Acid-Base and Fluid and Electrolyte Disorders

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[edit] Acid-Base and Fluid and Electrolyte Disorders

Saulo Klahr

[edit] ACID-BASE DISORDERS

[edit] Acid-Base Balance in Health

The pH of blood is kept within a narrow range of 7.37 to 7.42.The range of plasma pH compatible with life is approximately 6.8 to 7.8.The pH of body fluids in humans is maintained despite the large production of acid from two major sources: (1) volatile carbonic acid (H₂CO₃), derived from carbon dioxide (CO₂), the end product of oxidative metabolism; and (2) a variety of nonvolatile acids produced from dietary substances, mainly protein.The pH of plasma is the ratio of bicarbonate (HCO₃⁻) to carbonic acid (dissolved CO₂), as formulated in the Henderson-Hasselbach equation:

where α, the solubility constant for CO₂, has a value of 0.03 at 37°C (98.6°F).In a normal individual, this expression has the following numeric values:

The denominator of the equation, the plasma carbon dioxide tension (Pco₂), is maintained within narrow limits by the excretion of CO₂by the lungs.Although pH changes are minimized through changes in extracellular fluid (ECF) Pco₂, the integrity of plasma pH depends on the availability of HCO₃⁻in the ECF.The kidneys participate in stabilizing the concentration of HCO₃⁻in plasma (the numerator of the Henderson-Hasselbalch equation).A normal individual ingesting 1 to 2 gm of protein per kilogram of body weight generates daily about 60 mmol of nonvolatile acid.The same amount of HCO₃⁻is consumed in the ECF to buffer this surplus acid.The restoration of serum HCO₃⁻consumed in buffering either metabolically produced or exogenous acid loads occurs both by virtually complete reabsorption of filtered HCO₃⁻(reclamation) and by the regeneration of HCO₃⁻formed in conjunction with the excretion of titratable acid and ammonium (de novo synthesis of HCO₃⁻).Both the reabsorption and the regeneration of HCO₃⁻result from the secretion of hydrogen ions (H⁺) into the nephron's tubular lumen.A rise in ECF HCO₃⁻levels is corrected by the renal excretion of a larger-than-normal fraction of the filtered HCO₃⁻.

[edit] Laboratory Considerations

Evaluation of a patient's acid-base status requires the measurement of two of the three values (pH, Pco₂, HCO₃⁻) in the Henderson-Hasselbalch equation.^[1] The third value can be calculated or read directly from a nomogram (Fig.145-1).The initial test for evaluating a patient's acid-base status should be the measurement of the total CO₂content of plasma or serum.This value reflects the total number of moles of CO₂liberated from both HCO₃⁻and H₂CO₃.Because of the relatively small amounts of H₂CO₃(1.3 mmol at a Pco₂of approximately 40 mm Hg), the value for the CO₂content approximates the HCO₃⁻concentration of plasma.Normal values for CO₂content are 26 to 28 mmol/L and can be measured in venous blood.Because the H₂CO₃/HCO₃⁻pair is the ECF's principal buffer system, measurement of the two components provides a meaningful and convenient expression of the organism's acid-base status.Two types of pathophysiologic events alter the pH: metabolic and respiratory.Metabolic acid-base disturbances result from processes that alter fluid pH primarily by changing the concentration of plasma HCO₃⁻(numerator of the Henderson-Hasselbach equation).Respiratory acid-base disorders result from primary changes in the respiratory component (denominator of the equation), which is measured as Pco₂.A series of overlapping defense mechanisms maintain the pH of the ECF within narrow limits.These mechanisms consist of at least three well-defined systems:

• Extracellular and intracellular buffers provide an almost instantaneous, first line of defense against changes in pH.
  
• Respiratory compensation of fairly rapid onset constitutes a secondary defense in metabolic disorders.
  
• The kidneys not only maintain plasma HCO₃⁻constant under normal circumstances but also modify HCO₃⁻excretion in respiratory acid-base disorders.The renal compensatory mechanism is slower to respond (several hours).
  

Figure 145-1 Acid-base nomogram.

[edit] Metabolic Acidosis

[edit] Clinical Features and Systemic Effects.

The clinical manifestations of metabolic acidosis in part may reflect the primary disorder responsible for the acidosis.The manifestations directly attributable to severe metabolic acidosis include depressed left ventricular function and decreased peripheral vascular resistance.^[1] This may lead to hypotension, pulmonary edema, arrhythmias (particularly ventricular fibrillation), and tissue hypoxia.The depth and rate of respirations increase; Kussmaul's respiration is especially prominent when plasma HCO₃⁻levels are below 15 mEq/L.Central nervous system manifestations include changes in mentation, confusion, and sometimes convulsions.Prolonged chronic metabolic acidosis may cause osteopenia and osteoporosis as a result of the buffering of H⁺by calcium carbonate (CaCO₃) in bone.This may contribute to bone disease, particularly in patients with chronic renal failure or renal tubular acidosis.

[edit] Laboratory Findings.

Metabolic acidosis occurs when the addition of H⁺to the extracellular space exceeds its rateof excretion, or when base is lost from the body in excess of its rate of replenishment.The hallmark of metabolic acidosis is a high H⁺concentration (low pH and low HCO₃⁻in plasma).Metabolic acidosis may also be suspected when a wide plasma anion gap (>15 mEq/L) exists, even in the absence of a pH or HCO₃⁻change.The anion gap is calculated by subtracting the sum of chloride (Cl⁻) plus HCO₃⁻concentrations from the sodium (Na⁺) concentration in plasma or serum:

Anion gap = Na⁺−(CI⁻+HCO₃⁻)

Normally a difference of 8 to 12 mEq/L exists, made up predominantly by plasma proteins, phosphate, and sulfate.

