Fluid and Electrolyte and Acid-Base Balance and Imbalance
Linda Felver
PRINCIPLES OF FLUID BALANCEThe fluid in the body serves many vital functions. In addition to being the milieu in which cellular chemistry occurs, it provides the transport medium for oxygen and other nutrients to reach the cells and for carbon dioxide and other metabolic waste products to be removed from the body. Technically, fluid is water plus the substances dissolved in it.
With aging, the amount of water in the body decreases. The body ranges from 70% water by weight (newborn infant) to 60% (young or middle-aged adult) to 45% (older adult woman). Women have less water by weight than men because a higher percentage of their weight is fat. Similarly, water is a lower percentage of body weight in obese people. One liter of water weighs 1 kg (2.2 lb). Thus, a standard 70-kg (154-lb) middle-aged man (60% water) has 42 L of body water (70 kg × 0.60 = 42 kg; 42 kg = 42 L).1
Body Fluid Compartments
The fluid in the body lies in several compartments. The extracellular fluid consists primarily of vascular and interstitial fluids. Some extracellular fluid is located in bone and dense connective tissue; this fluid is not considered accessible for dynamic exchange. Intracellular fluid, as the name indicates, lies in the cells. Transcellular fluid is fluid that is secreted by epithelial cells. Examples of transcellular fluid are cerebrospinal fluid (CSF), saliva, and intestinal secretions. Many of the transcellular fluids are reabsorbed by the body after they have been secreted.
More water is located inside the cells than outside of them. Clinically, approximately two thirds of body water in adults is considered intracellular and one third extracellular. Thus, the 70-kg man who has 42 L of body water can be considered to have approximately 28 L of water inside the cells and 14 L of extracellular water. This extracellular water is approximately one third vascular and two thirds interstitial. For clinical purposes, the 70-kg man can be considered to have approximately 4.5 L of water in the vascular compartment and approximately 9.5 L in the interstitial compartment.
Osmolality
The relative proportion of water to particles in body fluid is measured as osmolality. Osmolality can be considered to be the degree of concentration. Technically, osmolality is defined as the number of moles of particles per kilogram of water. The normal range of osmolality of the blood is 280 to 300 mOsm/kg (lower in normal pregnancy).2 Fluids that have osmolality within this normal range are called isotonic. Extracellular and intracellular fluids have the same osmolality. If the osmolality of the extracellular fluid is increased or decreased, then the osmolality of the intracellular fluid changes rapidly until intracellular and extracellular fluids again have the same osmolality. This process is discussed later in the “Fluid Distribution” section.
Although the osmolality of intracellular and extracellular fluids is the same, the ion composition of the two fluids differs. Thus, they have the same particle concentration, but the specific kinds of particles are different in the two fluids. Intracellular fluid has a higher concentration of protein and potassium, magnesium, and phosphate ions; extracellular fluid has a higher concentration of sodium, calcium, chloride, and bicarbonate ions.3 Transcellular fluids are usually hypotonic; their ion composition varies widely depending on their physiologic function.
Processes Involved in Fluid Balance
Fluid balance is the net result of fluid intake, fluid distribution, fluid excretion, and fluid loss by abnormal routes. Fluid balance is maintained when fluid excretion and fluid loss through any abnormal routes are matched by fluid intake and when the fluid is distributed normally into its compartments.1
Fluid Intake
The major determinant of fluid intake in a healthy adult is habit. Thirst, another important determinant of fluid intake, can be caused by several physiologic mechanisms.4 These include dryness of the oral mucous membranes, increase in osmolality of the body fluids (osmoreceptor-mediated thirst), decrease in extracellular fluid volume (ECV) (baroreceptor-mediated thirst), and increased renin secretion (angiotensin-mediated thirst). Osmoreceptor-mediated thirst is the most common cause of thirst in healthy adults. This mechanism becomes less effective with aging. Thus, older adults often have a greater need for water before they become thirsty. Cultural factors have an important influence on fluid intake. For example, intake of certain herbal teas may be considered necessary by some individuals when they become ill. Many people refuse to drink cold water when they have certain illnesses due to their cultural beliefs. In clinical settings, health care professionals often regulate the fluid intake. Routes of fluid intake include oral, rectal, intravenous, and intraosseous, as well as through tubes into body cavities. Oral fluid intake includes liquids and the water contained in food, as well as water made by cellular metabolism of ingested nutrients.
