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Quick Reference
  • Normal Range: 22-28 mEq/L (reported as "Total CO2")
  • Critical Values: <10 mEq/L (severe metabolic acidosis) or >40 mEq/L
  • Primary Use: Acid-base status assessment, metabolic disorder evaluation
  • Sample Type: Serum (venous blood)
  • Low HCO3: Metabolic acidosis - calculate anion gap (MUDPILES vs HARDUPS)
  • High HCO3: Metabolic alkalosis - check urine chloride (saline-responsive vs resistant)
  • Key Point: Primary buffer system; always correlate with pH from ABG for complete picture

Test Description

What is Bicarbonate?

Bicarbonate (HCO3-) is the primary buffer system in the blood, playing a central role in maintaining normal pH (7.35-7.45).

What Labs Actually Measure: "Total CO2"

On standard metabolic panels (CMP, BMP), the lab reports "Total CO2" or "CO2," which represents the sum of bicarbonate plus dissolved carbon dioxide:

Total CO2 Components

Total CO2 = HCO3- + dissolved CO2
Total CO2 ≈ HCO3- + (0.03 × PaCO2)

At physiologic pH, HCO3- accounts for ~95% of total CO2, so Total CO2 ≈ HCO3-

The Bicarbonate Buffer System

Key Equation

CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3-

How Bicarbonate Works in Acid-Base Balance

This equilibrium illustrates the relationship between respiratory (CO2) and metabolic (HCO3-) components of acid-base balance:

  • Metabolic component (HCO3-): Controlled by the kidneys (reabsorption and regeneration)
  • Respiratory component (PaCO2): Controlled by the lungs (ventilation)
  • pH: Determined by the ratio of HCO3- to PaCO2
Key Concept: Metabolic vs Respiratory
  • Primary change in HCO3-: Metabolic acidosis or alkalosis
  • Primary change in PaCO2: Respiratory acidosis or alkalosis
  • Compensation: The body adjusts the other component to normalize pH (e.g., hyperventilation lowers CO2 to compensate for metabolic acidosis)
Low Bicarbonate (Metabolic Acidosis)

Low bicarbonate (HCO3- <22 mEq/L) indicates metabolic acidosis, either primary or as compensation for respiratory alkalosis.

Metabolic Acidosis Classification

The first step in evaluating metabolic acidosis is calculating the anion gap:

Anion Gap

Anion Gap = Na+ - (Cl- + HCO3-)

Normal: 8-12 mEq/L (or 10-14 mEq/L if K is included)

Anion Gap Metabolic Acidosis (AG >12)

Accumulation of unmeasured anions (lactate, ketones, toxins, uremic acids):

MUDPILES Mnemonic
  • M - Methanol: Toxic alcohol ingestion (formic acid accumulation)
  • U - Uremia: Advanced kidney failure (GFR <15 mL/min)
  • D - Diabetic ketoacidosis (DKA): Ketones (β-hydroxybutyrate, acetoacetate)
  • P - Propylene glycol: IV medication vehicle (lorazepam, diazepam infusions)
  • I - Isoniazid, Iron, Inborn errors of metabolism
  • L - Lactic acidosis: Type A (tissue hypoxia) or Type B (medications, malignancy)
  • E - Ethylene glycol: Antifreeze ingestion (glycolic/oxalic acid)
  • S - Salicylates: Aspirin toxicity (also causes respiratory alkalosis)

Non-Anion Gap Metabolic Acidosis (Normal AG, Hyperchloremic)

Loss of bicarbonate or impaired renal acid excretion, compensated by chloride retention:

HARDUPS Mnemonic
  • H - Hyperalimentation: TPN with high chloride content
  • A - Acetazolamide, Addison's disease: Carbonic anhydrase inhibitors, adrenal insufficiency
  • R - Renal tubular acidosis (RTA): Types 1, 2, and 4
  • D - Diarrhea: Loss of bicarbonate-rich intestinal fluid (most common cause)
  • U - Ureteral diversions: Ileal conduit, ureterosigmoidostomy
  • P - Pancreatic fistula: Loss of bicarbonate-rich pancreatic fluid
  • S - Saline administration: Large-volume 0.9% NaCl resuscitation

Compensatory Response

In metabolic acidosis, the lungs compensate by hyperventilating to lower PaCO2:

Winter's Formula (Expected PaCO2 in Metabolic Acidosis)

Expected PaCO2 = (1.5 × HCO3) + 8 ± 2

If measured PaCO2 matches expected, compensation is appropriate. If PaCO2 is higher or lower, there's a mixed disorder.

