A comparative evaluation of the newer liver function tests

Mateer, John G.; Baltz, James I.; Marion, Donald F.; Hollands, Robert A.; Yagle, Elizabeth M.

doi:10.1007/bf02996988

Am. J. Dig. Dis.

1942

DOI: 10.1007/bf02996988

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A comparative evaluation of the newer liver function tests

John G. Mateer

James I. Baltz

Donald F. Marion

et al.

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1942

1959

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Cited by 43 publications

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“…Removal is impaired in the presence of hepatocellular damage, and BSP retention in blood has proved to be a sensitive index of hepatic dysfunction (3,4). Although BSP has been used in the clinical evaluation of hepatic disease for over 30 years, the precise mechanisms by which it is handled by the liver remain poorly understood.…”

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confidence: 99%

The Biliary Excretion of Sulfobromophthalein Sodium (Bsp) in the Rat as a Conjugate of Glycine and Glutamic Acid *†

Combes¹

1959

J. Clin. Invest.

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Sulfobromophthalein sodium (BSP) is a phthalein dye that is removed from blood predominantly by the liver and excreted into the bile (2). Removal is impaired in the presence of hepatocellular damage, and BSP retention in blood has proved to be a sensitive index of hepatic dysfunction (3,4). Although BSP has been used in the clinical evaluation of hepatic disease for over 30 years, the precise mechanisms by which it is handled by the liver remain poorly understood.Based on a considerable body of evidence (5-14), it is currently believed that hepatic removal of BSP depends upon the simultaneous operation of at least two processes: 1) uptake of BSP by liver cells in an amount proportional to a given blood level, and 2) transfer from blood to bile by a rate-limited transfer mechanism. Recently, a chromatographic and chemical analysis of BSP as it appeared in bile was undertaken in our laboratory in order to examine the biochemical mechanisms involved in its excretion. In a preliminary communication (1), it was reported that BSP is excreted as four distinct compounds in the bile of the rat. The major excretory product was demonstrated to be a conjugate of BSP with the amino acids, glycine and glutamic acid. A more complete presentation of these and additional observations forms the basis of the present report. MATERIALS AND METHODSThe standard BSP used in these studies was the 5 per cent solution sold commercially by Hynan, Westcott and Dunning, Inc., of Baltimore, Md. Chromatographically * A preliminary report of these studies has been previously published (1). The common bile ducts of rats (Long Evans, Wistar) were cannulated with fine polyethylene tubing under ether anesthesia. Bile was allowed to drain into small bottles while the rats were gently restrained in special cages. After collection of a control sample of bile, varying doses of BSP were injected and additional bile samples were obtained. The bile samples were treated as follows:1) Quantitation of BSP in bile. Colorimetric determinations were made on a Beckman DU spectrophotometer, set at 575 mu, on appropriately diluted bile specimens to which alkali had been added. Complete recovery of BSP was obtained over the range of concentrations, 30 to 350 mg. per cent, encountered in bile in these studies.2) Chromatography of BSP compounds. Bile samples were applied 25 Iul. at a time as a band 5 inches wide on Whatman No. 1 filter paper strips (6 X 21 inches). Each 25 ,IA. volume was dried with cold air from a hair dryer before the next aliquot was added to the paper. A total of 100 to 200 ul. of bile containing 0.045 to 0.35 mg. of BSP was applied at the origin. The chromatograms were then developed for 16 to 20 hours at 22°C. in a descending system consisting of glacial acetic acid: water: n-propyl alcohol (1: 5: 10 v/v). After the papers were dried, BSP bands were identified by: 1) the development of a purplish color when exposed to ammonia vapors, and 2) their absorption in the ultraviolet range (X max = 232 mM) .3) Quantitation of BSP on chromatograms. In s...

