Acid-Base

Ion trapping, pKa and the Henderson–Hasselbalch equation –

What’s the pH value?
Let’s start off with the pH value. The pH value is a measure of free
hydrogen (H+) ions on a negative log scale. So, basically what that means
is that it’s a measure of the acid load in the body.
What does this mean?

• pH increases when hydrogen ion concentration decreases (alkalosis).
• pH decreases when hydrogen ion concentration increases (acidosis).
  If the pH is 7.4, this means that the concentration of free hydrogen ions
  is 10-7.4

Pathological pH values and corresponding hydrogen ion concentrations
The correct concentration of hydrogen ions in the body is key for life, and it’s regulated in a very narrow range. If the concentration of hydrogen ions is less than 36 nmol / L, the serum pH will rise above 7.44 and this is a called alkalosis.
If the concentration of free hydrogen ions is greater than 44 nmol / L, the serum pH falls below 7.36 and this is called acidosis.

Free hydrogen ions are very reactive and can bind to negatively charged proteins, changing their conformational structure and making them less functional. This is why the body needs to maintain the pH in a very narrow range (7.36–7.44).

For example, the enzymatic capacity of lactate dehydrogenase is dependent upon pH. Lactate dehydrogenase is an enzyme that converts lactate to pyruvate and vice versa, and it functions most efficiently around a pH of 7.4

Why is this narrow pH range important?
The body needs to maintain pH in a very narrow range in order for enzymes to work efficiently. This capacity is really impressive, especially if you consider the amount of hydrogen ions produced in the body. The net acid production in the body is in the range of 100 mmol / day,
and the concentration of free hydrogen ions is in the range of 40 nmol. In order to maintain this huge gradient, the hydrogen ions need to be buffered and excreted from the body.

The enzyme that catalyzes this reaction is called carbonic anhydrase. It catalyzes the reaction of three hydrogens with bicarbonate (HCO3-) and its transformation into water (H2O) and carbon dioxide.

Bicarbonate—the primary buffer

What happens when acid is introduced into the body? Well, buffers take care of it. Buffers act like sponges, taking up hydrogen ions when there is too much and releasing hydrogen ionswhen there is too little. Examples of buffers in the body include hemoglobin, bicarbonate, phosphate, and bone. When it comes to buffering, 60% happens intracellularly and 40% happens extracellularly. The most important buffer in the extracellular space is bicarbonate. What happens when acid is added into the body?

In metabolic acidosis, there’s an excess of hydrogen ions. What happens to these hydrogen ions? They combine with bicarbonate in order to form carbonic acid (H2CO3). So, as hydrogen ions increase, bicarbonate decreases.

What happens to the carbon dioxide? As you might already know, it is eliminated and exhaled through the lungs. We can adjust carbon dioxide elimination through hyper and
hypoventilation. When the patient is hypoventilating, carbon dioxide is accumulating and combines with water to form carbonic acid, which then dissociates into H+ and bicarbonate. So, H+ will increase in hypoventilation, and the pH will consequently drop.

The normal values and cutoffs

Next, let’s talk about the normal values. As mentioned, the serum normal range for pH is 7.35 to 7.45, but for convenience purposes, we typically refer to normal serum pH as 7.4. Whenever pH is lower than 7.4, we say it’s acidemic and whenever it’s higher, we say it’s alkalinic. The hydrogen ion concentration that corresponds to this pH range is 35 to 45 nmol / L. The normal range of bicarbonate is 22–26 mmol / L, but for convenience purposes, we typically quote 24 mmol / L as normal. The normal range for the partial pressure of carbon dioxide (PCO2) is
35–45 mmHg. Again, for convenience purposes, 40 mmHg is referred to as a normal PCO2
value.

The Henderson-Hasselbalch equation made easy

The Henderson-Hasselbalch equation can help you to understand the
relationship between pH, bicarbonate, and PCO2.

It’s critical to understand how the pH changes when the bicarbonate or PCO2 goes up or down, how the PCO2 compensates for a rise or fall in bicarbonate, and how the bicarbonate tries to compensate for a rise or fall in the PCO2. In order to understand these mechanisms, we can make the equation much simpler. Since we only want to understand the relationship between the pH, bicarbonate, and PCO2, we can get rid of the negative logarithm of the acid dissociation constant (pKa) and the log. It’s not an equation anymore, but just shows how the pH corresponds to bicarbonate and PCO2.

So, when there’s respiratory acidosis and the patient hypoventilates, the PCO2 will rise, which will in turn cause the pH to fall. When the patient hyperventilates and the PCO2 falls, the pH will increase and we call that respiratory alkalosis.

