Physio Chino

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`JPGEsteban PediaNotesPhysiology NotesChino Espino, MD

1All rights reserved. 2010.

Cell PhysiologyCell Membrane Structure and Components1. MOST abundant compontents are phospholipids and proteins Phospholipids hydrophilic head (glycerol) + hydrophobic tail (2 fatty acyl chains)form a BILAYER hydrophilic surface and hydrophobic interior

lipid soluble molecules dissolve through bilayer readily pass through bilayerwater soluble molecules will NOT dissolve through bilayer require channels

Proteins maybe intrinsic/integral or extrinsic/peripheral

Intrinsic / Integral Extrinsic / Peripheral

spans the ENTIRE membranelocated on ONLY 1 SIDE of themembrane (either internal or external)

attached via HYDROPHOBIC

interactions

attached via CHARGE

INTERACTIONS disrupted viadisrupted by DETERGENTS

disrupted by changing the IONICCOMPOSITION / pH of the medium

NOTE: membrane proteins are ASYMMETRIC domains outside and inside of cell are

DIFFERENTe.g. Na

+/K

+/ATPase and Ca2

+/ATPase pumps

2. Cholesterol stabilizes the cell membraneFLUIDITY BUFFER

3. Glycolipids and Glycoproteins function in cell-cell communication, and as receptorsand antigens

Glycolipids Glycoproteins

CHO bound to membrane LIPIDS CHO bound to membrane CHON

e.g. Receptor for Cholera Toxin (GM1)e.g. Fibronectin attachment to

extracellularmatrix

Fluid Mosaic Model some components CANNOTMOVE:

remain in 1 part of the cell membrane tethered by the cytoskeletone.g. anion exchanger in RBC tethered by ankyrin to spectrin

Ach receptors

DENERVATION SUPERSENSITIVITYif nerve to muscle is disrupted, Ach receptors spread throughout the musclemembrane sensitity to Ach


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some components CAN MOVE in the membrane:along the PLANE of membrane more rapid and spontaneousFLIP-FLOP between 2 monolayers less rapid, limited to small lipid-soluble molecules

Cellular Transport

PASSIVE TRANSPORTNO energy needed

ACTIVE TRANSPORTREQUIRES energy

SimpleDiffusion

FacilitatedDiffusion

Primary ActiveSecondaryActive

Endocytosis/Exocytosis

PassageTHROUGHmembrane?

YES YES YES YES NO

EnergyUSAGE? NONE NONE YES YES YES

What drivestransport?

random thermal motion ofparticles (Brownian motion)until concns are EQUAL

energy fromATP

energy from Na+

gradientenergy fromATP

CarrierMediated?

NO YES YES YES NO

Movement ofSolute

down gradientdowngradient

againstgradient

against gradient variable

Exampleswaterurea

ion channelsGlc transport

Na+/K

+/ATPase

Ca2+/ATPase

SYMPORT:Na

+/Glc and

Na+

/K+

/2Cl-

cotransport

ANTIPORT:Na

+/H

+, Na

+/C

2+

and Cl-/HCO3

-

exchange

LDL receptors

DiffusionDiffusion Coefficient (ABILITY to DIFFUSE)

r6KTD

Determinants of Diffusion Coefficient

1. KT: average kinetic energy of particles2. 6r: viscous drag during movement of particles

size of molecule (r): size : diffusion

3 MW

1r i.e. 8x MW is equivalent to only 2x )8(3 in diffusion

viscosity of medium (): viscosity : diffusion


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Ficks Law (RATE of DIFFUSION)

x

CDAJ

Determinants of Ficks Law

1. D: diffusion coefficient2. A: surface area for diffusion

3. C: concentration gradient ALWAYS compute C = (higher lower)4. x: thickness of membraneRULE OF THUMB:

x m in thickness x2 mS decrease in diffusion timee.g. 10 m increase in thickness = 100 ms (10

2) decrease in diffusion time

Summary of Factors that affect DiffusionINCREASES Diffusion DECREASES Diffusion

Lipid Solubilityoil:water partition coefficient HIGH LOW

Concentration Gradient HIGH LOW

Thickness of Membrane THINNER THICKER

Surface Area HIGH LOW

Size of Particles SMALL particles (low MW) BIG particles (high MW)

Temperature HIGH LOW

NOTES Can water-soluble substances move through membranes? through gaps between phospholipids if they are SMALL enough through water channels (aquaporins)

Osmosis simple diffusion of WATER through a SEMI-PERMEABLE membrane from LOW

SOLUTE to HIGH SOLUTE concentration

membrane must be permeable to water but NOT to solute if solute is permeable then it isNOT an effective osmole

Osmotic Pressure: HIGHER osmotic pressure : HIGHER water flow

)i(cRT Determinants of Osmosis1. c: MOLARITY2. R: gas constant (0.0821 L.atm/mol.K)3. T: temperature4. i: coefficient to determine EFFECTIVE osmoles (i.e. effectivity of

dissociation of ions)


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Osmolarity vs. TonicityOsmolarity Tonicity

refer to COMPUTED OSMOTIC PRESSUREcomputed via freezing point depression

HYPEROSMOLAR: GREATER

ISOSMOLAR: EQUAL

HYPOSMOLAR: SMALLER

refer to CONCENTRATIONS EFFECTON VOLUME

HYPERTONIC: causes SHRINKINGISOSMOLAR: NO EFFECTHYPOSMOLAR: causes SWELLING

refer to BOTH PERMEANT andIMPERMEANT solutes

refer ONLY to IMPERMEANT solutes

Notes: STEADY-STATE cell volume is determined ONLY by IMPERMEANT SOLUTES PERMEANT SOLUTES cause TRANSIENT effects only greater permeability, shorter

effect of transient changes

Reflection Coefficient reflects ease with which substance penetrates a membrane

Value is BETWEEN 1 and 0constant NEARER 1 IMPERMEABLEconstant NEARER 0 PERMEABLE

Properties of Carrier-Mediated Transport

1. FASTER than simple diffusion2. chemical SPECIFICITY include STEREOSPECIFITY e.g. L-Glucose not transported

3. SATURABLE: similar to Michaelis-Menten Kinetics in enzymes:

]S[K

]S[JJ

m

max

4. may be INHIBITED COMPETITIVE INHIBITION structural analogs ALLOSTERIC INHIBITION alters transporter affinity for substrate

METABOLIC INHIBITION inhibits Na+/K+/ATPase pump i Na+ gradient for 2oactive transport


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Ion Channels selective based on SIZE and CHARGE OF LINING

if POSITIVE charge: will repel cations, will allow anionsif NEGATIVE charge: will repel anions, will allow cations

conductance depends on PROBABILITY of opening or closingVOLTAGE-Gated regulated by membrane potentialsLIGAND-Gated regulated by chemical signals

Intercellular Connections attachments BETWEEN cells

Tight Junctions (Zonula Occludens) Gap Junctions

attachments WITHOUT a channel attachments WITH a channel

used for PARACELLULAR transport of

substances

renal distal tubule (tight/impermeable)renal proximal tubule (leaky/permeable)

used for INTERCELLULAR

COMMUNICATION

neurons (synapses)cardiac muscle

TRANSCELLULAR through the cell itselfPARACELLULAR in between cells, through tight junctions

Miscellaneous Na

+/K

+/ATPase usually BASOLATERALmaintains intracellular Na

+

2o

Active Transport uses Na+ gradient created by Na+/K

+/ATPase

Hence, inhibiting Na+/K

+/ATPase pump will indirectly inhibit 2

otransport mechanisms

Kinds of ATPases

P-Type V-Type F-Type

MOAuses aPhosphorylatedintermediate

accumulates H+

synthesizes ATP from H+

gradient

ExamplesNa

+/K

+/ATPase

Na2+/ ATPase

in lysosomes maintains acidicenvironmetn

in inner mitochondrialmembrane as part ofoxidative phosphorylation


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MEMBRANE POTENTIALSDIFFUSION / ELECTROCHEMICAL POTENTIAL potential difference (electrical potential) created by diffusion of an ion down its

concentration gradient (chemical potential) can be generated ONLY by PERMEANT

ions

MAGNITUDE depends on CONCENTRATION GRADIENTSIGN depends on CHARGE OF DIFFUSING ION and DIRECTION OF

MOVEMENT

net movement of ions depends on which is larger(potential difference vs. concn gradient)

EQUILIBRIUM POTENTIAL a KIND of DIFFUSION POTENTIAL

diffusion potential where electrical potential is EQUAL AND OPPOSITE TO chemicalpotential leading to NO NET MOVEMENT OF IONS!

Nernst Equation: used to calculate for the EQUILIBRIUM potential of a particular ion

extra

raint

]A[

]A[ln

zF

RTE

Determinants of E1. [A]: concentration of ions

2.F

RT: constant that depends on TEMP (~60 mV at 37

oC)

3. z:CHARGE of the ion

NOTES: the equilibrium potential DIFFERS per ION CHARGE of the potential refers to charge RELATIVE TO INTRACELLULAR compartment:

if E is NEGATIVE INTRACELLULAR more () if E is POSTIVE INTRACELLULAR more (+)

Relationships in the Nernst Equation

EEqand MEASURED Ehave the SAME sign

EEq> MEASURED Eelectrical and chemicalpotential OPPOSING, BUTelectrical > concentration

EEq< MEASURED Eelectrical and chemicalpotential OPPOSING, BUTelectrical < concentration

EEqand MEASURED E have OPPOSITE signs electrical and chemicalpotential SAME direction

VERY FEW ions are needed to achieve equilibrium


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RESTING MEMBRANE POTENTIAL from the contributions of the equilibrium potentials of ALL permeant ions

Equilibrium Potentials

ENa = + 65 mVECa = + 120 mV

Resting

MembranePotential(~ -70 mV)

Impermeant Ions (~ -

10Mm) phosphates, proteins, nucleic acids

EK = - 85 mV

ECl = - 85 mV

K+

has the GREATESTPERMEABILITYresting potential isNEAREST the E of K

+

Na/K/ATPasePump (~ -5 mV)

electrogenicpump

Gibbs-DonnanEquilibrium

steady-state if BOTHpermeant andimpermeant ions arepresent

NOTES: Resting Membrane Potential is from contribution of:

1. Individual equilibrium potentials ofALL permeant ions MAJOR contributor

CHORD CONDUCTANCE EQUATION: membrane potential is the weighted averageof all equilibrium potentials (only the PERMEANT ions)

