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LECTURE #3 - (Feb 2, 2006:
PITCH
-differences in pitch are related to
differences in the width and stiffness of the basilar membrane (a membrane that
separates the cochlear duct from the tympanic duct) and sound waves of various
frequencies that cause specific regions of the basilar membrane to vibrate more
intensely than others
-high frequency or high pitched
sounds cause the basilar membrane to
vibrate near the base of the cochlea, near the oval window
-low-frequency or low-pitched sounds
cause the basilar membrane to vibrate
near the apex of the cochlea.
STATIC
EQUILIBRIUM
-Static
equilibrium is the maintenance of the position of the body (mainly the head)
relative to the force of gravity
-The
maculae of the vestibule are the
sense organs of static equilibrium
-The
macula contains the hair cells and
the otoliths, which are crystals of
calcium carbonate;
-When
the head is in an upright position, the otoliths sit on top of the hair cells
exerting a vertical pressure;
-When
the head is tilted to one side or the other, gravity shifts the position of the
otoliths to one side or another and, therefore, their pressure on the hair
cells varies accordingly.
DYNAMIC
EQUILIBRIUM
-Dynamic
Equilibrium is the maintenance of the body position (mainly the head) in
response to sudden movements,
such as rotation, acceleration, and deceleration,
-The
hair cells in the cristae of the
semicircular ducts are the primary sense organs of dynamic equilibrium
-When
the head rotates, the movement of the endolymph in the semi-circular canals
distorts the cilia in the hair cells, therefore, activating them
EQUILIBRIUM
PATHWAY
Depolarization (activation) of the hair cells within
the organs of equilibrium initiates nerve impulses in sensory neurons in
adjacent vestibular ganglia pass to the vestibulocochlear (cranial nerve #
VIII) nerve and reach the pair of vestibular nuclei located between the pons
and the medulla oblongata. The vestibular nuclei coordinate the information
arriving from both sides of the head and relay information to the cerebellum,
brain stem, spinal cord and to the cerebral cortex.
DISORDERS
ASSOCIATED WITH HEARING
1) Deafness is significant or total
hearing loss. The hair cells are easily damaged by continued exposure to
high-intensity sounds and may degenerate, producing deafness. Deafness is
classified as :
a)
sensorineural - caused by impairment
of the cochlear branch of the vestibulocochlear (VIII) nerve
b)
conduction - caused by impairment of the external and middle ear mechanisms
for transmitting sounds to the cochlea
-hearing aids are devices that translate sounds into electronic
signals that can be interpreted by the brain
-they take the place of hair cells,
which normally convert sound waves into electrical signals
-the implants are used for
individuals with sensorineural deafness,
i.e., deafness due to disease or injury that has destroyed hair cells of the
spiral organ
-electronic hearing aids consist of a microphone, an amplifier,
and a receiver. The microphone
transduces sound into an electrical signal and sends it to the amplifier. The
amplifier increases the amplitude of the electrical signal, and the signal may
be further modified by filters and volume or tone controls. The amplified
signal is transmitted to the receiver, where it is transduced into sound waves.
2) Meniere’s Syndrome - is a malfunction of the inner ear that may cause
deafness and loss of equilibrium. It results
from the accumulation of too much endolymph in the inner ear.
3) Vertigo - inappropriate sense of motion; abnormal conditions in the inner ear
send the endolymph into motion
4) Motion sickness - is a functional disorder precipitated by repetitive angular, linear,
or vertical motion and characterized primarily by nausea and vomiting
-preventive measures are more
effective than trying to treat symptoms once they have developed
5) Otitis media - is an acute infection of
the middle ear, primarily by bacteria
-it is characterized by pain, malaise, fever, and
reddening and outward bulging of the eardrum, which may rupture unless prompt
treatment is given. Children are more susceptible than adults are
MEDICAL
TESTS
1) Audiometry - to evaluate an
individual’s hearing acuity.
-a person is placed in a soundproof
room and listens through earphones to sounds produced by an instrument called
an audiometer while a technician (audiologist) notes whether or not the sounds
can be heard.
THE
ENDOCRINE SYSTEM
The endocrine system is responsible for long-term,
body-wide coordination and development of cellular function, which is most
dramatically seen in the transformation of morphology and behavior during
puberty.
ENDOCRINE
GLANDS
The
body contains two kinds of glands:
1)Exocrine
glands (sudoriferous, sebaceous, mucous and digestive) secrete their
products through ducts into body cavities or onto body surfaces (epithilia)
2)Endocrine
glands, by contrast, secrete their products (hormones) into the
extracellular spaces around the secretory cells, rather than into ducts. The
secretion then diffuses into capillaries and is carried away by the blood.
-paracrine: (side by side) w/ in tissue , cell communication. Local hormones= paracrine factors
-pheremones: effect different individuals of same species
-Examples: GLANDS (specialized cells) = pituitary,
thyroid, parathyroid, adrenal, and pineal gland.
ORGANS OF THE BODY which contain cells that secrete
hormones, but are not glands: 1.hypothalamus
2. pancreas 3. ovaries 4.testes, etc.
COMPARISON
OF NERVOUS AND ENDOCRINE SYSTEM
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Nervous System
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Endocrine system
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1) Together the nervous and
endocrine systems coordinate functions of all body systems:
-They
are interrelated - certain parts
of the nervous system stimulate or inhibit the release of hormones. Hormones,
in turn, may promote or inhibit the generation of nerve impulses.
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-the
nervous system controls homoeostasis through nerve impulses (action potentials) conducted along axons of
neurons
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the
endocrine system releases its messenger
molecules, called hormones, into the bloodstream. The circulating blood
then delivers hormones to virtually all cells throughout the body.
