The Cellular Environment
Fluids and Electrolytes, Acids and Bases
The cells of the body live in a fluid environment that requires electrolyte and acid-base concentrations maintained within a very narrow range. A balance is maintained by an integration of renal, hormonal, and neural functions. Changes in the composition of electrolytes affect electrical potentials of excitatory cells and cause shifts of fluid from one compartment to another that can affect cell function. Fluid fluctuations also affect blood volume and therefore blood pressure. Alterations in pH (measure of the acidity or alkalinity of a solution) disrupt the cellular function of enzyme systems and can cause cell injury. Disturbances in fluid and electrolyte or acid-base balance are common and can be life threatening. Understanding how alterations occur and the body’s ability to compensate or correct the disturbance is important for comprehending many pathophysiologic conditions.
The fluids of the body are distributed among functional compartments, or spaces, and provide a transport medium for cellular and tissue function. Water moves freely among body compartments and is distributed by osmotic and hydrostatic forces. Two thirds of the body’s water is intracellular fluid (ICF) and one third is in the extracellular fluid (ECF) compartments. The two main ECF compartments are the interstitial fluid and the intravascular fluid, the latter being the blood plasma. Other ECF compartments include the lymph and the transcellular fluids, such as the saliva, intestinal, biliary, hepatic, pancreatic, and cerebrospinal fluids; sweat; urine; and pleural, synovial, peritoneal, pericardial, and intraocular fluids (Table 3-1).
|FLUID||Na+ (mEq/L)||K+ (mEq/L)||Cl− (mEq/L)||(mEq/L)|
The sum of fluids within all compartments constitutes the total body water (TBW) (Table 3-2). The volume of TBW is usually expressed as a percentage of body weight in kilograms. The standard value for TBW is 60% of the weight of a 70-kg adult male, which is equivalent to 42 L of fluid (Table 3-3). The rest of the body weight is composed of fat and fat-free solids, particularly bone.
|PERCENTAGE OF BODY WEIGHT||VOLUME (L)|
|Intracellular fluid (ICF)||40||28|
|Extracellular fluid (ECF)||20||14|
|Total body water (TBW)||60||42|
|BODY BUILD||TBW (%) ADULT MALE||TBW (%) ADULT FEMALE||TBW (%) INFANT|
Although daily fluid intake may fluctuate widely, the body regulates water volume within a relatively narrow range. The primary sources of body water are drinking of fluids, ingestion of water in food, and derivation of water from oxidative metabolism. Normally, the largest amounts of water are lost through renal excretion. Lesser amounts are eliminated through the stool and through vaporization from the skin and lungs (insensible water loss) (Table 3-4).
|DAILY INTAKE (ml)||DAILY OUTPUT (ml)|
|Drinking ≈60%||1400-1800||Urine ≈60%||1400-1800|
|Water in food ≈30%||700-1000||Stool ≈2%||100|
|Water of oxidation ≈10%||300-400||Skin ≈10%||300-500|
Although the amount of fluid within the various compartments is relatively constant, exchange of solutes (e.g., salts) and water occurs between compartments to maintain their unique compositions. The percentage of TBW varies with the amount of body fat and age. Because fat is water repelling (hydrophobic), very little water is contained in adipose cells. Individuals with more body fat have proportionately less TBW and tend to be more susceptible to fluid imbalances that cause dehydration.
The distribution and amount of TBW change with age (see Table 3-3). In newborn infants, TBW is about 75% to 80% of body weight because infants store less fat. In the immediate postnatal period, a physiologic loss of body water occurs, equivalent to about 5% of body weight as the infant adjusts to a new environment. Infants are particularly susceptible to significant changes in TBW because of their high metabolic rate and potential for evaporative fluid loss attributable to their greater body surface area in proportion to total body size. Loss of fluids from diarrhea can represent a significant proportion of body weight in infants. Renal mechanisms that regulate fluid and electrolyte conservation may not be mature enough to counter the losses, so dehydration can develop rapidly.
During childhood, TBW slowly decreases to 60% to 65% of body weight. At adolescence the percentage of TBW approaches adult proportions, and gender differences begin to appear. Males eventually have a greater percentage of body water as a function of increasing muscle mass. Females have more body fat and less muscle as a function of estrogens and therefore have less body water.
