# MPHYS Exam 2 Notes (Respiratory)

```Mechanics
1. Volumes and capacities
a) Air volumes measured by spirometer, plus Residual Volume (RV), which
cannot be measured directly from air flow
(1) Total Lung Capacity (TLC) cannot be measured by spirometry
(2) Diffusing Capacity (DLCO) cannot be measured by spirometry
b) Lung volumes and capacities
(1) Tidal Volume (Vt): volume of gas (0.5L) inspired during quiet
breathing
(2) Functional Residual Capacity (FRC): volume of gas in the lungs at
the end of a passive expiration (2700 ml**). Represents the
equilibrium position achieved when respiratory muscles are
relaxed and the inward elastic recoil of the lungs is exactly
balanced by the outward elastic recoil of the thorax.
(a) FRC = ERV + RV (expiratory residual volume + residual
volume)
(b) The elastic properties of the lung will determine the FRC:
(i)
Elastic lungs (fibrosis): FRC is decreased and
patient appears sunken-chested. Lung is
‘non-compliant’
(ii)
Inelastic lungs (emphysema): FRC is increased.
Once you have lost elasticity in lungs, you cannot
get it back. Emphysemic patients are often
barrel-chested; lungs are very compliant. To
counter the forces of the chest wall, large volumes
of air are required.
(c) Determination of FRC cannot be done with spirometry;
instead, techniques such as He-dilution and N2-washout
can be used to find FRC, as well as TLC (b/c they can
measure RV)
(3) Inspiratory Capacity (IC): maximal volume of gas that can
be inspired from resting expiratory level (4000 ml)
(a) IC = IRV + V(t)
(4) Inspiratory Reserve Volume (IRV): additional volume of
gas that can be inspired beyond end-tidal inspiration
(5) Expiratory Reserve Volume (ERV): additional volume of
gas that can be expired from resting expiratory level (1500
ml)
(6) Residual Volume (RV): volume of gas in the lungs at
the end of a maximal expiration (1200 ml**)
(7) ​Vital Capacity (VC): maximal volume that can be expired
at the end of a maximal inspiration (5500 ml)
(a) VC = IRV + ERV + V(t)
(b) When done quickly and forcefully, it is “​Forced
Vital Capacity​​”, ​FVC
(c) Peak Expiratory Flow rate (PEF)​​ = Maximum flow
rate achieved during a forced vital capacity
(8) Total Lung Capacity (TLC): volume of gas in the lungs at
the end of a maximal inspiration (6700 ml**)
(9) Forced Expiratory Volume(1sec): [FEV(1sec)]: The volume
of air exhaled in the first second of a FVC maneuver
(a)
(b) Normal ratio of FEV(1sec) to FVC is ​80% (70-85%).
During a forced expiration, IPP becomes positive
and airways are compressed. Maximum expiratory
flow rates are “effort independent”, making them
better indicators of pulmonary function.
(c) Forced Expiratory Volume(25-75) - FEV(25-75):
the volume of air exhaled in the mid-portion of a
FVC maneuver, between the 25 and 75% of the VC
exhaled
c) Effort-Independent flow: Max airflow at 50% is independent of
effort, b/c the pressure gradient remains 8cm H2O
(1) Same gradient, but smaller flow rate would indicate greater
resistance
d) Flow-time and Flow-Volume
(1) Flow-time = FVC, FEV(1sec), FEF(25-75%)
(2) Flow(L/s)-Volume loop
(a) Generally look at expiration curve (​nearly all ​PFT is
done on expiratory volumes)
(b) Peak expiratory flow
(c) Developed from TLC to RV, measure FVC
(d) These tests require blowing out for 6 seconds - not
easy.
e) Subdivisions of Lung Capacities:
B. Pressures during a respiratory cycle
1. Air movement
a) Bulk flow through a tube
(1) Similar to Ohm’s law
(2) Predicts flow in a circuit due to pressure gradient and resistance
(3) , ሶ =
∆/R
(a) Q = flow in units of Volume per Unit Time
(b) ∆ is the pressure gradient across resistance R
b) Nature of airflow
(1) In the respiratory tree, molecules move by either bulk flow or
diffusion. ​Bulk flow ​depends on the pressure gradient, and the
resistance. Bulk flow may occur in
(a) Turbulent
(b) Laminar, or
(c) Transitional (a combination of the two) forms
(2) Diffusion is the result of random Brownian motion; diffusion
(a) O2 concentration gradients between points A and B
(b) CO2 concentration gradients between points A and B
(i)
Neural - controlled
(a) Parasympathetic -> bronchoconstriction
(b) Sympathetic -> bronchodilation
(ii)
Mechanical
(a) The more negative IPP associated with
larger lung volumes widens
The ​medium-sized bronchi ​are the major site of
airway resistance.
(a) The smallest airways would seem to offer
the highest resistance, but they do not
because of their parallel arrangement
(d) Vascular resistance - recruitment & distension
(i)
Adding vessels in parallel and vasodilation of
perfused capillaries are the two ways that the body
can reliably increase blood flow. Both lower total
pulmonary circulation resistance allowing increased
blood flow to the pulmonary circulation with little
(ii)
Alveolar & extra-alveolar vessels
(iii)
(a) at low lung volume, low pressure, the
alveolar vessels are biggest
(b) at high lung volume, high thoracic pressure,
the extra-alveolar vessels are bigger while
the alveolar vessels are smallest
(c) Thus, both when lung approaches Residual
Volume AND when it approaches Total Lung
Capacity, pulmonary vascular resistance
goes up
c) Gravitation effects on flow
(1) At Zone 1 (above the level of the heart), PA (alveolar) is greater
than Pa (arterial); the alveolar pressure then occludes the artery a
bit. Exercise then increases PA enough to overcome this Pa.
(2) At Zone 2 (at the level of the heart), F(G) becomes smaller: Pa >
PA > Pv essentially all of the time, so there is a higher relative flow
(3) At Zone 3 (below the level of the heart), F(G) contributes to the
pressure, so Pa > Pv > PA. Blood flow is greatest near the base of
the lung, then, within Zone 3
(4) When you lay down, these gravitational effects are abolished.
