Adrenal Glands Flashcards
Anatomy of adrenal glands
5cm wide
3cm tall
10g
Encapsulated w/ in the renal fascia
Pyramidal shape
Label
(include what type of hormone each secretes)
what do u call hormones of the adrenal cortex?
Corticosteroids!
- Gluco>> impotant in glucose metabolism!*
- mineralo>>important for our minerals*
Embryonic development of the adrenal cortex and medulla
Adrenal cortex is derived from the Mesoderm Medulla from the neural crest (like a walnut) , which push into the developing cortex and settle deep.
where is E and NE released from? percentage of release from each?
chromaffin cells in the Adrenal medulla!
A>>80%
NA>> 20%
aldosterone function where is it produced, what type of hormone is it? how is it transported in blood?
Zone glomerulosa>> mineralcorticoid Controls BV
1) UPREGULATES the expression of the basolateral Na/K pump on principal cells of the collecting duct and distal tubule (3 Na in, 2 K out)
2) UPREGULATES expression of epithelial Na channels ENaCs in the collecting duct and colon, allowing Na reabsorption
mainly Albumin>> lesser transcortin
Cortisol structure, type of hormone, how is it formed
PRIMARY GLUCOCORTICOID!
It comes from the steroid family, therefore it is lipophillic and is made from cholestrol.
Control of cortisol secretion?
CRF (cortisol releasing factor made in hypothalamus) >>controls ACTH secretion from corticotropes of anterior pituitary>> control cortisol secretion from zone Fasciculata
What is CRF where is it made? What stimulates its release
Cortisol releasing Factor. 41 aa made in the hypothalamus. Released due to Temp, pain, Hypoglycemia, Emotional stressors
When does cortisol peak?
Peaks in morning at 7.00am Drops at 7.00pm ** be careful when u want to take a sample fro blood cortisol measurements!
Cortisol Functions
Ok
Where is ACTH made, how is it made?
Precursor of POMC
Then post-translationol modifications of POMC at different sites produces a variety of active peptides>> a-MSH, ACTH, endorphins
The MSH is contained within the ACTH giving it some MSH-like activity!
Half life of ACTH, when doe sit peak? How is it released
Short half life of 8 mins Released in pulses following a circadian rhythm Peaks in early hours of morning
How is cortisol transported in the blood?
Bc its lipophillic, it needs to be bound to a plasma protein
90%>> Transcortin (CBG)
10%>> Albumin
Mechanism of action of cortisol upon targets cells
Cortisol crosses pm of target cells and bind to cytoplasmic receptors.
The hormone/receptor complex enters the nucleus to interact with specific regions of DNA.
This interaction changes the rate of transcription of specific genes and may take time to occur.
Actions of cortisol on target cells
Ok
The major effects of cortisol r in the ________ and_________ states
Starved and stress
Major Metabolic function of cortisol
Works in starved and stressed states:
Increased Lipolysis,
Gluconeogenesis
Proteolysis
glycogenolysis
lipogenesis
CORTISOL X insulin! It doesnt want glucose to be stored!
Cortisol has directs effects on what tissueS?
Cardiac muscle, immun system, bone
How r catecholamines made?
(Step by step Alaa, include NA and A in ur anwers plz)
Types of Adrenocepters? and what each Gprotein they act on?
Subtypes of B adrencepters
B1 B2 B3 Works on Gs
Cushings sydrome
exogenous and endogenous causes (3)?
term for Chromaffin cell tumour
How can this tumor effect the adrenal glands?
what r the characteristics?
Phaechromocytoma
Overproduction of adrenaline from adrenal medulla
Define the RAAS system? Alaa review the RAAS system okay?
System of hormones involved in regulation of plasma NA + concentration and arterial BP
Functions of Angiotensin 2
Gam yisabab tension
- vasoconstrictor
- stimulates aldosterone release
- stimulates ADH release>> translocates aquaporins in plasma membrane of collecting duct Increases BP and BV basically
- stimulates thirst mechanism
Where on the kidney does aldosterone stimulate
Distal tubule and collecting duct!
What is the most widely used drug in the RAAS system
ACE inhibitors
What disease causes an excess of cortisol secretion
Cushing syndrome
HYperactivity of the andrenal cortex giving rise increased secretion of cortisol is….
Cushings syndrome
What can cause hyperactivity of the Adrenal glands?
-Adrenal adenoma tumour -ectopic secretion of ACTH from a tumour at a site remote from the pituitary (ex; small cell tumour of the lung)
Signs and symptoms of cushings
What causes the purple striae symptom in cushings?
It reflects the catabolic effects on protein structures in the skin
Lallsy check out clinical effects of cortisol secretion in the workbook okay babes
Ok
The signs and symptoms of excess cortisol occurs in which type of patients (Think about it lulls)
They occur in patients who r taking long term treatment w/ glucocorticoids for chronic inflammatory conditions!
Ex: prednisone, hydrocortisone
Which drugs can cause the symptoms seen in excess cortisol?
HYdrocortisone and prednisone
Cushing syndrome vs Cushings disease Which of the 2 is most common?
