Medical

physics 2.

Bio-
electricity -
1.

Szeged, February 17, 2022.

What you will be in focus on the next two lectures?

1. What kind of electrical signals does an MD measure today?

(ECG, EEG, EP [cortical evoked potential], EMG, ECoG electro-corticogram [
invasive], ERG electro-retionogram,)

2. What signals does the researcher measure (extra- and intracellular, transepithelial
potential, field potential, etc.) and why?

3. Bioelectricity as an integral feature of living organisms

4. Electrical characteristics of cells and tissues (voltages, currents, how and how to
measure them)

5. Physical (mathematical) modeling of cellular and tissue-level electricity: the Nernst

equation, the Goldman equation, linear cable theory, and the Hodgkin-Huxley model of
action potential generation and propagation

6. Fundamentals of measuring and processing electrical signals that can be derived

from the body surface
The living organs/organisms exhibit electric properties

Clinical electrophysiology is the study of how electrophysiological principles and technologies can
be applied to human health.
For example, clinical cardiac electrophysiology is the study of the electrical properties which
govern heart rhythm and activity.

Electrocardiography is the process of producing in electrocardiogram (ECG or EKG), a recording – a graph

of voltage versus time – of the electrical activity of the heart using electrode placed on the skin.

Electroencephalography (EEG) is an electrophysiological monitoring method to record electrical activity

of the brain. It is typically noninvasive, with the electrodes placed along the scalp. Event-related
potentials (ERPs) are very small voltages generated in the brain structures in response to specific events
or stimuli. They are EEG changes that are time locked to sensory, motor or cognitive events that provide
safe and noninvasive approach to study psychophysiological correlates of mental processes. Event-
related potentials can be elicited by a wide variety of sensory, cognitive or motor events.

Electromyography (EMG) is an electrodiagnostic medicine technique for evaluating and recording the
electrical activity produced by skeletal muscles.

Common features:
• Low voltage (amplification required)
• Bad signal/noise relationship (it requires filtering)
• Continuous signals (sampling, storage)
• Data reduction (finding characteristic parameters, shape, frequency analysis, etc.)
 Electrocardiography- electrocardiogram

Discovery of EKG (EKG)

Willem Einthoven (1860-1927) Dutch physiologist
Signal is in the range of several ~mV
The Nobel Prize in Physiology or Medicine 1924 was
awarded to Willem Einthoven "for his discovery of the
mechanism of the electrocardiogram."

Contemporary and
present ECG record
(standard layout
paper)
constant speed helps
timing
When and for what purpose are ECGs performed - and how?

The purpose of ECG measurement is to examine the

propagation of electrical stimuli in the heart.
It allows you to analyze the following:
1. heart rate (arrhythmia!)
2. origin of stimulus and conduction velocity
3. myocardial wall-thickness
4. possible blood supply disorders of the heart muscle
(infarction or functional damages coronal blood
vessels)
(Today additional diagnostic means: ultrasound [+
Doppler UH], catheter, CT and isotope examination – and
imaging)
Who needs it ?
1. diagnostic purpose - circulatory disorder
2. expected cardiovascular risk (surgery, anesthesia)
3. Intensive care (continuous monitoring)
4. Routine screening (sport, age, other risk groups, etc.)
There are various, standardized electrode positions (configurations)

„classical” limb leads (Einthoven)

Chest leads (Wilson)

Highly conductive electrodes (large

surface area, sweat is an electrolyte !
- small half-cell potential [see
chemistry !!] - electrode material
means - galvanic coupling - electrode
Intracardial ECG paste - motion artifacts [electrical] -
(cardiac surgery, catherization, abblation ) anatomy (fat, skin, etc.)
The origin of ECG signals - mainly the electrical activity of the cardiac muscle
The origin of the electrical signals conducted from the body surface
(or from close to the heart or inside the heart) is the rhythmic
depolarization and repolarization of individual but also electrically
connected cells (mainly myocardial cells).

In physiological case, an electrical signal originating from the sinus

node propagates throughout the conducting system and initiates
depolarization of the myocardium, which is synchronized through
electrical synapses. However, there are many groups of pacemaker
cells with various rhythms, so rhythm generation may develop
elsewhere.

All myocardial cells can be stimulated and depolarized - the

transmembrane potential is changing – it elicits periodic ion
movement – it is periodic [ alternating] currents - periodically
changing electric and magnetic fields - their magnitude and change
in time can be detected and measured !
G

G
The transmembrane conductivity is not uniform (G=1/R)-
In cell-cell relationship- gap junctions- easier ion movement- less
resistance
The electric field of the cells (transmembrane field varies in time - direction and
magnitude) is a vector - many of them have a resultant vector

Vectror cardiogram and manifestation

(0 vector is a horizontal line)

t
What is a bioamplifier and why is bio amplifier required?
Generally, biological/bioelectric signals have low amplitude and low frequency. Therefore, to increase the
amplitude level of biosignals amplifiers are designed. The outputs from these amplifiers are used for further
analysis and they appear as ECG, EMG, or any bioelectric waveforms. Such amplifiers are defined as Bio
Amplifiers or Biomedical Amplifiers.
Basic Requirements for Biological Amplifiers
1.The biological amplifier should have a high input impedance value. The range of value lies between 2 MΩ
and 10 MΩ depending on the applications. Higher impedance value reduces distortion of the signal.
2.When electrodes pick up biopotentials from the human body, the input circuit should be protected. Every
bio-amplifier should consist of isolation and protection circuits, to prevent the patients from electrical
shocks.
3.Since the output of a bioelectric signal is in millivolts or microvolt range, the voltage gain value of the
amplifier should be higher than 100dB.
4.Throughout the entire bandwidth range, a constant gain should be maintained.
5.A bio-amplifier should have a small output impedance.
6.A good bio-amplifier should be free from drift and noise.
7.Common Mode Rejection Ratio (CMRR) value of amplifier should be greater than 80dB to reduce the
interference from common mode signal.
8.The gain of the bio-amplifier should be calibrated for each measurement.
 Electroencephalography (EEG) is an electrophysiological monitoring
method to record electrical activity of the brain. It is typically
noninvasive, with the electrodes placed along the scalp, although
invasive electrodes are sometimes used, as in electrocorticography,
sometimes called intracranial EEG or electrocorticogram (ECoG)

