Chapter XVII: Part 17

_Lesions._ The liquid exudate has been found to amount to 30 or 40 quarts in large dogs (Hordt). It is often clear and translucent, of amber tint, though in some cases it is slightly opaque, or reddish yellow. It may remain fluid after extraction or again it may form a loose jelly. It may be red in case of soft tumors or other neoplasms. The liquid is very watery but may contain a considerable amount of fatty globules or granules, and a few epithelial cells and leucocytes. The peritoneum is pale or in advanced cases dull white from fatty degeneration of the epithelium.

_Treatment._ The first consideration is the removal of the cause. If this is a mere vicious action of the peritoneum, or the presence of a thrombus, or of operable tumor, or even of curable disease of the liver or kidneys, success may be hoped for, while in dilatation of the heart, insufficiency of the cardiac valves, irremediable disease of the lungs, liver or kidney, or malignant or inoperable tumor no such result can be hoped for.

Apart from the removal of the cause the first indication is to evacuate the liquid and this may be done with a large hypodermic needle or small cannula and trochar inserted by preference on or near the linea alba while the animal is in a standing position. Skin and instrument should be rendered thoroughly aseptic, and a bandage should be wrapped round the abdomen and gradually tightened as the liquid escapes. This to a large extent obviates the tendency to faint, or to cerebral anæmia which has caused sudden death in a number of cases. It also to some extent counteracts the sudden effusion of blood in the abdomen, which is at times determined by the sense of vacuity.

Injection of a solution of iodine (tincture of iodine 1 pt., iodide of potassium 1 pt., boiled water 20 pts.) has been employed sometimes with success, but in other cases it has roused a fatal inflammation. It is best adapted to a simple morbid, relaxed state of the peritoneum.

Saline purgatives (sulphate of soda or magnesia) are especially useful in constipated cases and should be pushed in continuous action, as far as the strength of the animal will warrant. By depletion from the portal system they oppose the tendency to mechanical transudation, while by rendering the portal blood more dense they strongly solicit endosmosis from the adjacent peritoneum.

Diuretics have been used extensively and with benefit. They may prove injurious in a kidney that is already the seat of irritation and yet after all be the least of two evils. In some cases instead, the resulting dilution of a dense and irritating urine is directly soothing to the tender kidney. Saltpeter (10 to 15 grs.), acetate of soda (15 to 30 grs.), squills (1 to 2 scr.), may be repeated so as to keep up a free action. Pilocarpine (subcutem) (¹⁄₁₀₆ to ¹⁄₃₀ gr. daily), has removed the ascitic fluid in 14 days (Zahn), but its action is always to be dreaded in a weak system, or with a diseased heart, or lungs.

A supporting bandage on the abdomen is always useful as counteracting the tendency to vacuity and further transudation.

A course of bitters and iron, and a supporting diet, and out door life (sunshine) are important elements in treatment.

DISEASES OF THE LIVER.

In veterinary and medical works the diseases of the liver have been accorded a minor place, ill in keeping with the great physiological importance of the organ. If the function of the liver were circumscribed by the mere secretion of bile there would be some excuse for the apparent neglect, as the gland is so deeply situated and so much enveloped in surrounding organs that physical exploration is difficult and somewhat unsatisfactory, and the one symptom of jaundice was long relied on as indicating hepatic disorder.

Taking into account all the varied functions of the liver we realize the wide-reaching nature of its physiological influence and the extensive and varied effect of its disorders. We can also deduce, with greater or lesser certainty, the existence of hepatic disorders from the morbid conditions of the blood or of organs, the functions of which are inter-dependent with those of the liver. To elucidate the subject it is well to trace some of the most prominent functions of the liver; the following considerations are submitted.

SANGUIFICATION IN THE LIVER.

Glycogenic function. Glycogen derived through glucose and laevulose
from starch, glycerine, milk and cane sugars. Less from proteids.
Peptones as a source. Its use in cell growth and heat production, in
white blood cells, in contracting muscle, becoming lactic acid. Excess
dissolves red globules, setting free hæmoglobin. Ammonia carbonate and
asparagin increases it. Arsenic, phosphorus or antimony arrests
glycogenesis. Liver increases leucocytes, and reduces size of red
globules. Reduction of proteids. Fibrine formers reduced, urea formed;
liver inactivity means less of soluble urea, and more of less soluble
and more dangerous products. Urea increases with hepatic circulation.
Hepatic disorder and suppression of urine dangerous. Red globules
probably destroyed. Bile: Amount, uses, oil solvent, helps endosmosis,
deodorant, stimulates glycogenesis, excretory. Source of bile
pigments, tests. Bile acids, dissolve blood globules, antiseptic,
tests. Bile increased by; bile absorbed from bowel, olive oil, salol,
salicylates, benzoic acid and benzoates, turpentine, terpene,
terpinol, euonymus, alkalies, arsenic, ether. Agents lessening biliary
secretion, starvation, excess of fat, alkaline iodides, atropia,
strychnia, hepatic diseases, septic duodenal fermentation. Arrest in
liver of copper, iron, iodides, bromides, nicotine, quinine, morphia,
curare, toxic bile products, ptomaines, toxins. Reduces toxicity of
peptones, casein, ammonia salts, indol, phenol.

