Chapter XII: Front Matter (12)

PURPURA HÆMORRHAGICA (MORBUS MACULOSUS WERLHOFII).--In this form of purpura there are added to the symptoms of purpura simplex hemorrhages into and from the various mucous tracts, the nasal, faucial, pharyngeal, gastric, intestinal, renal, uterine, rarely the pulmonary mucous membranes, and exceptionally into the various serous membranes and cavities. It may begin abruptly, in the midst of apparently vigorous health, or after premonitory symptoms extending over several days, vague sensations of discomfort--headache, pains, anorexia, indisposition to exertion, and the like--or it may occur as a transition from other forms of purpura. Usually there is no fever.

The hemorrhagic spots upon the skin appear much as in purpura simplex, though the lesions are larger, acquiring the size of coins or even of the palm of the hand. Spots soon appear upon the visible mucous membranes, and free hemorrhages occur; indeed, the latter may be the first symptom observed. Epistaxis is of most common occurrence, but bleeding from the mouth, stomach, and intestines almost as frequently results. The gums are almost constantly affected, and upon inspection these may be found covered with blackish scabs, upon removal of which the mucous membrane will be found pale and not swollen--an important point in diagnosticating this affection from scurvy. Vesicles and blebs filled with blood form both on the skin and mucous membranes. They quickly rupture and discharge their contents. Bleeding from the stomach and intestines is revealed--in the former case by the vomiting of a brownish material resembling coffee-grounds; in the latter case by the passage of black, tar-like evacuations. Pulmonary hemorrhage is to be distinguished from hæmatemesis by the frothy and arterial character of the blood. Hæmaturia may proceed from any part of the urinary tract. Bleeding from several parts may occur at the same time, and may be very copious.

In the mucous membranes extravasations of greater or less extent may occur, as in the derma. Into the serous membranes they may take place with or without effusion into serous cavities. It is only, however, in cases that will almost certainly end fatally that the effusions into these cavities are encountered. Hemorrhages into the substance of the lungs, into the brain and other viscera, as well as into the tissues generally, are occasionally observed.

At the outset of these bleedings the general health of the patient may appear unimpaired, and if they be few in number and moderate in extent but slight evidences of debility may be shown throughout the attack; but it is often the case that the loss of blood is excessive and long continued, and symptoms of profound anæmia supervene. The {189} patient becomes greatly exhausted; intense pallor is developed, shortly followed by general oedema. Attacks of syncope appear, and in fatal cases--which are not common--death results from asthenia. This result may occur after a few days from the profuseness of the hemorrhage; usually, however, only after several weeks. Throughout the attack the cutaneous lesions continue to develop, either irregularly or in successive outbreaks, scattered over the general surface, involving the face less frequently than other parts. These spots undergo the color-changes peculiar to extravasated blood, and may be seen in all the stages of involution in the same patient. Fever, usually absent throughout the attack, may appear at the height of the affection, but does not run high. Local inflammations are exceedingly rare. In favorable cases recovery follows the gradual mitigation and disappearance of the symptoms, but relapses frequently occur, and convalescence may be retarded for months.

PURPURA RHEUMATICA (PELIOSIS RHEUMATICA).--Schoenlein in 1829 described as peliosis rheumatica an affection in which the symptoms of purpura simplex were associated with pain and often with effusion into the joints, especially those of the knee and ankle. He considered it as an independent malady. This opinion has been shared by Fuchs, Hebra, Kaposi, Neumann, and many others. Kaposi[2] regards it as related to erythema nodosum, with which affection, indeed, it possesses some features in common. It probably, however, constitutes a complication of ordinary purpura. That it is not primarily rheumatic is shown by the almost invariable absence of many of the symptoms characteristic of rheumatism; that it cannot be an independent affection appears from its intimate relations with other forms of purpura.

[Footnote 2: _Hautkrankheiten_, 1880, p. 277.]

Purpura rheumatica commonly begins with malaise, anorexia, debility, sometimes with mild fever. The patient is soon attacked with pains, of a more or less acute character, in the joints, especially the knees and ankles. There may be some effusion into the joint and cutaneous oedema. After a few days the nature of the complaint will be revealed by an eruption of petechiæ, first near the painful joints, but soon extending, involving in many cases even the head and trunk. The eruption may be at first slightly elevated and surrounded by a fine halo of hyperæmic injection.

The pains usually subside upon the appearance of the eruption, and the malady may be completed after a single outbreak. More commonly new joint-pains are experienced, fresh crops of petechiæ appear, and the trouble may be prolonged for weeks, even months, the patient meanwhile suffering not very greatly in general health. The lesions may be cutaneous only; rarely bleeding from mucous surfaces will occur (Scheby-Buch). Albuminuria may be present (Kaposi). An annual type is said by Kaposi, Neumann, and others to be sometimes observed, the spring and autumn being the usual seasons for the outbreaks. This is supposed to indicate a relationship with erythema nodosum and multiforme. Cardiac murmurs have been detected in the course of purpura rheumatica,[3] but these were probably anæmic or antedated the purpuric symptoms. Purpura rheumatica never seems to result in endo- or pericarditis.

[Footnote 3: Kinnicutt, _Archives of Dermatology_, i. p. 193; Mollière, _Ann. de Dermatol._, v. p. 44.]

SUB-VARIETIES.--Henoch[4] and Couty[5] have described a form of {190} purpura mostly observed in children, in whom rheumatoid pains occur along with colic and vomiting of greenish or bilious matter, tenesmus, and sometimes with loss of blood from the bowels. The disease may be protracted throughout months by relapses. Cutaneous oedema frequently occurs. Couty regards it as a form whose peculiarities justify its assignment to a position of its own. The cause of the associated train of symptoms is supposed (Couty) to reside in the sympathetic system, and the name purpura nervosa is proposed for it. So many features of ordinary purpura are manifested in these cases that it seems better to consider them as examples of ordinary purpura complicated with gastro-intestinal derangement. It has been suggested that the nausea, vomiting, and abdominal pains may result from extravasation of blood into the peritoneal tissue.[6]

[Footnote 4: _Berl. Klin. Wochenschr._, 51, 1874.]

