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• Difintion :
• The pituitary is an endocrine
(hormone-producing) gland that sits
just beneath the base of the brain,
behind the bridge of the nose.
• It is very small – only about the size
of a pea , and weighing 0.5 grams .
• It is very important as it takes messages
from the brain (via a gland called the
hypothalamus) and uses these messages
to produce hormones that affect many
parts of the body, including stimulating
all the other hormone-producing glands
to produce their own hormones. For this
reason it is often referred to as the
‘master gland’.
• It is composed of three lobes:
• anterior, intermediate, and posterior.
Hormones secreted
• The anterior pituitary
• synthesizes and secretes the following important
endocrine hormones. All releasing hormones (-
RH) referred to, can also be referred to
as releasing factors (-RF ) .
• 1-Somatotrophins:
• Human growth hormone (HGH), also referred to as
'growth hormone' (GH) , and also as somatotropin,
is released under the influence of
hypothalamic growth hormone-releasing
hormone(GHRH), and is inhibited by
hypothalamic somatostatin
• 2- Thyrotrophins:
• Thyroid-stimulating hormone (TSH), is
released under the influence
of hypothalamic thyrotropin-releasing
hormone (TRH) and is inhibited by
somatostatin.
• 3 - Corticotropins:
Adrenocorticotropic hormone (ACTH),
and Beta-endorphin are released under the
influence of hypothalamic corticotropin-
releasing hormone (CRH).
• 4 - Lactotrophins:
• Prolactin (PRL), whose release is
inconsistently stimulated by hypothalamic
TRH, oxytocin, vasopressin, and inhibited
by hypothalamic dopamine.
• 5 - Gonadotropins:
• Luteinizing hormone (also referred to as
'Lutropin' or 'LH').
• Follicle-stimulating hormone (FSH), both
released under influence of Gonadotropin-
Releasing Hormone (GnRH)
• These hormones are released from
the anterior pituitary under the
influence of the hypothalamus.
Hypothalamic hormones are secreted
to the anterior lobe by way of a
special capillary system .
• The Posterior pituitary
• The posterior pituitary stores and secretes
(not synthesize) the following important
endocrine hormones:
1 - Antidiuretic hormone (ADH, also known
as vasopressin and arginine vasopressin
AVP).
2 – Oxytocin .
Functions
• Hormones secreted from the pituitary gland
help control the following body processes:
• Growth
• Blood pressure
• Some aspects of pregnancy and childbirth
including stimulation of uterine contractions
during childbirth
• Breast milk production
• Sex organ functions in both males and females
• Thyroid gland function .
• The conversion of food into energy
(metabolism) .
• Water and osmolarity regulation in the body .
• Water balance via the control of reabsorption
of water by the kidneys .
• Temperature regulation .
• Pain relief .
Hypothalamus
• is a portion of the brain that contains
a number of small nuclei with a
variety of functions. One of the most
important functions of the
hypothalamus is to link the nervous
system to the endocrine system via
the pituitary gland (hypophysis).
The hypothalamus controls
• Body temperature.
• Hunger.
• Important aspects of parenting and
attachment behaviors.
• Thirst.
• Fatigue.
• Sleep.
• And circadian rhythms.
Hormones
• Hormones are chemical
messengers that are secreted
directly into the blood, which
carries them to organs and
tissues of the body to exert their
functions. Hormones are
secreted from the endocrine
glands in the body.
• The glands are ductless, so
hormones are secreted directly into
the blood stream rather than by way
of ducts.
Hormonal Regulation
• Regulating hormones means controlling
how much hormones are made and
released from cells.
• Hormones secretion is regulated through
the hypothalamus and pituitary which
regulate their own secretion through
negative feedback inhibition.
• Negative feedback occurs when the rate
of the process decreases as the
concentration of the product increases.
• Negative feedback leads to hormone
production switching on and off, creating
pulses of hormone secretion. This means
that blood hormone levels rise and fall
cyclically, within a relatively narrow
normal range.
• What this means is that a hormone from
a peripheral gland, binds to its receptor
on cells in the hypothalamus and
pituitary, and has the effect of inhibiting
secretion of tropic hormones.
• The usefulness of negative feedback
inhibition is that it results in "hormonal
homeostasis", that is the maintenance of
hormone levels within a particular
appropriate physiological range.
• An example of negative feedback in the
endocrine system can be seen in the
regulation of thyroid hormones.
• It starts with the brain's hypothalamus,
which produces thyroid releasing
hormone (TRH).
• This hormone moves to the nearby
pituitary gland, causing production of
thyroid stimulating hormone (TSH), which
is then released into the blood stream.
• On reaching the thyroid, TSH stimulates
the cells there to now secrete thyroid
hormones.
• When the level of thyroid hormones in
the blood reaches an upper threshold,
the cells in the hypothalamus that make
and secrete TRH are affected.
• The result is that TRH, then TSH, and
finally thyroid hormone levels fall.
• Once the level of thyroid hormones in
the blood falls below a lower threshold
point, negative feedback ends.
•
• ( In negative feedback, the hormone's
effect makes a gland stop making
hormones ) .
Positive feedback
• occurs when the rate of a process
increases as the concentration of the
product decreases.
• In positive feedback the opposite
happens. The effect of the hormone tells
the gland to make even more hormones.
• One example of a biological positive
feedback loop is the onset of contractions
in childbirth.
• When a contraction occurs, the hormone
oxytocin is released into the body, which
stimulates further contractions.
• This results in contractions increasing in
amplitude and frequency.
• Childbirth contractions stop when the
baby is out of the mother's body.
Adrenal gland
• Difintion :
are endocrine glands that sit at the top
of the kidneys; the right adrenal gland
is triangular shaped, while the left
adrenal gland is semilunar shaped.
They secretes hormones directly into
the bloodstream.
• Anatomy and physiology
• An adrenal gland is made of two
parts:
1- Adrenal cortex ,The outer region
which is regulated by neuroendocrine
hormones secreted from the pituitary
gland which are under the control of
the hypothalamus.
• 2 - Adrenal medulla , the inner region
which is part from sympathetic nervous
system .
