• Bring balloons and let students blow into
balloons
• Bring a carbonated beverage
• Bring two pieces of transparency film for
suction experiment
• Bring oximeter
Pressure of gases
• P = Pressure produced by
molecules hitting the walls of a
chamber:
• P = R (n/V) T
–
–
–
–
–
n = number of particles
V=volume
(n/V) = concentration
T = temperature in Kelvin
R = 1.987 cal K-1 mol-1 (gas
constant)
• If you add another gas to the
same compartment, P↑ in
proportion to the number of
molecules (n). Pressure does not
care for the kind of gas. If n is
doubled  P is doubled.
Dalton’s law: the pressure exerted by each gas is independent
of pressure exerted by other gases
• (this is because gas molecules are so far apart that they do
not interfere with each other)
• Ptotal = Pgas1 + Pgas2 + Pgas3 + …
• these individual pressures are called partial pressures
• Example: Pair = P02 + PN2 = 160 + 600 = 760 mm Hg
• P02 / Ptotal = 100% · 160/760 = 21%
• PN2 / Ptotal = 100% · 600/760 = 79%
• PCO2 / Ptotal =100% · 0.3/760= 0.04%
160 mm Hg
600 mm Hg
760 mm Hg
Gas dissolved in water
• When water is exposed to air containing a particular gas, molecules of the
gas will enter water and dissolve in it.
• Give me a few examples of a gas dissolved in water?
– carbonated beverages: CO2 is dissolved in all carbonated
beverages, agitate the bottle and observe CO2 coming out.
– Oxygen dissolved in water is used by fish for respiration
• In other words, Pgas in air = Pgas in water at equilibrium
• Examples: in sea water P02 =? PCO2 =?
• Henry’s law: in equilibrium the mass of gas dissolved is proportional to
partial pressure of the gas:
• [gas] = Pgas · solubility
• solubility of O2= 0.03mL / 1L / mmHg
• solubility of CO2= 0.6mL / 1L / mmHg
• solubility of CO2 in water is 20 fold greater than solubility of O2
• If PO2 =PCO2 then there is 20 time more CO2 molecules than O2 molecules
dissolved in water
• [O2] on blood at sea level = 160 mm Hg · 0.03mL/1L/mm Hg = 4.8mL / 1L
Respiratory system homeostasis
plant
Breathing
feedback
control
Sensors in medulla in
brainstem
sensors
[CO2]=const
controlled variable
to a lesser extent
O2 and [H+]
[H+] (in mM)=24PCO2/[HCO3-] (in nM)
• Take a deep breath and … relax
all your muscles What happens?
• Aren’t you surprised that with all
muscles relaxed, the air is being
pushed out of you lungs (repeat
using your palm to feel the air
flow)
• Lung elastic recoil is driving
expiration, NOT muscles.
(muscles stay completely
relaxed, i.e. it is a passive
process)
• Think of the lung as a rubber
balloon. Every time you take a
breath, the lung wants to recoil
back to its un-inflated state.
• We say the lung has elastic recoil,
just like an elastic balloon.
Think of the lung as a rubber balloon
The balloon is inflated and glued to
the chest wall during inspiration
The balloon wants to recoil. To prevent
the recoil, you flex the diaphragm
Think of the lung as a rubber balloon
As soon as you relax the diaphragm, the lungs recoil  Expiration
volume of fresh
air brought in =
tidal volume =
500mL
•
•
•
•
To take the next breath, flex the diaphragm  diaphragm pulls on the lungs  Inspiration
We can also use muscles between ribs to expand the chest by flexing external intercostals
or to decrease chest volume by flexing internal intercostals
We say: the lung sits in the thoracic cavity. During inspiration  ↑ thoracic volume 
negative pressure (relative to atmospheric 760mm Hg  air flows into the lungs
What connects lungs to the wall of thorax?
filled with water
• Nothing!
• [Experiment with
two pieces of
transparency film]
• Lungs are
connected to the
wall of the thorax
by suction.
First submarines lacked adequate air and power supplies, and
were unable to easily lift from the seafloor.
Some captains who experimented with landing on the sea floor
are still there … water suction prevented their lift from the
seafloor.
Pneumothorax
• Knife, bullet, shrapnel, or broken rib punctures
the pleura  lung recoils, chest expands
• Tension pneumothorax
• In 1999 movie Three Kings Mark
Wahlenberg’s character “Troy” is
shot and suffers from tension
pneumothorax
• Every marine carries a tension
release needle
Lung
morphology
• Bronchi (singular
bronchus) divide 2425 times 
enormous crosssection for easy gas
movement
• Gas exchange occurs
in alveoli
• There are 300
million alveoli
• diameter of
alveolus =
0.3mm
• total gas
exchange
surface area =
75 m2
(=combined
area of three
classrooms)
• Why such a
large area?
