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Physiology 6051, Spring, 2008
RESPIRATORY PHYSIOLOGY LECTURES AND READINGS
Douglas Wangensteen, Ph.D.
6-125 Jackson Hall
(612) 625-5580
E-mail: [email protected]
In this section of the course your main source of information will be Chapter 13 in your textbook:
Human Physiology, 11th Ed., by Widmaier, Raff & Strang. This entire chapter is assigned reading;
it should be your major source of information about respiratory physiology. Please read, or at
least skim, the appropriate sections of the text (see below) before each lecture. The purpose of the
lectures is to help solidify the important concepts in your minds and give you a framework upon which
to build a more complete understanding of how the respiratory system works. Most of the material in
the chapter will also be presented in lecture, but not in the detail found in the text. The “Summary” at
the end of Chapter 13 outlines important concepts and is an excellent study guide. You should
understand the statements in this outline. I will refer to this outline as I make up exam questions.
Exam questions for this section of the course will primarily (at least 75%) come from the text.
Only about 25% of the exam questions will come from lecture material that is not in the text. You can
get an idea of the kinds of questions I ask by looking at previous exams. I also suggest that you work
through the Test Questions and Thought Questions at the end of Chapter 13. Questions like this will
appear on the exam.
Lecture Topics and Related Readings
3/5:
3/7:
3/10:
3/12:
3/14:
Lung structure, events in breathing, resistances to breathing (pp. 442-452)
[pp. 477-488 in the 10th Edition]
Airways resistance and lung elastic recoil (pp. 452-455)
[pp. 488-492 in the 10th Edition]
Total ventilation and alveolar ventilation, transport of oxygen and carbon
dioxide by blood (pp. 456-460, 463-469)
[pp. 492-498, 500-507 in the 10th Edition]
Gas exchange within the lungs (pp. 460-462, 476-478)
[pp. 498-500, 514-516 in the 10th Edition]
Control of breathing (pp. 409-476, 477-478)
[pp. 507-514, 516 in the 10th Edition]
Laboratory/Demonstration Session
The subject of the respiratory physiology lab/demo on 3/13 will be pulmonary function testing.
The lab will begin with a discussion of how pulmonary function is measured clinically and
then everyone will make lung function measurements on themselves.
ON THE FOLLOWING PAGES ARE OUTLINES OF THE MAIN POINTS FOR EACH
LECTURE TOPIC AND SOME RELEVANT LUNG DISEASE EXAMPLES.
1
Lecture 1: Lung Structure, Events in Breathing, Resistances to Breathing
The primary function of the lungs is to change venous blood into arterial blood by adding O2 and
removing CO2 from the venous blood that enters the lungs from the right ventricle. Physicians
determine how well the lungs are accomplishing this task by measuring the partial pressures of
O2 and CO2 in arterial blood. (See Fig 13-21.)
The basic design of the lungs is to bring inhaled air and venous blood in very close proximity,
separated by a very thin barrier with a very large surface area. This allows O2 and CO2 to move
into and out of blood by diffusion. The principal elements of the design are (Figs 13-1 & 13-3):
 Branching airways bring air from the atmosphere into small sacs called alveoli that are 100200 m (0.1-0.2 mm) in diameter.
 Branching blood vessels bring venous blood from the right ventricle into capillaries that
form a meshwork around each alveolus.
 Blood in capillaries is separated from gas in alveoli by a cellular “blood-gas barrier” that is
only about 0.1 m thick and has a total surface area of about 100 m2.
How People Breathe
Ventilation is cyclic: inhalation . . . exhalation . . . etc. In a healthy person at rest:
 Tidal Volume (VT) is about 500 ml.
 Breathing Frequency (f) is about 15 breaths/min.
 Inhalation requires energy: muscle contraction.
 Exhalation is passive.
The way inhalation and exhalation occur is shown in Fig 13-13. Study and understand this figure!
This is a diagram of the lung-chest wall-diaphragm system:
The lungs are elastic structures that increase in volume
when the pressure inside the lungs (Palv) becomes greater
than the pressure outside the lungs (Pip). The lung volume
is proportional to the difference in pressure between inside
and outside (Palv – Pip), which is called the
transpulmonary pressure or Ptp.
2
Figure 13-13
Points to remember from Fig. 13-13:

When we inhale, inspiratory muscles cause the intrapleural pressure (Pip) to decrease. This
makes the transpulmonary pressure (Ptp = Palv – Pip) increase, which causes lung volume to
increase.

