Medicine – Iron Metabolism and Iron Studies

Iron is an essential trace element required for haemoglobin synthesis, oxygen transport, myoglobin function and numerous cellular enzymes. Because the body has no regulated pathway for active iron excretion, iron balance is controlled mainly by regulating intestinal absorption.

1. Total Body Iron

A normal adult contains approximately:

3–4 g of iron, though the exact amount varies with sex, body size and iron stores.

About:

Two-thirds of total body iron is present in haemoglobin.

The remainder is found mainly in:

Ferritin and haemosiderin stores.

Myoglobin.

Iron-containing enzymes.

2. Iron in Haemoglobin

Haemoglobin contains the largest functional pool of iron.

Iron is incorporated into:

Haem

within red blood cells.

Its major role is:

Reversible binding and transport of oxygen.

Therefore:

IRON DEFICIENCY → IMPAIRED HAEMOGLOBIN SYNTHESIS → MICROCYTIC HYPOCHROMIC ANAEMIA.

3. Dietary Iron Intake

The original notes state that a normal diet contains about:

20 mg iron/day

with about:

10% absorbed.

This is a reasonable traditional approximation.

In practice, daily dietary intake is often around:

10–20 mg/day,

while only approximately:

1–2 mg/day

needs to be absorbed to replace normal physiological losses.

4. Why Only a Small Amount Is Absorbed

The intestine tightly regulates iron uptake because excess iron cannot be readily excreted.

Therefore the body usually absorbs only a:

Small fraction of dietary iron.

Absorption increases when iron requirements rise, for example in:

Iron deficiency.

Pregnancy.

Increased erythropoiesis.

5. Site of Iron Absorption

Iron is absorbed mainly in the:

Duodenum and proximal jejunum.

The form of iron and the dietary environment strongly influence how efficiently it is absorbed.

6. Ferrous and Ferric Iron

The original notes correctly state:

Fe²⁺ is more readily absorbed than Fe³⁺.

Fe²⁺ = ferrous iron.

Fe³⁺ = ferric iron.

Non-haem ferric iron generally needs to be reduced to the ferrous form before efficient intestinal uptake.

Therefore:

Fe³⁺ → reduction → Fe²⁺ → intestinal absorption.

7. Role of Gastric Acid and Vitamin C

An acidic environment helps keep iron soluble and promotes conversion toward the more absorbable:

Ferrous Fe²⁺ form.

Vitamin C can also increase non-haem iron absorption by:

Reducing Fe³⁺ to Fe²⁺

and keeping iron soluble.

8. Factors That Reduce Iron Absorption

Iron absorption may be reduced by:

Phytates.

Some polyphenols, including those in tea and coffee.

Calcium in some contexts.

Reduced gastric acidity.

Inflammation through increased hepcidin.

Therefore the amount of dietary iron is not the same as the amount actually absorbed.

9. Hepcidin – Main Regulator of Iron Balance

The major hormonal regulator of systemic iron metabolism is:

Hepcidin.

Hepcidin is produced mainly by the:

Liver.

It controls iron entry into the circulation by regulating:

Ferroportin.

10. Ferroportin

Ferroportin exports iron from:

Enterocytes.

Macrophages.

Hepatocytes.

When hepcidin binds ferroportin, ferroportin is internalised and degraded.

Therefore:

↑ Hepcidin → ↓ iron absorption and ↓ iron release into plasma.

11. Hepcidin in Iron Deficiency

When iron stores are low:

Hepcidin decreases.

This allows greater ferroportin activity and therefore:

Increased intestinal iron absorption.

Increased release of stored iron.

12. Hepcidin in Inflammation

Inflammation, particularly through cytokines such as:

IL-6,

increases hepcidin production.

This traps iron inside macrophages and reduces intestinal iron absorption.

Therefore:

INFLAMMATION → ↑ HEPCIDIN → ↓ SERUM IRON DESPITE STORED IRON.

This is central to:

Anaemia of chronic inflammation.

13. Transferrin

Once iron enters the circulation, it binds mainly to:

Transferrin.

Transferrin is the principal plasma protein that:

Transports iron.

