Heme #6: Disorders Of Iron Metabolism

Front 1

What constitutes the functional compartment of iron?

What constitutes the storage compartment of iron?

Back 1

Functional = Fe in Hb, myoglobin, and enzymes (catalase, cytochromes)

Storage= Fe in Hemosiderin and ferratin

Front 2

Hemosiderin vs. Ferratin

Back 2

Hemosiderin= Insoluble, found in tissue, stains with Prussian blue. Found in phagocytic cells.

Ferratin= water soluble, found in all tissues & in phagocytic cells. Doesn't stain with Prussian blue.

Front 3

In what form is iron circulated in the plasma? Where is iron absorbed from? What happens to excess iron?

Back 3

Transferrin= molecule that binds iron, carries it around

Absorbed from mucosal cells of duodenum into BM or Liver. No system for elimination of unwanted iron (deposits instead in organs).

Front 4

Who is more affected by Fe-deficiency anemia, M or F?

Dietary iron can present in what two forms? Which form absorbs best?

Back 4

Females- menstruation and loss of RBCs and iron.

Dietary iron = heme form (absorbed best, digested to iron) and non-heme form.

Front 5

Describe how iron is absorbed into the plasma (include the oxidation state of iron and specific proteins and transports)?

Back 5

Fe is absorbed as Fe2+ (ferrous) taken up by DMT-1 transporter in apical membrane of duodenal enterocyte.

It then gets oxidized to ferric form and transported by ferroportin in basolateral surface to the plasma (onto transferrin).

Front 6

Ferroportin vs. Hepcidin

Back 6

They are antagonists of one another

Ferroportin= transports iron out of cell and onto transferrin. Facilitates release of Fe from macrophages.

Hepcidin= inhibits ferroportin. Blocks release from macrophage. Blocks Fe absorption from GI.

Front 7

Iron deficiency anemia in men and non-menstruating women should trigger what important testing?

What age groups are particularly susceptible to Fe-deficiency?

Back 7

Evaluate for GI bleed (rule out cancer!) --> colonoscopy and gastroscopy

Infants, pregnant women, and adolescents (↑ growth). Also elderly tend to have deficiency. *and people of all age in underdeveloped countries.

Front 8

Signs/Sxs of Fe-deficiency anemia?

Back 8

Asymptomatic (!!)
Signs of anemia (weakness, pallor, palpitations, SOB, headache)
Pagophagia (pica), koilonychia (scooping), glossitis, angular stomatisi, web (Plummer-Vinson)

Front 9

What is Plummer-Vinson syndrome (aka Paterson-Kelly)?

Back 9

Dysphagia-web-anima

Dysphagia from post-cricoid web, Fe-deficiency anemia, and atrophic glossitis (triad)

Front 10

High or low serum transferrin in Fe-deficiency anemia? in Anemia of chronic disease?

High or low serum ferratin in Fe-deficiency anemia? in Anemia of chronic disease?

Back 10

Transferrin= HIGH in Fe-deficiency, LOW in ACD

Ferratin= LOW in Fe-deficiency (low stores), HIGH in ACD

Front 11

What hematological changes are seen in Fe-deficiency anemia?

What happens to the Retic count?

Back 11

Microcytic, Hypochromic cells, Anisocytosis (variation in size), and Poikilocytosis (variation in shape)

Target cells, Pencil cells might be seen as well. SUBOPTIMAL retic count (don't have necessary Fe in order to be healthy)

Front 12

What is seen on this bone marrow biopsy (it is stained with Prussian Blue)?

Back 12

Iron deficiency (no staining of hemosiderin in macrophages).

Front 13

What lab values (serum iron, transferrin, Hb, and ferratin) would you expect in

Fe deficiency without anemia
Fe deficiency with anemia
Severe Fe deficiency with severe anemia

Back 13

Fe deficiency without anemia: low serum iron, low ferratin, normal Hb, normal transferratin

Fe deficiency with anemia: low iron, low ferratin, elevated transferratin, Hb is low 9-12

Fe deficiency with SEVERE anemia: low iron, low ferratin, HIGH transferratin, Hb is super low 6-7

Front 14

What is the pathophysiology of anemia that occurs in patients with malignancies or chronic infections?

Why is there low transferrin with this syndrome?

Back 14

Anemia of Chronic disease: Inflammation --> IL-6 release from macrophages --> stimulates liver to ↑ Hepcidin production--> blocks Ferroportin (thus Fe-absorption and release from macrophages).

The body does not perceive a state od iron loss since theres so much iron in store, and ferratin is so high. thus, transferrin levels are low.

Front 15

What is the problem in Juvenile Hemochromatosis?

Back 15

Absence of HJV (hemojuvelin)- a protein in the liver which makes hepcidin. Decreased hepcidin means unopposed ferroportin and increased Fe absorption (and deposition)

Front 16

Fe-deficiency anemia or Anemia of Chronic disease? How can you tell?

Back 16

ACD (because there's BM hemosiderin and iron within macrophages but not in RBCs).

In Fe-deficiency, Iron is absent from both macrophages and RBC precursors.

Front 17

Treatment of Fe-deficiency anemia?

Treatment of Anemia of Chronic Disease?

Back 17

Fe-deficiency: Treat underlying cause if there is one. Fe supplementation (usually oral), otherwise parenteral for acute situations or if EPO is given in CRF patients.

ACD- Treat underlying condition. Could transfuse with RBC. Giving EPO sometimes helps.

Front 18

What genetic disorder leads to increased absorption of iron from the duodenum?

What acquired situations cause increased iron deposition/ damage in the body?

Back 18

Hereditary Hemochromatosis

Repeated blood transfusions (ex: thalassemia minor, aplastic anemia, etc.)

Front 19

What is the primary gene defect in Hereditary hemochromatosis?

Describe the 2 models.

Back 19

HEF gene defect (C282Y gene mutation). HFE = detects body Fe and regulates DMT accordingly.

1. Crypt= HFE is impaired, so cell perceives it as deficient state and ↑ DMT. ↑ Iron extraction from GI.

2. Liver model= HFE is impaired so it blocks Hepcidin production. It causes unopposed Ferroportin (which transports Fe into circulation leading to overload).

Front 20

Sxs of Hemochromatosis?

Treatment? Why do you have to be careful when giving repeated blood transfusions to patients with Hemochromatosis?

Back 20

Sxs= Fe deposits in organs and tissues, thus-
Liver abnormalities, weakness, lethargy
Skin hyperpigmentation

Treat with PHLEBOTOMY. Repeated blood transfusion to patient can cause further Fe overload --> give Iron chelator to offset this.