Blood flow at the apex and base of the lung will be essentially the
same!
d) Bulk flow
(1) Turbulent flow - causes vibrations/sounds an MD can hear with a
stethoscope
(a) Large airways (trachea and main bronchi)
(b) Pressure gradient responsible for flow is related to the square of
the pressure: doubling flow requires fourfold increase in pressure
(2) Laminar flow
(a) Small airways
(b) Flow is directly related to the pressure gradient (i.e. air flow obeys
ohm’s law)
e) Reynolds’ Number = (Velocity * Diameter * Density) / Viscosity
(1) Reynolds’ number < 2000 -> laminar flow
(2) Reynolds’ number > 2500 -> turbulent flow
(3) Between, it may be transitional
f) Alveolar ventilation
(1) Alveoli, like capillaries, are only 1 cell thick
(2) Two areas in the lungs
(a) gas exchange zones (or respiratory zones)
(b) dead space regions - no gas exchange occurs
(3) Ventilation is the tidal air - air in the dead space: V(A) = V(T)-V(D)
(4) Alveolar ventilation per minute: V(A) = (V(T) - V(D))*f (f = frequency of
breathing)
g) Ventilation
(1) in normal conditions, alveolar dead space is thought to be essentially
(a) if alveoli have collapsed, or for some reason air cannot get out of
an alveolus, then it has become dead space
(b) likewise, an embolus (blood clot) in alveolar vessel also gives rise
(2) A good way to estimate a normal dead space is to take ideal body weight
(lbs) and make it ml; so 150lb person should have 150ml of ​anatomical
(a)
h) Respiratory Pattern - Slow, deep breathing
i)
f
VT
F*VT
=ሶ
VT-VD
=Valv
F*Valv
=ሶ alv
15
500
7500
350
5250
7.5
1000
7500
850
6375
30
250
7500
100
3000
Air movement into the lungs
(1) Air flows from a region of high pressure to a region of low pressure.
(2) Contraction of the respiratory muscles during inspiration enlarges the
thoracic cavity.
(a) Unforced Inspiration
(i)
Diaphragm
(ii)
External Intercostals
(b) Forceful Inspiration
(i)
Diaphragm
(ii)
External Intercostals
(iii)
Sternocleidomastoid
(iv)
Scalenes
(3) The lungs are in close apposition to the respiratory muscles, separated
from them by the pleural "space", which contains no gas and only a small
volume of fluid (<15 ml).
j)
(4)
Respiratory Cycle
(1) in a sealed environment, the product of pressure and volume are
constant
(2) During inspiration, there is a pressure gradient from outside air, into the
lungs. At the end of inspiration, the pressure gradient is gone
(3) During expiration, the elasticity of the lungs raises the intraalveolar
pressure by 2mmHg, the same amount by which intraalveolar pressure
was lowered during inspiration. This drives expiration
k) Sequence of events in a normal respiratory cycle
(1) Inspiratory muscles (diaphragm, external intercostals) contract
(2) Thorax enlarges
(3) IPP​​ (intrapleural pressure) becomes more negative
(4) Lungs enlarge
(5) IAP​​ becomes negative
(6) Air moves into the lungs
(7) Expiration depends on the elastic recoil of the lungs
l) Alveolar pressure during respiratory cycle
(1) The ​transmural pressure ​is responsible for lung
movement; calculated as the difference between IAP and
IPP (IAP-IPP)
(2) The fluid in the intrapleural space is subjected to a
“distending” force, and its pressure is negative
(subatmospheric)
(3) If you force expiration, you get initial increase in the peak
airflow. However, airflow becomes independent of
pressure after a certain point; when the pressure drop falls
below 30, the bronchioles and terminal bronchioles
collapse in the soft areas. When that happens, you get
zero airflow
(4) 8cm is the actual gradient for airflow; exceeding that level
has no impact on airflow rate
(5)
m) Regional variation in IPP: ​Due to gravity, IPP varies with the
position of the thorax. The most dramatic variation is from apex
to base, when the thorax is in the erect position.
n) Normal IPP
(1) IPP fluctuates solely in negative range during normal
respiratory cycle. But it can become positive under certain
circumstances
(a) Inspiration: ​during positive pressure respiration,
the outward movement in the lungs “compresses”
the intrapleural space and raises its pressure
(b) Expiration: ​during an active expiration, the
respiratory muscles “compress” the intrapleural
space, i.e. IPP becomes positive, so that lungs
and more forcefully
o) Pneumothorax
(1) Perforation in the chest wall or lung causes air to move
into the intrapleural space, because IPP is negative. Air in
the IPS breaks the seal that attaches lung to chest wall,
and that region of the lung collapses (IPP equalizes to
atmospheric pressure). The chest wall expands at the
same time
(2) Under normal conditions, the lungs pull the chest wall
inward
p) Traumatic pneumothorax
(1) Chest wound causes air to move from environment into
the IPS
(2) Rupture of an alveolus by barotrauma causes air to move
from IAS into IPS, e.g. inflation pressure > 50cm H2O
during positive pressure respiration, or volume trauma
(diver failing to exhale during rapid ascent)
q) Spontaneous Pneumothorax
(1) Spontaneous rupture of an alveolus causes air to move
from IAS into IPS. Occurs most commonly at the apex
where the more negative IPP is suspected of imposing
large stress on the alveolar wall
(a) The flaps of the ruptured wall usually reseal and
limit the volume of air that accumulates
(b) If air continues to accumulate, lungs will
completely collapse and seriously compromise
both gas exchange and cardiac mechanics.
“​Tension pneumothorax”
r) Positive Pressure Respiration​​ - Mechanical Breathing
(1) Atmospheric pressure is raised as it is pumped into a
patient. Airways tend to narrow and there are negative
consequences because it’s not ‘real’ breathing
(2) Gases that are expired are expired to a peak pressure,
such that the lungs are always kept expanded! Only works
when Trachea is kept sealed off and cannulated - so for
patients that are unconscious
(3) Assisted Control Mode Ventilation​​ (ACMV): Inspiratory
cycle initiated by patient or automatically if no signal
detected within a specified time window.
(4) Positive End Expiratory Pressure ​(PEEP): By not allowing
IAP to return to O cm H2O at the end of expiration, the
lung will be kept at a larger volume.
