Transcript Silverthorn: Human Physiology (1st ed.) Ch 18: The Kidneys

Pulmonary Physiology:
Electron micrograph showing a pulmonary
capillary (C) in the alveolar wall.
Figure 4.02. Changes in cross-sectional area
of airways through successive generations of
branchings
The Pulmonary Tree with some blood vessels as seen in a "corrosion"
preparation: 1 = trachea; 2 = left principal bronchus; 3 = right principal
bronchus; 4 = aorta, 5 = thoracic aorta; 6,7,8 = bronchial arteries.
Scanning electron micrograph of a section of lung showing
many alveoli and a small bronchiole
Lung Composition. Left: Percentages of liquids and solids on a weight
basis; Right: Percentages of gas, liquids and solids on a volume basis
To understand how the values of the partial pressures of the three
respiratory gases change from the point of inspiration, through the
"respiratory compartments" - to the expiration point, including the FRC's
buffer role.
The Ventilatory Cycle, showing
Tidal Volume.
Figure 1.01. Standard (static) lung volumes as measured with
a spirometer
Another graphical representation of
Lung Volumes
Table 1.01. Standard lung volume
values.
Figure 1.02. A Forced Ventilatory Capacity (FVC) recording on which the
volumes expired at the end of 0.5, 1, 2 and 3 seconds are indicated
(FEV0.5, FEV1.0, FEV2.0, FEV3.0).
Figure 1.03. An FVC recording on which the points of 200 ml and 1200
ml of expired volumes are indicated. The slope of the line between these 2
points is the average flow rate during this period (called the FEF0.2-1.2L).
Figure 1.04. An FVC recording on which the 25% and 75% points of the
FVC have been indicated. The slope of the line between these 2 points is
the average flow rate during this period (called the FEF25-75%). The
same FVC maneuver is again used and the average flow rate during the
middle 50% of the FVC is shown (i.e. between points where 25% and
75% of the FVC has been expired).
Figure 1.05. Changes in the gaseous partial pressures from inspired
atmospheric air to expired gas (in mmHg).
Figure 2.03. Changes in lung volume, air flow, intrapleural pressure, and
alveolar pressure during normal (tidal) breathing. The dashed intrapleural
pressure line would be followed if there were no airway resistance). The
diagram at the left shows the lung and a spirometer measuring the changes
Figure 5.01. Effect on distribution of ventilation due to inspiration
from FRC (panel A) vs. starting from RV (panel B).
Table 6.01. Comparison of pulmonary and systemic hemodynamic
variables during rest and exercise of moderate severity in normal adult
man.
Figure 6.01. Pulmonary vs. systemic
circulation pressures (mmHg).
This diagram shows the virtual matching of blood flow (FLOWS) and air
flow (VOLUMES) within the normal lung.
Figure 6.02. Pulmonary vascular resistance (PVR) falls as the very
compliant (distensible) vessels are subjected to higher distending
pressures.
Table 6.02. Factors that when varied cause "passive" changes in
pulmonary vascular resistance (PVR) and the direction of the responses.
Figure 6.06. Four zone model of pulmonary circulation in which
hydrostatic arterial and venous pressures fall with increasing distances up
the 30 cm height of the lung. (a=arterial, A=alveolar, V=venous.)
Table 6.03. Important causes of "active" changes in pulmonary vascular
resistance (PVR) and the direction of the responses
Figure 7.01. Perfusion-limited (nitrous oxide = N2O & oxygen) transfer
of oxygen vs. diffusion-limited transfer (carbon monoxide = CO).
Figure 7.06. Hemoglobin-oxygen association-dissociation curve at pH 7.4
and 37o C.
Figure 7.07. Changes in the Hb-oxygen association-dissociation curve
with temperature, pH and 2-3 DPG.
Figure 7.08. Comparison of P80 of Quechua (Andes Mountains)
inhabitants with Western Europeans (sea level) under normal conditions
and after pH is lowered from 7.4 to 6.7. "Double effect" rightward shifts
of Quechuas aids unloading of oxygen from blood to tissues.
Figure 7.09. Loading of CO2 from tissure to blood and associated O2
release from blood to tissue.
Figure 7.10. Showing the relative importance of the three ways in which
CO2 is transported from the tissues to the lungs (right).
Figure 9.01. Characteristics of the four classical hypoxias compared with
the normal state (see Table 9.01 for more details).
