Physiology of the adrenal gland

DR NYEIN NYEIN WAI

ASSOCIATE PROFESSOR
Learning outcomes
The student will be able to
1. describe the synthesis of adrenocortical hormones.
2. describe the synthesis of adrenomedullary hormones
3.describe the actions of glucocorticoids and aldosterone
4. describe the actions of catecholamine
5. list the causes of hypofunction of adrenal gland
6. list the causes of hyperfunction of adrenal gland
7.describe the clinical manifestation of Cushing's syndrome
8. describe the clinical manifestation of Conn's syndrome
9. outline the principles of investigation of hypo and
hyperfunction of adrenal gland
10. outline the regulation of adrenocortical hormones
 ADRENAL GLAND
Is located above (or
attached to) the
upper pole of the
kidney.
The Adrenal Gland
Is pyramidal in
structure and
weights about four
grams.
Consists of the
adrenal cortex and
adrenal medulla
 Adrenal Cortex

• Divided into 3
zones –

Zona Glomerulosa,
Zona Fasciculata
Zona Reticularis.

• IS ESSENTIAL FOR
LIFE
 Steroid Hormone Production
• All 3 zones secrete corticosterone

• Aldosterone – only in Z glomerulosa

• Cortisol & sex hormones – Z

fasciculata & Z reticularis
Steroidogenesis
Physiological effects of Glucocorticoids
1. Effects on Intermediate Metabolism
↑protein catabolism in peripheral
tissues→↑plasma amino acid levels
stimulation of gluconeogenesis→↑ blood glucose
stimulation of glycogenesis
↓glucose uptake and utilization (anti-insulin
action) in peripheral tissues (except brain and
heart) and in liver
Mobilization of FFA from adipose tissues
lipolysis
 2. Permissive effects:

on catecholamines to produce
pressor action, bronchodilation,
lipolysis, calorigenesis

on glucagon to produce
calorigenesis, gluconeogenesis
3. Effects on renal excretion of water

 Glucocorticoids→ ↑GFR→ efficient renal

excretion of a water load.
 Adrenal insufficiency→ water retention→
water intoxication;
-if glucose infusions are given → high
fever (due to swelling of
thermoregulatory neurones) followed
by collapse & death
In Adrenal cortex insufficiency patients
who present with circulatory collapse,
glucose infusion may cause high fever
(glucose fever) followed by collapse and
death.
This is probably due to the glucose
being metabolized and water is retained
further which dilutes the plasma (hypo-
osmolar plasma) producing :
Water intoxication; and
Swelling of thermoregulatory cells in
the hypothalamus and fever develops.
 4. Haematologic effects

 on circulating blood cells

:↓Eosinophil, Basophil, Lymphocytes
(Eosinopenia, Basopenia, lymphopenia)
↑Neutrophil, Monocytes, RBCs, and
Platelets
 on lymphatic tissues
inhibit mitotic activity and proliferation
of Lymphocytes,
 5. Effects on endocrine secretion

 Negative Feedback effects on

ACTH & CRH
 Induces
PNMT(phenylethanolamine N-
methyl transferase) which promotes
conversion of NE to E
 6. Effects on N.S

Adrenal insufficiency:
mild personality changes (irritability,
apprehension (anxiety), inability to
concentrate), insomnia
 increased smell and taste sensitivity
 slow Electroencephalographic (EEG) α-
waves
 Stress

Sympathoadrenal Hypothalamohypophyseal
axis adrenocortical axis

Catecholamines Glucocorticoids
secretion secretion

? Maintaining vascular reactivity to catecholamines or

preventing stressed induced changes from becoming
excessive
 7. Resistance to stress

Noxious/potentially noxious stimuli

(stressors) →↑circulating GCs→ essential
for survival
? By maintaining vascular reactivity to
catecholamines
? By preventing stress-induced changes from
becoming excessive
life-saving in the shortrun but harmful in the
long-run
8. On GIT
Increases gastric acid and pepsin secretion
Decreases gastric mucosal cell
proliferation-thus promotes peptic ulcer
formation
Increases absorption of fat from the
intestine into the lymph
 Pharmacological effects
1. Anti-inflammatory action: inhibit inflammatory
response to tissue injury

2. Anti-allergic effect: inhibit the release of

histamine from mast cells (as GCs decrease
basophils)

