Pulmonary Physiology

Acid-Base Balance: From the Lung’s Perspective

None of this should be terribly new to you – you’ve covered acid-base balance in previous courses
during the first year. Today, let’s just review acid-base balance from the perspective of the lung.

First, recall that the body functions best when the pH of the blood remains within a tightly regulated
range (approximately 7.38 – 7.42). This is because the body is made up of proteins, and protein
structure (and thus function) is greatly affected by pH. Once you forget about the scary chemistry
involved, you realize that how the body maintains its pH in this narrow range is actually quite
fascinating!

The HCO3- Buffer System

Remember the notion of “Buffers” from Chem 101? Buffers are substances that help solutions resist
large changes in pH in response to the addition of H+ (acid) or OH- (base) ions – basically, they suck them
up... Not surprisingly, the body has some buffers. The one we think of most often (and will discuss
today) is HCO3- , but other non-HCO3- buffers include hemoglobin, organic and inorganic phosphates,
and proteins.

The unique thing about the body’s HCO3- buffer system is that it is an open system. What I mean by that
is that there is an escape valve. Remember this central reaction:

CO2 + H20  H2CO3  HCO3- + H+

What happens when additional H+ is added to the system? The reaction is driven to the left and you get
increased formation of water (which we like) and CO2 (which we can breathe out!!!!). That’s the escape
valve! The more acid you add to the system (the body), the more CO2 the body generates. If we
couldn’t get rid of it, the pH of the blood would go down dramatically and we would become acidemic.
Luckily, the lungs come to the rescue and remove the CO2 from the body, thus making the body’s HCO3-
buffer system an open system that is HIGHLY effective at maintaining the blood pH in that narrow
acceptable range. (For all you budding nephrologists out there, yes, the kidney is also an escape valve
for the system – it controls the elimination of HCO3- just like the lung controls the elimination of
CO2….it’s just not nearly as efficient as the super-lung!)

At this point, I just want to remind you of a few points you learned when we covered diffusion and
transport (if these are not immediately apparent to you, please go back to those lecture notes to
review!):
  Most of the CO2 generated by the body’s tissues is carried in the blood as HCO3-, not as
dissolved CO2 gas (that’s the PCO2, right?).
 Due to the extremely high solubility of CO2, the PACO2 (alveolar) = PaCO2 (arterial), ALWAYS.
 The PACO2 and, therefore also the PaCO2, are determined by alveolar ventilation (respiratory
rate x [tidal volume – dead space]).

As you learned in period 1 (and will review during the pulmonary block), the brain controls breathing
(alveolar ventilation) in response to blood pH. Chemoreceptors on the ventrolateral medulla respond to
changes in the pH of the CSF (which mirrors changes in the blood) by increasing or decreasing the
respiratory rate and/or tidal volume. Increasing either of those in response to a drop in the pH of the
blood will increase alveolar ventilation and therefore will eliminate more CO2, bringing the pH back up
towards the desired range.

The Four Basic Disturbances

Basically, there are four ways that the acid-base balance of the body may be disrupted. For now, let’s
think of each of those in isolation and as an immediate (uncompensated) process. Refer to the reaction
below as you think about each of them:

CO2 + H20  H2CO3  HCO3- + H+

The other thing that I want you to keep in mind is the following equation (science geeks, this comes
from the Henderson-Hesselbach equation for the HCO3- buffer system):

H+ = 24 x PaCO2 / [HCO3-]

I do not mean for you to memorize this equation! Here’s what I want you to just understand from
looking at it: The blood pH (which is based on the H+ concentration) is determined by the ratio of
dissolved CO2 (the PaCO2) to the HCO3- concentration. It’s all about the relative concentrations of those
two factors. More CO2 than HCO3- and you’re acidemic. More HCO3- than CO2 and you’re alkalemic.
That’s it. Ok, so here are your disorders.

