Iron Deficiency Anemia and Hemochromatosis Quiz
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Questions and Answers

Which of the following is NOT a characteristic of iron deficiency anemia?

  • Hypochromia and microcytosis
  • High plasma ferritin (correct)
  • Elevated Transferrin
  • Low iron levels

    • What is a common outcome associated with genetic hemochromatosis?

  • Decreased gut absorption of iron
  • Low iron absorption
  • Increased hepcidin levels
  • Liver cirrhosis and disease (correct)

    • Which of the following mechanisms contributes to iron overload in genetic hemochromatosis?

  • Increased DMT1 and DcytB activity (correct)
  • Decreased activity of ferroportin
  • Low absorption of iron from the gut
  • High levels of hepcidin

    • What distinguishes anemia of chronic disease from iron deficiency anemia?

    <p>Increased hepcidin levels</p> Signup and view all the answers

    Which type of iron studies would NOT be indicative of iron overload?

    <p>Low serum iron</p> Signup and view all the answers

    What is the relationship between serum iron levels and the menstrual cycle?

    <p>Serum iron levels are lower during menstruation than prior to it.</p> Signup and view all the answers

    How is transferrin saturation calculated?

    <p>Transferrin saturation = 100 x serum iron / TIBC</p> Signup and view all the answers

    What does a low serum ferritin level most specifically indicate?

    <p>Iron deficiency</p> Signup and view all the answers

    Which of the following statements regarding ferritin measurement is true?

    <p>Ferritin levels can be elevated due to acute phase response.</p> Signup and view all the answers

    Which statement about the total iron binding capacity (TIBC) is correct?

    <p>TIBC is directly related to transferrin concentration.</p> Signup and view all the answers

    What is a significant factor affecting plasma iron levels in pregnant women?

    <p>Plasma iron levels may be elevated and should occur.</p> Signup and view all the answers

    How much iron do women typically lose per day during their menstrual cycle?

    <p>1.4 to 3.4 mg</p> Signup and view all the answers

    Which component of ferritin is responsible for iron storage?

    <p>Iron-phosphate-hydroxide core</p> Signup and view all the answers

    What role does hepcidin play in iron metabolism?

    <p>Inhibits iron release from cells</p> Signup and view all the answers

    Which protein is required in the gut to oxidize iron for binding to transferrin?

    <p>Hephaestin</p> Signup and view all the answers

    What is a likely consequence of high levels of soluble transferrin receptors?

    <p>Iron deficiency</p> Signup and view all the answers

    What happens to transferrin after it donates iron to the mitochondria?

    <p>It is recycled back to the plasma</p> Signup and view all the answers

    Which of the following statements is true regarding the internalization cycle of transferrin?

    <p>Receptor and transferrin are endocytosed together</p> Signup and view all the answers

    Which metal ion is known to interfere with iron uptake by both hepatocytes and erythrocytes, leading to anemia?

    <p>Aluminum</p> Signup and view all the answers

    Which hemoglobin type accounts for the highest percentage of total hemoglobins in the human body?

    <p>Hb-A1</p> Signup and view all the answers

    Which transporter is responsible for releasing iron into the cell after endocytosis of the transferrin-receptor complex?

    <p>DMT1</p> Signup and view all the answers

    Why might soluble transferrin receptors be elevated in a patient with inflammation?

    <p>In response to iron deficiency</p> Signup and view all the answers

    What is a common biochemical parameter indicating iron deficiency?

    <p>Low plasma iron levels</p> Signup and view all the answers

    What does the term 'iron scavenging' refer to in the context of intravascular hemolysis?

    <p>Iron conservation mechanisms</p> Signup and view all the answers

    What is the primary function of ferritin in iron metabolism?

    <p>To store and release iron as needed</p> Signup and view all the answers

    What does the binding constant ($K_a$) relate to in the transferrin-receptor interaction?

    <p>The affinity between transferrin and its receptor</p> Signup and view all the answers

    Which of the following metabolic pathways involves the transformation of hemoglobin to bilirubin?