3. Anti-vitamin D action (↓intestinal absorption of

Ca++ )
4. Anti-growth action: inhibit growth + ↓secretion
of GH & TSH
 Pathological effects
Cushing’s Syndrome
Manifestations of Cushing’s syndrome
1. Consequences of :
↑ protein catabolism and muscle wasting
gluconeogenic and anti-insulin actions-hyperglycemia
mineralocorticoid activity-hypertension
2. Characteristic redistribution of body fat-central obesity
3. ↑ in secretion of adrenal androgens-virilization of
women
 Face appears round Cushing’s Syndrome
(“moon-faced”) and red
– Trunk tends to become
obese from disturbances in
fat metabolism
– Limbs become wasted
from muscle atrophy
– Purple stretch marks may
appear on the abdomen,
thighs, and breasts
– Weakened bones are at
increased risk for fracture,
osteoporosis
– K+ depletion, weakness
– Hypertension
– Mental aberrations
– Precipitate diabetes
– Hirsutism (increase in
facial hair), acne –due to
increase secretion of
adrenal androgen
Feedback control of the secretion of cortisol and other GCs via
Hypothalamic-pituitary adrenal axis
 Assessment of Adrenal Cortical Function

Diagnostic
flowchart for
evaluating
Decrease plasma
patients ACTH & cortisol
suspected of
having Cushing’s
syndrome
Dexamethasone suppression test

In normal subjects: Decrease in plasma ACTH and Cortisol

In adrenal tumours: ACTH decreases but glucocorticoids

increase markedly

In etopic ACTH production: Both ACTH and glucocorticoids

increase markedly
 Effects of Mineralocorticoids
1. Retention of Na+ (water) in ECF→↑ECF
volume but no oedema due to escape
phenomenon ( release of ANP)

2. Kaliuresis → hypokalaemia

3. ↑in urine acidity → metabolic alkalosis

 Adrenocortical Hyperfunction
I. Glucocorticoid excess: Cushing’s syndrome
II. Hyperaldosteronism
Primary hyperaldosteronism (Conn’s syndrome)
Causes
- Tumour of zona glomerulosa
- Formation of ACTH-sensitive aldosterone synthase

- Absence of 11 β-OH steroid dehydrogenase ( the

enzyme that convert cortisol to cortisone ), cortisol
bind to MC receptors in renal CD to exert aldosterone-
like actions
Secondary Hyper-aldosteronism, seen in
conditions that activate RAAS

Effects of hyperaldosteronism
1. ↑ECF volume & hypertension, no oedema
due to escape phenomenon
2. Hypokalaemia → muscle weakness &
nephron damage
3. Metabolic alkalosis → hypocalcaemic tetany
 Regulation of aldosterone secretion

Aldosterone secretion is regulated by

1. RAA system (major control)

2. ACTH of anterior pituitary (larger doses

required but only transient effect seen)

3. Changes in plasma Na+ and K+ levels

 Causes of Adrenocortical
insufficiency
• Total destruction of adrenal gland: Fatal
• Causes : Infection (tuberculosis)
Metabolic (haemochromatosis)
Malignancy(cancer meastasis)
Autoimmune
Surgical removal
 Adrenocortical Insufficiency
• Symptoms & Signs

– fatigability, weakness,
anorexia, nausea,
vomiting, diarrhoea,
weight loss,
hyperpigmentation,
hypotension, women -
loss of axillary and
pubic hair
– can lead to severe
volume depletion and
shock
 Assessment of Adrenal Cortical Function

• Diagnostic
flowchart for
evaluating
patients with
suspected
adrenal
insufficiency
 Adrenal Medulla is the
sympathetic portion of the ANS
where Post-ganglionic cells have
lost their axons and become
secretory endocrine cells.
1. E. secreting cells - 90%
2. NE secreting cells - 10%
3. Dopamine secreting cells - ?
 Adrenal Medulla:
A Modified Sympathetic Ganglion

Figure 11-10: The adrenal medulla

 Synthesis of Catecholamines
Tyrosine DOPA Dopamine

Noradrenaline

PNMT
Adrenaline
 Effects of ADR & NA
• Mimick the effects of NA nervous discharge
• Metabolic effects
– Glycogenolysis (muscle & liver) - ↑ Blood glucose
level
– Mobilization of FFA (lipolysis)
– ↑ Plasma lactate
• Stimulation of metabolic rate
• ↑ Rate & force of contraction of isolated heart
• ↑ Myocardial excitability
• Vasoconstriction
• ↑ Alertness
 Effects
ACTIONS OF of Dopamine
DOPAMINE

• Renal vasodilation
• Vasodilation in mesentry
• Elsewhere – vasoconstriction
• Positive inotropic effect on heart
• Net – increase in systolic BP, no change in
diastolic BP
• Useful in treatment of traumatic &
cardiogenic shock
 Regulation of adrenal medullary secretion

• Neural control
– Emergency situations – fight or flight reaction,
through sympathetic system stimulation

• NA secretion – selectively increased by emotional stresses

with which individual is familiar

• ADR secretion – selectively increased in situations in

which individual does not know what to expect
Pheochromocytoma
E.- Secreting tumour - Hyperglycemia
NE - Secreting tumour - Hypertensive