UNIT 6: GAS EXCHANGE AND TRANSPORT

BIOL2420 D01 Lecture Notes

 A) Gas Exchange and Transport – Overview
Ø Body needs to bring oxygen (O2) into the blood and transport it to the
tissues for cellular respiration (i.e. to make ATP). Hypoxia = too little
oxygen.
Ø Body needs to eliminate CO2 (produced as a byproduct of cellular
respiration in the tissues), by transporting it in the blood to the the
lungs . Hypercapnia = too much CO2.
ØTo accomplish these tasks:
1. Oxygen diffuses out of alveoli across the respiratory membrane into blood
plasma (down its pressure gradient)
2. Oxygen is transported in blood dissolved in the plasma and bound to hemoglobin.
3. In capillary beds in the tissues, oxygen diffuses across capillary walls into interstitial
fluid (ISF) and then into the cells of the tissue (down its pressure gradient)
4. CO2 diffuses out of the cells in the tissue into ISF and then into blood plasma. Figure 18.2
5. CO2 is transported dissolved in blood plasma, bound to hemoglobin and as
bicarbonate ions (HCO3-)in the plasma.
6. CO2 diffuses into alveoli across the respiratory membrane.
B) Factors Affecting Gas Exchange

Figure 18.3
 B) Factors Affecting Gas Exchange
Ø At alveoli:
1. Composition of inspired air
See Figure 18.2
ØRecall – partial pressures of gasses determined by
percentage of gas in a mixture of gases:
• E.g. O2 at sea level = 20.95% of atmospheric air, so
partial pressure of O2 is = 20.95% x 760 mmHg (air
pressure at sea level) = 159.2 mmHg (~160mmHg)
Ø Partial pressure gradients for each gas promote their
movement (diffusion) from alveoli to blood and blood to
cells and vice versa..
Ø Composition of inspired air changes with altitude.
Oxygen still makes up 20.95% of air, but air pressure at
high altitude is lower (e.g. on Mount Everest is 247
mmHg, so PO2 = 51.7 mmHg). Increasing altitude causes
the pressure gradient between alveoli and blood plasma
to decrease (less steep of a gradient) so overall less
oxygen can enter the blood.
 B) Factors Affecting Gas Exchange
Ø At alveoli:
2. Alveolar ventilation
ØIn the alveoli, PO2 is lower and PCO2 is higher than in atmospheric air because of:
a. the humidification of the air as it passes through the upper respiratory
tract. This increases the PH2O (pressure of water vapour) in the air which reduces
the PO2.
b. the mixing of the fresh inspired air (PO2 = 160 mmHg, PCO2 = 0.25 mmHg)
with the stale air (lower PO2, higher PCO2) in the anatomic dead space and
alveoli to produce a PO2 of 100 mmHg and PCO2 of 40 mmHg in the alveoli.
ØLow alveolar ventilation (hypoventilation) results in accumulation of stale low
PO2, high PCO2 air in the alveoli, which will decrease the pressure gradient
for gas exchange across the respiratory membrane.
• Low alveolar ventilation (hypoventilation) can be caused by:
a. decreased lung compliance
b. increased airway resistance (e.g. asthma)
c. decreased Central Nervous System activity that results in decreased breathing Figure 18.2
(ventilation) rate and depth (e.g. occurs in alcohol poisoning, drug overdose).
 B) Factors Affecting Gas Exchange
Ø At alveoli:
3. Factors affecting diffusion of gases: Diffusion ~ (surface area x concentration
gradient x permeability)/distance2
a. Concentration (Pressure) gradient of gasses - in healthy lungs = primary factor
affecting gas exchange.
Ø The steeper the gradient the more gas diffusion will occur
Ø Gradient is affected by composition of air and alveolar ventilation (see previous
slides).
Ø Concentration of oxygen in air and in solution()plasma) is measured in mmol O2/L.
Concentration depends on solubility of the gas in the fluid of the plasma. O2 has
low solubility in water, and so its concentration in blood plasma leaving the lungs is
lower than in alveolar air, even though they both have the same partial pressure.
b. Surface area for exchange
Ø Greater alveolar surface area allows for more exchange of gasses.
Ø Emphysema decreases alveolar surface area, and therefore decreases gas
diffusion, resulting in poorly oxygenated blood.
Figure 18.3c
 B) Factors Affecting Gas Exchange
Ø At alveoli:
3. Factors affecting diffusion of gases: Diffusion ~ (surface area x concentration
gradient x permeability)/distance2
c. Diffusion barrier permeability
Ø Greater permeability allows for more exchange of gasses.
Ø Fibrotic lung diseases decrease permeability of the respiratory membrane, and
therefore decreases gas diffusion, resulting in poorly oxygenated blood.
d. Diffusion distance
Ø Normally diffusion distance is small (equivalent to the thickness of the
respiratory membrane (0.2 – 0.5 µm thick), which facilitates gas exchange.
Ø Pulmonary edema results in the accumulation of fluid in the alveoli which
increases the diffusion distance and therefore decreases gas diffusion, resulting
in poorly oxygenated blood.

