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Metabolism > Week 9 > Flashcards

Week 9 Flashcards

0
Q

What is secreted by the adrenal gland?

A

Cortex - Zona glomerulosa - mineralocorticoids - aldosterone
Zona fasciculata - glucocorticoids - cortisol, corticosterone
Zona reticularis - androgens - dehydroepiandrosterone and glucocorticoids
Medulla - adrenaline and noradrenaline

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1
Q

What hormones are produced by the pituitary?

A

Anterior pituitary - FSH, LH, TSH, ACTH, prolactin, GH

Posterior pituitary - oxytocin, ADH

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2
Q

Where is the pituitary gland located?

A

Suspended on a stalk from the hypothalamus, in a deep recess in the sphenoid bone (pituitary fossa)

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3
Q

What is the weight of the pituitary gland, which gender is it larger in?

A

0.5-0.9g

Larger in females (effect of oestrogen on lactotrophs)

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4
Q

What is the blood supply to the pituitary?

A

Portal vein linking capillary beds in hypothalamus and anterior pituitary
Arterial supply - inferior and superior hypophyseal arteries arising from internal carotid artery

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5
Q

How does the pituitary gland develop?

A

Anterior pituitary is an up growth of ectodermal cells from the buccal cavity
Posterior pituitary is a down growth of neural tissue from hypothalamus

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6
Q

What cell types are present in the anterior pituitary?

A 
Lactotrophs
Somatotrophs - largest number of cells
Thyrotrophs
Gonadotrophs 
Corticotrophs
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7
Q

Where are the adrenal glands found?

A

Capping the upper poles of the kidneys, lying against the diaphragm

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8
Q

How much do the adrenal glands weigh?

A

6-8g, less in women

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9
Q

What is cortisol?

A

C21 steroid hormone synthesised from cholesterol via progesterone lipophilic

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10
Q

What is CRF?

A

Corticotrophin releasing factor
Polypeptide (41aa) hormone released from hypothalamus
Stimulates release of ACTH from corticotrophs in anterior pituitary

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11
Q

What controls the rate of secretion of CRH?

A

Negative feedback from cortisol
Physical stress - temperature and pain
Emotional stress
Chemical stress - hypoglycaemia

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12
Q

What’s ACTH?

A

39 amino acid polypeptide hormone produced from proteolytic cleavage of POMC
Contains the 13 at sequence of alpha MSH, therefore has similar properties when present in excess.

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13
Q

What is the half life of ACTH in the circulation?

A

Eight minutes

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14
Q

How does the concentration of ACTH vary?

A

Circadian rhythm - higher in the morning, lower at night

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15
Q

How does ACTH act on cells in the adrenal cortex?

A

Acts on high affinity receptors (melanocortin receptors type 2) on cells in Zona fasciculata and Zona reticularis. Uses cAMP as a second messenger. Activates cholesterol esterase to produce free cholesterol, stimulates other steps in the synthesis of cortisol

16
Q

How is cortisol carried in the plasma?

A

90% bound to corticosteroid-binding globulin (CBG) also known as transcortin
10% free and active

17
Q

How does cortisol act on cells?

A

Crosses plasma membranes and binds receptors in the cytosol ask
Hormone receptor complex enters nucleus and binds specific areas of DNA
Changes the rate of transcription of certain genes

18
Q

What are the actions of cortisol on target cells?

A

Decrease amino acid uptake and protein synthesis, and increase proteolysis in most tissues - not liver
Increase lipolysis (excess cortisol increases lipogenesis in adipose tissue)
Increase hepatic gluconeogenesis and glycogenolysis
Decrease glucose uptake in peripheral tissues.
Indirect effects on cardiac muscle, bone and the immune system

19
Q

What is the adrenal medulla?

A

Modified sympathetic ganglion, synthesises catecholamines such as adrenaline, and neurotransmitters like dopamine and noradrenaline.

20
Q

How are catecholamines stored?

A

In membrane limited vesicles in medullary cells

21
Q

HOw are catecholamines synthesised?

A

Tyrosine -> dopamine -> noradrenaline -> adrenaline

22
Q

What are the actions of adrenaline?

A

Increases cardiac output and blood supply to skeletal muscle
Increases mental alertness
Increases lipolysis in adipose tissue
Increases glycogenolysis in liver and skeletal muscle

23
Q

What is phaeochromocytoma?

