Week 5.1

Question 1

Where is mineralocorticoid produced & secreted?

Answer 1

Zona glomerulosa (cortex of adrenal gland)

Question 2

Where is glucocorticoid produced…

Answer 2

Zona fasciculata (cortex)

Question 3

Where is adrenal androgen produced…

Answer 3

Zona reticularis (cortex)

Question 4

Where are catecholamines produced?

Answer 4

Medulla of Adrenal gland

Question 5

What is the main GC:

Answer 5

cortisol / and some corticosterone

Question 6

What is the main MC:

Answer 6

aldosterone

Question 7

Pathway of aldosterone signalling

Answer 7

Renin -> Angiotensin (I/II) -> Aldosterone

Question 8

The pathway of aldosterone synthesis (enzyme)

Answer 8

Cholesterol –> DOC –> Aldosterone
Enzyme: aldosterone synthase

Question 9

Cortisol + corticosterone synthesis

Answer 9

Cortisol comes from cholesterol too
enzyme: 11-betaOH (hydroxylase)
Corticosterone comes from DOC (precursor of aldosterone)

Question 10

is half life of aldosterone high or low?

Answer 10

low (minutes)

Question 11

affinity of MR and GR

Answer 11

MR is higher than GR

Question 12

is MR affected by cortisol?

Answer 12

yes

Question 13

How is the high cortisol regulated in signalling to receptors

Answer 13

11beta-HSD2 in tissues, it blocks cortisol, so only MC will signal to MR

Question 14

Drugs that inhibits mineralocorticoids action

Answer 14

Epi: no side effect
Spiro: side effect -> inhibits androgen receptors too

Question 15

Drug – MC agonists

Answer 15

Fludro: substitutes for aldosterone.
Treat addison’s disease, low aldosterone.

Question 16

aldosterone and Na+ reabsorption pathway

Answer 16

1. Apical surface: aldosterone – MR – will let nucleus stimulate more ENaC (sodium inlet)
2. Na+ is reabsorbed to circulation through Na/K pump, K+ comes in
3. K+ will be pumped out through ROMK

Question 17

Sodium reabsorption and aldosterone (side effects)

Answer 17

Hypertension:
Aldosterone will lead to reabsorption of sodium intra-cell becomes more negative.
Cl- is also pumped out -> increase in osmolarity due to ion accumulation.
releases ADH this will increase ECF and leads to hypertension.

Question 18

Excessive aldosterone biochemical effect

Answer 18

Increased Na+ and Cl- pumped out.
Increased H+ and K+ cellular uptake.

Question 19

Excessive aldosterone effect (symptom–)

Answer 19

1. Hypertension
   2.Hypokalaemia - muscle cramps
   3.alkalosis.

Question 20

Aldosterone deficiency leads to .. (biochem and symptom)

Answer 20

Due to decreased Na+ reabsorption and Cl- pumped into circulation:
1. Low BP
2. Decreased cellular uptake of K+ and H+.

Question 21

How does renal artery stenosis affect aldosterone level

Answer 21

1. High Renin and Aldosterone
2. Blocked artery to kidney
3. kidney senses low BP
4. thinks it is low blood volume
5. Kidney stimulates renin production -> aldosterone (secondary)

Question 22

Adrenal overfunction and aldosterone

Answer 22

Primary
1. Adrenal gland produces a lot of aldosterone
2. Renin is turned off
3. High aldosterone/Renin ratio

Question 23

Pseudo-hyperaldosteronism

Answer 23

It’s actually not high aldosterone
1. Genetic mutation that leads to increased BP and decreased circulating K+.
2. Low aldosterone and renin

Question 24

Adrenal insufficiency disease

Answer 24

Addison’s

Question 25

Adrenal insufficiency and aldosterone

Answer 25

The adrenal gland will lead to decreased aldosterone production. High renin (small -ve feedback)

Question 26

Pseudo-hypoaldosteronism

Answer 26

Apparent high K+ and low BP **Renin** and **aldosterone** high.

Question 27

Addison's Disease (hormone change)

Answer 27

**Adrenal disease**: Low MC - aldosterone and GC - cortisol 1. high Renin (low aldo) 2. high CRH and ACTH - hypothalamus & anterior pituitary.

