Advanced Human Physiology course
LS607
Module 6
Gas Exchange and
Respiratory Physiology (2)
16 Oct 2023
Diffusion of O2 from Alveoli to the pulmonary capillary blood
Ø All O2 diffusion occur in the first third of the capillary.
Exercise requires 20 -mes the normal amount of O2
Cardiac output à Time blood remaining in capillary reduced to half
Ø How is the uptake of O2 maintained high by the
pulmonary blood during exercise?
Surface area of capillaries Safety margin
O2 diffusing capacity (x3)
V/Q in upper part of lungs
Δ𝑃 . 𝐴 . 𝑆
𝐷∝
𝑑 . 𝑀𝑊
O2 transport through the arterial tree
Ø Shunt flow: 2% of the blood is not exposed to gas PaO2 95 mmHg
exchange in the lungs (bronchial circulaJon)
Ø PO2 of the shunt blood is 40 mmHg
PO2 104 PO2 40
mmHg mmHg
PO2 95
mmHg
Diffusion of O2 from capillaries into the :ssue fluids and cells
IntersJJal fluid = PO2 40 mmHg
Tissue cells = PO2 23 mmHg
Ø The intracellular chemical process needs only PO2
of 1-3 mmHg à There is a large safety factor
Blood flow
in tissue
PO2 in the
intersJJal fluids
Tissue
metabolism rate
Transport of CO2 from Tissues into capillaries à Pulmonary capillaries à alveoli
Ø CO2 diffuse about 20 times as rapidly as O2
PCO2 in cells – PCO2 in intersJJal fluid = 1 mmHg
Blood flow PCO2 IntersJJal fluid
Tissue metabolism PCO2 IntersJJal fluid
Similar values to
arterial blood
Hemoglobin
Ø 97% of Oxygen transported from the lungs to the tissues is
carried chemically with hemoglobin in red blood cells.
Ø The oxygen molecules bind loosely and reversibly to the heme
groups on each of the four subunits of the hemoglobin
molecule.
Ø Each hemoglobin molecule therefore has the capacity to bind
four molecules of O2 à 100% saturation
15 g hemoglobin per 100ml blood
1 g hemoglobin 1.34ml O2
15 g hemoglobin/ 100 ml x 1.34 = 20.1 ml O2 (Maximum amount of O2 that combines with Hb)
Positive affinity cooperativity of O2 to hemoglobin
➕ O2 O2
O2 O2 O2 O2 O2
➕
O2 O2
➕ O2
0 25% O2 50% 75% 100%
O2 binding Affinity
Oxygen-Hemoglobin dissocia:on curve
Ø SaturaJon (%) increases steeply as PO2 increases from zero to approximately
40 mm Hg, and it then levels off between 50 mm Hg and 100 mmHg
Sigmoidal Shape?
P50 Affinity
ity
ffin
in a
nge
ch a
Ø Under normal condiJons, 5 ml of O2 are transported
from the lungs to the Jssues in each 100 ml blood flow
Ø During heavy exercise, 15 ml of O2 are transported to
P50
the Jssues in each 100 ml blood flow
Factors that shift the Oxygen-Hemoglobin dissociation curve
In Exercise
Glucose
ATP Muscles Low affinity Lungs High affinity
Pyruvate
DPG (2,3-biphosphoglycerate)
Pulse oximetry
• Measure arterial O2 saturaJon (SO2%)
• Different absorbance for Hb-O2 and Hb.
