Carbon Dioxide (CO2) (Bicarbonate)
Despite the name, serum CO2 measures BICARBONATE (HCO3⁻) — your blood’s primary buffer that maintains pH between 7.35-7.45. LOW CO2/bicarbonate = metabolic acidosis: DKA (diabetic ketoacidosis), kidney disease, severe diarrhea, lactic acidosis, toxic ingestions. HIGH CO2/bicarbonate = metabolic ALKALOSIS: vomiting, diuretics, COPD compensation. Kidneys regulate bicarbonate — CKD causes chronic acidosis. Different from pCO2 on blood gas (that’s respiratory).
The CO2 test on a standard metabolic panel actually measures bicarbonate (HCO3⁻) — your blood’s primary buffer that keeps pH in the narrow range necessary for life. Despite being called “CO2,” this test reflects the total carbon dioxide content in blood, which exists mainly as bicarbonate. This buffering system works with the lungs and kidneys to maintain blood pH between 7.35 and 7.45, a balance critical for enzymes, cellular function, and survival.
Why does this matter? Bicarbonate levels reveal how well your body maintains acid-base equilibrium. Low bicarbonate (metabolic acidosis) can indicate diabetic ketoacidosis, kidney disease, severe diarrhea, or toxic ingestions. High bicarbonate (metabolic alkalosis) may signal prolonged vomiting, diuretic use, or certain hormonal disorders. Because bicarbonate abnormalities can reflect serious underlying conditions, this simple test provides important diagnostic information.
Understanding your CO2/bicarbonate level helps assess kidney function, detect metabolic disturbances, and monitor chronic conditions like diabetes and chronic kidney disease where acid-base problems are common.
Key Benefits of Testing
CO2/bicarbonate testing provides a window into your body’s acid-base status and is included in every basic and comprehensive metabolic panel. It helps detect metabolic acidosis from diabetes, kidney disease, or toxic exposures, as well as metabolic alkalosis from vomiting, diuretics, or hormonal conditions.
For patients with chronic kidney disease, diabetes, or lung disease, regular bicarbonate monitoring helps track disease progression and guide treatment. The test is also essential for evaluating patients with altered mental status, rapid breathing, or other symptoms suggesting acid-base disturbance.
What Does This Test Measure?
The serum CO2 test measures total carbon dioxide in blood, which includes bicarbonate (HCO3⁻), dissolved CO2, and carbonic acid. Since bicarbonate makes up about 95% of this total, the CO2 result essentially reflects bicarbonate concentration — your blood’s main buffer against acid.
The Bicarbonate Buffer System
Your body constantly produces acid through metabolism — every cell generates CO2 and other acidic byproducts. Without buffering, blood pH would quickly drop to lethal levels. Bicarbonate acts as a chemical sponge, absorbing excess acid (hydrogen ions) to prevent dangerous pH swings. The reaction is simple: bicarbonate combines with hydrogen ions to form carbonic acid, which then breaks down into water and CO2 that the lungs exhale.
This system works in partnership with the lungs and kidneys. The lungs regulate CO2 levels by adjusting breathing rate — faster breathing removes more CO2 and reduces acid. The kidneys regulate bicarbonate by either excreting or regenerating it as needed. Together, these three mechanisms — buffering, respiratory control, and renal regulation — maintain the precise pH balance your body requires.
CO2 vs. Bicarbonate vs. pCO2
These related but different measurements can cause confusion:
- Serum CO2 (on metabolic panel): Total carbon dioxide, mostly bicarbonate — reflects metabolic acid-base status
- Bicarbonate (HCO3⁻): The actual buffer molecule — essentially what serum CO2 measures
- pCO2 (on blood gas): Partial pressure of dissolved CO2 gas — reflects respiratory acid-base status
The serum CO2 on your metabolic panel tells you about the metabolic side of acid-base balance, while pCO2 from an arterial blood gas tells you about the respiratory side. Together they provide the complete picture.
Where Bicarbonate Comes From
The kidneys are the primary regulators of bicarbonate levels. They can generate new bicarbonate when the body is too acidic (acidosis) or excrete excess bicarbonate when the body is too alkaline (alkalosis). The kidneys also reabsorb filtered bicarbonate to prevent its loss in urine. This renal regulation is powerful but slow, taking hours to days to fully compensate for acid-base disturbances.
