1. Abstract The interpretation of the acid-base statusis key in medical practice, being its most frequent use in critically ill pregnant patients with any type of hemodynamic alteration such as hemorrhagic shock or septic shock, which happensin most cases, states of hypoperfusion systemic that produce alteration in the acid base state that generates primary disorders such as acidemia or alkalemia and its metabolic or respiratory components. We make an approach through an arterial or venous blood gas analysis, which has the advantage of an evaluation in a short time to be a diagnosis and thus take medical conduct for a better management of the pregnant patient.
Keywords: Acid base disorders; pregnancy; Metabolic acidosis; Metabolic alkalosis; Respiratory acidosis Respiratory alkalosis
2. Introduction For more than 100 years we have been investigating acid-base disorders. The pioneer since 1908 Henderson Hasselbalch, first with a traditional approach, then in 1977 Siggaard and Andersen giving an importance to base excess on the interpretation of blood gases, later in the same year Emmet and Narins on the discovery of Anion Gap, already in 1983 Peter Stewart makes the difference of strong ions, and finally 10 years later in 1993 Gilfix on the method of Stewarthan. All of them have provided fundamentals for the understanding of acid-base balance and discussions still continue on what should be the approach in clinical practice; however, the recommended approach to use is the one that is easiest and most practical for the physician with a simple, easily reproducible approach because the clinical approach to the patient finally ends up having diagnostic, prognostic and therapeutic implications, it is imperative to be precise and fast in the process [1, 2] (Table 1, 2). Citation: Marenco MEL, Management of Acid Base Disorders in Pregnant Woman. Ann Clin Med Case Rep. 2022; V8(13): 1-10 The first step in the evaluation of a basic acid disorder in an obstetric patient is a careful clinical assessment. Several signs and symptoms often provide clues to the underlying acid-base disorder; these include the patient's vital signs (which may indicate shock or sepsis), neurologic status, signs of infection, pulmonary status (respiratory rate and presence or absence of Kussmaul's respiration, cyanosis, and clubbing fingers), and gastrointestinal symptoms (vomiting and diarrhea). Certain underlying medical conditions, such as pregnancy, diabetes, and heart, lung, liver, and kidney disease, may also indicate the cause. The physician should determine if the patient has taken any medications that affect acid-base balance (e.g., laxatives, diuretics, topiramate, or metformin) and should consider signs of intoxication that may be associated with acid-base disturbances (e.g., acetone factor as a sign of diabetic ketoacidosis or isopropyl alcohol intoxication and visual disturbance as a symptom of methanol intoxication). As new interpretation measures emerge for a blood gas measurement it becomes a little more complex, however, with this method there appear to be three interrelationships for solving acid-base problems. The skills can be acquired, learned through schematics or when we are taught, as well as by teachers or computer software. The teacher's expertise cannot be transferred to students in readyto-use templates. The second approach, is the scheme through acid-base curves, also has shortcomings. An acid-base scheme cannot diagnose triple disorders, cannot be used for written exams, and can be lost when you need it most. If an acid-base scheme is used, it should only reinforce conclusions already reached by the same physician [3, 4]. (Algorithm 1; Table 3).
3. Assessment of Primary Acid-Base Disorders and their Secondary Response (Algorithm 1) Empirical observations suggest that the homeostatic response to acid-base disorders is predictable and can be calculated [6, 7]. In response to basic acid metabolic disturbances, changes in respiratory rate develop rapidly and a new steady-state PaCO2 is reached within hours. In cases of persistent respiratory abnormalities, metabolic compensation develops slowly, and 2 to 5 days are required for the plasma bicarbonate concentration to reach a new steady-state level. A respiratory change is termed "acute" or "chronic" depending on whether a secondary change in bicarbonate concentration meets certain criteria. Mixed basic acid disorders are diagnosed when the secondary response differs from that expected [7, 8, 9]. There are several caveats regarding compensatory changes. Blood gas values can always be explained by two or more coexisting basic acid disorders [11]. Experimental studies of severe chronic hypocapnia and hypercapnia in humans are not ethically feasible; therefore, the data are insufficient to construct confidence limits for severe chronic respiratory alkalosis and acidosis. It is generally accepted that compensatory processes can normalize pH only in chronic respiratory alkalosis9. In contrast to older data, data from a more recent study indicate that pH in chronic respiratory acidosis may be normal and in individual cases, higher than generally recognized (pH>7.45) [10, 12, 13]. In addition, the usual compensatory changes in PaCO2 may be limited in cases of severe hypoxemia. The instruments used to measure blood gases and electrolytes may differ, affecting the results [14-15].
