lecture 17 Flashcards
(17 cards)
O2 utilization in mitochondria
O2 drives the flow of electrons along the electron transport chain which facilitates proton pumping and establishes the electrochemical gradient necessary to drive ATP synthase:
1. O2 is drawn from complex 4 where it accepts electron pairs
2. the reduced form of O2 then combines with a pair of electrons to form H2O
flow of O2
blood plasma —> capillary endothelium —> interstitial space —> sacroplasm —> mitochondria —> complex 4
white arrows show pathway of O2 from RBC in the capillary into the myocyte and toward the mitochondria
how do we deliver O2?
- convection —> transfer of O2 by movement of RBC within arterial blood to the tissue
- diffusion —> transfer of O2 from an area of high pressure (arterial blood) to low pressure (tissue)
- within the lung, O2 diffuses from alveoli into the pulmonary capillaries
- driven by the gradient between the partial pressure of O2 in the alveolar space and that in the deoxygenated pulmonary capillary blood
- within the tissues, O2 diffuses from the systemic capilaries into the skeletal muscle mitochondria
- driven by the gradient between the partial pressure of O2 in muscle capillaries and that of the mitochondria
matching systemic O2 supply with O2 demand (VO2)
convection
- VO2 = Q x a-VO2diff (frick principle)
(O2 uptake) = (flow of O2 rich blood) x (O2 extraction)
diffusion
- VO2 = Dmo2 x (PO2 capillary - PO2 mitochondria)
(O2 uptake)mL/min = (O2 diffusion capacity for skeletal muscle) mLO2/min x mmHg x (driving pressure for O2 into mitochondria) mmHg
Convective vs Diffusive O2 delivery
diffusive O2 delivery is a two-step process:
- diffusion of O2 from blood to sarcoplasm (cytosol)
- diffusion of O2 from sarcopasm to mitochondri
diffusion: VO2 = Dm [Pcapo2 - Pmito2]
convection: VO2 = Q [Cao2 - Cvo2]
partial pressure and HbO2
- when oxygented blood reaches muscle cells, the bond between O2 and Hb molecules weakens
- as RBCs pass single file through the tiny capillaries that surround muscle cells, O2 is released from Hb where it can then diffuse into the muscle cells
- this occurs because of the relationship between Hb affinity for O2 and blood PO2
why is the fall in PO2 at the tissues fortuitous?
why does arterial PO2 fall by so much once it centers the capillary?
why is mixed venous Po2 (20mmHg) lower than mean capillary PO2 (40mmHg)?
PaO2 / CaO2 — alveoli
PvO2 / CvO2 — exercising muscle
“mean capillary” PO2is used as an estimate of “driving pressure”
PO2 of arterioles, capillaries and veins
- as a plug of blood first enters the capillary, disolved O2 diffuses out of plasma, lowering its PO2
- this lowering of capilary PO2 facilitates off-loading of O2 from Hb in RBCs
- the further along the capillary (nearer to the venule), more and more O2 leaves the plasma causing an exponential-like fall in capillary PO2 (at 90)
- during exercise, particularly at high intensities, more and more CO2 is released from the tissue which increases capillary PCO2 towards the venular end
- facilitates further off-loading from Hb due to a rightward (bohr) shift in HbO2 dissociation curve (i.e. reduced Hb afinity for O2 at same PO2) - therefore, “end-capillary” PO2 may be quite low reltive to “mean capillary”
- the “driving pressure” for diffusion, therefore, is reduced progessively from the arterial to veous end of the capillary
90 - 20 but mean is ~40
- more oxygen being released
PCO2 does the opposite
O2 diffusion into mitochondria
- dissolved O2
- Myoglobin-facilitated O2 diffusion
O2 diffusion from blood to sarcoplasm
Myoglobin:
- an iron containing globular protein in skeletal and cardiac muscle fibers
- provides an “extra” O2 store to release O2 at low PO2
- resembls Hb because it also combines reversibly wih O2
- differs from Hb because each Mb molecule contains only 1 iron atom compared to 4 —>can only accept 1 O2, where Hb can accept 4
- in capillaries, Hb can hand off O2 to a Mb inside the muscle cell in the following chemical reaction:
- Mb + O2 —> MbO2
myoglobin
- the dissociation curve for Mb is different from Hb (i.e. much more readily binds and retains O2 at low PO2):
- at the low end of PO2 values, the curve abruptly increases in percentage b saturation with a erlatively small increase in PO2 unil the asumptote
- litte further change in saturation occurs over a broad PO2 range
- Mb affinity for O2 is not dependent on other variables (i.e. no crve shifting)
Hb: P50 = 37.0mmHg, n = 2.7
Mb: P50 = 5.3mmHg (80% is around where it plateaus)
factors affecting diffusive O2 delivery
- ability of muscle to extract O2 from blood t msucle mitochondria
muscle diffusion capacity
1. pressure gradient b/w capillary and mitochondria
2. contact area b/w RBC and myocyte
3. distance between capillary and mitochondria
fick’s Law of diffusion
muscle diffusion capacity
- pressure gradient b/w capillary and mitochondria (“P1 - P2”)
- contact area b/w RBC and mycyte (“area”)
- biggest square increase diffusion
- smallest square decrease diffusion - distance between capillary and mitochondria (“thickness”)
any condition that alters any of these variables will affect diffusive O2 delivery
effect of driving pressure on VO2max
VO2max is 25% less in hypoxia
decrease P = decrease diffusive delivery = decrease VO2max
*Mb - associated PO2 = cytosolic PO2
- decrease driving pressure = decrease VO2max
- 12% O2
- 16% O2
- 21% O2 - training increase dffusion capacity (Dmo2) such that a greater VO2max can be achieved for the same P
slope = O2 diffusion capacity for skeletal muscle mL O2 per (min x mmHg)
with training increase in VO2max (increase VO2 post training)
VO2 = Dmo2 x (PO2cap - PO2mito)
RBC spacing
- during exercise, greater convective blood dlow increases number of blood cells in a given capillary (less RBC spacing)
- increase hematocrit = increase functional surface area for diffusion = increase diffusive O2 delivery
- hematocrit = ratio of volume of RBC to total blood volume
RBC hemodynamics at onset of electrically stimulated rhythmic contraction of rat spinotrapezius muscle
capillarization
- increase capillaries in contact with muscle fibers (functional capillary surface areaa and decrease diffusion distance)
- ex. aerobic exercise training increases capillary-to-muscle fiber ratio
well trained - pre-exercise 1.5, post-exercise 1.6
untrained - pre-exercies 1.1, pot-exercise 1.1
diffusive O2 delivery during exercise
- when oxygenated blood reaches muscle capillaries, the bond between O2 and Hb molecules weakens
- as RBCs pass single file through the tiny capillaries that surround muscle cells, O2 is released from Hb
- Capillary PO2 > cytosolic PO2 so O2 diffuses into the sarcoplasm
- once inside the sarcoplasm, O2 can either diffuse directly into mitochondria or bind to myoglobin
- myoglobin shuttes O2 from cytosol to the mitochondria when cytsolic PO2 falls to critical levels during exercise
- once in he mitochondria, O2 is drawn to cytochrome c oxidase (complex 4) when it accepts electrons delivered by oxidation of CHO or FAT
- reduced O2 then picks uptwo H+ from the surrounding medium to form water