The liver is the goal to which most of the products of gastric and intestinal digestion are carried by the portal vein. In the hepatic cells large quantities of _glycogen_, 6 (C_{6}H_{10}O_{5}) + H_{2}O, are stored up after each meal. This is believed to be derived largely from the transformation of glucose, (C_{6}H_{12}O_{6}) and laevulose (C_{6}H_{12}O_{6}) which have been produced from starch in the alimentary canal and conveyed by the portal vein to the liver. By the liberal use of starch, glycerine, or the sugars of milk, fruit or cane, (but not mannite, or glycol, or inosite) the glycogen is very greatly increased (to 12 per cent. in the fowl), but it is diminished on a purely albuminous diet. Yet it can be produced from albuminous food, as it is always increased in the dog after a meal of flesh, and is largely present in the livers of carnivorous animals that have been fed for a month on flesh only (Landois). The peptones are therefore decomposed in the liver with the production of glycogen and such waste products as leucin and tyrosin, which are finally resolved into urea. A purely fatty diet diminishes it enormously and during prolonged abstinence it practically disappears. It passes, not into the bile, but into the hepatic veins, and the general circulation, where it serves in its decomposition to generate heat, and probably to hasten cell growth. In the vegetable and animal world, in the germinating seed, and in cartilage, muscle and epidermis of the fœtus and in the amnios, glycogen and glucose are found in abundance. The liver, too, the great center for the production of glycogen, is relatively much larger in the young and growing animal, and also in the adult animal which has great power of assimilation.

Glycogen is always present in the white blood globules so long as they maintain their vitality and amœboid movements, but when they die, it is replaced by sugar (Hoppe-Seyler). The red blood globules give up a ferment which rapidly transforms glycogen into sugar.

Glycogen and sugar are evidently of use in muscular contraction as they are always diminished in the vessels of contracting muscles (Sanderson), being converted into lactic acid (Bernard).

Forced muscular movements soon expel glycogen from the dog’s liver, passing it into the blood, and there the excess of glycogen dissolves the red blood globules. If glycogen is injected into the blood, achrodextrin and hæmaglobin appear in the urine (Landois).

Ammonia carbonate and asparagin, or glycin, with a carbhydrate diet produced in rabbits a considerable increase of glycogen (Rohmann).

Poisoning by arsenic, phosphorus or antimony destroys the glycogenic function of the liver, which then fails to respond even to diabetic puncture of the medulla.

There are important changes effected in the blood globules in passing through the liver. The _leucocytes_ are increased, the hepatic veins containing 5 or even 10 times as many as the portal vein (Bernard, Lehmann, McDonald). Their ratio to the red globules is in the portal vein 1:524 and in the hepatic veins 1:136 (Hirt). The _red globules_ undergo marked changes, having, in the hepatic veins, a smaller size, sharper outlines, less flattening in the disc, a habit of massing together irregularly in place of adhering in rouleaux, and they dissolve less readily in water.

REDUCTION OF ALBUMINOIDS.

A large proportion of the fibrine formers are changed in passing through the liver (Lehmann, Bernard), in man as much as 2,690 grammes daily (Brown Sequard), a fact which goes to account for the increase of fibrine in inflammation when the liver is inactive. The change consists mainly in deoxidation and reduction into simpler compounds which can be more readily dissolved and eliminated. Arrest of the liver functions in fever is therefore liable to throw into the blood, products that are little soluble and often poisonous. The end product is largely urea, and this Cyon always found in excess in the hepatic veins of dogs (in the portal veins 0.08 grammes, and in the hepatic veins 0.14 to 0.17 grammes). In man hepatic disorder is at once marked by the lessening or disappearance of urea from the urine, and the increase of the less oxidized uric acid (Parkes). In acute atrophy of the liver, urea disappears from the urine, being replaced by the less oxidized leucin and tyrosin (Frerichs, Murchison). In birds urea is replaced by uric acid and this is always found in the liver.

The increase of urea and allied products bears a direct relation to the activity of the hepatic circulation. Stimulation of the liver by electric current sent through the abdominal walls largely increased the secretion of urea (Sigrist, Stolnikow, Schröder and Salomon). Murchison, Perrin and Bruardel had a great increase of urea by stimulating the circulation in the liver. Certain agents ingested are transformed into urea, among which may be named glycocolle, brucin, asparagin, sarcine, alanine, and ammonia muriate.

Any degeneration of the hepatic cells which impairs or arrests their functions lessens the production of urea. In fevers therefore and in hepatic degenerations the extent of the functional or structural derangement may be to a large extent gauged by the diminution of urea. A simple hyperæmia, without as yet any serious impairment of structure or function, may be attended by a marked increase of urea, whereas any destruction of the liver cells, or any serious modification which interferes with the normal function, brings about a decided decrease. A hepatic disorder accompanied by suppression of urine is always a grave disorder. On the contrary a free secretion of urine during liver disease is a favorable symptom.

