Adrenal Gland Flashcards
Adrenal Gland
Produce 4 principal hormones
u___
u___
u____(adrenaline)
u____(noradrenaline)
Composed of an inner medulla and outer cortex
uCortex derived from ____
uMedulla derived from ___ __ ___
Cortisol: Gluccocorticoid; increases glucose levels in the blood
Aldosterone: Mineralcorticoid: Increase excretion of _ and reabsorption of __
Epi/NE: Catecholamines. Released from medulla
Adrenal Gland
Produce 4 principal hormones
uCortisol
uAldosterone
uEpinephrine (adrenaline)
uNorepinephrine (noradrenaline)
Composed of an inner medulla and outer cortex
uCortex derived from mesoderm
uMedulla derived from neural crest cells
Cortisol: Gluccocorticoid; increases glucose levels in the blood
Aldosterone: Mineralcorticoid: Increase excretion of K and reabsorption of Na
Epi/NE: Catecholamines. Released from medulla
Adrenal gland sits above the kidney
It is surr by a __ __
Cortex has 3 layers
Glomerulosa (outer): releases aldosterone (mineralcorticoid)
Zona fasiculata secretes gluccocorticoid along with zona reticularis
Reticularis mostly but some of fasiculata secrete adrogens (DHEA and androstenedione)
Medulla: Sympathetic neurons synapse directly onto medulla. Medulla will behave like a postganglionic neuron
Adrenal gland sits above the kidney
It is surr by a fibrous capsule
Cortex has 3 layers
Glomerulosa (outer): releases aldosterone (mineralcorticoid)
Zona fasiculata secretes gluccocorticoid along with zona reticularis
Reticularis mostly but some of fasiculata secrete adrogens (DHEA and androstenedione)
Medulla: Sympathetic neurons synapse directly onto medulla. Medulla will behave like a postganglionic neuron
Adrenal Gland
Cortex
uCortisol (made in _____)
uAldosterone (made in _____)
u)____ steroids
Medulla
uEpinephrine
uNorepinephrine
u
Adrenal Gland
Cortex
uCortisol (made in fasiculata and reticularis layers)
uAldosterone (made in glomerulosa layer)
uAndrogenic steroids
Medulla
uEpinephrine
uNorepinephrine
u
Adrenal Medulla
Modified part of ___ nervous system
Primary stimulus for increased adrenomedullary secretion activation of sympathetic nervous system by___
Releases epinephrine and norepinephrine
uSecreted into blood by___ of __ __
uVary in their ____s for the different ___ receptor types
Epinephrine
uReinforces ____system in mounting general systemic “fight-or-flight” responses
uMaintenance of ___ __ __
____ blood glucose and blood fatty acids
If you have a patient who you administer pennicillin to
Problem: people can get an allergic reaction to this…most serious one is called anaphylaxis which can lead to shock
Give epi for anaphylaxis to maintain the arterial BP
If BP falls too low they get into shock and that’s it, kidneys will shut down and so forth
Adrenal Medulla
Modified part of sympathetic nervous system
Primary stimulus for increased adrenomedullary secretion activation of sympathetic nervous system by stress
Releases epinephrine and norepinephrine
uSecreted into blood by exocytosis of chromaffin granules
uVary in their affinities for the different adrenergic receptor types
Epinephrine
uReinforces sympathetic system in mounting general systemic “fight-or-flight” responses
uMaintenance of arterial blood pressure
uIncreases blood glucose and blood fatty acids
If you have a patient who you administer pennicillin to
Problem: people can get an allergic reaction to this…most serious one is called anaphylaxis which can lead to shock
Give epi for anaphylaxis to maintain the arterial BP
If BP falls too low they get into shock and that’s it, kidneys will shut down and so forth
Cells taken from a tumor of the adrenal medulla.-> _____
Chromaffin cells look round
If you add ___ ___ (required for nerves to be viable) they start to send out projections that form network as if they were neurons.
Cells taken from a tumor of the adrenal medulla.-> Pheochromocytoma
Chromaffin cells look round
If you add nerve GF (required for nerves to be viable) they start to send out projections that form network as if they were neurons.
