**3. Respiratory and renal regulation of acid and base**

Excess acid is eliminated from the body by the lungs and the kidneys. In the lungs, acid is eliminated in the form of CO2, and in the kidneys, acid is excreted as acid phosphatase and ammonium. CO2 is lipid soluble, and it crosses the cell membranes in the lungs. Most of the CO2 produced in the tissue is eliminated by alveolar ventilation. Arterial and brain chemoreceptors can sense the acid and base excess, and respiratory system responds with hyper or hypo ventilation. As a result, pH is increased or decreased by increasing and decreasing pCO2 level. The regulation between CO2 and H2CO3 level is critically maintained when the blood travels through the lung capillaries. When strong acid is added, some HCO3 <sup>−</sup> become H2CO3 and blood PCO2 is increased. In acidosis, carbonic acid dissociate to CO2 and H2O. As a result, respiratory center is stimulated and it leads to hyperventilation. Hyperventilation eliminates these CO2 to maintain normal pH. In alkalosis, CO2 is retained by hypoventilation. This CO2 combines with H2O to produce H2CO3, and pH is maintained.

**187**

*Acidosis and Anion Gap*

retain HCO3

HCO3

and K+

duct. H+

and K+

NH4 +

Na+ , K+

*DOI: http://dx.doi.org/10.5772/intechopen.91760*

by the kidneys as NH4Cl, and (NH4)2SO4. The kidneys are largely responsible for K+

develops from increased K+

and NH4

by the collecting duct. Secreted H<sup>+</sup>

H2PO4, and is excreted in urine.

**4. Acidosis and buffer**

+

pH <7.38 and bicarbonate <22 mmol/L [12].

increased and it is compensated by renal H+

developed from metabolic disturbances.

and K+

The kidneys excrete acids, both respiratory and nonrespiratory origin and

kidneys also produce new bicarbonate to neutralize acids. Tubular cells contain

Bicarbonate is also produced from glutamine metabolism along with ammonium. Some NH4 diffuses to body fluid and converts to urea in the liver. The rest of the them excreted in urine. The tubules are impermeable to bicarbonate, and it cannot

In the apical membrane of the kidney tubules, sodium is reabsorbed in exchange for the hydrogen ion. Salts like sulfates, phosphates, ammonia combines the hydrogen ions and excrete it. The kidneys titrate less than half of the excreted acids and the rest is excreted as ammonium [11]. For every ammonium excreted in urine, one HCO3+<sup>−</sup> is reabsorbed. HCl and H2SO4 are produced during dietary protein metabolism reacts with NaHSO4, and produce NaCl and Na2SO4. These Na salts are excreted

absorption is increased in the collecting duct. In alkalosis, hypokalemia

exchange occur in the tubules. Serum potassium level also influences

are the principle urinary cations, and the principal urinary

is also buffered by urinary buffer HPO4

secretion and reduced K+

the renal acid-base balance. In hyperkalemia, potassium is available in an increased amount in the filtrate, and hydrogen will be scarce for exchange with HCO3 and there will be an imbalance. In hypokalemia, less potassium will be available for H+

exchange and hydrogen will be available to exchange with bicarbonate.

Acidosis results from a reduction in serum bicarbonate and cause secondary reduction of PaCO2 resulting in a low blood pH. It develops from the addition of hydrogen or removal of HCO3 from the body. PaCO2 in blood is 38 ± 2 mm of Hg and HCO3 is 24 ± 2 mmol/L. Metabolic acidosis is characterized by the blood

Acid and base disorders are: respiratory acidosis and respiratory alkalosis, and metabolic acidosis and metabolic alkalosis [13]. In respiratory acidosis, PaCO2 is

generation. In respiratory alkalosis, decreased PaCO2 is compensated by renal HCO3 excretion. In metabolic acidosis, HCO3 is reduced and it is compensated by hyperventilation and PaCO2 reduction. HCO3 is increased in metabolic alkalosis, and it is compensated by increasing PaCO2 by hypoventilation [14]. Usually, respiratory disorders cause derangements of CO2 level in the blood, and change in HCO3 level is

In the blood, Alkali is present mainly in the form of sodium bicarbonate, and bicarbonate is bound to other bases. Increase in BHCO3 and decrease in H2CO3

 is the urinary unmeasured ion. Chloride is an important anion in neutralizing positive ions, reabsorbed in the proximal convoluted tubule and secreted in urine

kidneys. The nephron reabsorbs all filtered bicarbonate in exchange for H+

be converted back to CO2 and H2O. So, the blood HCO3 level is increased.

<sup>−</sup> is predominantly regulated in the

is excreted in tubular lumen.

excretion and most of it is reabsorbed

absorption in the collecting

+

excretion, HCO3 retention and HCO3

<sup>−</sup> and H+

. The

. Newly formed

secretion is decreased

excretion, as

<sup>−</sup> to

<sup>−</sup> to stabilize the pH of blood. HCO3

carbonic anhydrase, that converts CO2 and H2O to HCO3

<sup>−</sup> is shunted to peritubular capillaries and H<sup>+</sup>

in the proximal tubule and in the loop of Henly. In acidosis, K+

anion is chloride. Urinary anion gap helps in estimating renal NH4

#### *Acidosis and Anion Gap DOI: http://dx.doi.org/10.5772/intechopen.91760*

*New Insights into Metabolic Syndrome*

**2. Normal acid-base balance**

body play a crucial role in removing excess H<sup>+</sup>

of acidosis.

