lecture 12 Flashcards
(17 cards)
the oxygen cascade
- gas exchange occurs at the lungs & the muscles
- lungs and muscles are connected through circulation
gas exchange in body
- differences in partial pressure are responsible for the exchange of O2 and CO2 that occurs (via diffusion) between:
1. alveoli and pulmonary capillaries
- alveolar-arteral interface
2. tissues ad tissue capillaries
- arterial-myocyte interface
the gas partial pressure gradient detmines how they flow:
- O2 partial pressure has to be highest in atomsphere & lowest in muscle
- if we want CO2 to be blown out = highest in muscle & lowest in alveoli
- look at diagram
external gas exchange
- O2 diffuses into arterial ends of pulmonary capillaries and CO2 diffuses into the alveoli because of differences in partial pressure
- as a result of diffusion at the venous ends of the pulmonary capillaries, the PO2 in blood is equal to the PO2 in the alveoli and the PCO2 in blood equals PCO2 in alveoli
- PO2 in blood in pulmonary veins is less than in pulmonary capillaries de to Va-Q mismatch
- O2 is lower when it gets closer to left side of heart
- PO2 = 104 (pulmonary cappillaries)
- PO2 = 95 (pulmonary veins) - shunt lowers PO2 slightly but does not really have any other effect
- some people might have alveoli who’s partial pressures are nt in this range
- may not exchange gas in an efficient way
- low O2, high CO2 in alveoli
- less opportunity for diffusion to occur - key takeaway:
- most of the blood rapidy establishes an equilibrium
- except for PO2 in pulmonary capillary due to the 2 reasons listed aboe
inernal gas exchange
- O2 diffuses out of arterial ends of tissue capillaries and CO2 diffuses out of of tissue because of differences in partial pressure
- as a result of diffusion at the venous ends of tissue capillaries, the PO2 in blood is equal to the PO2 in the tissue and the PCO2 in blood equals PCO2 in tissue
- blood becomes oxygenated at the lungs
- pumped to systemic circulation, where i can go anywhere
- focus is on how to get blood to skeletal tissue
- low O2 blood becomes oxygenated
- high CO2 blood gets rid of the CO2
** blood exchange is all driven by partial pressure gradients
oxygen transport cascade
gas partial pressures as O2 moves from ambient air at sea level to mitochondria of maximally active muscle tissue
PO2 is important because:
1. its gradient drives diffusion
2. impacts how O2 and CO2 are transported and delivered
159mmHg to 103mmHg
- tiny drop occurs from 103-95
- all of the gas diffusion occurs at the arterial level
- arterial circulation is high
- where PO2 exits the capillary (~40)
- PO2 in mitochondria (witin cell) is extremely low (~2-3mmHg)
- there is always a gradient for O2 to flow from blood to muscles
- but it is always very low level of mmHg in themitochondria
how is O2 transported in the blood?
- red blood cells (erythrocytes)
- no nucleus, unable to produce; replaced regularly via hematopoiesis (life span ~4 months)
- produced and destroyed at equal rates
- contain hemogobin
- volume typically stays aroundthe same - hemoglobin
- O2 - transporting protein in red blood cells (4 O2 per hemoglobin)
- heme (pigment, iron, O2) + globin (protein)
- 250 million hemoglobin per red blood cell
- co-operativity: O2 binding increases affinity for subsequent O2 binding
- 4 binding sites 4 oxygen (4x250) = 1,000 massive O2 carrying capacity - hemoglobin within red blood cells cell & sites in cell with iron present attract the O2 to them
- affinity = how strong the magnet is for O2
- 4 iron sites:
- when 1 O2 molecule bind, the other 3 O2 molecules develop a higher infinity for O2
- this occurs when the 2nd & 3rd bind as well
- more O2 on binding site = the higher the affinity for O2
blood components
55% plasma
90% H2O
7% plasma proteins
3% other
45% formed elements
>99% red bood cells
<1% white blood cells and platelets
hematocrit = 45% formed elements/100% total blood volume = 45%
skeletal musle of a hamster
- watched the red blood cells go through the tissue
- red blood cells go through capillaries connect & drain into veins
- arterial circulation deliveries them across capillary bed & sent to be drained in the heart
- this is the interface of gas exchange
40x
O2 transport: alveoli to blood
blood transports O2 in 2 ways:
1. dissolved in fluid portion of blood (establishes PO2) (2%)
- 2%
- some O2 molecules jut cross the interface & dissolve into blood plasma
- not bound to anything — just floating around
- established the partial pressure of O2 within the fluid
2. combind with hemoglobin (Hb) in red blood cells (98%)
- 98%
- attaches to hemoglobin
- forms oxygenated hemoglobin
pulmonary artery - PO2 = 40 —> to PO2 = 85, then —> to pulmonary vein at PO2 = 95
- focusing specifically on O2
- O2 transport from alveoli to blood
- short distance by which O2 has to diffuse
- red blood cell is coming from pulmonary artery & going back towads pulmonary vein
- into pulmonary circulation, PO2 = quite low — PO2 is much higher when it leaves (~95-103)
arterial-venous O2 difference (a-VO2diff)
a-VO2diff = CaO2 - CvO2
resting VO2
- CaO2 = [15g/100m x 1.34mLO2/g x 0.98] + [100mmHg x 0.003] = 20mL/100mL blood
- CvO2 - [15g/100mL x 1.34mLO2/g x 0.75] + [40mmHg x 0.003] = 15mL/100mL blood
- a-VO2diff = 5mL/100mL blood
VO2max
- CaO2 = 20mL/100mL blood
- CvO2 = [15g/100mL x 1.34mLO2/g x 0.25] + [35mmHg x 0.003] = 5mL/100mL blood
- a-VO2diff = 15mL/100mL blood
- important from exercise perspective = how much O2 is being taken up & used by the muscle
- O2 pressure is different between arterial & venous
- hemoglobin does not differ between arterial & venous
- arterial = oxygenated blood:
- 20mL = standard arterial O2 content - venous = deoxygenated blood:
- lower saturation
- less O2
- some O2 has been released from hemoglobin & goes into muscle
- PO2 is lower
- 15mL f O2 per 100mL of blood - 5 mL of 100mL of blood is extracted & taken into the tissue
- majority of O2 coming in is still in the blood unil we exercise
- the leftover O2 in blood can be used to supply O2 when exercising - VO2 max
- bigger reduction in pressure for the same delivery of blood????
a-VO2diff vs exercise intensity
CaO2 = [Hb} x 1.34 x SO2 + PaO2 x 0.003
CvO2 = [Hb] x 1.34 x SO2 + PaO2 x 0.003
mixed venous O2:
- all of tissues exercising & non-exercising mixed together
measured arterial content does not change in males & females
as exercise intensity increases..
- venous capacity decreases as
- we are extracting more O2 that’s arriving at tissue level
oxyhemoglobin dissociation cuve
- loading portion. the curve: saturation stays high even with large changes in PO2
- unloading portion of the curve: saturation changes quickly with even small changes in PO2, allowing oxygen unloading to tissues
think about it in both directions
- muscle to lung
- lung to muscle
- why does O2 release from hemoglobin?
- the dissolved O2 is important for this (PO2)
- even though it only represents 2% of the blood - % of O2 bound to hemoglobin depends on the PO2
- as PO2 falls & the dissolved O2 diffuses into any tissue is capillary that O2 bound to hemoglobin also falls???
