Endo General Flashcards
What are steroids derived from
cholesterol
What are amines/AA derived from?
tyrosine
peptide hormone receptor location at target cell
plasma mem
steroid hormone receptor location at target cell
intracellular
peptide hormone speed of action
fast onset
steroid hormone speed of action
slow onset
Corticotropin-releasing hormone (CRH) is released from what gland?
fn?
hypothalamus
Fn: Stimulates adrenocorticotropic hormone (ACTH)
ACTH is released from what gland?
fn?
Anterior pituitary
Fn: Stimulates synthesis and secretion of cortisol, aldosterone, and androgens
Antidiuretic hormone (ADH) (also called arginine vasopressin, or AVP) is released from what gland?
fn?
Posterior pituitary
Fn: Increases water retention at kidney, vasoconstricts arterioles
Oxytocin is released from what gland?
fn?
Posterior pituitary
fn: Stimulates uterine contractions during labor, milk ejection in lactation
Aldosterone is released from what gland?
fn?
Adrenal cortex
Fn: Decreases urinary Na+ excretion, Increases urinary K+ and H+ excretion
Cortisol is released from what gland?
fn?
Adrenal cortex
Fn: Released in response to stress, Multiple metabolic actions
Insulin (β cell) is released from what gland?
fn?
Pancreas
Fn: Promotes storage of glucose as glycogen in liver and muscle
Promotes uptake of glucose and storage as triglyceride in adipose tissue and liver
Hormones circulate at (low/high) levels and bind to receptors with (low/high) affinity
Hormones circulate at LOW levels and bind to receptors with HIGH affinity
Hormone generally (can/cannot) cross cell membrane via diffusion
Hormone generally CANNOT cross cell membrane via diffusion
↑ receptor number when hormone level is low
Upregulation
when hormone level is high and/or continuous
Downregulation or desensitization
The plasma free hormone concentration is affected by:
- The rate of hormone secretion
- The rate of hormone elimination
- The extent of hormone binding to plasma proteins
What are the Trophic hormones?
GH: Growth Hormone ACTH: Adrenocorticotropic Hormone LH: Luteinizing Hormone FSH: Follicle Stimulating Hormone TSH: Thyroid Stimulating Hormone PRL: Prolactin
What hormone stimulates release of pancreatic enzymes and where is it released from?
Cholecystokinin (CCK) from Small Intestine
Where is GH produced & released?
anterior pituitary
What are the most abundant cells in the anterior pituitary?
somatotrophs
What is the MC pituitary cell to become malignant
somatotrophs
What do malignant somatotrophs produce?
GH & PRL
What occurs due to growth of a pituitary adenoma?
compresses infundibulum decreasing hypothalamic hormonal stimulation of anterior pituitary hormone release but also decreasing anterior pituitary hormones due to inability to suppress
How do GHRH neurons regulate GH production?
Positive feed-forward regulation
GHRH is released into hypo-physeal portal system and transported to somatotrophs causing GH release to secondary capillary plexus and to the body of the anterior pituitary
How is GH regulated by hypothalamic somatostain neurons?
Negative feed-forward regulation
Somatostain is released into hypophyseal portal system goes to somatotrophs and inhibits GH release
Fn of GH
Linear growth (soft tissue, visceral organ, muscle & bone) in growing ages Maintains lean body mass in adulthood
What is fetal growth mediated by?
IGF1 and IGF-2
How does GH work?
utilizes fat as main energy source
maximizes protein deposition for lean body mass
marks glucose for use by the brain
What contains the greatest number of GH receptors?
liver and cartilage
What is the effect on insulin when GH acts on fat and causes lipolysis and increased FA release?
antagonistic to insulin
GH action on AA
maximize AA and protein for lean body mass production
What is GH action on glucose metabolism?
antagonistic (so blood glucose levels increase)
What happens when there is excessive chronic GH release?
there is sustained increase in plasma glucose causing an increase in insulin and eventually insulin resistance and diabetogenesis
What causes GH excess?
pituitary adenoma
extrapituitary GH excess
excess GHRH
What hormones are secreted from the adrenal cortex?
corticosteroids
mineralocorticoids
androgens
What hormones are secreted from the adrenal medulla?
epinephrine
NE
What regulates glucocorticoid synthesis?
episodic secretion and circadian rhythm of ACTH
stress responsiveness of HPA axis
FB inhibition by cortisol on ACTH sectretion
When are ACTH burst most frequent?
in the AM
What are the physiological actions of glucocorticoids?
maintain blood glucose levels during fasting (increase during stress) by increasing liver synthesis of glucose and glycogen deposition
calcium homeostasis by slowing bone growth and inducing bone demineralization
What is the effect of glucocorticoids on: CV system Skeletal muscls CNS Immune system
CV: HEN with prolonged levels
Skeletal muscle: wasting with prolonged high levels
CNS: either excess fo insufficiency will cause alterations in mood, behavior and excitability
Immune: secreted in response to stress
What prevents glucocorticoids from interacting with the mineralocorticoid receptor?
