SM_249b: Iron and Anemia of Chronic Disease Flashcards
Typical diet has ____ of iron, of which ____ is absorbed
Typical diet has 10-15 mg of iron, of which 1-2 mg is absorbed
- Typical adult male has total body iron content of 4 g, most of which is in hemoglobin and myoglobin
Describe iron absorption
Iron absorption
- Non-heme source of iron -> proteolysis in stomach -> reduction via acidic environment -> absorbed through DMT-1
- Heme source of iron -> absorbed through HCP-1
____ is the major regulator of iron
Hepcidin is the major regulator of iron
- Acute phase protei
- Produced by hepatocytes, adipocytes, and macrophages
- Anti-microbial properties
Ferroportin is involved in ___
Ferroportin is involved in iron export
Hepcidin ___ iron export via ferroportin
Hepcidin prevents iron export via ferroportin
___ and ___ upregulate hepcidin production
Inflammation and iron sufficiency upregulate hepcidin production
___, ___, and ___ downregulate hepcidin production
Hypoxia, increased drive for erythroid activity, and iron deficiency downregulate hepcidin production
Iron deficiency involves ____ hepcidin
Iron deficiency involves too much hepcidin
Iron overload involves ____ hepcidin
Iron overload involves too little hepcidin
Hemochromatosis results from ___ and leads to ___
Hemochromatosis results from mutations for genes involved in hepcidin activation leading to decreased hepcidin and iron overload
IRIDA is a ____ disease resulting from ____ that causes ____ and ____
IRIDA is a recessive disease resulting from TMPRSS6 inactivation that causes increased hepcidin and iron deficiency
Great amount of iron is in the ____
Great amount of iron is in the blood
Describe assessment of iron stores
Assessment of iron stores
- Serum iron: direct measure of iron bound to transferrin (50-150 mcg/dL)
- Total iron binding capacity: measure of amount that can be bound by transferrin (300-360 mcg/dL)
- Percent saturation: iron / IBC (20-50%)
- Ferritin: measure of total body iron stores (50-200 mcg/L)
Describe stages of iron deficiency stages
Iron deficiency stages
- Iron store depletion: ferritin below reference range but iron and Hgb normal
- Iron deficient erythropoeisis: iron falls, TIBC rises, and decrease in % saturation, minimal anemia
- Iron deficiency anemia: low iron, increased IBC, low % saturation, low ferritin (often less than 10-12 mg/L) and low Hgb
Absent iron deficiency anemia is ___
Absent iron deficiency anemia is absent or reduced storage iron in reservoir (bone marrow, liver, spleen)
Functional iron deficiency anemia is ___
Functional iron deficiency anemia is when iron storage is adequate but the iron is not available for use
- Key mechanism: anemia of inflammation
- During treatment with Epo-stimulating agents: iron stores are adequate but not released into circulation rapidly enough to accomodate increased erythropoiesis
Inhibiting hepcidin ___
Inhibiting hepcidin maximizes iron availability
Iron deficiency anemia can result from ____ or ____
Iron deficiency anemia can result from increased requirements or decreased iron supply
Describe symptoms of iron deficiency anemia
Iron deficiency anemia symptoms
- Symptoms from anemia: fatigue, difficulty breathing, dizziness, and lightheadedness
- Symptoms from inability to replenish epithelial cells: brittle nails, cracking at the lips, tongue sensitivity
- Unusual symptoms: pica
- Symptoms from underlying disease process
Treatment of iron deficiency anemia involves ____, ____, and ____
Treatment of iron deficiency anemia involves treating underlying cause of present, iron supplementation (every other day), and blood transfusion in symptomatic anemia
Anemia of chronic disease is a ___ term
Anemia of chronic disease is a broad term
Inflammatory stress ___ hepcidin and leads to ___
Inflammatory stress upregulates hepcidin and limits iron availability
Describe pathogenesis of anemia of inflammation
Anemia of inflammation
- Inappropriate Epo secretion: IL-1 and TNF
- Iron sequestration: IL-6 and hepcidin
- Erythroid progenitor suppression: IL-1, TNF, and interferons
- Unknown mechanisms and shortened RBC survival
Describe symptoms of anemia of inflammation
Anemia of inflammation
- Symptoms from anemia: fatigue, difficulty breathing, dizziness, and lightheadedness
- Symptoms from an underlying disease process: inflammatory disease (RA), infection (osteomyelitis), cancer
Describe typical lab findings of anemia of inflammation
Anemia of inflammation lab findings
- Normochromic and normocytic anemia
- Mild to moderate reduction in hemoglobin (8-9.5 g/dL)
- Reduced reticulocyte count
- Inflammatory marker release: thrombocytosis, ESR, CRP, fibrinogen
In anemia of inflammation, ferritin is ____ and Epo level is ____
In anemia of inflammation, ferritin is increased and Epo level is not appropriately increased
In iron deficiency anemia, ferritin is ____ and Epo level is ____
In iron deficiency anemia, ferritin is reduced and Epo level is high
Anemia of inflammation and iron deficiency anemia can ___
Anemia of inflammation and iron deficiency anemia can coexist
Correction of underlying disease can ___ anemia of inflammation
Correction of underlying disease can improve anemia of inflammation
___ should be used to treat concurrent iron deficiency
IV iron should be used to treat concurrent iron deficiency
Hemochromatosis is ___
Hemochromatosis is excess iron loading of tissues
- Primary causes: hereditary hemochromatosis, due to mutations of genes involves in iron transport and hepcidin regulation
- Secondary causes: transfusion-associated, iron loading
Describe decreased hepcidin production
Decreased hepcidin production
- Increased drive for erythroid activity (sickle cell anemia and thalassemia) -> erythroferrone suppresses hepcidin
- Mutations in genes that regulate hepcidin (example: HFE): increased iron availability
Mutation / increased erythroid drive ___ hepcidin, leading to ___
Mutation / increased erythroid drive inhibits hepcidin, leading to excess iron availability
Describe iron studies for hemochromatosis
Hemochromatosis iron studies
Describe symptoms of hemochromatosis
Hemochromatosis symptoms
- Attributed to abnormal iron deposition
- Liver: LFT abnormalities, liver cancer
- Pancreas: diabetes
- Hypogonadism: testicular atrophy, amenorrhea
- Join destruction: particularly MCP joints
- Heart: cardiomyopathy and arrhythmia
- Skin: bronzing
- Immun system: susceptibility to Listeria, Yersinia, and vibrio actions
Hemochromatosis treatment involves ____, ____, and ____
Hemochromatosis treatment involves phlebotomy, iron chelation, and moderation of alcohol intake
Describe therapeutic uses of hepcidin
Hepcidin
- Hepcidin agonist for low hepcidin diseases (iron overload): hemochromatosis, B-thalassemia, sideroblastic anemia
- Hepcidin antagonist for high hepcidin disease (iron deficiency): anemia of inflammation, IRIDA, CKD
