BIIC Pathology Lecture 1_Hemolytic Anemias Flashcards
How large should the zone of central palor be in a RBC?
About 1/3rd the diameter of the cell
What causes the distruction of a typical erythrocyte?
After 120 days defects in their cytoskeleton and ion transport begin to appear. These defects make the RBC less flexible and causes it to get stuck in the spleen where it is eaten by phagocytes
What are the typical values of Hb and hematocrit in men and women
Men: 13.6-17.2 gm/dL and 39-49% Women: 12-15 gm/dL and 33-34%
What are typical clinical findings of all anemias?
Pale, weakness, malaise, fatige, dyspnea on mild exertion
What are hemolytic Anemias?
They are a diverse group of anemias charicterized by the accelerated destruction of RBCs. They include intravascular hemolysis and extravascular hemolysis (typically in the spleen)
What are the two typical microscope findings in hemolytic anemias? what is the mechanisium?
1) Erythroid hyperplasia and 2) reticulocytosis Low O2 levels stimulate the kidney to secrete extra EPO. This leads to increased RBC production (Erythroid hyperplasia) and more reticulocytes (reticulocytosis)
What are the three major clinical indication of chronic extravascular hemolysis?
Anemia, splenomegaly (note a splenectomy can improve this), jaundice
What causes intravascular anemia?
ANy significant damage to the RBC membrane (mechanical, biochemical, etc)
What are the 5 common lab findings in intravascular hemolytic anemias?
Hemoglobinemia, hemoglobinuria, hemosiderinuria, decreased serum haptoglobin, loss of iron
What is the inheritance pattern of hereditary spherocytosis?
typically autosomal dominant
Mutations to which proteins typically cause Hereditary spherocytosis?
ankyrin, band 3, and spectrin
What is a major microscope finding of Hereditary Spherocytosis?
Lack of central palor
What is a major impact to the liver of hemolytic anemias? Why?
Extra bilirumin to the liver. This is because increased rate of RBC destruction (which causes splenomegaly) results in more heme which is turned into bilirubin (can cause jaundice) and excreted in the stool. Increased bilirubin can cause cholelithiasis (galstones)
Which virus is particularly dangerouse for people suffering from hemolytic anemia?
Parvovirus B19. This is because Parvo B19 sets up shop in progenitor blood cells (and kills them). This is a huge problem for people with increased RBC turn over
Take time to describe the MOA of G6PD (review biochem notecards if needed).
sweet as
What is the inheritance pattern of G6PD?
recessive X linked
Describe G6PD A. Who is at risk for it and what is the MOA?
One is G6PD A-, which is carried by ~10% of black males in the United States. ✦ G6PD A- has a normal enzymatic activity, but a decreased half-life.
Describe G6PD Mediterranean
G6PD Mediterranean, found mainly in the Middle East, the enzyme deficiency and the hemolysis that occur on exposure to oxidants are more severe.
Why is G6PD often episodic?
Because hemolysis is caused by exposure to ROS. Things that increase the exposure to ROS (some medications, and infections) will cause acute episodies of increased hemolysis
What medications are contraindicated in G6PD deficency
anti-malerials, sulfonamides,nitrofurantoin, phenacetin
What is the inheritance pattern of Paroxysmal Nocturnal Hemoglobinuria (PNH)
PIGA is an x linked mutation
PNH causes a loss of which proteins?
CD55, CD59, C8 all of which are complement proteins and some of which inhibit the pathway. This mutation causes RBC to be abnormally susceptible to lysis or injury by complement causeing intravascular hemolysis
Why does PNH happen at night?
The nocturnal hemolysis that gives PNH its name occurs because complement fixation is enhanced by the decrease in blood pH that accompanies sleep (due to CO2 retention).
What is a key microscope finding with G6PD deficiency?
Bite cells. This is where macrophages in the spleen have “bitten out” the heizen bodies
Describe the mechanisium that causes PNH
What does hemolytic trauma do to cells?