[Footnote 5: _Gaz. Hebd._, 36 _et seq._, 1876.]

[Footnote 6: Immermann, _Ziemssen's Cyclopæd._, vol. xvii. p. 265.]

In the course of purpura there is frequently observed, more especially in purpura simplex, a wheal-like arrangement of the eruption--such, indeed, as occurs in urticaria. The term purpura urticans has been given to this sub-variety, which may or may not be accompanied by itching. Scheby-Buch has suggested that the urticaria may, with more propriety, be attributed to the gastric disturbances that so often accompany the forms of purpura presenting it.[7] The wheals are usually seen upon the lower extremities, but may appear elsewhere. A considerable degree of oedema may be present, particularly in lax tissue, such as that of the scrotum, eyelids, etc.

[Footnote 7: _Deutsche Arch. f. Klin. Med._, B. xiv. p. 490.]

Purpura papulosa (lichen lividus, Willan) is a form of purpura where, in the midst of ecchymoses, livid papules appear. These probably depend upon a large amount of hemorrhage occurring within a limited space, most often surrounding the orifices of hair-follicles, because these are supplied with a capillary network that comes directly from the deeper layer.[8] They are formed most abundantly on the legs of scrofulous, cachectic persons who have purpura. Care must be taken to distinguish this form of purpura from erythema multiforme and erythema nodosum, where blood is usually extravasated secondarily into the tissues. Those cases only where the purpura is primary should be recognized as purpura papulosa.

[Footnote 8: Hebra, _Skin Diseases_, New Syd. Soc. Transact., ii. p. 425.]

The purpuric effusion appears to act as an irritant upon the tissues, and to excite inflammation. Gangrene of the mucous coat of the intestines has resulted from extensive hemorrhagic extravasations, and from a similar cause cutaneous gangrene has been known. These complications, however, are rare.

ETIOLOGY.--The immediate causes of purpura are quite unknown. Both sexes and persons of every age are affected by it. While it is most often seen in debilitated subjects, those in vigorous health possess no immunity. It has often been observed during convalescence from other maladies. It cannot be said that those who are miserably clothed, fed, and lodged are especially predisposed to attacks of purpura. Between purpura and hæmophilia, etiologically, there are many points of difference. Purpura is not hereditary, nor is there a purpuric diathesis in the strict sense of the term. Some persons, indeed, seem to possess a {191} predisposition to the disease, and some authors claim for purpura rheumatica a distinct annual type. This, however, is not at all certain.

Recently it has been claimed that purpura hæmorrhagica depends upon the presence of a minute organism in the blood. Petrone[9] injected blood drawn from patients with this disease under the skin of rabbits, producing widely-distributed hemorrhages. In the blood of these individuals and of the injected rabbits micrococci and bacilli were detected. Watson Cheyne[10] also describes a plugging of the capillaries with bacilli. These were 1/7700 of an inch in length and 1/20000 of an inch in diameter, and were arranged in colonies. In another case there were found micrococci arranged in chains. These swarmed in the capillaries and some larger vessels, and sometimes completely blocked them. Although an origin in infection has thus been claimed for purpura hæmorrhagica, the fact that more than one variety of micro-organism was observed cannot fail to excite suspicion of, possibly, erroneous observation.

[Footnote 9: _Lo Sperimentale_, 51, 1883.]

[Footnote 10: _Lancet_, i., 1884, 344.]

PATHOLOGY.--In the foregoing description those extravasations of blood due to simple mechanical violence, as from flea-bite, and sudden increase of blood-pressure, as in the effort of coughing in whooping cough, also from the deleterious influence exerted upon the blood-vessels and blood by certain drugs, the specific fevers, Bright's disease, and the like, have been excluded. Only those have been considered where the effusion of blood seemed to occur spontaneously, and the symptoms to result from some peculiar but not understood morbid process. The hemorrhage is but a symptom; the process by which it is brought about depends upon some change in the blood or blood-vessels. We do not know what these subtle changes are. The blood of purpuric patients has been carefully examined, but, with the exception above mentioned, no definite changes have been discovered. Immermann[11] found during the first stage of the disease the blood-corpuscles perfectly normal in appearance, the white corpuscles subsequently slightly exceeding the red in number--a simple result of copious hemorrhage. No stated chemical changes in the blood are known in purpura, nor is it known how the blood escapes from the vessels. It undoubtedly escapes through alterations in the vascular wall, but it is also true that red blood-corpuscles, as well as the pale ones, may find their way in considerable numbers through the unruptured wall of the vessels, per diapedesin, as was first suggested by Velpeau, but definitely determined by Stricker. The causes of this migration are obscure. Immermann[12] asserts that a fatty degeneration of the vascular tissues and of the muscles takes place. This, however, is manifestly a result of the loss of blood, and not its cause. Dr. Wilson Fox[13] found extensive albuminoid disease of the muscles and capillaries of the skin; but the albuminoid degeneration involved several organs of a patient with syphilis, and the purpura was certainly secondary to the morbid conditions. Rigal and Cornil[14] think that the hemorrhages are a result either of sympathetic irritation or of diminished action of the vaso-motor centre. It is indeed altogether likely that the cause will ultimately be found to reside in the vaso-motor system.

[Footnote 11: _Ziemssen's Cyclop._, xvii. p. 258.]

[Footnote 12: _Loc. cit._]

[Footnote 13: _Brit. and Foreign Med.-Chir. Review_, Oct., 1865.]

[Footnote 14: _L'Union Méd._, 5, 6, 7, 1880.]

