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T G Richards

Publications and source records attributed to T G Richards.

16 recordsLinked to original sources
PubMed1977

Possible explanations for the differences in secretory characteristics between conjugated and free bile acids.

1. The hepatic extraction fraction and maximum excretory rate of conjugated cholate are greater than those of free cholate (studied after acute taurine depletion); the possibility that this difference might be due to greater bile-to-blood back-diffusion of un-ionized cholic acid (pKa 5-5) compared to that of taurocholic acid (pKa 2) has been investigated by varying the pH of bile by secretin or acetazolamide administration in the anaesthetized dog. 2. The mean biliary pH during free cholate excretion in the control state in twenty-three experiments was 7-5 (at which approximately 1% of cholate is un-ionized). Three to fourfold changes in the hydrogen ion activity of bile (which resulted in changes of the same magnitude in the percentage of un-ionized cholic acid) had no significant effect on the total (mainly free) cholate maximum excretory rate. It is concluded that back-diffusion of un-ionized cholic acid in the bile ducts is not an important determinant of the secretory performance of free cholate. 3. The bile flow rate associated with mainly free cholate excretion is much higher than that associated with taurocholate excretion at the same rate; the extra bile flow appears to arise largely by means that are independent of the osmotic effect of cholate excretion, as the osmotic coefficient (osmolality/total solute concentration) of bile containing mainly free free cholate (calculated directly) was only slightly greater than that of bile containing mainly taurocholate (obtained by extrapolation) at the same total cholate concentration. 4. The peak hepatic excretory rate of taurocholate following the instillation of the entire contents of the gall-bladder of a fasted dog into the distal ileum was only about one fifth of the maximum rate attainable; at the peak rate taurocholate is almost completely removed in the first passage of blood through the liver.

Animals↗
PubMed1976

Measurement of liver blood flow by means of a single injection of bromosulphthalein, without hepatic venous catheterization.

1. A method is described for the measurement of liver blood flow without hepatic venous catheterization by the injection of the a single dose of bromosulphthalein and the analysis of the graph of the plasma disappearance of the indicator. 2. The rationale of the method was tested in three systems which covered a wide range of flow rates. The first system was a physical model with a haemodialyser in which the calculated flow could be compared with the flow measured directly. The second was in anesthetized dogs, in which the calculated flow was compared with that measured by continuous infusion and hepatic venous catheterization, based on the Fick principle. The third system was in unanaesthetized turkeys, in which metabolism of bromosulphthalein does not occur. The calculated flow was compared with the flow measured simultaneously by the uptake of collodial particles by the Kupffer cells. 3. In all three systems the correspondence between the two methods of measuring liver blood flow was good, the differences between them being not statistically significant. 4. The method has been applied to measurements of liver blood flow in man and animals and gives results comparable with those reported by other workers.

Animals↗
PubMed1976

The secretory characteristics of dehydrocholate in the dog: comparison with the natural bile salts.

1. During dehydrocholate administration in the taurine replete dog, the maximum excretory rate of total bile salt (almost entirely dehydrocholate derivative, mostly conjugated) was 3-84 +/- 0-53 (S.D.) mumole/min. kg body wt. (eleven experiments). This was much less than the excretory maximum previously obtained for taurocholate (8-64 +/- 1-31 (S.D.) mumole/min. kg total cholate, mostly conjugated). 2. The superimposition of taurocholate infusion did not cause any significant change in the 'dehydrocholate' maximum but taurocholate itself was excreted into bile at no more than about half its normal maximum. When taurocholate maximum excretion was established first, it was reduced by dehydrocholate administration. In both types of experiment the joint bile salt excretory maximum was of the same order as that of taurocholate alone, provided taurocholate made up at least 40-50% of the total bile salt. 3. When taurocholate administration was stopped, the maximum excretory rate of 'dehydrocholate' rose to values up to 63% above the initially determined excretory maximum; the enhanced 'dehydrocholate' excretory maximum, when calculated for optimal conditions, approached that of actively conjugated vholate, even though the effective 'dehydrocholate' concentration in bile was ten to twenty times the critical micellar concentration of taurocholate. This suggests that the effective bile salt concentration in bile is not an important determinant of the secretory performance of a bile salt. 4. To explain findings (2) and (3) it is necessary to postulate that taurocholate has both a facilitatory and an inhibitory action on 'dehydrocholate' excretion. The facilitatory action, which persists after taurocholate has left the animal, may consist either of an increase in the maximum rate at which modification of dehydrocholate takes place within the liver cell, or an increase in the number of functioning 'carriers' for 'dehydrocholate' transfer. The data suggest that the inhibitory effect is due to the competitive interaction that also appears to exist between the two bile salts. 5. The increase in bile flow rate per unit increase in 'dehydrocholate' excretion (15 ml./m-mole) was about twice that obtained for taurocholate. There was no significant formation of micellar aggregates during 'dehydrocholate' excretion, as judged from the total electrolyte concentration of bile and its osmalality. 6. During the excretion of 'dehydrocholate'-taurocholate mixtures (approximately 1:1) at submaximal rates the associated bile flow rate was not less than the sum of the separate components, thus suggesting that 'dehydrocholate' was not being incorporated in taurocholate mixed micelles.

