Clinical approach to the diagnosis of acid-base disorders - NCBI

Clinical approach to the diagnosis of acid-base disorders ROBERT A. BEAR,* MD, FRCP[C], FACP; ROLAND F. DYCK,t MD, FRCP[C]

An ability to rapidly and effectively diagnose and treat acid-base disorders is essential to the management of seriously ill patients. In this paper an approach to the diagnosis of pure and mixed acid-base disorders is presented that is based upon an understanding of the bicarbonate buffer system and a knowledge of the well defined and predictable compensatory responses that occur in association with each of the primary acid-base disorders. With this approach a number of acid-base problems are presented and solved.

of the physiologic adaptations that sibility to determine not only its can be expected to occur in any par- cause but also its specific nature: Is ticular acid-base disorder. In this it acute or chronic, pure or mixed? paper, an update and extension of On occasion, this may be a chalan initial review,1 we present a sim- lenging task indeed. plified approach to acid-base probConsider, for example, a patient lems based upon an understanding of admitted to an intensive care unit these adaptations. Although acid- with chronic obstructive lung disease base "nomograms" exist that are and respiratory failure complicated helpful in evaluating complex acid- by heart failure and fluid retention. base disorders,1 in our view the clin- If the latter problem were managed ical approach detailed below is of with administration of potent saligreater general use to practitioners uretics, "chloride-responsive" metaUne habilet6 A diagnostiquer et A because acid-base nomograms are bolic alkalosis might easily be supertraiter rapidement et effectivement often not readily available for bed- imposed upon pre-existing chronic les d6sequilibres acide-base est essentielle dans le traitement des side use, and because reliance upon respiratory acidosis. Furthermore, patients gravement malades. Dans cette nomograms deprives the clinician of should pneumonia subsequently decommunication on presente un abord the opportunity to achieve a mean- velop, acute respiratory acidosis unau diagnostic des d6s6quilibres acide-base purs et mixtes qui s'appuient ingful, highly useful understanding doubtedly would be added to these of acid-base physiology. other problems. Such a patient's sur Ia comprehension du systeme In a healthy individual the extraoverall acid-base status could not be tampon bicarbonate et sur une connaissance des r6actions compencellular fluid pH - pH being an in- determined simply by measuring the satoires bien definies et previsibles verse and logarithmic expression of extracellular fluid pH, which would qui surviennent en association avec hydrogen ion concentration, or [Hi merely indicate which imbalance was chacun des desequilibres acide-base is generally maintained between predominant. In fact, if the various primaires. Un certain nombre de 7.38 and 7.42. Any depression of pH countervailing disturbances happened problemes acide-base sont presentes et resolus de cette faqon. below 7.38 (i.e., a rise in [He]) to be quantitatively equal the pH constitutes acidemia, and any eleva- would be normal. Fortunately, toManagement of the acutely ill pa- tion above 7.42 (i.e., a decline in day's clinician, using clinical skills tient often requires prompt and ac- [Hf]) constitutes alkalemia.* If a and laboratory measurements readily curate interpretation of blood gas patient is noted to have acidosis or obtained in modem hospitals, can values. Such interpretation demands alkalosis it is the physician's respon- easily unravel problems as potenan understanding by the physician *The terms acidemia and alkalemia refer tially confusing as this one. To lay a to the presence of systemic pH values that foundation for the approach that From *the division of nephrology, are below or above the normal range. must be used, let us return for a department of medicine, St. Michael's The terms acidosis and alkalosis refer to moment to some principles of physiHospital and the University of Toronto, specific acid-base disorders and are not and tthe division of nephrology and necessarily accompanied by a correspond- cal and biologic chemistry. the Gage Research Institute, Toronto ing change in pH. In the presence of a Western Hospital An acid is a substance with the mixed acid-base disorder, for example, it Reprint requests to: Dr. Robert A. Bear, is possible for a patient to have metabolic ability to surrender H. in solution; Division of nephrology, Department acidosis and systemic alkalemia. Such a of medicine, St. Michael's Hospital, 30 patient would have coexistent, over-riding conversely, a base is a substance with Bond St., Toronto, Ont. M5B 1W8 the ability to accept this ion. Each respiratory or metabolic alkalosis. CMA JOURNAL/JANUARY 20, 1979/VOL. 120 173

