Maternal–Fetal Blood Gas Physiology 59 quantitative assessment of the expected compensatory changes (Table 5.1 ). A systematic approach to an acid – base abnormality Several different approaches for blood gas interpretation have been devised [53 – 55] . A six - step approach modifi ed from Narins and Emmitt provides a simple and reliable method to analyze a blood gas, particularly when a complicated mixed disorder is present [33,56,57] . This method, adjusted for pregnancy, is as follows (Figure 5.3 ). 1 Is the patient acidemic or alkalemic? If the arterial blood pH is < 7.36, the patient is acidemic, while a pH > 7.44 defi nes alkalemia. 2 Is the primary disturbance respiratory or metabolic? The primary alteration associated with each of the four primary disorders is shown in Table 5.1 . 3 If a respiratory disturbance is present, is it acute or chronic? The equations listed in Table 5.1 are used to determine the acuteness of the disturbance. The expected change in the pH is calculated and the measured pH is compared to the pH that would be expected based on the patient ’ s PCO 2 . 4 If a metabolic acidosis is present, is the anion gap increased? Metabolic acidosis is classifi ed according to the presence or absence of an anion gap. methods of acid – base interpretation have been devised, including graphic nomograms and step - by - step analysis. Each method is detailed in this section to aid in rapid and correct diagnosis of disturbances in acid – base balance. Blood gas results are not a substitute for clinical evaluation of a patient, and laboratory values do not necessarily correlate with the degree of clinical compromise. A typical example is the patient with an acute exacerbation of asthma who experiences severe dyspnea and respiratory compromise before developing hyper- capnea and hypoxemia. Thus, a blood gas is an adjunct to clinical judgment, and decision - making should not be based on a single test. Graphic nomogram Nomograms are a graphic display of an equation and have been designed to facilitate identifi cation of simple acid – base distur- bances [49 – 52] . Figure 5.2 is an example of a nomogram with arterial blood pH represented on the x - axis, HCO 3 − concentration on the y - axis, and arterial PCO 2 on the regression lines. Nomograms are accurate for simple acid – base disturbances, and a single disorder can be identifi ed by plotting measured blood gas values. When blood gas values fall between labelled areas, a mixed disorder is present and the nomogram does not apply. These complex disorders must then be characterized by 100 90 80 70 60 50 40 30 20 60 56 52 48 44 40 36 32 28 24 20 16 12 8 4 0 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 CHRONIC RESPIRATORY ACIDOSIS METABOLIC ALKALOSIS ACUTE RESPIRATORY ACIDOSIS NORMAL ACUTE RESPIRATORY ALKALOSIS CHRONIC RESP. ALKALOSIS METABOLIC ACIDOSIS P CO 2 (mmHg) 10 15 20 25 30 35 405060708090100120 110 Arterial blood pH Arterial plasma [HCO 3 ] (mmol/L) – Figure 5.2 Nomogram for interpretation of simple acid – base disorders. (Reproduced by permission from Cogan MJ. In: Brenner BM, Rector FC Jr, eds. The Kidney. Philadelphia: WB Saunders, 1986: 473.) Chapter 5 60 by a change in maternal position [3] . Abnormal gas exchange, inadequate ventilation or both can lead to a fall in P a O 2 . Hypoxemia is defi ned as a P a O 2 below 60 mmHg or a saturation less than 90%. At this level, the oxygen content of blood is near its maximum for a given hemoglobin concentration and any additional increase in arterial oxygen tension will increase oxygen content only a small amount. The amount of oxygen combined with hemoglobin is related to the P a O 2 by the oxyhemoglobin dissociation curve and infl u- enced by a variety of factors (Figure 5.4 ). The shape of the oxy- hemoglobin dissociation curve allows P a O 2 to decrease faster than oxygen saturation until the P a O 2 is approximately 60 mmHg. A left shift of the curve increases hemoglobin ’ s affi nity for oxygen and oxygen content, but decreases release of O 2 in peripheral tissues. The fetal or neonatal oxyhemoglobin dissociation curve is shifted to the left as a result of fetal hemoglobin and lower levels of 2,3 - DPG. (Figure 5.4 ) The increased affi nity of hemo- globin for oxygen allows the fetus to extract maximal oxygen from maternal blood. A shift to the right has the opposite effect, with decreased oxygen affi nity and content but increased release in the periphery. 