With increasing age the percentage of TBW declines further still. The decrease is caused in part by an increased amount of fat and a decreased amount of muscle and by a reduced ability to regulate sodium and water balance. With older age the kidneys becomes less efficient at conserving sodium and therefore have difficulty concentrating the urine. Insensible water loss through the skin may increase and thirst perception may be impaired. The normal reduction of TBW in older adults becomes clinically important when the body is under stress, such as development of fever or dehydration; loss of body fluids at such times can be severe and life threatening.1
The movement of water between ICF and ECF compartments is primarily a function of osmotic forces. (Osmosis and other mechanisms of passive transport are discussed in Chapter 1.) Water moves freely by diffusion through the lipid bilayer cell membrane and through aquaporins, a family of water channel proteins that provide permeability to water.2 The osmolality (number of osmoles of solute per kilogram of fluid [Osm/kg]) of TBW is normally at equilibrium. Sodium is responsible for the osmotic balance of the ECF space. Potassium maintains the osmotic balance of the ICF space. The osmotic force of ICF proteins and other nondiffusible substances is balanced by the active transport of ions out of the cell. Water crosses cell membranes freely so the osmolality of TBW is normally at equilibrium. Normally the ICF is not subject to rapid changes in osmolality but when ECF osmolality changes, water moves from one compartment to another until osmotic equilibrium is reestablished (see Figure 3-6, p. 110).
The distribution of water and the movement of nutrients and waste products between the plasma in the tissue capillaries and interstitial spaces occur as a result of changes in hydrostatic pressure and osmotic forces at the arterial and venous ends of the capillary. Water, sodium, and glucose move readily across the capillary membrane. The plasma proteins maintain the effective osmolality (concentration of solutes per kilogram of solution), do not cross the capillary membrane, and generate plasma oncotic pressure. Albumin is the plasma protein that is primarily responsible for the plasma oncotic pressure because it has the highest concentration. Osmotic forces within the capillary are balanced by the hydrostatic pressure, which is primarily determined by blood pressure and blood volume.
As plasma flows from the arterial to the venous end of the capillary, four forces determine if fluid moves out of the capillary and into the interstitial space (filtration) or if fluid moves back into the capillary from the interstitial space (reabsorption):
Normally the interstitial forces are negligible because only a very small percentage of plasma proteins crosses the capillary membrane and interstitial fluid moves into cells or is drawn back into the plasma. Thus the major forces for filtration are within the capillary.
As the plasma flows from the arterial to the venous end of the capillary, the force of hydrostatic pressure facilitates the movement of water across the capillary membrane. Oncotic pressure remains fairly constant because plasma proteins normally do not cross the capillary membrane. At the arterial end of the capillary, hydrostatic pressure is greater than capillary oncotic pressure and water filters into the interstitial space. Because of oncotic forces, some water moves back into the capillary, but the net effect is loss of water from the capillary. This loss of water from the plasma decreases the hydrostatic pressure within the capillary; thus at the venous end of the capillary, oncotic pressure exceeds hydrostatic pressure. Fluids then are attracted back into the circulation, balancing the movement of fluids between the plasma and the interstitial space. The overall effect is filtration at the arterial end and reabsorption at the venous end (Figure 3-1). Interstitial hydrostatic pressure promotes the movement of about 10% of the interstitial fluid along with small amounts of protein into the lymphatics, which eventually returns to the circulation.
An important factor in capillary filtration of fluid is the integrity of the capillary membrane. Changes in membrane permeability may permit the escape of plasma proteins into the interstitial space. The normal relationship defined by the Starling hypothesis is altered with the osmotic movement of water into the interstitial space, causing tissue edema.
Edema is the excessive accumulation of fluid within the interstitial spaces. It is often a problem of fluid distribution and does not necessarily indicate a fluid excess. In some conditions, sequestered fluids can cause both edema and intravascular dehydration. The pathophysiologic process of edema is related to an increase in the forces favoring fluid filtration from the capillaries or lymphatic channels into the tissues. The four most common mechanisms are:
Increased capillary hydrostatic pressure can result from venous obstruction or sodium and water retention. Venous obstruction causes hydrostatic pressure to increase behind the obstruction, pushing fluid from the capillaries into the interstitial spaces. Venous blood clots, hepatic obstruction, right heart failure, tight clothing around the extremities, and prolonged standing are common causes of venous obstruction. Right congestive heart failure, renal failure, and cirrhosis of the liver are conditions associated with excessive sodium and water retention, which in turn cause volume overload, increased venous pressure, and edema.
