Effects of alcohol on electrolytes and minerals
Effects of Alcohol on Electrolytes and Minerals
Electrolytes and minerals are involved in most cellular activities and assume a major role in metabolism. They have multiple functions such as holding fluids in compartments of the body and maintaining normal acid-base balance. Electrolytes as sodium, potassium, and chloride can dissociate into positively and negatively charged particles capable of conveying electrical impulses. Thus, dissolving sodium chloride, commonly known as table salt, in water separates the electrolyte into sodium (positively charged) and chloride (negatively charged). Positively charged (metallic) elements in the diet often are referred to as minerals. With the exception of phosphate, all of the nutrients cited in this article bear a positive charge.
Alcohol consumption, both chronic and acute, has major effects on the absorption, elimination, and serum concentrations of many physiologically important electrolytes and minerals, including sodium, potassium, phosphorus, calcium, magnesium, iron, zinc, and selenium (Beard et al. 1979; Harris et al. 1979; Arieff and Papadakis 1988; Knochel 1988; and McClain et al. 1986). Electrolyte disturbances may lead to severe and even life-threatening metabolic abnormalities. This article provides a clinical overview of the effects of acute and chronic alcohol intake, as well as of liver disease, on these electrolytes.
Sodium and Water Balance
A close relationship exists between the metabolism of water and that of sodium. Sodium is the primary electrolyte present in body fluids outside the cells, with only about 5 percent of the sodium concentration of the body occurring intracellularly. This electrolyte, together with potassium, assists in the maintenance of the body’s electrolyte and water balance. In addition, potassium and sodium play an important role in nerve conduction, muscle contraction, and the transport of substances across membranes.
Only one-third of the body’s water, however, is outside the cells (Levinsky 1987). The presence of water in the body is essential for the performance of many physiological functions. Water helps to equilibrate and maintain body temperature; provides moisture to the surfaces of the lungs; furnishes a medium for digestion, absorption, and metabolism; and acts as a solvent for the other materials in the cell.
Because a close relationship exists between the metabolism of water and sodium, changes in the fluid volume inside vessels and around the cells–fluid that consists mainly of water and sodium salts–may have a major impact on serum sodium concentrations.
Alcohol consumption can have pharmacological effects on water and sodium metabolism. The effects of alcohol on sodium and water balance may differ with acute alcohol intake, chronic alcohol intake, or acute withdrawal from chronic alcohol abuse.
As the blood alcohol level rises with acute alcohol intake, a transitory increase in the elimination of “free water” (water without salts) by the kidney occurs (Rubini et al. 1955), resulting from inhibition of the release of antidiuretic hormone (ADH). As the plasma alcohol level decreases, urinary flow is reduced (Nicholson and Taylor 1938). Concomitant stimulation of water intake (Sargent et al. 1978) causes significant water gain. This water retention occurs together with sodium retention (Nicholson and Taylor 1938; Sargent et al. 1978) due to increases in the reabsorption of sodium by the kidney.
Animal studies involving chronic alcohol intake have shown significant retention of water, sodium, potassium, and chloride after the first week of daily alcohol ingestion (Beard and Knott 1968). Urine output does not decrease, but fluid ingestion is stimulated.
During acute withdrawal following chronic alcohol abuse, urinary elimination of sodium, chloride, and water increases (Beard and Knott 1968). The augmented urinary flow eliminates the fluid and electrolytes that were retained in excess during alcohol abuse.
Low Serum Sodium (Hyponatremia)
Factors other than the direct pharmacological effects of alcohol can alter sodium and water balance, modifying the final serum sodium concentration. Disorders that diminish the volume of fluid in vessels and other extracellular spaces occur frequently in alcoholics, and can produce low serum sodium. Among these disorders are diarrhea, due to alcohol ingestion; vomiting, attributable to stomach irritation; excessive urination, due to poor control of glucose (in alcoholics with diabetes); and excessive perspiration, because of alcohol withdrawal or fever.
