All buffer systems of the body are involved in maintaining acid-base homeostasis (the balance of optimal concentrations of acidic and basic components of physiological systems). Their actions are interconnected and are in a state of balance. The hydrocarbonate buffer is most associated with all buffer systems. Disturbances in any buffer system affect the concentrations of its components, so changes in the parameters of the hydrocarbonate buffer system can quite accurately characterize the body's CBS.
Blood CBS is normally characterized by the following metabolic parameters:
Plasma pH 7.4±0.05;
[НСО 3 - ]=(24.4±3) mol/l - alkaline reserve;
pCO 2 =40 mm Hg - partial pressure of CO 2 above the blood.
From the Henderson-Hasselbach equation for a bicarbonate buffer, it is obvious that when the concentration or partial pressure of CO 2 changes, the blood CBS changes.
Maintaining the optimal value of the environmental reaction in various parts of the body is achieved through the coordinated work of buffer systems and excretory organs. A shift in the reaction of the medium to the acidic side is called acidosis, and basically – alkalosis. The critical values for preserving life are: shift to the acidic side up to 6,8 , and basically – 8,0 . Acidosis and alkalosis can be respiratory or metabolic in origin.
Metabolic acidosis develops due to:
a) increased production of metabolic acids;
b) as a result of loss of bicarbonates.
Increased production of metabolic acids occurs when:
1. diabetes mellitus type I, prolonged, complete fasting or a sharp reduction in the proportion of carbohydrates in the diet;
2. lactic acidosis (shock, hypoxia, type II diabetes mellitus, heart failure, infections, alcohol poisoning).
Increased loss of bicarbonates possible with urine (renal acidosis), or with some digestive juices (pancreatic, intestinal).
Respiratory acidosis develops with hypoventilation of the lungs, which, regardless of the cause that caused it, leads to an increase in the partial pressure of CO 2 more than 40 mm Hg. Art. ( hypercapnia). This happens with diseases of the respiratory system, hypoventilation of the lungs, depression of the respiratory center with certain drugs, for example, barbiturates.
Metabolic alkalosis observed with significant losses of gastric juice due to repeated vomiting, as well as as a result of the loss of protons in the urine during hypokalemia, constipation (when alkaline products accumulate in the intestines; after all, the source of bicarbonate anions is the pancreas, the ducts of which open into the duodenum), as well as with long-term intake of alkaline foods and mineral water, the salts of which undergo anion hydrolysis.
Respiratory alkalosis develops as a result of hyperventilation of the lungs, leading to excessive removal of CO 2 from the body and a decrease in its partial pressure in the blood to less than 40 mm. rt. Art. ( hypocapnia). This happens when inhaling rarefied air, hyperventilation of the lungs, the development of thermal shortness of breath, excessive excitation of the respiratory center due to brain damage.
At acidosis as an emergency measure, intravenous infusion of 4 - 8% sodium bicarbonate, 3.66% solution of trisamine H 2 NC (CH 2 OH) 3 or 11% sodium lactate is used. The latter, while neutralizing acids, does not emit CO 2, which increases its effectiveness.
Alkaloses are more difficult to correct, especially metabolic ones (associated with disorders of the digestive and excretory systems). Sometimes a 5% solution of ascorbic acid is used, neutralized with sodium bicarbonate to pH 6 - 7.
Alkaline reserve- this is the amount of bicarbonate (NaHCO 3) (more precisely, the volume of CO 2 that can be bound by blood plasma). This value can only conditionally be considered as an indicator of acid-base balance, since, despite the increased or decreased bicarbonate content, in the presence of appropriate changes in H 2 CO 3, the pH can remain completely normal.
Since the compensatory capabilities through respiration initially used by the body are limited, the decisive role in maintaining constancy passes to the kidneys. One of the main tasks of the kidneys is to remove H + ions from the body in cases where, due to some reason, a shift towards acidosis occurs in the plasma.
Acidosis cannot be corrected unless the appropriate amount of H+ ions is removed. The kidneys use 3 mechanisms:
1. Exchange of hydrogen ions for sodium ions, which, combining with the HCO 3 anions formed in the tubular cells, are completely reabsorbed in the form of NaHCO 3,
The prerequisite for the release of H + ions using this mechanism is the carbonic anhydrase-activated reaction CO 2 + H 2 O = H 2 CO 3, and H 2 CO 3 decomposes into H + and HCO 3 - ions. During this exchange of hydrogen ions for sodium ions, all sodium bicarbonate filtered in the glomeruli is reabsorbed.
2. The excretion of hydrogen ions in the urine and the reabsorption of sodium ions also occurs through the conversion of the alkaline salt of sodium phosphate (Na 2 HPO 4) into the acid salt of sodium diphosphate (NaHaPO 4) in the distal tubules.
3. Formation of ammonium salts: ammonia, formed in the distal parts of the renal tubules from glutamine and other amino acids, promotes the release of H + ions and the reabsorption of sodium ions; NH 4 Cl is formed due to the combination of ammonia with HCl.
The intensity of ammonia formation, necessary to neutralize strong HCl, is greater, the higher the acidity of the urine.
Basic parameters of CBS
| pH | N ≈ 7.4 | (average value in arterial blood) |
| pCO 2 | 40 mm. rt. Art. (partial pressure of CO 2 in blood plasma) | This component directly reflects the respiratory component in the regulation of CBS (CAR). (hypercapnia) is observed with hypoventilation, which is characteristic of respiratory acidosis. ↓ (hypocapnia) is observed during hyperventilation, which is characteristic of respiratory alkalosis. However, changes in pCO 2 may also be a consequence of compensation from metabolic disorders of the CBS. To distinguish these situations from each other, it is necessary to consider pH and [HCO 3 -] |
| pO 2 | 95 mm. rt. Art. (partial pressure in blood plasma) | |
| SB or SB | 24 meq/l | SB – standard plasma bicarbonate i.e. [НСО 3 - ] ↓ - with metabolic acidosis, or with compensation of respiratory alkalosis. - with metabolic alkalosis or compensation of respiratory acidosis. |
Additional indexes
Normally, relatively speaking, there is neither a deficiency nor an excess of bases (neither DO nor IO). In fact, this is expressed in the fact that the difference between the expected and actual BO is under normal conditions within ±2.3 meq/l. The departure of this indicator from the normal range is typical for metabolic disorders of CBS. Abnormally high values are characteristic of metabolic alkalosis. Abnormally low – for metabolic acidosis.
Hello dear friends!
Today I would like to once again draw your attention to the main causes of our diseases. Most people continue to live absolutely incorrectly, without weighing the facts and without reflecting on the essence of their existence. They live like tumbleweeds, rolling with the wind of life, exchanging the days and years of their existence for vanity of vanities. They do not think about tomorrow, they do not try not only to somehow plan and predict their future, but even to dream about it. And of course, against the backdrop of such an existence, there is no room left for your health. Such people simply don’t think about it, knowing that there are doctors and clinics who will help.
What can you say about this? Rely on God, but you yourself are a bad guy! Hope in this case is absolutely the wrong approach to your own life. Our medicine in such cases is just an ambulance. And the result of such assistance, at best, can be fifty-fifty. There are no guarantees that you will not die after the first bell. The driver's ideology - where the road will take you - is not at all for those who intend to live long, interestingly and happily.
If you care when you pass into another world, or how many years before your death you will suffer with your sores, start taking care of yourself right today. And I am very glad if you have already understood how to treat yourself and your health and do everything systematically throughout the slowly flowing time of your life. Of course, we are talking primarily about your own actions aimed at creating your happy future and maintaining health for many, many years.
The key to health is your metabolism - homeostasis. And let's talk today about its parts that can be adjusted. A person must learn to manage his own health. And today there are all conditions for this! Well, let's hit the road? Most importantly, without lyrics and digressions. It is clear that this topic is worthy of a separate publication, but in this short article I will try to teach you to move in the right direction in order to maintain health and recovery. So, let's go...
The basic, basic chemical processes of the body are manifested in the interaction of acid and alkali,
which occur in a changing rhythm in the human body. A person with a normal blood pH level of 7.35 is an alkaline living being.
What is “pH level” anyway?
This important measuring number forms the basis of the acid-base balance, which has
crucial not only for nature, but also for the basic regulation of human life. Acid-base balance, regulates breathing, blood circulation, digestion, excretory processes, immunity,
hormone production and much more. Almost all biological processes proceed correctly only when
when a certain pH level is maintained.
The acid-base balance is constantly maintained in the body, in all cells of the body. In each of these cells, during their life, during the production of energy, carbon dioxide is constantly formed. At the same time, other acids appear that enter the body and are formed in it when food is consumed, bad habits, stress and anxiety.
There is a pH scale that can be used to determine how acidic or alkaline something is.
is any solution, including any physiological fluid - blood, saliva or urine.
We all know the chemical formula of water – H2O. Those who have not completely forgotten chemistry remember that if we look at the structure of this formula, we will see the following picture: H-OH, where H is a positively charged ion, and the OH group is a negatively charged ion.
Thus, we see in the composition of water there is not only an “acidic” hydrogen ion, but also an “alkaline” compound of a hydrogen atom with an oxygen atom, which create a stable bond called a “hydroxyl group”.
