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KELENJAR ADRENAL
2. Adrenal Medulla-
20%
CORTICOSTERIODS – group of hormones secreted by the
adrenal cortex. These are synthesized from the steroid
Cholesterol. The following are the ADRENOCORTICAL
HORMONES:
3. Androgenic hormones
Deoxycortico- 17-OH-
progesterone
sterone
Dehydroepi-
11-deoxycortisol androsterone
Corticosterone
cortisol androstenedione
aldosterone
21 CH3
18 =O
Lipoprotein 12 17
11 16
Acetate 13
1 19
2 15
9
CH3 10 8 14
5 pathway CH3
=O HO 3 5 7
HO Cholesterol 4 6 =O
OH Pregnenolone
5 pathway
O
HO O Progesterone CH2OH
17-OH-pregnenolone
=O
O
OH Dehyroepiandrosterone
17-OH-progesterone
(DHEA)
OH O
Androstanediol Deoxycorticosterone (DOC)
O 11-deoxycortisol
-androstenedione
4
Corticosterone
HO H HO O O O
Dihydrotestosterone Estradiol Cortisol Aldosterone Progesterone
Pathways of syntheis of the major classes of steroid hormones, Cholesterol is devided from acetate by sybthesis or from
lipoprotein partcles. The numbering of the steroid molecule is shown for pregnenolone. The major pathways thought to be used
are shown.
Relative anti- Relative Na Duration of Appox equiv
compound inflam effect retain potency actions dose (mg)
Cortisol (HC) 1 1 S 20
Prednisone 0 0 - -
Prednisolone 4 0.8 I 5
4 - I 5
-m-prednisolone
5 0.5 I 4
Fluorocortisone
10 125 S -
11-desoxycortisol
0 0 - -
Cortisone 0.8
0.8 S 25
Corticosterone 0.35 15 S -
Triamcinolone 5 0 I 4
Betamethasone 25 0 L 0.75
dexamethasone 25 0 L 0.75
corticotrops ACTH
of adenohypophysis
cortisol adrenal
cortex
Hormone
Receptor
Extracellular side
Cell membrane
cAMP
Inactive R
Protein kinase A cAMP
Stimulates R
C R
Protein kinase
C R C Active
C Protein kinase A
Androgenic hormones
• DHEA – dehydroepiandrosteron
• androstenedion
• testosteron
– testosterone is a precursor of estradiol
• effects:
– anabolic
– development of the secondary sexual signs
– distribution of hair
– voice
– sexual behavior - libido
Disorders of adrenal cortex
A) Hypo function of adrenal cortex - ''ADDISION' DISEASE''
• hypotension, shock
withdrawl of GCC
sepsis
bleeding
Chronic :
- GCC & mineralocorticoid substitution
- Hydrocortison 20-25 mg/day or
Prednison/prednisolon in equivalent dose
Cushing
Cushing disease
disease :: primary
primary hypercortisolism
hypercortisolism
(from
(from pituitary)
pituitary)
Etiology :
-- Exogen
Exogen :: administration
administration of of supraphysiologic
supraphysiologic doses
doses of
of CS
CS
in
in long
long term
term
-- Endogen
Endogen :: -- pituitary
pituitary tumor
tumor (( 60-70%)
60-70%)
-- adrenal
adrenal tumor
tumor (20%)
(20%)
-- nonendocrine
nonendocrine tumors
tumors ACTH-like
ACTH-like substance
substance ::
>> Oat cell Ca (lung tumor)
>> Carcinoid bronchial
bronchial adenoma
adenoma
>> Prostat / Ovarium Ca
Ca
>> Pancreas Ca
Cushing Syndrome
Cushing’s disease
Diagnosis :
Clinical app : habitus, striae, osteoporosis, hypertension
Normal
Normal :: urine
urine 17-OCHS
17-OCHS
Cushing’s
Cushing’s dis:
dis: fail
fail to
to suppress
suppress
b) Definitive test
1.
1. Cortisol
Cortisol &
& ACTH
ACTH level
level without
without dexamethasone
dexamethasone adm
adm
2.
2. Metyrapone
Metyrapone test
test
Diagnosis :
Radiologic diagnosis :
1. X- ray : sella turcica
2. Adrenal angiography & venography :
uni/bilateral ?
3. Scanning
Treatment :
1. Surgery
2. Pituitary irradiation
3. Drugs: metyrapone ( inhibits 11-β hydroxylase )
- pre-operative
- inoperable adrenal Ca
- ectopic tumor with unknown sites or has
already metastated
Cushing’s
Syndrome
“moon face”
striae
ADRENAL MEDULLA
AND
CATECHOLAMINES
Adrenal medulla
Histology :
chromafin cells, contain granules (catecholamine)
Function :
tyrosine CATECHOLAMINE
- adrenalin
- noradrenalin
* Paraganglia cells
* CNS
* End of otonomic nerves
tyrosine
tyrosine
DOPA
DOPA (dihydroxyphenilalanine)
(dihydroxyphenilalanine)
dopamine
dopamine
PEMT
PEMT
norepinephrine
norepinephrine epinephrine
epinephrine
COMT
COMT MAO
MAO MAO COMT
COMT
MAO
normetanephrine
normetanephrine dihydroxy
dihydroxy mandelic
mandelic acid
acid metanephrine
metanephrine
COMT
COMT
MAO
MAO MAO
MAO
vanilly
vanilly mandelic
mandelic acid
acid
urine
MAO
MAO :: Mono
Mono AmineOxidase
AmineOxidase
COMT
COMT :: catechol-O-methyl-transferase
catechol-O-methyl-transferase
PEMT
PEMT :: phenyl
phenyl ethanol
ethanol amine-N-methyl
amine-N-methyl transferase
transferase
Effects :
vasodilatation
bronchodilatation
β-receptor cardiac : inotrophic &
chronotrophic effect
adrenalin
gastric motility
Autonomic Nervous System (ANS)
• Involuntary or visceral nervous system
• Regulates the activity of:
– Cardiac Muscle (Heart)
– Smooth Muscle ( In Hollow Organs)
• Blood Vessels
• Digestive System
• Bronchioles
• Sphincters
– Glands
• Adrenal
• Digestive glands
ANS Divisions
o Sympathetic: o Parasympathetic:
o “Fight or Flight” o “Rest & Digest”
o Activated during o Reduces energy use
emergencies, exercise o Promotes:
or vigorous physical digestion of food
activity
storage of energy
o Revs up body to
respond to situations elimination of
that upset homeostasis wastes
homeostasis
Mosby items and derived items © 2006 by Mosby, Inc.