1) Respiratory Acidosis: If normal ventilation is impaired, the lungs are not able to clear CO2 and the
blood becomes acidemic. That’s because as CO2 builds up, the ratio of CO2 to HCO3- increases. Can you
think of some potential etiologies of respiratory acidosis?

2) Respiratory Alkalosis: On the other hand, if ventilation is increased beyond the normal range, too
much CO2 is cleared from the body and the blood will become alkalemic. That’s because the ratio of CO2
to HCO3- decreases. Can you think of some potential etiologies of respiratory alkalosis?

3) Metabolic Alkalosis: If H+ ions are lost from the body (often caused by severe vomiting), HCO3- will
build up and the ratio of CO2 to HCO3- will again decrease. The blood will become alkalemic.
4) Metabolic Acidosis: The loss of HCO3- from the blood (often caused by severe diarrhea) will cause the
blood to become acidemic because the ratio of CO2 to HCO3- will increase. Similarly, if exogenous acids
are ingested (toxins like salicylates, methanol, ethylene glycol, etc.) or if endogenous acids (substances
like urate, lactate, ketoacids, etc.) are made in excess or not efficiently eliminated, the blood will
become acidemic. That’s because additional H+ ions have been directly added to the system. Those H+
ions will combine with HCO3- ions and drive the reaction above to the left – with the formation of
additional CO2 and the loss of HCO3-. So ultimately, adding acids to the body will cause the ratio of CO2
to HCO3- to increase and will lead (not surprisingly) to acidemia.

A more complete discussion of the metabolic disorders (anion gap vs. non-ion gap, etc.) is outside the
scope of this lecture, but I do want to point something out that I think will help you to conceptualize this
whole acid-base process. It’s pretty basic and you probably have already noticed it, but always
remember that an acid-base disturbance caused by the lungs (respiratory acidosis or alkalosis) is due to
an issue with CO2 handling. On the other hand, an acid-base disturbance caused by a metabolic process
(metabolic acidosis or alkalosis) is due to an issue with HCO3- handling. As you’ll soon see,
compensation works just the same – the lung can adjust CO2 handling and the kidney can adjust HCO3-
handling.

Compensation

Ok, so we started off by saying that the body does not tolerate significant fluctuations in the blood pH.
So how does it maintain the blood pH is such a tightly regulated fashion? Here is where those escape
valves come in – compensation. Ultimately, the kidney can compensate for respiratory problems by
altering the amount of HCO3- it eliminates and the lung can compensate for metabolic problems by
altering the amount of CO2 it eliminates.

For each of the disturbances that we described above, there is a discreet mechanism for compensation.
Again, remember our favorite reaction:

CO2 + H20  H2CO3  H+ + HCO3-

1) Metabolic Compensation for Respiratory Acidosis: If the lungs are not eliminating enough CO2, the
blood becomes acidemic or alkalemic? Acidemic. As CO2 rises relative to HCO3- and the blood pH goes
down, the kidney will snap into action and alter the amount of
HCO3- being eliminated. Should the kidney save more HCO3-
or eliminate more HCO3-? The problem is acidemia, so the
kidney will SAVE HCO3- to bring the pH back up towards the
normal range. An important point here: note that based on
the reaction above, even before the kidney got involved, the
amount of HCO3- in the blood was already increasing (as CO2
increases, the reaction is driven to the right with formation of
more H+ and more HCO3-). Metabolic compensation caused a
yet further increase in the HCO3-. So look at the scary picture on the right. Start at the point labeled
“normal point.” Now follow the blue line that represents hypoventilation (i.e. retention of CO2, the
cause of the respiratory acidosis). Notice that the blue line leads towards a lower pH and higher HCO3-
(even before any compensation begins!). From here, follow the green line that represents renal
compensation. What happens to the HCO3- ? To the pH? Yes, the kidney saves yet more HCO3- and this
brings the pH back down towards normal. The red line marked “actual path” represents what happens
in reality (when compensation is happening
gradually along with the primary process).

