Adrenal Physiology Flashcards
What does the Yerkes-Dodson curve demonstrate?
The relationship between performance and stress levels
True or false: you have two different stress responses for physical vs psychological stressors?
False. You only have one generalized stress response
Describe general adaptation syndrome.
Nervous and hormonal responses resulting in a state of intense readiness with fuel mobilized for use
Where is the stress response coordinated?
Hypothalamus
Describe the short-term stress response. What occurs? What is the result (6)?
The hypothalamus directly stimulates the adrenal glands via the SNS, which causes catecholamines (Epi and NE) to be secreted from the adrenal medulla. Results in:
- Increased HR
- Increased BP
- Stimulates glycogenolysis and GNEO
- Dilation of bronchioles
- Decreased digestive system activity and urine output
- Increased metabolic rate
Describe the long-term stress response. What occurs?
CRH secreted from the hypothalamus to the anterior pituitary, which secretes ACTH into the blood to stimulate the adrenal cortex to secrete steroid hormones (MCCs & GCCs)
What are the effects of mineralocorticoids (MCCs) after being secreted from the adrenal cortex (2)? Example?
Retention of sodium and water by the kidneys
Increases blood volume and pressure
Ex: aldosterone
What are the effects of glucocorticoids (GCCs) after being secreted by the adrenal cortex (3)? Example?
- Proteins and fats converted to glucose or broken down directly for energy
- Increase blood glucose
- Suppression of the immune system
Ex: cortisol
Label the following aspects of the adrenal gland:
Adrenal medulla, Zona glomerulosa, Zona reticularis, Zona fasciculata.
What hormones are secreted by the four regions of the adrenal gland? (Zona golmerulosa, Zona fasciculata, Zona reticularis, Adrenal Medulla)
Zona golmerulosa: Mineralocorticoids
Zona fasciculata: Glucocorticoids
Zona reticularis: Androgens
Adrenal medulla: Stress hormones (Epi/NE)
Where in the cell are Epi and NE synthesized?
Cytosol of adrenal medulla cells
Approximately how much of the adrenal gland is composed of cortex vs medulla?
80-90% cortex
10-20% medulla
What types of hormones are synthesized by the adrenal cortex vs medulla?
Cortex: steroids
Medulla: amines
What is the embryonic origin of the adrenal cortex vs medulla?
Cortex: mesoderm
Medulla: neuroectoderm
What is the innervation of the adrenal cortex like compared to the medulla?
Cortex: Almost no innervation
Medulla: SNS innervation
How are products stored in the adrenal cortex vs medulla?
Cortex: lipid droplets
Medulla: amine granules
Are the adrenal cortex and medulla essential for life?
Cortex: essential
Medulla: nonessential
In the adrenal cortex, approximately how much cholesterol is taken up from the diet and how much is synthesized by the body?
Diet: ~80% from LDL
De novo synthesis: ~20%
If cholesterol is the starting material for all hormones of the adrenal gland, what determines what cholesterol is synthesized into?
Distribution of enzymes across the different cell types.
What enzyme catalyzes the conversion of cholesterol to pregnenolone? What stimulates this enzyme in the ZG, ZF, and ZR?
Desmolase
ZG: Ang II
ZF: ACTH
ZR: ACTH
What enzyme is absent in the ZG that prevents pregnenolone from being converted into GCCs or androgens?
17-α hydroxylase
What provides negative feedback to the hypothalamus and pituitary to stop the secretion of hormone by the adrenal glands?
Cortisol
ACTH is synthesized from what precursor? What else is it a precursor to?
Preproopiomelanocortin (POMC)
Also gives rise to α-melanocyte-stimulating hormone (MSH)
What does it mean for cortisol secretion to be pulsatile?
Alternating bursts of modest secretion separated by silent periods of little to no secretion; amount secreted per pulse does NOT vary
What does it mean for cortisol secretion to be diurnal? What structure regulates this?
Plasma ACTH and cortisol peak once a day prior to awakening
Regulated by the suprachiasmatic nucleus in the hypothalamus (circadian rhythm)
How is cortisol transported in the blood?
75% Corticosteroid-binding protein (CBP, transcortin)
15-20% albumin
5% unbound
How does the liver inactivate cortisol?
Conjugates with glucuronide or sulfate to increase cortisol solubility, which facilitates excretion by the kidneys.
What is the half-life of cortisol?
~70 minutes
Describe the mechanism of action of adrenal steroids after it reaches its target cell (4).
- Steroid diffuses through cell membrane and binds w/ intracellular receptor-HSP complex
- HSP released
- Activated receptor has a high affinity for steroid-response elements of DNA and binds to it
- Once bound, acts as transcription factor
Why can’t GCCs immediately relieve acute bronchial asthma attacks? What can they be used for though?