Figure 18.3c
C) Oxygen Transport See Figure 18.2 & 18.5

Ø Oxygen is transported in 2 ways:

AT LUNGS
1. Dissolved in plasma (1.5%) – this is the PO2 of the blood
a. At lung capillaries:
Ø Oxygen diffuses down its pressure gradient from high pressure
(105 mmHg) in the alveolus to low pressure (40 mmHg) in the
capillary until equilibrium is almost reached.
Ø PO2 in the pulmonary vein =100 mmHg, so PO2 does not quite reach
equilibrium. This is due to the poor solubility of O2 in water – there is not
enough time for the gas to reach true equilibrium before blood leaves
the alveolar capillaries).
b. At tissue capillaries:

AT TISSUES
Ø Arterial PO2 = 100 mmHg
Ø Resting venous PO2 and ISF (interstitial fluid) PO2 = 40 mmHg
Ø Intracellular (ICF) PO2 = < 40 mmHg (since the cell is constantly
using oxygen for cellular respiration – ATP production).
Ø So at the tissue capillaries, oxygen diffuses down its pressure
gradient out of the arteriolar end of the capillary where PO2 is highest,
then into the ISF and then into the cell (down its partial pressure gradient)
C) Oxygen Transport
Ø Oxygen is transported in 2 ways:

Figure 18.4
2. Bound to Hemoglobin (98.5%)
a. Problem: Oxygen exhibits low solubility in aqueous solutions, as a result,
very little can be carried in the plasma (only ~0.3 mL O2 dissolved per
100 mL of plasma). In contrast CO2 solubility is 20X higher. For a given
partial pressure, more CO2 will dissolve in water than O2.
b. Solution: Hemoglobin (Hb)
Ø Found only in erythrocytes (RBCs)
Ø Allows more oxygen to be transported in the blood
Ø Adult Hb (HbA) is compsed of two a-globin and two b-globin chains,
each of which is bound to an iron (Fe2+) containing heme group.
Ø Oxygen binds reversibly to Fe2+

Figure 18.5
Ø Fe2+ binds oxygen when plasma PO2 is high (in pulmonary
capillaries)
Ø Fe2+ releases oxygen when PO2 is low (in systemic capillaries).
Ø NOTE: Myoglobin (Mb) is a similar molecule that facilitates O2
delivery within skeletal and cardiac muscle.
C) Oxygen Transport
Ø Oxygen is transported in 2 ways:

Figure 18.4
2. Bound to Hemoglobin (98.5%)
a. Problem: Oxygen exhibits low solubility in aqueous solutions, as a result,
very little can be carried in the plasma (only ~0.3 mL O2 dissolved per 100
mL of plasma). In contrast CO2 solubility is 20X higher. For a given partial
pressure, more CO2 will dissolve in water than O2.
b. Solution: Hemoglobin (Hb)
Ø Found only in erythrocytes (RBCs)
Ø Allows more oxygen to be transported in the blood
Ø Adult Hb (HbA) is composed of two a-globin and two b-globin chains,
each of which is bound to an iron (Fe2+) containing heme group.
Ø Oxygen binds reversibly to Fe2+

