A dynamic study on albumin metabolism in various liver diseases was undertaken with the purpose of elucidating the mechanismus operating in the process to chronic hepatitis from acute hepatitis and also in progressive liver cirrhosis. The turnover study of albumin metabolism was calculated by the method of Berson, Campbell, Mathews using 131I labeled human serum albumin produced by DINABOTT laboratorus. The subjects studied were 88 cases of various liver diseases and 17 hospital controls. A correlation efficiency of 0.927 was observed between albumin turnover value (ATOV) and serum albumin concentration (SA). Regression line of ATOV=70SA-54. Various values of albumin were changed with age of the subjects; a decreased tendency was observed in ATOV, SA, total exchangeable albumin (TEA), extravascular albumin (EVA) whereas an in creased tendency was observed in half life of disappearance curve(T1/2), plasma volume. The values of ATOV, TEA and EVA were decreased in the florid stage as well as relapsing stage of subacute hepatitis. In the cases progressing to liver cirrhosis from subacute hepatitis showed more remarkable decrease in the value than the cases with compensated established cirrhosis. This phenomenon was interpreted as the reduction of albumin synthesis due to severe liver cell injury. In the cases with chronic hepatitis, on the other hand, the various values of albumin metabolism showed slight reduction, however no significant difference was observed between active and inactive chronic hepatitis. The cases with active chronic hepatitis progressing to liver cirrhosis showed lesser value in ATOV. The therapeutic use of 6 mercaptopurine (6MP) at the daily dosis of 50 to 75mg induced as slight reduction in ATOV and TEA. Thus a tendency shifting to the state of decreased synthesis of albumin following the medication of 6MP in the cases with posthepatitic liver cirrhosis in comparison with chronic hepatitis. The reduction of ATOV was smaller by Imuran as compared with 6MP. In contrast, value of ATOV was increased by glucocorticoid.
The hypoalbuminemia found in patients with cirrhosis of the liver has been partially explained by a decrease synthesis of albumin as indicated by the decrease in albumin turnover value (ATOV). A gastrointestinal losing of proteins was looked for in this study as a possible factor contributing to the hypoalbuminemia in cirrhosis of the liver. A method for the simultaneous measurement of gastrointestinal loss of proteins and total albumin turnover entailing the use of combination of 131I-albumin and 51Cralbumin was used. Albumin turnover was estimated by measurement of 131I-albumin disappearance and urinary excretion. Gastrointestinal protein losing was estimated from the rate of fecal excretion (FE) of 51Cr and plasma albumin- 51Cr disappearance, and both data were related to the values calculated from the 131I-albumin disappearance. The FE rate in normal control of 5 cases was 0.35±0.1% of the administered activity of 51Cr-albumin. The rate in 26 cases of liver cirrhosis was 0.54±0.2% and was not significantly different from that of normal control. The correlation coefficient between serum albumin concentration (SA) and FE was -0.351. A high FE rate of 1% was found in one case of cirrhosis of the liver, which had tarry stool and positive occult blood reaction (+++). A relative fecal excretion (RFE) as expressed by FE/TEA ×1000(%/mg) was 2.28±1.43 in cases of cirrhosis of the liver and 1.24±0.36 in normal control; the former was significantly high (P>0.05) in comparison with the latter. Five cases of decompensated severe liver cirrhosis with ascites, varices and jaundice showed an especially high RFE of 4.73±1.02 (P> 0.01). One case with tarry stool gave a RFE of 13.5. However, the RFE of milder cases of cirrhosis and chronic hepatitis revealed no significant difference from that of normal control. It was concluded that the gastrointestinal losing of proteins in addition to the decrease in synthesis of albumin elicited the decreased SA and TEA in decompensated cirrhosis of the liver.
Fine Structure of hepatic parenchymal cells in jaundice has been dealt with in many studies. Nonetheless, there still remains uncertainty regarding the mechanism of bilirubin metabolism and jaundice. For the purpose to clarify this problem, hepatic parenchymal cells were observed by electron microscope. Eight liver biopsy specimens were used for this study. One was from normal dog, and four were from dogs with obstructive jaundice due to ligation of bile duct. Three were from dogs with hyperbilirubinemia induced by intravenous unconjugated bilirubin infusion. In addition to this, human liver biopsy specimens were used. One was from patient with obstructive jaundice due to the carcinoma of the head of pancreas. The others were from the patient with cholestatic jaundice of pregnancy and from the patient with Dubin-Johnson syndrome. Results of the observation were as follows. (1) Increase in number of the smooth surfaced endoplasmic reticulum and lysosome. (2) Increase in width and density of the pericanalicular ectoplasm. (3) Changes in morphology and number of bile canaliculus. (4) Changes of intercellular space and surface to neighbouring hepatic parenchymal cells. At first, lysosomes appeard near the Golgi complex and as they increased in size and density, they were found remotedly from the Golgi complex. Bile canaliculi usually dilated and showed loss of microvill, or stunted microvilli. Moderately or highly electron opaque substance was seen in the lumen. After intravenous injection of bilirubin in dog, number of bile canaliculus increased. Surface to neibouring cells sometimes protruded microvilli or microvilli-like projections into intercellular space and in this space moderately or highly electron opaque substance was seen. From these results, we concluded as following. Uptake of bilirubin occurs without any morphological changes of sinusoidal surface. Smooth surfaced endoplasmic reticulum plays important role in conjugating and transporting bilirubin. Golgi complex and lysosome transport conjugated bilirubin. Most of bilirubn is excreted into bile canaliculi through pericanalicular ectoplam largely by diffusion without any defect of cell membrane and small amount of bilirubin into intercellular space and space of Disse. To increase capacity for excreting bile, at first, the bile canaliculi wind and dilate, then increase their number by ramifying. Excretion into intercellular space by diffusion and reversed pinocytosis plays an important role for occurence of jaundice.
