Acid-Base Abnormalities Part I Case File

Acid-Base Abnormalities Part I Case File

Eugene C. Toy, MD, Manuel Suarez, MD, FACCP, Terrence H. Liu, MD, MPH

Case 24

A 56-year-old female patient with an overdose from an unknown drug is admitted  to the ICU with respiratory  failure and a change in mental status. A drug screen is  pending. She has a long psychiatric history. Arterial blood gas (ABG) showed a pH  of 7.43, a  PACO2 of 32 mm Hg, and a PAO2 of 100 mm Hg on a fractional inspired  oxygen concentration (FIO2) of 30%. The electrolyte levels were: sodium (Na+) 145  mEq/L, potassium (K+) 4 mEq/L, chloride (CI-) 1O5 mEq/L, bicarbonate (HCO3)  20 mEq/L. Other blood values were blood urea nitrogen (BUN) 35 mg/dL, creatinine  (Cr) 1.3 mg/d, and serum albumin 4 g/L.

⯈What is the most likely diagnosis? 

⯈What is the acid-base abnormality?

⯈What is the best initial therapy for this disorder?

ANSWER TO CASE 24:

Acid-Base Abnormalities Part I

Summary: This 5 6-year-old woman has taken a medication overdose and is admitted to the ICU. Arterial blood gas (ABO) shows a pH of 7.43, a PACO2 of 32 mm Hg, and a PAO2 of 100 mm Hg on fractional inspired oxygen concentration (FIO2) of 30%. The electrolyte levels were sodium (Na+) 145 mEq/L, potassium (K+) 4 mEq/L, chloride (Cl-) 105 mEq/L, and bicarbonate (HCO3) 20 mEq/L.

• Most likely diagnosis : Aspirin (ASA) overdose.
• Acid-base disorder: Metabolic acidosis with respiratory alkalosis.
• Initial therapy: Hydration with normal saline and fluids containing bicarbonate, with alkalinization of urine and increasing excretion of acidic aspirin.

ANALYSIS

Objectives

1. To describe the pathophysiology of ASA toxicity.
2. To describe a systematic approach to acid-base interpretation.
3. To understand how to treat ASA toxicity.

Considerations

This patient has a classical acid-base disorder of metabolic acidosis with a respiratory alkalosis. The bicarbonate level is 20 mEq/L, indicating a metabolic acidosis process; however, the PCO2 is 32 mm Hg and pH is 7.43 indicating a respiratory alkalosis. Also, the patient's CNS signs and symptoms are very suggestive for ASA overdose. ASA overdose starts with tinnitus, advances to hyperventilation, and finally progresses to metabolic acidosis. This is confirmed with an ASA level. Other drugs should be evaluated as well since patients often take multiple agents in overdose situations. Gastric lavage and activated charcoal are useful in acute ingestion. Severe metabolic derangements can occur, uncoupling oxidative phosphorylation; CNS dysfunction or injury is the most serious and can lead to mental status changes, delirium, or even coma. Severe hypoxemia may result from ASA-related pulmonary edema. Adequate fluid replacement without causing pulmonary edema is prudent. Alkalinization of the urine is important to facilitate urinary excretion of the ASA; this can be accomplished with judicious sodium bicarbonate in the IV fluids. Hemodialysis is indicated for severe toxicity, refractory acidosis, coma or seizures, noncardiogenic pulmonary edema, and renal failure.

Approach To:

Acid-Base Abnormalities

DEFINITIONS

ANION GAP = [Na+] - ([Cl-] + [ HCO3^-] ) Normal 12 ± 2

WINTERS FORMULA: Expected PACO2 = 1 .5 x [HC03-] + 8 ± 2 mm Hg

CORRECTED HCO3 = [measured HC03] + ([measured anion-gap] - 12)

PLASMA OSMOLALITY = 2 x (Na+) + (glucose/18) + (blood urea nitrogen/2.8)

OSMOLAL GAP = Measured osmolality - calculated osmolality

(If > 10 difference indicates presence of unmeasured osmoles)

CLINICAL APPROACH

• • Is the patient acidemic or alkalemic? Acidemic if < 7.38 or alkalemic if >7.42.
• • Is the acid-base disorder primarily metabolic (HCO3) or respiratory/ventilatory (PACO2)?
• • What is the anion gap? Sodium - (Chloride + HCO3) = < 12 ± 2 (albumin >4 G).
• • If a metabolic/respiratory acidosis exists, is there appropriate metabolic/respiratory compensation? See expected compensation Table 24-1.
• • If an anion-gap acidemia is present, is there another preexisting metabolic disturbance?

