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Pulmonary Ventilation
Pulmonary Functions
Conducting Airways
• Lead inspired air to gas exchanging
regions
• Anatomic dead space – 150 ml
– Nose
– Mouth
• Process by which ambient air moves into
and exchanges with the air in the lungs
Conducting Airways
– Trachea
• Add H2O vapor to inspired air
• Warm air to body temperature (sometimes cooling)
• Trap particulate matter and fumes to prevent them from
reaching the alveolar membranes
–
–
–
–
–
Dust
Yeast
Bacteria
Smoke
Ozone
– Right and left main bronchi
– Bronchioles
– Terminal bronchioles
1
Respiratory Zone
• Where gas exchange occurs
• 2.5 – 3 L
Respiratory Zone
• Provides a large surface area for gas
exchange
– Respiratory bronchiole
• Occasional alveoli budding from walls
– Alveolar ducts
• Lined with alveoli
The Lungs
•
•
•
•
Gas exchange – O2 and CO2
Volume = 4-6 L
Weight = 1 kg
Vascularized with infoldings which provide
a high surface area for blood aeration
• Rest – RBC remains in pulmonary capillary
for .5 – 1 sec only
• >300 million alveoli
Alveoli
• Sacs ~ 0.3 mm in diameter
• Alveolar tissue receives the largest blood
supply of any of the body’s organs
• Very thin pulmonary blood-gas barrier
• Each minute – 250 mL O2 leave alveoli and
enter blood - 25 X during
2
Minimum of distance and tissue
between alveolar air and RBC’s
Ventilation
• Caused by changes in thoracic volume
which results in intrapulmonary pressure
changes
Movement of Air
• Airflow (L/min) = pressure gradient (mm Hg)/resistance
• Resistance – sum of forces opposing flow of gas
– 20% - tissue friction during inspiration and expiration
– 80% due to friction between gas molecules and walls of airway
and internal friction between gas molecules themselves
• Pressure gradient > Resistance to obtain flow
• Boyle’s Law – pressure of a gas in inversely related to its
volume under constant temperature
Diaphragm
• Primary ventilatory muscle
• Creates an airtight separation between
abdominal and thoracic cavities with
openings for esophagus, vessels, and nerves
• Greatest capacity of all respiratory muscles
for shortening and volume displacement
Mechanics of Ventilation
• Inspiration – chest cavity increases
– Ribs move up and out – external intercostals lift ribs up
and away from body
– Floor of thorax descends - diaphragm contracts (up to
10 cm)
– Volume is increased, intrapulmonary pressure
decreases below ambient/atmospheric conditions
– Atmospheric air rushes into lungs
• 70% of lung expansion from A-P enlargement
• 30% of lung expansion from diaphragmatic descent
– Inspiration ends when thoracic cavity expansion ceases,
causing intrapulmonary pressure to increase to ambient
pressure
3
Inspiration
• As air moves into the smaller branches of
the lungs, the increase in surface area
significantly slows airflow into alveoli
Mechanics of Ventilation
• Expiration – passive at rest
– Natural recoil of stretched lung tissue
– Relaxation of respiratory muscles
–
–
–
–
Diaphragm and external intercostals relax
Diaphragm recoils raising floor of thorax
Ribs return to original position
Decreases the volume of thorax, increasing
intrapulmonary pressure
– Air rushes out of lungs
– Expiration ends when intrapulmonary pressure
decreases to atmospheric pressure
Ventilation During Exercise
• Expiration – active movement results in more
rapid and extensive exhalation
• Internal intercostals pull ribs down and in
• Abdominals contract to increase abdominal
pressure forcing diaphragm up into thorax
• Muscle involvement greatly increases maximal
rate of ventilatory flow
• During exercise, tidal volume (VT) increases more
than breathing frequency (f) which provides
sufficient time for gas exchange in the alveoli
4
Surface Tension
• Early physiologists found that lungs inflated with
saline have more compliance (easier to distend)
than air-filled lungs
• Surface tension relates to the resistance created at
the lining of the alveoli where a liquid contacts a
gas
• Surface tension is the force acting across an
imaginary line 1 cm long
• Surface tension in the alveoli during inspiration
increases resistance
Surface Tension
• Attractive forces between adjacent molecules of
the liquid are much stronger than those between
the liquid and gas
– LaPlace’s Law: pressure = 4 X surface tension/radius
• Pressure difference across the alveolar wall will be
greater for alveoli with smaller radii for a given
surface tension
• Smaller alveoli would generate more pressure than
a larger alveoli and would tend to empty into
larger alveoli
Surfactant to the Rescue
• Surfactant is secreted by some of the
alveolar epithelial cells
• Synthesized in lungs from FA
