Endocrinology 2 Flashcards

The Adrenals, Gonads and Parathyroids

1
Q

Describe the vasculature of the adrenal glands.

A

Both adrenal glands have many arteries but only one vein each.
The right adrenal vein drains into the inferior vena cava.
The left adrenal vein drains into the renal vein.

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2
Q

Give the basic anatomy of an adrenal gland.

A
From medial to lateral:
Adrenal medulla
Zona reticularis
Zona fasciculata                  
Zona glomerulosa 
Capsule
((the zona reticularis, zona fasciculata and zona glomerulosa comprise the adrenal cortex)).
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3
Q

Which hormones are produced by chromaffin cells in the adrenal medulla?

A

Adrenalin (80%)
Noradrenaline (20%)
Dopamine

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4
Q

Which hormones are produced in the zona glomerulosa?

A

Mineralocorticoids, mainly aldosterone.

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5
Q

Which hormones are produced in the zona fasciculata and zona reticularis?

A

Glucocorticoids, mainly cortisol.

Small amounts of androgens and oestrogens.

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6
Q

What is the difference in circulating levels of aldosterone and cortisol?

A

Cortisol circulates at around 1000 times higher concentrations than aldosterone.

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7
Q

Which receptors do aldosterone and cortisol bind to?

A

Cortisol binds to the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR), whereas aldosterone only binds to MR.

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8
Q

How do certain tissues prevent cortisol from entering, and thus rely on aldosterone for MR binding?

A

They have high levels of an enzyme - 11b-hydroxysteroid dehydrogenase 2 (11b-hsd 2).
The placenta and kidneys have a lot of this enzyme.
This converts cortisol to cortisone, an inactive hormone.

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9
Q

Describe the renin-angiotensin-aldosterone system.

A

Renin is released from granular cells in the kidneys in response to:
Decreased renal perfusion pressure (RPP).
Renal sympathetic activity.
Decreased Na+ load at macular densa cells in the DCT

Renin is an enzyme, which converts angiotensinogen from the liver) into angiotensin I. ACE (angiotensin converting enzyme) in the lungs converts angiotensin I to angiotensin II.

Angiotensin II causes aldosterone to be released from the zona glomerulosa of the adrenal cortex.

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10
Q

Other than angiotensin II, what other two stimuli cause aldosterone to be released from the zona glomerulosa?

A

Low blood sodium ion concentration; high blood potassium ion concentration.

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11
Q

Which two hormones are involved in the control of the rate of cortisol release?

A

A hypothalamic hormone, corticotrophin releasing hormone, and an adenohypophyseal hormone released from Corticotrophs: ACTH (Adrenocorticotrophic hormone).

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12
Q

What are the physiological effects of aldosterone?

A

Aldosterone acts on distal tubule cells. It increases the numbers of sodium ion channels on the apical membrane and sodium/potassium ATPases on the basal membrane by acting on the nucleus to increase transcription and translation. Result is increased sodium ion reabsorption.

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13
Q

What are the physiological effects of cortisol?

A

Increases gluconeogenesis and glycogenolysis by promoting enzymes involved in both of these processes.
Stops glucose being stored peripherally by decreasing blood flow to adipose tissue and skeletal muscle and decreasing numbers of lipoprotein lipase and GLUT 4 respectively. Also prevents free fatty acids being stored: the result is that energy substrates remain in the blood, available for use.
It is also pro-memory by upregulating serotonin.

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14
Q

Give the supra-physiological effects of cortisol.

A

Anti-inflammatory/immunosuppressive.

Excess GR activation - negative effect on serotonin, becoming anti-memory (hippocampus may get smaller).

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15
Q

How is calcium found in the body?

A

99% is found in the bone as complex hydrated calcium.
In the blood:
50% is found as bioactive ionised calcium (Ca2+)
45% is bound to plasma proteins.
5% is found as diffusible salts (citrate, lactate).

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16
Q

Which hormones have effects on levels of calcium in the blood?

A

Plasma calcium ions INCREASED by calcitriol (1,25 (OH)2 Vitamin D3) and parathyroid hormone (PTH).
Levels DECREASED by calcitonin.

