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Lecture 12

BIOC34H3 Lecture Notes - Lecture 12: Fetal Hemoglobin, Respiratory Minute Volume, Red Blood Cell


Department
Biological Sciences
Course Code
BIOC34H3
Professor
Stephen Reid
Lecture
12

Page:
of 6
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Lecture 12: Blood Gas Transport
1. Partial Pressures of Gases throughout the Circulatory System
In blood flowing through the pulmonary artery into the lungs, oxygen levels are relatively low (40
mmHg) and CO2 levels quite high (46 mmHg). Note: mmHg is often referred to as 'Torr'; they are
the same unit. The blood reaches the lungs, where it interacts with alveolar air. Alveolar air is not
the same as atmospheric air; atmospheric air has a PO2 of 160 mmHg and a PCO2 of 0.3 mmHg,
whilst alveolar air has a PO2 of 100 mmHg and a PCO2 of 40mmHg. There are several reasons for
this: firstly, gas exchange occurs through the capillaries in the alveoli with the atmospheric air
before it has a chance to reach the blood of the systemic circuit; secondly, there is mixing of the air
in the anatomical dead space; and thirdly, the alveoli are filled with water vapour as well, with a
relative humidity of approximately - and we have to subtract the partial pressure of water vapour
from the partial pressure of oxygen and carbon dioxide.
The blood flowing through the lungs equalizes with the partial pressures of the alveolar air (100
Torr O2 and 40 Torr CO2) and remains at these values throughout the systemic arteries. When the
blood enters the systemic capillaries (tissues) and begins oxygenating the tissues and carrying
away carbon dioxide, the partial pressure of oxygen drops to 40 Torr and the partial pressure of
carbon dioxide rises to 46 Torr. Within the mitochondria oxygen levels can be as low as 1 Torr.
The deoxygenated blood flows through the venous system back to the right side of the heart,
maintaining these partial pressure values until it returns to the lungs.
2. Perfusion versus Diffusion Limitation
In human lungs), the uptake of O2 and the excretion of CO2 are perfusion limited. This refers to
the fact that the limiting factor in the oxygenation of our tissues (and the removal of CO2 from our
tissues) is the rate of blood flow to our lungs and tissues. However, some animals such as fish, and
humans in certain circumstances, are instead diffusion limited, meaning that the limiting factor in
oxygenation of the tissues is the diffusion rate of oxygen from the lung gas into the blood flowing
through the lungs.
The rate of O2 uptake, and CO2 excretion, is a function of the distance the blood has to travel
through the pulmonary capillaries. Within the first third of the length of a pulmonary capillary, the
blood has changed from being deoxygenated and high in CO2 (40mmHg O2; 46mmHg CO2) to
being oxygenated and low in CO2 (100mmHg O2; 40mmHg CO2). What this means is that we have
a large reserve distance in the lungs for gas exchange; two thirds of the capillary length is not even
used in normal gas exchange. In very highly-trained athletes, at the peak of their performance,
however, diffusion limitations do begin to apply.
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3. Determination of Alveolar Ventilation
The rate of gas exchange at the lungs depends upon our metabolic demands. The amount of
oxygen that is being consumed, or carbon dioxide excreted, will affect the amount of alveolar
ventilation. The ratio of CO2 production to O2 consumption in our tissues is called the respiratory
quotient and it is a measure of our metabolic rate (in the lungs this ratio is referred to as the
respiratory exchange ratio). Regular breathing which is sufficient to meet our metabolic demands
is called eupnea or eupneic breathing. When metabolic demands increase, for example during
exercise, alveolar ventilation must increase to meet this heightened demand; this is called
hyperpnea. Apnea is the term for the absence of breathing, and dyspnea is the term for difficult
or laboured breathing.
4. Hyperventilation and Hypoventilation
Everyone has heard the terms hyperventilation and hypoventilation before; colloquially we use
these terms to refer to an increase or decrease in breathing, but clinically they are defined in terms
of blood gas levels. If breathing is reduced enough that the partial pressure of oxygen in the arterial
