FUNCTIONAL DISORDERS OF THE LIVER.
MELLITURIA, GLYCOSURIA, DIABETES MELLITUS, SACCHARINE URINE.
Source of glucose in food. Glycogen: Its use: Enlarged liver means more glycogen. Glycosuric centre in medulla. Other glycosuric nerve centres. Reflex action, action of drugs and poisons, phlorizin. Disease of lungs or pancreas. Removal of pancreas in dogs. Removal of thyroid. Diseased, liver, fatty, fibroid, hypertrophy, congestion. Extreme fatty change arrests glycogenesis. In solipeds: 3 cases with liver hypertrophy; 1 case with adenitis; 6 cases with emaciation; 2 cases with hæmoglobinuria. Symptoms: Emaciation, debility, langor, fatigue, breathlessness, hollow flanks, unthrifty skin, ardent thirst, polyuria, urine saccharine, of high density. Diagnosis by analysis of urine, sweet taste, Fehling’s test, Trommer’s test, fermentation test. Prognosis: Grave, diet being carbonaceous, when functional resulting from curable disease is hopeful. Treatment: In poisoning cases, antidotes and eliminants, in curable disorders treat these, in more inveterate cholagogues, antiseptics, codeine, opium, croton chloral, strychnia, phosphoric acid, iodoform, ergot, skim milk or buttermilk, good hygiene, open air, shelter, carminatives, bitters, mineral acids, treat complications.
Grape sugar (glucose, C6H12O6) is undoubtedly formed in the stomach and intestines by the action of saliva and pancreatic juice on starch (C6H10O5), and glucose and laevulose (C6H12O6) are also derived from the transformation of cane sugar (C12H12O11). These sugars are absorbed, transformed into glycogen in the liver and passed into the circulation, where they serve to maintain animal heat through their decomposition into carbonic acid and water. They further assist in nutrition and growth, and if their metamorphosis is imperfect they pass out of the system in the urine, producing a temporary glycosuria. As shown above glycogen is produced in the liver cells, and stored up there, in greatest abundance during digestion of starchy and saccharine food, but it is also formed in animals kept on a purely albuminous diet, (flesh), and in the fœtal calf and unhatched chick to which neither starch nor sugar has been furnished as food. It is produced during the decomposition of albuminoids, along with the other end products, leucin, tyrosin and urea. None of these last three is found in the portal vein nor bile ducts, but all four are found in the liver cells, and in the hepatic veins.
In health a physiological balance is maintained by the oxidation of the glucose, mainly in the lungs, so that in the blood of the pulmonary veins no sugar is found. There is an exception to this observable after a full meal, rich in starch and sugar, which produces such an excess of glycogen that a portion is carried to the kidneys and expelled by them causing temporary glycosuria.
A small amount of glycogen is also produced habitually by the white blood cells and stored up in them, but this is insufficient to determine its appreciable elimination by the kidneys.
In cases of persistent glycosuria the fault may be held to consist in one of three functional derangements:
1st. The failure of the liver to transform the alimentary sugar into glycogen.
or 2d. The excessive production of glycogen in the liver.
or 3d. The arrest of the destructive oxidation of sugar in the lungs and tissues.
In a diabetic patient who died suddenly of apoplexy Bernard found that the liver was enlarged, comparing with the average as 25:14 while the contained sugar bore the ratio of 37.5:22. This enlargement coming from malaria or other poison, such as alcohol, ether (Harley), arsenic, quinia (Aitken), ammonia, chloroform, or phosphoric acid (Murchison), is an established condition of glycosuria. A rich and abundant food (starchy and saccharine especially), or an unusually active hepatic circulation acts in the same way.
Bernard as early as 1849 showed that the glycogenic function of the liver was greatly increased and glycosuria determined by pricking the floor of the fourth ventricle in the median line just in front of the calamus scriptorius and near the root of the vagus nerve, or a few millimeters in front of this.
It follows that irritation of this part of the medulla however produced, whether from local disease, or by reflex action from some distant organ in a state of irritation, may serve as the starting point of diabetes in particular instances. That the cause may be a reflex stimulus is shown by the suspension of the glycogenic function after section of the vagus nerves, and its reappearance when the central end of the cut vagus is galvanized, or, the floor of the fourth ventricle is irritated, the direct or efferent excitation being transmitted through the sympathetic nerve (Bernard). I can cite a case of glycosuria in a man supervening on a severe blow on the head from a falling ledger. Brain injuries which suspend animal functions, but not the nutritive ones, such as apoplexy, concussion of the brain or curare poisoning are liable to induce diabetes.
