Experimental Enterogenous Cyanosis and Anaemia

Abstract

Rats with jejunal pouches develop an anaemia which is partially haemolytic in nature and accompanied by small amounts of methaemoglobin (MHb) and sulphaemoglobin (SHb). These pigments increase upon sterile incubation of the blood. The presence of these abnormal pigments indicates that oxidative damage has occurred. Most of the abnormalities improve on feeding neomycin. Rats with blind pouches are more sensitive than normal rats to the oxidant effects of phenacetin on RBCs. RBCs incubated in urine from rats with pouches developed more MHb than RBCs incubated in urine from normal rats. We conclude that bacterial overgrowth in the intestine, by means yet undetermined, can cause oxidative damage to RBCs and that this effect can be produced by constituents of the urine of rats with pouches. This toxic effect of bacterial overgrowth may condition RBCs to oxidant drug damage.The term 'enterogenous cyanosis' was applied by earlier workers to patients with methaemoglobinaemia and sulphaemoglobinaemia purportedly caused by absorption of endogenously produced nitrites and sulphides from an abnormally functioning intestine. These cases were reviewed (Finch, 1948) and it was emphasized that many of these patients were taking analgesic drugs and that the intestinal disease may have been contributory but not the sole cause for methaemoglobin (MHb) and sulphaemoglobin (SHb) production in these patients.Recent data support this view since oxidant drug metabolites were found in the urine of patients with cryptic analgesic abuse (Azen et a2, 1970), one of whom had chronic methaemoglobinaemia and a decrease of this pigment when treated with neomycin (Rossi et al,,1966). Other studies in animals (Canellos et al, 1967) and man (Selwyn, 1955;Hutchison et al, 1962) suggest that gastrointestinal disorders, especially those associated with bacterial overgrowth, may enhance susceptibility of RBCs to oxidant drug stress. However, it has not been clearly demonstrated in animals or man that 'enterogenous cyanosis' may be produced by gastrointestinal abnormalities alone. In this paper, we have shown that rats with blind loops develop haemolytic anaemia, accompanied by methaemoglobinaemia, sulphaemoglobinaemia and urinary excretion of oxidant substances. Furthermore, the red cells of the.ie animals demonstrate increased susceptibility to the effects of oxidant drugs. MATERIALS AND METHODSOperative procedures. 'Self-filling' jejunal blind pouches (Cameron et al, 1949) about 8 cm

Vitamin E and Oxidative Damage by Tryptophan Metabolites in Experimental Enterogenous Cyanosis and Anaemia

“…The only significant findings were that the spleens and, to a lesser extent, the livers of animals with pouches showed more congestion. This is in keeping with our previous data (Westphal & Azen, 1972) which showed significant splenomegaly in pouched animals. No light-microscopic changes in renal tubular cells were noted.…”

“…In a previous study (Westphal & Azen, 1972) we demonstrated that bacterial Overgrowth alone, in rats with jejunal pouches, could produce small amounts of methaemoglobin and sulphaemoglobin and a liaemolytic anaemia. Doses of phenacetin not affecting control animals produced cyanotic levels of these pigments and Heinz bodies in the RBC of rats with jejunal pouches.…”

“…H & E sections of liver, spleen and kidney were examined by the author and then submitted 'blind' to an experienced pathologist. The main purpose of these studies was to look for 'oxidative damage' to cells other than the RBC, as was previously noted (Westphal & Azen, 1972). The only significant findings were that the spleens and, to a lesser extent, the livers of animals with pouches showed more congestion.…”

“…In a previous article (Westphal & Azen, 1972) it was shown that rats with jejunal pouches develop an anaemia which is partially haemolytic in nature, that small amounts of metliaenioglobin and sulpliaemoglobin appear in the blood, that these abnormalities improve on feeding neoniycin, that such animals are more sensitive than controls to the oxidant effects of phenacetin on red cells and that the urine contains oxidative activity for haemoglobin. It was noted that 'enterogenous cyanosis' (Finch, 1948;Rossi et al, 1966; Azen et al, 1970) in humans was most likely due to analgesic abuse in patients with or without intestinal bacterial overgrowth, but that the bacterial overgrowth alone had some oxidative effects on haemoglobin, at least in animals.…”

A newborn with cyanosis

“…They also excreted urine containing material with oxidant eects on red blood cells. The authors con®rmed that intestinal bacterial overgrowth played a key part in the above mentioned constellation of problems and hypothesized that vitamin E may also be implicated in its pathogenesis [14].…”