2. Chapter 5. iron
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108 Terms
What is iron?
The most abundant trace element in humans.
Total body iron in adult males
About 4 grams.
Total body iron in adult females
About 2–3 grams.
Where is most body iron found?
In hemoglobin inside red blood cells.
How much iron is found in hemoglobin?
About 65–70%.
How much iron is found in myoglobin?
About 3–5%.
How much iron is found in enzymes?
About 1%.
Which enzymes contain iron?
Cytochromes, catalase, and peroxidase.
How much iron is stored in the body?
About 20–30%.
Where is iron stored?
Liver, spleen, and bone marrow.
In which forms is iron stored?
Ferritin and hemosiderin.
What is hemoglobin iron?
Iron located in erythrocytes and used for oxygen transport.
What is tissue iron?
Iron present in enzymes and functional proteins.
What is transport iron?
Iron bound to transferrin in plasma.
How much of total body iron is transport iron?
Only about 0.1%.
Why is transport iron important?
It delivers iron safely to tissues.
Why does iron not circulate freely?
Free iron is toxic.
What is transferrin?
The main plasma protein that transports iron.
What is apotransferrin?
Transferrin without iron.
What happens when apotransferrin binds iron?
It becomes transferrin.
Which iron form binds to transferrin?
Fe³⁺.
How many Fe³⁺ ions can one transferrin molecule bind?
Two.
Main role of transferrin
Transport iron safely in blood and deliver it to tissues.
Which tissue especially needs transferrin-delivered iron?
Bone marrow for hemoglobin synthesis.
What is DMT1?
Divalent metal transporter 1 that transports Fe²⁺ into enterocytes.
Where does DMT1 absorb iron?
Mainly in the duodenum.
What is ferroportin?
Protein that exports iron from enterocytes and macrophages into plasma.
What is hepcidin?
Main regulator of iron metabolism.
What does hepcidin inhibit?
Ferroportin.
What happens when hepcidin is high?
Ferroportin is blocked, so iron absorption and release decrease.
What happens when hepcidin is low?
Ferroportin stays active, so iron absorption and release increase.
Low iron regulation
Low hepcidin, active ferroportin, increased iron absorption.
High iron regulation
High hepcidin, inhibited ferroportin, decreased iron absorption.
Daily dietary iron intake
About 10–20 mg/day.
Where is iron mainly absorbed?
Duodenum.
Which iron form is better absorbed?
Fe²⁺.
What does stomach HCl do to iron?
Helps reduce Fe³⁺ to Fe²⁺.
How much dietary iron is absorbed?
About 10–15%.
What happens to unabsorbed iron?
It is mainly excreted in feces.
What is ferritin?
The main soluble storage protein for iron.
What is apoferritin?
The protein shell of ferritin without stored iron.
What is hemosiderin?
An insoluble storage form of iron.
Ferritin vs hemosiderin
Ferritin is soluble and readily mobilized; hemosiderin is insoluble and less available.
Where is ferritin mainly found?
Liver, spleen, and bone marrow.
Why is ferritin clinically important?
It is the best indicator of body iron stores.
What does low ferritin mean?
Iron deficiency.
What can high ferritin mean?
Iron overload or inflammation.
Why can ferritin increase in inflammation?
Ferritin is an acute-phase protein.
Does low ferritin always indicate iron deficiency?
Yes.
Does high ferritin always indicate iron overload?
No, it can also indicate inflammation.
What is hemosiderin made from?
Excess stored iron when ferritin storage capacity is exceeded.
How does hemosiderin appear microscopically?
Golden-brown granular pigment.
Which cells often contain hemosiderin?
Macrophages.
What is iron deficiency?
Reduced body iron stores and reduced iron availability.
Who is at high risk for iron deficiency?
Children, young women, and elderly people.
Best early marker of iron deficiency
Serum ferritin.
Why is ferritin an early marker?
It decreases before serum iron, hemoglobin, or RBC morphology changes.
Tests for iron deficiency
Serum iron, transferrin, TIBC, UIBC, transferrin saturation, ferritin, soluble transferrin receptor, reticulocyte hemoglobin.
What is Prussian blue staining used for?
Detecting iron stores in bone marrow.
What happens to soluble transferrin receptor in iron deficiency?
It increases.
What does reticulocyte hemoglobin show?
Recent iron supply to red blood cell precursors.
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, bleeding, infection, autoimmune disease, and carcinomas.
Why can infection lower serum iron?
Iron is trapped in macrophages and becomes unavailable.
Causes of high serum iron
Iron overload, decreased erythropoiesis, hepatitis, cirrhosis, and oral contraceptive use.
Why can hepatitis increase serum iron?
Damaged liver releases stored iron.
Why can decreased erythropoiesis increase serum iron?
Less iron is used for red blood cell production.
Examples of decreased erythropoiesis causes
Lead poisoning and deficiency of vitamin B12, B6, or folic acid.
Why is serum iron alone unreliable?
It changes with diet, hemolysis, supplements, infection, menstrual cycle, and circadian rhythm.
When is serum iron usually higher?
In the morning.
How much can serum iron vary during the day?
Up to about 70%.
How is serum iron measured?
Colorimetric test after releasing iron from transferrin and forming a colored complex.
What happens first in serum iron measurement?
Fe³⁺ is released from transferrin by acid treatment.
What happens after Fe³⁺ is released in serum iron measurement?
Fe³⁺ is reduced to Fe²⁺.
Which chromogen is commonly used for serum iron measurement?
Ferrozine.
What color complex forms with ferrozine?
Purple/pink complex.
What is TIBC?
Total iron binding capacity.
What does TIBC reflect?
Total capacity of transferrin to bind iron.
What happens to TIBC in iron deficiency anemia?
It increases.
Why does TIBC increase in iron deficiency?
The liver produces more transferrin to capture scarce iron.
What happens to TIBC in chronic disease?
It decreases.
What happens to TIBC in hemochromatosis?
It decreases.
What is UIBC?
Unsaturated iron binding capacity.
What does UIBC show?
Reserve capacity of transferrin to bind more iron.
What is transferrin saturation?
Percentage of transferrin binding sites occupied by iron.
Formula for transferrin saturation
Transferrin saturation (%) = 100 × serum iron / TIBC.
Iron deficiency pattern
Low serum iron, high TIBC, low transferrin saturation, low ferritin.
Iron overload pattern
High serum iron, low TIBC, high transferrin saturation, high ferritin.
What is hemosiderosis?
Iron overload without tissue damage.
Common causes of hemosiderosis
Excess iron intake, supplements, or multiple blood transfusions.
What is hemochromatosis?
Iron overload with tissue damage.
Which organs are damaged in hemochromatosis?
Liver, pancreas, heart, skin, and endocrine glands.
Typical triad of hemochromatosis
Bronze skin, cirrhosis, and diabetes mellitus.
Other signs of hemochromatosis
Cardiomyopathy, endocrine disorders, and joint disease.
What is primary hemochromatosis?
Genetic disorder causing increased intestinal iron absorption.
What is secondary hemochromatosis?
Iron overload caused by external factors.
Causes of secondary hemochromatosis
Frequent blood transfusions, excess iron therapy, or accidental ingestion of iron supplements.
Main difference between hemosiderosis and hemochromatosis
Hemosiderosis has iron overload without tissue damage; hemochromatosis has iron overload with tissue damage.