• Surfactant decreases surface tension in
small alveoli more than large alveoli to
eliminate the pressure difference
Sphere has smallest SA for a given volume
Advantages of Surfactant
• A low surface tension in alveoli increases lung
compliance and reduces work of expanding lungs
• Alveoli are more stable – small do not empty into
large alveoli
• Helps keep alveoli dry
– As surface tension forces tend to collapse the alveoli,
they tend to suck fluid into the alveolar spaces from
capillaries
5
Respiratory Zone Functions
•
•
•
•
Surfactant production
Endocrine functions
Molecule activation and inactivation
Blood clotting regulation
Fick’s law
• Gas diffuses through a sheet of tissue at a
rate…
– Directly proportional to tissue area (diffusion
constant)
– Directly proportional to pressure differential of
gas on each side of membrane
– Inversely proportional to tissue thickness
– CO2 diffuses 20X faster than oxygen due to
higher solubility of CO2
Gas Exchange
• Body’s supply of oxygen depends on…
– Concentration
• 20.93% oxygen
• 79.04% nitrogen
• 0.03% carbon dioxide
Diffusion
• Primary means for gas movement and
distribution
• Gas pressures rapidly equilibrate on each
side of the alveolar-capillary membrane
• Fick’s law – governs gas diffusion through
the alveolar membrane
Pressure Changes
• Pressure differential between air in lungs and
lung-chest wall interface causes lungs to adhere to
chest wall
• Any change in thoracic cavity volume alters lung
volume
• Important as lungs contain no skeletal muscles to
alter their volume
***Multimuscle respiratory pump system alters the
volume of the lungs during inspiration and
expiration
Gas Exchange
– Pressure in ambient air
• Mixture of gases, total pressure exerted by gases is
sum of the pressure of individual gases making up
the mixture
– Pressure is standardized to sea-level
• Barometric pressure of 760 mm Hg
• Above sea-level, barometric pressure is measured
(PB)
– PG is the portion of total pressure exerted by any single gas
within the mixture and proportional to its percentage in the
total gas mixture (Dalton’s law of partial pressures)
6
Partial Pressure
•PG = PB X FG
• Partial pressure of a gas (mm Hg) = total pressure
(mm Hg) X fraction of the gas
• PG = PB X FG
• Note that as air enters the nasal cavities it
completely saturates with water vapor, diluting the
inspired mixture
• At body temperature (37° C) water pressure is 47
mm Hg (760 – 47 = 713 mm Hg)
• Effective PO2 = .2093 X 713 = 149 mm Hg
• Humidification little effect on inspired PCO2
Alveolar Air
Henry’s Law
• CO2 enters alveoli from blood and O2
leaves lungs and enters blood
• Gases diffuse from high pressure to low pressure
• Rate of diffusion depends on…
– Pressure difference between gas above the fluid and the
gas dissolved in the fluid
– Solubility of gas in the fluid
• Quantity of Gas in a Fluid
= Solubility Coefficient X (PG/total barometric pressure)
Body
• Dissolved O2 ~ 4% total oxygen consumed
by body each minute at rest and <2% during
maximal exercise
For every unit of pressure favoring diffusion, ~ 25X more
carbon dioxide than oxygen moves into/from a fluid
7
Gas Exchange in Lungs
• Pressure gradients for gas transfer at rest
– Oxygen - 60 mm Hg
– Carbon dioxide – 6 mm Hg
• Transfers rapidly due to solubility
– Nitrogen – not used or produced in metabolic reactions
so essentially unchanged
– Gas exchanges occurs in ~0.25 which is 1/3 of time
required for transit through the lungs (.75 sec) at rest
and ½ this with exercise (transit time is .4 sec )
Exercise and Flow
• During exercise, pulmonary capillaries increase
blood volume X 3
• Maintain oxygenation during exercise
• PO2 arterial blood slightly lower than alveolar PO2
Gas Transfer in Tissues
• Rest
– PO2 in muscle tissue is 40 mm Hg
– Intracellular PCO2 av. 46 mm Hg
• Vigorous Exercise
– PO2 in muscle tissue falls toward 0 mm Hg
– Intracellular PCO2 av. 90 mm Hg
– Pressure differences between plasma and tissues
facilitate oxygen delivery and carbon dioxide removal
– Some blood in alveolar capillaries passes through
poorly ventilated alveoli
– Blood leaving the lungs joins venous blood from the
bronchial and cardiac circulations
•
Note
• Each liter of blood leaving the lungs
contains about 50 mL of carbon dioxide
– Provides the background level of carbon
dioxide that is the chemical basis for ventilatory
control through its stimulating effect on
neurons of the pons and medullary centers of
the brainstem
Transport of Oxygen
• Low solubility – 3 mL/L
• Sustain life for ~ 4 sec
• If dissolved oxygen provided the sole
source of oxygen, need a Q of 80 L/min to
supply resting metabolism (2X maximal
exercise)
• ???????????????????????????????????????