Thus, the formula of water is represented by two ions, which are present here in equal amounts
quantity - one negative and one positive, as a result of which we have chemically
neutral substance. Point 7 of the pH scale is precisely this indicator of neutrality. That is, this is the pH indicator of distilled (pure) water.
In general, the pH scale is divided from 0 to 14.
At pH 0, we are dealing with the highest concentration of positively charged hydrogen ions and almost zero concentration of negative OH ions, while at pH14, hydrogen ions are almost never found, and the index of OH ions reaches its maximum.
Thus, below pH 7, simple hydrogen cations (+ H) predominate. Above pH 7, hydroxyl group anions (-OH) predominate.
The lower the pH value from mark 7 to 0, the more acidic the liquid is, and vice versa, the higher the pH value from mark 7 to mark 14, the greater the manifestation of alkalinity. The number of hydrogen ions always determines the concentration or the so-called degree of acid, i.e. The more simple hydrogen ions, the more acidic the liquid. This is why the abbreviation pH comes from the Latin Potentia Hydrogenii, meaning “the power of hydrogen.” To put it in a language that is more understandable to ordinary people, this is simply an indicator of the power (concentration) of the acid. The strength of acidity decreases from 1 to 7, and then comes the domain of alkali.
A logarithmic sequence of values is hidden in the pH level measuring scale from 0 to 14.
This means, for example, that a pH value of 6 indicates an acid strength ten times greater than a pH value of 7, and a pH of 5 is already a hundred times greater than a pH of 7, and a pH of 4 is already a thousand times greater than a pH of 7.
The basis of our life - our blood - has a pH value from 7.35 to 7.45, that is, it is slightly alkaline.
Acids and alkalis are in a very close relationship in the body.
They must be in balance, with a slight preponderance on the alkaline side, since we humans belong to the “alkaline caste of the kingdom of nature.”
The vitality and health of a person depends on regularly drinking a sufficient amount of high-quality water and alkaline compounds - minerals and trace elements, otherwise the normal pH level of the blood would not be in the indicated vital range of 7.35 - 7.45.
This zone can be disturbed only slightly, otherwise a critical, life-threatening condition may occur. To prevent strong fluctuations in this pH value, the human metabolism has various buffer systems. One of them is the hemoglobin buffer system. It immediately decreases if, for example, anemia occurs or microcirculation is disrupted at the cellular level, when clumped clusters of red blood cells are unable to penetrate the capillaries and bring the cells a sufficient amount of oxygen to normalize energy metabolic processes in them and remove carbon dioxide from them ( CO2).
The reason for the formation of sludge (sticking together) of red blood cells is essentially two reasons - a chronic lack of water in the body (constant lack of drinking, thirst) and acidic foods, including all kinds of drinks that carry an excess of positively charged ions, removing the vital negative potential from the outside of the shell red blood cells (charge neutralization). Since metabolic processes between the internal and external environments in cells occur due to the difference in electrical potentials (minus outside, plus inside), the aggression of positively charged ions sharply reduces the vitality of cells (in particular red blood cells, all leukocytes and other cells). Cells moving freely in the blood, having lost vital energy, begin to precipitate and clump together, forming huge “nets”, among which leukocytes lie “lifeless”, ceasing to perform their protective (immune) functions.
In parallel with this, the functioning of all excretory organs and systems deteriorates. Increasing acidosis is inhibited by the body using a second buffer system. Acids are neutralized by alkaline earth metals and other minerals. Potassium, sodium, magnesium, and calcium replace hydrogen in acids and form neutral salts. The resulting salts should be excreted through the kidneys, but as a result of blood overoxidation, sludge and impaired microcirculation, they are not completely eliminated and are stored inside the body and, above all, inside the connective, least differentiated tissue, which is subject to the greatest destruction. The more acidified the blood becomes, the fewer salts can be dissolved in it and, accordingly, the greater their amount is deposited throughout the body.
Against the background of tissue hypoxia, acidosis and constant loss of minerals, free radicals are “activated”. The body cannot cope with their “destruction” on its own, and they turn on “nuclear reactions” of cell disintegration, causing irreparable damage to them. Under an electron microscope, sick people can detect a huge number of red blood cells “bitten” by free radicals, resembling clock gears. The number of such red blood cells can reach up to 50%. It is clear that this situation aggravates the general condition of a person and brings it to critical condition.
The main components of metabolism (homeostasis) are water, electrolyte and acid-base balance. In a healthy person they should be in biological balance. All of them are extremely important for human health and life.
I have already written a lot of material about water balance on this site and I will not repeat myself, I will only say that chronic lack of drinking clean water (involuntary chronic dehydration) is the background against which metabolic processes take place. It is chronic thirst that contributes to the increase in tissue acidosis, coupled with which, the nutritional intake of acid-forming foods destroys minerals necessary for life and activates free radicals. Essentially, involuntary chronic dehydration is the trigger for the appearance of all kinds of symptoms caused by a malfunction of two other parts of homeostasis.
Restoring a disturbed metabolism is impossible without correcting its basic functions (links). For the concept of health, understanding the importance of good water is paramount!
It is the quality and required volume of drinking water that ensures the normal course of biochemical reactions. The quality of water depends on its pH, oxidation-reduction potential (ORP) and, of course, on its hardness and mineral composition. I don’t want to list a bunch of negative factors that make water unacceptable for drinking, since we are talking about filtered, pure spring or artesian water.
Since as a result of poor nutrition, many different acids are often formed in the body, which can cause burns to tissues (cells), it is necessary to neutralize them with the help of alkaline drinking or free mineral ions supplied with food or water. Unfortunately, this most often does not happen and the acids begin to “gut” the tissues, pulling out minerals from them to replace hydrogen in the acids.
Neutral salts are formed and the level of blood acidity decreases. Hard water usually contains a lot of calcium and magnesium salts, which, when entering the body, aggravate the human condition due to the already high concentration of salts formed during the neutralization of acids. Hard water increases the amount of toxins, especially in people who constantly consume acid-forming foods. Osteoporosis is largely a consequence of calcium loss due to the high acidity of body fluids. Calcium released from the bones actively neutralizes acids, forming salts and clogging the kidneys with them (urolithiasis) and at the same time, when its molecular bonds are broken, it gives the body additional energy.
Of great importance for the fight against acidosis, in addition to correct thinking regarding your diet and reducing the intake of acid-forming foods into the body, is the functional state of the kidneys and lungs. The lion's share of all acids and salts (metabolites) dissolved in the blood and filtered through them is excreted through the kidneys, and through the lungs, thanks to gas exchange, volatile gaseous toxins are released before they have yet formed toxic acids, in particular carbon dioxide (in essence, this is almost ready-made carbon dioxide).
Poor kidney function, pulmonary pathology and smog in the surrounding atmosphere themselves cause acidosis. If we add to this all of the above, it becomes clear how difficult it is for the body to resist the endogenous acid threat, which is rapidly burning the health and life of a particular person.
A kind of vicious circle arises when a violation of metabolic processes leads to acidosis, acidosis affects the excretory organs, gradually limiting their functions, which in turn aggravates acid processes in the body, which continue to have an even more severe impact on the activity of internal organs and systems. All this contributes to further disruption of metabolic processes in a living cell (disturbance in the production of enzymes) and the production of hormones in the endocrine glands, which in turn leads to very serious consequences. One link of violations leads to another, and in order to break this vicious circle, a person must make certain efforts to orient himself in the right direction, to begin to act, without turning his restructuring into a short-term action. Actions aimed at changing the situation towards health must be reasonable, systematic and constant. This is the only way a person can get out of a difficult situation.
The longer symptomatic treatment is applied to an organism damaged as a result of dehydration and acidosis, the faster healthy cells suffocate and die prematurely from continuously accumulating toxins and wastes. Any medications prescribed by doctors or taken at your own risk only increase cell oppression. And the stress and fears of illness experienced by such people finally finish them off. Lack of energy, weakness, laziness and apathy lead to depression. Chronic fatigue syndrome, which doctors give us as a diagnosis, is a consequence of a state of chronic dehydration and acidosis.
There can only be one way out here. Understand what is happening to you by carefully studying what is written about not only in this article but also in other materials on this blog and begin to implement simple but vital recommendations. Don't get me wrong, few doctors can guide you on the right path. At best, while prescribing medications, you may be advised to drink water, but even then they will not tell you how to do it.
I know how to solve the main components of metabolism (homeostasis). Water, electrolyte and acid-base balances can be easily adjusted using portable structurers - alkaline energy glasses - ionizers.
You can get to know them . By the way For the Day of Knowledge, I am planning an unprecedented promotion, thanks to which you will be able to get structurers at a magical price, along with gifts that, without any doubt, will greatly delight you.
The quantity of goods in stock is small, so in order to take advantage of the favorable situation, I recommend signing up for the preliminary list of potential customers.
Call me at the phone number listed on the main page in the upper right corner of this site. Or register in writing by clicking on the picture below. You will be the first to be notified about the start of the promotion.
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With best regards, your Doctor BIS
PS: Don't waste days so you don't waste years. Real maintenance and regulation of the internal environment is almost free. You will always be able to control your internal environment even if you are not too dependent on nutrition. Don't miss your chance to get a structurer at a discount and great gifts.
