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Semester 1 > Metabolism S9 - The Thyroid Gland > Flashcards

Metabolism S9 - The Thyroid Gland Flashcards

1
Q

Describe the location of the thyroid gland

A
  • Located in the neck anterior to the lower larynx and upper trachea
  • It is inferior to the thyroid cartilage
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2
Q

There are two major cells in the thyroid gland, what are they?

A
  • Follicular cells - Arranged into follicles separated by connective tissue. The follicle is spherical surrounded by the follicular cells surrounding a central space containing colloid (protein)
  • Parafollicular (C-cells) - found in the connective tissues surrounding the follicle
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3
Q

The thyroid gland has a butterfly shape with two lateral lobes joined by a central ______

A

Isthmus

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4
Q

Two nerves lie in close proximity to the thyroid gland which are at risk during thyroid removal. What are they?

A
  • Recurrent laryngeal
  • External branch of the superior laryngeal
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5
Q

How vascularised is the thyroid gland?

A

Very 3 arteries/veins supplying it - (superior, middle and inferior thyroid)

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6
Q

What 3 hormones does the thyroid gland produce and from where?

A

Thyroxine (T3) and triiodothyronine (T4) from the follicular cells

Calcitonin - parafollicular cells

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7
Q

What amino acid is T3 and T4 derived from?

A

tyrosine

iodine added

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8
Q

Outline the basic synthesis of T3 and T4 in thyroid follicles

A
  • Transport of iodide into the follicular cells against a concentration gradient
  • Synthesis of a tyrosine rich protein (thyroglobulin in follicular cells
  • Secretion of thyroglobulin into the lumen of the follicle
  • Oxidation of iodide to produce iodinating species
  • iodination of the side chains of tyrosine residues in thyroglobulin to form MIT (mono-iodotyrosine) and DIT (di-iodotyrosine)
  • Coupling of MIT and DIT = T3
  • Coupling DIT with DIT = T4 - T3 & T4 residues are produced in the ratio of 1:10
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9
Q

Where is T3 and T4 stored?

A

Extracellular in the lumen of the follicle The amounts stored are considerable and would last for several months at normal rates of secretion

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10
Q

How is T3 and T4 secreted?

A
  • Thyroglobulin (with iodinated side chains) taken into follicular cells by endocytosis
  • Proteolytic cleavage of thyroglobulin releasing T3 and T4
  • These diffuse from the follicular cells into the circulation
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11
Q

How are the levels of T3 and T4 secretion regulated?

A
  • T3 and T4 secretion are under the control of the hypothalamus and anterior pituitary gland
  • hypothalamus - Thyrotropin-releasing hormone (TRH)
  • TRH influenced by levels of T3 and T4 (negative feedback)
  • TRH travels in the HYPOTHALAMIC/PITUITARY PORTAL SYSTEM to stimulate the secretion of thyroid stimulating hormone (TSH)
  • TSH released from the thyrotrophs in the anterior pituitary which travels in the blood to affect follicular cells of thyroid gland
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12
Q

List the hierarchy of T3 and T4 control

A

Thyrotropin-releasing hormone (TRH)

Thyroid stimulating hormone (TSH)

T3 andT4 release

(T3 and T4 negatively feedbacks on both TRH (long-loop inhibition) and TSH (short-loop inhibition ))

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13
Q

What stimulates the release or thyrotropin-releasing hormone?

A
  • Stress
  • Fall in temperature
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14
Q

Where is thyroid stimulating hormone released from?

A

The thyrotropes in the anterior pituitary

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15
Q

Outline the actions of TSH

A
  • TSH interacts with receptors on the surface of follicular cells and stimulates all aspects of of synthesis and secretion of T3 and T4
  • TSH also exerts a trophic effect on the thyroid, increasing vascularity, size and number of follicle cells
  • This is what leads to goitre
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16
Q

What effects do T3 and T4 have in the body?

A
  • Increase the metabolic rate of tissues
  • Stimulate glucose uptake
  • Stimulates mobilisation and oxidation of fatty acids
  • Stimulate protein metabolism
  • important role in growth (see other question) The effects are generally catabolic leading to an increase in BMR, heat production and increased oxygen consumption
17
Q

How are T3 and T4 carried in the blood?

A
  • They are hydrophobic molecules and are transported bound to proteins:

Thyroxine binding globulin, pre-albumin and albumin Only a small amount left unbound

18
Q

What effect does increased levels of oestrogen during pregnancy have on T3 and T4?

