Health Questions and Answers

REGULATION OF SODIUM, WATER, AND VOLUME STATUS

How do you estimate a patient’s serum osmolality?
A close estimate can be derived from measurements of the serum sodium (Na+), glucose, and blood urea nitrogen (BUN), using the following equation:

What percentage of the adult human body consists of water? What percentage of the water content is intracellular versus extracellular?
Approximately 60% of the adult man and 50% of the adult woman are water. About two thirds of this volume is intracellular, and one third is extracellular. About 20% of the extracellular fluid volume is plasma water.

What are the sources and daily amounts of water gain and loss?
The average adult male gains and loses 2600 mL of water each day. The gains occur from direct fluid ingestion (1400 mL/day), from the fluid content of ingested food (850 mL/day), and as a product of water produced by oxidation reactions (350 mL/day). Water losses occur through urine (1500 mL/day), perspiration (500 mL/day), respiration (400 mL/day), and feces (200 mL/day).

List the factors necessary to allow the kidney to excrete free water.

  1. A filtrate must be formed to allow renal excretion of free water.
  2. Glomerular filtrate must escape reabsorption in the proximal tubule to reach the diluting segment (ascending loop of Henle), where free water is created.
  3. An adequately functioning diluting segment must be present.
  4. The free water formed by the diluting segment must leave the nephron without being reabsorbed by the collecting tubule. This nephron segment is intrinsically impermeable to water but is made permeable by antidiuretic hormone (ADH).

Summarize the relationship between glomerular filtration rate (GFR) and excretion of free water.
The lower the GFR, the lower the kidney’s ability to respond rapidly to a free-water challenge with excretion of free water.

What pathologic states can affect fluid reabsorption in the proximal tubule?
Pathologic states involving vigorous fluid reabsorption in the proximal tubule are associated with a compromised ability to excrete free water. Examples include true volume depletion and states of decreased effective arterial blood volume, such as congestive heart failure, cirrhosis, and nephrotic syndrome.

What pathologic states can affect functioning of the diluting segment?
Intrinsic disorders of function of the diluting segment are unusual. Endogenous prostaglandin E2 and loop diuretics inhibit NaCl transport in this segment and can thereby limit formation of free water.

Explain the meaning of serum sodium concentration with respect to sodium balance and water balance.
Serum Na+ concentration [Na+], measured in mEq/L, reflects the concentration of this cation in extracellular fluid (ECF). Because its units are measured as mass per unit volume, [Na+] indicates the relationship between Na+ and water in the body. It is not indicative of total body Na+ content but is more an indication of the water status (hydration) of the body. [Na+] may be low, normal, or increased with any given perturbation of total body Na+ content. Alterations of the [Na+] reflect alterations in free-water balance. Therefore, a true low [Na+] indicates a free-water excess compared to Na+ content, and a high [Na+] indicates a relative free-water deficit.

What is meant by a state of decreased effective arterial blood volume?
The extracellular space is dynamic, with an ongoing balance between its capacity and its actual volume. Both parameters are biologically monitored and normally coordinated to maintain optimal tissue perfusion. A state of decreased effective arterial blood volume occurs when a large capacity is combined with a smaller volume, as seen most commonly with congestive heart failure, cirrhosis, and nephrotic syndrome. Isotonic fluid losses, such as hemorrhage, cause a decrease in ECF volume with no change in [Na+]. If, however, these losses are replaced with hypotonic fluids, dilutional hyponatremia results.

Why does Na+ have an effective distribution in total body water despite being confined largely to the extracellular space?
Na+ is the major determinant of serum osmolality, and changes in its concentration lead to water shifts between the extracellular and intracellular compartments. This osmotic shift of water gives Na+ an effective distribution greater than its chemical distribution and equivalent to that for total body water.

What is hyperosmolar hyponatremia?
Hyperosmolar hyponatremia is defined as serum osmolarity > 295 mOsm/kg H2O. It usually results from administration of hypertonic solutions of dextrose or mannitol.

What is hyposmolar hyponatremia?
Hyposmolar hyponatremia is defined as serum osmolality < 280 mOsm/kg H2O). It can be associated with low, normal, or increased volume status and is seen with diuretic administration, salt-losing renal conditions, syndrome of inappropriate ADH secretion (SIADH), chronic renal failure, and a wide range of other causes.