Fluid Distribution
Two types of fluid distribution operate in the body. First, fluid is distributed between the vascular and interstitial spaces, the two subcompartments of the extracellular compartment. Second, fluid
is distributed between the extracellular and intracellular compartments. Different processes regulate these two types of fluid distribution.
is distributed between the extracellular and intracellular compartments. Different processes regulate these two types of fluid distribution.
Fluid distribution between the vascular and interstitial spaces is regulated by filtration. Filtration is the net result of four opposing forces. Two of these forces tend to move fluid out of the capillaries, whereas the other two tend to move fluid into the capillaries. Which direction the fluid moves in any one location depends on which forces are stronger. The two forces that tend to move fluid out of capillaries are the blood hydrostatic pressure (outward force against the capillary walls) and the interstitial fluid osmotic pressure (inward pulling force caused by particles in interstitial fluid). The two forces that tend to move fluid into capillaries are the blood osmotic pressure (inward pulling force caused by particles in blood) and the interstitial fluid hydrostatic pressure.
Usually, the blood hydrostatic pressure is highest at the arterial end of a capillary, and there is filtration from the capillary into the interstitial fluid. This flow of fluid out of the capillaries is useful in carrying oxygen, glucose, amino acids, and other nutrients to the cells that are surrounded by interstitial fluid. Most proteins are too large to cross into the interstitial fluid and remain in the capillary. At the venous end of a capillary, the blood hydrostatic pressure is usually lower and the blood osmotic pressure higher because fluid has left the capillary but the proteins have remained. These changes cause a net flow of fluid from the interstitial space back into the venous end of a capillary. The flow of fluid back into the capillaries is physiologically useful in carrying carbon dioxide, metabolic acids, and other waste products into the blood for further metabolism or excretion.
Changes in any of the four forces that determine the direction of filtration at the capillaries can cause abnormal distribution between the vascular and interstitial compartments. The most common abnormal distribution is edema, which is expansion of the interstitial space. Edema can be caused by increased blood hydrostatic pressure (e.g., venous congestion), increased microvascular permeability that allows proteins to leak into interstitial fluid, increased interstitial fluid osmotic pressure (e.g., inflammation), decreased blood osmotic pressure (e.g., hypoalbuminemia), or blockage of the lymphatic system, which normally removes excess fluid from the interstitial space and returns it to the vascular compartment.
The second type of fluid distribution occurs between the extracellular and intracellular compartments. This process is regulated by osmosis. Cell membranes are freely permeable to water, but the passage of ions and other particles depends on membrane transport processes. Osmotic pressure is an inward-pulling force caused by particles in a fluid. Both the extracellular and intracellular fluids exert osmotic pressure. Because the osmolality of the two compartments normally is the same, the osmotic pressures are the same. Therefore, the force pulling water into the cells balances the force pulling water into the interstitial space, maintaining the normal fluid distribution. If the osmolality of the extracellular fluid changes, however, then osmosis occurs, altering the fluid distribution until the osmolality in the extracellular and intracellular compartments again is the same. For example, if the extracellular fluid becomes more concentrated (increased osmolality), then the osmotic pressure of the extracellular fluid becomes higher than the osmotic pressure of the intracellular fluid. Water leaves the intracellular compartment until the intracellular fluid becomes as concentrated as the extracellular fluid. This process decreases the amount of water that is distributed into the intracellular compartment. Similarly, if the extracellular fluid becomes more dilute (decreased osmolality), then the osmotic pressure of the extracellular fluid becomes lower than the osmotic pressure of the intracellular fluid. Water moves by osmosis into the intracellular compartment until the intracellular fluid becomes as dilute as the extracellular fluid. This process increases the amount of water that is distributed into the intracellular compartment.
In summary, fluid distribution between the vascular and interstitial compartments depends on filtration, the net result of four forces that act on fluid at the capillary level. Fluid distribution between the extracellular and intracellular compartments depends on osmosis, the movement of water across cell membranes to equilibrate particle concentrations.
