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215 Cards in this Set
- Front
- Back
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3 classes of endocrine secretions
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steroids and cholesterol
small peptides, proteins, glycoproteins amino acid analogs and derivatives |
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True or False: the class of secretion is reflected in the histological structure of the organ secreting it?
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True
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Direction of portal system in pituitary
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from posterior lobe to anterior lobe
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What bony structure houses the pituitary?
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sella turcica of the sphenoid bone
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pituitary gland, aka:
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hypophysis
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A stalk-like ____ connects the pituitary to the hypothalamus
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A stalk like INFUNDIBULUM connects the pituitary to the hypothalamus
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anterior lobe of pituitary gland, aka:
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adenohypophysis
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posterior lobe of pituitary gand, aka:
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neurophyophysis
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embryological origin of anterior lobe of pituitary
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Rathke's pouch,
an invagination of the ECTODERM of the oropharynx |
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3 parts of anterior lobe of pituitary
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Pars distalis
Pars intermedia Pars tuberalis |
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Type of tissue comprising anterior lobe
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glandular epithelium
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colloid filled follicles surrounded by parenchymal cells of the pars intermedia of pituitary
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Rathke's cysts
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Part of anterior pituitary that wraps the infundibulum in a sheath
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Pars tuberalis
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Part of pituitary that separates the anterior and posterior lobe
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Pars intermedia
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Highly vascular part of anterior pituitary
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Pars tuberalis
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5 types of secretory cells present in pars distalis of anterior pituitary
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Somatotropes
Lactotropes Corticotropes Gonadotropes Thyrotropes |
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Gonadotropes produce...
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LH
FSH |
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Lactotropes produce....
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prolactin (PRL)
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somatotropes produce...
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GH
somatotropin |
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Corticotropes produce...
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ACTH
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Thyrotropes produce...
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TSH
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The veins of which system run through the pars tuberalis?
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hypothalamohypophyseal system
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Two things found in pars intermedia
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colloid filled follicles
cystic cavities |
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Which pituitary lobe is an endocrine gland?
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ANTERIOR
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Two regions of posterior pituitary
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pars nervosa
short stalk of infundibulum |
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Embryological origin of posterior pituitary
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neuroectoderm of fourth ventricle
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hypothalamohypophyseal tracts connect ____ to the _____ and ______ of the hypothalamus
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Hypothalamohypophyseal tracts connect the POSTERIOR PITUITARY to the SUPRAOPTIC and PARAVENTRICULAR NUCLEI of the hypothalamus
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The nerve endings of the hypothalamohypophyseal tracts act as a storage site for what?
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the neurosecretions of the hypothalamus en route to the posterior pituitary (neurophypophysis).
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What type of axons do the hypothalamohypophyseal tracts have?
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unmyelinated neursecretory axons
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Which pituitary lobe has a direct arterial supply?
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POSTERIOR
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Portal circulation in pituitary
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See CP. p. 50
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The pineal gland is sensitive to what?
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LIGHT
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To what neural structure is the pineal gland attached?
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posterior wall of the third ventricle
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Embryological origin of pineal gland
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neuroectoderm of diencephalon
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Major hormone of pineal gland
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melatonin
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Melatonin is responsible for what 3 things
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circadian rhythms
reproductive activity regulating emotional states associated with SAD |
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Parenchymal cells of pineal gland are called...
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pinealocytes
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small calcified concretions in human pineal gland, located in midbrain
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corpora arenacea
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3 hormones secreted by thyroid
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T3
T4 calcitonin |
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Calcitonin function
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decrease blood calcium levels by regulating deposit and resorption of calcium in bone
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T3 and T4 functions (4)
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basal metabolism and thermoregulation
body and tissue growth development of nervous system increases carb absorption from intestine |
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pyramidal lobe of thyroid
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fingerlike projection that may extend upward toward the thyroid carticlage
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arteries supplying thyroid
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superior and inferior thyroid aa.
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each thyroid lobe is made up of thousands of _____
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follicles
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these strctures are made up of gellike colloid droplets lined by simple cuboidal follicular (principle) cells
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thyroid gland follicles
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apices of thyroid follicular cells are in contact with ____
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colloid
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function of microvilli on apices of thyroid follicular cells
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support synthesis and resorption of colloid
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which thyroid cells produce T3 and T4?
