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Normal Exchange of Fluid and Electrolytes
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The healthy person consumes an average of 2000 mL of water per day, approximately 75% from oral intake and the rest extracted from solid foods. Daily water losses include 800 to 1200 mL in urine, 250 mL in stool, and 600 mL in insensible losses. Insensible losses of water occur through both the skin (75%) and lungs (25%) and can be increased by such factors as fever, hypermetabolism, and hyperventilation. Sensible water losses such as sweating or pathologic loss of gastrointestinal (GI) fluids vary widely, but these include the loss of electrolytes as well as water (Table 3-1). To clear the products of metabolism, the kidneys must excrete a minimum of 500 to 800 mL of urine per day, regardless of the amount of oral intake.
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The typical individual consumes 3 to 5 g of dietary salt per day, with the balance maintained by the kidneys. With hyponatremia or hypovolemia, sodium excretion can be reduced to as little as 1 mEq/d or maximized to as much as 5000 mEq/d to achieve balance except in people with salt-wasting kidneys. Sweat is hypotonic, and sweating usually results in only a small sodium loss. GI losses are isotonic to slightly hypotonic and contribute little to net gain or loss of free water when measured and appropriately replaced by isotonic salt solutions.
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Classification of Body Fluid Changes
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Disorders in fluid balance may be classified into three general categories: disturbances in (a) volume, (b) concentration, and (c) composition. Although each of these may occur simultaneously, each is a separate entity with unique mechanisms demanding individual correction. Isotonic gain or loss of salt solution results in extracellular volume changes, with little impact on intracellular fluid volume. If free water is added or lost from the ECF, water will pass between the ECF and intracellular fluid until solute concentration or osmolarity is equalized between the compartments. Unlike with sodium, the concentration of most other ions in the ECF can be altered without significant change in the total number of osmotically active particles, producing only a compositional change. For instance, doubling the serum potassium concentration will profoundly alter myocardial function without significantly altering volume or concentration of the fluid spaces.
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Disturbances in Fluid Balance
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Extracellular volume deficit is the most common fluid disorder in surgical patients and can be either acute or chronic. Acute volume deficit is associated with cardiovascular and central nervous system signs, whereas chronic deficits display tissue signs, such as a decrease in skin turgor and sunken eyes, in addition to cardiovascular and central nervous system signs (Table 3-2).Laboratory examination may reveal an elevated blood urea nitrogen level if the deficit is severe enough to reduce glomerular filtration and hemoconcentration. Urine osmolality usually will be higher than serum osmolality, and urine sodium will be low, typically <20 mEq/L. Serum sodium concentration does not necessarily reflect volume status and therefore may be high, normal, or low when a volume deficit is present. The most common cause of volume deficit in surgical patients is a loss of GI fluids (Table 3-3) from nasogastric suction, vomiting, diarrhea, or enterocutaneous fistula. In addition, sequestration secondary to soft tissue injuries, burns, and intra-abdominal processes such as peritonitis, obstruction, or prolonged surgery can also lead to massive volume deficits.
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Extracellular volume excess may be iatrogenic or secondary to renal dysfunction, congestive heart failure, or cirrhosis. Both plasma and interstitial volumes usually are increased. Symptoms are primarily pulmonary and cardiovascular (see Table 3-2). In fit patients, edema and hyperdynamic circulation are common and well tolerated. However, the elderly and patients with cardiac disease may quickly develop congestive heart failure and pulmonary edema in response to only a moderate volume excess.
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Volume changes are sensed by both osmoreceptors and baroreceptors. Osmoreceptors are specialized sensors that detect even small changes in fluid osmolality and drive changes in thirst and diuresis through the kidneys.2 For example, when plasma osmolality is increased, thirst is stimulated and water consumption increases, although the exact cell mechanism is not known.3 Additionally, the hypothalamus is stimulated to secrete vasopressin, which increases water reabsorption in the kidneys. Together, these two mechanisms return the plasma osmolality to normal. Baroreceptors also modulate volume in response to changes in pressure and circulating volume through specialized pressure sensors located in the aortic arch and carotid sinuses.4 Baroreceptor responses are both neural, through sympathetic and parasympathetic pathways, and hormonal, through substances including renin-angiotensin, aldosterone, atrial natriuretic peptide, and renal prostaglandins. The net result of alterations in renal sodium excretion and free water reabsorption is restoration of volume to the normal state.
