There is a surprising degree of fluctuation in blood gas values in normal persons and in stabilized sick persons. In one study of normal persons using arterialized capillary blood, changes of at least 10% in bicarbonate or total CO2, 15% in PCO2, and 170% in base excess were required to exceed normal day-to-day variation. In another study, this time using arterial samples from stabilized ICU patients, average fluctuations within patients without known cause were found of 3.0 mm Hg (range 1-8 mm Hg) for PCO2, 0.03 pH units (range 0.01-0.08 units) for pH, and 16 mm Hg (range 1-45 mm Hg) for PO2. There were sufficient variation in repeat samples drawn at 10 minutes and at about 1 hour that a change of about 10% at 10 minutes and of about 20% at 1 hour was necessary to be considered significant. This suggests caution in making decisions based on small changes in acid-base or PO2 values.
Category: Acid-Base and pH Measurements
Acid-Base and pH Measurements
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Newborn and Neonatal Blood Gas Measurement
A number of studies have found that umbilical cord arterial pH is the best available indicator of fetal acidosis, which would suggest intrauterine fetal hypoxia. Arterial pH was found to be more accurate than arterial PCO2, PO2, cord venous pH, or Apgar score. Although there is some disagreement regarding cord arterial pH reference range, a pH of 0.15 appears to be the best cutoff point (I obtained the same value in a group of 122 consecutive newborns).
There is also data from several studies of heelstick (or other capillary site) puncture specimens for blood gas PO2, PCO2, or pH measurement versus arterial specimens. The studies generally found adequate correlations in healthy term infants, less correlation in premature newborns, and increasingly poor correlation of all parameters as severity of illness increased, especially in premature newborns. The conclusion was that capillary blood gas results must be interpreted with much caution in severely ill newborns or neonates.
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Noninvasive Measurement of PCO2, PO2, and Oxygen Saturation
There are now several ways to measure carbon dioxide and oxygen in blood without drawing a blood sample. The two most popular methods at present are transcutaneous electrode systems and pulse oximetry. Both systems can provide continuous readings.
The transcutaneous systems use PCO2 and PO2 electrodes similar to those of standard arterial blood gas analysis applied directly to the skin over a gel sealant. Skin has capillaries close to the surface, and the tissues are permeable to some extent for carbon dioxide and oxygen. The apparatus heats the skin to 44°C to produce arterialized blood, thereby dilating the capillaries and increasing oxygen loss. The electrode sensors detect the carbon dioxide and oxygen diffusing from the capillaries. The apparatus must be moved at least every 4-6 hours in adults and 2-4 hours in infants to prevent thermal burns. The apparatus must be calibrated with a standard arterial blood gas sample obtained by arterial puncture each time the apparatus is positioned due to variability from differences in fat content (which interferes with gas diffusion) and skin thickness. Patient edema, hypothermia, or poor tissue perfusion (shock or vasoconstriction) interfere to varying degrees with accurate measurements.
Pulse oximetry measures hemoglobin oxygen saturation (percentage of hemoglobin structurally capable of binding oxygen that is saturated with oxygen) rather than oxygen tension (PO2). The method uses two light beams, one red and the other infrared, which are passed through tissue that contains arterial blood. Opposite to the light emitters are light detectors. The light detectors perform two tasks. First, they recognize and analyze arterial blood exclusively by differentiating those areas that have pulsation, and therefore changes in light transmission, from nonvascular tissue and nonarterial vascular components. Then oxygen saturation is measured in the pulsating vessels using the fact that changes in oxygen content have a significant effect on absorption of red light. The amount of red light absorption (transmission) is compared to that of the infrared light, which is affected much less. This system does not have to be calibrated by arterial puncture blood and does not have to be moved frequently. The instrument is accurate between saturation levels of about 70%-100%. When PO2 is above 100 mm Hg, hemoglobin is usually 100% saturated, reaching the upper limit of the oximeter. Below 70% saturation, accuracy becomes less, but trends in saturation change can be recognized. Carboxyhemoglobin can interfere with measurement. Since the instrument measures only oxygenation, acid-base abnormalities must be detected or investigated by some other method.
Abnormal results from either transcutaneous monitors or pulse oximeters must be confirmed by arterial puncture blood gas measurement. The pulse oximeter is usually attached to a toe in infants, to a finger in adults, and to the nose in obese adults.
Noninvasive continuous oxygen monitors are especially useful during anesthesia since most serious problems involve episodes of hypoxia; in premature or sick neonates and infants; in patients on ventilators; and in intensive care unit (ICU) patients or other unstable seriously ill adults.
