Hey everybody, this is Medicosis Perfectionalis, the Rolls-Royce of medical education. It's Medicosis Perfectionalis because medicine literally makes perfect sense. This is my biochemstriple labeless.
Today we'll talk about vitamin A or retinoids. We have three forms of vitamin A. We have retin-L, retin-ol, and retinoic acid, collectively known as retinoids. Vitamin A is very important for your eyes and for your epithelium.
With that said, now let's get started. Please make sure to watch these videos in order. Let's start by answering the question of the previous video. Please name three substances that determine the natural skin tone. And the answer is melanin, beta-carotene, and hemoglobin.
Melanin is the most important one. If you have more melanin, you have dark skin. Less melanin, you have light skin.
This is normal. But pathologically, too much melanin, hyperpigmentation, too little melanin, albinism. How about too much beta carotene? Hypercarotinemia.
Third, hemoglobin. If you have less hemoglobin, you're pale. This is anemia.
If you have a different kind of hemoglobin called metahemoglobin, you will have a chocolate-colored blood and you have brown-slash-gray-slash-cyanotic skin. If you remember my previous questions, we have talked about the story of ancient Egyptians feeding liver organ meat to patients in order to treat. and ophthalmological disease and this was the story of vitamin A deficiency.
Liver has lots of vitamin A and vitamin A deficiency can lead to vision problem especially nyctalopia or night blindness among others. Now let me tell you the story of 10 different patients who have one thing in common. Patient number one present with bilateral dry eyes, dry conjunctivae aka conjunctival xerosis or xerophthalmia. At night, you should see this. But our patient came to us with problems seeing at night.
And this is called night blindness. Patient number three came to us with bilateral parotid swelling. Oh, medicos, I know this.
This is mumps. Well, the vaccines are up to date, so try again. Patient number four presented with fundus xerophthalmicus, aka tiny white spots beneath the retinal vessels sparing the macula. Patient number five presented with some teeny tiny white spots on the sclera. They resemble brie cheese with a foamy appearance on the temporal side of the eye, not the nasal side, most of the time.
Moreover, this patient had conjunctival xerosis or xerophthalmia or dry eye. Patient number six presents with dry skin. Patient number seven presents with keratomalacia.
Also, he had corneal ulcers. Patient number eight is a kid from Northern Europe or any area of Europe, presents with dilated bronchi and CT scan of the chest. Every day he coughs cupfuls of pus. His parents have to change his position many times a day to get all of this gunk outside of his lungs. His putum is so thick.
CT scan of the abdomen shows cysts and fibrosis in the pancreas. Amylase and lipase levels in the blood are low. Mom and dad are carriers for this disease, but they did not show symptoms. This patient suffers from recurrent infections, recurrent diarrhea, and a rare form of esophagitis due to hyperkeratosis.
Our ninth patient presented with a skin condition known as phreoderma and follicular hyperkeratosis. The patient also had iron deficiency anemia. Okay, I'll give the patient some iron. You gave the patient some iron, the patient is not responding to the treatment. Our last patient had bone and teeth problems.
Bone problems included decreased osteoblastic activity, the bone becomes more cancellous, and as you know cancellous bone is more friable and less strong than compact bone. Teeth problem included thinning of the enamel and chalky deposits on the surface. What all of these patients had in common is vitamin A deficiency, and this is the story of today's video.
I've told you, it's the Rolls-Royce of medical education. Today we'll talk about vitamins, vitamin A, the chemistry of vitamin sources, of vitamin metabolism, deficiency of vitamin A, causes of deficiency, clinical picture of the deficiency, how to diagnose and treat the deficiency, and what happened with hypervitaminosis A. For the 25th time, vitamins are organic molecules, micronutrients, they are essential, your body cannot make them, therefore you have to eat them in your diet.
Vitamin A is a fat soluble vitamin, therefore deficiency is less likely, but toxicity is more likely, at least theoretically. If it's a fat soluble vitamin, it's gonna need a good gut, a robust pancreas and a doozy liver if you have malabsorption syndrome you will suffer from vitamin a deficiency here are your water soluble vitamins and fat soluble vitamins and today's topic is vitamin a If you want to summarize vitamin A in two words, word number one, antioxidant. It also helps rhodopsin, which is a protein in your eye, especially the rods of your retina.
And the rods are responsible for night vision, not color vision. That's the job of the cones. Vitamin A structure.
We have retinol, retinal, and retinoic acid. Ol is an alcohol, al is an aldehyde, and retinoic acid is a carboxylic acid. and therefore alcohol will end up in CH2OH, the aldehyde always has CHO, carboxylic acid is COOH, carboxy from CO2, CO2. Collectively we call them meridianoids, and all of them have the beta-ionine rings. All of them are present in the all-trans form with four double bonds, and they have limited stability.
