Pernicious AnemiaBy Naomi Bryner

https://www.youtube.com/watch?v=6OUaYcknxLU

Liver

& onions

Vitamin B12 Sources

Functions

Autoimmune mechanism Anti-intrinsic factor Abs

Anti-parietal cell Abs

Case Study Expecting cancer

Chronic fatigue

Overview

chemistry.about.com

Vitamin B12 – Sources

Dietary sources Meat, poultry, shellfish,

eggs, diary

Use about 1 μg/day

Liver storage Lasts months-decades

Requires Intrinsic Factor Secreted by gastric

parietal cells

Vitamin B12 – Functions (Andres, et al.; Song, et al.)

Methionine synthase No de novo pathway

Coupled methylation

Methylmalonyl CoA Mutase Generates radicals

Produces Succinyl-CoA

Free folate Hematopoiesis

Nucleic acids

Autoimmune mechanism (Moretti, et al.; Antico, et al.)

Anti-intrinsic factor antibodies

Intrinsic factor blocking abs Type I

Works competitively

Fills binding sites

Intrinsic factor binding abs Type II

Binds with vitamin B12

Causes precipitation

Autoimmune mechanism (Banka, et al.; Torbenson, et al.)

Anti-parietal cell antibodies

Created during type A gastric infection

Dendritic cells present H+/P+-ATPase as Ag

Th1 CD4+ T cells attack α-

and β-subunits of

H+/P+-ATPase Proton pump (H+ out, K+ in)

Constitute most coating of parietal cells

Preexisting due to prior helicobacter pylori infection Affects >50% world pop.

Only 20% show symptoms

CD4+ recognizes H+/P+-

ATPase as H. pylori

Suspected genetic causation - FUT2 gene Makes protein that is

distantly involved in H antigen production

Case Studies

Patient expecting cancer (Tisman, et al.)

Male age 75 at high risk of prostate cancer

Active vitamin B12 (IF bound) was depleted before all vitamin B12

Lack of IF bound vitamin B12 can affect DNA synthesis Overall expectation: Increase

mutation rate

In this case: Retardation of cancer growth possibly due to poor DNA synthesis

Patient with chronic fatigue (Kadikoylu, et al.)

Female age 55 examined after several months fatigue

Detection of multiple factors led to PA diagnosis

Further testing led to the diagnosis of a type 1 gastric carcinoid tumor Not generally detected alone

Fruitless biopsy

Annual follow-up examinations

Pernicious Anemia

Malabsorption of vitamin B12 due to lack of parietal cells or intrinsic factor Intrinsic factor – blocking (competition), binding (precipitation)

Parietal cells - H+/K+-ATPase ‘confused’ for helicobacter pylori

Active vitamin B12 works with methionine synthase, methylmalonyl-CoA mutase, and folate Synthase – methylation of essential amino acid

Mutase – uses radicals to make succinyl Co-A (citric acid cycle)

Folate – aids maturation of erythrocytes, methylates nucleic acids

The exact causes of the autoimmune responses related to PA are unknown Cancers (especially stomach), age-related gastric atrophy,

genetics

Literature Cited

Andres, E., Serraj, K. 2012. Optical management of pernicious anemia. Dove Medical Press [serial online] 3: 97-103.

Antico, A., Tampoia, M., Villalta, D., Tonutti, E., Tozzoli, R., and Bizzaro, N. 2012. Clinical usefulness of the serological gastric biopsy for the diagnosis of chronic autoimmune gastritis. Clinical and Developmental Immunology [serial online] ePub.

Banka, S., Ryan, K., Thomson, W., and Newman, W.G. 2011. Pernicious anemia – Genetic insights. Autoimmunity Reviews [serial online] 10(8): 455-459.

Kadikoylu, G., Yavasoglu, I., Yukselen, V., Ozkara, E., and Bolamin, Z. 2006. Treatment of solitary gastric carcinoid tumor by endoscopic polypectomy in a patient with pernicious anemia. World Journal of Gastroenterology [serial online] 12(26): 4267-4269.

Moretti, R.,Torre, P., Antonello, R.M., Cattaruzza, T., Cazzato, G., Bava, A. 2004. Vitamin B12 and folate depletion in cognition: A review. Neurology India [serial online] 52(3): 310-318.

Song, I.C., Lee, H.J., Kim, H.J., Bae, S.B., Lee, K.T., Yang, Y.J., Park, S.Y., Cho, D.Y., Kim, N.Y., Cho, I.S., and Jo, D.Y. 2013. A multicenter retrospective analysis of the clinical features of pernicious anemia in a Korean population. Journal of Korean Medical Science [serial online] 28(2): 200-204.

Tisman, G.,Kutik, S., Rainville, C. 2009. Coexistence of pernicious anemia and prostate cancer –‘an experiment of nature’ involving vitamin B12 modulation of prostate cancer growth and metabolism: a case report. Journal of Medical Case Reports [serial online] 3: 9295.

Torbenson, M., Abraham, S.C., Boitnott, J., Yardley, J.H., and Wu, T.T. 2002. Autoimmune gastritis: Distinct histological and immunochemical findings before complete loss of oxyntic glands. Modern Pathology [serial online] 15(2): 102-109.

Questions?