CO2 and O2 transport

Question 1

How is systemic partial pressure of oxygen measured and what is its normal value?

Answer 1

Measured using an arterial blood gas.

Arterial is normally 95-98mmHg (13.33 Kpa)

Venous is usually 40mmHg (around 5.3KPa)

Question 2

What two ways can oxygen be transported in the blood? Relative proportions?

Answer 2

2% dissolved in intra/extracellular fluids and 98% carried by haemoglobin

Question 3

What does Henry’s law state?

Answer 3

The amount of oxygen dissolved in the blood is proportional to the partial pressure.

Question 4

Why cant all oxygen be carried dissolved in plasma?

Answer 4

Solubility of oxygen in water is 0.23ml/litre/kPa, and at a partial pressure of oxygen at 14 in the arteries this gives 3ml/litre of dissolved oxygen.

Thus, for a cardiac output that ejects 5L of blood per minute, there is only 15ml/minute of oxygen in the solution. Therefore this is far insufficient of the resting metabolic oxygen consumption of 250ml/minute.

Question 5

Describe the structure of Hb?

Answer 5

Quaternary protein. It is a hetero-oligomer and consists of two different subunits: 2 alpha chains and 2 beta chains.

Question 6

What part of Hb facilitates oxygen binding, how many are there in one molecule?

Answer 6

Haem group which consists of a porphyrin ligand with a central Fe2+ ion.

This ion can reversibly bind oxygen by a coordinate covalent bond, facilitating oxygen saturation.

Each Hb has four O2 binding sites

Question 7

Why is Hb intracellular?

Answer 7

Packaged into RBs (rather than dissolved in plasma) prevent its filtration by glomerulus and to limit rises in blood viscosity.

Question 8

How is blood oxygen measured?

Answer 8

Amount of O2 bound to Hb sample expressed as a concentration of oxygen in the blood or as percentage saturation of maximal O2 capacity.

Question 9

Is the amount for PaO2 altered by lack of Hb?

Answer 9

No, total PaO2 depends on amount of O2 in solution in plasma e.g. PaO2 is normal in anaemia

Question 10

Is concentration of oxygen altered by lack of Hb?

Answer 10

Yes, it is reduced

Question 11

In lack of Hb will mixed venous PO2 be normal?

Answer 11

No, you end up extracting more oxygen if you are anaemic, so mixed venous O2 decreases.

Question 12

Does lack of Hb affect haematocrit?

Answer 12

No

Question 13

Does lack of Hb affect arterial pCO2?

Answer 13

It decreases it, because you are hypoxic, you hyperventilate

Question 14

What shape is the Hb dissociation curve for oxygen and why?

Answer 14

Sigmoidal

Due to cooperative binding of oxygen

Question 15

What does the sigmoidal shape mean for oxygen/Hb binding?

Answer 15

At areas of low pO2, the oxygen will dissociate as Hb affinity for oxygen is low

At areas of high pO2 the oxygen will load as Hb affinity for oxygen is high

Question 16

How does the dissociation curve shift?

Answer 16

Increases in CO2, [H+], and [2,3DPG] shift the Hb-O2 dissociation curve to the right, favouring oxygen unloading

This is a physiological benefit, as a more metabolically active muscle will have high demand for O2 and pH will be decreased, CO2 production increased and temperature will be raised.

Question 17

What effect does 2,3-DPG have on oxygen dissociation?

Answer 17

Produced during glycolysis

Reduces Hb affinity for O2 by binding to pocket in T state Hb.

Question 18

What is the Bohr effect and what is its physiological benefit?

Answer 18

The rightward shift of the dissociation curve in areas of high CO2 and H+, helps unload oxygen where it is needed.

Question 19

Why do raised concentrations of H+ and CO2 lead to lower Hb O2 affinity?

Answer 19

High [H+] and high [CO2] (through its conversion inside the red cell producing H+ OR through binding to Hb as carbaminohaemoglobin) stabilise deoxyhaemoglobin through facilitating formation of salt bridges.

Deoxygenated Hb is a weaker acid than Oxygenated Hb and therefore is a good buffer,

Deoxy-Hb binds to the excess H+ inside the erythrocyte and limits the decrease in pH caused by increased CO2 carriage.

This binding prevents Hb from binding to oxygen thus assisting the unloading at tissues with high pCO2.

CO2 reacts with free NH2 terminal groups on both the α and β chains of haemoglobin to form a new compound, carbaminohaemoglobin.

The combination of CO2 with NH2 groups is called a carbamate and drastically lowers the Hb affinity for oxygen.

Carbamate formation is reversible and occurs at high pCO2, thus, is a minor contributor to the Bohr effect.