Figure 18.5
Ø Fe2+ binds oxygen when plasma PO2 is high (in pulmonary
capillaries)
Ø Fe2+ releases oxygen when PO2 is low (in systemic capillaries).
Ø NOTE: Myoglobin (Mb) is a similar molecule that facilitates O2 delivery
within skeletal and cardiac muscle.
C) Oxygen Transport
Ø Note: Once O2 binds to Hb (or myoglobin, Mb) it no longer contributes to the PO2 of the plasma
Ø As a result, PO2 is entirely determined by the amount of O2 that is dissolved in the plasma
Ø Loading and unloading of O2 onto hemoglobin obeys the law of mass action:
Ø Increasing the concentration of one substance involved in a reversible reaction drives that reaction
towards the opposite direction PO ® PO + Hb ↔ Hb–O
2 2 2
alveoli plasma DeoxyHb OxyHb
Ø Because alveolar PO2 > plasma PO2, oxygen continually diffuses into the blood plasma in the
pulmonary capillaries and then it quickly binds to Hb, which removes it from the plasma. This keeps
PO2 low, so that the gradient is maintained until the Hb molecules become saturated. Hb is never
100% saturated, only ~98%, since some hemoglobin molecules are defective and cannot bind to O).
Ø As a result binding of oxygen to Hb depends on 2 things: 1) PO2 of the plasma, and 2) the number of
binding sites for O2 on hemoglobin. PO ← PO + Hb ↔ Hb–O
2 2 2
Ø At the tissues, the reaction is reversed and Hb transfers O2 ISF plasma DeoxyHb OxyHb
to the plasma, then across the wall of the capillary into the ISF and then into the cell.
Ø Hb (and Mb) act as “storage depots” that promote the rapid transfer of O2 to and from the plasma.
D) O2-Hb Saturation Curves

Figure 18.9
Ø Amount of O2 bound to Hb at any given PO2 is the percent
saturation of hemoglobin
Ø = amount of O2 bound ÷ amount that could be bound × 100
Ø The relationship is shown on an O2-Hb Saturation Curve
Ø Curve is sigmoidal due to cooperative oxygen binding
between Hb and O2. When oxygen binds to one site on the
Hb tetramer, a conformational change occurs that increases
the oxygen binding affinity at the other sites (and vice
versa). So Hb releases/takes up O2 quickly through the Binding affinity of Hb for 4th O2
middle portions of the graph resulting a steep section is ~300× higher than for 1st O2
(where O2 is gained/lost easily). But in the plateau where
Hb is saturated even large changes in PO2 have no impact
on saturation (more difficult to gain/lose oxygen).
Ø High PO2 levels increase affinity of Hb for oxygen
(promote O2 loading), low PO2 levels decrease affinity
(promote O2 offloading).
D) O2-Hb Saturation Curves
Hemoglobin
plateau
100 •

Ø Significance of the O2-Hb Saturation Curve:

Oxygen

Percent O2 saturation of hemoglobin

80 If more O2 is
a. Upper Plateau Portion present,
more O2 is
Ø ~ between 60 mmHg and 100mmHg PO2

ep
60 bound.

st e
Ø Spans the PO2 range typically found in the alveoli/
pulmonary capillaries at which Hb picks up O2, thereby 40

ensuring that Hb is >90% saturated over a wide

range of PO2 values. If alveolar PO2 decreases a little 20

below normal, there is little change in Hb saturation.