2. Na/K/ATPase Pump MINOR contributor (~ -5 mV)

3. Negative Intracellular Substances (Gibbs-Donnan Equilibrium) MINOR contributor (~ -10 mV)

DIGITALIS

the cardiac Na/K/ATPase Na+

accumulates intracellularly with activity of Na/Caexchanger in CELL MEMBRANE Ca

2+sequestered by SR which leads to Ca

2+

released during contraction GREATER CARDIAC CONTRACTION

HYPERKALEMIA and HYPOKALEMIA

HYPERkalemia: outward currentDEPOLARIZES membraneHYPOkalemia: outward current HYPERPOLARIZES membrane


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ACTION POTENTIAL RAPID DEPOLARIZATION followed by SLOWER REPOLARIZATION

Depolarization

potential becomes LESS NEGATIVE (or MOREPOSITIVE)

caused by INWARDCURRENT of Na+

Threshold Potential LEVEL of membrane potential at which action

potential becomes INEVITABLE i.e. there will be anaction potential FOR SURE

Action Potential (Upstroke)

UpstrokerapidINWARDcurrent of Na+

opening of Na+

activation gatesOvershoot

peak of actionpotentialmembranepotential is POSITIVE

Repolarization/ Recovery

slow OUTWARDcurrent of K

+

closing of Na+INactivation gates

opening of K+

channels

closing of Na+ inactivation andopening of K+ are both SLOWERthan activation

Repolarization (Recovery) potential slowly returns to membrane potential

caused by OUTWARDCURRENT of K

+

Undershoot (Hyperpolarizing Afterpotential) potential MORE NEGATIVE than resting

K+

conductance remainshigher than at rest

Properties of Action Potentials1. stereotypical shapeSAME shape throughout length of nerve or muscle

2. self-propagating the action will spontaneously propagate from the site ofcreation

3. all-or none there is no INTERMEDIATE level of action potential4. voltage inactivated persistent depolarization INACTIVATES Na

+channels


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Comparison of Action Potential in different tissues:Nerve andSKELETAL Msc

CARDIAC Msc SMOOTH Msc

ShapeSTEEP

depolarization

STEEP depolarization

then PLATEAU

GRADUAL

depolarization

Cause ofOvershoot

opening ofFAST Na

+ opening ofFAST Na+ and SLOWL-Type Ca

2+

opening ofSLOW L-Type Ca

2+

Cause ofRecovery

closure of FASTNa

+

opening of K+

closure of FAST Na+

and SLOW L-Type Ca2+

opening of K+

closure SLOW L-Type Ca

2+

opening of K+

REFRACTORY PERIODS

ABSOLUTE REFRACTORY PERIOD RELATIVE REFRACTORY PERIODWHOLE of depolarization + FIRST1/3 ofrepolarization

REMAINING 2/3 of repolarization onwards

NO action potential will be generated action potential CAN be generated NEEDS GREATER inward current (greaterstimulus)

ALL Na+

channels closed SOME Na+

channels ALREADY OPEN,BUTK

+conductance is GREATER

ACCOMODATION cell membrane SLOWLY and GRADUALLYdepolarized action potential NOT generated

even if ABOVE threshold potential- voltage-gated Na+ channels become deactivated and the REQUIRED CRITICAL

NUMBER of Na+ channels for depolarization will never be reached

Propagation of Action Potentials through spread of local currents that DEPOLARIZES ADJACENT MEMBRANE if

threshold is reached, a NEW action potential will be created

Action Potential Local Response

LARGER changes in potential SMALLER changes in potential

CONSTANT shape CHANGING shapemagnitude REMAINS CONSTANT evenwith increasing distance

magnitude DECREASES with increasingdistance

SALTATORY conduction ELECTROTONIC conduction

LOCAL RESPONSE refers to the spread of depolarization using LOCAL CURRENTS


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Properties of Action Potential propagation:1. MAINTAINS THE SAME SHAPE: FREQUENCY OF ACTION POTENTIALS (rather than

magnitude) is used to transmit information (think Morse Code)

2. UNIDIRECTIONAL: ONLY forward because the previous membrane is still in itsABSOLUTE REFRACTORY PERIOD

3. SALTATORY: action potential generated only at NODES OF RANVIER (myelininsulates the membrane) action potential JUMPS from 1 node to the next

Speed of Propagation

1. diameter : speed due to resistance2. myelinatin : speed due to length constant

capacitancerestricting generation to nodes

SYNAPTIC AND NEUROMUSCULAR TRANSMISSIONElectrical Synapse Chemical Synapse

Mechanismgap junctions(6 connexIN = 1 connexON)

neurotransmitters

Speed ofTransmission

rapid (no delay)slower (with synaptic delay)mainly from neurotransmitterrelease

Direction of

Transmission

Bidirectional

(if unidirectional = rectification)

UNIdirectional(from pre- to post-synaptic

neuron only)

Where found

hepatocytesmyocardiumintestinal smooth muscleepithelial cells of lens

CNS and PNS

INPUT-OUTPUT RELATIONSInput action potential in PRE-synaptic cellOutput action potential in POST-synaptic cell

One-to-One neuromuscular junction no integration

One-to-Many Renshaw Cells in cord inhibition of motor neuronMany-to-One motor neurons with integration


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Pre-

Synaptic

DEPOLARIZATION of PREsynaptic Neuron Active Zones: areas of pre-synaptic membrane with thesynaptic vesicles

1. opening of voltage-gated Ca+

channels entry of Ca

2+into pre-synaptic terminal

2. neurotransmitter released from pre-

synaptic neuron via exocytosis

Post-Synaptic

NEUROTRANSMITTER IN SYNAPSE

diffuses through the synapse to reach thepost-synaptic neuron (or muscle end-plate)

ACh receptors concentrated atlips of junctional fold

Nerve: Post-Synaptic Potential (PSP)Muscle: End Plate Potential (EPP) From other neurons

EPP and PSP are only LOCAL RESPONSESand are NOT action potentials

PSPEPP

PSPEPP

PSPEPP

PSPEPP

SUMMATION (Spatial and Temporal) THRESHOLD

GENERATION and PROPAGATION of ACTION POTENTIAL

NOTES:

Acetyl CoA +Choline

Ach Acetyl CoA +Choline

Choline

Acetyltransferase

Acetylcholinesterase

- found in the cellmembrane of muscle

Choline: NOT actively synthesized reuptake from ECF (Na+-choline co-transport)

END PLATE POTENTIAL: release of ACh caused by DEPOLARIZATIONMINIATURE END PLATE POTENTIAL: SPONTANEOUS and RANDOM release of ACh

post-synaptic cell membrane does NOT generate action potentials EPP (local responsesonly) spread electrotonically to AXON HILLOCK and INITIAL SEGMENT

AXON HILLOCK part of neuron where axon originatesINITIAL SEGMENT first part of the axon

Lambert-Eaton Myasthenic Syndrome: antibodies vs. Ca2+

channel no release of Ca2+

Myasthenia Gravis: antibodies vs. ACh receptor no stimulation of muscle


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EPSP vs. IPSP types of POST-SYNAPTIC POTENTIALS maybe EXCITATORY or INHIBITORY

EXCITATORY (EPSP) INHIBITORY (IPSP)What it does tothe post-synapticneuron

DEPOLARIZATIONto generation of AP

HYPERPOLARIZATIONto generation of AP

Mechanism

opens Na+

channelsopens K

+channels

- brings membrane potentialhalfway between ENa andEK past threshold

opens Cl-channels

opens K+

channels

- Cl-has a MORE NEGATIVE

E than K+

NeurotransmitterExamples

- GlutamateMAJORexcitatory neurotransmitter

in brain- Acetylcholine (ACh)- Norepinephrine (NE)- Epinephrine (Epi)- Dopamine- Serotonine (5-HT)

- -Aminobutyric Acid(GABA)MAJOR

inhibitory neurotransmitter- Glycine

Types of Summation Summationadditive effect of smaller AP to produce a larger AP

SPATIAL inputs reach post-synaptic neuron AT THE SAME TIMETEMPORAL inputs reach post-synaptic neuron ONE AFTER THE OTHER

Facilitation, Augmentation, Post-Tetanic Stimulation

FacilitationPost-TetanicPotentiation

Long-Term Potentiation

Pre-SynapticREPEATEDstimulation

TETANICstimulation

REPEATED stimulation

Post-Synaptic greater greater Greater

DurationSHORTESTmilliseconds

INTERMEDIATEsecs to minutes

LONGESTdays to weeks

MechanismPRE-SYNAPTIC NEURON neurotransmitter release (2

oto

pre-synaptic Ca2+

)

PRE-SYNAPTIC NEURON neurotransmitter release

POST-SYNAPTIC NEURON sensitivity to neurotransmitter(2

oto NMDA receptor and in

post-synaptic Ca2+

)


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CRITERIA FOR NEUROTRANSMITTERS1. pre-synaptic neuron must produce and store the neurotransmitter2. neurotransmitter must be released by pre-synaptic neuron when stimulated3. application of neurotransmitter to post-synaptic neuron must have the same response as

when stimulating the pre-synaptic neuron4. application of neurotransmitter and pre-synaptic stimulation should be altered the same way

by drugs

Kinds of neurotransmittersNeurotransmitter Precursor Degradation

AcetylcholineAcetyl CoA + CholineCholine Acetyltransferase

Breakdown:Acetylcholinesterase

Reuptake:choline to pre-synaptic neuron

Norepinephrine Tyrosine

L-dopaTyr Hydroxylase

L-Dopa DopaDopa Decarboxylase

Dopa NorepinephrineDopa- -HydroxylaseNorepinephrine EpinephrinePhenylethanolamine-N-

Methyltransferase

Breakdown:Monoamine OxidaseCatechol-O-Methyltransferase

Reuptake:catecholamine to pre-synapticneuron

Epinephrine

Dopamine

Serotonin Tryptophan 5-HT

Histamine Histidine Histamine

Glutamate Glutamate

normal AA metabolismGABAGlutamate GABAGlutamate Decarboxylase

Glycine Glycine

Peptide vs. Non-Peptide NeurotransmittersNON-Peptide Peptide

Producedin nerve terminal as activesubstance

in nerve body (transported by fastaxonal transport) as prehormone

Mechanism small and clear large and electron-dense

Release into the synapse near cell body

Degradation reuptake into pre-synaptic neuron proteolysis of peptide

Duration short latency, short duration long latency, long duration

ExamplesAch, NE, Epi, Dopa, 5-HT VIP, opioids, CCK, Substance P,

TRH


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Notes: Fast Axonal Transport

Kinesin to nerve terminalDynein to nerve body

OpiATE SHOULD be produced from the oppy seed OpiOID NOT produced from poppy but with same effects

Neurotransmitter Release from Pre-Synaptic Neuron: via exocytosisV-SNARE in Vesicle membrane synaptobreVinT-SNARE in Terminal membrane synTaxin and SNAP-25

