CO2 production and pathways
C6H12O6 + 6O2  6CO2 + 6H2O + energy
So for each molecule of O2 consumed in carbohydrate metabolism , a molecule of CO2 is
produced , that's mean the ration in carbohydrate metabolism is 1:1 , but the respiratory
exchange ratio equals 0.8 and that's because of the lipids and proteins metabolism , they
consume oxygen more than they produce CO2
The respiratory exchange ratio = CO2 " out "/ O2 " in "  200/250 = 0.8
* pCO2 : partial pressure of CO2
How the CO2 reach the lung ?
1. Dissolved in plasma ( pCO2 * solubility of CO2 ) ( 10% )
* the solubility of CO2 is 20 times
more than oxgen ( 0.003)
The arterial pCO2 is 40 mmHg and the solubility is 0.06 , so the dissolved CO2 in the
plasma  40*0.06 = 2.4 ml
2. Bound with hemoglobin ( carbaminohemoglobin ) in RBC (20% )
3. As carbonate in the plasma ( 70% )
The CO2 enter the RBC and bind with H2O forming H2CO3 ( catalysed by carbonic anhydrase )
and then the bicarbonate ( H2CO3 ) will dissociate to carbonate ( HCO3- ) and the carbonate
diffuse into the plasma in exchange for chloride ( chloride shift )
Control of breathing
ABGs : Arterial Blood Gases
The respiratory controller system which is located in the medulla oblongata has a main function
which is maintain normal ABGs ( homeostasis )
Normal ABGs : ( pO2 = 90 – 100
mmHg , pCO2 = 40 mmHg , pH = 7.4 )
The respiratory controller system can maintain homeostasis by increasing or decreasing the
Ventilation
Note : ventilation is breathing , so when we say hyperventilation we mean increasing the
breathing rate so we can make the alveolar air as same as the atmospheric air ( to make the
ABGs higher )
So if pO2 in the alveoli was 100 and a hyperventilation occurs , it will become 150 mmHg inside
the lung ( why not 160 as the atmospheric air ? ) because when the air enter the bronchioles ,
the water vapour is added
the water vapor partial pressure is 47 , so 760 – 47 = 713 mmHg ( that's the air pressure when it
enters the lung ) and as we know , 21% of the air is oxygen => 713 * 21% = 150 mmHg ( that's
the maximum pO2 in the alveoli )
and the pCO2 will decrease as the ventilation increases ,
until it become zero ( the numbers in this figure is not
accurate , it's just for clarification )
( no matter how much you increased ventilation , you can't
make pO2 more than 150 )
Respiratory minute ventilation = tidal volume * respiratory rate
Tidal volume : lung
volume
0.5 * 12 = 6 litres ( 6 litres of fresh air enter the lung every minute )
the half litre that is in the lung is divided into 350 ml alveolar air and 150 ml anatomic dead
space air , when we multiply each one of them by the respiratory rate (12)
The alveolar ventilation = 0.35 * 12 = 4.2 litres
pO2 alveoli = pO2 arterial
The anatomical dead space ventilation = 0.15 * 12 = 1.8 litres
Important note : when we increase the ventilation , the pO2 will increase , but at certain point ,
no matter how much we increase ventilation , it pO2 will not be affected ( the point is 150
mmHg )
We increase ventilation by increase the contraction of the diaphragm , and the diaphragm is a
skeletal muscle , that means it needs motor neurons .
( if the diaphragm stop
The motor neuron that control the diaphragm called phrenic ( phrenic working , we die )
means diaphragm ) nerves , their soma ( cell bodies ) are located in the spinal cord in the neck
between C3 – C5 and they can't produce action potential by itself , they need an action potential
from the brain to tell them what to do , the action potential that comes from the brain has a
rhythm , it excite the phrenic nerves for 2s ( contraction of the diaphragm , inspiration ) then stop
for 3s ( relaxation of the diaphragm , expiration ) , that makes the respiratory cycle 5s.
the medulla is part of the brain stem , it has collections of neurons , some of them are
responsible for the heart , others for the vascular system , and it also has the respiratory
controller center . In the medulla , there's two collections of neurons responsible of respiration :
the dorsal respiratory neurons : they stimulate the phrenic neurons ( inspiratory neurons )
the ventral respiratory neurons : they ( inspiratory and expiratory neurons )
during the quit breathing ( usual breathing that you're doing right now ) we don't need expiratory
neurons , so the activated neurons are the dorsal
during exercise we use an accessory neurons connected to the sternum , those neurons fed by
the ventral respiratory neurons
the dorsal and the ventral groups has pace maker activity , that means they initiate action
potential by themselves
Quick review :
The action potential is produced in the medulla , in the dorsal respiratory group ( usually ) , the
impulse travels to the spinal cord in the neck ( between C3 – C5 ) and it synapse there to the
second neuron ( phrenic neurons ) , the phrenic neurons reach the diaphragm and stimulate it
Note : when CO2 increase the H2 will increase , how ?
