The Big Equation

At the beginning of A&P II I usually write the following on the board:

CO₂ + H₂O <-> H₂CO₃ <-> H⁺ + HCO₃^-

While I am writing, I narrate it this way:

"When carbon dioxide dissolves in water, especially in the presence of the enzyme carbonic anhydrase, they combine to form carbonic acid, which readily falls apart into a hydrogen ion and a bicarbonate ion."

This ends up being a stock part of my A&P2 lectures because it comes up in discussion of so many systems this semester.  So I thought I would dedicate a post to the reaction - and its implications for the systems that we study this semester.

The first time we discuss this reaction is often the first day of A&P II.  Discussing the chapter on Blood, we say that red blood cells (RBCs) contain an enzyme called carbonic anhydrase.  The textbook shows the equation in a paragraph of the text, and we say that this enzyme in the RBCs helps form H⁺ and HCO₃^- from CO₂ and H₂O.  This is the first mention of the enzyme and the reaction.

We discuss the reaction a second time in the Respiratory system chapter.  A number of concepts are introduced in the Blood/Cardiovascular chapters that are expanded/built upon in the Respiratory chapter, and this is one of them.  In this chapter we learn that carbon dioxide is carried in the bloodstream mostly as bicarbonate ion (HCO₃^-).  So how does it get converted to bicarbonate (and back)?  By using our reaction!  The carbonic anhydrase enzyme that is in the RBC (which we learned on Day 1...) converts the carbon dioxide to bicarbonate ion and back again.

The gas laws tell us that gases move down their partial pressure gradients.  This is, in fact, the driving force for "our equation" too.  When CO₂ is high, it drives the equation to the right, converting the CO₂ to bicarbonate.  When the partial pressure of CO₂ falls, it drives the reaction to the left and converts bicarbonate back to carbon dioxide to be breathed out.

So we started by learning RBCs have an enzyme called carbonic anhydrase that catalyzes "our equation".  Then we learned that bicarbonate is how the majority of CO₂ is carried in the bloodstream, and it is formed by that enzyme and that equation.  So that's it, right?

Nope.  Eventually we discuss the digestive system.  Parietal cells lining gastric pits also express the enzyme carbonic anhydrase.  So what happens in those cells?  You guessed it .... "when carbon dioxide dissolves in water ... " In the stomach, the point isn't to make bicarbonate, the point is to make the acid.  The hydrogen ion moves down its concentration gradient into the lumen of the stomach where it forms HCl - hydrochloric acid.  So stomach acid forms from the same mechanism, "our equation".

Then once the stomach contents reach the duodenum, the pH needs to be neutralized.  The pancreas secretes bicarbonate to neutralize the stomach acid.  Don't be surprised when I tell you that pancreatic acinar cells express the enzyme carbonic anhydrase which help them produce the bicarbonate that is secreted.

So if you didn't learn it initially, and you didn't learn it with the respiratory or digestive systems, you might think you could get away with not memorizing or understanding the equation.  Then ....

In the renal system chapter, we review a number of figures that appear to be a complicated mess of transporters.  In one set of figures, though, we see something familiar.  We see the carbonic anhydrase enzyme.  We see .... our equation.  And suddenly, it is something familiar in a complicated process.

Renal tubule cells also express carbonic anhydrase.  They also do "the equation".  The bicarbonate ion is important for blood pH homeostasis, so it is reabsorbed into the bloodstream.  The acid is pretty much a waste product and can be excreted in the urine.

By this point is it usually April or November.  Did you ever think you would understand a chemical equation so well?  But wait, there is another chapter to go...and we end up coming full circle.

Because this last chapter is about acid-base balance in the blood.  About respiratory acidosis and alkalosis, caused when the respiratory system doesn't expel CO₂ correctly. About metabolic acidosis and alkalosis, which are compensated for by changes in breathing.  We have come back to the beginning of A&P II, to the Blood and Respiratory chapters.  But we have also come back to the beginning of A&P I, to pH and acids and bases and buffers.

"Our reaction" is reversible.  High P_CO2 drives the reaction to the right, low P_CO2 drives the reaction to the left.  These are facts that we memorized in August or January.  Now we can use them to understand the body's reaction to acid-base imbalance, one of the most complicated topics of the semester.

This post is getting a little long, so I think I will save the details of acid-base balance for another time.  Suffice it to say that we can "blow off" CO2 to lower the partial pressure to restore pH imbalances.

"Our equation" is an efficient little reaction.  It uses one enzyme to convert a waste product into bicarbonate and hydrogen ion.  But it is more than that.  It is how the blood carries carbon dioxide through the bloodstream.  It is how stomach acid gets made, and then neutralized.  It is how kidney tubules retain bicarbonate and dump acid.  It is how we maintain blood pH homeostasis.  One equation, but a multitude of homeostatic and regulatory functions in the human body.

So readers, do you find it fascinating?  What question do you have about The Big Equation?