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Transcript
ANEMIA & IRON
METABOLISM
Hossein Piri
Department of Biochemistry and Genetics,
School of Medicine,
Qazvin University of Medical Sciences, Qazvin, Iran
September 2014
Classification of anemia

Morphologic
Normocytic: MCV= 80-100fL
 Macrocytic: MCV > 100 fL
 Microcytic : MCV < 80 fL


Pathogenic (underlying mechanism)
Blood loss (bleeding)
 Decreased RBC production
 Increased RBC destruction/pooling

Normocytic Anemias


Acute post-hemorrhagic
anemia
Hemolytic anemia
(except thalassemia and
some other Hb
disorders)
Endocrin diseases
 Renal failure
 Liver disease
 Chronic disease anemia
 Protein malnutrition
 Hypovitaminosis C

Microcytic anemias
Iron deficiency anemia
 Thalassemia
 Sideroblastic anemia



Hereditary

Chronic lead poisoning
Anemia of chronic diseases
(some cases)
Megaloblastic Macrocytic Anemias
Vit B12 deficiency
 Folic acid deficiency
 Other.

Pathogenic classification
(Causes of anemia)

Relative (increased plasma volume)
 Decreased RBC production
 Blood loss


Anemia due to acute bleeding
Increased RBC destruction
Pathogenic classification
(Causes of anemia)

Decreased RBC production
– Decreased Hb production
– Defective DNA synthesis
– Stem cell defects

Blood loss
– Anemia due to acute bleeding


Increased RBC destruction
Relative(increased plasma volume)
Decreased Hb production
Iron deficiency anemia
 Thalassemia
 Sideroblastic anemia
 Lead poisoning

Defective DNA synthesis
Vit B12 deficiency
 Folic acid deficiency
 Other.

Anemias caused by increased
RBC destruction (hemolytic anemias)
Can be classified as;
 Hereditary hemolytic diseases
 Acquired hem. Diseases
Iron
&
(TIBC)
‫آهن‬
‫‪ ‬عملکرد‪:‬‬
‫‪ ‬انتقال اکسیژن‬
‫‪ ‬تنفس‬
‫‪ ‬متابولیسم اسیدهای آمینه و رادیکال آزاد‪ ،‬لیپیدها‪ ،‬فسفریلسیون‬
‫اکسیداتیو‬
‫‪ ‬جزئی از ‪ Hb‬و متالوآنزیم ها‬
‫تركيبات آهن داربدن‬
‫‪ ‬آهن هم(‪)Heme Iron‬‬
‫ترانسفرين‬
‫هموسيدرين‬
‫فريتين‬
‫‪ ‬آهن غيرهم )‪(None heme Iron‬‬
‫هموگلوبين)‪(Hb‬‬
‫ميوگلوبين‬
‫آهن بافتي (آنزيمهاي تنفس ي)‬
Iron Transport
into Plasma
Duodenal
cytochrome b
Senescent
Macrophages
RBC
Macrophage
Hb
Fe
FerroFerroportin
portin 1 1
Ferroportin 1
Adapted frlm Andrews,
NEJM 1999;341:1986
Fe+2+2
Fe
Ceruloplasmin
Fe+3
Tf
Receptor-Mediated Endocytosis
Andrews N, NEJM 1999;341:1986
Food iron is predominantly in the ferric state.
In the stomach, where the pH is less than 4, Fe3+
can dissociate and react with low-molecular weight
compounds such fructose, ascorbic acid, citric acid,
amino acids to form ferric complexes soluble in
neutral pH of intestine fluid.
A protein DMT1 (divalent metal transporter 1),
which transports all kinds of divalent metals, then
transports the iron across the cell membrane of
intestinal cells. These intestinal lining cells can
then store the iron as ferritin.
The transfer of iron from the storage ferritin (as
Fe3+ ) involves reduction to ferrous state – Fe2+ in
order for it to be released from ferritine.
The Fe2+ is subsequently again oxidized by
ferroxidase ceruloplasmin and transported bound to
plasma transferrin to storage sites in the bone
marrow, liver muscle, other tissues.
‫جذب ‪ ،‬انتقال و دفع آهن(متابوليسم آهن)‬
‫اريتروپوئز و سنتز هم‬
‫‪Bone marrow‬‬
‫)‪RBC(blood‬‬
‫خون ريزي و دفع‬
‫از طرق ديگر‬
‫اريتروپوئز غيرموثر‬
‫‪Phagocytes‬‬
‫تخريب ‪RBC , Hb‬‬
‫جذب روده اي‬
‫& ‪Plasma‬‬
‫‪ECF‬‬
‫ذخيره سازي به‬
‫صورت فريتين و‬
‫هموسيدرين‬
Transferrin (TRF)