Alcoholics with liver disease frequently have abnormal sodium serum concentrations, with hyponatremia (low plasma sodium concentration) as the most common alteration. In this condition, the low sodium concentration results from “dilution” (Edelman et al. 1958), with normal or increased amounts of sodium offset by greater increases in the total volume of water. The increase in the volume of water and sodium in the body finally is expressed as edema or ascites (fluid accumulation in the abdomen).
Several factors may contribute to the diminished concentration of sodium observed in alcoholics with liver disease: * the kidneys’ ability to eliminate “free
water” becomes impaired; * elevated levels of antidiuretic
hormone increase the efficiency of
water retention by the kidney
(Bichet et al. 1982); * diminished total body content of
potassium indirectly affects sodium
plasma concentration (Edelman et al.
1958); and * use of such medications as diuretics
or laxatives (Ashraf et al. 1981)
causes an increase in urinary and fecal elimination of sodium and water, which can result in low
sodium concentrations when the
excreted fluids are replaced with
It is important to understand that hyponatremia often occurs in conjunction with total body sodium excess in alcoholics who have liver disease. The sodium concentration abnormality usually develops very slowly. It frequently is asymptomatic and of limited clinical significance, except for the presence of edema or ascites, of which both are related to the total body sodium excess.
The decrease in serum sodium, however, can have important clinical implications. When this decrease occurs rapidly, swelling of the brain may develop, leading to confusion, lethargy, and seizures. When the decrease in serum sodium occurs slowly, the low sodium content in the brain causes a reduction in both brain energy metabolism and the release and reuptake of certain amino acids that serve as chemical messengers within the brain (Fraser et al. 1987), processes that require sodium. It has been suggested that these metabolic changes may be responsible, at least in part, for the neuropsychiatric changes in patients with severe liver disease (portal systemic encephalopathy).
A low serum sodium concentration also has prognostic importance. In a study by Arroyo and associates (1976), the fatality rate for patients with hyponatremia and impaired kidney function was 62 percent; 3.4 times greater than that of patients without a low-sodium condition.
High Serum Sodium (Hypernatremia)
Hypernatremia (increased serum sodium concentration) occurs less frequently in liver disease and, in most cases, is due to such medical interventions as diuretics or lactulose therapy. Increased serum sodium concentration may develop from alterations in several physiological activities and functions. Hypernatremia may result from excessive loss of “free water.” In addition, hypernatremia can result if sodium and water levels increase, but sodium increases with a greater magnitude. Conversely, if sodium and water losses increase, but water loss is proportionately greater, high serum sodium concentrations can result. The latter cause occurs more frequently and is seen, for example, after use of excessive lactulose therapy for portalsystemic encephalopathy (Warren et al. 1980; Nelson et al. 1983).
Lactulose is a nonabsorbable sugar that makes the stools moderately acidic, thus decreasing the production and absorption of toxic ammonia from the intestine. Unfortunately, this laxative also causes large losses of water that contains little sodium, thereby increasing the concentration of the sodium remaining in the body.
Excessive loss of water by perspiration or rapid breathing in patients unable to drink adequate amounts of water is another important cause of hypernatremia.
The signs and symptoms of high serum sodium include intense thirst, lethargy, stupor, coma, muscle irritability, and seizures. Serum sodium levels above 145 milliequivalents per liter (mEq/1) in cirrhosis indicates poor prognosis, with a hospital mortality rate of more than 80 percent.
Low Serum Potassium (Hypokalemia)
Unlike sodium, potassium is predominantly an intracellular electrolyte. Low serum potassium frequently is observed in hospitalized alcoholics. It is often difficult to determine whether low serum potassium reflects a deficit in total body potassium or merely a shift of potassium from the extracellular fluid into the cells. In alcoholics with liver disease, low serum potassium may result from poor nutritional intake; decreased muscular mass; loss due to nausea, vomiting, or diarrhea; or the use of diuretics to control edema or ascites.
Various factors may shift potassium from the extracellular fluid into the cells, thereby decreasing serum potassium concentration. These factors, which are observed frequently in alcoholics and are independent of the presence or absence of liver disease, include: * respiratory alkalosis, an alkaline
condition of the blood resulting from
excessive elimination of carbon
dioxide by the lungs (Burnell et al. 1956); * elevated insulin levels (Harter et al.
