Hemolytic Anemias: Intracorpuscular Defects

• 1. Extravascular vs. intravascular sites
• 2. Extracorpuscular vs. intracorpuscular defects
• 3. Hereditary vs. acquired

RBC-->Heme, Globin

Heme-->Fe, Protoporphyrin-->CO

protoporphyrin-->unconjugated bilirubin-->liver-->conjugated bilirubin excreted__>urobilinogen and urobilin

• conjugated bilirubin excreted Kidney__>urobilinogen and bilirubin

• low RBC, haptoglobin
• high Hgb breakdown, bilirubin, urobilinogen in feces and hemoglobin in urine
• hemosiderin in kidney tubules

• erythroid hyperplasia
• NRBC, increased reticulocytes, howel-jolly bodies

• Hereditary spherocytosis
• Hereditary elliptocytosis
• hereditary stomatocytosis
• hereditary xerocytosis

• spectrin and ankyrin deficency
• conditioning of RBC by spleen

• hyperbilirubinemia
• reduced haptoglobin
• increase reticulocyte
• MCHC increased

It can be used to test the integrity of cellular membrane

• spectrin and/or protein deficiency or dysfunction?
• membrane is weakened in stress

• slight reticulocytosis
• decrease haptoglobin
• normal rbc indices

permeable membrane permits cation leaks into and out of RBC

• Increased MCV
• Decreased MCHC
• macrocytosis
• stomatocytes

• Sodium leaks into cell and K leaks out
• H₂O enters and RBC swell

H₂O exits the cell causing dehydration

• lack of an enzyme that converts NADP to NADH
• Only pentose phosphate pathway that reduces Glutathione

protects hemoglobin from oxidative denaturation

Methemoglobin reductase reduces methhbg to hgb using NADH 

• decreased Hgb
• hemoglobinuria
• elevated bilirubin
• decreased haptoglobin
• drug induced

• decrease ATP per cell
• leads to cell water loss and shrinkage (echinocytes)
• increased membrane rigidity

• cause increase levels of methemoglobin
• not an effective hemoglobin carrier
• may be drug induced