Table 9.01. Classification of the causes of hypoxia in terms of alveolar
PO2, arterial P02, arterial oxygen content, venous P02, and venous
oxygen content. The last column indicates whether increased inspired
fractional oxygen will alleviate the problem
Figure 9.02. Comparison of the oxygen dissociation curves of normal
blood, blood containing 20%, 40% and 60% carboxyhemoglobin (COHb),
and blood from a severely anemic patient.
Figure 9.03. Increasing 2,3-diphosphoglyceric acid (DPG) concentration
causes the hemoglobin-oxygen association-dissciation curve to shift to the
right, ie. to decrease Hb's affinity for oxygen (P50 values are 15, 20, 27,
34, and 42 mm Hg from left to right).
Table 13.01. Mechanisms that contribute to the defense of the
respiratory tract
Figure 13.01. Mechanisms of aerosol particle deposition include
sedimentation via gravity, inertial impaction, and diffusion by Brownian
motion
Figure 13.02. Ciliary action and
mucous movement
Table 13.02. Pulmonary macrophage
functions.
Table 13.03. Summary of the fate of circulating substances during a single
passage through the intact pulmonary circulation.
Fig. 17-1
The Respiratory System
1) The lung -- two functional components:
Airways (convection of gas) (p. 550-2, 499-502, 475-7,
480; Fig. 17-2)
Alveoli (site of gas exchange or diffusion; (also
includes respiratory bronchioles and alveolar sacs) (p.
551, 502, 477; Fig. 17-2))
2) The pump muscles (p. 548, 500, 499-500, 476; Fig. 172a):
Inspiratory: diaphragm, external intercostals, other
accessory muscles when respiratory drive increases
Expiratory: internal intercostals, abdominals; typically
inactive at rest (in humans)
Consider flow from a tube at the bottom of a bucket:
The higher the level of water in the bucket, the greater the
pressure of the water at the bottom and, therefore, the
greater the flow. Therefore, flow is proportional to the
pressure gradient.
The greater the resistance of the tube, the less the flow.
Therefore, flow is inversely proportional to resistance.
Flow = Δ P/R
This is the most important equation you will need.
The pressure gradient and resistance determine flow
R
ΔP
Hydraulic version of Ohm's law used to determine electric
current flow through a circuit (see section related to membrane
potential) and is identical to that used to describe blood flow
(pp. 453-4, 408-10).
Flow to and from the alveoli depends on:
a) the resistance (R) to flow offered by
the airways (reflecting their size), and
b) the pressure generated (ΔP) by the
respiratory pump muscles.
Airway resistance: Depends on the physical
properties of the fluid (air) and the geometry of the
tubes (airways); given by Poiseuille's Law (p. 560,
513, 490):
R = 8 η l / π r 4 where:
η = the density of the fluid
l = the length of the tube
r = the radius of the tube.
r is the most important because it is raised to the
fourth power.
Airway resistance is controlled:
passively (lung volume, strength of
airway wall)
actively (degree of contraction of airway
smooth muscle).
Control of airway smooth muscle tone
.
(the “R” in V = ΔP/R)
(p. 560-1, 513-4, 490-1)
Depends on:
• sympathetic (dilator) and
• parasympathetic (constrictor)
activity in branches of the autonomic nervous
system.
Sympathetic (dilator) effects can be:
direct -- release of norepinephrine from sympathetic
terminals into the ganglia containing the parasympathetic
fibres, thereby reducing the level and/or effectiveness of
parasympathetic activity, or
indirect -- epinephrine released from the adrenal
medulla into the circulation, causes relaxation of airway
smooth muscle.
Parasympathetic (constrictor) effects are:
direct -- via release of acetylcholine from postganglionic
fibres directly onto airway smooth muscle.
Also depends on local levels of O2 and CO2 (p. R19-20
in notes; Fig. 17-17 p 576-7, 519, 497)
.
The “ΔP” in V = ΔP/R
Barometric pressure, PB (p. 552, 503, 480) -- the "weight" of
the atmosphere.
Pressures are relative to PB at sea level, PB = 760 mmHg
(or 1 ATA or 100 kPa or 1000 hPa or 1000 cmH2O)
The local (ambient) PB is set equal to zero; all other
pressures are relative to this value. Thus:
pressures > PB are positive
pressures < PB are negative
Units: most respiratory physiologists and clinicians still use
cmH2O. 1 mmHg = 13.6 mmH2O (mercury is 13.6 times as
dense as water) = 1.36 cmH2O
Fig. 17-5
The lung 'wants' to collapse (see below) and chest wall
'wants' to expand -- the pressure in the pleural space is
therefore subatmospheric or "negative"-- an average
value is -5 cmH2O.
