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87 Cards in this Set
- Front
- Back
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Hormones of the anterior lobe of the pituitary
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GH
PRL ACTH FSH TSH LH |
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Propriomelanocrtin (POMC)
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ACTH
Melanocyte stimulating hormone (MSH) Beta-lipoprotin beta-endorphin |
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Growth hormone secr
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Pulsatile Secr
Incr by: sleep, exercise, puberty, starvation, hypoglycemia (+) GHRH (-) Somatostatin, somatomedin (IGF) |
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GH action
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decr glucose uptake
incr lipolysis incr prot synth, incr lean body mass incr IGF - rec is a tyr kinase IGF actions: 1. incr prot synth and linear growth 2. incr prot synth in muscle and incr lean body mass 3. incr organ size |
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PRL secr
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lactogenesis
Tonically inhibited by Dopamine (PIF) Stimulated by TRH NEG FDBK: via PRL mediated Dopamine rls |
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PRL -actions
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Breast development (with ER)
Lactation Inhibits ovulation: by decr synth and rls of GnRH inhibits GnRH actions on ant pit thus inhibiting FSH and LH and ANTAGONIZES them in the ovary Inhibits spermatogenesis by decr GnRH |
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PRL excess
cause sx tx |
Destruction of hypothalamus (loss of PIF) or prolactinoma
Galactorrhea Failure to ovulate Tx with bromocriptine (DA analogue) |
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Match to second messenger system
ACTH GnRH TRH glucagon oxytocin ADH (V1,V2) CRH MSH calcitonin TRH GHRH ATII HCG FSH TSH LH PTH |
IP3: CRH, TRH, GNRH, ATII, oxytocin, ADH (V1)
cAMP: ACTH, glucagon, ADH (V2) MSH, FSH, LH, Calcitonin, PTH |
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Tyr Kinase ligands
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Insulin
IGF |
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cGMP
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EDGF
ANP NO |
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ADH
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Supraoptic Nuclei
V2 - distal tubule for aqua porins V1 - constrict vasculature |
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Oxytocin
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paraventricular nuclei
milk ejection reflex dilation of cervix orgasm uterine contraction reduce post partum bleedin |
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Process of making thyroid hormone
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1. Iodide trapping of I- via iodide pump. Inhibited by thiocyanate, perchlorate anions, and high I-.
2. Peroxidation 2I- -> I2. Via peroxidase (inhibited by PTU) 3. Organification: Tyrosine incorporated in Thyroglobulin on follicular ribosomes 4. Tyr resides on thyroglobulin at follicular cell/lumen jx combine with I2 -> MIT + DIT 5. 2 DIT -> T4, DIT+MIT-> T3 6. Rls - stim from TSH- thyroglobulin rlsed. Excess DIT and MIT deiodinated by Thyroid deoidinase (def of this enzyme mimics I2 def) for recycling. Peroxidase also involved in peripheral conversion of T4 to T3 |
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TBG
hepatic failure pregnancy |
Hepatic failure - decr TBG-> incr free T3 and T4
Pregnancy: incr TBG -> decr free idodine. |
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Thyroid regulation
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T3 inhibits TRH receptors in pituitary.
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Thyroid actions
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CNS maturation in perinatal period-> MR if def
Bone growth in combination with GH and somatomedins acts like beta stimulation incr synthesis of N/K atpase-> incr O2 consumption catabolic effects |
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21 alpha hydroxylase def
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decr cortisol, aldosterone, deoxycorticosterone
Incr ACTH, androgens, virulization, HoTN |
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11 alpha hydroxylase def
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decr cortisol and aldo
incr deoxycorticosterone incr ACTH, androgens, virulization HTN |
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Cortisol regulation
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CRH found in paraventricular nuc
ACTH: upreg its own rec on adrenals Cortisol: inhibits CRH and ACTH rls |
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Dexamethasone suppresion test
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Potent glucocorticoid that can't cross bbb - thus tests pituitary suppression.