Decreased plasma oncotic pressure results from losses or diminished production of plasma albumin. Decreased oncotic attraction of fluid within the capillary causes fluid to move into the interstitial space, resulting in edema. Decreased synthesis of plasma protein and decreased oncotic pressure may occur with liver disease or protein malnutrition. Losses of plasma proteins occur with glomerular diseases of the kidney (nephrotic syndrome), hemorrhage, and serous drainage from open wounds or burns.
Increased capillary permeability is usually associated with inflammation and the immune response. (Immunity is discussed in Chapters 7, 8, and 9; inflammation is discussed in Chapters 7 and 9.) These responses are often the result of trauma such as burns or crushing injuries, neoplastic disease, allergic reactions, and infection. Excess amounts of fluid escape from the plasma to the interstitial space and produce edema. This type of edema is often very severe because of loss of proteins from the vascular space, which decreases capillary oncotic pressure and increases interstitial oncotic pressure.
Lymphatic obstruction occurs when the lymphatic channels are blocked because of infection or tumor. Proteins and fluids are not reabsorbed and accumulate in the interstitial space, causing lymphedema. Lymphedema of the arm or leg also can occur after surgical removal of axillary or femoral lymph nodes, respectively, for treatment of cancer.3
Edema may be localized or generalized. Some localized edema is usually limited to the site of tissue injury, as in a sprained joint. Local edema can also occur within particular organs, causing, for example, cerebral edema in the brain and pulmonary edema in the lungs. Edema of specific organs, such as the brain, lung, or larynx, can be life threatening.
Generalized edema is manifested by a more uniform distribution of fluid in interstitial spaces throughout the body. Dependent edema, in which fluid accumulates in gravity-dependent areas of the body, might appear in the feet and legs when standing and in the sacral area and buttocks when supine. Dependent edema can be identified by using the fingers to press away edematous fluid in tissues overlying bony prominences. A pit will be left in the skin; hence the term pitting edema (Figure 3-3).
Edema is usually associated with swelling and puffiness, tight-fitting clothes and shoes, and limited movement of the affected area. Weight gain can be significant. The accumulation of fluid increases the distance required for nutrients, oxygen, and wastes to move between capillaries and cells in the tissues. Increased tissue pressure also may diminish capillary blood flow, leading to ischemia. Therefore, wounds heal more slowly and formation of pressure sores increases (see Chapter 46).
As edematous fluid accumulates, it is trapped in a “third space” (i.e., the interstitial space) and dehydration can develop as a result of this sequestering of fluid. Such sequestration occurs with severe burns, in which large amounts of vascular fluid are lost to the interstitial spaces, reducing plasma volume and causing shock (see Chapter 48).
Specific conditions causing edema require diagnosis. Edema may be treated symptomatically until the underlying disorder is corrected. Supportive measures include elevating edematous limbs, using compression stockings or devices, avoiding prolonged standing, restricting salt intake, and taking diuretics.
The kidneys and hormones have a central role in maintaining sodium and water balance. Because water follows the osmotic gradients established by changes in salt concentration, sodium balance and water balance are intimately related. Sodium is regulated by the renal effects of aldosterone from the adrenal cortex and natriuretic peptides from the heart. Water balance is primarily regulated by antidiuretic hormone (ADH; also known as arginine-vasopressin) from the posterior pituitary.
Sodium accounts for 90% of the ECF cations (positively charged ions). The distribution of electrolytes in body compartments is summarized in Table 3-5 and the concentration of electrolytes is summarized in Table 3-1. As the most abundant ECF cation, along with its constituent anions (negatively charged ions) chloride and bicarbonate, sodium regulates extracellular osmotic forces and therefore regulates water balance. Sodium is important in other body functions, including maintenance of neuromuscular irritability for conduction of nerve impulses (in conjunction with potassium and calcium), regulation of acid-base balance (through sodium bicarbonate and sodium phosphate), participation in cellular chemical reactions, and transport of substances across the cellular membrane (see Chapter 1).
|EXTRACELLULAR FLUID (mEq/L)||INTRACELLULAR FLUID (mEq/L)|
The kidney, in conjunction with neural and hormonal mediators, maintains normal serum sodium concentration within a narrow range (135 to 145 mEq/L) primarily through renal tubular reabsorption. The average dietary intake of sodium ranges from 5 to 6 g/day; the minimal daily requirement of sodium is 500 mg. Sweating depletes sodium and water volume and increases the body’s sodium requirement.
