all lectures (1)

8/16/2019 All Lectures (1)

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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


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


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



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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

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