EXTRACELLULAR REGULATIONEndocrine Neurocrine Paracrine Autocrine

Produced byendocrineglands nerves

DIFFERENTcell type

SAME celltype

Effectdistant (viablood)

local (by diffusion)

Types of Signal Transduction PathwaysIonotropicReceptors

Ionotropic Receptor receptor is an ionchannel

Metabotropic Ion Channel 2n

messenger activates ion channel

SecondMessengers

5 Common Kinds of Second Messengers

cAMPAdenylateCyclase

Protein Kinase A(A for cAMP)

cGMP GuanylateCyclase

Protein Kinase G(G for cGMP)

ITP andDAG

Phospholipase C

ITP: Ca+

in cell(from ER (SR in msc))

DAG: Protein Kinase C

Ca2+

Ca

+ONLY: Ca

+-Calmodulin Protein Kinase

Ca2+

+ DAG: Protein Kinase C (C for Ca2+

)

Tyrosine

Kinases

Receptor Kinase receptor itself is the kinase

Receptor-AssociatedKinase

receptor activates another kinase through theJAK-STAT Pathway (Janus Tyrosine Kinases(JAK) and Signal Transducers and Activators ofTranscription (STAT))


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G-Proteins mediator / interface between second messenger and receptor HETEROTRIMERIC: composed of 3 different subunitsONLY active (A for Active) bound to GTP (has INTRINSIC GTPase activity)

inactive bound to GDPG Protein Effector Hormones/NT

GS (S forStimulate)

MAIN: stimulateAdenylate Cylcase cAMP NE (1,2)and EpiHistamineGlucagonACTH/FSH/LH/TSH

OTHERS: increase Ca2+

influx

Gi (I for Inhibit)Gi1, Gi2, Gi3

MAIN: inhibitAdenylate Cyclase cAMPNE (2 adrenergic)Ach (Muscarinic)OpiatesAngiotensinProstaglandins

OTHERS: activate Phospholipase C and A2 (A2 for

Prostaglandin Synthesis) open K+ channels (MUSCARINIC ACh)

Gt (T is forTransducin)

stimulatecGMP Phosphodiesterase cGMPT1: rodsT2: cones

Golf (OLFaction) stimulateAdenylate Cylcase cAMP different odorants

Gq stimulatePhospholipase C ITP, DAG and Ca2+

Ach (Muscarinic)

NE (1 adrenergic)

CHOLERA

binds to subunit of Gs permanent activation of adenylate cyclase and cAMP opening of Cl

-channel in intestines and WATER LOSS

Down-Regulation and DesensitizationDown-Regulation number of receptors via internalization of receptorsDesensitization sensitivity of receptors via phosphorylation (e.g. -arrestin in b-

adrenergic receptors)


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Kinds of neurotransmittersNeurotransmitters MOA Receptors Where found?

Acetylcholine open Na+ and K+

channels (Na+

> K+)

muscarinicnicotinic

Neuromuscular JunctionALL PRE-ganglionic

POST-ganglionicPARAsympatheticBasal GangliaBetz Cells (Motor Cortex)

C

atecholamine

Norepinephrine varies- and -adrenergic

POST-ganglionic SYMPAthetic

Epinephrine cAMP

Adrenal Medulla (ChromaffinCells)

DopamineD1: Gs, cAMP

D2: Gi, cAMP

D1D2

hypothalamussubstantia nigra

ventral tegmentum

BiogenicAmine

Serotoninbrain stempineal gland (converted tomelatonin)

Histamine hypothalamus

AminoAcids

GlutamateAspartate

AMPA (quisqualate receptor):open Na+ and K+ channels GluIS THEMAJOR

EXCITATORYNEUROTRANSMITTER

throughout the CNS

NMDA: open Ca+, Na

+and K

+

channels

Kainate: similar to AMPA

L-AP4: pre-synatic inhibitor

Metabotropic: IP3 and Ca+

GABA

GABA A:opens Cl

-channels

GABA B: opens K+

channels

GABA AGABA B

MOST COMMONNEUROTRANSMITTER IN THEBRAIN (1/3 of synapses)

basal ganglia

cerebellar Purkinje cellsspinal interneurons

Glycine opens Cl-channels spinal interneurons


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Kinds of neurotransmittersNeurotransmitters MOA Receptors Where found?

Neuropeptides

OpioidsEnkephalinEndorphins

Dynorphine

Endorphin: CNS (pain perceptionpathways)

Enkephalin and Dynorphin:everywhere else

Non-OpioidsSubstance PVIP, Secretin andCCKGlucagonNeurotensin

Substance P: NT of primarysensory neurons

VIP: smooth muscle, glands

CCK: GB contraction

Neurotensin: lowers body temp

PHYSIOLOGY OF THE NERVOUS SYSTEMNeuroglia and their FunctionsNeuroglianeural glue; supportive cells MORE NUMEROUS than neurons (10

13vs. 10

12)

Neuroglia Function

CNS

Astrocytes contribute to blood-brain barrier via foot processes buffer the extracellular environment of neurons forms scars after neural injury

Oligodendroglia form the myelin sheath in the CNS

Microglia phagocytes of the CNS

Ependymal

Cells

epithelium that separates CNS from CSF

produce CSF via choroid plexus

PNS

Schwann Cells form the myelin sheath in the PNS analogous to oligodendroglia in CNS

Satellite Cells cover dorsal root and CN ganglia analogous to astrocytes in CNS

Axonal Transportprovide movement of substances from soma to the axons

FAST Axonal Transport SLOW Axonal Transport

for membrane-bound proteins or organelles for dissolved proteinsFAST: 400 mm/day SLOW: 1 mm/day

ANTEROgrade Axonal Transport from soma to axon via KinesinRETROgrade Axonal Transport from axon to soma via Dynein

Herpes Zoster (Shingles): anterograde transportTetanus Toxin: retrograde transport


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Nervous Tissues Reactions to InjuryDegeneration Regeneration

CHROMATOLYSIS: to NEURON change in staining of the soma 2

oto

protein synthesis staining withbasic aniline dyes

cell swelling eccentric location of nucleus

WALLERIAN DEGENERN: to AXON disintegration of axon DISTAL to

transaction phagocytosis of myelin (EXCEPT

Schwann Cells (PNS) remain viable)

follows the path of Schwann Cells limited by slow axonal transport

ABSENT IN CNSbecauseoligodendrogliadoNOTform a path that growth sprouts cangrow into.

Autonomic Nervous System ALWAYS efferent (i.e. NO SENSORY COMPONENT)

Sympathetic Parasympathetic Somatic

PREganglionicNerve

THORACOLUMBAR Lateral Horn of T1-

12, L1-L3

SHORT nerve

CRANIOSACRAL CN X, IX, VII, III (1973) S2-S4

LONG nerve

NT between PREand POSTganglionic

NICOTINIC AChfor the WHOLE ANS

Autonomic GangliaParavertebral

Sympathetic Trunksnear effector organ

POSTganglionicNerve

LONG nerve (farfrom effector)

SHORT nerve (alreadynear effector)

NT betweenPOSTganglionic andEFFECTOR

NE (ALL and )

MUSCARINIC AChONLY for sweating

MUSCARINIC ACh NICOTINIC

Ach

Effector OrgansSMOOTH and CARDIAC muscleglands

SKELETALmuscle

NOTES: Autonomic Ganglia: refer ONLY to the cell bodies of the POST-synaptic neurons

Adrenal Medulla has NOPOST-ganglionic neurons direct stimulation from PRE-ganglionic neurons (NICOTINIC ACh)EPI 80%NE 20%


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Autonomic NS Receptor Types1 2 1 2

Main Action EXCITE (contractand constrict)

INHIBIT(dilate and relax)

EXCITE (contractand constrict)

INHIBIT(dilate and relax)

Mechanism ITP and Ca + cAMP cAMPWhere found and Actions

Blood Vesselsskin and viscera

VASOCONSTRICT

skeletal muscle

VASODILATE

SphinctersGIT and bladder

CONSTRICT

Smooth Muscle

GIT

MOTILITY SECRETION

GIT, UB and Lungs

RELAX / DILATE

Heart

Myocardium andSA/AV Nodes

HR, contractionand conduction

Other Locations and Actions

Iris

Radial Muscle

PUPILLARYDILATE

MALE GenitalsPresent

EJACULATION

KidneysPresent

RENINFat Cells

Present

LIPOLYSISNOTES: PARAsympathetic is just the OPPOSITE of everything above MUSCARINIC ACh

Nicotinic Muscarinic

ALL post-ganglionic neuronsSKELETAL muscle

(RECALL:ACh is NTbetweenpre- andpost-ganglionic neurons post-ganglionicneurons must have receptors for ACh)

SMOOTH and CARDIAC muscleglands

ALWAYS excitatory EXCITATORY: smooth msc and glandsINHIBITORY: heart

IONOTROPIC receptor EXCITATORY: ITP and Ca+

INHIBITORY: cAMP open of K+

chan.


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SWEATING IS SYMPATHETIC BUT MEDIATED BY MUSCARINIC ACh!

