Exam 1 -- Pt 5: Adrenals Flashcards
What is another name for the adrenal glands?
suprarenal glands (=”above the kidney”)
T/F. The adrenal glands hormones are not required for maintenance of life.
FALSE– They ARE REQUIRED for maintenance of life!!!!
What are the two “parts” of the adrenal gland? Where are they derived from and what hormone types do they secrete?
- outer Cortex–> mesodermal orgin; secrete steroids
2. inner Medulla–> chromaffin cells from ectodermal cells of neural crest; secrete catacholamines (Epi, NE)
What are the layers from outside in of the adrenal gland? (4)
- Zona glomerulosa
- Zona fasciculata
- Zona reticularis
- Adrenal medulla
(1-3 = adrenal cortex)
What hormones are released from:
- Zona glomerulosa
- Zona fasciculata
- Zona reticularis
- Adrenal medulla
- Mineralcorticoids (Ex: adlosterone)
- Glucocorticoids (Ex: cortisol, corticosterone, cortisone)
- Androgens (Ex: DHEA)
- Stress hormones (Epi and NE)
Where are the adrenal glands located?
in the retroperitoneal cavity on top of each kidney
What percentage of secretion does the Medulla have for the adrenals? What does it secrete?
(ectoderm derived)
20%
Secretes catacholamines (Epi and NE)
What percentage of secretion does the Cortex have for the adrenals? What does it secrete?
(mesoderm derived)
80%
Secreted Steroid hormones:
1. Mineralocorticoids (zona glomerulosa)
2. Glucocorticoids (primarily zona fasciculata)
3. Andorgens (primarily zona reticularis)
What is the mineralocorticoid that the adrenal cortex secretes?
aldosterone
What do mineralocorticoids have control over?
sodium and potassium
What stimulates the release of aldosterone from the adrenal cortex?*
angiotension II
What controls the secretion of mineralocorticoids?
mainly by renin-angiotensin system (kidney) via angiotension II, which stimulates aldosterone synthase
When would the renin-angiotension-aldosterone system kick in?
when blood pressure falls and kidney filtration levels drop, renin-angiotensin will assist increase of glomerular filtration
What affect does angiotensin II have on blood vessels?
causes them to constrict
What is the function of aldosterone?
increases reabsorption of Na and water; therefore increasing blood pressure and fluid volume
What organs are involved in the Renin-Angiotensin-Aldosterone System?–How?
- Kindey–> produces renin, which activates…
- Liver–> tp convert angiotensinogen to Angiotensin I, then…
- Lungs–> converts it to Angiotensin II with ACE
- Adrenal –> releases aldosterone due to stimulation by Angiotensin II
What are the glucocorticoids secreted by the adrenal cortex?
cortisol, corticosterone, cortisone
What do glucocorticoids affect?
- metabolism of glucose, proteins, and fat
- has anit-inflammatory activity*
What is the secretion of glucocorticoids controlled by?
ACTH (adrenal corticotropic hormone)–from anterior pituitary
What are two drugs that inhibit glucocorticoids?
- Metyrapone
2. Ketoconazole
What is Metyrapone do?
inhibits 11beta-hydroxylase; prevents production of corticosterone and cortisol
What is ketoconazole used for?
to treat fungal infections
inhibits several steps, including cholesterol desmolase (step from cholesterol–> pregnenolone)
How common is Adrenal Insufficiency (AI)? How serious is it?
rare; and potentially life-threatening
What is a type of Androgen released by the Adrenal cortex?
Dehydroepiandrosterone (DHEA)
What controls the secretion of Androgens from the adrenal cortex?
ACTH (adrenal corticotropic hormone) from and anterior pituitary
(also controls glucocorticoids secretion too)
Androgens have similar functions to what other structure?
testes
What involves masculinization in females, suppression of gonadal fxn in both sexes, early development of pubic/axillary hair, and increase levels for 17-ketosteroids?
Adrenogenital syndrome
What is increased in Adrenogenital syndrome?
increased synthesis of adrenal androgens–> high levels of DHEA and androstenedione
What would cause Adrenogenital syndrome to develop?
a deficiency of 21-beta hydroxylase
- which increases androgen production and
- decreases mineralcorticoid and glucocorticoid production
What hormone do the adrenals produce the most of on an average day?
Cortisol at 20 mg/day
(Androgens 10-15 mg/day
Corticosterone 2 mg/day
Aldosterone .15 mg/day)
T/F. The Adrenal cortex and medulla often behave as a functional unit.