1976); and * elevated epinephrine levels resulting
from alcohol withdrawal
Low serum potassium can produce a multitude of serious consequences, such as muscular weakness, destruction of muscle fibers, gut paralysis, heartbeat abnormalities, and even death through cardiac arrest.
Because of the very serious and potentially life-threatening outcome of low serum potassium, it is important to detect this disorder early and to correct it quickly and carefully. Intense intravenous potassium replacement may be necessary, but the response to each replacement dose should be monitored closely.
High Serum Potassium (Hyperkalemia)
Elevated levels of serum potassium in alcoholics and in liver disease occur less frequently than do diminished serum potassium levels, and, when present, usually are due to the use of medications or to kidney failure. One important cause of hyperkalemia is the use of potassium-containing salt substitutes concomitant with the use of diuretics that spare potassium. Potassium also can be released into the blood as a result of muscle cell destruction (rhabdomyolysis), a potential complication observed in alcoholics.
Patient X is a 54-year-old male with a 15-year history of severe alcohol abuse. He was evaluated by his physician and was found to have edema of the lower extremities and severe ascites. The patient had normal electrolytes (sodium, potassium, and chloride) at that time. Hydrochlorothiazide, at 50 milligrams (mg) per day, a diuretic causing sodium and potassium loss, was prescribed.
Two weeks later, the patient arrived at the emergency room, disoriented and lethargic. He had mild edema and moderate ascites, with low sodium and potassium levels. The patient was treated with water restriction (800 cc/ day) and oral potassium chloride supplements. He also was given lactulose to treat his abnormal mental status, which may have resulted in part from the low levels of sodium and potassium. His mental status improved after lactulose therapy and replacement with potassium chloride, and his serum sodium normalized slowly. He was discharged 1 week later on a 1 gram (g) sodium diet and spironolactone, a diuretic that conserves potassium.
In followup 2 weeks later, the patient’s electrolytes were normal. He had no peripheral edema and only a mild amount of ascites. Four days after this, he read in a health magazine that salt substitutes might improve the flavor of his diet, so he started to use a potassium-rich salt substitute. One week later, his potassium level was abnormally high. The patient was treated for his hyperkalemia and advised not to use potassium-containing salt substitutes.
Low Serum Phosphate (Hypophosphatemia)
Phosphate, a constituent of bones and teeth, is an integral part of many of the structural and functional molecules of the body. Low serum phosphate frequently
occurs in hospitalized patients who have severe alcohol-related problems as a result of poor dietary intake (Lotz et al. 1968), increased urinary losses (Miller et al. 1978), or respiratory alkalosis resulting from intense breathing (Mostellar and Tuttle 1964). The phosphate concentration usually is slightly depressed at the time of hospital admission, but may become dangerously low after administration of calories to the patient. Feeding exacerbates low serum phosphate through a resulting increase in insulin levels, thus promoting the transfer of phosphate from the bloodstream into the cells (Miller et al. 1978). Magnesium deficiency also may cause phosphorus deficiency in skeletal muscle (Whang and Welt 1963), because magnesium and phosphorus metabolism are interrelated.
Phosphate deficiency and slowly developing hypophosphatemia are manifested clinically as irritability, apprehension, confusion, seizures, coma, oxygen starvation in tissues, and destruction of muscle cells. Because hypophosphatemia frequently goes unrecognized, it is important to monitor closely serum phosphate levels in alcoholic patients at their initial evaluation, and in the days following admission. Early detection and treatment of hypophosphatemia is imperative to prevent its potentially serious consequences.
Acute and chronic administration of alcohol and withdrawal from chronic alcohol consumption affect serum concentrations of calcium. A major constituent of bones and teeth, calcium is required for blood clotting, muscle contraction, and nerve transmission. Acute alcohol administration increases urinary excretion of calcium twofold in both alcoholics and nonalcoholics, yet serum calcium concentration (Kalbfleisch et al. 1963), or intestinal absorption of calcium, is not altered.
