BHS 170

PHYSIOLOGY I
TITLE: SICKLE CELL ANEMIA

NAME : IFFAHTUL AMIRAH BINTI ABDULLAH

: ADLYN SHAHEERA BINTI AHMAD SHAHIZI

DATE :

LECTURER: MARLINA MOHD MYDIN

 The explanation of sickle cell anaemia or sickle cell disease is a refers to the group of
hemoglobinopathies is genetic disorders mainly affecting the structure or production of the hemoglobin
molecule. The structure changed caused by a mutation in the hemoglobin beta chain (Adebiyi MG and
Manalo JM et al., 2019 ). Hemoglobin made up of four peptide chain each bound to heme group and
different hemoglobin has different combination of this chains like hemoglobin A (HbA) made up of two
alpha globin (α-globin) and two beta globin (β-globin) which primary hemoglobin affected in sickle cell.
Specifically, the beta globin (β-globin) chains end up misshapen. This is because of a mutation in the beta
globin gene or HBB gene.The mutation of beta globin caused by mutation level called base substitution.
Base substitution involved swapping of one nucleotide for another during DNA replication as resulting in
the 6th acid amino of beta globin being valine instead of glutamic acid that lead to significant function
changes in protein function also knows as non conservative missense mutation. All together would form a
hemoglobin tethamer with two a-globin and two mutated beta globin protien called sickle hemoglobin
( HbS ) that carried perfectly oxygen. Nevertheless,the sickling process take place in the HbS that change
in shapes in sickle when deoxygenated happen that allows generate other HbS protein and form long
polymers that distorts the red blood cell into crescent. Otherwise, the replication in red blood cell being
the valline impart a sticky adhesive quality and resulting in sickling likely change the shape and structure
being abnormal red blood cell whereas glutamic acid which negatively charge amino acid and thus
prevents red blood cell from sickling.

