Gas Transport

Question 1

How Gases Are Carried in the Body

Answer 1

Less than 5% of O2 and CO2 carried in the blood is in physical solution, 95% of the carrying capacity for these gases depends upon reversible chemical reactions with oxygen being bound in the lung and released in the tissues and carbon dioxide doing the converse.

Question 2

Henry’s Law and O₂

Answer 2

• Oxygen obeys Henry’s law and at a PO2 of 100 mm Hg, 3 ml of O2 is dissolved in one liter of blood; i.e. .003 ml/100 ml of blood/mmHg; i.e. 3 ml/Liter of blood at a PO2of100.
• Thus, at a resting cardiac output of 6 liters per minute, only 3 x 6 = 18 mls of oxygen could be delivered if we relied upon dissolved gas.
• Instead, roughly 195 mls per liter can be carried due to hemoglobin = 195 x 6 or 1170 mls of oxygen bound to hemoglobin can be delivered to the body per minute.
• Remember that PaO2 determines both how much oxygen will be dissolved and how much will be bound by hemoglobin. The partial pressure of oxygen in a glass of water will be greater than that in the artery, however, the content will be much lower because the water lacks hemoglobin.

Question 3

Hemoglobin

Answer 3

• Hemoglobin consists of heme (Iron in the ferrous state in the center of a porphyrin ring) and globin arranged as four protein chains each with a heme group.
• Adult hemoglobin has two alpha and two beta chains. Alterations in the globin chain (over 100 such described) can alter the ability to bind oxygen.
• Furthermore, normal hemoglobin A alters its ability to bind oxygen due to alterations in the spatial relationship of the heme and globin molecules.
• Each molecule of Hb can hold four oxygen molecules (1 per heme). Oxygenation of one accelerates oxygenation of the remaining heme groups and similarly release of oxygen by one heme group accelerates release by the others.

Question 4

Carrying Capacity of Hemoglobin

Answer 4

One gram of Hb can combine with 1.34 ml of oxygen when 100%saturated.

Question 5

What will be the potential OXYGEN CAPACITY when blood has a hemoglobin concentration of 15 gm/dl i.e. 15 grams of Hb per 100 ml of blood?

Answer 5

1.34 ml O2 / gm Hb x 15 gm Hb/100 ml blood = 20.1 vol% (ml O2 / 100 ml blood)

•Conversely, in sickle cell anemia the hemoglobin might be 7.5 gm/ 100 ml blood and as a result there would be only 10 vol% oxygen content. The body compensates for this by increasing cardiac output to deliver adequate oxygen to the tissues.

Question 6

Oxygen Saturation

Answer 6

The actual amount of oxygen carried divided by the oxygen capacity. The % saturation depends upon thePO2.

Question 7

Hemoglobin in the Lungs/Tissue

Answer 7

In the lung the Hb is nearly 100% saturated, but at the range seen in the tissue (i.e. PO2 = 40-50) the Hb rapidly desaturates, giving up oxygen to the tissue.

Question 8

P₅₀

Answer 8

The P50 is the partial pressure of oxygen at which the hemoglobin is 50% saturated. This is usually about 28 mmHg.

Question 9

Reserve O₂

Answer 9

The Hb is 90% saturated at a PaO2 of 60. Thus, there is a significant reserve between the usual PaO2 of 100 and the 90% saturation point at a PaO2 of 60. Also, raising the PO2 above 100 mmHg will increase the oxygen content of the blood very little.

Question 10

Difference in P_aO₂ and P_vO₂

Answer 10

• The sudden decrease in saturation between a PaO2 of 60 and the usual mixed venous PvO2 of 40 means that much oxygen can be given off without a large drop in partial pressure. This maintains the driving pressure to get oxygen out to the tissues where the PO2 of the mitochondria might be only 1-3 mmHg.
• If the curve was a linear decrease in saturation from a PaO2 of 100 to 0 mmHg, then there would be a significant loss in PaO2 to give up oxygen and this would reduce the driving pressure for diffusion into the tissues.

