Introduction
Buffer systems of the body
An organism can be defined as a physicochemical system that exists in the environment in a stationary state. It is this ability of living systems to maintain a stationary state in a constantly changing environment that determines their survival. To ensure a stationary state, all organisms - from the morphologically simplest to the most complex - have developed a variety of anatomical, physiological and behavioral adaptations that serve one purpose - maintaining the constancy of the internal environment.
This relative dynamic constancy of the internal environment (blood, lymph, tissue fluid) and the stability of the basic physiological functions (blood circulation, respiration, thermoregulation, metabolism, etc.) of the human and animal body is called homeostasis.
This process is carried out primarily by the activity of the lungs and kidneys due to the respiratory and excretory functions. Homeostasis is based on maintaining the acid-base balance.
The main function of buffer systems is to prevent significant pH shifts by reacting the buffer with both an acid and a base. The action of buffer systems in the body is aimed primarily at neutralizing the resulting acids.
H+ + buffer-<==>H-buffer
There are several different buffer systems in the body at the same time. In functional terms, they can be divided into bicarbonate and non-bicarbonate. The non-bicarbonate buffer system includes hemoglobin, various proteins and phosphates. It is most active in the blood and inside cells.
Biological buffer systems
Most biological fluids of the body are able to maintain the pH value under minor external influences, since they are buffer solutions.
A buffer solution is a solution containing a protolytic equilibrium system capable of maintaining a virtually constant pH value when diluted or when small amounts of acid or alkali are added.
In protolytic buffer solutions, the components are a proton donor and a proton acceptor, which are a conjugate acid-base pair.
Based on whether the weak electrolyte belongs to the class of acids or bases, buffer systems are divided into acidic and basic.
Acidic buffer systems are solutions containing a weak acid (proton donor) and a salt of this acid (proton acceptor). Acidic buffer solutions can contain different systems: acetate (CH3COO-, CH3COOH), hydrocarbonate (HCO3-, H2CO3), hydrophosphate (HPO22-, H2PO4-).
The main buffer systems are solutions containing weak bases (proton acceptor) and a salt of this base (proton donor).
Hydrocarbonate buffer system
The hydrocarbonate buffer system is formed by carbon monoxide (IV).
CO2 + H2O- CO2 H2O - H2CO3- H+ + HCO3-
In this system, the proton donor is carbonic acid H2CO3, and the proton acceptor is the bicarbonate ion HCO3-. Taking into account physiology, conventionally all CO2 in the body, both simply dissolved and hydrated to carbonic acid, is usually considered as carbonic acid.
Carbonic acid at a physiological pH = 7.40 is found predominantly in the form of a monoanion, and the ratio of the concentrations of components in the bicarbonate buffer system of the blood is [HCO3-]\ = 20:1. Consequently, the hydrocarbonate system has a buffer capacity for acid significantly greater than the buffer capacity for base. This corresponds to the characteristics of our body.
If acid enters the blood and the concentration of hydrogen ion increases, then it interacts with HCO3-, shifts it towards H2CO3 and leads to the release of carbon dioxide gas, which is released from the body during breathing through the lungs.
Н+ + НСО3- - Н2СО3 - СО2^ + Н2О
When bases enter the blood, they bind to carbonic acid, and the equilibrium shifts towards HCO3-.
OH- + H2CO3 - HCO3- + H2O
The main purpose of a bicarbonate buffer is to neutralize acids. It is a quick and effective response system, since the product of its interaction with acids - carbon dioxide - is quickly eliminated through the lungs. Violation of the acid-base balance in the body is primarily compensated with the help of a bicarbonate buffer system (10-15 min.)
The bicarbonate buffer is the main buffer system of the blood plasma, providing about 55% of the total buffer capacity of the blood. The bicarbonate buffer is also found in red blood cells, intercellular fluid and renal tissue.
Hydrogen phosphate buffer system
The hydrogen phosphate buffer system is found both in the blood and in the cellular fluid of other tissues, especially the kidneys. In cells it is represented by K2HPO4 and KH2PO4, and in blood plasma and intercellular fluid
Na2HPO4 and NaH2PO4. The role of the proton donor in this system is played by the H2PO4- ion, and the acceptor role is played by the HPO42- ion.
Normally, the ratio of forms [HPO42-]\[H2PO4-] = 4:1. Consequently, this system also has a buffer capacity for acids greater than for bases. When the concentration of hydrogen cations in the intracellular fluid increases, for example as a result of processing meat foods, they are neutralized by HPO42- ions.
H+ + HPO42- - H2PO4-
The resulting excess dihydrogen phosphate is excreted by the kidneys, which leads to a decrease in urine pH.
When the concentration of bases in the body increases, for example when eating plant foods, they are neutralized by H2PO4- ions
OH- + H2PO4- - HPO42-+ H2O
The resulting excess hydrogen phosphate is excreted by the kidneys, and the pH of the urine increases.
Unlike the hydrocarbonate system, the phosphate system is more “conservative”, since excess neutralization products are excreted through the kidneys and complete restoration of the [HPO42-]\[H2PO4-] ratio occurs only after 2-3 days. The duration of pulmonary and renal compensation for disturbances in the ratio of components in buffer systems must be taken into account during the therapeutic correction of disturbances in the acid-base balance of the body.
Hemoglobin buffer system
The hemoglobin buffer system is a complex buffer system of erythrocytes, which includes two weak acids as a proton donor: hemoglobin HHb and oxyhemoglobin HHbO2. the role of a proton acceptor is played by the bases conjugate to these acids, i.e. their anions Hb- and HbO2-.
Н+ + Нb-ННb Н+ + НbО2- - ННb + О2
When acids are added, the hemoglobin anions, which have a high affinity for protons, will absorb H+ ions first. When exposed to a base, oxyhemoglobin will exhibit greater activity than hemoglobin.
OH- + HHbO2 - HbO2- + H2O OH- + HHb- Hb- + H2O
Thus, the hemoglobin blood system plays a significant role in several of the body’s most important physiological processes: respiration, oxygen transport in tissues and maintaining a constant pH inside red blood cells, and ultimately in the blood. This system functions effectively only in combination with other buffer systems of the body.
