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USMLE Step 1Haematology and oncologyEP 02 of 14

Hepcidin: why iron falls in inflammation

Hepcidin is the liver hormone that locks iron inside cells. It explains why serum iron drops in inflammation without any bleeding, and how ferritin and iron-binding capacity tell it apart from iron deficiency.

  • 5:34 video
  • 3 min read
  • 12 sources
  • Published 15 Nov 2026
Video lesson · 5:34 · Watch on YouTubeSeries: Hematology: Anemia, Coagulation & Oncology Basics · @medservatory
Chapters (13)
By the end of this lesson

Use hepcidin to explain the iron-study pattern of anaemia of inflammation, and contrast it with iron deficiency.

The short version

  1. Hepcidin degrades ferroportin, the one known iron exit, so iron is trapped inside cells and serum iron falls.
  2. Inflammation raises hepcidin through interleukin-6; iron deficiency lowers it.
  3. Anaemia of inflammation: low serum iron, normal or high ferritin, low or normal iron-binding capacity.
  4. Iron deficiency is the mirror image: low ferritin, high iron-binding capacity, low transferrin saturation.
  5. Serum iron is low in both, so ferritin and iron-binding capacity decide.

Where did the iron go? The hepcidin puzzle

Picture a 68-year-old man admitted with pneumonia. He has not bled and he has not changed his diet, yet within a day or two of admission his serum iron has fallen; in infection, plasma iron can fall within hours.[9]

Nothing has been lost from the body. The iron has been moved out of the blood and locked inside cells. The switch that does this is hepcidin, and understanding it explains the whole iron-study pattern of anaemia of inflammation, and why it differs from iron deficiency.

Daily iron flow, transferrin, ferritin and ferroportin

An adult needs about 20–25 mg of iron every day to make red cells. The diet supplies only a small fraction of this. Most comes from macrophages recycling old red cells.[1][2]

  • Ferroportin is the one known door through which iron leaves cells. It sits on duodenal cells, macrophages and liver cells.[2][3]
  • Transferrin carries iron in the blood.[8]
  • Ferritin is how the body stores iron.[8]

Hepcidin: the master switch that closes ferroportin

Hepcidin is a small hormone made by the liver, and it is the main systemic regulator of iron.[2][4] It binds ferroportin and pulls it into the cell, where it is destroyed.[2][3][4]

With the door gone, iron cannot leave. Macrophages keep the iron from old red cells, the gut cannot pass dietary iron into the blood, and serum iron falls.[2][4][6]

Anaemia of inflammation: interleukin-6 and the iron studies

Interleukin-6, released by immune cells during infection or inflammatory disease such as rheumatoid arthritis, tells the liver to make more hepcidin. So in anaemia of inflammation hepcidin is high and iron is trapped in macrophages.[1][2][6]

  • Serum iron is low, because iron cannot leave the cells that hold it.[6]
  • Ferritin is normal or high. Iron is still held inside macrophages, and ferritin is also an acute-phase reactant.[5][6][7]
  • Iron-binding capacity is low or normal. The liver makes less transferrin, a negative acute-phase reactant, and transferrin saturation is often low.[1][6][7]

Two more hits add to the anaemia: inflammation blunts erythropoietin and shortens red cell survival. The anaemia is usually mild to moderate (haemoglobin usually above 8 g/dL), normocytic at first, and may turn microcytic with time.[2][6]

Iron deficiency vs anaemia of inflammation: the mirror image

In iron deficiency hepcidin is low and ferroportin is wide open, but every store has been emptied.[1][7] One hormone therefore explains both patterns: low hepcidin in iron deficiency, high hepcidin in inflammation.[1][2]

Hepcidin and the iron studies in the two conditions
FindingAnaemia of inflammationIron deficiency
HepcidinHighLow
Serum ironLowLow
FerritinNormal or highLow
Iron-binding capacityLow or normalHigh
Transferrin saturationOften lowLow

Worked example: two patients with low serum iron

Both patients below have a low serum iron, so iron alone cannot decide. Ferritin and iron-binding capacity can.

Patient X and patient Y
  1. Patient X: serum iron 30 µg/dL, iron-binding capacity 520 µg/dL, ferritin 8 ng/mL. Transferrin saturation = 30 / 520 ≈ 5.8%.
  2. X: high binding capacity and a tiny ferritin → iron deficiency.
  3. Patient Y: serum iron 26 µg/dL, iron-binding capacity 190 µg/dL, ferritin 360 ng/mL. Transferrin saturation = 26 / 190 ≈ 13.7%.
  4. Y: low binding capacity and a high ferritin → anaemia of inflammation.

