script #9 gas transportation

8/3/2019 script #9 gas transportation

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In this lecture, we will talk about gas transportation in the blood and we will also

give you an idea about regulation in the respiratory system.

Gas Transportation

The composition of air that you inspire will have the pressure of 150 mmHg by the

end of inspiration which is different than the end of expiration. It will give you an

alveolar composition in that space, so youll have the atmospheric composition

that will be a little bit different, because of the water vapor.

We did talk previously about the major force principle for gas diffusion which is

thepartial gradient pressure. According to this principle, O2 will have the pressure

of 140 mmHg in the lungs area and the same pressure in the tissue. The O2 will go

from the lungs to the tissue, as the carbon dioxide CO2 is higher in the tissue than

in the pulmonary arteries.

Carbon Dioxide

Lets start with CO2 because its easier to discuss. CO2 transports in the blood in

differentforms:

60 % of CO2 is in form of H2CO3

30 % of CO2 is a compound with hemoglobin

10 % of CO2 dissolved in the plasma

CO2 as carbonic acid (H2CO3), which is not a stable compound, can be dissociated

to hydrogen & CO2 , CO2 can bind to hydrogen to form H2CO3. Thats why the

majority of CO2 in the blood is in the form of H2CO3.

Now the most important gas is not CO2 but O2. after diffusion, O2 will be in the

blood and it will cross the cytoplasm membrane of RBCs. 97% - 98% of that O2

will bind to the hemoglobin molecule, each hemoglobin molecule has 4 sites to

bind with O2.


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Hemoglobin is a protein with a long polypeptide structure of amino acids. And as

we remember from biochemistry it has 4 subunits, 2 of them is called alpha and 2

of them is called beta. The functional one for oxygen binding is thebeta.

Forms of hemoglobin

Hemoglobin has 2 forms :

1- Liking O2 (exposed sites)

2- Disliking O2 (released sites)

The benefit of this is that when the hemoglobin is in the area of the lungs (the

pulmonary arteries, capillaries and alveolar structure) where thePulmonary

Circulation occurs. The hemoglobin will be in the liking form, because the function

there is to catch the O2 from the lungs down to the tissue. Then (in the tissue) it

changes to its disliking form so the hemoglobin will start to release the oxygen in

the tissue.

Factors that can change the hemoglobin form

Different factors can change the form of the hemoglobin. Changing here is not

about being exposed or closing the sites, but its about increasing or decreasing

the power or force of the hemoglobin to catch the O2, which is calledaffinity

(meaning strength). So the affinityof the hemoglobin describes its capability of

holding O2. Hemoglobin with high affinity catches O2 well and that with low

affinity releases O2 somehow, easily.

So, what are the factors that change the affinity of the hemoglobin?

-CO2, Hydrogen concentration,Temperature and BPG (2,3-bisphosphoglcerate).

The increase of one of these factors or more than one will decrease the affinity of

Hb (Inverse relationship).


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Note: In the pulmonary circulation we have continuous ventilation -O2 supply,

CO2 deplete. if one site of the Hb binds one oxygen the other 3 sites will have

more affinity to bind with the remaining oxygens, and when it binds to the second

oxygen the other 2 sites will have more and more affinity to bind to the remaining

2 oxygens.

1- CO2

Depleting of CO2 means decreasing its concentration in the blood , and according

to the ventilation concept we mentioned earlier, it will increase the affinity of Hb.

2- Hydrogen Concentration :

From studying PH we found that by reducing the CO2 concentration, the

Hydrogen concentration will be reduced as well because CO2 is a volatile acid. So

when you leave out CO2, the hydrogen will be less and the PH will be alkali. Thus,

increasing PH will give us higher affinity, and decreasing PH lowers the affinity

because its similar to the increase and decrease of hydrogen concentration.

H+ , CO2 , PH , affinity

3- Temperature :

Continuous ventilation happens when the blood comes to the lungs. It will cool

the blood vessels and the blood itself like when you open the door and the

windows of the room so youll have an airway that cools the room due to the low

temperature of the air itself. This continuous ventilation will decrease the

temperature in the pulmonary circulation in your body.