AUTONOMIC CENTERS IN BRAIN

Medulla

vasomotor center

breathing center controls RRswallowing, coughing, vomiting centers

Ponspneumotaxic center controls depth ofbreathing

Midbrain micturition center

Hypothalamusthirst and hunger centerstemperature center

SENSORY NERVOUS SYSTEM

Sensory Receptors transducer environmental signal to action potentialReceptive Field area of body that changes the firing rate of a sensory

neuron when stimulated

Classification of Sensory ReceptorsSpecial Superficial Deep Visceral

VisionAuditionOlfactionTaste

Balance

TouchPressureVibrationTemperature

Pain

DEEP pressureDEEP painProprioception

DistentionHungerVisceral Pain

Kinds of Nerve FibersGENERALFiber

MOTOR fibersSENSORY Fiber Myelination Diameter Velocity

A : motoneuronsto muscle

Ia: muscle spindleMyelinated Largest Fastest

Ib: Golgi tendon organ

II: muscle spindle

Myelinated Medium Medium: vibration (Paccinian) andtouch

: motoneuronsto spindles Myelinated Medium Medium III: pressure and pain

Myelinated Small Medium: touch, FAST pain andtemp

B PREganglionic autonomic Myelinated Small Medium

C IV:SLOW pain and tempNOTmyelinated

Smallest Slowest


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Adaptation of Sensory ReceptorsSlowly Adapting Rapidly Adapting

a.k.a. tonic phasic (PHAS forFASt)

StimuliDetected

respond to prolonged stimulirespond to changes in firingfrequency

STEADY stimuli CHANGING stimuli (on-off)

ExamplesPressure (Ruffinis Corpuscle)SLOW Pain

vibration (Paccinian Corpuscle)light touch

Steps in Sensory TransductionNeuron Locn of Cell Body

1st

ORDERDorsal RootCord Ganglia

sensory receptor receives stimulus

receptors may be epithelial cells or primary afferentneurons

ion channels opened DEPOLARIZATION(Receptor/Generator Potential) of sensory receptor

EXCEPTIONSare the rods and cones which areHYPERPOLARIZED

threshold potential reached action potential

generated

2nd

ORDERSpinal CordBrainstem

AP transmitted to 2nd

order neurons

3rd

ORDER Thalamusthalamus receives ALL sensory input for relaying tothe cortex

4th

ORDERSensory Cortex(Parietal)

conscious perception of stimulus

NOTES: CROSSING OVER at level of 2

NDORDER NEURON

THRESHOLD STIMULUS: WEAKEST stimulus that can be reliably detected


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SOMATOSENSORY SYSTEMPathways of Touch, Movement, Temp and Pain

Dorsal Column Spinothalamic (Anterolateral)

Modalities

FINE touchPressureVibrationProprioception2-Point Discrimination

LIGHT touchPainTemperature

Receptors

Paccinian vibration phasic

FREE NERVE ENDINGSMeissner flutter phasic

Ruffinis pressure tonic

Merkels Disc location tonic

Nerve TypesGroup A- fibers myelinated, large diameter fast

conduction

Group III (Group A-) fibers myelinated, medium diameter

FAST conduction

Group IV (Group C) fibers unmyelinated, small diameter

SLOW conduction

1st

OrderNeuron

DORSAL ROOT GANGLIONtravels up the Dorsal Funiculus of thespinal cord to medulla

PRIMARY AFFERENT FIBERSsynapses at the SPINAL CORDalready

2

nd

OrderNeuron

Medulla

Nucleus Cuneatus and NucleusGracilisMedial Lemniscus tothalamus

ANTEROLATERAL SPINAL CORD

ascends to the ventral part of LateralFuniculus to thalamus

3rd

OrderNeuron

THALAMUS1. CORD: Ventral Posterior Lateral

(VPL) nucleus

THALAMUS1. Ventral Posterior Lateral (VPL)

nucleus2. Intralaminar Complex

4th

OrderNeuron

SOMATOSENSORY CORTEXSI: PRIMARY Somatosensory Cortex post-central gyrusSII: SECONDARY Somatosensory Cortex superior bank of lateral fissure

NOTE:forSpinothalamic Pathway:projection toCingulate GyrusandInsula(Limbic System)

NOTES: SUBSTANCE P: neurotransmitter for pain


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Comparison of Cutaneous Receptors

Paccinian Meissner Ruffini Merkel

Adaptation Phasic Tonic

Modality vibration velocity pressure locationStructure /Location

onion-shaped,subcutaneous

in GLABROUS(non-hairy) skin

encapsulatedin epithelialcells

ReceptiveField

HIGH frequencyarea

LOW frequencypunctate

stretching punctuate

AXON REFLEXANTIDROMAL spread of action potential (towards site of stimulus) release ofSUBSTANCE P and CALCITONIN-GENE RELATED PEPTIDE (CGRP) inflammation

Somatosensory Homunculus

LOWER EXTREMITY medial surfaceUPPER EXTREMITY dorsolateral surfaceFACE above lateral fissureHEAD upper and lower extremityABDOMINAL superior banks of lateral fissure

NOTE difference between HEAD and FACE

FACE: Trigeminal Nerve

1st

Order NeuronPrimary Afferent Neuron travels through CN V to the trigeminal ganglion

2nd

Order Neuron

Trigeminal Ganglion

travels through the Trigeminothalamic Tract to thethalamus

3rd

Order NeuronThalamus Ventral Posterior MEDIAL (VPM) Nucleus

4 Order Neuron Somatosensory Cortex

Effects of Pathway Interruptions

Dorsal Cord Graphesthesia and Astereognosia in IPSILATERAL side

Ventral CordSensory and Affective components of Pain inCONTRALATERAL side

VPL and VPM

Nuclei

ALL sensation from CONTRALATERAL side of body

EXCEPT AFFECTIVE component of painSomatosensoryCortex

ALL sensation from CONTRALATERAL side of body,following the homunculus

ParietalAssociationCortex

CONTRALATERAL findings of the ff:1. neglect2. constructional apraxia3. dressing apraxia


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SPECIAL SENSESTEN Layers of the Retina

Pigment CellsPigmentedRetinal Layer

11-cis-retinalall-trans-retinal via LIGHT(photoisomerization) Metarhodopsin II

VITAMIN A: necessary for regenerationof 11-cis-retinal

Rods and ConesPhotoreceptorLayer

1. Metarhodopsin II Gt (transducin)T1: rods; T2: cones

2. cGMP Phosphodiesterase cGMP3. CLOSURE of Na

+channels

4. HYPERPOLARIZATIONneurotransmitter release

External LimitingMembrane

NUCLEI of rods/conesOuter NuclearLayer

AXONS of Rods/Cones +AXONS of Bipolar Cells

Horizontal Cells

Outer PlexiformLayer

NUCLEI of Bipolar CellsInner NuclearLayer

If NT from rods/cones is:- Excitatory:HYPERpolarization of bipolar- Inhibitory:DEpolarization of bipolar

AXONS of Bipolar Cells +AXONS of Ganglion Cells

Amacrine Cells

Innter PlexiformLayer

1. CENTER of receptive field: receptor toganglion DIRECTLY

2. SURROUND of receptive field: receptorto ganglion via HORIZONTAL CELLS

- usually ON-CENTER, OFF-SURROUND

NUCLEI of Ganglion CellsGanglion CellLayer

OUTPUT cells of the retina

AXONS of Ganglion CellsOptic NerveLayer


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Internal LimitingMembrane

Projections of Mller Cells

Optic PathwaysComposed of: LESION

Optic Nerve L and R Optic NervesMONOCULARblindness, NOmacular sparing

Optic Chiasm crossover of L and R NASAL retinaBitemporalHemianopsia

Optic TractRIGHT from R TEMPORAL + L NASAL

CONTRALATERAL Homonymous

Hemianopsia

LEFT from L TEMPORAL + R NASAL

LATERAL Geniculate Body(analogoustothalamus

RIGHT from R Optic Tract

LEFT from L Optic Tract

Geniculocalcarine Tract(Optic Radiation)

Temporal(Meyers Loop)

LOWER hemiretinaCONTRALATERAL HomonymousHemianopsia, WITHmacular sparing

Parietal UPPER hemiretina

Visual Cortex

(Layer 4 of Striate Cortex)

banks of the CALCARINE FISSURE CONTRALATERAL Homonymous

Hemi- orQuadrantanopsia,WITHsparing

LINGUAL GYRUS

ventral to fissure

LOWER hemiretina

CUNEUSdorsal to fissure

UPPER hemiretina

NOTES: Rods vs. Cones

Rods Cones

G-Protein T1 T2

Synapse with Bipolar MANY-to-one FEW-to-one

Amount of photopigment MANY LESS

Acuity low high

Sensitivity High lowLight Adaptationreduction in rhodopsin

worse better

Night Adaptationregeneration of rhodopsin

adapts LATER adapts EARLY

Day or Night? NIGHT vision (scotopic) DAY vision (photopic)

Presence in Fovea absent present (for acuity)

Color Vision NO YES


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Cells in the Visual CortexSIMPLE bars of light with correct orientation and positionCOMPLEX MOVING bars of lightHYPERCOMPLEX curves and angles

Chemical Reactions of VisionLIGHT

opsin + 11-cis-retinal rhodopsin all-trans-retinal + opsin retinol

PURPLE WHITEopsin released afterisomerisation to all-trans retinal

COLOR VISION:Trichromacy Theory

- absorption best at RED, GREEN and BLUE (RGB) color results from differentcombinations of RGB

- color results from differences in WAVELENGTH, but NOT in INTENSITY

TRICHROMAT ALL 3 colors PRESENT, NORMALMONOCHROMAT ALL 3 colors ABSENT

DICHROMAT ONLY 2 colors present, loss of 1 colorProtanopia loss of red (longest )

Deuteranopia loss of green (medium)

Tritanopia loss of blue (shortest )

Pupillary Light Reflex

Retina Pretectum EDINGER-WESTPHAL NUCLEUS dilator

Interconnectionbetween L & R

PARAsympathetic

Direct Reflex ipsilateral eyeConsensual Reflex contralateral eye

Errors of RefractionEmmetropia NORMALHypertropia far-sighted, focus BEHIND retina correct with CONVEX lens

Myopia near-sighted, focus IN FRONT of retina correct with CONCAVE lensPresbyopia loss of accommodation correct with CONVEX lensAstigmatism non-uniform curvature of lens correct with CYLINDER

Refractive Powermeasured in diopters = reciprocal of FOCAL LENGTH (in meters) NORMAL


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Pupillary Dilator opens iris activated by Sympathetic (1)Pupillary Sphincter closes iris activated by Parasympathetic (CN III)

Ciliary Muscle (activated by Parasympathetic CN III)

CONTRACTED LAX suspensory ligaments (zonula fibers) FLAT lensRELAXED TENSE suspensory ligaments (zonula fibers) CURVED lens

Auditory and Vestibular SystemsParts of the EarPart Components Notes

Outer Earpinnaexternal auditory canal

directs sound waves to middle ear

Middle Ear

tympanic membrane

ossicles (malleus, incus, stapes)

Tensor Tympani:CN V, attached to malleus

Stapedius:CN VII, attached to incus

transmits sound waves to inner ear

AIR-filled

SOUND tympanic membranemalleusincus stapes OVAL window

tensor tympani and stapedius causedampening of sound

Inner Ear

BONY MEMBRANOUS organ of hearing (Organ of Corti, located inthe Scala Media on top of Basilar Membrane)FLUID-filled

PERIlympharound ducts(peri)

like ECF Na+, K+

ENDOlymphinside ducts(endo

like ICF Na

+, K

+

Borders of Scala Media1.Reissners Membrane: border with Scala

Vestibuli2.Basilar Membrane: border with Scala

Tympani3.Stria Vascularis: produces endolymph

Components of Organ of Corti1.Outer Hair Cells: PLENTY (3 rows)2.Inner Hair Cells: FEW (1 row only)3.Stereocilia: non-motile cilia on apex of hair

cells4.Tectorial Membrane: gelatinous membrane

on top of hair cells

Scala VestibuliScala TympaniVestibleSemicircularCanals

Scala MediaSemicircular

DuctsUtricleSaccule


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Auditory PathwayNotes

Outer Ear

Tympanic Membrane

Malleus

Incus

Stapes

Amplification of Sound (IMPEDANCE MATCHING)1. mechanical advantage of lever action of malleus and stapes

