3/9/2022

The Respiratory System

Herdiantri Sufriyana

Previous key points to remember

• Glomerular filtration rate and conditions that affect it
• Na+ reabsorption
• RAAS, ANP, and antihypertensive drugs
• Glucose reabsorption and diabetes mellitus
• PO43- and Ca2+ reabsorption and parathyroid hormone
• BUN, creatinine, and uric acid
• H+, K+, and organic ion secretion
• Plasma inulin and PAH clearance
• Countercurrent multiplication and vasopressin for H2O regulation and
renal failure
• Micturition and urinary incontinence

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The respiratory
• Atmosphere and alveoli system
Ventilation • Mechanical act
• Adjust the flow of air

• Alveoli and pulmonary

Diffusion capillaries
• O2 and CO2 exchange The circulatory
system

• Lungs and tissues

Transportation • Blood transports O2 and
CO2

External
Respiration • Systemic (tissue) capillaries
Perfusion and tissue cells
• O2 and CO2 exchange

• Use 2 and produce

Cellular
Respiration
CO2
Respiration
• Within mitochondria

Nonrespiratory functions of the respiratory

system

Acid-base balance by
Heat eliminator and altering the amount of Enabling vocalization
Respiratory pump
breathing air humidifier H+-generating CO2 (speech, singing, etc.)
exhaled

Defending against inhaled
foreign matter
Removing, modifying,
activating, or inactivating
various materials, e.g.: Smelling by nose (a part
• Prostaglandins inactivation
of the respiratory system)
(preventing systemic effects)

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Respiratory airways
• Nose and mouth  pharynx 
esophagus and larynx 
trachea  bronchi 
bronchioles  alveoli
• Vocal folds + laryngeal muscles
 opening = glottis  sound 
lips + tongue  sound patterns
• Glottis is closed when
swallowing

Alveoli
• Fick’s law of diffusion:
• Shorter distance  greater rate of
diffusion
• 0.5 µm
• Tracing paper is 50 x thicker
• Greater surface area  greater rate
of diffusion
• 500 millions alveoli of 300 µm in
diameter
• 75 m2 (a tennis court) vs. 0.01 m2 (if
a single hollow chamber)
• 95% type-I alveolar cells
• 5% type-II alveolar cells
(pulmonary surfactant) within the
lumen
• Alveolar macrophages (within the
lumen

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Lungs
• Several lobes
• Each supplied by a bronchus
• Changing thoracic cavity to inflate and
deflate alveoli in lungs
• Thoracic wall: 12 pairs of curved ribs,
sternum, thoracic vertebrae, thoracic
skeletal muscles, diaphragm
• A pleural sac separates each lung from
the thoracic wall
• The picture is exaggerated
• Pleural cavity  intrapleural fluid
• Parietal and visceral pleura
• Clinical note: pleurisy, an inflammation of
pleural sac  painful breathing  friction
rub  lung inflation/deflation

• From higher to lower pressure, or down a pressure

gradient
Respiratory • Three pressures in ventilation
mechanics • Atmospheric (barometric) pressure  diminishes with increasing
altitude and fluctuates at any altitude because of weather
conditions
• Intra-alveolar pressure  air flows down the pressure gradient
equilibrating the atmospheric and alveoli pressures whenever
these are different
• Intrapleural pressure  does not equilibrate because of no
openings

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Transmural pressure gradient

• Normally stretches alveoli walls
• 760 – 756 = 4 mm Hg pushing
outward
• Trans = across; mural = wall
• Lungs follow the movements of the
chest wall
• Intrapleural pressure is
subatmospheric because of fluid
• Transmural pressure gradient 
stretches lungs  pull away from
thoracic wall  intrapleural fluid
cannot expand  pressure drop 
transmural pressure gradient

Clinical note: pneumothorax

• Intrapleural and intra-alveolar
pressures are equilibrated  no
transmural pressure gradient 
unstretched  lung collapse
• e.g.:
• Traumatic pneumothorax
• A stab wound
• A broken rib
• Spontaneous pneumothorax
• A disease process