2) Metabolic Compensation for Respiratory

Alkalosis: If the lungs are eliminating too much
CO2, the blood becomes acidemic or alkalemic?
Alkalemic. As CO2 decreases relative to HCO3-,
the blood pH rises and again the kidney will snap
into action. This time, since the problem is
alkalemia, the kidney will eliminate more HCO3-
to bring the blood pH back down towards
normal. Again, note that based on the reaction
above, the amount of HCO3- in the blood was
already decreasing even before the kidney got
involved. Metabolic compensation caused a yet further decrease in the HCO3-. So now let’s look at the
second scary picture. Again, start at the point labeled “normal point.” Now follow the blue line that
represents hyperventilation (i.e., loss of CO2, the cause of the respiratory acidosis). Notice that the blue
line leads towards a higher pH and a lower HCO3- (even before any compensation begins!). From here,
follow the green line that represents renal compensation. What happens to the HCO3-? To the pH?
Yes, the kidney excretes even more HCO3- and this brings the pH back down towards normal. This one
doesn’t have a red line marked “actual path” like the last graph because the onset of respiratory
alkalosis is almost always way too fast for the kidney to keep up with.

3) Respiratory Compensation for Metabolic Alkalosis: If the body loses H+ (like from severe vomiting),
the blood becomes acidemic or alkalemic? Alkalemic. As the amount of H+ decreases, the HCO3-
increases relative to the CO2 and the pH rises. Now it’s the
lung that needs to help out. In this case, should the lungs
save or eliminate more CO2? The problem is alkalemia, so
the lungs will save CO2 to bring the pH back down towards
normal. So now let’s look at the third scary picture. Again,
start at the point labeled “normal point.” Now follow the
blue line that represents maybe vomiting (i.e., loss of H+,
the cause of the metabolic alkalosis). From here, follow the
green line that represents respiratory compensation. What
happens to the CO2? To the pH? Yes, the lung saves more
CO2 and this brings the pH back down towards normal.
Again, the red line indicates what would happen in reality when the respiratory compensation was
occurring along with the primary process.

4) Respiratory Compensation for Metabolic Acidosis: If the body loses HCO3- (or gains H+), the blood
becomes acidemic or alkalemic? Acidemic. As the amount of H+ increases, the HCO3- decreases relative
to CO2 and the blood pH drops. Again, the lungs will need
to help out. In this case, the lungs will respond by
increasing alveolar ventilation to eliminate more CO2 and
bring the pH back up towards normal. So now let’s look at
the last scary picture. Again, start at the point labeled
“normal point.” Now follow the blue line that represents
the onset of metabolic acidosis (ingestion of an exogenous
acid or increased production/decreased elimination of an
endogenous acid). Notice that the blue line leads towards a
lower pH. From here, follow the green line that represents
respiratory compensation. What happens to the CO2? To
the pH? Yes, the lung eliminates more CO2 and this brings the pH back up towards normal. Again, the
red line indicates what would happen in reality when the respiratory compensation was occurring along
with the primary process.

Time Course of Compensation

Of note, the lungs can compensate much more quickly for metabolic problems than the kidney can for
respiratory problems. This is because A) face it, the lung is just the best organ, and B) because renal
compensation requires the production of proteins for pumps etc. that exchange H+ and HCO3- ions in
the tubules, while CO2 moves very quickly via diffusion in the lungs. Last year when you learned about
compensation you saw a table like this one:

Acid-Base Disturbance Primary Compensation Predicted Compensatory Response

Disturbance
Metabolic ↓ [HCO3- ] ↓ PCO2 Expected PCO2=( 1.5 * HCO3) + 8
Acidosis Or 1 mEq/L ↓ in HCO3- → 1.3 mm Hg ↓ in PCO2

