exam 2b Flashcards
Describe the adrenal glands.
Small, triangular positioned above kidneys.
How much does each adrenal gland weigh?
4-6 g in adult
How much of adrenal gland does outer cortex occupy?
80-90%
What are the five layers of the adrenal gland?
From inside, medulla, zona reticularis, zona fasciculate, zona glomerulosa, capsule
What hormones does medulla secrete?
Epinephrine and norepinephrine
Name of cells in medulla?
Chromaffin cells and ganglion cells
What blood vessels do we see in medulla histology?
Medullary veins
What do zona reticularis and zona fasciculata secrete?
Glucocorticoids and gonadocorticoids
What does zona glomerulosa secrete?
Mineralo-corticoids
How is the adrenal medulla part of the CNS?
It is a modified sympathetic ganglion with postganglionic cells, but no axons, that is specialized to secrete catecholamines from chromaffin cells.
Catecholamines?
Epinephrine and norepinephrine
Synthesis of catecholamines cycle
Start with tyrosine tyrosine hydroxylase in cytoplasm dihydroxyphenylalanine (Dopa) aromatic L-amino acid decarboxylase in cytoplasm dopamine dopamine beta-hydroxylase in granule norepinephrine phenylethanolamine N-methyltransferase in cytoplasm epinephrine enters granule
What are the major actions of epinephrine?
Stress/arousal response, metabolic action and cardiovascular action
How do catecholamines affect sugar metabolism?
Inhibit insulin. Stimulate glucagon.
How does stimulation of glucagon affect glucose metabolism?
In adipose tissue, stimulates lypolysis, which increases free fatty acids. In liver, stimulates keto-genesis, which increases ketones, stimulates glycogenolysis and gluconeogenesis, which upregulate glucose. Muscle undergoes glycogenolysis and increases lactate, which liver uses to make glucose.
How do epinephrine levels react to hyperglycemia induced by insulin?
Rise 50 fold in normal human subjects.
How do catecholamines react to swimming at 37, 33 and 21 degrees Celsius?
At 37 degrees, levels of epi and norepi are the lowest, reaching peak at about 60 minutes. At 33 degrees, second lowest. At 21, highest, due to stress of cold temperature. Thermogenesis.
Describe beta-adrenergic receptor
G protein coupled 7TM domain receptor with ligand binding region buried in lipid bilayer. N terminus outside. C terminus in cytosol.
Epinephrine signaling cascade
epinephrine to adenylyl cyclase, cAMP, PKA, enzyme activated, product
Adrenergic receptors: what G protein do alpha 1 and M1 receptors couple with?
Gq
What does Gq stimulate?
phospholipase C
What does phospholipase C bind?
PIP2 in plasma membrane, which activates IP3/DAG pathway
What does DAG activate?
protein kinase C
What does IP3 do?
upregulates cytosolic calcium from endoplasmic reticulum.
What does Ca2+ do in IP3/DAG pathway?
binds calmodulin, which activates a protein kinase
Gq pathway?
phospholipase C / PIP2 / IP3/DAG pathway / IP3 upregulates calcium in cytosol / DAG activates protein kinase C / calcium binds calmodulin which activates protein kinase
What G protein do alpha2, M2 and DA2 couple with?
Gi
Gi pathway?
inhibit adenylyl cyclase, inhibit cAMP, inhibit PKA
What G protein do beta1, beta2, beta3 and DA1 couple with?
Gs
Gs pathway?
stimulate adenylyl cyclase, upregulate cAMP, activate PKA
Functions of alpha receptor (6)
vasoconstriction, iris dilatation, intestinal relaxation, intestinal sphincter contraction, pilomotor contraction, bladder sphincter contraction
Functions of beta receptors
beta1 – cardioacceleration, lipolysis, increased myocardial strength/ beta2 – vasodilatation, intestinal relaxation, uterus relaxation, bronchodilatation, calorigenesis, glycogenolysis and bladder wall relaxation
General function of beta receptor
relaxation of tissue
Which adrenergic receptor is dominant to epinephrine? Which is silent?
alpha receptor, which leads to smooth muscle contraction in physiological experiment. Beta receptor is silent.
