The Respiratory System

Supplement to Text, Chapter 9

RTT 100
Professor Michael Nazzaro
Supplement to Text, Chapter 9
The Respiratory System
You must study BOTH the chapter
and this supplement

Section 1
Development of the Respiratory System

Reference, Text pg. 150-164

1
 Respiratory System Development: Overview
The lungs do not function as breathing organs during intrauterine life but they must be sufficiently developed so
they can immediately perform ventilation and gas exchange within seconds after birth. At birth, the human
pulmonary system makes a remarkable transition from a fluid filled non-gas exchange structure to the fluid
lined gas exchange structure it will remain.
• In the embryonic period (the first 6 to 8 weeks), all the body’s major organs begin to develop from the three
primary (germ) layers: the ectoderm, the mesoderm, and the endoderm.
• Pulmonary system development begins at about 3 weeks after conception, in the embryonic period, and
continues through the fetal period up to birth. Lung growth continues after birth into the eighth or tenth year
of life.
− Genetic dysregulation during this phase can lead to a number of serious, possibly fatal conditions.
• The stages of lung development as shown in Fig. 9-1 & Table 9-1 are generally correct, but there is certainly
overlap as the minor conflict between the text on pg. 159 and the numbers in Table 9-2 demonstrates.
• The Carnegie stages are a system that embryologists use to describe the apparent maturity of the embryo
during the first 8 week (56 day) period after conception.
– The 23 Carnegie stages are based on the appearance of the embryo’s external physical features.
• The fetal period covers the remaining 32 weeks of gestation
– The organs that began to form during the embryonic period continue to grow and begin to differentiate
(a process called organogenesis) during the fetal period.
– Pulmonary development during the fetal period occurs in four stages, named:
• Pseudoglandular, Canalicular, Saccular (aka terminal saccular), and Alveolar stages.
• The fetal pulmonary epithelium produces fetal lung liquid (about 15 ml per kg of body weight each day.
• Fetal lung liquid distends the alveoli; alveolar distension and is essential for normal lung growth.
– The fetal lung fluid flows through the airways and into the mouth where some of it is swallowed and some
is expelled into the amniotic fluid.
–Breathing movements (chest expansion and contraction), controlled by a breathing center in the brain
stem, begin around the end of the embryonic period.
• By about the 25th week of fetal growth, the pulmonary capillaries develop and alveolar Type II pneumocytes
are mature enough to begin producing pulmonary surfactant.
– A baby born prior to 37 weeks gestation is classified as premature.
– 24-26 weeks is usually considered the earliest point at which a fetus will be viable (able to survive) in
the extrauterine environment with medical and respiratory support.
Reference: Note, Text pg. 159-164 2
 Fetal Lung Development: Pseudoglandular Stage
The pseudoglandular stage runs from about the 6th or
7th to the 16th week of the fetal period.
• In this stage the developing lung resembles a
hollow tube-like (glandular) structure surrounded by
mesenchymal cells, hence its name.
• The primitive bronchial tree is initially lined with
cuboidal epithelial cells.
• These cells will differentiate into the ciliated
epithelium and the mucus secreting goblet cells.
–The first ciliated epithelial cells can be found by
the 8th to 13th week of pregnancy.
• The first type II pneumocytes (actual alveolar cells)
are seen lining the areas that will become the
parenchymal (respiratory or gas exchange) part of
the lung.
• Irregular dichotomous branching continues and all
airway divisions (not generations) are essentially
complete by 16 weeks of gestation.
• Terminal bronchioles (the most distal branches)
begin to differentiate to form respiratory
bronchioles and alveolar ducts.
• Cartilage begins to form around the larger airways
and smooth muscle forms around both airways and Note the following characteristics:
major blood vessels. • The small size of the potential air spaces (alveoli)
• At this stage, the developing broncho-pulmonary shown in white.
epithelium also begins to produce fetal lung liquid. • The thickness of the mesenchymal material that
–Fetal lung liquid is essential to normal pulmonary will become the alveolar septa (the pink areas
development. between the white alveoli).
–Some of the liquid is expelled from the mouth • The distance of the capillaries from the alveoli.
and becomes part of the amniotic fluid. • The absence of alveolar Type I pneumocytes.
These lungs are not capable of extrauterine
survival.
Reference: Note, Text, pg. 160, 164 (Fig. 9-4A).
3
 Fetal Lung Development: Canalicular Stage
The canalicular stage from the 16th to the 24th or 26th
week of the fetal period.
• Canaliculi (canals) begin to branch out from the terminal
bronchioles
– The canaliculi will develop into the actual respiratory
(gas exchange or parenchymal) tissue of the lungs.
• All the alveoli that develop from a single terminal
bronchiole form a parenchymal unit called an acinus
(aka terminal respiratory unit).
– Each acinus consists of the respiratory
bronchioles, alveolar ducts and (after further
development) the alveolar sacs that branch from
a single terminal bronchiole.
• The chief characteristic of this phase is the alteration of
the epithelium and the mesenchyma that surrounds the
air spaces.
• Capillaries begin to invade the mesenchyma along the
acinus.
– The capillaries will eventually surround the acini
in a dense layer and will make gas exchange
possible.
• The lumena (open diameter) of the canals become wider
and the epithelial cells begin to get flatter.
– The cuboidal Type II pneumocytes are the cells that
develop into the flattened Type I pneumocytes. Note the following characteristics:
• Some of the Type II alveolar pneumocytes have
• By the 24th week of pregnancy enough type II differentiated into the flatter Type I pneumocytes
pneumocytes have differentiated into the type I that will form the alveolar/capillary (A/C)
pneumocytes, and enough capillaries have proliferated membrane.
into the mesenchyma to allow the fetus to survive • Alveolar septa are getting thinner.
outside the uterus with supplemental oxygen, support of • Capillaries are beginning to surround the
ventilation, and surfactant administration. developing alveolar sacs.
Reference: Note, Text, pg. 163 (Fig. 9-4 B). 4
 Fetal Lung Development: Saccular Stage
This stage is also called the terminal saccular stage. It progresses from about 26 weeks to birth.
• The most peripheral air spaces now have a saclike appearance, hence the name.
• The most important changes during this period are:
– The sacs distal to the terminal bronchioles begin to get longer and wider.
– The final generation of sacs; the ones that will become alveoli, is formed.
– The interstitial material becomes further compressed decreasing the distance between the capillary blood and the alveolar air.
• Alveoli start to separate as thin mesenchymal ridges begin to form the septa (green dots).between the sacs.
• Type I and Type II pneumocytes continue to differentiate and Type I cells become the most abundant epithelial cells in the
lung.
– The flattened Type I cells make up the largest number of Type I pneumocytes.
– The Type II cells develop a rounded shape and have more lamellar bodies that make and store pulmonary surfactant.
– Surfactant has a half life of about 14 hours, so it has to be continuously synthesized by the Type II pneumocytes.
– Type II pneumocytes also appear able to differentiate into Type I cells to help repair lung injury.

A (arrows) Smooth muscle cell precursors,

elastic fibers, and collagen fibrils accumulate
in the immature alveolar septa at sites where
new septa will be formed (green dots).
B: As the new septa grow, 1 of the 2 layers of
the capillary network of the preexisting septa
begin to fold up (red ovals at the green dots)..
C: As the septa folds up it begins to subdivide
the preexisting air spaces, and new alveoli are
created. The preexisting and the newly formed
septa still contain a double-layered capillary
(microvascular) network.
D: The next phase of microvascular maturation
can take from 0 to 3 years. During this phase Note: The red
the capillary layers fuse and form a central ovals are
capillary layer surrounding the alveoli. capillaries, NOT
red blood cells

Reference: Note, Text, pg. 163-5 (Fig. 9-4 C). 5

 Fetal Lung Development: Alveolar Stage
The text says the alveolar stage begins at about the 32nd
gestational week, but the actual starting point is not sharply
defined. Some alveoli probably develop at the end of the
terminal saccular stage. Alveolar development continues into
the 8th or 10th year of life.
• Formation of the hexagonal shaped alveoli (alveoli are not
spherical) is closely linked to the deposition of the structural
protein elastin in the terminal sacs.
• Terminal saccules become invaginated (enclosed in a sheath
of tissue) by epithelial cells protruding from the sac wall.
–The epithelial cells form crests (Slide 5) which develop into
the alveolar septa that separate individual alveoli. The
separation greatly increase the surface area for gas
exchange.
• The alveolar epithelium and the capillary endothelium rest on
top of basement membranes which are fused to virtually
form a single structure.
–This arrangement makes the alveolar/capillary “barrier” to
gas exchange extremely thin (< 0.5 micron) and gas
exchange extremely efficient.
• Most authors agree that a full term neonate (new born) has
about 50 million alveoli.
–This number of alveoli provide a gas exchange surface
area of about 3 to 4 m2.
• Post natal lung growth is geometric, but the number of
airways does not increase.
• The number of alveoli reach the adult number of about 300
million by two years of age.
–The text uses cites a range of 270 to 790 with 480 million
by age 8 to 10.
• Whatever the actual number of alveoli, the adult lung has a
gas exchange surface area between 50 and 100 m2.

Reference: Text, pg. 163 (Fig. 9-4 D). 6

Fetal Lung Development: Fetal Circulation
• In the uterus (in utero) the fetus does
not use the lungs to breathe.
• In addition, the liver is not fully
developed.
• Also, fetal blood has relatively low
oxygen:
• Fetal Hemoglobin Saturation (SaO2)
is only 70-80%).
• The fetal circulation maximize
oxygenation of the brain, the heart,
and other vital organs by largely
bypassing the lungs and liver.
• The fetal cardiovascular system uses
three shunts for the bypass:
1. The ductus venosus (DV):
• Shunts ≈ 50% of the left umbilical
vein blood past the liver into the
inferior vena cava (IVC).
2. The foramen ovale (FO):
• Diverts blood from the right atrium
to the left atrium.
3. The ductus arteriosus (DA):
• Diverts blood from the
pulmonary artery to the
descending aorta.

