4.4 - The Adrenal Gland Flashcards
1
Q
Where are the adrenal glands?
A
- above the kidneys
- right and left adrenal glands
2
Q
How many arteries and veins does each adrenal gland have?
A
- both adrenals have many arteries but only one vein each
- right and left adrenal veins
- e.g. abdominal aorta, adrenal arteries, middle adrenal arteries, inferior adrenal arteries
3
Q
Where do the left and right adrenal veins drain into?
A
- left adrenal vein drains into renal vein
- right adrenal vein drains into IVC (inferior vena cava)
4
Q
What is the microanatomy of the adrenal glands?
A
- outer layer - zona glomerulosa
- middle layer (thickest) - zona fasciculata
- inner layer - zona reticularis
- zona glomerulosa, fasciculata and reticularis together form the adrenal cortex
- the adrenal medulla is found at the centre (inner to zona reticularis)
- capsule –> zona glomerulosa –> zona fasciculata –> zona reticularis –> medulla
5
Q
What hormones does the adrenal cortex produce and which zonas produce what?
A
Corticosteroids:
- mineralocorticoids - key one is aldosterone –> produced by zona glomerulosa
- glucocorticoids - cortisol –> produced by zona fasciculata and reticularis
- small amount of sex steroids - androgens and oestrogens –> produced by zona fasciculata and reticularis
6
Q
What are the steroid hormones synthesised from?
A
- all steroids synthesised from cholesterol
- it has 27 carbons
7
Q
What are the key steps of synthesis for aldosterone?
A
- cholesterol side chain cleavage forms pregnenolone
- 3-beta-hydroxysteroid dehydrogenase oxidises 3rd carbon in pregnenolone to form progesterone
- 21 hydroxylase adds OH group to carbon 21 of progesterone to form 11-deoxycorticosterone
- 11 hydroxylase adds OH group to carbon 11 to form corticosterone
- 18 hydroxylase adds OH group to carbon 18 to form aldosterone
8
Q
What are the key steps of synthesis for cortisol?
A
- cholesterol side chain cleavage forms pregnenolone
- 3-beta-hydroxysteroid dehydrogenase oxidises 3rd carbon in pregnenolone to form progesterone
- 17 hydroxylase adds OH group to carbon 17 of progesterone to form 7-hydroxyprogesterone
- 21 hydroxylase adds OH group to carbon 21 to form 11-deoxycortisol
- 11 hydroxylase adds OH group to carbon 11 to form cortisol
9
Q
What hormones does the adrenal medulla produce?
A
- neuroendocrine/chromaffin cells of the medulla produce catecholamines:
- adrenaline aka epinephrine (80%)
- noradrenaline aka norepinephrine (20%)
- dopamine
10
Q
How does aldosterone work?
A
- major net effect is to conserve body sodium by stimulating its reabsorption, and controlling BP
- binds to receptors in kidney and stimulates Na+ reabsorption in distal convoluted tubule and cortical collecting duct (and in sweat glands, gastric glands, colon)
- also stimulates K+ and H+ secretion in distal convoluted tubule and cortical collecting duct
- aldosterone switches on sodium-potassium ATPase which helps you reabsorb sodium and lose potassium (which goes into the urine)
- increased sodium reabsorption causes water absorption too, which increases blood volume and therefore increases blood pressure
11
Q
How is aldosterone regulated?
A
- in kidney, the juxtaglomerular apparatus (JGA) is always monitoring blood pressure
- decreased renal perfusion pressure (normally associated with decreased arterial BP), decreased Na+ load to top of loop of Henle (macula densa cells), and increased renal sympathetic activity (direct to JGA cells) = JGA release renin into blood
- the liver makes angiotensinogen protein which renin converts into angiotensin I
- angiotensin converting enzyme (ACE) in lungs converts angiotensin I –> angiotensin II, which works on zona glomerulosa to produce aldosterone (and other effects e.g. vasoconstriction)
- at zona glomerulosa, angiotensin II activates side chain cleavage, 3-hydroxysteroid dehydrogenase, 21, 11, 18 hydroxylases = more aldosterone produced
12
Q
What are the physiological effects of cortisol?
