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Thyroid Flashcards

0
Q

What type of gland is the thyroid?

A

-Ductless alveolar endocrine

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1
Q

Where is the thyroid located?

A

-In the neck, situated in front of the lower larynx and upper trachea and wraps around the trachea below the cricoid cartilage

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2
Q

What shape is the thyroid gland?

A

-Butterfly shape with two lateral lobes joined by a central isthmus

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3
Q

What is the usual size of the thyroid?

A

-2-3cm in diameter

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4
Q

What two cell types are found in the thyroid?

A
  • Follicular

- Parafollicular (c-cells)

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5
Q

How are follicular cells arranged?

A

-In numerous functional units called follicles separated by connective tissue

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6
Q

What is the structure of the follicles?

A

-Spherical, lined with epithelia surrounding a colloid filled centre

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7
Q

Where are the parafollicular cells located in the thyroid?

A

-In the connective tissue

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8
Q

How does the thyroid receive/drain its blood supply?

A
  • Superior/inferior thyroid arteries
  • Drainage via superior, middle and inferior veins
  • Rich lymphatic system
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9
Q

What are the three hormones produced by the thyroid?

A
  • T3->triiodothyronine
  • T4-> thyroxine
  • Calcitonin
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10
Q

Where is calcitonin produced?

A

-Parafollicular cells

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11
Q

What are T3 and T4 synthesised from?

A

-Tyrosine with the addition of iodine

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12
Q

Are T3 and T4 water-soluble or lipid-soluble?

A

-Lipid-soluble

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13
Q

Where are T3 and T4 produced?

A

-Follicular cells

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14
Q

Describe iodine uptake into the follicular cells

A
  • Follicular epithelial cells contain transporters
  • These transporters create an iodide trap at the basolateral membrane by actively pumping Na+ into the extra cellular fluid creating a Na+ gradient between the ECF anf the follicular cells
  • As Na+ moves back into the cell I- is coupled with it
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15
Q

What effect do the transporters have on the follicular epithelia cell membrane?

A

-Cause it to be polarised

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16
Q

What is iodine uptake dependant upon?

A

-Iodine from the diet

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17
Q

How and where does iodine become activated?

A
  • Activation occurs at the apical membrane

- Activated into a reactive form by a peroxidase enzyme

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18
Q

What happens to the iodine in follicular epithelial cells once it has become activated?

A

-Associates with thyroglobulin which is rich in tyrosine and Iodine is coupled to the tyrosine and stored as colloid

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19
Q

Where is thyroglobulin synthesised?

A
  • Synthesised in ribosomes

- Glycosylated in ER and packaged into secretory vessels by golgi

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20
Q

Where is thyroglobulin stored?

A

-Vesicles in follicular cells

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21
Q

What modifications occur to the thyroglobulin:iodine complex in the lumen of the follicle in order to produce T3 and T4?

A
  • Tg:I complex oxidised to produce iodinating species
  • Iodination of the side chain residues of tyrosine in thyroglobulin forms mono-iodotyrosine and di-iodotyrosine
  • Coupling of di-iodotyrosine with mono-iodotyrosine and di-iodotyrosine produced T3 and T4 respectively
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22
Q

Where are T3 and T4 stored?

A

-Extracellularly in the lumen of the follicles as part of thyroglobulin

23
Q

How are T3 and T4 secreted?

