Oxygen in the blood

Question 1

What are the required properties of a carrier for oxygen?

Answer 1

• Reaction needs to be reversible
• Carrier must associate with O2 at lungs
• O2 must dissociate from carrier at tissues to supply them

Question 2

Describe the structure of haemoglobin

Answer 2

• 2 alpha and 2 beta subunits
• Each subunit has 1 haem group
• Each haem group can bind 1 O2 molecule
• 4 haem groups in Hb can carry 4 O2 molecules total

Question 3

What is the difference between O2 saturation in the blood and PaO2?

Answer 3

• Oxygen saturation is the percentage if haemoglobin bound to oxygen
• PaO2 is the amount of oxygen dissolved in the blood

Question 4

Which states does haemoglobin exist in?

Answer 4

• T state - difficult for oxygen to bind, low affinity for O2
• R state - easier for oxygen to bind, high affinity for O2

Question 5

What is meant by haemoglobin cooperativity?

Answer 5

• Molecular re-arrangement of haem group so that iron is more accessible to oxygen
• Each time an oxygen molecule binds to haemoglobin, it gets easier for each subsequent oxygen molecule to bind

Question 6

What gives the haemoglobin- oxygen dissociation curve its sigmoidal shape?

Answer 6

• As some O2 binds it facilitates further binding
• Curve steepens as pO2 rises
• Saturation of Hb changes greatly over a narrow range
• Curve then flattens as saturation is reached
• Reaction is highly reversible and depends on pO2

Question 7

What does the haemoglobin-oxygen dissociation curve tell us?

Answer 7

• What % of Hb is carrying O2
• Relationship between partial pressure of oxygen and haemoglobin saturation - i.e. shows how much O2 will be bound or given up when moving from one partial pressure to another
• How easy or difficult it is to saturate/desaturate haemoglobin depending on part of curve - work out how changing conditions affects the binding of Hb with O2

Question 8

How soluble is O2 in the blood?

Answer 8

• Poorly soluble, requires a carrier

Question 9

How is oxygen in the blood affected by anaemia?

Answer 9

• Partial pressure of O2 and saturation are normal
• Bur there are fewer RBCs and less Hb for O2 to bind to
• So even if Hb is 100% saturated, there is less O2 bound

Question 10

What does oxygen saturation depend on?

Answer 10

• Partial pressure of O2 in the blood
• This is determined by the alveolar partial pressure of O2

Question 11

Why is it important that the blood is almost 100% saturated over a fairly wide range of pO2?

Answer 11

• There’s a wide safety margin for O2 levels
• O2 saturation drops dramatically past the safety margin level

Question 12

What is normal Hb concentration in the blood?

Answer 12

• 2.2 mmol/L
• Each Hb molecule binds 4 O2 molecules
• O2 content of Hb = 8.8 mmol/L

Question 13

How do we calculate the total oxygen content of the blood?

Answer 13

• Total content = amount of gas chemically bound + amount of gas in free solution
• Amount of O2 dissolved in plasma should be 0.13 mmol/L (because pAO2 is 13.3 kPa)
• Amount bound to Hb = 8.8 mmol/L
• Total = 8.93 kPa

Question 14

What is hypoxaemia?

Answer 14

• Low partial pressure of O2 in arterial blood
• Means that not all Hb is saturated

Question 15

What is hypoxia?

Answer 15

• Low oxygen levels relative to need in body or tissues

Question 16

What can cause hypoxia?

Answer 16

• Can occur due to shock
• Peripheral vasoconstriction can cause peripheral hypoxia
• Tissues using O2 faster than it is delivered e.g. peripheral arterial disease and congestive heart failure with low CO
• Hypoxia secondary to anaemia

Question 17

What does tissue pO2 depend on?

Answer 17

• How metabolically active the tissue
• Typically ~5kPa

Question 18

How low can tissue pO2 get?

Answer 18

• Tissue pO2 must be high enough to drive diffusion of O2 to cells down a partial pressure gradient
• It cannot fall beneath 3 kPa in most capillaries

Question 19

What causes higher capillary density?