There is reason to believe that red blood globules are destroyed in the healthy liver, producing bilirubin and urea (Landois). In diseased states this becomes excessive, and the resulting coloring matter is often modified, giving the strong tints, seen in the urine in fever and certain hepatic disorders.

SECRETION OF BILE.

The secretion of bile is but a small part of the function of the liver, and that is by no means a purely eliminating process. Man secretes in twenty-four hours about 10 parts per 1,000 of body weight, the dog 14 to 15, the cat 15 to 20, the sheep 25, the rabbit 130, the Guinea-pig 170, the goose 12 (Cadeac), the horse 12 (Colin). But the amount varies largely; Scott found that a dog yielded 21, and Kölliker that another yielded 36 per 1,000 of the body weight.

Only about one-fourth of the biliary acids (Bischoff, Voigt), and one-eighth of the sulphur (Bidder and Schmidt) of the bile can be found in the fæces. Most of the bile is re-absorbed from the intestine and secreted anew, so that, in the course of twenty-four hours, the material secreted serves the same purpose again and again. During this repetition of secretion and absorption, it becomes little by little metamorphosed into other products, which are eliminated by the lungs and kidneys (Parkes, Murchison).

The functions of the bile so far as known are:

_a._ The solution of alimentary matters, and especially of fat, in the intestine, and the hastening of endosmosis, of fats and peptones;

_b._ The stimulation of peristalsis in the bowel;

_c._ Antisepsis and deodorization of the contents of the bowels;

_d._ The determination of the formation of glycogen;

_e._ The excretion of bile coloring matter, bile acids and cholesterine.

In regard to the glycogenic action it may be said that in cats, the bile ducts of which have been tied, no glycogen was formed, even when the diabetic puncture of the brain was made (Legg). Clinical observation seems to throw some doubt on the formation of bile coloring matter apart from the liver. In diseased liver with suspended secretion of bile (waxy and fatty degeneration, cancer, cirrhosis) the bile pigment was found in neither blood nor urine (Frerichs, Murchison, Haspell, Budd). Even after extirpation of the liver in frogs, neither biliary acid nor pigment could be found in the blood (Müller, Lehmann, Moleschott). These results must, however, be qualified by the observations of Hammersten who found bilirubin as a normal constituent of blood serum in the horse, and by Virchow’s discovery that hæmatoidin (now held to be identical with bilirubin) is constantly found in old blood extravasations into the tissues.

The origin of the bile coloring matters may be traced in part to destruction of red globules in the liver. Quincke has shown that in the hepatic capillaries in post-embryonic life the leucocytes englobe and destroy the old and worn out red blood corpuscles which thus become a source of bile coloring matter. Such destruction is specially likely to occur in badly maintained conditions of the blood, and in hepatitis or other liver disease in which the white cells accumulate in the hepatic capillaries, and when the blood current is retarded. Hence the liability to jaundice in such conditions. The formation of new red blood corpuscles has been observed in the protoplasmic cells of the liver in the embryo, but this has not been established for post-embryonic life (Neumann, Lowit).

The two common coloring matters of the bile are =bilirubin= which colors the yellow bile of man, omnivora, and carnivora and =biliverdin= which tints the dark green bile of herbivora. =Bilirubin= (C_{32}H_{36}N_{4}O_{6}) forms transparent fox red clinorhombic prisms. It is insoluble in water but soluble in chloroform, and may thus be separated from the biliverdin which is insoluble in chloroform. United as a second basic acid with alkalies it is soluble in water. It is easily obtained from the red gall-stones of man or ox, and is chemically identical with hæmatoidin. =Biliverdin= (C_{32}H_{36}N_{4}O_{8}) is an oxidized derivative of bilirubin and is insoluble in chloroform, slightly soluble in ether and freely soluble in water. In addition to its presence in bile it has been found in the placenta of the bitch. The =test= for bile coloring matter is made by placing a drop of the suspected liquid on a white porcelain plate and adding a drop of impure, brown, nitric acid (nitric and nitrous acids). If bile is present there is produced a beautiful play of colors passing from the green of biliverdin, through blue, violet, red, and ending in yellow.

With regard to the formation of bile pigments in morbid conditions it may be noted, that agents which dissolve the red blood globules (such as bile acids or water), when injected into the veins determine the appearance of bile pigment in the urine (Frerichs, Kuhne). When we consider that an animal (dog) secretes ¹⁄₅₀ of its body weight daily of bile, and that nearly all of this is re-absorbed from the intestines, we can realize this as an important source of bile and urinary pigments.

Of the =bile acids=, =taurocholic= is the most abundant in the bile of man, birds, and of many mammals and amphibians, while =glycocholic acid= is the more plentiful in the ox and pig. It is absent in sucklings. The taurocholic acid has been found to prove most destructive to red blood corpuscles, and in strong solution is distinctly antiseptic, checking the development of bacteria, of the alcoholic and lactic fermentations and of the tryptic and diastatic action of pancreatic juice.