• adrenal cortex
• The adrenal cortex is responsible for
creating three different types of
hormones:
• A- mineralocorticoids which save sodium
in the body.
• B- glucocorticoids which increase blood
glucose levels.
• C- and gonadocorticoids which
regulate sex hormones such as
estrogen.
• Death would result if the adrenal
cortex were to stop functioning as it
controls metabolic processes that are
essential to life.
• The adrenal cortex include three zones,
or layers ,each zone produce and secrete
distinct hormones:
1- Zona glomerulosa (outer) is the main
site for production and secretion of
mineralocorticoid mainly aldosterone .
2- Zona fasciculate ( middle )
,responsible for producing glucocorticoids
mainly cortisol .
• 3- Zona reticularis ( inner ) zona
reticularis produces androgens, mainly
dehydroepiandrosterone (DHEA) .
Glucocorticoids
•Cortisol
• Is the main glucocorticoid under normal
conditions it is also Called “the stress
hormone,” .
• When you faced a threat — your
hypothalamus, sets off an alarm system
in your body.
• Through a combination of nerve and
hormonal signals, this system induce
your adrenal glands, to release a surge of
hormones, including adrenaline and
cortisol.
• Adrenaline increases your heart rate,
elevates your blood pressure and
increase energy supplies.
• Cortisol, the primary stress hormone,
increases sugars (glucose) in the
bloodstream.
• Enhances your brain's use of glucose .
• And increases the availability of
substances that repair tissues .
• The body's stress-response system is
usually self-limiting. Once the threat has
passed, hormone levels return to normal.
• As adrenaline and cortisol levels drop,
your heart rate and blood pressure return
to baseline levels, and other systems
resume their regular activities.
Function of Cortisol
• cortisol influences, regulates or
modulates many of the changes that
occur in the body in response to stress
including :
1 - Blood sugar (glucose) levels.
plays an important role in (glycogenolysis ),
the breaking down of glycogen to glucose-
1-phosphate and glucose, in liver and
muscle tissue.
2 - Fat, and protein metabolism to maintain
blood glucose (gluconeogenesis) .
3 - It reduces protein uptake
(those proteins are used in
gluconeogenesis) by the muscles.
So, if cortisol is around for long periods of
time, it can lead to a reduction in lean
muscle mass.
4 - Immune responses .
5 - Anti-inflammatory actions (Has anti-
inflammatory properties, reducing
histamine secretion ) .
6 - Blood pressure (Increases blood
pressure by increasing the sensitivity of the
vasculature to epinephrine and
norepinephrine; in the absence of cortisol,
widespread vasodilation occurs ) .
7 - Heart and blood vessel tone and
contraction .
8 - Central nervous system activation .
9 - Cortisol also reduces calcium absorption
in the intestine so it reduces bone
formation .
10 - It acts as antidiuretic hormone,
controlling one-half of intestinal diuresis .
11 -There are potential links between
cortisol, appetite, and obesity.
12 - Additionally, cortisol enhances the
activity of other hormones including
glucagon and catecholamines.
Patterns
• Cortisol levels normally fluctuate
throughout the day and night in a
circadian rhythm that peaks at about 8
AM and reaches it lowest around lowest
levels are at about midnight.
• They drop very low in the evening and
during the early phase of sleep. But if you
sleep during the day and are up at night,
this pattern may be reversed.
• If you do not have this daily change
(diurnal rhythm) in cortisol levels, you
may have overactive adrenal glands. This
condition is called Cushing's syndrome.
• While it is vital to health for the adrenals
to secret more cortisol in response to
stress, it is also very important that bodily
functions and cortisol levels return to
normal following a stressful event.
• Unfortunately, in our current high-stress
culture, the stress response is activated
so often that the body does not always
have a chance to return to normal.*
• This can lead to health problems resulting
from too much circulating cortisol and/or
from too little cortisol if the adrenal
glands become chronically fatigued
(adrenal fatigue).
Binding
• Most serum cortisol (all but about 4%) is
bound to proteins, including
corticosteroid binding globulin (CBG) and
serum albumin. Free cortisol passes
easily through cellular membranes,
where they bind intracellular cortisol
receptors . The "free" is biologically
active.
• Free cortisol is excreted into the urine
and is present in the saliva.
• The test measures the amount of cortisol
in the blood, urine, or saliva.
• Small increases of cortisol have some
positive effects:
1 - A quick burst of energy for survival
reasons .
2 – increases memory functions .
3 - A burst of increased immunity .
4 - Lower sensitivity to pain .
5 -Helps maintain homeostasis in the body
• Higher and more prolonged levels of
cortisol in the bloodstream (like those
associated with chronic stress) have been
shown to have negative effects, such as:
1 - Impaired cognitive performance .
2 - Suppressed thyroid function .
3 - Blood sugar imbalances such as
hyperglycemia .
4 - Decreased bone density .
5 - Decrease in muscle tissue .
6 - Higher blood pressure .
7 - Lowered immunity and inflammatory
responses in the body, slowed wound
healing, and other health consequences .
8 - Increased abdominal fat, which is
associated with a greater amount of health
problems than fat deposited in other areas
of the body.
Some of the health problems associated
with increased stomach fat are heart
attacks, strokes, the development of
metabolic syndrome, higher levels of “bad”
cholesterol (LDL) and lower levels of
“good” cholesterol (HDL), which can lead to
other health problems!
• Cortisol is synthesized from cholesterol ,
Synthesis takes place in zona fasciculata
of the adrenal cortex .
• The synthesis of cortisol in the adrenal
gland is stimulated by the anterior lobe of
the pituitary gland with
adrenocorticotropic hormone (ACTH) .
• ACTH production is in turn stimulated by
corticotropin-releasing hormone (CRH),
which is released by the hypothalamus.
• Disorders of cortisol production , whether
( increased or decreased ) will cause :
• Anxiety .
• Depression .
• Digestive problems .
• Heart disease .
• Sleep problems .
• Weight gain .
• Memory and concentration impairment .
: Excessive levels of cortisol in
the blood.