(malleus has a LONGER lever arm vs. stapes)2. concentration of waves on OVAL window (tympanic membrane is

LARGER than oval window)

OVAL Window

PERILYMPH

sound waves transmitted to perilymph

Cochlea: composed of 2 turnsHelicotrema: apex of cochlea, junction of vestibuli and tympaniOval and Round Windows: base of cochlea

Scala VESTIBULI

helicotrema

Scala TYMPANI

ROUND window

Scala MEDIAOrgan of Corti

Inner Hair Cells:MAJORITY of neuralinformation (~90%)

Outer Hair Cells: MINORcontribution (~10%)

waves in perilymph displace the basilar membrane creates

shearing force BENDING OF HAIR CELLS

BENDING causes changes in K+

conductancebend TOWARDS tallest cilium: DEPOLARIZED(Cochlear

Microphonic Potential (CMP)) release of EXCITATORYNT(Glu or Asp)

bend AWAY FROM tallest cilium: HYPERPOLARIZE

BASE: narrow, stiffHIGH-frequency soundAPEX: wide, loose LOW-frequency sound

Spiral Ganglion 1

s

ORDER NEURONS: nuclei of hair cells

Cochlear Division of CNVIII

Dorsal and VentralCochlear Nuclei

2n

ORDER NEURONS: there could be some crossing-over therefore, central lesions RARELY cause UNILATERAL deafness


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Lateral Lemniscus MAIN ascending auditory tract

Inferior Colliculus

Medial Geniculate Body 3

rORDER NEURONS: analogous to the thalamus

Auditory Radiation

Auditory Cortex

Transverse TemporalGyri of the TemporalLobe

Tonotopic Map: localization of frequencies in the auditory cortex

Main Functions:1. tone discrimination2. sound localization

- differences in time of sound arrival on both sides- differences in sound intensity on both sides

NOTES: Frequency in hertz (Hz)

Intensity in decibles (dB)

rP

Plog20SPL where P is measured sound pressure and Pr is a reference pressure

(0.0002 dyne/cm2

= absolute threshold for human hearing)

Binaural Receptive Fields: neurons above cochlear nuclei respond to stimulation to EITHEREAR 2

oto crossing over of fibers

Lesions to Auditory Pathway

Part DeafnessFrequencyDiscrimination

SoundLocalization

ToneDiscrimination

Ear to CochlearGanglion

UNILATERAL reduced no effect no effect

Lateral Lemniscus toCortex

LITTLE effect no effect reduced reduced


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Vestibular PathwaySemicircular Canals

1. Horizontal2. Superior3. Posterior

ANGULAR acceleration(rotation)

lead to adjustments in the head,eye and postural muscles:1. maintain stable visual image2. maintain balance

Utricle: horizontalSaccule: vertical

LINEAR acceleration(forward/backward/up/down)

ANGULAR ACCELERATION LINEAR ACCELERATION

Organs

Involved

Crista Ampullaris (Ampullary Crest)- located in ampulla at base of

semicircular ducts

Macula Utriculi (in Utricle)Macula Sacculi (in Saccule)

Hair Cells- single Kinocilium- multiple Stereocilia

Cupula- gelatinous membrane ONLY- SAME spec grav as endolymph

Otolith Membrane- gelatinous membrane + CaCO3- GREATER spec grav as endolymph

Generation ofAction Potential

due BENDING of hair cells:

bend TOWARDS kinocilium: DEPOLARIZED release of EXCITATORYNT(Glu or Asp)

bend AWAY FROM kinocilium: HYPERPOLARIZE

ON HEAD TURNING

A. START of turn: endolymph left behindhair cells on side IPSILATERAL to direction of turn: DEPOLARIZEDhair cells on side CONTRALATERAL to direction turn: HYPERPOLARIZED

B. END of turn: endolymph catches uphair cells on side IPSILATERAL to direction of turn: HYPERPOLARIZEDhair cells on side CONTRALATERAL to direction turn: DEPOLARIZED


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Crista Ampullarisin semicircular DUCT

Scarpas Ganglion 1s

ORDER NEURONS: nuclei of hair cells

Vestibular Branch of CN

VIII

Vestibular Nuclei2

nORDER NEURONS: located in the rostral medulla and caudal

pons

Various Projections

Medial Longitudinal Fasciculus (MLF)(Oculomotor Nuclei)

Vestibulo-Ocular Reflex

Lateral Vestibulospinal Tract(POSTURAL muscles)

Vestibulo-Collic ReflexMedial Vestibulospinal Tract(NECKmuscles)

Thalamus then to Cortex conscious sensation

Cerebellum

Reticular Formation

Contralateral Vestibular Complex


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Olfactory PathwayNotes

Olfactory Mucosa(Olfactory Epithelium)

1s

ORDER NEURONS

odorant molecules dissolved in mucus layer activate olfactorychemoreceptors in cilia of the neurons activate Golf that cAMP open cAMP-dependentNa

+channels

DEPOLARIZATION

- receptor cells are TRUE neurons- short half-life (60 days) continuously regenerated from basal

stem cells olfactory neurons are the ONLY neurons capableof regenerating

Olfactory Nerve (CN I)

unmyelinated C fibers small and SLOW

TRIGEMINAL NERVE (CN V): for painful and noxious stimuli

Cribriform Plate

Olfactory Bulb

2n

ORDER NEURONS

Mitral and Tufted Cells: 2nd

Order NeuronsInterneurons (Granule Cells and Periglomerular Cells)

MANY-to-one pattern

Olfactory Tract

Anterior Olfactory Nucleus: contains neurons that project toCONTRALATERAL bulb via the anterior commissure

divides into Lateral and Medial Olfactory StriaeLATERAL prepiriform cortexMEDIAL amygdale and basal forebrain

Prepiriform Cortex

(Olfactory Cortex)

Amygdaloid Nucleusand Basal Forebrain

Quality

combnatn of stimulifrom different chemoreceptors

Intensity overall amount ofneural activity

6 Primary Qualities of Odor

1. floral: rose2. ethereal: pear3. musky: musk4. camphor: eucalyptus5. putrid: rotten eggs6. pungent: vinegar


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Taste PathwayNotes

Taste Chemoreceptorslocated intaste buds

taste chemoreceptors are NOT the 1o

afferent neurons (UNLIKEolfactory chemoreceptors)

Papilla: projections in tongue that contain taste budsAnterior and lateral 2/3: foliate and fungiform papillaePosterior 1/3:circumvallate papillae

Taste Bud: receptors (50-150) + supporting cells + basal cells

- short half-life (10 days) regenerated from basal cells

Chorda Tympani(CN VII)

Glosspharyngeal Nerve(CN IX)

Vagus Nerve(CN X)

anterior 2/3 of tongue posterior 1/3 of tongueback of throat

larynx and epiglottisupper esophagus

1st

ORDER NEURONS

Geniculate Ganglion Petrosal Ganglion Nodose Ganglion

EFFERENT THEN ENTER THE MEDULA

Solitary Tract pathway REMAINS UNCROSSED until the cortex

Solitary Nucleus 2nd

ORDER NEURONS

Ventroposteromedial(VPM) Nucleus of

Thalamus3

rdORDER NEURONS

Gustatory Areas

1. FACEarea ofS12. Insula

Qualitycombnatn of stimulifrom different chemoreceptors

Intensity overall amount ofneural activity

4 Primary Qualities of Taste

1. salty: NaCl

2. sweet: sugar3. sour: HCl4. bitter: quinine


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MOTOR SYSTEMMotor Unit

-motoneuron + muscle fibers = motor unit

SINGLE

Small Large

few msc fibers many msc fibers

threshold firefirst

threshold firelast

small force large force

VARIABLE

Fine Control: FEW fibersLarge Movements:MANYfibers

NOTES: MOTOR UNIT: same neuron, different muscle fibers

MOTONEURON POOL: same muscle group, different neurons

SIZE PRINCIPLE: force of contraction due to the number of motoneurons recruited

Muscle Sensory System

Muscle Spindles Golgi TendonPaccinianCorpuscles

Nociceptors

Info Provided muscle LENGTH muscle TENSIONvibration (highfrequency)

painstimulated by length tension

inhibited by length tension

Location PARALLEL toextrafusals

IN SERIES withextrafusals

embedded insuibcutaneous

free nerve endings

SensoryInnervation

Group Ia fibersGroup II fibers

Group Ib fibers Group II (A-)fibers

Group III: fast painGroup IV: slow pain

MotorInnervation

-motoneurons

Muscle Motor System

EXTRAfusal fibersINTRAfusal fibers

Nuclear Bag Nuclear Chain

Location andMorphology

big fibersbulk of the muscle

PARALLEL to EXTRAfusal fibers

nuclei in a central bag nuclei in a chain

FunctionPRIMARILY MOTOR PRIMARILY SENSORY

generate forcedetect changes inDYNAMIClength detect changes inSTATIClength

SensoryInnervation

Paccinian CorpusclesNociceptors

Group Ia Fibers Group II Fibers

MotorInnervation

-motoneurons -motoneurons to adjust sensitivity of musclespindles


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MUSCLE REFLEX SYSTEMSSTRETCH(MYOTATIC) REFLEX

GOLGI TENDONREFLEX

FLEXORWITHDRAWAL

NUMBER OFSYNAPSES MONOsynaptic DIsynaptic POLYsynaptic

EXAMPLE Knee-Jerk Reflex Clasp-Knife Reflexwithdrawal from a hot

stove

Afferent Arm

Muscle Spindles(Intrafusal fibes)

Golgi Tendon OrganPain Afferents (Free

Nerve Endings)Stimulated: length Stimulated: tension

Inhibited: length Inhibited: tension

Group Ia and II fibers Group Ib fibers Group III and IV fibers

Interneurons NONEINHIBITORY

INTERNEURONMANY

INTERNEURONS

Efferent Arm -motoneuron -motoneuron -motoneuron

EffectAGONIST: contractANTAGONIST: relax

SYNERGIST: activate

AGONIST: relaxANTAGONIST: contract

IPSILATERAL: FlexionFlexors: contractExtensors: relax

CONTRALATERAL:

ExtensionFlexors: relaxExtensors: contract

return muscle tooriginal length

reduce tension inmuscle

IPSILATERAL: moveaway from stimuli

CONTRALATERAL:maintain balance


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Motor Centers and Pathways Pyramidal pass through the medullary PYRAMIDS\

