Biomedical Engineering Reference
In-Depth Information
The iodine is then reused in the cell, repeating the enzyme reactions to form the thyroid
hormones.
Once in the plasma, the thyroid hormones reversibly combine with proteins. The binding
to proteins protects T4 and T3 from immediate metabolism and excretion as they are inac-
tive in this mode. T4 binds primarily with thyroid binding globulin (TBG) and, to a lesser
extent, to thyroxine-binding prealbumin (TBPA) and albumin. TBG in the plasma is present
in low concentrations and has a high affinity for T4; it usually binds about 70 percent of the
available T4. TBPA in the plasma is present in high concentrations but has a low affinity for
T4. Ten percent of the plasma-bound hormone T4 is used each day, giving it a 7-day half-
life. The 7-day half-life for T4 creates a stable pool of thyroid hormone in the plasma.
Approximately 0.04 percent of the T4 is not bound to proteins in the plasma during normal
conditions, and we call the unbound T4
T4.
T3 has a lower binding affinity for plasma proteins. Those T3 that are bound are primar-
ily with TBPA and albumin. T3 is rapidly cleared from the plasma with a half-life of 1 day.
Approximately 10 percent of T3 is not bound to proteins in the plasma during normal
conditions.
While a small amount of T3 is released by the thyroid into the plasma, almost all of the
T3 in the plasma is produced by deiodination enzymes in the liver and to a much lesser
extent in the kidneys, where an iodine atom is removed from T4 that converts it into T3.
T4 is also eliminated within the liver and to a lesser extent in the kidneys, by conjugation
of sulfate or glucuronic acid with the phenolic hydroxyl group of the outer phenolic ring,
turning T4 into T3. Also within the liver, T4 undergoes deamination and decarboxylase
reactions that convert it into T3.
Once in the plasma, free-T3 moves into the interstitial space and easily moves across the
cell membranes in the tissues. When transported into the cells, free-T3 moves into the cell
nucleus and binds with thyroid hormone receptors, which then synthesize new proteins
through gene transcription. These new proteins are connected to energy metabolism, body
temperature, body weight, and the control of growth, reproduction, and differentiation.
While T4 also moves into the cell and binds with thyroid hormone receptors, it takes about
10 times more T4 than T3 to equal the effect of T3 in gene transcription.
Example Problem 7.16 involves a three-compartment model describing the transport of
T4 throughout the body. To model the transport of T4 in the body, a bolus of radioactive
iodine-T4 is injected into the plasma. The use of radioactive iodine-T4 allows us to track
the transport of T4 in the body apart from the natural T4. The pathways of interest in the
following example, as described in Figure 7.25, involve the plasma, liver, and hepatic duct.
free-
f
1
(t)
K
12
q
1
q
2
q
3
K
23
K
21
FIGURE 7.25
Illustration for Example Problem 7.16. Compartment 1 is the plasma, compartment 2 is the liver,
and compartment 3 is the hepatic duct, simplified to a single compartment. The input
f
1
(
t
) is a bolus of radioactive
iodine-T4.