TRF (sidrophilin) is a plasma transport protein for iron (β1)
Single polypeptide chain ,79.6 kDa, 5.5% carbohydrate.
Reversibly bind to divalent cations,
TRF accounts for TIBC of plasma
One TRF binds two Fe+3, TRF- Fe+3 complex transports iron
to cells
Every cell type has surface receptors of TRF
TRF is synthesized by liver
Plasma levels are regulated by iron availability (iron↓, TRF↑)
One-half of TRF exists in extravascular spaces
5/23/2017
Plasma Proteins
19
Receptors for TRF

After binding the TRF - Fe+3 -receptor complex is
internalized, resulting in release of iron from TRF

Free Fe+3, is cytotoxic, is reduced and incorporated into
ferritin and hemosiderin, for synthesis of compounds,
such as Hb, myoglobin, and cytochromes

The receptor-apo TRF complex is recycled to the cell
surface where the apo TRF is released and recycled,
making the receptor available again for binding
5/23/2017
Plasma Proteins
20
Clinical Significance
Differential diagnosis of anemia:
 In hypochromic microcytic anemia:
Elevated TRF & less saturated : Iron deficiency
(saturation normally 30% to 38%)
 Low or normal TRF & highly saturated: Iron nondependency

Estrogen increases TRF synthesis,

TRF is a negative APP
5/23/2017
Plasma Proteins
21
‫ناهنجاريهاي متابوليسم آهن‬
‫آرتريت‬
‫آريتمي قلبي‬
‫كمبود آهن )‪(Iron deficiency‬‬
‫افزايش آهن )‪(Iron overload‬‬
‫ هموسيدروز‬‫‪ -‬هموكروماتوز(اوليه‪ ،‬ثانويه)‬
‫نارسايي قلبي‬
‫سيروزكبدي‬
‫هيپوتيروئيديسم‬
‫سرطان كبد‬
‫ديابت مليتوس‬
‫هيپرپيگمانتاسيون‬
‫آهن‬
‫‪ ‬اثرات کمبود‪:‬‬
‫‪ ‬آنمی هیپوکرومیک میکروسیت‬
‫‪ ‬التهاب دهانی‬
‫‪ ‬دیستروفی ناخن دست‬
‫‪ ‬اثرات سمیت‪:‬‬
‫‪ ‬هموکروماتوز اولیه‬
‫علل عمده افزايش ‪Fe‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫افزايش تخريب ‪ RBC‬يا هموليز‬
‫افزايش رها سازي آهن و يا فريتين ازبافتها (نكروزحاد كبد)‬
‫كاهش توليد ‪( Hb‬مسموميت با ‪ ، pb‬كمبود پيريدوكسين)‬
‫اريتروپوئز غير موثر)‪(Ineffective erythropoesis‬‬
‫افزايش جذب آهن)‪(Iron overload‬‬
‫مصرف قرصهاي آهن‬
‫ترانسفوزيون مكرر‬
‫مصرف داروهاي ضد حاملگي پروژستروني‬
‫آلودگي سرنگ يا ظرف نمونه‬
‫علل عمده كاهش ‪Fe‬‬
‫‪ ‬سندرم سوءتغذيه و سوءجذب‬
‫‪ ‬خونريزي مزمن و مكرر‬
‫‪ ‬اختالل دررهاسازي آهن ازسيستم رتيكولواندوتليال(عفونت و اختالالت التهابي مزمن)‬
‫‪ ‬بيماريهاي مزمن(عفونت و بدخيمي)‬
‫‪ ‬بيماريهاي حاد(عفونت)‬
‫‪ ‬كواشيوركور‬
‫‪ ‬نفروز(سندرم نفروتيك)‬
Porphyrines
Heme Biosynthesis
‫نقش ویتامين های ‪B9‬و‬
‫‪ B12‬دراریتروپوئز‬
‫بيوسنتزپورين ها ازمسيرتوليد داخلي‬
CO2
Gly
Asp
MethenylTHF
FormylTHF
Amide Nitrogen of
Gln
dTMP‫سنتز‬
suicide inhibitor
Breast and
colon cancer
‫تیمیدیلت سنتاز‬
Aminopterin
Trimethoprim
Essential Nutrients for Erythropoiesis
Folic Acid
Enzyme
Function
Thymidylate
synthetase
DNA synth.
Cobalamin
Methionine
synthetase
DNA synth.
Iron
Ferrochelatase
Hb synth.
Source
Vegetables,
fruit, liver
Meats, milk,
eggs
Meats,
fortification
Absorp.
Prox. Intest.
Term. Ileum
Prox. Intest.
Storage
Liver
Liver, kidney
Macrophages