Test 3: lecture 8 adrenal gland Flashcards
layers of the adrenal cortex
___ are made by adrenal cortex
corticosteroids such as
mineralocorticoid – aldosterone (by zona glomerulosa)
glucocorticoids (by zona fasciculata and zona reticularis)
cortisol
corticosterone
androgens (by zona fasciculata and zona reticularis)
___ are made in the zona glomerulosa
Corticosteroids by adrenal cortex
mineralocorticoid – aldosterone (by zona glomerulosa)
glucocorticoids (by zona fasciculata and zona reticularis)
cortisol
corticosterone
androgens (by zona fasciculata and zona reticularis)
___ are made by the zona fasciculata
Corticosteroids by adrenal cortex
mineralocorticoid – aldosterone (by zona glomerulosa)
most of the glucocorticoids (by zona fasciculata and zona reticularis)
cortisol, corticosterone
some of the androgens (by zona fasciculata and zona reticularis)
___ are made in the zona reticularis
Corticosteroids by adrenal cortex
some of the glucocorticoids (by zona fasciculata and zona reticularis)
cortisol
corticosterone
most of the androgens (by zona fasciculata and zona reticularis)
___ are made in the adrenal medulla
catecholamines
epinephrine
norepinephrine
___ are catecholamines made in the adrenal medulla
epinephrine
norepinephrine
cortisol and corticosterone are ___made where?
glucocorticoids (corticosteroids by the adrenal cortex) made in the zona reticularis and zona fasciculata
corticosteroids are made from ___ in the __
cholesterol
mitrochondria and ER
rate limiting step of synthesis of corticosteroids
cholesterol → pregnenolone
aldosterone formation does not use what enzyme
hydroxylase (this is used to make cortisol and androgen)
Cholesterol desmolase
also known as
P450scc CYP11A1
1st step and rate limiting step of cholesterol into catecholamines
17a-hydroxylase/17,20 lyase
also known as P450c17 CYP17
used to make cortisol and androgen
Aldosterone synthase
P450c11AS CYP11B2
used to make aldosterone
synthesis of corticosteroids occurs in
mitochondria and ER
results in release of cortisol
transport of cortisol hormone
75% bound to cortisol-binding globulin (transcortin)
15% to albumin,
10% free.
Half-life: 60-90 minutes
___: 50% bound to albumin. half life is 20 mins
aldosterone
50% bound to albumin,
10% to transcortin,
40% free.
Short half-life: 20 minutes
___ 75% is bound to transcortin with a 60-90 min half life
Cortisol
75% bound to cortisol-binding globulin (transcortin)
15% to albumin,
10% free.
Half-life: 60-90 minutes
why does aldosterone have a shorter half life then cortisol
40% of aldosterone is free (not bounded to protein)
can be broken down faster
___ is the most potent mineralcorticoid
aldosterone (90%)( made in the zona glomerulosa of the adrenal cortex)
what are some things other than aldosterone that can act as a mineralcorticoid?
