CHAPTER 139
Minerals and Electrolytes
Minerals are necessary for the normal functioning of the body’s cells. The body needs large quantities of calcium, chloride, magnesium, phosphate, potassium, and sodium. These minerals are called macro-minerals. Bone, muscle, heart, and brain function depends on these minerals. The body needs small quantities of chromium, copper, fluoride, iodine, iron, manganese, molybdenum, selenium, and zinc. These minerals are called trace minerals. Except for chromium, all trace minerals are incorporated into enzymes or hormones required in body processes (metabolism). Chromium helps the body keep blood sugar levels normal. All trace minerals are harmful if too much is ingested.
Minerals are an essential part of a healthy diet. The recommended dietary allowance (RDA)—the amount most healthy people need each day to remain healthy—has been determined for most min-erals. People who have a disorder may need more or less than this amount.
Consuming too little or too much of certain minerals can cause a nutritional disorder. People who eat a balanced diet containing a variety of foods are unlikely to develop a nutritional disorder or a major mineral deficiency, except for calcium, iodine, or iron deficiency. However, people who follow restrictive diets may not consume enough of a particular mineral (or vitamin). For example, vegetarians, including those who eat eggs and dairy products, are at risk of iron deficiency. Infants are more likely to develop deficiencies because they are growing rapidly (thus requiring large amounts of nutrients).
Consuming large amounts (megadoses) of mineral supplements without medical supervision may have harmful (toxic) effects.
Electrolytes: Some minerals—especially the macro-minerals—are important as electrolytes. The body uses electrolytes to help regulate nerve and muscle function and to maintain acid-base balance (see page 972) and fluid balance.
To function normally, the body must keep fluid levels from varying too much in the areas of the body that contain fluid (called compartments). The three main compartments are
Fluid within cells
Fluid in the space around cells
Blood
Electrolytes, particularly sodium, help the body maintain normal fluid levels in these compartments (called fluid balance), because how much fluid a compartment contains depends on the concentration of electrolytes in it. If the electrolyte concentration is high, fluid moves into that compartment. If the electrolyte concentration is low, fluid moves out of that compartment. To adjust fluid levels, the body can actively move electrolytes in or out of cells. Thus, having electrolytes in the right concentrations (called electrolyte balance) is important in maintaining fluid balance among the compartments.
The kidneys help maintain electrolyte concentrations by filtering electrolytes from blood, returning some electrolytes, and excreting any excess into the urine. Thus, the kidneys help maintain a balance between daily consumption and excretion.
If the balance of electrolytes is disturbed, disorders can develop. An electrolyte imbalance can result from the following:
Becoming dehydrated
Taking certain drugs
Having certain heart, kidney, or liver disorders
Being given intravenous fluids or feedings in inappropriate amounts
Diagnosis
Doctors can detect many common nutritional disorders or an electrolyte imbalance by measuring the levels of minerals in a sample of blood or urine.
Calcium
About 99% of the body’s calcium is stored in the bones, but cells (particularly muscle cells) and blood also contain calcium. Calcium is essential for the following:
Formation of bone and teeth
Muscle contraction
Normal functioning of many enzymes
Blood clotting
Normal heart rhythm
The body precisely controls the amount of calcium in cells and blood. The body moves calcium out of bones into blood as needed to maintain a steady level of calcium in the blood. If people do not consume enough calcium, too much calcium is mobilized from the bones, weakening them. Osteoporosis can result. To maintain a normal level of calcium in blood without weakening the bones, people need to consume at least 1,000 to 1,500 milligrams of calcium a day. The level of calcium in blood is regulated primarily by two hormones: parathyroid hormone and calcitonin.
Parathyroid hormone is produced by the four parathyroid glands, located around the thyroid gland in the neck. When the calcium level in blood decreases, the parathyroid glands produce more parathyroid hormone. When the calcium level in blood increases, the parathyroid glands produce less hormone. Parathyroid hormone does the following:
Stimulates bones to release calcium into blood
Causes the kidneys to excrete less calcium in urine
Stimulates the digestive tract to absorb more calcium
Causes the kidneys to activate vitamin D, which enables the digestive tract to absorb more calcium
Calcitonin is produced by cells of the thyroid gland. It lowers the calcium level in blood by slowing the breakdown of bone, but only slightly.
HYPOCALCEMIA
In hypocalcemia, the calcium level in blood is too low.
A low calcium level may result from a problem with the parathyroid glands, as well as from diet, kidney disorders, or certain drugs.
As hypocalcemia progresses, people may become confused, depressed, and forgetful and have tingling in their fingers and feet as well as stiff, achy muscles.
Usually, the disorder is detected by routine blood tests.
Calcium and vitamin D supplements may be used.
MINERALS
About 40% of the calcium in blood is attached (bound) to proteins in blood, mainly albumin. Protein-bound calcium acts as a reserve but has no active function in the body. Only unbound calcium affects the body’s functions. Thus, hypocalcemia causes problems only when the level of unbound calcium is low. Unbound calcium has an electrical (ionic) charge, so it is called ionized calcium.
Causes
Hypocalcemia most commonly results when too much calcium is lost in urine or when not enough calcium is moved from bones into the blood. Causes of hypocalcemia include the following:
A low level of parathyroid hormone (hypoparathyroidism), as can occur when the parathyroid glands are damaged during thyroid gland surgery
Lack of response to a normal level of parathyroid hormone (pseudohypoparathyroidism)
No parathyroid glands at birth
A low level of magnesium (hypomagnesemia), which reduces the activity of parathyroid hormone
Vitamin D deficiency (due to inadequate consumption or inadequate exposure to sunlight)
Kidney dysfunction (a common cause), which results in more calcium excreted in urine and makes the kidneys less able to activate vitamin D
Inadequate consumption of calcium
Disorders that decrease calcium absorption
Pancreatitis
Certain drugs, including rifampin (an antibiotic), anticonvulsants (such as phenytoin and phenobarbital), bisphosphonates (such as alendronate, ibandronate, risedronate, and zoledronic acid), calcitonin, chloroquine, corticosteroids, and plicamycin
Symptoms
The calcium level in blood can be moderately low without causing any symptoms. Over time, hypocalcemia can affect the brain and cause neurologic or psychologic symptoms, such as confusion, memory loss, delirium, depression, and hallucinations. These symptoms disappear if the calcium level is restored.
An extremely low calcium level may cause tingling (often in the lips, tongue, fingers, and feet), muscle aches, spasms of the muscles in the throat (leading to difficulty breathing), stiffening and spasms of muscles (tetany), seizures, and abnormal heart rhythms.
Diagnosis
Hypocalcemia is often detected by routine blood tests before symptoms become obvious. Doctors measure the total calcium level (which includes calcium bound to albumin) and the albumin level in blood to determine whether the level of unbound calcium is low.
Blood tests are done to evaluate kidney function and to measure magnesium, phosphate, parathyroid hormone, and vitamin D levels. Other substances in blood may be measured to help determine the cause.
Treatment
Calcium supplements, given by mouth, are often all that is needed to treat hypocalcemia. If a cause is identified, treating the disorder causing hypocalcemia or changing drugs may restore the calcium level.
Once symptoms appear, calcium is usually given intravenously. Taking vitamin D supplements helps increase the absorption of calcium from the digestive tract. Thiazide diuretics may be given to decrease the excretion of calcium by the kidneys, particularly when hypocalcemia is caused by hypoparathyroidism.
HYPERCALCEMIA
In hypercalcemia, the level of calcium in blood is too high.
A high calcium level may result from a problem with the parathyroid glands, as well as from diet, cancer, or disorders affecting bone.
At first, people have digestive problems, feel thirsty, and may urinate a lot, but if severe, the disorder can be life threatening.
Usually, the disorder is detected by routine blood tests.