These are conjugate acids, formed by the union of cholic acid with taurin and glycin respectively, and they are found almost exclusively, in combination with soda in the bile. They are found in the liver and do not accumulate in the blood when the liver has been removed. They increase under an albuminous diet.

The =test for bile acid=, is to take the suspected liquid from which all albumen has been precipitated, add a few drops of solution of cane sugar, shake into a froth, and pour sulphuric acid, drop by drop, down the side of the test tube. A _reddish purple_ color appears in the froth, and shows two absorption bands at E and F. Any albumen left in the liquid will give the same color, but only one absorption band.

The =secretion of bile= is more abundant on animal than on vegetable food, and on albuminous than fatty. It ceases during hunger, but is increased by ingestion of water. Its solids are most abundant one hour after feeding. It increases under a copious and rapid blood supply, but is arrested by diminished blood flow, even under increased pressure (in ligature of the vena cava in front of the diaphragm). Vigorous exertion, drawing off blood to the muscles of the trunk, diminishes the secretion of bile, while transfusion of blood, up to a given grade of blood pressure increases it. Nervous conditions, which cause contraction of the portal vessels, increase the secretion by forcing more blood through the liver. Such are strychnia or other stimulation of the valve of Vieussens, of the inferior cervical ganglion, of the hepatic or splanchnic nerves, or of the spinal cord. Fever causes its arrest.

The =secretion of bile= is further stimulated by the following :

_a._ The ingestion of bile into the stomach and abdomen. This being absorbed and carried to the liver greatly increases the biliary secretion. It is not necessary that the bile shall be a product of the same genus of animal, the bile of the ox is an active stimulant of the liver of the dog.

_b._ Of medicinal agents the following increase and liquefy the bile: olive oil in large doses, phosphate of soda, salol, and salicylate of soda.

_c._ The following not only increase the bile, but through their purgative operation, expel it from the bowels: calomel, mercuric chloride, colocynth, aloes, jalap, rhubarb, podophyllin, and cold rectal injections. These accordingly lessen the secretion later, by removing the stimulus of the absorbed bile.

_d._ The following are comparatively mild biliary stimulants: benzoic acid, benzoate of soda, oil of turpentine, terpene, terpinol, and euonymus, and still less active are alkaline bicarbonates, bromides, sulphates and chlorides, arsenic and ether.

=Secretion of bile is lessened= by: starvation, a too fatty dietary, alkaline iodides, atropia, strychina, hepatic degenerations, (fatty, cirrhosis), catarrh of the bile ducts, diseases of the liver, gall duct, or duodenum which interfere with the discharge of bile, the antisepsis of the bowels, or the reabsorption of bile. This work virtually moves in a vicious circle, as the action of septic ferments in the duodenum hinders the reabsorption of bile and of the food products which go to the production of bile, and in its turn the withholding of bile from the intestine removes the normal antiseptic (the bile acids) and favors septic fermentation and the inhibition of duodenal digestion and absorption. Another factor is found in the ptomaines and toxins absorbed from the alimentary canal and arrested in the liver. These debilitate the liver cells, impair the liver functions and lay the gland open to bacteridian infection. The bile in such a case is transformed into a pale or yellow, viscid liquid, with more or less dark colored granular debris, and this proves a favorable culture ground for bacteria especially the _golden staphylococcus_ and the _bacterium coli commune_. With septic condition of the liver the usual result of ligature of the bile duct is a peri- and intralobular sclerosis and the formation of minute biliary abscesses. In the absence of sepsis, ligature of the biliary duct, produces—not abscess but—necrobiosis, preceded by interlobular connective tissue hyperplasia, and granular or fatty degeneration of the hepatic cells. (Charcot, Legg, Lahousse, Dupre).

THE LIVER AS A DESTINATION AND DESTROYER OF POISONS.

The liver in the mature animal, being the one destination of the blood carried in the portal vein, necessarily becomes the recipient of all medicinal and poisonous agents absorbed by the capillaries and venous radicals of the stomach and intestines. This organ retains and lays up for a time the heavier metals, such as the salts of copper and iron, the iodides and bromides, the vegetable alkaloids such as nicotine, quinine, morphia, and curare, the toxic elements of the bile, the ptomaines and toxins produced by gastric and intestinal fermentations, indol, phenol, etc. Some agents it transforms, as peptones (which it renders non-poisonous), casein, the carbonate of ammonia and its salts with vegetable acids, also indol and phenol, which it combines with sulphuric acid as indyxol and phenyl sulphate, thus rendering them much less toxic. The destructions or new combinations established in the cases of the ptomaines and toxins may explain why such agents are usually much less poisonous when taken by the stomach than when generated in tissues or blood, or when injected hypodermically. Another interesting fact in connection with the ingestion of these bacteridian products (ptomaines and albumoses) is that, when the liver functions are normal as evidenced by the production of glycogen, the toxins are largely destroyed, and they fail to produce poisoning, whereas with a functionally deranged liver and no production of glycogen, they retain their potency, almost as if injected subcutem.

