Topics to Review

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Topics to Review

• Homeostasis
• Cell membrane structure
• Cell membrane proteins
• Synthesis and Exocytosis of secreted proteins
• Transcription and Translation
• Transmembrane transport
• Membrane potential

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Cellular Communication
The bodys 100 trillion cells need to communicate
in a manner that is rapid and conveys a
tremendous amount of information and occurs by 2
types of physiological signals

• Chemicals
• molecules that are secreted from cells into the
  extracellular fluid

• Electrical
• changes in the membrane potential of a cell

• The cells that receive the chemical or electrical
  signal are called target cells

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Methods of Cellular Communication

• Gap junctions
• direct cytoplasmic transport of electrical (ions)
  and or chemical signals between adjacent cells

• Contact-dependent signals
• cell surface molecules on the cell membrane of
  one cell attach to cell surface molecules on the
  cell membrane of an adjacent cell

• Local communication
• chemical signals that are released into the
  extracellular fluid from one cell diffuses a
  short distance to regulate itself and or a
  neighboring cell (autocrine and paracrine)

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• Long distance communication

-chemical signals (hormones) transported via
the circulatory system (endocrine and
neuroendocrine)

• electrical signals (action potentials) carried
  along axons of nerve cells (nervous) which result
  in the secretion of neurotransmitters

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• Hormones are secreted from

• the glands of the endocrine system
• see figure

• some organs
• heart, kidneys, stomach, skin, liver, ovaries and
  testes

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Control of Hormone Secretion (Release)
The hypersecretion or hyposecretion of a hormone
from a gland leads to too high or inadequate
levels of circulating hormone leading to
pathological conditions

• Following a particular stimulus, the gland can
  increase or decrease the rate of secretion

• Circulating (blood) levels of hormones are not
  permitted to get too high because they are
  controlled by 2 separate negative feedback loops

-activity of the target returns variable to the
set point

• circulating hormones decrease further secretion
  from the gland of origin

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• endocrine cells have protein receptors to the
  hormones that they secrete and hormone secretion
  is decreased when these receptors are bound by a
  hormone (autocrine)

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Stimulus
hormone secretion inhibits additional secretion
variable returns to set point inhibits additional
secretion
Endocrine Gland or Organ
hormone
Target Cell
Changes its activity
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Stimuli that Alter Hormone Secretion

• Hormone secretion rates from glands can be
  altered in response to

• humeral stimuli
• changes in levels of substances in blood
• glucose, K, CO2, pH

• neural stimuli
• neurotransmitters exocytosed onto a gland by a
  neuron

• hormonal stimuli
• hormones secreted from one gland or organ will
  stimulate another gland or organ to secrete a
  hormone

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Neurotransmitter vs Hormonal Control

• The responses to neurotransmitters are
• very rapid
• action potentials travel at speeds up to 270 mph
• response occurs within 0.005 sec. after secretion

• very short lived (simple reflex)
• neurotransmitters are either rapidly hydrolyzed
  in the synaptic cleft or are endocytosed out of
  the synaptic cleft back into the neuron

• The responses to hormones are
• slow
• distribution by blood can take seconds to minutes
• Responses at target can take minutes to hours
  before it can be measured

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• long lasting
• hormones can stay in the blood for minutes to
  days continuously causing an effect on the target

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Nervous System vs Endocrine System Reflexes
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Signaling Chemicals

• The amount signaling chemicals that are released
  from cells reflects the amount of response
  required to maintain homeostasis

• The amount of chemical messenger released is
  directly proportional to the extent of a
  homeostatic imbalance

• The magnitude of the response of a target cell to
  a signaling chemical depends largely on the
  amount of chemical messenger that is at the
  target cell

• The greater the amount of chemical messenger at
  the target cell, the greater the response

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Signal Molecules

• Signaling chemicals that are released by cells
  are considered to be the first messengers because
  they are responsible for initiating a series of
  events that ultimately lead to a response

• 2 distinct groups based on their chemistry and
  how they behave when they reach their target cells

• Hydrophobic (non-polar) chemicals diffuse through
  the cell membrane and enter the cytoplasm of the
  target cell

• steroid hormones
• synthesized from cholesterol
• names end in the suffix -one or -ol

• Hydrophilic (polar) chemicals are unable to cross
  the cell membrane of the target cell and
  therefore affect the cell from its surface

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• peptide hormones (3 to over 200 amino acids)
• monoamines (amino acid derivatives)

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Hormone Synthesis Steroid Hormones