High Bicarbonate (Metabolic Alkalosis)

Elevated bicarbonate (HCO3- >28 mEq/L) indicates metabolic alkalosis, either primary or as compensation for respiratory acidosis.

Mechanisms of Metabolic Alkalosis

Metabolic alkalosis results from:

  • Loss of H+ (acid): Vomiting, NG suction
  • Gain of HCO3-: Exogenous bicarbonate, citrate from blood products
  • Contraction alkalosis: Volume depletion concentrates existing HCO3-
  • Renal H+ loss: Hyperaldosteronism, diuretics

Classification by Chloride Responsiveness

Urine chloride helps categorize metabolic alkalosis and guide treatment:

Saline-Responsive (Urine Cl <20 mEq/L)

Mechanism: Volume depletion → kidneys retain Na and HCO3

Causes:

  • Vomiting/NG suction: Loss of HCl + volume depletion (most common)
  • Diuretics (remote use): Loop or thiazide diuretics discontinued but alkalosis persists
  • Post-hypercapnic alkalosis: After rapid correction of chronic respiratory acidosis
  • Villous adenoma: Chloride-rich diarrhea causing volume depletion

Treatment: IV normal saline (0.9% NaCl) + KCl replacement

Saline-Resistant (Urine Cl >20 mEq/L)

Mechanism: Mineralocorticoid excess or ongoing diuretic use

Causes:

  • Hyperaldosteronism: Primary (Conn's syndrome), secondary (CHF, cirrhosis, renal artery stenosis)
  • Cushing's syndrome: Excess cortisol has mineralocorticoid activity
  • Current diuretic use: Loop or thiazide diuretics (ongoing)
  • Bartter/Gitelman syndrome: Genetic disorders mimicking diuretic effect
  • Licorice ingestion: Glycyrrhizic acid inhibits 11β-HSD, mimicking aldosterone
  • Severe hypokalemia: K <2.0 mEq/L perpetuates alkalosis

Treatment: Treat underlying cause, K replacement, aldosterone antagonists (spironolactone), acetazolamide if severe

Compensatory Response

In metabolic alkalosis, the lungs compensate by hypoventilating to raise PaCO2 (limited by hypoxemia):

Expected PaCO2 in Metabolic Alkalosis

Expected PaCO2 rise = 0.7 × (HCO3 rise)

PaCO2 rarely exceeds 55 mmHg due to hypoxic drive

Compensation and Mixed Disorders

Expected Compensation

Swipe to see more
Primary Disorder Primary Change Compensatory Response Expected Compensation
Metabolic Acidosis ↓ HCO3 ↓ PaCO2 (hyperventilation) PaCO2 = (1.5 × HCO3) + 8 ± 2
Metabolic Alkalosis ↑ HCO3 ↑ PaCO2 (hypoventilation) PaCO2 ↑ by 0.7 × (HCO3 rise)
Respiratory Acidosis (Acute) ↑ PaCO2 ↑ HCO3 (minimal) HCO3 ↑ by 1 per 10 mmHg PaCO2 rise
Respiratory Acidosis (Chronic) ↑ PaCO2 ↑ HCO3 (renal compensation) HCO3 ↑ by 3.5 per 10 mmHg PaCO2 rise
Respiratory Alkalosis (Acute) ↓ PaCO2 ↓ HCO3 (minimal) HCO3 ↓ by 2 per 10 mmHg PaCO2 drop
Respiratory Alkalosis (Chronic) ↓ PaCO2 ↓ HCO3 (renal compensation) HCO3 ↓ by 5 per 10 mmHg PaCO2 drop

