hemoglobinopathies and electrophoresis

Question 1

list def and types of qualitative hemoglobinopathy .

Answer 1

-def : abnormality in primary structure of globin
-types :
Hb S ( sickle cell anemia )
Hb C
Hb SC
Hb M ( met Hb )

Question 2

Hb S is …….

Answer 2

autosomal recessive disorder

Question 3

what’s the nature of this lesion ( Hb S ) ?

Answer 3

-substitution of glutamate at position 6 in the β chain by valine ( point mutation )
- life span of RBCs is less than 20 days

Question 4

list types of Hb S

Answer 4

1. Heterozygous individuals ( sickle cell trait ) :
   50% Hb S & 50% normal Hb with mild condition
2. homozygous ( sickle cell disease ) :
   received gene defect from both parents

Question 5

what’s the adv of sickle cell trait

Answer 5

resistant to the malarial infection as the short life span can’t support the parasite

Question 6

symptoms of sickle cell trait present only in ……..

Answer 6

hypoxic condition

Question 7

in sickle cell disease , sickling cause tissue …….

Answer 7

anoxia

Question 8

illustrate nature of that lesion ( sickle cell disease)

Answer 8

sickling cause tissue anoxia : valine form protrusion on β globin that fit to other β globin and make long filaments that block the flow of the blood .
sickled cells occlude small vessels lead to localized anoxia then pain then infarction

Question 9

during the electrophoresis the S migrate ……..toward anode

Answer 9

more slowly

Question 10

illustrate how sickle cell anemia cause microvascular occlusion .

Answer 10

• the mean diameter of RBCs is 7.5 μm whereas that of the microvasculature is 3-4 μm
• compared to normal RBCs , sickled cells have a dec ability to deform and an inc tendancy to adhere to the vessel wall
• this makes moving through small vessels difficult , thereby causing microvascular occlusion.

Question 11

the severity of the sickling inc by …….

Answer 11

any variable that inc the proportion of HbS in the deoxy state ( that is reduces the oxygen affinity of HbS )

Question 12

what’s the ttt of sickle cell anemia ?

Answer 12

• hydration
• analgesic
  -aggressive antibiotic therapy if infection is present
• intermittent transfusion
• hydroxyurea ( hydroxycarbamide ) an antitumor drug , is therapeutically useful because it inc circulating level of (Hb F )

Question 13

Hb C formed by replacement of…….. at the position ……. also in the ……..by ……

Answer 13

glutamate
6
β chain
lysine

Question 14

the cell don’t accept ……. shape in HbC but HbC ………with short life span resulting in ………

Answer 14

sickle shape
crystals
mild anemia

Question 15

during electrophoresis the C migrate …………….

Answer 15

more slowly toward anode than normal RBCs or Hb S

Question 16

do they suffer from infarctive crises , need therapy in HbC ?

Answer 16

no

Question 17

illustrate the cause of Hb SC

Answer 17

some β globin chains have the sickle cell mutation , other β globin chains have HbC

Question 18

…….. of the heme iron in Hb from Fe+2 to Fe3+ produce ………which ………bind O2

Answer 18

oxidation
met Hb
can’t

Question 19

what’s the reason for met Hb ?

Answer 19

genetic defect ( single base missense mutation ) in the alpha or beta globin chains in which ( tyrosine replaces proximal histadine )

Question 20

the met Hb chc by ………

Answer 20

chocolate cyanosis

Question 21

ttt of met Hb ……….

Answer 21

methylene blue

Question 22

def of quantitative hemoglobinopathy
and its type

Answer 22

• def: decrease rate of synthesis of globin
• type : β thalassemia
  α thalassemia

Question 23

illustrate the nature of lesions :
α thalassemia
β thalassemia

Answer 23

α thalassemia :
-defect of one or more of the 4 copies of α globin gene ( 2 on each chromosome 16 )
- result from deletional mutation
β thalassemia :
-defect of one or more of the 2 copies of β globin gene ( 1 on each chromosome 11 )
- there’s deficiency or a dec in synthesis of β globin chain

Question 24

which type of thalassemia appear only several months after birth?

Answer 24

β thalassemia ( compensation : inc HbA 2 , HbF )

Question 25

what is the same thing in both types of thalassemia ?

Answer 25

heterozygote advantage against malaria is seen in both of them (α , β thalassemia)

Question 26

list types of α thalassemia

Answer 26

1. α thalassemia carrier ( silent ) :
   - mutation only in one gene
   - patient normal but carrier
2. α thalassemia trait :
   - mutation in 2 genes
   - patient with mild anemia
   3.α thalassemia major ( Hb H ) :
   -mutation in 3 genes
   - patient with more severe anemia
3. Hb Bart ( hydrops fetalis ) :
   - mutation in 4 genes
   - embryo die in the uterus or soon after birth
   - there’s no α globin chains

Question 27

list types of β thalassemia

Answer 27

1. β thalassemia minor “ trait “ :
   -mutation occurs in one gene
   - mild anemia , normal life
2. β thalassemia major ( cooly anemia )
   - mutation in the 2 genes
   * as a compensatory mechanism gamma chain will be over produced skeletal changes as a result of extramedullary hematopoiesis

Question 28

ttt of cooly anemia

Answer 28

• repeated blood transfusion
• lead to iron overload “need iron chelator”