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MINI TWO: Week 9 Lecture 18: Gas Transport in the Blood

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Oxygen is carried in two ways in the blood:
1. dissolved
2. bound to Hb
hemoglobin molecule
consists of four subunits each composed of a heme (porphyrin ring containing Fe+2) and a globin.

There are alpha and beta globins
So a complete Hb molecule consists of...
4 Hemes, two alpha globins and two beta globins
What can each HEME bind?
bind one oxygen so a fully saturated Hb molecules binds four oxygens
The total amount of Hb in the blood
15 g/100 mL of blood (15g/dL)
The amount of O2 in dissolved and bound forms is directly related to what?
to the PaO2 - as PaO2 increases both the amount dissolved and bound increase
Oxygen is ___ in water
not very soluble
Amt. of dissolved O2 vs. amt. bound to hemoglobin:
amount dissolved is negligible (0.3 mL/100 mL; (0.3 mL/dL)

compared to the amount bound to Hb
(19.5 mL/100 mL; 19.5 mL/dL).
The total oxygen content of blood
sum of dissolved and bound
At a PaO2 of 100 mmHg there is how much O2 bound to Hb?
19.5 mL O2 bound to Hb in every 100 mL of blood and 0.3 mL O2 dissolved in every 100 mL of blood for a total oxygen content of ~ 20 mL/ 100 mL
On average cells remove how much O2 from blood?
5 mL of O2 from every 100 mL of blood
With a cardiac output of 5 L/min, the body consumes on average how much O2?
250 mL of O2 per minute at rest
If oxygen were only dissolved in blood then it would take a cardiac output of what to meet the needs of tissue?
cardiac output of over 83 L/ min (0.3 mL O2
/100 mL x 83 L/min = 250 mL O2/min)

This is why the amount of O2 bound to Hb is so
important.
At an arterial PO2 of 95 - 100 mmHg: (Hb saturation %)
Hb >96% saturated and contains ~ 20 mL O2/100 mL blood
At a venous PO2 of 40 mmHg:
Hb is 75% saturated and contains ~ 15 mL O2
/100 mL blood
At all PO2 levels the amount of dissolved O2 is ___
small
normal oxygen levels of the air
160mmHg

Hb is almost completely saturated
Therefore, breathing 100% O2 would do what?
will add little O2 to Hb

The dissolved oxygen will increase from 0.3 mL/100 mL to 2.3 mL/100 mL.

This means the total oxygen content of blood would increase from ~20 mL/100 mL to ~22 mL/100 mL
For normal people, breathing 100% O2...
does not deliver significantly more oxygen to the tissue.
Increasing Alveolar Ventilation or V/Q:
Because at resting alveolar ventilation Hb is almost saturated with oxygen (~96%), increasing
alveolar ventilation or V/Q adds little additional oxygen to the blood
What is very effective at Oxygenating blood?

so...
Lungs

Therefore, the PO2 of arterial blood would be identical to alveolar air if it were not for the small physiological shunt that slightly lowers PaO2
During exercise what happens to mixed venous PO2?
decrease from the normal value of 40 mmHg as
additional oxygen is removed by the active tissue

However, the lungs are so effective in oxygenating the blood that even during strenuous exercise arterial PO2 returns to approximately 100 mm Hg
The effectiveness of the lungs in oxygenating blood is evident by what?
how quickly pulmonary capillary blood equilibrates with alveolar oxygen
Time it takes for a quantity of blood to flow from the arterial end to the venous end of a pulmonary capillary:
0.75sec
Within the first ___, capillary oxygen has equilibrated with alveolar oxygen. What does this mean?
0.25 sec

This means that oxygen equilibration is complete by the time the blood gets 1/3 of the way through the capillary
When blood increases (e.g. exercise)
there is still 2/3 of the capillary for exchange to occur
What equilibrates with the pulmonary capillaries?

So what can we say?
arterial and alveolar oxygen equilibrate within the pulmonary capillary

we say that oxygen is perfusion limited, not diffusion limited.

We can deliver more oxygen per minute to the tissue only by increasing perfusion
What does it mean that oxygen is not diffusion limited?
raising inspired O2 does not add significantly to the blood oxygen
What influences the binding characteristics of Hb for oxygen?
1. CO2 levels
2. H+ levels
3. temp
4. 2,3 BPG levels

CO2, H-ions and elevated temperature decrease the affinity of Hb for oxygen; So during times of increased tissue metabolism when these three factors rise, more oxygen comes off Hb
Red blood cells synthesize ATP solely via
glycolysis

They do not consume the oxygen that they carry
During glycolysis, what is formed?
2,3 BPG is formed from 1,3 BPG by a mutase and then converted to 3-phosphoglyerate bypassing the production of ATP
Under conditions of increased tissue oxygen need, describe what happens to RBC:
red blood cells make more 2,3 BPG enhancing the release of oxygen from Hb at the expense of
their own ATP synthesis
Elevation in any one of these four will shift the Hb-O2 dissociation curve to the ___, which does what?
right

decreases the ability of oxygen to bind to Hb
What does this RIGHT shift lead to?
This shift leads to

1) More oxygen being released from Hb at any PO2
2) An increase in the P50 (a decrease in affinity)
This rightward shift is appropriate because?
an elevation in these four parameters is what occurs in metabolizing tissue, that is, tissue that needs more oxygen.

