Nick Mark MD Profile picture
Apr 23, 2022 30 tweets 15 min read Read on X
Part 6️⃣ in my extremes of animal physiology #tweetorial series:

Case 1: How low can PaO2 go?

You are called by the lab about an abnormal ABG result.
pH 7.5 / PaCO2 20 / PaO2 22 / HCO3 15

“That’s gotta be venous” they say.
“No” you reply, “Its from a ___"
1/
Answer: bar-headed goose!

The Himalayan summits are almost lifeless.

In the midst of this barren landscape, breathless climbers have heard the thrum of wings & the honking of geese above their heads.

How can these geese breathe so easily while flying at over 8000m?
2/
Bar headed geese have many amazing adaptions to altitude: large hearts, specialized hemoglobins, highly capillarized muscles with dense mitochondria, and cerebral insensitivity to hypocapnia.

But most of all they have amazing lung physiology!

ncbi.nlm.nih.gov/pmc/articles/P…
3/
Unlike mammalian lungs with reciprocating airflow in & out, birds have continuous airflow from cranial to caudal air sacs.
This reduces dead space & enables a denser network of airways & blood vessels, with a highly efficient countercurrent exchange.
erj.ersjournals.com/content/29/1/11
4/
Clinical aside: countercurrent flow across thin tubules also explains why an ECMO membrane lung is so efficient.

Look at this oxygenator I cut open: Just like the bird lung, gas flow is opposite to the direction of blood flow.

Countercurrents rock!
5/
How about climbers?
Their ABG has a greater respiratory alkalosis than a goose
We know because 4 climbers drew femoral ABGs at 8400m (at rest w/o supplemental O2)

PaO2 of 24 & SpO2 of 54%1 These are truly the limits of human physiology!
pubmed.ncbi.nlm.nih.gov/19129527/
6/
This bring up an important question: how do we measure ABGs in flying birds?
Answer: we don’t!

To measure ABGs, they *simulated* high altitude flight by running geese on treadmills under hypoxic conditions!
Yes that Goose has a Swan!
pubmed.ncbi.nlm.nih.gov/2506620/
7/
How good are bird lungs? Or put another way, how high can birds fly?
We don’t know!

We know that Rüppell's Griffon Vulture can fly to *at least* 37,000 feet because one got struck by an airliner at that altitude.

37,000 feet (11,300m) has an O2 tension of just 36 mmHg!
8/
Case 2: extreme bronchoscopy

Some docs feel like it's too hard to perform a bronchoscopy outside the controlled environment of the bronch suite.

In which of the following situations has bronchoscopy been successfully performed?
9/
Answer: all of the above!

🐘 Elephants *frequently* contract TB. Bronchoscopy has been performed in elephants (it doesn’t look easy) & apparently a trunk nerve block helps!

bit.ly/3EH7zoi
10/
Clinical 🥡:
TB is common in elephants (2% of Africa Elephants & 12% of Asian Elephants have TB).
People who work around elephants can get TB from them. Remember this the next time you evaluate a zookeeper with fevers & night sweats!

11/
🐬 bronchoscopy is possible but has some challenges.

First the laryngeal spout - an amazing water/pressure tight organ - must be anesthetized & passed, but it only opens for a fraction of a second.
This makes navigating human vocal cords seem easy!
12/
Once past the laryngeal spout and within in the trachea, don’t be fooled by a tracheal bronchus!

Many animals including 🐘, 🐐, 🐫, 🐋,🐖, and 1% of humans have a tracheal bronchus.

See my prior 🧵 for more on pig bronchi:

13/
Clinical 🥡:
Tracheal bronchi can cause unexplained lobar collapse in intubated people if the ETT occludes the opening. This can cause unexplained hypoxemia + RUL collapse.
Always consider a pig bronchus on your differential for upper lobe collapse in the ICU!
14/
Finally, there are some unique challenges to interventional pulmonary procedures in dolphins.
For example, you can’t use electrocautery in an animal that has to stay wet!