Fluid Excretion
Normal routes of fluid excretion are respiratory tract, urine, feces, and skin (insensible perspiration and sweat). In a standard adult, approximately 400 mL of water is excreted daily through the respiratory tract, even if the person is fluid-depleted. This amount increases during fever. The urine volume of a healthy adult varies according to the fluid intake, the needs of the body, and the hormonal status. It averages 1,500 mL. Major hormones that regulate urinary excretion of fluid are summarized in Table 7-1. Diuretics, ethanol, and caffeine increase urine volume. Fecal excretion of water averages 200 mL per day in healthy adults who have a normal fluid balance and a fully functioning bowel. Diarrhea causes a dramatic increase in fecal excretion of water.
Insensible perspiration is fluid excretion through the skin that is not visible. It averages 500 mL per day in a healthy adult. Insensible perspiration occurs even if the person is fluid-depleted. It increases during fever. Sweat is visible fluid excretion through the skin. The volume of sweat varies greatly depending primarily on thermoregulatory needs.
Fluid Loss by Abnormal Routes
Examples of abnormal routes of fluid loss are emesis, drains, suction, paracentesis, and hemorrhage. Third-spacing (e.g., ascites) can be considered abnormal fluid loss, even though the fluid remains in the body, because the fluid is not freely available to the normal fluid compartments.
Summary of Fluid Balance
In summary, the processes of fluid intake, fluid distribution, fluid excretion, and fluid loss by abnormal routes act together to determine fluid balance or imbalances. A change in one of these processes must be matched by a change in another to maintain fluid balance. For example, if an increased urine output is matched by an increased fluid intake, then fluid balance can be maintained. If changes in one or more of these processes are not matched by changes in the others, however, then a fluid imbalance occurs. Fluid imbalances may be characterized by altered volume of fluid (ECV imbalances), altered concentration of fluid (osmolality imbalances), or a combination of both.
EXTRACELLULAR FLUID VOLUME BALANCEThe ECV is the net result of fluid intake, fluid distribution, fluid excretion, and fluid loss by abnormal routes. A normal ECV is maintained when fluid excretion and any fluid loss are balanced
by fluid intake and when the fluid distribution is normal. The body’s responsiveness to administration of a fluid load has a circadian rhythm (i.e., varies in a cyclic manner over 24 hours). The kidneys can excrete an excess fluid load more efficiently if it is administered during the time that the person is normally active than if it is administered during a person’s customary sleeping time.
by fluid intake and when the fluid distribution is normal. The body’s responsiveness to administration of a fluid load has a circadian rhythm (i.e., varies in a cyclic manner over 24 hours). The kidneys can excrete an excess fluid load more efficiently if it is administered during the time that the person is normally active than if it is administered during a person’s customary sleeping time.
Table 7-1 ▪ HORMONES THAT REGULATE RENAL FLUID EXCRETION | ||||||||||||||||||||
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The blood volume is an important determinant of the work of the heart and provides the medium for oxygen delivery to tissues. Therefore, ECV imbalances can interfere with cardiac function and tissue oxygenation.
Extracellular Fluid Volume Deficit
ECV deficit is caused by removal of sodium-containing fluid from the vascular and interstitial spaces. Usually, the fluid is removed from the body; however, in some cases, fluid is sequestered in the peritoneal cavity, the intestinal lumen, or some other “third space.” ECV deficits occur when intake of sodium-containing fluid does not keep pace with increased fluid excretion or loss of fluid through abnormal routes. Clinical causes of ECV deficit are presented in Table 7-2. ECV deficit may develop in people with cardiac disease who use diuretics if the dosage is excessive.
Clinical manifestations of ECV deficit include sudden weight loss (unless there is third-spacing), poor skin turgor, dryness of opposing mucous membranes, hard dry stools, longitudinal furrows in the tongue, absence of tears and sweat, and soft sunken eyeballs. Although weight loss occurs immediately, most of these signs appear only after substantial fluid depletion. Cardiovascular manifestations are among the early signs; these are discussed next.
Many of the clinical manifestations of ECV deficit are evident in the cardiovascular system. Decreased volume in the vascular compartment causes postural blood pressure drop with postural tachycardia, delayed capillary refill, prolonged small vein filling time, flat neck veins when supine (or neck veins that collapse during inspiration), and decreased central venous pressure.
A postural blood pressure drop is assessed by measuring blood pressure and heart rate with the individual supine and then standing or sitting with the legs dependent (not horizontal). If both systolic and diastolic blood pressures decrease substantially and heart rate increases substantially, then these postural changes are due to ECV deficit. The increased heart rate indicates that autonomic reflexes are functioning and rules out autonomic insufficiency, which may cause an upright blood pressure to decrease when the ECV is normal. Postural blood pressure drop is not a reliable assessment for ECV deficit in individuals who have a transplanted heart. The heart rate may not increase in these individuals when their blood pressure drops from ECV deficit.