4. Assessment of the Metabolic Component of an Acid-Base Disorder Calculating the anion gap is always useful in metabolic derangement32-45. The sum of positive and negative ionic charges in plasma is equal, measurables are: [Na +] + [K +] + [Ca +] + [Mg +] + [H +] + unmeasured cations = [Cl-] + [HCO3] + [CO3] + [OH-] + albumin + phosphate + sulfate + lactate + unmeasured anions (example: inorganic anions) [17,18]. The three ions with the highest plasma concentrations and the largest variations in concentration are used to calculate the excess of "unmeasured anions" in metabolic acidosis that constitutes the "anion imbalance", which is calculated as [Na +] - [ Cl-] - [HCO3- ]. However, a true ionic gap does not exist in vivo, because the sum of the positive and negative ionic charges in plasma must be equal. Wide reference ranges from 3.0 to 12.0 mmol per liter to 8.5 to 15.0 mmol per liter have been reported for the anion gap 19 because of differences in laboratory methods. 18 Consequently, physicians should know the reference range for their own laboratory (algorithm 2).
5. Metabolic Acidosis with High Anion Gap There are many causes of metabolic acidosis with elevated anion imbalance. A useful item for the most common causes is GOLD MARRK (glycol [ethylene and propylene], 5-oxoproline [pyroglutamic acid], l-lactate, d-lactate, methanol, aspirin, renal failure, rhabdomyolysis, and ketoacidosis) [19]. The anion gap increases when bicarbonate concentration decreases relative to sodium and chloride levels due to excessive acid production (e.g., in diabetic ketoacidosis in the pregnant woman, lactic acidosis, and drug- and alcohol-related intoxication), acid underexcretion (in advanced renal failure), cell lysis (in massive rhabdomyolysis), or other circumstances (e.g., use of penicil-linderived antibiotics).
6. Uses and Limitations of Anion Gap Lactic acidosis accountsfor approximately half of the cases of high anion imbalance [19] and is often due to tissue shock or hypoxia [18]. However, anion imbalance is a relatively insensitive reflection of lactic acidosis: approximately half of patients with serum lactate levels between 3.0 and 5.0 mmol per liter have an anion gap within the reference range [39,40]. The anion gap, which has a sensitivity and specificity below 80% for identifying elevated lactate levels, cannot replace a measurement of the serum lactate level [20]. However, lactate levels are not routinely measured or are not always readily available, and a high anion gap may alert. The anion gap is usually not available for an individual patient. Furthermore, it should always be adjusted for albumin concentration because this weak acid can account for up to 75% of the anion gap [20]. Without correction for hypoalbuminemia, the estimated anion gap does not reveal a clinically significant increase in anions (> 5 mmol per liter) in more than 50% of cases. For every 1-g per deciliter decrease in serum albumin concentration, the calculated anion gap should increase by approximately 2.3 to 2.5 mmol per liter [20]. However, the albumin-corrected anion gap is merely an approximation, as it does not consider ions such as magnesium, calcium, and phosphate. Anion gap can help establish the diagnosis of diabetic ketoacidosis. In patients with this condition, the anion gap can be used to track the resolution of ketosis6 and diagnose acidosis with normal anion gap if large volumes of isotonic saline are administered [21]. The pH may also be misleadingly normal or elevated due to concomitant metabolic alkalosis from hyperemesis gravidarum or respiratory alkalosis from fatty liver of pregnancy, high temperature or sepsis [22]. The anion gap can also aid in the diagnosis of lactic acidosis in patients with short bowel syndrome because the standard lactate level remains normal as the anion gap increases [23]. A low or negative anion imbalance is seen when hyperchloremia is caused by high cation levels, as seen in lithium toxicity, monoclonal IgG gammopathy, or disorders characterized by high calcium or magnesium levels. A negative anion gap is caused by pseudo hyperchloremia in bromide or iodide poisoning [24].
