Interpreting and Correlating Abnormal Laboratory Values : Electrolyte Abnormalities

Electrolyte Abnormalities

Hyponatremia

The four most common causes of hyponatremia are given in Table 1 (See below), together with a fifth, rare, cause, Bartter's syndrome. A sixth, metabolic cause, diabetes mellitus, is also presented in this table. In all forms of hyponatremia, the chloride ion concentration is also generally low since chloride is the chief counter-ion for sodium.

Table 1. Common Causes of Hyponatremia and Electrolyte Patterns in Serum and Urine with Normal Renal Function^[*]

Cause	Serum Na	Urine Na (UNa)	Urine osmolality	Serum K	24-Hour UNa
1. Overhydration	Low	Low	Low	Normal or low	Low
2. Diuretics	Low	Low	Low	Low	High
3. SIADH**	Low	High	High	Normal or low	High
4. Adrenal failure	Low	Mildly elevated	Normal	High	High
5. Bartter's syndrome	Low	Low	Low	Low	High
6. Diabetic hyperosmolarity***	Low	Normal	Normal	High	Normal

*	All Na and K values are concentrations except for 24-hour UNa, which is the total number of milliequivalents of Na excreted in 24 hours in the urine.
**	Secretion of inappropriate levels of antidiuretic hormone.
***	In this condition, serum glucose is markedly elevated.

Basic Principle

All confirmed serum sodium abnormalities must be followed up with urinalysis on the patient who should be fluid restricted. This urinalysis should include the urine sodium and urine osmolality. For conditions 1 and 2 in Table 1 , the serum sodium tends to correct over a 24-hour period when the patient is fluid restricted.

Overhydration

In this condition, the most common cause of which is the consumption of large amounts of water or hypotonic fluids due to such causes as psychogenic polydipsia, serum sodium is reduced below 135 mEq/L. Since the consumed water is excreted by the kidneys, the urine is also dilute in this ion. In fact, the osmolality of urine will be low, i.e., < 300 mOsm. Often accompanying hyponatremia in overhydration are low values of the hematocrit and low values of BUN, discussed subsequently. This triad of findings strongly suggests overhydration as the cause. Urinalysis in the fluid-restricted patient will reveal urinary sodiums of < 25 mEq/L and low osmolalities. The potassium may also be low although it often remains within the reference range. Since mainly water is excreted in urine in this condition, the total 24-hour sodium excretion will be low (cause no. 1 in Table 1 ).

Use and/or Abuse of Diuretics.

Loop diuretics block the chloride pump in the loop of Henle, thereby blocking the formation of the ion gradients via the countercurrent multiplier, necessary for water conservation. Thus water is lost. Also, because sodium is no longer retained because it follows chloride in the loop, it also is depleted from serum. The 24-hour sodium excretion is high, unlike in over-hydration (entry 2 in Table 1). The pattern resembles overhydration (dilute serum and urine) except that loop diuretics cause severe potassium depletion unless the diuretic is combined with a potassium-sparing diuretic like triamterene. Combined hyponatremia and hypokalemia with a high urinary sodium and potassium 24-hour excretion point to diuretic use. Of course, a history will generally also reveal use of diuretics.

Syndrome of Inappropriate ADH (SIADH) Secretion

(entry 3, Table 1 ). In this condition, secondary to head trauma, seizures, other CNS diseases, and neoplastic conditions especially lung, breast and ovarian cancers, that secrete ADH-like hormones, the serum sodium is depressed due to the excess retention of water in the collecting ducts. This results in depletion of water in the renal tubules, thereby concentrating the urine. Therefore, while the serum is dilute in sodium (hypotonic), the urine is concentrated to levels > 40 mEq/L, and the urine osmolality exceeds 300 mOsm while the serum osmolality < 280 mOsm. This pattern clearly is diagnostic of SIADH.

Aldosterone Deficit

(entry 4, Table 1 ). This condition is secondary to Addison's disease and AIDS-related hypoadrenalism. Without aldosterone, the Na⁺–K⁺ and Na⁺–H⁺ exchange in the distal convoluted tubules and collecting ducts does not occur. Therefore, serum sodium concentration is reduced while serum potassium concentration increases, and there is a mild metabolic acidosis. Urinary sodium increases but not to the high levels seen in SIADH, and the osmolality of urine is also not so elevated as in SIADH.

Fig. Two patients with neonatal Bartter's syndrome described by Landau et al. Both patients have the typical facial appearance with prominent forehead, triangular face, drooping mouth, and large eyes and pinnae

Bartter's Syndrome

(entry 5, Table 1 ). This condition resembles diuretic use except that the hyponatremia is not corrected with fluid restriction. The cause of this rare condition is unknown, but sodium chloride gradients cannot form in the loop of Henle. This results in retention of chloride ion that is not available for the countercurrent mechanism. Thus the ion gradients that normally form in the loop of Henle cannot exist. In this condition, there is a persistent hyponatremia, hypokalemia and a high 24-hour sodium and potassium excretion.

