Any etiology that limits the effective minute ventilation will result in decreased ventilation and in turn an increase in Pco2, leading to a respiratory acidosis. A list of possible causes of respiratory acidosis is shown in Table 21-3.
Table 21-3. Causes of Respiratory Acidosis ||Download (.pdf)
Table 21-3. Causes of Respiratory Acidosis
- CNS depression
- Chronic lung disease
- Neuromuscular disorders
- Acute airway obstruction
- Pulmonary edema
- Thoracic cage injury
- Hemothorax, pneumothorax
- Pleural effusion
- Mechanical ventilation
Treatment of a primary respiratory acidosis should be aimed at correcting the lack of respiratory drive, reducing the effective dead space, or increasing the minute ventilation. Remember that respiratory acidosis, if not the primary acid–base disorder, may be an appropriate compensation for a metabolic alkalosis! Make sure to rule out a mixed acid–base disorder before correcting it.
Respiratory alkalosis results from excessive minute ventilation and a resultant decrease in the Pco2. Potential causes of a respiratory alkalosis are shown in Table 21-4. Hypocapnic patients are not always alkalemic, and a respiratory alkalosis is a common compensation for metabolic acidosis. As in a respiratory acidosis, respiratory alkalosis may be an appropriate compensation, and caution should be entertained in ascribing a respiratory alkalosis to psychogenic hyperventilation until an underlying mixed acid–base disorder has been ruled out. Salicylate toxicity in particular can result in severe metabolic acidosis, and any treatment that removes or inhibits respiratory compensation, which can at times seem severe, may rapidly worsen the underlying acidemia.
Table 21-4. Causes of Respiratory Alkalosis ||Download (.pdf)
Table 21-4. Causes of Respiratory Alkalosis
- CNS disease
- Drug use—salicylates, catecholamines
- Hepatic encephalopathy
- Mechanical ventilation
Metabolic alkalosis is characterized by an increase in the [HCO3]. It is brought about by the excess loss of hydrogen ions, the endogenous administration of bicarbonate or another anion such as lactate, acetate, or citrate, or, most commonly, the increased reabsorption of bicarbonate.
A metabolic alkalosis is classified as chloride responsive or chloride resistant based on the spot urine chloride concentration. A chloride-responsive metabolic alkalosis presents with a low urinary chloride concentration of less than 15 mEq/L, suggesting total body chloride depletion and in turn renal retention of chloride. In order to maintain electrical neutrality, low [Cl−] is accompanied by a retention of HCO3−, and it is this retention of HCO3− that brings about the resultant alkalosis. As such, chloride-responsive metabolic alkalosis is more of a problem of chloride balance than of bicarbonate balance, and restoration of chloride is what is needed to allow the kidneys to normalize the [HCO3−] and in turn the alkalosis. Chloride-responsive metabolic alkaloses are due to gastrointestinal losses of chloride because of gastric suctioning (direct loss of hydrochloric acid [HCl]), volume depletion (reduction in space of distribution of HCO3−), or diuretic therapy (loss of NaCl and reduction in space of distribution of HCO3−).12 Chloride-responsive metabolic alkalosis is almost always associated with a volume deficit as well, and treatment should be aimed at correcting both the volume deficit and the chloride deficit, something which is most easily accomplished with normal saline (0.9% NaCl).13 The total deficit of chloride can be calculated according to the following equation:
The volume of saline, in liters to be infused, necessary to correct the chloride deficit can then be calculated by taking the chloride deficit and dividing by 154 mEq/L (the chloride concentration of normal saline). Infusion of dilute concentrations of HCl can also be utilized to replete both hydrogen ion and chloride stores in severe cases of chloride-responsive metabolic alkalosis, although normalization of volume status with isotonic saline is recommended first.
Chloride-resistant metabolic alkalosis is characterized by a high urinary spot chloride concentration greater then 25 mEq/L. It can be brought about by either mineralocorticoid excess or profound hypokalemia.
