Adrenal Glands Flashcards
Describe anatomical locaton of the adrenal glands.
Lie retroperitoneally on the upper pole of the kidneys.
State the embryological origin of the adrenal cortex, and medulla.
Adrenal Cortex
arises from intermediate mesoderm
Chromaffin cells (adrenal medulla) arise from neural crest cells (particularly, they are modified sympathetic ganglion cells)
Describe the anatomy of the adrenal gland.
In adults the adrenal cortex is composed of three zones—the zona glomerulosa, the zona fasciculata, and the zona reticularis.
Chromaffin cells establish the inner portion of the adrenal gland, which is called the adrenal medulla. The chromaffin cells of the adrenal medulla have the potential to develop into postganglionic sympathetic neurons.
The outer connective tissue capsule of the adrenal gland is penetrated by a rich arterial supply coming from three main arterial branches.
Identify the main hormones produced by each zone of the adrenal cortex.
PRODUCES STEROID HORMONES
1) Zona Glomerulosa
Mineralocorticoids – e.g. aldosterone
2) Zone fascilculata
Glucocorticoids – e.g. cortisol
3) Zona reticularis
Sex steroids – androgens
What factor controls aldosterone production by the zona glomerulosa ? What is the role of aldosterone ?
- Controlled by renin – angiotensin
- Role: electrolyte and fluid homeostasis
What factor controls cortisol production by the zona fasciculata ? What is the role of cortisol ?
- Secretion controlled by ACTH
- Role: carbohydrate, lipid and protein Metabolism
Describe blood supply of the adrenal cortex, and medulla.
- Supplied by the superior middle and inferior adrenal arteries; anastomose under the capsule
- Cortex receives short cortical arteries run in parallel with the cords of cells to the medulla
• Medulla receives:
- blood draining from the cortex (containing
adreno-corticosteroids which influence the
production of adrenaline by the medullary cells)
- Fresh arterial blood in long cortical arteries
Identify short-term stress response of the adrenal gland.
VIA CATECHOLAMINE (ADRENALINE AND NORADRENALINE) as a result of nervous stimulation of the adrenal medulla by the SNS, from the hypothalamus:
1) Increased HR
2) Increased BP
3) Liver converts glycogen to glucose and releases glucose to blood
4) Dilation of bronchioles
5) Changes of blood flow patterns leading to decreased digestive system activity and reduced urine output
6) Increased metabolic rate
Identify long-term stress response of the adrenal gland.
VIA MINERALOCORTICOIDS AND GLUCOCORTICOIDS as a result of hormonal stimulation (hypothalamus releases CRH which stimulates anterior pituitary corticotrophs to release ACTH which acts on adrenal cortex):
MINERALOCORTICOIDS
1) Retention of sodium and water by kidneys
2) Increased BV and BP
GLUCOCORTICOIDS
1) Proteins and fats converted to glucose or broken down for energy
2) Increased blood glucose
3) Suppression of immune system
Identify the main actions of cortisol on the body.
- It increases blood glucose by stimulating gluconeogenesis in the liver
- Stimulate breakdown of protein in muscle (via decreased protein synthesis using glucose in muscle cells, and increased proteolysis forming AAs which can then feed onto gluconeogensis in the liver)
- Stimulate breakdown of fat in fat cells (via decreased lipogenesis using glucose and instead increased lipolysis forming glycerol which can feed into gluconeogenesis)
-Therefore, increases plasma concentrations of glucose, FAs, AAs
+ Major role in ability to cope with physical (trauma, infection, allergies) or neurological (anxiety, restraint) stresses
+ anti-inflammatory/anti-allergic/anti-immune actions
Identify the main causes of Cushing’s disease.
- ACTH-releasing pituitary tumour
- Ectopic ACTH-releasing tumour (usually in lungs, pancreas or kidney)
- Tumour of the adrenal cortex - hyper-secretion of cortisol
- Administration of pharmacological doses of glucocorticoid drugs
All result in glucocorticoid excess
Identify the main clinical features of Cushing’s disease.
- Hyperglycaemia due to gluconeogenesis in liver- adrenal/steroid diabetes
- Muscle wasting (loss of protein synthesis in muscle and bone (and most tissues))
- Increase in FFA in plasma (reduced lipogenesis and enhanced lipolysis)
- Increased insulin release
- Tissue edema, hypokalemia, hypertension
- GI Tract ulceration
- Immunosuppressive, anti-allergic, and anti-inflammatory actions
Describe the physiological actions of increased insulin release, as part of Cushing’s Syndrome.
Redistribution of fat stores to face (moon face), neck, upper trunk
“buffalo hump”; β-cell exhaustion
Why does tissue edema, hypoK, hyperT occur as part of Cushing’s ?
Due to increased glomerular filtration (glucocorticoid effect) and water and Na+ retention (mineralocorticoid effects)
Why does GI tract ulceration occur as part of Cushing’s ?
Due to excess H+ secretion and decreased mucous production
alkalosis due to increased H+ loss in GI tract and kidney
Why do immunosuppressive and anti-allergic and anti-inflammatory actions occur as part of Cushing’s ?
Because decreases in protein synthesis results in increased neural excitability, lymph node lysis, inhibition of haematopoiesis and lymphocyte production
What is the treatment for Cushing’s ?
Surgical removal of tumour / decreases in drug dosage
Describe mechanisms controlling aldosterone secretion.