Note: we can conclude so far that those 3 factors are not favorable in the

pulmonary circulation.

4- BPG (2,3-bisphosphoglcerate).

we still dont know the way it works in physiology but its important in pathology.


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Fig. 12-23, p. 389

Alveoli

Pulmonary

capillary

blood

= O2 molecule

= Partially saturated hemoglobin molecules

= Fully saturated hemoglobin molecules

Fig. 12-25, p. 392

Tissue cell Alveolus

Plasma

From systemiccirculation

to pulmonary

circulation


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In the tissue :

The metabolic reaction occur in the cell , produce energy , produce heat , so the

Temp will be closer to the tissue , and higher the Temp .

If we are talking about nerve or muscle cell ( the places where we need more O2 (

, the Temp is more higher , so that will decrease the affinity that will cause the

release of oxygen . metabolic reaction in the cell will produce CO2 always.

Nutrients + O2 + H2O + Enzyme CO2

So CO2 level will be more in the tissue that will decrease the affinity .

Increasing CO2 will cause it bind to H from H2O to produce H2CO3 ( with the help

of Enzyme or carbonic anhydrase in the tissue ,

and the H2CO3 will disassociate to H2 and CO2

CO2 + H2O

>

H2CO3 H2 + CO2

SO we have more CO2 >>> more H >>> Less PH

So these Factor will increase the affinity of the Hb to bind to oxygen

So whenever Hb move to pulmonary circulation >> higher affinity to catch O2

whenever it is in the tissue >>it release oxygen

AND THIS IS THE GOALS OF RESPIRATION( take the O2 from atm , release the O2

in the tissue )

Carbonic anhydrase

Enzyme


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How fast that reaction occur ?

This is a capillary which we divide it into 3 thirds >>>

1/3 1/3 1/3

When Hb moves on the first part ( first third distance )it is more than enough time

to have 100% saturation of Hb , So when Hb is move to the pulmonary circulation

doesnt take long time to have 100% saturation .

What is 100% saturation ??

When the 4 sites of the Hb are fully occupied by O2

Now the Qs is : How many molecule of Hb in each RBC ?

Answer : It is 250-300 thousand molecule

( according to some calculation the Dr did )

FIGURE 12-22 / SLIDE 34

97% bound with Hb

3% swimming in the plasma

Very fastHb


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Fig. 12-22, p. 388

Average resting

PO2 at systemiccapillaries

Normal PO2 at

pulmonarycapillaries

1 g Hb 1.34 ml of O2 ( total weight of the 4 oxygen molecule that binds to 1 g

Hb

So

1 g Hb 1.34 ml O2 / dL

50 g Hb 12 ml O2 / dL

So , at 1/3 distance the blood cell will be fully saturated before it reach the second

third or the third third ( last part of capillary ) , so what is the need of this parts

without binding to O1 ???

Bcz GOD knows that sometimes when u r running or stressful the heart will pumpur blood much faster , so the blood flow instead of X it might be 2X more , So , in

this case GOD doesnt want this blood cell to leave the lungs without oxygen

{ ABNORMALITIES IN BINDING OXYGEN }

** CARBON MONOXIDE POISONING

It is very common especially in poor countries bcz they dont have a central

heating > when we are in winter people try to warm themselves , one way of

warming is burning wood or kerosene , the result of that fire is producing the CO2


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and CO ( carbon monoxide ) . This CO Loves this site of oxygen more than O2

Loves the sites ( higher attraction )

Bcz of that > in the presence of CO the O2 lose its affinity to bind to the sites

For example : if there are 250 O2 and 1 CO the 1 CO will win the 250 , and O2

will lose the site of binding

CO binding affinity to Hb is stronger 250 times more than O2 affinity

Now let me give you what will happen after CO poisoning , people die peacefully ,

they dont feel pain , dont shout , dont cry , they just sleepy and it is the end of

their life !

