Uneven copper distribution in the human newborn liver

Abstract

The pattern of copper distribution in human newborn liver was investigated by histochemical methods (rhodamine, orcein and rubeanic acid) and by atomic absorption spectroscopy. A significant correlation (p less than 0.005) was found between the degree of histochemical positivity and the copper concentration found by atomic absorption spectroscopy. In the majority of the 30 livers examined (first group), the copper concentration was much higher than that of normal adult liver, although exhibiting striking individual differences. No correlation between the copper content and sex, body weight or gestational age was found. From a second group of five livers, longitudinal tissue slices 0.5 cm thick were partitioned into regular blocks of about 0.5 gm, which were individually analyzed by atomic absorption spectroscopy. Copper appeared unevenly distributed within each liver, with marked differences even between adjacent blocks. However, a consistent tendency of copper to accumulate in the left lobe more than in the right one was evident. Five additional blocks, one for each liver, were further partitioned into 10 small specimens of a final size (0.05 gm), comparable to that of a needle biopsy. Even at this sampling level, consisting of tissue fragments taken from a small tissue area, the copper concentration appeared quite irregularly distributed. These findings may be considered for two different aspects: (a) the biological implications of the pattern of copper accumulation in different lobar and lobular liver compartments and (b) the statistical inference, for diagnostic purposes, of the mean liver copper content from measurements of single percutaneous biopsy specimens.

Histopathologic Variation between Liver Lobes in Dogs

“…To accurately diagnose diffuse liver disease, a biopsy specimen must reliably represent the abnormalities throughout the hepatic parenchyma. In several species important lesions are distributed throughout the liver in consistent relationship with hepatic architecture 3, 4, 5, 6, 7. Whereas a good quality biopsy would be expected to reveal most of these lesions, biopsy collects only a small portion of tissue and error associated with nonhomogenous distribution of disease is possible.…”

“…Whereas a good quality biopsy would be expected to reveal most of these lesions, biopsy collects only a small portion of tissue and error associated with nonhomogenous distribution of disease is possible. In humans, hepatopathies considered diffuse can have unevenly distributed histopathologic changes 3, 4, 5, 6, 7. However, caution must be used when extrapolating results in humans to dogs.…”

Copper-related diseases: From chemistry to molecular pathology

“…Copper concentration in the liver of affected patients normally exceeds 250 mg/kg d.t. (normal values below 50 mg/kg), paralleling the high copper content physiologically observed in newborns [207]. The gene responsible for WD (ATP7B) maps to chromosome 13q14.3; it encodes a protein of 1411 amino acids, a copper transporting P-type ATPase (ATPase7B) and it is highly expressed in the liver, kidney and placenta [8,208].…”

Sources of variance in baseline gene expression in the rodent liver

“…In human infants, iron accumulates more in the left hepatic lobe [69], an effect also seen in iron storage disease in adults [70]. Similarly, copper tends to accumulate more in the left hepatic lobe in newborn human infants [71], while in Wilson's disease more copper accumulates in the right hepatic lobe [72]. In rats treated with the initiating agent diethyl-nitrosamine (DEN), there is a higher incidence of DNA damage and carcinomas in the left and median lobes as compared to the right lobe [73].…”