5 If a metabolic disturbance is present, is the respiratory compensation adequate? The expected PCO 2 for a given degree of metabolic acidosis can be predicted by Winter ’ s formula (Table 5.1 ), since the relationship between PCO 2 and HCO 3 − is linear. Predicting respiratory compensation for metabolic alkalosis, however, is not nearly as consistent as with acidosis. 6 If the patient has an anion gap metabolic acidosis, are additional metabolic disturbances present? The excess anion gap represents bicarbonate concentration before the anion gap acidosis devel- oped. By calculating the excess gap, an otherwise undetected non - anion gap acidosis or metabolic alkalosis may be detected. Respiratory components of the arterial blood gas Partial pressure of arterial oxygen: P a O 2 The P a O 2 refl ects the lung ’ s ability to provide adequate arterial oxygen. Normal arterial oxygen tension during pregnancy ranges from 87 to 106 mmHg, depending upon the altitude at which a patient lives. Although P a O 2 has been reported to decrease by 25% when samples are obtained from gravidas in the supine position [11] , arterial blood gas values have been shown to be unaffected pH <7.36 >7.44 Metabolic acidosis (HCO 3 – < 20) Metabolic alkalosis (HCO 3 – > 20) Respiratory acidosis (PCO 2 > 30) Respiratory alkalosis (PCO 2 < 30) Measure: Determine: Calculate: Calculate: Serum Na + ,Cl - ,CO 2 Anion gap = Na + – (Cl - + HCO 3 - ) Is respiratory compensation adequate? Is it acute or chronic? Expected pH See Table 5.1 < 20 < 24 > 20 > 24 Excess anion gap = Measured bicarb + (anion gap –12) Coexisting primary metabolic acidosis Coexisting nongap metabolic acidosis Figure 5.3 A systematic approach to the interpretation of an arterial blood gas during pregnancy. Maternal–Fetal Blood Gas Physiology 61 ratio is 500 – 600 and correlates with a shunt of 3 – 5% while a shunt of 20% or more is present when the ratio is less than 200. Calculation of the alveolar – arterial oxygen gradient is also an oxygen tension calculation. The A – a gradient is most reliable when breathing room air and is normally less than 20. An increased gradient indicates pulmonary dysfunction. A – a gradi- ent values, however, can change unpredictably with changes in F i O 2 and vary with alterations in oxygen saturation and con- sumption. Thus, the utility of this measurement in critically ill patients has been questioned since these patients often require a high F i O 2 and have unstable oxygenation [61] . Additionally, the A – a gradient appears to be unreliable in the assessment of lung impairment during pregnancy [11] . Oxygen content - based indices include the shunt equation and estimated shunt as derived from the shunt equation (Table 5.3 ). The estimated shunt has been shown to be superior to the oxygen tension - based indices described above [58] . The patient is given 100% oxygen for at least 20 minutes before determining arterial and venous blood gases and hemoglobin. Since the estimated shunt equation does not require a pulmonary artery blood sample, the C (a – v) O 2 difference is assumed to be 3.5 mL/dL. A normal shunt in non - pregnant patients is less than 10%, while a 20 – 29% shunt may be life - threatening in a patient with compro- mised cardiovascular or neurologic function, and a shunt of 30% and greater usually requires signifi cant cardiopulmonary support. Intrapulmonary shunt values during normal pregnancy, however, have been reported to be nearly three times above the mean for non - pregnant individuals [12] . The mean Qs/Qt in normotensive primiparous women at 36 – 38 weeks gestation ranges from 10% in the knee – chest position to 13% in the stand- ing position and 15% in the lateral position. The increased Qs/ Qt can be explained by the physiologic changes of pregnancy as follows. Lung volumes decrease during gestation and the amount of shunt increases. In addition, pulmonary blood fl ow increases secondary to increased cardiac output. The combined effect of decreased lung volumes and increased pulmonary fl ow results in a higher intrapulmonary shunt during pregnancy. Oxygenation of peripheral tissues An adequate P a O 2 is only the initial step in oxygen transport, however, and it does not guarantee well - oxygenated tissues. The degree of intrapulmonary shunt, oxygen delivery, and oxygen consumption all contribute to adequate tissue oxygenation. Accurate assessment of peripheral oxygenation requires measure- ment of arterial and venous partial pressures of oxygen, arterial and venous