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Metabolism > Session 10 > Flashcards

Session 10 Flashcards

0
Q

When is the thyroid gland visible and palpable?

A
  • When it is enlarged (goitre)
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1
Q

Where is the thyroid gland located?

A
  • In the neck in the front of the lower larynx and upper trachea
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2
Q

What else is near to the thyroid gland?

A
  • 2 nerves (recurrent laryngeal and external branch of the superior laryngeal)
  • Highly vascularised with 3 arteries and veins supplying and draining it (superior, middle and inferior thyroid arteries and veins)
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3
Q

What is the structure of the thyroid gland?

A
  • Butterfly shape
  • 2 lateral lobes connected by a central isthmus
  • Usually 2-3 cm and 15-20g
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4
Q

What are the main cells types of the thyroid gland?

A
  • Follicular (arranged in follicles separated by connective tissue)
  • Parafollicular (C-cells) (found in the connective tissue)
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5
Q

What hormones are produced by the follicular cells of the the thyroid gland?

A
  • Throxine (T4)
  • Tri-idothyronine (T3)
  • Small molecules derived from amino acid tyrosine with the addition of atoms of iodine
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6
Q

What hormone is produced by the parafollicular cells of the thyroid gland?

A
  • Calcitonin

- Polypeptide hormone

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7
Q

How are T3 and T4 synthesised in the thyroid follicles?

A
  • Transport of iodine into epithelial cells against a concentration gradient
  • Synthesis of a tyrosine rich protein (thyroglobulin) in the epithelial cells
  • Secretion by exocytosis of thyroglobulin into the lumen of the follicle
  • Oxidation of iodine to produce an iodinating species
  • Iondination of the side chains of tyrosine residues in the thyroglobulin to form MIRA (mono-iodotyrosine) and DIT (di-iodotyrosine)
  • Coupling of DIT with MIT/DIT to form T3/T4 respectively within the thyroglobulin
  • T3 and T4 residues are produced in the ratio of 1:10
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8
Q

How are T3 and T4 stored?

A
  • Extracellularly in the lumen of the follicles as part of thyroglobulin molecules
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9
Q

How are T3 and T4 secreted?

A
  • Thyroglobulin is take into epithelial cells by Endocytosis from the lumen of the follicles
  • Thyroglobulin undergoes proteolytic cleavage to release T3 and T4
  • T3 and T4 diffuse from the epithelial cells into the circulation
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10
Q

What controls T3 and T4 synthesis and secretion?

A
  • Hypothalamus: releases Thyrotrophin-releasing hormone (TRH)
  • Anterior pituitary gland: releases Thyroid Stimulating Hormone (stimulated by TRH) and affects follicular cells of thyroid gland
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11
Q

What is TRH secretion influenced by?

A
  • Circulating levels of T3 and T4 (negative feedback)
  • Stress (increases release)
  • Temperature (fall increases release)
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12
Q

What is the structure of TSH?

A
  • Glycoprotein consisting of 2 non-covalently linked subunits
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13
Q

When is TSH a released?

A
  • Released in low-amplitude pulses

- Diurnal rhythm: higher levels at night, lower levels in the early morning

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14
Q

What are the actions of TSH on follicle cells and how?

A
  • Interacts with cell surface receptors
  • Stimulates synthesis and secretion of T3 and T4
  • Has trophic effects on the cell -> increased vascularity, size and number of cells
  • Can result in an enlarged thyroid (goitre) that may or may not be active
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15
Q

How are T3 and T4 transported?

A
  • Are hydrophobic
  • Transported in the blood bound to proteins (thyronine binding globulin, pre-albumin and albumin)
  • Only a small amount is free in solution
  • Free hormone is biologically active
  • T3 has a shorter half-life and a higher free percentage than T4 as T3 has a slightly lower affinity for transport proteins
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16
Q

What happens to T3 and T4 levels during pregnancy?

A
  • Oestrogens increase synthesis of thyronine binding globulin -> flat in T3 and T4 in the circulation as more is bound
  • Fall in T3 and T4 removes inhibitory feedback in pituitary and hypothalamus -> secrete more TRH and TSH -> more T3 and T4 are secreted
  • Amount of free T3 and T4 returns to normal, but total amount in the blood increases
17
Q

What types of effects does T3 and T4 have in tissues?

A
  • General effects on metabolic activity

- Specific effects

18
Q

What general effects do T3 and T4 have on tissues?

A
  • Increase metabolic rate
  • Stimulate glucose uptake and metabolism
  • Stimulates fatty acid mobilisation and oxidation
  • Stimulates protein metabolism
  • Metabolism effects are usually catabolic -> increase in BMR, heat production and oxygen consumption
19
Q

How are T3 and T4 important in normal growth and development?

