The Adrenal Glands Flashcards
1
Q
What are the three gross layers of the adrenal glands?
A
Capsule, Cortex, Medulla
2
Q
Where are the adrenal glands found?
A
Above the kidneys
3
Q
What three layers can the cortex be broken down into?
A
Zona glomerulosa, Zona fasiculata, and Zona reticularis
4
Q
What is the adrenal medulla and what do they secrete?
A
Chromaffin cells which secrete 80% adrenaline and 20% noradrenaline
5
Q
What does the Zona Glomerulosa secrete?
A
Secretes mineralocortcoids (eg. alsosterone (salt))
6
Q
What does the Zona fasiculata secrete?
A
Secretes glucocorticoids (eg. cortisol (Sugar))
7
Q
What does the Zona reticularis secrete?
A
Secretes glucocorticoids and small amounts of androgens
8
Q
What kind of hormones are secreted from the adrenal cortex?
A
Steriod hormones derived from cholesterol
9
Q
Where are steroid hormones synthesised?
A
In adrenal glands and gonads
10
Q
How do steroid hormones exert change?
A
They are lipid soluble hormones that bind to intracellular receptors of the nuclear receptor family to modulate gene transcription
11
Q
What are examples of steroid hormones found in the adrenal cortex?
A
- Glucocorticoid
- Mineralocorticoid
- Androgens
- Oestrogen
- Progestins
12
Q
What stage of steroid hormone synthesis would be responsible for congenital adrenal hyperplasia?
A
21-hydroxylase enzyme deficiency
13
Q
How do corticosteroids regulate gene transcription?
A
- They readily diffuse across membranes and bind to glucocorticoid receptors in the cytoplasm.
- This causes dissociation of chaperone proteins
- Receptor-ligand complex translocates to nucleus where dimerisation can occur
- Receptors bind to glucocorticoid response elements (GREs) or other transcription factors
14
Q
What is aldesterone?
A
Most abundant form of mineralocorticoid
15
Q
Where is aldesterone made?
A
Synthesised and released by Zona glomerulosa of adrenal cortex
16
Q
How does aldesterone work and what does it affect.
A
- Binds to intracellular aldosterone receptors and exerts action by altering gene transcription
- Plays role in regulation of plasma Na+, K+ and arterial blood pressure.
- Central component of renin-angiotensin-aldosterone system (RAAS)
17
Q
How does aldosterone regulate plasma Na+/K+ concentration and blood pressure?
A
- Mainly works in distal tubules and collecting ducts of nephron
- Promotes expression of Na+/K+ ATPase pumps to promote reabsorption of Na+ and excretion of K+
- This increases water retention and therefore increases blood volume and pressure.
18
Q
What is the input of the RAAS?
A
- Hypotension
- Hypovolaemia
- This causes a decrease in renal perfusion, decrease in blood pressure ans increased sympathetic tone
- Baroreceptor activation leads to more renin being released from the kidney
19
Q
What effect does more renin release have on the RAAS?
A
Causes the cleaving of angiotensinogen (released by the liver) into Angiotensin I.
20
Q
What does Angiotensin Cleaving Enzyme (ACE) do in RAAS?
A
Cleaves Angiotensin I into Angiotensin II in lung epithelial cells
21
Q
What effect does Angiotensin II have on the body?
A
Causes:
- Vasoconstriction in arterioles
- Promotes synthesis of aldosterone on the adrenal cortex leading to the reabsorption of Na+ and water back into the blood
- Stimulates posterior pituitary to secrete ADH to aid further water reabsorption with aquaporins.
22
Q
What are the main outputs of the RAAS?
A
Increased blood volume and pressure.
23
Q
How could ACE inhibitors be used clinically?
A
ACE inhibitors limit the production of Angiotensin II which means it can be used as a antihypertensive drug
24
Q
What is Hyperaldosteronism?
A
Too much aldosterone produced
25
What is primary hyperaldosteronism
A defect in adrenal cortex
| - Low renin levels --> High aldosterone:renin ratio)
26
What is the most common form of hyperaldosteronism?
- Bilateral ideopathic adrenal hyperplasia (adrenal glands get bigger)
- Conn's Syndrome ( aldosterone secreting adrenal adenoma)
27
What is secondary Hyperaldosteronism?
Due to over activity of the RAAS
Caused by:
- Renin producing tumor eg. jaxtamedullary tumour
- Renal artery stenosis
- High renin levels --> low aldosterone:renin ratio
28
What is the best way to distinguish between primary and secondary Hyperaldosteronism
Best to distinguish between aldosterone:renin ratios
Primary: High aldosterone:Renin Ratio
Secondary: Low aldosterone:Renin Ratio
29
What are the signs of Hyperaldosteronism?
- High BP
- Left ventricular hypertrophy
- Stroke
- Hypernatraemia
- Hypokalaemia
30
What are the treatments of Hyperaldosteronism?
Depends on the type:
- Aldosterone-producing adenomas removed by surgery
- Spironolactone (mineraloscorticoid receptor antagonist)
31
What is cortisol
Most abundant corticosteroid and accounts for ~95% glucocorticoid activity
32
What is aldosterone's carrier protein?
Mostly serum albumin and to a lesser extent transcortin
33
What is cortisol's main carrier protein in plasma?
Transcortin
34
Where is cortisol synthesised and released?
In the Zona fasiculata in response to ACTH
35
What controls ACTH and CRH release?
Negative feedback mechanisms in the Hypothalamus-Pituitary Axis (in particular the hypothalamus)
36
What actions does cortisol have on the body?
