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'''Macrocytosis''' is the enlargement of [[red blood cell]]s with near-constant [[haemoglobin]] concentration, and is defined by a [[mean corpuscular volume]] (MCV) of greater than 100 femtolitres (the precise criterion varies between laboratories).  
'''Macrocytosis''' is the enlargement of [[red blood cell]]s with near-constant [[haemoglobin]] concentration, and is defined by a [[mean corpuscular volume]] (MCV) of greater than 100 femtolitres (the precise criterion varies between laboratories).  
==Classifcation==
==Classifcation==
'''Megaloblastic anemia''' is an [[anemia]] (of [[macrocytic anaemia|macrocytic]] classification) which results from inhibition of DNA synthesis in red blood cell production. It is often due to deficiency of [[vitamin B12]] and/or [[folic acid]]. It can be the result of a lack of [[intrinsic factor]] (which lack interferes with B12 absorption), causing [[pernicious anemia]], or with other antimetabolites which poison DNA production, such as chemotherapeutic agents. It is characterized by many large immature and dysfunctional red blood cells ([[megaloblasts]]) in the bone marrow, and also by hypersegmented or multisegmented [[neutrophil]]s. <ref>Babior BM, Bunn HF, Megaloblastic Anemias. Harrison’s Principles of Internal Medicine.  13th Ed.  1994: 1726-1732. ISBN 0070323704</ref> <ref>Toh BH, van Driel IR, Gleeson PA.  Mechanisms of Disease: Pernicious Anemia. NEJM 1997;337:1441.</ref>
==Classification==
===Megaloblastic anemias (DNA replication disorders)===
* Commonest cause of macrocytic anemia.
* In [[megaloblastic anemia]]s cells are larger because they cannot produce DNA quickly enough to divide at the right time as they grow, and thus grow too large before division.
* Causes for the DNA synthetic problem range from lack of certain vitamins needed to produce DNA (notably [[folate]] and [[B12]]), to poisons or inhibitors of DNA replication, such as some kinds of antiviral drugs and chemotherapeutic agents.
* The pathognomonic findings of megaloblastic anemia are: megaloblasts in [[bone marrow]], ovalocytes in the (peripheral) blood smear, and hypersegmented [[neutrophils]].
 
===Non megaloblastic macrocytic anemias===
* Non megaloblastic macrocytic anemias, are disorders associated with increased red cell membrane surface area
* It is commonly associated with pathologies of the liver and spleen which produce [[codocyte]]s or "target cells" which have a central collection of hemoglobin surrounded by a pallor (a thin area) then followed by a thicker collection of hemoglobin at the rim of the cell.
 
===Alcohol===
* Round macrocytes which are not codocytes are produced in chronic alcoholism (which produces a mild macrocytosis even in the absence of vitamin deficiency), apparently as a direct toxic effect of alcohol specifically on the bone marrow.
 
===Association with rapid red cell turnover and reticulocytosis===
Mild macrocytocis is a common finding associated with rapid blood restoration or production, since in general, "fresh" or newly-produced red cells ([[reticulocytes]]) are larger than the mean (average) size, due to slow shrinkage of normal cells over a normal red cell circulating lifetime. Thus, [[chronic obstructive pulmonary disease]] (COPD), in which which red cells are rapidly produced in response to low oxygen levels in the blood, often produces mild macrocytosis. Also, rapid blood replacement from the marrow after a traumatic blood loss, or rapid red blood cell turnover from rapid hemolysis, also often produces mild macrocytosis in the associated anemia.


==References==
==References==

Revision as of 14:37, 21 September 2012

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Macrocytosis is the enlargement of red blood cells with near-constant haemoglobin concentration, and is defined by a mean corpuscular volume (MCV) of greater than 100 femtolitres (the precise criterion varies between laboratories).

Classifcation

Classification

Megaloblastic anemias (DNA replication disorders)

  • Commonest cause of macrocytic anemia.
  • In megaloblastic anemias cells are larger because they cannot produce DNA quickly enough to divide at the right time as they grow, and thus grow too large before division.
  • Causes for the DNA synthetic problem range from lack of certain vitamins needed to produce DNA (notably folate and B12), to poisons or inhibitors of DNA replication, such as some kinds of antiviral drugs and chemotherapeutic agents.
  • The pathognomonic findings of megaloblastic anemia are: megaloblasts in bone marrow, ovalocytes in the (peripheral) blood smear, and hypersegmented neutrophils.

Non megaloblastic macrocytic anemias

  • Non megaloblastic macrocytic anemias, are disorders associated with increased red cell membrane surface area
  • It is commonly associated with pathologies of the liver and spleen which produce codocytes or "target cells" which have a central collection of hemoglobin surrounded by a pallor (a thin area) then followed by a thicker collection of hemoglobin at the rim of the cell.

Alcohol

  • Round macrocytes which are not codocytes are produced in chronic alcoholism (which produces a mild macrocytosis even in the absence of vitamin deficiency), apparently as a direct toxic effect of alcohol specifically on the bone marrow.

Association with rapid red cell turnover and reticulocytosis

Mild macrocytocis is a common finding associated with rapid blood restoration or production, since in general, "fresh" or newly-produced red cells (reticulocytes) are larger than the mean (average) size, due to slow shrinkage of normal cells over a normal red cell circulating lifetime. Thus, chronic obstructive pulmonary disease (COPD), in which which red cells are rapidly produced in response to low oxygen levels in the blood, often produces mild macrocytosis. Also, rapid blood replacement from the marrow after a traumatic blood loss, or rapid red blood cell turnover from rapid hemolysis, also often produces mild macrocytosis in the associated anemia.

References

gl:Anemia megaloblástica he:אנמיה מגלובלסטית it:Anemia megaloblastica sl:Megaloblastna anemija sr:Мегалобластна анемија


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