The urinary anion gap ([Na +] + [K +] - [Cl-]) is usually negative in acidosis with normal anion gap, but will become positive when urinary ammonium (NH4 +) excretion (as ammonium chloride [NH4Cl]) is altered, such as in kidney injury, distal renal tubular acidosis, or hypoaldosteronism [6]. In normal anion gap acidosis, a negative urinary anion imbalance occurs due to diarrhea and proximal renal tubular acidosis, in which distal acidification is intact. The urinary anion gap becomes unreliable when polyuria is present, when urine pH exceeds 6.5 or when urinary ammonium is excreted with an anion other than chloride (e.g., ketoacids, acetylsalicylic acid, D-lactic acid, and large amounts of penicillin)6. Furthermore, urine acidification requires an adequate distal supply ofsodium; therefore, the usefulness of urinary anion gap is questionable when the urinary sodium level is less than 20 mmol per liter. In such cases, urinary osmolar gap is generally more reliable. The urinary osmolar gap determines the difference between the measured and calculated urinary osmolarity. Urinary osmolarity is calculated as follows: (2 × [Na+] + 2 × [K+]) + (blood urea nitrogen [in milligrams per deciliter] ÷ 2.8) + (glucose [in milligrams per deciliter] ÷ 18) or (in millimoles per liter): (2 × [Na +] + 2 × [K +]) + (blood urea nitrogen) + (glucose) (Table 4).7. Acidosis with Normal Anion Gap Chloride plays a central role in intracellular and extracellular acid-base regulation [25]. A normal anion gap acidosis occurs when the decrease in bicarbonate ions is matched by an increase in chloride ions to retain electroneutrality, also referred to as hyperchloremic metabolic acidosis. This type of acidosis occurs from gastrointestinal loss of bicarbonate (e.g., diarrhea or ureteral shunting), from renal loss of bicarbonate that may occur in defective urinary acidification by the renal tubules (renal tubular acidosis), or in early renal injury when acid excretion is impaired [25, 26]. Hospital-acquired hyperchloremic acidosis is usually caused by infusion of large volumes of "normal" saline (0.9%) [26, 27]. Hyperchloremic acidosis should lead to an increase. Renal ammonium excretion and measurement of urinary ammonium can therefore be used to differentiate between renal and extra renal causes of acidosis with normal anion imbalance. However, since urinary ammonium israrely measured, urinary anion imbalance and urinary osmolar imbalance are often used as surrogate measures of urinary ammonium excretion [6]. The urinary anion gap ([Na +] + [K +] - [Cl-]) is usually negative in acidosis with normal anion gap, but will become positive when urinary ammonium (NH4 +) excretion (as ammonium chloride [NH4Cl]) is altered, such as in kidney injury, distal renal tubular acidosis, or hypoaldosteronism [6]. In normal anion gap acidosis, a negative urinary anion imbalance occurs due to diarrhea and proximal renal tubular acidosis, in which distal acidification is intact. The urinary anion gap becomes unreliable when polyuria is present, when urine pH exceeds 6.5 or when urinary ammonium is excreted with an anion other than chloride (e.g., ketoacids, acetylsalicylic acid, D-lactic acid, and large amounts of penicillin)6. Furthermore, urine acidification requires an adequate distal supply ofsodium; therefore, the usefulness of urinary anion gap is questionable when the urinary sodium level is less than 20 mmol per liter. In such cases, urinary osmolar gap is generally more reliable. The urinary osmolar gap determines the difference between the measured and calculated urinary osmolarity. Urinary osmolarity is calculated as follows: (2 × [Na+] + 2 × [K+]) + (blood urea nitrogen [in milligrams per deciliter] ÷ 2.8) + (glucose [in milligrams per deciliter] ÷ 18) or (in millimoles per liter): (2 × [Na +] + 2 × [K +]) + (blood urea nitrogen) + (glucose) (Table 4).