Drinking lots of fluids may be sufficient, but diuretics may increase calcium excretion and drugs can be used to slow the release of calcium from bone if needed.
Causes
Causes include the following:
Hyperparathyroidism: One or more of the four parathyroid glands secrete too much parathyroid hormone, which helps control the amount of calcium in blood.
Too much calcium: Occasionally, hypercalcemia develops in people with peptic ulcers if they drink a lot of milk and take calcium-containing antacids for relief. The resulting disorder is called the milk-alkali syndrome.
Too much vitamin D: If people take very high daily doses of vitamin D over several months, the
amount of calcium absorbed from the digestive tract increases substantially.
Cancer: Cells in kidney, lung, and ovary cancers may secrete large amounts of a protein that, like parathyroid hormone, increases the calcium level in blood. These effects are considered a paraneoplastic syndrome (see box on page 1082). Calcium can also be released into blood when cancer spreads (metastasizes) to bone and destroys bone cells. Such bone destruction occurs most commonly with prostate, breast, and lung cancers. Multiple myeloma (a cancer involving bone marrow) can also lead to the destruction of bone and result in hypercalcemia. Other cancers can increase the calcium level in blood by means not yet fully understood.
Bone disorders: If bone is broken down (resorbed) or destroyed, calcium is released into the blood, sometimes causing hypercalcemia. In Paget’s disease, bone is broken down, but the calcium level in blood is usually normal. However, the calcium level can become too high if people with Paget’s disease become dehydrated or spend too much time sitting or lying down—when the bones are not bearing weight.
Inactivity: Rarely, people who are immobilized, such as paraplegics, quadriplegics, or people who must remain in bed for a long time, develop hypercalcemia because calcium in bone is released into the blood when bones do not bear weight for long periods of time.
Did You Know…
Lack of mobility can make the calcium level high because bones weaken and release calcium into the blood.
Symptoms and Diagnosis
Hypercalcemia often causes no symptoms. The earliest symptoms are usually constipation, nausea, vomiting, abdominal pain, and loss of appetite. People may excrete abnormally large amounts of urine, resulting in dehydration and increased thirst.
Very severe hypercalcemia often causes brain dysfunction with confusion, emotional disturbances, delirium, hallucinations, and coma. Muscle weakness may occur, and abnormal heart rhythms and death can follow. Long-term or severe hypercalcemia commonly results in kidney stones containing calcium. Less commonly, kidney failure develops, but it usually resolves with treatment. However, if enough calcium accumulates within the kidneys, damage is irreversible.
What Is Hyperparathyroidism?
The parathyroid glands release parathyroid hormone, which increases the absorption of calcium from the digestive tract and causes bones to release stored calcium. If the parathyroid glands release too much parathyroid hormone, hyperparathyroidism results. People with hyperparathyroidism have too much calcium and a normal or low level of phosphate in their blood. Parathyroid hormone causes the kidneys to excrete more phosphate, but it also causes the bones to release phosphate into the blood. The balance between these two effects determines whether the phosphate level remains normal or decreases.
Primary hyperparathyroidism: An abnormality causes the release of too much parathyroid hormone. In about 90% of people with primary hyperparathyroidism, the abnormality is a non-cancerous tumor (adenoma) in one of the parathyroid glands. In the remaining 10%, the glands simply enlarge and produce too much hormone. Rarely, cancers of the parathyroid glands cause hyperparathyroidism.
Primary hyperparathyroidism is more common among women than among men. It is more likely to develop in older people and in people who have received radiation therapy to the neck. Sometimes it occurs as part of the syndrome of multiple endocrine neoplasia, a rare hereditary disorder (see page 1016).
Primary hyperparathyroidism is usually treated by surgically removing one or more of the parathyroid glands. The goal is to remove all parathyroid tissue that is producing excess hormone. Surgery is successful in almost 90% of cases.
Secondary hyperparathyroidism: Excess parathyroid hormone is released in response to a large decrease in the calcium level in blood, as can occur in chronic kidney disease and vitamin D deficiency.
Treatment depends on the cause.
Hypercalcemia is usually detected during routine blood tests.
Treatment
If hypercalcemia is not severe, correcting the cause is often sufficient. If people have mild hypercalcemia or conditions that can cause hypercalcemia and if their kidney function is normal, they are usually advised to drink plenty of fluids. Fluids stimulate the kidneys to excrete calcium and help prevent dehydration.
If the calcium level is very high or if symptoms of brain dysfunction or muscle weakness appear, fluids and diuretics are given intravenously as long as kidney function is normal. Dialysis is a highly effective, safe, reliable treatment, but it is usually used only for people with severe hypercalcemia that cannot be treated by other methods.
Several other drugs (including bisphosphonates, calcitonin, corticosteroids, and, rarely, plicamycin) can be used to treat hypercalcemia. These drugs work primarily by slowing the release of calcium from bone.
Hypercalcemia caused by cancer is particularly difficult to treat. If the cancer cannot be controlled, hypercalcemia usually returns despite the best treatment.
Chromium
Chromium enables insulin (which controls blood sugar levels) to function and helps in the processing (metabolism) and storage of carbohydrates, protein, and fat. Only a small amount of the chromium in food is absorbed. Chromium is absorbed better when eaten with foods that contain vitamin C and niacin. Supplements do not enhance muscle size or strength in men.
Deficiency: Chromium deficiency is rare in developed countries. Children who are undernourished may have chromium deficiency and grow poorly. Several conditions can reduce the amount of chromium in the body:
A diet high in simple sugars, which causes more chromium to be excreted in urine
Infections
Exercise if strenuous
Pregnancy and breastfeeding
Injuries
Intravenous feeding (total parenteral nutrition) for a long time.
Symptoms may include weight loss, confusion, impaired coordination, and a reduced response to sugar (glucose) in blood, increasing the risk of diabetes. Treatment may involve chromium supplements.
Excess: Small amounts of chromium taken by mouth are not harmful. In the workplace, people may be exposed to a different, toxic form of chromium. This form results from industrial pollution. This form may irritate the skin, cartilage of the nose, lungs, and digestive tract and may cause lung cancer.
Copper
Most of the copper in the body is located in the liver, bones, and muscle, but traces of copper occur in all tissues of the body. The liver excretes excess copper into the bile for elimination from the body. Copper is a component of many enzymes, including ones that are necessary for the following:
Energy production
Formation of the hormone epinephrine
Formation of red blood cells, bone, or connective tissue (which binds other tissues and organs together)
Antioxidant action (to help protect cells against damage by free radicals, which are reactive by-products of normal cell activity)
WILSON’S DISEASE
In Wilson’s disease, a rare hereditary disorder, the liver does not excrete excess copper into the bile as it normally does, resulting in accumulation of copper in the liver and liver damage.
Copper accumulates in the liver, brain, eyes, and other organs.
People with Wilson’s disease may have tremors, difficulty speaking and swallowing, problems with coordination, personality changes, or hepatitis.
Blood tests and eye examinations help confirm the diagnosis.
People must take drugs to remove copper and must avoid foods high in copper for the rest of their life.
Because the liver does not excrete excess copper, copper accumulates in the liver and damages it, causing cirrhosis. The damaged liver releases copper directly into the blood, and copper is carried to other organs, such as the brain, kidneys, and eyes, where it also accumulates.
Symptoms
Symptoms usually begin between ages 6 and 30. In almost half of affected people, the first symptoms result from brain damage. They include tremors, difficulty speaking and swallowing, drooling, incoordination, involuntary jerky movements (chorea), personality changes, and even psychosis (such as schizophrenia or manic-depressive illness). In most of the other people, the first symptoms result from liver damage, which causes hepatitis and eventually cirrhosis.
