The adrenal glands Flashcards
Where are the adrenal glands located
Upper poles of the kidneys
What are the 3 zones of the adrenal glands in a human
Zona glomerulus
Zona fasciculata
Zona reticularis
Does the adrenal gland share fascia with the kidney
No it has its own renal fascia
How do the shapes of the right and left adrenal glands differ
Right is more triangular
Left is flatter
What makes up the capsule of the adrenal glands
Fibroblasts and myofibroblasts
Where do veins and lymphatic vessels leave the adrenal glands
At the hila
What % of the adrenal gland is made up of cortex
90%
In what direction does blood flow through the adrenals
Capsule to medulla
Describe how vessels entering the adrenals appear
They form a subcapsular capillary plexus that gives rise to fenestrated sinusoids which pass through the gland
How does structure of blood vessels ensure efficiency hormone delivery
Most cells are only 1-2 cells away from vascular endothelial cell
Describe how the zona glomerulosa appears histologically
- Small, narrow cells in rounded clusters
- Deep staining nuclei and basophilic cytoplasm
- Lipid droplets
Describe how zona fasciculata cells appear histologically
Larger than ZG
Clear cells as don’t stain as much
Laid out in columns
Describe how zona reticularis appears histologically
Branching network of smaller, compact cells
What is secreted by each zone of the adrenals
ZG: aldosterone
ZF: cortisol
ZR: androgens
Describe the structure of the adrenal medulla
- Little connective tissue
- Chromaffin cells are large with large nuclei and fine cytoplasmic granules
What does the medulla secrete
Adrenalin and noradrenaline
3 kinds of stress body can experienceS
Starvation
Infection
Severe volume loss
What stimulates the release of aldosterone
High potassium
Low BP
What is the principle mineralocorticoid
Aldosterone
What is stimulated if there is haemorrhage/ sodium loss/ decreased renal perfusion
Renin from kidney
Angiotensinogen from the liver
What is the effect of ANG 2 on adrenals
Release of aldosterone and potassium moves in
Effect of aldosterone on the kidneys?
Increased sodium reabsorption and potassium secretion
This leads to h20 resorption which restores circulating volume
What is the effect of aldosterone on the vessels
Vasoconstriction and remodelling
2 molecules that can bind to mineralcorticoid receptor, and 1 that can’t
Cortisol and aldosterone can
Cortisone can’t
Describe how aldosterone acts on the kidney at a cellular level
- Stimulates Na/K ATPase
- Increases expression
- Inserts additional ENaC
- Stimulate H+ ATPase
What is Conn’s syndrome
Primary hyperaldosteronism
Symptoms of Conn’s syndrome
Hypertension
Suppressed plasma-renin activity
Increased aldosterone secretion
What can cause Conn’s syndrome
Aldosterone producing adenoma
Bilateral adrenal hyperplasia
How is Conn’s syndrome diagnosed
- Aldosterone: renin ratio
- Saline suppression test
- CT of adrenal glands
- Adrenal venous sampling
Name 2 drugs that antagonise mineralcorticoid receptor
- Spironlactone
- Eplerenone
What are the effects of ACTH binding to the MCR2 receptor
- Increases cholesterol important into cell
- Increases cholesterol trafficking into mitochondria
- Increases adrenal blood flow
- ZF growth
Does mineralcorticoid receptor bind aldosterone or cortisol with higher affinity
They are bound with equal affinity
Symptoms of Liddle Syndrome
Hypertension
Hypokalaemia
Metabolic alkalosis
What hormones cause release of glucocorticoid
CRH from the hypothalamus causes ACTH release from ant. pituitary causing glucocortiod release from the adrenal
What causes increased release of CRH
Stress Ghrelin Catecholamine Ang 2 Immune response
What causes increased release of ACTH
Ang 2
IL-1, IL-6, IL-2
What inhibits release of CRH
Glucocorticoids ACTH CRIF ANP Opiods Oxytocin
How do glucocorticoids respond in the following conditions
a) starvation
b) infection
c) hypotension
a) Tissue breakdown for fuel