8. Assessment of the Metabolic Component of an Acid-Base Disorder The diagnosis of metabolic alkalosis is based on the demonstration of a simultaneous increase in blood pH > 7.45 and plasma HCO3 > 26mmol/L in an arterial blood sample. An elevated plasma HCO3 alone should not be considered equal to metabolic alkalosis, as it may also be secondary to compensatory respiratory acidosis. As in any acid-base disorder, evaluation of high blood pH is mandatory to identify the secondary disorder and establish the accurate diagnosis. Once the diagnosis of metabolic alkalosis is made, it is important to evaluate whether respiratory compensation is appropriate (Algorithm 3). En cualquier caso, la alcalosis metabólica tiene un mal pronóstico [31] ya que se asocia a variaciones extremas del pH sanguíneo a pesar de los pequeños cambios en el HCO3 plasmático. La orientación diagnóstica adicional viene dada por el análisis del contenido de electrolitos de una muestra de orina. Un Cloro urinario < 20 mmol/L establece el diagnóstico de cloro sensible alcalosis por depleción, la mayoría de las veces debido a vómitos, succión nasogástrica o la reciente interrupción de diuréticos [32, 33]. Cabe recordar que en los pacientes que padecen diarrea algunos adenomas vellosos secretan cloro y provocan alcalosis metabólica. In the absence of an obvious cause, physical examination may give some suspicion of surreptitious vomiting: such as ulcers and calluses on the back of the hand, dental erosions and swollen cheeks [34, 35]. Urinary Chlorine is also low in post-hypercapnic metabolic alkalosis, the diagnosis of which is usually suggested by the clinical context. A urinary chlorine > 20 mmol/L indicates chloride-resistant alkalosis, always due to increased distal cation exchange [32, 33] and requiring assessment of blood pressure and plasma renina inactivity (Table 5).
9. Key Points for Metabolic Alkalosis [36] 1. Metabolic alkalosis is a common complication in patients with congestive heart failure receiving diuretics. 2. This acid-base disturbance, when severe, can cause adverse effects on cellular function and contribute to increased mortality. 3. Treatment to normalize acid-base abnormalities is indicated. 4. Correction of chloride depletion and normalization of extracellular fluid volume are essential for the correction of metabolic alkalosis. 5. Carbonic anhydrase antagonists such as acetazolamide and aldosterone are useful in correcting metabolic alkalosis in patients with volume overload. 6. In patients with severe metabolic alkalosis, hydrochloric acid or dialysis may be necessary for rapid correction of alkalosis (Table 6).
10. Adverse Clinical Effects of Metabolic Alkalosis that Justify Treatment [37, 38] -Vasoconstriction (gestational hypertensive syndrome, myocardial ischemia, cerebral ischemia) - Eclampsia - Delirium - Arrhythmias (mainly due to associated hypokalemia) - Hypoventilation leading to hypercapnia and hypoxia. - Hypokalemia - Hypocalcemia - Hypomagnesemia - Hypophosphatemia (mainly respiratory alkalosis)
11. Respiratory Alkalosis - Respiratory alkalosis and hypocapnia occur with alveolar hyperventilation resulting from the following: - Stimulation of peripheral chemoreceptors by hypoxemia. - Activation of hypoxemia-independent pulmonary stretch recepTable 7: Causes of Respiratory Alkalosis tors or nonciceptors - Direct activation of central respiratory centers. - Overzealous mechanical ventilation - Fear, excitement, pain, fever, or sepsis. - After treatment of metabolic acidosis since hyperventilation may still be present for 24 to 48 hours after therapy. Clinical signs in patients with respiratory alkalosis are primarily attributes of the underlying disease process and are infrequent due to the efficient metabolic compensation that capable of the underlying disease process and are infrequent because of the efficient metabolic compensation that occurs. Tachypnea may be the only clinical sign, especially in patients who have chronic hypocapnia. In some patients who have acute alkalosis, cardiac arrhythmias, confusion, and eclampsia or posterior reversible encephalopathy syndrome (PRES) may be seen. Alkalosis-induced translocation of potassium into cells with additional renal and extrarenal losses may produce signs attributable to hypokalemia (e.g., neuromuscular weakness, arrhythmias, polyuria) in acute respiratory alkalosis (Table 7-9).
