• Metabolic acidosis is usually accompanied by respiratory compensation (tachypnea).
• Chronic respiratory acidosis is usually accompanied by gradual metabolic compensation (increases in serum bicarbonate).
• Acute respiratory acidosis is usually not accompanied by immediate metabolic compensation.
• The most common cause of a non–anion-gap metabolic acidosis is bicarbonate loss from diarrhea.
The human body tightly regulates its acid–base environment, keeping the serum pH close to 7.40 (normal values = 7.35-7.45). As pH is a negative logarithmic scale this corresponds to a concentration of H+in serum of 0.00004 mEq/L1—which is dramatically less than the concentration of sodium (135–145 mEq/L) and other ions. Significant shifts away from the normal pH result in cellular alterations that lead to changes to systemic and pulmonary vascular resistance, reduced cardiac output and sensitivity to inotropes, precipitate arrhythmias and can put the patient at risk of death.1 Carbonic acid (H2CO3) and its buffering salt bicarbonate play key roles in the metabolic component of pH.
When the usual hemostatic mechanisms ultimately become overwhelmed with the production of acid or base, acidosis or alkalosis develops. The nearly immediate compensatory response of the body to this change in pH occurs through chemoreceptors in the brain resulting in increases in minute ventilation, lowering the pCO2 in response to a metabolic acidosis (trying to maintain a more normal pH). The renal system is also activated to help correct the acidosis/alkalosis but this process is slower and may take hours to days. The body does not overcompensate such that changes occurring in pCO2 through changes in ventilation or metabolic changes via the kidneys will only bring the pH toward neutral but will not convert an acidosis to alkalosis or vice versa.2
INTERPRETING A BLOOD GAS
The states of having an abnormally low or high pH are referred to as acidemia and alkalemia, respectively. The term compensation refers to the homeostatic mechanism the body uses to generate a compensatory acidosis or alkalosis, as an attempt to normalize pH, when faced with a pathologic acid–base disturbance.2
The pH, the pCO2 and the pO2 are measured, while the bicarbonate level and base excess/deficit are calculated estimations. A serum bicarbonate measurement in the chemistry laboratory is an actual measurement, rather than a calculation but in most instances, the calculated and measured values should be very close to each other. Recent literature in adult trauma victims suggests the base deficit may be very useful in predicting transfusion requirements and risk of mortality, and may better identify shock severity than current Advanced Trauma Life Support (ATLS) classification based on clinical signs.3,4
The gold standard for blood gas measurement remains an arterial specimen but this often proves difficult to obtain, is unnecessarily invasive for most children and carries a small risk of complications.5Venous or capillary specimens are generally easier to obtain and there is good correlation for pH, pCO2, base excess and bicarbonate.6 An arterial specimen should be obtained when pO2 or co-oximetry measurement is required (e.g., when the pulse oximeter has a poor perfusion signal due to severe shock, or when it is unreliable as in a patient with carbon monoxide poisoning or methemoglobinemia).7
The first step in analyzing the blood gas is to look at the pH. A value less than 7.4 reflects an acidosis and regardless of what other processes may be simultaneously occurring, the primary process is an acidosis. Similarly, a pH value of greater than 7.4 reflects a primary alkalosis with a primary process of an alkalosis. The next step should be look at the pCO2 and bicarbonate. In the context of an acidosis, an elevated pCO2 suggests the primary process is a respiratory acidosis and a low bicarbonate suggests a metabolic acidosis (the combination of both suggests mixed respiratory and metabolic acidosis). Conversely, in an alkalemic presentation, a low pCO2 indicates respiratory alkalosis and a high bicarbonate indicates a metabolic alkalosis.
The next step should determine if the compensation is appropriate. If not, there may be multiple acid–base disturbances occurring simultaneously. In acute respiratory acidosis, an increase of 10 mm Hg usually decreases the pH by 0.08, and a compensatory bicarbonate increase of 1 mEq/L as an attempt to normalize the pH. For chronic changes in pCO2 the kidney is better able to compensate and the bicarbonate will increase by 3.5 mEq/L for the same 10 mm Hg increase in pCO2.8 This difference in compensation may help the clinician determine the chronicity of the patient’s symptoms when it is not readily apparent on history. As an example, a 5-month old former 26-week premature infant with chronic lung disease presenting with a pCO2 of 60 mm Hg and a bicarbonate 31 mEq/L likely has chronic CO2retention compared to an infant with a pCO2 of 60 mm Hg and a bicarbonate of 26 mEq/L who has an acute process that will require more aggressive therapy.
