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154 Cards in this Set
- Front
- Back
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The hypothalamus is derived from what
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Alar plates of the diencephalon (part of the neural tube)
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The adenohypophysis is derived from what
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oral cavity ectoderm
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What is Rathke's pouch
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An evaginated thickening of oral cavity ectoderm that becomes the adenohypophysis
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The pineal gland does what (normally)
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Produces melatonin
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The pineal gland develops from what
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Dorsal growth from roof of diencephalon
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Describe the formation of the thyroid gland
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Grows downward from the foramed cecum as the thyroglossal duct and settles and develops anterior to trachea
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Congenital hypothyroidism can be caused by a deficiency of what
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Iodine
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Congenital hypothyroidism has what presentation
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Cretinism:
Severe mental retardation and physical abnormalities |
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The parathyroid glands develop from what
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The 3rd and 4th pharyngeal pouches (endoderm)
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22q deletion is associated with what
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DiGeorge Syndrome
- Altered migration of neural crest cells = CATCH22 |
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What is CATCH 22
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Symptoms of DiGeorge Syndrome:
Cardiac abnormality Abnormal facies Thymic aplasia Cleft palate Hypocalcemia/parathyroidism |
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Describe the development of the adrenal glands
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Cortex - From lateral plate mesoderm
Medulla - From neural crest cells (chromaffin cells) |
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Congenital adrenal hyperplasia causes what
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Block in production of cortisol and aldosterone causes increased androgen production:
Masculinization menstrual irregularities, poor fertility in females precocious puberty in males |
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The pancreas is derived from what
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Foregut endoderm
Buds off from primitive pancreatic ducts |
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What are the cell types in the anterior pituitary
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Somatotroph
Lactotroph Cortictroph Thyrotroph Gonadotroph |
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What hormones are secreted by the anterior pituitary
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GH
PRL POMC (ACTH, lipotropins, endorphins) TSH LH FSH |
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What are the actions of growth hormone
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Mainly increases protein synthesis
Also saves glucose for the nervous system IGH production and release from hepatocytes Decrease blood AA levels Decrease BUN (Positive nitrogen balance) Increase DNA, RNA, and protein synthesis Decrease RQ (More fat utilization) Somatic growth Growth and calcification of cartilage |
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At high concentrations, GH can cause
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insulin resistance
Gigantism before puberty Acromegaly after puberty |
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What are the stimulators for the release of GH
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hypoglycemia
Ghrelin Alpha adrenergic stimulation Stage III and IV sleep |
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What is the main action of IGF
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Increased DNA synthesis and cell division
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IGF-1 deficiency results in what? IGF-2?
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IGF -1: Intrauterine growth deficiency and postnatal growth retardation
IGF-2: Intrauterine growth retardation |
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What are the major inhibitors and stimulators of PRL release
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(-) - Dopamine
(+) - TRH/VIP/OT, Stress, estrogen, hypothermia, vaginal or nipple stimulation |
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What are the main actions of PRL
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INHIBITION OF GnRH
Mammary gland development Milk production in primed breast Ovarian and adrenal effects Immune modulation Stim. of maternal behaviors TK linked receptors and intranuclear receptors |
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What would happen to the PRL levels if there were to be detachment of the pituitary gland
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PRL would greatly increase due to loss of tonic dopamine inhibition
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What are the symptoms of a PRL hypersecretion state
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Block of GnRH causing infertility/menstrual irregularity (LH interference) and impotence/loss of libido in men (decreased testosterone)
Galactorrhea If PRL tumor growth is occuring could block vessels, compress optic chiasm, and compress hypothalamus |
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What are some pharmacologic treatments for PRL hypersecretion
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D2 receptor activation!