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| In a broad sense, the concept of “physicochemical properties” of an organism includes the entire set of components of the internal environment, their connections with each other, with the cellular contents and with the external environment. In relation to the objectives of this monograph, it seemed appropriate to select physicochemical parameters of the internal environment that are of vital importance, well “homeostasis” and at the same time relatively fully studied from the point of view of specific physiological mechanisms that ensure the preservation of their homeostatic boundaries. The gas composition, acid-base state and osmotic properties of blood were selected as such parameters. Essentially, the body does not have separate isolated systems for homeostasis of these parameters of the internal environment. |
Acid-base homeostasis
Acid-base balance is one of the most important physical and chemical parameters of the internal environment of the body. The ratio of hydrogen and hydroxyl ions in the internal environment of the body largely determines the activity of enzymes, the direction and intensity of redox reactions, the processes of breakdown and synthesis of protein, glycolysis and oxidation of carbohydrates and fats, the functions of a number of organs, the sensitivity of receptors to mediators, the permeability of membranes and etc. The activity of the reaction of the environment determines the ability of hemoglobin to bind oxygen and release it to tissues. When the reaction of the environment changes, the physicochemical characteristics of cell colloids and intercellular structures change - the degree of their dispersity, hydrophilia, adsorption ability and other important properties.
The ratio of active masses of hydrogen and hydroxyl ions in biological media depends on the content of acids (proton donors) and buffer bases (proton acceptors) in body fluids. It is customary to evaluate the active reaction of the environment by one of the ions (H +) or (OH -), more often by the H + ion. The H+ content in the body is determined, on the one hand, by their direct or indirect formation through carbon dioxide during the metabolism of proteins, fats and carbohydrates, and on the other hand, by their entry into the body or removal from it in the form of non-volatile acids or carbon dioxide. Even relatively small changes in cH + inevitably lead to disruption of physiological processes, and when shifts beyond certain limits lead to the death of the organism. In this regard, the pH value, which characterizes the state of acid-base balance, is one of the most “hard” blood parameters and varies within a narrow range in humans - from 7.32 to 7.45. A pH shift of 0.1 beyond the specified limits causes pronounced disturbances in the respiratory, cardiovascular system, etc.; a decrease in pH by 0.3 causes an acidotic coma, and a shift in pH by 0.4 is often incompatible with life.
The exchange of acids and bases in the body is closely related to the exchange of water and electrolytes. All these types of exchange are united by the laws of electroneutrality, isosmolarity and homestatic physiological mechanisms. For plasma, the law of electrical neutrality can be illustrated by the data in Table. 20.
| Table 20. Plasma ion concentration (Hermann N., Cier J., 1969) | |||||
| Cations | Concentration | Anions | Concentration | ||
| mg/l | mmol/l | mg/l | mmol/l | ||
| Na+ | 3 300 | 142 | C1 - | 3650 | 103 |
| K+ | 180-190 | 5 | NSO - 3 | 1650 | 27 |
| Ca 2+ | 100 | 2,5 | Squirrels | 70000 | 7,5-9 |
| Mg 2+ | 18-20 | 0,5 | PO 2- 4 | 95-106 | 1,5 |
| SO 2- 4 | 45 | 0,5 | |||
| Other items | Approximately 1.5 | Organic acids | Approximately 5 | ||
| Total. . . | 155 mmol/l | Total. . . | 155 mmol/l | ||
The total amount of plasma cations is 155 mmol/l, of which 142 mmol/l is sodium. The total amount of anions is also 155 mmol/l, of which 103 mmol/l is the weak base C1 - and 27 mmol/l is the share of HCO - 3 (strong base). G. Ruth (1978) believes that HCO - 3 and protein anions (approximately 42 mmol/l) constitute the main buffer bases of plasma. Due to the fact that the concentration of hydrogen ions in plasma is only 40·10 -6 mmol/l, blood is a well-buffered solution and has a slightly alkaline reaction. Protein anions, especially the HCO - 3 ion, are closely related, on the one hand, to the exchange of electrolytes, and on the other, to the acid-base balance, therefore the correct interpretation of changes in their concentration is important for understanding the processes occurring in the exchange of electrolytes, water and H + .
Acid-base balance is maintained by powerful homeostatic mechanisms. These mechanisms are based on the peculiarities of the physical and chemical properties of blood and physiological processes in which the external respiration systems, kidneys, liver, gastrointestinal tract, etc. take part.
Physicochemical homeostatic mechanisms
Buffer systems of blood and tissues. Both in conditions of normal life and when the body is exposed to extreme factors, the maintenance of acid-base homeostasis is ensured primarily by physicochemical regulatory mechanisms.
- A special place among these mechanisms is occupied by the carbonate buffer system [show]
According to the law of electrolytic dissociation, the ratio of the product of the concentration of ions to the concentration of undissociated molecules is a constant value:
(H+) (HCO - 3) (H2CO3) (Na+) (HCO - 3) (NaHCO 3) The HCO - 3 ion is common to each component of the system, and therefore this ion, formed from the strongly dissociating salt NaHCO 3, will suppress the formation of a similar ion from the weak H 2 CO 3, i.e., almost all of the HCO - 3 in the bicarbonate buffer occurs from the dissociation of NaHCO 3. Therefore, equation (1) can be represented as follows:
(H+) (NaHCO3) (H2CO3) and according to the proposal of Sörensen, pH = -log (H +) is adopted as a symbol to denote an active reaction. In its final form, the Henderson-Hasselbalch equation for a carbonate buffer is usually presented as follows:
H2CO3 NaHCO3 where pK = -logK. Consequently, the carbonate buffer consists of weak H 2 CO 3 and the sodium salt of its anion (strong base HCO - 3 -NaHCO 3. Under normal conditions, there is 20 times more bicarbonate in the plasma than carbonic acid. When this buffer comes into contact with acids, the latter are neutralized by alkaline component of the buffer with the formation of weak H 2 CO 3. The carbon dioxide then formed excites the respiratory center, and all excess carbon dioxide is removed from the blood with exhaled air. The carbonate buffer is also able to neutralize excess bases that will be bound by carbon dioxide with the formation of NaHCO 3 and its subsequent release kidneys.
The buffer capacity of the carbonate system is 7-9% of the total buffer capacity of the blood, but its importance is very great due to the fact that it is closely related to other buffer systems and its condition also depends on the functions involved in maintaining the acid-base homeostasis of the excretory organs. Thus, it is a sensitive indicator of acid-base balance and the determination of its components is widely used to diagnose its disorders.
- Another plasma buffer system is the phosphate buffer, formed by mono- and dibasic phosphate salts [show]
:
Phosphate buffer formed by mono- and dibasic phosphate salts:
NaH2PO4 1 Na2PO4 4 Monobasic phosphorus salts are weak acids, while dibasic salts have a clearly expressed alkaline reaction. The principle of operation of a phosphate buffer is similar to that of a carbonate buffer. The direct role of the phosphate buffer in the blood is insignificant; this buffer is of much greater importance in the renal regulation of acid-base homeostasis. It also plays a significant role in regulating the active reaction of certain tissues. In the blood, its action mainly comes down to maintaining the constancy and reproduction of the bicarbonate buffer. In fact, the “aggression” of acids causes an increase in the H 2 CO 3 content and a decrease in the NaHCO 3 content in a system containing carbonate and phosphate buffers. Due to the simultaneous presence of a phosphate buffer in the solution, an exchange reaction occurs:
i.e., excess H 2 CO 3 is eliminated, and the concentration of NaHCO 3 increases, maintaining a constant expression:
H2CO3 1 NaHCO3 20 - The third buffer system of the blood is proteins [show]
The buffering properties of proteins are determined by their amphotericity. Proteins can dissociate to form both H + and OH - ions. The nature of dissociation depends on the chemical nature of the protein and the reaction of the environment. The buffering capacity of plasma proteins is small compared to bicarbonates. The largest buffering capacity of blood (up to 75%) is hemoglobin. Human hemoglobin contains 8.1% histidine, an amino acid that includes both acidic (COOH) and basic (NH 2) groups. The buffering properties of hemoglobin are due to the possibility of interaction of acids with the potassium salt of hemoglobin to form an equivalent amount of the corresponding potassium salt and free hemoglobin, which has the properties of a very weak organic acid. In this way, very significant amounts of H + ions can bind. The ability to bind H + ions is more pronounced in hemoglobin salts than in oxyhemoglobin salts (HbO 2), i.e. Hb is a weaker organic acid than HbO 2. Therefore, when HbO 2 dissociates in tissue capillaries into O 2 and Hb, an additional amount of bases (alkaline-reactive hemoglobin salts) appears that can bind carbon dioxide, counteracting the decrease in pH. On the contrary, oxygenation of hemoglobin leads to the displacement of H 2 CO 2 from bicarbonate (Fig. 38).
These mechanisms, obviously, can come into play not only during the conversion of arterial blood into venous blood and vice versa, but also in all those cases when Pco 2 changes. Hemoglobin is also capable of binding carbon dioxide using free amino groups, forming carbhemoglobin:
Thus, the consumption of NaHCO 3 bicarbonate in the carbonate buffer system during acid “aggression” is compensated by alkaline proteinates, phosphates and hemoglobin salts.
