17 Adrenal Glands Flashcards
Where are the adrenal glands located?
On top of kidneys- attached to diaphragm
What are the main components which make up the adrenal glands?
- Capsule
- Cortex
- Medulla
What layers make up the cortex of the adrenal glands?
Zona glomerulosa, zona fascicolata, zona reticularis
What hormone does each layer of the cortex produce?
CORTICOSTEROIDS:
1) zona glomerulosa- mineralcorticoids (SALT)
2) zona fasiculata -glucocorticoids (SUGAR)
3) zona reticularis- glucocorticoids+small amounts of androgens (SEX)
What cells is the medulla made up of?
Chromaffin cells
What do the chromaffin cells produce?
80% Adrenaline, 20% Noradrenaline
What are steroid hormones synthesised from?
Cholesterol
How do steroid hormone function?
=Lipid soluble–> bind to nuclear receptors–> modulate gene transcription
Give examples of steroid hormones.
Glucocorticoids
Mineralocorticoids
Androgens
Oestrogen
Progestins
How do corticosteroids exert their actions?
1) Diffuse across plasma membrane
2) Bind to glucocorticoid receptors- cause dissociation of CHAPERONE PROTEINS
3) Receptor ligand translocates to nucleus- receptors bind to glucocorticoid response elements:
* (GREs)/transcription factors*
Name the most abundant mineralocorticoid.
Aldosterone
What are the carrier proteins for aldosterone?
Albumin (+transcortin)
How does aldosterone exert its effects?
- =steroid hormone
- Regulates gene transcription -intracellular
- Lipophilic
What is the function of Aldosterone?
Regulates plasma sodium and potassium- arterial blood pressure
Where in the body does aldosterone exert its actions?
DISTAL TUBULES and COLLECTING DUCTS of NEPHRON
Promotes expression of Na+/K+ pump, promotes reabsorption of Na+ and excretion of K+
Which part of the adrenal cortex synthesises and releases aldosterone?
Zona glomerulosa
What is the RAAS (renin-angiotensin-aldosterone system)?
System that regulates :
- blood pressure
- fluid electrolyte
- balance
What organs/tissues are involved in the RAAS?
- Lungs
- Liver
- Kidney
- Adrenal glands (cortex)
- Arterioles
- Posterior pituitary
Outline how the RAAS works in 5 steps.
- Decreased renal perfusion- drop in blood pressure, increased sympathetic tone from baroreceptor activation- increased renin release from kidney
- Angiotensinogen constitutively released into blood by liver
- Angiotensinogen cleaved by renin to angiotensin I
- ACE (angiotensin converting enzyme) released in lungs cleaves angiotensin Itoangiotensin II
-
Angiotensin II causes:
- Vasoconstriction
- Adrenal Cortex releases aldosterone: Increased water and Na+reabsorption into blood (increased expression of sodium potassium pump)
- Posterior pituitary releases ADH: Translocation of aquaporin channels aids reabsorption of water back into the blood
What type of drug may be given as an antihypertensive?
ACE inhibitors
What causes primary hyperaldosteronism?
Defect in adrenal cortex eg:
- Bilateral idiopathic adrenal hyperplasia (most common)
- Conn’s syndrome: Aldosterone secreting adrenal adenoma
- LOW RENIN LEVELS= high aldosterone:renin ratio
What causes secondary hyperaldosteronism?
Overactivity of RAAS
- Renal artery stenosis
- Renin producing tumour= rare
- HIGH RENIN LEVELS (low aldosterone:renin ratio)
What’s the best way to distinguish between primary and secondary hyperaldosteronism?
High renin levels= secondary
Low renin levels= primary
What are the signs/symptoms of hyperaldosteronism?
- High BP
- Left ventricular hypertrophy
- Stroke
- Hypernatraemia
- Hypokalaemia
How might hyperaldosteronism be treated?
(Depends of type)
- Removal of aldosterone-producing adenomas
- Spironolactone=mineralcorticoid receptor antagonist
What’s the most abundant corticosteroid?
Cortisol
What hormone stimulates the synthesis and release of Cortisol from the Zona fasiculata?
Adrenocorticotropic hormone (ACTH)
What is the carrier protein for cortisol? (in plasma)
Transcortin
How does a cortisol receptor exert its effects?