Bromocriptene (older, daily dosage) Cabergoline (new, 2x week dosage) |
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What is/are the action(s) of ACTH
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Stimulation of adrenal cortex to release corticoids
- Stimulates StAR (Steroidogenic Acute Regulatory) protein production which preps cholesterol for androgen production along with 20,22 desmolase |
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What are the main inhibitory and stimulatory factors for ACTH release
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Stim - *Stress*, hypothermia, hypoglycemia, pyrogens, epi
Inhibition - Cortisol |
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During excessive production of POMC/ACTH what happens
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ACTH is broken down into alpha-MSH which stimulates melanocytes
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Hypersecretion of ACTH results in what situation? Hyposecretion?
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Hypersecretion --> Cushing's Syndrome
Hyposecretion --> Addison's Disease |
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How is TSH released
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In a circadian pattern peaking at night and lowest in the early evening
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What is the action of TSH
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Stimulate release of T3 and T4 from thyroid
Stimulation of iodide transport into thyroid Stimulation of production of thyroglobulin |
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What are the major stimulatory and inhibitory factorys for TSH
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Stim - TRH
Inhibition - Mainly T3 |
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What are the actions of LH in females and males
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Females - Stimulation of follicular growth and rupture (ovulation), thecal cell androgen production, luteotropic (estrogen and progesterone secretion)
Males - Stimulate testosterone production in Leydig cells |
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What are the actions of FSH in females and males
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Females - Prepare next round of follicles, Stimulate aromatase in granulosa cells, synergize with estrogen to induce LH receptors on granulosa cells leading to ovulation
Males - Stimulate spermatogenesis by sertoli cells, induce LH receptors on Leydig cells --> increased testosterone |
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FSH and LH release is stimulated and inhibited by what
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Stim - GnRH, Rapidly rising estrogen
Inhibition - Normal estrogen, inhibin (for FSH) |
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Describe the conversion of Cholesterol into Testosterone, Progesterone, and Estrogen (Estradiol and Estrone) in thecal and granulosa cells
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Thecal cells:
Cholesterol to pregnenolone via SCC Pregnenolone to Progesterone via 3beta-HSD Progesterone to 17alpha-Hydroxy-progesterone via 17alpha-hydroxylase 17alpha-hydroxylase to androstenedione via C17,20-lyase Androstenedione to testosterone via 17β-hydroxysteroid dehydrogenase Ganulosa Cells: Same Progesterone production as thecal cells Androstenedione to estrone via aromatase Testosterone to estradiol via aromatase |
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What is important about GnRH or a synthetic analog administration
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Administration must be pulsatile
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Expansion of the pituitary gland can manifest with what clinically
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Mass effect --> Bitemporal hemianopsia, elevated ICP (headache), seizures, pituitary apoplexia
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What is pituitary apoplexia
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Acute hemmorhage of expanded pituitary gland leading to a rapid depression of conciousness
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Which pituitary adenoma is the most common
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Prolactin producing
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What are the symptoms of a prolactin producing adenoma
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Men - ED, loss of libido, infertility, gynecomastia
Women - amenorrhea, galactorrhea, loss of libido, infertility |
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What drug(s) are used to treat a prolactin producing tumor
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Dopamine receptor antagonists:
Bromocriptine or Cabergoline |
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Describe GH producing tumors
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Increased IGF-1 from liver
Pre-puberty = gigantism Adulthood = acromegaly |
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Describe central diabetes insipidus
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ADH deficiency
Damage to posterior lobe or infundibulum preventing release of ADH Polyuria and polydipsia |
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Describe SIADH
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Opposite of DI, excessive water resorption by kidney
Paraneoplastic - small cell lung cancer |
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Describe a craniopharyngioma (general)
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Most common hypothalamic tumor