acid in solution exists in equilibrium such as might result from an increase with its conjugate base, a relation de- in the concentration of dissolved CO2. fined by the equation: The ventilatory system maintains the arterial CO2 tension (Pacol) at 40 Acid .-+ Base + H. mm Hg, thereby ensuring that disThe readiness with which an acid solved C02, transported to the lungs gives up H. in solution defines the in buffered form by the blood, is acidity or strength of the acid; the excreted in an amount equal to that converse applies to the alkalinity or produced by cellular metabolism. strength of a base. The bicarbonate buffer system is Although several important acid- also unique in that it is the only buffer systems articulate with the buffer system capable of self-regenextracellular fluid in the human or- eration. In addition to the volatile ganism (H2C03/HCOK, H2P04/ acid (C02) produced as an end-prodHPOr2, H2SO4/SO.2, NH4./NH3, uct of carbohydrate and fat metaboletc.) the "isohydric principle" states ism, approximately 1 mEq/kg body that all buffer pairs in homogeneous weight of nonvolatile acid (sulfuric solution (e.g., plasma) are in equilib- acid. phosphoric acid, uric acid, etc.) rium, with the same [He]. In terms is produced each day in the course of the law of mass action equation of protein and phospholipid metabothe algebraic expression of this prin- lism, and must be excreted by the ciple is: kidney. In the distal tubule H + is dissociated from H2C03 within the [H+] K1 [Acid,] [Base1] = K 2 ]Acid2] [Base2] renal tubular cell; the HC03 thus = K3 [Acid3] created is returned to the general cir[Base3] etc. culation via the renal tubular capilIt should be readily apparent that lary blood, and the H. is secreted this relation permits the clinician to in electroequivalent exchange for analyse perturbations in acid-base Na.. The distal nephron secretion of equilibrium through measurements of H. returns to the extracellular fluid one contributing buffer system; in an the HCO3 that is consumed in the integrated organism, changes in this buffering of nonvolatile acid. buffer system will reflect alterations Let us now analyse how acid-base problems in clinical medicine can be in all other systems. In the clinical assessment of acid- approached and solved through measbase problems the bicarbonate buffer urement of the various components system is the one chosen for meas- of the bicarbonate buffer system. urement. It is the pre-eminent buffer An acid in solution at equilibrium system of extracellular fluid, and. is constantly undergoing association with the use of certain practical as- and dissociation with its conjugate sumptions, all of its components may base. In 1864 the dynamics of such be readily determined. Furthermore, reactions were characterized by the bicarbonate system is unique Guldberg and Waage, who formuamong the body's buffers in that it lated the first expression of the law has an open-ended ventilatory outlet. of mass action. This law states that Approximately 13 000 mmol of dis- for a given set of conditions the ratio solved carbon dioxide enters the sys- of the product of the concentration tem each day as a result of the cellu- of the compounds on one side of lar combustion of carbohydrate and the reaction to the product of the fat. Since dissolved CO2 may be concentration on the other side is a readily hydrated by the ubiquitous constant. The law of mass action enzyme carbonic anhydrase to pro- equation as supplied to the bicarduce carbonic acid (and, therefore, bonate system is referred to as the H.) the daily production of 13 000 Henderson equation: mmol of CO2 carries with it the po[H2C03] [H+] = K [HC031 tential of causing overwhelming acidosis. Fortunately for body economy, Expressed in logarithmic form, in ventilation is increased in response to keeping with the principle of pH, any changes in extracellular fluid pH Henderson's equation achieved wide

174 CMA JOURNAL/JANUARY 20, 1979/VOL. 120

popularity as the Henderson-Hasselbalch equation: pH = pK + log [HCO3j [H2C03]

