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The Endocrine System
Overview Acts with the nervous system (NS)
Major effector of homeostatic systems
Influences metabolic activities using hormones Responses occur more slowly but last longer than NS
Endocrine glands Pituitary, thyroid, thymus, pancreas, parathyroid, gonads,
adrenal and pineal glands
Figure 16.1
Pineal glandHypothalamus
Pituitary gland
Parathyroid glands(on dorsal aspectof thyroid gland)Thymus
Thyroid gland
Adrenal glands
Pancreas
Ovary (female)
Testis (male)
Overview
Nervous System Endocrine System Nerve impulses Neurotransmitters Faster responses Brief effects Acts on specific target
Hormones Slower responses Longer effects Broader influence
Overview Extensive integration between endocrine and nervous
systems Due to neuroendocrine cells
Cells that respond directly to neurotransmitters by releasing hormones Found in many organs (lungs, adrenals) Found extensively in the hypothalamus and pituitary –
considered neuroendocrine organs
Hormones
Chemical substances secreted by cells Very long-distance chemical signals
Secreted directly into the bloodstream Travel in the blood or lymph
Most are amino-acid based or steroid molecules
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Hormones Two main classes
1. Amino acid-based hormones Amines, peptides, and proteins
2. Steroids Synthesized from cholesterol Gonadal and adrenocortical hormones
Copyright © 2010 Pearson Education, Inc.
(a) Humoral Stimulus (b) Neural Stimulus
Capillary (lowCa2+ in blood)
Parathyroidglands
Thyroid gland(posterior view)
PTH
Parathyroidglands
1 Capillary blood containslow concentration of Ca2+,which stimulates...
1 Preganglionic sympatheticfibers stimulate adrenalmedulla cells...
2 …secretion ofparathyroid hormone (PTH)by parathyroid glands*
2 …to secrete catecholamines (epinephrine andnorepinephrine)
Figure 16.4 Three types of endocrine gland stimuli.
Endocrine Gland Stimulation
• Humoral Stimulation• Changes in blood or other
bodily fluids
• Examples: solute
concentration, temperature
Copyright © 2010 Pearson Education, Inc.
(a) Humoral Stimulus (b) Neural Stimulus (c) Hormonal Stimulus
Capillary (lowCa2+ in blood)
Parathyroidglands
Thyroid gland(posterior view)
PTH
Parathyroidglands
CNS (spinal cord)
Medulla ofadrenalgland
Preganglionicsympatheticfibers
Capillary
1 Capillary blood containslow concentration of Ca2+,which stimulates...
1 Preganglionic sympatheticfibers stimulate adrenalmedulla cells...
1hormones that...
2the anteriorpituitary glandto secretehormones that…
2 …secretion ofparathyroid hormone (PTH)by parathyroid glands*
2 …to secrete catechola-mines (epinephrine andnorepinephrine)
3glands to secrete hormones
Endocrine Gland Stimulation
• Neural Stimulation• Hormone is released is
directly triggered by a neuron
• Rapid response
• Example: milk ejection reflex
Figure 16.4 Three types of endocrine gland stimuli. Copyright © 2010 Pearson Education, Inc.
(a) Humoral Stimulus (b) Neural Stimulus(c) Hormonal Stimulus
Capillary (lowCa2+ in blood)
Parathyroidglands
Thyroid gland(posterior view)
PTH
Parathyroidglands
CNS (spinal cord)
Medulla ofadrenalgland
Preganglionicsympatheticfibers
Capillary
Hypothalamus
Thyroidgland
Adrenalcortex
Gonad(Testis)
Pituitarygland
1 Capillary blood containslow concentration of Ca2+,which stimulates...
1 Preganglionic sympatheticfibers stimulate adrenalmedulla cells...
1 The hypothalamus secreteshormones that...
2 …stimulatethe anteriorpituitary glandto secretehormones that…
2 …secretion ofparathyroid hormone (PTH)by parathyroid glands*
2 …to secrete catechola-mines (epinephrine andnorepinephrine)
3 …stimulate other endocrineglands to secrete hormones
Figure 16.4 Three types of endocrine gland stimuli.
Endocrine Gland Stimulation
• Hormonal Stimulation• One hormone triggers the
release of another
• Example: thyroid-stimulating
hormone stimulates the
release of thyroid hormone
Target Cell Specificity
Target cell = a cell affected by a hormone A single hormone may have more than one type of target cell Specific receptors
Hormone effects are due to alteration of cell’s activity Effects vary
Target Cell Specificity
Target cell effects depend on three factors1. Blood levels of the hormone2. Relative number of receptors on or in the target cell3. Affinity of binding between receptor and hormone
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Target Cell Specificity
Hormones influence the number of their receptors Up-regulation
Target cells form more receptors in response to the hormone
Down-regulation Target cells lose receptors in response to the hormone
Target Cell Specificity
Hormone concentration depends onRate of synthesis and release Speed of inactivation
Mechanism of Action Slow acting Fatty acids or steroids Examples: estrogen,
testosterone, cortisol
Fast acting Proteins or peptides Examples: insulin, oxytocin,
leptin
Thought Questions What is the plasma membrane made of?
What class of hormones (steroids or amino acid based) should be able to cross it?
Slow Acting Hormones
Steroid hormone crosses lipid-based membrane
Enters nucleus
Interacts with DNA
Changes cell function by initiating gene transcription
Relatively long lasting effects Examples: testosterone and estrogen
Figure 16.3
mRNA
New protein
DNA
Hormoneresponseelements
Receptor-hormonecomplex
Receptorprotein
Cytoplasm
Nucleus
Extracellular fluid
Steroidhormone
The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor.
Plasmamembrane
1
2
3
4
5
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Figure 16.3
mRNA
New protein
DNA
Hormoneresponseelements
Receptor-hormonecomplex
Receptorprotein
Cytoplasm
Nucleus
Extracellular fluid
Steroidhormone
The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor.
The receptor-hormone complex entersthe nucleus.
Plasmamembrane
1
2
3
4
5
Figure 16.3
mRNA
New protein
DNA
Hormoneresponseelements
Receptor-hormonecomplex
Receptorprotein
Cytoplasm
Nucleus
Extracellular fluid
Steroidhormone
The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor.
