The adrenal gland Flashcards
Where are the adrenal glands situated?
Above the right and left kidneys
How is the blood supply of the adrenal gland organised?
Have many arterial connections but only 1 vein each
Left adrenal vein drains into renal vein
Right adrenal vein drains into IVC
How is the adrenal gland structured?
Phrenic fascia encloses adrenal glands and kidneys
Adrenal gland consists of outer connective tissue capsule, cortex and medulla
What is the cortex derived from?
embryonic mesoderm
What is the medulla derived from?
ectodermal neural crest cells
What is the role of the adrenal cortex?
Secretes cholesterol derived hormones: corticosteroids and androgens
What 3 regions is the cortex divided into and what hormones does it secrete?
Zona glomerulosa: mineralocorticoids- aldosterone
Zona fasciculata: glucocorticoids - cortisol
Zona Reticularis: androgens and oestrogen
What is the role of the adrenal medulla?
Contains chromaffin cells which secrete catecholamines into systemic circulation in response to stress
What catecholamines are there?
Adrenaline (80%) and noradrenaline (20%)
What hormones are derived from cholesterol?
Mineralocorticoids, glucocorticoids, androgens and oestrogen
How is progesterone derived?
Cholesterol is converted to pregnenolone through a side chain cleavage
3- beta hydroxy steroid dehydrogenase oxidises hydroxyl group forming ketone group
This converts pregnenolone to progesterone
How is aldosterone produced?
21- hydroxylase converts progesterone to 11-deoxycorticosterone
11- hydroxylase then converts this to corticosterone
18- hydroxylase converts corticosterone to aldosterone
How is cortisol produced?
Progesterone is converted by 17- hydroxylase to 17- hydroxy-progesterone
21 hydroxylase converts this to 11-deoxycortisol
11 hydroxylase converts this to cortisol
How is oestrogen produced?
Progesterone is converted by 17- hydroxylase to 17- hydroxy-progesterone
this is converted to sex steroid which are converted to androgens and then oestrogen
What is the process of deriving hormones from cholesterol called?
Steroidgenesis
How is cortisol transported through the body?
Cortisol is bound to corticosteroid binding globulin (75%), albumin (15%) and 10% is in the bioactive form and is unbound
What system makes aldosterone?
Renin- angiotensin system
What is the role of aldosterone?
Stimulates Na+ resorption in distal convoluted tubule (DCT) and cortical collecting duct (CCD)
Stimulates K+ and H+ secretion in DCT and CCD- lowers blood K+ levels
Increases water resorption (stimulates vasopressin) and increases blood volume and blood pressure
Through what mechanisms does aldosterone work?
Aldosterone is cell membrane permeable and binds to intracellular receptors
Hormone receptor complex goes to nucleus where it acts as a transcription factor and binds to promotor regions on DNA- this leads to mRNA transcription and translation of ion pumps and enzymes
Aldosterone stimulates synthesis of Na+ channels in apical membrane
What is renin released by?
Beta- adrenoreceptors on juxta-glomerular cells (cells which line ascending loop of Henle) release renin
What 3 stimuli cause the release of renin?
- Decreased arterial blood pressure (decreased renal perfusion pressure)
- Increased renal sympathetic activity
- Decreased Na+ load to top of loop of Henle
What is the renin- angiotensin system?
Liver secretes angiotensin
Renin cleaves angiotensin to angiotensin I
Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II
What is the role of angiotensin II?
Stimulates zona glomerulosa to produce aldosterone (stimulates enzymes needed: 3-beta- HSD, 21, 11 and 18- hydroxylase
REGULATES ALDOSTERONE RELEASE
What are effects of cortisol?
Normal stress response
Stimulates peripheral protein catabolism (break down protein)
Hepatic gluconeogeneisis
Increases blood glucose conc.
Fat metabolism
Enhances effects of glucagon and catecholamines (Adrenaline and noradrenaline)
Weak mineralocorticoid effects (aldosterone)
Excretion of water load
Increased vascular permeability
What controls cortisol release?
ACTH is released when stimulated by corticotrophin releasing hormone (anterior pituitary)
This stimulates release of cortisol
High cortisol levels lead to decrease in ACTH release which decreases CRH in hypothalamus (negative feedback)
This is known as the hypothalamic-pituitary- adrenal axis
How do cortisol levels change through the day?
Has a diurnal rhythm
This is a circadian rhythm
What is Addison’s disease?
Autoimmune disease where the immune system destroys the adrenal cortex
TB bacteria in the adrenal glands (comment cause of primary adrenal failure)
Pituitary starts secreting lots of ACTH and hence MSH (melanocyte stimulating hormone)
What are symptoms of Addisons disease and what causes them?
- Low blood pressure and hyponatremia (salt deficiency): reduced cortisol and aldosterone
- Hyperkalaemia (increased K+): decreased aldosterone
- Increased pigmentation and bronze pallor: Pro-opio-melanocortin is cleaved to form ACTH and MSH and endorphins. Increased POMC leads to increased ACTH which leads to increased MSH
- Autoimmune vitiligo may coexist
- Metabolic acidosis: H+ ion increase. Postural hypotension can lead to reduced blood flow to brain
- Hypoglycaemia: reduced cortisol so reduced catecholamines
- Infertility: reduction in sex steroids
How can Addison’s disease cause death?
Cortisol deficiency Aldosterone deficiency Salt loss Low blood pressure Death
How do you treat Addison’s disease?
Rehydrate with normal saline
Give dextrose to prevent hypoglycaemia
Give hydrocortisone or another glucocorticoid (cortisol or prednisolone- artificial steroid that is longer lasting and only has to be given once a day)
What is Cushing’s syndrome?
Concerned with elevated levels of cortisol primarily due to adrenal gland tumour (makes cortisol) or pituitary gland tumour (makes ACTH)
Theres increased secretion of ACTH so increased secretion of cortisol
Increased cortisol changes metabolism and causes weight gain- protein converted to fat
What are symptoms of Cushing’s syndrome?
Impaired glucose tolerence (diabetes)
High BP
Proximal myopathy (muscle weakness)- thins arms and legs and osteoporeisis
Fat pads (buffalo humps)- fat between scapulae which is uncommon
Mental changes
Skin changes: (due to less protein) bruising, think skin, red cheek, red stretch marks, moon face
Centripetal obesity
What are 4 possible causes of Cushing’s syndrome?
- Taking steroids (glucocorticoids) orally
- Pituitary dependent Cushing’s disease (pituitary adenoma)
- Ectopic ACTH (lung cancer)
- Adrenal adenoma or carcinoma
How are catecholamines made?
Tyrosine is converted to dopa which is converted to dopamine
Dopamine is hydroxylated to form norepinephrine (noradrenalin)
Methyl group is added to narepinephrin to make epinephrin (Adrenalin)
What is the function of catecholamines?
Fight or flight- tachycardia, sweating, increased blood glucose, vasoconstriction
How are catecholamines carried around the blood?
They’re bound to albumin
How are catecholamines degraded?
Degraded by 2 hepatic enzymes:
Monoamine oxidase and catechol-O-methyl transferase
