The lymph-nodes near the local manifestations arc always affected, and even the remote lymph-nodes, though in a lesser degree. They are swollen and, in severe cases, inflamed; in gangrenous processes oedem atous infiltration also occurs in the periglandular connective tissue.
Sooner or later, following these changes there develop more or less severe general symptoms, which can only.be attributed to the absorp tion into the circulation of the toxins formed at the site of invasion, for the diphtheria bacilli, because of their demand for oxygen, multiply only on the superficial layers of the mucosa, especially of the respira tory tract (preference for cylindrical epithelium), hardly ever pene trating into the fluids and internal organs; when this exceptionally occurs, they very quickly die out. A febrile disturbance follows, and symptoms of degeneration appear, affecting especially the heart, the parenchymatous organs and the peripheral nerves.
The clinical picture produced by the diphtheria bacilli and the germs ordinarily aiding them, shows certain fundamental differences: (1) according to the location of the invading germs; (2) according to the behavior of the attacked niucosa toward the invasion; and (3) ac cording to the quantity and quality of the toxin, on the one hand, and on the susceptibility of the patient, on the other.
The onset and course of the disease may be violent or gradual, and sometimes the local, in others, the general. symptoms predominate.
The mucous membrane reacts to the bacillary irritation often with only slight superficial inflammatory products, in other cases with a penetrating inflammation and profuse fibrinous exudation. This may happen in the same individual, the mucosa in different places showing a varying reaction to the same infection.
The general symptoms of toxasmia, may be limited to a moderate fever of brief duration with a transient. albuminuria, or it may comprise severest disturbances of the general well-being, with marked albumin uria, affection of the myocardium and paralyses. Local and general predisposition usually go parallel to each other, but this is by no means always the case (Escherich). Thus, severe tox{emia may accompany very slight local deposits, and, on the other hand. the general condition may be practically undisturbed with extensive membrane-formation.
The local process, as well as the general intoxication, can bring about a fatal termination. The local process does so when it is situated in the air-passages, with an inflammation of such high degree that the swelling of the soft parts and the pseudomembranous formation prevent the entrance of air. The general toxalnia results in death when it causes irreparable injury to the vital organs, especially the heart. Finally, death may he caused by infection.
Natural recovery follows the action of non-specific protective bodies, already present, the alexins of the blood, as well as the specific reaction of the organism by which the effect of the diphtheria toxin is in part neutral ized. The loosening of the pseudomembrane appears to be brought
about in a special way by the entrance of staphylococci into the meshes of the fibrin-network, through which they are scattered extensively. Their metabolic products, in a chemotactic way, bring out great num bers of leucocytes to act as phagocytes; these, by their death, favor the destruction and removal of the membrane. Then the fibrin turned to pus or fat is thrown off and expectorated. In the larynx and trachea the deposit is more quickly removed because it is lifted up by the in creased secretion of the mucous glands of the membrana propria, and so is loosened in its whole extent. The healing of the ulceration, left after the false membrane has been shed (rare in the larynx and trachea), is brought about by the proliferation of the intact epithelium in the vicinity, which gradually grows over the gap. Very deep diphtheritic ulcers arc followed by permanent loss of substance with scar-formation (healing only by the activity of the subcpithelial connective tissue).
Mucous Membrane.—The mucous membrane affected by diph theria is swollen, (edematous, strongly injected, often lnemorrhagic, while the pseudomembranes, which vary in extent and in the tenacity with winch they adhere to the underlying tissues, show all variations in color from black to white. They are granular, crumbling and soft, or firm, tough and elastic. On section the thin membranes are merely a cellular fibrinous infiltration of the superficial layer of epithelium. In the thick membranes different layers are seen. At the top is a layer of granular detritus in which are found diphtheria bacilli and the sapro phytes ordinarily present on the mucosa. Below this is a layer of fibrin with very close filaments containing only diphtheria bacilli and remains of the epithelium which can scarcely be recognized. Next comes a net work of fibrin enclosing lcucocytes and more or less altered epithelial cells, the filaments becoming further apart towards the mucosa. In only the superficial layer of epithelium is necrotic, the layer of fibrin with leucocytes sprinkled through it is sharply outlined with its lamellated structure against the stratum proprium. In "diphtheria" the membrane and necrosis extend to the submucosa, fibrin-formation is seen in the follicles of the glands and in the lymph-spaces, in the limit ing connective tissue; in the swollen lymph-nodes of the neighborhood and here and there in the blood vessels. At the boundary of the ne crotic tissue lies a dense wall of leucocytes (see Plates 22 and 23). _ The lymph-nodes are swollen, hyperwmic, hemorrhagic and show diffuse or circumscribed necrosis on section. At times the periglandular tissue is infiltrated. Microscopically there arc not rarely found groups looking like miliary tubercles but without caseation or giant-cells. The blood vessels of the lymph-nodes may be occluded with thrombi.