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Bio 2A03 – Intro Lecture
Physiology
Explains the physical and chemical factors for the origin and progression of life
Environmental Physiology
How physiological systems respond and adapt to changing enironments
Comparative Physiology
!iersity of how physiology wor"s in arious organisms
Medical Physiology or Pathophysiolgy
A#normal physiology as a result of disease
Hierarchal Organization of the body
$ells tissues %unctional units organs organ systems organism
Cells
Muscle Cells
o &peciali'ed for contraction for moement
o &u#types include s"eletal (lim#s and s"in)* cardiac (heart)* and smooth (#lood
essels)
Nerve Cellso +enerate and propagate electrical signals
Connective Tissue Cells
o ,roide physical support to other structures
Epithelial Cells
o %unction as #arriers often inoled in secretion and a#sorption
Tissues
$ollection of similar cells performing similar functions
Functional nits
&u#units of an organ
Organs
Intact structure composed of 2 or more tissues
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Organ systems
$ollection of organs that function together
Homeostasis
-he internal enironment is ery sta#le een when the external enironment changes
E!tracellular Fluid "ECF#
Is rapidly transported #y the circulation and mixes #etween #lood and tissues #y moing
across capillary walls
It #athes the tissues and creates the internal enironment of the #ody
Negative Feedbac$
.egulated aria#le changes (ex/ #ody temperature) and the change is detected and
regulatory system responds to oppose the change and #uffer the internal enironment
$omponents of a negatie feed#ac" loop include
%& &ensor
'& Integrating centre
(& Effector
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Thermoregulation and Negative Feedbac$
1) -he regulated aria#le changes (temperature) which is detected #y the sensors
(thermoreceptors)
2) -he thermoreceptors then signal the #rain (integrating centre) which signals different
effectors (#lood essels* sweat glands etc/)
3) -he effectors then cause compensatory responses to return the internal enironment #ac"
to the set point
Bio 2A03 – Lecture 1
Carbohydrates
• onosaccharides (glucose)
• !isaccharides (sucrose)
• ,olysaccharides (glycogen)
Nucleotides
!A genetic information
.A protein translation
A-,* A!,4 5 Energy transfer
)ipids
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-riglycerides glycerol 6 3 fatty acids
,hospholipids
o Hydropho#ic tail (2 fatty acid chains)
o Hydrophilic head (phosphate containing group)
&teroids
o Ex cholesterolo &tructure inoles 7 rings (3 hexagons 6 1 pentagon)
Eicosanoids
Proteins
Amino acid polymers
o ade up of a central car#on attached to an amino group* a car#oxyl group* and a
residual . group
,eptide #onds lin" amino acids to create polypeptides
o
8ia condensation reaction,rotein structure depends on its structure (primary* secondary* tertiary* 9uaternary)
Protein Function is Controlled by*
%# ,rotein amount
a& Is controlled #y protein synthesis and degradation
'# Allosteric odifiers
a& #ind non5coalently to regulatory sites on the protein
b& affect protein function #y changing its structure
(# $oalent modulation
a& ,hosphorylation #y "inases and dephosphorylation #y phosphatasesb& Affect protein function #y changing its structure
Metabolism
&um of all chemical reactions in the cell
Types of +eactions
Hydrolysis or condensation (AB 6 H2: A:H 6 HB)
,hosphorylation or dephosphorylation (A!, 6 ,i A-, 6 H2:)
:xidation or reduction (H2 2H6 6 2e5)
Principles of Chemical E,uilibrium and )a- of Mass .ction
!ictate the direction of reersi#le reactions and the eentual concentrations of reactants
and products
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Enzymes
En'ymes are protein catalysts that increase the rate of #iochemical reactions #y reducing
the actiation energy (usually a factor of 10; to 101
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Both the su#strate and the product can #ind to the actie site of the en'yme allowing the
reaction to proceed in reerse
+ates of Enzyme +eactions
.ates of en'yme reactions (8) depend on
$oncentration of su#strates =&> and products =,>o -he higher the concentration* the more en'yme5su#strate complexes can #e
formed and the rate of the reaction will increase
o
En'ymatic actiity
o -he rate at which the en'yme cataly'es the reaction (" cat)
En'yme concentrations =E>
o -he higher the concentration* the higher the rate
o 8max ? " cat=E>
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o
-he affinity of the en'yme for its su#strate
o -he higher the affinity* the lower the @ m
o 8max does not change when affinity changes
• -emperature* pH and other physical factors
.llosteric Modulation
.egulatory site of the en'yme is different from the actie site (the site at which the
su#strate #inds)
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In order to actiate or inactiate the en'yme actiity* a modulator needs to #ind to the
regulatory site
-his #ond changes the en'yme shape allowing its actie site to either #e actiated or
inactiated
Covalent modification
,hosphorylation or dephosphorylation affects the actiity of an en'yme
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Energy Metabolism
Encompasses the pathways needed to conert the energy in food to A-, to power cellular
functions
-wo processes inoled in A-, production and A-, homeostasis are
o &u#strate5leel phosphorylation occurs in the a#sence of :2
ex/ anaero#ic glycolysis
o :xidatie phosphorylation
!epends on the supply of :2
:ccurs in the mitochondria
,rimary mode of A-, production
/lucose O!idation
Inoles the #rea"down of glucose to produce energy
,rocesses include glycolysis lin"ing step @re#s cycle oxidatie phosphorylation
$omplete oxidation of glucose yields 37 A-, most of which come from oxidatie
phosphorylation
In the a#sence of oxygen* glycolysis is followed #y lactate production yielding only 2
A-,
/lycolysis and )in$ing step
Brea"s down glucose and produces 2 molecules of pyruate and occurs in the cytosol
,yruate enters the mitochondria where the lin"ing step conerts it to acetyl5coA
.esult is acetyl5coA for the @re#s cycle* A!H for oxidatie phosphorylation and A-,
0rebs Cycle "tricarbo!ylic acid cycle#
Acetyl5coA enters the @re#s cycle in the mitochondrial matrix
.esults in
o A-,
o .educing e9uialent (A!H and %A!H2) which enter oxidatie phosphorylation
o -hey are called reducing e9uialents #ecause they act as temporary electron
carriers
O!idative Phosphorylation
A!H and %A!H2 donate their electrons to electron acceptors in the E-$ and are
oxidi'ed to A!6 and %A!
Electrons moe through the E-$ until they reduce :2 and H2:
-he energy released during this process is used to pump protons out of the mitochondrial
matrix
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,rotons then moe #ac" into the matrix (down their concentration gradient) through the
A-, synthase to ma"e A-,
:xidatie phosphorylation can meta#oli'e car#ohydrates* lipids* and proteins to ma"e
A-,
o Healthy cells usually #rea" down car#s and fats #ut in times of staration or tissue
#rea"down* they meta#oli'e proteins
Bio 2A03 – Lecture 2
Membranes
Are selectie #arriers
-ransport proteins on the mem#ranes dictate moement in or out of the cells or organelles
em#rane proteins can also #e inoled in detecting chemical messengers at the cell
surface
-ransport across mem#ranes is ery important for maintaining intracellular and
extracellular homeostasis
Intracellular fluid mostly contains @ 6 while extracellular fluid mostly contains (a6)
Transport Mechanisms across Membranes
,assie -ransport
• !o not re9uire A-,
•
&imple diffusion through lipid #ilayer• $arrier5mediated diffusion through transmem#rane protein channels
Actie -ransport
• .e9uire A-, and transport proteins
• ,rimary actie transport
• &econdary actie transport
1imple 2iffusion
oement of molecules from one location to another due to random thermal motion
$oncentration gradient proides a chemical driing force for diffusion
o &olute moes from regions of high concentration to lower concentration
(downhillC) until uniformly distri#uted
%lux is the rate of solute moement per unit time
o olecules moe in all directions #ut the net flux ( ? flux 1 – flux 2) is in the
direction of lower concentration
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!iffusie e9uili#rium
o et flux is 0
o Dhen moement in one direction is e9ual to the moement in the opposite
direction
!iffusion is only good for shorter distances #ecause the rate of diffusion slows down with
increasing distance
o !iffusion times (t) are proportional to distance s9uared (x2)
et diffusion flux rate is proportional to the concentration difference #etween two
locations ($)
o -he higher the concentration gradient* the higher the flux rate
o et diffusion flux rate across a mem#rane is also proportional to mem#rane
permea#ility
o ,ermea#ility descri#es the ease of passage of a su#stance across a mem#rane
Fic$3s )a-
et diffusion flux rate across a mem#rane (%) #ased on chemical driing forces
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-he permea#ility constant (@ ,) is affected #y