Recoil (collapsing) pressure of the lung (p. 557-8, 510,
487-9; Fig. 17-10, 17-11)
- elastic recoil of tissues (25-35%)
- surface tension (65-75%)
Relations between Volume and Pressure
Compare the volume-pressure curves of the lungs when
filled with saline and with air.
The air-filled lung generates more recoil pressure
because of surface tension at the air-liquid interface.
Surface tension is only possible at a surface.
More pressure is required to inflate the air-filled lung.
The 'ease' with which volume can be changed is
expressed by the term compliance (p. 559, 511, 488); the
greater the compliance, the greater the change in volume
for a given pressure applied.
C = ΔV / Δ P (notes, p. R8)
Pressure-Volume Relations in Saline- and Air-Filled Lungs
P. R8
LaPlace's Law
relates recoil pressure, surface tension
and size
P=2T/r
where
P = internal pressure
T = tension in the wall of the
structure ( = surface tension)
r = radius of the structure
Unstable Bubbles and Stable Alveoli
p. 560, 512-3, 489-90
Surfactant: surface active (i.e., surface tension) causes
surface tension to vary with surface area.
Increased surface tension of a large alveolus offsets its
larger radius, making its recoil pressure equal to that of a
smaller alveolus (Fig. 17-11 right, 17-12 right). This prevents
small alveoli emptying into large alveoli.
Interdependence (not in Silverthorn): stabilization of
alveoli by the connective tissue between different parts of
the lung. One lung region cannot get smaller without
making another region larger.
x
x
x
x
Relevance of Surfactant
Surfactant reduces surface tension and thereby
reduces work of breathing. It allows our alveoli to
remain expanded to maintain gas exchange.
Without it, our alveoli would collapse and gas
exchange would deteriorate rapidly.
As happens in . . . .
Natural and artificial replacements for surfactant
are now routinely administered to premature
infants.
Relevance of LaPlace's Law
• why capillaries are so "strong"
• bicycle and automobile tires
Rearrange LaPlace’s Law to get
T=P × r
(The strength (T) of the wall of the structure
needed to withstand the product of the internal
pressure and the radius of the structure)
Respiratory Mechanics
At end-expiration (functional residual capacity, FRC),
the chest wall ‘wants’ to expand (p. 558, 510-1, 487-8),
like a compressed spring back to its longer resting
position.
FRC: volume of the respiratory system at normal
end-expiration. It is important for two major reasons:
1) The lung remains ~35% filled, allowing gas
exchange to continue during the interval between
breaths.
2) Respiratory system compliance is maximal at
FRC. Thus, work of breathing is minimal at this
volume.
Mechanics of the Respiratory System
most compliant part of curve
P. R9
Mechanics of the Respiratory System
P. R9
Transmural Pressures
At end-expiration (FRC), the tendency of the chest wall to
expand is equal and opposite to the tendency of the lung
to collapse. This relation is described by considering the
three pressures acting at the lung surface:
Pl is the elastic recoil pressure of the lung tissue
Ppl is the pleural pressure
PA is the pressure in the alveolus (= PB when flow is zero)
The pressure difference across the wall of a structure, the
transmural pressure, equals the internal pressure less the
external pressure.
Transmural pressure =
internal pressure - external pressure, or
Transmural pressure =
alveolar pressure - pleural pressure
Therefore: Pl = PA- Ppl
At end-expiration ( = 0 ),
PA = 0 cmH2O
Ppl = -5 cmH2O (Silverthorn -3 mmHg),
Pl = 0 - (-5) = +5 cmH2O
Note: Pl must be equal and opposite to Ppl to give
.
PA = 0 cmH2O (required for V = 0)
Inspiration
To produce inspiratory flow, PA must be negative
(subatmospheric). Rearranging the equation:
PA = Pl + Ppl
Thus, alveolar pressure (PA) is the sum of elastic recoil
pressure (Pl) and pleural pressure (Ppl).
To make PA 'negative,' Ppl must be more negative than
Pl is positive. When the diaphragm (p. 507, 485),
contracts, it descends, lowers Ppl, decompresses the
gas in the lungs and, therefore, makes PA 'negative.'
This causes inspiratory flow.
A model to illustrate this is shown in the Figure (p. R11), in
which the elastic recoil pressure of the balloon is
designated as the transpulmonary pressure (Ptp). In this
example, PA = Ptp + Ppl
Because of the resistance to airflow, lung expansion lags
the pressure which causes inspiratory flow. Therefore, as
long as inspiratory muscles contract enough to cause flow,
the elastic recoil of the lung, Pl, will not 'catch up' to the
more negative Ppl.