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2) The nervous system causes
muscles to contract and glands to secrete
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-the
endocrine system affects virtually all body tissues, altering metabolic
activities, regulating growth and development, and guiding reproductive
processes.
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3) Nerve impulses are
generally much more rapid in
producing their effects
-effects
of the nervous system are also quite brief
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Exact
opposite
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OVERVIEW OF
HORMONE EFFECTS
1) Hormones regulate the
internal environment, metabolism, and energy balance
2) They also help regulate
smooth and cardiac muscular contraction, glandular secretion, and certain
immune responses.
3) Hormones play a role in the
integration of growth and development, and in the maintenance of homeostasis
despite emergency environmental disruptions, and contribute to the basic
processes of reproduction.
HORMONES = messengers of the endocrine system
1) Hormones only affect
specific target cells that have specific
receptors to recognize a given
hormone (usually, it effects outside tissue of origin).
-effects depend on time, age gender.
Ie. Female estrogen up when menstruatingà Na retention
2) Receptors, like other
cellular proteins (not cells like in
sensations), are constantly synthesized and broken down.
down-regulation: hormone (or
neurotransmitter) is present in excess, the number of receptors may decrease thereby decreasing the responsiveness
of target cells to the hormone
up-regulation: hormone (or
neurotransmitter) is deficient, the number of receptors may increase),
making the target tissue more sensitive to the stimulating effect of the
hormone
- ie. Up reg, for insulin receptors
as a result of exercise.
- ie dn reg of insuline receptors
from inactivity
3) Hormone receptors can be blocked by synthetic hormone-like
compounds, preventing hormone action. For example, a compound developed in
France by Dr. Emile Bulieu (Sophia Loren's husband) RU486 (mifepristone) (abortifacient) is used as a contraceptive
because it binds to the progesterone
receptor. Progesterone is a
female hormone, necessary for the implantation
of the female ovum in the uterine wall. Therefore, by blocking the
effect of progesterone, the ovum cannot be implanted in the uterine walls.
CLASSIFICATION
OF HORMONES
1) Accordingly to the
relation between site of production and site of action:
a) hormones that pass into the blood to act on
distant target cells are called circulating
hormones or endocrines; they have a longer
life and are usually destroyed
in the liver, and excreted by
the kidney
b) hormones that act on target cells close to their
site of release are called local hormones (paracrines
or autocrines); they are quickly inactivated at the site of action.
2) Chemically:
a) biogenic amines - the simplest hormones, many derived from the
amino acid tyrosine. Ex. Thyroid hormones (T3 and T4); synthesized by
special pathways. Catecholamine (e,ne
dopamine)
b) proteins and peptides - containing chains of 3 to
200 amino acids, synthesized in rough ER.
Ex. TSH
c) steroids - are lipids derived from
cholesterol and synthesized in the smooth
endoplasmic reticulum. Ex. testosterone, estrogen(both overlap in function) aldosterone, estradiol most prominent
(sex hormones)
d) eicosanoids (including prostaglandins and leukotrienes)
- derived
from the fatty acid arachidonic acid. Ex. prostaglandins and
leukotrienes
e) nitric oxide
3) Solubility:
a) water soluble hormones circulate in free form in the blood; insulin
b)
lipid-soluble steroid and thyroid hormones are carried attached to transport proteins synthesized by the liver; estrogen
MECHANISMS OF HORMONE ACTION
1) The response to a hormone
depends on both the hormone and the target cell;
-various target cells respond
differently to the same hormone
2) Hormones bind to and
activate their specific receptors in
two quite different ways: through membrane
Lipid-soluble
hormones, including steroid hormones and thyroid hormones, affect cell
function by binding to and activating an intracellular
receptor (usually in the cytoplasm or nucleus), consequently altering gene
expression
-the hormone-receptor complex can move into
the nucleus and bind to "hormone-responsive
elements" on the DNA molecule, inducing the expression of a particular
gene or set of genes.
Water-soluble
hormones alter cell function by activating plasma membrane receptors, which initiate a cascade of events
inside the cell
- first messenger after a water-soluble hormone is released from an
endocrine gland, it circulates in the blood, reaches a target cell, and brings
a specific message to that cell; since such a hormone can deliver its message
only to the plasma membrane.
- second messenger is needed to relay the message inside the cell
where hormone-stimulated responses can take place;
-G-proteins are a common feature of most second messenger
systems; as integral membrane proteins, they are the intermediaries between
hormones (first messengers) and the second messengers.
-there are different types of second messengers:
a) the best known second messenger
is cyclic AMP (cAMP)
– adenosine monophosphate - synthesized from ATP by adenylate cyclase.
-G-proteins convey the signal to adenylate cyclase when the receptor is
occupied; they are the intermediaries between receptors and adenylate cyclase.
-cAMP does not directly produce a
particular physiological response, but instead activates one or more
enzymes known as protein kinases,
which then trigger a cascade of phosphorylation reactions which lead to
the activation of specific proteins (enzymes) or to gene expression, producing
a physiological response.
-the enzyme phosphodiesterase inactivates cAMP,
terminating the action of the hormone.
b) two other well known second
messengers are diacylglycerol (DAG)
and inositol triphosphate (IP3);
-they are
produced when G-proteins induce activation of an enzyme known as phospholipase C;
-phospholipase
C generates the two second messengers DAG and IP3 from membrane phospholipids
known as phosphatidylinositols
-IP3 induces release of Ca++
from intracellular stores
-DAG and the
intracellular Ca++ activate another kinase = protein kinase C
-this protein kinase C
triggers phosphorylation events that
may lead for example to the opening of Ca++ channels in the plasma membrane,
and activation of other enzymes.