The exchange of Cl - and HCO - 3 ions between red blood cells and plasma is also extremely important. When the concentration of carbon dioxide in plasma increases, the concentration of Cl - in it decreases, since Cl - passes into red blood cells. The main source of Cl - in plasma is sodium chloride; therefore, an increase in the concentration of carbonic acid causes a break in the bond between Na + and Cl - and their separation, with Cl - entering the erythrocytes, and Na + remaining in the plasma, since the erythrocyte membrane is practically impermeable to them. The resulting excess Na + combines with excess HCO - 3, forming sodium bicarbonate, replenishing its loss resulting from acidification of the blood, and thereby maintaining a constant blood pH.
A decrease in Pco 2 causes the reverse process: Cl - leaves the red blood cells, combining with excess Na + released from bicarbonate, and thereby preventing alkalization of the blood. These movements of ions through the semi-permeable membrane of erythrocytes are explained by one of Donnan’s rules, which states that the ratios of the concentrations of ions capable of passing through the membrane must be equal on both sides of the membrane. This process is of utmost importance for maintaining blood pH, Cl - er / Cl - pl = 0.48-0.52 can serve as one of the indicators of the state of acid-base homeostasis.
A major role in maintaining acid-base homeostasis belongs to tissue buffer systems, which maintain the constancy of interstitial pH and are involved in the regulation of blood pH. Tissues contain carbonate and phosphate buffer systems. However, a special role is played by tissue proteins, which are capable of binding very large amounts of acids and alkalis. The most pronounced buffer capacity is in the collagen substance of connective tissue, which is also capable of binding acids through their adsorption.
Homeostatic metabolic processes. A very significant role in the regulation of acid-base balance is played by metabolic processes occurring in tissues, especially in the liver, kidneys, and muscles. Organic acids can undergo oxidation with the formation of either volatile acids that are easily released from the body (mainly carbon dioxide), or turning into non-acidic substances. They can combine with products of protein metabolism, completely or partially losing their acidic properties (for example, the combination of benzoic acid with glycine); lactic acid, formed in large quantities during intense muscular work, is resynthesized into glycogen, ketone bodies - into higher fatty acids and then into fats, etc. Inorganic acids can be neutralized by potassium and sodium salts, released when amino acids are deaminated with ammonia to form ammonium acids salts, etc. Alkalis are neutralized mainly by lactic acid, which, when the active reaction of tissues shifts to the alkaline side, is intensively formed from glycogen. Acid-base homeostasis is also supported by a number of physicochemical processes: the dissolution of strong acids and alkalis in media with a low dielectric constant (for example, in lipids), the binding of acids and alkalis by various organic substances into undissociated and insoluble salts, the exchange of ions between cells of various tissues and blood, etc.
Noting the importance of the mechanisms discussed above for maintaining acid-base homeostasis, it should be recognized that ultimately the key link in the homeostatic system under consideration is cellular metabolism, since the movement of anions and cations between extra- and intracellular sectors and their distribution in these sectors are primarily the result cell activity and are subject to the needs of this activity.
The mechanisms that ensure this exchange are very diverse. The movement of ions depends on the osmotic pressure gradient, membrane permeability, and is determined by the dynamic electrical potential of membranes, etc.
Physiological homeostatic mechanisms
The second echelon of maintaining acid-base homeostasis is represented by physiological regulatory mechanisms, among which the main role belongs to the lungs and kidneys.
Thanks to blood buffers, organic acids formed during the metabolic process, or acids introduced into the body from the outside, do not change the blood reaction, but only displace carbon dioxide from its connection with bases; Excess carbon dioxide is eliminated by the lungs. The high diffusion capacity of carbon dioxide ensures the rapid passage of gas through membranes and its removal from the body. The rate of diffusion of any gas is inversely proportional to the square root of its molecular weight, and the amount of gas diffusing is proportional to its solubility in the liquid.
Combining these two laws of diffusion allows us to conclude that carbon dioxide diffuses approximately 20 times more intensely than oxygen:
where 0.545 and 0.023 are the solubility coefficients of CO 2 and O 2, respectively, in water at t=38°C. The transition of carbon dioxide from the blood to the alveolar air is explained by the Pco 2 gradient present here. This process is facilitated by two mechanisms: the transition of Hb to HbO 2, which displaces carbon dioxide as a stronger acid from the blood, and the action of carbonic anhydrase, which plays a large role in the release of free carbon dioxide in the lungs. The amount of carbon dioxide removed from the lungs depends primarily on the amplitude and frequency of respiratory movements. Breathing parameters are regulated depending on the carbon dioxide content in the body. In general, the relationship between Pco 2 in the blood and pulmonary ventilation is expressed as follows (Ruth G., 1978):
where Pco 2 and P (barometric pressure) are expressed in millimeters of mercury, CO 2 production is in moles, and alveolar ventilation is in liters.
The role of the kidneys in maintaining acid-base homeostasis is determined mainly by their acid-excretory function. Under physiological conditions, the kidneys produce acidic urine, the pH of which ranges from 5.0 to 7.0. The pH value of urine can reach 4.5, and, consequently, the concentration of free H + ions can be 800 times higher than their content in the blood plasma. Acidification of urine in the proximal and distal tubules is the result of the secretion of H + ions, in the formation and secretion of which (acidogenesis) the enzyme carbonic anhydrase (CA), contained in the cells of the tubules, plays an important role. The enzyme accelerates the achievement of equilibrium between the slow reaction of hydration and dehydration of carbonic acid (H 2 CO 3):
The rate of this uncatalyzed reaction increases as pH decreases. Acidogenesis ensures the removal of acidic components of the phosphate buffer (during the formation of acidic urine, the following transformation occurs: HPO 2- 4 + H + ---> H 2 PO 4), as well as weak organic acids: lactic, citric, β-hydroxybutyric, etc. The process The release of H + by the epithelium of the renal tubules occurs against an electrochemical gradient with the expenditure of a large amount of energy and requires simultaneous reabsorption of an equivalent amount of Na + ions. A decrease in sodium reabsorption is usually accompanied by a decrease in acidogenesis. Reabsorbed as a result of acidogenesis, Na + forms in the blood, together with HCO - 3 secreted from the epithelium of the renal tubules, sodium bicarbonate. H + ions secreted by renal tubular cells interact with the anions of buffer compounds. Acidogenesis ensures the release of predominantly anions of carbonate and phosphate buffers, as well as anions of weak organic acids.
When filtering compounds containing anions of strong organic and inorganic acids (Cl - , SO 2- 4), another mechanism is activated in the kidneys - ammoniogenesis, which ensures the excretion of acids and protects against a decrease in urine pH below a critical level (Fig. 39). Ammoniogenesis occurs at the level of the distal tubules and collecting ducts. NH 3 formed in the epithelium of the renal tubules enters the lumen of the tubules, where it interacts with H + resulting from acidogenesis. Thus, NH3 ensures, on the one hand, the binding of H +, and on the other, the removal of strong acid anions in the form of ammonium salts, in which H + ions do not have a damaging effect on the tubular epithelium. The source of ammonium is mainly blood glutamine. About 60% of NH 3 is formed from glutamine by its deamination with iodine by the action of the enzyme glutaminase I. The remaining 40% of ammonia is formed from other amino acids (Pitts R. F., 1964)
Since ammoniogenesis is closely related to acidogenesis, it is obvious that the concentration of ammonium in the urine is directly dependent on the concentration of H + in it. Blood acidification, leading to a decrease in the pH of the tubular fluid, promotes the diffusion of ammonia from the cells. The intensity of ammonium excretion is also determined by the rate of its production and the rate of urine flow, which determines the time of contact between the tubular fluid and the epithelium of the renal tubule, and, consequently, the timely removal of the resulting ion from the cell.
Chlorides play an important role in the regulation of acid excretion by the kidneys. In particular, an increase in HCO-3 reabsorption is usually accompanied by an increase in chloride reabsorption. The C1- ion generally passively follows the Na+ cation. An increase in the concentration of HCO - 3 bicarbonates in the urine is usually accompanied by a decrease in the content of chlorides in such a way that the sum of these anions is equivalent to the amount of Na + (Matthews D. L., O'Connor W. J., 1968). The change in chloride transport is a consequence of a primary change in the secretion of H + ions and bicarbonate reabsorption and is due to the need to maintain electrical neutrality of tubular urine. According to another point of view, the transport of chlorides changes primarily.
In addition to the mechanisms of acidogenesis and ammoniogenesis, the secretion of K + ions plays a significant role in the preservation of the Na + ion during blood acidification. Potassium, released from cells when blood pH decreases, is excreted by the renal tubules in increased quantities; at the same time, increased reabsorption of Na + occurs. This metabolism is regulated by mineralocorticoids (aldosterone, deoxycorticosterone). Under normal conditions, the kidneys secrete predominantly acidic metabolic products. With an increase in the intake of bases into the body, the urine reaction becomes more alkaline due to increased excretion of bicarbonate and basic phosphate.