How can patients with hyposmolar hyponatremia be categorized according to history and physical findings?
Patients with hyposmolar hyponatremia can be categorized as hypovolemic, hypervolemic, or euvolemic according to volume status as estimated from the physical exam and history.

What findings suggest a hypovolemic state?
Hypovolemia is supported by a history of volume loss or decreased intake and orthostatic blood pressure changes on examination.

How is the hypovolemia treated?
The lost volume must be replaced to turn off the factors that limit the kidney’s ability to excrete free water.

How do you recognize the hypervolemic patient?
Hypervolemia is supported by a history of a condition with decreased effective arterial blood volume and an examination showing edema.

Describe the treatment of the hypervolemia.
Therapeutic attention must be directed to the underlying disorder. If the hyponatremia is mild and asymptomatic, free-water restriction, in addition to specific treatment of the underlying disorder, is the suggested initial therapeutic approach. If the hyponatremia is severe and symptomatic, more aggressive treatment with hypertonic saline and furosemide may be required.

Summarize the approach to euvolemic hyposmolar hyponatremia.
In patients with hyposmolar hyponatremia and apparently normal volume status or euvolemia, a wide variety of pathologic processes must be considered in the diagnostic evaluation, including SIADH and drugs that can limit free-water excretion (e.g., chlorpropamide).

Define pseudohyponatremia.
Pseudohyponatremia occurs when a quantitative serum Na+ measurement is performed on a given volume of plasma that contains a greater-than-normal amount of water-excluding particles, such as lipid or protein. In this setting, plasma water (which contains the Na+) composes a smaller fraction of the plasma volume, leading to a factitiously low serum Na+ concentration (when expressed in mEq/L). The Na+ concentration in plasma water is normal, and therefore patients are asymptomatic. Attention should be directed to hyperlipidemia or hyperproteinemia.

How is spurious hyponatremia different from pseudohyponatremia?
Spurious hyponatremia results from hyperosmolality of the serum (i.e., from hyperglycemia), resulting in movement of intracellular water to the extracellular space and subsequent dilution of the Na+ in the ECF. These patients are not symptomatic from hyposmolality (unlike patients with true hyponatremia). If they are symptomatic at all, it is due to their hyperosmolar state. Attention should be directed to correcting the hyperosmolar state. It is important to distinguish these two categories of hyponatremia from true hyponatremia associated with hyposmolality because the diagnostic work-up and therapeutic management are different.

How do you correct the serum Na+ for a given level of hyperglycemia?
Hyperglycemia, one of the causes of spurious hyponatremia, causes a decrease in the measured serum Na+ concentration. For each increase in serum glucose of 100 mg/dL up to 600 mg/dL (an increase of 500, or 5 ×100 mg/dL), the serum Na+ decreases by 8.0 mEq/L (5 × 1.6 mEq/L).

Define essential hyponatremia.
Essential hyponatremia, or “sick cell syndrome,” denotes hyponatremia in the absence of a water diuresis defect. One hypothesis is that the osmoreceptor cells in the hypothalamus are reset so that they maintain a lower plasma osmolality. This is seen in several conditions, such as congestive heart failure, cirrhosis, and pulmonary tuberculosis, and is diagnosed by demonstrating normal urinary Na+ concentration and dilution in the face of hyponatremia. Generally, this entity does not require treatment.

What are the signs and symptoms of hyponatremia?
The manifestations are mainly attributable to CNS edema, which is usually not seen until the serum Na+ falls to 120 mEq/L or less. Symptoms range from mild lethargy to seizure, coma, and death. The signs and symptoms of hyponatremia are more a function of the rapidity of the drop in serum Na+ than the absolute level. In patients with chronic hyponatremia, there has been time for solute equilibration, resulting in less CNS edema and less severe manifestations. In acute hyponatremia, there is no time for equilibration, and so smaller changes in serum Na+ are accompanied by larger degrees of CNS edema and more severe manifestations.

Why is hyponatremia often seen after transurethral resection of the prostate (TURP)?
Often during the TURP procedure, large volumes of solutions containing mannitol, glycerol, or sorbitol are used to irrigate the prostate. A variable fraction of these fluids is absorbed into the systemic circulation, producing hyponatremia.