11β-HSD2 will turn cortisol into cortisone so only the aldosterone can interact witht the MR
MR binds to cortisol with (high/low) affinity. MR target tissues express 11-betaHSD2 which (inactivates/activates) cortisol.
HIGH
INACTIVATES
What is the most active androgen?
testosterone
What is the consequence of 21-Hydroxylase deficiency?
Decreased cortisol and aldosterone
Hypoglycemia because of low cortisol
Loss of sodium because of mineralocorticoid deficiency Virilization because of excess androgen production
What is the consequence of 11β-Hydroxylase deficiency?
Excess mineralocorticoid activity
Hypoglycemia because of low cortisol
Salt and water retention
What is the consequence of 11β-HSD2 deficiency?
Decrease in glucocorticoid inactivation in mineralocorticoid- sensitive cells leading to excess mineralocorticoid activity
ACTH dependent causes of cushings
ACTH secreting tumors
CRH secreting tumors
ACTH independent causes of cushings
glucocorticoid secreting tumors
Causes of addison’s disease
primary adrenal insufficiency due to destruction of adrenal cortex
both mineralocorticoid and glucocorticoid deficiency
What is effect of Mifepristone at high doses on Glucocorticoid Function?
blocks the glucocorticoid receptor, blocks feedback regulation of HPA, increases ACTH and cortisol but blocks the action of cortisol at the receptor
What is effect of Spironolactone and Eplenerone at on Mineralocorticoid Function?
Inhibits binding of aldosterone to the MR
What is secreted from zona glomerulosa layer of adrenal cortex?
Mineralocorticoids
Aldosterone, deoxycorticosterone
What is secreted from zona fasiculata layer of adrenal cortex?
Glucocorticoids
Cortisol, corticosterone
What is secreted from zona reticularis layer of adrenal cortex?
Sex Steroids
Androgen
What is the precursor for adrenal steroidogenesis?
cholesterol
What is the principal hormone that stimulates adrenal glucocorticoid synthesis and secretion and where is it syntehsized?
ACTH synthesized in the anterior pituitary
What controls POMC secretion which leads to the production of ACTH?
CRH
Argininevasopressin
Endogenouscircadianrhythm
What causes hyperpigmentation in primary AI?
increased production of POMC which produces melanocyte stimulating hormone in addition to ACTH
What does TH do?
Maintains level of metabolism in tissues optimal for normal function
What happens if fetus/neonate has thyroid hypofn?
results in mental retardation and dwarfism
What happens if adult has thyroid hypofn?
mental and physical slowing, poor resistance to cold; adult hyperthyroidism-body wasting, nervousness, tachycardia, tremor, excess heat production
Effect of TH on heart
Increased number of beta-adrenergic receptors
Effect of TH on adipose tissue
Stimulated lipolysis
Effect of TH on muscle
Increased protein breakdown
Effect of TH on bone
Promote normal growth and skeletal development
Effect of TH on nervous system
Promote normal brain development
Effect of TH on gut
Increased rate of carbohydrate absorption
Effect of TH on lipoprotein
Formation of LDL receptors
What cells secrete thyroid hormones, which are critical to development, growth and metabolism?
Follicle cells
What cells secrete calcitonin, which regulates circulating levels of calcium
Parafollicular cells
What is minimum daily intake of iodine recommended for normal adult thyroid fn?
150 ug/d
Deiodination is dependent on what?
P450
What is conserved with a decline in T3?
calories and protein
What happens to the thyroid if you remove the pituitary?
gland atrophies
What happens to the thyroid if you administer TSH?
thyroid fn is stimulated
if prolonged will become a goiter
What is Wolff-Chaikoff effect?
large doses of iodine inhibit organification and metabolic activity of the thyroid gland is decreased
What is NIS?
sodium iodide symporter
What happens to TH receptors during starvation?
decreased number of receptors
Thyrotoxicosis
thyroid hormone excess
Hyperthyroidism
excessive thyroid function
What is the MC thyroid abnormality?
goiter
Causes of goiter
Iodide deficiency
Hashimoto’s (aka chronic lymphocytic thyroiditis or autoimmune thyroiditis)
Grave’s disease
When do sx of hypoglycemia develop in healthy individuals?