    <p>Hb → Fe + Protoporphyrin</p> Signup and view all the answers

    Which physiological condition can lead to increased iron demands, potentially causing iron deficiency?

    <p>Pregnancy</p> Signup and view all the answers

    How does Chromium toxicity affect hemoglobin levels?

    <p>Interferes with iron uptake, leading to anemia</p> Signup and view all the answers

    Which process is primarily responsible for the recovery of iron from old red blood cells?

    <p>Macrophage digestion</p> Signup and view all the answers

    Which of the following is NOT a type of hemoglobin mentioned?

    <p>Apo-Hb</p> Signup and view all the answers

    What key factor must be identified when diagnosing iron deficiency?

    <p>Underlying cause</p> Signup and view all the answers

    What is the primary function of hepcidin in iron regulation?

    <p>Inactivates ferroportin to reduce iron release</p> Signup and view all the answers

    Which amino acids are involved in the synthesis of aminolevulinic acid?

    <p>Glycine and Succinyl CoA</p> Signup and view all the answers

    What is the immediate product of two molecules of aminolevulinic acid in heme synthesis?

    <p>Porphobilinogen</p> Signup and view all the answers

    What is one consequence of increased hepcidin levels?

    <p>Decreased iron absorption from the gut</p> Signup and view all the answers

    Which of the following is NOT a step in the synthesis of heme?

    <p>Formation of Hemoglobin from Uroporphyrinogen III</p> Signup and view all the answers

    Which process does not occur as a direct result of hepcidin activity?

    <p>Promotion of apoptosis in gut enterocytes</p> Signup and view all the answers

    What is the final product formed when Protoporphyrin IX reacts with iron?

    <p>Heme</p> Signup and view all the answers

    Which of the following statements about hepcidin is true?

    <p>It possesses antimicrobial activity</p> Signup and view all the answers

    Which step in heme synthesis occurs after Uroporphyrinogen III?

    <p>Formation of Coproporphyrinogen III</p> Signup and view all the answers

    Study Notes

    Plasma Iron

    • Iron concentration changes throughout the day, highest in the morning.
    • During the menstrual cycle, serum iron levels are lower than before the cycle.
    • Women lose 104 to 3.4 mg of iron per day during their menstrual cycle.
    • 50% of women lose 1.4 mg/day, 25% lose 1.7 mg per day, and another 25% lose 3.2 mg per day
    • Elevated plasma iron in pregnant women is a normal occurrence.

    Plasma Iron Calculations

    • Transferrin = 0.7 x TIBC (µg/dL)
    • TIBC = 1.43 x Transferrin (mg/dL)
    • Transferrin saturation = 100 x (serum iron / TIBC)
    • TIBC stands for Total Iron Binding Capacity

    Iron Storage - Ferritin

    • Ferritin stores iron in the liver and other cells.
    • Molecular weight (MW) is 460,000.
    • The outer shell of ferritin (apoferritin) consists of 22 protein subunits.
    • An iron-phosphate-hydroxide core is at the center of the molecule.
    • Ferritin contains 20% iron by weight and can bind up to 4,500 iron atoms per molecule.
    • Only a small fraction of ferritin is found in the bloodstream (less than 1% of serum iron).
    • Iron is stored and released in a controlled way by ferritin.

    Plasma Ferritin

    • Plasma ferritin is an iron storage protein.
    • It contains iron and apo-ferritin.
    • Apo-ferritin has 24 subunits.
    • Ferritin molecules have 4000 iron atoms each.
    • Measuring plasma ferritin levels is essential for diagnosing iron-related conditions, especially low or high iron levels in patients.
    • This is also useful for diagnosing patients with anemia resulting from infections or those with elevated plasma iron.

    Ferritin Measurement

    • Ferritin levels reflect stored iron.
    • Low ferritin levels indicate iron deficiency, a highly reliable finding.
    • Elevated ferritin levels can indicate iron overload.
    • Ferritin levels can be raised by the release of ferritin from damaged tissues, like in hepatitis, leukemia, or lymphoma.
    • Acute phase reactions (caused by infection, tissue damage, and cancer) can also cause increased ferritin.

