Using ABG samples to determine electrolyte levels can aid in quickly and accurately evaluating acid-based disorders.

Complete assessment of acid-base disorders requires a stepwise approach that includes analyzing electrolyte levels and determining the anion gap and pH. Modern blood-gas analyzers offer the option of measuring electrolytes using part of the arterial blood gas (ABG) sample. These multifunction analyzers can broaden understanding of the electrolyte contribution to metabolic derangements in acid-base disturbances. The RCP is often both the provider and the first interpreter of these data.

Technical Considerations
Electrolyte analysis as part of ABG testing offers distinct advantages. The current practice of many intensive care units in locating the ABG analyzer within or in proximity to the unit ensures timely results. Electrolyte determination provides the complete picture of acid-base derangement. This can add key insight during difficult diagnoses. In neonates, collection of a single capillary sample is likely to preserve blood volume and can reduce the need for sampling in patients without indwelling lines. Although a low bicarbonate level, when seen in the results of automated serum-chemistry testing, is often the first clue to the presence of metabolic acidosis, it should not be considered diagnostic. A low bicarbonate level shown in a serum-chemistry report can be due to metabolic acidosis, a metabolic compensation for respiratory alkalosis, or a laboratory error. The bicarbonate calculations of an ABG analyzer using the Henderson-Hasselbalch equation probably represent a more correct measure of plasma bicarbonate. Measurement of Pco2 using ABG analysis in a patient with a low bicarbonate level allows differentiation between respiratory alkalosis and primary metabolic acidosis. Because the analysis method can influence later calculations, the bicarbonate level used to calculate the anion gap should be the result of ABG analysis, not automated serum-chemistry evaluation.

Traditionally, electrolyte analysis is performed on serum, the portion of blood without cells or clotting factors. Serum is used to eliminate any ionic contribution that hemolyzed cells might make to the sample. Potassium, in particular, is stored primarily within the cell; this presents a problem in analyzing whole-blood samples that have undergone hemolysis, which releases potassium from the cell and can cause a falsely elevated value. Factors that can cause hemolysis in a sample include small needle size, rough handling, incorrect temperature, and elapsed time. Obtaining the sample and performing analysis without delay minimize the influence of hemolysis on results.

A second technical concern is the use of sodium heparin to prevent clotting. This leads to falsely elevated sodium values. Fortunately, it is easily remedied through the use of lithium heparin, which is available in many commercial kits. Other anticoagulants, such as sodium citrate or ethylenediaminetetraacetic acid (EDTA), are also contraindicated; they, too, can lead to errors in electrolyte determination.

Consequences of Acid-Base Derangement
Acidosis can decrease cardiac contractility in direct proportion to the decrease seen in pH. Both metabolic and respiratory acidosis cause similar degrees of myocardial depression, but the effect of the latter may be more rapid, probably because of the rapid entry of carbon dioxide into cardiac cells. Although metabolic acidosis decreases the threshold for ventricular fibrillation in animals, no clinical increase in arrhythmias is usually seen. Acidosis also causes stimulation of the sympathetic-adrenal axis, and in severe acidemia, this effect is countered by depressed responsiveness of the adrenergic receptors to circulating catecholamines (such as dopamine).

Acute respiratory acidosis causes marked increases in cerebral blood flow. Acute elevation of the Pco2 level to more than 60 mm Hg causes confusion and headache. When it exceeds 70 mm Hg, loss of consciousness and seizures can occur. Chronic elevations in carbon dioxide, however, are typically well tolerated, even when their level is as high as 150 mm Hg.

Acute hypercapnia causes depression of diaphragmatic contractility and a decrease in endurance. The effect of metabolic acidemia on the respiratory muscles is less clear, but it probably causes depression of contractility.

The effects of acidemia on electrolyte levels are quite complex. Acute infusions of hydrochloric acid have been shown to cause an increase in serum potassium, but the administration of organic acids (such as lactic acid and keto acids) does not raise potassium levels. The hyperkalemia commonly observed in both lactic acidosis and ketoacidosis is due to factors other than the pH change. Acute respiratory acidemia causes no change, or a slight increase, in serum potassium levels.

