Grindlay, John H.

The theoretic considerations which indicate that fibrocystic disease of the pancreas is the result of a congenital deficiency of secretin have been outlined. The varied clinical and pathologic manifestations of this disease can, in our opinion, be more nearly adequately explained by this hypothesis than by any of the other current theories. The absence of secretin (S1) in the upper part of the intestinal tract of a patient with fibrocystic disease of the pancreas lends support to this theory; which is to say, that the condition is the result of a congenital deficiency of secretin. It has been shown to be possible to extract secretin from the upper part of the intestinal tract of persons two months to 73 years old. The only consistent, failures occurred in work with patients in the neonatal period. Successful extraction of secretin from these patients in the neonatal period can be carried out, however, by combining the crude extracts obtained from a number of patients. The extraction of secretin is successful if it is done up to 15 hours postmortem. If the specimen is kept in a frozen state, extraction can be delayed without loss of activity as long as 39 days. Because this method of extraction is successful in individual cases at necropsy, it becomes possible to correlate the presence or absence of secretin with varying pathologic conditions. This, in turn, may open up a broad field for the investigation of many pancreatic and intestinal disturbances in addition to fibrocystic disease of the pancreas.

Dogs with biliary fistulas metabolized triiodothyronine rapidly to inorganic iodide, as did normal dogs. The amount and distribution of I131 compounds in the urine were not greatly altered by withdrawal of the bile, which contained about one-fourth of the I131 administered. Dogs with biliary obstruction excreted more of compounds b, iodide and the conjugate than normal dogs. The absence of enterohepatic circulation of metabolic products of triiodothyronine usually excreted in the bile did not appreciably alter the products or rate of metabolism of triiodothyronine. Some of the same products of triiodothyronine appeared in both bile and urine but there was very little inorganic iodide in the bile and much more of the glucuronide and the water-soluble, column residual fraction.

The total amount of I131-containing compounds excreted in the urine of the dehepatized dog receiving either radioactive thyroxine or triiodothyronine is similar to that of the normal dog receiving similar injections. The important role of the liver in the deiodination of thyroxine and triiodothyronine is indicated by the failure of the liverless animal to convert these compounds to inorganic iodide as completely as does the normal dog. Only a small percentage of the I131 compounds excreted by the liverless dog appears as inorganic iodide. The most abundant iodine compound in the urine of the dehepatized dog is a conjugate of thyroxine when thyroxine is injected, and an unidentified compound, b, when triiodothyronine is injected.

Dogs excreted the same compounds in the urine after injections of radioactive thyroxine whether they were normal or had a biliary fistula or biliary obstruction. Dogs with biliary fistulas excreted more of the conjugate in the urine than did normal dogs. Dogs with biliary obstruction excreted the largest amounts of the conjugate and also showed increased levels of the conjugate in the blood. All the changes were minor, however, compared to those found after hepatectomy. No evidence was found for conversion of thyroxine to triiodothyronine or tetraiodothyroacetic acid, but the present studies would not exclude the possibility that these substances are rapidly transformed intermediates in the metabolism of thyroxine.

Observation of the hilar lymphatics from 100 canine livers seen at operation disclosed two drainage pathways: 1) a main hilar system, draining predominantly the right lobes and 2) an accessory hilar system, draining mainly the left lobe. In 94% of the animals all of the hilar lymph seemed to pass into one common efferent trunk which then discharged it into the cisterna chyli. Apparently, 69% of the animals had a lymph vessel large enough to permit cannulation for physiologic studies. From a study of five dogs in which the gallbladder was removed and the common bile duct ligated and in which there were fistulas of both the hilar lymph trunk and the thoracic duct, it was concluded that, normally, about 80% of the lymph leaving the canine liver probably travels by the hilar route and the remaining 20% by the hepatic venous lymph route. The mean flow of hilar lymph from the liver during biliary obstruction in 20 unanesthetized animals was 0.66 ml/kg body weight/hr., the standard error of the mean being ±0.07.

Total fatty-acid output in the intestinal lymph in rats and in the thoracic-duct lymph in dogs was studied during fasting and during a fat-free diet period. Daily total fatty-acid output in the intestinal lymph was found to be fairly constant during fasting or when the rat was fed a fat-free diet. There is an inverse relationship between total fatty-acid concentration and the volume of intestinal lymph. In the absence of pancreatic juice or of both bile and pancreatic juice, the total fatty-acid output in the thoracic-duct lymph in dogs was decreased to one-third or one-fourth that of the normal dog. The endogenous lipid metabolism of the intestine is discussed in relation to steatorrhea.