Acid-base balance Introduction .
[1]. 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.
[2]. 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.
[3]. An acid is the proton donor (the substance that liberates hydrogen ion). A base is the proton acceptor (the substance that accepts hydrogen ion).
[4]. In spite of continuous production of acids in the body, the concentration of free hydrogen ion is kept almost constant at a pH of 7.4 with slight variations.
Hydrogen Ion and pH .
[1]. 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.
[2]. Because of this, the H+ shows severe effects on the physiological activities of the body even at low concentrations. The normal H+ concentration in the extracellular fluid (ECF) is 38 to 42 nM/L.
[3]. The pH is another term for H+ concentration that is generally used nowadays instead of ‘hydrogen ion concentration’ .An increase in H+ ion concentration decreases the pH (acidosis) and a reduction in H+ concentration increases the pH (alkalosis).
[4]. 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.
[5]. 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 .
[1]. It is difficult to determine the acid-base status in the ECF by direct methods. So, an indirect method is followed by using 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.
[2]. In addition to this, the pH of plasma is also determined by using an instrument called pH meter. Normal acid-base ratio is 1:20, i.e. the ratio of 1 part of CO2 (derived from H2 CO3 ) and 20 parts of HCO3 – .
[3]. 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:
1. Volatile acids .
2. Non-volatile acids.
1. Volatile Acids .
Volatile acids are derived from CO2 . 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 lungs.
2. Non-volatile Acids.
[1]. Non-volatile acids are produced during the metabolism of other nutritive substances such as proteins. These acids are real threat to the acid-base status of the body.
[2]. For example, sulfuric acid is produced during the metabolism of sulfur containing amino acids such as cysteine and metheonine; hydrochloric acid is produced during the metabolism of lysine, arginine and histidine.
[3]. Fortunately, body is provided with the best regulatory mechanisms to prevent the hazards of acid production.
Compensatory Mechanism .
[1]. Whenever there is a change in pH beyond the normal range, some compensatory changes occur in the body to bring the pH back to normal level.
[2]. The body has three different mechanisms to regulate acid-base status:
1. Acid-base buffer system, which binds free H+
2. Respiratory mechanism, which eliminates CO2
3. Renal mechanism, which excretes H+ and conserves the bases (HCO3 – ).
[4]. 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.
[5]. Whereas, the renal mechanism is slower and it takes few hours to 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 .
[1]. An acid-base buffer system is the combination of a weak acid (protonated substance) and a base – the salt (unprotonated substance).
[2]. Buffer system is the one, which acts immediately to prevent the changes in pH. Buffer system maintains pH by binding with free H+.
Types of Buffer Systems .
Body fluids have three types of buffer systems, which act under different conditions:
1. Bicarbonate buffer system .
2. Phosphate buffer system .
3. Protein buffer system.
1. Bicarbonate Buffer System .
Bicarbonate buffer system is present in ECF (plasma). It consists of the protonated substance, carbonic acid (H2 CO3 ) 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 (NaHCO3 ).
Mechanism of action of bicarbonate .
[1]. Buffer system Bicarbonate buffer system prevents the fall of pH in a fluid to which a strong acid like hydrochloric acid (HCl) is added. Normally, when HCl is mixed with a fluid, pH of that fluid decreases quickly because the strong HCl dissociates into H+ and Cl– .
[2]. But, if bicarbonate buffer system (NaHCO3 ) is added to the fluid with HCl, the pH is not altered much. This is because the H+ dissociated from HCl combines with HCO3 – of NaHCO3 and forms a weak H2 CO3 . This H2 CO3 in turn dissociates into CO2 and H2 O.
[3]. 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 .
[4]. It is prevented by adding H2 CO3 , which dissociates into H+ and HCO3 – . The hydroxyl group (OH) of NaOH combines with H+ and forms H2 O. And Na+ combines with HCO3 – and forms NaHCO3 .
[5]. 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+ is poor. So the rise in pH of the fluid is very mild.
Importance of bicarbonate buffer system .