[edit] Causes.

Metabolic acidosis caused by a gain of H⁺is usually manifested by an increased anion gap (Table 145-1).Quantitatively the increased anion gap in plasma equals the decrease in plasma HCO₃⁻concentration.Metabolic acidosis resulting from loss of HCO₃⁻is characterized by a normal anion gap.In metabolic acidosis, the expected adjustment is a lowering of plasma Pco₂levels to minimize the decrease in pH.This is accomplished by an increase in the depth and rate of respiration.Quantitatively, the decrease in Pco₂from 40 mm Hg should equal the decrease in plasma HCO₃⁻from 26 mmol/L.Compensation at the level of the kidneys involves the excretion of increased amounts of ammonium to increase the de novo synthesis of HCO₃⁻.Normally the kidneys excrete 40 mmol of ammonium daily.During severe metabolic acidosis, ammonium excretion can reach 200 mmol daily.

Table 145-1 Causes of Metabolic Acidosis

[edit] Metabolic Acidosis Associated With Normal Anion Gap

[edit] Renal Loss of Bicarbonate

[edit] Use of carbonic anhydrase inhibitors.

Carbonic anhydrase inhibitors increase HCO₃⁻excretion in the urine by inhibiting the enzyme responsible for the hydration of CO₂.This process is key in the secretion of H⁺and consequently in HCO₃⁻reabsorption from the renal tubule.Such an inhibitor is acetazolamide (Diamox), a diuretic used to decrease intraocular pressure in patients with glaucoma.

[edit] Renal tubular acidosis.

Renal tubular acidosis (RTA) is a metabolic hyperchloremic acidosis that occurs in patients with a nonazotemic renal acidification defect.RTA is characterized by decreased H⁺excretion in the urine.The two major types of RTA are proximal and distal.^[1]

[edit] Distal RTA.

Distal, or classic, RTA is characterized by a defect of the distal nephron to excrete H⁺.The normal kidney can lower the urine pH to 4.7, a urine/plasma concentration ratio for H⁺of approximately 800:1.In contrast, in patients with distal RTA, the urine pH cannot fall below 6 regardless of the severity of the systemic acidosis.A urine pH of 6 limits the amount of H⁺excreted as ammonium or titratable acid (H⁺bound mainly to phosphate).The inability to excrete H⁺at a rate comparable to the rate of formation and consequently the failure to regenerate the HCO₃⁻consumed daily in the buffering process causes metabolic acidosis.Distal RTA is characterized by increased urine excretion of cations (sodium, potassium, calcium) and anions (sulfate, phosphate).This results in depletion of these cations with reduction of the ECF volume, hypokalemia, and rickets or osteomalacia.The increased calcium and phosphate excreted into the alkalineurine often cause renal stones or nephrocalcinosis.Distal RTA is seen in (1) a sporadic congenital primary form; (2) certain hypergammaglobulinemic states; (3) nephrocalcinosis, which may result from various genetic and metabolic disorders; (4) distal tubule nephrotoxicity caused by drugs such as amphotericin B, excessive vitamin D, and toluene; (5) medullary sponge kidney; and (6) interstitial renal disease (e.g., pyelonephritis, collagen disorders).Distal RTA may also develop after renal transplantation.

[edit] Proximal RTA.

Proximal RTA is characterized by a large excretion of HCO₃⁻in the urine.Alkaline urine is excreted, and hyperchloremic metabolic acidosis develops.Proximal RTA may be suspected by the presence of concomitant defects in proximal reabsorption, such as aminoaciduria, glycosuria, and phosphaturia.The hallmark of proximal RTA is normal acidification of the urine in the presence of normal renal function when plasma HCO₃⁻concentrations are low; excretion of an alkaline urine as plasma HCO₃⁻is raised by the administration of exogenous NaHCO₃⁻.

[edit] Gastrointestinal Loss of Bicarbonate.

HCO₃⁻loss through the gastrointestinal tract may lead to normal-anion-gap metabolic acidosis. Diarrhea may result in loss of fluid containing HCO₃⁻in excess (30 to 50 mmol/L) of the concentrations present in plasma.Large amounts of potassium may also be lost, and metabolic acidosis with hypokalemia may occur.Secretions from fistulas, the small bowel, the pancreas, or the biliary tract may be rich in HCO₃⁻.Losses of such fluids to the exterior may cause hyperchloremic acidosis.Patients with total cystectomies require the construction of artificial bladders in the form of an ileal loop conduit.Although hyperchloremic acidosis is uncommon in patients with ileal bladders, it may occur when the ileal segment is extremely long, when an antiperistaltic loop has been constructed, or when the stoma of the ileal loop is obstructed.Prolonged exposure of the urine to the ileal mucosa results in the exchange of chloride for HCO₃⁻, leading to loss of HCO₃⁻from body fluids.

Other causes of normal-anion-gap metabolic acidosis include expansion of the extracellular space with solutions not containing HCO₃⁻(dilutional acidosis) and the administration of hydrochloric acid, ammonium chloride, arginine, or lysine hydrochloride.Sometimes during hyperalimentation, amino acid infusions containing inorganic cations in excess of organic anions may cause a metabolic acidosis with hyperchloremia.^[1]

[edit] Metabolic Acidosis Associated With Increased Anion Gap.

