Pigment metabolism and renal failure in acute sulphonamide haemolysis resembling blackwater fever

Field: Medicine (Health Sciences)

1. Attention is directed to the resemblances and differences in blood pigment metabolism in such conditions as blackwater fever, haemolytic jaundice, and the intravascular haemolysis that sometimes occurs after sulphonamides. It is noted that intracorpuscular methaemoglobin occurs after sulphonamides, plasmoquine and acetanilide, but does not occur in blackwater fever so far as is known. Oxyhaemoglobin, methaemalbumin and haemobilirubin are common to all of the intravascular haemolyses. It appears that p-aminophenol or a derivative thereof is responsible for the methaemoglobinaemia that occurs after aniline and acetanilide, whether or not similar metabolites are responsible in the case of sulphonamides and plasmoquine seems uncertain. 2. In the present case there was an acute massive intravascular haemolysis accompanied by the presence of plasma oxyhaemoglobin, methaemalbumin, and haemobilirubin, as well as intracorpuscular methaemoglobin, and a profound fall in the red cell count. 3. Urinary methaemoglobin may be present in the intravascular haemolyses, but its presence in the urine is not related to plasma methaemalbumin, or intracorpuscular methaemoglobin; nor is its formation entirely dependent upon urinary pH or ionic concentration. In the present case both oxyhaemoglobin and methaemoglobin were found in the urine. As often in these haemolyses there was in this case an almost complete anuria, that was not associated with blockage of the renal tubules with precipitated products of haemoglobin. There were, however, changes in both the tubules and the glomeruli, such as are characteristic in blackwater fever, and incompatible transfusions. 4. It is suggested that these changes, the anuria and azotemia, are secondary to more fundamental ones that occur in the blood stream and which lead to upsets in glomerular filtration, tubular reabsorption, anuria and azotemia, and that any blockage that occurs is a secondary phenomenon due to antecedent causes, of which no single one can be specifically incriminated. 5. In the present case there was a great difference in the histological appearance of the kidney tubules and glomeruli in the paraffin and frozen material. In the paraffin sections the sub-capsular spaces and glomerular tufts appeared normal and the tubules much dilated, with debris suspended freely in their lumina. In the frozen material, on the other hand, the capsular spaces were almost non-existent, and the glomerular tufts filled almost the whole of the space. The tubules were less dilated, and the debris in them, although loosely disposed, occupied a much greater proportion of the lumen than in the paraffin sections. It is felt that the distortion brought about by the dehydration consequent upon the paraffin method makes this technique unsatisfactory for correctly assessing the changes that take place in these delicate structures in the anuric condition. 6. The great increase in the osmotic resistance of the red cells to saline, and to lyso-lecithin, was not related to any changes in the cell volumes, thicknesses, diameters or ratios, and the Price-Jones curve was within normal range. We feel that changes in the cells' environment, perhaps in the nature of circulating haemolysins, are more fundamental than physical changes in red cell structure that are considered by some to render them more susceptible to destruction.