Cushing syndrome>>general symptoms resulting from excess cortisol
Cushings Disease>> Refers to the case of a specific Benign ACTH secreting pituitary adenoma!! (Disease>>aDenoma)
CUSHINGS SYNDROME!
What is Addisons disease?
symptoms and why they occur
A conditions where ur adrenal glands ain’t workin (Decreased activity of adrenal gland) ACTH increases
Insidious onset with initial non-specific symptoms of tiredness, extreme muscular weakness, anorexia, vague abdominal pain, weight loss and occasional dizziness.
Extreme muscular weakness and dehydration.
A more specific sign is increased skin pigmentation, particularly on exposed areas of the body, points of friction, buccal mucosa, scars and palmar creases. This is due to an increase in ACTH as well as other products of POMC (α-MSH and γ-MSH) all of which stimulate melanocytes to produce more melanin.
Low blood pressure>>sodium and fluid depletion.
Postural hypotension >>fluid depletion.
Hypoglycaemic episodes especially on fasting due to lack of glucocorticoid.
common cause of addisons? who is more at risk
potential iatrogenic cause of Addison’s disease?
distructive atrophy from autoimmune diseases!
women
adrenelectomy
Decreased activity of the adrenal Cortex can be due to : (2)
- Diseases of the Adrenal cortex (auto-immune destruction)>>reduction in Glucocorticoids and minerslcorticoids
- Disroders of hypothalamus and pitaurty that lead to decreased secretion of ACTH or CRF-effects glucocorticoids
What is meant by Addisonian crisis? How do u treat it?
so important for exam alaa!
Seroius medical emeregency due to severe adrenal insufficiency
- Rapid rehydration w/ fluids
- IV hydrocortisone
- correction of hypoglycemia
What infection is highly associated w/ causing addisons disease?
TB!! Casaeous granuloma Lols
What is waterhouse-friderichsen syndrome?
Acute adrenal imsuffciency due to adrenal hemmorhage associated with septecemia (usually nessaria meningitis), DIC, shock
Explain the Hypothalamic- Pituitary-Adrenal Axis
when conditions would u use steroid drugs? give 2 examples!
in cushings syndrome w/ elevated ACTH
how can u tell what and where the cause is?
by cortisol supression test,
u give synthetic cortisol (man made) to patient and cortisol would negative feedback on pituatry and inhibit its ACTH secretion .
if it worked> porblem is with piutary! “cushings D.”
if not> its probabyl elsewhere in the body “ectopic tumors”
what r the 2 main androgens>? where r they released? what regulates their releasa
Zona reticularis!
DHEA and Androstenedione
DHEA is converted to testosterone in males!
ACTH
what is the diagnosis?
explain the reason behind each abnormality
which disease would u get hyperpigmentation and why?
Addison’s will result in a high ACTH due to removal of negative feedback of cortisol on the hypothalamic pituitary axis.
To make more ACTH, more POMC is produced and as a consequence of this more MSH
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 also contribute to the hyperpigmentation.
the deeper it goes the more exciting it gets…..
congenital adrenal hyperplasia! (CAH)
presentation?
which enzyme in the pathway of steroid synthesis, if deficient, can cause
21 hydroxylase!
u cant make miberalocorticoids or Glucortocoids, and the reaction is forced to make more Sex steroids!
Congenital Adrenal Hyperplasia!
presentation?
Treatment?
how r steroids formed? what type of recepters do they bind to?
Name 5 steriod hormones!
synthesized from cholestrol in adrenal glands.
theyre lipid soluble! they bind to Nuclear recepters
“GAME pro”
• Glucocorticoids
• Mineralocorticoids • Androgens
• Oestrogens
• Progestins
what 3 things leads to more renin release from kidney
- Decrease in renal perfusion
- Drop in blood pressure
- increased sympathetic tone from baroreceptor activation
what is conn’s syndrome?
treatment?
Adrenal Adenoma secreting too much aldosterone
aldosterone antagonists! >>SPIROLACTONE!
Hyperaldosteronism, there is primary and secondary
Explain them! treatment?
how can u tell wether it s aprimary or secondary?
by looking at renin levels!
effects of cortisol on fat?
Lipolysis
BUTTTT> if you’ve got chronic levels of cortisol in the blood….
u get this redistribution (deposition) of fat in the abdomen, supraclavicular fat pads and dorsoclavicular fat pads
causing Moon face and bufflo hump!
how does cortisol inhibit glucose uptake in muscle?
it inhibits insulin-induced GLUT 4 Translocation in muscle!
what is an example of a non-pituitary adrenal tumour (tumor elsewhere in the body, (ectopic) that can cause cushings syndrome?
small cell lung cancer!
explain the symptoms of cushings sydrome and explain why they occur?
- muscle proteolysis and hepatic gluconeogenesis >> hyperglycaemia with associated polyuria and polydipsia (“steroid diabetes”).
- muscle proteolysis>>>wasting of proximal muscles and producing thin arms & legs & muscle weakness.
- lipogenesis in adipose tissue leading to deposition of fat in abdomen, neck and face and producing characteristic body shape, moon-shaped face and weight gain.
- Purple striae >> catabolic effects on protein structures in the skin leading to easy bruising because of thinning of skin and subcutaneous tissue.