    Iron Release from Cells

    • Ferroportin is a protein on the cell surface that releases iron.
    • Ferroportin is located on gut cells, liver cells, and macrophages.
    • A cofactor is needed to oxidize iron to allow binding to transferrin.
    • Hephaestin is in the gut, and caeruloplasmin is in other cells helping with iron release.
    • Hepcidin prevents iron release from cells, and this is linked to chronic disease anemia.

    Iron Uptake by Cells

    • Transferrin, carrying iron, binds to receptors on hepatocytes and erythrocytes.
    • The transferrin-receptor complex is internalized into the cell.
    • Transferrin releases iron into the mitochondria, where it's used in heme synthesis.
    • Ferritin absorbs released iron for enzyme and other protein synthesis.
    • The transferrin receptor is then released from the cell.

    Transferrin Receptors

    • Transferrin receptors collect iron from transferrin.
    • They recognize and bind to transferrin before internalization into the cells.
    • Iron is released inside the cell using the Iron transporter DMT1.
    • The receptor returns to the cell surface, and transferrin is released.

    Solvable Transferrin Receptors

    • Soluble transferrin receptors are truncated forms of cell-surface receptors found circulating in the blood.
    • High levels are indicative of iron deficiency, while low levels often accompany iron overload.
    • They might aid in diagnosing iron deficiency, particularly in inflammatory conditions.
    • They aren't routinely used for testing now.

    Intracellular Movement of Iron

    • Fe-apotransferrin binds to transferrin receptors on cell membranes.
    • Transferrin and the receptor form a complex (Tf-receptor).
    • The binding constant (Ka) for this complex is 10^-7.

    Internalization Cycle of Transferrin

    • Transferrin binds to the receptor.
    • Transferrin is internalized into the cell.
    • Iron is released from transferrin.
    • Transferrin-apotransferrin is exocytosed from the cell and returns to the plasma.
    • Apotransferrin is released from the receptor to transport to the intestine. Iron can be brought to the mitochondria.
    • Some iron enters ferritin for storage.

    Hepcidin

    • Hepcidin is a 25 amino acid peptide.
    • Identified in 2000.
    • It has antimicrobial activity and is produced by the liver.
    • Hepcidin is a master iron regulatory hormone.
    • Hepcidin deactivates ferroportin, thus reducing iron release from cells.
    • Low hepcidin levels can increase iron absorption in the gut, and this often leads to high levels of iron in the body.
    • High hepcidin levels can decrease iron absorption.

    Heme Synthesis

    • Heme biosynthesis involves a series of enzymatic reactions.
    • Amino-levulinic acid (ALA) is a crucial starting material.
    • It leads to the production of porphyrinogens from multiple steps until the final step where protoporphyrin combines with iron to form heme.
    • Various articles and publications related to aluminum/chromium toxicity, their effects on heme synthesis, and protein synthesis and plasma iron have been referenced.

    Interference of Metal Ions with Heme Synthesis

    • Aluminum interferes with iron uptake by hepatocytes and erythrocytes leading to anemia.
    • Cadmium also interferes with iron uptake by hepatocytes.
    • Lead (Pb) can disrupt heme synthesis.
    • Toxicity from chromium and zinc also contribute to anemia.

    Hemoglobins

    • Hemoglobin structure/ types are noted, along with their percentage presence in the body.

    Hemoglobins (Continued)

    • Other types of hemoglobin are listed

    Iron Scavenging

    • Intravascular hemolysis is the breakdown of red blood cells within the blood vessels.
    • Free hemoglobin combines with haptoglobins in the blood.
    • The complex is taken up by the liver.
    • Free haem combines with hemopexin.
    • Haemopexin-bound haem is taken up by the liver.
    • Haem passing through the kidneys is reabsorbed.
    • These mechanisms help to maintain iron balance in the body, particularly in pathological situations.

    Iron Re-use

    • Old red blood cells are broken down in macrophages, located in the spleen and other organs
    • Recovered iron is transported to the liver and other storage sites.
    • Iron from old red blood cells is re-used.
    • Very little iron is lost via routine metabolism.

