SURGICAL JAUNDICE

ASPECTS OF PATHOGENESIS AND DIAGNOSIS

H. D. RITCHIE Ch.M., F.R.C.S., F.R.C.S.Ed.
Professor of Surgery, The London Hospital

A DISPASSIONATE REVIEW of our attempts during the past hundred years

to understand the problems of obstructive jaundice might well reach
some rather embarrassing conclusions. This is particularly so with regard to the pathogenesis and diagnosis of the condition, to which I shall
confine my remarks here.
Try as they did, many contributors in these fields seem to have
been unable to avoid retarding progress. Perhaps the first major detour
arose from the work of Ehrlich and van den Bergh. In 18831 the former
showed that bilirubin could be divided into 'indirect' and 'direct' types
on the basis of the diazo reaction. In 19002 the azo-bilirubin compound
was first isolated and studied chemically and spectroscopically by
Proscher, and from these in 1918 van den Bergh3 was able to elaborate
his famous test, which was totally to supersede its less sensitive Gmelin
and Salkowski equivalents.
This led to Barron and Bumstead's classical experiments in 19284
which showed that during the first few hours of biliary obstruction
the van den Bergh test on the blood gave an 'indirect' reaction. This
was followed by the famous 'biphasic response' and some hours later
the reading became 'direct'. To find an explanation for this rapidly
changing picture challenged the ingenuity of some of the most eminent
authorities. For my part I can well remember as an undergraduate
before my final examinations in Edinburgh struggling but failing to
master the explanations available.
The main problem arose from what we might call the van den Bergh
hypothesis, although he did not himself elaborate it as such, that only
bilirubin which has passed through the liver cell and been secreted
into the bile gives the 'direct' reaction. Much confusion stemmed from
this in the clinical situation, and when significant amounts of the pigment present in the blood during what seemed to be a medical jaundice
were found to be direct-reacting, the diagnosis was sometimes

jeopardized.
It was not until the work of Cole, Lathe, and Billing in 19545 that
any clear idea of the reason for this began to emerge. They showed
The 25th Simpson Smith Lecture, West London Hospital

(Anni. Roy. Coll. Surg. Engi. 1973, vol. 52)

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that it was possible by chromatography to separate direct-reacting bilirubin into two distinct moieties, which they designated pigment I and
pigment II. In 1955 Billing6' 7 found that both pigments accumulated
in the serum in obstructive jaundice and in 1956 Billing and Lathe8
showed that pigment II constituted most of the bilirubin in fresh
human bile.
It then only remained for Bollman and Hoffman in 1957 to demonstrate that after hepatectomy direct-reacting pigment I accumulated in
the serum, and the mystery was cleared up. Obviously a direct-reacting

Hours

Fig. 1. Bilirubin concentrations in blood and lymph before and after obstruction of the common bile duct following cholecystectomy.

pigment could be made in the body which had not traversed the liver
and been excreted in the bile. Thus at last the 'van den Bergh hypothesis' was laid to rest and we could move on.
In the meantime, however, a further obstacle was encountered. It was
in 1930 that Rich9 had published his celebrated paper on 'The Pathogenesis of the Forms of Jaundice'. In this he reviewed the available
evidence and attempted a classification of jaundice on the basis of
whether or not the pigment responsible for the icterus had been excreted into the biliary tree. Of the van den Bergh test he wrote, 'I shall
not enter into a description of this now well-known test other than to
mention that when it is applied to bilirubin which has not yet passed
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Ho D. RITCHIE

through the liver cells there occurs a delayed, or so-called indirect

reaction; whereas, in contrast, bilirubin taken from the bile ducts or
from the gall bladder or that regurgitated into the blood from the
bile canaliculi, gives a prompt or direct reaction'. This seems to
have been the first use of the word 'regurgitation', in this sense, in
the literature. He took the view that when the van den Bergh test on
the plasma gave the direct reaction this indicated that whole bile containing bile acids and cholesterol, as well as bilirubin, had been
regurgitated from the biliary tree into liver lymph and the blood stream.
This explanation seemed admirably to fit the observed facts and was
to hold sway for more than 30 years. It contains two major premises.
First that during the course of bile duct obstruction secretion of formed
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bile into the biliary tree continues unchecked. Secondly that it is then
regurgitated or 'vomited back' into the lymph or blood. He went on to
elaborate his subdivision of jaundice into two main types, calling that
variety which results from a primary failure of the liver cells to secrete
bilirubin into the ducts 'retention' jaundice and that which he believed
to be due to passage of formed bile from the biliary tree back into the
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lymph and blood 'regurgitation' jaundice. He did not himself offer any
experimental evidence for these views.
Thirty years later, however, studies during bile duct obstruction
showed a different situation10. It can be seen from Figure 1 that after
24 hours of obstruction all evidence of 'regurgitation', into the fymph at
least, has disappeared. But what of secretion into the biliary tree during
this latter period? Serial analysis of pent-up bile where biliary obstruction had been present for several days gave the required information.
When bromsulphalein, which is handled by the liver in much the same
way as bilirubin, is used as a tracer none of it can be found in bile
from the biliary tree once obstruction has been present for a day or
two (Fig. 2).
And so we now know that during biliary obstruction a short phase
of 'regurgitation' lasting 24 hours ensues, but only in the absence of a
functioning gallbladder. Thereafter and throughout the period of obstruction secretion of bile into the biliary tree does not apparently
occur. Thus in its turn the 'regurgitation' hypothesis of Rich was found
to be suspect and we had to return to the drawing board as it were,
to re-think how we should now subdivide jaundice.
Classifications of jaundice abound in the literature. Some have served
a useful purpose, others have not. Table I shows four of the best known
of these. The pathological classification of McNee in the top left-hand
corner is still widely used and serves to remind particularly the
undergraduate of the main causes. It is, however, in difficulty when, for
example, the cholestatic variety of viral hepatitis is being considered.
TABLE I
TYPES OF JAUNDICE
Rich
McNee
"Retention"
Haemolytic
"Regurgitation"
Toxic or infective

