L21-28 Respiratory System
Tuesday, May 19, 2015
7:59 AM
I suggest watching his videos for Example Questions and explanations
External respiration
- Airflow into lungs = ventilation
- Gas exchange via diffusion
- Blood flow through PULOMNARY capillaries is driven by concentration of RV
Structure of the Respiratory System
Respiratory system is divided into 2 by upper (nasal cavity/mouth) and lower respiratory system
(Trachea -> alveolar sacs)
Forces involved in ventilation
- At Rest, Diaphragm is relaxed -> no bulk flow
○ PAlveoli=PBarometric
- Inspiration, diaphragm contracts and intrathoracic volume increases
○ PAlveoli<PBarometric
- Expiration, Diaphragm relaxes and intrathroacic volume decreases
○ PAlveoli>PBarometric
Intrapleural space
- Pleural sac forms double membrane surrounding lung
- Air-water surface tension reduces friction between lungs and helps produce pressure
○ Negative Pressure (think of it as a "sucking"/"attracting" force)
 The Negative pressure within pleural space helps pull IN chest wall (which naturally
wants to expand) and helps EXPAND lungs (which naturally want to collapse)
○ Functional Residual capacity = when Chest wall's desire to expand = Lungs desire to
collapse -> volume of air in lungs when forces are at equilibrium
 Is actually the Residual volume in lungs (volume remaining after maximal expiration) +
the volume for forced expiration
- CLINICAL
○ Pneumothorax
 Opening in pleural membrane allows pressure within the pleural space to equalize
from -5 to 0 -> negative pressure is destroyed => Lungs collapse and chest wall
expands
Muscles for inspiration
- Diaphragm is most important inspiratory muscle
- External intercostals and accessory muscles -> prevent ribs from being pulled down during
contraction
Muscles for Expiration
- Normally is a PASSIVE process caused by relaxing diaphragm
○ Elastance of lungs and chest wall are primary forces of expiration
○ During quiet inspiration, normal lungs store energy in elastic recoil to fuel quiet
expiration (PASSIVE)
- Forced expiration performed by Abdominal muscles and internal intercostals
Lung Compliance
Physio Page 1
- FRC (Functional Residual capacity) is the volume of air in lungs when forces are at equilibrium
○ Chest want to expand and lungs want to collapse => Forces are equal and pressure is 0
(Expanding forces are completely opposed to collapsing forces)
- When FRC = 0, the "distance" to + pressure amount in lungs is = to - pressure amount
in chest wall
- Yellow line -> As the airway pressure increases (fills the lungs), the lung expands and want to
collapse "more" thus the collapsing force on the lungs increases
- Blue line -> At FRC, negative pressure in chest cavity compresses chest wall which increases the
expanding force on the chest wall (b/c it wants to be expanded)
○ Chest wall pressure is 0 when it is where it wants to be
○ As pressure becomes positive, the chest wall is expanded past where it wants to be and
begins to feel collapsing forces
- During expiration -> lungs are smaller (thus want to collapse “less”) and Chest is retracted and
wants to expand more => Net forces are directed outwards
○ You go down on the yellow line towards 0 airway pressure -> Blue line moves further left ->
more expanding force
- During inspiration -> Lungs are expanded and want to collapse more and chest is expanded (wants
to expand “less”) => Net forces directed inwards
○ As you go up on the blue line during inspiration, the yellow line moves more right-> more
collapsing force
- CLINICAL
○ Lung disease effects lung compliance (not chest wall)
○ Emphysema
- Destructive lung disease which damages walls between alveoli leading to irreversible
airflow obstruction -> LUNGS LOSE ELASTICITY and breathing OUT
- becomes more difficult as air remains trapped in overinflated lungs
□ See SOB, Coughing, Wheezing, Slight Hypoxemia (Pink Puffers), BARREL CHEST,
