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Transport of Carbon Dioxide
Forms of Carbon Dioxide
Carbon dioxide is carried in the blood in three forms: dissolved,
attached to hemoglobin, and converted to bicarbonate ions. Dissolved
CO2 accounts for 7–10 percent of the carbon dioxide carried in the
blood. This is also the only form of carbon dioxide that diffuses from the
tissues into the blood and from the blood into the alveoli for expulsion
from the body. Here, we will examine in depth the transfer of carbon
dioxide using hemoglobin or by the formation of bicarbonate.
Carbaminohemoglobin and Bicarbonate
Carbon dioxide can bind to any protein and form a carbamate
compound. The protein found in the highest concentration in red blood
cells is hemoglobin, and 20–23 percent of the CO2 carried in the blood is
bound to hemoglobin in the form of carbaminohemoglobin. In the
capillaries of the systemic tissues, CO2molecules attach to the terminal
amino acids of the alpha and beta chains of the hemoglobin molecule.
Deoxygenated hemoglobin (hemoglobin with no or less than the
maximal oxygen bound, abbreviated HHb), such as that found in
metabolically active tissues, binds CO2 easily. In the capillaries of the
lungs, the elevated levels of oxygen found in alveoli force the carbon
dioxide off the hemoglobin molecule and oxidize the protein, freeing up
hydrogen ions. Although some carbon dioxide is transported as
carbaminohemoglobin, the majority, about 70 percent, is dissolved in
the blood as bicarbonate ions that arise from the reversible reactions
discussed below.
Carbon dioxide in the presence of water can be reversibly converted to
carbonic acid. Carbonic acid is not very stable and readily dissociates
into a hydrogen ion and a bicarbonate ion. In fact, this is why
carbonated beverages are acidic. Carbon dioxide is added to the drink
mixture under pressure and dissolves in the beverage. When the CO2 has
bubbled out of the beverage, it tastes flat because the acid is gone. The
same thing happens in red blood cells, except that red blood cells
contain an enzyme called carbonic anhydrase (CA), which is capable
of facilitating one million reactions per second per enzyme molecule.
Because of the enzyme, most of the CO2 dissolved in the blood is quickly
converted to carbonic acid, which breaks down to form, hydrogen ions,
and bicarbonate ions.
The chemical reaction for this process is the following:
CO2- (in the presence of CA) + H2O ⇆ H2CO3 ⇆ H++ HCO3
Where H2O is water, CA is carbonic anhydrase, H2CO3 is carbonic acid,
H+ is a hydrogen ion, and HCO3- is a bicarbonate ion. The second part
of the reaction, which produces the hydrogen and bicarbonate ions, does
not have an enzyme, but depends on the dissociation of the weak acid.
This series of reactions provides buffering for the blood.
Carbon dioxide production occurs in many tissues, especially muscle.
The carbon dioxide produced diffuses from the tissue of origin into a
systemic capillary and dissolves in the plasma. A small amount of the
carbon dioxide is transported this way. Most of the CO2 that diffused
into the plasma diffuses into a red blood cell and reacts with
intracellular water molecules to produce hydrogen and bicarbonate ions.
Remembering that the reactions are reversible, it makes sense that
levels of accumulated products will drive the direction of the reaction
sequences. The dissociation of carbonic acid is driven by the relative
concentration of carbonic acid compared to the relative levels of
bicarbonate(carbonic acid’s conjugate base). A build-up of bicarbonate
in the RBCs would slow or halt the dissociation of carbonic acid. This
build-up doesn’t usually happen because, RBCs have a membrane
channel that allows bicarbonate to leave the RBC and enter the blood
plasma. To maintain electric neutrality inside the RBC and in the
plasma, every time a negative bicarbonate ion leaves the red blood cell it
is exchanged for a negative chloride ion from the plasma. This exchange
is called the chloride shift. The bicarbonate ion in the plasma becomes
part of the blood’s buffering system, maintaining blood pH within a
narrow range. Deviation from this range compromises organ function
and can cause death. The hydrogen ion liberated from the conversion of
CO2 to bicarbonate binds to a a deoxygenated hemoglobin molecule
causing it to become reduced. Deoxygenated hemoglobin easily picks up
a molecule of CO2, creating carbaminohemoglobin. Hemoglobin is an
important buffering agent for the hydrogen ions produced from the
conversion of carbon dioxide to bicarbonate ions. If this buffering did
not occur, the intracellular fluid of the red blood cell would become
progressively more acidic, resulting in deterioration of cell functions.
Some CO2 from the tissues can be found as as bicarbonate ions and
dissolved CO2 in the plasma. The remainder of the carbon dioxide is
attached to hemoglobin or it is still in the carbonic acid form and will
stay in the red blood cells.
When the blood enters the pulmonary capillaries, gaseous carbon
dioxide in the plasma diffuses into the alveoli. Some of the bicarbonate
diffuses from the plasma into the red blood cells, and a chloride ion
passes back into the plasma, reversing the chloride shift that occurred in
the capillaries in the systemic tissues. The high partial pressure of
oxygen in the alveoli causes the carbaminohemoglobin to dissociate into
deoxyhemoglobin, a hydrogen ion, and a molecule of carbon dioxide.
The released CO2 is available for diffusion. The free hydrogen ion
combines with a bicarbonate ion and reforms carbonic acid. The
carbonic acid is converted back to carbon dioxide and water under the
influence of carbonic anhydrase.