8
Enters: Hemoglobin
• Hemoglobin of RBC’s
– Iron containing protein pigment
– 280 million hemoglobin molecules in each of
body’s more than 25 trillion RBC's
– Carries 65-70 X more oxygen than dissolved in
plasma
– Temporarily captures and transports ~197 ml
oxygen/L blood
Oxygen Carrying Capacity
• Men - 15 g Hb/dL
• Women – 14 g Hb/dL
• Hemoglobin carries nearly 20 mL of
oxygen/dL of blood
Hemoglobin
• Hb4 + 4 O2
Hb4O8
• Each of 4 Fe atoms in hemoglobin can
loosely bind one oxygen
• No enzymes
• Partial pressure of oxygen dissolved in
dictates the oxygenation of hemoglobin to
oxyhemoglobin
Oxyhemoglobin Dissociation
Curve
• Oxygen saturation of Hb is %age of
available binding sites that have oxygen
attached
– O2 combined with Hb/ O2 capacity X 100
– Arterial blood 97.5% of Hb saturated with
oxygen (100 mm Hg)
– Mixed venous blood – 75% saturation (40 mm
Hg)
Oxyhemoglobin Dissociation
Curve
• Depicts the oxygen % hemoglobin
saturation and absolute oxygen
concentration of blood for a given PO2
– High PO2 almost complete saturation = 20
ml/dL
• PO2 of 100 mm Hg – Hb leaving lungs carries ~19.7
mL of oxygen/dL
• Plasma contains 0.3 mL/dL in solution
9
Oxyhemoglobin Dissociation
Curve
Oxyhemoglobin Dissociation
Curve
• Hemoglobin saturation changes little until
pressure of oxygen declines ~ 60 mm Hg
• Steep lower portion of curve –peripheral
tissues can withdraw large amounts of
oxygen for only a small drop in capillary
PO2
• Rest: PO2 in tissue = 40 mm Hg
– Flat upper part of curve provides a margin of
safety when have fluctuations in ambient PO2
• If alveolar PO2 drops to 75 mm Hg
– Hb saturation decreases by only 6%
– Hemoglobin loses about 30% of its oxygen
• 20 ml to 15 ml/100 mL
• Tissue utilized 5 ml/100 mL (a-v O2dif)
Oxyhemoglobin Dissociation
Curve
• Exercise – oxygen utilization increases
– Tissue PO2 decreases
• 15 mm Hg
• a-v O2dif = 15 ml/100 mL
• Hb releases more oxygen
Oxyhemoglobin Dissociation
Curve
• Decrease in pH – curve shifts downward and
to right – Bohr Effect
–
–
–
–
–
Altered Hb structure (20-50 mm Hg)
Oxygen affinity of Hb is decreased
For a given PO2, more oxygen unloaded in tissue
Increased a-v O2dif
Primarily related to effect of increasing PCO2 on
H+ concentration
Oxyhemoglobin Dissociation
Curve
• Curve shifts downward and to right
– Low pH (acidic)
– Hypercarbic
– Hot
“Conditions associated with exercise”
– 2,3-diphosphoglycerate (2,3 DPG) – produced by
RBC’s and binds Hb, decreasing its affinity for oxygen
– compensatory mechanism
• Cardiopulmonary disease
• High altitude
10
Altitude
• Barometric pressure decreases
