249. Iron and Anemia of Chronic Disease

Question 1

How is Iron Absorbed into the body?

What regulates body iron level? What factors modulate this molecule?

What transports iron in blood? What stores iron?

What are the 4 tests of iron levels in body?

Answer 1

Absorption: Fe3+ to Fe2+ by gastric acid, Fe2+ binds DMT1 transporter into duodenal enterocyte, enters blood through ferroportin, where it binds transferrin

Hepcidin

• fx: inhibit Fe absorption
• suppressed by serum protease TMPRSS6, or any increased drive for erythroid activity (Erythroferrone)
• stimulated by BMP6/SMAD, inflammation (IL-6 through JAKSTAT)

Transferrin: transports iron, increase levels in iron deficiency

Ferritin: stores iron in cells, decrease levels in iron deficiency, upregulated in inflammation

1. Serum Iron (iron bound to transferrin)
2. Total Iron Binding Capacity (measure of transferrin)
3. % Saturation: % of Iron/TIBC
4. Ferritin: measure of total body iron stores

Question 2

Iron Deficiency Anemia

• epidemiology
• causes
• two precursor stages
• labs, hepcidin levels
• peripheral blood smear and CBC abnormalities
• tx

Answer 2

Epi: most common anemia worldwide
Causes: blood loss, malabsorption, poor diet, hookworms, growth/pregnancy
Precursor: 1. Iron Store Depletion: ferritin below normal; 2. Iron-Deficient Erythropoiesis: serum iron low, TIBC rises, low % sat, low ferritin, minimal anemia and little change to MCV (slight normocytic anemia)

Labs

• low serum iron, high TIBC, low % sat, low ferritin
• suppressed hepcidin (appropriate)
• microcytosis, hypochromia, high RDW (some microcytic, some normal, some pencil/cigar shaped)

Tx:

• Iron supplementation (oral if functional absorption, IV otherwise), iron absorption best with low, less frequent doses (prevent high hepcidin)
• Transfusion in acute settings

Question 3

Anemia of Inflammation (chronic disease)

• epidemiology
• labs, hepcidin
• causes/assoc diseases
• blood smear
• special test to ddx from IDA
• tx

Answer 3

Epi: most common anemia in hospitalized patients

Labs:

• low serum iron, low TIBC, high ferritin, low % sat
• soluble transferrin receptor assay (sTfR): use to determine if IDA or AI predominates in mixed CP, IDA has high sTfR (upregulated with high transferrin), AI has low sTfR
• typically normochromic, normocytic; microcytosis in severe longstanding cases

Cause:
Inflammation = IL-6 = stim production of hepcidin = unable to increase available Fe 
- inflammatory conditions 
- infection
- malignancy

Tx:

• treat underlying disease!
• complementary strategies: oral iron supplement (only for concurrent IDA, will not be able to increase free Fe in pure AI), IV iron (bypass hepcidin)

Question 4

Hemochromatosis

• what is it
• epidemiology
• genetics and other causes
• dx
• sx/CP
• tx

Answer 4

Excess iron loading of tissues

• prevalence high in N EU ancestry
• primary: mutations in genes of iron transport (HFE = produces hepcidin, HJV, transferrin receptor 2, ferroportin1) - note that not everyone with genotype has phenotype
• secondary: transfusion-assoc (high iron influx from blood products)

Dx:

• high serum Fe, high % sat, high ferritin, low TIBC
• liver biopsy (increased Fe deposition), MRI to assess iron deposition in end organs (liver, heart)

Sx/CP

• chronic fatigue
• liver: abnormal LFTs, cirrhosis, risk HCC
• DM (pancreas damage)
• Hypogonadism (gonad damage)
• arthritis of MCPs
• cardiomyopathy/arrhythmia
• bronzing of skin
• more susceptibility to some infections (Listeria, Yersinia, Vibrio) - grow better in high iron

Tx:

• Mainstay: Phlebotomy (blood letting) to reverse some organ damage (but cirrhosis, DM, gonadal failure, joint destruction not reversible)
• Iron Chelation Therapy: SC, IV, oral options for pts where phlebotomy not an option
• moderate alcohol intake (prevent more liver damage)