Endo - FA Anat/Phys p322 - 332 Flashcards
Most common ectopic thyroid tissue site?
thyroid tissue at base of tongue
Thyroglossal duct could persist as what structure?
as cysts or pyrimidal lobe of thyroid
normal remnant of thyroglossal duct?
foramen cecum
What is thyroglossal duct cyst? You must diff dx from?
anterior midline neck mass that moves with swallowing or protrusion of the tongue - (cystic dilation of of thyroglossal duct remnant)
Diff dx w. a lateral neck mass would be a persistent cervical sinus leading to pharyngeal cleft cyst
Thyroid follicular and parafollicular cells derived from?
endoderm
Layers of Adrenal Cortex? embryo origin
Glomerulosa, Fasciculata, Reticularis, from mesoderm
Cell type of adrenal medulla? origin?
chromaffin cells; neural crest
Primary regulatory control of Glomerulosa?
RAAS (not pituitary!!)
Secretory product of Glomerulosa?
Aldosterone (Mineralocorticoids) “Zona Aldosterona”
Primary regulatory control of Fasiculata and Reticularis?
ACTH, CRH
Secretory product of Fasiculata?
Cortisol (Glucocorticoids)
Secretory product of Reticularis?
Androgens
Adenohypophysis is of what embryo origin?
oral ectoderm
Neurohypophysis is of what embro origin?
Neuro ectoderm
Most common tumor of adrenal medulla in adults?
Pheochromocytomas
Most common adrenal medulla tumor in children?
Neuroblastoma
Pancreas cell types and products?
α = glucαgon (peripheral) β = insulin (central) δ = somatostatin (interspersed)
INC hCG seen in what disease?
Choriocarcinoma
Why do we see hyperpigmentation in tumors that produce inc ACTH?
ACTH and MSH are both from POMC, so with over production of ACTH, once also sees an increase of MSH, leading to inc melanin deposition
Alpha subunit of hormones in ant pit is common in which hormones?
TSH LH FSH, hCG - why with inc hCG we can see thyroid sx, it can act like TSH.
If trauma cuts stalk between hypothal and pit - which hormone will increase? why?
PRL - bc normally inhibited by Dopamine
If we always produce oxytocin, then why does oxytocin only cause uterine contraction and milk letdown at the end of pregnancy?
In fetal development, oxytocin of mother stays constant. Later in gestation, INC EXPRESSION of Oxytocin RECEPTORS of myometrium, inc sensitivity to oxytocin.
Give an example of permissive action of endocrine hormones?
Cortisol release leads to inc catecholamines and glucagon (glycogenolysis)
3 Migration failures of Endocrine? - explain
- Lingual Thyroid - failure of migration of thyroid tissue to its final location, thyroid can form at any part of thyroglossal duct 2. Kallman syndrome - failure of GnRH secreting hormomes to migrate from olfactory lobes –> HT 3. Cryptorchidism - failure of testes to migrate to scrotum
Failure of apoptosis leading to endocrine disorder?
T1DB, inappropriate apoptosis of pancreatic Beta cells
Beta subunit of ant pituitary determines what?
hormone Specificity
Vasopressin made in what part of the brain? (which nucleus)
SupraOptic nuclei (some Paraventricular)
Oxytocin is made in what part of the brain?
Paraventricular nuclei (some Supraoptic)
Synthesis of Insulin occurs where?
rER
What transporter is needed to take glucose into insulin dependent cells?
GLUT 4
List all functions of insulin
Dec lipolysis in adipose tissue
Inc glucose transport in sk musc and adipose tissue
inc glycogen synthesis and storage
inc TAG synthesis
Inc Na retention - kidney
Inc protein synthesis
Inc cellular uptake of K and amino acids
Dec glucagon release
Does Insulin cross the placenta?
No, only Glucose does
List all glucose transporters and where they are? Which is insulin dependent and independent?