How can one reverse receptor dominance of catecholamines?
use an alpha receptor blocker to make alpha receptor silent and activate beta receptor, which relaxes smooth muscle
Practolol
beta1 antagonist
Butoxamine
beta2 antagonist
Prenalterol
beta1 agonist
Salbutamol
beta2 agonist
Isoproterenol
beta adrenergic antagonist
How does epinephrine compete against analogues alprenolol and isoproterenol in binding to liver receptors?
alprenolol and isoproterenol are more competitive
How do beta blockers work with catecholamines?
if no blockers, full catecholamine stimulation of receptors. If beta blocker without agonism, no stimulation. If beta blocker with partial agonism, weak stimulation.
Three types of adrenergic agonists
direct-acting, mixed-acting, indirect-acting
What are the two types of direct-acting adrenergic agonists?
selective and non-selective
Example of indirect-acting releasing agents
amphetamine, tyramine
Example of indirect-acting uptake inhibitor
cocaine
How do epi and norepi affect the isolated heart? What receptors mediate the responses?
they increase the force and rate of contraction of the isolated heart. Responses mediated by beta1 receptors.
How does norepi affect blood vessels?
produces vasoconstriction in most if not all organs via alpha 1 receptors
How does epi affect blood vessels?
dilates the blood vessels in skeletal muscle and the liver via beta2 receptors
How does vasodilation by epi affect vasoconstriction elsewhere?
overbalances vasoconstriction by norepi and total peripheral resistance drops
What happens when norepi is infused slowly in humans?
systolic and diastolic bp rise, which causes hypertension
What does hypertension stimulate?
carotid and aortic baroreceptors, producing reflex bradycardia that overrides direct cardioacceleratory effect of norepi. Cardiac output thus falls.
How does epi affect pulse pressure?
causes a widening of pulse pressure, but because baroreceptor stimulation is insufficient to obscure the direct effect of the hormone on the heart, cardiac rate, and output increase.
2 ways to treat hypertension
lifestyle modifications and medication
what is “not at goal bp”?
<130/80 mmHg for patients with diabetes or chronic kidney disease
ACEI
angiotensin converting enzyme inhibitor
ARB
angiotensin receptor blocker
BB
beta-blocker
CCB
calcium channel blocker
Potential sites of action for antihypertensive drugs
CNS, heart, blood vessels, kidney
Antihypertensive drugs for CNS
beta blockers, alpha2 agonists
Antihypertensive drugs fro heart
beta blockers
Antihypertensive drugs for blood vessels
alpha1 receptor blockers, calcium channel blockers, vasodilators, AT1 receptor antagonists, ACE inhibitors
Antihypertensive drugs for kidneys
diuretics, beta blockers, ACE inhibitors
Concept of receptor desensitization
at high concentration of hormone the physiological response may be lower than at lower concentration
How can desensitization be achieved?
by modification of receptor to decrease optimal response (phosphorylation)
How can receptor number be decreased?
internalization via endocytosis
What does p53 respond to?
DNA damage, cell cycle abnormalities, hypoxia
What does p53 lead to?
cell cycle arrest or apoptosis
Cell cycle arrest pathway
cell cycle arrest/DNA repair/cell cycle restart/cellular and genetic stability
Apoptosis pathway
death and elimination of damaged cells/cellular and genetic stability
Uses of beta-antagonists in clinical medicine
to decrease cardiac output to treat hypertension an congestive heart failure; to treat migraine headache and stage fright; to treat PTSD
Use of beta agonist in clinical medicine
to dilate bronchi in asthma
Use of natural catecholamine in clinical medicine
to increase bp and increase heart rate
Use of epi in clinical medicine
to treat allergic reaction
What is pheochromocytoma?
tumor of adrenal gland. Benign but secretes lots of catecholamines.
Symptoms of pheochromocytoma?
high bp, tachycardia, palpitations, sweating, tremors, nervousness, weight loss and hyperglycemia
Detection of pheochromocytoma?
measure levels of catecholamines in blood or degradation products in urine. CT scan for adrenal tumors.
