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A metabolic alkalosis is a process that results in excessive accumulation of HCO3 in the plasma. (118) Arterial pH rises and results in alkalemia. A metabolic alkalosis can be produced by excessive HCO3 administration, but a healthy, well-perfused set of kidneys should excrete excess HCO3 , so this occurrence is limited to volume-depleted, K-depleted individuals or individuals with advanced renal insufficiency. (65) (70) More commonly, a metabolic alkalosis results from HCl loss from the body in association with volume and K loss, as with vomiting or the use of loop or thiazide diuretics (chloruretic diuretics). A primary hyperaldosteronemic state also results in alkalosis from K depletion and associated renal HCO3 retention. Discerning the etiology and pathogenesis of a metabolic alkalosis is important, for therapy must be directed toward the pathogenic and sustaining forces.
As with a metabolic acidosis, buffer response to a metabolic alkalosis is immediate and beneficial. Proteins and hemoglobin release free H when exposed to alkali excess, and bone appears to increase its deposition of carbonate. (118)
Since the primary disturbance in metabolic alkalosis is accumulation of HCO3 in the ECF, the expected ventilatory response to rising extracellular pH is depression of ventilation, which results in a rise in PCO2 . This
The expected renal response to a metabolic alkalosis is an eventual augmentation in renal HCO3 excretion. However, a characteristic feature of metabolic alkalosis is the fact that the kidney is unable to excrete the excess HCO3 . (65) (70) This adverse situation in fact accounts for the perpetuation of the metabolic alkalosis. As discussed later, responsible forces include concomitant chloride and intravascular volume depletion, hypokalemia, and rising PCO2 , all of which augment renal HCO3 reabsorption and stimulate renal HCO3 generation. (65) (70) Rather than compensate for the metabolic alkalosis, the kidney contributes to the alkalosis by adding HCO3 to the systemic circulation and hyperabsorbing filtered HCO3 . Typically, the urine pH is inappropriately acidic, indicating net acid excretion by the kidney--a process that malserves acid-base homeostasis in this context. Whether metabolic alkalosis arises from gastric HCl loss or renal HCl loss, renal processes that add HCO3 to the circulation and/or retard its excretion contribute centrally to the perpetration and perpetuation of the alkalosis.
Causes of metabolic alkalosis are numerous, but the essential pathophysiology is virtually the same in all circumstances: extracellular H+ loss and HCO3 gain, with renal retention and/or augmented generation of HCO3 . Two etiologic groupings of metabolic alkaloses are recognized: (1) hypovolemic, chloride-depleted alkaloses and (2) hypervolemic, chloride-expended metabolic alkaloses (Table 34-17) . An important feature common to both is K depletion.
Pathogenesis here involves loss of H, Cl, Na, K, and H2 O from the ECF. Routes of loss are either gastric or renal. Loss of H produces a relative surplus of HCO3 . Loss of Cl, Na, and H2 O produces contraction of the intravascular fluid volume and stimulation of renin-angiotensin-aldosterone output. These events in turn augment renal HCO3 reabsorption from the glomerular filtrate and HCO3 generation in the distal tubular epithelia. (65) (70) (87)
It is a well-known physiologic fact that the kidney ordinarily
excretes excess HCO3
that is presented to it via glomerular
filtration.
(34)
(65)
(70)
Augmentation of proximal HCO3
reabsorption results as the kidney responds to volume depletion
and augments proximal Na reabsorption. HCO3
is absorbed
indirectly via Na/H exchange in the proximal nephron.
(34)
Stimulation of proximal Na/H exchange occurs by
angiotensin, which is usually present in excess owing to hypovolemic
stimulation of renin output. Hypokalemia also
Distal nephron generation of HCO3 is stimulated by aldosterone and hypokalemia. Hyperaldosteronemia results from volume contraction and renin-angiotensin production. In this context, hyperaldosteronemia is secondary, not primary. Aldosterone has four actions in the distal tubular epithelia: opening of Na channels, opening of K channels, stimulation of H-ATPase on the luminal membranes, and stimulation of Na-K-ATPase on the basolateral membranes. (34) (144) Aldosterone thereby supports Na reabsorption and K secretion in this region of the nephron and aids H secretion. Stimulation of H secretion into tubular lumens is coupled to intracellular HCO3 generation and its respective entry into the peritubular capillaries. Hypokalemia also stimulates H secretion by inducing an intracellular acidosis.