CLINICAL APPLICATION -the symptoms of cholera
are a direct result of the cholera toxin
(produced by bacteria) on G-proteins in the intestinal lining. The G-protein
becomes permanently activated in the walls of the intestine, causing massive
losses of water, Na+ and Cl-. Dehydration can occur. Treatment involves ample
replacement of the fluids lost - drink allot of water.
3) The responsiveness of a
target cell to a hormone depends on the hormone’s concentration and the number of receptors.
-the manner in which hormones
interact with other hormones is also important;
-three hormonal interactions are:
the permissive effect, the action of the second hormone is essential for the function of the
first,
the synergistic effect - when the action of the two hormones together
has a greater effect than the sum of
each acting alone
the antagonistic effect - when the action of one hormone opposes the action of the second
CONTROL OF HORMONE SECRETIONS
1) Most hormones are released in
short bursts, with little or no
release between bursts.
-regulation of hormone secretion
normally maintains homeostasis and prevents overproduction or underproduction
of a particular hormone
-when these regulating mechanisms do
not operate properly, disorders result, many of which are discussed below.
2) Hormone secretion is
controlled by signals from the nervous system, by chemical changes in the
blood, or by other hormones.
3) Most often, negative feedback systems regulate
hormonal secretions. When too much of a hormone is produced, its synthesis or
release is turned off.
HYPOTHALAMUS AND PITUITARY GLAND
1) The hypothalamus (inferior to the two lobes of the thalamus) is the
major integrating link between the
nervous and endocrine systems
2) The hypothalamus and the
pituitary gland (hypophysis)
regulate virtually all aspects of growth,
development, metabolism, and homeostasis
3) The pituitary gland is
located in the sella turcica of the
sphenoid bone and is differentiated into the anterior pituitary (adenohypophysis or glandular portion),
the posterior pituitary (neurohypophysis
or nervous portion), and pars intermedia (avascular zone in between)
-it is connected to the hypothalamus
by a stalk known as the infundibulum =
funnel
A) ANTERIOR PITUITARY GLAND (adenohypophysis)
a)
Hormones of the adenohypophysis are controlled by releasing or inhibiting
hormones produced by the hypothalamus
b) The blood supply to the anterior pituitary originates from
the superior hypophyseal arteries. hypothalamo-hypophyseal portal vessels: carries
releasing and inhibiting hormones to the anterior pituitary
c) Negative feedback
systems decrease the secretory activity of corticotrophs, thyrotrophs, and
gonadotrophs when levels of their target gland hormones rise.
d) Cell types and hormone
production by the anterior pituitary gland:
GH or somatotropin - stimulates body growth
through somatomedins (=insulin-like
growth factor), which are similar to insulin but potently promote growth.
-They are produced in response to hGH in the liver,
muscle, bones and other tissues.
-They: -promote protein synthesis (anabolism), and
decreases protein breakdown (catabolism)
-enhance lipid
catabolism
-decrease glucose uptake
by other cells, so that more is available to be utilized by the neurons.
Because
of this they may cause hyperglycemia
= high blood glucose. Persistent hyperglycemia may in turn have a diabetogenic
effect, incapacitating the pancreatic cells of producing insulin, causing diabetes
mellitus
-hGH is controlled by GHIH
(growth hormone inhibiting hormone, or somatostatin)
and GHRH (growth hormone releasing hormone, or somatocrinin)
-other stimuli that induce hGH
release and synthesis: decrease fatty
acid and increase amino acids in
the blood;
-hGH is the most abundant
hormone of the pituitary gland
4)
-PIH (prolactin inhibiting hormone).
The sucking action of a nursing infant decreases secretion of PIH.
5)
CORTICOTROPHS secrete:
-adrenocorticotropic hormone (ACTH)
-ACTH is synthesized in the pituitary as a large
precursor molecule, known as POMC (pro-opio-melano-cortin). The molecule is
broken down into three different “compounds” - ACTH, MSH and beta-endorphin
(neuropeptide in CNS that acts as a painkiller.)
ACTH
b-MSH b-end.
 NH2-
-COOH
POMC
-melanocyte-stimulating hormone dopamine which inhibits its
release.
-its role in humans is not quite understood, but it may
cause darkening of the skin;
-its circulating levels are very low
- corticotrophs which are remnants of the pars intermedia bwt. 2 lobes of
pituitary gland
LECTURE #4 - Endocrinology 2 (February 7)
Posterior pituitary gland (neurohypophysis)
-the neural connection between the
hypothalamus and neurohypophysis is via the supra optico hypophyseal tract
-although the posterior pituitary (posterior lobe),
or neurohypophysis, does not synthesize
hormones, it does store and release two hormones:
1) Antidiuretic hormone (ADH),
produced by the supraoptic nucleus in the hypothalamus, stimulates water
reabsorption by the kidneys and arteriolar constriction. Another name for it is
vasopressin because it increases
blood pressure by constricting the arterioles.
-the effect of ADH is to decrease
urine volume and conserve body water
-ADH is controlled primarily by
osmotic pressure of the blood
-When the osmotic pressure is high, due to lower
than normal concentration of water in blood, OSMORECEPTORS in the hypothalamus are turned "on" to
prevent water loss from the blood
-ADH has
three main targets: the kidneys, the sudoriferous (sweat) glands, and smooth
muscle in the blood vessel walls,
-ADH secretion can be modified by other stimulus: pain, stress, trauma, anxiety,
nicotine, and morphine. All these stimulate
ADH secretion.
-alcohol inhibits ADH secretion, increasing urine output, which may cause
the dehydration responsible for
headache and thirst typical of a hangover.
-DIABETES INSIPIDUS OR di (disorder
associated with dysfunction of the posterior pituitary)
There
are two types of DI:
a) NEUROGENIC
b) NEPHROGENIC - caused by a
lack of kidney response to ADH;
-difficult to treat;
restriction of salt in the diet advised.
