Ventilation/Perfusion Balance and Hypoxemia

4 Causes of Hypoxemia**

#3 is rarest (complete R→L shunt) #4 is most important/common -Chronic low grade V/Q mismatch is impossible to differentiate from diffusion impairment. More often than not, diffusion impairment is the cause of V/Q mismatch. SO, if you see a question where V/Q mismatch and diffusion impairment are both choices, choose V/Q mismatch because it is more clinically relevant.

Mechanisms of Hypoxia

1. Stagnant Hypoxia 2. Anemic Hypoxia 3. Histotoxic Hypoxia

Mechanism Behind Cheyne-Stokes Breathing

1.1. occurs in CHF His explanation confused me so I erased what I had written. I hope you can understand it a little better & then explain it to me.

Treatment of Altitude Sickness

100% oxygen

Treatment of Diffusion Impairment

100% oxygen A-a gradient will also return to normal due to such a large increase in ∆P If you increase to 100% oxygen PAO₂ will be ~670 mm Hg, therefore PaO₂ will be ~660 mm Hg! -He harped on this

What is diagnostic of a Right-to-Left shunt?

A-a gradient that is not only non-responsive to 100% O₂, but *widened!* V/Q ratio of zero [Patient will also have hypocapnia due to reflex stimulation of peripheral chemoreceptors by decreased PaO₂.]

Blood Flow in the Lungs

Also varies (why? PATCH) so that blood flow is greatest at the base.

Diseases where there is Non-Uniform Resistance to Airflow (Variable Airway Obstruction)

Bronchoconstriction (e.g. Asthma) Airway inflammation (e.g. Bronchitis) Mucus obstruction (e.g. Chronic bronchitis, CF, Bronchiectasis) Airway compression (e.g. Tumors, emphysema)

High V/Q Mismatch

Caused by a large Pulmonary Embolus V/Q of ∞ is dead space ventilation.

Diagnostic Criteria for a V/Q Mismatch

Compensatory hyperventilation = lower PaCO₂

What happens when V/Q is decreased? How is decreased?

As you decrease V/Q ratio below 0.8, the PaO₂ & PaCO₂ move towards the O₂ and CO₂ partial pressures of mixed venous blood. i.e. lowest possible O₂ and highest possible CO₂. V/Q can be decreased by hypoventilation → ventilating less than perfusing

What happens when V/Q is increased? How is it increased?

As you increase V/Q ratio above 0.8, the PaO₂ & PaCO₂ move towards the PIO₂ and PICO₂ (0) i.e. highest possible O₂ and lowest possible CO₂. V/Q can be increased by increasing ventilation (hyperventilation) → ventilating in excess of perfusion

The word "ventilation"

Assume it means Alveolar Ventilation, which means you have to subtract the Dead Space Ventilation (unless it's staid that it's Total Ventilation).

Hypercapnia

Basically every lung disease we will see will lead to hypoxemia, which may or may not be accompanied by hypercapnia (elevated PaCO₂). Hypercapnia should not be used to diagnose lung disease because it is frequently masked by compensatory hyperventilation. However, when present, hypercapnia is diagnostic.

Anemic Hypoxia - Definition, Causes

DEFINITION: Hypoxia due to decreased % O₂ sat. CAUSES (Reduced [Hb]): Anemia CAUSES (Normal [Hb]): 1. *Methemoglobinemia*, which is oxidation of iron in Hb from the ferrous (Fe²⁺) to ferric (Fe³⁺) state. It can be congenital (HbM), due to nitrite poisoning, or a toxic reaction to oxidant drugs. 2. *Carbon Monoxide Poisoning*: Hb has 240x greater affinity for CO than O₂. As a result, % sat in arterial blood & thus total oxygen content of the blood are reduced in the presence of CO.

Stagnant Hypoxia - Definition, Causes

DEFINITION: Reduced oxygen delivery to the tissues due to decreased blood flow. -PaO₂, [Hb], % O₂ sat, and arterial oxygen content are all normal -O₂ extraction (a-v O₂) increases to compensate for reduced delivery CAUSES: 1. Local ischemia 2. Systemic due to decreased cardiac output (e.g. CHF)

Histotoxic Hypoxia - Defintiion, Causes

DEFINITION: The total oxygen content is normal, but for some reason the tissues cannot use the oxygen being provided. CAUSES: 1. Cyanide Poisoning - binds to & inhibits cytochrome oxidase, blocking oxidative phosphorylation 2. Carbon Monoxide Poisoning - inhibits oxidative phosphorylation 3. Primary mitochondrial respiratory chain disease

What is the most common V/Q ratio of people with lung pathology? (Increased or Decreased)

Decreased in 95% of patients with lung disease!!