{192} DIAGNOSIS.--The affection bearing the closest resemblance to spontaneous purpura is scurvy; indeed, its supposed relationship to this disease has given purpura one of its synonyms, land scurvy. The two affections, however, are probably without the slightest relationship. They possess in common the hemorrhagic symptoms, both in the tissues and from free surfaces, but the resemblance does not extend much beyond this. Scurvy depends upon deprivation of fresh vegetable food and the use of unsuitable and insufficient food generally, and upon bad hygienic surroundings. Purpura may--frequently does--appear in broken-down constitutions, but it equally attacks the strong and vigorous, while the character of food exerts no special influence on its production. Scurvy only follows long-continued privations and as a culmination of a train of distressing symptoms. Purpura appears in the midst of health, or after brief premonition, or during convalescence from totally unrelated diseases. In scurvy there is a decided tendency toward ulceration, which is absent in purpura. In scurvy the mouth and gums inflame and ulcerate, the latter becoming swollen, spongy, and of a bluish-red color. In purpura, ulceration of the buccal mucous membrane does not occur, and the gums are pale and intact. The curative influence of fresh vegetables, lime-juice, etc. in the treatment of scurvy is not observed in purpura. It has been claimed that purpura is but a mild degree of scurvy: this cannot be so, for we may have a mild scurvy or a severe, even fatal, purpura.

The hemorrhagic diathesis, or hæmophilia, presents points of analogy with purpura. Here, however, is found the almost constant history of heredity and the implication only of persons of the male sex. The disposition to bleed at all times upon the receipt of the smallest injury is quite unlike the suddenly-developed and transitory hemorrhages of purpura, which are also more generally distributed.

With the secondary hemorrhagic effusions and ecchymoses that occur in conditions of profound alterations of the blood and blood-vessels in cases of malignant small-pox, scarlatina, typhus fever, etc., and in some cases of poisoning, as from phosphorus, spontaneous purpura presents identities, but the history of the complaint and the condition of the patient will prevent error. A knowledge of the circumstances will serve to distinguish purpura simplex from the petechiæ and small ecchymoses produced by fleas, by diminished atmospheric pressure, by coughing, in the course of Bright's disease, etc.

Purpura rheumatica presents, as has been shown, many points of resemblance to erythema multiforme and erythema nodosum. The mild fever, the joint-pains, the extravasations of the latter affections, are much like the symptoms of this form of purpura. The nodular, inflamed, tender condition of the lesions, their location--frequently upon the extensor surfaces of the extremities--their course and duration, usually serve to identify erythema nodosum, while with erythema multiforme it is usually not difficult to observe its essentially inflammatory character. Scheby-Buch has shown the difficulties often opposed to the differentiation of purpuric lesions and ecchymoses due to violence.[15] Where the petechial eruption of purpura simplex is well marked, where the internal hemorrhages of purpura hæmorrhagica are copious, the inquiries of the observer will usually lead him to correct conclusions. Where the {193} ecchymoses are larger and upon exposed parts of the body, the diagnosis from the lesions alone becomes impossible, and due consideration of all concomitant circumstances is essential. It should be remembered that in purpura very slight violence may call forth extensive ecchymosis. This circumstance has important medico-legal bearings.

[Footnote 15: _Viertelj. f. Dermatol. und Syph._, 1879, p. 99.]

PROGNOSIS.--Purpura usually terminates favorably. Its course runs from two to six weeks, rarely longer. Relapses and remissions are frequent. Purpura simplex is of very little gravity, and need excite little apprehension. Purpura rheumatica almost always ends in recovery; fatal terminations, however, have been known. Purpura hæmorrhagica is of much more serious import. Even here, however, though the patient may fall into profound debility from loss of blood, recovery is the rule, the symptoms gradually diminishing in severity until health becomes re-established. In fatal cases death ensues after prolonged and profuse losses of blood. Purpura may subside after a single outbreak or many relapses, and recrudescences may occur extending through months. Anæmia may persist long after the disappearance of purpuric symptoms. A tendency to purpura may be shown at irregular intervals for years, and even throughout life.

TREATMENT.--Very mild cases of purpura simplex require no treatment, not even confinement within doors. The patient is often first made aware of his disease by accident; doubtless it frequently escapes detection altogether. It has been observed that purpura often appears upon the lower limbs of convalescents from other diseases when they first essay the upright position. Relapses of purpura also frequently appear as the patient leaves his bed. We have here an important indication for treatment--viz. the maintenance of the recumbent posture in cases of any degree of severity. Fresh vegetables and vegetable acids do not have the same happy influence as in scurvy. It is manifestly important that appropriate food should be administered in sufficient quantity, both to improve the general health and to repair the exhausting losses of blood. Milk is an exceedingly valuable article of diet in these cases, being but little apt to irritate the mucous membrane of the alimentary canal.

The patient should be guarded against violence. Injuries that may be of no consequence to healthy persons may excite in the purpuric profuse hemorrhage, free or interstitial. Violent emotions and physical efforts should be avoided, as in stimulating the heart's action a condition of increased blood-pressure ensues that may readily result in extravasation.

There are no remedies that exert a specific influence over purpura, and yet quite a number have enjoyed, and still enjoy, high reputation in controlling the symptoms. Probably the most frequently employed remedy against purpura is sulphuric acid, preferably the aromatic sulphuric acid, in doses of from 15 to 20 drops, diluted well with water and administered every third or fourth hour. It is certainly an agent of value, though some authors maintain that it has no efficacy (Immermann). Acetate of lead undoubtedly exercises an influence over the course of the disease. More recently, ergot has been employed. Its use has been highly extolled by Buckley and others. Very large doses may be given. The hypodermic use of ergotin has been followed by results most gratifying to those employing it. Oil of turpentine has enjoyed considerable reputation. A remedy that undoubtedly has a good effect is iron, both as {194} exercising a controlling action over the bleeding and as assisting to repair the resulting anæmia. The tincture of the chloride is the most suitable preparation, and may be given in large doses (from minim xx to fluidrachm ss), well diluted, every fourth hour. Care must be exercised to avoid irritating the digestive organs with it. Formerly, venesection was employed to prevent the occurrence of hemorrhage, but its efficacy in this direction is at least doubtful, and cannot but help to intensify the disastrous consequences of severe and protracted attacks.