The test is given at low and high doses of Dexamethasone and the levels of cortisol are measured to obtain the results. A normal result is decrease in cortisol levels upon administration of low-dose dexamethasone. Results indicative of Cushing's disease involve no change in cortisol on low-dose dexamethasone, but inhibition of cortisol on high-dose dexamethasone. If the cortisol levels are unchanged by low and high-dose dexamethasone then a cortisol secreting adrenocortical tumor is highly suspect. |
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Cortisol actions
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stress hormone
stimu gluconeogenesis 1. incr protein catabolism 2. Decr glucose utilization and insulin sensitivity of adipose 3. Incr lipolysis for more glycerol to liver for gluconeogenesis. Antiinflamm: incr Lipocortin (inhibits PLPA2) Inhibit production of Il-2 and T cells. Maintenance of vasc sensitivity to catecholamines. |
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Addisons dz
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primary adrenocortical deficiency: AI destruction
Incr ACTH Decr glucocorticoids, Mineralcorticoids, androgens Sx: hypoglycemia (cortisol def), hyperpigmentation, decr pubic and axillary hair in women ECF vol contraction, HoTN, hyperkalemia, metabolic acidosis |
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Cushings Syndrome
cause sx Tx |
Syndrome: 1' adrenal prob or from exogenous steroid excess
Dz: overproduction of ACTh Hyperglycemia Incr androgens, cortisol Incr catabolism and muscle wasting poor wound healing Central obesity Virilization in women HTN, stiae Osteoporosis (incr cortisol) Tx: Ketoconazole (inhibits steroid synth), Metyrapone |
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Conn's syndrome
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Hyperaldosteronism
from ACTH secr tumor Hypokalemia Hypervolemia, HTN metabolic alkalosis DECR RENIN |
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21 beta hydroxylase def
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Adrenogenital syndrome
virilization in women incr ACTH decr Cortisol decr aldosterone Metabolic acidosis early puberty. Suppression of gonadal fx in both men and women |
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17 alpha hydroxylase def
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Decr androgens and glucocorticoids
Incr Aldo, incr ACTH lack of pubic hair and axillary hair on women hypoglycemia metabolic alkalosis, hypokalemia, HTN |
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Glut 2 rec
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glucose receptor on beta cells
glucose -> ATP which closes K+ channels in cell membrane leading to depol of beta cells opens Ca channels -> insulin secr Sulfonylureas do the same. |
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Insulin receptor
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tyr kinase -2alpha 2beta subunit
beta subunit has the tyr kinase autophos activity. Incr downreg its own rec Starvation= more rec Obesity= less rec |
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Glucogon
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incr gluconeogenesis: by decr production 2,6 bisphophate -which decr PFK activity
Incr lipolysis and urea production |
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Insulin and gluconeogenesis
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Insulin upregulates production of 2,6 bisphosphate - to incr action of PFK
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Insulin actions
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glycogenesis, glycolysis
Decr blood FA and ketoacid - stim fat deposition Incr AA uptake Stim K+ uptake into cells. |
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PTH actions
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kidny: incr phosphate dumping (incr urinary cAMP bc of PTH), incr Ca reabsorption
incr Ca reabsorption in intestine via conversion to 1,25 vit D in kidney |
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PTH origin
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Chief cells of parathryoid
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Albrights syndrome
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Pseudohypoparathyroid osteodystrophy
Defective Gs receptor in kidney and bone - rendering PTH ineffective Hypocalcemia, hyperphosphatemia elevated PTH |
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most common Cause of
hyperPTH hypoPTH |
hyperPTH most commonly due to PTH adenoma
HypoPTH most commonly due to thyroid surg. |
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CRF and PTH
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Decr GFR -> phosphate retention and incr serum Phos
-> incr complexing with Ca + Decr conversion to Vit D-> decr serum Ca -> Incr PTH = Renal osteodystrophy (incr bone resorption + osteomalacia) |
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1 alpha hydroxylase
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found in Kids
converts 25 vit D to 1,25 Upreg by decr serum Ca, incr PTH, decr serum phos |
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sun and vit D
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Sunlight takes 7 dehydrocholesterol to cholecalciferol - which is converted to 25 Vit D in the liver
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5 alpha reductase
