Transport of Oxygen and Carbon Dioxide in Body Fluids Chapter 24

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

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

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

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.

Myoglobin is the respiratory pigment in muscles

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

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

% 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-23-04-0.jpg Figure 24.4a

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

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

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 90-100 mm Hg (0.95*760*0.14) = loading pressure (Pl) in the lungs anphys2e-fig-23-04-0.jpg

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-23-05-0.jpg

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

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.

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-23-06-0.jpg

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

P50: oxygen partial pressure at which the pigment is 50% saturated How to measure P50 (Fig. 24.9 ) P50: oxygen partial pressure at which the pigment is 50% saturated P50 marks the point at which Hb = HbO2 At rest, P50 = 25-30 mm Hg, for humans anphys-fig-22-09-0.jpg

Bohr effect or shift The Bohr effect is a physiological phenomenon first described in 1904 by the Danish physiologist Christian Bohr (1855-1911), Who is his son?

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

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

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

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

O2 concentration of blood (mL O2/100 mL) Figure 24.12 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

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.

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

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

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-23-14-0.jpg

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-23-15-0.jpg

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

Percent saturation (%) Figure 24.16 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

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

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

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

Days after transfer to low-O2 water Figure 24.20 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

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

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-

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-23-20-0.jpg

Haldane Effect Deoxygenated blood can carry more CO2 than oxygenated blood (Haldane effect) Left shift Fig. 24.22

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).

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).

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

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.

Figure 24.23 The major processes of CO2 uptake by the blood in a systemic blood capillary of a vertebrate AnPhys3e-Fig-24-23-0.jpg

A day in the life of hemoglobin