Week 20: (B) O2 & CO2 Transfer Between Alveolus, Blood & Tissue. Flashcards
What does Fick’s law refer to?
Gas exchange across the Blood-Gas barrier in the Alveolus occurs by diffusion
What is the Fick’s Law equation?
Dt=KtS(1/T)
What does Dt refer to?
Rate of Oxygen Transfer to
Hemoglobin (mlO2.cm-2.min-1)
What does Kt refer to?
Rate at which oxygen travels through liquid
“Krogh’s Oxygen Permeation Coefficient”
(3.3x10-8 cm-2.min-1.mmHg-1)
What does S refer to?
Surface Area (cm2)
What does (1/T) refer to?
Mean Barrier
Thickness (10-4cm)
Why are the capillaries thin?
Needed for optimal O2 transfer to haemo
What are the 2 forms of oxygen transport?
physical- Plasma soluble O2 (2%)
chemical- O2 bound to Haemoglobin (98%)
What are features of Plasma soluble O2?
-Less Soluble than CO2
-Function of Partial Pressure of O2 in alveolus
-0.3ml O2/100ml blood at PO2 of 100mmHg
(= normoxic alveolar PO2 )
What are features of O2 bound to haemoglobin?
-Rapid and reversible interaction
-Reversibility enables O2 off-loading to tissues
Hb + O2 ↔ HbO2
What is deoxyhaemoglobin?
form of haemoglobin without O2
What is Oxyhaemoglobin?
The form of haemoglobin bound to O2
What is the O2 carrying capacity of Hb?
1.34 x 15 = 20mls O2/ 100ml
1g Hb binds 1.34ml O2
15gHb/100ml total blood
What is the total arterial blood O2 content? (CaO2)
20.3mlsO2/100ml total blood
What is the total venous blood oxygen content? (CvO2)
15.28mlsO2/100ml total blood
What is the tissue O2 uptake?
5mlsO2/100mls
total blood
What is the difference between oxygen content and saturation?
- Content (CaO2 or CvO2): -Determined by amount of Hb and O2 in blood
- Saturation (usually SaO2): Proportion (%)
What is the Oxygen saturation equation?
oxyhaemoglobin/ O2 Carrying Capacity of Hb
What happens to saturation if O2 content differs?
saturation can remain the same
Hb content can differ but saturation is a percentage so it is all proportional
What is polycythaemia and anaemia?
Polycythaemia is high Hb content, carrying capacity and oxyhaemoglobin
Anaemia is Low
What defines the total oxygen content of blood?
Hb O2 Carrying Capacity and HbO2
deoxyhaemoglobin + oxyhaemoglobin
On the oxyhaemoglobin dissociation curve what does the EC50 tell us?
gives PO2 (mmHg) required for half max Hb saturation
What pressure does the venous blood enter the alveolus?
40 mmHg (75% sat)
What pressure does alveolar pressure equilibrate to?
100 mm Hg (97% sat)
How does the oxyhaemoglobin dissociation curve show that the arteries have a higher affinity for O2?
As its box lies on the arterial plateau phase
ensures maximal O2 saturation even if there is a considerable drop in PO2 (mmHg)
To decrease Hb saturation, would have to decrease pp considerably
How does the oxyhaemoglobin dissociation curve show that the arteries have a lower veins for O2?
Box lies on the steep part of the curve
haem needs to dissociate O2 so O2 leaves haem and diffuses into tissue.
If we deoxygenate blood in the venous system by ~10 mmHg, Hb sat would decrease far greater than arterial
FAVOURS OFF-LOAD
greater oxygen dissociation for small changes in tissue PO2(partial pressure)
What causes the off-load of O2 to the tissue?
If the Partial pressure in a tissue is low it causes the Veins to off-load oxygen, decreasing Hb saturation in blood
What is the normal P50 in the alveolus?
27mmHg at Ph7.4 and PCO2 of 40mmHg
What does a left-shift in the Oxyhaemoglobin Dissociation Curve mean?
Increased Hb-O2 affinity and reduced O2 offloading to tissues (eg Fetal Hb)
What does a right-shift in the Oxyhaemoglobin Dissociation Curve mean?
Decreased Hb-O2 affinity and raised O2 offloading to tissues (eg High Altitude)
What are factor that make the dissociation curve shift to the right?
Stressors such as... acidosis pH increased PCO2 fever, increase core temp hypoxia glycolysis (increase 2,3 Bisphosphoglycerate) (2,3BPG)
What 2 factors are the Bohr effect?
acidosis pH
increased PCO2
What 2 factors alter Hb binding affinity?
pCO2 and pH alter Hemoglobin-O2 Binding Affinity
Describe the structure of Hb? AND how its affinity is altered?
-Oxygen reversibly binds to Fe3+ ions in the centre
of the heme ring
-Contains 4 iron-binding HEME domains
-Heterotetramer composed of 2alpha and 2betasubunits (differ in foetal)
-CO2, pH and 2,3 BPG alter this affinity by interacting
with charged amino groups between the a and b subunits
How does pH alter the ability of O2 to bind to Hb?
