Electrolytes/Acid-Base Balance

SODIUM

In most cases, disturbances of sodium concentration [Na_] result from abnormalities of water homeostasis.Disorders of Na_ balance usually lead to hypoor hypervolemia.Attention to the dysregulation of volume (Na_ balance) and osmolality (water balance) must be considered separately for each pt (see below).

HYPONATREMIA

This is defined as a serum [Na_] _ 135 mmol/L and is among the most common electrolyte abnormalities encountered in hospitalized pts.Symptoms include confusion, lethargy, and disorientation; if severe (_120 mmol/L) and abrupt, seizures or coma may develop.Hyponatremia is often iatrogenic and almost always the result of an abnormality in the action of antidiuretic hormone (ADH), deemed either “appropriate” or “inappropriate,” depending on the associated clinical conditions.The serum [Na_] by itself does not yield diagnostic information regarding the total-body Na_ content.Therefore, a useful way to categorize pts with hyponatremia is to place them into three groups, depending on the volume status (i.e., hypovolemic, euvolemic, and hypervolemic hyponatremia). 

Hypovolemic Hyponatremia

Mild to moderate degrees of hyponatremia ([Na_] _ 125–135 mmol/L) complicate GI fluid or blood loss for two reasons. First, there is activation of the three major “systems” responsive to reduced organ perfusion: the renin-angiotensin-aldosterone axis, the sympathetic nervous system, and ADH.This sets the stage for enhanced renal absorption of solutes and water.Second, replacement fluid before hospitalization or other intervention is usually hypotonic (e.g., water, fruit juices). The optimal treatment of hypovolemic hyponatremia is volume administration, either in the form of colloid or isotonic crystalloid (e.g., 0.9% NaCl or lactated Ringer’s solution).

Hypervolemic Hyponatremia

The edematous disorders (CHF, hepatic cirrhosis, and nephrotic syndrome) are often associated with mild to moderate degrees of hyponatremia ([Na_] _ 125–135 mmol/L); occasionally, pts with severe CHF or cirrhosis may present with serum [Na_] _120 mmol/L.The pathophysiology is similar to that in hypovolemic hyponatremia, except that perfusion is decreased due to (1) reduced cardiac output, (2) arteriovenous shunting, and (3) severe hypoproteinemia, respectively, rather than true volume depletion.The scenario is sometimes referred to as reduced “effective circulating arterial volume.” The evolution of hyponatremia is the same: increased water reabsorption due to ADH, complicated by hypotonic fluid replacement. This problem may be compounded by increased thirst.Pts with a variety of causes of chronic kidney disease may also develop hypervolemic hyponatremia, due principally to salt and water retention due to reduced GFR, and to the diseased kidneys’ inability to osmoregulate.  Management consists of treatment of the underlying disorder (e.g., afterload reduction in heart failure, large-volume paracentesis in cirrhosis, glucocorticoid therapy in some forms of nephrotic syndrome), Na_ restriction, diuretic therapy, and, in some pts, H2O restriction.This approach is quite distinct from that applied to hypovolemic hyponatremia. 

Euvolemic Hyponatremia

The syndrome of inappropriate ADH secretion (SIADH) characterizes most cases of euvolemic hyponatremia.Common causes  of the syndrome are pulmonary (e.g., pneumonia, tuberculosis, pleural effusion) and CNS diseases (e.g., tumor, subarachnoid hemorrhage, meningitis); SIADH also occurs with malignancies (e.g., small cell carcinoma of the lung) and drugs (e.g., chlorpropamide, carbamazepine, narcotic analgesics, cyclophosphamide). Optimal treatment of euvolemic hyponatremia is H2O restriction to _1 L/d, depending on the severity of the syndrome. 

TREATMENT

The rate of correction should be relatively slow (0.5 mmol/L per h of Na_). A useful “rule of thumb” is to limit the change in mmol/L of Na_ to half of the total difference within the first 24 h.More rapid correction has been associated with central pontine myelinolysis, especially if the hyponatremia has been of long standing.More rapid correction (with the potential addition of hypertonic saline to the above-recommended regimens) should be reserved for pts with very severe degrees of hyponatremia and ongoing neurologic compromise (e.g., a pt with Na_ _105 mmol/L in status epilepticus). 