EXTRApyramidal everything else

Originates in Projects to Functions

Pyramidal

CorticospinalTract Primary Motor

Cortex (PrecentralGyrus, Area 6)

Spinal Cord

-motoneuronsvoluntary control of muscles ofthe extremities

CorticobulbarTract

Brain Stem-motoneurons

voluntary control of muscles ofthe head/face

Extrapyramidal

RubrospinalTract

Red NuclesLATERAL spinalcord

control of EXTREMITIES

FLEXORS: Activate

EXTENSORS: InhibitLateralVestibulospinalTract

Deiters NucleusIPSILATERALmoto- andinterneurons

control of TRUNK muscles

FLEXORS: InhibitEXTENSORS: Activate

PontineReticulospinalTract

Pontine ReticularFormation

VENTROMEDIALspinal cord


FLEXORS ANDEXTENSORS: Activate

Extensors > Flexors

MedullaryReticulospinalTract

Medullary ReticularFormation

IntermediateGray Area


FLEXORS ANDEXTENSORS: Inhibit

Extensors > Flexors

TectospinalTract

Superior ColliculusCERVICALspinal cord

control of NECK muscles

NOTES: CORD TRANSECTIONS

above REDNUCLEUS

Function: activation of extremity FLEXORSloss of inhibition Decorticate Rigidity

above PONTINE

RETICULOSPINAL

Function: activation of trunk FLEXORS AND EXTENSORS

(but extensors > flexors)loss of inhibition Decerebrate Rigidity

above LATERALVESTIBULOSPINAL

Function: activation of trunk EXTENSORSloss of inhibition Decerebrate Rigidity

C1 DEATH

C3 innervations to diaphragm apnea

C7 sympathetic tone to heart bradycardia + hypotension


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SPINAL SHOCK: loss of excitatory input from BOTH - and -motoneurons FLACCIDITY(-motoneuron) and AREFLEXIA (both - and -motoneuron)

MOTOR CORTICES

Premotor + Supplementary Motor Area 6 planning of movementPrimary Motor Area 4 execution of movement

CEREBELLUM3 FUNCTIONAL PARTS OF THE CEREBELLUM

VESTIBULO cerebellum from the vestibular system for balance /eye movement

PONTO cerebellumfrom the motor cortex viapons

. for planning and initiation ofmovement

SPINO cerebellum from the spinefor control of rate, force,range and direction of

movement (synergy)

Flow of Information in the CerebellumINPUT INTEGRATION OUTPUT

Climbing Fibersfrom theINFERIOR OLIVEONLY

Pukinje Cells- multiple synpses,

COMPLEX spikes- conditioning of the Purkinje

fibers, motor learning

PURKINJE CELLS- the ONLY output cells

of the cerebellum- INHIBITORY: uses

GABA

Projections:1. Deep Cerebellar Nuclei2. Vestibular Nuclei

Mossy FibersfromMANYsources

Purkinje Cells- multiple synpses, SIMPLE

spikes

excite

Granular Cells (located inglomeruli)

excite

INHBITORY NEURONS

Basket and Stellate CellsGolgi Type II Cells


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Layers of the Cerebellum innermost outermost

Granular Purkinje Molecular

Cells

3 Gs

1. Golgi Type II2. Granular in (Glomeruli)

Purkinje

Neither G nor PurkinG

1. Basket2. Stellate

Neurites1. dendrites of Purkinje2. axons of granule cells

parallel fibers

BASAL GANGLIA modulates thalamic outflow to cortex to plan and execute SMOOTH movements 4 Parts:

1. Globus Pallidus: receives INPUT from cortex2. Striatum: sends out OUTPUT to cortex and thalamus3. Substantia Nigra4. Subthalamic Nuclei

Pathways of the Basal Ganglia from striatum to cortex

PathwayEffect ofPathway

DopamineReceptor

Effect of Dopamine on Pathway

INDIRECT INHIBITORY D2 inhibitory

inhibitory on inhibitory

(disinhibition) EXCITATORYDIRECT EXCITATORY D1 excitatory excitatory on excitatory

Lesions of the Basal Ganglia1. Globus Pallidus: loss of posture2. Subthalamic Nucleus: disinhibition of CONTRALATERAL side3. Striatum: loss of inhibition (Recall: output of striatum is INHIBITORY)4. Substantia Nigra:Parkinsons Disease (2

oto Dopaminergic neurons lead-pipe rigidity,

tremor, bradykinesia)

HIGHER CORTICAL FUNCTIONSSleep and EEG

Alert, ACTIVE -wavesAlert, RELAXED -wavesSleep SLOW waves


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REM (Rapid Eye Movement)

EEG Pattern S/Sxsoft body, hard dick, fast and small eyes

similar to:

1. AWAKE state2. STAGE 1 Non-REM sleep

- RAPID EYE MOVEMENT ( REM sleep)

- dreams- loss of muscle tone (FLACCIDITY)- pupillary CONSTRICTION- penile ERECTION

Language

RIGHT HemisphereLEFT Hemisphere(L for Language)

NON-VERBAL Language- facial expression- body language- intonation

Spatial Tasks

communicate

viaCORPUSCALLOSUM

VERBAL Language- expressive language

- receptive language(comprehension)

Aphasias damage to the LEFT hemisphere language centers

Speaking Comprehension RESULT

Wernickes

(Receptive)

Wernickes

Area

intact impaired word salad

Brocas(Expressive)

BrocasArea

Impaired intact no output

Temperature Regulation ANTERIOR Hypothalamus compares MEASURED CORE BODY TEMP to SET POINT

TEMP

FEVER- pyrogensINCREASE the set-point hypothalamus perceives core body temp as LESS

than set-point mechanisms INCREASES core body temp- pyrogens IL-1 PG (prostaglandins in hypothalamus set-point)

Heat Stroke: temp causes tissue damageHypothermia: heat generating mechanism cant compensate for tempMalignant Hyperthermia: 2

oto inhaled anesthetics oxidative phosphorylation and heat

production in skeletal muscle


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Notes

Anterior HypothalamusONLY the ANTERIOR hypothalamus can compare set-point withcore body temp

CORE > SET-POINTbody is HOTTER

CORE < SET-POINTbody is HOTTER

ANTERIOR Hypothalamus POSTERIOR Hypothalamus

LOSE HEAT GENERATE HEAT

1. RADIATION and CONVECTION

- cutaneous blood flow (1SYMPATHETIC)

2. EVAPORATION

- sweating (Mus ACh SYMPATHETIC)

1. metabolism thyroid hormones to metabolic rate and heat production

2. lipolysis (BROWN fat)1SYMPATHETIC

3. shiveringMOST POTENTMECHANISM TO

HEAT,

heatproduction by skeletal muscle

RETURN OF CORE TEMP TO SET-POINT

CEREBROSPINAL FLUID (CSF) PHYSIOLOGYNotes:

VENTRICULAR

CHOROID PLEXUS

site of production of CSF located in 2 LATERAL VENTRICLES, 3

rd

VENTRICLE and 4th

VENTRICLE

INDEPENDENT of:a. pressure in ventriclesb. systemic BP

Lateral Vent 1 per hemisphere

Foramen ofMonro

connect lateral vent with3

rdvent

3r

Vent Diencephalon

Aqueduct ofSylvius

Midbrain, connect 3r

vent with 4

thvent

4th

Vent Pons and Medulla

SUBARACHNOID

enters the SUBARACHNOID SPACE throughforamina in the ROOF OF THE 4

thVENT

1 MEDIAL: Magendie (M for Medial)2 LATERAL: Luschka (L for Lateral)

absorption in the SUBARACHNOID VILLIABSORPTION: CSF pressure : absorption(unlike production)

dural venous sinuses systemic circulation


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NOTES: CSF vs. Blood

CSF Na+

and Cl-, equal HCO3

- NaCl to MAINTAIN EQUAL OSMOLARITY

Mg2+

, Crea Glc, CHON, cholesterol, Ca

2+, K

+

High in CREAM, Low SUGAR, CHONCHOLate, CAKe

High in CREA, MgLow in sugar (glucose), CHON, CHOLesterol, Ca

2+, K

+

BLOOD-BRAIN BARRIER (BBB)

Astrocyte Foot Processes + Capillary EndotheliumIMPERMEABLELipid Soluble (non-polar, CO2, O2, H2O): permeable to BBBWater Soluble (polar):NON-permeable to BBB, needs transpoters

Choroid PlexusPERMEABLE area for secretion of substances into the CSF

Functions of the BBB1. maintains environment surrounding neurons CSF is ESSENTIALLY THE SAME as the

ECF of neurons2. prevents escape of neurotransmitters

PHYSIOLOGY OF THE CARDIOVASCULAR SYSTEMHemodynamicsVelocity of Blood Flow

AQVelocity Determinants of Velocity1. Q: amount of blood flow (Cardiac Output)

2. A: total cross-sectional area

blood is SLOWEST at capillaries LARGEST TOTAL areablood is FASTEST at aortaSMALLEST TOTAL area

Quantity of Blood Flow (Cardiac Output)

R

P)CO(Q

Determinants of Cardiac Output

1. P: pressure gradient DRIVER OF FLOW (analogous to voltage)2. R: total peripheral resistance

HINDRANCE TO FLOW (analogousto resistace in electric circuits)

P = MAP RA pressure, where MAP =3

SBPDBP2

Assuming constant Q, if R, there is also in P cause of theGREATEST DROP IN PRESSURE IN THE ARTERIOLES


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Resistance

4r

L8R

Determinants of Resistance

1. : viscosity of blood resistance if with anemia, Hct2. L: length of the vessel

3. r: radius of the vessel

resistance is GREATEST at the arterioles contraction of muscularwall can radius of the vessel

Resistance in Parallel

n21total R

1

R

1

R

1

R

1

TOTAL R < INDIVIDUAL R TOTAL resistance decreases

when there is a branch in anartery

Resistance in Series

Rtotal = R1 + R2 + ... + Rn

TOTAL R > INDIVIDUAL R GREATEST CONTRIBUTOR

to total resistance is theresisatance in the arterioles

Capacitance and ElastanceCapacitance: change in volume per change in pressure measure of DISTENSIBILITYElastance: change in pressure per change in volume measure of RIGIDITY

Capacitance Elastance Determinants of Capacitance and Elastance

PVC

VPE 1. V: change in volume2. P: change in pressure

veins have capacitance they contain a lot ofblood at low pressures (MOST OF THE BLOOD)

Reynolds NumberThe HIGHER THE NUMBER, the HIGHER THE TURBULENCE

Factors affecting Turbulence:1. velocity of flow

2. viscosity


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HEART (LEFT VENTRICLE)