The cornea of the eyes may contain outer gold or greenish gold rings (Kayser-Fleischer rings) caused by copper that accumulates there. People may have anemia because red blood cells rupture (causing hemolytic anemia). Women may have no menstrual periods or repeated miscarriages.
Diagnosis
Doctors suspect Wilson’s disease based on symptoms, such as unexplained hepatitis, tremors, and personality changes. The following tests help confirm the diagnosis:
Slit-lamp examination of the eyes for Kayser-Fleischer rings
Blood tests to measure levels of copper and copper proteins
Measurement of copper excreted in the urine
If the diagnosis is still unclear, a liver biopsy
If children have a family history of the disease, tests are done after about age 1 year. Tests done earlier are likely to miss the disease.
Treatment
Drugs that bind with copper, such as penicillamine, taken by mouth, are used to remove the accumulated copper. People also need to follow a diet that is low in copper. Foods to avoid include beef liver, cashews, black-eyed peas, vegetable juice, shellfish, mushrooms, and cocoa. For the rest of their life, people with Wilson’s disease must take penicillamine, another similar drug, or zinc supplements. These drugs help prevent copper from reaccumulating. Without lifelong treatment, Wilson’s disease is fatal.
People who do not take the drugs as directed, especially younger people, may develop liver failure. Liver transplantation can cure the disease.
Did You Know…
Greenish gold rings around the outer rim of the corneas of the eyes may be a sign of Wilson’s disease.
COPPER DEFICIENCY
Copper deficiency is rare among healthy people. It occurs most commonly among infants who are premature, who are recovering from severe undernutrition, or who have persistent diarrhea. A severe disorder that impairs absorption of nutrients (such as celiac disease, Crohn’s disease, cystic fibrosis, or tropical sprue) or weight-loss (bariatric) surgery may cause this deficiency. Consumption of too much zinc can reduce the absorption of copper, causing a deficiency. Some male infants inherit a genetic abnormality that causes copper deficiency. This disorder is called Menkes syndrome.
Symptoms of copper deficiency include fatigue, anemia, and a decreased number of white blood cells. Sometimes osteoporosis develops or nerves are damaged. Nerve damage can cause tingling and loss of sensation in the feet and hands. Muscles may feel weak. Some people become confused, irritable, and mildly depressed. Coordination is impaired.
Menkes syndrome causes severe mental retardation, vomiting, and diarrhea. The skin lacks pigment, and the hair is sparse, steely, or kinky. Bones may be weak and malformed, and arteries are fragile, sometimes rupturing.
Copper deficiency is usually diagnosed based on symptoms and on blood tests that detect low levels of copper and ceruloplasmin (a copper-carrying protein).
The cause is treated, and a copper supplement is given by mouth. For infants with Menkes syndrome, copper is injected under the skin (subcutaneously).
COPPER EXCESS
Consumption of excess copper is rare. People may consume small amounts of excess copper in acidic food or beverages that have been in copper vessels, tubing, or valves a long time. Consuming even relatively small amounts of copper may cause nausea, vomiting, and diarrhea. Large amounts, usually consumed by people intending to commit suicide, can damage the kidneys, inhibit urine production, and cause anemia due to the rupture of red blood cells (hemolytic anemia) and even death. Rarely, liver damage or cirrhosis occurs in children. It probably results from drinking milk that has been boiled or stored in corroded copper or brass vessels.
Doctors measure copper and ceruloplasmin levels in blood or urine. However, a liver biopsy is usually required for diagnosis unless large amounts of copper were consumed.
If large amounts of copper were consumed, the stomach is pumped, and dimercaprol is injected into a muscle. Then drugs that bind with copper, such as penicillamine, are given to remove excess copper. Occasionally, death occurs despite treatment. Children with liver damage are treated with penicillamine.
Fluoride
In the body, most fluoride is contained in bones and teeth. Fluoride is necessary for the formation and health of bones and teeth.
FLUORIDE DEFICIENCY
Fluoride deficiency can lead to tooth decay and possibly osteoporosis. Consuming enough fluoride can prevent tooth decay and may strengthen bones. The addition of fluoride (fluoridation) to drinking water that is low in fluoride or the use of fluoride supplements significantly reduces the risk of tooth decay. In areas where drinking water is not fluoridated, children may be given fluoride by mouth.
FLUORIDE EXCESS
People who live in areas where the drinking water has a naturally high fluoride level may consume too much fluoride—causing a condition called fluorosis. Fluoride accumulates in teeth, particularly permanent teeth. Chalky white, irregular patches appear on the surface of the tooth enamel. The patches become stained yellow or brown, causing the enamel to appear mottled. The teeth may also become pitted. These defects appear to affect appearance only and may even make the enamel more resistant to cavities. Fluoride also accumulates in bones. Rarely, consuming too much fluoride for a long time results in dense but weak bones, abnormal bone growths (spurs) on the spine, and crippling due to calcium accumulation (calcification) in ligaments.
The diagnosis is based on symptoms.
Treatment involves reducing fluoride consumption. For example, if people live in areas with high fluoride levels in the water, they should not drink fluoridated water or take fluoride supplements. Children should always be instructed not to swallow fluoridated toothpaste.
Iodine
The thyroid gland contains most of the iodine in the body. Iodine in the thyroid gland is necessary for the formation of thyroid hormones. Iodine occurs in seawater. A small amount of iodine enters the atmosphere and, through rain, enters ground water and soil near the sea. In many areas, including the United States, table salt is fortified with iodine (in its combination form iodide) to help make sure people consume enough.
IODINE DEFICIENCY
Iodine deficiency is rare in areas where iodine is added to table salt. However, the deficiency is common worldwide. People living far from the sea and at higher altitudes are at particular risk of iodine deficiency because their environment, unlike that near the sea, contains little, if any, iodine.
When iodine is deficient, the thyroid gland enlarges, forming a goiter, as it attempts to capture more iodine for the production of thyroid hormones. The thyroid gland becomes underactive and produces too little thyroid hormones (hypothyroidism —see page 995). The person’s IQ may be decreased. Fertility is reduced. In adults, hypothyroidism may cause puffy skin, a hoarse voice, impaired mental function, dry and scaly skin, sparse and coarse hair, intolerance to cold, and weight gain.
If pregnant women have iodine deficiency, the risk of miscarriage and stillbirth is increased. The fetus may grow slowly, and the brain may develop abnormally. Unless affected babies are treated soon after birth, mental retardation with short stature (cretinism) develops. Babies may have birth defects or hypothyroidism.
Did You Know…
Lack of iodine during pregnancy increases the risk of miscarriage, stillbirth, and mental retardation and birth defects in the baby.
Diagnosis and Treatment
Iodine deficiency is diagnosed based on blood tests indicating low levels of thyroid hormones or a high level of thyroid-stimulating hormone (TSH) or on the presence of a goiter (only in adults). The amount of iodine in urine is measured. The lower the amount, the more severe the deficiency. Imaging tests, such as ultrasonography or thyroid scanning, may be done to measure the thyroid gland and to evaluate any abnormalities.
Treatment consists of iodine supplements, taken by mouth. Infants may also require supplements of thyroid hormone, sometimes throughout life.
IODINE EXCESS
Excess consumption of iodine is uncommon. It usually results from taking iodine supplements to treat a prolonged iodine deficiency. Sometimes people who live near the sea consume too much iodine because they eat a lot of seafood and seaweed and drink water that is high in iodine, as is common in northern Japan.
Consuming too much usually does not affect thyroid function, but sometimes does. It may cause the thyroid gland to become overactive and produce excess thyroid hormones (hyperthyroidism—see page 992). As a result, the thyroid gland enlarges, forming a goiter. (Goiters can also form when the thyroid gland is underactive.) If people consume very large amounts of iodine, they may have a brassy taste in their mouth and produce more saliva. Iodine can irritate the digestive tract and cause a rash.