oxygen saturation, hemoglobin, and cardiac output (Table 5.3 ). The amount of O 2 (mL) contained in 100 mL of blood defi nes oxygen content. Oxygen delivery (DO 2 ) is the volume of O 2 brought to peripheral tissues in 1 minute and consumption (VO 2 ) is the volume used by the tissues in 1 minute. Under normal conditions, delivery of oxygen is 3 – 4 times greater than consumption. Oxygen extraction measures the amount of O 2 transferred to tissues from 100 mL of blood and can be thought Assessment of lung function Impairment of lung function can be estimated using an oxygen tension - or oxygen content - based index. Oxygen tension - based indices include: (i) expected P a O 2 for a given fraction of inspired oxygen (F i O 2 ); (ii) P a O 2 /F i O 2 ratio; and (iii) alveolar – arterial oxygen gradient (P (A – a) O 2 ). These methods are quick and easy to use but have limitations in the critically ill patient [58] . The shunt calculation (Qsp/Qt) is an oxygen content - based index and is the most reliable method of determining the extent to which pulmo- nary disease is contributing to arterial hypoxemia. The need for a pulmonary artery blood sample is a disadvantage, however, as not all patients require invasive monitoring. The estimated shunt calculation (est. Qsp/Qt) is derived from the shunt equation and is the optimal method to estimate lung compromise when a pul- monary artery catheter is not in place. The expected P a O 2 is an oxygen tension - based calculation and can be quickly estimated by multiplying the actual percentage of inspired oxygen by 6 [59] . Thus, a patient receiving 50% oxygen has an expected PO 2 of (50 × 6) or 300 mmHg. Alternatively, the F i O 2 (e.g. 0.50 in a patient receiving 50% oxygen) may be multi- plied by 500 to estimate the minimum PO 2 [60] . The P a O 2 /F i O 2 ratio has been used to estimate the amount of shunt. The normal 100 90 80 70 60 50 40 30 20 10 0 0 Left shift Alkalosis 2,3-DPG P CO 2 Hypothermia Carbon monoxide Fetal hemoglobin Right shift Acidosis 2,3-DPG PCO 2 Hyperthermia 10 Adult 20 HbO 2 saturation (%) 30 40 50 60 70 80 90 100 P O 2 mmHg (pH 7.40) Neonatal (a–v)O 2 Figure 5.4 Maternal and fetal oxyhemoglobin dissociation curves. 2,3 - DPG, 2,3 - diphosphoglycerate. (Reproduced by permission from Semin Perinatol. WB Saunders, 1984; 8:168.) Chapter 5 62 can no longer provide adequate excretion of CO 2 . Clinically, this is recognized as tachypnea, tachycardia, intercostal muscle retraction, accessory muscle use, diaphoresis and paradoxical breathing. The metabolic component of the arterial blood gas: bicarbonate Measurement of bicarbonate refl ects a patient ’ s acid – base status. The bicarbonate concentration reported with a blood gas is cal- culated using the Henderson – Hasselbalch equation and repre- sents a single ionic species. Total serum CO 2 (tCO 2 ) content is measured with serum electrolytes and is the sum of the various forms of CO 2 in serum. Bicarbonate is the major contributor to tCO 2 , and additional forms include dissolved CO 2 , carbamates, carbonate, and carbonic acid. The calculated bicarbonate con- centration does not include carbonic acid, carbonate, and carbamates. Frequently, arterial and venous blood samples are obtained simultaneously, making arterial blood gas bicarbonate and venous serum tCO 2 measurements available. Venous serum tCO 2 content is 2.5 – 3 mEq/L higher than arterial blood gas bicarbon- ate, since CO 2 content is higher in venous than arterial blood and all species of carbon dioxide are included in the determination of tCO 2 . If the blood sample is arterial, the tCO 2 content reported on the electrolyte panel should be 1.5 – 2 mEq/L higher than the calculated bicarbonate. The tCO 2 measured directly with serum electrolytes will be higher because it includes the different forms of CO 2 . Since both blood gas bicarbonate and electrolyte tCO 2 determinations are usually available, there is a split of opinion as to the relative clinical utility of each [63] . A recent review, however, concludes that calculated and measured bicarbonate values are close enough in most cases that either is acceptable for clinical use [64] . Disorders of acid – base balance Metabolic acidosis Metabolic acidosis is diagnosed on the basis of a decreased serum bicarbonate and arterial pH. The baseline bicarbonate concentra- tion during pregnancy should, of course, be kept in mind when interpreting bicarbonate concentration. Metabolic acidosis develops when