MEH session 9 Flashcards
Which of the following is a characteristic of mineralocorticoid excess? Low serum sodium Low serum potassium Dehydration Hypotension
Low serum potassium
In which organ does cleavage of angiotensin I into angiotensin II mainly occur?
Lungs
Angiotensin I is converted to angiotensin II by the removal of two C-terminal amino acid residues by ACE within lung capillaries.
Which organ synthesises and releases angiotensinogen into blood?
Liver produces angiotensinogen
Angiotensinogen is cleaved by renin in plasma to form angiotensin I
Angiotensin I is cleaved by angiotensin converting enzyme (ACE) in lung capillaries to form angiotensin II
Would you expect the aldosterone:renin ratio to be high or low in a patient with secondary hyperaldosteronism caused by renal artery stenosis?
Low - there is a high concentration of renin
Renin released by juxtaglomerular cells of kidneys in response to low perfusion.
What is the mode of action of the drug spironolactone?
Mineralocorticoid receptor antagonist
Which disease is caused by aldosterone secreting adrenal adenoma?
Conn’s disease
Cortisol causes increased lipolysis in adipose tissue.
True or false?
True.
Although unusual fat deposition such as in the abdomen (central obesity), supraclavicular fat pads, dorsal-cervical fat pad (buffalo hump) and face (moon face) are signs of chronic exposure to high cortisol (Cushing’s syndrome), these are due to redistribution of fat
Primary action of cortisol in adipose is to increase lipolysis.
Which protein facilitates the transport of cortisol in the blood?
Transcortin - approx 75%
Albumin - rest
Explain why purple striae are often seen in Cushing’s syndrome.
Increased proteolysis due to high cortisol
Stretching of skin due to redistribution of fat
Which of the following is a sign of Addison's disease: Hyperglycaemia Skin hyperpigmentation Hypertension Buffalo hump fat deposition
Skin hyperpigmentation
Addison’s will result in a high ACTH due to removal of negative feedback of cortisol on the HPA. To make more ACTH, more POMC is produced and as a consequence of this more MSH is produced. Increased MSH will result in more melanin synthesis by activation of melanocortin receptors on melanocytes leading to hyperpigmentation. ACTH itself can also activate melanocortin receptors so will contribute
In which region of the adrenal gland is dehydroepiandrosterone (DHEA) mostly produced?
Zona reticularis layer of adrenal cortex - sex steroid production
Which type of enzyme catalyses the conversion of noradrenaline to adrenaline?
Methyl transferase - adrenaline is produced by methylation of nor-adrenaline
Which change in second messenger concentration would occur from the activation of the alpha 1 adrenergic receptor?
An increase in the concentration of IP3
Activation of which adrenergic receptor subtype mediates the effects of adrenaline and noradrenaline on the heart?
Beta 1
Increase chronotropy and inotropy
Activation of which adrenergic receptor subtype mediates bronchodilation in the lungs?
B2
A tumour of which cell type is called a pheochromocytoma?
Chromaffin cells of adrenal medulla
This tumour secretes catecholamines (mostly noradrenaline) resulting in symptoms such as severe hypertension, headaches, palpitations, excessive sweating, anxiety and weight loss.
How would plasma glucose concentration change with excess secretion of the hormone cortisol?
High plasma glucose
Cortisol increases plasma glucose by stimulating gluconeogenesis in the liver and inhibiting glucose uptake in muscle.
The plasma concentration of which hormone would increase as a consequence of Addison’s disease?
ACTH - due to a lack of negative feedback from cortisol
Why does hyperpigmentation sometimes occur in patients with Addison’s disease?
Decreased cortisol leads to increased expression of POMC
Removal of the negative feedback from cortisol on the hypothalamus leads to increased ACTH production. Melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) share the same precursor molecule, pro-opiomelanocortin (POMC) so increased POMC leads to an increase in both ACTH and MSH. Increased MSH results in darkening (hyperpigmentation) of the skin, including areas not exposed to the sun. Characteristic sites of darkening in Addison’s are skin creases (e.g. of the hands), nipple, and the inside of the cheek (buccal mucosa) also, old scars may often darken.