Use △ Gap △ HCO3 or calculated HCO3 or △/△ ratio.

Application of the stepwise approach to the clinical scenario above:

• Is the patient acidemic or alkalemic? Alkalemic.
• Is the acid-base disorder primarily metabolic, HCO3 or respiratory, CO2? Metabolic acidosis (low HCO3 with gap) caused by ASA is the secondary disorder; a primary respiratory alkalosis (earlier onset) is still present.
• What is the anion gap? 145 - (105 + 20) = 20 (normal 12 ± 2) = YES
• If a metabolic/respiratory acidosis exists, is there an appropriate metabolic/respiratory compensation? No, PACO2 by Winters formula is 20 X 1.5 + 8 (±2) = 3 8 (±2) = 36 to 40
• The PACO2 is 32 and less than expected range of 36 to 40, showing a respiratory alkalosis.
• If an anion-gap acidemia is present, is there a complicating metabolic disturbance? No.

(Reproduced, with permission, from Longo DL,  Fauci AS, Kasper DL,  et al. Harrison's  Principles of Internal Medicine. 18th ed.  New York,  NY: McG raw-Hill Education; 201 2. Table 40-1.)

In metabolic acidosis, the anion gap guides one to the cause and treatment of the acidosis. Metabolic acidosis can be calculated from the amount of HCO3 consumed with a positive anion gap versus the amount of loss of HCO3 with a negative anion gap (Table 24-1).

Example 1: A 47-year-old man with a 3 -day history of severe diarrhea is evaluated because of muscle weakness and dizziness. Laboratory studies show sodium 140 mEq/L, potassium 3.2 mEq/L, chloride 120 mEq/L, and bicarbonate 14 mEq/L. Arterial blood gas studies on room air pH 7.27, PACO2 27 mm Hg, PAO2 77 mm Hg.

What is the acid-base derangement?

A common sense systematic approach to solving acid-base problems involves answering 5 questions:

•Is the patient acidemic or alkalemic? Acidemic
•Is the acid-base disorder primarily metabolic or respiratory? Metabolic acidosis
•What is the anion gap?

140 - (120 + 14) = 06 (normal 12 ± 2)

•If a metabolic/respiratory acidosis exists, is there appropriate metabolic/respiratory compensation? Yes. Using Winters formula the predicted PACO2 for HCO3 of 14 is

14 x 1.5 + 8 = 29 ± 2

equaling a predicted compensated PACO2 27 to 31 mm Hg. Here the PACO2 of 27 mm Hg is in the expected range, so we have a correct amount of respiratory compensation and thus a simple nongap metabolic acidosis.

• If an anion-gap acidemia is present, is there a complicating metabolic disturbance? No.

△ gap 12 - 06 = 6. △ HCO3 24 - 14 = 10. 10 - 6 = 4 (normal ± 6)

    If the △ gap is greater than + 6 a preexisting metabolic alkalosis was present, whereas

    if the △ gap is less than -6, then a preexisting metabolic acidosis is present.

Corrected HCO3 24 ± 6 = [measured HCO3 (14)] + ( [measured anion gap (06)] - 12) = 22

Answer: Non-anion-gap metabolic acidosis with appropriate respiratory alkalosis compensation.

In Example 1, the anion gap = 130 - (100 + 10) = 20, indicates an ion-gap metabolic acidosis. If the primary disturbance is a condition other than metabolic acidosis, the presence of an anion gap reveals a "hidden" metabolic acidosis. Negative charges on proteins account for the missing unmeasured anions (mainly albumin at 4 g = -12 of an anion gap). The presence of either a low albumin level (an anion) or an unmeasured cationic light chain ( eg, multiple myeloma) result in a low anion gap. When the primary disturbance is a metabolic acidosis, the anion gap helps narrow the diagnostic possibilities to an anion-gap acidosis or a non-anion-gap acidosis. Healthy individuals have an anion gap of 12 ± 2 mEq/L. The normal anion gap of 12 is represented by the negative charge of the normal 4 g of albumin or a charge of -3 anions per gram of albumin. The compensatory response to a primary disturbance is predictable and brings the pH back toward normal.

Compensation may be appropriate even if the pH is abnormal. The assessment of compensation helps detect mixed respiratory and metabolic acid-base disturbances. In example 1, the expected PACO2 = [(1.5 x 10 ) + 8] = 23 (±2). Because the measured PACO2 is 23 mm Hg and within the predicted range, respiratory compensation is appropriate, making the diagnosis a metabolic acidosis with appropriate respiratory compensation. If the PACO2 is lower than expected, a secondary respiratory alkalosis is diagnosed; if the PACO2 is higher than expected, a secondary respiratory acidosis is diagnosed. The process for diagnosing a coexisting metabolic disturbance involves calculating the "corrected HCO3" If the corrected HCO3 is <24 ± 6 mEq/L, a coexisting non-anion-gap metabolic acidosis is present. If the corrected HCO3 is > 24 ± 6 mEq/L, a coexisting metabolic alkalosis is present.