increased risk of Cor Pulmonale
- Loss of elastic fibers => MORE compliant => easier to get air in but no elasticity to help
get air out
- Expanding forces are much higher -> volume increases (Barrel chest)
- FRC is HIGHER and HIGHER intrapleural pressure and transmural pressure will be 0
before all air is expired (meets equal pressure point)
○ Fibrosis -> replace elastin with collagen => LESS compliant => harder to get air in
- Collapsing forces are higher -> Lower volume
- FRC is LOWER
Physio Page 2
- FRC is LOWER
- Factors affecting LUNG Compliance
○ Elastin and collagen fibers of lung
○ Surface tension
- Von Neergaard experiment showed that lungs filled with liquid had more compliance
and recoiled solely due to elastic fibers whereas the lungs filled with air had less
compliance and recoiled solely due to surface tension
- Surface tension accounts for 1/2 of elastic recoil in lungs -> water in the alveoli want
to collapse the alveoli so due to increase in surface tension (attraction between water
molecules)
□ Inspiration requires the air to OVERCOME attractive forces between water ->
expiration due to recoil pressure from the surface tension
- This is why it is important to have SURFACTANT
□ Surfactant REDUCES surface tension by disrupting forces between liquid
molecules thus INCREASES compliance
□ Important because lungs have different sized alveoli
 Smaller alveoli have decreased radius => increased Pressure => increase
tendency to collapse (water molecules are closer together and are
attracting across the space)
 Larger alveoli have increase radius => decreased pressure => decreased
tendency to collapse
 Since alveoli are connected, the increased pressure in the smaller alveoli
will cause air to prefer the large alveoli -> small alveoli will collapse
making it harder to expand for next inspiration
 Surfactant lining the small alveoli will be closer together and cause greater
decrease surface tension (compared to larger alveoli) -> less pressure ->
less tendency to collapse
□ Functions of Surfactant
 Promotes alveolar stability
 Prevent Atelectasis
 Reduces inflation pressure (via increased compliance)
 Decrease work of breathing
Work of Breathing
- Inspiration
○ 65% of the work is Elastic
- Lung's Elastic recoil -> must overcome the lung's tendency to collapse
- Chest wall recoil -> chest wall assists expansion to a point
- Surface forces -> surfactant helps counteract surface tension
○ 35% of the work is non-elastic
- Tissue resistance (20%) -> obesity/pregnancy pressing against expansion of chest
cavity
- Airway resistance (80%) -> constriction of bronchi or nares
□ Remember, air moves due to PRESSURE GRADIENT
□ Resistance increases initially at mid-sized bronchioles (as diameter decrease is
larger than the number of branches) and then decreases as you go further into
lungs (similar to resistance in capillaries)
 Proximal Large airways have low cross-sectional diameter -> High air
velocity -> More turbulent flow => Lung sounds
 Distal small airways (bronchioles) have LARGE cross-sectional diameter
(but small individual diameter)-> LOW velocity => helps diffusion of
gasses (Call "silent zone")**
◊ Hearing sounds in smaller airways is BAD
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Physiologic factors affecting airway resistance
- Increase airway resistance
○ Parasympathetic -> Constrict bronchioles => Use anticholinergic to block beta receptors
○ Smooth muscle
○ Alpha-adrenergic receptors
○ Mucus secretion
○ Histamines, Leukotrienes, and PGs
○ Irritants (smoke, dust)
○ Edema
○ Airway inflammation
○ Decreased Airway CO2
- Decrease Airway resistance
○ Sympathetic -> Dilates bronchioles -> use Beta2 agonist to activate dilations
- Airway resistance distribution in Tracheobronchial tree determined by 2 things
○ Airways are mechanically tethered to the alveoli that surround them, thus as you INSPIRE ->
