Alveolar Stability and LaPlace's Law

Question 1

Five causes of hypoxemia

Answer 1

1. Low pressure of O_{2<strong> </strong>}in atmospheric air
2. Poor ventilation (thus locally low O₂ pressure)
3. Ventilation / perfusion mismatch
4. Shunt
5. Diffusion issue

Question 2

In which cases of hypoxemia is there appropriate arterial O₂ for the given alveolar O₂ gas?

Answer 2

Hypoventilation and low atmospheric O₂

Question 3

You can think of a shunt as . . .

Answer 3

. . . an extreme form of ventilation-perfusion mismatch

It is so bad that supplemental oxygen will not have any effect

Question 4

Shunt

Answer 4

When an alveolus is totally collapsed and has no volume to accept air. Cannot be treated with supplemental O₂, because there is no space anyway!

Question 5

Why doesn’t giving a patient with a shunt hypoxemia supplemental oxygen increase the oxygen content via the healthy, functioning, non-collapsed alveoli?

Answer 5

Remember that in a healthy alveolus, the blood comes out of the lung basically fully saturated. By giving supplemental O₂, you might increase the dissolved O₂, but not the hemoglobin-bound portion (which is most of the O₂ in arterial blood)

Question 6

Sub-groups of diffusion hypoxemia

Answer 6

1. Thickened membrane (inherently less permeable by gas)
2. Destroyed diffusion membrane or capillary

Question 7

Under normal, resting conditions, how much time does it take to saturate the blood with oxygen in a healthy alveolus?

Answer 7

Only 1/3 of the contact time between the alveolar gas and pulmonary capillary blood

So, even if there is a contact abnormality, it is unlikely to be a problem, since this process has a nice buffer time. When exercising, this may change, as blood goes through the lung faster.

Question 8

The resting position of an alveolus at 1 atm is. . .

Answer 8

. . . collapsed and empty

Question 9

The recoil forces of the lung can be characterized by. . .

Answer 9

. . . assigning a compliance. C = ΔV/ΔP

Another way to view this specifically for the lung, the lower the compliance of the lung, the greater the recoil forces are (either or both elastic and surface forces).

Question 10

Recoil forces of the lung

Answer 10

• Elastic force
• Surface tension

Question 11

Surface tension causes a liquid layer to . . .

Answer 11

Surface tension causes a liquid layer to shrink to form the smallest possible surface area.

Question 12

Surfactant properties

Answer 12

Dipalmitoylphosphatidyl choline

Has the lowest surface tension of any biological substance ever measured. Unlike most detergents, which have a constant effect on surface tension regardless of the area of the surface, surfactant’s effect is 1) variable at different surface areas and is 2) dependent upon the direction in which the surface area is changing, i.e., whether it is getting bigger or smaller

Question 13

Hysteresis

Answer 13

The separation of the inflation and deflation limbs of the pressure-volume curves of the lung. Hysteresis is an empirical phenomenon, and mechanisms are only proposed.

Occurs only when the lung is filled with air, as it is related to properties of liquid-air interfaces.

Question 14

When the lung is filled with liquid, the work expended to distend the lung is necessary to overcome ___. When the lung is filled with air, one must overcome ___.

Answer 14

When the lung is filled with liquid, the work expended to distend the lung is necessary to overcome only elastic forces. When the lung is filled with air, one must overcome both elastic forces and surface tension forces.

Question 15

Surfactant during lung inflation

Answer 15

During lung inflation, the liquid lining the alveolar surface expands and the density of surfactant in the surface layer decreases. Molecules of surfactant residing in micelles in the deflated state and are pulled out and dispersed across the surface to reduce tension.

The slope of the inspiratory curve increases, which indicates that compliance is increasing. Once the lung inflates enough, there are not enough micelles to continue this effect and so the compliance is determined increasingly by increasing surface forces and elastic forces.

Question 16

Surfactant during lung deflation

Answer 16

Initially, as surface area decreases in the first phase of deflation of the lung. The liquid lining layer is compressed and the density of the surfactant molecules increases. Pressure and tension are going down to the same degree with small changes in volume (or radius per La Place’s Law). Compliance is quite high.

During the second phase of deflation, the molecules of surfactant are leaving the surface layer at about the same pace as surface area is decreasing. So, density of the surfactant is constant and thereby slope of the deflation curve (compliance) is constant.

At the lowest lung volumes, surfactant density decreases further, surface tension increases, and there is a greater tendency for alveoli to collapse.

Question 17

You cannot calculate the “compliance” of the lung during deflation by . . .