Question 28

Pathway of GC (cortisol) signalling

Answer 28

Hypothalamus -> Anterior Pituitary -> Adrenal cortex

Question 29

Hypothalamus hormone to anterior pit.

Answer 29

CRH (corticotropin releasing hormone)

Question 30

Anterior pituitary hormones

Answer 30

ACTH to adrenal gland - Other hormones: LH, FSH, TSH, GH, prolactin, ADH.

Question 31

Hypothalamus dysfunction and cortisol pathway (causes - consequences)

Answer 31

**Destructive hypothalamic disease**: **CRH low** & downstream hormones low

Question 32

What could lead to anterior pituitary dysfunction

Answer 32

Large **non-functional** pituitary tumour: The adenoma will not produce active hormones itself.

Question 33

non-functional pituitary adenoma and cortisol pathway

Answer 33

**Low ACTH** & other pituitary released hormones -> low downstream hormones

Question 34

What is an apparent symptom of Addison's disease

Answer 34

Adrenal gland dysfunction: -> increased ACTH (along with CRH) ACTH will lead to hyper-pigmentation

Question 35

What will excessive ACTH cause???

Answer 35

melanocyte-stimulating hormone receptor (release melanin) hyper-pigmentation.

Question 36

Causes of Addison's disease

Answer 36

Autoimmune, Metastasis, tuberculosis. -> damage to the adrenal cortex

Question 37

low Cortisol effects

Answer 37

vascular tone- Low blood pressure Low glucose Loss of Appetite

Question 38

Pituitary ACTH deficiency

Answer 38

low cortisol and normal aldosterone (unaffected)

Question 39

Short Synacthen Test

Answer 39

Synacthen is an ACTH-like drug It **should stimulate adrenal cortex** to release **cortisol** If abnormal -> adrenal cortex atrophy (dysfunction) Inaccurate within 6 months of hypot/pit. damage. Adrenal gland needs 4-6 weeks to completely fail cortisol production.

Question 40

What is Cushing's syndrome

Answer 40

Excessive cortisol production

Question 41

Cushing's syndrome leads to --

Answer 41

Increased circulating glucose. Increased protein catabolism. - skin thinning - easy bruising High levels of cortisol: increased bone resorption and decreased bone formation: **Osteoporosis**

Question 42

Causes of Cushing's syndrome (3)

Answer 42

1. Pituitary tumour -> excessive ACTH 2. Ectopic ACTH. Leads to increased cortisol, more -ve feedback to hypothalamus and anterior pituitary. 3. Adrenal tumour -> increased cortisol.

Question 43

Diagnosis of cause of Cushing's syndrome

Answer 43

Urine ACTH test: 1. low ACTH -> adrenal tumour 2. high ACTH -> pituitary/ectopic ACTH tumour

Question 44

Ectopic ACTH vs Pituitary ACTH tumour

Answer 44

**Pituitary ACTH tumour** : Can be suppressed by Dexamethasone suppression and CRH. **Ectopic ACTH** is often more intense: -Can have wait loss (weight gain is often the case for Cushing's) -ACTH is usually unaffected by dexamethasone suppression and CRH test.

Question 45

CRH test

Answer 45

For pituitary ACTH tumour -> a dose of CRH can increase the ACTH. For Ectopic ACTH tumour-> CRH cannot affect the ectopic tumour.

Question 46

dexamethasone suppression

Answer 46

Dexamethasone -> synthetic glucocorticoid that aims to negative feedback to ACTH production. - **Can suppress** in pituitary ACTH tumours. - **Cannot** in ectopic ACTH tumours.

Question 47

Adrenal insufficiency symptoms

Answer 47

low cortisol--low **glucose** **low BP** - vascular collapse low aldosterone--**low Na+, high K+** **very fatigue weight loss**

Question 48

Conn's tumour and bilateral adrenal hyperplasia

Answer 48

Excessive aldosterone. Imaging might distinguish the two. Adrenal vein sampling where **Conn's tumour have more aldosterone** on one side.