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2/11/2013

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The adrenal glands are situated at the upper poles of each kidney
and consist of an outer cortex surrounding a central medulla
The adrenal glands are situated at the upper poles of each kidney
and consist of an outer cortex surrounding a central medulla
10- 20 %
(Neuroectodermal tissue)
80 - 90 %
(mesodermal tissue)
Epinephrine
Norepinephrine
CATECHOLAMINES
CORTICOSTEROIDS
Mineralocorticoid
Glucocorticoid
Androgen
GLUCOCORTICOID
MINERALOCORTICOID
ANDROGENS
3 histological zones
1. Zona glomerulosa (aldosterone, mineralocorticoid)
2. Zona fasciculata (glucocorticoids, cortisol and corticosterone)
3. Zona reticularis ( androgens , DHEA, DHEA sulfate)
21 carbon atom compounds
- mineralocorticoid (aldosterone)
affects Na & K metabolism
- glucocorticoids (cortisol &
corticosterone) affect carbohydrate
and protein metabolism

19 carbon atoms
- adrenal androgenes

18 carbon atoms
- estrogen

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Zona glomerulosa
Pregnenolone
Progesterone
11-Deoxycortico
sterone
Corticosterone
Aldosterone
Angiotensin II
(2)
(3)
(4)
(5)
Cholesterol
Pregnenolone
Progesterone
11-Deoxycorticosterone
Corticosterone
17-OH
Pregnenolone
DHEA
Androstene-
dione
(2)
(1)
17-OH
Progesterone
(2)
11-Deoxy-cortisol
Cortisol
(3)
(4)
(2)
(3)
(4)
Zona fasciculata and
zona reticularis
1) 17-hydroxylase (lacking in zona glomerulosa); 2) 3 -dehydrogenase;
3) 21 -hydroxylase; 4) 11 -hydroxylase; 5) corticosterone
Methyloxidase/ aldosterone synthase
ACTH

Higher brain centers
Hormonal
Limbic system
Hypothalamus
Pituitary
CRH
Adrenal
ACTH
ACTH
Stress
Diurnal rhythm
Cortisol
-
-
negative
feedback
Mineralocorticoids
Androgens/Estrogens
The hypothalamic-pituitary-adrenal axis
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CRH-ACTH axis is activated by:
- severe trauma - hemorrhage
- burns - heavy exercise
- pyrogens - infection and fever
- hypoglycemia - chemical intoxication
- histamine - pain
- electrical shock - surgery
- anxiety - cold exposure

Low dose test
(-) cortisol;
Normal
(+) cortisol
(-) cortisol;
ACTH secreting tumor
(+) cortisol;
Adrenal cortical tumor
High dose test
Cortisol (hydrocortisone) principal glucocorticoid
accounts for about 95% of all glucocorticoid activity
90 - 95% (protein bound), 10 -15% (free form)
mainly to globulin (cortisol binding globulin or transcortin) and
albumin
halflife 60 to 90 minutes
destroyed mainly in the liver (bile/feces, 25%), mainly
excreted in the urine
Corticosterone, Cortisone (synthetic), Prednisone (synthetic),
Methylprednisone (synthetic), Dexamethasone (synthetic)


glucocorticoid
increases blood glucose level
has slight mineralocorticoid activity
helps to resist physical, mental and other
types of stresses.
essential for life

Cortisol is not stored appreciably in the
adrenocortical cells. Hence, an acute need for
increased amounts of circulating cortisol requires
rapid activation by ACTH.

In women, the adrenal glands ultimately supply 50
60% of the androgenic hormone requirements.
Carbohydrates Metabolism (Diabetogenic Effect)
stimulates gluconeogenesis from CHON (liver)
main effect
gluconeogenic enzyme activity (glucose-6-phosphatase)
decreases glucose utilization by cells (anti insulin)
inhibiting glycolytic enzymes (glucokinase, phosphofructokinase,
pyruvate kinase)
critical for the survival during fasting adrenal diabetes
and insulin secretion



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Protein Metabolism (Catabolic/Anti-anabolic)
protein catabolism and protein synthesis
facilitate conversion of protein to glucose
proteins in the body except liver and plasma
increases plasma and liver proteins
Indirectly increases gluconeogenesis


