Prof 2, Chapter 5 Iron

Total body iron in males

About 4 grams.

Total body iron in females

About 2–3 grams.

Iron as trace element

Iron is the most abundant trace element in humans.

Main location of body iron

Most body iron is located in red blood cells as hemoglobin.

Iron in hemoglobin

About 65–70% of total body iron.

Iron in myoglobin

About 3–5% of total body iron.

Iron in enzymes

About 1% of total body iron.

Iron stored in liver, spleen, and bone marrow

About 20–30% of total body iron.

Main storage forms of iron

Ferritin and hemosiderin.

Important molecules in iron metabolism

DMT1, ferroportin, hepcidin, transferrin, ferritin, hemosiderin.

DMT1 function

Transports Fe2+ across enterocytes in the duodenum.

Ferroportin function

Exports iron from enterocytes and macrophages into plasma.

Hepcidin function

Main regulator of iron metabolism; inhibits ferroportin.

Hemoglobin iron

Main fraction of body iron, located in erythrocytes.

Stored iron

Iron stored as ferritin and hemosiderin in liver, spleen, and bone marrow.

Tissue iron

Iron present in enzymes such as cytochromes, catalase, and peroxidase.

Labile iron pool

Readily available, exchangeable pool of iron.

Transport iron

Iron bound to transferrin in plasma.

Amount of transport iron

Only about 0.1% of total body iron.

Why does iron not circulate freely?

Free iron is toxic.

Main plasma carrier of iron

Transferrin.

Apotransferrin

Transferrin protein without iron.

Transferrin

Apotransferrin after binding Fe3+.

How many Fe3+ ions can transferrin bind?

Two Fe3+ ions per molecule.

Main role of transferrin

Transports iron safely in blood to tissues.

How does transferrin deliver iron to cells?

Via transferrin receptors.

Important transferrin target tissue

Bone marrow, for hemoglobin synthesis.

What happens to iron inside cells?

It is used, stored as ferritin/hemosiderin, or exported.

Daily dietary iron intake

About 10–20 mg per day.

Role of stomach acid in iron absorption

HCl reduces Fe3+ to Fe2+.

Absorbable form of iron

Fe2+.

Main site of iron absorption

Duodenum.

Percentage of ingested iron absorbed

About 10–15%.

Fate of unabsorbed iron

Excreted in feces.

Other iron losses

Urine, skin, and intestinal mucosa.

Apoferritin function

Binds Fe2+ and stores it as ferritin.

Ferritin

Main soluble iron storage protein.

Hemosiderin

Insoluble storage form of iron.

Low iron and hepcidin

Low iron leads to low hepcidin.

Low iron and ferroportin

Ferroportin remains active, so more iron enters circulation.

Result of low iron regulation

Iron absorption is promoted.

High iron and hepcidin

High iron leads to increased hepcidin release from the liver.

High iron and ferroportin

Hepcidin binds ferroportin and causes its degradation.

Result of high iron regulation

Iron absorption is reduced or prevented.

Main rule of iron regulation

Low iron → low hepcidin → more absorption; high iron → high hepcidin → less absorption.

Fate of intracellular iron

Instant use, storage, or export.

Instant use of intracellular iron

Iron is transported directly to where it is needed.

Storage of intracellular iron

Iron is stored as ferritin.

Export of intracellular iron

Iron is exported through ferroportin.

Ceruloplasmin role

Oxidizes Fe2+ to Fe3+ so iron can bind transferrin.

Cells with highest iron export

Macrophages, hepatocytes, and enterocytes.

Macrophage role in iron metabolism

Recycle iron from old red blood cells.

Hepatocyte role in iron metabolism

Store iron and release it when needed.

Enterocyte role in iron metabolism

Regulate dietary iron absorption and release into blood.

Groups most at risk of iron deficiency

Children, young women, and elderly people.

Bone marrow test for iron deficiency

Prussian blue staining for iron.

Serum iron determination

Measures circulating iron.

Serum transferrin

Main transport protein measured in iron status evaluation.

TIBC

Total iron binding capacity.

UIBC

Unsaturated iron binding capacity.

Transferrin saturation

Percentage of transferrin binding sites occupied by iron.

Serum ferritin

Reflects body iron stores.

Ferritin in iron deficiency

Low.

Erythrocyte protoporphyrin in iron deficiency

Increased.

Soluble transferrin receptor in iron deficiency

Elevated.

Reticulocyte hemoglobin

Shows recent iron supply to red blood cell precursors.

Hemosiderosis

Iron overload without tissue damage.

Causes of hemosiderosis

Excess iron supplements or multiple blood transfusions.

Hemochromatosis

Iron overload with tissue damage.

Main organs damaged in hemochromatosis

Liver, pancreas, heart, skin, and endocrine glands.

Classic symptoms of hemochromatosis

Bronze skin pigmentation, cirrhosis, and diabetes mellitus.

Other symptoms of hemochromatosis

Cardiomyopathy, endocrine disorders, and joint disease.

Primary hemochromatosis

Genetic disorder causing increased intestinal iron absorption.

Secondary hemochromatosis

Iron overload caused by external factors.

Causes of secondary hemochromatosis

Frequent blood transfusions, excess iron therapy, or accidental ingestion of large iron doses.

Hemosiderin appearance

Golden-brown granular pigment.

Hemosiderin origin

Byproduct of hemolysis.

Hemosiderin storage form

Insoluble storage form of iron.

Where is hemosiderin detected?

Inside cells, especially macrophages.

Normal serum iron in adult men

14.0–27.0 µmol/L.

Normal serum iron in adult women

12.5–25.0 µmol/L.

Normal serum iron in newborns

25.0–34.0 µmol/L.

Causes of low serum iron

Malnutrition, malabsorption, severe bleeding, infections, autoimmune diseases, and carcinomas.

Why can infections lower serum iron?

Iron is sequestered in macrophages.

Why can carcinomas lower serum iron?

Iron is trapped in the reticuloendothelial system and becomes unavailable.

Causes of increased serum iron

Iron overload, decreased erythropoiesis, hepatitis, cirrhosis, and oral contraceptives.

Decreased erythropoiesis causes of increased serum iron

Lead poisoning and deficiencies of vitamin B12, B6, or folic acid.

Why can hepatitis and cirrhosis increase serum iron?

Stored iron is released from damaged liver tissue.

Serum iron measurement type

Colorimetric test.

Serum iron test principle

Iron is released from transferrin, reduced, and forms a colored complex.

First step in serum iron determination

Fe3+ is released from transferrin by acid treatment.

Reduction step in serum iron determination

Fe3+ is reduced to Fe2+.

Chromogen in serum iron determination

Ferrozine.

Color of serum iron complex

Purple or pink.

Serum iron spectrophotometry principle

Color intensity is proportional to serum iron concentration.

Why is serum iron alone unreliable?

It varies strongly with diet, hemolysis, and circadian rhythm.

Serum iron daily variation

Usually higher in the morning.

Factors affecting serum iron

Diet, iron supplements, acute infection, menstrual cycle, and circadian rhythm.

Possible daily serum iron fluctuation

Up to about 70% between morning and night.

TIBC meaning

Total capacity of transferrin to bind iron.