An excess of acid is characterized by an increase in the anion gap.The acids that accumulate under these conditions are (1) keto acids, in insulin-deficiency diabetes; (2) lactic acid, in conditions characterized by tissue hypoxia; (3) acetylsalicylic acid (aspirin); and (4) toxic acids or substances that can be metabolized to them.Example of such substances are methanol, which leads to the formation of formic acid; ethylene glycol, which results in the formation of glyoxylic acid; paraldehyde, which is converted to acetic acid; and toluene, which is converted to hippuric acid.Patients with renal failure have increased-anion-gap metabolic acidosis (mainly caused by phosphate and sulfate), not because acid production is increased but because the kidney fails to regenerate enough HCO₃⁻.

When an increased anion gap occurs in metabolic acidosis, the diagnosis of ketoacidosis can be made if there are hyperglycemia, large concentrations of serum ketones, and a wide anion gap.Patients who fulfill these criteria usually have ECF volume contraction, hyperventilation, and thesmell of acetone on their breath.The treatment includes insulin to decrease the production of H⁺and sodium chloride to restore ECF volume.

Lactic acid, the end product of glycolysis, may accumulate in several conditions in which hypoxia is present (e.g., circulatory insufficiency, hypotension).Lactic acidosis can also occur during extreme exercise or the administration of phenformin or other uncouplers of oxidative phosphorylation.Loss of liver tissue may increase lactic acid levels as a result of decreased conversion of this acid to glucose.This also occurs when gluconeogenesis is impaired because of drugs or inborn errors of metabolism.

Finding an increased osmolar gap in the plasma of patients with metabolic acidosis should raise the suspicion of ethanol, methanol, isopropyl alcohol, or ethylene glycol intoxication.The osmolar gap is the difference between the measured serum osmolality and the calculated osmolality, as follows:

Calculated osmolality = 1.87 ([Na]+[K])+BUN/2.8 + glucose/18

[edit] Treatment.

The ideal treatment of metabolic acidosis corrects or ameliorates the cause.Only when acidosis accounts for severe physiologic disturbances is treatment of the acidosis itself required.Historically, the therapy has involved the administration of sodium bicarbonate (NaHCO₃).At present, such treatment is somewhat controversial, although the judicious use of NaHCO₃has been advocated.It is appropriate to administer HCO₃⁻if the blood pH is less than 7.1.

Chronic metabolic acidosis, which is caused by RTA or chronic renal failure, requires treatment in children to allow normal growth and in adults to ameliorate or prevent gastrointestinal or neurologic symptoms of acidosis and bone disease.NaHCO₃can be given to maintain plasma HCO₃⁻levels at about 20 mmol/L.Sodium overload should be avoided.In chronic metabolic acidosis, NaHCO₃may be given orally as tolerated.The 1-gm tablets contain 12 mmol of NaHCO₃.

[edit] Metabolic Alkalosis

The hallmark of metabolic alkalosis is an elevated blood pH resulting from an increase in the concentration of plasma HCO₃⁻.The increased plasma HCO₃⁻concentration may result from (1) the net loss of H⁺from the extracellular space or (2) the net addition of HCO₃⁻or its precursors to the extracellular space or loss of ECF-containing chloride in a concentration greater than HCO₃⁻.Therefore metabolic alkalosis results from abnormal loss of acid, excessive retention of base, or both.Normally, uncomplicated metabolic alkalosis is short-lived because the kidneys promptly excrete the excess HCO₃⁻.In established metabolic alkalosis, two mechanisms should be considered: the events responsible for the development of metabolic alkalosis (i.e., the generation of such an acid-base disorder) and the factors that allow this disorder to persist (i.e., the maintenance of metabolic alkalosis).The maintenance of metabolic alkalosis relates to an inability of the kidney to excrete HCO₃⁻.The factors that promote the renal tubular reabsorption of HCO₃⁻include contraction of the ECF volume, chloride deficit, decreased levels of plasma and intracellular potassium, and increased mineralocorticoid levels in plasma.^[1]

[edit] Clinical Features and Systemic Effects.

Metabolic alkalosis should be suspected in patients with a history of vomiting, surgery and gastric drainage, diuretic therapy, muscle cramps, and weakness and hypertension (primary hyperaldosteronism).Physical examination may reveal neuromuscular irritability such as tetany or hyperactive reflexes.These signs are more prominent if hypocalcemia is present, since the ionized calcium concentration decreases further as the pH rises.

[edit] Laboratory Findings.

Blood pH and plasma HCO₃⁻levels are increased, and arterial Pco₂rises as a compensatory mechanism.^[1] The Pco₂values, however, seldom exceed 50 mm Hg because the hypoventilation required to elevate the Pco₂further would also reduce arterial Po₂.The increased Pco₂and reduced Po₂in arterial blood stimulate the respiratory center, thereby tending to restore ventilation and blood gas levels toward normal.Occasionally, patients with metabolic alkalosis have marked hypercapnia (CO₂retention) that cannot be ascribed to accompanying pulmonary disease or neuromuscular weaknesses.The elevated Pco₂, sometimes in excess of 75 mm Hg, may be caused by alveolar hypoventilation from depression of the respiratory center.

Patients with metabolic alkalosis have an elevated total CO₂content, hypochloremia, and almost invariably, hypokalemia.Renal loss of potassium is the predominant cause of the last factor.Volume depletion may increase blood urea nitrogen (BUN) and creatinine concentrations in metabolic alkalosis.The hematocrit may be increased as a result of hemoconcentration.The anion gap may increase by as much as 5 to 6 mmol/L, partly because of higher concentrations of lactic acid and undefined anions.