airways dilate and resistance DROPS due to Radial Traction thus RESISTANCE IS HIGHEST AT
LOW LUNG VOLUMES and vice versa
- Radial traction helps keep airways open during inspiration AND expiration
□ Lack of radial traction during expiration is why patients with emphysema cannot
expire as well
○ Transmural/Transpulmonary Pressure is Pressure in Small airways (Intra-alveolar pressure) Pressure outside the airway (Intra-pleural Pressure) = The pressure that holds alveoli open
- At end of Expiration, Transmural pressure = 0 - -5 = +5 -> Transmural pressure is +5 =>
Pressure holds alveoli open
- At end of Inspiration, Transmural pressure = 0 - -6 = +6 -> Transmural pressure is +6
=> Pressure holds alveoli open better than during expiration
□ The intrapleural pressure becomes more negative with inspiration -> Pulls
alveoli open more
○ Because of Radial Traction and Transmural Pressure keeping alveoli open at high lung
volumes, the alveoli do NOT collapse during deep breathing even with high expiratory
efforts
- If you breathe in less air, then alveoli can collapse if you have high expiratory effort
□ You get Effort Independent expiratory flow which is No change in flow despite
increased flow effort because the high effort collapses alveoli
□ TL;DR - High Lung Volume = greater radial traction/transmural pressure forces
to keep alveoli open even against high expiratory forces; Lower volume = lower
forces to help keep alveoli open
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Physiological Dead space
- Is the area in the lungs that have volume but do not have gas exchange
- Functional Alveolar Dead Space
○ Impaired perfusion in ventilated alveoli leading to V-! Mismatch and wasted ventilations
- Anatomic Dead Space
○ Internal volume of ALL CONDUCTING (non-gas exchanging) airways from nose to mouth to
respiratory bronchioles (usually ~150 ml)
○ Fresh air travels through dead space and "pushes" this "mixed air" into lungs so if you take
in 450 mL of FRESH air, only 300 mL of it actually fills lungs (because 150 is dead space air)
- This is why initially PO2 within alveoli decreases before increasing and PCO2 increases
before decreasing
○ When you expire, the FRESH AIR that remained in the dead space is expired and conducting
airways are filled with "mixed" alveolar air
- PCO2 increases as you expire the O2 out of the alveoli and the CO2 leaves your
capillaries and enters into alveoli
□ O2 ENTERS ALVEOLI FROM INSPIRATION; CO2 ENTERS VIA BLOOD THROUGH
METABOLISM -> this is why PCO2 increases when holding breath
- WATCH HIS VIDEO FOR ANIMATION
○ Anatomic Dead space is measured by recording the amount of O2 expired before Nitrogen is
expired -> O2 was in dead space and Nitro is expired from alveoli
Ventilation
- Ventilation is the volume of air moved in/out of lungs over time (Volume/Time)
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- Ventilation is the volume of air moved in/out of lungs over time (Volume/Time)
- Normal Tidal Volume (Vt) = 500 ml/Min
○ Amount of air inspired/expired with each normal breath (air through mouth/nose)
- Respiratory rate = 12-15 breaths/min
- Normal Minute Ventilation = 6 L/min
○ Minute Ventilation (Ve) is volume ventilated in minute = Tidal Volume x Rate
- Alveolar Ventilation (Va)
○ Only accounts for air that is undergoing gas exchange (NOT dead space)
○ Va = (Tidal Volume - Dead space) x Rate
- Functional RESIDUAL Capacity (Residual Volume)
○ Volume that remains in lungs after maximal expiration (~2300-3000 mL) -> important for
Buffering extreme changes in PA and provides longer ability to hold breath during special
activities (diving, instruments, etc)
○ COMPLIANCE of lungs is HIGHEST (work of breathing minimized) while Pulmonary
VASCULAR RESISTANCE is Lowest (optimal blood flow) -> cannot be measured via
spirometry
- Emphysema (obstructive) spirometry curve
