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Megaloblastic anemia
 
 
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Megaloblastic anemia is an anemia
Anemia

Anemia or an?mia/anaemia is defined as a qualitative or quantitative deficiency of hemoglobin, a protein found inside red blood cells ....
 (of macrocytic
Macrocytic anaemia

Macrocytic is from Greek words meaning "large cell." A macrocytic class of anemia is an anemia in which the erythrocytes are larger than their normal volume....
 classification) which results from inhibition of DNA synthesis
DNA synthesis

DNA synthesis commonly refers to:*DNA replication - DNA biosynthesis *Polymerase chain reaction - enzymatic DNA synthesis *Oligonucleotide synthesis - chemical synthesis of nucleic acids...
 in red blood cell production. This is often due to deficiency of vitamin B
Vitamin B12

Vitamin B12 is a water soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood....
 and/or folic acid
Folic acid

Folic acid and Folate are forms of the water-soluble B vitamins. Vitamin B9 is essential to numerous bodily functions ranging from nucleotide synthesis to the remethylation of homocysteine....
. Megaloblastic anemia not due to hypovitaminosis may be caused by antimetabolites which poison DNA production, such as some chemotherapeutic or antimicrobial agents (for example azathioprine
Azathioprine

Azathioprine is an immunosuppressant used in organ transplantation, autoimmune disease such as rheumatoid arthritis and pemphigus or inflammatory bowel disease such as Crohn's disease and ulcerative colitis as well as multiple sclerosis....
 or trimethoprim
Trimethoprim

Trimethoprim is a bacteriostatic antibiotic mainly used in the prophylaxis and treatment of urinary tract infections. It belongs to the class of chemotherapy agents known as dihydrofolate reductase inhibitors....
).

It is characterized by many large immature and dysfunctional red blood cells (megaloblasts) in the bone marrow, and also by hypersegmented
Hypersegmented neutrophil

A hypersegmented neutrophil is a clinical laboratory finding. It is visualized by drawing blood from a patient and viewing the blood smeared on a microscope slide under a microscope....
 or multisegmented neutrophils.












blood film
Blood film

A blood film or peripheral blood smear is a microscope slide made from a drop of blood, that allows the cells to be examined microscopically....
 can point towards vitamin deficiency:
Blood chemistries will also show: Normal levels of both methylmalonic acid and total homocysteine rule out clinically significant cobalamin deficiency with virtual certainty.






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Encyclopedia


Megaloblastic anemia is an anemia
Anemia

Anemia or an?mia/anaemia is defined as a qualitative or quantitative deficiency of hemoglobin, a protein found inside red blood cells ....
 (of macrocytic
Macrocytic anaemia

Macrocytic is from Greek words meaning "large cell." A macrocytic class of anemia is an anemia in which the erythrocytes are larger than their normal volume....
 classification) which results from inhibition of DNA synthesis
DNA synthesis

DNA synthesis commonly refers to:*DNA replication - DNA biosynthesis *Polymerase chain reaction - enzymatic DNA synthesis *Oligonucleotide synthesis - chemical synthesis of nucleic acids...
 in red blood cell production. This is often due to deficiency of vitamin B
Vitamin B12

Vitamin B12 is a water soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood....
 and/or folic acid
Folic acid

Folic acid and Folate are forms of the water-soluble B vitamins. Vitamin B9 is essential to numerous bodily functions ranging from nucleotide synthesis to the remethylation of homocysteine....
. Megaloblastic anemia not due to hypovitaminosis may be caused by antimetabolites which poison DNA production, such as some chemotherapeutic or antimicrobial agents (for example azathioprine
Azathioprine

Azathioprine is an immunosuppressant used in organ transplantation, autoimmune disease such as rheumatoid arthritis and pemphigus or inflammatory bowel disease such as Crohn's disease and ulcerative colitis as well as multiple sclerosis....
 or trimethoprim
Trimethoprim

Trimethoprim is a bacteriostatic antibiotic mainly used in the prophylaxis and treatment of urinary tract infections. It belongs to the class of chemotherapy agents known as dihydrofolate reductase inhibitors....
).

It is characterized by many large immature and dysfunctional red blood cells (megaloblasts) in the bone marrow, and also by hypersegmented
Hypersegmented neutrophil

A hypersegmented neutrophil is a clinical laboratory finding. It is visualized by drawing blood from a patient and viewing the blood smeared on a microscope slide under a microscope....
 or multisegmented neutrophils.