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Blood Lactate
Under conditions of adequate or near-adequate tissue oxygenation, glucose is metabolized for energy production using the aerobic metabolic pathway that converts glucose metabolic products to pyruvate that is, in turn, metabolized in the citric acid (Krebs) cycle. Under conditions of severe tissue hypoxia, aerobic metabolism cannot function properly, and glucose metabolic products at the pyruvate state stage are converted to lactate (lactic acid) by anaerobic metabolism. Therefore, increase in blood lactate is one indication of significantly decreased tissue oxygenation. Compared to other indicators of abnormal oxygen availability, PO2 decrease is best at suggesting decreased pulmonary alveolar uptake of oxygen, oxygen saturation methods demonstrate arterial oxygen content, and blood lactate shows the metabolic consequence of tissue hypoxia. In general, blood lactate is a fairly sensitive and reliable measurement of tissue hypoxia. It can be used to diagnose clinically important tissue hypoxia, to determine (roughly) the degree of hypoxia, to estimate tissue oxygen debt (the size of the accumulated oxygen deficit accumulated during a period of hypoxia), and to monitor the effect of therapy. Lactate can be increased in local ischemia if severe or extensive enough (e.g., grand mal seizures, or severe exercise; mesenteric artery insufficiency) as well as generalized ischemia (cardiac decompensation, shock, or carbon monoxide poisoning). The majority of patients exhibiting relatively large increases in blood lactate have metabolic acidosis, either primary or mixed (with respiratory acidosis or alkalosis).
Lactic acidosis has been divided into two groups: tissue hypoxia (discussed above) and conditions not involving significant tissue hypoxia. In the latter group are included severe liver disease (decreased metabolism of lactate), malignancy, drug-induced conditions (e.g., from cyanide, ethanol, and methanol), and certain inborn errors of metabolism. Idiopathic lactic acidosis associated with diabetes appears to combine a minor element of tissue hypoxia with some unknown triggering factor. In general, etiologies not primarily associated with tissue hypoxia tend to have lesser degrees of blood lactate elevation and better survival (with the exception of idiopathic lactic acidosis). However, there is a very significant degree of overlap in survival between the two classification groups. Another problem is controversy over definition of lactic acidosis. One frequently accepted definition is a lactate reference range of 0.5-1.5 mEq/L (mmol/L), hyperlactatemia when blood lactate persists in the 2.0-5.0 mEq/L range, and lactic acidosis when blood lactate exceeds 5 mEq/L (mmol/L) accompanied by metabolic acidosis. RBC metabolism increases lactate, so that specimens need special preservatives plus immediate ice cooling with early separation of the plasma, or else a bedside whole-blood analyzer.
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Blood Oxygen Studies
The greatest stimulus for arterial as opposed to venous specimens for blood gas studies is to obtain measurement of blood oxygen. The usual information reported is PO2 (concentration of O2 gas measured in mm of Hg or Torr), obtained with a direct-reading PO2 electrode. PO2 represents the dissolved oxygen content of plasma, analogous to the relationship of PCO2 to CO2. Reference ranges for PO2 are age related. In persons under age 60 (breathing room air), 80-95 mm Hg is considered normal. Over age 60, 1 mm Hg per year, but no more than 20 mm Hg, is subtracted from the lower limit of the reference range. A PO2 of 60-80 mm Hg is classified as mild hypoxemia, a PO2 of 40-60 mm Hg represents moderate hypoxemia, and a PO2 less than 40 mm Hg represents severe hypoxemia.
Blood oxygen studies are done for three reasons. First, they help indicate the current status of alveolar gas exchange with inspired air. PO2 provides this information. A normal PO2 while breathing room air indicates adequate pulmonary ventilation.
The second reason is to determine the amount of oxygen available to body cells. PO2 is less adequate for this purpose, because most of the oxygen in the blood is not dissolved oxygen but oxygen bound to RBC hemoglobin. The measurement one really needs is oxygen saturation, which is the actual amount of oxygen bound to hemoglobin compared with the theoretical amount that should be bound to the same amount of hemoglobin (or, the amount of hemoglobin bound to oxygen compared to the amount of hemoglobin available for binding). Then, the quantity of hemoglobin times percent saturation times the factor 1.34 gives the total quantity of oxygen in the blood (except for the very small amount of dissolved oxygen). When the hemoglobin level is normal and PO2 is normal, the percent saturation and total oxygen content are usually adequate. In fact, many blood gas machines provide a calculated oxygen saturation value derived from PO2, normal hemoglobin levels, and data from the normal oxgyen-hemoglobin dissociation curve. Although there is adequate correlation between calculated oxygen saturation and actual (true) oxygen saturation (measured in a special instrument such as a CO-Oximeter) at normal hemoglobin and PO2 values, calculated O2 saturation results can become significantly incorrect at subnormal PO2 values, due to the sigmoid (S) shape of the oxygen-hemoglobin dissociation curve. In the steep midportion of the S curve, a relatively small decrease in PO2 leads to a relatively large decrease in oxygen saturation. In addition, there are a considerable number of conditions that shift the curve to greater or lesser degree and affect oxygen saturation. Nevertheless, a decreased PO2 suggests the possibility of tissue hypoxia, and the degree of PO2 decrease provides a rough estimate of the probability and severity of tissue hypoxia. Certain conditions decrease blood oxygen content or tissue oxygen independently of PO2. These include anemia (producing decreased hemoglobin and therefore decreased oxygen-carrying capacity), carbon monoxide poisoning (CO replaces O2 on the hemoglobin molecule), acidosis (which increases oxygen dissociation from hemoglobin), and congestive heart failure (which slows blood flow and decreases tissue perfusion rate). Hemoglobins that do not carry oxygen (e.g., Hb F), if present in sufficient quantity, result in decreased O2 saturation values.
