Definition and Pathophysiology

If urine output is greater than 3 L/day and the urine is dilute (urine osmolality <250 mOsm/L), total solute excretion is relatively normal, and polyuria is due to excessive excretion of water. In general, diuresis is marked and urine osmolality (Uosm) is often less than 100 mOsm/L. Water diuresis is usually secondary to excess water intake (as in primary polydipsia) or inability of the renal tubules to reabsorb free water (as in central or nephrogenic diabetes insipidus). A good understanding of water homeostasis is critical for recognizing and managing water diuresis.

Normal plasma osmolality is 275 to 285 mOsm/L. To maintain this steady state, water intake must equal water excretion. The primary stimulus for water ingestion is thirst, mediated either by an increase in effective osmolality or a decrease in blood pressure (BP) or effective circulating volume. Under normal circumstances, water intake generally exceeds physiologic requirements.

Unlike water intake, water excretion is very tightly regulated by multiple factors. The most dominant regulating factor affecting water excretion is arginine vasopressin (AVP), a polypeptide synthesized in the hypothalamus and secreted by the posterior pituitary gland. Once released, AVP binds to vasopressin-2 (V2) receptors located on the basolateral membranes of renal epithelial cells lining the collecting ducts. Binding of AVP to V2 receptors initiates a sequence of cellular events, ultimately resulting in insertion of water channels into the luminal cell membrane. The presence of these water channels permits passive diffusion of water (hence its reabsorption) across the collecting duct. Any derangement in this process results in lack of or inadequate water reabsorption by the collecting duct, resulting in water diuresis. The major stimulus for AVP release is plasma hypertonicity. AVP release is also affected by other nonosmotic factors like effective circulating volume, hypoglycemia, and drugs. In summary, water diuresis occurs either because of excessive water intake sufficient enough to overwhelm the renal excretory capacity (primary polydipsia) or impairment of renal water reabsorption itself (central or nephrogenic diabetes insipidus). Impaired renal water reabsorptive capacity (leading to water diuresis) in turn can occur either as a result of failure of AVP release in response to normal physiologic stimuli (central or neurogenic diabetes insipidus) or failure of the kidney to respond to AVP (nephrogenic diabetes insipidus). In most patients, the degree of polyuria is primarily determined by the degree of AVP lack or resistance.

Primary Polydipsia

Primary polydipsia can be recognized clinically based on the history of the patient. Usually there is a history of psychiatric illness along with a history of excessive water intake. Many patients with chronic psychiatric illnesses have a moderate to marked increase in water intake (up to 40 L/day).^3,4 It is presumed that a central defect in thirst regulation plays an important role in the pathogenesis of primary polydipsia. In some cases, the osmotic threshold for thirst is reduced below the threshold for the release of AVP. The mechanism responsible for abnormal thirst regulation in this setting is unclear. There is evidence that these patients have other defects in central neurohumoral control as well.⁵ Hyponatremia, when present, also points to the diagnosis of primary polydipsia. The diagnosis of primary polydipsia is usually evident from low urine and plasma osmolalities in the face of polyuria. Hypothalamic diseases such as sarcoidosis, trauma, and certain drugs like phenothiazines can lead to primary polydipsia (Table 10-1). There is no proven specific therapy for psychogenic polydipsia. Free water restriction is the mainstay of therapy.

TABLE 10-1 Causes of Polyuria