This formula is based upon the assumption that the measured anion gap represents in part the bicarbonate that was consumed compensating for the acidosis. If the anion gap is added to the measured bicarbonate concentration and the "normal" anion gap of 12 is subtracted, the result represents the bicarbonate concentration if the anion-gap acidosis were not present.

Anion- Gap Metabolic Acidosis

Anion-gap metabolic acidosis exists when acids associated with an unmeasured anion (such as lactate) are produced or gained from an exogenous source. Common causes of high anion-gap metabolic acidosis include lactic acidosis, ketoacidosis (ethanol, starvation, and diabetes) , uremia, methanol, ethylene glycol, and ASA poisonings. A decrease in bicarbonate concentration and resultant anion-gap metabolic acidosis occur when lactic acid accumulates, as seen in states of tissue hypoperfusion. Drug-induced mitochondrial dysfunction, associated with nucleoside therapy in the treatment of AIDS, can lead to lactic acidosis in the absence of obvious tissue hypoxia (called type 2 lactic acidosis). Tonic-clonic seizures, which are associated with an increased metabolic rate, result in a lactic acidosis that quickly reverses; thus, administration of HCO3 is not needed. Ethylene glycol poisoning causes an anion-gap acidosis and acute renal failure. Clues to ethylene glycol poisoning include an osmolal gap ( >10 difference between measured and calculated osmolality) and urinary calcium oxalate crystals as the cause for the renal failure. Methanol poisoning causes an anion-gap acidosis, osmolal gap, and optic nerve toxicity (formic acid toxicity). Isopropyl alcohol poisoning causes an osmolal gap but no acidosis. An osmolal gap is present when the measured plasma osmolality exceeds the calculated plasma osmolality by > 10 mOsm/kg.

When glucose is in short supply or cannot be utilized, the liver converts free fatty acids into ketones to be used as an alternative energy source. In diabetic ketoacidosis, the decreased insulin activity and increased glucagon activity lead to the formation of aceto acetic acid and β-hydroxybutyric acid, both of which are ketones. The presence of these ketoacids decreases the serum bicarbonate concentration and increases the anion gap. Treatment of anion-gap metabolic acidosis requires reversing the condition that led to the excess acid production. Treatment with bicarbonate is unnecessary, except in extreme cases of acidosis when the pH is < 7.20, a level at which dysrhythmia becomes likely and cardiac contractility and responsiveness to catecholamines and medications are impaired (Table 24-2).

Non-Anion-Gap Metabolic Acidosis

Non-anion-gap metabolic acidosis is also called hyperchloremic metabolic acidosis. This develops because fluids containing sodium bicarbonate are lost or hydrogen chloride (or potential hydrogen chloride) is added to the extracellular fluid. The ensuing hyperchloremic metabolic acidosis will not change the anion gap, because the reduction in the bicarbonate concentration is offset by the increase in chloride. The most common cause of non-anion-gap metabolic acidosis is diarrhea. Diarrhea leads to loss of bicarbonate because the intestinal fluid below the stomach is relatively alkaline. All types of renal tubular acidosis (RTA) cause hyperchloremic nongap metabolic acidosis.

Proximal (type 2) RTA is caused by a reduced capacity of the kidney to reabsorb bicarbonate. Distal (type 1) RTA results from an inability of the renal tubules to generate a normal pH gradient (normal urinary pH < 5.5) due to an inability to excrete hydrogen ions.

Type 4 RTA, commonly associated with diabetes, is a hyperkalemic hyperchloremic metabolic acidosis that is due to hypoaldosteronism or an inadequate renal tubular response to aldosterone. This leads to a reduction in the urinary excretion of potassium and hyperkalemia, which interferes with the renal production of NH4+. The inhibition of renal hydrogen ion excretion caused by aldosterone deficiency leads to a nongap metabolic acidosis.

Bicarbonate therapy is generally indicated in non-anion-gap acidosis, whereas correction of the underlying cause is the primary concern in anion-gap acidosis. Oral bicarbonate (oral citrate solution) is the preferred agent for chronic therapy of nonanion- gap acidosis. The preferred bicarbonate salt for treating hypokalemic RTA is potassium bicarbonate or potassium citrate. For acute presentations, especially in patients with concomitant impaired respiratory function, intravenous bicarbonate therapy may be indicated.