(5)
s) Positive Pressure Respiration - ​Spontaneous
(1) Continuous Positive Airway Pressure (CPAP):​​ not a true
support-mode of ventilation. Breathing is spontaneous
but via a circuit that is pressurized. CPAP used to maintain
airway size and prevent respiratory muscle atrophy. It is
the primary treatment for Obstructive Sleep Apnea
(“pneumatic stent”).
(a) face mask pressurizes air to +5cmH2O; the patient
breathes spontaneously
(i) patient starts at higher pressure, lowers the
IAP, and inspiration/expiration proceeds as
normal
(ii) By putting constant pressure, it helps
prevent airway collapse as seen in OSA
(obstructive sleep apnea)
t) Obstructive Sleep Apnea:
(1) Typically occurs in obese patients, where adipose tissue /
larger mouth is attached to surrounding connective tissues
and skeletal muscle.
(2) Skeletal muscle is more relaxed when asleep than when
awake. By raising pressure surrounding the nasal cavities,
an artificially higher pressure is generated in the airways,
effectively treating sleep apnea
u) Lung compliance on ventilation
(1) Because of gravity-driven variations in IPP, the alveoli at
the apex are partially distended long before the alveoli at
the base have begun to inflate.
(2) At apex, volume starts high but changes little. At base,
volume starts low but changes a lot - so there is greater
ventilation at the base of an upright lung, due to gravity.
When an individual is lying down, the effect is nearly
abolished. In other words, in the upright lung, there is
lower compliance ​at the ​apex.
2. Blood movement
a) ​The flow rate through pulmonary circulation is EQUAL to that of
systemic circulation. Therefore, since the pulmonary pressure is ⅙
that of systemic pressure, pulmonary resistance is also ⅙ that of
systemic circulatory resistance
(1)
b) Lung blood flow: pulmonary & bronchial arteries
(1) Pulmonary blood flow: blood flow that is delivered to the
alveoli. Cardiac output of the right ventricle (to pulmonary
circ.) is equal to that of the left ventricle (to systemic circ.)
(2) Bronchial arteries & veins supply nutrients to the tissues of
the lungs. ​very s​ mall fraction of total blood going to the
lungs, because it never comes into contact with the gas
exchange regions of the lung. It is shunted directly from the
left to the right sides of the lung (a “shunt flow”)
(3) Poiseuille’s law: Q = ∆P/(8ηl /R4)
(a) ΔP is the pressure gradient
(b) η is viscosity, which changes resistance to airflow.
During deep-sea diving, air density and resistance
to airflow are both increased. Breathing low-density
gas, such as Helium, reduces the resistance to
airflow.
(c) ℓ is length
(d) N is number of vessels in parallel
(e) R (radius of a vessel) is the biggest influence on
flow: doubling the radius corresponds to a 16-fold
increase in flow
(4) Blood flow in an erect lung
(a) Gravity affects blood flow also; blood flow is
considerably lower at the apex of an upright lung.
The effect is even greater than that of ventilation.
(i)
Arterioles/capillaries at the apex collapse
(ii)
Blood flow increases at the base of the
lungs
(b) Bottom line: ​both ventilation and blood flow are
lowest at the apex of an upright lung.
3. Restrictive lung disease
a) Obstructive Pulmonary Disease: characterized by increase in
airway resistance and measured as decrease in expiratory flow
rates. Airways tend to be partially collapsed, which affects flow
rate. Also affects volumes.
(1) Chronic bronchitis: hypertrophied smooth muscle and
mucus glands, increased mucus secretion -> narrow
airways
(2) Asthma: hyperreactive airways, inflammation (cellular
infiltrates, tissue edema) -> narrow airways
(3) Emphysema: loss of tissue elasticity -> loss of support for
small airways -> easily distorted airways. With loss of
tissue elasticity, airway collapse is common, trapping the
air that cannot get out - dead air is added to Residual
Volume. TLC may be slightly elevated because of
increased RV, but it remains pathological as RV does not
contribute to gas exchange.
(4) Spirometry in obstruction:
(a)
(b) Flow-Vol curves in Obstruction
(c)
(d) Peak flow less than normal in emphysema; bend in
expiratory flow is due to pinching of smaller
airways. Because flow rate is lower, it can take
patients much longer periods of time to exhale to
the same degree
(e) Don’t memorize these graphs, but be able to
interpret them. Flow rates are lower in cases of
obstruction
b) PFT in Bronchoconstriction - would show ​greater flow rates ​at
each point on the curve for a patient with asthma, after
c)
4. Lung Elasticity - Work
a) Elasticity is property of matter that causes it to resist distortion;
elastic tissue returns to original shape after having been
deformed. Measures of elasticity tell you how “stiff” a lung is; the
more elastic, the more work to get a set volume
b) Work of breathing (W) = Pressure (P) x Change in volume (ΔV)
(1) W = P*ΔV
(2) “Out of breath” feeling is when respiratory muscles are
unable to maintain normal elasticity
c) Lung compliance - elastance
(1)
(2) The P-V relationship for the normal lung shown describes
the fallin IPP required to obtain a change. The slope of the
curve is a measure of lung compliance; the inverse of
elasticity in lung volume
(3) The curve is nonlinear ​and becomes flat at high expanding
pressures
(4) Compliance: C = V/P (volume / pressure)
(a) Describes the ​distensibility ​of the lungs and chest
wall
(b) Is inversely related to ​elastance, ​which depends on
the amount of elastic tissue
(c) Is inversely related to stiffness
(d) Is the slope of the P-V curve (above). Pressure
refers to transmural, or transpulmonary, pressure
(alveolar pressure - intrapleural pressure)
(e) In the middle range of pressures, compliance is
greatest and the lungs are the most distensible.
(f) At high expanding pressures, compliance is lowest,
the lungs are the least distensible, and the curve
flattens.
d) Compliance in a diseased lung
(1)
e) Surfactant ​reduces surface tension and thus increases lung
compliance - greatly reducing the work of respiration. ​Without
surfactant, ​surface tension of the film lining the inside of the
alveolus is constant: P = 2ST/r, where ST is surface tension and r is
(1) Smaller radius = greater pressure
(2) Small alveoli would ‘inflate’ larger alveoli if connected;
collapsing into the larger alveoli.