fi xed acids accumulate or bicarbonate is lost. Accumulation of fi xed acid occurs with overproduction as in diabetic ketoacidosis or lactic acidosis, or with decreased acid excretion as in renal failure. Diarrhea, a small bowel fi stula, and renal tubular acidosis can all result in loss of extracellular bicarbonate. Although the clinical signs associated with metabolic acidosis are not specifi c, multiple organ systems may be affected. Tachycardia develops with the initial fall in pH, but bradycardia usually predominates as the pH drops below 7.10. Acidosis causes venous constriction and impairs cardiac contractility, increasing venous return while cardiac output decreases. Arteriolar dilation of as CaO 2 – CvO 2 . Thus, an O 2 extraction of 3 – 4 mL/dL suggests adequate cardiac reserve to supply additional oxygen if demand increases. Inadequate cardiac reserve is indicated by an O 2 extrac- tion of 5 mL/dL or greater, and tissue extraction must be increased to meet changing metabolic needs [62] . Mixed venous oxygen tension (P v O 2 ) and saturation (S v O 2 ) are measured from pulmonary artery blood. These measurements are better indicators of tissue oxygenation than arterial values since venous blood refl ects peripheral tissue extraction. Normal arterial oxygen saturation is 100% and venous saturation is 75%, yielding a normal arteriovenous difference (S a O 2 – S v O 2 ) of 25%. An increased S v O 2 ( > 80%) can occur when oxygen delivery increases, oxygen consumption decreases, (or some combination of the two), cardiac output increases, or the pulmonary artery catheter tip is in a pulmonary capillary instead of the artery. A decrease in S v O 2 ( < 50 – 60%) may be due to increased oxygen consumption, decreased cardiac output or compromised pulmonary function. The venous oxygen saturation may not change at all, however, even with signifi cant cardiovascular changes. Partial pressure of arterial carbon dioxide: P a CO 2 The metabolic rate determines the amount of carbon dioxide that enters the blood. Carbon dioxide is then transported to the lung as dissolved CO 2 , bicarbonate, and carbamates. It diffuses from blood into alveoli and is removed from the body by ventilation, or the movement of gas into and out of the pulmonary system. Measurement of the arterial partial pressure of carbon dioxide allows assessment of alveolar ventilation in relation to the meta- bolic rate. Ventilation (V E ) is the amount of gas exhaled in 1 minute and is the sum of alveolar and dead space ventilation (V E = V A + V DS ). Alveolar ventilation (V A ) is that portion of the lung that removes CO 2 and transfers O 2 to the blood, while dead space (V DS ) has no respiratory function. As dead space increases, ventilation must increase to maintain adequate alveolar ventilation. Dead space increases with a high ventilation – perfusion ratio (V/Q) (i.e. an acute decrease in cardiac output, acute pulmonary embolism, acute pulmonary hypertension, or ARDS) and positive - pressure ventilation. Since P a CO 2 refl ects the balance between production and alve- olar excretion of carbon dioxide, accumulation of CO 2 indicates failure of the respiratory system to excrete the products of metab- olism. The primary disease process may be respiratory or a process outside the lungs. Extrapulmonary processes that increase metabolism and CO 2 production include fever, shivering, sei- zures, sepsis, and physiologic stress. Parenteral nutrition with glucose providing more than 50% of non - protein calories can also contribute to high CO 2 production. Recognizing respiratory acid – base imbalance is important because of the need to assist in CO 2 elimination. As V E increases, the work of breathing can cause fatigue and respiratory failure. It is important to recognize that the P a CO 2 may initially be normal, but rises as the work of breathing exceeds a patient ’ s functional reserve. Ventilatory failure occurs when the pulmonary system Maternal–Fetal Blood Gas Physiology 63 sured ions. Na + and K + account for 95% of cations while HCO 3 − and Cl − represent 85% of anions [66] . Thus, unmeasured anions are greater than unmeasured cations. The anion gap is the differ- ence between measured plasma cations (Na + ) minus measured anions (Cl − , H CO 3 − ) and is derived: Total anions Total cations unmeasured anions = += Measured anions mmeasured cations Cl tCO 2 + [] + [] + unmeasured cations unmeasured aanions unmeasured cations Unmeasured anions unme ⎛ ⎝ ) = [] + ⎛ ⎝ ) − Na ++ aasured cations = [] − [] + [] () = [] − [] Na Cl tCO 2 ++ ++ Anion gap Na Cl + ttCO 2 [] () A normal anion gap is 8 – 16 mEq/L. Potassium may be included as a measured cation, although it contributes little to the accuracy or utility of the gap. If K + is included in the calculation, however, the normal range becomes 12 – 20 mEq/L [67] . A change in the gap involves a change in unmeasured cations or anions. An elevated gap is most commonly due to an accumu- lation of unmeasured anions that include organic acids (i.e. keto- acids or lactic acid), or inorganic acids (i.e. sulfate and phosphate) [68] . A decrease in cations (i.e. magnesium and calcium) will also increase the gap, but the serum level is usually life - threatening. occurs at pH < 7.20. Respiratory rate and tidal volume increase in an attempt to compensate for the acidosis. Maternal acidosis can result in fetal acidosis as H + ions equilibrate across the placenta, and fetal pH is generally 0.1 pH units less than the maternal pH. The compensatory response to metabolic acidosis is an increase in ventilation that is stimulated by the fall in the pH. Hyperventilation lowers PCO 2 as the body attempts to return the HCO PCO 32 − [] ratio toward normal. The respiratory response is proportional to the degree of acidosis and allows calculation of the expected PCO 2 for a given bicarbonate level (Table 5.1 ). When the measured PCO 2 is higher or lower than expected for the measured serum bicarbonate, a mixed acid – base disorder must be present. This formula is ideally applied once the patient has reached a steady state, when PCO 2 nadirs 12 – 24 hours after the onset of acidosis [56] . The classifi cation of metabolic acidosis as non - anion gap or anion gap acidosis helps determine the pathologic process. Once a metabolic acidosis is detected, serum electrolytes should be obtained to calculate the anion gap. Frequently the clinical history and a few additional diagnostic studies can identify the underly- ing abnormality (Figure 5.5 ) [65] . Electroneutrality in the body is maintained because the sum of all anions equals the sum of all cations. Na + , K + , Cl − , and HCO 3 − are the routinely measured serum ions while Mg + , Ca 2+ , proteins (particularly albumin), lactate, HPO 4 − and SO 4 − are the unmea- pH, HCO 3 2– Calculate anion gap Elevated anion gap Measure: Serum glucose Serum ketones Serum creatinine Lactate Serum osmolality Toxin screen Salicylate level Ethylene glycol ingestion Lactic acidosis Methanol ingestion Paraldehyde ingestion Propylene glycol ingestion Salicylate toxicity Renal failure (late acute or early chronic) Ketoacidosis Diabetic Alcoholic Starvation Normal anion gap Gastrointestinal bicarbonate loss Diarrhea Small bowel fistula Renal tubular acidosis Medication Carbonic anhydrase inhibitors (e.g., acetozolamide) Amphotericin B Cyclosporine Cholestyramine Acid ingestion Hypoaldosteronism Renal failure (early acute or mild chronic) Figure 5.5 Etiology and evaluation of metabolic acidosis. Chapter 5 64 The following example demonstrates use of the anion gap in a patient who had been experiencing dysuria, polyuria, and poly- dypsia of several days duration. Initial evaluation of this 19 - year - old gravida at 24 weeks gestation was notable for a serum glucose level of 460 mg/dL and 4+ urinary ketones. Further investigation revealed: arterial pH of 7.30, HCO 3 − of 14 mEq/L, serum Na + of 133 mEq/L, K + of 4.1 mEq/L, tCO 2 of 15 mEq/L, and Cl − of 95 mEq/L. The anion gap was determined: Anion gap Na Cl tCO mEq L mEq L mEq L = [] − [] + [] () =−+ () = +− − 2 133 95 15 13 33 110 23 mEq L mEq L Anion gap mEq L − = The elevated anion gap is the result of unmeasured organic anions or ketoacids that have accumulated and decreased serum bicarbonate. As this patient with type I diabetes mellitus receives insulin therapy, the anion gap will normalize, refl ecting disap- pearance of the ketoacids from the serum. The limitations of the anion gap, however, should be recog- nized. Various factors can lower the anion gap, but its importance is not so much in the etiology of the decrease as in its ability to mask an elevated gap. Since albumin accounts for the majority of unmeasured anions, the gap decreases as albumin levels fall. For each 1 g decrease in albumin, the gap may be lowered by 2.5 – 3 mEq/L. The most common cause of a lowered gap is decreased serum albumin. Other less common causes include markedly elevated levels of unmeasured