Pathoma - RBC Disorders - Normocytic Anemia Flashcards
What are the two main causes of normocytic anemia and how do you differentiate them?
(1) Increased peripheral destruction
(2) Underproduction
Can differentiate the two via corrected reticulocyte count:
>3% = peripheral destruction
<3% = underproduction
What do reticulocytes look like and what is the normal reticulocyte count?
Large cells with bluish cytoplasm due to residual RNA
Normal reticulocyte count is 1-2%
How do you calculate corrected reticulocyte count
Reticulocyte count x (Hct/45)
What is haptoglobin?
Protein within the blood that binds hemoglobin to bring to the spleen to recycle the iron
What are the 2 types of peripheral RBC destruction and their clinical/laboratory findings?
Extravascular hemolysis (destruction of RBCs via reticuloendothelial system):
- Anemia with splenomegaly
- Jaundice due to unconjugated bilirubin
- Increased risk for bilirubin gallstones
- Marrow hyperplasia with retic count >3%
Intravascular hemolysis (destruction of RBCs within vessels):
- Hemoglobinemia
- Hemoglobinuria
- Hemosiderinuria (iron taken up by renal tubule being excreted with shedding tubular cells)
- Decreased serum haptoglobin (collects Hb within the blood to bring to the spleen)
What is hereditary spherocytosis and what type of anemia does it cause
Inherited defect of RBC cytoskeleton
Causes normocytic anemia due to extravascular hemolysis
Describe the mechanism behind RBC destruction in hereditary spherocytosis
Inherited defect of RBC membrane leads to blebs lost over time
Loss of membrane leads to formation of spherocytes (not enough membrane to create the normal disc shape)
Spherocytes cannot maneuver properly through spleen, so are destroyred by macrophages
What are the clinical and lab findings in hereditary spherocytosis
Spherocytes with loss of central pallor
Increased RDW (increasing membrane loss over time)
Increased mean corpuscular hemoglobin concentration (MCHC) - cell shrinks but cytoplasm stays the same, leading to increased Hb concentration
Splenomegaly, jaundice, and risk for bilirubin gallstones (increased RBC destruction in the spleen)
What is the osmotic fragility test and what does it test for?
Increased spherocyte fragility in hypotonic solution
Diagnostic for hereditary spherocytosis
What is the treatment for Hereditary spherocytosis and what clinical finding is there after treatment?
Splenectomy
Will resolve anemia (spherocytes are functional - anemia was caused by their destruction)
Splenectomy results in Howell-Jolly bodies (RBCs with fragments of nuclear material that would usually be removed by the spleen)
Describe the mutation in sickle cell anemia and how it results in anemia
Single amino acid change (from glutamic acid to valine) in the beta-chain of hemoglobin
HbS polymerizes (reversible) when deoxygenated, causing aggregation, leading to sickling of cells
What is protective against cell sickling?
HbF (a2d2) and treatment with hydroxyurea, which increases levels of HbF
How do sickle cells lead to anemia?
The continuous sickling and de-sickling leads to RBC membrane damage which causes:
- extravascular hemolysis
- intravascular hemolysis due to dehydration of RBCs (decreased haptoglobin and target cells)
What are the effects of erythroid hyperplasia due to sickle cell anemia?
Expansion of hematopoiesis to skull (‘crewcut’ appearance) and facial bones (‘chipmunk facies’)
Extramedullary hematopoeisis with hepatomegaly
Risk of aplastic crisis with parvovirus B19
What are the effects of vaso-occlusion in sickle cell anemia?
Vaso-occlusion caused by sickle cells obstructing vessels
Dactylitis (swollen hands and feet) - common presentation in infants
Autosplenectomy (due to vaso-occlusion of splenic artery)
Acute chest syndrome (vaso-occlusion of pulmonary microcirculation)
Pain crisis
Renal papillary necrosis (resulting in gross hematuria and proteinuria)
What is the most common cause of death in adults and children with sickle cell disease?
Children - infection with encapsulated organisms due to autosplenectomy
Adults - acute chest syndrome
What is the metabisulfite screen?
Causes cells to sickle with any amount of HbS
Will be positive in disease and in trait
Usually cells do not sickle with trait because RBCs need > 50% HbS in order to sickle
What will Hb electrophoresis reveal in sickle cell disease and trait?
Disease:
90% HbS; 8% HbF; 2% HbA2; No HbA
Trait:
55% HbA; 43% HbS; 2% HbA2
What is the mutation in Hemoglobin C?
Single amino acid mutation (from glutamic acid to lysine) in the beta globin chain
What are the effects of Hemoglobin C
Mild anemia due to extravascular hemolysis
Characteristic HbC crystals
What are some of the causes of anemia caused by intravascular hemolysis?
Paroxysmal nocturnal hemoglobinuria
G6PD Deficiency
Immune hemolytic anemia
Microangiopathic hemolytic anemia
Malaria
What is paroxysmal nocturnal hemoglobinuria (PNH)
Acquired defect in myeloid stem cells resulting in absent GPI (which is the anchoring protein for surface receptors that protect RBCs against complement)
Why does intravascular hemolysis occur at night in paroxysmal nocturnal hemoglobinuria?
Shallow breathing at night leads to mild respiratory acidosis, which activates complement
What test confirms the diagnosis of paroxysmal nocturnal hemoglobinuria?
Flow cytometry detecting lack of CD55 (aka DAF)
DAP and MIRL are the surface proteins that usually bind to GIP to protect against complement