Similarly, when the bicarbonate falls due to metabolic acidosis, the pH will fall as well. And when the bicarbonate goes up as in metabolic alkalosis, the pH will also go up.

Compensation—the basics

Next, let’s summarize how the metabolic system (in other words, the kidneys) tries to compensate for a respiratory problem, and how the lungs compensate for a metabolic problem. Note that it usually takes hours to days for the kidneys to react to respiratory problems, while the lungs react much more quickly to metabolic problems.

So, what happens when there are metabolic problems?

When there are metabolic problems, the lungs try to compensate. This
compensation is fast, and two scenarios are possible:

1. Metabolic acidosis
2. Metabolic alkalosis

Metabolic acidosis

When bicarbonate levels drop, pH will also go down, and we call that scenario metabolic acidosis. What would the lungs have to do in order to normalize the pH? Well, if the bicarbonate goes down, the PCO2 would also have to go down in order for the pH to stay constant. And that’s exactly what happens in respiratory compensation. The lungs hyperventilate, the PCO2
goes down, and the pH is corrected so that it’s not as low as it would be without respiratory compensation. To summarize, in metabolic acidosis, the lungs hyperventilate, making
PCO2 go down and slightly increasing pH.

Metabolic alkalosis

What happens when bicarbonate goes up? Since the pH equals bicarbonate divided by PCO2 , when bicarbonate goes up, the pH will also go up. We call this metabolic alkalosis. And what do the lungs do to compensate for this rise in bicarbonate (i.e., what would be the respiratory compensation?) Well, the lungs have to increase the PCO2, which they do through hypoventilation. As the PCO2 rises, the pH is corrected so it’s not as high as it was before respiratory compensation.

To summarize, in metabolic alkalosis, the lungs hypoventilate, making PCO2 go up and slightly decreasing pH.

What happens when there are respiratory problems?

When there are respiratory problems, the kidneys try to compensate. This
compensation occurs much slower, and two scenarios are possible:

1. Respiratory acidosis
2. Respiratory alkalosis

Respiratory acidosis

In respiratory acidosis, hypoventilation has resulted in an increased PCO2, which has caused pH to go down. The kidneys will compensate by increasing the bicarbonate level to bring the pH up. Since the kidneys take a long time to react, the bicarbonate will increase only a little bit in the acute setting and the pH will remain somewhat low. In chronic settings, bicarbonate will have more time to increase and the pH will rise more than it does in the acute setting.

Respiratory alkalosis

In respiratory alkalosis, hyperventilation has resulted in a decreased PCO2, which has caused pH to go up. The kidneys will compensate by decreasing the bicarbonate level. Again, in the acute setting, the bicarbonate will only decrease a little bit because the kidneys will not have had enough time to fully compensate, and the pH will remain somewhat high. In chronic respiratory alkalosis, bicarbonate will have more time to decrease, permitting the pH to reach levels that are
closer to normal.

So, there are actually four possible scenarios with respiratory problems:

1. Acute metabolic compensation for respiratory acidosis:
   – kidneys try to increase bicarbonate levels (bicarbonate retention), but bicarbonate only increases slightly and pH remains low
2. Chronic metabolic compensation for respiratory acidosis:
   – bicarbonate has more time to increase, so pH will be closer to normal
3. Acute metabolic compensation for respiratory alkalosis:
   – kidneys try to decrease the bicarbonate level through bicarbonate secretion, but bicarbonate only decreases slightly, so pH remains high
4. Chronic metabolic compensation for respiratory alkalosis:
   – bicarbonate has more time to increase, so pH will be closer to normal

Why compensation is never complete

Compensation will never normalize the pH. In fact, compensation is triggered by an abnormal pH.
If compensation succeeded in completely normalizing the pH, then compensation would stop. In other words, the compensation feedback loop would stop, which would then lead to an abnormal pH again, assuming that the primary acid-base problem that led to compensation in
the first place was still present. What happens instead in compensation is the pH adjusts a little bit, but it still stays abnormal. Since it is still abnormal, the compensation feedback loop continues, and the lungs continue to hyper or hypoventilate, which results in a continued raising or lowering of the pH.

A simple rule for identifying the type of acid-base disorder

Acid-based problems can occur isolated or in combination. But, even if they’re combined, there’s usually a primary problem that’s most pronounced.

So, how you can tell if the primary problem is metabolic or respiratory in nature?

There’s a simple rule for identifying the primary acid-base problem:

• With respiratory problems, PCO2 and pH change in different directions
• With metabolic problems, PCO2 and pH change in the same direction