The third reason for PO2 measurement is to monitor effects of oxygen therapy. The usual goal is to raise PO2 above the lower limit of the reference range. However, in some patients, oxygen therapy may be adequate but unable to provide a normal PO2.
Oxygen saturation (SaO2) is another frequently used parameter of tissue oxygenation. This is a measurement of arterial blood oxygen content. As discussed previously, SaO2 can be measured directly by an instrument called a CO-oximeter or estimated by calculation from PO2 and hemoglobin quantity; it can also be measured indirectly by means of a pulse oximeter (discussed later).
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Anion Gap
Once metabolic acidosis is apparent, the problem becomes one of identifying the cause. Calculation of the anion gap may be helpful. The anion gap is the difference between the major cations (sodium, or sodium plus potassium) and the major anions (chloride and bicarbonate). The anion gap formula is: AG = Na – (C1 + HCO–3). If the anion gap is increased, and especially when it is more than 10 mEq/L above the upper limit of the reference range, excess organic acids or acidic foreign substances should be suspected. Conditions in which these may appear include diabetic ketoacidosis, ethyl alcohol-induced ketoacidosis, renal failure, lactic acidosis, salicylate overdose, and methanol or ethylene glycol poisoning. The value most often listed for normal anion gap is 8-16 mEq/L (mmol/L). However, there is some disagreement in the literature whether to use a range of 8-12 or 8-16 mEq/L for a normal anion gap. Some investigators use the sum of sodium plus potassium in the equation rather than sodium alone. Although one would expect this to decrease the normal anion gap, the reference values reported in the literature are the same or even greater than those for the formula using sodium alone, with some listing a range of 8-16 mEq/L and others 8-20 (values in the literature can be found extending from 7-25 mEq/L). Anion gap reference ranges established on hospitalized patients tend to be higher than those established on outpatients. A collection tube filled to less than one third of tube capacity can result in a falsely decreased bicarbonate and falsely increased anion gap.
A decreased anion gap has been associated with multiple myeloma. However, one report indicates that most calculated anion gaps that are decreased result from laboratory error in test results included in the equation, with hypoalbuminemia and hyponatremia the next most common associated findings.
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Other Comments on Acid-Base Problems
The preceding discussion applies to an acid-base problem involving a single primary metabolic or primary respiratory abnormality, with or without body attempts at compensation. Unfortunately, in some cases the laboratory picture is more complicated; for example, when there are superimposed attempts at therapy or when two different acid-base processes coexist (referred to as “mixed acid-base disorders”). An example is diabetic acidosis (metabolic acidosis) in a patient with chronic lung disease (compensated respiratory acidosis). In this circumstance it is very important to decide what serious clinical condition the patient has (e.g., renal failure, diabetic acidosis, chronic lung disease) that might affect the acid-base status and then what other conditions may be superimposed (such as vomiting, diuretic therapy, or shock) that could alter the acid-base picture in a certain direction.
PCO2 Values in Metabolic and Respiratory Acid-Base Disorders
PCO2 NORMAL
An abnormality in pH means an uncompensated metabolic process.
PCO2 ABNORMAL
PCO2 decreased
Could be respiratory (hyperventilation) in origin (respiratory alkalosis). If so, pH should be increased (acute onset), or normal, but more than 7.40 (chronic-compensated).
Could be metabolic acidosis. If so, pH should be decreased (partial compensation), or normal but more than 7.40 (fully compensated).
PCO2 increased:
Could be respiratory (hypoventilation) in origin (respiratory acidosis). If so, pH should be decreased (acute onset), or normal but less than 7.40 (chronic-compensated).