Metabolic Alkalosis ↑ [HCO3- ] ↑ PCO2 Expected PCO2=( 0.7 * HCO3) +20

Or 1 mEq/L ↑ in HCO3- → 0.7 mm Hg ↑ in PCO2

Respiratory Acidosis
Acute ↑ PCO2 ↑ [HCO3- ] Expected HCO3= 24 + [(PCO2 -40)/10]
Or 1 mm Hg ↑ in PCO2 → 0.1 mEq/L ↑ in HCO3-
Chronic ↑ PCO2 ↑ [HCO3- ] Expected HCO3= 24 +{4* [(PCO2 -40)/10]}
Or 1 mm Hg ↑ in PCO2 → 0.4 mEq/L ↑ in HCO3-
Respiratory Alkalosis
Acute ↓ PCO2 ↓ [HCO3- ] Expected HCO3= 24- {2* [(40- PCO2 )/10]}
Or 1 mm Hg ↓ in PCO2 → 0.2 mEq/L ↓ in HCO3-
Chronic ↓ PCO2 ↓ [HCO3- ] Expected HCO3= 24 – {4* [(40-PCO2)/10]}
Or 1 mm Hg ↓ in PCO2 → 0.4 mEq/L ↓ in HCO3-
Again, I don’t expect you to memorize these equations (you’ll get more into this during the renal block
and will need to know these equations during the third year), but I do want you to note that while renal
compensation for the respiratory processes has two phases – the acute and chronic phases, respiratory
compensation for metabolic processes has only one phase. This has to do with the fact that the lung can
make changes in the body’s CO2 levels much more quickly than the kidney can make changes in the
body’s HCO3- levels.

One other thing I want you to take note of – it’s a nice little trick: Notice that compensation always
follows the same direction as the primary process. In other words, if the primary issue is that the CO2 is
too high, the compensation will be for the HCO3- to increase as well. If the primary problem is that the
HCO3- is too low, the compensation will be for the CO2 to decrease as well. Similarly, if the problem is
that CO2 is too high, the compensation will be for the HCO3- to increase as well. If the problem is that
the CO2 is too low, the compensation will be for the HCO3- to decrease as well. The arrows in the first
two columns of the table always go in the same direction… Can you explain why that is? Take a
moment to think about it. Really. I don’t believe you tried.

Ok, maybe you did. The reason is because as we stated earlier, the pH is determined by the ratio of CO2
to HCO3-. The closer the ratio is to 1, the more “normal” the pH is. So, if the numerator increases or
decreases, the denominator needs to move in the same direction (same thing for changes in the
denominator) to keep the ratio near 1!

Approach to the Acid-Base Dilemma

Ok, so not that you have the background, you probably want to know how to put it into action. To do
that, let’s examine some patients! First, remember your normal values:

pH: 7.38 – 7.42

pCO2: 38 – 42 mmHg
HCO3- : 22 – 28 mEq/L

Next, consider a stepwise approach:

1) Is the patient acidemic or alkalemic?

 If the pH is low, acidemia is present, if it’s high, alkalemia is present.
 Remember that the body cannot (and will not) overcompensate. So you can believe the pH, it
will tell you the primary disorder.

2) Is the pCO2 high or low?

 If the problem is acidemia, a high CO2 tells you that the primary issue is a respiratory acidosis, a
low CO2 would tell you that there is respiratory compensation for a primary metabolic acidosis.
 If the problem is alkalemia, a low CO2 tells you that the primary issue is a respiratory alkalosis, a
high CO2 would tell you that there is respiratory compensation for a primary metabolic alkalosis.
Mr. Herbert Goldberg

Mr. Goldberg is a 76 year old man with a 60 pack-year smoking history. He presents to the ER with
several days of worsening shortness of breath and productive cough. The patient is afebrile, the HR is
104, BP is 140/80, and RR is 22. Auscultation of the chest reveals diffuse wheezing. His O2 saturation is
89% on room air, so you send an ABG to evaluate his pO2 and here is what you get:

pH 7.33 / pCO2 65 / pO2 58 / HCO3- 34

First of all, good job on predicting the hypoxemia – you put him on 5L NC and the saturation increases to
97%. But what else did the ABG tell you?