It is important to emphasize that volume depletion alone does not generate a metabolic alkalosis. (87) Chloride, K, and H depletion must also evolve. Yet volume depletion is a central force in perpetuating a chloride-depletion alkalosis because volume depletion stimulates Na/H exchange in the proximal nephron and induces aldosterone output. (65) (70) The factors that generate a metabolic alkalosis are those that are primarily responsible for adding HCO3 to the ECF. HCl loss is the principal event. (118) The factors that perpetuate or maintain a metabolic alkalosis are those that prevent renal excretion of the surplus plasma HCO3 . Chloride depletion, volume depletion, hypokalemia, reduced distal nephron Cl delivery, and hyperaldosteronism are those forces. (34) (65) (70) (122)
The evolution of metabolic alkalosis in this class of disorders
Etiologic examples of this category of metabolic alkalosis are primary hyperaldosteronism and primary hypercortisolism. It is interesting that K repletion in these disorders can itself correct the alkalosis (118) (Table 34-17) .
In contrast to the chloride-depletion alkaloses, generation of the alkalosis in the chloride-expanded contexts depends on hypokalemia and hyperaldosteronemia. The kidney is the primary perpetrator of HCl loss. (34) (53) (65) (70) (118) Perpetuation of the alkalosis is also kidney dependent, but chloride independent. In chloride-depletion alkaloses, generation of the alkalosis occurs from a primary force that results in volume and HCl loss. Hypokalemia and hyperaldosteronemia are secondary occurrences that act to maintain the alkalosis. These facts have therapeutic implications.
Metabolic alkalosis is recognized from plasma (HCO3 ), arterial pH, and arterial PCO2 . Plasma (HCO3 ) will be rising along with arterial pH. Arterial PCO2 is also elevated. (101)
The cause of the metabolic alkalosis is usually discernible from the history and clinical context, where events such as vomiting, nasogastric suction, or diuretic use are obvious. Physical examination is also important because it may reveal evidence for volume contraction and orthostatic hypotension or conversely, hypertension in a patient with primary aldosteronism.
When the cause is not so obvious from the clinical history and examination, the urine (Cl) becomes important. Low urine (Cl) (less than 25 mEq/L) reflects volume depletion from vomiting, nasogastric suctioning, or diuretic use (unless diuretic action is still occurring), whereas a relatively high urine (Cl) (greater than 40 mEq/L) primary reflects mineralocorticoid excess with volume expansion or primary alkali overloading. (101) (118) A metabolic alkalosis is one clinical context in which the urine (Cl) becomes a more accurate reflection of effective intravascular volume than urine (Na) because Na must be excreted with excess HCO3 . Current diuretic use may give misleading information by causing urine (Cl) to be high in a fluid- and chloride-deplete patient. Likewise, severe hypokalemia can also cause a comparatively high urine (Cl) by causing a tubular defect in NaCl handling, even though the patient is relatively Cl deficient and most often intravascular volume contracted. Patients with chronic renal insufficiency may also exhibit relative Cl wasting in the face of fluid depletion because of the nephron adaptations that occur in chronic renal failure.
Treatment of metabolic alkalosis has two major objectives: (1) interruption of the primary etiologic forces responsible for generating the alkalosis and (2) interruption of the forces responsible for perpetuating the alkalosis. (65) (70) (100) (118) When a volume-depletion, chloride-depletion alkalosis is in process, therapy should primarily be directed at the forces responsible for HCl and fluid loss. Specific interventions may include antiemetics, mitigation of nasogastric losses with H2 blockers, or cessation of diuretic use. Additional interventions should include saline repletion and KCl administration as appropriate. The effectiveness of these therapies can be followed by measuring urine pH, which should rise to greater than 7 because volume and Cl repletion is sufficient to promote HCO3 excretion. Plasma (HCO3 ) and arterial pH will fall as the generational forces are interrupted and excess HCO3 is eliminated. The urine (Cl) will not rise until the Cl deficit is repaired.