Ø Allows for changes in lung function, altitude/elevation
•
0
0 20 40 60 80 100

with minimal impact on hemoglobin saturation. PO2 (mm Hg)

Marieb and Hoehn 2018.
Sea Level vs. 3000 m elevation
Alveolar PO2 = 100 mmHg Alveolar PO2 = 70 mmHg e.g. Mount Everest south base camp is
Hb = ~98% saturated Hb = 92% saturated at 5364 m and the peak is 8849 m.
(~20 mL O2/100 mL blood). (~19 mL O2/100 mL blood). Arterial PO2 of climbers can be as low
as 19.0 mmHg, representing a
Ø However, O2 loading becomes problematic when alveoli drop hemoglobin saturation of ~20%.
Further reading:
below 70 mmHg, as occurs in fibrotic and obstructive lung
https://www.nejm.org/doi/pdf/10.1056/
diseases or changes in altitude to elevations greater than 3000 m NEJMoa0801581
D) O2-Hb Saturation Curves
Hemoglobin
plateau
100 •

Ø Significance of the O2-Hb Saturation Curve:

Oxygen

Percent O2 saturation of hemoglobin

80 If more O2 is
b. Steep Portion present,
more O2 is
Ø ~ between 10 mmHg and 50 mmHg PO2

ep
60 bound.

st e
Ø Spans the PO2 range typically found in the plasma at the
systemic capillaries (PO2 of ISF of tissues). 40

Ø At rest, venous blood is still largely saturated (i.e.

deoxygenated blood is not actually fully deoxygenated, 20

only ~23% is offloaded to tissues at rest, leaving Hb

~75% saturated at the tissues.)
•
0

vs.
0 20 40 60 80 100

Sea Level Exercise PO2 (mm Hg)

capillary PO2 = 40 mmHg capillary PO2 = 20 mmHg Marieb and Hoehn 2018.
Hb = ~75% saturated Hb = 30% saturated
(~15 mL O2/100 mL blood). (~6 mL O2/100 mL blood).
Ø Relatively small drops in plasma PO2 that occur in active
tissues during exercise cause the Hb to automatically
release much more O2 to these structures. (98% - 30% =
68% offloaded to exercising tissues)
D) O2-Hb Saturation Curves
Ø Half Saturation oxygen pressure P50
Ø The affinity of Hb (or blood) for O2 is often expressed as its P50
Ø = plasma PO2 at which 50% of the Hb molecules are saturated
with oxygen (i.e. 50% of Hb are in the form of DeoxyHb and
50% are in the form of OxyHb).

% Hb-O2 Saturation 100

75
↑ P50 = ↓ Hb-O2 affinity
(shifts curve to right)
50

25
↓ P50 = ↑ Hb-O2 affinity
(shifts curve to left)
0
22 27 32
Plasma PO2
(mm Hg)
 D) O2-Hb Saturation Curves
Ø Factors causing shifts to RIGHT in the O2-Hb Saturation Curve (↑ P50 )
Ø For a given PO2, get less Hb saturation (i.e. O2 offloads more easily and
loads less easily under these conditions)
Ø Occurs when:
1. ↓ pH (↑ H+)
Ø Tissue O2 delivery is augmented by metabolic acidification of blood cells in
the tissue capillaries by CO2 and lactic acid (Bohr effect)
Ø E.g. CO2 + H2O↔H2CO3↔HCO3- + H+
Figure 18.9
Ø Hb can reversibly bind to H+, which stabilizes the Deoxy form of Hb,
muscle capillary
promoting release of oxygen. pH during
exercise
arterial