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17
Q

Which cells release calcitonin?

A

Parafollicular cells of thyroid.

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18
Q

How is PTH synthesised and how does it signal to cells?

A

Initially synthesised as pre-pro PTH. Binds to transmembrane G-protein linked receptors. Activates adenyl cyclase and also probably phospholipase C (PLC).

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19
Q

What are the effects of PTH?

A

On BONE osteoclasts are stimulated and osteoblasts inhibited, resulting in bone resorption.
On KIDNEYS: increased Ca2+ reabsorption and increased phosphate excretion. Stimulates 1-a hydroxylase activity which results in increased calcitriol synthesis.
Calcitriol acts on SMALL INTESTINE to increase absorption of both Ca2+ and phosphates.

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20
Q

How does PTH result in bone resorption?

A

It binds to the PTH receptor on OSTEOBLASTS which produce osteoclast activating factors (OAFs). These act on osteoclasts to result in bone resorption.

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21
Q

What promotes and inhibits PTH release from parathyroid glands?

A

Decreased plasma Ca2+ result in PTH secretion. Catecholamines (adrenaline, dopamine) promote PTH secretion.
Calcitriol inhibits PTH release, as does raised blood plasma concentrations of Ca2+.

22
Q

How is calcitriol synthesised?

A

In the skin, UV light initiates the conversion of 7-dehydrocholesterol into cholecalciferol. Some cholecalciferol is also ingested in the diet. Cholecalciferol is vitamin D3.
Vitamin D3 is converted to 25-hydroxy-cholecalciferol in the liver.
1-a hydroxylase (stimulated by PTH) converts 25-hydroxy-cholecalciferol into 1,25 dihydroxy-cholecalciferol in the kidneys. This is calcitriol.

23
Q

What are the actions of calcitriol (1,25 (OH)2 D3)?

A

In BONE: increased osteoblast activity.
In SMALL INTESTINE: increased Ca2+ and phosphate absorption.
In KIDENYS, increase in Ca2+ reabsorption.

24
Q

How do fibroblast factor 23 (FGF-23) and PTH cause phosphate excretion?

A

They inhibit the Na+/phosphate cotransporters on the apical membrane of collecting duct cells.

25
Q

What causes calcitonin release from parafollicular cells?

A

Gastrin (from the stomach) and increased plasma Ca2+ levels.

26
Q

How does calcitonin decrease plasma Ca2+ levels?

A

Causes the kidneys to increase urinary excretion of Ca2+.

Causes inhibition of bone osteoclasts.

27
Q

Give 3 causes of hypocalcaemia.

A

Hypoparathyroidism.
Pseudohypoparathyroidism (defective G-protein causes target organ resistance to PTH).
Vitamin D deficiency.

28
Q

Give 3 causes of hypercalcaemia.

A

Primary and tertiary hyperparathyroidism.

Vitamin D toxicosis.

29
Q

What is POMC?

A

Pro-opiomelanocortin.

It is a precursor for ACTH and MSH (melanocyte-stimulating hormone).

30
Q

What is Addison’s disease and its associated features?

A

Hypoadrenalism.
Dizzy when standing (postural hypotension - secondary to aldosterone deficiency).
Fatigue
Increased pigmentation. In adrenal failure, ACTH very high, so MSH high. Vitiligo may be present.

31
Q

What is Cushing’s syndrome and its associated features?

A
Levels of cortisol are too high. 
Proximal myopathy. 
Multiple purple striae (purple stretch marks).
Many bruises
Buffalo hump
Central obesity.
32
Q

What are the 2 main functions of the gonads?

A

Production of gametes (gametogenesis) and production of steroid hormones (steroidogenesis).

33
Q

Describe spermatogenesis.

A

Germ cell (44+XY)
Spermatogonia (44+XY) Mitosis
Primary spermatocytes (44+XY) 1st Meiotic Division
Secondary spermatocytes (22X or 22Y) 2nd Meiotic Division
Spermatids (22X or 22Y)
Spermatozoa (22X or 22Y).

