PLASMA AND URINE OSMOLALITY

Determination of plasma and urine osmolality can be useful in the assessment of electrolyte and acid-base disorders. Comparison of plasma and urine osmolalities can determine the appropriateness and status of water regulation by the kidneys in settings of severe electrolyte disturbances, as might occur in diabetes insipidus or the syndrome of inappropriate antidiuretic hormone (SIADH) (see Chapters 45 and 50). The major osmotic substances in normal plasma are Ha, Cr, glucose, and urea thus expected plasma osmolality can be calculated from the following empirical equation  

The 9mOsmol/kg added to the above equation represents the contribution of other osmoticaUy active substances in plasma, such as K , Ca , and proteins, and 1.86 is two times the osmotic coefficient of Na, reflecting the contributions of both Na and CT. The reference interval for plasma osmolality is 275 to 300mOsmol/kg. Comparison of measured osmolality with calculated osmolality can help identify the presence of an osmolal gap, which can be important in determining the presence of exogenous osmotic substances. Comparison of calculated and measured osmolalities can also confirm or rule out suspected pseudohyponatremia caused by the previously discussed electrolyte exclusion effect. 

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Overnight water deprivation test (Box 50-9) If the ratio of urine to plasma osmolality is <1.5 at the end of the test, primary polydipsia is unlikeiy. Measure plasma and urine osmolalities and plasma ADH concentrations at the end of the test use these relationships to differentiate normal, nephrogenic, or hypothalamic diabetes insipidus, and psychogenic polydipsia. If urine osmoiahty is <400 mOsm/kg at the end of the test, give 5 U of aqueous vasopressin subcutaneously. If urine osmolality increases >10%, hypothalamic diabetes insipidus is probable if urine osmolality does not increase, nephrogenic diabetes insipidus is highly probable. 

Diagnostic Studies. A differential diagnosis of polyuric states can be made using measurements of plasma and urine osmolality and plasma AVP concentrations a recommended strategy is shown in Box 50-8. 

Procedure The test is started in the morning 2 hours after the patient has eaten a light breakfast. Plasma and urine osmolalities are measured. The patient is given water to drink (20mL/kg) over a 15- to 30-minnte period hghtly salted crackers may be given with the water if needed. The patient is kept in a recumbent position, and specimens are taken hourly for the next 4 hours for assessment of plasma and urine osmolality. Total urine output is measured. 

Measurements of osmotic pressure (osmometry) are most useful when a direct comparison is made between plasma and urine osmolality. In inappropriate ADH secretion, high urine osmolalities with low plasma osmolalities are found. In diabetes insipidus the opposite is found, i.e. low urine osmolalities with high plasma osmolalities. 

Whole blood and urine pH and Pco2 are measured quantitatively by an electrode blood-gas system and HCO3 concentrations are calculated. Plasma and urine Na+ and K+ concentrations are measured by flame photometry and CP concentrations by electrotitration. Plasma total protein concentrations and urine specific gravity are measured by refractometry, and hematocrits are determined by a microcapillary reader. Urine osmolalities are determined by freezing-point osmometry. Plasma creatinine concentrations are determined by the Jaffe method without deproteiniza-tion. 

The autonomous, sustained production of AVP in the absence of known stimuli for its release is called SIADH. In this syndrome, plasma AVP concentrations are inappropriately increased relative to a low plasma osmolality and to a normal or increased plasma volume. SIADH may be the result of one of several factors production of vasopressin by a malignancy (such as a small cell carcinoma of the lung), the presence of acute and chronic diseases of the central nervous system, pulmonary disorders, or a side effect of certain drug therapies. In addition, as many as 10% of patients undergoing pituitary surgery have a transient SIADH approximately 8 to 9 days after surgery (when the patient is at home), which responds to water restriction (2 to 3 days) and resolves without recurrence. In SIADH, a primary excess of AVP, coupled with unrestricted fluid intake, promotes increased reabsorption of free water by the kidney. The result is a decreased urine volume and an increased urine sodium concentration and urine osmolality. As a consequence of water retention, these patients become modestly volume expanded. The increase in intravascular volume causes hemodilution accompanied by dilutional hyponatremia and a low plasma osmolality. Volume expan-... 

Interpretation Plasma osmolality should decrease by >5 mOsm/kg, and urine osmolality should drop to <100 mOsm/kg, with 90% or more of the water load excreted in 4 hours. SIADH is characterized by excretion of <90% of the water load and by urine osmolality that remains at >100mOsm/kg. Plasma ADH may be measured at 90 or 120 minutes after the water loading to confirm the diagnosis. Subnormal responses are seen with glucocorticoid deficiency, hypothyroidism, and renal diseases,... 

