SM_249b: Iron and Anemia of Chronic Disease

Question 1

Typical diet has ____ of iron, of which ____ is absorbed

Answer 1

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

Question 2

Describe iron absorption

Answer 2

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

Question 3

____ is the major regulator of iron

Answer 3

Hepcidin is the major regulator of iron

• Acute phase protei
• Produced by hepatocytes, adipocytes, and macrophages
• Anti-microbial properties

Question 4

Ferroportin is involved in ___

Answer 4

Ferroportin is involved in iron export

Question 5

Hepcidin ___ iron export via ferroportin

Answer 5

Hepcidin prevents iron export via ferroportin

Question 6

___ and ___ upregulate hepcidin production

Answer 6

Inflammation and iron sufficiency upregulate hepcidin production

Question 7

___, ___, and ___ downregulate hepcidin production

Answer 7

Hypoxia, increased drive for erythroid activity, and iron deficiency downregulate hepcidin production

Question 8

Iron deficiency involves ____ hepcidin

Answer 8

Iron deficiency involves too much hepcidin

Question 9

Iron overload involves ____ hepcidin

Answer 9

Iron overload involves too little hepcidin

Question 10

Hemochromatosis results from ___ and leads to ___

Answer 10

Hemochromatosis results from mutations for genes involved in hepcidin activation leading to decreased hepcidin and iron overload

Question 11

IRIDA is a ____ disease resulting from ____ that causes ____ and ____

Answer 11

IRIDA is a recessive disease resulting from TMPRSS6 inactivation that causes increased hepcidin and iron deficiency

Question 12

Great amount of iron is in the ____

Answer 12

Great amount of iron is in the blood

Question 13

Describe assessment of iron stores

Answer 13

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)

Question 14

Describe stages of iron deficiency stages

Answer 14

Iron deficiency stages

1. Iron store depletion: ferritin below reference range but iron and Hgb normal
2. Iron deficient erythropoeisis: iron falls, TIBC rises, and decrease in % saturation, minimal anemia
3. Iron deficiency anemia: low iron, increased IBC, low % saturation, low ferritin (often less than 10-12 mg/L) and low Hgb

Question 15

Absent iron deficiency anemia is ___

Answer 15

Absent iron deficiency anemia is absent or reduced storage iron in reservoir (bone marrow, liver, spleen)

Question 16

Functional iron deficiency anemia is ___

Answer 16

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

Question 17

Inhibiting hepcidin ___

Answer 17

Inhibiting hepcidin maximizes iron availability

Question 18

Iron deficiency anemia can result from ____ or ____

Answer 18

Iron deficiency anemia can result from increased requirements or decreased iron supply

Question 19

Describe symptoms of iron deficiency anemia

Answer 19

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

Question 20

Treatment of iron deficiency anemia involves ____, ____, and ____

Answer 20

Treatment of iron deficiency anemia involves treating underlying cause of present, iron supplementation (every other day), and blood transfusion in symptomatic anemia

Question 21

Anemia of chronic disease is a ___ term

Answer 21

Anemia of chronic disease is a broad term

Question 23

Inflammatory stress ___ hepcidin and leads to ___

Answer 23

Inflammatory stress upregulates hepcidin and limits iron availability

Question 24

Describe pathogenesis of anemia of inflammation

Answer 24

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

Question 25

Describe symptoms of anemia of inflammation

Answer 25

Anemia of inflammation

• Symptoms from anemia: fatigue, difficulty breathing, dizziness, and lightheadedness
• Symptoms from an underlying disease process: inflammatory disease (RA), infection (osteomyelitis), cancer

Question 26

Describe typical lab findings of anemia of inflammation

Answer 26

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

Question 27

In anemia of inflammation, ferritin is ____ and Epo level is ____

Answer 27

In anemia of inflammation, ferritin is increased and Epo level is not appropriately increased

Question 28

In iron deficiency anemia, ferritin is ____ and Epo level is ____

Answer 28

In iron deficiency anemia, ferritin is reduced and Epo level is high

Question 29

Anemia of inflammation and iron deficiency anemia can ___

Answer 29

Anemia of inflammation and iron deficiency anemia can coexist

Question 30

Correction of underlying disease can ___ anemia of inflammation

Answer 30

Correction of underlying disease can improve anemia of inflammation

Question 31

___ should be used to treat concurrent iron deficiency

Answer 31

IV iron should be used to treat concurrent iron deficiency

Question 32

Hemochromatosis is ___

Answer 32

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

Question 33

Describe decreased hepcidin production

Answer 33

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

Question 34

Mutation / increased erythroid drive ___ hepcidin, leading to ___

Answer 34

Mutation / increased erythroid drive inhibits hepcidin, leading to excess iron availability

Question 35

Describe iron studies for hemochromatosis

Answer 35

Hemochromatosis iron studies

Question 36

Describe symptoms of hemochromatosis

Answer 36

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

Question 37

Hemochromatosis treatment involves ____, ____, and ____

Answer 37

Hemochromatosis treatment involves phlebotomy, iron chelation, and moderation of alcohol intake

Question 38

Describe therapeutic uses of hepcidin

Answer 38

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