Small vein filling time is assessed by placing an individual’s hand or foot below the level of the heart, occluding a small vein, milking it flat by stroking toward the heart, and then releasing it. If the vein takes longer than 3 to 5 seconds to refill, then the person probably has an ECV deficit (unless occlusive arterial disease is present).
Table 7-2 ▪ CAUSES OF EXTRACELLULAR FLUID VOLUME DEFICIT | ||||||||
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Table 7-3 ▪ CAUSES OF EXTRACELLULAR FLUID VOLUME EXCESS | ||||||
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The decreased preload of ECV deficit leads to decreased cardiac output, with resulting dizziness, syncope, and oliguria. If ECV deficit becomes severe, tachycardia, pallor caused by cutaneous vasoconstriction, and other manifestations of hypovolemic shock occur (see Chapter 24).
Extracellular Fluid Volume Excess
Excess ECV is an overload of fluid in the vascular and interstitial compartments. It is common in individuals with heart failure because their decreased cardiac output activates the renin-angiotensin-aldosterone system.5 Aldosterone causes renal retention of sodium and water, which expands the extracellular volume. People who have hypertension caused by elevated renin also develop ECV excess. Other causes of ECV excess are listed in Table 7-3. Clinical manifestations of ECV excess include sudden weight gain, peripheral edema, and the cardiovascular effects described next.
Increased vascular volume is manifested by bounding pulse, distended neck veins when upright, and elevated central venous pressure. The crackles, dyspnea, and orthopnea of pulmonary edema may be present. A sudden overload of isotonic fluid increases cardiac work and may cause heart failure, especially in an older adult or an infant.
OSMOLALITY BALANCEThe osmolality of body fluids is determined by the relative proportion of particles and water. The serum sodium concentration usually parallels the osmolality of the blood. When the serum sodium concentration is abnormally low, the osmolality is decreased; in other words, the blood is relatively too dilute. Conversely, when the serum sodium concentration is elevated, the osmolality is increased; in that case, the blood is relatively too concentrated. Antidiuretic hormone (ADH), also called vasopressin, (see Table 7-1) is the major regulator of osmolality.6
Hyponatremia
Hyponatremia is a relative excess of water that causes a decreased serum sodium concentration. It is caused by a gain of water relative to salt or a loss of salt relative to water (Table 7-4). ADH increases the reabsorption of water by the renal tubules and thus dilutes body fluids. In people who have had cardiac surgery, hyponatremia may occur in the first few days after surgery if excess free water is administered because the stressors of surgery, anesthesia, pain, and nausea increase the secretion of ADH.1 Hyponatremia is common in individuals with chronic heart failure because their decreased cardiac output stimulates arterial baroreceptors, triggering nonosmotic release of ADH.7 Diuretic therapy also contributes to hyponatremia, as discussed below. Hyponatremia in hospitalized heart failure patients is associated with longer hospitalization and increased in-hospital and postdischarge mortality.8, 9, 10 Although clinical trials have shown that vaptans, aquaretic drugs that block vasopressin receptors in the kidney, are capable of correcting hyponatremia in hyponatremic heart failure patients, no improvement in morbidity or mortality have been demonstrated.11,12 In people with either ST-elevation myocardial infarction (MI) or suspected acute coronary syndrome, non-ST-elevation MI, hyponatremia is associated with adverse outcomes such as death or recurrent MI.13
Table 7-4 ▪ CAUSES OF HYPONATREMIA | ||||||||||||||
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The most common medications used by people with cardiovascular disease that may cause hyponatremia are diuretics, especially the thiazide diuretics and the thiazide-like diuretic indapamide.14, 15, 16 Hyponatremia from thiazide diuretics occurs more frequently in women than men, especially in older women.17
The hypo-osmolality of hyponatremia causes water to enter cells by osmosis. The clinical manifestations of hyponatremia are primarily nonspecific markers of cerebral dysfunction: malaise, confusion, lethargy, seizures, and coma. The extent of these manifestations depends on the speed with which hyponatremia develops as well as its severity. Hyponatremia does not have significant clinical effects on cardiac electrophysiology or function.
