https://lifeinthefastlane.com/ccc/a-a-gradient/

A-a gradient

OVERVIEW

• calculated as PAO2 – PaO2
• PAO2 is the ‘ideal’ compartment alveolar PO2 determined from the alveolar gas equation
• PAO2 = PiO2 – PaCO2/0.8
• A normal A–a gradient for a young adult non-smoker breathing air, is between 5–10 mmHg.
• However, the A–a gradient increases with age (see limitations)

CLASSIFICATION OF HYPOXIA BASED ON A-a GRADIENT

Normal A-a gradient

1. Alveolar hypoventilation (elevated PACO2)
2. Low PiO2 (FiO2 < 0.21 or barometric pressure < 760mmHg)

Raised A-a gradient

1. Diffusion defect (rare)
2. V/Q mismatch
3. Right-to-Left shunt (intrapulmonary or cardiac)
4. Increased O2 extraction (CaO2-CvO2)

LIMITATIONS

• Gradient varies with age and FiO2:

FiO2 0.21 – 7 mmHg in young, 14 mmHg in elderly
FiO2 1.0 – 31 mmHg in young, 56 mmHg in elderly

•  For every decade a person has lived, their A–a gradient is expected to increase by 1 mmHg – a conservative estimate of normal A–a gradient is < [age in years/4] + 4.
• an exaggerated FiO2 dependence in intrapulmonary shunt (PAO2 vs PAO2/PaO2 difference diagram with regard to increasing percentage of shunt) and even more so in V/Q mismatch.

Pulmonary Diffusing Capacity

Khan video on diffusion

This is a good video but does not mentioned the influence of capillary volume and hemoglobin.

Capillary volume is part of the surface area component (alveolar surface area + capillary volume) of the Fick Equation and is influenced by factors such as exercise which increases diffusing capacity by increasing blood flow to the top of the lungs and thereby increasing capillary volume = surface area for diffusion.  The Fick equation may be simplified by combining (A x K)/T into a single parameter, DL, the diffusing capacity of the lung.

Passive diffusion proceeds at a rate proportional to the driving force (P1 – P2), surface area (A), and solubility of the diffusing gas (K) and inversely proportional to thickness of the barrier (T).  These factors comprise Fick’s law for passive diffusion, where K is Krogh’s diffusion constant. Because it is not possible to accurately measure area or thickness, these membrane properties along with K are lumped to form a parameter called diffusing capacity, DL.  As shown in the figure, the flow of gas by diffusion, in ml/min, = DL (P1 – P2).  Note that when P1 = P2, the driving pressure becomes zero and gas movement stops. This equation for gas flow can be rearranged to provide the equation for diffusing capacity:  DL = Vgas / (P1 – P2)

Hemoglobin concentration is important in the rate of diffusion because the final step in diffusion of oxygen is reaction with hemoglobin. In fact, the reaction rate of with hemoglobin accounts for about half of the total resistance to oxygen uptake in the lungs.  This means that anemia can result in impaired diffusion.
Also, as described below, diffusing capacity is measured using carbon monoxide. The binding of CO to Hb goes faster with more Hb; e.g., anemia will reduced the measured diffusing capacity.

How is Diffusing Capacity Measured?

Carbon monoxide is used to measure diffusing capacity of the lung (DL).  Advantages of CO are that its uptake is limited by membrane properties (diffusion limited) and not by blood flow (perfusion limited).  This is so because CO gas binds 100% with hemoglobin meaning there is no back pressure (P2) to slow or stop diffusion.  Since P1 is kept constant, the rate of transfer depends only on DL.

https://www.openanesthesia.org/pulm-diffusing-capacity/

Pulmonary diffusing capacity is often measured by Diffusion capacity of the Lungs for carbon monoxide (DLCO). In essence, this measures how much CO can pass from the alveoli to the blood in the pulmonary capillaries, thus giving clinicians the broader idea of how much inhaled gas can pass into the blood through the lungs. 

