Acid-Base Balance Introduction
- Acid-base balance is very important for the homeostasis of the body and almost all the physiological activities depend upon the acid-base status of the body. Acids are constantly produced in the body. However, the acid production is balanced by the production of bases so that the acid-base status of the body is maintained.
- An acid is the proton donor (the substance that liberates hydrogen ions). A base is the proton acceptor (the substance that accepts hydrogen ions).
- In spite of the continuous production of acids in the body. the concentration of free hydrogen ions is kept almost constant at a pH of 7.4 with slight variations.
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Hydrogen Ion And PH
- Hydrogen ion (H+) contains only a single proton (positively charged particle), which is not orbited by any electron. Therefore, it is the smallest ionic particle. However, it is highly reactive. Because of this, the H+ shows severe effects on the physiological activities of the body even at low concentrations.
- The normal H+ concentration in ECF is 38-42 nM/L. The pH is another term for H+ concentration that is generally used nowadays instead of ‘hydrogen ion concentration’. The pH scale was introduced in order to simplify the mathematical handling of large numbers.
- The negative logarithm of H+ concentration is taken for calculating the pH as given below.
- An increase in H+ ion concentration decreases the pH (acidosis) and a reduction in H+ concentration increases the pH (alkalosis).
- An increase in pH by one-fold requires a tenfold decrease in H+ concentration.
- In a healthy person, the pH of the ECF is 7.40 and it varies between 7.38 and 7.42. The maintenance of acid-base status is very important for homeostasis because even a slight change in pH below 7.38 or above 7.42 will cause serious threats to many physiological functions.
Determination Of Acid-Base Status
It is difficult to determine the acid-base status in the ECF by direct methods. So, an indirect method is followed by using the Henderson-Hasselbalch equation. In this, to determine the pH of a fluid, the concentration of bicarbonate ions (HCO3–) and the CO2 dissolved in the fluid are measured. The pH is calculated as follows:
- In addition to this, the pH of plasma is also determined by using an instrument called a pH meter. The normal acid-base ratio is 1:20, i.e. the ratio of 1 part of CO2 (derived from H2CO3) and 20 parts of HCO3–. If this ratio is altered, the pH also is altered leading to either acidosis or alkalosis.
- Thus, the pH of arterial blood is an indirect measurement of H+ concentration and it reflects the balance of CO2, and HCO3–.
Regulation Of Acid-Base Balance
Body is under constant threat of acidosis because of the production of large amount of acids.
Generally, two types of acids are produced in the body:
- Volatile acids
- Nonvolatile acids.
1. Volatile Acids: Volatile acids are derived from CO2. A large quantity of CO2 is produced during the metabolism of carbohydrates and lipids. This CO2 is not a threat because it is almost totally removed through expired air by the lungs.
2. Nonvolatile Acids:
- Nonvolatile acids are produced during the metabolism of other nutritive substances such as proteins. These acids are a real threat to the acid-base status of the body.
- For example, sulfuric acid is produced during the metabolism of sulfur-containing amino acids such as cysteine and methionine; and hydrochloric acid is produced during the metabolism of lysine, arginine, and histidine. Fortunately, the body is provided with the best regulatory mechanisms to prevent the hazards of acid production.
Compensatory Mechanism:
Whenever there is a change in pH beyond the normal range, some compensatory changes occur in the body to bring the pH back to a normal level. The body has three different mechanisms to regulate acid-base status:
- Acid-base buffer system, which binds free H+ ions
- A respiratory mechanism, which eliminates CO2
- Renal mechanism, which excretes H+ and conserves the bases (HCO3–)
Among the three mechanisms, the acid-base buffer system is the fastest one and it readjusts the pH within seconds. The respiratory mechanism does it in minutes. Whereas, the renal mechanism is slower and it takes a few hours to a few days to bring the pH back to normal. However, the renal mechanism is the most powerful mechanism than the other two in maintaining the Acid-base balance of the body fluids.
Regulation Of Acid-Base Balance By Acid-Base Buffer System Definition
The buffer system maintains pH by binding with free H+ ions. An acid-base buffer system is the combination of a weak acid (protonated compound) and a base – the salt (unprotonated compound). The buffer system is the one, which acts immediately to prevent the changes in pH.
Types of Buffer Systems: The body fluids have three types of buffer systems, which act under different conditions:
- Bicarbonate buffer system
- Phosphate buffer system
- Protein buffer system.
1. Bicarbonate Buffer System:
This buffer system is present in ECF (plasma). It consists of the protonated substance-carbonic acid (H2CO3– ) which is a weak acid and the unprotonated substance- HCO3– which is a weak base, HCO3– is in the form of salt, i.e. sodium bicarbonate (NaHCQ3).
Mechanism of action of bicarbonate buffer system:
- A bicarbonate buffer system prevents the fall of pH in a fluid to which a strong acid like hydrochloric acid (HCI) is added:
- Normally, when HCI is mixed with a fluid, the pH of the fluid decreases quickly because the strong HCI dissociates into H and CI.
