Bicarbonate (HCO₃⁻): Overview and Practice Questions (2025)

Bicarbonate (HCO₃⁻) is a crucial electrolyte in the human body that plays an essential role in maintaining acid-base balance. While it might be overlooked compared to oxygen or carbon dioxide, bicarbonate is vital to the practice of respiratory therapy.

Understanding how bicarbonate functions can help respiratory therapists make better clinical decisions, particularly when interpreting arterial blood gases (ABGs) or managing patients with respiratory or metabolic disorders.

What is Bicarbonate?

Bicarbonate (HCO₃⁻) is a negatively charged ion (anion) that acts as a buffer in the body’s extracellular fluid. It helps maintain the pH of the blood within a very narrow range, typically 7.35 to 7.45, which is critical for normal cellular function.

This buffering capacity is primarily achieved through the bicarbonate-carbonic acid buffer system, a chemical equilibrium that can neutralize excess acids or bases in the blood.

The key chemical equation is:

CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻

This reaction demonstrates the close relationship between carbon dioxide (CO₂), water (H₂O), carbonic acid (H₂CO₃), hydrogen ions (H⁺), and bicarbonate (HCO₃⁻). The lungs help regulate this balance by controlling the level of CO₂, while the kidneys maintain stability by managing bicarbonate concentrations.

Bicarbonate’s Role in Respiratory Care

For respiratory therapists, bicarbonate is a cornerstone of acid-base analysis. It is one of the three main components assessed in arterial blood gas interpretation, alongside partial pressures of oxygen (PaO₂) and carbon dioxide (PaCO₂). Together, these values help determine if a patient has a respiratory or metabolic disturbance.

1. Buffering Respiratory Acidosis or Alkalosis

When CO₂ builds up due to hypoventilation, it leads to respiratory acidosis. The kidneys compensate by retaining bicarbonate to neutralize the excess hydrogen ions. In contrast, hyperventilation causes respiratory alkalosis, and the kidneys respond by excreting more bicarbonate.

2. Indicating Metabolic Imbalances

Low bicarbonate levels can suggest metabolic acidosis (e.g., from diabetic ketoacidosis or renal failure), while high levels can indicate metabolic alkalosis (e.g., from excessive vomiting or diuretic use). In either case, respiratory compensation may be involved, and a respiratory therapist must recognize these shifts to tailor ventilatory support accordingly.

3. Guiding Ventilator Management

In mechanically ventilated patients, bicarbonate levels are used to guide settings that influence ventilation and CO₂ removal. For example, if a patient has chronic CO₂ retention (e.g., in COPD), an elevated bicarbonate level indicates renal compensation. Sudden changes in pH without a corresponding change in bicarbonate could signify an acute respiratory imbalance, requiring ventilator adjustments.

Clinical Examples

• Chronic COPD: These patients often have elevated PaCO₂ levels due to poor ventilation. Over time, the kidneys compensate by increasing bicarbonate to maintain pH. A “normal” pH with elevated PaCO₂ and HCO₃⁻ suggests chronic compensation.
• Diabetic Ketoacidosis (DKA): Patients present with metabolic acidosis and low bicarbonate levels. The respiratory system compensates with Kussmaul breathing (deep, rapid breaths) to blow off CO₂ and raise pH.
• Ventilator Weaning: An understanding of bicarbonate levels is essential during the weaning process. If a patient has compensated respiratory acidosis (elevated HCO₃⁻), sudden changes in CO₂ levels during weaning can destabilize their pH balance.

Interpreting HCO₃⁻ in ABG Analysis

In ABG results, bicarbonate is typically reported in milliequivalents per liter (mEq/L), with a normal range of 22–26 mEq/L.

• < 22 mEq/L: Suggests metabolic acidosis
• > 26 mEq/L: Suggests metabolic alkalosis

Note: Always consider the pH and PaCO₂ in conjunction with HCO₃⁻ to determine the primary disorder and the presence of compensation.

Bicarbonate Practice Questions

1. What is bicarbonate (HCO₃⁻) and why is it important in the body?  
It is an extracellular anion that acts as the principal buffer of extracellular fluid (ECF) and blood, helping regulate pH.

2. How does the respiratory system influence bicarbonate balance?  
By regulating carbon dioxide levels through exhalation, since CO₂ and HCO₃⁻ are linked via the carbonic acid equation catalyzed by carbonic anhydrase.

3. How is hydrogen ion (H⁺) introduced into the body?  
Through metabolic processes and dietary intake.

4. How is bicarbonate lost from the body daily?  
It is lost in small amounts through feces and regulated by renal mechanisms.

5. What is the normal range for body pH?  
The normal pH of the body is between 7.35 and 7.45.

6. How does the body compensate to maintain normal pH when PaCO₂ increases?  
Bicarbonate levels also increase to buffer the excess acid, maintaining pH through a mirror response.

