Respiratory
I. Anatomy
A. Overview of airflow: a day in the life of a molecule of O2:
Our O2 molecule, as part of the air, enters through the nostril/external naris. Passes
through the internal nasal cavity, flowing between the nasal conchae. On the way, it's
cleaned by hairs, warmed and humidified. Travels through the pharynx at the junction of
the oral and nasal cavities, through the lanrynx, down the trachea. On the way, debris is
trapped by mucus. It will enter one of two major branches of the trachea. One branch will
take it to the left lung, the other branch will take it to the right. It has entered the brachial
tree, and it will continue on through a series of smaller and smaller branches of bronchi
and bronchioles, until it finally reaches an alveolus, a tiny sac. It will cross the membrane
of the alveolus and enter the blood, where it will be picked up by a hemoglobin in a red
blood cell. Eventually, it will be taken in by a body cell and used to help make ATP in
the Electron Transport Chain. As a preview to chapter 25, once it's been used in the
Electron Transport Chain it will join up with 2 H's as part of water!
B. Structures to review: bronchial tree, alveoli, respiratory membrane, pleurae
II. Respiratory Physiology
A. External and internal respiration (definitions, you can look these up)
B. Pulmonary (lung) ventilation
1. Background- how and why gases move in particular directions
a. Gas Pressure and Volume- pressure of gases is higher in small
containers (small volume) than in large containers (large volume). Boyle's
law states this as an equation: P=1/V (pressure is inversely related to
volume) This relates to respiration, because we have a container that we
can change the volume of: our thoracic cavity, which holds our lungs. So
when we contract our diaphragm, the size (volume) of the thoracic cavity
increases, and gas pressure in the thoracic cavity decreases (and viceversa).
Like particles in solution, gases move from an area of high pressure
(concentration) to low pressure. So, when we increase the volume of the thoracic
cavity, we cause the pressure in our lungs to dip below atmospheric pressure.
Since gases move from higher pressure to lower, gases will move from the
atmosphere into our lungs (and vice-versa).
b. Respiratory and atmospheric pressures
i. Intrapulmonary pressure- pressure within the lungs.
During inhalation, the thoracic cavity expands (gets bigger), the
pressure in the lungs dips below atmospheric pressure, and air
moves into the lungs. Again, this is simply driven by pressure
gradients: air moves from higher pressure (atmosphere) to lower
pressure (lungs). When we exhale, the thoracic cavity shrinks, the
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pressure in the lungs rises above atmospheric pressure, and air
leaves the lungs as it follows its pressure gradient.
ii. Intrapleural pressure- pressure within the pleural cavity.
Pressure within the pleural cavity is maintained below that of the
lungs at all times. This prevents the lungs from collapsing.
3. The muscles of inspiration (inhalation) and expiration (exhalation)
a. Quiet breathing: during inspiration, the diaphragm and the
external intercostals contract, expanding the volume of the thoracic cavity.
This is an active process, since muscles contract.
During expiration, the diaphragm and external intercostals relax, shrinking
the volume of the thoracic cavity. This is a passive process, since muscles
relax.
b. Forced breathing- during heavy breathing, accessory muscles are
employed to do two things: i) increase the size of the thoracic cavity more
than usual during inspiration (ex., the pectoralis minor muscles) and ii)
shrink the size of the thoracic cavity even more than usual during
expiration (ex., the abdominals and internal intercostals).
4.Respiratory Volume and Pulmonary Function Tests- terms to know:
Tidal volume, inspiratory reserve volume, expiratory reserve volume, residual
volume, anatomical dead space (understand the meanings, don't memorize the
numbers); I will NOT cover this in lecture, but there will probably be one
multiple choice question on these terms.
C. Gas Exchange in the Body: why different gases within the air (O2 and CO2)
move in different directions, and the directions they move in
1. Properties of gases: Partial pressures- Air that we breathe contains
different kinds of gases. The primary gases in air are N2, O2, CO2, and
H2O (vapor). The gases that we are concerned with are O2 and CO2.