o -emperature
as temperature increases* diffusion increases
o &olu#ility in lipid #ilayers (non5polar s/ polar)
:2* $:2* fatty acids and steroid hormones are non5polar and diffuse more
rapidly than chargedFpolar solutes
o &i'e and shape of the molecule
&maller molecules diffuse faster
Electrical 2riving Force
et diffusion flux rate of a charged solute (ion) across a mem#rane depends on the
internal and external electrical charges
-here is a mem#rane potential (oltage* 8m) across the cell mem#rane due to
maintenance of distinct ionic composition inside and outside cells
o -ypically 5;0 to 5100 m8 inside
o :utside is positie
agnitude of 8m and the alency (charge) of the ion dictates the electrical driing force
Electrical driing force of a positie ion increases with increasing 8m
Electrochemical driving force
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-he com#ined effect of chemical and electoral forces dictates the diffusion of ions across
the mem#rane
-he e9uili#rium potential (E" ) for an ion is the 8m at which the electrical and chemical
forces are e9ual
If the electrical driing force and the chemical driing forces are e9ual* then
electrochemical driing force is 0
Dhen 8m is not e9ual to the E" for a particular ion* there is a electrochemical driing
force tending to cause diffusion
Nernst E,uation
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-he e9uili#rium potential differs #etween ions* depending on
o An ions concentration inside and outside the cell
o Its alency (charge)
E" can #e calculated with the ernst e9uation
Carrier4Mediated 2iffusion "Facilitated 2iffusion#
:ccurs through protein channelFcarriers* often for su#stances with otherwise low
mem#rane permea#ility
$hannels are selectie for particular ion (#ased on si'e* charge* etc/) and can #e regulated
to openFclose
-he rate of facilitated diffusion is dictated #y the same factors as simple diffusion except
that the rate is satura#leo -he rate reaches its maximum when a channelGs maximum capacity is reached
Primary .ctive Transport
em#rane proteins that carry out primary actie transport must hydroly'e A-, directly to
harness energy* so they can transport ions against their electrochemical gradients
em#rane proteins inoled are called A-,ases andFor ion pumps
o Ex/ a6F@ 6 5A-,ase
,rimary actie transport must constantly counteract passie ion lea"s across mem#ranes
to maintain the distinct ionic composition in the intracellular and extracellular
enironments
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Lea" is regulated #y channels in a manner that differs #etween ions
Ion pumping is one of the most A-, demanding processes in the cells
• a6 from I$% fills in the #inding sites of the protein
• Dhen A-, is hydroly'ed to form A!,* the protein channel opens outwards releasing the
a6 ions into the E$%
• @6 ions from the E$% enter the #inding sites of the protein
• Dhen the phosphate is remoed from the protein* the channel opens inwards releasing the
@6 ions into the E$%
1econdary .ctive Transport
Is carried out #y proteins that do not themseles hydroly'e A-,* #ut it relies upon ionic
gradients esta#lished #y other A-,aseso
%or ex many transporters use =a6> gradient esta#lished #y a6F@65A-,ase toco transport other su#stances against their electrochemical gradient
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o
-ransporters inoled in secondary actie transport can #e co5transporters or counter5
transporters (a"a antiporters)
o
Osmosis
,assie diffusion of water across mem#ranes
em#ranes are permea#le to water due to its small si'e* een though it is a polar
molecule
Dater diffusion occurs down its concentration gradient
o Dater concentration depends on the osmolarity of the solution
o :smolarity total solute particle concentration
o -he higher the osmolarity* the lower the water concentration
:smosis occurs in the direction of higher omsolarity
1 mole of dissoled particles ? 1 osmolar solution
o Ex/ 1 of glucose in solution ? 1 osmole
o Ex/ 1 of a$l ? 2 osmoles #ecauses it ioni'es in solution to a6 and $l5
Tonicity
%unction of the concentration of non5permeating solutes (those una#le to cross the cell
mem#rane) outside relatie to inside of the cell
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:smosis relates to total solute concentration while tonicity relates to how a cell functions
in a concentration
Isotonic
o E9ual concentrations of non5permeating solute outside and inside the cell
o o change in cell olume
Hypertonic
o Higher concentration of non5permeating solute outside than inside the cell
o the cell shrin"s as water moes out
Hypotonic
o Lower concentration of non5permeating solute outside than inside the cell
o -he cell swells as water moes in
Dhen a cell containing non5permeating solute is placed in a solution of e9ual
concentration of permeating solute* the permeating solute will enter the cell* diffusing
down its concentration gradient #ut the non5permeating solute will not
o -his will create the osmotic driing force for water diffusion into the cell creating
a hypotonic solution
o
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Compartmentalized Membrane Transport
Is esicular transport (in an intracellular compartment) needed to transport
macromolecules across the plasma mem#rane
Endocytosis
o oement of molecules into the cell with the formation of endosomes
o ,hagocytosis (cell eating)
$ell extends mem#rane around particle to create a phagosome
o ,inocytosis (cell drin"ing)
,lasma mem#rane indents to form endosome around solutes
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Exocytosis
o oement of molecules out of the cell to the E$% using secretory esicles
Ex/ neurotransmitter release at synapses
Epithelial Transport
-ransport of materials across entire cell layers
-he epithelial cells hae 2 surfaceso Apical mem#rane faces external enironment (lumen)
o Basolateral mem#rane faces the internal enironment (interstitial fluid)
-ight unctions
o %orm a selectie #arrier that limits moement #etween cells
o &olutes cannot pass #etween the cells that are connected #y tight unctions
Epithelial 5on Transport
Example Epithelial transport of a6 ions and glucose
• a6 and glucose enter the cell #y a co5transporter across the apical mem#rane (secondarytransport)* powered #y the outward transport of a6 across the #asolateral mem#rane #y
the a6F@6 pump (primary actie transport)
• Buildup of intracellular glucose creates a driing force for its diffusion from the cell
through #asolateral channels
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Epithelial 6ater Transport
oement of water across an epithelial cell layer occurs #y osmosis and depends upon
the actie transport of solutes to create an osmotic gradient
Here* the pumps concentrate the non5permeating solutes in the interstitial fluid which
creates a gradient that allows water to diffuse across the epithelial cells down the osmotic
gradient
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Transcytosis
oement of macromolecules across an epithelial cell layer #y esicular transport
• It is a com#ination of endocytosis and exocytosis across a cell
Bio 2A03 – Lecture 3
5ntercellular Chemical Messengers
,erform cell to cell communication
Hormones
o &ecreted #y endocrine cells
o -hey reach target cells ia #lood
o -hey are slow acting #ecause #lood ta"es time to circulate
o
Although they hae a slow onset* they are longer lasting than neural signalso Eg/ Insulin* glucose
eurotransmitters
o &ecreted #y nere cells at synapse with target cell
o -hey are fast acting #ecause the secretory cells are ery close to target cells
o Eg/ Acetylcholine* adrenaline
AutocrineF,aracrine agents
o Local homeostatic response
o .each target cells #y diffusion
o Autocrine when the secretory and target cells are the same cell
o ,aracrine when the secretory and target cells are neigh#oring cells
o Eg/ itric oxide
1ignal Transduction Path-ays
!etect intercellular messengers and conert them into an intracellular response
-hey hae 7 features
o &pecificity
-he signal molecule fits in its receptors while other molecules do not
o Amplification
1 receptor #inding can lead to seeral million intracellular signals
o !esensiti'ationFAdaptation %eed#ac" can shut off the receptor
o Integration
-he intracellular signal can #e the result of integration of multiple receptor
inputs (i/e/ the oerall response is a com#ination of indiidual responses
from different receptors)
+eceptors
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-he num#er of receptors #ound dictates the magnitude of the cellGs response/ It is
controlled #yo essengerGs concentration
o um#er of receptors present
o .eceptorGs affinity for messenger
An increase in the num#er of receptors (.) increases the num#er #ound #y messenger o 8max increases #ut @m doesnGt change
o
An increase in the affinity for messengers can increase the num#er of #ound receptors at
the same messenger concentration
o @m decreases #ut 8max remains the same
o
5ntracellular +eceptors
Bind to lipophilic messengers (ex/ steroid hormones)