b) Immunosuppression
c) INcrease BP
What kind of receptor is melanocortic-2 receptor
7- transmembrane GPCR
What is melanocortin-2 receptors effect on camp
Activates cAMP mediated downstream pathways
Immediate effects mediated through activation of cAMP-dependent protein kinase A
What % of Cushing’s syndrome are hypertensive
80
Causes of Cushings syndrome (5)
- Iatrogenic
- Corticotroph adenoma of pituitary
- Bilateral adrenal hyperplasia
- Cortisol secreting adrenal adenoma
- Ectopic ACTH secreting neuroendocrine tumour
What imaging techniques can be used to diagnose/ track Cushings disease
MRI of the pituitary glands
CT of the adrenal glands
Inferior petrosal sinus sampling
How would you treat Cushings if it has a pituitary basis
Transphenoidal surgery
External beam radiotherapy
What drugs could you use to treat Cushings if it comes from an adrenal based problem
Metyrapone
Ketoconazole
Etomidate
What does it mean if there is high ACTH in petrosal veins compared to the pituitary in confirmed Cushings patient
Pituitary source of ACTH
What is Addisons disease
Primary adrenal failure
What are the possible causes of Addisons disease
AI
TB
What are the symptoms of early Addisons disease
Fatigue, weakness, malaise
Anorexia
Hyperpigmentation
What is an Addisonian crisis
‘failure to respond to stress’:
- low BP
- low glucose
- low sodium
- high potassium
How is Addisons disease diagnosed
Low 9am cortisol, but high ACTH
How is Addisons disease managed
Replacement steroids:
- Hydrocortisone, fludrocortisone
How would you treat an Addisonian crisis
IV fluid resus
IM hydrocortisone
What is secreted by the medulla of the adrenals
Catecholamines
What is the normal half life of catecholamines in circulation
10-100 seconds
What recovers catecholammines
Sympathetic nerves and chromaffin cells
What does COMT produce from
a) adrenaline
b) noradrenaline
a) Metadrenaline
b) Normetadrenaline
What are chromaffin cell tumours in the medulla known as
Phaeochromocytomass
What are chromaffin cell tumours in locations other than the medulla known as
Paragangliomas
Where are chromaffin cells found
- Adrenal medulla
- Para-aortic sympathetic chain
- Organ of Zuckerkandl
- Wall of urinary bladder
- Neck and mediastinal sympathetic chain
What is tyrosine converted to, and what is this then converted to
Dopamine
Noradrenaline
Where are alpha 1 adrenoreceptors found and what is the result of their activation
Veseels
Vascular and smooth muscle contraction
Where are alpha 2 adrenoreceptors found and what is the result of their activation
Presynaptic
Inhibitory to nora release- suppresses BP
Where are beta 1 receptors found and what is their action
Kidney- increased renin and lipolysis
Heart- positively inotropic and chronotropic
Where are beta 2 receptors found and what is their action
Lungs and blood vessels
Smooth muscle relaxation
Where are beta 3 adrenoreceptors found and what is their action
Brown fat tissue
Lipolysis energy expenditure
Where are D1 adrenoreceptors found and what is their action
Kidney, heart, cerebral vasculature dilation
What is the action of D2 adrenoreceptors
Presynaptic inhibition of noradrenaline
Prolactin release
Name some symptoms of catecholamine excess
Impending doom Diaphorsis Dyspnea Headache Hypertension Palpitation Tremor Nausea and vomiting Fatigue Orthostatic hypotension Hyperglycaemia Weight loss Epigastric/ chest pain Congestive heart failure
How would you diagnose catecholamine excess
24 hour urine metanephrines
Plasma metanephrines
CT/ MRI adrenals and abdomen
How would you treat catecholamine excess
Surgical resection
Pre-op alpha and beta blocker
How would you treat an acute crisis of catecholamine excess
IV Phentolamine or nicardipine
What drug should be avoided when treating catecholamine excess
Opiates
What would happen if you treated catecholamines with beta blockers alone
There would be unbalanced blockage b2 receptor so unopposed vasoconstriction