Gut, 1969, 10, 623-627

Studies in obstructive jaundiceW. B. CONOLLY, F. 0. BELZER, AND J. E. DUNPHY

From the Departments of Surgery, University of California School of Medicine, and San FranciscoGeneral Hospital, San Francisco, California

SUMMARY Acute obstruction of the extrahepatic ducts causes gross proximal duct dilatation, andelevated levels of ornithine carbamyl transferase, bilirubin, and alkaline phosphatase.

Slow progressive obstruction causes variable proximal duct dilatation and in these cases bilirubin,alkaline phosphatase, and ornithine carbamyl transferase return to normal, despite the presence ofsevere though incomplete obstruction of the common duct and microscopic findings of biliarycirrhosis. In the early phases, ornithine carbamyl transferase is a slightly more sensitive indicator ofbiliary obstruction than alkaline phosphatase or bilirubin, but the values still return to normal inthe face of a persistent stricture.

If a patient who has previously had common duct surgery develops recurrent episodes of feverwhich suggest cholangitis, it should be assumed that he has a recurrent stricture, even though a

cholangiogram and liver function may be normal or only slightly altered. A delay until the liverfunction studies show consistently raised levels may result in severe biliary cirrhosis and decreasedhepatic reserve.

Stricture of the extrahepatic ducts can be difficult todiagnose because the patient may feel well, and theliver enzymes may be normal or only slightly elevated.Delaying operation, however, until the bilirubin andalkaline phosphatase levels are consistently elevatedmay result in a cirrhotic liver and diminishedhepatic reserve.

Ornithine carbamyl transferase is an enzymefound predominantly in the mammalian liver.Reichard (1957) described a method for its esti-mation and determined its activity in the serum of695 patients (1962). Jonson and Reichard (1963)compared ornithine carbamyl transferase, alkalinephosphatase, and bilirubin in acute extrahepaticbiliary obstruction of dogs and concluded thatornithine carbamyl transferase activity was a moresensitive index of biliary obstruction than that ofalkaline phosphatase or bilirubin. Their studyconsisted of 10-hour experiments.

This study compares ornithine carbamyl trans-ferase values with bilirubin and alkaline phosphatasein extrahepatic obstruction of the biliary tract over athree-month period, and relates them to cholangio-grams and liver biopsies.

MATERIALS AND METHODS

Obstructive jaundice was produced in eight 20-kg goats byplacing an ameroid constrictor (3.5 mm, internal dia-

meter) around the hepatic or common bile ducts. Venousblood samples were taken from the jugular vein beforeoperation, and three times weekly until the goats becamejaundiced. The blood was tested in each sample forbilirubin, alkaline phosphatase, and ornithine carbamyltransferase. Liver biopsies were taken before placingthe constrictors during postoperative cholangiography.The goats were divided into three groups. Group 1 (onegoat) had bilirubin, alkaline phosphatase, and ornithinecarbamyl transferase tests three times a week for fiveweeks for control studies. Group 2 (four goats, nos. 2, 3,4, and 5) had water-sterilized ameroid constrictors placedaround the common bile duct to produce rapid obstruc-tion. In group 3 (four goats, nos. 6, 7, 8, and 9), slowobstruction was produced by placing an oil-sterilizedameroid constrictor around the common or hepaticducts.

If the goats became severely jaundiced they were killedand cholangiograms and liver biopsies were performed.In goats without jaundice, re-exploration was performedafter eight weeks and cholangiograms and liver biopsieswere obtained.

RESULTS

GROUP 1 (CONTROL) The values for bilirubin wereconsistently less than 0-1 mg/100 ml, alkalinephosphatase ranged between 2 and 4 Bodanskyunits/100 ml, and ornithine carbamyl transferasebetween 0-1 and 0 25 Reichard units/100 ml (Fig. la).

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W. B. Conolly, F. 0. Belzer, and J. E. Dunphy

ALKALINEPHOSPHATASE(BODANSKYUNITS)

BILIRUUBIN(mg9 PER CENT)

03 -

0.2-0.1 - o-°1"0 ,o_0 , ..

%.0o~ oqb0-

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FIG. 1. enzyme and bilirubinvalues: (a) normal goat (group1); (b) acute obstructive jaundice(group 2); (c) chronic obstructivejaundice (group 3).

04-ORNITHINECARBAAMYL OB-TRANSFERASE 02-REICHARD~~1UNITS) 0.1 3

1 2 3 4 5*MICROMOLES AMMONIAPER SrmI. OP SERUMIN 2-4 HOURS

WEEKSFIG. 1 a.

