Lecture 1 - 3: Physiology (Also Pharm Lectures) Flashcards
Endocrine communication
release of a chemical transmitter (hormone) by specialized cells; carried to a distant site of activation via the blood
Neuroendocrine communication
hybrid of neural and endocrine communication; release of “neurohormone”; carried to a distant site of action via blood
Paracrine communication
cells secrete chemical transmitters locally; the target cells are near “neighbors” and are reached by diffusion of the hormone
Autocrine
cell regulates itself by release of a chemical messenger
Protein/Peptide hormones
largest group
post-translationally processed to active hormone
released via exocytosis from secretory granules
Steroid hormones
derived from cholesterol
synthesized by adrenal cortex, testes/ovaries, placenta
lipid-soluble, travel bound to binding proteins
bind to cytosolic or nuclear receptors
Amines/Amino acid derivative hormones
derived from tyrosine
norepi, epi, dopamine, thyroid hormones
What are hormones made out of?
Proteins/peptides
steroids
amines/amino acid derivatives
Peptide hormones
water soluble does NOT use carrier protein in plasma stored in vesicles prior to secretion mainly secondary messengers FAST onset but short acting response receptors on the plasma membrane
Steroid Hormones
not water soluble need carrier protein in plasma not stored in vesicles intracellular receptors mainly altered gene expression slow onset but long-lasting responses
Which type of hormones have the longest acting response?
Steroid
slower onset
Which type of hormone class is water soluble?
peptide
Which type of hormone class is stored in vesicles?
peptide
Corticotropic-releasing hormone (CRH)
hypothalamus
peptide hormone
stimulates adrenocorticotropic hormone (ACTH)
ACTH
secreted from anterior pituitary
peptide hormone
trophic to adrenal cortex
stimulates synthesis and secretion of cortisol, aldosterone, and androgens
How can you have an abnormal function of hormones?
- excess of deficiency of hormone (genetics, agonists, antagonists)
- decreased receptor number (genetics, downregulation)
- decreased receptor function (genetics, pathophysiologial)
What affects the half life of hormones?
protein binding can increase half life and delay onset of action
metabolism
number or receptors available
clearance
The plasma free hormone concentration is affected by:
rate of secretion
rate of elimination (excretion + metabolism)
extent of hormone binding to plasma proteins
Hormone release may oscillate relative to:
circadian rhythms
in response to timing of meals
as regulated by other pattern generators
you can’t take a snapshot of hormone levels –have to watch it overtime
Why do we have growth hormone?
linear growth in growing ages
maintain lean body mass in adult
highest in puberty but still present in adulthood
What hormones are produced in the adrenal cortex?
corticosteroids
mineralocorticoids
androgens
What hormones are produced in the adrenal medulla?
epi
norepi
Where is cortisol secreted?
in the zona fascilculata in the adrenal cortex
Conn syndrome
primary aldosteronism
excess secretion of aldosterone due to adrenal disease
K+ depletion
Na+ retention
HTN
Secondary aldosteronism is dependent on what?
renin
What inhibits synthesis of steroids?
Ketoconazole
Metyrapone
Mitotatane (kills adrenal cortical cells)
What are the effects of growth hormone?
1) uses fat (increase in free fatty acid uptake by cells via increases LDL receptors, so cells use fatty acid for energy)
2) saves glucose for brain (hyperglycemia d/t no glucose being absorbed by cells)
3) builds muscle (decrease plasma AA)
What are the effects of Insulin?
STORAGE
1) increase fat storage by increasing VLDL in liver
2) decrease plasma glucose (increase glycolysis and glycogen production)
3) builds muscle (decrease plasma AA)
What is the GH Axis?
hypothalamus releases GHRH which stimulates the pituitary which releases GH which stimulates many things including the liver which produces IGF1 which negatively feeds back to the pituitary
What does IGF1 do?
used in fetal production (as well as normally in adulthood)
- stores fat
- decreases plasma glucose
- builds muscle (builds muscle better when with GH)
causes growth proliferation and apoptosis suppression in visceral organs, cartilage, bone, skin, and muscles (risk of tumor production)q
What are the different causes of increased GH production?
pituitary adenoma
ectopic tumor producing GH (lymphoma)
ectopic tumor producing GHRH (small cell carcinoma)
What labs would you expects to see with someone who has a pituitary adenoma?
high GH
possibly high PL
low every other hormone from the anterior pituitary
What is the difference between adults and children with excessive GH?
children - giantism
adults - acromegaly
both end up with type 2 DM d/t increase insulin and glucose and insulin resistance
What will you see in people with GH deficiency?
kids - dwarfism
adults -
fatigue, obesity, decrease in muscle mass, increase in LDL, decrease in heart function
How do you dx insulin deficiency?
in a non DM pt – given insulin and then check GH — a normal person would have increase GH in response to decrease in glucose
in a DM pt - give GHRF and arginine IV
expect to see GH increase in normal person
How do you measure GH level?
better to measure it indirectly via IGF1 since GH fluctuates throughout the day
How do the cells in islets of langerhan communicate?
gap junctions
What do alpha cells in the pancreas produce?
glucagon
Where is insulin produced?
beta cells in pancreas
What do delta cells in the pancreas produce?
somatostatin
Why is glucose control so important?
damage cells if too high
How does insulin get released?
via GLUT2 transporter
glycolysis produces ATP that blocks K+ channels, depolarizing the membrane and causing an influx of Ca2+ which stimulates insulin release (Ca2+ stimulated exocytosis)
What are stimulants of insulin release?
glucose fatty acids hormones (incretins, secretin) parasympathetic stimulation B2 agonist
Incretins
released from intestine cells to stimulate pancreas to release insulin
What are inhibitors of insulin?
sympathetic stimulation (although it stimulates beta 2 receptors it inhibits alpha receptors causing an overall inhibitory effect)
somatostatin
insulin (neg feedback)
beta antagonists
GLUT4
insulin promotes relocation of this transported to the membrane of muscle and fat cells
What happens when you have chronic insulin activation?
receptor internalization and down regulation of response
What is insulins effect?
Seconds:
- AA uptake
- glucose uptake
Minutes:
- activation of glycolytic enzymes, glycogen synthase, lipid signaling
- inhibits glycogen phosporylase and glyconeogenesis
Hours:
- gene transcription
- cell growth differentiation
What stimulates glucagon?
hypoglycemia
epinephrine
vagal stimulation
What inhibits glucagon?
hyperglycemia
somatostatin
What do catecholamines do to glucose and insulin?
increase blood glucose
inhibit insulin secretion
What do glucocorticoids and GH do to glucose and insulin?
increase blood glucose
decrease insulin sensitivity
What stimulates somatostatin?
glucose
AA
fatty acids
Where in the body is the bulk of glucose taken up?
skeletal muscle
Adipokines
adipose tissues release this hormone to aide in insulin’s effect
Leptin
made in fat (levels vary based on how much fat a person has)
works in the brain to decrease appetite
the body becomes desensitized to leptin once you become too fat
How can excessive exercise in a DM pt precipitate hypoglycemia?
exercise increases the # of GLUT4 transporters on the skeletal muscle cells increasing the about of insulin that can bind and allow glucose into the cells
