[Costanzo] Ventilation/Perfusion

V/Q Mismatch

Mismatch of ventilation and perfusion causing abnormal gas exchange. A V/Q mismatch/defect can be caused by ventilation of lung regions that are not perfused (dead space), perfusion of lung regions that are not ventilated (shunt), etc.

Q2: What are the units of FEV1?

Milliliters or liters (Hint: FEV1 is the volume expired in the first second of forced expiration, not a fractional volume.)

V/Q Ratio

Ratio of alveolar ventilation (VA) to pulmonary blood flow (Q)

Definition of shunt

Refers to a portion of cardiac output or blood flow that is diverted or rerouted

Normal V/Q

0.8. This means that alveolar ventilation (L/min) is 80% of the value for pulmonary blood flow (L/min).

Q1: If tidal volume is 500 mL, inspiratory reserve volume is 3 L, and vital capacity is 5 L, what is expiratory reserve volume?

1500mL

Q4: A person at sea level breathes a mixture containing 0.1% carbon monoxide (CO). The uptake of CO was measured using the single breath method as 28 mL/minute. What is the lung diffusing capacity for CO (DlCO)?

39.3 mL/min/mm Hg (Hint 1: VCO = Dl x ΔP. Hint 2: PCO in room air = [Pb - 47 mm Hg] × 0.001, and PCO in blood is initially zero.)

Q3: Room air is a mixture of O2 and N2 saturated with H2O vapor. If barometric pressure is 740 mm Hg and the fractional concentration of O2 is 21%, what is the partial pressure of N2?

547.5 mm Hg (Hint: [740 - 47] × 0.79.)

Zone 1

As a result of gravity, PaO2 at the apex may be lower than PAO2. If Pa is lower than PA, the pulmonary capillaries will be compressed by the higher alveolar pressure outside of them. This compression will cause the capillaries to close, reducing regional blood flow.

Overview of the response to exercise of the respiratory system

As the body's demand for O2 increases, more O2 is supplied by increasing the ventilation rate: Excellent matching occurs between O2 consumption, CO2 production, and the ventilation rate.

Overview of adaptation to high altitude

Ascent to high altitude is one of several causes of hypoxemia. The respiratory responses to high altitude are adaptive adjustments a person must make to the decrease in PO2 in inspired air and alveolar air.

RBC concentration in response to high altitude

Ascent to high altitude produces an increase in RBC concentration (polycythemia) and as a consequence, an increase in hemoglobin concentration. This increase in Hb means that the O2 carrying capacity is increased, which increases the total O2 content of blood in spite of PaO2 being decreased.

Hypoxic vasoconstriction and birth

At birth, the neonate's first breath increases PAO2 to 100mmHg, hypoxic vasoconstriction is reduced, PVR decreases, and pulmonary blood flow increases and eventually equals cardiac output of the left side of the heart (as in the adult).

Pulmonary resistance in response to high altitude

At high altitude, alveolar gas has low PO2, which has a direct vasoconstriction effect on the pulmonary vasculature (i.e., hypoxic vasoconstriction). PVR increases, and thus pulmonary arterial pressure must increase to maintain a constance blood flow (which in the long run can cause RV hypertrophy).

Gas exchange in the presence of a shunt

Because no gas exchange can occur with a shunt, pulmonary capillary blood from these regions has the composition as mixed venous blood: PaO2= 40mmHg and PaCO2= 46mmHg.

Gas exchange in the presence of high V/Q

Because ventilation is high relative to perfusion, pulmonary capillary blood from these regions has a high PAO2 and low PACO2

Gas exchange in the presence of low V/Q

Because ventilation is low relative to perfusion, pulmonary capillary blood from these regions has a low PaO2 and a high PaCO2

CO and Pulmonary blood flow in response to exercise

CO increases to meet the tissues' demand for O2. Since PBF is the CO of the right heart, PBF also increases. There is a decrease in PVR associated with perfusion of more capillary beds, which also improves gas exchange. As a result, PBF becomes more evenly distributed throughout the lungs, and the V/Q ratio becomes more "even", producing a decrease in the physiologic dead space.

Leukotrienes

Cause airway constriction (as opposed to vasoconstriction).

Dead Space (V/Q= infinity)

Dead spar is ventilation of lung regions that are not perfused. This ventilation is wasted, or "dead". It is illustrated by *pulmonary embolism*

Integrative Functions

Go!

Mechanism by which PAO2 causes vasoconstriction.

If PAO2 is reduced to values between 100mmHg and 70mmHg, vascular tone is minimally affected. However, if PAO2 is reduced below 70mmHg, the vascular smooth muscle senses hypoxia, vasoconstricts, and reduces pulmonary blood flow to that area. It is believed that hypoxia depolarizes VSM cells, which in turn opens voltage-gated Ca++ channels and causes contractile activity to occur. There is also evidence that NO synthesis is blocked during hypoxia.