Remnant of pouch of rathke Slow-growing, epithelial-squamous, calcified, cystic tumor Two types - Adenomatous and papillary |
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Describe adenomatous craniopharyngioma
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More common in peds
Visual disturbance, DI, anterior pituitary dysfunction Cystic appearance Machinery oil fluid |
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Describe papillary craniopharyngioma
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Adults
Usually extends to third ventricle Papillae and cystic surfaces lined by simple squamous epithelium |
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Describe the process by which the B cell releases insulin
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High glucose enters B cell and is converted to ATP
Increased ATP closes K channel and depolarizes cell beyond Ca voltage gated channel threshold Ca channel opens, increasing intracellular CA levels causing insulin release |
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What are the fast acting "normal" insulins
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Regular insulin
Semilente |
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What are the intermediate-acting "normal" insulins
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Lente
NPH (Neil Patrick Harris) |
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What are the fast acting "modified" insulins
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Lispro
Aspart |
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What are the long acting "modified" insulins
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Glargine
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What are the different types of drugs used to treat Type 2 diabetes
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Sulfonylureas
Meglitinides Starch blockers Biguanides Insulin sensitizers Incretins |
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Describe sulfonylureas in their relation to treating type 2 diabetes
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Blocks K channel of B cells increasing the amount of insulin released
1st gen - tolbutamide, acetohexamide, chlorpropamide 2nd gen - Glipizide, glyburide |
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Describe Meglitinides in their relation to treating type 2 diabetes
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Repaglinide
Closes K channels by binding another SUR subunit Safe for those with renal insufficiency |
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Describe Starch blockers in their relation to treating type 2 diabetes
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Acarbose
Blocks a-glucosidase in intestinal brush border to reduce starch absorption Contraindicated for IBD or intestinal block |
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Describe biguanides in their relation to treating type 2 diabetes
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Metformin
Common first line drug Anti-hyperglycemic reducing hepatic glucose output and increasing peripheral actions of insulin |
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Describe insulin sensitizers in their relation to treating type 2 diabetes
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Rosaglitazone
Enhances sensitivity to insulin |
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Describe incretins in their relation to treating type 2 diabetes
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GIP and GLP-1 are the endogenous incretins
Stimulates insulin secretion and inhibits glucagon release Exenatide - GLP-1 receptor antagonist Sitagliptin - Competitive DPP-4 inhibitor (raises engogenous incretin levels) |
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Describe Type 1 DM
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Autoimmune-mediated destruction of beta cells by T lymphocytes (Type IV hypersensitivity)
See chronic islet inflammation (insulinitis) Polyuria, polydipsia, glycosuria Risk of diabetic ketoacidosis Genetic susceptibility from HLA-DR3/4 |
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Describe the complications of Diabetes
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NEG (AGEs) - accelerated arteriosclerosis --> MI, lower extremity gangrene, Kimmelstiel-Wilson nodules and diffuse glomerulosclerosis, renal failure
Activation of PKC - Causes angiogenesis (retinopathy results), profibrogenic (same issues as NEG) Increased intracellular osmolarity |
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Describe the issues associated with increased intracellular osmolarity
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Cells accumulate glucose as sorbitol causing osmotic damage especially in Schwann cells, pericytes, and the lens of the eye
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Describe pancreatic endocrine neoplasms
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Less aggressive than exocrine neoplasm
Rare Mainly in adults Normally functional Insulinoma Gastrinoma |
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Describe insulinoma
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Most common pancreatic endocrine neoplasm
Hypoglycemia with altered mentation precipitated by fasting or exercise |
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Describe gastrinoma as related to pancreatic endocrine neoplasms
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Hypersecretion of gastrin
Often metastasize before diagnosis and often associated with MEN-1 Can trigger ZE syndrome --> extreme gastric acid secretion --> multiple ulcers non-responsive to normal tx |
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What enzyme converts T4 to T3?