34
Q

Describe oogenesis.

A

Germ cell (44XX)
Oogonia (44XX) Mitosis
Primary oocytes (44XX) 1st Meiotic Division
Secondary oocytes (22X) 2nd Meiotic Division
Ovum (22X)

35
Q

Where does spermatogenesis happen?

A

Spermatogonia migrate from blood through tight junctions between Sertoli cells, undergoing meiosis to become primary and secondary spermatocytes. Once they reach the lumen of the seminiferous tubules, they mature into spermatozoa.

36
Q

What do Sertoli cells do?

A

They form the seminiferous tubules and are intimately associated with developing spermatocytes. Synthesise FSH and androgen receptors. In response to FSH, produce various molecules including INHIBIN.

37
Q

What do Leydig cells do?

A

They lie outside seminiferous tubules. They synthesise LH receptors. In response to LH are the principle source of testicular androgens.

38
Q

How are the ovarian and endometrial cycles linked?

A

The follicular phase of the ovarian cycle causes oestrogen (17b-oestradiol) to be produced, inducing the proliferative phase of the endometrial cycle.
The luteal phase of the ovarian cycle causes progesterone to be released, inducing the secretory phase of the endometrial cycle.

39
Q

How is testosterone and dihydrotestosterone (DHT - the potent version of testosterone) bound in the blood and seminiferous fluid?

A

In the blood, 60% is bound to sex hormone binding globulin (SHBG), 38% to albumin, and 2% is the free bioactive version.
In seminiferous fluid, they are bound to androgen binding globulin (ABG).

40
Q

What is the definition of an oestrogen?

A

Any substance which induces mitosis in the endometrium.
17b-oestradiol (main one in women).
Oestrone (precursor).
Oestriol (main oestrogen produced in pregnancy).

41
Q

What does oestrogen do?

A

Stimulates proliferation of endometrium and triggers LH surge resulting in ovulation.

42
Q

What is the definition of a progesterone?

A

Any substance inducing secretory changes in the endometrium.
E.g. progesterone, 17a-hydroxyprogesterone.

43
Q

Describe the hypothalamo-pituitary testicular axis.

A

GnRH released from the hypothalamus causes LH, FSH to be released from adenohypophysis. LH causes Leydig cells to produce testosterone. FSH binds to Sertoli cells to produce inhibin and spermatogenesis. Testosterone and inhibin are involved in the negative feedback of adenohypophyseal and hypothalamic hormones.

44
Q

Describe the hypothalamo-pituitary ovarian axis.

A

GnRH released from the hypothalamus causes LH, FSH to be released from adenohypophysis. These act on the ovary to cause inhibin and oestradiol and progesterone to be released: these 3 are involved in the negative feedback mechanisms of the adenohypophyseal and hypothalamic hormones.

45
Q

What is amenorrhoea?

A

Absence of menstrual cycles.
Primary: woman has never had a single period.
Secondary: woman has had periods which then stop.

46
Q

What is oligomenorrhoea?

A

Infrequent cycles. Less severe than amenorrhoea.

47
Q

What is the WHO definition of infertility?

A

Couple can’t get pregnant following 12 months of regular unprotected sex.

48
Q

What happens in the early mid-follicular phase of the menstrual cycle?

A

Increases in 17b-oestradiol due to follicle growth.
Local (autocrine) positive feedback loop setup:
More granulosa cells = more oestrogen.

49
Q

What happens in the mid-follicular phase of the menstrual cycle?

A

Decrease in levels of FSH due to negative feedback by oestrogen and inhibin.
All follicles regress except the Graafian follicle.
No longer need FSH to develop and proliferate.

50
Q

What happens in the late follicular phase of the menstrual cycle?

A

Extremely high oestradiol levels from Graafian follicles causes positive feedback on GnRH/LH secretion i.e. LH surge / ovulation.

51
Q

What happens in the Luteal phase of the menstrual cycle?

A

Progesterone prepares the endometrium for implantation. No fertilisation: progesterone, oestradiol and inhibin exert a negative feedback on LH/FSH –> luteolysis and menstruation.