Alkalosis appears to increase myocardial contractility, at least up to a pH of 7.7. It seems to have little effect on the threshold for ventricular fibrillation. Hyperventilation can also cause a decrease in systemic vascular resistance, although alkalosis can cause coronary artery spasm where there is electrocardiographic evidence of ischemia. Acute respiratory alkalosis causes a decrease in cerebral blood flow (an effect that is only transitory). It produces confusion, myoclonus, asterixis, loss of consciousness, and seizures. Acute hypocapnia causes a slight reduction in serum levels of sodium and potassium. Alkalosis also causes an increase in hemoglobin’s affinity for oxygen; there is, however, also an increase in the concentration of 2,3-diphosphoglycerate in red blood cells, as well as a change in its morphology. Both can oppose the increased oxygen affinity, so the clinical effect of alkalosis-induced changes in oxygen delivery appears to be minimal.

Variations in pH alter the degree of ionization of proteins and many drugs. As most ionized substances do not cross cell membranes readily, alterations in pH affect both cellular function and the potency of many pharmaceutical agents. Relative acidity of tissues (for example, in the vicinity of an abscess) is recognized as reducing the efficacy of local-anesthetic solutions. Conversely, relative alkalinity enhances their uptake. Alkalinity also potentiates drugs such as meperidine and morphine by increasing the amount of lipophilic, uncharged base available to cross the blood-brain barrier.

The concentration of free acid produced in body fluids increases as metabolic processes accelerate. The free acid may be volatile or nonvolatile, with volatility determined by the ability of the body to reduce acid concentrations by increasing ventilation. Carbon dioxide is the principal volatile acid and is usually eliminated as quickly as it is produced. Carbon dioxide as acid is transported in the blood in two ways; it can dissolve directly into plasma or be bound to hemoglobin. Of carbon dioxide in the plasma, 90% is transported as bicarbonate. In the red blood cell, carbon dioxide is first converted to H2CO3 by carbonic anhydrase. It then reverts to bicarbonate plus a hydrogen ion. The bicarbonate leaves the red blood cell in the veins and is exchanged for a chloride ion. This interconversion is known as the chloride shift, and it is responsible for the higher chloride content of venous blood, as compared with arterial blood. The bicarbonate then travels to the lungs, where carbonic anhydrase converts it back into carbon dioxide. This process constitutes the bicarbonate/carbon dioxide buffer, which provides 45% of the body’s buffering capacity. The plasma bicarbonate can respond instantly to a higher acid load via increased ventilation. This shift ensures that moderate changes in plasma ions will not lead to acid-base disturbances. The remaining buffers are the intracellular proteins, phosphates, and bone. It is only when these buffering systems are overwhelmed that systemic alkalosis or acidosis is possible. Normally, the renal tubule cells in almost all parts of the nephron generate and secrete protons (H+) into the tubule lumen. Protons are generated inside the tubule cell in the process of carbon dioxide hydration, which is catalyzed by carbonic anhydrase: carbon dioxide plus water to H2CO3 to H+ plus bicarbonate.

In the tubule lumen, the secreted proton may combine with bicarbonate, ammonia, or HPO4 (phosphate). Thus, proton secretion serves to resorb (save) the filtered bicarbonate and to excrete the nonvolatile acid in the form of ammonium and titratable acids (mainly H2PO4 [phosphatidic acid]). In chronic acidosis, the capacity of the kidney to produce ammonia/ammonium and excrete fixed acids is increased as much as fourfold.

The buffer bases in the tubule fluid (mainly ammonia and HPO4) permit the excretion of fixed acids without excessive lowering of the tubule fluid’s pH.

For each proton excreted in the form of titratable acid, one bicarbonate molecule is added to the blood. This new bicarbonate replenishes the body’s store of buffer base. Under steady-state conditions, bicarbonate is generated by the kidney at the same rate at which it is consumed in the process of buffering the fixed acids produced by metabolism. The role of the kidney in acid-base balance is to maintain adequate levels of buffer bases in the body. When there is a deficit, the kidneys generate new bicarbonate in the process of acid excretion. When there is an excess of bicarbonate (as seen in patients receiving no-protein diets or being given citrate with blood transfusions), the healthy kidney eliminates bicarbonate in the urine.

