Physiology Flashcards
Where in the cell is preproinsulin made?
Rough ER
Where is proinsulin stored?
Secretory granules
What conditions increase insulin and C-peptide?
Insulinoma an sulfonylurea use
Insulin and C-peptide are secreted in what amounts in relation to each other?
Equally
Insulin receptors have what type of enzymatic activity?
Tyrosine kinase activity
What does binding of insulin induce?
Glucose uptake and gene transcription
What are the effects of insulin on skeletal muscle and adipose tissue?
Increased glucose transport into those tissues
What are the effects of insulin on glycogen?
Increased glycogen synthesis and storage
What are the effects of insulin on triglycerides?
Increased triglyceride synthesis
What are the effects of insulin on sodium?
Increased sodium retention in kidneys
What are the effects of insulin on protein?
Increased protein synthesis in muscle
What are the effects of insulin on potassium?
Increased cellular uptake of potassium
What are the effects of insulin on glucagon?
Decreased glucagon release
What are the effects of insulin on lipolysis?
Decreased lipolysis in adipose tissue
What are the effects of insulin on the fetus?
None, cannot cross the placenta
Which GLUT transporter is insulin dependent?
GLUT4
Where are GLUT4 transporters found in the body?
Skeletal and adipose tissue
What activity can increase expression of GLUT4 transporters?
Exercise
What GLUT transporters are insulin independent?
GLUT1, GLUT 2, GLUT3, GLUT5
Where are GLUT1 transporters found in the body?
RBCs, brain, cornea, placenta
Which GLUT transporter is bidirectional?
GLUT2
Where are GLUT2 transporters found in the body?
B islet cells, liver, kidney, and small intestine
Where are GLUT3 transporters found in the body?
Brain and placenta
Where are GLUT5 transporters found in the body?
Spermatocytes and GI tract
Which GLUT transporter uptakes fructose
GLUT5
What molecule does the brain utilize for energy during starvation?
Ketones
What molecule does the brain normally use for energy?
Glucose
Why are RBCs only able to utilize glucose for energy?
They lack mitochondria for aerobic metabolism
What tissues are insulin-independent for glucose uptake?
Brain, RBCs, Intestine, Cornea, Kidney, Liver (BRICK L)
What is the major regulator of insulin release?
Glucose
What cell signaling molecule does insulin use in insulin-dependent glucose uptake?
Tyrosine kinase
What regulatory molecules are released after oral ingestion of glucose that stimulate insulin release?
Glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic peptide (GIP)
What is the effect of GLP-1 and GIP on beta cells?
Increased beta cell sensitivity to glucose
Stimulation of which adrenergic receptors decreases insulin release?
Alpha-2
Stimulation of which adrenergic receptors increase insulin release
Beta-2
What is the effect of glucose entering a pancreatic beta cell?
Increased ATP from glucose metabolism
What is the affect of increased ATP in a pancreatic beta cell?
Increased ATP closes potassium channel
What is the affect of closing the potassium channel in a pancreatic beta cell?
Depolarization of the membrane
What is the affect of depolarization of the membrane in a pancreatic beta cell?
Opens voltage-gated calcium channels
What is the affect of increased calcium in a pancreatic beta cell?
Exocytosis of insulin granules
What cells of the pancreas make glucagon?
Alpha cells
What causes secretion of glucagon?
Hypoglycemia
What inhibits glucagon release?
Insulin, hyperglycemia and somatostatin
Gluconeogenesis and glycogenolysis are mediated by what hormone?
Glucagon
What effect does cortisol have on glucagon?
Permissive effect allowing glycogenolysis
Increased ketone production is caused by what hormone?
Glucagon
What hypothalamic hormone is decreased with chronic steroid use?
CRH
What pituitary hormones are increased by CRH?
ACTH, MSH, and B-endorphin
What hypothalamic hormone decreases release of prolactin?
Dopamine
What is the effect of some antipsychotics on dopamine release?
Decreased dopamine release causing hyperprolactinemia which leads to galactorrhea and amenorrhea, osteoporosis and hypogonadism
Regulates release of GH from anterior pituitary
GHRH
Regulates release of FSH and LH from anterior pituitary
Pulsatile GnRH
What is the effect of tonic release of GnRH?
Suppresses HPG axis, decreased LH and FSH release
What is the effect of pulsatile release of GnRH?
Leads to puberty and fertility, increased LH and FSH release
What suppresses release of GnRH?
Hyperprolactinemia
What is the function of prolactin?
Decrease GnRH release, promote milk production, decrease ovulation in women and spermatogenesis in men
What are the affects of a pituitary prolactinoma?