○ Unlike the equal slope for inspiration and expiration on normal breathing, emphysema
patients show normal slope for inspiration but less steep expiration curve because they
have trouble expiring due to collapsed airway
- Flow During Forced Expiration test (FEF25-75) will show a DECREASED slope because it
takes longer to get air out (flow is decreased)
○ Residual volume also decreases thus FRC also increases while ERV decreases -> increases
total lung capacity
○ Normal patients will also expire entire vital capacity in 3 seconds; HOWEVER, takes much
longer in emphysema patients (~6 seconds)
- Emphysema patients will also have lower FEV1:FVC ratios
- Restrictive spirometry curve
○ Caused by disease that restrict expansion of lungs but do not affect airway resistance
○ All spirometry values are REDUCED
○ Patients with restrictive diseases will expire vital capacity in 3 seconds or even sooner
because they cannot take as much air in
- They may also have higher FEV1:FVC ratio (> or equal to 0.8)
Ideal Alveolar Gas Equation
- Used to predict Alveolar O2 pressure based on Alveolar CO2 pressure
○ This is possible because normal barometric pressure of atmospheric air is 760 mmHg with
160 mmHg O2, 600 mmHg Nitrogen, and 0 mmHg CO2
Physio Page 6
160 mmHg O2, 600 mmHg Nitrogen, and 0 mmHg CO2
Hyperventilation vs Hypoventilation
- Hyperventilation = breath more => breath more O2 in and CO2 out -> PaO2 increases and PaCO2
decreases (in the blood)
○ Ventilation exceeds metabolic production of CO2
- Hypoventilation = breath less => breath less O2 in and less CO2 out -> PaO2 decreases and PaCO2
increases
○ Inadequate ventilation relative to metabolic production of CO2
○ Will lead to CEREBRAL VASODILATION -> want to increase ventilation to expire more CO
Regional Differences in ventilation
- Gravity also plays a role in ventilation -> easier ventilation in Lower lung zones while upper zones
have less ventilation
○ The alveoli at the Apex of the lungs are stretched maximally and do not have further
compliance thus have limited ventilation capacity
○ Alveoli at the base have highest ventilation because they have ability to increase compliance
by expanding
Non-respiratory functions of lungs
- Olfaction
- Processing of inhaled air
○ Warming -> gasses dissolve better in warm environment
○ Water vapor -> prevents alveoli from drying out
○ Filtration with mucus/cilia
- Cilia move the trapped substances upwards towards pharynx for expiring/swallowing
- CLINICAL
□ Cystic Fibrosis is condition with altered CTFR gene which means impaired
transport of Chloride ions into mucus layer -> Na+ is not retained in the mucus
layer due to lack of Cl- -> Na moves into cell and water follows -> Mucus
becomes very thick
□ Airways are clogged with mucus and infective agents are not move out
□ Symptoms: Fibrosis of lungs, "Salty skin", Productive Cough, Chest infections
- Filters small emboli from blood
○ Including blood clot, fats, air bubbles, cancer cells
• Biochemical reactions
○ Removal of Serotonin, Bradykinin, leukotrienes
○ Conversion of Ang1 -> Ang2 by ACE
Perfusion
• Lungs receive entire cardiac output of Right Ventricle -> HIGH flow; LOW pressure/resistance
Pulmonary Vascular resistance = (Input Pressure - Out Pressure)/Blood flow
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○ Pulmonary Vascular resistance = (Input Pressure - Out Pressure)/Blood flow
○ Very important for pressure and resistance to be low -> prevents capillary rupture and
pulmonary edema
- Remember that along entire length of pulmonary capillary, pressure is low -> favors
fluid reabsorption into capillary (thus gasses dissolved in fluid also absorbed)
Intrapulmonary circulation occurs from TWO different supplies
○ Pulmonary arteries carry majority of blood supply and has deoxygenated-mixed blood -> gas
exchange in alveoli and return to heart as pulmonary veins
○ Bronchial arteries carry oxygenated blood from aorta to conducting airways (DO NOT
