The body’s handling of hydrogen ion (H+) is a particularly complex example of electrolyte management, as it involves not only dietary intake and renal clearance but also extracellular and intracellular buffer systems and respiratory as well as renal excretion.
An acid is a chemical that donates a H+ in solution, for example, HCl or H2CO3. A base is a chemical that accepts H+ in solution, for example, Cl− or HCO3−. The concentration of H+ in a solution determines the acidity of the solution. Acidity of a solution is measured by pH, which is the negative logarithm of H+ concentration expressed in mol/L. The strength of an acid is determined by its degree of dissociation into H+ and the corresponding base, as expressed in the Henderson-Hasselbalch (H-H) equation:
where K = dissociation constant, [A−] = concentration of acid, [HA] = concentration of base. Stronger acids have a higher K than weaker acids.
The main buffer system in human blood is a carbonic acid/bicarbonate (H2CO3/HCO3−) system. Using the H-H equation, the pH of this buffer system is calculated as:
pH = pK × log [HCO3−]/[H2CO3]
H2CO3 in the blood exists mostly as CO2 (the so-called “volatile acid”); conversion of one to the other is catalyzed by the enzyme carbonic anhydrase. The dissociation constant of CO2 is 0.03. Making these substitutions into the equation, we have:
pH = pK × log [HCO3−]/[pCO2 × 0.03]
where Pco2 is the partial pressure of CO2. The pK for this buffer system is 6.1. In arterial blood, HCO3− normally ranges from 21 to 37 mmol/L, while Pco2 ranges from 36 to 44 mm Hg. Thus, arterial pH normally ranges from 7.36 to 7.44. Venous blood is easier to sample than arterial blood (Table 9–2). Venous blood gas sampling varies significantly between institutions, and between central, mixed, and different peripheral sites of sampling, and thus must be interpreted with caution.
Table 9–2.Estimated arterial to venous blood gas conversions. ||Download (.pdf) Table 9–2. Estimated arterial to venous blood gas conversions.
|pHa = pHv × 1.005 |
|Paco2 = Pvco2 × 0.8 |
|HCO3−a = HCO3−v × 0.90 |
Acid-base homeostasis is maintained by pulmonary excretion of CO2 and renal excretion of nonvolatile acids, which is discussed in further sections.
The fundamental acid-base disorders are:
Acidemia: pH below the normal range
Alkalemia: pH above the normal range
Acidosis: a process that lowers the pH of the extracellular fluid
Alkalosis: a process that raises the pH of the extracellular fluid
There are four primary or simple (as opposed to mixed) acid-base disorders:
Metabolic acidosis: a disorder in which decreased HCO3− causes decreased pH
Metabolic alkalosis: a disorder in which increased HCO3− causes increased pH
Respiratory acidosis: a disorder in which increased Pco2 causes decreased pH
Respiratory alkalosis: a disorder in which decreased Pco2 increased pH are found
Acid-base disorders are classified as simple or mixed. In a simple acid-base disorder, only one primary acid-base disorder is present, and the compensatory response is appropriate. In a mixed acid-base disorder, more than one primary acid-base disorder is present. Mixed acid-base disorders are suspected from a patient’s history, from a lesser or greater than expected compensatory response, and from analysis of the serum electrolytes and anion gap (AG) (see below).
The use of a systematic approach to identifying and diagnosing acid-base disorders is essential. One must first determine alkalemia or academia based on pH. One must then determine whether a metabolic derangement with respiratory compensation or a respiratory derangement with metabolic compensation exists, based on the HCO3− and Pco2 values (Table 9–3).
Table 9–3.Changes in HCO3− and pCO2 in primary acid-base disorders. ||Download (.pdf) Table 9–3. Changes in HCO3− and pCO2 in primary acid-base disorders.
|Disorder ||pH ||HCO3− ||Pco2 |
|Metabolic acidosis ||⇓ ||⇓ ||⇓ (compensatory) |
|Metabolic alkalosis ||⇑ ||⇑ ||⇑ (compensatory) |
|Respiratory acidosis ||⇓ ||⇑ (compensatory) ||⇑ |
|Respiratory alkalosis ||⇑ ||⇓ (compensatory) ||⇓ |
Whether the disturbance is primarily respiratory or metabolic, some degree of compensatory change occurs in an attempt to maintain normal pH. Changes in Pco2 (respiratory disorders) are compensated for by changes in HCO3− (metabolic/renal compensation), and vice versa.