The gastrointestinal tract occupies a certain place in the excretory regulation of acid-base homeostasis. Cells of the gastric mucosa secrete HCl, which is formed from Cl - ions coming from the blood and H + ions originating from the gastric epithelium. In exchange for chlorides, bicarbonate enters the blood through gastric secretion. Alkalinization of the blood, however, does not occur, since the Cl ions of gastric juice are reabsorbed into the blood in the intestines. The epithelium of the intestinal mucosa secretes alkaline juice rich in bicarbonates. In this case, H + ions pass into the blood in the form of HC1. The short-term shift in the reaction is immediately balanced by the reabsorption of bicarbonate in the intestine. While the kidneys concentrate and excrete primarily H+ and monovalent cations from the body, the intestinal tract concentrates and excretes divalent alkaline ions. With an acidic diet, the release of mainly divalent Ca 2+ and Mg 2+ increases, with an alkaline diet - the release of all cations.
Acid-base balance disorders
The homeostatic acid-base balance system by its nature is incapable of continuously being in a state of tension for a long time in the presence of disturbing influences. Disorders of acid-base homeostasis can arise as a result of long-term continuous action of even moderately intense disturbing factors or if the influence of disturbing factors is short-term, but their intensity goes beyond the capabilities of urgently mobilized homeostatic mechanisms. Absolute or relative insufficiency of homeostatic mechanisms (or their reserve capabilities) can become the basis for disturbances in the acid-base balance of the internal environment of the body and lead to acidosis or alkalosis.Currently, acidosis is a violation of the acid-base balance in which a relative or absolute excess of acids appears in the blood. Alkalosis is characterized by an absolute or relative increase in the amount of bases in the blood. According to the degree of compensation, all acidoses and alkaloses are divided into compensated and uncompensated. Compensated acidosis and alkalosis are also conditions when the absolute amounts of H 2 CO 3 and NaHCO 3 change, but the NaHCO 3 /H 2 CO 3 ratio remains within normal limits (about 20:1). If the specified ratio is maintained, the pH of the blood does not change significantly. Accordingly, uncompensated acidosis and alkalosis are conditions when not only the total amount of H 2 CO 3 and NaHCO 3 changes, but also their ratio, resulting in a shift in blood pH in one direction or another (Weisberg N. F., 1977).
The concepts of “non-gas acidosis” and “metabolic acidosis” (or alkalosis) are used as synonyms. However, such an identification of terms cannot be considered justified. Non-gas acidosis (alkalosis) is a collective concept that includes all possible forms of disturbances in acid-base homeostasis, leading to a primary change in the content of blood bicarbonate, i.e., the denominator of the fraction in the equation:
| H2CO3 | |||
| NaHCO3 |
The development of non-gas acidosis may be due to:
- an increase in the supply of acids from the outside;
- metabolic disorders accompanied by the accumulation of organic acids, the inability of the kidneys to remove acids, or, conversely, excessive excretion of buffer bases through the kidneys and gastrointestinal tract.
Consequently, only those acidoses that develop as a result of metabolic disorders leading to excessive accumulation of acids can be called metabolic acidoses in the strict sense of the word. Acidoses caused by difficulty in removing acids from the body or excessive loss of buffer anions should be classified as excretory acidoses.
Based on the above considerations, the classification of acid-base balance disorders can be presented in the form of the following diagram.
- Gas-respiratory (accumulation of carbon dioxide):
- difficulty in removing carbon dioxide due to breathing problems;
- high concentration of carbon dioxide in the environment (closed spaces, mines, submarines, etc.);
- malfunctions of anesthesia-respiratory equipment (rare!).
- Non-gas (accumulation of non-volatile acids):
- Metabolic:
- ketoacidosis due to increased production or impaired oxidation and resynthesis of ketone bodies (diabetes mellitus, fasting, liver dysfunction, fever, hypoxia, etc.)
- lactic acidosis due to increased production, decreased oxidation and resynthesis of lactic acid (hypoxia, impaired liver function, infections, etc.);
- acidosis due to the accumulation of other organic and inorganic acids (extensive inflammatory processes, burns, injuries, etc.).
- Excretory:
- acid retention in renal failure (diffuse nephritis, uremia);
- loss of alkalis, renal (renal tubular acidosis, desalting nephritis, hypoxia, sulfonamide intoxication); loss of alkalis, gastroenteric (diarrhea, hypersalivation)
- Exogenous:
- prolonged consumption of acidic foods;
- taking medications (NH 4 Cl);
- taking acids orally (rarely!)
- Combined forms:
- ketoacidosis + lactic acidosis;
- metabolic + excretory;
- various other combinations.
- Metabolic:
- Mixed (gas + non-gas) for asphyxia, cardiovascular failure, severe conditions with disorders of the cardiovascular and respiratory systems, etc.).
- Gas-breathing:
- increased removal of carbon dioxide during external respiration disorders of a hyperventilation nature;
- hyperventilation controlled breathing
- Non-gas:
- Excretory:
- alkali retention (increased reabsorption of alkaline anions (bases) by the kidneys);
- loss of acids (vomiting due to pyloric stenosis, intestinal obstruction, toxicosis of pregnancy; hypersecretion of gastric juice);
- hypochloremic-"metabolic"
- Exogenous:
- long-term intake of alkaline foods;
- administration of drugs (bicarbonate and other alkaline substances)
- Excretory:
MIXED FORMS OF ACIDOSES AND ALKALOSES (EXAMPLES)
- Gas alkalosis + metabolic acidosis (altitude sickness, blood loss);
- Gas alkalosis + renal tubular acidosis (heart failure and treatment with carbonic anhydride inhibitors);
- Arterial gas alkalosis + venous gas acidosis (breathing pure oxygen under high pressure), etc.
Homeostatic processes in acidosis and alkalosis and their disorders. With the development of acidosis, the following changes occur in buffer systems and regulatory mechanisms. If acidosis is caused by an excess of any strong acid, for example, HC1, then the following reactions will occur:
- HC1 + NaHCO 3 H 2 CO 3 + NaCl.
Hence,
i.e., some excess of H 2 CO 3 and some deficiency of NaHCO 3 arise.
- Excess H 2 CO 3 (H + and CO 2) causes increased activity of the respiratory center, which leads to hyperventilation and leaching of CO 2 from the blood.
- Excess H 2 CO 3 NaHCO 3 + NaH 2 PO 4. This reaction provides, to some extent, the elimination of NaHCO 3 deficiency.
- NaHCO 3 is replenished to a large extent due to the exchange of ions between erythrocytes and plasma according to Donnan’s rule, i.e. C1 - ions enter erythrocytes, creating an excess of Na + ions in the plasma, which, combining with excess HCO - 3, form bicarbonate.
- HCl + Na 2 HPO 4 = NaH 2 PO 4 + NaCl, i.e. the acid is partially neutralized with basic phosphates.
- Acid is excreted by the kidneys in the form of Na + and K + salts or in the form of ammonium salts. The inclusion of these mechanisms provides compensation for the resulting acidosis, which can turn into an uncompensated form if buffer systems are depleted or there is a failure of excretory processes.
The most common forms of acidosis are:
Metabolic acidosis, resulting from the accumulation of intermediate acidic metabolic products, such as ketone bodies (acetoacetic, β-hydroxybutyric acids), lactic acid and other organic acids. Hyperketonemia can develop as a result of increased production of ketone bodies, for example, with a decrease in glycogen content in the liver, as well as with intensive breakdown of fats; in case of violations of the tricarboxylic acid cycle, leading to inhibition of the oxidation of ketone bodies; with oxygen starvation, decreased production of NADP and inhibition of their resynthesis. Often there is a combined effect of several factors causing hyperketonemia (for example, in pancreatic diabetes). The concentration of ketone bodies under pathological conditions can increase tens and hundreds of times. Significant amounts of ketone bodies are excreted by the kidneys in the form of sodium and potassium salts, which can lead to large losses of alkaline ions and the development of uncompensated acidosis. This condition occurs with diabetes mellitus, fasting (especially carbohydrate fasting), high fever, severe insulin hypoglycemia, and with certain types of anesthesia.
Acidosis due to the accumulation of lactic acid is quite common, even in healthy people. Short-term acidosis occurs during intense muscle work, especially in untrained people, when the concentration of lactic acid increases due to a relative lack of oxygen. Long-term acidosis of this kind occurs with severe liver damage (cirrhosis, toxic dystrophies), with decompensation of cardiac activity, as well as with a decrease in the supply of oxygen to the body associated with insufficient external respiration, and with other forms of oxygen starvation.
Non-gas excretory acidosis due to a decrease in the release of non-volatile acids is observed in kidney diseases, when the release of acid phosphates, sulfates, and organic acids is difficult, ammoniaogenesis is inhibited, while buffer bases are released more or less normally. As a result, acidosis may occur due to a relative or absolute excess of H +. Such acidosis occurs in chronic diffuse glomerulonephritis, nephrosclerosis and some other severe kidney damage. The decompensated form is usually observed with uremia. Increased excretion of bicarbonate in the urine occurs with some intoxications, for example, with prolonged use of sulfonamides, which inhibit the activity of carbonic anhydrase and lead to a weakening of acidogenesis. Acidosis in nephritis develops as a consequence of primary insufficiency of excretion of organic acids in the urine in free form and in the form of ammonium salts. At the same time, it has been shown that the reabsorption of bicarbonate in the kidneys when they are damaged is reduced. The reaction of urine in renal acidosis is usually neutral or alkaline. Compensation for acidosis against the background of kidney damage can only be achieved through the mobilization of a large number of cations and, above all, sodium from all its compounds. A significant sodium reserve in this case is the skeletal system. Non-gas acidosis can also develop with increased secretion of alkalis through the gastrointestinal tract, for example, with diarrhea in children or with vomiting of alkaline intestinal juice.