.
 Inherited disease like sickle cell owing to sickle cell trait “carrier”. The sickle cell trait population
beginning started African-American about 3 million people especially black-american also among
ancestor come from sub-saharan African which estimated that there are 300 million people with sickle
cell trait and one-third of this number ( El Ariss AB, Younes M, Matar J, et.al 2016 ). Gibson and
colleague mentions that the prevalence is as high as 25% in some part of Africa and 60% in Saudi Arabia
( Gibson JS, Rees DC, 2016 ) . Because of the high migration of people from areas of high prevalence
like Africa, Middle East, the prevalence of both sickle cell trait and disease will increase in the western
part of the world. Hence, there are the difference between sickle cell trait and anemia despite the fact both
can exposed the disease. Sickle cell carrier or trait is said to have a sickle cell minor condition in which
the individual possesses recessive allele of gene mutation of sickle cell trait but the individual does not
show any symptoms or develop of the disease. Detection of sickle cell can only be confirmed by a blood
test.In those with sickle cell trait, red blood cells, at rest, are normal appearing when viewed under the
microscope. A sickle cell carrier patient is said to have sickle cell major when the individual has both the
recessive alleles.. If one parent has sickle cell anaemia and the other has sickle cell trait, then the child has
a 50% chance of having sickle cell disease and a 50% chance of having sickle cell trait. When both
parents have sickle cell trait, a child has a 25% chance of sickle cell disease; 25% do not carry any sickle
cell alleles, and 50% have the heterozygous condition ( Spatz MA. 2017 ). Alongside with sickle cell
disease there are other types of sickle cell disease like HbSS , HbS and HbS beta thalassemia.HbSS is the
most common called sickle cell anemia and usuallly the most severe fprm of the disease. Second HbSC
types are inherit a hemoglobbin “ S” gene from one parent and gene for a different type of abnormal
vcalled “ C” from the other parent. This usually a milder form of SCD .HbS beta thalassmia isother type
abnormality from the other parent which usus]ally “zero” ( HbS betaͦ ) and “ plus “ ( HbS beta +)Those
with HbS beta0-thalassemia usually have a severe form of SCD. People with HbS beta+-thalassemia tend
to have a milder form of SCD.
 Moreover, the complication due sickle cell disease or anemia lead to a lot many symptom of health
because origin function have been affected started from early childhood. Sickle cell disease may lead to
loss of red blood elasticity Is central. The difference of normal red blood cell are quiet elastic and in
shape round, smooth and concave and the benefits of this that its allows them to easily squeeze through a
vessel and carry amount oxygen through body. On the other hand, the existence of Sickle cell anaemia
form shape which isn’t very vessel friendly and going stick together so well that an cause circulation
problem and made up low oxygen tension because of delicate and rupture lifespan of red blood cell is
short.Beside, the repeated episode of sickling damage the cell membrane and decrease the cell’s
elasticity.As a conclusion, these rigid blood cells are unable to deform as they pass through narrow
capillaries,leading to vessels occlusion.In spite of the fact that, the bone narrow attempts to compensate
by creating new re blood cells, it does not much the rate of destruction. Healthy blood cells typically
function for 90-120 days, but sickled cells only last 10-20 days. Beside, the sickle blood cell causes
constant shortage of red blood cell till they travel around through blood vessel and get stucked and clog
the blood flow.This causes pain and other seriuos complication which helath problems such as infection,
acute chest syndrome and stroke. Due the fact, stroke is the mainly complication happen from progressive
narrowing of blood vessel, prevents oxygen from reaching the brain. Silent stroke is probably five times
as common as symptomatic stroke. About 10-15% of children with SCD have strokes, with silent strokes
predominating in younger patients. ( Adams RJ, Ohene-Frempong K, Wang W , 2001 ).
 Furthermore, the complication start presentig in early infant mainly for their growth due to the sickle
cell anemia mainly leads to too few red blow because they break down faster than normal red blood cell.
Hence, early children could be effected in growth which have delayed growth and delayed puberty due to
low tension production of red blood cell. Red blood cell needs oxygen and nutrient to delivered to the
body tissues for growth. Also, toward time chest syndrome for kids could be effected. This is caused
by inflammation, infection, an blocked small blood vessels of the lung. Signs include chest pain,
coughing, trouble breathing, and fever. Beside, the causes in Pulmonary hypertension (increased pressure
on the pulmonary artery) can lead to strain on the right ventricle and a risk of heart failure; typical
symptoms are shortness of breath, decreased exercise tolerance, and episodes of syncope. 21% of children
and 30% of adults have evidence of pulmonary hypertension when tested; this is associated with reduced
walking distance and increased mortality ( Caughey MC, Poole C, Ataga KI, Hinderliter AL 2015 ). In
any other cases, the presenting as early as six months of age, and may occur in children with sickle cell
trait manifestations with dactylitis can last up in a month as their protective fetal hemoglobin, HbF, is
replaced with adult hemoglobin and the disease manifests and is very often the presenting sign of the
disorder.

Along with that, patient with SDC occurring condition known as “ sickle cell crisis” which results
anemia and crises that could be of many types including the vaso-occlusive crisis, aplastic crisis, splenic
sequestration crisis, haemolytic crisis, and others. Most episodes of sickle cell crises last between five and
seven days. "Although infection, dehydration, and acidosis (all of which favor sickling) can act as
triggers, in most instances, no predisposing cause is identified." Splenic sequestration crisis are acute and
painful, the spleen enlargement caused by in traspenic trapping of red blood cell as consideration an
emergency. Other than that, aplastic crisis are normally triggered by production which infection almost
completely prevent production causes the shortened red cell life span of sickle cell anemia patient results
pale appearance, fast heart rate and fatigue.