Pro-vitamins are substances that are gonna give us some vitamins. Example, carotenes whether it's alpha carotene beta carotene or gamma carotene you get carotene from the carrots next carotenes will be activated by e di oxygenase and e reductase and they will give you the doozy active vitamin a we call them retinoids such as retinol retinol or retinoic acid where do i get vitamin a from you have natural sources and you have artificial sources artificial the supplements natural liver oil egg yolk butter milk carrots and vegetables So you have green vegetables and yellow vegetables. The required daily allowance is about 3,000 IU per day. The normal blood volume should be about 18 to 60 micrograms per deciliter. Functions of vitamin A include vision, especially night vision.
It helps your rods. Big time. Rods have rhodopsin. It helps with cell division and growth, helps your bone and teeth, epithelialization of your epithelium including your epidermis, metabolism and reproduction.
Vitamin A deficiency in male rats led to infertility, but the female rats were fine. Vitamin A is a fat-soluble vitamin. If it's a fat-soluble vitamin, it needs what? It needs a pancreas. And the pancreas will secrete what?
Lipase, colipase, cholesterol esterase, and phospholipase. They will help you digest and absorb the fat and the fat-soluble vitamins. Also, you need some bile salts from your liver slash gallbladder. You eat some sources of vitamin A and make your mama happy.
These sources have vitamin A ester. And your gut has a cholesterol esterase. Estrace is gonna break this ester down into fatty acids and free vitamin A.
This free retinol is going to be absorbed and re-estratified in the gut epithelium and it will go to the blood. From the blood will go to your liver and vitamin A will be stored for your liver in the form of a retinol ester. Moreover, when you eat carotenes, these are pro-vitamins. Who's going to convert them to active vitamins?
Your liver. Next, your liver can give some vitamin A to your eyes, to your cells, to your bones, your teeth, epithelium, etc. So the liver will dump it in the blood. But as you know, vitamin A is fat-soluble vitamin. And your blood is made of what?
Plasma. Water. Fat cannot float in water because fat and water do not mix. And therefore, vitamin A has to jump on top of a plasma protein.
We have two of these. We have the R-BP and the R-ABP, retinol-binding protein and retinoic acid-binding protein. Vitamin A prevents metaplasia, but if you have vitamin A deficiency, this can initiate a signal which can lead to metaplasia.
Of course, metaplasia is not fun. It can progress to dysplasia and, God forbid, cancer. If you remember your biochemistry, this was alcohol.
When alcohol enters into your body by alcohol dehydrogenase, it's gonna be converted into aldehyde. By an aldehyde dehydrogenase, the aldehyde is gonna become an acid. Suppose that the alcohol was methanol.
By a methanol dehydrogenase, it will become formaldehyde. By an aldehyde dehydrogenase, the formaldehyde will become formic acid, toxic to your eyes. If the alcohol, however, with ethanol, by an ethanol dehydrogenase, it will become acetaldehyde.
By an acetaldehyde dehydrogenase, it will become acetic acid, toxic to your kidney. Hashtag kidney stones or nephrolithiasis. Now let's add some pharmacology, baby. What if we can inhibit the alcohol dehydrogenase?
Oh, you can give me a drug known as Fumepizole. Can I inhibit the acetaldehyde dehydrogenase? Yes.
Give me the famous drug disulfiram, aka Antabuse. When you give me this drug, acetaldehyde will accumulate. of course, an acetaldehyde will make me hate myself so that I may stop drinking alcohol, because I'm such a raging alcoholic.
Just joking. By the same token, if the alcohol was retinol, which comes from carotene, retinol by a retinol dehydrogenase requires zinc as a cofactor, it will become an aldehyde called retin-L. L because it's an aldehyde.
By an aldehyde, dehydrogenase also needs zinc as a cofactor, will give you retinoic acid. acid. And this is a great example of a Mineral deficiency that can lead to a vitamin deficiency. If you remember, zinc deficiency leads to a condition known as acrodermatitis enteropathica.
Say it one more time because it was so beautiful. Acro, extremities, dermatitis, skin inflammation. Oh, skin inflammation. I've just told you that vitamin A... is important for epithelization.
It's important for your normal robust epithelium, including your epidermis. Oh, without zinc, there is no active form of vitamin A. There is no normal epithelium.
You're gonna suffer from keratinization and acrodermatitis enteropathica. Medicine makes so much sense once you understand what the flip you're talking about. Okay, one more time.
Is vitamin A fat-soluble or not soluble? It's fat-soluble. Fat-soluble can enter through the lipid by layer. Oh yeah, fat can dissolve in fat. Since the cell membrane is made of fat, this fat can enter into the cell smoothly by diffusion.