The various complications that may arise, as well as the general results of purpura, must be treated symptomatically. For the mucous membranes astringent washes should be used, and in favorable situations the tampon may sometimes be employed with profit. In purpura rheumatica the arthritic pains will be alleviated by anodyne liniments and plasters, and the often accompanying abdominal pains and colic by anodynes internally administered. Hæmatemesis, hæmaturia, etc. must be treated upon general principles. The results of profuse hemorrhage must be combated with stimulants. Transfusion of blood has been proposed and practised for the extreme anæmia that sometimes occurs, but without encouraging results. If necessary, the bowels may be kept free by mild aperients. In severe cases rest in bed should be rigidly enforced until after the establishment of convalescence. Quinia, iron, and nux vomica are indicated above all other remedies for the anæmia resulting from an attack of purpura.

{195}

DIABETES MELLITUS.

BY JAMES TYSON, A.M., M.D.

Diabetes mellitus is a term applied to a group of symptoms more or less complex, of which the most conspicuous is an increased flow of saccharine urine--whence the symptomatic title. It is associated with a derangement of the sugar-assimilating office of the liver, as the result of which an abnormally large quantity of glucose is passed into the hepatic vein and thence into the systemic blood, from which it is secreted by the kidneys. The condition is sometimes associated with alterations in the nervous system, at others with changes in the liver or pancreas, while at others, still, it is impossible to discover any structural alterations accompanying it.

PATHOLOGY AND PATHOGENESIS.--Notwithstanding that this disease has been recognized for two centuries and a half, that abundant opportunity has been furnished for its post-mortem investigation, and that experimental physiology has contributed much information bearing upon the subject, its pathology is still undetermined. Experiment has, however, rendered it very likely that all cases of essential glycosuria--that is, all cases in which saccharine urine is not the direct result of over-ingestion of sugar or sugar-producing food--are accompanied by a hyperæmia of the liver. This hyperæmia, with its consequent glycosuria, can be induced by puncturing or irritating the so-called diabetic area[1] in the medulla oblongata. This area corresponds with the vaso-motor centre, and with the roots of the pneumogastric or vagus nerve in the floor of the fourth ventricle; whence it was at first inferred that this nerve is the excitor nerve of glycosuria. It was soon ascertained, however, that when the pneumogastric was cut, glycosuria ensued only when the central end was stimulated, while {196} stimulation of the peripheral portion was without effect. Whence it became evident that this nerve is not the excitor, but the sensory nerve concerned in glycogenesis.

[Footnote 1: The diabetic area, as marked out by Eckhard, and which corresponds with the vaso-motor area, as defined by Owsjannikow (_Ludwig's Arbeiten_, 1871, p. 21), is bounded by a line drawn four or five mm. above the nib of the calamus scriptorius, and another about four mm. higher up.]

It was also learned in the course of continued experiment that glycosuria resulted upon transverse section of the medulla oblongata, of the spinal cord above the second dorsal vertebra, of the filaments of the sympathetic accompanying the vertebral artery, upon destruction or extirpation of the superior cervical ganglion, and sometimes, but not always, after division of the sympathetic in the chest (Pavy); also after section or careful extirpation of the last cervical ganglion, section of the two nerve-filaments passing from the lower cervical to the upper thoracic ganglion around the subclavian artery, forming thus the annulus of Vieussens,[2] and after section or removal of the upper thoracic ganglion.

[Footnote 2: Cyon and Aladoff, reprint from the _Mélanges biolgiques_ and _Bullétin de l'Académie Impériale de Petersbourg_, vol. xiii. p. 91; cited by Dr. Brunton in the Lectures named in note on p. 198; also _British Medical Journal_, Dec. 23, 1871, p. 731.]

_Trach._, trachea; _Ca._, carotid artery; _n. vag._, the vagus trunk; _n. rec._, the recurrent laryngeal; _sym._, the cervical sympathetic nerve ending in the inferior cervical ganglia, _gl. cerv. inf._ Two roots of the ganglion are shown--_rad._, the lower of the two accompanying the vertebral artery, _A. vert._, and being the one generally possessing accelerator properties; _gl. thor. pr._, the first thoracic ganglion. Its two branches, communicating with the cervical ganglion, surround the subclavian artery, forming the annulus of Vieussens. _sym. thor._, the thoracic sympathetic chain; _n. dep._, depressor nerve. This is joined in its course by a branch from the lower cervical ganglion, there being a small ganglion at their junction, from which proceed nerves to form a plexus over the arch of the aorta. It is this branch from the lower cervical ganglion which possesses accelerator properties, hence the course of the accelerator fibre is indicated in the figure by the arrows. (Modified from Foster's _Physiology_.)]

All these operations paralyze the vaso-motor nerves by which, in health, the blood-vessels of the liver are kept in a state of tonic contraction; hence these vessels dilate when the nerves are cut. From the facts named we also learn the path of the glycogenic influence, which must be from the medulla oblongata into the spinal cord, thence by the filaments of the {197} sympathetic which accompany the vertebral artery into the lower cervical ganglion; thence through the annulus of Vieussens into the first dorsal ganglion; and thence through the prevertebral cord of the sympathetic, and branches not precisely determined, to the hepatic blood-vessels as shown by the dotted line in Fig. 3.

I say, by branches of the sympathetic not precisely determined, because our power to produce artificial diabetes fails below the first thoracic ganglion; for section of the sympathetic between the tenth and twelfth ribs, and of the splanchnics, is not followed by glycosuria, although the vaso-motor nerves to the liver are known to pass through them.

According to Eckhard,[3] the phenomena of artificial glycosuria are irritative and not paralytic. This view he believes sustained by his own experiments, according to which if the splanchnics, through which {198} the vaso-motor nerves of the liver pass, are cut prior to the diabetic puncture, not only does this operation fail to produce glycosuria, but it even renders ineffectual the puncture itself as well as the section higher up. But Cyon and Aladoff remind us that it is not mere dilatation of the hepatic vessels, but increased velocity in the movement of the blood, which deranges the sugar-assimilating function and causes glucose to appear in the urine. The vaso-motor nerves of the intestinal blood-vessels also pass through the lower part of the sympathetic and the splanchnics, and section of the latter must cause these blood-vessels to dilate. Now, in rabbits, in which this experiment is usually performed, the digestive canal is very long, and the blood-vessels so capacious that when dilated they hold as much blood as all the rest of the vascular system together, so that when the lower sympathetic and splanchnics are cut, so much blood goes into the intestines that the increased velocity required in the blood-vessels of the liver to produce glycosuria is impossible. But if the vessels of the liver be first dilated by puncturing the floor of the fourth ventricle, section of the sympathetic or of the splanchnics may then be made without arresting the formation of sugar; whence it would appear that the glycogenic influence may still pass through the lower sympathetic and splanchnics.