Adrenal Gland
Cortisol
uCalled ____ as it ___ plasma glucose levels. Deficiency cause ____
Aldosterone
uCalled ____d as it promotes salt and water ___ in the kidneys
Adrenal Androgens
u—— and ——–(DHEA) are —–k male sex hormones
u
u
If you retain salt and water, that will ____ blood pressure
For people on steroids, High levels of steroid (glucocorticoids). These can bind to receptor for ____ too! Increase salt and water uptake and ___ BP. People who take these longterm… Make sure you monitor their BP
Adrenal Androgens
Don’t do much in males
Needed for puberty growth spurt in females
Adrenal Gland
Cortisol
uCalled glucocorticoid as it ↑ plasma glucose levels. Deficiency cause hypoglycemia
Aldosterone
uCalled mineralocorticoid as it promotes salt and water retention in the kidneys
Adrenal Androgens
uandrostenedione and dehydroepiandrosterone (DHEA) are weak male sex hormones
u
u
If you retain salt and water, that will increase blood pressure
For people on steroids, High levels of steroid (glucocorticoids). These can bind to receptor for aldosterone too! Increase salt and water uptake and raise BP. People who take these longterm… Make sure you monitor their BP
Adrenal Androgens
Don’t do much in males
Needed for puberty growth spurt in females
The adrenal cortex secretes steroid hormones (corticosteroids).
Glucocorticoids are ___ ____to insulin
Cortisol is the major glucocorticoid.
___ needed for function
____=Cortisol
Ones without 11-OH are inactive
The adrenal cortex secretes steroid hormones (corticosteroids).
Glucocorticoids are counter-regulatory to insulin
Cortisol is the major glucocorticoid.
11-OH needed for function
Hydrocortisone=Cortisol
Ones without 11-OH are inactive
Glucocorticoids
Cortisol is counter-regulatory to insulin
uCortisol ____ blood glucose and ____ gluconeogenesis
uCortisol inhibits peripheral __ ___ and stimulates the ____ of muscle protein. The amino acids are then available for liver ____
uCortisol induces the synthesis of ___ ___ in liver
uCortisol increases ___ ___ and __ ___ by the liver
u
Bc you aren’t making proteins from aa, those aa are exported to the liver and they enter gluconeogenesis
Just like GH stimulates gluconeogenesis, cortisol does the same thing. Upregulates the synthesis of the enzymes
Long term use of these ___ people to ____
Not everyone will get diabetes
Some people have a reserve in their kidney to produce sufficient insulin so they wont get diabetes
These are high pharmalogical doses that we are talking about
Glucocorticoids
Cortisol is counter-regulatory to insulin
uCortisol elevates blood glucose and promotes gluconeogenesis
uCortisol inhibits peripheral protein synthesis and stimulates the breakdown of muscle protein. The amino acids are then available for liver gluconeogenesis
uCortisol induces the synthesis of gluconeogenic enzymes in liver
uCortisol increases glycogen deposition and glucose release by the liver
u
Bc you aren’t making proteins from aa, those aa are exported to the liver and they enter gluconeogenesis
Just like GH stimulates gluconeogenesis, cortisol does the same thing. Upregulates the synthesis of the enzymes
Long term use of these predisposes people to diabetes
Not everyone will get diabetes
Some people have a reserve in their kidney to produce sufficient insulin so they wont get diabetes
These are high pharmalogical doses that we are talking about
Glucocorticoids
Cortisol is pleiotropic: it acts on __ ___
Increase Total __ __ __ count
Increase Resistance to ___
Increase Total body ___
Increase water ___
Increease___ activity
Decrease__ __ function
Decrease___
uHas ___ effects so allow other factors to __ __
u
For ___ to work optimally, cortisol needs to be present.
Cortisol is the main stress hormone that protects us from stress.
Epi is released in response to stress in the fight or flight reaction
They work together
It redistributes body fat.
Belly fat: due to cortisol
Fat gets deposited in the face.
That’s why people who take steroids get rounded, moon face
Depressive functions is why it is used for ___ ___
Knowing immune system is depressed, you should examine mouth carefully for candida (thrush) opportunistic infection.
Glucocorticoids
Cortisol is pleiotropic: it acts on many systems
ué Total white blood cell count
ué Resistance to stress
ué Total body fat
ué water excretion
ué brain activity
uê Immune system function
uê Inflammation
uHas permissive effects so allow other factors to work better
u
For epi to work optimally, cortisol needs to be present.