So the receptor will not be outside. It will be inside because you can enter. So we'll put the receptor on the freaking nucleus. And this receptor is a zinc finger. What the flip is a zinc finger?
A zinc finger is linked to some enhancer elements known as RxRe. R and R stands for retinoids and retinol receptor. Therefore, RXREs are enhancer elements. They do what?
They modulate gene expression. Examples include RAR-alpha and REX. If you remember my hematology playlist, we have talked about RAR-alpha in a disease known as acute promyelocytic leukemia, aka acute myeloid leukemia subtype M3. How did we treat this stinking disease? Vitamin A. Benefits of vitamin A.
We have clinical benefits and biochemical benefits. Clinical benefits. You can give vitamin A to treat vitamin A deficiency. No kidding. To treat acne.
To treat acute promyelocytic leukemia. To treat measles. Maybe to treat hairy, leucoplakia, and retinitis pigmentosa.
Biochemical functions include vision, especially night vision, cell division, bone and teeth, epithelialization, metabolism, and reproduction. Vitamin A and treatment of acne. If it's mild acne, give topical vitamin A.
If it's severe cystic acne, give oral vitamin A. Please be careful. Vitamin A is a teratogenic. It can also end the pregnancy.
Never, ever, ever, ever, ever prescribe vitamin A. to a female in her childbearing age without getting a pregnancy test first. Get the pregnancy test.
If the pregnancy test is negative, you can go ahead and give vitamin A. If you forget to do this, this is a mistake that can help you end behind bars, which in turn can help you develop a painless chancre, if you know what I'm saying. There is another famous medication that you should never prescribe without a pregnancy test first, and the answer is methotrexate.
Let's talk about vitamin A and the treatment of acute pro-myoesthetic leukemia, which is a subtype of acute myeloid leukemia. As you know, we divide leukemia into acute and chronic, and then acute is ALL or AML, chronic is CML or CLL. If you want to learn more, watch my hematology and oncology playlist. The old classification of AML is here.
If you see, M3 is known as acute pro-myelostatic leukemia. It has a translocation between chromosomes 15 and 17. It has a very good prognosis. Why?
Because you can treat it with a vitamin A. and here is an example of vitamin that can treat cancer. Tell me more about this acute probe myelocytic leukemia. It has the 15-17 translocation between PML and RAR alpha. It's associated with DIC, so we have three letters and we have M3.
It has very good prognosis and you treat it with four letters. All-trans-rethinoic acid, which is a vitamin A. If vitamin A fails, try arsenic trioxide.
and here is an example of a freaking toxin a poison that can treat cancer it can kill your cancer it can also kill your own freaking cells there are no solutions in life there are only trade-offs vitamin a i have good news and bad news good news it can treat your apml by inducing maturation of these primitive pro myelocytes that's why we call it pro myelocytic these pro myelocytes will grow up differentiate and become neutrophils these neutrophils will die hashtag e-baptosis Bad news! Vitamin A can lead to differentiation syndrome. Here is chromosome 15. It has the PML on it, which is pro-myocytic leukemia gene.
And here is chromosome 17. It has the original cast receptor alpha, or RAR-alpha, on it. This translocation between 15 and 17 will lead to fusion of these two. We call it PML-RAR-alpha fusion gene, which will give you a fusion protein, which will lead to arrest of differentiation. That's why you have immature, stupid, pro-myelocytic cells. and that's why vitamin A can treat you because it will help these immature cells develop, differentiate, and grow up.
But when they differentiate this can lead to differentiation syndrome and this is a side effect of ATRA. So here is the patient with APML. You gave the patient vitamin A. Differentiation led to differentiation syndrome with fever, pleural effusion, respiratory distress and hypoxia, volume overload, pericardial effusion, hypotension and renal problems. How do I treat it?
Stop the ATRA, give high dose dexamethasone. Why do we call this differentiation syndrome? Because ATRA help those immature pro-myelistic cells develop into neutrophils and then die. Development is equivalent to differentiation. And there are two theories to this disease and they are discussed in my video titled differentiation syndrome in my hematology oncology playlist.
Now you know about vitamin A, let's talk about vitamin A deficiency. Vitamin deficiency, what the flake does that mean? You have decreased vitamin level in your blood, and we have two types.
Primary deficiency, you're not eating it. Or secondary deficiency, you're eating it, but you're not absorbing it, such as malabsorption syndrome. What are the causes of vitamin A deficiency? A problem in your diet, problem with the absorption, or a problem in your liver. So dietary deficiency, fat malabsorption, blame your liver, blame your pancreas, or blame your gut.