• Cushing's syndrome
• Is a group of signs and symptoms caused
by abnormally high levels of cortisol
(hypercortisolism).
• Signs and symptoms associated with
Cushing syndrome vary but frequently
include:
• Obesity in the trunk (central obesity) with
thinner arms and legs .
• A large rounded face (moon face) .
• Increased fat in the neck and shoulder
area .
• Thirst and excessive urination .
• Visual problems .
• Increased susceptibility to infections .
• Thin, fragile skin that bruises easily and
heals slowly .
• Pinkish streaks that look like stretch
marks on the abdomen, thighs, and
buttocks .
• Muscle weakness .
• Decreased endurance .
• Osteoporosis .
• High blood pressure .
• Increased blood sugar .
• Headaches, backaches .
• Children with Cushing syndrome tend to
be obese, develop slowly, and may
remain short.
• Women may have excess hair on their
face and chest and menstrual
irregularities.
Common causes of Cushing syndrome
1 - Prolonged glucocorticoid therapy
(iatrogenic Cushing syndrome) -- a result of
taking glucocorticoids-steroid hormones
that are chemically similar to natural
cortisol, such as anti-inflammatory
medications like prednisone prescribed for
asthma, rheumatoid arthritis, lupus, and
other inflammatory diseases, or after an
organ transplant to suppress the immune
system and prevent organ rejection.
2 - Cushing disease -- caused by a pituitary
gland that produces too much of the
hormone ACTH, which then signals the
adrenal glands to produce cortisol.
• It is caused by a pituitary tumor
(adenoma) that secretes ACTH.
3 - An adrenal gland tumor or adrenal
hyperplasia can cause the adrenal gland to
overproduce cortisol.
4 - A tumor in another part of the body
such as the pancreas, lung, or thyroid can
produce ACTH (called "ectopic" ACTH
production because it is produced
somewhere other than the pituitary gland).
• Cushing syndrome can affect anyone, but
it is most frequently seen in adults
between the ages of 20 to 50 years .
• It is 3 times more common in women
than men.
• It is estimated that there are two new
cases per million people each year.
• No single laboratory test is ideal to
diagnose Cushing syndrome and more
than one is often used. Since cortisol
levels change over the course of a day, a
single cortisol result from a blood sample
drawn at most times of the day is of little
value.
• Testing for Cushing syndrome is typically
done in two stages. Initial tests are used
to verify that there is excess cortisol
present. The second set of tests is used to
determine the cause of the increased
cortisol: pituitary, adrenal, or other.
• Initial tests to diagnosis Cushing
syndrome
• The three most common tests are :
1 - Measurement of midnight plasma
cortisol or late-night salivary cortisol .
2 - 24-hour urinary free cortisol test .
3 - The dexamethasone suppression
screening test .
• Adrenal Insufficiency and Addison Disease
( )
• They are hormonal or endocrine
disorders caused by the body not
producing enough of the adrenal
hormones cortisol and aldosterone.
• There are two different types of adrenal
insufficiency and they depend on
whether pituitary gland or adrenal
dysfunction underlies hormone
deficiencies,they are :
1 - Underactive or damaged adrenal glands
cause Addison disease, also known as
primary adrenal insufficiency.
• They affect cortisol and aldosterone
amounts.
2 - Decrease in the production of the
pituitary hormone ACTH is at the root of
secondary adrenal insufficiency.
• If there is insufficient ACTH, due to
pituitary damage, a pituitary tumor, or
some other cause, then cortisol
production is not stimulated.
• Secondary adrenal insufficiency can also
arise when corticosteroid therapy (such
as prednisone, which may be given to
relieve inflammation ) ,These treatments
suppress natural cortisol production and
it can take several weeks or months for
normal production to resume.
• Fcats about Cortisol under production
• Addison disease is found in people of all
ages and affects both males and females
equally.
• Symptoms of insufficiency may not arise
until about 80% to 90% of the adrenal
cortex has been destroyed.
May include:
• Low blood pressure .
• Hyponatremia, with Addison disease .
• Hypoglycemia .
• Hyperkalemia .
• Abdominal pain .
• Decreased body hair .
• Dehydration, with Addison disease .
• Diarrhea or constipation .
• Dizziness and fainting .
• Fatigue or extreme weakness .
• Hyperpigmentation, with Addison disease
- dark spot of skin, especially in the folds
of the skin; sometime black freckles on
the forehead and face .
• Salt craving, with Addison disease .
• Changes in blood pressure or heart rate .
• Muscle weakness .
• Vomiting .
• Weight loss .
1 - Cortisol.
ACTH .
3 – Aldosterone .
4 - Electrolytes .
• They are a class of steroid hormones
characterized by their influence on salt
and water balances.
• These hormones were involved in the
retention of sodium .
• „Acutely critical for maintenance of life .
• „The primary mineralocorticoid is
aldosterone.
• Loss of mineralocorticoid activity
• „Elevated concentration of potassium in
extracellular fluid .
• „High urinary excretion of sodium .
• „Decreased concentration of sodium in
extracellular fluid .
• „Decreased volume of extracellular fluid
and blood .
• „Decline of cardiac output and shock .
• Good news
• „All those symptoms can largely be prevented
by .
• replacement of salts and mineralocorticoids .
• Is a steroid hormone produced from
cholesterol by the outer section (zona
glomerulosa) of the adrenal cortex in the
adrenal gland .
• It plays a central role in the regulation of
blood pressure mainly by acting on the
distal tubules and collecting ducts of the
nephron.
• „20% bound to cortisol-binding protein .
• „40% albumin-bound .
• „40% free .
• „Half-life 20 min .
• „Liver .
• „Free hormone filtered by kidneys .
•
• Aldosterone stimulates transcription of
the gene encoding the sodium-potassium
ATPase, leading to increased numbers of
"sodium pumps" in the membranes of
tubular cells.
• Aldosterone also stimulates a sodium
channel which facilitates uptake of
sodium from the tubular lumen.
• Aldosterone has also effects on sweat
glands, salivary glands and the colon
which are essentially identical to those
seen in the distal tubule of the kidney.