Consequence of a significant increase in PA relative to Pa (PAO2 > PaO2)

If arterial pressure is decreased (e.g., hemorrhage) or if alveolar pressure is increased (e.g. positive pressure breathing), then PA will be greater than Pa, and the blood vessels will be compressed and close. Under these conditions zone 1 is ventilated but NOT perfused. Thus, zone 1 becomes part of the physiologic dead space.

Consequence of right-to-left shunts

In a right-to-left shunt, hypoxemia ALWAYS occurs because significant fraction of the CO is not delivered to the lungs for oxygenation. The portion of the CO that is delivered to the lungs for oxygenation is "diluted" by the low O2 shunted blood

Gas exchange abnormalities due to dead space

In regions of dead space, because no gas exchange occurs, alveolar gas has the same composition as humidified inspired air: PAO2= 150mmHg, PACO2= 0mmHg

Gas exchange variability at each lung zone

In zone 1, where V/Q is highest, PaO2 is highest and PaCO2 is lowest. In zone 3, where V/Q is lowest, PaO2 is lowest and PaCO2 is highest.

Q5: Which of the following increase(s) hemoglobin P50: increased H+ concentration, increased pH, increased PCO2, increased 2,3-diphosphoglycerate (DPG) concentration?

Increased H+ concentration, increased Pco2, increased 2,3-diphosphoglycerate (DPG) concentration (Hint: Increased P50 = right shift.)

Defining characteristic of hypoxemia due to a right-to-left shunt

It CANNOT be corrected by having the person breathe a high O2 gas because the shunted blood never goes to the lungs to be oxygenated. The shunted blood will continue to dilute the normally oxygenated blood, and no matter how high the alveolar PO2, it cannot offset this dilution effect. However, this can be a useful diagnostic test.

Left-to-Right Shunts

Left-to-right shunts are more common and do not cause hypoxemia. Among the causes are PDA and traumatic injury. If blood is shunted from the left heart to the right heart, pulmonary blood flow (right heart cardiac output) becomes higher than systemic blood flow (left heart CO).

Response of muscle and joint receptors to exercise

Muscle and joint receptors send information to the medullary inspiratory center and participate in the coordinated response to exercise. These receptors are activated early in exercise, and the inspiratory center is commanded to increase the ventilation rate.

Q6: Which of the following decrease(s) the O2-binding capacity of hemoglobin: decreasing hemoglobin concentration, decreasing PaO2 to 60 mm Hg, increasing arterial Po2 to 120 mm Hg, left-shift of the O2-hemoglobin dissociation curve?

None of changes listed causes a change in O2-binding capacity of hemoglobin. (Hint: O2-binding capacity is the millileter of O2 bound to one gram of hemoglobin at 100% saturation. Right- and left-shifts change the percent saturation but do not alter the amount of O2 that can be bound at 100% saturation.)

Physiologic shunts

Normally, a small fraction of the pulmonary blood flow bypasses the alveoli. Examples include bronchial blood flow and the small amount of coronary (venous) blood flow that drains directly into the left ventricle through the thebesian veins and never perfuses the lungs. This means that PaO2 will always be slightly less than PAO2.

2,3 DPG with ascent to high altitude

One of the most interesting features of the body's adaptation to high altitudes is increased synthesis of 2,3 DPG by RBCs. The increased concentration of this molecule causes the O2Hb curve to shift to the right. This is associated with increased P50, decreased O2 affinity, and increased unloading of O2.

Consequence of left-to-right shunts

Oxygenated blood that has just retuned from the lungs is added directly to the right heart without being delivered to the systemic tissues. Since the right side of the heart normally receives mixed venous blood, the PO2 in blood on the right side of the heart will be elevated.

Summary of arterial and venous blood changes during exercise

PCO2 of mixed venous blood MUST increase because skeletal muscle is adding more CO2 than usual to venous blood. However, since the mean PaCO2 does not increase, the extra CO2 is expired by the lungs and never reaches systemic arterial pressure.

PO2 at high altitude

PO2= [380 - 47]mmHg x 0.21 PO2= 70mmHg

Q7: If ventilation/perfusion (V/Q)ratio of a lung region decreases, how will the Po2 and Pco2 in the blood in that region change?

Po2 is decreased and Pco2 is increased.

Advantages and disadvantages of polycythemia

Polycythemia is advantageous in terms of O2 transport to the tissues, but it is disadvantageous in terms of blood viscosity. The increased concentration of RBCs increases blood viscosity, which increases resistance (R) to blood flow (Q).

Prostacyclin (AKA prostaglandin I2)

Potent local vasodilator synthesized by endothelial cells

Regional variations in V and Q

Regional variations in ventilation are not as great as regional variations in blood flow. Therefore, the V/Q ratio is highest in zone 1 and lowest in zone 3, with the average for the entire lung being 0.8.

High V/Q

Regions of high V/Q have high ventilation relative to perfusion, usually because blood flow is decreased. Unlike dead space, which has NO perfusion, high V/Q regions have some blood flow.