While some state the “DLCO correlates with the total functioning surface area of the alveolar-capillary interface (Butterworth, et al),” Dr. McCormack notes, “Older textbooks suggest that thickening of the alveolar-capillary membrane (in interstitial lung disease) and loss of alveolar membrane surface area (in emphysema) are the primary causes of a low DLCO. However, subsequent experimental data suggest these and most other diseases that influence the DLCO do so by reducing the volume of red blood cells in the pulmonary capillaries” (McCormack). Regardless of theory, whether the surface area or the alveolar surface itself is modified or the volume of the blood in the pulmonary capillaries is modified, the DLCO reflects how much gas can be transferred to the blood via the lungs.

1. Butterworth IV, JF, Mackey DC, Wasnick JD.  Morgan & Mikhail’s Clinical Anesthesiology, 5th ed. New York, NY: McGraw Hill; 2013.

1. McCormack, Meredith. “Diffusing Capacity for Carbon Monoxide.” Ed. James Stoller and Helen Hollingsworth. N.p., 14 Apr. 2015. Web.

New Job in Grenada/England

Arrived in Grenada😏

View from our hotel room

SGU campus is across the harbor

Life of a Medical Student in Grenada

First Without Oxygen

"I am nothing more than a single narrow gasping lung, floating over the mists and summits." Reinhold Messner, Everest

Climbing Mount Everest, the tallest mountain in the world, was a challenge that eluded scores of great mountaineers until 1953, when Sir Edmund Hillary and Tenzig Norgay first reached its summit. Over the next three decades, more "firsts" followed, including the first ascent by a woman, the first solo ascent, the first traverse (up one side of the mountain and down the other) and the first descent on skis. But all of these climbers had relied on bottled oxygen to achieve their high-altitude feats. Could Mt. Everest be conquered without it?

As early as the 1920s, mountain climbers debated the pros and cons of artificial aids. One, George Leigh Mallory, argued "that the climber does best to rely on his natural abilities, which warn him whether he is overstepping the bounds of his strength. With artificial aids, he exposes himself to the possibility of sudden collapse if the apparatus fails." The philosophy that nothing should come between a climber and his mountain continued to have adherents fifty years later. 

In the 1970s, two of its strongest proponents were Reinhold Messner and Peter Habeler. Messner had achieved considerable notoriety by completing a series of spectacular Alpine rock climbs without the use of metal protection pegs. In 1974, Messner teamed up with Habeler, a quiet Mayrhofen guide who shared his philosophy, and the pair proceeded to take the climbing world by storm. Agile and slight of build, they scaled the Matterhorn and Eigerwand faces in record time. In 1975, they made a remarkable ascent of the 11^th highest mountain in the world, Gasherbrum, without using supplemental oxygen. By 1978, they had set their sights on climbing Mt. Everest—without bottled oxygen.

Messner and Habeler quickly found themselves the subject of criticism by members of both the climbing and medical communities. They were labeled "lunatics," who were placing themselves at risk for severe brain damage. The physiological demands of climbing Everest had been studied on previous expeditions, and found to be extreme; in 1960-61, tests conducted on members of an expedition led by Sir Edmund Hillary concluded that oxygen levels at the summit of Mt. Everest were only enough to support a body at rest—and that the oxygen demands of a climber in motion would certainly be too great.

Despite the controversy, Messner and Habeler continued with their plan. They would climb together with the members of the Austrian Everest Expedition into the Western Cwm, and then make their own separate attempt for the summit. The teams arrived at Base Camp in March of 1978 and spent the next few weeks establishing a secure route through the Icefall, erecting camps I-V and preparing for their ascent. 