Why This Test Matters
Detects Metabolic Acidosis
Low bicarbonate indicates metabolic acidosis — too much acid or too little buffer in the blood. This is a common and important finding that can indicate serious conditions. Diabetic ketoacidosis (DKA) causes low bicarbonate as ketone acids accumulate. Kidney disease leads to acidosis when failing kidneys can’t excrete acid or regenerate bicarbonate. Severe diarrhea causes bicarbonate loss through the GI tract. Lactic acidosis from shock, sepsis, or tissue hypoxia consumes bicarbonate. Toxic ingestions (methanol, ethylene glycol, salicylates) generate acids that overwhelm buffering capacity.
Detects Metabolic Alkalosis
High bicarbonate indicates metabolic alkalosis — too little acid or excess buffer. Prolonged vomiting loses stomach acid, leaving excess bicarbonate behind. Diuretic medications (especially thiazides and loop diuretics) can cause bicarbonate retention. Excess aldosterone (from adrenal tumors or other causes) increases renal bicarbonate reabsorption. Severe hypokalemia and excessive antacid use are additional causes.
Monitors Kidney Function
The kidneys are responsible for bicarbonate regulation, so bicarbonate levels help assess renal function. Chronic kidney disease commonly causes chronic metabolic acidosis that worsens as kidney function declines. Monitoring bicarbonate in CKD patients guides decisions about alkali supplementation, which may slow disease progression.
Monitors Diabetes
In diabetic patients, falling bicarbonate can signal developing ketoacidosis — a medical emergency. Regular metabolic panels help catch this early, and bicarbonate is part of assessing DKA severity and tracking response to treatment.
Evaluates Respiratory Compensation
When the lungs have chronic problems affecting CO2 elimination (like COPD), the kidneys compensate by retaining bicarbonate. Elevated bicarbonate in a patient with lung disease suggests chronic respiratory acidosis with appropriate metabolic compensation.
Value of Regular Monitoring
Including bicarbonate in your annual or twice-yearly wellness bloodwork establishes your personal baseline. Some individuals run slightly higher or lower than average, and knowing your typical value makes it easier to recognize significant changes. For patients with diabetes, kidney disease, or conditions affecting acid-base balance, regular monitoring catches problems early when they’re most treatable.
What Can Affect CO2/Bicarbonate Levels?
Causes of Low CO2/Bicarbonate (Metabolic Acidosis)
Increased acid production overwhelms buffering capacity:
- Diabetic ketoacidosis (DKA) — ketone acids from fat breakdown
- Lactic acidosis — from shock, sepsis, severe exercise, or metformin toxicity
- Starvation ketosis — milder than DKA
- Alcoholic ketoacidosis
Decreased acid excretion allows acid to accumulate:
- Chronic kidney disease — can’t excrete daily acid load
- Renal tubular acidosis — specific kidney defect in acid handling
- Acute kidney injury
Bicarbonate loss depletes the buffer directly:
- Severe diarrhea — GI tract secretes bicarbonate-rich fluid
- Intestinal fistulas or drainage
- Certain kidney conditions (proximal RTA)
Toxic ingestions generate acid:
- Methanol, ethylene glycol poisoning
- Salicylate (aspirin) overdose
- Certain medications
Causes of High CO2/Bicarbonate (Metabolic Alkalosis)
Acid loss leaves excess bicarbonate:
- Prolonged vomiting — loses stomach hydrochloric acid
- Nasogastric suction
Increased bicarbonate retention or intake:
- Diuretics (thiazides, loop diuretics) — cause volume contraction and bicarbonate retention
- Excess mineralocorticoids (Conn’s syndrome, Cushing’s) — increase renal bicarbonate reabsorption
- Excessive antacid or bicarbonate intake
- Milk-alkali syndrome
Compensation for chronic respiratory acidosis:
- COPD with CO2 retention — kidneys compensate by raising bicarbonate
- Other chronic lung diseases with hypoventilation
Other causes:
- Severe hypokalemia
- Post-hypercapnic alkalosis (after correcting CO2 retention)
- Bartter and Gitelman syndromes (rare genetic conditions)
Normal Variations
Bicarbonate levels are relatively stable in healthy individuals but can fluctuate slightly with diet, hydration status, and altitude. High-protein diets generate more metabolic acid, potentially lowering bicarbonate slightly. Living at high altitude involves respiratory adaptations that affect acid-base balance. These variations are usually minor and within normal ranges.