<55 mg/dl
Name the only endogenous steroid inhibiting ACTH
Cortisol (synthetics also suppress)
What do Extraadrenal ganglia produce?
NE
What does adrenal medulla produce?
epi
Innermost concept of self as
male, female, a blend of both or neither
Gender Identity
External appearance of one’s gender expressed through behavior, clothing etc.
Gender Expression
Who you like, desire, are attracted to
Sexual Orientation
What cells make up the majority of the islets of langerhans?
Beta cells (which secrete insulin)
What do alpha cells in islets of langerhans secrete?
glucagon
What do beta cells in islets of langerhans secrete?
insulin
What do delta cells in islets of langerhans secrete?
somatostatin
What do F(PP) cells in islets of langerhans secrete?
pancreatic polypeptide
Fn of insulin
energy conservation-directs fuel metabolism to CHO use
DECREASES blood glucose concentration
Fn of glucagon
energy use
INCREASES BG concentration
What is insulin’s halflife?
5 min
What stimulates insulin release?
glucose, GLP1 and GIP
parasym stimulation
Beta 2 adrenergic receptor agonists
Biphasic effect of sympathetic stil
inhibition via alpha 2 and stimulation via beta2
Overall effect is INHIBITORY
What occurs as a result of insulin signaling?
cell growth, differentiation, survival, protein synthesis, glycogen syntehsis, metabolic pathways
What occurs in muscle and fat tht lowers blood glucose?
insulin promotes relocalization of GLUT4 transporter to cell mem
GLUT 2 Fn
Regulation of insulin release
GLUT 4 Fn
Insulin-mediated glucose uptake
found primarily in adipose tissues and striated muscle (skeletal and cardiac)
What occurs as a result of chronic activation of insulin receptor?
causes receptor internalization & down- regulation of response
Glycolysis
breakdown of glucose
Gluconeogenesis
generation of glucose
Glycogenolysis
breakdown of glycogen into glucose
Glycogenesis
formation of glycogen
What does somatostatin do?
inhibits everything
Effect of glucagon on:
glucose
FA
ketoacids
Increases them all
What hormones increase BG besides glucagon?
catecholamines- fast when SEVERELY hypoglycemic or stress
glucocorticoids- slow when stress, prolonged fasting or hypoglycemia
GH- slow when fsating, sleep or stress
epi, NE and dopamine
catecholamines
Effect of catecholamines on:
insulin secretion
glycogenolysis
gluconeogenesis
Inhibits insulin secretion
Stimulates glycogenolysis
Stimulates gluconeogenesis
Effect of glucocorticoids on:
insulin secretion
glycogenolysis
gluconeogenesis
Reduces insulin sensitivity
Does NOT stimulate glycogenolysis
Stimulates gluconeogenesis
Effect of GH on:
insulin secretion
gluconeogenesis
Reduces insulin sensitivity (decreases glucose uptake)
Stimulates gluconeogenesis
What stimulates somatostatin release and what is its effect?
stimulated by glucose; amino acids; fatty acids
Inhibitory effect on virtually all gastrointestinal and pancreatic exocrine and endocrine functions.
Why is somatostatin’s effect on insulin and glucose limited?
it is produced in delta cells which are in the periphery of islet and the blood flows from the center first then to the periphery
What is the effect of pancreatic polypeptide?
antagonizes CCK and inhibits gallbladder contraction and decreases GI motility
Why does insulin resistance occur as fat increases?
fat cells synthesize and release hormone signals (adipokines) that antagonize insulins effects on target cells
What adipose signal can aid in insulins effects?
Leptin
Fn of leptin
Acts in brain to lower appetite
What is the effect of exercise on glucose and insulin?
↑ glucose entry into skeletal muscle
insulin-independent ↑ in the number of GLUT-4
transporters
Can precipitate hypoglycemia in diabetics
What does a 1% change in HbA1c do to plasma glucose
29 mg/dl change in average plasma glucose
What is a strong predictor of cardiovascular disease in patients with type 2 diabetes?
Microalbuminuria
Effect of PTH
increase bone reabsorption, inc ca and Cl and decrease PO4 and HCO3-
Effect of calcitriol (1,25-OH)2 vit D
increase Ca, PO4 abs
What is recommended daily vit D intake?
Children, adults, pregnancy, lactation- 600 IU
> 70- 800 IU
What is optimal vit D levels?
20-60 ng/ml
What is the active form Vit D?
1,25 (OH) vitamin D
What cells produce T4 and T3?
Follicular cells
Colloid represents
stored thyroid hormone
