Continuing Education Activity

Acid-base disorders are disturbances in the homeostasis of hydrogen ion concentration in the plasma. Any process that increases the serum hydrogen ion concentration is acidotic. The term acidemia is used to describe an abnormally acidic serum, which can result from respiratory acidosis, characterized by changes in carbon dioxide levels, or metabolic acidosis, influenced by decreased bicarbonate levels. Metabolic acidosis is characterized by an increase in the hydrogen ion concentration in the systemic circulation, resulting in an abnormally low serum bicarbonate level. Metabolic acidosis signifies an underlying disorder that needs to be corrected to minimize morbidity and mortality. This activity describes the risk factors, evaluation, and management of metabolic acidosis, highlighting the role of the interprofessional team in enhancing care delivery for patients affected by this condition.

Objectives:

• Determine the causes of metabolic acidosis.
• Apply the presentation of a patient with metabolic acidosis.
• Compare the treatment options for metabolic acidosis.
• Communicate the importance of enhancing coordination amongst the interprofessional team to enhance the delivery of care to patients with metabolic acidosis.

Introduction

Acid-base disorders, including metabolic acidosis, are disturbances in the homeostasis of plasma acidity. Any process that increases the serum hydrogen ion concentration is a distinct acidosis. The term acidemia is used to define the total acid-base status of the serum pH. For example, a patient can have multiple acidoses contributing to a net acidemia. Its origin classifies acidosis as either respiratory acidosis, which involves changes in carbon dioxide levels, or metabolic acidosis, which is influenced by bicarbonate (HCO₃).[1][2][3]

Metabolic acidosis is characterized by an increase in the hydrogen ion concentration in the systemic circulation, resulting in a serum HCO3 less than 24 mEq/L. Metabolic acidosis is not a benign condition and signifies an underlying disorder that needs to be corrected to minimize morbidity and mortality. The many etiologies of metabolic acidosis are classified into 4 main mechanisms: increased production of acid, decreased excretion of acid, acid ingestion, and renal or gastrointestinal (GI) bicarbonate losses.[4][5][6]

Etiology

Determining the type of metabolic acidosis can help clinicians narrow down the cause of the disturbance. Acidemia refers to a pH less than the normal range of 7.35 to 7.45. Additionally, metabolic acidosis is characterized by a bicarbonate level of less than 24 mEq/L. Further classification of metabolic acidosis is based on the presence or absence of an anion gap, or concentration of unmeasured serum anions. Plasma neutrality dictates that anions must balance cations to maintain a neutral charge. Therefore, sodium (Na), the primary plasma cation, is balanced by the sum of the anions bicarbonate and chloride, in addition to the unmeasured anions, which represent the anion gap. Unmeasured anions include lactate and acetoacetate, which are often among the main contributors to metabolic acidosis.[7][8][9]

• Anion gap (AG) = [Na] –([Cl] + [HCO₃])

Anion gap metabolic acidosis is often caused by anaerobic metabolism and lactic acid accumulation. While lactate is part of many mnemonics for metabolic acidosis, it is important to distinguish that it is not a separate etiology, but rather a consequence of a condition.

Mnemonic for anion gap metabolic acidosis differential: CAT MUDPILES

• C: Cyanide and carbon monoxide poisoning
• A: Arsenic
• T: Toluene
• M: Methanol, Metformin
• U: Uremia
• D: DKA
• P: Paraldehyde
• I: Iron, INH
• L: Lactate
• E: Ethylene glycol
• S: Salicylates

Non-gap metabolic acidosis is primarily caused by the loss of bicarbonate, with the main contributing factors being diarrhea and renal tubular acidosis. Additional and rarer etiologies include Addison’s disease, ureterosigmoid or pancreatic fistulas, acetazolamide use, and hyperalimentation through TPN initiation. GI and renal losses of bicarbonate can be distinguished via urine anion gap analysis:

• Urine AG = Urine Na + Urine K – Urine Cl

A positive value is indicative of renal bicarbonate loss, such as renal tubular acidosis. Negative values are found with non-renal bicarbonate losses, such as diarrhea.

Epidemiology

Metabolic acidosis is a sign of underlying pathology, and while it is not uncommon, especially in acutely ill patients, the overall prevalence in the population is uncertain.

Pathophysiology

Hydrogen ion concentration is determined by acid ingestion, acid production, acid excretion, and renal and GI bicarbonate losses. Buffers such as bicarbonate minimize significant pH alterations.[10][11]

History and Physical

A focused history can elicit potential causes of acid-base disturbances, such as vomiting, diarrhea, medications, possible overdoses, and chronic conditions with a predisposition to acidosis, including diabetes mellitus. 