Protein buffer systems
Protein buffer systems, depending on the acid-base properties of the protein, characterized by its isoelectric point, are of anionic and cationic types.
Anionic The protein buffer operates at pH>pIprotein and consists of a proton donor, the HProt protein molecule, which has a bipolar ionic structure, and a proton acceptor, the Prot- anion.
H3N+ – Prot – COOH - H+ + H3N – Prot – COO-
briefly Н2Рrot - Н+ + (НРrot) -
When an acid is added, this equilibrium shifts towards the formation of a protein molecule, and when a base is added, the content of the protein anion in the system increases.
Cationic protein buffer system works at pH<рIбелка и состоит из донора протона – катиона белка Н2Рrot и акцептора протона - молекулы белка НРrot.
H3N+ – Prot – COOH- H+ + H3N – Prot – COO-
briefly (Н2Рrot)+ + НРrot
Cationic the buffer system HProt, (H2Prot)+ usually maintains the pH value in physiological environments with pH< 6, а анионная белковая буферная система (Рrot)- , НРrot – в средах с рН >6. An anionic protein buffer works in the blood.
Acidosis
Acidosis (from Latin acidus - sour) is a shift in the body's acid-base balance towards increasing acidity (decreasing pH).
Causes of acidosis
Typically, the oxidation products of organic acids are quickly removed from the body. In case of febrile diseases, intestinal disorders, pregnancy, fasting, etc., they are retained in the body, which is manifested in mild cases by the appearance of acetoacetic acid and acetone in the urine (the so-called acetonuria), and in severe cases (for example, with diabetes) can lead to to a coma.
characterized by an absolute or relative excess of acids, i.e. substances that donate hydrogen ions (protons) in relation to the bases that attach them.
Acidosis can be compensated or uncompensated depending on the pH value - the hydrogen indicator of the biological environment (usually blood), expressing the concentration of hydrogen ions. With compensated acidosis, the blood pH shifts to the lower limit of the physiological norm (7.35). With a more pronounced shift to the acidic side (pH less than 7.35), acidosis is considered uncompensated. This shift is due to a significant excess of acids and insufficiency of physicochemical and physiological mechanisms for regulating acid-base balance. (Acid-base balance)
By origin, aluminum can be gas, non-gas, or mixed. Gas A. occurs as a result of alveolar hypoventilation (insufficient removal of CO2 from the body) or as a result of inhalation of air or gas mixtures containing high concentrations of carbon dioxide. At the same time, the partial pressure of carbon dioxide (pCO2) in arterial blood exceeds the maximum normal values (45 mm Hg), i.e. hypercapnia occurs.
Non-gas A. is characterized by an excess of non-volatile acids, a primary decrease in the bicarbonate content in the blood and the absence of hypercapnia. Its main forms are metabolic, excretory and exogenous acidosis.
Metabolic A. occurs due to the accumulation of excess acidic products in tissues, their insufficient binding or destruction; with an increase in the production of ketone bodies (ketoacidosis), lactic acid (lactic acidosis) and other organic acids. Ketoacidosis develops most often with diabetes mellitus, as well as with fasting (especially carbohydrate), high fever, severe insulin hypoglycemia, with certain types of anesthesia, alcohol intoxication, hypoxia, extensive inflammatory processes, injuries, burns, etc. Lactic acidosis occurs most often . Short-term lactic acidosis occurs during intense muscle work, especially in untrained people, when the production of lactic acid increases and its insufficient oxidation occurs due to a relative lack of oxygen. Long-term lactic acidosis is observed with severe liver damage (cirrhosis, toxic dystrophy), cardiac decompensation, as well as with a decrease in oxygen supply to the body due to insufficient external respiration and other forms of oxygen starvation. In most cases, metabolic A. develops as a result of an excess of several acidic foods in the body.
Excretory A., as a result of a decrease in the excretion of non-volatile acids from the body, is observed in kidney diseases (for example, in chronic diffuse glomerulonephritis), leading to difficulty in removing acid phosphates and organic acids. Increased excretion of sodium ions in the urine, which causes the development of renal A., is observed under conditions of inhibition of the processes of acidogenesis and ammoniagenesis, for example, with long-term use of sulfonamide drugs and some diuretics. Excretory A. (gastroenteral form) can develop with increased loss of bases through the gastrointestinal tract, for example, with diarrhea, persistent vomiting of alkaline intestinal juice thrown into the stomach, as well as with prolonged increased salivation. Exogenous A. occurs when a large number of acidic compounds are introduced into the body, incl. some medications.
The development of mixed forms of oxygen (a combination of gas and various types of non-gas oxygen) is due, in particular, to the fact that CO2 diffuses through alveolar capillary membranes approximately 25 times more easily than O2. Therefore, the difficulty in releasing CO2 from the body due to insufficient gas exchange in the lungs is accompanied by a decrease in blood oxygenation and, consequently, the development of oxygen starvation with the subsequent accumulation of under-oxidized products of interstitial metabolism (mainly lactic acid). Such forms of A. are observed in pathologies of the cardiovascular or respiratory systems.
Moderate compensated A. is practically asymptomatic and is recognized by examining the blood buffer systems, as well as the composition of urine. When A. deepens, one of the first clinical symptoms is increased breathing, which then turns into severe shortness of breath, pathological forms of breathing. Uncompensated A. is characterized by significant disorders of the functions of the central nervous system, cardiovascular system, gastrointestinal tract, etc. A. leads to an increase in the content of catecholamines in the blood, therefore, when it appears, an increase in cardiac activity, increased heart rate, increased minute blood volume, blood pressure rise. As A. deepens, the reactivity of adrenergic receptors decreases, and despite the increased content of catecholamines in the blood, cardiac activity is depressed, and blood pressure drops. In this case, various types of cardiac arrhythmias often occur, including ventricular fibrillation. In addition, A. leads to a sharp increase in vagal effects, causing bronchospasm, increased secretion of the bronchial and digestive glands; Vomiting and diarrhea often occur. In all forms of A., the oxyhemoglobin dissociation curve shifts to the right, i.e. the affinity of hemoglobin for oxygen and its oxygenation in the lungs decrease.
