Adrenals Flashcards
What hormones does the zona glomerulosa produce ?
Mineralocorticoids (aldosterone)
what hormones does the zona fasciculata produce?
glucocorticoids: cortisol
what hormones does the zona reticularis produce?
androgens
what does the adrenal medulla produce?
catecholamines (epi and NE)
Aldosterone release is caused by:
RAAS activation
Hyperkalemia
Hyponatremia
aldosterone stimulates the kidney to conserve____ and ____ and excrete ____ and ____
conserve: sodium and h2O
excrete: K+ and H+
T/F: aldosterone regulates sodium concentration and osmolarity
FALSE! it does NOT regulate sodium concentration or osmolarity
What increases cortisol production?
Stress
Increased cortisol initiates:
gluconeogenesis
protein catabolism
fatty acid mobilization
Cortisol lessens (mitigates) the ____ cascade by reducing ______ release
lessens the inflammatory cascade
reduces cytokine release
cortisol improves _____ performance and is required for vasculature to respond to the vasoconstrictive effects of ______
myocardial performance
catecholamine
Adrenal Medulla synthesizes what two catecholamines in what amounts?
Epinephrine (80% of catecholamine output )
Norepinephrine (20% of catecholamine output)
What stimulates renin release?
-decreased renal perfusion (hemorrhage, PEEP, CHF, Liver failure, sepsis)
-SNS activation (beta-1)
-tubuloglomerular feedback
What kind of cells release renin?
Juxtaglomerular cells
ACTH only has _____ influence on aldosterone release.
minor
Thus explains why decreased ACTH does not cause hypoaldosteronism
the reabsorption of sodium and excretion of potassium and hydrogen by aldosterone causes:
1.) Fluid retention and expansion of extracellular space
2.) Decreased serum potassium concentration
3.) Metabolic alkalosis
T/F: aldosterone regulates sodium concentration and osmolarity
FALSE!
aldosterone regulates intravascular volume
T/F: sodium concentration does not change due to aldosterone
TRUE!
When sodium is reabsorbed into the peritubular capillaries, water follows in direct proportion= the sodium concentration does not change
What is osmolarity and sodium concentration controlled by?
ADH
ADH increases the reabsorption of _____ but NOT _____
water but NOT sodium
Increased water reabsorption dilutes sodium, and reduced water reabsorption concntrates sodium
T/F: cortisol does not interact with membrane-bound receptors
TRUE
It diffuses through the lipid bilayer and then binds with intracellular steroid receptors
T/F: cortisol influences protein synthesis inside the target cell
TRUE: cortisol activates or inhibits DNA transcription
these process require time, which explains the relatively slow onset of steroid medications
What is the normal cortisol production per day?
15-30 mg/day with a normal serum level of 12 mcg/dL
With stress what levels of cortisol will you see?
upwards of 100mg/day, with serum level up to 30-50mcg/dL during and after major surgery
How does cortisol produce energy mobilization?
Gluconeogenesis (amino acids are converted to glucose by the liver= increase blood sugar)
Protein catabolism (mainly muscle breakdown) = increased amino acid availability to the liver for gluconeogenesis
Fatty acid mobilization = increased FFA oxidation = increased ability to use fat for energy instead of glucose
How does cortisol produce anti-inflammatory effects?
Mitigates the inflammatory cascade by stabilizing lysosomal membranes and reducing cytokine release
- decreases # of esoinophils and lymphocytes in the blood
-cortisol does NOT reduce histamine release during an antigen-antibody response (accomplished by epi at the beta-2 receptor on mast cells and basophils)
What are the hemodynamic affects of cortisol?
Improves myocardial performance by increasing the number and sensitivity of beta receptors on the myocardium.
-Cortisol is also required for the vasculature to respond to vasoconstrictive effects of catecholamine
What are the hemodynamic affects of cortisol?
Improves myocardial performance by increasing the number and sensitivity of beta receptors on the myocardium.