Dependent GLUT 4 - adipose, sk musc
Independent
GLUT 1 - RBC, brain, cornea, placenta
GLUT 2 - bidirectional - B islet cells, liver, kidney, small intestine. —- NOTE REGULATORS OF INSULIN
GLUT 3 - brain, placenta
GLUT 5 (fructose) - spermatocytes, GI tract
SGLT1/2 - Na/glucose transporters - kidney, SI
Can RBC use ketones for energy ?
No, they can only do anaerobic glycolysis, since they lack mitochondria. Therefore, can only use glucose
Why is there an increased response to oral glucose over IV
Due to incretins like GLP2 and GIP, which are released in response to meals and inc B cell sensitivity to glucose
Autonomic receptor regulation of insulin
. Release dec by α2, inc by β2 stimulation (2 = regulates insulin)
MOA of sulfonylureas?
block K channel, leading to depol of B cells membran –> causing influx Ca2+ thru voltage gated calcium channels, inc Insulin release
What is increased before closing of K+ channels in beta cells of pancreas due to the entrance of glucose?
Inc ATP/ADP ratio
Fxn of Glucagon?
(+) glycogenolysis, gluconeogenesis, lipolysis and ketone production
increase blood sugar levels - When your glucose is gone…Glucagon
What 3 things inhibit glucagon?
Insulin, Hyperglycemia, Somatostatin
Fxn of ADH
Inc water permeability of DCT and coll duct, to inc water resorption
What stimulates ADH release - except when?
inc plasma osmolality, except in SIADH, where osmo is low, and ADH is still secreted.
CRH (+) release of?
ACTH, MSH, β-endorphin
Dopamine antagonists, like antipsychotics, cause _______ bc of inc PRL?
Galactorrhea
What GHRH analogue drug used to treat HIV assoc lipodystrophy?
Tesamorelin
High levels of prolactin suppresses what?
GnRH
Pulsatile GnRH leads to?
puberty, fertility
4 symptoms of pituitary Prolactinoma?
Amenorrhea, Osteoporosis, Hypogonadism, Galactorrhea
Analogue of somatostatin used to treat acromegaly and esoph varices?
Octreotide
Two GLP analogues?
Exenatide, Liraglutide
Fxn of PRL?
Stimulates milk production in breast, Inhibits ovulation in females and spermatogenesis in males by (-) GnRH synthesis and release
How does PRL inhibit its own secretion?
PRL (-) its own secretion by inc dopamine synthesis and secretion from HT
Rx for PRL-oma?
Dopamine agonists like Bromocriptine, Pergolide (-) PRL secretion
Which Rx stimulate PRL secretion?
Dopamine antagonists (most antipsychotics) and estrogens (OCPs, pregnancy) stimulate PRL secretion
Most common cause of gastroenteritis in developed countries?
Norovirus (single stranded RNA virus)
What are the functions of growth hormone?
Stimulates linear growth Stimulates muscle mass
Increases insulin resistance (diabetogenic)
Growth hormone stimulates muscle mass through
IGF-1 (Somatomedin C)
Secretion of GH inc/dec when?
Secretion INC during exercise, deep sleep, puberty, hypoglycemia.
Secretion inhibited by glucose, somatostatin, and somatomedin
function of ghrelin
Stimulates hunger (orexigenic effect) release of GH via GH secretagog receptor
ghrelin is released by
the stomach
ghrelin is increased in what two conditions
increased with sleep deprivation & prader willi syndrome
leptin is
satiety hormone
leptin is secreted by
adipose tissue
mutation in what gene causes congenital obesity
Mutation in leptin gene
Endocannabinoid receptors are in what part of the brain?