Amenorrhea, galactorrhea, osteoporosis, and hypogonadism
What is the affect of somatostatin on GH and TSH
Decreases release of GH and TSH
What is the analog of somatostatin used for?
Treat acromegaly
What is the somatostatin analog?
Ocreotide
Prolactin release is stimulated by what hypothalamic hormone?
TRH
What is the function of TRH?
Increase release of TSH and prolactin
What pathologic conditions increase TRH?
Primary and secondary hypothyroidism
What is the effect of increased TRH secretion as seen in primary and secondary hypothyroidism?
Increased prolactin secretion causing galactorrhea
Where is prolactin secreted from?
Mainly anterior pituitary
Prolactin is structurally homologous to what other hormone?
Growth Hormone (GH)
Libido is associated with excessive amounts of what anterior pituitary hormone?
Prolactin
What is the function of prolactin?
Milk production, inhibit ovulation and spermatogenesis
What hypothalamic hormone is inhibited by prolactin?
GnRH
What dopamine agonist can be used to treat prolactinoma and inhibit prolactin secretion?
Bromocriptine
What is the effect of antipsychotics and estrogens on prolactin secretion?
Stimulate production via dopamine antagonistic effects
How does prolactin inhibit its own secretion?
Increases dopamine release
How does dopamine inhibit prolactin secretion?
Tonic release of dopamine via tuberoinfundibular pathway of hypothalamus
What are the effects on TRH by increasing plasma T3/T4?
Decreased TRH
What are the effects of pregnancy on prolactin release?
Increases estrogen which stimulates prolactin release
What are the effects of spermatogenesis and ovulation on prolactin release?
Increase FSH and LH which inhibit prolactin release
What is the effect of progesterone on prolactin release?
Inhibits prolactin release
What is the effect of nipple stimulation on prolactin release?
Increases prolactin release
What is the effect of a crying baby or sight of a baby on prolactin release?
Inhibits higher cortical centers which inhibit hypothalamic release of dopamine and stimulate TRH release causing prolactin secretion
What is the effect of GH on insulin?
Increases insulin resistance
What hormone is released by liver vi GH stimulation?
IGF-1
What type of release is seen in GH?
Pulsatile release
What is the effect of excess GH release?
Adults - Acromegaly
Children - Gigantism
What is the main cause of excess GH release?
Pituitary adenoma
What is the treatment for acromegaly or gigantism?
Ocreotide or surgery
What inhibits release of GH?
Glucose, somatostatin via negative feedback by somatomedin
When is secretion of GH seen?
Exercise, deep sleep, puberty and hypoglycemia
Sleep deprivation or starvation lead to a decrease of which appetite regulatory hormone?
Leptin
Sleep deprivation and Prader-Willi syndrome lead to an increase of which appetite regulatory hormone?
Ghrelin
Where is leptin made?
Adipose tissue
Where is ghrelin made?
Stomach
What area of the brain is affected by endocannabinoids?
Hypothalamus and nucleus accumbens
What hormone regulates serum osmolarity and blood pressure?
ADH
What ADH receptors regulate serum osmolarity?
V2 receptors
What ADH receptors regulate blood pressure?
V1 receptors
How is osmolarity via ADH regulated?
Insertion of aquaporin channels in in principal cells of renal collecting duct
What ADH levels are seen in central diabetes insipidus?
Decreased ADH levels
What ADH levels are seen in nephrogenic diabetes insipidus?
Normal or increased ADH levels
What type of mutation can cause nephrogenic DI?
V2 receptor mutation
What ADH analog is used to treat central DI and nocturnal enuresis?
Desmopressin acetate
What are the primary regulators of ADH?
Osmoreceptors in hypothalamus
What condition can cause release of ADH?
Hypovolemia
Which antifungal will inhibit cholesterol desmolase?
Ketoconazole
Ketoconazole will inhibit which cholesterol enzyme?
Cholesterol desmolase
What is the rate-limiting step of cholesterol synthesis?
StAR
What enzyme is responsible for the conversion of testosterone to DHT?
5-alpha-reductase
Which drug inhibits 5-alpha-reductase?
Finasteride
The hormonal breast cancer drug, exemestane, will inhibit which enzyme?
Aromatase
Which hormonal breast cancer drugs are known to inhibit aromatase?
Exemestane and anastrozole
What is the only steroid that is not protein bound and is water soluble since it is sulfated?
DHEA
What enzyme, responsible for aldosterone, is acted on by angiotensin II?
Aldosterone synthase
What enzyme in cholesterol synthesis is acted on by ACTH?
Cholesterol synthase
What are common findings in all congenital adrenal enzyme deficiencies?
Increased ACTH, enlarged adrenal glands, decreased cortisol and skin hyperpigmentation
Which enzyme deficiency leads to ambiguous genitalia and undescended testes in men and lack of 2ndary sexual development in girls?
17-a-hydroxylase
What potassium levels are seen in patient with decreased androstenedione and lack of 2ndary sexual development?
Hypokalemia
17-a-hydroxylase deficiency will result in what sex hormone levels?
Decreased
What hormones are produced in excess in 17-a-hydroxylase deficiency?
Mineralocorticoids
What is the most common congenital adrenal enzyme deficiency?
21-B-hydroxylase deficiency
What potassium levels are seen in 21-B-hydroxylase deficiency?
Hyperkalemia
21-B-hydroxylase deficiency results in what mineralocorticoid levels?
Decreased
Precocious puberty and salt wasting seen in infancy with decreased BP is seen in which congenital adrenal enzyme deficiency?
21-B-hydroxylase deficiency
What renin levels are seen in 21-B-hydroxylase deficiency?
Increased renin levels
Hypokalemia, increased sex hormones, high blood pressure and virilization is seen in what congenital adrenal enzyme deficiency?
11-B-hydroxylase
17-a-hydroxyprogesterone is increased in which congenital adrenal enzyme deficiency?
21-B-hydroxylase
What is the effect of Cortisol on hyperglycemia?
Increases gluconeogenesis and insulin resistance
What effects does cortisol have on wound healing?
Decreased inflammatory and immune response
What effects does cortisol have on TB and candidiasis?
Reactivation via blockage of IL-2 production
What effect does chronic stress have on cortisol?
Causes prolonged secretion
How does cortisol increase BP?
Upregulation of alpha-1 receptors on arterioles, increases sensitivity to NE and Epi and can bind to aldosterone receptors at high concentrations
What is the active form of calcium?
Ionized or free calcium
How is calcium found in the body?
Ionized (45%), bound to albumin (40%), and bound to anions (15%)
Cramps, pain, paresthesias, and carpopedal spasms are seen with what electrolyte imbalance?
Hypocalcemia
What causes increased binding of calcium to albumin
Increases in pH
What is the primary regulator of PTH
Ionized/free calcium
What effect do pH changes have on PTH secretion?
Can effect PTH levels based on pH
What effect do changes in albumin levels have on PTH secretion?
None
How does acidosis affect calcium levels?
Increases free calcium which decreases PTH levels
How does alkalosis affect calcium levels?
Decreases free calcium which increases PTH levels
D2 is obtained from what sources?
Ingestion of plants
D3 is obtained from what sources?
Sun exposure and ingestion of plants
Where in the body does vitamin D2 or D3 get converted to 25-OH?
Liver
Where in the body does vitamin 25-OH get converted to 1,25-(OH)2?
Kidneys
What is the active form of vitamin D?
1,25-(OH)2
What is the function of vitamin D?
Increase absorption of calcium and phosphate in gut and enhance bone mineralization
What increases production of 1,25-(OH)2?
Increased PTH and decreased calcium and phosphate
What does vitamin D deficiency cause in children?
Rickets
What does vitamin D deficiency cause in adults?
Osteomalacia
What is the inactive form of vitamin D?
24,25-(OH)2 D3
What is the function of PTH?
Increase calcium reabsorption and decrease phosphate reabsorption in the kidneys
What increases reabsorption of both calcium and phosphate from the gut?
1,25-(OH)2 D3
Where is parathyroid hormone secreted from?
Chief cells of he parathyroid
Where in the renal tubule is calcium reabsorbed?
Distal convoluted tubule
Where in the renal tubule is phosphate reabsorption blocked?
Proximal convoluted tubule
What is the function of PTH
Increase bone resorption of calcium and phosphate
Increase calcium reabsorption at DCT
Increase 1,25-(OH)2 D3 production
Decrease phosphate reabsorption at PCT
What is calcitrol?
1,25-(OH)2 D3, the active form of vitamin D
How does PTH effect serum calcium and phosphate levels?
Increases calcium and decreases phosphate
How does PTH effect urine calcium and phosphate levels?
Decreases calcium and increases phosphate
How does PTH effect urine cAMP levels?
Increases cAMP
What PTH like hormone ins commonly increased in malignancies like squamous cell carcinoma of the lung or renal cell carcinoma?
PTHrP
What is the effect of PTH on osteoblasts and osteocytes?
Stimulates RANK-L
What is the effect of RANK-L on osteoclast activity?
