RESPIRATORY PHYSIOLOGY

OBJECTIVES
Explain how the intrapulmonary and
intrapleural pressures vary during
ventilation and relate these pressure
changes to Boyle’s law.
Define the terms compliance and
elasticity, and explain now these lung
properties affect ventilation.
Discuss the significance of surface tension
in lung mechanics, explain how the law of
Laplace applies to lung function and
describe the role of pulmonary surfactant.
 OBJECTIVES
Describe the events that cause
inhalation and exhalation
Describe the roles of the medulla,
pons, and cerebral cortex in the
regulation of breathing.
 RESPIRATION
Includes 3 separate functions:
– Ventilation:
Breathing.
– Gas exchange:
Between air and capillaries in the lungs.
Between systemic capillaries and tissues of
the body.
Gas transport
– 02 utilization:
Cellular respiration.
 I- VENTILATION
 Mechanical process that moves air in and
out of the lungs.
 [O2] of air is higher in the lungs than in the
blood, O2 diffuses from air to the blood.
 C02 moves from the blood to the air by
diffusing down its concentration gradient.
 Gas exchange occurs entirely by diffusion.
 ALVEOLI
 ~ 300 million air sacs
(alveoli).
– Large surface area (60–
80 m2).
– Each alveolus is 1 cell
layer thick.
 2 types of cells:
– Alveolar type I
(squamous epithelial
cells) : Structural cells.
– Alveolar type II (septal
cells):
 Secrete surfactant.

Structural components of an alveolus

 CONDUCTING ZONE
All the structures air
passes through before
reaching the respiratory
zone.
Warms and humidifies
inspired air.
Filters and cleans:
– Mucus secreted to
trap particles in the
inspired air.
– Mucus moved by
cilia to be
expectorated.
 RESPIRATORY ZONE
 Region of gas exchange between air and blood.
 Includes respiratory bronchioles and alveolar
sacs.
 Must contain alveoli.
PHYSICAL PROPERTIES OF THE LUNGS
 Compliance:
– Distensibility (stretchability):
Ease with which the lungs can expand.
– 100 x more distensible than a balloon.
Compliance is reduced by factors that produce
resistance to distension.
 Elasticity:
– Tendency to return to initial size after distension.
– High content of elastin proteins.
Very elastic and resist distension.
– Recoil ability.
 AIRWAY RESISTANCE
The rate of airflow through the airways
depend on both the pressure difference and
the resistance
Larger diameter airways have decreased
resistance
Airway diameter is regulated by the degree
of contraction or relaxation of smooth
muscle on the walls of the airways
 SURFACE TENSION
 Force exerted by fluid in
alveoli to resist distension.
 Lungs secrete and
absorb fluid, leaving a
very thin film of fluid.
– This film of fluid causes
surface tension.
 H20 molecules at the surface
are attracted to other H20
molecules by attractive
forces.
– Force is directed inward,
raising pressure in alveoli.
 LAW OF LAPLACE

Pressure in alveoli is
directly proportional
to surface tension;
and inversely
proportional to radius
of alveoli.
– Pressure in smaller
alveolus greater.
 SURFACTANT
Phospholipid produced by
alveolar type II cells.
Lowers surface tension.
– Reduces attractive
forces of hydrogen
bonding by becoming
interspersed between
H20 molecules.
As alveoli radius
decreases, surfactant’s
ability to lower surface
tension increases.
 BOYLE’S LAW
Changes in intrapulmonary pressure occur
as a result of changes in lung volume.
– Pressure of gas is inversely proportional to its
volume.
Increase in lung volume decreases
intrapulmonary pressure.
– Air goes in.
Decrease in lung volume, raises
intrapulmonary pressure above atmosphere.
– Air goes out.
 LUNG PRESSURE
Intrapulmonary pressure:
– Intra-alveolar pressure (pressure in the alveoli).
Intrapleural pressure:
– Pressure in the intrapleural space.
– Pressure is negative, due to lack of air in the
intrapleural space.
Transpulmonary pressure:
– Pressure difference across the wall of the lung.
– Intrapulmonary pressure – intrapleural pressure.
 Keeps the lungs against the chest wall.
 QUIET INSPIRATION
Active process:
– Contraction of diaphragm, increases thoracic
volume vertically (responsible for 75% of the
air that enters the lungs) .
– Contraction of parasternal and internal
intercostals, increases thoracic volume
laterally.
– Increase in lung volume decreases pressure in
alveoli, and air rushes in.
Pressure changes:
– Alveolar changes from 0 to –3 mm Hg.
– Intrapleural changes from –4 to –6 mm Hg.
– Transpulmonary pressure = +3 mm Hg.
VENTILATION
 EXPIRATION
 Quiet expiration is a passive process.
– After being stretched, lungs recoil.
– Decrease in lung volume raises the pressure
within alveoli above atmosphere, and pushes
air out.
 Pressure changes:
– Intrapulmonary pressure changes from –3 to
+3 mm Hg.
– Intrapleural pressure changes from –6 to –3
mm Hg.
– Transpulmonary pressure = +6 mm Hg.
PULMONARY VENTILATION
 PULMONARY FUNCTION TESTS
Assessed by
spirometry.
Subject breathes into a
closed system in which
air is trapped within a
bell floating in H20.
The bell moves up
when the subject
exhales and down
when the subject
inhales.
LUNG VOLUMES
 SPIROMETRY
Spirometry is a
powerful tool
that can be
used to detect,
follow, and
manage
patients with
lung disorders.
SPIROMETRY