exponentially with distance above the
earth’s surface
– 19,000 ft - ½ normal 760 mm Hg (380 mm Hg)
– PO2 = 70 mm Hg
– Summit of Mt Everest (29,029 ft) inspired PO2
= 43 m Hg
Myoglobin vs Hemoglobin
• Myoglobin found in skeletal and cardiac muscle
fibers
• Intramuscular storage of oxygen
• Each myoglobin molecule contains one Fe atom
• Facilitates the transfer of oxygen to mitochondria
when exercise begins and during intense exercise
when cellular PO2 declines rapidly
• Myoglobin dissociation curve – rectangular
hyperbola
– Low end of PO2 values – high saturation of myoglobin
with small increase in PO2
Acclimatization
• Hyperventilation
– Reduces PCO2 raising alveolar PO2
• Residents at 15,000 ft - PCO2 = 33 mm Hg vs 40 m Hg at sealevel
• Hypoxic stimulation of the peripheral chemoreceptors
• Polycythemia – increased RBC concentration of
blood
• Residents at 15,000 ft – arterial PO2 = 45 mm Hg but
arterial oxygen saturation is only 81% due to increased Hg (15
to 19.8 gm/100mL)
• Hypoxemia – causes release of erythropoietin from kidney
which stimulates bone marrow
Myoglobin
• PO2 = 40 mm Hg, myoglobin holds 95% of
its oxygen (rest and light exercise)
• As PO2 drops, the greatest quantity of
oxygen is released from myoglobin
• Myoglobin is not affected by pH,
temperature or carbon dioxide
11
Carbon Dioxide Transport
• 3 forms
– Dissolved
– Bicarbonate (HCO3- )
– In combination with proteins as carbamino
compounds
Dissolved Carbon Dioxide
• ~ 5-10% of arterial carbon dioxide moves
into solution
• Establishes the PCO2 of blood
Bicarbonate (70-75%)
• Tissue… Carbonic Anhydrase
• CO2 + H2O
H2CO3
H+ + HCO3• Reaction facilitated by carbonic anhydrase –
enzyme in RBC – 5,000 faster
• When HCO3- concentration rises in RBC, it
diffuses out
• To maintain chemical neutrality, Cl- ions
move into RBC (chloride shift)
Bicarbonate
• Some of H+ ions liberated are bound to Hb
– Triggers the Bohr Effect – formation of HCO3enhances oxygen unloading
– Hb acts as a buffer, preventing significant
increases in acidity
• Lungs where PCO2 is low – reaction reverses
O2 + HHb
HbO2 + H+
+
H + HCO3
H2CO3 CO2 + H2O
12
Carbamino Compounds (20%)
• CO2 combines with terminal amine group in
blood proteins
• Most important protein is globin of
hemoglobin
HbNH2 + CO2
HBNHCOOH
– Occurs rapidly without an enzyme
• When reach lungs plasma PCO2 decreases and
oxygenation of Hb reduces its ability to bind
carbon dioxide
Pulmonary Functions
Factors Affecting Performance
on Pulmonary Tests
• Motivation given to subject
• Position – standing optimal
• Illness – cold, allergy, etc.