These values are synthetic teaching numbers. Typical adult reference values are serum iron 75–150 µg/dL in men and 60–140 µg/dL in women, iron-binding capacity 250–450 µg/dL and ferritin 30–300 ng/mL, and they vary by laboratory.[7]

Ferritin cut-off when both conditions coexist

If inflammation and iron deficiency are both present, the usual ferritin cut-off of 30 ng/mL no longer applies. In an inflamed patient, a ferritin under about 100 ng/mL still suggests iron deficiency.[6][7]

Treat 100 as a rule of thumb for inflammatory disease rather than a fixed line: cut-offs vary by disease and guideline.[1][6][7]

Practice question

Original · USMLE style
Your turnQB-MS-S1-HEME-002-01

A 61-year-old woman with rheumatoid arthritis has had fatigue for several months. Haemoglobin is 10.2 g/dL and the mean corpuscular volume (MCV) is 84 fL. Serum iron is 44 micrograms/dL, total iron-binding capacity is 235 micrograms/dL and serum ferritin is 270 ng/mL. C-reactive protein is raised.

Which of the following best explains the pattern of her iron studies?
Pick one option. Your answers stay on this device.

Common questions

What does hepcidin do?

Hepcidin is a small hormone made by the liver. It binds ferroportin, the one known iron exit, and pulls it into the cell to be destroyed, so iron cannot leave and serum iron falls.

Why is serum iron low in anaemia of inflammation?

Interleukin-6 makes the liver produce more hepcidin, which degrades ferroportin. Macrophages keep the iron from old red cells and the gut cannot pass dietary iron into the blood, so serum iron falls without any loss of iron from the body.

Why is ferritin high in anaemia of chronic disease?

Iron is still held inside macrophages, so ferritin is normal or high. Ferritin is also an acute-phase reactant, so it rises with inflammation.

How do you tell anaemia of inflammation from iron deficiency?

Serum iron is low in both, so look at ferritin and iron-binding capacity. Low ferritin with a high binding capacity means iron deficiency; a normal or high ferritin with a low or normal binding capacity means inflammation.

What ferritin level suggests iron deficiency in an inflamed patient?

The usual cut-off of 30 ng/mL no longer applies. In an inflamed patient, a ferritin under about 100 ng/mL still suggests iron deficiency, although cut-offs vary by disease and guideline.

Transcript

Read the full narration, by chapter658 words

0:00The case: serum iron falls with no bleeding

A 68-year-old man is admitted with pneumonia. He has not bled and he has not changed his diet, yet within a day or two of admission his serum iron has fallen. Where did the iron go? Today: use hepcidin to explain the iron-study pattern of anaemia of inflammation, and contrast it with iron deficiency.

0:21Daily iron: 20 to 25 mg, mostly recycled

An adult needs 20 to 25 milligrams of iron every day to make red cells. The diet supplies only a small fraction; most comes from macrophages recycling old red cells. Iron leaves cells through one known door,

0:34Ferroportin, transferrin and ferritin

a channel called ferroportin, found on duodenal cells, macrophages and liver cells. In the blood, iron rides on transferrin, and the body stores it as ferritin.

0:48Hepcidin: the master switch

The master switch is hepcidin, a small hormone made by the liver. Hepcidin binds ferroportin and pulls it into the cell to be destroyed. With the door gone, iron cannot leave: macrophages keep the iron from old red cells, the gut cannot pass dietary iron into the blood, and serum iron falls.

1:09Inflammation: interleukin-6 raises hepcidin

Now inflammation. Interleukin six, released by infection or arthritis, tells the liver to make more hepcidin. So in anaemia of inflammation hepcidin is high, and iron is trapped in macrophages. Serum iron is low, but iron is still held

1:25Anaemia of inflammation: the iron studies

inside macrophages, so ferritin is normal or high; ferritin is also an acute-phase reactant. The liver also makes less transferrin, a negative acute-phase reactant, so the total iron-binding capacity is low or normal, and transferrin saturation is often low. Two more hits: inflammation blunts erythropoietin

1:48Two more hits: EPO and red cell survival

and shortens red cell survival. The anaemia is usually mild to moderate, normocytic at first, and may turn microcytic with time. Iron deficiency is the mirror image.

2:01Iron deficiency: the mirror image

Hepcidin is low, ferroportin is wide open, and every store is emptied, so ferritin is low, the iron-binding capacity is high, and saturation is low. Low hepcidin in iron deficiency, high hepcidin in inflammation: one hormone explains the pattern. Compare two patients.

2:23Compare two patients, X and Y

Patient X: serum iron 30 microg/dL, iron-binding capacity 520, ferritin eight. Patient Y: serum iron 26, iron-binding capacity 190, ferritin 360. Both have low serum iron, so iron alone cannot decide. X is iron deficiency: high binding capacity, tiny ferritin. Y is inflammation: low binding capacity, high ferritin. If both coexist,

2:57Ferritin cut-off when both coexist

the usual cut-off of 30 no longer applies: in an inflamed patient, a ferritin under about 100 still suggests iron deficiency.

