Review Article

Diagnosing Acid-Base Disorders

AK Ghosh Abstract
Diagnosis and management of acid-base disorders ranks high among the medical problems that intimidate many physicians. In practice, acidbase disorders can be approached very systematically as they can be easily diagnosed when certain rules are applied. Using a four step process including, 1) determination the serum pH, 2) calculation of the serum anion gap, 3) estimating the degree of compensation, 4) calculation of the excess anion gap, the reader will be able solve any complex acid-base problem. In this review we describe a practical stepwise approach to identify and resolve issues involving acidbase disorders.

espite the continuous production of acid in the body, perfect homeostasis is maintained by the interplay of various intracellular and extracellular buffers working continuously in perfect harmony with a normal functioning renal and respiratory regulatory system. The normal pH of body is maintained within a narrow range of 7.40 0.05 and any diversion of this range results in an array of serious medical symptoms that bring the patient emergently to the physicians attention. Approaching a patient presenting with acid-base disorder might intimidate many physicians.1 In this review we would describe the practical approach to solve any acidbase disorder. Physicians should be able to interpret acid base disorders problems by following a systematic four step approach. I will describe clues to identify conditions presenting with primary acid base disorders and outline strategies to solve complex disorders by using a systematic approach. In the current review I will discuss the technique to solve simple and complex acid-base problems. For advanced perusal of the topics on the mechanisms of acid base disorders and details of individual acid-base disorders readers are recommended to consult the following reviews.2-6 Initial approach to a patient suspected to have an acid base disorder Approach to an acid-base disorders starts with a good history and physical examination of a patient. Very often the presenting symptoms and signs give us a clue regarding the underlying acid-base disorder. Later in the review I will describe the approach to diagnose the acid-base disorder in a comatose patient. The list of acid base disorders associated with common medical conditions is described in Table 1. For example the primary acid-base disorder in case of vomiting is
Associate Professor, Department of Internal Medicine, Mayo Clinic Rochester, Minnesota, USA. 720

metabolic alkalosis (due to loss of hydrochloric acid in vomiting), while the primary disorder in a patient with diarrhoea is metabolic acidosis (due to loss of bicarbonate in the stool). Physicians need to recognize that very often it is the underlying disorders responsible for the acidbase disorder and not just the pH of the blood that determines the patients status and prognosis.5,6 For example a pH of 7.2 measured in a patient immediately after a seizure could be ignored, however the same pH could suggest a much more worrisome situation in a patient suspected to have ingested ethylene glycol. Additionally, the effects of an acidbase disorder could vary depending on the underlying medical condition of the patient. Effect of alkalosis could have an ominous outcome in a patient with an underlying pulmonary or cardiac disease, as opposed to a patient with panic attack and hyperventilation. The arterial blood gas and common errors in interpretation of patients laboratory data Assessment of the patients acidbase status begins with the measurement of an arterial blood gas (ABG). A common error performed in clinical practice is to comment on the patients acid-base state just from observing the bicarbonate and anion gap in the electrolyte panel. For example once could err in diagnosing normal anion gap acidosis in a patient presenting with low bicarbonate and normal anion gap. However, the most common situation that causes a low bicarbonate in clinical practice is respiratory alkalosis and not normal anion gap metabolic acidosis. Thus one should always look at the ABG first before commenting on the acid-base status of the patient. Corollary while reading ABGs, the reader needs to know that the pH and the PaCO2, is measured directly by the blood gas analyzer, while the bicarbonate value is calculated using the Henderson-Hasselbalch equation. Hence direct
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Table 1 : Acid -base disorders of common medical conditions

