The great similarity of the numerous toxic agents described in Part II with the better known poisons warrants one in making analogies which suggest that they too are capable of causing tissue changes, inflammation, and, if the poisons are concentrated or their action persists for a long time, gross pathological lesions. It is in the kidneys that many poisons are separated and excreted. Strychnin, arsenic, lead, potassium chromate, phosphorous, cantharidin and the toxins of scarlet fever and diphtheria are all eliminated in the urine and all may produce true nephritis. Indeed the toxic origin of nephritis is so universally acknowledged that we need only discuss those arguments which show that it may be autogenetic. Applying the side-chain theory already described to nephritis, Vaughan would let the constitution symbol of the benzene ring with its six sides represent the kidney cell, and terms as a nephro-lysin any substance that will separate or split off a CH radicle.

Focal precipitations of uric acid and its salts are frequently found in the cells, interstitial tissue and tubules of the kidney, having been deposited there by precipitation from the cell secretion from the action of some precipitant acting as already described.

This recalls the crystalline deposits so frequently met with in the examination of vegetable tissues, the salts entering the cells in solution and becoming there precipitated by the specific secretion of the part or by some adventitious chemical substance. As will be shown in discussing acid intoxications, the auto-toxins cause such precipitations.

We must again refer to the experimental data given in Part II in arguing the intrinsic origin of nephritis, a disease which of itself is a primary cause of autointoxication. Adenin, one of the most poisonous of the purin bodies and one which is quite frequently formed, seems to have a peculiar selective affinity for renal tissue and in small doses causes nephritis with albumin, casts and spheroliths of uric acid in the urine, the latter occurring also in the renal cortex. Ethylene diamin, which we know is found in the liquids of the stomach in gastrectasis, is capable of producing nephritis even when given in very small doses. In order to show that hypoxanthin is capable of producing renal changes, Kolisch (20) administered it to rabbits and guinea pigs for periods of one and two months and found that parenchymatous degeneration was caused.

Butyric acid is known to cause nephritis, and for that reason it is not to be employed as a medicine.

In experiments upon animals in which intestinal obstruction was Caused, it was observed that degenerative changes had begun in the kidneys as the result of the cholin and other poisonous bases elaborated.

Gerontin is occasionally observed in crystalline form in the cells and nuclei of the liver and kidneys. In experimental poisonings with methyl guanidin the kidneys are found to be congested and the blood vessels injected, and as experimentation with this class of substances is continued, we may expect to find that other of these poisons, which we know cause degenerations of the neurons, cell metamorphoses, and the precipitation of acid salts, are quite capable of irritating the renal tissue and of producing nephritis.

From these few illustrations it is seen that we have positive evidence that nephritis may be of intrinsic origin. For clinical evidence shows these substances to be formed in various states, - experiment shows that they produce definite pathological changes which necessarily become a part of their toxicology.

Both nephritis and glycosuria may be dependent upon hepatic insufficiency. Ducamp (21) has shown the interdependence and co-operation of hepatic and renal functions, and that failure in one of them induces changes in the other. Suspension of the functional activity of the liver results in a diminution of urea with consequent lack of diuretic action on the renal epithelium. And in this way almost complete anuria may result, a thing which may be relieved by the administration of urea. In this way a circulais viciosus may be formed, the deficiency in liver action decreasing the urea, this in turn causing suppression of the urinary excretion, and thus a true intoxication with its poisoning of the entire system.

The importance of proper functional activity of the kidneys in the specific infectious diseases and where there are other extraneous poisons to be eliminated from the system, cannot be overestimated. In such cases the kidneys have added duties to perform and must eliminate not only the normal poisons of the body but also the bacterial toxins of the specific affection. Many of these toxins are capable of producing nephritis, which would greatly increase the gravity of the case, adding to it the possibility of uremia and intoxication from the metabolic end-products. Examples of this are frequently seen during or after scarlet fever or diphtheria the toxins of which cause nephritis, and the organism, unable to eliminate both its own poisons and those of the pathogenic bacteria, soon succumbs if elimination is not re-established or the poisons neutralized.

A specific instance of the importance of permeable kidneys is reported by Brouardel (19) in which several persons who had partaken freely of turkey were made violently ill with pronounced gastro intestinal symptoms. Of these persons but one died, and the post-mortem examination showed a substance resembling coniine in the viscera, this also appearing in the fowl. Defective kidneys were also found, which would indicate that faulty elimination of the ingested poison was the cause of death. Haines (19) urges the importance of renal disease as a cause of sudden death, not only from pausing uremia but also from failure to eliminate special poisons which might occur accidentally or in intercurrent digestive disorders.

Clinically it is frequently observed that renal disease is helped by measures which assist nutrition and digestion. The writer has observed a number of cases in which the use of strychnia in small doses has been followed by disappearance of myalgia, headache, swelling of the extremities, high tension pulse and many subjective symptoms, as well as disappearance of casts and albumin from the urine. Brunton in 1877 found that cases of albuminuria were often helped by the use of arsenic, the albumin vanishing while the drug was employed and returning when it was discontinued, and the writer has observed the same thing in five cases. As these drugs have no specific influence over the renal epithelium, blood pressure or circulation, it may be assumed that they reach the underlying condition of incomplete oxidation and thus prevent the formation of renal irritants.