All right welcome back, so we have been talking about anemia,
microcytic anemia, now we're talking about
Thalassemia...in the last video we have talked about alpha-thalassemia (link in description). Today. We'll talk about beta thalassemia
So, Beta Thalassemia is a microcytic anemia, and again symptoms of anemia
Tired and pale, pale and tired...sometimes, I have murmur (flow murmer), sometimes I can get angina.
also...
exercise intolerance,
fatigue,
Etc. Beta thalassemia is very common in Italy so keep that in mind, okay?
So, as you know...
Hemoglobin has two alpha subunits, and two beta subunits...good
They are called
tetramers
excellent
Thalassemia by definition is a defect in globin
chain
synthesis
good, so this will lead to
two things; here you have the globin so
Decreased globin synthesis will lead to decreased hemoglobin
i.e. anemia
Good...what else?
when globin chain
Synthesis unbalanced hemo tetramers form so for example when alpha is not
present beta will form tetramers
They are insoluble
They will precipitate in RBC's. The spleen macrophages will recognize that and will cause hemolysis
Will destroy these abnormal RBCs.
this will lead to...
ineffective
erythropoiesis
Why? -Bone marrow tries to respond to the hemolysis by producing more...
red blood cells. However,
Globin synthesis decreas; I cannot synthesize
Good RBC's, or sufficient RBC's. It's called ineffective
erythropoiesis
beta thalassemia
The problem is in chromosome 11
Do you remember what chromosome was involved in alpha-thalassemia?
Correct! - 16 ...Okay, how to remember beta and 1? -just draw beta like this:
And then draw an 11 like this.
Okay, so we can do it better. This is the 11 and then this is the beta, like this.
Just any way to remember, okay, it's common in the Mediterranean, Middle Eastern and
Asian population...Please, remember Greece and Italy.
Greece and Italy beta thalassemia
chromosome 11
Beta thalassemia can be mild or severe
Mild anemia usually due to a splicing defect
Go back to your
Molecular Biology and review this topic.
Severe anemia is due to a specific type of point mutation, called: nonsense mutation
There is a stop codon. Okay? That's introduced...
Earlier than usual. Stop codons are these as you know this will lead to termination...
Of protein synthesis, and in this case the protein is
the beta
globin
-in = protein
So, genetically speaking beta thalassemia can be either
heterozygous or
Homozygous
Heterozygous is beta thalassemia minor
homozygous can be either:
thalassemia intermediate or beta thalassemia major
chromosome 11
so, number one beta thalassemia minor
there is
Increase in the number of microcytic RBCs, of course.
Thalassemia is a microcytic anemia. However, in thalassemia
There is increased number of RBC's. Nobody know why!!!
That's interesting so when you have microcytic anemia low hemoglobin, low hematocrit,
but, (and that's a big but)
RBC count is a little bit high
Iron studies are normal, please suspect thalassemia.
Beta thalassemia minor; it's minor, so it's either asymptomatic or there is minor anemia
So what will happen to the normal adult hemoglobin A? - it will slightly decrease
Hemoglobin A2 will increase, hemoglobin F will slightly increase.
so,
Hemoglobin electrophoresis will show this. Hemoglobin electrophoresis in beta thalassemia minor is...
abnormal
Contrast that with the minor form of alpha-thalassemia, called:
the Alpha thalassemia trait
Trait you remember? Trait, where the hemoglobin electrophoresis was completely normal!
Alrighty, now the big one; Beta thalassemia major (also known as Cooley's anemia)
so, we start here by a problem in the
Beta globin production... Zero; there is none whatsoever; no beta globin production.
So what else do we have other than the beta? -Alpha... Alpha globin will form and precipitate forming...
Homo-tetramers, and these homotetramers will lead to two things:
first in the bone marrow...
the RBC's containing the Homotetramers will die...
Earlier before being released... why? - they are not healthy, they cannot survive.
So, they die... This is called ineffective
Erythropoiesis, as you know. What else will happen to these...
homotetramers? - they will precipitate in RBCs, so the
Macrophage in the spleen will recognize these
Oh, these are ill, abnormal RBCs, let's kill them!!! :O
So, they destroy the RBC', which leads to hemolytic anemia.
Hemolytic anemia? - the kidney will respond by increasing
Erythropoietin production
erythropoietin will lead to something called...
Erythroid hyperplasia
Erythroid is the cell line that produces RBC's and...
hyperplasia means increasing the number of cells, so we increased number of RBC's and...
We increase the formation, increased production in the bone marrow...
This is called: medullary
erythropoiesis
Fine. But, I need more, I need more factories to produce more RBC's, so
the spleen and the liver , or the
reticulo-endothelial organs
will take over. It's called extra-medullary
Hematopoiesis. They will start forming new
RBCs
Ok, they are working really hard. They will enlarge...
"hepatosplenomegaly"
Fine, the medullary cavity
inn the skull, and in the bones will enlarge. When they enlarge,
This will include the skull who give us an appearance on x-ray called hair on end appearance or
crew-cut
skull Crew-cut-hair skull
Also, the maxilla: the maxillary bone will enlarge leading to something called chipmunk facies
fine!
So, hemolytic anemia...so we need to give the patient blood.
Giving them blood? -we will make them
dependent on the
transfusion or transfusion-dependent
This blood contains iron, which will lead to iron overload...
Hemosiderosis and
secondary
hemochromatosis...What else?
anemia; hemolytic anemia is destruction of the
Hemoglobin, and hemoglobin has heme and globin.
Haeme has iron and protoporphyrin. Protoporphyrin will convert to unconjugated bilirubin, goes to the liver to be
Conjugated into the conjugated bilirubin
Okay, so this increase in unconjugated bilirubin
Will lead to unconjugated
hyperbilirubinemia
and of course
jaundice!
That's it for beta thalassemia major...if you understand this slide, you will know a lot of
information for your exam :)
Now, the last one: Beta thalassemia intermedia
It's an intermediate form it's not as severe as major, but it's also more severe than the minor beta thalassemia
So there is an a
Co-inheritance with alpha thalassemia trait. so, when you have beta thalassemia intermedia, usually you have also
alpha-thalassemia
trait
fine!
Okay, so there is also minor
Qualitative defect in the beta globin, so usually we have alpha and beta
Remember in beta thalassemia major, we don't have any beta. So, the Alpha
Increased forming Homotetramers. However in this condition. I have also alpha-thalassemia trait I have
Deficiency in this alpha globin chains, so I cannot increase them as much I cannot
Produce as much homotetramers, so there is less homotetramers
Than beta thalassemia major...There is less
Hemolysis, and of course, hemoglobin F Will increase since you don't have beta.
What will happen? -Gamma change will form when you have alpha and gamma. This is called
Hemoglobin F, the fetal hemoglobin.
Okay, that's it for thalassemia, guys
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