Adrenal medulla

Question 1

hormones secreted by adrenal medulla:

Answer 1

catecholamines:
- adrenaline (80% of secretion)
- noradrenaline (norepinephrine)
- dopamine
- is sympathetic ganglion

Question 2

roles of catecholamines:

Answer 2

• immediate response to “stress” (of any kind)
• response to the body’s needs such as: muscular exercise
• maintaining certain parameters constant such as : blood pressure, blood glucose,etc.
• Catecholamines then, serve to protect the body’s vital functions

Question 3

embryological origin of adrenal medulla:

Answer 3

neural crest

Question 4

precursor for synthesis of catecholamines ?

Answer 4

phenylalanine

Question 5

biosynthesis of catecholamines process:

Answer 5

• hydroxylation of phenylalanine by phenyl-hydroxylase = tyrosine; hydroxy of tyrosine = dopa: (here starts feedback to limit cate synthesis); decarboxylation of dopa = dopamine puis beta hydroxy = noradrenaline; puis methylation of nora = adrenaline (by phenylalanine-N-methy- transferase)

Question 6

stimulation of secretion of catecholamines:

Answer 6

The nerve pathway of the sympathetic nervous system, via:
* At the central level: the hypothalamic, bulbar and medullary centers
* At the peripheral level: the splanchnic nerves

Question 7

nerve stimulation comes in response to different stimuli (nerve pathway)

Answer 7

• Reflex, when it occurs:
  o Low blood pressure: perceived by the baroreceptors at the level of the arch of
  the aorta and the carotid sinuses
  o hypoxia or hypercapnia: perceived by carotid chemoreceptors (stimulus’s)
• Central: when it occurs: hypoglycemia, hypothermia (stimulus’s)
• Intercentrale: during pain, emotion, stress, muscular exercise (stimulus’s)

Question 8

nerve stimulation, (some hormones)

Answer 8

• Adrenocorticotropic Hormone (ACTH):
  stimulates the synthesis of dopa and norepinephrine
• Cortisol: stimulates the synthesis of adrenaline and norepinephrine

Question 9

The retrocontrol of the secretion of catecholamines :

Answer 9

direct action on: * the centers of the central nervous system
* the carotids
* the enzyme tyrosine hydroxylase (which produces dopa)
- ⚑o Hydroxylation of phenylalanine by phenylalanine hydroxylase gives tyrosine
o Tyrosine hydroxylation by tyrosine hydroxylase produces dopa
(feedback occurs at this stage to limit catecholamine synthesis ⚑

Question 10

Beta 1 receptors of catecholamines: (outnumber B2)

Answer 10

• heart: increases strength and heart rate
• adipose tissue: stimulates lipolysis

Question 11

Beta 2 receptors of catecholamines: (have an affinity for adrenaline)

Answer 11

o Kidneys: stimulates renin secretion
o Liver: stimulates glycogenolysis
o Smooth muscles of the vessels: Relaxation (of the musculature of the intestine,
bronchi, urinary tract, myometrium)

Question 12

Alpha 1 receptors: (located in vessels)

Answer 12

o vasoconstriction (at the level of the mucous membranes, skin, kidneys, viscera)
o Contraction of sphincters

Question 13

Alpha 2: (at membranes of axon terminals

Answer 13

inhibition of the release of norepinephrine

Question 14

action of catecholamines on organs:

Answer 14

Heart and vessels :
* Positive chronotropic effect
* Positive inotropic effect
* Increase venous return
* Increase peripheral vascular resistance :
o vasodilation in active territories (muscle, coronary)
o vasoconstriction in inactive territories (splanchnic, renal, cutaneous)
- consequences:  Increased cardiac output and blood pressure
 Increased myocardial oxygen consumption
3) Striated muscles :
Increases tone and delays fatigue
(the secretion of catecholamines increases with physical activity)
4) The glands :
o Inhibition of secretions from all glands (gastric, nasal, salivary, pancreatic, etc.)
o except the secretion of the sweat glands which persists
(in case of fear, the mouth becomes dry and one sweats)
5) Central nervous system :
catecholamines would increase wakefulness and alertness
(but this action remains debated)