If edema, heart failure, hepatic cirrhosis, or nephrosis are issues but the pathophysiology clearly involves a reduction in effective intravascular volume, then administration of saline is contraindicated. Administration of KCl remains very important to replete Cl in these situations. (74) (118) Acetazolamide, 250 to 500 mg every 12 to 24 hours, may be employed if diuresis is essential. Acetazolamide will promote an NaHCO3 diuresis, and this will usually effectively turn a metabolic alkalosis around. However, the physician must be aware that urinary K losses can be very high with acetazolamide and effective arterial volume will decline. This may actually aggravate the underlying pathophysiology responsible for maintenance of the alkalosis. In these instances, acetazolamide use must be titrated carefully and used in concert with extra KCl administration to maintain a relatively high plasma (Cl). K-sparing diuretics such as spironolactone, amiloride, or triamterene may be useful in these contexts as well. Colloid therapy may improve effective arterial circulation in cirrhosis or nephrosis and should be employed carefully.
Severe alkalemia may necessitate hydrochloric acid administration. (1) (24) (82) (137) (140) Hydrochloric acid can be prepared as an isotonic fluid (0.15N or 150 mEq/L) and administered into a central vein. The quantity required to return plasma (HCO3 ) to normal equals the calculated HCO3 excess in milliequivalents, which is estimated from the same formula used to estimate the HCO3 deficit in the context of a metabolic acidosis: Total body HCO3 excess (mEq) = HCO3 distribution space (L) × Plasma HCO3 excess (mEq/L) Recall that the HCO3 distribution space is 50% lean body mass. Therefore the formula becomes Total body HCO3 excess (mEq) = 0.5 × Lean body weight (kg = L) × (Plasma (HCO3 ) - 24 (mEq/L) A 0.15N solution of HCl contains 150 mEq/L of HCl. The requisite amount HCl in milliequivalents should be calculated as that amount required to eliminate the total body HCO3 excess. The HCl solution should be infused at a rate of 50 to 100 mL/hr. If the total body HCO3 excess is calculated as 100 mEq, for example, then 667 mL of 0.15N HCl would correct the base excess, assuming that no new alkali was added to the body fluids during the time it took to infuse the solution. Complete correction may not be necessary. Arterial pH and plasma (Cl) and (HCO3 ) should be monitored every
Very rarely, a patient with severe metabolic alkalemia (arterial pH greater than 7.65) will require emergent correction of the alkalemia because of malignant cardiac arrhythmias or convulsions. Then one cannot wait to constitute a hydrochloric acid infusion, which may take 1 to 2 hours in a busy pharmacy, and intubation with heavy sedation or muscle paralysis and deliberate hypoventilation might be the only way to bring the pH to a safe range quickly. Intubation and mechanical hypoventilation do not resolve the underlying alkalosis or alter the underlying pathophysiology. One simply forces a respiratory acidosis onto the patient to lower pH while other interventions are arranged and commenced. In fact, raising the PCO2 will further stimulate renal HCO3 retention and generation. Hydrochloric acid should still be administered if one must resort to intubation and a forced respiratory acidosis, as should other maneuvers that correct the responsible pathogenetic factors.
Arginine HCl and ammonium chloride infusions have been investigated as alternatives to pure HCl infusion. (118) Although effective, arginine HCl predictably promotes hyperkalemia through a transcellular shift of K, which can aggravate arrhythmias. (118) For this reason it is not recommended. Ammonium chloride is contraindicated in patients with liver disease and has even provoked an ammonium-associated encephalopathy in patients with apparently normal liver function. Pure HCl is probably the better alternative to both of these when NaCl and KCl are insufficient alone. Low bicarbonate-based hemodialysis or bicarbonate-free peritoneal dialysis may be employed to remove HCO3 . These modalities can be quite effective. Hemodialysis is more efficient in this regard but hemodynamically more stressful. If either is employed, one must take care to not K-deplete the patient.
Repair of a hypervolemic chloride-expanded alkalosis hinges on K repletion and correction of the mineralocorticoid excess. (53) (74) (118) Potassium repletion is not easily achieved inasmuch as renal K losses can be persistently high unless the mineralocorticoid excess is controlled. One should measure 24-hour urinary K losses to gauge replacement needs. K-sparing diuretics are very useful in these patients. Ultimate correction of this type of metabolic alkalosis may require surgery for an adrenal adenoma or chronic prescription of the aldosterone antagonist spironolactone. Spironolactone, amiloride, or triamterene plus KCl is usually effective for those patients in whom surgery is contraindicated or deemed elective.