True
Which is fast acting, the medullary hormones or the cortical hormones?
medullary hormones are fast acting; the cortical hormones are slower acting
What are three things that the slower acting cortical hormones serve as?
- maintain or increase sensitivity to medullary hormones
- maintain or enhance capacity of tissue to respond to medullary homrones
- act as modulators rather than initiators of responses
What are the two hormones released by the adrenal medulla?
Epinephrine and Norepinephrine
Which medullary hormone increases blood sugar levels, increases HR, increases contractility of heart, and relaxation of smooth muscles in airway?
Epinephrine
What medullary hormone increases narrowing of blood vessels, low blood pressure, and may induce septic shock?
Norepinephrine
What medullary hormone stimulates the liver to do catabolism of glycogen to glucose?
epinephrine
What is the “emergency hormone” for fight or flight?
epinephrine
T/F. Th e only adrenal medullary hormone NE increases levels of free fatty acids.
False- BOTH Epi and NE increase levels of free fatty acids
What is the precursor for all adrenocortical steroids?
cholesterol
What is deficient with a 17-alpha hydroxylase deficiency?
- aldosterone
- cortisol
- DHEA and Androstenedione
What is deficient with a 17,20 lyase deficiency?
- DHEA and Androstenedione
What is deficient with a 3-beta Hydroxysteroid dehydrogenase deficiency?
- Aldosterone
- Cortisol
- Androstenedione
What is deficient with a 21-beta Hydroxylase deficiency?
- Aldosterone
- Cortisol
What is deficient with a 11-beta Hydroxylase deficiency?
- Aldosterone
- Cortisol
What is deficient with an Aldosterone synthase deficiency?
- Aldosterone
How does cholesterol circulate?
bound to LDL
Where are receptors located for LDLs?
in membranes of adrenocortical cells; take up by endocytosis and esterfied and stored in cytoplasmic vesicles until needed for synthesis of steroid hormones
What adrenal hormones have anti-inflammatory effects?
glucocorticoids
What adrenal hormone stimulates gluconeogenesis and storage of glycogen?
glucocorticoids
What are glucocorticoids affect on the immune system?
suppresses the immune response, can suppress the thymus
What impact do glucocorticoids have on the glomerular filtration rate (GFR)?
increases it
- causes vasodilation of the afferent arterioles
- increases renal blood flow and GFR
What does cortisol (type of glucocorticoid) have a metabolism impact on? What does this increase synthesis of?
protein, fat, CHO in order to increase glucose synthesis
What hormones are essential for survival during fasting? Why?*
Glucocorticoids, b/c they simulate gluconeogenesis
What are three actions of cortisol that help with its anti-inflammatory effect?
- induces synthesis of lipocortin
- Inhibits production of interleukin-2 and the proliferation of T lymphocytes
- Inhibits release of histamine and serotonin from mast cells and platelets
We know glucocorticoids inhibit the production of interleukin-2 and proliferation of T lymphocytes, how can this be used medically?
exogenous glucocorticoids used to prevent rejection of transplanted organs
Why is the stimulate of synthesis of lipocortin by glucocorticoids have an anti-inflammatory effect?
- lipocortin is an inhibitor of enzyme phospholipase A2
(- Phospholipase A2 liberates archidonic acid from membrane phospholipids and provides precursor for prostaglandins and leukotrienes that mediate the inflammatory response)
What ways can glucocoirticoids prevent hypoglycemia?
- decrease utilization of glucose by muscle and adipose tissue
- decrease responsiveness of these tissues to insulin
What will decrease utilization of glucose coupled with increase gluconeogenesis lead to?
increase glycogen storage in liver and muscle
When it comes to vascular physiological functions, what role to glucocorticoids have?
necessary for maintenance of normal blood pressure by up-regulating alpha-1 adrenergic receptors**
- which is required for vasoconstriction response of arterioles to the SNS and circulating catacholamines
For vascular physiological functions, hat will decrease in cortisol cause? What about increase in cortisol?
decrease cortisol –> hypotension
increase cortisol –> hypertension
What impact do glucocorticoids have on bone formation?
inhibits bone formation
- decreases osteoblast formation
- decreases intestinal Ca++ absorption and therefore decreases synthesis of type I collagen
(may increase risk of osteoporosis risk)
What effects do glucocorticoids have on the CNS, specifically the brain?
glucocorticoid receptors are found in the brain, especially in the limbic system (emotion, motivation, drive)
What effects do glucocorticoids have on sleep? When is the largest burst of ACTH and cortisol occur?*
- decreases REM sleep
- increases slow wave sleep
- increases awake time/wakefulness
largest burst occurs just before awakening
What type of hormones play a crucial role in matuation of alveoli and production of surfactant?
glucocorticoids
T/F. Rise in glucocoirticoids (cortisol) production in fetus in final months of pregancy parallels the maturation of lung and production of surfactant.