Hormonal regulation of sodium balance is mediated by aldosterone, a mineralocorticoid (steroid) synthesized and secreted from the adrenal cortex as the end product of the renin-angiotensin-aldosterone system (Figure 3-4) (also see Chapters 21 and 37). When circulating blood pressure and renal blood flow, or serum sodium concentrations, are reduced, renin, an enzyme secreted by the juxtaglomerular cells of the kidney, is released. Renin stimulates the formation of angiotensin I, an inactive polypeptide. Angiotensin-converting enzyme (ACE) in pulmonary vessels converts angiotensin I to angiotensin II. Angiotensin II has two major functions: it causes vasoconstriction, which elevates systemic blood pressure, and it stimulates the secretion of aldosterone. Aldosterone promotes sodium and water reabsorption by the proximal tubules of the kidneys, thus conserving sodium, blood volume, and blood pressure. Aldosterone also stimulates secretion (and therefore excretion) of potassium by the distal tubule of the kidney, reducing potassium concentrations in the ECF. The restoration of sodium levels, blood volume, and renal perfusion then inhibits further release of renin.
Natriuretic peptides are hormones that include atrial natriuretic peptide (ANP) produced by myoendocrine atrial cells, brain natriuretic peptide (BNP—named brain since it was first discovered in porcine brain) produced by myoendocrine ventricular cells, and urodilatin (an ANP analog) synthesized within the kidney. ANP and BNP are released when there is an increase in transmural atrial pressure caused by increased intra-atrial volume as may occur with heart failure.4 ANP and BNP increase sodium and water excretion by the kidneys, which lowers blood volume and pressure. Urodilatin is released from distal tubular kidney cells when there is increased arterial pressure and increased renal blood flow. These hormones are natural antagonists to the renin-angiotensin-aldosterone system. The restoration of lower atrial pressure then inhibits further release of ANP and BNP.
Chloride is the major anion in the ECF and provides electroneutrality, particularly in relation to sodium. Chloride transport is generally passive and follows the active transport of sodium so that increases or decreases in chloride are proportional to changes in sodium. Chloride concentration tends to vary inversely with changes in the concentration of bicarbonate (), the other major ECF anion.
One manner by which water balance is regulated is through the perception of thirst. Thirst is a sensation that stimulates water-drinking behavior. Thirst is experienced when water loss equals 2% of an individual’s body weight or when there is an increase in osmolality. Dry mouth, hyperosmolality, and plasma volume depletion activate hypothalamic osmoreceptors. The action of the osmoreceptors then causes thirst. Drinking water restores plasma volume and dilutes the ECF osmolality.
Water balance also is directly regulated by antidiuretic hormone (arginine-vasopressin), which is secreted when plasma osmolality increases or circulating blood volume decreases and blood pressure drops (Figure 3-5). Increased plasma osmolality occurs with a water deficit or sodium excess in relation to water. The increased osmolality stimulates hypothalamic osmoreceptors. In addition to causing thirst, the stimulated osmoreceptors signal the posterior pituitary to release ADH. The action of ADH is to increase the permeability of renal tubular cells to water, increasing water reabsorption and promoting the restoration of plasma volume and blood pressure. Urine concentration increases, and the reabsorbed water decreases plasma osmolality, returning it toward normal. Like most hormones, ADH is regulated by a feedback mechanism. The restoration of plasma osmolality, blood volume, and blood pressure then inhibits ADH secretion.
With fluid loss (dehydration) (e.g., from vomiting, diarrhea, or excessive sweating), a decrease in blood volume and blood pressure often occurs. Baroreceptors (volume/pressure sensitive receptors) (stretch receptors that are sensitive to changes in arterial volume and pressure) also stimulate the release of ADH. Baroreceptors are located in the right and left atria and large veins, and in the aorta, pulmonary arteries, and carotid sinus. When arterial and atrial pressure drops baroreceptors signal the hypothalamus to release ADH. The reabsorption of water mediated by ADH then promotes the restoration of plasma volume and blood pressure (see Figure 3-5). ADH also stimulates arterial vasoconstriction.
Alterations in sodium and water balance are closely related. Water imbalances may develop because of changes in osmotic gradients caused by gain or loss of salt. Likewise, sodium imbalances occur with alterations in body water volume. Generally the alterations can be classified as changes in tonicity, or the change in concentration of electrolytes in relation to water (see Chapter 1). Alterations can therefore be classified as isotonic, hypertonic, or hypotonic (Table 3-6 and Figure 3-6).
|Isotonic (isoosmolar) imbalance||Gain or loss of extracellular fluid (ECF) resulting in a concentration equivalent to a 0.9% sodium chloride (salt) solution (normal saline); no shrinking or swelling of cells|
|Hypertonic (hyperosmolar) imbalance||Imbalance that results in an ECF concentration >0.9% salt solution; that is, water loss or solute gain; cells shrink in a hypertonic fluid|
|Hypotonic (hypoosmolar) imbalance||Imbalance that results in an ECF <0.9% salt solution; that is, water gain or solute loss; cells swell in a hypotonic fluid|
The term isotonic refers to a solution that has the same concentration of solutes as the plasma. Isotonic alterations occur when changes in TBW are accompanied by proportional changes in the amounts of electrolytes and water. For example, if an individual loses pure plasma or ECF, fluid volume is depleted but the number and type of electrolytes (e.g., sodium) and the osmolality remain within a normal range. Excessive amounts of isotonic body fluids can result from excessive administration of intravenous normal saline (0.9% NaCl) or oversecretion of aldosterone with renal retention of both sodium and water. Isotonic fluid loss results in hypovolemia. Causes include hemorrhage, severe wound drainage, and excessive diaphoresis (sweating). Loss of extracellular volume results in weight loss, dryness of skin and mucous membranes, decreased urine output, increased hematocrit value, and symptoms of hypovolemia. Indicators of hypovolemia include a rapid heart rate and flattened neck veins, and can present with a normal or decreased blood pressure. In severe states, hypovolemic shock (severe hypotension) can occur (see Chapter 48).
Isotonic fluid excesses result in hypervolemia. Causes include excessive administration of intravenous fluids, hypersecretion of aldosterone, the effects of drugs such as cortisone, or renal failure. Weight gain and a decrease in hematocrit level and plasma protein concentration caused by the diluting effect of excess plasma volume will occur. The neck veins may distend, and the blood pressure increases. Increased capillary hydrostatic pressure leads to edema formation. If the plasma volume is great enough, pulmonary edema and heart failure develop.
Hypertonic fluid alterations develop when the osmolality of the ECF is elevated above normal (greater than 294 mOsm). The most common causes are an increased concentration of ECF sodium (hypernatremia) or a deficit of ECF free water. In both instances the hypertonicity of the ECF attracts water from the intracellular space, causing ICF dehydration. A primary increase in the amount of ECF sodium causes an osmotic attraction of water and symptoms of hypervolemia. In contrast, a hypertonic state caused primarily by free water loss leads to hypovolemia (Table 3-7).
|CAUSATIVE FACTOR||MECHANISM||ECF EFFECTS||ICF EFFECTS|
|Increased sodium (hypernatremia)||Excessive hypertonic salt solutions|
Intravenous hypertonic sodium
Selected infant formulas
Increased blood pressure
Decreased urine output
Shrinkage of brain cells
|Water deficit||Water deprivation|
Confusion or coma
Inability to communicate
Loss of thirst
|Other factors||Hyperglycemia||Initial dilutional hyponatremia|
Hypernatremia occurs when serum sodium levels exceed 147 mEq/L. Increased serum sodium concentration may be caused by loss of water (most common) or an acute gain in sodium. With water loss, both ICF dehydration and ECF dehydration occur. Hyperosmolality is a common result of hypernatremia. Because sodium is largely in the ECF, increases in the concentration of sodium cause intracellular dehydration and hypervolemia (see Table 3-7 and Figure 3-6, C).
Increased sodium concentration caused by water deprivation or water loss is associated with fever or respiratory tract infections, which increase the respiratory rate and enhance water loss from the lungs. Diabetes insipidus (deficiency of ADH), polyuria (frequent urination), profuse sweating, and diarrhea cause water loss in relation to sodium concentration. Infants with severe diarrhea are particularly vulnerable. Insufficient water intake also can cause hypernatremia (e.g., individuals who are immobilized or receiving gastric feedings, those who are comatose or confused, or infants because they cannot communicate thirst).