Cortisol is the main stress hormone that protects us from stress.
Epi is released in response to stress in the fight or flight reaction
They work together
It redistributes body fat.
Belly fat: due to cortisol
Fat gets deposited in the face.
That’s why people who take steroids get rounded, moon face
Depressive functions is why it is used for therapeutic effects
Knowing immune system is depressed, you should examine mouth carefully for candida (thrush) opportunistic infection.
Steroids inhibit enzyme: ____
Phospholipase A2 breaks down __ ___to ____ acids which can produce your ___
Prostaglandins protect the ____. Increase mucous, decrease acid secretion and they maintain blood flow.
High levels of cortisol and PLA2 is inhibited. Stomach: may develop ___
Steroids inhibit enzyme: PLA2
Phospholipase A2 breaks down membrane phospholipds to arachidonate acids which can produce your prostaglandin
Prostaglandins protect the stomach. Increase mucous, decrease acid secretion and they maintain blood flow.
High levels of cortisol and PLA2 is inhibited. Stomach: may develop ulcers
Physiologic Effects of Glucocorticoids
Antiinflammatory effects
u↓ ___and so ↓ ___ ___ from immune cells
uSuppress genes that code for ___ ___, ____ leading to ↓ __ ___proliferation
uStimulate production of___ (Annexin A1) which inhibits ___
FInhibit the two main products of inflammation, ___ and ____
•inhibits various leukocyte ___ ___ (epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst, etc.). Suppress ____ expression
u
u
NFKB is important in cytokine release
Physiologic Effects of Glucocorticoids
Antiinflammatory effects
u↓ NF-κB and so ↓ cytokine release from immune cells
uSuppress genes that code for IL1-6, 8, IFN-γ, leading to ↓ T-cell proliferation
uStimulate production of Lipocortin (Annexin A1) which inhibits PLA2
FInhibit the two main products of inflammation, prostaglandins and leukotrienes
•inhibits various leukocyte inflammatory events (epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst, etc.). Suppress cyclooxygenase expression
u
u
NFKB is important in cytokine release
Physiologic Effects of Glucocorticoids
Metabolic Effects
uInduce expression of enzymes involved in ____
uStimulation of gluconeogenesis from__ __ and ___
uInhibition of glucose uptake in ___ and ___ ___
uStimulation of lipolysis and proteolysis in __ ___tissue. ___ used for energy in muscle also induce insulin____
u
u
Physiologic Effects of Glucocorticoids
Metabolic Effects
uInduce expression of enzymes involved in gluconeogenesis
uStimulation of gluconeogenesis from amino acids and glycerol
uInhibition of glucose uptake in muscle and adipose tissue
uStimulation of lipolysis and proteolysis in extra-hepatic tissue. FA used for energy in muscle also induce insulin resistance
u
u
Physiologic Effects of Glucocorticoids
Development
uGC are required for promoting___ of the ___and production of ____ necessary for __ ___ lung function
Brain function
uGC important for formation of ___ associated with ___
uNeeded for___ and ___
mothers can be given glucocorticoids to treat the babies bc if babies don’t produce enough surfactant, they can’t breath properly
Excess can cause psychosis
Physiologic Effects of Glucocorticoids
Development
uGC are required for promoting maturation of the lung and production of surfactant necessary for extra-uterine lung function
Brain function
uGC important for formation of memories associated with emotion.