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Concentration Changes
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Changes in serum sodium concentration are inversely proportional to TBW. Therefore, abnormalities in TBW are reflected by abnormalities in serum sodium levels.
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A low serum sodium level occurs when there is an excess of extracellular water relative to sodium. Extracellular volume can be high, normal, or low (Fig. 3-3). In most cases of hyponatremia, sodium concentration is decreased as a consequence of either sodium depletion or dilution.5 Dilutional hyponatremia frequently results from excess extracellular water and therefore is associated with a high extracellular volume status. Excessive oral water intake or iatrogenic intravenous (IV) excess free water administration can cause hyponatremia. Postoperative patients are particularly prone to increased secretion of antidiuretic hormone (ADH), which increases reabsorption of free water from the kidneys with subsequent volume expansion and hyponatremia. This is usually self-limiting in that both hyponatremia and volume expansion decrease ADH secretion. Additionally, a number of drugs can cause water retention and subsequent hyponatremia, such as the antipsychotics and tricyclic antidepressants as well as angiotensin-converting enzyme inhibitors. The elderly are particularly susceptible to drug-induced hyponatremia. Physical signs of volume overload usually are absent, and laboratory evaluation reveals hemodilution. Depletional causes of hyponatremia are associated with either a decreased intake or increased loss of sodium-containing fluids. A concomitant ECF volume deficit is common. Causes include decreased sodium intake, such as consumption of a low-sodium diet or use of enteral feeds, which are typically low in sodium; GI losses from vomiting, prolonged nasogastric suctioning, or diarrhea; and renal losses due to diuretic use or primary renal disease.
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Hyponatremia also can be seen with an excess of solute relative to free water, such as with untreated hyperglycemia or mannitol administration. Glucose exerts an osmotic force in the extracellular compartment, causing a shift of water from the intracellular to the extracellular space. Hyponatremia therefore can be seen when the effective osmotic pressure of the extracellular compartment is normal or even high. When hyponatremia in the presence of hyperglycemia is being evaluated, the corrected sodium concentration should be calculated as follows:
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For every 100-mg/dL increment in plasma glucose above normal, the plasma sodium should decrease by 1.6 mEq/L
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Lastly, extreme elevations in plasma lipids and proteins can cause pseudohyponatremia, because there is no true decrease in extracellular sodium relative to water.
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Signs and symptoms of hyponatremia (Table 3-4) are dependent on the degree of hyponatremia and the rapidity with which it occurred. Clinical manifestations primarily have a central nervous system origin and are related to cellular water intoxication and associated increases in intracranial pressure. Oliguric renal failure also can be a rapid complication in the setting of severe hyponatremia.
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A systematic review of the etiology of hyponatremia should reveal its cause in a given instance. Hyperosmolar causes, including hyperglycemia or mannitol infusion and pseudohyponatremia, should be easily excluded. Next, depletional versus dilutional causes of hyponatremia are evaluated. In the absence of renal disease, depletion is associated with low urine sodium levels (<20 mEq/L), whereas renal sodium wasting shows high urine sodium levels (>20 mEq/L). Dilutional causes of hyponatremia usually are associated with hypervolemic circulation. A normal volume status in the setting of hyponatremia should prompt an evaluation for a syndrome of inappropriate secretion of ADH.
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Hypernatremia results from either a loss of free water or a gain of sodium in excess of water. Like hyponatremia, it can be associated with an increased, normal, or decreased extracellular volume (see Fig. 3-3). Hypervolemic hypernatremia usually is caused either by iatrogenic administration of sodium-containing fluids, including sodium bicarbonate, or mineralocorticoid excess as seen in hyperaldosteronism, Cushing’s syndrome, and congenital adrenal hyperplasia. Urine sodium concentration is typically >20 mEq/L, and urine osmolarity is >300 mOsm/L. Normovolemic hypernatremia can result from renal causes, including diabetes insipidus, diuretic use, and renal disease, or from nonrenal water loss from the GI tract or skin, although the same conditions can result in hypovolemic hypernatremia. When hypovolemia is present, the urine sodium concentration is <20 mEq/L and urine osmolarity is <300 to 400 mOsm/L. Nonrenal water loss can occur secondary to relatively isotonic GI fluid losses such as that caused by diarrhea, to hypotonic skin fluid losses such as loss due to fever, or to losses via tracheotomies during hyperventilation. Additionally, thyrotoxicosis can cause water loss, as can the use of hypertonic glucose solutions for peritoneal dialysis. With nonrenal water loss, the urine sodium concentration is <15 mEq/L and the urine osmolarity is >400 mOsm/L.
