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9970

VOL. II

FEB 201908

The Ohio State Medical Journal

JULY 15, 1906

No. 1

ORIGINAL ARTICLES

AUTO-INTOXICATION FROM THE GASTRO-INTESTINAL TRACT.*

HISTORICAL VIEWS CONCERNING THIS SUBJECT TRUTH AND ERROR CONCERNING THE THEORIES OF AUTO-IN

TOXICATIONS.

BY JOHN C. HEMMETER, M. D., PH. D., LL. D. Professor of Physiology and Clinical Medicine, University of Maryland, Baltimore, Md.

[Address on Medicine before the sixty-first annual meeting of the Ohio State Medical Association, May 9 to 11, 1906, Canton, Ohio.]

PRE-GALENIC MEDICINE.

Our conceptions and the doctrines which we have formulated concerning the nature of diseases, have undergone manifold changes during the past century. Before the era of bacteriology the doctrine which seemed to have the firmest hold upon medical thinking was the ancient theory of the Dyscrasias. We see traces of this hypothesis in the writings of Hippocrates. The real significance of the term was a depraved or abnormal state of the blood. The entire pre-Galenic medicine might be said to be comprised in the achievements of Hippocrates, Diokles, Herophilos, Erasistratos.

THEORY OF POISONOUS HUMORS.

One of the principal achievements of Galen was the construction of the thinking of those four great classical physicians into a system, and this system culminated into the doctrine of the Dyscrasias. Among the

last of the more modern representatives of this ancient doctrine was Rokitansky. The principal idea underlying the whole conception was that the juices of the body, particularly the blood, could undergo such changes that it contained poisonous humors; we could call them toxic substances, to the agencies of which the various diseases were due.

ERA OF BACTERLOLOGY.

About fifty years ago, Virchow's genius gave the deathblow to this so-called humoral pathology. Then gradually developed the era of bacteriology, in which the morphologic study of the bacteria and other living disease producers occupied the interests of medical workers. Recently bacteriology has arrived at a critical parting of ways, one of these leads to the doctrine of the disease toxins or chemical poisons derived from the cells of the organism itself, substances which the living body produces during its own life processes—and these are the auto-intoxications proper.

TRUE AUTO-INTOXICATIONS.

When toxic substances are produced in the internal laboratories of the body, but by living organisms introduced from the outside, these cannot strictly be classed among the auto-toxic substances. Thus diphtheria and tetanus and their toxins cannot logically be classed among the auto-intoxications; for it is not the cells of the organism which produce the poison in this case; but uræmia, eclampsia, gout and diabetic coma are true auto-intoxications.

* In the preparation of this address I have drawn largely from articles published by me in my Text-books on DISEASES OF THE STOMACH and INTESTINES in the "INTERNATIONAL CLINICS," Vol. II, 12th Series, in the ARCHIV f. VERDAUUNGSKRANKHEITEN," and other German and American journals.

NATURE AND CONCEPT. The history of medicine is extensively a history of studies and inquiries into the origin of disease. The processes which have been recognized as inducing disease have been relegated to four types. These pathogenic processes are named in the order of their importance: (1) Infections; (2) disturbances in nerve reaction; (3) disturbances in nutrition; (4) primary elementary dystrophies. More and more the agency of infection has encroached upon the domain of the other three pathogenic factors. At the present day the truths that are known or believed to be known concerning infection, do not suffice to explain the origin of disease; not only of disease in general, but we are unable in each and every case to explain the origin even of such diseases which we have many good reasons to believe are infectious in origin.

At the beginning of the nineteenth century the ancient views of humoral pathology and the doctrines of dyscrasias still occupied the medical mind. The endogenous causes of disease were thought to be abnormal compositions of the blood, secretions and tissue juices. As this view was gradually replaced by investigations based upon the natural sciences, pathology acquired a more exact and precise foundation. The evolution of cellular pathology brought with it the development of the chemistry of the cell, that is, of the chemic physiology and pathology. Even later, when bacteriology, the most recent daughter of cellular pathology, arose and seemed to absorb the doctrines of its mother science, cellular chemistry asserted its rights. In the search for the origin of the disease by the aid of modern cellular pathology and bacteriology, the chemical nature of the "materies morbi" could not be pushed to the background.

It required several decades before the technique and rough foundations of bacteri

ology were happily surmounted. But even during this time Pasteur repeatedly emphasized that the material which is essential to the existence of even an infectious disease is of a chemical nature.