blood falls below 100mmHg and/or the PCO2 rises above 46Hg, we refer to this as hypoventilation.
If breathing increases such that PO2 rises above 100mmHg, and CO2 falls below 40mmHg, then we
refer to this as hyperventilation.
5. Daily Oxygen Consumption
Minute ventilation is about 6 L per minute. Of this 6 litres of air that we breathe every minute,
some ventilates the dead space of the conducting zone so only approximately 4.2 L per minute
actually reaches the alveoli. We know that air contains about 21% oxygen so therefore
approximately 882 ml (4 200 ml x 21%) of oxygen reaches the alveoli every minute. Only about
250 ml of this 882 ml of oxygen actually diffuses into the blood. If we multiply this by the number
of minutes in a day, we find that per day, a human consumes about 360 litres of oxygen. We can't
get this amount of oxygen to our tissues by relying on oxygen dissolved in the blood - if we did,
cardiac output would have to be 83.3 L of blood a minute, far more than the 5 L of blood actually
pumped per minute. So how do we get so much oxygen to the tissues?
6. Haemoglobin
The answer is haemoglobin. Haemoglobin contains 98.5% of the O2 in the blood. Each molecule
of haemoglobin consists of 4 globin subunits (2 alpha and 2 beta) with each subunit containing a
heme group which consists of a porphyrin ring with an iron molecule in the centre. The iron
molecule is the site of O2 binding so each haemoglobin molecule can bind up to four O2 molecules.
Fetal haemoglobin is slightly different; it contains different globin molecules and fetal
haemoglobin has a greater affinity for oxygen than the haemoglobin of the mother allowing for
efficient oxygen transfer from the maternal blood to the fetal blood.
Sickle-cell anaemia is a genetic disorder that causes red blood cells to be abnormally ('sickle')
shaped. It is caused by the production of an abnormal form of haemoglobin and results in the red
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blood cells being less efficient at O2 transport, as well as being viable for shorter periods of time
and tending to clog blood vessels. A single-point mutation in the haemoglobin beta chains, causing
haemoglobin molecules to adhere together in a distorted fashion, is the primary cause. Fatigue is
the most common symptom of the disorder, but can severely limit exercise and ability to undertake
strenuous activity.
7. Linking Oxygen and Carbon Dioxide Transport in the Blood
Carbonic anhydrase (CA) is an enzyme that is found throughout the body. CA’s function is to
catalyse the reversible hydration/dehydration reaction whereby CO2 reacts with water to form an
H+ ion and a HCO3- ion. Carbonic anhydrases are found in the red blood cells, in the kidney tissues
(where it is important for bicarbonate reabsorption and acid-base balance), in the parietal cells
lining the stomach and in other tissues. However it is not present in the plasma.
The CO2 hydration/dehydration reaction (H2O + CO2 HCO3- + H+) is critical for O2 and CO2
transport in the blood.
The other reaction involved in this process describes the binding of oxygen to haemoglobin.
These two equations summarize the relationship between CO2 and O2 transport in the blood and
we can model gas exchange in a red blood cell in the lung (and tissues) using these two equations.
In the lungs O2 diffuses into the blood and then into the red cell. It binds to haemoglobin, and as
shown in the equation, causing haemoglobin to lose H+ ions. These free H+ ions react with HCO3-
ions in the cell (these enter the cell via chloride bicarbonate exchanger gates) to produce CO2 and
H2O, and then this CO2 diffuses out into the alveolar gas and is lost as we expire.
In the tissues, CO2 diffuses into the red cell and reacts with water to form a proton and a
bicarbonate ion. The proton then binds to oxygenated Hb causing the oxygen molecule to come off
the Hb molecule. It is then free to diffuse into the tissues.
Both the CO2 hydration/dehydration reaction and the oxygenation/deoxygenation of Hb are
influenced by H+ ions. Given this, pH can have a significant effect on oxygen-haemoglobin
binding.
CO2 in the systemic arterial blood can be found in many forms, but primarily (89.6%) it is found as
bicarbonate ions in the blood. 5.5% is dissolved in the blood directly, and another 4.8% is bound to
haemoglobin.