The physical exam reveals signs unique to each cause, such as dry mucous membranes in the patient with diabetic ketoacidosis. Hyperventilation may also be present as a compensatory respiratory alkalosis to assist with PCO₂ elimination and correction of the acidemia. Compensatory reactions do not completely correct a disturbance to the normal pH range, however.

Evaluation

Interpretation Steps

Acid-base interpretation is crucial for identifying and correcting disturbances in acid-base equilibrium, which have profound consequences for patient health. The following steps use lab values and equations to determine if a patient has metabolic acidosis and any additional acid-base disturbances.

Step 1: pH, determine if the acid-base status is acidemia or alkalemia

Blood pH is maintained within a narrow range to optimize physiological functions. Acid-base equilibrium is achieved within a pH range of 7.35 to 7.45. Blood pH distinguishes between acidemia (pH less than 7.35) and alkalemia (pH greater than 7.45)

Step 2: CO₂, determine if the disturbance is metabolic or respiratory

The pCO₂ determines whether the acidosis is respiratory or metabolic in origin. For a respiratory acidosis, the pCO₂ is greater than 40 to 45 due to decreased ventilation. Metabolic acidosis is due to alterations in bicarbonate, so the pCO₂ is less than 40, since it is not the cause of the primary acid-base disturbance. In metabolic acidosis, the distinguishing laboratory value is a decreased bicarbonate level (normal range: 21 to 28 mEq/L).

Step 3: Determine if there is an anion gap or non-anion gap metabolic acidosis

• AG= Na – (Cl + HCO₃)

The normal anion gap is 12. Therefore, values greater than 12 define an anion gap metabolic acidosis.

Step 4: CO₂, assess if respiratory compensation is appropriate

Respiratory compensation is the physiologic mechanism to help normalize a metabolic acidosis; however, compensation never completely corrects an acidemia. It is essential to determine whether there is adequate respiratory compensation or if another underlying respiratory acid-base disturbance exists. Winter's formula is the equation used to determine the expected CO₂ for adequate compensation.

• Winter’s formula: Expected CO₂ = (Bicarbonate x 1.5) + 8 +/- 2

If the patient’s pCO₂ is within the predicted range, then there is no additional respiratory disturbance. If the pCO₂ is greater than expected, this indicates an additional respiratory acidosis. If the pCO₂ is less than expected, an additional respiratory alkalosis is occurring.

Step 5: Evaluate for additional metabolic disturbances

A delta gap must be determined if an anion gap is present.

• Delta gap = Delta AG – Delta HCO₃ = (AG-12) – (24-bicarbonate)

If the gap is less than -6, then a NAGMA is present.

If the gap is greater than 6, then an underlying metabolic alkalosis is present.

If the gap is between -6 and 6, then only an anion gap acidosis exists.

Treatment / Management

The management of metabolic acidosis should address the cause of the underlying acid-base derangement. For example, adequate fluid resuscitation and correction of electrolyte abnormalities are necessary for sepsis and diabetic ketoacidosis. Other therapies to consider include antidotes for poisoning, dialysis, antibiotics, and bicarbonate administration in certain situations. Refer to the specific conditions for a thorough explanation of the appropriate treatment.

Differential Diagnosis

The differential diagnosis depends on the cause of metabolic acidosis. Etiology of the derangement determines the characteristics that influence the differential diagnosis.

Prognosis

The prognosis of metabolic acidosis depends on the etiology and the acid-base derangement. The prognosis is poor if derangements are large and vitals are unstable.

Pearls and Other Issues

Metabolic acidosis is a clinical disturbance characterized by a pH level less than 7.35 and a low bicarbonate (HCO₃) level. The anion gap helps determine the cause of the metabolic acidosis. An elevated anion gap metabolic acidosis can be caused by salicylate toxicity, diabetic ketoacidosis, and uremia (MUDPILES). Non-Gap metabolic acidosis is due to GI loss of bicarbonate (diarrhea) or a failure of the kidneys to excrete acid.

Lab tests that help evaluate metabolic acidosis include those that assess renal and lung function, as well as electrolytes, venous or arterial blood gases, and toxin levels such as salicylate, if an overdose is suspected. Treatment of metabolic acidosis is case-dependent.

Enhancing Healthcare Team Outcomes

The management of metabolic acidosis should address the cause of the underlying acid-base derangement. Because there are many causes, electrolyte disorders are best managed by an interprofessional team that includes nurses and pharmacists. For example, adequate fluid resuscitation and correction of electrolyte abnormalities are necessary for sepsis and diabetic ketoacidosis. Other therapies to consider include antidotes for poisoning, dialysis, antibiotics, and bicarbonate administration in certain situations. The outcomes depend on the cause, patient morbidity, and response to treatment.

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Disclosure: MacKenzie Burger declares no relevant financial relationships with ineligible companies.

Disclosure: Derek Schaller declares no relevant financial relationships with ineligible companies.