hypothalamus, nucleus accumbens
what stimulates cortical reward center and increase desire for high fat foods
endocannabinoids
Which receptors sense/regulates serum osmolarity and blood pressure
V1 recp - BP
V2 - serum osmolality
ADH is synthesized in the
supraoptic nucleus of the hypothalamus
ADH levels in central DBI or nephrogenic DI
dec in central diabetes insipidus
normal/Inc nephrogenic DI
Calcitonin opposes the action of
PTH
Calcitonin blocks what type of bone cell
osteoclast
Zona fasciculata produces
glucocorticoids
zona reticularis produces
androgens
zona glomerulosa produces
mineralocorticoids
ACTH stimulates what enzyme
cholesterol desmolase
cholesterol desmolase is inhibited by
ketoconazole
cholesterol desmolase converts cholesterol to
pregnenolone
what are the 2 roles of 17 alpha hydroxylase
converting pregnenolone to 17-hydroxypregnenolone and then to DHEA (Dehydroepiandrosterone)
converting prosgesterone to 17-hyrdroxyprogesterone and then to Androstenedione
2 drugs that block aromatase
Anastrozole and exemestane letrozole
what block 5 alpha reductase
finasteride
symptoms of 17 alpha hydroxylase in XY/XX
XY - ambiguous genitalia, undescended testes XX - lacks secondary sexual development
what blocks conversion of cortisol to cortisone?
Glycyrrhetininc Acid (AKA Enoxolone)
What stimulates aldosterone synthase?
Angiotensin II
what enzyme deficiency is associated with decreased renin?
11 Beta Hydroxylase
what enzyme deficiency is associated with increased renin and increased levels of 17-hydroxy-progesterone
21-hydroxylase
what is the level of renin and aldosterone in 17 alpha hydroxylase def?
low renin, high aldo
is the potassium level high or low in in 17 alpha hydroxylase def
low
what explains low serum K+ in 17 alpha hydroxylase def?
11 deoxycorticosterone acts similiar to aldosterone leading to hypokalemia and metabolic acidosis
which congenital adrenal enzyme def mimics Addison’s disease?
21 hydroxylase deficiency (b/c of high ACTH and low cortisol, hyperkalemia)
Which congenital adrenal hyperplasia has higher levels of sex hormones?
11β-hydroxylase def and 21 hydroxylase
which congenital adrenal enzyme def mimics Conn’s syndrome?
both 17 alpha hydroxylase and 11 beta hydroxylase def (b/c of low renin activity, hypokalemia due to high 11 DOC)
how is cortisol regulated?
CRH from the hypothalamus stimulates ACTH release from the pituitary that stimulates cortical production in the adrenal zona fasciculata
Actions of Cortisol
Inc appetite
Inc blood pressure
Inc insulin resistance & with that, dec glucose utilization (Inc gluconeogenesis, lipolysis, proteolysis)
dec fibroblast activity
dec bone formation (dec osteoblast activity)
Dec inflammatory and immune response
How does cortisol dec inflammatory/ immune response?
Inhibits production of leukotrienes and prostaglandins
Inhibits WBC adhesion
neutrophilia
Blocks histamine release from mast cells
Eosinopenia, lymphopenia
Blocks IL-2 production
describe the effect of excess cortisol on CRH, ACTH
decrease CRH, decrease ACTH
what property of cortisol can lead to purple striae
decreased fibroblast activity
`Exogenous corticosteroids can lead to what infection and why?
Exogenous corticosteroids can cause reactivation of TB and candidiasis (blocks IL-2 production).
2 reasons cortisol increases blood pressure
upregulates alpha 1 receptors on arterioles -> increased sensitivity to norepi and epi at high concentration, can bind to aldosterone receptor
cortisol decreases bone formation by decreasing what cell activity?
osteoblast
what acid/base disturbance can lead to hypocalcemia?
alkalosis (inc pH) –> inc affinity of albumin to bind Ca2+, leading to hypocalcemia
symptoms of hypocalcemia?
cramps, pains, paresthesias, carpopedal spasm
pH effect on PTH
Inc pH –> Inc PTH
dec pH –> albumin binds less Ca2+ –> Inc ionized Ca2+ –> dec PTH
How does Ca levels, pH, and albumin affect PTH?