A respiratory alkalosis denotes a process caused by primary hyperventilation with resultant reductions in arterial PCO2 . Arterial pH thereby rises above normal. Respiratory alkalosis is probably the most common acid-base disorder because of the multitude of events or conditions that promote hyperventilation. (101) (120)
As with metabolic alkalosis, buffers are called into play to mitigate pH swings. Proteins and hemoglobin are principally involved; they release H ions that move into plasma and bind with HCO3 , thus lowering its concentration. (113) (120)
There is no respiratory response to a primary respiratory alkalosis since the primary drive to hyperventilation overrides the suppressing effect that an alkalemic pH would normally have on the respiratory center.
The renal response to a respiratory alkalosis is very important. Unfortunately, it is rather slow. (34) (120) Persistent hypocapnia results in HCO3 loss in the urine, which mitigates the pH increase caused by the hypocapnia. Bicarbonaturia is detectable within 2 to 3 hours of the onset of a respiratory alkalosis but does not reach maximum compensation for 2 to 3 days. Reduced HCO3 reabsorption results from reduced renal H secretion, which mechanistically results from a rise in cell pH. Also associated with the rise in cell pH is a reduction in renal NH3 synthesis. Decreased urinary ammonium excretion results and diminishes overall renal acid excretion. Retained H mitigates alkalemia directly, helps reduce plasma (HCO3 ), and contributes to CO2 production. (120) These latter occurrences mitigate alkalemia indirectly through the Henderson-Hasselbalch relationship. For each 10-mm Hg decrement in PCO2 , one should expect a 5-mEq/L reduction in plasma (HCO3 ).
A primary respiratory alkalosis evolves fundamentally from alveolar hyperventilation. Indirect or direct stimulation of the CNS respiratory center is a central feature. Causes include hypoxemia, various neurologic disorders that directly stimulate the central respiratory center, acute and chronic pulmonary parenchymal diseases, pulmonary edema, and iatrogenic overventilation with a mechanical ventilator (Table 34-18) . In the critical care setting, sepsis or liver failure are the most common causes of respiratory alkalosis. The common denominator among all of these causes is a heightened respiratory drive, which has its genesis in either oxygen deficit, central stimulation, or some sort of pulmonary irritation. (120)
Diagnosis rests on the measurement of arterial pH, PCO2 , and (HCO3 ). Arterial PCO2 is low and pH high. If the alkalosis is acute, plasma (HCO3 ) may not yet be substantially reduced. The renal response will take several hours to evolve. In fact, the plasma (HCO3 ) can be used as a gauge to chronicity. If the respiratory alkalosis has been present for more than 8 to 12 hours, plasma (HCO3 ) should be measurably reduced and the urine pH alkaline. Maximum lowering of plasma (HCO3 ) takes 36 to 72 hours. A chronic stead-state alkalosis is recognized when the plasma (HCO3 ) remains at a stable level in spite of persisting hypocapnia. (120) This level is typically 16 to 18 mEq/L. Chronic respiratory alkalosis with renal compensation might be misdiagnosed as a hyperchloremic acidosis
Once the presence of a respiratory alkalosis is documented, the underlying cause should be sought. It is important to realize that a respiratory alkalosis often exists in association with a serious underlying disease or intoxication. Such underlying disorders are usually evident through analysis of the medical history, physical examination, chest or brain radiographs, and laboratory testing (Table 34-18) .
The threat of respiratory alkalosis derives more from the underlying disorder than from hypocapnia or its associated alkalemia. Nevertheless, some adverse consequences can emerge from severe hypocapnia. (92) (95) (107) Cerebral blood flow is reduced almost 20% by acute hypocapnia, and this can cause light-headedness, syncope, confusion, and even transient convulsions. Cardiovascular changes also emerge. Hyperventilation and hypocapnia in anesthetized or paralyzed patients decrease cardiac output and arterial blood pressure. In patients with known coronary disease, respiratory alkalosis may cause atrial and ventricular arrhythmias. Lactic acid production increases with acute respiratory alkalosis, but this does not persist with sustained hypocapnia. Serum phosphate levels can drop dramatically with acute respiratory alkalosis, particularly if the patient is receiving a glucose or insulin infusion. This occurs because of increased cell uptake of phosphate. Plasma potassium levels can also decline as a result of increased cell uptake, but this is of smaller magnitude than the serum phosphate decline.