When inspiratory muscle (diaphragm) contraction
eventually decreases, Pl does catch up to and equals Ppl
(but now, for example, Ppl = -8 cmH2O and Pl = +8
cmH2O). Because PA = Pl + Ppl, therefore, PA = +8 + (-8)
= 0 cmH2O. Inspiration now stops.
-5
0
-10
pressure
(cmH2O)
Page R11
-5
-10
0
Ptp
PA
Ppl
rest (end-expiration)
inspiration
Relation between PA and Flow
As flow decreases towards zero, the pressure needed
to produce flow approaches zero regardless of
resistance.
.
Rearranging V = ΔP/R gives
.
ΔP = V R
Thus, PA would hardly change during inspiration; i.e.,
the tracing of PA would be 'flat' (red line at ~PB or "0"
mmHg) (Fig. 17-9, 17-10, top right; same figure in 1st
edition but the tracing is called intrapulmonary pressure).
Moreover, the tracing of Ppl would be straight (red line),
not curved, lines. Because some pressure is needed (and
occasionally a lot) to overcome flow resistance, not just to
expand the lung (i.e., overcome its elastic recoil), PA falls
below PB (subatmospheric) during inspiration and above
PB (supra- atmospheric) during expiration.
This is also why the tracing of Ppl is slightly concave to
the time axis.
Were the subject to breathe faster (e.g., blue line), both
lines would deviate even more because of the extra
pressure required to overcome the increased flow
resistance.
Fig. 17-9 17-10
pressure trajectories with infinitely slow
inspiration or if flow resistance (R) is zero
pressure trajectory at higher flow
The reason why the pressure curve is straight for the Ppl
and flat (at zero) for the PA can be explained using the
basic equation
.
V = ΔP / R
Rearranging:
.
ΔP = V • R
.
For a given R, as the flow (V) decreases towards zero, ΔP
must also decrease towards zero.
This ΔP is the flow resistive component of the total
pressure required to change lung volume. Therefore, Ppl
still falls from –5 to –8 cmH2O but this reflects only the
elastic, not the flow-resistive, component.
EXPIRATION
In resting humans, we just stop breathing in and
relax. Recoil energy stored in the lung generates
expiratory flow.
Thus, at the onset of expiration, Ppl becomes
slightly less negative, say -7.9 cmH2O. But Pl is still
8 cmH2O. Therefore,
PA = Pl + Ppl = +8 + (-7.9) = +0.1 cmH2O.
In other words, PA > PB ; expiratory flow starts.
Dynamics of Flow
Expiratory Flow Limitation (not in
Silverthorn; p. R13 in notes
Objectives: see notes, p. R13
Pressures and Flows during Breathing
Pressures and Flows during Breathing
normal expiration
0
+1
cough
+108
0
Flow, Linear Velocity and Cross-Sectional Area
Appendix 3, Equation 6
flow (cm3/s) = cross-sectional area (cm2) × velocity (cm/s)
If flow remains constant but cross-sectional area decreases,
linear velocity of the gas must increase.
In cough and sneeze, this is important because the kinetic
energy of the expired gas must increase in order to have
sufficient energy to move debris in the airways.
Kinetic Energy = ½ mass × velocity2
Fig. 17-13 (17-14)
Optimization of O2 Delivery to Alveoli
The lungs have two ventilatory functions -- move gas to
and from the alveoli (convection) and provide a surface for
gas exchange (diffusion). To optimize convection, the
airways should be as large as possible (minimal resistance
to flow). To optimize diffusion, there should be as many
alveoli as possible (maximal area). These goals are
incompatible; the lungs we have represent a compromise
between alveolar and airway volume. When mammals
breathe in, some gas stays .in the airways -- the anatomic
.
dead space VD (which affects alveolar ventilation, VA -- p.
565, 516, 494).
.
.
Effects of varying VT and f on VE and VA
VT (mL) f (bpm) VD (mL)
.
VE (L/min)
.
.
.
.
.
VA (L/min) VD/VE VA/VE
rest
500
12
150
6.00
4.20
0.30
0.70
rest
300
20
150
6.00
3.00
0.50
0.50
rest
750
8
150
6.00
4.80
0.20
0.80
rest
150
40
150
6.00
0
1.00
0.00
exercise
mod.
1000
20
150
20.00
17.00
0.15
0.85
heavy
1500
30
150
45.00
40.50
0.10
0.90
Table 17-4
.