-Both DI forms cause excretion of large
amounts of dilute urine (more than 10-fold) and subsequent dehydration and
thirst. The increase goes from 1-2 liters/day to about 20 liters/day.
-Note:
diabetes mellitus is a disorder of
the pancreas due to insulin deficiency
2) Oxytocin (OT)
is produced by the paraventricular nucleus in the hypothalamus,
-it stimulates contraction of the uterus and
ejection (letdown) of milk from the breasts
-during labor and delivery, OT is released in large
quantities
-OT secretion is controlled by uterine distention
and nursing
-synthetic OT (Pitocin) is often given to induce
labor or to increase uterine tone and control hemorrhage just before giving
birth
THYROID
GLAND
1) The thyroid gland is
located just below the larynx and has right and left lateral lobes connected by the isthmus.
It is the only gland that stores its products in large quantities, about a
100 day supply.
2) Histologically, the thyroid consists of:
-thyroid follicles composed of follicular cells, which secrete the THYROID HORMONES thyroxine (T4)
and triiodothyronine (T3)
-parafollicular or C cells,
which secrete CALCITONIN that helps
control calcium homeostasis.
THYROID
HORMONES
1) Thyroid hormones are synthesized from iodine and tyrosine within a
large glycoprotein molecule called thyroglobulin (TGB) which has 5,000 amino
acids.
-Thyroid hormones are transported in the blood by
plasma proteins, mostly thyroid-binding globulin (TBG).
Note:
TGB = precursor for synthesis of thyroid
hormones; TBG= for transport of thyroid
hormones;
2) Thyroid hormone synthesis
·
Iodide trapping - The follicular cells trap
iodide ions (I-) by actively transporting it from the blood into the cytosol.
The concentration of iodide (I-) in the thyroid is about 20-40 times higher
that in the blood.
·
Synthesis of thyroglobulin
(TGB) - It
is synthesized by the follicular cells. It has more than 5,000 a.a. and more
than 100 of these are tyrosine that may become iodinated. TGB is synthesized in
the rough ER, modified in the Golgi and then packaged in secretory vesicles.
They undergo exocytosis and TGB is secreted into the follicular lumen where it
accumulates as colloid.
·
Oxidation of iodide - An enzyme known as thyroid peroxidase oxidizes (removal of
electrons) the ion iodide (I-) to active iodide (I+),
which can then bind to tyrosine
·
Iodination of tyrosine - When I+ is
formed it binds immediately to tyrosine in thyroglobulin, forming
monoiodotyrosine (T1) or diiodotyrosine T2 if a second I2
binds
·
Coupling of T1
and T2 - Two T2 molecules join to form T4 =
tetraiodothyronine or thyroxine);
one
T1 and one T2 join to form T3 -
triiodothyronine. T4 and T3 are stored in association
with Thyroglobulin within the colloid.
·
Endocytosis and digestion of
colloid -
Colloid re-enters the follicular cells where it is degraded by the lysosomes,
with liberation of T3 and T4.
·
Secretion of thyroid
hormones -
T3 and T4 are lipid soluble and diffuse through the
plasma membrane into the blood.
·
Transport in the blood - In the blood T3
and T4 combine with thyroid-binding
globulin (TBG) and transthyretin
to be transported. Only a small amount remains free and is able to diffuse into
peripheral tissues.
3) Thyroid
hormones regulate the rate of metabolism by stimulating cellular oxygen use to produce ATP. More energy is consumed
during this process, and because energy is measured in calories this is known as
the calorigenic effect.
Functions: regulates growth and
development and the functioning of the nervous system. Thyroid hormones
stimulate the growth of the nervous system. Deficiency in early childhood
results in poor development especially of the brain and reproductive organs.
Secretion: is controlled by the level of iodide in the
thyroid gland and by negative feedback systems involving both the hypothalamus
and the anterior pituitary
-TRH
(thyrotropin releasing hormone) and TSH (thyroid stimulating hormone) are
responsible for initiating thyroid gland activity
4) Disorders associated with
the Thyroid gland
a).
Test in early childhood required by some states. Cretinism can be.
b.
Can be treated by oral administration of thyroid hormones.
d) Goiter - enlarged thyroid
gland. in countries where the iodine intake is inadequate. Characterized
by low thyroid hormone, low TSH, and thyroid gland enlargement.
-chronic lack of iodine in diet
produces large underactive thyroid gland
-in US iodine is added to salt, so
goiter is rare.
e) Hamburger Thyrotoxicosis - Thyroid
hormones are orally active, which means that consumption of thyroid gland
tissue can cause thyrotoxicosis, a type of hyperthyroidism. Several outbreaks
of thyrotoxicosis have been attributed to a practice, now banned in the US,
called "gullet trimming", where meat in the neck region of
slaughtered animals is ground into hamburger. Because thyroid glands are
reddish in color and located in the neck, it's not unusual for gullet trimmers
to get thyroid glands into hamburger or sausage. People, and presumably pets,
that eat such hamburger can get dose of thyroid hormone sufficient to induce
disease. A report by Hedberg and colleagues (1987) on this topic is one of
several in the literature. They described an outbreak of thyrotoxicosis in
Minnesota and South Dakota that was traced to thyroid-contaminated hamburger. A
total of 121 cases were identified in nine counties, with the highest incidence
in the county having the offending slaughter plant. The patients complained of
sleeplessness, nervousness, headache, fatique, excessive sweating and weight
loss. (From: http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/hamburgers.html)
THYROID
FUNCTION TESTS
Basically
three types:
Radioiodine uptake – tests
the ability of the thyroid to trap and retain iodine. The patient ingests radioactive 123I or 131I
and sees how much accumulates in the thyroid
Serum concentrations of T4
or T3 – measures the total amount of thyroxine or triiodothyronine that circulate in the blood – blood
test
Thyroid ultrasound – to
evaluate the size, shape and overall structure of the thyroid
CALCITONIN
(another hormone produced by
the thyroid gland)
1) Calcitonin (CT) lowers the blood level of
calcium and phosphates by:
-inhibiting bone resorption
(breakdown of bone matrix) - decreases osteoclast activity
-
increasing calcium and phosphate uptake by bone matrix - increases osteoblast activity
-it
is produced in the parafollicular
cells.
