With an attempt to clarifying the mechanism of hypoproteinemic complication in protein- losing gastroenteropathy, the phenomenon of plasma protein exsudation into the alimemtary tract was investigated by the dynamic analysis of albumin metabolism using 131I-labelled albumin (RISA) and the 131I-labelled polyvinyl pyrrolidone (131I-PVP) test on 29 patients with hypoproteinemia due to various causes (protein-losing gastroenteropathy, congestive heart failure, liver cirrhosis, anorexia nervosa, miscellaneous group) In 8 cases of protein-losing gastroenteropathy, the total exchangeable albumin (TEA) was 152.5±32.6gm or 3.78±0.62gm/kg on the average, markedly lower than the control (260.0±52.3gm or 5.17±0.85gm/kg). Especially, the circulating albumin pool (CAP) was 50.0±15.0gm or 1.31±0.32gm/kg on the average, showing a greater tendency to decrease in comparison with the control (103.8±20.3gm or 2.09±0.28gm/kg). The half-life of albumin in blood (T1/2) was markedly shortened to 4.3±1.6 days on the average in all the cases examined as compared with the control (13.4±3.0 days). The albumin turn over rate was significantly increased to 17.00±5.40%/day on the average as compared with the control, 5.38±1.17%/day. In the metabolically homeostatic condition, the amount dissolved is equal to the amount synthesized. The albumin synthesized in this disease amounted to 0.669gm/kg per day on the average, being greatly increased as compared with the control (0.274gm/kg per day). In short, no disturbance of albumin synthesis was demonstrated in this disease. Consequently, it was suggested that complication of hypoproteinemia in this disease might be caused by a failure in establishment of the metabolic equilibrium probably due to the theoritical amount remarkably surpassing the synthesizing ability of the liver or due to the disturbed dissolution and reabsorption of the exsudated protein. The 131I-PVP test was 1.44% to 13.96% (less than 0.74% in the control), demonstrating the exsudation of plasma protein into the alimentary tract in all the cases. In congestive heart failure, liver cirrhosis and miscellaneous groups, none of the cases was positive in the 131I-PVP test. These disease groups showed a decrease in TEA and CAP, prolongation of T1/2, and a decline in the albumin turnover rate. The amount of albumin dissolved (=synthesized) was observed to decrease. The complication of hypoproteinemia in these disease groups was proved to have arisen from a disturbance of albumin synthesis through a mechanism quite different from that of protein-losing gastroenteropathy. In respect to the mechanism for exsudation of plasma protein into the alimentary tract, it was supposed that the mechanism might be evidently different between the cases where the primary changes were present in the alimentary tract and the cases of congestive heart failure. In the comparative study of constrictive pericarditis and congestive heart failure, it was difficult to attribute this phenomenon only to the extent or duration of venous pressure elevation, but it seemed reasonable to consider that the mechanism might be additionally participated by a stagnant lymph stream or by regeneration of a collateral against obstruction.
In 1965, the Meeting of Japanese Gastroenterology Society had a proposal of the standard method for the determination of serum transaminase activty. This is based on the Reitman-Frankel method and its activity is represented by Karmen Unit. Several kinds of reagent kits, that is matched to this standard method have coming into the market. However, these kits have large deviation in measurement values. This first cause, we think, is that this standard method has no indication about the purity of the reagents. So we checked the purity of the reagents, and studied to decide their concentration to agree with the Karmen unit. Having obtained considerable data, we make a report as follows.
An attempt was made to clarify the pathogenesis of pancreatic lesions in cirrhosis of the liver. The pancreas was studied histologically in 45 autopsy cases with liver cirrhosis and 30 control cases without hepatic, pancreatic and cardiac diseases. Interstitial leukocytic reaction of mild to moderate degree was found in the pancreas of 42% of cases with cirrhosis. Mild to moderate parenchyma) necrosis of the pancreas was observed in 47% of cirrhotics. There was mild to severe fibrosis of the pancreas in 78% of cirrhotics. These incidences of pancreatic lesions of cirrhotic group were significantly higher than those of the control group. Inflammatory or necrotic changes were almost exclusively concurrent with fibrosis. On the other hand, fibrosis was not always accompanied by the other two pancreatic lesions. Therefore fibrosis was considered as the most fundamental lesion of the pancreas in cirrhosis of the liver. Iron deposit was revealed in eight of 27 cirrhotic cases. In cirrhotics with moderate to severe fibrosis of the pancreas, bromsulphalein excretion was significantly delayed comparing to those with mild or no fibrosis. Splenomegaly (over 200g) was found in 20 of 37 cases with cirrhosis. Esophageal varices were seen in 26 of 30 cases with cirrhosis. Incidences of pancreatic lesions in cases with splenomegaly, were not higher than those in cases without splenomegaly. So it was suggested that portal hypertension was not the sole contributory factor on the development of pancreatic lesions in liver cirrhosis, although it would not be neglected as a participating factor of the lesions. Eleven of 30 cases with cirrhosis consumed more than 180ml of Japanese Sake per day in averages when those were alive. In these cases, pancreatic lesions were not severe comparing to cases in which consumption of the alcoholic beverage was below 180ml per day. Therefore it appears that alcohol was not the major factor of the pancreaticc lesions. It would be concluded that pancreatic lesions occur in cirrhosis of the liver in significantly high incidences. Any single factor such as portal hypertension, alcohol ingestion or iron deposits might not be the sole cause of pancreatic lesions. Here arises the possibility that multiple factors participate in pathogenesis of the pancreatic lesions in cirrhosis of the liver.
