Sickle Cell Disease | Pathophysiology, Symptoms and Treatment
Summary
TLDRThis video provides an in-depth explanation of sickle cell disease, a hereditary blood disorder characterized by sickle-shaped red blood cells. It covers the genetic basis, where the disease is inherited in an incomplete autosomal dominant fashion, and explains how a point mutation in the hemoglobin beta globin chain leads to the abnormal shape. The pathophysiology, including RBC sickling, hemolysis, and vaso-occlusion, as well as acute and chronic complications such as pain, anemia, and organ damage, are discussed. Diagnosis and treatment options, including hydroxyurea and bone marrow transplants, are also highlighted.
Takeaways
- ๐งฌ Sickle cell disease is a hereditary blood disorder characterized by sickle-shaped red blood cells.
- ๐งฌ It is inherited in an incomplete autosomal dominant fashion, where individuals with two copies of the affected allele are fully affected.
- ๐งฌ People with one affected allele have sickle trait, which offers some protection against malaria but causes less severe symptoms.
- ๐งฌ The disease is caused by a single point mutation in the hemoglobin beta-globin chain, substituting glutamic acid with valine at position six.
- ๐ฌ Sickle-shaped red blood cells can clog small blood vessels, leading to painful vaso-occlusion and increased risk of organ damage.
- ๐ฌ Red blood cells in sickle cell disease have a shorter lifespan (around 17 days) compared to normal red blood cells (120 days).
- ๐ Acute complications include severe anemia, infections, and pain caused by the sickling of red blood cells during stress conditions like hypoxia and dehydration.
- ๐ฉบ Chronic complications include hemolytic anemia, chronic pain, delayed growth, and neurological, renal, and cardiovascular issues.
- ๐งช Sickle cell disease can be diagnosed through prenatal testing, newborn screening, and hemoglobin electrophoresis.
- ๐ Hydroxyurea is a common treatment that reduces pain episodes and prolongs survival, while bone marrow transplants offer a potential cure for patients under 16.
Q & A
What is sickle cell disease?
-Sickle cell disease is a group of hereditary blood disorders characterized by sickle-shaped red blood cells.
How is sickle cell disease inherited?
-Sickle cell disease is inherited in an incomplete autosomal dominant fashion. Individuals with two copies of the affected allele (homozygous) are fully affected, while those with one copy (heterozygous) are carriers and can be slightly affected.
What is the difference between individuals with sickle cell disease and those with sickle cell trait?
-Individuals with sickle cell disease are homozygous for the hemoglobin S allele, while those with sickle cell trait are heterozygous and experience milder or no symptoms.
Why does the sickle cell mutation persist in certain populations?
-The sickle cell mutation provides protection against malaria, which is why it persists in populations where malaria is prevalent.
What causes the abnormal shape of red blood cells in sickle cell disease?
-A single point mutation on the hemoglobin beta globin chain changes glutamic acid to valine at position six, causing hemoglobin S. When deoxygenated, hemoglobin S is less soluble and aggregates, leading to red blood cell sickling.
What complications arise from sickle-shaped red blood cells?
-Sickle-shaped red blood cells can get trapped in small blood vessels, leading to vascular occlusion, hemolysis, and inflammatory responses, which cause pain, anemia, and other complications.
How long do sickle-shaped red blood cells live compared to normal red blood cells?
-Sickle-shaped red blood cells have a significantly reduced lifespan, living about 10 to 20 days compared to normal red blood cells, which live around 120 days.
What are some of the acute complications of sickle cell disease?
-Acute complications include an increased risk of infections, severe anemia, and vaso-occlusive pain due to sickled red blood cells blocking blood vessels.
What are some chronic complications of sickle cell disease?
-Chronic complications include chronic hemolytic anemia, pain, neurologic deficits, pulmonary issues, renal problems, osteoporosis, cardiomyopathy, delayed growth, and chronic leg ulcers.
What treatments are available for sickle cell disease?
-Treatment options include hydroxyurea, which reduces pain episodes and hospitalizations, blood transfusions for severe anemia, and hematopoietic cell transplantation, which is considered a potential cure for individuals under 16 years old.
Outlines
๐ฌ Understanding Sickle Cell Disease
Sickle cell disease is a hereditary blood disorder characterized by the presence of sickle-shaped red blood cells. The condition is inherited in an incomplete autosomal dominant pattern. Individuals with two copies of the affected gene are homozygous and fully affected, while those with one copy are heterozygous carriers (sickle cell trait) with milder symptoms. The mutation has been linked to protection against malaria, which is why it persists in populations where malaria is common.
