Acid-Base Balance

Acid-Base Balance Learning Objectives

• Define pH and the factors that determine blood pH

• Explain how the carbonic acid-bicarbonate system is affected by the renal and respiratory systems. 

  • • Differentiate between compensation and correction

• Define and compare acid-base imbalances

  • • Explain causes and describe how each of these imbalances alters normal physiology

• Explain in detail how pH compensation and pH correction occur for each of the 4 primary pH imbalances. 

  • • List expected pH, carbon dioxide, and bicarbonate for metabolic disorders that have been compensated

• Analyze data and predict whether a person has acidosis or alkalosis (metabolic or respiratory)

Buffer Systems

Review of Buffer Systems

Buffer systems are composed of chemicals that maintain a constant pH (they are able to resist changes to pH). Buffer systems can be made in a beaker in a chemistry or biology laboratory. We are concerned, however, with buffer systems that are found in the human body.

A buffer system has the ability to absorb H+ (protons) or release H+ (protons) so that the pH doesn't change. It does this by having both a weak acid and its conjugate (related) base.

Think back to what was discussed in Chapter 2. 

• • What happens to the intracellular pH when cells are subjected to hypoxia? Why is the pH change detrimental to cells? 

Without buffers, all of the proteins in our body (including all of our enzymes) would undergo conformational (shape) changes — they would denature, and thus lose their function. The normal pH of blood is approximately 7.4, slightly alkaline. A pH of 6.8 is lethal. Buffers are our friend. They help our body maintain a constant pH even when a strong acid or base is added in small quantities.

In the human body, there are buffer systems that maintain intracellular and extracellular pH.

Buffers have limitations, however. If too much acid or base is added to a buffered solution, the pH will change. The pH change won't be nearly as drastic as long as the solution is buffered. You'll be learning about four different pH imbalances that are commonly seen.

Buffer Systems in the Human Body

Carbonic acid — bicarbonate system

The primary buffer system in extracellular fluid is the carbonic acid — bicarbonate system.

Hopefully, you've seen this equation before, most likely in physiology class and in chemistry class. This equation represents the equilibrium of the carbonic acid — bicarbonate system. In order, the chemicals in this equation are:

Carbon dioxide, water, carbonic acid (a weak acid), hydrogen, and bicarbonate (the conjugate base of carbonic acid). 

CO2    +  H2O  <=>  H2CO3 <=>    H+  +   HCO3- 

The importance of this equation is the ratio of two molecules, bicarbonate (HCO3-) and carbonic acid (H2CO3). Below is a short video that provides an overview of the role of CO2  and HCO3-.

• • • The normal ratio of HCO3-/ H2CO3  is 20:1. At that ratio the pH = 7.4.

    • Because it's important for blood pH to remain at 7.4, the body works hard to maintain that 20:1 ratio.

Let's look next at how the body is able to regulate these two components of this buffer system.

The normal ratio of HCO3-/ H2CO3  is 20:1. At that ratio the pH = 7.4.

Because it's important for blood pH to remain at 7.4, the body works hard to maintain that 20:1 ratio.

Let's look next at how the body is able to regulate these two components of this buffer system.

Both carbon dioxide and carbonic acid are regulated by the lungs and respiration rate. Remember, when you think of carbon dioxide, think of acid.

If respiration rate increases does the amount of CO2  increase or decrease in the blood? A:

That means that the lungs regulate blood pH!

Bicarbonate, on the other hand, is regulated by the kidneys. The kidneys can regulate the amount of bicarbonate retained by the body.

Bicarbonate is filtered and then reabsorbed back into the blood. The factor that most determines how much bicarbonate is reabsorbed is the amount of H+ that is secreted. That's because the bicarbonate has to bind with H+ in order to be reabsorbed.

Anything that increases H+ secretion will increase bicarbonate reabsorption.

• • • •  As bicarbonate levels in the blood increase, blood pH  increases (becomes more basic).

      •  As bicarbonate levels in the blood decrease, blood pH decreases (becomes more acidic). 

• • • • • Thinking Questions: Aldosterone increases H+ secretion. Does aldosterone, therefore, increase or decrease bicarbonate levels in the blood? What about blood pH, how does that change? A:

The Phosphate buffer system  

One of the fluids in the body that is buffered with phosphate is urine. Good thing urine is buffered; otherwise the pH of urine would become very low. The normal pH of urine is about 6.0, which is slightly acidic. Without buffers, urine pH could become much lower. Sounds painful!