Obstructive

Prehepatic
Hepatic
Posthepatic

N. American
Medical

Surgical

Most surgeons now tend to approach the problem by asking whether

these people need an operation or not. The simplicity of the North
American classification speaks for itself and, for the surgeon, it is perhaps to be preferred to its predecessors because of the emphasis it puts
on therapy. Here again, however, we have met with waming signs.
Alarming reports of the dangers of mistakenly operating on patients
whose jaundice is due to viral hepatitis appeared in the literature. Shaldon and Sherlock in 195711, Datta et al. in 196312 and Turner and
Sherlock in 196413 painted a grim picture of the outcome. The latter re257

IL D. RITCHIE

ported a personal experience of 12 patients of whom 5 died within 4

weeks of operation, while 4 of the remainder had a protracted illness
with ascites. They gave no further details. As a substitute for surgery
in cases where the diagnosis was in doubt they have advised a sort of
'medical laparotomy' employing the steroid diagnostic test, liver biopsy,
or percutaneous cholangiography on the grounds that these procedures
are safer.
These strictures prompted an analysis of the results of surgery in
jaundiced cases at The London Hospital. We tried to ascertain how
many 'mistaken laparotomies' our surgeons had been making for jaundice and how many patients were in fact having operations during an
attack of viral hepatitis. Of 152 laparotomies for jaundice performed
during the 5-year period studied, 3 (2%) were 'mistaken'. The jaundice
was due to viral hepatitis in 2 of these cases and to a drug in one. All
3 patients survived (Table II).
Similarly, in a much larger series published in 1963 by Harville and
Summerskill14 from the Mayo Clinic the jaundice was found to be
medical in origin in 1.7% of cases. The mortality in this series from
operating in the presence of hepatocellular disease can be calculated
TABLE II
COMPARATIVE MORTALITY FROM "MISTAKEN" LAPAROTOMY AND PERCUTANEOUS
LIVER BIOPSY
Mortality from percutaneous liver
Mortality from "mistaken" laparotomy
biopsy (Zamcheck &
for jaundice
Klausenstock15).
Mayo Clinic14
London Hospital

(1961-1965)
NIL

(1950-1961)
0.14%

0.17%

to have been 0.14% of 2,800 laparotomies in jaundiced patients (Table

II). This may be compared with a mortality of 0.17% in 20,000 liver
biopsies on anicteric patients reported by Zamchek and Klausenstock'5
in 1953, this being one of the procedures advocated to avoid the risks
of surgical laparotomy. These authors noted that the risk of liver biopsy
was higher in jaundiced patients and this has been our experience.
Thus it became clear that in cases where the diagnosis continued to
be in doubt timely laparotomy was to be preferred to most of the
investigative extravaganzas which had been developed to avoid it. In
our experience the risks of procrastination may be as great as those of
undue urgency. If after 5-6 weeks of jaundice the diagnosis has not
become clear we believe that laparotomy is indicated.
But how are we to diagnose a surgical jaundice earlier than this?
Our experience with percutaneous cholangiography had not suggested
that it was free from risk. The method consists in introducing a long
needle through the skin into the liver in an attempt to puncture a dilated
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duct. If this is done bile is aspirated and radio-opaque dye injected.