Under A. conditions, the permeability of biological membranes changes; some hydrogen ions move inside the cells in exchange for potassium ions, which are cleaved from proteins in an acidic environment. The development of hyperkalemia in combination with a low potassium content in the myocardium leads to a change in its sensitivity to catecholamines, drugs and other influences. With uncompensated A., severe disorders of the central nervous system function are observed. - dizziness, drowsiness, loss of consciousness and severe disorders of autonomic functions.
Alkalosis
Alkalosis (Late Latin alcali alkali, from Arabic al-quali) is a violation of the acid-base balance of the body, characterized by an absolute or relative excess of bases.
Classification
Alkalosis can be compensated or uncompensated.
Compensated alkalosis is a violation of the acid-base balance, in which the blood pH is kept within normal values (7.35-7.45) and only shifts in buffer systems and physiological regulatory mechanisms are noted.
With uncompensated alkalosis, the pH exceeds 7.45, which is usually associated with a significant excess of bases and insufficiency of physicochemical and physiological mechanisms for regulating acid-base balance.
Etiology
Based on the origin of alkalosis, the following groups are distinguished.
Gas (respiratory) alkalosis
It occurs as a result of hyperventilation of the lungs, leading to excessive removal of CO2 from the body and a drop in the partial tension of carbon dioxide in the arterial blood below 35 mm Hg. Art., that is, to hypocapnia. Hyperventilation of the lungs can be observed with organic lesions of the brain (encephalitis, tumors, etc.), the effect on the respiratory center of various toxic and pharmacological agents (for example, some microbial toxins, caffeine, corazol), with elevated body temperature, acute blood loss, etc.
Non-gas alkalosis
The main forms of non-gas alkalosis are: excretory, exogenous and metabolic. Excretory alkalosis can occur, for example, due to large losses of acidic gastric juice due to gastric fistulas, uncontrollable vomiting, etc. Excretory alkalosis can develop with long-term use of diuretics, certain kidney diseases, as well as endocrine disorders leading to excessive sodium retention in the body. In some cases, excretory alkalosis is associated with increased sweating.
Exogenous alkalosis is most often observed with excessive administration of sodium bicarbonate to correct metabolic acidosis or neutralize increased gastric acidity. Moderate compensated alkalosis can be caused by prolonged consumption of food containing many bases.
Metabolic alkalosis occurs in certain pathological conditions accompanied by disturbances in electrolyte metabolism. Thus, it is observed during hemolysis, in the postoperative period after some extensive surgical interventions, in children suffering from rickets, hereditary disorders of the regulation of electrolyte metabolism.
Mixed alkalosis
Mixed alkalosis (a combination of gas and non-gas alkalosis) can be observed, for example, with brain injuries accompanied by shortness of breath, hypocapnia and vomiting of acidic gastric juice.
Pathogenesis
With alkalosis (especially associated with hypocapnia), general and regional hemodynamic disturbances occur: cerebral and coronary blood flow decreases, blood pressure and minute volume decrease. Neuromuscular excitability increases, muscle hypertonicity occurs, up to the development of convulsions and tetany. Suppression of intestinal motility and the development of constipation are often observed; the activity of the respiratory center decreases. Gas alkalosis is characterized by decreased mental performance, dizziness, and fainting may occur.
Therapy for gas alkalosis consists of eliminating the cause that caused hyperventilation, as well as directly normalizing the gas composition of the blood by inhaling mixtures containing carbon dioxide (for example, carbogen). Therapy for non-gas alkalosis depends on its type. Solutions of ammonium, potassium, calcium chlorides, insulin, and agents that inhibit carbonic anhydrase and promote the excretion of sodium and bicarbonate ions by the kidneys are used.
Conclusion
In conclusion, it should be noted that in the human body, due to the processes of respiration and digestion, there is a constant formation of two opposites: acids and bases, mostly weak ones, which ensures a balanced character for the protolytic processes occurring in the body. At the same time, acid-base products are constantly eliminated from the body, mainly through the lungs and kidneys. Due to the balance of the processes of entry and removal of acids and bases, as well as due to the equilibrium nature of the protolytic processes that determine the interaction of these two opposites, the body maintains a state of protolytic (acid-base) homeostasis.
Bibliography:
V.I. Slesarev “Chemistry: Fundamentals of the chemistry of living things: Textbook for universities” - St. Petersburg: Khimizdat, 2000.
V.A. Popkov, S.A. Puzakov “General chemistry: textbook” - M.: GEOTAR-Media, 2009.
Yu.A. Ershov, V.A. Popkov, A.S. Berlyand and others; Ed. Yu.A. Ershova “General chemistry. Biophysical chemistry. Chemistry of biogenic elements" - M.: Higher school, 1993
Internet resources:
“Alkalosis”, “Acidosis” - http://ru.wikipedia.org/wiki
The protein buffer system is a combination of albumins and globulins - proteins that make up the bulk of blood plasma (~90%).
The isoelectric points of these proteins lie in the range of pH values = 4.9-6.3, i.e., in a slightly acidic environment. Therefore, under physiological conditions (at pH = 7.4), proteins are predominantly in the protein-base and salt forms of the protein-base.
Corresponding acid-base balance:
shifted towards the predominance of the protein-base form.
The buffer capacity determined by plasma proteins depends on the concentration of proteins, their secondary and tertiary structure and the number of free proton-acceptor groups. This system can neutralize both acidic and basic foods. However, due to the predominance of the “protein-base” form, its buffer capacity is significantly higher for acid and is: for albumins = 10 mmol/l, and for globulins = 3 mmol/l.