Since this expression is too unwieldy for ready bedside use, Kassirer and Bleich3 popularized a return to the original Henderson equation in the analysis of clinical acid-base problems. In using this equation the first step is to convert pH into [Hf]; because of a coincidence noted by Kassirer and Bleich this is easily done. They observed that the digits in the mean normal value for plasma [He], 40 nmol/L, are identical to the digits that follow the decimal point in the mean normal blood pH, 7.40. They further noted that in the pH range of 7.10 to 7.50, each change of 1 nmol/L from 40 coincides with the inverse change of approximately 0.01 pH units from 7.40. Accordingly, [Hi] can quickly be computed from the blood pH in the following fashion: pH pH pH pH pH

7.38 7.39 7.40 7.41 7.42

= = = = =

42 41 40 39 38

nmol/L nmol/L nmol/L nmol/L nmol/L

[H+J [H.l [He] [H+] (He]

In the pH ranges 7.28 to 7.10 and 7.45 to 7.50 discrepancies creep into the [H.J value estimated by this method. These discrepancies can be minimized by applying a second observation - namely, that the [Hf] at pH 7.00 is 100 nmol/L, and for each 0.1 pH unit above 7.00 the [Hi] is 80% of the [He] of the previous value. Thus: pH pH pH pH pH pH

7.00 7.10 7.20 7.30 7.40 7.50

= = = = =

100 nmol/L 80 nmol/L 64 nmol/L 51 nmol/L 41 nmol/L 33 nmol/L

[I-i.l (He] [He] [He] [He] [He]

For pH values between those listed above, the [Hf] can be calculated by interpolation. One difficulty with the Henderson equation is that laboratories do not routinely measure the concentration

of either HC03 or H2C03. Fortunately, the total CO2 concentration,

Table I-Normal compensatory adjustments in acid.base disturbances Acute respiratory a.ldosls: A [Hi] = 0.77 A PaCO, IliCOal T 3 to A nimollL Chronic respiratory aci4osla:

A.H+I= 0.3 A Pa.Qg 0.3 A PaCO.

Acute respiratory alkatosis: A 1111 = 0.74 A PaCO2 [I4COg.l . 2 to 3 mmoifL Chronic respiratory alkalosis: . .4.l 0.17 A PaCO2 1HCOsI = 0.5 A PaCO2 Metabolic acl4osis: 1.1 A IHCO8I = A PaCO2 A t anlongap= A I .HCO3-i Metabolic alkalosis:

PaCO, = 0.9 [11C03j

15.6

those in pure respiratory acidosis. Respiratory alkalosis results from any process that tends to reduce the Paco. (except secondary physiologic responses initiated by metabolic acidosis). A reduction in Paco. can be caused by salicylate intoxication, hyperventilation, hyperthyroidism, interstitial pulmonary disease, some central nervous system diseases, chronic liver disease or the administration of progestational agents in short, any event, acute or chronic, that increases alveolar ventilation. For acute respiratory alkalosis Arbus and colleagues6 have constructed a confidence band that shows that, within minutes of the event, each fall of 1 mm Hg in the Paco2 leads to a mean decline in [Hf] of 0.74 nmol/L. The magnitude of this reduction in extracellular [He] for any given acute decrease in Paco. is less than would be expected had a decline in the bicarbonate concentration of the extracellular fluid not occurred. Since renal bicarbonate losses do not occur in acute respiratory alkalosis, and only a slight accumulation of organic acid (lactic acid) has been demonstrated, it is presumed that most of the decline in the bicarbonate concentration of the extracellular fluid can be accounted for by body buffering mechanisms in which hydrogen ions are released from the acid forms of noncarbonic acid buffer systems (one third by blood hemoglobin and two thirds by tissue buffers). Should hyperventilation persist, chronic respiratory alkalosis ensues. and more substantial compensatory mechanisms, mediated by the kidney, are used in defence of the pH. More specifically, it has been shown in dogs that for a sustained fall of I mm Hg in Paco. a mean fall of only 0.17 nmol/L in [He] occurs. A confidence band has been constructed by Gennari, Goldstein and Schwartz7 to illustrate the normal limits of this response. This remarkable degree of compensation is achieved through a Pure respiratory alkalosis decline in renal hydrogen ion excre(acute and chronic) tion apparently mediated through deIn pure respiratory alkalosis the pression of distal tubular exchange changes in acid-base equilibrium are, of Na. for H.. As compensation is in most respects, the opposite of developing, this depression is reCohen;5 the slope of the band is such that [He] rises only a mean of 0.30 nmol/L for each rise of 1 mm Hg in the Paco.. It follows that to satisfy the Henderson equation the serum bicarbonate concentration must also rise 0.30 mmol/L for each increase of 1 mm Hg in the Paco.. Defence of the normal pH, therefore, is better in chronic respiratory acidosis than in acute respiratory acidosis, and is achieved by an increase in the net acid excretion from the kidneys, and, therefore, increased renal generation of bicarbonate. Although the mechanisms are not totally clear, the chronically elevated Pacos apparently stimulates proximal tubular exchange of Na. for H., thereby generating an increase in the serum bicarbonate concentration. Since Na. is being exchanged for H. instead of being reabsorbed with Cl-, increased amounts of Cl- appear in the urine as the adaptive response to chronic respiratory acidosis occurs. Understanding the physiologic events outlined above aids the physician in determining the nature of any respiratory acidosis encountered. For example, given a Paco. of 60 mm Hg, a serum bicarbonate concentration of 27 mmol/L and a pH of 7.24 ([He] 56 nmol/L), one can quickly determine that the rise of 20 mm Hg in Paco. resulted in an increase of 16 nmol/L in [Hi]. The ratio of the change in [Hf] to the change in Paco. of approximately 0.77 and the increase in the serum bicarbonate concentration of only 3 mmol/L are compatible with a pure compensated acute respiratory acidosis. If the Paco. had been 60 mm Hg but the serum bicarbonate concentration 31 mmol/L and the pH 7.34 ([Hf] 46 nmol/L) the ratio of the change in [He] and bicarbonate concentration to that in Paco. of 0.3 would have been most compatible with a pure compensated chronic respiratory acidosis.