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Symptomatic hypernatremia usually occurs only in patients with impaired thirst or restricted access to fluid, because thirst will result in increased water intake. Symptoms are rare until the serum sodium concentration exceeds 160 mEq/L but, once present, are associated with significant morbidity and mortality. Because symptoms are related to hyperosmolarity, central nervous system effects predominate (see Table 3-4). Water shifts from the intracellular to the extracellular space in response to a hyperosmolar extracellular space, which results in cellular dehydration. This can put traction on the cerebral vessels and lead to subarachnoid hemorrhage. Central nervous system symptoms can range from restlessness and irritability to seizures, coma, and death. The classic signs of hypovolemic hypernatremia, (tachycardia, orthostasis, and hypotension) may be present, as well as the unique findings of dry, sticky mucous membranes.
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Composition Changes: Etiology and Diagnosis
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Potassium Abnormalities
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The average dietary intake of potassium is approximately 50 to 100 mEq/d, which in the absence of hypokalemia is excreted primarily in the urine. Extracellular potassium is maintained within a narrow range, principally by renal excretion of potassium, which can range from 10 to 700 mEq/d. Although only 2% of the total body potassium (4.5 mEq/L × 14 L = 63 mEq) is located within the extracellular compartment, this small amount is critical to cardiac and neuromuscular function; thus, even minor changes can have major effects on cardiac activity. The intracellular and extracellular distribution of potassium is influenced by a number of factors, including surgical stress, injury, acidosis, and tissue catabolism.
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Hyperkalemia is defined as a serum potassium concentration above the normal range of 3.5 to 5.0 mEq/L. It is caused by excessive potassium intake, increased release of potassium from cells, or impaired potassium excretion by the kidneys (Table 3-5).6 Increased intake can be either from oral or IV supplementation, or from red cell lysis after transfusion. Hemolysis, rhabdomyolysis, and crush injuries can disrupt cell membranes and release intracellular potassium into the ECF. Acidosis and a rapid rise in extracellular osmolality from hyperglycemia or IV mannitol can raise serum potassium levels by causing a shift of potassium ions to the extracellular compartment.7 Because 98% of total body potassium is in the intracellular fluid compartment, even small shifts of intracellular potassium out of the intracellular fluid compartment can lead to a significant rise in extracellular potassium. A number of medications can contribute to hyperkalemia, particularly in the presence of renal insufficiency, including potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, and nonsteroidal anti-inflammatory drugs (NSAIDs). Spironolactone and angiotensin-converting enzyme inhibitors interfere with aldosterone activity, inhibiting the normal renal mechanism of potassium excretion. Acute and chronic renal insufficiency also impairs potassium excretion.
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Symptoms of hyperkalemia are primarily GI, neuromuscular, and cardiovascular (Table 3-6). GI symptoms include nausea, vomiting, intestinal colic, and diarrhea. Neuromuscular symptoms range from weakness to ascending paralysis to respiratory failure. Early cardiovascular signs may be apparent from electrocardiogram (ECG) changes and eventually lead to hemodynamic symptoms of arrhythmia and cardiac arrest. ECG changes that may be seen with hyperkalemia include high peaked T waves (early), widened QRS complex, flattened P wave, prolonged PR interval (first-degree block), sine wave formation, and ventricular fibrillation.
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Hypokalemia is much more common than hyperkalemia in the surgical patient. It may be caused by inadequate potassium intake; excessive renal potassium excretion; potassium loss in pathologic GI secretions, such as with diarrhea, fistulas, vomiting, or high nasogastric output; or intracellular shifts from metabolic alkalosis or insulin therapy (see Table 3-5). The change in potassium associated with alkalosis can be calculated by the following formula:
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Potassium decreases by 0.3 mEq/L for every 0.1 increase in pH above normal.
