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Pathophysiology · Chapter 13. Acid-Base Disorders

Blood buffer systems

Chemical buffer systems are the body's first mobile and efficient line of defense against acid-base balance (ABB) shifts. They transform strong acids and bases into weak ones, reacting in just 10–40 seconds and preventing critical pH changes.

Reaction speedThey start working instantly, eliminating moderate ABB shifts in just 10–40 seconds.
Blood capacityErythrocytes account for 57% of the total buffer capacity, and plasma accounts for the remaining 43%.
Acid loadNormally, the body produces almost 20 times more acidic products than alkaline ones.
Bone reserveIn acute pathologies, bones release carbonates, providing 30–40% of the buffer capacity.
5 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

Why buffers are needed and how they work

During normal vital activity, our body continuously generates a colossal amount of metabolites. The physiological norm is such that acidic products are formed almost 20 times more than basic (alkaline) ones. The consequence of this imbalance is the dominance in the body of systems that ensure rapid neutralization, secretion, and excretion of excess acids.

The first line of defense is chemical buffer systems. These are mobile complexes that are activated immediately when the concentration of hydrogen ions changes. Their main principle of action is the transformation of strong acids and bases into weak ones. Due to a certain capacity and high efficiency, they are able to smooth out moderate fluctuations in the acid-base state in just a few dozen seconds.

Main chemical buffers

The total buffer capacity of blood is distributed unevenly: 57% is provided by erythrocytes and 43% by plasma. There are four main chemical systems:

  1. Hemoglobin. The largest capacity buffer, accounting for more than 50% of the total blood buffer capacity. It functions exclusively inside erythrocytes. Oxygenated hemoglobin (HbO_2) acts as the acidic component—it dissociates about 80 times stronger than reduced hemoglobin (Hb), releasing hydrogen ions into the medium and binding cations (mainly potassium). Reduced hemoglobin works as the main component. The main task of the system is participation in the transport of carbon dioxide from tissues to the lungs.
  2. Bicarbonate. A key buffer of blood and extracellular fluid. In the extracellular environment, it consists of a mixture of carbonic acid and sodium bicarbonate, and inside cells, sodium salts are replaced by potassium and magnesium salts. This is an open system, closely associated with the function of external respiration and the kidneys.
  3. Protein. The main intracellular buffer, providing about 3/4 of the intracellular fluid capacity. It consists of a weakly dissociating protein with acidic properties and a salt of a strong base. In acidosis, the accumulating excess of acids interacts with the protein salt, resulting in the formation of a neutral salt and a weak acid.
  4. Phosphate. Accounts for about 8% of the total capacity. In the blood itself, its role is small, but it plays a significant role inside cells and in the renal tubules due to the high concentration of phosphates. The alkaline component is sodium hydrogen phosphate (Na_2HPO_4), and the acidic component is sodium dihydrogen phosphate (NaH_2PO_4).
Buffer systemBlood plasma (%)Erythrocytes (%)
Bicarbonate3518
Hemoglobin—35
Protein7—
Phosphate14
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Physiological compensation and ABB disorders

If chemical buffers cannot cope with the load, physiological (organ) regulatory mechanisms are activated. The lungs, kidneys, liver, and gastrointestinal tract participate in them. Unlike chemical reactions, organ compensation requires significantly more time to achieve an effect—from several minutes to several hours.

In various pathologies, specific primary ABB shifts occur, which the body compensates for with counter-reactions:

  • Respiratory acidosis. Primarily, pH decreases and the carbon dioxide tension (pCO_2) increases. For compensation, the kidneys begin to actively retain bicarbonate (HCO_3^-).
  • Respiratory alkalosis. Primarily, pH increases and pCO_2 drops. The kidneys react by increased excretion of bicarbonate from the body.
  • Non-respiratory (metabolic) acidosis. Characterized by a drop in pH and a decrease in bicarbonate levels. Pulmonary hyperventilation is activated to flush out excess carbon dioxide (decrease in pCO_2).
  • Non-respiratory (metabolic) alkalosis. Against the background of rising pH and bicarbonate, the lungs reduce ventilation (hypoventilation) to accumulate carbon dioxide.

In critical situations (acute heart, respiratory or renal failure, shock, coma), bones come to the rescue. They function as a huge depot for buffer systems, containing a large amount of carbonic acid salts (calcium, sodium, and potassium carbonates). With an acute increase in acid content, bone tissue is able to provide 30–40% of the body's entire buffer capacity.

Briefly: answers to topical questions

What are the normal arterial and venous blood pH values?

Normal blood pH values are 7.35 for venous blood and 7.45 for arterial blood. This parameter refers to strict physiological constants that are maintained in the body with practically no variability. Maintaining the acid-base state at a given level is ensured by several mechanisms: chemical buffer systems, respiration by removing carbon dioxide, and kidneys by regulating bicarbonate reabsorption and hydrogen ion secretion. Any shift in pH beyond these reference values indicates pathology and leads to the development of acidosis or alkalosis.

By what biochemical mechanism does bicarbonate reabsorption occur in the renal tubules?

Bicarbonate reabsorption in the renal tubules is carried out by the mechanism of electrostatic attraction to sodium and potassium ions. This process is inextricably linked with enzymatic activity in epithelial cells, where the enzyme carbonic anhydrase breaks down carbonic acid. The reabsorption of bicarbonate ions back into the blood is critically important for maintaining its alkaline reaction. In parallel with this, hydrogen ions are secreted into the tubule lumen, which enter into a buffer reaction with the filtered sodium hydrogen phosphate, ensuring the excretion of acids.

Which buffer systems form the basis of the intracellular fluid?

The basis of the intracellular fluid is formed by three main types of buffer systems:

  • Protein system — is the main intracellular buffer, providing approximately 3/4 of the intracellular fluid capacity. It includes a weakly dissociating protein with acidic properties.
  • Phosphate system — plays a significant role in regulating the acid-base state inside cells due to the high concentration of phosphates compared to the extracellular environment.
  • Carbonate system (bicarbonate) — inside cells, potassium and magnesium salts are included in this system instead of sodium salts.
How to memorize

How to easily remember ABB compensation: "Whosoever is to blame does not fix it." In respiratory (pulmonary) shifts, the kidneys take over compensation (change the bicarbonate level), and in metabolic (non-respiratory) disorders, the lungs come to the rescue (change ventilation).

Class and exam questions

Which blood buffer is the most powerful?

Hemoglobin buffer. It accounts for more than 50% of the total blood buffering capacity, while operating exclusively inside erythrocytes.

Why is the bicarbonate system called open?

Because its components are constantly regulated by external organs: the lungs control the level of carbon dioxide, and the kidneys maintain the necessary bicarbonate anion content.

What role do bones play in pH regulation?

Bone tissue serves as a reserve depot of carbonic acid salts. In acute conditions (shock, coma, organ failure), bones release carbonates, providing up to 30–40% of the buffer capacity.

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What else to study on this topic

  • Mechanisms of protein buffer action in alkalosis
  • The role of the liver and gastrointestinal tract in the physiological regulation of ABB
  • Features of the phosphate buffer in the renal tubules
  • Differences between intracellular and extracellular bicarbonate buffers
  • Carbon dioxide transport by the hemoglobin system

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