1. Transport of Oxygen and Carbon Dioxide in Body Fluids
Chapter 24

2. Solubility of oxygen in aqueous fluids is low
Oxygen Transport
Solubility of oxygen in aqueous fluids is low
Metalloproteins (respiratory pigments)
contain metal ions
reversibly bind to oxygen
increase oxygen carrying capacity >50-fold
Plasma:
3 ml of O2 per liter
Blood:
200 ml of O2 per liter

3. Respiratory Pigments
Hemocyanins
Mollusks and some arthropods (horseshoe crabs)
Contain copper
Usually dissolved in the hemolymph
Appears blue when oxygenated
Hemerythrins
Brachiopods, some annelids
Contains iron directly bound to the protein
Usually found inside coelomic cells
Appears violet-pink when oxygenated
Hemoglobin

4. Hemoglobin Most common respiratory pigment
Figure 24.1
Hemoglobin
Most common respiratory pigment
Vertebrates, nematodes, some annelids, crustaceans, and insects
Globin protein bound to a heme molecule containing iron
Four globins / hemoglobin

5. Usually carried within Erythrocytes
3 Hemoglobin, cont.
Usually carried within Erythrocytes
Each red cell has about 270,000,000 hemoglobin molecules
Advantage for solutes, diffusion.
Reduced colloidal osmotic pressure
Chemical environment within cell can differ from blood plasma.

6. Myoglobin is the respiratory pigment in muscles

7. Fig.24. 2 Human developmental changes in hemoglobins
A non-reversible change in gene expression
Discussed later

8. Respiratory pigments bind O2 in a reversible chemical reaction
Hb + O2 <-> HbO2
HbO2 = oxyhemoglobin
Appears red when oxygenated
Hb4(O2)4

9. % O2 saturation of Hb as a function of PO2 in the plasma
A typical oxygen equilibrium curve for human arterial blood presented in two different ways
% O2 saturation of Hb as a function of PO2 in the plasma
anphys2e-fig jpg
Figure 24.4a

10. Oxygen Equilibrium Curves, cont.
Relationship between PO2 in the plasma and the amount of oxygen in a volume of blood (ml O2 per 100 ml of blood)
note dissolved O2
Figure 24.4b

11. Oxygen Equilibrium Curves, cont.
O2 content varies with hemoglobin content

12. Saturation tension for PO2 = 95% oxygen saturation.
Figure 24.4
As partial pressure increases, more pigment molecules bind oxygen, until the saturation point
Saturation tension for PO2 = 95% oxygen saturation.
For humans at rest, this is mm Hg (0.95*760*0.14)
= loading pressure (Pl) in the lungs
anphys2e-fig jpg

13. Shapes of Oxygen Equilibrium Curves
Upper part of curve is flat
Little effect for PO2 at loading site (lungs).
Hemoglobin is easily saturated.
O2 carrying capacity
anphys2e-fig jpg

14. Oxygen delivery by human blood, at the tissue level
at rest, Punloading is about 40 mm Hg
25% of O2 bound to Hb is delivered to the tissues.
about 5 ml O2/ 100 ml of blood, leaving 15 ml/100ml in venous reserve
Remember: Saturated blood carries 20 ml O2 / 100 ml

15. Oxygen delivery by human blood
during vigorous exercise
Tissue pO2 drops and enters steep part of curve.
Working muscle pO2 is about 20 mm Hg
10 more ml/100 ml of O2 are delivered to tissues that need it.

16. As the O2 partial pressure of blood falls, less and less of a drop in partial pressure is required to cause unloading of 5 vol % O2
anphys2e-fig jpg

17. oxygen equilibrium curves
Each molecule of myoglobin binds oxygen independently and therefore has a hyperbolic shape
Hemoglobin exhibits a sigmoidal curve because of cooperativity: hemoglobin has a higher affinity for oxygen when more of its heme groups are bound to oxygen

18. P50: oxygen partial pressure at which the pigment is 50% saturated
How to measure P50 (Fig )
P50: oxygen partial pressure at which the pigment is 50% saturated
P50 marks the point at which Hb = HbO2
At rest, P50 = mm Hg, for humans
anphys-fig jpg

19. Bohr effect or shift
The Bohr effect is a physiological phenomenon first described in 1904 by the Danish physiologist Christian Bohr ( ),
Who is his son?