True
What are the steps/path needed to get to cortisol secretion?
Hypothalmic CRH (corticotropin-releasing hormone) –> anterior pituitary ACTH (adrenocorticotropic hormone) –> adrenal cortisol
T/F. Cortisol stimulates CRH release and therefore ACTH secretion is stimulated too.
False!!! Cortisol INHIBITS CRH and therefore ACTH is inhibited too
NEGATIVE FEEDBACK
How often is cortisol secreted?
secretion is pulsatile and diurnal (daily)
- 10 secretory burst/24 hours
When do the lowest secretory rates of cortisol take place? When do the highest rates take place?
lowest = during evening hours and just after falling asleep
highest = just before awakening in the morning
What is the cortisol/cortisone shuttle
metabolic transformation of steroid hormones are NOT confined to the gland of origin
- therefore may cont to increase or decrease or change biological activity after secretion
What can be used to convert cortisol to cortisone and vice vera? Which is active, which is inactive?
11-beta hydroxysteroid dehydrogenase
cortisol = active cortisone = inactive (therefore get cortisone shots)
What does the direction of cortisol/cortisone depend on?
redox state:
Oxidize cortisol –> cortisone
Reduce cortisone –> cortisol
What is Dexamethasone (DXS)?
a synthetic glucocorticoid that has all the actions of cortisol
What is Dexamethasone (DXS) used for?
a suppression test; test inds. with hypercortisolism to determine the cause if it is a tumor of the anterior pituitary or adrenal tumor
What should happen in a healthy person when given Dexomethasone?
- in healthy ind. a low does of DXS will inhibit ACTH and therefore decrease cortisol
When testing someone with hypercortisolism using Dexamethasone (DXS), and neither low nor high does suppresses cortisol secretion, what is this indicative of?
adrenal cortex cortisol secreting tumor
When testing someone with hypercortisolism using Dexamethasone (DXS), what will be the signs if it is a ACTH secreting tumor of the anterior pituitary gland?
Low does–> doesn’t suppress cortisol secretion
High does–> does suppress cortisol secretion
What are factors that stimulate ACTH secretion?
- decrease blood cortisol levels
- sleep-wake transition
- stress, surgery, trauma
- hypoglycemia
- psychiatric disturbances
- ADH
- serotonin
- alpha-adrenergic agonists
- beta-adrenergic antagonists
What are factors that inhibit ACTH secretion?
- increase cortisol levels
- opioids
- somatostatin
What is the major mineralcorticoid in the body? Where is it synthesized?
aldosterone; synthesized in the zona glomerulosa (which has aldosterone synthase and lacks 17-alpha hydroxylase
What is the primary regulation of aldosterone?* What is this regulation sensitive to?
What has a secondary effect on aldostertone secretion?
renin-angiotension-aldosterone system
which is sensitive to a change in ECF volume
ACTH
We know the renin-angiotension-aldosterone system is the primary regulation of aldosterone, but what peptide hormone is of importance?
Angtiotension II, which will stimulate choelsterol desmolase and aldosterone synthase to make aldosterone
What are the three functions of aldosterone (the main mineralcoritcoid)?
- Control ECF volume
- Control of plasma K+ conc.
- It will increase H+ secretion (renal alpha-intercalated cells)
Describe how aldosterone controls ECF volume.
decrease ECF volume –> decrease renal perfusion pressure –> increases renin secretion by JG cells –> catalyzes conversion of angiotensinogen (in liver) –> to angiotensin I (inactive) –> (in lung) conversion to angtiotenion II –> stimulates aldosterone synthesis (in zona glomerulosa) –> and Na+ and H2O reabsorption occurs (in principal cells)
Describe how aldosterone controls plasma K+ concentration.
increase K+ conc. —> increase aldosterone secretion –> increase K+ excretion by kidney (principal cells)
When there is Aldosterone in excess, what occurs? What disease is this all characteristic of?