Reference: Note, Slide 2 & Note, Text, pg. 166 (Fig. 9-7D). 7
 Pulmonary Development: Respiratory Events at Birth
Before birth the fetus's gas exchange organ is the mother’s placenta. At birth the fetus makes the
transition to a neonate breathing air. A number of events occur at that transition:
• Several days before birth the fetal lung epithelium stops producing fluid.
– The fluid begins to be reabsorbed by the fetal pulmonary capillaries.
– During vaginal delivery about one third of the remaining fetal lung liquid is squeezed out of
the lungs by compression of the thorax during passage through the birth canal.
• The first breath which starts the process of establishing lung air volumes is initiated by central
neurologic stimulation secondary to arousal by:
– Sound, light, temperature changes, and touch associated with delivery.
– Central chemoreceptor cells in the medulla signal the respiratory muscles to work in
response to receptor stimulation by acidemia and hypercarbia (high CO2 in the blood).
– Peripheral chemoreceptor cells located in the aorta and carotid arteries respond to arterial
hypoxemia (low O2 in the blood).
• The baby must generate very high negative inspiratory pressures during the first few breaths to
overcome:
– High airway resistance due to the remaining viscous fluid in the airways.
– High inertia of the viscous fluid in the airways.
– High alveolar surface tension because of the remaining fetal lung liquid in the alveoli.
• As the baby exerts muscle strength to distend the alveoli the adrenal gland is stimulated to
release the hormones cortisol and epinephrine.
– Cortisol is a stress hormone that increases blood sugar through gluconeogenesis.
• This provides glucose for ATP production.
– Epinephrine produces a number of responses, including airway dilation which reduces
airway resistance.
• Alveolar distension also stimulates the Type II pneumocytes to produce pulmonary surfactant
which helps reduce surface tension.
Reference: Note, Text pg. 164-65, (Fig 9-5), 691-93. 8
Cardiopulmonary Anatomy &
Physiology
RTT 100
Professor Michael Nazzaro
Supplement to Text, Chapter 9
The Respiratory System
You must study BOTH the chapter
and this supplement

Section 2
The Adult Respiratory System
Reference, Text pg. 171-207
9
 The Adult Respiratory System: Introduction
• The primary function of the respiratory system is the continuous exchange of gases between
the body cells and the atmosphere by the processes of ventilation, gas exchange, and
transport.
– Carbon dioxide (CO2) is continually produced by the cells of the body and must be
continuously removed and excreted into the atmosphere.
– Body cells also need a continuous supply of oxygen (O2) which must be absorbed from
the atmosphere.
– Both CO2 and O2 are transported to and from the lungs by the blood.
• It has been estimated that over a normal 75 year lifespan the respiratory system will
move 250 million liters of air in and out of the lungs and the cardiovascular system will
pump 250 million liters of blood to and from the lungs.
• Inhaled air must also be warmed to body temperature, humidified to the point of saturation,
and filtered before it reaches the alveoli.
• Once in the lungs, the air in the alveoli and the blood in the pulmonary capillaries has to be
equally matched on either side of the extremely thin alveolar/capillary (A/C) membrane (V/Q
matching).
• The respiratory system must be able to adapt to the changing levels of CO2 production and
O2 consumption that the body faces at rest and during exercise.
• Finally, this tremendous amount of work has to be performed continuously, automatically and
with the lowest expenditure of energy.
• Many texts now use the term External Respiration to describe the process of breathing which
includes the processes of ventilation, gas exchange and gas transport.
• The term respiration (aka internal respiration) properly refers to the metabolic processes that
mitochondria in the cells use to obtain energy by oxidizing glucose to produce ATP.
• The mechanical process of moving air into and out of the alveoli is usually called breathing or
ventilation.
Reference: Note, Text pg. 159, 171, 414-16 (Fig. 20-10), 821. 10
Adult Thorax: Anterior & Posterior Bony Landmarks
Thoracic Inlet
(the operculum)

(Angle of Louis)

Anterior and Posterior Diagrams of the

Anterior-Posterior (AP) Chest X-Ray (CXR) Chest

•The imaginary lines correlate well with the bony surface landmarks of the anterior and posterior thorax.
•The central anterior thoracic landmark, the sternum, is made of three fused bones:
–the manubrium, the body (gladiolus), and the xiphoid process.
•The xiphoid is the smallest of the three bones.
– It provides an attachment point for attachment of some of the abdominal muscles.
– During chest compressions in cardiopulmonary resuscitation (CPR) the xiphoid process can be fractured
and damage underlying organs.
Reference: Note, Text pg. 174 (Fig 9-18), 175 (Fig.9-20), 181, 432 (Fig. 21-2). 11
•
Adult Thorax: Rib Structure & Articulation
The 12 pair of ribs are elastic (flexible) arches of bone, but some people may have one more or one less..
• The joints of the thoracic cage bones allow the thorax to change its anteroposterior and lateral dimensions during breathing.
• Intervertebral joints and disks give the spinal column a degree of flexibility without reducing its stability.
• Costovertebral joints allow the heads of ribs 2 through 9 to articulate with the costal articular facets of the vertebra above and
the one below. The costovertebral joints of ribs 1, 10, 11, and 12 articulate with only one facet on the adjacent vertebra (rib 1
with the articular facet on T1, etc.), and differ in other ways which is why they are called atypical ribs.
• Costotransverse joints allow the tubercle of the rib to articulate with the articular facet on the transverse process of the adjacent
vertebra.
• Costochondral joints exist because the distal end of the ribs are connected to the sternum by a flexible hyaline cartilage.
• The posterior rib attachments are higher than the anterior joints, so the ribs have a downward slant, like the handle of a bucket.
• All of these articulations give the ribs two basic arcs of rotation called the pump handle and the bucket handle movements:
1. In the pump handle movement (A), muscle contraction rotates the rib heads around the costovertebral joints. This rotation
pulls up the distal ends of the ribs, especially ribs 2 through 7, lifting the sternum and displacing it anteriorly. This rotation
increases the anteroposterior (front to back) dimension of the thorax.
2. In the bucket handle movement (B) the same muscle contraction rotates the long axis of the ribs and reduces their
downward slant. This movement increases the lateral (transverse) dimension of the thorax.

Reference: Note, Text pg. 174-75 (Fig. 9-19, 9-20) 12

 Adult Thorax: Thoracic Wall Cross Section
• The external surface of the
thorax (skin of the chest wall) is
where the examiner places his or
her hands for palpation and
percussion and where the
stethoscope diaphragm is placed
for auscultation.
• The thorax is covered with
integumentary tissue (skin and
subcutaneous fat) over a layer of
skeletal muscle.
− Fascia (a type of connective
tissue) covers the muscle
and anchors it to any
adjacent tissues.
• The shape and orientation of the
ribs determine the shape of the
thorax.
− The normal adult thorax is
elliptical (its transverse
dimension is greater than its
anteroposterior dimension).
• The complex articulations
between the thoracic vertebrae,
the ribs and costal cartilages,
and the sternum produce a
series of skeletal arches and
planes that both stabilize the
thorax and limit thoracic
movement during breathing.
Reference: Note, Text pg. 173 (Fig. 9-17) & Text, Ch. 21 13
Cardiopulmonary Anatomy &
Physiology
RTT 100
Professor Michael Nazzaro
Supplement to Text, Chapter 8
The Respiratory System
You must study BOTH the chapter
and this supplement
Section 2a
The Adult Thorax
Respiratory Muscles

14
 Respiratory Muscles: Introduction
• Each breath, whether it is spontaneous* or produced by a ventilator, consists of two separate
phases: an Inspiration (inhalation) followed by an Expiration (exhalation).
• Spontaneous inspiration always requires the active expenditure of muscle energy.
• Expiration is a passive process during normal, quiet (resting) breathing.
– Passive means that there are no active muscle contractions when we exhale. The pressure to push the
air out comes from the potential energy that was stored in the elastic fibers of the alveoli and the elastic
chest wall structures during inhalation.
• Inspiration occurs when the volume of the thorax increases as the diaphragm muscle contracts
to a smaller size and the intercostal muscles cause the ribs and sternum to move superiorly,
anteriorly, and laterally.
– Boyle’s Law (Text pg. 120) states that when the volume of a container increases, the pressure inside the
container decreases. Boyle explains why air is drawn into the lungs during spontaneous inhalation.
• Most texts divide the respiratory muscles into two broad categories: Primary Muscles and
Accessory Muscles or Muscles of Inspiration and Muscles of Expiration.
–The diaphragm and the external intercostals are the primary respiratory muscles. They are used both
during quiet breathing (when we are not exercising) and during exercise.
–In healthy people, the accessary muscles are progressively recruited (come into use) when ventilatory
demand increases during strenuous exercise (such as running in a race).
• During maximal exercise the accessary muscles function during inspiration and during
expiration to expand and compress the thorax during breathing.
–In disease, particularly COPD, the accessary muscles are used when the diaphragm no longer functions
adequately because the hyperinflated lungs push it down into a mechanically disadvantageous position.
• For simplicity, writers discuss the muscles of breathing separately, but normally the muscles
function in unison (at the same time) in a coordinated manner.
*Spontaneous simply means that the control of breathing comes from the patient’s nervous system and the energy comes
from the patient’s respiratory muscles. In other words, the patient is not on a breathing machine (ventilator). Normal
individuals breathe spontaneously, but not all spontaneous breathing is normal. For example, COPD patients who are not
on a ventilator and asthmatics during an asthma attack are breathing spontaneously, but their breathing patterns are not
normal.

Reference: Text pg. 175-80 15

Respiratory Muscles: Primary & Accessory Muscles
Tables 8-4 and 8-5 organize the respiratory muscles into two groups: Muscles that Expand the Thorax During
Inspiration, and Muscles That Compress the Thorax During Expiration. The tables are correct but the simple
division of muscles into an Inspiratory and an Expiratory group is misleading for several reasons:
1. During normal, quiet (resting) breathing by healthy people, the Primary Muscles (the diaphragm and the
external intercostals) are used for every inspiration.
2. During normal, quiet breathing the energy for exhalation comes from elastic recoil, not from active muscle
contraction.
3. During energetic (during maximal exercise) breathing by healthy people, the accessory muscles function
both during inspiration to expand the thorax and during expiration to compress the thorax.
4. Patients with advanced COPD have little or no use of the diaphragm muscle, therefore, for those patients,
the Accessory Muscles of Inspiration become the Primary Muscles of breathing to expand the thorax. They
also use the accessory to help exhalation. This makes both inspiration and expiration active muscle events.

• The Accessary Muscles

come into use when
ventilatory demand
increases or when the
diaphragm is no longer
able to function
adequately.
• These muscles have a
primary purpose such as
moving the head, arms
and shoulders, and
supporting the abdomen
and back.
• The origins and
insertions shown in the
Tables refer to the
accessary muscle actions
when the shoulder girdle
is stabilized by bracing
the arms on a stationary
object (the so called
tripod position or
emphysematous habitus).
Accessary Muscles Anterior Accessary Muscles Posterior
Reference: Text pg. 176 (Table 9-4 & 9-5), 179 (Rule of Thumb) 16
 Respiratory Muscles: Primary Muscles
• The diaphragm is the major and most
important muscle of ventilation along
with the external intercostals.
• Normally the diaphragm alone
provides nearly all the energy needed to
breathe
− It accounts for about 75% of the change in
thoracic volume during quiet, resting
External breathing.
Intercostal
muscles
• Normal diaphragmatic excursion is
relax about 1.5 cm (the normal range ≈ 1-2
cm).
• Maximal contraction is about 10 cm.
– Each centimeter of diaphragmatic
movement increases thoracic volume by
about 350 ml and moves ≈ 440 ml of air.
•The accessory inspiratory muscles
provide a large reserve capacity for
breathing when we have to increase
ventilation during exercise.

