Urine Acidification

Intercalated cells in the walls of collecting ducts are capable of the active transport of hydrogen ions into the tubular lumen to acidify the urine. This system can generate a difference between blood and urine of about 3 pH units, so if blood pH is 7.4, urine with a pH of 4.4 can be formed.

The secretion of hydrogen ions by interca­lated cells is regulated in part by the concentra­tions of carbon dioxide and bicarbonate ions in the plasma and other extracellular fluids. if carbon dioxide concentration increases or if bicarbonate ion concentration decreases, the rate of hydrogen ion secretion accelerates, and urine becomes more acidic. The importance and relevance of this regulation by carbon

Figure 23-13. Formation and secretion of hydrogen and bicarbonate ions by intercalated cells. Formation of hydrogen and bicarbonate from water and carbon dioxide in the cell is promoted by the action of intracel­lular carbonic anhydrase.

dioxide or bicarbonate to the regulation of overall acid-base balance is discussed in a later section of this chapter.

some of the secreted hydrogen ions combine with HPO₄^-2 ions in the tubular fluid to form H₂PO₄^-. In this manner, HPO₄^-2 acts as an intratubular buffer to reduce the concentration of free hydrogen ions and prevent the urine pH from dropping too low. The phosphate ions originally entered the tubular fluid as part of the glomerular filtrate.

Regulation of Acid-Base Balance

The pH of blood plasma and other extracellular fluids is maintained relatively constant within a narrow range (about 7.35 to 7.45). It is important to maintain this constancy because enzyme activity and metabolic processes require close control of pH for optimal function. Three major mechanisms function together to prevent the development of an abnormal pH. These are (1) extracellular and intracellular chemical buffers, (2) ventilatory control of plasma carbon dioxide, and (3) urinary excretion of bicarbon­ate or an acid urine as needed.

Extracellular and Intracellular Buffers

A chemical buffer system acts to maintain a constant pH by either donating or removing free hydrogen ions in a solution (see Chapter 2).

The bicarbonate buffer system is quantita­tively the most important chemical buffer in blood plasma and other extracellular fluids. Bicarbonate is the base in this system, and the acid is carbonic acid. However, because car­bonic acid is difficult to measure and in body fluids it is in equilibrium with carbon dioxide, the levels of carbon dioxide are routinely used as indicators of carbonic acid levels.

The bicarbonate buffer system is the most important body buffer system from a physio­logic standpoint, because the concentrations of the components of the system can be rapidly adjusted by changes in either renal excretion of bicarbonate or pulmonary ventilation to remove carbon dioxide. Bicarbonate is avidly reab­sorbed by renal tubules, but a renal threshold value permits rapid excretion of excess bicar­bonate. Also, plasma carbon dioxide levels are normally the primary regulator of ventilation, so these levels are also under constant control.

Figure 23-14 summarizes the roles of the urinary and respiratory systems in maintaining the concentrations of the components of the bicarbonate buffer system.

Both intracellular and extracellular proteins function as buffers; that is, these proteins are capable of accepting excess hydrogen ions or donating free hydrogen ions to assist in the maintenance of a stable pH. Because of the large quantity of intracellular proteins in organs such as skeletal muscle, intracellular proteins account for a large percentage of the total buff­ering capacity in the body. However, intracel­lular buffers cannot be as easily regulated as the bicarbonate buffer system in the extracellular fluid, and hydrogen ions from the extracellular fluid must enter cells to be buffered by the intracellular proteins (Fig. 23-14). Hemoglobin proteins in erythrocytes are a major contributor to the total buffering capacity of whole blood.

Acids and bases are produced by normal cellular metabolism and are constantly being added to the ECF (Figure 23-14). Acids and bases are also added to the ECF by gastrointes­tinal absorption. Normally, these additions are balanced by the actions of the urinary and respiratory systems so that extracellular fluid pH (Fig. 23-14) and the status of body buffer systems, including intracellular proteins, remain stable. However, the ability of these mecha­nisms to maintain a normal pH can be over­whelmed during metabolic disturbances or after the absorption of large amounts of acids or bases from the gastrointestinal tract.