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principal (follicular) cells
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What hormone increases size and activity of thyroid follicular cells?
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TSH
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Levels of these 4 things increase when thyroid follicular cells are stimulated by TSH
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iodide transporters
extracellular thyroglobulin synthesis endocytosis lysosomal activity |
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What two hormones down regulate the sunthesis of thyroid hormones
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T3 and T4
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Which type of thyroid cell secretes CALCITONIN
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parafollicular thyroid cell
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What type of capillaries supply the follicles of the thyroid?
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fenestrated
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Where are the parathyroid glands located?
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buried in the CT of the posterior thyroid
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function of parathyroid glands
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regulate calcium and phosphate levels in the body
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absence of parathyroid hormone (PTH) causes:
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fall in blood calcium levels
--> uncontrolled spasmodic contraction of essential muscles (i.e.: laryngeal and respiratory) --> DEATH |
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embryological source of parathyroid glands
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3rd and 4th branchial pouch
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are the parathyroid glands encapsulated?
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YES
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main arterial supply to parathyroid glands
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inferior thyroid aa
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two cell types that form the parenchyma of the parathyroid
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chief cells
oxyphil cells |
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Which cells of the parathyroid parenchyma secrete PTH?
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chief cells
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What structures carry blood vessels and nerves into parenchyma of the adrenals?
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trabeculae - extendtions of the capsular CT
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In the adrenals, the parenchyma is divided into the ____ and _____
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cortex
medulla |
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Which hormones do the cortices of the adrenals secrete?
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steroid hormones
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Which hormones do the medullae of the adrenals secrete?
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catecholamines
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embryological source of the adrenal cortex
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mesodermal mesenchyme
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embryological source of the adrenal medulla
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neural crest cells
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secretions from the ____ _____ gland help regulate the cell function of the adrenal cortex
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anterior pituitary
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adrenal cortex regulates ____ & _____
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adrenal cortex regulates METABOLISM and ELECTROLYTE BALANCE
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adrenal blood supply
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superior and middle suprarenal aa
branches of tha aorta inferior suprarenal aa (branch of renal a.) |
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Adrenal medullary circulation is derived from _____ and _____
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arterial blood
cortical sinusoidal capillaries |
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Function of adrenomedullary veins
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reduce volume of adrenal glands
enhance release of hormones from adrenal medulla |
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function of lymphatic vessels in adrenal glands
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distribute high MW secretory products of chromaffin cells, e.g.: chromagranin A, to systemic circulation
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3 types of endocrine pancreas secretory cells and their products
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alpha cells - glucagon
beta cells - insulin (& gastrin) delta cells - somatostatin |
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Percentage of Islets of Langerhans that are...
alpha cells beta cells delta cells F cells |
alpha cells - 20-25%%
beta cells - 65-75%% delta cells - 3-10% F cells - < 2% |
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blood supply for pancreas
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gastroduodenal aa
splenic a superior mesenteric aa |
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vascular structure characteristic of endocrine glands
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capillary portal system
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which type of secretory pancreatic cells are on the periphery of the Islets and are perfused by the portal system first?
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alpha and delta cells
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the pancreatic capillary system allows hormones from the ____ to influence the acinar glands of the _____
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The pancreatic capillary system allows hormones from the ENDOCRINE PANCREAS to influence the acinar glands of the EXOCRINE PANCREAS
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Which 3 pancreatic hormones INHIBIT exocrine secretion?
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glucagon
pancreatic polypeptide somatostatin |
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Which 3 pancreatic hormones STIMULATE exocrine secretion?
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insuline
vasoactive intestinal peptide CCK |
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Diffuse endocrine cells =
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individual or small clusters of endocrine cells scattered throughout the epithelium of the digestive and respiratory systems
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5 types of diffuse endocrine cells
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chromaffin cells
argentaffin cells function APUD cells DNES GEP endocrine cells |
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actions of insulin are anabolic or catabolic?