uNeeded for arousal and alertness
mothers can be given glucocorticoids to treat the babies bc if babies don’t produce enough surfactant, they can’t breath properly
Excess can cause psychosis
Adverse Effects of Glucocorticoids
nEndocrine
↓___secretion
↓___ ___ ___ release
nGI tract
n__ __
nBrain
nCNS ___, ___
nBone
n___bone formation ___bone mass, ____
nSkeletal muscle/CT
nProtein ____, muscle atrophy
nCollagen ____n, skin thinning
nImmune system
n___
n___
nGrowth
n)___ Linear growth
nCardiovascular/renal
n___ blood pressure
nSalt and water ___
nFat
nPromote ___ fat
nCarbohydrate
n___Gluconeogenesis
___ Free FA production
___ Insulin resistance
___ Hepatic glycogen deposition
Eye
n___, ___
These are alll physiological effects of glucocorticoids
GI inhibit prostaglandins
Cause osteoporosis
Collagen breakdown: Be very careful handling their gingiva. Gingiva is very thin
Increase BP bc of their action at mineralcorticoid receptor
Know this slide
Adverse Effects of Glucocorticoids
nEndocrine
↓GH secretion
↓TSH,LH,FSH release
nGI tract
nPeptic ulcers
nBrain
nCNS depression, psychosis
nBone
n↓bone formation ↓bone mass, osteoporosis
nSkeletal muscle/CT
nProtein catabolism, muscle atrophy
nCollagen breakdown, skin thinning
nImmune system
nImmunosuppression
nAntiinflammatory
nGrowth
n↓ Linear growth
nCardiovascular/renal
n↑blood pressure
nSalt and water retention
nFat
nPromote visceral fat
nCarbohydrate
n↑ Gluconeogenesis
n↑ Free FA production
n↑ Insulin resistance
n↑ Hepatic glycogen deposition
nEye
nCataract, glaucoma
These are alll physiological effects of glucocorticoids
GI inhibit prostaglandins
Cause osteoporosis
Collagen breakdown: Be very careful handling their gingiva. Gingiva is very thin
Increase BP bc of their action at mineralcorticoid receptor
Know this slide
Genomic action of glucocorticoids
Glucocorticoid has_____ receptors
Cortisol diffuses across them membrane
Binds receptor
Receptor dimerizes
Dimer complex undergoes Translocation to nucleus
Binds to dna GRE (___ __ __t)
Increases tx of certain genes
Some of these genes are those for enzymes of glucconeogenesis
Has genomic effects
There are some cell surface receptors but we haven’t really figured them out yet. Not important for exam.
Genomic action of glucocorticoids
Glucocorticoid has Intracellular receptors
Cortisol diffuses across them membrane
Binds receptor
Receptor dimerizes
Dimer complex undergoes Translocation to nucleus
Binds to dna GRE (Gluccocorticoid response element)
Increases tx of certain genes
Some of these genes are those for enzymes of glucconeogenesis
Has genomic effects
There are some cell surface receptors but we haven’t really figured them out yet. Not important for exam.
néBlood glucose
n Gluconeogenesis
n Brain activity
n Stress resistance
nêInflammation
n Immune response
n
Don’t need to know this figure
Just know that
All the steroid hormones are made from ____
Cholesterol comes from two sources
80% is made___
20% comes from the___
Figure is wrong
___ __ à Cholesterolà all the steroid hormones
Don’t need to know this figure
Just know that
All the steroid hormones are made from cholesterol
Cholesterol comes from two sources
80% is made endogenously
20% comes from the diet
Figure is wrong
Acetyl coAà Cholesterolà all the steroid hormones
Steroid hormone synthetic pathways
Committed step: ___ –> ____
Further pathways proceed from pregnenolone.
Committed step: cholesterol ® pregnenolone
Further pathways proceed from pregnenolone.
Steroid Hormone Biosynthesis
Mineralocorticoids
uA pathway from____ through ____ synthesizes the mineralocorticoids
uThis pathway resides in the outer layer (zona glomerulosa) of the adrenal cortex
uAldosterone is the physiologic mineralocorticoid in humans
uDeoxycorticosterone and aldosterone are __ ___ _____
Steroid Hormone Biosynthesis
Mineralocorticoids
uA pathway from pregnenolone through progesterone synthesizes the mineralocorticoids
uThis pathway resides in the outer layer (zona glomerulosa) of the adrenal cortex
uAldosterone is the physiologic mineralocorticoid in humans
uDeoxycorticosterone and aldosterone are 21-hydroxy-corticosteroids
Steroid Hormone Biosynthesis
Glucocorticoids
uA pathway through __ ____ ____ synthesizes ___
uThis pathway is in the middle layer of the adrenal cortex (zona fasciculata).
uCortisol is a __ ___ ___
Glucocorticoids
uA pathway through 17-hydroxy-progesterone synthesizes cortisol.
uThis pathway is in the middle layer of the adrenal cortex (zona fasciculata).