Increased sodium retention occurs because of (1) inappropriate administration of hypertonic saline solution (e.g., as sodium bicarbonate for treatment of acidosis during cardiac arrest); (2) oversecretion of aldosterone (as in primary hyperaldosteronism), where sodium reabsorption exceeds water reabsorption; or (3) Cushing syndrome (caused by excess secretion of adrenocorticotropic hormone [ACTH], which also causes increased secretion of aldosterone). High amounts of dietary sodium rarely cause hypernatremia in a healthy individual because the sodium is eliminated by the kidneys. However, increased amounts of dietary sodium (greater than 5 grams per day) is associated with cardiovascular disease (see Chapter 32).
Water is redistributed to the extracellular space, and intracellular dehydration ensues. Thirst, fever, dry mucous membranes, hypotension, tachycardia, low jugular venous pressure, and restlessness are associated with hypernatremia as a result of water loss. Pulmonary edema occurs when water shifts from the ICF to the interstitial space. Central nervous system symptoms are the most serious and are related to alterations in membrane potentials and shrinking of brain cells. Symptoms include muscle twitching and hyperreflexia (hyperactive reflexes), confusion, coma, convulsions, and cerebral hemorrhage from stretching of veins.
The serum sodium level is usually more than 147 mEq/L. If there is water loss, urine specific gravity will be greater than 1.030 and the levels of hematocrit and plasma proteins will be elevated. The treatment of hypernatremia is to give an isotonic salt-free fluid (5% dextrose in water) until the serum sodium level returns to normal.5 Fluid replacement must be given slowly to prevent cerebral edema and serum sodium levels need to be closely monitored. Hypervolemia and hypovolemia require treatment of the underlying clinical condition.
Because chloride follows sodium, hyperchloremia (elevation of serum chloride concentration greater than 105 mEq/L) often accompanies hypernatremia, as well as plasma bicarbonate deficits, as in hyperchloremic metabolic acidosis (see p. 126). There are no specific symptoms or treatment for chloride excess and treatment is related to management of the underlying disorder.
Dehydration refers to water deficit, but also is commonly used to indicate both sodium and water loss (isotonic or isoosmolar dehydration). Pure water deficits (hyperosmolar or hypertonic dehydration) are rare because most people have access to water. Individuals who are comatose or paralyzed continue insensible water losses through the skin and lungs with a minimal obligatory formation of urine. Hyperventilation caused by fever also may precipitate water deficit. The most common cause of water loss is increased renal clearance of free water as a result of impaired tubular function or inability to concentrate the urine, as with diabetes insipidus (decreased or absent ADH) (see Table 3-7 and Chapter 22).
Marked water deficit is manifested by symptoms of dehydration: headache, thirst, dry skin and mucous membranes, weight loss, decreased urine output, and concentrated urine (with the exception of diabetes insipidus). Skin turgor may be normal or decreased. Symptoms of hypovolemia, including tachycardia, weak pulses, and postural hypotension, may be present.
Treatment is to give water and stop fluid loss. Fluid replacement must be given slowly enough to prevent rapid movement of water into brain cells, which causes cerebral edema, seizures, brain injury, and death. When intravenous replacement is required, hypotonic saline solutions or 5% dextrose in water is used because pure water lyses red blood cells.
Hypotonic fluid imbalances occur when the osmolality of the ECF is less than normal (less than 280 mOsm). The most common causes are sodium deficit (hyponatremia) or free water excess (water intoxication). Both causes lead to an intracellular overhydration (cellular edema) and cell swelling when water moves into the cell, where the osmotic pressure is greater (see Figure 3-6, A). Cerebral and pulmonary edema occur in conjunction with these fluid shifts.6 With hyponatremia, the plasma volume then decreases, leading to symptoms of hypovolemia. With free water excess, the ECF volume is elevated, causing symptoms of hypervolemia (Table 3-8).
