Physiology Exam 4 Lecture 13A [The Adrenal Glands: Miller]

The adrenal glands sit on top of the

kidneys

There are 2 adrenal glands (one on each kidney)

each have two layers:

Adrenal Cortex

Adrenal medulla

Adrenal cortex secretes

adrenocortical hormones

Adrenal medulla secretes

cathecholamines

The cortex is comprised of

- Zona glomerulosas: mineralocorticoids

- Zona fasciculata: Glucocorticoids > DHEA

- Zona reticularis: DHEA > glucocorticoids and androgen

Adrenocortical hormones are

steroid hormones (cholesterol backbone)

IMAGE of the Adrenal glands

The adrenal cortex consists of three layers and secretes

adrenocortical hormones (which are steroid hormones)

Mineralocorticoids (aldosterone) exclusively in the

Zona Glomerulosa

Glucocorticoids (Cortisol) Primarily in the

Zona Fasciculata

Sex steroid hormones (DHEA) primary adrenal source is the

Zona Reticularis

All steroid hormones are derived from

Cholesterol

The final steroid hormone produced depends on the

enzymes present in a given cell type

SUMMARY: The adrenal gland consists of two very different tissues

The cortex is a glandular tissue that secretes various steroids

The medulla is a nervous tissue that secretes catecholamines

SUMMARY: The adrenal cortex is comprised of 3 distinct layers

1. Zona glomerulosa is the top layer and exclusively secrets the mineralocorticoid aldosterone

2. Zona Fasciculata is the middle layer and primarily secretes the glucocorticoid cortisol

3. Zona Reticulata is the lowest layer and primarily secrets cortisol and the androgen DHEA

The rate limiting step for steroid hormone biosynthesis is the step that converts cholesterol into

pregneneolone

- this happens through an enzyme called P450-SCC

Steroid hormones are

lipophilic

Steroid hormones cannot be stored in

secretory vesicles

The rate of secretion of Steroid hormones is dictated by

the rate of synthesis

How are steroid hormones carried in the blood

extensively bound to plasma proteins

Steroid hormones bind to ________________ present in target cells - causing changes in transcription of genes. This is the primary mechanism of action of steroid hormones

intracellular receptors

SUMMARY: All steroids are derivatives of

cholesterol

SUMMARY: The conversion of cholesterol to pregnenolone is the rate limiting step of steroid synthesis and involves the actions of

P450-SCC

SUMMARY: From pregnenolone one can synthesize

cortisol, aldosterone, and DHEA

SUMMARY: The steroids are lipophilic and thus can

cross the plasma membrane

SUMMARY: because of their lipophilicity steroids cannot be stored but are

synthesized as needed

SUMMARY: Steroids are highly bound to ______ ______ _____ in the blood and interact with intracellular receptors to change gene expression

plasma protein carriers

The primary mineralcorticoid in humans is

aldosterone

The principal site of action of aldosterone is on the

distal and collecting tubules of the kidney, where it promotes Na retention and enhances K elimination during the formation of urine

Promotion of Na retention secondarily induces osmotic retention of water, thereby causing

expansion of the ECF volume, which is important in the long-term regulation of blood pressure

Mineralocorticoids are essential for

life

Without Mineralocorticoids ie aldosterone

a person rapidly dies from circulatory shock because of the marked fall in plasma volume

Aldosterone secretion is increased by

Activation of the renin-angiotensin-aldosterone system by factors related to a reduction in Na and a fall in blood pressure

Direct stimulation of the adrenal cortex by elevated plasma K concentrations

Aldosterone secretion is largely independent of

pituitary control by ACTH

- ACTH plays no role in Aldosterone secretion

The primary glucocorticoid in humans is

cortisol

The overall metabolic effects of cortisol are to

increase the concentration of blood glucose at the expense of protein and fat stores

How does cortisol increase concentration of blood glucose

Stimulates gluconeogenesis in the liver and inhibits glucose uptake by tissues other than the brain

- Increase plasma concentration of glucose

Stimulates protein degradation

- Increase plasma concentration of amino acids

Facilitates the breakdown of fat stores in certain adipose tissues

- Increase plasma fatty acids that can be used as an energy source instead of glucose

Other effects of cortisol

Important in lung development in the fetus

Necessary to permit catecholamines to induce vasoconstriction

- A person lacking in cortisol may go into circulatory shock in a stressful situation that demands immediate widespread vasoconstriction

