What are the causes of metabolic acidosis in individuals with underlying medical conditions such as diabetes, kidney disease, or respiratory problems?

Causes of Metabolic Acidosis

Metabolic acidosis arises from four primary mechanisms: increased endogenous acid production, exogenous acid administration, bicarbonate losses, and impaired renal acid excretion. 1

Primary Mechanisms

Increased Endogenous Acid Production

• Diabetic ketoacidosis (DKA) occurs when insulin deficiency leads to ketone body accumulation (acetoacetate and beta-hydroxybutyrate), creating an anion gap metabolic acidosis with glucose typically >250 mg/dL, pH <7.3, and bicarbonate <15 mEq/L 2, 3
• Lactic acidosis results from inadequate oxygen delivery to tissues during shock states (septic, cardiogenic, hypovolemic), with lactate levels >2 mmol/L indicating tissue hypoxia and correlating with mortality 4
• Severe primary lactic acidosis develops during circulatory insufficiency, cardiac arrest, or severe dehydration when anaerobic metabolism predominates 5

Bicarbonate Losses

• Severe diarrhea causes significant bicarbonate loss through gastrointestinal secretions, resulting in normal anion gap (hyperchloremic) metabolic acidosis 5, 6
• Proximal renal tubular acidosis (RTA) leads to urinary bicarbonate wasting when the proximal tubule fails to reabsorb filtered bicarbonate, reducing effective extracellular volume and increasing chloride reabsorption 6

Impaired Renal Acid Excretion

• Chronic kidney disease (CKD) impairs hydrogen ion excretion and ammonia synthesis when GFR decreases to <20-25% of normal, with plasma bicarbonate typically ranging 12-22 mEq/L 7
• Distal RTA occurs when the distal tubule cannot adequately acidify urine despite normal bicarbonate reabsorption, failing to regenerate bicarbonate lost in buffering endogenous acid 6
• RTA of renal insufficiency develops as kidney function declines, initially presenting as normal gap acidosis but progressing to anion gap acidosis with severe GFR reductions 6

Exogenous Acid Administration

• Drug intoxications including barbiturates, salicylates, and methyl alcohol poisoning require alkalinization of urine to diminish nephrotoxicity 5
• Hemolytic reactions necessitate urinary alkalinization to reduce nephrotoxicity from hemoglobin breakdown products 5

Distinguishing Renal vs. Extrarenal Causes

Calculate the urine anion gap or osmolal gap to differentiate between renal and extrarenal causes of normal gap metabolic acidosis. 6

• Negative urine anion gap indicates appropriate renal ammonium excretion, suggesting extrarenal bicarbonate loss (diarrhea) 6
• Positive urine anion gap indicates impaired renal ammonium excretion, suggesting renal tubular acidosis 6

Special Populations

Diabetes

• DKA is precipitated by insulin deficiency, infection, or discontinuation of insulin therapy, with stopping insulin for economic reasons being a common precipitant in urban populations 2
• Hyperosmolar hyperglycemic syndrome (HHS) can present with metabolic acidosis, though typically less severe than DKA, requiring glucose maintenance at 250-300 mg/dL until hyperosmolarity and mental status improve 2

Kidney Disease

• Metabolic acidosis develops in the majority of CKD patients when GFR falls below 20-25% of normal, though 20% may maintain near-normal acid-base parameters 7
• Western dietary patterns high in animal protein (containing sulfur-containing amino acids) and low in fruits/vegetables (which provide alkali) exacerbate acid accumulation in CKD 3
• Degree of acidosis correlates with CKD severity, with more severe acidosis at lower GFR values 7

Respiratory Problems

• Septic shock exhibits complex metabolic acidosis from lactic acidosis, hyperchloremic acidosis, and increased strong ion gap 4
• Respiratory compensation may be impaired in severe shock, leading to combined respiratory and metabolic acidosis 4

Clinical Pitfalls

• Do not overlook mixed acid-base disorders: CKD patients recovering from DKA commonly develop transient hyperchloremic non-anion gap metabolic acidosis as chloride from IV fluids replaces ketoanions lost during osmotic diuresis 2
• Anion gap may be normal or only moderately increased even with stage 4-5 CKD, so do not rule out significant acidosis based on anion gap alone 7
• Heavy exercise can cause transient metabolic acidosis in normal individuals through lactic acid accumulation 1