|CAUSATIVE FACTOR||MECHANISM||ECF EFFECTS||ICF EFFECTS|
|Decreased sodium (hyponatremia)||Inadequate intake|
Excessive diuretic therapy
|Extracellular volume contraction and hypovolemia (but may not if there is water excess)||Increased intracellular water; edema|
Brain cell swelling, irritability, depression, confusion
Systemic cellular edema, including weakness, anorexia, nausea, and diarrhea
|Water excess||Excessive pure water intake|
Excessive administration of hypotonic intravenous solutions
Drinking water to replace isotonic fluid losses
Tap water enemas
Renal water retention
Syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
|Extracellular volume expands with hypervolemia (but may not if fluid is trapped in intracellular space)||Edema (see above)|
|Other factors||Isotonic dehydration treated with intravenous D5W; glucose in D5W solution is metabolized to water, contributing to hyponatremia|
|Hypervolemia or hypovolemia||Edema (see above)|
Hyponatremia develops when the serum sodium concentration decreases to less than 135 mEq/L. It is the most common electrolyte disorder in hospitalized individuals.7 Hyponatremia may be caused by sodium loss, inadequate sodium intake, or dilution of the body’s sodium level. Clinical syndromes that may cause hyponatremia include syndrome of inappropriate secretion of antidiuretic hormone (SIADH, excess ADH) or failure of the distal tubules to reabsorb sodium. Sodium deficits usually cause hypoosmolality and water moves into cells, resulting in cell swelling (see Figure 3-6, A, and What’s New? Hyponatremia and Hospitalization).
Pure sodium deficits are usually caused by diuretics8 and extrarenal losses such as vomiting, diarrhea, gastrointestinal suctioning, or burns. Inadequate intake of dietary sodium is rare but can occur in individuals consuming low-sodium diets, particularly among those taking diuretics. Dilutional hyponatremias occur when there is an excess of TBW in relation to total body sodium or a shift of water from the ICF to the ECF space (e.g., administration of mannitol). Replacement of fluid loss with intravenous 5% dextrose in water also can cause a dilutional hyponatremia because once the glucose is metabolized, a hypotonic solution remains with a diluting effect. Use of excess hypotonic saline (e.g., 0.45% NaCl) may also result in dilution. In addition, excessive sweating may stimulate thirst and intake of large amounts of water, which dilute sodium; this condition may be associated with endurance exercise in which there is only pure water replacement.
Hyponatremia may cause hypotonic or hypertonic alterations. During acute oliguric renal failure, severe congestive heart failure, or cirrhosis, renal excretion of water is impaired. Both TBW and sodium levels are increased, but TBW level exceeds the increase in sodium level, producing a hypotonic hyponatremia. Hypertonic hyponatremia develops with the shift of water from the ICF to the ECF as occurs with hyperglycemia, hyperlipidemia, and hyperproteinemia. The osmotic fluid shift to the ECF in turn dilutes the concentration of sodium and other electrolytes.
Cellular swelling and deficits of intracellular sodium alter the ability of cells to depolarize and repolarize normally (see Chapter 1). Neurologic changes characteristic of hyponatremia include lethargy, headache, confusion, apprehension, seizures, and coma. Pure sodium losses may be accompanied by loss of ECF, causing hypovolemia with symptoms of hypotension, tachycardia, and decreased urine output. Dilutional hyponatremia is accompanied by weight gain, edema, ascites, and jugular vein distention. Cerebral edema can be a life-threatening complication of hypervolemic hyponatremia caused by increases in intracranial pressure.
In hyponatremic states, serum sodium concentration falls to less than 135 mEq/L. With pure sodium deficits, the hematocrit and plasma protein levels may be elevated. Urine specific gravity is less than 1.010 when renal function is normal because sodium is maximally conserved.
Treatment of hyponatremia is related to the contributing disorder. Losses of sodium and water volume are calculated from the clinical evaluation, and appropriate solutions then are selected for replacement. Restriction of water intake is required in most cases of dilutional hyponatremia because body sodium levels may be normal or increased even though serum concentrations are low. Hypertonic saline solutions are used cautiously with severe hyponatremia or the presence of symptoms such as seizures.9
Hypochloremia, a low level of serum chloride (less than 97 mEq/L), usually occurs with hyponatremia or an elevated bicarbonate concentration, as in metabolic alkalosis (see p. 128). Sodium deficit related to restricted intake, use of diuretics, and vomiting are accompanied by chloride deficiency. Cystic fibrosis is a genetic disease characterized by hypochloremia (see Chapters 36 and 42). In all cases, treatment of the underlying cause is required.
When the body is functioning normally, it is almost impossible to produce an excess of TBW since water balance is regulated by the kidneys. However, some individuals with psychogenic disorders develop water intoxication from compulsive water drinking. Intensive exercise with replacement of large volumes of electrolyte-free water also causes overhydration. Acute renal failure, severe congestive heart failure, and cirrhosis are clinical conditions that can precipitate water excess. Decreased urine formation from renal disease or decreased renal blood flow contributes to water excess. The overall effect is dilution of the ECF with the movement of water to the intracellular space by osmosis. The syndrome of inappropriate secretion of ADH (SIADH), also known as vasopressin dysregulation, enhances water retention because ADH levels are elevated (see Chapter 22, p. 718). Water excess is usually accompanied by hyponatremia.