12. Manifestations of Respiratory Acidosis - Neuromuscular anxiety - Asterixis - Lethargy, stupor, coma Delirium - Convulsions (Eclampsia) - Headache - Papilledema - Focal paresis - Tremors, myoclonus - Cardiovascular tachycardia, Vasodilatation Ventricular arrhythmias - Increased serum total carbon dioxide content - Hypochloremia - Acute increase of serum phosphorus (Table 10).
References 1. Story DA. Bench-to-bedside review: A brief history of clinical acid-base. Crit Care. 2004; 8: 253–8.
2. Edwards SL. Pathophysiology of acid base balance:The theory practice relationship. Intensive Crit Care Nurs. 2008; 24: 28–38.
3. Lee C, Rutecki GW, Clarett M, Jarjoura D, Whittier F. A comparison of interactive computerized medical education software with a more traditional teaching format. 1997.
4. Whittier FC, Rutecki GW. The little yellow book. Fluids and electrolytes: a guide to everyday practice. Anadem Publications. 2000.
5. Sterns RH. Fluid, electrolyte and acid-base disturbances: nephrology self-assessment program (Neph SAP). In: Glassock RJ, editor. Philadelphia (PA): Lippincott, Williams & Wilkins and American Society of Nephrology; 2003.
6. Reddy P, Mooradian AD. Clinical utility of anion gap in deciphering acid-base disorders. Int J Clin Pract. 2009; 63: 1516-25.
7. Krapf R, Beeler I, Hertner D, Hulter HN. Chronic respiratory alkalosis the effect of sustained hyperventilation on renal regulation of acid-base equilibrium. N Engl J Med. 1991; 324: 1394-401.
8. Lolekha PH, Vanavanan S, Lolekha S. Update on value of the anion gap in clinical diagnosis and laboratory evaluation. Clin Chim Acta. 2001; 307: 33-6.
9. Martinu T, Menzies D, Dial S. Reevaluation of acid-base prediction rules in patients with chronic respiratory acidosis. Can Respir J. 2003; 10: 311-5.
10. Henderson LJ. The theory of neutrality regulation in the animal organism. Am J Physiol. 1908; 21: 427-48.
11. Finkel KW, Dubose TF. Metabolic acidosis. In: Dubose T Jr, Hamm L, eds. Acid base and electrolyte disorders: a companion to Brenner & Rector’s The Kidney. Philadelphia: Saunders. 2002; 55-66.
12. Jones NL. Respiratory acidosis sans acidemia. Can Respir J. 2003; 10: 301-3.
13. Ucgun I, Oztuna F, Dagli CE, Yildirim H, Bal C. Relationship of metabolic alkalosis, azotemia and morbidity in patients with chronic obstructive pulmonary dis- ease and hypercapnia. Respiration. 2008; 76: 270-4.
14. Otani N, Ohde S, Mochizuki T, Ishimatsu S. Reliability of anion gap calculated from data obtained using a blood gas analyzer: is the probability of error predict- able? Am J Emerg Med. 2010; 28: 577- 81.
15. Sarrazin F, Tessler MJ, Kardash K, McNamara E, Holcroft C. Blood gas measurements using the Bayer Rapid Point 405: are we basing our decisions on ac- curate data? J Clin Monit Comput. 2007; 21: 253-6.
16. Galla JH. Metabolic alkalosis. J Am Soc Nephrol. 2000; 11: 369-75.
17. Feldman M, Soni N, Dickson B. Influ- ence of hypoalbuminemia or hyperalbu- minemia on the serum anion gap. J Lab Clin Med. 2005; 146: 317-20.
18. Gunnerson KJ, Saul M, He S, Kellum JA. Lactate versus non-lactate metabolic acidosis: a retrospective outcome evalua- tion of critically ill patients. Crit Care. 2006; 10: R22.
19. Farwell WR, Taylor EN. Serum anion gap, bicarbonate and biomarkers of in- flammation in healthy individuals in a national survey. CMAJ. 2010; 182: 137-41.