-its
secretion is controlled by calcium
levels in the blood
-it
also controls levels of phosphates
-it
is not essential for maintenance of
calcium homeostasis.
PARATHYROID
GLANDS
1) Parathyroid glands are
embedded on the posterior surfaces of the lateral lobes of the thyroid
2) The parathyroids consist
of:
-principal (chief) cells which secrete parathyroid hormone (PTH) or parathormone
-oxyphil cells
of unknown function
3) Parathyroid hormone (PTH), or parathormone regulates the homeostasis of
calcium and phosphate by increasing blood calcium level and decreasing blood
phosphate level
Functions: a) increases the
number and activity of osteoclasts
(bone destroying cells), resulting in increased bone resorption = breakdown of
bone matrix. Calcium is stored in bone.
b) inhibits osteoblast
(bone producing cells) activity, resulting in a decrease in bone formation
c) acts on the kidneys to increase rate of removal of calcium (Ca2+) and magnesium (Mg2+)
from urine, returning them to the blood, so that less is excreted in urine
d) induces the synthesis and secretion of calcitriol in the kidneys, a hormone synthesized from vitamin D.
Calcitriol increases reabsorption of Ca2+, Mg2+, and
phosphate from the gasterointestinal tract into blood
Secretion is controlled by calcium
levels in the blood:
- high
calcium - secretion of calcitonin
from thyroid; low calcium, secretion
of PTH
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PTH
|
Calcitonin
|
|
|
Parathyroid
glands
|
Thyroid
Gland
|
Produced by
|
|
Increase
|
Decrease
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Effect on Osteoclasts (bone destruction)
|
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Decrease
|
Increase
|
Effect on Osteoblasts (bone formation)
|
|
Decrease
in calcium excretion (urine); Calcitriol
|
None
|
Effect on Kidneys
|
|
Low
blood calcium
|
High
blood calcium
|
Secretion Increased by
|
|
Increase
in blood calcium
|
Decrease
in blood calcium
|
Final Result
|
4) DISORDERS:
a) Tetany - results from a deficiency of calcium caused
by hypoparathyroidism. It is characterized by muscle twitches, spasms and
convulsions. Neurons and muscle fibers depolarize and produce spontaneous
action potentials.
b) Osteitis
fibrosa cystica is characterized by demineralized, weakened, and deformed bones,
resulting from the condition of hyperparathyroidism
LECTURE #4 - Endocrinology 2 (February 7)
Posterior pituitary gland (neurohypophysis)
-the neural connection between the
hypothalamus and neurohypophysis is via the supra optico hypophyseal tract
-although the posterior pituitary (posterior lobe),
or neurohypophysis, does not synthesize
hormones, it does store and release two hormones:
1) Antidiuretic hormone (ADH),
produced by the supraoptic nucleus in the hypothalamus, stimulates water
reabsorption by the kidneys and arteriolar constriction. Another name for it is
vasopressin because it increases
blood pressure by constricting the arterioles.
-the effect of ADH is to decrease
urine volume and conserve body water
-ADH is controlled primarily by
osmotic pressure of the blood
-When the osmotic pressure is high, due to lower
than normal concentration of water in blood, OSMORECEPTORS in the hypothalamus are turned "on" to
prevent water loss from the blood
-ADH has
three main targets: the kidneys, the sudoriferous (sweat) glands, and smooth
muscle in the blood vessel walls,
-ADH secretion can be modified by other stimulus: pain, stress, trauma, anxiety,
nicotine, and morphine. All these stimulate
ADH secretion.
-alcohol inhibits ADH secretion, increasing urine output, which may cause
the dehydration responsible for
headache and thirst typical of a hangover.
-DIABETES INSIPIDUS OR di (disorder
associated with dysfunction of the posterior pituitary)
There
are two types of DI:
a) NEUROGENIC - caused by hyposecretion
of ADH due to a brain tumor or brain trauma.
-treated by administration of ADH (injection or
nasal spray)
b) NEPHROGENIC - caused by a
lack of kidney response to ADH;
-difficult to treat;
restriction of salt in the diet advised.
-Both DI forms cause excretion of large
amounts of dilute urine (more than 10-fold) and subsequent dehydration and
thirst. The increase goes from 1-2 liters/day to about 20 liters/day.
-Note:
diabetes mellitus is a disorder of
the pancreas due to insulin deficiency
2) Oxytocin (OT)
is produced by the paraventricular nucleus in the hypothalamus,
-it stimulates contraction of the uterus and
ejection (letdown) of milk from the breasts
-during labor and delivery, OT is released in large
quantities
-OT secretion is controlled by uterine distention
and nursing
-synthetic OT (Pitocin) is often given to induce
labor or to increase uterine tone and control hemorrhage just before giving
birth
THYROID
GLAND
1) The thyroid gland is
located just below the larynx and has right and left lateral lobes connected by the isthmus.
It is the only gland that stores its products in large quantities, about a
100 day supply.
2) Histologically, the thyroid consists of:
-thyroid follicles composed of follicular cells, which secrete the THYROID HORMONES thyroxine (T4)
and triiodothyronine (T3)
-parafollicular or C cells,
which secrete CALCITONIN that helps
control calcium homeostasis.
