Biomedical Engineering Reference
In-Depth Information
7.7.4 Sink Compartment
A sink compartment in a three-compartment model gives rise to a zero root and is
described as a compartment with only inputs and no output to other compartments except
to the environment. The solution for the sink compartment is found as usual using the
D-Operator approach from the resulting quantities in the other two compartments.
To illustrate a sink compartment, Example Problem 7.16 involves a three-compartment
model describing the transport of a thyroid hormone to the hepatic duct (sink compart-
ment).
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The thyroid system was first described in Example Problem 7.5 and is extended
to this example. We will then extend the model in Section 7.8.4. Before describing the cur-
rent model, more background material on the thyroid system is presented.
The thyroid hormones thyroxine (T4) and triiodothyronine (T3), which are produced by
the thyroid gland, maintain the body temperature, regulate energy metabolism, and are
important for growth and development. The thyroid hormones themselves do not exist
inside the thyroid cell but are part of a large thyroglobulin molecule that consists of approx-
imately 70 tyrosine amino acids. The metabolic rate falls to approximately 50 percent of nor-
mal without these hormones, and too much thyroid hormone can increase the metabolic
rate by 100 percent above the normal rate. The pituitary gland controls the discharge of
T4 and T3 through its release of the thyroid-stimulating hormone, TSH. As previously
described, the pituitary gland is under the control of the hypothalamus through its release
of the thyrotropin-releasing-hormone, TRH.
Ingested iodine, in the form of iodide, is an essential element in the formation of thyroid
hormones. Blood flow through the thyroid gland is among the highest of any organ in the
body, which allows the quick uptake of iodide. Typically after ingestion, 80 percent of the
iodide is rapidly excreted by the kidneys, and the other 20 percent is taken up by the thy-
roid gland.
Once iodide is taken up by the thyroid gland, it is used in a series of enzyme reactions to
create the thyroid hormones. Iodide is first transported across the membrane of the thyroid
cell by a pump mechanism called the sodium-iodide symporter. The pump allows iodide con-
centrations in the thyroid cell to be much greater than in the plasma. Once inside the cell,
iodide is oxidized by thyroidal peroxidase to iodine, which iodinates the tyrosine component
of the thyroglobulin molecule to first formmonoiodotyrosine (MIT) and then diiondotryosine
(DIT). Thyroperoixidase then catalyzes the joining of two molecules of DIT to form T4 (a two-
benzene ringed structure consisting of an inner tyrosyl ring and an outer phenolic ring, within
the thyroglobulin-iodine molecule) or to a lesser extent, the joining of one molecule of MIT to
DIT to form T3. Reverse T3 is also formed but is excluded from this discussion.
While the process of creating the thyroglobulin-iodine molecule is quick, the thyroid
gland keeps approximately a 60-day supply in reserve. Thyroglobulin itself is not released
into the plasma when the thyroid is stimulated by TSH, but T4 and T3 are released through
a lysosomal protease enzyme action on the thyroglobulin-iodine molecule. Almost all of the
output from the thyroid gland is T4 (greater than 90 percent). In addition, MIT and DIT are
released from the thyroglobulin-iodine molecule when T4 and T3 are released; however,
MIT and DIT do not leave the cell but are deiodinated, allowing the release of iodine.
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See Haddad et al., 2003, in references for original problem developement.