Metabolic Acidosis High anion gap Methanol intoxication MUDPILERS Uremia Diabetic ketoacidosis Paraldehyde Isoniazide Lactic acidosis Ethanol Rhabdomyolysis Salicylates Non anion gap GI bicarbonate loss acidosis Diarrhoea Ureteral diversion Renal bicarbonate loss Renal tubular acidosis Aldosterone inhibitors Carbonic anhydrase inhibitors Posthypocapnia Early renal failure Metabolic Alkalosis Urinary chloride low Vomiting, nasogastric suction (chloride sensitive) Diuretic use Posthypercapnia Urinary chloride high Excess mineralocorticoid activity or normal Primary hyperaldosteronism (chloride resistant) Licorice exogenous steroids Cushings disease Bartters syndrome Current or recent diuretic use Excessive alkali administration Refeeding alkalosis Respiratory Acidosis Acute Central nervous system depressiondrugs, CVA, Neuromuscular disease Myasthenia gravis Acute airway obstruction Severe pneumonia Lung injury- flail chest Ventilator malfunction Chronic Chronic obstructive lung disease Chronic respiratory center depression-Pickwician Chronic neuromuscular disorders Respiratory Alkalosis Acute Anxiety Drug use-salicylate, catecholamines, progesterone Hypoxia Pregnancy Sepsis Mechanical ventilation Hepatic encephalopathy CNS system disease

in the review The arterial blood gas (ABG): common trends and compensation pattern in different acid-base states The normal range of pH is 7.35- 7.45, the normal pCO2 is 40 mm of mercury and the normal bicarbonate level is 22-26 mmol/L. Table 2 depicts the expected change in pH, bicarbonate and pCO 2 in primary acid-base disorders. Notice that the expected change occurs in the same direction in primary metabolic disorders and in the opposite direction in primary respiratory disorders. The degree of compensation for simple acid base disorder is described on Table 3. It is important to realize that respiratory compensation for metabolic disorders occur rapidly, however metabolic compensation for respiratory disorders take three to five days.1 Please remember that the primary abnormality lies in the direction of pH disorder. The body does not fully compensate the primary acid-base disorder Serum Anion Gap: clinical uses and reciprocal relation with change in serum bicarbonate After confirmation of the presence of metabolic acidosis, calculation of the serum anion gap is most useful in differential diagnosis of metabolic acidosis disorders (Fig. 1) and differentiating mixed acid-base disorders. The serum anion gap is defined as Na- (Cl- + HCO3-); a normal value is 12 2 meq/L. It measures the unmeasured anion in plasma and includes negatively charged proteins (albumin), phosphates, sulfate and organic anions (such as citrate). The list of the causes for abnormal serum anion gap is outlined in Table 4.
Table 2 : Normal range of pH and alterations in primary acid-base disorders
Disorder Normal Metabolic acidosis Metabolic alkalosis Respiratory acidosis Respiratory alkalosis pH 7.40 decreased increased decreased increased HCO 3 mEq/L 24 decreased increased increased decreased paCO 2 mm Hg 40 decreased increased increased decreased

Table 3 : Compensatory responses in simple acid-base disorders

Disorder Metabolic acidosis Metabolic alkalosis Degree of compensation PaCO 2= (1.5 X HCO3- ) +8 2 PaCO 2 will increase 6 mm Hg for each 10 mEq /L increase in HCO3per 10 mm per 10 mm

measurement of the serum bicarbonate level in the electrolyte panel may be more accurate, though in practical terms the difference between the two measures (i.e., bicarbonate measure in ABG and electrolyte panel respectively) is often minimal. I will also discuss the use of mixed venous blood gas in few clinical situations later
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Respiratory acidosis A cu t e HCO3- will increase 1 meq /L Hg increase in PaCO 2 Chronic HCO3- will increase 4 meq /L Hg increase in PaCO 2 Respiratory alkalosis A cu t e HCO 3- will decrease 2 meq/L Hg increase in PaCO2 Chronic HCO 3- will decrease 4 meq/L Hg increase in PaCO2

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Decrease of serum bicarbonate concentration > increase in serum anion gap Hyperchloremic and anion gap acidosis co-exists Decrease of serum bicarbonate concentration < increase in serum anion gap Complex acid-base disorder An important clinical pearl to differentiate between simple and mixed acid-base disorder is : in contrast to simple disorders, an abnormal value of PaCO2 and bicarbonate in the face of near-normal values of pH should always raise the suspicion of mixed-acid base disorders.
Fig. 1 : Approach to metabolic acidosis with low serum pH.

