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Outline
Resting membrane potentials
Action potential
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RMP
Definition
It is a steady state potential which exists acrossthe cell membrane
It is always hyperpolarized
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RMP
SA node -60 mv
Atrium -90mv
Ventricles -90 mv
Skeletal muscles -70mv
Smooth muscle -60mv
Peripheral nerves -70 mv
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RMP
Determinants of RMP?
Electrolyte
Na/K ATPase pump Intracellular protein
Gibbs Domann
Concentration gradient
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RMP
Electrolytes / concentration gradients
ICF ECF
Na 10-20 135-145
K 150 3-5
Cl 10-20 110
100x
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RMP
The membrane is more permeable to Na and K ,so these ions tend to leak across the membranedown according the concentration gradient
The membrane is 100 times more permeable to K So, there is more K is lost from the cell than Na
enters to the cells
Therefore, net result-larger amount of positive
charges has left the cell than entering it.
Thus, that is why cell are semipermeable
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Na/K ATPase pump
It pumps more Na out from the cell than K ispumped in
( 3Na out: 2K in)
It maintains the RMP
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Intracellular protein
There are negatively charged intracellularly
So RMP is negative
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Gibbs- Donnan effect
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The Donnan Effect
Which fluid compartments are high in protein?
intracellular fluid plasma
Which fluid compartment is low in protein? interstitial fluid
Fig. 1-27 Ganong
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The Donnan Effect
Proteins are impermeant polyanions.
Proteins are impermeant to the membrane.
due both to size and charge
Most proteins have a net negative charge.
This negative charge is balanced by cations, typically
monovalent cations. K+for intracellular fluid
Na+for plasma
Fig. 12.11
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The Donnan Effect
When Donnan and Gibbs analyzed the situation
mathematically, they showed that in and outcould not be in electrochemical and osmoticequilibrium at the same time.
(see Ganong)
As a result of the osmotic imbalance, water will
flow into a compartment (cytosol, blood plasma)
that contains more protein. The portion of the osmotic pressure that is due to the
effects of protein is called colloidal osmotic pressure.
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The problem:Because of theDonnan effect, cellswill swell and burst.
The solution:
For animal cells, thesodium pump solves
the problem. Na+pumped out
Cl-follows Na+
H2O follows NaCl
Alberts et al.,Molecular Biology of the Cell
Animal cells must
have sodium pumps.
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Nernst Equation
at equilibriumthese opposing energiesmust be equal
therefore by rearrangement, viz. Calculate one ion
o
im
K
K
zF
RTE
ln
E
K
KK
i
o
615. log
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GOLDMAN CONSTANT-FIELD EQUATION
V = RT In PK+[K+]o + PNa+[Na
+]o + PCl- [Cl-]i
F PK+[K+]i + PNa+[Na
+]i + PCl- [Cl-]o
The magnitude of the membrane potentialat any given timedepends, of course, upon the distribution of Na+, K+ and Cl-and the permeability of the membraneto each of these ions.
It calculate 3 ions
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THE ACTION POTENTIAL
An action potential is the sequence ofchanges in the membrane potential thatoccurs during the transmission of anelectrical signal along the cell membrane,as measured at a specific point on a nerve
or muscle cell membrane.
depolarization
repolarization
~ 1 ms
Fig. 12-13
Fig. 2-6Ganong
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The Action Potential
skeletal muscle fibers
axons of neurons
Fig. 12.13
Fig. 12.12Fig. 11.1
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Phase 1 whn a nerve is stimulated, it initiates
the ligand-gated Na channels, n there will beinflux of Na ions initiating depolarization
Phase 2 whn the depolarization reaches thethreshold potential ard -55mV, it opens up thevoltage gated fast Na channels
Phase 3- massive influx of Na ions
Phase 4 the potential overshoots the
isopotential line to ard + 30mV ( positive spikeAP)
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Phase 5 Na channels closed, K channelsopen , and there will be K efflux
Repolarization
Phase 6 due to continuation of K efflux ,there will be hyperpolarization
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Action Potentials
Characteristics:
1. Stereotypical size and shape2. Propagation to adjacent sites
3. All-or-none response
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Action Potentials:
Characteristics1. Stereotypical size and shape
Each action potential for any cell type looks identical.
It depolarizes to the same potential.
It repolarizes back to the same resting potential.
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-70 mV
0 mV
1.0 2.0
Action Potential
Resting membrane potential
Time (milliseconds)
Voltage
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Action Potentials :
Characteristics2. Propagation to adjacent sites
The action potential moves along the axon in a wave of
changing membrane potential. After an action potential, the membrane is in a
refractory state so the propagation is in one directiononly.
