1. The Respiratory System
The Respiratory System
Functional Anatomy of the Respiratory System
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3. The Respiratory System
The Nose and Paranasal Sinuses
The nose provides an airway for respiration; moistens, warms, filters, and cleans incoming
air; provides a resonance chamber for speech; and houses olfactory receptors.
The nose is divided into the external nose, which is formed by hyaline cartilage and bones
of the skull, and the nasal cavity, which is entirely within the skull.
The nasal vestibule is lined with skin, contains sweat glands, sebaceous glands, and
hairs (vibrissae) which act as coarse filters to stop large particles from entering the nasal cavity.
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4. The Respiratory System
The nasal cavity contains two types of epithelium: olfactory mucosa (sensory receptors
for smell) and respiratory mucosa.
Respiratory mucosa:
pseudostratified ciliated columnar epithelium - cilia move mucus, cells contain defensins
(anti-bacterial chemicals)
goblet cells - secrete mucus, traps particles not filtered by nasal hairs (including bacteria)
sensory nerve endings - irritant receptors, trigger sneeze reflex
mucous glands - secrete mucus
serous glands - secrete watery serous fluid containing lysozyme; water humidifies air,
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5. The Respiratory System
lysozyme breaks down bacterial cell walls
rich capillary supply - warms air
Nasal conchae: 3 mucosa-covered projections from lateral wall of each nasal cavity
(superior, middle, and inferior).
Increase mucosal surface area, increase turbulence of inspired air, trap particulate
matter, warm and humidify inspired air. Also reclaim much heat and moisture from exhaled air.
The grooves inferior to each concha are nasal meatuses.
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6. The Respiratory System
The nasal cavity is surrounded by paranasal sinuses within the frontal, maxillary, sphenoid,
and ethmoid bones that serve to lighten the skull, warm and moisten air, produce mucus,
and act as resonance chambers for speech.
The Pharynx
The pharynx connects the nasal cavity and mouth superiorly to the larynx and
esophagus inferiorly.
The nasopharynx serves as only an air passageway, and contains the pharyngeal tonsil,
which traps and destroys airborne pathogens. The uvula is suspended from the
posterior aspect of the soft palate and moves superiorly during swallowing to prevent
passage of food and liquid into the nasopharynx.
The oropharynx is an air and food passageway that extends inferiorly from the level of the
soft palate to the epiglottis.
Epithelium changes to stratified squamous to resist friction of food passage.
The palatine tonsils are embedded in the lateral walls of the fauces (throat) and the
lingual tonsil is at the base of the tongue.
The laryngopharynx is an air and food passageway that lies directly posterior to the
epiglottis, extends to the larynx, and is continuous inferiorly with the esophagus.
The Larynx
The larynx attaches superiorly to the hyoid bone, opening into the laryngopharynx,
and attaches inferiorly to the trachea.
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8. The Respiratory System
The larynx provides an open airway, routes food and air into the proper passageways,
and produces sound through the vocal cords.
The larynx consists of hyaline cartilages: thyroid, cricoid, paired arytenoid, corniculate,
and cuneiform; and the epiglottis, which is elastic cartilage.
Vocal ligaments form the core of mucosal folds, the true vocal cords, which vibrate as
air passes over them to produce sound.
The vocal folds and the medial space between them are called the glottis.
Voice production involves the intermittent release of expired air and the opening and closing
of the glottis.
Valsalva’s maneuver is a behavior in which the glottis closes to prevent exhalation and
the abdominal muscles contract, causing intra-abdominal pressure to rise.
The trachea, or windpipe, descends from the larynx through the neck into the
mediastinum, where it terminates at the primary bronchi.
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9. The Respiratory System
The Bronchi and Subdivisions: The Bronchial Tree
The conducting zone consists of right and left primary bronchi that enter each lung and
diverge into secondary bronchi that serve each lobe of the lungs.
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10. The Respiratory System
Secondary bronchi branch into several orders of tertiary bronchi, which ultimately branch
into bronchioles.