[Footnote 3: _Beiträge zur Anat. und Physiologie_, iv., 1859, p. 1; vii., 1873.]

In view of the fact that Eckhard[4] has failed to confirm the results of Cyon and Aladoff, but has traced the glycogenic influence down the spinal cord as far as the fourth dorsal vertebra in rabbits, and even a little lower, and that Schiff[5] has shown that diabetes sometimes results after section of the anterior columns of the cord between the medulla and the fourth cervical vertebra, Dr. Brunton[6] suggests that the vaso-motor nerves of the liver may not always leave the spinal cord to join the sympathetic by the branches accompanying the vertebral artery, but sometimes pass farther down the cord, leaving it by the communicating branches to some of the dorsal ganglia, as indicated in Fig. 4.

[Footnote 4: _Beiträge zur Anat. u. Physiologie_, viii., 1877, p. 79.]

[Footnote 5: _Untersuchungen über Zuckerbildung in der Leber_, 1859, S. 108.]

[Footnote 6: _Lectures on the Pathology and Treatment of Diabetes Mellitus_; reprinted from the _British Medical Journal_, 1874, p. 12.]

It is evident that an agency involving any part of this tract in such a way as to paralyze the vaso-motor nerves of the liver is capable of producing glycosuria. Such cause may operate upon the central ganglia whence the nerves emanate, as the vicinity of the oblongata and upper parts of the spinal cord or the coeliac ganglion and its branches, including those to the pancreas. Or the irritation may be peripheral and its effects reflex. We have seen that irritation of the central end of the cut vagus will produce glycosuria. Any irritation, therefore, involving the peripheral distribution of this nerve may produce it. Hence embarrassed respiration, whether due to disease of the respiratory passages, strangulation, or inhalation of irrespirable gases and anæsthetics, produces glycosuria in dogs and rabbits; and this symptom has been known to attend these conditions in the human subject. So, too, glycosuria may be produced by such substances as woorara, strychnia, morphia, and phosphoric acid, introduced into the blood and irritating the terminal filaments of the pneumogastrics, or it may be brought about secondarily through the embarrassed respiration these drugs produce. Such peripheral {199} irritation may reside also in the stomach, intestines, liver, or any organ to which the pneumogastric is distributed.

It is not unlikely that irritation of the extremities of sensory nerves other than the pneumogastric may become the cause of reflex glycosuria. Even puncture of the floor of the fourth ventricle itself may be reflex in its operation, the roots of the pneumogastric being thus irritated. The effect of the irritation conveyed to the glycogenic centre is to inhibit the usual tonic influence of the vaso-motor nerve upon the vessel walls. Among the experimental irritations, in addition to puncture of the floor of the fourth ventricle, which produce glycosuria by reflex action, are injuries of the cerebral lobes and cerebellum, optic thalami, cerebral peduncles, pons varolii, middle cerebellar peduncles, and even of the sciatic nerve and brachial plexus; whence it may be inferred that pathological irritation in the same situations may result in a glycosuria, which is temporary or permanent according as the irritation is temporary or permanent.

Finally, there is no reason why an inhibitory reflex action should not originate in the sympathetic itself. When we remember that this nerve is both sensory and motor in function, and that the inhibitory influence to which the heart's action is subject is accomplished through the sympathetic as a sensory nerve and the pneumogastric as a motor, there is no reason why similar results may not be brought about by the sympathetic alone. This being the case, we need not ascribe glycogenic phenomena to irritation in Eckhard's sense--that is, to a direct stimulant action of the irritant upon the vaso-motor nerves of the liver--but may suppose a sensory influence to ascend one set of sympathetic filaments and an inhibitory influence to descend through another.

Dr. Pavy has recently put forward some chemical theories which explain the action of the hyperæmia in producing glycosuria, but they do not account for the hyperæmia itself. In healthy digestion the carbohydrates (starch and sugar) are converted, not into glucose, but into maltose, C_{12}H_{22}O_{11}, dextrin being intermediate in composition. Maltose is absorbed and assimilated, converted into glycogen. So, too, when glucose is ingested as such, it is converted by the glucose ferment into maltose in the stomach and intestines. For the proper production of maltose and its assimilation a good venous blood, producing a maltose-forming ferment, is necessary. In diabetes, in consequence of the dilatation of the arteries of the chylopoëtic viscera, the blood enters the liver too little deoxygenated, and a glucose-forming ferment is produced. The glucose thus formed is not assimilable, but passes off into the circulation and the urine.

MORBID ANATOMY.--Such are some of the facts bearing upon the pathology of diabetes mellitus. Throwing out the milder type of cases, in which glycosuria is the result of an over-ingestion of saccharine and sugar-producing food--and these can scarcely be called instances of essential diabetes--it is evident that glycosuria may be produced in a variety of ways operating through the nervous system; and accordingly we may infer that there is scarcely an organ in close relation with the sympathetic system derangement of which is not capable of producing it. Among these we would naturally expect to find conspicuous alterations in the nervous centres, and yet I have never found changes in these centres after death. At the same time, others have noted meningitis, tubercular {200} and traumatic, apoplectic effusions, and tumors of the brain, especially in the neighborhood of the medulla oblongata. The alterations in the nerve-centres described by Dickinson as the essential morbid anatomy of diabetes I have looked for in vain. These changes are described as a cribriform or porous condition of the white nervous matter, said to be visible to the naked eye. The spaces thus produced are partially occupied by dilated blood-vessels, which, in turn, are surrounded by dilated perivascular sheaths and broken-down nervous matter, into which extravasations of blood have taken place, as evidenced by the presence of pigment-granules. The changes are found in the white matter of the convolutions of the brain, but fewer and larger in the central portions. The corpora striata, optic thalami, pons, medulla, and cerebellum are favorite seats for the largest and most striking holes. In rapidly-fatal cases the cavities are sometimes filled with a translucent, gelatinous substance, containing, besides vascular elements, the globular products of nervous disintegration. In the more chronic forms of the disease, as it occurs in elderly persons, the excavations are usually empty, although the elements of nervous decay are still to be found fringing the margins or collected as an irregular sheath upon the dilated or shrunken artery. There are changes in the cord similar to those in the brain, but less decided. But the most striking alteration in the cord, according to Dickinson, although not always present, is dilatation of the central canal, which in the dorsal and lumbar regions is sometimes expanded to many times its normal diameter, and forms a conspicuous object immediately after the cord is divided.

