplication a power of escaping from the region where the tissues are opposing it and carrying its injurious action to a distance. And in the course of these activities it occasions such pathological conditions as abscess, ulceration, gangrene, necrosis, sepsis, fever, nervous symptoms; and the train of ill effects extends indefinitely. Whether the patient succeeds in over coming the primary and secondary irritants, and in repairing the damage they have caused, or succumbs under the attack, is determined by the factors influencing his immunity or suscepti bility.
Here the danger must be indicated of considering inflammation as Merely a local proret"s, one at times affecting a large: area. (;ranted that the local phenomena. attract most attentiorn yet it is clear that the increased local blood flew can only carried out by a re-arrangement of the e:ires,il.ation over the v body, that the exuded fluid implies a general re-arrasigtrr. = - • '. the intro- and extra-vase: War relations, that the localized of leue.,ucytes, often in huge numbers, a redistribution of their numbers within) the care ulatin,g blood, and of ten an inc teased out at t he seats; of t}:= - normal production. The experimental evils - (Jr the zt ssits lies in the altered specific gravity blood and of tissues at distant parts of the body, arid the altered corpubc. ular ((institution of the blood (particularly concerning the n u rr, be'J r,1 !J(Jlysudcear lforncytet) that accompany local inflam mation. iron. _) too, fever, general discomfort, disordered digestion, altered tor: : vtitirm (A the urine are often other indications that the entir=- )',r)y shares in the change,, finally, the production of pe anti-substance?, to antagonize bacterial irritants is a f un= t J',' of the tissues (see bA( J1 k3A AND and J;uch ant . `; .,t.a iced a r = ' ')n veyed by the blood to the region where they t r. • • [ , at the focus of inflammation.
In the case of nerves, the term regeneration is of ten used, but the return of function which may be observed after the severed ends of a nerve have been sutured, is not regeneration in the strict sense. In all the instances described above, regeneration of tissue depends upon re-formation of cells by division of pre-existing cells, but nerve cells once destroyed are never re-formed, and the return of function depends merely upon centrifugal growth of the axis cylinder from the still intact nerve cell along the scaffolding provided by the anatomical nerve, whose continuity has been restored by suture. Experiments that have been regarded by their authors as indicating that the functional nerve is restored by longitudinal apposition of proliferated neuroglial cells, do not carry conviction.
(I) An Aseptic Surgical W ound.—The irritant here is the knife, and subordinate irritants are reduced to a minimum, probably being represented by the stitches, a small number of tissue cells on the cut surfaces that are injured beyond recovery, and small amounts of blood clot. As the result of these local dilatation of vessels occurs, exudation is poured out in the superficial layers of the opposed cut surfaces, and between them and by coagula tion, temporarily binds them together. Polynuclear leucocytes migrate from the blood stream and by phagocytosis (q.v.) remove dead tissue and remnants of blood clot, and later the fibrin fila ments of the coagulum. At the same time newly-formed capil laries bridge the gap between the two cut surfaces, travelling along the fibrin filaments in the intervening coagulum. Fibroblasts, derived from pre-existing connective tissue corpuscles, range them selves along the new capillaries and build up fibrous tissue whereby the two opposed surfaces are definitely united. On the surface, squamous epithelial cells divide and fill the skin defect and healing is complete. As the newly-formed fibrous tissue grows older it contracts and obliterates the majority of the newly-formed capil laries, so that the scar tissue, which at first was red and excessive, becomes dead-white and contracted.
(2) Fracture of a Long Bone.—(a) the fracture is simple and aseptic. Here the irritant is the force that leads to the fracture, and subordinate irritants, consisting of effused blood from rup tured blood-vessels, torn muscles and ligaments, ruptured medulla of bone, play an important part in respect of their volume, while movement between the fractured ends of the bone may further enhance these. Nevertheless, coagulation of the effused blood oc curs about the ends of the bones and holds them together as a preliminary. The essential difference between the processes here and those obtaining in an aseptic surgical wound consists in the greater mass of material that has to be removed, the greater space that has to be bridged by newly-formed capillaries, the greater distance the migrated polynuclear cells have to travel, and the fact that the endosteum and periosteum, with their osteogenetic cells, are involved instead of white fibrous tissue. In time the blood coagulum around, between and within the fractured ends of the bones, is replaced by a mass of soft bone (temporary callus) derived from periosteum and endosteum, and of this the greater portion is ultimately removed by osteoclastic (i.e., phagocytic) action, while between the fractured ends there remains newly f ormed bone that becomes denser and unites the fracture (defini tive callus). Where the fractured ends are widely separated bony new formation may be impossible and the ends are united, if at all, by fibrous tissue: (b) the fracture is compound and septic. Here the irritant action is increased by the presence of pathogene tic bacteria and their toxins in damaged, dying and dead material resulting from the fracture itself. The pathological sequels of in flammation, suppuration and necrosis, are therefore superposed upon the already important secondary irritants occasioned by the fracture. Even assuming that the bacterial infection does not become generalized and lead to septicaemia or pyaemia (see SEPsis) the original amount of damage to tissues will be in creased by that amount, which is due to the bacterial action as such. When and if these potent adjuvants of the original irritant action have been overcome, and only at those spots at which this occurs, do strictly reparative processes take place, but they are identical with those occurring in an aseptic fracture. In other words, the first object of the body is to render the condition aseptic, and this object the surgeon copies in his treatment of every compound fracture. It can be understood that whereas the healing of an aseptic surgical wound with surfaces well apposed is a matter of days, the healing of a simple, aseptic fracture of bone is a matter of weeks, and the healing of a compound, septic frac ture is one of months.