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Boyle’s law
•𝑃𝑉 =𝑃 𝑉
• At any constant temperature, the
pressure exerted by a gas in a
closed container varies inversely
with the volume of the gas
• Increasing gas volume 
decreasing gas pressure
• Changing thoracic cavity volume +
transmural pressure gradient =
changing lung (intra-alveolar)
volume  changing intra-alveolar
pressure  air low into or out of
the lungs

Inspiratory and expiratory muscles

• Inspiration (inhale)
• Quite inspiration
• Forced inspiration
• Expiration (exhale)
• Passive expiration
• Active expiration

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Quite inspiration
• Major inspiratory muscles:
• Diaphragm (75% quite inspiration)
• External intercostal muscles (25% quite
inspiration  pull the ribs upward and
outward
• Diaphragm descends 1 to 10 cm
• Lung expansion  759 mm Hg  air
flows into the lungs  760 mm Hg
• Lung expansion is not caused by the
air flow; instead, the air flow is
caused by the lung expansion
• Intrapleural pressure  754 mm Hg

Forced inspiration
• Accessory inspiratory muscles:
• Sternocleidomastoid muscles
• Scalenus muscles
• Raises sternum and elevates the
first two ribs
• Deeper breath

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Passive expiration
• Diaphragm and external
intercostal relaxation
• Lung recoil  761 mm Hg
 air flows out of the
lungs  760 mm Hg
• Intrapleural pressure 
756 mm Hg

Active expiration
• Abdominal muscles 
increases intra-abdominal
pressure  upward force on
the diaphragm
• Internal intercostal muscles
 pull the ribs downward
and inward

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Wrap-up respiratory cycle

Airway resistance

𝐹 = ∆𝑃/𝑅
Sympathetic and
Parasympathetic stimulation
epinephrine stimulation 
 bronchiolar smooth
• 𝐹 is airflow rate muscle contraction 
bronchiolar smooth muscle
relaxation 
bronchoconstriction 
• ∆𝑃 is atmosphere- increases airway resistance
bronchodilation 
decreases airway resistance
alveoli pressure gradient
• 𝑅 is resistance of
airways, determined by Clinical note: epinephrine or
albuterol
their radius

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Clinical note: chronic obstructive pulmonary

disease (COPD)
• More difficult on expiration than
Chronic inspiration
bronchitis
A group of lung • Wheezing
diseases characterized
by increased airway
resistance resulting
from narrowing the
airway
Asthma

Emphysema

Clinical note: chronic bronchitis

Frequent exposure to irritating:

• Cigarette smoke
• Polluted air
• Allergens

Prolonged edematous thickening of the airway linings + overproduction of

mucus

Irritants immobilize the ciliary mucus escalator  mucus is excellent

medium of pulmonary bacterial growth  infection

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Clinical note: asthma

• Thickening of airway walls  inflammation + histamine-induced edema
• Excessive secretion of thick mucus
• Airway hyperresponsiveness  constriction in the smaller airways 
trigger-induced spasm
• Triggers, repeated exposure to:
• Allergens (e.g. dust mites or pollen)
• Irritants (e.g. cigarette smoke)
• Respiratory infections
• Vigorous exercise
• The most common chronic childhood disease

Clinical note: emphysema

• Collapse of the smaller airways
• Breakdown of alveolar walls
• Caused by:
• Trypsin (protein digesting enzyme)  macrophages  cigarette smoke or
other irritants
• α1-antitrypsin  inhibits trypsin
• Chronic irritation  overwhelm α1-antitrypsin  also destroy lung tissue
• Genetic inability to produce α1-antitrypsin  unprotected lung tissue 
small amount of macrophage-released enzymes without irritants

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Pulmonary elasticity
Compliance Elastic recoil
• Pulmonary surfactant
• Lipids and proteins
• Change in lung • Lung rebound after • Secreted by type-II alveolar cells
volume given stretched • Interspere among water molecules 
change in reducing cohesive forces
• Two factors: • Increases compliance
transmural pressure • Elastic connective • Reduces elastic recoil
gradient tissue
• Clinical note: • Alveolar surface
pulmonary fibrosis tension 
 normal lung cohesive forces
tissue  fibrous among the
connective tissue  molecules (H2O >
chronic exposure of pulmonary
asbestos fibers or surfactant)
similar irritants