So, the decreased affinity of Hb for oxygen increases oxygen delivery to the tissue.
How does a leftward shift in the Hb-O2 dissociation curve result?
when one or more of the four decrease
Anemia
a reduction in the number of red blood cells in the blood

This results in less Hb which means the blood holds less total oxygen.
What does Anemia do to the affinity of Hb?
The affinity (P50) of Hb does not change
What does Anemia do to the PO2 of blood?
the PO2 of the blood does not change

the % saturation does not change; the amount of dissolved oxygen does not change.
Carbon monoxide
binds 200x more strongly to Hb than does oxygen
When CO binds to Hb, two things happen:
1. oxygen binding capacity is reduced
2. it causes a conformational change in Hb so Hb is in its "relaxed" state, a state where its oxygen affinity is maximum
In the presence of CO, Hb holds ___ O2
and it holds it how?.
less

more tightly
Similar to anemia, what does CO poisoning do to O2 carrying capacity of the blood?

What else does it do?
reduce

CO also shifts the Hb-O2 dissociation curve to the LEFT increasing the affinity (P50 decreases) of Hb for O2

PO2 is unchanged
Hb comes in different forms (4):
1. Myoglobin: a single monomer of Hb; it binds a single oxygen; is present in slow (red) skeletal muscle; it serves to store O2 for times when PO2 is very low.

2. Fetal hemoglobin (hemoglobin F, HbF): this Hb has a higher affinity for O2

3. Hemoglobin S: is an abnormal variant involving a single amino acid substitution.
This substitution causes oxygenated HbS to crystallize into long fibers that change the shape of the red cell (cause it to sickle).

Non-crystallized HbS has the same oxygen affinity as normal Hb, but when it becomes fibrous, its affinity decreases.

As a consequence the oxygen carrying capacity of individuals with HbS is less than normal.

4. Methehemoglobin: the iron is in the ferric (Fe
+3) rather than the ferrous (Fe+2) form
which prevents O2 binding
Carbon dioxide is carried in the blood in three forms:
1. Dissolved: CO2 is 20x more soluble in water than O2so a significant amount of CO2 (5%) is dissolved in the plasma

2. Bicarbonate:

3. Bound: About 5% of the CO2 is bound to Hb forming carbamino-Hb
Bicarbonate:
The majority of CO2 generated by the tissue is converted to HCO3 in the blood as it passes through the systemic capillaries; this conversion occurs both in the plasma (liquid portion of the blood) and the RBCs.

Some of the HCO3 produced within RBCs is secreted in exchange for Cl; the movement of Cl into and out of RBCs is called the Cl-shift; HCO3
formation increases intracellular osmolarity
and causes RBC swelling; this is reversed during passage through the pulmonary
capillaries.

H-ions formed in the process bind to Hb which decreases its affinity for O2
Unlike the oxygen-Hb dissociation curve, the carbon dioxide-Hb curve is more
linear
Hb binds more ___ than ___
CO2 than O2


(notice values for CO2 on the Y-axis; 40's & 50's in contrast to a maximum of 20 mL/100 mL for O2)
).
Just as CO2 influences O2, binding to Hb...
O2 also influences CO2 binding. Oxygen bound
to Hb interferes with CO2 binding.

So, Hb in arterial blood holds less CO2 than Hb in venous blood.
The respiratory quotient (RQ)
ratio of CO2 produced to O2 consumed
For the metabolism of carbohydrates this RQ is:
1
fats and proteins
between 0.7 & 0.8.
Assuming an RQ of 1, describe O2 and CO2:
for every O2 removed from the blood one CO2
is added.

So if the PO2 changes from 100 mmHg to 40 mmHg as arterial blood gives up O2 one would
expect the PCO2 to change from 40 to 100 as CO2 is added
However the PCO2 of arterial blood only changes from ___. Why?
40-46

This is because a lot of the CO2 that is added to the blood by the tissue is removed from solution by binding to Hb and being converted to HCO3

Therefore, PCO2 does not increase a great deal (+ 6 mmHg) in venous blood as it passes through the tissue.