Submitted By: Aneeqa

Mohsin
Roll number:
18BsZOL28757
Programme: - Bs Zoology
Seminar topic:-
SICKLE CELL ANEMIA
 Sickle cell Anemia
CONTENTS:-
 History
 Definition
 Structure
 Types
 Causes
 Risk factors
 Molecular Basis of Disease
 Effects
 Symptoms
 Complications
 Pregnancy and sickle cell Anemia
 Diagnosis
 Treatment
 Home care

History:
 Sickle cell anemia is one of a group of disorders known as sickle cell disease. Sickle cell
anemia is an inherited red blood cell disorder in which there is not enough healthy red blood
cells to carry oxygen throughout your body.
Normally, the flexible, round red blood cells move easily through blood vessels. In sickle cell
anemia, the red blood cells are shaped like sickles or crescent moons. These rigid, sticky cells
can get stuck in small blood vessels which can slow or block blood flow and oxygen to parts of
the body.
There is no cure for most people with sickle cell anemia. But treatments can relieve pain and
help prevent complications associated with the disease.

Patterns of inheritance

Autosomal recessive disorder

 It is present as single gene disorder.
 The characteristic of autosomal recessive disorder are as following;
1. Trait is only visible in siblings but not in parents or other relatives
2. Parents of affected person may have blood relatives Hi
3. ¼th of children of such parents are affected reappearance risk at each birth is 25%.
4. Both male and female children have equal chance of affected.
Definition:-

‘’A hereditary blood disorder characterized by abnormalities in oxygen carrying hemoglobin

molecule in red blood cells is called Sickle cell Anemia.’’
Or
‘’An iron rich protein that carry oxygen from lungs to rest of the body is called hemoglobin.’’

Structure:
There are three types of structure

1. Normal Red blood cells

 Its shape is rounded.
 It is very flexible.
2. Sickle Shape Red blood cells
 These have crescent shape.
 It is Stiff and sticky.

3. Hemoglobin:

The hemoglobin (Hb) molecule is roughly spherical and comprises of

Two pairs of dissimilar subunits

 Each of the subunits is a folded polypeptide chain (the globin Portion) with a heme group
(derived from porphyrin) attached.
  It contains two polypeptide chains.
 One chain contain two alpha hemoglobin chain (141 Amino acid)
 The second chain contain two beta hemoglobin chain (146 Amino acid).
o At the center of each heme group is a single atom of iron in the Ferrous (Fe2+)State.

Thus heme is a metallo-porphyrin incidentally responsible for the red color of blood.

 Diagrammatic structure of oxygenated hemoglobin

(HbA)
The oxygen-binding site of Hb is the heme pocket present in each of the four polypeptide chains;
a Single atom of oxygen forms a reversible bond with the ferrous iron at each of these sites, so a
molecule of Hb binds four oxygen molecules; the product is oxyhemoglobin (O2Hb).

Oxygen delivery function of Hb; that is its ability to “pick up” oxygen at the lungs and
“release” it to tissue cells is made possible by minute conformational changes in quaternary
structure that occur in the hemoglobin molecule and which alter the affinity of the Heme pocket
for oxygen.

Hb has two quaternary structural states:

The deoxy state (low oxygen affinity) and the oxy state (high Oxygen affinity).

A range of environmental factors determine the quaternary state of Hb and therefore its relative
oxygen affinity. The microenvironment in the lungs favors the oxy-quaternary state, and thus Hb
has high affinity for oxygen here.

By contrast, the microenvironment of the tissues induces the Conformational change in Hb

structure that reduces its affinity for oxygen, thus allowing oxygen to be released to tissue cells.
  Types :
Hemoglobin has two alpha chains and two beta polypeptide chains. The
four main types of sickle cell anemia are caused by different mutations in these genes.

 Hemoglobin SS disease:

It is the most common type of sickle cell disease. It occurs when you
inherit copies of the hemoglobin S gene from both parents. This forms hemoglobin known as
Hb SS. As the most severe form of SCD, individuals with this form also experience the worst
symptoms at a higher rate.

