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Questions and Answers
What percentage of iron in the human body is found in hemoglobin?
What percentage of iron in the human body is found in hemoglobin?
What is the primary form of dietary iron that is most easily absorbed?
What is the primary form of dietary iron that is most easily absorbed?
What amount of iron is typically lost daily through normal shedding of cells?
What amount of iron is typically lost daily through normal shedding of cells?
What additional iron requirement is there for pregnant and lactating women?
What additional iron requirement is there for pregnant and lactating women?
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Which enzyme converts ferric iron to ferrous iron in the absorption process?
Which enzyme converts ferric iron to ferrous iron in the absorption process?
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What is the average daily requirement of iron for men and postmenopausal women?
What is the average daily requirement of iron for men and postmenopausal women?
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In what state must most dietary iron be converted before absorption?
In what state must most dietary iron be converted before absorption?
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What is the typical absorption percentage of iron from a healthy diet?
What is the typical absorption percentage of iron from a healthy diet?
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What condition is characterized by a progressive increase in iron stores, leading to organ impairment and damage?
What condition is characterized by a progressive increase in iron stores, leading to organ impairment and damage?
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In hereditary hemochromatosis, what is the expected value for transferrin saturation?
In hereditary hemochromatosis, what is the expected value for transferrin saturation?
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What does TIBC measure in relation to transferrin?
What does TIBC measure in relation to transferrin?
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Which factor primarily controls iron absorption in the body?
Which factor primarily controls iron absorption in the body?
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Which test is considered the largest pool of body iron and is part of the complete blood count (CBC)?
Which test is considered the largest pool of body iron and is part of the complete blood count (CBC)?
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What role does hepcidin play in iron metabolism?
What role does hepcidin play in iron metabolism?
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What might cause low TIBC values in individuals?
What might cause low TIBC values in individuals?
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Which of the following conditions is NOT associated with increased iron absorption?
Which of the following conditions is NOT associated with increased iron absorption?
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What is a common lab finding in patients with iron deficiency anemia?
What is a common lab finding in patients with iron deficiency anemia?
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How is transferrin saturation calculated?
How is transferrin saturation calculated?
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In iron deficiency anemia, red blood cells are typically characterized as:
In iron deficiency anemia, red blood cells are typically characterized as:
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Which of the following is NOT a primary method for measuring iron metabolism in the clinical laboratory?
Which of the following is NOT a primary method for measuring iron metabolism in the clinical laboratory?
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What condition can result in acquired hemochromatosis due to ineffective erythropoiesis?
What condition can result in acquired hemochromatosis due to ineffective erythropoiesis?
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Which of the following groups is most likely to experience iron deficiency?
Which of the following groups is most likely to experience iron deficiency?
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What is the main characteristic of hemosiderin in liver cells as seen by Prussian blue stain?
What is the main characteristic of hemosiderin in liver cells as seen by Prussian blue stain?
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What indicates a fully developed iron deficiency anemia in laboratory tests?
What indicates a fully developed iron deficiency anemia in laboratory tests?
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What is the main way heme iron is absorbed by the body?
What is the main way heme iron is absorbed by the body?
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Which substance is known to decrease iron absorption due to forming insoluble complexes?
Which substance is known to decrease iron absorption due to forming insoluble complexes?
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What role does transferrin play in the body?
What role does transferrin play in the body?
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Where is the majority of absorbed iron utilized in the body?
Where is the majority of absorbed iron utilized in the body?
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Which of the following accurately describes ferritin?
Which of the following accurately describes ferritin?
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What is hemosiderin, and how does it differ from ferritin?
What is hemosiderin, and how does it differ from ferritin?
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Approximately how much iron is derived from the destruction of old erythrocytes daily?
Approximately how much iron is derived from the destruction of old erythrocytes daily?
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What percentage of transferrin's binding sites for Fe3+ are typically saturated?
What percentage of transferrin's binding sites for Fe3+ are typically saturated?
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Study Notes
Iron & Porphyrin Metabolism
- Iron is the most abundant element on Earth, but only trace amounts are present in living cells.
- Iron in the human body is largely found in the porphyrin ring of heme, incorporated into proteins like hemoglobin, myoglobin, catalase, peroxidases, and cytochromes.
- An average adult male/female has 4–5 grams of iron in their body.