Ruminal or lactic acidosis is seen in rumi­nants that ingest large amounts of carbohy­drates, usually grain, over a short period.

Figure 23-14. Primary factors affecting extracellular fluid pH. The A^- refers to a variety of anions such as lactate. The arrow between intracellular and the extracellular fluids indicates that exchanges can occur in either direction, but this exchange is limited by the abilities of the different ions to cross cell membranes.

The sudden ingestion of the concentrated carbohydrates alters the microbial popula­tion in the rumen, favoring the rapid growth of organisms that produce lactic acid. The rapid increase in lactic acid absorption into the blood overwhelms the ability of the pH regulatory systems, and systemic acidosis develops.

Classification of Alkalosis and Acidosis and Compensation

Alkalosis is a condition in which the pH of body fluids (including blood) is abnormally high, and acidosis is a condition in which the pH is abnormally low. Acidosis or alkalosis can be classified as being either metabolic or respi­ratory, to indicate the cause of the pH imbal­ance. The term respiratory refers to acid-base imbalances that come about as a result of primary or initial changes in carbon dioxide levels. The term metabolic refers to all other causes of acid-base imbalances.

When an acid-base imbalance arises and the buffering capacities of the extracellular and intracellular chemical buffers are overwhelmed, the body systems primarily responsible for acid-base balance (respiratory and urinary) should respond. This response may lead to a state of compensation, so that the acid-base imbalance is less severe than if the compensa­tion (or response) had not occurred. For example, chronic lung diseases may result in an accumulation of carbon dioxide and a respiratory acidosis. The kidneys compen­sate for the respiratory acidosis by produc­ing a more acidic urine and retaining base (bicarbonate).

Because of its importance as the major extra­cellular buffer system and because the compo­nents of the system can be readily determined in clinical laboratories, the status of the bicar­bonate buffer system is used to evaluate overall acid-base balance. The primary cause of acido­sis or alkalosis is routinely diagnosed by evalu­ation of the bicarbonate buffer system.

Metabolic alkalosis is a primary increase in bicarbonate ions. Causes include excessive ingestion of alkaline salts or gastric vomiting, during which hydrochloric acid is lost from the body fluids. The body compensates for meta­bolic alkalosis by hypoventilation to retain carbon dioxide and by increasing urinary bicar­bonate excretion.

Metabolic acidosis is a primary decrease in bicarbonate ions. Causes include (1) excessive loss of bicarbonate via diarrhea (e.g., calf scours); (2) excessive formation of metabolic acids as a result of metabolic disturbances (e.g., diabetes mellitus, starvation, and lactic acidosis during shock); (3) inability of the kidneys to excrete acid (e.g., renal failure); and (4) absorption of excess acid from the gastro­intestinal tract (e.g., ruminal acidosis). The body compensates for metabolic acidosis by hyperventilation and excretion of a more acid urine if possible.

Respiratory alkalosis is a primary deficit in carbon dioxide (hypocapnia is low blood carbon dioxide). Causes include (1) exposure to high altitudes, where low oxygen tension causes hyperventilation; (2) a high fever, which may produce hyperventilation; and (3) inflam­mation or diseases of the brain, which stimulate the respiratory centers. The kidneys compen­sate for respiratory alkalosis by increasing excretion of bicarbonate ions in the urine.

Respiratory acidosis is a primary excess of carbon dioxide (hypercapnia is elevated blood carbon dioxide). Causes include pneumonia, pulmonary fibrosis, pulmonary edema, airway obstructions, and breathing air that is high in carbon dioxide. The kidneys compensate for the primary respiratory problem by excreting a more acid urine and secreting additional bicar­bonate into the blood. Note in Figure 23-13 that a bicarbonate ion is also produced when intercalated cells generate a hydrogen ion for urine acidification, and that the bicarbonate ion can be secreted into the blood. Plasma levels of bicarbonate may increase as the compensatory response continues.