A study of the physiology of pepsinogen in the human with special reference to its disturbance in diseases of the upper gastro-intestinal tract

Abstract

This study was originally undertaken to determine the clinical value of estimating pepsinogen in the urine in cases of peptic ulcer because recent publications had shown that uropepsin (urinary pepsinogen) excretion in ulcers differed from normal controls. Briefly, the state of knowledge of pepsinogen when this study was undertaken was as follows: pepsinogen was discovered by Langley in 1881 and eventually isolated in 1958 by Herriot who described its physico-chemical properties. It was known to be formed in the stomach wall and mainly secreted into the stomach where it was irreversibly changed into pepsin in the presence or hydrochloric acid. None was reabsorbed and this pepsin was destroyed in the alkaline small intestine. Some pepsinogen diffused directly into the blood stream from the peptic cells and as far as could be ascertained was lost, till it appeared in the urine - a fact discovered by Brucke in 1861. Its transport to and the mechanism of its excretion by the kidney were the subject of hypothetical discussion only. In disease urinary pepsinogen had been studied for some time and the final conclusions were that it was increased in ulcers, especially duodenal ulcers and decreased or absent in pernicious anaemia. It was apparent early in this study that investigation of urinary pepsinogen alone would be of little value in advancing the knowledge of the normal and abnormal physiology of pepsinogen in the human. The investigation was then extended to study the pathological disturbances of urinary pepsinogen more closely, and if possible to determine what happened to pepsinogen between the stomach and the urine. This latter project became possible after the development of a technique not previously described for determining blood pepsinogen and it was found that pepsinogen diffuses from the peptic cells into the blood, and circulate as free pepsinogen in the plasma. From the plasma it is freely diffused through the body and filtered through the glomerular membrane and then reabsorbed in the tubules of the kidney to the extent of 65 - 95%. This new concept of pepsinogen excretion by the kidney calls for a re-orientation of the conclusions previously held of the significance of the urinary pepsinogen in disease, In this report, an attempt is made to present the whole cycle of pepsinogen metabolsim from its formation in the stomach to its appearance in the urine, with-normal and abnormal variations, as a unified concept. While in places comments or conclusions may appear dogmatic, it is realized that this study has produced more questions than answers. It is hoped, however, that a small contribution will have been effected by this work towards a better understanding of the direction of further advances in the knowledge of the aetiology and pathological behaviour of peptic ulcers.