THYROID
HORMONES
1) Thyroid hormones are synthesized from iodine and tyrosine within a
large glycoprotein molecule called thyroglobulin (TGB) which has 5,000 amino
acids.
-Thyroid hormones are transported in the blood by
plasma proteins, mostly thyroid-binding globulin (TBG).
Note:
TGB = precursor for synthesis of thyroid
hormones; TBG= for transport of thyroid
hormones;
2) Thyroid hormone synthesis
·
Iodide trapping - The follicular cells trap
iodide ions (I-) by actively transporting it from the blood into the cytosol.
The concentration of iodide (I-) in the thyroid is about 20-40 times higher
that in the blood.
·
Synthesis of thyroglobulin
(TGB) - It
is synthesized by the follicular cells. It has more than 5,000 a.a. and more
than 100 of these are tyrosine that may become iodinated. TGB is synthesized in
the rough ER, modified in the Golgi and then packaged in secretory vesicles.
They undergo exocytosis and TGB is secreted into the follicular lumen where it
accumulates as colloid.
·
Oxidation of iodide - An enzyme known as thyroid peroxidase oxidizes (removal of
electrons) the ion iodide (I-) to active iodide (I+),
which can then bind to tyrosine
·
Iodination of tyrosine - When I+ is
formed it binds immediately to tyrosine in thyroglobulin, forming
monoiodotyrosine (T1) or diiodotyrosine T2 if a second I2
binds
·
Coupling of T1
and T2 - Two T2 molecules join to form T4 =
tetraiodothyronine or thyroxine);
one
T1 and one T2 join to form T3 -
triiodothyronine. T4 and T3 are stored in association
with Thyroglobulin within the colloid.
·
Endocytosis and digestion of
colloid -
Colloid re-enters the follicular cells where it is degraded by the lysosomes,
with liberation of T3 and T4.
·
Secretion of thyroid
hormones -
T3 and T4 are lipid soluble and diffuse through the
plasma membrane into the blood.
·
Transport in the blood - In the blood T3
and T4 combine with thyroid-binding
globulin (TBG) and transthyretin
to be transported. Only a small amount remains free and is able to diffuse into
peripheral tissues.
3) Thyroid
hormones regulate the rate of metabolism by stimulating cellular oxygen use to produce ATP. More energy is consumed
during this process, and because energy is measured in calories this is known as
the calorigenic effect.
Functions: regulates growth and
development and the functioning of the nervous system. Thyroid hormones
stimulate the growth of the nervous system. Deficiency in early childhood
results in poor development especially of the brain and reproductive organs.
Secretion: is controlled by the level of iodide in the
thyroid gland and by negative feedback systems involving both the hypothalamus
and the anterior pituitary
-TRH
(thyrotropin releasing hormone) and TSH (thyroid stimulating hormone) are
responsible for initiating thyroid gland activity
4) Disorders associated with
the Thyroid gland
a)
Cretinism - b) Myxedema -
c)
Graves’ disease d)
Goiter - enlarged thyroid gland.
Popular in countries where the iodine intake is inadequate. Characterized
by low thyroid hormone, low TSH, and thyroid gland enlargement.
-chronic lack of iodine in diet
produces large underactive thyroid gland
e) Hamburger
Thyrotoxicosis - Thyroid hormones are orally active, which means that
consumption of thyroid gland tissue can cause thyrotoxicosis, a type of hyperthyroidism. Several
outbreaks of thyrotoxicosis have been attributed to a practice, now banned in
the US, called "gullet trimming", where meat in the neck region of
slaughtered animals is ground into hamburger. Because thyroid glands are
reddish in color and located in the neck, it's not unusual for gullet trimmers
to get thyroid glands into hamburger or sausage. People, and presumably pets,
that eat such hamburger can get dose of thyroid hormone sufficient to induce
disease. A report by Hedberg and colleagues (1987) on this topic is one of
several in the literature. They described an outbreak of thyrotoxicosis in Minnesota and South
Dakota that was traced to thyroid-contaminated
hamburger. A total of 121 cases were identified in nine counties, with the
highest incidence in the county having the offending slaughter plant. The patients complained of sleeplessness,
nervousness, headache, fatique, excessive sweating and weight loss. (From:
OID FUNCTION TESTS
Basically
three types:
Radioiodine uptake – tests
the ability of the thyroid to trap and retain iodine. The patient ingests radioactive 123I or 131I
and sees how much accumulates in the thyroid
Serum concentrations of T4
or T3 – measures the total amount of thyroxine or triiodothyronine that circulate in the blood – blood
test
Thyroid ultrasound – to
evaluate the size, shape and overall structure of the thyroid
CALCITONIN
(another hormone produced by
the thyroid gland)
1) Calcitonin (CT) lowers the blood level of
calcium and phosphates by:
-inhibiting bone resorption
(breakdown of bone matrix) - decreases osteoclast activity
-
increasing calcium and phosphate uptake by bone matrix - increases osteoblast
activity
-it
is produced in the parafollicular
cells.
-its
secretion is controlled by calcium
levels in the blood
-it
also controls levels of phosphates
-it
is not essential for maintenance of
calcium homeostasis.
PARATHYROID
GLANDS
1) Parathyroid glands are
embedded on the posterior surfaces of the lateral lobes of the thyroid
2) The parathyroids consist
of:
-principal (chief) cells which secrete parathyroid hormone (PTH) or parathormone
-oxyphil cells
of unknown function
3) Parathyroid hormone (PTH), or parathormone regulates the homeostasis of
calcium and phosphate by increasing blood calcium level and decreasing blood
phosphate level
Functions: a) increases the
number and activity of osteoclasts
(bone destroying cells), resulting in increased bone resorption = breakdown of
bone matrix. Calcium is stored in bone.
b) inhibits osteoblast
(bone producing cells) activity, resulting in a decrease in bone formation
c) acts on the kidneys to increase rate of removal of calcium (Ca2+) and magnesium (Mg2+)
from urine, returning them to the blood, so that less is excreted in urine
d) induces the synthesis and secretion of calcitriol in the kidneys, a hormone synthesized from vitamin D.