The concentration of chloride in the urine is a useful test in the differential diagnosis of metabolic alkalosis.It may help distinguish metabolic alkalosis with volume expansion, which is mainly related to pathologic conditions of the adrenal gland, from metabolic alkalosis with volume depletion, which is mainly related to loss of fluid caused by vomiting or the use of diuretics.A urine chloride concentration below 10 mmol/L suggests avid reabsorption of NaCl by the renal tubule.A urine chloride concentration greater than 20 mmol/L in a patient with metabolic alkalosis indicates that neither ECF volume depletion nor chloride availability is a critical factor in perpetuating the metabolic alkalosis and points to excess mineralocorticoid activity as the cause of the disorder.In the analysis of chloride concentrations in patients who received diuretics 24 to 48 hours before a “spot” urinalysis, the validity of the previous assumptions is questionable.

[edit] Causes.

Box 145-1 presents the causes of metabolic alkalosis.Clinically, it is helpful to divide metabolic alkalosis into two categories: (1) with ECF volume contraction and (2) with ECF volume expansion, which is usually caused by excessive mineralocorticoid secretion.The latter form is often accompanied by hypertension.This hypertension may be accompanied by high plasma levels of renin and aldosterone, low renin and high aldosterone levels, or even low renin and low aldosterone levels.(In this case, other mineralocorticoids play a primary role in the expansion of the ECF and the increased excretion of potassium and hydrogen in the urine.) Patients with ECF volume contraction, except possibly for those with Bartter's syndrome, have low chlorideconcentrations in the urine.Excessive HCO₃⁻loads may cause metabolic alkalosis, but this occurs mainly in the setting of advanced renal insufficiency.

Several questions must be asked when evaluating a patient with metabolic alkalosis: Is the ECF volume contracted? Why is the ECF volume contracted? If ECF volume contraction exists, is the renal response appropriate? If ECF volume is normal or expanded, what should be done?

[edit] Treatment.

The underlying disease process causing the metabolic alkalosis should be treated.Treatment should also be directed at increasing renal HCO₃⁻excretion.Restoration of ECF volume in the form of NaCl plus potassium will increase the excretion of HCO₃⁻and retain NaCl and potassium in most varieties of metabolic alkalosis.Treatment of the excess mineralocorticoid varieties of metabolic alkalosis requires the removal or ablation of secretory tumors or the blockade of the renal tubular effects of the mineralocorticoids with spironolactone.Patients with severe potassium depletion and NaCl-resistant alkalosis may require large amounts of KCl before NaCl can be effective in correcting the alkalosis.

[edit] Respiratory Acidosis

Respiratory acidosis is characterized by an increase in Pco₂and a decrease in blood pH.It represents an imbalance between CO₂production and CO₂excretion by the lungs.^[2] The rise in Pco₂increases the concentration of H₂CO₃in body fluids.Since CO₂production from metabolism (13,000 to 15,000 mmol/day) tends to be constant, the increase in Pco₂is usually due to decreased excretion of CO₂via the lung.The first line of defense in respiratory acidosis is a chemical reaction in which the increased H₂CO₂resulting from increased Pco₂is buffered mainly by intracellular proteins and phosphate to mitigate a marked fall in pH.The second line of defense relates to increased H⁺excretion by the kidney and thus increased production of HCO₃⁻.In the initial phases of respiratory acidosis, the increased Pco₂stimulates the generation and secretion of H⁺.Increased excretion of titratable acid and particularly ammonium results in de novo generation of HCO₃⁻.

[edit] Clinical Features and Systemic Effects.

Respiratory acidosis can be acute or chronic.In acute respiratory acidosis, there is a marked and sudden decrease in the excretion of CO₂.The acute onset of hypercapnia (increased Pco₂) is usually accompanied by hypoxemia.The patient may have signs or symptoms of acute respiratory distress with marked restlessness, tachypnea, and dyspnea.As the process progresses, further manifestations include fatigue, weakness, confusion, hyperactivity and even manic periods, and headache.Coma occurs at levels of Pco₂from 70 to 100 mm Hg, depending on arterial pH and on the rapidity of elevation of Pco₂.Physical signs include tremor, asterixis (similar to hepatic encephalopathy), weakness, incoordination, occasional cranial nerve signs, abnormal pyramidal tract signs, papilledema, and retinal hemorrhages.

Patients with chronic respiratory acidosis have few, if any, signs or symptoms related directly to hypercapnia.The signs and symptoms of chronic pulmonary disease with or without cor pulmonale usually predominate.^[2]

[edit] Laboratory Findings.

There is a marked increase in Pco₂and sometimes a moderately elevated plasma HCO₃⁻.In acute respiratory acidosis, plasma HCO₃⁻concentrations rarely exceed 30 mmol/L.However, in chronic compensated respiratory acidosis, levels of HCO₃⁻may be as high as 40 mmol/L.In both chronic and acute varieties, the Po₂is generally decreased.The total plasma CO₂content is increased, usually with normal concentrations of sodium and potassium.Urine pH is usually acidic.In chronic respiratory acidosis, the plasma chloride value is greatly decreased.

[edit] Causes.

Box 145-2 summarizes the causes of respiratory acidosis.The differential diagnosis of acute vs.chronic respiratory acidosis relies on both the clinical and the laboratory criteria previously discussed.

[edit] Treatment.

The main goal in the treatment of acute respiratory acidosis is to restore effective ventilation.If a delay prevents achieving this goal, oxygen should be given at once.Modest amounts of NaHCO₃may be given intravenously to mitigate severe acidosis (blood pH <7.2).

Chronic respiratory acidosis can be treated effectively only by restoring or improving the lung's ability to excrete CO₂.This may be impossible because of irreversible lung changes.However, airway drainage (e.g., clearing secretions), relief of bronchospasm, and treatment of pulmonary infections and congestive heart failure may result in significant improvement.

