L5-types Of Normal And Abnormal Hb

Question 1

What are the other types of hemoglobin

Answer 1

HbA a2 B2
HbA2 a2 delta 2
HbF a2 y2
HbA1c a2 b2-glucose

Question 2

What is HbF

Answer 2

It’s a tetramer consisting of two alpha chains identical to those found in HbA plus two gamma chains

Question 3

What happens in the fifth week of gestation

Answer 3

Site of globin synthesis shifts first to the liver and then to the marrow and the primary product is HbF

Question 4

When does HBA synthesis occur

Answer 4

At about the eighth month of pregnancy and gradually replaces HbF

Question 5

Why does HBF have a higher oxygen infinity than HBA

Answer 5

Because HBF only has weak binding of 2,3BPG
2,3 BPG serves to reduce the oxygen affinity of hemoglobin
the weaker interaction between 2,3 BPG and HBF results in a higher oxygen affinity for HBF relative to HBA

Question 6

How is HBA slowly glycated
What does it depend on
Most abundant form

Answer 6

Nonenzymically condensed with hexose
Depends on plasma conc of hexose
Most abundant form is hbA1c(has glucose residues attached predominately to amino group of n terminal valines of b globin chains)

Question 7

What is the clinical importance of glycosylated HB A1c

Answer 7

It can be used as a marker to monitor the long-term glucose control along the previous 120 days
diabetic person with controlled fasting blood sugar level but with high HbA1c indicates that the patient has not been following the correct treatment instructions

Question 8

What is hemaglobinopathies

Answer 8

Defined as a group of genetic disorders caused by production of a structurally abnormal hemoglobin molecule, synthesis of insufficient quantities of normal Hb or rarely both

Question 9

What are the hemoglobinopathies

Answer 9

Sickle cell anemia
Methemoglobinemia
thalassemia

Question 10

Describe sickle cell anemia

Answer 10

Autosomal recessive disorder
Occurs in individuals who have inherited two mutant genes that code for synthesis of the beta chains of the globin molecules

Question 11

When does an infant show symptoms of sickle cell anemia

Answer 11

When sufficient HbF has been replaced by HbS

Question 12

What is the bio chemical and molecular defect in HBS

Answer 12

▪️Glutamate at position six has been replaced with Valine
▪️Forms a protrusion on the beta chain that fits into a complementary site on the beta chain of another hemoglobin molecule in the cell
▪️At low oxygen tension deoxyhemoglobin S polymerizes inside the RBC forming a network of insoluble fibers polymers that stiffen understood the cell producing Rigid misshapen RBC
▪️They block the flow of blood in the narrow capillaries and the interruption of the supply of O2 leads to anoxia in the tissue causing pain and eventually ischemic death of cells in the vicinity of the blockage
▪️ decreased ability to deform and an increased tendency to adhere to vessel walls, this makes moving through small vessels difficult thereby causing microvascular occlusion

Question 13

What is the clinical picture of sickle cell anemia

Answer 13

▪️Characterized by lifelong episodes of pain chronic hemolytic anemia with associated hyperbilirubinemia and increases susceptibility to infections usually beginning in infancy
▪️ Acute chest syndrome, stroke ,splenic and renal dysfunction and bone changes due to Marrow hyperplasia
▪️ heterozygotes do not show symptoms

Question 14

What are variables that increase sickling

Answer 14

Enhanced by any variable that increases the proportion of HBS in the deoxy state these variables include:
decreased PO2
increase PCO2
decreased pH
dehydration
an increased concentration of 2,3 BPG in RBCs

Question 15

How is sickle cell anemia diagnosed

Answer 15

Besides the clinical picture electrophoresis of hemoglobin obtained from the lysed RBC is routinely used in the diagnosis of sickle cell anemia
DNA analysis also is used
during electrophoresis at alkaline pH HBS migrates more slowly towards the anode than does HbA this altered majority of HBS is a result of the absence of the negatively charged glutamate residues in the two beta chains thereby rendering HBS less negative than HBA