Ionized/free Ca2+ is 1° regulator of PTH; changes in pH alter PTH secretion, whereas changes in albumin concentration do not.
name 4 functions of parathyroid hormone
- inc bone resorption of Ca2+ and PO43-
- inc kidney reabsorption of Ca2+ in distal convoluted tubule
- dec reabsorption of PO43- in proximal convoluted tubule
- inc 1, 25 (OH)2D3 (calcitriol) production by stimulating kidney 1 alpha hydroxylase in proximal convoluted tubule
explain how PTH leads to the activation of osteoclast which leads to inc serum Ca2+
inc production of macrophage colony-stimulating factor and RANK-L (receptor activator of NF-KB ligand)
RANK-L (ligand) is secreted by
osteoblast and osteocytes
RANK receptor is on what cell
osteoclasts and their precursors
how does RANK-L and RANK interact to stimulate Ca2+ release?
RANK-L (ligand) secreted by osteoblasts and osteocytes binds RANK (receptor) on osteoclasts and their precursors to stimulate osteoclasts and inc Ca2+ –> bone resorption
will low serum Mg2+ stimulate or inhibit PTH secretion? what about very low serum Mg2+?
low serum Mg2+ will stimulate, however very low Mg2+ will lower PTH
name 4 common causes of low serum Mg2+, thus can cause hyperparathyroidism
1)diarrhea 2)aminoglycosides 3)diuretics 4)alcohol
`Calcitonin action
Calcitonin opposes actions of PTH. Not important in normal Ca2+ homeostasis.
Calcitonin tones down serum Ca2+ levels and keeps it in bones
Fxn of Calcitonin and regulation
dec bone resorption of Ca2+
inc serum Ca2+ –> calcitonin secretion
T3 functions
Brain maturation
Bone growth
β-adrenergic effects
Basal metabolic rate
Blood sugar
Break down lipids
When are levels of TBG dec?
In hepatic failure, steroid usage, nephrotic syndrome
How does T3 T4 inc BMR?
via inc Na+/K+-ATPase activity –> incr O2 consumption, RR, body temperature
When are the TBG levels inc?
in pregnancy or OCP use (estrogen inc TBG)
Which adrenergic receptors does T3/T4 affect?
incr β1 receptors in heart = incr CO, HR, SV, contractility
What effect does T3/T4 have on glycogen and lipids?
inc glycogenolysis, gluconeogenesis, lipolysis
T4 is converted to T3 in peripheral tissue by which enzyme?
5’ deiodinase
T or F? Propylthiouracil inhibits only peroxidase.
F. inhibits both peroxidase and 5’-deiodinase
Explain the Wolff-Chaikoff effect
excess iodine temporarily inhibits thyroid peroxidase–> decr iodine organification–> decr T3/T4 production.
Methimazole inhibits?
thyroid peroxidase
coupling of monoiodotyrosine and di-iodotyrosine happens via which enzyme?
thyroid peroxidase
Which Anions inhibit iodine oxidation?
perchlorate, pertechnetate, thiocyanate, iodide
name all the hormones that use cAMP
FLAT ChAMP FSH LH ACTH TSH CRH hCG ADH (V2 receptor) MSH PTH calcitonin GHRH glucagon
name all the hormones that use cGMP
ANP, BNP, NO
name all the hormones that use IP3
GOAT HAG GnRH Oxytocin ADH TRH Histamine Angiotensin II Gastrin
Which hormones use intracellular receptor?
Progesterone, Estrogen, Testosterone, Cortisol, Aldosterone, T3/T4, Vitamin D
name all the hormones that use non Receptor-associated tyrosine kinase
which pathway?
Prolactin, Immunomodulators (eg, cytokines IL-2, IL-6, IFN), GH, G-CSF, Erythropoietin, Thrombopoietin
JAK/STAT pathway - think acidophils, cytokines
name all the hormones that use Receptor-associated tyrosine kinase - which pathway?
Insulin, IGF-1, FGF, PDGF, EGF
MAP kinase pathway
what 2 conditions increase SHBG in women?
OCPs, pregnancy (b/c estrogen inc SHBG synthesis)
What form of vitamin D is from plants?
vitamin D2
What form of vitamin D is from sun exposure?
vitamin d3
2 functions of Vitamin D
- inc absorption of dietary Ca2+ and PO43- 2. inc bone resorption –> inc Ca2+ and PO43- absorption
what 2 conditions increase SHBG in women?
OCPs, pregnancy (b/c estrogen inc SHBG synthesis)