If maximizing VA represents the primary objective
of breathing, then the ideal breathing pattern
should consist of slow deep breathing pattern,
when VT >> VD. (Indeed, during exercise, VT
increases but VD does not, resulting in less
"wasted ventilation".) But we do not breathe this
way because of the
work of breathing
Work of Breathing
.
For a given VA, one can use any combination of VT and
f (p. 565, 517, 495); instead, we use a limited range of
both. A low f and a high VT are associated with a low
flow-resistive component but a high elastic component
of the work of breathing; in contrast, a high f and a low
VT are associated with a high flow-resistive but a low
elastic component of the work of breathing. We use a
combination of f and VT that minimizes the total of
these two components. The f we use at rest and which
results in minimal work of breathing ranges from 8 to 16
breaths per minute.
Work of
breathing
(at
. fixed
VA)
total work
flow-resistive work
range used
elastic work
Respiratory Frequency
Gas Exchange
p. 576-9, 519-21, 496-9
(see also p. 134-6, 118-20, 117-20)
Gas Exchange
• diffusion of O2 from alveoli to pulmonary capillary
blood
• diffusion of CO2 in the reverse direction.
Principles of diffusion are identical to those of convective
flow:
• a pressure gradient ( ΔP)
• a resistance, R, related to the physical properties of the
gas and the structures through which it diffuses.
For diffusion, ΔP is not hydraulic but based on the partial
pressure of the gas (see below).
Fig. 18-2 17-6
Fig. 18-2 17-6
Fig. 18-2 17-6
Fig. 18-2 17-6
The basic equation is:
.
Vgas = ΔP / R
R: for both O2 and CO2
R = T / AD
Where
A is the surface area available for diffusion
D is the diffusion constant for O2 or CO2, and
T is the thickness of the alveolar-capillary membrane
Since D is constant for each gas,
R=T/A
(see p. 575, 3rd edition)
ΔP :
- 2
for O2, ΔP = PAO2 - PvO
- 2 - PACO2
for CO2, ΔP = PvCO
Therefore:
.
- 2) x A D / T
VO2 = (PAO2 - PvO
and
.
- 2 - PACO2) x A D / T
VCO2 = (PvCO
.
.
where VO2 and VCO2 are the diffusion rates of O2 and
CO2.
.
These equations are another form of V = ΔP/R, where:
- 2) for O2,
ΔP = (PAO2 - PvO
- 2 - PACO2) for CO2
or (PvCO
~
R, referring to gas flux across a surface rather
than bulk flow through a tube, is related to the
• Area for diffusion ( ~ radius of tube,
Poiseuille's Law)
• Thickness of the alveolar-capillary
membrane ( ~ length of tube, Poiseuille's Law)
• Diffusibility of the gas (~ viscosity of the
fluid, Poiseuille's Law)
In summary, we have:
a ΔP term (the gradient), and
a structural resistive term (T/A = thickness/area)
which determines how easily the gas diffuses.
Because D for O2 and CO2 do not change, the only
factors which affect diffusion of either gas are
changes in:
- 2 (for O2)
PAO2 or PvO
- 2 (for CO2)
PACO2, PvCO
T, the diffusion distance
A, the surface area
Partial Pressure Gradients p. 576-7, 520-1, 497-8
OXYGEN In dry air, the PO2 depends on its concentration
in air, which is ~21% or 0.21. If PB = 760 mmHg, then the
partial pressures of all gases must sum to 760 mmHg.
Therefore, the PO2 is 0.21 x 760 = 160 mmHg (Dalton's
Law of Partial Pressures) (p. 552-3, 503-4, 481).
During inspiration, the gas is saturated with H2O: at 37C,
the PH2O is 47 mmHg. Therefore, all the other gases,
including O2, must add up to 760-47 = 713 mmHg. Since
O2 occupies 0.21 of this, the PIO2 = 0.21 x 713 mmHg =
150 mmHg (p. 553, 504, 481).
In the alveoli, CO2 is also present. The PACO2 is ~40
mmHg. This reduces the PAO2 to ~100 mmHg (Silverthorn
does not deal with this issue; p. 576, 520, Table 18-1, 17-7; not in 1st
edition).
Page R18
This value, 100 mmHg, represents the top end of
the gradient causing diffusion of O2 into the
pulmonary capillary blood.
At rest in a normal individual, the lower end of the
gradient (i.e., in the mixed venous ( v- ) blood, in the
pulmonary artery and the start of the pulmonary
- 2 = 40 mmHg).
capillaries) is ~40 mmHg (PvO
Therefore, the gradient for diffusion of O2 is
100 - 40 = 60 mmHg.