Organic cell life is comparable to a chemical factory. ical factory. From introduced raw materials it manufactures those substances which are required for the maintenance of the organism. These are incorporated in the tissue juices and protoplasm. During the process of cell life and the performance of all functions, waste products are formed; these are excreted and removed from the cell body and eventually from the organism. Intake and output, assimilation and growth, destruction and breakdown of protoplasm by function-anabolism and catabolism-these terms comprise the life history of the cell. But all these processes, although inseparably connected with the morphological elements of the cell, are in their innermost nature nevertheless chemical processes. Even the life and activity of the bacteria must be considered in the light of chemical processes. The bacteria, per se, may cause an infection; they may produce primary metastatic foci of disease also, but these disease foci are as a rule local, for the general disseminated phenomena of these diseases are always caused by toxic metabolic products of the bacteria. These may originate within the body of the bacteria themselves, or they may be produced from the constituents of the animal cells in

and upon which the bacteria are parasitic.

In modern medical literature we find a superabundance of publications directed toward the recognition of external causes When one sifts the result of disease. gained thereby, one cannot fail to be impressed with the fact that they, by no means, suffice to explain the origin of many diseases. After all, the facts of etiology, derived from a study of infection, disturbances in nerve reaction, disturbances in

nutrition and of primary elementary dystrophies have been brought together, a large number of diseases remain for which no satisfactory explanation as to their origin has been offered. The so-called external causes of disease are particularly insufficient to explain those pathogenic disturbances which arise from some internal detriment or abnormal change. At this point we begin to seek the cause of the disease within the cell itself.

DEFINITION OF AUTO-INTOXICATION. Auto-intoxications, in the strict sense, are morbid conditions which originate by the agency of toxic products of metabolism in the organism itself, and in the etiology of which the direct activity of micro-organisms can be excluded. Among the safe examples of such auto-intoxication we can classify only such endogenous diseases of which the etiologic poison or toxine is known. A knowledge of these toxines is the sine qua non for the existence of an auto-intoxication. Strictly speaking, therefore, there are only three conditions which can logically be considered auto-intoxications. These are (1) ammonemia, the supersaturation of the blood with carbonate of ammonia, which is formed from urea, according to Treitz, within the intestinal canal and is absorbed into the circulation; (2) hydrothionemia, which is the absorption of sulphuretted hydrogen (HS) from the intestine, and (3) diabetic coma, which is most probably produced by the formation of beta-oxy-butyric acid, in the course of diabetes mellitus. With a little stretch of the imagination, three abnormalities of metabolism may be included which do not run their course with intoxication symptoms of the general organism. These are cystinuria, alcaptonuria and oxaluria. my opinion these conditions cannot be considered as independent diseases peculiar to themselves. Not one of them can, in the

In

present light of our knowledge, be considered a disease sui generis. Von Jaksch ("Die Vergiftungen," in Nothnagel's Spec. Path. u. Ther., Bd 1) would include under the auto-intoxications also acetonemia and uricacidemia (I c., p. 624). Under the heading of uricacidemia he makes the statement that there are diseases in which the most prominent phenomenon is the occurrence of increased quantities of uric acid in the blood, as well as in the urine. This statement, that uric acid occurs in the blood, is no doubt a lapsus linguae, for in none of the literature quoted by von Jaksch, nor in other literature known to me, is a satisfactory evidence given that uric acid, as such, occurs in the blood. This lack of preciseness of von Jaksch has no doubt been partially the cause of the widespread error that uric acid occurs in the blood as such. What this celebrated clinical chemist evidently intended to say was that uric acid occurs in the blood in certain diseases in the form of sodium bi-urate or quadri-urate.

SIGNIFICANCE OF THE DOCTRINES OF GASTRO-INTESTINAL AUTO-INTOXICATION. In order to establish the existence of an intestinal auto-intoxication, we have a right to demand two clinical proofs: (1) The demonstration of the poison or toxine itself; (2) the demonstration that the locality of its formation is in the gastro-intestinal tract. Unfortunately these two requisites have not been supplied in a great many of the diseases which Bouchard, the originator of the doctrine of auto-intoxication, classes among these abnormalities. The evidence furnished by Bouchard and others in support of their doctrine may be separated into experimental and clinical evidences.

CRITICISM OF THE EXPERIMENTAL EVIDENCES.-I have already stated that the doctrine of auto-intoxication, in order to

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