- Increased proteolysis in muscle
- Increased lipolysis in fat
- Increased gluconeogenesis in liver
- Provides resistance to stress by increasing supply of glucose and raising blood pressure by making vessels more sensitive to vasoconstrictors
- Anti-inflammatory effects (by inhibiting macrophage activity and mast cell degranulation)
- Depression of immune system
37
How can cortisol be useful clinically?
- Anti-inflammatory effects are useful for medications for allergic reactions
- Depression of the immune system means that cortisol is often prescribed to organ transplant patients
38
What are the net effects of glucocorticoid steroids on metabolism?
- Increased glucose production
- Breakdown of protein
- Redistribution of fat
39
What effect does glucocorticoid actions have on metabolism in muscle?
- Increased protein degradation
- Decreased Protein synthesis
- Decreased glucose utilisation
- Decreased sensitivity to insulin
Cortisol inhibits insulin-induced GLUT4 translocation in muscle (prevents glucose uptake --> "glucose sparing effect")
40
What effect does glucocorticoid actions have on metabolism of fat?
- Decreased glucose utilisation
- Decreased sensitivity to insulin
- Increased lipolysis
41
What effect does glucocorticoid actions have on metabolism in the liver?
- Increased glycogen storage (as increased glucose= increased insulin= increased glycogenesis)
- Increaded gluconeogenesis by increased activity of enzymes
- Increased amounts of enzymes
42
What is Cushing's Syndrome?
Chronic excess exposure to cortisol
43
What are the signs and symptoms of Cushing's syndrome?
- Plethoric moon-shaped face
- "buffalo hump"
- Abdominal obesity
- Purple striae
- Acute weight gain
- Hyperglycaemia
- Hypertension
44
Where does the moon-face and buffalo hump come from?
Chronic high levels of cortisol results in redistribution of fat especially in abdomen, supraclavicular fat pads ("buffalo hump") and on the face ("moon face")
45
What is the most common cause of Cushing's syndrome?
External causes= Prescribed glucocorticoids
46
What are the endogenous causes of Cushing's syndrome?
- Cushing's Disease: Benign pituitary adenoma secreting ACTH
- Adrenal Cushing's: Excess cortisol produced by adrenal tumour
- Ectopic Tumours: Non-pituitary-adrenal tumours producing ACTH (&/or CRH) eg. small cell lung cancer
47
What are examples of steroid drugs and what are they used to treat?
eg. Prednisolone and Dexamethasone
Used to treat:
- Asthma
- Inflammatory bowel disease
- Rheumatoid arthritis
- Other auto-immune conditions
- Supress immune system after organ transplants
48
What effects do steroid drugs have?
Anti-inflammatory and immunomodulatory effects
49
What side effects do steroid drugs have?
The same effects as higher levels of cortisol, plus can have a mineralocorticoid effects
50
What is Addison's Disease?
Chronic Adrenal insufficiency
51
What is the most common cause of Addison's Disease?
Destructive atrophy from autoimmune response
52
What are the signs and symptoms of Addison's Disease?
- Postural hypotension
- Lethargy
- Weight Loss
- Anorexia
- Increased skin pigmentation
- Hypoglycaemia
53
Why does hyperpigmentation occur in Addison's?
Decreased cortisol --> Negative feedback on anterior pituitary reduced --> more POMC required to synthesise ACTH --> More ACTH and MSH
- Increased MSH as consequence of increased POMC leads to hyperpigmentation by stimulating melanocytes
- ACTH also activates melanocortin receptors on melanocytes so will contribute to hyperpigmentation
54
What is an Addisonian Crisis?
Life threatening emergency due to adrenal insufficiency
55
What leads to an Addisonian Crisis?
- Severe stress
- Salt deprivation
- Infection
- Trauma
- Cold exposure
- Over exertion
- Abrupt steroid drug withdrawal
56
What are symptoms of Addisonian Crisis?
- Nausea
- Vomiting
- Pyrexia
- Hypotension
- Vascular Collapse
57
What is the treatment for an Addisonian Crisis?
- Rapid fluid replacement
| - Intravenous Cortisol
58
Where are androgens synthesised?
Zona reticularis secretes weak androgens Dehydroepiandrosterone (DHEA) and androstenedione
59
What regulates androgen secretion?
Partially regulated by ACTH and CRH
60
What does DHEA do in males?
DHEA is converted to testosterone in testes.
Before puberty this the main source of testosterone, but after puberty the testes play a greater role so DHEA is irrelevant
61
What do androgens do in females?
Adrenal androgens promote libidoand are converted oestrogens by other tissues.
After menopause this is the only source of oestrogens
62
What do androgens do in both sexes?
Promote axillary and pubic hair growth
63
What is adrenal medulla?
Modified sympathetic ganglions of the autonomic nervous system
64
What do chromaffin cells in the medulla do?
They lack axons but act postganglionic nerve fibres that release hormones into the blood.
Releases 80% adrenaline and 20% noradrenaline
65
Why do chromaffin cells release a mixture of noradrenaline and adrenaline?
~20% of chromaffin cells lack N-methyl transferase enzyme that converts noradrenaline into adrenaline and so releases some noradrenaline
66
How does adrenaline and noradrenaline exert its actions?
By binding to GCPRs
67
What is a phaeochromocytoma?
Chromaffin cell tumour
- A rare, catecholamine-secreting tumour (mainly noradrenaline)
- May precipitate into life-threatening hypertension
68
What are the characteristics of phaeochromocytoma?
- Severe hypertension
- Headaches
- Palpitations
- Diaphoresis (excessive sweating)
- Anxiety
- Weight loss
- Elevated blood glucose
69
What are catecholamines derived from?
Tyrosine