A method for quantitative analysis of monosacharide and their polyols in serum, urine and liver by gas chromatography is described. These studies have been carried out with a Yanagimpto GCG-5DH with flame ionization detector using SE-30 column as liquid phase at 170°C. Analytical procedures were as follows: serum was deproteinized by the method of Somogyi and the supernatant was dried completely using rotary evaporator at 60°C. The residue was dissolved in anhydrus pyridine, and then trimethylsilylation was done adding hexamethyldisilazane and trimethylchlorosilane prior to injection to gas chromatograph. Urine, if not albuminuria, was dried without any treatment and trimethylsilylation was performed. Liver was homogenized in physiological saline with sodium fluoride and also deproteinized by the method of Somogyi. Following procedures were as same as serum. Sorbitol was used as internal standard according to the stability of its trimethylsilyl ether and appearing its peak between α-and β-glucose. Peak areas of glucose and xylitol obtained by gas chromatography showed to be proportional to their weights, but it was necessary to multiply the value obtained by gas chromatography by the coefficiency (0.92) for getting the weight of xylitol. Blood glucose levels determined by gas chromatography and auto analyzer method showed a satisfactory agreement. The average value determined by gas chromatography was 6.9% lower than that obtained by auto analyzer method. The anlytical examples of xylitol tolerance test to patients with liver disease and with diabetes mellitus were presented as the clinical application. This method is not also sensitive, but also accurate because non-sugar substances which give reducing reaction can not be determined. Therefore, this is a definitely exellent method for separation and determination of monosacharides and their polyols in blood, urine and various tissues, and is also available for detecting disorders of carbohydrate metabolism in clinical and experimental studies.
Rat experiments were undertaken to examine the alterations of steps involved in the transfer of BSP from blood to bile after the intravenous administration of sodium hippurate. 1) Following a single intravenous administration of BSP, biliary excretion of BSP was increased by hippurate. 2) Distribution of BSP after a constant infusion of BSP was estimated. Through the intravenous administration of hippurate, a distinct elevation of the maximal transport of BSP into bile (BSP-Tm), a significant increase of unconjugated BSP storage in the liver (BSP-S) and a moderate degree of choleresis were observed. 3) Through an addition of hippurate a significant acceleration of BSP-glutathione conjugating enzyme activity was observed on liver homogenate but no acceleration was noted on liver slices. 4) Through an addition of hippurate a slight degree of inhibition of BSP-binding affinity of serum albumin was observed. 5) It was concluded that an increased biliary excretion of BSP by sodium hippurate was resulted from a significant elevation of BSP-Tm and a slight degree of inhibition of BSP-binding affinity of serum albumin.
Rat experiments were undertaken to examine the alterations of steps involved in the transfer of BSP from blood to bile after the intravenous administration of sodium dehydrocholate (DHC). 1) Following a single intravenous administration of BSP, biliary excretion of BSP was increased by DHC. 2) Distribution of BSP after a constant infusion of BSP wasestimated. Through the intravenous administration of DHC, a distinct increase of bile output, a moderate degree of elevation of the maximal transport of BSP into bile (BSP-Tm) and a distinct decrease of hepatic storage of BSP (BSP-S) were observed. 3) Through an addition of DHC an inhibition of BSP-binding affinity of plasma albumin and a distinct acceleration of BSP-glutathione conjugating enzyme activity were observed in vitro. 4) It was concluded that an increased biliary excretion of BSP by DHC was resulted from an elevated BSP-Tm, increased bile output, inhibited BSP-binding of plasma albumin, increased BSP-glutathione conjugating enzyme activity and decreased hepatic BSP storage.
The effects of sodium dehydrocholate (DHC) upon the maximal transport of BSP into bile (biliary BSP-Tm), relative hepatic storage of BSP (BSP-S) and urinary excretion of BSP were estimated in normal persons and patients with liver disease. The biliary BSP-Tm and BSP-S were estimated according to the technique which was described by Adams and his co-workers (1966). The 24 hours' urinary excretion rate of BSP to the total infused BSP during the experimental period of the estimation of BSP-Tm was determined. Sodium dehydrocholate was infused intravenously at a constant rate of 10 to 15mg per minute during the experimental period of the estimation of BSP-Tm. The experiment with DHC was carried out 7 days before or after the control experiment. The following results were obtained. 1) The BSP-Tm and BSP-S were generally decreased and the urinary excretion of BSP was increased in the patients with liver disease. 2) The administration of DHC resulted in a slight increase of the BSP-Tm, a distinct decrease of the BSP-S, an increase of urine output and an increase of the urinary excretion of BSP especially among the patients with liver disease.