3:08Practice question

Your turn. A 61-year-old woman with rheumatoid arthritis has had fatigue for several months. Haemoglobin is 10.2 g/dL and MCV is 84 femtolitres. Serum iron is 44 microg/dL, total iron-binding capacity is 235, and ferritin is 270 nanograms per millilitre. C reactive protein is raised. Which of the following best explains the pattern of her iron studies? A, increased ferroportin expression on enterocytes, leading to excess dietary iron absorption. B, depletion of body iron stores from chronic blood loss. C, failure of erythroblast mitochondria to insert iron into protoporphyrin. D, increased hepcidin, leading to ferroportin degradation and iron retention in macrophages. E, defective globin chain synthesis with unbalanced alpha and beta chains. Pause here and decide. A is out: low hepcidin is the iron-deficiency

4:17Answer and explanation

state, with ferroportin wide open, and her stores are not empty. B is out: blood loss gives a low ferritin and a high binding capacity, not a ferritin of 270 and a low binding capacity. C is out: failed iron insertion, as in sideroblastic anaemia, raises serum iron and saturation. E is out: unbalanced globin chains leave the iron studies normal. So the answer is D. Inflammation raises hepcidin, which degrades ferroportin, so iron stays in macrophages: low serum iron, high ferritin, low binding capacity.

5:00Recap and next lesson

Three things to keep. One: hepcidin degrades ferroportin, trapping iron in cells and lowering serum iron. Two: inflammation raises hepcidin through interleukin six; iron deficiency lowers it. Three: low iron with high ferritin and low binding capacity means inflammation; low ferritin with high binding capacity means iron deficiency. Next, macrocytic anaemia: vitamin B12 versus folate.

Sources

Numbers in the text, e.g. [1], point here
  1. Nairz M, et al. Iron regulatory proteins and anaemia of inflammation. 2016. europepmc.org/article/PMC/PMC5065583
  2. Lanser L, et al. Iron metabolism and inflammation. 2021. europepmc.org/article/PMC/PMC8619077
  3. Mansour et al. Ferroportin and iron export. 2025. europepmc.org/article/PMC/PMC12722858
  4. Liu et al. Hepcidin and ferroportin. 2025. europepmc.org/article/PMC/PMC12233014
  5. Barcellini W, et al. Ferritin as an acute phase protein. 2015. europepmc.org/article/PMC/PMC4706896
  6. MSD Manual Professional Version. Anemia of Chronic Disease. msdmanuals.com/professional/hematology-and-oncology/anemias-caused-by-deficient-erythropoiesis/anemia-of-chronic-disease
  7. MSD Manual Professional Version. Iron Deficiency Anemia. msdmanuals.com/professional/hematology-and-oncology/anemias-caused-by-deficient-erythropoiesis/iron-deficiency-anemia
  8. OpenStax Anatomy and Physiology 2e, 18.3 Erythrocytes. openstax.org/books/anatomy-and-physiology-2e/pages/18-3-erythrocytes
  9. Int J Mol Sci 2021, hypoferraemia of inflammation (hook case). europepmc.org/article/PMC/PMC8123811
  10. MSD Manual Professional Version. Sideroblastic Anemias. msdmanuals.com/professional/hematology-and-oncology/anemias-caused-by-deficient-erythropoiesis/sideroblastic-anemias
  11. Lazarte et al. 2015, iron studies in beta-thalassaemia trait versus iron deficiency. europepmc.org/article/PMC/PMC4615862
  12. Patra et al. 2025, beta-thalassaemia trait versus iron deficiency. europepmc.org/article/PMC/PMC12705022

Patients X and Y and the practice question use synthetic values; reference ranges on screen are typical adult values and vary by laboratory.

The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.

Image credits. Illustrations: Servier Medical Art (smart.servier.com), CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), adapted (cropped, recoloured, outlined): lungs, liver, duodenum, red cell, rheumatoid arthritis hand. macrophage icon by Servier (via bioicons.com), CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/), adapted (recoloured, outlined). bone_marrow icon by El-Jayawant (via bioicons.com), CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), adapted (recoloured, outlined). Original diagrams: the serum-iron schematic, iron flow, ferroportin door and hepcidin plug, dials, gauges, mirror page, lab cards, ferritin ruler. No AI-generated teaching images.

Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-HEME-002.

For exam study only, not medical advice. Read the medical disclaimer.

In this series

Playlist on YouTube
← Previous · EP 01Microcytic anaemia: four causes, four iron fingerprints
  1. EP 01Microcytic anaemia: four causes, four iron fingerprints5:37
  2. EP 02Hepcidin: why iron falls in inflammation5:34
  3. EP 03B12 vs folate deficiency: MMA, homocysteine and the nerves5:23
  4. EP 04Intravascular vs extravascular haemolysis: site and labs5:27
  5. EP 05G6PD deficiency vs hereditary spherocytosis, by mechanism5:36
  6. EP 06Sickle cell disease pathophysiology: HbS to vaso-occlusion5:26
  7. EP 07Primary haemostasis: platelet adhesion, activation and aggregation5:53
  8. EP 08Coagulation cascade: PT vs aPTT, pathway by pathway5:21
  9. EP 09Von Willebrand disease vs haemophilia: the labs that separate them5:32
  10. EP 10Anticoagulants: target, monitoring test and reversal agent5:34
  11. EP 11Heparin-induced thrombocytopenia: why a low count clots5:29
  12. EP 12DIC vs TTP vs HUS: mechanism and the PT/PTT5:33
  13. EP 13AML vs ALL vs CML vs CLL: leukemia classification made simple5:44
  14. EP 14Oncogenes vs tumour suppressor genes: one hit or two5:17