Transcript 1 - ISpatula

Lectures 3 and 4
Ebaa M Alzayadneh, DDS, PhD
Integrative Physiology and Pharmacology
Physiology 2 for pharmacy students
University of Jordan
The Endocrine System
th
Tortora chapter 18,13
ed.
1
Low
blood
glucose
Low
Low
blood
blood
glucose
glucose
111
Lowblood
bloodglucose
glucose
111 Low
Low
blood
glucose
1 Low blood glucose
(hypoglycemia)
(hypoglycemia)
(hypoglycemia)
(hypoglycemia)
(hypoglycemia)
(hypoglycemia)
(hypoglycemia) stimulates
stimulates
release
of
stimulates
release
of
stimulatesrelease
releaseof
of
release
of
stimulates release stimulates
of
Glucose is the main
regulator of GHRH and
GHIH secretion
GH induces IGFs
(Insulin like growth
factors)synthesis and
release.
Actions of IGF:
1- increase protein
synthesis (growth and
proliferation)
2-spares ATP and
glucose
3-glucose production
from fatty acids and
lipolysis not from a.a
GHRH
GHRH
GHRH
GHRH
GHRH
GHRH
GHIH
GHIH
GHRHstimulates
stimulates
GHRH
stimulates
GHRH
stimulates
222222 GHRH
GHRH
stimulates
secretion
secretion
secretion
secretion
secretion
ofhGH
hGHby
by
of
hGH
by
of
hGH
by
of
of
hGH
by
somatotrophs
somatotrophs
somatotrophs
somatotrophs
somatotrophs
hGH
77 GHIH inhibits
secretion of
hGH by
somatotrophs
hGH
hGH
hGH
hGH
hGH
Anterior
Anterior
Anterior
Anterior
pituitary
pituitary
pituitary
pituitary
hGHand
andIGFs
IGFsspeed
speed
hGH
and
IGFs
speed
hGH
and
IGFs
speed
33333 hGH
hGH
and
IGFs
speed
upbreakdown
breakdown
ofliver
liver
up
breakdown
of
liver
up
breakdown
of
liver
up
of
up
breakdown
of
liver
glycogen
into
glucose,
glycogen
into
glucose,
glycogen
into
glucose,
glycogen
into
glycogen
into glucose,
glucose,
whichenters
enters
the
blood
which
enters
the
blood
which
enters
the
blood
which
the
blood
which
enters
the
blood
more
rapidly
more
rapidly
more
rapidly
more
more rapidly
rapidly
A low
low level
level of
of hGH
hGH and
and
88 A
IGFs
decreases
the
rate
IGFs decreases the rate
of glycogen
glycogen breakdown
breakdown
of
in the
the liver
liver and
and glucose
glucose
in
enters the
the blood
blood more
more
enters
slowly
slowly
Bloodglucose
glucoselevel
level
Blood
glucose
level
Blood
glucose
level
Blood
Blood
glucose
level
rises
to
normal
rises
to
normal
rises
to
normal
rises
to
normal
rises
to90
normal
(about
90
mg/100mL)
mL)
(about
mg/100
mL)
(about
90
mg/100
mL)
(about
90
mg/100
(about
90
mg/100
mL)
Blood glucose level
99 Blood glucose level
falls to
to normal
normal
falls
(about
90
mg/100 mL)
mL)
(about 90 mg/100
IfIf blood
blood
blood glucose
glucose
5555 If
If
blood glucose
glucose
continues
continues
to
to increase,
increase,
continues
to
continues
to increase,
increase,
hyperglycemia
inhibits
hyperglycemia
inhibits
hyperglycemia
inhibits
hyperglycemia
inhibits
release
of
GHRH
release of
of GHRH
GHRH
release
release of GHRH
10 If blood glucose
continues to decrease,
hypoglycemia inhibits
release of GHIH
44444
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Regulation and
Effects of hGH
and IGFs
High blood
blood glucose
glucose
66 High
(hyperglycemia)
(hyperglycemia)
stimulates release
release of
of
stimulates
2
• High levels of GH before puberty causes
Gigantism, after puberty causes Acromegaly.