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flected by the appearance of increased amounts of sodium in the urine and by a decrease in the serum bicarbonate concentration. Once again, if the Henderson equation is to be satisfied, the serum bicarbonate concentration will fall approximately 1 mmol/ L for each decrease of 2 mm Hg in the Paco. An appreciation of the magnitude of these normal responses to acute and chronic respiratory alkalosis augments the physician's ability to comprehend the nature of any respiratory alkalosis encountered. For example, given a pH of 7.48, a Paco. of 29 mm Hg and a serum bicarbonate concentration of 23 mmol/L, one can see that for a decline of 11 mm Hg in Paco2, [Hf] has fallen 8 nmol/L. The ratio of the change in [Hi to the change in Paco., therefore, is approximately 0.75, and the blood gas values are most compatible with pure compensated acute respiratory alkalosis. Had the Paco. been 29 mm Hg but the pH 7.42 and the serum bicarbonate concentration 19 mmol/L, a change of 11 mm Hg in the Paco2 would have resulted in *a change of 2 nmol/L in [He]. In this case the ratio of the change in [Hi to the change in Paco. of close to 0.17, and the ratio of the change in the bicarbonate concentration to the change in Paco. of close to 0.5 suggests a compensated pure chronic respiratory alkalosis. Pure metabolic acidosis Metabolic acidosis results from any process that tends to reduce the serum bicarbonate concentration (except secondary physiologic responses initiated by respiratory alkalosis). It is clinically convenient to evaluate the patient with metabolic acidosis by determining whether there is an elevation in the concentration of the serum unmeasured anions.8 The concentration of such anions (the "anion gap") is obtained by subtracting the sum of the serum bicarbonate and serum chloride concentrations from the serum sodium concentration. In a healthy individual the unmeasured anions include sulfates, phosphates,

Table tll-.-Clasuification of metabolic acidoses with a normal unmeasured anion gap Underlying problem Disritet Suction from small bowel flttaiae,.so cal drains, ingestIon of aCt,, MgSO. Ureterosigmoldostomy Therap.v wttWoarbonic a Inbibltore Praulma t r Distal renal tabular scidoals Acid administration MCI

"iapwslep&" acidnais I1itflmetab.iftc acldosis (aeetezt)\

Mechanism of acidosla Lossof FlOOr from gut (upa SOutmoift) Loss of 11W3- in or from email bowel

