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Why should there be Metabolic acidosis in multiple myeloma?
Thanks for the question.
It seems to be due to a toxic effect on tubular cells that reabsorb light chains, are initially processed in lysosomes, some light chains are indestructible, crystallize and damage the tubules thus causing renal failure, loss of bicarbonate and thus acidosis.
The following paragraph from Upt0D4te ''
RENAL TUBULAR DYSFUNCTION — In some patients, the toxic effect of filtered light chains is limited to tubular dysfunction, with the glomerular filtration rate being relatively well maintained. The proximal tubules are most prominently affected, due to the reabsorption of filtered light chains and their subsequent accumulation in the proximal tubular cells . The light chains that produce this lesion appear to have a unique biochemical characteristic in that part of the variable domain is resistant to degradation by proteases in lysosomes in the tubular cells . Accumulation of the variable domain fragments, with subsequent intracellular crystal formation, is presumably responsible for the impairment in tubular function .
The clinical manifestations of tubular dysfunction include signs of the Fanconi syndrome such as proximal renal tubular acidosis and phosphate wasting; the latter can lead to hypophosphatemia and osteomalacia [32,33]. Proximal dysfunction can also exacerbate myeloma kidney by decreasing light chain reabsorption, thereby increasing light chain delivery to and promoting precipitation in the distal nephron. An important laboratory finding is the presence of hypouricemia (in the absence of allopurinol therapy) as well as aminoaciduria"
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