๐ฉธ Pathophysiology and Hemoglobin Mutation
The root cause of sickle cell disease lies in a mutation of the beta-globin chain of hemoglobin, where glutamic acid is replaced by valine at position six. This single-point mutation results in the formation of hemoglobin S, which tends to aggregate when deoxygenated, leading to the sickling of red blood cells. These misshapen cells get trapped in the microvasculature, leading to occlusion, hemolysis, and a dramatically shortened lifespan of sickle red blood cells (around 17 days compared to 120 days for normal cells).
โ ๏ธ Acute and Chronic Complications of Sickle Cell Disease
Patients with sickle cell disease face increased risks of infections and severe anemia due to the sickling of red blood cells. Conditions like fever, dehydration, hypoxia, and acidosis exacerbate the problem. The sickling causes vaso-occlusion, leading to painful episodes, stroke, acute chest syndrome, renal infarction, myocardial infarction, and other complications. Over time, the disease leads to chronic hemolytic anemia, where the body tries to compensate by producing more immature red blood cells (reticulocytes). Blood smears show features like polychromasia and Howell-Jolly bodies.
๐ฉบ Long-term Effects and Diagnostic Approaches
Chronic complications include pain from vaso-occlusion, neurological deficits, pulmonary conditions, renal hypertension, osteoporosis, and more. Diagnosing sickle cell disease involves prenatal testing, newborn screenings, high-performance liquid chromatography, and hemoglobin electrophoresis. A diagnosis is confirmed if more than 30% of hemoglobin is found to be hemoglobin S.
๐ Treatment and Management of Sickle Cell Disease
The main treatments for sickle cell disease include hydroxyurea, which reduces pain episodes, hospitalizations, and improves survival, and bone marrow transplantation, which is considered the only cure and typically performed in patients under 16. Blood transfusions are also used, especially in severe anemia cases. Pain management is crucial to improve the quality of life for affected individuals.
Mindmap
Keywords
๐กSickle-cell disease
๐กHemoglobin S
๐กAutosomal incomplete dominance
๐กVaso-occlusion
๐กHemolysis
๐กHydroxyurea
๐กBone marrow transplantation
๐กSickle-cell trait
๐กMicrovascular trapping
๐กReticulocytes
Highlights
Sickle-cell disease is a group of hereditary blood disorders characterized by sickle-shaped red blood cells.
Sickle-cell disease is inherited in an incomplete autosomal dominant fashion, meaning even carriers with one allele can show mild symptoms.
Individuals homozygous for hemoglobin SS are fully affected by sickle-cell disease, with an estimated prevalence of 1 in 400 to 1 in 600 African Americans.
Carriers with one sickle-cell allele (heterozygous) are referred to as having sickle trait, which affects about 7-8% of African Americans.
The sickle-cell mutation appears to provide protection against malaria, explaining its persistence in populations where malaria is prevalent.
The disease is caused by a single point mutation at position 6 on the beta globin chain of hemoglobin, substituting glutamic acid with valine.
Deoxygenated hemoglobin S is less soluble than normal hemoglobin A, leading to red blood cell sickling during stress, hypoxia, or dehydration.
Sickled red blood cells can occlude small blood vessels, causing microvascular trapping and leading to severe complications like hemolysis and vaso-occlusion.
Sickled red blood cells have a dramatically shortened lifespan, living about 17 days compared to 120 days for normal red blood cells.
Patients with sickle-cell disease are at increased risk of infections, severe anemia, and complications from vaso-occlusion, such as stroke and acute chest syndrome.
Acute complications include infections, anemia, and vaso-occlusive crises, which can lead to severe pain, stroke, and other organ damage.
Chronic complications include hemolytic anemia, pain, neurologic deficits, renal hypertension, osteoporosis, and retinopathy.
Diagnostic methods include prenatal tests, newborn screenings, high-performance liquid chromatography, and hemoglobin electrophoresis.
Hydroxyurea is a common treatment that reduces pain episodes, hospitalizations, and prolongs survival in patients with sickle-cell disease.
Bone marrow or stem cell transplantation is the only potential cure for sickle-cell disease, typically performed in patients under 16 years old.