A patient has Cushing’s syndrome caused by excess cortisol production from an adrenal tumour. What effect would this condition have on plasma ACTH level?
ACTH would decrease
Excess cortisol from the adrenal tumour would inhibit ACTH secretion by negative feedback.
Which time of the day would be best to take a blood sample for cortisol measurement if Cushing’s syndrome is suspected?
Midnight
Blood cortisol levels are normally at their lowest level around midnight so high cortisol in a blood sample taken at midnight would be more indicative of Cushing’s than a high value taken in the morning when cortisol is normally at its highest level.
Which exogenous steroid is typically administered to patients as part of a suppression test to diagnose Cushing’s syndrome?
Dexamethasone suppression test (DST)
Used to assess adrenal gland function by measuring how cortisol levels change in response to an injection of dexamethasone. A normal result is a decrease in cortisol levels upon administration of low-dose dexamethasone. In Cushing’s syndrome, cortisol would not be suppressed by a low dose of dexamethasone.
Name the synthetic analogue of ACTH used in an ACTH stimulation test.
Syncathen
Administered intramuscularly
Would normally increase plasma cortisol by >200nmol/L. A normal response usually excludes Addison’s disease.
Is hypopituitarism resulting in ACTH deficiency classed as primary or secondary adrenal failure?
Secondary adrenal failure
Which of the following would you expect to see in a patient with Addison’s disease?
Recent weight gain
Fatigue
Hypertension
Skin depigmentation
Fatigue
Name a potential iatrogenic cause of Addison’s disease.
Adrenalectomy
Where are the adrenal glands located?
- Pair of multifunctional endocrine glands
- Cap the upper poles of the kidneys (lie in the same fascia)
- Lie against the diaghragm in the retroperitoneal space
Describe the structure of the adrenal gland.
- Small in size
- Outer cortex
- Inner medulla
Which types of hormones are released by the adrenal gland medulla?
Catecholamines - adrenaline and noradrenaline
Describe the embryonic development of the adrenal gland.
Cortex is derived from mesoderm
Medulla is derived from neural crest cells which subsequently migrate into the developing cortex
Where are catecholamines stored and by which cells in the adrenal gland?
Adrenaline is stored in membrane-bound vesicles in chromaffin cells of the medulla
Which types of hormones are released by the adrenal cortex?
Corticosteroid hormones -
Mineralocorticoids eg. Aldosterone
Glucocorticoids eg. Cortisol
Androgens eg. Dehydroepiandrosterone
What is the difference between the mode of action between corticosteroids and catecholamines?
Solubility:
Corticosteroids - lipid soluble
Catecholamines - water soluble
Receptors:
Corticosteroids - nuclear receptors
Catecholamines - GPCRs
Effect on enzymes:
Corticosteroids - regulates amount by gene expression
Catecholamines - regulates activity of existing enzymes
Speed of response:
Corticosteroids - slow (minutes to hours)
Catecholamines - fast (seconds)
What is the difference between the synthesis and release of corticosteroids and catecholamines from the adrenal gland?
Derivation:
Corticosteroids - cholesterol
Catecholamines - tyrosine
Mode:
Corticosteroids - endocrine
Catecholamines - neurocrine
Storage:
Corticosteroids - synthesised and released
Catecholamines = stored in vesicles before release
What is the difference between the effect of a bilateral adrenalectomy on corticosteroids and catecholamines?
Corticosteroids - patient must receive cortisol and aldosterone otherwise will die
Catecholamines - no apparent ill effects of lack of adrenal catecholamines
What are the different layers of the adrenal cortex and explain their biological function.
- Zona Glomerulosa. The cells in this outermost zone secrete the mineralocorticoids (e.g. aldosterone) that regulate body Na+ and K+ levels. (SALT)
- Zona Fasciculata. The cells in this zone produce the glucocorticoids (e.g. cortisol) that have a number of important functions including the regulation of carbohydrate metabolism. (SUGAR)
- Zona Reticularis. This is the deepest cortical zone and the cells secrete glucocorticoids and small amounts of androgens (dehydroepiandrosterone).
(SEX)