Hypernatremia
Hypernatremia is a relative deficit of water that causes an increased serum sodium concentration. It is caused by a loss of water relative to salt or a gain of salt relative to water (Table 7-5). The hyperosmolality of hypernatremia causes water to leave cells by osmosis. The clinical manifestations are similar to those of hyponatremia:
malaise, confusion, lethargy, seizures, and coma.3 Thirst (except in some older adults) and oliguria (except in hypernatremia caused by decreased ADH) may also occur. As with hyponatremia, the extent of these manifestations depends on the speed with which hypernatremia develops as well as its severity. Hypernatremia is much less common than hyponatremia in cardiac patients who do not have other pathophysiologies, although it is common in critically ill patients.18 Hypernatremia also does not have significant clinical effects on cardiac electrophysiology or function.
malaise, confusion, lethargy, seizures, and coma.3 Thirst (except in some older adults) and oliguria (except in hypernatremia caused by decreased ADH) may also occur. As with hyponatremia, the extent of these manifestations depends on the speed with which hypernatremia develops as well as its severity. Hypernatremia is much less common than hyponatremia in cardiac patients who do not have other pathophysiologies, although it is common in critically ill patients.18 Hypernatremia also does not have significant clinical effects on cardiac electrophysiology or function.
Table 7-5 ▪ CAUSES OF HYPERNATREMIA | ||||||
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Mixed ECV and Osmolality Imbalances
ECV and osmolality imbalances may occur at the same time in the same person. For example, in a person who has severe gastroenteritis without proper fluid replacement, concurrent ECV deficit and hypernatremia (clinical dehydration) will develop. The fluid lost in the emesis and diarrhea, plus the usual daily fluid excretion (urine, feces, respiratory, insensible through skin), is hypotonic sodium-containing fluid (analogous to isotonic saline that has extra water added). People who have chronic heart failure frequently develop concurrent ECV excess and hyponatremia, sometimes called a hypervolemic hyponatremia.12
The signs and symptoms of such mixed fluid imbalances are a combination of the clinical manifestations of the two separate imbalances. In the example of clinical dehydration, the individual has the sudden weight loss, manifestations of decreased vascular volume, and signs of decreased interstitial volume that result from ECV deficit plus the thirst and nonspecific signs of cerebral dysfunction that result from hypernatremia.3 In heart failure, the clinical manifestations include the weight gain, distended neck veins, and edema of ECV excess plus the nonspecific signs of cerebral dysfunction of hyponatremia.
PRINCIPLES OF ELECTROLYTE BALANCEElectrolyte balance is the net result of several concurrent dynamic processes. These processes are electrolyte intake, absorption, distribution, excretion, and loss through abnormal routes1 (Table 7-6). Electrolyte intake in healthy people is primarily by the oral route; other routes of electrolyte intake include the intravenous and rectal routes, and also through tubes into various body cavities. Electrolytes that are taken into the gastrointestinal tract must be absorbed into the blood. Although some electrolytes (e.g., potassium) are absorbed readily by mechanisms based on gradients, the absorption of other electrolytes (e.g., calcium and magnesium) is more complex and can be impaired by many factors.
Electrolytes are distributed into all body fluids, but their concentrations in the different body fluid compartments vary greatly. Substantial amounts of most electrolytes are located in pools outside the extracellular fluid. For example, the major pool of potassium is inside cells; the major pool of calcium is in the bones.
Electrolyte excretion occurs through the normal routes of urine, feces, and sweat. Any removal of electrolytes through other routes can be considered loss of electrolytes through an abnormal route. Examples of these abnormal routes are emesis, nasogastric suction, fistula drainage, and hemorrhage.
To maintain normal balance of any specific electrolyte, electrolyte intake and absorption must equal electrolyte excretion and electrolyte loss through abnormal routes, and the electrolyte must be distributed properly within the body. Alterations in any of these processes can cause an electrolyte imbalance.1
ELECTROLYTE IMBALANCESPlasma electrolyte imbalances can have profound effects on cardiovascular function. Because cardiac function depends on ion currents across myocardial cell membranes, action potential generation, impulse conduction, and myocardial contraction are all vulnerable to alterations in electrolyte status. In addition to their effects on the myocardium itself, some electrolyte imbalances have vascular effects.