Question 11

Factors Altering the Combination of Oxygen and Hemoglobin

Answer 11

1. Oxygen affinity of hemoglobin can be described by the partial pressure (mmHg) at which the hemoglobin is 50% saturated, the P50. As noted above, this is normally a PaO2 of 28mmHg.
2. If the HbO2 curve shifts to the left, i.e. decreasing the P50, then for any given PO2 the blood will be more saturated.
3. If the HbO2 curve shifts to the right then the P50 increases and for any given PO2, the blood will be less saturated

Question 12

Right Shifting of the HbO₂ Curve

Answer 12

Right ‘shifting’ of the HbO2 curve aids in oxygen delivery to the tissues by reducing the hemoglobin’s affinity for oxygen.

Question 13

Left Shifting of the HbO₂ Curve

Answer 13

Left ‘shifting’ of the HbO2 curve aids in oxygen uptake in the lung by increasing the hemoglobin’s affinity foroxygen.

Question 14

How does CO reduce O₂ Delivery?

Answer 14

• First, carbon monoxide vigorously binds to the hemoglobin making it unavailable to carry oxygen. In effect, it causes an ‘anemia’; i.e. less hemoglobin is available carry oxygen.
• Second, when hemoglobin binds carbon monoxide, it decreases the P50; i.e. it increases the hemoglobin’s affinity for oxygen.
• Thus, hemoglobin not only holds less oxygen, it also doesn’t give it up well in the tissues. It is not due to a reduction in the PaO2; the PaO2 will be normal. (Remember the glass of water with a higher PaO2 than arterial blood, but a lower content.)

Question 15

Fetal Hemoglobin

Answer 15

• Fetal hemoglobin has a higher affinity for oxygen than does adult hemoglobin. This shifts the HbO2 curve to the left and decreases the P50 of Hb F as compared to adult Hb A.
• This is important as the PaO2 in-utero is about 28 mmHg. The infant needs to have a P50 that is lower than the mother’s to efficiently take oxygen from the maternal placental circulation.

Question 16

Adequate Delivery of O₂ to the Tissues Requires…

Answer 16

• Oxygen content in the blood: Adequate PaO2 and hemoglobin
• Cardiac output: Adequate delivery to arteries of the oxygen content
• Vascular supply: Adequate delivery to tissues of arterial blood

Question 17

Types of Tissue Hypoxia

Answer 17

1. Hypoexemic Hypoxia
2. Anemic Hypoxia
3. Circulatory Hypoxia
4. Histotoxic Hypoxia

Question 18

Hypoexemic Hypoxia

Answer 18

Arterial oxygen tension is low (low PaO2) leading to a low oxygen saturation of hemoglobin. (lung disease)

Question 19

Anemic Hypoxia

Answer 19

PaO2 is normal, but oxygen carrying capacity is low leading to low O2 content. (anemia)

Question 20

Circulatory Hypoxia

Answer 20

Oxygen content is normal, but blood flow to the tissues is reduced. (shock)

Question 21

Histotoxic Hypoxia

Answer 21

Oxygen content and blood flow through the tissue is normal, but the tissue cannot use the oxygen at a cellular level. (cyanide poisoning)

Question 22

3 Ways CO₂ is Carried in the Body

Answer 22

1. Physical Solution
2. HCO₃-
3. Carbamino Compounds (COO- bound to NH₄+ on hemoglobin)

Question 23

How many times more soluble is CO₂ than O₂?

Answer 23

• 20 times
• At normal body temperature, 0.06 ml of CO2 is dissolved per 100 ml of blood per mmHg of partial pressure.

-The PaCO2 is 40 and thus 2.4 mls of CO2 are dissolved per 100 ml of blood –or- 24 ml per liter of blood. This is eight times more than dissolved oxygen.

Question 24

HCO₃-

Answer 24

CO2 also combines with H2O in the plasma to form H2CO3, a small portion of the H2CO3 then dissociates into H+ and HCO3-.

• In the erythrocyte, this reaction is catalyzed by the enzyme carbonic anhydrase leading to much larger amounts of HCO3- in the erythrocyte.
• This is the major form in which CO2 is carried in the blood.
• Hemoglobin can also accept H+ thus encouraging the dissociation of H2CO3 into H+ and HCO3-. Hb is a better hydrogen ion acceptor than HbO2.

Question 25

Carbamino Compounds

Answer 25

CO2 can also join with amine groups on amino acids in proteins to form carbamino compounds. Once again, hemoglobin, is the major protein performing this action because of its high number of amino acids with amine groups, and once again, Hb forms carbamino compounds better than HbO2.