Example 2: A 36-year-old woman is evaluated because of generalized weakness. Laboratory show BUN of 40 mg/dL, creatinine 1.9 mg/dL, Na 130 mEq/L, K 3.0 mEq/L, Cl 85 mEq/L, and HCO3 36 mEq/L. ABG studies on room air reveal pH of 7.58, PACO2 of 42 mm Hg, and PAO2 of 90 mm Hg. Urinary electrolytes showed Na 50 mEq/L, K 30 mEq/L, and Cl concentration of 10 mEq/L.

        What is the acid-base derangement?

• Is the patient acidemic or alkalemic? Alkalemic
• Is the acid-base disorder primarily metabolic or respiratory ? Metabolic (high HCO3)
• What is the anion gap? 130 - ( 85 + 36) = 9
• If a metabolic/respiratory acidosis exists, is there appropriate metabolic/respiratory compensation? No, predicted PACO2 is (36 - 24) = 12 x 0.7 = 8.4 + 40 = PACO2 of 48.4. The actual PACO2 is 42 and below the predicted 48, so there is an accompanying respiratory alkalosis.
• If an anion-gap acidemia is present, is there a complicating metabolic disturbance? No, since this is an alkalotic process.

Answer: Combined metabolic and respiratory alkalosis. The elevated arterial pH and HCO3 are consistent with a primary metabolic alkalosis. The arterial PACO2 is inappropriately low for the degree of metabolic alkalosis. Therefore, both metabolic alkalosis and respiratory alkalosis are present.

Metabolic Alkalosis

A primary increase in HCO3 concentration can result from a loss of hydrogen chloride or less commonly, the addition of bicarbonate. This metabolic alkalosis is corrected through urinary excretion of the excess bicarbonate. Increased reabsorption is caused by a contraction of extracellular fluid (ECF), chloride depletion, hypokalemia, or elevated mineralocorticoid activity. The most common causes of metabolic alkalosis are vomiting, nasogastric suction, and diuretic therapy. Table 24-2.

For those cases, which are classified as chloride responsive, the administration of sodium chloride reverses the alkalosis by expanding the intravascular volume and reducing the activity o f the renin-angiotensin-aldosterone axis. This process generates hypokalemia and maintains the metabolic alkalosis. The very low urinary chloride concentration in Example 2 suggests vomiting or remote diuretic ingestion that are correctable by sodium chloride volume expansion. Less commonly, metabolic alkalosis is maintained in the absence of volume depletion. This condition is recognized by a high urinary chloride level ( >20 mEq/L) related to an elevated mineralocorticoid effect. Consequently, these disorders are also called chloride unresponsive or chloride-resistant metabolic alkalosis. H2 blockers and proton pump inhibitors may help to decrease losses of hydrogen ions in patients with prolonged gastric suction or chronic vomiting. Potassium chloride is almost always indicated for the treatment of hypokalemia. In very severe metabolic alkalosis (pH > 7.6), hemodialysis is the preferred treatment. Infusion of acidic solutions is rarely indicated.

CLINICAL CASE CORRELATION

• See also Case 25 (Acid-Base Abnormalities II) and Case 37 (Poisoning).

COMPREHENSION QUESTIONS

24.1  While on call, you are paged by the nurse to evaluate an obese 48-year-old woman admitted for intractable diarrhea and severe dehydration due to Clostridium difficile colitis and exacerbation of her COPD. Her laboratory values were pH 7. 27, PACO2 44 mm Hg, PAO2 50 mm Hg, O2sat 85 % (on FIO2 of 28% ). Na 140 mEqL, K 3.6 mEqL, Cl-118 mEqL, HCO3 18 mEq/L, BUN 45, and creatinine of 1 mg/dL. Urinary chloride is 10 mEq/L. What is the acid-base disturbance?

A. Normal anion-gap metabolic acidosis

B. Chronic respiratory acidosis with metabolic alkalosis

C. Acute respiratory acidosis, uncompensated

D. Acute respiratory acidosis, compensated

E. Metabolic acidosis with hyperosmolar state

24.2  A 64-year-old man is admitted to the intensive care unit with pneumonia and septic shock. Over the past 4 days, he has had an increasing shortness of breath and fever. His only medical problem prior to hospitalization was hypertension. His significant surgical history includes a cholecystectomy. His medications are amlodipine and hydrochlorothiazide. On physical examination, his temperature

is 38.8°C (101.8°F), heart rate is 110 beats/minute, respiration rate is 22 breaths/minute, and blood pressure is 85/50 mm Hg. Other than tachycardia, his cardiac examination is normal. On pulmonary examination, there are crackles over the entire right lung field. Laboratory studies on admission: sodium 136 mEq/L, potassium 4.8 mEq/L, chloride 100 mEq/L, bicarbonate 10 mEq/L. Arterial blood gas studies (on room air): pH 6.94, PCO2 48 mm Hg, PO2 51 mm Hg. Which of the following acid-base conditions is most likely present in this patient ?

