Vitamin B12 metabolism
Vitamin B12 can be acquired from animal products (so vegans need to take care to get enough vitamin B12). We only need around 1μg of B12 per day, but our body can store 2-4mg, so we essentially have several years' worth of B12 supply. Therefore, a deficiency in B12 can take years to manifest.
Absorption of Vitamin B12 requires intrinsic factor, which is secreted by parietal cells in the stomach. However, Vitamin B12 doesn't bind to intrinsic factor until later. Instead, in the stomach, B12 binds to R-binder, which protects it from stomach acid. B12 is later released from R-binder by the action of pancreatic enzymes in the duodenum. Further down the duodenum and jejunum, B12 finally binds to intrinsic factor. In the ileum, B12 bound to intrinsic factor is absorbed into the body. Once in the body, active B12 is bound to transcobalamin II, and inactive B12 is bound to transcobalamin I. Active B12 and transcobalamin II levels can be measured by using the HoloTransCobalamin assay.
Vitamin B12 is mainly used in two reactions. The first main reaction involving B12 is the conversion of homocysteine to methionine, which is important in methylation in DNA, RNA, and proteins. The second main reaction involving B12 is the conversion of methylmalonyl CoA to succinyl CoA, which is important in breaking down fatty acids and amino acids to ATP (succinyl CoA can enter the citric acid cycle).
Folate metabolism
Folate (vitamin B9) can be found in fruits and leafy green vegetables. We require about 100μg per day. Unlike vitamin B12, we do not have years' worth of folate storage: instead, we only have around 3-4 months. Therefore, folate deficiencies crop up much more quickly than B12 deficiencies. Folate is absorbed in the upper GI tract.
Folate is an essential coenzyme in the production of DNA. Folate is reduced to tetrahydrofolate, which is involved in the synthesis of nucleotides. There is also some interplay between folate and vitamin B12, as vitamin B12 can help to recharge inactive folate.
Causes and consequences of deficiencies
Vitamin B12
Vitamin B12 deficiency can be due to inadequate intake (more likely in vegans as B12 is only found in animal products) or malabsorption. The main cause of B12 malabsorption, and the main cause of B12 deficiency in general, is pernicious anaemia. In pernicious anaemia, there are auto-antibodies either to intrinsic factor or to the parietal cells that produce intrinsic factor. Since there is reduced intrinsic factor, there is reduced absorption of B12. Pernicious anaemia is most common in females aged around 60 with a family history of auto-immune disease.
B12 deficiency has gradual onset and as such can be asymptomatic for a long time. However, over time, there can be mild jaundice due to ineffective erythropoiesis (red blood cells need B12 to form properly), or neurological symptoms due to degeneration of the spinal cord. These neurological symptoms may include tingling of the feet or difficulties in walking. B12 deficiency causes megaloblastic anaemia, which I will describe later.
B12 deficiency treatment is simple: simply give IM vitamin B12. Usually 1000μg is given three times per week for two weeks, and then one injection every 3 months until the deficiency is corrected (or for life if the deficiency cannot be corrected). It is also possible to give large doses of oral vitamin B12, but this is less reliable, particularly in patients with pernicious anaemia (if they can't produce enough intrinsic factor, most of that B12 won't be absorbed anyway).
Folate
Folate deficiency may be due to inadequate intake, poor absorption, increased folate requirements (e.g. during pregnancy), or excessive folate loss (as may happen in dialysis). Certain medications and excessive alcohol may also lead to folate deficiency.
As folate is important for DNA and RNA synthesis, it is also important for fetal growth and development (a time when lots of cell division and signalling is going on). Folate deficiency may cause the fetal neural tube to fail to close. Neural tube closure usually happens at around 21-27 days and, depending on the severity of the defect, can lead to a range of problems, from spina bifida (part of the spinal cord bulging out) to anencephaly (loss of most of the brain).
Just like with B12, treatment is fairly straightforward: simply provide folate supplementation. In this case, the amount is 5mg/day until the deficiency is corrected.
Megaloblastic anaemia
Megaloblastic anaemia is a type of macrocytic anaemia, meaning that the red blood cells are larger than normal. Red blood cells are also oval in shape. Neutrophils may be hypersegmented, meaning that their nuclei have a lot of lobes (they usually have 3, but can have 5 or more in a hypersegmented state). The bone marrow tends to be hypercellular: it has lots of cells because the body is trying to produce more red blood cells to counter the anaemia, but they can't develop properly due to the lack of B12 and/or folate. (I think.)
Megaloblastic anaemia results in abnormal erythroblasts in the bone marrow. Haemoglobinisation appears at a normal rate, but maturation of the nucleus is delayed due to impairment in DNA production. Therefore, you might see cells that are reasonably red (due to haemoglobinisation), but still have quite large nuclei (remember, red blood cells get smaller nuclei as they mature, so a large nucleus is a hallmark of an immature cell).
It is also important to note that megaloblastic anaemia is not the only type of anaemia that is macrocytic (has large blood cells). Liver disease, for instance, may also result in macrocytic anaemia. Also, in many cases of anaemia, the body tries to produce more red blood cells, and since the immature ones (e.g. reticulocytes) tend to be larger, the mean cell volume increases. Some of these other macrocytic anaemias may also have specific features. For instance, macrocytic anaemia in liver disease may have target cells (red blood cells that have a dark part in the pale centre) and/or acanthocytes (spiky cells).
No comments:
Post a Comment