corrected by the body buffer systems. Many clinical conditions develop acidosis, as well as ionic derangements and the only correction of the underlying cause can resolve it. There are equal numbers of cations and anions in the blood and among them there are some unmeasured anions. These unmeasured anions can contribute in the clinically important anion gap. In a healthy individual, there is an acceptable range of normal anion gap. But some conditions can increase or decrease this gap. Increased anion gap usually represents metabolic acidosis. Albumin and many other confounding factors influence the anion gap derangements. Accuracy in measuring anion gap is critically important for the evaluation

The body maintains its normal physiology by the strict balance of acid and base. The body maintains its normal arterial pH close to 7.4 at a range between 7.36–7.44, and the intracellular pH of the human body is 7.2 [11]. Normal acid-base balance is the balance between each hydrogen increase by the intake or production, and that is decreased by elimination. Acid-base balance is measured by measuring pH, CO2 and HCO3. In general, consuming animal protein add acid in the body, and consuming cereals and vegetables add alkali in the body. In oxidative metabolism, CO2 is produced in the tissue, and at a similar rate, that is eliminated by the lungs. So, pCO2 persists at about 5.33 kPa (40 mm of Hg). Different buffer systems of the

fat uses O2 and produce CO2 and H2O. Normal lungs efficiently remove most of the CO2. In oxidation of amino acids, carbon dioxide and water are produced along with the liberation of nitrogen as ammonia, a toxic material in the body. In the liver, the urea cycle utilizes the ammonia, where this toxic NH3 combines with CO2, and produce urea. In the proximal tubule and other renal epithelial cells, ammonia and bicarbonate are also produced from glutamine metabolism. Some of it returns to the body fluid through the renal veins and is metabolized in the liver. And the rest of the NH3 excreted in the lumen. So, NH3 does not exist in the body fluid. Most of the NH3 is excreted in the urine, and it plays an important role in removing H<sup>+</sup>

maintain normal acid-base balance. In the urine, NH3 binds hydrogen ion to pro-

Excess acid is eliminated from the body by the lungs and the kidneys. In the lungs, acid is eliminated in the form of CO2, and in the kidneys, acid is excreted as acid phosphatase and ammonium. CO2 is lipid soluble, and it crosses the cell membranes in the lungs. Most of the CO2 produced in the tissue is eliminated by alveolar ventilation. Arterial and brain chemoreceptors can sense the acid and base excess, and respiratory system responds with hyper or hypo ventilation. As a result, pH is increased or decreased by increasing and decreasing pCO2 level. The regulation between CO2 and H2CO3 level is critically maintained when the blood travels through the lung

is increased. In acidosis, carbonic acid dissociate to CO2 and H2O. As a result, respiratory center is stimulated and it leads to hyperventilation. Hyperventilation eliminates these CO2 to maintain normal pH. In alkalosis, CO2 is retained by hypoventilation.

This CO2 combines with H2O to produce H2CO3, and pH is maintained.

duce NH4, and it prevents excessive acidification of urine.

**3. Respiratory and renal regulation of acid and base**

capillaries. When strong acid is added, some HCO3

. Metabolism of carbohydrate and

<sup>−</sup> become H2CO3 and blood PCO2

to

**186**

The kidneys excrete acids, both respiratory and nonrespiratory origin and retain HCO3 <sup>−</sup> to stabilize the pH of blood. HCO3 <sup>−</sup> is predominantly regulated in the kidneys. The nephron reabsorbs all filtered bicarbonate in exchange for H<sup>+</sup> . The kidneys also produce new bicarbonate to neutralize acids. Tubular cells contain carbonic anhydrase, that converts CO2 and H2O to HCO3 <sup>−</sup> and H+ . Newly formed HCO3 <sup>−</sup> is shunted to peritubular capillaries and H<sup>+</sup> is excreted in tubular lumen. Bicarbonate is also produced from glutamine metabolism along with ammonium. Some NH4 diffuses to body fluid and converts to urea in the liver. The rest of the them excreted in urine. The tubules are impermeable to bicarbonate, and it cannot be converted back to CO2 and H2O. So, the blood HCO3 level is increased.

In the apical membrane of the kidney tubules, sodium is reabsorbed in exchange for the hydrogen ion. Salts like sulfates, phosphates, ammonia combines the hydrogen ions and excrete it. The kidneys titrate less than half of the excreted acids and the rest is excreted as ammonium [11]. For every ammonium excreted in urine, one HCO3+<sup>−</sup> is reabsorbed. HCl and H2SO4 are produced during dietary protein metabolism reacts with NaHSO4, and produce NaCl and Na2SO4. These Na salts are excreted by the kidneys as NH4Cl, and (NH4)2SO4.

The kidneys are largely responsible for K+ excretion and most of it is reabsorbed in the proximal tubule and in the loop of Henly. In acidosis, K+ secretion is decreased and K+ absorption is increased in the collecting duct. In alkalosis, hypokalemia develops from increased K+ secretion and reduced K+ absorption in the collecting duct. H+ and K+ exchange occur in the tubules. Serum potassium level also influences the renal acid-base balance. In hyperkalemia, potassium is available in an increased amount in the filtrate, and hydrogen will be scarce for exchange with HCO3 and there will be an imbalance. In hypokalemia, less potassium will be available for H+ and K+ exchange and hydrogen will be available to exchange with bicarbonate.

Na+ , K+ and NH4 + are the principle urinary cations, and the principal urinary anion is chloride. Urinary anion gap helps in estimating renal NH4 + excretion, as NH4 + is the urinary unmeasured ion. Chloride is an important anion in neutralizing positive ions, reabsorbed in the proximal convoluted tubule and secreted in urine by the collecting duct. Secreted H<sup>+</sup> is also buffered by urinary buffer HPO4 <sup>−</sup> to H2PO4, and is excreted in urine.