Messner and Habeler's first attempt began on April 21. They reached Camp III on the Lhotse Face on April 23. That night, Habeler became violently ill with food poisoning from a can of sardines. Messner decided to continue his ascent, without his debilitated partner, and set off with two Sherpas the next morning. Upon reaching the South Col, the three climbers were suddenly trapped in a violent storm. They battled temperatures of -40 degrees Fahrenheit and winds of 125 m.p.h. for two full days. Exhausted from struggling with a torn tent and severe hunger, even Messner later admitted to believing his venture was "impossible and senseless." Finally, a break in the weather enabled the shaken party to descend to Base Camp and recuperate.




http://www.pbs.org/wgbh/nova/everest/history/firstwoo2.html


Messner and Habeler discussed making one more bid for the summit. Habeler had begun to reconsider the use of oxygen, but Messner remained steadfast, declaring that he would not use oxygen—nor climb with anyone who was using it. He believed that climbing as high as possible, without oxygen, was more important than reaching the summit. Habeler, unable to recruit a new partner, relented, and the two became a team once more.

On May 6, Messner and Habeler set out again. They reached Camp III (7200 meters) easily and, despite a new blanket of heavy snow, felt ready to move on to the South Col the next day. They were now reaching altitudes where they could expect to feel the effects of oxygen deprivation. Messner and Habeler had agreed on carrying two oxygen cylinders to Camp IV, in case of an emergency, and had also made a pact to turn back if either person lost his coordination or speech. 

The next day, it took them only three and a half hours to reach the South Col (7986 meters), where they camped for the afternoon and evening. Habeler complained of a headache and double vision on the climb up, but felt better after resting, even though both men frequently woke up from their naps gasping for air. They forced themselves to drink tea, hoping rehydration would lessen the effect of the thin air. 

At 3 am on May 8, the two woke and began preparing for the day's attempt on the summit. Simply getting dressed took them two hours. The weather was questionable, but they decided to break camp. Since every breath was now precious, the pair began using hand signals to communicate. Progress was slow. Trekking through the deep snow was exhausting, so they were forced to climb the more challenging rock ridges. It took them four hours to reach Camp V (8500 meters), where they rested for thirty minutes. Even though the weather was still threatening, they decided to continue—at least to the South Summit, which was 260 vertical meters away. 

Messner and Habeler now faced exhaustion unlike any they'd encountered before. Every few steps, they leaned on their ice axes and gasped for breath. Messner described feeling as though he were going to "burst apart." As they climbed higher, they fell to their knees and even lay down in an effort to recover their breath. 

Upon reaching the South Summit, the pair roped themselves together and pressed on. The wind battered them about, but they saw a break in the sky and were hopeful that the weather would improve. They had 88.12 vertical meters to go. Messner described a feeling of apathy mingled with defiance. They reached the Hillary step and continued, alternating leads and resting three or four times. At 8800 meters they were no longer roped together, but were so affected by the lack of oxygen that they collapsed every 10 to 15 feet and lay in the snow. Messner testified into his tape recorder that, "breathing becomes such a serious business we scarcely have strength to go on." He described feeling like his mind was dead—and that it was only his soul that compelled him to crawl forward.

Sometime between 1 and 2 in the afternoon on May 8, 1978, Messner and Habeler achieved what was believed to be impossible—the first ascent of Mt. Everest without oxygen. Messner described his feeling: "In my state of spiritual abstraction, I no longer belong to myself and to my eyesight. I am nothing more than a single narrow gasping lung, floating over the mists and summits." 

It took Habeler an hour to get down to the South Col, and Messner an hour and three quarters—for a distance that had taken them eight hours that very morning. They reached Base Camp, jubilant, two days later.

Messner and Habeler's success puzzled the medical community, and caused a re-evaluation of high-altitude physiology. Messner would return to Mt. Everest in 1980 to successfully complete a solo ascent—again without supplemental oxygen. 

Thanks to my students at UTRGV School of Medicine

We made it to New Mexico!

Thank You

Class of 2020

I feel honored to have had the privilege of teaching you some cardio and wish you all the best of luck in your future studies.  Please feel free to contact me on any topic including of course questions for pulmonary and renal physiology.