ADRENAL MEDULLA Flashcards
• any of a class of aromatic amines that includes a number of neurotransmitters
Catecholamines
Catecholamines (4)
- DOPA
- Dopamine (D)
- Norepinephrine (NE)
- Epinephrine (E)
- derived from the sympathetic nerve endings
Norepinephrine (NE)
- principal product of adrenal medulla
- made only in the medulla
Epinephrine (E)
DOPA
L-3,4-dihydroxyphenylalanine
L-3,4-dihydroxyphenylalanine
DOPA
is a precursor molecule in the biosynthesis of catecholamines, including dopamine, norepinephrine, and epinephrine.
can cross the blood-brain barrier and is converted to dopamine, aiding in brain function.
DOPA
DOPA
Processes:
1. Formation: L-Tyrosine is hydroxylated by ________in the cytosol to form DOPA. This is the rate-limiting step in catecholamine biosynthesis.
2. Conversion to Dopamine: DOPA is decarboxylated by \_\_\_\_\_\_in tissues like the adrenal medulla and neurons, producing dopamine.
tyrosine hydroxylase (TH)
aromatic amino acid decarboxylase (AADC)
L-Tyrosine Conversion to L-Dopa
Enzyme:________
Location:______ of adrenal medullary cells and other locations like sympathetic nerve terminals.
Function: Adds a hydroxyl group to L-tyrosine, forming L-Dopa (rate-limiting step in catecholamine synthesis).
Tyrosine hydroxylase (TH)
Cytosol
L-Dopa Conversion to Dopamine
Enzyme:_______
Location: Present in various tissues, including the adrenal medulla.
Function: Removes a carboxyl group from L-Dopa to produce_____
Aromatic amino acid decarboxylase (AADC)
dopamine (DA).
Dopamine Transport into Chromaffin Granules:
Transporter:_________
Mechanism: Acts as a dopamine-H+ exchanger, pumping dopamine into chromaffin granules (dense-core vesicles).
VMAT1 (Vesicular Monoamine Transporter-1)
Dopamine Conversion to Norepinephrine (NE):
Enzyme:_________
Location:__________
Function: Converts dopamine to norepinephrine (NE) by adding a hydroxyl group.
Dopamine beta-hydroxylase (DBH)
Inside chromaffin granules
Norepinephrine Conversion to Epinephrine (E):
Enzyme:_________
Location:__________ of adrenal medulla (unique to adrenal medulla).
Function: Transfers a methyl group from S-adenosylmethionine (SAM) to
norepinephrine to produce epinephrine (E).
Phenylethanolamine-N-methyl-transferase (PNMT)
Cytosol
Transport of Epinephrine Back into Chromaffin Granules:
Transporter:_____
________is reabsorbed into chromattin granules for storage.
VMAT1
Epinephrine
Storage
Catecholamines bind with______ and _____ to proteins called______, which help in storage.
• This binding makes the catecholamines osmotically inactive, preventing them from diffusing freely and maintaining a controlled storage state.
• Among the chromogranins,______ is the most abundant in humans and plays a major role in the regulation and packaging of catecholamines within these granules.
calcium (Ca2+) and ATP
chromogranins
chromogranin B
- Hormone Release:
• Mechanism:
- _______ trigger exocytosis of chromaffin granules.
- Both epinephrine (E) and norepinephrine (NE) are released into the bloodstream.
Calcium ions (Ca2+)
Physiologic Actions
•________
- coupled with G Protein (termed as GPCR)
• Alpha
• Beta
Adrenergic Receptors
Adrenergic Receptors Overview
Adrenergic receptors are a type of GPCR that, upon activation by catecholamines, initiate a cascade of intracellular signaling events.
These events typically involve the activation of intracellular second messengers, such as cyclic AMP (cAMP) or calcium (Ca²⁺), depending on the receptor subtype.
G-Protein Coupled Receptors (GPCRs)
Receptor???
Effectively Binds
Epinephrine, Norepinephrine
Effect of Ligand Binding
Increased free calcium
Alpha1
Recotor???
Epinephrine, Norepinephrine
Decreased cyclic AMP
Alpha2
Receptor???
Epinephrine, Norepinephrine
Increased cyclic AMP
Beta1
Receptor???