Causes

  • Vitamin B12 deficiency
    Vitamin B12 deficiency

    B12 deficiency is a reduction in vitamin B12 from inadequate dietary intake or impaired absorption. The condition is commonly asymptomatic, but can also present as anemia characterized by enlarged blood corpuscles, so-called megaloblastic anemia....
    :
    • achlorhydria
      Achlorhydria

      Achlorhydria and hypochlorhydria refer to states where the production of gastric acid in the stomach is absent or low, respectively. It is associated with various other medical problems....
      -induced malabsorption
    • Deficient intake
    • Deficient intrinsic factor (pernicious anaemia or gastrectomy
      Gastrectomy

      A gastrectomy is a partial or full surgical removal of the stomach....
      )
    • Biological competition for B12 by diverticulosis
      Diverticulosis

      Diverticulosis, otherwise known as "diverticular disease", is the condition of having diverticulum in the colon which are outpocketings of the colonic mucosa and submucosa through weaknesses of muscle layers in the colon wall....
      , fistula
      Fistula

      In medicine, a fistula is an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect....
      , intestinal anastomosis
      Anastomosis

      An anastomosis is a network of streams that both branch out and reconnect, such as blood vessels or leaf veins. The term is used in medicine, biology, mycology and geology....
      , and infection by the marine parasite Diphyllobothrium latum
    • Selective B12 malabsorption (congenital and drug-induced)
    • Chronic pancreatitis
      Chronic pancreatitis

      Chronic pancreatitis is a long-standing inflammation of the pancreas that alters its normal structure and functions. It can present as episodes of acute inflammation in a previously injured pancreas, or as chronic damage with persistent pain or malabsorption....
    • Ileal resection and bypass
    • Nitrous oxyde anaesthesis


  • Folate deficiency
    Folate deficiency

    Signs of folic acid deficiency are often subtle....
    :
    • alcoholism
      Alcoholism

      Alcoholism is a term with multiple and sometimes conflicting definitions to describe the detrimental effects of alcohol intake.In common and historic usage, alcoholism refers to any condition that results in the continued consumption of alcoholic beverages despite health problems and negative social consequences....
    • Deficient intake.
    • Increased needs: pregnancy
      Pregnancy

      Pregnancy is the carrying of one or more offspring, known as a fetus or embryo, inside the uterus of a female. In a pregnancy, there can be multiple gestations, as in the case of twins or Multiple birth....
      , infant
      Infant

      An infant or baby is the term used to refer to the young offspring of humans....
      , rapid cellular proliferation, and cirrhosis
      Cirrhosis

      Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver Tissue by fibrous scar tissue as well as regenerative Nodule , leading to progressive loss of liver function....
    • Malabsorption (congenital and drug-induced)
    • Intestinal and jujenal resection


  • Combined Deficiency (Tropical sprue
    Tropical sprue

    Tropical sprue is a malabsorption disease commonly found in the tropical regions, marked with abnormal flattening of the villi and inflammation of the lining of the small intestine....
    ): Vitamin B12 & Folate.


  • Inherited DNA
    DNA

    Deoxyribonucleic acid is a nucleic acid that contains the genetics instructions used in the development and functioning of all known living organisms and some viruses....
     Synthesis Disorders: Deficient thiamine
    Thiamine

    'Thiamine', or 'thiamin', sometimes called aneurin, is a water-soluble vitamin of the B complex , whose phosphate derivatives are involved in many cellular processes....
     and factors (e.g. enzymes) responsible for folate metabolism.


  • Toxins and Drugs:
    • Folic acid
      Folic acid

      Folic acid and Folate are forms of the water-soluble B vitamins. Vitamin B9 is essential to numerous bodily functions ranging from nucleotide synthesis to the remethylation of homocysteine....
       antagonists (methotrexate
      Methotrexate

      Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug used in treatment of cancer and autoimmune diseases....
      )
    • Purine
      Purine

      Purine is a heterocyclic compound aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
       synthesis antagonists (6-mercaptopurine)
    • Pyrimidine
      Pyrimidine

      Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring....
       antagonists (cytosine arabinoside)


  • Erythroleukemia
    Erythroleukemia

    Acute erythroid leukemia is a rare form of acute myeloid leukemia where the myeloproliferation is of erythroblastic precursors.It is defined at type "M6" under the Acute myelogenous leukemia#French-American-British .28FAB.29 classification....


Hematological findings

The blood film
Blood film

A blood film or peripheral blood smear is a microscope slide made from a drop of blood, that allows the cells to be examined microscopically....
 can point towards vitamin deficiency:
  • Decreased red blood cell
    Red blood cell

    Red blood cells are the most common type of blood cell and the vertebrate body's principal means of delivering oxygen to the body tissues via the blood....
     (RBC) count and hemoglobin
    Hemoglobin

    Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of vertebrates, and the tissues of some invertebrates....
     levels
  • Increased mean corpuscular volume
    Mean corpuscular volume

    The mean corpuscular volume, or MCV, is a measure of the average red blood cell volume that is reported as part of a standard complete blood count....
     (MCV, >95 fl) and mean corpuscular hemoglobin
    Mean corpuscular hemoglobin