cations (K + , Mg + , and Ca 2+ ), hyper- lipidemia, lithium carbonate intoxication, multiple myeloma, and bromide or iodide intoxication. Although an elevated anion gap is traditionally associated with metabolic acidosis, it may also occur in the presence of severe metabolic alkalosis. The ionic activity of albumin changes with increasing pH and protons are released. The net negative charge on each molecule increases, thereby increasing unmeasured anions. Volume contraction leads to hyperproteinemia and aug- ments the anion gap. If an anion gap acidosis is present, the ratio of the change in the anion gap (the delta gap) to the change in HCO 3 − can be helpful in determining the type of disturbances present: ∆ ∆ gap HCO Anion gap HCO 33 12 24 −− = − − [] In simple anion gap metabolic acidosis, the ratio approximates 1.0, since the decrease in bicarbonate equals the increase in anions. The delta gap for the patient with diabetes and ketoaci- dosis previously described is calculated as follows: ∆ ∆ gap HCO Anion gap HCO 33 12 24 23 12 24 14 11 10 11 −− = − − [] = − − ==. The delta gap is 0 when the acidosis is a pure non - anion gap acidosis. A delta gap of 0.3 – 0.7 is associated with one of two mixed metabolic disorders: (i) a high anion gap acidosis and respiratory alkalosis and (ii) high anion gap with a pre - existing normal or low anion gap. A ratio greater than 1.2 implies a meta- bolic alkalosis superimposed on a high anion gap acidosis or a mixed high anion gap acidosis and chronic respiratory acidosis. The use of the delta gap is, however, limited by the wide range of normal values for the anion gap and bicarbonate, and its accuracy has been questioned [69] . When a normal anion gap metabolic acidosis is present, the urinary anion gap may be helpful in distinguishing the cause of the acidosis: urinary anion gap urine Na urine K urine Cl= [] + [] − [] ++ − The urinary anion gap is a clinically useful method to estimate urinary ammonium ( NH 4 + ) excretion. Since the amount of NH 4 + excreted in the urine cannot be directly measured, the urinary anion gap helps determine whether the kidney is responding appropriately to a metabolic acidosis [70] . Normally, the urine anion gap is positive or close to zero. A negative gap (Cl − > N a + and K + ) occurs with gastrointestinal bicarbonate loss and NH 4 + excretion by the kidney increases appropriately. In contrast, a positive gap (Cl − < N a + and K + ) in a patient with acidosis suggests impaired distal urinary acidifi cation with inappropriately low NH 4 + excretion. A variety of processes can lead to metabolic acidosis and therapy will depend on the underlying condition. Adequate oxy- genation should be ensured and mechanical ventilation instituted for impending respiratory failure. The use of bicarbonate solu- tions to correct acidosis has been suggested when arterial pH is less than 7.10 or bicarbonate is lower than 5 mEq/L. Bicarbonate solutions must be administered with caution since an “ over- shoot ” alkalosis can lower seizure threshold, impair oxygen avail- ability to peripheral tissues, and stimulate additional lactate production. Metabolic alkalosis Metabolic alkalosis is characterized by a rise in serum bicarbonate concentration and an elevated arterial pH. The most impressive clinical effects of metabolic alkalosis are neurologic and include confusion, obtundation, and tetany. Cardiac arrhythmias, hypo- tension, hypoventilation and various metabolic aberrations may accompany these neurologic changes. Metabolic alkalosis results from a loss of acid or the addition of alkali. The development of metabolic alkalosis occurs in two phases, with the initial addition or generation of HCO 3 − followed by the inability of the kidney to excrete the excess HCO 3 − . The two most common causes of metabolic alkalosis are excessive loss of gastric secretions and diuretic administration. Once established, volume contraction, hypercapnea, hypokalemia, glucose loading, and acute hypercalcemia promote HCO 3 − reabsorption by the kidney and sustain the alkalosis. Maternal–Fetal Blood Gas Physiology 65 a responsive disorder, infusion of sodium chloride will correct the abnormality. Conversely, saline administration will not correct a chloride resistant disorder and can be harmful. Treatment of the primary disease will concurrently correct the alkalosis. Although mild alkalemia is generally well tolerated, critically ill surgical patients with a pH ≥ 7.55 have increased mortality [72,73] . Respiratory acidosis Respiratory acidosis is characterized by hypercapnea (a rise in PCO 2 ) and a decreased arterial pH. The development of respira- tory acidosis indicates the failure of carbon dioxide excretion to match CO 2 production. A variety of disorders can contribute to this acid – base abnormality (Table 5.4 ). It is important to remem- ber that the normal PCO 2 in pregnancy is 30 mmHg, and norma- tive data for non - pregnant patients do not apply to the gravida. The clinical manifestations of acute respiratory acidosis are particularly evident in the central nervous system. Since carbon dioxide readily penetrates the blood – brain barrier and cerebro- spinal fl uid buffering capacity is not as great as blood, PCO 2 elevations quickly decrease the pH of the brain. Thus, neurologic compromise may be more signifi cant with respiratory acidosis than metabolic acidosis [59] . Acute hypercapnia also decreases The degree of respiratory compensation for metabolic alkalosis is more variable than with metabolic acidosis, and formulas to estimate the expected P a CO 2 have not proven useful [56] . Alkalosis tends to cause hypoventilation but P a CO 2 rarely exceeds 55 mmHg [56,71] . Tissue and red blood cells attempt to lower HCO 3 − by exchanging intracellular H + ions for extracellular Na + and K + . Once metabolic alkalosis is diagnosed, determination of urinary chloride concentration can be helpful in determining the etiology (Figure 5.6 ). Urinary chloride is a more reliable indicator of volume status than urinary sodium concentration in this group of patients. Sodium is excreted in the urine with bicarbonate to maintain electroneutrality and occurs independently of volume status. Therefore, low urinary chloride in patients with volume contraction accurately refl ects sodium chloride retention by the kidney. A urinary chloride concentration < 10 mEq/L that improves with sodium chloride administration is a chloride - responsive metabolic alkalosis. In contrast, a urine chloride > 20 mEq/L indi- cates that the alkalosis will not improve with saline administra- tion and is a chloride - resistant alkalosis. Urine chloride levels must be interpreted with caution since levels are falsely elevated when obtained within several hours of diuretic administration. Treatment of metabolic alkalosis is aimed at eliminating excess bicarbonate and reversing factors responsible for main- taining the alkalosis. If the urinary chloride level indicates pH, HCO 3 – Measure urinary chloride Chloride resistant (Urine Cl – > 20 mEq/L) Hypertensive: Mineralocorticoid excess Hyperaldosteronism Normotensive: Magnesium depletion Diuretic use (current) Profound hypokalemia Alkali ingestion Bicarbonate therapy Antacids Lactate Acetate Citrate Massive blood transfusion Hypercalcemia Medications Carbenicillin Penicillin Sulfates Parathyroid disease Refeeding alkalosis Chloride responsive (Urine Cl – < 10 mEq/L) Gastrointestinal Vomiting Nasogastric suction Diuretic use (discontinued) Contraction alkalosis Posthypercapnea Figure 5.6 Etiology and evaluation of metabolic alkalosis. Table 5.4 Causes of respiratory acidosis. Airway obstruction Aspiration Laryngospasm Severe bronchospasm Impaired ventilation Pneumothorax Hemothorax Severe pneumonia Pulmonary edema Adult respiratory distress syndrome Circulatory collapse Massive pulmonary embolism Cardiac arrest CNS depression Medication Sedatives Narcotics Cerebral infarct, trauma or encephalopathy Obesity – hypoventilation syndrome Neuromuscular disease Myasthenic crisis Severe hypokalemia Guillain – Barr é Medication Chapter 5 66 acid – base disorder in which the compensatory response can return the pH to normal. Respiratory alkalosis may be diagnostic of an underlying con- dition and is usually corrected with treatment of the primary problem. Hypocapnea itself is not life - threatening but the disease causing the alkalosis may be. The presence of respiratory alkalosis should always raise suspicion for hypoxemia, pulmonary embo- lism, or sepsis. These conditions, however, can be overlooked if the only concern is correction of the alkalosis. Mechanical venti- lation may lead to iatrogenic respiratory alkalosis and the PCO 2 can usually be corrected by lowering the machine - set respiratory rate. [75] References 1 Kruse JA . Acid – base interpretations . Crit Care 1993 ; 14 : 275 . 2 MacRae DJ , Palavradji. Maternal acid – base changes in pregnancy . J Obstet Gynaecol Br Cwlth 1967 ; 74 : 11 . 