- closer to 1:
- O2 saturation starts to fall
- the more PO2 falls - the more O2 we release from hemoglobin - leading phase = going up curve
- unloading phase = going down curve
- always changing because PO2 is a dynamic # (especially when it starts crossing capillaries)
CaO2 - PaO2 = 100mmHg (alveoli)
CvO2 - PvO2 = 40mmHg (resting tissue)
- in alveoli our mean pressure = ~100mmHg
- almost all of our O2 is bound to hemoglobin (high saturation of hemoglobin) - PO2 starts to gradually fall
- ~40mmHg at end of capillary - have enough information to calculate arterial & venous oxygen content
- when we exercise - what’s coming into the muscle does not change
- but O2 is being used at a higher rate
- causing more diffusion of O2 out of blood & into the muscle
alveoli CaO2 - PaCO2 = 100
exercising muscle CvO2 - PvO2 = 30
- when partial pressure in muscle falls…
- because of shape of curve
- the small change in PO2 gives us a massive difference in terms of O2 saturation
- when we get a low PO2 - O2 flies off of hemoglobin in blood, dissolving into muscle - 30s breath-hold
- as you hold your breathe - PO2 goes down in a linear fashion
- saturation will also go down
- begins ging down really slow but then starts to fall rapidly - PO2 starts to fall linearly
- but dissociation curve maintains saturation high until critical level where PO2 starts to fall
oxyhemoglobin dissociation curve shifting
curve is dynamic in terms of:
- where it is in the body
- position of signoidal relationship in different positions
left shift
- decreases ability to unload O2 (i.e. increase affinity)
- increase pH (alkalosis)
- decrease PCO2
- decrease temp
- decrease 2,3-diphosphoglycerate
- done in environmental conditions when we want to conserve oxygen
- important when hypothermia
right shift (bohr shift)
- increase ability to unload O2 (i.e. decrease affinity)
- decrease pH (acidosis)
- increase PCO2
- increase temp
- increase 2,3-diphosphoglycerate
- particularly relevant with exercise:
- increase metabolic heat and acidity in active tissues = increase O2 release
- important for exercise
- exercises curve to shift to the right - allows more extraction of O2
evidence of “Bohr Shift” during severe-intensity exercise
in areas where CO2 or [H+] is high (e.g. active muscle), O2 is less tightly bound with hemoglobin and O2 is released more readily (the bohr effect)
- evidence of the bohr effect:
- group of participants performing severe intensity exercise (above CP) & heavy intensiy exercise (below CP) - measured mean hemoglobin saturation, and muscle pH
- one is more acidotic than the other
- one has a drastic fall where the other falls gradually over time
- these graphs have the same PO2:
- higher intensity exercise = more offloading of exercise than the lower levels of exercise
- more offloading of O2 for the same amount of PO2
CO2 transport: muscle to blood
blood transports CO2 in 3 ways:
1. dissolved in fluid portion of blood (establishes PCO2) (10%)
2. combined with hemoglobin (Hb) in red blood cells (20%)
3. combined with water as bicarbonate (70%)
artery - PCO2 = 40, to vein PCO2 = 46
- starting at the muscle
- muscle is producing CO2
- partial pressure of CO2 is high in muscle & lower in bood - CO2 is transport in the blood in 3 different ways:
1) establishes PCO2
2) CO2 can also be carried by hemoglobin (CO2 is carried away from tissues bound to hemoglobin)
3) CO2 diffusing into blood plasma by diffusing to water
- produces bicarbonate & hydrogen ions - PCO2 rises as it flows past the tissues
CO2 transport: blood to alveoli
oxygen pikup and carbon dioxide release in the lungs
pulmonary artery - PCO2 = 46, then to pulmonary vein = 40
- CO2 = the opposite of oxygen
- CO2 is lower in alveoli than in the circulation
- CO2 goes in
- hemoglobin release CO2 & CO2 goes into alveoli
- poduces water & H2O
- CO2 is removed from the blood
- lower level of PCO2 arriving back at the left side of the heart
CO2 dissociation curve and the Haldane effect
- binding of O2 with hemogloin tends to displace Co2 from the blood
- this effect, called the Haldane effect, promotes CO2 transport
- pressure in blood
- CO2 bound to hemoglobin (or present as bicarbonate)
- exponential type of relationship
- our body can tolerate a large amount of PiO2
- but our bodies are intolerant to large amounts of PCO2 due to carbonic anhydrase reaction
- CO2 acumulation is associated with acidosis & our body does not want to affect pH
- need to regulate PCO2 in a very narrow window - average operating range for PCO2 = ~40-50mmHg
haldane effect:
- when O2 binds with hemoglobn (lung), CO2 is released
- when O2 offloads from hemoglobin (tissue), CO2 binds to increase CO2 transport
- more of a linear relationship
- as PCO2 falls - release more CO2 off of hemoglobin & it is put into alveoli
- at tissue, the opposite happens
- go from a low to a high
- we pick up more CO2 - as we reduce the pressure of CO2 - we release & offload CO2
- as we reduce CO2 from tissue
- the CO2 relationship depends on oxygen
- can cause it to shift up and down
- when O2 is high (at the lungs)
- we are more predisposed to getting PCO2
- when O2 is low (at the muscle)
- we are more predisposed to piking up PCO2
