Week 8

Question 1

What determines oxygen diffusing capacity in the lungs?

Answer 1

• Surface area
• capillarity
• Barrier thickness
• Volume of lungs

Question 2

What determines oxygen diffusion capacity in peripheral tissues?

Answer 2

• Endothelium thickness
• Capillarity
• Mitochondrial location
• cell size
• hematocrit concentration

Question 3

CO2 Transport

Answer 3

• Occurs in the opposite direction
• Venous PCO2 affected by blood flow and metabolism (at given blood flow VCO2 is greater with greater metabolic rate)
• Blood CO2 content is determined by PCO2 haemoglobin and carbonic anhydrase

Question 4

Haemoglobin

Answer 4

• Tetramer composed of 4 subunits (2 alpha-globin chains and 2 beta globin chains)
• Each subunit is structurally similar to myoglobin a monomeric O2 binding protein in muscle
• Each subunit contains a Fe2+ containing heme ring structure that binds 1 O2

Question 5

Haemoglobin-O2 binding curve

Answer 5

• sigmoidal shape due to cooperative O2 binding (binding of 1 O2 leads to change is protien conformation that facilitates the binding of additional O2 - T to R)
• Interactions between subunits contribute to cooperativity. It is not exhibited by monomeric globin’s
• R state is more open and relaxed

Question 6

Haemoglobin-O2 hill equation

Answer 6

Haeoglobin saturation= PO2^n/(P50^n+PO2^n)
- Where n describes cooperativity
- P50 is a metric of Hb-O2 affinity
- With no cooperativity, the equation becomes like the standard michaelis-menten equation

Question 7

Negative Allosteric Modifiers

Answer 7

• RBC contain ligands that bind Hb and decrease Hb-O2 affintiy
• Hb-O2 affinity of whole body is much lower than isolated Hb
• Ligands usually bind far from heme (N- and C-termini of globin chains, central cavity of tetramer)
• These ligands favor and are bound in T-state, released in R-state

Question 8

Haemoglobin and blood O2 content

Answer 8

Most of the O2 in blood is bound to haemoglobin due to the low solubility of O2 in water/plasma
- Hb-O2 saturation and the concentration of Hb in the blood determines blood O2 content
- Hb is almost fully saturated in blood leaving the lungs and partially deoxygenated after leaving peripheral tissues

Question 9

Bohr Effect

Answer 9

• CO2 and H+ are also Hb ligands and negative allosteric modifiers of Hb-O2 binding
• CO2 partial pressures increase and pH decreases as blood travels through capillaries
• Bohr effect amplifies the release of O2 form Hb in peripheral tissues

Question 10

Temperature Effect

Answer 10

Increased temperature decreases Hb-O2 binding

Question 11

What causes a rightward shift in the hemoglobin saturation curve

Answer 11

1. Increase in H+
2. Increase in CO2
3. Increase in temperature

Question 12

How does the hemoglobin saturation curve in atrial blood compare to venous blood at rest and at exercise

Answer 12

Venous blood at rest is right shifted compared to atrial and during exercise the shift is increased

Question 13

What are the 3 forms that CO2 is transported in through the blood

Answer 13

1. Dissolved in plasma and cytoplasm (7%)
2. Bound to Hb (Carbamion-CO2) (23%)
3. Bicarbonate - 70%

Question 14

How is CO2 carried through the blood by bicarbonate

Answer 14

• Carbonic anhydrase is the second most abundant protein in red blood cells
• Catalyzes the reaction CO2 + H2O = HCO3- + H+
• Bicarbonate is equilibrated between cytoplasm and plasma via HCO3-/Cl- exchanger

Question 15

Haldane Effect

Answer 15

Total CO2 content of blood depends on O2
- There is an interaction between the binding of O2 and of CO2/H+ on hemoglobin
- As PO2 decrease, it increase CO2 loading and decreases hemoglobin’s affinity for O2
- Leads to O2 unloading

Question 16

Direct effect of changes in PO2 on O2 loading

Answer 16

As PO2 increases O2 loading increases and vice versa

Question 17

Effects of change in PCO2

Answer 17

Increased PCO2 causes increased CO2 loading and increase in H+ ions