Question 15

action on smooth muscle of organs:

Answer 15

• Intestine: decreased motility, contraction of sphincters
• Uterus: stimulation of Beta2 receptors leads to relaxation,
  stimulation of Alpha receptors leads to contraction
  (there are beta2-mimetic drugs indicated in women at risk of premature labour)
• Bronchi: action mainly on Beta2 which causes bronchodilation
  (this Beta2-mimetic property is used therapeutically for a bronchodilator effect in
  cases of asthma)
• Eye: action on Beta2 is responsible for mydriasis
• Bladder, urethra: relaxation of the bladder wall
  and contraction of the bladder and the urethral sphincter
  (beta2-mimetics also have an indication in urinary incontinence)

Question 16

Cellular metabolic actions : (mainly on beta receptors)

Answer 16

1) Carbohydrates:
o Muscle glycogenolysis
(more than hepatic, and therefore catecholamines have little effect on glycemia)
o Inhibition of insulin secretion
2) Lipids: lipolysis
3) Electrolytes: hyperkalaemia
4) Thermal regulation: Thermogenesis by
o Increased metabolism and calorigenesis
o Cutaneous vasoconstriction which reduces heat loss

Question 17

inactivation of catecholamines:

Answer 17

• uptake: Excess secreted = captured by nerve endings, in target tissues+
  stored in vesicles (protecting them from chemical catabolism)
• chemical inactivation:
  Actual catabolism, under alternating or successive action of two enzymes, depending on the tissue.
  These enzymes are located in all cells, mainly those of the liver and kidneys.
  Their action is as follows :
   Methylation: Catechol-oxy-methyl-transferase COMT: (acts in 70% of cases)
  Mainly degrades circulating catecholamines, into methoxylated derivatives:
  o adrenaline → metaepinephrine (met-A)
  o norepinephrine → normetanephrine (met-NA)
• Deamination under effect of Monoamine oxidase (MAO): (acts in 20% of cases)
  Mainly degradation of norepinephrine in nerve endings
• elimination: metabolites of the 2 enzymes (COMT and MAO), are conjugated following their
  hepatic passage, with glucuronic or sulfuric acid, to give their degradation products, which are eliminated in the urine:
• Vanyl Mandilic Acid (VMA)
• 3-Methyl-4-hydroxy-phenyl-glycol (MHPG)
  The 24-hour urine is then composed of:
  o VMA at 80% (corresponding to 2 - 4mg)
  o Methoxylated derivatives (metanephrine and normetanephrine) at 10-15%
  o Catecholamines (adrenaline + noradrenaline) 5%
  o And very little MHPG

Question 18

pathology of adrenal medulla:

Answer 18

2 tumors: Pheochromocytoma
and Neuroblastoma (there is hyperproduction of catecholamines and/or their metabolites)

Question 19

Pheochromocytoma VS Neuroblastoma:

Answer 19

• Pheochromocytoma: 90% benign + medullary; in adults entre 20-50ans; AHT 70% permanent; high secretion of catecholamines by the adrenal medulla
  and excess plasma production and accumulation of dopamine.
  of their methoxylated metabolites:
  metaepinephrine and normetanephrine
  (preferentially formed by catechol-oxy-methyl-transferase COMT)
• Neuroblastoma: malignant; in early childhood; 1/3rd adrenal; 1/3 abdominal sympathetic tract
  1/3 thorax, neck; not very specific; absence of adrenaline producing enzyme, Phenyl N methyl transferase (PNMT) + accumulation of dopamine

Question 20

biological exploration Pheochromocytoma VS neuroblastoma:

Answer 20

• Pheochromocytoma: * In first intention:
  Determination in plasma (Very good diagnostic sensitivity and specificity)
  Metaepinephrine and Normetanephrine
• Neuroblastoma: * In first intention:
  Dosage in 24h urine:
  Dopamine, Vanyl Mandilic Acid (VMA)
• Others :
  Dosage in plasma:
  Tumor marker: Neuron-specific enolase (NSE)