 Hemoglobin SC disease

Hemoglobin SC disease is the second most common type of sickle cell disease. It occurs
when you inherit the Hb C gene from one parent and the Hb S gene from the other.
Individuals with Hb SC have similar symptoms to individuals with Hb SS. However, the
anemia is less severe.
  Hemoglobin SB+ (beta) thalassemia

Hemoglobin SB+ (beta) thalassemia affects beta globin gene production. The size of the red
blood cell is reduced because less beta protein is made. If inherited with the Hb S gene, you
will have hemoglobin S beta thalassemia. Symptoms are not as severe.

 Hemoglobin SB 0 (Beta-zero) thalassemia:

Sickle beta-zero thalassemia is the fourth type of sickle cell disease. It also involves the beta
globin gene. It has similar symptoms to Hb SS anemia. However, sometimes the symptoms
of beta zero thalassemia are more severe. It is associated with a poorer prognosis.

 Hemoglobin SD, hemoglobin SE, and hemoglobin SO

These types of sickle cell disease are more rare and usually don’t have severe symptoms

Causes:
 By defection or mutation in gene.
 It may be inherited from parents.
 Physical or physiological stress
 Alcohol
 Low oxygen tension

Risk factors:
In the United States, most people who have sickle cell disease are of African ancestry or
identify themselves as Black.

 About 1 in 13 Black or African American babies is born with sickle cell trait.
 About 1 in every 365 Black or African American babies is born with sickle cell disease.

There are also many people who have sickle cell disease who come from Hispanic, southern
European, Middle Eastern, or Asian Indian backgrounds.

About 100,000 Americans have sickle cell disease.

Molecular Basis of Disease:

  At the molecular level, the exchange of amino acids cause an imbalance because of the
loss of negative charges of HbS in relation to HbA
 Sickle cell hemoglobin (HbS) results from a single base-pair mutation of the two β
subunits in normal hemoglobin (HbA). An adenine-to-thymine substitution in the sixth
codon replaces glutamic acid with valine in the sixth amino acid position.
 On Chromosomes 11 single nucleotide substitution GAG to GAT; cause RBCs to
develop sickle shape.

Effects on DNA Level

Normal Sickle cell

DNA. GAG. GTG

RNA. GAG GTG

Protein GLU VAL

Symptoms:
 Signs and symptoms of sickle cell anemia usually appear around 5 months of age.
They vary from person to person and change over time. Signs and symptoms can include:

 Anemia: Sickle cells break apart easily and die, leaving you with too few red blood cells.
Red blood cells usually live for about 120 days before they need to be replaced. But sickle
cells usually die in 10 to 20 days, leaving a shortage of red blood cells (anemia).

Without enough red blood cells, your body can't get enough oxygen, causing fatigue.

 Episodes of pain. Periodic episodes of pain, called pain crises, are a major symptom of
sickle cell anemia. Pain develops when sickle-shaped red blood cells block blood flow
through tiny blood vessels to your chest, abdomen and joints. Pain can also occur in your
bones.

The pain varies in intensity and can last for a few hours to a few weeks. Some people have
only a few pain crises a year. Others have a dozen or more pain crises a year. A severe pain
crisis requires a hospital stay.

Some adolescents and adults with sickle cell anemia also have chronic pain, which can
result from bone and joint damage, ulcers, and other causes.

 Swelling of hands and feet: The swelling is caused by sickle-shaped red blood cells
blocking blood flow to the hands and feet.

 Frequent infections: Sickle cells can damage your spleen, leaving you more vulnerable
to infections. Doctors commonly give infants and children with sickle cell anemia
vaccinations and antibiotics to prevent potentially life-threatening infections, such as
pneumonia.

 Delayed growth or puberty: Red blood cells provide your body with the oxygen and
nutrients needed for growth. A shortage of healthy red blood cells can slow growth in
infants and children and delay puberty in teenagers.