While some clinical and laboratory findings assist in the general diagnosis of ARF, others are used to differentiate between prerenal, intrinsic, and postrenal ARF. For example, patients with prerenal ARF typically demonstrate enhanced sodium reabsorption, which is reflected by a low urine sodium concentration and a low fractional excretion of sodium. Urine is typically more concentrated with prerenal ARF and there is a higher urine osmolality and urine plasma creatinine ratio compared to intrinsic and postrenal ARF. 

Statistical Methods. Means of treatment groups for plasma retention of BSP, plasma osmolality, total plasma protein concentration and urine flow rates were compared by students t test for independent sample means (17). Plasma enzyme activity data were converted to a quantal form and analyzed by the Fischer Exact Probability Test (18). Values greater than 2 standard deviations (P < 0.05) from the control value were chosen to indicate a positive response in treated fish. 

A 17-year-old who took olanzapine 75 mg and praze-pam 7.5 mg in a suicide attempt developed polyuria (5400 ml/24 hours), reduced urine osmolality (166 mos-mol/kg H20), normal plasma osmolality, and an increasing serum sodium concentration, consistent with a diagnosis of diabetes insipidus (259). 

An 18-year-old woman developed impaired consciousness, psychomotor shaking, hallucinations, tics, and delirium. Her serum sodium concentration was low at 120 mmol/1 with a plasma osmolality of 242 mosm/kg and a urine osmolality of 562 mosm/kg, suggesting SIADH. Most other blood tests were within the reference ranges, except for a raised creatine kinase. Urine toxic screen was positive for amphetamines. Treatment with hypertonic saline brought about resolution of symptoms. The patient recalled taking three ecstasy tablets over 6 hours. 

A variety of tumours, e.g. oat-cell limg cancer, can make vasopressin, and of course they are not subject to normal homeostatic mechanisms. SIADH also occurs in some CNS and respiratory disorders (infection). Dilutional hyponatraemia follows, i.e. low plasma sodium with an inappropriately low plasma osmolality and high urine osmolality. When the plasma sodium approaches 120 mmol/I treatment should be with fluid restriction (< 500 ml/day). Treatment is primarily of the imderlying disorder accompanied by fluid restriction. Chemotherapy to the causative tumour or infection is likely to be the most effective treatment. Demeclocycline, which inhibits the renal action of vasopressin, is useful Infusion of isotonic or hypertonic saline must be reserved for extreme emergencies, associated with stupor, and undertaken with great caution. Rapid correction of hyponatraemia must be avoided because of the risk of central pontine myelinolysis the rate of correction must not exceed 12 mmol/1 per 24 h. 

In general, the sediment in the urine is normal. Proteinuria or erythrocyturia are not characteristic of hepatorenal syndrome. The excretion of sodium in the urine is lower than 10 mmol/day, with a fractional excretion of sodium of < 1%. For this reason, there is likewise increased renal retention of water. The urine osmolality is greater than the plasma osmolality, which results in a quotient of >1.3. With increasing severity of hepatorenal syndrome and transition of the penultimate phase, the urine becomes iso-osmotic with an osmolality quotient of 1 or < 1. (19, 43,52,53, 60) (s. tab. 17.4)... 

In hypoosmotic hyponatremia with a normal volume status, the most common etiologies are the syndrome of inappropriate ADH (SIADH), primary polydipsia, hypothyroidism, and adrenal insufficiency (see Figure 46-2). SIADH is usually a result of ectopic or otherwise inappropriate ADH production arising from a variety of conditions (see Chapters 45 and 50) and results in excessive H2O retention. SIADH is often diagnosed when a urine osmolality that is greater than plasma osmolality (usually by more than >i00 mOsmol/kg) is observed in the setting of hyponatremia, but only when renal, adrenal, and thyroid functions are normal. Hypothyroidism impairs free H2O excretion, whereas in adrenal insufficiency, Na" is lost in preference to IC reabsorption. Finally, euvolemic hyponatremia can be... 

FIGURE 49-5. Water deprivation test The change in plasma osmolality is plotted against the change in urine osmolality following water deprivation and subcutaneous administration of 5 meg of desmopressin acetate. DI, diabetes insipidus Posm, plasma osmolality Uosm, urine osmolality. (Adapted from Rose et al. )... 

In rats treated with lithium, dDAVP, a specific V2 agonist, produced an increase in urine osmolality associated with increased apical plasma membrane AQP2 labeling. The action of dDAVP was likely due, at least in part, to its ability to overcome the block of adenylate cyclase caused by lithium. This may cause relocation of AQP2 to the apical part of the cell, and presumably induction of water channel insertion into the plasma membrane may be restored [55,58]. The stimulatory effect of dDVAP in the presence of lithium, to... 

Osmolality is dependent on the number of particles present in solution it is measured by freezing point depression or vapor pressure and results are expressed as millios-moles per kilogram of body water (Sweeney and Beauchat 1993). When urine and plasma osmolality measurements are available, the plasma-to-urine ratio can be used as a broad indication of the glomerular hltrate to urine ratio. Handheld refractometers... 

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