Anion gap Nonnal Normal

Lou of RCO,- in exchange for Cl-In urine draining into uigmeld colon Partial blockage of proximal renal tubular mbsorption of 1100,Inability to reabsorb IlCOrnonnafly in proximal tubele Decreased sold secretion in distal tubule Acid load exceeding ronal excretory ability

Normal Nouwnal Normal Normal Normal

Volume expenuton with solutions frqe of 1100,Metabolic acidoals wIth high unmeasured anIon gap and inset red alensin urine

Normal Observation Normal to Therapy for cause of underlying metabolic slightly acidosis Increased

Treatment Ther,w for diarrhea; FlOOr administration If acidouis Surgical tftera.severe or adjushnent of medication as required; 1100,- administration if acidosis severe HOOf administration; use of ileal loop p favoured as surgical procedure tion discontinued HCOs- and K. replacement lICOr and K. replacement Add administration discontinued

level, and a new steady-state acid- change in the bicarbonate concentra- of chloride ion in the urine during base equilibrium is established. Fur- tion of 1.1 is consistent with pure untreated steady-state alkalemia into thermore, as Lennon and Lemann" metabolic acidosis with respiratory chloride-responsive alkalosis (urine first noted, this decline in Paco2 is compensation. Had the Paco2 been CL concentration 10 to 20 mmol/L highly proportional to the magnitude 28 mm Hg, the pH for the same re- or less) and chloride-resistant alkaof the change in the serum bicar- duction in bicarbonate concentration, losis (urine C1 concentration 10 to bonate concentration, each fall of to 10 mmol/L, would have been 20 mmol/L or more) (Table IV). 1 mmol/L in the latter resulting in 7.15. In this case the ratio of the Metabolic alkalosis secondary to a reduction of 1.1 mm Hg in the change in Paco2 to the change in vomiting or nasogastric suction is the bicarbonate concentration of less prototype of chloride-responsive metformer. Subsequent to this initial respira- than 1.0 speaks for a failure of the abolic alkaloses (other causes are tory compensation, the kidney is respiratory compensatory mechanism diuretic therapy, villous adenoma of mobilized in defence of the pH, and to reduce the Paco2 to an appropriate the colon, congenital chloride-losing renal H. secretion may increase level for this degree of metabolic diarrhea and posthypercapneic metamanyfold. This increase is accom- acidosis. In such a situation one bolic alkalosis). In vomiting or nasopanied by a parallel increase in the speaks of a combined metabolic and gastric suction bicarbonate is gendistal tubular formation and excre- respiratory acidosis even though an erated while loss of chloride from tion of ammonia, which is then avail- absolute elevation of Paco2 does not the stomach induces total body deexist. pletion of chloride, thereby resulting able as a urinary buffer. in a deficiency in the proximal renal Knowing that in a pure compensated state each fall of 1 mmol/L Pure metabolic alkalosis tubular filtrate of an anion suitable in the serum bicarbonate concentrafor reabsorption with sodium. A Metabolic alkalosis results from greater amount of sodium, therefore, tion results in a reduction of 1.1 mm Hg in the Paco2 helps one to deter- any process that tends to elevate the is presented to the distal tubule for mine if a given patient has pure or serum bicarbonate concentration (ex- exchange with H. and K.. Saying mixed metabolic acidosis. With a cept secondary physiologic responses that H. is being secreted is the same pH of 7.28, a Paco2 of 23 mm Hg initiated by respiratory acidosis). For as saying that bicarbonate is being and a serum bicarbonate concentra- diagnostic and therapeutic purposes, absorbed; therefore, continued augtion of 10 mmol/L, for example, the states of metabolic alkalosis are sub- mentation of distal tubular secretion ratio of the change in Paco. to the divided on the basis of the amount of H., along with continued gastric