Transcripts
hey everyone and this is we're talking
about sickle-cell disease so what is
sickle-cell disease well is a group of
hereditary blood disorders with
characteristic sickle shaped red blood
cells so you can see here the cell on
the right is a sickle shaped red blood
cell and the one on the left is a normal
red blood cell now sickle cell disease
is inherited and is actually inherited
an incomplete autosomal dominant fashion
so on the right here in the schematic
you can see that an individual an
affected individual has two copies
they're homozygous so they have two
copies of the affected allele so they're
considered affected so in individuals
with only one allele are considered
unaffected carrier so it appears to be
recessive condition but in fact even
individuals with one of the affected
alleles can be can be affected to a very
slight degree so that's why we
considered incomplete autosomal dominant
so as I mentioned again an individual
with two copies of hemoglobin s s just
standing for the sickle cell disease
allele so he below man s s or homozygous
these are the affected these are the
individuals that are fully affected by
sickle cell disease and these homozygous
individuals make up about one one in
four hundred to one in six hundred
african-americans have or are homozygous
for sickle-cell disease and the other
portion of individuals the individuals
with only one affected allele are
considered heterozygous and they are
considered to have sickle trait so again
they're very slightly affected but not
as much to the degree as someone that
has homozygous hemoglobin s s and
individuals with the sick of trade over
heterozygous individuals about seven to
eight percent of African Americans have
sickle trade now the sickle cell
mutation appears to be protective
against malaria so that's the reason why
it seems to be pro our persistent
some of the populations where malaria is
prevalent so individuals with one allele
seems to be the best way to be able to
protected against malaria so what is
some of the pathophysiology of sickle
cell disease well it all has to do with
the hemoglobin beta globin chain so the
beta globin chain of hemoglobin is
affected and this beta globin chain is
encoded on chromosome 11 and in sickle
cell disease it's actually all due to an
amino acid substitution at position six
on the bladed globin chain and all it is
is a substitution from glutamic acid to
valine so there is only a single point
mutation changing glutamic acid to
valine at position six on the globe beta
globin chain and this is what causes the
deformed red blood cell shape the
problems in sickle cell disease are all
just due to a single point mutation and
what happens is when this beta globin
chain is mutated we considered
hemoglobin s and deoxygenated hemoglobin
s is less soluble than deoxygenated
hemoglobin a the normal hemoglobin so
that means that whenever Kim globin is
the option in Aidid for some reason it
can lead to increased polymerization so
that means that hemoglobin s can start
to aggregate in accumulate together it
leads to RBC sickling so deoxygenated
hemoglobin s can lead to RBC sickling
and the RBC sickling occurs during
conditions of stress and when red blood
cells do undergo sickling they can lead
to hemolysis and they can lead to
occlusion of the vasculature in these
individuals and you can think about it
if the red blood cells are traveling
through different
vasculature like capillaries for
instance if the cells are misshapen in
particular in a sickle shell shape they
may get clogged and they may get stuck
in certain areas in the vasculature this
is what leads to a lot of this occlusion
and a lot of symptoms related to sickle
cell disease and this is something we
call micro vascular trapping and all of
this leads to hemo phagocytosis so a lot
of times we'll get white blood cells
coming in and they will be essentially
cleaning up a lot of these red blood
cells a lot of these sickle red blood
cells and this leads to a dramatically
reduced lifespan of sick old red blood
cells and in fact it's about 17 days so
on average and normal red blood cell
lives for about 120 days but a sick old
red blood cell can live from anywhere
from 10 to 20 days usually about 17 days
so again it's because these red blood
cells become sickle they get clogged in
certain areas specifically in micro
vascular areas this can lead to an
inflammatory reaction white blood cells
can come in and start to phagocytize
these red blood cells and that's why you
see a dramatically reduced lifespan of
cycled red blood cells so what are some
of the signs and symptoms of sickle cell
disease well some of the acute
complications of sickle cell disease are
that individuals with sickle cell
disease are at an increased risk of
infections furthermore because of the
sickling of red blood cells these
patients can experience severe anemia
and again it's because of the sickling
of red blood cells and again signaling
of the red blood cells occurs during
conditions of stress so what are some of
those conditions of stress well they can
include fever they can include infection
they can include dehydration hypoxia and
acidosis
so anything that leads to a deoxidation
or further the oxygenation of hemoglobin
s Kenley
to sickling of the red blood cells which