7. How do the kidneys regulate bicarbonate levels?  
By filtering, reabsorbing, and regenerating bicarbonate through acid excretion mechanisms.

8. What percentage of bicarbonate reabsorption occurs in the proximal tubule?  
Approximately 85–90% of filtered bicarbonate is reabsorbed in the proximal convoluted tubule.

9. What happens to bicarbonate in the distal tubule and collecting duct?  
The remaining 10–15% is reabsorbed or regenerated as needed, especially during acidaemia.

10. How much plasma is filtered daily through the glomerulus, and what is the typical plasma bicarbonate level?  
Around 180 L/day of filtrate is processed, with a normal plasma bicarbonate level of 24 mmol/L.

11. Why must filtered bicarbonate be reabsorbed?  
To prevent excessive loss of bicarbonate and maintain acid-base balance in the body.

12. What enzyme accelerates bicarbonate reabsorption in the proximal tubule?  
Carbonic anhydrase, located on the brush border of tubular cells.

13. How is CO₂ involved in proximal bicarbonate reabsorption?  
CO₂ diffuses freely into tubular cells, combines with water to form H₂CO₃, which dissociates into H⁺ and HCO₃⁻.

14. What drives H⁺ ion secretion into the tubule during bicarbonate reabsorption?  
Secondary active transport using the sodium gradient established by Na⁺ reabsorption.

15. What occurs on the basal side of tubular cells during bicarbonate reabsorption?  
Sodium is actively transported out, facilitating continued Na⁺/H⁺ exchange on the luminal side.

16. How does chloride play a role in distal bicarbonate reabsorption?  
Chloride is exchanged for bicarbonate to maintain electrical neutrality in the cell.

17. What triggers increased bicarbonate reabsorption in the collecting tubule?  
States of acidaemia, where maintaining blood pH becomes critical.

18. How is bicarbonate regenerated by the kidneys?  
Through titratable acid excretion and ammonium excretion processes.

19. Why is bicarbonate regeneration necessary?  
Because protons from metabolism consume bicarbonate; regeneration restores buffering capacity.

20. What is titratable acid excretion?  
It’s the renal excretion of H⁺ ions buffered by non-bicarbonate buffers like phosphate and creatinine.

21. Which urinary buffers are involved in titratable acid secretion?  
Phosphate, urate, creatinine, and beta-hydroxybutyrate.

22. Where in the nephron does titratable acid excretion mainly occur?  
In the distal tubule segments.

23. What drives H⁺ secretion in titratable acid excretion?  
A steep sodium gradient that fuels H⁺ transport into the tubule lumen.

24. What dietary sources influence phosphate levels and acid buffering?  
Phosphate-rich foods like processed meats, game, and smoked salmon.

25. How does the body respond to acidemia through ammonium excretion?  
By increasing ammonium production from amino acid metabolism, especially from glutamine.

26. Which organs contribute to ammonium production during acidaemia?  
The muscles, gut, and liver.

27. What is the role of glutamine in ammonium excretion?  
It increases renal uptake and metabolism to produce ammonia for buffering excess H⁺.

28. How does the body regulate bicarbonate regeneration in response to acid-base changes?  
Titratable acid excretion remains relatively constant, but ammonium excretion can increase significantly to meet buffering needs.

29. What role does the kidney play in primary respiratory disorders?  
It provides compensation by adjusting bicarbonate reabsorption and regeneration to help stabilize blood pH.

30. What happens in respiratory acidaemia?  
A rise in PaCO₂ causes intracellular acidaemia, stimulating glutamine uptake, increasing ammonium excretion, and enhancing bicarbonate regeneration and reabsorption.

31. How does intracellular pH affect bicarbonate handling during respiratory acidosis?  
A low intracellular pH boosts proton secretion and maximizes bicarbonate reabsorption in renal tubules.

32. What changes occur during respiratory alkalaemia?  
Decreased PaCO₂ raises intracellular pH, which reduces proton secretion and leads to decreased bicarbonate reabsorption, increasing bicarbonate loss in urine.

33. What is a common cause of respiratory alkalaemia?  
High altitude, which reduces PaCO₂ and triggers compensatory renal bicarbonate excretion.

34. How does a drop in extracellular fluid (ECF) volume or an increase in angiotensin II affect bicarbonate?  
It stimulates sodium and bicarbonate reabsorption and promotes H⁺ secretion, increasing bicarbonate regeneration.

35. What mechanism is enhanced when the body is fluid-depleted?  
The Na⁺/H⁺ exchange in the renal tubule is stimulated to promote sodium and bicarbonate retention.