- Immunosuppressive>>increased risk to bacterial infections and producing acne.
- May be back pain and collapse of ribs due to osteoporosis caused by disturbances in calcium metabolism and loss of bone matrix protein.
- hypertension due to sodium and fluid retention.
Would you expect the aldosterone:renin ratio to be high or low in a patient with secondary hyperaldosteronism caused by renal artery stenosis?
Low
dunno why tho
What is the mode of action of the drug spironolactone?
Mineralocorticoid receptor antagonist
Explain why purple striae as depicted in the patient below are often seen in Cushing’s syndrome?
The central obesity from the cortisol induced redistribution of fat in Cushing’s syndrome stretches the skin. Since the skin is thin and weakened due to the actions of cortisol also increasing proteolysis, “stetch marks” or purple striae can form.
A tumour of which cell type is called a pheochromocytoma?
A tumour of Chromaffin cells in the adrenal medulla is called pheochromocytoma.
Such tumours secrete catecholamines (mostly noradrenaline) resulting in symptoms such as severe hypertension, headaches, palpitations excessive sweating, anxiety and weight loss.
In which region of the adrenal gland is dehydroepiandrosterone (DHEA) mostly produced?
Which type of enzyme catalyses the conversion of noradrenaline to adrenaline?
Methyl transferase
what r some clinical tests for Adrenocortical function?
measurment of plasma cortisol and ACTH levels & the 24hr urinary excretion of cortisol and its breakdown products r important .
Dynmaic funciton test>> ex: dexamthasone suprresion test, ACTH stimulation test/
Which exogenous steroid is typically administered in a supression test to diagnose Cushing’s syndrome?
dexamethasone
what is Dexamethasone?
synthetic steroid, when given orally, should supress the secretion of ACTH and thus cortisol.
used for the supression test!
what is synacthen? what happens if u adminster it IM?
synthetic analogue of ACTH
The administration of Synacthen intramuscularly, would normally increase plasma cortisol by >200 nmol/L. A normal response usually excludes Addison’s disease.
what is this?
what causes it?
Hirsutism
over secretion of the adrenal androgens produces effects in the female that include:
excessive hair growth, acne , menstrual problems, corse voice, bulky msucles
estrogens decrease circulating cholestrol levels!
ok
which structure in the Adrenal gland has a function towards the ANS?
what is this function
Adrenal medulla
its a modified Sympatheic Ganglion of the ANS
Chromaffin cells LACK AXONS THO, but act as postganglionic nerve fibers that release hormones into the blood!
how does adrenaline increase HR?
biochemical test fro adrenla cortex/medulla?
what certain foods should ur patient avoid before taking collection?
Adrenal cortex
- Electrolyes (Na and K)
- Basal cortisol at 9am
- stimulation test (inject ACTH and see if cortisol levels rise)
Adrenal medulla
- 24hr urine catecholamines
- 24hr urine Metanephrines (which r breakdown products of Adreniline)
- blood metanephrines
Coffee, coke, bananas, choco, vanilla
what are some Radiological tests u can carry out?
Pet scan
CT
MIBG
causes of primary adrenal failure?
- Auto-immune isolated or polyglandular
- Infection TB, fungal, AIDS
- Infiltration amyloid, haemochromatosis
- Malignancy lung, breast, kidney
- Genetic CAH, adreno-leukodystrophy
- Vascular haemorrhage or infarction
- Iatrogenic adrenalectomy, drugs
Nelson’s syndrome?
Nelson’s syndrome is a rare disorder that occurs in patients who had both adrenal glands removed.
The patient develops macroadenomas that secrete ACTH.
Outline the major structural differences between the various classes of steroid hormones.
- -# of C atoms
- -distribution of C double bonds
- -presence of functional groups
In female adrenal androgens promote——— and are converted to _________ by other tissues.
libido
estrogens
******After menopause this is only source of oestrogens.
this is the test of someone with cushings.exaplin the differences in Na and K levels
Cortisol in high amount can ib kaif uma go and act on aldosterone recepters cause Na reabsorption and K excretion!
- the actions of cortisol on target tissues are mediated by binding to receptors in the cytoplasm/nucleus. All steroid hormone receptors have similar basic structure with hormone and DNA binding domains.*
- The hormone binding domains of the mineralocorticoid and androgen receptors have over 60% sequence homology with the hormone-binding domain of the glucocorticoid receptor. Thus, cortisol can bind to these receptors to a limited extent causing their partial activation*
Explain why high circulating levels of ACTH can lead to increased pigmentation in certain areas of the body.
Pigment (melanin) production by melanocytes is activated by the hormones MSH (Melanocyte stimulating hormone). The initial biosynthetic precursor of ACTH is called pro-opiomelanocortin (POMC).
Post-translational processing of POMC at different sites produces a range of biologically active peptides including ACTH and MSH.
The MSH sequence is contained within the ACTH sequence in POMC giving ACTH some MSH-like activity when present in excess.
The clinical consequences of over-secretion of ACTH therefore include increased pigmentation due to partial MSH activity.
what is androgenic alopecia?
hair loss