The receptor-hormone complex entersthe nucleus.
The receptor- hormonecomplex binds a hormoneresponse element (aspecific DNA sequence).
Plasmamembrane
1
2
3
4
5
Figure 16.3
mRNA
New protein
DNA
Hormoneresponseelements
Receptor-hormonecomplex
Receptorprotein
Cytoplasm
Nucleus
Extracellular fluid
Steroidhormone
The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor.
The receptor-hormone complex entersthe nucleus.
The receptor- hormonecomplex binds a hormoneresponse element (aspecific DNA sequence).
Binding initiatestranscription of thegene to mRNA.
Plasmamembrane
1
2
3
4
5
Figure 16.3
mRNA
New protein
DNA
Hormoneresponseelements
Receptor-hormonecomplex
Receptorprotein
Cytoplasm
Nucleus
Extracellular fluid
Steroidhormone
The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor.
The receptor-hormone complex entersthe nucleus.
The receptor- hormonecomplex binds a hormoneresponse element (aspecific DNA sequence).
Binding initiatestranscription of thegene to mRNA.
The mRNA directsprotein synthesis.
Plasmamembrane
1
2
3
4
5
Fast Acting HormonesAmino acid-based hormone binds to a receptor protein
(hormone is first messenger)
Activates internal second messenger (cyclic-AMP)
Activates enzymes
Rapid change in cell function
Relatively short term effects May be greatly amplified Examples: glucagon and parathyroid hormone
Figure 16.2
Hormone (1st messenger)binds receptor.
Receptor
G protein (GS)
Adenylate cyclase
Triggers responses oftarget cell (activatesenzymes, stimulatescellular secretion,opens ion channel,etc.)
Hormones thatact via cAMPmechanisms:EpinephrineACTHFSHLH
Inactiveprotein kinase
Extracellular fluid
Cytoplasm
Activeproteinkinase
GDP
GlucagonPTHTSHCalcitonin
1
2 3 4
5
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Figure 16.2
Hormone (1st messenger)binds receptor.
Receptoractivates Gprotein (GS).
Receptor
G protein (GS)
Adenylate cyclase
Triggers responses oftarget cell (activatesenzymes, stimulatescellular secretion,opens ion channel,etc.)
Hormones thatact via cAMPmechanisms:EpinephrineACTHFSHLH
Inactiveprotein kinase
Extracellular fluid
Cytoplasm
Activeproteinkinase
GDP
GlucagonPTHTSHCalcitonin
1
2 3 4
5
Figure 16.2
Hormone (1st messenger)binds receptor.
Receptoractivates Gprotein (GS).
G proteinactivatesadenylatecyclase.
Receptor
G protein (GS)
Adenylate cyclase
Triggers responses oftarget cell (activatesenzymes, stimulatescellular secretion,opens ion channel,etc.)
Hormones thatact via cAMPmechanisms:EpinephrineACTHFSHLH
Inactiveprotein kinase
Extracellular fluid
Cytoplasm
Activeproteinkinase
GDP
GlucagonPTHTSHCalcitonin
1
2 3 4
5
Figure 16.2
Hormone (1st messenger)binds receptor.
Receptoractivates Gprotein (GS).
G proteinactivatesadenylatecyclase.
Adenylatecyclaseconverts ATPto cAMP (2ndmessenger).
Receptor
G protein (GS)
Adenylate cyclase
Triggers responses oftarget cell (activatesenzymes, stimulatescellular secretion,opens ion channel,etc.)
Hormones thatact via cAMPmechanisms:EpinephrineACTHFSHLH
Inactiveprotein kinase
Extracellular fluid
Cytoplasm
Activeproteinkinase
GDP
GlucagonPTHTSHCalcitonin
1
2 3 4
5
Figure 16.2
Hormone (1st messenger)binds receptor.
Receptoractivates Gprotein (GS).
G proteinactivatesadenylatecyclase.
cAMP acti-vates proteinkinases.
Adenylatecyclaseconverts ATPto cAMP (2ndmessenger).
Receptor
G protein (GS)
Adenylate cyclase
Triggers responses oftarget cell (activatesenzymes, stimulatescellular secretion,opens ion channel,etc.)
Hormones thatact via cAMPmechanisms:EpinephrineACTHFSHLH
Inactiveprotein kinase
Extracellular fluid
Cytoplasm
Activeproteinkinase
GDP
GlucagonPTHTSHCalcitonin
1
2 3 4
5
GPCR second messenger system
Cellular Hormones
Some cells outside the endocrine glands have endocrine capacity Intestine secretin and cholecystokinin Kidney erythropoietin
Pituitary Gland
2 lobes1. Anterior pituitary lobe (adenohypophysis)
Glandular tissue Releases hormones formed within pituitary
2. Posterior pituitary lobe (neurohypophysis) Glial-like supporting cells and nerve fibers Releases hormones formed within hypothalamus
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Figure 16.5b
Hypothalamus
Anterior lobeof pituitary
(releases hormones made within the
pituitary)
Posterior lobe of pituitary
(releases hormones made within the hypothalamus)
Anterior Pituitary Hormones• Growth hormone (GH)
• Thyroid stimulating hormone (TSH)
• Adrenocorticotropic hormone (ACTH)• Follicle stimulating hormone (FSH)
• Luteinizing hormone (LH)• Prolactin
• Melanocyte stimulating hormone (MSH)
Growth Hormone (GH) Stimulates most cells
Main targets = bone & skeletal muscle
Functions Promotes protein synthesis Encourages use of fats for fuel Breakdown of glycogen
Imbalances of Growth Hormone Hypersecretion
Gigantism Acromegaly
Hyposecretion Pituitary dwarfism Simmond’s disease
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Acromegaly
Heaviness of jaw Increased size of digits
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Acromegaly?
Copyright © 2010 Pearson Education, Inc.