(3) Surfactant adjusts the 2ST ratio such that Psmall = Plarge
(4) Is synthesized by ​Type II alveolar cells ​and consists
primarily of the phospholipid ​dipalmitoyl
phosphatidylcholine (DPPC)
f) Surfactant respiratory distress (RDS) ​of a newborn
(1) Lung washings from infants with Respiratory Distress
Syndrome of the Newborn (RDS) have a high surface
tension that shows little variation in S.T. with area.
(2) The lungs are very Elastic, difficult to inflate
(3) Premature birth and maternal diabetes are risk factors.
(a) A lecithin/sphingomyelin ratio (L/S) of 2.0 or
greater indicates lung maturity and a minimal risk
for RDS.
(b) A gestational age of 34 weeks divides those with
increased incidence and mortality from those
relatively free of the disorder.
(4) Interdependence: Alveoli share septa and do not exist as
independent units
5. Restrictive lung disease - characterized by an increase in elasticity that is
measured as a decrease in all lung volumes.
a)
(1) Examples of Restrictive lung diseases
(2) RDS of the newborn
(3) Fibrotic lung disease
(4) Pulmonary vascular congestion (congestive heart failure)
6. Flow-Volume loops in disease
a)
b) Restrictive diseases​​ show similar shapes of flow-volume loops,
but flow rates and volumes are smaller
c) Obstructive diseases​​ show aberrant shapes of F-V loops
7.
II.
Respiratory muscles
Gas Exchange
1. Bulk Airflow
a. As the number of branches increases in the lungs, resistance decreases
even though the radius of airways is decreasing. Why decreased
resistance? Poiseuile’s law! More vessels are being added in parallel per
branching; this overcomes the radius contribution to resistance
2. Gas exchange
a. Gas movement across alveolar-capillary wall occurs by passive diffusion.
c. The partial pressure of a gas reflects that part of the Total Barometric
Pressure (TBP) for which that gas is responsible.
3. Partial P of a Gas in Ambient Air: P = F(gas)*TBP
a. Example: Oxygen is 21% of air: PO2 = 0.21(760) = 159mmHg
4. Gas diffusion
a. V(gas) = AxDx(P1-P2)/T
i.
A = alveolar tissue area
ii.
D = alveolar diameter?
iii. P1-P2 = gradient between CO2 in the blood / out of the blood, plus
O2 in the blood / out of the blood
iv.
T = alveolar wall thickness
b. Under most conditions in a normal long, blood leaving in Pulmonary
Capillary has the same O2 and CO2 level as the air in the alveolus
i.
~750ms in capillary for a given molecule
ii.
O2 and CO2 are perfusion limited
iii. Under excercise conditions, capillary transit time decreases to
250ms
iv.
In abnormal lung function, it takes longer for gas to transit the
capillary, gas exchange is impaired. This may not show up except
when the system is stressed (i.e. by exercise)
c. Partial Pressure of a gas in “inspired” air (air inhaled, warmed to 37C and
totally saturated with water vapor, but has not yet engaged in gas
exchange)
i.
Partial pressure of H2O depends only on temperature, and at 37C
is 47mmHg
ii.
Partial pressure of alveolar gas depends on ratio of alveolar
ventilation (Va) to pulmonary capillary blood flow (Qc, or ‘perfusion’)
1. Ideal Va/Qc = 0.8
iii. Changes in Va/Qc
d. Low Va/Qc: ​hypoxic and hypercapnic
i.
Decreased PaO2, increased PaCO2
ii.
Obstruction in airway restricts ventilation
e. High Va/Qc:
i.
Increased PaO2, decreased PaCO2
ii.
Overventilation can occur when airways are normal, but blood flow
is occluded (pulmonary embolism!) so Oxygen levels can build up,
but little blood comes through.
f. Example:
5. CO2 gas equation
a. PaCO2 = (VCO2/Va)*k
i.
PaCO2 = partial pressure of CO2 in arterial blood
ii.
VCO2 = CO2 production / minute
iii. Va = alveolar ventilation / minute
iv.
K = 0.86, a constant
6. Ideal alveolar gas equation: ​PaO2 = PiO2 - (PaCO2/R) + F
a. PaO2 = partial pressure O2 in alveoli
b. PiO2 = partial pressure of inspired O2
c. PaCO2 = partial pressure of CO2 in the alveoli
d. R = respiratory exchange ratio (varies at rest from 0.7 to 1.0)
i.
7.
d.
e.
f.
g.
h.
R = VCO2/VO2 = mlCO2 exchanged across lung per minute / mlO2
exchanged across lung per minute
ii.
R = 1 for glucose
iii. R = 0.8 for typical at rest
iv.
R = 0.7 for fatty acid
e. F = correction, usually ignored, typically ~ 2 mmHg
Alveolar O2 levels
a. PaO2 = PiO2 - PaCO2/R
b. PaO2 = 0.21(760-47) - 40/0.8
i.
= 99mmHg
c. Breathing 100% O2, PaO2 = 1.0(760-47) - 40/0.8
i.
= 663 mmHg (maximum theoretical alveolar O2 level)
O2 Transport
i.
Dissolved
1. Linear with PO2 in the blood, & little effect on total O2
ii.
Bound to Hb
1. By far the greatest factor.. Near maximum, normally
iii. Concentration vs content
1. O2-Hb responsible for major part of content
2. Volume % (Vol %). = ml O2 per 100ml blood
O2 Transport
i.
At a PO2 of 100mmHg
1. 0.3ml O2 is dissolved in 100 ml blood (0.3 vol %)
2. PO2 to 130-135 with maximum hyperventilation (0.4 vol %)
O2 Transport - Oxyhemoglobin binding
i.
PO2 is 100 mmHg, Hb is 97.5% saturated with O2
ii.
PO2 is 40 mmHg, 75% of O2-binding sites on Hb are occupied
iii. % saturation is independent of the amount of Hb
HbO2 content
i.
Number of ml of O2 carried in each 100ml of Blood depends on [Hb] and
PO2
ii.
Each gram Hb can combine with 1.34ml O2
iii. [Hb] is 15gm/100ml blood
HbO2 content in blood: CaO2 = (1.34 x [Hb])*(% saturation HbO2)
i.
O2 content is dependent on the amount of hemoglobin. CaO2 directly
reflects the total number of oxygen molecules in arterial blood (both bound
and unbound to Hb)
ii.
