endocrinology Flashcards
Thyroid development
Thyroid diverticulum arises from floor of primitive pharynx and descends into neck
Connected to tongue by thyroglossal duct, may perisist as cysts or the pyrimidal lobe of thyroid
ectopic thyroid tissue site is the tongue, removal may result in hypothyroidism if it is the only thyroid tissue present
Thyroglossal duct cyst presents as an anterior midline neck mass that moves with swallowing or protrussion of the tongue , thyroid follicular cells derived from endoderm
anterior pituitary
Anterior pituitary (adenohypophysis)
Secretes FSH, LH, ACTH, TSH, prolactin, GH, and B endorphin
Melantropin (MSH) secreted from intermediate lobe
Posterior pituitary…neurohypophysis
Stores and releases vasopressin (ADH) and oxytocin
both are made in the hypothalamus (supraoptic and paraventricular nuclei) and transported to posterior via neurohphysins (carrier proteins)
Derived from neuroectoderm
Adrenal cortex
GFR- G (ANG2 - mineralocorticoids, Aldosterone) ACTHCRH ( Glucocorticoids and Androgens
Medulla - chromaffin cells ( make catecholamines, epi NE)
ADH
increases water permeaability of distal convoluted tubule and collecting duct cells in the kidney to increase water reabsorption
increased plasma osmolality increases release, in SIADH ADH goes up even though plasma osmolality is decreased
CRH
increased ACTH MSH B-endorphins
decreased in chronic exogenous steroid use
Dopamine
decreases prolactin secretion
Makes TSH
prolactin-inhibiting factor Dopamine antagonists (antipsychotics) can cause galatorrhea due to hyperprolactinemia
GHRH and hrowth hormone
increases GH secretion
Analog is tesamorelin used to treat HIV associated lipodystrophy
Also called somatotropin, secreted by anterior pituitary
Stimulates linear growth and muscle mass through IGF1 (Somatomedin C) secretion by liver)) increases insluin resistence (you want resistence when growing
Released in pulses in response to GHRH, Secretion increases during exercise, deep sleep, puberty, hypoglycemia, CKD
Secretion decreased by glucose, Somatostatin, somatomedin (IGF1)
Excess secretion of GH (pituitary adenoma) may cause acromegaly or gigantism, treatment- somatostatin analogs (octreotide) or surgery
GnRH
increases FSH and LH release
Suppressed by hyperprolactinemia
Tonic GnRH analog (leuprolide) suppresses hypothalamic-pituitary gonadal axis
Pulsatile GnRH leads to puberty and fertility
MSH
increases melanogenesis by melanocytes
hyperpigmentation in Cushing disease, as MSH and ACTH share the same precursor molecule proopiomelanocortin
Oxytocin
Causes uterine contractions during labor
Responsible for milk let down reflext during sucking
Modulates fear, anxiety, social bonding, mood and depression
Prolactin
decreases GnRH
stimulates lactogenesis
pituitary prolactinoma–> amenorrhea, osteoporosis, hypogonadism, galactorrhea
Breastfeeding–> increased Prolactin–> decreased GNRH –> delayed postpartum ovulation
Somatostatin
decreases GH, TSH
GHinhibitinghormonee
Analogs used to treat acromegaly
TRH
increases TSH prolactin
Increased TRH (hyporthyroididsm
ADH vasopressin
synthesized in hypothalamus (supraoptic and paraventricular nuclei) stored and secreted by posterior pituitary
Regulates b1ood pressure (V1 receptors) and serum osmolality (V2 receptors)
Regulation of renal collecting duct aquaporins
ADH level is decreased in central DI, normal/increased in nephrogenic
Nephrogenic DI can be caused by mutation in V2 receptor
Desmopressin is the treatment for central DI and nocturnal enuresis (its an ADH analog)
Regulated by plasma osmolality, hypovolemia (ADH goes up)
Prolactin
Secreted mainly by Anterior pituitary
Stimulates milk production in breast
structually looks like growth hormone
Inhibits GnRH (affecting fertility)
inhibited by dopamine from tuberinfundibular tract of hypothalamus
Bromocriptine inhibits prolactin by stimulating prolactin secretion via being a dopamine agonist
Thyroid hormones
Thyroid produces T3 and T4, iodine containing hormones that control the body’s metabolic rate
Source: follicles of thyroid, 5’ deiodinase converts T4 (the major thyroid product) to T3 in peripheral tissue
(5,4,3)
Peripheral conversion is inhibited by glucocorticoids, B-blockers, propylthiouracil (PTU)
Reverse T3 (rT3) is a metabolically inactive byproduct of the peripheral conversion of T4 and its production is increased by growth hormone and glucocorticoids
T3 is increased by growth hormne and glucocorticoids
Functions of thyroid peroxidase include oxidation, orgarnification of iodine, and couplining of MIT and DIT. Inhibites by PTU and methimazole
Wolff-Chaikoff effect- excess iodine temporarilly turns off thyroid peroxidase (decreased T3, T4 production