Clinical note: newborn respiratory distress

syndrome
Fetal lungs  late pregnancy  pulmonary Surfactant
surfactant synthesis
replacement
Premature infant  insufficient pulmonary
therapy
surfactant  strenuous inspiration +
completely-collapsed alveoli during expiration
• Greater transmural pressure gradient needed
• Up to 20 to 30 vs. 4 to 6 mm Hg
Drugs can hasten
surfactant-
Newborn respiratory muscles is still weakly
contracted
secreting cells
maturation

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Lung volumes and capacities

• Male 5.7 L and female 4.2 L
• Small airways collapse before lungs are completely deflated,
blocking further outflow
• Male 1.2 L and female 1.0 L
• Diminishing fluctuation of blood O2 and CO2
• Less effort to inflate a partially deflated than a totally collapsed
one
• Spirometer, spirogram
• Volumes (young adult male):
• Tidal volume (TV; 500 ml)  quite inspiration and passive
expiration
• Inspiratory reserve volume (IRV; 3000 ml)  forced inspiration
• Expiratory reserve volume (ERV; 1000 ml)  active expiration
• Residual volume (RV; 1200 ml)  remaining air after maximum
expiration  measured by gas-dilution techniques (e.g. helium)
• Capacity  sum of >1 volumes
• Inspiratory capacity (IC) = IRV + TV
• Functional residual capacity (FRC) = ERV + RV
• Vital capacity (VC) = IRV + TV + ERV
• Total lun capacity (TLC) = VC + RV
• Forced expiratory volume in 1 second (FEV1)  80% VC in
the 1st sec.

Clinical note: respiratory

dysfunction
• Obstructive  difficulty in lung emptying
• Reduced ERV
• Reduced FEV1
• Restrictive  difficulty in lung filling
• Reduced IC
• Others:
• Diseases impairing diffusion across the pulmonary
membranes
• Reduced ventiolation because of mechanical failure (e.g.
neuromuscular disorders affecting respiratory muscles)
• Inadequate perfusion
• Ventilation-perfusion imbalances
• Measurements: spirometry, x-ray examination, blood-
gas tests, tests to measure the diffusion capacity of
the alveolar capillary membrane (e.g. diffusing
capacity of carbon monoxide; DLCO)

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Anatomic dead space

• 𝑃𝑢𝑙𝑚𝑜𝑛𝑎𝑟𝑦 𝑣𝑒𝑛𝑡𝑖𝑙𝑎𝑡𝑖𝑜𝑛 (𝑚𝑙/
𝑚𝑖𝑛) = 𝑇𝑉(𝑚𝑙/𝑥) × 𝑅𝑅(𝑥/𝑚𝑖𝑛)
• 6000 = 500 × 12
• Up to 150,000 (25 x)
• Higher TV is better than higher RR
because of dead space
• 150 ml remains in the conducting
airways  anatomic dead space
• Only 350 ml are exchanged in
alveoli

Alveolar ventilation
• 𝐴𝑙𝑣𝑒𝑜𝑙𝑎𝑟 𝑣𝑒𝑛𝑡𝑖𝑙𝑎𝑡𝑖𝑜𝑛 = 𝑇𝑉 − 𝑑𝑒𝑎𝑑 𝑠𝑝𝑎𝑐𝑒 × 𝑅𝑅
• 4200 = (500 – 150) x 12

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Partial pressure of a gas

• Atmospheric pressure is the sum of
pressures by each gas
• A molecule of any gas exerts the
same amount of pressure
• The pressure is proportional to the
gas proportion
• Partial pressure is a pressure
contributed by a gas (many
molecules)
• PO2 is 160 mm Hg (21% of 760 mm
Hg)
• PCO2 is 0.23 mm Hg