In the previous paper, high incidences of pancreatic lesions, especially pancreatic fibrosis, in hepatic cirrhosis were reported. Here an attempt was made to study exocrine function of the pancreas in chronic liver diseases. Fecal excretion of orally administered 131I-labelled triolein was abnormally high in one of 14 cases with cirrhosis of the liver. In none of 12 cases with cirrhosis, fecal excretion of 131I-labelled serum albumin administered by mouth was abnormally increased. These findings suggest that in cirrhosis of the liver digestion and absorption of fat are impaired in some cases, but those of protein are not impaired. Pancreozymin-secretin test was performed in 12 patients with cirrhosis, 6 patients with chronic hepatitis and 11 controls. After secretin stimulation, volume of duodenal contents was abnormally increased in eight of 12 cases with cirrhosis and in three of 6 cases with chronic hepatitis. Icteric indices of duodenal contents of the groups with hepatic diseases were higher than that of the control, 20 to 60 minutes after secretin stimulation. These findings suggest that considerable part of increased duodenal contents was derived from bile and that increased secretion of bile or pancreatic juice might be ascribed to delay in inactivation of secretin in damaged liver. Thirty to seventy minutes after pancreozymin stimulation, increased duodenal fluid did not dilute amylase activity in chronic hepatitis and hepatic cirrhosis. Therefore it seems that inactivation of pancreozymin is also hindered in the group with chronic liver diseases. Maximal bicarbonate concentration of duodenal contents was lowered in two of 12 cirrhotics and in none of parients with chronic hepatitis. In 10-minute period after pancreozymin stimulation, amylase activity was moderately depressed in three of 12 cirrhotics, but it was not decreased in cases with chronic hepatitis. Total amylase output was not lowered in both cirrhosis and chronic hepatitis groups. Therefore it would be concluded that in cirrhosis of the liver, impairment of exocrine pancreatic function is found, but it is not such a degree as to cause hinderance of digestion of carbohydrates.
There had been many reports on the lipid digestion-absorption tests with 131I-triolein and 131I-oleic acid. However, the standard methods of the absorption tests had not been established and there remained many problems to resolved. Several problems were investigated by the authors. The standard methods of both tests were established and the normal ranges (and abnormal value) were settled. The standard methods of 131I-triolein test and 131I-oleic acid test were performed on the patients with malabsorption syndrome, such as secondary malabsorption and maldigestive malabsorption, as well as cholecystectomized, gastrectomized, hepatopathic and diabetic patients. The data were summarized and the following results were obtained. 1) The Lugol thyroid blockade is necessary. 2) The fecal excretion ratio is more reliable and useful than the blood radioactivity. 3) It is recommended that 1ml per killogram body weight of cold meal (peanut oil 20: water 20: tween-80 1.5) shoud be given for 131I-triolein test, and 0.5ml per Kg body weight of clod meal (oleic acid 20: water 20: tween-80 1.5) should be given for 131I-oleic acid test. 4) The normal value of the fecal excretion is less than 2.0%. The border-line value is 2.1-4.0%. The abnormal value is more than 4.1%. 5) The difference of the value between control groups and abnormal groups is statistically significant. 6) Impaired function of lipid digestion-absorption is obviously detected by the absorption tests, but they are not specific for the causative disease. 7) Cholecystectomized group revealed marked impairement of lipid digestion-absorption conpared as control group, but the no difference was seen between cholecystectomized group and the cholecystopathic group. 8) Among the gastrectomized, the impairement of the lipid absorption was marked in totally gastrectomized group, moderate in BII group, and slight in BI group. 9) Hepatopathic patient showed impaired lipid digestion-absorption by 131I-triolein test as well as diabetic patient. The impairement was severer when a patient had both disease. However, there was no definite tendency in the hepatopathic or diabetic patient in 131I-oleic acid test.