Potassium Balance
Potassium balance is the net result of potassium intake and absorption, distribution, excretion, and abnormal losses. These components are summarized in Table 7-6. Although the plasma potassium concentration describes the status of potassium in the extracellular fluid, it does not necessarily reflect the amount of potassium inside the cells. The plasma potassium concentration has a circadian rhythm, rising during the hours a person is usually active and reaching its trough when a person is usually asleep. A classic study demonstrated that the kidneys handle an intravenous potassium load much less efficiently during the hours a person is customarily asleep, which has implications for potassium administration to ICU patients.19
The potassium concentration of the extracellular fluid has a major influence on the function of the myocardium. Specifically, the resting membrane potential of cardiac cells is proportional to the ratio of potassium concentrations in the extracellular and intracellular fluids. The potassium concentration within cardiac cells is approximately 140 mEq/L; the normal potassium concentration of the extracellular fluid is 3.5 to 5 mEq/L. A small change in the extracellular concentration of potassium has a large effect on the extracellular-to-intracellular concentration ratio because the initial extracellular value is relatively small. A similar change in the intracellular potassium concentration has a lesser effect because the initial intracellular value is so large.
Table 7-6 ▪ ELECTROLYTE HOMEOSTASIS | ||||||||||||||||||||||||||||||||||||
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Hypokalemia
Hypokalemia, a decrease in the plasma potassium concentration, is caused by decreased potassium intake, shift of potassium ions from the extracellular fluid into the cells, increased excretion of potassium, loss of potassium through an abnormal route, or any combination of these factors.1 Some specific etiologic factors in these categories are listed in Table 7-7. Hypokalemia is common in people with heart failure because of their increased secretion of aldosterone and their diuretic therapy, and it is associated with increased mortality in ambulatory people who have chronic heart failure.20,21
Table 7-7 ▪ CAUSES OF HYPOKALEMIA | ||||||||||||
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Catecholamines and β-agonist drugs cause potassium ions to shift into cells by a β2-adrenergic mechanism. This effect can produce hypokalemia.22,23 Plasma catecholamines increase rapidly during MI and hypokalemia is common during acute coronary syndromes.24 This hypokalemic effect is not as strong in people who have diabetic autonomic neuropathy.24 Transient hypokalemia associated with catecholamine release during an MI may cause further impairment of an already compromised myocardium (see Chapter 5).
The increased potassium excretion caused by many types of diuretics is well known.21,25 Hypokalemia caused by diuretic therapy occurs most frequently within 2 to 8 weeks, although it may arise after more than 1 year.26 The necessity of monitoring the plasma potassium concentration in individuals using diuretics, especially older adults, is clear.27 Individuals with hypokalemia have significantly more ventricular arrhythmias after MI than do normokalemic individuals. The hypokalemic effect of catecholamines is stronger in people who are using thiazide diuretics than it is in those who are not using diuretics.
Because of the cardiac effects of hypokalemia, the National Council on Potassium in Clinical Practice has established guidelines for potassium replacement.28 For individuals with hypertension, the guideline is to maintain a serum potassium concentration of at least 4.0 mEq/L. Potassium replacement should be considered routinely in people with congestive heart failure, even with a serum potassium level of 4.0 mEq/L. Potassium levels of at least 4.0 mEq/L are necessary in individuals who have cardiac arrhythmias. The guidelines also emphasize the necessity of routine monitoring of serum potassium in people who have congestive heart failure or cardiac arrhythmias.
Clinical manifestations of hypokalemia include diminished bowel sounds, abdominal distention, constipation, polyuria, skeletal muscle weakness, flaccid paralysis, cardiac arrhythmias, and postural hypotension. Cardiac and vascular effects of hypokalemia are discussed next.
Cardiac Effects of Hypokalemia.
The cardiac effects of hypokalemia include changes in cell membrane resting potential. When the extracellular potassium concentration decreases, the extracellular/intracellular potassium concentration ratio decreases. This change in ratio causes cardiac muscle cells to hyperpolarize (i.e., the resting membrane potential becomes more negative). In hyperpolarized cells, the distance between resting potential and action potential is increased; hyperpolarized cells are less responsive to stimuli than are normal cells. The hyperpolarizing effect of hypokalemia on cardiac cells does not occur at all levels of hypokalemia. At low plasma potassium concentrations, a hypopolarizing effect may be seen. This is probably caused by decreased potassium conductance (analogous to decreased potassium permeability) of the cell membrane. The specific alteration of cardiac cell membrane resting potential thus depends on the degree of hypokalemia. In any case, the normal resting potential is altered, which contributes to the development of arrhythmias.