Chronic alcohol consumption decreases serum calcium concentration and urinary calcium excretion after several days (Ogata et al. 1968). Withdrawal from chronic alcohol consumption can cause a slight decrease in serum calcium concentration, with a normal or slightly elevated excretion of calcium in the urine (Sullivan et al. 1969). The interrelationship between calcium and magnesium metabolism, discussed below, allows for the correction of low serum calcium with magnesium administration.
Low Serum Calcium (Hypocalcemia)
Low serum calcium (hypocalcemia) is common in patients with severe alcoholism and liver disease. Manifestations of low calcium include muscle twitching and spasms, tingling, numbness, seizures, heart block, and abnormal heart rhythms.
Several factors account for the association between occurrence of hypocalcemia and severe alcoholism. Calcium in the blood is bound to the protein, albumin. In alcoholics, poor diet or liver disease results in diminished albumin levels, thereby limiting the amount of calcium that can remain dissolved in the blood.
Decreased parathyroid hormone activity also contributes to the development of low serum calcium. This hormone, which is secreted by the parathyroid glands (in the neck), regulates serum calcium concentration. It normally responds to low serum calcium levels by mobilizing calcium from bone and pumping it into the bloodstream. Low magnesium levels, common in alcoholics (see below), blunt the sensitivity of the parathyroid gland to low calcium levels (Estep et al. 1969). Thus, the gland fails to secrete additional hormone when the serum calcium level drops.
Finally, low calcium levels may result from a deficiency of vitamin D, necessary for adequate absorption of calcium from the gut. (Fat malabsorption is common in alcoholics, resulting in poor absorption of vitamin D and other fat-soluble vitamins; see the article by Feinman, pp. 207-210.) Fat that is not absorbed forms insoluble soaps with calcium within the intestine, decreasing further the amount of available calcium.
Magnesium is an important constituent of bones and teeth. It also assists enzymes involved in cellular energy production and protein digestion, and plays a role in the transmission of impulses in nerves.
Acute administration of ethanol increases urinary excretion of magnesium (Kalbfleisch et al. 1963) without affecting serum magnesium concentration (Ogata et al. 1968). Chronic ethanol consumption can cause a fall in serum and red blood cell magnesium concentration (Hines 1975) because of urinary losses of magnesium that exceed magnesium absorption.
After 24 hours, withdrawal from chronic ethanol consumption causes a transitory decrease in serum magnesium concentrations and red blood cell magnesium (Hines 1975) that can be corrected with a few days of normal diet.
Low Serum Magnesium
Low serum magnesium (hypomagnesemia) frequently is detected in the hospitalized chronic alcoholic. The manifestations of low serum magnesium can be severe and include tremor, muscular twitches and cramps, convulsions, apathy, depression, agitation, confusion, abnormal heart rhythm, and even cardiac arrest.
Hypomagnesemia may result from inadequate intake, poor absorption (due to fat malabsorption), increased urinary loss, or diarrhea. Refeeding also may cause hypomagnesemia, as magnesium shifts from the bloodstream to the spaces between cells to participate in reactions that form and store energy.
TRACE ELEMENT ABNORMALITIES
Iron is an important component of hemoglobin and is involved in a variety of enzyme systems. Both excesses and deficiencies of iron can occur in patients with chronic alcoholism.
The occurrence of iron overload is well documented in patients with alcoholic liver disease. Some investigators speculated initially that hemochromatosis (a genetic disease of iron overload) was caused by chronic alcohol ingestion. Recent studies, however, demonstrate clearly that while patients with alcoholic liver disease have mild to moderate iron excess in the liver, this excess is not nearly as great as that seen in patients with genetic iron overload (Bassett et al. 1986). Why some patients with alcoholic liver disease develop excess iron in their liver, and whether this iron causes further liver damage, remains to be determined.
Conversely, iron deficiency anemia is common in alcoholics as a result of blood loss due to esophagitis, gastritis, duodenal ulcers, or esophageal varices. Furthermore, alcoholics who have had part of their stomach removed because of ulcer disease can develop iron deficiency anemia due to poor absorption of iron. Thus, alcoholics may have either iron excess or iron deficiency, depending on the clinical situation.