Act as transcription factors to alter gene transcription and the translation of a specific
protein
.eceptors can #e located in the cytosol or in the nucleus
Membrane4bound receptors
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Bind to lipopho#ic messengers
3 main types include channel lin"ed* en'yme lin"ed* and +5protein5lin"ed receptors
$hannel lin"ed
o $hannel acts as a receptor called ligand5gated channel
o .espond ery 9uic"ly to messenger #inding
o A change in the electrical properties of the ell can initiate the cellular response to
messenger #inding
o Ex/ messenger #inding opens ion channel
o
En'yme5lin"ed
o Ligand5#inding domain on extracellular surface and an en'yme actie site on the
intracellular surfaceo essenger #inding alters the actiity of the intracellular en'yme domain of the
receptor
o Eg/ -yrosine "inase receptors phosphorylate proteins to induce cellular responses
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o
+5protein5lin"ed
o essenger actiates mem#rane proteins called +5proteins that #egin a signaling
cascade
o &ome +5protein5lin"ed receptors regulate ion channels
-hese ion channels respond more slowly to messenger #inding* due to the
time re9uired for the 5su#unit to #e actiate and #ind to the ion channel
In this case* the channel itself does not act as the receptor
o :ther +5protein5lin"ed receptors regulate en'ymes that produce secondary
messengers (eg/ Adenylyl cyclase to produce cA,)
o +5proteins can #e stimulatory (+s) or inhi#itory (+i)
o
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Messengers
,rimary (first) essenger inter cellular chemical messengers that reach the cell surface
o Ex/ hormones
&econdary (second) messengers intracellular messengers produced #y the #inding of the
first messengerso -hey act as chemical relays from the plasma mem#rane to the #iochemical
machinery inside the cell
o Ex/ +5protein receptor regulating the phosphatidylunositol (,I,2) second
messenger system
o
1econd Messenger .mplification
&econd messenger systems can amplify the signal from the first messenger
• Ex/ +5protein receptor regulating cA, production #y adenylate cyclase
Bio 2A03 – Lecture 7
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Endocrine /lands
&ecrete hormones directly into E$%
:pposite to exocrine glands #ecause these secrete products to the outsideEndocrine system and nerous system hae oerlapping features
o Endocrine glands are often under nerous control
o &ome hormones are released from neurons (neurohormones) rather than endocrine
glandso any su#stances can act as hormones in the circulation or as neurotransmitters in
the #rain
o -he hypothalamus5pituitary complex is the neuro5endocrine interface
( Classes of Hormones
Amines
o !eried from amino acids tyrosine and tryptophan
,rotein and ,olypeptide Hormones
&teroid Hormones
o !eried from cholesterol
.mines
$atecholamines
o All are deried from tyrosine
o !opamine eurotransmitter and hypothalamic hormone that inhi#its prolactin
secretiono orepinephrine and epinephrine
are neurotransmitter and adrenomedullary hormones
&erotonin
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o eurotransmitter and hormone deried from tryptophan that is inoled in sleep*
suppressing stress responses* and mood
-hyroid hormones
o -hyroxine (-7) and triodo5thyronine (-3)
o Hormones deried from tyrosine that regulates meta#olic rate and growth
Catecholamine synthesis
All chatecholamines are deried from tyrosine
Each successie en'ymatic step conerts tyrosine to a different catecholamine
-he particular catecholamine secreted #y an endocrine organ depends on the presence
and actiity of appropriate en'ymes
Ex/ -yrosine L5dopa dopamine norepinephrine epinephrine
o -yrosine cannot ust ump straight to norepinephrine/ It needs to do it in
successie steps
o
Protein and Polypeptide hormones
+rowth Hormone
o Hormone released #y the anterior pituitary
Atrial natriuretic peptide
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o Hormone released #y the heart to regulate sodium rea#sorption #y the "idneys
-hey are synthesi'ed #y protelytic cleaage of a prehormone in the E.* and the resulting
prohormones are then further cleaed to hormones during pac"aging into esicles #y
+olgi apparatus
o Hormones and prohormones are released #y $a265initiated exocytosis
o
1teroid Hormones
all are deriaties of cholesterol
o the ring structure of cholesterol is presered so all steroid hormones are lipophilic
(canGt #e stored in esicles)
Are produced #y
o +onads
o ,lacenta (sex hormones)
o
Adrenal cortexineralocorticoids (aldosterone)
Inoled in ion #alance
+lucocorticoids (cortisol)
Inoled in glucose meta#olism and stress response
sex hormones (testosterone and estrogen)
Hydrophilic Hormones
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peptides* proteins and some amines
cannot diffuse across mem#ranes so they are secreted #y exocytosis and #ind to
cell surface receptors
Hydrophobic Hormones
steroids and some amines
can diffuse through mem#ranes and #ind to intracellular receptors #ut re9uire carrier
proteins for transport in the #lood
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Effects on Target Cells
!irect
o Actiate or inhi#it some function of the cell
Indirect
o ,ermissie effects
o Alter the sensitiity of the target cell to other hormones #y up or downregulating
their receptors
Controls on Hormone 1ecretion
Hormone secretion is controlled #y
eural controls
o !irect from the $& (hypothalamic hormones) or ia autonomic nerous system
Another hormone (trophic hormone)
o .elease of one hormone affects release of other hormones
$hanges in a homeostatically regulated aria#le
o Ex/ changes in #lood glucose leel cause release of insulin and glucagon
Hypothalamus4Pituitary Comple!
Located in the #rain
Hypothalamus
o Is composed of neural tissue
o Axons from hypothalamus terminate in the posterior pituitary where they release
neurohormones into the #lood
,osterior pituitaryo Is composed of neural tissue
o Also called neurohypophysis
Anterior ,ituitary
o Is composed of epithelial tissue
o Also called adenohypophysis
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o eurosecretory cells in the hypothalamus release trophic hormones into
hypothalamus5pituitary portal systemo -rophic hormones stimulate release of different hormones from the anterior
pituitary
Posterior Pituitary Hormones
:ctapeptides
o ,eptides composed of J amino acid
o &ynthesi'ed in soma of giant neurons of the hypothalamus transported down
axons stored in synaptic esicles in terminal "no#s at #lood essels in
posterior pituitary released when action potentials reach axon terminals
Antidiuretic Hormone (A!H)
o Ex/ 8asopressin
o .eleased from neurons from paraentricular nucleus of hypothalamus
o
.eleased in response to low #lood olume
low #lood pressure
high E$% osmotic pressure (detected #y hypothalamus osmoreceptors)
o promotes water retention at "idney and raises #lood pressure #y asoconstricting
systemic arterioles
:xytocin
o .eleased from neurons from supra5optic nucleus of hypothalamus
o .egulates reproductie functions such as
Kterine contractions
il" eection
Hypothalamic 4 .nterior Pituitary Hormones
-here are < different hypothalamic tropic hormones
o Dhen released* they are at ery high local concentrations
o -hey are released li"e neurotransmitters #y action potentials
o All are short polypeptides except dopamine
o ,rolactin .eleasing Hormone (,.H) stimulates prolactin release
o ,rolactin Inhi#iting Hormone (,IH)inhi#its prolactin release
o -hyrotropin .eleasing Hormone (-.H) stimulates -&H release
o $orticotropin .eleasing Hormone ($.H)
stimulates A$-H releaseo +rowth Hormone .eleasing Hormone (+H.H) stimulates +H release
o +rowth Hormone Inhi#iting Hormone (+HIH) inhi#its +H release
o +onadotropin .eleasing Hormone (+n.H) stimulates LH and %&H release
-here are at least anterior pituitary hormones that are released into general circulation
o ,rolactin (,L)
+eneral reproductie functions
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,romotes #reast deelopment and mil" production
&uppresses oulation during #reast5feeding
o -hyroid &timulating Hormone (-&H)
-hyroid growth
&timulates -3 and -7 hormone release
o Adrenocorticotrophic Hormone (A$-H) ,romotes glucocorticoid release from the adrenal cortex in response to
stress
o +rowth Hormone (+H)
,romotes I+%51 release to promote growth
Alters protein synthesis
Alters car#ohydrate and lipid meta#olism throughout #ody
o Luteini'ing Hormone (LH) and %ollicle &timulating Hormone (%&H)
&timulates sex hormone production
,romotes oulation and deelopment of reproductie tissue
/igantism and .cromegaly
,ituitary Adenomas
o A#normal growth of endocrine cells within the pituitary gland
o -umor cells that increase secretion of hormones are functional adenomas
30M of functional adenomas secrete growth hormone
Negative Feedbac$ )oops
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&hort loop
o :ccurs when anterior pituitary tropic hormone inhi#its the release of
hypothalamic tropic hormone
Long loop
o :ccurs when the target hormone inhi#its the release of a tropic hormone
Bio 2A03 – Lecture ;
.drenal Corte!