Low V/Q

Regions with low V/Q have low ventilation relative to perfusion, usually because ventilation is decreased. Unlike shunts, which have NO ventilation, low V/Q regions have some ventilation

Changes of PaO2 and PaCO2 with exercise

Remarkably, mean values for arterial PO2 and PCO2 do not change during exercise. An increased ventilation rate and increased efficacy of gas exchange ensure that there is neither a decrease in arterial PO2 nor an increase in arterial PCO2 (The arterial pH may decrease, however, during strenuous exercise due to lactic acid).

Shunt (V/Q=0)

Right-to-left shunt is perfusion of lung regions that are not ventilated. It is illustrated by airway obstruction and right-to-left cardiac shunts

Barometric pressure at sea level and at high altitude

Sea level= 760mmHg At 18,000ft above sea level= 380mmHg

Right-to-Left Shunts

Shunting of blood from the right heart to the left heart can occur if there is a defect in the wall between the ventricles. As much as 50% of the CO can be routed from the RV directly to the LV and never be pumped to the lungs for arterialization.

Corrections needed to calculate the PO2 of humidified inspired air

Subtract the barometric pressure by the water vapor pressure (47mmHg), then multiply by the fractional concentration of O2, which is 21%

Summary of Zones

Summary: Zone 1 has the lowest blood flow and Zone 3 has the highest blood flow. Conversely, Zone 1 has the highest alveolar ventilation and zone 3 has the lowest alveolar ventilation

Changes in ventilation rate with high altitude

The most significant response to high altitude is hyperventilation. This allows for "extra" CO2 to be expired by the lungs and arterial PCO2 decreases, producing respiratory alkalosis. However, the decrease in PaCO2 and the resulting increase in pH will inhibit central/peripheral chemoreceptors and offset the increase in ventilation rate.

Major factor regulating pulmonary blood flow

The partial pressure of O2 in alveolar gas, PAO2. Decreases in PAO2 produce pulmonary vasoconstriction (i.e., hypoxic vasoconstriction).

Changes in the O2Hb dissociation curve during exercise

The curve shifts to the right due to increased tissue PCO2 (Bohr effect), decreased tissue pH, and increased temperature. This shift is advantageous since it increases the P50 and causes the affinity of hemoglobin to O2 to decrease, making it easier to unload O2

Hyperventilation and chemoreceptor response

The decrease in PaCO2 and increase in pH cause an increase in HCO3- excretion to occur after several days. This causes HCO3- to leave the CSF, and the pH of the CSF decreases toward normal. Thus, within a few more days, the offsetting effects are reduced and hyperventilation resumes.

What prevent actual closure of the capillaries in zone 1?

The fact that Pa is just high enough to prevent said closure, and thus zone 1 remains perfused, albeit at a low flow rate.

Zone 3

The gravitational effect has increased arterial and venous pressures, and both are now higher than alveolar pressure. Blood flow in zone 3 is driven by the difference between arterial and venous pressure. In zone 3, the greatest number of capillaries is open, and blood flow is the highest.

Acute Altitude Sickness

The initial phase of ascent to high altitude is associated with a constellation of complaints, including headache, fatigue, nausea, palpitations, and insomnia. All are attributable to the initial hypoxia and respiratory alkalosis, which abate when the adaptations are established.

Hypoxic vasoconstriction secondary to high altitude

The low PAO2 produces global vasoconstriction of pulmonary arterioles and an increase in pulmonary vasculature resistance. In response to this, pulmonary arterial pressure increases and with chronic hypoxia the RV hypertrophies as it must pump against an increased afterload.

Regional differences in PaO2 and PaCO2

The regional differences in V/Q produce regional differences in PaO2 and PaCO2, with the variability in PaO2 being much greater than regional differences in PaCO2

Disadvantage of high 2,3 DPG concentration

The right shift that results is disadvantageous to the lungs because it becomes more difficult to load the pulmonary capillary blood with O2.

Stimulus for polycythemia to occur

The stimulus for polycythemia is hypoxemia, which increases the synthesis of erythropoietin in the kidney. Erythropoietin acts on bone marrow to stimulate RBC production.

Thromboxane A2 and pulmonary blood flow

Thromboxane A2 is produced by macrophages, leukocytes, and endothelial cells in response to injury. It works as a potent local vasoconstrictor of both arterioles and veins.

Increase in PaCO2 due to right-to-left shunts

Usually, right-to-left shunts do not cause an appreciable increase in PaCO2. It changes minimally because the central chemoreceptors are very sensitive to changes in PaCO2 so that a small increase causes an increase in the ventilation rate, and the extra CO2 is expired.

Effect of gravity on pulmonary blood flow

When a person is upright, blood flow is lowest at the apex of the lung (zone 1) and highest at the base (zone 3). Gravitational effects increase pulmonary arterial hydrostatic pressure more at the base of the lung than at the apex.