LECTURE 10 - adrenal medulla

Question 1

What is the adrenal medulla?

Answer 1

• Part of ANS
• Specialised ganglia supplied by sympathetic preganglionic neurones (Ach as transmitter)
• Synthesises catecholamines
• Main site for adrenaline synthesis as Phenylethanolamine-N-methyl transferase present (PNMT) – converts noradrenaline to adrenaline
• Not essential for life

Question 2

What are chromatin cells?

Answer 2

• React to NS
• Pre-packaged hormones ready to be secreted (mostly adrenaline)
• Come from migration and differentiation of primitive neutral crest??

Question 3

Describe the synthesis of catecholamines?

Answer 3

1. Tyrosine –> L-DOPA - tyrosine hydroxylase catalyses this rate-limiting step
2. L-DOPA –> dopamine - DOPA decarboxylase acts on any aromatic acid
3. Dopamine –> noradrenaline - dopmine beta-hydroxylase, occurs in synaptic vesicles
4. Noradrenaline –> adrenaline - done by PNMT

Question 4

How do you regulate adrenaline production?

Answer 4

• up regulate rate limiting step

- up regulate PNMT action

Question 5

How are catecholamines stored and regulated?

Answer 5

• Transported into synaptic vesicles using specialised transporter (vesicular monoamine transporter)
• Vesicles protect hormone from degradation and ensure control can be maintained over how much is released
• Tyrosine hydroxylase is inhibited by concentration of vesicles (kind of -ve feedback but not fully)
• High level (rate) of stimulation from nerves stimulates tyrosine hydroxylase

Question 6

How is the release of catecholamines regulated?

Answer 6

• signals from hypothalamus activate SNS –> adrenaline secretion
• some regulation by ACTH/ cortisol (not in -ve feedback system)
• looking at blood supply of medulla, comes from outside in so has to go through cortex, if cortex produced lots of cortisol, highest conc. in blood of cortisol is going to be in the point of entry vessel (this happens in stressful situations)
• PNMT expression increases with cortisol production
  HOWEVER dropping cortisol levels does not drop adrenaline levels

Question 7

How is catecholamine action terminated?

Answer 7

• taken into nerve terminals (recycled and metabolised)

- metabolic inactivation in liver/ kidneys

Question 8

What is metabolic degradation?

Answer 8

Adrenaline --> metadrenaline
(by COMT)
Metadrenaline --> VMA 
(by MAO)
excretion by kidney

Question 9

What is the difference in receptor sensitivity for adrenaline and noradrenaline?

Answer 9

Alpha receptors: A< NA
Beta receptors: A» NA

therefore adrenal medulla is the primary activator of beta receptors

Question 10

What are the systemic effects of adrenaline?

Answer 10

CVS: increased heart rate and force of contraction, vasodilation
Respiratory system: bronchodilation
CNS: increased alertness/arousal, anxiety and muscle tremor
Metabolism
- muscle: glycogen breakdown
- hepatic: increased glycogenolysis/ gluconeogenesis
- adipose tissue: mobilisations of free fatty acids
ALL –> increased blood glucose

Question 11

Why do we need SNS innervation and adrenaline from the medulla?

Answer 11

• longer lasting effects
• widespread effect, even to non-innervated tissues, blood goes to whole body where SNS cannot reach
• different effect to normal sympathetic activation

Question 12

What is phaeochromocytoma?

Answer 12

• excess of catecholamines
• caused by tumour of chromatin cells or by dramatic episodes e.g. sudden stressor
  (hard to diagnose as only seen as XS of adrenaline)

Symptoms:

• episodes of very high BP
• sudden, severe headache
• palpitations, chest pain
• pallor of skin, sweating
• anxiousness

Treatment:

• surgery
• anti-hypertensive drugs

Question 13

What can arise from hypo function of adrenal medulla

Answer 13

• e.g. malignant destruction
• no clinical problems
• sympathetic activity is sufficient