Study the following figures well :

Fig. 12-24, p. 391

Arterial PCO2 and acidity,

normal body temperature

(as at pulmonary level)

PCO2

Acid (H+)

Temperatureor

2,3-Bisphosphoglycerate

(as at

tissue

level)


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pO2

% saturation

9 ml O2 / dL

20 ml O2 / dL

100 mmHg40 mmHg

16 ml O2 / dL

19 ml O2 / dL

About the last figure:

1) The partial pressure of O2 in the blood could be zero when we have heavyexercise m when all the O2 are consumed

2) The pressure at artery part, at full saturation is = 100 mmHg and theamount of O2 at that time is 20 ml

3) The pressure at veins part is = 40 mmHg and the amount of O2 at thattime is 16 ml

NOW the Qs is :

( What is the amount of O2 that is released , and we usually need

It ?)

**The Answer >>

Artery part

= saturated blood

= Artery blood

= Oxygenated blood

= 100 mmHg

Veins part

= unsaturated blood

= vein blood

=deoxygenated blood

= 40 mmHg

Capillary


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the amount Of realized O2=

the amount that inter the amount that leave

So , here >> the amount of realized O2 = 20 16 = 4 ml

Now

Lets assume that the affinity of Hb is higher or lower than normal

The amount of

realized O2

The curve

Higher affinity 20-19 = 1 ml Shift to the left

Normal affinity 20-16 = 4 ml normal

Lower affinity 20-9 = 11 ml Shift to the right

Lets say a normal person has 15g of Hb, after a CO poisoning he inhaled a certain

amount of CO (not much). Lets assume that half of Hb was bound to CO

(0.5*15=7.5 g/Hb). We have only 7.5g/Hb available for oxygen and the other half

it appears as it is absent because they come to the lungs they dont take O2, and

the go to the tissue and they dont release oxygen (thats why we use the term

absent).

So, we have half the amount of the Hb available, so the full saturation will actually

be half the normal one: not 20 mL but 10 mL as the full saturation.

So again: why this curve got changed and reduced to the half?


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-because half Hb are available for the oxygen and the other half will be lost.

one half is lost by CO binding the other half, affinity is decresed. The other half

has a higher affinity because of CO binding so the curve will shift to the left.

Now lets ask ourselves this question: with carbon monoxide poisoning, how

much oxygen in the arterial blood coming to the tissue and how much oxygen

released to the tissue..??

The same simple question..

In here arterial blood have the partial pressure of 100 mmHg so the amount of

oxygen is 10 mL, when the blood comes to the tissue it carries 10 mL because its

fully saturated condition means only half the amount of the hemoglobin is

saturated. Now we want to take some of that oxygen to the tissue..

when we take that, the partial pressure of oxygen here is 40 mmHg so the

amount which matches this point on the figure is another 10 mL. So when you

subtract them you get zero mL of oxygen released. So in carbon monoxidepoisoning because 1) the affinity of the curve is shifted to the left, 2) the amount

of the Hb is less the other half is carried by CO, we will not have any oxygen

released to the tissue . And this is whats going on while people are sleeping

peacefully inhaling the carbon monoxide from the stove and when the carbon

monoxide concentration increase and increase, reaching that point so theres no

O2 to the nerve cells.. the point here.. Nerve cells

we have a center for respiration, and this center is capable of sensing how much

oxygen is present in your tissues. If it is low, it will increase your ventelation tosupply the tissue with more oxygen. But there is a cut of point limit when we have

zero oxygen to the supply the respiratory center itself, in this case, the respiratory

center got killed and its work is stopped. We dont do more ventilation, we

stop it.

at the same time, we lose our conscious. So these people, when they reach that


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level of No oxygen and the carbon monoxide is full they will lose their conscious

which is good for not feeling the pain of dyeing.

This the best way to commit suicide, (please believe the doctor in this). People

who want to die peacefully set in the garage and turn on the cars and inhale the

smoke thats coming out of the car which is full of carbon monoxide.

Carbon monoxide, what it does??