Deoxycorticosterone (1/30 as potent, limited amount)
9a-fluorocortisol (synthetic, more potent)
Corticosterone (slight mineralocorticoid activity)- (type of glucocorticoid made mostly in the zona fasciculata)
Cortisol (slight, 10%)
Cortisone (synthetic, slight)
what is the major glucocorticoid
Cortisol (very potent, 95%)
Corticosterone (4%)
(type of glucocorticoid made mostly in the zona fasciculata, some made in the zona reticularis)
what are some synthetic glucocorticoids
Cortisone (as potent)
Prednisone (four times as potent)
Methylprednisone (five times as potent)
Dexamethasone (30 times as potent, specific)
what type of synthetic glucocorticoid does not have mineralocorticoid activity
Dexamethasone (30 times as potent, specific
aldosterone
mineralocorticoid – aldosterone (by zona glomerulosa)- adrenal cortex
responsible for Na+/K+ balance
sodium-retention hormone
stimulates excretion of K+ in the principal cells
stimulates excretion of H+ in the intercalated cells
most effect in the collecting tubules, less effect in the distal tubule and collecting duct
causes Na+ to be conserved and K+/H+ to be excreted
responsible for 90% of the mineralocorticoid effects
___ causes Na+ to be conserved and K+/H+ to be excreted
aldosterone
mineralocorticoid – aldosterone (by zona glomerulosa)- adrenal cortex
aldosterone stimulates the reabsorption of ___ in the ____
Na
kidneys, salivary and sweat glands
aldosterone stimulates the excretion of ___ in ___
K in the kidney, salivary and sweat glands
H in the kidney
mechanism of aldosterone
receptor in cytoplasm
leads to increase in Na/K ATPase (Na in/K out)
Na/H antiporters (Na in/H out)
sodium channels ( Na in)
increased ___in extracellular fluid → increases aldosterone secretion
K+
increased activity of the ____system → angiotensin II → increases aldosterone
renin-angiotensin
breakdown of aldosterone
conjugated to form glucuronic acid and sulfates
excreted in bile (25%), feces and urine (75%)
present in nanogram (10-9) levels (1000 times less than cortisol) (present in very low levels- but very potent)
Hypersecretion of aldosterone
Hypokalemia (low K+) –> muscle weakness
Alkalosis (more basic pH of blood, cause H are excreted)
Hypertension (increase in Na causes increased BP)
Hyposecretion of aldosterone
Hyperkalemia (too much K)–> cardiac toxicity
Acidosis (pH decreases, more H in the blood)
hypovolemia (sodium loss→ low BP → shock) -> death
____ is the stress hormone
cortisol
type of glucocorticoids (by zona fasciculata and zona reticularis) which is a corticosteroid made in the adrenal cortex)
___ is necessary to resist stress and inflammation
cortisol
type of glucocorticoids (by zona fasciculata and zona reticularis) which is a corticosteroid made in the adrenal cortex)
cortisol stimulates ___ by liver
gluconeogenesis
- Cortisol mobilizes amino acids from the extrahepatic tissues mainly from muscle
- Cortisol increases the enzymes required to convert amino acids into glucose in the liver
•Cortisol mobilizes ____ from the extrahepatic tissues mainly from muscle
amino acids
•Cortisol increases the enzymes required to convert amino acids into ___ in the liver
glucose
stimulation of gluconeogenesis by liver
cortisol has anti-___ effects causing a decrease in the use of cellular glucose
insulin
cortisol increases blood ___ and can lead to ____
glucose
adrenal diabetes
cortisol will cause the increase of proteins___ and the reduction of proteins ___
in the liver
in the muscles
increased blood amino acids (aa), increased aa transport into hepatic cells, but decreased aa transport into extrahepatic tissues
reduction in cellular proteins in all tissues except liver
increased liver and plasma proteins
enhanced mobilization of fatty acids from adipose tissue and utilization of free fatty acids for energy
cortisol enhanced mobilization of fatty acids from ___ and utilization of free fatty acids for energy
adipose tissue
cortisol will increase blood ___
glucose, amino acids and fatty acids
Inflammation Processes
____: release of chemical substances by damaged tissue.
•Red (erythema): increased blood flow.
____: leakage of capillaries.
•Fever
___ by leukocytes.
•Scar: ingrowth of fibrous tissue.