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5'-deiodinase
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What enzyme inactivates T3 to rT3
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5-deiodinase
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Describe the synthesis of thyroid hormone
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Thyroglobulin is synthesized from tyrosine within follicular cells
Iodide cotransported into cell with NA by NIS Transported out into the follicle by Pendrin In follicle is oxidized by TPO to form T3/T4 TSH stimulates mobilization of thyroglobulin-T3/T4 |
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Describe the transport of T3/T4
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80%TBG
20%Albumin |
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What are the mechanisms for action of T3
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Increases number of K+ and Na+ pumps increasing metabolic rate
Increase number of myocardial beta-adrenergic receptors Increase mitochondrial uncoupling protein activity |
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What are the physiological effects of T3
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Increases metabolic rate
Low levels - potentiates insulin, decreases cholesterol metaolism High levels - enhances actions of epi to stimulate glycogenolysis and gluconeogenesis, decreases serum lipids |
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Describe the activation of osteoclasts
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RANKL bind RANK activating c-Src
Can be blocked by osteoprotegrin |
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Describe the activation of osteoblasts
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Cbfa1 activation (BMP and Cbfa1 also differentiate it)
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Where do PTH and Vitamin D act on the kidney? And what do they do there?
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DCT
Vit. D - increases expression of calbindin PTH - stimulates basolateral Na/Ca antiporter |
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Describe the active reabsorption of Ca in the kidney
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Luminal TRPV5/6 channels bring Ca into cell
Calbindin shuttles Ca to basolateral membrane Plasma membrane Ca ATPase and Na/Ca antiporter move Ca out of cell |
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Describe PTH in the body
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Production in response to low serum Ca and high phosphate, inhibited by high Ca and high vit. D
Increases renal Ca reabsorption Increases Vit D production Stimulates osteoclast bone resorption |
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Describe the regulation of vitamin D
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Stimulated by low phosphate and high PTH
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Describe the actions of vitamin D
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Increases serum Ca and phosphate
- Increases intestinal absorption of both - Inhibits PTH production/secretion |
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Describe the actions of calcitonin
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Lowers serum Ca and decreases bone resorption
- Inhibits osteoclasts and increases renal calcium excretion Treats osteoporosis, hypercalcemia, and Paget's disease |
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Describe estradiol's role in calcium homeostasis
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Prevents bone resorption by sensitizing bone mechanoreceptors and possibly increasing osteoblast survival
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Describe testosterone's role in calcium homeostasis
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Activity mainly from conversion to estradiol
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Describe growth hormone's role in calcium homeostasis
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Increases bone remodeling --> increased bone mass
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Describe thyroid hormone role in calcium homeostasis
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In excess, increases bone resorption and increases serum Ca levels
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Describe PTH-related peptide (PTHrP) role in calcium homeostasis
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Tumor source of a peptide similar to PTH leading to hypercalcemia of malignancy
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What are the symptoms of hypercalcemia
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Stones, bones, and groans
-Kidney stones - Pain in bones and joint - Fatigue, depression, and weakness Also polydipsia and polyuria |
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Describe primary hyperparathyroidism
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Excess PTH (from adenoma, etc.)
Increased vitamin D |
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Describe hypercalcemia of malignancy
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Three mechanisms:
- PTHrP: like excess PTH, increased urinary cAMP, no increase in vitamin D, treat with Bisphosphonates and Prednisone - Local factors: paracrine increase in bone resorption, no increased cAMP or vit D - Vit D related: (rare), Lymphoma expresses 1-alpha-hydroxylase increasing active vit D, kidneys can compensate unless diseased |
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Describe hypocalcemia
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Arrhythmias, numbness, bronchospasm, seizures
Lack of PTH or lack of vit. D; treat with calcium gluconate and calcitriol |
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What cells make calcitonin
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C-cells (parafollicular cells)
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Describe the congenital abnormalities of the thyroid gland
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Lingual thyroid - most common ectopic thyroid, midline tongue base
Thyroglossal duct cyst - Persistent tract, asymp. neck mass with gelatinous contents (remove part of hyoid bone too) Pyramidal lobe - normal variant |
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What are the three types of thyroiditis that we are concerned with
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Subacute granulomatous
Riedel Hashimoto's |
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Describe subacute granulomatous thyroiditis
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Tender, enlarged thyroid with fever
Post viral infection Self-limited Initially high T3/T4 returns to normal |
