Disorders of acid-base state

One of the main constants of the body is the constancy of the concentration of hydrogen ions (H ⁺ ) in the extracellular fluid, which in healthy individuals is 40±5 nmol/l. For convenience, the concentration of H ⁺ is most often expressed as a negative logarithm (pH). Normally, the pH value of the extracellular fluid is 7.4. pH regulation is necessary for the normal functioning of the body's cells.

The acid-base balance of the body includes three main mechanisms:

• functioning of extra- and intracellular buffer systems;
• respiratory regulation mechanisms;
• renal mechanism.

Acid-base imbalances are pathological reactions that are associated with acid-base imbalances. Acidosis and alkalosis are distinguished.

Buffer systems of the body

Buffer systems are organic and inorganic substances that prevent a sharp change in the concentration of H ⁺ and, accordingly, the pH value when adding acid or alkali. These include proteins, phosphates and bicarbonates. These systems are both inside and outside the cells of the body. The main intracellular buffer systems are proteins, inorganic and organic phosphates. Intracellular buffers compensate for almost the entire load of carbonic acid (H ₂ CO ₃ ), more than 50% of the load of other inorganic acids (phosphoric, hydrochloric, sulfuric, etc.). The main extracellular buffer of the body is bicarbonate.

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Respiratory mechanisms of pH regulation

They depend on the work of the lungs, which are able to maintain the partial pressure of carbon dioxide (CO2 ₎ in the blood at the required level, despite large fluctuations in the formation of carbonic acid. Regulation of CO2 release _occurs due to changes in the rate and volume of pulmonary ventilation. An increase in the minute volume of respiration leads to a decrease in the partial pressure of carbon dioxide in arterial blood and vice versa. The lungs are considered the first line in maintaining the acid-base balance, since they provide a mechanism for immediate regulation of CO2 _release.

Renal mechanisms of acid-base balance maintenance

The kidneys are involved in maintaining the acid-base balance, excreting excess acids in the urine and preserving bases for the body. This is achieved through a number of mechanisms, the main ones being:

• reabsorption of bicarbonates by the kidneys;
• formation of titratable acids;
• formation of ammonia in renal tubular cells.

Bicarbonate reabsorption by the kidneys

In the proximal tubules of the kidneys, almost 90% of HCO3 is absorbed not through direct transport of HCO3 through the membrane, but through complex exchange mechanisms, the most important of which is considered to be the secretion of H ⁺ into the lumen of the nephron.

In the cells of the proximal tubules, unstable carbonic acid is formed from water and carbon dioxide under the influence of the enzyme carbonic anhydrase, which quickly decomposes into H ⁺ and HCO ₃ ". The hydrogen ions formed in the tubular cells enter the luminal membrane of the tubules, where they are exchanged for Na ⁺, as a result of which H ⁺ enters the lumen of the tubules, and the sodium cation enters the cell and then into the blood. The exchange occurs with the help of a special carrier protein - Na ⁺ -H ^{+ -exchanger. The entry of hydrogen ions into the lumen of the nephron activates the reabsorption of HCO}₃ ~ into the blood. At the same time, in the lumen of the tubule, the hydrogen ion quickly combines with constantly filtered HCO ₃ to form carbonic acid. With the participation of carbonic anhydrase, acting on the luminal side of the brush border, H2C0 ₃ is converted into H2O _and CO _2. In this case, carbon dioxide diffuses back into the cells of the proximal tubules, where it combines with H2O _to form carbonic acid, thus completing the cycle.

Thus, the secretion of H ⁺ ion ensures the reabsorption of bicarbonate in an equivalent amount of sodium.

In the loop of Henle, approximately 5% of the filtered bicarbonate is reabsorbed, and in the collecting tube, another 5%, also due to the active secretion of H ⁺.

Formation of titratable acids

Some weak acids present in plasma are filtered and serve as buffer systems in urine. Their buffer capacity is called "titratable acidity". The main component of these urine buffers is HPO4 _{~, which after the addition of a hydrogen ion is converted into a}^{disubstituted} phosphoric acid ion (HPO42 ₊ H ⁺ = H2PO _~ ), which has a lower acidity.

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Formation of ammonia in renal tubular cells

Ammonia is formed in the cells of the renal tubules during the metabolism of keto acids, especially glutamine.

At neutral and especially at low pH values of the tubular fluid, ammonia diffuses from the tubular cells into its lumen, where it combines with H ⁺ to form an ammonium anion (NH ₃ + H ⁺ = NH ₄⁺ ). In the ascending limb of the loop of Henle, NH ₄⁺ cations are reabsorbed, which accumulate in the renal medulla. A small amount of ammonium anions dissociate into NH and hydrogen ions, which are reabsorbed. NH ₃ can diffuse into the collecting ducts, where it serves as a buffer for the H ⁺ secreted by this part of the nephron.

The ability to increase the formation of NH ₃ and the excretion of NH ₄⁺ is considered the main adaptive reaction of the kidneys to an increase in acidity, which allows the excretion of hydrogen ions by the kidneys.

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Acid-base imbalances

In various clinical conditions, the concentration of hydrogen ions in the blood may deviate from the norm. There are two main pathological reactions associated with a violation of the acid-base balance - acidosis and alkalosis.

Acidosis is characterized by low blood pH (high H ⁺ concentration ) and low blood bicarbonate concentration;

Alkalosis is characterized by a high blood pH (low H ⁺ concentration ) and a high blood bicarbonate concentration.

There are simple and mixed variants of acid-base imbalance. In primary, or simple, forms, only one imbalance is observed.

Simple variants of acid-base imbalance

• Primary respiratory acidosis. Associated with an increase in p _a CO ₂.
• Primary respiratory alkalosis. Occurs as a result of a decrease
• Metabolic acidosis. Caused by a decrease in the concentration of HCO3 _~.
• Metabolic alkalosis. Occurs when the concentration of HCO3 _increases.

Quite often, the above-mentioned disorders may be combined in a patient, and they are designated as mixed. In this textbook, we will focus on simple metabolic forms of these disorders.