Clinical cases and Situational tasks

83. HbA consists of 2 α - and 2 β- polypeptide chains; HbF – of 2 α - and 2 γ - polypeptide chains. That makes HbF much more related to oxygen than HbA. Explain biological significance of this condition?

Answer: HbF binds 2,3 - diphosphoglyciric acid weaker than that of HbA, because of its higher affinity to O₂. This helps fetus to obtain oxygen from maternal blood.

84. Explain how to differentiate kidney retention and productive azotemia by the content of rest nitrogen in blood serum and total nitrogen in urine?

Answer: Increased concentration of rest nitrogen accompanied by elevated nitrogen content in urine leads to productional azotemia. Low concentration of urine nitrogen explains kidney disease.

85. Specify the direction of movement of hemoglobin molecules under the conditions of electrophoresis at pH 4.8.

Answer: In acidic medium (pH 4.8) hemoglobin exists in the form of the cation, because the excess of protons in the environment slows dissociation of carboxyl groups of amino acids of globin. During electrophoresis hemoglobin moves from the starting line to cathode, a negatively charged electrode.

86. Examination of the blood of cancer patient revealed that concentration of the rest nitrogen was about 60 mmol/l, renal function was not impaired. What causes this condition? What kind of azotemia is observed?

Answer: These indexes indicate increased breakdown of tissue proteins with increasing of toxic processes. Such state is typical for productive azotemia.

87. A 25-year-old Mediterranean pregnant female has a history of asymptomatic mild hypochromic, microcytic anemia, elevated hemoglobin A2 and F on electrophoresis. Her brother had severe hemolytic disease that required transfusions and ultimately caused his premature death at age 10. She is diagnosed with β-thalassemia minor. What is the molecular genetics behind this disorder? What was the likely test and what is the biochemical basis?

Answer: Molecular genetics: Impaired production of β-globin peptide chain. Numerous mutations have been identified in the production of ribonucleic acid (RNA) including in the promoter region and splice junctions. Likely test: Oligonucleotide probe. After chorionic villus sampling is performed, a radioactive probe can be used and hybridized with specific genetic mutations in the fetus’ deoxyribonucleic acid (DNA), allowing for prompt detection and prenatal diagnosis.

88. An electrophoretic analysis of patient’s hemoglobin indicates that there is a decrease in the relative amount of the β-chain with respect to the α-chain, both the β- and the α-chains migrate at the same position as normal chains. Most likely his anemia is caused by the following condition?

Answer: Since the β-chain is decreased with respect to the α-chain, it is most likely that there is a mutation that decreases the expression of the β-chain gene, in which a mutation in the promoter region could result. A point mutation in the β-chain leading to an amino acid substitution could lead to changes in electrophoretic mobility but would not alter the levels of expression. A frameshift mutation in the β-chain would result in decreased β-chain on the electrophoregram.