    Bilirubin

    • Hemoglobin is broken down to iron and protoporphyrin.
    • Protoporphyrin is converted into biliverdin.
    • Biliverdin is further converted into bilirubin.
    • Bilirubin binds to albumin.
    • Bilirubin is processed in the liver and then eliminated via the bile.

    Iron Deficiency

    • Iron deficiency can arise from decreased iron intake, increased iron loss, or increased iron demand.
    • Iron stores are depleted before signs of deficiency are noticeable.
    • Conditions causing iron deficiency must be addressed first before diagnosing iron deficiency.
    • Biochemical parameters include high TIBC, low ferritin, and low plasma iron levels.

    Iron Deficiency (Continued)

    • Iron deficiency is common but not a diagnosis in itself.
    • The underlying reason(s), such as low intake, malabsorption, or blood loss, needs to be investigated.
    • This can relate to obstetric causes, inflammatory bowel disease, or bowel issues.

    Iron Deficiency (continued)

    • Laboratory findings for iron deficiency show low iron, low ferritin, elevated transferrin, and low transferrin saturation.

    Iron Overload

    • Iron overload can result from high iron intake, intravenous injections, or hemochromatosis.
    • High plasma iron levels are accompanied by high transferrin saturation and high plasma ferritin levels.

    Hemochromatosis

    • Hemochromatosis is a rare disease.
    • Excessive iron absorption is a characteristic feature.
    • Hemosiderin appears in the skin.
    • Liver damage, pancreatic dysfunction, diabetes, and heart problems can occur.

    Genetic Hemochromatosis

    • Genetic hemochromatosis is an iron overload disease.
    • Caused by increased iron absorption.
    • This condition may lead to progressive liver damage (cirrhosis) and eventually affect other organs.

    Genetic Hemochromatosis (continued)

    • The most common genetic hemochromatosis is caused by mutations in the HFE gene (C282Y).
    • These mutations lead to low hepcidin levels and excessive ferroportin activity.
    • Increased gut iron absorption also contributes to the condition.
    • Other mechanisms, including DMT1 and DcytB activity, may also be involved. This type of hemochromatosis has a variable penetrance, meaning the expression of the disease can vary from person to person.

    Genetic Hemochromatosis (continued)

    • Different types of genetic hemochromatosis are related to different genes.

    Anemia of Chronic Disease

    • Anemia of chronic disease is associated with conditions like infection, inflammation, or cancer.
    • Decreased iron absorption, low serum iron, and iron storage in cells are seen.
    • Hepcidin, an acute-phase protein, is increased in the blood and impedes iron absorption by restricting the iron release from cells.

    Anemia of Chronic Disease (continued)

    • Anemia of chronic disease shares some symptoms with iron deficiency anemia, but the treatments differ significantly.
    • Ferritin, iron, and transferrin levels can be misleading as they can be elevated, decreased, or normal in this type of anemia.
    • Hemoglobin levels are commonly low in iron-deficient anemia.
    • Mean cell volume (MCV) is usually low in iron deficiency.
    • Liver iron levels are high in iron overload diseases and may be a better marker for detecting hereditary hemochromatosis than standard iron indices, especially when corrected for age.
    • Bone marrow iron helps detect if iron is depleted in the person.

    Future Possibilities

    • Treatment with hepcidin could be effective in managing iron overload.
    • Research is underway on methods to block hepcidin for conditions like anemia of chronic disease.
    • Diagnostic tools based on hepcidin could offer more accurate and precise diagnoses.

    Conclusions

    • Iron-related diseases are common and clinically important.
    • Recent advances have significantly improved iron-related disease understanding, diagnosis, and management.
    • Iron studies are crucial initial assessments.
    • New techniques and therapeutics will likely evolve based on these improvements.

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    Plasma Iron Section 3 - PDF

    Description

    This quiz covers key concepts related to iron deficiency anemia and genetic hemochromatosis. It explores mechanisms of iron overload, iron studies, and factors affecting plasma iron levels. Test your knowledge on the characteristics and clinical implications of these conditions.

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