A sample of air contains different concentrations of O2 and CO2.
And the total pressure exerted by air is the sum of the pressures exerted by
each individual type of gas, or their "concentration" in the air. For
instance, a tupperware container full of air might contain 1000 molecules
of O2 and 700 molecules of CO2. In this example, the concentration of O2
is higher than that of CO2, so the pressure exerted by O2 is greater than
that exerted by CO2. The "concentration" of each individual gas in air is
called partial pressure. So, for instance, the partial pressure of O2 in air at
sea level is about 159 mmHg. This is kind of like the concentration of O2
in air at sea level.
What's really important about this is to understand that each
individual gas moves down its OWN pressure gradient. So, we can
consider the movement of O2 and CO2 separately. For instance, O2 will
move from an area with a higher partial pressure ("concentration") of O2
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to a lower partial pressure of O2, regardless of what any other gas in the
air is doing.
2. Gas Exchange between blood, lungs and tissues
a. Pulmonary Gas Exchange (gas exchange between alveoli and
blood) - partial pressure gradients of O2 and CO2:
PO2 (in alveoli) > PO2 (in blood); So, in the lungs, will O2 move into or out of the
blood?
PCO2 (in alveoli) < PCO2 (in blood); So, in the lungs, will CO2 move into or out of the
blood?
Remember that "partial pressure" is just a fancy way of saying
"concentration." Since you understand how solutes move in relation to
their concentrations (diffusion), you can understand how gases move in
relation to their partial pressures.
As deoxygenated blood reaches a capillary lining an alveolus, O2 starts to
diffuse down its partial pressure gradient from the alveolus into the blood.
This happens very quickly; by the time blood gets through the first 3rd of
an alveolar capillary, so much O2 has rushed into the blood that the partial
pressures ("concentration") between air in the alveolus and blood is nearly
equal. Blood has been oxygenated! Remember that as O2 rushes down its
partial pressure gradient into the blood, hemoglobin grabs onto it, and
holds it in the blood.
As deoxygenated blood reaches a capillary lining an alveolus, CO2 starts
to diffuse down its partial pressure gradient from the blood into the
alveolus. This also happens very quickly, within the first 3rd of the
alveolar capillary. Blood has been rid of excess CO2!
Take a minute to draw these processes out. Draw an alveolus and a
capillary next to it. Draw lots of O2 in the alveolus, and just a few in the
first 3rd of the capillary, to indicate that there is a partial pressure gradient.
Draw arrows to indicate the direction O2 moves. Now, draw lots of CO2
in the first 3rd of the capillary, and just a few in the alveolus, and indicate
which direction it will move.
b. Gas exchange in body tissues- I've just described the directions
that O2 and CO2 move between the lungs and blood. This section
describes the directions that O2 and CO2 move between the blood and
tissue cells. Remember, the reason we bring O2 into blood is to deliver it
to tissue cells, which use it to help make ATP (cellular respiration). CO2
is a bi-product of cellular respiration, essentially a waste product, so we
need to move it out to the lungs to get rid of it.
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PO2 (in blood) > PO2 (in tissues); so, will O2 move into or out of tissues?
PCO2 (in blood) < PCO2 (in tissues); so, will CO2 move into or out of tissues?
All cells make ATP constantly. That means, they are constantly using up
O2 and giving off CO2. Really active cells, like leg muscles during a
marathon, or kidney cells in general, use up LOTS of O2 and give up
LOTS of CO2.
As oxygenated blood moves into capillaries of a tissue, O2 rushes down
its partial pressure gradient and enters the cells of that tissue. At the same
time, CO2 rushes down ITS partial gradient and enters the blood. Blood is
now de-oxygenated as it leaves the capillary bed and enters the venule.
Take a minute now to draw THIS process.