Partial pressure
gradient
• Humidified air  add more H2O
• Dead space not included
• Thus:
• Atmospheric PO2 is 160 mm Hg
• Atmospheric PCO2 is 0.23 mm Hg
• Alveolar PO2 is 100 mm Hg
• Alveolar PCO2 is 40 mm Hg
• Blood PO2 is 40 mm Hg
• Blood PCO2 is 46 mm Hg
• Other factors (Fick’s law), clinical note:
• Emphysema
• Pulmonary edema  pulmonary inflammation
or left-sided CHF
• Pulmonary fibrosis  thick fibrous tissue
• Pneumonia  inflammatory fluid accumulation
• Depending on the rate of cellular
metabolism

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O2-Hb dissociation (or saturation) curve

• O2 bound to Hb does not
contribute to the PO2 of the blood
• 𝐻𝑏 + 𝑂 ⇌ 𝐻𝑏𝑂
• Hb is reduced Hb or deoxyHb
• HbO2 is oxyHb
• 4 O2 per Hb (bound to heme
portion, which is 4 Fe2+)
• Law of mass action:
• If the concentration of one
substance involved in a reversible
reaction is increased, the reaction is
driven toward the opposite side
• 60 to 100 mm Hg is the plateau
portion of the curve
• 100 mm Hg PO2  97.5% SatO2
• 60 mm Hg PO2  90% SatO2
• At high altitude or O2-deprived
chamber at sea level  unless <60
mm Hg, near-normal amounts of O2
can still be carried
• Clinical note:
• Pulmonary diseases with
inadequate ventilation or
defective gas exchange
• Circulatory disorders with
inadequate blood flow to
the lungs
• 0 to 60 mm Hg is the steep
portion of the curve
• 40 mm Hg PO2  75% Sat
O2
• Metabolizing more actively
 e.g. 40 to 20 mm Hg 
75 to 30%  45%
• While at rest  e.g. 100 to
40 mm Hg  97.5 to 75%
 ~25%
• Thus, giving progressively
larger free O2 up tp 85% of
those bound to Hb when
actively metabolizing

Role of Hb in gas exchange

• O2 diffuses in lungs and tissues to
equilibrate
• When O2 bound to Hb, the
gradient is rebuild
• The diffusion continues until no
longer O2 bound or released
respectively in lungs and tissues
• Thus, transport more O2 than
would be possible without Hb
• Clinical note: if severe anemia, in
which Hb levels fall to 50%, then
O2 transport falls by 50% although
the arterial PO2 is 100 mm Hg
with 97.5% SatO2

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Hb-O2 affinity (bond strength)

• Factors: CO2, acidity, temperature, and 2,3-
biphosphoglycerate (BPG)
• At tissue level  shift to right  less SatO2 given the
same PO2  more O2 released
• Anaerobic metabolism  carbonic and lactic acids 
more O2 released  aerobic metabolism
• Active metabolism  higher CO2, acidity, and temperature
• At pulmonary level  shift to left  more SatO2
given the same PO2  more O2 bound
• 2,3-BPG bound to Hb in red blood cells  increases to
help maintain free O2 availability  chronic
undersaturation: high altitudes, circulatory or
respiratory diseases, anemia
• Clinical note: 240 x higher affinity to CO than that to
O2  HbCO (carboxyHb)  burning of gasoline, coal,
wood, and tobacco  no sensation of breathlessness

CO2 transport
• 10% physically dissolved
• 30% bound to globin portion of Hb
(carbaminoHb or HbCO2)
• More affinity to CO2 than O2
• O2 unloading helps
• 60% as bicarbonate:
• Slowly in plasma
• 𝐶𝑂 + 𝐻 𝑂 ⇌ 𝐻 𝐶𝑂 ⇌ 𝐻 + 𝐻𝐶𝑂
• Swiftly in the red blood cells by
carbonic anhydrase (ca)
• 𝐶𝑂 + 𝐻 𝑂 𝐻 + 𝐻𝐶𝑂
• More affinity to H+ than O2
• O2 unloading helps

