ABSTRACT
1. Chronic hypoxia enhances intestinal iron transport but the cellular processes involved are poorly understood. In order to assess the effects of 3 days of hypoxia on iron uptake across the duodenal brush-border membrane, we have measured the membrane potential difference (Vm) of villus-attached enterocytes by direct microelectrode impalement and have used semi-quantitative autoradiography to study changes in expression of iron uptake during enterocyte maturation. 2. Hypoxia increased duodenal Vm (-57.7 vs. -49.3 mV, P < 0.001). Ion substitution experiments revealed that hyperpolarization was due, at least in part, to a reduction in brush-border Na+ permeability. 3. Autoradiography revealed that hypoxia increased by 6-fold the rate of iron accumulation during enterocyte transit along the lower villus and enhanced by 3-fold the maximal accumulation of iron. Depolarization of the brush border, using a high-K(+)-containing buffer, caused a proportionally greater reduction in iron uptake in control compared with hypoxic tissue suggesting that the raised iron uptake is only partly driven by brush-border hyperpolarization. 4. We conclude that hypoxia increases the expression of iron transport in duodenal brush-border membrane and an enhanced electrical driving force may be involved in this response.
Subject(s)
Duodenum/blood supply , Duodenum/metabolism , Hypoxia/physiopathology , Iron/pharmacokinetics , Animals , Autoradiography , Duodenum/ultrastructure , Hematocrit , Hemoglobins , Hypoxia/metabolism , Intestinal Mucosa/chemistry , Intestinal Mucosa/metabolism , Iron/analysis , Male , Membrane Potentials/physiology , Microvilli/chemistry , Microvilli/metabolism , Rats , Rats, WistarABSTRACT
Haemolytic anaemia induced by phenylhydrazine (PZ) promotes iron absorption across rat small intestine. This present study investigates the role of the brush border potential difference (Vm) and mucosal reducing activity in the response. In addition, quantitative autoradiography was used to assess PZ-induced changes in the villus localization of brush border iron uptake. Iron transfer from duodenum to blood was increased significantly 5 days after treatment with PZ. Autoradiography showed that most brush border iron uptake occurred at the upper villus region and the maximal rate was increased fourfold by PZ. Duodenal villus length was increased in PZ-treated rats. PZ treatment did not influence mucosal reducing activity but Vm, measured using duodenal sheets, increased from -50 to -57 mV (P < 0.001) and this was due to a reduced brush border sodium permeability. Thus, an expanded absorptive surface and an enhanced electrical driving force for iron uptake across the duodenal brush border are important adaptations for increased iron absorption in PZ-induced haemolytic anaemia.
Subject(s)
Anemia, Hemolytic/metabolism , Duodenum/metabolism , Intestinal Absorption/physiology , Iron/pharmacokinetics , Anemia, Hemolytic/chemically induced , Animals , Disease Models, Animal , Duodenum/drug effects , Duodenum/ultrastructure , Intestinal Absorption/drug effects , Iron/blood , Male , Membrane Potentials/drug effects , Microvilli/metabolism , Phenylhydrazines , Rats , Rats, Sprague-DawleyABSTRACT
A case of a middle aged woman with weight loss, ascites, and a pleural effusion is presented where a clinical diagnosis of ovarian cancer was made. Her CA 125 was greatly increased at 873 IU/ml and the ascites was a lymphocytic exudate but cytology failed to show malignant cells. Operative biopsy showed numerous noncaseating granulomas in the omentum but no mycobacterial organisms were seen. Empiric antituberculous treatment was started before positive culture results were received and when treatment had ended both the ascites and pleural effusion had resolved and the CA 125 had fallen to 7 IU/ml. Review of published works showed several other examples of tuberculous peritonitis associated with increased CA 125 and the possible cause of raised CA 125 in this condition is discussed.