180 CMA JOURNAL/JANUARY 20, 1979/VOL. 120

loss of hydrochloric acid, perpetuates an elevation in the bicarbonate concentration of extracellular fluid and also leads to a depletion of total body K.. Extracellular fluid concentrations of bicarbonate remain elevated because, as long as volume (and chloride) depletion is present, filtered bicarbonate is reabsorbed along with sodium by the sodium-avid proximal tubule. The accompanying hypokalemia also limits the excretion of filtered bicarbonate. The urine of such patients obviously contains very little chloride. When affected individuals are treated with potassium chloride and sodium chloride the hypokalemia is corrected, sodium is again reabsorbed along with chloride in the proximal tubule, the extracellular fluid volume is restored, and the excretion of excess bicarbonate results in correction of the alkalosis. The mechanism of the acid-base derangements in chloride-resistant metabolic alkalosis is exemplified by adrenal hyperplasia resulting in mmeralocorticoid excess (chloride-resistant metabolic alkalosis can also result from primary hyperaldosteronism, Bartter's syndrome, licorice ingestion, carbenoxolone administration or severe chronic potassium depletion). In this disorder increased mineralocorticoid activity stimulates the distal tubule to reabsorb sodium in exchange for H. and K.. Affected individuals are not volume-depleted, but the faulty hormonal signal increases sodium and hence water reabsorption, which results in unneeded volume expansion; as the perturbed distal tubular Na. reabsorption proceeds, so does H. and K. secretion and hence bicarbonate generation, hypokalemia and alkalosis. The increased volume augments the glomerular filtration rate and increases the amounts of sodium and chloride that are filtered. Since the proximal tubule is not sodium-avid in this instance, less sodium chloride is absorbed, and increased concentrations of chloride appear in the urine. Appropriate therapy obviously does not involve sodium chloride administration but is directed towards the underlying adrenal disorder or ad-

ministration of mineralocorticoid antagonists. As detailed in Table IV, unclassified forms of metabolic alkalosis also exist, including milk-alkali syndrome, situations characterized by decreased effective or true intravascular volume with secondary aldosteronism, sodium carbenicillin therapy, rapid bicarbonate administration, multiple blood transfusions and hypercalcemia related to malignant disease, with release of calcium carbonate from bone. It has been stated that metabolic alkalosis does not result in a compensatory increase in Paco2; however, this is probably incorrect. Several instances have been described in which alveolar ventilation declined in response to metabolic alkalosis, the alkalosis being extreme.11'12 Two authors have recently published confidence bands describing predictable increases in Paco. in response to given elevations in the serum bicarbonate concentration.13'14 The equation of Van Ypersele de Strihou and Frans'4 describing this relationship is: Paco2 = 0.9 [HCO3j + 15.6 Fulop's'3 confidence band is similar. For example, in a patient with metabolic alkalosis and a serum bicarbonate concentration of 40 mmol/L the Paco. would be expected to be 52 mm Hg. Furthermore, a recent report described the untoward effect upon ventilatory function of metabolic alkalosis in patients with chronic obstructive lung disease and CO2 retention.11 Mixed disorders

Thus far, data have been presented that form the basis for quickly differentiating various forms of pure or "uncomplicated" acidoses and alkaloses. However, it is not unusual in clinical practice to confront a number of acid-base imbalances coexisting in a given patient at a given time. In such instances, knowledge of the nature and magnitude of the adaptive mechanisms appropriate to pure acid-base disorders will be valuable in determining the presence and

nature of mixed disturbances. Several examples from previously published reports follow. First, a 47-year-old man with chronic obstructive lung disease was treated with corticosteroids, bronchodilators and a diuretic.'5 Blood gas analysis revealed that the pH was 7.38 ([He] 42 nmol/L), the Paco2 73 mm Hg and the HC03 concentration 45 mmol/L. The most obvious diagnosis was respiratory acidosis, but in applying known relations between respiratory acidosis and the compensatory increase in H. it became evident that something more than "pure.. respiratory acidosis was present. The ratio of the increase in [He] (2 nmol/L) to the increase in Pacol (33 mm Hg) was 0.06. This represented a far greater degree of compensation than one expects in chronic respiratory acidosis, for which the ratio is 0.3. (Similarly, since the ratio of the change in serum bicarbonate concentration to the change in Pacol is also 0.3 in chronic respiratory acidosis, one would expect the serum bicarbonate concentration to have increased by 10 mmol/L, whereas it had risen by 20 mmol/L.) There was, therefore, accompanying metabolic alkalosis, and this was undoubtedly due to diuretic and corticosteroid administration. Furthermore, the diagnosis of this mixed disorder was important clinically, since correction of the metabolic alkalosis led to substantial improvement in the Paco. and the Pao.. Second, a 21-year-old woman with poorly controlled diabetes had the following blood gas and electrolyte values: pH 7.30 ([Hf] 50 nmol/L), HCOr 16 mmol/L, Paco. 32 mm Hg, Na. 138 mmol/L, K. 2.9 mmol/L, Cl- 106 mmol/L and unmeasured anion gap 16 mEq/L.9 Clearly there was evidence of metabolic acidosis, and the ratio of the decrease in Paco. (8 mm Hg) to the decrease in the bicarbonate concentration (8 mmol/L) was close to the 1.1 that one expects in metabolic acidosis with appropriate respiratory compensation. However, in this instance it was apparent that the metabolic acidosis was not due solely to ketoacidosis. While the serum bicar-