    The mean corpuscular hemoglobin, or "mean cell hemoglobin" , is the average mass of hemoglobin per red blood cell in a sample of blood. It is reported as part of a standard complete blood count....
     (MCH)
  • The reticulocyte
    Reticulocyte

    Reticulocytes are immature red blood cells, typically composing about 1% of the red cells in the human body.Reticulocytes develop and mature in the red bone marrow and then circulate for about a day in the blood stream before developing into mature red blood cells....
     count is decreased due to destruction of fragile and abnormal megaloblastic erythroid precursor.
  • The platelet
    Platelet

    Platelets, or Thrombocyte, are small, irregularly shaped anuclear cells, 2-4?m in diameter, which are derived from fragmentation of precursor megakaryocytes....
     count may be reduced.
  • Neutrophil granulocyte
    Neutrophil granulocyte

    Neutrophil granulocytes, generally referred to as neutrophils, are the most abundant type of white blood cells in humans and form an essential part of the immune system....
    s may show multisegmented nuclei ("senile neutrophil"). This is thought to be due to decreased production and a compensatory prolonged lifespan for circulating neutrophils, which increase numbers of nuclear segments with age.
  • Anisocytosis
    Anisocytosis

    Anisocytosis is a medical term meaning that a patient's red blood cells are of unequal size. This is found in anemia and other blood conditions....
     (increased variation in RBC size) and poikilocytosis
    Poikilocytosis

    Poikilocytosis refers to the presence in the blood of poikilocytes. Poikilocytes are abnormally shaped red blood cells as seen on a blood film in humans and many wild and domestic species of animals, though they are common in some clinically normal small ruminants, particularly goats....
     (abnormally shaped RBCs).
  • Macrocytes (larger than normal RBCs) are present.
  • Ovalocytes (oval-shaped RBCs) are present.
  • Howell-Jolly bodies
    Howell-Jolly body

    Howell-Jolly bodies are histopathology findings of basophilic nuclear remnants in circulating erythrocytes. During maturation in the bone marrow erythrocytes normally expel their nuclei, but in some cases a small portion of DNA remains....
     (chromosomal remnant) also present.

Blood chemistries will also show:
  • Increased homocysteine and methylmalonic acid in B deficiency
  • Increased homocysteine in folate defiency
Normal levels of both methylmalonic acid and total homocysteine rule out clinically significant cobalamin deficiency with virtual certainty.


Bone marrow
Bone marrow

Bone marrow is the flexible biological tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells....
 (not normally checked in a patient suspected of megaloblastic anemia) shows megaloblastic hyperplasia
Hyperplasia

Hyperplasia is a general term referring to the proliferation of cells within an organ or tissue beyond that which is ordinarily seen . Hyperplasia may result in the gross enlargement of an organ, the formation of a benign tumor, or may be visible only histology....
.

Possible associated neurological findings

Subacute combined degeneration of spinal cord
Subacute combined degeneration of spinal cord

Subacute combined degeneration of spinal cord, also known as Ludwig Lichtheim's disease, refers to degeneration of the posterior and lateral columns of the spinal cord as a result of vitamin B12 deficiency....
 and its symptoms may be present, due to demyelination secondary to deficiency of vitamin B.

Analysis

The gold standard for the diagnosis of B deficiency is a low blood level of B. A low level of blood B is a symptom which normally can and should be treated by injections, supplementation, or dietary or lifestyle advice, but it is not a diagnosis. Hypovitaminosis B can result from a number of mechanisms, including those listed above. For determination of etiology, further patient history, testing, and empirical therapy may be clinically indicated.

A measurement of methylmalonic acid can provide an indirect method for partially differentiating B12 and folate deficiencies. The level of methylmalonic acid is not elevated in folic acid deficiency. But direct measurement of blood cobalamin remains the gold standard because the test for elevated methylmalonic acid is not specific enough. Vitamin B is one necessary prosthetic group to the enzyme methylmalonyl-coenzyme A mutase. B deficiency is but one among the conditions that can lead to dysfunction of this enzyme and a buildup of its substrate, methylmalonic acid
Methylmalonic acid

Methylmalonic acid is a dicarboxylic acid that is a C-Methylation derivative of malonate....
, the elevated level of which can be detected in the urine and blood.

Due to the lack of available radioactive B, the Schilling test
Schilling test

The Schilling's test is a medical investigation used in patients with vitamin B12 deficiency. The purpose of the test is to determine if the patient has pernicious anemia....
 is now largely a historical artifact. The Schilling test
Schilling test

The Schilling's test is a medical investigation used in patients with vitamin B12 deficiency. The purpose of the test is to determine if the patient has pernicious anemia....
 was performed in the past to help determine the nature of the vitamin B deficiency. An advantage of the Schilling test
Schilling test

The Schilling's test is a medical investigation used in patients with vitamin B12 deficiency. The purpose of the test is to determine if the patient has pernicious anemia....
 was that it often included B with intrinsic factor.