-Cortisol is also required for the vasculature to respond to vasoconstrictive effects of catecholamine
Order each drug in terms of its glucocorticoid potency
cortisol
dexmethasone
methylprednisolone
aldosterone
1.) dexamethasone
2.) methylprednisolone
3.) cortisol (equal glucocorticoid and mineralcorticoid effects)
4.) aldosterone
Match each disease to its underlying pathophysiology
Conn’s syndrome
Cushing’s syndrome
Addison’s disease
excess aldosterone
excess cortisol
inadequate cortisol
Cushing’s syndrome = excess cortisol
Addison’s disease = inadequate cortisol
Conn’s syndrome = excess aldosterone
Etiologies of primary hyperaldosteronism (Conn’s syndrome)
Excessive aldosterone release from the adrenal gland- can be caused by adrenocortical hyperplasia or carcinoma
aldosteronoma
pheochromocytoma
primary hyperthyroidism
What will you see with Conn’s syndrome (to much aldosterone)
HTN
HYPOkalemia (u-waves and arrhythmias)
Hypokalemic metabolic alkalosis
increased extracellular fluid volume
DECREASED RENIN levels
What is the treatment for Conn’s syndrome?
surgical removal/medical management
-K+ supplementation
-antihypertensives
-spironolactone
-Eplerenone
- laparoscopic adrenalectomy
TX: FLUID AND SODIUM RESTRICT
will have weakness d/t hypokalemia= sensitive to all paralytics
What causes secondary hyperaldosteronism?
Stimulus of excess aldosterone outside the adrenal gland:
CHF
cirrhosis
ascites
nephrosis
exacerbates fluid and sodium retention
What are the symptoms of secondary hyperaldosteronism?
Increased renin levels
intravascularly dry
fluid volume overload
What is primary adrenocortical insufficiency called?
Addison’s disease
What causes Addison’s disease?
Mostly autoimmune destruction of the gland
Can be caused by infectious disease: TB, AIDS, fungal infections
What is insufficient in Addison’s disease?
Androgen, glucocorticoid and mineralcorticoids
What is intact in Addison’s disease?
HPA axis (adrenal-pituitary axis)
Are ACTH levels high or low in Addison’s disease?
ACTH concentrations are high d/t decreased cortisol
What is the treatment for Addison’s disease?
Replace glucocorticoids (anti-inflammatory) and mineralocorticoids (salt retention) = HYDROCORTISONE and FLUDROCORTISONE
Which steroid hormone has effects in virtually all cells in the body?
Glucocorticoids
With a total loss of _______ secretion, death would ensue within days without treatment
Mineralcorticoids (aldosterone)
What are the clinical features you would see in Addison’s disease?
-Weakness/fatigue
-decreased appetite/ wt/ loss
-Vomiting/Diarrhea
-Abdominal pain
-HYPOglycemia
-HoTN
-HYPOnatremia
-HYPERkalemia
-Hyperpigmentation
- Azotemia
What is another name for acute adrenal crisis?
Addisonian crisis
What are the clinical features of an acute adrenal crisis?
-weakness
-nausea
-HoTN
-fever
-decreased mental status
- HYPERkalemia
-HYPOnatermia
-manifests as hemodynamic instability and cardiovascular collapse
Treatment for acute adrenal crisis:
5% dextrose and hydrocortisone
What is secondary adrenocortical insufficiency?
decreased glucocorticoids (cortisol)
ACTH deficiency
HPA axis suppression/hypothalamic or pituitary dysfunction
mineralcorticoids (aldosterone secretion intact)
Features of secondary adrenocortical insufficency:
Wt. loss
weakness/fatigue
HYPOglycemia
treatment for secondary adrenocortical insufficiency:
just glucocorticoids
What causes Cushing’s syndrome?
cortisol excess
Causes of Cushing’s syndrome:
can be ACTH-dependent or independent or iatrogenic (administration of glucocorticoids for arthritis, allergies, or asthma) or adrenal hyperplasia
Symptoms of Cushing’s syndrome (cortisol excess)
-Muscle atrophy
-thin skin
- central obesity
-thin extremities
-florid complexion
-moon facies
-purplish striae
-muscle weakness
-easy bruising
-HYPERglycemia
-HTN
-increased susceptibility to infection
-HYPOkalemia
-ALKALOSIS
-hirsutism
-osteoporosis
-cataracts
-mood disorders
-OSA
What can Cushings be diagnosed with?
Dexamethasone
What is the treatment for Cushing’s syndrome?
Surgical removal of pituitary corticotrope tumor
-Spironolactone
What is one of the body’s most significant protectors of volume status?
the RAAS
Renin is released in response to:
HYPOvolemia
SNS stimulation
HoTN
HYPOnatremia
Aldosterone’s primary target cells are called:
PRINCIPAL CELLS
located in the distal convoluted tubule and cortical collecting ducts
What controls aldosterone secretion?
