Net Bicarbonate or Bicarbonate Precursor Addition to Extracellular Fluid

HCO- administration or addition of substances whose metabolism generates HCO- (eg, lactate, citrate) at a rate greater than that of metabolic H+ production also leads to an increase in ECF [HCO-]. In the presence of normal kidney function, however, ECF [HCO] will not increase significantly. This occurs because as serum [HCO] exceeds the plasma threshold for HCO reabsorption, the kidney excretes the excess HCO. As a result serum bicarbonate will not rise unless there is a change in renal bicarbonate handling (maintenance factor). The need for maintenance factors in the pathogenesis of metabolic alkalosis is discussed in more detail below.

Loss of Fluid from the Body That Contains Chloride in Greater Concentration and Bicarbonate in Lower Concentration Than Serum

If this type of fluid is lost, ECF volume must contract. If this contraction is substantial enough, a measurable increase in serum [HCO] develops. Protons are not lost in this setting in contrast to losses noted with vomiting or nasogastric suction. Bicarbonate is now distributed in a smaller volume, resulting in an absolute increase in ECF [HCO]. This is referred to as contraction alkalosis.

  • 1. Metabolic alkalosis is a systemic disorder characterized by increased pH as a result of a primary increase in serum bicarbonate concentration.
  • 2. Primary elevation of serum bicarbonate concentration is caused by net H+ loss or net addition of bicarbonate precursors to the ECF.

The first line of pH defense during metabolic alkalosis is, again, buffering. When HCO is added to ECF, protons react with some of this HCO to produce CO2 that is normally exhaled by the lungs. Through this chemical reaction, the increase in serum and ECF [HCO] is attenuated. It has been shown that the intracellular fluid (ICF) contributes the majority of H+ used in this buffering process.

Respiratory compensation also occurs with metabolic alkalosis. Under normal conditions, control of ventilation occurs in the brainstem and is most sensitive to interstitial H+ concentration (see Chapter 9). Respiratory compensation to metabolic alkalosis follows the same principles as respiratory compensation to metabolic acidosis. Of course, the direction of the change of partial pressure of arterial carbon dioxide (PaCO2) is different (ie, hypercapnia as a result of hypoventilation rather than hypocapnia as a result of hyperventilation occurs) and constraints regarding oxygenation must limit the magnitude of this hypoventilatory response. With metabolic alkalosis, the PaCO2 should increase 0.6 to 1.0 times the increase in serum [HCO-]. Absence of compensation in the setting of metabolic alkalosis constitutes the coexistence of a secondary respiratory disturbance.

The third line of defense is renal excretion. This can be described as follows: The normal kidney has a powerful protective mechanism against the development of significant increases in ECF [HCO-], namely the plasma threshold for [HCO-], above which proximal reabsorption fails and HCO- losses in urine begin. Mathematically, the plasma [HCO-] can be estimated at a given time following addition of HCO- to the body by:

where [HCO-] is the plasma bicarbonate at time t, [HCO-]PT is the plasma threshold for bicarbonate, [HCO-]M is the bicarbonate concentration after adding bicarbonate to the body, GFR is the glomerular filtration rate, Vd is the volume of distribution for bicarbonate, and exp is the exponential function.

In nonmathematical terms, once the plasma threshold (PT) is exceeded, bicarbonate excretion in urine is proportional to the glomerular filtration rate (GFR). If a patient has a GFR of 100 mL/min and the bicarbonate concentration is 10 mEq/L above the PT, bicarbonate will be lost in the urine initially at a rate of 1 mEq/min! Therefore, the corrective response by the kidney to excrete excessive HCO- in urine usually corrects metabolic alkalosis unless there is a maintenance factor that prevents this. Exceptions to this rule occur when renal function is dramatically impaired and/or when the ongoing alkali load truly overwhelms the renal capacity for bicarbonate elimination. These exceptional situations are both uncommon and easily identified. Therefore, we usually approach the pathophysiology of metabolic alkalosis by addressing initiation factors (ie, factors that initiate the process) and maintenance factors (those that prevent renal excretion of excess bicarbonate). In some cases, as will be seen, the same factor may be responsible for both initiation and maintenance.

The importance of maintenance factors in the pathophysiology of metabolic alkalosis

FIGURE 8-1. The importance of maintenance factors in the pathophysiology of metabolic alkalosis. In this figure, we see that proton loss (eg, from vomiting) leads to increases in pH and [HCO3]. These increases in [HCO3] are accompanied by increases in HCO3 filtration and loss in urine. If a maintenance factor (eg, volume depletion, primary mineralocor- ticoid excess) is present, however, that raises the tubular transport of HCO3 (Tmax), increased renal losses of HCO3 are prevented, and metabolic alkalosis is maintained. Note that the higher pH causes a decrease in alveolar ventilation (VA; see Chapter 9) and the PaCO2 increases.

  • 1. The first line of defense is buffering. When HCO3 is added to ECF, H+ reacts with HCO3 to produce CO2 that is normally exhaled in expired gas. Most of the H+ used in this buffering comes from the ICF.
  • 2. A rise in PaCO2 is the normal compensatory response to simple metabolic alkalosis.
  • 3. In virtually all cases of metabolic alkalosis, the kidney participates in the pathogenesis by not excreting the excess bicarbonate.

A number of factors increase the apparent tubular maximum concentration (Tmax) for HCO-. As a result, they increase net HCO- reabsorption by the kidney. Figure 8.1 shows this schematically.

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