Plays a key role in adaptation to stress (or perception of stress)

When stress is accompanied by tissue injury

inflammatory and immune responses accompany the stress response

Cortisol at physiological concentrations exerts modest _____ and _______ effects to help hold these immune system responses in check

inflammatory and immunosuppressive

At pharmacological concentrations glucocorticoids exert

stronger effects

synthetic glucocorticoids have been developed that maximize

anti-inflammatory and immunosuppressive effects while minimizing the metabolic effects

Examples of when glucocorticoids are given:

Rheumatoid arthritis, allergic disorders

Glucorticoids are used cautiously because

- A glucocorticoid- treated individual has diminished ability to resist infections

- Person can develop Cushing's syndrome

- Prolonged treatment can cause atrophy of the adrenal glands, preventing the body from producing its own cortisol

-Elevated glucocorticoids increase blood pressure

SUMMARY: The primary mineralocorticoid secreted by the adrenal cortex is

aldosterone

SUMMARY: aldosterone's primary target is the

distal convoluted tubule and the collecting ducts of the nephron to increase Na reabsorption and K secretion. Along with Na uptake this causes the additional H2O to be reabsorbed

SUMMARY: Aldosterone is crucial for

life

SUMMARY: Aldosterone secretion is stimulated by

plasma K levels and angiotensin II and is unaffected by levels of ACTH

SUMMARY: The primary glucocorticoid secreted by the adrenal cortex is

cortisol

SUMMARY: Cortisol has a variety of actions, many of which increase energy molecules in the plasma:

1. increase gluconeogenisis in the liver to release glucose

2. Increases protein breakdown to increase amino acid levels in blood

3. increases lipid breakdown to increase fatty acids in blood

4. Increases tissue sensitivity to catecholamines

5. Has slight anti-inflammatory properties at physiological concentrations

SUMMARY: Cortisol is a major

stress hormone

SUMMARY: synthetic glucocorticoids are used to

decrease inflammatory conditions like arthritis

SUMMARY: Synthetic glucorticoids must be used

sparingly and require careful use

Regulation of Cortisol Secretion (IMAGE)

In both sexes the adrenal cortex secretes small levels of ____ (female sex steroid hormone)

estrogens

In females the ovaries are the main site of

estrogen synthesis

Adrenal estrogens in males and females are not abundant enough to have

effects

In both sexes the adrenal cortex secretes small levels of _____ (Male sex steroid hormones)

androgens

Androgens

Primarily dehydroepiandrosterone (DHEA)

Most DHEA in sulfated form (DHEA-S)

DHEA/DHEA-S are weak androgens. They can be converted to the more potent androgen ______ in peripheral target tissues

testosterone

Main site of secretion of androgens in males are the

testes (testosterone)

Role of Adrenal DHEA in females

DHEA mediates androgen-dependent processes in females during puberty:

- Grotwth of pubic and axillary hair

- Enhancement of the pubertal growth spurt

- Development and maintenance of the female sex drive

Mediated by testosterone derived from the adrenal DHEA

The secretion of adrenal sex steroid hormones (DHEA/DHEA-S) is stimulated by

pituitary ACTH

The _______ are the primary sex steroid hormone producing cells

zona reticularis

Adrenal sex steroid hormones do not feed back on the hypothalamus and pituitary to suppress

CRH and ACTH

Adrenal sex steroid hormones negatively feed back on the hypothalamus and pituitary to suppress

GnRH, LH, and FSH secretion

If abnormally elevated levels of adrenal sex steroid hormones feedback on hypothalamus and pituitary would result in

suppression of gonadal function

SUMMARY: Cortisol release is controlled by

Stimulation from the release of CRH and ACTH

A negative feedback of cortisol to the hypothalamus (CRH release) and pituitary (ACTH release)

SUMMARY: The adrenal cortex can also release very small amounts of

estrogen and a higher lover of the androgen (DHEA) - weak androgen

SUMMARY: DHEA can be converted to

testosterone in target tissues

SUMMARY: In males the level of DHEA plays

almost no role as a much larger amount of testosterone is released by the testes

SUMMARY: In the female DHEA plays an important role in

1. development of pubertal hair

2. Enhances the pubertal growth spurt

3. Maintains sex drive

SUMMARY: The secretion of DHEA by the adrenal cortex is stimulated by

ACTH

SUMMARY: The DHEA produced by the adrenal cortex does not inhibit the release of

CRH and ACTH

Primary hyperaldosteronism - Conn's disease

hypersecreting tumor of aldosterone-secreting cells of the adrenal

Symptoms of Conn's disease

Hypernatremia (excessive Na retention)