Pituitary Dwarfism
Large head
Normal size torso
Short arms and legs
Twin boys
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Simmond’s Disease
Caused by atrophy or destruction
of anterior pituitary
Extreme, progressive emaciation,
loss of body hair, premature aging
• Underlying cause must be addressed
(usually a pituitary tumor)
• Hormone replacement therapy is
effective, may come with side
effects (complicated where infertility
is involved)
Figure 16.6
Growth hormone
Feedback Inhibits GHRH releaseStimulates GHIHreleaseInhibits GH synthesisand release
Anteriorpituitary
Liver andother tissues
Indirect actions(growth-promoting)
Direct actions(metabolic,anti-insulin)
Insulin-like growthfactors (IGFs)
ExtraskeletalSkeletal FatCarbohydratemetabolism
Increased cartilageformation and
skeletal growth
Increased proteinsynthesis, andcell growth and
proliferation
Increasedfat breakdown
and release
Increased bloodglucose and otheranti-insulin effects
EffectsEffects
Produce
Hypothalamussecretes growthhormone—releasinghormone (GHRH), andsomatostatin (GHIH)
Initial stimulus
Physiological response
Result
Increases, stimulates
Reduces, inhibits
Growth Hormone Treatment rHGH used to treat a number of conditions Most common: HGH deficiency in children Wasting caused by AIDS Turner Syndrome Chronic renal failure
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Growth Hormone in Sports
Use without a prescription is illegal Suspected high level of abuse in all sports Supposed benefits: lean body mass, increased muscle
mass, injury resistance Drawbacks: lower stamina,
fatigue, no increase in muscle strength despite increased mass, increased risk of diabetes, joint and muscle pain, hypertension, osteoporosis
Growth Hormone in Agriculture
rBGH has been legal to be injected into dairy cows in the US since 1993
Increases milk production by ~15% Nutritionally identical (almost) Increased incidence of mastitis Different hormonal profile
Thyroid-Stimulating Hormone (TSH)
Produced by the anterior pituitary Stimulates the normal development and secretory
activity of the thyroid Regulation of TSH release
Stimulated by hypothalamus (thyrotropin-releasing hormone) Inhibited by rising blood levels of thyroid hormones
Copyright © 2010 Pearson Education, Inc. Figure 16.7
Hypothalamus
Anterior pituitary
Thyroid gland
Thyroidhormones
TSH
TRH
Target cellsStimulates
Inhibits
Adrenocorticotropic Hormone (ACTH)
Secreted by the anterior pituitary Stimulates the adrenal cortex to release corticosteroids
Gonadotropins (FSH & LH)
Follicle-stimulating hormone (FSH) and luteinizing hormone (LH or ICSH)
Secreted by the anterior pituitary Regulate function of ovaries and testes
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Gonadotropins (FSH & LH) Regulation of gonadotropin release
Triggered by gonadotropin-releasing hormone (GnRH) Absent from the blood in
prepubertal boys and girls
Suppressed by gonadal hormones Estrogen Progesterone Testosterone
NegativeFeedback
NegativeFeedback
Prolactin Secreted by the anterior pituitary
Stimulates milk production Blood levels rise toward the end of pregnancy Suckling stimulates PRH release and promotes continued milk
production
Prolactin Contributes to spermatogenesis in men
Hypersecretion may suppress gonadal hormones Amenorrhea in females Infertility, impotence in men
Plays a role in neurogenesis, fetal lung development, and
immune tolerance of fetus Production rises with use of MDMA (ecstasy)
Melanocyte Stimulating Hormone
Stimulates melanocytes• Stimulates melanocytes = darkening of skin• May influence brain activity
• Appetite, arousal
Control of Anterior Pituitary HormonesPituitary-Hypothalamic Relationships
Hypophyseal portal system Capillary plexuses Hypophyseal portal veins
Allows hormones to be sent from the hypothalamus to the pituitary via the bloodstream without being diluted in general circulation
Figure 16.5b
1
2
3
When appropriatelystimulated, hypothalamic neurons secrete releasing and inhibiting hormones into the primary capillary plexus.
Hypothalamus
Hypothalamic neuroncell bodies
Hypophysealportal system
Superiorhypophyseal artery
(b) Relationship between the anterior pituitary and the hypothalamus
Anterior lobeof pituitaryTSH, FSH, LH, ACTH, GH, PRL, MSH
• Primary capillaryplexus
• Hypophysealportal veins
• Secondarycapillaryplexus
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Figure 16.5b
1
2
3
When appropriatelystimulated, hypothalamic neurons secrete releasing and inhibiting hormones into the primary capillary plexus.
Hypothalamic hormones travel through the portal veins to the anterior pituitary where they stimulate or inhibit release of hormones from the anterior pituitary.
Hypothalamus
Hypothalamic neuroncell bodies
Hypophysealportal system
Superiorhypophyseal artery
(b) Relationship between the anterior pituitary and the hypothalamus
Anterior lobeof pituitaryTSH, FSH, LH, ACTH, GH, PRL, MSH
• Primary capillaryplexus
• Hypophysealportal veins
• Secondarycapillaryplexus
Figure 16.5b
1
2
3
When appropriatelystimulated, hypothalamic neurons secrete releasing and inhibiting hormones into the primary capillary plexus.
Hypothalamic hormones travel through the portal veins to the anterior pituitary where they stimulate or inhibit release of hormones from the anterior pituitary.
Anterior pituitaryhormones are secreted into the secondary capillary plexus.
Hypothalamus
Hypothalamic neuroncell bodies
Hypophysealportal system
Superiorhypophyseal artery
(b) Relationship between the anterior pituitary and the hypothalamus
Anterior lobeof pituitaryTSH, FSH, LH, ACTH, GH, PRL, MSH
• Primary capillaryplexus
• Hypophysealportal veins
• Secondarycapillaryplexus
Releasing Factors
Releasing factors Growth Hormone Releasing Hormone Thyroid Hormone Releasing Hormone
Inhibiting factors Identified for prolactin and GH
Negative feedback
Posterior Pituitary
Contains axons of hypothalamic neurons
Hormones produced by hypothalamus
Stores antidiuretic hormone (ADH) and oxytocin Released in response to nerve impulses
Copyright © 2010 Pearson Education, Inc. Figure 16.5a
1
2
3
4
Hypothalamicneuronssynthesize oxytocin and ADH.Paraventricular
nucleus Supraopticnucleus Optic chiasma
Hypothalamus
Inferiorhypophyseal artery
OxytocinADH
Infundibulum (connecting stalk)Hypothalamic-hypophysealtract
Axon terminalsPosteriorlobe ofpituitary
Copyright © 2010 Pearson Education, Inc. Figure 16.5a
1
2
3
4
Hypothalamicneuronssynthesize oxytocin and ADH.