Aorta RESISTANCEVESSELS

THICK walls smooth muscle elastic tissue

HIGH PRESSURE

LOW VOLUME(stressed volume)

Arteries

Arterioles highest RESISTANCE

Capillarieslargest TOTALCROSS-SECTIONALAREA

EXCHANGE OFSUBSTANCES

THINNEST walls(single layer ofepithelium + BM)

Venules

CAPACITANCEVESSELS

THIN walls smooth muscle elastic tissue

LOW PRESSUREHIGH VOLUME(unstressed volume)

Veins

highestCAPACITANCE (containsmost of the blood in thebody)

Vena Cava

HEART (RIGHT ATRIUM)

NOTES:

vessels in SKIN and VISCERA 1-adrenergic receptor CONSTRICTIONvessels in SKELETAL MUSCLES 2-adrenergic receptor DILATATION

Mean PressuresAorta 100 mmHgArterioles 50 mmHg (1/2 of Aorta)Capillaries 20 mmHg (1/5 of Aorta)Vena Cava 4 mmHg (1/25 of Aorta)

Blood Pressures

SBP HIGHEST BP after contraction (systole)DBP LOWEST BP during relaxation (diastole)

Pulse Pressure = SBP - DBP MOST IMPORTANT determinant is STROKE VOLUME


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Electrophysiology of the HeartParts of the ECG

P WaveDEPOLARIZATION of BOTH L and R ATRIA depolarization ONLY, repolarization not seen BURIED in the QRS

complex

PR Intervalfrom the BEGINNING of P to BEGINNING of QRS indicates conduction through the AV node prolonged PR if with

an AV block

QRS Complex DEPOLARIZATION of VENTRICLES

ST Segmentfrom END of S to BEGINNING of T indicates period when the ventricle is still depolarized

QT Intervalfrom BEGINING of QRS to END of T indicates WHOLE period of ventricular depolarization-

repolarization

T Wave REPOLARIZATION of VENTRICLES

Automaticity and Conduction Velocity

AUTOMATICITY CONDUCTION VELOCITY

Definitionability to spontaneously generateaction potentials

time required for excitation to spread

Main Determinant

RATE of slow depolarization inPhase 4 reflects the RATE of the slow

inward Na+

current (If) duringPhase 4

MAGNITUDE of depolarization inPhase 0 reflects SIZE of inward current

(Na+

for conducting ells, Ca2+

forautomatic cells)

Autonomic Effect

CHRONOTROPY: changes in theHEART RATE

positive: HRnegative: HR

DROMOTROPY: changes in theCONDUCTION VELOCITY

positive: velocity, PRnegative: velocity, PR

(NOTE:dromotropy usually refers toconduction through AV Node)

Regulators andMechanism

POSITIVE NEGATIVE POSITIVE NEGATIVE

1Adrenergic: rate of If

MUSACh: rate of If

1Adrenergic: size of inward

Ca2+ current

MUS ACh size of inward

Ca2+ current

Notes: Intrinsic Firing Rates

SA Node (60-100 bpm) > AV Node (40-60 bpm) > His-Purkinje (20-40 bpm)

Conduction VelocitiesFASTEST His-Purkinje System to allow for efficient ventricular contractionSLOWEST AV Node to give ventricle enough time to fill with blood


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The Cardiac Action Potential

Atrial and VentricularMyocardium, Purkinje Fibers

SA Node, AV Node, His-Purkinje System

specialized for CONTRACTION demonstrate AUTOMATICITY

Phase 0

Upstroke

sudden, fastdepolarization

OPENING of voltage-dependent Na

+channels

inward Na+

current

OPENING of Ca2+

channels inward Ca

2+current

IN > OUT depolarization IN > OUT depolarization

Phase 1

INITIALRepolarization

initial ONLYbec of theplateau phase

CLOSURE of voltage-dependent Na

+channels

NO inward Na+

current OPENING of K

+channels

outward K+

current

ABSENT

IN < OUT repolarization

Phase 2

Plateau

equal inwardand outwardcurrents

OPENING of Ca+

channels inward Ca+ channels

STILL OPEN K+

channels outward K

+current

STILL CLOSED Na+

channels NO inward Na+

current

ABSENT

IN = OUT plateau

Phase 3

Repolarization

repolarizationuntil restingpotential

CLOSURE of Ca+

channels inward Ca+ channels

STILL OPEN K+

channels

outward K+ current STILL CLOSED Na

+

channels NO inward Na+

current

CLOSURE of Ca+

channels

NO inward Ca+ channels OPENING of K+

channels outward K

+current

IN < OUT repolarization IN < OUT repolarization

Phase 4

RestingMembranePotential:~ -90 mV

CLOSED Na+ channels LEAKINGK

+channels

brings membrane potential

close to EEq for K+

LEAKINGNa+

channelsinward Na

+current (If)

slowly depolarizes themembrane towards NaEqfor K

+

IN = OUTSTEADY

membrane potential

IN > OUTSLOW

depolarization

once threshold is reached,new action potential is fired BASIS FOR AUTOMATICITY


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NOTES: SUMMARY OF DIFFERENCES

1. Phase 0:Na+

for conducting cells, Ca2+

for automatic cells2. Phase 4:STEADY for conducting cells, SLOWLY DEPOLARIZING for automatic cells

3. ABSENT Phases 1 and 2 for AUTOMATIC cells Ca

2+for CONTRACTION starts from the inward current DURINGPhase 2 (plateau)

entry of Ca2+

causes more Ca2+

to be released from the SARCOPLASMIC RETICULUM(known as Ca

2+-induced Ca

2+release)

Excitability ability to initiate an action potential in response to depolarization reflects RECOVERY of

Na+

channels

(Recall:Na+ channels are INACTIVATED during depolarization; they RECOVER duringrepolarization/hyperpolarization)

Absolute Refractory Effective Refractory Relative Refractory Supranormal

from start of Phase 0to end of Phase 2

similar to ARP, justslightly longer

from end of Phase 2to start of Phase 4(i.e. from end ofARP to completionof repolarization)

shortly after the endof RelativeRefractory Period

NO action potential can be generated AT ALL

action potential CANbe generated ONLYIF with strongstimulus

action potential CANbe generated EVENWITH weakstimulus

The MyocardiumStructure: SIMILAR to skeletal muscle

SARCOMERE is also the contractile unit of myocardiumSTRIATED appearance also follows the Sliding Filament Model for contraction/shortening actin is pulled towards

the center of the sarcomere

DIFFERENCES WITH SKELETAL MUSCLE1. branching pattern (rather than parallel)2. more mitochondria

3. T-tubules form dyads with SR (rather than triads)4. presence of INTERCALATED DISCS (absent in skeletal muscle) connections between sarcomeres at their ends contain GAP JUNCTIONS provide direct communication between cells for

FASTER spread of action potentials(electrical syncytium)


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Excitation-Contraction Coupling in Myocardium

Myocardium receives actionpotential from:

1. SA Node2. AV Node3. Purkinje fibers4. other myocardial cells

Action potential travels tointerior of cell through T-tubules

t-tubules follow the Z-lines going to the interior of the cell

T-tubules stimulate SR torelease stored Ca

2+

Determinants of amount of Ca2+

release:1. amount of Ca2+ stored in SR SR gets Ca

2+via a Ca

2+/ATPase pump then

sequesters it via Calsequestrin

2. amount of inward Ca2+

current Ca

2+-Induced Ca

2+release Ca

2+derived from inward

current during the Plateau/Phase 2

Ca2+

binds to Troponin C Tropomyosin moves away from actin binding site

Myosin binds to actin bindingsite in the ABSENCE of ATP

if WITH ATP: binding RELEASED can relaxif WITHOUT ATP: binding PRESENT cant relax

in death, muscles become rigid due to the absence ofATP (rigor mortis)

ATP binds to myosin to release

myosin from actin

ATP hydrolyzed to ADP + Pi to

move the myosin head to theplus end of actin

ADP released myosin binds to a NEW binding site in actin

(Recall:myosin is bound to actin if there isNO ATP)

ATP binds to myosin AGAIN torepeat the cycle

the cycle will repeat as long as:1. there is ATP: to cause dissociation and movement2. there is Ca

2+: to move tropomyosin out of the way

Ca2+

taken back by SR RELAXATION occurs when there is no longer any Ca

2+

tropomyosin once again blocks actins binding site


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Contractility (Inotropism) ability of cardiac muscle to develop tension at any given length TENSION DEVELOPED DEPENDS ON THE AMOUNT OF INTRACELLULAR Ca

2+

HR Rate CHRONOtropy from RATE of inward Na

+

currentConduction Velocity DROMOtropy from SIZE of inward Ca2+

currentContractility INOtropy from AMOUNT of intracellular Ca

2+

POSITIVE Inotropy NEGATIVE Inotropy

Definition STRONGER contraction WEAKER contraction

Mechanism GREATER intracellular Ca+

GREATER inward Ca2+

currentLESS intracellular Ca

+

LESS inward Ca2+

current

Factorscausing...

1. HRa. Positive Staircase

(Bowditch Staircase):

HR Ca2+

accumulatewith each heartbeat

b. ExtrasystolicPotentiation: excess Ca

2+

immediately after theextrasystole

2. 1 adrenergic stimulation:a. inward Ca

2+current

during plateaub. Ca

2+sequestration by

SR (phosphorylation ofPhospholamban)

3. Cardiac Glycosides: inhibitNa

+/K

+/ATPase Na

+

Na+/Ca

2+cotransport Ca

2+

accumulates in cell

1. MuscarinicAcetylcholinergic: inwardCa

2+current during plateau


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Length-Tension Relationships (Frank-Starling)

LENGTH-TENSION FORCE-VELOCITY

Kind ofContraction

ISOMETRIC ISOTONIC

Tension varying ConstantLength constant varying (velocity)

GraphX-AxisY-Axis

length: PRELOADtension

tension: AFTERLOADchange in length (velocity)

Relationship PARABOLIC

length tensionUNTIL acertain MAX stretching maximizes the

number of possible cross-links

between actin and myosin

further length tension further stretching brings binding

sites in actin FARTHER frommyosin LESS binding sites

TENSION IS MAX AT AN IDEALPRELOAD

NEGATIVE SLOPE

tension/afterload velocity msc must contract AGAINST a

stronger force

VELOCITY IS MAX IFAFTERLOAD ZERO

NOTES:

PRELOAD length of muscle BEFORE contraction LV end-diastolic volumeAFTERLOAD tension AGAINST WHICH msc contracts aortic/pulm artery pressure


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Ventricular Pressure Volume Loops

startswith...

in between... endswith...

