THE METABOLIC GRADIENT UNDERLYING PERISTALSIS
Journal of the American Medical Association
Why sometimes does it turn around and come back through the mouth? These questions are fundamental; and the future of gastro-enterology as an exact science depends on the fulness with which they are answered. Until we obtain such physiologic knowledge we must face the fact that in practice we are trying to repair a machine, the normal structure and workings of which are largely unknown to us. Naturally the results are often unsatisfactory, just as they would be if we were trying to repair
... ing to repair brokendown adding machines or wireless telephones. What could the heart specialist learn about the arrhythmias until Gaskell, McWilliam, His, Keith, Lewis and others showed him where the beat normally arises and how it is transmitted from sinus to ventricle? Given that information, the student of heart pathology became inspired and rejuvenated; his knowledge advanced by leaps and bounds ; and his textbooks had to be rewritten and remodeled. We should take hope from this good fortune which has come to our confrères and should seize on the methods of study which have been so productive in their bands. With these I believe we can advance to similar triumphs over the baffling problems in our own chosen field. We should study the gastro-intes¬ tinal tract in embryos and in lower and simpler forms of life; we should look for structural and metabolic differences in the neuromuscular apparatus in different parts of the tract, and we should study minutely the reactions of the muscular coat-its rhythmicity, irritability, conductivity, reaction to drugs, etc.-in different regions. As clinicians, we must get over the habit of thinking in terms of plumbing and rigid tubes held in one position. We must think instead of a muscular tube which has to contract in a coordinated way if material within it is to be pushed for many feet in one direction or the other. Six years ago I showed that there is a very definite gradient of rhythmicity in the muscle of the small intestine from duodenum to ileum1. It seemed to me then that this gradient of rhythmicity or perhaps some underlying gradient of tone might be the essential factor in determining the direction of peristalsis. This gradient might conceivedly be reversed by any distention, irritation or inflammation which would increase the tone and activity of the lower parts of the tract to a level above that maintained by the upper parts. In two papers2 I reviewed much of the litera¬ ture and showed how easily a great many clinical and roentgenologic observations can be explained on the basis of such a theory. I cannot see now why there should be any great difficulty in accepting this idea of a gradient of forces as a working hypothesis in the study of peristalsis. Wherever we find movement in this world we find a gradation of forces. Thus, water flowing in a ditch follows a gradient of gravity, i. e., the pressure on any one drop is greater on the upstream than on the downstream side. Electricity in a wire follows a gradient of potential or voltage ; in a battery it follows a gradient of chemical activity, flowing from regions in which oxidation predominates to regions in which reduction predominates. The impulse in the heart follows a gradient of rhythmicity; and accord¬ ing to Tashiro3 the impulses in nerves follow gradients of oxidation. In the stomach and intestine the con¬ tents move from regions of high rhythmicity, his;h irritability and high tone to regions of low rhyth¬ micity, low irritability and low tone. During the last two years I have been able to show that there is a definite gradient of oxidation and car¬ bon dioxid production in the intestinal wall, underlying and probably giving rise to the other gradients of rhythmicity, tone, etc.4. In other words, the chemical processes of life go on at a faster rate in the duodenum than in the ileum or colon. Theoretically, if we should speed up these processes in the' duodenum we might steepen the gradient and cause the food to go faster through the bowel ; if we should speed them up in the ileum so that they would be faster than those in the duodenum, we might reverse the gradient and stop the downward progress of food. Recent study has shown that the local life processes are greatly speeded up by inflammation5, so it may be that the hypermotility actually seen in many cases of duodenal ulcer and cholecystitis and the hypomotility with appendicitis are due to changes in the metabolic gradient brought about by these lesions. Galvanometric studies of bruised tissues suggest strongly that their metabolic rates are increased by the trauma6. If this be true in the intestine we can easily explain the fact that its contents cannot approach or pass through segments which have recently been pinched in hernial rings or maltreated at operations7. A local increase in the metabolic rate would make the gradient uphill in the section of bowel just orad to the lesion. There is yet another and perhaps an even more important way in which the gradient may be reversed. Child8 has shown repeatedly that tissues with a fast rate of oxidation are more susceptible to the effects of low concentrations of certain poisons, such as potas¬ sium cyanid, than are tissues with slow rates. If two lots of small planarian worms of different ages are put into a weak solution of potassium cyanid, the younger ones, with the faster metabolic rate, die first. Similarly, if children and old men were to be put into a room full of ether vapor, the children would prob¬ ably all go to sleep first. Child showed that in some of the lower forms of life which have rows of swim¬ ming plates along their sides, the direction of the beat can be reversed by potassium cyanid because the paeemaking region suffers most from the effects of the drug. Using excised segments from different parts 3.