Consuming too much iodine may also make the thyroid gland become underactive (hypothyroidism), especially if the thyroid gland had been underactive previously (for example, in people with Hashimoto’s thyroiditis—see page 996).
Diagnosis and Treatment
Doctors suspect hyperthyroidism or hypothyroidism due to excess iodine based on symptoms, particularly in people who report taking iodine supplements, who live near the sea, or who consume a lot of seaweed or seafood. Blood tests to determine levels of thyroid hormones and thyroid-stimulating hormone (TSH) are done. Imaging tests may also be done.
People are advised to use salt that is not fortified with iodine and to reduce their consumption of foods that contain iodine. If people have hypothyroidism due to consuming too much iodine, consuming less iodine often cures the disorder, but some people must take thyroid hormones for the rest of their life.
Iron
Much of the iron in the body is contained in hemoglobin. Hemoglobin is the component of red blood cells that enables them to carry oxygen and deliver it to the body’s tissues. Iron also is an important component of muscle cells. It is also necessary for the formation of many enzymes in the body.
The body recycles iron: When red blood cells die, the iron in them is returned to the bone marrow to be used again in new red blood cells. A small amount of iron is lost each day, mainly in cells shed from the lining of the intestine. This amount is usually replaced by the 1 to 2 milligrams of iron absorbed from food each day.
Food contains two types of iron:
Heme iron: Animal products contain heme iron. It is absorbed much better than nonheme iron.
Nonheme iron: Most foods and iron supplements contain nonheme iron. It accounts for more than 85% of iron in the average diet. However, less than 20% of nonheme iron that is consumed is absorbed into the body. Nonheme iron is absorbed better when it is consumed with animal protein and with vitamin C.
IRON DEFICIENCY
Iron deficiency usually results from loss of blood in adults but, in children and pregnant women, may result from an inadequate diet.
Anemia develops, making people appear pale and feel weak and tired.
Doctors base the diagnosis on symptoms and blood test results.
Doctors look for a source of bleeding, and if one is identified, they treat it.
Iron supplements, usually taken by mouth, are often needed.
Iron deficiency is one of the most common mineral deficiencies in the world. It causes anemia in men, women, and children.
In adults, iron deficiency is most commonly caused by loss of blood. In premenopausal women, monthly menstrual bleeding may cause the deficiency. In men and postmenopausal women, iron deficiency usually indicates bleeding, most often in the digestive tract—for example, from a bleeding ulcer or a polyp in the colon. Chronic bleeding due to colon cancer is a serious cause in middle-aged and older people.
Iron deficiency may result from an inadequate diet, primarily in infants and small children, who need more iron because they are growing. Adolescent girls who do not eat meat are at risk of developing iron deficiency because they are growing and starting to menstruate. Pregnant women are at risk of this deficiency because the growing fetus requires large amounts of iron.
Symptoms
When iron reserves in the body are exhausted, anemia develops (see page 1035). Anemia causes paleness, weakness, and fatigue. People usually do not notice how pale they are because it happens so gradually. Concentration and learning ability may be impaired. When severe, anemia may cause shortness of breath, dizziness, and a rapid heart rate. Occasionally, severe anemia causes chest pain and heart failure. Menstrual periods may stop.
In addition to anemia, iron deficiency may cause pica (a craving for nonfoods such as ice, dirt, or pure starch), spoon nails (thin, concave fingernails), and leg cramps at night. Rarely, iron deficiency causes a thin membrane to grow across part of the esophagus, making swallowing difficult.
Diagnosis
Iron deficiency is diagnosed based on symptoms and blood test results. Results include a low level of hemoglobin (which contains iron), a low hematocrit (the percentage of blood volume that is red blood cells), a low number of red blood cells, and the presence of abnormally small red blood cells. Blood tests also include the following:
Transferrin: Transferrin is the protein that carries iron in blood when iron is not inside red blood cells. If the percentage of iron in transferrin is less than 10%, iron deficiency is likely.
Ferritin: Ferritin is a protein that stores iron. Iron deficiency is confirmed if the ferritin level is low.
However, the ferritin level may be normal or high when iron deficiency is present if people have inflammation, an infection, cancer, or liver damage.
Occasionally, a bone marrow examination is needed to make the diagnosis. A sample of bone marrow cells is removed, usually from the hipbone, through a needle and examined under a microscope to determine the iron content.
Treatment
Because the most common cause of iron deficiency in adults is excessive bleeding, doctors first look for a source of bleeding. If the source is excessive menstrual bleeding, drugs, such as oral contraceptives (birth control pills), may be needed to control it. Surgery may be needed to repair a bleeding ulcer or remove a polyp in the colon. A blood transfusion may be necessary if the anemia is severe.
Normal dietary intake of iron may not be sufficient to replace lost iron (because less than 20% of iron in a typical diet is absorbed into the body). Thus, most people with iron deficiency need to take iron supplements by mouth usually once or twice a day. Iron in supplements is absorbed best when taken on an empty stomach, 30 minutes before meals or 2 hours after meals, particularly if the meals include foods that reduce the absorption of iron (such as vegetable fibers, phytates, bran, coffee, and tea). However, taking iron supplements on an empty stomach can cause indigestion and constipation. So some people must take the supplements with meals. Antacids and calcium supplements can also reduce iron absorption. Consuming vitamin C in juices or taking it as a supplement enhances iron absorption, as does eating small amounts of meat, which contains the more easily absorbed form of iron (heme iron). Iron supplements almost always turn stools black—a harmless side effect.
Rarely, iron is given by injection. Injections are necessary for people who cannot tolerate tablets or for a few people who cannot absorb enough iron from the digestive tract.
Correcting iron deficiency anemia usually takes 3 to 6 weeks, even after the bleeding has stopped. After the anemia is corrected, an iron supplement should be taken for 6 months to replenish the body’s reserves. Blood tests are usually done periodically to determine whether people are receiving enough iron and to check for continued bleeding.
Women who are not menstruating and men should not take iron supplements or multiple vitamins with iron unless they are specifically instructed to do so by a doctor. Taking such supplements can make diagnosing bleeding from the intestine difficult. Such bleeding may be due to serious disorders, including colon cancer.
Because a developing fetus requires iron, iron supplements are recommended for most pregnant women. Most babies, particularly those who are premature or who have a low birth weight, need an iron supplement. It is given as an iron-fortified formula or, to breastfed babies, as a separate liquid supplement.
IRON EXCESS
Excess iron can accumulate in the body. Causes include the following:
Repeated blood transfusions
Iron therapy given in excessive amounts or for too long
Chronic alcoholism
An overdose of iron
A hereditary disorder called hemochromatosis
Excess iron consumed all at once causes vomiting, diarrhea, and damage to the intestine and other organs. Excess iron consumed over a period of time may damage coronary arteries.
Often, deferoxamine is given intravenously. This drug binds with iron and carries it out of the body in urine. Hemachromatosis is treated with bloodletting (phlebotomy).
HEMOCHROMATOSIS
In hemochromatosis, a hereditary disorder, too much iron is absorbed, resulting in the accumulation of iron in the body.
Iron can accumulate and damage any part of the body.
People may develop symptoms of cirrhosis or diabetes or simply feel tired.
Blood tests identify people who require genetic testing, which can confirm the disorder.
Bloodletting, done periodically, can prevent further damage.
In the United States, over 1 million people have hemochromatosis. The disorder is potentially fatal but usually treatable. The gene associated with hemochromatosis has been identified.
Symptoms
Usually, symptoms develop gradually, often not appearing until middle age or later. In women, symptoms usually start after menopause because the loss of iron during menstrual bleeding and the increased requirement for iron during pregnancy compensate to some degree.