The phosphate ion can either accept or release H+, which will allow pH to remain unchanged. 

pH Imbalances

pH imbalances fall into two categories, those that are metabolic in nature and those that are respiratory.

1. Metabolic pH imbalances

• • • Cause: Changes in pH due to relative changes in bicarbonate levels in the blood

2. Respiratory pH imbalances 

• • • Cause: Changes in pH due to changes in CO2 /carbonic acid. 

      •  Remember, when you think of CO2 , think of carbonic acid.

We will start with a case study on pH imbalances: 

Metabolic pH Imbalances

Let's look at the two types of metabolic pH imbalances:

Metabolic Acidosis 

Acidosis is the process of blood pH dropping below the normal range (7.35-7.45), referred to as acidemia (remember the suffix "emia" always refers to blood). By definition, acidemia is pH < 7.35. This results when:

The concentration of H+ in the blood is increased. H+ goes up, pH goes down — an inverse relationship.

The concentration of bicarbonate in the blood is decreased. Bicarbonate goes down, pH goes down — a direct relationship.

Causes of metablic acidosis

• • • Increases in non-carbonic acids (so not from excess CO2) such as lactic acid or ketones (from excessive fat degradation).  

      • • Under what circumstances would the body produce lactic acid? A:

        • Increases in non-carbonic acids can also result from ingestion of substances that are acidic. For example, an aspirin overdoes. The active ingredient in aspirin is salicylic acid. Ingestion of anti-freeze also causes metabolic acidosis.    

• • • Excessive loss of bicarbonate

      • • Sodium bicarbonate is made by the pancreas and is secreted into the small intestine. The function of the sodium bicarbonate is to neutralize stomach acid. Normally, the bicarbonate is absorbed through the wall of the large intestine and enters the blood.

        • However, if an individual has inflammation of the large intestine that results in diarrhea, the bicarbonate is lost with feces. Excessive diarrhea causes excessive loss of bicarbonate. The result is metabolic acidosis.                                                                                .     

• • • Decreased H+ secretion  

      • • Decreased aldosterone secretion results in decreased H+ secretion. Consequently, H+ accumulates in the blood and pH drops.

        • Renal failure also causes metabolic acidosis. In end-stage renal failure, kidney function is lost. Normally, H+ are secreted from the blood and into filtrate. In the absence of kidney function, H+ is not secreted, accumulates in the blood and the pH of blood drops.

Responses to metabolic acidosis

There are three different responses to this pH change.

1.  H+/K+ shift

• • • Some of the excessive H+ ions shift into the ICF from the ECF to be buffered by intracellular proteins. To equalize the charges, K+ ions shift out of the ICF and into the ECF. 

      • What electrolyte imbalance might result from this? A:  

2. Respiratory compensation

• • Metabolic pH imbalances are compensated for by the respiratory system.

  • The normal ratio of bicarbonate to carbonic acid is 20:1, and at that ratio the pH is 7.4

  • With metabolic acidosis, the concentration of bicarbonate has decreased relative to carbonic acid.

  • The goal of compensation is to restore the 20:1 ratio even though the values for bicarbonate and carbonic acid will not be normal.    

    • • That means the body will decrease carbonic acid levels in the body so that a 20:1 ratio of bicarbonate; carbonic acid can be achieved.

  • With the restoration of this ratio, the blood pH will be normal, even though the values for bicarbonate and carbonic acid will not be normal.

  • So, how can the body decrease carbonic acid levels?                                                                     

    • • Remember that carbonic acid ≃  CO2

      • The respiratory system can control the amount of CO2 and thus alter the amount of carbonic acid.

      • Respiratory compensation, then, in response to metabolic acidosis is increased respiration, in order to "blow off" more CO2.

        • There is a special name for this type of respiration — it's call Kussmaul Respiration.

3. renal correction

• • The third and final response is renal correction. 

    • The goal of correction is to return the values for both bicarbonate and carbonic acid to normal.

    • With correction, not only is the pH returned to normal, due to the restoration of the 20:1 ratio of bicarbonate and carbonic acid levels, but the value for each is returned to normal. Unlike with compensation, if you were to measure bicarbonate levels in the blood, they would be normal.

    • To correct the imbalance, the kidneys will secrete more H+ and reabsorb more bicarbonate. 

      • • If metabolic acidosis is from lactic acid accumulation, for example, the kidneys will correct by secreting H+ and reabsorbing bicarbonate.

        • Sometimes renal correction is not possible. If for example the kidneys have failed, renal correction can not be achieved.