Diseases where there is Non-Uniform Lung Compliance

Emphysema (degraded elastic fibers) Fibrosis (e.g. IPF, pneumoconioses, ARDs, Collagen diseases) Inadequate surfactant production (e.g. ARDS) Pulmonary vascular congestion (e.g. interstitial edema) Parenchyma compression (e.g. tumors)

Hypoxemia fixed by 100% oxygen vs. Hypoxemia not fixed by 100% oxygen

Fixed by 100% O₂ = Low V/Q Ratio (V/Q mismatch) Not fixed by 100% O₂ = V/Q Zero (Right-to-Left Shunt) BOTH will have widened A-a Gradient.

Treatment of Hypoventilation

Give 100% oxygen

Global Diffusion Impairment

Global = both lungs & all lobes involved Reduced SA or increased thickness will cause diffusion impairment. There will be enough oxygen in the alveoli, but it won't be able to get across. Not present at rest, because of the spare time for gas diffusion in the pulmonary capillaries. Hypoxemia from diffusion impairment occurs in exercise. Read pic for details.

Effect of Hypoventilation on Pulmonary Gas Exchange

Hypoventilation = not breathing enough → Increased PACO₂ → Leads to Hypercapnia → Hypoxemia First calculate change in PACO₂!

A-a Gradient: Normal vs. Hypoventilation

In Hypoventilation A-a gradient will still be normal! It only changes if there is a problem with diffusion.

Mechanism of Large Pulmonary Embolus and High V/Q Mismatch

In Pulmonary Embolism Hypoxemia is not a concern, Hypercapnia is. If you see Hypercapnia 1st thing that should come to mind is Hypoventilation, 2nd is Pulmonary Embolism. Cardiac output is redirected to the good lung. The good lung is hypoventilating beacuse the V is the same but the Q is doubled. This results in ↑PaCO₂, which causes PaO₂ to decrease → Severe Acidosis. This is only true for *large* pulmonary emboli.

Effect of Gravity on Ventilation

In the lungs, the V/Q ratio is non-uniform (0.8 is an average). We have assumed that PIP is uniform around the lungs, but it's actually not because of the effects of gravity. Due to gravity, PIP Is less negative at the base, and more negative at the apex. The more negative the PIP, the greater the resting volume of the lungs. The more the volume in the lungs, the greater the elastic recoil, so it's difficult to inflate the apex and easy to inflate the base. This results in the lungs being over-inflated at the base and under-inflated at the apex. So, when you breathe in, ventilation goes primarily toward the base as opposed to the apex. BOTTOM LINE: Ventilation goes more towards the base and less towards the apex.

SUMMARY: For Hypoventilation, Diffusion Impairment, Low V/Q & R→L Shunt what is: PaO, mixed P, and A-a on room air and PaO and A-a on 100% O₂?***

KNOW THIS CHART (Note that I changed the farthest box to the right in the Low V/Q row from N to ↑- error on his slide)

The left lung is fully obstructed & not getting any airflow, but the right lung is getting normal airflow. What happens to PaO₂, Hb saturation and arterial oxygen content in each lung?

LEFT LUNG: Blood coming out is mixed venous blood → PaO₂ = 40 mm Hg → Hb Saturation is 75%. Total arterial oxygen content coming out is 15 ml/dl. RIGHT LUNG: PaO₂ = 100 mm Hg. The total arterial content of oxygen coming out is 20 ml/dl.

What is the maximum possible PaO₂ & PaCO₂ if you're breathing room air? Minimum?

Max PaO₂: 150 mm Hg (inspired air) Min PaO₂: 40 mm Hg (its coming in the mixed venous blood) Max PaCO₂? 47 mm Hg Min PaCO₂? 0 mm Hg At normal V/Q Ratio (0.8), PaO₂ is 100 mm Hg and PaCO₂ is 40 mm Hg.

V/Q Mismatch with Low V/Q Areas - Definition & Causes

Means V/Q <0.8 but >0 Expected PaO₂ is closer to mixed venous blood (PaO₂ <100 mm Hg, PaCO₂ >40 mm Hg) Every lung disease that is not global will lead to a V/Q < 0.8 CAUSES: 1. Non-uniform resistance to airflow, i.e. variable airway obstruction 2. Non-uniform lung compliance

What happens if you give this patient 100% oxygen? What is the A-a gradient after the oxygen?

No effect on the unventilated lung. It will increase the PaO₂ in the blood coming from the ventilated lung (650 mm Hg). However, this doesn't help, because Hb saturation is still 100%. When you mix the blood, you have an arterial oxygen content of 18 ml/dl, which is a HbO₂ saturation of 88% → PaO₂ = 55 mm Hg. What is the A-a gradient? 650 - 50 = 600 mm Hg!!

Will CO poisoning cause hypoxemia? Hypoxia?

No!! PaO₂ is unchanged! But it will cause Hypoxia!!

Ventilation/Perfusion (V/Q) Matching - Normal Value

Normal Ventilation = 4.2 L/min Normal Perfusion = 5.0 L/min *Normal V/Q = 4.2/5 = 0.8* This is the optimal Ventilation/Perfusion ratio.

Hypoxemia due to High Altitude

Note that barometric pressure is reduced from 760 to 429 mm Hg You will have hypoxemia but NOT hypercapnia. This is because you will compensate for reduced oxygen by hyperventilating.