1) Is the patient acidemic or alkalemic?

 The pH is low, so acidemia is present.

2) Is the pCO2 high or low?

 The pCO2 is high, so this must be the reason for the acidosis – it is a primary respiratory acidosis!

3) Bonus points – what’s up with the HCO3- ?

 The HCO3- is high because the kidney is saving HCO3- (metabolic compensation) in order to bring
the pH back up towards normal. This has been going on for a few days, so the kidney has had
enough time to “catch up.” If this hadn’t occurred, the pH would be MUCH less than 7.33. Yay
kidney!

4) Bonus points – what’s the underlying clinical problem?

 Mr. Goldberg has COPD, which is characterized by an obstructive ventilatory defect with small
airways collapse and impaired CO2 clearance. This will make more sense after you’ve learned
more about COPD – if it doesn’t, please find me and we’ll talk.

Miss Tara Huffington

Tara is a 12 year old girl with severe asthma. She is brought to the ER by her mother because of two
hours of worsening shortness of breath triggered by walking through the perfume department of a big
department store. Tara is afebrile, the HR is 115, BP is 110/70, and RR is 36. Auscultation of the chest
reveals diffuse wheezing. An ABG is sent and you find:

pH 7.55 / pCO2 30 / pO2 89 / HCO3- 24

1) Is the patient acidemic or alkalemic?

 The pH is high, so alkalemia is present.

2) Is the pCO2 high or low?

 The pCO2 is low, so this must be the reason for the alkalosis – it is a primary respiratory
alkalosis!
3) Bonus points – what’s up with the HCO3- ?
 The HCO3- is normal because the kidney has not yet had time to get into gear and start
eliminating HCO3- (metabolic compensation) in order to bring the pH back down towards
normal. If this went on for a few days, the HCO3- would go down and the pH would be much
closer to the normal range.

4) Bonus points – what’s the underlying clinical problem?

 This is a pretty classic example of an acute asthma exacerbation. Asthma is also characterized
by an obstructive ventilatory defect with small airways collapse, but patients very rarely
demonstrate an impairment of CO2 clearance unless it is very, very severe. Mostly this is
because they ramp up their respiratory rate so much. In fact, if you see a patient presenting
with a severe exacerbation of asthma who does not have a respiratory alkalosis, you better be
thinking about intubation because that patient is simply too tired to breath fast enough to blow
down his CO2 and is on his way to a very bad outcome.

Ms. Maria Hernandez

Ms. Hernandez is an 86 year old woman who is brought by EMS to the ER from Green Glades nursing
home for fever and decreased mental status. She was treated yesterday for a urinary tract infection. In
the ER her temperature is 101.4, HR is 106, BP is 80/50, and the RR is 26. Physical exam reveals dry
mucus membranes and decreased skin turgor. An ABG is sent and you find:

pH 7.30 / pCO2 25 / pO2 80 / HCO3- 12

1) Is the patient acidemic or alkalemic?

 The pH is low, so acidemia is present.

2) Is the pCO2 high or low?

 The pCO2 is low, so this cannot be the reason for the acidemia – it must be a primary metabolic
acidosis!

3) Bonus points – what’s up with the HCO3- ?

 The HCO3- is low because that is the mechanism of the primary disorder – this is a metabolic
acidosis. There is too much acid and not enough HCO3-. Here the pCO2 is low because the lung
is compensating – it is blowing off CO2 to bring the pH back up towards normal.

4) Bonus points – what’s the underlying clinical problem?