HYPERNATREMIA

This is rarely associated with hypervolemia, and this association is always iatrogenic, e.g., administration of hypertonic sodium bicarbonate.Rather, hypernatremia is almost always the result of a combined water and volume deficit, with losses of H2O in excess of Na_.The most common causes are osmotic diuresis secondary to hyperglycemia, azotemia, or drugs (radiocontrast, mannitol, etc.) or central or nephrogenic diabetes insipidus (DI) (see “Urinary Abnormalities,” Chap.56). Elderly individuals with reduced thirst and/or diminished access to fluids are at highest risk. 

TREATMENT

The approach to correction of hypernatremia is outlined in Table 3-1.As with hyponatremia, it is advisable to correct the water deficit slowly to avoid neurologic compromise.In addition to the water-replacement formula provided, other forms of therapy may be helpful in selected cases of hypernatremia.Pts with central DI may respond well to the administration of intranasal desmopressin.Pts  with nephrogenic DI due to lithium may reduce their polyuria with amiloride (2.5–10 mg/d) or hydrochlorothiazide (12.5–50 mg/d) or both in combination.Paradoxically, the use of diuretics may decrease distal nephron filtrate delivery, thereby reducing free-water losses and polyuria.Occasionally, NSAIDs have also been used to treat polyuria associated with nephrogenic DI; however, their nephrotoxic potential makes them a less attractive therapeutic option. 

POTASSIUM

Since potassium (K_) is the major intracellular cation, discussion of disorders of K_ balance must take into consideration changes in the exchange of intraand extracellular K_ stores (extracellular K_ constitutes _2% of total-body K_ content).Insulin, _2-adrenergic agonists, and alkalosis tend to promote K_ uptake by cells; acidosis promotes shifting of K_.

HYPOKALEMIA

Major causes of hypokalemia are outlined in Table 3- 2.Atrial and ventricular arrhythmias are the major health consequences of hypokalemia. Pts with concurrent magnesium deficit (e.g., after diuretic therapy) and/or digoxin therapy are at particularly increased risk.Other clinical manifestations include muscle weakness, which may be profound at serum [K_] _2.5 mmol/L, and, if prolonged, ileus and polyuria. Clinical history and urinary [K_] are most helpful in distinguishing causes of hypokalemia.

TREATMENT

Hypokalemia is most often managed by correction of the acute underlying disease process (e.g., diarrhea) or withdrawal of an offending medication (e.g., loop or thiazide diuretic), along with oral K_ supplementation with KCl, or, in rare cases, KHCO3 or K-acetate.Hypokalemia may be refractory to correction in the presence of magnesium deficiency; both cations may need to be supplemented in selected cases (e.g., cisplatin nephrotoxicity). If loop or thiazide diuretic therapy cannot be discontinued, a distal tubular K-sparing agent, such as amiloride or spironolactone, can be added to the regimen.ACE inhibition in pts with CHF attenuates diuretic-induced hypokalemia and protects against cardiac arrhythmia.If hypokalemia is severe (_2.5 mmol/L) and/ or if oral supplementation is not tolerated, intravenous KCl can be administered through a central vein at rates which must not exceed 20 mmol/h, with telemetry and skilled monitoring. 

HYPERKALEMIA

Causes are outlined in Table 3-3.In most cases, hyperkalemia is due to decreased K_ excretion.Drugs can be implicated in many cases.Where the diagnosis is uncertain, calculation of the transtubular K  gradient (TTKG) can be helpful.TTKG _ UKPOSM/PKUOSM (U, urine; P, plasma). TTKG _ 10 suggests decreased K_ excretion due to (1) hypoaldosteronism, or (2) renal resistance to the effects of mineralocorticoid.These can be differentiated by the administration of fludrocortisone (Florinef) 0.2 mg, with the former increasing K_ excretion (and decreasing TTKG). The most important consequence of hyperkalemia is altered cardiac conduction, leading to bradycardic cardiac arrest in severe cases.Hypocalcemia and acidosis accentuate the cardiac effects of hyperkalemia.Figure 3-1 shows serial ECG patterns of hyperkalemia.Stepwise treatment of hyperkalemia is summarized in Table 3-4. 

