Transcript Pernicious Anemia - York College of Pennsylvania

https://www.youtube.com/watch?v=6OUaYcknxLU
Pernicious Anemia
By Naomi Bryner
Liver
& onions
Overview
 Vitamin B12
 Sources
 Functions
 Autoimmune mechanism
 Anti-intrinsic factor Abs
 Anti-parietal cell Abs
 Case Study
 Expecting cancer
 Chronic fatigue
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
 Methionine synthase
 No de novo pathway
 Coupled methylation
 Methylmalonyl CoA
Mutase
 Generates radicals
 Produces Succinyl-CoA
 Free folate
 Hematopoiesis
 Nucleic acids
(Andres, et al.; Song, et al.)
Autoimmune mechanism
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
(Moretti, et al.; Antico, et al.)
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 αand 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.)
Patient with chronic
fatigue (Kadikoylu, et al.)
 Male age 75 at high risk of
prostate cancer
 Female age 55 examined
after several months fatigue
 Active vitamin B12 (IF
bound) was depleted before
all vitamin B12
 Detection of multiple factors
led to PA diagnosis
 Further testing led to the
 Lack of IF bound vitamin B12
diagnosis of a type 1 gastric
can affect DNA synthesis
carcinoid tumor
 Overall expectation: Increase
mutation rate
 Not generally detected alone
 In this case: Retardation of
cancer growth possibly due
to poor DNA synthesis
 Annual follow-up
examinations
 Fruitless biopsy
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?