- Iron is distributed as hemoglobin (65-70%), myoglobin (10%), and enzymes (other), with 20–25% in storage.
- Daily iron requirement depends on age, gender, and physiological status.
- About 1 mg iron is lost daily through shedding epithelial cells and cells lining the gastrointestinal and urinary tracts.
- Small numbers of erythrocytes are lost in urine and feces.
- Absorption of 1 mg of iron per day is enough for men and post-menopausal women.
- Blood lost during each menstrual cycle can contain 20-40 mg iron.
- Women of reproductive age need to absorb 2 mg iron per day.
- The growing fetus, blood loss during delivery, and feeding an infant need additional 1 gram iron.
- Increased daily iron demands occur in pregnant and lactating women (3-4 mg/day).
- Absorbable dietary iron comes in two forms: heme and non-heme iron.
- Heme iron comes from hemoglobin and myoglobin in animal food sources (meat, seafood, poultry).
- Heme iron is easily absorbed (15-35%) contributing 10% or more of total absorbed iron.
- Non-heme iron comes from plants and fortified foods and is less well absorbed.
- A healthy diet usually has 10-20 mg iron daily, with only 5-10% absorbed primarily in the duodenum and upper small intestine.
- Most dietary iron is ferric (Fe3+), needing conversion to ferrous (Fe2+) to enter epithelial cells.
- Ferric iron is converted to ferrous iron by the brush border enzyme, ferric reductase.
- Ferrous iron is transported into cells by divalent metal transporter (DMP).
- Substances like phosphates (in eggs, cheese, milk), oxalates, and phytates (in vegetables), and tannates (in tea) form insoluble complexes with iron, decreasing absorption.
- Heme iron is absorbed through a different mechanism.
- Heme iron is directly absorbed by cells.
- In the epithelial cells, the porphyrin ring is broken, liberating iron.
- This process is more efficient than non-heme iron absorption.
- In intestinal epithelial cells, iron is incorporated into ferritin for storage, or transported across the basolateral surface into blood.
- Absorbed iron is a fraction of the iron required for heme synthesis.
- The breakdown of old erythrocytes by tissue macrophages (particularly in spleen) provides 20-25 mg iron per day.
- Iron binds to transferrin and is transported to bone marrow for heme synthesis.
- Free iron is toxic to cells and biomolecules; iron is transported bound to specific proteins.
- Transferrin is the iron transport protein in the blood.
- Each transferrin has two binding sites for Fe3+, typically 20-50% saturated.
- Transferrin carries iron to cells needing it.
- Holotransferrin binds to its receptor on cell surface, getting internalized, and releases its iron into the cell.
- The transferrin-receptor complex is taken into the cell via endocytosis.
- An acidic medium inside the vesicle releases iron from transferrin.
- Iron is used for heme synthesis or stored as ferritin.
- Iron is stored in tissues as ferritin or hemosiderin.
- Ferritin is present in most cells and is readily mobilized storage iron.
- Hemosiderin is an insoluble complex derived from ferritin, found in granules with higher iron concentration but releases iron more slowly.
- About one-third of the body's iron reserve is stored in the liver, one-third in the bone marrow, and the rest in the spleen and other tissues.
- Because iron loss is continuous, iron balance is controlled by changes in absorption.
- Major factors affecting iron absorption include body iron stores and red blood cell production rate.
- Absorption is mainly controlled by hepatic hormone hepcidin interacting with ferroportin.
- Ferroportin is expressed in iron-storing and transporting tissues and acts as both hepcidin receptor and the sole cellular exporter of iron.
- Conditions stimulating iron absorption include iron deficiency, pregnancy, and accelerated erythropoiesis.
Pathological Conditions
- Iron deficiency is the most frequent nutritional disorder in humans and the most common cause of anemia.
- Iron deficiency is more frequent in women and people with low socioeconomic status, patients after gastrointestinal surgery, and those with chronic diarrhea.
- Iron deficiency develops in stages. When iron reserves are depleted, iron metabolism tests become abnormal, even before anemia appears.
- In iron deficiency, hemoglobin (Hb) concentration decreases, and red blood cells become paler (hypochromic).
- In full-blown iron deficiency anemia, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) also decrease.
- Examination of peripheral blood smears shows hypochromia, microcytosis, and anisocytosis (abnormal erythrocyte size and shape.).
- Lab tests distinguish iron deficiency from other hypochromic, microcytic anemias.