Log P50
pH

systemic
capillary pH
at rest

7.0 7.4 7.8

pH
 D) O2-Hb Saturation Curves
Ø Factors causing shifts to RIGHT in the O2-Hb Saturation Curve (↑ P50 )
Ø For a given PO2, get less Hb saturation (i.e. O2 offloads more easily and
loads less easily under these conditions)
Ø Occurs when:
2. ↑ PCO2
Ø Can bind reversibly to amnio group of each a- and b-chain, forming a
carbamino (NHCO2-) protein
Ø Stabilizes the Deoxy form of Hb, promoting release of oxygen.
Ø H+ ions release from binding of CO2 to NH2 can bind elsewhere on the Hb
molecule which contributes to the Bohr effect.
Ø However CO2 competes for one the 2,3 DPG binding sites, so carbamino
formation is inhibited when DPG is produced (and at low pH).
Ø As a result only ~5% of all CO2 in veins is transported bound directly to Figure 18.9
Hb
 D) O2-Hb Saturation Curves
Ø Factors causing shifts to RIGHT in the O2-Hb Saturation Curve (↑ P50 )
Ø For a given PO2, get less Hb saturation (i.e. O2 offloads more easily and
loads less easily under these conditions)
Ø Occurs when:
3. ↑ 2,3-diphosphoglycerate (DPG)
Ø Polyanionic side-product of glycolysis in RBCs
Ø 2,3-DPG can bind to Hb which stabilizes the Deoxy form of Hb, promoting
release of oxygen.
Figure 18.9
Ø DPG is only found inside RBCs, and is the primary allosteric effector
T-state Hb
responsible for increasing the P50 of ‘pure’ Hb (~5 mmHg) to that of whole α
β β143
blood (~26 to 28 mmHg) β2

β82
Ø DPG production by RBCs increases when arterial blood is chronically β1
under-saturated (e.g. anemia, pulmonary disease) β82
β1

Ø increases whole blood P50 above 28 mm Hg, allowing more O2 to be extracted. β2

from Hb at the systemic capillaries with relatively little effect on O2 uptake in the. α β143
β
lungs
 D) O2-Hb Saturation Curves
Ø Factors causing shifts to RIGHT in the O2-Hb Saturation Curve (↑ P50 )
Ø For a given PO2, get less Hb saturation (i.e. O2 offloads more easily and
loads less easily under these conditions)
Ø Occurs when:
4. ↑ Temperature
Ø Deoxygenation of Hb is an endothermic reaction (i.e. it requires free energy
in the form of heat)
Ø Increasing temperature increases the amount of free energy available, which
lowers the affinity of Hb for O2.
Figure 18.9
Ø Note: increasing temperature also decreases pH (increases H+) which
would further promote oxygen offloading (an increase in P50) 30

P50 (mm Hg)

28

26
36 38 40
Temperature (°C)
 D) O2-Hb Saturation Curves
Ø Factors causing shifts to LEFT in the O2-Hb Saturation Curve (↓P50 )
Ø For a given PO2, get more Hb saturation (i.e. O2 offloads
less easily and loads more easily under these conditions)
Ø Representative of conditions at the lungs
Ø Occurs when:
1. ↑ pH (↓ H+)
2. ↓ PCO2
3. ↓ 2,3-diphosphoglycerate (DPG)
4. ↓ Temperature

Figure 18.9
 E) Maternal/Fetal O2 Transport
Ø O2 transport from maternal to fetal circulation is
facilitated by expression of a different Hb isoform
in the fetus (fetal Hb, or HbF)
Ø Fetal hemoglobin has (gamma) g-globin chains
instead of the beta-globin chains seen in HbA.
Ø This change decreases the number of bonds that DPG
can form with Hb, which decreases fetal blood P50 to ~
21 mmHg which is lower than that of maternal blood
(~28 mmHg).
Ø The lower P50 acts as a shift to the left in the placenta,
and so promotes the transfer of oxygen from the HbA
of the mother’s blood to the HbF of the fetus. Oxygen
loading of HbF increases (offloading decreases), and
so we observe a higher saturation of fetal blood with Figure 18.9b
oxygen for the same PO2.
F) Total Arterial O2 Content