Typical values are 16-22
iii.
i.
Shape of HbO2 dissociation curve is sigmoidal; hyperventilation can
increase PaO2, but does little for HbO2 content (~ 0.1% boost)
Causes of Hypoxia
i.
Hypoxia = decreased delivery of oxygen to the tissues.
1. O2 delivery = Cardiac Output x O2 content of blood.
2. Hypoxia can be caused by decreased Cardiac Output,
decreased O2-binding capacity of Hb, or decreased arterial
PO2 (hypoxemia)
3. In the lungs, hypoxia causes vasoconstriction. This is the
opposite of what is seen in other organs, where hypoxia
causes vasodilation. This is important physiologically b/c local
vasoconstriction redirects blood away from poorly ventilated,
hypoxic regions of the lung and towards well-ventilated
regions.
4. Fetal pulmonary vascular resistance is very high b/c of generalized
hypoxic vasoconstriction; as a result, blood flow through the fetal
lungs is low. With the 1st breath, alveoli of the neonate are
oxygenated, pulmonary vascular resistance decreases, and
pulmonary bloodflow increases and becomes equal to cardiac
output (as occurs in the adult)
Cause
Mechanisms
Decreased Cardiac Output
Decreased bloodflow
Hypoxemia
Decreased PAO2, causes decreased %
saturation of Hb
Anemia
Decreased Hb concentration causes
decreased O2 content of blood
CO poisoning
Decreased O2 content of blood
Cyanide poisoning
Decreased O2 utilization by tissues
j.
Causes of hypoxemia (​Hypoxemia - a decrease in arterial PO2)
i.
Va/Qc mismatch
1. Regional variation in Va/Qc (difference in ratio of ventilation
to flow at the apex, compared to the base. Under normal
conditions, there is a wide variation that ultimately produces
the normal pattern of gas exchange.
ii.
Cause
2. In Va/Qc mismatch, Va/Qc of diseased units is less than
ideal, but non-zero. It is responsible for the hypoxemia seen
in many pulmonary diseases
a. COPD, interstitial lung disease
3. Hyperventilation of healthy lung units ​does not ​add sig.
Quantities of O2 to blood
a. Va/Qc mismatch always causes hypoxemia
4. Supplemental oxygen helps when there is a Va/Qc
mismatch. If O2 sats are low and supplemental oxygen does
nothing, a Shunt is suspected.
Shunt (when there is zero ventilation of bloodflow e.g. blockage of a
major bronchiole. Va/Qc = 0)
1. A region of lungs receiving no ventilation but is perfused
w/blood
a. Va/Qc of the region = 0
b. Described as intrapulmonary right-to-left shunt
c. Unlike Va/Qc mismatch, right-left shunt is not
amenable to O2 therapy
2. Right-to-left shunts normally occur to a small extent because
2% of cardiac output bypasses the lungs.
a. These shunts ALWAYS decrease arterial PO2
because of the admixture of venous blood with arterial
blood
b. The magnitude of a shunt can be estimated by having
a patient breathe 100% O2 and measuring the degree
of dilution of Oxygenated blood by nonoxygenated
shunted (Venous) blood.
3. Left-to-right shunts are more common, because pressures
are higher on the left side of the heart.
a. Usually caused by congenital abnormalities (patent
ductus arteriosus) or traumatic injury
b. Do not result in decreased PAO2. ​Instead, PO2 will
be elevated on the right side of the heart b/c there has
been an admixture of arterial and venous blood.
4. Inspired oxygen concentration increases arterial PO2, not
blood PO2
PAO2
High altitude
Decreased
Normal
Hypoventilation
Decreased
Normal
Diffusion defect (i.e.
Fibrosis)
Decreased
Increased
V/Q Defect
Decreased
Increased
Right-to-Left shunt
Decreased
Increased
iii.
iv.
Hypoventilation of non-pulmonary origin
1. Conditions in which the ​entire lung is hypoventilated
a. CNS depression (coma)
b. Neuropathies (MS)
c. Skeletal d/o (kyphoscoliosis)
d. Muscular d/o’s (myasthenia gravis)
e. Morbid obesity
2. The preceding ​always lead to hypoxemia
3. Supplemental O2 will increase PaO2
Origin of V/Q mismatch
1. Result of O2-Hb binding curve
2. It is not linear
3. It is the major carrier of O2 in blood
4. Saturation of Hb at “normal” pO2 leads to little advantage of
high pO2: cannot compensate for low O2 in one area by
increasing pO2 in other areas
5. V/Q ratio in airway obstruction is zero, if the airways are
completely blocked. That’s a shunt, yo.
6. V/Q ratio in a pulmonary embolism that totally blocks
bloodflow to a region of the lung is infinity. That’s called dead
space, bruh.
Normal
Airway Obstruction
(shunt)
Pulmonary
space)
V/Q
0.8
0
Infinity
PAO2
100 mmHg
-
150 mmHg
PACO2
40 mmHg
-
0 mmHg
PaO2
100 mmHg
40 mmHg
-
PaCO2
40 mmHg
46 mmHg
-
v.
vi.
Bohr effect: a shift in position of O2-Hb curve to the left indicates
increased affinity of O2 for Hb (fetal Hb doesn’t bind 2,3-DPG, and
is shifted to the left)
1. Decreased P50 (increased affinity):
a. Lower temperature
b. Lower pCO2
c. Lower 2,3-DPG
d. Increased pH
2. Increased P50 (decreased affinity):
a. Higher temp
b. Higher pCO2
c. Higher 2,3-DPG levels
d. Lower pH
3. Under resting and normal physiological conditions, Oxygen
P50 value for human blood is 28 mmHg
Diffusing capacity of the lung for O2
1. Minute Ventilation = Tidal Volume x Breaths/min
2. Alveolar ventilation = (tidal volume - dead space) x
Breaths/minute
3. Diffusing Capacity (DL) indicates how many ml of O2 diffuse
across lung per minute for a certain gradient - analogous to
a conductance. Determined by
a. Surface area available for gas exchange
b. Solubility of O2
c. Diffusivity of O2
d. Distance O2 molecule must travel (alv. To RBC)
e. These are combined for form diffusing capacity of
lung for O2: DL(O2) = ml O2/min/mmHg
4. Thus for each mmHg partial pressure gradient between
alveolus and capillary (PaO2-PcapO2) the DL(O2) describes
the diffusion of O2 into blood
a. Diffusing capacity = (PaO2-PcapO2)*DL(O2)
i.
vii.