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, C_{6}H_{12}O_{6}) is undoubtedly formed in the stomach and intestines by the action of saliva and pancreatic juice on starch (C_{6}H_{10}O_{5}), and glucose and laevulose (C_{6}H_{12}O_{6}) are also derived from the transformation of cane sugar (C_{12}H_{12}O_{11}). 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.

GLYCOSURIA IN SOLIPEDS.

Heiss records two cases of this disease in heavy Belgian horses ten and eleven years old, the urine of which showed a percentage of 3.75 of grape sugar, and which died in two months in a state of marasmus. The liver was enlarged and of a clay yellow color. Dieckerhoff reports one fatal case in which there were also yellow discoloration, congestion and hypertrophy of the liver. No lesion could be found in the pancreas nor nervous system. Perosino records a case in a horse suffering from contagious adenitis, which may be supposed to have been connected with the action of the toxins or the imperfectly oxidized albuminoids on the nerve centres or liver. Delprato relates six cases in the same stable in overworked, half starved and emaciated horses. Rueff and Mouquet each contributes a case occurring in paraplegia attendant on hæmoglobinuria and in which the amounts of sugar were respectively 5.85 and 1.01 per cent. These latter cases are manifestly complicated ones in which the reflex irritation (or inhibition of glycogenesis) is transmitted from the diseased or poisoned brain to the already disordered liver.

_Symptoms._ There is a profound interference with nutrition, a rapid loss of flesh and weight, of spirit and energy and an extreme muscular weakness in spite of an excessive appetite. The subject is fatigued and breathless under the slightest exertion, the flanks are retracted and hollow, and the hair dry, rigid and lifeless. Appetite is poor and fastidious, but an intense and consuming thirst is usually present, the animal drinking deeply at every opportunity, and passing urine with corresponding frequency and abundance. The urine is clear, yellow, neutral, and saccharine, the sugar varying from 1 to 12 per cent. (3.6 on an average). Notwithstanding the amount passed (55 litres per day, Cadeac) the density usually exceeds the normal (1052 and upward), normal being 1040 to 1050. There may or may not be hyperthermia, and in exceptional cases appetite has been retained to the last. Cataract and corneal ulceration are sometimes observed as in man.

_Diagnosis._ Presumption may arise from the above mentioned symptoms, and especially the bulimia, the polydipsia, the polyuria, the rapidly advancing emaciation, weakness, and prostration and the ocular troubles, but conclusive evidence is only found in the presence of glucose permanently in the urine.

_Tests for Sugar in the Urine._ For one who can go through it the touching of the tip of the tongue with a drop of the suspected urine will give a prompt and reliable test.

_Fehling’s_ cupric test is the next best for simplicity and availability. Dissolve 34.639 grammes (1⅕ oz.) pure cupric sulphate in 200 cubic centimeters of distilled water: 173 grammes (6 ozs.) of pure neutral sodio-potassic tartrate and 80 grammes of potassium hydrate in 500 cubic centimetres of distilled water. Add the copper solution slowly to the potassium one and dilute the clear mixture to one litre. One cubic centimeter of this fluid will be discolorized by 0.005 gramme of sugar; or 200 grains will be discolorized by 1 grain of sugar.

_Trommer’s_ test is even simpler for a mere qualitative test. Pour the suspected urine, freed from albumen, into a test tube and add a solution of caustic potassa or soda until distinctly alkaline. Should this throw down earthy phosphates or carbonates filter these out. Then add drop by drop a solution of pure cupric sulphate in distilled water (3.5:100) so long as it throws down a yellowish red precipitate of oxide of copper. When the supernatent liquid remains clear and assumes a distinctly bluish tint, the sugar has all been precipitated. The amount of precipitate is a criterion of the quantity of sugar, which may be otherwise estimated by the amount of copper salt used.

_The fermentation test_ is made by adding a teaspoonful of liquid yeast to four ounces of the suspected urine, stopping the flask lightly and placing it in a temperature of 60° to 80° F. for 12 to 24 hours when the sugar will have been converted into alcohol and dioxide of carbon. The loss of weight will indicate the amount of sugar, as also will the lowering of the specific gravity. If before testing the urine was 1060, and after 1035, it contained 15 grains of sugar to the fluid ounce.

_Prognosis._ This is always rendered more grave in the horse than in man, because of the impossibility of putting him on a purely albuminous diet. The great tendency is to a rapidly fatal issue, especially in cases of irremediable structural lesions in the brain and liver. Where the disorder is largely functional, as in connection with hæmoglobinuria or as the result of poisons ingested the prospect of recovery is often good.