 Vision problems: Tiny blood vessels that supply your eyes can become plugged with
sickle cells. This can damage the retina — the portion of the eye that processes visual
images — and leads to vision problems.
Complications:

Sickle cell anemia can lead to a host of complications, including:

 Stroke. Sickle cells can block blood flow to an area of your brain. Signs of stroke include
seizures, weakness or numbness of your arms and legs, sudden speech difficulties, and loss
of consciousness. If your child has any of these signs and symptoms, seek medical
treatment immediately. A stroke can be fatal.

 Acute chest syndrome. A lung infection or sickle cells blocking blood vessels in your
lungs can cause this life-threatening complication, resulting in chest pain, fever and
difficulty breathing. It might require emergency medical treatment.

 Pulmonary hypertension. People with sickle cell anemia can develop high blood
pressure in their lungs. This complication usually affects adults. Shortness of breath and
fatigue are common symptoms of this condition, which can be fatal.

 Organ damage. Sickle cells that block blood flow to organs deprive the affected organs
of blood and oxygen. In sickle cell anemia, blood is also chronically low in oxygen. This
lack of oxygen-rich blood can damage nerves and organs, including your kidneys, liver and
spleen, and can be fatal.

 Blindness. Sickle cells can block tiny blood vessels that supply your eyes. Over time, this
can damage your eye and lead to blindness.

 Leg ulcers. Sickle cell anemia can cause open sores on your legs.

 Gallstones. The breakdown of red blood cells produces a substance called bilirubin. A
high level of bilirubin in your body can lead to gallstones.

 Priapism. In this condition, men with sickle cell anemia can have painful, long-lasting
erections. Sickle cells can block the blood vessels in the penis, which can lead to impotence
over time.

Pregnancy and sickle cell disease

 Pregnant women who have sickle cell disease are at greater risk for problems. If you are
pregnant or planning for pregnancy, meet with a doctor who specializes in high-risk pregnancies
and has experience with patients who have sickle cell disease.

Your doctor may prescribe certain vitamins and will be careful to prescribe pain medicines that
are safe for you and your baby. You should not use hydroxyurea during pregnancy.

You may need to have one or more blood transfusions during pregnancy to treat problems, such
as anemia symptoms that get worse. You may also experience more pain crises or be at higher
risk of having acute chest syndrome. Your doctor will talk to you about how to help prevent
these complications.

Diagnosis

All newborns in the United States are screened for sickle cell disease. Prebirth testing looks for
the sickle cell gene in your amniotic fluid.

In children and adults, one or more of the following procedures may also be used to diagnose
sickle cell disease.

Hb electrophoresis:

Hb electrophoresis is always needed to confirm the diagnosis of sickle cell disease. It measures
the different types of hemoglobin in the blood.

Blood tests: Several blood tests can be used to look for SCD:

 Blood counts can reveal an abnormal Hb level in the range of 6 to 8 grams per deciliter.

 Blood films may show RBCs that appear as irregularly contracted cells.

 Sickle solubility tests look for the presence of Hb S.

Treatment: A number of different treatments are available for SCD:

 Rehydration with intravenous fluids helps red blood cells return to a normal state. The
red blood cells are more likely to deform and assume the sickle shape if you’re
dehydration.
 Treating underlying or associated infections is an important part of managing the crisis,
as the stress of an infection can result in a sickle cell crisis. An infection may also result
as a complication of a crisis.
 Blood transfusions improve transport of oxygen and nutrients as needed. Packed red cells
are removed from donated blood and given to patients.
 Supplemental oxygen is given through a mask. It makes breathing easier and improves
oxygen levels in the blood.
 Pain medication is used to relieve the pain during a sickle crisis. You may need over-the-
counter drugs or strong prescription pain medication like morphine, Droxia, Hydrea)
helps to increase production of fetal hemoglobin. It may reduce the number of blood
transfusions.
 Immunizations can help prevent infections. Patients tend to have lower immunity.
 Bone marrow transplant has been used to treat sickle cell anemia. Children younger than
16 years of age who have severe complications and have a matching donor are the best
candidates.