Question 26

Answer 26

• Thus, most of the CO2 is carried as bicarbonate and less than 1/10thof this amount is carried as carbamino compounds.
• However, as there is a relatively large reduction in carbamino compounds, these latter compounds account for 30% of the total change. This is due to hemoglobin changing its affinity for carbamino compounds when it is oxygenated.

Question 27

CO₂ Dissociation Curve vs O₂ Dissociation Curve

Answer 27

The CO2 dissociation curve differs from the O2 dissociation curve in three ways:

• Higher total content of CO2 in the blood per mmHg of partial pressure.
• Steeper slope, i.e. more change in CO2 content per change inPCO2.
• No effective plateau or maximum content.

Question 28

Haldane Effect

Answer 28

• As the PO2 goes up the CO2 dissociation curve shifts downward, i.e. less CO2 is carried in the blood.
• Thus, as the blood is oxygenated in the lung, the blood gives up CO2 aiding in clearance into the alveoli and out of the body.
• In the tissues, as blood gives up oxygen, the capacity for CO2 increases aiding in uptake of CO2 from the tissues and transport to the lung.
• The Haldane effect occurs because when hemoglobin is oxygenated it releases hydrogen ions into the red cell which then join with bicarbonate to form carbonic acid. This then dissociates into water and carbon dioxide which is released. Also, the carbon dioxide from carbamino compounds is given off during oxygenation of the hemoglobin.

Question 29

CO₂ Exchange in the Lung

Answer 29

The alveolar CO2 (PACO2) is lower than the pulmonary capillary partial pressure causing CO2 to diffuse into the alveolus, lowering blood CO2 content.

Question 30

CO₂ Exchange in the Tissue

Answer 30

The tissue CO2 partial pressure is higher than the capillary partial pressure causing CO2 to diffuse into the capillary, raising blood CO2 content.

Question 31

CO₂ and the Law of Mass Action

Answer 31

•The law of mass action determines the net movement of CO2 either to or from carbamino compounds, and HCO3-

CarbaminoCompounds:

CO2 + Hb•NH2 ↔ Hb•NH•COOH ↔ Hb•NH•COO + H+

Bicarbonate (Hydration of CO2):

CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+

C.A. enzyme in red blood cell

Question 32

Law of Mass Action in Lung

Answer 32

The drop in PCO2 causes carbamino compounds and bicarbonate to generate CO2. Most of this occurs in the red blood cell (RBC) due to Hb-carbamino -> CO2 and HCO3- -> CO2 with the aid of RBC carbonicanhydrase.

Question 33

Law of Mass Action in Tissue

Answer 33

The converse from what happens in the lungs occurs in the tissues with the formation of carbamino compounds and HCO3- (again predominately in the RBC).

Question 34

Erythrocytes and Carbonic Anhydrase

Answer 34

The erythrocytes contain carbonic anhydrase (plasma does not), and thus RBCs break down or form HCO3- faster than the plasma.

Question 35

Erythrocytes and Carbonic Anhydrase: Lung

Answer 35

HCO3- in RBCs decreases rapidly and HCO3- diffuses into the RBC from the plasma. H+ can’t follow, so chloride ion (CL-) thus exits the cell (chloride shift) to maintain electric balance.

Question 36

Erythrocytes and Carbonic Anhydrase: Tissue

Answer 36

HCO3- is formed rapidly in the RBC and diffuses out of the RBC into the plasma. H+ can’t follow so chloride ion (CL-) enters the cell (chloride shift) to maintain electrical balance.

Question 37

Oxygenation of Hemoglobin and CO₂

Answer 37

• Oxygenation of the hemoglobin releases H+ ions causing the conversion of HCO3- to CO2 and H2O.
• Oxygenation of hemoglobin also favors the breakdown of carbamino compounds. This effect (HALDANE) accounts for almost 50% of CO2 transfer.

Question 38

Blood Flow and CO₂

Answer 38

Blood flow through the tissue is critical to CO2 clearance and the rapidity with which changes in CO2 excretion can respond to changes in metabolic production depend upon both ventilatory and cardiovascular responses to CO2.