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11. The Respiratory System
As the conducting airways become smaller, the supportive cartilage changes in character
until it is no longer present in the bronchioles.
The respiratory zone begins as the terminal bronchioles feed into respiratory bronchioles
that terminate in alveolar ducts within clusters of alveolar sacs, which consist of alveoli.
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12. The Respiratory System
Alveoli are surrounded by elastic fibers and an extensive network of capillaries. They
contain open alveolar pores to equalize pressure and have alveolar macrophages
to phagocytize particulate matter that may be drawn into the alveoli.
The respiratory membrane consists of a single layer of squamous epithelium, type-I
cells, surrounded by a basal lamina.
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13. The Respiratory System
Interspersed among the type-I cells are cuboidal type-II cells that secrete surfactant.
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14. The Respiratory System
The Lungs and Pleurae
The lungs occupy all of the thoracic cavity except for the mediastinum; each lung is
suspended within its own pleural cavity and connected to the mediastinum by vascular
and bronchial attachments called the lung root.
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16. The Respiratory System
Each lobe contains a number of bronchopulmonary segments, each served by its own
artery, vein, and tertiary bronchus.
Lung tissue consists largely of air spaces, with the balance of lung tissue, its stroma,
comprised mostly of elastic connective tissue.
There are two circulations that serve the lungs: the pulmonary network carries systemic
blood to the lungs for oxygenation, and the bronchial arteries provide systemic blood to
the lung tissue.
The lungs are innervated by parasympathetic and sympathetic motor fibers that constrict
or dilate the airways, as well as visceral sensory fibers.
The pleurae form a thin, double-layered serosa.
The parietal pleura covers the thoracic wall, superior face of the diaphragm, and
continues around the heart between the lungs.
The visceral pleura covers the external lung surface, following its contours and fissures.
Mechanics of Breathing
Pressure Relationships in the Thoracic Cavity
Intrapulmonary pressure is the pressure in the alveoli, which rises and falls during
respiration, but always eventually equalizes with atmospheric pressure.
Intrapleural pressure is the pressure in the pleural cavity. It also rises and falls
during respiration, but is always about 4 mm Hg less than intrapulmonary pressure.
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17. The Respiratory System
Pulmonary Ventilation: Inspiration and Expiration
Pulmonary ventilation is a mechanical process causing gas flow into and out of the
lungs according to volume changes in the thoracic cavity.
Boyle’s law states that at a constant temperature, the pressure of a gas varies inversely with
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18. The Respiratory System
its volume.
P1V1 = P2V2
During quiet inspiration, the diaphragm and intercostals contract, resulting in an increase
in thoracic volume, which causes intrapulmonary pressure to drop below atmospheric
pressure, and air flows into the lungs.
During forced inspiration, accessory muscles of the neck and thorax contract
(scalenes, sternocleidomastoid, pectoralis minor, erector spinae), increasing thoracic
volume beyond the increase in volume during quiet inspiration.
Quiet expiration is a passive process that relies mostly on elastic recoil of the lungs as
the thoracic muscles relax.
Forced expiration is an active process relying on contraction of internal intercostals
and abdominal muscles (oblique and transversus) to increase intra-abdominal pressure
and depress the ribcage.
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19. The Respiratory System
To use Boyle's law as an example, if we start with a lung volume of 2400 ml - V1 (the
functional residual capacity; see "Respiratory Volumes" below) and an intrapulmonary
pressure equal to atmospheric pressure (760 mm Hg - P1) and expand the thoracic cavity
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20. The Respiratory System
such that the lung volume reaches 2900 ml (a 500 ml breath - V2) we can see, according
to Boyle's law, that we would have a pressure gradient of 131mmHg.
Since gas flows from the area of higher pressure into the area of lower pressure, if
the epiglottis is open, the lungs inflate - voila, inspiration.
760 mmHg * 2400 ml = P2 * 2900 ml
( 760 mmHg * 2400 ml)/2900 ml = P2
629 mmHg = P2
∆P = 760 mmHg - 629 mmHg
∆P = 131 mmHg
It doesn't really work quite that way - as soon as the lung volume begins expanding
the pressure begins dropping and air begins flowing (from the area of higher pressure into
the area of lower pressure) so the pressure difference is really only about 1 mmHg until
it equalizes when inspiration stops.