uCortisol is a 17-hydroxy-corticosteroid
Steroid Hormone Biosynthesis
Adrenal Androgens
uA ___ carbon side chain is___ from 17-hydroxysteroid precursors to synthesize the adrenal androgens
uThis occurs in the inner layer (zona reticularis).
uThe products are
dehydroepandrosterone
androstenedione
uThey are __ ____
Adrenal Androgens
uA two-carbon side chain is cleaved from 17-hydroxysteroid precursors to synthesize the adrenal androgens
uThis occurs in the inner layer (zona reticularis).
uThe products are
Fdehydroepandrosterone
Fandrostenedione
uThey are 17-ketosteroids
Androstenedione: ketone to OH
____ converts ___ to ___
Also converts androstenedione to estrone
All of these are estrogens
____ is major estrogen in the body in females
Aldosterone is only made in glomerulosa bc that is the only part that has the enzyme___ ___
Androstenedione: ketone to OH
Aromatase converts tetosterone to estradial
Also converts androstenedione to estrone
All of these are estrogens
Estradiol is major estrogen in the body in females
Aldosterone is only made in glomerulosa bc that is the only part that has the enzyme aldosterone synthase
Cortisol secretion is regulated by the hypothalamic-pituitary-adrenal system.’
Excess synthetic glucocorticoids
Those will feedback just like cortisol
Suppress ACTH
Leads to atrophy of adrenal cortex
After stopping steroids, Takes a long time to resume the production of cortisol
Weeks to a year
Cortisol secretion is regulated by the hypothalamic-pituitary-adrenal system.’
Excess synthetic glucocorticoids
Those will feedback just like cortisol
Suppress ACTH
Leads to atrophy of adrenal cortex
After stopping steroids, Takes a long time to resume the production of cortisol
Weeks to a year
Corticotrope:
CRH binds to ____r. Linked to ___
ACTH released
Moves to adrenal cortex
Bind to receptor
Also coupled to ___
Produce cortisol.
Written on next slide
Corticotrope:
CRH binds to receptor. Linked to AC.
ACTH released
Moves to adrenal cortex
Bind to receptor
Also coupled to cAMP
Produce cortisol.
Written on next slide
Regulation of Cortisol Secretion’
Steps
___ __ ___ secreted by the hypothalamus stimulates secretion of pituitary ___
uACTH stimulates the conversion of___ to ____ and thus to the synthesis and secretion of all the adrenal ____
uCortisol “feeds back” on the hypothalamus to reduce ___ secretion.
uACTH secretion undergoes ___ variation, peaking in __ __
u
u
u
Regulation of Cortisol Secretion’
Steps
uCorticotropin releasing hormone (CRH) secreted by the hypothalamus stimulates secretion of pituitary ACTH.
uACTH stimulates the conversion of cholesterol to pregnenolone and thus to the synthesis and secretion of all the adrenal corticosteroids.
uCortisol “feeds back” on the hypothalamus to reduce CRH secretion.
uACTH secretion undergoes diurnal variation, peaking in late sleep.
u
u
u
There is a peak in ACTH secretion during late sleep. This is a ___ variation.
n↑GC levels at ____ and peak at ___ am
ACTH rises first and then you have rise in cortisol
Cortisol rises to prepare us for the stresses of the day
Body knows that we are going to wake up soon and we need to be ready for the stresses of the day
Patients def in cortisol…You should schedule them early in the morning when there cortisol levels are highest
Opposite for people who work at night. Their rhythm is switched. Their levels are highest at night.
There is a peak in ACTH secretion during late sleep. This is a diurnal variation.
n↑GC levels at 3-4am and peak at 8am
ACTH rises first and then you have rise in cortisol
Cortisol rises to prepare us for the stresses of the day
Body knows that we are going to wake up soon and we need to be ready for the stresses of the day
Patients def in cortisol…You should schedule them early in the morning when there cortisol levels are highest
Opposite for people who work at night. Their rhythm is switched. Their levels are highest at night.
