Intro

Question 1

Respiratory system

Answer 1

Body part and anatomical designs that enable us to move air and exchange vital gases

Question 2

In equilibrium gases move down pressure gradient

Answer 2

There is no active pump to get oxygen into the blood
 Similarly, no pump to get CO2 out of the blood
Movement occurs by diffusion

Question 3

Partial pressure

Answer 3

Pressure a single component gas would exert if it were removed from the gas mixture and placed in an equivalent volume

Question 4

Law of partial pressure (Dalton’s law)

Answer 4

total pressure in a system is the sum total of all the partial pressures of the (non-reacting) gases

Question 5

Atmospheric pressure

Answer 5

“Room air” = air exposed to atmosphere pressure (Patm)

Patm also called barometric pressure

Question 6

Inspired air, dry

Answer 6

160 mmHg

Question 7

Inspired air, saturated with water vapour

Answer 7

150 mmHg

Question 8

Alveolar gas

Answer 8

100 mmHg

Question 9

Arterial blood

Answer 9

95 mmHg

Question 10

Tissues, interstitium

Answer 10

40 mmHg

Question 11

Mitochondria

Answer 11

4-10 mmHg

Question 12

Alveolar gas equation

Answer 12

PAO2 = [(Patm – PH20) x FiO2] – (PaCO2/RQ)

Question 13

Respiratory quotient

Answer 13

Ratio of molecules of CO2 produced for molecules of )2 consumed

Question 14

Oxygen carriage in blood

• solubility
• dissolved O2 content

Answer 14

Oxygen is very soluble

Dissolved O2 content = 0.003 mLO2/dl/mmHg x PO2

So even with a PaO2 ~100 mmHg, the amount of oxygen dissolved in blood is small (~15 mL/min in entire blood pool)

Oxygen consumption(VO2) of the body, AT REST, is around 250 mL / min

Question 15

Henry’s Law

Answer 15

A gas dissolves in a liquid in direct proportion to its partial pressure and solubility.

Question 16

Haemoglobin O2 saturation

Answer 16

Hemoglobin subunits can be in a T (taut) or R (relaxed) state. T state subunits are NOT able to bind O2. R state hemoglobin are able to bind O2.

Saturated (oxy-Hb)

Range: 0-100%

Question 17

Haemoglobin saturation measurement

Answer 17

A probe is placed on the finger, toe, ear lobe or nose. Two light-emitting diodes produce beams at red and infrared frequencies (660 nm and 940 nm, respectively). There is a photo detector on the other side. The diodes flash at approximately 30 times per second. The diodes are switched on in sequence, with a pause with both diodes off. This allows compensation for ambient light. The microprocessor analyses the changesin light absorption during the arterial pulsatile flow and ignores the non-pulsatile component of the signal (which results from the tissues and venous blood).

Question 18

Oxygen content of blood

Answer 18

Two forms of oxygen carriage in the blood - dissolved and Hg-O2 - make up the O2 content of (arterial) blood (CaO2). Most of the O2 content is Hg bound.

CaO2 (ml/dL) = [PaO2 x 0.003 ml/dL] + [1.34* ml O2/g Hg x Hg (g/dL) x SaO2]
CaO2 (ml/dL) = [100 x 0.003 ml/dL] + [1.34 ml/g x 15 g/dL x 1]
CaO2 (ml/dL) = 0.3 + 20 mL/dL = 23 ml/dL
CaO2 (ml/L) = 3 + 200 = 203 mL of O2 /L of blood

With average circulating blood volume of 5 L / min, the delivery of oxygen (DO2) is ~ 1000 mL/ min. This meets our metabolic needs (resting VO2 ~ 250 mL / min).

