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ESA1 - Metabolism > Thyroid Gland & Function > Flashcards

Thyroid Gland & Function Flashcards

1
Q

What is a goitre?

A
  • Swelling at base of neck due to ENLARGED THYROID GLAND

- Can be present in both hyper and hypo thyroidism

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2
Q

Describe the structure of the thyroid gland

A
  • Butterfly shaped
  • Two lateral lobes with a central ISTHMUS
  • Normally 2-3cm in width and weights 15-20g
  • Follicular epithelial cells arranged encircle a central colloid forming a FOLLICLE
  • Parafollicular (C cells) dispersed throughout connective tissue
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3
Q

How is a thyroid follicle arranged?

A
  • Follicular epithelial cells (simple cuboidal) encircle a central lumen called a COLLOID
  • Colloid is rich in THYROGLOBULIN
  • Follicles are separated by connective tissue
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4
Q

Describe the blood supply and nerve arrangement of the thyroid gland

A
  • Thyroid gland is HIGHLY VASCULARISED with 3 arteries and 3 veins supplying and draining blood (SUPERIOR, MIDDLE, INFERIOR)
  • 2 nerves lie in close proximity; the RECURRENT LARYNGEAL and the external branch of the SUPERIOR LARYNGEAL (supply larynx and are involved in speech)
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5
Q

Name 3 hormones produced by the thyroid gland

A
  • Thyroxine T4
  • Triiodothyronine T3
  • Calcitonin (from C cells)
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6
Q

Explain how T3 and T4 are formed from tyrosine inside the follicles of the thyroid gland

A
  • Transport of IODIDE into follicular cells across basalateral membrane
  • Synthesis of THYROGLOBULIN from Tyrosine inside follicular cells
  • Both iodide and thyroglobulin are secreted out of the cell into the colloid (lumen of follicle) by EXOCYTOSIS
  • Iodide OXIDISED to form IODINATING SPECIES which iodinates thyroglobulin forming MIT and DIT
  • Coupling of MIT/DIT and DIT/DIT form T3 and T4 respectively
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7
Q

How are MIT and DIT involved in the synthesis of T3 and T4?

A
  • MIT mono-iodotyrosine and DIT di-iodotyrosine couple together to form T and T4 molecules
  • MIT + DIT = T3 (3 iodines)
  • DIT + DIT = T4 (4 iodines)
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8
Q

How are thyroid hormones stored within the gland?

A

EXTRACELLUARLY in the lumen of the thyroid follicles

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9
Q

Explain how T3 and T4 are secreted from the follicle into the bloodstream

A
  • Thyroglobulin enters the follicular cells from the colloid via ENDOCYTOSIS
  • Thyroglobulin undergoes PROTEOLYTIC CLEAVAGE releasing T3 and T4
  • T3 and T4 diffuse from the follicular cell into the circulation
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10
Q

Describe the location of the thyroid gland

A
  • Base of neck

- In front of the LOWER LARYNX and the UPPER TRACHEA

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11
Q

Where exactly in the hypothalamus is TRH released from?

A

Dorsomedial nucleus

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12
Q

What factors increase the release of TRH?

A
  • Low circulating levels of T3 and T4
  • Stress
  • Temperature decrease
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13
Q

Explain how TRH causes the secretion of T3 and T4 from the thyroid

A
  • TRH stimulates secretion of TSH from thyrotropes in anterior pituitary
  • TSH travels in blood to follicular cells and binds to basalateral membrane, stimulating the release of T3 and T4 from the colloid into the blood
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14
Q

TSH follows a diurnal rhythm. What is meant by this?

A
  • Increased levels at night

- Decreased levels at morning

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15
Q

Explain how an iodine deficiency can cause a goitre

A
  • Decreased production of T3 and T4
  • Low concentrations of T3 and T4 are detected in hypothalamus causing increase in secretion of TRH thus increased secretion of TSH from anterior pituitary
  • TSH has trophic effects on follicular cells causing hypertrophy, hyperplasia and increased vascularisation of thyroid resulting in an enlarged gland
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16
Q

Explain how T3 and T4 are transported in the bloodstream

A
  • LIPID SOLUBLE so must be bound to proteins
  • ~99% bound to THYRONINE BINDING GLOBULIN (TBG), pre-albumin or albumin
  • ~1% free in solution (free hormone is biologically active)
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17
Q

What is the effect of OESTROGEN on circulating levels of T3 and T4?

A
  • Oestrogen stimulates synthesis of TBG
  • Decrease in amount of free circulating T3 and T4 as more is bound
  • Detected in hypothalamus and pituitary so increased secretion of TRH and TSH
  • More T3 and T4 produced so increased amount of free T3 and T4 in circulation (TOTAL CONCENTRATION HAS INCREASED as there is more bound as well as unbound)
18
Q

Explain the actions of T3 and T4 which allow an increase in the basal metabolic rate BMR of cells

A
  • Action is mainly CATABOLIC
  • Stimulates glucose uptake and metabolism
  • Stimulates mobilisation and oxidation of fatty acids
  • Stimulates protein metabolism
  • Increased oxygen consumption
  • Increased heat production
19
Q

Explain why an absence of thyroid hormone at birth may lead to cretinism

A
  • Required for the development of the CNS
  • Myelination of nerve fibres, hyperplasia of cortical nerves
  • Must be treated immediately to prevent irreversible damage such as mental and physical retardation
20
Q

Describe how an increase in thyroid hormones T3 and T4 may lead to tachycardia

A
  • T3 and T4 have indirect effects on hormone and neurotransmitter receptor synthesis on a variety of tissues e.g. heart muscle
  • Can increase the responsiveness of heart muscle to regulatory factors
21
Q