Table 4 : Causes of abnormal serum anion gap

Increased Anion Gap Frequent * Methanol intoxication Uremia Diabetic ketoacidosis Paraldehyde Isoniazide Lactic acidosis A and B Ethanol Rhabdomyolysis Salicylates Hyperalbuminemia Administered anions Hypoalbuminemia Paraproteinemia (multiple myeloma) Spurious hypercholeremia (Bromide intoxication) Spurious hyponatremia Hypermagnesemia

Infrequent Decreased Anion Gap

*remember MUDPILERS

Urinary Anion Gap Urinary anion gap is used to differentiate between renal 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 urinary ammonium excretion. The normal range is 10 to +10, and represents the amount of unmeasured anions in the urine including sulfates, phosphates, bicarbonates and organic anions like lactate and citrate. These unmeasured anions are accompanied by acid excreted as ammonium. In extra-renal causes of NAG acidosis the kidney produces large amount of ammonium chloride and the urinary anion gap is largely negative ( > -10), in renal causes of NAG metabolic acidosis the kidney is not able to generate ammonium and unable to excrete acid; therefore the urinary anion gap is largely positive (> + 10). Urinary anion gap is useful in patient presenting with normal anion gap acidosis where the patient is not forthcoming with a history of eating disorder or ingestion of laxatives that could cause an extrarenal cause of normal anion gap acidosis (Fig. 1). Osmolar Gap The plasma osmolality can be calculated by the formula 2 X sodium [meq/L] + glucose [ mg/dl] divided by 18 + urea [ mg/dl] divided by 2.8. If the calculated osmolality differ from the measured osmolality by 15 mosm/kg H2O, this is called as osmolar gap and further investigations need to be done. Table 5 gives a list of the causes of osmolar gap. In case of unexplained excess anion gap metabolic acidosis, osmolar gap should be calculated. Excess anion gap acidosis associated with high osmolar gap include ingestion of ethyl gycol, isopropyl alcohol or methanol
Table 5 : Causes of increased osmolar gap
Ethanol Isopropyl alcohol Methanol Glycine Mannitol Ethylene glycol Glycerol Chronic renal failure JAPI VOL. 54 SEPTEMBER 2006