Gas acidosis is characterized by the accumulation of carbonic acid in the blood as a result of insufficient external respiration function or due to the presence of more or less significant amounts of carbon dioxide in the inspired air.
The possibility of developing mixed forms of acidosis is based, in particular, on the fact that the exchange of carbon dioxide in the lungs is approximately 25 times more intense than the exchange of oxygen. Therefore, whenever the release of carbon dioxide is difficult due to damage to the lungs or heart, oxygen starvation develops with the subsequent accumulation of under-oxidized products of interstitial metabolism. Moderate compensated acidosis occurs without pronounced clinical symptoms and is recognized by examining the blood buffer systems, as well as the composition of urine. As acidosis deepens, one of the first clinical symptoms is increased breathing, which, with uncompensated acidosis, turns into severe shortness of breath. Uncompensated acidosis is also characterized by disorders of the cardiovascular system and gastrointestinal tract, largely due to the fact that acidosis simultaneously reduces the activity of α- and β-adrenergic receptors of the heart, blood vessels and intestines, reducing the functional and metabolic effect of catecholamines.
Acidosis leads to an increase in the content of catecholamines in the blood, therefore, in the process of its development, an increase in cardiac activity, an increase in heart rate, an increase in minute volume of blood, and an increase in blood pressure are first noted. But as acidosis deepens, the activity 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, extrasystoles and other rhythm disturbances appear, including ventricular fibrillation. It has also been established that acidosis sharply enhances parasympathetic effects, causing bronchospasm and increased secretion of the bronchial glands. From the gastrointestinal tract, vomiting and diarrhea are observed.
When there is an excess of H + in the plasma, some of it moves inside the cells in exchange for K +, which is split off from proteins in an acidic environment. In diagnostic terms, the plasma K + concentration can serve as a sign of the severity of “biochemical trauma” of body tissues. In addition, some of the HCO3 ions enter the cells and neutralize H + ions. Instead of HCO3, C1 - leaves the cells, the osmotic pressure of the extracellular fluid increases, and extracellular hyperhydria develops. With uncompensated acidosis, sharp disturbances in the function of the central nervous system occur, dizziness and drowsiness appear first, and then, with the development of acidotic coma, complete loss of consciousness occurs. Naturally, acidotic symptoms are combined with symptoms of the underlying disease that caused acidosis.
Alkalosis. With the accumulation of alkaline compounds in the body, the following fundamental changes occur in the homeostatic acid-base balance system (in the example given, NaOH is conventionally taken as an alkaline compound).
- NaOH + H 2 CO 3 NaHCO 3 + H 2 0
Hence,
H 2 CO 3 - H 2 CO 3 spent NaHCO 3 + NaHCO 3 formed i.e., a certain excess of NaHCO 3 and a deficiency of H 2 CO 3 is created.
- The deficiency of H 2 CO 3 is compensated, firstly, by the release of Cl - ions from erythrocytes and the release of HCO - 3 ions from sodium bicarbonate: Cl - + NaHCO 3 NaCl + HCO 3. (The HCO - 3 ion, together with H + leaving the cells in exchange for K + ions, forms H 2 CO 3; secondly, with a lack of H 2 CO 3, the activity of the respiratory center decreases, which leads to a decrease in ventilation and a delay in the release of carbon dioxide from the body.
- NaOH + NaH 2 PO 4 Na 2 HPO 4 + H 2 O, i.e. some of the alkali is bound by acid phosphates.
- Excess NaHCO 3 and Na 2 HPO 4 is excreted in the urine, which helps maintain pH within normal limits.
Until the buffer systems are depleted and the kidneys are functioning normally, alkalosis remains compensated, and then, if the pH-maintaining mechanisms fail, it can turn into an uncompensated form.
Non-gas alkalosis is of greatest clinical importance, in particular its gastroenteric form, which occurs when vomiting acidic gastric contents (pyloric stenosis, intestinal obstruction). In case of kidney diseases, accompanied by a loss of the ability to excrete Na + , K + cations, etc., the renal form of non-gas alkalosis develops.
Gas alkalosis is a consequence of hyperventilation that occurs during altitude sickness, hysteria, epilepsy and other conditions when increased activity of the respiratory center is not associated with exposure to carbon dioxide, as well as during excessive artificial respiration. Symptoms of alkalosis manifest themselves in weakened respiratory function and increased neuromuscular excitability, which can lead to tetany. This is due to a decrease in plasma Ca 2+ levels. At the same time, the content of Cl - in the plasma increases, the amount of ammonia in the urine decreases (inhibition of ammoniogenesis) and a shift in its reaction to the alkaline side is noted (the result of increased excretion of bicarbonates). Alkalosis increases the excitability of β-adrenergic receptors in the heart, blood vessels, intestines and bronchi, while simultaneously reducing parasympathetic effects. This is expressed in increased heart rate, accompanied by a drop in systemic blood pressure. From the gastrointestinal tract, constipation is observed due to slower peristalsis. No effect of alkalosis on α-adrenergic receptors was detected.
Mixed forms of alkalosis can be observed, for example, with brain injuries accompanied by shortness of breath (gas alkalosis) and vomiting of acidic gastric juice (non-gas alkalosis).
Combined forms of acid-base balance disorders can occur during artificial hyperventilation, leading, on the one hand, to gas alkalosis (increased leaching of carbon dioxide), and on the other, to metabolic acidosis (impaired dissociation of oxyhemoglobin in tissues during alkalosis). Similar disorders occur with altitude sickness. Disorders of the acid-base balance are not always accompanied by pronounced clinical symptoms, but gradually undermine the body’s protective capabilities, subsequently leading to irreversible disorders.
The acid-base state is one of the most important physical and chemical parameters of the internal environment of the body. In the body of a healthy person, acids are constantly formed daily during the metabolic process - about 20,000 mmol of carbonic acid (H 2 C0 3) and 80 mmol of strong acids, but the concentration of H + fluctuates in a relatively narrow range. Normally, the pH of the extracellular fluid is 7.35-7.45 (45-35 nmol/l), and the pH of the intracellular fluid is on average 6.9. At the same time, it should be noted that the H+ concentration inside the cell is heterogeneous: it is different in the organelles of the same cell.
H+ are reactive to such an extent that even a short-term change in their concentration in the cell can significantly affect the activity of enzyme systems and physiological processes; however, normally, buffer systems instantly turn on, protecting the cell from unfavorable pH fluctuations. The buffer system can bind, or, conversely, release H+ immediately in response to changes in the acidity of the intracellular fluid. Buffer systems also operate at the level of the body as a whole, but ultimately the regulation of the body’s pH is determined by the functioning of the lungs and kidneys.
So, what is the acid-base state (syn.: acid-base balance; acid-base state; acid-base balance; acid-base homeostasis)? This is the relative constancy of the pH value of the internal environment of the body, due to the combined action of buffer and some physiological systems of the body.
Acid-base balance is the relative constancy of the hydrogen index (pH) of the internal country of the body, due to the combined action of buffer and some physiological systems, which determines the usefulness of metabolic transformations in the cells of the body (Big Medical Encyclopedia, vol. 10, p. 336).
The ratio of hydrogen and hydroxyl ions in the internal environment of the body depends on:
1) enzyme activity and intensity of redox reactions;
2) processes of hydrolysis and protein synthesis, glycolysis and oxidation of carbohydrates and fats;
3) sensitivity of receptors to mediators;
4) membrane permeability;
5) the ability of hemoglobin to bind oxygen and release it to tissues;
6) physicochemical characteristics of colloids and intercellular structures: the degree of their dispersity, hydrophilia, adsorption ability;
7) functions of various organs and systems.
The ratio of H+ and OH- in biological media depends on the content of acids (proton donors) and buffer bases (proton acceptors) in body fluids. The active reaction of the medium is assessed by one of the ions (H+ or OH-), most often by H+. The H+ content in the body depends on their formation during the metabolism of proteins, fats and carbohydrates, as well as their entry into the body or removal from it in the form of non-volatile acids or carbon dioxide.
The pH value, which characterizes the state of the CBS, is one of the most “hard” blood parameters and varies in humans within very narrow limits: from 7.35 to 7.45. A pH shift of 0.1 beyond the specified limits causes pronounced disturbances in the respiratory, cardiovascular system, etc., a pH decrease of 0.3 causes acidotic coma, and a pH shift of 0.4 is often incompatible with life.
The exchange of acids and bases in the body is closely related to the exchange of water and electrolytes. All these types of metabolism are united by the law of electrical neutrality, isosmolarity and homeosgatic physiological mechanisms.