Figure 17.2
 F) Total Arterial O2 Content
Ø Example of regulating O2 delivery: During Exercise:
1. Cardiovascular adjustments
a. Increased cardiac output à increased blood flow to lungs and working
tissues (increased perfusion)
b. Autoregulation – increased blood flow to exercising muscles
2. Ventilation adjustments
a. Increased respiratory rate and depth increases alveolar ventilation.
3. Hemoglobin (local effects at capillaries of exercising muscles promote offloading of O2)
a. Increased temperature (muscle contraction produces heat) decreases affinity of hemoglobin
for oxygen
b. Increased PCO2 and {H+} cause a decrease in blood pH (increased Bohr effect) (lowers affinity)
c. Decreased pH increases DPG binding (lowers affinity, promotes offloading)
Ø All of the above (2a, b, c) shift the O2-Hb dissociation curve to the right, causing O2 to be
offloaded from Hb at higher PO2. thereby increasing the PO2 pressure gradient between the
blood plasma and the mitochondria in the cells of the tissue. A steeper gradient means more
O2 will be delivered to the cells.
 G) Carbon Dioxide Transport
Ø Carbon dioxide (CO2) is transported in 4 ways:
1. Dissolved in the plasma (~5%, but up to 15% during strenuous exercise).
Ø This is the PCO2 of the blood, other forms of CO2 transport do not TEXTBOOK CORRECTION:
contribute to the PCO2 of the blood Percentages for CO2 transport
in the textbook are old values.
2. Bound to amino groups of plasma proteins (<1%). The values given here reflect
3. Bound to amino groups of hemoglobin in red blood cells, forming current understanding are what
you need to know for
carbaminohemoglobin (~5%).
quizzes/exams.
4. As bicarbonate ions (HCO3-) in the blood plasma (~90% total)
Ø Some produced in plasma itself (~5%)
Ø Most produced inside of red blood cells and moved to the plasma (~85%).
G) Carbon Dioxide Transport
Modified from
Figure 18.11
NOTE: this image
has been edited for
both accuracy and
content and so is
not exactly the
same as the
textbook version.
On any quiz or
exam – this edited
figure represents
the information you
would be tested on
(particularly the
percentages of
CO2 being carried
in different ways)
 G) Carbon Dioxide Transport
Ø Carbon dioxide (CO2) is transported in 4 ways:
1. Dissolved in the plasma (~5%, but up to 15% during strenuous exercise).
Ø CO2 is 25 times more soluble in aqueous solutions than O2, so more of it can be
carried dissolved directly in the plasma.
a. At systemic tissue capillaries:
Ø Arterial PCO2 = 40 mmHg
Ø Intracellular Fluid PCO2 = >46 mmHg
Ø Interstitial Flujd PCO2 = 46 mmHg
Ø Resting Venous PCO2 = 46 mmHg
Ø As blood enters the tissue capillaries (at PCO2 = 40 mmHg) carbon dioxide
diffuses down its pressure gradient from high pressure (>46 mmHg) in the
tissue cells to the ISF (46 mmHg) and then into the capillary until equilibrium
is reached.
b. At pulmonary (lung) capillaries:
Ø CO2 diffuses down its pressure gradient from high pressure (46 mmHg) in the
arterial capillary to low pressure (40 mmHg) in the alveoli. At the same time,
oxygen is diffusing down its pressure gradient in the opposite direction.
 G) Carbon Dioxide Transport
Ø Carbon dioxide (CO2) is transported in 4 ways:
2. Bound to amino groups of plasma proteins (<1%).
Ø CO2 + protein-NH2 ↔ protein-NHCOO- + H+
3. Bound to amino groups on globin portion of hemoglobin =
carbaminohemoglobin (~5%).
4. As bicarbonate ions (HCO3-) in the blood plasma (~90% total)
Ø HCO3- can accumulate to very high concentrations, allowing
the transport of a lot of CO2
Ø Conversion of CO2 into HCO3- at the systemic tissue
capillaries (and back to CO2 in the pulmonary capillaries of
the lungs) is catalyzed in RBCs by the enzyme carbonic
anhydrase (CA) – but some CA is also found on the Modified from Figure 18.11
endothelium of the capillaries in both locations.
Ø Reaction follows the law of mass action (build up of
substrates/products will push the equation in one direction or
the other)
G) Carbon Dioxide Transport
4. As bicarbonate ions (HCO3-) in the blood plasma
(~90% total)
Ø Process:
a. Inside RBC at systemic capillaries (i.e. at capillaries of
organs other than respiratory zone of lungs, where
cellular respiration ↑ CO2)
CA
Ø CO2 + H2O ® H2CO3 ® H+ + HCO3-
Ø H+ + Hb ® HbH (Hb is a buffer)
Ø HCO3- formed in RBC is transported out of RBC via
the Band 3 antiport protein in exchange for Cl-. This
process, known as the chloride shift allows for:
i. Production of more HCO3- by keeping [HCO3-] in
the RBC low and overall increased transport of
CO2
ii. Minimization of pH changes in venous blood Modified from Figure 18.11
(HCO3- as a buffer)
iii. Maintenance of electrical neutrality of RBCs
G) Carbon Dioxide Transport
4. As bicarbonate ions (HCO3-) in the blood plasma
(~90% total)
Ø Process:
b. Inside RBC at pulmonary capillaries (i.e. at capillaries in
respiratory zone of lungs, where CO2 level are low)
Ø O2 + deoxyHb ® HbO2 (note: deoxyHb can be HbH
or HbCO2)
Ø Low PCO2 in the alveoli, moves dissolved CO2 out of
the blood plasma, which promotes the reverse
reaction:
CA
Ø H+ + HCO3- ® H2CO3 ® CO2 + H2O
Ø As CO2 moves out of the RBC mass action results in
reverse chloride shift (HCO3- moves into cell in
exchange for Cl- and is converted by CA into CO2
and H2O. CO2 moves out of the cell down its
pressure gradient into plasma and then across the
respiratory membrane into the alveoli so that it can
Modified from Figure 18.11
be expired).
 60

