- The most crucial buffer system in maintaining acid-base balance in human blood is the Bicarbonate buffer system (HCO₃⁻ / H₂CO₃).
- This system plays a vital role because it is the most efficient in neutralizing strong acids and bases in the blood, thus helping to maintain a stable pH close to the normal range of 7.35-7.45.

- The bicarbonate buffer system works by balancing the concentration of carbonic acid (H₂CO₃) and bicarbonate ions (HCO₃⁻).
- When an acid is introduced to the blood, bicarbonate ions react with the hydrogen ions (H⁺) to form carbonic acid, which then dissociates into water and carbon dioxide.

- This process is dynamic and reversible, allowing the respiratory system to regulate blood pH by adjusting the levels of CO₂ through breathing.
- The kidneys also contribute by excreting or reabsorbing bicarbonate to maintain the acid-base balance.

- While other buffer systems such as the Phosphate buffer system (HPO₄²⁻ / H₂PO₄⁻), Protein buffer system (Hemoglobin and plasma proteins), and Ammonia buffer system (NH₃ / NH₄⁺) play secondary or localized roles, they are not as significant in the overall blood pH regulation as the bicarbonate system.

- In summary, the bicarbonate buffer system is essential because of its high buffering capacity, interaction with respiratory and renal systems, and its ability to effectively maintain the physiological pH of blood.

Reference: Guyton and Hall Textbook of Medical Physiology, 13th Edition, Chapter 26/Pages 333-337