What is the functional anatomy of the adrenal glands?
2 adrenal glands
4 grams each
Located at superior pole of kidney
What are the 3 parts of the adrenal cortex?
Zona glomerulosa
Zona fasciulata
Zona reticularis
Name the two parts of the adrenal glands and the respective percentages
Adrenal medulla (inner 20%)
Adrenal cortex (outer 80%)
TRUE or FALSE. Adrenal medulla is functionally a SNS ganglion.
FALSE
Describe the Zona glomerulosa
Outermost 15% of the cortex
Secretes aldosterone
Describe the Zona fasciulata
Middle & largest layer (75% of cortex)
Secretes glucocorticoids cortisol & corticosterone & small amount of androgens & estrogens
ACTH stimulates secretion
Describe the Zona reticularis
Deepest layer
Secretes androgens (DHEA), small amounts of estrogens & glucocorticoids via ACTH
What does the zones of the adrenal cortex have to do with the way aldosterone and cortisol are regulated?
Because of the way the adrenal cortex is zoned, aldosterone and cortisol secretion are independently regulated so that Angiotensin II will only stimulate the zone of glomerulosa. ACTH has no effect on that zone (does effect Zona fasciulata and Zona reticularis)
What are the mineralcorticoids of the adrenal cortex? (there are six)
Aldosterone (90%)
Desoxycoticosterone
Corticosterone9
α Fluorocortisol (synthetic)
Cortisol
Cortisone (synthetic)
What are steroid hormones derived from?
Cholesterol.
80% of cholesterol comes form the low density lipoprotein in the plasma.
Aldosterone is major one.
What does Aldosterone (a mineralcorticoid) do?
It will increase Na reabsorption and K+ secretion by the renal tubules.
Holds onto Na and passively also holds onto water.
The mineralo- refers to effect on Na and K.
What happens when there is excess aldosterone?
↑ ECF volume → ↑ BP → pressure natriuresis & pressure diuresis → ↑ renal excretion of sodium & water = aldosterone escape
↓Potassium
↑hydrogen ion secretion by renal tubules → mild alkalosis
How much does BP have to increase before we get pressure naturiesis and diuresis?
15-25mmHg
So when aldosterone increases ECF and BP, we get excretion of the Na and water it was holding onto
How low can K+ go with excessive aldosterone secretion?
hypokalemia down to a level of 2mEq/L can occur
(Cardiac irritability, muscle weakness, etc).
What are the two most important stimuli for the synthesis and release of aldosterone?
↑ ECF potassium → ↑ aldosterone
↑ renin-angiotensin activity → ↑ aldosterone
Besides the two important stimuli, what else can regulate the synthesis and release of aldosterone?
↑ ECF sodium → sl ↓ aldosterone
ACTH is necessary for aldosterone secretion but doesn’t control rate of secretion
Describe the HPA axis and the effects on the adrenal cortex
Refers to the fact that corticotropic releasing factor (produced and released by hypothalamus) will stimulate release of ACTH from the anterior pituitary.
Then ACTH from anterior pituitary will stimulate synthesis of glucocorticoids by the adrenal cortex.
The glucocorticoids from adrenal cortex will provide negative feedback for both ACTH and the corticotropic releasing factor.
How will glucocorticoids will affect metabolism?
stimulate proteolysis and gluconeogenesis, and they’ll increase fatty acid mobilization
List all the glucocorticoids from the adrenal cortex? (there are six)
Cortisol (95%) 20 mg secreted daily
Corticosterone (4%)
Prednisone (synthetic, 4 X as potent as cortisol)
Cortisone (synthetic, almost as potent as cortisol)
Methylprednisone (synthetic, 5 X as potent as cortisol)
Dexamethasone (synthetic, 30 times as potent as cortisol)
Describe the rhythmic release of cortisol
Release of cortisol is pulsatile and under direct stimulation of ACTH.
It follows the circadian rhythm, sensitive to light, sleep, stress, and disease.
We secrete the most cortisol in early waking hours and the levels decline as the day progresses
There are four synthetic types of glucocorticoids, list them in order of least to most potency when compared to cortisol
Cortisone (synthetic, almost as potent as cortisol)
Prednisone (synthetic, 4 X as potent as cortisol)
Methylprednisone (synthetic, 5 X as potent as cortisol)
Dexamethasone (synthetic, 30 times as potent as cortisol)
What causes the slow elimination of cortisol from the plasma?
Most of cortisol is bound to plasma protein.
So that slows the elimination from the plasma
What is the effect of cortisol on CHO metabolism?
Stimulation of gluconeogenesis
↓ utilization of glucose by cells
Hyperglycemia & ↑ insulin levels
Cause insulin resistance, develops diabetes
What is the effect of cortisol on protein metabolism?