Amino terminus of the hemoglobin alpha subunit binds to the carboxy-terminal histidine in b subunit – this stabilises Hb structure.
This interaction is pH and O2 sensitive – requires 1 H+ for each 2O2 released (de-oxy Hb)
In Acidosis, decreased pH (=↑[H+]) favours the a-b subunit interaction and reduces the binding of O2 to heme.
H+ stabilises alpha beta Hb subunit interaction
How does CO2 reduce Haem affinity?
CO2 alters blood pH and reduces haemoglobin affinity for oxygen
What 2 ways does increased blood pCO2 releases O2 from Hb?
1) Production of Carbonic Acid in Red Cell CO2 + H2O → H2 CO3 ↔ HCO3- + H+ 2) Carbamate Reaction at N-terminal Amino Groups on Hb a-subunit CO2 + R-NH2 ↔ R-NH-COO- + H+
What enzyme is used in the production of Carbonic Acid and carbonate ion?
Carbonic Anhydrase
What are the 3 forms CO2 is transported in?
Soluble CO2 gas (5%)-physical
Bicarbonate Ion (90%)-physical
Carbamate reaction at N-terminal amino groups of Hb a subunit (5%)- chemical
What are the 2 categories which CO2 can be transported?
Physical - Plasma soluble Co2
Chemical - Carbamino Haemoglobin R-NH-COO-
Is CO2 or O2 more soluble in plasma?
Co2 20 times more soluble
How is Co2 removed from the RBC to maintain a gradient?
Exchange of HCO3- (out) for Cl- (in) maintains gradient for CO2 uptake into red cell and buffers pH of blood plasma to ~ 7.4. As Cl- increases, Cl in and HCO3 out
What are the physiological effects which alter blood carriage of CO2?
Haldane effect
deoxygenation of blood improves carriage of CO2
Altered by tissue oxygenation
Hypoxia has highest CO2 content (ml/100ml blood)
What is the Haldane effect?
Low tissue O2 favours CO2 carriage by blood
relationship between CO2 carriage and O2 carriage in blood
What is the Bohr Effect?
-Carbamate reaction reduces HbO2 affinity
-Increased red cell [H+] reduces
HbO2 affinity by promoting ab Hb subunit interaction
What does oxygen equilibrate with?
alveolus to blood
What does CO2 equilibrate with?
blood to alveolus
What does the CO2 and O2 equilibrates help us to understand? of O2 and CO2 i
O2 and CO2
partial pressures in the alveolus and arterial blood can be used to understand how lung ventilations matched with blood perfusion of the lung.
How is the ventilation and perfusion relationship of O2 and CO2 adaptable?
1) Changes in breathing and lung perfusion allow fine-tuning of O2
uptake and CO2
clearance from one environment to another (eg high altitude
mountaineering),
2) Tolerance of G-force (space flight) and
3) External pressure (diving))
What is the relationship between PO2 and PCO2?
Alveolar PO2
varies with Arterial PCO2
What happens to the partial pressure gradient at the summit of Everest?
The PIO2 (inspired oxygen) is 40mmHg which is near the venous PO2 at sea level (43 mmHg) so loss of partial pressure gradient -PATM 252 mmHg and pAO2 is 34.2 (less than venous PO2 at sea level) oxygen can leave body
Why does arterial paCO2 decrease at the summit ofEverest?
breathing rate increases, blow out CO2 arterial P decreases
How do we conserve pACO2? (high altitude adaptation)
1) Increasing Breathing Frequency (F) ->paCO2 decreases
2) High Carbohydrate Diet (Eat Pasta) –> RQ =1
3) Climb when barometric pressure high (see also Krogh Permeation Coefficient
What does the low PAO2 tell us from the equation?
• The equation tells us that alveolar PO2 is significantly affected by atmospheric PO2 and arterial carbon dioxide.
• If arterial PCO2 (paCO2) increases so alveolar PO2 decreases (Hb oxygenation also
affected – see Bohr and Haldane effects)
• If RQ increases (eg carbohydrate diet, RQ=1) alveolar PO2 increases.
What is the lungs adaptation to poor ventilation and large blood flow? low O2
- Need to reduce perfusion - hypoxia constricts pulmonary arterioles. -Hypoxia – constricts pulmonary arteries to increase pulmonary transit time of blood (Q). -Re-directs blood flow to well ventilated areas of lung
What is the lungs adaptation to good ventilation and poor blood flow? high O2
-Need to reduce ventilation
- Low CO2 constricts bronchioles constricts bronchioles to area of vascular obstruction.
- Re-directs air flow in lungs away from
obstruction
What is perfusion and ventilation in the lungs?
Ventilation (V) refers to the flow of air into and out of the alveoli, while perfusion (Q) refers to the flow of blood to alveolar capillaries.
What is the relationship between ventilation and perfusion?
Va/Q