pain
- Edema
- Infiltration
anti-inflammatory effect of cortisol
- stabilizes lysosomal membranes- reduces tissue damage
- decreases permeability of capillaries- reduces edema
- decreases migration of white blood cells (WBCs) to inflamed areas
- suppresses the immune system, especially T lymphocytes
- lowers fever – reduces release of IL-1 from WBCs
- also causes resolution of inflammation
keeps inflammatory process under control
large doses of cortisol will have a ___ effect
immunosuppressive
- decreases the number of lymphocytes
- decreases the output of both T cells and antibodies
- prevents rejection of transplanted organs
why use large dose cortisol for transplanted organs
will suppress the immune system- suppress rejection
receptor for cortisol is ___
in the plasma
what is the DNA element that cortisol binds to
cortisol binds to receptor in the plasma, then the cortisol-receptor complex will go into nucleus and bind with the GRE (glucocorticoid response element)
regulation of cortisol secretion is by ___
Adrenocorticotropic hormone (ACTH) made by the anterior pituitary gland
(peptide hormone)
also called corticotropin
how does ACTH work
ACTH binds to melanocortin 2 receptor
activation of adenylyl cyclase
increased intracellular cAMP
conversion of free cholesterol to pregnenolone (1st step of coricosteroid production)
will eventually stimulate adrenal gland to make cortisol
____ is the receptor for ACTH
melanocortin 2 receptor
___ is the precursor to MSH and ACTH
POMC (proopiomelanocortin)
increased ACTH also means there is more ___ which leads to ___
MSH
skin pigmentation
both ACTH and MSH come form POMC
injection of angiotensin II will cause the expansion of ___
zona glomerulosa
an injection of ACTH would cause the expansion of ___
zona fasciculata
zona reticularis
HPA
cortisol deficiency would result in
high ACTH and increase in skin pigmentation cause there is more MSH (from same precursor -POMC)
cortisol not there to inhibit the production of ACTH
hyperadrenalism
cushing’s disease
- Pituitary tumor-
- Ectopic ACTH-secreting tumors- increased amount of ACTH
Adrenocortical tumors- decreased amount of cortisol
•Mitotane is used to treat adrenocortical tumors
hypoadrenaliam
addison’s disease
Mineralocorticoid deficiency
Glucocorticoid deficiency
Causes
idiopathic: autoimunne destruction of adrenal cortex.
sponataneous: infections, tumors, trauma
iatrogenic:(adrenal suppressive therapeutic agents)→Cytotoxic (mitotane)•Ketoconazole (blocks ACTH actions)
3 causes of addisons
hypoadrenalism
Causes
idiopathic: autoimunne destruction of adrenal cortex.
sponataneous: infections, tumors, trauma
iatrogenic:(adrenal suppressive therapeutic agents)→ •Cytotoxic (mitotane)•Ketoconazole (blocks ACTH actions)
mitotane is used to treat hyperadrenalsim- can go to far and cause hypo
what are made in the adrenal medulla
catecholamines → norepinephrine and epinephrine
catecholamines come from ___
tyrosine
sympathetic nervous system produces what type of catecholamines?
norephinephrine
why is the adrenal medulla redundant?
produces catecholamine- 80%epinephrine• 20% norepinephrine.
the sympathetic nervous system also creates norepinephrine, which can be used to make epinephrine
physiological effect of epi and norepinephrine
regulate activities of visceral organs
cause excitatory effects in some organs but inhibitory effects in others
increase force and rate of the heart
increases glycolysis in the muscle and liver
increases mental alertness
increases rate of blood coagulation
increases metabolic rate
increase blood flow to active muscles and liver concurrent with decreased blood flow to most organs such as GI tract and kidneys
increases BP
mechanism of epinephrine
binds to B and alpha receptors
very rapid response from G protein receptors
adrenal medulla is stimulated by
special preganglionic nerve (special) does not synapse in the celiac ganglion like the other sympathetics, just passes through
adrenal medulla cells originated from the same cells as ___ neurons.
post-ganglionic
sympathetic innervation causes immediate reaction in emergency situations (flight or fight)
Hyperadrenalism (Cushing’s disease) results from excess secretion of glucocorticoids from the adrenal glands. What would some clinical signs be?
Symptoms:
Moon face in humans. Mobilization of fat from the lower part of the body, with concomitant extra deposition of fat in the thoracic and upper abdominal regions, giving rise to a buffalo torso.
Increased blood glucose concentration – adrenal diabetes.
Protein depletion in muscles, bone, and lymphatic tissues: muscle weakness, suppressed immune system (death of infection), osteoporosis.
hypoadrenalism (Addison’s disease) results from hyposecretion of either glucocorticoids (glucocorticoid-deficient Addisonian) or glucocorticoids and mineralocorticoids (Addisonian). What would some clinical signs and clinicopathologic changes be? How would these two syndromes differ from each other?
Mineralocorticoid deficiency: hyperkalemia, acidosis, sodium loss → decreased blood volume → circulatory shock → death within a few days.
Glucocorticoid deficiency:
Failure to maintain blood glucose concentration, failure to mobilize fat and proteins, causing consuming weakness (lethargy).
Highly susceptible to the deleterious effects of stress. A mild infection can cause death.- immune system is suppressed
Increased melanin skin pigmentation, due to increased production of ACTH and MSH as a result of glucocorticoid deficiency.