I highly recommend this article for:
atsjournals.org/doi/full/10.15…
15/
Side-note: great figure legend & denouement!
16/
Galloping horses do sometimes develop stridor.
Even a small tracheal stenosis can cause big problems when your minute ventilation at peak exercise is >1600 L/min!

How can you evaluate exercise induced wheezing in a thoroughbred horse?
17/
Bronchoscopy, of course: turns out it is possible to perform bronchoscopies in galloping horses (on a treadmill) to evaluate for dynamic airway collapse! Crazy!
pubmed.ncbi.nlm.nih.gov/19562896/


18/
Case 3: extreme uremia
You are called about “a very abnormal chemistry panel”
“This has gotta be incompatible with life!” the caller exclaims “They need dialysis ASAP!"
“Not so” you reply, “that’s normal for a ___”
19/
Sodium 282 mmol/L
Potassium 7.3
Chloride 290
Bicarb 3
BUN 1004 mg/dL
Creatinine < 0.1

Osmolarity 1094 mOsm/Kg

This is a normal BMP for a ___
20/
Answer: 🦈 Shark

Sharks are osmoconformers, meaning they adjust their internal osm to match the environment, mostly by retaining urea.
The average osmolality of the ocean is 1000 mOsm/L so that’s what shark’s blood is too!
21/
Interestingly, some 🦈 like the Bull shark are diadromous meaning they can transition between fresh water and salt water.

This requires them to radically alter their blood chemistry - particularly BUN - gradually over a week.

Why gradually?
22/
As the 🦈 transitions from salt to fresh water, its kidneys excrete urea.
Urea shifts out of the cells into the blood, *gradually* decreasing the intracellular Osms.
If the 🦈 dropped its BUN too fast its cells would swell, which would look something like this:
23/
Clinical 🥡:
People with renal failure can have very high BUN too (like over 200!)
Removing BUN too quickly with dialysis can cause cells to swell.

What’s the solution?
Add urea to the dialysate to limit how fast urea can drop!
academic.oup.com/ndt/article/16…
24/
Wrong answers:
In contrast to sharks, which are osmoconformers, Camels, dolphins, and chinchilla are osmoregulators.
They try to maintain a blood chemistry that's dissimilar from their environment. And how they do it is pretty cool!
25/
Camels crank up their renin-angiotensin-aldosterone system (RAAS) to retain salt/fluid when dehydrated.

Camels can tolerate >20 days without water & their Na rises to 175!
But if they take losartan (blocking RAAS) they become even more hypernatremic!
ncbi.nlm.nih.gov/pmc/articles/P…
26/
Clinical 🥡:
For people, like camels, taking ACE inhibitors is a major risk factor for dehydration under hot conditions.
Remember that people on ACEi are at risk for AKI & dehydration. Be suspicious for dehydration in elderly people taking ACEIs!
journals.plos.org/plosone/articl…
27/
🐪🐫 Side-bar: My son wanted to shared a great mnemonic for remembering the types of camels.
Bactrian - B shaped - two humps
Dromendary - D shaped - one hump

(we even made an infographic about it!)
28/
Check out my prior thread for more how desert animals can retain water - including how amazing the Chinchilla is: it can concentrate it's urine to > 7500 mOsm/L (thats a SG > 10.60!)

29/
I hope you’ve enjoyed part 6 in my series on what the extremes of animal physiology can teach us about critical care medicine.

30/30

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More from @nickmmark

May 3
A slightly tricky blood gas case:

77 yo with respiratory distress, RR 30, SpO2 80% on non-rebreather at 15 lpm

CXR & TTE are unrevealing

pH 7.58 / PaCO2 24 / PaO2 >500 / HCO3 22

MetHb 0% CarboxyHb 0%

The ABG looks like this: Image
The answer is sulfhemoglobinemia.

Sulfhemoglobinemia is a *permanently* modified hemoglobin associated with exposure to TMP/SMX, dapsone, phenazopyridine, & other amino & nitro compounds.

It has an altered oxy-hemoglobin dissociation curve.