• The major net effect is again to conserve
body sodium by stimulating its resorption
or, in the case of the colon, absorption
from the intestinal lumen.
1 -The role of the renin-angiotensin system
2 - The plasma concentration of potassium
„3 - ACTH .
„4 - Atrial Natriuretic Peptide( suppress
aldosterone ).
• By overactivity of both glands called
bilateral adrenal hyperplasia.
• Or for unknown reasons (idiopathic).
• Rarely, it is caused by a cancerous
(malignant) adrenal tumor .
 The high aldosterone level will CAUSE:
increases reabsorption of sodium (salt) .
loss of potassium by the kidneys.
an electrolyte imbalance .
• include
• High blood pressure.
• Headache.
• And muscle weakness, espeically if
potassium levels are very low.
Lower than normal blood potassium
(hypokalemia) in someone with
hypertension suggests the need to look
for aldosteronism.
• In Conn syndrome, aldosterone is
produced despite low renin levels.
• Sometimes, to determine whether only
one or both adrenal glands are affected,
blood may be taken from both of the
adrenal veins and testing is done to
determine whether there is a difference
in the amount of aldosterone (and
sometimes cortisol) produced by each of
the adrenal glands.
2 -
which is more common than primary
aldosteronism, is caused by anything that
leads to excess aldosterone, other than a
disorder of the adrenal glands.
• It could be caused by any condition that
• decreases blood flow to the kidneys.
• decreases blood pressure.
• or lowers sodium levels.
• Congestive heart failure .
• liver Cirrhosis .
• Kidney disease .
• And toxemia of pregnancy
(preeclampsia) .
In these conditions, the cause of
aldosteronism is usually obvious .
• The most important cause of seconary
aldosteronism is narrowing of the blood
vessels that supply the kidney, termed
(renal artery stenosis ).
• This causes high blood pressure due to
high renin and aldosterone .
DISEASE ALDOSTERONE RENIN
Primary aldosteronism
(Conn syndrome)
High Low
Secondary aldosteronism High High
Secondary aldosteronism must be distinguished from primary
aldosteronism. Secondary aldosteronism is not the same as
Conn syndrome because renin levels are high in secondary
aldosteronism.
• „Na+ retention → hypernatremia → EC volume↑↑
→BP↑↑
• „K+ depletion → hypokalemia → damages kidneys
and also muscle weakness
• „H+ depletion → alkalosis → plasma Ca++↓ →
muscle cramp
Hypoaldosteronism (Low aldosterone)
Usually occurs as part of adrenal
insufficiency; it causes
Dehydration.
 low blood pressure.
 low blood sodium level.
And a high potassium level.
• Is there anything else I should know?
• The amount of salt in your diet and
medications, such as over-the-counter
pain relievers of the non-steroid class,
diuretics, beta blockers, steroids,
angiotensin-converting enzyme (ACE)
inhibitors, and oral contraceptives can
affect the test results. Some of these
drugs are used to treat high blood
pressure.
• Stress, exercise, and pregnancy can also
affect the test results.
• Coffee, tea or cola can affect the 24-hour
urine sample test .
• The body's position .
• Both aldosterone and renin levels are
highest in the morning and vary
throughout the day.
• Aldosterone levels become very low with
severe illness, so testing should not be
done at times when someone is very ill.
catecholamines
Epinephrine (adrenaline), and
norepinephrine (noradrenaline)
• It is part of the adrenal gland.
• It is located at the center of the gland,
being surrounded by the adrenal cortex.
• It is consisting of cells that secrete
epinephrine (adrenaline), norepinephrine
(noradrenaline), and a small amount of
dopamine in response to stimulation by
the central nervous system .
Adrenal medulla Is the principal site of
the conversion of the amino acid tyrosine
into the catecholamines .
 The hormone release In response to
stressors such as exercise or danger.
medullary cells release catecholamines
into the blood in a 15:3 ratio of
adrenaline to noradrenaline.
 Release of catecholamines is stimulated
by nerve impulses, and receptors for
catecholamines are widely distributed
throughout the body.
 Effects of adrenaline and noradrenaline
include
# Increased heart rate and blood pressure.
#Blood vessel constriction in the skin and
gastrointestinal tract.
# Smooth muscle (bronchiole and
capillary) dilation.
# And increased metabolism, all of which
are characteristic of the fight-or-flight
response.
• The human adrenal medulla produces
and releases about 80% epinephrine and
20% norepinephrine, with a small
amount of dopamine.
• While the adrenergic neurons are
responsible for the majority of
norepinephrine production, the adrenal
is the source of essentially all of the
epinephrine produced in the body .
• 3 - In skeletal muscle, epinephrine also
stimulates glycogen breakdown .
• The effect of epinephrine in muscle is a
preparation for the requirement of
exercise – without exercise, the increase
in glycolysis in muscle is fairly limited.
• 4 - In adipose tissue, epinephrine
stimulates lipolysis by increasing the
activity of hormone-sensitive lipase.
Epinephrine and norepinephrine decrease
pancreatic production of insulin .
This reduction of insulin secretion may
also protect
the pancreas from exhaustion in conditions
of chronic stress, by reducing the necessity
for insulin production to compete with
production of adrenal hormones.
• This is potentially important, because,
unlike the adrenal, which responds to
increased requirement for its hormones
by increasing its ability to produce those
hormones, the pancreas has only a
limited capacity for increasing insulin
secretion rates.
• There are no direct clinical consequences
of adrenal medullary insufficiency.
• An adrenal disorder patient’s requires
supplementation with glucocorticoids
and mineralocorticoids, but suffers no
apparent ill effects from lack of
epinephrine.
• The reason for this is unknown.
• It is possible that norepinephrine release
from the sympathetic nervous system
yields sufficient circulating catecholamine
to maintain normal functioning.
• Alternatively, other systems have
somewhat similar effects, especially on
glucose homeostasis, and these other
systems may compensate for lack of
epinephrine.
• Uncontrolled excessively high levels of
catecholamines are usually the result of a
relatively rare tumor of the chromaffin
cells called a pheochromocytoma.
• These tumors may occur in the adrenal.