• In some disease conditions (especially advanced COPD), the hyperinflated lungs push the diaphragm down
into a flatter position. This reduces the diaphragm’s mechanical efficiency.
• In these conditions the accessory muscles can provide adequate resting* ventilation with little or no
contribution from the diaphragm.

*Resting means that the patient is not exercising, and exercise includes just about every kind of
movement, including such things as combing the hair, shaving, and walking to the bathroom. A key
feature of COPD is severely reduced exercise tolerance.
Reference: Text pg. 176 (Table 9-4), 177 (MINI CLINI) 17
 Respiratory Muscles: The Diaphragm 1
The diaphragm is a dome shaped skeletal muscle. Its convex superior surface forms the floor of the thoracic
cavity and its concave inferior surface forms the roof of the abdominal cavity. The diaphragm develops from
the fetal mesoderm and is complete by about the 7th gestational week
• The muscle fibers of the diaphragm are
divided into two functionally separate
groups: the costal fibers and the crural
fibers. The fibers are arranged in a
radial configuration and converge
(come together) at a fibrous
aponeurosis called the central tendon.
– Muscle fibers of the thoracic diaphragm
are estimated to be about:
• 55% slow oxidative.
• 21% fast oxidative.
• 24% fast glycolytic.
– The anterior costal fibers originate from
the inner borders of the lower ribs and the
posterior aspect of the xiphoid process.
The anterior portion is called the sternal
diaphragm.
– The lateral costal fibers originate from the
medial surface of ribs 7 to 12 and are
attached to the abdominal wall muscles on
either side. The lateral portions are called • The central tendon divides the diaphragm into two leaflets
the costal diaphragm. called hemidiaphragms.
• The left and right hemidiaphragms each receive motor
– The posterior crural fibers originate from impulses from a separate branch of the phrenic nerve on the
the first three lumbar vertebrae (L1 to L3) corresponding side. The nerves originate from cervical spinal
and form two bands of muscle called the nerves C3, C4, C5.
left and right crura. The crura are not − Normally both hemidiaphragms move in synchrony, but
attached to the ribs. The posterior portions separate innervation allows one side to function even if
are called the lumbar diaphragm. nerve damage paralyzes the other side
Reference: Note, Text pg. 175-78, (Fig. 9-21) 18
 Respiratory Muscles: The Diaphragm 2
• The superior (cranial) surface of the diaphragm is covered with the same serous membrane,
the (parietal) pleural layer, that lines the inside of the thorax and the outer aspect of the
mediastinum. The inferior (caudal) surface is covered with the same serous membrane the
(peritoneum), that lines the abdominal cavity..
• The large right lobe of the liver is located below the dome of the right hemidiaphragm. When
the body is in the upright position at the end of a quiet expiration (the diaphragm relaxed) the
liver pushes the right hemidiaphragm about 1 cm higher than the left hemidiaphragm.
– The liver, the esophagus, and part of the colon are attached to the diaphragm by
ligaments.
• In the supine position, the abdominal contents push the diaphragm up and limit its downward
excursion reducing thoracic expansion and limiting inspired tidal volume (VT).
– This explains why patients with lung disease often find breathing easier in the upright
position.
The diaphragm has three As the animation at left shows:
major openings • When the diaphragm
(hiatuses): contracts and the ribs and
• The aortic hiatus. sternum expand, thoracic
• The esophageal hiatus. volume increases and
• The vena caval hiatus. pressure inside the chest
decreases.
An abnormal condition – As a result air flows in.
called hiatus hernia • When the diaphragm relaxes,
occurs when the upper the thoracic volume
part of the stomach decreases and pressure
protrudes into the thorax inside the chest rises.
through a weakened area – As a result, air is pushed
or a tear in the
diaphragm. out.

Reference: Note 19
 Respiratory Muscles: The Intercostals
The attachments and function of the intercostal muscles is much more complicated than the text indicates. There are 3
layers of intercostals: external, internal, and infracostal (or innermost).
• The external intercostals that connect ribs 1-11 are the outermost of the three layers of the intercostal muscles.
– They attach to the inferior margin of the rib above and are oriented obliquely downward and anteriorly to attach to
the superior margin of the rib below.
– The fibers extend from the tubercle posteriorly of the rib to the costochondral junctions anteriorly.
– The fibers of the lowermost 7 or 8 external intercostals blend with the external oblique muscle of the abdomen.
• When the first 4 or 5 external intercostals contract, they increase the thorax transverse diameter (bucket
handle effect) and flex the sternum to increase the anterior-posterior (AP) diameter (pump handle effect).
The internal intercostals have a more complicated role
since portions of the internals function as part of both
the inspiratory and expiratory accessory muscle
groups:
• As the illustration shows, the 11 pairs of internal
intercostals lie deeper than the externals and their
fibers are orientated at right angles to the fibers of the
externals. The illustration doesn’t show that the two
sets are separated by a layer of loose (areolar)
connective tissue.
– The internals arise from the superior margins of
the ribs and costal cartilages and pass obliquely
upward and anteriorly.
– They insert on the inferior margins of the rib
above.
• The internal intercostal muscles are often referred to as
if they were two separate muscle groups: The
parasternals or interchondrals (near the sternum) and
the interosseous between the ribs).
– Both the parasternals and interosseous are
between the ribs, but the parasternals also have
an upper insertion into the sternum.
• Contraction of different portions the internal
intercostal muscle fibers perform different functions:
– Contraction of the parasternal parts of the upper 4
or 5 internals tends to raise the ribs and assist the
externals during inspiration.
During quiet breathing, the internal intercostal’s main role appears to be to – Contraction of the interosseous parts of the lower
stabilize the chest wall and keep the lungs from bulging through the intercostal 7 or 8 internals depresses the ribs and assist
spaces. during expiration.

Reference: Note, Text pg. 175 20

 Respiratory Muscles: Primary Muscles Summary
The thoracic diaphragm and the external intercostal muscles are the primary muscles of inspiration. They are
active during resting breathing and during what the text calls stress induced increases in breathing. The text
means the stress produced by exercise (whether the exercise is recreational sport or induced by stimulation of
the flight or fight response.

(1 mmHg below ambient)

(In the PSIG scale 0 = 760 mmHg)

(1 mmHg above ambient)

Use of accessory muscles by ANY person AT REST (not actively exercising) is a

sign of respiratory distress
21
Respiratory Muscles: ‘Inspiratory’ Accessory Group
The arbitrary division of the accessory muscles of breathing into an Inspiratory Group
and an Expiratory Group is an incorrect oversimplification. During energetic
breathing (as in exercise) and forced expiration (as in COPD), some of the accessory
muscles are active during both the inspiratory and expiratory phase.

Muscle Origin Insertion Normal Action Action in Breathing

Scalene Anterior Transverse First rib Rotate the head (as if Elevate 1st ribs
Process of C3-C6 to say “No”)
Scalene Medial Transverse First rib “ Elevate 1st ribs
Process of C2-C7
Scalene Posterior Transverse Second rib “ Elevate 2nd ribs
Process of C4-C6
Sternal Head & Mastoid Flex & extend, tilt and When the head is
Sternocleidomastoid Manubrium. Process (on rotate the Head. Other held fixed, elevates
(aka Strap muscles) Clavicles. either side) & complex head & neck the sternum & 1st rib
occipital bone movements
Trapezius Occipital bone & Clavicles & Move the shoulders Fixes the head
spines of C7-C12 scapulae (shrug, etc.)
2nd or 3rd – 4th or Abducts & rotates Elevated 3rd – 5th
Pectoralis Minor 5th Ribs Scapulae scapulae downward ribs when scapulae
are fixed
Clavicle, sternum, Rotates arm at
Pectoralis Major costal cartilages of Humerus shoulder & other arm Lifts sternum
2nd – 6th ribs movements

Reference: Text pg. 176 (Table 9-5)

22
Respiratory Muscles: ‘Expiratory’ Accessory group
Muscle Origin Insertion Normal Action Action in Breathing

External Iliac crest & Compress the abdomen Compress ribs & pull
Oblique Ribs 5 to 12 linea alba & flex the vertebral abdominal wall inward
column
Internal Iliac crest, Cartilage of ribs
Oblique inguinal ligament 7 to10 & the “: “
linea alba
Iliac crest, Xiphoid Support & protect the
Transverse inguinal ligament, process, linea abdominal viscera and “
abdominus thoracic & lumbar alba, pubis allow performance of the
vertebrae Valsalva maneuver.
Rectus Pubic crest & Cartilages of
abdominus pubic symphysis ribs 5 to 7 & “ “
xiphoid process
Compress ribs when arms
Serratus Superior aspect Scapula Abducts & rotates are fixed and elevates the
anterior of ribs 8-9 scapula ribs when the scapula is
fixed
Serratus Spinous Upper boarders Elevates ribs during
posterior processes of C7 of ribs 2 to 5 energetic breathing
superior to T2
Serratus Spinous Inferior Pulls lower ribs inferiorly Compresses ribs during
posterior processes of T11 boarders of ribs and posteriorly to aid in forced exhalation
inferior to L2 9 to12 movement
Spines of T7 to
L5, & the 4 Extends, adducts, & Costal attachment assists
Latissimus inferior ribs Humerus rotates arm medially at in energetic inspiration
dorsi via the the shoulder joint and expiration
thoracolumbar
fascia

Reference: Note, Text pg. 176 (Table 8-5) 23

 Respiratory Muscles: Accessory Muscle Notes
On pg. 178 the text states “when alveolar pressure drops to -10 cmH2O the scalenes are active in all subjects.”
The idea the writer was trying to express is that when ventilatory demand and/or airway resistance increases to
the point where the subject has to increase WOB to a level that reduces intraalveolar pressure to -10cmH2O, the
subject has to recruit the scalenes and sternocleidomastoid muscles.
• While there is general agreement that the external intercostals do expand the rib cage during inspiration.
• There is still controversy over whether the internal intercostals act to expand the ribs during breathing at rest.