Question 16

What is the treatment for sickle cell anemia

Answer 16

▪️Adequate hydration
▪️analgesics aggressive antibiotic therapy if infection is present
▪️and transfusion in patients at a higher risk for fatal occlusion of blood vessels
▪️Intermittent transfusions with packed RBCs reduce the risk of stroke with the benefits must be weighed against the complications of transfusion
▪️Hydroxyurea an antitumor drug is therapeutically you should because it increases the circulating levels of HbF which dec rbc sickling this leads to decrease frequency of painful crisis and reduces mortality
▪️Stem cell transplantation is possible

Question 17

What are the selective advantages of the heterozygous state

Answer 17

Less susceptible to the severe malaria caused by the parasite plasmodium falciparum this organism spends an obligatory part of its life cycle in the RBC

Question 18

What is the biochemical defect in Methemoglobinemia

Answer 18

Oxidation of the heme iron in hemoglobin from Fe2+ to Fe3+ Produces methemoglobin which cant bind to O2
Can be congenital or acquired

Question 19

What happens in the acquired cases of Methemoglobinemia

Answer 19

Oxidation by the action of certain drugs such as nitrates sulfanilamide drugs acetaminophen benzocaine and sodium nitroprusside or endogenous products such as reactive oxygen species

Question 20

What are the congenital causes of Methemoglobinemia

Answer 20

Substitution of histidine amino acid which links Oxygen by tryosine the thing that results in permanent oxidation of iron
Deficiency of NADH cytochrome b5 reductase the enzyme responsible for the conversion of methemoglobin to hemoglobin

Question 21

What is the clinical picture of Methemoglobinemia 

Answer 21

Characterized by chocolate cyanosis (a blue coloration of the skin and mucous membranes and brown colored blood) as a result of the dark colored methaemoglobin
symptoms are related to the degree of tissue hypoxia and include anxiety headache and Dyspnea
In rare cases coma and death can occur

Question 22

What is the treatment for Methemoglobinemia

Answer 22

Methylene blue and vit c which is a reducing agent causing reduction of iron and
repeat blood transfusion is required in case of HbM

Question 23

What is the biochemical defect in thalassemia

Answer 23

▪️Hereditary hemolytic diseases in which an imbalance occurs in the synthesis of Globin chains
▪️Most common single gene disorders in humans
▪️Synthesis of either alpha or the beta globin chain is defective and the hemoglobin concentration is reduced
▪️Can be caused by a variety of mutations including entire Gene deletions or substitutions or deletions of one of many nucleotides in the DNA

Question 24

What are the types of thalassemia

Answer 24

Beta thalassemias and alpha thalassemias 

Question 25

Describe beta thalassemias

Answer 25

Synthesis of Beta globin chain is decreased or absent as a result of point mutations
Increase HbA2 and HBf occurs
Only two copies of the beta globin gene in each cell

Question 26

What are the forms of beta thalassemia

Answer 26

Beta thalassemia trait (minor):if they have only one defective beta globin gene
Thalassemia (cooley anemia)major:if both genes are defective

Question 27

What is the clinical picture of beta thalassemia

Answer 27

Physical manifestation only occurs several months after birth
Those with thalassemia minor make some beta chains and do not require specific treatment
however those with thalassemia major are seemingly healthy at birth become severely anemic usually doing the first or second year of life due to ineffective erythropoiesis
skeletal changes as a result of extramedullary hematopoiesis are also seen
these patients require regular transfusions of blood
the only curative option available is hematopoietic stem cell transplantation

Question 28

Describe alpha thalassemia

Answer 28

Synthesis of alpha globin chain is decreased or absent

and typically as a result of deletion mutation

Question 29

Forms of alpha thalassemia

Answer 29

Silent carrier: if one of the four genes is defective no physical manifestations of the disease occur
Alpha thalassemia trait: If two alpha globe in genes are defective
Hemoglobin H beta 4 disease: If three alpha globe in genes are defective results in hemolytic anemia of variable severity
Hemoglobin bart y4: if all four alpha globin genes are defective disease with a Hydrops fetalis and fetal death results because alpha globin in chains are required for the synthesis of HbF

Question 30

Where is the advantage against malaria also seen

Answer 30

In alpha and beta thalassemias