participate in gas exchange)
- Return and 2/3 drain into Pulmonary Vein (going back to heart) while 1/3 drain into
Azygos system/Intercostals (to Right atrium)
Gravity affects pulmonary blood flow similarly to ventilation (blood flow is higher in base than
apex)
○ For most of the lung, blood flow is higher than ventilation
○ However, at around 3rd rib, blood flow decreases below ventilation (V/Q ratio is much
higher)
Regulation of Pulmonary blood flow
○ Hypoxic Pulmonary Vasoconstriction
- Hypoxic alveoli causes vasoconstriction to divert blood flow to better ventilated
alveoli
- Motor innervation also plays a role in vasoconstriction
- In high altitude locations, many alveoli are hypoxic thus there is more
vasoconstriction -> increased pulmonary arterial pressure -> increased capillary
filtration => Edema
□ Also increases workload of Right heart => hypertrophy
○ Passive factors include Recruitment and Distension
- Pulmonary resistance decreases with increase in blood flow and pressure due to
RECRUITMENT -> more alveolar vessels are open to help with increased flow/pressure
- DISTENSION also occurs to help create WIDER vessels
- These passive factors allow lungs to accommodate a lot of blood flow (such as during
exercise) without much increase in pressure
□ However, there is a limit to the ability of these passive factors thus increased
Left atrial pressure leads to pulmonary edema as capillary hydrostatic pressure
exceeds oncotic pressure and lymphatic capacity
 Increased capillary hydrostatic pressure due to MI, Mitral Stenosis,
Pulmonary Veno-occlusive disease, fluid overload
 Decreased Oncotic Pressure due to hypoalbuminemia, renal disease (loss
of proteins
 Increased capillary permeability due to toxins, radiation, ARDS, O2-toxicity
 Lymphatic Insufficiency due to increased central lymphatic pressure or
lymphangitis carcinomatosa
Diversity of Pulmonary Vessels
○ Extraalveolar
 Include the arteries, arterioles, vein, and venules outside of the alveolar wall ->
affected by intrapleural and interstitial pressure NOT alveolar pressure
□ Inspiration increases transpulmonary pressure which causes DILATION of
extraalveolar capillaries via radial traction
□ Thus, pulmonary vascular resistance in Extraalveolar vessels are highest during
EXPIRATION (or when air volume is closer to Residual volume)
○ Alveolar
 Capillaries within alveolar wall
 Alveolar stretch and pressure affect the diameter of alveolar vessels
□ Inspiration causes alveoli to stretch outwards and COMPRESS alveolar capillaries
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□ Inspiration causes alveoli to stretch outwards and COMPRESS alveolar capillaries
□ Thus, pulmonary vascular resistance in alveolar vessels are highest during
INSPIRATION (or when air volume is closer to total lung capacity)
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CLINICAL
○ Pulmonary HTN = Pulmonary artery systolic >30 and Mean Pulmonary arterial Pressure >20
 Precedes COR PULMONALE (RV enlargement) => RV failure
 Primary - etiology is unknown, generally due to anatomical changes
 Secondary HTN can be caused by respiratory disease, cardiac failure, or renal failure
Matching Ventilation and Perfusion
• Ventilation (V) is measured as the frequency of breathing x volume of each breath
• Perfusion (Q) depends on blood flow -> gas content in blood equilibrates with gas in alveoli
• Ideally V/Q = 1 but in reality is about 0.8 (Ratio drops if decrease ventilation/increase perfusion)
○ Since ratio is 0.8 you have lack of V/Q overlap in some places
 Arterial hypoxemia = Good blood flow but no ventilation (PO2 decreases)
□ VQ ratio DECREASES
□ Occurs due to some form of a shunt
 Intrapulmonary = block of air due to disease, etc
 Anatomic = when venous blood from lungs dumps into pulmonary veins
 Alveolar dead space = Ventilation but no blood flow (PO2 normal due to