D. Transport of Respiratory Gases (O2 and CO2)
1. Oxygen- a tiny percentage of O2 travels in the blood as a dissolved gas.
Most O2 in the blood is carried by hemoglobin (What part, again?)
Several factors can affect how well Hb hangs on to O2. We refer to this
quality, the attraction between Hb and O2, as affinity. Factors that affect
affinity of Hb for O2 are related to cellular activity and include:
-the following information will not be covered or requireda. PO2 itself- when O2 binds to a heme group, the Hb molecule
changes conformation (shape) and causes the other hemes to bind more
O2 really quickly. So, the more O2 is around, the greater the affinity of
Hb. That is, a high PO2 increases Hb affinity. The reverse is true as well;
once an O2 leaves a heme, the rest drop theirs quickly. So, the less O2 is
around, the lowever the affinity of Hb. That is, a low PO2 reduces Hb
affinity.
Where is there a high PO2? So, where does Hb grab onto and hold O2
really well? Where is there a very low PO2? So, where does Hb let go of
O2 really well? Why does this make sense, in terms of where we want O2
to go in the first place?
The O2-Hb dissociation curve depicts this in graph form.
b. PCO2- Increased CO2 reduces Hb-O2 affinity and vice-versa
(how does this relate to cellular activity?)
c. pH- Decreased pH reduces Hb-O2 affinity and vice-versa (how
does this relate to cellular activity?)
d. Temperature- Increased temperature reduces Hb-O2 affinity and
vice-versa (how does this relate to cellular activity?)
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-the following information will be covered and required2. CO2 transport- CO2 travels through the blood in 3 ways:
a. As a dissolved gas ("free floating" CO2)
b. Bound to the protein (not heme) portion of Hb; remember that
increased PCO2 reduces Hb-O2 affinity? Well this is one way: CO2
binding to Hb causes Hb to change conformation and hemes let go of O2
more easily.
This is interesting: Hb affinity for CO2 can be affected, too. Oxygenated
Hb doesn't hang onto CO2 very well, but deO2 (reduced) Hb does. Think about
that. Oxygenated blood comes into a capillary feeding a tissue. Hb is carrying full
capacity of O2, and is hanging on tightly. As it approaches the tissues, it enters an
area with very little O2 and lots of CO2. O2 starts to detach from Hb, as it travels
down its partial pressure gradient into tissue cells.
As the first O2 detaches from Hb, suddenly Hb "loses its love" (affinity)
for its other O2, and "falls in love" (gains affinity) for CO2. The consequence? O2
is very rapidly delivered to tissue cells, and CO2 is very rapidly removed from
tissues.
Related to this, reduced (deO2) Hb also has a greater affinity for H+. We'll
see why this matters in the next section:
c. As bicarbonate (HCO3-) in plasma: most (~70%) CO2 is
transported this way. You may want to review the section in your book on
acids, bases and buffers (ch. 2).
*Some background review info: remember that acids are compounds that release H+
when dropped in water. So, if you took a bunch of dry HCl molecules, they'd probably
look like a powder, and they'd be bound together as HCl. When you drop those molecules
in water, however, most of them would immediately dissociate into H+ and Cl-,
completely separate, not really giving a hoo-ha about what the other is doing.
Strong acids are compounds that tend to dissociate immediately and almost completely.
HCl is a strong acid, so when dropped in water, practically all of the Cl- immediately
drop their H+ s like a hot potato. What this means is that strong acids throw LOTS of H+
into solution. H+ tends to react with other stuff, which gives acidic solutions their
properties.
Weak acids are compounds that tend to dissociate a little bit. H2CO3 (carbonic acid) is a
weak acid, so when dropped in water, only some of the HCO3- drop their H+. In
addition, the otherHCO3- are still on the fence about H+; they will take them back
sometimes to become H2CO3 again. The H+ and anion of a weak acid kind of have an
"on again, off again" relationship. The anions of a weak acid will bind to H+ again, if
there are a lot of H+ around.