DL(O2) decreased in many lung diseases:
emphysema, fibrotic lung disease, pulmonary
edema
ii.
DL(O2) is ​increased s​ lightly in exercise
iii. The DL(O2) must be corrected for the
hematocrit
5. CO2 transport
a. Dissolved CO2 (responsible for PCO2)
b. Carbamino compounds (CO2 reacts with free amino
group on Hb)
c. HCO3- (both in RBC and plasma)
i. Most CO2 produced by metabolism is carried
in the plasma in the form of HCO36. CO2 transport, blood
a. Produced by cellular metabolism, diffuses into the
blood where it is carried in 3 different forms
i. 63% as bicarbonate
b. Shape of CO2 dissociation curve implies that Va
significantly affects CO2
c. Hyperventilation lowers PACO2, PaCO2 and total
CO2 content (vol%) of blood
7. CO2 transport, Hb
a. Hydration of CO2 and dissociation of H2CO3 results
in generation of large quantities of HCO3- and H+
within the RBC. The HCO3- exchanges for Clb. Conditions in which entire lung is hypoventilated
always leads to CO2 retention (coma, MS,
myasthenia gravis..)
8. Va/Qc ratio
a. Low Va/Qc means insufficient air in an alveolus for
the amount of blood
b. High Va/Qc means too much air in an alveolus for the
amt of blood (Va/Qc can approach infinity) - so even
though there may be high PO2 in the air of that
alveolus, it cannot contribute to gas exchange (​it
Gravitation effects on flow
1. Cause of regional variation in distribution of ventilation
a. IPP is less negative at the base than at the apex
2.
3.
4.
5.
6.
b. Alveoli at base are relatively more compressed at
FRC
Compliance changes
a. For the same changes in IPP, has bigger effect on
volume at the base, compared to the apex
Regional variation in bloodflow
Ventilation/Perfusion ratio: upright position
a. When thorax upright, more air AND blood goes to the
base of the lungs than to the apex
b. BUT, More blood than air goes to the base
c. Alveoli at base are relatively hypoventilated for the
amount of blood, giving low Va/Qc at base ( < 1)
d. Alveoli at apex receive too much air for amt of blood
perfusing them, resulting in high Va/Qc at apex (~ 3!)
e. Alveolar ventilation at apex is ~ 0.24 L/min, whereas
at base is ~ 0.83 L/min
Ventilation/perfusion ratio: blood gases
a. If PCO2 is high (approaches 50mmHg), PO2 must be
low and VA/Qc ~ 0
i. In this scenario, ventilation of alveoli is blocked
b. PCO2 is very low, PO2 must be high and VA/Qc ->
infinity
i. In that scenario, ventilation is normal but blood
flow to alveoli is blocked
c. Normal: PCO2 is ~ 40mmHg, PO2 ~ 100mmHg in
alveolus
a. Increase in Alveolar-Arterial gradient for O2 above the
normal value indicates a VA/Qc mismatch
i. The greater the mismatch, the larger the A-a
ii.
The normal value is about 10mmHg
representing arterial blood that normally
by-passes pulmonary gas exchange
b. If ​gas ​from an alveolus with a high PO2 mixes with
gas from an alveolus with a low PO2, the PO2 in the
resultant gas mixture is the arithmetic mean
c. If ​Blood ​with high PO2 + blood with low PO2 mix,
PO2 in mixture is LESS than the arithmetic mean (a
direct consequence of the shape of the HbO2
dissociation curve)
7. A-a gradient for O2: normal pulmonary function
a. At apex; PAO2 = 130mmHg. At base; PAO2 =
70mmHg
i. Predicted PaO2: 100mmHg
ii.
Actual PaO2: 90mmHg ​(A-a gradient is
10mmHg)​
8. A-a gradient for O2: Pulmonary disease
a. A-a gradient can increase if an area of the lung is
underventilated, such that PaO2 = 60mmHg -> A-a
i. These numbers would indicate a shunt
b. If the gradient decreases when supplemental oxygen
is given, then V/Q mismatch is the cause, rather than
intrapulmonary shunt
9. Ventilation-perfusion abnormalities
a. Pulmonary embolus: ​clinical presentation depends
on nature of embolic material
i. Talc granules or cotton fibers (from illicit drug
usage), sickled RBCs, bloodborne parasites
(schistomiasis) lead to a slowly progressive
disease similar to pulmonary htn
ii.
Embolization of air, fat or amniotic fluid alters
pulmonary capillary membrane integrity and
presents as ARDS (acute respiratory distress
syndrome: local lung injury mediated by
neutrophils leading to multiple organ failure)
b. Most common cause of pulmonary emboli is
theomboemboli originated in deep iliofemoral veins
i. Consequence depends on amt of clot reaching
lung
c. A clot that almost completely occludes a small
number of vessels
i. High Va/Qc ratio in small number of lung units.
ii.
Small amt of blood diverted to rest of lung
1. Va/Qc of these units exhibit a minor
decrease
2. Peripheral arterial PO2 and PCO2
remain normal
iii. Large clot that breaks up en route to lungs and
occludes a large number of vessels
1. Large vol of blood diverted to
non-embolized units, substantially
lowers Va/Qc ratio of these units
a. Arterial hypoxemia common
b. Correction of hypoxemia
requires hyperventilation, may
result in marked hypocapnia
iv. Chronic bronchitis: V/Q mismatch leads to
often severe hypoxemia, CO2 retention (esp.
In later stages), increased A-a gradient for O2
and low tolerance for exercise
v.
Emphysema: in addition to reduction in
flow-related measurements and hyperinflation
of lung common to other obstructive diseases,
loss of pulmonary capillaries results in
decrease in the DLO2
8. Diffusion vs. Perfusion limitations
a. N2O diffuses very rapidly and equilibrates across pulm. Capillary in ~
0.1 sec. It equilibrates fully by the time the perfusing blood leaves
the capillary; -> perfusion-limited gas exchange
i. O2 and CO2 are perfusion-limited (O2 can equilibrate within
0.25sec, even though transit through capillary is 0.75sec)
ii.