recruitment/dilation of lung vessels)
□ VQ ratio INCREASES
• V/Q ratio is higher at top of lungs than at bottom of lungs because base of lungs get significantly
more blood flow than apex
○ Arterial PO2 at top of lung is close to 140; However, average PO2 of arterial blood is 100
because Lung units at bottom of lung contribute more to PO2 because that’s where
perfusion is the greatest (PO2 and PCO2 is inversely releated)
• Defects in Ventilation-Perfusion
○ Dead space -> no perfusion
○ High V/Q (emphysema) -> High ventilation/O2 in alveoli and low blood flow/CO2 from
blood -> Arterial values have high PO2 and Low PCO2
○ Low V/Q (restrictive dz) -> Low ventilation/O2 in alveoli and high blood flow/CO2 from
blood -> Arterial values will match
○ Shunt (no ventilation) -> Blood PO2/PCO2 levels are the same as they are in Pulmonary
arteries (PO2 = 40; PCO2 = 45)
Blood-Gas Exchange
• Alveoli are small, thin-walled sacs that are surrounded by capillaries and provide thin
barrier/surface area for gas exchange
• Alveoli are lined with 2 types of epithelium
○ Type 1 cells: Site for gas exchange -> account for 95% of alveolar surface
 No muscle fibers and blood vessels fill 85% of space between alveoli
○ Type 2 cells: Synthesize and secrete surfactant
• Gases move between air and blood by passive diffusion based on Partial PRESSURE GRADIENT
○ Only DISSOLVED O2 is considered when calculating PO2 however, most of the O2 in blood is
taken up by RBC (Hb) -> Increases gradient to increase O2 uptake into blood
○ Remember that diffusion is also determined by Molecular properties (solubility) and
membrane area/permeability
○ Pulmonary Diffusion Capacity (DL) helps assess transfer rate of gases = CONDUCTANCE
 DL encompasses the Gas diffusion coefficient, surface area, membrane thickness, and
time required for gas to combine with Hb
 DL = Ventilation/(Gas pressure in alveoli - Gas pressure in capillary)
 Use CO to determined DL
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 Use CO to determined DL
□ CO has 200x affinity for Hb than O2 thus assume all CO is bound to Hb (Pressure
in capillary = 0) -> DL for CO equation now = Ventilation / Pressure in alveoli
□ Inhale small CO -> 10 seconds -> measure exhaled CO => if values is less than 25
= diffusion problem
• TOTAL gas concentration is sum of Dissolved gas, Hb-Bound gas, and chemically modified gas
(such as bicarbonate)
○ Perfusion-Limited transport
 Substances cross capillary barrier without issues -> FLOW dependent
 N20 dissolves very well in blood (doesn’t bind to Hb) and will saturate blood very
quickly, thus diffusion is dependent on blood flowing past alveoli to maintain gradient
□ Once it saturates blood at beginning of capillary, diffusion stops so alveolar
pressure increases
○ Diffusion-limited transport
 Substances that have difficulty crossing barriers -> distance dependent
 CO binds to Hb so does not matter if blood is flowing as long as RBC are available for
binding however, does not cross barrier well so it depends on factors that mediate
diffusion
Under normal conditions, O2 is PERFUSION LIMITED (similar to N2O) thus increasing
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○ Under normal conditions, O2 is PERFUSION LIMITED (similar to N2O) thus increasing
perfusion increases O2 transport
 Note: Not as steep as N2O because O2 that is dissolving in blood is taken up by Hb
thus, it takes longer for PaO2 to equilibrate (since only dissolved = PaO2)
 With exercise, the graph is even less steep so perfusion may never reach maximum
 With fibrosis, the graph may never reach maximum due to diffusion issue and
ventilation issue. Similarly, Emphysema leads to diffusion issue due to destruction of
alveolar wall and Pulmonary edema leads to diffusion issue due to increase in
diffusion distance
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