Hypokalemia (excessive K depletion)

Hypertension (high blood pressure)

Cortisol Hypersecretion - Cushing's syndrome

Primary hypersecretion of cortisol

- Hypersecreting tumor of cortisol-secreting cells of the adrenal

Secondary hypersecretion of cortisol

- Excessive stimulation of the adrenal cortex by pituitary ACTH

ACTH-secreting tumors other than the pituitary (common in the lung)

Cushing syndrome is reflective of excessive ____________ - high blood glucose and protein shortage

gluconeogenesis

Cushings: Some of the extra glucose is deposited as body fat in locations characteristic of the disease --

abdomen, face, and above shoulder blades

Characteristics:

- moon face

- buffalo hump

- thin arms and legs

Cushings: Breakdown of body proteins leads to

muscle weakness and fatigue, thinning of the skin, tendency to bruise and poor wound healing, bone weakness

Cushings: Elevated cortisol increases blood pressure due to

the body becoming more sensitive to the effects of epinephrine and norepinephrine

Primary adrenocortical insufficiency or Addison's Disease

All layers of the adrenal cortex are severely under-secreting

DHEA, aldosterone, and cortisol are insufficient

Aldosterone insufficiency, if severe enough, can be fatal due to circulatory shock

Cortisol insufficiency, if severe enough, can be very serious and even fatal due to severe hypoglycemia

Addisons: From aldosterone hypo-secretion

Hyperkalemia

- Results in disturbances in cardiac rhythm

Hyponatremia

- results in hypotension

Life threating if severe enough

Addisons: From cortisol hypo-secretion

Hypoglycemia

Lack of permissive action for many metabolic activities

Poor response to physiological stress

Life-threatening if severe enough

Secondary adrenocortical insufficiency = decreased ACTH

Results in decreased cortisol (and DHEA) secretion

- Doesn't affect aldosterone secretion because it is not regulated by ACTH

Cortisol hypo-secretion

- Hypoglycemia

- Lack of permissive action for many metabolic activities

- Poor response to physiological stress

- Life-threatening if severe enough

SUMMARY: Primary hyperaldosteronism is caused by a

hyper-aldosterone secreting tumor of the adrenal cortex (Conn's syndrome).

SUMMARY: Conn's syndrome leads to

Hypernatremia

Hypokalemia

Excessive water retention leading to hypertension

SUMMARY: Primary hypersecretion of cortisol is usually due to

a tumor of the cortex (Cushing's syndrome).

SUMMARY: Secondary hypersecretion of cortisol is usually due to

over stimulation of the adrenal cortex by ACTH which can arise from the piruitary or certain lung cancers

SUMMARY: Hypersecretion of cortisol cause

Hyperglycemia

Deposition of fat in face, abdomen, and upper back

Hypertension

Muscle wasting and fatigue

frequent infections

SUMMARY: Primary adrenocorticoid insufficiency is usually due to an

autoimmune disease where the adrenal cortex layers are attacked (Addison's Disease)

SUMMARY: Low levels of aldosterone and cortisol can be life threatening while decreased DHEA only has effects in

women

SUMMARY: Addison's disease leads to

Hyperkalemia

Hyponatremia

Hypovolemia

Hypoglycemia

decreased responses to sympathetic activation

usually severe enough to require treatment or death can occur

SUMMARY: Secondary adrenocorticoid insufficiency usually cuased by

insufficient release of ACTH

SUMMARY: Unlike Addison's Disease, in Secondary adrenocorticoid insufficiency, aldosterone secretion is

unaffected and only cortisol and DHEA are low

The innermost region of the adrenal is the

Adrenal medulla

The adrenal medulla is a modified part of the sympathetic nervous system because

Releases chemical transmitters directly into the circulation upon stimulation by the preganglionic fiber

Like sympathetic neurons, releases norepinephrine

Most secreted hormone by the adrenal medulla is epinephrine

Most secreted hormone by the adrenal medulla is

epinephrine

Epinephrine and norepinephrine are

catecholamines

Catecholamines are synthesized in

adrenomedullary secretory cells