A

Over secretion of adrenaline by adrenal medulla due to a tumour
Causes hypertension, sweating, palpitations, glucose intolerance, pallor and anxiety

24
Q

What is congenital adrenal hyperplasia?

A

Deficiency in one of the enzymes required for the synthesis of cortisol.
Lack of feedback inhibition of ACTH leads to increased secretion of ACTH, causes enlargement of the adrenal cortex - hyperplasia

25
Q

What might cause Cushing’s syndrome?

A

Increased secretion of cortisol due to:
Adenoma in the adrenal gland
Pituitary adenoma (Cushing’s disease), increased ACTH secretion
Ectopic secretion of ACTH

26
Q

What causes Addison’s disease?

A

Autoimmune destruction of adrenal cortex - affects glucocorticoids and mineralocorticoids
Disorders in pituitary or hypothalamus, leading to decreased secretion of CRH or ACTH - only affects glucocorticoids.

27
Q

What are the signs and symptoms of excess cortisol secretion?

A

Steroid diabetes - hyperglycaemia due to hepatic gluconeogenesis and proteolysis of muscle
Increased lipogenesis - weight gain, central obesity and deposition of fat around the face and neck - characteristic buffalo hump, moon face.
Muscle proteolysis-weakness, thin arms and legs
Purple striae on lower abdomen, upper arms and thighs due to proteolysis of structures in the skin, easy bruising due to thinning of skin and subcutaneous tissue
Immunosuppressive, antiallergic and anti-inflammatory - increased susceptibility to bacterial infections and producing acne
Disturbed calcium metabolism and loss of bone matrix protein - back pain and collapse of ribs
Hypertension due to sodium and fluid retention- mineralocorticoid effects of cortisol

28
Q

What are the clinical signs and symptoms of decreased cortisol secretion?
What about decreased mineralocorticoid secretion in autoimmune destruction of the adrenal cortex?

A

Tiredness, muscle weakness, anorexia, abdominal pain, occasional dizziness, weight loss, dehydration,
Increased pigmentation, especially in exposed areas of the body, buccal mucosa, scars, palmar creases and areas of friction duets stimulation of melanocytes by ACTH
Hypotension due to loss of mineralocorticoids, and postural hypotension
Fasting hypoglycaemia

29
Q

What causes Addisonian crisis?

A

Trauma or severe infection.

30
Q

What are the symptoms of Addisonian crisis?

A

Nausea, vomiting, extreme dehydration, hypotension, confusion, fever, coma

31
Q

How do you treat Addisonian crisis?

A

Intravenous cortisol and fluid replacement (dextrose in normal saline)

32
Q

How do you test for Cushings disease?

A

Measure midnight cortisol (when it should be low)
Dexamethasone suppression test - negative feedback of ACTH,
Low does suppresses cortisol in healthy people, if not suppressed, Cushing’s syndrome
High dose suppresses if cortisol is suppressed by >50%,cushings disease.
Can’t suppress ACTH secretion from ectopic tumours

33
Q

How do you test for Addison’s disease?

A

9am cortisol
Synacthen test - stimulates adrenal glands to produce cortisol. If adrenal failure, no response.
If pituitary is not producing ACTH, produce cortisol in response to synacthen.

34
Q

What is the structure of a steroid hormone receptor?

A

Three regions:
DNA binding region, rich in cysteine residues and basic amino acid residues
Variable region
Hydrophobic hormone binding region

35
Q

What is steroid hormone receptor homology?

A

The amino acid sequence in the hormone binding regions of steroid hormone receptor molecules have similarities.
The glucocorticoid receptor has 64% homology with mineralocorticoid receptors, 62% homology with androgen receptors, 31% with oestrogen receptors and 24% with thyroid receptors.
When high levels of cortisol present, binds androgen and mineralocorticoid receptors with low affinity - explains some symptoms.

36
Q

What does aldosterone do?

A

Stimulates reabsorption of sodium ions in exchange for potassium ions, causes water retention, increases blood pressure

37
Q

What do androgens do?

A

Promote development of male secondary sexual characteristics- height, body shape, hair, voice
Anabolic actions especially muscle protein
In women, hirsutism, acne, menstrual problems, increased muscle bulk, deepening voice, virilisation

38
Q

What is the role of oestrogens?

A

Growth and development of female genital tract and secondary sexual characteristics- breasts, pubic hair, broad hips, buttocks,
Weakly anabolic, decrease circulating cholesterol levels

Metabolism (9 decks)

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