We said that the CO2 bind to H2O to form H2CO3 , a dissociation occurs ( H2CO3  H+ + HCO3) So , if the concentration of CO2 increased , the Hydrogen will increase too )
ABGs role in respiratory control system
In the medulla there's also a chemosensitive neurons that are sensitive to hydrogen , when
acidosis occur ( increasing hydrogen concentration in the blood and that means the increasing
CO2 concentration by default ) it will sense it , then alter the dorsal respiratory neurons , and the
ventilation will increase to bring more O2 to the blood and remove CO2
When the ventilation increase , the CO2 concentration in the blood will decrease , so the
reaction will go in the opposite direction ( H+ + HCO3-  H2CO3 , then bicarbonate will give H2O
and CO2 to cover the loss ) and if you noticed , the hydrogen concentration decreased to cover
the loss of CO2 ( it will return normal ) , and the chemoceptor in the medulla will sense it and
stop stimulating the dorsal group  the ventilation decreased
Those chemoceptors alter the dorsal group , if the pO2 became less than 60 mmHg , or if
the pCO2 became more than 40 mmHg
Which one is more efficient CO2 or O2 ? ( read the next paragraph )
So, if you stop breathing ( voluntary ) the pO2 start to decrease until it reach 75 mmHg , and the
pCO2 start to increase until it become maximally 50 mmHg , and the ventilation will increase
involuntary ( why ? ) As you noticed the pO2 didn't reach the dangerous level ( less than 60 ) so
it's not enough to motivate the involuntary ventilation, but the increment of pCO2 is more
effective , it reaches a dangerous level ( 40 or more ) which will alter the dorsal group and
ventilation by default . ( the change in CO2 concentration is more effective )
Can you kill yourself by stop breathing ?
As we know , the diaphragm is skeletal muscle , that means it's voluntary muscle , so can you
shut it off ? yes you can , but for not for long time !! when you stop the contraction of the
diaphragm voluntary ( the order comes from the cortex ) the pO 2 will start to decrease , and the
pCO2 and pH will start to increase , but the increment of the CO2 is more effective than O2 , so
when CO2 reach 40 mmHg or more , hydrogen will increase in the blood and alter the
chemosenstive neurons in the respiratory controller center in the medulla , which will alter the
dorsal group more than the cortex does ( when you stop breathing ) and thus you will breath
involuntary .
Note : Chemoceptors in the medulla are sensitive to hydrogen and by default CO 2
Quick review : the gas that control the respiratory system the most
, is CO2 not the O2 because the CO2 dissociation curve is linear (
any increment in pCO2 will cause an increment in the
concentration of CO2 in the blood " the saturation of CO2 " ) but
the O2 dissociation curve is sigmoidal ( if the pO2 become more
than 100 it will not affect the saturation of O2 in the blood and if it
decreases less than 100 it will affect it , unless it become less than
60 )
* notice that between 100 – 60 mmHg there's no massive affect , that's why it's not the most
affective gas in the respiratory system .
Diver hyperventilate to washout CO2 from the blood ( make 20 instead of 30 for example ) and
thus they can stay in the water for longer period of time , but this might cause hypoxia when
he's in the water because of lack of oxygen
How the respiratory controller system monitor the ABGs :
1. The major arteries ( aortic and carotid ) sense oxygen in the blood and tell the dorsal group (
how come a cell can sense the arterial blood flow ) because they have very high blood flow ,
what does this mean ? as you know , 40% of our weight is skeletal muscles , that's 28 kg if your
weight is 70 kg , those muscle take 1 L of blood , let us say 1400 ml , that means each gram
consume 0.02 ml of blood , but the carotid bodies (it weights 25-29 mg ) take 20 ml of blood .
(how?) The arterial pO2 is 100 – 95 , in capillary 40 , in vain 40 , but the carotid cells have there
own artery that's how they can sense the change in arterial pO 2
Carotid bodies sense oxygen more than other gases but remember that chemoceptor ( in the
respiratory center ) sense hydrogen and CO2 more than oxygen
During exercise ventilation is driven by the receptors in the moving muscles and joints but the
ABGs are normal of course
Done by Suhaib Shroosh
Special thanks to Sumaia Nsour