[edit] Respiratory Alkalosis

Increased alveolar ventilation augments CO₂excretion, resulting in decreases in Pco₂, HCO₃⁻concentration, and H⁺concentration (reflected as a rise in blood pH).Since the production of CO₂from metabolism is usually constant, a negative CO₂balance can be achieved only through increasedalveolar ventilation.Hyperventilation may be caused by (1) increased neurochemical stimulation of the respiratory center and (2) iatrogenically assisted or controlled mechanical ventilation.Maintaining blood pH within normal limits as arterial Pco₂and thus H₂CO₃decrease requires that plasma HCO₃⁻decrease.The release of H⁺from body buffers reduces plasma HCO₃⁻levels.Changes in cellular metabolism also increase the production of lactic acid and probably other organic acids.In general, plasma HCO₃⁻levels decrease about 2.5 mmol/L for each decrement of 10 mm Hg in arterial Pco₂below normal.In respiratory alkalosis, HCO₃⁻values may occasionally decrease to as low as 15 mmol/L or arterial Pco₂to as low as 15 mm Hg, but metabolic acidosis should always be suspected when the plasma HCO₃⁻value is less than 18 mmol/L.The other line of defense in respiratory alkalosis is a diminished rate of H⁺secretion into the tubular fluid, leading to a HCO₃⁻diuresis that tends to restore pH toward normal.Ammonium excretion decreases, resulting in decreased de novo synthesis of HCO₃⁻.This renal adaptation to respiratory alkalosis occurs rapidly and is usually complete within 24 hours.^[2]

[edit] Clinical Features and Systemic Effects.

Respiratory alkalosis may cause neuromuscular irritability.Vasoconstriction of the cerebral circulation occurs, with reduced blood flow to the brain.Blood pressure and pulmonary vascular resistance are decreased, and pulmonary flow and cardiac output are increased.Patients may complain of paresthesias in the perioral region and extremities, muscle cramps, and tinnitus.In some patients, tetany and seizures occur, and an increase in deep tendon reflexes is present.Marked alkalosis may result in cardiac arrhythmias.^[2]

[edit] Laboratory Findings.

There is a decrease in the Pco₂of body fluids.Thus the arterial pH is elevated, and the plasma HCO₃⁻value decreases as a compensatory mechanism.The serum electrolyte levels remain within normal limits unless another disorder is present.The electrocardiogram (ECG) may show flattening or inversion of ST segments or T waves.The impaired release of oxygen from hemoglobin, caused by the shift in the oxyhemoglobin dissociation curve, may account for the ECG abnormalities in hypocapnia.A rise in blood concentrations of lactic acid and pyruvic acids in response to the reduction in Pco₂has been frequently observed.The clinician should consider the development of an HCO₃⁻deficit in the presence of a simultaneous rise in the concentrations of lactic and pyruvic acids in patients with respiratory alkalosis, since this HCO₃⁻deficit may be confused with the findings seen in metabolic acidosis with an increased anion gap.

[edit] Causes.

Box 145-3 lists the causes of respiratory alkalosis.It is important to note that the acid-base disorder produced by pulmonary disease depends on the severity of that disease.

[edit] Treatment.

Effective therapy corrects or ameliorates the basic disorder responsible for the hyperventilation.The correction of hypoxemia is critical.If the respiratory alkalosis is related to mechanical ventilation, decreasing the minute ventilation or increasing the dead space may be effective.If this cannot be done without compromising oxygenation, the use of an inhaled mixture containing 3% CO₂may be helpful.

[edit] Mixed Acid-Base Disorders

The entities described—metabolic acidosis or alkalosis and respiratory acidosis or alkalosis—represent simple acid-base disturbances.They denote the presence of one primary process and its appropriate physiologic response.A mixed acid-base disturbance refers to the coexistence of two or more primary processes.^[3] Since these processes may have either additive or nullifying effects on plasma pH, mixed acid-base disturbances may produce dramatically extreme deviations of H⁺concentration or disarmingly minor or undetectable deviations.

The coexistence of two or more simple acid-base disturbances is quite common in hospitalized patients.^[4][3] A mixed acid-base disturbance is frequently suspected from a careful analysis of the acid-base values.When the magnitude of the secondary change in Pco₂or HCO₃⁻concentrations (in metabolic and respiratory disorders, respectively) is inappropriate with respect to the magnitude of the initiating process, the presence of a mixed disturbance should be considered (Table 145-2).Even when a seemingly appropriate relationship exists between an initiating disturbance and an anticipated secondary response, such a relationship may merely be the consequence of a dual or even a triple acid-base abnormality.To avoid this diagnostic pitfall, the clinician should seek clues to the presence of complicating acid-base disturbances from a close examination of other laboratory data and particularly from the patient's history.^[4][3]

Table 145-2 Usual Magnitude of Compensatory Mechanism in Acid-Base Disorders

Chronic respiratory acidosis may coexist with metabolic alkalosis, particularly in patients with pulmonary insufficiencyand cor pulmonale treated with diuretics and a low-salt diet.This disturbance can also emerge when longstanding hypercapnia is partially corrected by mechanical ventilation or another means.^[4][3]

A combination of chronic and acute respiratory acidosis may be seen in patients with moderately severe CO₂retention caused by chronic obstructive lung disease who also experience a sudden worsening of pulmonary function from the use of sedatives capable of depressing the respiratory center, correction of their hypoxia by oxygen therapy, or concomitant acute pulmonary infections.

Metabolic acidosis plus acute respiratory acidosis is common in patients with acute cardiopulmonary arrest and results from lactic acidosis (triggered by poor tissue perfusion) and CO₂retention.A similar presentation may be seen in patients with severe, acute pulmonary edema.Extreme decreases in plasma pH may be seen under these conditions.

