other notes from hema Flashcards
Master regulatory hormone of systemic iron metabolism
Hepcidin (produced by the liver)
Effect of decreased iron stores on plasma iron
Decreases plasma iron, leading to liver alert and hepcidin production stops
Effect of decreased hepcidin production
Ferroportin in enterocyte and macrophage membranes becomes active, increasing iron absorption and recycling
Effect of increased plasma iron on hepcidin production
Plasma iron increases, iron stores increase, liver alerts and produces hepcidin
Effect of hepcidin on ferroportin
Inactivates ferroportin in enterocyte and macrophage membranes, reducing iron absorption and recycling
Hemochromatosis protein (HFE)
Hepatocyte membrane
Transferrin receptor 2 (TfR2)
Hepatocyte membrane
Bone morphogenic protein (BMP)
Secreted product of macrophages
Bone morphogenic protein receptor (BMPR)
Hepatocyte (and other cells) membrane
Hemojuvelin (HJV)
Hepatocyte membrane
SMAD (sons of mothers against decapentaplegic)
Hepatocyte (and other cells) cytoplasm
Absorption sites for iron
Duodenum and upper jejunum
Foods with high iron levels
Red meats, legumes, dark green leafy vegetables
Iron forms for absorption
Ionic iron (Fe+2, ferrous) and heme (nonionic)
Most common dietary iron form
Fe+3 (ferric), especially in plant sources, poorly absorbed
Factors inhibiting iron absorption
Oxalates, phytates, phosphates, calcium
Enhancers of iron absorption
Gastric acid, acidic foods (citrus), DcytB (duodenal cytochrome B)
Heme iron absorption
More readily absorbed than ionic iron; found in meat (myoglobin, hemoglobin)
Ferrous iron (Fe+2) transport
Carried by DMT1 (divalent metal transporter 1) across enterocyte membrane
Transport of absorbed iron
Requires ferroportin; Hephaestin reoxidizes Fe+2 to Fe+3 for transport into blood
Hephaestin function
Oxidizes iron as it exits the enterocyte for plasma transport.
Iron transport protein
Transferrin, formed when apotransferrin binds ferric (Fe+3) iron.
Receptor for transferrin
Transferrin receptor 1 (TfR1) on cell membranes.
Iron use in cells
Transferred into mitochondria for cytochrome or heme production, or stored as ferritin.
Storage form of iron in cells
Ferritin, stored in cells with excess iron, especially in macrophages and hepatocytes.
Ferritin characteristics
Intracellular protein secreted by macrophages, an acute phase reactant (APR) elevated in inflammation.
Ferritin degradation
Iron is released from ferritin by degradation in lysosomes.
Hemosiderin
Partially degraded ferritin, seen in iron overload, detectable using Prussian blue iron stain.
Iron excretion mechanism
Minimal daily loss via exfoliation; no active excretion.
Iron’s role in cells
Essential for energy production and oxygen transport in hemoglobin.
Iron recycling source
Primarily from aging RBCs degraded by splenic macrophages.
Macrophage iron storage
Stores iron from hemoglobin as ferritin.
Macrophage iron export
Uses ferroportin to export iron to other cells.
Plasma proteins in iron recycling
Haptoglobin saves hemoglobin; hemopexin saves heme.
Hepatocyte role in recycling
Exports stored iron via ferroportin to transferrin.
Main functional iron compartment in blood
Hemoglobin iron (~68%).
Functional iron in muscles
Myoglobin iron (~10%).
Functional iron in cellular enzymes
Peroxidase, catalase, cytochromes (~3%).
Primary iron storage forms
Ferritin and hemosiderin in macrophages and hepatocytes (~18%).
Iron storage exceptions in cells
Mature RBCs do not store iron.
Iron transport mechanism in plasma
Transferrin (<1%).
Serum iron reference range and use
50 to 160 μg/dL; used for diagnosing disorders of iron metabolism.
Serum iron specimen requirements
Nonhemolyzed serum, collected in the morning after 12-hour fasting.
TIBC reference range and purpose
250 to 400 μg/dL; indirectly measures transferrin concentration via iron-binding ability.
TIBC specimen requirements
Nonhemolyzed serum, 12-hour fasting; values are time-independent.
Transferrin iron saturation range and calculation
20% to 55%; (Serum Iron / TIBC) x 100.
Serum ferritin reference range for men and women
40 to 400 ng/mL (men), 12 to 160 ng/mL (women).
Significance of serum ferritin test
Reflects tissue iron stores; first indicator of declining iron storage.
Test used for direct visualization of tissue iron stores
Prussian Blue staining of bone marrow or liver biopsy.
Prussian Blue staining mechanism
Uses acidic potassium ferrocyanide; ferric iron forms visible Fe7(CN)18 (Prussian blue) compound.
Prussian Blue stain as a diagnostic tool
Gold standard for assessing tissue iron; detects hemosiderin but not ferritin.
Serum iron reference range and use
50 to 160 μg/dL; used for diagnosing disorders of iron metabolism.
Serum iron specimen requirements
Nonhemolyzed serum, collected in the morning after 12-hour fasting.
TIBC reference range and purpose
250 to 400 μg/dL; indirectly measures transferrin concentration via iron-binding ability.
TIBC specimen requirements
Nonhemolyzed serum, 12-hour fasting; values are time-independent.
Transferrin iron saturation range and calculation
20% to 55%; (Serum Iron / TIBC) x 100.
Serum ferritin reference range for men and women
40 to 400 ng/mL (men), 12 to 160 ng/mL (women).
Significance of serum ferritin test
Reflects tissue iron stores; first indicator of declining iron storage.
Test used for direct visualization of tissue iron stores
Prussian Blue staining of bone marrow or liver biopsy.
Prussian Blue staining mechanism
Uses acidic potassium ferrocyanide; ferric iron forms visible Fe7(CN)18 (Prussian blue) compound.
Prussian Blue stain as a diagnostic tool
Gold standard for assessing tissue iron; detects hemosiderin but not ferritin.
Increased tissue iron stores without tissue damage; may progress to hemochromatosis.
Hemosiderosis
Increased iron accumulation in body tissues causing tissue damage.
Hemochromatosis
Most common form of iron overload disease
Hereditary Hemochromatosis (Bronze Diabetes)
Genetic cause of Hereditary Hemochromatosis
Mutations in the HFE gene regulating dietary iron absorption
Symptoms of Hereditary Hemochromatosis
Arthritis, liver cirrhosis, congestive heart failure, impotence, bronze skin, diabetes, thyroid deficiency
Treatment approaches for Hereditary Hemochromatosis
Avoiding iron-rich foods, phlebotomy, Deferoxamine (Desferal)