A
  • Thyroglobulin taken up into epithelial cells from lumen by endocytosis
  • Proteolytic cleavage of thyroglobulin releases T3 and T4 which diffuse from the epithelial cells into the circulation
24
How are T3 and T4 transported?
- Lipid-soluble and hydrophobic thus transported in the blood bound to proteins, thyronine-binding protein and albumin - <1% is free in solution which is the biological active form
25
Is T3 or T4 in greater free proportions and why? What effect does this have on the hormone?
- T3 as it has a lower affinity for thyronine-binding hormone - Consequently T3 has a shorter half-life
26
What happens to T3 and T4 levels during pregnancy?
- Relative increase as during pregnancy thyronine-binding globulin production is increased, resulting in a decrease in free T3/T4 - Due to negative feedback TRH and TSH increase, stimulating the thyroid to produce more T3 and T4
27
How is the activity of the thyroid gland controlled?
- Negative feedback from the HPA - Hypothalamus produces thyrotropin releasing hormone, released into the HPA portal, under the influence of circulating T3/T4 levels, stress and temperature - TRH stimulates the anterior pituitary to secrete thyroid stimulating hormone by exocytosis from the thyrotrophs as there is a resultant increase in intracellular calcium in response to TRH - TSH travels in the blood to effect the follicular cells of the thyroid - TSH production also directly effected by circulating T3 and T4
28
What effect does TSH have on thyroid follicular cells?
-Interactes with receptors on the surface of follicular cells and stimulates all aspects of synthesis and secretion of T3 and T4
29
Besides hormone production, what other effect does TSH have on the thyroid gland? What does this effect produce?
- Trophic effect that causes an increase in the size and number of follicular cells - Produces a goitre (enlarged thyroid gland) which may or may not be overactive
30
Why is more T4 produced than T3?
-T3 is more potent that T4 but has a shorter half-life, thus is it beneficial to secrete more T4 and convert to T3 as needed
31
Where and how does conversion of T4->T3 occur?
-In the peripheral tissues by a deiodination reaction
32
How is T3 and T4 degraded?
-Complete deiodination in the liver and kidneys
33
What effect do T3 and T4 have on BMR?
-Increase BMR by increase number and size of mitochondria increases O2 consumption and heat production Increases nutrient utilisation
34
What metabolic pathways do T3 and T4 stimulate?
- Mostly catabolic | - Increase lipolysis, glycolysis, glycogenolysis and proteolysis
35
How do T3 and T4 promotr normal growth/development of tissues?
-Increase synthesis of specific proteins
36
What effect do T3 and T4 have on the nervous system?
- Increase responsiveness of tissues to SYMPATHETIC nervous system (specifically, noradrenaline) increasing the speed of reflexes - Increase myelination of nerve fibres and development of neurones - Increase metal activity (alertness, emotional tone, memory)
37
What effect do T3 and T4 have on the cardiovascular system?
- Increase cardiac output | - Has direct effects on heart muscle and potentiates the effects of noradrenaline
38
What effect do T3 and T4 have on skin and subcutaneous tissue?
-Increase turnover of proteins and glycoproteins
39
What effect do T3 and T4 have on bone?
-Affects mineralisation
40
What is the mechanism of action of T3 and T4?
- Lipid-soluble so can cross pm - Interacts with specific high-affinity receptors located in the nucleus - Hormone:receptor complex undergoes conformational change exposing DNA-binding domain - Interaction of Hormone:receptor with DNA - Increases transcription of specific genes for enzymes and structural proteins
41
What effects does hypothyroidism have in the newborn? Describe the effects of this disease
- Cretinism - Severe mental retardation due to failure of CNS development - Diminished linear growth due to effected bone mineralisation and metabolism - Delayed sexual development
42
Is cretinism reversible?
-If treated within a few weeks
43
What is hypothyroidism?
-Undersecretion of thyroid hormones
44
What are the signs and symptoms of hypothyroidism in an adult?
- Cold intolerance with decreased perspiration - Mild weight gain - Bradycardia (deacreased cardiac output) - Constipation - Mood swings (anxious/depressed) - Slowing in cognitive ability (memory/concentration) - Dry skin, brittle nails, hair loss - Tiredness and lethargy (reduced BMR)
45
What is the major cause of hypothyroidism?
-Hashimoto's disease
46
What causes hashiomoto's disease?
-Autoimmune destruction of the thyroid follicles or production of antibodies with block TSH receptors on cells resulting in no T3 or T4 production
47
How is hypothyroidism treated?
-Oral T4
48
Besides hasimoto's disease, what are other causes of hypothyroidism?
- Post-surgery - Iodine deficiency - Rare inborn errors - Secondary to lack of TSH (pituitary adenoma)
49
What is hyperthyroidism?
-Oversecretion of thyroid hormones
50
What are the signs and symptoms of hyperthyroidism in the adult?
- Heat intolerance (increased perspiration, moist hands) - Weight loss (increased lipolysis and proteolysis) - Tachycardia (increased cardiac output, often irregular) - Increased bowel movements and appetite - Nervousness, irritability and emotionally labile - Hyper-reflexivity (possible tremor of outstretched hand) - Exophtamalos (buldging of the eyes)
51
What is the major cause of hyperthyroidism?
-Grave's disease
52
What is the cause of grave's disease?
-Autoimmune disease by production of antibody that stimulates TSH receptor on follicular cells increasing T3/T4 production
53
What are the treatments of hyperthroidism?
- Carbizamole -> inhibits incorporation of iodine into thyroglobulin - Radioactive iodine - Surgery
54
Besides Grave's disease, what are other causes of hyperthyroidism?
- Ectopic thyroid tissue - Thyroid carcinoma - Excess iodine - Other autoimmune diseases eg toxic multinodular goitre and solitary toxic adenoma

Metabolism (14 decks)

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