Normal adult hemoglobin is called Hemoglobin A (Hb A). Ninety-eight percent of a
ID: 90971 • Letter: N
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Normal adult hemoglobin is called Hemoglobin A (Hb A). Ninety-eight percent of adult hemoglobin Hb A and 2% is Hb A2. There are other forms of hemoglobin. For example, the developing fetus has a different kind of hemoglobin than most normal adults. Fetal hemoglobin (or Hemoglobin F) consists of two a chains and two Y chains, whereas adult hemoglobin (Hemoglobin A) consists of two a chains and two B chains. Fetal hemoglobin is synthesized beginning at the third month of gestation and continues up through birth. After the neonate is born, hemoglobin F synthesis declines (because synthesis of the y chain declines) and hemoglobin A is synthesized (because synthesis of Bchains begins). By the time the baby is six months old 98% of its hemoglobin is Hemoglobin A. There is also a mutant form of hemoglobin called Hemoglobin S which is found in persons with the disease sickle cell anemia. The disease sickle cell anemia is one of the major health problems facing the African-American community. The World Health Organization estimates that 250,000 babies world- wide are born with sickle cell anemia. Currently there is no cure. A person afflicted with sickle cell anemia has inherited a defective gene from each parent. (Parents who are carriers of the sickle cell gene are heterozygous AS, whereas the person afflicted with sickle cell anemia is SS, non-carriers are designated AA.) The defective gene is the one coding for the B-chain. The amino acid at position 6 on each B chain has been mutated from a glutamate to a valine. Normal a chains have a decreased affinity for the mutated Bchains; thus assembly of the HbS tetramer is more difficult. Red blood cells containing HbS form a sickle shape because the Hb S molecules polymerize. Hb S molecules are more likely to polymerize when in the deoxygenated T form than in the oxygenated R form. The polymerized Hb deforms the normal discoid shape of the red blood cells, producing a sickle-shaped cell. The sickle shaped red blood cells become trapped in capillaries and organs, depriving the victim of adequate oxygen supply and causing chronic pain and organ damage In this case we will consider our patient, a 10-year-old black male child named Michael B., who was admitted to the hospital because he was experiencing severe chest pain. He had been hospitalized on several previous occasions for vaso-occlusive episodes that caused him to experience severe pain that could not be managed with non-prescription drugs such as ibuprofen. He was slightly jaundiced, short of breath and easily tired, and feverish. A chest x-ray was taken and was abnormal. An arterial blood sample showed a po2 value of 6 kPa (normal is 10-13 kPa)Explanation / Answer
This question has multiple sub questions. As per Chegg’s policy, I am answering the first question. However, I am answering all the questions except the first question. This is because the first question is incomplete. The first part of it cropped from the image.
Q2.
Hb S carries a mutation which encoded valine in place of Aspartic acid. The said amino acid is on the surface of the haemoglobin chain when it folded in to its proper confirmation. Usually, surface of the folded proteins contain hydrophilic amino acids which can interact with surrounding water. But, Valine is hydrophobic amino acid which means it will not interact with water. In such case, haemoglobin molecules prefer to interact with each other than interacting with water. This results in formation of clumps.
This will not occur if there is no Asp to Val mutation. So, Hb A will not form clumps.
Q3.
Clumping occurs at increased rate when there is less oxygen. If haemoglobin is in de-oxy state (T-state), a different hydrophobic region in the haemoglobin protein will be automatically exposed. Mutated region of one HbS molecule will interact with this newly exposed hydrophobic region to form the fibres. Each fibre contains seven haemoglobin tetramers. Such fibres, then associate with other fibres forming a large fibre. We call this clumping.
Providing excess oxygen keeps the haemoglobin in oxygenated state (R-state). This will reduce the chance of fibre formation.
Q4.
a.
Foetal haemoglobin contains alpha and gamma chains. Adult haemoglobin has alpha and beta chains. Sickle cell mutation is in beta chain. Therefore adult haemoglobin is affected but foetal haemoglobin is not affected. Fetal haemoglobin will not form clumps.
So, inducing the expression of foetal haemoglobin will help in relieving sickle cell anaemia symptoms.
b.
Nitrosyl -haemoglobin prefers R state over T state. R state is less prone to clumping. So, keeping the haemoglobin in R state helps in preventing lumping and this relieves symptoms.
c.
Clumping of Hb S permanently distort RBCs into a sickle shape and reduces their elasticity. These rigid and sickle cell shaped RBCs will not be able to pass freely through the capillaries in the tissues. This often results in vessel occlusion and ischemia.
NO induces vasodilation. Sickle cell RBCs can move relatively easily through the dilated capillaries. This will help in restoring normal blood flow to the tissues and relieves symptoms.
Q5.
Sickle cell anaemia is a genetic disease. It shows autosomal recessive inheritance. RBC production takes place in bone marrow. If we can transplant bone marrow containing normal genotype for beta chain, those cells will produce normal haemoglobin and RBCs.
Q6.
Assuming that both parents do not have sickle cell anaemia, we can believe that both of them are carriers.
Therefore, one of the four children will be having disease and two out of four will be carriers and one out of four will be phenotypically as well as genotypically normal. If they have four children, one will be the disease. This is by random chance. It is also possible that two consecutive pregnancies may produce children with disease. Therefore, we cannot be sure that they will get normal child next time.
I advise them to go for genetic testing when the mother conceives second time. Through amniocentesis, foetal cells can be collected and mutations can be screened. If the foetus is homozygous for the sickle cell mutation, he/she would get the disease. The parents may be given a chance to terminate the pregnancy, if it is legally permitted in their country.
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