3 Hankins GDV , Harvey CJ , Clark SL , Uckan EM . The effects of mater- nal position and cardiac output on intrapulmonary shunt in normal third - trimester pregnancy . Obstet Gynecol 1996 ; 88 : 327 . 4 Cruikshank DP , Hays PM . Maternal physiology in pregnancy . In: Gabbe S , Niebyl J , Simpson JL , eds. Obstetrics: Normal and Problem Pregnancies , 2nd edn. New York : Churchill Livingstone , 1991 : 129 . cerebral vascular resistance, leading to increased cerebral blood fl ow and intracranial pressure. The compensatory response depends on the duration of the respiratory acidosis. In acute respiratory acidosis, the respiratory center is stimulated to increase ventilation. Carbon dioxide is neutralized in erythrocytes by hemoglobin and other buffers, and bicarbonate is generated. An acute disturbance implies that renal compensation is not yet complete. Sustained respiratory acidosis (longer than 6 – 12 hours) stimulates the kidney to increase acid excretion, but this mechanism usually requires 3 – 5 days for full compensation [74] . The primary goal in the management of respiratory acidosis is to improve alveolar ventilation and decrease arterial PCO 2 . Assessment and support of pulmonary function are paramount when a patient has respiratory acidosis. Carbon dioxide accumu- lates rapidly, and PCO 2 rises 2 – 3 mmHg/min in a patient with apnea. The underlying condition should be rapidly corrected and may include relief of an airway obstruction or pneumothorax, administration of bronchodilator therapy, narcotic reversal, or a diuretic. Adequate oxygenation is crucial because hypoxemia is more life - threatening than hypercapnia. In the pregnant patient, hypoxemia also compromises the fetus. Uterine perfusion should be optimized and maternal oxygenation ensured since the com- bination of maternal hypoxemia and uterine artery hypoperfu- sion profoundly affects the fetus. When a patient cannot maintain adequate ventilation despite aggressive support, endotracheal intubation and mechanical ventilation should be performed without delay. Respiratory alkalosis Respiratory alkalosis is characterized by hypocapnea (decreased PCO 2 ) and an increased arterial pH. Acute hypocapnea frequently is accompanied by striking clinical symptoms, including pares- thesias, circumoral numbness, and confusion. Tachycardia, chest tightness, and decreased cerebral blood fl ow are some of the prominent cardiovascular effects. Chronic respiratory alkalosis, however, is usually asymptomatic. Respiratory alkalosis is the result of increased alveolar ventila- tion (Table 5.5 ). Hyperventilation can develop from stimulation of brainstem or peripheral chemoreceptors and nociceptive lung receptors. Higher brain centers can override chemoreceptors and occurs with involuntary hyperventilation. Respiratory alkalosis is commonly encountered in critically ill patients in response to hypoxemia or acidosis, or secondary to central nervous system dysfunction. The compensatory response is divided into acute and chronic phases. In acute alkalosis, there is an instantaneous decrease in H + ion concentration due to tissue and red blood cell buffer release of H + ions. If the duration of hypocapnea is greater than a few hours, renal excretion of bicarbonate is increased and acid excretion is decreased. This response requires at least several days to reach a steady state. Chronic respiratory alkalosis is the only Table 5.5 Causes of respiratory alkalosis. Pulmonary disease Pneumonia Pulmonary embolism Pulmonary congestion Asthma Drugs Salicylates Xanthines Nicotine CNS disorders Voluntary hyperventilation Anxiety Neurologic disease Infection Trauma Cerebrovascular accident Tumor Other causes Pregnancy Pain Sepsis Hepatic failure Iatrogenic mechanical hyperventilation Maternal–Fetal Blood Gas Physiology 67 28 Bloom SA , Canzanello VJ , Strom JA , Madias NE . Spurious assessment of acid – base status due to dilutional effect of heparin . Am J Med 1985 ; 79 : 528 . 29 New W . Pulse oximetry . J Clin Monit 1985 ; 1 : 126 . 30 Al - Ameri MW , Kruse JA , Carlson RW . Blood sampling from arterial catheters: minimum discard volume to achieve accurate laboratory results . Crit Care Med 1986 ; 14 : 399 . 31 Bhaskaran NC , Lawler PG . How much blood for a blood gas? Anesthesiology 1988 ; 43 : 811 . 32 Biswas CK , Ramos JM , Agroyannis B , Kerr DNS . Blood gas analysis: effect of air bubbles in syringe and delay in estimation . 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