Tony Breu
@tonybreu.bsky.social
Hospitalist, VA Boston Healthcare System. Co-host, Curious Clinicians Podcast
8/
The mechanism described above helps explain why other ineffective osmoles that increase serum osmolarity (e.g., glucose) are not independent drivers of thirst.
t.ly/odecD
The mechanism described above helps explain why other ineffective osmoles that increase serum osmolarity (e.g., glucose) are not independent drivers of thirst.
t.ly/odecD
November 28, 2024 at 2:41 AM
8/
The mechanism described above helps explain why other ineffective osmoles that increase serum osmolarity (e.g., glucose) are not independent drivers of thirst.
t.ly/odecD
The mechanism described above helps explain why other ineffective osmoles that increase serum osmolarity (e.g., glucose) are not independent drivers of thirst.
t.ly/odecD
7/
The explanation above leads to a beautiful symmetry of thirst promoters.
Either...
➤EXTRAcellular volume depletion
...or...
➤INTRAcellular volume depletion...
...will make you seek water.
The explanation above leads to a beautiful symmetry of thirst promoters.
Either...
➤EXTRAcellular volume depletion
...or...
➤INTRAcellular volume depletion...
...will make you seek water.
November 28, 2024 at 2:41 AM
7/
The explanation above leads to a beautiful symmetry of thirst promoters.
Either...
➤EXTRAcellular volume depletion
...or...
➤INTRAcellular volume depletion...
...will make you seek water.
The explanation above leads to a beautiful symmetry of thirst promoters.
Either...
➤EXTRAcellular volume depletion
...or...
➤INTRAcellular volume depletion...
...will make you seek water.
6/
What is the "sensor" for cellular dehydration?
It appears that transient receptor potential vanilloid 1 (TRPV1) is key. TRPV1 is a non-selective cation channel that detects harmful stimuli like heat and capsaicin.
💡 It is also activated by cell shrinking!
t.ly/lqhvy
What is the "sensor" for cellular dehydration?
It appears that transient receptor potential vanilloid 1 (TRPV1) is key. TRPV1 is a non-selective cation channel that detects harmful stimuli like heat and capsaicin.
💡 It is also activated by cell shrinking!
t.ly/lqhvy
November 28, 2024 at 2:41 AM
6/
What is the "sensor" for cellular dehydration?
It appears that transient receptor potential vanilloid 1 (TRPV1) is key. TRPV1 is a non-selective cation channel that detects harmful stimuli like heat and capsaicin.
💡 It is also activated by cell shrinking!
t.ly/lqhvy
What is the "sensor" for cellular dehydration?
It appears that transient receptor potential vanilloid 1 (TRPV1) is key. TRPV1 is a non-selective cation channel that detects harmful stimuli like heat and capsaicin.
💡 It is also activated by cell shrinking!
t.ly/lqhvy
5/
Based on this experiment, Gilman concluded that it is INTRAcellular dehydration that leads to thirst.
This results from a hypertonic extracellular space (e.g., hypernatremia) and the movement of water outside of cells.
t.ly/It2oB
Based on this experiment, Gilman concluded that it is INTRAcellular dehydration that leads to thirst.
This results from a hypertonic extracellular space (e.g., hypernatremia) and the movement of water outside of cells.
t.ly/It2oB
November 28, 2024 at 2:41 AM
5/
Based on this experiment, Gilman concluded that it is INTRAcellular dehydration that leads to thirst.
This results from a hypertonic extracellular space (e.g., hypernatremia) and the movement of water outside of cells.
t.ly/It2oB
Based on this experiment, Gilman concluded that it is INTRAcellular dehydration that leads to thirst.
This results from a hypertonic extracellular space (e.g., hypernatremia) and the movement of water outside of cells.
t.ly/It2oB
4/
Gilman then made another crucial observation:
💡Only NaCl led to a reduction in serum specific gravity. This suggested a shift of water from the intracellular to the extracellular space.
This only occurs with an effective osmole (e.g., sodium) and not an ineffective osmole (e.g., urea).
Gilman then made another crucial observation:
💡Only NaCl led to a reduction in serum specific gravity. This suggested a shift of water from the intracellular to the extracellular space.
This only occurs with an effective osmole (e.g., sodium) and not an ineffective osmole (e.g., urea).
