The rate-limiting step in the process is the first reaction, which involves the hydration or dehydration of CO2. This reaction is usually slow but is significantly sped up by the presence of carbonic anhydrase.
The second reaction, which involves the ionization of H2CO3 into H+ and HCO3−, happens almost instantaneously.
Carbonic anhydrase catalyzes the reaction involving citrate. The lungs and kidneys work together to maintain acid-base balance. The lungs eliminate CO2 (volatile acid), while the kidneys excrete acid (renal net acid excretion) equal to the net endogenous acid production (NEAP), which reflects dietary intake, cellular metabolism, and loss of acid and alkali (e.g., HCO3− loss in feces) from the body. Refer to the textbook for more details.
The Henderson-Hasselbalch equation, represented by equations 37.2 and 37.3, is used to determine how changes in CO2 and HCO3− affect pH. The amount of CO2 is calculated using the partial pressure of CO2 (PCO2) and its solubility (α) in solution. At 37°C, α has a value of 0.03. The negative logarithm of the overall dissociation constant for the reaction in equation 37.1, known as pK', has a value of 6.1 for plasma at 37°C. Alternatively, the relationship between HCO3−, CO2, and [H+] can be determined using equation 37.4.
When there are alterations in either [HCO3−] or PCO2, pH and [H+] will vary. Changes in [HCO3−] result in metabolic acid-base disorders, while changes in PCO2 lead to respiratory acid-base disorders. These disorders will be discussed further in a subsequent section. The kidneys are primarily responsible for regulating the [HCO3−] of extracellular fluid (ECF), while the lungs control PCO2.
The overall acid-base balance in the body is affected by the constituents of the diet, cellular metabolism, and the loss of alkali in feces. These processes add acid to body fluids. To maintain acid-base balance, the rate of acid excretion must match the rate of acid addition. If acid addition exceeds excretion, acidosis occurs, whereas if acid excretion exceeds addition, alkalosis occurs.
According to Figure 37.1, the main constituents of the diet are carbohydrates and fats. When there is sufficient tissue perfusion, availability of oxygen to tissues, and normal levels of insulin, carbohydrates and fats are metabolized into CO2 and H2O. This metabolic process generates 15 to 20 moles of CO2 daily. Normally, the lungs effectively eliminate this large amount of CO2 from the body, so it has no impact on acid-base balance. CO2 is referred to as volatile acid because it can potentially produce H+ after hydration with H2O. Any acid not directly derived from the hydration of CO2 is classified as nonvolatile acid, such as lactic acid.
As indicated the first reaction (hydration/dehydration of CO2) is the rate-limiting step. This normally slow reaction is greatly accelerated in the presence of carbonic anhydrase.
The second reaction, ionization of H2CO3 to H+ and HCO3 − , is virtually instantaneous.
aCarbonic anhydrase (CA) actually catalyzes the following reaction: (e.g., citrate) •Fig. 37.1 Overviewofacid-basebalance.Thelungsandkidneysworktogethertomaintainacid-basebalance.ThelungsexcreteCO2(volatileacid),andthekidneysexcreteacid(renalnetacidexcretion[RNAE])equaltonetendogenousacidproduction(NEAP),whichreflectsdietaryintake,cellularmetabolism,andlossofacidandalkali(e.g.,HCO3− lossinfeces)fromthebody.Seetextfordetails.(FromKoeppenBM,StantonBA.Renal Physiology. 5thed.Philadelphia:Elsevier;2013.)
The Henderson-Hasselbalch equation is used to quantitate how changes in CO2 and HCO3 − effect pH:
Equation 37.2
Equation 37.3 [HCO3 − ]pH = 6 1. + log 0 03. PCO2
In these equations the amount of CO2 is determined from the partial pressure of CO2 (PCO2) and its solubility (α) in solution. For plasma at 37°C, α has a value of 0.03. Also, pK′ is the negative logarithm of the overall dissociation constant for the reaction in
Eq. 37.1 and has a value for plasma at 37°C of 6.1. Alternatively the relationship between HCO3 − and CO2 on the [H+] can be determined as follows:
Equation 37.4
Inspection of Eqs. 36.3 and 36.4 show that pH and [H+] vary when either [HCO3 −] or PCO2 are altered. Disturbances of acid-base balance that result from a change in [HCO3 −] are termed metabolic acid-base disorders, whereas those resulting from a change in PCO2 are termed respiratory acid-base disorders. These disorders are considered in more detail in a subsequent section. The kidneys are primarily responsible for regulating the [HCO3 −] of ECF, whereas the lungs control the PCO2.
Overview of Acid-Base Balance
The diet of humans contains many constituents that are either acid or alkali. In addition, cellular metabolism produces acid and alkali. Finally, alkali is normally lost each day in feces. As described later, although diet dependent, the net effect of these processes is the addition of acid to body fluids. For acid-base balance to be maintained, acid must be excreted from the body at a rate equivalent to its addition. If acid addition exceeds excretion, acidosis results. Conversely, if acid excretion exceeds addition, alkalosis results.
Fig. 37.1 , the major constituents of the diet are carbohydrates and fats. When tissue perfusion is adequate, O2 is available to tissues, and insulin is present at normal levels, carbohydrates and fats are metabolized to CO2 and H2O. On a daily basis, 15 to 20 moles of CO2 are generated through this process. Normally this large quantity of CO2 is effectively eliminated from the body by the lungs. Therefore this metabolically derived CO2 has no impact on acid-base balance. CO2 is usually termed volatile acid because it has the potential to generate H+ after hydration with H2O (see
Eq. 36.1 ). Acid not derived directly from hydration of CO2 is termed nonvolatile acid (e.g., lactic acid).