The document discusses the physiological causes of hypoxemia, including hypoventilation, ventilation-perfusion (V/Q) mismatching, and diffusion impairment. Hypoxemia can result from decreased alveolar ventilation leading to higher PaCO2 and lower PAO2, or from V/Q mismatching like shunts or dead space. Disease states like COPD, pulmonary edema, and fibrotic lung disease cause hypoxemia through various combinations of V/Q mismatching and diffusion impairment. Understanding the alveolar gas and ventilation equations is key to determining the root cause and response to hypoxemia in clinical practice.

1. Physiology of Hypoxemia
Corey D. Kershaw, M.D.
February 20, 2015

2. Physiological Causes of Hypoxemia
Hypoventilation
Diffusion impairment
Ventilation-perfusion (V/Q) mismatching
Right-to-left shunting versus dead space
Reduced inspired oxygen tension (altitude)

3. O2 partial pressures from air to tissues
• PO2 falls as gas moves
from the air to
mitochondria
• Determinants of PO2
– Rate of removal of
oxygen by pulmonary
capillary blood
• Set by metabolic
demands of the tissues
– Rate of replenishment
by alveolar ventilation

4. Alveolar Ventilation Equation
.
PaCO2 =
VCO2 x K
VA
.
Expired minute ventilation
(or ventilatory demand)
(1-VD/VT)
VA
.
=

5. PAO2
= FiO2 x [Patm - PH2O] -
PaCO2
R
Alveolar Gas Equation
** A-a = 149 – (PaO2 + PaCO2 + .25PaCO2)**
**Use this form if the patient is NOT on supplemental oxygen
(on “room air”)

6. Why is there a “normal” A-a gradient?

7. PAO2
= FiO2
x [Patm - PH2O] -
PaCO2
R
.
PaCO2 =
VCO2 x K
VA
.
If alveolar ventilation decreases, the PaCO2 rises…
And, if PaCO2 rises, PAO2 falls (and as a result PaO2 falls
similarly)

8. Hypoventilation as a cause of hypoxemia
Alveolar Gas Equation, graphically

9. Diffusion Impairment
• For oxygen to reach
the pulmonary
capillary, it must
traverse the
interstitium
• Determinants include
thickness of the
interstitium and the
rate of capillary blood
flow

10. Diffusion Impairment
• For oxygen to reach
the pulmonary
capillary, it must
traverse the
interstitium
• Determinants include
thickness of the
interstitium and the
rate of capillary blood
flow

11. Diffusing capacity is further determined by both the capacity of the
membrane, the volume of blood in the capillaries, AND the rate of reaction
between the oxygen molecule and hemoglobin

12. Dead space
Shunt
There are different degrees of V/Q mismatching

13. Effect of shunt on PO2

14. Effect of right-to-left shunt on arterial
oxygenation
Note, on graph B, that in the presence of a 50% R-to-L shunt, increasing the FiO2 from
room air to 100% (or PIO2 from 150 to 760) results in only an increase in PaO2 by 12!

15. Hypoxemic vasoconstriction

16. Dead space
Shunt
There are different degrees of V/Q mismatching

17. Types of Dead Space
A. Anatomic
The only areas
where gas
exchange does not
take place are the
conducting airways
B. Physiologic
Not all ventilation
units are coupled
to pulmonary
blood flow

18. Dead Space and
Ventilatory Demand
Point A – Normal Values
for VD/VT, PaCO2, and VE
Point B – Effect on VE when
VD/VT increases from 0.3
to 0.75. Dramatic increase
in ventilation required to
maintain a normal PaCO2
Point C – To push the
PaCO2 even lower, the
ventilatory requirement
increases exponentially for
a given VD/VT

19. In case you’re wondering…
• V/Q mismatching rarely causes a disruption in
PaCO2. Why?
• Ventilatory drive (stimulated by
chemoreceptors) is exquisitely sensitive to
rising PaCO2
• Further, this increased ventilation is “wasted”
on normal alveolar units
– “alveolar dead space”

20. Alveolar ventilation/PaO2 relationship
Increasing alveolar ventilation has very little impact on PO2
(“alveolar dead space”)

21. Interval Summary
• Primary causes of hypoxemia
– V/Q mismatching
• And, the extreme example of the RL shunt
– Diffusion impairment
– Hypoventilation
• Worsening dead space ventilation results in
increased alveolar ventilation
– Little impact on PO2

22. Disease States and Hypoxemia
• COPD
• Pulmonary Edema
• Fibrosing ILD, such as IPF

23. Hypoxemia in COPD

24. Regional differences in gas exchange

25. V/Q ratio in a normal patient

26. Hypoxemia in COPD

27. V/Q ratio in patient with emphysema &
chronic bronchitis

28. V/Q mismatching and changes on PO2

29. Hypoxemia in Pulmonary Edema
Chiefly due to shunt
physiology

30. Hypoxemia in Pulmonary Edema
Ventilation obstructed by
edema fluid, lowering
alveolar PO2

31. Hypoxemia in Fibrosing ILD
A combination of V/Q
mismatching as well as
diffusion impairment
Ventilation and
perfusion are regionally
reduced by the
destructive fibrotic
disease

32. Hypoxemia in Fibrosing ILD

33. Diffusing capacity is determined by both the capacity of the membrane, the
volume of blood in the capillaries, AND the rate of reaction between the
oxygen molecule and hemoglobin

34. PO2 against time in the pulmonary capillary. Note that with exercise/exertion, the
time for oxygenation reduces drastically (“diffusion limitation”)

35. Summary
• In clinical practice, three primary physiological
causes of hypoxemia
– Hypoventilation
– V/Q mismatching (primarily via R->L shunting)
– Impaired gas diffusion
• In reality, most disease states lead to hypoxemia
by more than one mechanism
• Keeping the alveolar gas and alveolar ventilation
equations handy can go a long way in
determining the cause of and response to
hypoxemia

36. PAO2
= FiO2
x [Patm - PH2O] -
PaCO2
R
.
PaCO2 =
VCO2 x K
VA
.
Expired minute ventilation
(or ventilatory demand)
(1-VD/VT)
VA
.
=