Oxytocin and ADH aretransported along the hypothalamic-hypophyseal tract to the posterior pituitary.
Paraventricularnucleus Supraopticnucleus Optic chiasma
Hypothalamus
Inferiorhypophyseal artery
OxytocinADH
Infundibulum (connecting stalk)Hypothalamic-hypophysealtract
Axon terminalsPosteriorlobe ofpituitary
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Copyright © 2010 Pearson Education, Inc. Figure 16.5a
1
2
3
4
Hypothalamicneuronssynthesize oxytocin and ADH.
Oxytocin and ADH aretransported along the hypothalamic-hypophyseal tract to the posterior pituitary.
Oxytocin and ADH arestored in axon terminals in the posterior pituitary.
Paraventricularnucleus Supraopticnucleus Optic chiasma
Hypothalamus
Inferiorhypophyseal artery
OxytocinADH
Infundibulum (connecting stalk)Hypothalamic-hypophysealtract
Axon terminalsPosteriorlobe ofpituitary
Copyright © 2010 Pearson Education, Inc. Figure 16.5a
1
2
3
4
Hypothalamicneuronssynthesize oxytocin and ADH.
Oxytocin and ADH aretransported along the hypothalamic-hypophyseal tract to the posterior pituitary.
Oxytocin and ADH arestored in axon terminals in the posterior pituitary.
Oxytocin and ADH are released into the blood when hypothalamic neurons fire.
Paraventricularnucleus Supraopticnucleus Optic chiasma
Hypothalamus
Inferiorhypophyseal artery
OxytocinADH
Infundibulum (connecting stalk)Hypothalamic-hypophysealtract
Axon terminalsPosteriorlobe ofpituitary
Oxytocin
Stimulates uterine contractions during childbirth Synthetic versions used to induce labor
Also triggers milk ejection
(“letdown” reflex) in lactating women Plays a role in sexual arousal and
orgasm in males and females
“Bonding” hormone
Antidiuretic Hormone (ADH) Hypothalamic osmoreceptors respond to changes in the
solute concentration of the blood…
Solute concentration is high
Osmoreceptors transmit impulses to hypothalamic neurons
ADH synthesized and released
Urine formation inhibited
or…
Antidiuretic Hormone (ADH) Hypothalamic osmoreceptors respond to changes in the
solute concentration of the blood…
Solute concentration is low
ADH inhibited
Increased urine production
Homeostatic Imbalances of ADH
Diabetes insipidus* = Low ADH Huge output of urine and intense thirst Treated with ADH administration
* Not the same as excessive thirst and urine output caused by diabetes
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Figure 16.1
Pineal glandHypothalamus
Pituitary gland
Parathyroid glands(on dorsal aspectof thyroid gland)Thymus
Thyroid gland
Adrenal glands
Pancreas
Ovary (female)
Testis (male)
Thyroid Gland
Saddle bag shaped gland Largest endocrine gland in the body 3 hormones
Thyroxine (T4) Triiodothyronine (T3) Calcitonin
Thyroid hormone
Figure 16.8
Site of T3, T4
synthesis
Site of calcitoninsynthesis
Thyroid Hormone (TH)
Actually two related compounds T4 (thyroxin) 2 tyrosine molecules + 4 bound iodine atoms 90% of what is produced Converted to T3 in target cell
T3 (triiodothyronine) 2 tyrosines + 3 bound iodine atoms 4X more active than T4
Thyroid Hormone (TH)1) Iodide enters body
2) Converted to iodine by thyroid gland in the colloid
3) Iodine binds to tyrosines (part of thyroglobulin) in the colloid4) Iodinated tyrosines and are endocytosed by follicular cells and
combined w/lysosomes
5) Enzymes cleave T3/T4 from thyroglobulin6) Thyroglobulin freed and recycled while T3/T4 diffuses into
blood7) T3/T4 bind to thyroxin-binding globulin in blood
8) At tissue receptors, T4 is converted to active T3 by enzymes(See video on instructor website)
Figure 16.9
To peripheral tissues
T3
T3
T3
T4
T4
Lysosome
Tyrosines (part of thyroglobulinmolecule)
T4
DIT (T2)Iodine
MIT (T1)
Thyro-globulincolloid
Iodide (I–)
RoughER
Capillary
Colloid
Colloid inlumen offollicle
Thyroid follicle cells
Thyroglobulin is synthesized anddischarged into the follicle lumen.
Golgiapparatus
1
2
3
4
5
6
7
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Figure 16.9
To peripheral tissues
T3
T3
T3
T4
T4
Lysosome
Tyrosines (part of thyroglobulinmolecule)
T4
DIT (T2)Iodine
MIT (T1)
Thyro-globulincolloid
Iodide (I–)
RoughER
Capillary
Colloid
Colloid inlumen offollicle
Thyroid follicle cells
Iodide (I–) is trapped(actively transported in).
Thyroglobulin is synthesized anddischarged into the follicle lumen.
Golgiapparatus
1
2
3
4
5
6
7
Figure 16.9
To peripheral tissues
T3
T3
T3
T4
T4
Lysosome
Tyrosines (part of thyroglobulinmolecule)
T4
DIT (T2)Iodine
MIT (T1)
Thyro-globulincolloid
Iodide (I–)
RoughER
Capillary
Colloid
Colloid inlumen offollicle
Thyroid follicle cells
Iodideis oxidizedto iodine.
Iodide (I–) is trapped(actively transported in).
Thyroglobulin is synthesized anddischarged into the follicle lumen.