ACID-BASE DISORDERS (See Fig.3-2)

Regulation of normal pH (7.35–7.45) depends on both the lungs and kidneys. By the Henderson-Hasselbalch equation, pH is a function of the ratio of HCO3 _ (regulated by the kidney) to PCO (regulated by the lungs).The HCO3/PCO re- 2 2 lationship is useful in classifying disorders of acid-base balance.Acidosis is due to gain of acid or loss of alkali; causes may be metabolic (fall in serum HCO3 _) or respiratory (rise in PCO ).Alkalosis is due to loss of acid or addition 2 of base and is either metabolic (qserum HCO3) or respiratory (pPCO ). 2 To limit the change in pH, metabolic disorders evoke an immediate compensatory response in ventilation; compensation to respiratory disorders by the kidneys takes days.Simple acid-base disorders consist of one primary disturbance and its compensatory response.In mixed disorders, a combination of primary disturbances is present.Mixed disorders should be suspected when the change in anion gap is significantly higher or lower than the change in serum HCO3 _  

METABOLIC ACIDOSIS

The low HCO3 _ results from the addition of acids (organic or inorganic) or loss of HCO3 _.The causes of metabolic acidosis are categorized by the anion gap, which equals Na_ _ (Cl_ _ HCO3 _) (Table 3-5).Increased anion gap acidosis (_12 mmol/L) is due to addition of acid (other than HCl) and unmeasured anions to the body.Causes include ketoacidosis (diabetes mellitus, starvation, alcohol), lactic acidosis, poisoning (salicylates, ethylene glycol, and ethanol), and renal failure. Diagnosis may be made by measuring BUN, creatinine, glucose, lactate, serum ketones, and serum osmolality and obtaining a toxic screen.Certain commonly prescribed drugs (e.g., metformin, antiretroviral agents) are occasionally associated with lactic acidosis.  Normal anion gap acidoses result from HCO3 _ loss from the GI tract or from the kidney, e.g., renal tubular acidosis, urinary obstruction, rapid volume expansion with saline-containing solutions, and administration of NH4Cl, lysine HCl.Calculation of urinary anion gap may be helpful in evaluation of hyperchloremic metabolic acidosis.A negative anion gap suggests GI losses; a positive anion gap suggests altered urinary acidification. Clinical features of acidosis include hyperventilation, cardiovascular collapse, and nonspecific symptoms ranging from anorexia to coma.

TREATMENT

Depends on cause and severity.Always correct the underlying disturbance. Administration of alkali is controversial.It may be reasonable to treat lactic acidosis with intravenous HCO3 _ at a rate sufficient to maintain a plasma HCO3 _ of 8–10 mmol/L and pH _ 7.10. Lactic acidosis associated with cardiogenic shock may be worsened by bicarbonate administration. Chronic acidosis should be treated when HCO3 _ _ 18–20 mmol/L or symptoms of anorexia or fatigue are present.In pts with renal failure, there is some evidence that acidosis promotes protein catabolism and may worsen bone disease.Na citrate may be more palatable than oral NaHCO3, although the former should be avoided in pts with advanced renal insufficiency, as it augments aluminum absorption.Oral therapy with NaHCO3 usually begins with 650 mg tid and is titrated upward to maintain desired serum [HCO3_]. Other therapies for lactic acidosis remain unproven. 

