Professional Documents
Culture Documents
Contents
Causes
Pathophysiology
Diagnosis
Blood findings
See also
References
External links
Causes
Vitamin B12 deficiency:
Achlorhydria-induced malabsorption
Deficient intake
Deficient intrinsic factor, a molecule produced by cells in the stomach that is required for B12 absorption
(pernicious anemia or gastrectomy)
Coeliac disease
Biological competition for vitamin B12 by diverticulosis, fistula, intestinal anastomosis, or infection by the
marine parasite Diphyllobothrium latum (fish tapeworm)
Selective vitamin B12 malabsorption (congenital—juvenile megaloblastic anemia 1—and drug-induced)
Chronic pancreatitis
Ileal resection and bypass
Nitrous oxide anesthesia (usually requires repeated instances).
Folate deficiency:
Alcoholism
Deficient intake
Increased needs: pregnancy, infant, rapid cellular proliferation, and cirrhosis
Malabsorption (congenital and drug-induced)
Intestinal and jejunal resection
(indirect) Deficient thiamine and factors (e.g., enzymes) responsible for abnormal folate metabolism.
Combined Deficiency: vitamin B12 & folate.
Inherited Pyrimidine Synthesis Disorders: Orotic aciduria
Inherited DNA Synthesis Disorders
Toxins and Drugs:
Pathophysiology
There is a defect in DNA synthesis in the rapidly dividing cells and to a lesser extent, RNA and protein synthesis are also
impaired Therefore, unbalanced cell proliferation and impaired cell division occur as a result of arrested nuclear maturation so the
cells show nuclear-cytoplasmic asynchrony.
In the bone marrow, most megaloblasts are destroyed prior to entering the peripheral blood (intramedullary hemolysis) some can
escape the bone marrow (macrocytes) to peripheral blood but they are destroyed by the reticulo-endothelial system
(extramedullary hemolysis).
Diagnosis
The gold standard for the diagnosis of Vitamin B12 deficiency is a low blood level of Vitamin B12. A low level of blood Vitamin
B12 is a finding that normally can and should be treated by injections, supplementation, or dietary or lifestyle advice, but it is not
a diagnosis. Hypovitaminosis B12 can result from a number of mechanisms, including those listed above. For determination of
cause, further patient history, testing, and empirical therapy may be clinically indicated.
A measurement of methylmalonic acid (methylmalonate) can provide an indirect method for partially differentiating Vitamin B12
and folate deficiencies. The level of methylmalonic acid is not elevated in folic acid deficiency. Direct measurement of blood
cobalamin remains the gold standard because the test for elevated methylmalonic acid is not specific enough. Vitamin B12 is one
necessary prosthetic group to the enzyme methylmalonyl-coenzyme A mutase. Vitamin B12 deficiency is but one among the
conditions that can lead to dysfunction of this enzyme and a buildup of its substrate, methylmalonic acid, the elevated level of
which can be detected in the urine and blood.
Due to the lack of available radioactive Vitamin B12, the Schilling test is now largely a historical artifact. The Schilling test was
performed in the past to help determine the nature of the vitamin B12 deficiency. An advantage of the Schilling test was that it
often included Vitamin B12 with intrinsic factor.
Blood findings
The blood film can point towards vitamin deficiency:
An increased lactic acid dehydrogenase (LDH) level. The isozyme is LDH-2 which is typical of the serum and
hematopoetic cells.
Increased homocysteine and methylmalonic acid in Vitamin B12 deficiency
Increased homocysteine in folate deficiency
Normal levels of both methylmalonic acid and total homocysteine rule out clinically significant cobalamin deficiency with virtual
certainty.[6]
Bone marrow (not normally checked in a patient suspected of megaloblastic anemia) shows megaloblastic hyperplasia.[7]
See also
List of circulatory system conditions
List of hematologic conditions
References
1. "Megaloblastic Anemia: Overview - eMedicine Hematology" (http://emedicine.medscape.com/article/204066-over
view). Retrieved 2009-02-07.