November 28, 2024 at 2:41 AM
4/
Gilman then made another crucial observation:
💡Only NaCl led to a reduction in serum specific gravity. This suggested a shift of water from the intracellular to the extracellular space.
This only occurs with an effective osmole (e.g., sodium) and not an ineffective osmole (e.g., urea).
Gilman then made another crucial observation:
💡Only NaCl led to a reduction in serum specific gravity. This suggested a shift of water from the intracellular to the extracellular space.
This only occurs with an effective osmole (e.g., sodium) and not an ineffective osmole (e.g., urea).
3/
After 30 minutes, the dogs were offered water, and had blood work drawn. Gilman made two key observations:
🔑 The increase in serum osmolarity with hypertonic NaCl and urea were nearly identical
🔑 Dogs drank significantly more water after hypertonic NaCl injection
t.ly/MIdqH
After 30 minutes, the dogs were offered water, and had blood work drawn. Gilman made two key observations:
🔑 The increase in serum osmolarity with hypertonic NaCl and urea were nearly identical
🔑 Dogs drank significantly more water after hypertonic NaCl injection
t.ly/MIdqH
November 28, 2024 at 2:41 AM
3/
After 30 minutes, the dogs were offered water, and had blood work drawn. Gilman made two key observations:
🔑 The increase in serum osmolarity with hypertonic NaCl and urea were nearly identical
🔑 Dogs drank significantly more water after hypertonic NaCl injection
t.ly/MIdqH
After 30 minutes, the dogs were offered water, and had blood work drawn. Gilman made two key observations:
🔑 The increase in serum osmolarity with hypertonic NaCl and urea were nearly identical
🔑 Dogs drank significantly more water after hypertonic NaCl injection
t.ly/MIdqH
2/
We've known for nearly a century that an increase in serum urea is not a significant driver of thirst.
In 1937, Alfred Gilman published an experiment in which dogs received an IV injection of either:
➤20% NaCl
➤40% urea
Both are hypertonic solutions.
t.ly/MIdqH
We've known for nearly a century that an increase in serum urea is not a significant driver of thirst.
In 1937, Alfred Gilman published an experiment in which dogs received an IV injection of either:
➤20% NaCl
➤40% urea
Both are hypertonic solutions.
t.ly/MIdqH
November 28, 2024 at 2:40 AM
2/
We've known for nearly a century that an increase in serum urea is not a significant driver of thirst.
In 1937, Alfred Gilman published an experiment in which dogs received an IV injection of either:
➤20% NaCl
➤40% urea
Both are hypertonic solutions.
t.ly/MIdqH
We've known for nearly a century that an increase in serum urea is not a significant driver of thirst.
In 1937, Alfred Gilman published an experiment in which dogs received an IV injection of either:
➤20% NaCl
➤40% urea
Both are hypertonic solutions.
t.ly/MIdqH
4/4
It will be interesting to see if nemolizumab, an interleukin-31 receptor alpha antagonist, helps mitigate lymphoma-associated pruritus in the rare case when it becomes refractory.
This drug has been tested in atopic dermatitis with pruritus and was effective.
t.ly/-i6US
It will be interesting to see if nemolizumab, an interleukin-31 receptor alpha antagonist, helps mitigate lymphoma-associated pruritus in the rare case when it becomes refractory.
This drug has been tested in atopic dermatitis with pruritus and was effective.
t.ly/-i6US
November 19, 2024 at 4:10 PM
4/4
It will be interesting to see if nemolizumab, an interleukin-31 receptor alpha antagonist, helps mitigate lymphoma-associated pruritus in the rare case when it becomes refractory.
This drug has been tested in atopic dermatitis with pruritus and was effective.
t.ly/-i6US
It will be interesting to see if nemolizumab, an interleukin-31 receptor alpha antagonist, helps mitigate lymphoma-associated pruritus in the rare case when it becomes refractory.
This drug has been tested in atopic dermatitis with pruritus and was effective.
t.ly/-i6US
3/
The mechanism involves a cytokine unfamiliar to me: IL-31.
In one study of HL and angioimmunoblastic T-cell lymphoma, those with pruritis had higher serum levels of IL-31, IL-1β, and IL-1α than those with lymphoma and no pruritis compared with controls.
t.ly/KxLw9
The mechanism involves a cytokine unfamiliar to me: IL-31.