Although the alkalemic and hypocapnic threats are of concern, treatment should be aimed primarily at the cause because clinical morbidity results primarily from the underlying problem that is driving hyperventilation, such as sepsis or liver failure. Treatment aimed at the pH itself, such as rebreathing expired air or deliberately enriching oxygen supplies with carbon dioxide, has proved either futile or even more irritating to the patient. (120)
Respiratory acidosis is that acid-base disturbance that results from primary alveolar hypoventilation and an increase in arterial PCO2 . The primary rise in PCO2 causes arterial pH to fall. Overproduction of CO2 may coexist with alveolar hypoventilation in some special circumstances, but it is never the sole explanation for a respiratory acidosis because a normal respiratory system is typically stimulated by accumulations in CO2 . (119)
Primary elevations in arterial PCO2 acidify the body fluids because of the production of carbonic acid. (113) (119) A slight increment in plasma (HCO3 ) appears within minutes of the onset of hypercapnia acidemia. (113) (119) It appears that this bicarbonate is derived from nonbicarbonate buffering reactions with proteins, phosphate, and hemoglobin. As free H split off from carbonic acid is taken up by these molecules, HCO3 is left behind. Thus, dual benefit is achieved as free H is buffered and new HCO3 is produced. The former attenuates pH decline directly, whereas the latter attenuates the pH decline indirectly according to the Henderson-Hasselbalch relationship.
The normal respiratory response to hypercapnia is a stimulation in ventilation. This drive is powerful. However, respiratory acidosis evolves fundamentally because of a defect in this drive or its execution.
The renal response to a respiratory acidosis is critical, although relatively slow to develop. (34) (100) (119) The renal response involves an increase in proximal HCO3 reabsorption and an elevation in distal H secretion and HCO3 generation. Thus new HCO3 is produced by the kidney and then retained by virtue of the alteration in proximal HCO3 reabsorption kinetics. Both responses are probably brought about by increased intracellular PCO2 and an associated intracellular acidosis. Intracellular acidosis stimulates both proximal tubular Na/H exchange and distal tubular H-ATPase secretion with concomitant new HCO3 production. In the setting of a steady-state chronic respiratory acidosis, one should expect a 3- to 4-mEq/L increment in plasma (HCO3 ) for every 10-mm Hg rise in PCO2 .
Any process resulting in alveolar hypoventilation can produce hypercapnia and respiratory acidosis. These include a diminished CNS respiratory drive, weakened chest wall muscles or restrictive chest wall defects with compromised chest wall movement, upper airway obstruction or bronchiolar obstruction with air trapping, obstructed gas exchange at the alveoli, and iatrogenic mechanical underventilation (Table 34-19) . Hypercapnia results because perfused alveoli, which receive CO2 from venous blood, cannot effectively expire the CO2 . Acidemia then results because accumulating
Acute hypercapnia may result in a medical emergency because the renal response is sluggish and hypoxemia typically coexists. In this context, therapy must be directed toward the root cause of the hypoventilation. If this is judged to be of little help, then prompt intubation and mechanical ventilation are indicated.