• synthesized from cholesterol in SER and diffuses
  out of the cell
• differ in functional groups attached to 4-ringed
  steroid backbone

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Hormone Synthesis Peptides

• synthesized in RER as a prohormone
• Golgi complex further modifies it into hormone
• secreted out of cell by exocytosis

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Receptor Proteins

• In order for a chemical signal that is secreted
  from a cell into the extracellular fluid to
  create a response in a target cell, the target
  cell must possess a receptor protein to which the
  signal chemical binds

• Receptor proteins are either located
• on the surface of the cell membrane for
  hydrophilic signaling chemicals
• in the cell for hydrophobic signaling chemicals

• A single cell may have between 500 and 100,000
  receptor proteins which allow it to respond to a
  variety of signaling chemicals

• If a cell does not have a receptor protein that
  recognizes a particular signaling chemical, the
  cell will have no response

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Down-Regulation of Receptor Proteins
-If the signaling chemical concentration is
abnormally high for a sustained period of time
creating too large of a response, the target cell
can bring the response back to normal by a
reduction of the receptors

• Down-regulation is partially responsible for drug
  tolerance, where the response of a given dose
  decreases despite constant exposure
• increasing doses are therefore required to elicit
  a constant response

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Up-Regulation of Receptor Proteins

• Up-regulation of protein receptors is the
  opposite whereby a decrease in the concentration
  of signaling chemical causes the target cell to
  increase the number of protein receptors to
  normalize the response

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Hormone Transport in Blood

• Peptides and monoamines mix easily with blood

• Steroid hormones must bind to hormone binding
  proteins in the blood

• the binding of a steroid hormone to the binding
  protein is reversible

-bound hormones are attached to a
binding protein and are moved through the
circulatory system

• once unbound, the hormone exits the circulatory
  system to affect the target cell

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Hormone Transport and Action on Target
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Hormone Transport and Action on Target
-Both classes of chemicals will change the
activity of a target cell by changing the
activity of proteins in a cell (recall proteins
perform EVERY cellular function)

• some proteins will be activated, some will be
  inactivated and some will be unaffected
• the response of a target cell is very specific

• Hydrophobic signaling molecules alter protein
  synthesis to increase or decrease the number of
  proteins in a target cell (slow response)

• Hydrophilic signaling molecules change the
  activity of proteins that are currently in a
  target cell (fast response)
• flipping a molecular switch ON or OFF

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Hydrophobic Signal Molecules

• Following the diffusion of these chemicals into
  the cytoplasm of a target cell they bind to a
  receptor protein located either in the cytoplasm
  or in the nucleus

• The binding of the signaling chemical to the
  protein receptor initiates changes in the rate of
  transcription of genes in the target cell

• This ultimately changes the number of proteins in
  the target cell thus altering its activity

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Mechanism of Steroid Hormone Action
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Hydrophilic Signal Molecules

• Since these chemicals are unable to pass through
  the cell membrane, the receptor proteins for
  these molecules are integral (transmembrane)
  proteins with 3 distinct regions

• an extracellular portion that binds to the
  signaling chemical

• an intracellular portion that instructs the
  target cell how to respond to the signaling
  chemical

-a membrane spanning portion that connects
the extracellular portion to the intracellular
portion
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Hydrophilic Signal Molecules

• Following the binding of the signaling chemical
  to the protein receptor, one of 2 events occur

• if the protein receptor is a channel, the
  signaling chemical either opens or closes it
  which alters the membrane potential of the target
  cell

• if the protein receptor is not a channel,
  information is transferred through the cell
  membrane of the target cell and then transformed
  into an intracellular response

• this process is referred to as signal
  transduction
• a transducer is a device that converts a signal
  from one form into another

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Signal Transduction

• A biological transducer converts the message of
  an extracellular signaling chemical into
  intracellular messages which triggers a response
  in a cell

• In biological systems the signal is not only
  transformed, but it is also amplified (made
  larger)

-These pathways rely on cell membrane receptor
proteins and the production of intracellular
second messenger molecules that translate the
signal from the first messenger (eg. hormone)
into cellular responses
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Signal Cascades

• When a signaling chemical binds to the membrane
  protein receptor, the receptor initiates a series
  of responses beginning at the receptor and moving
  into the cell

• The sequence of reactions begins with the
  conversion of an inactive molecule (A) into an
  active form

• Activated A converts an inactive molecule (B)
  into active B which converts inactive C into
  active C and so on until at the final step, an
  intracellular substrate is converted into a
  product