Active use of accessary muscles at rest indicates an abnormal

increase in the work of breathing. Accessary muscle activity
produces clinical signs that are usually easy to observe.
• Tripod position allows the patient to fix the head and the
pectoral (shoulder) girdle allowing the pectoralis muscles to
generate some anterior thoracic lift.
• Trapezius muscle use usually produces visible clavicular lift
where the clavicles rise > 5 cm with each inspiration.
• Strap muscle use produces a visible rise in the anterior upper
chest.
• Retractions when airway resistance is high the patient must
produce a large trans-chest wall pressure gradient (PTCW ).
This causes atmospheric pressure to press the skin of the
chest tightly against the ribs during spontaneous inspiration.
• Abdominal paradox is often seen in patients with advanced
COPD who have an atrophied, weakened diaphragm.
– When the accessory muscles lower intrathoracic pressure the
flaccid diaphragm is drawn upward into the thoracic cavity and the
anterior abdominal wall is drawn inward.
• Respiratory alternans occurs in patients who retain some
use of the diaphragm. They use accessory muscles for several
This subject is breathing minutes then switch to the diaphragm for several minutes.
spontaneously, but his breathing
is not normal. Reference: Note, Text pg. 177 (Mini Clini), 179 (Rule of Thumb). 24
Cardiopulmonary Anatomy &
Physiology
RTT 100
Professor Michael Nazzaro
Supplement to Text, Chapter 9
The Respiratory System
You must study BOTH the chapter
and this supplement
Section 2b
The Adult Thorax
The Pleura

25
 The Pleura: Function & Naming
• The pleura is the folded over serous membrane that
surrounds the “pleural space,” covers the lung, and
lines the thoracic cavity.
• The parietal pleural layer lines the inner surface of
the thoracic cavity, including the mediastinum, the
diaphragm, and the ribs:
– Different sections of this layer are named for the
structures they cover (see Note).
• The Visceral pleural layer covers all the surfaces of
the lungs, including the inter-lobar fissures
• Both layers are smooth and shiny, but they have
major anatomic differences in blood supply,
innervation, lymphatic drainage, and physiologic A C
function, for example: B
– There are no pain sensing nerve fibers in the visceral
pleura.
– The visceral layer also has a dual blood supply; from both
the bronchial and pulmonary vessels
• The visceral and Parietal layers join at the hila where
airways, blood vessels, and nerves enter the lungs.
– The pleural layers do not wrap around the hila.
• The visceral and parietal pleural layers are flush
against each other, normally separated only by the • The parietal pleural layer lines the thoracic wall
thin layer of pleural fluid and the superior surface of the diaphragm (A and
– The parietal layer normally remains attached to the chest B).
wall (the ribs tend to spring outward). • It continues around the heart forming the lateral
– The visceral layer normally remains attached to the lung walls of the mediastinum (C).
surface (the elastic lungs tend to contract inward). • The visceral pleural layer extends over the
• These attachments tend to pull the pleural layers surface of the lungs.
apart slightly producing a subambient pressure in the • The rim of the lung bases are seen above the
pleural space according to Boyle’s Law. hemidiaphragms
− The surface tension of the fluid in the pleural cavity acts to • The costophrenic angles are formed by points
hold the pleural layers together. where the hemidiaphragms meet the chest wall
− The layers can slide up and down and from side to side
but it is hard to separate them. Reference: Note, Text pg. 180, 438, 560 26
Cardiopulmonary Anatomy &
Physiology
RTT 100
Professor Michael Nazzaro
Supplement to Text, Chapter 9
The Respiratory System
You must study BOTH the chapter
and this supplement
Section 2c
The Adult Thorax
The Lungs

27
 The Lungs & Mediastinum: The lungs Overview
• The lungs are light, soft, spongy,
elastic, organs that contain air.
Normally, they float in water when
removed from the thorax during
autopsy. After removal from the
thorax, the lungs quickly collapse.
• The left lung is slightly narrower
because its cardiac notch has to
make room for the heart. The right
lung is slightly shorter because it
has to make room for the liver, but it
is wider because the mediastinal
structures bulge into the left
hemithorax.
• Each lung is enclosed in its own
pleural sack. Each lung is attached
to the heart and trachea by its root,
and each lung is attached to the
pericardium by its pulmonary
ligament. Otherwise, the lungs are
free in the thoracic cavity.
– The lung root consists of the
bronchi that extend from the
trachea, and the pulmonary
vessels that extend from the
heart. These structures are
Domes of the hemidiaphragms covered with the part of the
pleura where the parietal pleura
reflects to the visceral layer. The
Major arteries and veins showing the complex vascularization of the lungs bronchi and pulmonary vessels
enter (and leave) each lung
• Around the 56th day of fetal life, the bronchial buds develop into recognizable lung through the part of the medial
lobes. pleural surface called the hilus.
• These lung lobes are separated by open spaces called fissures.
• As the lungs grow, the fissures become very narrow, and the pleura reflects into – The pulmonary ligament is a fold
them. of the pleura that connects the
• The fissures are thought to facilitate movement of the lobes relative to each other medial aspects of the lung root
and allow greater distension of the lower lobes during breathing. to the pericardium.
• The right lung is divided into three lobes: Upper, Middle, and Lower separated by a Reference: Note, Text pg.
horizontal and an oblique fissure. 173, 182 (Fig. 9-28-29)
• The left lung only has two lobes, separated by an oblique fissure.
28
 The Lungs & Mediastinum: The Lungs
•The division of the
lung into lobes,
segments, and
lobules tends to
make each
subdivision into a
functionally
independent unit.
– This helps to
reduce the
spread of
infection in the
lung.
• Familiarity with
bronchopulmonary
segmentation is
essential to
successful
performance of the
patient assessment
skills including:
– Percussion,
– Auscultation, and
Chest.
– X-Ray
interpretation.
Reference: Text pg. 181-83 (Fig. 9-28), 195 (Fig. 9-42), 198 (Fig. 9-45). 29
Cardiopulmonary Anatomy &
Physiology
RTT 100
Professor Michael Nazzaro
Supplement to Text, Chapter 9
The Respiratory System
You must study BOTH the chapter
and this supplement
Section 2d
The Adult Thorax
Pulmonary vasculature , lymphatics, &
Innervation
30
 Cardiovascular System: Pulmonary & Systemic
THE BODY HAS TWO VASCULAR SYSTEMS:
1. The systemic circulatory system (aka the systemic arterial tree), consists of all the vessels that branch from
the aorta which emerges from the left ventricle, all the way around to the right atrium.
• The systemic arterial tree is a high pressure, high resistance, long distance system that carries
oxygenated (arterial) blood to the systemic capillary beds ant the tissue cells of the body.
– The coronary and bronchial circulations are subsets of the systemic circulation
2. The pulmonary circulatory system consists of all the vessels from the pulmonary artery which emerges
from the right ventricle, all the way back to the left atrium.
• The pulmonary circulatory system is a low pressure, low resistance, short distance system that carries
deoxygenated (venous) blood to the pulmonary capillary beds where gas exchange occurs.

Reference: Note, Text pg. 183 (Fig. 9-30), 215-16 & Figs. 10-6 & 10-7. 31
 Vascular System: Functions
There are 5 main blood vessel types :
Arteries, arterioles, capillaries, venules, and
veins.
• The purpose of the circulatory system is to perfuse
the vast network of capillaries in the body to perform at Arterial ends
least three functions:
1. Regulate body temperature,
2. Supply oxygen and nutrients to the cells, and Venous ends
3. Remove waste materials, including CO2, from
the cells.
• In most tissues arterioles terminate in a branching
network of 10 to 100 capillaries called capillary beds.
• Capillary density (the number of capillaries in a
specific tissue) depends on the type of tissue, for
example:
- The thyroid gland has dense capillary networks
while the cornea of the eye has sparse networks
• Capillaries are about 1 mm long and 5 to 10 microns
in diameter. Capillaries are narrower than red blood
cells (RBCs), but RBCs are flexible so they can
contort to pass through the capillaries.
– The capillary wall consists of a single layer of
endothelial cells with fairly loose junctions
between the cells.
• The end of the arteriole, near the point where the
capillaries branch off, is called the metarteriole.
– The smooth muscle of the arteriole’s tunica media
forms a muscular ring at the metarteriole. The
ring is called a precapillary sphincter that
controls blood flow into the capillary bed.
• In some capillary beds an arteriovenous (AV) shunt
vessel or thoroughfare channel may be present that to
carry blood directly from the arteriole to the venule.
- Thoroughfare channels are a bypass shunt
through the tissue.
- Blood flow through AV shunts is called non- Capillary perfusing tissue cells showing capillary filtration
nutrient flow. and reabsorption, and lymphatic drainage.
Reference: Note, Text pg. 184 (Fig. 9-31) 32
Cardiovascular System: Pulmonary & Systemic Pressures
The pulmonary vessels are thin walled vessels
that have a larger internal diameter (lumen) and
less vascular smooth muscle than the systemic
blood vessels.
• The pulmonary circulation rapidly divides into
about 280 billion capillaries (the alveolar
vessels).
– They form a virtual sheet of blood around
the alveoli.
• Pulmonary capillaries are more distensible and
compressible than the systemic capillaries and
they present less resistance to blood flow.
– Alveolar capillaries are subject to both
alveolar and pleural transmural pressures.
– They also have characteristics that let them
perform activities called Recruitment and
Distension (Slide 48).
– These characteristics account for the low
resistance of the pulmonary circuit,
• The pulmonary vessels need less
intravascular pressure from the right ventricle
than the systemic vessels require from the left Systemic and pulmonary circuit pressures in arteries, arterioles,
ventricle. capillary beds, venules, and veins.

Dense
capillary
networks
surround
each
alveolus
and form a
virtual sheet
or lake of
blood
around each
air sac.

Reference: Note, Text pg. 183, 214, 280, 1177 & Fig. 51-10, 1178 (Table 51-3) 33
 Capillary Fluid Exchange: Filtration & Reabsorption Body fluids are located in two major fluid
Hydrostatic pressure Plasma osmotic Hydrostatic pressure compartments:
at the arterial end of pressure (inside the at the venous end of the intravascular compartment and the
pulmonary capillaries capillary) ≈ +25 pulmonary capillaries
≈ +8 mmHg mmHg ≈ +5 mmHg
extravascular compartment.
• All the blood in the heart and blood vessels is in
Lymph fluid
the intravascular compartment.
that is not • All the other body fluids are located in the
reabsorbed at extravascular compartment.
Interstitial the venous end • The extravascular compartment has many
osmotic of the capillary subcompartments including the intracellular,
pressure ≈ +19 becomes part interstitial, and lymphatic compartments.
mmHg. of the • Movement of fluid (mostly water), and
Interstitial intracellular electrolytes, and low molecular weight solutes,
hydrostatic fluid.
pressure ≈ -2 Lymphatic between the compartments is controlled by
mmHg. capillaries aid physical forces including:
in preventing • Hydrostatic as well as osmotic and oncotic
tissue edema. pressures, and capillary wall permeability.

Note to the figure above:

The capillary and interstitial hydrostatic and osmotic pressures shown are
averages for pulmonary capillaries in normal, healthy individuals.

