Lecture 12 Chapter 24 Flashcards
Hemoglobinopathies are due to
Improper or lack of production of globulin chains for the hemoglobin
Which chromosome carry’s the genes for the beta hemoglobin family
Human chromosome 11
Which chromosome carry’s the genes for the alpha hemoglobin family
Human chromosome 16
In all cases of hemoglobinopathies there is a
Structural and functional problem with the hemoglobin
What mutation causes sickle cell anemia
On amino acid #6 of a beta globulin chain, a single nucleotide mutation causes glutamic acid to be replaced by valine
What causes hemoglobin C
On amino acid #6 of a beta globulin chain, a single nucleotide mutation causes glutamic acid to be replaced by lysine
What causes hemoglobin E
On amino acid #26 of a beta globulin chain, a single nucleotide mutation causes glutamic acid to be replaced by lysine
What happens when a child is born with a beta chain mutation
The effects of the mutation will not take effect until after birth
What happens if you have a mutation in your alpha chain
The effects of the mutation will begin while in utero
What are the differences between proteins when a mutation occurs on amino acid #6 changing glutamine to valine in sickle cell anemia
Normal protein: -1 charge, hydrophilic, interactive with water
Sickle cell: 0 charge, hydrophobic, runs away from water, hemoglobin will crystallize changing the shape of the cell.
Protein shape won’t be maintained any more
What causes sickleing of cells
Decrease in oxygen levels
What is zygosity
You have multiple copies of genes: beta has two copies, one on each chromosome 11, alpha has 4 copies, two on each chromosome 16.
Depending on the combination of these copies and the mutations that are present or not present, you will have completely different symptoms
When abnormal hemoglobin come out of the bone marrow
It looks completely normal, the morphology doesn’t change until the oxygen level goes down
Where is there the least oxygen in the body and what happens to the mutated cells
The tissues contain the least oxygen which then causes vasal occlusion, or obstruction of the blood vessels. If it happens in brain = stroke; in heart = heart attack; kidney = nephrectomy; liver = liver disease
Describe the shape of a sickle cell and what problems it poses
The membrane is in tact, but it has polymerized causing everything to be in one corner
These cells cannot go through small capillaries, arterials, venules
What causes the polymerization of sickle cells
When glutamic acid is replaced by valine the charge is changed and the hemoglobin molecules are now hydrophobic but surrounded by water. So the hemoglobin molecules clump together by fitting in each other’s crevices
What happens to a person’s spleen when they have sickle cells
The spleen will try to remove the sickle cells which causes splenomegaly and it can cause autosplenectomy because it happens so much their spleen dies.
What correlation does malaria have with the sickle cell trait (AS)
You will be very immune to malaria
What is the #1 killer of children under the age of 5
Malaria
Why is sickle cell and thalassemia still here today while malaria isn’t as common anymore
Sickle cell and thalassemia effects won’t begin until 20-30 years after birth, allowing them to have children and pass down the trait, while malaria kills almost instantly
Where is malaria still present, how many forms are there, and what are they
6 kinds throughout Europe, Asia, Arica, South America
Thalassemia - middle Eastern Europe, Southern Asia, east and South Africa
HbS - west and Middle Africa, some small parts of Eastern Europe
HbC - Western Africa
Ovalocytosis - South Asia
HbE - South Asia
Pk deficiency - Eastern Europe
Why is sickle cell disease so deadly
Basal cell occlusion in the blood cells due to low oxygen
What can activate sickle cell disease and what are some symptoms
Airplanes if the oxygen levels are too low
Causes numbness and pain in fingers and toes
At what age does sickle cell disease symptoms begin
6 months to 1 year old, before that, child will be normal
At what age do thalassemia symptoms begin
At birth
What is the main problem in Hgb S
Vasoocclusion
What does the frequency of vasoocclusion depend on?
Lifestyle: what’s your job? What do you do? Heavy exercise lowers oxygen in tissues
What type of anemia is hemoglobin S
Extra vascular hemolysis
What types of cells will be seen in a blood smear for Hgb S
Normocytes (cells are normal when exiting the BM)
Target cells
Sickle cells (in crisis = a lot)
Based on severity, if spleen is involved: pakilocytosis; dacryocytes; HJ bodies, nRBCs
MCV, RDW, cell count, and bone marrow results for those with Hgb S
Normal MCV
Increased RDW
Elevated RBCs
BM = hypercellular
Describe the tube solubility test for Hgb S
A tube holds a buffer that contains a solution that will bind to oxygen and remove it. Patients blood is added to the buffer, and it will remove the oxygen. If you have sickle cell/Hgb S it will cause sickleing of the cells which increases the turbidity (cloudiness). If you do not have it, the mixture will be see through/have clarity. Will be positive with even 1 sickle cell
What is the expected hemoglobins and their amounts in a normal person
A2 = 3-5%
F = 1-2%
A = about 95%
Name the diseases based on the gel electrophoresis results
What happens because of the change from glutamic to lysine in Hgb C
The charge changes from -1 to +1 which changes the shape of the hemoglobin molecule and causes polymerization of that molecule, which causes crystallization of Hgb into “rod-like” shapes
Why is Hgb C not as deadly as Hgb S
Due to the shape of the crystal, it is small enough to not cause vasal occlusions and will be removed after ~30 days
How can Hgb C cause gallstones
RBCs end up getting removed early on, so the turn around of the cells will be high. This increases the production of bilirubin, bilirubin goes to liver, then gets put in the bile. If you have a high concentration of bilirubin, which increases your chance of developing a gallstone in your bile
What is the MCV, MCHC, and reticulocyte counts on a blood smear for someone with Hgb C
MCV = normal
MCHC = normal or elevated
Retic count = elevated
What types of cells will be seen in a blood smear for Hgb C
Target cells
Rod-shaped crystals
What type of anemia is hemoglobin C
Extravascular anemia
What do you expect to see on a blood smear for someone with Hgb E
Target cells
VERY microcytic cells (~55 MCV)
Hypochromic
Where is Hgb E most prominent and why does that pose as an issue
Southeast Asia: Thailand, Philippines, Indonesia, Malaysia
This region also has a high rate of genetic mutations for thalassemia, sickle cell, Hgb C which can sometimes result in a combination of 2 diseases at the same time
What can cause a more severe form of sickle cell disease?
If someone with the sickle cell trait has a child with someone with Hgb E, and that child has the “S” and ”E” gene, it will result in the child having Hgb S
What are the properties of cells with Hgb SC
Amorphous
Uneven distribution of Hgb in the call due to polymerization. Hemoglobin may clump on one side leaving one side much darker and the other hypochromic
Characteristics of Hgb SC
More severe than sickle cell trait and can cause vasal occlusions but the frequency is not as high as Hgb S.
Those with Hgb SC are prone to develop retinopathy, crystals develop in retinas/eyes
What can be seen on a blood smear with Hgb SC
Target cells
Amorphous crystals
Can have sickle cells but not dominant