[edit] FLUID AND ELECTROLYTE DISORDERS

[edit] Disorders of Potassium: Homeostasis

Potassium is a cation located predominantly in the intracellular space.Total body potassium values approximate 3600 mmol, with the extracellular space containing only 65 to 70 mmol.Approximately 100 mmol of potassium is ingested daily in the average American diet.Under normal circumstances, 90% of this amount is excreted in the urine (80 to 90 mmol daily) and 10% in the stools (8 to 15 mmol daily).Because potassium is located primarily in the intracellular space (98%), it is difficult to accurately monitor changes in body stores of this cation.The distribution of potassium between the intracellular and extracellular fluids affects the potassium concentration in the plasma.Potassium homeostasis is regulated mainly by the kidney.Potassium excretion by the kidney is influenced by acid-base status, anion excretion, urine flow rate, potassium intake, and levels of mineralocorticoids.^[5]

[edit] Hypokalemia

Hypokalemia is usually defined as a plasma potassium concentration below 3.5 mEq/L.Hypokalemia may be relative or absolute.^[5] Acid-base changes may shift potassium into cells, causing relative hypokalemia (lower plasma concentration) when in fact total body potassium concentrations may be normal.Absolute hypokalemia is a decrease of both intracellular and extracellular potassium concentrations.For a decline of 1 mmol/L in plasma potassium levels, the total potassium deficit may be 100 to 400 mmol.

[edit] Clinical Features and Systemic Effects.

The organs usually affected by hypokalemia include skeletal muscle, heart, kidneys, and gastrointestinal tract.Clinical manifestations of mild hypokalemia may be subtle.A high degree of suspicion (history of vomiting, use of diuretics or laxatives, diarrhea) helps identify patients at risk.Most patients with plasma potassium levels below 2.5 mmol/L complain of moderate muscle weakness.When the potassium concentration falls below 1.5 mmol/L, areflexic paralysis may occur, and respiratory depression may be a threat to survival.Potassium also affects cardiac function.Acute potassium losses may cause hyperpolarization, since intracellular potassium levels may remain normal as extracellular potassium levels fall.This situation may cause premature ventricularcontractions, frequent ectopic tachycardias, and widening of the QRS complex.With small changes in the intracellular potassium concentration, which is related to myocardial contractility, cardiac output begins to fall.Significant changes in the ECG, including early depression of the ST segment with a decreased amplitude of the T wave, may be present.U waves, as well as first-degree atrioventricular block, may also be present.As intracellular potassium values decrease further, contractility progressively declines, leading to marked ventricular irregularity and profound heart failure.Potassium depletion also decreases gastric and small intestinal motility and may cause paralytic ileus.Severe prolonged potassium depletion causes histologic changes in the kidney and an inability to concentrate the urine, resulting in polyuria, polydipsia, and nocturia.

[edit] Causes.

Box 145-4 lists the causes of hypokalemia.In hypokalemic patients, it is important to assess blood pressure and the ECF volume status.Also, when hypokalemia is severe (plasma potassium level below 3 mmol/L), the clinician should consider causes other than, or in addition to, diuretic therapy.The determination of potassium excretion in the urine is important.Usually, individuals with hypokalemia caused by losses of potassium via the gastrointestinal tract have a urine potassium concentration less than 15 mmol/day.Magnesium depletion also may cause hypokalemia.Fig.145-2 outlines the evaluation of hypokalemia.

Figure 145-2 Evaluation of hypokalemia.

[edit] Treatment.

In most patients, correction of the potassium deficit is advised.Since potassium is located mainly intracellularly, it is difficult to judge the total deficit of potassium.The rapidity of potassium replacement depends on the chronicity of the disorder, the presence of other fluid and electrolyte abnormalities, and the presence and severity of end-organ sequelae of the hypokalemia.Specific salt use to replace a potassium deficit is important.With alkalosis, potassium must be replaced as potassium chloride.When hypokalemia is associated with metabolic acidosis, as in RTA or diabetic ketoacidosis, potassium replacement by potassium bicarbonate (KHCO₃) or a KHCO₃equivalent (potassium citrate or gluconate) can be effective.When derangements of hypokalemia are not life threatening, oral replacement of potassium is usually indicated.When intravenous potassium replacement is required, a rate of 10 mmol/hr without monitoring is safe.However, doses of 40 mmol/hr or higher should be given only with close ECG monitoring.Hypokalemia related to diuretic use, when diuretic therapy is necessary, may require the administration of potassium-sparing drugs such as triamterene or amiloride.These are usually more effective in correcting hypokalemia than potassium supplementation alone and also prevent concurrent magnesium loss by diuretics.

[edit] Hyperkalemia

Hyperkalemia is defined as a plasma potassium level higher than 5 mmol/L.It is a relatively uncommon clinical entity but has potentially lethal consequences.^[6][7] Hyperkalemia can be classified as relative or absolute.Relative hyperkalemia occurs with shifts of intracellular potassium to the extracellular fluid space without an increase in total body potassium values.Absolute hyperkalemia is present when both intracellular and extracellular potassium concentrations are increased.

[edit] Clinical Manifestations and Systemic Effects.