Regulating gene transcription
List the actions of cortisol (6):
- Increase protein breakdown in muscle
- Increased lipolysis in fat
- Increased gluconeogenesis in liver
- Resistance to stress (increased supply of glucose, raise BP- vessels more sensitive to vasoconstrictors)
- Anti-inflammatory effects (inhibit macrophage activity+ Mast cell degranulation)
- Depression of immune response (prescribed organ transplant patients)
Fill in the missing labels in the following diagram:
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What are the actions of glucocorticoid hormones on metabolism?
- Increased glucose production
- Breakdown of protein
- Redistribution of fat
What is cushing’s syndrome?
Chronic excessive exposure to cortisol
What are the 2 main types of causes of cushing’s syndrome?
- External (most common)
- Endogenous (rare)
What’s the most common external cause of Cushing’s syndrome?
Prescribed glucocorticoids
What are the 3 endogenous causes of Cushing’s syndrome?
- Cushing’s disease: benign pituitary adenoma secreting ACTH
- Adrenal Cushing’s: excess cortisol produced by adrenal tumour
- Non pituitary-adrenal tumours producing ACTH e.g. small cell lung cancer
Give 2 examples of steroid drugs.
- Prenisolone
- Dexamethasone
What effects does Prednisolone have?(2)
- Anti-inflammatory effects
- Immunomodulatory effects (eg supress immune reaction to organ transplantation)
What is Prednisolone used to treat?
- Asthma
- Inflammatory bowel disease
- Rheumatoid arthritis
- Other autoimmune conditions
- Supress immune reaction to organ transplant
Describe the side effects of steroid drugs like prednisolone and dexmethasone.
Same as effects of high levels of cortisol
+ can have mineral corticoid effects
Why should steroid dosage be reduced gradually and not stopped suddenly?
Down regulation due to negative feedback
What is Addison’s disease?
Chronic adrenal insufficiency
What are the causes of Addison’s disease? (5)
- Autoimmune response- causing destructive atrophy
- Complication of Tuberculosis
- (Much rarer) Fungal infection
- (Much rarer) Adrenal cancer
- (Much rarer) Adrenal haemorrhage (following trauma)
What are the signs and symptoms of Addison’s disease?
- Postural hypotension
- Lethargy
- Weight loss
- Anorexia
- Increased skin pigmentation
- Hypoglycaemia
Why might Addison’s disease cause hyperpigmentation?
- Decreased cortisol
- Negative feedback anterior pituitary reduced
- More POMC require to synthesise ACTH
- POMC increases ACTH and MSH production
- ACTH itselfactivates melanocortin receptors on melanocytes
What is the ‘Addisonian crisis’?
Life threatening emergency- due to adrenal insufficiency
What is an addisonian crisis precipitated by?
- Severe stress
- Salt deprivation
- Infection
- Trauma
- Cold exposure
- Over exertion
- Abrupt steroid drug withdrawal
What are the symptoms of an addisonian crisis?
- Nausea
- Vomiting
- Pyrexia
- Hypotension
- Vascular collapse
How do you treat an Addisonian crisi?
- Fluid replacement
- Cortisol
Where are (weak) androgens secreted from?
Zona reticularis
What androgens are secreted from the zona reticularis in the adrenal cortex?
- DHEA: Dehydroepiandrosterone
- Androstenedione
Which hormones (partially) regulate androgen release from the zona reticularis?
- ACTH
- CRH
What happens to DHEA in males?
Converted to testosterone in testes
(insignificant after puberty)
What do androgens do in females/ what happens to them?
- Promote libido
- Converted to oestrogens
(only source of oestrogens after menopause)
What do androgens do in both sexes?
Promote axillary and pubic hair growth
Decribe the Adrenal Medulla:
- Modified sympathetic ganglion fo ANS
- Chromaffin cells lack axons
- –> BUT act as post ganglionic nerve fibres–> release hormones into blood
Adrenaline 80%
Noradrenaline 20%
What receptors do adrenaline and noradrenaline act on? (and what pathways do they activated)
Fill in the gaps with the type of GPCR:
What is a Phaeochromocytoma?
Rare
Chromaffin cell tumour
Catecholamine-secreting tumour
What are the signs/symptoms of a phaeochromocytoma?
- Severe hypertension
- Headaches
- Palpitations
- Diaphoresis (excessive sweating)
- Anxiety
- Weight loss
- Elevated blood glucose
Fill in the missing gaps:
