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Pernicious Anemia By Naomi Bryner

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1 Pernicious Anemia By Naomi Bryner

2 Liver & onions

3  Vitamin B12  Sources  Functions  Autoimmune mechanism  Anti-intrinsic factor Abs  Anti-parietal cell Abs  Case Study  Expecting cancer  Chronic fatigue Overview

4 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

5 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

6 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

7 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 CD 4 + 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  CD 4 + recognizes H+/P + - ATPase as H. pylori  Suspected genetic causation - FUT2 gene  Makes protein that is distantly involved in H antigen production

8 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

9 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

10 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?

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