In a state of mineralocorticoid excess, such as Cushing's syndrome or excessive mineralocorticoid administration, the kidneys inappropriately retain HCO3− via an aldosterone-mediated pump in the proximal tubule. The workup should be aimed at identifying and correcting the underlying cause of the mineralocorticoid excess. Acetazolamide, by blocking carbonic anhydrase, can inhibit the reabsorption mechanism in the proximal tubule and help promote appropriate renal excretion of HCO3−, as well as facilitate diuresis of the fluid overload that typically accompanies this state.
Hypokalemia causes an intracellular shift of hydrogen ions resulting, by means of a shift of the bicarbonate buffering equation to the left, in a relative excess of HCO3−. In this case, repletion of potassium along with volume repletion, if required, should correct the alkalemia.
In all cases of metabolic alkalosis, careful consideration should be made to the potential exogenous sources of alkali in the patient's medications and fluids. Acetate, citrate, or lactate in parenteral infusions, blood transfusions, or IV fluids should be considered. One of the most common causes of metabolic alkalosis, as mentioned below, is an inadvertent “overshoot” metabolic alkalosis that results from overly aggressive or inappropriate administration of alkali as treatment for metabolic acidosis.
See Table 21-5 for a review of the common causes of metabolic alkalosis.
Table 21-5. Common Causes of Metabolic Alkalosis ||Download (.pdf)
Table 21-5. Common Causes of Metabolic Alkalosis
|Chloride-Responsive Urine, Cl <15 mEq/L||Chloride-Resistant Urine, Cl >25 mEq/L|
|Vomiting or gastric suction||Mineralocorticoid excess|
|Volume contraction||Licorice ingestion|
Metabolic acidosis is brought about due to the loss of extracellular bicarbonate (diarrhea, renal loss of bicarbonate, enterocuteneous fistulae), the accumulation of an endogenously produced organic acid (lactic acidosis, ketoacidosis), or the administration of an acid (salicylate, methanol, ethylene glycol, etc.).
The AG is utilized to evaluate patients with a metabolic acidosis. Metabolic acidosis can come about either due to an increase in hydrogen ion concentration or due to a loss of bicarbonate. The AG helps differentiate between these two possibilities.
The concept of electroneutrality dictates that the charge of all positively charged ions in the body must be matched by an equivalent charge of negatively charged ions. The AG is the difference between the total concentration of the predominant cation (Na+) and the total concentration of the predominant anions (Cl−, HCO3−):
The value of the AG represents the normal difference between the concentrations of cations and anions not included in the AG calculation. The cations and anions that normally contribute to the AG are shown in Table 21-6. Normal values for the AG vary slightly depending on the techniques of an individual lab. The original normal range for the AG was 8–16 mEq/L, although newer laboratory techniques have resulted in a lower normal range of 3–11 mEq/L.14 This value represents the value of the relative charge superiority of unmeasured anions relative to unmeasured cations.
Table 21-6. Unmeasured Ions Contributing to the Normal Anion Gap ||Download (.pdf)
Table 21-6. Unmeasured Ions Contributing to the Normal Anion Gap
|Unmeasured Anions||Unmeasured Cations|
|Albumin (15 mEq/L)||Calcium (5 mEq/L)|
|Organic acids (5 mEq/L)||Potassium (4.5 mEq/L)|
|Phosphate (2 mEq/L)||Magnesium (1.5 mEq/L)|
|Sulfate (1 mEq/L)|
|Total UA (23 mEq/L)||Total UC (11 mEq/L)|
A metabolic acidosis that results in the accumulation of excess hydrogen ions will cause an increased AG. We will refer to this as an AG metabolic acidosis. This comes about because the excess hydrogen ions bind with free bicarbonate ions to form carbonic acid, driving the carbonic acid buffering equation to the right, resulting in a decreased concentration of bicarbonate:
This reduced bicarbonate concentration results in a reduced measured anion concentration, and in turn a larger AG. Caution is advised in relying too heavily on the AG as a screening measure of acidosis, especially in a clinical context where strong suspicion for organic acidosis exists. While elevated lactic acid levels should bring about a corresponding large AG, multiple studies have shown that the AG fails to predict lactate levels in both critically ill medical and trauma patients.15–17 In the event that an organic acidosis is strongly suspected, measuring blood levels of the organic acid directly (lactate in lactic acidosis, acetate or β-hydroxybutyrate in ketoacidosis) more reliably detects or excludes the underlying disorder.
