Professional Documents
Culture Documents
• Biochemistry
• Recent advances in understanding of iron
metabolism
• Role in disease
Iron
• Element (Fe)
• Molecular weight 56
• Abundance
• May be 2+ or 3+
– Ferrous (2+) “reduced” - gained an electron
Fe+++ + e- Fe++
Iron Biochemistry
Fe2+ ↔ Fe3+ + e-
• An essential element
Iron Toxicity
• Iron can damage tissues
• Catalyzes the conversion of hydrogen peroxide to
free-radical ions
• Free-radicals can attack:
– cellular membranes
– Proteins
– DNA
• Thus it must be bound/ carried by various
proteins
• Iron excess possibly related to cancers, cardiac
toxicity and other factors
Principle
• Crypt Hypothesis
• Hepcidin
Duodenal Iron Absorption –
‘The Crypt Hypothesis’
• Precursor cells
proliferate in the crypt.
• As they mature and
differentiate, they
migrate up the villus.
• Their apical membrane
develops microvilli and
absorptive transport
enzymes.
The ‘Crypt Hypothesis’
Hematology 2006;2006:505-516
x
x
x
IRON FLOWS ARE REGULATED BY THE
HEPCIDIN/FERROPORTIN INTERACTION
x
x
x Plasma
Fe
Hepcidin
ANEMIA
INFLAMMATION HYPOXIA
IRON
hepcidin
Hepcidin regulation by anaemia
IRON SIGNAL
ERYHTROPOIETIC SIGNAL
SUMMARY
IRON OVERLOAD
Transferrin Iron
Differential diagnosis of hypochromic anaemia.
Principle
• In homeostasis - intake of any element equals
loss of any element
– nitrogen, water, salt, iron
Shift to left
Blood & Bone Marrow
• BLOOD Film:
– Microcytosis, Hypochromia, Anulocytes, Anisocytosis,
Poikilocytosis
• BONE MARROW Film:
– High cellularity.
– Mild to moderate erythroid hyperplasia (25-35%; N: 16 –
18%)
– Cytoplasm of polychromatic and pyknotic normoblasts
is scanty (indicating its immaturity), vacuolated and
irregular in outline. This type of erythropoiesis has been
described as micronormoblastic (micronormoblastic
erythropoiesis)
– Staining the BM aspirates for iron (hemosiderin) gives
indicate that normoblast iron are absent. i.e. Absence of
hemosiderin stainable iron. Usually BM iron is scored
from 0 to +4 (0, +1, +2, +3, +4), in IDA it is 0.
IDA blood film:
Anisocytosis, Hypochromia, Microcytosis.
IDA Anulocyte
BM in IDA show erythroid hyperplasia, but
unfortunately ineffective
Prussian Blue Stain for iron of BM
30%
TIBC
Saturation
Iron Deficiency
10%
TIBC
Hemochromatosis (iron overload)
Saturation
60-75%
TIBC
NR transferrin levels take up 250-430 µg/dL in the lab
Transferrin vs iron binding capacity
• Normal Transferrin level= 240-430 mg/dL
• Total Iron binding capacity (TIBC): amount of
iron (as a reagent, excess iron is added by you
in the lab) that can be taken up by washed
transferrin molecules in patient serum in the
laboratory, in µg/dL, normal = 253-435 µg
iron/dL
• Serum iron (Fe)= 75-175 µg/dL
• Transferrin saturation (TfS)= [Fe/TIBCx100]
(%), normal 20-50%, with a mean value of 30%.
Transferrin and TIBC
• NR 15-300 µg/L
Serum Ferritin
TIBC
HIGH N or ↓
- BM Fe
+