Despite the continuous production of acid in the body,perfect homeostasis is maintained by the interplayof various intracellular and extracellular buffers workingcontinuously in perfect harmony with a normalfunctioning renal and respiratory regulatory system. Thenormal pH of body is maintained within a narrow rangeof 7.40 ± 0.05 and any diversion of this range results inan array of serious medical symptoms that bring thepatient emergently to the physicians attention.Approaching a patient presenting with acid-basedisorder might intimidate many physicians.1 In thisreview we would describe the practical approach to solveany acid–base disorder. Physicians should be able tointerpret acid base disorders problems by following asystematic four step approach. I will describe clues toidentify conditions presenting with primary acid –basedisorders and outline strategies to solve complexdisorders by using a systematic approach. In the currentreview I will discuss the technique to solve simple andcomplex acid-base problems. For advanced perusal ofthe topics on the mechanisms of acid base disorders anddetails of individual acid-base disorders readers arerecommended to consult the following reviews.2-6

Approach to an acid-base disorders starts with a goodhistory and physical examination of a patient. Very oftenthe presenting symptoms and signs give us a clueregarding the underlying acid-base disorder. Later inthe review I will describe the approach to diagnose theacid-base disorder in a comatose patient. The list of acid–base disorders associated with common medicalconditions is described in Table 1. For example theprimary acid-base disorder in case of vomiting is metabolic alkalosis (due to loss of hydrochloric acid invomiting), while the primary disorder in a patient withdiarrhoea is metabolic acidosis (due to loss ofbicarbonate in the stool).

Physicians need to recognize that very often it is theunderlying disorders responsible for the acid–basedisorder and not just the pH of the blood that determinesthe patient’s status and prognosis.5,6 For example a pHof 7.2 measured in a patient immediately after a seizurecould be ignored, however the same pH could suggest amuch more worrisome situation in a patient suspectedto have ingested ethylene glycol. Additionally, the effectsof an acid–base disorder could vary depending on theunderlying medical condition of the patient. Effect ofalkalosis could have an ominous outcome in a patientwith an underlying pulmonary or cardiac disease, asopposed to a patient with panic attack andhyperventilation.

Associate Professor, Department of Internal Medicine, MayoClinic Rochester, Minnesota, USA.

Assessment of the patient’s acid–base status beginswith the measurement of an arterial blood gas (ABG). Acommon error performed in clinical practice is tocomment on the patients’ acid-base state just fromobserving the bicarbonate and anion gap in theelectrolyte panel. For example once could err indiagnosing normal anion gap acidosis in a patientpresenting with low bicarbonate and normal anion gap.However, the most common situation that causes a lowbicarbonate in clinical practice is respiratory alkalosisand not normal anion gap metabolic acidosis. Thus oneshould always look at the ABG first before commentingon the acid-base status of the patient. Corollary whilereading ABG’s, the reader needs to know that the pHand the PaCO2, is measured directly by the blood gasanalyzer, while the bicarbonate value is calculated usingthe Henderson-Hasselbalch equation. Hence direct measurement of the serum bicarbonate level in theelectrolyte panel may be more accurate, though inpractical terms the difference between the two measures(i.e., bicarbonate measure in ABG and electrolyte panelrespectively) is often minimal. I will also discuss the useof mixed venous blood gas in few clinical situations later in the review.

The normal range of pH is 7.35- 7.45, the normal pCO2is 40 mm of mercury and the normal bicarbonate level is22-26 mmol/L. Table 2 depicts the expected change inpH, bicarbonate and pCO2 in primary acid-basedisorders. Notice that the expected change occurs in the samedirection in primary metabolic disorders and in the oppositedirection in primary respiratory disorders. The degree ofcompensation for simple acid base disorder is describedon Table 3. It is important to realize that respiratorycompensation for metabolic disorders occur rapidly,however metabolic compensation for respiratorydisorders take three to five days.1 Please remember thatthe primary abnormality lies in the direction of pHdisorder. The body does not fully compensate the primaryacid-base disorder

After confirmation of the presence of metabolicacidosis, calculation of the serum anion gap is mostuseful in differential diagnosis of metabolic acidosisdisorders (Fig. 1) and differentiating mixed acid-basedisorders. The serum anion gap is defined as Na- (Cl- +HCO3-); a normal value is 12 ± 2 meq/L. It measures theunmeasured anion in plasma and includes negativelycharged proteins (albumin), phosphates, sulfate andorganic anions (such as citrate). The list of the causes forabnormal serum anion gap is outlined in Table 4.