Reduction in cellular protein → muscle weakness (Decreased synthesis & Increased breakdown)
Increased liver & plasma proteins
Increased amino acids & transport to hepatic cells
What is the effect of cortisol on the fat metabolism?
Mobilization of fatty acids
Obesity
Centripedal obesity, moon face, etc
Describe Cortisol and the stress response
Stress causes ↑ ACTH by the anterior pituitary
ACTH → ↑ cortisol by adrenal cortex
Proteins are mobilized & broken down to make amino acids available to synthesize substances needed to sustain life
Anti-inflammatory effects
Describe the two mechanisms of the anti-inflammatory response and cortisol
Blocks early stages of inflammatory response
Causes rapid resolution of inflammation
How does cortisol block the early stages of inflammatory response?
Stabilizes lysosomal membranes
Decreases capillary permeability
Decreases WBC migration & phagocytosis
Suppresses immune system
Attenuates fever 2° ↓ interleukin-1 from WBCs
Primary aldosteronism (aka Conn’s syndrome, hyperaldostoerone syndrome) causes mineralcorticoid excess. What are the causes of this?
Unilateral adenoma
Bilateral hyperplasia
Carcinoma of adrenal gland
What is the cause of secondary aldosteronism?
Stimulation of aldosterone secretion by affecting renin-angiotensin system
stimulus of RAAS could be congestive heart failure or decreased blood volume, cirrhosis, renal artery hypertension where there is increased renin activity.
What are the s/s of mineralcorticoid excess?
HTN
Hypervolemia
Hypokalemia
Muscle weakness(common w/endocrine)
Metabolic alkalosis
Polyuria (common w/endocrine)
Decreased ionized calcium → tetany
Patients are commonly obese.
Hyperglycemia occurs in about 50% of patients
What are the anesthesia implications for mineralcorticoid excess?
Correct fluid & electrolyte disturbances (hypernatremia, hypokalemia, as well as elevated blood sugar)
Patient may also have a decrease in gastric pH, H2 blocker may be beneficial pre-op.
A-line may be helpful, possibly a CVP.
Hypokalemia so may have a potentiation of the neuromuscular blockade.
D/t elec. disturbances they could have a prolonged emergence from anesthesia.
Already have metabolic alkalosis, avoid hyperventilating them.
What could cause mineralcorticoid deficiency?
Atrophy or destruction of adrenals
Unilateral adrenalectomy
Diabetes mellitus
Heparin therapy
What are the s/s of mineralcorticoid deficiency?
Hyperkalemia
Acidosis
hypotension
What are the anesthesia implications of mineralcorticoid deficiency?
give exogenous hormone (fludrocortisone)
Hyperadrenalism is mostly due to excess...
glucocorticoid (Cortisol)
CUSHING'S SYNDROME
Cushing's syndrome can have dependent or independent causes. What are the dependent causes?
Means it’s dependent on excess ACTH or potentially corticotropic releasing hormones
Abnormality of hypothalamus (excess CRH)
Pituitary tumor (excess ACTH) = Cushing’s disease
Ectopic tumors (excess ACTH
Cushing's syndrome can have corticotropin dependent or independent causes. What are the independent causes?
independent of ACTH levels. This is d/t some abnormality of adrenal cortical tissue itself.
Adenomas of adrenal cortex
Exogenous glucocorticoid administration
TRUE or FALSE. Pituitary tumor w/excess ACTH Cushing’s disease is the least common form of Cushing’s syndrome
FALSE. It is the MOST COMMON FORM
What are the anesthetic implications of hyperadrenalism (glucocorticoid excess)?
Consider physiologic changes with ↑ cortisol
Glucocorticoid deficiency can be d/t primary or secondary adrenal insuficiency. If it is a primary adrenal insufficiency, it is Addison's. Describe this.
Rare
Deficiency of glucocorticoids, mineralocorticoids, & androgens
From destruction of adrenal (autoimmune)
May be an autoimmune situation (80% of cases is autoimmune)
Could also be cancer destroying the tissue.
What is considered a primary adrenal insufficiency? (cortisol level less than...)
Baseline cortisol level of less than 20mcg/dL.
In adrenal insufficiency, ___% of the adrenals has to be involved for it to cause adrenal insufficiency.
90%
What are the s/s of primary adrenal insufficiency (Addison's)?
Here there is often a deficiency of cortisol and aldosterone
Can a person die from primary adrenal insufficiency?
YES, if there is total destruction of adrenal cortex pt will die due to circulatory collapse.
What causes secondary adrenal insufficiency?
From ↓ secretion of CRH or ACTH
Effectively suppression of the HPA axis.
This may be d/t radiation, pituitary surgery, or most commonly, because of chronic steroid administration
If a patient has been on steroids chronically, what should we think about?