When Should You Get Tested?
Symptoms suggesting acid-base disturbance warrant bicarbonate testing — rapid or deep breathing (Kussmaul respirations), confusion, fatigue, nausea, or altered mental status. These symptoms can indicate metabolic acidosis requiring urgent evaluation.
Chronic conditions that affect acid-base balance need regular monitoring. Diabetes mellitus requires monitoring for ketoacidosis risk. Chronic kidney disease commonly causes metabolic acidosis that progresses with declining function. COPD and other chronic lung diseases may have compensatory bicarbonate changes. Heart failure patients on diuretics may develop alkalosis.
Medication monitoring is important for drugs affecting acid-base status. Diuretics (especially loop and thiazide types), metformin (risk of lactic acidosis), topiramate and other carbonic anhydrase inhibitors, and chronic aspirin use all warrant periodic bicarbonate checks.
Routine wellness screening includes bicarbonate as part of the basic and comprehensive metabolic panels, establishing baseline values and detecting unsuspected abnormalities.
Understanding Your Results
CO2/bicarbonate results are reported in milliequivalents per liter (mEq/L) or millimoles per liter (mmol/L). Interpretation requires considering the clinical context and other test results.
Interpreting Low Bicarbonate
Mildly low bicarbonate may be seen with mild chronic kidney disease, chronic diarrhea, or as compensation for chronic respiratory alkalosis (hyperventilation). If the patient is otherwise well, mild reductions may simply warrant monitoring.
Moderately low bicarbonate indicates significant metabolic acidosis requiring investigation. Check for diabetes and ketones, evaluate kidney function, assess for infection or shock, and review medications and possible toxic exposures.
Severely low bicarbonate suggests dangerous acidosis that may require urgent treatment. Diabetic ketoacidosis, severe lactic acidosis, toxic ingestions, and advanced kidney failure can all cause severe depression of bicarbonate.
Interpreting High Bicarbonate
Mildly high bicarbonate is often seen as compensation for chronic respiratory acidosis in COPD patients. It can also occur with mild diuretic-induced alkalosis or excessive antacid use.
Moderately to severely high bicarbonate indicates significant metabolic alkalosis. Evaluate for vomiting or nasogastric suction, review diuretic use, check potassium levels (often low), and assess for mineralocorticoid excess.
The Complete Picture
Bicarbonate alone doesn’t tell the whole story. Full interpretation requires blood pH (from arterial blood gas), pCO2 (respiratory component), anion gap (helps classify acidosis type), and clinical context. A low bicarbonate with low pH confirms metabolic acidosis, while low bicarbonate with high pH suggests compensation for respiratory alkalosis. The pattern of all these values together determines the acid-base diagnosis.
What to Do About Abnormal Results
For Low Bicarbonate (Metabolic Acidosis)
Identify the cause through systematic evaluation. Calculate the anion gap — an elevated anion gap suggests DKA, lactic acidosis, kidney failure, or toxic ingestions. A normal anion gap suggests bicarbonate loss (diarrhea) or renal tubular acidosis. Check glucose and ketones to evaluate for DKA. Assess kidney function with creatinine and GFR. Review medications and consider toxic exposures.
Treat the underlying condition. DKA requires insulin, fluids, and electrolyte management. Lactic acidosis requires treating the underlying cause (sepsis, shock, hypoxia). Kidney disease may benefit from alkali supplementation. Toxic ingestions may need specific antidotes and sometimes dialysis.
Sodium bicarbonate supplementation is sometimes used for severe acidosis but is controversial in some situations (like DKA) where treating the underlying cause is more important.
For High Bicarbonate (Metabolic Alkalosis)
Identify the cause by evaluating for vomiting or GI losses, reviewing diuretic use and dosing, checking potassium (usually low in alkalosis), and assessing volume status. Urine chloride can help distinguish causes — low urine chloride suggests vomiting or diuretic use, while high urine chloride suggests mineralocorticoid excess.
Treat the underlying condition. Stop or reduce offending diuretics if possible. Replace potassium — alkalosis is difficult to correct without addressing hypokalemia. Restore volume with saline if volume-depleted. Address underlying hormonal disorders if mineralocorticoid excess is present.