(But we still get lung inflation.)
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21. The Respiratory System
Physical Factors Influencing Pulmonary Ventilation
Airway resistance is the friction encountered by air in the airways; gas flow is reduced
as airway resistance increases.
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22. The Respiratory System
Lung compliance is the degree of change in transpulmonary pressure required to cause
a change in lung volume.
Compliance primarily reflects the distensibility of lung tissue and alveolar surface
tension, although to be complete ease of expansion of the thoracic cage has to be taken
into consideration as well.
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23. The Respiratory System
Alveolar surface tension due to water in the alveoli acts to draw the walls of the
alveoli together, presenting a force that must be overcome in order to expand the lungs.
Distensibility of the lung depends on the amount of elastin present and the amount of
fibrosis present. (Of course a blocked airway will affect distensibility as well).
The ability to expand the thoracic cage can be affected by a number of things,
including thoracic deformities, calcification of costal cartilage, and interference with the
function of the diaphragm and/or intercostal muscles.
Respiratory Volumes and Pulmonary Function Tests
Respiratory volumes and specific combinations of volumes, called respiratory capacities,
are used to gain information about a person’s respiratory status.
Tidal volume is the amount of air that moves in and out of the lungs with each breath
during quiet breathing.
The inspiratory reserve volume is the amount of air that can be forcibly inspired beyond
the tidal volume.
The expiratory reserve volume is the amount of air that can be evacuated from the lungs
after tidal expiration.
Residual volume is the amount of air that remains in the lungs after maximal forced expiration.
Inspiratory capacity is the sum of tidal volume and inspiratory reserve volume, and
represents the total amount of air that can be inspired after a tidal expiration.
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24. The Respiratory System
Functional residual capacity is the combined residual volume and expiratory reserve
volume, and represents the amount of air that remains in the lungs after a tidal expiration.
Vital capacity is the sum of tidal volume, inspiratory reserve and expiratory reserve
volumes, and is the total amount of exchangeable air.
Total lung capacity is the sum of all lung volumes.
The anatomical dead space is the volume of the conducting zone conduits, which is a
volume that never contributes to gas exchange in the lungs.
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25. The Respiratory System
Pulmonary function tests evaluate losses in respiratory function using a spirometer
to distinguish between obstructive and restrictive pulmonary disorders.
The FVC, or forced vital capacity, is the vital capacity measured while forcefully exhaling.
The FVC should be the same as the VC, but the test is done to collect data on the rate
of exhalation.
The FEV, or forced expiratory volume, is the amount of air expelled during specific
time intervals of the FVC. Under normal conditions the FEV should be 80% of the FVC in
the 1st second.
Obstructive disorders, like chronic bronchitis, result in increased airway resistance. It would
be likely to see increased TLC, FRC, and RV due to hyperinflation of the lung. The FEV
would be less than 80% in the 1st second of the FVC.
Restrictive disorders, tuberculosis or fibrosis cause a decrease in total lung capacity.
There would be decreases in VC, TLC, FRC, and RV. The FEV would be greater than 80%
in the 1st second but the FVC (like the VC) would be reduced.
Alveolar Ventilation
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26. The Respiratory System
The MVR (minute ventilation rate), or the amount of air entering and leaving the lungs in
one minute (RR * TV) doesn't really tell you much about effective ventilation, that is, the
amount of air actually available to participate in gas exchange.
The alveolar ventilation rate (AVR) takes dead space into account - RR*(TV - DSV) - and
gives a better measure of usable air.
Nonrespiratory air movements cause movement of air into or out of the lungs, but are
not related to breathing (coughing, sneezing, crying, laughing, hiccups, and yawning).