Since GCCs activate synthesis of proteins, there is a lag period of about 30 minutes for them to take effect. This is too slow for an asthma attack.
Can be used in the prevention of new asthma attacks
How long can the effects of GCCs last? Why?
Hours or days
Slow turnover of enzymes and proteins
What are the four main functions of cortisol?
- Stimulate GNEO in response to low blood sugar
- Increase protein and lipid breakdown
- Anti-inflammatory effects
- Suppress immune response
What enzymes of GNEO are stimulated by cortisol?
Phosphoenolpyruvate carboxykinase (PEPCK)
Glucose-6-phosphatase
If cortisol is supposed to increase glucose, why does it inhibit insulin-stimulated glucose uptake by muscles and adipose?
To preserve glucose for use by the brain (the brain can’t use muscle or fat)
Excess cortisol results in fat deposits where?
Face and trunk
What tissues are affected by cortisol?
All of them
Why can excess cortisol result in muscle weakness?
Cortisol breaks down muscle to increase blood glucose levels
What are the effects of cortisol on bones and its associated hormones?
Increase bone (calcium) reabsorption
Increases PTH secretion
Inhibits osteoblasts
What three separate conditions make up high-altitude illness? What medication can be used to treat it? How does it work?
- Acute mountain sickness
- High altitude cerebral edema
- High altitude pulmonary edema
Treated with dexamethasone (a GCC): reduces “leakiness” of cerebral and pulmonary blood vessels
What is the function of cortisol on the cardiovascular system?
Required for maintenance of normal blood pressure
Permits responsiveness of arterioles to the constrictive action of adrenergic and angiotensin stimulation
What effect does cortisol have on the kidneys?
Inhibits secretion and action of ADH (antagonist)
Increases GFR and RBF (which increases CO)
What effect does cortisol have on the CNS (specifically memory)?
Enhance memory consolidation
Impairs memory retrieval
What are the effects of cortisol on fetal development (3)?
Facilitates maturation in utero of the CNS, retina, skin, GI tract, and lungs
Increases surfactant synthesis (so breathing can occur immediately after birth
Maturation of digestive enzymes so the baby can digest milk
What is the difference between Cushing’s Syndrome and Cushing’s Disease?
Syndrome: broad term for hypersecretion of cortisol
Disease: Pituitary microadenoma that produces ACTH (does not respond to negative feedback)
____% of Cushing’s syndromes are ACTH dependent and _____% are ACTH independent.
~85% ACTH dependent
~15% ACTH independent
In regard to ACTH depending Cushing’s syndromes __% are caused by Cushing’s disease, __% by an ACTH secreting ectopic tumor, and _____ can occur but is rare.
80% Cushing’s disease
20% ACTH secreting ectopic tumor
Rare CRH secreting ectopic tumor
What are the potential causes of ACTH independent Cushing’s syndrome? (2)
Adrenal tumor
Iadogenic
What does it mean when Cushing’s syndrome is iatrogenic?
Results from treatment of rheumatoid arthritis, allergies, and prevention of transplant rejection
What are some of the symptoms of Cushing’s syndrome? (Combination of symptoms may vary).
*Truncal obesity
*Moon face
*Hypertension
Skin atrophy
Diabetes
Gonadal dysfunction
*Muscle weakness
*Increased body hair (hirsutism) and acne
Mood changes
Osteoporosis
If cortisol levels fluctuate throughout the day, how are adrenal diseases (like Cushing’s) diagnosed?
24-hour urine analysis
Normally <50mg/24hr
Why is DEX a good treatment for hypercortisolism?
DEX has a 25x greater affinity for cortisol’s receptors than cortisol itself
What is the difference between primary and secondary adrenal insufficiency?
Primary: Autoimmune destruction of adrenal cortex (Addison’s disease)
Secondary: Lack of ACTH
In Addison’s disease, what happens to cortisol, aldosterone, adrenal androgen, and ACTH levels?
ACTH increases
Cortisol, aldosterone, and adrenal androgen all decrease
What are some symptoms of Addison’s disease?
*Hyperpigmentation (especially in traumatized areas of the skin)
Weakness
Depression
Weight loss
Hypotension
In secondary adrenal insufficiency, what happens to cortisol, aldosterone, androgen, and ACTH levels?
Decreased ACTH and cortisol
No change to aldosterone and androgens
What are some symptoms of secondary adrenal insufficiency?
Similar to those of Addison’s disease WITHOUT hyperpigmentation
Mild orthostatic hypotension
Poor response to stress
What is cosyntropin? What is it used for?
Synthetic ACTH
Used in stimulation test for Addison’s disease; response means no disease
Any enzyme blockage that decreases cortisol synthesis will _____ ACTH and result in _____ _______?
Increase ACTH
Adrenal hyperplasia