This action potential propagates from one end of thenerve to the other.
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A
B
C
-+
-+
-+
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
Activeregion
Propagation of action potentials(in unmyelinated fibres)
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Myelin sheath
Action potential
Node of Ranvier
-+ -
+ +-
+- +
- -+
Saltatory conduction in myelinated fibres
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2
4
6
8 myelinated
unmyelinated
Effect of myelination on speed of propagation
Fibre diameter (m)
Conductionvelocity(m
/s)
1 2 3 4
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Action Potentials :
Characteristics3. All-or-none response
If an excitable cell is depolarized to threshold in a
normalmanner, then the occurrence of an actionpotential is inevitable.
On the other hand, if the membrane is not depolarizedto threshold, no action potential can occur.
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-100
-50
0
+50
Threshold potential
Resting membrane potential
Increasing subthreshlod stimuli
Membranepotential(mV)
Time|----------------|
1 ms
All-or-none action potential
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Compound action potentials
Peripheral nerves contain a mixture of fibres
Classified according to
Function
Diameter
Conduction velocity
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Table of compound action potential
Fibre Function Diameter
(m)
Conduction
velocity
(m/s)
A
Skeletal motor, joint position
Touch, pressure
Muscle spindle motor
Pain, temperature touch
10-20
5-10
3-6
2-5
60-120
40-7-
15-30
10-30
B Preganglionic autonomic 1-3 3-15
C Pain 0.5-1 0.5-2
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Voltage
(V)
Time (ms)
Compound action potential
A
B
C
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The electrical signals generated by the action
potentials can be sensed using skin or needleelectrodes placed near the muscle. This is thebasis of electromyography.
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Electroencephalography
Is recording of spontaneous activity of thebrain
Generated by pyramidal cells in cortical layers1, 2 and 5
Its a summation of excitatory and inhibitory
postsynapticpotentials in pathways running
from thalamic nuclei to cortex.
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Eeg
4 types of waveform :
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Occurs Hz Voltage(microv)
beta Fully awakeMaybe also produced by volatile
and IV anaesPrecentral cortex
15-25 20
alpha TransitionalAwake,relaxed with eyes closedOccipital cortex
10-15 20-50
theta SleepOccurs in children, elderlyMay indicates dysfx of drugs
1-5 20-50
delta Occurs during sleep during stage3 and 4 of NREM
0.5 1 >50
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Application of EEG
In tumor and epilepsy shows high voltagespike waves
Cerebral infarcation low volatge and low
frequency Thiopentone, propofol, etomidate, and
volatile agents produce initial fast frontalbeta, then frontal alpha spikes with highampitude , then 1-3 HZ delta burstsuppression with high amplitude , then noisoelectric EEG
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Application of EEG
Ketamine frontal rhythmic delta with highamplitude, then intermittent, polymorphicdelta with large amplitude interspersed withlow amplitude beta. NO EEG silence
BZD- no burst suppression and no isoelectricEEG
Opiods dose related low frequency andhigh amplitude, no isoelectric EEG
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Sleep
Is a state of unconsiousness from which aperson can be aroused by a sensorystimulation
Involves decrease activity of RAS(reticularactivation system)
2 stages :
NREM or slow-wave sleep(4 stages)
REM( tonic and phasic)
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Stages of sleep
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Influence of anaesthesia and
surgery during sleep NREM anaesthetic stages REM- post op complication
Why???? In NREM, mainly is by parasympathetic In REM, esp during the phasic phase is mainly by
sympathetic and is predominant during post op Day1
In REM, thr wil be impaired resp fx
Maldistribution of ventilation , impaired V/Q matchingwhich lead to arterial hypoxemia
Thus, MI, cerebral impairment and hypoxemia iscommon post op Day 1
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Depth of anaesthesia for
awareness Awareness Inadvertent return to conciousness during a supposed
GA with or without recall
Techniques that monitored depth ofanaesthesia: MAC
BIS(bispectral index)
Vital sign Entropy
TCI/TIVA ( plasma concentration drug)
IFT(isolated forearm tech)
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BIS
It monitors record raw EEG which altersanaesthesia and after processing produces adimensionless number from 0 -100 which is
an index of probability that the pt is aware
Put at the frontal lobe
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Limitation of BIS
Site of operation
Cant do in children
Organic brain lesion
Psy problem
Drugs like etomidate and ketamine
Costly Artifacts by surgery
diathermy/cauterization/vibration
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