These alterations have eluded the vigilance of other pathologists who have sought for them in well-determined cases of diabetes mellitus, while they have been found, on the other hand, in the nervous centres when no diabetes was present. In the recent discussion on diabetes at the Pathological Society of London, Douglas Powell[7] seemed to be the only one who was convinced that most of Dickinson's specimens were examples of positive lesions.

[Footnote 7: _London Lancet_, May 5, 1883, p. 776.]

A hyaloid thickening of the blood-vessels of the brain has been noted by Stephen Mackenzie[8] and Seymour Taylor[9] in some cases, and miliary aneurisms of the retina in one.

[Footnote 8: Discussion on Diabetes, Path. Soc. of London, _London Lancet_, April 7, 1883, p. 593.]

[Footnote 9: Ibid., _Lancet_, May 5, 1883, p. 774.]

Of other organs, one of the most frequently found diseased is the pancreas, and, according to Senator, it is fair to assume that disease of the pancreas is present in about one-half of all cases of diabetes. As the result of increased experience, I am inclined to attach much more importance to pancreatic disease as a cause of diabetes than I did a few years ago. Among the changes found is a pseudo-hypertrophy, which consists chiefly in a hyperplasia of the connective tissue, fatty degeneration of the gland-cells, and atrophy of the glandular structure; cancerous disease; calculous concretions in the ducts with or without obstruction; and cystic dilatation.

Facts bearing upon the relation of pancreatic disease to diabetes have been accumulating since Cowley first discovered calculi in the pancreas of a diabetic, and Bright pancreatic cancer in a similar case. Since then {201} instances have multiplied to such extent that it would be unprofitable to enumerate them. But in 1877, Lancereaux[10] communicated to the French Academy of Medicine specimens of profound lesion of the pancreas from cases dying of diabetes mellitus. This, he alleged, constitutes a special and distinctive variety of diabetes, characterized by sudden onset, emaciation, polydipsia, polyphagia, and peculiar alvine dejections. More recently, Depierre[11] has confirmed these observations, apparently establishing this variety of diabetes mellitus, of which a very rapid course--six months to three years--and the habitual presence of diarrhoea are characteristic; while the presence of greasy or creamy stools, and the appearance in them of undigested nitrogenous substances, may aid in the diagnosis. Precisely such a case, running the same rapid course--less than one year--with emaciation, uncontrollable diarrhoea, creamy stools, jaundice, and pancreatic disease, came under the writer's care in 1882. At the autopsy the pancreas was found enlarged, and numerous gritty particles were disseminated through it.

[Footnote 10: "Notes et réflexions à propos de deux cas de diabète sucre avec altération du pancréas," _Bull. Acad. de Méd._, Paris, 1877, 2d Serie, vi. 1215-1240.]

[Footnote 11: _Med. News and Abstract_, vol. xxxix., June, 1881, p. 344, from _Jour. de Méd. et de Chir. pratiques_, Dec, 1880.]

Supposing such pancreatic disease to be primary, it is evident that it must operate through the coeliac plexus, which, with its ganglion, is gradually encroached upon. On the other hand, it is also possible that the disease of the coeliac plexus may be primary, and the coexisting pancreatic disease and diabetes mellitus both secondarily dependent upon it. This can only be settled by more careful study of the coeliac plexus after death from diabetes, but up to the present time facts would seem to support the view of primary pancreatic disease.

The liver is frequently enlarged--sometimes but slightly, at others decidedly. It has been known to reach three times the size of the normal organ. Again, it may be darker and harder--hyperæmic. By minute examination the acini are found enlarged, the capillaries dilated and distended; the liver-cells are enlarged, distinctly nucleated, rounded, and indistinct as to their outline, appearing to fuse into each other. A weak solution of iodine strikes a wine-red color, which, according to Rindfleisch, is confined to the nucleus, but, according to Senator, may extend to the whole cell. This reaction Klebs ascribes to post-mortem changes in the glycogenic substance. They are more striking in the portal or peripheral zone of the lobule, while the intermediate or hepatic artery zone is often fatty, and the central part, surrounded by the rootlets of the hepatic vein, is nearly normal. Stockvis and Frerichs ascribe the enlargement of the liver partially to a new formation of liver-cells--in other words, to a true hypertrophy. At other times the organ has been found reduced in size.

Dickinson, Trousseau, and Budd describe an overgrowth of connective tissue, as well as of the cells of the liver, producing a hypertrophic cirrhosis.

According to Beale, Frerichs, and Folwarczny, the fat which is found in small proportion in the liver-cells in health is often diminished, and even absent, and quantitative[12] analysis by the last-named observer {202} confirms this view. Such diminution may be the forerunner of an atrophy of liver-cells which has been noted, and which, as the disease continues, leads to the atrophy referred to as occasionally present. On the other hand, intense fatty degeneration of the entire organ, similar to that found in phosphorus-poisoning, has been met by Gamgee, associated with a lipæmic state of the blood and symptoms of acute acetonæmia.

[Footnote 12: Folwarczny, "Leberanalysen bei Diabetes Mellitus," _Wiener Zeitschr._, N. F., 1859, ii. 6.]