SignificanceVol PressISOVOLUMETRICContraction

closure ofmitral valve

CONSTANT INCopening ofaortic valve

ventricle contracts to

pres but LV pres aortic presblood leaves the ventricleleading to in vol

if aortic pres > LV pres,aortic valve closes nofurther in volume

Volume at END: END-SYSTOLIC VOLUME

ISOVOLUMETRICRelaxation

closure ofaortic valve

CONSTANT DECopening ofmitral valve

ventricle relaxes causing in LV pres butLV pres > LA presmitral valve remainsclosed

VentricularRelaxation

opening ofmitral valve

INCSLOW

INCclosure ofmitral valve

LV pres < LA presMVopens and blood rushesto LV leading to in vol

ventricle contractscausing in pres: onceLV pres > LA pres, mitralvalve closes no further in volume

Volume at END: END-DIASTOLIC VOLUME

NOTES: WIDTH OF LOOP reflects stroke volume

HEIGHT OF LOOP reflects afterload (aortic pres)


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Volume

Pressure

stroke volume

end-diastolicvolume

end-systolicvolume

Effects to Loop

Increasing Preloadincreased end-diastolic volume

Increasing Afterloadincreased aortic pressure

Increasing Contractilitypositive inotropes

increased end-diastolicvolume: loop widenstowards the right

increased contractility(Frank-Starling) strokevolume: left boundary ofloop does NOT change

aortic valve opens at ahigher pressure: loopbecomes taller

stroke volume: loopbecomes narrower

end-systolic volume:left boundary displaced toright

stroke volume: loopwidens

end-systolic volume: leftboundary displaced to left

Volume

Pressure

newloop

Volume

Pressure

newloop

Volume

Pressure

new

loop

OVERALL: loop WIDENS tothe RIGHT

OVERALL: loop NARROWSto the RIGHT, and becomesTALLER

OVERALL: loop WIDENS to theLEFT


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Cardiac Output (Cardiac Function) and Venous Return (Vascular Function) Curve End-Diastolic Volume CO (2o to Frank-Starling Law) Right Atrial Pressure venous return

Mean SYSTEMIC Pressure right atrial pressure at which there is NO flow of blood- ABSENT P between blood pressure and RA nothing drives blood to flow to RA- intersection between venous return curve and the x-axis

RA Pressure orEnd-Diastolic Volume

VenousReturnor

CardiacOutput Cardiac Output

Venous Return

Mean SystemicPressure

Changing the SHAPE of the Graph

Venous ReturnBlood Volume and Venous Capacitance- SAME slope, DIFFERENT Mean Systemic Pressure

BLOOD VOLUME or CAPACITANCE

RA Pressure

VenousReturn

NEWMeanSystemic

Pressure

1. venous return for ALL RA pressure

shift to R2. mean systemic pressureshift to R

BLOOD VOLUME or CAPACITANCE

RA Pressure

VenousReturn

NEW MeanSystemic

Pressure

1. venous return for ALL RA pressure

shift to L2. mean systemic pressureshift to L


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Total Peripheral Resistance- DIFFERENT slope, SAME Mean Systemic Pressure

RESISTANCE

RA Pressure

VenousReturn

venous return for ALL RA pressure butSAME mean systemic pressure slope

RESISTANCE

RA Pressure

VenousReturn

venous return for ALL RA pressure butSAME mean systemic pressure slope

Cardiac Output

Inotropes- SAME x-axis, DIFFERENT slopes

POSITIVE Inotropes

End-Diastolic Volume

CardiacOu

tput

NEWCO

CO for ALL EDV slope

NEGATIVE Inotropes

End-Diastolic Volume

CardiacOu

tput

NEWCO

CO for ALL EDV slopeEQUILIBRIUM or STEADY-STATE POINT: point at which CO and venous return are equal

- can be altered by changing the shape of CO and venous return curves:1. use inotropes2. change total peripheral resistance3. change venous return or venous capacitance


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Stroke Volume Cardiac Output Ejection Fraction

volume ejected by heart perheartbeat (50-80 mL)

volume ejected by heart perminute (~ 5 L)

fraction of end-DIASTOLICvolume ejected per heartbeat(55%)

SV = End-Diastolic VolEnd-Systolic Vol

CO = SV x HREDV

SVEF

Cardiac Output by the FICK PRINCIPLE

)arterypulmonaryO()veinpulmonaryO(

nConsumptioOTOTALCO

22

2

1. determine TOTAL O2 consumption2. O2 Pulmonary Vein = O2 content of PERIPHERAL ARTERY both OXYGENATED

3. O2 Pulmonary Artery = O2 content of MIXED VENOUS BLOOD

both DEOXYGENATED

Stroke Work- work performed by heart per heartbeat

W = Force x Distance = P x VW = (Aortic Pressure) x (Stroke Volume)

- reflect O2 consumption of the heart- Fatty Acids: primary energy source for myocardium

Factors that INCREASE work:1. increased afterload heart must contract AGAINST a load2. increased HR heart does more in a minute3. increased contractility stroke volume increases4. increased size radius = tension


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The Cardiac Cycle: 7 StepsEvent Description ECG Notes

1 Atrial Systole

START:atrial systole

END: mitralvalve closure

atria contracts (atrialkick)

blood ejected toventricle

P wave NOT ESSENTIAL for ventricular filling(30% of ventricular filling only)

Heart Sounds: 4th

sound (due to rushof blood to LV)

LV Pressure: slight LV Volume: at its peak

(due to ending of LV filling) Aortic Pressure: dropping Venous Pulse: a wave (due to atrial

contraction)

2 IsovolumetricVentricularContraction

START:mitral valveclosure

END: aorticvalve opening

ventricle contracts, butwith NO CHANGE involume

mitral valve closes (LV> LA)

aortic valve still closed(LV < aorta)

QRScomplex

Heart Sounds: 1s sound (due tomitral valve closure)

LV Pressure: rapid (due toventricular contraction)

LV Volume: constant (ISOvolumetricsince all valves still closed)

Aortic Pressure: stilldropping

(no flow into aorta yet) Venous Pulse: c wave (due to closure

ofTRICUSPIDvalve)3 Rapid

VentricularEjection

START:aortic valveopening

END: peak ofventricular

pressure

RAPID ejection ofblood into aorta

PEAK ventricularpressure reached

aortic valve opens (LV> aorta) blood flowsout of LV and into theaorta

ONSETof Twave

Heart Sounds: NONE

LV Pressure: continued until MAX(ventricle still contracting)

LV Volume: rapid (blood beingemptied to the aorta)

Aortic Pressure: rapid until MAX(aortic valve opens and blood flows toaorta)

Venous Pulse: c wave (due to closureofTRICUSPIDvalve)


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Event Description ECG Notes

4 ReducedVentricularEjection

START:peak ofventricularpressure

END: aorticvalve closure

SLOWER ejection ofblood into aorta

aortic valve closes (LV< aorta) flow ofblood stops

atria starts to fill

T wave Heart Sounds: 2n

sound (due toaortic valve closure)

LV Pressure: start of LV Volume: continued until MIN

(ventricle already being emptied ofblood)

Aortic Pressure: start of untilincisura (or dicrotic notch)(due to runoff of blood to periphery,while incisura due to closure of aorticvalve)

Venous Pulse: starts to (due toatrial filling)

5 IsovolumetricVentricularRelaxation

START:aortic valveclosure

END: mitralvalve opening

ventricle relaxes, butwith NO CHANGE involume

mitral valve still closed(LV > LA)

aortic valve closes(LV < aorta)

atria continue to fill

END ofT wave

Heart Sounds: NONE

LV Pressure: until MIN(due toventricular relaxation)

LV Volume: constant(ISOvolumetricsince all valves still closed)

Aortic Pressure: initially then (initialdue to closure of aortic valve,while nextdue to runoff of blood)

Venous Pulse: v wave (due to peak ofatrial filling)

6 RapidVentricularFilling

START:mitral valveopening

END: peak ofventricularvolume

PEAK of atrialpressure

mitral valve opens (LV< LA)RAPID flowof blood into LV

BET Tand Pwaves

Heart Sounds: 3r

sound (due to rushof blood to LV)

LV Pressure: still (due tocompliance of ventricle)

LV Volume: rapid (due to rapidentry of blood to LV)

Aortic Pressure: still (due to runoffto periphery, aortic valve still closed)

Venous Pulse:(due to emptying ofaorta)


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Event Description ECG Notes

7 ReducedVentricularFilling

(Diastasis)

START:peak ofventricularvolume

END: atrialsystole

SLOWER flow ofblood to LV

BET Tand Pwaves

LONGEST PART of the cardiac cycle most affected by changes in HR

Heart Sounds: NONE

LV Pressure: still (due tocompliance of ventricle)

LV Volume: slower (due to slowedentry of blood to LV)

Aortic Pressure: still (due to runoffto periphery, aortic valve still closed)

Venous Pulse: starting to (due toreduction in rate of emptying of aorta)

NOTES: HEART SOUNDS

1st

Heart Sound MV/TV closure start of Isovolumetric Ventricular Contraction2

ndHeart Sound AV/PV closure end of Reduced Ventricular Ejection

3rd

Heart Sound rush of bloodt to LV start of Rapid Ventricular Filling4

thHeart Sound atrial kick Atrial Systole

ECG PARTSP Wave Atrial Depolarization Atrial SystoleQRS Complex Ventricular Depolarization Isovolumetric Ventricular Contraction

ONSET of T ONSET of Repolarization start of Reduced Ventricular FillingT Wave Ventricular Repolarization Isovolumetric Ventricular Relaxation

VENOUS PRESSURE WAVESa Wave AtrialSystole Atrial Systolec Wave closure of tricuspid start of Isovolumetric Ventricular Contractionv Wave peak of atrial filling end of Isovolumetric Ventricular Relaxation

VENTRICULAR PRESSURE AND VOLUMEVolume PEAK end of Atrial SystoleVolume MIN end of Reduced Ventricular Ejection

Pressure PEAK end of Rapid Ventricular EjectionPressure MIN end of Isovolumetric Ventricular Relaxation


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Regulation of Blood PressureBaroreceptor Reflex Renin-Angiotensin-Aldosterone

Mode ofAction

NEURAL HORMONAL

Onset andDuration

rapid onsetfast duration (minute-to-minutechanges)

slow onsetlong-term duration

Receptors Baroreceptors (Carotid SINUS)- in wall of bifurcation of common

carotid and in aortic arch

Juxtaglomerular Apparatus- in kidney

StimulusDetected

stretch of wall

carotid sinus: REDUCTION in stretchaortic arch:

Physio Chino

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