In the context of a metabolic acidosis, every 1 mEq/L decrease in serum bicarbonate should result in a compensatory 1.2 mm Hg drop in the patient’s pCO2.9 There are limits to this compensation and it is uncommon to see patients with a pCO2 below 10 mm Hg.1,9
Metabolic acidosis is commonly noted on blood gases of ill children presenting to the ED. A practical method to think about the underlying cause of the acidosis is to calculate the anion gap and determine if the patient has an anion-gap positive or anion-gap negative metabolic acidosis. Recognizing that the net charge of blood is neutral, the total number of positively charged cations (Na+, K+, Ca++, etc.) must match the total number of negatively charged anions (Cl-, HCO3-, etc.). Sodium and potassium make up about 95% of the cations. Chloride and bicarbonate make up 85% of the anions. The remaining 5% of the cations and 15% of anions can simplistically be referred to as the “unmeasured” cations and anions, respectively. The anion gap reflects the difference in the plasma concentrations of the “measured” cations and anions but can be conceptualized as reflecting the difference in “unmeasured” cations and anions (must be an equal amount to maintain electrical neutrality). Some experts define the anion gap as:
An anion gap of up to approximately 12 mEq/L is considered normal when using the first equation and an anion gap of up to approximately 16 mEq/L is acceptable when using the latter. There is little difference between the two equations when accounting for the acceptable norms and physicians should use the formula with which they have greater comfort or is recommended at their institution.
A non–anion-gap metabolic acidosis generally results from the loss of bicarbonate with an associated physiologic response to increase serum chloride to maintain the total measured anions unchanged (and therefore there is no change in the anion gap). Examples of non–anion-gap metabolic acidosis include the loss of bicarbonate in diarrhea or through the kidneys from renal tubular acidosis (RTA). The RTA is generally type I, II, or IV but may also result from a medication-induced RTA type pathophysiology. The history, particularly the presence or absence of diarrhea and medications that may induce RTA, generally point to the correct diagnosis. In rare instances, the primary problem precipitating a non–anion-gap metabolic acidosis may be an excess of chloride that could result following a large volume of resuscitation with normal saline (0.9% NaCl).
Anion-gap metabolic acidosis is caused by etiologies in the mnemonic MUDPILES (methanol, uremia, diabetic ketoacidosis, paraldehyde/propylene glycol, iron/isoniazid/inborn errors of metabolism, lactic acidosis, ethylene glycol, salicylates), the most common of which is lactic acidosis due to poor tissue perfusion, which can usually be reversed by giving fluids to improve perfusion. Albumin contributes significantly to the “unmeasured” anions and when serum albumin is low (e.g., nephrotic syndrome, malnutrition, hepatic failure), the normal range for the anion gap should be adjusted.10 Giving bicarbonate is generally not indicated for most patients and may be harmful to some patients such as those in diabetic ketoacidosis.11 Sodium bicarbonate does have a role treating patients with salicylate overdose, to alkalinize urine and enhance salicylate elimination, and to increase blood pH in the context of a tricyclic antidepressant overdose with widening of the QRS complex.
Clinical assessment of dehydration in children with gastroenteritis is imperfect.12 When laboratory studies are used, a bicarbonate level of greater than 15–17 mEq/L suggests that significant dehydration is not present.12 Patients with diarrhea often have bicarbonate loss and the degree of dehydration is sometimes exaggerated by the bicarbonate level. For example, a patient with a bicarbonate of 13 mEq/L but with no increase in anion gap has no significant amount of lactic acid generation (due to euvolemia and normal perfusion), yet the bicarbonate is very low as a consequence of bicarbonate loss alone.
Metabolic alkalosis results from an excessive loss of H+ ions from the body, such as with vomiting or nasogastric suctioning, or a net gain of HCO3-. Hyperaldosteronism or other mineralocorticoid excess can result in sodium reabsorption in the kidneys with secretion of H+ and potassium ions similarly resulting in a metabolic alkalosis. Use of a loop diuretic inhibits the reabsorption of sodium and chloride at the ascending loop of Henle resulting in extracellular fluid volume reduction and a contraction alkalosis as the remaining HCO3- is relatively increased in concentration. Rather than excreting the excess HCO3- as one might anticipate, the kidneys respond to the hypovolemia, and metabolic alkalosis is maintained through the renin-angiotensin-aldosterone system. A direct increase in HCO3- may occur for a number of reasons such as milk-alkali syndrome and the use of acetate in parental nutrition.
