Basic Anatomy of Adrenal Glands

Hormones of the Adrenal Cortex

All adrenocortical hormones are steroids (fat soluble). Three
groups:
Glucocorticoids (cortisol in humans)
Mineralocorticoids (aldosterone)
Adrenal sex hormones (most important is dehydroepiandrostenone
= DHEA)

Cortex has three layers.

Zona glomerulosa
Zona fasciculate
Zona reticularis
 Mineralocorticoid (aldosterone)
Promotes Na+ reabsorption and K+ secretion in distal convoluted
tubule. This is how total body Na+ is regulated by the kidney.

Since Na+ is the major cation in ECF, controlling Na+ content controls
plasma volume and arterial pressure.

In absence of aldosterone, Na+ depletion lowers plasma volume and

arterial pressure to fatal levels in 7 to 10 days. Added dietary salt
can prevent this in acute cases. Elevated plasma K+ can disrupt
cardiac rhythm. Long term maintenance is by administration of
mineralocorticoids.
 Control of aldosterone secretion
Aldosterone secretion is stimulated by decreased plasma Na+,
increased plasma K+, and decreased arterial pressure.

ACTH has a very small influence on aldosterone secretion.

 Glucocorticoids (mostly cortisol)
Metabolic effects:
1. Stimulates protein degradation -> muscle wasting and
increased levels of plasma amino acids
2. Stimulates conversion of amino acids to glucose in the liver
3. Inhibits glucose uptake from plasma, except in brain
4. Increases plasma glucose levels
5. Promotes lipid breakdown, increasing plasma lipid levels
6. This conserves glucose for the brain, other tissues burn fat

Permissive effect: Sympathetic responses require presence of some

cortisol.

Anti-inflammatory and immunosuppressive effects: Well known,

but unimportant physiologically. Pharmacologically important,
usually cortisone or hydrocortisone rather than cortisol.
 Control of Cortisol Secretion
Major stimulus to secretion is ACTH. ACTH (Adrenocorticotrpic
hormone) secretion is inhibited by cortisol (negative feedback loop),
as is CRH (corticotropic RH) secretion.

Stress increases cortisol secretion. Probably by neural stimulation of

CRH output from hypothalamus via brain pathways.

Cortisol secretion varies during each 24 hour cycle. Highest in

morning. Also a result of brain influence on endocrine system.
 Hypersecretion of Cortisol (Cushing’s syndrome)
Result from cortisol secreting tumor, excess ACTH and/or excess CRH

Causes muscle wasting and elevated plasma glucose levels.

Increased subcutaneous fat deposition, especially in the face.

 Adrenal Cortex Atrophy
Addison’s disease = atrophy of the adrenal cortex. Results in
hyposecretion of cortisol and aldosterone.

Hyposecretion of cortisol reduces plasma glucose and amino acid

levels, but we can compensate.

Hyposecretion of aldosterone causes loss of Na+, can be fatal in

fairly short time. Can be treated with oral NaCl, though.
 Adrenal Sex Hormones
Dehydroepiandrostenone (DHEA) is a male sex hormone. Effects are
similar to those of testosterone, but has much less potency.

The only masculinizing hormone in women. Hypersecretion

masculinizes: male body hair distribution, facial hair (hirsutism),
increased muscle definition, deepening of voice, etc. Also causes
reduction in breast size, menstrual abnormalities.

Irrelevant in men. Even men with low testosterone levels have so

much testosterone in their plasma that DHEA levels are trivial.

Pre-pubertal boys with elevated DHEA levels develop adult male

secondary sex characteristics, called precocious puberty. They look
like they’ve gone through puberty, but they don’t produce sperm.
Testosterone levels in the testes aren’t nearly high enough to support
sperm production.
 Adrenal Medulla
Refresher on sympathetics: Preganglionic neurons in CNS synapse
with postganglionic neurons in ganglia, releasing ACh from axon
terminals. Postganglionic neurons project axons to target cells,
releasing norepinephrine from axon terminals.

Neurons from CNS project axons to adrenal medulla, releasing ACh

from axon terminals. Adrenal medullary cells release epinephrine
and norepinephrine (4:1 ratio) into circulation. Epinephrine and
norepinephrine have similar, but not identical effects. Also known
as adrenalin and noradrenalin, for historical reasons.

Thus, adrenal medulla is essentially part of the sympathetic branch

of the autonomic nervous system.
It’s been known since the 19th century that cells of the adrenal
medulla stain vividly with histological stains. For that reason, they
are called chromaffin cells. The vivid staining is in hormone-
containing granules, known as chromaffin granules.

When you are startled, you have immediate responses (increased

heart rate and stroke volume, for example), which gradually come
back to normal within a minute or so. The immediate response is
neural (sympathetic), the prolonged response is from adrenal
medullary hormones.
 Adrenal Medullary Disorders
1. Deficiency: No known deficiency disorders. Maybe they exist
but are compensated by sympathetic nervous system.

2. Excess: There are adrenal medullary tumors that secrete large

amounts of epinephrine and norepinephrine. These are known
as pheochromocytomas. Symptoms are what you might expect
of sympathetic hyperactivity; irritability, elevated plasma
glucose levels, hypertension, etc.
 Endocrine Control of Circulating Fuels

We absorb fatty acids and glycerol, amino acids, and sugars from
the gut; store them as fats, proteins and glycogen.