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ANABOLIC
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actions of glucagon are anabolic or catabolic
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CATABOLIC
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3 principle determinants of BGL
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dietary intake
rate of entry into muscle and adipose cells whether liver is taking up or excreting glucose into the plasma |
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point average for normal BGL
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70 mg/dL
(3.9 mmol/L) |
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When plasma glucose > ____ mg/dL, glucose is excreted in the urine
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> 180 mg/dL
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Where is proinsulin cleaved into insulin and C-peptide?
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within secretory vesicles of the beta cells
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Insuline and C-peptide are secreted in ____ amounts
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equimolar
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What organ is exposed to the highest concentrations of insulin? Why?
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LIVER
insulin travels from pancreas to liver through hepatic portal veins. about half of that insulin is degraded in the liver. |
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Half life of insulin in peripheral circulation
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5 minutes
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Why use C-peptide assay instead of endogenous insulin assay in patients undergoing exogenous insulin tx?
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insulin assay doesn't work
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4 factors controlling insulin secretion
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nutrients
hormones nervous system drugs |
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Factors that INHIBIT insulin secretion
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sympathetic nerve stimulation (NE, Epi)
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3 major factors that stimulate insulin secretion
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Vagal nerve stimulation (Ach)
sugars, amino acids gut hormones |
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sugar that inhibits insulin secretion
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2-deoxy glucose
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hormones that stimulate insulin secretion
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pancreatic glucagon
gut hormones: GLP-1, GIP, CCK, gastrin, secretin |
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hormones that inhibit insulin secretion
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pancreatic somatostatin
epi |
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drugs that stimulate insulin secretion
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sulfonylureas
meglitinides incretin (gut hormone) analogs |
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Somatostatin analogs are used clinically to suppress...
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secretion of insulin, glucagon and other hormones
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time after eating when second insulin peak occurs
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~ 1 hr
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In some patients with DM, the pancreas can secrete insulin, but...
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the first phase of insulin secretion is lacking or subnormal
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Insulin favors anabolism and nutrient storage by promoting (4 things):
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synthesis & deposition of glycogen in liver and muscle
synthesis of lipids in liver, adipose uptake/storage of lipids in adipose tissue uptake of amino acids & protein synth in muscle |
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Insulin ___ BGL;
Glucagon ___ BGL |
Insulin LOWERS BGL
Glucagon RAISES BGL |
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Glucagon secretion is stimulated by (5 things):
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hypoglycemia
amino acids gut hormones parasympathetic nerves (Ach, Vagal) sympathetic nerves (NE) |
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Glucagon secretion is inhibited by (3 things)
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hyperglycemia
fatty acids somatostatin |
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Metabolic actions of glucagon (4 things)
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promotes hepatic ketone body synthesis
increases glycogen breakdown increases hepatic GNG increases lipolysis |
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Mechanism of action of glucgaon on target cells
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Glucagon + G protein-coupled receptors -->
increased cAMP via AC stimulation OR increased cytsolic Ca2+ via IP3 formation |
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Insulin enhances...
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glucose uptake (indirectly)
glycogen synthesis glycolysis |
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Glucagon enhances
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glycogenolysis
GNG |
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What is more important than the absolute level or insulin or glucagon?
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the I/G ratio
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low I/G ratio promotes:
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hepatic glucose output
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which type of biomacromolecule stimulates glucagon secretion
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protein
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signs and symptoms of hypoglycemia
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tachycardia
diaphoresis tremor hunger irritability HA LOC behavioral abnormalities seizures coma |
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changes in glucose, glucagon, GH, cortisol and epi after insulin administration
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see CP p. 79
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insulin -induced hypoglycemia is an omnipresent risk of...?
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exogenous insulin administration
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4 " counter-regulatory" hormones released in response to insulin-induced hypoglycemia
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epinephrine
glucagon cortisol growth hormone |
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6 functions of epinephrine in response to insulin-induced hypoglycemia
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suppresses insulin release
increases glucagon release increases lipolysis increases glycogen breakdown enhances hepatic GNG decreases glucose uptake by muscle, fat |
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3 functions of cortisol in response to insulin-induced hypoglycemia
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decreases glucose uptake by muscle, fat
serves permissive role for lipolysis & GNG in excess, can stimulate protein breakdown |
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3 functions of GH in response to insulin-induced hypoglycemia
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decreases glucose uptake by muscle, fat
increases lipolysis, hepatic GNG promotes KB synthesis in liver |
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Even at very low concentrations, insulin is a potent inhibitor of what metabolic pathway?