A
  • Effects on physical growth related to metabolic effects on tissues
  • Also specific effects eg bone mineralisation, and increased synthesis of heart muscle protein
20
Q

What is T3 and T4 required for in the development of the CNS?

A
  • Development of cellular processes of nerve cells
  • Hyperplasia of cortical neurones
  • Myelination of nerve fibres
21
Q

What happens in relation to the CNS is the thyroid hormones are not present?

A
  • Cretinism: mental and physical retardation if thyroid hormones are not present from birth to puberty
  • Damage is irreversible a few weeks after birth if deficiency is not corrected (all newborns have their thyroid function checked after birth)
22
Q

What is lack of thyroid hormones characterised by in adults?

A
  • Poor concentration
  • Poor memory
  • Lack of initiative
23
Q

What are the indirect actions of T3 and T4?

A
  • Related to important interactions with other hormones and neurotransmitters
  • Stimulate hormone and neurotransmitter receptor synthesis in a variety of tissues eg heart muscle, GI tract
  • Increased responsiveness in these tissues to regulatory factors
  • eg in heart muscle -> tachycardia; in the GI tract -> increased motility
24
Q

With which hormones do T3 and T4 have a permissive role?

A
  • FSH, LH and ovulation fails to occur in the absence of thyroid hormones
25
Q

What is the mechanism of action for T3 and T4?

A
  • Cross plasma membrane of target cells
  • Interact with specific high affinity receptors in the nucleus and possibly mitochondria
  • Receptors have a 10-fold greater affinity of T3 and T4
26
Q

What happens when T3 binds to the hormone-binding domain of receptors?

A
  • Conformational change in receptor that unmasks DNA-binding domain
  • Interaction of hormone-receptor complex with DNA (nuclear or mitochondrial) increase the rate of transcription of specific genes that are then translated into protein
27
Q

What does increased rate of protein synthesis do in target cells?

A
  • Stimulates oxidative energy metabolism required for protein synthesis
  • Also increases production of specific functional proteins -> increase cell activity and increased demand for energy
28
Q

How can T4 be converted to T3?

A
  • Removal of the 5’-iodide
29
Q

Why is conversion of T4 to T3 important?

A
  • Regulation of active hormone in cells as T3 has x10 activity of T4
30
Q

What does the removal of 3’-iodide from T3 do?

A
  • Produces inactive reverse T3 (rT3)

- Binds to thyroid hormone receptors without stimulating them and blocks the effect of T3

31
Q

What are clinical problems caused by?

A
  • Hyperthyroidism (too much physiologically active thyroid hormones)
  • Hypothyroidism (to little physiologically active thyroid hormones)
32
Q

What is the most common form of hypothyroidism?

A
  • Hashimotos’ disease
  • Autoimmune disease -> destruction of thyroid follicles or production of an antibody that blocks TSH receptor on follicle cells (prevents them responding to TSH)
  • Treated with oral thyroxine
33
Q

What are other causes of hypothyroidism?

A
  • Post-surgery
  • Radioactive iodine
  • Anti-thyroid drugs
  • Secondary (lack of TSH)
  • Congenital
  • Iodine deficiency
34
Q

What is the most common form of hyperthyroidism?

A
  • Grave’s disease
  • Autoimmune disease -> antibodies that stimulate TSH receptors on follicle cells are produced -> increased production and release of T3 and T4
  • Treated with carbimazole drug (inhibits thyroid peroxidase enzyme -> prevents coupling and iodination of tyrosine on thyroglobulin)
35
Q

What are other causes of hyperthyroidism?

A
  • Toxic (overproducing T3/T4) multi-nodular goitre
  • Excessive T3/T4 therapy
  • Excess iodine - amiodarone
  • Thyroid carcinoma (99% don’t cause hyper/hypothyroidism)
  • Ectopic thyroid tissue
36
Q

What are the signs and symtoms of hypothyroidism in adults?

A
  • Cold intolerance and reduced BMR
  • Weight gain
  • Tiredness and lethargy
  • Bradycardia
  • Neuromuscular system: weakness; muscle cramps; cerebellar ataxia (clumsiness of movement)
  • Skin is dry and flaky
  • Alopecia
  • Voice is deep and husky
37
Q

What are the 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 -> tiredness; weakness; breathlessness
  • Osteoporosis due to Increased bone turnover and preferential resorption (osteoclasts > osteoblasts)
40
Q

What happens to levels of free T4 and TSH in hypothyroidism?

A
  • ⬇️ free T4

- ⬆️ TSH

41
Q

What happens to levels of free T4 and TSH in hyperthyroidism?

A
  • ⬆️ free T4

- ⬇️ TSH

Metabolism (11 decks)

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