Oxygen Transport

Question 1

How much ATP does glucose produce aerobically and anaerobically?

Answer 1

Aerobic: ~38 ATPs

Anaerobic: 2 ATPs

Question 2

How does oxygen get to tissues and then, how is it used?

Answer 2

Blood carries O2 to tissues

O2 delivery must match utilisation

O2 travels to tissues down the “oxygen cascade”

Question 3

How does the oxygen cascade work?

Answer 3

As O2 moves from the atmosphere, to the alveoli/capillaries + then to mitochondria of tissues, O2’s partial pressure will drop so O2 will travel down this cascade

The O2 difference at the alveolar arterial is usually small but may be increased in lung disease

Question 4

What would happen if dissolved oxygen was the only method of transport to tissues?

Answer 4

Resting O2 consumption is 250ml/min + it has poor solubility in water (~3ml/L dissolved at alveolar pO2 of 13.3 kPa)

So tissues would need to be supplied with > 80L/min blood at rest when CO ~5L/min

Question 5

What is oxygen binding? What are the problems with it?

Answer 5

Chemical reaction needed to transport more O2 per L of blood; many substances react with O2 so getting it into blood is not hard BUT extracting sufficient amounts at tissue level is the challenge so this requires a rapidly reversible reaction that can respond to wide range of demand

Question 6

What is haem?

Answer 6

Porphyrin compound coordinated to a Fe atom (in ferrous form; Fe2+)

Binds O2 reversibly in blood + goes red when fully saturated or purple when unbound

Question 7

What is haemoglobin?

Answer 7

A tetramer made up of 2 α + 2 β globin chains - each coiled polypeptide chain has 1 haem + 1 globin component -> quaternary structure

Hb A = main adult form

Question 8

What is the relevance of haemoglobins structural features?

Answer 8

Structure influenced by various inputs + its modification alters the O2 affinity of the molecule

Question 9

What are the 2 forms haemoglobin can exist as?

Answer 9

Relaxed: open + receptive structure allowing O2 to access haem groups = higher O2 affinity

Tense: inhibits O2 binding so binds O2 500x less avidly than in relaxed form

Question 10

What happens to haemoglobins configuration when there is low environmental pO2?

Answer 10

Hb is in its tense form + no O2 is bound as it is hard to bind the 1st O2 molecule - initial binding requires a threshold minimum pO2

Question 11

What happens to haemoglobins configuration when environmental pO2 starts to rise?

Answer 11

As Hb binds O2 to 1 chain, its structure is modified + open becoming the relaxed form so binding next O2 molecule is easier + reflects cooperativity between O2 binding sites -> binding becomes easier as more O2 is bound

Question 12

What is the dissociation curve?

Answer 12

Represents the reversibility of O2 binding

X axis = pO2 (kPa/mmHg)
Y axis = % of total amount of O2 bound at full saturation

Total O2 content = bound + dissolved (ml of O2/dL of blood)

Question 13

What is O2 saturation?

Answer 13

As shown by dissociation curve, chemical binding becomes saturated/plateaus above given pO2

Amount of O2 bound then depends on how much Hb is available however, saturation is INDEPENDENT of [Hb]

Question 14

What happens to the bloods O2 saturation + concentration in anaemia?

Answer 14

O2 saturation remains the SAME

Less [Hb] so less [O2]

Question 15

What can the O2 dissociation curve reveal?

Answer 15

How much O2 will be bound/given up when blood is moved between areas with different pO2’s e.g. from lungs to tissues or vice versa

Question 16

Why does the O2 dissociation curve have its typical sigmoid shape?

Answer 16

At first, relationship between pO2 + binding is poor

Binding changes configuration, increasing O2 affinity + facilitates further binding so curve steepens rapidly as pO2 rises

Saturation then occurs so the curve will level out + plateau

Question 17

What are the O2 dissociation curve anchor points?

Answer 17

1 kPa pO2 = Hb virtually unsaturated

3.5 kPa pO2 = Hb half saturated

8 kPa pO2 = Hb almost fully saturated e.g. alveolar (pO2 of 13.3 kPa)

Question 18

What is the typical O2 content of fully saturated blood of a healthy individual?

Answer 18

Each gram of Hb can combine with 1.34ml of O2

So, for a typical Hb of 150g/L, O2 content in fully saturated blood is 200ml/L (includes dissolved O2 too)

Question 19

What is the approximate amount of O2 delivered to tissues?

Answer 19

Tissue PO2 typically 6kPa at rest when Hb is 65% saturated

Change in binding as moved from tissues to lungs (95% saturated) = 95 - 60 = 30% O2 given up by Hb at tissues

0.3 x 200ml/L (O2 content in full saturated blood) = 60ml O2 delivered per L of blood

Question 20

Describe how venous blood haemoglobin keeps a oxygen reserve for when tissue demand increases.

Answer 20

Venous blood returns to heart after supplying tissues

In resting state, still has > 1/2 O2 bound

At tissues, Hb could possibly release more O2 if required for metabolism

So there is O2 reserve that can be mobilised if demand increases

Question 21

What happens to the pO2 and therefore, the [O2] at the level of the tissues?

Answer 21

If tissue pO2 is lower, more O2 is given up by Hb as it diffuses down the increased gradient more quickly

Hb has less affinity for O2 as no. of molecules bound decreases however, there is a limit to how low tissue [O2] can drop before diffusion to cells is compromised

Question 22

What tissues can tolerate a greater drop in pO2 and why?

Answer 22

Tissues with high capillary density can tolerate greater falls in pO2 e.g. heart muscle because diffusion occurs across shorter distance + higher SA allows maintenance of effective gradient between capillaries + cells

Question 23

Why does the O2 dissociation curve shift?

Answer 23

Configuration of Hb depends on environment e.g. pH + temp so curve will shift along x-axis depending on whether the O2 affinity has increased or decreased

Question 24

What factors shift the O2 dissociation curve to the right? Why?

Answer 24

Acidity
Increased temperature
Increased CO2
Increased 2,3-DPG/BPG

These factors decrease O2 affinity of Hb by stabilising tense form

Question 25

Why would we want to shift the O2 dissociation curve to the right when there is high [2,3-DPG]?

Answer 25

2,3-DPG increases in RBCs in response to hypoxia so O2 is not bound due to low O2 affinity

Question 26

What is the Bohr effect?

Answer 26

O2 dissociation curvw shifts along x-axis in response to acidic conditions; due to H+ ions + CO2 binding which both stabilise Hb’s tense form = at any given pO2, Hb binds less O2 as affinity has decreased -> O2 released more easily in tissues where pH is more acidic + CO2 in higher concentration - Hb releases up to 70% of bound O2

Question 27

What is the Haldane effect?

Answer 27

Increasing O2 binding to Hb in lungs (pulmonary capillaries) reduces affinity for CO2 + H+ ions modifying Hbs structure -> more CO2 being offloaded at lungs (opposite of Bohr effect)

Question 28

What is pH low in metabolising tissues?

Answer 28

Increased production of lactic acid + CO2 in tissues that are metabolically active + need O2 due to anaerobic metabolism

Question 29

What is hypoxia? What can cause it?

Answer 29

Reduced availability of O2 to body tissues

Causes:

• Low blood volume
• Anaemia
• Low Hb
• Poor blood flow
• Pulmonary disease

Question 30

In chronic hypoxia, the body will trigger various adaptive responses to attempt to increase O2 delivery to tissues. What are some examples of this?

Answer 30

Increased EPO = increased RBC production
Increased tissue capillary density
Increased 2,3-DPG/BPG levels
Increased ventilation