Endocrine Flashcards
which adrenergic receptors increase hepatic glucose output
beta 2 and 3
alpha 1 receptor works by which second messanger
IP3, Ca (Gq)
alpha 2 receptor works by which second messanger
Gi : decrease cAMP
beta1 receptor works by which second messanger
Gs increase cAMP
beta2 receptor works by which second messanger
Gs increase cAMP
alpha 1 prefers which adrenergic ligand
NE
alpha 2 prefers which adrenergic ligand
NE
which adrenergic receptor inhibits insulin release
alpha 2
beta 1 prefers which adrenergic ligand
NE=E
beta 2 prefers which adrenergic ligand
E
beta 3 prefers which adrenergic ligand
NE
where do you find beta 2 receptors
GI, urinary, adipose, liver, skeletal muscle, alpha cells in pancreas, bronchiole
where do you find beta 1 receptors
heart
where do you find alpha receptors
veins, lymph, beta cells in pancreas
beta3 receptor works by which second messanger
Gs increase cAMP
disease: high circulating catecholamines causing headache, palpitations, HTN, sweat, tachycardia
pheochromocytoma
disease: high cortisol, low ACTH
cushing syndrome (spontaneous or drug induced cortisol excess)
disease: high cortisol, high ACTH
cushing disease (pituitary adenoma)
how to distinguish cushing disease from syndrome
dexamethasone suppression test
osteoporosis, poor wound healing, virilization, HTN, round face, buffalo torso
cushing
treatment for cushings
ketoconozole, metyrapone
why do we get HTN with high cholesterol
alpha 1 stimulation causes vasoconstriction
disease: hypoglycemia, hypotension, hyperkalemia, acidosis, decreased hair and libido, hyperpigmentation
addisons
what will cortisol, CRH, ACTH look like in secondary adrenocortical insufficiency
low cortisol, high CRH, low ACTH
disease: primary adrenocortical insufficiency
addisons
why do we get hyper pigmentation with addisons
increased ACTH with alphaMSH can’t stimulate adrenal cortex (cuz its messed up) but the MSH produces discoloration
disease: primary hyperaldosteronism
conn syndrome
disease: hypervolemic, hypernatremic, HTN, low K, low H (alkalosis)
Conn syndrome
how do you treat conn syndrome
spironolactone (aldosterone antagonist)
disease: overproduction of mineral corticoids can occur when we have deficiency in which enzyme
17alpha hydroxylase
disease: cannot synthesize gluco or mineral corticoids so we get excess androgens leading to urinary ketosteroids and sterility
21 beta hydroxylase deficiency
a deficiency in which enzyme along the steroid hormone synthesis pathway would lead to HTN
11 beta hydroxylase
a deficiency in which enzyme along the steroid hormone synthesis pathway would lead to Hypotension
21 beta hydroxylase
angiotensin II stimulates what enzyme
aldosterone synthase
what regulates secretion of cholesterol desmolase
ACTH
what enzyme is needed to convert cortisol to the less active corticosterone after binding mineral corticoid receptors
beta hydroxysteroid dehydrogenase
who secretes PTH
chief cells
who secretes calcitonin
C parafollicular cells
oxytocin and ADH are stored in these enlarged axon terminals
herring bodies
glial cells of neurohypophysis
pituicytes
pineal gland secretory function is mediated by what type of receptor
beta adrenergic
what do F cells in pancreas secrete
pancreatic polypeptide
what do delta cells secrete in pancreas
somatostatin and gastrin
what do catecholamines and thyroid hormones have in common
derived from tyrosine (amine hormones)
POMC neurons make what kind of hormone
ACTH, MSH
what stimulates GH release
low glucose, GHRH, estrogen, testosterone, exercise, stress, sleep, alpha adrenergic agonist
Somatomedin C is also called
IGF1
GH directly affects what organs
skeletal muscle, adipose, liver
what does GnRH do
stimulates anterior pituitary to make LH and FSH
GH has indirect anabolic affect via what mediator
somatomedins made in liver
the hypothalamus releases what product that inhibits GH secretion from anterior pituitary
somatostatin
what test is performed to confirm diagnosis of GH excess (acromegaly)
administer oral glucose– should suppress GH levels and if they remain high we know there is exogenous GH secretion
how does prolactin suppress ovulation
inhibit GnRH
what stimulates prolactin release
TRH
what inhibits prolactin release
dopamine
3 sources of dopamine which inhibits release of prolactin
posterior pituitary, hypothalamus, non lactotroph cells of anterior pituitary
how does ADH increase peripheral resistance
binds V1 receptors increasing intracellular ca++ and contraction of SM in arterioles