Blame your liver and biliary system. Example, biliary atresia, primary biliary cholangitis, primary sclerosing cholangitis, familial intrahepatic cholestasis. Blame the pancreas, cystic fibrosis, and chronic pancreatitis.
Blame your gut, celiac disease, inflammatory bowel disease, and short bowel syndrome, terminal iliopter rejection, maybe to treat Crohn's. And this is something that will give you vitamin B12 deficiency, and vitamin A deficiency, and vitamin K deficiency, and vitamin D deficiency, and vitamin E deficiency. Vitamin A, physiology, and pathology. Functions of vitamin A include the retinal rods.
We call it rhodopsin. IN means protein most of the time. What does rod mean?
Rod is your rod in your retina. What does ops mean? For optic vision.
Therefore, deficiency of vitamin A will lead to, oh, problems in my rods. And the rods are responsible for night vision. Now I have nice blindness or nyctalopia. Nyct means night.
Opia means vision. A means no. Vitamin A is important in normal cell differentiation and preventing squamous cell metaplasia. If you have vitamin A deficiency, you can get squamous cell metaplasia and abnormal epithelium. Vitamin A is important for your epithelium and to prevent keratinization, which is excessive keratin formation.
Therefore, vitamin A deficiency will lead to keratinization, keratomalacia, and when you have bad epithelium, like the epithelium in your respiratory system or your GI system, you can get infections. Vitamin A is good for bones and teeth. Without it, you can get bone and teeth problems. Vitamin A is good for your mucus-secreting epithelium and for your immune system.
Without it, you get zero cystic, dry skin, zero phthalmia, dry eyes, diarrhea, because the mucus membrane of your gut is screwed. Without your immune system, you can get infections. Symptoms of vitamin A deficiency include bilateral dry eyes or dry conjunctiva or conjunctival cirrhosis or xerophthalmia, night blindness or nectalopia, bilateral parotid swelling, as well as fundus xerophthalmicus. These are tiny, tiny white spots beneath the vessels sparing the macula. These white spots that you see on the temporal part of the sclera are known as B2 spots.
They look foamy, they look like breeches. And you have conjunctival xerosis xerothelmica and keratomalacia, dry skin. Cystic fibrosis will lead to, oh, malabsorption of what? Of fat and fat-soluble vitamins because your pancreas is screwed. We call it cystic fibrosis because we have cysts in the pancreas and fibrosis in the pancreas, not the lungs.
Vitamin A deficiency can lead to iron deficiency anemia that is refractory to iron supplements. It can also lead to phryoderma with follicular hyperkeratosis. Keratinization, baby. Vitamin A deficiency can lead to bone problems and teeth problems, especially thinning of the enamel. Okay, medicosis, now vitamin A deficiency is horrible.
Now I'm gonna get tons of vitamin A. Well, there are no solutions in life. There are only incremental trade-offs. Vitamin A deficiency is not fun. Hypervitaminosis A is also not fun.
Acutely you can develop blurry vision, headache, dizziness, nausea, and vomiting. Symptoms that are confusing with brain tumors. Chronically, lots of vitamin A can lead to weight loss, anorexia, nausea, and vomiting, and even bone fractures.
There was a story about a carpenter who was stranded in Antarctica. This doofus ate the liver of the polar bear, which has tons of vitamin A. He developed symptoms of hypervitaminosis A.
some pearls for the pros trans-thyretin oh i love this name i n means what protein how about thyroid oh from thyroid how about trans transporter it's a carrier protein for transport rotation of thyroid hormone that's why we call trans-thyroidine and vitamin a as you know vitamin a is fat soluble it cannot float in the serum alone it has to be bound to a plasma protein trans-thyroidine is a precursor protein for amyloid if you remember your pathology Another pearl, vitamin E can help you absorb vitamin A. And here is an example of a vitamin that can help you absorb another vitamin. Conversely, here's an example of a vitamin deficiency that can lead to another vitamin deficiency. Don't ever, ever, ever give warfarin and vitamin E together because both of them inhibit vitamin K-dependent gamma carboxylation. Both of them will inhibit coagulation.
Hashtag bleeding. If I ever hear that you gave the patient warfarin and vitamin E, I will kick your... gluteus minimus metaphorically speaking question of the day we know that jaundice can lead to yellow skin hyperkerogenemia can lead to also yellow skin how can you tell the difference between jaundice and hyperkerogenemia clinically without resorting to the lab any doofus can order some lab tests but it takes a robust clinician to differentiate between the two so let me know the answer in the comment section you will find the answer in the next videos If you like this video, you will absolutely adore my antibiotics course. Go to medicosisperfectionist.com, download these videos, these notes, and these cases with their answers. There is no subscription.
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