Transcription
Hey guys, what's up? Let's continue our talk on macrocytic anemia. In the previous video, we have talked about an introduction to macrocytic anemia, so please go ahead and watch that video first. So welcome back. Folate deficiency is today's subject.
Again, symptoms of anemia are the same: tired and pale, pale and tired. Sometimes I have angina, sometimes I have a murmur, also headache and exercise intolerance. Depending on the MCV, we have microcytic, normocytic, or macrocytic anemia. In macrocytic anemia, the mean corpuscular volume is more than 100. As you know, there are two types of macrocytic anemia: megaloblastic and non-megaloblastic. What's the main difference? Megaloblastic usually have hypersegmented neutrophils. Of course, you know, think about a megaloblastic process in a patient with macrocytic anemia and also maybe pancytopenia and indirect hyperbilirubinemia. Because, as we have discussed, there are intramedullary hemolysis, cuz these macrocytes or macro-ovalocytes are abnormal; they get phagocytosed by our friend macrophage.
Now let's talk folate. Pay attention, please. Folate is present in green leafy vegetables. We eat folate in the form of polyglutamate. Polyglutamate goes through your esophagus, here, nice stomach, and then in the small intestine. The question of last time was which part of the small intestine is folate absorbed at? The answer is jejunum. Thanks to the enzyme conjugase, it will convert this polyglutamate into monoglutamate. However, pay attention: this conjugase is inhibited by the drug called phenytoin, the anti-seizure medicine. So this monoglutamate, i.e., folate, will go into the blood. This is absorption, and it goes into the bloodstream in the form of methyltetrahydrofolate. But wait, this process of absorption is inhibited by alcohol or oral contraceptive pills. Okay, for this tetrahydrofolate to participate in DNA synthesis, it has to get rid of this methyl group, so it shifts the methyl group and gives it to the B12. Now, the cobalamin is methylcobalamin. The tetrahydrofolate is free, and it can participate in DNA synthesis through a pathway that we will discuss later. But for now, the methylcobalamin, in order for it to participate in DNA synthesis, has to get rid of that methyl group, so it gives it to homocysteine. Homocysteine plus methyl equals methionine. Thank you. The enzyme is homocysteine synthase. Fine. That's why in B12 deficiency or folate deficiency, we have homocysteinemia, because there is no folate to give the methyl to that B12 to give the methyl to the homocysteine to be methionine. So in homocysteinemia, usually the homocysteine levels are increased; methionine levels are decreased.
So now for the tetrahydrofolate story. Tetrahydrofolate will be converted into methylenetetrahydrofolate, not methyl, methylenetetrahydrofolate. That methylenetetrahydrofolate will be converted into dihydrofolate, and at the same step that dUMP is converted into dTMP, and this dTMP, of course, is part of your nice DNA. This thymidylate synthase step is inhibited by a drug called 5-fluorouracil. The dihydrofolate now can be converted back to the tetrahydrofolate to complete the cycle. This enzyme that will reduce the dihydrofolate into tetrahydrofolate is named dihydrofolate reductase. There are drugs that inhibit this dihydrofolate reductase; these are methotrexate and trimethoprim. Please memorize this slide; it's crucial.
Now for the causes of folate deficiency: decreased intake, such as what? Infants, elderly due to malnutrition, alcoholics, and also maybe goat milk. Now, absorption, such as celiac disease. Drug inhibition by 5-fluorouracil, TMP-SMX, and methotrexate, also phenytoin and alcohol and oral contraceptive pills—all of these drugs were in the previous slide. Increased utilization, as pregnancy, lactation, disseminated malignancy, as well as hemolytic anemia. The result: impaired DNA synthesis. As you know, in effect, of not just erythropoiesis but hematopoiesis. This is called what? Pancytopenia. Decreased RBC count, white blood cell count, and blood platelets. Clinically, the same exact symptoms as any anemia. However, bleeding and infection can be present. Why? Less platelets, less white blood cells—pancytopenia. The lab results: hemoglobin and hematocrit decrease—that's the definition of anemia. MCV increased—that's a macrocytic anemia. White blood cell count may be decreased; platelets may be decreased. Why is that? Pancytopenia. Serum folate decrease. RBC folic acid is decreased—this is a more sensitive test. The RBC peripherals may will have macro-ovalocytes, i.e., large RBCs. Do you want to know why? Go to my previous video on the introduction of macrocytic anemia. Hypersegmented neutrophils, which means five or more lobes. So more than five lobes is hypersegmented neutrophils. It has to be more than five lobes in five percent of neutrophils. So at least five lobes in at least five percent of the neutrophils. Also, you can have pancytopenia on your peripheral smear.
What's the treatment of this folate deficiency? Daily oral monoglutamic folate. Please keep in mind folate deficiency is the most common cause of increased serum homocysteine levels. Keep in mind as well the liver contains about three to four months of folic acid supply. After four months, you can become deficient. Note that maybe if you give folic acid to a folate deficiency case, it will improve, of course you know that, but even if you give folate to B12 deficiency, it can improve, but only the symptoms of anemia will improve; the neurological symptoms will not improve. That's why diagnosis is important. Bear with me. Neurological symptoms are not present in folate deficiency; neurological symptoms are only with B12 deficiency.
Question of the day: What are the complications of homocysteinemia? Let me know in the comments. This is our eleventh question. To get all of my questions, you can watch my previous video or go to my Facebook page. Thank you very much. Seeing you in the next video. Study hard.