Pathology 3500
Pathology 3500
B12 Deficiency
Introduction
Cobalamin, another name for vitamin B12, is a water-soluble vitamin that is necessary for DNA synthesis, neurological function, and the creation of red blood cells. If unchecked, a B12 deficiency can cause severe health issues such as anemia, cognitive decline, and irreparable nerve damage .
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Symptoms
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B12 Physiology
Absorption
In the stomach, vitamin B12 is released from proteins via the use of gastric acid and an enzyme, pepsin. B-12 then binds with haptocorrin (HC) which protects it from the acidic environment in the stomach. Once this complex is in the duodenum, pancreatic enzymes degrade haptocorrin, releasing the B12. B12 then binds to an intrinsic factor, where this B12-IF complex is crucial for final absorption of B12 in the ileum of the small intestine .
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Transportation
After B12 is absorbed in the terminal ileum, B12 enters the bloodstream and binds to transcobalamin II. This holo-transcobalamin complex delivers B12 to various cells, tissues and organs in the body by binding to specific receptors. Once inside the cell through a process called endocytosis, transcobalamin II is degraded within lysosomes, facilitating the release of B12 into the cytoplasm of the cells. In the cytoplasm, B12 is converted to its active forms methylcobalamin and adenosylcobalamin which are important to crucial processes detailed above!
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Storage
The liver is the primary storage site for vitamin B12, maintaining a reserve that can last for several years. The body stores between 1 to 5mg on average! However, other organs also store B12; one of these includes the kidneys, which have a large capacity to store excess B12. This storage capacity ensures a continuous supply of the vitamin during periods of low dietary intake. These reserves of B12 are why B12 deficiency symptoms can take years to manifest .
Usage
B12 is important for the development of small and round red blood cells. A deficiency can result in large and irregularly shaped red blood cells, which can result in anemia. B12 is also important for DNA synthesis or replication, which is important for the maintenance of healthy cells. Nerve health is dependent on B12 as B12 is important to the synthesis of myelin, the protective covering of nerves. This works hand in hand in general brain function, as a deficiency can cause tingling in the hands and feet, memory loss and sometimes mood disorders. B12 is also important for general energy production from the foods we eat, recall the absorption section!
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Clinical Manifestations
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Gastrointestinal manifestations: inflamed tongue, oral ulcers, appetite loss, weight loss, in some cases anorexia, digestive issues .
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Cognitive disturbances: confusion, concentration issues and memory loss .
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Mood Changes: Irritability, depression, and other mood alterations can be associated with B12 deficiency . ​
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Neurological Symptoms: Numbness, tingling, balance issues, memory loss, mood changes, cognitive decline. Many of these symptoms are linked to impaired myelin synthesis .
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Hematological Symptoms: Fatigue, weakness, pale skin, dizziness, shortness of breath, irregular heartbeat or Tachycardia .
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Severe Cases: Permanent nerve damage, paralysis, or dementia-like symptoms if untreated .
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Other Manifestations: Jaundice, Weakened immunity, infertility risks, psychiatric disturbances (hallucinations, paranoia), vision issues .
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Diagnostic Evaluation for a B12 Deficiency
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1. Clinical assessment
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A thorough medical history and physical examination takes place, with a focus on symptoms and manifestations .
2. Lab tests
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CBC (complete blood count): assess for anemia and may show enlarged red blood cells as well .
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Serum Vitamin B12 levels: Measures levels of B12 in the blood. Anything below level 200 pg/ml are qualified as a deficiency .
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Methylmalonic Acid (MMA) and Homocysteine levels: elevated levels of these 2 metabolites can indicate a B12 deficiency, even if serum levels are not alarming .
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Intrinsic factor antibodies: tests for these antibodies can help diagnose pernicious anemia .
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3. Additional Diagnostic Considerations
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If diagnosis remains uncertain, further tests such as a peripheral blood smear or bone marrow biopsy may be done.​
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It's also important to consider dietary habits, gastrointestinal health, and medication use .
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Secondary Complications
Glossitis
Subacute Combined Degeneration (SCD)
Ataxia
Inflammation of the tongue causing it to appear red and smooth
Demyelination of the dorsal and lateral columns of the spinal cord leads to limb weakness and impaired coordination
A drop in physical coordination, which can lead to difficulty speaking
and walking
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Bone Health
Depression and Anxiety
Vision Issues
Lower bone mineral density, which increases the risk of osteoporosis and fractures
A B12 deficiency can not only cause irritability, but can worsen preexisting depression and/or anxiety
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A B12 deficiency can affect
the optic nerve and in
severe cases cause
optic neuropathy
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Treatment and Management
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B12 Replacement therapy
The preferred route for a severe B12 deficiency is an intramuscular injection that can be administered by a pharmacist or family physician. This injection is done once every 2-3 months. For mild cases, a high dose oral supplement can be taken. This route is very convenient and effective. The least effective treatment is a nasal or sublingual option, however is still valuable in mild cases .
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2. Underlying causes
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Changes to one's diet must include an increase in B12 rich foods such as meat, fish, eggs and dairy. Vegans and vegetarians may need fortified foods or a purely supplemental pathway .
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Global Impact
Vitamin B12 deficiency is a global health issue, however, it is more prevalent in low-income populations and countries. Developing countries like India and parts of Africa report prevalence rates as high as 70-80%. Notably, a large number of children suffer from a B12 deficiency in these areas, with a prevalence rate of 21-45%. Factors such as low socioeconomic status and limited intake of foods rich in B12 due to access are linked to a significant number of people suffering with a B12 deficiency. In the US, Canada and UK, 5-20% of individuals are affected, most of which are over the age of 60 .