Symptoms vary because iron accumulation can damage any part of the body, including the brain, liver, pancreas, lungs, or heart. The first symptoms, particularly in men, may be those of cirrhosis (due to liver damage) or those of diabetes (due to pancreas damage). Or, the first symptoms, particularly in women, may be vague and affect the whole body. Fatigue is an example. Liver dysfunction is the most common problem. The following problems can also occur:
Bronze-colored skin
Heart failure (occasionally)
Joint pains
Increased risk of liver cancer
Infertility
An underactive thyroid gland (hypothyroidism)
Chronic fatigue
In many men, levels of male hormones decrease. Erectile dysfunction (impotence) may occur. Hemochromatosis can worsen neurologic disorders that are already present.
Diagnosis
Identifying hemochromatosis based on symptoms may be difficult. However, blood tests to measure the levels of iron and two other substances can identify people who should be further evaluated. These substances are ferritin, a protein that stores iron, and the iron in transferrin, the protein that carries iron in blood when iron is not inside red blood cells. If the ferritin level and percentage of iron in transferrin are high, genetic testing is usually done to confirm the diagnosis. A liver biopsy may be necessary to determine whether the liver has been damaged.
Genetic testing is recommended for people with hemochromatosis and all of their first-degree relatives (siblings, parents, and children).
Treatment
Usually, bloodletting (phlebotomy) is the best treatment. It prevents additional organ damage but does not reverse existing damage. Bloodletting is done once or sometimes twice a week. Each time, about 500 milliliters (1 pint) of blood is removed until the iron level and percentage of iron in transferrin are normal. Bloodletting is then done periodically to keep these substances at normal levels.
With early diagnosis and treatment of hemochromatosis, a long, healthy life is possible.
Magnesium
Bone contains most of the body’s magnesium. Blood contains very little. Magnesium is necessary for the formation of bone and teeth and for normal nerve and muscle function. Many enzymes in the body depend on magnesium to function normally. The body obtains magnesium from foods and excretes it in urine and stool.
HYPOMAGNESEMIA
In hypomagnesemia, the level of magnesium in blood is too low.
Usually, the level becomes low because people consume less (most often, because of starvation) or because the intestine cannot absorb nutrients normally (called malabsorption). But sometimes hypomagnesemia develops because the kidneys or intestine excrete too much magnesium. Hypomagnesemia may result from the following:
Consuming large amounts of alcohol (common), which reduces consumption of food (and thus magnesium) and increases excretion of magnesium
Protracted diarrhea (common), which increases excretion
High levels of aldosterone, antidiuretic hormone, or thyroid hormones, which increase excretion
Drugs that increase excretion, including diuretics, the antifungal drug amphotericin B, and the chemotherapy drug cisplatin
Breastfeeding, which increases requirements for magnesium
Hypomagnesemia may cause nausea, vomiting, sleepiness, weakness, personality changes, muscle spasms, tremors, and loss of appetite. If severe, hypomagnesemia can cause seizures, especially in children.
The diagnosis is usually based on blood tests indicating that the magnesium level is low.
Magnesium is given by mouth when the deficiency causes symptoms or persists. All alcoholics are given magnesium. If a very low magnesium level is causing severe symptoms or if people cannot take magnesium by mouth, magnesium is given by injection into a muscle or vein.
HYPERMAGNESEMIA
In hypermagnesemia, the level of magnesium in blood is too high.
Hypermagnesemia usually develops only when people with kidney failure are given magnesium salts or take drugs that contain magnesium (such as some antacids or laxatives).
Hypermagnesemia may cause weakness, low blood pressure, and impaired breathing. When hypermagnesemia is severe, the heart can stop beating.
The diagnosis is based on blood tests indicating that the magnesium level is high.
People with severe hypermagnesemia are given calcium gluconate intravenously. Diuretics (particularly if given intravenously) can increase the kidneys’ excretion of magnesium. However, if the kidneys are not functioning well (as is typical) or if hypermagnesemia is severe, dialysis is usually needed.
Molybdenum
Molybdenum is required for processing (metabolizing) nitrogen, activating certain enzymes, and enabling cells to function normally. Molybdenum also helps break down sulfites (which occur in foods naturally and are added as preservatives).
Molybdenum deficiency is rare. It may result from genetic disorders or inadequate consumption. Symptoms seem to vary. They may include mental retardation, seizures, increased heart and breathing rates, headache, nausea, vomiting, and coma.
Molybdenum excess is even more rare. It may cause swollen, painful joints and abnormalities of the digestive tract, liver, and kidneys.
Phosphate
In the body, almost all phosphorus is combined with oxygen, forming phosphate. Bone contains about 85% of the body’s phosphate. The rest is located primarily inside cells, where it is involved in energy production.
Phosphate is necessary for the formation of bone and teeth. Phosphate is also used as a building block for several important substances, including those used by the cell for energy, cell membranes, and DNA (deoxyribonucleic acid). The body obtains phosphate from foods and excretes it in urine and stool.
HYPOPHOSPHATEMIA
In hypophosphatemia, the level of phosphate in blood is too low.
The phosphate level in blood may become low over time, resulting in chronic hypophosphatemia. Chronic hypophosphatemia usually develops because too much phosphate is excreted. Causes include the following:
Hyperparathyroidism
Chronic diarrhea
Impaired kidney function or hemodialysis
An underactive thyroid gland (hypothyroidism)
Use of diuretics for a long time
Use of large amounts of aluminum-containing antacids for a long time
Use of large amounts of theophylline (used to treat asthma)
The phosphate level in blood can suddenly fall dangerously low in people recovering from the following conditions because the body uses large amounts of phosphate during recovery:
Severe undernutrition (including starvation)
Diabetic ketoacidosis
Severe alcoholism
Severe burns
This may result in an irregular heart rhythm and even death.
Did You Know…
Some people who survived concentration camps died because their already low phosphate level suddenly fell when they began eating a normal diet, a phenomenon called refeeding syndrome.
Symptoms occur only when the phosphate level in blood becomes very low. Muscle weakness develops, followed by stupor, coma, and death. In mild chronic hypophosphatemia, the bones can weaken, resulting in bone pain and fractures. People may become weak and lose their appetite.
Diagnosis and Treatment
The diagnosis is based on blood tests indicating that the phosphate level is low. Doctors do other tests to identify the cause if it is not readily apparent.
Any drugs that can reduce the phosphate level are stopped. If hypophosphatemia is mild and causes no symptoms, drinking low-fat or skim milk, which provides a large amount of phosphate, may help. Or people can take phosphate by mouth, but doing so usually causes diarrhea. If hypophosphatemia is very severe or if phosphate cannot be taken by mouth, phosphate may be given intravenously.
HYPERPHOSPHATEMIA
In hyperphosphatemia, the level of phosphate in blood is too high.
Hyperphosphatemia is rare except in people with severe kidney dysfunction. In these people, the kidneys do not excrete enough phosphate. Dialysis, often used to treat them, is not very effective at removing phosphate and thus does not reduce the risk of hyperphosphatemia.
Less commonly, hyperphosphatemia develops in people with the following:
A low level of parathyroid hormone (hypoparathyroidism)
Lack of response to a normal level of parathyroid hormone (pseudohypoparathyroidism)
Diabetic ketoacidosis
Crush injuries
Destruction of muscle tissue (rhabdomyolysis)
Severe bodywide infections
Large amounts of phosphate taken by mouth or given in an enema
Most people with hyperphosphatemia do not have symptoms. However, in people with severe kidney dysfunction, calcium combines with phosphate to form crystals (calcify) in the walls of the blood vessels and heart. Severe arteriosclerosis (hardening of the arteries) can result, leading to strokes, heart attacks, and poor circulation. Crystals can also form in the skin, where they cause severe itching.
Diagnosis and Treatment
The diagnosis is based on blood tests indicating that the phosphate level is high.