It carries iron to tissues, particularly the:

Bone marrow

for haemoglobin production.

14. Transferrin Saturation

The original notes state that transferrin is normally:

About one-third saturated.

This is a useful approximation.

Normal transferrin saturation is commonly around:

20–45%.

Therefore roughly one-quarter to one-third of available transferrin-binding sites are occupied by iron in many healthy adults.

15. Calculation of Transferrin Saturation

Transferrin saturation represents the proportion of transferrin iron-binding capacity occupied by iron.

Conceptually:

Transferrin saturation = serum iron / total iron-binding capacity × 100%.

It is especially useful when investigating:

Iron deficiency

and

Iron overload.

16. Transferrin Saturation in Iron Deficiency

In iron deficiency:

Serum iron falls.

Transferrin/TIBC often rises.

Therefore:

Transferrin saturation falls.

A low transferrin saturation supports:

Insufficient circulating iron available for erythropoiesis.

17. Transferrin Saturation in Iron Overload

In iron overload, more transferrin-binding sites become occupied.

Therefore:

Transferrin saturation rises.

Persistently high saturation is an important clue to:

Hereditary haemochromatosis

or other iron-loading states.

18. Ferritin

Ferritin is the major intracellular iron-storage protein.

Serum ferritin broadly reflects:

Body iron stores.

Therefore:

Low ferritin → strongly suggests iron deficiency.

High ferritin → may indicate iron overload.

However, interpretation is more complicated when inflammation is present.

19. Ferritin in Iron Deficiency

A reduced ferritin is one of the most useful findings in diagnosing:

Iron deficiency.

It indicates depletion of:

Stored iron.

Therefore:

LOW FERRITIN = IRON DEFICIENCY UNTIL PROVEN OTHERWISE, provided there is no unusual laboratory issue.

20. Ferritin in Iron Overload

Ferritin may rise when iron stores increase.

Examples include:

Hereditary haemochromatosis.

Repeated transfusions.

Other secondary iron-loading disorders.

However, ferritin alone cannot prove true iron overload.

21. Ferritin as an Acute-Phase Reactant

The original notes correctly state that ferritin is also raised in:

Acute and chronic inflammation.

Ferritin can increase with:

Infection.

Inflammatory disease.

Liver injury.

Malignancy.

Therefore:

HIGH FERRITIN ≠ AUTOMATICALLY HIGH IRON STORES.

22. Ferritin in Chronic Inflammation

A patient with inflammation may have:

Normal or high ferritin

despite having insufficient iron available for red-cell production.

This occurs because inflammation increases:

Hepcidin.

Iron becomes trapped within storage cells.

Therefore:

Ferritin may look adequate while serum iron and transferrin saturation are low.

23. Plasma or Serum Iron

The original notes correctly state:

Plasma iron varies.

Serum iron can fluctuate significantly during the day and is influenced by:

Recent dietary intake.

Inflammation.

Time of sampling.

Iron supplementation.

Therefore serum iron by itself is:

Not a reliable measure of total body iron stores.

24. Why Serum Iron Should Not Be Used Alone

A patient with iron deficiency may occasionally have a serum iron that is not profoundly reduced.

Conversely, a patient with inflammation may have low serum iron despite adequate or increased body iron stores.

Therefore iron status is better assessed using a combination of:

Ferritin.

Transferrin or TIBC.

Transferrin saturation.

Full blood count and red-cell indices.

25. Iron Deficiency – Typical Iron Study Pattern

A typical pattern is:

Ferritin ↓.

Serum iron ↓.

Transferrin/TIBC ↑.

Transferrin saturation ↓.

As deficiency progresses:

MCV ↓

and

MCH ↓.

This produces:

Microcytic hypochromic anaemia.

26. Iron Overload – Typical Pattern

Iron overload commonly produces:

Ferritin ↑.

Serum iron ↑.

Transferrin saturation ↑.

TIBC/transferrin may be normal or reduced depending on the underlying condition.

In hereditary haemochromatosis, a particularly useful early clue is:

Raised transferrin saturation.

