Under these conditions the heat production may be increased 30 or 40 per cent, above the normal, despite the characteristic cachexia.3 In milder cases of carcinoma, however, an increase in metabolism is not apparent.4

As regards tuberculosis May5 writes: "Larger quantities of the toxins produce, with certain exceptions, a direct injury to the cell protoplasm. They are strongly toxic. The quantity of protein destruction attributable to this cause is not very large and becomes of importance only when continued for a long period of time and where there is no compensatory regeneration. It appears that the power to regenerate on the part of these cells which are destroyed by toxins is greatly reduced and in severe cases entirely lost".

1 Krehl: "Pathologische Physiologie," 1904, p. 452.

2 Muller, F.: "Zeitschrift fur klinische Medizin," 1889, xvi, 496.

3 Wallersteiner: "Deutsches Archiv fur klinische Medizin," 1914, cxvi, 145. 4 Magnus-Levy: "Zeitschrift fur klinische Medizin," 1906, lx, 177.

5 May: Ott's "ChemischePathologiederTuberculc.se," Berlin, 1903, p. 335.

Other fevers show a high toxic destruction of protein. F. Muller1 reports a daily loss of 10.8 grams of nitrogen (equal to 318 grams of muscle) by a typhoid patient during eight days of fever when the daily food contained 8.3 grams of protein nitrogen and about 1000 calories. Administration of antipy-rin which lowered the body temperature somewhat lessened the protein destruction. During fever in Croupous pneumonia the protein metabolism is much higher than normal. After the crisis there is still a large excretion of nitrogen in the urine which continues until the croupous exudate has been decomposed by autolysis, absorbed by the blood, and metabolized in the body (epicritical nitrogen elimination). In acute pneumonic phthisis (galloping consumption), with its caseous transformation of lung tissue, there is a very high waste of tissue protein. F. Muller2 has shown that while the croupous exudate readily undergoes autolysis at a temperature of 400, with the production of deutero-albumoses, lysin, leucin, tyrosin, etc., the caseous mass does not undergo autolysis, although it permits free diffusion of soluble material, such as phosphates. Hence, although the protein of the cheesy mass is insoluble in the organism, the soluble toxins may be absorbed from the diseased part, and be the causative agent of the rapid destruction of body protein in galloping consumption.

The toxic destruction of protein in infective fever was definitely established by Kocher,3 who found that after giving to a typhoid patient a diet containing carbohydrate in large amount and containing very little protein it was absolutely impossible during the febrile period to reduce the output of urinary nitrogen to that corresponding to the low level of the normal "wear and tear" quota of protein metabolism. With the decrease in the intensity of the febrile process the loss of body nitrogen gradually diminished. This appears in the following table:

1 Muller, F.: "Centralblatt fur klinische Medizin," 1884, v, 569. 2 Muller, F.: "Verhandlungen des 20 ten Congresses fur innere Medizin," 1902, section iv, p. 192.

3 Kocher: "Deutsches Archiv fur klinische Medizin," 1914, cxv, 106.

Protein Metabolism In Typhoid Fever

Weight, 57.5 to 59.8 kgm.

Daily creatinin reduced from 2.5 to 1.5 grams.

Although the nitrogen in the urine of a normal man when this diet is given ranges between 2.5 to 4 grams, during the febrile period of this typhoid patient it averaged 16 grams and even reached 20 grams per day. Creatinin, uric acid, sulphur, and phosphorus elimination were increased during the febrile period, but declined with the decline in protein metabolism. Coleman and DuBois1 gave to typhoid patients diets which contained much larger quantities of protein (as much as 16 grams of nitrogen daily), but they were unable to obtain nitrogen equilibrium, even though the diet was rich in carbohydrate. The following table gives a summary of their data:

1 Coleman and DuBois: "Archives of Internal Medicine," 1915, xv, 887.

Chart Showing Negative Nitrogen Balances In Typhoid Patients Who Receive Food Calories In Excess Of Calculated Heat Production. Results Are Averages Per Day

Coleman and DuBois conclude that, though there was ample protein in the diet to establish nitrogen equilibrium in the normal man, it could not accomplish this in typhoid fever. It was impossible to escape the conclusion that the destruction of protein is caused by the toxins of the disease. In some cases the protein destruction continued several days after the body temperature had reached a low level.

In all fevers the septic products act upon the hunger centers in the brain, and appetite is wanting. This is evidenced throughout the course of tuberculosis, for example, and tends in this case to weaken the body's resistance through undernutrition. Forced feeding is therefore resorted to.

The experiments of von Hosslin1 strongly affirmed the beneficence of a liberal diet in ordinary fevers. He writes: "The results show that febrile patients, or at least those who do not run temperatures above 400 to 40.50, can digest and absorb the total amount of protein, fat, and carbohydrates which can be given them with their diminished appetite, provided the food is administered in a proper form. Temperature and metabolism are only slightly increased thereby".

1von Hosslin: "Virchow's Archiv," 1882, lxxxix, 317.