Binds to RANK receptor on osteoclast and increases calcium via bone resorption
What serum calcium, phosphate, and magnesium levels are seen with increased PTH
Decreased calcium, phosphate, and magnesium levels
What is the effect of markedly decreased magnesium levels on PTH?
Decreases PTH
What commonly causes decreases in magnesium levels?
Diarrhea, aminoglycosides, diuretics and alcohol abuse
Where is calcitonin secreted from?
Parafollicular cells (C cells) of the thyroid
What enzyme in the kidney is responsible for converting vitamin D into its active form?
1-alpha-hydroxylase
What serum calcium, phosphate, and magnesium levels cause PTH to be secreted?
Decreased levels
What effect does an increase in 1,25-(OH)2 D3 have on PTH?
Negative feedback, inhibits PTH
What effect does decreased phosphate have on 1-alpha-hydroxylase activity?
Increases activity to make 1,25-(OH)2 D3 which increases calcium and phosphate gut absorption and release from bone
What hormone opposes actions of PTH?
Calcitonin
What effect does calcitonin have on calcium?
Decreases bone resorption of calcium
What effect does increased serum calcium have on calcitonin?
Increases calcitonin secretion
Where is T3 formed mostly?
At target organs
What anterior pituitary hormone functions synergistically with T3/T4?
GH
What is the effect of T3 on the body?
Increased:
- Bone growth and CNS maturation
- B1-receptors in heart = increased CO, HR, SV, contractility
- BMR via increased Na/K/ATPase activity
- Glycogenolysis, gluconeogenesis and lipolysis
How do increased T3/T4 levels effect TRH?
Anterior pituitary - decreased sensitivity to TRH
Hypothalamus - decreased TRH release
How does TRH effect T3/T4?
TRH stimulates TSH release from pituitary which stimulates follicular cells in thyroid to release T3/T4
Effect where excess iodine temporarily inhibits thyroid peroxidase causing decreased iodine organification and production of T3/T4
Wolff-Chaikoff effect
What protein is responsible for binding most T3/T4 in blood?
Thyroxine-binging globulin (TBG)
Which form of T3/T4 is active form?
Unbound form
When are decreased TBG levels seen?
Liver disease and steroid use
When are increased TBG levels seen?
Pregnancy and OCP use
What sex hormone increases TBG?
Estrogen
What enzyme is responsible for the peripheral conversion of T4 to T3?
5’-deiodinase
What thyroid hormone is the major thyroid product?
T4
Which thyroid hormone has a greater affinity for the nuclear receptor in target tissues?
T3
Which enzyme is responsible for oxidation, organification of iodide and coupling of MIT and DIT?
Thyroid peroxidase
T4 is composed of what two molecules?
2 DIT molecules
T3 is composed of what two molecules
1 DIT + 1 MIT
Which drug inhibits both thyroid peroxidase and 5’-deiodinase?
Propylthiouracil (PTU)
Which drug inhibits only thyroid peroxidase?
Methimazole
What effect do glucocorticoids have on thyroid hormone production?
Inhibit peripheral conversion of T4 to T3
Which endocrine hormones are associated with cAMP?
FLAT ChAMP:
FSH, LH, ACTH, TSH, CRH, hCG, ADH, MSH, PTH
calcitonin, GHRH, glucagon, histamine
Which cAMP associated endocrine hormones have V2 receptor binding?
FSH, LH, ACTH, TSH, CRH, hCG, ADH
Which cAMP associated endocrine hormones have H2 receptor binding?
MSH, PTH, calcitonin, GHRH, glucagon, histamine
Which endocrine hormones are associated with cGMP?
BAD GraMPa (think vasodilators): BNP, ANP, EDRF
Which endocrine hormones are associated with intracellular receptors?
PET CAT on TV:
Progesterone, Estrogen, Testosterone
Cortisol, Aldosterone, T3/T4, Vitamin D
Which endocrine hormones are associated with receptor tyrosine kinase?
MAP kinase pathway (think Growth Factors):
insulin, IGF-1, FGF-1, PDGF, EGF
Which endocrine hormones are associated with non-receptor tyrosine kinase?
JAK/STAT pathway (PIGGLET) acidophils and cytokines:
Prolactin, Immunomodulators, GH, G-CSF, Erythropoietin, Thrombopoietin
What binding hormone causes gynecomastia in men?
Increased sex-hormone binding globulin
What binding hormone causes hirsutism in women?
Decreased sex-hormone binding globulin
What hormone binds testosterone?
Sex-hormone binding globulin
What condition in women increases sex-hormone binding globulin?
OCPs and pregnancy