ineralocorticoid hormones
o .egulate ion homeostasis
o Ex/ aldoestrone
+lucocorticoid hormones
o .egulate the stress response and meta#olic homeostasis
o Ex/ cortisol
In response to stress* cortisol triggers energy meta#oli'ation
It stimulates production of gluconeogenesis* plasma glucose* lipolysis*
proteolysis
.drenal Medulla
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$ontains chromaffin cells that secrete catecholamines when the sympathetic nerous
system is actiated
7eta 7loc$ers
Are antagonists that #loc" the #eta receptors to which first messengers #indEx/ propanolol
Pancreas
&ecretes glucagon and insulin which regulate glucose homeostasis
+lucagon
o &ecreted #y alpha cells
o &timulates glucose release into the #lood in response to a fall in #lood glucose
concentration
Insulin
o &ecreted #y #eta cells
o ,romotes glucose upta"e from the #lood in response to a rise in #lood glucose
concentration
2iabetes
-ype 1 !ia#etes
o +lucose production fails
o $aused #y auto5immune destruction of #eta cells
o -arget cells are under5stimulated
-ype 2 !ia#eteso :ccurs when target cells cannot detect insulin (insulin resistance)
o &timulation #y insulin does not cause glucose upta"e
Hormone 5nteractions
Antagonism
o Hormones with opposing effects
o Ex/ insulin and glucose
o .esults in fine tuned regulation
o Effects in the same direction can #e additie or synergistic (e9ual to or greater
than the sum of indiidual effects)
,ermissie
o Hormones are re9uired to for another hormones to wor"
o Ex/ thyroid hormones are needed to synthesi'e epinephrine receptors in some
cells
Thyroid /land
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&ecretes -3 and -7 in response to -&H from the anterior pituitary
o .egulates meta#olic rate
&ecretes calcitonin
o .egulates #lood calcium leels
%ollicles in the thyroid gland contain thyroglo#ulin (the precursor to thyroid hormones)
Dhen -&H is released into the #lood from the pituitary* receptors on follicular cells are
stimulated and thyroid hormones are released
o -hey are permissie hormones
Parathyroid /land
&ecretes parathyroid hormone
o .egulates meta#olic rate
o &ecretes calcitonin
Pineal /land
Located in the #rain #ut is composed of epithelial tissue
.eceies signals from the $&
&ecretes melatonin which is important for esta#lishing circadian rhythms (sleep cycles)
/onads
&ecrete sex hormones
o ales androgens (testosterone and androstenedione)
o %emales Estrogens (estradiol and progesterone)
Placenta
&ecretes sex hormones in pregnant females
1econdary Endocrine Organs
Heart
• Atrial atriuretic ,eptide
o .esponds to heart stretch
o .egulates a6 rea#sorption #y the "idneys
Lier
• Insulin5li"e +rowth %actors (I+%)
o .eleased in response to growth hormone
o &timulates growth
@idney
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• Eryhtropoietin
o .eleased in response to a change in "idneyGs demand for oxygen
o $auses .B$ production
Bio 2A03 – Lecture
Types of Cells in the Nervous 1ystem
1tructure of a Typical Neuron
!endrites
o umerous small #ranches
o .E$EI8E incoming information from other neurons ia synapses
o +raded potentials occur here
$ell #ody (soma)
o $ontains nucleus and most organelleso eta#olic functions and synthesis of #iomolecules occur here
Axon hilloc"
o Axons originate here
o Are trigger 'ones where action potentials are initiated as a result of summation of
graded potentials
Axon
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o -hic" process that rapidly conducts outgoing information coded as action
potentialso .E$EI8E information
&ynapse
o Area where a presynaptic neuron ma"es a speciali'ed contact and communicates
with post synaptic neuron
-erminal
o ,resynaptic compartment that sends information to other neurons or effector cells
( 1tructural Classes of Neurons
Bipolar
o :ne axon and a dendrite originating from a cell #ody in the middle
,seudo5unipolar
o :ne peripheral axon and a central axon that loo" li"e they are continuous #ut
connect to a cell #ody in the middle
ultipolar
o Lots of dendrites proecting from the cell #ody
• &ignal always traels in one direction only
.!onal Transport
Axons range in length from 1mm to 1 m
Axons help transport su#stances produced in the cell #ody
!iffusion is too slow* so speciali'ed mechanisms that inole esicles (axonal transport)
are re9uired
Anterograde transport
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o %rom cell #ody to axon terminal
.etrograde transport
o %rom axon terminal to cell #ody
Organization of Nervous 1ystem
Afferent diision
o $onducts information from external and internal sensors to the $& for
integration
Efferent !iision
o $onducts information from the $& to effector organs
( Functional Classes of Neurons
Afferent eurons
o ,seudo5unipolar neurons with peripheral axon endings terminating in the
peripheral organ and central axon terminating in the $&
o &ensory receptors
&ense external enironment
Include somatosensory system (s"in* muscles* oints) and special senses
(hearing* smell* taste)o 8isceral .eceptors
&ense internal enironment
Eg/ Blood pressure (#aroreceptors)
Efferent eurons
o ultipolar neuron with cell #ody and dendrites in the $&
o Enters ,& as it traels to the effector organ
o Efferent motor neurons innerate s"eletal muscle
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o Efferent neurons of the autonomic nerous system innerate many organs and
tissues in the #ody
Interneurons
o NNM of all neurons in the #ody
o All are in the $&
o ,erform all the functions of the $& including ,rocessing sensory information from the afferent neurons
&ending command to effector neurons
Classes of /lial Cells "/lia#
+lial cells in $& :ligodendrocytes
+lial cells in ,& &chwann cells
%orm an insulating wrap of myelin around the axons of neurons
o yelin consists of concentric layers of plasma mem#ranes of either
:ligodendrocytes or &chwann cells
&u#stantially reduce the lea"age of ions across the mem#rane
o ,roides electrical insulation
Helps neurons transport action potentials more rapidly
% Oligodendrocyte % 1ch-ann Cell
%orm seeral myelin sheaths %orms one myelin sheath
yelinates sections of seeral axons yelinates one section of an axon
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Bio 2A03 – Lecture <
Membrane Potential
.esting mem#rane potential
o
mem#rane potential across the mem#rane when the cell is at rest (i/e/ not sendingor receiing signals)
o %or neurons* resting 8m 5
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o +etting more negatie than the resting potential
o If ,@ increases* 8m will moe towards 5N7 m8
!epolari'ation
o +etting less negatie than the resting potential
o If , a increases* 8m will moe towards 60 m8
.epolari'ationo Dhen 8m returns to the resting 8m (5
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-he resting 8m is dictated #y lea" channels
o -hey are always open unli"e gated channels
Types of /ated Channels
Ligand +atedo :pen when a ligand #inds to them
8oltage +ated
o :pen when mem#rane potential changes
echanically +ated
o :pen ia stretching
/raded Potentials
-hey are called graded #ecause the si'e of
the graded potential depends on the si'e of the
stimulus
+raded potentials can cause hyperpolari'ation or depolari'ation depending on the type of
channels that open or close
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+raded potentials occur when ion channels are opened or closed on the dendritesFcell
#ody causing ions to flowo -hese currentsFions trael to adacent sections of the mem#rane causing oltage
changes in these areas
As the graded potential spreads from the site of stimulation* the current spreads oer
larger areas and some current lea"s through #ac"ground lea" channels
o
-his is what causes the signal to decrement (decrease)
&ummation
o -he sum of all graded potentials
o !etermines whether an action potential will occur
the sum of all graded potentials will generate an action potential if the
depolari'ation is a#oe a critical leel called the threshold when it spreads
to the axon
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.ction Potentials
are large changes in mem#rane potential that occur in axons
excita#le mem#ranes hae the a#ility to generate action potential ia large rapid
depolari'ations that are used to send electrical signals long distances
strong depolari'ation ma"es 8m #ecome positie
-he process is underpinned #y changes in , a and ,@ as a result of oltage5gated a6 and
@6 channels
,hase 1 – .apid !epolari'ationo when graded potentials depolari'e 8m to threshold* there is a rapid opening of
oltage5gated a6 channels (, a OO ,@ such that a6 entry exceeds @6 exit)o 8m approaches #ut does not reach E a of 60 m8
,hase 2 – .epolari'ation
o Before 8m reaches E a* oltage gated a6 channels inactiate and oltage5gated
@6 channels open (,@ OO , a such that @6 exit will now exceed a6 entry
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o 8m moes away from E a and towards E" to the resting 8m of 5
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A#solute .efractory ,eriod (152 ms)
o -he action potential will not #e affected #y the second stimulus while a6 entry
is occurringo !uring repolari'ation* most oltage5gated a6 channels are still actiated and
cannot open
.elatie refractory period (;51; ms)
o any oltage5gated @6 channels are still open and oppose depolari'ing stimuli
o ost a6 gates are no longer actiated
Propagation of .ction Potentials
Dhen an A, is initiated at the axon hilloc"* the depolari'ation produces a current that
spreads to adacent areas of the mem#rane
o -his is #ecause the positie charges at the region of depolari'ation are attracted to
the negatie charges in neigh#oring regions
o -he spreading current depolari'es adacent regions-he neigh#oring region #ecomes depolari'ed enough to generate an A,
,ositie current moes from one axon region to the next
o A, cannot moe #ac"ward #ecause the preious region is in the a#solute
refractory state
-he speed of A, conduction increases with axon diameter* #ecause it decreases resistance
to current flow along the axon
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1altatory Conduction
A,s are rather slow eents inoling diffusion of ions
A,s can leap from one node to the next #y salutatory conduction
o -he A,s umps from one ode of .anier to another
o -he speed increases #ecause the odes are exposed to the E$% where oltage5
gated a6 and @6 channels are concentrated
o Also the myelin ma"es it much harder for current to lea" out through open ion
channels
Propagation of .Ps in Myelinated .!ons
