**4. Acidosis and buffer**

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

Acid and base disorders are: respiratory acidosis and respiratory alkalosis, and metabolic acidosis and metabolic alkalosis [13]. In respiratory acidosis, PaCO2 is increased and it is compensated by renal H+ excretion, HCO3 retention and HCO3 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 developed from metabolic disturbances.

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

results in alkalosis, and decrease in BHCO3 and increase in H2CO3 results in acidosis [13]. The body contains many acids. They are hydrochloric acid, carbonic acid, citric acid, lactic acid, phosphoric acid and carboxylic acid. Acute metabolic acidosis is developed by the overproduction of organic acids, like lactic acid and keto acid. Chronic acidosis is caused by bicarbonate wasting and impaired urinary acidification.

Blood cells are more acidic than serum, which influences the distribution of electrolyte and water between them. These transports took place with the oxygenation and reduction of hemoglobin and shift of bases (Na<sup>+</sup> , K+ ) due to changes in pH. Under normal environment Na+ and K+ do not diffuse through the cell wall. Shifting of water and electrolyte through membrane results from the change in anion (HCO3 <sup>−</sup> and Cl<sup>−</sup>) and H+ concentration, and that changes in cell volume. CO2, relative electrolyte concentration and weak acid concentrations are three independent variables that regulate blood pH [15].

The body has different buffer systems to maintain the normal pH of the body. Elkinton Jr. reported that multiple level of buffering linked different series of ionic exchanges which includes hydrogen, sodium, potassium, and other anions. The buffers absorb excess hydrogen and hydroxyl ions. They help in the maintenance of neutrality during redistribution of the hydrogen ion [16].

A buffer system consists of a weak acid with its conjugate base, or a weak base with its conjugate acid. Blood is a strong solution, and it has many important components that maintain the buffer systems. These include hemoglobin, bicarbonate, carbonic acid, plasma proteins, RBCs and plasma phosphate [17]. HCO3/CO2 buffer is the most important buffer system of the body, and plays a major role in regulating pH of the blood. But, the rest of the buffer systems have minimum contribution in pH regulation. In dissolved state, bicarbonate and carbon dioxide ion remains in equilibrium. Bicarbonate reduces strong acid to carbonic acid, whereas carbonic acid neutralizes strong base (Eq. (1)).

$$\text{HCO}\_2 + \text{H}\_2\text{O} \text{ << -- } \text{H}\_2\text{CO}\_3 \text{ << -- } \text{H}^+ + \text{HCO}\_3^-. \tag{1}$$

When CO2 and water is converted to HCO3 and hydrogen ions, this hydrogen ion is then buffered by hemoglobin [18].

Proteins have a buffering capacity, including hemoglobin. Protein can accept and donate H+ , if there is H+ excess or it is reduced. Hemoglobin has a distinct types of buffer action. When blood passes through the capillaries, it loses oxygen and took CO2 to raise the PaCO2 and maintain the pH. Hemoglobin plays an important role in transporting both oxygen and carbon dioxide. In 1914, Douglas, Haldane and Christiansen tried to prove that the hemoglobin binds more CO2 in the reduced form than the oxygenated form [19].

The phosphate buffer system works in the internal environment of all cells. But, in the blood H2PO4 <sup>−</sup> and HPO4 <sup>2</sup><sup>−</sup> are found in a very low concentration. Sodium dihydrogen phosphate neutralizes strong bases and sodium monohydrogen phosphate neutralizes strong acids. The Phosphate buffer system plays an important role in the kidneys.
