Oxygen and Carbon Dioxide transport in the blood

Majority of O2 and CO2 is transported in the blood by: O2 combing with hemoglobin CO2 transformed into bicarbonate (HCO3¯)

Hemoglobin and O2 transport ±99% of O2 transported in blood is chemically bound to hemoglobin Hemoglobin is a protein found in red blood cells (erythrocytes) Each hemoglobin molecule can hold up to 4 O2 molecules

O2 combined with hemoglobin = oxyhemoglobin O2 that is NOT combined with hemoglobin = deoxyhemoglobin

Oxyhemoglobin Above is one of natures most complicated and unique creations, a protein molecule called hemoglobin. Each hemoglobin molecule is made up of 10,000 atoms, four of which are Iron atoms (blue spheres in the figure) that act as magnets to attract and hold the oxygen molecules. Each Iron atom rests on a Heme platform which serves to release the oxygen, out in the peripheral tissues. Each Red Blood Cell contains about 250 million molecules of hemoglobin, each cc of blood contains 5 billion Red Blood cells, you have approximately 5,000 cc's of blood in your vascular system. The reason we have so much hemoglobin is because oxygen does not easily dissolve in water (about 3% of all our oxygen is in the serum - the rest is bound to hemoglobin), so we have developed this unique system of oxygen transportation to meet our needs. When oxygen is bound to hemoglobin, it is called oxyhemoglobin.

The amount of O2 that can be transported depends on the concentration of hemoglobin Normal, healthy men = 150g/L of blood Normal, healthy women = 130g/L of blood When a hemoglobin molecule is completely saturated with O2  it can transport 1.34ml of O2

Therefore if hemoglobin if full (100% saturated with O2): Healthy male can transport 200ml of O2 Healthy female can transport 174ml of O2 100% saturation occurs at sea level (low altitude)

Partial Pressure The amount of O2 bound to hemoglobin is directly related to the partial pressure of O2. PO2: All gases exert pressure on the walls of their container because the molecules of gas bounce off the walls. Partial pressure is used to describe a mixture of gases. Defined as the pressure that any one gas would exert on the walls of the container if it were the only gas present

In the lungs, where the alveoli and capillaries exchange gases, PO2 is high Therefore O2 binds instantly to hemoglobin. As the blood circulates to other body tissue  the PO2 becomes lower Therefore hemoglobin releases O2 into the tissue because the hemoglobin cant maintain its full capacity of O2

Oxyhemoglobin Dissociation Curve In the alveolar capillaries in the lungs: O2 binding with hemoglobin is called loading Release of O2 from hemoglobin is called unloading Loading & unloading are reversible actions: Deoxyhemoglobin + O2 Oxyhemoglobin

Oxyhemoglobin Dissociation Curve An important tool for understanding how our blood carries and releases oxygen. Relates oxygen saturation (SO2) and partial pressure of oxygen in the blood (PO2) Determined by what is called "hemoglobin's affinity for oxygen“ how readily hemoglobin acquires and releases oxygen molecules from its surrounding tissue.

Oxygen hemoglobin dissociation curve

Oxygen Dissociation Curve Shows the percentage of O2 that is bound to hemoglobin at each O2 pressure. The curve is S-shaped with a steep slope between 10 and 60 mmHg and a flat portion between 70 and 100 mmHg. At rest the body’s O2 requirement is low & only ±25% is unloaded into muscles At intense exercise, PO2 can reach 20mmHg and 90% of O2 is unloaded into muscles

Significance of the Flat Portion The flat portion of the curve shows that the PO2 can fall from 100 to 60 mmHg and the hemoglobin will still be 90% saturated with O2 At pressures above 60mm Hg, the dissociation curve is relatively flat. This means the O2 content does not change much (even with large changes in the partial pressure of oxygen) E.g. PO2 can fluctuate between 90 – 100mmHg without a large drop in the percentage of hemoglobin that is saturated with O2 *This is important because there is a drop in PO2 with aging and with climbing high altitudes

Haemoglobin Saturation at High Values Lungs at sea level: PO2 of 100mmHg haemoglobin is 98% SATURATED Lungs at high elevations: PO2 of 80mmHg, haemoglobin 95 % saturated When the PO2 in the lungs declines below typical sea level values, haemoglobin still has a high affinity for O2 and remains almost fully saturated. Even though PO2 differs by 20 mmHg there is almost no difference in haemoglobin saturation.

Significance of Steep Portion PO2 reductions below 40 mm Hg produce a rapid decrease in the amount of O2 bound to hemoglobin. When the PO2 falls below 40 mm Hg, the quantity of O2 delivered to the tissue cells may be significantly reduced. As PO2decrease in this steep area of the curve, the O2 is unloaded to peripheral tissue as hemoglobin’s affinity for O2 diminishes. Therefore, small changes in PO2 will release large amounts of O2 from hemoglobin. * This is critical during exercise when O2 consumption is high.