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Additionally, drugs such as amphotericin, aminoglycosides, cisplatin, and ifosfamide that induce magnesium depletion cause renal potassium wastage.8,9 In cases in which potassium deficiency is due to magnesium depletion,10 potassium repletion is difficult unless hypomagnesemia is first corrected.
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The symptoms of hypokalemia (see Table 3-6), like those of hyperkalemia, are primarily related to failure of normal contractility of GI smooth muscle, skeletal muscle, and cardiac muscle. Findings may include ileus, constipation, weakness, fatigue, diminished tendon reflexes, paralysis, and cardiac arrest. In the setting of ECF depletion, symptoms may be masked initially and then worsened by further dilution during volume repletion. ECG changes suggestive of hypokalemia include U waves, T-wave flattening, ST-segment changes, and arrhythmias (with digitalis therapy).
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Calcium Abnormalities
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The vast majority of the body’s calcium is contained within the bone matrix, with <1% found in the ECF. Serum calcium is distributed among three forms: protein found (40%), complexed to phosphate and other anions (10%), and ionized (50%). It is the ionized fraction that is responsible for neuromuscular stability and can be measured directly. When total serum calcium levels are measured, the albumin concentration must be taken into consideration:
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Adjust total serum calcium down by 0.8 mg/dL for every 1 g/dL decrease in albumin.
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Unlike changes in albumin, changes in pH will affect the ionized calcium concentration. Acidosis decreases protein binding, thereby increasing the ionized fraction of calcium.
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Daily calcium intake is 1 to 3 g/d. Most of this is excreted via the bowel, with urinary excretion relatively low. Total body calcium balance is under complex hormonal control, but disturbances in metabolism are relatively long term and less important in the acute surgical setting. However, attention to the critical role of ionized calcium in neuromuscular function often is required.
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Hypercalcemia is defined as a serum calcium level above the normal range of 8.5 to 10.5 mEq/L or an increase in the ionized calcium level above 4.2 to 4.8 mg/dL. Primary hyperparathyroidism in the outpatient setting and malignancy in hospitalized patients, from either bony metastasis or secretion of parathyroid hormone–related protein, account for most cases of symptomatic hypercalcemia.11 Symptoms of hypercalcemia (see Table 3-6), which vary with the degree of severity, include neurologic impairment, musculoskeletal weakness and pain, renal dysfunction, and GI symptoms of nausea, vomiting, and abdominal pain. Cardiac symptoms can be manifest as hypertension, cardiac arrhythmias, and a worsening of digitalis toxicity. ECG changes in hypercalcemia include shortened QT interval, prolonged PR and QRS intervals, increased QRS voltage, T-wave flattening and widening, and atrioventricular block (which can progress to complete heart block and cardiac arrest).
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Hypocalcemia is defined as a serum calcium level below 8.5 mEq/L or a decrease in the ionized calcium level below 4.2 mg/dL. The causes of hypocalcemia include pancreatitis, massive soft tissue infections such as necrotizing fasciitis, renal failure, pancreatic and small bowel fistulas, hypoparathyroidism, toxic shock syndrome, abnormalities in magnesium levels, and tumor lysis syndrome. In addition, transient hypocalcemia commonly occurs after removal of a parathyroid adenoma due to atrophy of the remaining glands and avid bone remineralization, and sometimes requires high-dose calcium supplementation.12 Additionally, malignancies associated with increased osteoblastic activity, such as breast and prostate cancer, can lead to hypocalcemia from increased bone formation.13 Calcium precipitation with organic anions is also a cause of hypocalcemia and may occur during hyperphosphatemia from tumor lysis syndrome or rhabdomyolysis. Pancreatitis may sequester calcium via chelation with free fatty acids. Massive blood transfusion with citrate binding is another mechanism.14,15 Hypocalcemia rarely results solely from decreased intake, because bone reabsorption can maintain normal levels for prolonged periods.
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Asymptomatic hypocalcemia may occur when hypoproteinemia results in a normal ionized calcium level. Conversely, symptoms can develop with a normal serum calcium level during alkalosis, which decreases ionized calcium. In general, neuromuscular and cardiac symptoms do not occur until the ionized fraction falls below 2.5 mg/dL (see Table 3-6). Clinical findings may include paresthesias of the face and extremities, muscle cramps, carpopedal spasm, stridor, tetany, and seizures. Patients will demonstrate hyperreflexia and may exhibit positive Chvostek’s sign (spasm resulting from tapping over the facial nerve) and Trousseau’s sign (spasm resulting from pressure applied to the nerves and vessels of the upper extremity with a blood pressure cuff). Hypocalcemia may lead to decreased cardiac contractility and heart failure. ECG changes of hypocalcemia include prolonged QT interval, T-wave inversion, heart block, and ventricular fibrillation.