4. Amino acid buffer system.
The buffering capacity of free amino acids in blood plasma is insignificant for both acid and alkali. This is due to the fact that almost all amino acids have 
, noticeably different from 7.4. Therefore, at a physiological pH value = 7.4, their power is low. Almost only one amino acid is histidine ( 
= 6.0) - has a significant buffering effect at pH values close to the pH of blood plasma.
Thus, the power of blood plasma buffer systems decreases in the following order:
bicarbonate > protein > phosphate > amino acid
Red blood cells
In the internal environment of erythrocytes, pH = 7.25 corresponds to the norm. Hydrocarbonate and phosphate buffer systems also operate here. However, their potency differs from that in blood plasma. In addition, the protein system plays an important role in erythrocytes hemoglobin-oxyhemoglobin, which accounts for about 75% of the total buffer capacity of the blood.
Hemoglobin is a weak acid ( 
= 8.2) and dissociates according to the equation:
HHb ⇄H + + Hb -
At a physiological pH value = 7.25, this is described by the Henderson-Hasselbach equation:
,
from which it is clear that:
.
Thus, at pH = 7.25, the acid HHb is dissociated by only 10% and the concentration of the salt form of hemoglobin (Hb -) is significantly less than the concentration of the acid (HHb).
The HHb/Hb system can actively neutralize acidic and basic metabolic products, but has a higher capacity for alkali than for acid.
In the lungs, hemoglobin reacts with oxygen. In this case, oxyhemoglobin HHbO 2 is formed:
HHb +O 2 ⇄HHbО 2,
which is carried by arterial blood into capillary vessels, from where oxygen enters the tissues.
Oxyhemoglobin is a weak acid ( = 6.95), but significantly stronger than hemoglobin ( 
= 8.2). At a physiological pH value = 7.25 acid-base balance:
HHbО 2 ⇄H + + HbО 2 -
corresponds to the Henderson-Hasselbach equation:
.
From this we can conclude that C(HbO 2 -)/C(HHbO 2) = 2:1 and the proportion of dissociated HHbO 2 molecules is approximately 65%.
When adding acids, hemoglobin anions Hb - will neutralize H + ions first:
Hb - + H + ⇄ HHb,
since they have a greater affinity for protons than HbO 2 - ions.
When exposed to bases, the stronger acid oxyhemoglobin HHbO 2 will react first:
HHbO 2 + OH - ⇄ HbO 2 - + H 2 O,
however, hemoglobin acid will also participate in the neutralization of OH - ions entering the blood:
HHb + OH - ⇄ Hb - + H 2 O.
The hemoglobin-oxyhemoglobin system plays an important role both in the process of respiration (the transport function of transporting oxygen to tissues and organs and removing metabolic CO 2 from them), and in maintaining a constant pH inside red blood cells, and as a result, in the blood as a whole.
In the human body, all buffer systems are interconnected. Thus, in erythrocytes, the hemoglobin-oxyhemoglobin buffer system is closely related to the bicarbonate buffer system. Since the pH inside erythrocytes is 7.25, the ratio of the concentrations of salt (HCO 3 -) and acid H 2 CO 3 here is slightly less than in blood plasma. Indeed, from the Henderson-Hasselbach equation it follows that in erythrocytes C(HCO 3 -)/C(H 2 CO 3) = 14:1. However, although the acid buffering capacity of this system within red blood cells is somewhat less than that of plasma, it is effective in maintaining a constant pH.
The phosphate buffer system plays a much more important role in blood cells than in blood plasma. First of all, this is due to the fact that red blood cells contain a large amount of inorganic phosphates, mainly KH 2 PO 4 and K 2 HPO 4. In addition, esters of phosphoric acids play a major role in maintaining a constant pH, mainly phospholipids, which form the basis of red blood cell membranes.
Phospholipids are relatively weak acids. Values phosphate groups range from 6.8 to 7.2. Consequently, at a physiological pH value = 7.25, the phospholipids of erythrocyte membranes are found both in the form of non-ionized and ionized forms, i.e. in the form of a weak acid and its salt. In this case, the ratio of salt and acid concentrations is approximately (1.5-4):1. Thus, the erythrocyte membrane itself has a buffering effect and maintains a constant pH of the internal environment of erythrocytes.
In cases where the body's buffer and excretory defenses exhaust their capabilities and a severe form of acidosis (alkalosis) develops, they resort to drug suppression of these disorders. Thus, in case of gaseous acidosis, basic drugs are administered intravenously, which are salts of weak acids: 4% solution of NaHCO 3, solution of sodium salt of citric acid - sodium citrate (Na 3 Cit), etc., which neutralize excess acidity by binding ions H+ to weak acids:
H + + HCO 3 - 
H2CO3 H2O+CO2
Elimination of the metabolic form of acidosis is also carried out by introducing salts of weak acids and other drugs that have the property of passing through phospholipid membranes.
For alkalosis, solutions of weak acids are administered, for example, a 4% solution of ascorbic acid.
However, the listed methods of drug intervention do not, strictly speaking, have a therapeutic effect: they only allow you to “gain time” for a more detailed identification of the causes of deviations and the prescription of a course of treatment or prevention.
The phosphate buffer system plays a significant role in the regulation of ASR inside cells, especially in kidney tubules. This is due to the higher concentration of phosphates in the cells compared to the extracellular fluid (about 8% of the total buffer capacity). The phosphate buffer consists of two components: alkaline - (Na 2 HPO 4) and acidic - (NaH 2 PO 4).
The renal tubular epithelium contains buffer components in maximum concentration, which ensures its high power. In the blood, the phosphate buffer helps maintain (“regenerate”) the bicarbonate buffer system. With an increase in the level of acids in the blood plasma (containing both bicarbonate and phosphate buffers), the concentration of H 2 CO 3 increases and the content of NaHCO 3 decreases:
H 2 CO 3 + Na 2 HPO 4 NaHCO 3 + NaH 2 PO 4
As a result, excess carbonic acid is eliminated and the NaHCO 3 level increases.
Protein buffer system
The protein buffer system is the main intracellular buffer. It constitutes approximately three-quarters of the buffering capacity of intracellular fluid.
