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
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
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
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)
5
Q
Name 3 hormones produced by the thyroid gland
A
- Thyroxine T4
- Triiodothyronine T3
- Calcitonin (from C cells)
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
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)
8
Q
How are thyroid hormones stored within the gland?
A
EXTRACELLUARLY in the lumen of the thyroid follicles
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
10
Q
Describe the location of the thyroid gland
A
- Base of neck
- In front of the LOWER LARYNX and the UPPER TRACHEA
11
Q
Where exactly in the hypothalamus is TRH released from?
A
Dorsomedial nucleus
12
Q
What factors increase the release of TRH?
A
- Low circulating levels of T3 and T4
- Stress
- Temperature decrease
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
14
Q
TSH follows a diurnal rhythm. What is meant by this?
A
- Increased levels at night
- Decreased levels at morning
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
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)
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
Why is the production ratio of T3:T4 1:10?
- 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
Describe how HASHIMOTO'S DISEASE occurs
- 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
Explain how Hashimoto's disease can be treated
- 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
Describe how GRAVE'S DISEASE occurs
- 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
Describe the action of carbimozole and explain how this is used to treat hyperthyroidism (Grave's)
- 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
What is the role of thyroid peroxidase?
- Conversion of iodide to iodinating species
| - Iodination of Tyr residues on thyroglobulin to produce T3 and T4
31
List the common signs and symptoms of hyperthyroidism
- 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
What are the signs and symptoms of hypothyroidism?
- 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
Explain why a patient with hyperthyroidism may get osteoporosis
Increased bone turnover and preferential reabsorption of calcium
34
Explain why a patient with hyperthyroidism may experience tiredness, muscle weakness and breathlessness
- Increased heart rate (tachycardia) may cause palpitations (irregular heartbeat)
- Increased myopathy of skeletal and possibly cardiac muscle
35
A thyroid function test (TFT) showed an increase in free T4 but a decrease in TSH. What can you infer from these results?
Hyperthyroidism
36
How could you detect a goitre?
- Visible
- Ultrasound
- Listen in neck for palpitations (increased blood supply to gland)
37
Explain why newborns are tested for hypothyroidism at birth
- 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
Exophthalmos (bulging of eyes) is rare but can occur in people with thyroid disorders. What causes this?
Accumulation of adipose tissue and fluid behind eyeball causing them to 'bulge' out
39
Describe the effects of T3 and T4 on the nervous system
- Increased myelination of nerve fibres and development of neurones
- Increased speed of reflexes
- Increased mental awareness and activity
40
Why might an increase in thyroid hormone cause an increase in heart rate?
- Increases cardiac output
| - Increases responsiveness of cardiac muscle receptors to neurotransmitters such as noradrenaline
41
Why might a patient with hypothyroidism have dry flaky nails and saggy skin?
Decreased protein synthesis and turnover of collagen and keratin which are essential in maintaining healthy skin and nails
42
Why does T4 has a longer half life in the circulation than T3?
Binds more tightly to transport proteins so is less likely to be degraded