_Treatment._ In cases due to poisoning the use of antidotes and eliminating agents will be effectual, and in transient and curable diseases like pulmonary disorder, hæmoglobinuria and paralysis the appropriate treatment will restore. In the more inveterate or constitutional cases all treatment is liable to prove ineffectual. At the outset some apparent amelioration may be obtained from salicylic acid, salicylate of soda, bicarbonate, acetate, citrate, sulphate or chloride of soda, nitro-muriatic acid and other cholagogues. Blisters to the perichondrium may also be employed. Later, when degeneration of the liver has reached an extreme point, these will be of no avail. Cadeac recommends acetanilid, antipyrine, and benzo-naphthol largely on their antiseptic merits, and Jong claims a recovery in a horse under daily doses of 12 grains of codeine. Opium has long been employed in man with partially good results, and croton chloral, strychnia, phosphoric acid, iodoform and ergot are recommended in different cases.

One of the most beneficial agents is skim milk or buttermilk as an exclusive diet, and this may be to a large extent adopted for the horse. Under its use the sugar may entirely disappear, and though rheumatoid pains in the joints may be brought on, these usually subside on withdrawing the source of lactic acid. They may further be met by the use of salicylates. The greatest care should be taken of the general health, an open air life, with protection against colds and storms, and a healthy condition of bowels, kidneys and skin being particularly important.

The impaired digestion and assimilation usually demand carminatives, stomachics, bitters, and mineral acids, particularly the nitro-muriatic. With the same intent a fair amount of exercise short of absolute fatigue should be secured. But each case will require a special study and treatment consonant to its special attendant lesions, its causative functional disorders, and its stage. One case may demand attention to bacteridian poisoning, one to a better regimen and diet, one to liver disease, and one to disease of the brain, etc. After this treatment specially directed to the abnormal function or structure, would come the more specific treatment for mellituria which would be more or less applicable to the general glycolytic disorder.

GLYCOSURIA IN CATTLE.

Accompaniment of parturition fever and apoplexy. Essential glycosuria.
Dense saccharine urine, passed often, congested mucosæ, emaciation.
Lesions uncertain. In parturition fever and apoplexy the congested
medulla is the reasonable starting point. Toxic glycosuria. Treatment:
addressed to the primary disease or poison; otherwise treat as in the
horse.

In cattle this has been observed as a symptomatic affection in connection with parturition fever or apoplexy (Nocard, St. Cyr, Violet). One case of essential mellituria has been recorded by Darbas.

_Symptoms._ In the last mentioned case in a work ox, the animal, when at work, would stop every five or ten minutes to urinate, passing a small quantity of amber colored urine of a high density and containing a large amount of glucose. The conjunctiva was pink, the animal considerably emaciated, and rest and generous feeding brought about no improvement, so that the subject was finally sent to the butcher to anticipate a natural death.

The lesions in this case are altogether hypothetical. The red eyes might imply congestion of the encephalon (medulla), but the redness might be caused by active disease in the liver, pancreas or kidney. The failure to notice jaundice does not indicate a healthy liver, as some of the most fatal diseases of that organ are unattended by icterus. The frequent emission of urine in small amounts would imply irritation in kidneys or bladder, from which the glycogenic stimulus may have started. In the absence of any more definite evidence of disease in other organs it is, however, more probable that the fundamental disorder resided in the liver, the great glycogenic factor of the body.

In parturition fever, the presumption is in favor of considering the congested medulla as the starting point of the disease, yet in view of the manifest paralysis of stomach and bowels, it is not improbable that the vascular congestion and paralysis of the chylopoietic viscera constituted the initial step in the morbid process, while the glycogenesis was the result of a reflex operation on the liver.

Toxic mellituria would occur in cattle under the same conditions as in the horse.

_Treatment_ is only hopeful in the sympathetic and toxic forms. These must be treated according to the nature of the primary disease or the poison. To these the general principles of treatment as recommended for the horse should be superadded. For essential diabetes an exclusively milk diet and any one of the agents that have given good results in man or horse can be tried, but with an animal in fair condition it will be better as a rule to turn him over to the butcher.

GLYCOSURIA IN THE DOG.

More common than in horses and cattle. Causes: pampered in diet,
sweets, liver, disease of pituitary body, or mostly of the liver.
Removal of pancreas. Brain and nervous lesions and reflex action.
Symptoms: pampered asthmatic subject, with dysuria and lameness,
dense, saccharine urine, bulimia, loss of weight, corneal ulcers,
cataracts, palsy, coma. Duration: 4 to 8 months, sugar may disappear
with complete liver degeneration. Diagnosis: by pampered condition,
asthma, thirst, diuresis, later by loss of weight, troubles of vision,
saccharine urine. Lesions: usually hypertrophied, fatty or caseated
liver, thickened capsule, disease of thyroid, heart and eye.
Treatment: skim or butter milk as sole diet, restricted diet of lean
meat clear of fat, warmth, dryness, pure air, sunshine, gentle
exercise only, cholagogues, sodium sulphate, or chloride, or
carbonate, or salicylate, salol, nitro-muriatic acid, antithermics,
ergot, codeine, bitters, mineral acids, derivatives.