    • The respiratory system cannot correct the metabolic pH imbalance because is can only affect the carbonic acid levels, and cannot return the bicarbonate levels to normal, only the renal system can do this. Instead, the respiratory system compensates for the metabolic imbalance by trying to restore the ratio of carbonic acid to bicarbonate.

Clinical features of metabolic acidosis

• 1. Kussmaul respirations

  2. cardiac dysrhythmias from hyperkalemia

  3. neurological changes: lethargy, coma, generalized depression of the central nervous system.

     • These neurological changes are the result of changes in enzyme activity related to the change in pH

Metabolic Alkalosis

• • • By definition, blood pH > 7.45.

    • Bicarbonate levels in the blood are increased above normal.

    • H+ in the blood is decreased.

Causes of metabolic alkalosis

In general, metabolic alkalosis is caused by either excessive loss of H+ or excessive retention of bicarbonate.

• • Specific causes include:

    • • GI losses of H+ from vomiting or nasogastric suctioning. The stomach, of course contains HCl, hydrochloric acid. With vomiting, stomach acid is lost.

      • Excessive amounts of aldosterone. Any disease or condition that causes the release of aldosterone can potentially result in metabolic alkalosis. Aldosterone increases H+ secretion, so that H+ is lost in the urine. 

        • • What might cause excess aldosterone secretion? 

          • Anything that decreases renal profusion, including disease processes involving the heart or diseases or conditions that cause excessive fluid loss.

          • In addition, the excessive H+ secretion also promotes excessive reabsorption of bicarbonate back into the blood.

Responses to Metabolic Alkalosis

The body's response to metabolic alkalosis is the opposite of the response to metabolic acidosis.

1. H+/K+ shift

• • With metabolic alkalosis, there are too few H+ in the ECF. So, H+ ions shift out of cells and into the ECF. In exchange, K+ ions shift out of the ECF and into cells (ICF). Sketch out this process to help you visualize this exchange.

    • • What type of electrolyte imbalance might result from this H+/K+ shift? A:

2. Respiratory compensation

• • As with metabolic acidosis, the respiratory system compensates for metabolic alkalosis.

    • Remember that compensation, by definition, is the restoration of the 20:1 ratio of bicarbonate to carbonic acid, but the values of each are not normal. Once the 20:1 ratio is returned, the pH will be normal.

    • With metabolic alkalosis, the level of bicarbonate in the blood has increased.

    • Therefore, the amount of carbonic acid in the blood must increase as well to restore the 20:1 ratio. This is achieved via slow, shallow respirations.

3. Renal correction

• • As with metabolic acidosis, the kidneys correct for metabolic alkalosis. Because there are too few H+ ions in the blood, the body needs to conserve H+. Therefore, H+ secretion by the renal tubules decreases.

    • • If H+ secretion decreases, how is bicarbonate reabsorption affected? A:

Clinical features of metabolic alkalosis

• 1. slow, shallow respirations

  2. cardiac dysrhythmias from hypokalemia

  3. generalized muscle weakness from hypokalemia

  4. seizures from increased excitation of the CNS (central nervous system)

Respiratory pH imbalances

There are two of them, respiratory acidosis and respiratory alkalosis. These are distinguished from the metabolic pH imbalances by the fact that both of these are the result of changes in CO2 and thus carbonic acid.

Respiratory acidosis

• • This pH imbalance is characterized by the following:

    • • pH < 7.35

      • increased pCO2 (hypercapnia) and increased carbonic acid.

      • H+ in the blood is increased

Causes of respiratory acidosis

In general, this pH is caused by poor ventilation of alveoli.

• • Specific causes include:

    • • Depression of the respiratory center in the brainstem (brainstem trauma, over-sedation)

      • Respiratory muscle paralysis

      • Chest wall disorders

      • Various lung disorders and conditions including diseases such as chronic bronchitis, emphysema, pulmonary edema

        • We will return to respiratory acidosis later on the semester during the chapter on pulmonary diseases. In the image, you can see that in bronchitis, airways are narrowed, which prevents normal ventilation of alveoli. This impaired ventilation leads to increased CO2 and thus increased carbonic acid, causing respiratory acidosis.

Responses to respiratory acidosis

The responses are similar to those seen with metabolic pH imbalances, but there are differences.

1. H+/K+ shift

• • With a respiratory acidosis, there are too many H+ ions in the ECF. 

    • • Will H+ move into the ICF or the ECF? 

      • Will hyperkalemia or hypokalemia result? Why? 