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Describe Riedel thyroiditis
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very rare
Painless "WOODY" texture thyroid Fibrosis Surgical excision |
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Describe Hashimoto's thyroiditis
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aka autoimmune chronic lymphocytic thyroiditis
Most common cause of hypothyroidism where iodine is sufficient Painless symmetrical pale/tan, nodular enlargement Increased risk of B-cell non-Hodgkin's lymphomas Thyroid follicles replaced by lymphocytes and lymphoid follicles with germinal centers Hurthle cell metaplasia (eosinophilic and granular follicular epithelium) |
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Describe Graves disease
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Hyperthyroidism from diffuse toxic goiter
IgG autoantibodies act as TSH receptor antagonists (Type II hypersensitivity) = TH secretion - Increased metabolism - Heat intolerance - Weight loss - Possible thyroid storm Red meaty appearance of thyroid Tall columnar follicular cells, scalloped colloid |
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What are the causes of hypothyroidism
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Insufficienct thyroid parenchyma (ie hashimoto's)
Interference with TH synthesis (iodide deficiency) Suprathyroidal problems (pituitary or hypothalamus issues) |
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Describe adult hypothyroidism
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myxedema
Treat with thyroid hormone replacement Decreased BMR Accumulation of MPS --> non-pitting edema, delayed reflexes, decreased Q from enlarged heart |
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Sporadic goiter is often seen in
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pregnancy and adolescent females
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What is the most common thyroid carcinoma
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Papillary carcinoma
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Describe papillary carcinomas of the thyroid
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Most common
Good prognosis Lymphatic spread Psammoma bodies "orphan annie" nuclei (empty, optically clear) |
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Describe follicular carcinomas of the thyroid
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Second most common
Worse prognosis Almost never in kids Hematogenous spread with bone mets |
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Describe medullary carcinomas of the thyroid
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Uncommon, sporadic or familial (MEN IIA or IIB)
Arises from C cells Produces calcitonin Amyloid deposits |
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Describe congenital parathyroid pathologies
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Ectopic or absent (DiGeorge Syndrome) - Chromosome 22 defect
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Describe hyperparathyroidism
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PTH secreting parathyroid adenoma or nodular hyperplasia
"Stones, bones, and groans" Secondary - most commonly due to chronic renal failure leading to phosphate retention |
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Describe parathyroid nodular hyperplasia
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Solid chief cells with nodular architecture and little fat
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If a female patient has low TSH and high T3/T4, they should be checked for
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pregnancy
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What is the therapy for thyrotoxicosis (hyperthyroidism)
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Methimazole, but possibly teratogenic, so use PTU instead in pregnant women
Radioactive iodine |
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What causes increased TSH and PRL in hypothyroidism
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Elevated TRH
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Elevated TRH is hypothyroidism causes what
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Elevated TSH and PRL
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What is a good marker for Hashimoto's disease
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Increased antithyroid peroxidase anitbodies
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What is a possible treatment modality for hypothyroidism
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levothyroxine-L-T-4 (Levoxyl/Synthroid)
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A normal reading for glycosylated hemoglobin and fasting plasma glucose is
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Glycosylated hemoglobin - <5.6%
Fasting glucose - <100 |
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A Pre-Diabetes reading for glycosylated hemoglobin and fasting plasma glucose is
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Glycosylated hemoglobin - 5.7-6.4%
Fasting glucose - 101-125 |
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A Diabetes reading for glycosylated hemoglobin and fasting plasma glucose is
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Glycosylated hemoglobin - >6.5%
Fasting glucose - >126 |
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DKA is associated with what form of diabetes
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Type 1
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Nonketotic hyperosmolality syndrome is associated with what form of diabetes
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Type 2
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What are the musculoskeletal disorders associated with DM
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Hand: dupuytren’s contracture, trigger finger, carpal tunnel syndrome
Shoulder: adhesive capsulitis (frozen shoulder), tendinitis. Neuropathic arthropathy due to loss of sensation Spontaneous muscle infarction |
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The glomerulosa of the cortex of the adrenal gland produces what and has what receptor
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Aldosterone
AII receptor |
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The fasciculata of the cortex of the adrenal gland produces what and has what receptor
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Cortisol
ACTH receptor |
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The reticularis of the cortex of the adrenal gland produces what
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DHEA
