L5-types Of Normal And Abnormal Hb Flashcards
What are the other types of hemoglobin
HbA a2 B2
HbA2 a2 delta 2
HbF a2 y2
HbA1c a2 b2-glucose
What is HbF
It’s a tetramer consisting of two alpha chains identical to those found in HbA plus two gamma chains
What happens in the fifth week of gestation
Site of globin synthesis shifts first to the liver and then to the marrow and the primary product is HbF
When does HBA synthesis occur
At about the eighth month of pregnancy and gradually replaces HbF
Why does HBF have a higher oxygen infinity than HBA
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
How is HBA slowly glycated
What does it depend on
Most abundant form
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)
What is the clinical importance of glycosylated HB A1c
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
What is hemaglobinopathies
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
What are the hemoglobinopathies
Sickle cell anemia
Methemoglobinemia
thalassemia
Describe sickle cell anemia
Autosomal recessive disorder
Occurs in individuals who have inherited two mutant genes that code for synthesis of the beta chains of the globin molecules
When does an infant show symptoms of sickle cell anemia
When sufficient HbF has been replaced by HbS
What is the bio chemical and molecular defect in HBS
▪️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
What is the clinical picture of sickle cell anemia
▪️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
What are variables that increase sickling
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
How is sickle cell anemia diagnosed
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
What is the treatment for sickle cell anemia
▪️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
What are the selective advantages of the heterozygous state
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
What is the biochemical defect in Methemoglobinemia
Oxidation of the heme iron in hemoglobin from Fe2+ to Fe3+ Produces methemoglobin which cant bind to O2
Can be congenital or acquired
What happens in the acquired cases of Methemoglobinemia
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
What are the congenital causes of Methemoglobinemia
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
What is the clinical picture of Methemoglobinemia 
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
What is the treatment for Methemoglobinemia
Methylene blue and vit c which is a reducing agent causing reduction of iron and
repeat blood transfusion is required in case of HbM
What is the biochemical defect in thalassemia
▪️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
What are the types of thalassemia
Beta thalassemias and alpha thalassemias 
Describe beta thalassemias
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
What are the forms of beta thalassemia
Beta thalassemia trait (minor):if they have only one defective beta globin gene
Thalassemia (cooley anemia)major:if both genes are defective
What is the clinical picture of beta thalassemia
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
Describe alpha thalassemia
Synthesis of alpha globin chain is decreased or absent
and typically as a result of deletion mutation
Forms of alpha thalassemia
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
Where is the advantage against malaria also seen
In alpha and beta thalassemias