(3) A Focus of Pulmonary Tuberculosis.—Here the primary irritant is B. tuberculosis, and an apparent difference from the processes summarized above lies in the facts that the reaction of the lung tissue to the bacillus is cellular only, and contains so called giant cells, and that blood vessels are absent from the minute nodule or tubercle. The caseation so characteristic of tuberculosis is dependent upon these differences (see TvBERCU which are correlated with the relative chronicity of the process. But the tubercle when formed, besides replacing a certain amount of lung tissue, is a foreign body, and as such leads to in flammation in the surrounding tissues, often with a degree of con gestion that explains the haemoptysis that may accompany early tuberculosis. If it be situated on the surface of the lung the tubercle induces inflammation of the pleura, local death of endothelial cells, and subsequently the production of fibrous tissue in the form of a pleural adhesion. Within the lung itself the tubercle, after undergoing caseation and, perhaps, calcifica tion, becomes surrounded by fibrous tissue in the same way, and by the same local proliferation of fibroblasts, that a fibrous capsule is formed around an aseptic bullet lodged in the tissues. Should the tubercles be numerous and uncomplicated the result ing fibrosis may be irregular and extensive, and should the lesion be complicated by access of pyogenetic micro-organisms, suppu ration and the formation of a phthisical abscess cavity (vomica) are super-added. But even in the latter case, if the primary and subordinate irritants be overcome, the defect of lung is repaired by newly-formed fibrous tissue, which is as surely scar tissue as in any of the other instances that have been adduced.
(4) An Abscess and an Ulcer.—These two conditions are bracketed because an ulcer may be regarded as an abscess from which part of the wall restraining the pus is wanting. Hence the pus produced on the floor of an ulcer drains away as it is formed, whereas in the abscess it accumulates within the abscess cavity. Microscopically, however, the floor of an ulcer and the wall of an abscess are composed of the same elements arranged in the same fashion. When the bacterial irritant has become lodged within a tissue, and has multiplied sufficiently and produced enough toxin to destroy the neighbouring tissue cells, by the or dinary processes of inflammation it produces a hard, hot, painful swelling which consists of coagulated exudation, numbers of poly nuclear leucocytes, dead tissue cells, and living and dead bacteria, the central part becoming liquefied later by proteolytic action and constituting the pus. This focus of inflammation is sur rounded, as has been said earlier, by a zone in which the irritant action has fallen off in intensity to a level at which it ceases to be an irritant and becomes a stimulus. At some less or greater distance from the focus of inflammation, therefore, the necessary factors for the formation of new capillary blood vessels, the pro liferation of connective tissue cells and the production of young fibrous tissue, i.e., the formation of granulation tissue, are present. Obeying hydrostatic laws, the pus within the abscess "points," and by destruction of superficial layers of tissue, ultimately escapes. Relieved of this subordinate source of irritation the wall of the abscess contracts, and the reparative fibrous tissue con stituting the wall goes on to the formation of definite scar tissue instead of breaking down to swell the contents of the abscess. It is at this stage that the abscess and ulcer are identical in com position. In both instances the most superficial layers of the granulation tissue break down into pus, which drains away, and the final healing only takes place when the surrounding epithelium (or in the case of an abscess in an internal organ covered by serous membrane, the endothelium) has regenerated a covering for the newly-formed scar tissue, and has thereby eliminated the possibility of bacterial irritant action.
By application of the principles outlined above a rational ex planation of most examples of inflammation and the phenomena associated therewith can be obtained. Naturally, factors arise that are difficult, even impossible in our present state of knowledge, to explain. One of these is the relation of irritative to stimulative action. According to some authorities, the repair that follows in flammation is initiated by hormones produced by the injured tissues. They see in the formative processes following inflamma tion something akin to the processes which, under other conditions, lead to the production of neoplastic tumours. (W. S. L.-B.)