• Records only data with pulse (arterial capillaries)
Transport of CO2 in the blood
Ø Under normal conditions, 4ml of CO2 are transported from the tissues to the lungs in each 100 ml of blood
PvCO2 = 45 mmHg
Ø 7% CO2 is transported in dissolved state PaCO2 = 40 mmHg
to the lungs
Ø Hemoglobin is an acid-base buffer
Ø HCO3/Cl carrier protein shuttles the two
ions
Carbonic acid
Cl- (venous) > Cl- (arterial)
Ø Carbaminohemoglobin (CO2Hb):
CO2 reacts with amine radicals of
hemoglobin
CO2 dissocia:on curve
Ø Haldane Effect
When O2 binds with Hb, Hb is becoming more acidic. CO2 is released
Narrow range
Ø Bohr Effect
Increase of CO2 in blood à O2 is displaced from hemoglobin (to
enhance releasing O2 to tissues and lung oxygenation)
Shift because of Haldane effect
Ø Haldane effect is very important for efficient CO2 transport from Jssues to the lungs
Respiratory center
Ø Breathing is an involuntary process that is controlled by the medulla and pons of the brain stem.
Repe--ve bursts of
Dorsal Respiratory
Inspiratory neuronal Basic rhythm of respira-on
Group (DRG)
ac-on poten-als
Ramp signal: begins weakly and
increases steadily in a ramp
manner for about 2 seconds in
normal respiration and ceases
for the next 3 seconds.
Ventral respiratory Pneumotaxic Center
group • Limits the duraJon of To abdominal
inspiraJon muscles
o InacJve à quiet • Respiratory rate:
breathing - Strong signal à BR ⬆ Phrenic nerve to
o Heavy breathing à - Weak signal à BR ⬇ diaphragm
Hering-Breuer
expiratory signals to
inflaEon reflex
abdominal muscles • Peripheral chemoreceptors
Stretch receptors in
lungs • Baroreceptors
Chemical control of respiratory center
Ø Chemosensitive area beneath the ventral surface of the medulla
Ø Highly sensiJve to blood CO2 and H+ ions but H+ is the main sJmulus
Ø Blood Brain Barrier is not very permeable H+
Ø Changes in blood CO2 has a potent acute effect on respiraJon but
only weak chronic effect aGer few days adaptaEon.
Ø The change of blood CO2 level causes a
bigger increase of alveolar venJlaJon
than of H+
Ø Changes in O2 have ligle effect on control of respiratory center.
Peripheral chemoreceptor system for control of respira:on
Ø This system is high sensiJve to O2 changes and
detects the PO2 of the arterial blood Carotid body structure
Ø Decreased PaO2 level induces the initiation of
nerve impulse transmission from carotid
bodies.
Ø The changes in CO2 and H+ also can
sJmulate the chemoreceptors but
respiraJon center is more sensiJve
Ø The response for the changes in CO2 and H+ is
five Jmes more powerful by the
chemoreceptors than the respiraJon center
30-60 mmHg
Direct supply from
Hb saturaJon⬇ arterial blood
Molecular mechanism of stimulation of the chemoreceptors by O2 reduction
PaO2
O2-potassium channel
Membrane depolarizaJon
Open Ca2+ channels
Intracellular Ca2+
Sensor cell
Release neurotransmiger
AcJvaJon of afferent neuron
Signal to respiratory center
Respiratory rate
The effect of PaO2 change on the alveolar ventilation if CO2 and H+ are normal
Ø PCO2 and H+ response are mainly
responsible for regulaJng venJlaJon in
healthy humans at sea level
Acclima:za:on
Ø Chronic breathing of low O2 sJmulates the breathing more
High alJtude
PaO2
Carotid bodies
Respiratory center
Respiration
Acclima:za:on
Ø Chronic breathing of low O2 sJmulates the breathing more
High alJtude
H+ PCO2 PaO2
Carotid bodies
Respiratory center
??
RespiraJon
Acclima:za:on
Ø Chronic breathing of low O2 sJmulates the breathing more
High altitude
(Respiratory PaO2
H+ PCO2
Alkalosis)
Carotid bodies
Respiratory center
Kidney
RespiraJon
HCO3 –
EliminaJon in urine
Ø Respiratory center loses their sensitivity to CO2 changes
within 2-3 days.
Ø The kidneys increases alkaline bicarbonate excreJon in the
urine, which compensates for the respiratory loss of acidity
(few days)
