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SICKLE CELL ANEMIA
(Hemoglobin Disorder)
Prepared by Lalruatdiki
Roll no-3, M.Sc 2nd Sem
Department of Biotechnology
History
•
In 1904, an African-American patient of Dr. James Herrick was
suffering from dizzy spells, open sores on his leg...
DEFINITION
• Sickle cell disease(SCD):is a hereditary blood disorder, characterized by an
abnormality in the oxygen-carryi...
Structure of hemoglobin
What causes sickle cell anemia?
• Caused by abnormal hemoglobin called sickle hemoglobin or
hemoglobin S as a result of ge...
Molecular Basis of Disease
• Normally, humans have hemoglobin A,
alpha chain=141 amino acids long.
beta chain=146 amino ac...
Mutation on chromosome No 11
Mutation
• The sickle-shaped red blood cells break apart easily causing anemia.
• Hemoglobin S with this mutation is referred to as...
Oxygen’s functional imbalance and the changes in the
RBC membrane
• Under deoxygenation condition, hemoglobin S polymerize...
Sickling consequences
The sickled red cells with membrane alterations impair blood flow
causing vascular occlusion.
It c...
Pathophysiology
Deoxygenation
polymerization of
hemoglobin
sickling of red cells
endothelial
damage/activation
RBC and leu...
Genetic cross
• Children are born with sickle cell disease; it is not
contagious.
• Occurs when a person inherits two abno...
• If one parent has sickle-cell anemia and the other has sickle cell
trait, then the child has a 50% chance of having sick...
• When both parents have sickle-cell trait, a child has a 25% chance of sickle-
cell disease, 25% do not carry any sickle-...
Effects at the protein level
Normal hemoglobin (left) and hemoglobin
in sickled red blood cells (right) look
different; th...
• There are effects at the cellular level: when red blood cells carrying
mutant hemoglobin are deprived of oxygen, acidosi...
References
1. Biotechnology, a problem approach by
Pranav Kumar, Usha Mina.
2. Theoretical genetics, stephen taylor.
3. He...
Sickle cell anemia
Sickle cell anemia
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Sickle cell anemia

