BIIC Pathology Lecture 1_Hemolytic Anemias

Question 1

How large should the zone of central palor be in a RBC?

Answer 1

About 1/3rd the diameter of the cell

Question 2

What causes the distruction of a typical erythrocyte?

Answer 2

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

Question 3

What are the typical values of Hb and hematocrit in men and women

Answer 3

Men: 13.6-17.2 gm/dL and 39-49% Women: 12-15 gm/dL and 33-34%

Question 4

What are typical clinical findings of all anemias?

Answer 4

Pale, weakness, malaise, fatige, dyspnea on mild exertion

Question 5

What are hemolytic Anemias?

Answer 5

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)

Question 6

What are the two typical microscope findings in hemolytic anemias? what is the mechanisium?

Answer 6

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)

Question 7

What are the three major clinical indication of chronic extravascular hemolysis?

Answer 7

Anemia, splenomegaly (note a splenectomy can improve this), jaundice

Question 8

What causes intravascular anemia?

Answer 8

ANy significant damage to the RBC membrane (mechanical, biochemical, etc)

Question 9

What are the 5 common lab findings in intravascular hemolytic anemias?

Answer 9

Hemoglobinemia, hemoglobinuria, hemosiderinuria, decreased serum haptoglobin, loss of iron

Question 10

What is the inheritance pattern of hereditary spherocytosis?

Answer 10

typically autosomal dominant

Question 11

Mutations to which proteins typically cause Hereditary spherocytosis?

Answer 11

ankyrin, band 3, and spectrin

Question 12

What is a major microscope finding of Hereditary Spherocytosis?

Answer 12

Lack of central palor

Question 13

What is a major impact to the liver of hemolytic anemias? Why?

Answer 13

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)

Question 14

Which virus is particularly dangerouse for people suffering from hemolytic anemia?

Answer 14

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

Question 15

Take time to describe the MOA of G6PD (review biochem notecards if needed).

Answer 15

sweet as

Question 16

What is the inheritance pattern of G6PD?

Answer 16

recessive X linked

Question 17

Describe G6PD A. Who is at risk for it and what is the MOA?

Answer 17

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.

Question 18

Describe G6PD Mediterranean

Answer 18

G6PD Mediterranean, found mainly in the Middle East, the enzyme deficiency and the hemolysis that occur on exposure to oxidants are more severe.

Question 19

Why is G6PD often episodic?

Answer 19

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

Question 20

What medications are contraindicated in G6PD deficency

Answer 20

anti-malerials, sulfonamides,nitrofurantoin, phenacetin

Question 21

What is the inheritance pattern of Paroxysmal Nocturnal Hemoglobinuria (PNH)

Answer 21

PIGA is an x linked mutation

Question 22

PNH causes a loss of which proteins?

Answer 22

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

Question 23

Why does PNH happen at night?

Answer 23

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).

Question 24

What is a key microscope finding with G6PD deficiency?

Answer 24

Bite cells. This is where macrophages in the spleen have “bitten out” the heizen bodies

Question 25

Describe the mechanisium that causes PNH

Answer 25

Question 26

What does hemolytic trauma do to cells?

Answer 26