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G Proteins

• GTP binding proteins, located on the cytoplasmic
  face of the membrane, link membrane protein
  receptors either to ion channels or to membrane
  enzymes

• The binding of a signaling molecule to a membrane
  protein receptor activates a G protein which will
  either
• open an ion channel in the membrane
• stimulate or inhibit an amplifier enzyme

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Adenylyl cyclase and cyclic AMP (cAMP)
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Phospholipase C and IP3 and DAG and Ca2
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Amplifier Enzymes and Second Messengers
-Amplification enzymes synthesize second
messenger molecules during the process of signal
transduction

• Second messengers are intracellular molecules
  that provide a means to influence the internal
  functioning of a cell by signaling chemicals
  (hormones) that cannot enter the cell

• 2 key enzymes that synthesize 2nd messengers

• adenylyl cyclase catalyzes the conversion of ATP
  into the second messenger cyclic AMP (cAMP)

• phospholipase C catalyzes the conversion of a
  membrane phospholipid into 2 different 2nd
  messengers

• Diacylglycerol (DAG)
• Inositol triphosphate (IP3)
• in some signal cascades IP3 stimulates the
  release of calcium ions from the smooth ER into
  the cytoplasm acting as a third messenger

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Protein Kinases
-Second messenger molecules activate protein
kinases which transfer a phosphate group (PO3-)
from ATP to a protein in a process called
phosphorylation

• The phosphorylation of proteins sets off a series
  of intracellular events that lead to the ultimate
  cellular response (conversion of substrates into
  products)

-This response is dependent on the type of
protein kinase (over 100 different types
discovered) that is activated and the proteins
that is (are) phosphorylated

• metabolic enzymes
• transport proteins
• proteins that regulate gene transcription

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Hypothalamus and Pituitary

• The anatomically superior hypothalamus and the
  pituitary are located in the brain

• the hypothalamus controls the secretion of
  hormones from the pituitary gland which in turn
  controls the secretion of hormones from other
  glands including the thyroid gland, adrenal
  glands and the gonads (ovaries/testes)

-The hypothalamus is composed of neurons which
secrete hormones into the bloodstream

• The pituitary gland is divided into two halves

• Anterior (adenohypophysis) is composed of
  glandular (epithelial) tissue

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• Posterior (neurohypophysis) is composed of
  collection of axons and axon termini whose cell
  bodies and dendrites are located in the
  hypothalamus

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Hypothalamus and Pituitary (Hypophysis)
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Hypothalamic Control of the Anterior Pituitary

• The hypothalamus secretes releasing hormones
  which travel through a portal circulation and
  stimulate the secretion of anterior pituitary
  hormones

• Thyrotropic Releasing Hormone (TRH)
• secreted when body temperature decreases and
  stimulates the secretion of Thyroid stimulating
  hormone (TSH) which targets the thyroid gland

• Corticotropic Releasing Hormone (CRH)
• secreted in times of stress and stimulates the
  secretion of Adrenocorticotropic hormone (ACTH)
  which targets the adrenal glands

• Gonadotropic Releasing Hormone (GnRH)
• secreted when testosterone or estrogen levels are
  low and stimulates the secretion of Follicle
  stimulating hormone (FSH) Luteinizing hormone
  (LH) which targets the testes or ovaries

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Hypothalamus and Anterior Pituitary
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Control of Releasing and Stimulating Hormones

• Hormones secreted from the thyroid gland, adrenal
  glands and gonads create a response in their
  respective targets

• These hormones also target the hypothalamus,
  anterior pituitary and the gland of origin to
  INHIBIT additional secretion of the releasing
  hormone, stimulating hormone

• This ensures that the amount of hormone that is
  secreted from each gland is just enough to create
  an appropriate change in the body
• prevents hypersecretion

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Other Hormones of the Anterior Pituitary

• Growth hormone (GH)
• A peptide hormone that stimulates the liver to
  secrete a class of hormones called insulin like
  growth factors (IGFs)

-IGFs targets skeletal muscle, bone and cartilage
and stimulate protein synthesis (growth)

• IGFs also targets adipose tissue and stimulates
  lipolysis (fat breakdown) to encourage the body
  to use fats as an additional energy source for
  growth

• Prolactin
• stimulates milk production by the breasts

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Posterior Pituitary

• Secretes 2 neurohormones into circulation
  following stimulation of the hypothalamus

• Antidiuretic hormone (ADH) or Vasopressin
• secreted in response to
• a decrease in body water content
• decrease in blood pressure
• an increase in extracellular solute concentration