Patient A is a 53-year-old with alcoholic cirrhosis who developed bleeding from esophageal varices. Varices, dilated veins that bleed easily, resemble ropes running down the esophagus (Figure 1). These varices were injected with a sclerosing agent that caused the bleeding to stop, and the patient did well. Patient B is a social drinker who used alcohol on a regular basis and was taking ibuprofen for musculoskeletal cramps. The combination of this non-steroidal anti-inflammatory agent and alcohol produced a stomach ulcer with resulting gastrointestinal blood loss that eventually caused an iron-deficiency anemia. Figure 2 shows the ulcer in a healing stage.
Zinc, an essential trace element required for RNA and DNA synthesis and for the function of more than 200 enzymes, also plays an important role in membrane stabilization. Zinc deficiency causes a progressive increase in membrane fluidity.
Zinc deficiency is a frequent occurrence in alcoholism, with or without liver disease, that has important and correctable complications. Vallee and associates (1956) reported the occurrence of marked hypozincemia (low serum zinc) in severe alcoholic cirrhosis. Other researchers have confirmed this observation, and depressed concentrations of zinc in the liver, white blood cells, pancreatic juice, and testes also have been reported in alcohol cirrhotics, as well as in some patients treated for acute and chronic alcoholism without liver disease. Similarly, rats fed alcohol in their water supply developed hypozincemia. Thus, it is clear that alcoholics, with or without liver disease, are at risk for the development of zinc deficiency (McClain et al. 1986).
Decreased intake, increased urinary excretion, and poor absorption of zinc, factors common in alcoholics, account for hypozincemia. Potential clinical complications of zinc deficiency in the chronic alcoholic include crusting skin lesions, hypogonadism, impaired night vision, anorexia, depressed immune function, altered mental status, impaired protein metabolism and wound healing, diarrhea, depressed mental function, and, possibly, birth defects as related to the fetal alcohol syndrome. Zinc supplementation reportedly can improve night vision, immune function, and taste sensation in alcoholics.
A 56-year-old man was admitted to a hospital for progressive abdominal pain, nausea, and vomiting. Previously, the patient had undergone gastric surgery involving the removal of a portion of his stomach for a duodenal ulcer. Over the past 3 months, he had consumed alcohol almost exclusively, because ingestion of solid food led to vomiting. At the time he was brought to the hospital, he could not tolerate even liquids.
The patient was given intravenous fluid support. He developed a severe rash around the eyes, nose, and mouth. The rash, known as acrodermatitis, is typical for zinc deficiency. His serum zinc level was depressed markedly. Five days of oral zinc supplementation corrected the skin changes entirely.
Selenium is a trace element required for the activity of the enzyme glutathione peroxidase, a component of the antioxidant system that protects cells against certain harmful effects that are believed to be mediated by alcohol (see the article by Lieber, pp. 197-205). Decreased serum selenium levels have been reported by a variety of investigators in cases of chronic alcoholism without liver disease, and, to a greater extent, in patients with alcoholic liver disease (Valimaki et al. 1983). Alcohol intake over short periods of time did not decrease selenium levels in healthy volunteers, nor did abstinence for a 2-week period increase selenium levels in chronic alcoholics. Several investigators have shown correlations between albumin levels or other indicators of liver function, and serum selenium levels.
Selenium deficiency has been shown to cause abnormalities of skeletal and heart muscles in man, and has been associated with liver and pancreatic degeneration as well as various muscular diseases in animals. The possibility that decreased selenium and selenium glutathione peroxidase activity may potentiate some of the other injurious effects of alcohol has not yet been investigated.
Altered metabolism of a variety of electrolytes and trace metals can occur in alcoholism, both with and without alcoholic liver disease. Nutrient deficiencies can develop for a variety of reasons, including poor intake, impaired absorption, and increased excretion. Some of these deficiencies, such as low potassium, sodium, or magnesium levels, may cause such life-threatening problems as cardiac arrhythmias or seizure activity. Thus, it is important for all health care workers to be aware of the electrolyte and mineral disturbances that can occur in association with alcohol intake.
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