A
- normal stress response
- weak mineralocorticoid effects
- metabolic effects:
- peripheral protein catabolism
- hepatic gluconeogenesis
- increased BGC
- fat metabolism (lipolysis in adipose tissue)
- enhanced effects of glucagon and catecholamines
- renal and cardiovascular effects - excretion of water load, increased vascular permeability
13
Q
How is cortisol secretion regulated?
A
- cortisol, ACTH (adrenocorticotrophic hormone) and CRH (corticotrophin releasing hormone) have a negative feedback system
- increased cortisol means less CRH and ACTH secreted from hypothalamus and pituitary gland, and vice versa
14
Q
What is the effect of ACTH on the adrenals?
A
Activation of:
- side chain cleavage enzyme
- 3-hydroxysteroid dehydrogenase
- 17, 21, 11 hydroxylase
- results in cortisol production
15
Q
What kind of rhythm does cortisol have?
A
- diurnal rhythm
- increase starts at 12:30am and peaks at 8:30am, then decreases pretty much evenly to 12:30am again
- daily cycles - increase in ACTH = increase in cortisol - graphs mirror each other
16
Q
Where is the adrenal medulla derived from?
A
Ectodermal neural crest
17
Q
What are the steps for forming adrenaline and noradrenaline?
A
- tyrosine (precursor for Adr&NA synthesis) has O2 added to make dopa
- dopa has CO2 removed to form dopamine
- dopamine then converted to noradrenaline
- methyl donor group added to noradrenaline to form adrenaline
18
Q
Where are catecholamines stored and how are they released?
A
- stored in cytoplasmic granules
- released in response to ACh from preganglionic sympathetic neurones
19
Q
What is the role of catecholamines?
A
- fight or flight response e.g. tachycardia, sweating, increased BGC, alertness, vasoconstriction
- noradrenaline and adrenaline bound to albumin
- degraded by two hepatic enzymes: monoamine oxidase and catechol-O-methyl transferase
20
Q
What happens in Addison’s disease?
A
- primary adrenal failure
- autoimmune disease where the immune system decides to destroy the adrenal cortex –> cortisol and aldosterone deficiency
- salt loss
- TB of the adrenal glands is commonest cause worldwide
- pituitary starts secreting lots of ACTH and hence MSH (melanocyte-stimulating hormone)
- eventual death due to low BP
21
Q
What are the signs and symptoms of Addison’s disease?
A
- increased pigmentation of skin / hyperpigmentation
- autoimmune vitiligo may coexist (white patches in skin)
- no cortisol or aldosterone = low blood pressure
- adrenal crisis - syncope, fever, convulsions, hypoglycaemia, hyponatremia, severe vomiting and diarrhoea
- GI - nausea, vomiting, constipation, abdominal pain
- weakness
- weight loss
22
Q
Why do patients with Addison’s disease have a good tan (hyperpigmentation)?
A
- POMC (pro-opio-melanocortin) is a large precursor protein that is cleaved to form a number of smaller peptides, including ACTH, MSH and endorphins
- people who have pathologically high levels of ACTH will also have levels of MSH and may become tanned
23
Q
How do you treat Addison’s disease?
A
- rehydrate with normal saline
- give dextrose to prevent hypoglycaemia which could be due to glucocorticoid deficiency
- give hydrocortisone / another glucocorticoid
24
Q
What happens in Cushing’s syndrome?
A
- occurs due to an excess of cortisol or other glucocorticoid
- too much cortisol = metabolism changes and weight gain happens
25
Q
What are four possible causes of Cushing’s syndrome?
A
- taking steroids by mouth (common)
- pituitary dependent Cushing’s disease (pituitary adenoma)
- ectopic ACTH (lung cancer)
- adrenal adenoma / carcinoma
26
Q
What are the clinical signs and symptoms of Cushing’s syndrome?
A
- thin skin
- proximal myopathy - weakness of upper limbs
- centripetal obesity (lemon on sticks)
- diabetes, hypertension and osteoporosis
- immunosuppression (reactivation of TB)
- moon face
- striae (stretch marks)
- fat pads on back of neck
- poor wound healing and easy bruising
