What are the causes of metabolic acidosis with dyspnea?

Causes of Metabolic Acidosis with Dyspnea

Metabolic acidosis causes dyspnea by stimulating chemoreceptors, which increases respiratory drive as the body attempts to compensate by eliminating CO2 through hyperventilation. 1

Physiological Mechanism

The dyspnea in metabolic acidosis occurs through chemoreceptor stimulation that increases afferent input to respiratory centers, triggering compensatory hyperventilation to lower PaCO2 and partially correct the acidemia. 1 This represents the body's attempt to maintain pH by reducing the respiratory component of the acid-base equation. 2

Primary Causes of Metabolic Acidosis Presenting with Dyspnea

Renal Causes

• Renal failure is a major cause, as impaired kidney function prevents adequate hydrogen ion excretion and ammonia synthesis, leading to acid accumulation. 1, 3
• Renal tubular acidosis causes metabolic acidosis through defective renal acid handling mechanisms. 1
• Chronic kidney disease (CKD) progressively impairs acid excretion, particularly in stages 3-5, where serum bicarbonate should be monitored monthly and maintained ≥22 mmol/L. 3

Tissue Hypoperfusion and Shock States

• Lactic acidosis from shock (septic, cardiogenic, hypovolemic) results from inadequate oxygen delivery to tissues, with lactate levels >2 mmol/L indicating tissue hypoxia and correlating with mortality. 4
• Decreased cardiac output reduces tissue perfusion, leading to anaerobic metabolism and lactic acid production. 1, 4
• Severe heart failure can cause lactic acidosis even without overt shock, particularly in decompensated states. 5

Diabetic and Metabolic Causes

• Diabetic ketoacidosis (DKA) produces high anion gap acidosis from accumulation of beta-hydroxybutyrate and acetoacetate, with bicarbonate 15-18 mmol/L indicating mild DKA and <15 mmol/L indicating moderate-to-severe DKA. 3, 6
• Euglycemic diabetic ketoacidosis can occur with SGLT2 inhibitors (empagliflozin), particularly during acute illness, decreased carbohydrate intake, or insulin dose reduction. 7

Decreased Oxygen Delivery

• Anemia reduces oxygen-carrying capacity, potentially leading to tissue hypoxia and lactic acidosis. 1
• Hemoglobinopathies impair oxygen release to tissues, causing metabolic acidosis through similar mechanisms. 1

Toxin-Related Causes

• Toxic ingestions including ethylene glycol, methanol, and salicylates produce high anion gap metabolic acidosis. 8
• Pyroglutamic acid (5-oxoproline) and propylene glycol are less common but important causes. 8

Gastrointestinal Causes

• Bicarbonate loss from diarrhea or other GI losses causes hyperchloremic (normal anion gap) metabolic acidosis. 8, 2

Nutritional Deficiencies

• Thiamine deficiency can cause lactic acidosis with dyspnea, particularly in patients with heart failure on chronic diuretic therapy, and responds dramatically to 100 mg IV thiamine. 5

Diagnostic Approach

Calculate the anion gap [Na+ - (HCO3- + Cl-)] to categorize acidosis as high anion gap (>12) versus normal anion gap (hyperchloremic). 8, 2 This distinction narrows the differential significantly:

• High anion gap: Think lactic acidosis, ketoacidosis, renal failure, or toxins 8, 2
• Normal anion gap: Consider GI bicarbonate loss, renal tubular acidosis, or early renal failure 8

Measure serum lactate in all patients with unexplained metabolic acidosis and dyspnea, as levels >2 mmol/L indicate tissue hypoperfusion requiring urgent intervention. 4

Obtain arterial blood gas to confirm pH <7.35, bicarbonate <22 mmol/L, and assess respiratory compensation (PaCO2 should decrease ~1 mmHg for every 1 mmol/L fall in bicarbonate). 3, 2

Critical Clinical Pitfalls

• Don't miss euglycemic DKA in patients on SGLT2 inhibitors presenting with dyspnea and acidosis despite normal glucose—check urine ketones. 7
• Consider thiamine deficiency in patients with heart failure on chronic diuretics presenting with unexplained lactic acidosis and dyspnea—treatment is simple, effective, and potentially life-saving. 5
• Recognize that pregnancy increases respiratory drive and can present with compensatory respiratory alkalosis, but true metabolic acidosis in pregnancy warrants urgent investigation. 1
• In CKD patients, bicarbonate <18 mmol/L requires pharmacological treatment and consideration for hospitalization, especially if symptomatic with dyspnea. 3