Part 71

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).