Part 43

From this review of the opinions of various authors the conclusion would seem to be justifiable that the period of incubation in typhoid fever is usually between two and three weeks, but that in many cases it does not exceed ten days, and in rare instances has unquestionably been very much less. On the other hand, there are authentic cases on record in which it is said to have reached, or even exceeded, twenty-eight days. Unfortunately, we do not possess any reliable data with which to decide the question whether it is shorter or longer when the poison is imbibed with the ingesta than when it is inhaled. It would seem, however, that there is a difference in the susceptibility of different individuals to the poison of this disease, in many persons a single exposure to the cause being sufficient to induce an attack, while in others the disease is contracted only after repeated exposure.

MORBID ANATOMY.--As a thorough knowledge of the morbid anatomy of typhoid fever is absolutely necessary to a correct understanding of its pathology, it seems to me better to deviate from the order usually observed in systematic treatises and to proceed at once to a description of the former, rather than to defer it, as it is usual to do, until after the symptomatology of the disease has been discussed.

Rigor mortis is generally more marked and more prolonged than after {261} typhus. Emaciation is often extreme in cases in which death has taken place after the third week, especially if they have been attended by much diarrhoea and fever. No traces of the characteristic rose-colored eruption are found after death, no matter how profuse it may have been during life. Sudamina, on the other hand, persist, and discolorations of the dependent portions from settling of blood are always present in the dead body.

The lesions of typhoid fever may be divided into two classes. The first class includes certain changes in the glands of Peyer, the solitary glands of the intestines, the spleen, and other lymphatic structures of the body. These changes, which consist essentially in a medullary infiltration of these glands, will be minutely described presently. They are peculiar to the disease, and are just as characteristic of it as the condition of the lungs and their membranes found in pneumonia and pleurisy are characteristic of those diseases. They are usually most developed in grave cases, but occasionally they are slight and but little marked in cases in which the general symptoms were severe. They therefore cannot be regarded as the sole cause of the latter. It is more probable that they are themselves the results of the local action of the typhoid poison, and bear somewhat of the same relation to typhoid fever that the eruption in small-pox does to that disease. The second class is made up of lesions which are met with not only in this disease, but in other diseases accompanied by high fever, and are therefore unquestionably the result of the general process. They consist essentially of parenchymatous degenerations of various organs and tissues, and are generally more marked in typhoid fever because the pyrexia is not only of high grade, but also of longer duration than in other diseases.

We shall first consider the lesions peculiar to typhoid fever. Among the most important of these are the changes which occur in the agminated and solitary glands of the intestines. These have been usually described as passing through four stages, as follows: (1) the stage of medullary infiltration; (2) the stage of softening or sloughing; (3) the stage of ulceration; (4) the stage of cicatrization. These stages are said to last almost a week, and correspond to certain definite periods of the disease, but it is not uncommon to find in the same intestine glands in two or more of these stages. Indeed, the same gland may sometimes be found ulcerating at one side while cicatrization is going on at the other.

In the first stage the agminated glands are enlarged, each patch preserving its oblong shape, and being flattened on the surface and elevated from half a line to two lines above the surrounding mucous membrane, from which it is separated by an abrupt border, and which it may in a few cases overhang like a fungous growth. The solitary follicles are also swollen, and may vary in size from a hempseed to a split pea. In very severe cases all the glands may be more or less involved, but in mild cases the changes may be limited to three or four of the patches of Peyer, although the solitary glands rarely wholly escape. It is uncommon also for the latter to be alone affected, but a few such cases have been reported. In these the mucous membrane appears to be studded with pustules, and hence Cruveilhier designated this variety as the forme pustuleuse. The mucous membrane covering the affected glands is reddish-green in color, and that in their immediate vicinity is {262} often injected. The changes above described occur early in the disease--Murchison has seen them in two cases in which death took place at the end of the first day--and they are often well marked at the end of the third or fourth day. They are usually limited to the glands in the lower part of the ileum, the agminated glands being often found perfectly healthy four feet above the ileo-cæcal valve. In mild cases, indeed, the lesions may be confined to those nearest to this valve. So, too, the changes in the solitary glands may be confined to the last twelve inches of the smaller intestine, but this is by no means universally the case, for these glands are not only often found enlarged higher up in the small intestine, but also occasionally in the cæcum. The agminated glands are sometimes found enlarged in the bodies of those who have died of measles and of some other diseases, but the degree of enlargement is rarely as great as in typhoid fever, and the further changes presently to be described are never found except in the latter disease.