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27. The Respiratory System
Gas Exchanges Between the Blood, Lungs, and Tissues
Basic Properties of Gases
Dalton’s Law of Partial Pressures
Dalton’s law of partial pressures states that the total pressure exerted by a mixture of gases
is the sum of the pressures exerted by each gas in the mixture, and the pressure exerted
by each gas (its partial pressure) is proportional to the percentage of that gas in the mixture.
Henry’s Law
Henry’s law states that when a mixture of gases is in contact with a liquid, each gas
will dissolve in the liquid in proportion to its partial pressure. Of course the solubility of the
gas has something to do with how well that actually goes (and there is a temperature effect
as well - gases are less soluble at higher temperatures than lower temperatures).
O2 is 1/20 as soluble in liquid as CO2 and nitrogen is even less, about 1/40 as soluble as
CO2 - meaning very little nitrogen can enter circulation at normal pressures.
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28. The Respiratory System
Composition of Alveolar Gas
The composition of alveolar gas differs significantly from atmospheric gas, due to
gas exchange occurring in the lungs, humidification of air by conducting passages, and
mixing of alveolar gas that occurs with each breath.
External Respiration: Pulmonary Gas Exchange
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29. The Respiratory System
External respiration involves O2 uptake and CO2 unloading from hemoglobin in red blood cells.
Three factors influence movement of gases across the respiratory membrane:
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30. The Respiratory System
1. Partial Pressure Gradients and Gas Solubilities
A steep partial pressure gradient (PO2 alv = 104 mm Hg, PO2 cap = 40 mm Hg)
exists between blood in the pulmonary arteries and alveoli, and O2 diffuses rapidly from
the alveoli into the blood.
Equilibrium between alveolar PO2 and capillary PO2 is reached before the blood is 1/3 of
the way through the capillary.
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31. The Respiratory System
Carbon dioxide moves in the opposite direction along a partial pressure gradient that is
much less steep; PCO2 cap = 45 mm Hg, PCO2 alv = 40 mm Hg.
The difference in the degree of the partial pressure gradients of oxygen and carbon
dioxide reflects the fact that carbon dioxide is much more soluble than oxygen in the blood.
2. Ventilation-Perfusion Coupling
Ventilation-perfusion coupling ensures a close match between the amount of gas reaching
the alveoli and the blood flow in the pulmonary capillaries.
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32. The Respiratory System
3. Thickness and Surface Area of the Respiratory Membrane
The respiratory membrane is normally very thin, and presents a huge surface area for
efficient gas exchange.
Internal Respiration: Capillary Gas Exchange in the Body Tissues
The diffusion gradients for oxygen and carbon dioxide are reversed from those for
external respiration and pulmonary gas exchange.
The partial pressure of oxygen in the tissues is always lower than the blood, so oxygen
diffuses readily into the tissues, while a similar but less dramatic gradient exists in the
reverse direction for carbon dioxide.
Transport of Respiratory Gases by Blood
Oxygen Transport
Since molecular oxygen is poorly soluble in the blood, only 1.5% is dissolved in plasma,
while the remaining 98.5% must be carried on hemoglobin.
Association of Oxygen and Hemoglobin
Up to four oxygen molecules can be reversibly bound to a molecule of hemoglobin—
one oxygen on each iron.
Oxyhemoglobin is written HbO2, deoxyhemoglobin, or reduced hemoglobin, is written
HHb. Oxygenation of hemoglobin occurs in the lungs and oxygen unloading occurs in
the tissues.
Lungs
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33. The Respiratory System
HHb + O2 HbO2 + H+
Tissues
Hemoglobin has a "high affinity" structure, in which oxygen is bound tightly, and a "low
affinity" structure which binds oxygen less tightly and releases it more easily.
The affinity of hemoglobin for oxygen increases with each successive oxygen that is bound
and decreases with each oxygen released, making oxygen loading and unloading very efficient.
At higher plasma partial pressures of oxygen, hemoglobin unloads little oxygen, but if
plasma partial pressure falls dramatically, i.e. during vigorous exercise, much more oxygen
can be unloaded to the tissues.
Temperature, blood pH, PCO2, and the amount of BPG in the blood all influence
hemoglobin saturation at a given partial pressure.