Answer 17

You cannot calculate the “compliance” of the lung during deflation by looking solely at the slope of the pressure-volume curve

Compliance is a concept that describes the characteristics of a flexible structure when one tries to inflate it; when a structure’s recoil forces are increased, compliance goes down and the slope of the curve diminishes. In contrast during exhalation, when recoil forces are increased, deflation occurs more quickly, the slope of the deflation curve is steeper.

Question 18

Where do the surfactant micelles come from between expiration and inspiration?

Answer 18

From a combination of the subsurface micelles and newly produced surfactant, re-entering the surface layer.

Because the surfactant entering the surface layer during inspiration must be drawn, at least in part, from newly produced molecules, the density of surfactant in the surface layer during inspiration is not as great as during expiration.

Consequently, for a given lung volume, surface tension is greater during inspiration than during expiration

Question 19

Role of surfactant during inspiration vs expiration

Answer 19

Surfactant increases pulmonary compliance (less pressure needed to achieve a given lung volume during inspiration) and helps prevent alveolar collapse during expiration (i.e., stabilizes alveoli during exhalation).

Question 20

Surfactant’s role in regulating edema

Answer 20

A third effect of surfactant is that it minimizes the transudation of fluid from the pulmonary capillaries into the alveoli.

Surface tension tends to “suck” fluid from the capillaries lining the alveoli into the alveolar space (the surface tension reduces the hydrostatic pressure in the tissue around the capillaries). By reducing these surface forces, surfactant prevents transudation of fluid.

This is a form of non-cardiogenic pulmonary edema

Question 21

Bohr Effect

Answer 21

Shift of the curve to the right with greater concentration of hydrogen ions in the blood, i.e., lower pH. The association of hemoglobin with hydrogen ions lowers the affinity of hemoglobin for oxygen. This allows the hemoglobin to release more oxygen to tissues that are not getting sufficient oxygen and are consequently relying upon anaerobic metabolism

Question 22

Factors shift the hemoglobin-O₂ binding curve

Answer 22

temperature, PCO2, pH, and 2,3 diphosphoglycerate (DPG)

Question 23

Hb-O₂ binding curve

Answer 23

Question 24

The Hb-O₂ curve is almost fully saturated until the ppO₂ drops below. . .

Answer 24

. . . about ~60 mmHg.

Remember that room air has a pressure of approximately 150 mmHg, that the alveolus is closer to ~104 mmHg, and that normal arterial blood has about ~95-100 mmHg.

Question 25

ppO₂ in venous blood

Answer 25

~40-50 mmHg

Question 26

Distribution of blood flow in the lungs

Answer 26

Greater at the base of the lungs than at the apex. This is probably due in part to branching patters of the pulmonary vessels and possibly in part to the effect of gravity on pulmonary flow.

Question 27

Ventilation in the lung is greater at. . .

Answer 27

. . .the base than at the apex, probably in part to differences in pleural pressure.

More positive pleural pressure (due to the weight of the thorax on the base of the lung) leads to a smaller lung volume at the end of exhalation, which leads to a lower volume for the lung units in that region. Thus, this region of the lung is operating at a more compliant portion of its pressure-volume relationship

Question 28

Alveolar hypoxia leads to. . .

Answer 28

Alveolar hypoxia leads to constriction of pulmonary arterioles leading to that alveolus (probably mediated via nitric oxide metabolism); this leads to redirection of blood flow to alveoli receiving better ventilation.

Question 29

V/Q mismatch-induced hypoxemia only occurs when. . .

Answer 29

. . . there is alveolar pathology and there is a problem with alveolar vasoconstriction, preventing the adaptive vasoconstriction of vessels supplying collapsed alveoli.

Question 30

Alveolar Gas Equation

Answer 30

The difference between the PAO₂ and the PaO₂ (written typically as: A-aDO₂ or the alveolar to arterial oxygen difference) defines whether there is a gas exchange problem, i.e., whether the cause of hypoxemia is due to issues at the level of the alveolus and/or pulmonary capillary.
PAO₂ = fO₂ (P_atm - P_water) - PCO₂ / R

R = respiratory quotient

Question 31

Normal A-aDO₂

Answer 31

Normal A-aDO2 < age (0.3)

As healthy people age, we lose some of the elastic recoil of the lungs, which can lead to areas of V/Q mismatch

Question 32

Even in completely normal individuals, ventilation and perfusion . . .

Answer 32

even in completely normal individuals, ventilation and perfusion are not perfectly matched​

Hence why A-aDO₂ is greater than zero even in young, healthy individuals

Question 33

The drop in alveolar oxygen should equal . . .

Answer 33

The drop in alveolar oxygen should equal the rise in alveolar carbon dioxide

Question 34

Hypoventilation leads to . . .

