The Controller and Acid-Base Physiology: An Introduction to a Complex Process

The Primary Acid-Base Disorders

There are four primary acid-base disorders that disturb normal physiology (Table 7-1). They may occur alone (simple disorders) or in combination (mixed disorders). As you will see in the next section, these acid-base processes may also occur in order to compensate for a primary abnormality. In these cases, the initial process is known as the primary disturbance, and the secondary process is known as the compensation. Two of the primary disorders (respiratory acidosis and alkalosis) are the consequence of problems with the respiratory system, and two (metabolic acidosis and alkalosis) are the consequence of problems with oxygen delivery to the tissues, abnormalities in metabolic processes, ingestion of toxins, and diseases of the kidneys. A full discussion of these disorders is beyond the scope of this book, but we will touch on the basic concepts.

Respiratory Acidosis

Respiratory acidosis is characterized by an increased P_aCO₂, a decreased pH, and ultimately, a mild increase in the serum bicarbonate concentration (remember: an increase in P_aCO₂ drives the carbonic acid reaction to the right, which results in an increase in serum bicarbonate, even before any compensation). A decrease in alveolar ventilation leads to an increase in alveolar PCO₂ and, subsequently, an increase in P_aCO₂. As we have just discussed, the increase in dissolved carbon dioxide ultimately leads to the formation of carbonic acid and a decrease in pH (Fig. 7-1).

Use Animated Figure 7-1 to play a primary respiratory acidosis and observe how the change in P_aCO₂ affects the carbonic acid equilibrium and, subsequently, the pH. The picture of the “balance” or “scale” is used to illustrate the changing equilibrium between carbonic acid and bicarbonate. In essence, this is a visual representation of the modified Henderson-Hasselbalch equation presented earlier in the chapter.

Animated Figure 7-1 (Work in progress)

Note that PCO₂ is used in this portion of the diagram as a marker for carbonic acid, as discussed previously.

The hydrogen ion produced by virtue of a respiratory acidosis cannot be buffered by bicarbonate, the primary extracellular buffer.

As the reaction shows, we would merely take a proton from the molecule of carbonic acid (producing a molecule of bicarbonate) and give it to the bicarbonate (producing a molecule of carbonic acid); there is no change in the concentration of either molecule, and no change in pH results from this exchange. Instead of relying on extracellular bicarbonate, the protons produced by respiratory acidosis must be buffered by proteins, particularly the hemoglobin in RBCs.

The bicarbonate produced by this reaction may then diffuse into the serum, resulting in an increase in the serum bicarbonate.

An increase in P_aCO₂ (i.e., hypoventilation) can result from problems with the controller, ventilatory pump, or gas exchanger. For example, a person who attempts to commit suicide by taking an overdose of a sedative medication that depresses the ventilatory controller will develop respiratory acidosis. Mild to moderate derangements in the ventilatory pump or gas exchanger, such as seen in individuals with mild asthma, typically do not cause a respiratory acidosis by themselves because the controller responds to the accumulation of carbon dioxide and hydrogen ions by increasing ventilation and restoring a normal or near-normal P_aCO₂. On the other hand, depression of the controller is associated with respiratory acidosis, even in the presence of a normal ventilatory pump and gas exchanger.

In the setting of a normal controller, severe abnormalities of the gas exchanger or ventilatory pump may lead to hypercapnia and respiratory acidosis because maximal achievable ventilation under these conditions may not be adequate to achieve alveolar ventilation sufficient to meet the carbon dioxide production associated with the metabolic state of the person. A person with severe emphysema and acute pneumonia, for example, may develop hypercapnia despite the best efforts of the controller to increase ventilation.

Respiratory Alkalosis

Respiratory alkalosis is characterized by a decreased P_aCO₂, an increased pH, and a mild decrease in the serum bicarbonate concentration. An increase in alveolar ventilation leads to a decrease in alveolar PCO₂ and subsequently a decrease in P_aCO₂. The decreased P_aCO₂ drives the carbonic acid-carbon dioxide equilibrium to the left (see equation in the Definitions section); the hydrogen ion concentration decreases and pH increases (Fig. 7-2).

Use Animated Figure 7-2 to play a primary respiratory alkalosis and observe how the change in P_aCO₂ affects the carbonic acid equilibrium and subsequently the pH.