Acute respiratory disorders may develop in matter of moments. Such circumstances may not allow sufficient time for renal compensation, resulting in severe pH changes without significant compensatory changes. By contrast, chronic respiratory disturbances allow the full range of renal compensatory mechanisms to function. In these circumstances, pH may remain normal or nearly normal despite wide variations in Pco2. By contrast, respiratory compensation for metabolic disorders occurs quickly. Thus there is little difference in respiratory compensation for acute and chronic metabolic disorders.
Metabolic acidosis is caused by increased production of H+ or by excessive loss of HCO3−. In the surgical setting, metabolic acidosis is commonly encountered in trauma, critically ill, and postoperative patients, and especially in patients in shock.
The serum AG is vital to determining the cause of any metabolic acidosis. AG may help differentiate between metabolic acidosis caused by accumulation of acid and that caused by loss of HCO3−.
AG represents the difference between the primary measured serum cation, Na+, and the primary measured serum anions, Cl− and HCO3−:
The AG is normally less than 12; however, the highest normal value varies by institution.
Increased acid production causes an increased AG, as unmeasured anions electrically neutralize Na+. Thus metabolic acidosis caused by increased H+ production is associated with a high AG. The most common causes of an AG metabolic acidosis include methanol ingestion, uremia/renal failure, diabetic ketoacidosis, polypropylene glycol ingestion, isoniazid ingestion, lactic acidosis, ethylene glycol ingestion, and salicylate poisoning. In the surgical setting lactic acidosis is by far the most common cause, seen in hypoperfused states like shock and sepsis.
A non-AG metabolic acidosis is caused by excessive HCO3 loss. The nephron maintains electrical neutrality by reabsorbing Cl− as HCO3− is lost, hence the normal AG. Non-AG metabolic acidosis in the surgical setting typically results from diarrhea or high small bowel output, for example, from an ileostomy. Non-AG acidosis also occurs in renal tubular acidosis, as the nephron fails to reabsorb HCO3−. Iatrogenic hyperchloremia, especially from administration of large amounts of normal saline to trauma and postoperative patients, may induce a non-AG metabolic acidosis.
The AG may be influenced by phenomena unrelated to acid-base balance, which must be kept in mind. Hypoalbuminemia may lower AG, as Cl− and HCO3− increase to electrically balance Na+ which was previously balanced by albumin. Similarly, hyper- or hypostates of positively charged ions like calcium, magnesium, and potassium may affect the AG.
Treatment of metabolic acidosis involves identifying the underlying cause of the acidosis and correcting it. Often, this is sufficient. If this is not sufficient, correction may require administration of exogenous alkali in the form of NaHCO3− to correct the derangement in pH. The degree of restoration is estimated by subtracting the plasma HCO3− from the normal value (24 mmol/L at our institution) and multiplying the resulting number by half TBW. This is a useful empiric formula, as in practice it is unwise (and unnecessary) to administer enough NaHCO3− to completely correct pH. Doing so will likely cause fluid overload from the large Na+ load delivered, and will likely overcorrect the acidosis. In patients with a chronic metabolic acidosis, often seen in chronic renal failure, alkali may be administered chronically as oral NaHCO3−. Efforts to minimize the magnitude of HCO3− loss in these patients must be undertaken as well.
The body’s response to metabolic acidosis is respiratory hyperventilation, “blowing off” H2CO3 as CO2 and correcting the acidosis. This response is rapid, beginning within 30 minutes of the onset of acidosis and reaching full compensation within 24 hours. The adequacy of the respiratory response to metabolic acidosis is evaluated using Winter’s formula:
Pco2 = (1.5 × HCO3− in mmol/L) + (8 ± 2)
If compensation is inadequate or excessive—that is, if Pco2 is not within the range predicted by Winter’s formula—one must evaluate for a mixed acid-base disorder (see below).
Metabolic alkalosis is often encountered in surgical patients. The pathogenesis is complex, but often involves:
Loss of H+, usually via gastric losses of HCl
Total body K+ depletion
All three are commonly encountered with vomiting or gastric suctioning, diuretic use, and renal failure.
HCl is secreted by chief cells in the gastric mucosa; simultaneously, HCO3− is absorbed in the blood. NaHCO3 is then secreted by the pancreas into the lumen of the duodenum, neutralizing the gastric acid, after which the neutralized acid and base are reabsorbed by the small intestine. Thus, under normal circumstances there is no net alteration of acid-base balance in the function of the gastrointestinal tract. However, when H+ is lost from the gastric lumen, for example, through emesis, gastric suctioning or gastric drainage—the result is loss of H+ from the gastric lumen and a corresponding gain of HCO3− in the blood, leading to metabolic alkalosis.
Normally, the kidneys excrete excess HCO3−; however, if volume depletion accompanies HCO3− excess, the kidneys attempt to maintain normovolemia by increasing tubular reabsorption of Na+, which is reabsorbed in an electrically neutral fashion by increasing reabsorption of Cl− and HCO3−. This impairs HCO3− excretion, perpetuating the metabolic alkalosis.
