What form of iron is required for hemoglobin, and what enzyme helps produce it?
Ferrous iron (Fe2+) is required for the binding of oxygen. Cytochrome b5 reductase reduces ferric (Fe3+) iron to the ferrous state. Ferric iron in the hemoglobin results in meth-hemoglobin.
What are the possible conformations of the hemoglobin tetramer, their names, and what causes each?
Hemoglobin may be in the Taut (T) or Relaxed (R) state. T conformation is due to salt bonds, hydrogen bonding, and hydrophobic interactions. R state occurs when bound to oxygen.
What are allostery and positive cooperatively?
Allostery occurs when the binding of a substrate at one location alters the protein conformation at other binding site. If allosteric changes lead to increased binding affinity at other sites, as in O2 and hemoglobin, it is termed positive cooperatively.
How is the oxygen dissociation curve arranged?
The oxygen dissociation curve shows the oxygen saturation of hemoglobin vs different partial pressures of oxygen. pO2 of room air is 130-160 (dep on elevation), thus the O2 sat is near 100%. In the tissues, the pO2 drops significantly, and the O2 sat drops as O2 is delivered to cells.
What causes the sigmoidal shape of the oxygen dissociation curve?
Positive cooperativity (PC) causes the sigmoidal shape of the curve. increased O2 binding (or dissociation) leads to more rapid binding (or dissociation) until all sites are bound (or unbound). This is shown in the difference between hemoglobin, a tetramer with PC, and myoglobin, a monomer whch cannot have PC.
What is the p50?
p50 is the partial pressure of oxygen at which 50% of hemoglobin is saturated. p50 of Hb A at standard conditions (37c, pH 7.4) is 27 mmHG)
What is the effect of lower pH on O2 dissociation?
Bohr effect. Lower pH shifts the curve to the right, resulting in less O2 bound at any pO2. That is, the lower the pH, the easier the dissociation. If you are exercising, extra lactic acid lowers pH, leading to more rapid O2 release in the tissues.
What efect does CO2 concentration have on O2 dissociation?
Inc CO2 concentration leads to decreased pH, and the Bohr Effect right shift of the curve.
What effect does temperature have on O2 dissociation?
Increased temp shifts curve to the right, decreasing O2 affinity. If you have a fever, you likley need more O2 to fight it, and this mechanism supplies that.
What is 2,3-BPG (2,3-DPG) and what effect does it have on O2 dissociation?
2,3-BPG is a by product of glycolysis and binds to the hemoglobin in a manner that stabilizes Hb in the T conformation. This shifts the dissociation curve to the right, releasing more O2. If glycolysis is increased, more O2 is needed in the cell, and more 2,3-BPG is prduced to get it there.
What are fetal and adult hemoglobins constructed of?
Fetal Hb is two alpha and two gamma chains. Adult Hb is two alpha and two beta chains or two alphas and two deltas.
What hemoglobins are made very early in embryonic development?
Hb Gower I, Hb Gower II, and Hb Portland. They are higher affinity Hbs that allow O2 uptake from maternel Hb.
What is fetal hemoglobin and what are its features?
Two alpha and two gamma chains. It dominates after 8 weeks of development. It has a higher affinity for O2 (left shifted curve) than regular Hb, which allows it to absorb O2 from maternal Hb. It does not bind well with 2,3-BPG, and has a more pronounced Bohr effect.
What are Heinz bodies and what are they associated with?
Heinz bodies are dark stains in RBS. They are the products of unstable hemoglobins.
What are general effects of high affinity hemoglobins?
P50 is left-shifted. Leads to relative tissue hypoxia, which stimulates the kidneys to release EPO. Increased EPO leads to increased RBC production. Affected individuals are typically well and don't need treatment (first ID'd in an 81 yo, so little impact on life).
What are general effects of low affinity hemoglobin?
P50 is right shifted. O2 is more easily released in the tissues. Often occurs with mild anemias because easier O2 release (opposite of hypoxia) leads to decreased EPO production, and thus decreased RBC production. Patients may have cyanotic appearance.
What is methemoglobin and what impact does it have on O2 affinity?
Methemoglobin is hemoglobin bound to Ferric iron (Fe3+) which cannot bind O2. This shifts the O2 dissociation curve to the left, decreasing P50 because of decreased positive cooperation. Normal level is only 1%. Appears brown when oxidized.
What causes congenitive methemoglobin?
Cytochrome b5 reductase deficiency. Causes up to 40% blood methemoglobin and blue appearance.
What causes acquired methemoglobinemia?
Exposure to certain drugs - phenacetin, benzocaine, dapsone, sulfa, etc. Well water contaminated with nitrates. Results in levels >40% and symptoms. Treated with methylene blue.
Why does methemoglobin appear easily in newborns?
Hemoglobin F oxidizes more readily to Ferric state and there is less cytochrome b5 reductase in the first few months of life. May result from exposure to well water, raw spinach, disinfectants, or benzocaine.
How does CO binding impact hemoglobin?
CO binds with 240x the affinity of O2. This decreases positive cooperation and shifts the dissociation curve to the left, futher than methemoglobin. Normal level 3%/ smokers 15%.
What are the signs, symptoms, and treatment of CO poisoning?
Headache, malaise, nausea, seizures, coma, MI. NOT cyanotic, but "cherry red". 40% present with late neurological effects - personality, movement, cognition. Treatment is 100% O2 or hyperbaric chamber (best).
How does a pulse oximeter work?
It compares the relative absorbance of red (660nm, peak deoxyhemoglin abs) and infrared (940nm, peak oxyhemoglobin abs) light to determine the percentage of oxygenated hemoglobin.
What are some flaws of pulse oximetry?
Shock and severe anemia give false readings; doesn't measure CO2, O2 carrying capacity, or abnormal Hbs with CO poisoning or methemoglobin. Also is affected by probe placement, mechanical malfunction, movement (shivering, seizures), nail polish, and deeply pigmented skin.