In one study of HL and angioimmunoblastic T-cell lymphoma, those with pruritis had higher serum levels of IL-31, IL-1β, and IL-1α than those with lymphoma and no pruritis compared with controls.
t.ly/KxLw9
November 19, 2024 at 4:10 PM
3/
The mechanism involves a cytokine unfamiliar to me: IL-31.
In one study of HL and angioimmunoblastic T-cell lymphoma, those with pruritis had higher serum levels of IL-31, IL-1β, and IL-1α than those with lymphoma and no pruritis compared with controls.
t.ly/KxLw9
The mechanism involves a cytokine unfamiliar to me: IL-31.
In one study of HL and angioimmunoblastic T-cell lymphoma, those with pruritis had higher serum levels of IL-31, IL-1β, and IL-1α than those with lymphoma and no pruritis compared with controls.
t.ly/KxLw9
2/
The association between HL (and other lymphomas) and pruritus has prompted many to recommend a chest x-ray as part of the initial work-up when a primary skin disorder isn't present.
A 2013 NEJM review suggests this, as does Up-To-Date.
t.ly/wB5Xv
The association between HL (and other lymphomas) and pruritus has prompted many to recommend a chest x-ray as part of the initial work-up when a primary skin disorder isn't present.
A 2013 NEJM review suggests this, as does Up-To-Date.
t.ly/wB5Xv
November 19, 2024 at 4:10 PM
2/
The association between HL (and other lymphomas) and pruritus has prompted many to recommend a chest x-ray as part of the initial work-up when a primary skin disorder isn't present.
A 2013 NEJM review suggests this, as does Up-To-Date.
t.ly/wB5Xv
The association between HL (and other lymphomas) and pruritus has prompted many to recommend a chest x-ray as part of the initial work-up when a primary skin disorder isn't present.
A 2013 NEJM review suggests this, as does Up-To-Date.
t.ly/wB5Xv
1/4
What is the mechanism of pruritus/itching in Hodgkin Lymphoma (HL)?
For today's Morning Report, Chief Resident Carter Baughman shared a case of HL that presented with months of pruritus. I was surprised to learn that up to 30% of patients with HL present with this symptom.
t.ly/RU2Qj
What is the mechanism of pruritus/itching in Hodgkin Lymphoma (HL)?
For today's Morning Report, Chief Resident Carter Baughman shared a case of HL that presented with months of pruritus. I was surprised to learn that up to 30% of patients with HL present with this symptom.
t.ly/RU2Qj
November 19, 2024 at 4:10 PM
1/4
What is the mechanism of pruritus/itching in Hodgkin Lymphoma (HL)?
For today's Morning Report, Chief Resident Carter Baughman shared a case of HL that presented with months of pruritus. I was surprised to learn that up to 30% of patients with HL present with this symptom.
t.ly/RU2Qj
What is the mechanism of pruritus/itching in Hodgkin Lymphoma (HL)?
For today's Morning Report, Chief Resident Carter Baughman shared a case of HL that presented with months of pruritus. I was surprised to learn that up to 30% of patients with HL present with this symptom.
t.ly/RU2Qj
13/
Many heavier elements have been shown to be superior as contrast agents. Whether we'll see them emerge as replacements for iodine isn't yet clear to me.
Stay tuned!
https://buff.ly/3OaBj2f
Many heavier elements have been shown to be superior as contrast agents. Whether we'll see them emerge as replacements for iodine isn't yet clear to me.
Stay tuned!
https://buff.ly/3OaBj2f
November 16, 2024 at 9:28 PM
13/
Many heavier elements have been shown to be superior as contrast agents. Whether we'll see them emerge as replacements for iodine isn't yet clear to me.
Stay tuned!
https://buff.ly/3OaBj2f
Many heavier elements have been shown to be superior as contrast agents. Whether we'll see them emerge as replacements for iodine isn't yet clear to me.