• To facilitate
gases exchange
Major functions of respiratory system:
• O2 exchange and CO2 exchange
ambient air:
PO2= 160 mm Hg
PCO2= 0.3 mm Hg
VT is not added to emptiness. It
is added to the gas that is left in
the lungs (~3L)  usually only
1/6 of fresh air is brought into
the lungs
PO2= 100 mm Hg
PCO2= 40 mm Hg
PO2= 40 mm Hg
PCO2= 46 mm Hg
PO2= 100 mm Hg
PCO2= 40 mm Hg
PO2= 100 mm Hg
PCO2= 40 mm Hg
PO2= 40 mm Hg
PCO2= 46 mm Hg
4.5 – 6 Liters
if paralyzed or dead
volume will go to FRC
1.5L cannot move it out
• During an exercise we need more oxygen  we have to bring
more fresh air:
– We increase the number of breaths per min a little bit
– Mostly we ↑ the volume of fresh air that we breathe in with each
breath
7Liters
How oxygen is carried in blood?
• Some oxygen is dissolved in the blood
plasma
• in 1 liter of oxygenated (arterial) blood
– 3 mL of O2 is physically dissolved
– 197 mL of O2 is bound to Hb
• Hemoglobin (Hb) plays a role of high
capacity buffer. It absorbs O2 as a sponge
absorbs water
O2
0.2µm
• In systemic circulation, as O2 dissolved in
plasma diffuses into tissue:
 PO2 ↓ in plasma
 PO2 ↓ in RBC
 O2 molecules dissociate from Hb and
move into plasma
 PO2 ↑ in plasma
Hemoglobin (Hb) has 4 subunits
• Hb is a very special molecule:
its affinity to O2 (that is how
strong it binds O2) depends on the
number of bound O2 molecules
• In oxygenated blood
(PO2=100mm Hg) Hb binds 4 O2 molecules
• As it goes through tissues and releases its 1st O2
molecule, the 2nd O2 molecule is released easier, the 3d
even more easier, and the 4th even more easier
• This effect occurs because there is positive
cooperativity between subunits: as one subunit
releases O2, it changes its conformational shape
 this change in shape reduces other subunits affinity
to O2  and so forth
Hemoglobin saturation (%)
100% 4 O2
75% 3 O2
=1 molecule of O2
by every Hb
molecule
50% 2 O2
25% 1 O2
in moderately
active tissue
0
• This positive cooperativity can be represented on a graph that
relates the number of O2 molecules held by Hb to PO2
Oximeter
• Who has the highest oxygen saturation?
• Who has the lowest oxygen saturation?
• DPG  Lance
Armstrong doping case
Hemoglobin saturation (%)
100% 4 O2
75% 3 O2
↑T, ↑[DPG],
↑H+, ↑[CO2]
50% 2 O2
=1 molecule of O2
by every Hb
molecule
25% 1 O2
in moderately
active tissue
0
• How many O2 molecules are released by every Hb in tissue with
↑T, ↑[2,3-diphosphoglycerate], ↑H+, ↑[CO2] (the thick curve)?
• 3 molecules of O2 instead of 1  tissue gets more O2
Notice how smart tissues
regulate their O2 supply:
• Active muscles 
– use O2  PO2 in ECF ↓
– release CO2  PCO2 in ECF ↑
– release lactic acid  [H+] ↑
– temperature ↑
 open precapillary
sphincters  tissue
receives more blood
 change molecular
properties of Hb 
Hb releases more O2
Precapillary sphincters
are relaxed by:
Hb affinity for O2 is
reduced by:
↓PO2
↑PCO2
↑ [H+]
↑ osmolarity
↑ adenosine
↓PO2
↑PCO2
↑ [H+]
↑temperature
• Conclusions: (1) tissue receives more blood and
• (2) each RBC gives up more O2 molecules
Myoglobin
•
•
•
•
Muscles also have their own O2 buffer:
Myoglobin has higher affinity to O2 than Hb
Therefore at any PO2, O2 will jump from Hb to Mb
Myoglobin is analogous to sponge that sacks all O2 from Hb
normal PCO2 =
0.3 mm Hg =
0.04% of air by
volume
PCO2=0.03x760mm
Hg=20mmHg
PCO2 = 35mm Hg
PCO2 = 60mm Hg
Examples of CO2 toxicity
• In Israel during 1st Gulf war: sealed kitchen + turned on gas
for heating  two people sleep in the kitchen  both die
• Because CO2 is heavier than air, in locations where CO2 seeps from the
ground (due to sub-surface volcanic or geothermal activity) in high
concentrations, CO2 can cause animals and humans to be suffocated: on
August 21, 1986, Lake Nyos in Cameroon released of about 300,000
tons of CO2; this cloud rose at nearly 100 km per hour. The gas spilled
into a valley and suffocating 3,500 livestock as well as 1,700 people.
 transport CO2 out of the body
1. 10% of CO2 is dissolved in blood plasma
– (compare to O2 : only 1.5% of O2 is dissolved in blood plasma.
Solubility of CO2 in water is 20-fold greater than solubility of O2)
– 26mL of CO2 is dissolved in 1L of blood (only 3mL of O2)
2. 30% bound to amine group of Lysine and Arginine (amino
acids that build Hb).