disease: large volume of dilute urine excreted and high osmolarity of body fluids– fixed with ADH analogue
central DI
disease: large volume dilute urine excreted and high osmolarity of body fluids and high ADH
nephrogenic DI
MOA for nephrogenic DI
V2 defect
nephrogenic DI can occur secondary to what
lithium use, polycystic kidney disease, sickle cell anemia
how to treat nephrogenic DI
thiazide diuretics: inhibit Na reabsorb from PCT
disease: dilute body fluids, hyponatremia, high concentration of urine
SIADH
disease: enlargement of pituitary during pregnancy leads to infarction and hypopituitism
sheehan syndrome
what enzyme activates a GPCR by making the GDP GTP
GEF
what enzyme deactivates GPCR by hydrolyzing GTP
GAP
what are the ligands for RTKs
growth factors
inactive versus active form of insulin
hexamer: inactive
monomer: active
end result of RAS dependent insulin action
upreg glucokinase
end result of RAS independent insulin action
move GLUT4 to membrane (and activate glycogen synthase)
insulin resistance may happen because PKB does not activate to insert GLUT4 into PM’s. this could be because ___ gets phosphorylated at the wrong spot (ser/thr instead of tyr)
IRS1 and IRS2
epinephrine encourages what pancreatic secretion
glucagon (stress can cause DKA because E also inh insulin)
when we have no more glycogen, ___ stimulates gluconeogenesis
cortisol
estrogen binds ___ which is a HAT loosening DNA allowing transcription
SRC1
estrogen antagonists like ___ are going to activate HDAC to tighten chromatin
tamoxifen
conversion from T4 to T3 requires what enzyme
deiodinase
what enzyme hydrolyzes bonds to release MIT and DIT from TG allowing them to combine and form thyroid hormones
lysosomal proteases
MIT and DIT interact with ___ in the thyroid epithelial cell to produce tyrosine and thyroglobulin
intrathyroidal deiodinase
deficiency in intrathyroid deiodinase mimics what other condition
I- deficiency
who does I- get to lumen
pendrin + peroxidase
drug that blocks NIS
perchlorate and thiocynate
drug that blocks peroxidase
PTU
high levels of I- inhibit organification and synthesis of thyroid hormones (peroxidase aint working)
wolff chaikoff effect
what causes high TBG
pregnancy
thyroid hormone encourages synthesis of
NaK ATPase, beta adrenergic receptors, lysosome enzymes
to convert carotene to vitamine A we need what hormone
thyroid hormone
disease: antibodies destroy or block thyroid hormone synthesis by blocking peroxidase resulting in hypothyroid with goiter
autoimmune thyroiditis
disease: hypothyroidism in mother during pregnancy leads to this in baby
cretinism
disease: antibody stimulates TSH receptors
graves disease
disease: protruding eyeballs, periorbital edema, elevated thyroid hormone, goiter
graves
disease: impaired synthesis of thyroid hormones due to TG or TPO antibodies
hashimoto disease
disease: iodide deficiency in developing baby
cretinism
most common hyperthyroidism cause
graves
can you have goiter with i deficiency
yes- low T3/T4 stimulates TSH release
disease: new bones fail to mineralize so we get bending and softening
osteomalacia
disease: hyperreflexia, muscle twitching, tingling
hypocalcemia
disease: decrease QT interval, constipation, lack apetite, hyporeflexive, coma
hypercalcemia
academia leads to what ca++ related condition
H displaces Ca from albumin and you get increase in free ionized ca
chromic hypomagnesemia in alcoholics inhibits synthesis storage and secretion of what
PTH
how does vitamin D increase calcium reabsorption in GI tract
synthesis of calbindin which increases the absorptive capacity of GI epithelial cells so we can bring more into blood
how does PTH increase Pi excretion
inhibits NPT (NaPi cotrasport) in PCT
whats the job of osteoprotegrin
bone formation (inactivate osteoclast)
where does ca reabsorption take place in a kidney stimulated by PTH
TAL, distal tubule
what does estrogen do to [ca]
stimulate intestinal and renal absorbtion
what regulates activity of 1alpha hydroxylase
activated by PTH
inhibited by Ca
disease: stones, bones, groans
primary hyperparathyroidism
what are vitamin D levels like in someone with parathyroid adenoma
increased PTH causes lots of vitamin D activation so levels are HIGH
disease: renal failure or vitamin D deficiency leads to low ca
secondary hyperparathyroidism
in secondary hyperparathyroidism what are the Pi levels like
DEPENDS on the cause
vitamin D deficient: low Pi levels
renal failure: high Pi levels (cannot excrete)
disease: low ca, low vitamin D, high serum Pi, muscle cramping, seizure, poor tooth development, mental deficit, intestinal malabsorbtion
hypoparathyroidism
disease: autosomal dominant inherited, Gs of PTH-R is broken leading to hypocalcemia and hyperphosphatemia
pseudohypoparathyroidism
what do glucocorticoids do to [ca]
inhibit absorption from kidney and intestine
disease: high PTH, low vitamin D, low ca, high Pi
pseudohypoparathyroidism
disease: PTHrp
humoral hypercalcemia of malignancy
what are vitamin D levels in humoral hypercalcemia of malignancy
low (this is the only difference from hyperparathyroid symptoms)
how to treat humoral hypercalcemia of malignancy
furosimide (increase ca excretion)
etidronate (inhibit bone resorbtion)
disease: autosomal dominant mistake in CaSR
hypocalcuric hypercalcemia
disease: deficiency in 1alpha hydroxylase
rickets type I
disease: deficiency in vitamin D receptor
rickets type II
disease: bone mass decreases
osteoporosis
treat for osteoporosis
PTH, estrogen, calcitonin, RANKL inhibitor
treat for rickets/osteomalacia
vitamin D, ca, sunlight
what brings glucose into beta cell to initiate insulin release
GLUT2
high levels of ATP in pancreatic beta cell causes what to happen
K channels close (depolarization)
an increase in intracellular ___ causes clathrin coated vesicles containing insulin to be released from beta cell
Ca
drugs that promote closure of ATP dependent K channels to increase insulin secretions in T2D
sulfonurea (tolbutamide, glyburide)
which tissues require insulin for effective glucose uptake (via GLUT4)
muscle, adipose, liver
insulin activates SREBP1c for what purpose
uptake more LDL’s (to build more TAG’s not break them down)
what does insulin release do to blood [k]
decrease
disease: autoimmune destruction of beta cells
type I diabetes
disease: progressive exhaustion of beta cells leading to insulin resistance
type II diabetes
medication for type II diabetics that sensitizes them to insulin
metformin
disease: patient has antibodies to GAD65, IA2, insulin autoantibody
type i diabetes
disease: patient has antibody that is antagonist against insulin
type ii diabetes (blocks insulin at target tissue)
while auto Ab’s are found in type i diabetic patients, who is actually doing the most harm to beta cells
CTL’s
what is the most common genotype mutation in type i diabetes patients
HLA: DQ2 or DQ8
DR3 or DR4
if you have this genotype you are said to have “protective” factor from developing type i diabetes
HLA DR2 DQ6
what viruses can cause direct or indirect (via molecular mimicry) development of T1D
mumps, rubella, CMV
what bacteria can cause harm to beta cells
streptozocin, bafilomycin a1
cell markers for treg
CD4+25+FOXP3+
disease: messed up FOXP3
IPEX
what kind of cell infiltrates adipose tissue in obese patients causing inflammation and eventually leading to insulin resistance
M1 macrophages (TNFalpha and IL1beta)
excess palmitate induces expression of TLR4 in beta cells which will release cytokines to attract ___ which are cells that cause harm to these cells
M1 macrophages
what gets released (at normal term birth) in order to stimulate surfactant production in newborn babies– otherwise they get IRDS
glucocorticoids
enzyme that turns cortisol into cortisone so it doesn’t overstimulate mineral corticoid receptors
11 beta hydroxysteroid dehydrogenase
why does real licorice give us HTN
it blocks 11 beta hydroxysteroid dehydrogenase allowing mineral corticoids AND glucocorticoids to raise BP
how does cortisol suppress immune function
inhibit NFKB by sequestering it
reduce IL2 synthesis
promote T cell apoptosis
enzyme required to make estradiol in the ovaries
aromatase
estradiol that gets circulated to the brain has what effect
down regulation of FSH and LH
gives breath a fruity smell in T1D
acetoacetate
disease: headache, weakness, diarrhea, arrhythmia, increase HR, vomitting, SOB with kussmaul
DKA
disease: parathyroid, pituitary, pancreas tumors
MEN1
disease: L dopa decarboxylase deficiency
this is in APUD cells – MEN syndromes
most common parathyroid abnormality with MEN 1
hyper– hyperplasia of all 4 glands
most common pancreas abnormality with MEN 1
gastrinoma
most common pituitary abnormality with MEN 1
prolactinoma
whats RET
protooncogene– MEN2
whats menin protein
product of MEN1 gene (tumor suppressor)
disease: MTC and pheochromocytoma
MEN2
disease: MTC, pheochromocytoma, hyperparathyroidism
MEN 2a
what is unique to MEN2a
hyperparathyroid, cutaneous lichen amyloidosis
what is unique to MEN2b
mucosal neuroma, marfanoid habitus
disease: high E, high calcitonin, normal PTH
MEN 2b
