The adrenal glands Flashcards
What are the features of the Adrenal/Suprarenal Glands?
Adrenal/Suprarenal Glands;
- Paired glands situated superior to the kidneys
Comprised of two distinct tissues;
- Cortex - Glandular tissue derives from the mesoderm
- Medulla - Sympathetic nervous system derived from the neural crest (neuroectoderm)
Each region produces own set of hormones
What are the Regions of the Adrenal Gland?
Zona Glomerulosa;
- 15% cortex mass
- Secrete Aldosterone
Zona Fasciculata;
- 75% cortex mass
- Mainly secretes cortisol & corticosterone
Zona Reticularis;
- 10% cortex mass
- Mainly secretes dehydroepiandrosterone & androstenedione (weak androgens)
Medulla;
- Chromaffin cells secrete catecholamines (adrenaline + noradrenaline)
Name these layers of the Adrenal Gland?
See image
Fibrous capsule;
- Protective and fatty
Adrenal cortex;
- Arises from intermediate mesoderm
Adrenal Medulla;
- Chromaffin cells
- Darker as has granules containing adrenaline and noradrenaline
What are the features of the Adrenal Blood Supply ?
Adrenal Blood Supply;
- Blood via the superior, middle & inferior adrenal arteries - anastomose under the capsule
- Cortex = Short Cortical Arterioles - run parallel with cords of cells to the medulla
- Medulla = Long Cortical Arterioles - receives fresh arterial blood via long cortical arterioles, plus blood draining from the cortex (Contains adrenocoticoids which influence adrenalin production)
What hormones are produced in the adrenal cortex ?
Adrenal cortex produces hormones derived from cholesterol - corticosteroids;
Zona Glomerulosa;
- Mineralocorticoids - e.g Aldosterone (homeostasis of Na+ and K+ and water)
Zona Fasciculata;
- Glucocorticoids - e.g - Cortisol (energy metabolism and glucose availability)
Zona Reticularis;
- Gonadocorticoids - Sex steroids (weak androgens which are converted in tissue cells to more potent forms e.g Testosterone and Oestrogen)
How does the Adrenal Cortex synthesis Hormones?
Cortex takes up cholesterol and breaks it down into Pregnenolone which is the precursor for all hormones
Depending on which hormones and region of the cortex Pregnenolone is in depends on the hormone being made;
- Aldosterone in Zona Glomerulosa
- Cortisol in the Zona Fasciculata
- Androgens (Dehydroeplandreosterone) in the Zona Reticularis
These are lipids and aren’t soluble in plasma so need to be transported around the body one leaving the adrenal gland by transporter proteins (corticoglobular transporters or albumin)
80% of cortisol bound to transporter proteins to transport around body extending its half life to 60 - 90 mins
How do hormones work ?
Hormones act by binding to receptors
- Target cells present receptors
Receptors;
- Cell membrane receptors: Peptides, Glycoproteins and Catecholamines
- Intracellular receptors: Steroid and thyroid hormones
Cell membrane receptors;
- Catecholamines transported in plasma then binds to cell surface receptor target cell, initiate transduction and relay system of secondary messengers within the cell which will result ultimately In gene transcription . For globular proteins circulating in body, because of that shorter half life if no carrier protein `
Intracellular receptors;
- Cortisol is lipid soluble so can move through membrane and interact with receptors in cytoplasm and nucleus (longer half life cause binded to carrier protein, Active hormone is only active when dissociated from receptor) or in case of cortisol bind to its own receptor that helps transport it and either bind with its receptor in the cytoplasm or nucleus and become a transcription factor, up or downing gene regulation
Give a brief summary of the Long-term stress response?
Stress occurs and triggers the Hypothalamus to secrete releasing hormone into the anterior pituitary which triggers the release of ACTH from the anterior pituitary into the blood where it circulates the body and stimulates the Adrenal Cortex to produce Mineralocorticoids and Glucocorticoids.
Mineralocorticoids;
- Retention of sodium and water by kidneys
- Increased blood volume and blood pressure
Glucocorticoids;
- Proteins and fats broken down and converted to glucose, leading to increased blood glucose
- Immune system may be suppressed
What are the features of Cortisol ?
- Cortisol is a Glucocorticoid synthesised/released in response to physical and mental stress
- 95% of glucocorticoid activity results from secretion of cortisol (or hydrocortisone, same thing)
Clear diurnal rhythm of acitivity of cortisol;
- Peaks: 6-8am
- Lowest: Midnight - 2am
Main effects;
- Glucose mobilisation
- Maintain glucose availability
- Cardiovascular (blood volume)
- Sensitivity to catecholamines
What are the actions of Cortisol?
