The Respiratory System - Washington State University

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Transcript The Respiratory System - Washington State University

The Respiratory System
Gas Exchange
Behavior of Gases
• PV = nRT
– Where P = pressure
– V= volume
– n = the number of moles of gas
– R = the universal gas constant (22.4
liters/mole deg. Atm)
– T = temperature in deg. Kelvin
Partial Pressure
• The total pressure of a gas mixture is the
sum of the partial pressures of its
constituents, so
• The partial pressure of a single gas is
determined by multiplying the % of that
gas by the total pressure.
Gas composition of clean dry air at
sea level (PT = 760 mmHg)
Nitrogen
78.08%
593.4 mmHg
Oxygen
20.95%
159.22 mmHg
Inert gases
0.96%
7.34 mmHg
Carbon Dioxide 0.03%
0.24 mmHg
Water vapor is an important respiratory gas
• As air passes through the airway, it is
warmed and becomes saturated with
water vapor
• At 37o and 1 atm, the partial pressure of
water vapor is 47 mmHg.
• Addition of water vapor diminishes the
partial pressures of all the other gases,
compared to dry air
Gases in solution
• In a gas-water equilibrium, the partial pressure
of gas in solution becomes equal to the partial
pressure of the gas in the gas phase,
BUT
• The concentration of gas in solution does not
become equal to the concentration in the gas
phase; instead, the concentration is determined
by the partial pressure multiplied by the solubility
coefficient and the temperature.
The solubility coefficients and diffusion
coefficients of oxygen and carbon dioxide
differ greatly
• The solubility of CO2 in plasma at 37o is
about 21X that of oxygen
• The diffusion coefficient for CO2 in plasma
at 37o is about 20X that of oxygen
• These facts will have large implications for
gas exchange in the lungs and gas
transport in the blood
Gas compositions of alveolar air and pulmonary blood
Mixed
systemic
venous
blood
Systemic arterial
blood – generally
has equilibrated
with alveolar gas
Forms of gas in bloodstream
Systemic
arterial
Mixed systemic
venous
Arteriovenous
difference
100 mmHg
0.3 vol%
19.5 vol%
19.8 vol%
40 mmHg
0.1 vol%
14.4 vol%
14.5 vol%
60 mmHg
5.3 vol%=
265 ml/min for
a CO of 5L/min
40 mmHg
2.7 vol%
43.9 vol%
2.4 vol%
49.0 vol%
46 mmHg
3.1 vol%
47.0 vol%
3.9 vol%
54.0 vol%
6 mmHg
5.0 vol% = 250
ml/min for a
CO of 5L/min
Oxygen
PO2
Physical solution
Bound to hemoglobin
Total
Carbon Dioxide
PCO2
in physical solution
As bicarbonate
As carbamino Hb
Total
Oxygen transport
Oxygen transport by Hemoglobin (Hb) and
Myoglobin (Mb)
• Evolution of O2 transport proteins necessitated
by the poor solubility of O2 in water
• Hb is a tetramer composed (after birth) of two
alpha globin chains and two beta globin chains =
4 binding O2 binding sites – the binding sites
exhibit cooperativity
• Mb is an intracellular transport protein
composed of a single globin chain = 1 binding
site, so no cooperativity
% saturation
The Hb-O2 dissociation curve
Implications of the Hb-O2
dissociation curve
• Hb is about 98% saturated at the PO2 of
systemic arterial blood.
• Normal variations in the PO2 of alveolar gas have
little effect on the O2 content of arterial blood
• On average, about ¼ of the total O2 carried by
arterial blood is delivered to the tissues in each
pass through the systemic loop.
• Individual organs and tissues can extract more
or less than ¼ of the oxygen, depending on their
metabolic rate and other factors.
Five factors can modulate the amount of O2
unloaded
•
•
•
•
•
1. the PO2 of the tissue itself
2. increased temperature
3. decreased pH (called the Bohr effect)
4. increased PCO2
5. increased plasma levels of 2,3
diphosphoglycerate (2,3 DPG)
• The last four factors act by shifting the rising part
of the curve to the right, causing more O2 to be
unloaded at any tissue PO2.
Right shifting the curve increases unloading,
without affecting loading
The route for oxygen from lungs to
mitochondria
Alveolar gas
diffusion
Capillary RBCs
Hemoglobin binding, convective transport
in bloodstream
diffusion
Interstitial fluid
diffusion
Cytoplasm
Facilitated diffusion
(Mb)
mitochondria
Carbon Dioxide Transport
Plasma CO2 exists in equilibrium with its
other chemical forms
• CO2+H2O
H2CO3
Carbonic anhydrase
H+ + HCO3-
• Ka = [H+][HCO3-]/[H2CO3]
= [H+][HCO3-]/[CO2][H2O]
Plasma pH is described by the HendersonHasselbalch equation
• H-H eq describes the equilibrium state of
the buffer system
normal arterial value is 24 mEq/L
• pH = 6.1 + log [HCO3-]/0.03PCO2
pKa of H2CO3
Solubility
Coefficient of
CO2
Normal arterial
value is 40
mmHg
Facts
• The bicarbonate buffer system with a pKa
of 6.1 is, from a chemist’s point of view, a
crummy choice for an arterial plasma pH
of 7.4 – but we never run out of the
ingredients!
• The buffer system is “open” – so plasma
PCO2 is set by alveolar PCO2
CO2 transport by Hb
• No transport protein is really needed for
CO2,because it is so water-soluble – but to a
limited extent, Hb is also a CO2 transport protein
because of the formation of carbaminoHb.
• CarbaminoHb has a lower affinity for O2 than Hb
(remember, binding CO2 causes the Hb
dissociation curve to shift to the right) – so when
a RBC passes through a systemic capillary,
formation of carbaminoHb forces additional O2 to
be unloaded.
Hb buffering, carbonic anhydrase and the
chloride shift facilitate CO2 loading
• Hb is a buffer – but both deoxyHb and
carbaminoHb are even better buffers than Hb
• When CO2 diffuses into a RBC, it rapidly
dissociates (catalyzed by carbonic anhydrase),
releasing some H+, which is accepted by the Hb.
• This leaves HCO3-, which would build up in the
RBC and cause the process to grind to a halt,
except for a process called the chloride shift, in
which HCO3- is transported out of the RBC in
exchange for Cl- by an anion exchanger in the
plasma membrane.
CO2 unloading in pulmonary capillaries is the
reverse of CO2 loading in pulmonary capillaries
• Each RBC spends less than 1 second in a
pulmonary capillary – so it is remarkable that
gas equilibrium can be attained in so short a
time.
• Because of the short time scale, the carbonic
anhydrase in RBCs is especially important for
this process.