Net Effects of Hypoventilation on Gas Exchange (aka Clinical Clues), Causes & Other Name

Other Name: Hypercapnic/Hypoxemic Respiratory Failure CLINICAL CLUES: Hypercapnia (↑ PaCO₂) + Hypoxemia (↓ PaO₂) + Normal A-a Gradient → Hypoventilation! -There can't be a compensatory increase in ventilation because that's the problem in the first place. CAUSES: Drug-induced (heroin, sedatives, hypnotics, anesthesia) Myasthenia gravis Neuromuscular Failure

Hypoxia - Defintion

O₂ deficiency at the level of the tissues May or may not be accompanied by hypoxemia

Hypoxemia - Definition

Reduced PaO₂ Can lead to hypoxia.

Puri Add in at beginning of next lecture:

Restrictive pulmonary disease has a greater chance of looking like a diffusion impairment COPD has a greater chance of looking like a low V/Q

Normal Alveolar-arterial (A-a) Gradient

So far, we've said that PAO₂ is 100 mm Hg and PaO₂ is also 100 mm Hg. This is false. *Normal A-a gradient <10 mm Hg* (this varies among texts) PaO₂ is normally lower than PAO₂, but this is not because of any type of problem. It's because up to 3% of blood flow coming to the lungs bypasses the alveoli. This is the blood that goes to the Anatomical Dead Space (i.e. bronchial & pleural veins) never gets oxygenated, reducing PaO₂ concentration. Therefore, normal PaO₂ is actually 90 mm Hg.

Right-to-Left Shunting - Physiologic

The alveolus is getting blood flow but is not getting ventilated. V/Q = 0 If V/Q = 0, expected PaO₂ is 40 mm Hg (same as mixed venous blood).

What happens when the blood from each lung mixes together? What is the A-a gradient?

When they mix, blood of 15 ml/dl combines with blood of 20 ml/dl. The combined oxygen content is 17.5 ml/dl. At 17.5 ml/dl arterial oxygen content, hemoglobin saturation is 88% (use O₂ content equation). Looking at Hb-O₂ dissociation curve, at 88% HbO₂ saturation, PaO₂ = 55 mm Hg → Severe hypoxemia Remember, PAO₂ = 100 mm Hg → Huge A-a gradient (50 mm Hg)

Net Effect of Diffusion Impairment on Gas Exchange w/Hypoxemia

There will not be hypercapnia because there will be compensatory hyperventilation (in fact, it will be reduced). -However, if there is chronic diffusion impairment, the patient will have hypercapnia (slow buildup of CO₂) A-a gradient is increased!

Cheyne-Stokes Breathing

Usually found in CHF or brain damage. In normal breathing, you inspire & expire to the same depth. In Cheyne-Stokes breathing you have progressive increasing depth of respiration that reaches a peak and then progressively decreases, followed by an abrupt stop to breathing for some time. Then it repeats.

What happens when V/Q increases or decreases?***

V/Q at the apex is highest, so the blood coming out from that area has a PaO₂ closer to inspired air (>100 mm Hg). -*I*ncreased V/Q = *I*nspired air V/Q at the base is lowest, so the blood coming out from that area has a PaO₂ closer to mixed venous blood (<100 mm Hg).

Measurement of the Physiological Dead Space

Vd = Dead space volume Vt = total ventilation *This is not on Puri's exam* but we need to know it for boards

Right-to-Left Shunting - Anatomic

Venous blood mixes with arterial blood through abnormal anatomical connections

Regional Distribution of V/Q***

Ventilation and blood flow are greatest at the base, thus V/Q ratio is lowest at the base (this is because the increased blood flow > increased ventilation) and highest at the apex. V/Q = 0.8 in the mid portions of the lungs

What happens to the pressures and Hb saturation in these situations? How does it compare to complete obstruction of a lung?

Will result in the same exact situation as when one lung was obstructed. Under-ventilated region of the lung results in venous blood that mixes with arterial blood (from well ventilated region), resulting in Hb sat of 88% and a PaO₂ of ≈ 55 mm Hg. HOWEVER, they *do have a partial response to 100% oxygen*. This is because the diseased region of the lung is not unventilated, it's under-ventilated. PaO₂ in the healthy area will increase to 650 and PaO₂ in the under-ventilated portion will increase significantly (e.g. 200 mm Hg), though not to 650 mm Hg. With a PaO₂ of 200 mm Hg, Hb saturation will be 100%. The *A-a Gradient will remain wide* (650-350 = 300 mm Hg). In this case, the dissolved oxygen is 1 (in bad area) and 2 (in healthy area), resulting in dissolved O₂ of 1.5 → 350 mm Hg .Basically, I think the dissolved O₂ has more of an effect here than on the total blockage situation so that helps a little in lessening the A-a gradient, but really I think it doesn't make much difference and just confused everything. Actually, he kept talking and now I don't get it at all.

Will COPD cause hypoxemia? Hypoxia?

Yes, both!