Adrenals Flashcards
Adrenal structure; Adrenal corticosteroids; Hypothalamo-pituitary-adrenal axis; Primary adrenal failure; Cushing's syndrome; Conn's syndrome
How are the adrenals perfused?
Left adrenal vein drains into renal vein
Right adrenal vein drains into IVC
Many arteries but ONE vein each
Where are the adrenal glands found?
Embedded on superior pole of each kidney, with own capsules
What is the structure of the adrenal glands?
Pyramidal shape Surrounded by tough and fibrous capsule Adrenal cortex: -Zona glomerulosa -Zona fasciculata -Zona reticularis Adrenal medulla
What is produced in the adrenal medulla?
Catecholamines - 80% circulating adrenaline, 20% noradrenaline neurotransmitter
What is produced in the different layers of the adrenal cortex?
Corticosteroids - mineral, glucocorticoids and sex steroids
Zona glomerulosa - aldosterone
Zona fasciculata - Cortisol + small amounts of androgens and oestrogen
Zona reticularis - androgens and oestrogen
How are hormones drained from the adrenal glands?
Tributaries of the central vein drain all hormones from medulla
Which cells produce catecholamines and where?
Chromaffin cells in the adrenal medulla
What is the precursor for all steroid hormones?
Cholesterol -> pregnenolone
What are features of steroid hormones?
Lipid soluble, very powerful
diffuse straight into target cells
What happens to cholesterol prior to it entering the steroidogenic pathway?
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
How is cortisol synthesised?
Cholesterol→prenenolone→intermidiates→ cortisol
How is aldosterone synthesised?
Cholesterol→pregnenolone→ progesterone→deoxycorticosterone→ corticosterone and aldosterone
How are sex steroids synthesised?
extra enzymes lead to production of testosterone and oestradiol
How is the production of cortisol triggered?
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
How is aldosterone transported around the body?
In the blood
40% as free hormone - bioactive
15% bound to Corticosteroid binding globulin
45% bound to albumin
How is cortisol transported in the body?
In the blood
10% as free hormone - bioactive
80% bound to corticosteroid binding globulin
10% bound to albumin
What are the actions of cortisol?
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
What are the actions of aldosterone?
Increases sodium reabsorption in the distal nephron
∴Increases water retention
leads to increased BP
What are the differences between the production of cortisol and aldosterone?
More cortisol produced in the morning than evening
Cortisol production 1000x more than aldosterone
Aldosterone never high enough in blood to out-compete cortisol
How and why does aldosterone convert cortisol to cortisone?
Activates 11-beta-HSD2
Protects certain tissues from cortisol so only aldosterone can bind to mineralocorticoid receptors e.g. kidney and placenta
What receptors can cortisol bind to?
Glucocorticoid receptors and minceralocorticoid receptors
What receptors can aldosterone bind to?
Mineralocorticoid receptors
How are adrenal secretions controlled?
Renin-angiotensin-aldosterone system
What are juxtaglomerular cells and where are they found?
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
What are macula densa cells and where are they found?
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
What is renin?
Enzyme released into blood steam by juxtaglomerular cells
Released to bloodstream to cleave angiotensinogen produced by liver
How is aldosterone produced?
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
When is renin secreted?
Decreased renal perfusion pressure
Increased renal sympathetic activity
Low sodium at top of loop of Henle detected by macula densa cells
What are the actions of angiotensin II?
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
What is the method of action of aldosterone?
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
What is the method of action of cortisol?
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
What are the supra-physiological actions of cortisol?
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
How does the hypothalamo-pituitary-adrenal axis cause cortisol release?
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
How is cortisol regulated?
Cortisol exerts a direct -ve feedback loop to the hypothalamus and on the pituitary gland, reducing CRH and ACTH production
What is a sign of excess ACTH in the system?
Tanning due to increase in melanocyte stimulating hormone produced when ACTH is produced
What are the most common causes of 1° adrenal failure?
Autoimmune destruction of adrenal cortex UK
TB infection in adrenal glands GLOBAL
What are the clinical features of 1° adrenal failure/Addison’s disease?
Generalised weakness and hypotension due to loss of Na+ - hyponatraemia Adrenal atrophy Increased and inappropriate pigmentation Hyperkalaemia XS MSH and ACTH in blood
How would you treat a person having an Addinsonian crisis?
Rehydrate with normal saline
Give dextrose to prevent hypoglycaemia - glucocorticoid deficiency
Give hydrocortisone or another glucocorticoid medication
What are the causes of Cushing’s syndrome?
Excess cortisol/glucocorticoid caused by: Oral steroid intake Pituitary adenoma producing XS ACTH Ectopic ACTH e.g. from lung cancer cells Adrenal adenoma/cacinoma
What are clinical signs of Cushing’s syndrome?
Weight gain (more fat less protein) Thin skin, easy bruising Proximal myopathy Striae Hypertension Fat redistribution - lemon on sticks Moon face Hirsutism and acne
What is the cause of Conn’s syndrome?
Tumour of the zona glomerulosa
What are the clincal features of Conn’s syndrome?
Adenoma that produces aldosterone Aldosterone leads to sodium retention and loss of potassium Hypertension Oedema Hypokalaemia
