Lactic acidosis: Causes, Types, Symptoms and Treatment

Lactic acidosis is a form of high anion gap metabolic acidosis characterized by a serum lactate level >4 mmol/L. It occurs due to:

• Excessive lactate production (often from tissue hypoxia),

• Impaired lactate clearance (commonly hepatic or renal dysfunction),

• Or both mechanisms combined.

It is the most common cause of metabolic acidosis in hospitalized patients.

Pathophysiology

What is Lactic Acid?

• Lactate is the end-product of anaerobic glycolysis, a normal metabolic process where glucose is broken down to pyruvate and then reduced to lactate.

• In anaerobic conditions, pyruvate is converted to lactate via the Embden-Meyerhof pathway.

• The lactate:pyruvate ratio in tissues is about 25:1.

• Lactate is transported to the liver, where it undergoes oxidation to pyruvate and is then converted back to glucose via the Cori cycle.

Lactic Acid Isomers

• L-lactate: The physiologic form produced by human metabolism and the one typically measured clinically.

• D-lactate: Produced by bacterial metabolism; found in excess in patients with short bowel syndrome or a history of gastric bypass surgery.

Types of Lactic Acidosis (Cohen and Woods Classification)

Type A – Hypoxic Lactic Acidosis

• Due to tissue hypoperfusion or hypoxia.

• Associated with:

  • Shock (septic, cardiogenic, hypovolemic)

  • Severe hypoxemia or anemia

  • Cyanosis

  • Cool, mottled extremities

  • Excess catecholamines (e.g., intense exercise, seizures)

Mechanisms:

• Overproduction of lactate due to anaerobic metabolism.

• Underutilization due to impaired hepatic clearance or inhibited gluconeogenesis.

Type B – Non-Hypoxic Lactic Acidosis

• Occurs without clinical signs of hypoperfusion.

• Subtypes:

  • Type B1 – Associated with systemic diseases:

    • Renal failure

    • Hepatic failure

    • Diabetes mellitus

    • Malignancy (e.g., leukemia, lymphoma)

  • Type B2 – Induced by drugs/toxins (see below).

  • Type B3 – Caused by inborn errors of metabolism.

Note: In sepsis, initial lactic acidosis may be Type A (hypoxic), but with resuscitation, ongoing acidosis may persist as Type B due to mitochondrial dysfunction and altered oxidative phosphorylation.

Common Causes of Lactic Acidosis

🔹 Endogenous Causes

• Shock states (hypovolemic, cardiogenic, septic)

• Severe hypoxia

• Liver failure (reduced clearance)

• Renal failure

• Thiamine deficiency

• Uncontrolled diabetes mellitus

• Malignancies

• Acute pancreatitis

• Short bowel syndrome

🔹 Drugs and Toxins (Type B2)

Drug Class/Type	Examples
Antiretrovirals	Zidovudine, Didanosine, Lamivudine, Zalcitabine
Biguanides	Metformin, Phenformin
Alcohols & Glycols	Ethanol, Methanol, Ethylene glycol, Propylene glycol
Analgesics	Paracetamol (Acetaminophen), Salicylates
Beta-agonists	Epinephrine, Ritodrine, Terbutaline
Anticonvulsants	Valproic acid
Others	Isoniazid, Iron, 5-Fluorouracil, Cyanide, Cocaine, Diethyl ether, Propofol, Strychnine, Sorbitol, Xylitol, Halothane, Sulfasalazine

Special Situations

• Starvation Ketoacidosis: Often seen in neonates, pregnancy, lactation, or prolonged fasting.

• Alcoholic Ketoacidosis: Follows binge drinking and chronic malnutrition.

• D-Lactic Acidosis: Occurs in patients with jejunoileal bypass or short bowel syndrome, due to bacterial fermentation of carbohydrates to D-lactate.

• Pyroglutamic Acidemia: Rare cause seen in acetaminophen toxicity due to glutathione depletion.

Clinical Presentation

• Symptoms often reflect the underlying condition causing lactic acidosis.

• May present acutely or progressively, especially in critically ill patients.

• Common signs:

  • Altered mental status

  • Tachypnea (compensatory)

  • Hypotension

  • Cool extremities

  • Cyanosis

  • Nausea, vomiting

In Severe Cases:

• Seizures

• Coma

• Multiorgan failure

• Disseminated intravascular coagulation (DIC)

• Poor prognosis with persistently high lactate

Diagnosis

• Serum lactate >4 mmol/L

• High anion gap metabolic acidosis

  AG = Na⁺ - (Cl⁻ + HCO₃⁻)

• pH typically <7.35 (in metabolic acidosis)

• Evaluate underlying cause through:

  • Drug/toxin history

  • Sepsis screen

  • Organ function panels (renal, liver)

  • Nutritional status (thiamine levels)

Management

1. Treat the underlying cause:

   • Restore perfusion in shock

   • Discontinue causative drugs/toxins

   • Correct hypoxemia

   • Manage infections or organ dysfunction

2. Supportive therapy:

   • Intravenous fluids

   • Oxygen therapy

   • Vasopressors if needed

   • Hemodialysis (for metformin or toxic alcohols)

3. Supplementation:

   • Thiamine in deficiency or suspicion

   • Bicarbonate therapy (controversial, reserved for pH <7.1)

Prognosis

• Dependent on etiology and speed of correction.

• Persistent lactic acidosis in critically ill patients is associated with high mortality.

• Early recognition and aggressive treatment of underlying cause improve outcomes.

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