Golgiapparatus
1
2
3
4
5
6
7
Figure 16.9
To peripheral tissues
T3
T3
T3
T4
T4
Lysosome
Tyrosines (part of thyroglobulinmolecule)
T4
DIT (T2)Iodine
MIT (T1)
Thyro-globulincolloid
Iodide (I–)
RoughER
Capillary
Colloid
Colloid inlumen offollicle
Thyroid follicle cells
Iodideis oxidizedto iodine.
Iodide (I–) is trapped(actively transported in).
Thyroglobulin is synthesized anddischarged into the follicle lumen.
Iodine is attached to tyrosinein colloid, forming DIT and MIT.
Golgiapparatus
1
2
3
4
5
6
7
Figure 16.9
To peripheral tissues
T3
T3
T3
T4
T4
Lysosome
Tyrosines (part of thyroglobulinmolecule)
T4
DIT (T2)Iodine
MIT (T1)
Thyro-globulincolloid
Iodide (I–)
RoughER
Capillary
Colloid
Colloid inlumen offollicle
Thyroid follicle cells
Iodinated tyrosines arelinked together to form T3
and T4.
Iodideis oxidizedto iodine.
Iodide (I–) is trapped(actively transported in).
Thyroglobulin is synthesized anddischarged into the follicle lumen.
Iodine is attached to tyrosinein colloid, forming DIT and MIT.
Golgiapparatus
1
2
3
4
5
6
7
Figure 16.9
To peripheral tissues
T3
T3
T3
T4
T4
Lysosome
Tyrosines (part of thyroglobulinmolecule)
T4
DIT (T2)Iodine
MIT (T1)
Thyro-globulincolloid
Iodide (I–)
RoughER
Capillary
Colloid
Colloid inlumen offollicle
Thyroid follicle cells
Iodinated tyrosines arelinked together to form T3
and T4.
Iodideis oxidizedto iodine.
Thyroglobulin colloid isendocytosed and combinedwith a lysosome.
Iodide (I–) is trapped(actively transported in).
Thyroglobulin is synthesized anddischarged into the follicle lumen.
Iodine is attached to tyrosinein colloid, forming DIT and MIT.
Golgiapparatus
1
2
3
4
5
6
7
Figure 16.9
To peripheral tissues
T3
T3
T3
T4
T4
Lysosome
Tyrosines (part of thyroglobulinmolecule)
T4
DIT (T2)Iodine
MIT (T1)
Thyro-globulincolloid
Iodide (I–)
RoughER
Capillary
Colloid
Colloid inlumen offollicle
Thyroid follicle cells
Iodinated tyrosines arelinked together to form T3
and T4.
Iodideis oxidizedto iodine.
Thyroglobulin colloid isendocytosed and combinedwith a lysosome.
Lysosomal enzymes cleaveT4 and T3 from thyroglobulincolloid and hormones diffuseinto bloodstream.
Iodide (I–) is trapped(actively transported in).
Thyroglobulin is synthesized anddischarged into the follicle lumen.
Iodine is attached to tyrosinein colloid, forming DIT and MIT.
Golgiapparatus
1
2
3
4
5
6
7
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Thyroid Hormone (TH)
Major metabolic hormone (catabolism) Regulates tissue growth and development Increases reactivity of mature nerve cells Regulates heart rate Regulates movement of gastrointestinal tract
Figure 16.7
Hypothalamus
Anterior pituitary
Thyroid gland
Thyroidhormones
TSH
TRH
Target cellsStimulates
Inhibits
Imbalances of Thyroid Hormone
Goiter Cretinism Myxedema Graves disease
Figure 16.10
Goiter• Enlargement of thyroid
• Due to inflammation or hyperplasia
• Caused most commonly by iodine deficiency• Can also be caused by Hashimoto’s disease, ingestion of
goitrogens• Associated with both hypo
and hyperthyroidism
Cretinism• Congenital hypothyroidism
• Usually caused by maternal iodine deficiency during pregnancy
• Severely stunted physical growth, developmental delay
Myxedema• Hypothyroidism in adults
• Lethargy, low body temperature, swollen face, leathery skin
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Graves Disease• Hyperthyroidism
• Often treated by destruction or removal of thyroid tissue
Calcitonin
Made in parafolicular cells Lowers serum calcium
Inhibits bone resorption Stimulates uptake by the bone matrix
Antagonist to parathyroid hormone (PTH) Regulated by Ca2+ concentration in the blood
Negative feedback mechanism Falling Ca2+ in the blood inhibits calcitonin release
Parathyroid Glands
4-8 tiny glands embedded in the posterior aspect of the thyroid Parathyroid hormone (PTH)
Most important hormone in Ca2+ homeostasis
Figure 16.11
(b)
Capillary
Chiefcells
(secreteparathyroidhormone)
Oxyphilcells
Pharynx(posterioraspect)
Thyroidgland
Parathyroidglands
Trachea
Esophagus
(a)
Parathyroid Hormone Functions
Stimulates osteoclasts to digest bone matrix Enhances reabsorption of Ca2+ by the kidneys Increases absorption of Ca2+ by intestinal mucosa
Parathyroid Hormone Negative feedback
Rising Ca2+ in the blood inhibits PTH release
Hyperparathyroidism causes severe osteoporosis
Normal bone Osteoporotic bone
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Parathyroid Hormone Negative feedback
Rising Ca2+ in the blood inhibits PTH release
Hyperparathyroidism causes severe osteoporosis
Figure 16.12
Intestine
Kidney
Bloodstream
Hypocalcemia (low blood Ca2+) stimulatesparathyroid glands to release PTH.
1
2
3
Bone
Ca2+ ions
PTH Molecules
Figure 16.12
Intestine
Kidney
Bloodstream
Hypocalcemia (low blood Ca2+) stimulatesparathyroid glands to release PTH.
1 PTH activatesosteoclasts: Ca2+
and PO43S released
into blood.2
3
Bone
Ca2+ ions
PTH Molecules
Figure 16.12
Intestine
Kidney
Bloodstream
Hypocalcemia (low blood Ca2+) stimulatesparathyroid glands to release PTH.
1 PTH activatesosteoclasts: Ca2+
and PO43S released
into blood.2 PTH increasesCa2+ reabsorption
in kidneytubules.