The components of the protein buffer are a weakly dissociating protein with acidic properties (protein-COOH) and salts of a strong base (protein-COONa). As the level of acids increases, they interact with the protein salt to form a neutral salt and a weak acid. When the concentration of bases increases, their reaction occurs with a protein with acidic properties. As a result, a weakly basic salt is formed instead of a strong base.
Hemoglobin buffer system
The hemoglobin buffer system, the most capacious blood buffer, accounts for more than half of its total buffer capacity. The hemoglobin buffer consists of an acidic component - oxygenated Hb - HbO 2 and a basic component - non-oxygenated. HbO 2 dissociates about 80 times more strongly with the release of H + into the environment than Hb. Accordingly, it binds more cations, mainly K +.
The main role of the hemoglobin buffer system is its participation in the transport of CO 2 from tissues to the lungs.
In the capillaries of the systemic circulation HbO 2 gives up oxygen. In red blood cells, CO 2 interacts with H 2 O and H 2 CO 3 is formed. This acid dissociates into HCO 3 – and H +, which combines with Hb. HCO 3 – anions leave erythrocytes in the blood plasma, and an equivalent amount of Cl – anions enters erythrocytes. The Na + ions remaining in the blood plasma interact with HCO 3 - and thereby restore its alkaline reserve.
In the capillaries of the lungs, under conditions of low pCO 2 and high pO 2, Hb adds oxygen to form HbO 2. The carbamine bond is broken, releasing CO 2 . At the same time, HCO 3 – from the blood plasma enters the erythrocytes (in exchange for Cl – ions) and interacts with H +, split off from Hb at the time of its oxygenation. The resulting H 2 CO 3 under the influence of carbonic anhydrase is split into CO 2 and H 2 O. CO 2 diffuses into the alveoli and is excreted from the body.
Bone carbonates
Bone carbonates function as a depot for the body's buffer systems. Bones contain a large amount of carbonic acid salts: calcium, sodium, potassium carbonates, etc. With an acute increase in acid content (for example, in acute cardiac, respiratory or renal failure, shock, coma and other conditions), bones can provide up to 30–40% buffer capacity. The release of calcium carbonate into the blood plasma helps to effectively neutralize excess H +. Under conditions of chronic load with acidic compounds (for example, in chronic cardiac, hepatic, renal, respiratory failure), bones can provide up to 50% of the buffer capacity of the body's biological fluids.
PHYSIOLOGICAL MECHANISMS
Along with powerful and fast-acting chemical systems, organ mechanisms function in the body to compensate and eliminate shifts in CBS. To implement them and achieve the desired effect, more time is required - from several minutes to several hours. The most effective physiological mechanisms for regulating CBS include processes occurring in the lungs, kidneys, liver and gastrointestinal tract.
Lungs
The lungs eliminate or reduce shifts in the respiratory tract by changing the volume of alveolar ventilation. This is a fairly mobile mechanism - within 1–2 minutes after changing the volume of alveolar ventilation, shifts in the CBS are compensated or eliminated.
The reason for the change in breathing volume is a direct or reflex change in the excitability of the neurons of the respiratory center.
Decrease in pH in body fluids(blood plasma, CSF) is a specific reflex stimulus for increasing the frequency and depth of respiratory movements. As a result, the lungs release excess CO 2 (formed during the dissociation of carbonic acid). As a result, the content of H + (HCO 3 – + H + = H 2 CO 3 ® H 2 O + CO 2) in the blood plasma and other body fluids decreases.
Increasing pH in body fluids reduces the excitability of inspiratory neurons of the respiratory center. This leads to a decrease in alveolar ventilation and the removal of CO 2 from the body, i.e. to hypercapnia. In this regard, in the liquid media of the body, the level of carbonic acid, which dissociates with the formation of H +, increases, and the pH decreases.
Consequently, the external respiration system can quite quickly (within a few minutes) eliminate or reduce pH shifts and prevent the development of acidosis or alkalosis: doubling pulmonary ventilation increases the blood pH by about 0.2; a 25% reduction in ventilation can reduce pH by 0.3-0.4.
Kidneys
The main mechanisms for reducing or eliminating shifts in the blood metabolic rate realized by kidney nephrons include acidogenesis, ammoniogenesis, phosphate secretion and the K + , Na + exchange mechanism.
Acidogenesis. This energy-dependent process, occurring in the epithelium of the distal nephron and collecting ducts, secretes H + into the tubular lumen in exchange for reabsorbed Na + (Fig. 14-1).
LAYOUT Insert file " PF Fig. 14 01 Reabsorption of HCO3‑ in the cells of the proximal part »
Rice.14–1 .Reabsorption of HCO 3‑ in the cells of the proximal part.
CA - carbonic anhydrase.
LAYOUT Insert file " PF Fig. 14 02 Reabsorption of HCO3‑ in the cells of the proximal part »
Rice.14–2 .Secretion of H+ by tubule and collecting duct cells.
CA - carbonic anhydrase.
The amount of secreted H + is equivalent to the amount that enters the blood with non-volatile acids and H 2 CO 3. Na + reabsorbed from the lumen of the tubules into the blood plasma is involved in the regeneration of the plasma bicarbonate buffer system (Fig. 13–2).
Ammoniogenesis, like acidogenesis, is realized by the epithelium of the nephron tubules and collecting ducts. Ammoniogenesis is carried out by oxidative deamination of amino acids, predominantly (about 2/3) glutamine, and to a lesser extent alanine, asparagine, leucine, and histidine. The ammonia formed during this process diffuses into the lumen of the tubules. There, NH 3 + attaches to an H + ion to form ammonium ion (NH 4 +). NH 4 + ions replace Na + in salts and are released mainly in the form of NH 4 Cl and (NH 4) 2 SO 4. In this case, an equivalent amount of sodium bicarbonate enters the blood, ensuring the regeneration of the bicarbonate buffer system.