Therapy for chronic respiratory acidosis also calls for reversal or amelioration of the root causes, but this is usually of incomplete benefit because of the chronic nature of the underlying problem. Often the clinician faces the problem of an acute respiratory acidosis superimposed on a chronic respiratory acidosis. Here, one s therapeutic objective would be to reverse the acute problem and bring the patient back to the compensated state of his chronic respiratory acidosis. (74) (100)
A therapeutic pitfall in the treatment of a respiratory acidosis is the creation of a posthypercapnic alkalosis. (24) (74) (92) This arises when a patient with a properly compensated chronic respiratory acidosis is treated so that hypercapnia is completely eliminated and the patient is left with a high plasma (HCO3 ) but a normal or near-normal PCO2 . A frank alkalemia results. Renal excretion of the elevated HCO3 takes hours and may not occur at all if hypovolemia or hypokalemia coexists or if electrolyte administration is relatively chloride deficient. The usual context for this occurrence is a patient with chronic respiratory acidosis who experiences an acute respiratory decompensation resulting in a steep rise in the PCO2 that requires intubation. (92) With mechanical ventilation, the elevated PCO2 can be easily lowered to normal, but excretion of HCO3 will lag by many hours. An isolated elevation in plasma (HCO3 ) results. For this reason, one should not correct the hypercapnia of a decompensated chronic respiratory acidosis either rapidly or fully. Additionally, one should take care to ensure that all chloride and potassium deficits are restored and effective circulating blood volume optimized. Emergence of a metabolic alkalosis while one is attempting to repair a respiratory acidosis can impair weaning attempts by blunting the respiratory drive, so prevention of this problem requires particular vigilance. Hydrochloric acid infusion and acetazolamide administration have been presented as therapeutic interventions for posthypercapnic alkalosis or when a metabolic alkalosis evolves as an additional primary disturbance complicating a primary respiratory acidosis. (24) (68) These interventions can be effective, but their employment must be with extreme caution and only with firm indication. Neither should be employed when the pH is subnormal or in the low-normal range. An acidemia will surely emerge. They should only be used to treat an alkalemia. Additionally, the physician should realize that acetazolamide will cause large urinary K losses along with HCO3 losses. Potassium repletion must be ensured first, and K administration is usually necessary in the wake of an acetazolamide diuresis.
Finally, alkali therapy is virtually never indicated for respiratory acidosis. Although rational in the immediate sense, exogenous HCO3 will be converted to CO2 , potentially aggravating hypercapnia and intracellular acidosis since CO2 elimination is the fundamental problem. If arterial pH is below 7.00 and intubation with mechanical ventilation is under way, however, bicarbonate administration may be beneficial during those few minutes that it takes to accomplish intubation. (102) Proper therapy for respiratory acidosis first and foremost is improved ventilation of CO2 .
When the acidemia or alkalemia can be ascribed to a single pathophysiologic process, then the disturbance is referred to as a simple or primary acid-base disorder. (100) The compensatory response, if it is appropriate in direction and degree, is not a second disorder but simply the expected and desired physiologic compensation to the primary disturbance (Table 34-12) and (Table 34-20) .
However, two or more primary acid-base disturbances may actively coexist. Then a mixed acid-base disturbance truly exists. (92) (100) (113) The pH deviation may be extreme if, for example, a primary respiratory acidosis coexists with a primary metabolic acidosis. On the other hand, the pH deviation may be minimal if the coexisting primary disorders tend to drive the pH in opposite directions, such as when a primary metabolic acidosis coexists with a primary respiratory alkalosis or when a primary metabolic alkalosis coexists with a primary respiratory acidosis.
Compensatory responses are called into play from the pH deviation and can usually be predicted from an assessment of the primary acid-base disturbances in progress. However, what often underlies the evolution of a mixed acid-base disturbance is an excessive compensatory response or failure or inadequacy of the compensatory response. Accordingly, mixed acid-base disturbances are often first recognized and then diagnosed when the physician notes that compensatory responses are inappropriate or not as predicted. A clear understanding of appropriate compensations to primary acid-base disturbances is critical to the diagnosis of any mixed acid-base disorder (see the previous sections and Table 34-20 ).
For purposes of discussion, one can group the mixed acid-base
disorders into 4 basic categories
(Table 34-21)
. Failure
Effective treatment of mixed acid-base disorders depends on correct identification of the pathophysiologic processes driving each component disturbance and diagnosis of the dominant process or processes. A correct diagnosis can be difficult. It requires a systematic approach that is outlined in the final section of this chapter. Once component pathophysiologic
Respiratory acidosis and metabolic acidosis often coexist in the context of cardiopulmonary failure or arrest. Metabolic acidosis evolves from tissue hypoperfusion and respiratory acidosis evolves from profound alveolar hypoventilation. Because hypercapnia coexists with low serum (HCO3 ), severe acidemia is a major threat. Hypoxemia and organ ischemia are equally troubling threats.
This mixed disorder may evolve when a patient with chronic obstructive lung disease evolves a metabolic acidosis for any reason such as diarrhea, ketoacidosis, or lactic acidosis or when a patient with a primary metabolic acidosis evolves respiratory failure for any reason. Intoxications with methanol, ethylene glycol, and ethanol may all be associated with mixed metabolic and respiratory acidosis if respiration is severely depressed.
