Lecture 6 - Oxygen Transport

Question 1

Describe the structure of haemoglobin (Hb)

How many molecules of oxygen can Hb bind?

Answer 1

• 2 alpha & 2 beta subunits (tetramers)

- Each subunit has a haem group with Fe in it. 1 x O2 binds to each haem group so 1 Hb can bind 4 x O2 molecules

Question 2

What are the axis’ on a Hb-dissociation curve & what does it tell us?
What is oxygen saturation (SaO2)

Answer 2

• Y axis = percentage saturation (sO2 %), X-axis = Oxygen kPa
• Tells us how changes in PO2 change Hb saturation
• Oxygen saturation is the % of Hb that is fully saturated with oxygen (hence gives no indication of how much Hb there is in blood)

Question 3

Why does the curve in a Hb-dissociation curve rise steeply as PO2 rises?
Why does this curve flatten at higher PO2 levels?
What is the shape of this curve?

Answer 3

• Initially curve is shallow, but as Hb binds more O2, Hb facilitates further binding (co-operativity effect). This is due to molecular re-arrangement of haem group so iron is more accessible for oxygen (enhancing affinity).
• Curve flattens as Hb saturation is reached. This gives a sigmoidal curve

Question 4

How are the names for the low affinity and high affinity states of Hb for oxygen?
When are these states useful?

Answer 4

Low affinity = Tense/T state - difficult for oxygen to bind, easy to dissociate. This is when PO2 is low, useful for unloading at respiring tissues.

High affinity = Relaxed/R state - easier for oxygen to bind. Useful when PO2 is high, i.e.: for loading in the lungs.

Question 5

What is the significance of “Zone A” - the wide range of oxygen pressures at which 100% saturation is achieved?

Answer 5

There is a wide range of oxygen pressures at which we can be fully saturated, i.e.: when climbing up a mountain we will be okay for a while … until, PO2 drops below safety zone (into zone B), i.e.: at the top of mt everest

Question 6

How can we calculate oxygen content on Hb of arterial blood using Hb concentration?

Answer 6

• Normal Hb concentration is 2.2mmol/L, each Hb binds 4 O2, so 2.2 x 4 = 8.8 mmol/L O2 on haemoglobin.

Question 7

How does PO2 in respiring tissues affect the PO2 of mixed venous blood?
What is the typical value for PO2 in metabolically active tissues?

Answer 7

• Typical tissue has PO2 of 5kPa, causing Hb saturation to drop to 65% (so 35% of oxygen given off), therefore Hb is in tense state.
• The lower the tissue PO2, the more oxygen is unloaded from Hb and the lower the saturation will be in the mixed venous blood, reducing PVO2.

Question 8

How do tissues compensate for an extremely low PO2 in order to allow O2 from diffuse to into cells?

Answer 8

They will have a higher capillary density. This reduces diffusion distance and compensates for decreased partial pressure/pressure gradient. E.g..: in very metabolically active tissue (heart) or in people living at high altitude.

Question 9

What is the effect of a low pH/increased H+ concentration (Bohr effect) on the Hb-dissociation curve?

Answer 9

• Acidic condition shift curve to right
• Increased pH promotes T-state, favouring unloading with a lower affinity for O2
• This occurs in metabolically active tissues

Question 10

What is the effect on increasing temperature on a Hb-dissociation curve?
How much oxygen is extracted from blood at rest vs how much can be extracted under very low PO2 conditions such as in

Answer 10

• Higher temperatures shift curve to right, places Hb in T-state, favouring unloading
• Useful as metabolically active tissues have higher temperature
• Under resting conditions roughly 30% is extracted, this can rise to 70% in times of exercise or metabolic stress (i.e.: burns) without having to increase CO, so acts as a reserve.

Question 11

When is 2,3-DPG/BGP produced?

What is the effect of 2,3-DPG on Hb-dissociation curve?

Answer 11

• Intermediate of RBC glycolysis, usually rapidly consumed but in hypoxia production increases.
• Shifts curve to right, places Hb in T-state and favours unloading

Question 12

Why is CO poisoning such a problem?

What are the symptoms?

Answer 12

• CO has 200x greater affinity for Hb than O2, forming CO-Hb.
• Causes increase in affinity of the UNAFFECTED subunits of Hb, and therefore reduces oxygen release in peripheral tissue. Fatal if CO-Hb >50%
• Headache, nausea, vomiting, slurred speech, confusion
• CO poisoning does NOT decrease PaO2, so cannot be detected with O2 sats monitor or ABG.

Question 13

What is cyanosis?

What is the difference between peripheral and central cyanosis?

Answer 13

• Cyanosis = bluish colouration due to unsaturated Hb (>85-90%)
• Peripheral = in fingers, feet, tip of nose and occurs due to decreased perfusion to peripheries, so maximum amount of oxygen is being extracted, leading to increased desaturated Hb.
• Central = in mouth, lips, tongue etc and occurs due to poorly saturated blood in systemic circulation - essentially hypoxaemia.

Question 14

What is used to measure Hb saturation non-invasively & how does it work?
What else can be used?

Answer 14

• Pulse oximetry, detects absorption of light between oxygenated & deoxygenated Hb. Can only detect pulsatile arterial blood levels, can’t give information on Hb levels and less accurate in darker skin.
• Arterial blood gas machines (ABG’s) … more to follow.

Question 15

What is the difference between hypoxaemia + hypoxia?

Answer 15

Hypoxaemia = Low PaO2 in arterial blood
Hypoxia = Low oxygen levels relative to need in body or tissues