Vitamin B12 Deficiency

Pernicious anaemia (PA), often seen with extreme vitamin B12 deficiency, is a relatively rare, chronic illness caused by impaired absorption of vitamin B12 from the intestine due to a lack of intrinsic factor (IF) (a specific transport protein require for vitamin B12 uptake) in gastric secretions. PA, was the more common form of adult onset anaemia and is associated with gastric atrophy and a loss of IF production, which is different from a rare congenital anaemia recessive form in which IF production is lacking without gastric atrophy. The disease typically does not occur before the age of 30, and when it does the disease can be relatively slow to progress. Generally there are two types of auto-antibodies that are associated with PA, anti-parietal cell antibodies, and anti-IF antibodies. It is important to distinguish between the two forms as the sequelae are somewhat different.

Pernicious anaemia may often be associated with unexplained weight loss of around 10-15 lb (4-7 kg) occurs in about 50% of patients possibly due to anorexia, which is observed in most patients. Low-grade fever occurs in one third of newly diagnosed patients and promptly disappears with treatment.

Iron deficiency is very common in Pernicious anaemia and may precede the vitamin B12 deficiency of Pernicious anemia by as much as 20 years, particularly in females. This is more common if the Pernicious anaemia is due to anti-parietal cell antibodies, as these reduce the production of HCl in the gut and so reduces the ability to digest the iron out of food (Toh, 2017).

Tiredness and fatigue is associated with the anaemia (reduced red cell numbers), which is gradually restored during treatment. However, the cardiac output is usually increased with haematocrit values less than 20%, and the heart rate accelerates. This may in turn lead to congestive heart failure and coronary insufficiency particularly in patients with pre-existing heart disease.

Gastrointestinal Symptoms

Approximately 50% of patients have a smooth tongue with loss of papillae, particularly along the edges of the tongue. The tongue may be painful and beefy red.  Many patients experience burning or soreness, most particularly on the anterior third of the tongue, and may lead to changes in taste and loss of appetite.

Altered bowel movements are common and include constipation or having several semisolid bowel movements daily. These symptoms have been attributed to megaloblastic changes of the cells of the intestinal mucosa. These changes can also be associated with altered uptake of essential nutrients such as B group vitamins.
Non-specific gastrointestinal (GI) symptoms include anorexia, heartburn, nausea, vomiting, heart burn, flatulence, and a sense of fullness.

Neurological Symptoms

Neurological symptoms typical of prolonged vitamin B12 deficiency can be elicited in patients with pernicious anemia. The most common of these are parasthesiae (feeling of pins and needles), weakness, clumsiness, and an unsteady gait. Impaired proprioception is worse in the dark as patients are unable to rely upon vision for compensation. These neurologic symptoms are due to myelin degeneration and loss of nerve fibres in the dorsal and lateral columns of the spinal cord and cerebral cortex.
Symptoms of long term VB12 deficiency can be seen in older patients such as senile dementia, peripheral neuropathy, and psychosis Alzheimer disease; memory loss, irritability, and personality changes delusions, hallucinations, outbursts, and paranoid schizophrenic ideation.

Vitamin B12 deficiency can per se lead to urinary and fecal incontinence due to the neuronal consequences of inadequate VB12. The impaired micturition can predispose patients to urinary tract infections.

Treatment of Pernicious Anemia

Typically patients who are eventually diagnosed with PA are treated by injection with cyanocobalamin or more recently hydroxycobalamin every 4 to 6 weeks for the rest of their lives. During that time they go through "overdose" initially (but without side effects), sufficiency and then deficiency. They are then re-injected with vitamin B12 and the cycle starts again. The tissues of the body have a limited ability to take up VB12 and so the majority of injected doses above 50 ug are rapidly excreted in the urine and hence the depleted stores in the liver and particularly the brain are not replenished. The continual need for re-injection of VB12 is testament to the lack of replenishment throughout the body, as in fully replete individuals, VB12 deficiency normally takes 2-5 years to manifest itself. Whilst hydroxycobalamin has been shown to be more efficient at uptake than cyanocobalamin, several studies have shown that many individuals who are severely deficient in VB12 have limited capacity to fully convert the hydroxycobalamin to Methyl and adenosylcobalamin, particularly if they have hypothyrodism or are functionally deficient in vitamin B2. Persons with PA generally have a higher need for vitamin B12 than those with deficiency due to conditions that do not involve lack of IF, because in IF-mediated B12 deficiency, the lack of IF means that vitamin B12 lost from the circulation via bile or saliva is not re-absorbed.

Recently, a transdermal form of vitamin B12 delivery has been developed with the distinct purpose of over-coming the disadvantage of standard injections, without the associated pain and discomfort experienced during injection. Thus, the device free application of vitamin B12 via the transdermal technology allows a continuous release of low doses of vitamin B12 into the body. The continual trickle of vitamin B12 via the transdermal route greatly reduces the rapid loss of VB12 from the body, which occurs with injectable forms of vitamin B12 and in addition allows for greater priming of the VB12 transport protein, transcobalamin II. This in turn can potentially lead to more efficient replenishment of the liver, tissues and in particular the central nervous system. See b12oils.com

See the following links:-

http://emedicine.medscape.com/article/204930-overview

https://rarediseases.org/rare-diseases/anemia-pernicous/

Toh BH 2017 Pathophysiology and laboratory diagnosis of pernicious anemia https://www.ncbi.nlm.nih.gov/pubmed/27538411

Chang et al 2016 Hematinic deficiencies and anemia statuses.... https://www.ncbi.nlm.nih.gov/pubmed/27511590