Mixed Acid-Base Disorders

Mixed disorders occur when two or more primary acid-base disturbances coexist:

  • Metabolic acidosis + respiratory acidosis: Cardiac arrest (lactic acidosis + hypoventilation)
  • Metabolic acidosis + metabolic alkalosis: Vomiting in DKA (ketoacidosis + HCl loss)
  • High AG acidosis + normal AG acidosis: DKA + diarrhea
  • Triple acid-base disorder: Metabolic acidosis + metabolic alkalosis + respiratory disorder (e.g., vomiting + septic shock + ARDS)
Clinical Pearls
"Total CO2 on CMP ≈ Bicarbonate"

The "CO2" or "Total CO2" on your metabolic panel is essentially bicarbonate (HCO3-). Don't confuse it with PaCO2 from an ABG, which measures dissolved CO2 gas.

Anion gap is your first clue

In metabolic acidosis, always calculate anion gap. High AG = think MUDPILES; normal AG = think HARDUPS.

Diarrhea causes normal AG acidosis

Stool is rich in bicarbonate. Loss of HCO3- → acidosis. Chloride rises to maintain electroneutrality → hyperchloremic, normal AG acidosis.

Vomiting causes metabolic alkalosis

Loss of HCl from gastric fluid → alkalosis. Volume depletion → secondary hyperaldosteronism → K loss and perpetuation of alkalosis.

DKA correction can unmask normal AG acidosis

Patient with DKA often has coexisting diarrhea. After treating DKA and clearing ketones, normal AG acidosis from diarrhea persists.

Use Winter's formula to detect mixed disorders

In metabolic acidosis, if measured PaCO2 is higher than expected (Winter's formula), there's concurrent respiratory acidosis. If lower than expected, there's concurrent respiratory alkalosis.

Lactic acidosis is the most common cause of high AG acidosis

In the ED/ICU, think lactate first. Sepsis, shock, tissue hypoxia are common causes.

Check lactate and ketones in high AG acidosis

Measuring lactate and beta-hydroxybutyrate identifies the most common causes (lactic acidosis and DKA). If both are normal, consider toxins.

Salicylate toxicity causes mixed disorder

Direct stimulation of respiratory center → respiratory alkalosis. Salicylic acid accumulation → metabolic acidosis. Net result: high AG acidosis with low PaCO2.

Contraction alkalosis from diuretics

Loop/thiazide diuretics cause volume contraction, concentrating existing HCO3- → alkalosis. Give saline + KCl to correct.

Severe alkalosis (HCO3 >40) can be life-threatening

Causes hypokalemia, hypocalcemia (ionized Ca drops), arrhythmias, seizures, and tissue hypoxia (leftward shift of O2-Hb curve).

Compensation never overcorrects

Respiratory compensation for metabolic disorders (or vice versa) brings pH toward normal but NEVER makes pH cross to the opposite side. If pH is alkalemic, the primary disorder is alkalosis; if acidemic, it's acidosis.

Check urine chloride to guide alkalosis treatment

Low urine Cl (<20) = saline-responsive (give fluids). High urine Cl (>20) = saline-resistant (treat underlying cause, not more fluids).

References
  1. Kratz, A., Ferraro, M., Sluss, P. M., & Lewandrowski, K. B. (2004). Laboratory reference values. New England Journal of Medicine, 351, 1548-1564.
  2. Lee, M. (Ed.). (2009). Basic skills in interpreting laboratory data. Ashp.
  3. Farinde, A. (2021). Lab values, normal adult: Laboratory reference ranges in healthy adults. Medscape. https://emedicine.medscape.com/article/2172316-overview?form=fpf
  4. Nickson, C. (n.d.). Critical Care Compendium. Life in the Fast Lane • LITFL. https://litfl.com/ccc-critical-care-compendium/
  5. Farkas, Josh MD. (2015). Table of Contents - EMCrit Project. EMCrit Project. https://emcrit.org/ibcc/toc/
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