Traumatic injuries to other parts of the nervous system induce glycosuria. Thus traumatism of the optic thalami; of the cerebral lobes or peduncles; of the pons; of the cerebellum or of its middle or posterior peduncles; transverse section of the medulla or of the spinal cord opposite the second dorsal vertebra; traumatism of the superior or inferior cervical ganglion or the first thoracic (Eckhard); of the sympathetic twig which accompanies the vertebral artery (Pavy); of the brachial plexus; of the solar plexus (Munck, Klebs); or of the sciatic nerve (Schiff).
The explanation of these facts may be sought in a reflex action established by the conveyances of irritation to the true glycogenic centres in the brain and the transference of the efferent nervous impulse through the sympathetic nerve to the liver. It will be borne in mind that in the case of section of the vagus nerve electric stimulation of its detached peripheral part has no glycogenic effect on the liver, while galvanizing the central portion determines glycosuria.
In the case of glycosuria through stimulation of the sympathetic nerve or its ganglia the action may be concluded to be direct. Strangely enough, irritation of the sympathetic between the tenth and twelfth ribs or the splanchnic nerves fails to produce glycosuria, though the hepatic branches of the sympathetic pass through them.
In ordinary cases of reflex glycosuria it may be assumed that the existence of irritation at the peripheral ends of the vagus and of some other nerves, leads to an apparent glycogenic influence passing through these to the brain, and of the distribution of the efferent impulse through the upper portion of the spinal cord, as far as the fourth dorsal vertebra in the rabbit (Cyon, Aladoff, Schiff), and through the sympathetic nerve to the liver. This may account for the appearance of the disorder as a sequel of disease in any part to which the vagus in particular is distributed, and notably in the lungs. A number of poisons (malarial, alcoholic, ether, carbon monoxide, amyl nitrate, curare, or the nitro-propionic acid, methyl delphinin, morphia, chloral hydrate, arsenic, quinia, ammonia, chloroform, phosphoric acid, and phlorizin) produce glycosuria.
The intravenous injection of dilute saline solutions, or frequent blood letting materially increases the sugar, probably by causing solution of the red globules. Phlorizin is the most potent of all these agents. Whether given hypodermically or by the stomach it causes in three hours a marked production of glucose which continues to be eliminated for a period of thirty-six hours. The urine may become charged with glucose to the extent of from 6 to 13 per cent., and without any rise in the body temperature. This artificial glycosuria may be kept up indefinitely by the continued administration of phlorizin, and even in the fasting animal, or one on an exclusively albuminous diet, as well as in those on an aliment rich in saccharine or hydro-carbonaceous matter. In the frog it produces diabetes even after the extirpation of the liver showing that it stimulates other sources of sugar production beside the hepatic or that it inhibits the transformation of sugar derived from the alimentary canal and other sources.
Another suggestive source of mellituria is disease of the lungs, or any condition which interferes with the due æration of the blood and oxidation of the alimentary or hepatic sugar. But it cannot be assumed that the rôle is altogether or mainly chemical. The thoracic organs being supplied by branches of the vagus and sympathetic nerves there is the obvious suggestion of a reflex action through the diabetic centers in the brain. The frequent complication of diabetes with lung diseases (inflammatory, tubercular, syphilitic, and otherwise) is abundantly proved, whether it is to be explained on the above hypothesis or through other unknown changes in the blood.
Diabetes has been repeatedly found in connection with disease of the pancreas, and the complete extirpation of the pancreas in dogs gives rise to glycosuria (Mering and Minkowski, Thiroloix, Lancereaux, Lepine). If a small portion of the pancreas remains glycosuria does not supervene. It has been suggested that the pancreas has a double function, and beside its secretion, produces a glycolytic ferment which passing into the portal blood determines the formation of glycogen in the liver. Arrest of the pancreatic secretions does not cause glycosuria, so it has been suggested that the glycogenic enzyme is a product of the connective tissue cells of the pancreas. Functional as well as structural disease of the pancreas can be conceived of as inhibiting the production of this ferment and the consequent elaboration of glycogen. Chauveau and Kauffmann deduce from their observations that the action is a reflex one established through the glycogenic centres in the medulla. Pancreatic glycosuria is especially fatal (Harley).
Finally extirpation of the thyroid body in dogs has been followed by glycosuria (Falkenberg). This suggests a systematic examination of the urine in all cases of goitre, with extensive glandular changes.
Apart from experimental cases diabetes in the lower animals has been observed to be nearly always associated with diseased liver. Fatty degeneration has been the most frequent lesion, but cirrhosis, hypertrophy and congestion were present in other cases. In a number of cases as the fatty degeneration reached an extreme degree, the sugar disappeared from the urine, the hepatic cells being no longer functionally active, and death speedily followed. The same has been observed in the fatty degeneration attendant on poisoning by arsenic or phosphorus.