The larger Ptp becomes, the larger the lung volume becomes.

Intrapleural pressure (Pip) is always less than atmospheric (“negative pressure”).

Flow into or out of the alveoli occurs because the alveolar pressure (Palv) is different than
atmospheric.

Alveolar pressure (Palv) is atmospheric (zero) at the end of inhalation and the end of
exhalation, but is >0 during exhalation and <0 during inhalation.
3
Work of Breathing
Pressures generated by the inspiratory muscles are relatively small (just a few mm Hg), so the
metabolic cost of breathing is small. For a healthy person at rest, only 2-3% of the total O2
consumption is due to activity of the respiratory muscles, whereas the work of the heart accounts
for about 10%.
However, lung diseases can cause the work of breathing to increase by increasing the forces that
respiratory muscles must work against. The inspiratory muscles work against two opposing forces:
Lung Elastic Recoil (70% of the work of breathing in a healthy person at rest)
Airways Resistance (30 % of the work of breathing in a healthy person at rest)
Restrictive lung diseases cause lung elastic recoil to increase.
Examples: lung fibrosis, histoplasmosis, neonatal respiratory distress syndrome
Obstructive lung diseases cause airways resistance to increase.
Examples: asthma, emphysema, cystic fibrosis
The purpose of the lab/demo on Thursday, 3/13 is to help you understand how tests of pulmonary
function can show whether a lung disease is restrictive, obstructive or a combination of the two.
4
Lecture 2: Airways Resistance and Lung Elastic Recoil
Airways Resistance and Obstructive Lung Disease
Case #1
A 17 year-old student has had frequent episodes of wheezing, coughing and shortness of breath
since having pneumonia when he was two years old. In the past year these attacks have been more
severe at night, and occasionally he must sleep in a chair. When he was studied in the pulmonary
function laboratory he had no dyspnea or cyanosis. A chest X-ray showed slight over-inflation of
the lungs and no evidence of localized disease.
Pulmonary function test results:
Actual
Predicted Post-Bronchodilator
Vital Capacity, VC [liters]
2.8
4.8
3.7
Residual Volume, RV [liters]
3.5
1.2
2.6
Total Lung Capacity, TLC [liters]
6.3
6.0
6.3
FEV1/VC [%]
45%
>80%
60%
Airways resistance (Raw) is the opposing force encountered by gas flowing through the lung
airways. This is analogous to the resistance to blood flow through arteries and veins and the same
principles apply (eqs. 13-1 & 13-2, p. 446):
Flow = (Driving Force)/(Resistance) = P/R = (Palv – Patm)/ Raw
Important points:

Raw depends upon the type of flow (laminar vs. turbulent) and the gas being breathed (e.g.
air vs. helium), but most importantly, as in the cardiovascular system: R  (radius)-4.

Airway radius is under both neural and humoral control.

Airway radius increases as lung volume increases, and vice versa.

In obstructive diseases, airway radius is decreased.
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Lung Elastic Recoil and Restrictive Lung Disease
Case #2
A 32 year-old high school teacher previously in good health noted the onset of dyspnea during
exertion about six months ago. The condition has progressively worsened, to the extent that her
classroom has been moved to the first floor of the building. For the past two months she has had a
non-productive cough that has progressively become severe enough to cause sleep disruption. She
has never smoked, has no pets, and has not traveled outside of Minnesota and Wisconsin for
several years. At a recent examination, her blood pressure, pulse and temperature were normal and
her respiratory rate was 25/min. Pulmonary function test results were as follows:
Actual
% Predicted
Vital Capacity, VC [liters]
2.4
44%
Total Lung Capacity, TLC [liters]
3.1
41%
FEV1 [liters]
2.0
45%
FEV1/VC [%]
83%
>80%
Elastic recoil is the force exerted by the lungs to resist inflation. “Stiff” lungs have increased
elastic recoil and therefore require more force to inflate them. Lung elastic recoil is determined by
measuring the transpulmonary pressure needed to inflate the lungs to a given volume. The
resulting “pressure-volume” (P-V) curve describes the lung’s elastic properties (Fig 13-16).
Lung compliance (CL) = (Lung Volume)/(Transpulmonary Pressure) – see eq. 13-4. It is the
slope of the P-V curve at any point. By convention, CL is taken to be the slope of the P-V curve at
the volume at the end of a normal exhalation.
Important points:
 When lung compliance is reduced, lung elastic recoil is increased, and vice versa.

