Lecture 17 Disorders of Iron Heme Metabolism

Question 1

Anemia Classifications

Answer 1

1. Microcytic (usually hypochromic
2. Normocytic (usually normochromic)
3. Macrocytic (usually normochromic)

Question 2

Microcytic Anemias

Answer 2

• sideroblastic anemias
• iron deficiency
• anemia, chronic inflammation
• globin deficiency (thalassemia)

Question 3

Iron Deficiency Anemia (IDA)

Answer 3

Etiology (cause):

• inadequate intake (not enough to meet demand)
• increased need: infants, children, teens, pregnant/lactating women
• impaired absorption: ex. celiac disease, decreased stomach acidity
• chronic loss: ex. slow hemorrhage, hemolysis, menstruation

Question 4

The three iron compartments

Answer 4

• storage (ferritin in blood, BM, macrophages, liver cells)
• transport (serum transferrin)
• functional (Hgb, myoglobin, cytochromes)

Question 5

Stage 1 IDA

Answer 5

• progressive loss of stored iron
• iron reserve sufficient to supply transport and functional compartments
• RBC development still normal
• no signs of IDA on PBS; no symptoms
• serum ferritin would be decreased, BM iron would also be decreased

Question 6

Stage 2 IDA

Answer 6

• defined by storage
• RBC production normal (transport iron being used)
• Hgb drops but still could be in ref. range (still subclinical)
• ferritin decreased, serum iron decreased, TIBC increased
• RDW may start to increase
• FEP increased
• Transferrin receptors on cells increased
• no iron stores in BM when stained with Perl’s Prussian Blue

Question 7

Stage 3 IDA

Answer 7

• “Frank anemia”
• Hgb and Hct decreased
• storage iron depleted
• transport iron decreased
• abnormal RBC development
• microcytosis/normochromic -> microcytic/hypochromic
• ferritin markedly decreased
• FEP, transferrin receptors all increased

Question 8

Physical symptoms of Stage 3 IDA

Answer 8

• fatigue
• weakness especially with exertion
• pallor
• pica
• etc.

Question 9

Anemia of Chronic Inflammation (ACI)

Answer 9

• etiology: underlying condition: arthritis, TB, HIV, malignancies etc.
• pathophysiology: impaired ferrokinetics
• hepcidin is an acute phase reactant
• hepcidin destoys ferritin
• iron gets trapped in macrophages and hepatocytes
• when neutrophil die off, granules release lactoferrin -> lactoferrin binds iron (prevents bacteria from using iron)
• ferritin (acute phase reactant) binds some iron and contribute to ACID as RBCs have no ferritin receptor
• in BM: release of iron from macrophages is impaired by hepcidin and RBCs are deprived of iron and can’t develop

Question 10

ACID Laboratory Diagnosis

Answer 10

• mild anemia (90-110 g/L)
• no reticulocytosis (b/c erythropoiesis disrupted)
• leukocytosis/thrombocytosis
• may appear normocytic/normochromic in early stages of disease
• may co-exist with IDA
• iron studies:
  
  • low serum iron
  • low TIBC
  • transferrin saturation normal or low
  • serum ferritin is usually elevated due to inflammatory state
  • FEP elevated

Question 11

Treatment of ACID

Answer 11

• erythropoietin concurrently with iron

- inflammation - treatment/control of underlying condition

Question 12

Sideroblastic Anemias

Answer 12

Pathophysiology
- inadequate heme production
- BM iron abundant 
- iron awaiting incorporation into heme
- hallmark is ringed sideroblasts
Disorders
- Hereditary: 
   - X-linked
   - Autosomal
- Acquired:
   - Primary sideroblastic anemia (refractory)
   - Secondary sideroblastic caused by drugs and BM toxins

Question 13

Lead Poisoning

Answer 13

• acquired sideroblastic anemia/ porphyria
• interferes with porphyrin synthesis
• usually normocytic/normochromic
• repeated/prolonged exposure -> micro/hypo
• retic count high
• basophilic stippling (also present in thalassemias)
  Treatment
• remove source
• chelation EDTA therapy

Question 14

Iron Studies in Sideroblastic Anemia

Answer 14

• increase in serum iron and ferritin

- increase in BM iron with the exclusive presence of ringed sideroblasts

Question 15

Iron Overload

Answer 15

• Primary: genetic defect ex. hereditary hemochromatosis

- Secondary: Blood transfusions

Question 16

Iron Overload Pathogenesis

Answer 16

• overload -> free iron circulates
• accumulates in cells -> membrane damage and cell death
• liver: cirrhosis -> cancer
• skin: gold color
• pancreas -> diabetes (bronzed diabetes)
• heart -> CHF
• vit C and alcohol can worsen it

Question 17

Hereditary Hemochromatosis

Answer 17

• mutated proteins impair hepcidin regulation of ferroportin

- intestinal enterocytes continuously absorbs iron even when stores are normal

Question 18

Iron Overload (secondary)

Answer 18

• repeated transfusions
• iron present in transfused cells
• exceeds 1mg/day added by diet
• called transfusion-related hemosiderosis

Question 19

Fe Overload Lab Diagnosis and Treatment

Answer 19

• screening: increased transferrin saturation
• diagnostic procedures: incidental liver function test, iron studies, liver biopsy
• monitor: ferritin levels, Hgb, Hct
  Treatment:
• Hereditary hemochromatosis: lifetime therapeutic phlebotomy
• Transfusion-induced:
  
  • iron chelation