can lead to complications so again these
individuals are at an increased risk of
infections and in fact affections can
lead to sickling so it's a vicious cycle
of sickling and symptoms of the red
blood cell cycling when the red blood
cells do undergo a sickling they can
lead to basal occlusion and a lot of
symptoms of sickle cell disease are due
to basal occlusion some of them include
acute basal occlusive pain so when a lot
of these sickle red blood cells get get
essentially trapped or occluded within
the vasculature it can cause pain it can
lead to stroke in some patients there
can be acute chest syndrome there can be
renal infarction myocardial infarction
priapism in venous thromboembolism so
anything that can lead to clogging up of
vasculature can lead to formation of
thrombi mbola emboli can lead to
infarction so essentially cutting off
the blood supply to certain areas like
the kidneys in the heart can all be due
to red blood cells being sickle and
essentially clogging up those arteries
or clogging up those vascular areas so
what are some of the chronic
complications of sickle cell disease
well essentially the biggest
complication is chronic compensated
hemolytic anemia so chronic compensated
chronic it's a long term process
compensated the body attempts to
compensate because of the chronicity of
the anemia and hemolytic anemia
hemolytic essentially means the body is
destroying the red blood cells and this
leads to these individuals essentially
having chronically low levels of
hemoglobin essentially it's a it's
usually these patients can have
hemoglobin levels from anywhere from 60
to 90 grams per liter the hematocrit is
usually low as well at about 20 to 30%
these patients when you look at a blood
smear the cells can have or the cells
can be polychromatic or have
polychromasia so when you look at them
they can be different colors so on a
blood smear you can see here's some
normal cells and you can see these other
cells that are different colors so
that's essentially what polychromasia
means these individuals can have
reticulocyte ptosis it's about 3 to 15%
of blood cells can be reticulocytes
reticulocytes are just immature red
blood cells so what happens it what is
when the body is destroying through that
hemophagocytic process you're destroying
those sick old red blood cells the body
compensates it starts to try to produce
more red blood cells and releases more
immature red blood cells that's why we
see increased levels of reticulocytes
and another thing you can see in a blood
smear is something called Howell Jolly
bodies and how jolly bodies are these
basal philic nuclear remnants inside a
red blood cell so you can see those as
well when you look at a blood smear in
other chronic complications include pain
usually from the basal occlusion there
can be neurologic deficits in some
patients pulmonary conditions due to
increased risk of infections there can
be renal hypertension osteoporosis
cardiomyopathy due to diastolic
dysfunction hepatic toxicity delayed
puberty reduced growth chronic leg
ulcers and proliferative retinopathy so
not all of these can occur in every
patient but some patients can have some
of these other complications some of
them are due to the basal occlusive
properties of sickle red blood cells so
pain again due to vaso occlusion due
because of pain individuals may not be
as active as other individuals so they
can have decreased bone mineral density
leading to an increased risk of
osteoporosis there can be again chronic
leg ulcers due to some of these basal
occlusive properties as well so how do
you diagnose sickle cell disease well
there's prenatal tests to deter
if a fetus carries sickle-cell alleles
there are newborn screenings to do the
same thing to see if a newborn infant is
carrying a mutated allele for
sickle-cell disease high performance
liquid chromatography can be performed
to assess and also haemoglobin
electrophoresis can be used to diagnose
sickle cell disease and usually it's
either with a cellulose acetate or
citrate agar gel and if you see more
than 30% hemoglobin s in these patients
then you can say okay these patients
most likely have sickle cell disease so
once we diagnose sickle cell disease how
do we treat it well one of the main
State treatments of sickle cell disease
is hydroxyurea hydroxyurea can reduce
episodes of acute pain it can reduce
hospitalization rates and can prolong
survival of patients with sickle cell
disease another possible treatment is
matoke we dick cell transplantation this
is thought to be usually thought to be
the only cure for sickle cell disease
and it's usually performed only in
individuals less than 16 years old and
blood transfusion can be performed in
patients with sickle cell disease
because especially in patients with
severe anemia if they have very low
hemoglobin and because of many of the
symptoms I've mentioned before due to
vaso occlusion and pain management is
very important in patients with sickle
cell disease as well anyways guys that
was a lesson on sickle cell disease I
hope you found this video helpful if you
did please like and subscribe for more
videos like this one and as always thank
you so much for watching and I'll see
you next time
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