The ability of acidosis to precipitate a crisis in sickle cell anemia can be explained as follows: Acidosis, which refers to a decrease in pH, reduces the solubility of HbS (sickle hemoglobin). This decreased solubility causes the oxygen-dissociation curve to shift to the right, indicating a decrease in oxygen affinity and an increase in oxygen delivery. This shift favors the formation of the deoxy (taut) form of hemoglobin and can potentially trigger a sickle cell crisis. Additionally, acidosis increases the binding of 2,3-bisphosphoglycerate to hemoglobin, as this molecule only binds to the deoxy form of hemoglobin.

Regarding the binding of oxygen by hemoglobin, the following statements are correct: When oxygen binds to one heme group, it increases the oxygen affinity of the remaining heme groups within the same hemoglobin molecule. An increase in pH leads to a rise in oxygen affinity, while carbon dioxide lowers oxygen affinity by decreasing pH. Carbon dioxide also binds to the N-termini, stabilizing the deoxy form of hemoglobin. Hemoglobin binds one molecule of 2,3-bisphosphoglycerate. Proton affinity is greater in deoxyhemoglobin compared to oxyhemoglobin.

The substitution of β-lysine 82 by methionine in HbA results in Hb Helsinki. In Hb Helsinki, the ability of 2,3-bisphosphoglycerate (2,3-BPG) to bind to the β subunits of hemoglobin is reduced due to the decreased interaction with negatively charged phosphate groups. As 2,3-BPG normally decreases the oxygen affinity of hemoglobin, a reduction in 2,3-BPG leads to increased oxygen affinity and decreased oxygen delivery to tissues. The taut form of hemoglobin is stabilized in Hb Helsinki. Consequently, there is a leftward shift in the oxygen-dissociation curve. It is important to note that this condition does not result in anemia, as increased red blood cell production compensates for the decreased oxygen delivery.

In the case of the 67-year-old man who presented with angina and shortness of breath, along with a blue discoloration of his face and extremities, the most likely diagnosis is carboxyhemoglobinemia. This condition is characterized by the presence of excessive carboxyhemoglobin, which gives blood a brown appearance.
.2. Which one of the following statements concerning the ability of acidosis to precipitate a crisis in sickle cell anemia is correct?
A. Acidosis decreases the solubility of HbS.
B. Acidosis increases the oxygen affinity of hemoglobin.
C. Acidosis favors the conversion of hemoglobin from the taut to the relaxed conformation.
D. Acidosis shifts the oxygen-dissociation curve to the left.
E. Acidosis decreases the ability of 2,3-bisphosphoglycerate to bind to hemoglobin.
Correct answer = A. HbS is significantly less soluble in the deoxygenated form, compared with oxyhemoglobin S. Decreased pH (acidosis) causes the oxygen-dissociation curve to shift to the right, indicating decreased oxygen affinity (increased delivery). This favors the formation of the deoxy, or taut, form of hemoglobin and can precipitate a sickle cell crisis. The binding of 2,3bisphosphoglycerate is increased, because it binds only to the deoxy form of hemoglobin.
.3. Which one of the following statements concerning the binding of oxygen by hemoglobin is correct?
A. The Bohr effect results in a lower oxygen affinity at higher pH values.
B. Carbon dioxide increases the oxygen affinity of hemoglobin by binding to the C-terminal groups of the polypeptide chains.
C. The oxygen affinity of hemoglobin increases as the percentage saturation increases.
D. The hemoglobin tetramer binds four molecules of 2,3bisphosphoglycerate.
E. Oxyhemoglobin and deoxyhemoglobin have the same affinity for protons.
Correct answer = C. The binding of oxygen at one heme group increases the oxygen affinity of the remaining heme groups in the same molecule. A rise in pH results in increased oxygen affinity. Carbon dioxide decreases oxygen affinity because it lowers the pH. Moreover, binding of carbon dioxide to the N-termini stabilizes the taut, deoxy form. Hemoglobin binds one molecule of 2,3-bisphosphoglycerate. Deoxyhemoglobin has a greater affinity for protons than does oxyhemoglobin.
.4. β-Lysine 82 in HbA is important for the binding of 2,3-bisphosphoglycerate. In Hb Helsinki, this amino acid has been replaced by methionine. Which of the following should be true concerning Hb Helsinki?
A. It should be stabilized in the taut, rather than the relaxed, form.
B. It should have increased oxygen affinity and, consequently, decreased oxygen delivery to tissues.
C. Its oxygen-dissociation curve should be shifted to the right relative to HbA.
D. It results in anemia.
Correct answer = B. Substitution of lysine by methionine decreases the ability of negatively charged phosphate groups in 2,3-bisphosphoglycerate (2,3-BPG) to bind the β subunits of hemoglobin. Because 2,3-BPG decreases the oxygen affinity of hemoglobin, a reduction in 2,3-BPG should result in increased oxygen affinity and decreased oxygen (O2) delivery to tissues. The relaxed form is the high-oxygen-affinity form of hemoglobin. Increased oxygen affinity (decreased delivery) results in a left shift in the oxygen-dissociation curve. Decreased delivery of O2 is compensated for by increased RBC production.
.5. A 67-year-old man presented to the emergency department with a 1-week history of angina and shortness of breath. He complained that his face and extremities had taken on a blue color. His medical history included chronic stable angina treated with isosorbide dinitrate and nitroglycerin. Blood obtained for analysis was brown. Which one of the following is the most likely diagnosis?
A. Carboxyhemoglobinemia