5.5 Normocytic anemias with extravascular Hemolysis Flashcards
What, generally, is hereditary spherocytosis?
Mutation in the cytoskeletal components of RBCs, causing them to bulge into spheres d/t loss of membrane blebs
What are the cytoskeletal tethering proteins that are defective in hereditary spherocytosis? (3)
- Spectrin
- Ankyrin
- Band 3.1
What is the RDW with hereditary spherocytosis? Why?
Large, since there is a large variation between new and old RBCs
What causes the anemia with hereditary spherocytosis?
RBCs are consumed by the macrophages in the spleen
What happens to the MCHC with hereditary spherocytosis? Why?
Increases–Same amount of Hb in a smaller RBC
What are the clinical features of hereditary spherocytosis?
- Splenomegaly
- Jaundice with unconjugated bili
- Increased risk for bilirubin gallstones
There is an increased risk of aplastic crisis in patients with hereditary spherocytosis with what infectious disease? Why?
Parvovirus B19–infects the erythroid precursors
What causes the splenomegaly with hereditary spherocytosis?
Work hypertrophy
What is the classic test to diagnose hereditary spherocytosis? What is the basis for this?
Osmotic fragility test–Increased fragility in a hypotonic solution, since the loss of membrane that occurs with hereditary spherocytosis leaves no room for excess water to accumulate.
What is the treatment for hereditary spherocytosis?
Splenectomy
What are the classic peripheral blood smear findings with a splenectomy? What causes this?
Howell-Jolly bodies–lack of removal of DNA from RBCs due to a loss of splenic macrophages
What is the problem that occurs in sickle cell anemia? Inheritance pattern?
AR mutation in the beta globin chain, where a glutamic acid is replaced with a valine
What causes the RBCs to sickle with sickle cell anemia?
Hydrophobic valine patch causes RBCs to stick together to hide hydrophobic patch away from water in the serum
What is the supposed benefit of sickle cell anemia?
Protection against falciparum malaria
When does sickle cell disease result, as opposed to sickle cell trait?
Trait = one mutated beta globin gene
Disease = both beta globin genes are mutated
What are the components of HbS?
Alpha-2 beta (S) 2
HbS polymerize with under what conditions? (3)
- Deoxygenation
- Dehydration
- Acidosis
What is the role of HbF in sickle cell disease?
- Protective factor in the first few months of life
- Hydroxyurea increases levels of HbF
What is the role of hydroxyurea in the treatment of sickle cell anemia?
Increases levels of HbF
What is the problem that occurs with constant cycling of sickling seen with HbS?
Results in damage to the RBC membrane, leading to decreased flexibility
What are the clinical characteristics of sickle cell anemia?
- Anemia
- Jaundice with unconjugated bili
- Increased risk for bili gallstones
What happens to haptoglobin levels with sickle cell disease?
Decreased due to intravascular hemolysis
What are the PBS findings with sickle cell disease? Why?
- Target cells
- Dehydration of cells causes blebbing of RBCs with Hb accumulation in the blebs
What are findings of the erythroid hyperplasia seen with sickle cell disease?
Chipmunk facies
- Crewcut appearance of the skull on x-ray
- HSM
What are the complications that arise from the irreversible sickling that is seen with sickle cell disease?
Vasoocclusion and infarction of tissues
What is the common presenting sign of sickle cell disease in infants? Why?
Dactylitis–Vaso-occlusive infarct of bones with sickling
What causes the autosplenectomy seen with sickle cell disease?
Infarction of the spleen from vasoocclusion by sickled RBCs
What bacteria is the classic cause of osteomyelitis with sickle cell disease?
Salmonella paratyphi
What are the characteristics PBS findings with splenectomy?
Howell-Jolly bodies
What are the SHINE SKiS bacteria that patients with sickle cell disease are susceptible to?
- Strep pneumo
- HiB
- Neisseria meningitidis
- E. Coli
- Salmonella
- Klebsiella
- GBS
What is the most common cause of osteomyelitis overall?
Staph aureus
What is the acute chest syndrome seen with sickle cell disease? What are the s/sx of this?
- Vaso-occlusion in the pulmonary microcirculation
- Chest pain, SOB
What is the most common cause of death with sickle cell disease?
Acute chest syndrome
What usually precipitates episodes of acute chest syndrome in patients with sickle cell disease? Why?
- Pneumonia
- Causes vasodilation, which increases transit time for RBCs, and increases the chances that sickled RBCs will sickle and occlude
What are the renal sequelae of sickle cell disease? How does this present?
- Renal papillary necrosis
- Gross hematuria and proteinuria
How much HbS is needed to cause sickling? Why is this relevant?
More than 50%
-Explains why sickle cell trait does not lead to the same issues as sickle cell disease
Generally, RBCs in sickle cell trait do not sickle, and thus do not cause problems. There is one exception to this however. What is this? Why?
Renal medulla has extreme hypoxia and hypertonicity, causing microinfarctions, leading to progressive kidney damage
What are the clinical findings of renal medulla damage with sickle cell trait?
- Microscopic hematuria
- Decreased ability to concentrate urine
What is the chemical that can cause cells to sickle if HbS is present at all?
Metabisulfite
What happens to HbA with sickle cell disease?
Absent
What is the amino acid change that occurs with hemoglobin C? What is the inheritance pattern of this?
- AR mutation in beta chain
- Glutamic acid to lysine (“lys-ccc-ene”)
What is the classic PBS finding of HbC?
Hb C crystals