Epinephrine
Increased cyclic AMP
Beta2
Adrenergic Receptors
- ___is a post-synaptic receptor (three subtypes: 1A, 1B and 1D);
-___ is both post- and pre-synaptic receptor (three subtypes: 2A, 2B and 2C)
Alpha 1
Alpha 2
Andrenergic Receptors
- _____ located mainly in the heart and cortex;
- _____ predominates in the lung and cerebellum;
- _____ in the adipose tissue
• significance in obesity
Beta 1
Beta 2
Beta 3
- a response when faced with severe external threat
- centrally driven release of____, as well as activation of other aspects of sympathetic division of ANS
Fight-or-flight response
adrenaline
- increased heart rate and contractility
- mobilization of fuel stores (muscle and fat)
- piloerection
- pupillary dilation
- increased sphincter tone of bowel and bladder
Fight-or-flight response
Short-term stress response
- Increased heart rate
- Increased blood pressure
- Liver converts glycogen to glucose and releases glucose to blood
- Dilation of bronchioles
- Changes in blood flow patterns leading to increased alertness, decreased digestive system activity, and reduced urine output
- Increased metabolic rate
- Increased heart rate
- Increased blood pressure
- Liver converts glycogen to glucose and releases glucose to blood
- Dilation of bronchioles
- Changes in blood flow patterns leading to increased alertness, decreased digestive system activity, and reduced urine output
- Increased metabolic rate
Short term stress response
- Retention of sodium and water by kidneys
- Increased blood volume and blood pressure
- Proteins and fats converted to glucose or broken down for energy
- Increased blood sugar
- Suppression of immune
system
Long-term stress response
Long term stress response
- Retention of sodium and water by kidneys
- Increased blood volume and blood pressure
- Proteins and fats converted to glucose or broken down for energy
- Increased blood sugar
- Suppression of immune
system
Adrenal Medulla
Specific Physiologic Actions
•
- this is predominantly an effect of epinephrine acting through beta receptors
increased rate and force of contraction of the heart muscle
Adrenal Medulla
Specific Physiologic Actions
•
- norepinephrine, in particular, causes widespread vasoconstriction, resulting in increased resistance and hence arterial blood pressure
Constriction of blood vessels
Adrenal Medulla
Specific Physiologic Actions
•
- assists in pulmonary ventilation
Dilation of bronchioles
Adrenal Medulla
Specific Physiologic Actions
•
- this provides fatty acids for energy production in many tissues and aids in conservation of dwindling reserves of blood glucose
Stimulation of lipolysis in fat cells
Adrenal Medulla
Specific Physiologic Actions
•
oxygen consumption and heat production increase throughout the body in response to epinephrine
- medullary hormones also promote breakdown of glycogen in skeletal muscle to provide glucose for energy production
Increased metabolic rate
Adrenal Medulla
Specific Physiologic Actions
•
- particularly important in situations where you are surrounded by velociraptors under conditions of low ambient light
Dilation of the pupils
Adrenal Medulla
Specific Physiologic Actions
•
- an example is inhibition of gastrointestinal secretion and motor activity
Inhibition of certain “non-essential” processes
Adrenal Medulla
Specific Physiologic Actions
• Common stimuli
(4)
- Exercise
- Hypoglycemia
- Hemorrhage
- Emotional distress
Catecholamines
Degradation and Elimination
• METABOLITES (3)
• Excreted via the_____
- Free Cathecolamines
- Vanillylmandelic acid
- Metanephrines
kidneys
Catecholamines
Degradation and Elimination
• EXCRETION
- Free Cathecolamines
- Conjugated NE
- Metanephrines
- Vanillylmandelic acid
5%
8%
20%
30%
Diseases
• Pheochromocytoma
• Neuroblastoma
Diseases
- Rare cathecolamine-producing tumors
Pheochromocytoma
• Triad
- Diaphoresis
- Tachycardia
- Headache
Pheochromocytoma
Pheochromocytoma
• Triad
- Diaphoresis
- Tachycardia
- Headache
• Pheochromocytoma
24-Hour Urine
•_______ is measured to verify the adequacy of the collection
•_______- preservative
Creatinine
25 mL of 6N HCI
Pheochromocytoma
Plasma
•______ specimen colloection
• Patient in a_____ position in a quiet environment, and a heparin lock is inserted IV
• After______ minutes, collect blood in a_____
• Whole blood be kept in ice water until centrifuged
• Plasma should be separated within____ hours of phlebotomy
• Sample should be frozen immediately
Overnight fast
reclining
20-30mins; pre-chilled EDTA
2 hrs
A rare tumor that produces excessive amounts of catecholamines (epinephrine, norepinephrine).
These tumors arise from chromaffin cells of the adrenal medulla or extra-adrenal sympathetic tissue.
Pheochromocytoma
excessive sweating
Diaphoresis
Pheochromocytoma
Urine Tests
- 24-Hour Urine Collection:
• Measures levels of catecholamines and their metabolites:
(3)
• ______ is measured to verify the adequacy of the collection.
• Preservative: 25 mL of _____is added to the collection container.
• Free norepinephrine (NE).
• Vanillylmandelic acid (VMA).
• Homovanillic acid (HVA).
Creatinine
6N HCl
Pheochromocytoma
Plasma Tests
1. Pre-Procedure Preparation:
• ______fasting.
• The patient should remain in a_____ position in a quiet environment.
• A heparin lock is inserted intravenously.
- Sample Collection:
• Blood is collected after_____ using a______ tube.
• The sample must be kept in ice water until centrifuged. - Sample Handling:
• Plasma must be separated within _____of phlebotomy.
• The sample should be frozen immediately for preservation.
Overnight; reclining
20-30 minutes; pre-chilled EDTA
2 hours
Imaging Studies:
Highly sensitive for detecting catecholamines and their metabolites.
Identifies tumor size and location.
Provides detailed imaging of adrenal and extra-adrenal sites.
HPLC with Tandem Mass Spectrometry
CT (Computed Tomography)
MRI (Magnetic Resonance Imaging)
Pheochromocytma
• Purpose: Differentiates catecholamine release from pheochromocytoma versus nervous system activity.
• Mechanism: ______, an alpha-adrenergic agonist, suppresses nervous system catecholamine release but does not affect tumor secretion.
Clonidine Suppression Test
Clonidine Suppression Test:
Definition:
A tumor derived from neural crest cells, typically affecting children younger than 3 years.
_______ commonly arise in the adrenal medulla but can occur in other sympathetic nervous system sites.
Neuroblastoma
• Key Features:
• High urinary levels of:
• Homovanillic acid (HVA)
• Vanillylmandelic acid (VMA)
Neuroblastoma