A. Anion-gap metabolic acidosis

B. Mixed anion-gap metabolic acidosis and respiratory acidosis

C. Mixed anion-gap metabolic acidosis and respiratory alkalosis

D. Mixed non-anion-gap metabolic acidosis and respiratory acidosis

E. Mixed non-anion-gap metabolic acidosis and respiratory alkalosis

ANSWERS TO QUESTIONS

24.1  A. Normal anion-gap metabolic acidosis (without respiratory compensation)

• Is the patient acidemic or alkalemic? Acidemic
• Is the acid-base disorder primarily metabolic or respiratory? Metabolic (low HCO3)
• What is the anion gap? 140 - (118 + 18) = 4
• If a metabolic/respiratory acidosis exists, is there appropriate metabolic/ respiratory compensation? No, predicted PACO2 is 18 x 1.5 = 27 + 8 = 35 ± 2 (33 to 37) The actual PACO2 is 44 and above the predicted range of 33 to 37 (using Winters formula), s o there i s an accompanying respiratory acidosis.
• If an anion-gap acidemia is present, is there a complicating metabolic disturbance?

Remember, PACO2 and HCO3^- move in the same direction sine they compensate for each other, PACO2 is an acid, HCO3 is a base. The normal PACO2 level is 40 mm Hg and the normal PACO2 level is 44 mm Hg. The HCO3 is lower than 24 without an anion gap, so a nongap hyperchloremic metabolic acidosis is present. The urine chloride is 10 mEq/L. This type of acidosis should respond to aggressive hydration with normal saline. The saline will increase intravascular fluid, which will decrease reabsorption of HCO3 by the proximal tubule.

24.2  B. Mixed anion-gap metabolic and respiratory acidosis. A decrease in the pH and bicarbonate level is consistent with a primary metabolic acidosis. In a patient with a primary metabolic acidosis, a PCO2 that is higher than expected indicates a mixed metabolic and respiratory acidosis. This patient has a mixed anion-gap metabolic acidosis and respiratory acidosis. The pH of 6.94 indicates a life threatening acidosis. This patient requires immediate intubation with mechanical ventilation for oxygenation, and adequate ventilation, since that is the quickest and most reliable means to decrease the PACO2 and increase the pH to a goal of > 7.20. The decreased bicarbonate level accompanied by an elevated anion gap is consistent with an anion-gap metabolic acidosis, most likely due to septic shock-associated lactic acidosis. Winters formula can be used to estimate the expected PCO2 for the degree of acidosis.

CLINICAL PEARLS

⯈In metabolic acidosis the difference of an anion-gap acidosis from a non­gap acidosis directs the treatment.

⯈The treatment of positive-gap acidosis requires a reversal of the underly­ing condition

⯈The treatment of nongap metabolic acidosis depends upon a  replenish­ing of the HCO3 loss.

⯈In type 1 RTA, the distal tubule inability to excrete H+ ions causes loss of urinary HCO3.

⯈Type 2 RTA affects the proximal tubule where HCO3^- fails to be reabsorbed.

⯈In osmolal gaps >10 Osm, consider ethanol, methanol, ethylene glycol, and isopropyl alcohol.

⯈Methanol causes anion-gap hyperosmolal metabolic acidosis and blind­ness by formic acid.

⯈Ethylene glycol causes anion-gap hyperosmolal metabolic acidosis with renal failure and the formation of calcium oxalate stones.

⯈Isopropyl or rubbing alcohol causes a hyperosmolal state but without acidosis.

References

Adrogue HJ, Madias NE. Management of life-threatening acid-base disorders. Part I. N Engl] Med. 1998;338:26-34. 

American College of Physicians. Medical Knowledge Self-Assessment Program 14. Philadelphia, PA: 

American College of Physicians; 2006. American College of Physicians and the Clerkship Directors in Internal Medicine. Internal Medicine Essentials for Clerkship Stuclents. Philadelphia: ACP Press; 2007-2008. 

Loscalzo J. Harrison's Pulmonary and Critical Care Medicine. New York, NY: McGraw Hill; 2011. 

Toy EC, Simon B, Takenaka K, Liu T, Rosh A. Case Files Emergency Medicine. 2nd ed. New York: McGraw-Hill Publishers, 2009.

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