Tests
• Static lung functions – volumes
• Dynamic lung functions – volume and
velocity
13
Determinants of Lung Functions
(prediction)
•
•
•
•
Race
Age
Gender
Height
Dynamic Functions
• Maximal Voluntary Ventilation (MVV)
– Volume of air that could be moved during
vigorous, deep breathing (extrapolated to a
minute)
– Test of ventilatory capacity
– 140-180 L/min (men)
– 80 – 120 L/min (women)
– Training of ventilatory muscles increases MVV
Dynamic Tests
• Velocity dependent on
– Airway resistance
– Resistance of lung tissue to change in shape
Dynamic Functions
• Single forced expiration
– FVC – total volume exhaled
– FEV1.0 – volume exhaled in first second
– FEV1.0/FVC – Forced expiratory ratio (FER)
• %
– Peak expiratory flow rate (PEFR) – highest
forced expiratory flow
• L/min
– FEF25-75% - Forced expiratory flow rate
• Average flow rate measured over the middle half of
the expiration (related to FEV1.0 )
Types of Pulmonary Disorders
• Restrictive – low lung volumes
•
•
•
•
•
Pulmonary fibrosis
Kyphoscoliosis
FVC < 80% of predicted
FEV1.0/FVC > 70% (normal for lower lung volume)
Inspiration limited by reduced compliance or weak
inspiratory muscles
Types of Pulmonary Disorders
• Obstructive - low flow rates
–
–
–
–
Asthma
Bronchitis
Emphysema
FEV1.0/FVC < 70%
14
Pulmonary Screening
•
•
•
•
Check for signs of restrictive disease:
Msd FVC/Pred FVC < 80%
Predict FVC – equation – Chp 4
Example
– 30 yr old, female, 64 inches, FVC = 3.20, FEV1.0 = 2.5
L
Pulmonary Screening
• Check for signs of obstructive disease:
– msd FEV1.0/ msd FVC < 70%
– 2.5/3.2 = .78 X 100 = 78%
– Normal
• Ok, so recheck in ……. years
FVC = (0.0414 X ht (cm) – (0.0232 X 30) – 2.2
FVC = (0.0414 X 162.6) – (0.0232 X 30) – 2.2
Predicted FVC = 3.83 L
3.2/3.83 = .84 X 100 = 84% - normal
Example
•
•
•
•
Asian male, age 35 years, 63 in. tall
FVC = 2.1 L
FEV1.0 = 1.33 L
Restrictive disease:
– Predicted = 3.89 X 0.85 = 3.31 L
– 2.14/3.31 = 64% (refer < 80%)
• Obstructive disease:
– 1.33/2.1 = 62% (refer < 70%)
Flow Volume Loops
• Subject inspires to total lung capacity and
then exhales as hard as he can to residual
volume
• Flow rate is independent of effort over most
of the lung volume
– High volumes – expiratory flow rate increases
with effort but at med and low volumes, flow
rate plateaus
– WHY??????
• Compression of airways by intrathoracic pressure
15
Asthma
• Reversible, bronchospasm triggered by
allergy, exercise, infections or
environmental irritants
– EIA (Exercise Induced Asthma) – epithelial
water loss and cooling of airways
– S/S - Increased secretion of nasal mucous, dry,
nonproductive cough, wheezing, SOB
Bronchitis
• Inflammatory disorder of small airways in
lung
• Common in smokers
• Productive cough, wheezing, reduced
arterial O2 saturation and increased CO2 due
to hypoventilation
EIA
• Most problematic – cold, dry environments
• 1984 Olympics Games in LA
– 11% US team – chronic EIA
– Won 41 medals
Emphysema
• Gradual destruction of lung alveolar cell units and
connective tissue and airway inflammation
• Enlargement of alveoli
• Loss of supporting tissue
• Airway collapse during expiration
• Total lung volume increases
• Dyspnea on exertion
• Limited functional capacity
• Arterial Desaturation
16
Static Lung Volumes
Respiratory Center
• Brainstem (medulla and pons)
• Establishes rate and depth of breathing
• Input from chemoreceptors, receptor
stretching in lungs
Oxygen Cost
Ventilation during Exercise
• Rest – 1-2% of total body oxygen consumption
• Heavy exercise - > 15% of total body oxygen
consumption
• Pulmonary ventilation not a limiting factor in
maximal performance unless restrictive or
obstructive lung disease
• Respiratory muscles better designed for avoiding
fatigue during long-term activity than muscles of
extremities
17
Ventilation During Exercise
• Ventilation - two-phase increase
• Immediate increase followed by a continued
gradual rise
– Initial – produced by mechanics of the body’s
movements
Entrainment
• A synchronization of limb movement and
breathing frequency
• Those who exhibit his have a lower energy
cost during exercise automatically
• Motor cortex transmitting impulses to respiratory
center
• Proprioceptive feedback from muscles to respiratory
center
Ventilation During Exercise
– More gradual increase in second phase
• Produced by changes in the temperature and
chemical status of the arterial blood
– H+, carbon dioxide, heat enhance unloading in muscles
– Increases arterial-venous dif
– More carbon dioxide enters blood
• Stimulates chemoreceptors which stimulate the
inspiratory center increasing rate and depth of
breathing
Ventilation Post Exercise
• Energy demand drop immediately
• Pulmonary ventilation returns to normal at a
slow rate
– Due to acid-base balance
– Carbon dioxide
– Temperature
18