By fever is generally understood a complex of phenomena the dominant characteristic of which is a rise of body temperature. If the term "fever" be confined simply to the latter aspect, one might classify fevers as follows:

(1) Physiologic fever, induced, for example, by immersion in a hot bath at a temperature of 400, which prevents the normal loss of body heat through radiation and conduction. (2) Neurogenic fever, as brought about by the direct stimulation of nerve-cells in the corpora striata of the mid-brain. (3) Non-infective surgical fever, commonly called aseptic fever, due to the resolution of blood-cells or crushed tissue in the organism. (4) Infective fever, produced after the infection of the organism by certain bacteria or their products and by some protozoa. Or one may consider fever as being due to infection by bacteria or protozoa, and include all other increases of temperature under the term of hyperthermia.

In a previous chapter the mechanism of normal heat regulation has been explained. It was there noted that on a warm, moist day the temperature of a fat individual, when he was working hard, rose considerably above the normal. This effect, if carried to an extreme, results in sunstroke, in which the overheating of the body causes a rapid pulse, accompanied by dizziness, delirium, or unconsciousness. But in the great majority of cases the body temperature remains delicately balanced, notwithstanding changes in outside environment, or internal heat production. In the fat person at hard work the condition of increased metabolism is combined with that of difficult discharge of heat. A person placed in a bath at 400 would be subject to conditions where there could be no heat loss, but rather a gain in heat, even though his metabolism were low. In a normal person, therefore, a rise in temperature may be due to increased heat production, with difficulty in discharging it, or a check of heat loss may be the only factor of the higher temperature. In the discussion of fever one must consider two possible causes: (1) an increase in heat production, and (2) a decrease in the facilities for the discharge of heat produced.

It has already been set forth that the metabolism in a coldblooded animal increases with the temperature of his environment. Warmed tissue metabolizes more material than cooled tissue. It is therefore to be expected that the metabolism in an organism which has been warmed to fever heat will be greater than the normal. This was beautifully shown in the experiments of Pfluger,1 who subjected both curarized and normal rabbits to external warmth which raised their temperatures. In the animals whose voluntary muscles were paralyzed by curare as the rectal temperature rose from 30° to 410 the oxygen absorption increased 10 per cent, for each degree of temperature increase. In the normal animals the increased metabolism between temperatures of 38.6° and 40.60 was shown by increases of 5.7 per cent, for oxygen and 6.8 per cent, for carbon dioxid for a rise of 1° of temperature.

It has been noted in another chapter (p. 144) that Rubner found in man that a bath at a temperature of 350 had no effect on metabolism, while one at 440 increased the volume of respiration 18.8 per cent., the oxygen absorption 17.3 per cent., and the carbon dioxid elimination 32.1 per cent. Linser and Schmid2 confirm these results in experiments on two men suffering from ichthyosis hystrix, which involved almost complete loss of function of the sweat-glands. The body temperature of these men could be varied by altering the temperature of their living-room between 300 and 380. The humidity of the room was from 40 to 50 per cent. The maximum increase in the metabolism of these individuals is represented by a rise in carbon dioxid excretion from 3.8 c.c. per minute and kilogram at the body temperature of 36.20 to 5.3 c.c. per minute and kilogram at 30°. The number of respirations, which were from 12 to 15 per minute at 360, increased to 20 and 22 at 39°. The total increase in the carbon dioxid output, due to a rise of 30 through simple warming of cells, amounted to 40 per cent.

1 Pfluger: "Pfluger's Archiv," 1878, xviii, 303, 356.

2 Linser and Schmid: "Deutsches Archiv fur klinische Medizin," 1904, lxxix, 514.

The next question is of the nature of the materials which are oxidized. It has long been known that urea excretion is abnormally high in fever,1 and this led to the inquiry whether the rise was merely the result of increased body temperature or was due to toxic influences.

F. Voit2 found that on artificially raising the temperature of a fasting dog to 400 or 410 for a period of twelve hours there was an increase in nitrogen elimination of 37 per cent, above the normal. Warming for a period of only three hours had slight effect. If, however, the animal were fed with meat and fat, warming increased the protein metabolism only 4 per cent. If the animal were given 30 to 40 grams of cane-sugar no increased metabolism of protein followed the rise in temperature to 410. It is apparent that the ingestion of protein and carbohydrates may control this rise in protein destruction due to a febrile temperature. F. Voit explains the increase in protein metabolism in hyperthermia as due to the quick combustion of glycogen and the consequent impoverishment of the tissues as regards carbohydrate material. Protein or carbohydrate ingesta furnish the necessary carbohydrate and prevent the hyperthermal rise in protein metabolism.

1 Traube and Jochmann: "Deutsche Klinik," 1855, vii, 511.

2 Voit, F.: "Sitzungsberichte der Gesellschaft fur Morphologie und Physiologic," 1895, Heft ii, p. 120.