Download The Measurement of Biliary Copper Secretion in Humans

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Medical Research Society
Solutes which penetrate cell membranes poorly, such
as mannitol, if administered intravascularly as hypertonic solutions, will osmotically shrink the swollen
cells, terminate the ‘no-reflow’ and allow prompt
return of blood flow. This reduces the ischaemic injury
to the tissue and protects the organ from functional
failure.
COMMUNICATIONS
1. THE MEASUREMENT OF BILIARY COPPER
SECRETION I N HUMANS
D. J. FROMMER
Department of Medicine, Royal Free Hospital
Wilson’s disease is characterized by the accumulation
of copper in the body, the toxic action of which is
believed to be responsible for the hepatic, cerebral
and other manifestations. Copper is absorbed by the
upper small intestine, concentrated in the liver and
incorporated into caeruloplasmin or excreted from
the body via the biliary system and the gastrointestinal
tract. The cause of the accumulation of copper,
especially in the liver, in Wilson’s disease is uncertain.
Using 64Cu or 67Cu various workers have found
evidence for increased absorption or decreased excretion in the intestine.
The biliary secretion of copper into the duodenum
was measured in eight patients with Wilson’s disease
(three were untreated, with hepatic dysfunction) and
ten control subjects (three with hepatic dysfunction).
The method of Go et al. (1970, Gastroenterology, 58,
321) was used with the modification of omitting a
gastric marker. A multi-lumen tube was passed into
the duodenum so that juice was aspirated at the
duodeno-jejunal junction while the duodenum was
perfused at 5 ml/min with an amino-acid solution containing a non-absorbed marker W r C1,. Gastric
juice was also aspirated. Collecting periods of 20 min
were used and the perfusions were continued for 2-3
h. Copper concentrations of the aspirate were
measured by wet ashing of the samples and extracting with zinc dibenzyldithiocarbamate.
The secretion of copper was calculated from the
following equation:
The mean concentration of copper in the duodenal
aspirate in Wilson’s disease, 7.6k0.6 pg/100 ml
(SEM, n = 48), was significantly lower than that in
the control group, 16-8k1.4 pg/100 ml (n = 73,
P < 0.001). The mean biliary copper secretion rate in
the Wilson’s disease patients, 8.6+0.8 pg/20 min
(n = 47), was also significantly(P<O.001) below that
of the control patients, 16-4kO.8pg/20 rnin (n = 74).
The presence of liver dysfunction made no significant
difference to the secretion rates in either group of
patients.
These results suggest that in Wilson’s disease the
liver is unable to secrete copper in adequate amounts
into bile leading to an accumulation of copper within
the body.
2. THE EFFECT O F RETICULOENDOTHELIAL
BLOCKADE ON HEPATIC PHAGOCYTOSIS
AND THE IMMUNE RESPONSE
R. L. SOUHAMI
Department of Experimental Pathology, St Mary’s
Hospital Medical School, and Department of Clinical
Haematology, University College Hospital Medical
School
(Introduced by E. R. HUEHNS)
In normal mice SO-SO% of 51Cr-labelled sheep red
blood cells (sheep RBC), injected intravenously, are
localized in the liver and 2-5% in the spleen. In the
experiments to be described, blockade of the reticuloendothelial system was induced by a single intravenous
injection of colloidal carbon. The effect of blockade
was to depress the hepatic uptake of sheep RBC to
only 10% of the injected dose. The suppression of
hepatic uptake began within 5 rnin after the blockading injection, and had reached a maximum by 6 h.
The suppression of hepatic uptake of sheep RBC
was accompanied by a marked increase of splenic
uptake (to 40% of the injected dose). regardless of
the dose of sheep RBC. This redistribution of sheep
RBC from liver to spleen was accompanied by an
increased production of humoral antibody in blockaded mice, and an increase in numbers of antibody
forming cells in the spleen. The ‘stimulation’ of the
immune response could be accounted for entirely by
CuoxS1Crlx V ,
the redistribution of antigen.
cu, =
Recovery from blockade took place over 4 days
CrD
and this recovery process was prevented by irradiation
where Cu, = copper secreted in pg/20 min period
with X-rays. Labelling with 3H-thymidine during
CuD = copper content in pg of 1 ml of duo- recovery from blockade demonstrated large numbers
denal aspirate
of labelled Kupffer cells in the liver. Animals which
CrD = SICr C13 content of 1 ml duodenal were irradiated, but whose bone marrow was shielded,
aspirate
recovered normally from blockade.
Crl = 51CrC13 content of 1 ml perfusing fluid
These results suggest that an increased immune
V 1 = volume of fluid perfusing duodenum response occurs when the hepatic sequestration of a
over 20 min
particulate antigen is prevented. This mechanism may
The recovery of marker in the duodenal aspirate in play a part in producing hypergammaglobulinaemia
the two groups of patients did not differ significantly. in cirrhosis of the liver and other liver diseases. The