Respiratory Gas Exchange

Question 1

What are the units of gas pressure?

Answer 1

1 atmosphere = 760 mmHg = 101 kPa

so 1 kPa = 7.5 mmHg

Question 2

Describe Dalton’s Law

Answer 2

gases in a mixture exert pressures that are independent of each other

Question 3

Equation of Dalton’s Law

Answer 3

Atmospheric pressure is therefore the sum of the partial pressures of all the gases in the atmosphere:
Patmos = PN2 + PO2 + PCO2 + PH2O + Pothers

Question 4

Describe Henry’s Law

Answer 4

the concentration of a dissolved gas is directly proportional to its partial pressure

Question 5

Equation of Henry’s Law

Answer 5

Csoln = kH x Pgas

Question 6

What is the equation of passive diffusion through biological membranes?

Answer 6

P= DKa/d
Permeation rate= P(Cout- Cin)
D= diffusion constant(rate at which diffuses once dissolved)
K= partition coefficient (tendency to dissolve)
d= membrane thickness
a= membrane area

Question 7

How does diffusion differ between CO2 and oxygen?

Answer 7

CO2 x20 than oxygen once dissolved- more likely in equilibrium

Question 8

How much oxygen is there in the blood and where is it?

Answer 8

PO2 = 13.3 kPa
[O2] = 200 ml/L = 8.9 mmol/L
Of this, 1.5% is dissolved in plasma (3 ml/L, 0.13 mmol/L)
98.5% is bound to haemoglobin (197 ml/L, 8.77 mmol/L)

Question 9

Describe the structure of a single subunit of haemoglobin

Answer 9

Ferrous iron occupies the centre of the porphyrin ring and establishes linkages with all the four nitrogen of all the pyrrole rings.
It is also linked to the nitrogen of the imidazole ring of histidine present in the globin part.

Question 10

Describe the quaternary structure of adult haemoglobin

Answer 10

4 subunits
Alpha 1, 2 and Beta 1, 2
tetrameric protein with two types of subunit, and molecular weight 64,500

Question 11

How is myoglobin different to haemoglobin?

Answer 11

One subunit, one haem group

Found in muscles

Question 12

What shape is the oxygen saturation curve of haemoglobin and why?

Answer 12

Sigmoid
Each molecule of Hb binds 4 molecules of O2, with no change in the oxidation state of the iron (Fe2+).
O2 binding to one subunit causes a protein conformational change, which is transmitted to the other subunits by non-covalent inter-subunit interactions; this results in an increase in the oxygen-affinity of the unoccupied subunits, hence cooperativity in oxygen binding.

Question 13

What is cooperative binding?

Answer 13

Changes spin state of iron, conformational change transmitted to other subunits

Question 14

How would lower pH affect the saturation curve?

Answer 14

High H+ conc, lactic acid formation, more dissociation

Question 15

What is the equation for the Bohr effect?

Answer 15

Hb-NH2.O2 + H+ = Hb-NH3+ + O2

Question 16

What is the Haldane effect?

Answer 16

increase CO2 also displace oxygen from haemoglobin (temp) deoxygenates oxyhaemoglobin

Question 17

What is the equation for the Haldane effect?

Answer 17

Hb-NH2.O2 + CO2 = Hb-NH-COO- + H+ + O2

Question 18

What is the equation for binding of 2,3-bisphosphoglycerate?

Answer 18

Hb.O2  +  BPG = Hb-BPG  +  O2
metabolite present in erythrocytes at a concentration similar to that of [Hb] (~2 mmol/L), binds preferentially to deoxy-Hb, favouring oxygen release, i.e. it lowers the oxygen affinity. 
Foetal Hb (HbF) has a lower affinity for 2,3-BPG so a higher oxygen affinity than HbA

Question 19

How is nitrogen gas used dissolved in the body?

Answer 19

Elemental nitrogen (N2) has no function in human metabolism. Its solubility in blood is low, but at high pressure it dissolves in blood and tissues, producing nitrogen narcosis (‘rapture of the deep’); on return to normal pressure nitrogen emboli may form in capillaries, causing local ischaemia, and painful bubbles develop within tissues (‘bends’).

Question 20

Why is there only two conformational states of the Hb tetramer?

Answer 20

(‘oxy’ and ‘deoxy’) and in each state the subunits are symmetrically arranged and in the same conformation. This cooperative binding of oxygen actually reduces the affinity of Hb for oxygen, compared to that of its individual subunits (c.f. myoglobin), and ensures that binding and release of O2 occurs over a relatively small range of oxygen concentrations:

Question 21

Why is carbon monoxide a problem?

Answer 21

Carbon monoxide binds to Hb with 200-250-fold higher affinity than oxygen. CO poisoning is very serious because in Hb-CO (i.e. with CO bound to a single haem) the O2 affinity of the remaining sites is increased - O2 is therefore released only poorly, affecting oxygen delivery to tissues.

Question 22

What is methaemoglobin?

Answer 22

Oxidation of the iron in haemoglobin to Fe3+ converts it to methaemoglobin (metHb), which does not bind oxygen. In erythrocytes, methaemoglobin reductase reduces metHb back to Hb.
Normally only about 1% of haemoglobin is present as metHb, but some mutations in haemoglobin genes (HbM) stabilize the oxidized state, resulting in higher levels of metHb (methaemoglobinaemia); this can also result from mutations in the repair systems.

Question 23

How does CO2 interact with haemoglobin?

Answer 23

The solubility of CO2 in water is much higher than that of O2; it is also hydrated to carbonic acid, and it can combine directly with haemoglobin. (It does not bind to the haems, but reacts with the N-terminal amino-groups.) As noted above, deoxygenation of oxy-Hb promotes binding of CO2 to deoxy-Hb, and vice versa (the Haldane effect).

Question 24

What is CO2 converted into?

Answer 24

In erythrocytes carbonic anhydrase catalyses hydration of CO2 to carbonic acid (pKa = 3.5), which ionizes to bicarbonate: further ionization of bicarbonate to carbonate (CO32–) is negligible in blood, as the pKa is so high (pKa = 9.8).

Question 25

Why is CO2 converted into bicarbonate?

Answer 25

Bicarbonate moves into the plasma, in exchange for Cl– - the ‘chloride shift’ – so most CO2 is transported is as bicarbonate in plasma (rather than bound to haemoglobin within erythrocytes).

Question 26

What is Acetazolamide?

Answer 26

Acetazolamide (diamox), an inhibitor of carbonic anhydrase, was once used as a diuretic, because it inhibits the reuptake of Na+ and bicarbonate in the kidney. Nowadays its widest use is in preventing altitude sickness, by slightly lowering the pH of blood, which stimulates respiration and the release of O2 from oxyhaemoglobin.

Question 27

What is the pathway from oxyhaemoglobin to oxygen?

Answer 27

Met-Hb and O2- superoxide
Superoxide converted into hydrogen peroxide (H2O2) by superoxide dismutase
Converted into oxygen by catalase