Kidney plays an important role in maintenance of acid-base balance by excreting hydrogen ions and retaining bicarbonate ions.

Normally, urine is acidic in nature with a pH of 4.5 to 6. Metabolic activities in the body produce large quantity of acids (with lot of hydrogen ions), which threaten to push the body towards acidosis. However, kidneys prevent this.

Kidneys Prevent Acidosis by Two Ways

1. Reabsorption of bicarbonate ions (HCO₃⁻).
2. Secretion of hydrogen ions (H⁺).

About 4,320 mEq of bicarbonate ion is filtered by glomeruli every day. It is called the filtered load of bicarbonate.

Excretion of this much bicarbonate ions in urine will affect the acid-base balance of body fluids. So, bicarbonate ions must be taken back from renal tubule by reabsorption.

Reabsorption of Filtered Bicarbonate

Reabsorption of filtered bicarbonate ions occurs by secretion of hydrogen ions in renal tubules.

About 4,380 mEq of hydrogen ions appear every day in the renal tubule by means of filtration and secretion. Not all the hydrogen ions are excreted in urine. Out of 4,380 mEq, about 4,280 to 4,330 mEq of hydrogen ion is utilized for reabsorption of filtered bicarbonate. Only remaining 50 to 100 mEq is excreted. It results in the acidification of urine.

Secretion of hydrogen ions into renal tubules occurs by the formation of carbonic acid. Carbon dioxide formed in tubular cells or derived from tubular fluid combines with water to form carbonic acid in the presence of carbonic anhydrase.

This enzyme is available in large quantities in epithelial cells of the renal tubules. Carbonic acid immediately dissociates into hydrogen ions and bicarbonate ions.

Hydrogen ion is secreted into lumen of proximal convoluted tubule, distal convoluted tubule and collecting duct. Distal convoluted tubule and collecting duct have a special type of cells called intercalated cells (I cells).

Two Pumps Involved in Hydrogen Ion Secretion

Mechanisms Involved in Secretion of Hydrogen Ions

Kidney plays an important role in preventing metabolic acidosis by excreting hydrogen ions.

Excretion of hydrogen ions occurs by three mechanisms:

1. Bicarbonate mechanism.
2. Phosphate mechanism.
3. Ammonia mechanism.

Bicarbonate Mechanism

All the bicarbonate filtered into renal tubules is reabsorbed. About 80% of it is reabsorbed in proximal convoluted tubule; 15% in Henle’s loop and 5% in distal convoluted tubule and collecting duct.

Reabsorption of bicarbonate utilizes the hydrogen secreted into renal tubules.

Hydrogen secreted into renal tubule combines with filtered bicarbonate forming carbonic acid. Carbonic acid dissociates into carbon dioxide and water in the presence of carbonic anhydrase. Carbon dioxide and water enter the tubular cell.

In tubular cells, carbon dioxide combines with water to form carbonic acid. It immediately dissociates into hydrogen and bicarbonate. Bicarbonate from tubular cell enters the interstitium. Simultaneously sodium is reabsorbed from renal tubule under the influence of aldosterone. Sodium enters the interstitium and combines with bicarbonate to form sodium bicarbonate. Now hydrogen secreted into tubular lumen from the cell in exchange for sodium.

Thus, for every hydrogen ion secreted into lumen of tubule, one bicarbonate ion is reabsorbed from the tubule. In this way, kidneys conserve the bicarbonate.

Reabsorption of filtered bicarbonate is an important factor in maintaining pH of the body fluids.

Phosphate Mechanism

In the tubular cells, carbon dioxide combines with water to form carbonic acid. It immediately dissociates into hydrogen and bicarbonate. Bicarbonate from tubular cell enters the interstitium.

Simultaneously, sodium is reabsorbed from renal tubule under the influence of aldosterone. Sodium enters the interstitium and combines with bicarbonate. Hydrogen ion is secreted into tubular lumen from the cell in exchange for sodium.

