UNIT 6: GAS EXCHANGE AND

TRANSPORT
BIOL2420 D01 Lecture Notes
 A) Gas Exchange and Transport – Overview
 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.
 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.
To 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
 At alveoli:
1. Composition of inspired air
See Figure 18.2
Recall – 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)
 Partial pressure gradients for each gas promote their
movement (diffusion) from alveoli to blood and blood to
cells and vice versa..
 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 PO = 51.7
2

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
 At alveoli:
2. Alveolar ventilation
 In 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.
 Low 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) Figure 18.2
c. decreased Central Nervous System activity that results in decreased breathing
B) Factors Affecting Gas Exchange
 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.
 The steeper the gradient the more gas diffusion will occur
 Gradient is affected by composition of air and alveolar ventilation (see previous
slides).
 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
 Greater alveolar surface area allows for more exchange of gasses.
 Emphysema decreases alveolar surface area, and therefore decreases gas diffusion,
resulting in poorly oxygenated blood.
Figure
B) Factors Affecting Gas Exchange
 At alveoli:
3. Factors affecting diffusion of gases: Diffusion ~ (surface area x concentration
gradient x permeability)/distance2
c. Diffusion barrier permeability
 Greater permeability allows for more exchange of gasses.
 Fibrotic lung diseases decrease permeability of the respiratory membrane, and
therefore decreases gas diffusion, resulting in poorly oxygenated blood.
d. Diffusion distance
 Normally diffusion distance is small (equivalent to the thickness of the respiratory
membrane (0.2 – 0.5 µm thick), which facilitates gas exchange.
 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
C) Oxygen Transport See Figure 18.2 & 18.5

AT LUNGS
 Oxygen is transported in 2 ways:
1. Dissolved in plasma (1.5%) – this is the PO2 of the blood
a. At lung capillaries:
 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.
 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
 Arterial PO2 = 100 mmHg
 Resting venous PO2 and ISF (interstitial fluid) PO2 = 40 mmHg
 Intracellular (ICF) PO2 = < 40 mmHg (since the cell is constantly
using oxygen for cellular respiration – ATP production).
 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
 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)
 Found only in erythrocytes (RBCs)
 Allows more oxygen to be transported in the blood
 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.
 Oxygen binds reversibly to Fe2+

Figure 18.5
 Fe2+ binds oxygen when plasma PO2 is high (in pulmonary
capillaries)
 Fe2+ releases oxygen when PO2 is low (in systemic capillaries).
 NOTE: Myoglobin (Mb) is a similar molecule that facilitates O2
delivery within skeletal and cardiac muscle.
C) Oxygen Transport
 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)
 Found only in erythrocytes (RBCs)
 Allows more oxygen to be transported in the blood
 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.
 Oxygen binds reversibly to Fe2+

Figure 18.5
 Fe2+ binds oxygen when plasma PO2 is high (in pulmonary capillaries)
 Fe2+ releases oxygen when PO2 is low (in systemic capillaries).
 NOTE: Myoglobin (Mb) is a similar molecule that facilitates O2 delivery
within skeletal and cardiac muscle.
 C) Oxygen Transport
 Note: Once O2 binds to Hb (or myoglobin, Mb) it no longer contributes to the PO2 of the plasma
 As a result, PO2 is entirely determined by the amount of O2 that is dissolved in the plasma
 Loading and unloading of O2 onto hemoglobin obeys the law of mass action:
 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
 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).
 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. PO2 PO2 + Hb Hb–O2
 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.
 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
 Amount of O2 bound to Hb at any given PO2 is the percent
saturation of hemoglobin
 = amount of O2 bound amount that could be bound 100

 The relationship is shown on an O2-Hb Saturation Curve

 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 Binding affinity of Hb for 4th O2
Hb releases/takes up O2 quickly through the middle portions is ~300× higher than for 1st O2
of the graph resulting a steep section (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).
 High PO2 levels increase affinity of Hb for oxygen
(promote O2 loading), low PO2 levels decrease affinity
D) O2-Hb Saturation Curves plateau
Hemoglobin

100 •

 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

ep
 ~ between 60 mmHg and 100mmHg PO2 60 bound.

ste
 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.

•
 Allows for changes in lung function, altitude/elevation with 0
0 20 40 60 80 100
PO (mm Hg)
minimal impact on hemoglobin saturation. 2

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
 However, O2 loading becomes problematic when alveoli drop hemoglobin saturation of ~20%. Further
reading:
below 70 mmHg, as occurs in fibrotic and obstructive lung diseases https://www.nejm.org/doi/pdf/10.1056/
or changes in altitude to elevations greater than 3000 m NEJMoa0801581
D) O2-Hb Saturation Curves plateau
Hemoglobin

100 •

 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

ep
 ~ between 10 mmHg and 50 mmHg PO2 60 bound.

ste
 Spans the PO2 range typically found in the plasma at the
systemic capillaries (PO2 of ISF of tissues). 40

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

20
deoxygenated blood is not actually fully deoxygenated,
only ~23% is offloaded to tissues at rest, leaving Hb ~75% •
0
saturated at the tissues.) 0 20 40 60 80 100

Sea Level vs. Exercise PO

capillary PO2 = 40 mmHg
Hb = ~75% saturated
(~15 mL O2/100 mL blood).
2 (mm Hg)
Marieb and Hoehn 2018.
capillary PO2 = 20 mmHg
Hb = 30% saturated
(~6 mL O2/100 mL blood).