•Of the fluid that filters out of the arterial end of the capillaries, about 90% is
reabsorbed at the venous end.
•The 10% that isn’t reabsorbed (about 3 liters/day) becomes part of the
interstitial fluid that surrounds the tissue cells.
•Lymphatic capillaries pick up the excess interstitial fluid and proteins and
return them to the venous blood.
– The fluid that filters out of the capillaries is called lymph.
Animation showing how
hydrostatic pressure in
the interstitial space
pushes fluid into the
terminal lymphatic
capillaries.
Lymphatic drainage of
tissue interstitial spaces Closed ended lymphatic capillaries are
is essential to prevent interspersed with blood capillaries in the
edema. interstitial space

Reference: Note, Text pg. 184 (Fig. 9-32), 271-72 34

Cardiovascular System: Pulmonary Vascular System
Transmural pressure exerted on the capillary by alveolar expansion • Pulmonary capillaries are thin walled,
collapsible (compliant) structures. Each
capillary covered alveolus shares space in
the chest with the other 300 million
alveoli, so the capillaries are subject to
the alveolar pressure in the lungs.
• Their high compliance allows them to
change diameter according to changes in
Arrows transmural pressure (pressure across the
indicate low capillary wall).
pressure
around extra- • At rest the pulmonary capillary beds
alveolar contain about 60-80 mL of blood. This
vessels volume can expand to 200 mL during high
cardiac output conditions.
Intravascular (hydrostatic) pressure
• The total pulmonary blood volume is
about 600 ml.
•Recruitment and Distension are names
for two ways the pulmonary vascular
system maintains its low resistance
despite changing blood volume and
maximizes perfusion to ventilation (V/Q)
matching.
– Recruitment means that compliant
vessels in a partially collapsed state
are reopened by intravascular
pressure.
– Distension means that already open
capillaries can be expanded even
more by intravascular pressure.
• Extra-alveolar vessels include arterioles
(resistance vessels) and venules
(capacitance vessels).

Distension & Recruitment of pulmonary capillaries Reference: Note 35

 Sites of Gas Exchange: Pulmonary Interstitium
Please note that the cells in the figure are NOT drawn to scale • The space between the alveolar
and capillary walls is the
pulmonary interstitium.
•The interstitium is a matrix
made up of collagen and elastic
fibers.
•These fibers support the AC
MATRIX structures, allow lung
expansion, and limit alveolar
over distension during
inspiration.
• The interstitium has both
Tight Space TIGHT SPACES (thinner
interstitium) and LOOSE
SPACES (thicker interstitium).
– Most gas exchange occurs
across the tight space.
– The loose space contains
lymph vessels & nerve
Loose Space fibers.
• The JUNCTIONS between the
alveolar epithelial cells (Type I
pneumocytes) are TIGHT
junctions because they normally
prevent passage of liquids.
• As we have seen, some
capillaries have loose
JUNCTIONS between the
endothelial cells. These loose
junctions make capillaries more
permeable to liquids.
The basement membranes of the alveoli and the •Pulmonary capillaries have
alveolar capillaries (their walls) form an extremely thin relatively TIGHT junctions
although the capillary
“barrier” to gas exchange that is only about 0.5 μ endothelial cell junctions are
thick. looser than the alveolar
epithelial cell junctions.
Reference: Note,
Text pg. 197, 203-05. Don’t confuse Tissue SPACES with Cell JUNCTIONS 36
 Lymphatic System: Structure
The lymphatic system consists of lymph fluid (called
lymph) flowing through lymphatic vessels (called
lymphatics), a number of structures that contain
lymphatic tissue, and the bone marrow where
lymphocytes are made.
• Lymph:
– A clear liquid with about the same composition as
interstitial fluid.
• Lymphatic vessels:
– Closed ended lymphatic capillaries are located
among the blood capillaries in the spaces between
the cells.
– Lymphatic capillaries drain into lymphatic vessels
(lymphatic veins) which resemble systemic veins
but have no basement membranes, thinner walls
and more valves (about one per millimeter).
– Lymphatic vessels pass through lymph nodes and
empty into the lumbar, intestinal,
bronchomediastinal, subclavian, and jugular
lymphatic trunks.
– The lymphatic trunks empty into the Thoracic (left)
Lymphatic Duct and the Right Lymphatic Duct.
– The ducts drain into the jugular and subclavian
veins.
• Lymph nodes:
– More than 100 tiny oval lymph nodes are scattered
along the lymph vessels and clustered in the neck,
the groin, and the axilla (arm pits).
•Reticular fibers in the lymph nodes filter foreign
substances from the lymph. Macrophages
destroy some substances by phagocytosis,
other lymphocytes destroy pathogens by various
other immune processes.
– The tonsils, spleen, and thymus gland are masses
of lymphoid tissue that behave somewhat like
organs.
Reference: Note, Text pg. 185-86 37
 Vascular System: Edema
• Edema (from the Greek word for swelling) results from an
increase in the amount of fluid in the interstitial space.
– The interstitial space is a subdivision of the
extravascular compartment.
– Fluid in the interstitial space is called interstitial fluid.
• Edema occurs when the rate of filtration of fluid out of the
capillaries exceeds the rate of capillary reabsorption plus the
fluid absorbed by the lymphatic capillaries (lymphatic flow).
– In other words; when the normal mechanisms that
ensure proper tissue fluid balance are disrupted.
• Edema may be local (found in one area of the skin) as in a
minor injury or insect bite.
• It can involve a whole limb as in lower legs in Figure B.
• It can involve a specific organ such as the lung in pulmonary
edema (Figure A).
• It can be generalized and effect the entire body (Figure B).
• Pulmonary edema is usually classified either as either
cardiogenic (hydrostatic) or non hydrostatic.
Hydrostatic pulmonary edema is due
to Non-hydrostatic pulmonary
Increased pressure in the pulmonary edema is due to increased
capillaries, most often caused by: capillary permeability, most
• Mitral valve stenosis (narrowing) of often caused by:
the valve between the left atrium • Damage to the capillary
and ventricle causing increased left membrane making it
atrial pressure. leaky.
• Left ventricular failure • Decreased plasma
(insufficiency) also increased left oncotic pressure from low
atrial pressure. plasma proteins resulting
• Systemic fluid overload may be from burns, liver failure,
caused by renal (kidney) failure, malnutrition, etc.
excess intravenous fluid • Lymphatic blockage from
administration, etc. tumor or infection.
Reference: Note, Text, pg. 280, 442 38
 Pulmonary Vascular Function: Normal
Three anatomic layers make
up the “barrier” that separates
the pulmonary capillary blood
from the gases (air) in the
alveolar sacs:
1. The endothelial cells of
the capillary wall, normally
with cell junctions that are
tight, but not as tight as
the alveolar cell junctions.
2. The highly compliant
interstitial space between
the capillary and the
alveolus.
• Lymphatic capillaries
(“channels”)are located
in the pulmonary
The figure shows a normal alveolus, alveolar capillary, and lymphatic interstitium.
capillary. 3. The epithelial cells of the
•The black and green arrows show fluid movement across the capillary wall. alveolar wall, normally
have tight cell junctions
•The thickness of the arrows represents the relative amount of fluid moving (Slides 36 & 103).
and the differences in pressure between the vessel and the tissue space. These anatomical features
•The lymphatic channel (capillary) is located in the interstitial space. tend to keep the amount of
fluid in the pulmonary
•Pink cells are alveolar epithelial cells, green are capillary endothelial cells. interstitium low.
•The lymphatic channel (capillary) drains excess fluid from the interstitium.
Fluid flux (back and forth movement) in the microcirculation (the capillaries) is described by Starling’s
equation (Starling forces).
• In simple terms, these forces are normally a balance between:
1. Hydrostatic pressure that tends to push fluid out of the capillary.
• Capillary pressure is normally higher at the arterial end and lower at the venous end.
2.Oncotic pressure that tends to draw fluid back into the capillary from the interstitial space.
3.Capillary wall permeability that generally limits movement of large molecular solutes.
• Excess fluid and large solutes (mostly proteins) are returned to the venous circulation by lymphatic
capillaries (lymphatics) located in the interstitial space.
Reference: Note Text pg. 280 & Fig. 13-6, 589-94 & Figs. 29-3 & 29-4 39
Pulmonary Edema: Hydrostatic Pulmonary Edema
Blood in this pulmonary capillary is flowing from left to right. More fluid leaves both the pulmonary arterial (blue)
end and the pulmonary venous (red) end of the capillary than is reabsorbed.

• The black arrows

represent the amount of
fluid leaving the
capillary.
• The green arrows
indicate the amount of
fluid being reabsorbed
into the capillary.
• The little circles
represent the actual
fluid.
• The interstitial space is
actually between the
capillary and the
alveolus (see Slides 48
& 103)
• Common causes of
cardiogenic pulmonary
edema include:
− Congestive heart
failure.
− Mitral valve stenosis.
− Left ventricular
failure (insufficiency).
− Lymphatic blockage.
− Local pulmonary
Pulmonary edema occurs when the volume of liquid moving into the capillary blockage by
pulmonary interstitium from the capillaries is greater than the amount of a thrombus.
fluid removed by reabsorption and lymphatic drainage.

Reference: Note, Text pg. 442, 590-94 40

 Pulmonary Edema: Non-Cardiogenic Edema 1
The pulmonary capillary is normal and undamaged. However, the alveolar epithelial cells are damaged and
cannot prevent fluid present in the interstitium from entering the alveolar air space

When alveolar epithelial cells

Alveolar Air Space (above the capillary) are damaged:
• The normally tight
junctions between alveolar
pneumocytes no longer
prevent fluid from entering
the alveoli.
• An excessive amount of
fluid leaves the interstitial
space and may flood the
alveolar air spaces.
• The lymphatic vessels may
become dilated for several
reasons:
– They may be overloaded
with fluid, or
– The lymph nodes may
The capillary endothelial cells (green) are intact, but the alveolar commonly be blocked by
epithelial cells (pink) have been damaged the antigen/antibody
complexes and cellular
debris from infection or
The lymphatic capillary may be dilated due to fluid overload by cancer (tumors).
or other causes such as infection or tumor • Lymphatic blockage will
reduce the amount of fluid
that can be collected by the
Common causes of alveolar epithelial cell damage that can produce non-cardiogenic lymphatic channel and
pulmonary edema include: cause the lymphatic
• Toxic damage to alveolar pneumocytes from high concentrations of oxygen. capillaries in the tissue
• Inhalation high concentrations of toxic gases such as nitrogen and sulfur oxides, and space to dilate.
ozone. • Again, the result will be an
• Near drowning where water has been aspirated. excessive accumulation of
• Destruction of alveolar cells by an overactive immune response to viral pathogens that fluid in the interstitium
causes hypercytokinemia (see Microbiology Background Slides 29 & 30). producing edema.
Reference: Text, pg. 442, 590-94 41
 Pulmonary Edema: Non-Cardiogenic Edema 2
Damage to the pulmonary capillary endothelial cells effectively increases the capillary permeability. Large amounts of
fluid leak through the excessively permeable (damaged) capillary wall.

Alveolar Air Space When the capillary

endothelial cells are
damaged
• Capillary wall
permeability
increases.
• The capillary becomes
“leaky.”
• More than the normal
amount of fluid leaves
the capillary and
enters the interstitium.
• Fluid can even force
The alveolar epithelial membrane (pink) is intact while the its way into the
capillary endothelial membrane (green) is damaged. alveolar air spaces.
• The lymphatic vessels
The lymphatic capillary is dilated, possibly from any of
may become dilated
the reasons listed before. for the same reasons
listed.
• Pulmonary edema from whatever cause will impose a pulmonary restriction (reduced alveolar expansion).
• Because it is difficult to breathe deeply, the patient will usually exhibit a breathing pattern displaying a rapid rate with shallow
i.e. low tidal volume (VT) breaths.
− This tachypnea may be due in part by stimulation of the J receptors near the pulmonary capillaries.
− The rapid rate will partially compensate for the inability to inhale a normal V T.
• Common causes of this type of pulmonary edema include:
• Acute Respiratory Distress Syndrome (ARDS).
• Sepsis, a systemic inflammatory response to infection.
• Pulmonary embolism.

