Gas Transport

Question 1

What are the main ways to transport oxygen in the blood ?

Answer 1

1. Dissolved in plasma

2. Attached to haemoglobin

Question 2

Which of the two ways to transport oxygen is more efficient ? How so ?

Answer 2

Attached to haemoglobin much more efficient. Because:

1) Dissolved in plasma
Dissolution proportion to partial pressure, but oxygen is poorly soluble. Therefore arterial blood with a PO2 of 100 mmHg contains approximately only 0.3ml O2/100ml
Cardiac output at rest is 5 litres/min, so this would deliver 3ml O2/litre x 5 = 15ml O2/ min. Tissue requirements at rest are around 250ml O2/min, hence there would be a huge deficit.

2) Attached to haemoglobin
- Positive co-operative binding – once first O2 is bound (easily reversible combination – HbO2), the next three are easier to bind – (ie the affinity of Hb for O2 alters, and increases with extent of Hb saturation)

Question 3

Describe the basic structure of haemoglobin.

Answer 3

Haem – iron containing compound

Globin – protein of 4 polypeptide chains

Question 4

How many bindings sites for oxygen are there on Hb ?

Answer 4

4 binding sites

Question 5

Draw and describe the Oxygen-haemoglobin dissociation curve.

Answer 5

Refer to slide 5 of lecture on “Gas Transport”

Sigmoidal shaped curve
1) In the lungs the PO2 is high (after gas exchange has taken place from 40 mmHg
rising up to 100 mmHg), so Hb essentially fully saturated in the lungs
2) At the tissues the PO2 has fallen by more than half, but the Hb is still around 75% saturated from 98-99% (thanks to flat upper plateau, which means that even if PO2 falls, saturation is not greatly altered,
so at altitude O2 supply is still usually adequate)
3) Steep lower part of graph means tissues can extract lots of O2 for small drop of PO2 (25% is normally unloaded at tissues, leaving large reserve without needing to increase respiratory rate or cardiac output., allowing e.g. holding your breath)

Question 6

Identify other factors (besides PO2) which influence haemoglobin saturation, stating how each factors affects haemoglobin saturation, and whether they increase or decrease Hb saturation.

Answer 6

♪ ↑ temperature, H+, CO2 and 2,3-bisphosphoglycerate (2,3-BPG), all shift the curve to the right. All modify the 3-D structure of haemoglobin, decreasing its affinity for oxygen, hence shift to right (e.g. warmed up muscles are better at releasing O2, hence good reason for pre-race prep). Increased CO2 leads to an increase in H+ which weakens the Hb-O2 interaction (i.e. the Bohr effect).
♪ At the lungs, the curve shifts to the left and haemoglobin’s affinity for oxygen is increased (due to decreased CO2).

Question 7

Define the Bohr effect.

Answer 7

Decreased affinity of hemoglobin for oxygen caused by an increase of carbon dioxide; the oxyhemoglobin dissociation curve is displaced to the right because of higher partial pressure of carbon dioxide and lower pH.

Question 8

Graph the effect of decreased CO2 (or H+), and increased CO2 (or H+), on the Hb-O2 dissociation curve.

Answer 8

Refer to slide 7 in lecture on “Transport of Gas”.

Question 9

How can we calculate total amount of oxygen carried in blood ?

Answer 9

• Amount carried by haemoglobin + amount dissolved
• Amount carried by Hb is determined by Hb concentration in the blood, multiplied by the maximum oxygen carrying capacity of Hb multiplied by % saturation of Hb

• Hence,
Total = ([Hb] * capacity * % saturation) + amount dissolved

Question 10

Identify the normal values for each of the variables in the formula for total oxygen in blood. Then, calculate normal amount of oxygen carried in blood for 100 mL of normal arterial blood.

Answer 10

⌂ [Hb] is 15 g Hb/100 ml blood
⌂ Capacity is 1.35 ml O2/g Hb (lies between 1.35 and 1.39 normally)
⌂ PO2 is 100 mmHg
⌂ % saturation is 98%
⌂ The amount dissolved is 0.3 ml O2/100ml

Total =
(15 * 1.35 * 98%) + 0.3= 20 ml O2/100 ml blood, or 200 ml O2/litre

Question 11

What is the total amount of oxygen normally in blood ?

Answer 11

20 ml O2/100 ml blood, or 200 ml O2/litre

Question 12

Identify the main ways to transport CO2 in blood, stating the proportion of CO2 carried each way.

Answer 12

1. Dissolved in plasma (7-10%)
2. Bound to haemoglobin (10-20%)
3. As bicarbonate (70-80%)

Question 13

Why does dissolved CO2 in plasma account for more transport of CO2 than dissolved O2 in plasma accounts for transport of O2 ?

Answer 13

Greater solubility than oxygen, so this mechanism has more significant effect in respiration overall.

Question 14

Describe the main feature of CO2 binding to Hb.

