A 70-kg adult has about 100 g of sodium, 95 g of chloride, and 140 g of potassium in the body (Forbes, 1987). Distribution of these electrolytes within the various fluid compartments and body tissues is highly variable in terms of concentration and content. Sodium and chloride are the major electrolytes found predominantly in extracellular fluid, whereas potassium is retained inside the cells (Figure 34-1). The concentration of sodium ions (Na+) in the extracellular fluid, and thus in the plasma, is maintained within narrow limits at approximately 145 mmol/L. Its concentration in the intracellular fluid is low, about 12 mmol/L. Distribution of chloride ions (Cl–) generally follows that of Na+, with an extracellular concentration of about 110 mmol/L and an intracellular concentration of about 2 mmol/L. About one third of the body’s sodium is sequestered as part of the integral structure of skeleton and therefore is not available for exchange with the fluid compartments. The concentration of potassium ions (K+) is 150 mmol/L inside the cells and 4 to 5 mmol/L in the extracellular fluid. The largest fraction of body potassium, about 60% to 70% of the total, is located in the skeletal muscles, which make up about 40% of body weight. The high concentration gradient of K+ between the intracellular and extracellular fluid is important for maintaining the normal resting membrane potential across cell membranes and for excitability of nerves and muscles. It plays a crucial role in the triggering of action potentials that initiate nerve impulse transmission and muscle contraction. Changes in the concentration of K+ in the plasma alter this gradient and will adversely affect the aforementioned functions (Rodriguez-Soriano, 1995). For instance, in hyperkalemia, when the concentration of K+ in the plasma exceeds 5.5 mmol/L, the membrane depolarizes, causing muscle weakness, flaccid paralysis, and cardiac dysrhythmias. Cardiac dysrhythmias associated with hyperkalemia range from sinus bradycardia to ventricular tachycardia, ventricular fibrillation, and ultimately cardiac arrest (asystole) when a plasma concentration of 8 mmol/L is reached. Because of the adverse effects of hyperkalemia on the heart, hyperkalemia constitutes a medical emergency. In contrast, in hypokalemia, when the concentration of K+ in the plasma is less than 3.5 mmol/L, the membrane hyperpolarizes, and this can interfere with the normal functioning of nerves and muscles, resulting in muscle weakness and decreased smooth muscle contractility. Hypokalemia is also a risk factor for atrial and ventricular dysrhythmias (He and MacGregor, 2008). Severe hypokalemia can lead to paralysis, metabolic alkalosis, and death. Therefore physiological regulatory mechanisms are present to regulate the concentration of K+ in the plasma within narrow limits. Activators of enzyme-catalyzed reactions are frequently metal ions such as magnesium (Mg2+), zinc (Zn2+), manganese (Mn2+), and calcium (Ca2+); only a limited number of enzymes require the presence of Na+, K+, or Cl–. The most common and most widely distributed enzyme in the cell membrane is the Na+,K+-ATPase, the activation of which requires the presence of Na+ and K+. Enzymes that require the presence of Cl– for activation include the angiotensin-converting enzyme (ACE) that catalyzes the conversion of angiotensin 1 to angiotensin 2 (Bunning and Riordan, 1987). Although the presence of Mg2+ is required for activation of a number of enzymes by K+ in mammalian tissues, K+ by itself is important for the activity of pyruvate kinase (Larsen et al., 1994). Obligatory loss of fluids through skin, feces, and urine inevitably causes loss of sodium and chloride (see Chapter 35). Minimum obligatory loss of sodium in the absence of profuse sweating and gastrointestinal and renal diseases has been estimated to be approximately 0.04 to 0.185 g/day, which consists of 0.005 to 0.035 g/day in urine, 0.01 to 0.125 g/day in feces, and dermal losses of 0.025 g/day (Dahl, 1958). Studies over a 12-day period have shown that sweat and fecal excretion accounted for only 2% to 5% of total sodium excretion in adults who consume an average intake of salt; the remainder of the salt consumed was excreted in the urine (Sanchez-Castillo et al., 1987b). However, loss of sodium can increase greatly under certain circumstances, such as diarrhea, diabetes, and profuse sweating during strenuous physical activity in hot weather. Under most but not all circumstances, loss of sodium is accompanied by a similar molar loss of chloride. Americans consume between 1.8 and 5 g/day of sodium or between 4.8 and 13 g/day of sodium chloride (National Research Council, 1989). This wide range of reported intakes is due to the different methods of