The total amount of plasma cations is 155 mmol/l (Na+ -142 mmol/l; K+ - 5 mmol/l; Ca2+ - 2.5 mmol/l; Mg2+ - 0.5 mmol/l; other elements - 1.5 mmol/l ) and the same amount of anions is contained (103 mmol/l - weak base Cl-; 27 mmol/l - strong base HC03-; 7.5-9 mmol/l - protein anions; 1.5 mmol/l - phosphate anions; 0. 5 mmol/l - sulfatanions; 5 mmol/l - organic acids). Since the H+ content in plasma does not exceed 40x106 mmol/l, and the main buffer bases of plasma HCO3- and protein anions are about 42 mmol/l, the blood is considered a well-buffered medium and has a slightly alkaline reaction.
Protein and HCO3- anions are closely related to the metabolism of electrolytes and CBS. In this regard, the correct interpretation of changes in their concentration is of decisive importance for assessing the processes occurring in the exchange of electrolytes, water and H+. CBS is supported by blood and tissue buffer systems and physiological regulatory mechanisms, which involve the lungs, kidneys, liver, and gastrointestinal tract.
Physicochemical homeostatic mechanisms
Physicochemical homeostatic mechanisms include buffer systems of blood and tissues and, in particular, the carbonate buffer system. When the body is exposed to disturbing factors (acids, alkalis), the maintenance of acid-base homeostasis is ensured, first of all, by a carbonate buffer system consisting of weak carbonic acid (H 2 CO3) and the sodium salt of its anion (NaHCO3) in a ratio of 1:20. When this buffer comes into contact with acids, the latter are neutralized by the alkaline component of the buffer with the formation of weak carbonic acid: NaHC03 + HCl > NaCl + H2C03
Carbonic acid dissociates into CO2 and H20. The resulting CO2 excites the respiratory center, and excess carbon dioxide is removed from the blood with exhaled air. The carbonate buffer is also able to neutralize excess bases by binding with carbonic acid to form NaHCO3 and its subsequent excretion by the kidneys:
NaOH + H2C03 > NaHCO + H20.
The specific gravity of the carbonate buffer is small and amounts to 7-9% of the total buffer capacity of the blood, however, this buffer occupies a central place in its importance in the blood buffer system, since it is the first to come into contact with disturbing factors and is closely connected with other buffer systems and physiological regulatory mechanisms. Therefore, the carbonate buffer system is a sensitive indicator of CBS, so the determination of its components is widely used to diagnose CBS disorders.
The second buffer system of the blood plasma is a phosphate buffer formed by monobasic (weak acids) and dibasic (strong bases) phosphate salts: NaH2P04 and Na2HP04 in a ratio of 1:4. Phosphate buffer acts similarly to carbonate buffer. The stabilizing role of phosphate buffer in the blood is insignificant; it plays a much greater role in the renal regulation of acid-base homeostasis, as well as in the regulation of the active reaction of some tissues. The phosphate buffer in the blood plays an important role in maintaining the ACR and the reproduction of the bicarbonate buffer:
H2CO3 + Na2HPO4 > NaHC03 + NaH2PO 4 i.e. excess H2C03 is eliminated, and the concentration of NaHC03 increases, and the ratio of H2C03/NaHC03 remains constant at 1:20.
The third blood buffer system is proteins, the buffering properties of which are determined by their amphotericity. They can dissociate to form both H+ and OH-. However, the buffering capacity of plasma proteins compared to bicarbonates is small. The largest buffering capacity of blood (up to 75%) is hemoglobin. Histidine, which is part of hemoglobin, contains both acidic (COOH) and basic (NH2) groups.
The buffering properties of hemoglobin are due to the possibility of interaction of acids with the potassium salt of hemoglobin to form an equivalent amount of the corresponding potassium salt and free hemoglobin, which has the properties of a very weak organic acid. Large amounts of H+ can be bound in this way. The ability to bind H+ in Hb salts is more pronounced than in oxyhemoglobin salts (HbO2). In other words, hemoglobin is a weaker organic acid than oxyhemoglobin. In this regard, during the dissociation of HbO, an additional amount of bases (Hb salts) appear in the tissue capillaries on O2 and Hb, capable of binding carbon dioxide, counteracting the decrease in pH, and vice versa, the oxygenation of Hb leads to the displacement of H2CO3 from bicarbonate. These mechanisms operate during the conversion of arterial blood into venous blood and vice versa, as well as when pCO2 changes.
Hemoglobin is able to bind carbon dioxide using free amino groups, forming carbohemoglobin
R-NH2 + CO2 - R-NHCOOH
Thus, NHC03 in the carbonate buffer system during the “aggression” of acids is compensated by alkaline proteins, phosphates and hemoglobin salts.
The exchange of Cl and HCO3 between erythrocytes and plasma is extremely important in maintaining CBS. With an increase in the concentration of carbon dioxide in the plasma, the concentration of Cl in it decreases, since chlorine ions pass into red blood cells. The main source of Cl in plasma is NaCl. As the concentration of H2CO3 increases, the bond between Na+ and Cl- breaks and their separation occurs, with chlorine ions entering the erythrocytes, and sodium ions remaining in the plasma, since the erythrocyte membrane is practically impermeable to them. At the same time, the resulting excess Na+ combines with excess HCO3-, forming sodium bicarbonate and replenishing its loss during blood acidification and thus maintaining a constant blood pH.
A decrease in pCO2 in the blood causes the opposite process: chlorine ions leave the red blood cells and combine with excess sodium ions released from NaHC03, which prevents alkalization of the blood.
An important role in maintaining CBS belongs to tissue buffer systems - they contain carbonate and phosphate buffer systems. However, a special role is played by tissue proteins, which have the ability to bind very large quantities of acids and alkalis.
An equally important role in the regulation of CBS is played by homeostatic metabolic processes occurring in tissues, especially in the liver, kidneys and muscles. Organic acids, for example, can be oxidized to form volatile acids that are easily released from the body (mainly in the form of carbon dioxide), or combine with products of protein metabolism, completely or partially losing their acidic properties.
Lactic acid, formed in large quantities during intense muscular work, can be resynthesized into glycogen, and ketone bodies into higher fatty acids, and then into fats, etc. Inorganic acids can be neutralized by potassium and sodium salts, released when amino acids are deaminated with ammonia to form ammonium salts.
Alkalies can be neutralized by lactate, which is intensively formed from glycogen when the pH of tissues shifts. CBS is maintained due to the dissolution of strong acids and alkalis in lipids, their binding by various organic substances into non-dissociable and insoluble salts, and the exchange of ions between the cells of various tissues and the blood.
Ultimately, the determining link in maintaining acid-base homeostasis is cellular metabolism, since the transmembrane flow of anions and cations and their distribution between extra- and intracellular sectors is the result of cell activity and is subject to the needs of this activity.
Physiological homeostatic mechanisms
An equally important role in maintaining acid-base homeostasis is played by physiological homeostatic mechanisms, among which the leading role belongs to the lungs and kidney.” Organic acids formed during the metabolic process, or acids that enter the body from the outside, thanks to the buffer systems of the blood, displace carbon dioxide from its compounds with bases, and the resulting excess CO2 is excreted by the lungs.
Carbon dioxide diffuses approximately 20 times more intensely than oxygen. This process is facilitated by two mechanisms:
the transition of hemoglobin to oxyhemoglobin (oxyhemoglobin, as a stronger acid, displaces CO2 from the blood);
The action of pulmonary carbonic anhydrase carbonic anhydrase
n2co3 - co2+ n2o.
The amount of carbon dioxide removed from the body by the lungs depends on the frequency and amplitude of breathing and is determined by the carbon dioxide content in the body.
The participation of the kidneys in maintaining CBS is determined mainly by their acid-excreting function. Under normal conditions, the kidneys produce urine whose pH ranges from 5.0 to 7.0. The pH value of urine can reach 4.5, which indicates an 800-fold excess of H+ in it compared to blood plasma. Acidification of urine in the proximal and distal renal tubules is a consequence of H+ secretion (acidogenesis). An important role in this process is played by carbonic anhydrase of the epithelium of the renal tubules. This enzyme accelerates the achievement of equilibrium between the slow reaction of hydration and dehydration of carbonic acid:
carbonic anhydrase
n2co3 - n2o + co2
As pH decreases, the rate of uncatalyzed H2CO3 > H2 + HCO3- increases. Thanks to acidogenesis, acidic components of the phosphate buffer (H + + HP04 2- > H2PO4-) and weak organic acids (lactic, citric, β-hydroxybutyric, etc.) are removed from the body. The release of H+ by the epithelium of the renal tubules occurs against an electrochemical gradient with energy costs, and at the same time reabsorption of an equivalent amount of Na+ occurs (a decrease in Na+ reabsorption is accompanied by a decrease in acidogenesis). Na+ reabsorbed due to acidogenesis forms sodium bicarbonate in the blood together with HCO3- secreted by the epithelium of the renal tubules
Na + + HC03 - > NaHC03
H+ ions secreted by the epithelium of the renal tubules interact with the anions of buffer compounds. Acidogenesis ensures the release of predominantly anions of carbonate and phosphate buffers and anions of weak organic acids.
Anions of strong organic and inorganic acids (CI-, S0 4 2-) are removed from the body by the kidneys due to ammoniogenesis, which ensures the excretion of acids and protects the urine pH from decreasing below the critical level of the distal tubules and collecting ducts. NH3, formed in the epithelium of the renal tubules during the deamination of glutamine (60%) and other amino acids (40%), entering the lumen of the tubules, combines with H+ formed during acidogenesis. Thus, ammonia binds hydrogen ions and removes the anions of strong acids in the form of ammonium salts.