– carbaminoHb
– R-NH2 + CO2 <-> R-NH-COO- + H+
3. 60% as bicarbonate HCO3-
– CO2 + H2O <-(slow reaction)-> H2CO3 <-> HCO3- + H+
– the slow reaction is catalyzed by
carbonic anhydrase concentrated in RBC
• In alveoli CO2 is released into air simply
because PCO2 in blood 46 mm Hg is higher
than PCO2 in the lungs 40 mm Hg
Carbon Monoxide (CO)
• CO is a colorless, odorless, and tasteless gas that is
slightly less dense than air.
• breathe in air with 1% of CO
 unconscious after 2-3 breathes  death in 5 minutes
• in the past, motor car exhaust may have contained up to 25% CO. Newer
cars have catalytic converters which eliminate 99% of CO produced.
However even cars with catalytic converters produce enough CO to kill if
the car is left idling in enclosed space.
• CO is produced by burning firewood
 firemen sometimes suffer brain damage; occipital lobe is first to die…
• What is going on?
• CO has higher affinity to Hb than O2. CO binds 240 times tighter to Hb  CO
essentially displaces O2. Once CO is bound to Hb, Hb cannot carry any O2.
Arterial blood still has PO2=100mm Hg, but total [O2]=1.5% of normal. That
3mL of O2 is still dissolved in oxygenated blood, but the Hb buffer has no O2.
When blood travels to tissue, this dissolved O2 quickly diffused to tissue and
there is no O2 to replace plasma dissolved oxygen.
• CO is produced in the process of Hb recycling  1% of Hb is usually bound
to internally produced Hb. In smokers up to 10% of Hb is bound to CO.
Sensors
• Two sets of
chemoreceptors:
1. central (in medulla,
close to medulla
respiratory control
center)
2. peripheral (sinuses
of carotid arteries
and the arch of
aorta – these are
physically close but
distinct from
arterial
baroreceptors)
midbrain
• 3 substances to control:
change: CO2 change: O2
– CO2
– O2
– H+
• Which is the most
important for setting
ventilation?
• Experiments:
– fix O2, vary CO2 without
telling to a subject,
measure ventilation
– fix CO2, vary O2, measure
ventilation
• CO2 is most important for
setting ventilation rate
• makes sense  CO2
reflects activity level:
double activity level 
double CO2 production 
double ventilation
•
It looks like in a lot of cases this mechanism
does not kick in before humans die. There are
plenty of stories of humans walking into
deoxygenated chamber and dies without
feeling of danger
pH
•
Recall: 60% of CO2 is transported as
bicarbonate HCO3-
– CO2 + H2O <-(slow reaction)-> H2CO3 <->
HCO3- + H+
• Thus PCO2 and [H+] in blood are linked:
• [H+] (in mM)=24PCO2/[HCO3-] (in nM)
• Increased PCO2 immediately increases H+
and vise versa
• In fact chemoreceptors (both central and
peripheral) are sensitive to [H+]
• (the peripheral receptors, but not central
receptors are sensitive to PO2)
• Effects of increased PCO2 (hence increase
[H+]) and decreased O2 are independent
inputs to medulla. Their combined effect is
synergistic: it is considerably greater than
the sum of the individual responses.
• CO2 is most important for setting
ventilation rate. Acts on both peripheral
and central receptors via [H+].
• Respiratory muscles are skeletal
muscles  need input from
nerves
• In medulla there are two groups
of neurons working as pacemaker
that can be regulated by
chemoreceptors
• The biggest respiratory muscle is
diaphragm
• Inspiration  diaphragm is
stimulated by motor nerves in the
phrenic nerve (leaving spinal cord
on 3,4,5 cervical vertebra).
• If you need to increase ventilation
 double firing in motor neuron
• Expiration ?
• Expiration is passive  lung
elastic recoil pushes air out of
lungs.
• Emphysema: lungs
loose elastic recoil 
lungs stay inflated.
• Medulla control of PCO2 and
PO2 is reflexive
• These reflexes can be
overridden: for example, we
interrupt breathing to talk
and to sing.
• On the other hand, reflex is a
reflex: run for a mile, then
try to give a speech
 you cannot because
respiration is overriding the
attempt to speak.
Summary
plant
CNS
voluntary
input
feedback
control
Breathing
Sensors in medulla in
brainstem
[CO2]=const
controlled variable
to a lesser extent
O2 and [H+]
[H+] (in mM)=24PCO2/[HCO3] (in nM)
sensors
Functions of respiratory system:
• oxygen exchange
• CO2 exchange
• Regulates H+ (blood pH)
• Forms speech sounds
• Defends against microbes
(immune function)
• Traps and dissolves blood clots
Asthma
• Affects 7% population in USA
• Causes 4,000 deaths a year in USA
• Asthma attack is relieved by albuterol (quick-acting adrenergic receptor
agonist) that relaxes smooth muscle on bronchi
• Long-term asthma treatment: avoid exposure to allergens; reduce bronchi
inflammation with corticosteroids
• Practicing breathing exercise
• consider discussing both cardivascular and
respiratory HW
• Expiration is passive  lung
elastic recoil pushes air out of
lungs.
• Emphysema: lungs loose
elastic recoil  lungs stay
inflated.