Animated Figure 7-2 (Work in progress)

Because one would expect the decrease in P_aCO₂ and the increase in pH to reduce the activity of the respiratory centers in the brainstem, the presence of a primary respiratory alkalosis suggests that other sources of information or stimuli are affecting the controller. Patients with mild, acute asthma attacks, for example, may be short of breath and anxious and experience stimulation of pulmonary receptors as a consequence of the bronchospasm and inflammation of the airways. All of these factors can contribute to an increase in ventilation and produce the respiratory alkalosis that is typical of this condition.

Metabolic Acidosis

Metabolic acidosis is characterized by a reduced bicarbonate concentration and a low pH. It is generally accompanied by compensatory hyperventilation. Metabolic acidosis is typically the consequence of the accumulation of fixed acids in the body (e.g., caused by renal failure, accumulation of lactic acid from anaerobic metabolism, or ingestion of toxins) or the loss of bicarbonate from the kidneys or gastrointestinal (GI) tract (e.g., as is seen with diseases of the renal tubule or profuse diarrhea). As fixed acids accumulate, they are initially buffered by bicarbonate, lowering the bicarbonate concentration (Fig. 7-3).

Use Animated Figure 7-3 to play a primary metabolic acidosis and observe how the change in bicarbonate affects the carbonic acid equilibrium and subsequently the pH (shown before respiratory compensation). The presence of an increased hydrogen ion concentration stimulates the chemoreceptors, increasing ventilation and leading to a decrease in P_aCO₂ and further buffering of the acid (a process that is one of the compensatory mechanisms discussed later in this chapter).

Animated Figure 7-3 (Work in progress)

The physiologic derangements that lead to metabolic acidosis can be subdivided into two major categories: those that lead to an elevated anion gap (referred to as anion gap acidoses) and those that are not associated with an elevated gap (referred to as non-anion gap acidoses). The anion gap is the difference in concentrations between the commonly measured anions and cations in the blood. It can be altered by certain acids, so calculation of this difference serves as an aid to recognition and diagnosis of metabolic acidosis. The chemicals in the blood must maintain electrical neutrality, and the cations (positively charged ions) such as sodium, potassium, calcium, and magnesium are balanced by anions (negatively charged molecules) such as chloride, bicarbonate, proteins, sulfates, and phosphates.

The anion gap is the difference between the concentration of the major cation, sodium, and the anions that we routinely measure, chloride and bicarbonate (Fig. 7-4).

A normal anion gap is between 5 and 11 meq/L (note: some people calculate the anion gap by including potassium as one of the cations; in this case, the normal values for the gap are between 9 and 15 meq/L). A significant portion of the anion gap is composed of the negatively charged proteins such as albumin. Therefore, when we speak of a “normal” range for the anion gap, we are assuming a normal level of albumin. If the serum albumin is low, as is seen in malnourished individuals and in people who have disease in which albumin is lost from the urine, the normal range for the anion gap must be adjusted downward (2.5 meq/L for every 1 g/dL decline in the serum albumin concentration).

A limited number of conditions produce an anion gap acidosis, including renal failure (in which reduced filtration capability of the kidney leads to the accumulation of sulfates and phosphates from the metabolism of proteins), hypoperfusion of tissues leading to lactic acid accumulation, uncontrolled diabetes leading to ketoacidosis, and the ingestion of drugs such as aspirin and toxins such as ethylene glycol. Although the respiratory system can compensate, to a degree, for the change in hydrogen ion concentration that results from these processes, elimination of the unmeasured anions requires a functioning kidney.

Non-anion gap acidosis is most commonly caused by conditions associated with a loss of bicarbonate from the body. The classical clinical example of this is moderate to severe diarrhea (the fluid lost from the GI tract has a high concentration of bicarbonate). Disorders of the kidney, such as renal tubular acidosis, are also characterized by non-anion gap acidosis.

Metabolic Alkalosis

Metabolic alkalosis is characterized by an increased bicarbonate concentration and an elevated pH (Fig. 7-5).

Use Animated Figure 7-5 to play a primary metabolic alkalosis and observe how the elevation in bicarbonate concentration affects the carbonic acid equilibrium and subsequently the pH (shown before respiratory compensation).

Animated Figure 7-5 (Work in progress)

This disorder is generally accompanied by compensatory hypoventilation. Metabolic alkalosis is often the consequence of loss of hydrogen ion from the GI system (e.g., as is seen with prolonged vomiting). It is also seen in association with diuretic therapy, with contraction of the total amount of fluid in the body and loss of potassium from the blood, as well as with the intake of excessive bicarbonate (as seen with the use of antacids). For metabolic alkalosis in general, as the pH increases, stimulation of the chemoreceptors is reduced, and hypoventilation generally follows.