The kidneys, in cases which have continued some time, are apt to be hyperæmic and enlarged, although primarily they are uninvolved. It would seem that the long-continued hyperæmia which is a necessary condition of the copious secretion of urine, results, sooner or later, in an over-nutrition of the renal epithelium, a widening of the tubules, and consequent enlargement of the whole organ. The changes are mainly of a parenchymatous or catarrhal rather than an interstitial nature, the epithelium being disposed to shed. These changes may reach a more advanced stage of cellular degeneration, and may be attended by albuminuria. The cells may become very large, present a yellowish-brown color, their nuclei indistinct and non-responsive to ordinary staining solutions, but may take a red stain with a weak solution of iodine, similar to that described in the case of the liver-cells. Mackenzie describes a hyaline degeneration of the intima of the arterioles and a skeleton condition of the epithelium of the collecting tubes.[13] There may also be a catarrh of the pelves of the kidneys and ureters, due to irritation of the saccharine urine.

[Footnote 13: _Loc. cit._]

Atrophy of the testes has been noted by Romberg and Seegen in young men, and recently Hofmeier[14] has reported the case of a young diabetic woman, aged twenty, who came under observation for pruritus vulvæ, in whom the uterus was found small, scarcely 5 cm. (2 inches) long, and the ovaries very much atrophied. As this young woman had no other ailment, the atrophy was ascribed to the diabetes.

[Footnote 14: _Berliner klin. Wochenschr._, 1883, No. 42.]

Among the most constant secondary lesions is the aggregate of changes known as those of pulmonary phthisis. But a few years ago, when our ideas on this subject were more definite than they are to-day, and when it was thought we had three distinct varieties of phthisis--the tubercular, the catarrhal, and the fibroid--the phthisis of diabetes was regarded as typically catarrhal.[15] At the present time, however, when the tendency at least is to regard all phthisis as tubercular, diabetic phthisis must be consigned to the same category. At the same time, if the tubercle bacillus is to be regarded as the essential criterion of tuberculosis, it must be stated that the diabetic patient is subject to two different lung processes--at least if the observations of Riegel of Giessen[16] are to be regarded as correct. In two cases of diabetic phthisis studied at his clinic, the sputum of one contained numerous bacilli, while the other, although the case presented the most distinct signs of infiltration of the apex, and although more than fifty preparations were investigated, revealed none. The sputum was also said to present some unusual physical characters. So far as I know, no autopsies of cases showing these clinical differences have been reported, although there have been found in diabetes, distinct from the usual cheesy foci, fibroid changes with small smooth-walled cavities. In such cases {203} tubercle bacilli would be absent, while the physical signs of consolidation would be present.

[Footnote 15: See the writer's work on _Bright's Disease and Diabetes_, Philada., 1881, p. 256.]

[Footnote 16: _Medical News_, Philada., May 19, 1883, from _Centralblatt f. klin. Med._, Mar. 31, 1883.]

As a part of the phthisical process in diabetes, cavities of various sizes are found and gangrene of the lungs has been observed.

ETIOLOGY.--The problem of the etiology of diabetes mellitus is as unsatisfactorily solved as is that of its pathogenesis. Certainly, a majority of cases of diabetes cannot be accounted for. A certain number may be ascribed to nervous shock, emotion, or mental anxiety; a few to overwork; some to injury and disease of the nervous system; others to abuses in eating and drinking. Among the injuries said to have caused diabetes are blows upon the skull and concussions communicated to the brain, spinal cord, or vaso-motor centres through other parts of the body. Hereditation is held responsible for a certain number of cases. Malarial and continued fevers, gout, rheumatism, cold, and sexual indulgence have all been charged with producing diabetes.

Diabetes mellitus is most common in adult life, although Dickinson reports a case at six years which was fatal, Bence Jones a case aged three and a half, and Roberts another three years old; and in the reports of the Registrar-General of England for the years 1851-60 ten deaths under the age of one and thirty-two under the age of three are included. This statement, in view of the experience of the difficulties of diagnosis in children so young, seems almost incredible. I have never myself met a case in a child under twelve years. At this age I have known two, of which one, a boy, passed from under my notice, while the second, a girl, recovered completely. The disease is most common between the ages of thirty and sixty. The oldest patient I have ever had died of the disease at seventy-two years, having been under my observation for three and a half years.

It is decidedly more frequent in men than in women, carefully prepared statistics of deaths in Philadelphia during the eleven years from 1870 to 1880, inclusive, giving a total of 206 deaths, of which 124, or three-fifths, were males, and 82, or two-fifths, females. This is the experience of all.

My own experience has been singular and interesting. Up to April, 1881, I had never met a case in a woman. Of 18 cases outside of hospital practice which I have noted since that date, 9 were men and 9 women. But I still do not recall an instance of a woman in hospital practice, although I have constantly cases among men.

Not much that is accurate can be said of the geographical distribution of the disease. It seems to be more common in England and Scotland than in this country, at least if the statistics of New York and Philadelphia are considered. In the former city, statistics extending over three and a fourth years show that out of 1379 deaths, 1 was caused by diabetes; in Philadelphia, in eleven years, 1 out of 875; in England and Wales, according to Dickinson from observations extending over ten years, 1 out of 632; and in Scotland, 1 out of 916. According to the same authority, the disease is more prevalent in the agricultural counties of England, and of these the cooler ones, Norfolk, Suffolk, Berkshire, and Huntingdon. According to Senator, it is more common in Normandy in France; rare, statistically, in Holland, Russia, Brazil, and the West Indies, while it is common in India, especially in Ceylon, and relatively very frequent in modern times in Wurtemberg and Thuringia. Seegen says it is more {204} frequent among Jews than among Christians, but I have never seen a case in a Hebrew.

SYMPTOMS, COURSE, AND DURATION.--The earliest symptom commonly noted by the diabetic is a frequency of micturition and the passage of larger amounts of urine than is natural. Coincident with or immediately succeeding this is an undue thirst and dryness of the mouth, which soon becomes the most annoying symptom the patient has, the freest draughts of water giving but partial or temporary relief. To this succeeds dryness, and sometimes itching, of the skin and absence of perspiration. A good appetite with fair digestion accompanies this stage of the disease, but notwithstanding this the patient loses in weight. If a male, his attention is sometimes called to his urine by the white spot left after the evaporation of a drop of urine on his boot or clothing or by the stiffness of his linen due to the same cause. To these symptoms are sometimes added an intolerable itching of the end of the urethra in males and of the vulva in females, probably due to the irritation caused by the saccharine urine in passing over and drying upon these parts.