 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
 Half Saturation oxygen pressure P50
 The affinity of Hb (or blood) for O2 is often expressed as its P 50
 = 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
 Factors causing shifts to RIGHT in the O2-Hb Saturation Curve (↑ P50 )
 For a given PO2, get less Hb saturation (i.e. O2 offloads more easily and
loads less easily under these conditions)
 Occurs when:
1. ↓ pH (↑ H+)
 Tissue O2 delivery is augmented by metabolic acidification of blood cells in
the tissue capillaries by CO2 and lactic acid (Bohr effect)
 E.g. CO2 + H2OH2CO3HCO3- + H+ Figure 18.9
 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
 Factors causing shifts to RIGHT in the O2-Hb Saturation Curve (↑ P50 )
 For a given PO2, get less Hb saturation (i.e. O2 offloads more easily and
loads less easily under these conditions)
 Occurs when:
2. ↑ PCO2
 Can bind reversibly to amnio group of each a- and -chain, forming a
carbamino (NHCO2-) protein
 Stabilizes the Deoxy form of Hb, promoting release of oxygen.
 H+ ions release from binding of CO2 to NH2 can bind elsewhere on the Hb
molecule which contributes to the Bohr effect.
 However CO2 competes for one the 2,3 DPG binding sites, so carbamino
formation is inhibited when DPG is produced (and at low pH). Figure 18.9
 As a result only ~5% of all CO2 in veins is transported bound directly to
Hb
 D) O2-Hb Saturation Curves
 Factors causing shifts to RIGHT in the O2-Hb Saturation Curve (↑ P50 )
 For a given PO2, get less Hb saturation (i.e. O2 offloads more easily and
loads less easily under these conditions)
 Occurs when:
3. ↑ 2,3-diphosphoglycerate (DPG)
 Polyanionic side-product of glycolysis in RBCs
 2,3-DPG can bind to Hb which stabilizes the Deoxy form of Hb, promoting
release of oxygen. Figure 18.9
 DPG is only found inside RBCs, and is the primary allosteric effector T-state Hb
β
responsible for increasing the P50 of ‘pure’ Hb (~5 mmHg) to that of whole α
β2
β143

blood (~26 to 28 mmHg) β82

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

β2
 increases whole blood P50 above 28 mm Hg, allowing more O2 to be extracted. from α β143
β
Hb at the systemic capillaries with relatively little effect on O 2 uptake in the. lungs
 D) O2-Hb Saturation Curves
 Factors causing shifts to RIGHT in the O2-Hb Saturation Curve (↑ P50 )
 For a given PO2, get less Hb saturation (i.e. O2 offloads more easily and
loads less easily under these conditions)
 Occurs when:
4. ↑ Temperature
 Deoxygenation of Hb is an endothermic reaction (i.e. it requires free energy in
the form of heat)
 Increasing temperature increases the amount of free energy available, which Figure 18.9
lowers the affinity of Hb for O2.
 Note: increasing temperature also decreases pH (increases H+) which would
further promote oxygen offloading (an increase in P 50) 30

P50 (mm Hg)