METABOLIC ALKALOSIS

A primary increase in serum [HCO3]. Most cases originate with volume concentration and loss of acid from the stomach or kidney.Less commonly, HCO3 _ administered or derived from endogenous lactate is the cause and is perpetuated when renal HCO3 _ reabsorption continues.In vomiting, Cl_ loss reduces its availability for renal reabsorption with Na_.Enhanced Na_ avidity due to volume depletion then accelerates HCO3 _ reabsorption and sustains the alkalosis.Urine Cl_ is typically low (_10 mmol/L) (Table 3-6).Alkalosis may also be maintained by hyperaldosteronism, due to enhancement of H_ secretion and HCO3_ reabsorption.Severe K_ depletion also causes metabolic alkalosis by increasing HCO3 _ reabsorption; urine Cl_ _ 20 mmol/L. Vomiting and nasogastric drainage cause HCl and volume loss, kaliuresis, and alkalosis.Diuretics are a common cause of alkalosis due to volume contraction, Cl_ depletion, and hypokalemia.Pts with chronic pulmonary disease and high PCO and serum HCO3 _ levels whose ventilation is acutely improved 2 may develop alkalosis.  Excessive mineralocorticoid activity due to Cushing’s syndrome (worse in ectopic ACTH or primary hyperaldosteronism) causes metabolic alkalosis not associated with volume or Cl_ depletion and not responsive to NaCl. Severe K_ depletion also causes metabolic alkalosis. 

Diagnosis

The [Cl_] from a random urine sample is useful unless diuretics have been administered.Determining the fractional excretion of Cl_, rather than the fractional excretion of Na_, is the best way to identify an alkalosis responsive to volume expansion. 

TREATMENT

Correct the underlying cause.In cases of Cl_ depletion, administer NaCl; with hypokalemia, add KCl.Pts with adrenal hyperfunction require treatment of the underlying disorder.Severe alkalosis may require, in addition, treatment with acidifying agents such as NaCl, HCl, or acetazolamide.The initial amount of H_ needed (in mmol) should be calculated from 0.5 _ (body wt in kg) _ (serum HCO3 _ _ 24).

RESPIRATORY ACIDOSIS

Characterized by CO2 retention due to ventilatory failure.Causes include sedatives, stroke, chronic pulmonary disease, airway obstruction, severe pulmonary edema, neuromuscular disorders, and cardiopulmonary arrest.Symptoms include confusion, asterixis, and obtundation. 

TREATMENT

The goal is to improve ventilation through pulmonary toilet and reversal of bronchospasm.Intubation may be required in severe acute cases. Acidosis due to  hypercapnia is usually mild.Respiratory acidosis may accompany low tidal volume ventilation in ICU patients and may require metabolic “overcorrection” to maintain a neutral pH. 

RESPIRATORY ALKALOSIS

Excessive ventilation causes a primary reduction in CO2 andqpH in pneumonia, pulmonary edema, interstitial lung disease, asthma.Pain and psychogenic causes are common; other etiologies include fever, hypoxemia, sepsis, delirium tremens, salicylates, hepatic failure, mechanical overventilation, and CNS lesions.Pregnancy is associated with a mild respiratory alkalosis.Severe respiratory alkalosis may cause seizures, tetany, cardiac arrhythmias, or loss of consciousness. 

TREATMENT

Should be directed at the underlying disorders.In psychogenic cases, sedation or a rebreathing bag may be required.

“MIXED” DISORDERS

In many circumstances, more than a single acidbase disturbance exists.Examples include combined metabolic and respiratory acidosis with cardiogenic shock; metabolic alkalosis and acidosis in pts with vomiting and diabetic ketoacidosis; metabolic acidosis with respiratory alkalosis in pts with sepsis.The diagnosis may be clinically evident or suggested by relationships between the PCO and HCO3 _ that are markedly different from 2 those found in simple disorders. In simple anion-gap acidosis, anion gap increases in proportion to fall in [HCO3].When increase in anion gap occurs despite a normal [HCO3], simultaneous anion-gap acidosis and metabolic alkalosis are suggested.When fall in [HCO3] due to metabolic acidosis is proportionately larger than increase in anion gap, mixed anion-gap and non-anion-gap metabolic acidosis is suggested.