Spirometer
PFT
 LUNG VOLUMES
 Tidal volume : the amount of air
involved in one normal inhalation
and exhalation (500mL)
 Minute respiratory volume (MRV) :
the amount of air inhaled and
exhaled in 1 minute ( 500 x 12/min =
6000mL / min)
 LUNG VOLUMES
 Inspiratory reserve : the amount of
air, beyond tidal volume, that can be
taken in with the deepest possible
inhalation (2000mL -3000mL)
 Expiratory reserve : the amount of
air, beyond tidal volume, that can be
expelled with the most forceful
exhalation (1000mL-1500mL)
 LUNG VOLUMES
 Vitalcapacity : the sum of tidal
volume, inspiratory reserve, and
expiratory reserve (3000mL –
5000mL)
 Residual air : the amount of air that
remains in the lungs after the most
forceful exhalation (1000 mL-
1500mL)
Forced expiratory volume in
1 second (FEV1)
FEV1 is the volume of air that can forcibly be
blown out in one second, after full inspiration.
Average values for FEV1 in healthy people
depend mainly on sex and age, according to
the diagram at left.
Values of between 80% and 120% of the
average value are considered normal.
Predicted normal values for FEV1 depend on
age, sex, height, mass and ethnicity as well
as the research study that they are based on.
 FEV1/FVC RATIO
 FEV1/FVC (FEV1%) is the ratio of FEV1 to FVC. In healthy
adults this should be approximately 70–85% (declining
with age).[12]
 In obstructive diseases (asthma, COPD, chronic
bronchitis, emphysema) FEV1 is diminished because of
increased airway resistance to expiratory flow; the FVC
may be decreased as well, due to the premature closure
of airway in expiration, just not in the same proportion as
FEV1 (for instance
 In restrictive diseases (such as pulmonary fibrosis) the
FEV1 and FVC are both reduced proportionally and the
value may be normal or even increased as a result of
decreased lung compliance.
 FEV1/FVC RATIO
 A derived value of FEV1% is FEV1%
predicted, which is defined as FEV1% of
the patient divided by the average FEV1%
in the population for any person of similar
age, sex and body composition.
 LUNG VOLUMES
 FEV6 —Forced expiratory volume in six
6
seconds.
 FEF25–75%—Forced expiratory flow over
the middle one half of the FVC; the
average flow from the point at which
25 percent of the FVC has been
exhaled to the point at which 75
percent of the FVC has been exhaled.
 MVV—Maximal voluntary ventilation.
 PULMONARY FUNCTION TESTS

Most spirometers display the following graphs, called spirograms:

a volume-time curve, showing volume (litres) along the Y-axis and time
(seconds) along the X-axis
a flow-volume loop, which graphically depicts the rate of airflow on the Y-
axis and the total volume inspired or expired on the X-axis
 FLOW-VOLUME
LOOP
Flow-Volume loop showing
successful FVC maneuver.
Positive values represent
expiration, negative values
represent inspiration.
At the start of the test both
flow and volume are equal to
zero (representing the
volume in the spirometer
rather than the lung). The
trace moves clockwise for
expiration followed by
inspiration. After the starting
point the curve rapidly
 FVC
Forced vital capacity (FVC)
Forced vital capacity (FVC) is the
volume of air that can forcibly be
blown out after full inspiration,[10]
measured in liters. FVC is the most
basic maneuver in spirometry tests.
PULMONARY FUNCTION TESTS
 Normal spirometric
flow diagram. (A)
Flow-volume curve.
(B) Volume-time
curve. The smooth
lines, expiratory time
of greater than six
seconds, and quick
peak of the peak
expiratory flow rate
indicate a good
spirometric effort
Spirograms and flow
volume curves.
(A)Restrictive ventilatory
defect.
– Vital capacity is
reduced.
– FVC is normal.
(B) Normal spirogram.
(C) Obstructive
ventilatory defect.
– VC is normal.
– FEV1 is < 80%.
PULMONARY FUNCTION TESTS