Serum sodium concentration can be decreased, but this also can occur with a pure sodium deficit. Serum and urine osmolalities are decreased because water concentration will be in excess of sodium concentration. Urine sodium concentration will be reduced. The hematocrit value is reduced from the dilutional effect of water excess.
Fluid restriction for 24 hours is an effective treatment if there are no severe neurologic symptoms or convulsions. Small amounts of intravenous hypertonic sodium chloride (i.e., 3% sodium chloride) can be given when neurologic symptoms are severe.
Potassium (K+) is the major intracellular electrolyte and is found in most body fluids (see Table 3-5, p. 108). The ICF concentration of K+ is 150 to 160 mEq/L; the ECF concentration is 3.5 to 5.0 mEq/L. Total body potassium content is about 4000 mEq, with most of it located in the cells. Daily dietary intake of potassium is 40 to 150 mEq/day, with an average of 1.5 mEq/kg body weight.
Potassium balance is maintained by renal excretion of K+ absorbed from the gastrointestinal tract. Absorbed dietary K+ moves rapidly into cells. However, the distribution of K+ between intracellular and extracellular fluids can fluctuate and is influenced by several factors. Aldosterone, insulin, epinephrine (β-adrenergic stimulation), and alkalosis facilitate the shift of K+ into cells. Insulin deficiency, aldosterone deficiency, acidosis, and strenuous exercise facilitate the shift of K+ out of cells. α-Adrenergics impair K+ entry into cells. Glucagon blocks entry of K+ into cells, and glucocorticoids promote K+ excretion. Potassium also will move out of cells along with water when there is increased ECF osmolarity (number of osmoles of solute per liter of fluid). If cells lyse, they release their intracellular K+ into the ECF, which can cause an acute rise in plasma K+ levels.
Besides acting to conserve sodium, aldosterone is a major factor in potassium regulation. Elevated plasma K+ concentration causes adrenal secretion of aldosterone. Aldosterone then stimulates the release of K+ into the urine by the distal renal tubules.
Insulin contributes to the regulation of plasma potassium levels by stimulating the Na+-K+-ATPase pump, thereby promoting the movement of K+ into liver and muscle cells simultaneously with glucose transport. The intracellular movement of K+ prevents an acute hyperkalemia related to food intake. Insulin also can be used to treat hyperkalemia. However, dangerously low levels of plasma K+ can result from the administration of insulin when K+ levels are depressed. Potassium balance is especially significant in the treatment of conditions requiring insulin administration, such as insulin-dependent diabetes mellitus (type 1).
The difference in the K+ intracellular to extracellular concentration is maintained by a sodium-potassium active transport system (Na+-K+-ATPase pump). The ratio of ICF K+ concentration to ECF K+ concentration is the major determinant of the resting membrane potential, which is necessary for the transmission and conduction of nervous impulses, maintenance of normal cardiac rhythms, and contraction of skeletal and smooth muscles (see Figure 1-35, p. 35). The constant diffusion of positively charged K+ out of the cell (i.e., down its concentration gradient) makes the interior of cells electronegative in relation to the ECF. Changes in the ratio of ICF to ECF potassium are responsible for many of the symptoms associated with K+ imbalance.
As the predominant ICF ion, K+ exerts a major influence on the regulation of ICF osmolality and fluid balance, as well as on intracellular electrical neutrality in relation to hydrogen (H+) and Na+ levels. Potassium is also necessary for a variety of metabolic functions and is required for glycogen deposition in liver and skeletal muscle cells.
The kidney provides the most efficient regulation of K+ level balance over time. The amount of K+ excreted varies in proportion to the dietary intake (40 to 120 mEq/day). Potassium is freely filtered by the renal glomerulus, and 90% is reabsorbed by the proximal tubule and loop of Henle. Principal cells in the collecting duct secrete K+ and intercalated cells in the collecting duct reabsorb K+. Dietary K+ intake, aldosterone level, and distal tubule urine flow determine the amount of K+ excreted from the body. Unlike sodium, the renal mechanism for conserving K+ is weak, even when total body K+ stores are depleted. The gut also may sense the amount of K+ ingested and stimulate renal K+ excretion.10 However, a low K+ intake also suppresses renal K+ excretion.