9 - Adrenal Hormones Flashcards
What are the 3 stress response pathways regarding adrenal hormones?
1 - Humoral pathway (cortisol)
2 - Neuronal pathway (epinephrine/norepinephrine)
3 - Renin-angiotensin pathway (aldosterone)
Describe the brief anatomy of the adrenal gland
- Cortex (outer layer)
- Medulla (inner layer)
- Chromaffin cells are found on the inside
- Both circulation and postganglionic axons gain access to medulla and reach the chromaffin cells
- Cholesterol is used to make steroid hormones in the adrenals (testosterone, etc)
- Chromaffin cells are innervated and signaled to produce steroid hormones via axons then the steroid hormones are sent out to the circulation
Which of the three stress response pathways is fast? Which ones are slow?
Cortisol = slow Epi/NE = fast Aldosterone = fast
How is the release of cortisol regulated?
Cortisol regulates its own release ***
Describe the steps in the release of cortisol
- Stress is the “trigger”
- Affects the visceral brain then the limbic system then the hypothalamus
- The hypothalamus releases CRH (corticotropic releasing hormone)
- CRH acts on the anterior pituitary
- The anterior pituitary then releases ACTH (adenocorticotropic hormone)
- ACTH acts on the adrenal cortex
- The adrenal cortex then releases cortisol
How does the body know when to stop making cortisol?
When cortisol is high, the body has negative feedback on the limbic system, hypothalamus and anterior pituitary to shut it down
Can the body store cortisol?
NO
- Cortisol is a lipid that is derived from cholesterol
- This means that it can easily move across lipid bilayers
- It can therefore not be stored or contained
What effect does this have on the response time of cortisol?
Since cortisol can’t be stored, it needs to be synthesized when needed
This means that the response time is slow
What is 17-alpha hydroxylase?
An enzyme that is involved in the synthesis of both cortisol and aldosterone
It is clinically relevant because a deficiency of 17-alpha hydroxylase leads to problems
What are cortisol and aldosterone derived from? What does this mean for 17-alpha hydroxylase?
Cortisol and aldosterone are both derived from cholesterol. This means that 17-alpha hydroxylase is involved in the process of converting cholesterol into cortisol and aldosterone
What is the clinical significance of cortisol and aldosterone both being derived from cholesterol and following a lot of the same pathway to production?
If there is an enzyme deficiency in the pathway from cholesterol to cortisol, more cholesterol will be pushed into the aldosterone pathway
Same for aldosterone –> More cortisol will be produced
What process of the synthesis of cortisol takes the most time?
Translation
What are glucocorticoids?
Glucocorticoids (GCs) are a class of steroid hormones which bind to the glucocorticoid receptor that is present in almost every vertebrate animal cell.
GCs are part of the feedback mechanism in the immune system that turns immune activity (inflammation) down. They are therefore used in medicine to treat diseases caused by an overactive immune system.
How do steroidal anti-itch or anti-inflammatory creams work?
Steroid creams suppress the inflammatory process for a while
- When a glucocorticoid binds to a receptor, there is negative feedback which decreases the levels of precursors for prostaglandin
Describe how these creams work
If there is cortisol around, there are no prostaglandins, and therefore you are not producing inflammation
This is a slow pathway because cortisol synthesis is slow
Describe the action of glucocorticoids
Glucocorticoids…
- Influence carbohydrate metabolism
- Act on muscle, adipose tissue, liver, intestine and kidney
What is the goal of glucocorticoids?
Conservation of glucose
How do glucocorticoids conserve glucose?
- Stimulate protein catabolism and gluconeogenesis (stored liver glycogen –> free blood glucose)
- Inhibit glucose uptake by adipose tissue
How are steroid hormones degraded?
Nothing related to cholesterol can be degraded
Cholesterol takes a lot of energy to make, so this is actually a “bad investment” because when you’re done using it you can’t get the energy back, you just have to secrete it out
Describe the process of secreting steroid hormones
- In order to secrete the hormone, you first need to inactivate the hormone
- Next, you need to make it water soluble enough to leave in the urine
What organ makes the cholesterol more soluble?
Liver
How does the liver make cholesterol more soluble?
Glucuronidation
- Conjugation of cholesterol to increase solubility
- Uses glucoronic acid
What are two clinical disorders that result from irregularities in cortisol hormone levels?