3
Bone
Ca2+ ions
PTH Molecules
Figure 16.12
Intestine
Kidney
Bloodstream
Hypocalcemia (low blood Ca2+) stimulatesparathyroid glands to release PTH.
1 PTH activatesosteoclasts: Ca2+
and PO43S released
into blood.2 PTH increasesCa2+ reabsorption
in kidneytubules.
3 PTH promoteskidney’s activation of vitamin D,which increases Ca2+ absorptionfrom food.
Bone
Ca2+ ions
PTH Molecules
Figure 16.12
Intestine
Kidney
Bloodstream
Hypocalcemia (low blood Ca2+) stimulatesparathyroid glands to release PTH.
Rising Ca2+ inblood inhibitsPTH release.
1 PTH activatesosteoclasts: Ca2+
and PO43S released
into blood.2 PTH increasesCa2+ reabsorption
in kidneytubules.
3 PTH promoteskidney’s activation of vitamin D,which increases Ca2+ absorptionfrom food.
Bone
Ca2+ ions
PTH Molecules
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Adrenal Glands
Paired, pyramid-shaped glands atop the kidneys Essentially two glands in oneAdrenal medulla Nervous tissue: part of the sympathetic nervous system NE and Epinephrine
Adrenal cortex Three layers of glandular tissue Synthesize and secrete steroid hormones
Figure 16.1
Pineal glandHypothalamusPituitary gland
Parathyroid glands(on dorsal aspectof thyroid gland)Thymus
Thyroid gland
Adrenal glands
Pancreas
Ovary (female)
Testis (male)
Adrenal Cortex
Three layers that produce corticosteroids Outer layer = mineralocorticoids (ex. aldosterone) Middle layer = glucocorticoids (ex. cortisol) Inner layer = sex hormones or gonadocorticoids (ex. androgens)
Figure 16.13a
• Cortex
Kidney
• Medulla
Adrenal gland
CapsuleZona
glomerulosa
Zonafasciculata
Zonareticularis
Adrenalmedulla
(a) Drawing of the histology of theadrenal cortex and a portion ofthe adrenal medulla
Med
ulla
Cor
tex
Mineralocorticoids
Regulate extracellular Na+ and K+
Na+: affects ECF volume, blood volume, blood pressure K+: sets resting membrane potential of cells
Aldosterone is most important Stimulates Na+ reabsorption (and water retention) by kidneys Stimulates K+ secretion Effect on blood pressure? Consequences of overproduction?
Figure 16.14
Primary regulators Other factors
Blood volumeand/or blood
pressure
Angiotensin II
Blood pressureand/or blood
volume
K+ in blood
DirectstimulatingeffectRenin
Initiatescascadethatproduces
Kidney
Hypo-thalamus
Heart
CRH
Anteriorpituitary
Zona glomerulosaof adrenal cortex
Enhancedsecretionof aldosterone
Targetskidney tubules
Absorption of Na+ andwater; increased K+ excretion
Blood volumeand/or blood pressure
Inhibitoryeffect
Stress
ACTH Atrial natriureticpeptide (ANP)
Secretion mainlycontrolled by
blood pressure andpotassium levels
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Figure 16.14
Primary regulators Other factors
Blood volumeand/or blood
pressure
Angiotensin II
Blood pressureand/or blood
volume
K+ in blood
DirectstimulatingeffectRenin
Initiatescascadethatproduces
Kidney
Hypo-thalamus
Heart
CRH
Anteriorpituitary
Zona glomerulosaof adrenal cortex
Enhancedsecretionof aldosterone
Targetskidney tubules
Absorption of Na+ andwater; increased K+ excretion
Blood volumeand/or blood pressure
Inhibitoryeffect
Stress
ACTH Atrial natriureticpeptide (ANP)
Secretion mainlycontrolled by
blood pressure andpotassium levels
HPA axis (more on this later)
Glucocorticoids Regulate carbohydrate metabolism Keep blood sugar levels relatively constant
Stimulates gluconeogenesis during fasting
Suppress inflammation ↑ Vasoconstriction ↓ Vessel permeability Stabilizing lysosomes
Imbalances of Glucocorticoids
Cushing’s diseaseOver-production of cortisolUsually due to pituitary adenomaWeight gain (“moon face,” stretch marks)High blood pressure Poor short-term memory Excess hair growth Poor immune system
Figure 16.15
Imbalances of Glucocorticoids
Addison’s disease Deficiency of glucocorticoids and mineralocorticoids Hyperpigmentation of skin and mucous membranes Weight loss Fatigue Lightheadedness Muscle weakness Fever Anxiety Vomiting and diarrhea
Imbalances of Glucocorticoids
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Gonadocorticoids (Sex Hormones) Most are androgens (male sex hormones)
Converted to testosterone in tissue cells or estrogens
Supplement hormones secreted by gonads May contribute to
Onset of puberty Secondary sex characteristics Sex drive
Adrenal Medulla - Catecholamines
Epinephrine Affects the metabolic rate of all cells Bronchial dilation Increased blood flow to skeletal muscles and heart
Norepinephrine Increased blood pressure Increased heart rate Increased stroke volume
Figure 16.16
Short-term stress More prolonged stress
Stress
Hypothalamus
CRH (corticotropin-releasing hormone)
Corticotroph cellsof anterior pituitary
To target in blood
Adrenal cortex(secretes steroidhormones)
GlucocorticoidsMineralocorticoids
ACTH
Catecholamines(epinephrine andnorepinephrine)
Short-term stress response1. Increased heart rate2. Increased blood pressure3. Liver converts glycogen to glucose and releases
glucose to blood4. Dilation of bronchioles5. Changes in blood flow patterns leading to decreased
digestive system activity and reduced urine output6. Increased metabolic rate
Long-term stress response1. Retention of sodium
and water by kidneys2. Increased blood volume
and blood pressure
1. Proteins and fats convertedto glucose or broken downfor energy
2. Increased blood glucose3. Suppression of immune
system
Adrenal medulla(secretes amino acid-based hormones)
Preganglionicsympatheticfibers
Spinal cord
Nerve impulses
HPA axis (more on this later; really, I
promise)
Imbalances in Adrenal Medulla
Adrenal medullary hormones not essential for life Pheochromocytoma
Neuroendocrine tumor of adrenal medulla Secretes high levels of catecholamines What symptoms do you think would present?