The rate of proton secretion by the tubule cells is related to the degree of intracellular acidosis. Furthermore, as the acidosis becomes chronic, the production and secretion of ammonium can increase to as much as four times the normal rate. Consequently, given normal renal function, nonvolatile acid excretion and bicarbonate generation during acidosis are increased several times. In chronic renal failure, the capacity of the remaining nephrons to excrete acid and generate bicarbonate is also increased many times. The number of these functioning nephrons, however, may not be sufficient to maintain acid-base balance, causing the development of metabolic acidosis.

The Physiologic Role of Individual Ions
In reviewing how acid-base levels are affected by changes in electrolyte levels, it is important to focus on the roles that these ions play in normal renal physiology. The significance of each ion is the part that it plays in regulating bicarbonate balance

Sodium is the chief extracellular cation. It plays an integral role in the proper function of muscles and in nerve conduction. In the plasma, sodium is usually paired with chloride. Much of kidney function is based on the absorption or excretion of sodium. Sodium is excreted from the cells of proximal convoluted tubules in exchange for potassium. This creates a sodium gradient that draws sodium into the cells and then into the blood. The thick arm of the loop of Henle relies on this gradient to draw potassium and chloride out of the tubules by cotransport with sodium. The distal convoluted tubule has transport systems that rely on sodium gradients to transport potassium and hydrogen and, hence, to influence pH in the blood.

Like sodium, potassium plays a role in muscle contraction and nerve action. Normally, potassium is found at very low levels in the plasma, and has little effect on plasma acid-base levels. When serum potassium levels are elevated, dangerous arrhythmias can lead to cardiac failure. Less dangerous arrhythmias can also occur if plasma potassium is diminished.

In the kidney, potassium can be exchanged for sodium or transported with sodium and chloride. In the distal convoluted tubule, potassium competes with hydrogen ions for countertransport with sodium. When there is plasma acidosis, increased hydrogen will be exchanged for sodium and less potassium will be excreted. This will lead to elevated potassium levels in the plasma. When the blood is alkalotic, less hydrogen is available for exchange with potassium; therefore, potassium is a more successful competitor than hydrogen, and more potassium enters the tubules in exchange for sodium. This leads to increased excretion of potassium and diminished hydrogen excretion. Reflexively, this leads to diminished absorption of bicarbonate into the blood.

Chloride is an anion paired with sodium in the plasma. Chloride plays an inhibitory role in neuronal action. In the kidneys, chloride is transported with sodium and potassium in the ascending loop of Henle.

Calcium ions are found in quantity in intracellular stores, and also in the plasma. Calcium is important in muscular contraction, in the makeup of bones, and in many neuronal activities, including learning. While calcium’s effects on acid-base physiology are minimal, plasma calcium ion levels can be affected by blood pH. When the plasma becomes acidotic, calcium begins to precipitate and form solid crystals. This can lead to decreased plasma calcium levels, and it accounts for the difference in venous and arterial calcium levels.

Ions and their roles in the kidney are also important in metabolic alkalosis. Metabolic alkalosis can be caused by improper levels of plasma electrolytes and can be made worse by renal attempts to compensate. Decreased levels of potassium, acting in concert with increased levels of aldosterone, can lead to greater excretion of protons in the collecting ducts. This comes with increased ammonium release into the blood, and it must be compensated for by increased bicarbonate secretion. This, in turn, leads to a spiraling increase in plasma pH, the continued loss of protons being coupled with the increase in plasma bicarbonate.

The Anion Gap
While individual ions’ contributions to acid-base physiology may not be significant, they can be indicative of other metabolic disturbances. When considered together, they are a powerful tool for acid-base analysis. Sodium, potassium, chloride, and bicarbonate make up most of the charged particles in the plasma, but there are other charged compounds for which levels are not determined during analysis. Measured serum cation levels are higher than measured anion levels, and this disparity is known as the anion gap. Serum proteins, phosphates, and sulfates contribute to the normal anion gap of 12 to 18 mEq/L.