Low levels of GH before puberty causes
Dwarfism, after puberty leads to some Metabolic
effects
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hGH disorders
3
Acromegaly
Gigantisim
Dwarfism or short stature
•
• Does not synthesize hormones
• Stores and releases hormones made by the
hypothalamus
• Transported along hypothalamohypophyseal
tract
• Oxytocin (OT) Peptide
• Antidiuretic hormone (ADH) or vasopressin
Peptide
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Posterior pituitary
(neurohyophysis)
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Hypothalamohypophyseal
tract
8
• synthesized in paraventricular nucleus of
hypothalamus
• During and after delivery of baby affects uterus
and breasts
• Enhances smooth muscle contraction in wall of
uterus
• Stimulates milk ejection from mammary glands
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Oxytocin (OT)
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• synthesized in supraoptic nucleus of
hypothalamus
• Decreases urine production by causing the
kidneys to return more water to the blood (
water reabsorption)
• Decreases water lost through sweating.
• Induces constriction of arterioles which
increases blood pressure (vasopressin)
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Antidiuretic Hormone (ADH)
10
•
•
•
•
Lack of ADH hormone or receptors causes Diabetes insipidus
Large volumes of urine
Dehydration and thirst
treatment: hormone replacement, salt restriction, antidiuretc
drugs
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Diseases of Post.Pituitary:
Diabetes insipidus
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1 High blood osmotic
5 Low blood osmotic
pressure inhibits
hypothalamic
osmoreceptors
pressure stimulates
hypothalamic
osmoreceptors
Osmoreceptors
2 Osmoreceptors
activate the
neurosecretory cells
that synthesize and
release ADH
receptors reduces or
stops ADH secretion
Hypothalamus
Nerve impulses
liberate ADH from
axon terminals in
the posterior
pituitary into
the bloodstream
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Osmoreceptors detect
high osmotic pressure
( increased solutes
3
concentration)
6 Inhibition of osmo-
ADH
Target tissues
4 Kidneys retain
more water,
which decreases
urine output
Sudoriferous
(sweat) glands
decrease water
loss by perspiration
from the skin
Arterioles constrict,
which increases
blood pressure
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Thyroid Gland
• Thyroxine or tetraiodothyronine (T4) (four iodine)
• Triiodothyronine (T3) (three iodine)
• Actions: Both increase BMR, stimulate protein
synthesis, increase use of glucose and fatty acids for
ATP production
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• Located inferior to larynx
• 2 lobes connected by isthmus
• Thyroid follicles ( follicular cells) produce thyroid hormones
• Parafollicular cells or C cells produce calcitonin
• Lowers blood Ca2+ by inhibiting bone resorption
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Thyroid gland
14
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Thyroid histology
15
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Thyroid Gland
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• Thyrotropin-releasing hormone (TRH) from
hypothalamus
• Thyroid-stimulating hormone (TSH) from anterior
pituitary
• Situations that increase ATP demand also increase
secretion of thyroid hormones (Pregnancy, cold,
high altitude, hypoglycemia)
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Control of thyroid hormone
secretion
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• Iodide (I-) actively transported into the follicle and
secreted into the colloid.
• Oxidized to iodine (Io).
• Iodine attached to tyrosine within thyroglobulin chain.
• Attachment of 1 iodine produces monoiodotyrosine (MIT).
• Attachment of 2 iodines produces diiodotyrosine (DIT).
• MIT and DIT or 2 DIT molecules coupled together.
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Synthesis of Thyroid Hormones
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Production of Thyroid Hormones
• T3 and T4 produced.
• TSH stimulates pinocytosis into the follicular cell.
• Enzymes hydrolyze T3 and T4 from thyroglobulin.
Attached to TBG and released into blood.
80% of T4 is converted into T3
T3 is 10-fold more powerful than T4
T4 plays a role in brain development
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•
•
•
•
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1. Iodide trapping (I-) by active
transport into follicular cells.
2. Synthesis of
(Thyroglobulin)TGB: then
exocytosis of TGB vesicles
3. Oxidation of iodide to iodine
(I2) and enter the lumen of
follicle.