• A pheochromocytoma may release
catecholamines continually .
•
hypothalamus , pituitary and adrenal glands

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hypothalamus , pituitary and adrenal glands

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  • 6. • Difintion : • The pituitary is an endocrine (hormone-producing) gland that sits just beneath the base of the brain, behind the bridge of the nose. • It is very small – only about the size of a pea , and weighing 0.5 grams .
  • 7. • It is very important as it takes messages from the brain (via a gland called the hypothalamus) and uses these messages to produce hormones that affect many parts of the body, including stimulating all the other hormone-producing glands to produce their own hormones. For this reason it is often referred to as the ‘master gland’.
  • 8. • It is composed of three lobes: • anterior, intermediate, and posterior.
  • 9.
  • 10. Hormones secreted • The anterior pituitary • synthesizes and secretes the following important endocrine hormones. All releasing hormones (- RH) referred to, can also be referred to as releasing factors (-RF ) . • 1-Somatotrophins: • Human growth hormone (HGH), also referred to as 'growth hormone' (GH) , and also as somatotropin, is released under the influence of hypothalamic growth hormone-releasing hormone(GHRH), and is inhibited by hypothalamic somatostatin
  • 11. • 2- Thyrotrophins: • Thyroid-stimulating hormone (TSH), is released under the influence of hypothalamic thyrotropin-releasing hormone (TRH) and is inhibited by somatostatin. • 3 - Corticotropins: Adrenocorticotropic hormone (ACTH), and Beta-endorphin are released under the influence of hypothalamic corticotropin- releasing hormone (CRH).
  • 12. • 4 - Lactotrophins: • Prolactin (PRL), whose release is inconsistently stimulated by hypothalamic TRH, oxytocin, vasopressin, and inhibited by hypothalamic dopamine. • 5 - Gonadotropins: • Luteinizing hormone (also referred to as 'Lutropin' or 'LH'). • Follicle-stimulating hormone (FSH), both released under influence of Gonadotropin- Releasing Hormone (GnRH)
  • 13. • These hormones are released from the anterior pituitary under the influence of the hypothalamus. Hypothalamic hormones are secreted to the anterior lobe by way of a special capillary system .
  • 14. • The Posterior pituitary • The posterior pituitary stores and secretes (not synthesize) the following important endocrine hormones: 1 - Antidiuretic hormone (ADH, also known as vasopressin and arginine vasopressin AVP). 2 – Oxytocin .
  • 15. Functions • Hormones secreted from the pituitary gland help control the following body processes: • Growth • Blood pressure • Some aspects of pregnancy and childbirth including stimulation of uterine contractions during childbirth • Breast milk production
  • 16. • Sex organ functions in both males and females • Thyroid gland function . • The conversion of food into energy (metabolism) . • Water and osmolarity regulation in the body . • Water balance via the control of reabsorption of water by the kidneys . • Temperature regulation . • Pain relief .
  • 17. Hypothalamus • is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland (hypophysis).
  • 18.
  • 19. The hypothalamus controls • Body temperature. • Hunger. • Important aspects of parenting and attachment behaviors. • Thirst. • Fatigue. • Sleep. • And circadian rhythms.
  • 20. Hormones • Hormones are chemical messengers that are secreted directly into the blood, which carries them to organs and tissues of the body to exert their functions. Hormones are secreted from the endocrine glands in the body.
  • 21. • The glands are ductless, so hormones are secreted directly into the blood stream rather than by way of ducts.
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  • 25. Hormonal Regulation • Regulating hormones means controlling how much hormones are made and released from cells. • Hormones secretion is regulated through the hypothalamus and pituitary which regulate their own secretion through negative feedback inhibition.
  • 26. • Negative feedback occurs when the rate of the process decreases as the concentration of the product increases. • Negative feedback leads to hormone production switching on and off, creating pulses of hormone secretion. This means that blood hormone levels rise and fall cyclically, within a relatively narrow normal range.
  • 27.
  • 28. • What this means is that a hormone from a peripheral gland, binds to its receptor on cells in the hypothalamus and pituitary, and has the effect of inhibiting secretion of tropic hormones. • The usefulness of negative feedback inhibition is that it results in "hormonal homeostasis", that is the maintenance of hormone levels within a particular appropriate physiological range.
  • 29. • An example of negative feedback in the endocrine system can be seen in the regulation of thyroid hormones. • It starts with the brain's hypothalamus, which produces thyroid releasing hormone (TRH). • This hormone moves to the nearby pituitary gland, causing production of thyroid stimulating hormone (TSH), which is then released into the blood stream.
  • 30. • On reaching the thyroid, TSH stimulates the cells there to now secrete thyroid hormones. • When the level of thyroid hormones in the blood reaches an upper threshold, the cells in the hypothalamus that make and secrete TRH are affected.
  • 31. • The result is that TRH, then TSH, and finally thyroid hormone levels fall. • Once the level of thyroid hormones in the blood falls below a lower threshold point, negative feedback ends.
  • 33. • ( In negative feedback, the hormone's effect makes a gland stop making hormones ) .
  • 34.
  • 35. Positive feedback • occurs when the rate of a process increases as the concentration of the product decreases. • In positive feedback the opposite happens. The effect of the hormone tells the gland to make even more hormones.
  • 36. • One example of a biological positive feedback loop is the onset of contractions in childbirth. • When a contraction occurs, the hormone oxytocin is released into the body, which stimulates further contractions. • This results in contractions increasing in amplitude and frequency. • Childbirth contractions stop when the baby is out of the mother's body.
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  • 40. Adrenal gland • Difintion : are endocrine glands that sit at the top of the kidneys; the right adrenal gland is triangular shaped, while the left adrenal gland is semilunar shaped. They secretes hormones directly into the bloodstream.
  • 41. • Anatomy and physiology • An adrenal gland is made of two parts: 1- Adrenal cortex ,The outer region which is regulated by neuroendocrine hormones secreted from the pituitary gland which are under the control of the hypothalamus.
  • 42. • 2 - Adrenal medulla , the inner region which is part from sympathetic nervous system .
