386 PATHOLOGY functions with whose disorders are associated some of the severe diseases of common occurrence, taking them accord ing to the organs, and taking the liver first. The liver-structure is very much that of a blood-gland ; its system of bile-ducts is subordinate to its blood-system, just as its biliary function, though the amount of its product be great, is in modern physiology subordinate to its glyco- genic. Except in connexion with JAUXDICE (*/.? .), the biliary function does not concern us ; we come at once to the not uncommon and very serious malady which may be regarded as an error of the glycogenic function, namely, diabetes. Dia- Diabetes. Like the errors of metabolism treated of in previous betes. sections, diabetes is a "constitutional " or general disease. It depends essentially upon the circumstance that the blood passing to the kidney is overcharged with sugar ; the kidney drains off the sugar along with an immense quantity of water, so that the prominent symptom is copious urine loaded with sugar. Diabetes can hardly be called a disease of the kidneys ; these organs are but the ministers of disordered metabolism whose seat is elsewhere, and their structure is not even materially altered in the disease. In pronounced dia betes sugar is everywhere. There may be half a per cent, of it in the blood, it is in all the tissue-juices and in all secretions, and it may enter into the composition of the urine to as much as 10 per cent. The diabetic patient drinks enormously (the thirst being due, it is conjectured, to the more concentrated state of the sugary blood), and eats or desires to eat two or three times more than in health ; the amount of urine voided is proportionately great, and it contains a total of urea in the twenty-four hours which corresponds approximately to the high feeding. All the while there is no proper nutrition ; the body wastes, the skin becomes dry, the hair falls out, the muscles become flabby, the heart s action is weak, and the secreting organs become reduced in bulk and enfeebled in func tion. AVounds tend to become gangrenous, boils and carbuncles are apt to form, and pulmonary consumption is a frequent com plication. The saccharine state of the fluids is favourable to the lodgment of fungi (moulds), and these are found in the centres of disease in the lungs. The disease is an example of those paradoxes that we frequently come to in the last resort in the analysis of con stitutional disturbances ; in spite of the enormous supplies that the organism demands (and receives), the tissues and organs are not nourished. It is only in some cases that the disease is checked by a pure nitrogenous diet. There is some maladaptation in the economy whereby there is an enormous quantity of sugar produced which is not wanted, and a great lack of that which is wanted. AVhere does the divergence occur from the physiological track ? The blood ordinarily contains a trace of sugar, and traces of it may be discovered in the urine. It may be permitted to regard these traces as no more than the slight margin of non-perfect adapt ation which is discoverable in many structural and functional effects. But the antecedent of this sugar, namely glycogen, exists in considerable quantity in animals the moment after death, and . is assumed to exist in them during life. Although this assumption must be granted, it is not so justifiable to admit, with some authors, that the glycogen of the body is normally changed into sugar, the latter being at once disposed of in the further course of combustion. Glycogen is now known to exist in various tissues, more parti cularly in inactive muscle ; but it is impossible not to conclude, on the evidence, that the liver is still the organ of its choice ; and Ber nard s original position, that diabetes is a disorder of the glycogenic function of the liver, may be regarded as the reasonable one. The structure of the liver is in great part an adaptation to some such metabolic function, an adaptation to take somewhat from the blood and to add somewhat to the blood again. The intermediate state of this metabolism is glycogen, a starchy substance which changes to sugar under the action of a ferment out of the body, and changes to sugar sometimes in the body. Various kinds of interference canse glycogen to change to sugar within the body puncturing the medulla oblongata at a particular spot with a fine spear-like point ; the administration of curare, whose chief action is to paralyse the muscles through their nerves; the administration of nitrite of amyl, whose more owious effect is vaso- motor paralysis of the surface- vessels, causing dilatation of them. These interferences produce a passing diabetes. It has been objected that the diabetes so pro duced is too transitory to be counted as analogous to the grave human malady ; but it is well known that the same transitory effects are not uncommonly met with in medical practice. The time and serious diabetes is merely the established and confirmed habit of turning everything to sugar, and it cannot be doubted that Bernard s original experimental analogies are still the best clue to the nature of the disease. These experimental interferences point to some profound upset of the nervous control. The spot in the medulla where puncture causes temporary diabetes is otherwise known to be the vaso-motor centre ; the effects of nitrite of amyl are otherwise such nerve -effects as blushing ; the several effects of curare are identical with the muscular limpness of fear. The