Reference: Text, pg. 590-94 42

Cardiopulmonary Anatomy &
Physiology
RTT 100
Professor Michael Nazzaro
Supplement to Text, Chapter 9
The Respiratory System
You must study BOTH the chapter
and this supplement

Section 2e
Non-Respiratory Functions of the
Pulmonary System
Reference: Text pg. 185

43
 Adult Lungs: Non-respiratory Lung Functions
The lungs and the pulmonary circulatory system are primarily responsible for gas exchange, but
they are metabolically active and produce and manage substances that effect the entire body.
Some of these metabolic functions include:
1.Acting as a crucial step in the Renin-Angiotensin-Aldosterone System of enzymes; a system
that is extremely important in regulating blood volume, arterial blood pressure, heart muscle
function, and vascular function (by controlling the tone of vascular smooth muscle).
– The system is a complex mix of chemicals mainly produced by the kidneys (renin) and the
liver (angiotensinogen). Renin is the enzyme that converts angiotensinogen to angiotensin I.
– Cells in the pulmonary capillary endothelium are the main site for production of Angiotensin
Converting Enzyme (ACE). ACE is the enzyme that converts angiotensin I to the active form
Angiotensin II. Angiotensin II actions include:
• Constricts blood vessels (thereby controlling blood pressure).
• Stimulates the adrenal cortex to release aldosterone (which stimulates the kidneys to
retain sodium and fluid thereby increasing blood volume and pressure).
• Stimulates the pituitary to release vasopressin (which further stimulates the kidneys to
retain fluid).
• Stimulates thirst centers in the brain.
– All of these are normal responses to dehydration and hypovolemia (low blood volume).
– In certain disease states ACE inhibitors are given therapeutically to reduce blood pressure.
2.The majority of pulmonary thromboemboli resolve spontaneously, so there must be a fibrinolytic
system present in the pulmonary vasculature to dissolve (lyse) those clots
– Tissue plasminogen activator (t-PA), an enzyme that lyses clots, has been shown to be
present in the human pulmonary artery.
3.When damaged, lung cells release powerful signaling chemicals called chemokines that attract
immune system cells to the site of injury.

Reference: Text pg. 185 44

 Cardiopulmonary Anatomy &
Physiology
RTT 100
Professor Michael Nazzaro
Supplement to Text, Chapter 9
The Respiratory System
You must study BOTH the chapter
and this supplement

Section 2f
Neurologic Control
This topic is covered in greater depth in Chapter 15
Reference: Text pg. 186-88, 310-15

45
 Neural Control: Overview
• The respiratory system’s primary function is gas exchange to keep the arterial PO2 and PCO2 within their
normal ranges in order to maintain ventilatory homeostasis.
– The respiratory system can precisely control ventilation and maintain the PaO2 and PaCO2 within a narrow
range while adapting to meet the sudden changes in ventilatory demand produced by human activities that
range from quiet, resting breathing to vigorous exercise, not to mention speaking, singing, shouting,
coughing, blowing trumpets, vomiting, voiding, and childbirth; all of which require altered breathing patterns.
• Breathing is a rhythmic process that is mostly under autonomic control. While no specific central respiratory
“pacemaker” has ever been identified, physiologists conceptualize the existence of what might be called a
neurological Central Controller or Central Pattern Generator (CPG) to control breathing rhythmicity
– Such a CPG is not a single structure or area, but a complex of neurological structures that integrate inputs
from the many sensors located in the lungs, the airways, and throughout the body.
– The CPG then sends signals to the effectors, the respiratory and airway muscles, to establish the
appropriate breathing pattern (the rate and depth of breathing) and to change the tone of muscles in the
airways.
Central Controller or CPG
(Pons, medulla, Cortex)

Sensors Effectors
(Chemoreceptors, lung (Respiratory and airway
and other receptors) muscles)
Alveolar Ventilation

The normal negative feedback process of precise, rhythmic respiratory control:

The dashed arrow indicates that muscle activity increases or decreases ventilation and corrects the PO 2 (and/or) PCO2
changes (imbalances) that stimulated the sensors.

• Spontaneous inspiration begins when nerve impulses cause the diaphragm and external intercostal muscles to
contract. This expands the thorax and reduces intrathoracic, intrapleural, and intraalveolar pressures to a level slightly
below atmospheric pressure. As a result of this inspiratory pressure gradient, air flows into the lungs.
• Expiration occurs when the nerve impulses to the respiratory muscles stop. Without nerve stimulation the muscles
relax and the thorax contracts to its pre-inspiratory size. Thoracic contraction and elastic recoil cause the
intrathoracic, intrapleural, and intraalveolar pressures to increase to a level slightly above atmospheric. As a result of
this expiratory pressure gradient, air flows out of the lungs.
• Whether normal spontaneous breathing is quiet or energetic, under voluntary or autonomic control, the process is
rhythmic and coordinated with a high level of efficiency

Reference: Text pg. 186-88, 309 46

 Neural Control: Sensors Overview
Sensors that effect breathing include:
• Central chemoreceptors in the medulla.
• Peripheral (arterial) chemoreceptors in wall of the aorta and carotid arteries.
• Irritant receptors located between the alveolar epithelial cells and in the nose and upper airway.
– The central and peripheral chemoreceptors are the most important sensors.
• Stretch receptors in the lungs.
• Juxtacapillary (J) receptors located near the pulmonary capillaries that respond to pulmonary capillary
engorgement.
• Capillary (C) receptors located near the bronchial capillaries respond to the chemical content of bronchial
capillary blood.
• Muscle fiber elongation (gamma) receptors located in the respiratory and other skeletal muscles.
• Pain and temperature sensors located throughout the body

Peripheral Chemoreceptors located in the carotid

Central Chemoreceptors located in the medullary pons arteries and aorta

Reference: Note, Text pg. 187, 312-14 47

 Neural Control: Central Chemoreceptors
• The central chemoreceptors Central chemoreceptors are located near the ventrolateral surface of the
medulla slightly below the surface) close to the point in the medulla
respond (send signals to the where the 9th and 10th nerves exit. Hydrogen ions in the CSF control the
brain) when the H+ concentration level of stimulation of the central receptors.
in the CSF and brain ECF
changes.
– Changes in the PCO2 of the cerebral
capillary blood directly affect the H+
concentration (pH) of the CSF and
the brain ECF. The “blood-brain barrier”
is not a membrane. The
• Increased H+ concentration in the “barrier” refers to the
ECF stimulates ventilation. fact that the endothelial
cell junctions of the
– The brain signals the respiratory cerebral capillaries are
muscles to increase work. tighter than the
junctions in other
– The respiratory rate and tidal volume capillaries.
(depth of breathing) increase.
• Decreased H+ concentration in the
ECF inhibits (reduces) ventilation.
– The brain signals the respiratory
muscles to do less work.
– The respiratory rate and tidal volume
decrease.
• Central chemoreceptor stimulation
is the primary neurological drive to
breathe.
– The PaCO2 of the blood reaching
the brain is the primary source of
the signals that control the rate Central chemoreceptors are
and depth of breathing in normal Cerebral Cerebrospinal fluid bathed in the brain extracellular
people. capillary (CSF) fluid (ECF)

Reference: Text pg. 312 (Fig. 15-4). 48

 Neural Control: Peripheral Receptors
The Peripheral Chemoreceptors are two groups of
small, highly vascularized tissue cells that can
detect concentrations (pressures) of various
substances. They are called the carotid and aortic
bodies:
• Carotid bodies, located at the bifurcation of the
common carotid artery and innervated by the
glossopharyngeal (9th cranial nerve).
– The carotid bodies are only a few millimeters in
size but they have the highest blood flow per
tissue weight of any structure in the body.
- The carotid bodies are comprised of several cell
types, with glomus cells making up the largest
number.
- Carotid body cells are primarily sensitive to
increased H+ concentration (decreased pH) in
arterial blood.
- Low pH most often results from increased
PaCO2 but these cells also respond to increased
H+ concentration from metabolic causes of
acidemia
• Aortic bodies, located above and below the arch of
the aorta and innervated by the vagus (10th cranial
nerve).
– The aortic bodies appear to be less important
than the carotid bodies.
• The peripheral chemoreceptors have a high
metabolic rate.
– This rate is supported and a very high blood
flow of about 2000 ml/100 g of tissue. Location and innervation of the peripheral
receptors.
– As a result, it difficult to detect a PO2 difference
between the blood entering and leaving the Location and innervation of the peripheral receptors.
carotid and aortic bodies Reference: Note, Text pg. 312 49
Neural Control: Central Control & Rhythmic Breathing
Nerve signals for rhythmic breathing originate in the brainstem.
Although no central controlling “pacemaker” for rhythmicity has
been identified, three main groups of neurons located in the
medulla appear to be the source of control for rhythmic breathing:
1. Cells in the ventrolateral region of the medulla called the pre-
Botzinger complex appear to be essential for controlling
breathing rhythmicity.
2. Cells in the dorsal region of the medulla, the nucleus of the
tractus solitarius (NTS) are called the dorsal respiratory group
(DRG) and mainly contain inspiratory (I) neurons.
•DRG neurons receive signals from many sensors including
the central and peripheral chemoreceptors.
•DRG I neurons send impulses to the spinal motor nerves that
control the diaphragm and the intercostals.
3. Cells in the ventral region called the ventral respiratory group
(VRG) are divided into a Rostral (toward the head) and Caudal
(toward the tail) group.
• The most rostral portion of the VRG is the Botzinger
complex.
• It contains both expiratory (E) and I neurons, but the VRG
appears to be chiefly associated with expiration.
• The apneustic center is located in the lower pons (medullary
pons).
– It is not know if it functions in normal breathing, but if an
animal’s pons is transected just above the site (Roman
numeral II) apneustic breathing (prolonged inspiratory
gasping with occasional expiratory efforts) will result. In
some patients with severe neurologic damage apneustic
breathing is observed.
• The pneumotaxic center is located in the upper medullary pons.
– This center has been shown to stop inspiration when
stimulated in lab animals. Stopping inspiration is probably a
way to increase the respiratory rate and lower the inspiratory
volume.
The brainstem connects the cerebral hemispheres with
– Some physiologists think that the normal function of the the spinal column. It consist of the midbrain, the pons,
pneumotaxic center is to “fine tune” the normal resting and the medulla oblongata. Despite this, physiologists
breathing pattern. still disagree about what the brainstem contains
• Science doesn’t have a good understanding of the control of
breathing. Reference: Note, Text pg. 309 50
 Neural Control: Maintaining Ventilatory Homeostasis
A rising level of CO2 in the blood, not a falling O2,
is the major stimulus that regulates
pulmonary ventilation in normal people.
• As the CO2 level in the blood increases,
normally during exercise or abnormally due to
hypoventilation, the pH of the cerebrospinal
fluid (CSF) is reduced.
– The pH of CHF (and indirectly the PCO2 of
the blood) is monitored by central
chemoreceptor cells located in the medulla
oblongata.
– The central chemoreceptors account for
about 70% of the response to CO2.
• As the CO2 rises, the medulla responds by
stimulating the motor nerves that control the
diaphragm and the intercostal muscles.
• The rate of cellular respiration(that is both the
oxygen consumption and carbon dioxide
production per minute) varies with the level of
activity.
– Exercise can increase tissue oxygen
demand (𝑉 O2) by 20-25 times.
– This is met by increasing the rate and
depth of breathing.

