Osmolality of urine

The osmolality of urine can differ markedly from that of plasma because of active concentrative processes in the renal tubules. The membranes of renal collecting ducts show varying degrees of water permeability and permit removal of certain solutes without simultaneous uptake of water. 

The simplest measure of the ability of the kidney to conserve water is provided by osmolality of urine excreted by a water-deprived subject. The osmolality of plasma changes relatively little and averages close to 300 mOsm analysis of the osmolar concentration of urine thus leads directly to the (U/P) osmol ratio. Simple and convenient osometers are available for such determinations. Human urine may range from osmolalities below 100 mOsm to a maximum of perhaps 1800, that is, to a urine sixfold more concentrated than plasma. The rat, in contrast, can readily concentrate its urine nine- to tenfold. 

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. 

Fluid restriction is generally unnecessary as long as sodium intake is controlled. The thirst mechanism remains intact in CKD to maintain total body water and plasma osmolality near normal levels. Fluid intake should be maintained at the rate of urine output to replace urine losses, usually fixed at approximately 2 L/day as urine concentrating ability is lost. Significant increases in free water intake orally or intravenously can precipitate volume overload and hyponatremia. Patients with stage 5 CKD require renal replacement therapy to maintain normal volume status. Fluid intake is often limited in patients receiving hemodialysis to prevent fluid overload between dialysis sessions. 

TBW depletion (often referred to as dehydration ) is typically a more gradual, chronic problem compared to ECF depletion. Because TBW depletion represents a loss of hypotonic fluid (proportionally more water is lost than sodium) from all body compartments, a primary disturbance of osmolality is usually seen. The signs and symptoms of TBW depletion include CNS disturbances (mental status changes, seizures, and coma), excessive thirst, dry mucous membranes, decreased skin turgor, elevated serum sodium, increased plasma osmolality, concentrated urine, and acute weight loss. Common causes of TBW depletion include insufficient oral intake, excessive insensible losses, diabetes insipidus, excessive osmotic diuresis, and impaired renal concentrating mechanisms. Long-term care residents are frequently admitted to the acute care hospital with TBW depletion secondary to lack of adequate oral intake, often with concurrent excessive insensible losses. 

Concentrating ability of the kidney (measurement of urine osmolality assessed following withdrawal of food and water for 24 h free water clearance)... 

The major characteristics of the renal response to mannitol diuresis include a fall in urine osmolality and a decrease in the osmolality of the interstitial fluid of the renal medulla. The quantity of urine formation and Na excretion is generally proportional to the amount of mannitol excreted. Although there is a significant inhibition of proximal water reabsorption, the effects of mannitol on proximal Na+ reabsorption are not marked. 

Hyponatmemia is common with the thiazides and to a lesser extent with the loop diuretics. It occurs when the osmolality of the urine persistently exceeds that of the fluid intake and is associated with the inability of the kidney to produce a dilute urine. It is not usually severe. The origin is multifactorial and involves unrestricted fluid intake and increased ADH activity due to volume depletion. Co-administration of dipsogenic drugs, such as the tricyclic antidepressants, or those with ADH-like effects, such as chlorpropamide, can exacerbate the problem. There are rare occasions when hyponatraemia (Nan- concentration less than 100 mmol-L-l) can be of sufficient severity to be life threatening. 

Urea concentration in the medulla plays an important role maintaining the high osmolarity of the medulla and in the concentration of urine. ADH secretion is regulated by serum osmolality and by volume status. A new class of drugs, the vaptans (see under Agents That Alter Water Excretion), are ADH antagonists. 

A 76-year-old woman taking lisinopril 20 mg/day and metoprolol for hypertension developed headaches, nausea, and a tingling sensation in her arms. Her serum sodium was 109 mmol/1, with a serum osmolality of 225 mosm/kg, urine osmolality of 414 mosm/kg, and urine sodium of 122 mmol/1. She had taken diclofenac 75 mg/day for arthritic pain for 6 years and naproxen for about 1 month. Propoxyphene napsylate and paracetamol had then been substituted and zolpidem had been started. A diagnosis of SIADH was postulated and thyroid and adrenal causes were excluded. Lisinopril was withdrawn and fluid was restricted to 100 ml/day. The serum sodium gradually corrected to 143 mmol/1. 

Glucose begins to spill into the urine as the proteins responsible for reclaiming it from urine reach maximum capacity. As glucose is excreted in the urine, it takes a great deal of body water with it, resulting in dehydration. Dehydration further concentrates the blood and worsens the increased osmolality of the blood. Severe dehydration forces water out of cells and into the bloodstream to keep vital organs perfused. This shift of intracellular water into the bloodstream occurs at a cost, as the cells themselves need the water to complete chemical reactions that allow the cells to function. 

