Week 1 Oxygen Transport Flashcards
Outline the reasons for oxygen transport in the blood
- Oxygen is necessary for life! In the presence of oxygen 1 molecule of glucose will produce 38 ATP compared to only 2 molecules without.
- Blood carries oxygen to tissues, its utilisation must match its delivery
- Oxygen usage by the body varies on our level of activity - resting consumption 250ml/min
- Oxygen has very poor solubility in blood (only 3ml/L dissolved at alveolar pO2 of 13.3kPa). (And assumes all extracted).
- If dissolved oxygen was only method of oxygen transport would need to supply tissues with 80 L of blood per min
- Actual cardiac output only 5 L per min therefore need a reaction that is able to carry more O2 per L of blood.
A reaction is required to carry more oxygen in the blood
- What does this reaction need to be?
- This reaction needs to be rapidly reversible and able to respond to a wide range of demands
Describe the structure of haemoglobin
- Haemoglobin is a tetramer made up of 2 alpha and 2 beta globulin chains
- Each alpha/ beta globulin chain has a central heme group embedded within it.
- Heme is a porphyrin compound made up of a porphyrin ring with a central Fe2+ ion (Iron is in its Ferrous form).
- Oxygen can only bind when it is in its ferrous form.
- Interaction of O2/ Fe2+ and porphyrin gives blood its red colour when saturated with O2 and is purple without oxygen.
What is the main form of haemoglobin in an adult?
Haemoglobin A is the main form in the adult
What two states can haemoglobin exist in?
Describe how this occurs at the molecular level
Relate this to the oxygen binding curve.
- Haemoglobin can exist in a (T) Tensed form and a (R) relaxed form.
-
Tensed form:
- Hb tetramer units are tightly bound, they can only leave the tensed form if they all leave it together
- Shape of heme in the tensed state sterically inhibits the approach of oxygen
- Quaternary structure inhibits O2 binding.
- Empty Hb has very low affinity for O2- notoriously hard to bind the first O2 molecule.
- Binding of first O2 molecule requires a threshold minimum of pO2.
-
Relaxed form:
- Oxygen binds to the Fe2+ of a heme group, altering its structure to make it more receptive to further oxygen binding
- When enough O2 binds all 4 heme groups snap into the relaxed state whether or not they are bound to oxygen.
- Haemoglobin quaternary structure is modified and becomes open
- Further binding of oxygen increases haemoglobin O2 affinity- reflects cooperativity between binding sites.
- The oxygen dissociation curve is sigmoidal in shape as this reflects the cooperativity between binding sites:
- At low pO2, increases in pO2 produce small increases in O2 saturation of haemoglobin. Most haemoglobin is in the tensed state with low affinity for oxygen.
- At intermediate pO2 the saturation of haemoglobin begins to increase more steeply with increasing oxygen tension, reflecting increased O2 affinity as more Hb molecules shift to relaxed state.
- At high PO2 saturation reaches a plateau as most haemoglobin is in its relaxed form and reaching full saturation of oxygen.
What is the total oxygen content of the blood formed by?
- The amount bound to haemoglobin (98 %)
- The amount dissolved in plasma (2%)
What happens to chemical binding above a given high pO2?
At this point, what does the amount of oxygen carried in the blood now depend on?
- Above a given high pO2 oxygen saturation of haemoglobin becomes fully saturated- chemical binding has reached a maximum.
- The amount of oxygen carried in the blood now depends on the amount of available haemoglobin
What is the y axis of the oxygen saturation curve normally expressed as?
- Normally expressed as a percentage of the total amount of oxygen bound at full saturation
What is independent of haemoglobin concentration?
- Ability of oxygen to saturate haemoglobin is actually independent of its concentration.
Describe typical values associated with the oxygen dissociation curve
- Above 8kPa haemoglobin tends to be around 90% saturated and is in the plateau portion of the curve.
- At 3.5 kPa haemoglobin tends to be 50% saturated
- Below 1kPa of PO2 haemoglobin is barely saturated.
- Saturation changes markedly over a narrow range in the central portion of the sigmoid curve.
Describe the typical partial pressure of oxygen in an alveolus
How does this relate to the saturation of haemoglobin with oxygen?
How does this relate to oxygen delivery to the tissues if:
Each gram of haemoglobin can combine with 1.34 ml of O2.
Typical haemoglobin content is 150g/L blood
- Partial pressure of oxygen in a typical alveolus is 13.3 kPa- related to plateau of the dissociation curve, haemoglobin virtually fully saturated at 95%.
- Multiply 1.34 ml of O2 with the haemoglobin content of 150g/L of blood:
- Means 200 ml of O2 carried per L of blood.