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confidence: 99%

The Biliary Excretion of Sulfobromophthalein Sodium (Bsp) in the Rat as a Conjugate of Glycine and Glutamic Acid *†

Combes¹

1959

J. Clin. Invest.

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“…(Hanger, 1939;Pohle andStewart, 1941 Rosenberg, 1941 ;Nadler and Butler, 1942;Mateer et al, 1942;Yardumian and Weisband, 1943) to be an extremely sensitive test in the early detection of hepatic insufficiency. The test was found to be of considerable value in prognosis in cases of acute infective hepatitis ; the persistence of a strongly positive reaction indicates severe liver damage.…”

mentioning

confidence: 99%

“…It is recognized that many of the liver function tests in common use fail to detect early or mild liver damage ; positive results are often found only in the advanced stages of the disease when clinical symptoms are already manifest. The cephalincholesterol flocculation test has been shown by several American workers (Hanger, 1939;Pohle andStewart, 1941 Rosenberg, 1941 ;Nadler and Butler, 1942;Mateer et al, 1942;Yardumian and Weisband, 1943) to be an extremely sensitive test in the early detection of hepatic insufficiency. The test was found to be of considerable value in prognosis in cases of acute infective hepatitis ; the persistence of a strongly positive reaction indicates severe liver damage.…”

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Flocculation Reaction as Test of Liver Function

Dick¹

1945

BMJ

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MERITISHhas persisted. When a large amount of fluid was drunk it was excreted too slowly and the specific gravity of the urine failed to fall as low as it should have done, indicating abnormal glomerular filtratio&n. Neither did water deprivation raise the specific gravity to the levels which ought to have been reached -an indication of impaired tubular absorption.The transient albuminuria in this case was almost certainly due to sulphanilamide poisoning: it coincided with the discovery of crystals and red cells in the urine and heralded the appearance of agranulocytosis. (Incidentally this emphasizes once again the danger of uncontrolled application of sulphanilamide powder to ulcers; the response of the severe leucopenia to massive doses of pentnucleotide is also worthy of notice.) If the albuminuria had been due to the effects of the original injury, as was presumably the case in the second patient, it should have been evident when the blood urea 4was at its maximum. During the post-traumatic period neither patient passed red cells in excess, no casts were found, and spectroscopic examination for haemoglobin and muscle pigments was negative.The kidneys of the'second patient were examined post mortem and were similar to those already described (Darmady et al., 1944), the pathological lesions being comparable to those of the crush syndrome and largely confined to the tubules. In addition a few sulphanilamide crystals were present. The changes were certainly insufficient to explain urea retention on the pLurely mechanical basis of tubular obstruction, and the glomeruli were comparatively healthy. The blood urea does not rise in nephrosis in which pathological changes are confined to the tubules. It therefore seems more likely that the cause of renal failure and of the damage to the tubules is anoxia resulting from vasoconstriction of the renal arteries during the stage of shock, aggravated by blood loss, a fall in blood pressure, and dehydration. This supposition is favoured by the demonstration of similar alterations in the tubules after temporary clamping of the renal vessels (McEnery et al., 1927) and by the theory propounded by Maegraith and Findlay (1944) that peripheral vascular atony with redistribution of renal blood flow explains the suppression of urine in blackwater fever. The action of myotoxin may be accounted for in a similar manner. Oedema of the kidneys and rupture of some of the renal capillaries occur during the anoxic period, and may be responsible for the slow recovery of renal function after the systemic blood pressure has risen to normal. It has not yet been decided how these cases should be treated. Arguing on purely theoretical grounds, which may be fallacious, the best hope of improvement should lie in the early restoration of an adequate blood flow to the kidneys. Caffeine is said to dilate the renal vessels, and although its effectiveness in these cases is doubtful it can certainly be administered in full doses without harm. Giving oxygen in high concentrations might also be of value,...

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“…Because Mateer (9) suggested that the size of the individual might influence the results of the test, we also examined for a.correlation between body weight and the amount of hippuric acid excreted in the urine. We have included, in addition, data on the results of the bromsulphalein test because a difference of opinion (9 to 12) exists in the literature concerning the relative sensitivity of the bromsulphalein and the hippuric acid tests.…”

mentioning

confidence: 99%

The Relation of Hippuric Acid Excretion to the Volume of the Urine 12

Machella

Helm²,

Chornock³

1942

J. Clin. Invest.

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A comparative evaluation of the newer liver function tests

Cited by 43 publications

References 10 publications

The Biliary Excretion of Sulfobromophthalein Sodium (Bsp) in the Rat as a Conjugate of Glycine and Glutamic Acid *†

The Biliary Excretion of Sulfobromophthalein Sodium (Bsp) in the Rat as a Conjugate of Glycine and Glutamic Acid *†

Flocculation Reaction as Test of Liver Function

The Relation of Hippuric Acid Excretion to the Volume of the Urine 12

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