The normal neurological response to disturbances in ventilatory

homeostasis is a negative feedback process
Reference: Text pg. 221 (Fig. 10-11). 51
Cardiopulmonary Anatomy &
Physiology
RTT 100
Professor Michael Nazzaro
Supplement to Text, Chapter 9
The Respiratory System
You must study BOTH the chapter
and this supplement

Section 2g
The Airways

Reference: Text pg. 197-202

52
 Pulmonary Anatomy:
Most writers just say Upper and Lower Airways, with the
Essential Terms
glottis as the dividing line, but some use different terms,
including:
• Anatomically:
– Upper (Supraglottic), Middle, and Lower (distal) airways,
– Extrathoracic and Intrathoracic airways.
• Functionally:
• The Conditioning / Conducting Region Airways.
• The Exchange Region, also called:
– The Parenchymal Region.
– The Respiratory Region Airways.
• The text (pg. 195) states that the airways of the
tracheobronchial tree extend from the larynx down to the
airways participating in gas exchange [the lung parenchyma].
• Other writers mark the beginning of the lower respiratory tract
at the glottis.

• The upper airway (left), especially the nose

and nasopharynx conditions (warms, filters,
and humidifies) inspired air and reclaims heat
and moisture from expired air.
• The auditory tubes (eustacian tubes) drain
into the nasopharynx to the middle ear.
–The tubes allow air pressure to equalize on
both sides of the ear drum.
–Inflammation of the tubes can lead to otitis
media.

Reference, Text pg. 189-96 53

 The Upper Airway: The External Nose
• The nose is shaped like a pyramid.
• Its free angle is called the apex (L. tip).
• The lateral surface of the external nose ends in two
rounded, flared eminences called alae (L. wing),
–The alae nasi muscles flare the nostrils during
energetic breathing.
• The openings surrounded by the alae are the nares
(nostrils).
• The small diameter of the nares causes increased
frictional resistance to airflow.
– The nose provides a substantial amount of the
total airway resistance.
– Peak Inspiratory Flow Rate (PIFR) through the • Airflow resistance in the nose is about twice as high
nose is normally only about 1.5 - 2 milliliters per as through the mouth.
second (ml/s). (Poiseuille's Law, Text pg. 121, • The upper airway (nose to larynx) provides about 25 to
402). 40% of the total airway resistance.
• If thick secretions are present or more inspiratory effort • An Inspiratory flow rate of about 0.5 L/s, is ideal for
is exerted (such as during exercise): comfortable nasal breathing.
– Increased negative pressure tends to collapse the
nose despite its rigidity, •The bones and cartilages of the nose give it skeletal rigidity to resist
– Patients then begin to mouth breathe. collapse from subambient pressure during normal breathing.
•The upper 1/3 of the nose (the bridge) is formed by the R & L nasal bones
which articulate with the frontal process of the maxilla.
•The lower 2/3 consist of the lateral nasal cartilages, the two greater alar
cartilages, and the two lesser alar cartilages.
•The septal cartilage divides the nose into two approximately equal
chambers.
•The posterior 2/3 is lined with pseudostratified, ciliated, columnar epithelium
and mucous producing goblet cells.
– The cilia move the nasal mucous back toward the nasopharynx.

Reference: Note, Text pg. 189-194

54
 The Upper Airway: The Oral Cavity
• The mouth is the beginning of
the digestive tract, it is also an
auxiliary respiratory passage.
• The mouth is important in
digestion, breathing, speech, and
resistance to infection.
• The uvula contains nerve
endings that control the
pharyngeal reflex (the gag and
Pharyngeal swallowing reflex).
tonsils
(adenoids) are • The soft palate closes the
posterior and opening between the
superior to the nasopharynx and oropharynx
soft palate during swallowing, blowing,
sucking, and speech.
Airway Protective Reflexes:
1.Pharyngeal (causes
gaging & swallowing)
2.Laryngeal (adducts the
vocal cords)
3.Tracheal (causes
powerful, sustained
During forced or rapid breathing, the mouth is wide open coughing)
providing a large diameter airway opening. Resistance is 4.Carinal (causes powerful,
much lower than the nose, but the mouth has a much sustained coughing)
lower surface area to volume ratio (no turbinates) so it is
much less efficient as an HME (to warm, humidify, and
filter inspired air).
Reference: Note, Text pg. 191 55
 The Upper Airway: The Pharynx
• The pharynx (Gr. passage) or throat, is a The pharynx is a common passage for
somewhat funnel shaped tube about 13 food, liquids, and air
cm (5 inches) long in adults.
• The pharynx is usually described as
having three divisions:
1. The nasopharynx
– Posterior to the nasal cavity.
2. The oropharynx
– Posterior to the oral cavity.
3. The laryngopharynx
– Between the base of the tongue and
the esophageal opening,
– The laryngopharynx is sometimes
called the hypopharynx.
– The hypopharynx is the bottom of
the throat that connects the
oropharynx to the trachea and the
esophagus.
• The pharynx (all three divisions) starts at
the choanae and extends to the level of
the chricoid cartilage in the larynx.
• The pharynx is posterior to the nasal
cavity, the oral cavity, and the larynx.
• The pharynx is anterior to the cervical
vertebrae.
• During sleep, the muscle tone of the
upper airway structures including the
retropalatal (uvula and soft palate), and
hypopharynx relax leading to snoring
and obstructive sleep apnea (OSA).
Reference: Text pg. 191-94 56
The Upper / Lower Airway Division: The Larynx
The larynx consists of three single and three paired cartilages held together by ligaments,
membranes, and muscles.
• The three unpaired cartilages: the thyroid cartilage, the epiglottis, and the cricoid cartilage.
• The three smaller paired cartilages: the arytenoid, the corniculate, and the cuneiform
cartilages.
– The thyroid cartilage (Adam’s apple) is made of two fused plates of hyaline cartilage.
• The cricoid cartilage lies below the thyroid cartilage.
– The cricoid cartilage is the only complete tracheal ring.
– The cricoid is the narrowest point in the neonatal and younger child’s upper airway.
− The thyroid and cricoid are connected by the cricothyroid membrane.

Reference: Note, Text pg. 183, 192-93 57

Cardiopulmonary Anatomy &
Physiology
RTT 100
Professor Michael Nazzaro
Supplement to Text, Chapter 9
The Respiratory System
You must study BOTH the chapter
and this supplement

Section 2h
The Lower Airway

Reference: Text pg. 195-207

58
 The Lower Airway: The Tracheobronchial Tree
• The larynx is usually considered
the dividing line between the
upper and lower airways.
– After inspired air passes
through the larynx, it enters the
tracheobronchial tree.
• The tracheobronchial tree is a
series of branching tubes
(airways) that become
progressively smaller each time
they branch.
• Most writers identify 28
generations of branching airways
from the trachea (generation 0) to
the alveolar sacs (generation 28).
– Conducting airways extend
from generation 0, the trachea,
through generation 23, the
respiratory bronchioles.
– Gas exchange (Parenchymal Writers often refer to the lung and airway as the
tissue) begins at about the tracheobronchial tree. This reference is obvious
level of the respiratory when you look at the figure and imagine it as an
inverted tree:
bronchioles (generation 23)
and extends to the alveolar •The trachea is the trunk of the tree.
sacs (generation 28). •The bronchi are the branches.
•The alveoli are the leaves.
Reference, Text pg. 195-96 59
Tracheobronchial Tree: Divisions of the Airway

Reference: Note, Text pg. 195 (Fig. 9-42), 197 (Table 9-7), 200-01 (Fig. 9-94), 202 (Fig. 9-50). 60
 Tracheobronchial Tree: Histology of the Airway

Cartilaginous
airways

Non
cartilaginous
airways

Note how the “icicles” in the chart get thinner and end as points, indicating less of the tissue type at the
indicated location. The epithelial layer gets progressively thinner until it becomes the single cell layer of
the A/C membrane. Mucous secreting goblet cells are found down to the terminal bronchioles and
elastic fibers are found throughout the lung. Smooth muscle (controlled by the autonomic nervous
system) is present throughout most of the lung as well.
Reference: Note, Text pg. 198-99 (Fig. 9-47), 201 (Fig. 9-49) 61
 Tracheobronchial Tree: The Trachea
• The trachea is a cartilaginous and
membranous tube, extending from
the lower larynx at C6 to the upper
border of T5, where it divides into
right and left mainstem bronchi.
– The division is called the
tracheal carina (or just the
carina).
• The trachea is flattened
posteriorly.
• The adult trachea is about 11-13
cm long (Text says 12 cm), 1.5-2.5
cm (Text says 2 cm) in diameter.

The tracheal reflex is also a

vagovagal reflex. It causes a
violent cough when a foreign
object or irritation stimulates the
trachea.

The carinal reflex is another

vagovagal reflex. It causes a The right bronchus appears to be a more direct
powerful cough when the tracheal continuation of trachea. It is the site of most aspirated
carina is stimulated. foreign bodies. The trachea gets its blood supply from
the inferior thyroid arteries.
Reference: Note, Text pg. 195 62
Tracheobronchial Tree: Histology
• The epithelial lining contains
pseudostratified ciliated columnar
epithelial cells and mucous secreting
goblet cells.
– The columnar cells run from the
trachea down to the respiratory
bronchioles.
– The epithelial cells gradually grow
shorter and become cuboidal.
– Cilia and goblet cells disappear at
the level of the respiratory
bronchioles.
• A basement membrane separates the
epithelium from the lamina propria.
– The basement membrane
contains basal cells which replace
ciliated cells and goblet cells as
needed.
• The lamina propria contains
submucosal ducted mucous glands,
fibrous tissue, blood and lymph
vessels, branches of the vagus nerve
and two bands of smooth muscle that
wrap clockwise and counter clockwise
around the airway.
• The peribronchial sheath covers the
outer lamina propria.
• Goblet cells and mucous glands
produce about 100 ml/day of
pulmonary mucus in a normal, healthy
person.