Under the microscope the medullary infiltration upon which the enlargement of the glands depends is found to be due to proliferation of the cellular elements. In the case of the agminated glands this proliferation may be limited to the follicles or it may extend to the intercellular tissue, and even to the adjacent mucous membrane. In the former case the patches have a reticulated aspect; they are soft and but little elevated. These are the plaques molles of Louis and the plaques reticulées of Chomel. In the latter they are harder, smoother, and more elevated. To this variety Louis has given the name of plaques dures, Chomel that of plaques gauffrées. The morbid process is also very apt to extend from the solitary follicles to the surrounding mucous membrane.

In a large number of the glands in many cases, and probably in all of them in the abortive form of the disease, the changes never advance beyond the first stage, a restoration to their normal condition taking place by colliquative softening. The morbid material upon which their enlargement depends breaks down into an oily débris which is gradually absorbed. This retrograde process takes place faster in the follicles than in the interfollicular tissue, and, as pigment is very apt to be deposited in the depressions thus formed, the patches acquire an appearance which has been compared to that of a recently shaven beard. This appearance is met with, however, in other diseases, and is therefore not peculiar to typhoid fever.

The description of the changes in these glands in the subsequent stages of the disease which follows is taken mainly from Rindfleisch's work on Pathological Histology.

In the stage of necrosis small portions of single Peyerian patches, varying in size from that of a lentil to from three-quarters of an inch to an inch and a quarter in diameter, assume a yellowish-white, opaque tint instead of their former reddish and translucent aspect, gradually become separated from the surrounding tissue by a sharp line of demarcation, and then pass into a state of cheesy necrosis. Here and there the same changes are observed to have taken place in the solitary glands. When once this has occurred, recovery can only take place by expulsion of the necrosed parts and consequent ulceration. Necrosis of the glands {263} probably rarely occurs before the beginning of the second week, but it has occasionally been observed much earlier. Murchison reports cases in which he saw it as early as the first and second days. The process usually involves the mucous membrane only, but it may extend to the muscular and even to the peritoneal coats.

In the third stage the dead parts are gradually thrown off, the process of separation usually occupying several days. At first an increased degree of congestion, followed by suppuration, is observed at the edges of the sloughs, which before their complete detachment may often acquire a yellow, green, or brown color from the imbibition of bile. The ulcers which result correspond in size and form with the sloughs. They are, therefore, in the case of the agminated glands elliptical in shape, with their long diameter corresponding to the axis of the intestine. Their edges are swollen and overhanging, and their floor is generally formed by the deepest layer of the submucous connective tissue. They sometimes penetrate much more deeply, and may even extend to the peritoneal coat, and thus give rise to perforation of the bowel. The ulcers which result from sloughing of the solitary glands are, as a rule, small and round. Murchison says that ulceration may also be produced in the following way: The mucous membrane becomes softened, and one or more superficial abrasions appear on the surface of the diseased patch, which extend and unite into one large ulcer, and this ulcer proceeds to various depths through the coats of the bowel, and even to completed perforation, but Rindfleisch and other recent German writers do not allude to this process.

The fourth stage, or that of cicatrization, usually commences with the beginning of the fourth week. The swelling of the edges of the ulcers gradually diminishes, and they become adherent to the tissues beneath. The floor of the ulcers covers itself with delicate granulations, which in course of time are converted into connective tissue. This is ultimately coated with epithelium, but neither the villi nor the glands of the mucous membrane are ever reproduced. The resulting cicatrices may be recognized by the affected parts of the bowel being thin and more translucent than in health, and may retain these characters after the lapse of several years. They never give rise to contraction of the bowel. The time occupied in the cicatrization of each ulcer is said to be about two weeks. It occasionally happens that while cicatrization is taking place at one end of the ulcer the process of necrosis and ulceration is still going on at the other, so that two or more ulcers may occasionally run together. This form of ulcer may often retard recovery, and may sometimes end in perforation of the bowel, even after convalescence seems to have been established.

The color and consistence of the mucous membrane of the cæcum and colon are in a large proportion of cases normal. In a few the membrane is paler than in health, and in others it is of an ash-gray color. It is also sometimes injected and softened. The solitary glands are frequently enlarged and ulcerated, like those of the ileum. In the former case the mucous membranes of the large intestine throughout its whole extent, but especially that of the cæcum and of the part of the colon adjacent to it, is studded with minute elevations about a line in diameter. When ulceration has occurred the ulcers are generally round {264} and small, but they may occasionally be oval and of considerable size. In the latter case their long diameter will correspond in direction with that of the circular fibres of the intestine. Murchison has known them to measure fully an inch and a half in length. The colon is generally found much distended with flatus.

