Red Cell Disorders II

Question 1

Explain iron metabolism in the body.

Answer 1

• Daily intake – 10-20 mg, poorly absorbed in duodenum (10- 15%)
• Daily loss – 1-2 mg
• Total body iron – 6 g (♂); 2.5 g (♀)
• Functional – Hgb, myoglobin, enzymes
• Storage – ferritin, hemosiderin
• There is constant recycling
  Hepcidin inhibits iron uptake from enterocytes to serum
• Inappropriately low in hereditary hemochromatosis
• Inappropriately high in anemia of chronic disease

Question 2

Explain iron deficiency anemia.

Answer 2

Clinical features	
* Pallor, fatigue, weakness	
* Pica	
* Atrophic glossitis, angular stomatitis, koilonychia	
Plummer-Vinson syndrome (Paterson-Brown-Kelly syndrome) that consist of			
* Iron deficiency anemia		
* Atrophic glossitis		
* Esophageal webs		
Pathology	
* Hypochromic, microcytic anemia	
* Anisocytosis	
* No increase in reticulocytes	
* Decreased serum iron	
* Decreased ferritin	
* Increased transferrin and soluble transferrin receptor	
* Absent storage iron in bone marrow

Question 3

Explain anemia of chronic disease.

Answer 3

• InfammationŽ -> increase in hepcidin due to inflammatory mediators such as IL-6(released by liver, binds ferroportin on intestinal mucosal cells and macrophages, thus inhibiting iron transport) ->decreasesŽ release of iron from macrophages and iron absorption from gut.
• Associated with conditions such as rheumatoid arthritis, SLE, neoplastic disorders, and chronic kidney disease.
• Decreased iron, decreased TIBC, increased ferritin.
• Normocytic, but can become microcytic.
• Treatment: EPO (chronic kidney disease only).

Question 4

What is the principle etiology behind megaloblastic anemia?What are its associated findings?

Answer 4

• Its associated findings are hypersegmented neutrophils and macrocytic RBCs
• Folate is required for DNA synthesis to transfer one carbon groups for purine synthesis, impaired DNA synthesis leads to delayed Žmaturation of nucleiof precursor cells in bone marrow relative to maturation of cytoplasm.

Question 5

Explain how does folate deficiency leads to megaloblastic anemia and what are its associated findings?

Answer 5

Folate deficiency:
* Causes includemalnutrition (eg, alcoholics), malabsorption, drugs (eg, methotrexate, trimethoprim, phenytoin), increased requirement (eg, hemolytic anemia, pregnancy). Increased homocysteine, normal methylmalonic acid. No neurologic symptoms (vs B12 deficiency).

Question 6

Explain how does B12 deficiency leads to megaloblastic anemia and what are its associated findings?

Answer 6

Vitamin B12 deficiency (Cobalamin):Causes: insuficient intake (eg, veganism), malabsorption (eg, Crohn disease), pernicious anemia, Diphyllobothrium latum (fish tapeworm), gastrectomy.Findings:
* Increased homocysteine, increased methylmalonic acid.
Neurologic symptoms: subacute combined degeneration (due to involvement of B12 in fatty acid pathways and myelin synthesis, deficiency leads to demyelination): spinocerebellar tract, lateral corticospinal tract, dorsal column dysfunction. Historically diagnosed with the Schilling test, a 4-stage test that determines if the cause is dietary insufficiency vs malabsorption.

Question 7

How is vitamin B12 absorbed in the gut.

Answer 7

• Hepatocorrin is released in the saliva which binds to vitamin B12 initially.
• Intrinsic factor is released in the stomach by parietal cells, B12 dissociates from heptocorrin in the duodenum in the presence of proteases and eventially binds to intrinsic factor.
• B12 bound to intrinsic factor is eventually absorbed in the gut by ileal cells.

Question 8

Explain pernicious anemia.

Answer 8

Chronic atrophic gastritis due to autoantibodies against parietal cells. This leads to megaloblastic anemia.

Question 9

What changes do we see in the CNS in vitamin B12 deficiency.

Answer 9

Periventricular white matter degeneration in the brain and posterior column degeneration in the spinal cord

Question 10

What are the findings on peripheral blood smear and in bone marrow of megaloblastic anemia?

Question 11

What are the changes observed in anemia of blood loss?

Answer 11

• Acute blood loss
• Hypovolemic shock
• No immediate change in hemoglobin level
• Slow fluid shift from interstitial space to intravascular space leads to low hemoglobin
• Normochromic, normocytic anemia
• Reactive leukocytosis and thrombocytosis may occur