Among domestic animals the dog has furnished the greatest number of cases, yet even in this animal the disease appears to be far from common.

_Causes._ The relative frequency of diabetes in the dog is probably dependent on his life in human dwellings and on gourmandizing on dishes prepared for man. Friedberger and Fröhner have produced the disease artificially by feeding a great quantity of sugar and W. Williams has met the disease in dogs fed exclusively and generously on liver. Thiernesse records one case complicated by atrophy and steatosis of the pituitary body, but in all other instances the appreciable lesions were confined to the liver. In one case, reported by St. Cyr, the liver was hypertrophied, yellow, mottled, marked by irregular elevations of congested and hypertrophied hepatic tissue, and showing extensive degeneration—mucous, caseous and fatty. Thiernesse found the liver of a yellowish white color, and the seat of fatty degeneration implicating the hepatic cells. Franzenberg in one case found fatty degeneration of the liver, and Fröhner and Schindelki, in four cases, met with extensive hepatic disease. The macroscopic lesions of the disease in dogs as in horses appear to be mainly hepatic.

On the other hand the complete removal of the pancreas in the dog by Mering, Minkowski, Thiroloix, Lancereaux and others was invariably followed by mellituria, so that even in the absence of clinical examples, we must recognize pancreatic lesions and functional disorders as possible primary causative factors in glycosuria. In the light of experimental medicine we must similarly recognize brain and nervous lesions and reflex actions as possible causes, even if as yet unsupported by clinical facts observed in the dog.

_Symptoms._ The disease usually appears in an old, fat, pampered dog, affected with dyspnœa or asthma, with dysuria and lameness. The urine is high colored, viscid, and of a high density (1055 to 1060, the normal canine urine being about 1020), and charged with glucose. The subject may have an enormous appetite but fails to gain in weight, and after a time loses flesh and becomes badly emaciated. The pulse is small and frequent, and the temperature which at the outset may reach 102°, falls to the normal as the end approaches. Watering eyes, corneal ulcers, and cataracts as well as hemiplegia and diabetic coma may precede death. The amount of sugar has been found to vary in different cases from 3.2 to 12 per cent. of the urine.

_Course._ _Duration._ The dog may live from four to eight months and, as in the horse, sugar may finally entirely disappear from the urine, in connection with the progressive degeneration of the liver. If the patient is unable to take exercise, the case reaches a more speedily fatal issue.

_Diagnosis_ is deduced from the bulimia, pampered condition, breathlessness, thirst, and diuresis, the subsequent loss of condition, ocular troubles, and dropsy or coma, the whole being confirmed by the dense, high colored, viscous, saccharine urine.

_Lesions._ As already noticed the most constant lesion is hypertrophy of the liver, which is swollen unevenly, has thickened borders, is yellow or red, very friable and often fatty, or caseated. The capsule of Glisson is thickened and fibrous. Hypertrophy and fatty degeneration of the thyroid have been found in different cases and in one instance insufficiency of the mitral valve with systemic venous congestion. Ocular troubles are constant.

_Treatment._ Put the patient on an exclusive diet of skim or butter milk or if this is impossible it may be conjoined with lean meat—raw or cooked—keep warm and dry, but give plenty of open air and sunshine. Avoid fatigue and over exertion. Restricted diet is of great importance. During the siege of Paris the short rations led to the disappearance of glycosuria from many human patients.

Among medicinal agents, cholagogues come first, sulphate of soda with chloride of sodium, bicarbonate of soda, salicylate of soda, salol, nitro-muriatic acid, may be named. For the febrile condition, antipyrine, acetanilid, or phenacetin may be employed, and iodoform, ergot or codeine may be tried when other measures fail. Bitter tonics and mineral acids may be beneficial, and lastly blisters to the region of the liver may prove of service.

OBESITY AND EMACIATION.

Sugar essential to growth. Ratio of liver to active increase in
weight. Obesity and fatty degeneration. Small inactive liver and
stunted growth, or loss of weight. Biliary fistula, death in 12
months. Influence of pancreas. Nitrogenous food for obesity, outdoor
life, exercise, cholagogues, salines. Saccharine and starchy food for
emaciation, hepatic, and pancreatic stimulants. Mild laxatives and
cholagogues, pure air, green, succulent food, pure water, bitters,
tonics, moderate exercise.

There is reason to believe that both of these occur as results of hepatic disorder. The generation of sugar in connection with rapid cell growth in germinating seeds and growing plants, and also in rapidly growing animal tissues as in the body of the fœtus and fœtal membranes, and finally in the inflammatory products of pneumonia and in leucocytes, seems to imply that it is essential to such cell growth (Murchison). In keeping with this is the fact that the liver is of relatively much greater size in the fœtus and in the young and rapidly growing animal, and also in meat producing animals which have been selected and bred through many generations for early maturity and rapid fattening. The enormous development of adipose tissue and of lipomata in such animals is essentially abnormal, though it is a deviation from the natural that is esteemed as evidence of excellence, and a necessary condition of success in the meat producing industry. While other conditions are necessary to the production of such obesity, such as abundance of rest, slow, shallow breathing, a genial climate, and a generous hydro-carbonaceous food, yet all of these would prove ineffective without a large liver, working under high pressure in producing a large output of sugar. The mere obesity in the meat producing animal is not considered as disease and it is only when the tendency to fat production culminates in an adipose degeneration of the muscles and other tissues that actual disease is conceded.

