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Disorders of Water Balance Endocrine Fellows Foundation June 15, 2004
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body fluid compartments
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neurohypophysis
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two major nuerohypophyseal peptides
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increased osmolality...
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higher AVP levels are necessary.....
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AVP receptor subtypes
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AVP receptor diagram 1
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antidiuresis is accomplished by shuttling of vesicular aquaporin-2 water channels into the apical membrane of collecting duct cells in response to AVP-mediated increases in intracellular cAMP levels
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three relationships determine urine volume....
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disorders of inappropriately increased AVP or AVP effect
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Hyponatremia - Incidence
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Hyponatremia can be caused by dilution....
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ECF Volume Status....
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a spot urine [Na+] <30 mEq/L generally identifies patients who respond to isotonic saline, and therefore are volume depleted, from those who do not, and therefore are more likely to have SIADH
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SIADH: essential criteria
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plasma AVP levels in patients with SIADH: 10-15% are below typical detection limits
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tumors pulmonary mediastinal extrathoracic
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requirements for producing hyponatremia
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neurological symptoms are roughly correlated with the level of hyponatremia, but with considerable individual variability across patients
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true loss of brain solute can reduce or eliminate brain edema despite severe hypoosmolality time dependent process
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brain volume regulation accounts for the differences in mortality rates between acute and chronic hyponatremia
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pontine and extrapontine myelinolysis: clinical manifestations
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central pontine myelinolysis white areas in the middle of the pons indicate massive demyelination of descending axons (corticobulbar and corticospinal tracts)
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safe correction of hyponatremia entails balancing the risks of the hyponatremia versus the risks of the correction. These, in turn, depend on the degree of brain volume regulation that has occurred
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limited controlled correction
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equal numbers of male and female patients become hyponatremic, but in some series a disproportionate percentage of brain damage occurred in females
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SIADH: chronic therapy
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Diagram 1
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WM: 63 y.o. female
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disorders of inappropriately decreased AVP or AVP effect
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neurogenic (central) DI
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MRI 1
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Diagram 2
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posterior pituitary "bright spot"
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Langerhans' - cell histiocytosis
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lymphocytic infundibuloneurohypophysitis
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etiology of DI in 79 pediatric patients
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MRI - 2
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nephrogenic (renal) DI
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mutations in the AVP V2 receptor gene associated with hereditary nephrogenic DI
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mutations in the aquaporin-2 gene associated with hereditary nephrogenic DI
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Not all polyuria is a result of defects in AVP secretion or AVP receptor activation!
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primary polydipsia
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plasma osmolality is usually normal in patients with all causes of polyuria
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water deprivation test
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plasma AVP levels can differentiate CDI from other types of polyuria, but only when plasma osmolality is >295 mOsm/kg
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diabetes insipidus: treatment
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AVP - D DAVP chart
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dDAVP vs. AVP