Only in abnormal lung does the blood not equilibrate with
alveolar gas
b. A gas such as CO binds avidly to H with reaction time faster than the
rate of diffusion
c.
9. Lung Diseases
a. Asthma - ​obstructive disease that impairs expiration
i.
Characterized by decreased FVC, FEV1 and decreased FEV1/FVC
ii.
FRC increases b/c of air trapping
b. COPD - ​combination of chronic bronchitis and emphysema. An obstructive
disease with increased lung compliance that impairs expiration
i.
Also characterized by decreased FVC, FEV1 and FEV1/FVC
ii.
Air trapping occurs, increasing FRC and creating barrel chest
c. Fibrosis - ​restrictive lung disease with ​decreased lung compliance
impairing ​inspiration. ​Characterized by ​decrease in all lung volumes.
FEV1/FVC increases, because FEV1 decreases less than FVC
d. Sarcoidosis - ​symptoms include (but can vary, depending on organs
involved)
i.
Persistent dry cough
ii.
Shortness of breath
iii. Wheezing
iv.
Chest pain
e. Flow-Volume curves
i.
Tracheal Stenosis: ​can take 5-6 seconds for most air to be
released. Flow rates are very low; no sharp ‘peak’ in flow rate
would be observed
ii.
Restrictive Disease: RV and FVC are low, but the flow rates for a
given lung volume are ​higher​ (all lung volumes are reduced)
iii. Obstructive Lung disease: flow rates are lower for a given lung
volume. Slope of the F-V curve is decreased, as well.
Control of Ventilation Lecture
● Respiratory center in the Medulla - Central control of ventilation. Is located in the
reticular formation.
○ Breathing in/out; the inspiratory component and expiratory component send
efferents to the diaphragm and intercostals to drive breathing. Reciprocal
inhibition of each component gives rise to inherent rhythmicity.
○ The Apneustic center stimulates the inspiratory component to breathe, and is itself
regulated by the pneumotaxic center. Negative feedback from the inspiratory
component stimulates the pneumotaxic center, ​inhibiting t​ he apneustic center.
○ Peripheral reflexes communicate with CR, I, and APN. Notably, the
Hering-Breuer reflex is initiated during large inspirations via mechanoreceptors to
prevent overinflation of the lungs; the Apneustic center is activated, directly
inhibiting the Inspiratory center of the medulla.
○ Some chemoreceptors are found in the chemosensitive area of the medulla, which
counters changes in blood pH by monitoring CO2 levels
■ A decrease in blood pH is usually caused by increased CO2 levels. This
causes breathing rates to increase.
■ Note: the central chemoreceptors’ response to CO2 (or [H+]) is much
more important physiologically than the peripheral chemoreceptors’
response to CO2.
○ Other types of receptors for control of breathing
■ Lung stretch receptors
● Located in the smooth muscle of the airways
● When stimulated by lung distension, these receptors produce
decrease in breathing frequency (Hering-Breuer reflex)
■ Irritant receptors
● Located between the airway epithelial cells
● Are stimulated by noxious substances (e.g. dust and pollen)
■ J (juxtacapillary) receptors
● Located in alveolar walls, close to capillaries
● Engorgement of the pulmonary capillaries, such as may occur with
left heart failure, ​stimulates the J receptors, causing rapid,
shallow breathing
■ Joint and muscle receptors
● Activated during movement of limbs
● Are involved in early stimulation of breathing during exercise
● Spinomedullary transection abolishes phrenic nerve activity -> afferents to the phrenic
●
●
nerve originate in the medulla.
○ In contrast, pontomedullary transection does not affect phrenic nerve activity (or
CN XII activity)
Pre-Botzinger complex: essential for the generation of respiratory rhythm.
Properties of the DRG and VRG
○ Dorsal Respiratory Group (DRG): generates the basic rhythm for breathing,
primarily ​inspiration​​.
■ Receives input from the vagus and glossopharyngeal nerves.
● Vagus relays info from the peripheral chemoreceptors and
mechanoreceptors in the lung.
● The glossopharyngeal nerve relays info from peripheral
chemoreceptors.
■ Stimulated by the ​apneustic center
● Apneustic center is located in the lower pons. Stimulates
inspiration, producing a deep and prolonged inspiratory gasp
(apneusis)
■ Inhibited by the pneumotaxic center.
● Pneumotaxic center is located in the upper pons. Inhibits
inspiration, and therefore regulates inspiratory volume and
respiratory rate.
■ The rhythm of the DRG generates ~ 12-16 breaths/minute in humans,
with inspiration = 2 sec, expiration = 3 sec.
■ Sends output to the diaphragm
○ Ventral Respiratory Group (VRG): contains both inspiratory and expiratory
neurons.
■ Primarily responsible for ​expiration
■ Is not active during normal, quiet breathing, when expiration is
●
●
●
passive. Is only active when expiration becomes active (e.g.
exercise, hypoxemia)
Inspiratory output and Expiratory Output
○ Inspiratory
■ DRG efferents -> Phrenic nerve -> diaphragm
■ Pre-BotC efferents -> spinal motor neurons -> inspiratory intercostal
muscles
○ Expiratory
■ VRG efferents -> spinal motor neurons -> output to the ​expiratory
intercostal and abdominal muscles ​(which are only engaged during
exercise or hypoxia)
Pacemaker cells in the PreBot Complex
○ the interneurons of the PreBotC include pacemaker cells with spontaneous
bursting activity.
Rhythmicity of inspiration and expiration
○
●
●
● CSF pH is strongly inversely correlated with alveolar ventilation
● The chemosensitive area of the medulla is stimulated by H+ ions in CSF, ​most of which
derive from CO2. High [H+]csf triggers the chemosensitive area to stimulate the brain
stem inspiratory area, which is very close (fraction of a millimeter) in proximity.
● Steady-state pH of CSF is strongly correlated with the pH of arterial blood. Both
metabolic and respiratory acid-base changes are influential, but respiratory acid-base
changes are much ​more s​ o.
