Updated: 8/5/2020

B12 Deficiency

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Snapshot
  • A 52-year-old man presents to his physician for a routine check-up. He reports increasing fatigue and has a smooth, sore tongue. He is a strict vegan and has had bariatric surgery 3 years ago. Physical examination is notable for decreased vibration sensation and proprioception. Laboratory studies demonstrate a macrocytic anemia with reticulocytopenia. Peripheral blood smear demonstrates hypersegmented neutrophils.
Introduction
  • Overview
    • vitamin B12 (cobalamin) is a water-soluble vitamin that is involved in the formation of hematopoietic cells and maintainance of myelin integrity
    • vitamin B12 deficiency results in a
      • megaloblastic anemia
      • reversible dementia
      • subacute combined degeneration
  • Etiology
    • decreased oral intake
      • strict vegan diet
      • breastfeeding in a vitamin B12 deficiency mother
      • decreased animal product intake
    • decreased absorption
      • gastrointestinal surgeries
        • bariatric surgery
        • grastrectomy
      • illness
        • Crohn disease
        • celiac disease
        • pancreatic insufficiency
        • Diphyllobothrium latum (fish tapeworm) 
        • gastric atrophy
      • medications
        • proton pump inhibitors
        • histamine receptor antagonist
        • metformin
      • autoimmune disease
        • pernicious anemia
          • autoantibodies against intrinsic factor or gastric parietal cells 
  • Pathophysiology
    • absorption
      • protein-bound vitamin B12 is released from protein by pepsin
        • gastric acid converts pepsinogen to pepsin
      • R-binder binds to vitamin B12 to prevent its degradation by gastric acid
        • R-binder is produced in the salivary glands
      • proteases in the duodenum separate R-binder and vitamin B12, allowing vitamin B12 to bind to intrinsic factor
        • intrinsic factor is produced by gastric parietal cells
          • roux-en-Y gastric bypass creates a small gastric pouch, which contains very few parietal cells
            • reduces acid and intrinsic factor secretion, which impair absorption 
        • proteases in the duodenum are produced by the pancreas
      • intrinsic factor bound to vitamin B12 is absorbed in the terminal ileum
    • DNA synthesis
      • vitamin B12 serves as a coenzyme for methionine synthase to produce
        • methionine
          • serves a vital role in methylation reactions
        • tetrahydrofolate
          • serves a vital role in DNA synthesis
    • myelin stabilization
      • methionine is converted to S-adenosylmethionine
        • associated with myelin stabilization
      • vitamin B12 serves as a coenzyme for methylmalonyl-CoA mutase to convert methylmalonyl-CoA (produced from methylmalonic acid) to succinyl-CoA
        • decreased methylmalonic acid is associated with myelin stabilization
    • vitamin B12 deficiency
      • impaired DNA synthesis significantly affects rapidly dividing cells (e.g., hematopoietic precursor cells) and leads to
        • megaloblastic changes, which is cased by slowing of nuclear division
          • due to nuclear-cytoplasmic dyssynchrony
        • ineffective erythropoiesis (intramedullary hemolysis)
          • erythropoietic precursor cells within the bone marrow prematurely die
            • results in a reticulocytopenia
      • impair neuronal function
        • mechanism is not fully clear but hypothesized to be due to decreased methylation of neuronal lipids and proteins (e.g., myelin basic protein)
  • Prognosis
    • atrophic gastritis increases risk of gastric cancer 
Presentation
  • Symptoms
    • anemia
      • fatigue
      • dyspnea
    • gastrointestinal
      • glossitis 
    • neurologic
      • cognitive decline
  • Physical examination
    • subacute combined degeneration 
      • lateral corticospinal tracts
        • weakness
        • spasticity
        • hyperreflexia
      • dorsal columns
        • decreased vibration and proprioception sensation
        • gait difficulties
      • spinocerebellar tracts
        • gait difficulties
        • ataxia
        • decreased proprioception sensation
          • impaired proprioception information from the spinal cord to the cerebellum
Labs
  • Serum labs
    • macrocytic and megaloblastic anemia 
    • decreased serum B12 level 
    • reticulocytopenia
    • ↑ serum methylmalonic acid and homocysteine levels
    • anti-intrinsic factor and parietal antibodies 
      • seen in pernicious anemia
  • Peripheral blood and marrow smear show
    • hypersegmented neutrophils and megalocytes 
Differential
  • Folate anemia
    • differentiating factors
      • no neurological manifestations
      • methylmalonic acid levels are not elevated
Treatment
  • Medical
    • intramuscular vitamin B12
      • indication
        • first-line for vitamin B12 deficiency
Complications
  • Irreversible neurological damage if untreated
 

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Questions (8)
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(M2.HE.16.4686) A 63-year-old female complains of weakness, light-headedness, palpitations, and soreness of the tongue. She has a past medical history of Hashimoto’s thyroiditis. Her hematocrit is 29%. On peripheral blood smear, you notice neutrophils with 7 lobes and large oval-shaped red blood cells. On physical exam, you notice the patient has decreased position sense and a loss in vibratory sensation in her lower extremities. Which of the following is most likely present in this patient? Tested Concept

QID: 107396
1

Atrophy of G cells

0%

(0/0)

2

Anti-intrinsic factor antibodies

0%

(0/0)

3

Decreased methylmalonic acid levels

0%

(0/0)

4

Antithrombotic state

0%

(0/0)

5

B12 malabsorption due to Diphyllobothrium latum

0%

(0/0)

M 5 C

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(M2.HE.15.107) A 51-year-old white female presents to her primary care physician for a regular check-up. She endorses eating a healthy diet with a balance of meat and vegetables. She also states that she has a glass of wine each night with dinner. As part of the evaluation, a complete blood count and blood smear were performed and are remarkable for: Hemoglobin 8.7 g/dL, Hematocrit 27%, MCV 111 fL, and a smear showing macrocytes and several hypersegmented neutrophils. Suspecting an autoimmune condition with anti-intrinsic factor antibodies, what other finding might you expect in this patient? Tested Concept

QID: 104747
1

High serum TSH

55%

(12/22)

2

Psorasis

0%

(0/22)

3

Cheilosis

18%

(4/22)

4

Bleeding gums

9%

(2/22)

5

Abdominal colic

14%

(3/22)

M 6 C

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(M2.HE.13.32) A 29-year-old woman presents to her primary care physician with worsening fatigue and lightheadedness over the past several months. She states that she has felt easily fatigued and has experienced several falls during this time frame as well. She drinks 5 to 8 drinks per day and works as a waitress. Her temperature is 98.2°F (36.8°C), blood pressure is 114/64 mmHg, pulse is 98/min, respirations are 12/min, and oxygen saturation is 98% on room air. Laboratory studies are ordered as seen below.

Hemoglobin: 9.0 g/dL
Hematocrit: 29%
Leukocyte count: 6,700/mm^3 with normal differential
Platelet count: 199,400/mm^3
Methylymalonic acid: 1.0 umol/L (normal < 0.40 umol/L)

Which of the following is the most likely etiology of this patient's symptoms?

Tested Concept

QID: 104357
1

Alcohol use

0%

(0/52)

2

Folate deficiency

79%

(41/52)

3

Hypothyroidism

0%

(0/52)

4

Iron deficiency

8%

(4/52)

5

Vitamin B12 deficiency

12%

(6/52)

M 6 E

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