Hamburger Phenomenon (Chloride Shift) - Short Note
Definition: The Hamburger phenomenon, better known as the chloride shift, is the exchange of chloride ions (Cl⁻) and bicarbonate ions (HCO3⁻) across the red blood cell (RBC) membrane that happens as blood picks up and releases CO2. It is named after Hartog Jacob Hamburger, who first described it.
Why it happens (easy explanation)
- CO2 produced by tissues diffuses into the RBC.
- Inside the RBC, the enzyme carbonic anhydrase rapidly converts CO2 + H2O into carbonic acid (H2CO3).
- H2CO3 immediately splits into H+ and HCO3-.
- The H+ is buffered by binding to deoxyhemoglobin (this also drives the Haldane effect).
- HCO3- builds up much faster inside the RBC than in the plasma, so about 70% of it moves out of the cell into the plasma through a membrane transporter called anion exchanger 1 (AE1 / Band 3).
- Since the cell cannot lose a negative charge without gaining one back (electroneutrality), Cl- moves into the RBC from the plasma to replace the HCO3- that left. This inward Cl- movement is the "chloride shift."
In the lungs, the reverse happens: CO2 leaves the RBC to be exhaled, HCO3- moves back into the cell, and Cl- moves back out into plasma - so the cells shrink slightly.
Simple diagram (tissue capillary side)
TISSUE CAPILLARY (CO2 loading)
Plasma RBC (inside)
------ ------------
CO2 ----------> CO2 + H2O
| (carbonic anhydrase)
v
H2CO3
|
H+ <--+--> HCO3-
| |
binds Hb (Hb.H+) | (~70% leaves cell)
v
<------------------- HCO3- (out to plasma)
Cl- -------------> Cl- (in, via AE1/Band3)
(to balance charge lost by HCO3- leaving)
- Book Title: Ganong's Review of Medical Physiology, 26th Edition, p. 644
Key points to remember
- Mediator protein: AE1 (Band 3), present in high amounts on the RBC membrane.
- About 70% of the HCO3- formed in RBCs enters plasma; Cl- moves in to replace it.
- Process is fast - essentially complete within 1 second.
- Because an extra osmotically active particle (Cl- or HCO3-) enters the cell for every CO2 that comes in, RBCs swell slightly in venous blood and shrink again in the lungs. This is why venous hematocrit is about 3% higher than arterial hematocrit.
- Works together with the Haldane effect (deoxygenated Hb carries more CO2 and H+) to make CO2 transport efficient.
Figure reference (original textbook diagram):
Figure 35-4, Ganong's Review of Medical Physiology: CO2 enters the RBC, is hydrated to H2CO3 by carbonic anhydrase, splits into H+ (binds deoxyhemoglobin) and HCO3- (exits via AE1/Band 3 in exchange for Cl-).