Hyperphosphatemia in people with kidney dysfunction is treated by reducing consumption of phosphate and reducing absorption of phosphate from the digestive tract. Foods that are high in phosphate should be avoided. Drugs that bind with phosphate, such as sevelamer and calcium compounds, should be taken with meals as prescribed by a doctor. By binding with phosphate, these drugs make it harder to absorb, and more phosphate is excreted. Sevelamer is often used for people undergoing dialysis because calcium compounds can make calcium-phosphate crystals more likely to form in tissues.
Potassium
Most of the body’s potassium is located inside the cells. Potassium is necessary for the normal functioning of cells, nerves, and muscles.
The body must maintain the potassium level in blood within a narrow range. A potassium level that is too high or too low can have serious consequences, such as an abnormal heart rhythm or even stopping of the heart (cardiac arrest). The body can use the potassium stored within cells to help maintain a constant level of potassium in blood.
The body maintains the right level of potassium by matching the amount of potassium consumed with the amount lost. Potassium is consumed in food and drinks that contain electrolytes (including potassium) and lost primarily in urine. Some potassium is also lost through the digestive tract and in sweat. Healthy kidneys can adjust the excretion of potassium to match changes in consumption.
Some drugs and certain conditions affect the movement of potassium into and out of cells, which greatly influences the potassium level in blood.
HYPOKALEMIA
In hypokalemia, the level of potassium in blood is too low.
A low potassium level has many causes but usually results from vomiting, diarrhea, adrenal gland disorders, or use of diuretics.
A low potassium level can make muscles feel weak, cramp, twitch, or even become paralyzed, and abnormal heart rhythms may develop.
The diagnosis is based on blood tests to measure the potassium level.
Usually, eating foods rich in potassium or taking potassium supplements by mouth is all that is needed.
Typically, the potassium level becomes low because too much is lost from the digestive tract. Sometimes too much potassium is excreted in urine, usually because of diuretics that cause the kidneys to excrete excess sodium, water, and potassium. In many adrenal disorders, such as Cushing’s syndrome (see page 1001), the adrenal glands produce too much aldosterone, a hormone that causes the kidneys to excrete large amounts of potassium.
Certain drugs cause more potassium to move from blood into cells and can result in hypokalemia. However, these drugs usually cause temporary hypokalemia, unless another condition is also causing potassium to be lost.
Hypokalemia is rarely caused by consuming too little because many foods contain potassium.
WHAT MAKES THE POTASSIUM LEVEL DECREASE?
| CAUSE | DISORDERS | DRUGS OR OTHER CIRCUMSTANCES |
| Increased loss from the digestive tract (most common) | Vomiting Diarrhea |
Laxatives if used a long time |
| Increased excretion in urine | Cushing’s syndrome Aldosteronism due to a tumor in the adrenal glands A low level of magnesium (hypomagnesemia) Gitelman’s syndrome Liddle syndrome Bartter syndrome Fanconi syndrome |
Diuretics (commonly) Licorice (natural) if consumed in large amounts Tobacco chewing (certain types) |
| Increased movement from blood into cells | An overactive thyroid gland (hyperthyroidism) | Insulin Some drugs used to treat asthma: albuterol, terbutaline, and theophylline |
| Increased consumption | — | A diet containing potassium-rich foods Potassium supplements Intravenous treatments that contain potassium, such as total parenteral nutrition and blood transfusions |
| Decreased excretion in urine | Kidney failure | Aliskiren Angiotensin-converting enzyme (ACE) inhibitors Angiotensin-receptor blockers Cyclosporine (used to prevent rejection of organ transplants) Diuretics that help the kidneys conserve potassium, such as eplerenone, spironolactone, and triamterene Nonsteroidal anti-inflammatory drugs Tacrolimus (used to prevent rejection of organ transplants) |
| Release of potassium from cells | Burns if severe Crush injuries (involving the destruction of large amounts of muscle tissue) Diabetes Metabolic acidosis |
Cancer chemotherapy Crack cocaine overdose Exercise if strenuous and prolonged |
Symptoms and Diagnosis
A slight decrease in the potassium level in blood usually causes no symptoms. A larger decrease can cause muscle weakness, cramping, twitches, and even paralysis. Abnormal heart rhythms may develop. They may develop even when the decrease is slight if people already have a heart disorder or take the heart drug digoxin.
The diagnosis is made by measuring the potassium level in the blood. Doctors then try to identify what is causing the decrease. The cause may be clear based on the person’s symptoms (such as vomiting) or use of drugs or other substances. If the cause is not clear, doctors measure how much potassium is excreted in urine to determine whether excess excretion is the cause.
Treatment
If a disorder is causing hypokalemia, it is treated.
Usually, potassium can be replaced by eating potassium-rich foods or by taking potassium supplements by mouth. Because potassium can irritate the digestive tract, supplements should be taken in small doses with food several times a day rather than in a single large dose. Special types of potassium supplements, such as wax-impregnated or microencapsulated potassium chloride, are much less likely to irritate the digestive tract.
Potassium is given intravenously in the following situations:
The potassium level is dangerously low.
Supplements taken by mouth are ineffective.
People continue to lose too much potassium to be replaced using supplements taken by mouth.
The low level causes abnormal heart rhythms.
Most people who take diuretics do not need to take potassium supplements. Nevertheless, doctors periodically check the potassium level in blood so that the drug regimen can be changed if necessary. Alternatively, diuretics that help the kidneys conserve potassium (potassium-sparing diuretics), such as amiloride, eplerenone, spironolactone, or triamterene can be used, but only if the kidneys are functioning normally.
HYPERKALEMIA
In hyperkalemia, the level of potassium in blood is too high.
A high potassium level has many causes, including kidney disorders, drugs that affect kidney function, and consumption of too much supplemental potassium.
Usually, hyperkalemia must be severe before it causes symptoms, mainly abnormal heart rhythms.
Doctors usually detect hyperkalemia when blood tests or electrocardiography is done for other reasons.
Treatment includes reducing consumption of potassium, stopping drugs that may cause hyperkalemia, and using drugs to increase potassium excretion.
Usually, hyperkalemia results from several simultaneous problems, including the following:
Kidney disorders (such as kidney failure) that prevent the kidneys from excreting enough potassium
Drugs that prevent the kidneys from excreting normal amounts of potassium (a common cause of mild hyperkalemia)
A diet high in potassium
Treatments that contain potassium
The most common cause of mild hyperkalemia is the use of drugs that decrease blood flow to the kidneys or prevent the kidneys from excreting normal amounts of potassium. Kidney failure can cause severe hyperkalemia on its own. Addison’s disease can also cause hyperkalemia.
Hyperkalemia can develop after a large amount of potassium is released from the cells. The rapid movement of potassium from cells into blood can overwhelm the kidneys and result in life-threatening hyperkalemia.
Symptoms and Diagnosis
Mild hyperkalemia causes few, if any, symptoms. When hyperkalemia becomes more severe, it can cause abnormal heart rhythms. If the level is very high, the heart can stop beating.
Usually, hyperkalemia is first detected when routine blood tests are done or when a doctor notices certain changes on an electrocardiogram. To identify the cause, doctors determine which drugs people are taking and do blood tests to check kidney function.
Treatment
For mild hyperkalemia, reducing consumption of potassium or stopping drugs that prevent the kidneys from excreting potassium may be all that is needed. If the kidneys are functioning, a diuretic may be given to increase potassium excretion. If needed, a resin that absorbs potassium from the digestive tract and passes out of the body in the stool can be given by mouth or enema.
For moderate to severe hyperkalemia, the potassium level must be reduced immediately. Calcium is given intravenously to protect the heart but does not lower the potassium level. Then insulin and glucose are given. They move potassium from blood into cells, thus lowering the potassium level in blood. Albuterol (used mainly to treat asthma) may be given to help lower the potassium level. It is inhaled.
