What are the causes of low bicarbonate (HCO3) levels, also known as metabolic acidosis?

From the Guidelines

Low bicarbonate levels in the blood, also known as metabolic acidosis, can result from several causes, including kidney dysfunction, diabetic ketoacidosis, severe diarrhea or vomiting, lactic acidosis, and certain medications. The primary causes of low bicarbonate levels include:

• Kidney dysfunction, where the kidneys fail to properly reabsorb bicarbonate or excrete acid 1
• Diabetic ketoacidosis, where the body produces excessive ketones due to insulin deficiency 1
• Severe diarrhea or vomiting, which leads to loss of bicarbonate-rich fluids 1
• Lactic acidosis from poor tissue oxygenation in conditions like sepsis or cardiac arrest 1
• Certain medications like metformin, salicylates, or some antibiotics 1
• Renal tubular acidosis, a kidney disorder affecting acid-base balance 1
• Excessive alcohol consumption 1 Other causes include starvation, which increases ketone production; poisoning from substances like methanol or ethylene glycol; and severe exercise that produces lactic acid 1. Treatment depends on identifying and addressing the underlying cause, which may include intravenous fluids, sodium bicarbonate supplementation for severe cases, insulin for diabetic ketoacidosis, or discontinuation of causative medications 1. It is suggested that in people with CKD and serum bicarbonate concentrations <22 mmol/l, treatment with oral bicarbonate supplementation be given to maintain serum bicarbonate within the normal range, unless contraindicated 1. Increasing fruit and vegetable intake can also help treat high net endogenous acid production and yield more benefits than sodium bicarbonate supplementation alone 1. Low bicarbonate is concerning because it indicates an acid-base imbalance that can affect multiple organ systems and cellular functions if left untreated 1.

From the Research

Causes of Low Bicarbonate

• Metabolic acidosis is a common disorder that can lead to low bicarbonate levels, characterized by an imbalance in the body's acid-base balance 2
• Lactic acidosis, which can be caused by metformin overdose, is a well-known complication of metformin treatment and can lead to low bicarbonate levels 3, 4
• Diabetic ketoacidosis (DKA) can also lead to low bicarbonate levels, and lactate levels have been found to be elevated in patients with DKA 5
• Bicarbonate wasting and/or impaired renal acidification can also cause chronic metabolic acidosis and low bicarbonate levels 2
• Other causes of low bicarbonate levels include:
  • Overproduction of organic acids such as ketoacids or lactic acid 2
  • Acute kidney injury or renal failure 3, 4
  • Gastrointestinal fluid loss accompanied by the continued use of an angiotensin-converting enzyme inhibitor 3
  • Euglycemic diabetic ketoacidosis (euDKA) due to metformin overdose 4

Relationship Between Metformin and Low Bicarbonate

• Metformin has been found to accumulate in erythrocytes and intestinal cells, resulting in less efficient removal with dialysis and rebound lactic acidosis 3
• Metformin-associated lactic acidosis (MALA) is a rare but serious complication of metformin treatment, and identifying metformin levels may help in diagnosis and management 3
• However, the means to identify metformin levels are not widely available, and patients receiving metformin should be counseled to stop metformin and seek medical care in the setting of illnesses 3

Treatment and Management

• The administration of bicarbonate to treat acute metabolic acidosis is controversial due to a lack of definitive benefit and potential complications 6, 2
• However, the administration of base for the treatment of chronic metabolic acidosis is associated with improved cellular function and few complications 2
• Hemodialysis may be necessary for severe lactic acidosis or MALA to improve outcomes 3, 4