Stay tuned!
https://buff.ly/3OaBj2f
12/
Even gold (79) has been reexamined. It works but is just a bit too pricey to replace iodine.
https://buff.ly/40Sgv7k
Even gold (79) has been reexamined. It works but is just a bit too pricey to replace iodine.
https://buff.ly/40Sgv7k
November 16, 2024 at 9:28 PM
12/
Even gold (79) has been reexamined. It works but is just a bit too pricey to replace iodine.
https://buff.ly/40Sgv7k
Even gold (79) has been reexamined. It works but is just a bit too pricey to replace iodine.
https://buff.ly/40Sgv7k
11/
If heavier elements can provide more "contrast," why don't we utilize others that are high-Z?
It turns out that this exact question is being explored.
Gadolinium (64), holmium (67), ytterbium (70), hafnium (72), tantalum (73), and tungsten (74) have all been compared to iodine.
If heavier elements can provide more "contrast," why don't we utilize others that are high-Z?
It turns out that this exact question is being explored.
Gadolinium (64), holmium (67), ytterbium (70), hafnium (72), tantalum (73), and tungsten (74) have all been compared to iodine.
November 16, 2024 at 9:28 PM
11/
If heavier elements can provide more "contrast," why don't we utilize others that are high-Z?
It turns out that this exact question is being explored.
Gadolinium (64), holmium (67), ytterbium (70), hafnium (72), tantalum (73), and tungsten (74) have all been compared to iodine.
If heavier elements can provide more "contrast," why don't we utilize others that are high-Z?
It turns out that this exact question is being explored.
Gadolinium (64), holmium (67), ytterbium (70), hafnium (72), tantalum (73), and tungsten (74) have all been compared to iodine.
10/
Our current oral contrast agent (barium) is also a heavy element (atomic number 56).
Notice in this figure from radiopaedia that barium is darker than bone. This makes sense, given that the former is high-Z compared to the latter's calcium and phosphorus.
https://buff.ly/4et6eBK
Our current oral contrast agent (barium) is also a heavy element (atomic number 56).
Notice in this figure from radiopaedia that barium is darker than bone. This makes sense, given that the former is high-Z compared to the latter's calcium and phosphorus.
https://buff.ly/4et6eBK
November 16, 2024 at 9:28 PM
10/
Our current oral contrast agent (barium) is also a heavy element (atomic number 56).
Notice in this figure from radiopaedia that barium is darker than bone. This makes sense, given that the former is high-Z compared to the latter's calcium and phosphorus.
https://buff.ly/4et6eBK
Our current oral contrast agent (barium) is also a heavy element (atomic number 56).
Notice in this figure from radiopaedia that barium is darker than bone. This makes sense, given that the former is high-Z compared to the latter's calcium and phosphorus.
https://buff.ly/4et6eBK
8/
This helps explain why bones appear more opaque on x-rays when compared to surrounding soft tissues.
Bone contains significant amounts of calcium and phosphorus, which are heavier elements than those contained within muscle and fat.
This helps explain why bones appear more opaque on x-rays when compared to surrounding soft tissues.
Bone contains significant amounts of calcium and phosphorus, which are heavier elements than those contained within muscle and fat.
November 16, 2024 at 9:28 PM
8/
This helps explain why bones appear more opaque on x-rays when compared to surrounding soft tissues.
Bone contains significant amounts of calcium and phosphorus, which are heavier elements than those contained within muscle and fat.
This helps explain why bones appear more opaque on x-rays when compared to surrounding soft tissues.
Bone contains significant amounts of calcium and phosphorus, which are heavier elements than those contained within muscle and fat.
7/
Fat, muscle, and other soft tissues are primarily comprised of carbon, hydrogen, nitrogen, and oxygen. These smaller elements absorb few X-rays.
When injected into a blood vessel, iodine will absorb more X-rays, appear more opaque, and provide "contrast" with surrounding soft tissues.
Fat, muscle, and other soft tissues are primarily comprised of carbon, hydrogen, nitrogen, and oxygen. These smaller elements absorb few X-rays.
When injected into a blood vessel, iodine will absorb more X-rays, appear more opaque, and provide "contrast" with surrounding soft tissues.
November 16, 2024 at 9:28 PM
7/
Fat, muscle, and other soft tissues are primarily comprised of carbon, hydrogen, nitrogen, and oxygen. These smaller elements absorb few X-rays.
When injected into a blood vessel, iodine will absorb more X-rays, appear more opaque, and provide "contrast" with surrounding soft tissues.