Chronic complication in Sickle cell disease also can causes iron overload which is common due to
repeated transfusions and chronic hemolysis by contains 200 to 250mg of iron in packed red blood cells.
Excessive iron mainly affected the heart, lungs and endocrine gland. The best way to treatment iron
overload by transfusion practise in follow the rule of having hemoglobin close to 70 mg/dL. Beside
choosing transfusion over simple transfusion also helps reducing.
 As we know, the sickle cell anemia are inherited disease cause gene mutation are can be cure by
counselor or medical check up for primary consciousnesses of these disease in psychologies therapies
that aim current medical treatment and advice for planning and determine for living normal life and
planning future life specially married . Due to mainly causes of sickle cell anemia stroke . Hence, there
are stroke prevention which is Transcranial Doppler ultrasound ( TCD ) can detect children with sickle
cell that have high risk for stroke especially for children. The ultrasound test detects blood vessels
partially obstructed by sickle cell by measuring the rate of blood into the brain, as blood flow velocity is
inversely related to arterial diameter, high blood-flow velocity is correlated with narrowing of the
arteries.Beside, the prevention also include blood transfusion that prevent complications by decreasing
the number of red blood cell that can sickle by adding the normal red blood cell which also helps reduce
risk of silent stroke and first stroke . For the effectiveness and and painless treatment could use
hydroxyurea which approved drug for the treatment of sickle cell anemia and was shown to decrease the
number and severity of attacks in 1995. Hydroxyurea reactivating fetal haemoglobin production in place
of the haemoglobin S that causes sickle cell anaemia. Hydroxyurea had previously been used as
a chemotherapy agent, and some concern exists that long-term use may be harmful, but this risk is either
absent or very small and the benefits likely outweigh the risks ( Yawn BP, Buchanan GR, Afenyi-Annan
AN, Ballas SK, et al 2014 ). However, promising new medications are intervening in tons of ways, like
keeping oxygen bonded to hemoglobin to prevent sickling or reducing the stickiness of sickled cells.
Moreover, the ability to edit DNA has raise the possibility of enabling stem cells to produce normal
hemoglobin.

The answer of sickle cell anemia can reverted only for bone narrow and stem cell transplant due to
both of them reproduce red blood cell a spongy tissue found in the centre of some bones .They can
turn into different types of blood cells . The donor are given through a drip into vein to reproduced the
sicle cell.Currently, only full siblings whose bone marrow closely matches can donate stem cell
cells for transplant in sickle cell disease . However, due to the high level of danger involved, like graft
versus host disease, life threatening problem where the transplant performed started to attack to other cell
in your body and risk for infection or bleeding. Infection or bleeding may be severe and, in rare cases,
may cause death.
 The conclusion of elaboration in sickle cell anemia already explain within definition , causes and cure
to give awareness for premature treatment in sickle cell disease. The fact of this disease causes by gene
mutation would give more attention in studies of gene counseling would help investigating individual or
families history about genetic disorders for management towards future for available option. Beside, its
our responsibility for our health to take care by knowledgeable through our health condition and health
history by regular check up for reducing risk of getting critical disease and come up of solution in order to
improve health also increase lifespan for wellness life . In other hand, the gene consultation alsoprovide
for disscusion for treatment in how to live life in adaption as patient sickle cell anemia.
REFERENCE

1. Sickle Cell Anemia definition

Mayo clinic

https://www.mayoclinic.org/diseases-conditions/sickle-cell-anemia/symptoms-causes/syc-20355876

Sickle cell anemia ncbi

https://www.ncbi.nlm.nih.gov/books/NBK482164/

2. Sickle cell trait

Sickle cell trait ncbi

https://www.ncbi.nlm.nih.gov/books/NBK537130/

Centers for disease control and prevention ( CDC )

https://www.cdc.gov/ncbddd/sicklecell/traits.html

3. Sickle cell anemia symptoms and treatment

Sickle cell anemia ncbi

https://www.ncbi.nlm.nih.gov/books/NBK482164/

Texas’s children Hospitals

https://www.texaschildrens.org/health/bone-marrow-transplantation-children-sickle-cell-disease