A,s are generated the same way* though the depolari'ing current flows rapidly overlonger distances #ecause of the insulation proided #y myelin
odes of ranier are spaced such that there is enough current remaining to #ring the next
ode to threshold
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Myelination
:nly erte#rates hae myelinated axons
Adantages include
o uch higher conduction elocity
o &aes space axons can #e much thinner for a gien conduction elocity
o eta#olically cheaper A,s occur only at nodes* so oltage5gated channels and
A-,ase are only needed at nodes
.P 1timulus 5ntensity
All action potentials are the same si'e
o &o stimulus intensity is encoded #y action potential fre9uency
o &tronger* longer5lasting graded potentials (i/e/ stimuli) produce more action
potentials (i/e/ increased fre9uency)
Bio 2A03 – Lecture J
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1ynapses
3 common synapses
o Axodendritic synapse #etween an axon and a dendrite
o Axosomatic synapse #etween an axon and a cell #ody
o Axoaxonic synapse
#etween 2 axons&ynaptic cleft
o &pace #etween a pre5 and a post5synaptic terminals
2 types of synapses
o Electrical
o $hemical
Electrical 1ynapses
$an occur from neuron to neuron or neuron to glia
:ccurs ia gap unctions (cytoplasms of 2 neurons are connected)
o direct cytoplasmic connections #etween pre and post5synaptic cells that allow
electrical signals to #e transmitted from one neuron to another
Adantages
o Allow for rapid communication #etween cells
o &ynchroni'e actiity of connected cells
!isadantages
o :ften #idirectional communication
o o capacity for modulation or amplification of the signal (i/e/ signal in
presynaptic cell ? signal in postsynaptic cell)
Chemical 1ynapses
Arrial of an action potential leads to neurotransmitter release into the synaptic cleft
eurotransmitter #inds to receptors on the post5synaptic mem#rane and causes a response
$an #e neuron5neuron or neuron5effector cell (ex/ muscleFgland)
Adantages
o Knidirectional
o %acilitate integration
!isadantage
o .elatiely slow
Chemical 1ynaptic Transmission
1) Action potential2) 8oltage5gated $alcium channels open
3) $a26 entry triggers esicle doc"ing and secretion (this is where most of the delay comes
from)
7) eurotransmitter diffuses and #inds to receptor
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;) .esponse in cell
a/ :ften includes changes in permea#ility of @* a* or $l that induce a graded
potential
) !egradation #y en'ymes at multiple locations
:# .eupta"e into presynaptic terminal
a& the neurotransmitter is either degraded or recycled;# diffusion out of the synaptic cleft
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-he receptors include
o $hannel5lin"ed (ionotropic) receptors
eurotransmitter #inding causes fast changes in 8m
-he channel returns to its resting state as soon as neurotransmitter leaes
o + protein5coupled (meta#otropic) receptors
Are slow acting-he typical response is a change in 8m of the postsynaptic neuron called a postsynaptic
potential (,&,)o Excitatory ,&, (E,&,) cause depolari'ing graded potential
o Inhi#itory ,&, (I,&,) often cause hyperpolari'ing graded potential
5onotropic +eceptors
Hae a fast response
eurotransmitter #inding opensFcloses a channel directly and ion flux causes a graded
potentialo -he resulting depolari'ation is called a fast postsynaptic potential
o any fast E,&,s result from opening ionotropic receptors selectie for #oth a6
and @6 &ince the resting 8m is closer to E@ than to E a* there is a larger
electrochemical driing force (8m – Eion) on a6 than on @6
Metabotropic +eceptors* 2irect Coupling
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eurotransmitter #inds to receptor actiates + protein opensFcloses ion channels
Ex/ $losing @6 channels results in @6 haing less influence on 8m* so other lea"
conductances (a6) hae a greater relatie influence of 8m and the mem#rane
depolari'es
Metabotropic +eceptors* 'nd Messengers
eurotransmitter #inds to receptor actiates + protein actiatesFinhi#its en'yme
(effector molecule)
produces secondary messenger -he secondary messenger can then produce other cell responses or openFclose ion
channels
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5onotropic +eceptors and /.7.
+amma5amino#utyric acid (+ABA) is released at inhi#itory synapses in the $&
+ABAA receptors are channel5lin"ed receptors allow $l5 to pass through once actiated
#y ligand #inding
+ABA #inding to the +ABA receptor causes hyperpolari'ation (i/e/ I,&,) of the
postsynaptic mem#rane as $l5 enters
.educes the pro#a#ility than an action potential will fire in the postsynaptic cell
o i/e/ it decreases actiity of postsynaptic cell
Anti5anxiety drugs allosterically modulate +ABAA receptors and allow more $l5 to pass
through the channel
Mechanisms that affect Neurotransmitter +elease
• A, fre9uency in the presynaptic neuron
o &uprathreshold stimuli (stimuli strong enough to cause an A, een if in therefractory period) increase A, fre9uency
o As A, fre9uency increases* =$a26>inside in the axon terminal increases
o Higher leels of =$a26>inside result in more neurotransmitter release
• Autoreceptors
o ,romote or inhi#it neurotransmitter release from the presynaptic terminal
o Are located on the presynaptic mem#rane
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• ,resynaptic %acilitation or Inhi#ition
o Axoaxonic synapses (modulatory synapses) facilitate or inhi#it neurotransmitter
release
1ummation of P1Ps
&ummation is when multiple ,&,s add together to form a stronger signal
It is necessary #ecause a single E,&, is rarely of sufficient magnitude on its own to
induce an action potential
Bio 2A03 – Lecture N
7rain
$ere#ellumo otor coordination and #alance
$ere#ral $ortex
o ,erception
o Body moement
o Integrating center
o $omplex thought processing
Brainstem
o Integrates information from cranial neres
o $ontrol center for autonomic functions
-halamus
o Integrates sensory and motor information
o &ensory relay station to cortex
Hypothalamus
o %ood inta"e
o -hermoregulation
o euroendocrine functions
o $ircadian rhythms
Cerebrospinal Fluid "C1F#
Has a similar composition to plasmaIs distri#uted #y entricular networ" of caities in #rain and spinal cord
-otal olume is 1;0 mL
De produce 7005;00 mLFday (recycled 3 timesFday)
Functional Organization of the CN1
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has an orderly arrangement of neurons
Dhite matter
o .egions with shit tons of axons
o -he lipid content of the myelin that coer the axons ma"es them appear white
+rey matter
o .egions of cell #ody* dendrites* and axon terminals clustered togethero Lac" of myelin ma"es them appear grey
o -his is where synaptic communication and integration occurs
+lial cells other than :ligodendrocytes are located in the $&
,roection %i#res
o $onnect cere#ral cortex with lower leels of #rain or spinal cord
Association %i#res
o $onnect 2 areas of cere#ral cortex on the same side of the #rain
$ommissural fi#res
o $onnect same cortical regions on 2 sides of the #rain
o -ransfer of information #etween the 2 hemisphere occurs through these$orpus callosum
o ,rimary location of commissural fi#res
o $onnects the 2 hemispheres
Cerebral Corte!
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-he cere#ral cortex is diided into 2 hemispheres which tend to control the opposite sides
of the #odyo :ne hemisphere often dominates for particular functions
o %or ex/ left #rain is dominant for hand moement which is why most people are
right5handed
Each lo#e of the cortex is su#5diided into areas that are speciali'ed for different
functions
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%unctional areas of the primary somatosensory cortex and primary motor cortex are
topographically organi'edo eigh#oring regions of the #rain control neigh#oring regions of the #ody
-he si'e of each area reflects the num#er of neural circuits deoted to each function
7rainstem
$omposed of the medulla o#longata and pons
$ontrols many autonomic functions such as respiratory system* cardioascular system
ost of the cranial neres arise from the #rainstem
o +lossopharyngeal (IP) are cranial neres that motor control swallowing and
saliary glandsQ taste
o 8agus (P) are cranial neres that motor control larynx and pharynx
1pinal Cord
A spinal nere #ranches off either side of the spinal cord and exits the erte#ral column
#etween most adacent erte#rae
-he spinal neres are designated according to where they leae the spinal cord
o $erical (J) around the nec" area
o -horacic (12) around the upper5middle area of the #ac"
o Lum#ar (;) around the lower area of the #ac"
o &acral (;) near the #uttoc"sFgonads
o $occygeal (1)
Each spinal nere traels to adacent regions of the #ody which can #e mapped #y
sensory regions on the s"in (dermatomes)
1pinal Cord = /ray Matter
Afferent axons enter gray matter of spinal cord ia dorsal roots with cell #odies in dorsal
root ganglia (pseudo5unipolar neurons)
Efferent neurons hae cell #odies in the grey matter and their axons leae the spinal cord
ia entral roots (multipolar neurons)
!orsal and entral roots merge at a short distance from the spinal cord to form the spinal
neres
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1pinal Cord = 6hite Matter
-he white matter consists of ascending and descending tracts of axons that proide
communication #etween the #rain and spinal cord* or #etween leels of spinal cord
All tracts are #ilateral
Afferent or efferent neurons will usually synapse with interneurons in grey matter* which
proect along tracts within white matter
Ascending and descending tracts generally cross to the opposite side of origin (the
contralateral side) although some exceptions exist where they remain on the same side
(ipsilateral)
+efle!es
Automatic patterned responses to stimuli that do not re9uire conscious interention are
called reflexes
.eflex arcs consist of fie components
o &timulus sensory receptor afferent neuron integration center efferent
neuron effector organ response
1tretch +efle!
-he patellar tendon stretch reflex is the only monosynaptic reflex in the human #ody
-he muscle spindle senses stretching which triggers action potentials in afferent neurons
&ynapses with efferent neurons in spinal cord (integration centre)
o Excitatory connection with efferent neurons to the 9uadriceps
o Inhi#itory connection with afferent neurons to the hamstrings
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$ontraction of the 9uadriceps muscle and relaxation of the hamstrings shortens the
9uadriceps muscle
6ithdra-al and Crossed4E!tensor +efle!
