Learning Outcomes
- List the main hormones produced by the adrenal gland and their functions
- Describe the circadian rhythm of cortisol and its control by CRH and ACTH
- List the main actions of glucocorticoids like cortisol
- Explain the significance of cortisol during major physical stress
- Compare and contrast control of aldosterone secretion with that of cortisol
- Describe the mineralocorticoid effects of aldosterone in terms of its renal actions
- Describe the main effects of glucocorticoid deficiency and excess and explain these in terms of normal hormonal actions
- Explain how ACTH levels will change with different types of cortisol abnormality
- Describe the effects of excess or deficient aldosterone in terms of these actions
What secretes corticosteroids?
The adrenal cortex
Name the layers of the Adrenal Cortex
- Zona Glomerulosa
- Zona Fasiculata
- Zona Reticularis
What do the following secrete?
- Zona Glomerulosa
- Zona Fasiculata
- Zona Reticularis
- Mineralocorticoids
- Glucocorticoids
- Adrenal Androgens
How are the following transported in the blood?
- Cortisol
- Aldosterone
- Adrenal Androgens
-
98% bound primarily to corticosteroid-binding globulin (trancortin)
-
60% bound primarily to albumin
-
98% bound exclusively albumin
98% bound primarily to corticosteroid-binding globulin (trancortin)
60% bound primarily to albumin
98% bound exclusively albumin
Where are the following secreted from?
- Catecholamines
- Androgens
- Cortisol
- Aldosterone
- Medulla
- Zona Reticularis (Adrenal Androgens)
- Zona Fasiculata (Glucocorticoids)
- Zona Glomerulosa (Mineralocorticoids)
(some overlap between fas and ret layers in terms of release)
Intracellular actions of adrenal steroids
Steroid hormones enter cytoplasm, bind to cytoplasmic receptors, create a Hormone-Receptor complex, enter the nucleus and cause a change in gene activity, altering protein syntesis, giving alterations in structural proteins or enzyme activity and resulting in a target cell response.
Glucocorticoids: Regulation of Cortisol Secretion
How is cortisol secretion regulated?
Stress (Physical, Emothional, Chemical, Others)
Circadian or Diurnal Rhythm
Outline the actions of Glucocorticoids
- Muscle
- Liver
- Fat Cells
- Immune System and Inflammation
- Net loss of amino acids (glucose)
- Gluconeogenesis (glucose) and glycogenesis
- Free fatty acids mobilisation - lipolysis
- Suppressed
Generally catabolic, but in the liver, glycogenesis occurs.
Cortisol has a role in adaptation to stress
Cortisol directly promotes rapid supply of glucose to tissues
Cortisol is a ’permissive’ hormone
Give two important actions of Cortisol
-
it effects the other counter-regulatory hormones (see picture) eg. Insulin, glucagon, adrenaline, growth hormone
-
Cortisol is required for the expression of adrenergic & angiotensin II receptors in the CVS - needs to be present for blood pressure to be normal
Give some causes of Glucocorticoid Excess
- Hypothalamic tumour
- Anterior pituitary tumour (Cushing’s Disease)
- Adrenal tumour
- Ectopic tumor
What syndrome is caused by Glucocorticoid Excess?
Cushing's Syndrome
- What can secondary hypersecretion of glucocorticoids be caused by?
- What can primary hypersecretion of glucocorticoids be caused by?
- a hypothalamic problem or pituitary problem
- problem with the adrenal cortex
What are the following characterised by?
- 2ry hypersecretion of glucocorticoids due to a hypothalamic problem?
- 2ry hypersecretion of glucocorticoids due to a pituitary problem?
- 1ry hypersecretion of glucocorticoids due to a problem with the adrenal cortex
- Which of these is Cushing's Syndrome?
- High CRH, ACTH and Cortisol Levels
- High ACTH and Cortisol Levels, Low CRH Levels
- High Cortisol Levels, Low CRH and ACTH Levels
- 2. Ant Pituitary Tumour (High ACTH and Cortisol Levels, Low CRH Levels)
Cushing's Syndrome
Give examples of signs and symptoms
(generally)
Abdominal Striae
Central Fat Deposition
Thinning of Limbs
Bruising
Moon face
Buffalo Hump
Cushing's Syndrome
What do the effects on the following give rise to
- Carbohydrate Metabolism
- Protein Metabolism
- What other effects are there?
-
Hyperglycaemia - increase blood glucose levels x 2 normal “Adrenal diabetes”
-
Protein shortage - muscle weakness
Stretch lines, (Striae)
Easy bruising
Thinning of Skin
-
Suppression of the immune system and Osteoporosis
Hyperglycaemia - increase blood glucose levels x 2 normal “Adrenal diabetes”
Protein shortage - muscle weakness
Stretch lines, (Striae)
Easy bruising
Thinning of Skin
Suppression of the immune system and Osteoporosis
Give the symptoms of Cushing's Syndrome
(with the mneumonic CUSHING)
C - Central obesity, collagen fibre weakness, comedones (acne)
U - Urinary free cortisol and glucose increase
S - Striae, Suppressed Immunty
H - Hypercortisolism, Hypertension, Hyperglycaemia, Hypercholesterolemia
I - Iatrogenic (increased administration of corticosteroids)
N - Noniatrogenic (neoplasms)
G - Glucose intolerance, Growth Retardation
Mineralocorticoids: regulation of aldosterone secretion
Actions of aldosterone (mineralocorticoid effect)
What are the actions of aldosterone?
- increased Na+/H2O absorption
- increased K+/H+ secretion
- increased blood volume/BP
Increased production of ion channels
Increase in production of na/k ATPase
This means that there is increase sodium absorption and K+ secretion
What does Aldosterone Deficiency lead to?
-
increased loss of Na+ and H2O in the urine - dehydration, plasma depletion and hypotension
-
renal retention of K+ and hyperkalaemia. Increases cardiac excitability and can cause ventricular fibrillation
- renal retention of H+ producing a metabolic acidosis
What is Primary Hyperaldosteronism?
Conn's Syndrome
Secreting Tumour
Increased Aldosterone
Increased Na+ retention, increased total body Na+, increased ECF
Increased BP - Plasma volume expansion
Decreased Renin
Increased K+ loss
Decreased plasma K+
(secreting tumour)
What is secondary hyperldosteronism caused by?
Overactivity of the Renin-Angiotensin System
What are the clinical manifestations of primary hyperaldosteronism?
Hypertension
Hyperkalaemia
Hypervolaemia (without peripheral oedema)
Metabolic Alkalosis
What is renal insufficency usually due to?
a problem in the RAAS