If these measures do not work or if people have kidney failure, dialysis may be necessary to remove the excess potassium.
Selenium
Selenium occurs in all tissues. Selenium works with vitamin E as an antioxidant. It helps protect cells against damage by free radicals, which are reactive by-products of normal cell activity. Selenium may help protect against some cancers. Selenium is also necessary for the thyroid gland to function normally.
SELENIUM DEFICIENCY
Selenium deficiency is rare, even in New Zealand and Finland, where selenium intake is much lower than in the United States and Canada. In certain areas of China, where selenium intake is even lower, people with selenium deficiency are more likely to develop Keshan disease, a viral disease that affects mainly children and young women. Keshan disease damages the walls of the heart, resulting in cardiomyopathy.
In selenium deficiency, antioxidants are lacking in the heart and muscles. As a result, cardiomyopathy and muscle weakness may occur.
Doctors suspect selenium deficiency based on the person’s circumstances and symptoms. Treatment with a selenium supplement may result in a complete recovery. Taking selenium supplements can prevent but not cure cardiomyopathy due to Keshan disease.
SELENIUM EXCESS
Taking more than 1 milligram of a nonprescription selenium supplement each day can have harmful effects. Symptoms include nausea, vomiting, diarrhea, hair loss, abnormal nails, a rash, fatigue, and nerve damage. The breath may smell like garlic.
The diagnosis is based on symptoms, particularly rapid hair loss. Treatment involves reducing selenium consumption.
Sodium
Most of the body’s sodium is located in blood and in the fluid around cells. Sodium helps the body keep fluids in a normal balance (see page 969). Sodium plays a key role in normal nerve and muscle function.
The body obtains sodium through food and drink and loses it primarily in sweat and urine. Healthy kidneys maintain a consistent level of sodium in the body by adjusting the amount excreted in the urine. When sodium consumption and loss are not in balance, the total amount of sodium in the body is affected.
Controlling Blood Volume: The total amount of sodium affects the amount of fluid in blood and around cells. The body continually monitors blood volume and sodium (and other electrolyte) concentrations. When either becomes too high, sensors in the heart, blood vessels, and kidneys detect the increases and stimulate the kidneys to increase sodium excretion, thus returning blood volume to normal. When blood volume or sodium concentration becomes too low, those sensors trigger mechanisms to increase blood volume. These mechanisms include the following:
The kidneys stimulate the adrenal glands to secrete the hormone aldosterone. Aldosterone causes the kidneys to retain sodium and to excrete potassium. When sodium is retained, less urine is produced, eventually causing blood volume to increase.
The pituitary gland secretes antidiuretic hormone. Antidiuretic hormone causes the kidneys to conserve fluid. Then blood volume increases.
HYPONATREMIA
In hyponatremia, the level of sodium in blood is too low.
A low sodium level has many causes, including consumption of too many fluids, kidney failure, heart failure, cirrhosis, and use of diuretics.
At first, people become sluggish and confused, and if hyponatremia worsens, they may have muscle twitches and seizures and become progressively unresponsive.
The diagnosis is based on blood tests to measure the sodium level.
Restricting fluids and stopping use of diuretics can help, but severe hyponatremia is an emergency requiring use of drugs, intravenous fluids, or both.
Causes
Hyponatremia occurs when the body contains too little sodium for the amount of fluid it contains. The body may have too much, too little, or about a normal amount of fluid. In all cases, however, sodium is diluted. For example, people with severe vomiting or diarrhea lose sodium. If they replace their fluid losses with water, sodium is diluted. Disorders, such as cirrhosis and heart failure, can cause the body to retain sodium and fluid. Often the body retains more fluid than sodium, which means the sodium is diluted.
Symptoms
The brain is particularly sensitive to changes in the sodium level in blood. Therefore, symptoms of brain dysfunction, such as sluggishness (lethargy) and confusion, occur first. If the sodium level in blood falls quickly, symptoms tend to develop rapidly and be more severe. Older people are more likely to have severe symptoms.
As hyponatremia becomes more severe, muscle twitching and seizures may occur. People may become unresponsive, aroused only by vigorous stimulation (stupor), and eventually cannot be aroused (coma). Death may follow.
Causes of Hyponatremia
Addison’s disease (underactive adrenal glands)
Blockage of the small intestine
Burns if severe
Cirrhosis (formation of scar tissue in the liver)
Consumption of too much water, as occurs in some psychiatric disorders
Diarrhea
Drugs such as barbiturates, carbamazepine, chlorpropamide, clofibrate, diuretics (most common), opioids, tolbutamide, and vincristine
Heart failure
Hypothyroidism
Kidney disorders
Pancreatitis
Peritonitis (inflammation of the abdominal cavity)
Syndrome of inappropriate secretion of antidiuretic hormone [SIADH]
Vomiting
Diagnosis and Treatment
Hyponatremia is diagnosed by measuring the sodium level in blood. Determining the cause is more complex. Doctors consider the person’s circumstances, including other disorders present and drugs taken. Blood and urine tests are done to evaluate the amount of fluid in the body, the concentration of blood, and content of urine.
Mild hyponatremia can be treated by restricting fluid intake to less than 1 quart per day. If a diuretic is the cause, it is reduced or stopped. If the cause is a disorder, it is treated. Occasionally, people are given a sodium solution intravenously, a diuretic to increase excretion of fluid, or both, usually slowly, over several days. These treatments can correct the sodium level.
Severe hyponatremia is an emergency. To treat it, doctors slowly increase the level of sodium in blood with drugs, intravenous fluids, or sometimes both. Increasing the level too rapidly can result in severe and often permanent brain damage.
SYNDROME OF INAPPROPRIATE SECRETION OF ANTIDIURETIC HORMONE
Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) develops when too much antidiuretic hormone is released by the pituitary gland, causing the body to retain fluid and lower the sodium level by dilution.
Antidiuretic hormone (also called vasopressin) helps regulate the amount of water in the body by controlling how much water is excreted by the kidneys. High levels of antidiuretic hormone decrease water excretion by the kidneys. The pituitary gland produces and releases antidiuretic hormone when the blood volume or blood pressure goes down or when levels of electrolytes (such as sodium) become too high.
Pain, stress, exercise, a low blood sugar level, and certain disorders of the heart, thyroid gland, kidneys, or adrenal glands can stimulate the release of antidiuretic hormone from the pituitary gland, as can the following drugs:
Chlorpropamide (which lowers the blood sugar level)
Carbamazepine (an anticonvulsant)
Vincristine (a chemotherapy drug)
Clofibrate (which lowers cholesterol levels)
Antipsychotic drugs
Aspirin, ibuprofen, and many other nonprescription pain relievers (analgesics)
Vasopressin (synthetic antidiuretic hormone) and oxytocin (both drugs help the body conserve fluids)
Secretion of antidiuretic hormone is termed inappropriate if it occurs even though blood volume and blood pressure are normal or high, electrolyte concentrations are low, and other triggers of antidiuretic hormone release are not present. When antidiuretic hormone is released in these situations, the sodium level in blood decreases, and the body retains too much fluid.
SIADH is common among older people and is fairly common among people who are hospitalized.
Many conditions increase the risk of developing SIADH. SIADH may result when antidiuretic hormone is produced outside the pituitary gland, as occurs in some lung and other cancers.
Symptoms of SIADH tend to be those of the low sodium level in blood (hyponatremia) that accompanies it (see page 948).
Diagnosis and Treatment
Doctors suspect SIADH based on a person’s circumstances and symptoms. Blood and urine tests are done to measure the sodium and potassium levels and to determine how concentrated the blood and urine are (osmolality). Doctors also rule out other possible causes of excess antidiuretic hormone (such as pain, stress, drugs, or cancer). Once SIADH is diagnosed, doctors try to identify the cause and determine how well the pituitary gland is functioning.