Imbalances in Adrenal Medulla
Adrenal medullary hormones not essential for life Pheochromocytoma
Neuroendocrine tumor of adrenal medulla Secretes high levels of catecholamines High BP and heart rate, palpitations Anxiety/panic attacks Headaches Excessive sweating High blood glucose
Pancreas
Long, flat gland near stomach Exocrine function
Produces enzyme rich juice for digestion
Endocrine function Pancreatic islets (islets of Langerhans) Alpha () cells = glucagon
Hyperglycemic hormone Beta () cells = insulin
Hypoglycemic hormone
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Figure 16.1
Pineal glandHypothalamusPituitary gland
Parathyroid glands(on dorsal aspectof thyroid gland)Thymus
Thyroid gland
Adrenal glands
Pancreas
Ovary (female)
Testis (male)
Exocrine Pancreas
Pancreatic juices excreted into pancreatic duct Enzymes for digestion
Trypsinogen, pancreatic lipase, amylase, nuclease, others
Bicarbonate for neutralizing stomach acid
Required for optimal enzyme activity
Joins common bile duct at ampulla of Vater Drains into duodenum Blocking the pancreatic duct may lead to pancreatitis
Most commonly due to gallstones
Common bile duct
Pancreatic duct
Ampulla of Vater
Exocrine PancreasEndocrine Pancreas - Glucagon
Major target is the liver Initiates breakdown of glycogen into glucose (glycogenolysis) Causes increase in blood glucose Opposite action of insulin
For severe diabetic hypoglycemia (seizures, unconsciousness)
Endocrine Pancreas - Insulin Effects
Lowers blood glucose levels Enhances membrane transport of glucose Inhibits glycogenolysis and gluconeogenesis
Figure 16.18
Liver
Liver
Tissue cells
Stimulates glucose uptake by cells
StimulatesglycogenformationPancreas
Pancreas
Insulin
Bloodglucosefalls tonormalrange.
Stimulatesglycogenbreakdown
Bloodglucoserises tonormalrange.
Glucagon
StimulusBlood
glucose level
StimulusBlood
glucose level
GlycogenGlucose
GlycogenGlucose
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Figure 16.18
Liver
Liver
Tissue cells
Stimulates glucose uptake by cells
StimulatesglycogenformationPancreas
Pancreas
Insulin
Bloodglucosefalls tonormalrange.
Stimulatesglycogenbreakdown
Bloodglucoserises tonormalrange.
Glucagon
StimulusBlood
glucose level
StimulusBlood
glucose level
GlycogenGlucose
GlycogenGlucose
Figure 16.18
Liver
Liver
Tissue cells
Stimulates glucose uptake by cells
StimulatesglycogenformationPancreas
Pancreas
Insulin
Bloodglucosefalls tonormalrange.
Stimulatesglycogenbreakdown
Bloodglucoserises tonormalrange.
Glucagon
StimulusBlood
glucose level
StimulusBlood
glucose level
GlycogenGlucose
GlycogenGlucose
Figure 16.18
Liver
Liver
Tissue cells
Stimulates glucose uptake by cells
StimulatesglycogenformationPancreas
Pancreas
Insulin
Bloodglucosefalls tonormalrange.
Stimulatesglycogenbreakdown
Bloodglucoserises tonormalrange.
Glucagon
StimulusBlood
glucose level
StimulusBlood
glucose level
GlycogenGlucose
GlycogenGlucose
Figure 16.18
Liver
Liver
Tissue cells
Stimulates glucose uptake by cells
StimulatesglycogenformationPancreas
Pancreas
Insulin
Bloodglucosefalls tonormalrange.
Stimulatesglycogenbreakdown
Bloodglucoserises tonormalrange.
Glucagon
StimulusBlood
glucose level
StimulusBlood
glucose level
GlycogenGlucose
GlycogenGlucose
Figure 16.18
Liver
Liver
Tissue cells
Stimulates glucose uptake by cells
StimulatesglycogenformationPancreas
Pancreas
Insulin
Bloodglucosefalls tonormalrange.
Stimulatesglycogenbreakdown
Bloodglucoserises tonormalrange.
Glucagon
StimulusBlood
glucose level
StimulusBlood
glucose level
GlycogenGlucose
GlycogenGlucose
Figure 16.18
Liver
Liver
Tissue cells
Stimulates glucose uptake by cells
StimulatesglycogenformationPancreas
Pancreas
Insulin
Bloodglucosefalls tonormalrange.
Stimulatesglycogenbreakdown
Bloodglucoserises tonormalrange.
Glucagon
StimulusBlood
glucose level
StimulusBlood
glucose level
GlycogenGlucose
GlycogenGlucose
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Figure 16.18
Liver
Liver
Tissue cells
Stimulates glucose uptake by cells
StimulatesglycogenformationPancreas
Pancreas
Insulin
Bloodglucosefalls tonormalrange.
Stimulatesglycogenbreakdown
Bloodglucoserises tonormalrange.
Glucagon
StimulusBlood
glucose level
StimulusBlood
glucose level
GlycogenGlucose
GlycogenGlucose
Figure 16.18
Liver
Liver
Tissue cells
Stimulates glucose uptake by cells
StimulatesglycogenformationPancreas
Pancreas
Insulin
Bloodglucosefalls tonormalrange.
Stimulatesglycogenbreakdown
Bloodglucoserises tonormalrange.
Glucagon
StimulusBlood
glucose level
StimulusBlood
glucose level
GlycogenGlucose
GlycogenGlucose
Figure 16.18
Liver
Liver
Tissue cells
Stimulates glucose uptake by cells
StimulatesglycogenformationPancreas
Pancreas
Insulin
Bloodglucosefalls tonormalrange.
Stimulatesglycogenbreakdown
Bloodglucoserises tonormalrange.