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Phosphorus Abnormalities
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Phosphorus is the primary intracellular divalent anion and is abundant in metabolically active cells. Phosphorus is involved in energy production during glycolysis and is found in high-energy phosphate products such as adenosine triphosphate. Serum phosphate levels are tightly controlled by renal excretion.
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Hyperphosphatemia can be due to decreased urinary excretion, increased intake, or endogenous mobilization of phosphorus. Most cases of hyperphosphatemia are seen in patients with impaired renal function. Hypoparathyroidism or hyperthyroidism also can decrease urinary excretion of phosphorus and thus lead to hyperphosphatemia. Increased release of endogenous phosphorus can be seen in association with any clinical condition that results in cell destruction, including rhabdomyolysis, tumor lysis syndrome, hemolysis, sepsis, severe hypothermia, and malignant hyperthermia. Excessive phosphate administration from IV hyperalimentation solutions or phosphorus-containing laxatives may also lead to elevated phosphate levels. Most cases of hyperphosphatemia are asymptomatic, but significant prolonged hyperphosphatemia can lead to metastatic deposition of soft tissue calcium-phosphorus complexes.
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Hypophosphatemia can be due to a decrease in phosphorus intake, an intracellular shift of phosphorus, or an increase in phosphorus excretion. Decreased GI uptake due to malabsorption or administration of phosphate binders and decreased dietary intake from malnutrition are causes of chronic hypophosphatemia. Most acute cases are due to an intracellular shift of phosphorus in association with respiratory alkalosis, insulin therapy, refeeding syndrome, and hungry bone syndrome. Clinical manifestations of hypophosphatemia usually are absent until levels fall significantly. In general, symptoms are related to adverse effects on the oxygen availability of tissue and to a decrease in high-energy phosphates, and can be manifested as cardiac dysfunction or muscle weakness.
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Magnesium Abnormalities
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Magnesium is the fourth most common mineral in the body and, like potassium, is found primarily in the intracellular compartments. Approximately one half of the total body content of 2000 mEq is incorporated in bone and is slowly exchangeable. Of the fraction found in the extracellular space, one third is bound to serum albumin. Therefore, the plasma level of magnesium may be a poor indicator of total body stores in the presence of hypoalbuminemia. Magnesium should be replaced until levels are in the upper limit of normal. The normal dietary intake is approximately 20 mEq/d and is excreted in both the feces and urine. The kidneys have a remarkable ability to conserve magnesium, with renal excretion <1 mEq/d during magnesium deficiency.
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Hypermagnesemia is rare but can be seen with severe renal insufficiency and parallel changes in potassium excretion. Magnesium-containing antacids and laxatives can produce toxic levels in patients with renal failure. Excess intake in conjunction with total parenteral nutrition (TPN), or rarely massive trauma, thermal injury, and severe acidosis, may be associated with symptomatic hypermagnesemia. Clinical examination (see Table 3-6) may find nausea and vomiting; neuromuscular dysfunction with weakness, lethargy, and hyporeflexia; and impaired cardiac conduction leading to hypotension and arrest. ECG changes are similar to those seen with hyperkalemia and include increased PR interval, widened QRS complex, and elevated T waves.