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converts Testosterone to Dihydrotestosterone
Prostate finasteride is the inhibitor |
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Stimulation of cholesterol desmolase
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Incr by ACTH (adrenals)
Incr by LH (testiclees) |
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Inhibin
and Testosteron |
secr from Sertoli cells to inhibit FSH
testosterone inhibits secr of LH by inhibits GnRH rls and directtly on ant pit. |
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GnRH
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rls from arcuate nucleus of hypothalamus
stimulates FSH and LH rls from pit. Leuprolide is a GnRH analogue that initially bumps FSH and LH but then through fdbk lowers both. |
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FSH
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sertoli cells to maintain spermatogenesis which leads to inhibin rls
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LH
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acts on leydig cells for testosterone production
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Dihydrotestosterone
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Prenatal differentiation of external genitalia
male hair distrubution 5 alpha reductase is found in peripheral tissues - |
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Prenatal testosterone
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differntiation
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Puberty
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onset of pulsatile GnRH rls
FSH and LH are in turn rls in pulsatile fashion GnRH upreg its own rec in ant pit |
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FSH and LH lifetime levels
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prepubertal FSH>LH
pubertal/fertile period LH>FSH senescence FSH>LH |
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Theca Cells
Granulosa cells |
Theca cells produce testosterone via LH stim
Granulosa cells via aromatase convert local testosterone to 17beta estradiol (stim by FSH) |
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ER
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maturation and maintenance of fallopian tubes, uterus, cervix and vagina.
secondary sex characteristics breast development up regulates ER, LH, and PR rec prolif and development of granulosa cells. maintains preg stim PRL secr + blocks its actions on the breast |
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PR
fdbk involvement what does it do during cycle and preggar |
neg fdbk on FSH and LH during lacteal phase
maintains secretory activity of uterus during luteal phase maintains pregnancy helps breast devlopment' |
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Flutamide
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blocks DHT receptor good for BPH
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Double uterus, bicorneate nuc etc
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due to improper or incomplete fusion of the paramesonephric duct
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Sheehan syndrome
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Panhypopituitarism
Postpartum pit necrosis ischemia of the gland ass with hemorrhage and shock during childbirth Sx - #1 loss of gonadotrophin then subsequent loss of TSH and ACTH |
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Nelson syndrome
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After bilateral adrenal resection
Large pituitary adenomas due to lack of adrenal inhibition on prexisting pit microadenomas |
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Nodular goiter
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late stage of simple goiter
Most nodules are cold and thus do not take up radioactive iodine |
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Myxedema
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Hashimoto thyroiditis
Iodine def puffiness of face, eyelids and hands dry hair, hair loss, brittle hair slowed DTR |
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Cretinism
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iodine def, def enzymes, developmental def
Transplacental antithryoid abs transfer Sever MR darwfism and retarded bone development large tongue protuberant abdomen |
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Menorrhea
thyroid abnormalities |
Hypothyroid:
menorrhagia Hyperthyroid: amenorrhea, oligomenorrhea |
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Graves Dz
genetics |
HLA DR3, HLA B8 association
Thyroid stimulating Ig reacts with thyroid follicle TSH rec. |
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Struma Ovarii
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ovarian tumor made of thyroid tissue - hyperfxing
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Hashimoto thyroiditis
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antimicrosomal (antimitochondrial are primary biliary cirrhosis)
Slow indolent course euthyroid at first then hyperthyroid, then hypo Massive lymph infiltrate with GC in thryoid Atrophic Follicles and Hurthle Cells |
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Hashimoto abs
and genetics |
Autoantibodies