LUNG CAPACITIES
FRC—Functional residual capacity; the volume of
air in the lungs at resting end-expiration.
 IC—Inspiratory capacity; the maximal volume of air
that can be inhaled from the resting expiratory
level.
 TLC—Total lung capacity; the volume of air in the
lungs at maximal inflation.
 VC—Vital capacity; the largest volume measured on
complete exhalation after full inspiration.
 Forced vital capacity (FVC) is the volume of air that
can forcibly be blown out after full inspiration,
measured in liters.
Normal Values of Pulmonary Function Tests
Normal value (95 percent confidence interval)
Pulmonary function test 80% to 120%
FVC 80% to 120% of the predicted value
Absolute FEV1 /FVC ratio : Within 5% of the
predicted ratio
TLC 80% to 120%
FRC 75% to 120%
RV 75% to 120%
 Parameters % Pred

(S)VC(L) Slow Vital Capacity > 80%

FVC(L) Forced Vital Capacity > 80%
FEV1(L) Forced Expiratory > 80%
Volume during 1st
second
FEV1/VC Tiffeneau > 70%
FEV1/FVC Gaensler > 70%
FEF25-75% Forced Expiratory Flow > 60%
during the middle half
of FVC
PEF(L/S) Peak Expiratory Flow > 80%
MVV(L/M) Maximal Voluntary > 60%
Ventilation
 ANATOMICAL DEAD SPACE
Not all of the inspired air reached the
alveoli.
As fresh air is inhaled it is mixed with air in
anatomical dead space.
– Conducting zone and alveoli where [02] is
lower than normal and [C02] is higher than
normal.
Alveolar ventilation = F x (TV- DS).
– F = frequency (breaths/min.).
– TV = tidal volume.
– DS = dead space.
 PHYSIOLOGICAL DEAD
SPACE
 Physiologicdead space : the volume
of non-functioning alveoli that
decrease gas exchange
 PULMONARY DISORDERS
 Dyspnea:
– Shortness of breath.
 COPD (chronic obstructive pulmonary
disease):
– Asthma:
 Obstructive air flow through bronchioles.
– Caused by inflammation and mucus secretion.
 Inflammation contributes to increased airway
responsiveness to agents that promote bronchial
constriction.
 IgE, exercise.
 PULMONARY DISORDERS
Emphysema:
 Alveolar tissue is destroyed.
 Chronic progressive condition
that reduces surface area for
gas exchange.
– Decreases ability of
bronchioles to remain open
during expiration.
– Cigarette smoking
stimulates macrophages
and leukocytes to secrete
protein digesting enzymes
that destroy tissue.
 PULMONARY DISORDERS
Pulmonary fibrosis:
– Normal structure
of lungs
disrupted by
accumulation of
fibrous
connective tissue
proteins.
 Anthracosis.
 II- GAS EXCHANGE IN THE LUNGS
 Partial pressure:
– The pressure that an
particular gas exerts
independently.
 P
ATM = PN2 + P02 + PC02 +
PH20= 760 mm Hg.
– 02 is humidified = 105 mm
Hg.
 H20 contributes to partial
pressure (47 mm Hg).
– P02 (sea level) = 150
mm Hg.
– PC02 = 40 mm Hg.
 SIGNIFICANT OF PO2 AND PCO2
MEASUREMENTS
At normal P02
arterial blood = 100
mm Hg.
P02 level in the
systemic veins is =
40 mm Hg; PC02 =
46 mm Hg.
Provides a good
index of lung
function.
 PULMONARY CIRCULATION
Rate of blood flow through the pulmonary circulation
is = flow rate through the systemic circulation.
– Driving pressure is about 10 mm Hg.
Pulmonary vascular resistance is low.
– Low pressure pathway produces less net filtration than
produced in the systemic capillaries.
Autoregulation:
– Pulmonary arterioles constrict when alveolar P0
2

decreases.
– Matches ventilation/perfusion ratio.
 LUNG VENTILATION/PERFUSION RATIOS

