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Physiology · Blood

Blood buffer systems

Blood buffer systems are first-line physicochemical mechanisms of defense that instantly respond to shifts in acid-base balance. They bind or release hydrogen and hydroxyl ions, preventing sharp pH changes when acids or bases enter the bloodstream.

The most powerful.The hemoglobin system provides 75% of the blood's buffer capacity
An open system.The bicarbonate buffer dumps excess CO2 through the lungs
Universal composition.Each system consists of a weak acid and a conjugate base
Extracellular environment.Bicarbonates provide up to 98% of plasma and CSF capacity
4 min readFor medical studentsUpdated 09/24/2026
Material prepared by WhiteCoat Pro editorial team based on platform study guidesReviewed by medical editor: Aulov A. A., general practitioner · 09/24/2026

General principle of buffer function

Maintaining homeostasis of the internal environment requires immediate reactions. Buffer systems act as chemical "shock absorbers." Structurally, each such buffer is formed by a weak acid and a conjugate base, which are present in a strictly defined ratio.

When a small amount of an extraneous acid or base is added to a solution, the buffer system reacts with it. $H^+$ or $OH^-$ ions are bound by the buffer components, turning into weakly dissociating compounds or water. Thus, free aggressive ions disappear, and the pH level remains stable.

Bicarbonate buffer system

This buffer consists of weak carbonic acid ($H_2CO_3$) and the bicarbonate ion ($HCO_3^-$) in a 1:20 ratio (acid to ion).

The mechanism of action depends on the nature of the shift:

  • In acidosis (acidification): excess $H^+$ ions bind to the base ($HCO_3^-$). Carbonic acid ($H_2CO_3$) is formed. Then, under the action of the enzyme carbonic anhydrase, it breaks down into water and carbon dioxide. Since excess $CO_2$ is continuously removed by the lungs, the bicarbonate system is called an "open" system.
  • In alkalosis (alkalinization): $OH^-$ ions interact with hydrogen ions that are part of carbonic acid to form water molecules ($H_2O$).

Despite the fact that this buffer accounts for only 7–9% of the total buffer capacity of whole blood, it is critically important for extracellular fluids. In plasma, lymph, and cerebrospinal fluid, its share makes up an impressive 97–98% of the total buffer capacity.

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Phosphate and protein systems

The other two systems play a secondary but important role in various fluid compartments.

The phosphate buffer consists of the dihydrogen phosphate ion ($H_2PO_4^-$) and the monohydrogen phosphate ion ($HPO_4^{2-}$). Their normal ratio is 1:4. The main task of this system in the blood is to maintain the optimal balance of bicarbonate buffer components. This is described by the reaction equation: $H_2CO_3 + HPO_4^{2-} \leftrightarrow H_2PO_4^- + HCO_3^-$

The protein buffer system operates due to the amphoteric nature of proteins. Depending on the environment, proteins behave differently:

  • In a basic environment, they dissociate to form $H^+$ ions, meaning they act as acids.
  • In an acidic environment, they release $OH^-$ ions.

When $H^+$ concentration increases, proteins form weakly dissociating acids, and with an excess of $OH^-$, they promote the formation of water. The capacity of plasma proteins is quite modest—only about 2% of the extracellular fluid's buffer capacity.

Hemoglobin buffer system

This is the most powerful buffer system, accounting for 75% (3/4) of the total blood buffer capacity. Its incredible efficiency is due to two factors: the amphoteric properties of the protein moiety (globin) and the effect of oxygenation on the acid-base characteristics of hemoglobin.

Key properties of different forms of hemoglobin:

  1. Deoxygenated hemoglobin ($Hb$) is a stronger base, so it binds free hydrogen ions ($H^+$) much more easily.
  2. Oxyhemoglobin ($HbO_2$) behaves as a stronger acid compared to the deoxygenated form.

Physiological mechanism in tissues: When blood passes through tissue capillaries, it releases oxygen and picks up carbon dioxide. Oxyhemoglobin turns into deoxygenated hemoglobin. The carbon dioxide entering the erythrocyte (acting as an acidic component) is almost completely and instantly neutralized, as the resulting deoxygenated hemoglobin acts as a strong base and takes the brunt of the load.

Briefly: answers to topical questions

What parameters are used to assess the acid-base state of blood in clinical practice (Astrup method)?

The assessment of acid-base status and its shifts in clinical practice is carried out taking into account the normal range of the following parameters:

  • pH.
  • pCO2.
  • SB (Standard Bicarbonate) — standard bicarbonate of blood plasma.
  • BB (Buffer Base) — buffer bases of capillary blood.
  • BE (Base Excess) — base excess of capillary blood.

What is the role of the kidneys in regulating the body's acid-base balance?

The kidneys regulate the acid-base balance through processes in the renal tubules.

Main processes of renal regulation:

  • Reabsorption — the uptake of bicarbonate and other metabolites back from the primary urine.
  • Secretion — the release of hydrogen ions into the tubular lumen in exchange for reabsorbed sodium ions.

Main mechanisms for reducing or eliminating acid-base shifts in the nephrons:

  • Acidogenesis.
  • Ammoniogenesis.
  • Phosphate secretion.
  • K+, Na+ exchange mechanism.
How to memorize

For memorizing capacities: Hemoglobin is the Main one in blood (75%), Bicarbonate is the Main one extracellularly (98% of plasma).

Class and exam questions

Because one of the final products of its reaction—carbon dioxide ($CO_2$)—does not accumulate, but is continuously removed from the body via the respiratory system (lungs).

Because one of the final products of its reaction—carbon dioxide ($CO_2$)—does not accumulate, but is continuously removed from the body via the respiratory system (lungs).

Due to the amphoteric nature of proteins: in an acidic environment they can release hydroxyl ions, and in an alkaline environment they dissociate as acids, giving off hydrogen ions.

Due to the amphoteric nature of proteins: in an acidic environment they can release hydroxyl ions, and in an alkaline environment they dissociate as acids, giving off hydrogen ions.

In tissues, hemoglobin releases oxygen and converts to the deoxygenated form ($Hb$). This form is a strong base and easily binds hydrogen ions from the incoming carbon dioxide, preventing a drop in pH.

In tissues, hemoglobin releases oxygen and converts to the deoxygenated form ($Hb$). This form is a strong base and easily binds hydrogen ions from the incoming carbon dioxide, preventing a drop in pH.

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What else to study on this topic

  • The role of the enzyme carbonic anhydrase in erythrocytes
  • Mechanisms of tissue acidosis development
  • The relationship between gas exchange and acid-base balance
  • Differences in buffer capacity between intracellular and extracellular fluid

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