 This is a pretty classic example of sepsis, likely due to a urinary tract infection. Sepsis is one of
the most common causes of metabolic acidosis in hospitalized patients. Sepsis causes the
formation of large amounts of lactic acid in the body (the lack of perfusion causes widespread
conversion to anaerobic metabolism and the production of lactate).
Mr. Eli Johnson

Mr. Johnson is a 63 year old man with pancreatic cancer admitted three days ago for bowel obstruction.
He has not been able to eat or drink due to the presence of a nasogastric tube that has been kept on
continuous wall suction. An ABG was performed on room air this morning by the intern when he
complained of mild SOB. You (the senior resident) review the ABG with the intern:

pH 7.55 / pCO2 50 / pO2 99 / HCO3- 42

Pre-1) Are you concerned (the senior resident) about his oxygenation? No, it looks pretty good! A pO2
of 99 mmHg on room air is just fine. Perhaps a better first step by your intern would have been to check
the O2 saturation before getting an ABG. But good thing he got it, because:

1) Is the patient acidemic or alkalemic?

 The pH is high, so alkalemia is present.

2) Is the pCO2 high or low?

 The pCO2 is high, so this cannot be the reason for the alkalemia – it must be a primary metabolic
alkalosis!

3) Bonus points – what’s up with the HCO3- ?

 The HCO3- is high because that is the mechanism of the primary disorder – this is a metabolic
alkalosis. There is too much HCO3- relative to CO2. Here the pCO2 is high because the lung is
compensating – it is saving CO2 to bring the pH back down towards normal.

4) Bonus points – what’s the underlying clinical problem?

 Just like severe vomiting, an NG tube to continuous suction can cause a metabolic alkalosis due
to volume depletion and the loss of HCl acid from the stomach.

Critical Points

1) The body’s main buffer is HCO3-. The HCO3- buffer system is HIGHLY effective at maintaining the
blood pH in a narrow range because it is an open system – the lungs can regulate the elimination or
retention of CO2 and the kidneys can regulate the elimination or retention of HCO3-.

2) Ultimately, it’s the ratio of CO2 to HCO3- in the blood that determines blood pH:
- Too much CO2 relative to HCO3- and you get acidemia
- Too much HCO3- relative to CO2 and you get alkalemia

3) There are four main acid-base disturbances:

- Respiratory acidosis: Not enough CO2 being cleared by the lungs
- Respiratory alkalosis: Too much CO2 being cleared by the lungs
- Metabolic acidosis: Not enough HCO3- available
- Metabolic alkalosis: Too much HCO3- available
4) Primary respiratory disorders are caused by problems with CO2 handling – metabolic compensation
will be through adjustments in HCO3- handling by the kidneys.

5) Primary metabolic disorders are caused by problems of HCO3- handling – respiratory compensation
will be through adjustments in CO2 handling by the lungs.

6) While renal compensation for the respiratory processes has two phases – the acute and chronic
phases, respiratory compensation for metabolic processes has only one phase. This has to do with
the fact that the lung can make changes in the body’s CO2 levels much more quickly than the kidney
can make changes in the body’s HCO3- levels.

7) Compensation always follows the same direction as the primary process. In other words, if the
primary issue is that the CO2 is too high, the compensation will be for the HCO3- to increase as well.
If the primary problem is that the HCO3- is too low, the compensation will be for the CO2 to decrease
as well.

8) Normal values:
pH: 7.38 – 7.42
pCO2: 38 – 42 mmHg
HCO3- : 22 – 28 mEq/L

9) Stepwise approach to the ABG:

1) Is the patient acidemic or alkalemic?
o If the pH is low, acidemia is present, if it’s high, alkalemia is present.
o You can’t over compensate, so the pH will tell you the primary disorder.
2) Is the pCO2 high or low?
o If the problem is acidemia, a high CO2 tells you that the primary issue is a respiratory
acidosis, a low CO2 would tell you that there is respiratory compensation for a primary
metabolic acidosis.
o If the problem is alkalemia, a low CO2 tells you that the primary issue is a respiratory
alkalosis, a high CO2 would tell you that there is respiratory compensation for a primary
metabolic alkalosis.