43. Anemias due to disturbed hemopoiesis. Anemias due to increased hemolysis.

Anemias due to disturbed hematopoiesis. Anemias due to increased hemolysis

Disturbed hematopoiesis

• Anemia resulting from decreased production of erythrocytes by the bone marrow
• To produce RBCs we need the following:
• Iron
• Vitamin B12
• Folic acid
• Bone marrow
• Erythropoietin

1) Iron-deficient anemia

• Most common anemia
• Causes:
• Chronic hemorrhages (e.g. GI bleeding)
• Increased physiological requirements (e.g. child’s growth)
• Decreased Fe-uptake
• Altered Fe-transformation (e.g. achlorhydria = absence of HCl in gastric juice which is needed to convert Fe³⁺ to Fe²⁺ to be absorbed)
• Decreased Fe-absorption
• Improper Fe-transport to hematopoietic organs
• RBCs are microcytic, hypochromic, poikilocytosis (irregular shape), and anisocytosis (irregular size)
• RBC count may be normal
• Pathogenetic stages:

1. Pre-latent Fe-deficit - ↓ ferritin, ↓ intestinal absorption
2. Latent Fe-deficit - ↓ serum Fe, ↓ ferritin, ↑ total iron binding capability (TIBC)
3. Manifest Fe-deficiency anemia - ↓ RBC, ↓ Hb, ↓ Hct ↓ MCV ↓ MCHC

• Manifestations = fatigue, palpitations, dyspnea, angina, tachycardia, brittle hair, pica

2) Megaloblastic anemias

• Caused by abnormal nucleic acid synthesis that results in enlarged red cells (MCV > 100 fL) and deficient nuclear maturation
• Cobalamin (vitamin B12) and folic acid (vitamin B9) deficiencies are the most common cause of megaloblastic anemias
• Because megaloblastic anemias develop slowly = few symptoms until advanced stage
• Erythrocyte profile in megaloblastic anemia:
• Anisocytosis
• Poikilocytosis
• Macrocytes
• Ovalocytes
• Howell-Jolly bodies
• Syndromes for megaloblastic anemias:

1. Anemic syndrome - anisocytosis, poikilocytosis, Howell-Jolly, MCV > 100 fl
2. GIS - achylia gastrica, stomach ache, diarrhea, vomiting, hunter glottis
3. Neurological syndrome - funicular myelosis, dementia

a) Cobalamin deficiency anemia

• Vitamin B12 is essential for DNA synthesis → deficiency results in altered DNA synthesis → failure of cell division of RBCs
• There is normal Hb production but too little RBCs → macrocytic and hyperchromic
• It is found in all foods of animal origin
• It is absorbed via binding to intrinsic factor (IF) - a protein secreted by the gastric parietal cells
• The complex travels to the ileum, where it binds to membrane receptors that transport B12 across the membrane → binds to transcobalamin II
• Any defects in this pathway = deficiency
• Causes:
• Pernicious anemia (Addison-Biermer disease) - auto Abs against parietal cells → damage to parietal cells → lack of IF so B12 can’t be absorbed
• Gastrectomy
• ↓ RBC, ↑ MCV, normal MCHC
• Signs and symptoms = hunter glossitis (smooth tongue), neurological changes caused by deranged methylation of myelin protein (symmetric paresthesias of the feet and fingers, loss of vibratory and position sense)

b) Folic acid-deficiency anemia