Adrenal Steroids
Transport
u___and ___ bind to ___ ___ ___(CBG) also called ___n and also to ___
uCBG has ___ affinity for cortisol but ___ capacity, whereas albumin has ___ affinity for cortisol but ___ capacity
uSince only unbound cortisol exert biologic activity, affinity and capacity of plasma proteins regulate the ___ and ___ of hormones
CBG has Low capacity to carry cortisol
___ is the major transport protein for cortisol
Other sex hormones can bind to ___
Adrenal Steroids
Transport
uCortisol and progesterone bind to corticosteroid‑binding globulin (CBG) also called transcortin and also to albumin
uCBG has high affinity for cortisol but low capacity, whereas albumin has low affinity for cortisol but high capacity
uSince only unbound cortisol exert biologic activity, affinity and capacity of plasma proteins regulate the availability and activity of hormones
u
CBG has Low capacity to carry cortisol
CBG is the major transport protein for cortisol
Other sex hormones can bind to albumin
Adrenal Steroids
Transport
uThe amount of transcortin in plasma is elevated by___ __ ___), and lowered by ___ disease, ___disease or __ __
uAldosterone in serum is mostly bound to ___. A small proportion is bound to ___
uDehydroepiandrosterone and androstenedione are mostly bound to ___
u
Transport
uThe amount of transcortin in plasma is elevated by female sex hormones (estrogens), and lowered by liver disease, amyloid disease or multiple myeloma
uAldosterone in serum is mostly bound to albumin. A small proportion is bound to transcortin
uDehydroepiandrosterone and androstenedione are mostly bound to albumin
u
Metabolism
___ and ___ are responsible for cortisol metabolism
uCortisol is r____ in the liver and conjugated to ___ ___and excreted in the___
uCortisol activity is regulated by ___ _____ _____
___ and __ __ contain 11β-hydroxysteroid dehydrogenase type I
___ __ ___ cells contain 11β-hydroxysteroid dehydrogenase type 2
F
11β-hydroxysteroid dehydrogenase
Present in the kidney
Two types
I: mainly found in the liver. It converts ___ to ___
II: Kidney. Converts ___ to ___
Why is that important?
Some people take Prednezone
Enzyme works on 11 OH position
Type I enzyme ___ ___ the OH group…makes it ___
2 __ __ __and makes it ___
Lots of cortisol in the kidney, can bind to receptors of aldosterone. We don’t want that so it is inactivated so alosterone is free to act in the kidney.
You want cortisol to fcn in the rest of the body. Take cortisone from where you don’t want it, send it to the liver. Type I transfers cortisone from kidney back to cortisol. Then that can act all around the body
You can give steroids to pregg ladies without affecting the babies
Type 2 enzyme is present in ___
Give mom prednazone which is inactive.
Goes to the liver. Type I enzyme converts it to prednizalone (active)
When Active form gets to placenta, the type 2 enzyme in placenta makes it ____ so that it doesn’t affect the baby
The liver is not fcnal in the fetus so type 1 enzyme doesn’t work
It will stay ___
Metabolism
uLiver and kidney are responsible for cortisol metabolism
uCortisol is reduced in the liver and conjugated to glucuronic acid and excreted in the kidney
uCortisol activity is regulated by 11β-hydroxysteroid dehydrogenase
FLiver and adipose tissue contain 11β-hydroxysteroid dehydrogenase type I
FKidney collecting duct cells contain 11β-hydroxysteroid dehydrogenase type 2
F
11β-hydroxysteroid dehydrogenase
Present in the kidney
Two types
I: mainly found in the liver. It converts cortisone to cortisol.
II: Kidney. Converts cortisol to cortisone
Why is that important?
Some people take Prednezone
Enzyme works on 11 OH position
Type I enzyme puts on the OH group…makes it active
2 takes it off and makes it inactive
Lots of cortisol in the kidney, can bind to receptors of aldosterone. We don’t want that so it is inactivated so alosterone is free to act in the kidney.
You want cortisol to fcn in the rest of the body. Take cortisone from where you don’t want it, send it to the liver. Type I transfers cortisone from kidney back to cortisol. Then that can act all around the body
You can give steroids to pregg ladies without affecting the babies
Type 2 enzyme is present in placenta
Give mom prednazone which is inactive.