CMA JOURNAL/JANUARY 20, 1979/VOL. 120 181

bonate concentration was decreased by 8 mmol/L, the increase in the unmeasured anion gap was only 4 mEq/L (in this patient the normal anion gap was 12 mEq/L). This meant that there was a component of metabolic acidosis with a norma) anion gap in addition to metabolic acidosis caused by the increase in circulating ketoacids. In this case a search for the usual causes of metabolic acidosis with a normal anion gap was unrevealing and further investigations were performed. Ultimately it was determined that the patient was excreting inordinate amounts of p-hydroxybutyrate in the urine. This organic acid is normally highly reabsorbed in the proximal renal tubule and persists in the extracellular fluid as an unmeasured anion. Observation of a dysymmetry between the magnitude of the fall in the serum bicarbonate concentration and the degree to which the unmeasured anion gap was increased therefore led to a diagnosis of underlying metabolic acidosis with a normal unmeasured anion gap and ultimately to documentation of a relatively new form of acid-base disorder. Third, a 56-year-old woman presented to hospital after ingesting an unknown amount of Lugol's iodine in a suicide attempt.16 Six hours after her admission the blood gas and electrolyte values were as follows: pH 7.45 ([WI 35 nmol/L), Paco2 28 mm Hg, HC&r 20 mmol/L, Na. 142 mmol/L, Cl- 101 mmol/L and true anion gap 23 to 25 mEq/L. Since her normal anion gap was 12 mEq/L she had metabolic acidosis with an increased unmeasured anion gap; the concentration of additional unmeasured anions was 11 to 13 mEq/L. This was later found to correspond to a blood lactate value of 13 mmol/L. Remembering that the serum bicarbonate concentration falls 1 mmol/L for each increase of 1 mmol/L above baseline in the concentration of unmeasured anions, one would expect the serum bicarbonate concentration to have been 12 mmol/L. The fact that it was 20 mmol/L means that there was coexistent metabolic alkalosis, in this instance due to intravenous admin-

istration of sodium bicarbonate. Finally, since the ratio of the change in Paco2 to the change in the serum bicarbonate concentration is 1.1 in metabolic acidosis, the decrease in the bicarbonate value of 3 to 4 mmol/L in this patient should have resulted in a Paco2 of about 35 mm Hg. The Paco2 of 28 mm Hg, therefore, indicated coexistent respiratory alkalosis. Conclusion This review has offered a clinical approach to the diagnosis of pure and mixed acid-base disorders. The basis for using the bicarbonate buffer

system to analyse perturbations of acid-base balance was discussed, and the use of the Henderson equation in validating laboratory data was demonstrated. Finally, the predictable compensatory responses to primary acid-base disorders were reviewed and examples were presented to illustrate the value of understanding such relations in diagnosing acute and chronic, pure and mixed acid-base disorders. We thank Ms. Jan Hughes and Mrs. Alita Gibson for typing the manuscript. Dr. Dyck is a fellow of the Medical Research Council of Canada.