○ Metabolic acidosis/alkalosis has less effect on CSF pH because CO2 crosses the
BBB, but H+ and HCO3- do not (as much)
○ CO2 diffuses b/c it’s lipid-soluble, allowing it to cross BBB. Once in the CSF, it
combines with H2O to re-form bicarbonate and H+; the H+ ions then act directly
on the central chemoreceptors
○ Increases in PCO2 and [H+] stimulate breathing, while decreases in PCO2 and
[H+] inhibit breathing. The resulting hyper- or hypoventilation then returns
arterial PCO2 towards normal.
Type of chemoreceptor
Location
Stimuli that increase
breathing rate
Central
Medulla
Low pH (of CSF), Increased
PCO2
Peripheral
Carotid and Aortic bodies
Low PO2 (if < 60 mmHg),
Increased PCO2, Low pH
● The body uses a number of reflexes to control breathing
○
● Integrated responses of the respiratory system
○ During exercise, ventilatory rate increases to match increased O2
consumption and CO2 production by the body. The stimulus for increased
vent is not totally understood, but joint and muscle receptors are activated
during movement that cause increase in breathing rate at the beginning of
exercise.
○ Mean values of arterial PO2 and PCO2 do not change during
exercise.
■ Arterial pH doesn’t change during moderate exercise, but may
decrease during strenuous exercise because of ​lactic acidosis
○ On the other hand, venous PCO2 increases during exercise b/c of excess
CO2 produced by the exercising muscle
○ Pulmonary blood flow increases ​b/c cardiac output increases during
exercise; so more pulmonary capillaries are perfused, and more gas
exchange occurs. ​The distribution of V/Q ratios during exercise is
more even than at rest, ​and there is a decrease in physiologic dead
space.
○ Alveolar PO2 is decreased b/c barometric pressure is decreased (so
arterial PO2 is also decreased -> hypoxemia)
○ Hypoxemia stimulates peripheral chemoreceptors to trigger
hyperventilation, producing respiratory alkalosis. Can be reversed by
○ Hypoxemia stimulates renal EPO production, resulting in RBC production
increases and thus increased Hb concentration, increased O2-carrying
capacity of blood, and increased O2 content of blood.
○ 2,3-DPG concentrations increase, shifting O2-dissociation curve to the
tissues
○ Pulmonary vasoconstriction, which increases pulmonary arterial pressure,
increasing the work of the right side of the heart against the higher
resistance -> right ventricular hypertrophy
Questions from Thompson Practice
Problems
● Practice test
○ 3. Which of the following statements would be true of an Intrapleural
Pressure (IPP) measurement taken during the Experimental period as
compared to the Control period?
■ A.IPP would be more negative at the end of inspiration
■ B.IPP would be the same at the end of inspiration
■ C.IPP would be more positive at the end of inspiration
■ D.IPP would be more negative at the end of expiration
■ E.IPP would be more positive at the end of expiration
○ 20. Resting IPP (just prior to the onset of inspiration) is more negative
than normal
■ A. True of X
■ B. True of Y
■ C. True of both X and Y
■ D. Not true of X or Y
● Version 1
● Version 2
17: As compared to normal, all of the following are true, EXCEPT
■ A. The FEF25-75 is increased.
■ B. The FEV1sec is decreased
■ C. The FVC is decreased
■ D. The FEV1sec/FVC ratio is decreased
■ E. The inspiratory capacity is decreased
http://www.physiologyweb.com/.search?results_page=http%3A%2F%2Fwww.physiolog
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Practice questions, BRS Respiratory
- (A) Forced expiratory volume/forced vital capacity (FEV1/FVC) is increased
- (B) Ventilation/perfusion (V/Q) ratio is increased in the affected areas of his lungs
- (C) His arterial PCO2 is higher than normal because of inadequate gas exchange
- (D) His arterial PCO2 is lower than normal because hypoxemia is causing him to
hyperventilate
- (E) His residual volume (RV) is decreased
7. Which volume remains in the lungs after a tidal volume (TV) is expired?
- (A) Tidal volume (TV)
- (B) Vital capacity (VC)
- (C) Expiratory reserve volume (ERV)
- (D) Residual volume (RV)
- (E) Functional residual capacity (FRC)
- (F) Inspiratory capacity
- (G) Total lung capacity
18. Compared with the apex of the lung, the base of the lung has
- (A) a higher pulmonary capillary PO2
- (B) a higher pulmonary capillary PCO2
- (C) a higher ventilation/perfusion (V/Q) ratio
- (D) the same V/Q ratio
23. Which of the following causes of hypoxia is characterized by a decreased arterial
PO2 and an increased A–a gradient?
- (A) Hypoventilation
- (B) Right-to-left cardiac shunt
- (C) Anemia
- (D) Carbon monoxide poisoning
24. A 42-year-old woman with severe pulmonary fibrosis is evaluated by her physician
and has the following arterial blood gases: pH = 7.48, PaO2 = 55 mm Hg, and PaCO2 =
32 mm Hg. Which statement best explains the observed value of PaCO2?
- (A) The increased pH stimulates breathing via peripheral chemoreceptors
- (B) The increased pH stimulates breathing via central chemoreceptors
- (C) The decreased PaO2 inhibits breathing via peripheral chemoreceptors
- (D) The decreased PaO2 stimulates breathing via peripheral chemoreceptors
- (E) The decreased PaO2 stimulates breathing via central chemoreceptors
25. A 38-year-old woman moves with her family from New York City (sea level) to
Leadville Colorado (10,200 feet above sea level). Which of the following will occur as a
result of residing at high altitude?
- (A) Hypoventilation
- (B) Arterial PO2 greater than 100 mm Hg
- (C) Decreased 2,3-diphosphoglycerate (DPG) concentration
- (D) Shift to the right of the hemoglobin–O2 dissociation curve
- (E) Pulmonary vasodilation
- (F) Hypertrophy of the left ventricle
- (G) Respiratory acidosis
26. The pH of venous blood is only slightly more acidic than the pH of arterial blood
because
-
(A) CO2 is a weak base
(B) there is no carbonic anhydrase in venous blood
(C) the H+ generated from CO2 and H2O is buffered by HCO3 – in venous blood
(D) the H+ generated from CO2 and H2O is buffered by deoxyhemoglobin in
venous blood
(E) oxyhemoglobin is a better buffer for H+ than is deoxyhemoglobin
```