antithyroglobulin, antithyroid peroxidase, anti TSH rec, antiiodine rec. HLA-DR5, HLA-B5 incr incidence with pernicious anemia, DM, sjogrens |
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Subacute (de Quervain granulomatous) Thyroiditis
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Post viral - mumps/coxsackie
Focal destruction and granulomas Transient flulike illness and thyroid pain |
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Reidels
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thryoid tissue replaced with fibrosis
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Papillary Carcinoma
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Good prognosis, most common thyroid cancer
Ground galss orphan annie nuclei Psammoma bodies (calcified spheres), papillary projections into glandlike spaces Ass with prior radiotherapy |
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Follcular Carcinoma
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uniform follicles
poorer prognosis than papillary |
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Medullary Carcinoma of thyroid
pathophys associations |
C cells of thyroid
Makes calcitonin sheets of tumor cells with amyloid containing stroma Ass with MEN II a + b |
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Cause of Primary HyperPTH
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#1 parathyroid adenoma
#2 paraneoplastic syndrom Lung SCC and Renal CC #3 MEN I and MEN IIa |
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HyperPTH
sx |
Metastatic calcification in tiss, esp kids (nephrocalcinosi)
Incr Alk Phos Osteitis fibrosa cystica Renal calculi Peptic duodenal ulcer (hypercalcemia) |
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Causes of secondary hyperPTH
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CRF - vit D conversion impaired
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PseudohypoPTH
cause pathophys sx |
Mutation in GNAS1 - imprinting
Decr Ca, incr phos, incr PTH Multihorm resistance involving PTH and TSH, LH, FSH Kidney doesn't respond to PTH Shortened 4th and 5th metacarpals/tarsal, short stature etc |
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Primary vs Secondary hyperaldosteronism
renins levels causes |
Primary hyperaldo: Renin low
Secondary hyperaldo: renin high secondary to renal ischemia, tumors and edema (CHF, cirrhosis_ |
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Pheochromocytoma associations
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MEN IIa, IIb
NF vHL Tx - phenoxybenzamine, phentolamine |
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Neuroblastoma genetics
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N-myc
severity related to amount of amplified copies of the gene Homologous staining regions and double minutes Can differentiate in to ganglioneuroma HTN, catechols in urine large abdominal mass |
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DM1 genetic ass
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Pt mutation in HLA DQ
HLA DR4 + HLA DR5 less ass with familial than DM2 insulinitis |
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DM2
islets |
focal islet fibrosis and hyalinization
amylin deposition interfers with conversion of proinsulin to insulin or with sensing of insulin by beta cells |
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Secondary diabetes
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hemochromatosis
pancreatitis carcinoma of the pancreas GH excess Gluconoma Cushing acromegaly |
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MEN I
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Hyperplasia/tumor of:
Pituitary Parathyroid Pancreatic: Thus ZE syndrome, insulinomas, VIPomas Cr 11 - menin tumor supressor |
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MEN II a
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Ret oncogene mutation (tyr kinase)
Pheochromocytoma medullary carcinoma hyperPTH |
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MEN IIb
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ret mutation (tyr kinase)
pheo medullary carcinoma oral and intestinal ganglioneuromas/neuromas NO hyperPTH |
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Cause of juvenile diabetes
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Rubella mumps and coxsackie
can trigger and abs response to pancr beta cells. |
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Metformin
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decr hepatic gluconeogeneis
lactic acidosis is rare SE |
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Pioglitazone
Rosiglitazone |
insulin sensitization
can exacerbate CHF |
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Sulfonureas
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decr K+ efflux and incr Ca influx
incr pancreatic insulin rls can lead to hypoglycemia |
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Paragangliomas
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extraadrenal chromaffin cell tumors.
(tumors originating in the organ of zuckerland) |
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Granulosa-Theca tumor vs
Theca Fibroma vs Sertoli-Leydig cell tumor |
Granulosa-Theca tumor - lipid laden cells that secret ER - benign but leads to precocious puberty or endometrial hyperplasia
Theca fibroma: Meigs syndrome - ascites and hydrothorax Sertoli-Leydig - virilization - makes testosterone |