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• Hypoxia:
• Hypoxic hypoxia: low arterial PO2,
low Hb saturation
• Normal alveolar PO2, low arterial
PO2
• Exposure to high altitude or others
where atmospheric PO2 is reduced
 low alveolar and arterial PO2
• Anemic hypoxia: reduced O2-
carrying capacity of the blood
• Causes:
• Reduced red blood cells
• Reduced Hb in red blood cells
• CO poisoning
• Normal arterial PO2, low O2
content of the arterial blood
• Circulatory hypoxia: too little
oxygenated blood to the tissues
• Local vascular blockage
• General circulation: congestive
heart failure or circulatory shock
• Normal arterial PO2, normal O2
content of the arterial blood
• Histotoxic hypoxia: the cells cannot
used the O2
• Cyanide poisoning  cyanide
blocks cellular respiratory enzymes
Clinical note:
• Hyperoxia: only when using
supplemental O2  oxygen toxicity  abnormal arterial
brain damage, blindness-causing
damage to the retina PO2 and PCO2
• Hypercapnia: having excess CO2 in
arterial blood
• Caused by hypoventilation  most lung
diseases
• Hypocapnia: below-normal arterial
PCO2
• Increased ventilation is not
hyperventilation if matching metabolic
needs, or hyperpnea, as in exercise
• Caused by hyperventilation  anxiety
states, fever, aspirin poisoning
• Most Hb fully saturated by CO2; thus,
no additional O2 is added to the blood
albeit fully-supplemented
• Effect of reduced O2 is apparent,
while abnormal CO2 is less obvious
• Abnormal CO2 affects acid-base
balance  respiratory acidosis and
alkalosis

Control of respiration
• Unconscious, but the pacemaker
resides in the respiratory control
centers in the brain (not in the
lungs or respiratory muscles, as in
the heart)
• Unlike cardiac activity, respiratory
activity is also subject to voluntary
control
• Controlling factors for:
• Alternate rhythm
• Rate and depth of breathing
• Respiratory activity supporting other
purposes (e.g. speech, cough, sneeze)

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Medullary respiratory center
Dorsal respiratory group
(DRG)
• Inspiratory neurons
• Firing  quite inspiration
• Firing cessation  quite
expiration
• The pacemaker is pre-
Bötzinger complex
Pneumotaxic and apneustic centers
Pneumotaxic center
stimulates DRG to switch
off inspiratory neurons,
limiting the duration
Pneumotaxic > apneustic
3/9/2022
Ventral respiratory group
(VRG)
• Inspiratory neurons 
forced inspiration
• Expiratory neurons 
active expiration
• DRG stimulates VRG to rev
up respiratory activity
Apneustic center prevents
inspiratory neurons being
switched off, extending the
duration
Clinical note: without
pneumotaxic  prolonged
with brief expiration 
apneusis  certain types of
severe brain damage
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Hering-Breuer reflex

Prevent
overinflation
Inhibit inspiratory
neurons

Afferent nerves

Pulmonary stretch
receptors within
the smooth
muscles of the
airways are
stretched

Control of ventilation
• Three chemical factors:
• PO2
• PCO2
• H+
• Peripheral chemoreceptors:
• Carotid bodies
• Aortic bodies
• Decreased PO2 if <60 mm Hg
• Severe pulmonary disease
• Reduced atmospheric PO2
• The plateau portion helps
• Clinical note: anemia or CO poisoning  PO2 is still normal
• PCO2  min-to-min regulation
• Mainly by central chemoreceptors
• Only by CO2-generated H+ in brain ECF
• At 70-80 mm Hg, it depresses respiration and produce
severe respiratory acidosis
• H+  non-CO2-generated H+ stimulates peripheral
chemoreceptors
• Central chemoreceptors is less sensitive during sleep 
apnea (spontaneous resume) 1-2 mins for 500 x per night

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Clinical note: sudden infant death syndrome

• 2-to-4 months old infants
• Unknown etiology
• Some cases  abnormal lung development
• Risk factors:
• Sleeping position (on abdomen; 40%)
• Exposure to nicotine during fetal life or after birth (3 x more likely)

Key points to remember

• Transmural pressure gradient
• Lung volumes and capacities (obstructive vs. restrictive)
• Alveolar ventilation
• Hb-O2 dissociation curve (what to shift)
• Abnormal PO2 and PCO2
• Control of respiration

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