Measurement of Gastrointestinal Protein Loss Using Ceruloplasmin Labeled with 67Copper*

Abstract

Summary. Ceruloplasmin labeled with 67copper and administered intravenously to dogs, control human subjects, and patients with excessive gastrointestinal loss was shown to fulfill the requirements for a label for quantification of gastrointestinal protein loss. The radiocopper moiety was poorly absorbed from the gastrointestinal tract, not actively secreted into the intestinal tract, and did not alter significantly the metabolism of ceruloplasmin. Approximately 70% of the body pool of ceruloplasmin in both dog and man was within the intravascular space. In control human subjects the mean ceruloplasmin concentration was 30 mg per 100 ml with total circulating and total body ceruloplasmin pools of 15.5 and 22 mg per kg, respectively. In patients with excessive gastrointestinal protein loss secondary to intestinal lymphangiectasia, the serum ceruloplasmin concentration was reduced to 16 mg per 100 ml with a comparable reduction in the total circulating and total body ceruloplasmin pools to 8.8 and 12 mg per kg.The survival.half-time of ceruloplasmin was 6.1 days in normal human subjects and 4.5 days in normal dogs. From 1.0 to 1.9% of the intravascular pool of ceruloplasmin was lost into the gastrointestinal tract of the dog per day, representing less than 11% of the over-all metabolism of this protein.In control human subjects from 1.9 to 3.9% of the intravascular pool was lost into the gastrointestinal tract each day, representing a maximum of from 11 to 22% of the over-all metabolism of this molecule. In contrast, patients with intestinal lymphangiectasia had a markedly shortened ceruloplasmin survival of 3.1 days, with from 15 to 40% of the intravascular pool of ceruloplasmin cleared into the gastrointestinal tract daily. This represented 76% of the over-all metabolism of this protein. Thus, although bulk loss of serum proteins into the gastrointestinal tract does not normally appear to be a significant factor in protein metabolism in normal dogs and men, such loss is a major factor in the pathogenesis of the hypoceruloplasminemia noted in patients with intestinal lymphangiectasia.

Intestinal Lymphangiectasia: a Protein-Losing Enteropathy with Hypogammaglobulinemia, Lymphocytopenia and Impaired Homograft Rejection*

“…shortened immunoglobulin survivals). The increased fractional catabolic rates were presumably due to excessive loss of immunoglobulins into the gastrointestinal tract since these patients with intestinal lymphangiectasia were shown with albumin-51Cr and ceruloplasmin-67Cu to lose from 5 to 50% of their intravenous protein pool into the gastroinestinal tract daily as compared with 0.5-2.0%o in control subjects (20,21). In spite of the reduced serum immunoglobulin levels, synthetic rates were not compensatorily increased.…”

95Nb-labelled Albumin for the Study of Gastrointestinal Albumin Loss

“…The only other labelled protein which measures both gastrointestinal leakage and metabolic turnover is 67Cu-ceruloplasmin (Waldmann, Morell, Wochner, Strober & Sternlieb 1967). However, this compound is expensive, the isotope is shortlived (T % of 67Cu: 62 hours), and turnover data are obtained only on ceruloplasmin and not on albumin, i.e.…”

Protein-Losing Enteropathies

“…Despite these advantages, 67 Cu-labeled ceruloplasmin proved impractical for the routine measurement of PLE because of its expense and because 67 Cu has a short half-life. However, studies of PLE using this substance were useful because it established that no more than 10% of the total catabolism of a serum protein in normal individuals is due to the loss of the protein into the GI tract; as we shall see, this provides validation of the values for normal GI excretion of intact protein obtained with other methods of measuring GI protein loss ( Waldmann et al, 1967a).…”

“…However, the substance is a totally nonphysiologic molecule whose metabolism in the body does not reflect serum protein metabolism and whose secretion into the GI tract does not accurately quantify PLE, if such is occurring. By contrast, a second substance, 67 Cu-labeled ceruloplasmin, is an excellent material for the measurement of PLE because the labeled copper moiety is a natural and intrinsic part of the serum protein to which it is bound (ceruloplasmin) and because labeled copper fulfills the requirements outlined earlier for an ideal substance with which to measure PLE (Waldmann et al, 1967a). Despite these advantages, 67 Cu-labeled ceruloplasmin proved impractical for the routine measurement of PLE because of its expense and because 67 Cu has a short half-life.…”