Phosphate secretion carried out by the epithelium of the distal tubules with the participation of the phosphate buffer system:
Na 2 HPO 4 + H 2 CO 3 NaH 2 PO 4 + NaHCO 3
The resulting sodium bicarbonate is reabsorbed into the blood and maintains the bicarbonate buffer, and NaH 2 PO 4 is excreted from the body in the urine.
Thus, the secretion of H + by the tubular epithelium during the implementation of the three mechanisms described above (acidogenesis, ammoniogenesis, phosphate secretion) is associated with the formation of bicarbonate and its entry into the blood plasma. This ensures the constant maintenance of one of the most important, capacious and mobile buffer systems - the hydrocarbonate one - and, as a result, the effective elimination or reduction of shifts in CBS that are dangerous to the body.
K + ,Na + -exchange mechanism, realized in the distal parts of the nephron and the initial sections of the collecting ducts, ensures the exchange of Na + in primary urine for K +, which is excreted into it by epithelial cells. Reabsorbed Na + in body fluids participates in the regeneration of the bicarbonate buffer system. K + ,Na + -exchange is controlled by aldosterone. In addition, aldosterone regulates (increases) the volume of H + secretion and excretion.
Thus, the renal mechanisms of eliminating or reducing shifts in the CBS are carried out by excreting H + and restoring the reserve of the bicarbonate buffer system in the body’s fluids.
Liver
The liver plays a significant role in compensating for changes in CBS. On the one hand, common intra- and extracellular buffer systems (hydrocarbonate, protein, etc.) operate in it; on the other hand, various metabolic reactions are carried out in hepatocytes that are directly related to the elimination of CBS disorders.
Blood protein synthesis, included in the protein buffer system. All albumins are formed in the liver, as well as fibrinogen, prothrombin, proconvertin, proaccelerin, heparin, a number of globulins and enzymes.
Ammonia formation, capable of neutralizing acids both in the hepatocytes themselves and in the blood plasma and intercellular fluid.
Glucose synthesis from non-carbohydrate substances - amino acids, glycerol, lactate, pyruvate. The inclusion of these organic non-volatile acids during the formation of glucose ensures a decrease in their content in cells and biological fluids. Thus, UA, which many organs and tissues are not able to metabolize, is approximately 80% transformed in hepatocytes into H 2 O and CO 2, and the remaining amount is resynthesized into glucose. Thus, lactate is converted into neutral products.
Removing non-volatile acids from the body- glucuronic and sulfuric acid for detoxification of metabolic products and xenobiotics.
Excretion into the intestine acidic and basic substances with bile.
Stomach and intestines
The stomach participates in damping the shifts of acid-rich acid, mainly by changing the secretion of hydrochloric acid: when the body fluids become alkalized, this process is inhibited, and when acidified, it intensifies. The intestine helps to reduce or eliminate shifts in acid-rich hormones by:
Secretion of intestinal juice, containing large amounts of bicarbonate. At the same time, H + enters the blood plasma.
Changes in the amount of fluid absorbed. This helps to normalize the water and electrolyte balance in cells, extracellular and other biological fluids and, as a result, normalize pH.
Reabsorption of components of buffer systems(Na +, K +, Ca 2+, Cl –, HCO 3 –).
Related information.
In the human body, as a result of various metabolic processes, large quantities of acidic products are constantly formed. The average daily rate of their excretion corresponds to 20-30 liters of a strong acid solution with a molar concentration of the chemical equivalent of the acid equal to 0.1 mol/l (or 2000-3000 mmol of the chemical equivalent of the acid).
In this case, the main products are also formed: ammonia, urea, creatine, etc., but only to a much lesser extent.
The composition of acidic metabolic products includes both inorganic (H 2 CO 3, H 2 SO 4) and organic (lactic, butyric, pyruvic, etc.) acids.
Hydrochloric acid is secreted by parietal glandulocytes and released into the gastric cavity at a rate of 1-4 mmol/hour.
Carbonic acid is the end product of the oxidation of lipids, carbohydrates, proteins and various other bioorganic substances. In terms of CO 2, up to 13 moles are formed daily.
Sulfuric acid is released during the oxidation of proteins, since they contain sulfur-containing amino acids: methionine, cysteine.
When 100 g of protein is digested, about 60 mmol of the chemical equivalent of H 2 SO 4 is released.
Lactic acid is formed in large quantities in muscle tissue during physical activity.
From the intestines and tissues, acidic and basic products formed during metabolism constantly enter the blood and intercellular fluid. However, acidification of these media does not occur and their pH value is maintained at a certain constant level.
Thus, the pH values of most intracellular fluids are in the range from 6.4 to 7.8, the intercellular fluid - 6.8-7.4 (depending on the type of tissue).
Particularly stringent restrictions on possible fluctuations in pH values are imposed on blood. The normal state corresponds to the range of pH values = 7.4±0.05.
The constancy of the acid-base composition of biological fluids of the human body is achieved through the combined action of various buffer systems and a number of physiological mechanisms. The latter primarily include the activity of the lungs and the excretory function of the kidneys, intestines, and skin cells.
The main buffer systems of the human body are: hydrocarbonate (bicarbonate), phosphate, protein, hemoglobin and oxyhemoglobin. They are present in various quantities and combinations in one or another biological fluid. Moreover, only blood contains all four systems.
Blood is a suspension of cells in a liquid medium and therefore its acid-base balance is maintained by the joint participation of plasma buffer systems and blood cells.
Bicarbonate buffer system is the most regulated blood system. It accounts for about 10% of the total buffer capacity of the blood. It is a conjugated acid-base pair consisting of hydrates of CO 2 molecules (CO 2 · H 2 O) (acting as proton donors) and bicarbonate ions HCO 3 - (acting as a proton acceptor).
Hydrocarbonates in blood plasma and other intercellular fluids are found mainly in the form of sodium salt NaHCO 3, and inside cells - potassium salt.
The concentration of HCO 3 - ions in the blood plasma exceeds the concentration of dissolved CO 2 by approximately 20 times.
When relatively large amounts of acidic products are released into the blood, H + ions interact with HCO 3 –.
