What is metabolic acidosis?

What is Metabolic Acidosis

Metabolic acidosis is a pathologic acid-base disorder characterized by a primary reduction in serum bicarbonate (HCO₃⁻) below 22 mmol/L, associated with blood pH <7.35, where the body attempts to compensate by increasing ventilation to eliminate CO₂. 1

Core Pathophysiology

Metabolic acidosis develops when the kidney's normal mechanisms for maintaining acid-base homeostasis—elimination of protons and reabsorption/generation of bicarbonate—are overwhelmed or impaired. 2 This occurs through three primary mechanisms:

• Rapid production of nonvolatile acids (e.g., lactic acid, ketoacids) that exceed the body's buffering capacity 2
• Abnormally high bicarbonate losses from the gastrointestinal tract or kidneys 2
• Impaired acid excretion by the kidney, particularly when glomerular filtration rate decreases below 20-25% of normal 3

The normal daily fixed acid load is 50-80 millimoles, which the kidneys excrete while simultaneously regenerating bicarbonate to replenish buffer stores. 4 When this balance is disrupted, acidosis ensues.

Diagnostic Classification: The Anion Gap Approach

The first and most critical step in evaluating metabolic acidosis is calculating the serum anion gap: [Na⁺] − (HCO₃⁻ + Cl⁻), with normal values of 10-12 mEq/L. 5

High Anion Gap Metabolic Acidosis (>12 mEq/L)

An elevated anion gap signifies accumulation of unmeasured organic anions in the body. 5 The primary causes include:

• Lactic acidosis: The predominant contributor in shock states, resulting from inadequate oxygen delivery to tissues and tissue hypoperfusion, with lactate levels indicating tissue hypoxia 5
• Diabetic ketoacidosis (DKA): Characterized by plasma glucose typically >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and positive serum/urine ketones 5
• Alcoholic ketoacidosis: Distinguished from DKA by low or normal plasma glucose (rarely >250 mg/dL) and clinical history of recent heavy alcohol intake 5
• Chronic renal failure: Presents as high anion gap acidosis due to impaired acid excretion by the kidney 5
• Toxic ingestions: Salicylate, methanol, ethylene glycol, and paraldehyde can cause high anion gap metabolic acidosis 5

Normal Anion Gap (Hyperchloremic) Metabolic Acidosis

Normal anion gap acidosis (10-12 mEq/L) results from either bicarbonate loss or ingestion of certain chloride salts. 4 This occurs because:

• Bicarbonate wasting from the gastrointestinal tract (diarrhea) or kidneys (renal tubular acidosis) 6
• Impaired renal acidification where renal input of new bicarbonate is insufficient to regenerate bicarbonate lost in buffering endogenous acid 6
• Recovery phase of diabetic ketoacidosis, as ketoacids are metabolized 1

In these conditions, loss of NaHCO₃ or sodium with unmeasured anions reduces effective extracellular volume, increasing avidity for chloride reabsorption from the diet and resulting in hyperchloremic acidosis. 6

Essential Diagnostic Workup

Beyond the anion gap calculation, several additional tests help pinpoint the etiology:

• Serum or urine ketones are essential to differentiate ketoacidosis from other high-anion-gap etiologies 5
• Plasma glucose assessment aids in distinguishing the type of ketoacidosis: values >250 mg/dL favor DKA, whereas normal-to-low glucose suggests alcoholic ketoacidosis or starvation ketosis 5
• Blood lactate measurement is essential in shock states, with serial measurements providing information about shock severity and treatment response 5
• Osmolal gap can be elevated in methanol, ethylene glycol, and propylene glycol ingestions 5
• Evaluation of renal function (BUN/creatinine) helps identify uremic acidosis as a contributing factor 5

Clinical Manifestations and Compensatory Response

The body attempts to compensate for metabolic acidosis by increasing ventilation to eliminate CO₂, with an expected decrease in PaCO₂ of approximately 1 mmHg for every 1 mmol/L fall in serum HCO₃⁻. 7 This respiratory compensation is critical to survival. 4

Acute Metabolic Acidosis (Minutes to Days)

Adverse effects of acute metabolic acidosis primarily include:

• Decreased cardiac output and arterial dilatation with hypotension 7
• Altered oxygen delivery and decreased ATP production 7
• Predisposition to arrhythmias and impairment of the immune response 7

Chronic Metabolic Acidosis (Weeks to Years)

The main adverse effects of chronic metabolic acidosis are:

• Increased muscle degradation and protein catabolism, leading to muscle wasting and malnutrition 7
• Abnormal bone metabolism and bone demineralization, contributing to renal osteodystrophy 1
• Growth retardation in children with chronic kidney disease 1
• Accelerated CKD progression when bicarbonate levels remain below 22 mmol/L 1

Chronic Kidney Disease Context

Metabolic acidosis is noted in the majority of patients with chronic kidney disease when GFR decreases to less than 20-25% of normal. 3 The acidosis is generally mild to moderate, with plasma bicarbonate concentrations ranging from 12-22 mEq/L. 3 The metabolic acidosis can be of the high-anion-gap variety, although anion gap can be normal or only moderately increased even with stage 4-5 CKD. 3

Serum bicarbonate should be measured at least every three months for patients with GFR ≤30 ml/min per 1.73 m², with a treatment goal of maintaining levels ≥22 mmol/L. 1

Mixed Acid-Base Disorders

In critically ill patients, concurrent high-anion-gap and normal-anion-gap metabolic acidosis are common; clinicians should actively search for mixed disorders rather than assuming a single cause. 5 For example, septic shock exhibits complex metabolic acidosis with multiple contributors, including lactic acidosis and hyperchloremic acidosis. 5

Key Clinical Pitfalls

• Do not confuse serum CO₂ on a basic metabolic panel with arterial PCO₂: The CO₂ measurement in a BMP reflects total carbon dioxide content, which is predominantly bicarbonate (70-85%), not respiratory CO₂ 1
• Recognize compensated chronic respiratory acidosis: Elevated bicarbonate (>28 mmol/L) with normal pH indicates long-standing hypercapnia with metabolic compensation, not primary metabolic alkalosis 1
• Avoid treating compensatory bicarbonate elevation: In chronic respiratory acidosis, the elevated bicarbonate is protective and should not be treated directly 1