In addition to its effect on cell membrane resting potential, hypokalemia increases the rate of cardiac cell diastolic depolarization.29 Diastolic depolarization is the normal mechanism that initiates the depolarization of pacemaker cells (see Chapter 16). Under usual circumstances, diastolic depolarization is fastest in the sinus node cells; consequently, the sinus node serves as the predominant pacemaker. During hypokalemia, however, the rate of diastolic depolarization increases in other myocardial cells, especially in diseased myocardium. Ectopic beats may arise, even from hyperpolarized cells.
Other effects of hypokalemia on the myocardium also predispose to arrhythmias. Hypokalemia decreases conduction velocity, especially in the atrioventricular node. Hypokalemia prolongs the action potential by decreasing the rate of repolarization, at least in part by decreasing cardiac cell membrane permeability to potassium efflux.30,31 It alters the normal relationship between action potential duration in the epicardium and the endocardium, which may contribute to cardiac arrhythmias, and decreases the ventricular effective refractory period, which predisposes to the development of extrasystoles and reentrant arrhythmias (see Chapter 16).31, 32, 33
The cardiac alterations of hypokalemia may cause many types of arrhythmias. Hypokalemia-induced arrhythmias include supraventricular premature depolarizations and tachycardias, ventricular ectopic beats, ventricular tachycardia, torsade de pointes, and ventricular fibrillation.34, 35, 36, 37, 38, 39 Hypokalemia potentiates digitalis toxicity. Animal studies indicate that downregulation of gap junction proteins in diabetic cardiomyopathy increases the vulnerability to ventricular fibrillation in hypokalemia.40
As might be expected from the previous discussion, electrocardiographic (ECG) changes are seen in individuals with hypokalemia (see Chapter 16). A characteristic change is the development of U waves.41,42 Other ECG changes include increased amplitude of P waves, prolonged PR interval, prolonged QT interval, flattened or inverted T waves, and ST segment depression.23,32,35,36,42,43
Long-standing hypokalemia is associated with selective myocardial cell necrosis. As discussed in Chapter 27, selective myocardial cell necrosis is associated with sudden cardiac death.
Vascular Effects of Hypokalemia.
In addition to the multiple cardiac effects discussed previously, hypokalemia has vascular effects. Postural hypotension often occurs in hypokalemia,3 most likely caused by impaired smooth muscle function.
Hyperkalemia
Hyperkalemia, an increased plasma potassium concentration, results from increased potassium intake, shift of potassium ions from the cells to the extracellular fluid, decreased potassium excretion, or any combination of these factors.1 Examples of specific etiologic factors in each of these categories are listed in Table 7-8. Hyperkalemia may occur during hemorrhagic or hypovolemic shock and during cardiopulmonary resuscitation.
Several medications commonly administered to individuals with cardiac disease may cause hyperkalemia.48 Angiotensin-converting enzyme inhibitors such as captopril and enalapril, angiotensin II receptor blockers such as losartan, selective aldosterone blockers such as eplerenone, and direct renin inhibitors such as aliskiren decrease the release of aldosterone. Aldosterone normally facilitates renal excretion of potassium. When these drugs decrease the availability of aldosterone, hyperkalemia may occur.49, 50, 51, 52 The potassium-sparing diuretics spironolactone, triamterene, and amiloride may cause hyperkalemia, especially if given with potassium supplementation or angiotensin-converting enzyme inhibitors or used by people who have any degree of renal impairment.50,51,53,54 Nonselective β-adrenergic blockers promote the development of hyperkalemia by blocking catecholamine action at β2 receptors that normally stimulates potassium entry into cells.49,56 The hyperkalemic effect of β-blockade is especially pronounced during exercise, which has relevance to treadmill stress testing, and is enhanced in people who take digitalis.48,56,57 Administration of either unfractionated or low-molecular-weight heparin, even in low-dose therapy, decreases the synthesis of aldosterone; hyperkalemia is likely to occur in heparinized individuals who have even mild renal insufficiency.48,58 A massive digitalis overdose causes hyperkalemia by allowing intracellular potassium to leak into the extracellular fluid and impairing its movement back into cells.52
Table 7-8 ▪ CAUSES OF HYPERKALEMIA | ||||||||||
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Another cardiovascular-related source of hyperkalemia is massive blood transfusion. While blood is stored, potassium ions leak from the erythrocytes into the plasma. The longer the storage time, the greater the potassium load contained in a unit of blood.59,60 A classic study indicates that if the blood has been in storage for more than 3 days, rewarming the blood before administration causes only minimal return of potassium to the cells.61 Individuals receiving more than 7 or 8 units of stored blood within a few hours are considered at high risk for severe hyperkalemia; however, fatal hyperkalemia has occurred with transfusion of fewer units, especially when they are administered rapidly.60,62
Hyperkalemia may be manifested clinically by intestinal cramping and diarrhea, skeletal muscle weakness, flaccid paralysis, cardiac arrhythmias, and cardiac arrest. The cardiac effects of hyperkalemia are potentially fatal; they are discussed in the next section.