H + + HCO 3 – = H 2 CO 3
A subsequent decrease in the concentration of the resulting CO 2 is achieved as a result of its accelerated release through the lungs as a result of their hyperventilation.
If the amount of basic products in the blood increases, then they interact with weak carbonic acid:
H 2 CO 3 + OH – → HCO 3 – + H 2 O
At the same time, the concentration of dissolved carbon dioxide in the blood decreases. To maintain a normal ratio between the components of the buffer system, a physiological retention of a certain amount of CO 2 occurs in the blood plasma due to hypoventilation of the lungs.
Phosphate buffer system is a conjugate acid-base pair H 2 PO 4 – /HPO 4 2– .
The role of the acid is performed by sodium dihydrogen phosphate NaH 2 PO 4 , and the role of its salt is sodium hydrogen phosphate Na 2 HPO 4 . The phosphate buffer system makes up only 1% of the buffering capacity of the blood. The ratio C(H 2 PO 4 –)/C(HPO 4 2–) in it is 1: 4 and does not change over time, because an excess amount of any of the components is excreted in the urine, however, this occurs in within 1-2 days, i.e. not as fast as with a bicarbonate buffer.
The phosphate buffer system plays a decisive role in other biological environments: some intracellular fluids, urine, secretions (or juices) of the digestive glands.
Protein buffer is a system of protein (protein) molecules containing in their amino acid residues both acidic COOH groups and basic NH 2 groups, acting as a weak acid and base. The components of this buffer can be conventionally expressed as follows:
|
Pt-COOH/Pt-COO – |
||||
|
weakly dissociated protein-acid |
salt formed by a strong base | |||
|
(Pt-NH 2 /Pt-NH 3 + |
||||
|
weakly dissociated protein base |
salt formed by a strong acid |
Thus, the protein buffer is amphoteric in composition. With an increase in the concentration of acidic products, both protein–salt (Pt-COO –) and protein–base (Pt-NH 2) can interact with H + ions:
Pt-COO – + H + → Pt-COOH
Pt-NH 2 + H + → Pt-NH 3 +
Neutralization of the main metabolic products is carried out due to interaction with OH ions - both protein-acid (Pt-COOH) and protein-salt (Pt-NH 3 +)
Pt-COOH +OH – →Pt-COO – + H 2 O
Pt-NH 3 + +OH – →Pt-NH 2 + H 2 O
Thanks to proteins, all cells and tissues of the body have a certain buffering effect. In this regard, a small amount of acid or alkali that gets on the skin is quickly neutralized and does not cause a chemical burn.
The most powerful blood buffer systems are hemoglobin and oxyhemoglobin buffers, which are found in erythrocytes. They account for approximately 75% of the total buffer capacity of the blood. By their nature and mechanism of action, they belong to protein buffer systems.
Hemoglobin buffer is present in venous blood and its composition can be roughly depicted as follows:
CO 2 and other acidic metabolic products entering the venous blood react with the potassium salt of hemoglobin.
KHв +CO 2 →KНСО 3 +HHв
Once in the capillaries of the lungs, hemoglobin is converted into oxyhemoglobin HHbO 2, attaching O 2 molecules to itself.
Oxyhemoglobin has stronger acidic properties than hemoglobin and carbonic acid. It interacts with potassium bicarbonate, displacing H 2 CO 3 from it, which breaks down into CO 2 and H 2 O. The resulting excess CO 2 is removed from the blood through the lungs.
HHbO 2 + KHCO 3 → KHbO 2 + H 2 CO 3
The hemoglobin and oxyhemoglobin buffer systems are interconvertible systems and exist as a single whole. They significantly contribute to maintaining the concentration of bicarbonate ions HCO 3 - (the so-called alkaline blood reserve) in the blood at a constant level.
One of the main parameters of homeostasis of the human body, the fluctuation rates of which lie within very small limits, is blood pH. Blood buffer systems immediately respond to changes in this indicator, returning it to normal. This interaction makes it possible to maintain the dynamic balance of the body along with such regulatory systems as, for example, thermoregulation.
Let's take a closer look at the blood buffer systems and the mechanism of their action.
What determines the pH level?
Such a well-known indicator of liquid media as pH, also called acid-base balance, is the main parameter regulating blood. Blood, like any liquid, contains free hydrogen ions:
- H - acidic ions, causing a low pH with an acidic reaction;
- OH are alkaline ions, causing a high pH with an alkaline reaction.
Water is an example of a neutral reaction with a pH of 7.0.
Blood pH standards
Plasma from healthy human blood is slightly alkaline with an average pH of 7.4. The body reacts to the slightest fluctuations in pH, which normally should be in the range from 7.35 to 7.45. Such narrow limits indicate how vital this blood sensor is. The gap in normal values is only due to the fact that venous and arterial blood have different pH. Indicators decrease in venous blood, which is saturated with cellular metabolic products that have an acidic reaction. Therefore, venous blood has a low pH compared to arterial blood.
Along with the above, it is worth noting that it is the blood hydrogen indicator that is one of the most stable in the human body. A shift in pH to a lower side (acidic) leads to acidosis, and to a higher one (alkaline) leads to alkalosis. These are very life-threatening conditions, since, according to research, the critical pH shift for maintaining life is only 0.4.
The whole point is that the body's enzymes are sensitive to pH and are active only in a certain environment. Therefore, the blood maintains optimal levels of hydrogen balance in all tissues, ensuring the correct level of metabolism. Disorder of the acid-base balance of the blood throws all body systems out of balance.
pH levels of other body systems
In other body systems there may be a completely different pH level.
- The most acidic environment is in the stomach: pH is in the range of 1.5-1.8. This is due to hydrochloric acid, which is necessary to digest food.
- Average values for the gallbladder and intestines: pH - about 5.0.
An organism is one large system whose components interact with each other. Therefore, blood pH is maintained at a certain level not only by blood buffer systems, but also by many other body processes. It is logical that even the consumption of protein or plant foods has different effects on the blood acid-base balance. Thus, most plant foods have alkalizing properties, while meat has oxidizing properties.
