9 - Adrenal Hormones Flashcards by Andrea Okas

What are the 3 stress response pathways regarding adrenal hormones?

1 - Humoral pathway (cortisol)
2 - Neuronal pathway (epinephrine/norepinephrine)
3 - Renin-angiotensin pathway (aldosterone)

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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

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Which of the three stress response pathways is fast? Which ones are slow?

Cortisol = slow
Epi/NE = fast
Aldosterone = fast

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How is the release of cortisol regulated?

Cortisol regulates its own release ***

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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

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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

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Can the body store cortisol?

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

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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

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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

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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

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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

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What process of the synthesis of cortisol takes the most time?

Translation

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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.

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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

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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

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Describe the action of glucocorticoids

Glucocorticoids…

Influence carbohydrate metabolism
Act on muscle, adipose tissue, liver, intestine and kidney

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What is the goal of glucocorticoids?

Conservation of glucose

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How do glucocorticoids conserve glucose?

Stimulate protein catabolism and gluconeogenesis (stored liver glycogen –> free blood glucose)
Inhibit glucose uptake by adipose tissue

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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

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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

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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