-his is the reflex you experience if you accidently step on a sharp o#ect-he reflex arc for this reflex is
o &timulus sharp o#ect
o &ensory receptor nociceptor
o Afferent neuron
o Integration centre spinal cord
o Efferent neuron
o Effector organ 9uadriceps and hamstrings
o .esponse :K$HR
8oluntary Movements
oement is controlled #y oluntary and inoluntary pathways
-he pyramidal tracts which proect from the motor cortex* control the fine oluntary
moements of the extremities
:ther tracts and #rain regions control the core and nec" muscles for oluntary moement*
posture* and #alance
1ensory +eceptors
Are classified #ased on the mode of stimulus they detect
o
,hotoreceptors
lighto $hemoreceptors chemicals from taste* smell etc
o -hermoreceptors temperature
o echanoreceptors i#rations* sounds* touch
Baroreceptors detect #lood pressure and regulate the heart and asculature
$hemoreceptors sense :2* $:2* and pH of the #lood and regulate #reathing
&tretch receptors sense stomach distension after a meal
&ensory receptors can #e speciali'ed endings of afferent neurons or a separate cell that
synapses with an afferent neuron
&ensory unit
o
$omprises a single afferent neuron and all of the receptors with which it isassociated
-he receptor potential is the graded potential induced #y a stimulus in a sensory receptor
o &ensory receptors tend to adapt oer time
-he strength of the signal gradually decreases oer time
o Information a#out stimulus intensity is transmitted #ased on action potential
fre9uency
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1ensory 1ystems
Afferent neuron transmits sensory information to the $&
A single afferent neuron can dierge to seeral second5order interneurons
&econd5order interneurons can receie and integrate signals from many different neurons
o -his is called conergence
any #ut not all interneurons transmit information to the thalamus* a maor relay centre
for sensory input
Temperature +eceptors
-emperature receptors in the s"in are free nere endings for which action potential firing
is sensitie to temperature
-hermoreceptors
o &ense s"in temperature in the normal physiological range for s"in from 20 to
7;$o -emperature nociceptors detect tissue5damaging temperatures (O7;$)
-he 2 types of thermoreceptors are
o Darm receptors (3057;$)o $old receptors (2053;$)
-emperature sensitie transient receptor potentialC (-.,) ion channels underlie
temperature sensation
Temperature +eceptors
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-hermoreceptor afferents (receptors 6 afferent neurons) synapse with interneurons in the
spinal cord
-he thermal signal is sent to the thalamus where it is relayed to other parts of the #rain
8ision and Photoreceptors
,hotoreceptors are light sensitie receptors
o .ods detect dim light and do not distinguish colours
o $ones detect #right light and underlie colour ision
3 types of cones which are #est suited to detect red* #lue* green
Light detection #y rhodospin influences the actiity of a +5protein* which regulates the
opening of ion channels
Light is sensed #y a reduction in the action potential fre9uency of afferent neurons
Light stimuli reduce +5protein actiation* close a6 hcnnales* hyperpolari'e the
receptor* and reduce the stimulation of #ipolar cells
,hotoreceptors synapse with #ipolar interneurons in the eye* which synapse with neuronsin the optic nere
o Light must trael seeral cell layers #efore reaching the photoreceptors
-he optic nere (cranial nere II) transmits information to the thalamus* which is then
relayed to the isual cortex
)ecture %>
.utonomic Nervous 1ystem
• $ontrol areas are located in the #rainstem and hypothalamus
• $ontrol areas receie afferent neural information from sensory afferents (Eg/
$hemoreceptors* #aroreceptors) and higher #rain centers (eg/ -halamus)
• &ympathetic erous &ystem (&&)
o Actie during periods of excitation or physical actiity
o Has a large influence on the cardioascular system (fight or flight response)
• ,arasympathetic erous &ystem (,&&)
o Actie during periods of rest
o &timulates digestie organ systems
o inhi#its the cardioascular system (rest and digest)• && and ,&& innerate many of the same organs* #ut usually hae opposing effects
.natomy of the .N1
,re5+anglionic %i#res
o $ell #ody in the #rainstem or spinal cord
o -hinly myelinated axon proects to autonomic ganglia
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Autonomic +anglia
o Are located at the target organ in the ,&&
o ,araerte#ral (next to erte#ral column) in the &&
,ost5+anglionic %i#res
o $ell #ody in the autonomic ganglia
o Knmyelinated axon proects to isceral effector organs
Parasympathetic Nervous 1ystem "P1N1#
,&& efferent signals are transmitted primarily in the agus (cranial nere P)* as well as
other cranial neres and the pelic nere
,re5ganglionic neurons pass uninterrupted to the target organ
,ost5ganglionic neurons are ery short and innerate the target tissue
%inal neurotransmitter is always acetylcholine (A$h)
P1N1 Neurotransmitters and +eceptors
A$h receptors
o icotinic receptors
Are ionotropic receptors expressed #y all post5ganglionic neurons
Hae high affinity for nicotine found in to#acco
o uscarinic receptors
Are meta#otropic receptors expressed at the effector organ
Hae high affinity for muscarine found in toxic mushrooms
A$h action at synapses is short lied #ecause it is rapidly #ro"en down #y
acetylcholinesterase
o A$h does not circulate in the #lood #ecause the #lood contains high5actiity non5specific cholinesterases
1ympathetic Nervous 1ystem "1N1#
&& efferent signals are transmitted ia spinal neres
,re5ganglionic neurons exit the spinal cord and synapse with post5ganglionic neurons in
the && ganglia within the Ssympathetic chainG
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,ost5ganglionic fi#res leae the sympathetic chain (or collateral ganglion) to innerate
the target tissue
%inal neurotransmitter is usually noradrenaline (norepinephrine)
1N1 Neurotransmitters and +eceptors
Acetylcholine (A$h) is released from pre5ganglionic neurons and act on nicotinic
receptors expressed #y post5ganglionic neurons
,ost5ganglionic sympathetic neurons release norepinephrine
o -he chromaffin cells of the adrenal medule release J0M adrenaline* 20M
noradrenalin and small amounts of dopamine
Effector organs that respond to norepinephrine or epinephrine express adrenergic
receptors
.drenergic +eceptors
Are meta#otropic receptors and #ind #oth epinephrine and norepinephrine
2 classes of adrenergic receptors
o Alpha () adrenergic receptors
1 and 2 su#classes
o Beta (T) adrenergic receptors
T1* T2* and T3 su#classes
&ignal transduction mechanism for 1 (,I,2) differs from 2 and all the T su#classes
o $hec" slide 10 of Lecture 11
)ecture %'
Types of Muscles
&"eletal uscle
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o $onnected to at least 2 #ones
o &ome exceptions include some facial muscles* larynx* urethral sphincter
&mooth uscle
o o striations
o %ound in #lood essels* +astrointestinal tract* uterus
$ardiac uscleo &how characteristics of #oth s"eletal and smooth muscles
1$eletal Muscle 1tructure
-he cells are called muscle fi#res* due to their elongated shape* and are diided into
#undles (SfasiciclesG) #y additional connectie tissue (perimysium and endomysium)
-endons are continuous with the other layer of connectie tissue (epimysium)
uscle fi#res are multinucleated cells
o each fi#re is controlled #y only 1 motor neuron
- tu#ules proect inwards from the fi#re surface
yofi#rils contain the contractile machinery
&acroplasmic reticulum is distri#uted throughout cyoplasma
itochondria are situated in 2 locations
o &u#sacrolemmal next to sacrolemma
o Intermyofi#rillar interspersed with myofi#rils
The 1acromere
&"eletal (and cardiac) muscle is striated due to the orderly arrangement of thic" and thin
filaments in myofi#rils
U5lines &acromeres are #ordered #y U5lines* which anchor the thin filaments (actin)
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– line-hic" filaments (myosin) are oined at the 5line ( for myosin) and are
anchored #y titin
A #and a region of thic" filaments (myosin)
H 'one region #etween opposing ends of thin filaments
I #and regions of thin filaments that do not oerlap myosin
Thin Filaments
Bac"#one is composed of actin
+5actin (for glo#ular protein) #ind together to form %5actin (fi#rous protein)
-ropomyosin partly coers the myosin cross5#ridge #inding site when the muscle is
relaxed
-roponin regulates the location of tropomyosin in response to $a26 during muscle
contraction
Thic$ Filaments
are made of myosin protein* composed of a head region with A-,ase actiity and actin
#inding site ($ross#ridge)
each myosin protein is a dimer of 2 inter5twined su#units
A thic" filament is composed of hundreds of myosin proteins* with heads staggered along
the filament
-he &liding %ilament odel
o uscle shortening occurs as thic" and thin filaments slide past each other
The Crossbridge Cycle
1) yosin #inds to actin
• Dhen myosin is in its energi'ed state (when A!, and ,I are #ound)* it has a high
affinity for actin
• -his step only occurs when $a26 is present
2) ,ower stro"e
• -he #inding of myosin to actin triggers the release of , I and later A!, from the
A-,ase site of myosin
• !uring the process* the myosin head piots towards the middle of the sacromere
and pulls the thin filaments along with it
• -he conformational change shifts myosin into its low5energyC state3) .igor
• In its low energy form* myosin are tightly #ound
• -his is the cause of Srigor mortisG the stiffening of the #ody after death* which
lasts until the myofi#rils #rea" down
7) yosin and Actin un#ind
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• -he #inding of A-, to myosinGs A-,ase site triggers a conformational change in
the protein
• -he affinity of myosin for actin decreases* so the myosin detaches
;) $oc"ing of the myosin head
• &oon after A-, #inds* it is hydroly'ed to A!, and ,i
• -he energy released shifts myosin into its energi'ed state
) Energi'ed myosin #inds to actin and the cycle continues as long as $a26 is present
• $a26 is essential for cross#ridge attachment
• -he #inding of $a26 to troponin causes a conformational change in the complex
• -ropomyosin shifts from its tresting position* uncoering the myosin cross#ridge
#inding sites
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E!citation4Contraction Coupling
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1) A$h is released from the axon terminal of a motor neuron and #inds to receptors in the
motor end plate
• -his #inding elicits an end5plate potential* which triggers an action potential in
the muscle cells
2) Action potential propagates along the sarcolemma and down - tu#ules
• Action potentials target charged amino acid residues on !H, receptors• $onformational change in !H, (dihydropyridine) opens the ryanodine receptor
channel it is associated with
3) -he action potential triggers $a26 release from &acroplasmic reticulum (&.)