There are two ways to calculate the anion gap for an ABG sample. The first method involves adding the sodium and potassium levels, then subtracting the sum of the chloride and bicarbonate levels. Since potassium contributes so little to normal plasma levels, it can actually be omitted from the calculation of the anion gap, leaving sodium as the lone cation.

The anion-gap calculation allows the differentiation of two types of metabolic acidosis. The first, metabolic acidosis with a large anion gap, is associated with the addition of nonvolatile acids, endogenously or exogenously generated. The second, metabolic acidosis with a normal anion gap, is associated with the loss of bicarbonate or with failure to excrete H+ from the body. When the body produces altered levels of ketones and other anions, there is a reflexive shift in the measured levels of bicarbonate. Bicarbonate’s role as a buffer is central to this process and ensures that bicarbonate levels will decrease when other anions are added. When bicarbonate’s buffering ability is overcome, this shift will lead to the decreased plasma pH of metabolic acidosis. The kidney attempts to compensate for the decreased bicarbonate levels by increasing the activity of endogenous carbonic anhydrase in the proximal tubules. This leads to increased production of bicarbonate in the kidney and increased hydrogen excretion in the urine.

The causes of a large anion gap are primarily lactic acidosis, renal failure, salicylates, ketones, methanol, formaldehyde, ethylene glycol, paraldehyde, sulfates, and massive rhabdomyolysis.

A normal anion gap (hyperchloremic acidosis) can be seen in association with gastrointestinal loss of bicarbonate (pancreatic fistula), diarrhea, renal bicarbonate loss, hypoaldosteronism, hyperventilation, ammonium chloride, acetazolamide, hyperalimentation fluids, and some cases of ketoacidosis (particularly during insulin treatment).

The anion gap can enlarge as a result of increases in unmeasured anions or decreases in unmeasured cations (such as hypokalemia, hypocalcemia, and hypomagnesemia). The anion gap can also widen as a result of an increase in albumin or in negative charges on albumin.The anion gap can be decreased by an increase in unmeasured cations (such as hypercalcemia, hypermagnesemia, lithium intoxication, and high immunoglobulin G levels) or a decrease in unmeasured anions (hypoalbuminemia). Laboratory errors can also affect anion-gap calculations, and hyperproteinemia and hyperlipidemia (resulting in the underestimation of serum sodium) can falsely narrow the anion gap. In addition, bromide intoxication can be mistaken for serum chloride, resulting in inappropriately small anion-gap estimates.

Case example
A 24-year-old male was seen by the emergency department for seizures and coma. He was reportedly seen drunk several hours earlier. His heart rate was 93 beats per minute, and his respiratory rate was 30 breaths per minute. His blood pressure was 160/100. ABG and electrolyte analysis indicated a pH of 7.17, a PaCO2 of 25 mm Hg, a PaO2 of 80 mm Hg, a bicarbonate level of 10 mmol/L, a sodium level of 141 mmol/L, a potassium level of 4.5 mmol/L, and a chloride level of 101 mmol/L. The anion gap was 33.5.

This patient presented with metabolic acidosis and a large anion gap (with partial respiratory compensation). This suggested the presence of nonvolatile acid in the blood. Later urinalysis revealed the presence of oxalate crystals. This, along with a history of drunkenness, suggested ethylene glycol poisoning. Ethylene glycol is metabolized to glycolic and oxalic acid, causing the profound acidosis seen in this case.

The addition of electrolyte determination to ABG measurements provides new tools for the RCP’s use in acid-base evaluation. Determining electrolyte levels using ABG samples may provide advantages over using separate tests. The ability to determine the anion gap quickly may give the RCP new insights into the cause of metabolic acidosis and lead to more rapid treatment. N
Kelvin D. MacDonald, RRT, is a respiratory care practitioner at Kaiser Permanente Hospital in Los Angeles. He and Christopher Cockerham are both second year medical students at Saba University School of Medicine, Saba, Netherlands-Antilles.

Reading List
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