ICL 3.2: Structural & Enzymatic Disorders

Question 1

what are the most common proteins in RBC cell membranes?

Answer 1

• ankyrin
• spectrin
• band 3

Question 2

how is hereditary spherocytosis inherited?

Answer 2

autosomal dominant

Question 3

what population is mostly effected by hereditary spherocytosis?

Answer 3

caucasian

northern european

Question 4

what is hereditary spherocytosis?

Answer 4

spectrin or ankyrin deficiency!!

membrane loss leads to spherocytes

these misshapen RBCs are destroyed in the spleen = extravascular hemolysis

Question 5

what are the clinical symptoms of hereditary spherocytosis?

Answer 5

anemia

jaundice

splenomegaly

gallstones

Question 6

what test is done for hereditary spherocytosis?

Answer 6

1. osmotic fragility test

RBCs are more likely to lyse in a hypotonic solution

incubate for 24 hours first before testing or you can get 25% false negative

2. auto-hemolysis test

incubate cells in their own plasma for 48 hours, normally 5% lyse but in HS 10-50% will lyse

Question 7

how do you treat hereditary spherocytosis?

Answer 7

splenectomy

no spleen = no spherocytes being removed!

better for adults though, kids need their spleen

you have to give them encapsulated organism vaccines though now that they don’t have a spleen

Question 8

what is hereditary elliptocytosis?

Answer 8

inherited blood disorder in which an abnormally large number of RBCs are oval or elliptical shaped

leaves to chronic hemolysis of weird RBCs

Question 9

how do you treat hereditary elliptocytosis?

Answer 9

remove the spleen lol

Question 10

what is hereditary stomatocytosis?

Answer 10

autosomal dominant

lack of protein 7.2 (stomatin)

outside of the RBC shape looks fine but the inside of the cell looks like a white line

leads to hemolysis of RBCs

Question 11

how do you treat hereditary stomatocytosis?

Answer 11

don’t do a splenectomy!

usually causes more clots for some reason

Question 12

what is hereditary pyropoikilocytosis?

Answer 12

HPP is autosomal recessive

unstable spectrin causes unstable membrane cytoskeleton

both spectrum genes from mom and dad are abnormal so every cell in the blood smear is abnormal!!

Question 13

what is PNH?

Answer 13

paroxysmal nocturnal hemoglobinuria

rare, acquired genetic clonal stem cell defect

PIG-A gene mutation results in lack of membrane CD55 and CD59

if anchor protein isn’t made, there’s holes in the RBC and the RBC gets lysed

causes C-mediated intravascular lysis of ALL cells (WBC, RBC, platelets)

Question 14

what mutation causes PNH?

Answer 14

PIG-A gene mutation leading to deficiency of glycosylphosphatidylinositol anchor protein in RBC

Question 15

what is haptoglobin?

Answer 15

it’s a suicide molecule

it gives itself up to get rid of all the toxic molecules coming out of a cell when it gets hemolyzed

Question 16

what are the signs of PNH?

Answer 16

chronic hemolysis

anemia, jaundice, gallstones

venous thrombosis

clinical triad: hemolysis, pancytopenia, thrombosis

Question 17

what tests can be done to test for PNH?

Answer 17

1. Ham test: put RBCs in acidic solution to see if they hemolyze
2. cytometric analysis

Question 18

what is a cytometric analysis and how is it used to diagnose PNH?

Answer 18

tests to see if CD55 and CD59 are present

normal cells have CD59 and CD55 present at the same time

go look at the figure in your notes

Question 19

what’s the treatment for PNH?

Answer 19

Soliris antibody

completely stops PNH

Question 20

what’s the inheritance of G6PD deficiency?

Answer 20

x-linked recessive

males are more likely to have it

Question 21

what are the classes of G6PD deficiency?

Answer 21

class I-V

Question 22

what is class I G6PD deficiency?

Answer 22

sever enzyme deficiency, <1% normal enzyme activity

chronic hemolysis

Question 23

what is class II G6PD deficiency?

Answer 23

<10% enzyme activity

intermittent hemolysis

drug induced

Question 24

what is class III G6PD deficiency?

Answer 24

mild to
10-60% enzyme activity

moderate enzyme deficiency

intermittent hemolysis

Question 25

what is what is class IV G6PD deficiency?

Answer 25

very mild enzyme deficiency

60-90% enzyme activity

no clinical problem

Question 26

what is class V G6PD deficiency?

Answer 26

very mild enzyme deficiency

> 110% enzyme activity

no clinical problems

Question 27

what can cause G6PD deficiency?

Answer 27

1. drugs: antimalarials, sulfonamides, nitrofurantoin, antipyretics, analgesics
2. herbal medicines
3. moth balls
4. insecticides & fungicides
5. fava beans
6. food coloring with aniline dyes
7. potential oxidant agents during certain illness

Question 28

what does pyruvate kinase deficiency cause?

Answer 28

without pyruvate kinase in the glycolysis pathway, PEP can’t be turned into pyruvate to make ATP

in RBCs this is the only way they can make energy because they don’t have mitochondria!

so without pyruvate kinase, there’s RBC hemolysis