20. Chawla LS, Shih S, Davison D, Junker C, Seneff MG. Anion gap, anion gap cor- rected for albumin, base deficit and un- measured anions in critically ill patients: implications on the assessment of metabolic acidosis and the diagnosis of hyper- lactatemia. BMC Emerg Med. 2008; 8: 18.
21. Noritomi DT, Soriano FG, Kellum JA, et al. Metabolic acidosis in patients with severe sepsis and septic shock: a longitu- dinal quantitative study. Crit Care Med. 2009; 37: 2733-9.
22. Ahya SN, José Soler M, Levitsky J, Batlle D. Acid-base and potassium disorders in liver disease. Semin Nephrol. 2006; 26: 466-70.
23. Chang YM, Chiew YW, Yang CS. The case mid R: a woman with severe meta- bolic acidosis. Kidney Int. 2010; 77: 261-2.
24. Kraut JA, Madias NE. Serum anion gap: its uses and limitations in clinical medicine. Clin J Am Soc Nephrol. 2007; 2: 162-74.
25. Katzir Z, Dinour D, Reznik-Wolf H, Nissenkorn A, Holtzman E. Familial pure proximal renal tubular acidosis a clinical and genetic study. Nephrol Dial Transplant. 2008; 23: 1211-5.
26. Corey HE, Vallo A, Rodríguez-Soriano J. An analysis of renal tubular acidosis by the Stewart method. Pediatr Nephrol. 2006; 21: 206-11.
27. Rodríguez Soriano J. Renal tubular acidosis: the clinical entity. J Am Soc Nephrol. 2002; 13: 2160-70.
28. Rennke HG, Denker BM. Renal pathophysiology, the essentials. 3rd ed. Philadelphia: Lippincott Williams & Wilkins. 2010.
29. Mirza N, Marson AG, Pirmohamed M. Effect of topiramate on acid-base balance: extent, mechanism and effects. Br J Clin Pharmacol. 2009; 68: 655-61.
30. Duewall JL, Fenves AZ, Richey DS, Tran LD, Emmett M. 5-Oxoproline (pyroglutamic) acidosis associated with chronic acetaminophen use. Proc (Bayl Univ Med Cent). 2010; 23: 19-20.
31. Anderson K, Henrich WL. Alkalemia-associated morbidity and mortality in medical and surgical patients. South Med J. 1987; 880: 729-33.
32. Palmer BF, Alpern RJ. Metabolic alkalosis. J Am Soc Nephrol. 1997; 8: 1462-9.
33. Galla JH. Metabolic alkalosis. J Am Soc Nephrol. 2000; 11:369-75.
34. House RC, Grisius R, Bliziotes MM, Licht JH. Perimolysis: un veiling the surreptitious vomiter. Oral Surg Oral Med Oral Pathol. 1981; 51: 152-5.
35. Richardson RM, Forbath N, Karanicolas S. Hypokalemic metabolic alkalosis caused by surreptitious vomiting: report of fourcases. Can Med Assoc J. 1983; 129: 142-5.
36. Peixoto AJ, Alpern RJ. Treatment of severe metabolic alkalosis in a patient with congestive heart failureAm J Kidney Dis. 2013;61(5):822-827.
37. Adrogue HJ, Madias NE. Management of life-threatening acid-base disorders. Second of two parts. N Engl J Med. 1998; 338(2): 107- 111.
38. Galla JH. Metabolic alkalosis. In: DuBose TG, Hamm LL, eds. Acid-Base and Electrolyte Disorders. Philadelphia, PA: Saun- ders. 2002: 109-128.
39. Palmer BF. Evaluation and treatment of respiratory alkalosis. Am J Kidney Dis. 2012;60(5):834-838
40. N engl j med 371;15 nejm.org october 9, 2014
41. Medical Clinics of North America-1983; l(67): 4.
42. Nag K, Singh DR, Shetti AN, Kumar H, Sivashanmugam T, Parthasarathy S. Sugammadex: A revolutionary drug in neuromuscular pharmacology. Anesthesia: Essays and Researches; 2013; 7(3): 3026.
Mario Enmanuel López Marenco. Management of Acid Base Disorders in Pregnant Woman . Annals of Clinical and Medical Case Reports 2022