Weatherly's Woes - Macrocytic Anemia

Macrocytic Anemia

Macro- (big) -cytic (cells)

In Macrocytic Anemia there are fewer red blood cells, but each RBC is large. The vast majority of macrocytic anemia is caused by a deficiency of either B12 or Folate. As a rule, macrocytic anemias are usually due to an interruption of DNA synthesis (while microcytic anemias were due to an interruption of hemoglobin synthesis).

Let me first address a point about terminology. Megaloblastic Anemia refers to a subtype of macrocytic anemia where the neutrophils have extra lobes (more than 5-6). The vast majority of macrocytic anemias are also megaloblastic, so sometimes the two terms are used interchangeably. Both B12 and Folate Deficiency fall into this category.

So now let’s talk about the findings in megaloblastic anemia.

There are big RBCs. Without the ingredients for new nucleic acid (folate, B12), the body can’t make new DNA. The S phase of the cell cycle stalls. So replicating cells (like an erythroblast) end up going through less cycles of division than usual. Each additional division makes the RBCs smaller. Less DNA = less division = bigger cells.

For reasons beyond my understanding, when the S phase is impaired in maturing neutrophils, it causes their nucleus to grow extra lobes, which are accurately called hypersegmented neutrophils (≥5 lobes). Neutrophils normally have 3 lobes.

RBCs and WBCs are affected because they constantly proliferate. Other proliferative tissues are affected as well, like the gut lining and skin. The tongue’s epithelium is a good example. Replication errors result in glossitis, the inflammation of the tongue that is seen in B12 deficiency and folate deficiency.

Hypersegmented Neutrophil

B12 DEFICIENCY

Craving cobalamin

B12 Deficiency is one of the most common causes of macrocytic anemias. Vitamin B12, aka cobalamin, is the largest B vitamin. It gets the name cobalamin because there is a cobalt molecule in the center. B12 comes from animal products (meat, eggs), so vegans are at risk for developing a B12 deficiency; however, it takes a loooong time (about a decade) to develop a deficiency because the liver keeps huge stores of B12.

The Roles of B12

B12 is needed to turn folate into nucleic acids. Without DNA precursors, cell replication slows down in replicating populations like the RBCs (anemia) and mucus membranes (glossitis).
B12 also metabolizes methylmalonic acid, breaking down odd chain fatty acids. Fatty acids are obviously found in myelin, so B12 deficiency can lead to a pattern of neurological damage called Subacute Combined Degeneration (Spastic paralysis, Cerebellar ataxia, Dorsal column damage). In the elderly, it can cause dementia (one of the rare reversible causes of dementia).

The Causes of B12 Deficiency

Pernicious Anemia is the most common cause of B12 deficiency. Pernicious anemia is an autoimmune disease that attacks the stomach’s acid-producing Parietal cells (which are Pink colored cells in the Peptic environment that have Proton Pumps). In addition to making stomach acid, the parietal cells also make a molecule called intrinsic factor, which is required to absorb B12.

Other causes of B12 Anemia include a strict long-term vegan diet, pancreatic insufficiency (because the proteins that cleave the R-binder are made in the pancreas) and terminal ileum damage (surgical excision, Crohn’s disease or the parasitic fish tapeworm Diphyllobothrium latum).

Treatment of B12 Deficiency

Give B12 Supplement.

FOLATE DEFICIENCY

Fol(ium)- (leaf) -ate (derived from)

Folate Deficiency is the other macrocytic anemia. Folate is also known as Vitamin B9.

Absorption of Folate

Folate shares a root word with ‘foliage’ because folic acid is found in fruits and vegetables (especially leafy green vegetables). Unlike B12, folate isn’t stored for a long time in the body. Folate is absorbed in the Jejunum

Role of Folate

Folate is used to make nucleic acids. Without DNA precursors, cell replication can’t occur, and anemia ensues.

Causes of Folate Deficiency

Poor diet, classically in alcoholics and the elderly.
Increased cell turnover. This occurs when there is something growing in the body (pregnancy or cancer) or there is rapid turnover of cells (hemolytic anemia).
Drugs. Methotrexate inhibits DHF-Reductase (an enzyme involved in the metabolism of Folate).

Findings of Folate Deficiency

NORMAL NEUROLOGICAL EXAM (unlike B12)
Normal methylmalonic acid (which rules out B12 deficiency)
Low serum folate
Anemia with macrocytic RBCs and hypersegmented neutrophils
Glossitis sometimes
Folate deficiency is common in utero. It can lead to neural tube defects (e.g., spina bifida) in the fetus. Prevent with prenatal vitamins.

Folate is found in leafy greens