Transcript Document

PHYSIOLOGY OF THYROID GLAND
ENDO BLOCK 412
Dr. Shaikh Mujeeb Ahmed
Assistant Professor
AlMaarefa College
Objectives
• The student should be able to:
• Describe the distribution of iodine in the body, dietary
requirements for iodine and thyroid uptake of iodine.
• Identify the structure and formula for thyroxine (T4) and
triiodothyronine (T3).
• Know the basic steps involved in the biosynthesis of T3 and T4.
• Identify the bound forms and quantities of T3 and T4 in circulation.
• Relate the plasma half-life of thyroid hormones to their biological
effects.
• Describe the effects of TSH on thyroid activity.
• Describe the relationship of TSH, and TRH to T4 secretion.
• Know the physiological effects of thyroid hormone.
• Indicate the relative activities of T4 and T3.
• Describe the etiology, symptoms and treatment of thyrotoxicosis
and hypothyroidism.
Physiologic Anatomy of the Thyroid Gland
•located immediately
below the larynx on each
side of and anterior to
the trachea
•one of the largest of the
endocrine glands
•secretes two major
hormones, thyroxine and
triiodothyronine,
commonly called T4 and
T3, respectively
Anatomy of thyroid gland
• The gland is composed of
– large numbers of closed follicles (100 to 300
micrometers in diameter)
– filled with a secretory substance called colloid and
– lined with cuboidal epithelial cells that secrete
into the interior of the follicles.
– The major constituent of colloid is the large
glycoprotein thyroglobulin, which contains the
thyroid hormones within its molecule.
Fig. 19-1b, p. 692
• Interspersed in the interstitial spaces between
the follicles is another secretory cell type, the
C cells, which secrete the peptide hormone
calcitonin.
IMPORTANT
 Thyroid gland maintains the level of metabolism in the
tissues that is optimal for their normal functioning
 Thyroid hormone stimulate the O2 consumption of most of
the cells in the body
 Help to regulate the lipid & carbohydrate metabolism &
are necessary for normal growth & maturation
• Thyroid gland is not essential for life but its absence
causes
– Mental & Physical slowing
– Poor resistance to cold
– In children mental retardation & dwarfism
Unique features of thyroid hormone
synthesis
• Thyroid hormone contain large amount of
iodine
• Synthesis of thyroid hormone is partly
intracellular & partly extra cellular & is stored
in follicular lumen.
• T4 is major secretary product of thyroid gland
but it is not the most active form.
Iodine requirement
• Iodine is essential for synthesis of thyroid
hormone
• About 1 mg/week iodine is required to prevent
• iodine deficiency
• Minimum daily iodine intake is 150 µg in adults
• Normal plasma iodine level is 0.3 µg/dl
Thyroid hormones
• two iodine-containing hormones derived from
the amino acid tyrosine:
• Tetraiodothyronine (T4, or thyroxine) and
• Tri-iodothyronine (T3).
• The prefixes tetra and tri and the subscripts 4
and 3 denote the number of iodine atoms
incorporated into each of these hormones.
Steps in the synthesis of thyroid
hormones
• Iodide Pump (Iodide Trapping)
• TSH stimulates and hypophysectomy greatly
diminishes the activity of the iodide pump in
thyroid cells.
• Oxidation of the Iodide Ion.
• This oxidation of iodine is promoted by the
enzyme thyroperoxidase (TPO).
Steps in the synthesis of thyroid
hormones
• Iodination of Tyrosine and Formation of the
Thyroid Hormones— “Organification” of
Thyroglobulin.
• Attachment of one iodine to tyrosine yields
monoiodotyrosine (MIT)
• Attachment of two iodines to tyrosine yields diiodotyrosine (DIT).
• Coupling of one MIT (with one iodide) and one
DIT (with two iodides) yields tri-iodothyronine,
or T3
Steps in the synthesis of thyroid
hormones
• Coupling of two DITs (each bearing two iodide
atoms) yields tetraiodothyronine (T4, or
thyroxine).
• Thyroid hormones remain stored in this form
in the colloid until they are split off and
secreted
• To secrete thyroid hormone, the follicular cells
phagocytize thyroglobulin-laden colloid.
Storage of Thyroglobulin
• The thyroid gland is unusual among the
endocrine glands in its ability to store large
amounts of hormone.
• Stimulation of thyroid cells by TSH
– Iodinated thyroglobulin is taken back into follicular
cells
– Lysosomal enzyme digest thyroglobulin
– Release T4 & T3 in circulation
– Leftover MIT & DIT are deiodinated.
• In circulation most of T3 & T4 is bound to
thyroxine binding globulin (TGB).
– In hepatic failure TGB level decreases – decrease
in total thyroid hormone level.
– In pregnancy TGB level increases – increase in
total thyroid hormone level.
• In peripheral tissues T4 is converted to T3 or to
rT3
– T3 is biologically more active than T4.
– rT3 is inactive.
Synthesis, storage, and secretion of
thyroid hormone
Chemical structure of thyroid hormone
Metabolism of Thyroxine by
Deiodination in Peripheral Tissues
I
HO
O
5’/3’-deiodinase
I
HO
I
H
H
C
C
H
NH2
H
H
C
C
H
NH2
COOH
I
T3
I
O
I
H
H
C
C
H
NH2
COOH
I
T4
I
5/3-deiodinase
HO
I
O
I
RT3
COOH
Thyroxin and its precursors: Structure
& Synthesis
Regulation of thyroid hormone
secretion
Actions of thyroid hormone
• Thyroid hormone is the main determinant of
the basal metabolic rate and exerts other
effects as well.
• Effect on metabolic rate and heat production
– increases the body’s overall basal metabolic rate
– Regulates the body’s rate of O2 consumption and
energy expenditure
– its calorigenic (“heat-producing”)
Basal metabolic rate (BMR)
•
•
•
•
 Na+ - K+ ATPase.
 O2 consumption
 heat production
 BMR
EFFECT ON INTERMEDIARY METABOLISM
• Overall metabolism is increased
• Glucose absorption from GIT is increased
•  Glycogenolysis, gluconeogenesis & glucose
oxidation
•  lipolysis
•  protein synthesis & catabolism (overall
catabolic effect)
Growth
• Attainment of adult stature
• Acts synergistically with growth hormone &
somatomedins to promote bone formation
• Stimulate bone maturation
Central nervous system
• Perinatal period
– Maturation of the CNS is absolutely dependent on
thyroid hormone
– Thyroid hormone deficiency causes irreversible
mental retardation
• Adulthood
– Hperthyroidism causes hyperexcitability and
irritability
– Hypothyroidism causes decrease mental capacity
& impaired memory
Autonomic nervous system
• Has same actions as sympathetic stimulation
• Up regulate β1 adrenergic receptors in the
heart.
Cardiovascular and Respiratory system
• Increase cardiac output
– Increase heart rate
– Increased stroke volume
• Increased ventilation
Effects of thyroid hormone summary
•
•
•
•
Effect on metabolic rate and heat production
Sympathomimetic effect
Effect on cardiovascular system
Effect on growth and nervous system
References
 Human physiology, Lauralee Sherwood, seventh
edition.
 Text book physiology by Guyton &Hall,11th
edition.
 Text book of physiology by Linda .S .Costanzo third
edition
32