36. What happens to bicarbonate handling when the tubular lumen has excess H⁺?  
All filtered bicarbonate is reabsorbed, and additional new bicarbonate is generated.

37. What are the major factors regulating renal bicarbonate handling?  
Changes in PCO₂, H⁺ concentration, ECF volume, angiotensin, aldosterone, and potassium levels.

38. How does impaired kidney function affect acid-base balance?  
It leads to metabolic acidaemia due to decreased ammonium excretion and reduced bicarbonate regeneration.

39. What happens when glomerular filtration rate (GFR) falls below 40 mL/min?  
The kidney cannot regenerate enough ammonia, resulting in progressive metabolic acidosis.

40. What is renal tubular acidosis (RTA) type 1?  
A distal tubular defect causing poor H⁺ secretion, urine pH around 5.5, low plasma K⁺, and plasma bicarbonate under 10 mmol/L, despite normal GFR.

41. What population is most affected by RTA type 1?  
It is less common overall but can occur in chronic kidney disease patients, especially those with diabetes or hypertension.

42. What is renal tubular acidosis (RTA) type 2?  
A proximal defect impairing bicarbonate reabsorption, with low plasma K⁺, plasma bicarbonate between 10–20 mmol/L, and typically variable urine pH.

43. What substances are known to cause RTA type 2?  
ACE inhibitors, aminoglycosides, contrast media, NSAIDs, and proton pump inhibitors.

44. Who is most likely to develop RTA type 2?  
It is most commonly observed in pediatric populations.

45. What is renal tubular acidosis (RTA) type 4?  
A form of hyperkalemic RTA caused by reduced aldosterone levels, leading to impaired NH₄⁺ production, low urine pH, high plasma K⁺, and plasma bicarbonate between 15–20 mmol/L.

46. What is the most common type of RTA in adults?  
Type 4 RTA, associated with aldosterone deficiency and hyperkalemia.

47. What is the chemical equation for the bicarbonate buffering system?  
CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻

48. What happens when carbon dioxide dissolves in blood?  
It reacts with water to form carbonic acid (H₂CO₃), a key step in buffering blood pH.

49. How does carbonic acid help maintain pH balance?  
It dissociates into H⁺ and HCO₃⁻, allowing hydrogen ions to be buffered and preventing sharp drops in pH.

50. What happens when blood becomes too acidic (low pH)?  
Bicarbonate ions (HCO₃⁻) bind to hydrogen ions (H⁺), forming carbonic acid (H₂CO₃) and reducing blood acidity.

51. How does the bicarbonate buffer system respond when blood becomes too basic (high pH)?  
Carbonic acid (H₂CO₃) dissociates into hydrogen ions (H⁺) and bicarbonate, increasing blood acidity.

52. What is the normal physiological pH range of human blood maintained by the bicarbonate buffer system?  
7.35 to 7.45

53. Which enzyme catalyzes the reversible reaction between CO₂ and H₂O to form carbonic acid in the bicarbonate buffer system?  
Carbonic anhydrase

54. Where in the cell is the buffering reaction between carbonic acid and bicarbonate primarily regulated?  
In the cytoplasm

55. Where in the body does carbon dioxide primarily exit the blood to be exhaled?  
At the alveoli of the lungs

56. What is formed when bicarbonate (HCO₃⁻) binds with a hydrogen ion (H⁺)?  
Carbonic acid (H₂CO₃)

57. According to Le Chatelier’s Principle, how does an increase in CO₂ affect blood pH?  
It shifts the equilibrium toward more hydrogen ion production, lowering the pH.

58. How does the respiratory system respond to elevated CO₂ levels and increasing acidity in the blood?  
It increases the breathing rate to eliminate more CO₂.

59. Which ion do renal tubule cells secrete into the urine to reduce blood acidity?  
Hydrogen ions (H⁺)

60. What enzyme in the proximal tubule allows carbonic acid to be converted back into CO₂ and H₂O for bicarbonate reabsorption?  
Carbonic anhydrase

61. How do the kidneys compensate for metabolic alkalosis (elevated blood pH)?  
By excreting more bicarbonate (HCO₃⁻)

62. What is the typical bicarbonate-to-carbonic acid ratio needed to maintain normal blood pH?  
20:1

63. How does the bicarbonate buffer system respond during respiratory acidosis with elevated CO₂?
It binds excess hydrogen ions with bicarbonate to stabilize pH.

64. What term describes the deep, rapid breathing pattern seen during metabolic acidosis as the body attempts to blow off CO₂?  
Kussmaul respiration

65. What are the primary roles of bicarbonate anions in the body?  
They maintain acid-base balance and bind with metabolic acids and chloride ions.

66. What are the four major buffer systems that help regulate body pH?  
Sodium bicarbonate–carbonic acid, phosphate, hemoglobin, and protein buffer systems.