- Cushing’s disease (high cortisol)
- Addison’s disease (low cortisol)
Describe the hormone levels in Cushing’s disease
High glucocorticoids
High mineralocorticoids
Caused by high ACTH
Describe the hormone levels in Addison’s disease
Low glucocorticoids
Low mineralocorticoids
High ACTH and MSH* (loss of feedback)
Describe the other effects of Cushing’s disease
Protein problems
- Thinning of skin
- Loss of bone
- Poor wound healing
- Muscle wasting
- Capillary fragility
- Impaired growth
Carbohydrate problems
- Abnormal glucose tolerance
- Overt diabetes mellitus
Lipid problems
- Centripetal fat distribution
- Moon face
Electrolyte problems
- Sodium retention
- Potassium loss
- Hypertension
General effects
- Hematopoietic effects: loss of blood cells
- Impaired immune function
Describe the other effects of Addison’s disease
- Hypoglycemia
- Sodium loss
- Potassium retention
- Hypotension
- Pigmentation of the skin
Case study - symptoms for Addison’s disease
A 15-year old was seen by a tertiary care provider for multiple symptoms:
- Unexplained weight loss
- Fatigue
- Thirst and craving for salty foods
- Hypotension
- Hyperpigmentation (spots under tongue)
How would you test for Addison’s disease?
- Initial cortisol levels were very low
- So, they gave a “test” of ACTH to see if it stimulated the production of cortisol
- The cortisol level did not really increase, so the ACTH is not the problem
- There is a problem in the body with ACTH leading to cortisol production
- Diagnosis of Addison’s disease was made
Describe the Renin-Angiotensin System
- Stress acts on the visceral brain
- The visceral brain secretes norepinephrine
- The norepinephrin acts on the kidneys (maculla densa)
- The maculla densa of the kidney releases Renin
- Renin cleaves serum-glycoprotein into Angiotensin
- Angiotensin acts on the adrenal cortex to secrete Aldosterone
What are mineralcorticoids?
Mineralocorticoid(s) are a class of steroid hormones characterized by their influence on salt and water balances. The primary mineralocorticoid is aldosterone.
What are the actions of mineralcorticoids?
Mineralcorticoids regulate the retention and excretion of minerals, especially sodium
Where does aldosterone act? What is its target?
Kidney and large intestine
What effects does aldosterone have on the kidney and large intestine?
Retention of sodium
- Stimulate the uptake of sodium in the collecting duct of the kidney
- Stimulate uptake of sodium in the large intestine
- Retention of water to contribute to increase blood pressure
What is the neuronal pathway?
The autonomic nervous system activation pathway
Describe the steps in the neuronal pathway
- Stress acts on the visceral brain
- The neurohypothalamus is activated
- This activates the autonomic nervous system
- The ANS activates acetylcholine neurotransmitter
- The ACh acts on medulla chromaffin cells
- Chromaffin cells of the adrenal gland secrete epinephrine and norepinephrine
Describe the synthesis of catecholamines
Tyrosine --> L-DOPA --> L-Dopamine --> Norepinephrine --> Epinephrine
What type of receptors do norepinephrine and epinephrine act on?
Adrenergic receptors
What are the two types of adrenergic receptors?
- Alpha adrenergic receptors
- Beta arenergic receptors
What happens when alpha adrenergic receptors are stimulated?
Elevation in Ca++
What happens when beta adrenergic receptors are stimulated?
Elevation in cAMP
What does epinephrine do in the liver?
In liver cells, epinephrine allows glycogen –> glucose –> raise blood sugar *** (gluconeogenesis)
In your fight/flight reaction, you can expect an increase in blood sugar
What are the actions of epinephrine?
- Epinephrine regulates carbbohydrate metabolism, but also heart output and other functions
- Acts on muscle, liver, adipose tissue, heart and other organs
- Aims to prepare the body for a fight or flight reaction
In which ways does epinephrine prepare the body for a fight or flight reaction?
- Stimulates energy generation (glycogen and glucose breakdown)
- Elevates heart contraction force
What is the effect of epinephrine on the muscle?
Stimulates glycolysis and glycogen breakdown (NOT gluconeogenesis)
What is the effect of epinephrine on the heart?
Increases contraction force
What is the effect of epinephrine on the salivary glands?
Stimulates amylase secretion
What is the effect of epinephrine on the adipose tissue?
Stimulates breakdown of storage fat
What is the effect of epinephrine on the liver?
Stimulates glycogen breakdown and gluconeogenesis
Give a summary of the humoral pathway of stress response
Cortisol
- Cortisol is synthesized and secreted
- Cortisol binds to glucocorticoid receptors
- The two effects are (1) an anti-inflammatory response and (2) storage of energy fuels
Give a summary of the renin-angiotensin pathway of stress response
Aldosterone
- Aldosterone is synthesized and secreted
- Increases sodium uptake
- Causes a retention of water and an elevation in blood pressure
Give a summary of the neuronal pathway of stress response
Epinephrine/Norepinephrine
- Epi/Norepi are synthesized and secreted
- They act on the target cell receptor
- This causes a rapid conversion of energy fuels to glucose