1.) Serum POTASSIUM- potent controller
2.) angiotensin II- potent controller
3.) (low) Serum sodium- minor effect
4.) ACTH- minor effect
(acetylcholine, serotonin)
what is cortisol inactivated by and excreted as?
inactivated by the liver and kidneys
excreted in the urine as 17-hydroxycorticoids
Cortisol binds to_____ receptors in the target cells and alters gene ______ & _____
intracellular receptors and alters gene transcription and translation
where do mineralcorticoids work?
renal distal tubule and salivary and sweat glands
When should etomidate not be used?
Addison’s/ any adrenal crisis/ adrenal insufficency
When would prednisone be good to use?
Prednisone is an analog of cortisol, making it a good choice to treat adrenocortical insufficiency (Addison’s disease)
cortisol=
HYDROCORTISONE
(controlled by ACTH/corticotropin)–> which is controlled by corticotropin-releasing hormone (CRH) from the hypothalamus) & arginine vasopressin
When cortisol levels are high the feedback system:
Inhibits the release of ACTH from the anterior pituitary and CRH from the hypothalamus
ACTH deficiency=
adrenal gland atrophy
(ACTH also controls adrenal gland growth)
What time of day is the most cortisol produced?
Most is produced and released in the morning
What stimulates ACTH?
-CRH
-sleep to wake period
-Stress
-HYPOglycemia
-HoTN
-Sepsis
-Trauma/Burns
- decreased plasma cortisol
-Alpha- adrenergic receptor stimulation
NE is converted to EPi in the adrenal medulla by:
Phenylethanolamine-N-methyltransferase (PNMT)
What stimulates PNMT?
High concentrations of glucocorticoids
What oxidized NE and epi to vanillymandelic acid (VMA)
Monoamine oxidase (MAO)
What will be seen in the urine of someone with pheochromocytomas?
increase VMA, metanephrine and normetanephrine
What is the triad of symptoms in Pheochromocytomas?
Diaphoresis
Tachycardia
Headache in hypertensive pts (proxysmal HTN)
will also see hyperglycemia and increased O2 consumption, anxiety, tremor, sweating
What drug should be avoided in pheochromocytomas?
Avoid morphine d/t histamine release
also avoid metoclopramide and glucagon
What drugs should be used for pheochromocytoma?
Alpha-adrenergic blockers for 10-14 days pre-op
Phenoxybenzamine or prazosin
after adequate alpha blockade, beta blocker can begin - want to delay that bc of the risk of unopposed alpha mediated vasoconstriction
Anesthetic plan for adrenalectomy:
A-line
central venous access
intra-op TEE
Avoid histamine-releasing drugs:
-metoclopramide
-glucagon
Which of the following is consistent with Cushing’s syndrome?
A. Increased risk for deep vein thrombosis
B. Resistance to muscle relaxants
C. Hyperkalemia
D. Hypoglycemia
A. Increased risk for deep vein thrombosis
will have HYPOkalemia and HYPERglycemia, muscle relaxants will have an exaggerated response
Which of the following conditions refers to the excess secretion of glucocorticoids due to a pituitary tumor?
A. Cushing disease
B. Cushing syndrome
C. Addison’s disease
D. SIADH
A. Cushing disease
Cushing syndrome refers to the symptoms that result from excess corticosteroids of any cause. Cushing disease refers to Cushing syndrome that is cause by the oversecretion of ACTH by a pituitary tumor.
Chronic administration of exogenous glucocorticoids can suppress the HPA axis and produce
A. diabetes insipidus
B. adrenal insufficiency
C. primary hypoaldosteronism
D. diabetes mellitus
B. adrenal insufficiency
Secondary adrenal insufficiency occurs due to suppression of the HPA axis by administration of exogenous glucocorticosteroids or ACTH deficiency due to dysfunction of either the hypothalamus or pituitary gland. Signs of adrenal insufficiency include weakness, hypotension, hyponatremia, hyperkalemia, hypercalcemia, azotemia, and anemia.
The common end product of the metabolism of norepinephrine and epinephrine is
A. monoamine oxidase
B. vanillylmandelic acid
C. catechol-O-methyltransferase
D. metanephrine
B. vanillylmandelic acid
The common end-product of the metabolism of epinephrine and norepinephrine via catechol-O-methyltransferase or monoamine oxidase is vanillylmandelic acid.
Which of the following hormones is derived from cholesterol?