It will bind ., very strong, and it will increase the non bound for

oxygen, it will increase the affinity. So that increased affinity will shift the curve to

the left and so, people die.

we hear a lot of stories about whole families die because of this. Securing all the

windows and the doors and sleeping while the stove is turned on. This is the

carbon monoxide poisoning.

Another case is Anemia. Therere different types of the anemia but well talk

about the common one, which is the iron deficiency anemia. The normal amount

of oxygen is 20 mL of oxygen in arteries and 60 mLs in veins and 4 mLs was

utilized. Lets assume this child has anemia.

in other words when we major the Hb content of that child it will be lower than

the normal. The normal Hb is said to be 50 % g/dl just for the simple discussion

we repeat it again in front of you, lets assume we major that Hb in the patient is

7.5 so half of his Hb is lost, not lost because of carbon monoxide bound because

its not there! Iron deficiency they are not able to produce and synthesize enough

Hb so the amount is half , because its half so we will have 10 ml of the full

saturation this is the curve for this patient.


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Now the problem is the same when we calculate the utilization. This is 10 ml and

this is 8 ml so 10 8 = 2 ml from each dl, this is bad, normally this child needs

more than 4 ml from each dk. What he gets only half of it. Now if you ask mepractically all these anemic patients especially children they are not bad in their

feeding and sign and symptoms, theyre playing theyre normal but when you

major the Hb itll be lower, you discover them by screening or majoring that. Why

they dont feel bad? Because somehow when the HB is lower and the other half is

absent completely, the remaining Hb decreases its affinity. In the CO poising the

opposite; the remaining half increase their affinity, here the existing Hb as

homeostatic function or reaction it will decrease the affinity of Hb, because its

decreased that means the curve shifted to the right (left strongerright weaker)so that curve will be this on but the saturation will will stay 10 ml (full) of

oxygen now because this shift to the right lets calculate the oxygen utilization

in the artery the amount of oxygen is 10 ml when it comes to the tissue

When it leaves the tissue its 40 mm Hg. So the amount of oxygen in this curve

will be about 6. So if you see there is compensation by shifting the curve to the

right youll get better amount of oxygen released even the absolute total amount

to oxygen is half instead of 20 we have 10 so the patients are good becausesomehow the curve is shifted to the right, after a while it will go back to the

normal affinity and that will cause a reduction of oxygen utilization. So this is the

other case of oxygen Hb dissociation curve.


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Fig. 12-26, p. 396

Pons

Pneumotaxic center

Apneustic center

Pre-Btzingercomplex

Dorsal respiratorygroup

Ventral respiratory

group Medulla

Ponsrespiratory

centers

Medullaryrespiratory

center

Respiratory

controlcenters in

brain stem

Lets go to the last topic of respiration:

We already know how the first step, ventilation, is physiologically conducted, and

how diffusion occurs between the glands and blood vessels, and between blood

and tissues as the second step to the process. We also know how gas is

transported in the blood by carbonation, where CO2 either binds to hemoglobin,

or it dissolves. 98% of O2 can also bind to hemoglobin, and the 2% binds to the

plasma.


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Table 12-5, p. 397

Now lets see how we can control and regulate the three steps of respiration:

Since we are talking about regulation, we must mention both the central nervous

system and chemical regulation. Let me start with the central nervous system.

The regulation of human breathing has to major parts: the first one is your will to

stop breathing. If you want to stop breathing you can. If you ask yourself to hyper

ventilate, you will. For how long does this go on for? It goes on until your nervous

system tells you to stop.

The second part which is involuntary is located in the medullar open gate bone in

the central nervous system. We will explain this in brief, I will give you the main

idea of regulation but not in detail.

We have a collection of nerve cells, they are special in respiration which means

they send a signal to the inspiratory muscle, and then the muscle will contract.