Three pathways stimulate glomerulusa cells to synthesize aldosterone:
1) Renin-angiotensin cascade
The liver synthesizes and secretes angiotensinogen. Renin, which is synthesized by the granular (or juxtaglomerular) cells of the juxtaglomerular apparatus (JGA) in the kidney cleaves this angiotensinogen to form ANG I. Finally, angiotensin-converting enzyme (ACE) cleaves ANG I to form ANG II. On the plasma membrane of the glomerulosa cell, ANG II binds to the AT1 receptor, which couples through the Gα q -mediated pathway to phospholipase C (PLC). Stimulation of PLC leads to the formation of (DAG) and IP3. DAG activates PKC. IP 3 triggers the release of Ca 2+ from intracellular stores, thus causing a rise in [Ca2+]i , which activates Ca 2+ -dependent enzymes such as PKC. These changes lead to depolarization of the glomerulosa cell’s plasma membrane, opening of voltage-activated Ca 2+ channels, and a sustained increase in Ca 2+ influx from the extracellular space. This rise in [Ca2+] i is primarily responsible for triggering the synthesis (i.e., secretion) of aldosterone. Aldosterone secretion increases because the rise in [Ca2+]i facilitates the production of pregnenolone either by directly increasing the activity of SCC or by enhancing the delivery of cholesterol to the SCC enzyme in the mitochondria. In addition, increased [Ca 2+ ]i also stimulates aldosterone synthase and in this manner enhances the conversion of corticosterone to aldosterone.
2) ACTH
Increases in ACTH raise [cAMP]i and activate PKA, which phosphorylates large numbers of cytosolic proteins. At some as-yet undefined level, these changes stimulate Ca 2+ influx across the plasma membrane and enhance the synthesis and secretion of aldosterone.
3) Increased plasma K+:
An increase in extracellular K + has a direct action on the glomerulosa cell. Several K + channels maintain the normal resting potential of these cells. Thus, high [K+]o depolarizes the plasma membrane and opens voltage-gated Ca2+ channels. The result is an influx of Ca2+ and a rise in [Ca2+]i that stimulates the same two steps as ANG II—production of pregnenolone from cholesterol and conversion of corticosterone to aldosterone. Unlike the situation for ANG II, the [Ca2+]i increase induced by high [K+]o does not require activation of PLC or release of Ca 2+ from the intracellular stores. Because increased [K+]o and ANG II both act by raising [Ca2+]i , they can act synergistically on glomerulosa cells.
Describe structure and cuntion of the juxta-glomerula apparatus.
The JGA is located at the glomerular pole of the nephron, between the afferent and efferent arterioles, where the early distal tubule comes in close proximity to its own glomerulus. Histologically, the JGA comprises specialized epithelial cells of the distal tubule called macula densa cells, as well as specialized smooth-muscle cells of the afferent arteriole, which are called granular cells or juxtaglomerular cells. Macula densa cells and granular cells communicate by means of an extracellular matrix.
Decreases in effective circulating volume—or the associated decreases in systemic arterial pressure—stimulate renin release from the granular cells of the JGA . Enhanced renin release leads to increased levels of ANG II and aldosterone. ANG II negatively feeds back on renin release directly by inhibiting renin release by granular cells (short-loop feedback). ANG II also negatively feeds back on renin release indirectly by acutely increasing systemic arterial pressure, thereby reducing the stimuli to release renin. Finally, aldosterone negatively feeds back on renin release more slowly by enhancing renal Na + reabsorption and thus increasing effective circulating blood volume and blood pressure. Therefore, ANG II and aldosterone complete the regulatory feedback circuit that governs the secretion of aldosterone.
Given as glucorticoids CAN bind to mineralocorticoid receptors (with same affinity as to its own receptor), why don’t they have mineralocorticoid affects ?
11 beat-hydroxysteroid dehydrogenase inside the cll metabolises cortisol to cortisone, a product that has little affinity for glucocorticoid or mineralocorticoid receptor into the cell.
HOWEVER,
Glycyrrhetinic acid inhibits 11 beta-HSD, so cortisol is not metabolised and preferentially occuppied MR and GR over aldosterone (and may then have mineralocorticoid effects)
SIMILARLY,
If disease where excess glucocorticoids (e.g. Cushing’s), then insufficient enzyme for all the glucocortioid, which then starts having effects.
Identify a disease related to glucorticoid/mineralocortioid deficiency.
Addison’s disease –
primary adrenal cor;cal insufficiency
Identify the main causes of Addison’s disease.
- Tuberculosis/ metastatic tumours (attacking/destroying cortex)
- Autoimmune adrenalitis - adrenal failure
- HIV - decreased immunity and increased viral and bacterial infections (that target the cortex)
- Atrophy due to prolonged steroid therapy
Describe clinical features of Addison’s disease.
1) Loss of weight/appetite, muscle weakness, nausea, vomiting
2) Low plasma glucose esp. after fasting (lack of glucocorticoid actions)
3) Low plasma Na+ (hyponatriemia) and high plasma K+ (hyperkalaemia) (due to lack of
mineralocorticoids)
4) Dehydration and hypotension due to 3. - systolic blood pressures 50-80 mmHg
5) Lethargy and dizziness on standing up due to 4
6) Severe cases present with skin pigmentation due to excess ACTH acting as MSH
Identify treatment options for Addison’s disease.
- Glucocorticoid replacement therapy – hydrocortisone administration morning (25mg) /afternoon (12.5 mg)
- Intravenous saline infusion if severely dehydrated and condition is life- threatening and administration of fludrocortisone (mineralocorticoid agonist)