How do you manage hyponatremia in edematous states?
Treatment depends on the underlying etiology, any symptoms, and the rapidity of the drop in serum Na+. In general, patients with edematous states such as the nephrotic syndrome, who have ECF expansion, have some degree of hyponatremia if they are not water-restricted. Generally, this condition is asymptomatic and requires no treatment. Treatment is required only if the hyponatremia is severe (< 125 mEq/L), and especially if there are symptoms such as lethargy, confusion, stupor, and coma. A 41-year-old black man is hospitalized with acute bacterial meningitis. His chemistry profile shows a BUN and creatinine of 11 and 1.2 mg/dL, respectively, but his serum Na+ is 127 mEq/L.

What is the likely cause of his hyponatremia?
Hyponatremia in the setting of bacterial meningitis (or any pathologic CNS process) is usually due to SIADH. SIADH is a form of hyponatremia involving sustained or spiking levels of ADH that are inappropriate for the osmotic or volume stimuli that normally affect ADH secretion.

List the essential points in the diagnosis of SIADH.

  1. Presence of hypotonic hyponatremia Inappropriate antidiuresis (urine osmolality higher than expected for the degree of hyponatremia)
  2. Significant Na+ excretion when the patient is normovolemic
  3. Normal renal, thyroid, and adrenal function
  4. Absence of other causes of hyponatremia, volume depletion, or edema


What is cerebral salt-wasting?
Due to impaired renal water excretion, this condition is associated with hyposmolar hyponatremia in patients with cerebral trauma or disease. It mimics SIADH in all aspects including hypouricemia except that in this syndrome patients are volume-depleted, while in SIADH, patients are euvolemic. The high urinary Na+ despite hypovolemia reflects renal salt-wasting. The etiology of this salt-wasting is unknown, although increased secretion of cerebral natriuretic factors is one likely explanation. A circulating factor that impairs renal tubular Na+ reabsorption is another likely possibility.

What are the manifestations of hypernatremia?
The manifestations of hypernatremia are basically those of hyperosmolality and are similar to the symptoms manifested by other causes of hyperosmolality, such as hyperglycemia. These are produced mainly by fluid shifts from the CNS and increased CNS osmolality, resulting in “shrinking” of the brain. The symptoms range from lethargy to seizures, coma, and death. The severity of the symptoms depends on the severity of the hyperosmolality and the speed with which it develops.

What are some common causes of hypernatremia?
Diabetes insipidus, severe dehydration due to extrarenal fluid losses (e.g., burns, excessive sweating), and hypothalamic disorders (e.g., tumors, granulomas, cerebrovascular accidents) leading to defective thirst and vasopressin regulation.

How do you correct hypernatremia?
Once the free-water deficit is calculated, hypernatremia is usually corrected by replacement of the water. In mild cases, this can be accomplished by simply having the patient drink or, if IV fluids are used, dextrose in water can be given. If salt-containing fluids are deemed necessary, the equivalent free-water volume must be given. For example, if half-normal saline is used (1 L of which contains 500 mL of normal saline and 500 mL of free water), then twice the amount of the estimated free-water deficit is needed to correct the free-water deficit. This volume deficit should be replaced slowly. The first half is given over 24 hours. If the patient is hemodynamically unstable, with signs of severe ECF volume depletion, therapy with 0.9% normal saline is warranted before dextrose infusion is started.
References
BIBLIOGRAPHY

  1. Brenner RM (ed): Brenner & Rector’s The Kidney, 7th ed. Philadelphia, W.B. Saunders, 2004.
  2. Goldman L, Ausiello D (eds): Cecil Textbook of Medicine, 22nd ed. Philadelphia, W.B. Saunders, 2004.
  3. Rose BD, Post T (eds): Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed. New York, McGraw-Hill, 2001.
  4. Schrier RW (ed): Renal and Electrolyte Disorders, 6th ed. Philadelphia, Lippincott Williams & Wilkins, 2003.
  5. Al-Mufti H, Arieff AI: Cerebral salt wasting syndrome: Combined cerebral and distal tubular lesion. Am J Med 77:740, 1984.

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