Minute ventilation (L/min)

G) Regulation of Respiration 40
Ø It is important to precisely regulate minute alveolar
ventilation in order to maintain normal arterial PO2 20 normal PO2

and PCO2 levels.

0
20 40 60 80 100 120 140
Ø Breathing rate and depth are under both voluntary Arteriolar PO2 (mm Hg)
and involuntary control of the skeletal muscles
responsible for respiration:
Ø Diaphragm and external intercostals for normal
“quiet” inspiration (i.e. breathing at rest)
Ø Sternocleidomastoid and scalenes are recruited
during forced inspiration (e.g. taking deep breaths,
such as during exercise).
Ø Quiet expiration occurs due to relaxation of
external intercostals and diaphragm.
Ø Forced (or deep expiration is assisted by
contraction of abdominal muscle and internal
intercostals. Figure 18.13
 G) Regulation of Respiration
1. Respiratory centres in the medulla
Ø Set the rate depth and rhythm of breathing.
Ø 2 main groups of neurons that form the central pattern generator
a. Ventral Respiratory Group (VRG)
Ø contains an area call the pre-Bötzinger complex which
generates the rhythmic rate of breathing (pacemaker)
Ø has both inspiratory and expiratory neurons Similar to Figure 18.14
b. Dorsal Respiratory Group (DRG)
Ø receives sensory information from stretch receptors in the
lungs, and central and peripheral chemoreceptors
Ø modulates basic rhythm by signalling changes to VRG
2. Pontine respiratory centres
Ø Work with medullary centers to make breathing smooth and even.
Ø Damage to pontine respiratory centres produces short gasping,
Similar to Figure 18.13
irregular breaths.
G) Regulation of Respiration
3. Voluntary Control
Ø Primary motor cortex in cerebrum signals to lower motor neurons
going to muscles of inspiration (bypasses medulla).
Ø If medulla is damaged – must remember to breathe
Ø Can voluntarily hold breath, but eventually PCO2 gets very high, is
detected by chemoreceptors, and the medulla will override your
voluntary control and force you to take a breath
4. Pulmonary stretch receptors
Ø In smooth muscle of bronchi and bronchioles. Figure 18.13
Ø Hering-Breuer Reflex:
receptors overstretched on inspiration
impulses via vagus nerve
inhibit inspiratory neurons

relaxes muscles (expiration - prevents over inflation of lungs)