In restrictive diseases, lung compliance is decreased.

Lung elastic recoil is determined by tissue forces and surface tension forces.

Tissue forces are due to elastin and collagen fibers within the lung. In lung fibrosis there is
an increase in these fibers and the lung becomes stiffer (CL decreases).

Surface tension forces occur at the thin liquid film that lines every alveolus. Alveolar
surfactant keeps surface tension forces very low, so the lungs are easy to inflate. In
respiratory distress syndrome of the newborn, the amount of alveolar surfactant is reduced
so CL is decreased.
6
Lung Volumes to Remember
Fig 13-18 gives many lung volumes and capacities. Here are the ones you should remember:
Total Lung Capacity (TLC) = The volume of gas in the lungs after a maximum inhalation.
Residual Volume (RV) = The volume of gas remaining in the lungs after a maximum exhalation.
Functional Residual Capacity (FRC) = The volume of gas in the lungs at the end of a normal
exhalation.
Vital Capacity (VC) = The difference between TLC and RV. The volume exhaled after taking a
maximal inhalation and then slowly exhaling as much as possible.
In the lab/demo this volume will be referred to as:
Forced Vital Capacity (FVC) = The total volume exhaled after taking a maximal
inhalation and then exhaling to RV as rapidly as possible.
There is one more volume, not shown in the figure but mentioned on p. 455:
Forced Expiratory Volume in 1 sec. (FEV1) = The volume exhaled in 1 second after inhaling to
TLC and then exhaling to RV as fast as possible.
You will be measuring your FVC and FEV1 in the lab/demo session on 3/13.
7
Lecture 3: Total Ventilation and Alveolar Ventilation, Transport of Oxygen and Carbon
Dioxide by Blood
Case #3
A 68 year-old man was brought to the Emergency Department by his wife and daughter. He is
dyspneic, cyanotic, confused, disoriented and lethargic. His wife said he was diagnosed with
chronic obstructive pulmonary disease (COPD) ten years ago. He was doing as well as could be
expected until two days ago, when he said he thought he was “getting the flu”. An arterial blood
sample was taken and the results were:
PO2 = 45 mm Hg
PCO2 = 70 mm Hg
He was given oxygen to breathe and admitted to the hospital. His condition improved and he was
discharged several days later.
Two weeks later the man is resting at home. He is feeling better and his COPD symptoms are
stable. He is breathing room air. If someone were to take an arterial blood sample while he was
seated in his favorite chair the results would be:
PO2 = 75 mm Hg
PCO2 = 40 mm Hg
Total Ventilation, Alveolar Ventilation and Gas Exchange
The most important function of the lungs is to make arterial blood with PO2 and PCO2 values within
normal limits (see Fig. 13-21). Ventilation plays an important role in this process. Bottom line:
Alveolar ventilation, relative to the body’s metabolism and considering the composition of the
inspired air, determines arterial blood PO2 and PCO2.
The volume of air we breathe out from our mouth or nose per minute is called the (eq. 13-6)
Minute Ventilation: VE  f  VT
However, not all the air we breathe in through our mouth or nose reaches the alveoli. The volume
that stays in the airways does not participate in gas exchange and is called the Dead Space Volume
(VD). As an approximation for all but the very thin or obese: VD (ml) = Weight (lbs).
The volume of air that enters or leaves alveoli per minute is called the (eq. 13-7)
Alveolar Ventilation: VA  f VT  VD 
Alveolar ventilation determines the alveolar PO2 and PCO2 because this is the ventilation that
reaches the alveoli. The relationship between VA and alveolar PO2 and PCO2 is given by the
following equations, which are the basis for the curves shown in Fig. 13-22:
PACO 2  PB  47 
VCO 2
VA
PAO2  PIO 2  PB  47 
8
VO 2
VA
Important points:

The alveolar PO2 and PCO2 determine the arterial PO2 and PCO2. The respiratory control
system tries to maintain arterial PO2 = 90-100 mm Hg and arterial PCO2 = 40 mm Hg. To
accomplish that, VA changes to match VO 2 and VCO 2 as people change their activity levels
throughout the day.

If a person’s activity level is constant:
when VA increases arterial PO2 increases and PCO2 decreases.
when VA decreases arterial PO2 decreases and PCO2 increases.

A person is hyperventilating if the arterial PCO2 is less than 40 mm Hg.

A person is hypoventilating if the arterial PCO2 is more than 40 mm Hg.
Transport of O2 by Blood
O2 is carried in blood in two forms: dissolved and bound to hemoglobin (Hb). The presence of Hb
in blood markedly increases the ability of blood to carry O2 (see Table 13-8).
As the PO2 of blood increases the amount of O2 being carried by blood and the % saturation of Hb
increase, but the relationship is curvilinear (see Fig. 13-26, the O2-Hb dissociation curve).
 The % saturation of Hb (% sat) is a measure of how many of the O2 binding sites on all
the Hb in blood are filled: % sat = 100 x (amount of O2 bound to Hb) / (total amount of
O2 that could be bound to Hb).
 When PO2 = 100 mm Hg about 98% of the O2 binding sites on Hb are filled (98%
saturation), so increasing the PO2 will not significantly increase the % saturation or the
amount of O2 in blood.
 The % sat in venous blood returning to the lungs (PO2 = 40) is about 75%.
 The O2-Hb dissociation curve changes when the temperature and pH of blood changes: see
Fig. 13-29.
Carbon monoxide binds to the O2 binding sites on Hb molecules much more strongly than does
O2. This reduces the number of O2 molecules that can be carried by Hb and also causes those O2
molecules that are bound to Hb to be bound much more tightly. The net effect is that less O2 is
carried to metabolizing tissues.
9
Transport of CO2 by Blood
CO2 is carried by blood in three forms. In arterial blood, 6% is dissolved, 6% is bound to Hb and
other proteins (in a different way than O2), and 88% is HCO3- in plasma. (The figures given in the
text are correct, but they indicate how CO2 entering blood at the tissues is distributed among these
three forms.)
Fig. 13-30 is very important; it describes the steps involved in CO2 movement into blood in tissues
and out of blood in the lungs. Here are some key points to remember about the steps involved
when CO2 enters blood in tissue capillaries:

CO2 diffuses into red blood cells where it combines with H2O to form carbonic acid. This
happens in red blood cells because the enzyme carbonic anhydrase is present there.

Carbonic acid dissociates into H+ and HCO3-, and the HCO3- is moved from the red blood
cell into plasma by a membrane transporter that exchanges HCO3- in the red blood cell for
Cl- in plasma.

CO2 binds with the amino groups of Hb and other proteins. It does not bind to Hb in the
same way as O2.
The opposite steps occur in the lungs, where CO2 leaves blood.
10
Lecture 4: Gas Exchange within the Lungs
This lecture will focus on the transport of O2 within the lungs, especially how O2 transport is
disrupted in people with lung disease. We will refer again to Case #3.
As venous blood passes through the lungs it is changed to arterial blood. In a person with healthy
lungs arterial blood has PO2 = 90-100 mm Hg and PCO2 = 40 mm Hg. In many lung diseases,
arterial PCO2 does not change, but arterial PO2 is reduced. Table 13-11 lists four potential causes of
reduced arterial PO2: hypoventilation, diffusion impairment, shunt and ventilation-perfusion
mismatching. Here are some key points:

Hypoventilation occurs when alveolar ventilation ( VA ) is reduced for some reason.
Arterial PCO2 also increases. This was presented in Lecture 3.

