HIGH YIELD NOTES

HEPACIDIN
NEET PG | USMLE | FMGE

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NEET PG | USMLE | FMGE: Hepacidin

NEET PG 2020
Hepcidin inhibits ?
a) Absorption of cobalamine
b) Transfer of iron into enterocytes
c) Folic acid synthesis
d) Respiratory oxidase

Answer: b) Transfer of iron into enterocytes

Hepacidin is an acute-phase reactant and hormone

produced by the liver.
Hepcidin production increases when iron levels rise
above the normal range of 65 to 175 mcg/dL in males
and 50 to 170 mcg/dL in females.
Hepcidin binds to ferroportin, an iron export
transmembrane protein in the macrophages and the
enterocytes. Then it causes the cell to target the
hepcidin-ferroportin complex for lysosomal
degradation. The degradation of ferroportin blocks
iron absorption from enterocytes and iron
mobilization from the macrophages.
It reduces dietary iron absorption and inhibits iron
release from cellular storage - Decreases serum iron.
Iron remains in its intracellular storage form bound to
ferritin when hepcidin levels elevate.
The decreased serum iron levels prevent the invading
pathogen from using the host’s iron stores to grow.

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NEET PG | USMLE | FMGE: Hepacidin

A 42-year-old woman presents with fatigue and a rash

over her nose and cheeks that worsens with sun exposure
and gradually worsening joint pain over the last few
months. Her complete blood count shows a normocytic
normochromic anemia. Which of the following most
likely represents the results of this patient’s iron panel?
a) Low serum iron, low transferrin, high ferritin
b) High serum iron, low transferrin, high ferritin
c) Low serum iron, high transferrin, low ferritin
d) Low serum iron, low transferrin, low ferritin

Answer: a) Low serum iron, low transferrin, high ferritin

Systemic lupus erythematosus (SLE) is an autoimmune

condition caused by a type III hypersensitivity reaction.
Classic symptoms include arthritis and a rash over the
cheeks.
SLE is an autoimmune inflammatory condition and
would lead to an increase in IL-6 production.
IL-6 increases hepcidin gene expression.
Hepcidin decreases serum iron levels by degrading the
transmembrane protein ferroportin. Ferritin levels will
increase because iron is now sequestered intracellularly.
Transferrin levels decrease because less iron is found in
circulation.

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NEET PG | USMLE | FMGE: Hepacidin

A 50-year-old man with diabetes mellitus presents with

hepatomegaly and bronze skin. He does not spend much
time in the sun or tanning beds. Which of the following
most likely explains this patient’s condition?
a) Deposition of copper in bodily tissue
b) Deficient production of a globin chain
c) Increased IL-6 production
d) Mutation in the HFE gene

Answer: d) Mutation in the HFE gene

The classic triad of symptoms in hereditary

hemochromatosis is skin hyperpigmentation, diabetes
mellitus, and liver cirrhosis.
Hereditary hemochromatosis is an autosomal recessive
condition caused by a mutation in the HFE gene that
codes for hepcidin.
An HFE gene mutation decreases hepcidin production.
Serum iron levels will slowly rise because the body can
no longer decrease iron absorption from duodenal
enterocytes or prevent the iron release from
reticuloendothelial macrophages.
Elevated serum iron levels will eventually lead to iron
deposition in bodily tissue. Iron deposition in the liver,
pancreas, and skin accounts for the classic triad of
symptoms seen in hereditary hemochromatosis.

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NEET PG | USMLE | FMGE: Hepacidin

Inflammation/ Infection

Macrophage

IL-6

Liver Mutation HFE

Haemochromatosis
(HFE gene)
(low hepacidin - high
serum iron - deposit in
liver, pancreas, skin)
Hepacidin

Duodenum Spleen | Liver | Bone marrow

Inhibits iron Decrease Ferroportin
absorption Inhibits iron release from macrophage
Iron remains stored as Ferritin
(Increase Ferritin)

Decrease Serum Iron

Decrease Serum Transferrin
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