Reference: Text pg. 200-01 (Fig. 9-48 & 49) 63

 Tracheobronchial Tree: Terminal Bronchioles
• The terminal bronchioles are the most distal segment of the conducting zone (they
start at about generation 16).
•Terminal bronchioles are a transition between the cuboidal epithelium of generation
15 and the squamous epithelium of generation 17.
– The airways from the nares to the terminal bronchioles make up the anatomic
dead space which is about 1ml/lb (Text says 2 ml/kg) of ideal or predicted
body weight (IBW or PBW). All airways distal to the terminal bronchioles are
part of the lung parenchyma.
• Terminal bronchioles have an average diameter of about 0.5mm (Text uses a
different number) and a total surface area of about 116 cm2.
•The terminal bronchioles lack goblet cells, submucosal glands and cilia.
– They contain Clara cells that secrete various substances including a surface-
active agent similar to surfactant.
• The lamina propria of the terminal bronchioles contains large amounts of smooth
muscle and elastic fibers.
– These smooth muscle cells contract and severely restrict air-flow during
asthmatic attacks
• Each terminal bronchiole supplies a cluster of respiratory bronchioles, called a
pulmonary lobule (aka the acinus, Gr for grape).
– The distance from the terminal bronchiole to the most distal alveoli is only
about 5mm.
Reference: Note,Text pg. 200
64
Tracheobronchial Tree: Terminal Bronchioles, Respiratory
Bronchioles, Alveolar Ducts & Sacs
• Terminal bronchiole are small, non-cartilaginous
airways < 1 mm in diameter.
• Respiratory bronchioles are smaller, < 0.5 mm
diameter, and branch off the terminal bronchioles.
– Some alveoli may appear on the respiratory
bronchioles.
• Alveolar ducts with continuous alveoli emerge from
the respiratory bronchioles.
− Alveolar ducts are elongated airways that have
almost no walls, only alveoli, as their peripheral
boundary.
− Rings of smooth muscle are present in the
interalveolar septa.
• Alveolar sacs surround the alveolar ducts.
− The surrounding alveoli open into these spaces.
− Alveolar sacs usually occur at the termination of
an alveolar duct but may occur anywhere along
the alveolar duct’s length.
• Alveoli are surrounded and separated from one
another by an exceedingly thin connective tissue
layer that contains blood capillaries.
− The tissue between adjacent alveolar air spaces
is called the alveolar septum or septal wall.

• The respiratory bronchioles, alveolar ducts, and

alveolar sacs that originate from a single terminal
bronchiole are called a primary lobule.
• Synonyms for primary lobule include terminal
respiratory unit, lung parenchyma, functional unit,
acinus, etc.
Note: Anatomically, the term acinus refers to the
smallest unit of a gland or a group of secretory
cells surrounding a cavity. Medical writers like to
use it instead of primary lobule because it
sounds Latin.

Reference: Text pg. 201 (Fig. 9-49) 65

Tracheobronchial Tree: Respiratory Bronchioles
• Respiratory bronchioles
have a diameter of < 0.5
mm (average about 0.4
mm) and a cross sectional
area of about 1000 cm2.
• They are formed of
squamous epithelia (some
writers say “low cuboidal”).
– They have occasional
alveoli budding from
their walls.
• Alveolar ducts originate
from the respiratory
bronchioles.
– They have an average
diameter of about 0.33
mm.
– The volume of the
respiratory zone
structures is about
3,000 mL
– The walls of the
alveolar ducts are made
up completely of alveoli.
• Each alveolar duct ends in
a cluster of alveoli (called
alveolar sacs). They are
the last generation of
airways.

Reference: Text pg. 197 66

 Tracheobronchial Tree: Alveolar Ducts & Sacs
The final two smallest
structures in the lungs:
• The Alveolar Duct,
(green arrow) which
connects the
Respiratory Bronchiole
to the Alveolar Sacs
(blue arrows) which are
the ends of the airways.
• If it looks like a sac
(like the ones in this
picture) you can safely
call it an alveolar sac.
• If it looks like it has
several sacs along it, it
is probably an alveolar
duct.
Green arrow - Alveolar Duct
Reference: Text pg. 203 (Fig 9-52) Blue arrow - Alveolar Sac 67
 Tracheobronchial Tree: Summary
Tracheobronchial
branches are
classified either as
segmental
bronchi or bronchioles:
Segmental bronchi
(cartilaginous airways)
1. Have connective tissue
coverings.
2. Are larger than 1 mm in
diameter.
Bronchioles
(non-cartilaginous
airways)
Divisions of the Airway: 1. Lack connective tissue
• 1 bronchi coverings.
• 2 bronchi 2. Are less than 1mm in
• 3 bronchi diameter.
• ~23 branches
The respiratory Zone starts at about
Generation 20-23 and ends at Generation
28 (the alveoli). 68
 Tracheobronchial Tree: Mucus Clearance
•The lining of the tracheobronchial tree
is composed of pseudostratified,
ciliated columnar epithelium, goblet
cells and glands that produce mucous
and serous (clear plasma) fluid.
• A mucus blanket (a viscoelastic gel)
on top of a watery sol layer sits on top
of the cilia.
– Pulmonary mucous is normally
about 95% water, plus proteins,
lipids, and other substances.
– In infection sputum changes its
color and viscosity as bacterial
and cellular DNA is added.
• The cilia move in a constant, beating
motion to clean the airways of foreign
bodies and inhaled organisms.
• The wave-like beating of the cilia
move the mucous toward the tracheal
carina.
• Coughing triggers a high-speed flow
of air that mobilizes the mucous
blanket.
High speed radiographic film of the mucocilliary
• Sputum contains mucous, nasal escalator (cilia and the mucous layer) moving
secretions, trapped particles and pulmonary secretions toward the pharynx.
saliva. Reference: Note, Text pg. 194-6 69
 Tracheobronchial Tree: Cilia & Clara Cells
Clara cells are non-mucous and non-
ciliated secretory cells located in the
bronchioles. Clara cells help to protect
the bronchiolar epithelium by:
1.Secreting a small variety of products
including Clara cell secretory protein
(CCSP), and a chemical component of
pulmonary surfactant.
2.Detoxifying harmful substances inhaled
into the lungs with the enzyme
Cytochrome P-450.
– Clara cells can also multiply and
differentiate into ciliated cells to help
regenerate damaged bronchiolar
epithelium.

Ciliated columnar epithelial cells.

Factoids about Cilia: Clara cells
• Each ciliated cell has about 200 cilia.
• Cilia are about 5-7 μm long.
• About 13-15 beats/sec.
The mucus blanket moves at about 21.5
mm/min. 70
Reference: Note, Text pg. 199-200 (Fig. 9-48).
Tracheobronchial Tree: Immune Response
Important Terms:
Antigen: (Specific)
chemical markers (protein
or oligosaccharide) on the
surface of cells. (General)
any substance that
stimulates an immune
response.
Immunogen - Any
substance that provokes
the immune response
when introduced into the
body. An immunogen is
always a macromolecule (a
protein or a
polysaccharide).
Allergen - A substance
that causes an allergic
reaction. It can do this if it
is ingested, inhaled,
injected or comes into
contact with the skin.

At first glance these terms

seem very similar. They are
not. They have significant
differences that you must be
aware of.

Reference: Text, pg. 199 71

 Tracheobronchial Tree: Immunoglobins
• The airway epithelial membranes rest
on basement membranes that contain
mast cells which are important in the
immune response.
• Immunoglobin E (IgE) is one of five
classes of immunoglobins made by
the human immune system
– The others are IgA, IgD, IgG and
IgM.
• The structure of IgA in
pulmonary secretions
(secretory IgA) is different
from that of circulating IgA.
• IgE is an antigen-specific
immunoglobin that interacts with mast
cells and eosiniphils to protect the
host against invading parasites.
• IgE is distributed throughout the body
with the following exceptions:
– IgE is not found in breast milk. Mast cell degranulation in response to exposure to an antigen
– Only small quantities are found in release preformed mediators (substances such as histamine) into
other secretions such as saliva. the blood. They cause the primary symptoms of allergies.
• The cells that synthesize IgE are Degranulation Processes
found predominantly in association 1 – Antigen.
with mucosal tissues (mucous 2 - IgE antibody.
membranes). 3 - FcεRI receptor (the high affinity receptor that binds tightly to
• Unfortunately, the same antibody-cell the antigen.
4 - Preformed mediators (histamine, proteases, chemokines,
combination is also responsible for heparin).
typical allergy or immediate 5 – Granules.
hypersensitivity reactions, such as 6 – The mast cell.
hay fever, asthma, hives and 7 - Newly formed mediators: (prostaglandins, leukotrienes,
anaphylaxis. thromboxanes, PAF).
72
Cardiopulmonary Anatomy &
Physiology
RTT 100
Professor Michael Nazzaro
Supplement to Text, Chapter 9
The Respiratory System
You must study BOTH the chapter
and this supplement

Section 2i
Sites of Gas Exchange

Reference: Text pg. 196-203

73
 Sites of Gas Exchange
• The respiratory zone (exchange zone)
begins at the respiratory bronchioles,
generations 20 to about 28.
–There are 3 generations of
respiratory bronchioles with alveoli
budding from their walls (see slides
117-119).
–There are 3 generations of alveolar
ducts made of alveoli separated by
septal walls that contain smooth
muscle.
–Each duct terminates in about 15-
20 alveolar sacs.
• The primary lobule contains the respiratory
bronchioles, the alveolar ducts, and
alveolar sacs.

Reference: Text pg. 200-06 74

 Sites of Gas Exchange: Alveolar Cell Types
• Type I alveolar pneumocytes
(squamous pneumocytes).
– They are wide and thin
(about 0.1 - 0.5 μ thick).
– They are the major sites of
gas exchange (about 95%
of gas exchange occurs
there).
• Type II pneumocytes stick out
of the alveolar wall into the air
space.
– They have microvilli and
produce pulmonary
surfactant.
• Type III pneumocytes are
alveolar macrophages, also
called dust cells.
– They are not part of the
alveolar wall.
– They migrate freely through
the alveolar spaces and the
interstitium.
– They remove foreign
material that reaches the
primary pulmonary lobule.
– Surfactant proteins (SP)
help regulate the immune
defensive function of the
Reference: Note ,Text pg. 204 (Fig. 9-54). alveolar macrophages. 75
 Sites of Gas Exchange: The Pores of Kohn
• The Pores of Kohn are small
openings in the alveolar septa
(between adjacent alveoli) within a
lobule of the lung (arrow).
– They are not sites of gas
exchange.
• The pores are about 10-14 μ in
diameter and are encircled by
elastic and reticular fibers.
• The Canals of Lambert are
another group of openings. They
connect alveoli to secondary
bronchioles.
• The pores and canals may be an
adaptation to permit collateral gas
flow to alveoli that have been
blocked by a proximal obstruction.
– They may provide some
collateral ventilation in lung
pathology (atelectasis and
asthmatic bronchoconstriction).
– They probably provide very
little collateral ventilation in
normal lungs.
– They do contribute to the
spread of bacterial infections
and cancer cells.
Lung section showing the Pores of Kohn

Reference: Note, Text pg. 202 76

Sites of Gas Exchange: AC Membrane

Reference: Note, Text pg. 106 (Fig. 0-56). 77