CARBON DIOXIDE
CO2 originates from metabolically active tissues. In the
pulmonary artery (mixed venous blood) before
- 2 is ~46 mmHg.
oxygenation occurs, the PvCO
This represents the top end of the gradient causing
diffusion of CO2 from the pulmonary capillary blood to
the alveoli, for subsequent exhalation.
Since the PACO2 is 40 mmHg, the gradient for
diffusion of CO2 = 46 - 40 = 6 mmHg.
Note: Although almost as much CO2 diffuses from the
blood to the alveoli as O2 diffuses from the alveoli to
the blood, CO2 requires a gradient of only 6 mmHg
compared to the 60 mmHg) required for O2. Why?
Effects of Airway and Blood Gases on
Distribution of Gas and Blood Within the
Lung
(p. 566-7, 518, 496-7; Table 17-6; Figure 17-16, 17-17)
Dynamics of Diffusion
(p. 576-7, 519, 497)
Transport of O2 and CO2 by Blood
(p. 579-87, 522-9, 500-6)
Alveolar Gas Pressures: the Bathtub Analogy
Oxygen
Page R19
Alveolar Gas Pressures: the Bathtub Analogy
Carbon Dioxide
Page R19
Page R20
Fig. 17-16, 17-17
Fig. 17-16, 17-17
bronchodilation
bronchoconstriction
vasoconstriction
vasoconstriction
PO2 and
PCO2
PO2 and
PCO2
OXYGEN
Air contains about 21% O2, or about 210 ml O2 per litre of
air; plasma, a water based solution, equilibrated with gas
with a PO2 of 100 mmHg contains only 0.3% O2, or about
3 ml O2 per litre plasma.
At this concentration, delivering enough O2 to satisfy
metabolic requirements would require a cardiac output of
~100 L/min, a value ~20 times that at rest and about triple
the maximum during severe exercise.
Evolution has solved this problem in 'higher' animals by
increasing the carrying capacity of blood with erythrocytes
containing haemoglobin which reversibly binds O2.
Each litre of blood contains ~150 g of haemoglobin and
each gram of haemoglobin binds 1.34 ml O2; therefore, a
litre of blood, in addition to any dissolved O2, can bind
about 200 ml O2.
Thus, 1 litre of blood carries about the same amount of
O2 as 1 litre of air. More than 98% of this O2 is carried in
chemical combination as HbO2 (p. 579, 522-3, 500, Fig.
18-7, 17-20) (actually, because each molecule of Hb can
combine with 4 molecules of O2, a better representation
is Hb(O2)4 (see p. 581, 523, 501).
Note: the PO2 of the blood is due ONLY to dissolved O2,
not to chemically combined O2. In an organism without
Hb, the PaO2 would still be the same, about 100 mmHg.
O2 combined with Hb does NOT contribute to the PO2.
The O2 Dissociation Curve
Fig. 18-8 17-21
The O2 Dissociation Curve
plateau – prevents desaturation
even if PO2 falls
steep part – for loading
or unloading O2
The shape of the curve is affected by (Fig. 18-9, 18-10 1722, 17-23)
• CO2 (the Haldane effect),
• H+ (the Bohr effect),
• temperature, and
• 2,3-diphosphoglycerate (Fig. 18-10, 17-23).
Increases in H+, CO2 and temperature (as occurs in
exercising muscle; an increase in 2,3-DPG occurs when
the organism is hypoxemic (= low PaO2)) shifts the curve
to the right -- that is, decreases the affinity of Hb for O2 at
a given PO2 -- by changing the conformation of Hb so that
it binds less well to O2. This helps unload O2 to the
tissue.
Effect of CO2 (Haldane effect)
The rightward
shift of the O2
dissociation
curve due to
increases in
PCO2 is called
the Haldane
effect.
Fig. 18-9c 17-22c
In other words,
Hb can hold less
O2 in the
presence of a
high CO2. This is
good because it
helps O2
unloading to cells
of metabolically
active tissues.
Effect of pH (or [H+]) (Bohr effect)
Fig. 18-9a 17-22a
Effect of Temperature
Fig. 18-9b 17-22b
200
100
0
O2 Concentration (mL O2 / litre blood)
The O2 Dissociation Curve
The O2 Dissociation Curve in Anemia
normal
anemia
Despite a
reduced O2
carrying
capacity (for
whatever
reason), the
O2 dissociation
curve (when
the Y axis is
expressed as
percent O2
saturation of
Hb) is
unaffected.