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lipolysis
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4 hormones responsible for control of lipolysis
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hormone sensitive lipase
insulin epi lipoprotein lipase (LPL) |
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Function of hormone sensitive lipase wrt lypolysis
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--> lypolysis and release of glycerol and FFA from adipose tissue
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Function of insulin wrt lypolysis
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suppresses release of FFA from adipose tissue by inhibiting hormone sensitive lipase
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function of epi wrt lipolysis
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enhances FFA mobilization by activating hormone sensitive lipase
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function of LPL wrt lipolysis
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enzyme that allows plasma lipoproteins to deposit their TGs into adipose tissue for storage
enhanced by insulin |
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why is glycerol released by lipolysis normally not reused by adipocyte for reesterification?
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futile cycle!
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Glycerol-3-P can be used for ____ & ____
What is necessary for its generation? |
Glycerol-3-P can be used for FFA esterification and TG storage
insulin-mediated glucose uptake by the adipocyte is necessary for its generation |
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4 consequences of lipolysis and delivery of FFA to the liver
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enhanced FFA oxidation
production of KBs FFA stimulate GNG enhanced synthesis of VLDL |
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Which KB is the only one measured by usual clinical tests? What is the consequence?
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Acetoacetate
beta-hydroxybutyrate usually exceeds acetoacetate greatly; ergo, tests significantly underestimate KB concentration |
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the 4 " polys" of diabetes
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polyuria
polydipsia polyphagia weight loss |
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insulin deficiency leads to ___ & ____
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dehydration
acidosis |
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signs and symptoms of DKA
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polyuria & polydipsia, dehydration
N/V AP & distention wt loss fruity (acetone) breath Kussmaul resps cool, dry skin Low BP drowsiness coma |
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General definition, Type 1 DM
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body completely loses ability to produce insulin
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General definition, Type 2 DM
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body's cells become resistant to effects of insulin
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6 general characteristics of type 1 DM
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absolute insulin deficiency
dependent of exogenous insulin for life prone to DKA recent wt loss abrupt onset of symptoms usu. before age 30 |
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" vicious cycle" of Type 2 DM
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insulin resistance --> increased insulin secretion --> down regulation of insulin receptors --> more insulin resistance
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What percentage of insulin receptors are considered "spare"?
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90% (do not need to be bound for insulin to affect cells)
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If 90% of insulin receptors are spare, why does down regulation shift insulin-dose response curve to the right?
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b/c decreased numbers of receptors lower the likelihood of overall insulin molecule binding
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With obesity &/or type 2 DM, insulin resistance usu. develops from ___ & _____
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post-receptor defects in insulin action
& decreased insulin receptor number |
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Insulin dose-response curve in type 2 DM, relative to normal
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shift to right
+ lower maximal response (even at high insulin concentrations) |
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OGTT
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oral glucose tolerance test:
drink 75g glucose & measure BGL every 30 min from fasting through 2 hrs not rec'd for routine clinical use |
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Compared to lean persons, obese persons secrete ____ insulin and have _____ insulin levels.
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Compared to lean persons, obese persons secrete MORE insulin and have HIGHER insulin levels.
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2 factors implicated in reversal of insulin resistance in obese persons
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dietary restriction
weight reduction |
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Post-receptor defects in type 2 DM can produce:
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decreases in glucose transport activity
defects in glucose metabolism |
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Compare and contrast Type I and Type II DM
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see CP 104
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A ds is considered "genetic" if
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concordance is 100% in identical twins
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Genetic concordance of
Type I DM Type II DM |
Type I DM: <50% concordance
Type II DM: 90-100% concordance |
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6 major complications of DM
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microvascular (retinopathy, renal ds)
macrovascular neuropathy increased susceptibility to infections foot ulcers cataracts |
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3 tx factors for Type I DM
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insulins
diet exercise |
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Typical insulin combination for tx
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long acting (e.g.: Glargine) + rapid-acting (eg: Lispro) before each meal
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What makes Lispro act more rapidly than other insulins?