As the disease progresses muscular weakness supervenes. This, however, comes on at varying periods after the incipient symptoms make their appearance. Sexual inclination grows less. The muscular weakness gradually increases, if the disease is not checked, until the patient can barely walk: he totters in his gait, and reminds one of a case of Duchenne's disease. Even before this he sometimes gives up and goes to bed. Often harassing cough ensues, adding its exhausting effect to that of the essential disease. Percussion and auscultation discover consolidation at one apex or over larger areas of the lungs. Dyspepsia and indigestion replace the good appetite which attended the onset of the symptoms, and all efforts to increase the latter are unavailing. The heart begins to flag, and its action is irregular. It finally ceases to act, and the patient dies suddenly, sometimes unexpectedly. Or coma may supervene before death. This coma, known as diabetic coma, is generally ascribed to the accumulation of acetone or acetone-producing substance in the blood. It is supposed to be a product of the decomposition of the sugar in the blood, and the phenomena resulting from its presence are known as those of acetonæmia. Some further account of it will be given in the section on changes in the urine. It is sometimes recognizable by a fruity odor of the breath, which may even pervade the atmosphere of the room in which the patient lies, and may be recognized on entering. It has been compared to the odor of a room in which apples have been kept, again to sour beer, and again to chloroform.

During all this time the thirst and discomfort arising therefrom, continue, although it sometimes happens that toward the end the quantity of urine and its contained sugar diminish and the urine becomes darker in hue.

Such is the course of a typical case of diabetes mellitus. Other symptoms, less conspicuous, are a lowered temperature of the body, from 1° to 2½° F. or even more; cataract, dilatation of the retinal vessels, intraocular lipæmia, functional derangements of vision, including amblyopia, presbyopia, and loss of accommodating power; and occasionally total blindness from atrophy of the retina may be present. I have known almost total blindness to appear very early in the disease, and {205} subsequently to disappear. Derangements of the other special senses, as impairment of hearing, roaring in the ears, and disorders of smell and taste, also occur. Boils and carbuncles are occasional symptoms; although usually late in occurrence, the former are said to be sometimes the first symptoms recognized. Numerous skin affections may occur. Ulcerated surfaces are slow to heal, and gangrene supervenes sometimes spontaneously, but more often as the result of some trifling injury. It may start from a blister produced by cantharides, although such instances are scarcely frequent enough to justify interference with treatment demanding blisters. More frequently surgical operations do badly. Allied to this tendency is a spongy state of the gums, with recession and excavation, resulting, in asthenic cases, in absorption of the alveolar processes and falling out of the teeth. Eczema of the labia and vicinity in females, and a similar irritation about the meatus urinarius in males, are annoying symptoms. A purulent-looking discharge has been seen issuing from the urethra, in which the spores of penicilium glaucum have been recognized by the microscope.

The term diabetic coma is applied to a form of coma which is apt to occur late in the disease, indeed most frequently to terminate it; while it is also used to indicate a train of nervous symptoms of which coma is the terminal one. To this train of symptoms the word acetonæmia is also applied, and should alone be used, while the term diabetic coma should be restricted to the terminal symptom. The coma, as well as the previous nervous symptoms, is considered due to the accumulation in the blood of a product of the decomposition of sugar, formerly believed to be acetone, but now thought to be an acetone-producing substance, probably aceto-acetic acid. It is likely that in all cases of diabetes a small quantity of this substance exists in the blood, from which it is separated by the kidneys and lungs, while it is only when these channels are insufficient for its removal that it accumulates and produces the symptoms described.

Usually, the coma comes on gradually, deepening until it terminates in death. In other instances it is preceded by various symptoms, including dizziness, drowsiness, cephalalgia, delirium, mania, muscular pains, gastric and intestinal symptoms, including epigastric pain, vomiting--sometimes of blood--and even purging; also dyspnoea, with short, panting respiration like that of an animal with both vagi cut, and a fluctuating pulse-rate which continues until coma is established, after which it remains rapid and small. Both the breath and urine may exhale the peculiar odor of acetone, or it may be absent, and the urine strikes the peculiar burgundy-red reaction with perchloride of iron to be again referred to.

These symptoms may be sudden in their occurrence, whence acute acetonæmia, or they may ensue slowly. Ralfe,[17] who has studied the subject of acetonæmia very thoroughly, has called attention to the parallelism between the phenomena of acute acetonæmia and those of acute yellow atrophy of the liver and of phosphorus-poisoning. The sudden, sharp epigastric pain, with gastric disturbance and vomiting, often of blood; the peculiar panting dyspnoea referred to; the short, {206} noisy delirium, followed almost suddenly by deep coma; the fall in temperature as the nervous symptoms develop; the irregular, and finally rapid, pulse,--are all symptoms common to the two conditions.

[Footnote 17: _Clinical Chemistry_, 1883, p. 98; also Discussion on Diabetes before Pathological Society of London, _Lancet_, April 7, 1883, p. 592.]

Although acknowledged to be a grave complication, and the most frequent cause of death in diabetes,[18] yet it does not follow that a fatal termination is inevitable when diabetic coma sets in. I have now a patient, a woman, who considers herself in perfect health, but in whom there remains a trifling glycosuria, who at one time was supposed to be dying of diabetic coma.

[Footnote 18: Of 400 cases of diabetes which passed under the observation of Frerichs, the majority died of acetonæmia (Frerich's "Ueber den plötzlichen Tod und über das Coma bei Diabetes," _Zeitschr. für klin. Med._, 1883, vi. 3-53). Of 53 persons dying of diabetes at Guy's Hospital, London, during the last ten years, 33 died comatose (Dr. Fred. Taylor, Discussion on Diabetes, Pathological Society of London, _Lancet_, May 5, 1883). In my own experience acetonæmia has not been so frequent a cause of death as phthisis, acute pneumonia, and heart-failure.]