Goes to the liver. Type I enzyme converts it to prednizalone (active)
When Active form gets to placenta, the type 2 enzyme in placenta makes it inactive so that it doesn’t affect the baby
The liver is not fcnal in the fetus so type 1 enzyme doesn’t work
It will stay inactive
Clearance of Cortisol
Metabolism continued,
uLiver 11β-hydroxysteroid dehydrogenase 1 (11 βHSD1) converts___ TO ____ reversibly
uThis allows cortisone to be used as treatment for ___ ___
uKidney 11 βHSD2 catalyze the irreversible conversion o ___ to ___
uRemoval of cortisol allows ____ to bind mineralocorticoid receptor (MR) without ___ from cortisol
u
u
Clearance of Cortisol
Metabolism continued,
uLiver 11β-hydroxysteroid dehydrogenase 1 (11 βHSD1) converts cortisol to inactive cortisone reversibly
uThis allows cortisone to be used as treatment for inflammatory disorders
uKidney 11 βHSD2 catalyze the irreversible conversion of cortisol to cortisone.
uRemoval of cortisol allows aldosterone to bind mineralocorticoid receptor (MR) without competition from cortisol
u
u
Steroid hormones are converted to inactive metabolites in ___ __ and by the ___
- They are converted to inactive ___ ____
- These are conjugated to ___ or ___ acids and excreted in the___
Steroid hormones are converted to inactive metabolites in peripheral tissues and by the liver.
- They are converted to inactive tetrahydro‑derivatives.
- These are conjugated to glucuronic or sulfuric acids and excreted in the urine.
Cushing Syndrome
Cushing Syndrome
Endogenous causes
Usually due to ___ ___ ___ , secondary to ACTH-secreting pituitary ___
Can be due to __ ___ or production of ___ from ectopic___ tumors
Exogenous causes
FLarge doses of ___ given for the management of, for example, asthma, rheumatoid arthritis, lupus, or chronic skin conditions can increase cortisol levels in the blood.
Cushing Syndrome
uEndogenous causes
FUsually due to bilateral adrenal hyperplasia, secondary to ACTH-secreting pituitary adenoma
FCan be due to adrenal tumors or production of ACTH from ectopic lung tumors
uExogenous causes
FLarge doses of steroids given for the management of, for example, asthma, rheumatoid arthritis, lupus, or chronic skin conditions can increase cortisol levels in the blood.
uSigns and Symptoms
___ ____ (abdomen, neck, face), round face, hypertension, loss of subcutaneous adipose tissue, ___, striae, ___glycemia, muscle ___, ___ wound healing, mental disorders
uTreatment
___ __ ___
In 2012, ______ was approved to control hyperglycemia in adult patients who are not good surgical candidates.
uSigns and Symptoms
FTruncal adiposity (abdomen, neck, face), round face, hypertension, loss of subcutaneous adipose tissue, bruising, striae, hyperglycemia, muscle wasting, poor wound healing, mental disorders
uTreatment
Fsurgery, radiation, or medication.
FIn 2012, mifepristone was approved to control hyperglycemia in adult patients who are not good sur-
Fgical candidates.
Addison Disease
Addison
FAdrenal i_____ mostly __
___glycemia, ___tension. ___kalemia, fatigue, muscle weakness, ___ mucous membrane patches and pigmentation around the mouth (due to ___ACTH binding to___ receptors)
___ adrenal ___
uDue to defects in __ __
uLack of 21β-hydroxylase activity
F↓cortisol ↑ACTH, gland becomes ____ and ↑precursors such as 17-hydroxyprogesterone that make ____s to cause virilization
FMetabolite ___ in ___ is ___
Addison
FAdrenal insufficiency mostly autoimmune
•Hypoglycemia, hypotension. Hyperkalemia, fatigue, muscle weakness, pigmented mucous membrane patches and pigmentation around the mouth (due to ↑ACTH binding to MSH receptors)
Congenital adrenal hyperplasia
uDue to defects in cortisol synthesis
uLack of 21β-hydroxylase activity
F↓cortisol ↑ACTH, gland becomes hyperplastic and ↑precursors such as 17-hydroxyprogesterone that make androgens to cause virilization
FMetabolite pregnanetriol in urine is diagnostic
Addison Disease
Congenital adrenal hyperplasia
uDefect in __ ___
FProduce __ _____
FHas mineralocorticoid activity so ____
Congenital adrenal hyperplasia
uDefect in 11-hydroxylation
FProduce excess deoxycorticosterone
FHas mineralocorticoid activity so hypertension