_Emaciation_ in certain cases is traceable to the opposite condition. A small or inactive liver with a diminished production of sugar and fat will ensure loss of weight, which is still further aggravated by decreased secretion of bile and insufficient absorption of peptones. Experimentally this condition has been repeatedly brought about by making a biliary fistula, and cutting off all bile from the intestine. Death preceded by extreme emaciation ensues in 12 months (Murchison). This being the case with the escape of all the bile secreted, a slower but no less certain emaciation must follow on a structural or functional disorder of the liver which is attended with a greatly lessened production of bile. This, indeed, is the condition met with in advanced glycosuria, when the liver is the seat of general fatty degeneration.

From the experiment of the removal of the pancreas we may infer that diseases of this organ which pervert or destroy its normal functions, will check glycogenesis in the liver by withholding the supposed pancreatic ferment, and by so doing will conduce to emaciation and marasmus.

So far as obesity and emaciation are dependent on diet they may be checked by subjecting the patient to the dietary which will favor a more healthy liver function. For excessive _obesity_ a strictly nitrogenous food in restricted amount will tend to lessen the glycolytic action of the liver and secure the formation of muscle rather than fat. An outdoor life, and an active though not exhaustive use of the muscles will greatly favor this result. For the carnivora or omnivora a diet of lean meat or skim milk might be employed, while for the herbivora, wheat bran, cotton seed hulls, beans, peas, vetches, or cotton seed would measureably meet the demand. Cholagogues and saline laxatives, by eliminating from the liver and intestine, will contribute to the same end.

If _emaciation_ depends on a deficiency of sugar, that may be freely fed along with richly amylaceous food, and the liver may be stimulated to increased glycogenesis, by stimulants such as chloroform, ammonia, or ether, and by a moderate use of carbonate of soda or other alkalies. Ether has in addition a stimulating effect on the pancreas and will tend to increase that ferment which stimulates the liver to its glycogenic work. Mild laxatives and cholagogues will second this, such as small doses of podophyllin, taraxacum, nitro-muriatic acid, chloride or bromide of ammonium, plenty of pure air, abundance of green or aqueous food, and plenty of pure drinking water. Finally moderate exercise, by increasing the aspiratory action of the chest and thereby accelerating the hepatic circulation is a material stimulant of the glycolytic function. Bitter and other tonics are contributions to the same object and should not be neglected.

SECONDARY OR REMOTE RESULTS OF LIVER DISEASE.

In gout: Arrest of oxidation of proteids into urea. Deposits of
biurate of lime on joints, and other disorders. Urinary calculi
containing urates, cystine, xanthine, etc., also from imperfect
oxidation of albuminoids. Oxalic acid represents a similar arrest.
Kidney degenerations from irritating urates and oxalates. Fatty kidney
from excessive glycogenesis. Digestive disorders from excess or
deficiency of bile or torpid liver. Nervous disorders, dullness,
lameness, vertigo, spasms, irritability from hepatic inactivity and
resulting poisons. Sore throat and bronchitis from hepatic
derangement. Skin eruptions in tardy or imperfect action of the liver.
Treatment: Abundant water, succulent vegetables, ensilage, fresh
grains, balanced ration, in carnivora and omnivora oat meal,
buttermilk, clear meat juice, avoid sweets, gravies, spiced animal
food. Dangers for pampered horses, dogs, and old improved meat
producing animals. Open air exercise. Laxatives with alkalies,
salines, mercurous and mercuric chloride, pilocarpin, chlorides,
iodides, bromides, nitro-muriatic acid, ipecacuan, euonymus, bitters.

Among the many secondary results of hepatic disorder, and which are habitually described as affections of other organs a few may be mentioned as indicating the wide range of influence exercised by the liver in disease as well as in health.

_Gout_ as it appears in fowls and omnivora is directly due to the arrest of the transformation of the albuminoids into urea. Circulating in the system in the form of the less perfectly oxidized and less soluble uric acid, it determines deposits of biurate of lime around the joints, with local inflammations, and disorders of circulation and innervation, and altered spirit, temper, etc.

_Urinary calculi_ in the same animals, are composed largely of urate of lime, cystine, xanthine and other nitrogenous products representing various stages of oxidation short of the final transition into urea and ammonia. Recognizing the active rôle which the urinary bacteria fill in this respect we must still acknowledge the great importance, as causative agents, of an excess in the urine of these comparatively insoluble products.

The oxalic acid found in certain calculi points in the same direction, as this acid, both in the body and in the laboratory, is found to result from the oxidation of uric acid (Wohler, Schenck, Hutchinson).