Buffer systems to protect pH levels
The main “specialists” regulating the level of hydrogen balance are the so-called blood buffer systems, the biochemistry of which has a special effect on the pH level. Among them, two main groups can be distinguished - proteins and inorganic compounds. Many of them work like scales, balancing the acid-base balance of the blood thanks to unique chemical compounds and the dual properties of protein molecules. The latter are able to change their behavior depending on the pH of the environment.
Main blood buffer systems:
- protein;
- hemoglobin;
- bicarbonate;
- phosphate
The mechanism of operation of buffer systems
The very principle of operation of buffer systems is very simple; its essence is to regulate the amount of free ions, binding them thanks to a certain buffer. Blood plasma buffer systems are proteins, which play a major role, and inorganic compounds.
If the blood pH drops to 7.0 (with the norm being 7.4), then the blood buffer systems begin to actively work. By binding excess free hydrogen ions, forming buffer complexes, they move through the circulatory system and unload in the lungs, kidneys, skin, digestive organs, etc. This buffer express unloads and removes excess acidic and alkaline products.
Hemoglobin and protein buffer
Has the most powerful effect hemoglobin system, which plays the role of an alkali in the capillaries of tissues, and in the lungs, giving up carbon dioxide, the role of an acid. The hemoglobin buffer system of the blood consists of free, reduced and oxidized hemoglobin, as well as carboxyhemoglobin. This buffer takes on the lion's share of all buffer processes in the blood.
The essence of the action of hemoglobin as a buffer lies in its globin component. It changes its properties when moving from one form of hemoglobin to another, while changing its acidic properties. Reduced hemoglobin is weaker than carbonic acid, while oxidized hemoglobin is stronger. When the blood pH becomes acidic, free hemoglobin binds H-ions, forming reduced hemoglobin.
When the blood in the lungs is filtered of carbon dioxide, the blood pH becomes alkaline again, and oxidized hemoglobin becomes a proton donor, stabilizing the acid-base balance from shifting to alkalinity.
Protein system works due to the special properties of plasma proteins - amphotericity. An acidic environment causes a protein to behave like an alkali, and an alkaline environment to behave like an acid.
Inorganic buffer systems
Bicarbonate buffer system blood has a chemical property that makes it two-way effective. It consists of a deterministic ratio of molecules of carbonic acid and bicarbonate anion. The system is included in the regulatory process only when an acid stronger than carbonic acid enters the blood. Then this acid binds with bicarbonate anions, transforming into salt and carbonic acid. When alkali enters the blood, it binds with carbonic acid and forms a bicarbonate salt.
Phosphate buffer system is a combination of sodium dihydrogen phosphate and sodium hydrogen phosphate. Dihydrogen phosphate exhibits the properties of a weak acid, and hydrogen phosphate exhibits the properties of an alkali. The system works similar to the bicarbonate system.
Buffer unloading location - lungs
In the lungs, as is known, carbon dioxide is released, which most directly affects the pH of the blood towards alkalization. In addition, the increased oxygen pressure and low carbon dioxide pressure pushes these hydrogen ions out of the blood into the air, which is exhaled. Free buffer systems will return to the bloodstream.
By increasing your breathing, this process can happen much faster. It only takes about 2-3 minutes to regulate the blood pH in the lungs. If we compare it with the processes of regulation of this indicator in the kidneys, it is almost lightning fast, because the kidneys will require many hours.
Place of buffer unloading - kidneys
In addition to the lungs, plasma buffers can be unloaded in the kidneys due to a very acidic pH reaction, which is equal to 4.5. The concentration of H-ions in urine is 800 times greater than in the blood. Now one can only imagine how actively the renal tubular epithelium must function in order to drive these hydrogen ions from the loaded plasma buffers into the urine. At the same time, the opposite process of returning OH ions from urine to the blood occurs through reabsorption.
Skin, intestines and other pathways of pH regulation
In addition to the pulmonary and renal mechanisms, the pH balance is maintained by the sweat glands, which utilize acidic substances. The intestine, with its alkaline environment, also takes an active part in this self-regulation, binding free acidic hydrogen ions.
There are many other ways to regulate this balance (for example, during physical activity). During training or physical labor, huge amounts of lactic acid are produced. But the blood does not become critically acidic, since the muscle arterioles immediately react by expanding. Blood flow increases, and at the same time the concentration of buffer systems, ready to bind excess acids, increases. This mechanism works in the same way in any other organs.
Blood buffer systems: standby mode
All the described elements are the simplest levels of self-regulatory activity of the body. We can say that these are lower levels intended to regulate pH in standby mode. What if these self-regulation links fail and the pH level begins to reach critical values - 0.7-7.8? Then the time comes to include other elements of a higher level.
SOS measures for pH regulation
When life-threatening indicators are received by the part of the brain responsible for breathing, “fire measures” are activated. Breathing becomes frequent and deep, increasing the release of excess carbon dioxide and free hydrogen ions. The sweat glands and endocrine glands significantly increase their work. As a result, the rate of metabolic processes in the body increases.
In addition, there are special hormones that are released into the blood, being strong catalysts that enhance the work of enzymes. The kidney tubules begin to more actively exchange hydrogen ions with the plasma. In a word, the entire body goes into a state of work in emergency mode, which ultimately brings all systems into balance.
The main thing is balance
The body is a unique self-regulating system, capable of returning itself to a state of normalcy in a huge variety of ways. You need to understand that the blood buffer systems themselves, the functions they perform, and the processes of maintaining pH are extremely important. Like any others, they can constantly operate in “fire” mode. Therefore, a person is obliged to eat properly and variedly. There are special tables with indicators of the influence of different food groups on the acid-base balance.
Don't get carried away with new ideas about alkalizing your blood by eating only certain foods. The main thing is a balanced diet, moderate physical activity and plenty of clean water. This will help the body's buffer systems to work more efficiently and smoothly, and the blood to be healthy.