Describe the action of T3 on the nucleus of cells

A
  • Binds to specific receptors and causes a conformational change that unmasks the DNA-binding domain
  • Hormone receptor complex binds to DNA and INCREASES RATE OF TRANSCRIPTION of specific genes which are then translated into proteins
22
Q

Explain how an increase in protein synthesis can lead to an increase in overall cell activity

A
  • Increases amount of specific functional proteins so increases cell activity
  • Increased demand for energy for various cell processes (e.g. Transport, protein synthesis) therefore increased oxidative metabolism to produce more ATP
23
Q

Describe how the amount of active thyroid hormone is regulated in cells

A
  • T4 converted to T3 by removal of 5’ iodide
  • T3 has 10x activity of T4
  • T3 regulated by removal of 3’ iodide from T4 producing inactive REVERSE rT3 which can bind to T3 receptors but does not stimulate them, so blocks binding site for T3
24
Q

Explain why a lack of thyroid hormones may lead to poor concentration in adults

A
  • Decreased stimulation of neurotransmitter receptor synthesis
  • Decreased responsiveness of tissues to neurotransmitters (brain)
25
Q

Why is the production ratio of T3:T4 1:10?

A
  • T3 is the active form of T4 and has a shorter half life
  • T4 binds more tightly to transport proteins and lasts longer in the blood
  • T4 is converted to T3 once it enters the target cell
26
Q

Describe how HASHIMOTO’S DISEASE occurs

A
  • Most common form of HYPOTHYROIDISM
  • AUTOIMMUNE
  • Antibodies block TSH receptor site on follicular cells so TSH cannot bind
  • No production of T3/T4
  • Increased TSH secretion due to negative feedback mechanisms
  • Can result in destruction of thyroid follicles
27
Q

Explain how Hashimoto’s disease can be treated

A
  • Oral thyroxine T4
  • Increases concentration of thyroid hormones in blood
  • Decreases production of TSH to normal
  • Dose is adjusted based on patient’s signs and symptoms and TSH levels
28
Q

Describe how GRAVE’S DISEASE occurs

A
  • Most common form of HYPERTHYROIDISM
  • AUTOIMMUNE
  • Antibodies TSI bind to TSH receptors leading to increased production and secretion of T3/T4
  • TSH levels fall due to negative feedback of high concentrations of thyroid hormones in circulation
29
Q

Describe the action of carbimozole and explain how this is used to treat hyperthyroidism (Grave’s)

A
  • Inhibits THYROID PEROXIDASE (Iodide -> Iodinating species)
  • Prevents iodination and coupling of Tyr residues
  • Less T3 and T4 produced so circulating thyroid hormone levels decrease
30
Q

What is the role of thyroid peroxidase?

A
  • Conversion of iodide to iodinating species

- Iodination of Tyr residues on thyroglobulin to produce T3 and T4

31
Q

List the common signs and symptoms of hyperthyroidism

A
  • INCREASED BMR
  • Increased body temperature
  • Tachycardia
  • Weight loss AND increased appetite
  • Mental and physical hyperactivity
  • Increased bowel movements (diarrhoea)
  • Muscle weakness (increased myopathy of skeletal muscle)
32
Q

What are the signs and symptoms of hypothyroidism?

A
  • DECREASED BMR
  • Decreased body temperature
  • Bradycardia
  • Weight gain
  • Poor concentration/low mood
  • Decreased bowel movements (constipation)
  • Tiredness and lethargy
  • Dry and flaky skin and nails
  • Hair loss
  • Deep husky voice
33
Q

Explain why a patient with hyperthyroidism may get osteoporosis

A

Increased bone turnover and preferential reabsorption of calcium

34
Q

Explain why a patient with hyperthyroidism may experience tiredness, muscle weakness and breathlessness

A
  • Increased heart rate (tachycardia) may cause palpitations (irregular heartbeat)
  • Increased myopathy of skeletal and possibly cardiac muscle
35
Q

A thyroid function test (TFT) showed an increase in free T4 but a decrease in TSH. What can you infer from these results?

A

Hyperthyroidism

36
Q

How could you detect a goitre?

A
  • Visible
  • Ultrasound
  • Listen in neck for palpitations (increased blood supply to gland)
37
Q

Explain why newborns are tested for hypothyroidism at birth

A
  • Thyroid hormones have direct effects on bone mineralisation and development of CNS
  • Lack of thyroid hormones can result in mental and physical retardation (CRETINISM)
  • Early detection can prevent this as oral thyroxine can be administered
38
Q

Exophthalmos (bulging of eyes) is rare but can occur in people with thyroid disorders. What causes this?

A

Accumulation of adipose tissue and fluid behind eyeball causing them to ‘bulge’ out

39
Q

Describe the effects of T3 and T4 on the nervous system

A
  • Increased myelination of nerve fibres and development of neurones
  • Increased speed of reflexes
  • Increased mental awareness and activity
40
Q

Why might an increase in thyroid hormone cause an increase in heart rate?

A
  • Increases cardiac output

- Increases responsiveness of cardiac muscle receptors to neurotransmitters such as noradrenaline

41
Q

Why might a patient with hypothyroidism have dry flaky nails and saggy skin?

A

Decreased protein synthesis and turnover of collagen and keratin which are essential in maintaining healthy skin and nails

42
Q

Why does T4 has a longer half life in the circulation than T3?

A

Binds more tightly to transport proteins so is less likely to be degraded

ESA1 - Metabolism (20 decks)

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