Increase of anion gap may result from othermiscellaneous situations like hyperalbuminemia andaddition of anions (penicillins). Conversely a decreasedanion gap is seen in patients with hypoalbuminemia,paraproteinemia, hypermagnesemia, spurioushypercholeremia (in bromide intoxication) and spurious hyponatremia

In primary acid-base disorders and in a case of simplemetabolic acidosis the anion gap will increase by onemEq/L for every 1 mEq/L decrease in serum bicarbonatelevel (one for one ratio). However this relationship isaltered in mixed acid-based disorders due to partialcompensatory mechanisms by the kidney and lungs intheir effort to maintain homeostais. A comparison in the‘increment’ change in anion gap relative to the changein bicarbonate concentration can aid in identifying acid-base disorders. This concept is utilized in the calculationof excess anion gap and diagnose mixed acid-basedisorders.

Decrease of serum bicarbonate concentration >increase in serum anion gap

Decrease of serum bicarbonate concentration <increase in serum anion gap

Urinary anion gap is used to differentiate betweenrenal and extra-renal cause of normal anion gap (NAG)metabolic acidosis. The urinary anion gap is defined as(UNa + UK)-UCl and is an indirect estimation of urinaryammonium excretion. The normal range is –10 to +10,and represents the amount of unmeasured anions in theurine including sulfates, phosphates, bicarbonates andorganic anions like lactate and citrate. Theseunmeasured anions are accompanied by acid excretedas ammonium. In extra-renal causes of NAG acidosisthe kidney produces large amount of ammonium chlorideand the urinary anion gap is largely negative ( > -10), inrenal causes of NAG metabolic acidosis the kidney isnot able to generate ammonium and unable to excreteacid; therefore the urinary anion gap is largely positive(> + 10). Urinary anion gap is useful in patient presentingwith normal anion gap acidosis where the patient is notforthcoming with a history of eating disorder oringestion of laxatives that could cause an extrarenalcause of normal anion gap acidosis (Fig. 1).

Osmolar Gap

The plasma osmolality can be calculated by theformula 2 X sodium [meq/L] + glucose [ mg/dl] dividedby 18 + urea [ mg/dl] divided by 2.8. If the calculatedosmolality differ from the measured osmolality by 15mosm/kg H2O, this is called as osmolar gap and furtherinvestigations need to be done. Table 5 gives a list of thecauses of osmolar gap.

In case of unexplained excess anion gap metabolicacidosis, osmolar gap should be calculated. Excess aniongap acidosis associated with high osmolar gap includeingestion of ethyl gycol, isopropyl alcohol or methanol ingestion, and uremia. Hence in a comatose patientpresenting in the emergency room, evaluation shouldinclude measurement of ABG, serum osmolality, osmolargap and a toxicology screen to evaluate for drug andalcohol ingestion.

Table 5 : Causes of increased osmolar gap

Ethanol Isopropyl alcohol Methanol Glycine Mannitol Ethylene glycol Glycerol Chronic renal failure

Having gone over the basic rules of acid-basecompensation and pattern of change of PaCO2 andbicarbonate in metabolic (same direction) and respiratorydisorders (opposite direction), we are now ready to goover the four steps of solving any acid–base problem.Using a four step process including, 1) determinationthe serum pH, 2) calculation of the serum anion gap, 3)estimating the degree of compensation, 4) calculation ofthe excess anion gap, the reader will be able solve anycomplex acid-base problem (Table 6). I will use a case todemonstrate the use of these 4 steps to solve a acid basequestion.

Case : A 48-year-old male was brought to the emergencyroom with a history recent obtundation. He has a historyof alcoholism and a witnessed grand mal seizure justprior to his arrival. His blood pressure is 128/70 mmHg, and heart rate was 114/mt. There was noimprovement in mental status despite thiamine anddextrose infusion. His electrolyte panel revealed a serumsodium 137 meq/L, potassium 5.0 meq/L, chloride was100 meq/L, HCO3- was 12 meq/L , creatinine was 4.2mg/dl. His ABG revealed a pH 7.12, and PaCO2 was 40mm Hg. Was is the acid-base disorder? And what couldbe the potential causes for the patient’s condition?

Answer : From the history you suspect possiblealcohol related problems, withdrawal or intoxication?Could he have ingested something else? You probablywill get a toxic screen and get a serum osmolality tocalculate the osmolar gap.

You proceed to stabilize the patient and solve the acidbase disorders following the 4 steps ( Table 6).

Step 1. pH is 7.12 – patient has acidosis

Step 2. Anion gap was 137- (12+100) = 25, high aniongap acidosis, remember any AG > 20 indicates that theprimary defect is metabolic acidosis (are you thinking ofMUDPILERS?). Please note that you could use the serumHCO-3 level here to calculate anion gap.