Haemoglobin Saturation at Low Values

Factors that affect the O2 Dissociation pH - Change in the blood pH Temperature- temp increases = the curve moves to the right Carbon Dioxide – increased PCO2

Factors Altering Haemoglobin Saturation

Factors Altering Haemoglobin Saturation (Exercise)

Example During exercise, the oxyhemoglobin dissociation curve will shift to the RIGHT This is because the pH in the body is decreased (from increased lactic acid) AND Temperature increases during exercise

O2 Transport in muscle Myoglobin: - Protein that binds with O2 - Found in Skeletal and Cardiac muscle fibers (not in blood) - Acts as a shuttle to transport O2 from muscle cell membrane to the mitochondria - Found in large quantities in slow-twitch fibers (high aerobic capacity) - Smaller amounts in intermediate fibers - Limited quantity in fast twitch fibers

Myoglobin has a similar structure to hemoglobin, but is ¼ weight Difference in structure = difference in affinity for O2 Myoglobin has a greater affinity for O2: Therefore the myoglobin-O2 dissociation curve is much steeper = myoglobin releases O2 at very low PO2 values NB because PO2 in mitochondria of contracting skeletal muscle can be as low as 1mmHg.

Myoglobin stores O2 = reserve O2 for transition from rest to exercise At the start of exercise there is a lag time from the onset of muscular contraction and increased O2 delivery to the muscles Therefore O2 bound to myoglobin before exercise acts as a buffer so that muscles can receive O2 until the cardiopulmonary system can meet the new O2 demand

At the end of exercise: - myoglobin- O2 stores must be replenished to ensure O2 is available for the next time exercise begins Therefore O2 consumption above rest contributes to the O2 debt i.e. O2 consumption continues after exercise has stopped  leading to an O2 debt (O2 deficit) (Anaerobic metabolism of lactate – also called EPOC  Post Exercise Oxygen Consumption)

Carbon Dioxide Transport in Blood CO2 transported in the blood by: 1. Dissolved CO2 (±10%) 2. CO2 bound to hemoglobin (±20%) 3. Bicarbonate (HCO3¯)(±70%)

CO2 is converted to bicarbonate in red blood cells: A high PCO2 causes CO2 to combine with water, forming carbonic acid. This reaction is rapidly catalyzed by the enzyme Carbonic Anhydrase The carbonic acid then dissociates into bicarbonate ion and hydrogen ion. The hydrogen ion then binds with hemoglobin The bicarbonate ion diffuses out of the red blood cell into the blood plasma

Carbon Dioxide Transport Transport of CO2 Carbon Dioxide Transport CA CO2 + H2O H2 CO3 Carbonic Acid H2 CO3 H+ + H-CO3 Bicarbonate ion

Bicarbonate Ion Exchange Because bicarbonate carries a negative charge (anion), removal of a negatively charged molecule from a cell = electrochemical imbalance Therefore the negative charge must be replaced Bicarbonate is replaced by chloride (Cl¯) which diffuses from the plasma into the red blood cell This is called chloride shift  the shift of anions into red blood cells as blood moves through tissue capillaries

When blood reaches the pulmonary capillaries: PCO2 of the blood is greater than that of the alveolus = CO2 diffuses out of the blood across the blood-gas interface At the lungs: Binding of O2 to hemoglobin causes a release of the hydrogen ions (which are bound to hemoglobin) to promote the formation of carbonic acid H+ + HCO3¯ H2CO3

In conditions where PCO2 is low (at the alveolus), carbonic acid then dissociates into CO2 and H2O H2CO3 CO2 +H2O The release of CO2 from the blood into the alveoli is removed from the body in expired gas (CO2 we breathe out)

Revision Questions 1. What is the amount of hemoglobin found in a normal male and female? (2) 2. What is the amount of oxygen carried in a normal male and female? (2) 3. What is partial pressure? (2) 4. Explain the oxghemoglobin dissociation curve, focusing on the use, flat and steep portions (10) 5. What factors affect the oxghemoglobin dissociation curve? (3)

Revision Questions 6. How does exercise affect the oxghemoglobin dissociation curve? (3) 7. What is myoglobin and where is it found? (4) 8. How is myoglobin different to hemoglobin? (4) 9. What are the differences in myoglobin and oxygen at the start and end of exercise? Why does this happen? (8) 10. What are the way in which carbon dioxide is transported? (3) 11. How is carbon dioxide converted to bicarbonate? (5) 12. Explain bicarbonate exchange. (8)