Functionally:
Alveoli at
apex are
underperfused
4 5 0.8
(overventilated).
Alveoli at the base
are underventilated
(overperfused).
 O2 TRANSPORT
 280 million hemoglobin/RBC.
 Each hemoglobin has 4
polypeptide chains and 4
hemes.
 In the center of each heme
group is 1 atom of iron that
can combine with 1 molecule
02--- oxyhemoglobin
 OXYHEMOGLOBIN
Methemoglobin:
Lacks electrons and
cannot bind with 02.
Blood normally
contains a small
amount.
Carboxyhemoglobin:
The bond with carbon
monoxide is 210 times
stronger than the bond
with oxygen.
Transport of 02 to
tissues is impaired.
 HEMOGLOBIN
 Oxygen-carrying capacity of blood
determined by its [hemoglobin].
– Anemia:
 [Hemoglobin] below normal.
– Polycythemia:
 [Hemoglobin] above normal.
– Hemoglobin production controlled by
erythropoietin (EPO).
 Production stimulated by P C0 delivery to kidneys.
2

 Loading/unloading depends:
– P0 of environment.
2

– Affinity between hemoglobin and 02.

 OXYHB DISSOCIATION CURVE
Graphic illustration of the %
oxyhemoglobin saturation at
different values of P02.
Loading and unloading of 02.

Steep portion of the sigmoidal

curve, small changes in P02
produce large differences in %
saturation (unload more 02).
Decreased pH, increased
temperature, and increased 2,3
DPG:
– Affinity of hemoglobin for 02
decreases.
– Greater unloading of 02:
– Shift to the curve to the
right.
 OXYHB DISSOCIATION CURVE
Effects of pH and
temperature
Affinity is
decreased when pH
is decreased.
Increased
temperature and
2,3-DPG:
– Shift the curve
to the right.
OXYHB DISSOCIATION CURVE

Effects of temperature and 2,3 DPG

OXYHB DISSOCIATION CURVE
 CO2 TRANSPORT
 C02 transported in the blood:
2

– HC03- (70%).
– Dissolved C02 (10%).
– Carbaminohemoglobin (20%).

Carbonic Anhydrase

H20 + C02 H2C03

High PC02
 CHLORIDE SHIFT AT SYSTEMIC
CAPILLARIES
H20 + C02 -- H2C03 -- H+ + HC03-
At the tissues, C02 diffuses into the RBC;
shifts the reaction to the right.
Increased [HC03-] produced in RBC:
HC03- diffuses into the blood.
RBC becomes more +.
Cl- attracted in (Cl- shift).
H+ released buffered by combining with
deoxyhemoglobin.
HbC02 formed.
Unloading of 02.
CHLORIDE SHIFT AT SYSTEMIC
CAPILLARIES

CO2 HCO3- CL-

H20 + C02 H2C03 H+ + HCO3-

Carbonic anhydrase
 AT PULMONARY ARTERIES

H20 + C02 H2C03 H+ + HC03-

At the alveoli, C02 diffuses into the alveoli;
reaction shifts to the left.
Decreased [HC03-] in RBC, HC03- diffuses into
the RBC.
– RBC becomes more -.
 Cl- diffuses out (reverse Cl- shift).
Deoxyhemoglobin converted to
oxyhemoglobin.
– Has weak affinity for H+.
Gives off HbC02.
 VENTILATION DURING EXERCISE
During exercise, breathing
becomes deeper and more rapid.
Produce > total minute volume.
Neurogenic mechanism:
– Sensory nerve activity from
exercising muscles
stimulates the respiratory
muscles.
– Cerebral cortex input may
stimulate brain stem
centers.
Humoral mechanism:
– PC02 and pH may be
different at chemoreceptors.
– Cyclic variations in the
values that cannot be
detected by blood samples.

Figure 19–3
 LACTATE THRESHOLD AND
INDURANCE TRAINING
 Maximum rate of oxygen consumption that
can be obtained before blood lactic acid
levels rise as a result of anaerobic respiration.
– 50-70% maximum 02 uptake has been reached.
 Endurance trained athletes have higher
lactate threshold, because of higher cardiac
output.
– Have higher rate of oxygen delivery to muscles.
– Have increased content of mitochondria in skeletal
muscles.
 ACCLIMATIZATION AT HIGH ALTITUDE
Adjustments in respiratory function when
moving to an area with higher altitude:
Changes in ventilation:
– Hypoxic ventilatory response produces
hyperventilation.
 Increases total minute volume.
 Increased tidal volume.

Affinity of hemoglobin for 02:

– Action of 2,3-DPG decreases affinity of hemoglobin
for 02.
Increased hemoglobin production:
– Kidneys secrete erythropoietin.
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