A. aldosterone
B. vasopressin
C. calcitonin
D. triiodithyronine
A. aldosterone
The mineralocorticoids (like aldosterone), glucocorticoids, and reproductive hormones are all steroid hormones and are derived from cholesterol. Vasopressin and calcitonin are peptide hormones and are proteins. Thyroid hormones (like triiodothyronine) and catecholamines are derived from tyrosine.
Signs of Cushing’s syndrome include: (select 4)
-HTN
-HoTN
-Hyperkalemia
-Hypokalemia
-metabolic alkalosis
-metabolic acidosis
-hyperglycemia
-hypoglycemia
HYPERtension
HYPERglycemia
HYPOkalemia
Metabolic alkalosis
will also have decreased serum calcium
Increased parathyroid hormone
What is Cushing’s caused by?
cortisol excess either from overproduction or exogenous administration -
Cushing’s disease is the result of ACTH excess as a result of the PITUITARY GLAND
Cushing syndrome is a result of ACTH release coming from anywhere else
Glucocorticoid effects
Hyperglycemia
wt gain
increased risk of infection
osteoporosis
muscle weakness
mood disorder
Mineralcorticoid effects
HTN
HYPOkalemia
metabolic alkalosis
Androgenic effects
women become masculinized (hirsutism, hair thinning, acne, amenorrhea)
men become feminized (gynecomastia, impotence)
What can be followed by pituitary resection?
Transient diabetes insipidus
List 3 treatments a pt with Cushings might undergo:
1.) transsphenoidal resection
2.) pituitary radiation
3.) Adrenalectomy (if adrenal tumor)
A pt with adrenal insufficiency and sepsis required an emergency intubation in the intensive care unit. Which drug should be avoided?
A. Etomidate
B. Propofol
C. Ketamine
D. Thiopental
A. Etomidate
by inhibiting 11-beta-hydroxylase, a single induction dose of etomidate causes adrenocortical suppression for >8hrs. This could potentially convert adrenal insufficiency to acute adrenal crisis
DON’T USE ETOMIDATE IN SEPTIC SHOCK, EITHER!
When should a patient receive stress dose steroids?
Prednisone or equivalent > 20mg/day for >3 wks = YES
Prednisone or equivalent 5-20 mg/day for > 3 weeks= YES
Prednisone or equivalent <5mg/day for any time period any dose for <3 wks= NO
Renin from the kidney acts on:
angiotensinogen that is secreted from the liver and breaks down angiotensinogen to angiotensin 1
ACE from the lung works on:
angiotensin 1 to make angiotensin 2
pts with adrenal hyperplasia could require what medications?
Spironolactone (aldosterone antagonist= doing the opposite of the excess antagonist)
What is hypoaldosteronism?
Adrenal insufficiency
- Na+ lost in urine, K+ retained
- Plasma volume decreases and hypotension/hyperkalemia may lead to circulatory collapse
TX: STEROIDS
what cells release ACTH?
Corticotroph cells in the anterior pituitary
What are the symptoms Secondary: Hypothalamic or pituitary dysfunction?
Symptoms: (triad)
Hypoglycemia
fatigue/ weakness,
weight loss, anorexia (nearly 100%)
what are the 4 catecholamines?
DOPA
Dopamine
Norepinephrine
Epinephrine
Catecholamines are all derived from the amino acid :
TYROSINE
what kind of neuron is the chromaffin cell?
Post-ganglionic sympathetic neuron
what is fight or flight triggered by?
Pain, fear, hemorrhage, cold, hypoglycemia, hypotension, heat, exercise, surgery
Which areas of the body have increased/decreased CO?
Increased CO to heart and skeletal muscle.
Decreased CO to kidneys, skin, and mucosa
Bronchodilation, increase resps.
Rule of 10s for Pheochromocytoma
10% are bilateral
10% are outside the adrenal gland
(most in abdomen)
-haraganglioma - chromaffin cells on the sympathetic chain- where the aorta bifurcates
10% are malignant
Most tumors (85-90%) are solitary tumors localized to a single adrenal gland (mostly the right)
1/2 of these pts have Multiple Endocrine Neoplasia (MEN) type II
what receptors does phenoxybenzamine block?- non-selective = alpha 1 and 2 long acting
- non-selective = alpha 1 and 2
long-acting
which receptor does prazosin block?
alpha 1
What are the 3 selective beta blockers?
Esmolol
metoprolol
atenolol
