Transcription
Hey everybody, thank you for watching. This is Medicals Perfection Analyst. Let's talk about vitamin B12 deficiency. This is a series on hematology. I've been talking about anemia for a long time. Previous videos include macrocytic anemia introduction and folate deficiency. It will make much more sense if you go ahead and watch those previous videos first. But anyway, welcome. Vitamin B12 deficiency.
Okay, so here, anemia, certain pale headache, angina, murmur—symptoms of anemia. Neurological symptoms, and of course, vitamin B12 is a macrocytic anemia. However, folate deficiency had symptoms of anemia but no neurological symptoms—huge difference. So, as you know, the mean corpuscular volume can determine if the anemia is microcytic, normal, or macrocytic. Macrocytic anemia will have more than 100 femtoliters of the MCV. Macrocytic anemia has two different types: megaloblastic and non-megaloblastic. Vitamin B12 and folate are from the megaloblastic causes. Why megaloblastic? Because also we have hyper-segmented neutrophils. Alright, so, and also we can have pancytopenia and other issues such as ineffective hematopoiesis.
Now, to the big story of vitamin B12 absorption. Please pay close attention. So, we eat vitamin B12 from the diet, preferably animal protein. That does not mean that there are no other sources of vitamin B12, but animal sources are the best, and these will include meat, eggs, dairy products. So this is your vitamin. So here are your vitamins. It will be bound to animal protein. Thanks to the salivary enzyme amylase, we'll break down this relationship between the vitamin B12 and the animal protein. So break them. And now the cobalamin is kind of free. Also, your salivary glands are amazing; they secrete something called the R protein. The R protein will protect the vitamin B12 from the gastric acid when it goes to the stomach. So now we are in the stomach; we have this vitamin B12 and this animal protein. The hydrochloric acid will convert pepsinogen into pepsin. Also, pepsin will do the same thing; it will destroy the relationship or the bond between the cobalamin and the protein. So now cobalamin is free, but the stomach acid can destroy the cobalamin; that's why the R protein is here. Thank you, salivary glands. Now vitamin B12 can be bound to the R protein. Also, the gastric acid secretes R protein, so R protein can be salivary, can be gastric, and as we will know, can be biliary. Anyways, it's an R protein; it serves the same function to bind to vitamin B12 and protects it from the gastric acid. Also, your amazing stomach will secrete something called the intrinsic factor. This intrinsic factor is very important for the absorption of vitamin B12.
Now let's go out of the stomach. Here, when we reach the small intestine, the pancreas will secrete its pancreatic secretion, and also the bile will secrete the R protein. They will go together in the duodenum. Here we have the cobalamin and the R protein bound together—why? To protect them from the gastric acid. But now we don't need the R protein anymore, so the pancreatic enzyme, not amylase but protease, will destroy this relationship between them. Okay, so they will get divorced, and now the cobalamin is free, but not free; it will bind the intrinsic factor from the stomach. So the intrinsic factor is made where? In the stomach, but it starts binding to vitamin B12 in the small intestine. Okay, same thing with the R protein from the salivary glands—made in the saliva but doesn't bind with vitamin B12 until we are in the stomach. Let's go from the small intestine to the famous terminal ileum, where the actual absorption of vitamin B12 will occur. But now the terminal ileum cells will destroy the relationship between the vitamin B12 and the intrinsic factor, and then the vitamin B12 will bind to our amazing transcobalamin. Cobalamin is vitamin B12; trans means transportation. So transcobalamin is responsible for the transportation of vitamin B12 in the bloodstream. Once vitamin B12 is in the bloodstream, it has two choices: to go to cells to be utilized or to go to the liver to be stored for years. If you have watched my previous video on folate deficiency, folic acid is only stored in the liver for around, like, four months. I'm telling you, years—maybe nine years. So folic acid, months; vitamin B12, years. It's more difficult to get vitamin B12 deficiency than it is to get folate deficiency. I hope this is clear.
So to summarize the steps: You eat vitamin B12 bound to animal products. Yeah, the salivary glands produce amylase as well as the R protein. Also, the stomach produces what? It will sever the relationship between vitamin B12 and the animal protein; it will produce R protein; it will produce the intrinsic factor. Thank you, stomach. Pancreas produces its secretion, protease enzyme; it will divorce the vitamin B12 from the R protein and make it bound and make it bind to the intrinsic factor. The ileum will absorb the transcobalamin and make it bind the transcobalamin that can go to the bloodstream. So any problem in any of these processes will cause vitamin B12 deficiency. Let's go to the first step: eating diet. Dietary deficiency, which is rare, except if you are a strict vegan. Okay, these people only eat vegetables. These diets have very few vitamin B12, and it's more hard to absorb it. Salivary glands—maybe salivary gland disease, but that's rare. Stomach—how about achlorhydria or pernicious anemia? It will lead to a vitamin B12 deficiency. Pancreatic insufficiency will lead to vitamin B12 deficiency. Terminal ileum resection or damage of the terminal ileum by Crohn's disease or by the fish tapeworm, okay, also known as Diphyllobothrium latum. Wow.