Increase of anion gap may result from other miscellaneous situations like hyperalbuminemia and addition of anions (penicillins). Conversely a decreased anion gap is seen in patients with hypoalbuminemia, paraproteinemia, hypermagnesemia, spurious hypercholeremia (in bromide intoxication) and spurious hyponatremia. In primary acid-base disorders and in a case of simple metabolic acidosis the anion gap will increase by one mEq/L for every 1 mEq/L decrease in serum bicarbonate level (one for one ratio). However this relationship is altered in mixed acid-based disorders due to partial compensatory mechanisms by the kidney and lungs in their effort to maintain homeostais. A comparison in the increment change in anion gap relative to the change in bicarbonate concentration can aid in identifying acidbase disorders. This concept is utilized in the calculation of excess anion gap and diagnose mixed acid-base disorders. Decrease in serum bicarbonate concentration = increase in serum anion gap Primary anion gap metabolic acidosis
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ingestion, and uremia. Hence in a comatose patient presenting in the emergency room, evaluation should include measurement of ABG, serum osmolality, osmolar gap and a toxicology screen to evaluate for drug and alcohol ingestion. Four steps to solve acid-base disorders Having gone over the basic rules of acid-base compensation and pattern of change of PaCO2 and bicarbonate in metabolic (same direction) and respiratory disorders (opposite direction), we are now ready to go over the four steps of solving any acidbase problem. Using a four step process including, 1) determination the serum pH, 2) calculation of the serum anion gap, 3) estimating the degree of compensation, 4) calculation of the excess anion gap, the reader will be able solve any complex acid-base problem (Table 6). I will use a case to demonstrate the use of these 4 steps to solve a acid base question. Case : A 48-year-old male was brought to the emergency room with a history recent obtundation. He has a history of alcoholism and a witnessed grand mal seizure just prior to his arrival. His blood pressure is 128/70 mm Hg, and heart rate was 114/mt. There was no improvement in mental status despite thiamine and dextrose infusion. His electrolyte panel revealed a serum sodium 137 meq/L, potassium 5.0 meq/L, chloride was 100 meq/L, HCO3- was 12 meq/L , creatinine was 4.2 mg/dl. His ABG revealed a pH 7.12, and PaCO2 was 40 mm Hg. Was is the acid-base disorder? And what could be the potential causes for the patients condition? Answer : From the history you suspect possible alcohol related problems, withdrawal or intoxication? Could he have ingested something else? You probably will get a toxic screen and get a serum osmolality to calculate the osmolar gap. You proceed to stabilize the patient and solve the acid base 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 anion gap acidosis, remember any AG > 20 indicates that the primary defect is metabolic acidosis (are you thinking of MUDPILERS?). Please note that you could use the serum HCO-3 level here to calculate anion gap. Step 3. Compensation step: Primary acid-base disorder was metabolic acidosis you apply the formula : calculated PaCO2 = (1.5X12) + 8 2 = 26 2 = 24 to 28 mm Hg; however patient measured PaCO2 was 40 mm Hg hence patient also has associated respiratory acidosis Step 4. Calculate excess anion gap Calculated HCO3 -= (patient anion gap- normal anion gap) + patients HCO3= (25-12) + 12 = 25 meq/L
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Answer : Metabolic with respiratory acidosis with acute renal failure, possible cause pending results methanol intoxication, or ethylene glycol ingestion and uremia. The patient was urgently administered 5 ampoules of sodium bicarbonate, 50 mEq/L per 50 ml intravenously and the following laboratory test was obtained : 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 disorder now ? Using the steps outlined in Table 6, we do the calculations again: Step 1 : pH is 7.47 patient has alkalosis Step 2 : Anion gap was 150 - (26 + 99) = 25, high anion gap acidosis, AG > 20 primary defect is still
Table 6 : Four steps to solve acid-base problems
Step 1. Determine the pH status Acidic pH < 7.35 Alkalemia pH > 7.45 The primary abnormality lies in the direction of pH disorder The body does not fully compensate the primary acid-base disorder Step 2. What is the Anion gap? Calculate the Anion gap. If anion gap > 20 mmol/L there is a primary metabolic acidosis regardless of the bicarbonate level Step 3. What is the degree of compensation? Metabolic acidosis Calculated PaCO 2 = (1.5X HCO3 -) + 8 2 mm Hg If calculated PaCO2 is lower than measured PaCO2 then there is associated Respiratory acidosis If calculated PaCO2 is higher than measured PaCO2 then there is associated Respiratory alkalosis Metabolic alkalosis Increase in paCO2= 0.6 X increase in HCO3Respiratory Acidosis Acute For every 10mm Hg increase in paCO 2, there is 1 meq/L increase in HCO3Chronic For every 10mm Hg increase in paCO2, there is 4 meq/L increase in HCO3Respiratory Alkalosis Acute For every 10mm Hg decrease in paCO2, there is 2 meq/L decrease in HCO3Chronic For every 10mm Hg decrease in paCO2, there is 4 meq/L decrease in HCO3 Step 4. What is the excess anion gap? Calculate the excess anion gap(total anion gap normal anion gap [12 mmol/L]) and add this value to the measured bicarbonate concentration. If the calculated HCO 3- > 30 mmol/L there is associated metabolic alkalosis If the calculated HCO 3- < 23 mmol/L there is associated nonanion gap acidosis In primary acid base disorders; change in anion gap= change in bicarbonate level 723