[1]. Bicarbonate buffer system is not powerful like the other buffer systems because of the large difference between the pH of ECF (7.4) and the pKa of bicarbonate buffer system (6.1).
[2]. 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.
[3]. Concentration of HCO3 – is regulated by 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 .
[1]. This system consists of a weak acid, the dihydrogen phosphate (H2 PO4 – protonated substance) in the form of sodium dihydrogen phosphate (NaH2 PO4 ) and the base, hydrogen phosphate (HPO4 – unprotonated substance) in the form of disodium hydrogen phosphate (Na2 HPO4 ).
[2]. Phosphate buffer system is useful in the intracellular fluid (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 .
[1]. When a strong acid like hydrochloric acid is mixed with a fluid containing phosphate buffer, sodium dihydrogen phosphate (NaH2 PO4 – weak acid) is formed. This permits only a mild change in the pH of the fluid.
[2]. If a strong base such as sodium hydroxide (NaOH) is added to the fluid containing phosphate buffer, a weak base called disodium hydrogen phosphate (Na2 HPO4 ) is formed. This prevents the changes in pH.
Importance of phosphate buffer system .
[1]. Phosphate buffer system is more powerful than bicarbonate buffer system as it has a pKa of 6.8, which is close to the pH of the body fluids, i.e. 7.4. In addition to ICF, phosphate buffer is useful in tubular fluids of kidneys also.
[2]. It is because more phosphate ions are found in tubular fluid. In the red blood cells, the potassium ion concentration is higher than the sodium ion concentration.
[3]. So, the elements of phosphate buffer inside the red blood cells are in the form of potassium dihydrogen phosphate (KH2 PO4 ) and dipotassium hydrogen phosphate (K2 HPO4 ).
3. Protein Buffer System .
Protein buffer systems are present in the blood; both in the plasma and erythrocytes.
Protein buffer systems in plasma .
Elements of proteins, which form the weak acids in the plasma are:
i. C-terminal carboxyl group, N-terminal amino group and side-chain carboxyl group of glutamic acid .
ii. Side-chain amino group of lysine .
iii. Imidazole group of histidine.
Protein buffer systems in plasma are more powerful because of their high concentration in plasma and because of their pKa being very close to 7.4.
Protein buffer system in erythrocytes (Hemoglobin) .
[1]. 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.
[2]. The deoxygenated hemoglobin is a more powerful buffer than oxygenated hemoglobin because of the higher pKa.
[3]. When a hemoglobin molecule becomes deoxygenated in the capillaries, it easily binds with H+, which are released when CO2 enters the capillaries. Thus, hemoglobin prevents fall in pH when more and more CO2 enters the capillaries.
Regulation of Acid-base balance by Respiratory Mechanism .
[1]. 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.
[2]. Since carbonic acid is unstable, it splits into H+ and HCO3 – . Entire reaction is reversed in lungs when CO2 diffuses from blood into the alveoli of lungs .And CO2 is blown off by ventilation .
[3]. When metabolic activities increase, more amount of CO2 is produced in the tissues and the concentration of H+ increases as seen above.
[4]. Increased H+ concentration increases the 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 .
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| Regulation of acid-base balance |
Kidney maintains the acid-base balance of the body by the secretion of H+ and by the retention of HCO3 – .
Anion gap .
[1]. Anion gap is an important measure in the clinical evaluation of disturbances in acid-base status. Only few cations and anions are measured during routine clinical investigations.
[2]. Commonly measured cation is sodium and the unmeasured cations are potassium, calcium and magnesium. Usually measured anions are chloride and bicarbonate.
[3]. The unmeasured anions are phosphate, sulfate, proteins in anionic form such as albumin and other organic anions like lactate.
[4]. Difference between concentrations of unmeasured anions and unmeasured cations is called anion gap. Normal value of anion gap is 9 to 15 mEq/L.
[5]. It increases when concentration of unmeasured anion increases and decreases when concentration of unmeasured cations decreases.
[6]. Anion gap is a useful measure in the differential diagnosis (diagnosis of the different causes) of acid-base disorders particularly the metabolic acidosis.
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