What are the causes of metabolic acidosis remembered by the MUDPIE (Methanol, Uremia, Diabetic ketoacidosis, Paraldehyde, Isoniazid, Ethylene glycol) pneumonic?

Causes of Metabolic Acidosis Remembered by the MUDPIE Mnemonic

The MUDPIE mnemonic represents key causes of high anion gap metabolic acidosis: Methanol, Uremia, Diabetic ketoacidosis, Paraldehyde, Isoniazid, and Ethylene glycol, each contributing to significant morbidity and mortality through different pathophysiological mechanisms. 1

Detailed Explanation of Each Component

M - Methanol

• Methanol poisoning produces both an anion gap and osmolar gap due to being a low-molecular weight organic compound 2
• Methanol is metabolized via alcohol dehydrogenase to formaldehyde and then to formate, which is the primary toxic metabolite 3
• Formate accumulation is responsible for the metabolic acidosis in early stages of intoxication and can cause tissue hypoxia leading to ocular toxicity 3
• Clinical presentation includes visual disturbances that may progress to visual impairment following a latent period 3

U - Uremia

• Renal failure leads to accumulation of organic acids and impaired acid excretion 2
• Typically presents with elevated BUN, creatinine, and hyperkalemia 2
• Uremia contributes to high anion gap metabolic acidosis through failure to excrete acids produced by normal metabolic processes 4
• Treatment may include bicarbonate supplementation when levels fall below 18 mmol/L in chronic kidney disease 4

D - Diabetic Ketoacidosis

• Results from insulin deficiency with elevated counterregulatory hormones 2
• Diagnostic criteria include blood glucose >250 mg/dL, arterial pH <7.3, bicarbonate <15 mEq/L, and positive ketones 2
• Treatment requires fluid resuscitation, insulin therapy, and electrolyte management 2
• Represents one of the most common causes of high anion gap metabolic acidosis encountered in emergency settings 5

P - Paraldehyde

• Paraldehyde is a less commonly encountered cause in modern practice but remains in the classic mnemonic 1
• Metabolized to acetaldehyde and acetic acid, contributing to metabolic acidosis 5
• Can present with characteristic breath odor and CNS depression 5
• Historically used as a sedative and anticonvulsant but rarely prescribed today 5

I - Isoniazid

• Isoniazid toxicity can cause seizures and metabolic acidosis 1
• Often included alongside iron or inborn errors of metabolism in expanded versions of the mnemonic 6
• Mechanism involves interference with pyridoxine (vitamin B6) metabolism 5
• Treatment includes high-dose pyridoxine administration 5

E - Ethylene Glycol

• Ethylene glycol is metabolized via alcohol dehydrogenase to glycolaldehyde and then to glycolate, which is primarily responsible for the metabolic acidosis 3
• Glycolate is further metabolized to oxalate, which precipitates with calcium in various tissues and urine 3
• Clinical presentation includes renal and cardiopulmonary failure 3
• Treatment involves alkali administration, ethanol as an antimetabolite (competing for alcohol dehydrogenase), and hemodialysis 3

Clinical Approach to High Anion Gap Metabolic Acidosis

• Calculate anion gap using the formula: [Na+] - ([Cl-] + [HCO3-]), with normal being 8-12 mEq/L and high anion gap >12 mEq/L 2
• Consider calculating serum osmolal gap to detect presence of low molecular weight toxins like methanol and ethylene glycol 2
• The MUDPIE mnemonic should be systematically evaluated in patients presenting with unexplained high anion gap metabolic acidosis 1
• Some clinicians now use expanded mnemonics like GOLD MARK (Glycols, Oxoproline, L-lactate, D-lactate, Methanol, Aspirin, Renal failure, and Ketoacidosis) for a more comprehensive approach 6

Important Clinical Considerations

• Early recognition and treatment are critical for improved outcomes in all causes of high anion gap metabolic acidosis 3
• Prognosis is excellent in toxic alcohol poisonings with early treatment including alkali therapy, ethanol as an antimetabolite, and hemodialysis 3
• Multiple causes of metabolic acidosis may coexist, complicating diagnosis and management 7
• For organic acidosis like lactic acidosis, the primary treatment is cessation of acid production via improvement of tissue oxygenation 5
• Laboratory analysis of organic acids can help identify specific causes, particularly in cases of inborn errors of metabolism 8