Patients with hyperkalemia develop cardiovascular and neuromuscular abnormalities.Cardiac contractility is not affected by hyperkalemia, but significant arrhythmias may occur because of changes in conduction.ECG changes usually occur when plasma potassium levels exceed 7 mmol/L.With modest increases in plasma potassium, tall, peaked T waves are seen with a normal QT interval, and decreased amplitude of the P waves occurs with a prolonged PR interval.As hyperkalemia progresses, atrial asystole is seen, with widening of the QRS complex leading to a sine wave.Finally, plasma potassium concentrations higher than 10 mmol/L lead to ventricular standstill.The effects of hyperkalemia on cardiac function can occur with smaller increases in plasma potassium values when hyponatremia, hypocalcemia, or acidosis is present.Changes in muscle strength or nerve conduction velocity also occur, particularly when potassium levels exceed 8 mmol/L.Muscular weakness develops, usually beginning in the lower extremities and ascending to the upper extremities.Respiratory depression may occur.

[edit] Causes.

Box 145-5 lists the most common causes of hyperkalemia.Acute and chronic renal failure account for most cases.Since the kidney is the major organ responsible for potassium excretion, a marked loss of renal function may cause hyperkalemia if dietary intake of potassium is not curtailed.^[6][7] Increased catabolism also plays a role in the development of hyperkalemia in patients with acute renal failure.Hyperkalemia is usually not seen in patients with chronic renal failure unless excessive potassium is administered.Hyperkalemia may occur as a result of translocation of potassium from the intracellular to the extracellular space.This may be caused by acidosis, severe tissue catabolism, muscle breakdown (rhabdomyolysis), and familial hyperkalemic periodic paralysis.Since aldosterone is a major regulatory hormone of potassium homeostasis, its absence may lead to hyperkalemia.Although isolated aldosterone deficiency is exceedingly rare, primary adrenal insufficiency (Addison's disease) may be associated with severe depression of plasma aldosterone levels.

Addison's disease resulting from hypopituitarism is not associated with hyperkalemia, since aldosterone secretion rates remain normal.Addison's disease resulting from pathologic conditions of the adrenal gland may lead to hyperkalemia.In addition, patients with this condition may have hyperpigmentation, decreased appetite, hypoglycemia, and hypotension (see Chapter 98 ).Hyponatremia and renal sodium wasting may also be observed.In hyporeninemic hypoaldosteronism, hyperkalemia may occur because of deficient aldosterone secretion and decreased secretion of potassium in the distal tubule.Approximately 50% of patients with hyporeninemic hypoaldosteronism have associated diabetes.About 50% of these patients achieve lower potassium levels with improved diabetic control.Spironolactones, aldosterone antagonists, or potassium-sparing diuretics may also cause hyperkalemia.

[edit] Treatment.

The treatment of hyperkalemia differs based on the level of plasma potassium, the chronicity of the hyperkalemic state, and clinical manifestations.In acute hyperkalemia, if the potassium concentration is less than 6.5 mmol/L and there are no ECG changes, potassium intake should be decreased and drugs that compromise potassium excretion discontinued.With greater levels of potassium or pertinent ECG changes, other measures are necessary.Calcium administration may reverse several effects of hyperkalemia.The effects of calcium therapy are seen within minutes, but they are short-lived, about half an hour.The redistribution of potassium from the extracellular to the intracellular space is also an effective treatment for hyperkalemia.This can be accomplished by the administration of NaHCO₃, one or two ampules (44 to 88 mmol) given intravenously, or by the infusion of glucose and insulin.A solution of 500 ml of 10% glucose with 10 units of regular insulin is an adequate dose for the latter treatment.The effects of glucose and insulin therapy are seen within 30 minutes and last for several hours.A β-agonist such as albuterol used as a nebulizer at doses of 10 to 20 mg lowers the serum potassium concentration by approximately 0.6 mmol/L.The effect of albuterol occurs within 30 minutes and persists for at least 2 hours.Restoration of extracellular volume may correct hyperkalemia.Potassium can be removed from the body using exchange resins such as sodium polystyrene sulfonate (Kayexalate), which can be administered orally or rectally.Hemodialysis or peritoneal dialysis can also be used to remove potassium.The effect of dialysis on plasma potassium is seen within hours, and its duration depends on the rate of the endogenous release of potassium.

[edit] Hyponatremia

Hyponatremia is defined as a serum sodium concentration below 135 mmol/L.It does not necessarily indicate a decrease in total body sodium levels.^[8] Since the concentration of sodium depends on the relative amounts of sodium and water in the ECF, a low serum sodium concentration indicates only that there is relatively more water than sodium in this space.This may occur when ECF sodium content is decreased, such as with diarrhea, in which losses of both sodium and water occur but the sodium losses are greater than those of water.When the ECF sodium content is normal (e.g., with excess administration of water) or when the ECF sodium content is increased (e.g., with edema), increases in both sodium and water content occur.Fig.145-3 summarizes an approach to the patient with hyponatremia.

Figure 145-3 Evaluation of hyponatremia. SIADH, Syndrome of inappropriate antidiuretic hormone (ADH) release.

Hyponatremia may occur in the setting of an expanded, normal, or contracted ECF volume.^[8] Excess water in the ECF may result from excessive intake or reduced excretion of water.Increased ingestion of water may occur as a result of compulsive polydipsia, acute psychosis, excessive parenteral administration of fluids, use of tap water enemas, or postoperative irrigation of the prostatic bed with hyponatremic solutions.Reduced excretion of water may result from intrinsic renal disease or extrinsic factors that modify the kidneys' ability to excrete water, such as the syndrome of inappropriate antidiuretic hormone (SIADH) (see Chapter 99 ), congestive heart failure, and cirrhosis.The first step in the evaluation of hyponatremia is to rule out hyperglycemia, hyperproteinemia, and hyperlipidemia as potential reasons for the pseudohyponatremia.With true hyponatremia, the osmolality of plasma is low.If sodium loss is the cause of the hyponatremia, urine sodium and chloride concentrations are less than 20 mmol/L.If the major reason for the hyponatremia is water excess, the excretion of a volume of 1 L hourly of dilute urine, 50 to 75 mOsm/kg water, is to be expected.