200
100
0
O2 Concentration (mL O2 / litre blood)
The O2 Dissociation Curve in Anemia (2)
When the O2
dissociation
curve is
expressed as
O2 content, the
curve shifts
down (in this
case, by 50%
since the Hb
concentration is
reduced by half.
Dynamics of Diffusion of Gases at the
Alveolar-Pulmonary Capillary Interface
100
PcO2 (mmHg)
End-capillary
(pulmonary vein)
(arterialized)
50
mixed venous
(pulmonary artery)
0
0
0.5
Time (s)
end-capillary
1.0
PcO2 (mmHg)
100
Altitude ( PB)
50
0
0
0.5
Time (s)
end-capillary
1.0
PcO2 (mmHg)
100
Altitude ( PB)
50
PvO2
0
0
ΔPO2
0.5
Time (s)
end-capillary
1.0
PcO2 (mmHg)
100
cardiac output
faster
flow in pulmonary capillaries
less time for diffusion
50
0
Altitude ( PB)
desaturation
0
end-capillary
(exercise)
0.5
Time (s)
end-capillary
(rest)
1.0
CARBON DIOXIDE
p. 584-6, 527-9, 504-6
CO2 is relatively soluble in water/plasma/blood. Thus ~7%
(as opposed to O2's 0.3%, i.e., ~ 20 times as much,
reflecting CO2’s 20 x solubility) of CO2 is transported as
CO2 dissolved in plasma and red blood cells.
(Note: The percentages in which CO2 is carried in blood differ
according to who you read; I have used the values given in Silverthorn.
The values also depend on the site of sampling, arterial or venous).
About 23% of CO2 chemically combines with Hb as
carbaminohaemoglobin (HbCO2). Loss of O2 from Hb
increases Hb's affinity for CO2.
Most (~70%) CO2 is carried as bicarbonate (HCO3-), the
formation of which is depicted in Figure 18-13, 17-26. Note
that the HCO3- originates from the breakdown of carbonic
acid (H2CO3); as HCO3- builds up within the red blood
cell, it diffuses down its concentration gradient into the
plasma. To preserve electrical neutrality within the red
blood cell, Cl- diffuses in.
H+ produced by the dissociation of H2CO3 is buffered by
Hb (p. 586, 528, 506); thus, reduced Hb (Hb minus its O2)
helps prevent increases in acidity within the red blood cell
and the plasma.
In the lung, all these reactions reverse, resulting in the
formation of CO2, which then diffuses into the alveoli for
exhalation.
CO2 Transport
CO2 + H2O
H2CO3
carbonic anhydrase
Fig. 18-13, 17-26
H+ + HCO3-
Thus, CO2 produced by cells is carried by the blood in
three forms
dissolved CO2 (~7%)
carbaminohaemoglobin, HbCO2 (~23%), and
HCO3- (~70%)
to the lung where it is excreted as CO2 gas. If it were
not, we would rapidly become acidotic, enzymatic
reactions would stop, and we would die.
Control of Ventilation
p. 587-92, 529-35, 506-13
Objectives : see page R23
(see Fig. 18-19, 17-32, 18-18 17-31; 20-19 19-19 for
respiratory acidosis)
All control systems include:
• sensors (to monitor controlled variables)
• controller(s), and
• effector(s).
Fig. 18-15 17-28
Sensors: monitor the levels of O2, H+, and, especially,
CO2 in the blood (or tissues) with special cells called
chemoreceptors. They signal the
Controller(s) neurons in the respiratory control centres in
the brainstem, which then signal the
Effectors, respiratory pump (inspiratory and expiratory)
muscles or airway smooth muscle
Receptors:
PCO2, PO2, and H+ are sensed by the:
• peripheral (carotid and aortic; p. 589-91, 532-3,
510-1; Fig. 18-17, 17-30, 17-29) and
• central chemoreceptors.
Different receptors are not equally sensitive to CO2,
O2 and H+.
(Aortic chemoreceptors respond to O2 content and
primarily affect cardiac output and vascular resistance
(not stated in Silverthorn). They will not be described
further.)
Fig. 18-19
17-32
CARBON DIOXIDE
p. 589-91, 532-4, 509-12
Most important factor controlling ventilation.
.
VA is proportional to PaCO2
.
Self-limiting:
. if, at constant CO2 production (VCO2), you double
VA, you halve the PaCO2 (Fig. 17-15, 17-16). The drop in
PaCO2 reduces respiratory drive, and ventilation falls.
.
.
