[M6] Part 3.2: Adrenal Gland (medulla) Flashcards
Inner adrenal gland composed of chromaffin cells
ADRENAL MEDULLA
ADRENAL MEDULLA Inner adrenal gland composed of chromaffin cells that secretes the hormone, _____
catecholamines
For adrenal medulla to secrete/produce
catecholamine, it require its ____
precursors
What are the two precursors of adrenal medulla
→ Phenylalanine
→ Tyrosine
Phenylalanine and Tyrosine are ___
amino acids
Catecholamines are named catecholamines
because of its ____
structure
What is/are present in Catecholamine structure?
Catechol nucleus;
Amine side chain
benzene with 2 hydroxyl side group
Catechol nucleus
Catechol nucleus is a ___ with ___ hydroxyl
side group
benzene ;
2
Chromaffin cells are derived from ____
neural crest
neural crest is specifically known as:
primordial neural crest (PNC)
Refers to the group of hormones synthesized by
chromaffin cells of the adrenal medulla
CATECHOLAMINES
What are the 3 common catecholamines
Epinephrine, Norepinephrine, and
Dopamine
What are the functions of CATECHOLAMINES
● 1st responder to stress
● Promotes fight-or-flight response
● Dilate pupils
One of the functions of catecholamine is that it Promotes fight-or-flight response because catecholamines:
→ ____ (Inc/dec) ____ output and ____
→ Diverts ____ toward ___ and ____
→ Mobilizes ___ from ___ (releasing ___)
→ Increases ; cardiac ; blood pressure
→ blood ; muscle ; brain
→ fuel ; storage ; glucose
DEVELOPMENT OF MEDULLA:
- At the early stage of ____ , ___ will go to
____ region
gestation ;
Primordial Neural Crest (PNC);
thoracic
DEVELOPMENT OF MEDULLA:
- A few weeks after, majority of ___ will migrate to
____ to form ___
PNC ;
Adrenal cortex ;
Adrenal Medulla
What are the 2 cells that arises from the neural crest?
Sympathogonia
Pheochromoblast
sympathetic ganglion cells
Sympathogonia
Type of tumor that may arise in Sympathogonia
Sympathoblasts
childhood tumor
Sympathoblasts
rarely seen among adolescence
Sympathogonia
Type of tumor that arises from ganglion cells
Sympathoblasts
Sympathoblasts secretes _____
Homovanillic Acid (HVA)
Examples of Sympathoblasts
Malignant neuroblastoma
Benign ganglioneuroma
medulla chromaffin cells
Pheochromoblast
seen in adrenal medulla
Pheochromoblast
Type of tumor that may arise in Pheochromoblast
Pheochromocytoma
Pheochromocytoma secretes?
catecholamines
Type of tumor that arises from chromaffin cells
Pheochromocytoma
Pheochromocytoma Has the ability to migrate towards ____, forming _____
AORTA ;
paraganglia
BIOSYNTHESIS OF CATECHOLAMINES
- In cytoplasm
● To synthesize catecholamine, ____ (_____, specifically, ____)
are required
precursors;
phenylalanine and tyrosine ;
tyrosine
Phenylalanine should be converted to _____
tyrosine
immediate/ direct precursor
Tyrosine
T/F: Tyrosine is an immediate/ direct precursor meaning it will
not be converted anymore
T
● Conversion of phenylalanine to ___ to ___ to ___ occurs in the ___
tyrosine
DOPA ;
Dopamine ;
cytoplasm
BIOSYNTHESIS OF CATECHOLAMINES
- In cytoplasm
Once dopamine is synthesized, it will be transported
into a ___ via a transporter called as ____
lipid vesicle ;
VMAT (Vesicular Monoamine Transporter)
BIOSYNTHESIS OF CATECHOLAMINES
- In the lipid vesicle
● ____ inside the lipid vesicle will be converted to ____
● ____ will be released out of the lipid
vesicle, going to the ___
Dopamine ; Norepinephrine (NE)
Norepinephrine ; cytoplasm
BIOSYNTHESIS OF CATECHOLAMINES
- In cytoplasm
● Norepinephrine in the cytoplasm will be converted to
____ by the enzyme _____
● The synthesized/converted ____ will be
____ into a _____ by ____
● Epinephrine (EPI) ; PNMT (Phenylethanolamine N-methyltransferase)
● Epinephrine ; transported ; secretory vesicle ; VMAT
PNMT - is _____ dependent
cortisol
BIOSYNTHESIS OF CATECHOLAMINES
- In the secretory vesicle
● ____inside the secretory vesicle will be
released from the cell through the process called
_____
Epinephrine ;
exocytosis
secretory vesicle attaches to the
cell membrane and will form vacuole to release
the content outside the cell
Exocytosis
BIOSYNTHESIS OF CATECHOLAMINES
- In the circulation
● ____ of ___ will be bound to ____
50%
epinephrine
protein
When will Adrenal Medulla release synthesized
epinephrine?