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Sickle cell anemia

  1. 1. SICKLE CELL ANEMIA (Hemoglobin Disorder) Prepared by Lalruatdiki Roll no-3, M.Sc 2nd Sem Department of Biotechnology
  2. 2. History • In 1904, an African-American patient of Dr. James Herrick was suffering from dizzy spells, open sores on his legs, and weakness. A blood sample was taken of the patient and studied under the microscope. Dr. Herrick noticed a problem with his patient's red blood cells. The red blood cells were bent and twisted into crescent shapes that reminded the doctor of a sickle, a tool that was used by farmers to cut grain before modern-day farm equipment. In fact, this is where the disease got its name. Dr. Herrick is given credit for the discovery of this disease and the name by which we know it today--sickle-cell anemia. He was the first to say that the sickle shape of his patient's red blood cells was causing the weakness, dizzy spells, and sores on his patient's legs.
  3. 3. DEFINITION • Sickle cell disease(SCD):is a hereditary blood disorder, characterized by an abnormality in the oxygen-carrying haemoglobin molecule in red blood cells. • This leads to a propensity for the cells to assume an abnormal, rigid, sickle- like shape under certain circumstances. • Sickle-cell disease is associated with a number of acute and chronic health problems, such as severe infections, attacks of severe pain ("sickle-cell crisis"), and stroke, and there is an increased risk of death. • more common in the US among the African American population, and around the world, it usually happens among populations originating in tropical areas.  Red bood cells contain an iron rich protein called hemoglobin that carries oxygen from lungs to the rest of the body. Normal cells are disc shaped, flexible and look like donuts without holes in the center which enables them to travel through small blood vessels to deliver oxygen to all parts of the body.
  4. 4. Structure of hemoglobin
  5. 5. What causes sickle cell anemia? • Caused by abnormal hemoglobin called sickle hemoglobin or hemoglobin S as a result of genetic mutation (missense mutation) in the gene for hemoglobin, which results in the production of sickle hemoglobin. • Causes red blood cells to develop a sickle, or crescent shape.
  6. 6. Molecular Basis of Disease • Normally, humans have hemoglobin A, alpha chain=141 amino acids long. beta chain=146 amino acids long. • The sickle-cell disease occurs when the 6th amino acid, glutamic acid (hydof the beta chain, is replaced by valine to change its structure and function. • Mutation is a single nucleotide substitution on chromosome 11. • GAG  GTG results in substitution of valine (negatively charged) for glutamate (non polar) • Mutant hemoglobin polymerizes under low oxygen conditions, it sticks together and form bundles of long rods that distort red cells into the classic sickle shape. • Sickle cells are stiff and sticky. They tend to block blood flow in the blood vessels of the limbs and organs. And therefore can cause pain and organ damage.
  7. 7. Mutation on chromosome No 11 Mutation
  8. 8. • The sickle-shaped red blood cells break apart easily causing anemia. • Hemoglobin S with this mutation is referred to as HbS as opposed to the normal adult HbA. Effects at the DNA level
  9. 9. Oxygen’s functional imbalance and the changes in the RBC membrane • Under deoxygenation condition, hemoglobin S polymerized to form sickle cell. • Prevents the use of oxygen by hemoglobin S. • Free oxygen combine to form molecular oxygen. • Free electrons are incorporated by the oxygen molecule. • Activated species of oxygen superoxide anions. • Superoxide anions attack the membrane. Destruction of fat acids by the superoxide anions and formed membrane lesions. • The activated oxygen also oxidizes the hemoglobin S molecule turning it into meta HbS. • The meta HbS get together forming Heinz Bodies towards the membrane, alters the Band 3 protein and the phosphatidylserine arrangement in the membrane leading to exposition of membrane.
  10. 10. Sickling consequences The sickled red cells with membrane alterations impair blood flow causing vascular occlusion. It causes tissue swelling and pain in the hands and feet. It also causes hemolysis. Sickle RBC live for 10-20 days instead of the normal 120 days. So people with this disorder often have low red blood cell counts (anemia), which is why this disease is commonly referred to as sickle cell anemia. The sickled red cells are phagocytised by macrophage. Macrophage activated by phagocytosis, released cytokines and diffuse to the microvessels of the central nervous system sending signals that cause vaso constriction i.e increase heart rate and blood pressure, metabolic disturbances, fever, pain.
  11. 11. Pathophysiology Deoxygenation polymerization of hemoglobin sickling of red cells endothelial damage/activation RBC and leukocyte adhesion to endothelium, vasoconstriction vascular occlusion, organ ischemia and end-organ damage
  12. 12. Genetic cross • Children are born with sickle cell disease; it is not contagious. • Occurs when a person inherits two abnormal copies of the hemoglobin gene , one from each parent. • A person with a single abnormal copy does not experience symptoms and is said to have sickle cell trait. Such people are referred to as carriers.
  13. 13. • If one parent has sickle-cell anemia and the other has sickle cell trait, then the child has a 50% chance of having sickle cell disease and 50% chance of having sickle-cell trait.
  14. 14. • 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.
  15. 15. Effects at the protein level Normal hemoglobin (left) and hemoglobin in sickled red blood cells (right) look different; the mutation in the DNA slightly changes the shape of the hemoglobin molecule, allowing it to clump together.
  16. 16. • There are effects at the cellular level: when red blood cells carrying mutant hemoglobin are deprived of oxygen, acidosis, dehydration, hypoxia, they become sickle-shaped instead of the usual round shape. This shape can sometimes interrupt blood flow. • There are negative effects at the whole organism level: under conditions such as high elevation and intense exercise, a carrier of the sickle cell allele may occasionally show symptoms such as pain and fatique. • There are positive effects at the whole organism level: Carriers of the sickle cell allele are resistant to malaria, The reason is that in tropical areas there is also a high incidence of malaria, a parasitic disease caused by the bug Plasmodium falciparium, which is carried by the Anopheles mosquitoe. In one of the stages of the life of the parasite, it depends on the red cell (actually, on hemoglobin) to survive.
  17. 17. References 1. Biotechnology, a problem approach by Pranav Kumar, Usha Mina. 2. Theoretical genetics, stephen taylor. 3. Hemoglobin and its defects, Info Biochemistry 4. Understanding evolution; “a case study on sickle cell anemia”.

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