Glucagon
StimulusBlood
glucose level
StimulusBlood
glucose level
GlycogenGlucose
GlycogenGlucose
Figure 16.18
Liver
Liver
Tissue cells
Stimulates glucose uptake by cells
StimulatesglycogenformationPancreas
Pancreas
Insulin
Bloodglucosefalls tonormalrange.
Stimulatesglycogenbreakdown
Bloodglucoserises tonormalrange.
Glucagon
StimulusBlood
glucose level
StimulusBlood
glucose level
GlycogenGlucose
GlycogenGlucose
Figure 16.18
Liver
Liver
Tissue cells
Stimulates glucose uptake by cells
StimulatesglycogenformationPancreas
Pancreas
Insulin
Bloodglucosefalls tonormalrange.
Stimulatesglycogenbreakdown
Bloodglucoserises tonormalrange.
Glucagon
StimulusBlood
glucose level
StimulusBlood
glucose level
GlycogenGlucose
GlycogenGlucose
Figure 16.18
Liver
Liver
Tissue cells
Stimulates glucose uptake by cells
StimulatesglycogenformationPancreas
Pancreas
Insulin
Bloodglucosefalls tonormalrange.
Stimulatesglycogenbreakdown
Bloodglucoserises tonormalrange.
Glucagon
StimulusBlood
glucose level
StimulusBlood
glucose level
GlycogenGlucose
GlycogenGlucose
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Imbalances of Insulin
Diabetes mellitus (DM)Due to hyposecretion or hypoactivity of insulinGlucose comes through in the urine and takes water
with it Three cardinal signs of DM Polyuria = copious urine output Polydipsia = excessive thirst Polyphagia = excessive hunger and food consumption
Diabetes Mellitus Type I Type II Gestational
Insulin cont.
Other hormones affecting insulin levels Growth hormone (GH) raises blood glucose Adrenocorticotropic hormone (ACTH) increases
glucocorticoid production, which raises blood glucose Effect on insulin release?
Insulin cont.
Other hormones affecting insulin levels Growth hormone (GH) raises blood glucose Adrenocorticotropic hormone (ACTH) increases
glucocorticoid production, which raises blood glucose Stimulates insulin release
Minor Endocrine Glands
Thymus Pineal gland
Thymus
2 lobed organ high in chest Thymosins Small proteins Stimulate lymphocyte production
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Thymus
Hugely important in immune system developmentActive during fetal development and for first two
years after birthBlood-thymic barrier strongest blood barrier in the
body
Pineal Gland
Small gland hanging from the roof of the third ventricle Melatonin Timing of sexual maturation and puberty Photoperiod Physiological processes that show rhythmic variations
Body temperature, sleep, appetite
Not well understood in humans
Stress
Physical
Psychological Real
Perceived
Strong emotional reactionsIndividual reactions vary
HPA Axis
Hypothalamic-pituitary-adrenal axis Regulates many body processes
Digestion, mood, immune system, metabolism
Most significantly: body’s response to long-term stress
Figure 16.16
Short-term stress More prolonged stress
Stress
Hypothalamus
CRH (corticotropin-releasing hormone)
Corticotroph cellsof anterior pituitary
To target in blood
Adrenal cortex(secretes steroidhormones)
GlucocorticoidsMineralocorticoids
ACTH
Catecholamines(epinephrine andnorepinephrine)
Short-term stress response1. Increased heart rate2. Increased blood pressure3. Liver converts glycogen to glucose and releases
glucose to blood4. Dilation of bronchioles5. Changes in blood flow patterns leading to decreased
digestive system activity and reduced urine output6. Increased metabolic rate
Long-term stress response1. Retention of sodium
and water by kidneys2. Increased blood volume
and blood pressure
1. Proteins and fats convertedto glucose or broken downfor energy
2. Increased blood glucose3. Suppression of immune
system
Adrenal medulla(secretes amino acid-based hormones)
Preganglionicsympatheticfibers
Spinal cord
Nerve impulses
HPA axis (finally)
Stress
Short-term stress Sympathetic
Hypothalamus
Spinal cord
Adrenal medulla
EpinephrineNorepinephrine
“Sympathomimetic”
Long-term stress• Endocrine
Hypothalamus
Anterior pituitary
Adrenal Cortex
Glucocorticoids
(Cortisol)
Mineralcorticoids
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Copyright © 2010 Pearson Education, Inc.
Increased cortisol = negative feedback to hypothalamus
High cortisol baseline = reduced sensitivity to
negative feedback
Low cortisol baseline = increased sensitivity to
negative feedback
The Stress Response
Changes largely mediated by hypothalamus, with the effector being the adrenals
Three stages Alarm (acute, sympathetic) Resistance (chronic, endocrine) Exhaustion
Temporary change in homeostasis = General Adaptation Syndrome (GAS)
Alarm Reaction
Immediate Hypothalamus Sympathetic nervous system Adrenal medulla
Increased serum glucose Increased circulation
Resistance Reaction
Long-term modification Hypothalamus Pituitary gland
Many effects… Increases energy availability Produces new proteins Improves circulation
Figure 16.16
Short-term stress More prolonged stress
Stress
Hypothalamus
CRH (corticotropin-releasing hormone)
Corticotroph cellsof anterior pituitary
To target in blood
Adrenal cortex(secretes steroidhormones)
GlucocorticoidsMineralocorticoids
ACTH
Catecholamines(epinephrine andnorepinephrine)
Short-term stress response1. Increased heart rate2. Increased blood pressure3. Liver converts glycogen to glucose and releases
glucose to blood4. Dilation of bronchioles5. Changes in blood flow patterns leading to decreased
digestive system activity and reduced urine output6. Increased metabolic rate
Long-term stress response1. Retention of sodium
and water by kidneys2. Increased blood volume
and blood pressure
1. Proteins and fats convertedto glucose or broken downfor energy
2. Increased blood glucose3. Suppression of immune
system
Adrenal medulla(secretes amino acid-based hormones)
Preganglionicsympatheticfibers
Spinal cord
Nerve impulsesFight or Flight Resistance Exhaustion
Stressor too strong K+ loss = cell death Glucocorticoid depletion = cell starvation Immune system failure
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General Adaptation Syndrome (or Stress Response)
Video