Significance of chloride shift

The movement of chloride ions from the plasma into red blood cells as a result of the transfer of carbon dioxide from tissues to the plasma, a process that serves to maintain blood pH.

Bicarbonate and chloride ions are transported across the red blood cell membrane in opposite directions by the bicarbonate-chloride carrier protein.
The chloride shift is extremely rapid, occurring within 1 second.
The chloride shift results in the chloride content of venous blood being greater than that of arterial blood.

(The effect of carbon dioxide in the blood:
Haemoglobin can also bind carbon dioxide, but to a lesser extent. Carbaminohaemoglobin forms. Some carbon dioxide is carried in this form to the lungs from respiring tissues.

The presence of carbon dioxide helps the release of oxygen from haemoglobin, this is known as the Bohr effect. This can be seen by comparing the oxygen dissociation curves when there is less carbon dioxide present and when there is more carbon dioxide in the blood.



When carbon dioxide diffuses into the blood plasma and then into the red blood cells (erythrocytes) in the presence of the catalyst carbonic anhydrase most CO2 reacts with water in the erythrocytes and the following dynamic equilibrium is established

H2O + CO2 H2CO3

Carbonic acid, H2CO3, dissociates to form hydrogen ions and hydrogencarbonate ions. This is also a reversible reaction and undissociated carbonic acid, hydrogen ions and hydrogencarbonate ions exist in dynamic equilibrium with one another

H2CO3 H+ + HCO3-

Inside the erythrocytes negatively charged HCO3- ions diffuse from the cytoplasm to the plasma. This is balanced by diffusion of chloride ions, Cl-, in the opposite direction, maintaining the balance of negative and positive ions either side. This is called the 'chloride shift'.

The dissociation of carbonic acid increases the acidity of the blood (decreases its pH). Hydrogen ions, H+, then react with oxyhaemoglobin to release bound oxygen and reduce the acidity of the blood. This buffering action allows large quantities of carbonic acid to be carried in the blood without major changes in blood pH.

Hb.4O2 + H+ HHb+ + 4O2

(Hb.4O2 is sometimes written HbO8.)

It is this reversible reaction that accounts for the Bohr effect. Carbon dioxide is a waste product of respiration and its concentration is high in the respiring cell and so it is here that haemoglobin releases oxygen.


Now the haemoglobin is strongly attracted to carbon dioxide molecules. Carbon dioxide is removed to reduce its concentration in the cell and is transported to the lungs were its concentration is lower. This process is continuous since the oxygen concentration is always higher than the carbon dioxide concentration in the lungs. The opposite is true in respiring cells. )

Carbon dioxide produced in the tissue cells diffuses into the blood plasma. The largest fraction of carbon dioxide diffuses into the red blood cells. The carbon dioxide in the red blood cells is transported as: dissolved CO2, combined with hemoglobin, or as bicarbonate,(largest fraction).

The formation of bicarbonate ions, (HCO3- ) takes place by the following reactions:

Hydration of CO2: CO2 + HOH === H2CO3
Dissociation of H2CO3: H2CO3 === H+ + HCO3-

The H2CO3/HCO3- combination acts as the primary buffer of the blood. The hydration of carbon dioxide is a slow process but occurs rapidly in the red blood cells because a high concentration of the enzyme carbonic anhydrase catalyzes the reaction.

Bicarbonate diffuses out of the red blood cells into the plasma in venous blood and visa versa in arterial blood. Chloride ion always diffuses in an opposite direction of bicarbonate ion in order to maintain a charge balance. This is referred to as the "chloride shift".

The changes in concentration of CO2 or HCO3- ion can influence slight pH changes in the blood even though it is buffered. At the same time the concentration of H+ ions will influence the concentrations of CO2 and HCO3- ions.

The chloride shift describes the exchange of chloride anions for
bicarbonate anions across the erythrocyte's cell membrane. 

   To truly understand the purpose of the chloride shift, one must
first understand the transport system of carbon dioxide in the blood.
There are three primary ways that carbon dioxide is carried in the blood:
8% of carbon dioxide travels directly dissolved in plasma.  The reason
that this amount is so low is that carbon dioxide's solubility in blood
plasma is very low - about 2.5 Volume Percent. 
20% of carbon dioxide travels bound to proteins called carbamino
compounds.  The remaining 72% of carbon dioxide is transported as
biocarbonate ion in the blood stream.

   After carbon dioxide has diffused into erythrocytes, some of the
carbon dioxide binds to hemoglobin.  Scientists refer to this carbamino
compound as carbaminohemoglogin.  However, as noted in the above
percentages, most of the carbon dioxide does not react with the
hemoglobin.  Instead, the carbon dioxide reacts with a water molecule.
Carbonic anhydrase catalyzes the following reaction:

   Water+ Carbon dioxide ---->H2CO3.

H2CO3 then immediately divides into a proton and the bicarbonate anion.
The bicarbonate anion builds up inside the erythrocyte.  Because of this
high diffusion gradient of biocarbonate anion across the cell membrane,
the bicarbonate anion diffuses out of the cell into the blood plasma.
Since negative charge is moving out of the cell, chloride anions must move
into the cell from the surrounding blood plasma in order to allow
electrical balance to be achieved between the inside and outside of the
cell.

   I'm sure you're wondering why the H+ didn't just follow the
bicarbonate anion out of the cell so that charges would automatically be
balanced without having to bring in chloride anions.  The H+ cannot leave
the cell for two good reasons.  The first reason is that much of the H+
has alreaded binded to the hemoglobin molecule.  The second reason is the
H+ cannot easily diffuse across the cell membrane because the cell
membrane is practically impermeable to cations.  Also, think about the
following -  if the H+ was allowed to follow the bicarbonate out, it would
eventually begin to lower the blood pH and cause acidosis, a very
dangerous condition.

   Incidentally, while the bicarbonate ion is in the blood plasma, it
tries to neutraliz lactic acid that builds up in the blood because of
excessive exercise.  The presence of a very high bicarbonate ion
concentration in the plasma will cause resistance of the spontaneous
hydration of CO2.  This is logical because it resembles a negative
feedback model which prevents the excessive buildup of bicarbonate ion in
the blood plasma.