Carriage of O2 and CO2 Flashcards
How is O2 carried in the blood?
- Dissolved in the blood
2. Combined with Hb
How is the amount of gas in solution related to temperature?
More dissolves at low temperatures
How is most O2 carried?
Bound to Hb
Describe the: 1. Primary 2. Secondary 3. Tertiary 4. Quaternary structure of Hb
- 141-146 amino acids per chain
- Globular structure
- ‘Crevice’ for haem and O2 binding
- 4 chains (HbA = 2x alpha and 2x beta)
What does 1 molecule of Hb contain?
- 4x globin chains
- 4x haem groups
- 4x iron atoms and binds 4x O2 molecules
Where is the O2 binding site to haem? Describe ‘T’ and ‘R’ states
In a crevice
- In R ‘relaxed’ state –> O2 can easily access binding site
- In T ‘tense’ state –> O2 less able to access and is pushed out
What is meant by haem ‘cooperativity’?
When 1 O2 binds, it changes the shape of the globin chain which in turn changes the shape of globin chains next to it
This makes it easier and easier for the next O2s to bind until all 4 are attached
How much do we use of the O2 available in blood? Explain this
1/4
Last O2 to bind is hopping on and off as is easiest to gain/lose due to haem cooperativity
What is shape of Hb-O2 dissociation curve? What is reason for this shape?
S-shaped due to cooperativity between chains
Why does Hb-O2 curve flatten at top?
As Hb becomes fully saturated
What is the P50 value on the Hb-O2 curve?
Partial pressure of O2 at which 50% of Hb is saturated with O2 (normally 3.5 kPa)
What is effect of a high temp on Hb-O2 curve? Why?
Curve shifts to right
Due to decreased oxygen affinity of Hb as increased temperature denatures the bond:
- Saturation of Hb with O2 decreases
- More oxygen is available for tissues
Result –> lower Hb saturation with O2 and higher partial pressure of O2 (as more free O2)
What is effect of a low temp on Hb-O2 curve? Why?
Curve shifts to left as affinity of Hb for O2 increases so high saturation
Result –> higher Hb saturation with O2 and lower partial pressure of O2
What is effect of low pH on Hb-O2 curve? Why?
Curve shifts to right
Lower pH causes greater dissociation of O2 from Hb as H+ ions bind to Hb
Allows for enhanced unloading of O2 in metabolically active tissues
Result –> Saturation of Hb with O2 decreases, partial pressure of O2 increases
What is effect of high pH on Hb-O2 curve? Why?
Curve shifts to left as binding affinity of Hb to O2 increases
Result –> saturation of Hb with O2 increases, partial pressure of O2 decreases
What is the Bohr effect?
At greater H+ conc, various amino acid residues (such as histidine) exist mainly in their protonated state which allows them to form salt bridges that stabilise deoxyHb in the T state. The T state has a lower affinity for O2, so with increased acidity, Hb binds less O2
What is effect of 2,3-diphospho-glycerate (DPG) in red cell?
High levels –> shifts curve to right
Low levels –> shifts curve to left
Absence of DPG increases Hb’s affinity for O2
High productions in conditions such as hypoxia
Describe normal HbA
2x alpha chains and 2x beta chains
Describe normal HbF
2x alpha chains and 2x gamma chains
What occurs in thalassaemia?
Genetic abnormality where you cannot produce a functioning version of one of the chains
Alpha thalassaemia –> can’t produce alpha chains, often unsurvivable
Beta thalassaemia –> can’t produce beta chains, tend to just keep foetal Hb and survive
What happens in sickle cell disease?
Single amino acid goes wrong in position 6 on beta chain (single nucleotide substitution of A to T). Becomes Valine instead of Glutamic Acid. HbS forms.
What happens in sickle cell disease if patients become deoxygenated?
HbS molecules stick together which causes RBCs to ‘sickle’ which stick together and cause blockages in small blood vessels –> painful
What happens when Fe3+ is formed instead of Fe2+?