In contrast, a metabolic acidosis that comes about as a result of a loss of bicarbonate from the extracellular fluid does not result in an increase in the AG. At first, this might seem counterintuitive. When a metabolic acidosis is brought about by bicarbonate loss, however, the kidneys maintain electroneutrality by retaining chloride ions. Since both chloride and bicarbonate are measured anions, the total contribution of measured anion concentration to the AG remains unchanged, although the relative ratio of chloride to bicarbonate will increase. We will refer to this as a non-AG metabolic acidosis, although because of the elevated relative chloride concentration you may see non-AG metabolic acidosis sometimes referred to as hyperchloremic metabolic acidosis.18
Anion Gap Metabolic Acidosis
As mentioned above, an AG metabolic acidosis is brought about by the accumulation of excess hydrogen ions and the subsequent reduction in the bicarbonate concentration by means of the carbonic acid buffering system. Since the extracellular fluid must remain electrically neutral, the reduction in bicarbonate concentration must occur concurrently with an increase in another anion. The unmeasured anion that replaces bicarbonate in maintaining electrical neutrality is the conjugate base to the acid that gave off the excess hydrogen ion. In the case of lactic acidosis, lactic acid gives off its hydrogen ion, leaving behind lactate, a negatively charged ion:
Acids causing an AG metabolic acidosis can be inorganic (sulfate, phosphate), organic (lactate or ketoacids), or exogenous (salicylates). The most common causes of an AG metabolic acidosis can be remembered by the acronym A CAT MUDPILES (see Table 21-7).4,19 A careful history and exam combined with confirmatory tests will help narrow the differential diagnosis.
Table 21-7. A CAT MUDPILES: Common Causes of Anion Gap Metabolic Acidosis and Confirmatory Tests Where Appropriate ||Download (.pdf)
Table 21-7. A CAT MUDPILES: Common Causes of Anion Gap Metabolic Acidosis and Confirmatory Tests Where Appropriate
|Analgesics (NSAID, APAP)||Tylenol level, AST|
|Cyanide, carbon monoxide||CO level, cyanide level|
|Alcoholic ketoacidosis||Serum or urine ketones, ethanol level|
|Methanol, metformin||Osmolal gap|
|Uremia||Serum BUN, creatinine|
|Diabetic ketoacidosis||Serum or urine ketones, blood glucose|
|Iron, isoniazid||Serum iron level, abdominal radiographs|
|Lactic acidosis||Lactate or lactic acid level|
|Ethylene glycol||Osmolal gap|
|Salicylates||Salicylate level, urine ferric chloride|
Nonanion Gap Metabolic Acidosis
Non-AG metabolic acidosis is caused not by the addition or accumulation of an acid, but by the loss, through either renal or gastrointestinal means, of bicarbonate. Causes of non-AG metabolic acidosis are shown in Table 21-8.19
Table 21-8. HARDUP: Common Causes of Nonanion Gap Metabolic Acidosis ||Download (.pdf)
Table 21-8. HARDUP: Common Causes of Nonanion Gap Metabolic Acidosis
- Renal tubular acidosis and renal insufficiency
- Diarrhea and Diuretics
- Pancreatic fistula
The urine AG can be utilized to distinguish between renal and gastrointestinal etiologies for a non-AG metabolic acidosis.5 The urine anion gap (UAG) is calculated by obtaining the spot urine electrolyte values for Na, K, and Cl as follows:
In the event of renal loss of HCO3, the UAG would be large, as bicarbonate is not measured in the UAG and would account for a large amount of the urinary ions. In the event of gastrointestinal loss of bicarbonate, the kidneys would be retaining HCO3, and the UAG would approximate zero.