Lecture 14 Chapter 21

Question 1

Intrinsic causes vs extrinsic causes

Answer 1

Intrinsic = the problem is within the blood cell
Extrinsic = the problem comes from someplace else

Question 2

What groups of diseases are intrinsic

Answer 2

Hemoglobinopathies
Membranopathies
Enzymopathies

Question 3

What 2 proteins are responsible for the connection of the inner proteins to the membrane proteins

Answer 3

Ankyrin
Band 3.1

Question 4

What happens when there is a mutation in the protein that holds the cell membrane to the cytoskeleton

Answer 4

The outer membrane becomes loosened (not connected to cytoskeleton inside cell)
Cell goes to spleen and macrophages will attack the young cell, but the young cell will fight back so the macrophage will only get a piece of the membrane and the cell want lose any volume = spherocytes (less surface area compared to volume)

Question 5

What happens when the spherocyte gets to the spleen

Answer 5

It will get caught and will not be able to form into a large cell, but is still too big for the splenic vessel, so it will get stopped there, causing severe anemia
If anemia is very severe, it is called hereditary spherocytosis which then causes a splenectomy as treatment, because all of the hemolysis is happening in the spleen

Question 6

What is the bilirubin level of someone with hereditary spherocytosis and is it conjugated or unconjugated

Answer 6

Elevated bilirubin
Unconjugated because there is no problem with the liver (liver can hold a lot of bilirubin)

Question 7

What happens when the concentration of bilimbin is too high

Answer 7

Allows for crystallization and causes gallstones

Question 8

What happens when there is a mutation in the horizontal proteins

Answer 8

These proteins are responsible for the maintenance of the structural integrity of the cell
When there’s a mutation a RBC cannot regain its normal shape after going through a narrow capillary, usually becoming an elliptocyte = hereditary elliptocytosis

Question 9

What happens when there is hemolysis in a blood sample

Answer 9

Results will show an increase in K+ since there is a higher concentration of K+ inside the cell. A new blood sample must be drawn for accurate K+ results

Question 10

What causes hereditary spherocytosis

Answer 10

Mutation in the vertical protein

Question 11

What is the standard “golden” test for hereditary spherocytosis

Answer 11

Osmotic fragility = put specific volume of the blood into progressively hypotonic saline solutions → incubate for 2 hours → measure the hemolysis with spectrophotometer
Osmotic fragility will increase meaning the cells will rupture much faster in less hypotonic solution

Question 12

If you have a splenectomy how does that affect spherocytes

Answer 12

You will see more spherocytes and more RBC inclusions

Question 13

In order to identify spherocytes what 3 conditions must be met

Answer 13

1. Spherocytes will be smaller
2. No central pallor
3. Hyperchromic

Question 14

What causes hereditary elliptocytosis

Answer 14

Mutation in the horizontal protein

Question 15

What is the move severe form of elliptocytosis

Answer 15

Pyropoikilocytosis

Question 16

How can you identify pyropoikilocytosis

Answer 16

Predominant = elliptocytes
Cells are sensitive to heat

Question 17

What % of cells are stomatocytes in a normal blood smear

Answer 17

2-3%

Question 18

What happens when stomatocytes get to the spleen

Answer 18

They will get caught which can cause mild/moderate anemia

Question 19

Where are stomatocytes formed

Answer 19

Bone marrow and liver
Splenectomy = not helpful

Question 20

How many classes does G6PD deficiency have and how are they measured

Answer 20

5 classes
Degree of anemia decreases from class I to class V

Question 21

What does G6PD class V mean

Answer 21

G6PD activity increases making you more immune to oxidative environments, can respond better

Question 22

What does G6PD class I mean?

Answer 22

Reduces G6PD activity to 5% = severe/chronic anemia
Sepsis/fever/infection = can cause a crisis hemolyzing cells

Question 23

What happens when there is not much G6PD activity

Answer 23

Hemoglobin oxidizes → becomes Heinz bodies → Heinz bodies deposit inside RBCs → accumulate at the inner part of the membrane → red blood cell goes to spleen → macrophage takes a bite of the precipitated Heinz bodies in the inner part of the membrane → takes the membrane and part of the cytoplasm

Question 24

What is G6PD class 2

Answer 24

People very susceptible to fava beans
Fava beans create a very oxidative environment in body
If you eat fava beans, your cells will hemolyze after a few hours
Can also be drug induced (chemotherapy, antibiotics, malaria medication) and infection induced (sepsis)

Question 25

What is the expected reticulocyte count and Chemistry test results for G6PD deficiency

Answer 25

Retic count = elevated
Chem tests = elevated LDH, K+; haptoglobin is decreased

Question 26

What is haptoglobin and its function

Answer 26

A protein produced by the liver
Function = bind to free hemoglobin

Question 27

One of the best signs to identify whether or not someone is having intravascular hemolysis

Answer 27

When haptoglobin is non-detected

Question 28

What happens when you do not have pyruvate kinase

Answer 28

Cannot make pyruvate → phosphoenolpyruvate increases → 1,3-biphosphoglycerate increases → 2,3-BPG increases

Question 29

What happens when you have increased 2,3-BPG

Answer 29

The release of oxygen from hgb is much easier from higher concentration

Question 30

What are the conditions in which you will have echinocytes

Answer 30

1. Artifact (old blood)
2. Any condition that causes an increase in urea
3. 30% of cells in PK deficiency