- But, if a bicarbonate buffer system (NaHCO3) is added to the fluid with HCI; the pH is not altered much. This is because the H+ dissociated from HCI combines with HCO3– of NaHCO, and forms a weak H2CO3. This H2CO3 in turn dissociates into CO2 and H2O.
- The bicarbonate buffer system also prevents the increase in pH in a fluid to which a strong base like sodium hydroxide (NaOH) is added.
- Normally, when a base (NaOH) is added to a fluid, pH increases. It is prevented by adding HCO3– which dissociates into H+ and HCO3–. The hydroxyl group (OH) of NaOH combines with H+ and forms H2O. And Na+ combines with HCO3–, and forms NaHCO3. NaHCO3 is a weak base and it prevents the increase in pH by the strong NaOH.
- As sodium bicarbonate is a very weak base, its association with H+ ions is poor. So the rise in pH of the fluid is very mild.
Importance of bicarbonate buffer system:
- The bicarbonate buffer system is not powerful like the other butter systems because of the large difference between the pH of ECF (7.4) and the pK of the bicarbonate buffer system. But this buffer system plays an important role in maintaining the pH of body fluids than the other buffer systems.
- It is because the concentration of two components (HCO3– and CO2) of this buffer system is regulated separately by two different mechanisms. The concentration of HCO3– , is regulated by the kidney, and the concentration of CO2 is regulated by the respiratory system. These two regulatory mechanisms operate constantly and simultaneously, making this system more effective.
2. Phosphate Buffer System:
- This system consists of a weak acid, the dihydrogen phosphate (H2PO2 – protonated substance) in the form of sodium dihydrogen phosphate (NaH2PO4) and the base; hydrogen phosphate (HPO4, – unprotonated sub- stance) in the form of disodium hydrogen phosphate (Na2HPO4).
- A phosphate buffer system is useful in the ICF (in red blood cells or other cells) as the concentration of phosphate is more in ICF than in ECF.
Mechanism of phosphate buffer system: When a strong acid like hydrochloric acid is mixed with a fluid containing phosphate buffer, sodium dihydrogen phosphate (NaH2PO4 -weak acid) is formed. This permits only a mild change in the pH of the fluid.
If à strong base such as sodium hydroxide (NaOH) is added to the fluid containing phosphate buffer, a weak base called disodium hydrogen phosphate (Na2HPO4) is formed. This prevents the changes in pH.
Importance of phosphate buffer system:
- bicarbonate buffer system as it has a pk of 6.8 which is a Phosphate buffer system is more powerful than close to the pH of the body fluids, 7.4. In addition to ICF, phosphate buffer is useful in the tubular fluids of kidneys also. It is because more phosphate ions are found in the tubular fluid.
- is higher than the sodium ion concentration. So, the In the red blood cells, the potassium ion concentration elements of phosphate buffer inside the red blood cells are in the form of potassium dihydrogen phosphate (KH2PO4) and dipotassium hydrogen phosphate (K2HPO4).
3. Protein Buffer System: The protein buffer systems are present in the blood; both in the plasma and erythrocytes.
Protein buffer systems in plasma: The elements of proteins, which form the weak acids in the plasma are:
- C-terminal carboxyl group, N-terminal amino group, and side chain carboxyl group of glutamic acid
- Side chain amino group of lysine
- Imidazole group of histidine.
The protein buffer systems in plasma are more powerful because of their high concentration in plasma and because of their pK being very close to 7.4.
Protein buffer in erythrocytes (Hemoglobin):
- Hemoglobin is the most effective protein buffer and the major buffer in blood. Due to its high concentration than the plasma proteins, hemoglobin has about six times more buffering capacity than the plasma proteins. The deoxygenated hemoglobin is a more powerful buffer than oxygenated hemoglobin because of the higher pK.
- When a hemoglobin molecule becomes deoxygenated in the capillaries, it easily binds with H+ ions, which are released when CO2 enters the capillaries. Thus, hemoglobin prevents a fall in pH when more and more CO2 enters the capillaries.
Regulation Of Acid-Base Balance By Respiratory Mechanism:
The lungs play an important role in the maintenance of acid-base balance by removing CO2 which is produced during various metabolic activities in the body. This CO2 combines with water to form carbonic acid.
Since carbonic acid is unstable, it splits into H+ ion and HCO3–
.CO2 + H2O → H2CO3 → H++ HCO3–
The entire reaction is reversed in the lungs when CO2 diffuses from the blood into the alveoli of the lungs.
H++HCO → H2CO3 → CO2 + H2O
And CO2 is blown off by ventilation. When metabolic activities increase, more amount of CO2 is produced in the tissues and the concentration of H+ ion increases as seen above. The increased H+ ion concentration increases pulmonary ventilation (hyperventilation) by acting through the chemoreceptors. Due to hyperventilation, the excess of CO2 is removed from the body.
Regulation Of Acid-Base Balance By Renal Mechanism:
The kidney maintains the acid-base balance of the body by the secretion of H+ ions and by the retention of HCO3.