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structurally altered to hinder ability to form dimers. monomers are absorbed more rapidly than regular insulin.
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2 goals of insulin tx
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mimic naturally occuring peaks of insulin that follow meals
maintain basal level of insulinemia btw meals |
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structural addition btw HbA and HbA1c
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glucose attached to NH2 terminus for beta chain by ketoamid linkage
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HbA1c is formed ____ly and ____ly during the ____-day lifespan of the RBC
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HbA1c is formed SLOWLY and IRREVERSIBLY during the 120 day lifespan of the RBC
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extent of AbA1c accumulation depends on...
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average concentration of glucose in plasma during the 2-3 months before measurement
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Preprandial glucose
Nondiabetic/diabetic goal Peak postprandial glucose HbA1c |
Preprandial: <100 / 90-130
Postprandial: <140 / <180 HbA1c: <6 / <7 |
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AGEs
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advanced glycation endproducts
(of proteins) alter protein function |
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Intracellular sorbitol accumulation in DM
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RBCs, NS cells and kidneys take in high concentrations of glucose during hyperglycemia b/c they are not insulin-dependent
excess glucose is converted to sorbital --> neuropathy, cataract formation, etc |
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3 biochemical pathways to DM complications
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glycation of proteins
intracellular sorbitol oxidative stress & formation of free radicals |
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7 hormones secreted by the hypothalamus
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Growth hormone releasing hormone (GHRH)
Thyrotropin releasing hormone (TRH) Gonadotropin releasing hormone (GnRH) Somatostatin Corticotropin releasing hormone (CRH) Prolactin releasing factor (PRF) Prolactin inhibitory hormone (dopamine) |
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Somatostatin inhibits the production/secretion of which two hormones in the pituitary?
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GH
TSH |
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Dopamine inhibits the production/secretion of which hormone in the pituitary?
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Prolactin
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Function of PROLACTIN
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breast development and milk production
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Function of FSH, LH
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gonadal & germ cell development & hormone production --> sex steroids
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ACTH function
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adrenal cortex --> cortisol
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TSH function
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--> thyroid hormones
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INDIRECT effects of GH
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liver --> IGF-I
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DIRECT effects of GH
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--> liver and other tissues
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Long-acting somatostatin analogs are used to tx (3 conditions):
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pituitary tumors secreting GH
pancreatic tumors secreting excess insulin gut neuroendocrine tumors secreting serotonin, VIP |
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Panhypopituitarism
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complete loss of pituitary function
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5 causes of pituitary insufficiency
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pituitary tumors
hypothalamic damage pituitary infaction/necrosis head trauma/neurosurgery non-pituitary tumor |
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Two tests for hypothalamus & pituitary
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baseline hormone levels
insulin-induced hypoglycemia |
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Explain baseline hormone level testing for hypothalamus and pituitary
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mea. basline levels of pituitary hormones and their target hormones, e.g.: TSH + thyroid hormones; ACTH + cortisol
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Explain insulin-induced hypoglycemia for hypothalamus/pituitary testing
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normally, insulin adminitration --> hypoglycemia --> ACTH, GH, prolactin production
Failure of these hormone levels to rise suggests pituitary insufficiency |
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3 nocturnal hormones
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GH
PRL ACTH |
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factors that stimulate GH secretion
factors that inhibit GH secretion |
GH stimulation: hypoglycemia, sleep, exercise, stress
GH inhibition: glucose ingestion, somatostatin |
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Increased pituitary GH secretion can be caused by what 2 hormone factors?
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Increase in GHRH
Decrease in somatostatin |
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The greater the negative feedback effects of IGF-I, the ____ the pituitary is willing to secrete GH to any given hypothalamic stimulatory signal.
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The greater the negative feedback effects of IGF-I, the LESS the pituitary is willing to secrete GH to any given hypothalamic stimulatory signal.
