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Metabolism 2 PBL > PBL 5 > Flashcards

PBL 5 Flashcards

1
Q

What are the two thyroid hormones

A

Triiodothyronine (T₃) and Thyroxine (T₄)

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2
Q

what do the thyroid hormones do

A

regulate metabolism

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3
Q

what is the main thyroid hormone in the blood

A

T₄ is the main form in the blood (ratio T₄:T₃ is 20:1)

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4
Q

How is T4 converted into to T3

A

T₄ is converted into active T₃ within cells by deiodinases

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5
Q

which is more potent T3 or T4

A

T₃ is 4x more potent

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6
Q

what is thyroid hormone in the blood bound to

A

Most thyroid hormone in blood is protein bound

mainly Thyroxine-binding globulin TBG

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7
Q

free thyroid hormone is…

A

biologically active

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8
Q

How are thyroid hormones produced

A

Iodide trapping: Iodide (I-)moves
into follicular cell through Na+/I-
symporter

I- moves into colloid

I- is oxidised to Iodine (I) by
thyroid peroxidase (TPO)

Meanwhile, thyroglobulin is
synthesised on rough ER and is exocytosed into colloid

Iodine is reactive & iodinates
tyrosyl residues of thyroglobulin (catalysed by TPO) to form MIT
and DIT

The tyrosyl residues pair together

Iodinated thyroglobulin is
endocytosed back into cell

Lysosomes fuse and cause
proteolysis, resulting in formation of T3 & T4

Thyroid hormones are then
released into blood

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9
Q

describe then hypothalamic pituitary thyroid axis

A

Hypothalamus secretes
thyrotropin-releasing
hormone (TRH)

TRH stimulates the Anterior
pituitary to release thyroid
stimulating hormone (TSH)

TSH stimulates T3 and T4
production from the thyroid
gland

  • T3 and T4 loop back and inhibit TRH and TSH when the concentration of T3 and T4 get too high

Negative feedback loop

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10
Q

what is the difference between hyperthyroidism and hypothyroidisms

A

Hyperthyroidism

  • T3 and T4 is risen
  • TSH decreased

hypothyroidism

  • T3 and T4 decreases
  • TSH increases
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11
Q

deiodinase activity varies…

A

Deiodinase activity varies from tissue to tissue

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12
Q

describe how deiodinase activity varies in different tissues

A

Deiodinase 1 = liver & kidney activates T4 🡪 T3

Deiodinase 2 = brain, heart, skeletal muscle activates T4 🡪 T3

Deiodinase 3 = fetal tissue, brain neurones inactivates T3&4

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13
Q

describe the T4 and D2 hormones

A

If T4 levels fall, D2 is upregulated. Elevated levels of T4 will downregulate D2, to protect brain tissue from excess thyroid
hormone.

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14
Q

What is the role of T4 and T3

A

Increases basal metabolic rate
- Increased heat production

Increased triglyceride breakdown, fatty acid
oxidation and cholesterol
- Hypercholerstrolaemia is an indication of
hypothyroidism

Increase insulin dependent entry of glucose into
cells via GLUT4 in the muscles

increase glycogen breakdown and increase gluconeogenesis in the hepatocytes

Increases cardiac output
- Increased contractility, heart rate, and and promotes
vasodilation

Stabilises GI motility and tone
- Imbalances in thyroxine levels causes either diarrhoea
(too much) or constipation (too little)

Ensures normal reproductive physiology
- Imbalances are associated with reduced reproductive
function

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15
Q

What is the role of T4 and T3 in children

A

Essential for growth in children
- Congenital hypothyroidism is tested for in
heel prick test
- Cretinism

Essential for brain development
- Too much thyroid hormone causes anxiety
and nervousness
- Too little thyroid hormone causes sluggish
thinking
- Plays a role in foetal and neonatal brain
development

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16
Q

what are the causes of hypothyroidism

A
  • iodine deficiency - most commenst cause
  • Hashimoto’s thyroiditis
  • post-partum thyroiditis
  • pituitary disease
  • congenital hypothyroidism - cretinism
  • lithium or amiodarone
17
Q

what is hashimotors thyroditisi

A

Autoimmune condition characterised by lymphocytic infiltration of
thyroid gland and anti-TPO and anti-Tg antibodies

18
Q

describe the epidemiology of Hashimoto’s thyroiditis

A

Commonest in the UK

Commonly affects women

Type 2/4 hypersensitivity

19
Q

what are the symptoms of hyothyrodisim

A

Weight gain, obesity – with a low appetite

Cold intolerance, hypothermia

Depressed/low mood/tired/lethargic

Constipation

Dementia

20
Q

what are the signs of hypothyroidism

A

Bradycardic

Slow relaxing reflexes

Hoarse voice

Ataxia

Thin and brittle hair

Loss of lateral one third of eyebrow

Cold hands

Ileus (paralytic obstruction of bowels)