observations of clinical medicine point in the same direction ; a large proportion of all the cases of diabetes where the antecedents have been ascertained with any degree of relevancy are cases of profound emotional and intellectual strain, of shocks and jars and worries to the mind, and especially to the primary instincts and affections. Along with these we have a few significant cases of tumour in, or upon, or in the neighbourhood of the medulla. These clinical facts point clearly enough to some upset of the nervous control, although there are certainly few or none of the usual concomitants of nervous disturbance. The nerve- paths that are implicated are the same as the vaso-motor ; but the effects themselves are not vaso-motorial. Nitrite of amyl causes artificial blushing, and it also causes diabetes ; in like manner those subjective states of the mind (or mechanical states of the brain) which ordinarily take such outward directions as blushing and pallor, or the vaso-motorial direction, sometimes spend themselves otherwise, causing an upset of the glycogenic adaptation. It is cer tainly not a simple affair of vaso-motor paralysis, even if the path of influence be the same. Some nervous mechanism allied to the vaso-motor, or using the same path of influence, is probably con cerned, the same kind of unknown nervous mechanism which would appear to be concerned in Addison s disease (of the supra renal) and in Graves s disease (of the thyroid). The upset of this controlling nerve-force is followed by the production of a substance from the liver-cells which is directly added to the blood as sugar, and is removed as sugar in the urine. This substitution of sugar in the blood for some other substance is fatal to nutrition ; it is so wasteful an expenditure that the physiological bankruptcy cannot be averted even when the patient receives the enormous amount of food and drink for which he craves. For the pathology of diabetes the obvious desiderata are to know the normal sources and normal ways of disposal of the glycogen of the liver. It seems to be premature to infer that, because gly cogen, as its name implies, may easily become sugar, therefore it ordinarily does become sugar as a transition -stage towards some other product. If the regular conversion of glycogen into sugar be assumed, the cause of diabetes would be referred to the inadequate disposal of the sugar (e.g., its inadequate combustion in the lungs). Cohnheim, after summing up the evidence from all sources, con cludes that such inadequate disposal of sugar, properly present in the bodj r , does occur in diabetes ; and he would seek for the reason of the failure in the want of some "ferment" which, in health, brings about the further breaking up of the sugar. The question, how ever, is a sufficiently open one for us to contend that the initial error lies in the making of sugar at all ; or, in other words, that the failure of the ferment (or of the nerve-control of metabolism) has to be assigned to an earlier stage of the metabolic process. It is probably more than an accidental coincidence that the pancreas has often been found shrunken and indurated in diabetes, the shrinkage having followed apparently on an earlier hyperplasia. According to analogy it would mean that the error of the hepatic function had thrown more work upon the pancreas. Apart from the state of the pancreas there is nothing distinctive in the struc tural conditions associated with diabetes. Acute Yellow Atrophy of the Liver. Here we have another severe Acut constitutional disorder, but much rarer than diabetes, in which the yelk hepatic functions are chiefly, and perhaps primarily, concerned, atroj It arises under a variety of circumstances, the chief of which are of li- respectively poisoning by phosphorus, profound emotional troubles, and the state of pregnancy. The early implication of the hepatic functions is shown by the existence of a degree of common jaundice for some time before the distinctive and fatal onset. The disease may be said to consist in a complete disorganization of the whole hepatic activity, in the arrest of its biliary secretion and of its other metabolism. The liver- cells fall into a state of molecular disintegration, and the organ shrinks bodily, sometimes to a mere fraction of its original volume. The ducts contain no bile, but a colourless plasma in place of it ; the cells, where they keep their outlines, are full of allmminous granules; large quantities of leucin and tyrosin are found in the organ after death. "What is there common to phosphorus -poisoning, profound emotional troubles, and the state of pregnancy which can be brought into relation with this remarkable upset of function and rapid disintegration of structure ? As regards the effects of phosphorus, they belong to a remarkable class of effects, counterfeiting idiopathic diseased states, which it is the property of certain of the chemical elements, inchiding arsenic, antimony, and lead, to induce. The action of this element may be said to be an arrest of metabolism, falling with special stress upon the great seat of such functional activity (and on the secret ing cells of the stomach and kidney as well). As regards the acute yellow atrophy of the liver which follows profound emotional troubles, we have many slighter analogous instances of nervous inhibition of visceral function due to more transitory states of emotion ; the disorganization of the liver -function would be the proportionate effect of a more profound and more lasting mental