Enlargement of the mesenteric glands from cellular hyperplasia and hypertrophy of the connective tissue is constantly associated with the morbid changes of the intestines just described. This enlargement varies in different cases. In some the glands are not larger than a pea or bean; in others they are said to have reached the size of a hen's egg. It is always more marked in the glands which lie in the angle between the lower end of the ileum and the cæcum, and usually bears some proportion to the intensity of the local disease; but it is not to be regarded merely as a result of the local irritation, as it has been observed in parts of the mesentery corresponding to perfectly healthy portions of the intestine, and as the meso-colic glands have been involved in cases in which the colon was free from disease. It has, moreover, been observed in cases in which death has occurred very early in the disease, and there can therefore be little doubt that it is as much the result of the infective process as the infiltration of Peyer's patches. In addition to being enlarged, if death has taken place before the end of the second week the glands are hyperæmic and of a purplish color. Later than this, when the sloughs become detached from Peyer's patches, the swelling of the glands diminishes; they lose their color and become pale, and if convalescence ensues they return finally to their former healthy condition. Still, Murchison has seen them shrivelled and pale or bluish for some time after convalescence. In other cases the substance of the glands softens, with the formation of a puriform liquid. If the softening only involves a small part of the glandular structure, restoration to health may take place through the absorption of this liquid. If it is more extensive, the whole of the glands may break down into this puriform liquid, which, when the patient recovers, undergoes caseous and finally calcareous degeneration. Occasionally, a gland in this condition is the cause of death from rupture and extravasation of its contents into the cavity of the peritoneum.

The glands in the fissure of the liver, the gastric, lumbar, inguinal glands, and indeed all the lymphatic glands in the body, have occasionally been found swollen and congested, but their enlargement cannot be classed among the specific lesions of the disease, but is merely the result of a local irritation. Thus, Jenner says that in the case of extensive ulceration of the oesophagus which came under his observation there was marked enlargement of the oesophageal glands. Liebermeister says that the lymphatic follicles which surround the glands at the root of the tongue and in the tonsils are often affected in the same way as the glands. In most cases after a time the swelling disappears, but sometimes softening and rupture take place.

The spleen is almost invariably found to be increased in volume and to have undergone changes in consistence and color. The degree of enlargement and the other changes vary of course with the stage of the disease at which death has occurred. The enlargement occurs with less frequency in elderly than in young people, and is most marked at the height {265} of the disease, the organ being then often twice or three times its normal size, and in some cases, it is said, even larger. Later, and especially during convalescence, the enlargement has generally very much diminished. During the first ten days of the disease the spleen is generally tense and firm, engorged with blood, and dark red in color. Between the tenth and thirtieth days its appearance remains the same, but the organ is found to be soft and friable. During convalescence it becomes paler and firmer again, and is often so shrunken in size that its capsule is relaxed and wrinkled. Hemorrhagic infarctions are often met with. These sometimes soften and break down into a puriform liquid, which may sometimes cause peritonitis by rupture into the peritoneal cavity. Rupture of the spleen is also said to have occurred from mechanical violence. These changes are due in part to variations in the amount of blood, and in part to a medullary infiltration of Malpighian corpuscles similar to that which takes place in Peyer's patches and the glands of the mesentery.

LESIONS WHICH ARE NOT PECULIAR TO TYPHOID FEVER, BUT ARE OF MORE OR LESS FREQUENT OCCURRENCE.--The mucous membrane of the pharynx and oesophagus may present a perfectly healthy appearance, but occasionally it is congested and the seat of ulcerations which are for the most part superficial. Sometimes, however, they have been found to extend to the muscular coat, but they have never been known to penetrate all the coats of these organs. Jenner refers to one case in which there was extensive ulceration of the oesophagus, but usually the number of ulcers is not large. In a few cases the mucous membrane of the pharynx is coated with diphtheritic false membrane, and the submucous tissue is infiltrated with serum and pus (Murchison).