Fat, muscle, and other soft tissues are primarily comprised of carbon, hydrogen, nitrogen, and oxygen. These smaller elements absorb few X-rays.
When injected into a blood vessel, iodine will absorb more X-rays, appear more opaque, and provide "contrast" with surrounding soft tissues.
6/
But how does the atomic weight of iodine relate to its use as an intravenous contrast? It is precisely this property of iodine that makes it a suitable agent for this purpose.
💡 The higher the atomic number of an element, the greater the absorption of X-rays.
https://buff.ly/3Og7vkM
But how does the atomic weight of iodine relate to its use as an intravenous contrast? It is precisely this property of iodine that makes it a suitable agent for this purpose.
💡 The higher the atomic number of an element, the greater the absorption of X-rays.
https://buff.ly/3Og7vkM
November 16, 2024 at 9:28 PM
6/
But how does the atomic weight of iodine relate to its use as an intravenous contrast? It is precisely this property of iodine that makes it a suitable agent for this purpose.
💡 The higher the atomic number of an element, the greater the absorption of X-rays.
https://buff.ly/3Og7vkM
But how does the atomic weight of iodine relate to its use as an intravenous contrast? It is precisely this property of iodine that makes it a suitable agent for this purpose.
💡 The higher the atomic number of an element, the greater the absorption of X-rays.
https://buff.ly/3Og7vkM
5/
IODINE!
The story of how iodine came to be used by vertebrates is fascinating and may be the focus of a future thread. For now, it is enough to note that...
💡 Iodine is the heaviest element required by humans for biological processes.
https://buff.ly/48RcvWE
IODINE!
The story of how iodine came to be used by vertebrates is fascinating and may be the focus of a future thread. For now, it is enough to note that...
💡 Iodine is the heaviest element required by humans for biological processes.
https://buff.ly/48RcvWE
November 16, 2024 at 9:28 PM
5/
IODINE!
The story of how iodine came to be used by vertebrates is fascinating and may be the focus of a future thread. For now, it is enough to note that...
💡 Iodine is the heaviest element required by humans for biological processes.
https://buff.ly/48RcvWE
IODINE!
The story of how iodine came to be used by vertebrates is fascinating and may be the focus of a future thread. For now, it is enough to note that...
💡 Iodine is the heaviest element required by humans for biological processes.
https://buff.ly/48RcvWE
4/
In fact, when examining the top 30 elements in the human body (by mass), you will again notice that most are low-Z (i.e., have a low atomic number).
But there is one element that is both required and relatively heavy...
https://buff.ly/3YOuTLb
In fact, when examining the top 30 elements in the human body (by mass), you will again notice that most are low-Z (i.e., have a low atomic number).
But there is one element that is both required and relatively heavy...
https://buff.ly/3YOuTLb
November 16, 2024 at 9:28 PM
4/
In fact, when examining the top 30 elements in the human body (by mass), you will again notice that most are low-Z (i.e., have a low atomic number).
But there is one element that is both required and relatively heavy...
https://buff.ly/3YOuTLb
In fact, when examining the top 30 elements in the human body (by mass), you will again notice that most are low-Z (i.e., have a low atomic number).
But there is one element that is both required and relatively heavy...
https://buff.ly/3YOuTLb
3/
One thing you'll notice about these six elements is that they are relatively small (i.e., they have low atomic numbers, aka are low-Z elements).
In addition to being the most prevalent elements in the universe, their low atomic number allows them to more readily form stable chemical bonds.
One thing you'll notice about these six elements is that they are relatively small (i.e., they have low atomic numbers, aka are low-Z elements).
In addition to being the most prevalent elements in the universe, their low atomic number allows them to more readily form stable chemical bonds.
November 16, 2024 at 9:28 PM
3/
One thing you'll notice about these six elements is that they are relatively small (i.e., they have low atomic numbers, aka are low-Z elements).
In addition to being the most prevalent elements in the universe, their low atomic number allows them to more readily form stable chemical bonds.
One thing you'll notice about these six elements is that they are relatively small (i.e., they have low atomic numbers, aka are low-Z elements).
In addition to being the most prevalent elements in the universe, their low atomic number allows them to more readily form stable chemical bonds.
