{"id":5225,"date":"2021-05-13T12:29:51","date_gmt":"2021-05-13T10:29:51","guid":{"rendered":"https:\/\/meddists.com\/learn\/clinical\/hematology\/megaloblastic-anemia-vitamin-b12-and-folic-acid-deficiency\/"},"modified":"2021-05-24T17:03:19","modified_gmt":"2021-05-24T15:03:19","slug":"megaloblastic-anemia-vitamin-b12-and-folic-acid-deficiency","status":"publish","type":"page","link":"https:\/\/meddists.com\/learn\/clinical\/internal-medicine\/hematology\/anemias\/megaloblastic-anemia-vitamin-b12-and-folic-acid-deficiency\/","title":{"rendered":"Megaloblastic anemia (vitamin B12 and folic acid deficiency)"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\">Folic acid and vitamin B12 are required for DNA synthesis.<\/p>\n\n\n<span class=\"block-heading\" id=\"header_1\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Pathophysiology<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_1\">\n\n\n<ul class=\"wp-block-list\"><li><strong>Vitamin B12<\/strong> is a coenzyme for 2 important enzymes responsible for the methylation of DNA, and production of succinyl-CoA.<ul><li>Its absorption requires <strong>intrinsic factor<\/strong> produced by the parietal cells of the stomach.<\/li><li>In healthy individuals, stored vitamin B12 can last for up to 2 years before deficiency develops.<\/li><\/ul><\/li><li><strong>Folate <\/strong>is used for a variety of processes such as single\u2010carbon&nbsp;reactions, amino acid conversion, and synthesis of purines.<\/li><li>Folic acid\/vitamin B12 deficiency leads to<strong>&nbsp;megaloblastic (macrocytic) anemia<\/strong><ul><li>Folic acid deficiency during pregnancy may lead to neural tube defects<\/li><\/ul><ul><li>Vitamin B12 deficiency can cause CNS disturbances<\/li><\/ul><\/li><li>Folic acid analogs such as methotrexate inhibit DHFR, an enzyme necessary for DNA synthesis<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_2\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Etiology<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_2\">\n\n\n<ul class=\"wp-block-list\"><li>Most cases of folic acid deficiency typically arise from<strong> inadequate intake<\/strong>, but they can also arise due to:<ul><li>Malabsorption due to IBD, gastrectomy, tapeworms<\/li><li>Excess utilization (pregnancy, lactation, and stressors increasing cellular turnover)<\/li><li>Drugs (AEDs, sulfasalazine)<\/li><li>Liver and heart disease<\/li><\/ul><\/li><li>In non-vegetarians, the cause of vitamin B12 deficiency is almost always due to abnormal absorption:<ul><li><strong>Pernicious anemia<\/strong> (lack of intrinsic factor), the most common cause; caused by autoimmune activity against the gastric mucosa, with the majority of cases showing anti-intrinsic factor antibodies.<ul><li>Lack of intrinsic factors can also be congenital.<\/li><\/ul><\/li><\/ul><ul><li>Malabsorption (as in folic acid)<\/li><li>Insufficient intake (vegetarians)<\/li><\/ul><\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_3\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Clinical presentation<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_3\">\n\n\n<ul class=\"wp-block-list\"><li>Mild jaundice due to the excessive RBC turnover<\/li><li>Glossitis (inflamed, red, and painful tongue) and angular cheilitis (inflammation of the corners of the mouth)<\/li><li>Weight loss and GI symptoms<\/li><li>Skin purpura and pigmentation<\/li><li>Neuropathy affecting mostly the upper limb (severe B12 deficiency)<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_4\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Diagnosis<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_4\">\n\n\n<ul class=\"wp-block-list\"><li>Dietary history<\/li><li>Blood workup and chemistry (elevated unconjugated bilirubin)<\/li><li>Blood smear (demonstrating macrocytic cells, MCV>98fL, but the size can be normal in coexisting iron deficiency; hypersegmented neutrophils)<\/li><li>Bone marrow sample<ul><li>Hypercellular, increased mitosis.<\/li><li>Many megaloblastic erythroid progenitors with immature nucleus compared to the cytoplasm (megaloblasts, not found in the periphery), giant metamyelocytes, giant band cells, and large and hyperlobulated megakaryocytes.<\/li><\/ul><ul><li>Increased iron stores (can be visualized using Perl&#8217;s Prussian blue).<\/li><\/ul><\/li><li>Quantifying vitamin B12 and folate essays<\/li><li>Methylmalonic acid (B12) and homocysteine (B12+folate) levels, however, these tests are unspecific<\/li><li>Tests for malabsorption (intrinsic factor levels and antibodies, anti-transglutaminase, endoscopy and colonoscopy, biopsy)<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_5\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Treatment<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_5\">\n\n\n<ul class=\"wp-block-list\"><li>Folic acid supplementation is given PO.<\/li><li>Vitamin B12 supplementation is given PO or IM (hydroxocobalamin).<\/li><li>Increased folic acid intake can help make up for vitamin B12 deficiency-induced anemia, but it may worsen neurologic symptoms associated with the deficiency.<\/li><li>Prophylactic supplementation should be given to patients undergoing gastrectomy and ileal resections; folate supplementation should be given to women prior to pregnancy and throughout it.<\/li><\/ul>\n<\/span><div id=\"the_titles\" style=\"display:none;\"><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Pathophysiology<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Etiology<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Clinical presentation<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Diagnosis<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Treatment<\/h4><\/div>","protected":false},"excerpt":{"rendered":"<p>Folic acid and vitamin B12 are required for DNA synthesis. Pathophysiology Vitamin B12 is a coenzyme for 2 important enzymes responsible for the methylation of DNA, and production of succinyl-CoA. Its absorption requires intrinsic factor produced by the parietal cells of the stomach. In healthy individuals, stored vitamin B12 can last for up to 2 [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":5221,"menu_order":1,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-5225","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.9 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Megaloblastic anemia (vitamin B12 and folic acid deficiency) &#8211; Meddists<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/meddists.com\/learn\/clinical\/internal-medicine\/hematology\/anemias\/megaloblastic-anemia-vitamin-b12-and-folic-acid-deficiency\/\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/meddists.com\\\/learn\\\/clinical\\\/internal-medicine\\\/hematology\\\/anemias\\\/megaloblastic-anemia-vitamin-b12-and-folic-acid-deficiency\\\/\",\"url\":\"https:\\\/\\\/meddists.com\\\/learn\\\/clinical\\\/internal-medicine\\\/hematology\\\/anemias\\\/megaloblastic-anemia-vitamin-b12-and-folic-acid-deficiency\\\/\",\"name\":\"Megaloblastic anemia (vitamin B12 and folic acid deficiency) &#8211; 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