Diabetic Hyperosmolar State.

In patients with diabetes mellitus, if they are in a hyperosmolar state, i.e., where the serum glucose is markedly elevated, say around 700 mg/dL, the hyperosmolality of serum causes efflux of cellular water, with a consequent osmotic dilution of serum sodium. Roughly, for each 100 mg/dL increase in serum glucose, there is a 1.6 mEq/L decrease in the serum Na⁺ concentration. Since transport of glucose into cells is accompanied by concurrent transport of potassium into cells, low insulin levels also cause high serum potassium. So, the net effect of diabetic hyperosmolar states is a low serum sodium and a high serum potassium. This resembles hypoaldosteronism (cause 4 in Table 1 ), but the presence of abnormally high glucose levels signals the possibility of diabetes mellitus as the cause.

Pseudohyponatremia

This condition is usually caused by the presence of excess lipids in serum. No sodium ions are dissolved in lipids, which can take up a considerable volume of serum. If the absolute amount of sodium in a given volume of serum is determined, as is performed when using such methods of sodium determination as flame photometry, this value is divided by the sample volume to get the concentration. But part of this volume is lipid that has no sodium. So a falsely low value of sodium can be obtained. This artifact is eliminated by the use of ion-selective electrodes that directly determine the concentration of sodium and do not depend upon knowledge of the volume of serum.

Hypernatremia

Table 2 summarizes the three basic causes of hypernatremia. Note that each cause is the counterpart of a cause for hyponatremia. These causes are summarized as follows.

Table 2 : Common Causes of Hypernatremia and Electrolyte Patterns in Serum and Urine with Normal Renal Function^[*]

Cause	Serum Na	Urine Na (UNa)	Urine osmolality	Serum K	24-Hour UNa
1. Dehydration	High	High	High	Normal	Varies
2. Diabetes insipidus	High	Low	Low	Normal	Low
3. Cushing's disease or syndrome	High	Low	Normal	Low	Low

*	All Na and K values are concentrations except for 24-hour UNa, which is the total number of milliequivalents of Na excreted in 24 hours in the urine.

Dehydration.

This can be caused by excess renal loss with high positive free water clearance (i.e., loss of water in excess of NaCl), excess sweating and low water intake. The serum sodium is elevated, as is the hematocrit (possibly masking a true anemia), and the urine sodium is also high due to increased renal excretion of NaCl.

Diabetes insipidus (DI).

DI may be central (neurogenic) (i.e., due to decreased vasopressin secretion) or nephrogenic (i.e., due to decreased renal response). Functionally, this condition is the reverse of SIADH, i.e., water retention in the tubules is not adequate. While this condition is not completely understood, and may be multifactorial, current research suggests that either mutation and/or changes in protein expression of ‘water channel molecules’ (renal aquaporins) and/or the vasopressin V2 renal collecting tubule cell receptor may play a role in both pathological water loss, such as in nephrogenic DI, and pathological water retention, such as in SIADH. The pattern is elevated serum sodium but dilute urinary sodium due to the functionally inadequate levels of ADH.

Hyperaldosteronism.

This condition may result from adrenal hyperplasia, Cushing's syndrome and Cushing's disease. The levels of circulating aldosterone are inappropriately high, causing excessive reabsorption of Na and excretion of K⁺ and H⁺ ions. The patient will be hypernatremic and hypokalemic and exhibit a mild metabolic alkalosis.

Hypokalemia

Many of the causes of hypokalemia overlap with those of hyponatremia including overhydration; use of loop diuretics; SIADH; and Bartter's syndrome, as discussed above. In addition to these causes overlapping with those of hyponatremia, there are the following states that lead uniquely to hypokalemia.

	1.	Infusion of insulin to diabetics. This results in rather large influxes of potassium into cells, lowering it in serum.
	2.	Alkalosis. Red blood cells are themselves excellent buffers. They are capable of exchanging potassium for hydrogen ions. Thus, in acidosis, H+ ions enter red cells in exchange for K+ ions. Conversely, in alkalosis, H+ ions leave red cells (to neutralize excess base) while K+ ions enter the red cells.
	3.	Vomiting. The major loss is both H+ and K+ from the stomach.

Hyperkalemia

Among the major causes are those that also cause hypernatremia, e.g., dehydration and diabetes insipidus, and, additionally, the following: acidosis and diabetes mellitus (as discussed above); and hemolysis. Any kind of cell damage, such as rhabdomyolysis, and especially hemolysis of erythrocytes, can cause hyperkalemia. In hemolysis, all of the intracellular K⁺ is extruded into plasma. Another analyte that is concentrated in red cells that rises with K⁺ in hemolysis is lactate dehydrogenase (LD). Concomitant elevations of potassium and LD in serum should be taken as indications of hemolysis either artifactually after a blood sample has been taken from the patient or, less commonly, hemolysis from an underlying hemolytic condition.

(Source: McPherson & Pincus: Henry's Clinical Diagnosis and Management by Laboratory Methods, 21st ed.)