• targets the kidneys and causes a reduction in the
  volume of urine produced
• retains body H2O
• increases in blood pressure
• decreases extracellular solute concentration

• Hyposecretion results in diabetes insipidus
• very high urine volume that contains no glucose

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• Oxytocin
• stimulates the contraction of smooth muscle in
  the uterus and breasts during childbirth and
  nursing

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Hypothalamic Control of the Posterior Pituitary
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Thyroid Gland

• Largest pure endocrine gland
• Covers the anterior and lateral sides of trachea

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Thyroid Gland

• The thyroid gland consists of thousands of
  follicles are spheres bordered by follicular
  cells (simple cuboidal epithelium) filled with
  colloid secrete the thyroid hormones
• Parafollicular (C) cells are found between
  follicles secrete the hormone calcitonin

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Thyroid Hormones

• The thyroid hormones, T4 (thyroxine) and T3, are
  considered to be steroid-like hormones
• are nonpolar
• have intracellular receptors that influence gene
  transcription

-Made from 2 nonpolar amino acids of tyrosine
bound to either 4 or 3 atoms of iodine
-Increase the metabolic rate by accelerating the
rate of cell respiration which produces a
significant amount of heat energy

• Recall that the secretion is controlled by the
  hypothalamic and anterior pituitary hormones in
  response to a decrease in body temperature (BT)
• ?BT ? TRH ? TSH ? thyroid hormone

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Adrenal Glands

• The adrenal glands (toward kidney) are
  pyramid-shaped glands on top of each kidney are
  structurally and functionally two glands in one

• Adrenal cortex (outside)
• epithelial tissue organized in 3 layers (zona)

• Zona glomerulosa (superficial layer)
• Zona fasciculata (middle layer)
• Zona reticularis (deep layer)

• Adrenal medulla (center of gland)
• nervous tissue that is the hormonal branch of the
  sympathetic nervous system (fight/flight)

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Adrenal Glands
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Adrenal Cortex
-Secretes hormones called corticosteroids
-Different corticosteroids are produced in each
zona

• Zona glomerulosa
• mineralocorticoids (mainly aldosterone)
• control body levels of sodium and potassium

• Zona fasciculata
• glucocorticoids (mainly cortisol)
• control blood levels of substrates for metabolism
  (glucose, fatty acids and amino acids)

• Zona reticularis
• gonadocorticoids (mainly androgens (male sex
  steroid hormones))
• secreted at low levels in males and females and
  may attribute to the onset of puberty

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Aldosterone (mineralocorticoid)

• Is secreted in response to any of the following
  stimuli

• an increase in blood K levels
• a decrease in blood Na levels
• a decrease in blood pressure
• secretion of ACTH from the anterior pituitary

• The target of aldosterone is the kidney

• The kidneys respond to aldosterone by

• increasing K urination (which decreases blood K
  levels)

• decreasing Na urination (which increases blood
  Na levels)
• an increase in Na levels in the blood causes an
  increase in blood pressure

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Cortisol (glucocorticoid)

• Is secreted in response to long term stress
  (lasting days/weeks/months)
• LTS ? CRH ? ACTH ? cortisol

• Targets include
• Liver causing gluconeogenesis
• the enzymatic synthesis of glucose from
  non-carbohydrate molecules such as amino acids
  which is subsequently released of into the blood
  to be used by cells for the purpose of ATP
  synthesis

-Adipose causing lipolysis of triglycerides
into free fatty acids which are subsequently
released into the blood to be used by cells for
the purpose of ATP synthesis
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Adrenal Medulla

• A sympathetic condition (fight or flight)
  stimulates the sympathetic centers of the
  medulla oblongata which fires APs that propagate
  along sympathetic nerves that synapse with
  chromaffin cells (modified sympathetic neurons)
  of the adrenal medulla and secrete 2
  catecholamines into circulation

• epinephrine (epi) (adrenaline)
• norepinephrine (norepi) (noradrenaline)

• Epinephrine and norepinephrine bind to adrenergic
  receptors on targets including

• Liver stimulating the enzymatic hydrolysis of
  glycogen (glycogenolysis) into glucose in the
  liver which is subsequently released into the
  blood

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-Adipose stimulates lipolysis to ? blood
fatty acids

• Cardiovascular system which increases the heart
  rate, strength of the heart beat and blood
  pressure to send blood around the body more
  quickly

