Paul Tasker, FRCS, Harbans Sharma, MSc, PhD, DSc, Joan Braganza, DSc, FRCP. Manchester Royal Infirmary.
INTRODUCTION: Patients with chronic pancreatitis (CP) not on pancreatic extract increased copper excretion in bile in response to intravenous secretin. Serum copper oxidase (caeruloplasmin, ferroxidase I) rose in proportion to the severity of pancreatic insufficiency (PI). Treatment with extract led to low levels of post-secretin biliary copper and serum copper oxidase. The purpose of the study was to determine the influence of exocrine pancreatic insufficiency (EPI) on copper absorption in man.
METHOD: 64Cu absorption was measured by a computerised deconvolution program after separating 64Cu in serial blood samples from that bound to caeruloplasmin by elution through charcoal columns. The method was previously designed, validated, and tested for reproducibility using healthy volunteers.
RESULTS: 10-h absorption from 350-ml water for twelve healthy volunteers was 43.7 (±10.2) % (Mean ± SD) [1.94 ± 0.49%(10h absorption/BMI)]. Excluding three on oral contraceptives (OC+), 64Cu absorption was 42.3 (± 9.7) % (n=9) [or 1.84 ± 0.43 %/BMI]; 6 male, 3 female), and serum copper, caeruloplasmin, and 64Cu-caeruloplasmin and urinary 64Cu were all similar suggesting equivalent copper status on their habitual diet. In nine patients with CP, 10-h absorption was 35.9 (±12.8) %[ 1.71 ± 0.52]; 6 male and three female. Variation increased due to the inclusion of clinical pancreatic insufficiency (CPI) patients, who had pancreatic steatorrhoea. Lower absorption 26.9 (±7.5) % (n=5) [1.33 (± 0.33)] associated more with CPI (t= 4.078, P2 P<0.01) than with vagal transection (VT+) (n=3) (t=3.588, P2 <0.01). Non-CPI patients absorbed 47.2 (±7.3) % (n=4)[2.17 ± 0.18] . Without patients with achlorhydria (DM, DH), the CPI group 10h absorption was still low at 32.1 (± 3.1) % (n=3)[1.57 (± 0.11)]. In the CPI group, the three patients (DH, DM, and NK) had been on long-term supplements (LT+). VT+ (DH, DM, BJ) had lowest absorption; two (DH, DM) with achlorhydria absorbed least. When Nutrizym was combined with oral 64Cu dosein two, DM (total pancreaticoduodenectomy patient) increased his per cent absorption from 18.2 to 40.9% reversing the CPI trend, whereas a non-CPI patient, absorption remained unaltered (42.8 to 40.8%). In this patient cimetidine alone with the dose raised 10h-absorption to 60%. Two patients with primary biliary cirrhosis had 20% 10h absorption irrespective of the type of meal taken. With a protein meal (350 ml 7.14 % casein) 64Cu absorption decreased to 15.8 (±5.6) % in 5 patients with CP compared to 31.4% and 32.1% in controls.
CONCLUSION: The greater decrease in 64Cu absorption in CP with casein was due to both increased Cu status and reduced release of Cu from casein binding. Whereas 64Cu absorption from 350ml water reflected inversely only copper status. There was no evidence of direct inhibition of copper absorption by normal pancreatic secretion in man, but severe EPI appeared to result in decreased 64Cu absorption. On limited data, pancreatic extract appears to normalise absorption not increase it. Further work is needed to confirm this observation. Markers of CPI, such as this test, may be helpful in deciding those patients with EPI, who should be offered pancreatic supplement.