Diffusion of O2 from alveolar gas into capillary blood is very fast (see Fig. 13-23).
Therefore, diffusion impairment occurs only rarely in lung disease.

A shunt is a situation where blood flows through the lungs but does not flow past alveoli
that are ventilated. The alveoli may be filled with fluid (pulmonary edema) or with
inflammatory cells and exudate (pneumonia). This is a serious problem because blood
flowing through the shunt remains venous blood (PO2 = 40) and mixes with the blood that
has flowed through healthy parts of the lungs. The result is a decrease in arterial PO2.

For the lungs to function most efficiently every region of the lungs should receive equal
amounts of alveolar ventilation ( VA ) and blood flow ( Q ). Ventilation-perfusion
mismatching (the book calls it ventilation-perfusion inequality) is the most common cause
of reduced arterial PO2. It occurs, for example, when because of disease the VA to a part of
the lung is reduced but not completely blocked and Q is unchanged. This will cause the
PO2 in the blood leaving that part of the lung to be decreased and, therefore, the arterial PO2
will be decreased. This happens because lung diseases generally affect one part of a
person’s lungs more than another. The lungs compensate somewhat for ventilationperfusion mismatching by reflexes that change local ventilation or blood flow.
(continued)
11

Even in young, healthy people VA and Q are not equal throughout the lungs. This is
because of anatomical differences from one region to another and because the lungs are
large so both VA and Q are affected by gravity. In a young, healthy person the arterial PO2
is about 5 mm Hg lower than if VA and Q were uniformly distributed within the lungs.
12
Lecture 5: Control of Breathing
An Example: Breathing at High Altitude
Five subjects went from sea level to the top of Pike’s Peak, an altitude of 14,110 ft:
PB = 445 mm Hg, PIO2 = 84 mm Hg (like 12% O2 at sea level)
Their alveolar ventilation and arterial blood PO2 and PCO2 were measured during a two week stay:
VA [liters/min]
Sea Level
8.2
2 days
10.5
5 days
11.5
14 days
11.5
PAO2 [mm Hg]
95
43
50
50
PACO2 [mm Hg]
38
25
20
20
Why does it take five days for the alveolar ventilation to increase to its final level?
The respiratory control system is responsible for keeping the arterial PO2 and PCO2 within relatively
narrow limits. It is an example of a feedback control system with the following components:
The respiratory muscles are skeletal muscles that do not have intrinsic pacemakers; they only
contract when stimulated by motor nerves. The nerves originate in the respiratory control centers.
The respiratory control centers are in the brain stem. Exactly how these centers generate a cyclic
breathing pattern is not understood. There are regions that are active during inhalation, regions
active during exhalation, and there may be pacemaker cells, but that is still controversial. These
centers receive input from several places, including:
 the cerebral cortex (we can hold our breath)
 chemoreceptors
 receptors within the lungs, such as stretch receptors, irritant receptors, j-receptors
13
The chemoreceptors monitor arterial PO2 and PCO2. There are two types:

Central chemoreceptors are located in the brain. They monitor [H+] (but not PO2) in brain
tissue. Measuring brain [H+] is a surrogate for measuring arterial PCO2. These receptors are
the most important for sending information about PCO2 to the respiratory control centers.

Peripheral chemoreceptors are located in the carotid and aortic bodies. They monitor PO2
and [H+] in arterial blood. The carotid bodies are the more important of the two.

By monitoring [H+] the chemoreceptors also monitor PCO2. This is because as PCO2
increases H+ also increases due to the following chemical reaction:
CO2  H 2O  H 2 CO3  H   HCO3

The respiratory control system is very sensitive to changes in arterial PCO2 (see Fig. 13-36).
Arterial PCO2 is controlled within narrow limits.
The respiratory control system is less sensitive to decreases in arterial PO2 (see Fig. 13-34).
Ventilation is not stimulated to increase until arterial PO2 falls to below 60-70 mm Hg.
The respiratory control system is also very sensitive to changes in arterial pH (see Fig. 13-38).
Considering all this information, why does it take five days for the alveolar ventilation to
increase to its final level when a person goes to Pike’s Peak?
14