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The medulla of the adrenal glands produces what
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catecholamines
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How does ACTH stimulate the production of cortisol
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Stimulates cholesterol esterase and increases production of CYP 11A and StAR which increases transport of cholesterol into mitochondria
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Describe the most common enzyme deficiency of the adrenal cortex involving cortisol production
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21-hydroxylase deficiency
Results in excess androgen production from lack of negative feedback on ACT AKA Congenital Adrenal Hyperplasia |
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How is cortisol transported in the blood
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95% bound to transcortin and albumin
5% free |
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When is cortisol highest
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AM
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What are the functions of cortisol
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Catabolic in periphery, anabolic in liver
Causes fat redist to trunk Block inflammation and immune response Increases gluconeogenesis and decreases glucose uptake Increases FFA mobilization Increased appetite Maintains vascular tone |
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Overexposure of cortisol in children can cause
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inhibition of bone growth
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A lack of 11beta-HSD2 results in what
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Inability to inactivate cortisol leading to an apparent mineralocorticoid excess
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Describe the release of aldosterone
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Stimulated by K+ and A-II (and ACTH)
Inhibited by ANP and adrenomedullin |
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Aldosteronism may be treated with what
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Spironolactone or *eplerenone*
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Pheochromocytoma surgery should be preopped with what
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phenoxybenzamine
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What are the adipokines
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Adiponectin
Leptin Resistin |
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What does adiponectin do
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Inhibits TNFalpha production
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What does leptin do
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Activates macrophages and increases TNFalpha and IL-6
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What does resistin do
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Increases TNFalpha and IL-6 production
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What does TNFalpha do
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Inhibits LPL causing hypertriglyceridemia
Increases lipolysis *Causes insulin resistance via JNK activation* Contributes to endothelial dysfunction |
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What are the inflammatory mediators associated with obesity
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TNFalpha
sRB-4 CRP |
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Metabolic syndrome is defined by having three or more of what symptoms/characteristics
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Abdominal obesity
Fasting blood TG>150mg/dL Low HDL borderline HTN Fasting glucose>100 |
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What hormones are derived from neural tissue
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Oxytocin and vasopressin
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What cells (that we're concerned with for now from the adenohypophysis) stain pink
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GH producing
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Oral glucose --> ? --> Insulin release
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? = GIP production
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If a diabetic is allergic to TMS, what should be used
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Metformin
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What may be observed on supplemental T3 therapy
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Increased T3
Decreased TSH and T4 |
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What is the main principal behind the mechanism of action of PTU
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Inhibits deiodination of T4 and thyroglobulin
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Erosion of phalanges and metaphyseal reabsorption of radius and ulna might be indicative of what
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PTH excess
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Pioglitazone does what
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Decreases hepatic glucose output
Increases peripheral glucose utilization |
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Solid balls of neoplastic follicular cells, microscopic blood vessels and fibrous stroma in centers are indicative of what
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Papillary carcinoma
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Verticle purple striae, intracapsular fat, increased ACTH, increased cortisol are suggestive of
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Cushing's disease
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Cushing's disease treatment that can show a large reduction in cortisol levels
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Dexamethasone
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Will ectopic tumors producing cortisol be suppressed by dexamethasone
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No
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Increased calcium, decreased phosphate, increased urinary cAMP, constipation, and weakness suggest
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Primary hyperparathyroidism
(increased cAMP says not vitamin D) |
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Describe the possible causes of cushing's syndrome based on ACTH levels and response to dexamethasone
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Adrenal Tumor: ACTH low, Dexa-non suppression
Cushing's Disease: ACTH normal, Dexa suppression Ectopic ACTH: ACTH high, Dexa-non suppression |