Question 19

Reduced O2 delivery

Answer 19

Reduced content
Hypoxemia (ie reduced PaO2)
Anaemia
Interruptions to Hg binding

Insufficient cardiac output

Question 20

Haemoglobin

Answer 20

Hg-oxygen binding demonstrates property of cooperative binding

This is due to allosteric effects (conformational change effect) of tetramer configuration

Question 21

Hb-O2 binding

Answer 21

Hg loads and then unloads oxygen

Determinants of O2 binding:
Saturation properties: PO2 drives O2 saturation

Cooperative binding (among 4 Hg subunits)

Other factors have allosteric effects and alter the affinity for oxygen

Question 22

Oxygen dissociation curve

Answer 22

Depicts the relationship between PaO2 and SO2

Sometimes display content of oxygen (Cao2) instead of SaO2 on the y-axis

Question 23

Allosteric effectors

Answer 23

homo-tropic allosteric effect: the ligands are the same. The binding of O2 on one Hg subunit effects (increases) the binding of other O2 molecules to the remaining 3 subunits. This fosters the LOADING OF OXYGEN.

hetero-tropic allosteric effect: different ligands. For example the binding of CO2, H+, or 2,3 DPG to non-heme portions of the hemoglobin effects (reduces) the binding of O2 molecules to heme

H+, CO2, and 2,3 DBP stabilize the T state, fostering the RELEASE OF OXYGEN

Question 24

Hb-O2 affinity altering factors

Answer 24

By favouring the T state, pH and 2,3 DPG alter the affinity of Hg for O2.

Temperature (non-allosteric influence on affinity) has the same effect.

These factors “shift the curve” to the right or the left.

Question 25

P50 definition

Answer 25

The P50 (PaO2 at 50% saturation) as an index of the affinity of Hg and O2.

Question 26

Foetal Hb

Answer 26

Foetal Hg (α2γ2) is unable to bind 2,3 DPG (which stabilizes the T state).

Thus the R state is favoured, which fosters oxygen loading.

Shift to left

Question 27

Why does CO bind to Hb

Answer 27

CO is colourless, odourless and tasteless. Can be difficult to know when CO exposure is occurring.

Forms carboxyhaemoglobin (CO-Hb), > 200 times affinity for Hb compared to O2

Question 28

Effects of CO on Hb

Answer 28

CO impairs both loading and unloading of O2:
O2 content is reduced due to CO outcompeting O2 for Hg binding
CO stabilizing the R state (ie left shift) for the remaining sites. This impedes release of O2.

PaO2 of blood may be normal in CO poisoning

Symptoms: headache, nausea/vomiting, dizziness/lethargy/weakness  confusion  coma and death (when CO-Hg > 40%)

Question 29

Cyanosis

Answer 29

Blue-ish discoloration of skin evident in conditions of hypoxemia (low blood oxygen)

Requires a critical threshold of deoxygenated Hg

Typically correlated to a saturation < 80%

Question 30

Bicarbonate

Answer 30

HCO3- is formed through the hydration of CO2 and subsequent dissociation of carbonic acid
CA
CO2 + H2O H2CO3 H+ + HCO3-

RBCs contain carbonic anhydrase (CA) which catalyses 1st step
2nd step happens spontaneously
HCO3- ions readily diffuse out from the RBC into the plasma
H+ ions cannot, and are buffered by Hb:
H+ + Hb.O2 H+.Hb + O2
DeoxyHb is a better proton acceptor than OxyHb (O2 unloading H+ loading)
Plasma Cl- ions diffuse into the RBC to maintain electro-neutrality (chloride shift)

Question 31

Transport of CO2

Answer 31

Carbon dioxide transport in the blood: soluble gas (5%), carbamino compounds (5%) and bicarbonate(90%).

Question 32

CO2 elimination

Answer 32

Easy diffusion due to high solubility constant

PvCO2 45 mmHg PACO2 40 mmHg

Question 33

How can we verify CO2 elimination

Answer 33

If the PACO2 is 40 mmHg, what would the PaCO2 be?

The brain maintains pH and PCO2 homeostasis; when PaCO2 rises > 40 mmHg (respiratory acidosis – lecture 3 alert!) the brain triggers increased ventilation.