Consider if they are at risk for suppression of HPA axis (Stress of surgery needs more cortisol)
If suppression pt may not be able to release excess cortisol so may need to give exogenous steroids.
What are the anesthetic concerns for a patient w/Addison's?
Pt would be hyperkalemic, acidotic and saliva may be acidotic, may have dental decay and loose teeth so be careful w/airway assessment.
Need to correct volume and any electrolyte abnormalities ( likely to be increase K, decreased sodium, and decreased glucose) and monitor for arrhythmias because of electrolyte abnormalities.
We produce __mg of cortisol daily. Under the stress of surgery, don’t produce any more than about ___mg/day
20; 150
How much the HPA axis is stimulated is dependent upon...
nature of the surgery & the magnitude the duration
ACTH will usually stay elevated, will increase w/incision and stay elevated, the peak occurring at the time of muscle relaxant reversal and extubation.
Constantly peaking throughout the surgery
Regarding steroid administration in the OR, most agree to supplement for those who have been on steroids for ___ weeks in the last_____M.
1-2 weeks in the last 6-12M.
What does Stoelting recommend regarding steroid supplementation?
Superficial surgery; dental; biopsy (None)
Minor surgery; inguinal hernia (25 mg IV)
Moderate surgery; cholecystectomy (50-75 mg IV, taper 1-2 days)
Severe surgery; cardiovascular (100-150 mg IV, taper 1-2 days)
ICU; sepsis, shock (50-100 mg q 6-8 hr for 2 days – 1 week, taper)
If there is HPA axis suppression, why do we give cortisol supplementation but not aldosterone?
giving NaCl so don’t’ need to give aldosterone
Why is Etomidate contraindicated in adrenal insufficiency?
It inhibits the synthesis of cortisol transiently
What three hormones are released by the adrenal medulla?
Epinephrine – 80% (Can increase metabolic rate of body by as much as 100% above normal & Longer duration of action)
Norepinephrine – 20%
Dopamine
Epi increase the metabolic rate of body by how much ?
as much as 100% above normal
Also the effect of adrenal medulla stimulation is identical to SNS stimulation except ......
it has a longer duration of action (5-10x longer).
What is a pheochromocytoma?
Catecholamine secreting tumor (epi, norepi)
What % of pheochromocytomas are malignant?
10-15% are malignant
What % of pheochromocytomas are bilateral or extra adrenal?
10-15% are bilateral or extra-adrenal
What % of pheochromocytoma are in the adrenal medulla?
90% are in adrenal medulla (More than 95% are intraabdominal---90% in the adrenal medulla)
What is the age of presentation of a pheochromocytoma?
Age at presentation 30-50
What are the s/s of pheochromocytoma?
HTN, diaphoresis, headache, palpitations, weight loss (triad = diaphoresis, tachycardia, headache in the hypertensive patient)
If triad isn’t there, pheo is unlikely
Hypovolemia
What is the triad in a pheochromocytoma?
triad = diaphoresis, tachycardia, headache in the hypertensive patient
If it's not there, pheochromocytoma is unlikely
How do we diagnose a pheochromocytoma?
by a 24hr urine for free (unconjugated) epi and norepi as well as metabolites & vanilylmandelic acid.
Clonidine suppression test, clonidine will suppress catecholamine levels in essential HTN and not in pheochromocytoma
What is a REALLY important thing about pheochromocytoma pre-op?
One of the things that is REALLY important is the patient be alpha blocked pre-op
Tell me about Phenoxybenzamine in regards to pheochromocytoma
Use phenoxybenzamine 10-20mg BID for 10-14 days pre-op.
Causes that irreversible alpha blockade.
When do we beta block our patient w/a pheochromocytoma
Can only establish beta blockade after alpha blockade has been established
The need to block alpha receptors 1st is so we can essentially vasodilate and correct the volume situation 1st
If we beta block 1st, the betablock myocardium the may not be able to eject against the high SVR
What do we want to avoid with a pheochromocytoma?
Avoid SNS stimulating drugs
Avoid volatiles that sensitize the myocardium to epi
What can happen with the patient who had a pheochromocytoma during the post-op period?
patient can be hypotensive.
May develop CHF.
Can actually have psych changes because of the decreased catecholes.
What should you have available for a pheochromocytoma?
Have sodium nitroprusside (Nipride) and dopamine available but might be exaggerated responses to those drugs
What is Multiple endocrine neoplasia?
Autosomal dominant multiglandular disorder
Patient were to present thyroid surgery for medullary thyroid cancer, want to think do they have underlying pheo.
Or if the patient has a parathyroid adenoma, think pheo.
Those kinds of things can be associated w/pheochromocytoma.
Bear in mind if pt is coming in for some sort of endo disorder do they also have something more dangerous (undiagnosed pheo)