Let's summarize: Imagine an alcoholic, strict vegan with pernicious anemia. He has just left the hospital where he had terminal ileal resection because of Crohn's disease. He's now going to eat some sushi to get fish tapeworm because he cannot have terminal ileum disease if he doesn't have a terminal ileum. Of course, we respect all vegans; this is not to offend anybody. Of course, eating vegetables is better than eating seven steaks a day after coming from a hot dog contest. So that's the story. Morning Glory. If you remember the previous video on folate deficiency, we have talked about homocysteinemia. So in order for folate to participate in DNA synthesis, it had to get rid of the methyl group on the vitamin B12, which gets rid of the methyl group on the homocysteine. Homocysteine blood plus methyl equals methionine. So symptoms will include homocysteinemia. Please go ahead and watch the previous video if you'd like to know more about folate. Keep in mind that folate is a more common cause than vitamin B12 to cause homocysteinemia.
Now to another story: We have something called propionyl CoA. Participate in this propionyl CoA, which has three carbons, is odd-chain fatty acid oxidation as well as three amino acids: methionine, isoleucine, and valine. Thank you, carboxylase, by help of biotin or vitamin B7. Now we have methylmalonyl coenzyme A, which will convert the methylmalonic CoA into succinylcholine. Succinylcholine goes to the Krebs cycle where gluconeogenesis will occur. Gluconeogenesis is forming glucose from new sources—suggest fatty acid. So these fatty acids or fat now will be glucose—that's amazing. In vitamin B12 deficiency, methylmalonyl CoA cannot work, so succinyl CoA will be decreased; energy production will be decreased; methylmalonyl coenzyme A. So this is a huge difference between folate deficiency and B12 deficiency. Only B12 deficiency will have a high methylmalonyl coenzyme A. B12 deficiency, methylmalonic acid will increase; propionyl CoA will increase; they will replace the acetyl CoA in the membrane of the neuron. Okay, so now the myelin sheath cannot be formed, leading to demyelination in the spinal cord, the peripheral nerves, as well as the brain.
Okay, what are the clinical signs and symptoms? So we have some clinical signs and symptoms related to the etiology, related to anemia, or related to vitamin B12. Related to the etiology, I've mentioned them before: vague and related to pernicious anemia, chronic pancreatitis, Crohn's disease, fish tapeworm, ileal resection, etc. Related to anemia: Same symptoms—start pale, pale and tired; sometimes I can have angina; sometimes I have murmur; also headache, exercise intolerance, etc. Related to the vitamin B12 itself: glossitis. And if you have watched it on my video on the overall changes in different diseases, I've mentioned a lot of other diseases as well: lemon-yellow skin and neurological symptoms. What's the most common neurological sequelae? It's peripheral neuropathy. What's the most dangerous? Subacute combined degeneration of the spinal cord. Also, you can get dementia. Keep in mind you can have neurological symptoms in vitamin B12 deficiency without symptoms of anemia, so please keep that in mind. So here is the subacute combined degeneration of the cord. Demyelination will occur at three sites: one, the dorsal column. So what will happen? Loss of vibration and proprioception sensation. Fine. Second, lateral corticospinal tract will be affected, leading to weakness. Okay, there are two different types: spasticity or rigidity. Here we will have spasticity. Third, the dorsal spinocerebellar tract. What will happen? Ataxia. So we'll have a patient who cannot sense vibration or his joints; he is kind of wobbly and cannot walk well, and also you will have weakness.
Lab results in B12 deficiency: What about hemoglobin? Will be decreased. How about hematocrit? Decreased. MCV? Increased. White blood cells and platelets may be decreased—why? Pancytopenia. Serum B12? Decreased. Serum homocysteine? Increased. Serum—I'm sorry, I'm sorry, sorry—serum homocysteine is increased in both folate deficiency and B12 deficiency. However, serum methylmalonic acid is increased only in B12 deficiency. This does not happen in folate deficiency. The way to remember it: We have homocysteine and methylmalonic acid; both of them are elevated in B12 deficiency. Folate will only have the homocysteine. So both elevated in B12 deficiency. However, the peripheral smear will have macro-ovalocytes; large RBCs will have hyper-segmented neutrophils with more than five lobes; pancytopenia. Bone marrow biopsy will yield megaloblastic nucleated cells. Schilling tests can diagnose B12 deficiency; it's rarely done. Maybe I'll discuss it in a separate video. What's the treatment of B12 deficiency? Give B12 intramuscularly. And also remember, pharmacological doses of folate may improve both folic acid deficiency as well as vitamin B12 deficiency. However, giving folic acid to a B12-deficient patient will never improve the neurological symptoms. Thank you very much, and let me see you in the next video. Please consider subscribing and like the video, and I can't thank you enough.