Mixed metabolic and respiratory acidosis is recognized when a profoundly acidemic pH is associated with less profound reductions in plasma (HCO3 ) and PCO2 . In some circumstances, the mixed disorder comes to light because the expected respiratory compensation for a metabolic acidosis is inadequate or nonexistent. At other times, the mixed disturbance is discovered when a severe respiratory acidosis is accompanied by a low or normal plasma (HCO3 ) and an elevation in the plasma anion gap. Inasmuch as mixed disorders are common in critical care settings, the discipline of always computing expected compensations for primary acid-base disorders and calculating the plasma anion gap is critically important. Inappropriate compensations or unexpected elevations in the plasma anion gap are often the first clue that a mixed acid-base disturbance exists. (92) (100) Consulting an acid-base map is also helpful (Fig 34-19) (Figure Not Available) . (33)
Therapy must be directed at both disorders simultaneously. It is imperative that etiologic processes be identified so that therapy can be directed toward specific processes. It should be remembered that a respiratory acidosis is more rapidly repaired than a metabolic acidosis, so establishing effective ventilation can swiftly lift the pH out of a dangerous acidemic range. Since the respiratory acidosis exists as a primary disturbance, this may require rapid intubation and mechanical ventilation. Administration of NaHCO3 may gain a transient improvement in pH in the context of a mixed respiratory and metabolic acidosis, but as with other primary metabolic acidoses, interventions must primarily aim at interrupting the responsible pathogenetic processes. Furthermore, intravenous bicarbonate loading may worsen intracellular pH by increasing PCO2 , particularly if elimination of CO2 is impaired. Accordingly, intravenous bicarbonate must be used only when improvement in ventilation is simultaneously under way.
A combined respiratory and metabolic alkalosis is characterized by a marked alkalemic deviation in arterial pH coupled with a near-normal plasma (HCO3 ) and reduced PCO2 . As with combined respiratory and metabolic acidoses, coexisting respiratory and metabolic alkaloses are first suspected when the expected compensations for either primary disturbance are lacking or insufficient.
This mixed disorder can evolve in patients with hepatic cirrhosis and an associated primary respiratory alkalosis who are given loop or thiazide diuretics or who vomit or lose gastric HCl through nasogastric suction. It may also be seen when a hyperventilating patient is vomiting or receiving nasogastric suction. Common contexts are a trauma victim with pain and visceral or cranial injury or a pregnant woman with hyperemesis gravidarum. A mixed metabolic and respiratory alkalosis may also evolve iatrogenically in a patient with a chronic primary respiratory acidosis who is intubated and rapidly ventilated to hypocapnic or normocapnic levels. Since plasma (HCO3 ) is normally elevated in this context as a compensation to the chronic respiratory acidosis, a rapid reduction in PCO2 will produce a severe alkalemia. This is referred to as a posthypercapnic alkalosis. As stated, plasma (HCO3 ) is left elevated while PCO2 is reduced to a relative alkalemic range. This disorder is properly viewed as a mixed disorder because the two components of the Henderson-Hasselbalch acid-base ratio ((HCO3 ) and PCO2 ) are moving simultaneously in opposite directions.
Correction of iatrogenic hyperventilation is the first objective of therapy when a posthypercapnic alkalosis is recognized. Even better is to prevent such an occurrence. When correcting severe hypercapnia that complicates a chronic respiratory acidosis, PCO2 should be reduced to a mildly hypercapnic range. The physician should be mindful that it is the (HCO3 )/PCO2 ratio that determines pH, not one value alone. If PCO2 is normalized while plasma (HCO3 ) remains elevated, then an alkalosis will result.
When metabolic alkalosis evolves to complicate a primary respiratory alkalosis, as with liver disease or trauma and nasogastric suction, correction of the metabolic alkalosis with saline and KCl as tolerated is the first priority. If these interventions are ineffective or contraindicated because of total body fluid overload, then acetazolamide might be employed to promote HCO3 excretion and reduce arterial pH. (94) Two caveats are in order regarding acetazolamide use: (1) acetazolamide promotes HCO3 excretion and will lower arterial pH. If the arterial pH is normal, bicarbonaturia will result in an acidemia; thus acetazolamide should be used only when an alkalemia exists; (2) By promoting bicarbonaturia, large quantities of Na and K are usually lost; K depletion is thereby a complication. Likewise, Na and volume depletion are also concerns because loss of these cations may aggravate the underlying pathophysiologic forces that created the metabolic alkalosis in the first place.