Buffers are generally weak acids. Buffers can maintain a solution within a range of pH.
That's because the anions of weak acids will drop their H+ if there aren't many H+ in
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solution, but will bind with H+ if there are lots of H+ in solution. To say that another
way, when H+ concentrations rise, buffers bind them and take them out of solution.
When H+ concentrations fall, buffers release them and put them back into solution.
Buffers, therefore, keep the number of free H+ relatively constant. Since it is the
concentration of free H+ in solution that determine acidity, buffers keep pH relatively
constant.
End of background*
As CO2 enters the blood, the enzyme carbonic anhydrase in RBCs carries
out the following reaction:
CO2 + H2O --> H2CO3 (carbonic acid)
Carbonic acid releases H+, forming H+ and HCO3-.
As blood enters the lungs, carbonic anhydrase drives the following
reaction:
H2CO3 --> CO2 + H2O, and the CO2 diffuses into the lungs.
What happens to the H+ and HCO3- in the mean time? Well, H+ gets kind of a sheltered
ride to the lungs. As soon as H2CO3 releases a H+, Hb grabs it and doesn't let go until it
gets to the lungs. Boring ride, poor H+. (Remember, from b above, that deoxygenated Hb
has a greater affinity for H+; why does this make sense?)
HCO3-, on the other hand, gets released into the plasma, and galavants with all sorts of
other H+ as it acts as a buffer on its way to the lungs. What a slut.
In the lungs, the HCO3- and H+ recombine to H2CO3, which is converted to CO2 and
H2O (by which enzyme?). The CO2 diffuses into alveoli, and we breathe it out.
The Chloride Shift- In tissues, the reaction CO2 + H2O --> H2CO3 --> HCO3- + H+
occurs inside Red Blood Cells. H+ stays inside the cell (where?) and HCO3- leaves the
cell. There are tons of HCO3- leaving a RBC as it passes through tissues, picking up
CO2. That kind of mass movement of anions could cause a serious change in potential,
which would affect the cell's function. (Remember the electricity of neurons and muscle
cells is caused by the mass influx/efflux of ions).
To counter a change in potential caused by mass exodus of HCO3- anions, the cell takes
in a Cl- for every HCO3- it ejects, so that there is no net change in charge. This
phenomenon is called the Chloride Shift, and we'll see it again in later chapters.
E. Control of Respiration1. Local control: Ventilation-Perfusion coupling- the quick and
dirty explanation: arterioles serving specific alveolar sacs will constrict or
dilate to shunt bloodflow to the most prosperous areas. In addition,
bronchioles will dilate to overcome problems with airflow to specific
alveolar sacs. These arterial and bronchial responses are based on O2 and
CO2 levels, respectively. This phenomenon allows O2 pickup to be
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maximized, and allows second-by second changes in blood flow and air
flow.
2. Neural control- The basic breathing rhythm is set by centers in the
medulla and pons that interact with one another. The centers in the pons have
direct control over the centers in the medulla, and the centers in the medulla have
direct control over the breathing muscles. The primary breathing rhythm center in
the medulla that controls restful breathing is the Dorsal Respiratory Group.
Breathing rate and depth can be affected by several factors, I'll focus on O2 and
CO2.
a. O2- chemoreceptors in the carotid and aortic bodies monitor O2 levels.
When O2 levels drop, how is breathing rate and depth affected?
b. CO2- the most influential factor on breathing rate and depth. CO2 from
the blood diffuses freely into the CerebroSpinal Fluid via the choroid plexuses.
Recall that the medulla abuts the fourth ventricle. The medulla contains
chemoreceptors that are sensitive to H+. In the CSF, some CO2 is converted to
HCO3- + H+. As CO2 levels rise, more H+ is released and binds to
chemoreceptors in the medulla. When CO2 levels rise, how is breathing rate and
depth affected?
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