Answer 14

☼ Carbaminohaemoglobin
☼ Binds to the amino acids, not the haem so does not directly compete with oxygen
☼ Loading and unloading is directly related to PCO2 and degree of oxygenation of Hb.
☼ CO2 binding obeys to Haldane effect

Question 15

Define the Haldane effect.

Answer 15

Deoxygenation of Hb increases its ability to bind CO2, (eg in the tissues) and vice versa in the lungs, oxygenation of Hb releases CO2 into plasma for transport into alveoli.

Question 16

Explain the process of CO2 transport as bicarbonate, both in the lungs and tissues.

Answer 16

• When CO2 dissolves in water it produces carbonic acid, which is unstable so
rapidly breaks down to H+ and HCO3- (=bicarbonate)
CO2 +H2O↔H2CO3 (carbonic acid) ↔H+ +HCO3-

• The first stage of the reaction is slow in plasma, but the presence of carbonic anhydrase in RBC makes it very rapid.
• Formed bicarbonate diffuses down concentration gradient into plasma
• H+ binds to Hb (Bohr shift from earlier), but H+ is buffered in plasma, so acidity of tissue does not alter greatly
• Chloride shift – chloride ions move into RBC to maintain electrical balance (to compensate for diffusion of bicarbonate out of RBC)
• Process reversed in the lungs, HCO3- moves back into RBC (chloride moves out), reacts with H+ to form carbonic acid which is rapidly reacted by carbonic anhydrase to form CO2 and water. CO2 diffuses into alveoli space.

Question 17

Summarise the main events in oxygen release and carbon dioxide pickup at the tissues.

Answer 17

• CO2 produced, and coming out of tissues. Some dissolves in plasma (small proportion), the majority enters the RBC. A small portion of this interacts directly with Hb to form Carbaminohaemoglobin. The majority of the CO2 entering the RBC is rapidly converted into carbonic acid (using carbonic anhydrase), which is unstable and dissociated into bicarbonate + H+. This bicarbonate later moves through its gradient and diffuses out of cell. To compensate, extra chloride shift (moving in RBC).
• Oxygen comes off Hb and diffuses into tissues (some oxygen also dissolved in plasma, diffuses into tissues)

Question 18

Summarise the main events in CO2 release and oxygen pickup in the lungs.

Answer 18

• Bicarbonate diffuses back into RBC and Chloride ions come back out into the plasma. Bicarbonate interacts with H+, forming carbonic acid, which is rapidly changed into CO2 and water using carbonic anhydrase. CO2 then diffuses out of the RBC across the alveoli membrane wall into alveoli, and is breathed out. The CO2 dissolved in the plasma also diffuses out of the RBC across alveoli membrane wall into alveoli. Carbaminohaemoglobin dissociates into Hb and CO2 (in RBC) and CO2 diffuses out of RBC across alveoli membrane wall into alveoli.
• Oxygen diffuses (using concentration gradient) across into the RBC and binds onto Hb (some O2 also dissolves in plasma).

Question 19

Explain the influence of CO2 on blood pH.

Answer 19

♦ The transport of CO2 is the main way to alter blood pH: alteration of alveolar ventilation (ie altering CO2 elimination) can change acid-base status of blood (through effect on bicarbonate).

♦ pH of blood can be calculated from Henderson-Hasselbach equation:
pH = pK + (log [bicarbonate] / [CO2] )

where,
-pk is the negative logarithm (base 10) of the acid dissociation constant of carbonic acid. It is equal to 6.1.
-the bicarbonate concentration is measured (around 24 mM)
-the CO2 concentration is calculated
according to the solubility of the gas and the partial pressure of CO2 (i.e. 0.03 x 40 = 1.2)

Question 20

Calculat the pH of blood using the Henderson-Hasselbach equation for the bicarbonate buffer system (in blood). How can we change the pH of the system ?

Answer 20

pH = 6.1 + log [24 mM] [0.03 * 40 mmHg]
pH = 6.1 + log 20 pH = 7.4

Changing either the bicarbonate levels or the CO2 levels will alter the pH.

Question 21

Draw a Davenport diagram, explaining its different features.

Answer 21

Refer to slide 17 in lecture on “Gas Transport”.

♠ pH < 7.35 acidosis
pH>7.45 alkalosis

♠ line AB shows plasma pH change as CO2 changes.
If ventilation decreases, CO2 increases (blowing off less CO2), pH falls (i.e. more H+) and HCO3- increases. This is respiratory acidosis.
If the patient hyperventilates, blowing off more CO2, pH rises (i.e. less H+) and the levels of HCO3- falls. This is respiratory alkalosis

♠ line CD shows plasma pH change when non-volatile acid (e.g. HCl, lactic acid) is added/removed (for a static PCO2 level of 40 mmHg). This is metabolic acidosis and metabolic alkalosis .