Adrenals

Question 1

How are the adrenals perfused?

Answer 1

Left adrenal vein drains into renal vein
Right adrenal vein drains into IVC
Many arteries but ONE vein each

Question 2

Where are the adrenal glands found?

Answer 2

Embedded on superior pole of each kidney, with own capsules

Question 3

What is the structure of the adrenal glands?

Answer 3

Pyramidal shape
Surrounded by tough and fibrous capsule
Adrenal cortex:
-Zona glomerulosa
-Zona fasciculata
-Zona reticularis
Adrenal medulla

Question 4

What is produced in the adrenal medulla?

Answer 4

Catecholamines - 80% circulating adrenaline, 20% noradrenaline neurotransmitter

Question 5

What is produced in the different layers of the adrenal cortex?

Answer 5

Corticosteroids - mineral, glucocorticoids and sex steroids
Zona glomerulosa - aldosterone
Zona fasciculata - Cortisol + small amounts of androgens and oestrogen
Zona reticularis - androgens and oestrogen

Question 6

How are hormones drained from the adrenal glands?

Answer 6

Tributaries of the central vein drain all hormones from medulla

Question 7

Which cells produce catecholamines and where?

Answer 7

Chromaffin cells in the adrenal medulla

Question 8

What is the precursor for all steroid hormones?

Answer 8

Cholesterol -> pregnenolone

Question 9

What are features of steroid hormones?

Answer 9

Lipid soluble, very powerful

diffuse straight into target cells

Question 10

What happens to cholesterol prior to it entering the steroidogenic pathway?

Answer 10

Sythesised and packaged into lipoproteins
Lipoproteins deliver cholesterol for storage in fat droplets as fatty esters
Liberated by esterase, producing cholesterol to enter mitochondria using StAR protein
Cholesterol then enters the steroidogenic pathway

Question 11

How is cortisol synthesised?

Answer 11

Cholesterol→prenenolone→intermidiates→ cortisol

Question 12

How is aldosterone synthesised?

Answer 12

Cholesterol→pregnenolone→ progesterone→deoxycorticosterone→ corticosterone and aldosterone

Question 13

How are sex steroids synthesised?

Answer 13

extra enzymes lead to production of testosterone and oestradiol

Question 14

How is the production of cortisol triggered?

Answer 14

Hypothalamus produces corticotrophin releasing hormone, which enters the primary plexus and leaves at the secondary to bind to corticotrope cells
Corticotrophic cells produce adrenocorticotrophic hormone (ACTH)
ACTH travels in blood to adrenal cortex and binds to receptors to activate esterase/StAR proteins
This causes influx of cholesterol in order for steroidogenesis

Question 15

How is aldosterone transported around the body?

Answer 15

In the blood
40% as free hormone - bioactive
15% bound to Corticosteroid binding globulin
45% bound to albumin

Question 16

How is cortisol transported in the body?

Answer 16

In the blood
10% as free hormone - bioactive
80% bound to corticosteroid binding globulin
10% bound to albumin

Question 17

What are the actions of cortisol?

Answer 17

Increases:
-gluconeogenesis
-protein catabolism
-lipolysis (reduced lipoprotein lipase)
Enhances effects of glucagon and catecholamines
decreases glucose uptake∴increases plasma glucose
Upregulates serotonin receptors-improves memory
Surpra-physiological:
-anti-inflammatory
-anti-allergic
-immunosuppressive

Question 18

What are the actions of aldosterone?

Answer 18

Increases sodium reabsorption in the distal nephron
∴Increases water retention
leads to increased BP

Question 19

What are the differences between the production of cortisol and aldosterone?

Answer 19

More cortisol produced in the morning than evening
Cortisol production 1000x more than aldosterone
Aldosterone never high enough in blood to out-compete cortisol

Question 20

How and why does aldosterone convert cortisol to cortisone?

Answer 20

Activates 11-beta-HSD2
Protects certain tissues from cortisol so only aldosterone can bind to mineralocorticoid receptors e.g. kidney and placenta

Question 21

What receptors can cortisol bind to?

Answer 21

Glucocorticoid receptors and minceralocorticoid receptors

Question 22

What receptors can aldosterone bind to?

Answer 22

Mineralocorticoid receptors

Question 23

How are adrenal secretions controlled?

Answer 23

Renin-angiotensin-aldosterone system

Question 24

What are juxtaglomerular cells and where are they found?

Answer 24

Line afferent arteroile leading to the proximal convoluted tubule in kidneys
Specialised smooth muscle cells that can release renin enzymes when BP decreases
Stimulated by sympathetic nerves

Question 25

What are macula densa cells and where are they found?

Answer 25

Present in distal convoluted tubule and can sense sodium
When low pressure, more sodium reabsorbed so less reaches DCT
Causes macula densa cells to release protaglandins to stimulate juxtaglomerular cells to produce renin

Question 26

What is renin?

