Physiology of Hypoxemia

Corey D. Kershaw, M.D.

February 20, 2015

Physiological Causes of Hypoxemia

Hypoventilation

Diffusion impairment

Ventilation-perfusion (V/Q) mismatching

Right-to-left shunting versus dead space

Reduced inspired oxygen tension (altitude)

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

Alveolar Ventilation Equation

.

PaCO2 = VCO

2x K

VA

.

Expired minute ventilation

(or ventilatory demand)(1-VD/VT)

VA

.

=

PAO2

= FiO2 x [Patm - PH2O] -PaCO

2

R

Alveolar Gas Equation

** A-a = 149 – (PaO2 + PaCO2 + .25PaCO2)**

**Use this form if the patient is NOT on supplemental oxygen (on “room air”)

Why is there a “normal” A-a gradient?

PAO2

= FiO2

x [Patm - PH2O] -PaCO

2

R

.

PaCO2 =VCO

2x K

VA

.

If alveolar ventilation decreases, the PaCO2 rises…

And, if PaCO2 rises, PAO2 falls (and as a result PaO2 falls similarly)

Hypoventilation as a cause of hypoxemia

Alveolar Gas Equation, graphically

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

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

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

Dead space

Shunt

There are different degrees of V/Q mismatching

Effect of shunt on PO2

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!

Hypoxemic vasoconstriction

Dead space

Shunt

There are different degrees of V/Q mismatching

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

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

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”

Alveolar ventilation/PaO2 relationship

Increasing alveolar ventilation has very little impact on PO2

(“alveolar dead space”)

Interval Summary

• Primary causes of hypoxemia

– V/Q mismatching

• And, the extreme example of the RL shunt

– Diffusion impairment

– Hypoventilation

• Worsening dead space ventilation results in increased alveolar ventilation

– Little impact on PO2

Disease States and Hypoxemia

• COPD

• Pulmonary Edema

• Fibrosing ILD, such as IPF

Hypoxemia in COPD

Regional differences in gas exchange

V/Q ratio in a normal patient

Hypoxemia in COPD

V/Q ratio in patient with emphysema & chronic bronchitis

V/Q mismatching and changes on PO2

Hypoxemia in Pulmonary Edema

Chiefly due to shunt physiology

Hypoxemia in Pulmonary Edema

Ventilation obstructed by edema fluid, lowering alveolar PO2

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

Hypoxemia in Fibrosing ILD

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

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

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

PAO2

= FiO2 x [Patm - PH2O] -

PaCO2

R.

PaCO2 = VCO

2x K

VA

.

Expired minute ventilation

(or ventilatory demand)(1-VD/VT)

VA

.

=