  • 43. • adrenal cortex • The adrenal cortex is responsible for creating three different types of hormones: • A- mineralocorticoids which save sodium in the body. • B- glucocorticoids which increase blood glucose levels.
  • 44. • C- and gonadocorticoids which regulate sex hormones such as estrogen. • Death would result if the adrenal cortex were to stop functioning as it controls metabolic processes that are essential to life.
  • 45. • The adrenal cortex include three zones, or layers ,each zone produce and secrete distinct hormones: 1- Zona glomerulosa (outer) is the main site for production and secretion of mineralocorticoid mainly aldosterone . 2- Zona fasciculate ( middle ) ,responsible for producing glucocorticoids mainly cortisol .
  • 46. • 3- Zona reticularis ( inner ) zona reticularis produces androgens, mainly dehydroepiandrosterone (DHEA) .
  • 47. Glucocorticoids •Cortisol • Is the main glucocorticoid under normal conditions it is also Called “the stress hormone,” . • When you faced a threat — your hypothalamus, sets off an alarm system in your body.
  • 48. • Through a combination of nerve and hormonal signals, this system induce your adrenal glands, to release a surge of hormones, including adrenaline and cortisol. • Adrenaline increases your heart rate, elevates your blood pressure and increase energy supplies.
  • 49. • Cortisol, the primary stress hormone, increases sugars (glucose) in the bloodstream. • Enhances your brain's use of glucose . • And increases the availability of substances that repair tissues .
  • 50. • The body's stress-response system is usually self-limiting. Once the threat has passed, hormone levels return to normal. • As adrenaline and cortisol levels drop, your heart rate and blood pressure return to baseline levels, and other systems resume their regular activities.
  • 51. Function of Cortisol • cortisol influences, regulates or modulates many of the changes that occur in the body in response to stress including : 1 - Blood sugar (glucose) levels. plays an important role in (glycogenolysis ), the breaking down of glycogen to glucose- 1-phosphate and glucose, in liver and muscle tissue.
  • 52. 2 - Fat, and protein metabolism to maintain blood glucose (gluconeogenesis) . 3 - It reduces protein uptake (those proteins are used in gluconeogenesis) by the muscles. So, if cortisol is around for long periods of time, it can lead to a reduction in lean muscle mass.
  • 53. 4 - Immune responses . 5 - Anti-inflammatory actions (Has anti- inflammatory properties, reducing histamine secretion ) . 6 - Blood pressure (Increases blood pressure by increasing the sensitivity of the vasculature to epinephrine and norepinephrine; in the absence of cortisol, widespread vasodilation occurs ) .
  • 54. 7 - Heart and blood vessel tone and contraction . 8 - Central nervous system activation . 9 - Cortisol also reduces calcium absorption in the intestine so it reduces bone formation . 10 - It acts as antidiuretic hormone, controlling one-half of intestinal diuresis . 11 -There are potential links between cortisol, appetite, and obesity.
  • 55. 12 - Additionally, cortisol enhances the activity of other hormones including glucagon and catecholamines.
  • 56. Patterns • Cortisol levels normally fluctuate throughout the day and night in a circadian rhythm that peaks at about 8 AM and reaches it lowest around lowest levels are at about midnight. • They drop very low in the evening and during the early phase of sleep. But if you sleep during the day and are up at night, this pattern may be reversed.
  • 57. • If you do not have this daily change (diurnal rhythm) in cortisol levels, you may have overactive adrenal glands. This condition is called Cushing's syndrome.
  • 58. • While it is vital to health for the adrenals to secret more cortisol in response to stress, it is also very important that bodily functions and cortisol levels return to normal following a stressful event. • Unfortunately, in our current high-stress culture, the stress response is activated so often that the body does not always have a chance to return to normal.*
  • 59. • This can lead to health problems resulting from too much circulating cortisol and/or from too little cortisol if the adrenal glands become chronically fatigued (adrenal fatigue).
  • 60. Binding • Most serum cortisol (all but about 4%) is bound to proteins, including corticosteroid binding globulin (CBG) and serum albumin. Free cortisol passes easily through cellular membranes, where they bind intracellular cortisol receptors . The "free" is biologically active.
  • 61. • Free cortisol is excreted into the urine and is present in the saliva. • The test measures the amount of cortisol in the blood, urine, or saliva.
  • 62. • Small increases of cortisol have some positive effects: 1 - A quick burst of energy for survival reasons . 2 – increases memory functions . 3 - A burst of increased immunity . 4 - Lower sensitivity to pain . 5 -Helps maintain homeostasis in the body
  • 63. • Higher and more prolonged levels of cortisol in the bloodstream (like those associated with chronic stress) have been shown to have negative effects, such as: 1 - Impaired cognitive performance . 2 - Suppressed thyroid function . 3 - Blood sugar imbalances such as hyperglycemia . 4 - Decreased bone density .
  • 64. 5 - Decrease in muscle tissue . 6 - Higher blood pressure . 7 - Lowered immunity and inflammatory responses in the body, slowed wound healing, and other health consequences .
  • 65. 8 - Increased abdominal fat, which is associated with a greater amount of health problems than fat deposited in other areas of the body. Some of the health problems associated with increased stomach fat are heart attacks, strokes, the development of metabolic syndrome, higher levels of “bad” cholesterol (LDL) and lower levels of “good” cholesterol (HDL), which can lead to other health problems!
  • 66. • Cortisol is synthesized from cholesterol , Synthesis takes place in zona fasciculata of the adrenal cortex . • The synthesis of cortisol in the adrenal gland is stimulated by the anterior lobe of the pituitary gland with adrenocorticotropic hormone (ACTH) .
  • 67. • ACTH production is in turn stimulated by corticotropin-releasing hormone (CRH), which is released by the hypothalamus.
  • 68. • Disorders of cortisol production , whether ( increased or decreased ) will cause : • Anxiety . • Depression . • Digestive problems . • Heart disease . • Sleep problems . • Weight gain . • Memory and concentration impairment .
  • 69. : Excessive levels of cortisol in the blood. • Cushing's syndrome • Is a group of signs and symptoms caused by abnormally high levels of cortisol (hypercortisolism).