The stomach and the upper part of the intestinal tract present no lesions which are at all peculiar to typhoid fever. In a certain number of cases congestion, softening, and even superficial ulceration, of the mucous membrane of the stomach, and less frequently of that of the duodenum, have been found. The mucous membrane of the jejunum and of the upper part of the ileum is not usually much reddened, and may be even paler than in health. In cases which have been protracted it may be of an ashy-gray or slate color. The contents of this part of the intestinal tract, which is rarely much distended by flatus, do not differ materially in appearance or consistence from the matter which generally composes the typhoid stool. The bowels may, of course, be found filled with blood in cases in which a recent hemorrhage has taken place. Invaginations of the small intestines, unaccompanied by any evidences of inflammation, are occasionally met with in the bodies of those who have died of typhoid fever. They are produced, there is good reason to believe, during the death agony, but are not peculiar to this disease, as they occur in many other diseases.

Enlargement of the liver has been found in only a few cases after death from typhoid fever. Softening is more common, but even this is not a frequent result of the disease, for it was absent in 41 out of 73 cases examined with special reference to this point by Louis, Jenner, and Murchison. The organ is occasionally hyperæmic, and darker in color than in health, but it is oftener pale or normal in appearance. Even, however, where it appears to be perfectly healthy to the unassisted eye, {266} the microscope shows that its cells are very granular and filled with oil-globules which often render the nucleus indistinct or completely conceal it. When death has taken place at an advanced stage of the disease many of the cells are found to be completely broken down into a granular detritus. These changes are usually proportional to the degree of pyrexia which has been present during life. Rarer lesions of the liver are pyæmic deposits, embolism, abscess, and emphysema.

The mucous membrane of the gall-bladder has been found to be the seat of ulcers by Jenner and numerous other observers. It also occasionally presents the evidences of catarrhal or diphtheritic inflammation. The gall-bladder usually contains a pale watery liquid of a less density than bile. When, however, inflammation of its lining membrane has existed, its contents are mixed with pus and shreds of false membrane.

The mucous membrane of the larynx is sometimes found to have been the seat of catarrhal or diphtheritic inflammation, and sometimes also of ulceration. Jenner says that in typhoid fever laryngitis independent of pharyngitis is extremely rare, but the German writers express a different opinion. Griesinger estimated that laryngeal ulcers were present in one-fifth of the fatal cases. Hoffmann found them twenty-eight times in two hundred and fifty autopsies, and that the ulcers had extended to and involved the cartilages in twenty-two out of the twenty-eight cases. They are most commonly found in the posterior wall of the larynx, and may involve the vocal cords. These are often discovered after death in cases in which their existence was not suspected during life. They were formerly supposed to be the result of typhoid infiltration of the laryngeal glands, but careful investigation has shown that they are the consequence of diphtheritic inflammation of the mucous membranes. Inflammation and ulceration of the trachea are comparatively rare. Hypostatic congestion and infarction of the lungs are not uncommonly found after death from typhoid fever, and less frequently the lesions of pneumonia. Evidences of recent pleurisy are also discovered in a few cases. Acute miliary tuberculosis of the lungs is more often met with as a sequela than as a complication.

The changes in the brain and its membranes caused by typhoid fever are few and unimportant, even in cases attended by severe nervous symptoms. Those most frequently found are adhesions of the dura mater to the inner surface of the cranium, injection or oedema of the pia mater, congestive oedema, and sometimes softening of the brain and effusion at the base of the brain. The microscopic changes do not appear to have been carefully studied. Liebermeister says that the gray substance of the cortical portion of the brain and of the interior is sometimes of a rather yellowish-brown color, and that he noticed besides diffuse yellow and blackish-brown spots in different places, particularly in the corpus striatum and thalamus opticus. In such places, he says, the microscope shows a diffuse yellow coloration, a deposit of small brown pigment-granules, and also, especially in the optic thalamus and corpus striatum, the ganglion-cells thickly crowded with brownish or blackish pigment-granules in such numbers as to conceal the outlines of many of the cells. These changes Hoffmann, who has specially studied them, is inclined to place by the side of the parenchymatous degeneration of other organs. {267} The ganglion-cells of the sympathetic ganglia are said by Virchow also to contain an unusual amount of pigment.

