AJP - Endocrinology and Metabolism, Vol 259, Issue 5 E723-E728, Copyright © 1990 by American Physiological Society
Osmoregulation of vasopressin in diabetic ketoacidosis
J. A. Durr, W. H. Hoffman, J. Hensen, A. H. Sklar, T. el Gammal and C. M. Steinhart
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.
Osmoregulation of arginine vasopressin (AVP) is altered in diabetic
ketoacidosis (DKA). With hyperglycemia, the AVP-plasma sodium (PNa) curve
is displaced to the left, whereas the AVP-osmolality (Posm) curve is
displaced to the right. The shift in the Na curve is explained by either
resetting of the Na set point or by glucose acting as a nonpermeable
solute, substituting for Na. Conversely, putative unmeasured solutes that,
like urea, fail to affect AVP have been postulated to account for the right
shift in the AVP-Posm curve. Therefore the respective roles of Posm = sigma
[Xi] and plasma tonicity (Pton = sigma [sigmaiXi]), i.e., the sum of
concentrations of all solutes [Xi] corrected (Pton) or not (Posm) for their
relative cell permeability (sigma i), were studied in DKA. Indeed, Posm =
sigma [Xi] exceeds Pton = sigma [sigma iXi] in DKA, since sigma i less than
1 for glucose. Potential determinants of AVP release (Posm, Pton, and PNa)
were monitored in 7 patients with DKA. Conventional correlation analysis
and two-dimensional (2D) graphs reproduced the paradox of an opposite shift
in PNa and Posm set points for AVP release. However, by using the concept
of tonicity instead of osmolality, 3D plots instead of 2D graphs, and
multiple regressions instead of correlations, the AVP-PNa and AVP-Pton
curves did not appear displaced. The concept of tonicity resolved the
paradox of both osmolality and Na thresholds reset in opposite directions.
Indeed, in states where a solute like glucose (with sigma less than 1)
contributes substantially to plasma osmolality, Posm measured in vitro by
the osmometer greatly exceeds Pton perceived in vivo by the osmoreceptor.