Somatic versus Autonomic Pathways
15-70
Preganglionic Pathways
15-71
Efferent Pathways
15-72
Adrenal Medulla Glands
• Medulla (inner core)
– a modified sympathetic ganglion
• stimulated by preganglionic sympathetic neurons
– secretes neurotransmitters (hormones) into blood
• catecholamines (80% epinephrine and 20% norepinephrine)
• Sympathoadrenal system is the closely related
functioning adrenal medulla and symphathetic
nervous system
15-73
Ganglia and Abdominal Aortic Plexus
15-74
Parasympathetic - Origin
• Craniosacral
• Nerve fibers emerge from brain & sacrum
Parasympathetic Nervous
System
• Pathways of preganglionic fibers
– cranial nerves III, VII, IX and X
– arising from sacral spinal cord
• pelvic splanchnic nerves and inferior
hypogastric plexus
• Terminal ganglia in/near target organs
– long preganglionic, short postganglionic
fibers
15-76
Efferent Pathways
15-77
Parasympathetic Cranial
Nerves
• Oculomotor nerve (III)
– narrows pupil and focuses lens
• Facial nerve (VII)
– tear, nasal and salivary glands
• Glossopharyngeal (IX)
– parotid salivary gland
• Vagus nerve (X)
– viscera as far as proximal half
of colon
– Cardiac, pulmonary, and
esophageal plexus
15-78
Parasympathetic
Innervation of Visceral
Targets
• Ganglia close to or on target organs
• Preganglionic neurons - long
• Post ganglionic neurons - short
Parasympathetic
Neurotransmitters
• Preganglionic neurons release
acetylcholine = Cholinergic
Parasympathetic
Neurotransmitters
• Postganglionic neurons release
acetylcholine = Cholinergic
Cholinergic Receptors
• Found on skeletal muscle cells
regulated by motor neurons.
Motor Neuron
Cholinergic Receptors
• Found on dendrites & cell bodies of
postganglionic neurons of both
sympathetic and parasympathetic
divisions of ANS.
Spinal
Cord
Mosby items and derived items © 2006 by Mosby, Inc.
Sympathetic
Neurotransmitters
• Preganglionic neurons -
– Cholinergic = ( release acetylcholine )
Sympathetic Neurotransmitters
• Postganglionic neurons:
– release norepinepherine at target organs
– ie. Adrenergic
• Adrenal medulla:
– releases epinepherine & norepinepherine into
blood
– ie. Adrenergic
DOPA
DOPA (dihydroxyphenilalanine)
(dihydroxyphenilalanine)
dopamine
dopamine
PEMT
PEMT
norepinephrine
norepinephrine epinephrine
epinephrine
COMT
COMT MAO
MAO MAO COMT
COMT
MAO
normetanephrine dihydroxy
dihydroxy mandelic
mandelic acid
acid metanephrine
metanephrine
COMT
COMT
MAO
MAO MAO
MAO
vanilly
vanilly mandelic
mandelic acid
acid
urine
urine
MAO
MAO :: Mono
Mono AmineOxidase
AmineOxidase
COMT
COMT :: catechol-O-methyl-transferase
catechol-O-methyl-transferase
PEMT
PEMT :: phenyl
phenyl ethanol
ethanol amine-N-methyl
amine-N-methyl transferase
transferase
Phaeochromocytoma
1% of hypertensive pts
curable
tumors : adrenal medulla
paraganglia along aorta abdominal
(zuckerkandl)
vesica
vesica urinaria,
urinaria, mediatinum
mediatinum
Clinical manifestations :
Depend on :
• type of catecholamine which is predominant
(adrenalin or noradrenalin)
Noradrenalin
Noradrenalin ::
Adrenalin
Adrenalin ::
-- Hypertension
Hypertension -- Palpitation
Palpitation
-- Headache
Headache -- Chest
Chest pain
pain
-- Sweating
Sweating -- Tremor
Tremor
-- Pallor
Pallor -- Flushing
Flushing
-- Nausea
Nausea
• secretion : continous or paroxysmal
Paroxysmal
Paroxysmal :: Precipitating
Precipitating factors
factors ::
episodic
episodic -- exercise
exercise
-- stress
stress
(mnts
(mnts –– hours)
hours)
-- eating
eating
<< 11 hour
hour -- abdominal
abdominal palpation
palpation
Diagnosis :
- Definitive : plasma catecholamine
- 24-hours urine VMA