The only lesion which can be identified with certainty by this technique
is an extrahepatic obstruction'6. It cannot finally exclude this,14' 17, 18
since if the needle fails to enter a duct nothing is seen on subsequent
radiology. Biliary peritonitis and haemoperitoneum may follow the
procedure"9, 20. That most people using the technique have a surgeon
standing by to perform laparotomy may be regarded as testimony to
the general awareness of these hazards.
Our search for a less risky method has led us to use a combination
of tests performed by passing a tube through the mouth into the duodenum. This enables us to test pancreatic function, look in the duodenal
juice for neoplastic cells, and finally to have a duodenogram carried out
by the radiologist. As in all investigative work of this type we find that
experienced nursing personnel achieve the best cooperation from the
patients and the most reliable results from the tests. I should like here
to recognize the work done by two London Hospital Sisters, Sister Miss
Keenan and Sister Mrs. Barrah, who do these tests in our Gastrointestinal Investigation Unit.
We have performed some 300 of these tests and find them a useful
adjunct to the early diagnosis of lesions in the pancreas or duodenum
or at the ampulla. They will not, however, demonstrate stones in the
common bile duct or a high bile duct carcinoma, although occasionally
cell cytology may reveal this. In jaundiced patients they seem to be particularly helpful. During a 3-year period recently we have had the
opportunity to study 75 patients21. The diagnosis in these cases was
confirmed at operation or from the subsequent clinical course, which
now extends from 1 to 3 years. If the surgeon had accepted the findings of these tests, laparotomy would have been indicated in 40 of
these patients. This would have been correct in 39. In the 40th patient
intrahepatic secondaries from a previously excised colonic carcinoma
were present. In the remaining 35 patients no evidence of a lesion in the
pancreas or duodenum or at the ampulla was demonstrated. Here again
with one exception the combined findings of the three tests were correct. A carcinoma near the neck of the pancreas obstructing the common
bile duct was missed. In fact, in this series of 75 patients all but one
of the carcinomas of the pancreas and all the ampullary tumours were
diagnosed by the tests (Table III).
TABLE III
TRIPLE TEST FINDINGS IN 75 JAUNDICED PATIENTS
1. All but one of the carcinomas of the pancreas (29) and all ampullary
tumours were diagnosed by the tests.
2. No case of 'medical' jaundice gave a positive result.
3. Tests do not demonstrate:
stones in the common bile duct.

high bile duct neoplasms.

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IL D. RITCHIE

We must bear in mind, however, that while these tests may help
us to avoid laparotomy in medical jaundice they do not solve all our
problems in the diagnosis of obstructive jaundice. They will not demonstrate stones in the common bile duct or high bile duct neoplasms, but
here the need for early operation is perhaps less.
This then would appear to be a safe method of expediting the diagnosis of certain types of jaundice. But many problems remain. So often
in jaundice due to panpreatic carcinoma, for example, the surgeon finds
the lesion too far advanced to be able to do more than a palliative
operation.
In reviewing the whole field, however, we may be reassured by the
knowledge that once more we are moving forward, and in the words
of Horace: 'Quad optanti divom promittere nemo auderet volvenda
dies en attulit ultro'-'What no one of the Gods would dare to promise
in answer to our prayers-lo, time itself as it rolls its course, has accomplished for us' !
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REFERENCES
EHRLICH, P. (1883) Quoted by van den Bergh (ref. 3).
PROSCHER, -. (1900) Quoted by van den Bergh (ref. 3).
VAN DEN BERGH, H. A. (1918). Die Gallenfarbstoff im Blute. Leiden, van Doesburgh.
BARRON, E. S. G., and BUMSTEAD, J. H. (1928) J. exp. Med., 47,999.
COLE, P. G., LATHE, G. H., and BILLING, B. H. (1954) Biochem. J., 57, 514.
BILLING, B. H. (1955) J. clin. Path. 8, 126.
BILLING, B. H. (1955) J. clin. Path.. 8, 130.
BILLING, B. H., and LATHE, G. H. (1956) Biochem. J., 63, vi.
RICH, A. R. (1930) Johns Hopk. Hosp. Bull., 47, 338.
RITCHIE, H. D. (1959). Ch.M. Thesis University of Edinburgh.
SHALDON, S., and SHERLOCK, S. (1957) Brit. med. J., 2, 734.
DATTA, D. V., SHERLOCK, S., and SCHEUER, P. J. (1963) Gut, 4, 223.
TURNER, M. D., and SHERLOCK, S. (1964). In Surgery of the Gall Bladder and Bile Ducts, ed. R. Smith
and S. Sherlock. London, Butterworths.
HARVILLE, D. D., and SUMMERSKILL, W. H. J. (1963) J. Amer. med. Ass., 194,257.
ZAMCHEK, M., and KLAUSENSTOCK, 0. (1953). New Engl. J. Med., 249, 1062.
GEORGE, P., YOUNG, W. B., WALKER J. G., and SHERLOCK, S. (1965) Brit. J. Surg., 52, 779.
GEORGE, P. (1966). In Postgraduate Gastroenterology, ed. T. J. Thompson and I. E. Gillespie. London,
Bailli6re.
THORBJARNARSON, B. (1967) Surgery, 61, 347.
GLENN, F., EVANS, J. A., MUJAHED, Z., and THORBJARNARSON, B. (1962) Ann. Surg., 156, 451.
THORBJARNARSON, B., MUJAHED, Z., and GLENN, F. (1967) Ann. Surg., 165, 33.
BOURKE, J. B., SWANN, J. C., BROWN, C. L., and RITCHIE, H. D. (1972) Lancet, 1, 605.

HAMILTON BAILEY PRIZE

APPLICATIONS ARE NOW invited by the British Section of the International College of Surgeons for the third Hamilton Bailey Prize. This is a travelling
scholarship worth 750, and consultants or senior registrars in surgery, radiology,
or anaesthetics may apply. Applications should be sent to the Secretary of the
British Section, Royal Northern Hospital, Holloway Road, London, N.7, not
later than 31st May 1973.

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