      • A:

2. Renal compensation

• • With respiratory pH imbalances, the kidneys compensate. The goal, as usual of compensation, is to achieve a 20:1 ratio of bicarbonate to carbonic acid.

  • This pH imbalance is the result of increased CO2 and H2CO3 (carbonic acid). The compensation, therefore, must increase HCO3-  (bicarbonate) in order to achieve the 20:1 ratio.

  • The kidneys regulate bicarbonate. That means that the kidneys must increase the amount of bicarbonate in the blood, which they do by increasing reabsorption of bicarbonate from the filtrate into the blood. Simultaneously, H+ secretion is increased, which also helps to decrease blood pH.

  • In the image below, you can see HCO3- , which is in the lumen of the renal tubule, moves (in a very complicated way) into the capillary. H+ moves from the renal tubule cell into the lumen of the renal tubule.

3. Respiratory correction

• Respiratory pH imbalances are corrected by the lungs. The respiratory system will restore CO2 levels to normal, if possible.

  • Keep in mind that with some chronic pulmonary disorders, such as chronic bronchitis, respiratory correction never occurs. Individuals with chronic pulmonary disorders may live for years with compensated pH imbalances (but not corrected).

• But, if normal pulmonary function is restored, the goal of correction is to bring carbonic acid back to normal. 

  • Would increased or decreased respiration result in the restoration of normal carbonic acid levels? A:

Clinical manifestations of respiratory acidosis

The clinical manifestations are often those of the underlying disorder. Mild to moderate hypercapnia that develops slowly usually has minimal symptoms. Patients may be anxious and may complain of shortness of breath. As the hypercapnia becomes worse, anxiety increases and the patients become more confused and somnolent (sleepy, drowsy, lethargic).

Respiratory Alkalosis 

The pH imbalance is characterized by the following:

• • • • pH > 7.45

      • Decreased pCO2 (hypocapnia) and decreased carbonic acid.

      • H+ in the blood is decreased.

Causes of respiratory alkalosis

In general, this pH imbalance is caused by alveolar hyperventilation.

Most commonly, specific causes are:

• • • • hypermetabolic states from elevated body temperature

      • emotional stress - anxiety

      • increased altitude, where decreased oxygen in the atmosphere can result in hyperventilation

      • Improper use of mechanical ventilators (inappropriate settings resulting in increased breathing rate)

Responses to respiratory alkalosis

There are three response that result from respiratory alkalosis.

1. H+/K+ shift 

Try this one on your own. Remember that there are not enough H+ ions in the blood (leading to an alkalosis).

2. Renal compensation

• • In some cases of respiratory alkalosis, renal compensation doesn't occur because it takes 2 or 3 days for it to be effective. In the case of an anxiety attack, the most common cause of respiratory alkalosis, the pH is quickly corrected when normal respiration returns.

  • However, renal compensation is important for ongoing hyperventilation, as might occur with elevated body temperature.

  • Renal compensation involves the body retaining H+ and decreasing bicarbonate reabsorption. The hyperventilation decreases carbonic acid, so compensation for this must decrease bicarbonate levels in the blood in order to achieve the 20:1 ratio.

3. Respiratory Correction

• • Correction is achieved via the restoration of normal respiration. As ventilation of alveoli slows, carbonic acid levels increase and return to normal.

Clinical manifestations of respiratory alkalosis

Metabolic alkalosis is characterized by dizziness, tingling sensations in extremities, and the face. Eventually, seizures can occur.

How to interpret acid-base disturbances

What do you do with Arterial Blood Gas (ABG) information such as this?:

• • • • pH = 7.5 (normal is...?)

      • pCO2 = 30 mm Hg (normal is 38-44)

      • pO2 = 85 mm Hg (normal is 75-100)

      • [HCO3-] = 24 meq/liter (normal is 22-26)

There are two questions we can address here. One is, what type of acid-base imbalance (if any) is occurring with this patient? And second, is there evidence that the body is compensating for this imbalance?

Where do we begin? Well, if there is an acid-base imbalance, we would expect the pH to be affected. So the first thing to look at is the pH value. Is a pH of 7.5 above or below the normal blood pH range? 

Since it is above the normal range, there is an alkalosis occurring. 

Now we can look further into the data to determine whether the cause is metabolic or respiratory. Which values do we need to look at to determine this? 

Remember, for pH, we are concerned with the ratio between carbonic acid and bicarbonate, but also that CO2 is going to be the source of our carbonic acid. So look to the values for pCO2 and HCO3-.  Why aren't we looking at O2? What role does O2 play in determining pH? 