[edit] Clinical Manifestations and Systemic Effects.

Patients with hyponatremia rarely have symptoms unless the plasma sodium level is below 125 mmol/L and unless hyponatremia has developed rapidly.The typical symptoms relate to osmotic swelling of brain cells and vary from mild lethargy to convulsions and coma.There may also be gastrointestinal symptoms such as anorexia and nausea.

[edit] Treatment.

Treatment depends on whether the condition is acute or chronic.In acute hyponatremia, neurologic symptoms are more often seen in young female patients in the postoperative state, in elderly people receiving thiazide diuretics, and in patients with psychogenic polydipsia.These patients should be treated promptly to prevent cerebral edema and seizures.Rapid correction through the intravenous administration of sodium, 1.5 to 2.0 mM/L/hr in this setting, may be associated with a lower mortality rate than slower correction (0.6 mM/L/hour).However, central pontine myelinolysis may occur with too-rapid correction of marked hyponatremia.^[9] The correction can be accomplished with hypertonic saline, preferably given with furosemide to prevent sodium overload and to enhance water excretion.Symptomatic chronic hyponatremia is bestmanaged conservatively with water restriction even when the serum sodium concentration is very low.Prolonged water restriction may be difficult to enforce, and therefore agents that antagonize the renal action of ADH have been used.Demeclocycline is safer and more effective than lithium in the treatment of SIADH.

[edit] Hypernatremia

Hypernatremia is marked by plasma sodium concentrations in excess of 145 mmol/L.Disturbances of either sodium or water metabolism cause hypernatremia.^[10] This usually results from sodium gain or water loss.Physiologically, hypernatremia results in a decrease in cell volume.Hypernatremia is not a specific clinical entity.The clinician should look for the underlying cause of the increase in serum sodium concentration.Most often, hypernatremia is caused by water loss from renal or extrarenal sources.Daily obligatory fluid loss is related to evaporative losses through the lungs and skin plus the amount of water necessary to excrete the solutes in the urine.These obligatory fluid losses amount to about 1300 ml/day, or approximately 10% of the ECF volume.Obligatory sodium losses are much smaller.Daily losses of sodium in sweat and feces normally are less than 20 mmol.Urine sodium concentration can be reduced to below 5 mmol daily so that sodium loss can be reduced if necessary to an amount equal to less than 1% of the sodium pool in the ECF.If the daily losses of sodium and water are not replaced, the negative water balance exceeds that for sodium, and the sodium concentration in the extracellular space increases progressively.If the patient has fever or is in a high environmental temperature, the situation is aggravated because all these conditions increase evaporative water losses more than sodium loss.Water is not replaced in patients with nausea, vomiting, or dysphagia, who experience thirst consequent to the hypernatremia and are unable to increase their fluid intake appropriately.Comatose patients or those with cerebrovascular accidents (strokes) may not be aware of thirst or may not be able to communicate their needs.They depend on others for adequate fluid intake.Infants are particularly susceptible to hypernatremia.Their surface area per unit of body mass is much greater than that of the adult, so their evaporative water losses are greater.In addition, infants' ability to concentrate their urine is incompletely developed, increasing obligatory water losses.

When the major problem is loss of water in excess of sodium loss, volume contraction usually occurs, and laboratory studies show evidence of hemoconcentration with increasing hematocrit and serum protein concentrations.BUN and serum creatinine concentrations may be elevated.Unless the patient has coexistent renal disease, the urine output is low, less than 500 ml/day, and the urine is hyperosmolar, in excess of 1000 mOsm/kg water, with a very low urine sodium concentration.Failure to find a very low urine volume and a maximally concentrated urine suggests a renal problem.

The major renal causes of hypernatremia are diabetes insipidus (see Chapter 99 ) and an osmotic diuresis.These two disorders can be distinguished by measuring urine osmolality.When thirst is absent in patients with hypernatremia, a central nervous system lesion should be considered.Hypernatremia caused by sodium excess is rare.Usually, it is characterized by ECF volume expansion, thirst, and the excretion of small volumes of very concentrated urine.If the hypernatremia results from water loss of extrarenal origin and the patient does not have access to water, he or she will be thirsty and excrete a minimal volume of maximally concentrated urine.If the cause of the hypernatremia is loss of water via the kidney, the urine will not be concentrated and the urine volume will not be decreased.In this setting, two major diseases may be present: diabetes insipidus (central or nephrogenic) or diuretic-induced water loss (usually osmotic diuresis from glucose or urea).Fig.145-4 summarizes an approach to the patient with hypernatremia.

Figure 145-4 Evaluation of hypernatremia.

[edit] Clinical Manifestations and Systemic Effects.

As with hyponatremia, the principal clinical manifestations relate to osmotic effects on the brain.In hypernatremia, there is dehydration of brain cells, which leads to symptoms ranging from confusion to convulsions and coma.The intensity of the symptoms correlates with both the severity and the rapidity of development of the hypernatremia.

[edit] Treatment.

The primary goal is the restoration of serum tonicity.The following principles are helpful.If the patient is hypervolemic and hypernatremic, excess sodium should be removed, which can be achieved by the intravenous administration of diuretics along with 5% dextrose.If renal function is impaired, dialysis may be needed.If the patient has a low total body sodium concentration, isotonic NaCl should be given until systemic hemodynamics are stabilized.Hypernatremia is then treated with half-normal saline or 5% dextrose.The patient who is hypernatremic but euvolemic and therefore has sustained water losses almost exclusively requires replacement of water with a 5% dextrose infusion.

[edit] REFERENCES