Ammoniogenesis is closely related to acidogenesis, therefore the concentration of ammonium in the urine is directly dependent on the concentration of H+ in it: acidification of the blood, accompanied by a decrease in the pH of the tubular fluid, promotes the diffusion of ammonia from the cells. Ammonium excretion is also determined by the rate of its production and the rate of urine flow.
Chlorides play an important role in the regulation of acid excretion by the kidneys - an increase in HCO3- reabsorption is accompanied by an increase in chloride reabsorption. The chlorine ion passively follows the sodium cation. The change in chloride transport is a consequence of the primary change in the secretion of H+ ions and the reabsorption of HCO3 and is due to the need to maintain the electrical neutrality of tubular urine.
In addition to acidosis and ammoniogenesis, a significant role in the preservation of Na+ during blood acidification belongs to the secretion of potassium. Potassium, released from cells when the blood pH decreases, is intensively excreted by the epithelium of the renal tubules while simultaneously increasing the reabsorption of Na+ - this affects the regulatory effect of mineralocorticoids: aldosterone and deoxycorticosterone. Normally, the kidneys secrete predominantly acidic metabolic products, but with an increased intake of bases into the body, the urine reaction becomes more alkaline due to the increased secretion of bicarbonate and basic phosphate.
The gastrointestinal tract plays an important role in the excretory regulation of CBS. Hydrochloric acid is formed in the stomach: H+ is secreted by the gastric epithelium, and CI- comes from the blood. In exchange for chlorides, bicarbonate enters the blood during gastric secretion, but alkalization of the blood does not occur, since the CI- gastric juice is reabsorbed into the blood. In the intestine, the epithelium of the intestinal mucosa secretes alkaline juice rich in bicarbonates. In this case, H+ passes into the blood in the form of HCl. A short-term shift in the reaction is immediately balanced by the reabsorption of NaHC03 in the intestine. The intestinal tract, in contrast to the kidneys, which concentrate and release mainly K+ and monovalent cations from the body, concentrates and removes divalent alkaline ions from the body. With an acidic diet, the release of mainly Ca2+ and Mg2+ increases, and with an alkaline diet, the release of all cations increases.
Rental block
All buffer systems of the body are involved in maintaining acid-base homeostasis (the balance of optimal concentrations of acidic and basic components of physiological systems). Their actions are interconnected and are in a state of balance. The hydrocarbonate buffer is most associated with all buffer systems. Disturbances in any buffer system affect the concentrations of its components, so changes in the parameters of the hydrocarbonate buffer system can quite accurately characterize the body's CBS.
Blood CBS is normally characterized by the following metabolic parameters:
Plasma pH 7.4±0.05;
[HCO3-]=(24.4±3) mol/l - alkaline reserve;
рСО2=40 mm Hg - partial pressure of CO2 above the blood.
From the Henderson-Hasselbach equation for a bicarbonate buffer, it is obvious that when the concentration or partial pressure of CO2 changes, the blood CBS changes.
Maintaining the optimal value of the environmental reaction in various parts of the body is achieved through the coordinated work of buffer systems and excretory organs. A shift in the reaction of the medium to the acidic side is called acidosis, and basically – alkalosis. The critical values for preserving life are: a shift to the acidic side to 6.8, and to the basic side – 8.0. Acidosis and alkalosis can be respiratory or metabolic in origin.
Metabolic acidosis develops due to:
a) increased production of metabolic acids;
b) as a result of loss of bicarbonates.
Increased production of metabolic acids occurs with: 1) type I diabetes mellitus, prolonged, complete fasting or a sharp reduction in the proportion of carbohydrates in the diet;
2) lactic acidosis (shock, hypoxia, type II diabetes mellitus, heart failure, infections, alcohol poisoning).
Increased loss of bicarbonates is possible in the urine (renal acidosis), or with some digestive juices (pancreatic, intestinal).
Respiratory acidosis develops with hypoventilation elation of the lungs, which, regardless of the cause that caused it, leads to an increase in the partial pressure of CO2 to more than 40 mm Hg. Art. (hypercapnia). This happens with diseases of the respiratory system, hypoventilation of the lungs, depression of the respiratory center with certain drugs, for example, barbiturates.
Metabolic alkalosis observed with significant losses gastric juice due to repeated vomiting, as well as as a result of the loss of protons in the urine during hypokalemia, constipation (when alkaline products accumulate in the intestines; after all, the source of bicarbonate anions is the pancreas, the ducts of which open into the duodenum), as well as during prolonged taking alkaline foods and mineral water, the salts of which undergo hydrolysis by anion.
Respiratory (respiratory) alkalosis develops as a result of hypervelocity Ntilation of the lungs, leading to excessive removal of CO2 from the body and a decrease in its partial pressure in the blood to less than 40 mm. rt. Art. (hypocapnia). This happens when inhaling rarefied air, hyperventilation of the lungs, the development of thermal shortness of breath, excessive excitation of the respiratory center due to brain damage.
For acidosis as an emergency measure use intravenous infusion of 4–8% sodium bicarbonate, 3.66% solution of trisamine H2NC(CH2OH)3 or 11% sodium lactate. The latter, while neutralizing acids, does not emit CO2, which increases its effectiveness.
Alkaloses are more difficult to correct, especially metabolic ones (associated with disruption of the digestive and excretory systems). Sometimes a 5% solution of ascorbic acid is used, neutralized with sodium bicarbonate to pH 6 - 7.
Alkaline reserve- this is the amount of bicarbonate (NaHC03) (more precisely, the volume of CO2 that can be bound by blood plasma). This value can only conditionally be considered as an indicator of acid-base balance, since, despite the increased or decreased bicarbonate content, in the presence of appropriate changes in H2CO3, the pH can remain completely normal.
Since compensatory possibilities through breathing, initially used by the body, are limited, the decisive role in maintaining constancy passes to the kidneys. One of the main tasks of the kidneys is to remove H+ ions from the body in cases where, due to some reason, a shift towards acidosis occurs in the plasma. Acidosis cannot be corrected unless the appropriate amount of H ions is removed. The kidneys use 3 mechanisms:
1. Exchange of hydrogen ions into sodium ions, which, combining with the HCO3 anions formed in the tubular cells, are completely reabsorbed in the form of NaHCO,
The prerequisite for the release of H-ions using this mechanism is the carbonic anhydrase-activated reaction CO2 + H20 = H2CO3, and H2CO3 decomposes into H and HCO3 ions. In this exchange hydrogen ions to ions sodium, reabsorption of all sodium bicarbonate filtered in the glomeruli occurs.
2. Excretion of hydrogen ions in urine and the reabsorption of sodium ions also occurs by converting the alkaline salt of sodium phosphate (Na2HP04) into the acid salt of sodium diphosphate (NaHaPO4) in the distal tubules.
3. Formation of ammonium salts: ammonia, formed in the distal parts of the renal tubules from glutamine and other amino acids, promotes the release of H-ions and the reabsorption of sodium ions; NH4Cl is formed due to the combination of ammonia with HCl. The intensity of ammonia formation, necessary to neutralize strong HCl, is greater, the higher the acidity of the urine.
Table 3
Basic parameters of CBS
(average value in arterial blood)
40 mm. rt. Art.
(partial pressure of CO2 in blood plasma)
This component directly reflects the respiratory component in the regulation of CBS (CAR).
(hypercapnia) is observed with hypoventilation, which is characteristic of respiratory acidosis.
↓ (hypocapnia) is observed during hyperventilation, which is characteristic of respiratory alkalosis. However, changes in pCO2 may also be a consequence of compensation from metabolic disorders of the CBS. To distinguish these situations from each other, it is necessary to consider pH and [HCO3-]
95 mm. rt. Art. (partial pressure in blood plasma)
SB or SB
SB – standard plasma bicarbonate i.e. [НСО3-] ↓ - with metabolic acidosis, or with compensation of respiratory alkalosis.
For metabolic alkalosis or compensation for respiratory acidosis.
Additional indexes
BO or BB
(base buffers)
Buffer bases. This is the sum of all whole blood anions belonging to buffer systems.
BEFORE or BD
(base deficiency)
Base deficiency. This is the difference between the practical and proper BO value in metabolic acidosis. Defined as the number of bases that must be added to the blood to bring its pH to normal (at pCO2 = 40 mmHg tо = 38°C)
IO or BE
(base excess)
Base excess. This is the difference between the actual and expected BO values in metabolic alkalosis.
Normally, relatively speaking, there is neither a deficiency nor an excess of bases (neither DO nor IO). In fact, this is expressed in the fact that the difference between the expected and actual BO is under normal conditions within ±2.3 meq/l. The departure of this indicator from the normal range is typical for metabolic disorders of CBS. Abnormally high values are typical for metabolic alkalosis. Abnormally low – for metabolic acidosis.
Laboratory and practical work
Experience 1. Comparison of the buffer capacity of blood serum and phosphate BS
Measure ml
N flask
Blood serum (1:10 dilution)
Phosphate BS (diluted 1:10), pH = 7.4
Phenolphthalein (indicator)
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