Answer 26

Enzyme released into blood steam by juxtaglomerular cells

Released to bloodstream to cleave angiotensinogen produced by liver

Question 27

How is aldosterone produced?

Answer 27

Angiotensinogen produced by liver
Renin catalyses conversion of angiotensinogen to angiotensin I
Blood then enters lungs, allowing angiotensin converting enzyme to convert angiotensin I to angiotensin II
Angiotensin II enters zona glomerulosa of adrenal cortex and stimulates aldosterone production

Question 28

When is renin secreted?

Answer 28

Decreased renal perfusion pressure
Increased renal sympathetic activity
Low sodium at top of loop of Henle detected by macula densa cells

Question 29

What are the actions of angiotensin II?

Answer 29

Constriction of glomerular efferent arteriole and increase in Na+/H+ exhanger activity
Increased ADH secretion from posterior pituitary
Constriction of vascular smooth muscle
Stimulates thirst in hypothalamus
Aldosterone secretion from the adrenal zona glomerulosa

Question 30

What is the method of action of aldosterone?

Answer 30

Aldosterone binds to mineralocorticosteroid receptors intracellularly, increasing transcription of proteins involved in Na+ reabsorption
Increases the number of sodium channels on the distal tubule cells ∴ influx to the cells from the lumen
Also increases number of Na+/K+ ATPase pumps on the basolateral membrane, allowing Na+ to be transported to the interstitium to maintain the Na+ concentration gradient
Low blood Na+/BP activates renin-angiotensin system
Causes water reuptake as this requires Na+’s osmotic gradient

Question 31

What is the method of action of cortisol?

Answer 31

Binds intracellularly to glucocorticoid receptors
Increases gluconeogenesis in liver
Increases lipolysis
Decreases GLUT4/lipoprotein lipase in peripheral tissue to prevent glucose and NEFAs entering muscle
Upregulates serotonin receptors for pro-memory effects because stress/cortisol wants to imprint memory

Question 32

What are the supra-physiological actions of cortisol?

Answer 32

Anti-inflammatory/immunosuppressive effects
Reduces leukocyte/lymphocyte function, histamine reactions and complement levels
Chronically high cortisol reduces function of immune system
High levels of cortisol chronically leads to full MR and GR activation = anti memory effects, working against serotonin to produce impaired memory and hippocampus shrinkage

Question 33

How does the hypothalamo-pituitary-adrenal axis cause cortisol release?

Answer 33

1) Hypothalamus secretes corticotropin releasing hormone to the 1°plexus and it enters anterior pituitary @2° plexus
2) CRH stimulates corticotrope cells to synthesise POMC
3) POMC cleaved to ACTH, melanocyte stimulating hormone cortex and endorphins
3) ACTH enters adrenal gland cortex, binds to receptors and causes PKA activation and ∴ esterase/StAR activation
4) Cortisol is produced in the mitochondrial steroidogenic pathway

Question 34

How is cortisol regulated?

Answer 34

Cortisol exerts a direct -ve feedback loop to the hypothalamus and on the pituitary gland, reducing CRH and ACTH production

Question 35

What is a sign of excess ACTH in the system?

Answer 35

Tanning due to increase in melanocyte stimulating hormone produced when ACTH is produced

Question 36

What are the most common causes of 1° adrenal failure?

Answer 36

Autoimmune destruction of adrenal cortex UK

TB infection in adrenal glands GLOBAL

Question 37

What are the clinical features of 1° adrenal failure/Addison’s disease?

Answer 37

Generalised weakness and hypotension due to loss of Na+ - hyponatraemia
Adrenal atrophy
Increased and inappropriate pigmentation
Hyperkalaemia 
XS MSH and ACTH in blood

Question 38

How would you treat a person having an Addinsonian crisis?

Answer 38

Rehydrate with normal saline
Give dextrose to prevent hypoglycaemia - glucocorticoid deficiency
Give hydrocortisone or another glucocorticoid medication

Question 39

What are the causes of Cushing’s syndrome?

Answer 39

Excess cortisol/glucocorticoid caused by:
Oral steroid intake
Pituitary adenoma producing XS ACTH
Ectopic ACTH e.g. from lung cancer cells
Adrenal adenoma/cacinoma

Question 40

What are clinical signs of Cushing’s syndrome?

Answer 40

Weight gain (more fat less protein)
Thin skin, easy bruising
Proximal myopathy
Striae
Hypertension
Fat redistribution - lemon on sticks
Moon face
Hirsutism and acne

Question 41

What is the cause of Conn’s syndrome?

Answer 41

Tumour of the zona glomerulosa

Question 42

What are the clincal features of Conn’s syndrome?

Answer 42

Adenoma that produces aldosterone
Aldosterone leads to sodium retention and loss of potassium
Hypertension
Oedema
Hypokalaemia