  • 70. • Signs and symptoms associated with Cushing syndrome vary but frequently include: • Obesity in the trunk (central obesity) with thinner arms and legs . • A large rounded face (moon face) . • Increased fat in the neck and shoulder area .
  • 71. • Thirst and excessive urination . • Visual problems . • Increased susceptibility to infections . • Thin, fragile skin that bruises easily and heals slowly . • Pinkish streaks that look like stretch marks on the abdomen, thighs, and buttocks . • Muscle weakness .
  • 72. • Decreased endurance . • Osteoporosis . • High blood pressure . • Increased blood sugar . • Headaches, backaches . • Children with Cushing syndrome tend to be obese, develop slowly, and may remain short. • Women may have excess hair on their face and chest and menstrual irregularities.
  • 73. Common causes of Cushing syndrome 1 - Prolonged glucocorticoid therapy (iatrogenic Cushing syndrome) -- a result of taking glucocorticoids-steroid hormones that are chemically similar to natural cortisol, such as anti-inflammatory medications like prednisone prescribed for asthma, rheumatoid arthritis, lupus, and other inflammatory diseases, or after an organ transplant to suppress the immune system and prevent organ rejection.
  • 74. 2 - Cushing disease -- caused by a pituitary gland that produces too much of the hormone ACTH, which then signals the adrenal glands to produce cortisol. • It is caused by a pituitary tumor (adenoma) that secretes ACTH. 3 - An adrenal gland tumor or adrenal hyperplasia can cause the adrenal gland to overproduce cortisol.
  • 75. 4 - A tumor in another part of the body such as the pancreas, lung, or thyroid can produce ACTH (called "ectopic" ACTH production because it is produced somewhere other than the pituitary gland).
  • 76. • Cushing syndrome can affect anyone, but it is most frequently seen in adults between the ages of 20 to 50 years . • It is 3 times more common in women than men. • It is estimated that there are two new cases per million people each year.
  • 77. • No single laboratory test is ideal to diagnose Cushing syndrome and more than one is often used. Since cortisol levels change over the course of a day, a single cortisol result from a blood sample drawn at most times of the day is of little value.
  • 78. • Testing for Cushing syndrome is typically done in two stages. Initial tests are used to verify that there is excess cortisol present. The second set of tests is used to determine the cause of the increased cortisol: pituitary, adrenal, or other.
  • 79. • Initial tests to diagnosis Cushing syndrome • The three most common tests are : 1 - Measurement of midnight plasma cortisol or late-night salivary cortisol . 2 - 24-hour urinary free cortisol test . 3 - The dexamethasone suppression screening test .
  • 80.
  • 81.
  • 82.
  • 83.
  • 84. • Adrenal Insufficiency and Addison Disease ( ) • They are hormonal or endocrine disorders caused by the body not producing enough of the adrenal hormones cortisol and aldosterone.
  • 85. • There are two different types of adrenal insufficiency and they depend on whether pituitary gland or adrenal dysfunction underlies hormone deficiencies,they are : 1 - Underactive or damaged adrenal glands cause Addison disease, also known as primary adrenal insufficiency. • They affect cortisol and aldosterone amounts.
  • 86. 2 - Decrease in the production of the pituitary hormone ACTH is at the root of secondary adrenal insufficiency. • If there is insufficient ACTH, due to pituitary damage, a pituitary tumor, or some other cause, then cortisol production is not stimulated.
  • 87. • Secondary adrenal insufficiency can also arise when corticosteroid therapy (such as prednisone, which may be given to relieve inflammation ) ,These treatments suppress natural cortisol production and it can take several weeks or months for normal production to resume.
  • 88. • Fcats about Cortisol under production • Addison disease is found in people of all ages and affects both males and females equally. • Symptoms of insufficiency may not arise until about 80% to 90% of the adrenal cortex has been destroyed.
  • 89. May include: • Low blood pressure . • Hyponatremia, with Addison disease . • Hypoglycemia . • Hyperkalemia . • Abdominal pain . • Decreased body hair .
  • 90. • Dehydration, with Addison disease . • Diarrhea or constipation . • Dizziness and fainting . • Fatigue or extreme weakness . • Hyperpigmentation, with Addison disease - dark spot of skin, especially in the folds of the skin; sometime black freckles on the forehead and face . • Salt craving, with Addison disease .
  • 91. • Changes in blood pressure or heart rate . • Muscle weakness . • Vomiting . • Weight loss .
  • 92. 1 - Cortisol. ACTH . 3 – Aldosterone . 4 - Electrolytes .
  • 93.
  • 94.
  • 95. • They are a class of steroid hormones characterized by their influence on salt and water balances. • These hormones were involved in the retention of sodium . • „Acutely critical for maintenance of life . • „The primary mineralocorticoid is aldosterone.
  • 96. • Loss of mineralocorticoid activity • „Elevated concentration of potassium in extracellular fluid . • „High urinary excretion of sodium . • „Decreased concentration of sodium in extracellular fluid . • „Decreased volume of extracellular fluid and blood . • „Decline of cardiac output and shock .
  • 97. • Good news • „All those symptoms can largely be prevented by . • replacement of salts and mineralocorticoids .
  • 98. • Is a steroid hormone produced from cholesterol by the outer section (zona glomerulosa) of the adrenal cortex in the adrenal gland . • It plays a central role in the regulation of blood pressure mainly by acting on the distal tubules and collecting ducts of the nephron.
  • 99. • „20% bound to cortisol-binding protein . • „40% albumin-bound . • „40% free . • „Half-life 20 min . • „Liver . • „Free hormone filtered by kidneys .
  • 100.
  • 101. • • Aldosterone stimulates transcription of the gene encoding the sodium-potassium ATPase, leading to increased numbers of "sodium pumps" in the membranes of tubular cells. • Aldosterone also stimulates a sodium channel which facilitates uptake of sodium from the tubular lumen.
  • 102. • Aldosterone has also effects on sweat glands, salivary glands and the colon which are essentially identical to those seen in the distal tubule of the kidney. • The major net effect is again to conserve body sodium by stimulating its resorption or, in the case of the colon, absorption from the intestinal lumen.
  • 103. 1 -The role of the renin-angiotensin system 2 - The plasma concentration of potassium „3 - ACTH . „4 - Atrial Natriuretic Peptide( suppress aldosterone ).
  • 104.
  • 105.
  • 106. • By overactivity of both glands called bilateral adrenal hyperplasia. • Or for unknown reasons (idiopathic). • Rarely, it is caused by a cancerous (malignant) adrenal tumor .
  • 107.  The high aldosterone level will CAUSE: increases reabsorption of sodium (salt) . loss of potassium by the kidneys. an electrolyte imbalance .
  • 108. • include • High blood pressure. • Headache. • And muscle weakness, espeically if potassium levels are very low. Lower than normal blood potassium (hypokalemia) in someone with hypertension suggests the need to look for aldosteronism.
  • 109. • In Conn syndrome, aldosterone is produced despite low renin levels. • Sometimes, to determine whether only one or both adrenal glands are affected, blood may be taken from both of the adrenal veins and testing is done to determine whether there is a difference in the amount of aldosterone (and sometimes cortisol) produced by each of the adrenal glands.
  • 110. 2 - which is more common than primary aldosteronism, is caused by anything that leads to excess aldosterone, other than a disorder of the adrenal glands. • It could be caused by any condition that • decreases blood flow to the kidneys. • decreases blood pressure. • or lowers sodium levels.
  • 111. • Congestive heart failure . • liver Cirrhosis . • Kidney disease . • And toxemia of pregnancy (preeclampsia) . In these conditions, the cause of aldosteronism is usually obvious .
  • 112. • The most important cause of seconary aldosteronism is narrowing of the blood vessels that supply the kidney, termed (renal artery stenosis ). • This causes high blood pressure due to high renin and aldosterone .
  • 113. DISEASE ALDOSTERONE RENIN Primary aldosteronism (Conn syndrome) High Low Secondary aldosteronism High High Secondary aldosteronism must be distinguished from primary aldosteronism. Secondary aldosteronism is not the same as Conn syndrome because renin levels are high in secondary aldosteronism.
  • 114. • „Na+ retention → hypernatremia → EC volume↑↑ →BP↑↑ • „K+ depletion → hypokalemia → damages kidneys and also muscle weakness • „H+ depletion → alkalosis → plasma Ca++↓ → muscle cramp
  • 115. Hypoaldosteronism (Low aldosterone) Usually occurs as part of adrenal insufficiency; it causes Dehydration.  low blood pressure.  low blood sodium level. And a high potassium level.
  • 116. • Is there anything else I should know? • The amount of salt in your diet and medications, such as over-the-counter pain relievers of the non-steroid class, diuretics, beta blockers, steroids, angiotensin-converting enzyme (ACE) inhibitors, and oral contraceptives can affect the test results. Some of these drugs are used to treat high blood pressure.
  • 117. • Stress, exercise, and pregnancy can also affect the test results. • Coffee, tea or cola can affect the 24-hour urine sample test . • The body's position . • Both aldosterone and renin levels are highest in the morning and vary throughout the day. • Aldosterone levels become very low with severe illness, so testing should not be done at times when someone is very ill.
  • 118.
  • 120. • It is part of the adrenal gland. • It is located at the center of the gland, being surrounded by the adrenal cortex. • It is consisting of cells that secrete epinephrine (adrenaline), norepinephrine (noradrenaline), and a small amount of dopamine in response to stimulation by the central nervous system .
  • 121. Adrenal medulla Is the principal site of the conversion of the amino acid tyrosine into the catecholamines .  The hormone release In response to stressors such as exercise or danger. medullary cells release catecholamines into the blood in a 15:3 ratio of adrenaline to noradrenaline.
  • 122.  Release of catecholamines is stimulated by nerve impulses, and receptors for catecholamines are widely distributed throughout the body.  Effects of adrenaline and noradrenaline include # Increased heart rate and blood pressure. #Blood vessel constriction in the skin and gastrointestinal tract.
  • 123. # Smooth muscle (bronchiole and capillary) dilation. # And increased metabolism, all of which are characteristic of the fight-or-flight response.
  • 124.
  • 125. • The human adrenal medulla produces and releases about 80% epinephrine and 20% norepinephrine, with a small amount of dopamine. • While the adrenergic neurons are responsible for the majority of norepinephrine production, the adrenal is the source of essentially all of the epinephrine produced in the body .
  • 126.
  • 127. • 3 - In skeletal muscle, epinephrine also stimulates glycogen breakdown . • The effect of epinephrine in muscle is a preparation for the requirement of exercise – without exercise, the increase in glycolysis in muscle is fairly limited. • 4 - In adipose tissue, epinephrine stimulates lipolysis by increasing the activity of hormone-sensitive lipase.
  • 128. Epinephrine and norepinephrine decrease pancreatic production of insulin . This reduction of insulin secretion may also protect the pancreas from exhaustion in conditions of chronic stress, by reducing the necessity for insulin production to compete with production of adrenal hormones.
  • 129. • This is potentially important, because, unlike the adrenal, which responds to increased requirement for its hormones by increasing its ability to produce those hormones, the pancreas has only a limited capacity for increasing insulin secretion rates.
  • 130. • There are no direct clinical consequences of adrenal medullary insufficiency. • An adrenal disorder patient’s requires supplementation with glucocorticoids and mineralocorticoids, but suffers no apparent ill effects from lack of epinephrine. • The reason for this is unknown.
  • 131. • It is possible that norepinephrine release from the sympathetic nervous system yields sufficient circulating catecholamine to maintain normal functioning. • Alternatively, other systems have somewhat similar effects, especially on glucose homeostasis, and these other systems may compensate for lack of epinephrine.
  • 132.
  • 133. • Uncontrolled excessively high levels of catecholamines are usually the result of a relatively rare tumor of the chromaffin cells called a pheochromocytoma. • These tumors may occur in the adrenal. • A pheochromocytoma may release catecholamines continually .
  • 134.
  • 135.
  • 136. •