Answer 34

Hypoventilation leads to hypercapnia and to hypoxemia

Question 35

Drugs that suppress ventilation

Answer 35

sedative or narcotic drug overdose

Question 36

respiratory quotient

Answer 36

The ratio of carbon dioxide molecules produced to oxygen molecules consumed;

Eating a typical American diet, R=0.8. This value increases toward 1.0 with greater proportion of intake comprising carbohydrates and it decreases (toward 0.6-0.7) if one is eating and metabolizing primarily fat.

Question 37

Effects of increased ventilation on blood oxygen

Answer 37

Not much. At least not for a resting individual.

Remember that arterial hemoglobin is basically getting saturated at baseline in a healthy individual, so more ventilation is only really going to get rid of more CO₂.

Question 38

Oxygen content in the blood

Answer 38

O₂ content = Amount O₂ Bound to Hgb + Amount O₂ Dissolved in Blood

O₂ content = 1.35 (Hgb)(Oxygen saturation) + 0.003(PaO₂)

Question 39

Each gram of hemoglobin can combine with approximately ___ mL of oxygen.

Answer 39

Each gram of hemoglobin can combine with approximately 1.35 mL of oxygen.

Question 40

Supplemental oxygen can help with. . .

Supplemental oxygen can’t help with. . .

Answer 40

Supplemental oxygen can help with hypoxemia of V/Q mismatch and hypoventilation.

Supplemental oxygen can’t help with hypercapnia caused by V/Q mismatch. In fact, it may worsen it. by increasing alveolar O2 in poorly ventilated units, you will reduce their vasoconstriction. Now sent once again to poorly ventilated regions of lung, and consequently the body is less able to eliminate carbon dioxide when hypoxic pulmonary vasoconstriction is reversed and perfusion to poorly ventilated lung units is increased.

Question 41

Intra-Pulmonary shunt

Answer 41

extreme form of V • /Q mismatch in which there is perfusion to alveoli, but no ventilation (i.e., V • = 0).

Question 42

The most classic form of shunt

Answer 42

blood goes from the right side of the heart to the left side of the heart without ever passing through pulmonary capillaries, e.g., an arterio-venous malformation (AVM)

Caused by either an abnormal connection between pulmonary arterioles and venules, or a patent foramen ovale (PFO)

Question 43

Things that may cause an intra-pulmonary shunt

Answer 43

• Collapsed alveoli
• Alveoli filled with fluid
• Alveoli filled with inflammatory cells

Question 44

“clinically significant” shunt

Answer 44

If that patient is hypoxemic and supplemental oxygen does not raise the PaO₂ substantially (the amount considered “substantial” depends on the concentration of oxygen administered)

Question 45

Approach to hypoxemia

Answer 45

1. Start with the arterial blood gas, and calculate the alveolar to arterial oxygen difference (A-aDO2)
   
   1. If normal, hypoxemia is due either to reduced FIO2 or alveolar hypoventilation. If paCO2 is also elevated, hypoventilation is the cause.
   2. If the A-aDO2 is abnormal (greater than 0.3 X age), you are dealing with V/Q mismatch or shunt
   3. If the patient has a drop in PaO2 or O2 saturation with activity, a diffusion abnormality is present

Question 46

Characteristics of surfactant deficiency

Answer 46

Question 47

___ is characterized by an increase in the alveolar-arterial oxygen difference

Answer 47

V/Q mismatch is characterized by an increase in the alveolar-arterial oxygen difference

Question 48

In cardiogenic pulmonary edema, the fluid is ____. In inflammatory pulmonary edema, the fluid is ____.

Answer 48

In cardiogenic pulmonary edema, the fluid is protein-free. In inflammatory pulmonary edema, the fluid is protein-rich.

Question 49

Ultimately, ___ is what causes cardiogenic pulmonary edema.

Answer 49

Ultimately, high hydrostatic pressure in the pulmonary capillaries is what causes cardiogenic pulmonary edema.

Question 50

Clinical definition of hypoventilation

Answer 50

High paCO₂

Question 51

Diffusion abnormalities are only ever an issue ___.

Answer 51

Diffusion abnormalities are only ever an issue during exercise.

Question 52

In reality, hypoxemia is almost always caused by ____.

Answer 52

In reality, hypoxemia is almost always caused by V/Q mismatch, often with an additional issue.

Question 53

Lungs filled with edematous fluid are ___ compliant,

Answer 53

Lungs filled with edematous fluid are MUCH less compliant,

first because of the fluid itself, second because (if the fluid is plasma with protein) it intereferes with surfactant.

Question 54

If a patient aspirates vomit or has a lung infection, you would expect ___ to increase.

Answer 54

If a patient aspirates vomit or has a lung infection, you would expect A-aDO₂ to increase.