assessment and to the large variability of discretionary salt intake. Individuals consuming a diet high in processed foods have high salt intakes. In Japan, where consumption of salt-preserved fish and the use of salt for seasoning are customary, salt intake is high, ranging from 14 to 20 g/day (Kono et al., 1983). Conversely, salt consumption estimated from urinary sodium excretion of the Yanomami Indians in Brazil is very low, 0.053 g/day of sodium chloride (Mancilha-Carvalho and Souza e Silva, 2003). Vegetarians typically consume an average of 0.8 g/day of sodium chloride. Individuals with low or very low sodium intakes do not normally exhibit chronic deficiencies because of the efficiency of the body’s mechanism of salt conservation. Development of hypertension appears to be associated with salt intake. Several trials have demonstrated that dietary sodium intake close to the AI (e.g., 1.2 g/day) was associated with lower blood pressure, compared to higher intakes (e.g., 2.3 g/day) (Johnson et al., 2001; Sacks et al., 2001; MacGregor et al., 1989). Based on these studies, the IOM (2004) has set a Tolerable Upper Intake Level (UL) for adults of 2.3 g (100 mmol)/day of sodium and 3.6 g (100 mmol)/day of chloride. The ULs for young children are somewhat lower. 2.8 g potassium per teaspoon as potassium chloride. Because of the growing evidence of the beneficial effects of potassium in protecting against cardiovascular diseases and reducing cardiovascular disease mortality, concern of possible underconsumption of potassium has led to recommendations for increased intake of dietary fruits and vegetables (He and MacGregor, 2008). To replace the obligatory loss of potassium, an adult should consume not less than 0.8 g/day of potassium. The IOM (2004) did not set an EAR or RDA for potassium because of insufficient dose–response data to establish an EAR. The adult AI for potassium was set at 4.7 g/day based upon the dietary level that would blunt the severe salt sensitivity prevalent in black men (Morris et al., 1999). This level of AI for potassium intake is also associated with a lower blood pressure, lower risk of kidney stones, and decreased bone loss. No increment was added to the AI for pregnant women, but the AI for lactating women was increased to 5.1 g/day to allow for the potassium content in human milk secreted during the first 6 months of lactation. Based on the NHANES III data, the percentage of adults who consume an amount of potassium that is equal to or greater than the AI is only 10% for men and less than 1% for women in the United States (IOM, 2004). A diet rich in fruits and vegetables is necessary to obtain the AI for potassium from natural foods. No important receptors capable of detecting the amount of sodium in the body have been identified. However, because Na+ is the main determinant of extracellular fluid volume, physiological mechanisms that control the volume of extracellular fluid effectively maintain a balance for sodium and chloride (Hall, 2011c). Changes in extracellular fluid volume lead to corresponding changes in the effective circulating volume and affect the “fullness” or “pressure” in the circulation. This changes cardiac filling pressure, cardiac output, and arterial pressure. Volume or pressure sensors (baroreceptors) that detect these changes are located throughout the vascular system. These baroreceptors send either excitatory or inhibitory signals to the central nervous system and the endocrine glands to effect appropriate responses by the kidneys to match the amount of sodium ingested. Three major mechanisms participate in the regulation of sodium balance: (1) vascular pressure receptors and their efferent renal sympathetic and arginine vasopressin (AVP) pathways, (2) the renin–angiotensin–aldosterone system, and (3) natriuretic peptides. Two of these mechanisms, vascular pressure receptors and their corresponding efferent pathways, and the renin–angiotensin–aldosterone system, respond effectively to hypovolemia by conservation of body sodium and water, whereas the natriuretic peptides are effective in hypervolemia when excess sodium and water are excreted in the urine (Hall, 2011b, 2011c, 2011d).
Sodium, Chloride, and Potassium
Functions and Distribution of Sodium, Chloride, and Potassium
Distribution in the Body
Importance of Potassium
Other Functions of Electrolytes
Interactions with Macroions
Activation of Enzymes
Sodium, Chloride, and Potassium Balance
Loss of Sodium, Chloride, and Potassium
Intake of Sodium and Chloride
Dietary Intake
Recommended Intake
Intake of Potassium
Dietary Intake
Recommended Intake
Regulation of Sodium, Chloride, and Potassium Balance
Renal Excretion of Sodium, Chloride, and Potassium
Control of Renal Excretion of Sodium and Chloride