Hydrogen ion, which is secreted into renal tubules, reacts with phosphate buffer system. It combines with sodium-hydrogen phosphate to form sodium-dihydrogen phosphate.

Sodium-dihydrogen phosphate is excreted in urine. Hydrogen ion, which is added to urine, makes it acidic. It happens mainly in distal tubule and collecting duct because of the presence of large quantity of sodium-phosphate in these segments.

Ammonia Mechanism

This is the most important mechanism by which kidneys excrete hydrogen ions and make urine acidic.

In tubular epithelial cells, ammonia is formed when amino acid glutamine is converted into glutamic acid in the presence of enzyme glutaminase. Ammonia is also formed by deamination of some amino acids such as glycine and alanine.

Ammonia (NH₃) formed in tubular cells is secreted into tubular lumen in exchange for sodium ion. It combines with hydrogen ion to form ammonium (NH₄).

Tubular cell membrane is not permeable to ammonium. Therefore, it remains in the lumen and combines with sodium acetoacetate to form ammonium acetoacetate and is excreted through urine.

Thus, hydrogen ion is added to urine in the form of ammonium compounds and helps in acidification of urine.

This process takes place mostly in proximal convoluted tubule because the cells of this segment are rich in glutaminase.

Acidosis

Acidosis is a condition characterized by abnormal increase in acidity of blood and body fluids with reduction in pH below the normal range.

Acidosis is produced by:

1. Increase in partial pressure of carbon dioxide in the body fluids particularly in arterial blood.
2. Decrease in bicarbonate concentration.

Alkalosis

Alkalosis is a condition characterized by abnormal increase in alkalinity of blood and body fluids with increase in pH above the normal range.

Alkalosis is produced by:

1. Decrease in partial pressure of carbon dioxide in arterial blood.
2. Increase in bicarbonate concentration.

Since partial pressure of carbon dioxide in arterial blood is controlled by lungs, acid-base disturbances produced by the change in arterial carbon dioxide are called respiratory disturbances.

On the other hand, disturbances in acid-base status produced by the change in bicarbonate concentration are called metabolic disturbances.

Four Types of Acid-Base Disturbances

1. Respiratory acidosis.
2. Respiratory alkalosis.
3. Metabolic acidosis.
4. Metabolic alkalosis.

1. Respiratory Acidosis

Respiratory acidosis is the acidosis caused by alveolar hypoventilation.

During hypoventilation, lungs fail to expel carbon dioxide, which accumulates in the tissues.

Carbon dioxide is the major end product of oxidation of carbohydrates, proteins and fats.

Carbon dioxide accumulates in blood where it reacts with water to form carbonic acid, which is called respiratory acid. Carbonic acid dissociates into hydrogen and bicarbonate. Increased hydrogen concentration in blood leads to decrease in pH and acidosis.

2. Respiratory Alkalosis

Respiratory alkalosis is the alkalosis caused by alveolar hyperventilation.

Hyperventilation causes excess loss of carbon dioxide from the body.

Loss of carbon dioxide leads to decreased formation of carbonic acid and decreased release of hydrogen ions. Decreased hydrogen ion concentration increases the pH leading to respiratory alkalosis.

3. Metabolic Acidosis

Metabolic acidosis is the acid-base imbalance characterized by excess accumulation of organic acids in the body, which is caused by abnormal metabolic processes.

Organic acids such as lactic acid, ketoacids and uric acid are formed by normal metabolism.

The quantity of these acids increases due to abnormality in metabolism.

4. Metabolic Alkalosis

Metabolic alkalosis is the acid-base imbalance caused by loss of excess hydrogen ions resulting in increased bicarbonate concentration.

Some of the endocrine disorders, renal tubular disorders, etc., cause metabolic disorders leading to loss of hydrogen ions. It increases bicarbonate ions and pH in the body leading to metabolic alkalosis.

Biochemical Changes in Arterial Blood During Acid-Base Disturbance