Animals↗
PubMed1967

The influence of conjugation of cholic acid on its uptake and secretion: hepatic extraction of taurocholate and cholate in the dog.

1. Sodium taurocholate or cholate was administered systemically at a constant rate of about 2.9 mumole/min.kg body wt. to anaesthetized dogs in which the common bile duct had been cannulated. In steady-state conditions blood was sampled from systemic and hepatic veins and the fraction of bile salt removed in a single passage through the liver was determined. Total hepatic blood flow was estimated by application of the Fick principle.2. The hepatic extraction fraction for synthetic taurocholate in ten experiments was 92%+/-5% (S.D.) over the blood flow range encountered (1.1-2.8 ml./min.g liver). The extraction of cholate extensively conjugated in the liver before excretion into bile was 79%+/-8% (S.D.) (twenty-one observations, thirteen experiments). In circumstances of similar hepatic blood flow the extraction of cholate transferred to bile in the free form (after acute taurine depletion) was significantly less than that of either synthetic taurocholate or cholate which could be actively conjugated before excretion. These results, which are discussed and criticized, support previous work on the advantage of conjugation in the transfer of cholic acid from blood to bile.3. The hepatic clearance of bile salt decreases with increasing administration rate, but the values obtained may be influenced by changes in hepatic blood flow. With regard to taurocholate an increase in total hepatic flow was observed when its administration rate exceeded about 5 mumole/min.kg body wt.4. The secretory maximum for glycocholate, a bile salt not normally found in dog bile, was of the same order as that for taurocholate.

Animals↗
PubMed1966

Factors determining the maximal rate of organic anion secretion by the liver and further evidence on the hepatic site of action of the hormone secretin.

1. Bromsulphthalein (BSP) was administered throughout the experiments at a constant rate well in excess of its excretory rate, to anaesthetized dogs in which the common bile duct had been cannulated. The maximal excretory rate of BSP into bile (BSP T(m)) obtained in this manner was greatly elevated by choleresis arising from the administration of bile salt (usually taurocholate) at constant rate.2. When bile flow rate was increased in stages by raising the taurocholate administration rate, successive increments in BSP excretion rate were obtained up to a limiting value of about 3 times the original T(m). Beyond this point further increases in taurocholate administration rate caused either no further enhancement of BSP T(m) or a decline in the extent of enhancement produced at a previous lower rate of infusion.3. When taurocholate maximal secretion was established first, the subsequent administration of BSP at progressively increasing rates led to reduction in the taurocholate secretion rate.4. Portal infusion of secretin at constant rate (usually 0.2 units/kg body wt. min) which caused substantial increases in bile flow rate, had no effect on BSP T(m). Increases of bile flow rate of the same order following constant taurocholate infusion produced marked elevation of the BSP T(m).5. These findings are discussed and the following conclusions reached:(a) The limiting factor in BSP maximal transfer is the concentration of BSP in bile; increased bile flow rate at the site of BSP excretion (canaliculi) produced by bile salt administration permits an increase in the original T(m) to occur without the limiting biliary concentration being exceeded.(b) There is excretory competition between BSP and bile salt but over a certain range of bile salt administration the facilitatory effects of increased bile flow rate outweigh the inhibitory effects due to competition.(c) Since secretin administration had no effect on BSP T(m), it is likely that the hydrocholeresis it produces originates downstream from the canaliculi, i.e. in the bile ductules or ducts; this supports previous evidence obtained in a different manner.

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