WHAT CAUSES SIADH?
| TYPE OF DISORDER | EXAMPLES |
| Brain or nervous system | Abscesses in the brain Bleeding (hemorrhage) within the layers of tissue covering the brain Encephalitis (inflammation of the brain) Guillain-Barre syndrome Head injury Hypothalamus disorders, including tumors (rare) Meningitis Strokes Tumors |
| Lung | Acute respiratory failure Pneumonia Tuberculosis |
| Cancers | Brain cancer Lung cancer Lymphoma Pancreatic cancer Cancer of the small intestine |
| Other | Surgery Undernutrition |
| SIADH = syndrome of inappropriate secretion of antidiuretic hormone. | |
Doctors restrict fluid intake and treat the cause if possible. If the sodium level in blood continues to decrease or does not increase despite restriction of fluid intake, drugs that decrease the effect of antidiuretic hormone on the kidneys (such as demeclocycline or thiazide diuretics) may be used.
HYPERNATREMIA
In hypernatremia, the level of sodium in blood is too high.
Hypernatremia has many causes, but dehydration is most common, including not drinking enough fluids, diarrhea, kidney dysfunction, and diuretics.
Mainly, people are thirsty, and they may become confused or have muscles twitches and seizures.
Blood tests are done to measure the sodium level.
Usually, fluids are given intravenously to slowly reduce the sodium level in the blood.
In hypernatremia, the body contains too little water for the amount of sodium. The sodium level in blood becomes abnormally high when water loss exceeds sodium loss, as typically occurs in dehydration.
SPOTLIGHT ON AGING
As people age, the body is less able to balance fluid and sodium for several reasons:
Decreased thirst: As people age, they sense thirst less quickly or less intensely and thus may not drink fluids when needed.
Changes in the kidneys: The kidneys may function less well. As a result, more fluid may be excreted in urine, and the kidneys may become less able to concentrate urine.
Less fluid in the body: The older body contains less fluid. Only 45% of body weight is fluid in healthy older people, compared with 60% in younger people. This change means that a slight loss of fluid and sodium, as can result from a fever or even breathing rapidly, can have more serious consequences.
Inability to obtain water: Some older people have physical problems that prevent them from getting something to drink when they want or need it. Others may have dementia, which may prevent them from realizing they are thirsty or from saying so. These people may have to depend on other people to provide them with water.
In older people, a low sodium level in blood (hyponatremia) usually results from retaining too much water, as occurs in heart failure. Older people who are given fluids intravenously during hospitalization or before surgery are at high risk of developing hyponatremia. Using liquid nutritional supplements, which are often low in sodium, is another cause of hyponatremia in older people.
A high sodium level in blood (hypernatremia), which is common among older people, usually results from dehydration, which is typically caused by loss of fluid, not consuming enough fluid, or both.
Disorders that increase the risk of sodium-fluid imbalance, such as heart failure and kidney disorders, are common among older people.
Taking a diuretic (which forces the kidneys to excrete more water) increases the risk of hypernatremia further—especially when the weather is hot or when older people become ill and do not drink enough water. Taking a certain type of diuretic (thiazide diuretics, such as hydrochlorothiazide), particularly if the kidneys are not functioning normally, can result in a dangerously low sodium level. Severe symptoms can develop within a few weeks after the drug is started.
Symptoms of hyponatremia or hypernatremia are usually more severe in older people. For example, hyponatremia can result in delirium, causing confusion, agitation, or lethargy.
Usually, hypernatremia results from dehydration (see page 970). For example, people may lose body fluids and become dehydrated from drinking too little, vomiting, diarrhea, diuretic use, or excessive sweating. People with diabetes mellitus and high blood sugar may have excessive urine volumes, causing dehydration. Diabetes insipidus (which causes excessive urine volume without high blood sugar—see page 986) and kidney disorders can also cause dehydration. Rarely adrenal gland disorders can cause hyponatremia without dehydration. Hypernatremia is most common among older people.
Hypernatremia typically causes thirst. The most serious symptoms of hypernatremia result from brain dysfunction. Severe hypernatremia can lead to confusion, muscle twitching, seizures, coma, and death.
Diagnosis and Treatment
The diagnosis is based on blood tests indicating that the sodium level is high.
Hypernatremia is treated by replacing fluids. In all but the mildest cases, dilute fluids (containing water and a small amount of sodium in carefully adjusted concentrations) are given intravenously. The sodium level in blood is reduced very slowly because reducing the level too rapidly can cause permanent brain damage.
Zinc
Zinc is widely distributed in the body—in bones, teeth, hair, skin, liver, muscle, white blood cells, and testes. It is a component of more than 100 enzymes, including those involved in the formation of RNA (ribonucleic acid) and DNA (deoxyribonucleic acid).
The level of zinc in the body depends on the amount of zinc consumed in the diet. Zinc is necessary for healthy skin, healing of wounds, and growth. Much of the zinc consumed in the diet is not absorbed.
ZINC DEFICIENCY
Zinc deficiency has many causes, including diet, various disorders, alcoholism, and diuretics.
People lose their appetite and hair and may feel sluggish and irritable.
Measuring the zinc level in blood is available but is not a good test for zinc status.
Zinc supplements taken by mouth can cure the deficiency.
Many conditions can increase the risk of developing zinc deficiency.
In acrodermatitis enteropathica, a rare hereditary disorder, zinc cannot be absorbed. This disorder may result in diarrhea, hair loss, and zinc deficiency.
Symptoms
Early symptoms include a loss of appetite and, in infants and children, slowed growth and development. People may lose their hair in patches. They may feel sluggish and irritable. Taste and smell may be impaired. Rashes may develop. In men, sperm production may be reduced. The body’s immune system may be impaired, and wounds may heal more slowly and less completely.
If pregnant women have zinc deficiency, the baby may have birth defects and may weigh less than expected at birth.
In acrodermatitis enteropathica, symptoms usually appear when an affected infant is weaned.
Did You Know…
Lack of zinc can weaken the immune system and make wounds heal more slowly.
Zinc deficiency is common among older people who live in institutions and people who are homebound.
Diagnosis and Treatment
Doctors suspect zinc deficiency based on the person’s circumstances, symptoms, and response to zinc supplements. Blood and urine tests do not accurately measure zinc status.
Zinc supplements are taken by mouth until symptoms disappear.
WHAT CAN CAUSE ZINC DEFICIENCY?
| CAUSE | EXAMPLES |
| Diet | Dietary deficiency of zinc is uncommon in developed countries |
| Disorders | Alcoholism Bloodstream infection (sepsis) Chronic kidney disease Diabetes mellitus Disorders that impair absorption (malabsorption) Liver disorders Lung cancer Pancreatic disorders |
| Injuries | Burns if severe |
| Treatments | Diuretics Intravenous feedings for a long time |
ZINC EXCESS
People rarely consume too much zinc. Usually, zinc excess results from consuming acidic foods or beverages packaged in a zinc-coated (galvanized) container. In certain industries, inhaling zinc oxide fumes can result in zinc excess.
People may have a metallic taste in the mouth, as well as nausea, vomiting, and diarrhea. Consuming 1 gram or more—about 70 times the recommended daily allowance (RDA)—daily may be fatal. Inhaling zinc oxide fumes can cause rapid breathing, sweating, fever, and metallic mouth taste—a disorder called metal fume fever. Consuming too much zinc for a long time can reduce the absorption of copper, cause anemia, and impair the immune system.
Doctors suspect the diagnosis based on the person’s circumstances and symptoms.
Treatment involves reducing zinc consumption. People with metal fume fever usually recover after being in a zinc-free environment for 12 to 24 hours.