- under resting conditions average oxygen consumption is 250ml/min
- CO= 5L/ min
What is the typical partial pressure of oxygen in the tissues?
How does this relate to the oxygen saturation of haemoglobin?
How does the saturation of haemoglobin change from the pulmonary circulation to the tissues?
How does this relate in real numbers given that the total amound of O2 carried by the blood is around 200ml/L
- Typical PO2 in tissues is around 6kPa.
- Oxygen saturation of haemoglobin is around 65% in the tissues
- This has changes from around 95% in the pulmonary circulation, haemoglobin has given up 30% of its oxygen.
- In terms of real numbers:
- 0.3 x 200ml/L = 60 ml of O2 delivered per L of blood.
What is the typical partial pressure of oxygen in venous blood?
How does this related to the saturation of haemoglobin in venous blood?
How can the oxygen saturation change under different conditions?
- Typical partial pressure of oxygen in venous blood is inbetween 4-5 kPa.
- The oxygen saturation of haemoglobin still tends to be above 50% in venous blood under resting conditions.
- Under conditions of higher metabolic rate, haemoglobin can still donate more of its oxygen to the respiring tissues- there is some reserve.
What would a lower partial pressure of oxygen in the tissues mean for oxygen dissociation from haemoglobin?
- A lower partial pressure of oxygen in the tissues would mean there is a steeper diffusion gradient from the haemoglobin in RBC’s to the tissues
- Oxygen will dissociate more readily
- As oxygen dissociates from haemoglobin, haemoglobin’s affinity for oxygen drops further, facilitating release to the tissue.
- However there is a limit on how low Oxygen partial pressure can drop in tissues before diffusion to cells is compromised. (If O2 partial pressure is too low in tissue, diffusion becomes insufficient to deliver enough oxygen).
What is the partial pressure of oxygen in the tissues compared to arterial blood?
What sort of tissues can tolerate low pO2 better than others and why?
- Partial pressure of oxygen in tissues is around 6kPa compared to 13.3 kPa in the arterial blood- creates concentration gradient that drives oxygen into the tissues.
- Tissues with a high capillary density can tolerate low pO2 better than others- e.g heart muscle
- This is because it reduces the distance to diffusion from the capillary to the tissue and increases the surface area available for exchange which allows maintenance of an effective gradient from the capillaries and cells.
what does the configuration of haemoglobin depend on?
Give examples of stimuli that alter its configuration.
- The configuration of haemoglobin is reliant upon its environment.
- Examples of conditions which alter the configuration (and therefore state (tensed/ relaxed) of haemoglobin include:
- Increased temperature
- Acidic pH (low pH)
- Increased partial pressure of CO2
- 2,3- Diphosphoglycerate (DPG)
- All the above stimuli shift haemoglobin from its relaxed state to its tensed state with lower affinity for oxygen
- This means oxygen is more readily released where it is needed as all the above conditions occur in respiring tissues.
- Shifts the oxygen dissociation curve to the right- for every pO2, haemoglobin is now less saturated as more of it is in its stabilised tensed form with low affinity for oxygen.
What is the Bohr effect?
What is it due to?
What does this allow physiologically?
Why do metabolising tissues promote the Bohr effect?
How much Oxygen is given up at metabolising tissues?
- Describes the right ward shift in the oxygen dissociation curve with increasing partial pressure of CO2 and acidic pH as seen in respiring tissues.
- It is due to H+ and CO2 binding to haemoglobin, which promotes O2 release and stabilised haemoglobin in its tensed state.
- Promotes the release of oxygen where it is required.
- Metabolising tissues have high partial pressure of CO2 and a lower pH/ more acidic pH due to lactic acid production.
- Haemoglobin in metabolising tissues has lower oxygen affinity and can release up to 70% of its bound oxygen.
What is the opposite of the Bohr Effect?
How does this come about?
Where does this opposite effect have its uses?
- The Haldane effect is the opposite of the Bohr effect and describes how increasing oxygen binding to haemoglobin promotes H+ and CO2 release.
- This is due to oxygen binding altering quaternary structure.
- This has its uses at the level of the pulmonary capillaries where it promotes the release of CO2 to the alveoli for excretion.
What are the adaptations to chronic hypoxia?
Adaptations to chronic hypoxia:
- Increase in erythropoetin production via the kidneys leading to an increase in erythrocyte production
- Increase in tissue capillary density
- Increase in 2,3-DPG produced in erthyrocytes
- Increased ventilation
what can cause chronic hypoxia?
Various causes:
- Anaemia
- Low haemoglobin
- Low blood volume
- Poor blood flow
- Pulmonary disease