Metabolic alkalosis is often classified as chloride responsive, where it can be corrected by chloride replacement, or chloride resistant where the alkalosis is caused by hormonal mechanisms (e.g., hyperaldosteronism) that cause ongoing acid and chloride losses. The chloride-responsive forms typically present with hypochloremia, hypokalemia, and extravascular volume contraction. Hyperaldosteronism is present in these situations but it is a secondary, rather than a primary, process. The urine chloride is typically less than 10 mEq/L in a chloride-responsive metabolic alkalosis, though this may not be the case when diuretics are used. The chloride resistant forms typically present with euvolemia or hypervolemia, may have associated hypertension depending on the cause, and will have a urine chloride greater than 20 mEq/L.1
Treatment of chloride-responsive metabolic alkalosis requires replacement of the chloride through infusion of normal saline. If diuretics are the underlying etiology, they may need to be discontinued or weaned. Carbonic anhydrase inhibitors such as acetazolamide may be useful in some cases to lower serum bicarbonate levels. The treatment of chloride resistant metabolic alkalosis generally focuses on treating the mineralocorticoid excess.1
Respiratory acidosis usually presents secondary to impaired CO2 clearance but can, in theory, arise from increased CO2 production. There are numerous specific causes that are beyond the scope of this chapter but they generally revolve around intrinsic lung disease, poor muscle strength (e.g., myasthenia gravis), inhibition of the central respiratory drive or disorders of the chest wall.1 The clinical impact of the respiratory acidosis depends largely on the acuity of the event and the degree of hypoxia. Children tolerate elevated pCO2 fairly well, but hypoxia requires immediate correction.
Treatment of a respiratory acidosis with sodium bicarbonate is inappropriate and potentially harmful,1 yet this classic dogma is being questioned.13
Respiratory alkalosis is a relatively common process that occurs with hyperventilation. In the ED, the most common causes include fear, pain, agitation, and anxiety. More worrisome causes include hypoxemia and all patients with a respiratory alkalosis should be evaluated for respiratory distress and hypoxemia. Mild-to-moderate wheezing in asthma, usually results in a respiratory alkalosis. Other potential causes for respiratory alkalosis include neurologic problems such as raised intracranial pressure, infection or tumor, or medications that might stimulate the respiratory centers in the brain.
The acid–base environment of the body efficiently operates within a narrow range, keeping the serum pH close to 7.40 (normal values = 7.35–7.45). Significant shifts away from the normal pH lead to cellular alterations that cause changes in bodily functions.
When the usual mechanisms are overwhelmed with the production of acid or base, acidosis or alkalosis develops. The body attempts to normalize the pH through compensatory mechanisms of the pulmonary and renal systems.
1. Fortenberry JD, Hebbar K, Wheeler D. Acid-base disorders in the pediatric intensive care unit. In: Wheeler DS, Wong HS, Shanley TP, eds. Pediatric Critical Care Medicine: Basic Science and Clinical Evidence. London: Springer-Verlag; 2007:1176–1188.
2. Carmody JB, Norwood VF. A clinical approach to pediatric acid-base disorders. Postgrad Med J. 2012;88(1037):143–151.
3. Privette AR, Dicker RA. Recognition of hypovolemic shock: using base deficit to think outside of the ATLS box. Crit Care. 2013;17(2):124.
4. Mutschler M, Nienaber U, Brockamp T, et al; the Trauma Register DGU. Renaissance of base deficit for the initial assessment of trauma patients: a base deficit-based classification for hypovolemic shock developed on data from 16,305 patients derived from the Trauma Register DGU. Crit Care. 2013;17(2):R42.
5. McGillivray D, Ducharme FM, Charron Y, Mattimoe C, Treherne S. Clinical decision-making based on venous versus capillary blood gas values in the well-perfused child. Ann Emerg Med. 1999;34(1):58–63.
6. Yildizdaş D, Yapicioğlu H, Yilmaz HL, Sertdemir Y. Correlation of simultaneously obtained capillary, venous, and arterial blood gases of patients in a pediatric intensive care unit. Arch Dis Child.2004;89(2):176–180.
7. Blanc PD. In: Olsen KR. Poisoning and Drug Overdose. New York, NY: McGraw Hill; 2004:261–263.
8. Martinu T, Menzies D, Dial S. Re-evaluation of acid-base prediction rules in patients with chronic respiratory acidosis. Can Respir J. 2003;10:311e15.
9. Herd AM. An approach to complex acid-base problems: keeping it simple. Can Fam Physician. 2005;51:226–232.
10. Feldman M, Soni N, Dickson B. Influence of hypoalbuminemia or hyperalbuminemia on the serum anion gap. J Lab Clin Med. 2005;146(6):317–320.
11. Chua HR, Schneider A, Bellomo R. Bicarbonate in diabetic ketoacidosis - a systematic review. Ann Intensive Care. 2011;1:23.
12. Steiner MJ, DeWalt DA, Byerley JS. Is this child dehydrated? JAMA. 2004;291(22):2746–2754.
13. Buysse CM, de Jongste JC, de Hoog M. Life-threatening asthma in children: treatment with sodium bicarbonate reduces pCO2. Chest. 2005;127(3):866–870.