27. Anaemia of Chronic Inflammation – Typical Pattern

Inflammation causes:

↑ Hepcidin.

Therefore iron becomes less available to the marrow.

Typical findings include:

Serum iron ↓.

Transferrin/TIBC ↓ or normal.

Transferrin saturation ↓.

Ferritin normal or ↑.

This differs importantly from uncomplicated iron deficiency.

28. Iron Recycling

Most iron used each day for new red-cell production does not come directly from the diet.

Instead, it comes from:

Recycling of old red blood cells.

Macrophages break down senescent erythrocytes and recover iron from:

Haemoglobin.

That iron is returned to plasma through:

Ferroportin

and carried by:

Transferrin.

29. Daily Iron Turnover

The bone marrow requires a much larger amount of iron each day for erythropoiesis than is absorbed from the gut.

Most of this requirement is supplied by:

Macrophage recycling.

Only the small amount lost from the body needs to be replaced by:

Intestinal absorption.

30. Body Iron – Note Form

Total body iron:

Approximately 3–4 g in a typical adult.

About two-thirds:

Contained within haemoglobin.

Remaining iron:

Ferritin/haemosiderin stores.

Myoglobin.

Enzymes.

31. Dietary Iron – Note Form

Dietary intake:

Approximately 10–20 mg/day in many diets.

↓

Only a small fraction absorbed.

↓

Approximately 1–2 mg/day normally enters the body.

Main absorption site:

Duodenum/proximal jejunum.

32. Ferrous Versus Ferric Iron – Note Form

Fe²⁺ = ferrous iron.

More readily absorbed.

Fe³⁺ = ferric iron.

Usually must be reduced before efficient absorption.

Therefore:

Fe³⁺ → Fe²⁺ → intestinal uptake.

33. Transferrin – Note Form

Function:

Transports iron in plasma.

Normal saturation:

Approximately 20–45%, traditionally described as about one-third saturated.

Iron deficiency:

Transferrin saturation ↓.

Iron overload:

Transferrin saturation ↑.

34. Ferritin – Note Form

Ferritin = storage protein.

Iron deficiency:

Ferritin ↓.

Iron overload:

Ferritin often ↑.

Inflammation/infection/liver disease:

Ferritin may also ↑.

Therefore:

Ferritin must be interpreted in clinical context.

35. Serum Iron – Note Form

Serum iron varies considerably.

Therefore it should:

Not be interpreted alone.

Use it with:

Ferritin + transferrin/TIBC + transferrin saturation.

36. Important Clarifications to the Original Notes

The statement:

“4 g in the normal human body”

is a reasonable traditional approximation, but total body iron varies. A practical modern figure is:

Approximately 3–4 g in a typical adult.

The statement:

“20 mg/day in normal diet; only 10% absorbed”

is also a useful approximation.

The more physiologically important point is that only around:

1–2 mg/day normally needs to be absorbed

because most iron is continuously recycled from old red cells.

The statement:

“Fe²⁺ more readily absorbed than Fe³⁺”

is correct.

The statement:

“Transferrin one-third saturated normally”

is a useful approximation; typical laboratory ranges are around:

20–45%.

The statement:

“Ferritin increased in iron overload, decreased in deficiency”

is correct, but remember:

Ferritin is an acute-phase reactant.

Therefore inflammation can produce:

High ferritin even when circulating available iron is low.

Key Clinical Pattern

For rapid recall:

HAEMOGLOBIN = MAIN BODY IRON POOL.

TRANSFERRIN = IRON TRANSPORT.

FERRITIN = IRON STORAGE.

HEPCIDIN = MASTER REGULATOR OF IRON ENTRY INTO PLASMA.

Fe²⁺ IS ABSORBED MORE EASILY THAN Fe³⁺.

For iron studies:

IRON DEFICIENCY → ↓ ferritin + ↓ serum iron + ↑ TIBC/transferrin + ↓ transferrin saturation.

IRON OVERLOAD → ↑ ferritin + ↑ transferrin saturation.

CHRONIC INFLAMMATION → ↓ serum iron + ↓/normal transferrin + normal/↑ ferritin.