Most of stored protein is muscle; increased by increasing muscle

mass, only mobilized under starvation conditions. Sugars are
stored in muscle and liver as glycogen, amount we can store is
very limited. Lipid is stored as fat, virtually unlimited amount.

When we have more sugar and/or amino acid than can be stored,
they’re converted into and stored as fat.
Brain can only use glucose as fuel. Probably for this reason, plasma
glucose levels are closely regulated. Normal level is about
1 mg/ml = 100 mg/100 ml = 100 mg/dL = 100 mg% = 3 mM

Regulation is by having other tissues burn fatty acids when glycogen

stores are depleted, and converting other compounds to glucose
(gluconeogenesis).

We eat periodically, rather than continuously. Therefore, there are

two metabolic states: (1) Fed or absorptive state, when nutrients
are being absorbed from the gut. (2) Fasting or postabsorptive
state, when not much is being absorbed from the gut.

During fed state, glucose is used as fuel, and is converted into

glycogen and fat for storage. During fasting state, glycogen and fat
are converted to glucose, and most cells use fats as fuel. This
conserves glucose for the brain. The state we are in is under
endocrine control.
Epinephrine, norepinephrine, cortisol and GH affect plasma glucose
levels. But the major influences come from two polypeptide
hormones secreted by the endocrine pancreas (islets of
Langerhans).
1. Insulin, produced by beta cells
2. Glucagon, produced by alpha cells.

Insulin’s most important effects:

1. Promotes glucose uptake by liver and muscle, decreasing
plasma glucose levels.
2. Promotes increased glycogen in liver and muscle by stimulating
glycogen synthesis and inhibiting glycogen breakdown.
3. Promotes uptake of fatty acids and amino acids and their
conversion into fat and protein.
 Significance of Splanchnic Circulation
Venous drainage of pancreas goes straight to liver. Thus, insulin
reaches liver before dilution in circulation.

Venous drainage of small intestine goes straight to liver. Thus,

absorbed nutrients reach liver before dilution in circulation.

Liver is one of the two major sites of insulin action.

 Control of Insulin Secretion
Plasma glucose concentration. As plasma glucose levels increase,
insulin secretion increases.

Neural control. Sympathetic stimulation inhibits insulin release

(that’s why sympathetic stimulation increases plasma glucose
levels), parasympathetic stimulation promotes insulin release
(parasympathetic output increases while meals are being
digested).
 Diabetes Mellitus
Diabetes = high volume of urine
Mellitus = honey-like

Urine of victim is sometimes very sweet, attracts flies and dogs.

This has been known for at least 500 years. The sweetness comes
from a high glucose content (normal urine has none).

Plasma glucose levels can exceed transport maximum in kidneys,

increasing volume osmotically. Plasma glucose is elevated because
insulin’s effects aren’t happening.

This is the most common of all endocrine disorders, although it’s

actually two very different disorders with the same name and
symptoms.
 Types of Diabetes Mellitus
Type I: Insufficient insulin secretion by beta cells
Type II: Reduced sensitivity of cells to insulin

Effects are the same either way – insulin’s effects are blunted or
absent. Sometimes described as starvation in the midst of plenty,
because cells are bathed in a nutrient-rich environment but can’t
transport the nutrients into cells where they can be used.
 What happens in diabetes mellitus?
Glucose output from liver increases, glucose uptake into liver,
muscle and other cells decreases. Therefore, plasma glucose levels
rise (hyperglycemia)

Protein is broken down and resulting amino acids are converted

into glucose. This leads to muscle wasting.

When plasma glucose levels get above 3 mg/ml, glucose enters

urine (glucosuria) and urine volume expands osmotically.
 Effects of high rate of loss of water
Person drinks lots of water (thirst is a compensatory mechanism when
plasma volume falls). Despite this, dehydration occurs; the water
intake doesn’t quite compensate for the water loss.

Dehydration reduces arterial pressure, reducing tissue perfusion. This

can cause renal failure, poor wound healing, neuropathies.

Reduced intracellular glucose levels cause hunger and increased food

intake. Despite this, cells continue to starve, and fats are used for
energy by most cells.

Fat metabolism results in some ketones as end products, giving a

characteristic sweet odor to breath (acetone is a commonly used
ketone). It also reduces plasma pH because some end products are
organic acids, less volatile than CO2. Acidosis can progress to cause
coma or death.
 Treatment of Diabetes Mellitus
Type I – Treated with insulin

Type II – Treated with drugs that stimulate insulin secretion. Since

person can produce insulin, it’s often possible to overcome the
reduced sensitivity to it this way. Mild cases can often be
controlled by diet and exercise.

Exercise is valuable for any diabetic, because glucose uptake by

muscle rises during exercise independently of insulin.

If a Type I diabetic overdoses on insulin, hypoglycemia can result.

Depriving the brain of a glucose supply can cause loss of
consciousness.
 Glucagon
If you understand insulin, glucagon is easy. Everything is simply
opposite to what’s true for insulin.

Glucagon increases gluconeogenesis and decreases glycogen

synthesis in liver, thus increasing plasma glucose levels.

Glucagon promotes fat breakdown, inhibits protein synthesis and

promotes protein breakdown.

Glucagon secretion is also controlled by plasma glucose levels, but

increased levels of glucose reduce glucagon secretion.