There is another collection of nerve cells, the expiratory nerves, but the benefit is

that when the inspiratory neurons are firing, the expiratory are inhibited, and

when the the expiratory are firing, the inspiratory are inhibitedbecause you cant


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do both opposing actions together, I was talking about forcible breathing but in

normal breathing I discussed before in the diaphragm contraction and relaxation,

just inspiratory neurons fire with that muscle to contract the diaphragm then a

release of diaphragm, what causes the expiration recalling tendency elastic

tissues and the intra-pleural pressure which becomes less negative.

There is no brain control for normal quiet expiration at all, the only control for

normal inspiration its an on and off signal and if we cut all the neurons up and

down, this center for normal quite breathing it will fire on and off ,on and off. In

physiology we call this circadian rhythm, the same thing applied to your eyes

when they are closed and opened or like when you sleep and wake up. We need

to balance this rhythm to make our health proper, if we dont balance those 2

facts inhibition and estimation (on & off) we will die, so the respiratory central(inspiratory neuron and expiratory neurons), are the major neurons but they are

not enough, another thing is needed, like sometimes we need hypo and hyper

ventilate and sometimes we need to stop a little bit, this is not coming from the

brain but from the outside the brain.

Fig. 12-27, p. 397

Sensory

nerve fiber

Carotid sinus

Carotid artery

Aortic arch

Sensory

nerve fiber

Carotid bodies

Aortic bodies

Heart


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We have different receptors that are located in the most beautiful area of our

bodies: the aorta and carotid artery. These receptors have one ultimate goal: to

sense the amount of oxygen and the amount of CO2 in the area. If this is the case,

let us assume that these receptors were found on the muscle fiber.

In the muscle fiber, oxygen will be 100, 40. If the muscle is moving it will be 100,

10 and 100, 0 if the muscle is running, meaning they cant control the normal

situation. In the normal situation, the muscle moving will have zero oxygen, while

a still muscle will have 40 mm mercury of oxygen. So the normal range is between

0 40 mm.

If they were located there, they would send a wrong message to the brain. Notice

the aorta and carotid artery. The blood flow is very fast and this is one of the

factors. The second factor is the fact that we dont have an excitable membrane

in the carotid artery. In other words, we dont utilize and produce much oxygen

there. This would be the same case if the receptors were sensitive to CO2 and we

put them on any tissue, at times we will have a lot of CO2 (the metabolic reaction

is high), and times were metabolism is low, meaning that the normal range will be

high. So the receptors shouldnt be in wrong places, they should be here where

the oxygen content is 100 and the CO2 content is 40 mm.

When the oxygen content is low and CO2 is high, then there is something wrong in

our respire system. When we dont have enough oxygen to breathe, the aorta and

carotid artery will have lower oxygen. This makes them sense the low content of

oxygen, meaning they should interact.

Back to the tissue, it was normal to have zero oxygen and abnormal to have

60mm mercury, because we dont utilize oxygen here. At the same time, when we

have more than 50 mm mercury of CO2 here and here, it means something is

wrong in the metabolic action which will increase the amount of CO2 which isbeyond the capacity of the respire system to expel out. A message to the brains

center will be sent telling the brain to interact, where low O2 and high CO2 will

cause hyper ventilation, where we will expel CO2 and get more O2, then change

the normal concentration of O2 and CO2 in the blood to the norm, these

receptors will quiet down.


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This is the function of our respire center in the brain. They are working day and

night in the normal case, and receptors here to sense the reduction of O2 or the

increasing of CO2 to interact. So we have the regulation of the respite center and

the peripheral which are the respire receptors. There are other factors too such

as pain. So when you sense pain you will hyper ventilate so the pain will affect the

respiratory regulation. Sudden cold temperatures will also stop the breathing.

Drugs such as sleeping pills or pain killers in large concentrations will also cause

hypo ventilation. Under anesthesia will also cause the control of respiration to

stop. That is what happens when people are anesthetized under operations and

we do artificial breathing, because the respire center does not send signals.

Paraphrased by : Marwa Al-Halalmeh & Eman Nazzal

Thanx A lot for : Malak joudeh & Noha Ghazal

. Good luck

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script #9 gas transportation