Recall that hyperventilating (increasing VA more than VCO2)
increases breathhold time; it works because you 'blow off' the
CO2 in your blood. (Hyper- or hypoventilation does not affect
O2 content so much because of the shape of the O2
dissociation curve.)
Central chemoreceptors, close to brainstem respiratory
neurons and the cerebrospinal fluid, are responsible for ~65%
of the ventilatory response to CO2.
Alveolar Ventilation and
Arterial Blood Gases
PaO2 or PaCO2 (mmHg)
‘normal’
.VA (L/min)
Fig. 17-15 17-16
Alveolar Ventilation and
Arterial Blood Gases
PaO2 or PaCO2 (mmHg)
‘normal’
Note:
.
2 x VA
Doubling VA
halves PaCO2
but does not
double PaO2.
Why?
.VA (L/min)
.
Standard Story
(See textbook p. 590, 533, 511-2, Figs. 18-17, 17-30 and 1818 17-31; even better p. 647-8, 591-2, 566-7).
Increased CO2 increases [H+] which stimulates the
central chemoreceptors. (This is a hypothesis, not fact.)
Brain [H+] does reflect CO2 levels (law of mass action, p.
590, 533, 511 and 647-8, 591-2, 565).
Peripheral (carotid) chemoreceptors are activated by
increases in PCO2. Their increased input to the respiratory
centres contributes to the increase in ventilation. But at
least 65% of the ventilatory response to CO2 remains
after cutting their afferents.
Fig. 18-18, 17-31
Oxygen
p. 589, 532, 510
Decreases in PaO2 are monitored ONLY by the carotid body
chemoreceptors; increased afferent activity stimulates the
brainstem respiratory centres and, therefore, ventilation.
Threshold: chemoreceptors are not activated until PaO2 falls
to ~65 mmHg. Why? Above this threshold, their activation
would be ineffective at increasing arterial O2 content because
Hb is already > 90% saturated at a PO2 of ~65-70 mmHg.
Hypoxia does not stimulate central chemoreceptors; in fact,
hypoxia depresses (often after a transient excitation) neurons
of the central nervous system. Thus, the ventilatory response
to hypoxia requires the carotid chemoreceptors.
H+
pp. 689-91, 532-4, 511-2 and 647-53, 590-7, 563-7
Peripheral chemoreceptors also respond to changes in
[H+] independent of changes in PCO2 (e.g., metabolic
acidosis in a diabetic). The increase in ventilation
represents a respiratory compensation for a metabolic
problem.
Use of the lungs to excrete CO2 has a major advantage: it
is fast (the response occurs in minutes versus hours or
days using the kidneys).
This important topic is covered in Ch. 20, 19, especially
pp. 647-53, 590-7, 563-571).
The Central Controller
p. 587-9, 530-2, 506-9
Breathing requires neurons in the brainstem (unlike the
heart beat which originates in specialized pacemaker cells
of the heart; the heart rate can be modified, but not
initiated, by cells in the brainstem).
Pacemaker cells may be important in newborn mammals,
but there appears to be a rapid switch to a respiratory
"network" (i.e., based on connections between
populations of cells).
How respiratory rhythm originates and is maintained is
still incompletely understood.
Negative Feedback
The Breuer-Hering Reflexes
p. 592, 535, 512-3
The first example of biological feedback.
Lung inflation prematurely terminated inspiration and delayed
the onset of the next inspiration. In contrast, prevention of
inspiration prolonged the duration of the inspiratory effort and
delayed the onset of the next expiration.
Thus, lung inflation reflexly results in its termination, a
process Breuer and Hering referred to as "selbst-steurung"
(or self-steering; the term "feedback" did not exist).
The reflex is present in most anesthetized animals and
newborn animals, but is weak, absent, or too subtle to detect
in non-anesthetized animals, especially adults.
Central Controller
brainstem
respiratory centers
+
+
respiratory and upper
airway muscles; airway
smooth muscle
+
chemoreceptors
and
mechanoreceptors
lung (passive)
Effectors
Sensors
Breuer-Hering
reflex
Central Controller
brainstem
respiratory centers
Descending nerves
(bulbo-spinal axons in
spinal cord)
+
phrenic motoneurons
diaphragm
Effectors
+
+
Vagus nerve
lung
Mechanoreceptors
(pulmonary slowly adapting
receptors)
Sensors
Cells Types of the Alveoli
• Type I alveolar cells
– simple squamous cells where gas exchange occurs
• Type II alveolar cells (septal cells)
– free surface has microvilli
– secrete alveolar fluid containing surfactant