Influence of PO2 on Hemoglobin Saturation
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34. The Respiratory System
The PO2 gradient required to unload one oxygen from fully saturated HbO2 is 60 mm Hg.
The PO2 gradient required to unload one oxygen from partially saturated HbO2 is
substantially less, and decreases with each successive oxygen removed.
Influence of Other Factors on Hemoglobin Saturation
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35. The Respiratory System
Temperature: increased temperature, a by-product of increased metabolic activity, pushes
Hb from its high affinity structure toward its low affinity structure, from which oxygen
unloads more easily.
Increased temperature also increases the metabolic rate of RBCs, increasing the production
of BPG, which also facilitates oxygen unloading from HbO2.
pH: Lower pH (increased H+ concentration) favors oxygen unloading from HbO2 because H
+ ion binding to the protein portion of Hb stabilizes the low affinity structure of Hb.
Oxygen saturation of HbO2inhibits H+ ion binding to Hb but metabolically active
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36. The Respiratory System
tissues generate enough H+ ions to overcome the inhibition .
As H+ ions bind to Hb, the affinity for O2 decreases; as O2 is released from Hb H+ ions
can more easily bind, which further facilitates the release of O2.
In the lungs the increased PO2 favors oxygen binding to HHb, which drives H+ ions off Hb
and into solution and increases the affinity of Hb for O2; the complete oxygen saturation
of HbO2 achieved in the lungs stabilizes the high affinity structure of Hb.
This interaction, which facilitates oxygen unloading where it is needed and oxygen
loading where it is plentiful, is known as the Bohr effect.
PCO2: Increased blood PCO2, the result of metabolic activity of tissues, decreases the
affinity of Hb for oxygen and facilitates oxygen unloading. The mechanisms of the
interaction will be discussed in the context of CO2 transport in the blood.
BPG: A by product of glycolysis in RBCs, BPG binds to Hb and stabilizes the low
affinity structure.
The Hemoglobin-Nitric Oxide Partnership in Gas Exchange
Nitric oxide (NO), secreted by lung and vascular endothelial cells, is carried on hemoglobin
to the tissues where it causes vasodilation and enhances oxygen transfer to the tissues.
Carbon Dioxide Transport
Carbon dioxide is transported in the blood in three ways: 7–10% is dissolved in plasma, 20%
is carried on hemoglobin bound to globins, and 70% exists as bicarbonate, an important
buffer of blood pH.
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38. The Respiratory System
The Haldane effect encourages CO2 exchange in the lungs and tissues: when plasma
partial pressure of oxygen and oxygen saturation of hemoglobin decrease, more CO2 can
be carried in the blood.
The carbonic acid–bicarbonate buffer system of the blood is formed when CO2 combines
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39. The Respiratory System
with water and dissociates, producing carbonic acid and bicarbonate ions that can release
or absorb hydrogen ions.
Control of Respiration
Neural Mechanisms and Generation of Breathing Rhythm
The medulla oblongata contains the ventral respiratory group, or inspiratory center,
with neurons that act as the pacesetting respiratory group (inspiratory and expiratory,
influence each other), and the dorsal respiratory group, which functions mostly as
an integrative center for inputs from peripheral stretch and chemoreceptors.
The pontine respiratory group within the pons modifies the breathing rhythm and
prevents overinflation of the lungs through an inhibitory action on the medullary
respiration centers.
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40. The Respiratory System
It is likely that reciprocal inhibition on the part of the different respiratory centers is
responsible for the rhythm of breathing.
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41. The Respiratory System
Factors Influencing Breathing Rate and Depth
The most important factors influencing breathing rate and depth are changing levels of
CO2, O2, and H+ in arterial blood.
The receptors monitoring fluctuations in these parameters are the central chemoreceptors
in the medulla oblongata, and the peripheral chemoreceptors in the aortic arch and
carotid arteries.
Increases in arterial PCO2 cause CO2 levels to rise in the cerebrospinal fluid, resulting
in stimulation of the central chemoreceptors, and ultimately leading to an increase in rate
and depth of breathing.
