A 26-week-old baby was brought to the pediatric clinic because of increasing lethargy and cyanosis. The infant has been in good health at birth, and the mother had attempted breast-feeding. A blood sample was collected and a positive test for methemoglobinemia was obtained. The baby then was treated with intravenous ascorbate and methylene blue. Within 2 days the child was alert, and the cyanosis had disappeared. It is known that methemoglobin has absorption spectra maxima at 500 nm and 631 nm. Answer the following questions:

a. What is the chemical difference between hemoglobin and methemoglobin, and how do their oxygen capacities compare?
b. How do you analyze the sample blood to detect methemoglobin?
c. What is the cause of the cyanosis associated with toxic methemoglobinemia?
d. What is the biochemical basis for treatment of toxic methemoglobinemia with ascorbate and methylene blue?

a,

This is due to differences in the oxidation states of  Fe. atoms present in the two protein pigments.

Generally,the Fe2+ atom in the heme groups is responsible for the  oxygen carrying capacities of haemoglobin in RBC.However,in +2 state that Fe carry oxygen through cooperative binding in the blood.When methemoglobin is formed the Fe exits in +3,and therefore can not bind oxygen. Methemoglobin is a mettaloprotein of Fe3+ states. It results from the oxidation of  Fe atoms in Hb from Fe2+ to Fe3+ states,during exposure to certain medications,and some nitrate,certain  dyes and some compounds.

This can be conducted with CO-oximeter.This is a device used to measure the blood  percentage oxygen saturation levels.It conduct this by measuring the oxygen carrying capacity of haemoglobin in a blood sample. Since oxygen saturation levels of a blood sample depends on the amount of Hb,therefore by passing some wavelengths of light across the blood samples,The more the wavelength of lights absorbed by the blood samples, the more the percentage saturation of the blood sample with oxygen,and therefore the oxygen carrying capacity of the blood,thus more Hb.

Hence, if the blood sample absorbs  wavelength of light in the range of (500 nm and 631 nm.) it shows that little Hb is present in the blood samples,and the blood should contain Methemoglobin of Fe3+ and not Hb.

Methemoglobinemia is  a condition in which methmoglobin concentration of the blood rises,due to the higher percentage of Hb,with F3+( of poor oxygen carrying capacity or uncoupling ) compare to normal F2+ for carrying oxygen. Since these can not transport oxygen,Cyanosis results as the baby turns blue,with lack of oxygen.

Since the rise in the concentration of methmoglobin is the major cause of this condition,reduction of it concentration is the primary step.Therefore, the Methylene blue role is to reduce the amount  of  methmoglobin by enzyme NADPH-methemoglobin reductase.This occurs with 10-60mints after administration.Thus the concentration of these pigment is reduced,likewise its toxic levels.

Ascorbate can also be used,however a lot of doses is required for this to have a significant effects,and compare to Methylene blue it is less effective.,

Explanation