• $a265induced $a26 release some of the $a26 #inds to other &. $a26 channels
and causes them to open
7) $a26 #inds to troponin* exposing myosin5#inding sites;) $ross#ridge cycle #egins (i/e/ muscle fi#er contracts)
) $a26 is actiely transported #ac" into lumen of &. following the action potential
is rising
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.elaxation ,hase
o cytosolic =$a26> is decreasing (reupta"e into &.)
A single twitch is reproduci#le in magnitude and shape
Fibre 2iameter
-he capacity of a muscle fi#re to generate forceFtension depends on its diameter
Larger diameter fi#res can generate more force #ecause they contain more sacromeres
(thic" and thin filaments)
-he num#er of thic" and thin filaments per unit cross5sectional area is constant* so
changing area is the #est way to increase strength
Fibre )ength
the length of a muscle fi#re* relatie to resting length* also affects force generation
force generation #y a sacromere is maximal at the length when all of the myosin cross5
#ridges can #ind to actin
force generation falls when the sacromere is so short that thin filaments start oerlapping
force generation also falls when some or all of the cross5#ridges cannot #ind to actin
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Motor nit
• groups of fi#res innerated #y a single motor neuron
o one neuron innerates many fi#res
Muscle Fibre +ecruitment
most muscle contraction is not to maximum effort (i/e/ it is su#5maximal)
the $& regulates the amount of force generated #y regulating the num#er of motor units
that are recruitedC to contract
o more motor units ? greater force
-he &i'e ,rinciple
o otor units with fewer and small fi#res are recruited #efore those with more and
large fi#reso -his occurs #ecause neurons from larger motor units hae larger cell #odies
o Larger cells are harder to depolari'e to threshold* and thus re9uire more intense
stimulation from the $& to generate an action potential
o -his contri#utes to the precise control of muscular force
1$eletal Muscle Metabolism
!ifferent energy source predominate after different durations of exercise
o $reatin phosphate ($r,) Anaero#ic glycolysis :xidatie ,hosphorylation
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1$eletal Muscle Fibre Types
uscle is composed of different fi#re types* which differ in contraction speed and
meta#olic phenotype
:xidatie fi#res hae a high mitochondrial a#undance and primarily use aero#ic
meta#olism (oxidatie phosphorylation)+lycolytic fi#res hae fewer mitochondria and support contraction with anaero#ic
meta#olism (glycolysis)
3 main fi#re types
o &low oxidatie (-ype I) slow contracting* high aero#ic capacity
o %ast oxidatie (-ype IIa) fast contracting* high aero#ic capacity
o %ast glycolytic (-ype II#) fast contracting* low aero#ic capacity* high
glycolytic capacity
-he differences in contraction elocity exist #ecause each fi#re type expresses different
myosin isoforms
!ifferent muscles hae different fi#re type compositionso uscles with primarily type II# fi#res (extraocular muscle) contract much faster
than muscles with mostly type I fi#res (soleus)
o uscles with primarily type IIa fi#res +astrocnemius
any muscles hae a mixture of fi#re types
Muscle Fibre Type +ecruitment
In muscles with a mix of fi#re types* the first fi#res to #e recruited are type I fi#res then
type IIa fi#res
o -his is related to the si'e of their motor units
-ype II# are usually only recruited when large amounts of force are needed
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• In #ird flight muscle* which do not contain type I fi#res* type IIa fi#res support steady
flight whereas type II# fi#res are only used for ta"eoff
)ecture %'Muscle 1pindles
uscle spindles are composed of a small num#er of modified muscle fi#res (intrafusal
fi#res) that are innerated #y sensory neurons
Dhen the muscle lengthens* the intrafusal fi#res are stretched* which induces action
potentials in the sensory neurons in proportion to the degree of stretch
/olgi Tendon Organ
+olgi tendon organs (+-:) are capsules of connectie tissue intertwined with collagen
fi#res in tendons
Dhen the muscle stretches the tendons* the +-:s are actiated* increasing the action
potential fre9uency in proportion to the tension in the tendon (and thus* the muscle)
Other Muscle Types
&"eletal and cardiac muscles are striated* #ut smooth muscles are not
&"eletal muscle is innerated #y somatic (motor) neurons* #ut smooth and cardiac
muscles are innerated #y autonomic neurons
o -his means that the s"eletal muscle is the only muscle that you can control
yourself
1mooth Muscle All muscle types contain thic" and thin filaments and generate force through the cross5
#ridge cycle
-hic" and thin filaments in smooth muscles are oriented at o#li9ue angles and are not
arranged in sacromeres
Instead of toponin and tropomyosin* excitation5contraction in smooth muscle inoles
$a26 #inding to calmodulin* which actiates myosin light chain "inase
yosin light chain "inase phosphorylates and actiates myosin A-,ase
Large influx in $a26 is what causes the contraction in smooth muscles
7lood +eading .ssignment "pg& ?('4?(;#
7ruises "Contusions#
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Are caused #y damage to #lood essels which allows #lood to escape into the tissues
-he more #lood that lea"s into the tissues* the #igger the #ruise
-he closer the #lood essel damage is to the s"in* the more colorful the #ruise
$onersion of hemoglo#in to #ile is what changes the colours of the #ruise
Plasma
Li9uid portion of #lood
-ransports proteins* hormones* electrolytes* organic nutrients and waste products
Erythrocytes
$ellular components of the #lood (.B$)
-ransport oxygen and car#on dioxide
)eu$ocytes
Dhite #lood cells
!efend the #ody against pathogens
Platelets
Are cell fragments which are critical in the formation of #lood clots to preent loss of
#lood
Hematocrit
%ractional contri#ution of the erythrocytes to the #loodIs determined #y centrifuging a sample of #lood in a tu#e and is represented as a
percentage
Dhen centrifuged* the elements of the #lood are separated #ased on density
o Because erythrocytes are denser than other elements of the #lood* they are pulled
to the #ottom of the tu#e
o ,lasma* the least dense component* remains at the top
o Between these layers is the #uffy coat (layer of leu"ocytes and platelets)
:ur #lood is mostly made of erythrocytes and plasma and ery little leu"ocytes and
platelets
%or men* the normal range of hematocrit is 725;2M while for women* it is 3
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o -his is a normal adaptie response in low5oxygen enironments* such as high
altitudes
Plasma
A9ueous solution in which solutes are dissoledo &olutes include proteins* small nutrients* meta#olic waste products* fases* and
electrolytes
o ,roteins are the most a#undant solutes in plasma #y weight #ut the smaller solutes
are present in higher concentrations
,lasma has a similar composition to interstitial fluid in terms of solutes #ecause the
capillary walls that separate these two are highly permea#le to small solutes
o ,lasma and interstitial fluid differ significantly with respect to protein
concentrations
o -his is due to low permea#ility to proteins
,lasma proteins are categori'ed into 3 main groupso Al#umins
&ynthesi'ed #y the lier
ost a#undant plasma proteins
ale a large contri#ution to the osmotic pressure of plasma* which affects
the moement of fluid across capillaries
o +lo#ulins
-ransport lipids* steroid hormones* and other su#stances in the #lood
,lay a critical role in the #loodGs a#ility to form clots
Important in defending the #ody against foreign su#stances
o
%i#rinogen&ynthesi'ed #y the lier
@ey su#stance in the formation of #lood clots
&erum is plasma from which fi#rinogen and other clotting proteins hae #een remoed
Erythrocytes
Are most a#undant cells in the #lood
-hey lac" nuclei* mitochondria* and other organelles such as ri#osomes necessary for
manufacturing proteins
-heir shape is a #iconcae dis" which is due to the presence of cytosolic protein called
spectrino &pectrin is a fi#rous protein that forms a networ" lin"ed to the plasma mem#rane
o -he spectrin net is flexi#le* giing erythrocytes the a#ility to #end and flex as
necessary to moe through capillaries
o In addition to the flexi#ility* the #iconcae shape gies erythrocytes a large
surface area which ma"es them suita#le for exchange
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O!ygen and Carbon 2io!ide Transport
Erythrocytes delier oxygen from lungs to respiring cells
Erythrocytes delier car#on dioxide from respiring cells to lungs
Erythrocytes hae a high capacity for carrying these gases #ecause their cytoplasm