- Serum iron is usually low.
- Total Iron Binding Capacity (TIBC) is usually high.
- Transferrin saturation is usually low.
- Serum ferritin is usually low.
- Free Erythrocyte Protoporphyrin (FEP) is usually high.
- TIBC measures the total amount of iron-binding capacity in the blood (primarily governed by transferrin).
- Transferrin saturation is calculated by dividing serum iron concentration by TIBC.
- Transferrin saturation provides an estimate of how many transferrin iron-binding sites are occupied.
Hereditary Hemochromatosis
- Hereditary hemochromatosis is a genetic disorder causing an increase in iron stores, leading to organ damage.
- Patients with hereditary hemochromatosis may absorb 4 mg or more iron per day, even on a usual diet.
- Excessive iron is deposited in the liver, pancreas, heart, skin, and other organs.
- In hereditary hemochromatosis, serum iron is high, TIBC is low, and transferrin saturation is high.
Iron Overload
- Iron overload can also be acquired due to ineffective erythropoiesis or multiple blood transfusions.
- Medicinal iron supplements do not usually lead to hemochromatosis.
Laboratory Tools for Iron Metabolism
- Clinical laboratories measure three iron compartments (about 90% of total iron): Hemoglobin (measured in CBC), serum iron/transferrin, and serum ferritin to identify iron metabolism disorders.
Complete Blood Count (CBC)
- A CBC provides erythrocyte count, hemoglobin concentration, and red blood cell indices.
- The World Health Organization (WHO) defines anemia as a hemoglobin concentration below 13 g/dL in males, 12 g/dL in females, and 11 g/dL in pregnant women.
- Iron deficiency causes hypochromic, microcytic anemia, reducing MCV, MCH, and MCHC.
- Other causes of hypochromic, microcytic anemia also include thalassemia trait, sideroblastic anemia, and anemia of chronic disease.
- Red blood cell parameters may show signs of anemia but not necessarily the cause.
Serum Iron, TIBC, & Transferrin Saturation Measurements
- Serum iron concentration can fluctuate, even in healthy people.
- This daily variation limits the diagnostic usefulness of a single serum iron measurement.
- Serum iron, TIBC, and transferrin saturation should ideally be measured together.
- TIBC measures the maximum amount of iron that serum proteins can bind.
Serum Ferritin
- Low serum ferritin accurately reflects low storage iron levels, indicating possible iron deficiency before other measurements change.
- A higher value might indicate iron overload.
Heme Synthesis & the Porphyrias
Structure & Function
- Porphyrins are macrocyclic molecules with a ring structure consisting of four pyrrole units joined by methenyl bridges.
- The arrangement of four nitrogens allows porphyrins to chelate metal atoms.
Heme Synthesis Metabolism
- Heme synthesis occurs in all cells, primarily in the bone marrow (red blood cell precursors) and liver.
- The synthetic pathway starts with the condensation of succinyl CoA and glycine to form porphobilinogen (PBG).
- PBG is a pyrrole with acetate and propionate side chains at its corners.
Porphyrias
- Porphyrias are genetically determined disorders of heme synthesis, caused by a deficiency in seven enzymes involved in heme synthesis.
- Many porphyrias are inherited as autosomal dominant traits.
- Porphyrin levels behind deficient enzymes accumulate and pass into body tissues and fluids.
- Excess porphyrins and their precursors are excreted in urine or feces, used for diagnosis.
Neurological Porphyrias
- Four porphyrias are characterized by acute attacks of abdominal pain, neurological, and/or psychiatric disturbances.
- These include acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and ALA dehydratase deficiency.
- Attacks are sometimes accompanied by increased ALA and PBG excretion in urine.
Cutaneous Porphyrias
- The three cutaneous porphyrias cause an excess of porphyrins in tissues, especially the skin.
- Features include photosensitivity and skin lesions.
- Porphyria Cutanea Tarda is the most common type, caused by partial deficiency in uroporphyrinogen decarboxylase.
Delta-Aminolevulinic Acid (ALA) Levels
- Urine ALA values are elevated in all neurological porphyrias and increased in lead poisoning.
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Test your knowledge on iron and porphyrin metabolism in the human body. Explore topics such as iron distribution, daily requirements, and the importance of iron in various proteins. Perfect for biology students looking to deepen their understanding of this essential element.
