Thalassemia, sickle cell anemia

1. THALASSEMIA &
SICKLE CELL ANAEMIA
1ST YEAR MBBS
BIOCHEMISTRY

2. REVISION QUESTIONS
• What is the site of ETC ?
• Mitochondria is also known as ______
• How many ATP are produce by NADH ?
• Complex I is also called_______
• Inhibitors of ETC acting on FMN ?

3. NORMAL HAEMOGLOBIN
• Hemoglobin is the major
constituent of the red blood
cell
• It is comprised of heme and
globin.
• The major (96%) type of
hemoglobin present in adults
is called HbA
• It has 2 alpha globin chains
and 2 beta globin chains
(α2β2).

4. Abnormal
Haemoglobin
(Hemoglobinopathy)
Thalassemia
Sickle Cell
Anaemia

5. THALASSEMIA - DEFINITION
• Thalassemia is an inherited blood disorder in which the body
produces an abnormal form of hemoglobin
• This results in excessive destruction of red blood cells and anemia
• TYPES OF THALASSEMIA:
- Alpha thalassemia
- Beta thalassemia

6. PATHOPHYSIOLOGY
• Genes are responsible for regulating the
synthesis and structure of different globins which
are divided into 2 groups
1. Chromosome 16 : Alpha globin genes
2. Chromosome 11 : Gamma , Delta and Beta globin
genes

7. 90% 5%
2%
Less than
1%
ALPHA
ZETA EPSILON GAMMA DELTA
BETA

8. NORMALLY : 2 ALPHA + 2
BETA CHAINS

9. ALPHA THALASSEMIA IS THE RESULT OF
CHANGES IN THE GENES FOR THE ALPHA
GLOBIN COMPONENT OF HEMOGLOBIN
Normal Alpha thalassemia

10. TYPES OF ALPHA THALASSEMIA
1. Silent carrier : (α α / - α)
- Loss of one of the 4 alpha globulin genes
- No physical manifestation
2. Thalassemia trait : (α α / - -) OR (α - / - α)
- A loss of two of the four alpha-globin genes
- Minor anaemia
3. Hemoglobin H disease: (α - / - -)
- A loss of three of the four alpha-globin genes
- Moderate anaemia
4. Hydrops Fetalis: (- - / - -)
- Lacks all four alpha-globin genes
- Severe form not compatible will life

11. SYMPTOMS OF ALPHA
THALASSEMIA

12. BETA THALASSEMIA
• When the body has a problem producing beta
globin is called Beta Thassemia
• Can be mild to severe

13. BetaThalassemia
Thalassemia Major
(Cooleys anemia)
- severe form
- two abnormal genes that
cause either a severe decrease
or complete lack of
Beta globulin chain
Thalassemia Minor
- presence of one normal gene
& one with a mutation
- Mild to moderate anaemia

15. SICKLE CELL DISEASE
• Sickle cell disease (SCD) is a group of
inherited red blood cell disorder
• Healthy red blood cells are round and they
move through small blood vessels carrying
oxygen to all parts of the body
• In sickle cell disease ,the red blood cells
become hard and sticky and look like a C-
shaped farm tool called a sickle.

17. • Sickle cells die early , which causes a constant
shortage of red blood cells
• Sickle cells can get stuck in small blood
vessels & block the flow of blood & oxygen to
organs in the body
• These blockages cause repeated episodes of
severe pain , organ damage, serious infections
, even stroke

18. MUTATION
• Caused by mutation
in beta globin gene –
at sixth position ,
glutamic acid is
replaced by valine
• Haemoglobin S (HbS)
• Red blood cells
typically live 90-120
days , but sickle cells
only survive 10 - 20
days

19. Mechanism of sickling in
Sickle Cell Anaemia

20. QUESTION
• Can patients with Sickle cell disease have
malaria
• ANSWER:
1. The malaria parasites grow within the RBC. As
sickling starts the damaged RBC would be
removed by macrophages along with the
parasite
2. Life span of RBC is also reduced in sickle cell
anemia

21. DIAGNOSIS
• Peripheral smear
• Hb electrophorosis
• Sickling test Principle :
- Sodium meta bisulphite reduces the
oxygen tension inducing the typical
sickle – shape of red blood cells.
- Sample: Fresh blood in any
anticoagulant.
- Method: mix 1 drop of blood with 1 drop
of 2% sodium meta bisulphate solution
on a microscope slide.

22. MICROSCOPY

23. THANK YOU