Calcitriol increases reabsorption of Ca2+, Mg2+, and
phosphate from the gasterointestinal tract into blood
Secretion is controlled by calcium
levels in the blood:
- high
calcium - secretion of calcitonin
from thyroid; low calcium, secretion
of PTH
|
PTH
|
Calcitonin
|
|
|
Parathyroid
glands
|
Thyroid
Gland
|
Produced by
|
|
Increase
|
Decrease
|
Effect on Osteoclasts (bone destruction)
|
|
Decrease
|
Increase
|
Effect on Osteoblasts (bone formation)
|
|
Decrease
in calcium excretion (urine); Calcitriol
|
None
|
Effect on Kidneys
|
|
Low
blood calcium
|
High
blood calcium
|
Secretion Increased by
|
|
Increase
in blood calcium
|
Decrease
in blood calcium
|
Final Result
|
4) DISORDERS:
a) Tetany - results from a deficiency of calcium
caused by hypoparathyroidism. It is
characterized by muscle twitches, spasms and convulsions. Neurons and muscle
fibers depolarize and produce spontaneous action potentials.
b) Osteitis
fibrosa cystica is characterized by demineralized, weakened, and deformed bones,
resulting from the condition of hyperparathyroidism
PTH
NECESSARY, CALCITONIN IS NOT
ADRENAL GLANDS
1) The adrenal glands are located
superior to the kidneys
-they consist of:
-an outer cortex (secretes steroids that are
essential for life) and
-an inner medulla (secretes catecholamines)
-covered by a connective tissue capsule.
ADRENAL
CORTEX
1) Histologically, the cortex is divided
into:
zona glomerulosa -
outer, secretes mineralocorticoids (mineral homeostasis)
zona fasciculata -
middle, widest, secretes glucocorticoids (glucose homeostasis)
zona reticularis -
inner, secretes gonadocorticoids, similar to androgens
2) Mineralocorticoids
such as aldosterone which accounts
for 95% of the mineralcorticoids produced
Functions: aldosterone increases sodium
and water reabsorption and decreases potassium reabsorption, helping to
regulate sodium and potassium levels in the body
Secretion: aldosterone secretion is
induced by dehydration, Na+ deficiency, K+ excess, and hemorrhage.
-aldosterone secretion is controlled by the renin-angiotensin pathway and the blood
levels of potassium
-In this pathway, renin contributes to the production of angiotensin II which has two targets:
-adrenal cortex, where it induces the
secretion of aldosterone
-smooth muscle in the walls of the
arterioles, where it causes vasoconstriction.
-we will discuss in more detail when
we cover the kidney; ( INCR. BP)
DISORDER related to aldosterone
hypersecretion: aldosteronism - tumor of
the zona glomerulosa. Causes increased Na+ and decreased K+
levels in blood. Muscular paralysis and hypertension may result if untreated.
3) Glucocorticoids
such as cortisol, which accounts for 95% of the glucocorticoids,
corticosterone and cortisone
Functions:-promote normal organic
metabolism, help resist stress, and serve as anti-inflammatory
substances
-increase the rate of protein catabolism (breakdown) mainly in
muscle fibers.
-increase gluconeogenesis - formation of glucose from sources other than
glycogen
-stimulate lypolysis - breakdown of triglycerides
-promote resistance to stress - increase ATP, and raise blood pressure
-anti-inflamatory effects: inhibit
activation of cells that participate in inflamatory responses such as mast
cells. Reduce levels of histamines and depress phagocytosys.
-they are useful for the treatment of chronic
inflamatory diseases such as rheumatoid arthritis & asthma
Secretion is controlled by CRH (corticotropin releasing hormone) from the
hypothalamus and ACTH (adrenocorticotropic hormone) from the anterior pituitary
DISORDERS associated with
glucocorticoid secretion are:
Addison’s
disease -
primary adrenocortical insufficiency.
Cushing’s
syndrome -
4) Gonadocorticoids such as androgens (= male
sex hormones) secreted by the adrenal cortex usually have minimal effects.
These androgens may be converted to estrogens (= female sex hormones).
-excessive production occurs in congenital (= present at birth, not
hereditary) adrenal hyperplasia
(CAH) resulting in virilism
(masculinization). This disorder results in enlarged adrenal glands. Excessive
production of adrenal androgens.
-either virilism or gynecomastia (excessive growth of male mammary glands)
may also result from tumors of the adrenal gland (virilizing or feminizing
adenomas, respectively)
ADRENAL
MEDULLA
1) The adrenal medulla consists
of hormone-producing cells, called chromaffin
cells, which surround large blood-filled sinuses (blood vessels)
-they receive direct innervation
from preganglionic neurons of the sympathetic division of the ANS.
-they are sympathetic
post-ganglionic cells
2) Medullary secretions are epinephrine
(80%) and norepinephrine (NE),
which produce effects similar to sympathetic responses = sympathomimetic
-they are released under stress
conditions by direct innervation from the autonomic nervous system.
-like the glucocorticoids of the
adrenal cortex, these hormones help the body resist stress.
-however, unlike the cortical
hormones, the medullary hormones are not
essential for life
-tumors of the chromaffin cells,
called pheochromocytomas, cause
hypersecretion of epinephrine and norepinephrine
-since these hormones create the
same effects as sympathetic nervous system, hypersecretion puts the individual into a prolonged state of
fight-or-flight response, and ultimately causing generalized fatigue and
weakness
-treatment - removal of the tumor.