Fat Metabolism (Catabolic/Anti-anabolic)
(+) lipolysis (growth hormone and epinephrine)
- extremities
Stimulation of gluconeogenic enzyme (fru-1,6-
biphosphatase)
Inhibition of glycolytic enzymes (pyruvate
kinase, phosphofructokinase)
(+) lipogenesis at central portion of the body
(truncal obesity)
(+) ketogenesis


Permissive action

cortisol may amplify the effect of another
hormone on a process that it does not affect
directly.
potentiates and extends the action of glucagon,
epinephrine and growth hormone

Metabolic effects
- anti-insulin
- stimulate gluconeogenesis plasma glucose
- plasma amino acid levels
- lipolysis

Renal effect:
- maintain GFR (glomerular filtration rate) and RPF (renal plasma flow)

Gastric effects:
- gastric flow and acid secretion
- mucosal cell proliferation

Vascular effect:
- Cortisol catecholamine synthesis
- enhances catecholamines synthesis via its activation of the epinephrine-
forming enzyme, PNMT.

Antigrowth effects:
- growth hormone and its action on somatic growth
- cause muscle atrophy and muscle weakness
- Ca absorption from the gut
- collagen formation leads to osteoporosis and delayed wound healing

Anti-inflammatory and anti-allergic effects:
- induce the synthesis of lipocortin, an inhibitor of phospholipase A
2.

- inhibit the production of IL-2 and inhibit the proliferation of T lymphocytes.
- inhibit the release of histamine and serotonin from mast cells and platelets.

Supression of immune response:
- inhibit the production of IL-2 and T lymphocytes

Stress adaptation:
- activates the hypothalamic-hypophyseal-adrenal axis
- has some mineralocorticoid action retain Na and water
- exerts negative feedback effect at the level of CRF and ACTH secretion


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Primary Hyperadrenalism
caused by adrenal cortex adenoma, bilateral adrenal
cortex hyperplasia and administration of large
amount of glucocorticoids.
manifested by:
Buffalo hump hypertension
Moon face hypernatremia
Truncal obesity hypokalemia
Purplish striae mild alkalosis
Weakness vertebral fractures
Osteoporosis easy bruisability
Diabetes psychiatric disorders

cortisol ACTH
Secondary Hypercorticolism
pituitary adenoma
abnormal function of hypothalamus
ectopic secretion of ACTH
cortisol ACTH
due to atrophy/ destruction of the adrenal
cortex (autoimmunity), tuberculous destruction
and cancer invasion of the adrenal cortex.
characterized by:
adrenal glucocorticoid, androgen, and
mineralocorticoid
ACTH (Low cortisol levels stimulate ACTH secretion
by negative feedback.)

cortisol ACTH
Hypoglycemia
Skin hyperpigmentation
Hypotension
ECF volume shock
hyponatremia
hyperkalemia
metabolic acidosis
Pubic/axillary hair in women


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is caused by primary deficiency of ACTH.
does not exhibit hyperpigmentation
does not exhibit volume contraction,
hyperkalemia, or metabolic acidosis
Symptoms are otherwise similar to those of
Addison's disease.

cortisol ACTH
Dehydroipeandrosterone (DHEA) and
androstenedione
principal cortical androgens
responsible for the early development of male sex
organs.
converted to testosterone (potent)
musculinizing effect
also secrete estrogen (estradiol) and progesterone
develops intense musculinizing effects throughout
the body (virilism)
Growth of beard
Deeper voice
Baldness
Musculine hair distribution
Growth of clitoris
Loss of regular of menses
Regression of breast tissue
renal tubular reabsorption of sodium (DCT and
CD)
renal tubular secretion of potassium (DCT and
CD)
renal tubular secretion of hydrogen (DCT and CD)
maintenance of ECF volume (principal function)
same effect (sweat glands, salivary glands, intestinal
epithelial cells (colon)
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caused by a tumor of the zona glomerulosa cells
or hyperplasia of the adrenal cortices.
manifested by:
hypokalemia
ECFV (slight)
plasma Na
+
concentration (very slight)
Hypertension
Renin secretion
Metabolic alkalosis
muscle weakness
aldosterone level renin level


Secondary Aldosteronism
- aldosterone level renin level
negative feedback
tumor (kidney)