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Isolation of the anterior pituitary from the hypothalamus causes:
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GH deficiency
|
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Direct effects of GH
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reduced glucose uptake
increased heatpic GNG increased lipolysis & ketogenesis increased aa uptake & prtin synthesis increased cell proliferation |
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Indirect anabolic effects of GH
via: |
via IGF-I
increased skeletal growth increased aa uptake & prtn synthesis increased cell proliferation |
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Laron syndrome
|
short stature results from a deficiency of the hormone IGF-I, which mediates most of the growth promoting effects of GH
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What organ produces IGF-I?
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Liver
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When does IGF-I peak during the human lifespan?
|
puberty
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6 groups of hormones influencing growth
|
GH
insulin thyroid hormones androgens estrogens (promote epiphyseal closure) glucocortidoids (inhibit somatic growth) |
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4 points of assessment in evaluating a child for possible causes of growth retardation
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assess nutritional status
assess GH responsiveness to stimuli measure GH measure thyroid hormones |
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How must GH be administered?
|
subcutaneous injection
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If it occurs prior to the closure of the epiphyses, excess GH can cause:
After closure of epiphyses, it can cause: |
before: giantism
after: acromegaly |
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3 factors in diagnosing GH excess
|
elevated basal plasma GH concentration
GH is not suppressed following glucose administration elevated IGF-I plasma concentration |
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hypothalamic control of PRL secretion is predominantly:
stimulatory/inhibitory? |
inhibitory
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Disruption of the hypothalamic-pituitary connection ______ PRL secretion
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increases
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Prolactin's negative feedback inhibition
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PRL facilitates secretion of dopamine from the hypothalamus.
Dopamine inhibits PRL secretion from the pituitary. |
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Factors that stimulate PRL secretion
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estrogen (e.g: pregnancy)
nursing sleep stress TRH dopaminergic antagonists |
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Factors that inhibit PRL secretion
|
dopamine
dopamine agonists (e.g.: L-Dopa) PRL |
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most common tumor of pituitary
|
PRL-secreting adenoma
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Effects of excess PRL
|
galactorrhea
interference w/ GnRH secretion inhibition of gonadal steroid production --> amenorrhea, ED/infertility |
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Effects of TSH
|
increased synthesis and secretion of thyroid hormones
thyroid gland enlargement |
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thyroid hormones are stored...
|
in the colloid, attached to thyroglobulin
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3 steps in thyroid hormone synthesis
|
iodide trapping
iodide organification coupling of residues |
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During illness/fasting, what happens with T4 and T3?
|
Production of T3 from T4 is slowed
T4 --> inactive rT3 --> less thyroid activity --> decreased BMR |
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low T3 state is associated with what drug type?
|
glucocorticoids
|
|
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Proteins that bind steroid and thyroid hormones in the blood
|
Thyroid Binding Globulin (TBG)
Cortisol Binding Globulin (CBG) Sex Hormone Binding Globulin (SHBG) albumin & prealbumin |
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Only the ____ hormone is active
|
FREE
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10x more T___ is bound in the blood than T____
|
10x more T4 is bound than T3.
Therefore, proportion of free T3 is 10x greater than free T4 |
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|
Effects of thyroid hormones
|
CP p. 161
|
|
|
Congenital hypothyroidism results in
|
mental retardation (cretinism) if left untreated
|
|
|
Relationship between thyroid hormones and catecholamines
|
Thyroid hormones enhance effects of catecholamines and the SNS by increasing the number of beta adrenergic receptors in target tissues
--> e.g.: increased HR |
|
|
General mental effects of thyroid hormones in adults
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increase mental alertness and responsiveness to external stimuli
velocity of condition of APs in peripheral nerves increases with increased thyroid hormone levels |
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Effects of HYPOthyroidism on protein metabolism
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impaired protein synthesis
reduced GH secretion decreased linear growth |
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Effects of HYPERthyroidism on protein metabolism
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net catabolism of protein
muscle concentrations of creatine phosphate reduced |
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Both hypo- and hyperthyroidism ____ normal (positive) nitrogen balance
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Both hypo- and hyperthyroidism REDUCE normal (positive) nitrogen balance
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Calcium balance positive/negative with hyperthyroidism?
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NEGATIVE
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Two types of HYPOthyroidism
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primary (thyroid failure) - TSH high
secondary (pituitary failure) - TSH low |