A healthy 19-year-old woman complained of nausea and vomited 8 hours after taking unknown quantities of MDMA and beer 3 hours later, she suddenly clenched her jaw, had tonic contractions of all four limbs, and collapsed. She was obtunded, with occasional moaning and non-purposeful movements of the limbs. Head CT scan showed mild cerebral edema. Her serum electrolytes, including a sodium of 115 mmol/1 and a corresponding urine osmolality of 522 mosm/kg, suggested SIADH. Despite treatment, the serum sodium concentration 10 hours later was 116 mmol/1, but 18 hours after treatment, it rose to 125 mmol/1. She became progressively more responsive, with normalization of her sodium concentration, and after 48 hours was awake and alert, with a serum sodium concentration of 136 mmol/1. 

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. 

Water is present in a free (non-osmotically bound) state and as a chemically bound hydrate solid structure. The clearance of free water is controlled by vasopressin it is calculated from the volume of urine/minute minus the osmolal clearance. A normal daily fluid intake of 1,700-2,200 ml (25-30 ml/kg BW) in addition to some 300 ml oxidation water is balanced by a fluid discharge of approximately 1,500 ml as urine, about 100 ml in stools, roughly 600 ml as perspiration and some 400 ml as expired air. (s. fig. 16.1)... 

Best results with Azone (clinical effect in vivo reduction of urine volume and increase in urine osmolality)... 

Urine Urinalysis with microscopic examinination of urine sediment Albumin Retinol binding protein N-acetyl-p-D-glucosaminidase Alanine aminopeptidase Osmolality Creatinine Glomerulus Proximal tubule Proximal tubule Proximal tubule Distal tubule Control for urine concentration... 

Figure 3. Maximal urine osmolality after fluid deprivation and vasopressin administration during (closed circles) and before (open circles) amiloride administration. The shaded area shows the range of urine osmolality in normal subjects tested after fluid deprivation and vasopressin administration in our laboratory. Li denotes lithium and Li + A lithium plus amiloride (reproduced from Batlle et al [26]).

The urinary osmolality of normal individuals may vary widely, depending on the state of hydration. After excessive intake of fluids, for example, the osmotic concentration may fall as low as 50 mOsm/kg/H20, whereas in individuals with severely restricted fluid intake, concentrations of up to 1400mOsm/kg/H2O can be observed. In individuals on an average fluid intake, values of 300 to 900 mOsm/kg/H20 are typically seen. If a random urine specimen of a patient has an osmolality of >600 mOsm/kg/H20 (or >850mOsm/kg/ H2O after 12 hours of fluid restriction), it can generally be assumed that the renal concentrating ability is normal. 

Hypernatremia in the setting of decreased ECF is caused by the renal or extrarenal loss of hypoosmotic fluid leading to dehydration. Thus once hypovolemia is established, measurement of urine Na" " and osmolality is used to determine the source of fluid loss. Patients who have large extrarenal losses have a concentrated urine (>800 mOsmol/L) with low urine Na (<20 mmol/L), reflecting the proper renal response to conserve Na and water as a means to restore ECF volume. Extrarenal causes include diarrhea, skin (burns or excessive sweating), or respiratory losses coupled with failure to replace the lost water. When gastrointestinal loss is excluded, and the patient has normal mental status and access to H2O, a hypothalamic disorder (tumor or granuloma) should be suspected, because the normal thirst response should always replace insensible water losses. 

Document polyuria (urine volume >2.5L/day) and exclude glycosuria. If desired, creatinine excretion can be measured as an estimate of completeness of urine collections snbstances that inflnence ADH secretion should be avoided (e.g., nicotine, alcohol, and caffeine). If plasma osmolality is >295 mOsm/kg or if serum sodium concentration >145mmol/L, primary polydipsia is unlikely proceed with the overnight water deprivation test (Box 50-9) or the hypertonic saline infusion test (Box 50-10). 

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. 

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. 

In persons with normal kidney function, sodium balance is maintained at a sodium intake of 120 to 150 mEq/day. The fractional excretion of sodium (FENa) is approximately 1% to 3%. Water balance is also maintained, with a normal range of urinary osmolality of 50 to 1200 mOsm/L. In patients with severe CKD (Stages 4 and 5), sodium balance is achieved, but results in a volume-expanded state. FENa may increase to as much as 10% to 20%, possibly due to increased concentrations of atrial natriuretic peptide. An osmotic diuresis occurs with an increase in FENa leading to obligatory water losses and impairment in the kidney s ability to dilute or concentrate urine (urinary osmolality is often fixed at that of plasma or approximately 300 mOsm/L). Nocturia is present relatively early in the course of CKD (Stage 3) secondary to the defect in urinary concentrating ability. Total renal sodium excretion decreases despite an increase in sodium excretion by remaining nephrons. Volume overload with pulmonary edema can result, but the most common manifestation of increased intravascular volume is systemic hypertension. ... 

Patients with hypovolemic hypotonic hyponatremia, on the other hand, should be treated with normal saline because the concentration of osmotically effective urine cations is invariably less than that of isotonic saline. In contrast to patients with SIADH, sodium is avidly reabsorbed throughout the nephron when the effective circulating blood volume is decreased. Thus the urine osmolality is primarily comprised of urea, and the concentration of urine sodium is often less than 20 ruEq/L. 

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. )... 

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