- Cortisol has immediate action on liver to enhance Gluconeogenesis to make glucose
- Cortisol prevents build up of fat and muscle protein, actively degrades muscle protein so liver can use its amino acids in glycogenesis, same in fats so glycerol in peripheral tissues can be used in liver for glucose production
Muscle cells;
- Cortisol inhibits protein synthesis. Muscle protein is broken down by proteolysis (stimulated by cortisol) to form amino acids which can be used in Gluconeogenesis
Fat cells;
- Cortisol inhibits lipogenesis. Fat is broken down by lipolysis (stimulated by cortisol) to form glycerol which can be used in Gluconeogenesis
Cortisol also decreases the cells susceptibility to insulin by down regulating GLUT receptors.
This mechanism has a major role in coping with physical (trauma, infection, allergies) & neurological (anxiety) stresses
Decrease in protein synthesis - increased neural excitability, lymph node lysis, inhibition of haematopoiesis/lymphocyte production - immunosuppressive, anti-inflammatory actions
What are the features of the Hypothalamic-Pituitary Adrenal Axis?
Hypothalamic-Pituitary Adrenal Axis;
- Regulatory feedback mechanism
- Stimulated by stress-physical (sympathetic system) or mental (limbic system)
- Corticotropin-releasing hormone targets anterior pituitary
- Adrenocorticotropic hormone release and targets zone fasiciculata
- Cortisol release - alleviates stress and levels feedback
What are the features of having Excess Glucocorticoid ?
Cushing’s syndrome;
Causes;
- ACTH-releasing pituitary tumour
- Abnormal function of hypothalamus - high levels CRH
- Ectopic ACTH-releasing tumour (usually in lungs/pancreas/kidney)
- Adrenal cortex tumour - hyper secretion of cortisol
- Clinical administration of glucocorticoid drugs
Clinical features;
- Moon rounding of face, loosing muscle mass and fat mass in extremities
- Skin weakness, more prone to splitting and damage
- Increase in hair loss and acne - due to androgenic affects of hormones
- Buffalo hump on back
- Hyperglycaemia - gluconeogensis & steroid diabetes
- Muscle wasting - proteolysis (muscle and bone)
- Increase in plasma free fatty acids - reduced lipogenesis/enhanced lipolysis
- Increased insulin release - redistribution of fat to trunk and face (B cell exhaustion)
- Tissue oedema, hypokalaemia, hypertension (Water and Na+ retention)
- GI tract ulceration - excess H+ secretion/decreased mucus production
- Decrease in protein synthesis - increased neural excitability, lymph node lysis, inhibition of haematopoiesis/lymphocyte production - immunosuppressive, anti-inflammatory actions
Treatment: Surgical tumour removal / decreased glucocorticoid drug use
What are the mechanisms that control aldosterone secretion?
There are 3 pathways that stimulate the Glomerulosa cells to synthesise Aldosterone;
- Renin-angiotensin cascade
- ACTH
- Increased plasma K+
Plasma K+;
Kidney responds to aldosterone released from the Adrenal Cortex, where it targets kidney tubular cells as its responding to angiotensin 2 levels, or increased potassium levels causing a loss of sodium and water out the urine. The kidney responds to aldosterone to start enhancing the uptake of sodium and excreting potassium to get back the homeostasis in blood.
RAAS;
The kidney also has baroreceptors which detect blood volume and dehydration and respond to this by secreting Renin which activates preprohormone Angiotensinogen which is secreted by the liver, converted into angiotensin 1 by angiotensin-covrting enzyme from epithelium of the lung, then into angiotensin-2 which works directly on the adrenal cortex to enhance the synthesis of aldosterone.
ACTH;
Angiotensin 2 also works directly on brain to increasing the CRH (corticotrophic releasing hormone) and AVP (Vasopressin and antidiuretic hormone to retain water) which stimulates the anterior pituitary to release ACTH. This will decrease sodium and water excretion and increase potassium excretion which will maintain blood volume and reducing hypotension.
What is the Action of Aldosterone ?
- In kidney tubular cells aldosterone binds the mineralocorticoid receptor - initiates gene expression
- Increased expression of apical epithelial Sodium channels - reabsorbs urinary Na+
- Increases activity if Na+/K+/ATPase
- Na+ reabsorbed along with H2O, K+ excreted in urine
- Blood volume & pressure increase
How can we Suppress Cortisol action inside Renal Tubular Cells?
11 B-HSD metabolises Cortisol into a product that has little affinity for Mineralocorticoids or Glucocorticoids receptors, therefore Aldosterone, which is not metabolised, will occupy Mineralocorticoids and Glucocorticoids receptors which will maintain the movement of potassium out of the body and sodium in.