Question 20

What are the different causes underlying inadequate o2 uptake of tissues (types of hypoxia)?

Answer 20

Hypoxic Hypoxaemia: low PAO2 (not ventilating lungs enough) and Sao2 (desaturated blood)

Stagnant/Ischaemic hypoxia: low perfusion (Q)

Anaemic hypoxia: low Hb (e.g. fewer RBC) or Low c (oxygen capacity of Hb)

Histotoxic hypoxia: High Pvo2 (partial pressure of venous blood) and Svo2 (saturation of venous blood) due to inability of tissues to use oxygen in the electron transport chain.

Question 21

Compare the total pressure of gases in arterial and venous blood

Answer 21

Total gas pressure greater in arterial blood

Question 22

Describe amount of oxygen lost to carbon dioxide made in systemic capillaries

Answer 22

Pressure-wise, far more oxygen lost from arterial blood than CO2 added to venous blood

Question 23

How can you increase PaO2?

Answer 23

Inhale pure oxygen

Question 24

What gives total oxygen content of blood?

Answer 24

Sum of oxygen dissolved in plasma and chemically bound to haemoglobin

Question 25

What is the normal value for systemic partial pressure (PCO2) of carbon dioxide?

Answer 25

Arterial is normally 40mmHg (5.33KPa)

Mixed venous blood pCO2 about 46mmHg

Question 26

How is CO2 transported in the blood? In what proportions?

Answer 26

As dissolved CO2 5-10%

In the form of bicarbonate (HCO3-) 85-90%

Complexed to terminal amine groups of blood proteins to carbamino CO2 5%

Question 27

Why does more CO2 travel in the plasma than oxygen?

Answer 27

It is around 20x more soluble than oxygen.

Question 28

Why doesn’t all CO2 travel in the plasma?

Answer 28

Only 156ml delivered to the lungs each minute, below 200ml (CO2 production)

Question 29

Where does CO2 bind to Hb?

Answer 29

The terminal amine groups, not the haem group

Question 30

Where does CO2 form bicarbonate?

Answer 30

Inside the red blood cells

Question 31

What happens to CO2 that moves into red blood cells at tissues?

Answer 31

Converted to carbonic acid by intracellular carbonic anhydrase, which subsequently dissociates into H+ and HCO3-

Question 32

Why is it beneficial for CO2 to be converted inside red blood cells at tissues?

Answer 32

Maintains the concentration gradient for CO2 to move out of tissues.

When pCO2 is high the equilibrium shifts to favour the conversion of CO2 to carbonate

Question 33

How do red blood cells remain electroneutrality and maintain equilibrium for bicarbonate production?

Answer 33

HCO3- exits RBCs in exchange for extracellular Cl- on AE1 (anion exchanger isoform 1) , this maintains electroneutrality and also pulls the equilibrium of the reaction to the right.

Question 34

What does the chloride exchanger mean for intracellular [Cl-] in arteries and veins?

Answer 34

Intracellular [Cl-] higher for venous RBCs than for arterial RBCs, as more CO2 in veins

Question 35

How can the red blood cells contain such large amounts of H+?

Answer 35

H+ binds to intracellular buffers (HCO3- would be useless means of transport of co2 without mechanism to buffer H+), mainly Hb. Deoxy-Hb is a better buffer than Oxy-Hb - this underpins the Bohr effect

Question 36

What happens to the bicarbonate at the lungs?

Answer 36

Recombines with H+ to form H2CO3, CA in pulmonary endothelium converts to CO2, which can leave the lungs. Depletion of HCO3- inside RBC means more moves in from plasma via chloride exchanger

Question 37

What is the shape of the CO2 dissociation curve?

Answer 37

Almost linear

Question 38

Explain the Haldane effect

Answer 38

Deoxygenated Hb carries CO2 more readily than oxygenated Hb because it is a weaker acid, so deoxy Hb is a better buffer:

1) More readily binds H+, promoting dissociation of carbonic acid
2) More readily binds weak acid CO2, allowing formation of carbamino CO2.

Therefore, CO2 dissociation curve for Hb at 70% oxygen saturation is above (left) curve at 97% oxygen saturation (as when more oxygenated, more CO2 will dissociate at lower pCO2)

Question 39

Does the Bohr or Haldane effect have a greater quantitative effect?

Answer 39

Haldane

Question 40

Doubling arterial PCO2 (with no alteration of arterial bicarbonate ion concentration) will …

Answer 40

lower arterial pH

Question 41

When metabolism consumes O2 from the blood what does this mean?

Answer 41

O2 content lowered thus PO2 lowered

Question 42

What is the Fick equation for VO2?

Answer 42

CO (Arterial O2 conc - Venous O2 conc)