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Pineal Gland -posterior of third ventricle
-pinealocytes synthesize melatonin from
serotonin -secretion on diurnal cycle high at
night, low during daylight
Melatonin functions -play role in timing of
sexual maturation -antioxidant (free radical
protection) -sets circadian rhythms
Heart -some cells of atrial walls secrete Atrial
Natriuretic Peptides (ANP)in response to stretch
-ANP promotes Na and water loss at kidney,
inhibits release of renin, ADH, and aldosterone
to reduce BP and volume
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Thymus -located deep to sternum -cells produce
thymosins -promote development and maturation of
T lymphocytes and the immune response

• Gonads
• Testes (male)
• -Interstitial cells produce androgens in response
  to LH Testosterone (most common)
• -produces male secondary sex characteristics
• -promotes sperm production
• -maintains secretory glands

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B. Ovaries (female) -Follicle cells produce
estrogens in response to LH and FSH Estradiol
(most important) -produce female secondary sex
characteristics -support maturation of
oocytes -stimulate growth of uterine lining
-Surge in LH causes ovulation, follicle
reorganizes to form corpus luteum produces
estrogens and progestins Progesterone (most
important)-prepares uterus for embryo growth
-accelerates movement of oocyte/embryo to uterus
( the hormone of pregnancy)- produced in
ovaries -enlargement of mammary glands
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Hormones affecting the breasts
Progesterone - causes maturation of breasts
Prolactin - causes production of milk
(hypothalmus). When Progesterone levels drop,
suckling causes stimulation. High level of this
hormone decreases Libido.
Oxytocin (pituitary) aides in milk being
squeezed out of breasts (milk letdown).
Stimultaes muscle cell in seconds of
suckling. Emotional influences also increase
Oxytocin. A crying Baby may stimulate milk
letdown.
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Common Disorders of the endocrine system
1. Pituitary Gland
a. Diseases of Growth Hormone
-Excess (usually due to pituitary tumor)
-before epiphyseal closure gigantism-after
acromegaly excessive growth of hands, feet,
face, internal organs
-Deficiency pituitary dwarfism failure to thrive
2. Thyroid Gland

• Hypothyroidism lack of T3/T4
• Myxedema (adults) lack of iodine, causes low
  body temp, muscle weakness, slow reflexes,
  cognitive dysfunction and goiter swollen thyroid

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Gigantism

• Excessive growth hormone before the growth plates
  fuse.
• Good for basketball
• Bad for horse racing.

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Acromegaly

• To much GH usually after the growth plates have
  fused.
• Results in great wrestlers.

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Dwarfism

• Hyposecretion of GH
• May require GH replacement therapy

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Cretinism (infants) genetic defect, causes lack
of skeletal and nervous system development
b. Hyperthyroidism excessive T3/T4, causes high
metabolic rate, high heart rate, restlessness,
fatigue
c. Graves Disease autoimmune disorder, produce
antibodies that mimic TSH causing overproduction
of thyroid hormones
3. Adrenal Gland
a. Cushing s Syndrome excessive
corticosteriods (increase ACTH from pituitary
tumor), results in hyperglycemia, decrease
muscle and bone mass, hypertension,edema, poor
healing, chronic infections
b. Addisons Disease deficient in
corticosteriods, results in weight loss,
hypoglycemia, decrease Na increase K in
plasma,dehydration, hypotension
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Endemic goiter

• Goiter enlarged thyroid gland
• results from dietary iodine deficiency.
• Cant produce TH,
• no feedback to Pituitary ? TSH
• This causes hypertrophy of the thyroid gland.

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Toxic goiter (Graves disease)

• Antibodies mimic TSH causing ?d TH to be
  released,
• Excessive Thyroxin levels
• elevated metabolism
• heart rate
• weight loss
• nervousness
• exophthalmos (bulging eyes)
• ANS induced sweating.

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Cushing Disease
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Cushing Disease
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Addison's Disease

• Results from a hyposecretion of ACTH or an
  autoimmune disease that damages the adrenals.
• Results in decreased glucocorticoids and
  mineralocorticoid release.
• Results in hypotension and hypoglycemia
• Corticosteroid replacement therapy

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4. Pancreas
a. Diabetes mellitus too much glucose in blood
(hyperglycemia)
Type I failure to produce insulin Type II
insulin resistance, sometimes insulin deficiency
Cells do not utilize glucose, ketone bodies
produced, too many ketoacidosis
5. Age Related Changes -very little change in
most hormone levels -adverse effects due to
changes in target tissues prevent reception or
response to hormone -gonads decrease in size and
hormone production