4. Iodination of Tyrosines of
TGB ( sticky colloid) to give
mono and diiodotyrosine
5. Coupling of T1 and T2 (to
produce T3 and T4)
6. Pinocytosis and digestion of
colloid (Thyroglobulin) in
follicular cells
7. Secretion of thyroid hormone.
8. Transport in the blood via
thyroxine-binding globulins TBG
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Synthesis of thyroid hormones by the
thyroid gland
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1 Low blood levels of T3
and T43 or low metabolic
rate stimulate release of
Hypothalamus
TRH
2 TRH, carried
by hypophyseal
portal veins to
anterior pituitary,
stimulates
release of TSH
by thyrotrophs
5 Elevated
TSH
3 TSH released into
blood stimulates
thyroid follicular cells
Anterior
pituitary
4 T3 and T4
Thyroid
follicle
released into
blood by
follicular cells
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T3inhibits
release of
TRH and
TSH
(negative
feedback)
Actions of Thyroid Hormones:
Increase basal metabolic rate
Stimulate synthesis of Na+/K+ ATPase
Increase body temperature (calorigenic effect)
Stimulate protein synthesis
Increase the use of glucose and fatty acids for ATP production
Stimulate lipolysis
Enhance some actions of catecholamines
Regulate development and growth of nervous tissue and bones
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Actions of Thyroid Hormones
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• Stimulates protein synthesis.
• Stimulates synthesis of Na+/K+ pumps which use up
cellular [ATP] which results in Increased metabolic heat.
• Increases basal metabolic rate. Stimulates increased
metabolism of glucose, fatty acids and other molecules to
produce ATP under basal conditions such as (awake, rest,
fasting).
• Enhances catecholamines actions because they increase βreceptors synthesis.
• Together with growth hormone and insulin , Thyroid
hormones induce body growth and especially during
infancy.
• Promotes maturation of nervous system during infancy. (T422
and T3)
• Congenital hypothyroidism:
At birth thyroid function should be monitored.
If not treated, mental and growth retardation
(Cretinism)
• Hypothyroidism at adulthood: causes
(Myxedema) . Edema, slow heart rate, weight
gain, cold, lethargy and muscular weakness,
less alert.
• Goiter( enlarged thyroid): can be due to:
• Iodine-deficiency
Abnormal growth of the thyroid gland due to
insufficient iodine, and inadequate amounts of
T4 and T3.
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Thyroid Gland Diseases
• Lack of negative feedback inhibition.
• Continuous stimulation of TSH, which
causes abnormal growth.
• Hyperthyroidism: Graves’ disease
An autoimmune disease that produces TSH like
antibodies. (exophthalmos: protrusion of eyes)
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Goiter
Graves
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• Secreted from the parafolllicular cells (c-Cells of the thyroid
gland).
• Decreases calcium ( and phosphorus)level in the plasma by
inhibiting osteoclastic activity and enhancing bone uptake of
calcium
• Miacalcin drug is extracted from salmon is calcitonin more
potent than human CT. Used to treat osteoporosis.
• CT is regulated by negative feedback
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Calcitonin (CT)
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• Embedded in lobes of thyroid gland
• Usually 4 : 2 superior and 2 inferior
(Left and right)
• Parathyroid hormone (PTH) or
parathormone is a major regulator of
calcium Ca+2, magnesium Mg+2, and
phosphate HPO4 -2 ions in the blood
• Blood calcium level directly controls
secretion of both calcitonin and PTH
via negative feedback
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Parathyroid Glands and
hormone
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• Increases number and activity of osteoclasts
• Elevates bone resorption that releases Ca+2 and HPO4 -2 in blood.
• In kidneys, it increases tubular reabsorption( into blood) of Ca+2
and Mg+2 but increases loss of HPO4 -2 . Net effect lower blood
HPO4 -2.
• In kidneys, it stimulates formation of calcitriol the active vitamin
D or D3 that increases absorption of Ca+2Mg+2, and HPO4 -2
from the GI tract.
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Actions of Parathyroid
Hormone
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Parathyroid Glands
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Calcium Homeostasis
1 High level of Ca2+ in blood
stimulates thyroid gland
parafollicular cells to
release more CT.
3 Low level of Ca2+ in blood
stimulates parathyroid
gland chief cells to release
more PTH.
5 PTH also stimulates
the kidneys to release
CALCITRIOL.
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6 CALCITRIOL stimulates
increased absorption of
Ca2+ from foods, which
increases blood Ca2+ level.
4 PARATHYROID HORMONE (PTH)
promotes release of Ca2+ from
bone extracellular matrix into
blood and slows loss of Ca2+
in urine, thus increasing blood
Ca2+ level.
2 CALCITONIN inhibits
osteoclasts, thus decreasing
blood Ca2+ level.
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