28

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

Figure 18.9
 E) Maternal/Fetal O2 Transport
 O2 transport from maternal to fetal circulation is
facilitated by expression of a different Hb isoform
in the fetus (fetal Hb, or HbF)
 Fetal hemoglobin has (gamma) g-globin chains
instead of the beta-globin chains seen in HbA.
 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).
 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
 Example of regulating O2 delivery: During Exercise:
1. Cardiovascular adjustments
a. Increased cardiac output  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 O 2)
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)
 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
 Carbon dioxide (CO2) is transported in 4 ways:
1. Dissolved in the plasma (~5%, but up to 15% during strenuous exercise).
TEXTBOOK CORRECTION:
 This is the PCO2 of the blood, other forms of CO2 transport do not contribute
Percentages for CO2 transport in
to the PCO2 of the blood the textbook are old values. The
2. Bound to amino groups of plasma proteins (<1%). values given here reflect current
understanding are what you need
3. Bound to amino groups of hemoglobin in red blood cells, forming to know for quizzes/exams.
carbaminohemoglobin (~5%).
4. As bicarbonate ions (HCO3-) in the blood plasma (~90% total)
 Some produced in plasma itself (~5%)
 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
 Carbon dioxide (CO2) is transported in 4 ways:
1. Dissolved in the plasma (~5%, but up to 15% during strenuous exercise).
 CO2 is 25 times more soluble in aqueous solutions than O 2, so more of it can be carried
dissolved directly in the plasma.
a. At systemic tissue capillaries:
 Arterial PCO2 = 40 mmHg
 Intracellular Fluid PCO2 = >46 mmHg
 Interstitial Flujd PCO2 = 46 mmHg
 Resting Venous PCO2 = 46 mmHg
 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:
 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,
 G) Carbon Dioxide Transport
 Carbon dioxide (CO2) is transported in 4 ways:
2. Bound to amino groups of plasma proteins (<1%).
 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)
 HCO3- can accumulate to very high concentrations, allowing the
transport of a lot of CO2
 Conversion of CO2 into HCO3- at the systemic tissue capillaries
(and back to CO2 in the pulmonary capillaries of the lungs) is Modified from Figure 18.11
catalyzed in RBCs by the enzyme carbonic anhydrase (CA) –
but some CA is also found on the endothelium of the capillaries
in both locations.
 Reaction follows the law of mass action (build up of
G) Carbon Dioxide Transport
4. As bicarbonate ions (HCO3-) in the blood plasma
(~90% total)
 Process:
a. Inside RBC at systemic capillaries (i.e. at capillaries of
organs other than respiratory zone of lungs, where cellular
respiration ↑ CO2)
CA
 CO2 + H2O  H2CO3  H+ + HCO3-
 H+ + Hb  HbH (Hb is a buffer)
 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)
 Process:
b. Inside RBC at pulmonary capillaries (i.e. at capillaries in
respiratory zone of lungs, where CO2 level are low)
 O2 + deoxyHb  HbO2 (note: deoxyHb can be HbH or
HbCO2)
 Low PCO2 in the alveoli, moves dissolved CO2 out of
the blood plasma, which promotes the reverse reaction:
CACO + H O
H+ + HCO3-  H2CO3 
 2 2

 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 Modified from Figure 18.11
membrane into the alveoli so that it can be expired).
 Minute ventilation (L/min)
60

G) Regulation of Respiration 40
 It is important to precisely regulate minute alveolar
20 normal PO2
ventilation in order to maintain normal arterial P O2
and PCO2 levels. 0
20 40 60 80 100 120 140
 Breathing rate and depth are under both voluntary Arteriolar PO2 (mm Hg)

and involuntary control of the skeletal muscles

responsible for respiration:
 Diaphragm and external intercostals for normal
“quiet” inspiration (i.e. breathing at rest)
 Sternocleidomastoid and scalenes are recruited
during forced inspiration (e.g. taking deep breaths,
such as during exercise).
 Quiet expiration occurs due to relaxation of external
intercostals and diaphragm.
 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
 Set the rate depth and rhythm of breathing.
 2 main groups of neurons that form the central pattern generator
a. Ventral Respiratory Group (VRG)
 contains an area call the pre-Bötzinger complex which generates
the rhythmic rate of breathing (pacemaker)
 has both inspiratory and expiratory neurons Similar to Figure 18.14
b. Dorsal Respiratory Group (DRG)
 receives sensory information from stretch receptors in the lungs,
and central and peripheral chemoreceptors
 modulates basic rhythm by signalling changes to VRG
2. Pontine respiratory centres
 Work with medullary centers to make breathing smooth and even.
 Damage to pontine respiratory centres produces short gasping,
Similar to Figure 18
irregular breaths.
 G) Regulation of Respiration
3. Voluntary Control
 Primary motor cortex in cerebrum signals to lower motor neurons
going to muscles of inspiration (bypasses medulla).
 If medulla is damaged – must remember to breathe
 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
 In smooth muscle of bronchi and bronchioles. Figure 18.13
 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
 Glomus cells in the carotid and aortic bodies (similar location to the
baroreceptors monitoring blood pressure) are in direct contact with arterial
blood
 Strongly activated when plasma PO2 drops below 60 mmHg (emergency
situation)
 More often stimulated by increases in both arterial PCO 2 and/or [H+]
 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.
 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).
 In CO poisoning, Hb has a much greater affinity for CO than for O 2. So at
the lungs, Hb binds preferentially to CO instead of O 2 forming
Figure 18.16
G) Regulation of Respiration
5. Chemical control (chemoreceptors)
b. Central chemoreceptors
 Located in the medulla , these neurons largely dictate the
respiratory pace at rest.
 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).
 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
 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 PCO 2 and
increase PO2, to normal levels in the blood plasma.
 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
 G) Regulation of Respiration
 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
 For example, if you try to hold your
breath for as long as possible, PCO2
increases and is converted into H+ in the Peripheral Central
medulla. This triggers the central Chemoreceptors chemoreceptors
chemoreceptors, which signal to the (glomus cells)
medullary respiratory centres to increase
ventilation rate. Firing of inspiratory Negative feedback will
*
Negative feedback will
neurons will override the voluntary return PO2 levels to within ↑ Ventilation return PCO2 levels to
control from the cerebral cortex and you set point range. within set point range.
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
 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
 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.).