The muscles are frequently the seat of marked changes in typhoid fever. Their macroscopic appearances vary with the stage of the disease at which they are examined. When death takes place in the first or second week they are usually dark red or reddish-brown in color, and very dry. If it is delayed until later, they "present a peculiar fawn or yellow tint permeating the ordinary red in patches and veins not unlike the appearance of veined marble." Their consistence is also so much diminished that the finger may be readily passed through them. Occasionally, pseudo-abscesses and hemorrhages into the muscular sheath are found, and Dauvé and B. Ball report cases in which, in addition to these changes, rupture of muscles had occurred. Zenker, who was the first to call attention to them, ranged the changes seen under the microscope under two heads: (1) granular or fatty degeneration; (2) waxy degeneration. In the first variety the transverse striæ disappear and the sarcolemma appears filled with finely granular matter. In the second variety the striated muscles become, as it were, pervaded by a coagulating material which sets, and in contracting breaks up the fibres into great numbers of short waxy-looking lumps, not unlike a certain variety of casts of the tubuli recti of the kidneys. When recovery takes place the affected fibre is believed to be regenerated by a cell-growth within the sarcolemma. These changes occur in most fevers, as typhus, small-pox, scarlet fever, and are attributed by authors generally to the hyperpyrexia which is a frequent accompaniment of these diseases. Hayem, however, asserts that he has found them well marked in cases not characterized by a high temperature, and that, on the other hand, they are sometimes absent in cases where this has been present. The waxy form of degeneration may affect all the striped muscles, but is oftenest seen in the muscles of the abdominal walls, the adductors of the thigh, the muscles of the diaphragm, and tongue.

The heart, in common with the other muscles of the body, suffers from both the forms of degeneration above described, but the granular form appears to be more common than the waxy. In protracted cases it is usually much softened, and when thrown upon a plate no longer retains its form. It has usually lost its normal color and acquired the tint described by the French as feuille morte (faded leaf). Upon minute examination the degeneration is found to have taken place in patches, the diseased fibres being found alongside of others which have scarcely undergone any alteration. These patches are especially common in the papillary muscles of the mitral valve--a fact which explains the occasional presence of systolic murmurs in typhoid fever. In addition to the microscopic appearances of the muscles already described, Hayem has observed in his examinations of the heart a cellular infiltration of the connective tissue and a proliferation of the muscle nuclei. These changes are sufficient in his opinion to establish the existence of myocarditis. The same observer thinks he has also found evidences of the frequent occurrence of endoarteritis in the multiplication of the cellular elements {268} of the internal coat of the small arteries, which he has discovered under the microscope.

Some discrepancy of opinion exists in regard to the condition of the blood in typhoid fever. Trousseau, for instance, speaks of it as being profoundly altered and in a state of dissolution; Liebermeister says that at the height of the disease the blood is very dark-colored, and that after coagulation it presents a small and soft clot; and Murchison, that a dark, liquid condition of the blood is rarer than in typhus, and that fine white coagula are more common. Harley too has frequently found firm colorless clots of fibrin in the heart and roots of the great vessels in subjects dead in the third week of the disease. Forget concludes from an examination "of one hundred and twenty-three specimens of blood derived from patients in all stages of the disease that an appreciable alteration of the blood in the several periods of enteric fever cannot be accepted as a general fact; that the blood is rarely altered in the first period; that the alteration is more marked in proportion as the disease is more advanced; that the alteration is not always in proportion to the gravity of the disease." I have myself seen the disorganization of the blood as complete in severe cases of typhoid fever which have rapidly proved fatal as in cases of diphtheria or of other malignant diseases. On the other hand, in protracted cases and during convalescence the blood is often thin and watery.

The kidneys are sometimes engorged with blood, sometimes pale and flabby. Under the microscope the appearances are similar to those just described as occurring in the liver, and it is therefore unnecessary to refer to them more fully here. As a rule, the epithelium becomes granular earlier and to a marked degree in the cortical than in the tubular portion. The absence of albuminuria must not always be accepted as proof of a healthy condition of the kidneys, as this symptom has been wholly wanting in cases in which the organs have been extensively diseased.

Analogous changes have also been observed in the salivary glands and pancreas, except that, according to Hoffmann, a cellular proliferation precedes the degenerative process.

CLINICAL DESCRIPTION.--The invasion of the disease is usually so gradual that it is often impossible to obtain from patients exact information as to the time of the beginning of their illness. Among those who present themselves for treatment at the Pennsylvania Hospital it is not uncommon to find that many have suffered for several days, it may be as long as a week, or even longer, before taking to their beds, from vague feelings of discomfort, from headache more or less intense, aching pains in the back or limbs, or from sensations of chilliness alternating with flashes of heat. In other cases derangements of the digestive system are more prominent, such as nausea, or even vomiting, diarrhoea, or irritability of the bowels. Notwithstanding these symptoms, and the indisposition to exertion engendered by them, they have frequently continued to follow their usual avocations up to the time of their application at the hospital for admission. There is generally, however, no difficulty in recognizing at once the nature of their disease. Upon examination the pulse is found to be frequent, the respiration accelerated, the tongue furred, the skin hot and dry, and the abdomen tympanitic.