Iron disorders and megaloblastic anemia

Iron
1. Can be divided into:
  1. Storage iron
    1. Ferritin, mainly in reticuloendothelial system, macrophages and liver
  2. Functional iron
  3. Transport iron
    1. Transferrin
2. Only mechanism of elimination is through desquamation
  1. 1-2 mg/die lost
3. Normal amount is 4g (2g in the liver)
  1. Severe consequences when there are >7g in the body
Hepcidin
1. Regulates the amount of iron absorbed by the intestine
2. Secretion is tightly regulated both by iron levels and by inflammation
3. Released by liver cells whenever there is an increase in the levels of Fe
4. It binds to ferroportin
  1. Molecule expressed on macrophages and duodenal cells
Iron deficiency anemia
1. Iron deficiency affects 1/3 of the total population
2. Causes
  1. Increased requests
    1. Infants
    2. Women during pregnancy
  2. Inadequate intake
    1. Extreme poverty
    2. Vegetarians
  3. Absorption defects
    1. Gastrectomy
    2. IBD, celiac disease
    3. Intestinal infections that cause diarrhea
  4. Chronic blood losses
    1. Polyps
    2. Hemorrhoids
    3. Cancer
    4. Chronic intake of NSAIDs
    5. Menorrhagia in women
    6. Chronic blood donations
3. Iron parameters
  1. Serum iron
  2. Transferrin
  3. Serum ferritin
4. Stages
  1. Stage 1 - Iron deficiency
  2. Stage 2 - Iron deficient erythropoiesis
  3. Stage 3 - Iron deficiency anemia (IDA)
    1. Transferrin is high
5. Clinical features
  1. Anemia-related symptoms
  2. Iron deficiency in other cells
  3. CNS symptoms
    1. Pica syndrome
6. Peripheral blood smear
  1. Microcytic hypochromic anemia
  2. In some cases altered morphology (elliptocyte or teardrop)
7. Diagnosis
  1. Measure iron levels, Hb levels and look at peripheral smear
8. Treatment
  1. Main goals
    1. Repair Hb deficiency and replenish Fe stores
      1. Best is ferrous sulphate
        If it is contraindicated, parenteral iron is administered
    2. Eliminate underlying casues
9. Most common type worldwide
Megaloblastic anemias
1. Vitamin B12 (cobalamin)
  1. Causes of vitamin B12 deficiency
    1. Inadequate diet
      1. Vegetarians
    2. Malabsorption
      1. Pernicious anemia
        Lack of IF that affects mainly elderly people
        Most commonly present with other autoimmune diseases
        Autoantibodies against parietal cells found in 90% of cases, but rather unspecific
        Main problem is the increased risk of developing polyps and gastric tumors due to chronic gastric atrophy
      2. Gastric atrophy and gastrectomy
    3. Terminal ileum diseases
      1. Infections (tropical sprue)
      2. IBD
      3. TBC
      4. Local surgery
    4. Competition
      1. Diphyllobotrium latum
  2. Pathways in which B12 is involved
    1. Thymidylate synthesis (for DNA)
    2. Myelin lipid synthesis
  3. Clinical findings
    1. Chronic anemia
    2. Megaloblastc bone marrow
    3. Epithelium (glossitis and cheilitis)
    4. CNS
  4. Bound to intrinsic factor in the GI tract
  5. Transported in the circulation bound to transcobalamin II
  6. Cobalamin deficiency requires 4-5 years to develop
2. Folate deficiency
  1. Clinical findings
    1. As vitamin B12 deficiency (but CNS symptoms are not present)
  2. It requires 2-3 months to develop
  3. Causes
    1. Inadequate diet
      1. Teenagers and elderly
      2. Heavy drinkers
    2. Increased needs
      1. Pregnancy
      2. Chronic hemolysis
    3. Malabsorption
      1. IBD
      2. Tropical sprue
      3. Ethanol
    4. Drugs
      1. Methotrexate and 5FU
      2. Hydroxyurea and trimethoprim
3. Lab tests
4. Therapy
  1. Do no transfuse patients
    1. Only exceptions are old patients with cardiac symptoms
  2. Combination of both vitamin B12 and folate is administered
    1. This also prevents the folate trap
5. High indirect bilirubin contents
6. High LDH levels
Anemia of chronic inflammation
1. Normochromic and normocytic
2. Main causes
  1. Inflammation
  2. Autoimmune diseases (RA)
  3. Infections (TBC)
  4. Cancer
3. Stimulated by release of inflammatory cytokines
  1. IL1
  2. IL6
  3. TNF-α
4. Require iron IV as replacement therapy, but whenever the underlying cause is an infection this is contraindicated
5. Another possible treatment is administration of EPO
6. Iron abnormalities are due to:
  1. Reduced release of iron from macrophages
  2. Reduced intestinal iron absorption
  3. Iron refractoriness
Iron overload
1. Genetic/Primary
  1. Hereditary hemochromatosis
    1. Clinical complications
      1. Liver (75%)
      2. Heart (20%)
      3. Pancreas (40%)
      4. Pituitary (40%)
      5. Endocrine glands
      6. Joints
      7. Skin
        Hyperpigmentation
    2. Diagnosis
      1. Evaluate level of saturation of transferrin
      2. MRI can be used to evaluate the condition of the liver
    3. Treatment
      1. Phlebotomy
        It cannot be done in anemic patients
        Iron chelators
    4. AR disorder
    5. Late onset and higher prevalence in males
    6. Liver is the first organ in which there is increased iron storage
    7. Due to deficiency in Hepcidn, due to mutations in HFE gene
2. Secondary/Acquired
  1. Chronic blood transfusions
  2. Iron loading anemias

Next up

Iron disorders and megaloblastic anemia

Description

Resource summary

Media attachments

Similar

	Created by LewisLewis over 10 years ago