Related Health Conditions
Diabetic Ketoacidosis (DKA)
DKA is a serious diabetes complication where lack of insulin causes the body to break down fat, producing ketone acids. Bicarbonate drops as these acids are buffered, often falling dramatically. Low bicarbonate is a key diagnostic feature and helps assess severity. Learn more →
Chronic Kidney Disease
As kidneys fail, they lose the ability to excrete acid and regenerate bicarbonate, leading to chronic metabolic acidosis. This worsens as CKD progresses and may accelerate kidney decline. Treatment with alkali supplements may slow progression. Learn more →
COPD
Chronic obstructive pulmonary disease often causes CO2 retention (respiratory acidosis). The kidneys compensate by retaining bicarbonate, resulting in elevated serum CO2 levels. This compensated state maintains near-normal pH despite elevated pCO2. Learn more →
Lactic Acidosis
When tissues don’t receive enough oxygen (shock, sepsis, severe anemia), they produce lactic acid. This rapidly consumes bicarbonate, causing dangerous acidosis. Lactic acidosis is a medical emergency requiring treatment of the underlying cause. Learn more →
Renal Tubular Acidosis
RTA is a group of kidney disorders affecting acid handling without overall kidney failure. Patients develop metabolic acidosis with normal anion gap. Different types involve different tubular defects. Treatment usually involves alkali supplementation. Learn more →
Why Testing Matters
CO2/bicarbonate testing provides essential information about your body’s acid-base balance — a fundamental aspect of physiology that affects every organ system. This simple, inexpensive test included in standard metabolic panels can detect serious conditions like diabetic ketoacidosis, kidney disease, and toxic exposures. Regular monitoring helps manage chronic conditions and catch problems early.
Related Biomarkers Often Tested Together
Basic Metabolic Panel (BMP) — CO2 is one component; includes sodium, potassium, chloride, glucose, BUN, creatinine.
Anion Gap — Calculated from electrolytes; helps classify type of acidosis.
Potassium — Often abnormal alongside bicarbonate disturbances; critical to assess together.
Creatinine and BUN — Kidney function markers; help evaluate renal causes of acid-base problems.
Glucose — Elevated glucose with low bicarbonate suggests DKA.
Arterial Blood Gas (ABG) — Provides pH and pCO2 for complete acid-base assessment.
Note: Information provided in this article is for educational purposes and doesn’t replace personalized medical advice.
Frequently Asked Questions
Despite the name, the CO2 test on metabolic panels measures total carbon dioxide content, which is mostly bicarbonate (HCO3⁻). It reflects your blood’s buffering capacity and acid-base balance, not the CO2 you breathe out.
Low CO2/bicarbonate indicates metabolic acidosis. Common causes include diabetic ketoacidosis, kidney disease, severe diarrhea, lactic acidosis from shock or sepsis, and certain toxic ingestions.
High CO2/bicarbonate indicates metabolic alkalosis or compensation for chronic lung disease. Common causes include prolonged vomiting, diuretic use, COPD with CO2 retention, and excess aldosterone.
Related but different. The CO2 you exhale is gas (measured as pCO2 on blood gas). The CO2 on metabolic panels is mostly bicarbonate dissolved in blood. They’re connected through acid-base chemistry but measured differently.
Metabolic acidosis means blood is too acidic due to excess acid production, decreased acid excretion, or bicarbonate loss. Bicarbonate drops as it buffers the excess acid. Causes include DKA, kidney failure, and severe diarrhea.
Metabolic alkalosis means blood is too alkaline due to acid loss or excess bicarbonate. Bicarbonate rises above normal. Common causes include vomiting (losing stomach acid) and diuretic use.
Failing kidneys can’t excrete daily acid production or regenerate bicarbonate, leading to chronic metabolic acidosis. Bicarbonate gradually falls as CKD progresses, and supplementation may be needed.
Modestly. High-protein diets generate more metabolic acid, potentially lowering bicarbonate slightly. Plant-based diets are more alkaline-forming. However, dietary effects in healthy people usually stay within normal ranges.
References
Key Sources:
- Seifter JL. Integration of acid-base and electrolyte disorders. N Engl J Med. 2014;371(19):1821-1831.
- Kraut JA, Madias NE. Metabolic acidosis: pathophysiology, diagnosis and management. Nat Rev Nephrol. 2010;6(5):274-285.
- Palmer BF, Clegg DJ. Electrolyte and acid-base disturbances in patients with diabetes mellitus. N Engl J Med. 2015;373(6):548-559.