KIDNEY
HORMONES
1)-calcitriol – steroid hormone produced
by the kidney
-The skin synthesizes an inactive
form of vitamin D from precursor
molecules in the presence of sunlight
-the kidneys
convert the inactive form of vitamin D produced by the skin, into Calcitriol, the active form of vitamin
D
-calcitriol stimulates absorption of calcium and phosphates along the digestive tract
-calcitriol stimulates the production of bone cells
such as osteoprogenitor cells and osteoclasts
-Children in Northern European
countries, because of low sunlight exposure, often developed RICKETS = soft bones that bend easily.
In Russia,
children used to receive UV light treatment to prevent the development of this
disease;
-in the US vitamin D is routinely added to
milk
2)-erythropoietin = EPO– a peptide hormone released
from kidney in response to low oxygen levels in kidney tissues; low oxygen =
hypoxia
-it stimulates red blood cell production from bone
marrow
-improves oxygen delivery to tissues
-when oxygen levels reach normal levels, EPO
formation goes quickly down to zero
- to stimulate the production of red blood cells,
climbers are given DIAMOX (carbonic anhydrase inhibitor) several days ahead of
the trip; its response can take up to 4 days
3)-RENIN – released from the kidneys
under conditions of ischemia due to poor blood flow
-juxtaglomerular
cells in the kidneys secrete renin
-renin is
an enzyme that catalyzes the conversion of a plasma protein – angiotensinogen – into angiotensin I in the blood
-angiotensin I is converted to angiotensin II in the lung tissue by an enzyme known as ACE (angiotensin converting enzyme)
which:
a) elevates arterial blood
pressure by causing vasoconstriction
b) increases production of
aldosterone by the adrenal glands and ADH from the pituitary which cause Na+
and water retention
c) stimulates thirst
Renin (kidney)
ACE
(lung)
Angiotensinogen (plasma)
Angiotensin I
Angiotensin II
HEART HORMONE
The
atria of the heart produce atrial
natriuretic peptide (ANP), which helps to lower blood pressure;
-the endocrine cells are located in the walls of the
atria and respond to stretching of the walls of the atria when there is too
much blood in the atria
-ANP opposes
the effect of angiotensin II, by
lowering the blood pressure but its weak
|
Release Hormone
|
Trophs
cells
|
Primary Hormone
|
Affected Area
|
Secondary Hormone
|
Function
|
|
Thyroxine RH
|
Thyro-
T
|
TSH
|
Thyroid
|
T3, T4
|
Metabolism & cell respiration
|
|
Corticotrophin RH
|
Cortico
T
|
ACTH
|
Adrenal Cortex
|
Cortisole, Cortizone
|
|
|
MSH
|
Skin (amphibians)
|
|
Skin darkening
|
|
Gonadotropin RH
|
Gonado
T
|
LH
|
Gonads:
ovaries and testes
|
N/A
|
Sex steroids: m: testosterone F: androgen,
estrogen
|
|
FSH
|
Stimulates maturation of germ cell
|
|
Prolactin RH
|
LactoT
|
Prolactin
|
N/A
|
N/A
|
Synthesize milk
|
|
GH RH not from hyp
Othal
|
Somato-
T
|
GH
|
Long bone, skeletal muscles
|
|
Growth of those areas
|
adenohyp
NEUROHP
|
OXYTOCIN
|
MILK EJACULATION
|
Smooth muscle contraction
|
Uterine contractions
|
Increase BP esp sex
|
|
ADH
|
RETAINS H2O
|
|
|
|
|
Hormone
|
Hyposecretion (less)
|
Hypersecretion
|
Treatment
|
|
GH
|
Pituitary Dwarfism:
b4 pueberty and childlike behavior
|
Acromegaly:
after pueberty: lg. face and limbs
Gigantism: b4
pueberty, proportionate
|
PD: insert GH
|
|
Prolactin
|
|
impotent in males and absence of menstrual cycles in
females.
|
|
|
T3
|
Cretinism -
dwarfism and mental retardation - during fetal life or early infancy. Leads
to deficient development of brain and skeleton
|
|
prevent by giving oral thyroid hormone at an early age.
Affects 1 in 5,000 births
|
|
ADH
|
Neurogenic DI:
due to a brain tumor or brain trauma
|
|
administration of ADH
|
|
T4
|
Myxedema - during adult years.
Hallmark is an Edema-accumulation of interstitial fluids that make the facial
tissues look puffy. A person becomes lethargic, but not retarded because the
brain is already developed
|
Graves’ disease - a
continuous production of thyroid hormones. No negative feedback. hallmark is
an edema behind the eyes - exophthalmos,
which causes the eyes to protrude.
|
Oral intake of hormones.
thyroidectomy, radioactive iodine to destroy thyroid tissue or antithyroid
drugs that inhibit synthesis of thyroid hormones
|
Addisons:
Caused by hyposecretion of glucocorticoids and aldosterone. Results in mental
lethargy, anorexia, nausea and vomiting, weight loss and muscular weakness.
Potential cardiac arrest due to loss of aldosterone.
Cushing’s syndrome
- caused by hypersecretion, especially of cortisol and cortisone. Results in
the redistribution of fat. Patients have a rounded moon face and spindly arms
and legs, and a pendulus (hanging) abdomen. Wound healing is poor. They
experience mood swings, and may develop osteoporosis. May be caused by the administration of glucocorticoids
(prednisone) to a transplant recipient to prevent organ rejection, for
treatment of asthma, or for treatment of a chronic inflamatory disorder such as
Lupus (an autoimmune disease).
| 
