Thyroid gland structure (week 2) Flashcards
what are c cells also known as and what do they secrete
parafollicular cells and they secrete calcitonin, a peptide hormone which can cause medullary carcinomas
what is a medullary carcinoma
this can happen when c cells become cancerous and grow out of control
what are thyroid epithelial cells also known as and what are they organised into
thyrocytes they are organised into spherical follicles
what hormones are secreted by the thyroid
T3, T4 these are the thyroid hormones
what is colloid
it is a glycoprotein
what do follicular cells secrete
thyroid hormone
what is 3,5,3’,5’-tetraiodothyronine also known as
thyroxine (T4)
what is 3,5,3’-triodothyronine known as
triiodothyronine (T3)
which is secreted in a greater amount T3 OR T4
T4 however T3 is more potent
how is T4 converted into T3
by a deiodinase which is an enzyme found in many peripheral tissues
what does T3 bind to
to T3 receptors that bind with high affinity (TR alpha and TR beta)
what are the three deiodinases
type 1,2,3
explain type 1 deiodinase
(low affinity, Km of microM) occurs in tissue with high blood flow and rapid exchanges with plasma,
explain type 2 deiodinase
(high affinity, Km of nM) expressed by glial cells in CNS, provides T3 even when free T4 falls to low levels
explain type 3 deiodinase
is the physiologic inactivator of thyroid hormones, catalyzing the inner ring deiodination of thyroxine (T(4)) to reverse triiodothyronine (rT(3)) and (T(3)) to 3, 3’-diiodothyronine (T(2)), both of which are biologically inactive.
what is thyroglobulin and what is its function
a protein made by the thyroid and it stores iodide
Thyroid hormone synthesis in thyrocytes
-Thyroglobulin (TG/TRG) is synthesized by thyroid epithelial cells, secreted into lumen of follicle. One TG contains
- Iodide taken from blood to colloid through Sodium-iodide symporter
-Enzyme thyroid peroxidase synthesises thyroid hormones and catalyses
1) iodination
2) coupling sequential reactions
-
how many amino acids make up thyroglobulin
5500 amino 134 residues, makes up most of the follicular colloid
How much iodide is ingested and secreted daily
400 micrograms
What are some minimum daily requirements of iodide needed in humans
150 micrograms for adults
90 to 120 micrograms for children
200 micrograms for pregnant women
How much iodide is taken up daily by the thyroid and what is the thyroids overall iodide content
70-80 micrograms taken up daily
Total content is about 7500 micrograms
What is the ratio of iodide stored in the form of hormones
100:1
Physiological effects of thyroid hormone
Effects on cellular differentiation and development on the nervous system in particular
Effects on metabolic pathways and use of carbohydrates, lipids and proteins
Explain how T3 and T4 promote accelerated metabolism
Increase oxygen consumption and increase heat production
Help regulate basal metabolic rate and body temperature
Increase carbohydrate, fat and protein turnover, ensuring that adequate cellular energy is available to support metabolically demanding activities
Why are thyroid hormones important during development and growth
TH promote growth and stimulate maturation of central nervous system
Between week 11 and birth TH is essential
Cardiovascular and respiratory effects TH
Alters the expression of Ryanodine Ca2+ channels in the sarcoplasmic reticulum, promoting Ca2+ release
Enhances the sensitivity and expression of adrenoreceptors to stimulation by noradrenaline
Effects on basal membrane TH
Thyroid hormones increase the:
Basal rate of oxygen consumption
Heat production
Adjust heat loss through sweating and ventilation
Changes in body temperature parallel fluctuations in thyroid hormone availability
Effects on autonomic nervous system and catecholamine TH
Increasing the number of beta- adrenergic receptors in heart muscle
Increasing the generation of intracellular second messengers, such cAMP
TRH
TSH
meaning
Thyrotopic releasing hormone
Thyroid stimulating hormone
TSH stimulates synthesis of release of T3 and T4
Hyperthyroidism effects
Increase HR
Increased cardiac contractility
Increased cardiac output
Decreased peripheral vascular resistance
Increased renal flow
Hypothyroidism effects
Decreased HR
Decreased contractility
Decreased cardiac output
Increased peripheral vascular resistance
Decreased Renal blood flow
How is hyperthyroidism caused
Autoimmune disease (Graves’ disease) autoantibodies (immunoglobulins) that stimulate thyrotropin receptors on thyroid gland follicle cells leading to continual stimulation of thyroid hormone synthesis.
Benign tumour of thyroid cells causing enlargement of gland and increased hormone secretion
Excessive secretion of TSH from a TSH-producing tumor
How is hypothyroidism caused
Inflammatory/ autoimmune disease (hashimoto disease)_ antibodies attacking specific thyroid cellular components (e.g. thyroglobulin), causing gland damage
Defective hypothalamic and pituitary function causing insufficient thyrotropin secretion for normal stimulation of thyroid gland
Dietary iodine deficiency
Graves’ disease
Highly characteristic symptom of weight loss despite increased intake of food, increased heat production causes excessive sweating, greater intake of water, trouble with heart rate
difficulty in swallowing or breathing due to compression of the esophagus or trachea by the enlarged thyroid gland (goitre)
Periorbital edema disagjosed by an elevated serum free and total t3 or t4 level
Treatment of hyperthyroidism
Surgery
Partial or complete removal of gland obstructs neck veins and trachea, or if malaginant tumour present
Drugs
1) thioureylene (also called thiourea or thionamide) compounds
2) iodine-containing preparations
3) beta adrenoceptor
Effects of thioureylenes
Orally active- inhibit thyroid hormone synthesis:
I) prevent iodination of tyrosine residues in thyroglobulin- probably by interfering with peroxidase enzyme action
Ii) prevent coupling reactions of monoiodo- and di-iodotyrosines
Iodine-containing preparations
Radio iodine
Major method of treating hyperthyroidism
Taken orally as capsules of radioactive sodium iodide - radio iodine in blood accumulates in thyroid gland
Produces a-rays mainly b-particles
Used as single administration
Beta adrenoreceptor antagonists
Propranolol usually
No direct effect on thyroid hormone synthesis, release etc
treatment of hypothyroidism
hypothyroid individuals have weight gain despite poor appetite, cold intolerance, constipation and lethargy
synthetic T3, T4 used as replacement therapy
t4, first choice daily oral tablets, initial build-up to maximum effects takes several days because initially absorbed t4 molecules bind reversibly to blood plasma proteins; need these binding sites to become saturated
what is the source and transport of T3 in the brain
t4 enters a glial cell and is converted to T3 by the deindinase. T3 exits the cell and is transported into a neuron via MCT8. Inside the neuron, it enters the nucleus, binding TR, or is inactivated to T2 by D3 deiodinase.
MCT8 mutations
located on the x chromosome
males:
one copy
mutations result in allan-herndon-dudley syndrome.
affected males have abnormal plasma TH concentrations and neurological abnormalities.
females:
two copies
