Anemia: Impaired RBC production

What are all the anemias that are produced by a lack of/impaired production of RBCs? (8 types, 2 of which have subtypes within them)

1. Iron Deficiency Anemia (IDA)

2. Anemia of chronic disease (ACD) → a.k.a Chronic inflammation anemia

3. Sideroblastic anemia

4. Porphyrias → 2 types

   1. Congential erythropoietic porphyria (CEP)

   2. erythropoietic protoporphyria (EPP)

5. Megaloblastic anemias → folic acid & vit. B deficiency

   1. Pernicious anemia (PA) → autoimmune vit.B deficiency

6. Aplastic anemia

7. Myelophthisic anemia

8. Anemia of Chronic Renal Disease → EPO is decreased

What is the most common anemia worldwide?

Iron deficiency anemia (IDA)

What is the etiology (cause) of Iron Deficiency Anemia (IDA)? List the 3 potential causes of this anemia.

Inadequate stores of iron for hemoglobin

1. Decreased intake of iron: due to diet (vegetarian), infancy, pregnancy

2. Increased need for iron: pregnancy & lactation, children & teens

3. Increased loss of iron: menstruation, chronic blood loss (slow bleed, GI tract bleed), intravascular hemolytic processes

What is the pathogenesis (development) of iron deficiency anemia? What are the 3 stages this deficiency has? List the parameters for each stage as well.

Develops slowly over time as iron components become depleted (3 stages)

Stage 1: Storage iron deficiency (Ferritin)

• serum ferritin is decreasing, no anemia will be detected (RBCs will appear normal) due to early stages (body still has enough iron in system)

  • Parameters: Hbg, serum iron, TIBC, and ferritin will be normal

Stage 2: Transport iron depletion (transferrin)

• Iron storage fully depleted, deficient erythropoiesis (production of RBCs).

• Not enough iron to bind protoporphyrin ring (which creates heme) → Zinc binds to ring in place of iron

  • Parameters: Hgb is normal, TIBC is high, serum iron & ferritin are low

    • TIBC is high b/c cells are trying to capture available iron

Stage 3: Functional iron depletion (full IDA)

• RBCs fail to develop normally (or at all), patients now get anemia symptoms

• Hgb & Hct are low → creates Microcytic & hypochromic cells

  • Parameters: TIBC is high, Hgb, serum iron, & Ferritin are low

What are the symptoms of those who have Iron deficiency anemia (IDA)?

• Pica syndrome: craving crushed ice, dirt/clay, starch

• Sore tongue (glossitis), cracks at mouth corners

• Koilonychia: spooning of fingernails

Who all is at risk (epidemiology) of iron deficiency anemia (IDA)?

Menstruating women, growing children (including infants), senior citizens (poor diet), and pregnant women

When checking for iron deficiency anemia (IDA), there are three different testing stages: Screening, Diagnostic, and specialized. Explain what test is performed within each category and what they detect. What decreased level indicated IDA?

Screening: Complete blood count (CBC)

• Detects hypochromic (large central pallor), microcytic anemia

  • decreased Hgb & elevated RDW

Diagnostic: iron studies

• Detects decreased ferritin, serum iron, & % saturation

  • ferritin is first detection of IDA

• Detects increased TIBC (increases b/c cells trying to capture iron)

Specialized: Zinc protoporphyrin (ZPP) & BM testing

• Zinc is incorporated into heme instead of iron ∴ [ZPP] ↑ in iron deficient erythropoiesis → ZPP serves no function to RBCs

• BM is stained w/ Prussian blue to check for absences of hemosiderin

  • Hemosiderin is iron storage in body (ferritin & hemosiderin found in liver, spleen, & BM)

When should diagnostic iron studies be done on a person and why?

Drawn either while a person is fasting or early in the morning

• b/c iron levels drop throughout the day & iron absorbed from a meal can falsely elevate results

What is the treatment given to those who have iron deficiency anemia (IDA)?

• Iron supplements: pills taken on empty stomach for best absorption (ferrous sulfate0

• If caused by injury: stop GI bleed, renal stones, etc.

What is the way RBCs classically look like when someone has iron deficiency anemia (IDA)? When do symptoms finally show up (what stage) and when does a CBC show abnormal results (what stage)?

• Microcytic, hypochromic

• Stage 3

What is the etiology (cause) of Anemia of chronic disease (ACD / chronic inflammation)?

Causes of ACD: chronic disease

• Rheumatoid arthritis

• Systemic lupus erythematosus (SLE)

• TB

• HIV

• chronic UTIs

What is the pathogenesis (development) of anemia of chronic disease (ACD)? What does sideropenia result in and what are the two causes of it (explain them)?

Abundant iron in storage BUT has sideropenia (low serum iron)

• Sideropenia results in decreased RBC production due to iron deficiency

Sideropenia causes:

1. Decreased EPO production: inflammatory cytokines (from macrophages) inhibit EPO → contributes to ACD

2. Increased hepcidin: Produced by hepatocytes to regulate body iron levels

• Released in response to inflammatory cytokines

• Blocks iron uptake in duodenum & release of iron from macrophages in spleen (recycling) → prevents iron delivery to developing RBCs

What will RBC look like in those who have anemia of chronic disease? Include the parameters. What two diagnostic tests can be performed to check for ACD?

• RBCs will be normochromic, normocytic (can be hypochromic, microcytic)

• Retics - normal or decreased amount in PB

  • Parameters: Hgb low (9-11 g/dL), RDW normal, Ferritin normal/slightly increased

    • Serum iron, TIBC, & % saturation decreased

Tests:

Iron studies & ZPP (which will be increased due to iron-deficient erythropoiesis)

What parameter differentiates anemia of chronic disease (ACD) from iron deficiency anemia (IDA)?

• Serum ferritin will show difference between ACD and IDA.

  • ACD will have normal/increased ferritin

  • IDA will have decreased ferritin

What is the treatment for those who have anemia of chronic disease (ACD)?

Anything that eliminates inflammation

• Therapeutic EPO (Epogen or Procrit)

What is therapeutic EPO made of? (What is it?) How was it made/discovered? What has it been used as outside of medical use?

• Synthetic erythropoietin

  • gene that makes EPO was cloned in ‘85 and is implanted in guinea pigs to make artificial EPO for treatment

Has been used as a doping drug b/c it increases RBC amount which increases amount of O2 being carried throughout body (improves endurance).

What is the most common anemia that occurs worldwide due to lack of/impaired production of RBCs?

What anemia is the most common amongst hospital patients (also due to impaired RBC production)?

• Common worldwide: iron deficiency anemia (IDA)

• Common hospital: Anemia of chronic disease (ACD)