Oxygen in the blood Flashcards
What are the required properties of a carrier for oxygen?
- Reaction needs to be reversible
- Carrier must associate with O2 at lungs
- O2 must dissociate from carrier at tissues to supply them
Describe the structure of haemoglobin
- 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
What is the difference between O2 saturation in the blood and PaO2?
- Oxygen saturation is the percentage if haemoglobin bound to oxygen
- PaO2 is the amount of oxygen dissolved in the blood
Which states does haemoglobin exist in?
- T state - difficult for oxygen to bind, low affinity for O2
- R state - easier for oxygen to bind, high affinity for O2
What is meant by haemoglobin cooperativity?
- 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
What gives the haemoglobin- oxygen dissociation curve its sigmoidal shape?
- 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
What does the haemoglobin-oxygen dissociation curve tell us?
- 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
How soluble is O2 in the blood?
- Poorly soluble, requires a carrier
How is oxygen in the blood affected by anaemia?
- 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
What does oxygen saturation depend on?
- Partial pressure of O2 in the blood
- This is determined by the alveolar partial pressure of O2
Why is it important that the blood is almost 100% saturated over a fairly wide range of pO2?
- There’s a wide safety margin for O2 levels
- O2 saturation drops dramatically past the safety margin level
What is normal Hb concentration in the blood?
- 2.2 mmol/L
- Each Hb molecule binds 4 O2 molecules
- O2 content of Hb = 8.8 mmol/L
How do we calculate the total oxygen content of the blood?
- 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
What is hypoxaemia?
- Low partial pressure of O2 in arterial blood
- Means that not all Hb is saturated
What is hypoxia?
- Low oxygen levels relative to need in body or tissues
What can cause hypoxia?
- 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
What does tissue pO2 depend on?
- How metabolically active the tissue
- Typically ~5kPa
How low can tissue pO2 get?
- 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
What causes higher capillary density?
- Very metabolically active tissue
- Living at high altitudes
- The higher the capillary density is, the lower pO2 can fall
What is mixed venous blood?
- Mixture of blood returning from various tissues
- Over half of O2 is still bound
- PaO2 ~6 kPa
What happens when tissue pO2 is low in mixed venous blood?
- 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
What does a rightward shift of the haemoglobin oxygen dissociation curve suggest?
- Hb has a decreased affinity for O2
- O2 actively unloads
What does a leftward shift of the haemoglobin oxygen dissociation curve suggest?
- Hb has increased affinity for O2 and an increased reluctance to release O2
What factors affect the haemoglobin oxygen dissociation curve?
- pH
- CO2
- temperature
- 2,3-disphosphoglycerate
Explain the Bohr effect
- Acid conditions shift dissociation curve right
- Decreased pH promotes T-state of Hb - Hb has lower affinity for O2
- Metabolically active tissues lower pH
Explain how raised temperature affects the haemoglobin oxygen dissociation curve
- Higher temperature shifts curve to the right - more oxygen is released
- Metabolically active tissues lead to higher temperature
Explain how increased 2,3-DPG affects the haemoglobin oxygen dissociation curve
- 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
Where does maximum unloading of oxygen occur?
- 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
What acts as a reserve for when we need extra oxygen?
- 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
How does CO affect the haemoglobin-O2 dissociation curve?
- 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
When is CO poisoning fatal?
- If HbCO is >50%
What is the clinical presentation of CO poisoning?
- Children at increased risk
- Headache
- Nausea
- Vomiting
- Slurred speech
- Confusion
- Initially few respiratory symptoms
What is cyanosis?
- 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
What does pulse oximetry detect?
- 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
What is arterial blood gas?
- 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
How do we measure arterial blood gas?
- requires an arterial blood sample
- usually from radial artery
- invasive