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ORNITHINE 2'S-CARBAMYL -

( TRANSFERASE 1-5-* REICHARD UNIT5 ) 1.0_

O- I*MICROMOLES AMMONIA P*5ml Or SERUM IN 24 HA

ORNITHINECARBAMYL

(TQANSFEQASE( REICHAWL0 UN ITS)20 -CONSTRICTOQR

PLACED ONCOMMON BILEDucT

P0- EBILIRU IN(m9. ~/o)

0 .2 .z.it0.3]

0 WNORA

BILI RUBIN(rn9°b) ALKALINE6 CONSTrRIC7t PHOSPHATASE

ON COMMON 7 (BODANSKYBILE DUCT OC UNITS)

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*MICROMOLES AMMONIA WEEKSPER 5 m/. OpF SERUMIN 24 HOUPS

FIG. lc.

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Studies in obstructive jaundice

FIG. 2. Liver biopsy one week after acute ameroid conistriction of common bile duct. Note cholestasisand cholangitis.

GROUP 2 (RAPID OBSTRUCTION) Jaundice occurredwithin 10 to 14 days. The bilirubin and the ornithinecarbamyl transferase became progressively elevated.The elevation of alkaline phosphatase was slowerand showed moderate variation at times (Fig. lb).Liver biopsies showed substantial dilatation of theintrahepatic ducts and microscopic studies showedcholestasis and cholangitis (Fig. 2).

GROUP 3 (SLOW OBSTRUCTION) These four animalswere studied for three months. The bilirubin, alkalinephosphatase, and ornithine carbamyl transferaselevels were raised in the early postoperative period(Fig. Ic). They then slowly returned to normal levels,but rose again after cholangiography. Normalenzymes were formed in spite of constricted extra-hepatic ducts, and biliary stasis was seen on micro-scopic examination (Fig. 3).

Intrahepatic duct dilatation appeared to bedirectly related to the rapidity and degree ofobstruction.

DISCUSSION

Jonson and Reichard (1963) showed that partialobstruction of the common bile duct resulted inincreased ornithine carbamyl transferase levels atlower biliary pressures than were required to elevatethe bilirubin or alkaline phosphatase. They con-cluded that ornithine carbamyl transferase activityappeared to be a more sensitive index of incompletebiliary obstruction than either alkaline phosphataseor bilirubin. In our studies, however, we were unableto show any advantage in the ornithine carbamyltransferase determinations over the routine bilirubinand alkaline phosphatase values. In acute obstructionthe ornithine carbamyl transferase increased con-sistently as did the bilirubin. The rise in alkalinephosphatase was sometimes minimal and delayed.The ornithine carbamyl transferase appeared to havelittle value in these situations of rapid and completeobstruction; the bilirubin is reliable and far easier toestimate. In slow, progressive obstruction, the orni-

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FIG. 3. Liver biopsy following three months of chronicameroid constriction of the common bile duct. Note peri-portal cholangitis.

FIG. 4. Cholangiogram of goat no. 9 (following threemonths of chronic ameroid constriction). A clamp wasnecessary to force dye proximal to the constrictor.

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Studies in obstructive jaundice 627

thine carbamyl transferase increased to abnormallevels about three days before the bilirubin oralkaline phosphatase rose but returned to normal inabout five weeks. However, it remained normaldespite severe, though incomplete, obstruction of theextrahepatic duct.

It is commonly assumed that dilatation occursproximal to bile duct constriction, either by stricture,neoplasms, stones, or oedema from severe pan-creatitis. Radiographs taken during these experi-ments showed that dilatation occurred only when aconstriction was complete enough to prevent freeflow of bile. The common bile duct of goat no. 9(Fig. 4) was constricted from 4 mm to 05 mm with-out proximal dilatation. Dye, however, did not crossthe obstruction at the time of cholangiography, until

the distal common biliary duct was occluded butmicroscopic examination of this liver showedchanges of early biliary cirrhosis. The pathologicalsequelae of extrahepatic duct obstruction arecholestasis, cholangitis, portal cirrhosis, and biliarycirrhosis. Early changes can be seen in the liver, evenin the presence of normal enzymes, and cholangio-graphic evidence of ducts of normal size.

REFERENCES

Jonson, G., and Reichard, H. (1963). Ornithine carbamoyl transfer-ase activity in blood plasma in partial obstruction of thecommon bile duct. Acta chir. scand., 126, 123-132.

Reichard, H. (1957). A new specific liver test. Determination of orni-thine carbamyl transferase in human serum. Scand. J. clin.Lab. Invest., 9, 103-104.

-(1962). Serum ornithine carbamoyl transferase activity in man.A highly specific test of liver and biliary tract involvementObservation on 695 patients. Acta med. scand., 172, 723-738.

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