The Kinetics of Organic Anion Excretion by the Liver in Acute Intermittent Porphyria

Abstract

1. The kinetics of disappearance from the blood of three organic anions were studied in patients with acute intermittent porphyria. Indocyanine green (ICG) and ['4C]bilirubin were cleared normally in this disease, whereas bromsulphthalein (BSP) was cleared at less than the normal rate. The first exponential component of the BSP clearance curve was normal in acute intermittent porphyria, but the second exponential component declined less rapidly than in normals. The abnormality was greater in symptomatic than in asymptomatic patients, but both groups were significantly different from normals.2. The data are discussed in terms of a previously published model of BSP metabolism. The findings suggest normal BSP uptake initially by the liver with increased regurgitation of dye into the blood and decreased excretion of BSP from the liver cell into the bile.3. In contrast to human acute intermittent porphyria, plasma clearance of BSP was greatly increased in experimental porphyria. This was associated with an increased level of BSP conjugating enzyme in the liver in experimental porphyria.4. The BSP retention in acute intermittent porphyria, along with certain other findings, raises the question of the existence of an 'oestrogen effect' in this disease, but further studies will be required to determine whether the mechanism of BSP retention is identical to that produced by oestrogen.Acute intermittent porphyria (AIP) is a type of hepatic porphyria in which overproduction of porphyrin precursors occurs in the liver (Tschudy et al., 1965;Nakao et al., 1966;Dowdle, Mustard & Eales, 1967). Standard tests of hepatic function in this disorder have generally been normal with the exception of the bromsulphthalein (BSP) test (

Hepatocellular Carcinoma in Patients with Acute Intermittent Porphyria

“…This appears to be the only significant abnormality of testable hepatic function reported so far and is not accompanied by intrinsic structural disease (15,16). The bromsulphthalein retention in porphyric patients, which tends to parallel the activity of the disease, suggests an "estrogen effect" in this disease (18).…”

Iron and the liver Acute and long-term effects of iron-loading on hepatic haem metabolism

“…Potentiation of induction of S-aminolaevulinate synthetase by iron-dextran and 2-allvl-2-isopropylacetamide Iron, administered as ferric citrate by stomach tube, has previously been shown to potentiate the induction of 5-aminolaevulinate synthetase caused by porphyrogenic chemicals such as 2-allyl-2-isopropylacetamide (Stein et al, 1970;Bonkowsky et al, 1979b). As Fig.…”

“…Enteral ferric citrate potenti-Abbreviation used: GSH, reduced glutathione. ates induction by 2-allyl-2-isopropylacetamide of 5-aminolaevulinate synthetase, the rate-controlling enzyme of hepatic haem synthesis (Stein et al, 1970). More recently, we showed that ferric citrate increases the turnover of hepatic haem (Bonkowsky et al, 1980a).…”

Antipyrine metabolism in acute hepatic porphyria in relapse and remission.

“…Altered hepatic metabolism has also been reported for salicylamide (Song et al, 1974) and aminopyrine (Ostrowski et al, 1983) but not for phenylbutazone (Anderson et al, 1976) or indocyanine green (Stein et al, 1970). The reduction in antipyrine volume of distribution in all the porphyric patients was unexpected and remains unexplained.…”