Substantial drops in arterial PO2 are required to cause changes in respiration rate and
depth, due to the large reserves of O2 carried on the hemoglobin.
As H+ accumulates in the plasma, rate and depth of breathing increase in an attempt
to eliminate carbonic acid from the blood through the loss of CO2 in the lungs.
Higher brain centers alter rate and depth of respiration.
The limbic system, strong emotions, and pain activate the hypothalamus, which
modifies respiratory rate and depth.
The cerebral cortex can exert voluntary control over respiration by bypassing medullary
centers and directly stimulating the respiratory muscles.
Pulmonary irritant reflexes respond to inhaled irritants in the nasal passages or trachea
by causing reflexive bronchoconstriction in the respiratory airways.
The inflation, or Hering-Breuer, reflex is activated by stretch receptors in the visceral
pleurae and conducting airways, protecting the lungs from overexpansion by
inhibiting inspiration.
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Peripheral chemoreceptor locations
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44. The Respiratory System
Respiratory Adjustments
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Adjustments During Exercise
During vigorous exercise, deeper and more vigorous respirations, called hyperpnea,
ensure that tissue demands for oxygen are met.
Three neural factors contribute to the change in respiration: psychic stimuli, cortical
stimulation of skeletal muscles and respiratory centers, and excitatory impulses to
the respiratory areas from active muscles, tendons, and joints.
Adjustments at High Altitude
Acute mountain sickness (AMS) may result from a rapid transition from sea level to
altitudes above 8000 feet.
A long-term change from sea level to high altitudes results in acclimatization of the
body, including an increase in ventilation rate, lower than normal hemoglobin saturation,
and increased production of erythropoietin.
Homeostatic Imbalances of the Respiratory System
Chronic obstructive pulmonary diseases (COPD) are seen in patients
that have a history of smoking, and result in progressive dyspnea,
coughing and frequent pulmonary infections, and respiratory failure.
Obstructive emphysema is characterized by permanently enlarged alveoli and deterioration
of alveolar walls, collapse of bronchioles during expiration (increasing resistance and
trapping air), and damage to pulmonary capillaries, causing increased resistance and
leading to right side congestive heart failure.
Chronic bronchitis results in excessive mucus production, as well as inflammation and
fibrosis of the lower respiratory mucosa.
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Asthma is characterized by coughing, dyspnea, wheezing, and chest tightness, brought on
by active inflammation of the airways.
Tuberculosis (TB) is an infectious disease caused by the bacterium
Mycobacterium tuberculosis and spread by coughing and inhalation.
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47. The Respiratory System
Lung Cancer
In both sexes, lung cancer is the most common type of malignancy, and is strongly
correlated with smoking.
Squamous cell carcinoma arises in the epithelium of the bronchi, and tends to form
masses that hollow out and bleed.
Adenocarcinoma originates in peripheral lung areas as nodules that develop from
bronchial glands and alveolar cells.
Small cell carcinoma contains lymphocyte-like cells that form clusters within the
mediastinum and rapidly metastasize.
Developmental Aspects of the Respiratory System
By the fourth week of development, the olfactory placodes are present and give rise to
olfactory pits that form the nasal cavities.
The nasal cavity extends posteriorly to join the foregut, which gives rise to an outpocketing
that becomes the pharyngeal mucosa.
By the eighth week of development, mesoderm forms the walls of the respiratory
passageways and stroma of the lungs.
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48. The Respiratory System
As a fetus, the lungs are filled with fluid, and vascular shunts are present that divert blood
away from the lungs; at birth, the fluid drains away, and rising plasma PCO2
stimulates respiratory centers.
Respiratory rate is highest in newborns, and gradually declines to adulthood; in old
age, respiratory rate increases again.
As we age, the thoracic wall becomes more rigid, the lungs lose elasticity, and the amount
of oxygen we can use during aerobic respiration decreases.
The number of mucus glands and blood flow in the nasal mucosa decline with age, as
does ciliary action of the mucosa, and macrophage activity.
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