Applied Physiology Disturbances Of Acid-Base Status
Acidosis:
Acidosis is the reduction in pH (increase in H+ ion concentration) below the normal range. The acidosis is produced by:
- Increase in partial pressure of CO2 in the body fluids particularly in arterial blood or
- Decrease in HCO3– concentration.
Alkalosis: Alkalosis is the increase in pH (decrease in H+ ion concentration) above the normal range.
The alkalosis is produced by:
- Decrease in partial pressure of CO2 in the arterial blood or
- Increase in HCO3– concentration.
Since the partial pressure of CO2 (pCO2) in arterial blood is controlled by the lungs, the acid-base disturbances produced by the change in arterial pCO2 are called respiratory disturbances. On the other hand, the disturbances in acid-base status produced by the change in HCO3– concentration are generally called metabolic disturbances.
Thus the acid-base disturbances are:
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis.
1. Respiratory Acidosis:
- Respiratory acidosis is acidosis that is caused by alveolar hypoventilation. During hypoventilation, the lungs fail to expel CO2 which is produced in the tissues. CO2 is the major end product of the oxidation of carbohydrates, proteins, and fats.
- CO2 accumulates of in the blood where it reacts with water to form carbonic acid which is called respiratory acid. Carbonic acid dissociates into H+ and HCO3– .The increased H+ concentration in the blood leads to a decrease in pH and acidosis.
- The normal partial pressure of CO2 in arterial blood is about 40 mm Hg. When it increases above 60 mm Hg acidosis occurs.
Causes of Excess CO2, in the Body: Hypoventilation (decreased ventilation) is the primary cause for excess CO2 in the body. Some of the conditions when an increase in pCO2, and respiratory acidosis occur due to hypoventilation are listed in.
2. Respiratory Alkalosis:
- Respiratory alkalosis is the alkalosis that is caused by alveolar hyperventilation. Hyperventilation causes excess loss of CO2 from the body. Loss of CO2 leads to decreased formation of carbonic acid and decreased release of H+. Decreased H+ concentration increases the pH leading to respiratory alkalosis.
- When the partial pressure of CO2 in arterial decreases glycolysis in some abnormal conditions like circulatory below 20 mm Hg, alkalosis occurs.
Causes of Decrease in CO2, in the Body: Hyperventilation is the primary cause for loss of excess CO2 from the body because during hyperventilation lot of CO2 is expired through the respiratory tract leading to decreased pCO2. Some of the conditions when decreased pCO2 and respiratory alkalosis occur due to hyperventilation are given in.
3. Metabolic Acidosis:
Metabolic acidosis is the acid-base imbalance characterized by the excess accumulation of organic acids in the body which is caused by abnormal metabolic processes. Organic acids such as lactic acid, ketoacidosis, and uric acid are formed by normal metabolism. The quantity of these acids increases due to abnormality in the metabolism.
Causes of Metabolic Acidosis:
- Lactic acid: The amount of lactic acid increases during anaerobic glycolysis in some abnormal conditions like circulatory shock.
- Ketoacids: The amount of ketoacidosis increases because of insulin deficiency as in the case of diabetes mellitus. In diabetes mellitus, glucose is not utilized due to a lack of insulin. So, lipids are utilized for the liberation of energy resulting in the production of excess acetoacetic acid and beta-hydroxybutyric acid.
- Uric acid:
- The amount of uric acid increases in the body due to the failure of excretion. Normally uric acid is excreted by the kidneys. But in renal diseases, the kidneys fail to excrete the uric acid.
- Some of the conditions when the metabolic acids increase in the body resulting in metabolic acidosis are listed in.
4. Metabolic Alkalosis:
- Metabolic alkalosis is the acid-base imbalance caused by the loss of excess H+ resulting in increased HCO3– concentration. Some of the endocrine disorders, renal tubular disorders, etc. cause metabolic disorders leading to loss of H+. It increases HCO3– ,” and pH in the body leading to metabolic alkalosis.
- Some of the conditions when excess H+ is lost and HCO3– content increases leading to metabolic alkalosis are given in.
Clinical Evaluation Of Disturbances In Acid-Base Status Anion Gap
- The anion gap is an important measure in the clinical evaluation of disturbances in acid-base status. Only a few cations and anions are measured during routine clinical investigations. Commonly measured cation is sodium and the unmeasured cations are potassium, calcium, and magnesium.
- Usually measured anions are chloride and bicarbonate. The unmeasured anions are phosphate, sulfate, proteins in an anionic form such as albumin, and other organic anions like lactate.
The difference between the concentrations of unmeasured anions and unmeasured cations is called the anion gap. It is calculated as:
Anion gap = [Na] – [HCO] – [CI]
=144 – 24 – 108 mEq/L
= 12 mEq/L
- The normal value of the anion gap is 9-15 mEq/L. It increases when the concentration of unmeasured anion increases and decreases when the concentration of unmeasured cations decreases.
- The anion gap is a useful measure in the differential diagnosis (diagnosis of the different causes) of acid-base disorders, particularly metabolic acidosis. The variations of the anion gap.
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