Function of T3 (free, T3 binds nuclear receptor better than T4) 7Bs- brain maturation, Bone growth (synergism with GH), B-adrenergics, Basal metabolic rate increase, Blood sugar increases, Break down lipids (hyper lipidemia), stimulates surfactant synthesis in babies)
Parathyroid hormone
chief cells of parathyroid
Free Ca++ in blood, increased Ca and PO4 absorption in GI system, increased Ca and PO4 resorption
Increased CA reab from DCT
decreased PO4 reabsorption PCT
Increases 1a-hydroxylase in PCT (increased 1,25 OH2D (calcitriol D3)
PTH increases RANKL (receptor NF kB Ligand secreted by osteoblasts and osteocytes binds RANK r on osteoclasts–> increase Ca release
Decreased serum calcium, increased serum PO4, decreased serum Mg all INCREASE PTH
Very decreased MG will decrease PTH secretion
Ca homeostasis
Plasma Ca exists in 3 forms
ionized /free (45% in active form)
bound to albumin 40%
Bound to anions 15%
increased pH (less H+, less anealing) –> albumin binds more Ca–> decreased ionized Ca (cramps pain parasthesias, carpopedal spasm –>increased PTH
decreased pH (messes up albumin)–> binds less Ca - increased ionized CA–> decreased PTH
free Ca is the 1’ regulator of PTH changes in ph alter pth secretion, whereas changes in albumin dont
Calcitonin
Parafollicular cells (C cells of thyroid
decrease bone resorption of Ca
increase serum Ca –> increased Calcitonin secretion
Calcitonin opposes actions of PTH
Glucagon
Made by a cells of pancreas
Promotes glycogenolysis, gluconeogenesis, lipolyis, ketogenesis
Elevates blood sugar levers to maintain homeostasis when blood stream glucose levels fall too low
Secreted in response to hypoglycemia, inhibited by insulin, hyperglycemia, somatostatin
insulin
Preproinsulin (synthesized in RER of pancreatic B cells)–> cleavage of presignal –> proinsulin (stored in secretoryt granules–> cleavage of proinsulin–> exocytosis of insulin and C peptide
binds insulin tyrosine kinase–> induces glucose uptake (carrier-mediated transport) into insulin dependent tissue and gene transcription
increased glucose transport skeletal muscle and adipose tissue, glycogen synthesis and storage, TG synthesis, Na retention kidneys), protein synthesis (muscles), cell uptake of K and amino acids, decreases glucagon release, decreases lipolysis in adipose tissue
Insulin doesnt cross placenta (glucose does)
Glut 4 is insulin dependent (adipose tissue, striated muscle (excercise cn also increase GLUT 4)
Glut 1 (RBCs, brain, cornea, placenta)
Glut 2 (bidirectional B islet cells, liver, kidney, GIT (2 ways
Glut 3- brain and placenta
Glut 5- fructose in spermatocytes, GIT
Regulation of insulin
Glucose is major regulator of insulin release. increased insulin response
increased insulin response with oral vs IV glucose due to incretins (GLP1) and GIP
Glucose enters B cells–> increase ATP generated from glucose metabolism–> closes K channels –> depolarization of B cells –> Voltage gatesd Ca chennels open–> Ca influx–> stimulates insulin exocytosis
17 a hydroxylase deficiency
increased mineralocorticoids–> decreased K and increased BP
decreased cortisol, decreased Sex hormones
decreased androstenedione
XY- ambiguous genitalia, undescended testes
XX- lacks 2’ sexual development
21 hydroxylase deficiency
Most common
decreased mineralocorticoids (like taking spironolactone)
increased K, decreased BP, decreased Cortisol, increased sex hormones
increased renin, increased 17 hydroxy progesterone
Presents in infancy (salt wasting) or childhood precocious puberty
XX- virilization
11 B hydroxylase
decreased aldosterone, increased 11 deoxycorticosterone (increased BP)
decreased K BUT increased BP
decreased cortisol
increased Sex hormones
decreased renin activity
infants have hypertension, with precocious puberty
XX- virilization
Cortisol
increases Appetite, increase Blood pressure (upregulates a receptors on arterioles so increased sensitivity to NE and EPu, at high concentrations can bind to mineralocorticoids receptors, increased gluconeogenesis lipolysis, and proteolysis
decreased fibroblast activity (poor wound healing, decreased collagen synthesis, increased stria
decreased infalmmatory and immune responses (inhibits leukotrienes and PGs, inhibits WBC adhesion–> neutrophilia, blocks histamine release from mast cells, eosinopenia, lymphopenia, Blocks IL2 production
Decreases bone formation
Appetite regulation
Grelin- stimulates hunger (orexigenic effect) and GH release (via GH secretagog receptor)
Obese people have increased leptin due to increased adipose tissue, but decreased sensitivty to it
Sleep dep ==> leptin down regulates
Endocannabinoids–> increase appetite