67. Which buffer system is the major extracellular fluid (ECF) buffer and used to assess acid-base balance?  
The sodium bicarbonate–carbonic acid buffer system

68. How is carbonic acid (H₂CO₃) formed in the body?  
By the combination of carbon dioxide (CO₂) and water (H₂O)

69. How does CO₂ produced from metabolism contribute to acid-base balance?  
It diffuses into the blood, mixes with water, and forms carbonic acid.

70. Which enzyme facilitates the dissociation of carbonic acid into H⁺ and HCO₃⁻ in body fluids?  
Carbonic anhydrase

71. In which two organs is carbonic anhydrase most active in regulating acid-base balance?  
The lungs and kidneys

72. What compound is formed when carbon dioxide (CO₂) combines with water (H₂O)?  
Carbonic acid (H₂CO₃)

73. What are the two products formed when carbonic acid dissociates with the help of carbonic anhydrase?  
Hydrogen ions (H⁺) and bicarbonate ions (HCO₃⁻)

74. To maintain a normal blood pH of 7.40, what is the required ratio of bicarbonate to carbonic acid?  
20:1, with 20 parts bicarbonate to 1 part carbonic acid

75. How do the kidneys compensate during respiratory acidosis?  
By excreting more hydrogen ions and reabsorbing more bicarbonate

76. What are common causes of metabolic acidosis?  
Shock, diabetic ketoacidosis, renal failure, and diarrhea

77. What is a key effect of metabolic acidosis on serum chemistry?  
Decreased serum bicarbonate levels

78. How do the kidneys compensate for metabolic acidosis?  
By excreting more acid and increasing bicarbonate reabsorption

79. How do the lungs compensate during metabolic acidosis?  
By increasing the respiratory rate and depth (Kussmaul respirations)

80. What are common causes of respiratory alkalosis?  
Hyperventilation due to anxiety or aspirin overdose

81. What is a common effect of respiratory alkalosis on arterial blood gases?  
Decreased partial pressure of carbon dioxide (PaCO₂)

82. How do the kidneys compensate for respiratory alkalosis?  
By excreting fewer hydrogen ions and reabsorbing less bicarbonate

83. What are common causes of metabolic alkalosis?  
Vomiting and excessive intake of antacids

84. What is a typical effect of metabolic alkalosis on serum chemistry?  
Increased serum bicarbonate levels

85. How do the kidneys compensate during metabolic alkalosis?  
By excreting less acid and reducing bicarbonate reabsorption

86. What is the defining characteristic of respiratory acidosis?  
An increase in arterial carbon dioxide (PaCO₂)

87. What is the defining characteristic of metabolic acidosis?  
A decrease in serum bicarbonate levels

88. What is the defining characteristic of metabolic alkalosis?  
An increase in serum bicarbonate levels

89. What is the defining characteristic of respiratory alkalosis?  
A decrease in arterial carbon dioxide (PaCO₂)

90. What buffer system is primarily responsible for maintaining the pH of extracellular fluid (ECF)?  
The bicarbonate–carbonic acid buffer system

91. What is the main role of bicarbonate ions in the blood?  
To buffer excess hydrogen ions and maintain acid-base balance

92. How does hypoventilation affect blood pH through the bicarbonate buffer system?  
It causes CO₂ retention, leading to respiratory acidosis.

93. During respiratory alkalosis, what happens to bicarbonate levels as a compensatory mechanism?  
Bicarbonate is excreted by the kidneys to lower pH

94. Why is bicarbonate considered an “alkaline reserve”?  
Because it neutralizes acids by binding with hydrogen ions

95. What does a low bicarbonate level on an ABG typically indicate?  
Metabolic acidosis

96. What does a high bicarbonate level on an ABG suggest?  
Metabolic alkalosis

97. How does bicarbonate help maintain a stable blood pH despite fluctuations in CO₂?  
By buffering the hydrogen ions generated from carbonic acid dissociation

98. Which organ system is primarily responsible for the reabsorption and regeneration of bicarbonate?  
The renal system (kidneys)

99. In what part of the nephron does most bicarbonate reabsorption occur?  
The proximal convoluted tubule

100. How does bicarbonate reabsorption help regulate systemic pH in the kidneys?  
By conserving bicarbonate and excreting hydrogen ions in response to acidosis

Final Thoughts

Bicarbonate (HCO₃⁻) may seem like a small component in the broader scope of respiratory care, but its importance is profound. It serves as a biochemical marker for identifying and differentiating between respiratory and metabolic imbalances.

For respiratory therapists, mastering bicarbonate interpretation is essential for ABG analysis, ventilator management, and overall patient care. By understanding how HCO₃⁻ interacts with CO₂ and pH, clinicians can make informed decisions that improve patient outcomes and enhance respiratory function.