Glycyrrhetinic acid inhibits 11 B-HSD. Therefore cortisol is not metabolised and perennially occupies Mineralocorticoids and Glucocorticoids receptors over aldosterone.
Some people have a defective 11 B-HSD enzyme and this prevents the breakdown of cortisol, causing it to bind over aldosterone, giving a hyperaldosteronism level and causing hypokalaemia and hypertension because bringing plenty sodium and water back into circulation.
Liquorice is high in Glycyrrhetinic acid and if a lot is consumed it can block 11 B-HSD, giving a hyperaldosterone level and causes hypokalaemia and hypertension because bringing plenty sodium and water back into circulation.
Give a brief summary of the Short-term stress response?
Short-term stress response;
- A nerve cell in the hypothalamus sends a signal to the spinal cord which relays it onto the adrenal medulla. It causes the adrenal medulla to produce Catecholamines like Epinephrine and Norepinephrine
Effects;
- Glycogen broken down into glucose; increased blood glucose
- Increased blood pressure
- Increased breathing rate
- Increased metabolic rate
- Change in blood-flow patterns, leading to increased alertness and decreased digestive and kidney activity
What are the features of Catecholamines ?
Catecholamines;
- Amino acid derivatives - modified from tyrosine
Neurotransmitters;
- Epinephrine
- Norepinephrine
- Dopamine
- Catecholamine synthesis occurs in Chromaffin cells
Key effects;
- Increases Heart Rate, BP and Respiratory Rate
- Diversion of blood to muscles
- Glucose mobilisation
Tyrosine derived from phenylalanine. Phenylketonuria is heel prick test in babies, issue in the enzyme that converted phenylalanine to tyrosine, essential for making neurotransmitters, lack in this causes developmental issues. Limit amount of phenylalanine in diet if don’t have this enzyme.
ACTH enhances synthesis catecholamines by enhancing enzymes converting tyrosine in to L-dopa which is then converted int dopamine. Also enhances effect of enzyme involved in converting dopamine into noradrenaline (20% of hormone in adrenal gland), and noradrenaline is modified by adding a methyl group to make adrenalin (80% of hormone within these chromaffin cells) and this stage is enhanced by cortisol.
Describe the process of Catecholamine Synthesis ?
Tyrosine is taken up into the chromaffin cell. Converted into L-Dopa which gets converted into dopamine. Dopamine is then transported into a granule within these chromaffin cells (via antiporter pumping in dopamine and hydrogen out). There is also a hydrogen pump pumping in hydrogen so we can maintain this gradient and keep pumping in dopamine.
Dopamine inside the granule is converted to noradrenaline which gets pumped back out into the cytoplasm of the chromaffin cell by an antiporter, and in the cytosol undergoes a last conversion from noradrenaline to adrenaline where cortisol is important in the enzyme activity responsible for this process.
Adrenaline will be pumped back inside the granule of the chromaffin cell (via hydrogen antiporter). In the granule the adrenaline and noradrenaline are combined in these chromatogranulins along with calcium and ATP ready and waiting on a sympathetic stimulus to depolarise these chromaffin cells and undergo exocytosis of this adrenaline and noradrenalin into systemic circulation for that immediate response. (these 2 hormones have the shortest half life, a few seconds until degraded) .
Give a summary of the Catecholamine Actions ?
a-Adrenergic Receptor Response (Noradrenalin - hormone sympathetic nerves);
- Decrease cAMP production
- Increase Ca++ (i)
- Contraction of smooth muscle (vascular, uterine, bladder)
- Relax intestinal smooth muscle
- Decrease insulin secretion in Pancreatic B cells
- Decrease parathyroid hormone in parathyroid gland
- Increase Renin secretion in Kidney Juxtaglomerular cells
B-Adrenergic Receptor Response (Adrenalin - Stress hormone of adrenal medulla);
- Increase cAMP production
- Decrease Ca++ (i)
- Relax smooth muscle (vascular, uterine, bladder)
- Relax Bronchial smooth muscle
- Relax intestinal smooth muscle
- Increase cardiac muscle contraction
- Increase Glycogenolysis in skeletal muscle/liver
- Increase Lipolysis in adipose tissue
- Increase Erythropoiesis in bone marrow
- Increase insulin secretion in Pancreatic B cells
- Increase parathyroid hormone in parathyroid gland
- Increase Renin secretion in Kidney Juxtaglomerular cells
Give a summary of the key Adrenocortical and Adrenomedullary hormones and their actions ?
See image