2. Berkowitz, Arnold. "M.D." (http://www.healio.com/hematology-oncology/hematologic-malignancies/news/print/he
matology-oncology/%7B9FDEC553-9EA3-4C38-A4A0-59B1CD4BCCA2%7D/Check-the-mouths-of-patients-with-
low-risk-myelodysplasia) Oncologist. Oncology News. Retrieved 2012-07-13.
3. "Megaloblastic (Pernicious) Anemia - Lucile Packard Children's Hospital" (http://www.lpch.org/DiseaseHealthInfo/
HealthLibrary/hematology/megalob.html). Retrieved 2008-03-12.
4. Bain, Barbara J.; Bates, Imelda; Laffan, Mike A. (2016-08-11). Dacie and Lewis Practical Haematology E-Book (h
ttps://books.google.com/books?id=rEPUDAAAQBAJ&pg=PA85). Elsevier Health Sciences.
ISBN 9780702069253.
5. "Megaloblastic Anemia" (https://web.archive.org/web/20121130153546/https://www.nlm.nih.gov/medlineplus/enc
y/article/000567.htm). MedlinePlus. 2012. Archived from the original (https://www.nlm.nih.gov/medlineplus/ency/a
rticle/000567.htm) on 30 November 2012. Retrieved 21 June 2015. "Megaloblastic anemia is a blood disorder in
which there is anemia with larger-than-normal red blood cells. Anemia is a condition in which the body does not
have enough healthy red blood cells. Red blood cells provide oxygen to body tissues."
6. Savage DG, Lindenbaum J, Stabler SP, Allen RH (1994). "Sensitivity of serum methylmalonic acid and total
homocysteine determinations for diagnosing cobalamin and folate deficiencies". Am. J. Med. 96 (3): 239–46.
doi:10.1016/0002-9343(94)90149-X (https://doi.org/10.1016%2F0002-9343%2894%2990149-X). PMID 8154512
(https://www.ncbi.nlm.nih.gov/pubmed/8154512).
7. Hoffbrand, A. Victor (2012). "Chapter 105. Megaloblastic Anemias" (http://accessmedicine.mhmedical.com/conte
nt.aspx?bookid=331&Sectionid=40726843). In Longo, D. L.; Fauci, A. S.; Kasper, D. L.; Hauser SL, S. L.; et al.
(eds.). Harrison's Principles of Internal Medicine (18th ed.). New York: McGraw-Hill. Retrieved October 23, 2015.
External links
GeneReview/NCBI/NIH/UW entry on Thiamine-Responsive
Classification ICD-10: D51.1 (htt D
Megaloblastic Anemia Syndrome (https://www.ncbi.nlm.nih.gov/booksh
elf/br.fcgi?book=gene&part=trma) p://apps.who.int/cla
Rare Anemias Foundation (http://www.rareanemias.webs.com) ssifications/icd10/br
owse/2016/en#/D5
1.1), D52.0 (http://a
pps.who.int/classific
ations/icd10/brows
e/2016/en#/D52.0),
D53.1 (http://apps.w
ho.int/classification
s/icd10/browse/201
6/en#/D53.1) · ICD-
9-CM: 281 (http://w
ww.icd9data.com/g
etICD9Code.ashx?i
cd9=281) · MeSH:
D000749 (https://w
ww.nlm.nih.gov/cgi/
mesh/2015/MB_cg
i?field=uid&term=D
000749) ·
DiseasesDB:
29507 (http://www.d
iseasesdatabase.co
m/ddb29507.htm)
External MedlinePlus:
resources 000567 (https://ww
w.nlm.nih.gov/medli
neplus/ency/article/
000567.htm) ·
eMedicine:
med/1420 (https://e
medicine.medscap
e.com/med/1420-ov
erview) ped/2575 (h
ttp://www.emedicin
e.com/ped/topic257
5.htm#)
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