Hemoglobin INDEX

See color plate.) Absorption coefficient of oxyhemoglobin and de-oxyhemoglobin as a function of wavelength. Source Based on data consolidated by Scott Prahl (Oregon Medical Laser Center) from various sources that are available at http //omlc.ogi.edu/spectra/ hemoglobin/index.html. 

Fig. 60. Representation of the 10 ligation states of hemoglobin X denotes ligation of a given chain or a metal substitution for Fe in a metal hybrid hemoglobin. Index numbers provide species designation. Subunit positions are shown in species 01. [Adapted from Ackers and Smith (1987)].

Recently, this problem has been approached by reverting to reading the color of the bilirubin directly. This used to be called an "Icterus Index", in which the color of the serum was compared to a dilute dichromate solution (39). However, the new approach has been to use two wavelengths. This can be used in either of two different procedures. In one procedure the reading is made at the peak for bilirubin which is at 453 nm and at an isosbestic point for hemoglobin (40). The effect on the reading due to hemoglobin is subtracted from the bilirubin value. Commercial instruments based on this principle have not been successful. 

A newer prognostic index uses similar risk factors except that poor performance status is replaced with low hemoglobin (less than 12 g/dL). Current research is focused on the prognostic importance of phenotypic and molecular characteristics of NHL. 

Fig. 2. Hill plot for oxygenation of human hemoglobin A as a function of the partial pressure (PO2) of molecular oxygen. The diagram at the right shows that the Hill coefficient will reach a limiting value of one at both extremes of ligand concentration. For this reason this cooperativity index is best measured at ligand concentrations near half-maximal saturation.

However, the mathematics describes an idealized situation, and the real situation in vivo may not be so straightforward. For example, with carbon monoxide, as already indicated, the toxicity involves a reversible interaction with a receptor, the protein molecule hemoglobin (see chap. 7 for further details of this example). This interaction will certainly be proportional to the concentration of carbon monoxide in the red blood cell. However, in vivo about 50% occupancy or 50% carboxyhemoglobin may be sufficient for the final toxic effect, which is cellular hypoxia and lethality. Duration of exposure is also a factor here because hypoxic cell death is not an instantaneous response. This time-exposure index is also very important in considerations of chemical carcinogenesis. 

Figure 14.3 Absorption spectra of water, skin melanin, hemoglobin, and fat. Also shown is the scattering spectrum of 10% intralipid, a lipid emulsion often used to simulate tissue scattering. Data are obtained from http //omlc.ogi.edu/spectra/index.html.

Bechtold WE, Sun JD, Bimbaum LS, et al. 1992a. S-phenylcysteine formation in hemoglobin as a biological exposure index to benzene. Arch Toxicol 66(5) 303-309. 

The error could as well be in the other sense we can have effects without dose. Toxicity of lead for example, is one of the present hot spots in environmental toxicology. One of the most sensitive biochemical indexes of this toxicity relates to the 7 step biosynthesis of hemoglobin, of which two steps are clearly inhibited b very low concentrations of lead in the human body (as reflected by the blood lead concentration). They result in a rapid increase of the delta-aminolevulinic acid concentrations in urine, of free erythroporphyrin in the circulating red blood cells and, in the worst cases, in a slight anemia. It... 

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