Increase: - Na+ reabsorption - K+ secretion - H+ secretion - ECF volume (expansion) Cause: - hypertension - hypOkalemia (b/c get ride of K+) - metabolic alkalosis (b/c get rid of H+)
Conn’s Disease
What will a deficiency in Aldosterone cause?
Decrease in: - Na+ reabsorption - K+ excretion - H+ excretion - ECF volume (contraction) Causes: - HypOtension - Hyperkalemia (b/c cannot get rid of K+) - Metabolic acidosis (b/c cannot get rid of H+)
When you see the word “metabolic” what should you think?
KIDNEY!
T/F. Renal mineralocorticoid receptors bind cortisol and aldosterone with equal affinity.
True
Why doesn’t cortisol overwhelm and prevent aldosterone mineralcorticoid effects since cortisol is higher in conc. circulation over aldosterone? *
- renal cells contain enzyme 11-beta=hydroxysteroid dehydrogenase–> which converts cortisol to cortisone
- –and cortisone have a LOW affinity for mineralcorticoid receptors
What are the type of Androgens hormones?
DHEA (dehydroepiandrosterone) and Androsenedione
When DHEA and Androsenedione get to the testes, what are they converted into?
testosterone
What can be measured in the urine to distinguish DHEA and Androsenedione from cortisol, aldosterone, and testosterone?
17- ketosteroids (ketone group at C17)
T/F. In males adrenal androgens play a major role, and in females they play a minor role.
False.
- In males they play a MINOR role b/c synthesis of testosterone in testes from cholesterol is greater than conversion from adrenal androgens
- In females they play a MAJOR role/ are the major androgens (pubic and axillary hair)
What are the 7 possible pathophysiology issues associated with the adrenal cortex?
- Addison’s disease
- Secondary Adrenocortical Insufficiency
- Cushing’s syndrome
- Cushing’s disease
- Conn’s syndrome
- 21-beta- hydroxylase deficiency
- 17-alpha-hydroxylase deficiency
What is the primary adrenocortical insufficiency disease?
Addison’s disease
What disease is characterized by an autoimmune destruction of the entire adrenal cortex?
Addison’s disease
–therefore decreased synthesis of all adrenocortical hormones
What MC causes Secondary Adrenocortical insufficiency?
insufficient ACTH –> therefore not stimulating cortisol release
What adrenal disease is characterized by hypoglycemia, weight loss, weakness, hyperkalemia, hypotension, metabolic acidosis, salt cravings, decrease in pubic/axillary hair, and has hyperpigmentation of the skin?
Addison’s disease
We know Addison’s DIsease causes decrease synthesis of all adrenocortical hormones, but what chacteristics all under these categories of decreased:
- glucocorticoids
- mineralcorticoids
- adrenal androgens in women
- hypoglycemia, anorexia, weight loss, vomiting, weakness
- hyperkalemia, metabolic acidosis, hypotension
- decrease pubic/axillary hair and libido
Secondary Adrenocortical Insufficiency has the same symptoms as______, except what?
Addison’s disease
Except:
- ACTH levels are high
- No hyperpigmentation
With adrenocotical insufficiency, what is the most likely cause of death? (2)
- circulatory collapse, secondary to Na+ depletion
2. when food intake is inadequate, death may result from hypoglycemia
What disorder is characterized by chronic excess of glucocorticoids due to spontaneous overproduction of cortisol by adrenal cortex or pharmacologic overdose?
Cushing’s Syndrome
What are physiological characteristic features of Cushing’s syndrome?
- hyperglycemia
- decrease sensitivity to insulin and increase tendency for fat mobilization
- hypertension
- osteoporosis
- **low ACTH due to neg. feedback from cortisol (DXS test)
What are physical characteristics of Cushing’s Syndrome?
- increase proteolysis and muscle wasting
- mood face, central (trunk) obesity, buffalo hump
- poor wound healing
- striaee (due to loss of CT)
- females–virilization and menstrual disorders
How does Cushing’s Disease differ from Cushing’s syndrome?
- due to hypersecretion of ACTH from a PITUITARY ADENOMA
- same symptoms as Cushing’s syndrome, EXCEPT ACTH is high
What is caused by an aoldosterone secreting tumor and is therefore a primary hyperaldosteronism?
Conn’s Syndrome
What does Conn’s Syndrome cause?