contains two proteinso Hemoglo#in
Binds and transports oxygen and car#on dioxide
o $ar#onic Anhydrase
-ransports car#on dioxide only
Hemoglobin3s +eversible 7inding of O!ygen and Carbon 2io!ide
Hemoglo#in is composed of 7 polypeptide chains of 2 types (2 alpha and 2 #eta chains)
each of which has an iron5containing structure "nown as a heme group
-he iron in hemoglo#in is present in the ferrous form (%e26) which imparts a red color to
the erythrocytes and hence to the #lood
-his iron is the site to which a molecule of oxygen #inds
Each hemoglo#in can #ind to 7 oxygens #ecause there are 7 heme groups in each
hemoglo#in molecule
$ar#on dioxide #inds reersi#ly to amino acids within the polypeptide chains howeer
hemoglo#in transports considera#ly less car#on dioxide than oxygen
Carbonic .nhydrase and the Carbon 2io!ide47icarbonate +eaction
$ar#onic anhydrase is an en'yme that cataly'es the reersi#le conersion of car#on
dioxide and water to car#onic acid
-he pathway continues with the reersi#le dissociation of car#onic acid to yield a H ion
and a #icar#onate ion
$ar#on dioxide can #e conerted to free H ions which affects the pH of the #lood
Effects at High .ltitude
Dhen oxygen leels in the #lood are low* more erythrocytes are produced
-he larger num#er of erythrocytes transports more oxygen to the tissues that need them
-his is why athletes train at higher altitudes where oxygen is less than sea leel
Athletes also increase their num#er of erythrocytes #y directly inecting #lood cells into
their system or inecting erythropoietin* the chemical that stimulates erythrocyte synthesis
Increasing the concentration of erythrocytes increases resistance to #lood flow
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o -he increasing resistance can increase friction #etween #lood and the walls of the
#lood essels wea"ening the walls and ma"ing them more suscepti#le to
atherosclerosis
)ife Cycle of Erythrocytes
Erythrocytes remain for only a#out 120 days
-hey cannot undergo cell diision #ecause they donGt hae nucleus or cell organelles
Erythropoiesis process #y which the #one marrow produces erythrocytes
Erythrocyte Production
All #lood cells deelop from precursor cells called hematopoietic (#lood forming) stem
cells located in the #one marrow
Erythrocytes and most leu"ocytes come to full maturity in the #one marrow
- lymphocytes migrate to the thymus gland #efore they deelop to maturity
Hematopoietic +rowth %actors (H+%s) are cyto"ines that are responsi#le for
deelopment of specific #lood cellso Erythropoietin is H+% that stimulates erythrocyte production
o $olony5stimulating factors and interleu"ins are H+%s inoled in leu"ocyte
production
Erythropoietin is released in response to low oxygen leels in the #lood
Erythropoietin traels in the #loodstream to the #one marrow* where it triggers
differentiation of pluripotent cells to erythrocytes
o !uring differentiation* erythrocytes produce hemoglo#in and lose their nuclei and
organellesthe last cell stage prior to deelopment into the mature erythrocyte is the reticulocyte
which is a .B$ with some ri#osomes still present in the cytoplasm giing the cell a
we#li"e (or reticular) appearance
Knder normal conditions* only erythrocytes are released into the #lood stream
Iron is needed for hemoglo#in synthesis
o Iron can #e receied from iron* folic acid* itamin B12
o &ome iron is stored in the lier and some is recycled from old erythrocytes
.nemia
$ondition where the oxygen carrying capacity of the #lood is reduced
$an happen due to a reduction in the amount of hemoglo#in per cell or reduction in the
num#er of erythrocytes in the #lood
Filtering and 2estruction of Erythrocytes by the 1pleen
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&pleen is a lymphoid organ that stores #lood cells and remoes old erythrocytes from the
circulation
&ome old erythrocytes are hemoly'ed in the #loodstream #ut most are engulfed #y
macrophages in the spleen and lier
Dhen macrophages destroy erythrocytes* hemoglo#in is cata#oli'ed
o After iron is remoed* the resulting heme is conerted to #iliru#in (yellow)
o -he #iliru#in traels to the lier where it is cata#oli'ed further
o ost products of the cata#olism are released into the small intestines and
ultimately excreted in the feces
o Vaundice is the result of increased #iliru#in leels in the plasma due to excessie
erythrocyte hemolysis
Iron that was released #y hemoglo#in cata#olism is recycled to form new hemoglo#in
Iron is transported in #lood #ound to a protein called transferrin
o -ransferrin pic"s up ion from the +I tract or from the spleen and transports the
iron to the red #one marrow for erythrocyte production* or to the lier where some
iron can #e stored #ound to the protein ferritin
)ecture %(
Need for Circulatory 1ystem
!iffusion times (t) are proportional to the distance (x)2 oer which diffusion occurs
!iffusion is to slow to transport nutrients and gases in humans so circulatory system is
needed to do this o#
Circulatory 1ystem
A fast conection system that rapidly circulates fluids #etween surfaces in contact with
the external milieu and cells deep inside organisms
.oles of a circulatory system include
o !istri#ution system
!issoled gases and molecules for nutrition* growth and repair
o $hemical signaling* heat dissipation etc/
/eneral )ayout of the Circulatory 1ystem
• ,ropulsie :rgan Arterial &ystem $apillaries 8enous &ystem ,ropulsie
:rgan
• ,ropulsie :rgan (heart)
o $reates the pressure driing #lood flow
o Also has sensory and endocrine functions
• Arterial &ystem
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o !istri#utes the #lood
o Helps regulate #lood pressure
• $apillaries
o Location of gas and nutrient exchange
• 8enous &ystem
o .eturns #lood to hearto Acts as a #lood olume reseroir
Mammalian Circulatory 1ystem
Is composed of 2 circuits
,ulmonary $irculation
o +oes to the lungs
o ,ic"s up oxygen at the lungs
o Is a low pressure system (20 mmHg)
o .ight entricle lungs left atrium
&ystemic $irculation
o !eliers oxygen to other organs and tissues
o High pressure system (100 mmHg)
o Left entricle tissues right atrium
Both circuits hae an arterial (#lood traels away from the heart) and a enous system
(returns #lood to heart)
Blood flow is e9ual in each circuit (; LFmin)
Blood flows in series from the pulmonary to the system circulation
o All #lood flows through one* then the other
Blood in systemic circulation flows in parallel to each organFtissue
o Blood leaing the left entricle flows through the ascular #ed of only one organ
#efore returning to the heart
-he heart receie its own parallel circulation from the coronary artery
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7loc$age in Circumfle! Coronary .rtery
If there is a #loc"age in the coronary artery* the heart wonGt get enough oxygen
-he inade9uate #lood flow to the cardiac tissue can cause heart attac"
The Heart
Is composed of 3 layers
o Epicardium outer connectie tissue
o yocardium cardiac muscle
o Endocardium endothelium that extends throughout the cardioascular system
-he left entricle is much thic"er than the right entricle #ecause the heart needs to wor"
harder when the pressure gets higher/ In order to send the #lood out* high pressure is
needed/
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Papillary Muscles
-end to pull the aortic ale to allow #lood flow
-hese muscles contract when entricles contract
-hese muscles do not cause the ale to open* they are causing the ale to not collapse
Dhen entricles contract* the papillary muscles contract closing the aleAortic ales are ery rigid to resist collapsing into the entricle
Cardiac Cycle
-he series of eents that occur during one full cycle of contraction and relaxation
,hases of the cycle are delineated #y the opening and closing of the heart ales and are
characteri'ed #y changes in pressure and olume
&ystole
o ,eriod of entricular contraction
!iastoleo ,eriod of entricular relaxation
0no- Figures %(4%; and %(4%< "slide %%#
Cardiac Output
$ardiac output ? stro"e olume x heart rate
$ardiac output at rest is approximately ; LFmin
End5!iastolic 8olume (E!8) pea" olume
End5&ystolic 8olume (E&8) lowest olume
&tro"e 8olumeo 8olume of #lood eected with each heart #eat
o &8 ? E!8 – E&8
&ystolic ,ressure
o ,ea" aortic pressure caused #y entricular contraction
!iastolic ,ressure
o Lowest aortic pressure
ean Arterial ,ressure
o A, ? (&, 6 2!,)F3
Heart 1ounds
-he heart sounds are the sounds of ales closing* not the sound of heart contracting or
#lood moing
Pulse
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-he pressure pulse created #y the pea" pressure during entricular contraction is
propagated along the eins
Cardiac Muscle
-here are 3 cell ty