2/
To begin, it's essential to understand which elements make up the human body. Amazingly, just six compose >98% of your weight:
➤Oxygen: 61% (varies based on water composition)
➤Carbon: 23%
➤Hydrogen 10%
➤Nitrogen: 2.6%
➤Calcium: 1.0%
➤Phosphorus: 0.6%
https://buff.ly/3YU4dIY
To begin, it's essential to understand which elements make up the human body. Amazingly, just six compose >98% of your weight:
➤Oxygen: 61% (varies based on water composition)
➤Carbon: 23%
➤Hydrogen 10%
➤Nitrogen: 2.6%
➤Calcium: 1.0%
➤Phosphorus: 0.6%
https://buff.ly/3YU4dIY
November 16, 2024 at 9:28 PM
2/
To begin, it's essential to understand which elements make up the human body. Amazingly, just six compose >98% of your weight:
➤Oxygen: 61% (varies based on water composition)
➤Carbon: 23%
➤Hydrogen 10%
➤Nitrogen: 2.6%
➤Calcium: 1.0%
➤Phosphorus: 0.6%
https://buff.ly/3YU4dIY
To begin, it's essential to understand which elements make up the human body. Amazingly, just six compose >98% of your weight:
➤Oxygen: 61% (varies based on water composition)
➤Carbon: 23%
➤Hydrogen 10%
➤Nitrogen: 2.6%
➤Calcium: 1.0%
➤Phosphorus: 0.6%
https://buff.ly/3YU4dIY
1/14
🤔 Why do we use iodine as an intravenous contrast agent?
The answer requires a review of the composition of the human body and a brief tour of one of my favorites, the Periodic Table of Elements.
🤔 Why do we use iodine as an intravenous contrast agent?
The answer requires a review of the composition of the human body and a brief tour of one of my favorites, the Periodic Table of Elements.
November 16, 2024 at 9:28 PM
1/14
🤔 Why do we use iodine as an intravenous contrast agent?
The answer requires a review of the composition of the human body and a brief tour of one of my favorites, the Periodic Table of Elements.
🤔 Why do we use iodine as an intravenous contrast agent?
The answer requires a review of the composition of the human body and a brief tour of one of my favorites, the Periodic Table of Elements.
Recently, I came across a meta-analysis of corticosteroids in acute MI. Most studies are from the 70s and 80s, predating current therapies. That said, the authors reported:
☞ Decreased mortality: OR 0.74, 95% CI 0.59-0.94
☞ RCTs alone: OR 0.95, 95% CI 0.72-1.26…
☞ Decreased mortality: OR 0.74, 95% CI 0.59-0.94
☞ RCTs alone: OR 0.95, 95% CI 0.72-1.26…
November 16, 2024 at 9:02 AM
Recently, I came across a meta-analysis of corticosteroids in acute MI. Most studies are from the 70s and 80s, predating current therapies. That said, the authors reported:
☞ Decreased mortality: OR 0.74, 95% CI 0.59-0.94
☞ RCTs alone: OR 0.95, 95% CI 0.72-1.26…
☞ Decreased mortality: OR 0.74, 95% CI 0.59-0.94
☞ RCTs alone: OR 0.95, 95% CI 0.72-1.26…
Recently, I came across a meta-analysis of corticosteroids in acute MI. Most studies are from the 70s and 80s, predating current therapies. That said, the authors reported:
☞ Decreased mortality: OR 0.74, 95% CI 0.59-0.94
☞ RCTs alone: OR 0.95, 95% CI 0.72-1.26
https://buff.ly/40P2RBV
☞ Decreased mortality: OR 0.74, 95% CI 0.59-0.94
☞ RCTs alone: OR 0.95, 95% CI 0.72-1.26
https://buff.ly/40P2RBV
November 13, 2024 at 10:02 PM
Recently, I came across a meta-analysis of corticosteroids in acute MI. Most studies are from the 70s and 80s, predating current therapies. That said, the authors reported:
☞ Decreased mortality: OR 0.74, 95% CI 0.59-0.94
☞ RCTs alone: OR 0.95, 95% CI 0.72-1.26
https://buff.ly/40P2RBV
☞ Decreased mortality: OR 0.74, 95% CI 0.59-0.94
☞ RCTs alone: OR 0.95, 95% CI 0.72-1.26
https://buff.ly/40P2RBV