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Magnesium depletion is a common problem in hospitalized patients, particularly in the critically ill.16 The kidney is primarily responsible for magnesium homeostasis through regulation by calcium/magnesium receptors on the renal tubular cells that respond to serum magnesium concentrations.17 Hypomagnesemia may result from alterations of intake, renal excretion, and pathologic losses. Poor intake may occur in cases of starvation, alcoholism, prolonged IV fluid therapy, and TPN with inadequate supplementation of magnesium. Losses are seen in cases of increased renal excretion from alcohol abuse, diuretic use, administration of amphotericin B, and primary aldosteronism, as well as GI losses from diarrhea, malabsorption, and acute pancreatitis. The magnesium ion is essential for proper function of many enzyme systems. Depletion is characterized by neuromuscular and central nervous system hyperactivity. Symptoms are similar to those of calcium deficiency, including hyperactive reflexes, muscle tremors, tetany, and positive Chvostek’s and Trousseau’s signs (see Table 3-6). Severe deficiencies can lead to delirium and seizures. A number of ECG changes also can occur and include prolonged QT and PR intervals, ST-segment depression, flattening or inversion of P waves, torsades de pointes, and arrhythmias. Hypomagnesemia is important not only because of its direct effects on the nervous system but also because it can produce hypocalcemia and lead to persistent hypokalemia. When hypokalemia or hypocalcemia coexists with hypomagnesemia, magnesium should be aggressively replaced to assist in restoring potassium or calcium homeostasis.
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Acid-Base Homeostasis
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The pH of body fluids is maintained within a narrow range despite the ability of the kidneys to generate large amounts of HCO3− and the normal large acid load produced as a by-product of metabolism. This endogenous acid load is efficiently neutralized by buffer systems and ultimately excreted by the lungs and kidneys.
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Important buffers include intracellular proteins and phosphates and the extracellular bicarbonate–carbonic acid system. Compensation for acid-base derangements can be by respiratory mechanisms (for metabolic derangements) or metabolic mechanisms (for respiratory derangements). Changes in ventilation in response to metabolic abnormalities are mediated by hydrogen-sensitive chemoreceptors found in the carotid body and brain stem. Acidosis stimulates the chemoreceptors to increase ventilation, whereas alkalosis decreases the activity of the chemoreceptors and thus decreases ventilation. The kidneys provide compensation for respiratory abnormalities by either increasing or decreasing bicarbonate reabsorption in response to respiratory acidosis or alkalosis, respectively. Unlike the prompt change in ventilation that occurs with metabolic abnormalities, the compensatory response in the kidneys to respiratory abnormalities is delayed. Significant compensation may not begin for 6 hours and then may continue for several days. Because of this delayed compensatory response, respiratory acid-base derangements before renal compensation are classified as acute, whereas those persisting after renal compensation are categorized as chronic. The predicted compensatory changes in response to metabolic or respiratory derangements are listed in Table 3-7.18 If the predicted change in pH is exceeded, then a mixed acid-base abnormality may be present (Table 3-8).
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Metabolic Derangements
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Metabolic Acidosis Metabolic acidosis results from an increased intake of acids, an increased generation of acids, or an increased loss of bicarbonate (Table 3-9). The body responds by several mechanisms, including producing buffers (extracellular bicarbonate and intracellular buffers from bone and muscle), increasing ventilation (Kussmaul’s respirations), and increasing renal reabsorption and generation of bicarbonate. The kidney also will increase secretion of hydrogen and thus increase urinary excretion of NH4+ (H+ + NH3+ = NH4+). Evaluation of a patient with a low serum bicarbonate level and metabolic acidosis includes determination of the anion gap (AG), an index of unmeasured anions.
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The normal AG is <12 mmol/L and is due primarily to the albumin effect, so that the estimated AG must be adjusted for albumin (hypoalbuminemia reduces the AG).19
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Corrected AG = actual AG – [2.5(4.5 – albumin)]
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Metabolic acidosis with an increased AG occurs either from ingestion of exogenous acid such as from ethylene glycol, salicylates, or methanol, or from increased endogenous acid production of the following:
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β-Hydroxybutyrate and acetoacetate in ketoacidosis
Lactate in lactic acidosis
Organic acids in renal insufficiency