Cardiac Effects of Hyperkalemia.
Hyperkalemia alters myocardial cell function in several ways. When the plasma potassium concentration increases, the extracellular/intracellular potassium concentration ratio increases. Consequently, the resting membrane potential of cardiac cells becomes partially depolarized (hypopolarized).48 Initially, the partial depolarization of resting cardiac cells increases their excitability because the resting potential is close to threshold potential (see Chapter 16). As the extracellular potassium concentration increases, however, the cardiac cells depolarize to the extent that they cannot repolarize. Cells in this state are nonexcitable; no further contractile activity occurs. The ability of hyperkalemia to cause asystolic cardiac arrest is exploited by using potassium as a cardioplegic agent during cardiac surgery.63
Other effects of hyperkalemia include decreased duration of the action potential at all heart rates and increased rate of repolarization, the latter due to increased permeability of the cardiac cell membrane to potassium efflux.32 Hyperkalemia lengthens the effective refractory period of atrial muscle and slows diastolic depolarization of pacemaker cells, two antiarrhythmic effects. Cardiac cells vary in their sensitivity to the effects of hyperkalemia. Atrial cells are more sensitive than ventricular cells; the conduction system is the last to be affected.48
As the plasma potassium increases, the rate of rise of the action potential decreases. Slow upstroke velocity decreases cell-to-cell conduction velocity (see Chapter 16). Hyperkalemia decreases conduction velocity at all levels of the conduction system: atrial, atrioventricular nodal, and intraventricular.48,52 In severe hyperkalemia, intraventricular conduction may be completely inhibited. Bundle-branch block or, less frequently, complete heart block may occur.42,64
Although some of the cellular effects of hyperkalemia are antiarrhythmogenic, cardiac arrhythmias do occur in hyperkalemia. The differential effects of hyperkalemia on different cell types cause slow and nonhomogeneous conduction to cells with variable degrees of excitability. When intra-atrial conduction is decreased, sinus node impulses may be delayed in exit or may fail to propagate. This situation gives rise to Wenckebach (type I) or Mobitz (type II) sinoatrial block (see Chapter 16). Reentrant ventricular arrhythmias may arise. Ventricular tachycardia may terminate in ventricular fibrillation.42 Asystolic cardiac arrest also is a potentially fatal event.39
The characteristic ECG changes of hyperkalemia arise from the electrophysiologic changes previously described. The initial ECG abnormality is the T waves becoming peaked (tented) with a narrow base and symmetric shape.65,66 The QRS complex widens; ST depression may occur. Occasionally, ST elevation occurs, mimicking an MI.67, 68, 69 Hyperkalemia also causes decreased amplitude and prolongation of P waves and PR prolongation.70,71 As the plasma potassium concentration increases to high levels, the P waves disappear. A sine-wave pattern appears in severe, often terminal, hyperkalemia.39,42,72
The ECG changes of hyperkalemia are not well correlated with plasma potassium levels.42,73,74 Although the ECG usually is abnormal with severe hyperkalemia (serum potassium greater than 8 mEq/L), minimal ECG changes have been observed in individuals with serum potassium concentrations greater than 9 mEq/L. The rate of increase of the plasma potassium concentration may contribute more to the ECG changes in hyperkalemia than does the absolute plasma potassium level. Hemodialysis patients may not exhibit the characteristic peaked T wave or other ECG signs when they are severely hyperkalemic. This may be caused in part by concurrent hypercalcemia, which can flatten the T wave.75 The ECG changes of hyperkalemia also are blunted during hypothermia.76
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