A
  • Oestrogen increases the synthesis of thyroxine binding globulin
  • Less T3 and T4 in solution
  • Feeds back with increased levels of TRH and TSH
  • Free T3 and T4 return to normal levels but the total amount in the blood is increased
19
Q

Does T3 or T4 have a shorter half life?

A

T3 = 2 days

T4 = 8 days

20
Q

What role does T3 and T4 play in growth?

A

The CNS is particularly sensitive:

  • Development of cellular processes of nerve cells
  • Hyperplasia of cortical neurones and myelination of nerve fibres (In the absence of thyroid hormones from birth to puberty the child remains mentally and physically retarded (CRETINISM)
  • Directly effect bone mineralisation
  • Increase synthesis of heart protein
21
Q

In an adult, what does lack of thyroid hormone lead to?

A
  • Poor concentration
  • Poor memory
  • Lack of initiative
22
Q

Outline the mechanism of action for T3 and T4

A
  • Cross the plasma membrane of target cells and interact with high affinity receptors located in the nucleus and possibly mitochondria
  • The receptors have a 10-fold greater affinity for T3 than T4
  • Binding unmasks the DNA binding domain
  • When DNA binds, this increases the rate of transcription of specific genes that are translated into proteins
  • Protein synthesis stimulates oxidative energy metabolism
23
Q

Outline T4 to T3 conversion and describe why it is important

A
  • Important mechanism for regulating the amount of active hormone in cells as T3 is 10 times more active
  • Removal of T4’s 5’ iodide yield normal functioning T3
  • Removal of T4 3’ iodide yield an inactive reverse T3 (rT3) rT3 can bind to thyroid hormone receptors without stimulating them, but blocks the effect of T3
24
Q

What is the most common form of hypothyroidism?

A

Hashimoto’s disease Affecting around 1% of the population, mainly women

25
Q

What is the pathology of Hashimoto’s disease?

A
  • An autoimmune disease
  • Destruction of thyroid follicles OR
  • Production of an antibody that blocks the TSH receptor on follicle cells preventing them from responding to TSH
26
Q

How are sufferer’s of Hashimoto’s disease treated?

A
  • Oral thyroxine
27
Q

What are the possible signs and symptoms of hypothyroidism in adults?

A
  • Cold intolerance
  • Weight gain
  • Tiredness and lethargy
  • Bradycardia
  • Neuromuscular system - weakness, muscle cramps and cerebellar ataxia (clumsiness of movement)
  • Dry and flaky skin
  • Alopecia
  • Voice is deep and husky
28
Q

What is the most common form of hyperthyroidism?

A

Graves’s Disease Affects 1% of population, mainly women

29
Q

What is the pathology of Grave’s disease?

A
  • An autoimmune disease
  • Thyroid stimulating immunoglobulin (TSI) antibodies produced
  • TSI stimulate TSH receptors on follicle cells resulting in increased production and release of T3 and T4
  • TSH levels fall due to the negative feedback loop
  • TSH levels do not affect thyroid hormone release since stimulus is TSI
30
Q

How is Grave’s disease treated?

A
  • Carbimazole

Inhibits the thyroid peroxide enzyme that prevents coupling and iodination of tyrosine residues on the thyroglobulin

  • total removal of thyroid leaving parathyroid behind
31
Q

What are the possible signs and symptoms of hyperthyroidism?

A
  • Heat intolerance, increased oxygen consumption and increased BMR
  • Weight loss
  • Physical and mental hyperactivity
  • Tachycardia
  • Intestinal hyper mobility
  • Skeletal and cardiac myopathy giving rise to tiredness, weakness and breathlessness
  • Osteoporosis due to increased bone turnover and preferential resorption
32
Q

What role does calcitonin have?

A

Reduces blood calcium levels by inhbiting the actions of osteoclasts

Opposite of parathyroid hormone

33
Q

What is found in the lumen of follicles in the thyroid?

A

Thyroglobulin rich colloid

34
Q

Why does T4 have a greater half life than T3

A

Higher affinity for transport proteins so remains in circulation for longer However T3 is more biologically active

35
Q

Describe the structure of TSH

A
  • Glycoprotein hormone
  • 2 subunits (alpha, beta)
  • Released in low amplitude pulses twice per day
  • Circadian rhythm
36
Q

Outline the differences you would expect to see in the blood test results of a patient with hyperthyroidism and one with hypothyroidism

A

Hyperthyroidism- high free T4, low TSH

Hypothyroidism- low free T4, high TSH

Semester 1 (37 decks)

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