Hb becomes methaemoglobin (metHb)
What is problem with metHb?
metHb doesn’t carry O2 so O2 carrying capacity is reduced
What happens when CO binds to Hb?
Binds with higher affinity than O2. Blocks O2 binding sites
Carboxyhaemoglobin gives patients deceptively pink and healthy appearance.
What is a buffer?
A solution that can minimise changes in the free H+ conc and therefore in pH
What is equation for pH?
pH = log10[H+]
Acid H+ + base
What is effect of adding H+ ions/alkali?
Adding H+ –> shifts equilibrium to left (to remove extra H+)
Adding alkali –> Will form water which will remove H+ ions to shifts equilibrium to right (to replace H+ ions)
What are most important buffers in the blood? What is purpose of them?
Bicarbonate & Hb
Ensure blood pH is very tightly controlled (7.35-7.45)
Why are proteins with lots of histadine amino acids good buffers?
Histadine has side chain that acts as buffer
How is CO2 carried in blood?
- Dissolved in blood
- Carbamino compounds
- As carbonic acid/bicarbondate
How is majority of CO2 carried in blood?
As carbonic acid/bicarbonate
How does CO2 form carbamino compounds?
Combines with Hb directly (loose chemical bond)
Bound to amino groups on proteins to form carbamino compounds (1 Hb can carry 4x CO2 molecules)
How is CO2 carried as carbonic acid/bicarbonate?
As blood goes through the capillary, CO2 from tissues diffuses into blood
- CO2 combines with H2O to form carbonic acid (H2CO3)
- This is accelerated by carbonic anhydrase
- Carbonic acid breaks down into H+ ions and HCO3- ions very quickly
- Leaves a lot of HCO3- in RBC
H+ ions are buffered by Hb
How does red cell get rid of excess HCO3-?
Cell has ion channel in cell surface that ejects HCO3- in exchange for chloride ion (Hamburger shift)
This allows equation to keep going right to remove CO2
Why are arterial and venous curves different in regards to CO2 dissociation?
Due to ability of deoxygenated blood to carry more CO2 than oxygenated blood –> Haldane effect
What is the relationship between blood pH, CO2 and HCO3- described by?
Henderson-Hasselbalch equation
What is acidosis?
Increased acidity in blood and tissues. pH < 7.35
What is alkalosis?
Increased alkalinity in blood and body tissues. pH > 7.35
What is the amount of CO2 controlled by?
The respiratory system
Blood pH regulates ventilation and so controls partial pressure of CO2
Is respiratory compensation rapid or slow response?
Rapid response
How is bicarb concentration in the body controlled?
By the renal system
Excretion of H+ in urine is controlled by pH
(Metabolic acidosis/alkalosis)
How can results show a respiratory acidosis? What is it caused by?
High PCO2, normal HCO3- (high HCO3- if renal compensation occurs).
Respiratory/ventilation failure
How do kidneys compensate for respiratory acidosis?
Higher HCO3- levels to increase pH. Kidneys reabsorb more bicarbonate to compensate
How can results show a metabolic acidosis? What is it due to?
Low HCO3-, normal PCO2 (low PCO2 if respiratory compensation occurs)
Renal failure causes too little bicarbonate, diabetic ketoacidosis, shock, poor perfusion and tissues produce lactic acid instead
How does respiratory system compensate for metabolic acidosis?
Lungs breathe more to get CO2 to fall
Is renal compensation rapid or slow?
Slow response (hours)
How can results show respiratory alkalosis? What is it caused by?
Low PCO2, normal HCO3-
Hyperventilation (anxiety, iatrogenic)
What results show metabolic alkalosis? What is it caused by?
Normal PCO2, high HCO3- (high PCO2 if respiratory compensation occurs)
Loss of H+ e.g. vomiting, abuse of antacid remedies
Can compensation get pH back to normal?
No, only helps
