Role of haemoglobin in oxygen delivery to tissue Flashcards
Describe oxygen delivery system to tissues
Oxygen diffuses into from blood to tissues to cells via oxygen pressure gradient.
Pressure of arterial PO2
100 mmHg
Pressure of interstitial fluid PO2
40 mmHg
Pressure of intercellular PO2
25 mmHg
Haemoglobin carries?
15 mL of oxygen per gram
Describe haemoglobin function
- Hb increases blood oxygen carrying capacity by 60x
- Without Hb, not enough oxygen can dissolve in blood.
What is haemoglobin?
Metalloprotein that binds to oxygen
_____ of blood oxygen is bound to Hb
98.5%
Composition of haemoglobin?
Made of 4 polypeptide chains alpha-gamma-beta, each with heme group (iron molecule in a porphyrin group)
How many iron molecules are bound to each oxygen molecule?
Each iron molecule can reversibly bind to one oxygen molecule (4 per haemoglobin)
Haemoglobin A (Hb A) is?
Adult haemoglobin with 2 alpha-chains and 2 beta-chains
Haemoglobin F (Hb F) is?
Fetal Hb with 2 alpha-chains and 2 gamma-chains; higher oxygen binding affinity; replaced by Hb A at 6 months.
Define “cooperative binding”
When one molecule of oxygen binds to haemoglobin, the conformation changes to R state and Hb affinity for more oxygen increases.
T state of haemoglobin?
T state = Deoxygenated state; tense; low affinity for oxygen
R state of haemoglobin?
R state = oxygenated state; relaxed; high affinity for oxygen
Cooperative binding explains?
Explains the oxygen-haemoglobin dissociation curve
Hb carrying capacity is dependent on?
Depends on surrounding PO2 of blood.
Describe the flat curve at PO2 > 70 mm Hg
Increasing or decreasing PO2 has little effect (e.g. breathing high [O2] air or high altitude)
Describe steep curve at PO2 < 50 mmHg
Small change in PO2 has large effect on binding.
- This is a range of PO2 of capillaries
- Venous capillary blood is about 75% saturated.
- Unbinding from Hb allows more Oxygen to diffuse into tissues.
Factors that affect oxygen-haemoglobin curve: lower binding affinity
- Bohr effect: increase in partial pressure of carbon dioxide, lower pH (increase acidity)
- Increase temperature
- Increase 2,3-biphosphoglycerate (BPG)
What is BPG (2,3-Biphosphoglycerate)?
BPG = component of RBC; increased levels of BPG in chronic hypoxia (reduce oxygen)
Lower binding affinity allows for?
Allows more oxygen to unload at same partial pressure of oxygen.
Occurs when oxygen is needed in tissue - i.e. in sites with increased metabolic activity
Hb F has higher affinity which?
Shifts O2-Hb curve left.
Polycythaemia is when?
Hb = 20
Normal blood O2-Hb level
Hb = 15
Anaemia blood O2-Hb level
Hb = 10
Carbon monoxide poisoning happens by?
- CO binds at oxygen binding site of Hb
- CO-induced hypoxia does NOT cause breathlessness
Describe the steps in CO binding at oxygen binding site of Hb
- Binds with 200x higher affinity
- PCO2 that is 1/200 PO2 will bind with 50% of Hb sites
- Blood PO2 will be normal but Oxygen content of blood will be very low
CO-induced hypoxia does NOT cause breathlessness because?
- PCO2 levels triggers chemoreceptors but PCO2 are normal (CO2 binds to different site of Hb)
- PO2 levels of blood have minor chemoreceptor role, but PO2 levels are normal.
Define hypoxia
Diminished supply of oxygen below metabolic requirements
Hypoxic hypoxia
Failure of oxygen to reach blood in lungs
Stagnant hypoxia
Failure to transport sufficient oxygen due to inadequate blood flow
Anaemic hypoxia
Oxygen carrying capacity of blood inadequate
Histotoxic hypoxia
Failure of tissues to utilize oxygen
Carbon dioxide is transported in 3 forms:
- Dissolved CO2 (proportional to PCO2) - 10%
- Carbamino haemoglobin (HbCO2) - 20%
- Bicarbonate ions (HCO3) - 70%
Carbaminohaemoglobin (HbCO2)
- Different binding site than oxygen
- CO2 has higher affinity for reduced Hb (i.e. after unloading of oxygen) - Haldane effect
Bicarbonate ions (HCO3)
- Conversion accelerated by carbonic anhydrase in RBC
- Following reaction occurs inside RBC: CO2 + H2O H2CO3 H+ + HCO3-
- HCO3 easily diffused through RBC membrane
- H+ cannot diffuse out and accumulates inside RBC
- H+ has higher affinity for reduced Hb (i.e. after unloading of oxygen) - Haldane effect
- Hb is very effective buffer by reducing free H+ (i.e. increase pH)
What does Bohr effect and Haldane effect work to?
They work to facilitate oxygen release, and carbon dioxide and hydrogen ion uptake in tissues.
Bohr effect
pH decrease or CO2 increase shift Hb-O2 dissociation curve right
Haldane effect
Removal of oxygen from Hb increases the affinity for CO2 and H+