Case Presentation RK

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Case Presentation - RK
60 year old WM transferred to BH for evaluation
of fevers and night sweats of 1 year duration.
One month PTA he developed weakness and fatigue.
Admitted to OSH where anemia diagnosed. PH-
Long standing arthritis No weight Loss No
meds. PE- Negative except for some proximal
muscle weakness
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Lab- WBC- 9900 Platelets -719,000 Hgb- 9.0
Hct- 26.8 MCV-75 Serum Fe- 12 Retics -
0.8 TIBC- 214 Folate, B12 - N Sat-
6 Haptoglobin- 413 Ferritin - 181, 281 ESR -
122
BM- Non-diagnostic
Impression - 1. Anemia of Chronic Disease 2.
Underlying cause unknown
Followup- CT showed retroperitoneal nodes not
typical of Lymphoma. Exploratory Lap and biopsy
in Feb02 showed Reperitoneal fibrous
histiocytoma.
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Conditions Associated with A.C.D.

• Chonic Infections
• Chronic non-infectious inflammations- RA etc
• Malignant diseases
• Miscellaneous causes

Labs- Anemia - a) N/C N/C but 20-40 have MCV
lt80. b) Serum Iron ?, IBC ?, Sat N/ ? c)
Serum Ferritin ? d) BM- Macrophage Fe ?
Cause of Anemia- Impaired RBC production and
decreased RBC survival. Cytokines (TNF, IL-1 and
Ifs) and disturbed Fe metabolism have been
proposed to have etiologic roles.
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How is info on Fe stores relayed to gut to
regulate Fe absorption ?
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Iron Balance
ACD
HH
Circulating Fe
RE stores
Fe Absorption
Both disorders affect communication between sites
of Fe storage (Hepatocytes and RE system) and
uptake (duodenum). Common factor is Hepcidin
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Lack of hepcidin gene expression and severe
tissue iron overload in upstream stimulatory
factor 2 (USF2) knockout mice. Nicolas G,
Bennoun M, Devaux I, Beaumont C, Grandchamp B,
Kahn A, Vaulont S. Institut National de la Sante
et de la Recherche Medicale 129, Departement
Genetique Developpement et Pathologie
Moleculaire, Institut Cochin de Genetique
Moleculaire, Faculte de Medecine Cochin-Port
Royal, 75014 Paris, France. Proc Natl Acad Sci U
S A 2001 Jul 1798(15)8780-5
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Iron accumulation in liver and pancreas of Usf2/
mice. Liver and pancreas were fixed in
formaldehyde and stained with the Perls' stain
for iron. Nonheme iron stains blue. Liver
sections are from an 8-month-old wild-type mice
(?50) (A), an 8-month-old Usf2/ littermate (B),
and a 19-month-old Usf2/ mouse (?10) (C).
Pancreas section in D is from an 8-month-old
Usf2/ mouse (?12.5). Arrowheads in C indicate
iron in the nucleus of the hepatocyte. Arrowheads
in D point to islets of Langerhans scattered
throughout the exocrine tissue. (E and F)
Age-dependent hepatic and pancreatic nonheme iron
concentration (micrograms of iron per gram dry
tissue) as measured in control (wild-type and
heterozygote mice, ) and Usf2/ mice ().
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Expression of HFE and TfR2 is not modified by
USF2 K/O
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Hepcidin - A Hepatic Antimicrobial Peptide (83AA)
known to be overexpressed during iron
overload.
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Model for hepcidin as a key regulator of Fe
homeostasis
Prediction- Increased Hepcidin induces Fe
deficient state
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Proc. Natl. Acad. Sci. USA, Vol. 99, Issue 7,
4596-4601, April 2, 2002 Severe iron deficiency
anemia in transgenic mice expressing liver
hepcidin Gaël Nicolas, Myriam Bennoun,
Arlette Porteu, Sandrine Mativet, Carole
Beaumont, Bernard Grandchamp, Mario Sirito,
Michèle Sawadogo, Axel Kahn, and Sophie
Vaulont, Département de génétique,
développement et Pathologie Moléculaire, Institut
Cochin, Institut National de la Santé et de la
Recherche Médicale, Centre National de la
Recherche Scientifique, et Université
René Descartes, Faculté de Médecine Cochin-Port
Royal, 75014 Paris, France Institut National de
la Santé et de la Recherche Médicale 409, Faculté
de Médecine Xavier Bichat, 75018 Paris, France
and Department of Molecular Genetics, University
of Texas, M. D. Anderson Cancer Center, Houston,
TX 77030
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Usf2 K/O by another technique does not cause Fe
overload.
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J. Biol. Chem., Vol. 276, Issue 11, 7811-7819,
March 16, 2001 A New Mouse Liver-specific Gene,
Encoding a Protein Homologous to Human
Antimicrobial Peptide Hepcidin, Is Overexpressed
during Iron Overload Christelle Pigeon,
Gennady Ilyin, Brice Courselaud, Patricia
Leroyer, Bruno Turlin, Pierre Brissot, and
Olivier Loréal From the INSERM U522, CHRU
Pontchaillou, Rennes, Laboratoire
d'Anatomo-Pathologie B, CHRU Pontchaillou,
Rennes, and Service des Maladies du Foie, CHRU
Pontchaillou, 35033 Rennes, France
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Fleming and Sly