Severe K+ depletion further exacerbates metabolic alkalosis. To preserve K+, Na+ is exchanged for H+ in the kidney, through the Na+-K+ and Na+-H+ ATPases in the distal renal tubule. This explains why severe metabolic alkalosis with hypokalemia results in paradoxical aciduria. In such cases, urine Na+, K+, and Cl− concentrations are low, and the urine is acidic. In simple volume depletion, urine Cl− alone is low and the urine is alkaline. Severe metabolic alkalosis may lead to tetany and seizures, as seen in hypokalemia and hypocalcemia.
Treatment of metabolic alkalosis includes fluid administration, usually normal saline. With adequate fluid repletion, tubular reabsorption of Na+ is diminished, and the kidneys will excrete excess HCO3−. K+ must be repleted, both to allow for correction of the alkalosis and to prevent life-threatening hypokalemia. Repletion of volume with normal saline and of potassium with KCl also provides the nephron with needed Cl−, allowing for reabsorption of K+ and Na+ with Cl− instead of HCO3−. Acetazolamide, a carbonic anhydrase inhibitor diuretic, may also be used to treat metabolic alkalosis as long as the patient is euvolemic. Administration of exogenous acid in the form of HCl may be employed in the case of profound alkalosis.
Adequate respiratory compensation for metabolic alkalosis should raise Pco2 by 0.7 mm Hg for every 1 mmol/L elevation in HCO3−. Generally, respiratory compensation will not raise Pco2 beyond 55 mm Hg. Thus a Pco2 greater than 60 mm Hg in the setting of metabolic alkalosis suggests a mixed metabolic alkalosis and respiratory acidosis.
Acute respiratory acidosis occurs when ventilation suddenly becomes inadequate. CO2 accumulates in the blood, and as carbonic anhydrase coverts it to H2CO3, acidosis develops.
Acute respiratory acidosis is most common in conditions where gas exchange is physically impaired, resulting in decreased ventilation. These conditions typically involve decreased oxygenation as well. They include respiratory arrest, acute airway obstruction, pulmonary edema, pneumonia, saddle pulmonary embolus, aspiration of intraoral contents, and acute respiratory distress syndrome. Hypoventilation may occur in patients postoperatively who are oversedated (eg, from narcotics, benzodiazepines, or as they recover from general anesthesia). Pain, especially from large abdominal incisions or from rib fractures, leads to respiratory splinting and hypoventilation. Excess ethanol ingestion decreases respiratory drive, thereby impairing ventilation. Head trauma, either by direct damage to central nervous system respiratory centers or by global brain damage and brainstem herniation, may impair ventilation.
Patients with obesity hypoventilation syndrome and obstructive sleep apnea may develop a periodically recurring acute respiratory acidosis, leading eventually to some renal compensation. True chronic respiratory acidosis arises from chronic respiratory failure in which impaired ventilation leads to persistently elevated Pco2, for example, as seen in chronic obstructive pulmonary disease. Chronic respiratory acidosis is usually well tolerated with adequate renal compensation, thus pH may be normal or near normal.
Treatment of respiratory acidosis involves restoration of adequate ventilation by treating the underlying cause. Aggressive chest physical therapy and pulmonary toilet should be instituted on all postsurgical patients. Patients with pulmonary edema should receive appropriate diuretic therapy, and patients with pneumonia should receive appropriate antibiosis. Naloxone or flumazenil should be used as needed in the setting of narcotic or benzodiazepine overdose, respectively. If necessary, endotracheal intubation and mechanical ventilation should be employed in order to correct pCO2.
Acute respiratory acidosis should be corrected rapidly. However, too rapid correction of chronic respiratory acidosis risks causing posthypercapnic metabolic alkalosis syndrome, characterized by muscle spasms and by potentially lethal cardiac arrhythmias.
Over 80% of increased acid produced in respiratory acidosis is buffered by the body’s tissues and intracellular hemoglobin. The remaining minority is buffered by HCO3− in the blood, which the kidney reclaims and reabsorbs. Thus, metabolic (renal) compensation for respiratory disorders is a much slower process than respiratory compensation for metabolic disorders. Furthermore, in acute respiratory acidosis renal mechanisms may not have had time to function at all, and HCO3− may be within normal limits. Adequate renal compensation for respiratory acidosis involves an increase in HCO3− of 1 mmol/L for every 10 mm Hg increase in Pco2.