21
Q

How do you distinguish between primary and secondary diseases

A

Interpreting TFTs:

  • Check T4 first to determine if hyper or hypo
  • Then check TSH to see if 1o or 2o disease

Primary diseases originate in the thyroid gland
- TFTs will go in “opposite directions” i.e. Primary
hypothyroidism has reduced T4 and high TSH

Secondary diseases originate from higher up the
HPT axis
- TFTs will go in the “same direction” i.e. secondary
hypothyroidism has low TSH and subsequently low T4

All to do with negative feedback

22
Q

what is the management of hypothyroidism

A

Levothyroxine
- Doses are tapered up in patients with cardiac
issues/severe hypothyroidism
- Doses are dependent on patients body weight
- Measure cortisol level
- Treatment is life long
- start on a low dose and work up as it can cause angina and an MI

Treat underlying cause (e.g. surgery for pituitary
adenoma)

TFTs three months after administration
- Yearly follow ups after this

23
Q

what does a decrease in cortisol cause

A

Addison’s presents with similar symptoms

Addison’s is an autoimmune condition

Cortisol is important to test before administration to
avoid an addisonian crisis

24
Q

what does a decrease in B12 cause

A

Symptoms

Pernicious anaemia is autoimmune

Hypothyroidism can cause B12 deficiency

25
Q

hypothyroidism can cause a low….

A

B12 (B12 deficiency)

26
Q

describe the hypothalamic pituitary axis role in the regulation of the thyroid hormones

A

Answer: The hypothalamus secretes thyrotropin-releasing hormone
(TRH).

TRH stimulates the Anterior pituitary gland to release thyroid stimulating
hormone (TSH).

TSH stimulates triiodothyronine (T3) and thyroxin (T4) production from
the thyroid gland.

This process is homeostatically controlled by negative feedback, whereby
T3 & T4 supress both TRH and TSH.

27
Q

Describe the cellular processes that lead to the release of thyroid hormone

A

Thyroid hormones are produced in the follicular cells of the thyroid gland. Iodide I-
moves into the follicular cell from the blood through a Na+/I- symporters on the
basolateral membrane of the cell. This is a secondary active transporter that uses the
concentration gradient of sodium ions to move iodide against its concentration
gradient. This iodide then moves across the apical membrane and into the colloid.

Iodide is oxidised to iodine in the colloid by thyroid peroxidase.

At the same time, thyroglobulin is synthesised in the rough endoplasmic reticulum and
follows the secretory pathway to enter the colloid in the lumen of the thyroid follicle
by exocytosis. Iodine is very reactive and iodinates the tyrosyl residues of the
thyroglobulin (thyroid peroxidase). The tyrosyl residues pair together in conjugation

The iodinated thyroglobulin is then endocytosed back into the cell. On entering the cell
there is fusion with lysosomes where proteolysis occurs by various proteases, which
result in the release of thyroxine and triiodothyronine which are then exocytosed into
the blood.

28
Q

What is the main activating enzymes converting T4 into T3

A

deiodinase 2

29
Q

in a lady with primary hyperthyroidism what would you expect to see on her blood results

A

High free triiodothyronine (T3) & thyroxine (T4) and low

thyroid stimulating hormone (TSH) due to negative feedback

30
Q

A patient has moved to the UK from India recently. She complains of lethargy. Blood tests revealed Low T4 and High TSH. What is the most
likely diagnosis?

A

Primary Hypothyroidism

Iodine deficiency

31
Q

impact of thyroid hormone on cardiacmycoytes

A

x

32
Q

Thyroid and lipids

A
  • LPL helps deposit fat into adipose tissue
    T3 and T4 - regulate LPL so with increasing T4 and T3 decrease LPL can’t deposit fat into adipose tissue there there is hyperlipidemia in the blood
  • want it to be accessible to use
  • shows that LDL is high in the test results
33
Q

diagnosis

A

blood TSH
Blood T4
autoimmune anitbodies TPO, TG

34
Q

why is the HBaC1 high

A
  • increase gluconegoenss and increases glycongenolysis in the liver with breaks down glucose and releases it to the blood
  • therefore it rises and glcyoslaytes haemoglobin
35
Q

what is a goitre

A
  • abnormal enlargement of a thyroid gland
  • caused by hypertrophy of the gland
  • infiltration of immune cells that can remodel it and causes fibrosis deposits
  • most common cause is iodine deficiency
  • iodine is in fruit and veg, found in sea water and costal areas, therefore landlocked people more likely to be iodine deficient or high altitudes as you are less likely to get iodine
36
Q

who gets goitres

A
  • from in both hypothyroidism(such as hasmitos thyroditis - infiltration of immunocytes and destruction) and hyperthyroidism (such as graves - high TSH levels causes increased growth of hormones therefore increases size of thyroid)
  • more likely to get it in hyperthyroidism

Metabolism 2 PBL (9 decks)

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