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metabolic acidosis. Step 3 : Primary acid-base disorder was metabolic acidosis regardless of pH or serum bicarbonate you apply the formula : calculated PaCO2= ( 1.5 X 26) + 8 2 = 47 2 = 45 to 49 mm Hg; however patient PaCO2 was 40 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 respiratory acidosis Step 4. Calculate excess anion gap Calculated HCO3- = (patient anion gap- normal anion gap) + patients HCO3= (25 -12) + 26 = 39 meq/L Calculated HCO3- is greater that 30 meq/L, patient now also has metabolic alkalosis from the bicarbonate infusion. Answer: You just discovered a triple disorder! Metabolic with respiratory acidosis and metabolic alkalosis (beware of bicarbonate infusion as patients respiration could be compromised further) Indication of obtaining mixed venous gas In patients with profound depression of cardiac and pulmonary circulation, but with preservation of alveolar ventilation, for example patient undergoing cardiopulmonary resuscitation, arterial blood gas could reveal arterial hypocapnia, due to increased ventilation: perfusion ratio causing larger than normal removal of carbon dioxide per unit of blood in the pulmonary circulation, thereby falsely indicating arterial hypocapnia, when in reality there is an absolute increase in carbon dioxide. This form of arterial hypocapnia is called pseudorespiratory alkalosis when in reality it is

respiratory acidosis.7 Sampling of mixed venous (central blood) can help in establishing the correct diagnosis of respiratory acidosis in this kind of situation. Accurate diagnosis of this condition is indicated as treatment lies in optimizing the systemic hemodynamic condition.

CONCLUSION
Acid base disorders are commonly encountered by physicians. Taking a good history and physical examination along with a step-wise approach to solving primary and complex acid-base disorders, physicians would be able to identify acid-base disorders associated with serum and urinary anion gap, osmolar gap and identify indications for obtaining a mixed venous blood gas.

REFERENCES
1. 2. Haber RJ. A practical approach to acid-base disorders. West J Med 1991;155:146-51. Madias NE, Perrone RD. Acid-base disorders in association with renal disease. In: Schrier RW, Gottschalk CW, eds. Diseases of the Kidney. 5 th ed. Boston:Little Brown, 1993;3:2669-99. Madias NE, Androgue HJ. Respiratory alkalosis and acidosis. In: Seldin DW, Giebisch G, eds. The Kidney : Physiology and Pathophysiology. 3 rd Ed. New York: Raven Press, 2000: 2131-66. Gluck SL. Acid-base. Lancet 1998;352;474-79. Androgue HJ, Madias NE. Management of life-threatening acid-base disorders. N Engl J Med 1998;338:26-34. Androgue HJ, Madias NE. Management of life-threatening acid-base disorders: second of two parts. N Engl J Med 1998;338:107-11. Androgue HJ, Rashad MN, Gorin AB, Yacoub J, Madias NE. Assessing acid-base status in circulatory failure : differences between arterial and central venous blood. N Engl J Med 1989;320:1312-16.

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Announcement
Third Madras Diabetes Research Foundation (MDRF) American Diabetes Association (ADA) Postgraduate Course on Diabetes, at Chennai, India, 6 - 8th October 2006. The Third MDRF-ADA Postgraduate Course on Diabetes will be held from 6th to 8th October 2006 at Chennai, India. The meeting will be hosted by the Madras Diabetes Research Foundation, Chennai. For further details, contact : Dr. V Mohan, (Or) Dr. Rema Mohan, Madras Diabetes Research Foundation and Dr. Mohans Diabetes Specialities Centre, No.4 Conran Smith Road, Gopalapuram, Chennai - 600 086, India. Phone : (91 44) 28359048, 28359051, 28353351; Fax : (91 44) 28350935; E-mail : [email protected] Also visit our website at www.mdrf-ada.com or www.drmohansdiabetes.com fordetails regarding registration etc.

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