2/

Image
Image
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Sulfhemoglobinemia is easily confused with methemoglobinemia. Both have very dark colored blood & present with cyanosis. Diagnosis typically requires a specialized lab.

Spoiler: you may have heard that SulfHb is green. It isn’t really. You’re thinking of Vulcans’ blood.

3/
Image
Image
Read 7 tweets
Apr 28
This story is absolutely shocking.

Philip Morris International (PMI) spent millions to influence medical education by buying a series of “CMEs” at Medscape!

How else has big tobacco tried to normalize vaping & influence the medical community?

🧵
1/
theexamination.org/articles/medsc…
Recently it was revealed that Philip Morris International (PMI) had SPONSORED CME materials about smokeless tobacco products on Medscape.

I had the opportunity to review these “CME” materials & they are pretty shocking!
2/

Image
Image
Image
One truly incredible thing about this “CME” was that it has NO DISCLOSURE SLIDE!

The fact that people teaching about vaping don’t disclose their financial ties to the tobacco industry is absolutely bonkers!

Why isn’t there a sunshine act for this?
3/
Read 19 tweets
Jan 27
Damn. Under Trump the White House Medical Unit was a pill-mill. Thousands of ambien & provigil per month.

Worse, for a clinic that doesn’t typically do procedures w/ moderate sedation they sure are they ordering prodigious quantities of morphine, fentanyl, versed, & ketamine…? Image
Honestly, this reminds me of Norman Ohler’s Blitzed.
The AG report was largely concerned with the enormous cost of prescribing these non-genetic meds.

It’s worth pointing out that dispensing prescription meds without documentation is malpractice. In the case of controlled substances it’s also likely a crime.
Read 8 tweets
Oct 28, 2023
It’s October - hockey season - so let’s talk about a hockey/pulmonary case:

A previously healthy 17yo presents with dyspnea, frothy sputum, & orthopnea that began after playing hockey.

In the ED he is tachycardic, tachypneic, mildly hypoxic. He has crackles bilaterally.

Dx?
1/ Image
Before we get to the diagnosis, Inhalation of which of the following could explain his symptoms?

2/
The answer is ZAMBONI DISEASE!

Poorly maintained combustion engines produce carbon monoxide (CO), nitrogen oxides (NO₂), & other volatile organic compounds.

These compounds are heavier than air.

To avoiding melting the ice, there is often minimal ventilation in ice rinks.
3/
Read 10 tweets
Jun 19, 2023
Lots of inane comments from Elon/Rohan bros that vaccines don’t prevent disease.

Let’s debunk these claims:
1. Polio - vaccine introduced 1957
ourworldindata.org/grapher/report…

2. Measles - vaccine introduced 1963
ourworldindata.org/grapher/measle… ImageImage
3. Tetanus - vaccine 1938
cdc.gov/vaccines/pubs/…

4. Diphtheria
researchgate.net/publication/32… ImageImage
5. Hepatitis A - 1996
cdc.gov/mmwr/volumes/6…

6. Hepatitis B - 1982
cdc.gov/mmwr/volumes/6… ImageImage
Read 6 tweets
Jun 8, 2023
The long awaited #COVIDOUT RCT is now in @TheLancet:
- high risk adults randomized to either metformin (MET), ivermectin (IVM), fluvoxamine (FLV) or placebo.
- MET reduced the risk of long COVID (6.3% vs 10.4%; NNT = 24)
- no benefit with IVM or FLV

thelancet.com/journals/lanin…
1/ ImageImageImageImage
COVID-OUT was a large blinded multicenter RCT looking at repurposed oral meds.

The primary outcome was severe COVID; this was one of the *MANY* negative RCTs of ivermectin. (See 🧵👇)

The current study is a planned secondary analysis, looking at the incidence of long COVID.
2/
COVID-OUT was a factorial design enabling efficient evaluation of multiple oral medications in various combinations.

After diagnosis, subjects received meds by next day mail. They were followed up to 300 days (10 months).

Diagnosis of long COVID was made by a synonym survey
3/ ImageImageImage
Read 9 tweets

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