20. A “shift to the right” changes the P50
P50 measures affinity of a pigment for O2
Curve shape reflects a trade off between loading and unloading O2
Low O2 affinity = gives up oxygen more readily, loads less easily = right-shifted curve (decreased P50)
High O2 affinity = gives up oxygen less readily = left-shifted curve
Fig 24.10

21. Figure 24.10 A “shift to the right”
A shift to the right means…
100
…the O2 partial pressure needed to saturate is higher, and…
Percent saturation (%) 50
…the P50 is higher. Thus…
P50
P50
…O2 affinity is lower.
Partial pressure of O2

22. Bohr effect or shift
A right shift in the normal curve due to decrease in pH and associated increase in PCO2.
Reduces oxygen affinity

23. The Bohr Effect
Right shift is largest in capillaries and facilitates offloading O2. to active tissues
A left shift occurs with increase in pH.
This facilitates oxygen binding at the respiratory surfaces

24. O2 concentration of blood (mL O2/100 mL)
Figure The Bohr effect typically enhances O2 delivery in an animal
The vertical arrows show the drop in blood O2 concentration as blood from the breathing organs flows through the systemic tissues. 15
A alone
(3.3 mL)
Shift between A and V
(7.2 mL)
V alone
(6.5 mL) 12 9
O2 concentration of blood (mL O2/100 mL) 6 A
Oxygen delivery to the tissues is greater in the presence of the Bohr shift (shift from curve A to curve V)… V 3
…than it would be if the blood were to adhere exclusively to curve A or curve V. 20 40 60
80 mm Hg
This is the assumed venous O2 partial pressure. 4
8 kPa
This is the assumed arterial O2 partial pressure.
Partial pressure of O2 in blood

25. Bohr Effect
As curve shifts right from A (lungs) to B (tissues), affinity for O2 decreases (compare the P50 values of the 2 curves)
More oxygen is released to the tissues
Left shift has minimal effect on oxygen uptake in the lungs.

26. Other Conditions That Affect Oxygen Affinity
Temperature
Increases in temperature decrease oxygen affinity; right shift
Promotes oxygen delivery during exercise

27. Other Conditions That Affect Oxygen Affinity
Temperature
Organic modulators of hemoglobin
2,3-DPG [bisphosphoglycerate]
2,3-DPG is synthesized in red blood cells
Usually one per hemoglobin molecule

28. Helps oxygen unloading at tissues (right shift)
The normal P50 of human hemoglobin within red blood cells depends on a normal intracellular concentration of 2,3-DPG
Increases in modulators such as 2,3-DPG reduces affinity of Hb for O2; right shift
Helps oxygen unloading at tissues (right shift)
anphys2e-fig jpg

29. DPG
DPG levels increase during exercise or at high altitudes when O2 demand is high
People with anemia often have a chronic increase in 2,3-DPG, (next slide).
Pregnant women increase intracellular DPG 30%.
anphys2e-fig jpg

30. Fetal hemoglobin (HbF) exhibits a low affinity for 2,3-BPG, resulting in a higher binding affinity for oxygen.
Fig. 24.2

31. Percent saturation (%)
Figure A decrease in the O2 affinity of hemoglobin can aid O2 delivery to the systemic tissues when the O2 partial pressure in the breathing organs remains high
100 90 80 70 60 50 40 30 20 10
A reduction in affinity enhances unloading of O2…
…more than it impairs loading. Consequently…
…each 100 mL of blood delivers more O2 from the breathing organs to the systemic tissues during each passage through the circulatory system when the affinity is reduced.
Normal
affinity
Reduced
affinity
Percent saturation (%)
Unloading
partial
pressure
Loading
partial
pressure 20 40 60 80
100 mm Hg 4 8
12 kPa
Partial pressure of O2 in blood

32. 4 ml O2 / 100 ml 8 ml O2 / 100 ml 12 ml O2 / 100 ml 16 ml O2 / 100 ml
Blood leaving the lungs carries 20 ml O2 / 100 ml. If there is no Bohr shift, and the oxygen pressure in the tissues is 40 mm Hg, how much oxygen is unloaded to the muscles?
4 ml O2 / 100 ml
8 ml O2 / 100 ml
12 ml O2 / 100 ml
16 ml O2 / 100 ml
20 ml O2 / 100 ml

