Urinary Regulation of Acid Base Balance
The acid base balance is vital for normal bodily functions. When this equilibrium is disrupted, it can lead to severe symptoms such as arrhythmias and seizures. Therefore, this balance is tightly regulated. In this article, we will look at the buffering system, responses of the respiratory and urinary systems and relevant clinical conditions.
Information on the buffering system of the blood and responses of the respiratory system can be found here.
The urinary system utilises two methods to alter hydrogen ion level blood pH – excretion of hydrogen ions as dihydrogen phosphate or ammonia. In addition to this reabsorption and production of bicarbonate ions can be increased.
Excretion of Hydrogen Ions
The first is by moving hydrogen ions into the lumen, to react with phosphate ions to form dihydrogen phosphate (H2PO4–). This can then be excreted. The alpha intercalated cells are responsible for this. There is an increase in hydrogen-ATPase pumps on the luminal side of the alpha intercalated cells which actively transport hydrogen ions into the lumen. This can then bind to phosphate as only 85% of phosphate is reabsorbed, leaving a large portion for hydrogen ions to bind to it. The net result is an excretion of hydrogen ions and therefore an increase of pH.
The second method is to excrete hydrogen ions in the form of ammonium (NH4+). In the proximal convoluted tubule (PCT), glutamine is converted to glutamate and ammonium. Glutamate is converted to alpha-ketoglutarate which is then eventually turned to bicarbonate which can be reabsorbed in the blood. The ammonium can then dissociate to ammonium (NH3) and hydrogen ions, which is then reformed to ammonium on the luminal side to be excreted. Similarly, in the collecting duct, ammonia filtered from earlier segments of the kidney can bind to hydrogen ions secreted by the alpha intercalated cells to form ammonium which can be excreted.
Bicarbonate ions can also be reabsorbed in the kidneys which aid in the buffering system. Reabsorption takes place in the PCT. Hydrogen ions are secreted into the lumen via the Sodium-Hydrogen exchanger to combine with any filtered bicarbonate. This then forms carbonic acid (H2CO3), catalysed by carbonic anhydrase on the luminal side. Carbonic acid then dissociates into carbon dioxide and water, which both can diffuse into the cell. Here, the reaction is undone, and carbonic anhydrase inside the cell converts carbon dioxide and water to carbonic acid, which then dissociates into hydrogen ions and bicarbonate. Bicarbonate can then be transported into the blood whilst the hydrogen ions can be transported back into the lumen for the cycle to repeat.
The kidney is also able to produce bicarbonate. The metabolic activity of cells produces large amounts of carbon dioxide, which can then react with water to produce bicarbonate ions, which enter the plasma, and hydrogen ions to be transported into the lumen. This is useful as it also provides hydrogen ions to drive bicarbonate reabsorption. In addition to this bicarbonate can also be produced from amino acids, which produces NH4– ions which then enter the urine.
Clinical Relevance – Respiratory Acidosis
Respiratory acidosis is where there is an increase of carbon dioxide in the blood, the cause of which is due to a disorder in the respiratory system. Common causes include respiratory depression by opiates, disorders of the respiratory muscles such as in polio and airway obstructions such as in sleep apnoea. The buffering systems are overwhelmed and pH drops. Therefore, the kidneys have to excrete more hydrogen ions via the two methods previously discussed in addition to an increase in bicarbonate reabsorption.
Clinical Relevance – Respiratory Alkalosis
Respiratory alkalosis is associated with hyperventilation, which can occur due to hypoxaemia from high altitudes or a pulmonary embolus. The compensatory methods for respiratory alkalosis is the opposite of respiratory acidosis: due to the high levels of bicarbonate, hydrogen ions are reabsorbed to attempt to bring the pH down by decreasing hydrogen excretion and decreasing bicarbonate reabsorption and production.