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A common cause of severe metabolic acidosis in surgical patients is lactic acidosis. In circulatory shock, lactate is produced in the presence of hypoxia from inadequate tissue perfusion. The treatment is to restore perfusion with volume resuscitation rather than to attempt to correct the abnormality with exogenous bicarbonate. With adequate perfusion, the lactic acid is rapidly metabolized by the liver and the pH level returns to normal. In clinical studies of lactic acidosis and ketoacidosis, the administration of bicarbonate has not reduced morbidity or mortality or improved cellular function.20 The overzealous administration of bicarbonate can lead to metabolic alkalosis, which shifts the oxyhemoglobin dissociation curve to the left; this interferes with oxygen unloading at the tissue level and can be associated with arrhythmias that are difficult to treat. An additional disadvantage is that sodium bicarbonate actually can exacerbate intracellular acidosis. Administered bicarbonate can combine with the excess hydrogen ions to form carbonic acid; this is then converted to CO2 and water, which thus raises the partial pressure of CO2 (Pco2). This hypercarbia could compound ventilation abnormalities in patients with underlying acute respiratory distress syndrome. This CO2 can diffuse into cells, but bicarbonate remains extracellular, which thus worsens intracellular acidosis. Clinically, lactate levels may not be useful in directing resuscitation, although lactate levels may be higher in nonsurvivors of serious injury.21
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Metabolic acidosis with a normal AG results from exogenous acid administration (HCl or NH4+), from loss of bicarbonate due to GI disorders such as diarrhea and fistulas or ureterosigmoidostomy, or from renal losses. In these settings, the bicarbonate loss is accompanied by a gain of chloride; thus, the AG remains unchanged. To determine whether the loss of bicarbonate has a renal cause, the urinary [NH4+] can be measured. A low urinary [NH4+] in the face of hyperchloremic acidosis would indicate that the kidney is the site of loss, and evaluation for renal tubular acidosis should be undertaken. Proximal renal tubular acidosis results from decreased tubular reabsorption of HCO3−, whereas distal renal tubular acidosis results from decreased acid excretion. The carbonic anhydrase inhibitor acetazolamide also causes bicarbonate loss from the kidneys.
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Normal acid-base homeostasis prevents metabolic alkalosis from developing unless both an increase in bicarbonate generation and impaired renal excretion of bicarbonate occur (Table 3-10). Metabolic alkalosis results from the loss of fixed acids or the gain of bicarbonate and is worsened by potassium depletion. The majority of patients also will have hypokalemia, because extracellular potassium ions exchange with intracellular hydrogen ions and allow the hydrogen ions to buffer excess HCO3–. Hypochloremic and hypokalemic metabolic alkalosis can occur from isolated loss of gastric contents in infants with pyloric stenosis or adults with duodenal ulcer disease. Unlike vomiting associated with an open pylorus, which involves a loss of gastric as well as pancreatic, biliary, and intestinal secretions, vomiting with an obstructed pylorus results only in the loss of gastric fluid, which is high in chloride and hydrogen, and therefore results in a hypochloremic alkalosis. Initially the urinary bicarbonate level is high in compensation for the alkalosis. Hydrogen ion reabsorption also ensues, with an accompanied potassium ion excretion. In response to the associated volume deficit, aldosterone-mediated sodium reabsorption increases potassium excretion. The resulting hypokalemia leads to the excretion of hydrogen ions in the face of alkalosis, a paradoxic aciduria. Treatment includes replacement of the volume deficit with isotonic saline and then potassium replacement once adequate urine output is achieved.
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Respiratory Derangements
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Under normal circumstances blood Pco2 is tightly maintained by alveolar ventilation, controlled by the respiratory centers in the pons and medulla oblongata.
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Respiratory acidosis is associated with the retention of CO2 secondary to decreased alveolar ventilation. The principal causes are listed in Table 3-11. Because compensation is primarily a renal mechanism, it is a delayed response. Treatment of acute respiratory acidosis is directed at the underlying cause. Measures to ensure adequate ventilation are also initiated. This may entail patient-initiated volume expansion using noninvasive bilevel positive airway pressure or may require endotracheal intubation to increase minute ventilation. In the chronic form of respiratory acidosis, the partial pressure of arterial CO2 remains elevated and the bicarbonate concentration rises slowly as renal compensation occurs.
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Respiratory Alkalosis
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In the surgical patient, most cases of respiratory alkalosis are acute and secondary to alveolar hyperventilation. Causes include pain, anxiety, and neurologic disorders, including central nervous system injury and assisted ventilation. Drugs such as salicylates, fever, gram-negative bacteremia, thyrotoxicosis, and hypoxemia are other possibilities. Acute hypocapnia can cause an uptake of potassium and phosphate into cells and increased binding of calcium to albumin, leading to symptomatic hypokalemia, hypophosphatemia, and hypocalcemia with subsequent arrhythmias, paresthesias, muscle cramps, and seizures. Treatment should be directed at the underlying cause, but direct treatment of the hyperventilation using controlled ventilation may also be required.