Chloride Shift

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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.  

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Sample Problems:

True or False:

Carbonic anhydrase is the enzyme that catylyzes the ionization of H2CO3.

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Answers:

False, carbonic anhydrase catalyzes the formation of H2CO3.

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For more information on this topic, please refer to West , page 77.

Also, check out the following links that may be helpful:

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This page was written by Mary Alice Kalpakian, a student in this course.

BME 403 Pages maintained by the T.A., Douglas Miles.