1 - Adrenocortical Hormones Flashcards
The adrenal cortex secretes:
corticosteroids
The adrenal medulla secretes:
Epinephrine and norepinephrine
The three classes of corticosteroids released by the adrenal cortex are:
mineralocorticoids
glucocorticoids
androgens
What is the gross function of mineralocorticoids?
They effect “minerals” aka electrolytes
What is the gross function of glucocorticoids?
increase blood glucose concentration
(also effect protein and fat metabolism)
The principal mineralocorticoid is _________
The principal glucocorticoid is _________
aldosterone
cortisol
Describe the three layers of the adrenal cortex, including what they secrete and how secretion is controlled
- Zona glomerulosa - only cells that secrete aldosterone, secretion of which is controlled by K and Angiotensin II
- Zona fasciculata - middle, widest, secretes cortisol and corticosterone, secretion controlled by ACTH
- Zona reticularis - inner zone, secretes adrenal androgens and small amounts of estrogen and glucocorticoids, regulated by ACTH
Describe the relationship between aldosterone and cortisol secretion
They are completely independently regulated
ACTH has no effect on aldosterone
Angiotensin II has no effect on cortisol
Approximately 80% of the cholesterol used for steroid synthesis is provided by _______
LDLs in circulating plasma
What is the rate limiting step in all adrenal steroid formation?
the cleaving of cholesterol in the cell into pregnenolone by cholesterol desmolase
Synthesis of steroid in the adrenal cortex occurs where in the cell?
mitochondria and ER
How potent is dexamethasone compared to cortisol?
30x more potent
If cortisol primarily effects glucose metabolism, why do high cortisol disease states also include electrolyte imbalances?
Cortisol also has slight mineralocorticoid action
How is cortisol transported in the blood?
90-95% bound to cortisol-binding globulin
How is aldosterone transported in the blood?
60% protein bound
40% free form,
this accounts for its short half life of 20 minutes vs. other adrenocortical hormones (like cortisol)
Where are adrenocortical hormones metabolized?
Metabolized in the liver
inactive conjugates excreted by the liver
What would happen without mineralocorticoids?
Think: without aldosterone
Massive salt wasting and hyperkalemia
Since cortisol has some mineralocorticoid effect, and there’s an enormous concentration of it floating in the plasma, why doesn’t it have a big effect on the kidneys?
renal epithelial cells express 11B-HSD2
prevents cortisol from activating mineralocorticoid receptors
What is Apparent Mineralocorticoid Excess Syndrome?
AME
Happens when the 11b-HSD2 enzymes are deficient, allowing cortisol to bind to mineralocorticoid receptors
looks like hyperaldosteronism, but aldosterone levels are low
What does Aldosterone impact: total sodium or sodium concentration?
TOTAL SODIUM!
Water moves with the sodium, and concentration remains the same
What is aldosterone escape?
only elevates extracellular volume for about two days
As ECF increases, so does GFR
results in pressure natriuresis/diuresis whcih returns the renal output of sodium and water to normal despite excess aldosterone
An increase in aldosterone does not effect sodium concentration, but a decrease does. Why?
Decreased aldosterone leads to massive water loss, which triggers ADH
ADH causes water reabsoprtion but NOT sodium reabsorption
You get a decrease in [Na]
What are the most potent regulators of aldosterone secretion?
[K]
Angiotensin II
95% of the glucocorticoid activity of the adrenal cortex results from the secretion of ________
cortisol/hydrocortisone
What is gluconeogenesis?
formation of carbohydrates from proteins and other substances in the liver
By what 3 modes does cortisol increase gluconeogenesis?
- Activates liver cell DNA transcription to create enzymes required to convert amino acids into glucose
- Moves amino acids from the muscles into the liver
- Antagonizes insulin’s inhibitory effect on gluconeogenesis
Cortisol causes blood glucose to rise for two reasons:
- gluconeogenesis
- decreased glucose utilization by cells
What is adrenal diabetes?
elevated cortisol cuases an increase in blood sugar, and in doing so decreases tissue sensitivity to insulin
The pancreas is working just fine and releases an appropriate amount of insulin, but the tissues are resistant to insulin so the blood sugar remains elevated
the problem isn’t the pancreas, its the cortisol levels
Cortisol reduces the amount of ____ protein, and increases the amount of ______ protein
cellular
liver and plasma
(wants to preserve amino acid consumption, so it reduces the ability of all nonhepatic cells to make proteins)
How does cortisol mobilize amino acid transport to the liver?
It prevents anabolic processes, but it doesn’t effect catabolic protein metabolism. This means cells aren’t producing proteins, but they are still breaking them down. The excess amino acids released and transported via blood to the liver
Cortisol _______ fatty acid mobilization
increases
Why does excess cortisol cause obesity (moon face etc)?
not totally known
excess stimulation of food intake is likely
Any stress causes an increase in the secretion of ______ from the anterior pituitary, which causes secretion of cortisol
ACTH
Cortisol has a preferrential on amino acid mobilization. Explain.
cortisol usually does not mobilize the basic functional proteins of the cell, such as muscle contracile proteins and proteins of neurons
It will eventually mobilize these AAs, but not until all others have been used
What are the five stages of inflammation?
- Chemicals released from damaged tissue
- increased blood flow to area causes erythema
- capillary leakage followed by clotting of tissue fluid causes nonpitting edema
- infiltration of leukocytes
- fibrous tissue healing
What are the five anti-inflammatory effects of coritsol?
- Stabilizes lysosomal membrane, decreasing the amount of chemicals released
- Decreases permeability of capillaries (2/2 decreased proteolytic lysosome release)
- Decreased mediators means decreased WBC migration
- lymphocytes are suppressed
- reduces fever by preventing release of interluekin-1
The anti-inflammatory effects of cortisol boil down to two global effects:
stabilizing lysosomal membranes
reducing the formation of prostaglandins and leukotrienes from arachidonic acid in damaged cell membranes
What effect does cortisol have on lymph tissue?
causes significant atrophy, which decreases the output of T cells and antibodies from the lymphoid tissue
Describe the pathway for cortisol secretion:
- Corticotropin-releasing factor is released from the hypothalamus
- CRF triggers ACTH release from the anterior pituitary
- ACTH triggers cortisol release from the adrenal cortex
Describe the circadian rhythm of glucocorticoid secretion
the secretory rates of CRF, ACTH, and cortisol are high in the early morning and low in the late evening
When are glucocorticoids released?
Under stress conditions
Why do glucocorticoids decrease immune and inflammatory responses?
They decrease the natural killer cell activity
Block the synthesis of prostaglandins, thromboxanes, and leukotrienes
suppress the synthesis/secretion/action of chemical mediators (like histamine)
What are some of the most problematic side effects of glucocorticoid administration?
infection
poor wound healing
The adrenal medull functions as a sympathetic ______
ganglion, without postganglionic processes
Physiologic stress triggers release of adrenal catecholamines through ________
acetylcholine from preganglionic sympathetic fibers
Depolarizes chromaffin cells
depolarization sparks exocytosis of catecholamines
Secretion of adrenal catecholamines is triggered by:
- Sympathetic stimulation
- ACTH
- Glucocorticoids
What is the prevalence of impaired glucose tolerance/diabetes in adults over 65?
40-50%
Decline in beta cell function
The decline of GH and IGF with age is referred to as:
somatopause
leads to decreased muscle size and function
Why is hyponatremia a common finding in the elderly?
Changes in renal function and sensitivity
NOT due to changes in ADH