● Synthesized Epinephrine will be released if there is
a stimulation
T/F: Without stimulation Synthesized Epinephrine will STILL be released
F; it will not be released
Too much epinephrine in the body will result in
___ and ____
tachycardia
high blood pressure
Without ____, catecholamine will be
metabolized in the cytoplasm by the enzyme
_____
nerve stimulation;
catechol-O-methyltransferase
Epinephrine will be metabolized to ___
Metanephrines
Norepinephrine will be metabolized to ___
Normetanephrines
Dopamine will be metabolized to ___
Methoxytyramine
The metabolized catecholamines can be oxidized to ____ by the enzyme ____
Vanillylmandelic Acid (VMA) ; monoamine oxidase
T/F: Once catecholamine become metabolites, it can now
be discarded
T
Why catecholamine should be metabolized before discarding?
Once released catecholamine in the cytoplasm is discarded and goes to ____ , it will stimulate ___(inc/dec) ___ and ___
circulation;
increase ;
cardiac output ;
hypertension
What are the 4 metabolites present in urine?
○ Vanillylmandelic Acid (VMA)
○ Metanephrines
○ Free Norepinephrines
○ Conjugated Norepinephrines
Vanillylmandelic Acid (VMA) is present in urine in what %
30%
Metanephrines is present in urine in what %
20%
Free Norepinephrines is present in urine in what %
5%
Conjugated Norepinephrines is present in urine in what %
(8%
Catecholamines are synthesized by the adrenal
medulla in a ____ ratio of ___
NE:EPI
9:1
T/F: It is normal that more NE is produced than EPI
T
A condition wherein there is an Adrenal insufficiency
Addison’s Disease
A condition wherein there is a ↓cortisol and aldosterone
Addison’s Disease:
In Addison’s dse, there is ↓cortisol and aldosterone. Since ____ is needed by the enzyme ____ thus ___ can’t be converted to ___
Cortisol
PNMT
NE
EPI
an enzyme that converts NE to EPI
PNMT
NE:EPI ratio for FEMALE in Addison’s dse
NE:EPI = 45:1
NE:EPI ratio for MALE in Addison’s dse
NE:EPI = 24:1
Produced by sympathetic ganglia
Norepinephrine
how many % of Norepinephrine is produced by the sympathetic ganglia
98%
how many % of Norepinephrine is produced by adrenal medulla
2%
Highest concentration of Norepinephrine is found in the___
brain
acts as a neurotransmitter for both CNS
and sympathetic nervous system
Norepinephrine
Norepinephrine acts as a neurotransmitter for both ___ and ___
CNS
sympathetic nervous system
2 Metabolites of Norepinephrine
3-methoxy-4-hydroxyphenylglycol (MHPG)
Vanillylmandelic acid (VMA)
the Metabolite of Norepinephrine that is found in both urine and CSF
3-methoxy-4-hydroxyphenylglycol (MHPG)
3-methoxy-4-hydroxyphenylglycol (MHPG) is Found in both ___ and ___
urine
CSF
Epinephrine is aka
“adrenaline”
aka “adrenaline”
Epinephrine
Most abundant medullary hormone
Epinephrine
2 sources of Epinephrine
→ Adrenal medulla
→ Norepinephrine
Only released if there is stress
Epinephrine
1st responder to stress
Epinephrine
“Fight or Flight hormone”
Epinephrine
Potent catecholamine
Epinephrine
Epinephrine ___ (inc/dec) ___ concentration by allowing
____
increases;
glucose ;
glycogenolysis
breakdown of glycogen
into its simpler units
glycogenolysis
promoting breakdown of glycogen
into its simpler units
Epinephrine
T/F: EPI can increase in any forms of stress
T
EPI
During stress:
___ (inc/dec) cortisol = ___ (inc/dec) PNMT activity = ____(inc/dec) EPI
↑ cortisol = ↑ PNMT activity = ↑ EPI
Specimen Collection in Epinephrine should be from
from indwelling catheter (central line)
___ is NOT performed in EPI because it may
cause ___
venipuncture
false ↑
What is the major metabolite of Epinephrine
Vanillylmandelic acid (VMA)
____ of the total catecholamine are metabolized to ___
60%
VMA
Dopamine is produced by ____ of ____