Mixed respiratory acidosis with metabolic alkalosis is characterized chemically by a normal or near-normal pH coupled with unexpectedly elevated plasma (HCO3 ) and PCO2 . It is recognized when the expected compensations for either disorder seem exaggerated and result in a normal arterial pH. (92)
The combination of a primary respiratory acidosis and metabolic alkalosis is seen most commonly in patients with
Figure R34-19 (Figure Not Available) Acid-base nomogram. This nomogram relates arterial pH to arterial (HCO3
)
and PCO2
. Simple acid-base disturbances
fall within the bold confidence bands. If the pH, (HCO3
), and
PCO2
are plotted and fall outside the bold confidence
bands, then a mixed acid-base disorder exists. This nomogram facilitates
recognition of mixed acid-base disorders.
(From Cogan
MG, Rector FC Jr: Acid-base disorders, in Brenner BM, Rector FC Jr
(eds): The Kidney. Philadelphia, WB Saunders, 1986, pp
457-518. Used by permission.)
A primary respiratory acidosis only rarely complicates an already existing primary metabolic alkalosis. This may occur if a patient requiring nasogastric suction is given excessive sedation and respiration becomes impaired or if such a patient becomes profoundly K depleted and experiences respiratory muscle weakness.
Therapy for this mixed disorder should be aimed at each primary disorder. Plasma (K) and intravascular volume should be repleted as appropriate. Adequate chloride must be given. If the diuresis that resulted in the alkalosis was desirable, as is sometimes the case when congestive heart failure complicates the lung disease, then KCl with acetazolamide
Combined respiratory alkalosis with metabolic acidosis is characterized by a near-normal pH but surprisingly low PCO2 and plasma (HCO3 ). Coexistence of these disorders as two primary disorders is suspected when calculation of the expected respiratory compensation for a metabolic acidosis reveals excessive compensation or when a normal pH is uncovered in the context of a primary metabolic acidosis or respiratory alkalosis. (92)
The combination of respiratory alkalosis and metabolic acidosis is seen in sepsis, advanced liver disease with lactic acidosis, and salicylate poisoning and when renal insufficiency is complicated by congestive heart failure or pneumonia such that hyperventilation and hypocapnia result.
Diagnosis of the etiologic processes is essential for proper therapy, for one s interventions should be directed at the underlying disorders rather than the pH itself.
Metabolic acidosis and alkalosis may coexist as separate and distinct processes that occur either simultaneously or sequentially and generate opposing effects on plasma (HCO3 ) and pH. (92) (100) The change in pH and plasma (HCO3 ) will reflect the dominant process. Concomitant metabolic alkalosis and acidosis should be suspected when an increment in the plasma anion gap is greater than the decrement in plasma (HCO3 ). Examples include uremia or ketoacidosis with vomiting or nasogastric suctioning, diuretic use and lactic acidosis, or vomiting with an abdominal crisis such as bowel infarction that results in a lactic acidosis.
Therapy should be directed at the underlying disorders. Care must be taken to correct both etiologic processes more or less simultaneously so that one disorder does not emerge as a singular disorder, which would produce profound pH changes.
A triple acid-base disorder can emerge when three primary processes act to alter pH, PCO2 , and plasma (HCO3 ). (100) This would pertain when a primary respiratory disturbance becomes superimposed on a mixed metabolic acidosis and alkalosis. By definition, it is not possible to have a mixed respiratory acidosis and alkalosis, so the triple disturbance must contain the two metabolic disturbances with a superimposed primary respiratory disturbance. One example would be the following: (1) a primary metabolic alkalosis develops from vomiting; (2) this is followed by a metabolic acidosis caused by progressive renal failure or a lactic acidosis; (3) then a respiratory disturbance emerges such as respiratory failure.
Triple disturbances are sometimes seen when a patient has a chronic acid-base disturbance such as chronic respiratory acidosis or chronic renal acidosis and then evolves another superimposed mixed disturbance.
Therapy for triple disorders requires careful identification of the components and their respective pathogenesis. Then intervention should be directed simultaneously to the components and their pathophysiology with the intention of primary interruption of each component. Care must be taken to avoid asynchronous correction of the components so as to avoid large swings in blood pH.
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