(anything that will increase due to aldosterone)
Increase:
- ECF volume (inhibits renin release and therefore circulating renin low)
- Na+ and H2O reabsorption (hypertension)
- H+ excretion (metabolic alkalosis)
What could a 21-beta-hydroxylase deficiency cause the adrenals to not produce?
mineralocorticoids (aldosterone) or glucocorticoids (cortisol)
Without 21-beta-hydroxylase enzyme, what is the adrenal cortex unable to do?
convert 17-hydroxyprogesterone to 11-deoxycorisol
What affect will a 21-beta-hydroxylase deficiency have on the adrenal andogrens? What will this cause?
increased production (b/c cannot be use progesterone to make the others)
- virilization in females
- increased urinary levels of 17-ketosteroids
What affect will a 21-beta-hydroxylase deficiency have on ACTH levels? What will this cause?
ACTH levels will be high due to lack of negative feedback due to low cortisol
causing adrenalcortical hyperplasia
T/F. 17-alpha- hydroxylase deficiency is more common than 21-beta-hydroxylase deficiency.
False
What disorder is characteristic of decease in androgens and glucocorticoids?
17-alpha- hydroxylase deficiency
will increase precursors mineralcorticoids—like 11-DOC and corticosterone
17-alpha- hydroxylase deficiency will increase what adrenal cortex hormones? Therefore what will result?
mineralocorticoids precursors like 11-DOC and corticoids
- hypertesion
- hypokalemia
- metabolic alkalosis
The hypertension caused by 17-alpha- hydroxylase deficiency with due what?
decrease aldosterone and therefore inhibit renin secretion –> leading to decrease in angiotension II and therefore decrease aldosterone
(which is weird to think about–chart)
__ percent of patients with Cushing’s disease are also diabetic and most of the rest have some milder impairment of glucose metabolism.
20%
Prolonged exposure to increased glucocorticoids results in what disease? What other disorder can this lead to?
Cushing’s disease
may lead to diabetes mellitus
The Adrenal medulla is ____ percent of mass of the adrenal gland.
10-20%
Cells of the adrenal medulla have affinity for chromium salts are called what?
chromaffin cells (modified postganglionic neurons of sympathetics)
How does the secretion of catecholamines occur?
axons from the intermediolateral horn cells in thoracolumbar spinal cord pass through paravertebral sympathetic ganglia –> splanchic nerves then synpase with chromaffin cells which secrete Epi and NE
What percentage are catacholamines from the adrenal medulla secreted in?
80% Epinephrine
20% Norepinephrine
What else does the adrenal medulla secrete when stimulated by axons of IML, besides Epi and NE?
secretes neuropeptides:
- adrenomedullin (vasodilator) and
- beta enkephalin (opioid)
Which part of the adrenal gland plays a crucial role in acute response to stress?
adrenal medulla
T/F. The adrenal medulla is not required for survival if the rest of the SNS is intact.
true
The adrenal medulla is an extension of the _____.
SNS
What is the precursor for Epinephrine from beginning to end?
Tyrosine –> DOPA –> Dopamine –> NE –> Epi
Up to __ percent of the catecholamines are removed in a single passage through most capillary beds.
90%
T/F. Catecholamine uptake is only neuronally.
False–it is both neuronally and non-neuronally
What degrades the catecholamines in neuronal cytosol?
mono-amine oxidase (MAO)
What inactivates the catecholamines enzymaticaly in the endothelium of the heart, liver, and other tissues?
COMT (catecholamine-O-methyl-transferase)
What physiological effects do the medullary hormones have on:
- Heart
- Blood vessels
- Metabolism–
- Kidney
- Skeletal Muscle
- CNS
- increase rate and force of contraction and glycogenolysis
- vasoconstriction
- a lottttt
- increase renin secretion and sodium reabsorption
- increase muscle tension and neuromuscular transmission
- senses keener, memory sharper, less sensitive to pain
What physiological effects do medullary hormones have on metabolism: 1. Adipose 2. Liver 3. Muscle 4. Lungs 5. Stomach and Intestines 6. Skin
- increase lipolysis and blood FFA and glycerol
- increase glycogenolysis and gluconeogenesis and increase blood sugar
- increase glycogenolysis and lactate and pyruvate release
- dilation of bronchioles
- inhibit peristalisis; and increase sphincter contraction
- increase sweating
What is cholesterol turned into that is also considered a precursor for all steroid hormones?**
pregnenolone
