Keywords
Endogenous acidsEndogenous basesBuffersProximal tubuleHenleʼs loopDistal tubeCollecting ductAs discussed in Chap. 1, the acid–base physiology deals with the maintenance of normal hydrogen ion concentration ([H+]) and pH in body fluids and is precisely regulated by an interplay between body buffers, lungs, and kidneys. In everyday life, the blood pH is under constant threat by endogenous acid and base loads. If not removed, these loads can cause severe disturbances in blood pH and thus impair cellular function. However, three important regulatory systems prevent changes in pH and thus maintain blood pH in the normal range. These protective systems, as stated, are buffers, lungs, and kidneys.
Production of Endogenous Acids and Bases
An acid is a proton donor, whereas a base is a proton acceptor. Under physiological conditions, the diet is a major contributor to endogenous acid and base production.
Endogenous Acids
This reaction is catalyzed by carbonic anhydrase (CA), an enzyme present in tissues and red blood cells but absent in plasma. When H2CO3 dissociates into CO2 and H2O (a process called dehydration), the CO2 is eliminated by the lungs. For this reason, H2CO3 is called a volatile acid . In addition to volatile acid, the body also generates nonvolatile (fixed) acids from cellular metabolism. These nonvolatile acids are produced from sulfur-containing amino acids (i.e., cysteine and methionine) and phosphoproteins. The acids produced are sulfuric acid and phosphoric acid, respectively. Other sources of endogenous nonvolatile acids include glucose, which yields lactic and pyruvic acids; triglycerides, which yield acetoacetic and β-hydroxybutyric acids (ketoacids); and nucleoproteins, which yield uric acid. Hydrochloric acid is also formed from the metabolism of cationic amino acids (i.e., lysine, arginine, and histidine). Sulfuric acid accounts for 50% of all acids produced. A typical North American diet produces 1 mmol/kg/day of endogenous nonvolatile acid. Under certain conditions, acids are produced from sources other than the diet. For example, starvation produces ketoacids, which can accumulate in the blood. Similarly, strenuous exercise generates lactic acid. Drugs such as corticosteroids cause endogenous acid production by enhancing catabolism of muscle proteins.
Endogenous Bases
Sources of acid and alkali production
Source | Acid produced | Alkali produced |
---|---|---|
Sulfur-containing amino acids (cysteine, cystine, methionine) | Sulfuric acid (H2SO4) | |
Phosphoproteins, phospholipids | Phosphoric acid (H2PO4) | |
Glucose | Lactic acid, pyruvic acid | |
Triglycerides | Acetoacetic acid, β-hydroxybutyric acid | |
Nucleoproteins | Uric acid | |
Organic cations | HCl | |
Diet with anionic amino acids (glutamate, aspartate) | HCO3 − | |
Citrate, lactate | HCO3 − |
Maintenance of Normal pH
Buffers
Phosphate buffers are effective in regulating intracellular pH more efficiently than extracellular pH. Their increased effectiveness intracellularly is due to their higher concentrations inside the cell. Also, the pKa of this system is 6.8, which is close to the intracellular pH.
Plasma proteins contain several ionizable groups in their amino acids that buffer either acids or bases. For example, the imidazole groups of histidine and the N-terminal amino groups have pKa that are close to extracellular pH and thus function as effective buffers. In blood, hemoglobin is an important protein buffer because of its abundance in red blood cells.
Extracellular buffering to an acid load is complete within 30 min. Subsequent buffering occurs intracellularly and takes several hours to complete. Most of this intracellular buffering occurs in bone. Bone becomes an important source of buffering acid load acutely by an uptake of H+ in exchange for Na+, K+, and bone minerals. These bone minerals rescue the HCO3 −/CO2 system in severe acidosis.
It is apparent from the Henderson–Hasselbalch Eq. 2.2 that any change either in [HCO3 −] or pCO2 can cause a change in blood pH. The acid–base disturbance that results from a change in plasma [HCO3 −] is termed a metabolic acid–base disorder whereas that due to a change in pCO2 is called a respiratory acid–base disorder.
Lungs
After buffers, the lungs are the second line of defense against pH disturbance. In a normal individual, pCO2 is maintained around 40 mmHg. This pCO2 is achieved by expelling the CO2 that is produced by cellular metabolism through the lungs. Any disturbance in the elimination of CO2 may cause a change in blood pH. Thus, alveolar ventilation maintains normal pCO2 to prevent an acute change in pH. Alveolar ventilation is controlled by chemoreceptors located centrally in the medulla and peripherally in the carotid body and aortic arch. Blood [H+] and pCO2 are important regulators of alveolar ventilation. The chemoreceptors sense the changes in [H+] or pCO2 and alter alveolar ventilatory rate. For example, an increase in [H+], i.e., a decrease in pH, stimulates ventilatory rate and decreases pCO2. These responses, in turn, raise pH (see Eq. 2.3). Conversely, a decrease in [H+] or an increase in pH depresses alveolar ventilation and causes retention of pCO2 so that the pH is returned to near normal. An increase in pCO2 stimulates ventilatory rate, whereas a decrease depresses the ventilatory rate. The respiratory response to changes in [H+] takes several hours to complete.
Kidneys
- 1.
Reabsorption of filtered HCO3 −
- 2.
Generation of new HCO3 − by titratable acid (TA) excretion
- 3.
Formation of HCO3 − from generation of NH4 +
Reabsorption of Filtered HCO3 −
Proximal tubule: 80%.
Loop of Henle: 10%.
Distal tubule: 6%.
Collecting duct: 4%.