Hyperventilation decreases Pco2 (hypocapnia), leading to a respiratory alkalosis. In the surgical setting, anxiety, agitation, and pain are common causes of respiratory alkalosis. Hyperventilation and respiratory alkalosis may be an early sign of sepsis and of moderate pulmonary embolism. Chronic respiratory alkalosis occurs in chronic pulmonary and liver disease.
Acute respiratory alkalosis is treated by addressing the underlying cause. Patients may require pain control, sedation/anxiolytics, and even paralyzation and mechanical ventilation if necessary. Well-compensated chronic respiratory alkalosis does not require treatment. In these cases, rapid correction of pCO2 leads to so-called posthypocapnic hyperchloremic metabolic acidosis, which is often severe.
The renal response to respiratory alkalosis is decreased reabsorption of filtered HCO3−and increased urinary HCO3− excretion. HCO3− decreases as Cl− increases, since Na+ is reabsorbed with Cl− instead of with HCO3−. This same pattern is seen in hyperchloremic metabolic acidosis; the two are distinguished only by pH measurements.
Adequate renal compensation for respiratory alkalosis involves a decrease in HCO3− of 2 mmol/L for every 10 mm Hg decrease in Pco2.
Mixed Acid-Base Disorders
Many common pathophysiologic processes cause mixed acid-base disorders. In these situations, pH may be normal or near normal, but compensatory changes are either inadequate or exaggerated. One way of determining the presence of a simple versus mixed disorder is to plot the patient’s acid-base disorder on a nomogram (Figure 9–2). If the set of data falls outside one of the confidence bands, then by definition the patient has a mixed disorder. If the acid-base data falls within one of the confidence bands, the patient more likely has a simple acid-base disorder.
Acid-base nomogram for use in evaluation of clinical acid-base disorders. Hydrogen ion concentration (top) or blood pH (bottom) is plotted against plasma HCO3− concentration; curved lines are isopleths of CO2 tension (Paco2, mm Hg). Knowing any two of these variables permits estimation of the third. The circle in the center represents the range of normal values; the shaded bands represent the 95% confidence limits of four common acid-base disturbances: I, acute respiratory acidosis; II, acute respiratory alkalosis; III, chronic respiratory acidosis; IV, sustained metabolic acidosis. Points lying outside these shaded areas are mixed disturbances and indicate two primary acid-base disorders.
As with simple acid-base disorders, a systematic approach to mixed acid-base disorders is essential. First, determine the primary acid-base disorder. Next, determine whether or not adequate compensation has occurred, using the equations and rules given above (Table 9–4). If compensation is “inadequate,” meaning too little or too much, the patient has a mixed acid-base disorder.
Table 9−4.Expected compensation in primary acid-base disorders. ||Download (.pdf) Table 9−4. Expected compensation in primary acid-base disorders.
|Metabolic acidosis ||Winter’s formula: pCO2 = 1.5 × HCO3− + (8 ± 2) |
|Metabolic alkalosis ||⇑ Pco2 0.7 mm Hg for every 1 mmol/L increase in HCO3− |
|Respiratory acidosis ||⇑ HCO3− 1 mmol/L for every 10 mm Hg increase in Pco2 |
|Respiratory alkalosis ||⇓ HCO3− 2 mmol/L for every 10 mm Hg decrease in Pco2 |
An additional step is needed in the case of metabolic acidosis. After AG has been calculated, the “delta-delta” or “delta ratio” or “gap-gap” (three names for the same parameter) should be calculated:
where ΔΔ = delta-delta, ΔAG = AG − maximum normal AG, ΔHCO3− = normal HCO3− – HCO3−.
At our institution, maximum normal AG is 12 mmol/L and normal HCO3−concentration is 24 mmol/L, thus ΔΔ = (AG − 12)/(24 − HCO3−).
ΔΔ < 1 indicates the coexistence of an AG and a non-AG metabolic acidosis, that is, a metabolic acidosis caused by increased production of acid and by renal loss of HCO3−. This may occur in the setting of diabetic ketoacidosis.
ΔΔ > 1 indicates the coexistence of an AG metabolic acidosis and a metabolic alkalosis. This can occur in the intensive care unit in patients who have an underlying AG metabolic acidosis and are also undergoing diuresis or gastric suctioning, leading to the concurrent metabolic alkalosis.
The most common mixed acid-base disorder in surgical patients is a metabolic acidosis superimposed on a respiratory alkalosis. This occurs in patients with septic shock and hepatorenal syndrome, and also in the case of salicylate poisoning. Since the two acid-base disorders disrupt H+ homeostasis in opposite directions, the patient’s pH may be normal or near normal. Mixed respiratory acidosis and metabolic alkalosis is less common, occurring in the setting of cardiorespiratory arrest, which is a medical emergency.
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