G) Regulation of Respiration
5. Chemical control (chemoreceptors)
a. Peripheral chemoreceptors
Ø Glomus cells in the carotid and aortic bodies (similar location to the
baroreceptors monitoring blood pressure) are in direct contact with
arterial blood
Ø Strongly activated when plasma PO2 drops below 60 mmHg
(emergency situation)
Ø More often stimulated by increases in both arterial PCO2 and/or [H+]
Ø In response to ↑ PCO2/[H+] or ↓↓[O2] glomus cells release
neurotransmitters onto sensory neurons projecting to the medulla (to the
DRG), and stimulate an increased rate of ventilation.
Ø Activity of these cells is not affected by anemia or carbon monoxide
(CO) poisoning, since in both of these conditions, PO2 of the blood
remains at normal levels (keeping ventilation rate the same, even
though the amount of O2 bound to Hb is changed).
Ø In CO poisoning, Hb has a much greater affinity for CO than for O2. So
at the lungs, Hb binds preferentially to CO instead of O2 forming Figure 18.16
carboxyhemoglobin.
G) Regulation of Respiration
5. Chemical control (chemoreceptors)
b. Central chemoreceptors
Ø Located in the medulla , these neurons largely dictate the
respiratory pace at rest.
Ø Respond only to changes in the pH of the cerebrospinal
fluid (CSF) surrounding the medulla (this pH decreases
when there is an increase in PCO2).
Ø CO2 (but not H+ or HCO3-) readily crosses the blood
brain barrier where it is converted into H+ and HCO3-
in the CSF by carbonic anhydrase
Ø When stimulated by H+, these receptors signal the
medulla to increase the rate and depth of ventilation. Figure 18.17
Faster, deeper breathing, will help to decrease PCO2
and increase PO2, to normal levels in the blood plasma.
Ø If PCO2 is chronically elevated, there will be increased
active transport of HCO3- from plasma into the medullary
CSF. This will buffer excess H+ and decrease
chemoreceptor firing (adaptation of the receptor).
 G) Regulation of Respiration
Ø Summary of central and Arterial PO2 ↓↓ (<60 mmHg) Arterial PCO2 ↑
peripheral
chemoreception and their
impact on ventilation Arterial Medulla ISF PCO2 ↑
[H+] ↑ (pH ↓)
*this pathway overrides voluntary carbonic anhydrase
control and is the most powerful ↑ Medulla CSF [H+]
detected
pathway regulating ventilation. by detected by
detected by
Ø For example, if you try to hold your
breath for as long as possible, PCO2
increases and is converted into H+ in Peripheral Central
the medulla. This triggers the central Chemoreceptors chemoreceptors
chemoreceptors, which signal to the (glomus cells)
medullary respiratory centres to
increase ventilation rate. Firing of Negative feedback will
*
Negative feedback will
inspiratory neurons will override the return PO2 levels to within ↑ Ventilation return PCO2 levels to
voluntary control from the cerebral set point range. within set point range.
cortex and you will be forced to take a
breath.
 H) Useful Video Links
1. Oxygen transport and oxygen-hemoglobin
dissociation curves
https://www.youtube.com/watch?v=BYGPkRFvzOc
Ø Note: in this video, the drawing suggests that
oxygen binds to the globin portion of
hemoglobin, which is incorrect. Oxygen binds to
the Fe2+ that is part of the heme.
2. Gas Exchange (CO2 Transport & Exchange)
https://www.youtube.com/watch?v=qDrV33rZlyA
Ø Note: in this video, the percentages of gases
transported by various mean is is not as precisely
reported as in your notes. Refer to the lecture
notes for correct percentages.).