Step 3. Compensation step:

Primary acid-base disorder was metabolic acidosisyou apply the formula : calculated PaCO2 = (1.5X12) + 8± 2 = 26 ± 2 = 24 to 28 mm Hg; however patient measuredPaCO2 was 40 mm Hg hence patient also has associatedrespiratory acidosis

Step 4. Calculate excess anion gap

Calculated HCO3 -= (patient anion gap- normal aniongap) + patients HCO3- = (25-12) + 12 = 25 meq/L

Answer : Metabolic with respiratory acidosis with acuterenal failure, possible cause pending results methanolintoxication, or ethylene glycol ingestion and uremia.

The patient was urgently administered 5 ampoulesof sodium bicarbonate, 50 mEq/L per 50 mlintravenously and the following laboratory test wasobtained :

Serum sodium 150 meq/L, potassium 5.0 meq/L,chloride was 99 meq/L, HCO3- was 26 meq/L, pH 7.47,paCO2 was 40 mm Hg was is the acid-base disordernow ?

Using the steps outlined in Table 6, we do thecalculations again:

Step 1 : pH is 7.47 – patient has alkalosis

Step 2 : Anion gap was 150 - (26 + 99) = 25, highanion gap acidosis, AG > 20 primary defect is still metabolic acidosis.

Step 3 : Primary acid-base disorder was metabolicacidosis regardless of pH or serum bicarbonate youapply the formula : calculated PaCO2= ( 1.5 X 26) + 8 ± 2= 47 ± 2 = 45 to 49 mm Hg; however patient PaCO2 was40 mm Hg, patient respiration has not changed, i.e.patient is not hyperventilating, has not been intubated;you cannot discount that the patient still has respiratoryacidosis

Step 4. Calculate excess anion gap

Calculated HCO3- = (patient anion gap- normal aniongap) + patients HCO3-= (25 -12) + 26 = 39 meq/L

Calculated HCO3- is greater that 30 meq/L, patientnow also has metabolic alkalosis from the bicarbonateinfusion.

Answer: You just discovered a triple disorder!Metabolic with respiratory acidosis and metabolic alkalosis(beware of bicarbonate infusion as patients respirationcould be compromised further)

In patients with profound depression of cardiac andpulmonary circulation, but with preservation of alveolarventilation, for example patient undergoingcardiopulmonary resuscitation, arterial blood gas couldreveal arterial hypocapnia, due to increased ventilation:perfusion ratio causing larger than normal removal ofcarbon dioxide per unit of blood in the pulmonarycirculation, thereby falsely indicating arterialhypocapnia, when in reality there is an absolute increasein carbon dioxide. This form of arterial hypocapnia iscalled ‘pseudorespiratory alkalosis’ when in reality it is respiratory acidosis.7 Sampling of mixed venous (centralblood) can help in establishing the correct diagnosis ofrespiratory acidosis in this kind of situation. Accuratediagnosis of this condition is indicated as treatment liesin optimizing the systemic hemodynamic condition.

CONCLUSION

Acid –base disorders are commonly encountered byphysicians. Taking a good history and physicalexamination along with a step-wise approach to solvingprimary and complex acid-base disorders, physicians’would be able to identify acid-base disorders associatedwith serum and urinary anion gap, osmolar gap andidentify indications for obtaining a mixed venous bloodgas.

REFERENCES

1.Haber RJ. A practical approach to acid-base disorders. WestJ Med 1991;155:146-51.

2.Madias NE, Perrone RD. Acid-base disorders in associationwith renal disease. In: Schrier RW, Gottschalk CW, eds.Diseases of the Kidney. 5th ed. Boston:Little Brown,1993;3:2669-99.

3.Madias NE, Androgue HJ. Respiratory alkalosis and acidosis.In: Seldin DW, Giebisch G, eds. The Kidney : Physiology andPathophysiology. 3rd Ed. New York: Raven Press, 2000:2131-66.

4.Gluck SL. Acid-base. Lancet 1998;352;474-79.

5.Androgue HJ, Madias NE. Management of life-threateningacid-base disorders. N Engl J Med 1998;338:26-34.

6.Androgue HJ, Madias NE. Management of life-threateningacid-base disorders: second of two parts. N Engl J Med1998;338:107-11.

7.Androgue HJ, Rashad MN, Gorin AB, Yacoub J, Madias NE.Assessing acid-base status in circulatory failure : differencesbetween arterial and central venous blood. N Engl J Med1989;320:1312-16.