decarboxylation;
3,4-dihydroxyphenylalanine (DOPA)
Produced by decarboxylation of
3,4-dihydroxyphenylalanine (DOPA)
Dopamine
Highest concentration of Dopamine is found in the regions of the
____
brain
Major intact catecholamine found in urine
Dopamine
Metabolite in Dopamine
Homovanillic acid (HVA)
What are the 2 clinical disorder associated with AM/catecholamine
Pheochromocytoma
Neuroblastoma
Pheochromocytoma is named after the ____ color of tumor after it is stained with ___
dusky
chromium salt
Overproduction of catecholamine
Pheochromocytoma
Catecholamine-producing tumor arising from
chromaffin cells (↑ catecholamine)
Pheochromocytoma
Limited degradation capacity
Pheochromocytoma
Pheochromocytoma has Limited storage for excess ____ and
____
norepinephrine
metabolites
Pheochromocytoma:
Limited storage for excess norepinephrine and
metabolites which causes ____, therefore it will go to the
___ where it will stimulate ____:
○ ___(inc/dec) ___ and ____
spillage; circulation; response
↑ cardiac output and blood pressure
Causes hypertension with nonspecific signs and
symptoms
Pheochromocytoma
Chromaffin cells are found in ____
and ____
Adrenal Medulla;
Sympathetic ganglia
Tumor in AM: ____
pheochromocytoma
Tumor in SG: ____
paraganglioma/neuroblastoma
Fatal malignant condition in children resulting to
excessive production of Norepinephrine
Neuroblastoma
Neuroblastoma LAB RESULT:
: High ___ excretion of ____ and
____, and ____
urine;
HVA
VMA
dopamine
WHAT ARE THE 4 LAB ANALYSES UNDER ADRENAL MEDULLA
- 24-hour Urine Fractionated Metanephrines &
Catecholamines - Fractionated Free Plasma Metanephrines
- Total Plasma Catecholamines & Urine
Metanephrines - Clonidine Suppression Test
Initial test AND the Best test
24-hour Urine Fractionated Metanephrines &
Catecholamines
24-hour Urine Fractionated Metanephrines &
Catecholamines
___% sensitivity
___% specificity
98%
can measure a very small
amount of Metanephrines and Catecholamines
98% sensitivity
it will not detect other
disorders
98% specificity
Fractionated Free Plasma Metanephrines
● Sensitivity: ____
● Specificity: ____
96-100%
85-89%
with poor specificity
Fractionated Free Plasma Metanephrines
Special patient preparation in Fractionated Free Plasma Metanephrines:
the patient must be in ____ for ____ and ___
supine position;
30 minutes;
during collection
Fractionated Free Plasma Metanephrines;
____: activate _____ = stimulating ____ release/metabolism = false ___ (inc/dec)
Upright posture;
sympathetic nervous system;
NE ;
↑
Most sensitive screening profile
Total Plasma Catecholamines & Urine
Metanephrines
In Total Plasma Catecholamines & Urine
Metanephrines;
_____ is suggestive of catecholamine excess
> 2000 pg/mL
Differentiate pheochromocytoma from neurogenic
hypertension
Clonidine Suppression Test
Clonidine Suppression Test Differentiates ____ from ____
pheochromocytoma;
neurogenic hypertension
Clonidine Suppression Test Uses ____ which is an _____
clonidine;
anti-hypertensive drug
Catecholamine antagonist
anti-hypertensive drug
Clonidine Suppression Test:
STEPS:
→ ____ patient from ____ for at least ____
→ Measure _____ (1st)
→ Administer ____
→ Repeat levels after ____ (2nd)
→ Stop ; antihypertensive drugs ; 12 hours
→ total plasma catecholamine
→ 0.3 mg Clonidine
→ 3 hours (2nd)
Normal Result in Clonidine Suppression Test
> 500 pg/mL fall in plasma
catecholamine
T/F: NORMAL RESULTS OF Clonidine Suppression Test:
the difference between the 1st and
2nd collection must be ___
> 500 pg/m
Normal = ____
neurogenic hypertension
Result of Clonidine Suppression Test which indicates Pheochromocytoma
<500 pg/mL fall in plasma
catecholamine
No clonidine suppression occurred
In cases of Pheochromocytoma