7. GENNARI FJ, GOLDSTEIN MB, SCHWARTZ WB: The nature of the renal adaptation to chronic hypocapnia. J Clin Invest 51: 1722, 1972 8. Osi MS, CARROLL HJ: The anion gap. N Engi J Med 297: 814, 1977 9. HAMMEKE M, BEAR R, LEE R, et al: Hyperchioremic metabolic acidosis in diabetes mellitus. Case report and discussion of pathophysiologic mech-

anisms. Diabetes 27: 16, 1978 10. LENNON EJ, LEMANN J Ja: Defense of hydrogen ion concentration in chronic metabolic acidosis. A new evaluation of an old approach. Ann Intern Med 65: 265, 1966 11. OLIVA PB: Severe alveolar hypoventilation in a patient with metabolic alkalosis. Am J Med 52: 817, 1972 12. LsFscmTz MD, BRASCH R, CUOMO AJ, et al: Marked hypercapnia secondary to severe metabolic alkalosis. Ann Intern Med 77: 405, 1972 13. FULOP M: Hypercapnia in metabolic alkalosis. NY State J Med 76: 19, 1976 14. VAN YPERSELE DE STRIHOU C, F1.Ns A: The respiratory response to meta. bolic alkalosis and acidosis in disease.

Gun Sci McI Med 45: 439, 1973 15. BEAR R, GOLDSTEIN M, PHILLIPSON E.

et al: Effect of metabolic alkalosis on respiratory function in patients with chronic obstructive lung disease. Can Med Assoc 1 117: 900, 1977

16. DYCK RF, BEAR RA, GOLDSTEIN MB, et al: Iodine/iodide toxic reaction: case report with emphasis on the nature of the metabolic acidosis. Can Med Assoc J (in press)

BOOKS

References 1. BEAR RA, GRIBIK M: Assessing acidbase imbalances through laboratory parameters. Hosp Pract 9: 157, 1974 2. ARBUS GS: An in vivo acid-base nomogram for clinical use. Can Med Assoc J 109: 291, 1973 3. KASSIRER JP, BLEICH HL: Rapid estimation of plasma carbon dioxide tension from pH and total carbon dioxide content. N Engi J Med 272: 1067, 1965

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SCHWARTZ WB: Carbon dioxide titra. tion curve of normal man. Effect of increasing degrees of acute hypercapnia on acid-base equilibrium. N Engi I Med 272: 6, 1965

5. SCHWARTZ WB, BRACKErr NC JR, COHEN JJ: The response of extracellular hydrogen ion concentration to graded degrees of chronic hypercapnia: the physiologic limits of the defense of pH. 1 Clin invest 44: 291, 1965

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PR, et al: Characterization and clinical application of the "significance band" for acute respiratory alkalosis. N Engi J Med 280: 117, 1969

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continued from page 158 PHYSICAL ACTIVITY AND AGING. Roy J. Shephard. 353 pp. IlIust. Year Book Medical Publishers, Inc., Chicago, 1978. Price not stated. ISBN 0-8151-7646-5 PROGRESS IN MEDICAL VIROLOGY. Vol. 24. Edited by Joseph L. Melnick. 223 pp. Illust. S. Karger AG, Basel, 1978. $54. ISBN 3-8055-2810-8 PSYCHIATRIC CLINICAL SKILLS IN MED. ICAL PRACTICE. The Psychiatric Foundations of Medicine. Ser. 5. Edited by George U. Balis, Leon Wurmser, Ellen McDaniel and others. 492 pp. Butterworth (Publishers). Inc., Woburn, Massachusetts, 1978. Price not stated. ISBN 0-40995110-2 PSYCHIATRIC PROBLEMS IN MEDICAL PRACTICE. The Psychiatric Foundations of Medicine. Ser. 6. Edited by George U. Balis, Leon Wurmser, Ellen McDaniel and others. 473 pp. Butterworth (Publishers), Inc., Woburn, Massachusetts, 1978. Price not stated. ISBN 0-409-951 20-X PSYCHOSOMATIC MEDICINE. Current Trends and Clinical Applications. Edited by Z.J. Lipowski, Don R. Lipsitt and Peter C. Whybrow. 325 pp. Oxford University Press, Don Mills, Ont., 1977. $23.50. ISBN 0-19-502169-X