Iron/Heme Metabolism - Goueli

Question 1

When prescribing Isoniazid to a patient, what should you be cautious of?

Answer 1

• Vitamin B6 deficiency
  
  • results i peripheral neuropathy
  • CNS effects
  • anemia (microcytic, hypochromic)
• Supplement with Vitamin B6 to prevent this!

Question 2

Why does Vitamin B6 Deficiency commonly result in anemia?

Answer 2

• Vitamin B6 (pyridoxine) is required in the rate limiting step of heme synthesis
  
  • pyridoxal phosphate is a necessary cofactor for Delta-ALA synthase
  • slowed heme production without VitB6

Question 3

Heme is degraded to for what?

Answer 3

bilirubin

Question 4

Bilirubin is conjugated with glucuronic acid in what organ?

Answer 4

liver

Question 5

If levels of indirect unconjugated bilirubin are high, what should you be concerned for?

Answer 5

Extravascular or Intravascular Hemolysis in the blood

(takes place before it reaches the liver)

Question 6

If levels of direct conjugated bilirubin are elevated, what should you be concerned about?

Answer 6

Liver, Biliary, or Intestinal obstruction

(blockage in the liver and beyond)

Question 7

Greater than 50% of patients with sporadic Porphyria Cutanea Tarda (deficiency of hepatic uroporphyrinogen decarboxylase or URO-D) also test positive for what hepatic condition?

Answer 7

Hepatitis C (HCV positive)

Question 8

In a 60 yoa male patient with diagnosed iron deficiency anemia of unknown cause, what should your first move in management/treatment be?

Answer 8

Look for GI Bleed with Colonoscopy!

• find source of blood loss first
  
  • rule out malignancy:
    
    • gastrointestinal, genitourinary, colorectal, gastric, endometrial, cervical, bladder
• then rule out malabsorption
  
  • celiac disease
  • H-pyloria
• rule out intravascular hemolysis
• finally, supplement/fortify diet with iron

Question 9

What causes Anemia of Chronic Disease (AOCD)?

Answer 9

• Inflammation (IL-6/IL-1) increases hepatic transcription, expression, synthesis of hepcidin
  
  • increased hepcidin stops iron from leaving cells
    
    • destroys ferroportin (only known exporter of iron)
  • iron stores increased, but decreaded iron utilization (unavailable)
  • not enough iron available to keep up with demands of erythroid proliferation
  • results in hypoproliferative anemia

Question 10

What is the difference between Ferritin vs. Transferrin in iron metabolism?

Answer 10

• Ferritin
  
  • iron storage in cytosol
  • high synthesis in high iron states
• Transferrin
  
  • plasma iron transporter
  • delivers iron released by macrophages and enterocytes to bone marrow
  • high synthesis in low iron states

Question 11

What will iron panel tests show in Iron Deficiency Anemia?

(Serum Iron, Serum Ferritin, Transferrin iron saturation, Total Iron Binding Capacity, Transferrin, Hemoglobin)

Answer 11

• Serum Iron: Low
• *Serum Ferritin: LOW
• Transferrin iron saturation %: Low
• Total Iron Binding Capacity: High
• Transferrin: High
• Hemoglobin: LOW

Question 12

What will iron panel tests show in Anemia of Chronic Disease?

(Serum Iron, Serum Ferritin, Transferrin iron saturation, Total Iron Binding Capacity, Transferrin, Hemoglobin)

Answer 12

• Serum Iron: Low
• Serum Ferritin: High
• *Transferrin iron saturation %: LOW
• Total Iron Binding Capacity: Low
• Transferrin: Low
• Hemoglobin: Low

Question 13

What will iron panel tests show in Hemachromatosis?

(Serum Iron, Serum Ferritin, Transferrin iron saturation, Total Iron Binding Capacity, Transferrin, Hemoglobin)

Answer 13

• Serum Iron: High
• Serum Ferritin: High
• *Transferrin iron saturation %: HIGH (>45%)
• Total Iron Binding Capacity: Low
• Transferrin: Low
• Hemoglobin: Normal

Question 14

How do HFE gene mutations cause iron overload in Type 1 Hereditary Hemachromatosis?

Answer 14

• HFE = transmembrane protein belonging to MHC Class I, expressed highly in the liver
  
  • Helps regulate hepcidin expression (w/ TfR1/TfR2)
• HFE Mutation: usually cysteine → tyrosine substitution at amino acid 282 (C282Y)
  
  • results in lack of interaction of HFE w/ TfR2 and reduced cell surface expression
    
    • decreased hepcidin expression (no regulator of iron absorption)
    • increased Fe absorption
    • decreased storage of iron in macrophages

Question 15

What are the two forms of dietary iron?

Answer 15

• Heme iron
  
  • hemoglobin and myoglobin in beef, chicken, fish, etc.
• Non-heme iron (Fe³⁺)
  
  • cereal, vegetables, fortified flour

Question 16

Which form of dietary iron is best absorbed? Why?

Answer 16

• Heme iron best absorbed
  
  • hemoglobin/myoglobin in beef, chicken, fish, etc.
• Iron absorption is enhanced by gastric acid in the proximal small bowel (duodenum)
  
  • Fe²⁺ valence absorption = better
  • Heme iron is in ferrous form (Fe²⁺)
  • Non-heme iron is usually present in the ferric form (Fe3+)
  • Heme Fe > Non-Heme Fe