33. 4 ml O2 / 100 ml 8 ml O2 / 100 ml 12 ml O2 / 100 ml 16 ml O2 / 100 ml
Blood leaving the lungs carries 20 ml O2 / 100 ml. With the Bohr shift, and the oxygen pressure in the tissues is 40 mm Hg, how much oxygen is unloaded to the muscles?
4 ml O2 / 100 ml
8 ml O2 / 100 ml
12 ml O2 / 100 ml
16 ml O2 / 100 ml
20 ml O2 / 100 ml

34. Box 24.2: Blood Cells and their Production
Erythropoietin (EPO) is secreted by the kidneys in response to low oxygen levels in the blood (e.g., altitude)
EPO stimulates RBC production in the bone marrow

35. Days after transfer to low-O2 water
Figure When water fleas are transferred to O2-poor water, their O2 transport system undergoes rapid acclimation because of altered gene expression
The O2 affinity of hemoglobin dramatically rises (P50 falls) because of synthesis of new molecular forms while simultaneously…
1.2
1.0
0.8
0.6
0.4
0.2
0.0
500
400
300
200
100
P50 (kPa)
Hemoglobin concentration (μM heme)
…the total concentration of hemoglobin in the blood sharply increases to a new plateau.
P50
Hemoglobin
concentration 2 4 6 8 10 12
Days after transfer to low-O2 water

36. Carbon Dioxide Transport
CO2 is more soluble in body fluids than O2
However, little CO2 is transported in the plasma
Some CO2 binds to proteins (carbaminohemoglobin)
Most CO2 is transported as bicarbonate

37. Carbon Dioxide Transport, cont.
Carbon dioxide (CO2) combines with water forming carbonic acid, which dissociates into a hydrogen ion (H+) and a bicarbonate ion:
CO2 + H2O ↔ H2CO3  HCO3- + H+
Carbonic anhydrase catalyzes the formation of HCO3-

38. Fig 24.21a Human carbon dioxide equilibrium curve
Relationship between PCO2 and total CO2 content of the blood
As CO2 partial pressure increases amount transported in the blood increases
Only a small amount is dissolved CO2.
Most is transported as bicarbonate.
anphys2e-fig jpg

39. Haldane Effect
Deoxygenated blood can carry more CO2 than oxygenated blood (Haldane effect)
Left shift
Fig

40. Carbon dioxide transport in blood
As bloods delivers O2 it picks up CO2
drops off about 50 ml/L of CO2 (~10%) per trip to lungs
Little CO2 is dissolved in solution (5%)
A good thing, too: if all the CO2 we make were carried this way, the pH of the blood would drop from its normal 7.4 to an instantly-fatal 4.5!
CO2 has only a small effect on pH (7.45 to 7.42) due to buffering by carbonates and proteins (especially hemoglobin).

41. Carbon Dioxide Transport
95% of the CO2 generated in the tissues enters the red blood cells:
About 20% of this is directly bound to hemoglobin (at a site different from the one that binds oxygen).
The rest (75%) is converted by the enzyme carbonic anhydrase into
bicarbonate ions that diffuse back out into the plasma and
hydrogen ions (H+) bind to the protein portion of the hemoglobin (thus having no effect on pH).

42. Vertebrate Red Blood Cells and CO2 Transport
Carbonic anhydrase is located within RBCs
Reactions to synthesize HCO3- occur in the RBCs even though most of this HCO3- is carried in the plasma
Cl- replaces the HCO3-
Figure 24.23

43. Carbonic anhydrase and velocity of CO2-water interaction
Carbonic anhydrase is highly specific for the reversible hydration reaction of CO2
getting CO2 out of water is not instantaneous
left to itself, not much would get to lung tissue
carbonic anhydrase speeds up one of the steps
H2CO3  H2O + CO2.

44. Figure The major processes of CO2 uptake by the blood in a systemic blood capillary of a vertebrate
AnPhys3e-Fig jpg

45. A day in the life of hemoglobin