Could be metabolic alkalosis. If so, pH should be increased (partial compensation), or normal, but more than 7.40 (fully compensated).In some cases of acid-base disturbance, such as classic diabetic acidosis, the diagnosis may be obvious. In other cases the diagnosis is made from the first set of arterial blood gas measurements. In these two situations, continued acid-base studies are needed only to gauge the severity of the disorder and response to therapy. If the PO2 does not indicate respiratory impairment, it may be sufficient to obtain PCO2 or HCO3 values, with or without pH determination, on venous specimens rather than make repeated arterial punctures.
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Interpretation of Acid-Base Data
Acid-base data interpretation has always been one of the more difficult areas of laboratory medicine. In most uncomplicated untreated cases the diagnosis can be achieved with reasonable ease. There are several ways of approaching an acid-base problem. One way is to examine first the arterial PCO2 value. Since primary respiratory disorders result from hypoventilation or hyperventilation, which, in turn, are reflected by a change in arterial PCO2, normal PCO2 with abnormal pH is strong evidence against a primary respiratory disorder and should be an uncompensated metabolic disorder.
If PCO2 is decreased, there are two major possibilities:
1. The primary disorder could be respiratory alkalosis (hyperventilation). If so, pH should be increased in acute (uncompensated) cases or partially compensated cases. In fully compensated cases pH is within reference range, but frequently it is more than 7.40 even within the reference range.
2. The primary disorder could be metabolic acidosis. If so, pH should be decreased in partially compensated cases. In fully compensated cases pH is within its reference range (similar to fully compensated respiratory alkalosis), but frequently it is less than 7.40 even within the reference range.
If PCO2 is increased, there are also two major possibilities:
1. The primary disorder could be respiratory acidosis (hypoventilation). If so, pH should be decreased in acute (uncompensated) cases or partially compensated cases. In fully compensated cases pH is within reference range, but frequently it is less than 7.40 even within reference range.
2. The primary disorder could be metabolic alkalosis. If so, pH should be increased in partially compensated cases. In fully compensated cases pH is within its reference range (similar to fully compensated respiratory acidosis), but pH frequently is more than 7.40 even within the reference range.
There is another way to interpret the data. If one first inspects pH, decreased pH means acidosis and increased pH means alkalosis. One then inspects the PCO2 value. If the PCO2 has changed in the same direction as the pH, the primary disorder is metabolic. If the PCO2 has changed in the opposite direction from that of the pH, the primary disorder is respiratory.
Base excess analysis is not a vital part of this type of algorithm. However, base excess can sometimes be helpful, both as additional evidence for certain types of acid-base disorders or to help detect the presence of active acid-base disorder in fully compensated cases. A negative base excess is found in metabolic acidosis and, to a lesser extent, in respiratory alkalosis. A positive base excess is found in metabolic alkalosis and, to a lesser extent, in respiratory acidosis.
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Buffer Base and Base Excess
The concepts of buffer base and base excess form part of the Astrup acid-base system. The term buffer base refers to all substances in the buffering system of whole blood that are able to bind excess H+. Bicarbonate forms slightly more than one half of the total buffer base; hemoglobin makes up about one third of the total buffer base, consisting of three fourths of the nonbicarbonate buffer system. Normal buffer base values for any patient are therefore calculated on the basis of the actual hemoglobin concentration as well as normal values for pH and HCO–3. The term base excess refers to any difference in the measured total quantity of blood buffer base from the patient’s calculated normal value. Thus, an increase in total buffer base (e.g., an increase in HCO–3) is considered a positive base excess; a decrease in total buffer base from calculated normal (e.g., a decrease in HCO–3) is considered a negative base excess (some prefer to use the terms “base excess” and “base deficit” rather than positive or negative base excess). Venous blood has a base excess value about 2.0-2.5 mEq/L higher than arterial blood.
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Acid-Base Compensation
Compensation refers to the degree of PCO2 change when there is, or has been, an abnormality in pH.
An uncompensated disorder is a primary metabolic or respiratory condition that has not been altered by any significant degree of correction. In the case of a primary metabolic condition the respiratory counterbalance (change in ventilation which is reflected by a change in arterial PCO2) is not evident; pH is abnormal but PCO2 remains normal. In the case of a primary respiratory condition, both PCO2 and pH are abnormal, and the degree of abnormality on both tests is relatively severe. In that case the renal counterbalance (increased bicarbonate formation to bring pH back toward normal) is not evident.
A partially compensated disorder is present when both pH and PCO2 are outside their reference ranges. In primary respiratory disorders, the degree of pH abnormality is not as severe as in uncompensated cases.
A fully compensated (sometimes referred to only as compensated) condition is a primary metabolic or respiratory disorder in which PCO2 is outside its reference range but pH has returned to its reference range.