Trick question — O2 does not determine pH! However, there may be instances where the pO2 reading might tell us something about the function of the respiratory system that could be useful, but we will come back to that later.

Okay, we know we need to look at pCO2 and HCO3-. What are these values telling us? 

Well, since HCO3- is in the normal range, let us hypothesize that this is not the cause of our pH imbalance, but rather the lower than normal pCO2 is the culprit. To check if this makes sense, ask yourself, does a low pCO2 lead to a high pH? 

Well, if there is less CO2, what does that mean for carbonic acid? If there is less carbonic acid, what does that mean for pH? So, yes, in this case the low pCO2 can be the cause of the alkalosis, making this a respiratory alkalosis.

How do we determine if there is evidence of compensation? If it is a respiratory alkalosis, where would we find evidence of compensation? It would have to be renal compensation. The kidneys would be doing a couple of things. 

• • 1. They would be trying to conserve H+ ions and 

    2. Eliminate bicarbonate

Where would we see evidence of either of these things?

• • 1.  ABG values would show lower levels of HCO3- if the kidneys had been able to eliminate enough HCO3- to begin to raise the pH back toward normal.

    2. The conservation of H+ and elimination of HCO3- would results in less acidic (more alkaline) urine.

Do we see evidence of either of these things?

At this point we do not. So this respiratory alkalosis is uncompensated.

What if we have slightly different numbers from the ABG and add in a urinalysis as well:

• • • • pH = 7.5 (normal is...?)

      • pCO2 = 30 mm Hg (normal is 38-44)

      • pO2 = 85 mm Hg (normal is 75-100)

      • [HCO3-] = 19 meq/liter (normal is 22-26)

      • Urine analysis:

        • • urine pH = 7

Just as we did before, we look at the pH first. Since the pH is high, we know it is an alkalosis. Next we look at the pCO2 and HCO3-. Now, both are abnormal, so which one causes a high pH, and which could be evidence of compensation? 

Well, low CO2 means less carbonic acid, which would cause a higher pH; a low HCO3-, however, would lead to a low pH. Since the pH is high, we can surmise that it was a respiratory problem that caused the pH imbalance, and that the low HCO3- is the renal compensation. Further evidence for that comes from the urinalysis, which shows an alkaline urine, indicating the body is excreting bicarbonate. Here, then, we have a partially compensated respiratory alkalosis.

What about a situation where renal or respiratory compensation brings the ratio of bicarbonate:carbonic acid back to 20:1, thus reestablishing a pH in the normal range?

Here is another, similar, set of ABG values:

• • • • pH = 7.44 (normal is...?)

      • pCO2 = 30 mm Hg (normal is 38-44)

      • pO2 = 54 mm Hg (normal is 75-100)

      • [HCO3-] = 17 meq/liter (normal is 22-26)

If we follow the instructions for determining this pH imbalance, we first look at the pH and see that it is in the normal range. That leaves us with two options. Either we have no pH imbalance, or we have a fully compensated pH imbalance. 

When we look at the pCO2 and HCO3- levels, we see that they are both in the abnormal range, which indicates that there is an acid-base disturbance. 

We know that low CO2  can cause a respiratory alkalosis, and low HCO3- would lead to a metabolic acidosis. To determine which one is fully compensated for in this patient we can look at two things. 

First, where is the pH within the normal range? It is on the high side, making it more likely that this was an alkalosis that has been compensated for. Secondly, we see that something is wrong with oxygenation. Remember the potential causes of a respiratory alkalosis? 

What would happen if a person had very low levels of oxygen in their blood (and thus reaching their tissues)? 

The body would respond by increasing respiration rate. By doing so, more CO2  is lost, which could result in a respiratory alkalosis. So, in this case, based on those pieces of evidence, this patient has a respiratory alkalosis that has been fully compensated.

If the pH is in the normal range, why do we care? 

Well, compensation is not correction. There is some underlying problem that needs to be addressed, and those CO2  and HCO3- levels need to be brought back to normal, perhaps with medical intervention.

The link below is to a web page titled "Interpretation of ABGs: Acid - Base Balance A Four Step Method" that will reinforce what was just explained above. It will walk you through the same process of analysis that Fig. 3-14 in your book does, and there are also links on the left of the site that take you to more information about pH as well as a link to apply the 4-step method to sample case studies.

Simple method for Acid Base Balance Interpretation

Lastly, as a way to review pH imbalances and practice analyzing ABG data to predict the type of pH imbalance a patient has, there is a graded assignment in Canvas.