Answer 19

• Very metabolically active tissue
• Living at high altitudes
• The higher the capillary density is, the lower pO2 can fall

Question 20

What is mixed venous blood?

Answer 20

• Mixture of blood returning from various tissues
• Over half of O2 is still bound
• PaO2 ~6 kPa

Question 21

What happens when tissue pO2 is low in mixed venous blood?

Answer 21

• More O2 will dissociate from Hb
• This will lower saturation of venous blood
• At low saturation Hb is tense and doesn’t want to bind O2

Question 22

What does a rightward shift of the haemoglobin oxygen dissociation curve suggest?

Answer 22

• Hb has a decreased affinity for O2
• O2 actively unloads

Question 23

What does a leftward shift of the haemoglobin oxygen dissociation curve suggest?

Answer 23

• Hb has increased affinity for O2 and an increased reluctance to release O2

Question 24

What factors affect the haemoglobin oxygen dissociation curve?

Answer 24

• pH
• CO2
• temperature
• 2,3-disphosphoglycerate

Question 25

Explain the Bohr effect

Answer 25

• Acid conditions shift dissociation curve right
• Decreased pH promotes T-state of Hb - Hb has lower affinity for O2
• Metabolically active tissues lower pH

Question 26

Explain how raised temperature affects the haemoglobin oxygen dissociation curve

Answer 26

• Higher temperature shifts curve to the right - more oxygen is released
• Metabolically active tissues lead to higher temperature

Question 27

Explain how increased 2,3-DPG affects the haemoglobin oxygen dissociation curve

Answer 27

• 2,3-DPG is an intermediate of RBC glycolysis
• It is normally rapidly consumed
• In hypoxaemia RBC production of 2,3-DPG is increased
• This causes curve to shift right and O2 unloading in tissues increases

Question 28

Where does maximum unloading of oxygen occur?

Answer 28

• Maximum unloading occurs where tissue pO2 can fall to a low level - the goal is to maintain partial pressure gradient
• Also occurs when environment is more acidic, or temperature is higher

Question 29

What acts as a reserve for when we need extra oxygen?

Answer 29

• Under certain conditions (low pH, high temperature etc.) about 70% bound O2 can be given up
• At rest ~30% O2 extracted from the blood
• The remaining O2 acts as a reserve for when we’re exercising, metabolic stress

Question 30

How does CO affect the haemoglobin-O2 dissociation curve?

Answer 30

• Reacts with Hb to form CO-Hb
• CO has an affinity 200x greater for Hb than oxygen
• Reduces O2 transport
• Also increases affinity of unaffected subunits for O2 so that less O2 is released to peripheral tissues
• Curve shifts left

Question 31

When is CO poisoning fatal?

Answer 31

• If HbCO is >50%

Question 32

What is the clinical presentation of CO poisoning?

Answer 32

• Children at increased risk
• Headache
• Nausea
• Vomiting
• Slurred speech
• Confusion
• Initially few respiratory symptoms

Question 33

What is cyanosis?

Answer 33

• Blueish discolouration due to unsaturated haemoglobin
• Deoxygenated haemoglobin is less red than oxygenated haemoglobin
• Can be peripheral due to poor local circulation
• Or central due to poorly saturated blood in systemic circulation

Question 34

What does pulse oximetry detect?

Answer 34

• Level of Hb saturation
• Difference in absorption of light between oxygenated and deoxygenated Hb
• Only detects pulsatile arterial blood levels
• Can’t detect tissue O2 levels or non-pulsatile venous blood
• Can’t give information about Hb levels
• Less accurate in darker coloured skin

Question 35

What is arterial blood gas?

Answer 35

• The partial pressure of oxygen in arterial blood expressed in kPa
• Also provides sara on PCO2 and pH and bicarbonate
• Depends on amount of dissolved O2

Question 36

How do we measure arterial blood gas?

Answer 36

• requires an arterial blood sample
• usually from radial artery
• invasive