A corroborating fact found by Shibata1 is that, although the amount of fat in the liver is increased in phosphorus-poisoning, the quantity of total fat in the organism is much reduced during the progress of this disease. In cases of fatty infiltration (so-called degeneration) Czyhlarz and Fuchs2 could find no evidence of an abnormally changed relationship between the quantities of cholesterol and fat present in the diseased tissue.

Medical literature was formerly greatly influenced by the idea of a reduced general oxidation in the body. Except in the case of myxedema which is accompanied by a fall in body temperature, and in some cases of obesity, no such condition occurs. The writer3 has shown that in phosphorus-poisoning, the classical example of supposed reduced oxidation, there was actually no reduction in the total heat production, but rather an increase. From the fourth day to the sixth of simple fasting in one dog the total metabolism for twenty-four hours averaged 45.2 calories per kilogram, and on the ninth day to the eleventh of fasting which preceded death from phosphorus-poisoning the heat production was 48.8 calories. These results have been confirmed by Hirz.4

It is therefore evident that the presence of lactic acid is only a symptom in the group of diseases just mentioned (p. 489), and is no more an indication of a reduction in oxidative power as represented by the total heat production than is the elimination of sugar in diabetes. The abundant ammonia in the urine is used to neutralize the acid produced. The reduction in the amount of lactic acid oxidized raises the total protein metabolism. The deficient deamination which results in the elimination of amino-acids in the urine may possibly be due to the injury of deaminating enzymes by the presence of lactic acid.

1 Shibata: "Biochemische Zeitschrift," 1911, xxxvii, 345.

2 Czyhlarz and Fuchs: Ibid., 1914, lxii, 131.

3 Lusk: "American Journal of Physiology," 1907, xix, 461.

4 Hirz: "Zeitschrift fur Biologie," 1913, lx, 187.

It has been stated that the action of phosphorus is to induce autolysis (self-digestion) of the body's protoplasm (Jacoby,1 Waldvogel2), since leucin, tyrosin, glycocoll,3 phenyl-alanin and arginin,4 and other amino-acids may be eliminated in considerable quantity in the urine. Wakeman5 finds a change in the relative amounts of histidin, arginin, and lysin contained in the liver substance after phosphorus-poisoning, arginin in particular being reduced below the quantity found in the liver of the normal dog. Oswald6 thinks that phosphorus destroys or weakens the anti-autolytic agents of the body. That autolytic enzymes do not gain free control over the cells through the direct influence of phosphorus is proved by the work of Ray, McDermott, and Lusk.7 These authors found that phosphorus injections raised the protein metabolism of fasting dogs to 250, 260, 283, 248, 183, and 164 per cent, of that of the dog when normal. They contrasted this increased protein metabolism with that obtained in phlorhizin glycosuria, which is represented by increases to 540, 450, 340, and 340 per cent. When, however, they gave phlorhizin and obtained the increased metabolism, and then injected phosphorus, this was not followed by any marked increase in protein metabolism. Under these circumstances phlorhizin glycosuria is the predominating factor, removing the glucose produced from protein before it could be converted into lactic acid.

1 Jacoby: "Zeitschrift fur Physiologische Chemie," 1900, xxx, 174.

2 Waldvogel: "Deutsches Archiv fur klinische Medizin," 1905, lxxxii, 437.

3 Abderhalden and Bergell: "Zeitschrift fur physiologische Chemie," 1903, xxxix, 464.

4 Wolgemuth: Ibid., 1905, xliv, 74.

5 Wakeman: Ibid., 1905, xliv, 335.

6Oswald: "Biochemisches Centralblatt," 1905, iii, 365.

7 Ray, McDermott, and Lusk: "American Journal of Physiology," 1809, iii, 139.

Analogous to this is the observation of Sass,1 who found that under normal conditions strychnin convulsions reduced the titratible alkalinity of the blood on account of the formation of lactic acid, but in depancreatinized dogs this result could not be achieved because lactic acid could not be produced from glucose.

As regards phosphorus-poisoning Araki2 believes that lactic acid accumulation is due to lack of oxygenation of the tissues caused by a slow heart-beat, but not due to anemia. He does not believe the oxygen deprivation to be very pronounced. The writer offers the explanation that phosphorus may affect the conditions which lead to the oxidation of the lactic acid derived from glucose (see p. 263), and the accumulation of this acid may prevent the action of some of the deaminating enzymes; and, further, its non-combustion may necessitate an increase of protein metabolism.

This theory is strengthened by the discovery of Schryver3 that the addition of lactic acid favors the accumulation of amino-acids in autolysis of the liver.

Claude Bernard showed that glucose, whether derived from protein or starch, was convertible into glycogen, and this again was changeable into glucose. Present knowledge adds lactic acid to both ends of this chain in showing the following possible progression - lactic acid, glucose, glycogen, glucose, lactic acid (see p. 263).

Quite pertinent to this theoretic discussion is the observation of von Jaksch4 on a patient who recovered from phosphorus-poisoning, and in whom a desire for carbohydrates marked the beginning of convalescence.

It should also be noted that more carbohydrates must be ingested in cases of hepatic disease to maintain nitrogen equilibrium than are required in health.6

1 Sass: "Zeitschrift fur ex. Path, und Ther.," 1914, xv, 370.

2 Araki: "Zeitschrift fur physiologische Chemie," 1893, xvii, 337. 3 Schryver: "The Bio-Chemical Journal," 1906, i, 153.

4 von Jaksch: "Zeitschrift fur physiologische Chemie," 1903, xl, 123. 5 Tallqvist: "Archiv fur Hygiene," 1908, lxv, 39.

A curious anomaly of carbohydrate metabolism has been discovered by Underhill1 following the administration of hy-drazin, which he defines as a poison with an almost specific effect upon the cytoplasm of the parenchymatous cells of the liver. It attacks first the cells in the center of the lobules, while phosphorus shows its first effects upon the cells of the periphery. .If 50 milligrams of hydrazin per kilogram of animal be given to dogs, the quantity of glucose in the blood and of glycogen in the liver is greatly reduced and the administration of glucose may cause the death of the animal within twelve hours. Otherwise the dog recovers in five days. Underhill and Murlin2 found that the administration of hydrazin to fasting dogs increased the respiratory quotient. An increased oxidation of carbohydrate, therefore, probably explains the diminished blood-sugar content and the disappearance of glycogen from both liver and muscles. Hydrazin was without influence upon the level of the basal metabolism.

1 Underhill: "Journal of Biological Chemistry," 1911-12, x, 159. 2 Underhill and Murlin: Ibid., 1915, xxii, 499.