EEG waves are named based on their frequency range using Greek
numerals. The most commonly studied waveforms include delta (0.5
to 4Hz); theta (4 to 7Hz); alpha (8 to 12Hz); sigma (12 to 16Hz) and
beta (13 to 30Hz).

German physiologist and psychiatrist Hans

Berger (1873–1941) recorded the first human
EEG in 1924.Expanding on work previously
conducted on animals by Richard Caton and
others, Berger also invented the
electroencephalogram (giving the device its
name), an invention described "as one of the
most surprising, remarkable, and momentous
developments in the history of clinical
neurology".

Korabeli EEG regisztrátum (alul időskála)

 EEG is most often used to diagnose

• epilepsy,
• sleep disorders,
• depth of anesthesia,
• coma, encephalopathies,
• and brain death.

There are active electrodes and reference

(ground stabile 0 V)
Unipolar and bipolar leads

EEG used to be a first-line method of diagnosis for tumors, stroke and

other focal brain disorders,[but this use has decreased with the advent of
high-resolution anatomical imaging techniques such as magnetic
resonance imaging (MRI) and computed tomography (CT).
 Monopolar lead (in general and specific for EEG)
In monopolar/unipolar configuration the lead is placed on the body surface
(chest,scalp,skin), while the other is placed at an area of zero potential.
In conventional scalp EEG, the recording is obtained by placing electrodes on the scalp with a
conductive gel or paste. In most clinical applications, 19 recording electrodes (plus ground
and system reference) are used. Each channel represents the difference between a certain
electrode and a designated reference electrode. Common ground points in EEG
recording: nose, ears, mastoids, forehead. The purpose of grounding is to reduce
noise .
Bipolar lead
a record obtained with two electrodes placed on different regions of the body, each electrode
contributing significantly to the record; for example, a standard limb lead (in ECG), but it is used
in EEG. To record bipolar EEG, you will need an EEG amplifier for each pair of electrodes that
you want to calculate the potential difference between.

Visual vs. computerized frequency analysis (Fourier

analysis, see: first semester- signal analysis)
Origin of EEG waves
Basis: excitable cells- action potentials and repolarizations –huge amount to summarize in space and time)
The EEG consists of the summed electrical activities of populations of neurons, with a modest contribution
from glial cells. The neurons are excitable cells with characteristic intrinsic electrical properties, and their
activity produces electrical and magnetic fields. These fields may be recorded by means of electrodes at a
short distance from the sources (the local EEG or local field potentials, LFPs), or from the cortical surface
(the electrocorticogram or ECoG)
Due to their unique orientation with their long apical dendrites perpendicular to the cortical surface, large
cortical pyramidal neurons in deep cortical layers play a major role in the generation of the EEG. Specific
and non-specific thalamic nuclei, as well as distant cortical areas, terminate on these apical dendrites and
form myriads of excitatory and inhibitory afferents.
An event-related potential (ERP or evoked potential [EP]) is the measured brain response that is the direct result of a
specific sensory, cognitive, or motor event. More formally, it is any stereotyped electrophysiological response to a stimulus.
The study of the brain in this way provides a noninvasive means of evaluating brain functioning.
ERPs are measured by means of electroencephalography (EEG). The magnetoencephalography (MEG) equivalent of ERP is
the ERF, or event-related field.
Here we present visually evoked potentials (VEP) and auditory EPs. The ultimate goal is to
study the electrical properties of the signal conducting system within the CNS. The onset,
the shape and the timing of the filtered responses are analyzed

These methods are for first diagnosis and show directions for
suspected diseases. Additional imaging procedures (CT, MRI ,
PET etc.)
 Electroretinography - electroretinogram (ERG)
Electroretinography measures the electrical responses of various cell types in the retina, including the photoreceptors
(rods and cones), inner retinal cells (bipolar and amacrine cells), and the ganglion cells. Electrodes are placed on the
surface of the cornea or on the skin beneath the eye to measure retinal responses.

Direction of light

During a recording, the patient's eyes are exposed to

standardized stimuli and the resulting signal is displayed showing the
time course of the signal's amplitude (voltage). Signals are very small,
and typically are measured in microvolts or nanovolts. The ERG is
composed of electrical potentials contributed by different cell types
within the retina, and the stimulus conditions (flash or pattern stimulus,
whether a background light is present, and the colors of the stimulus and
background) can elicit stronger response from certain components.
 Electromyography
Electromyography (EMG) is a diagnostic procedure to assess the health of muscles and the nerve cells that
control them (motor neurons). EMG results can reveal nerve dysfunction, muscle dysfunction or problems
with nerve-to-muscle signal transmission. EMG measures the electrical activity of muscle during rest, slight
contraction and forceful contraction. Muscle tissue does not normally produce electrical signals during rest.
Why to perform an EMG test?
tingling
numbness
muscle weakness
muscle pain or cramping
paralysis
involuntary muscle twitching (or tics)
muscle disorders,
disorders that affect the ability of the motor neuron to send electrical signals to the muscle, peripheral nerve
disorders that affect the nerves outside the spinal cord,
nerve disorders,

There are two main types of

EMG electrodes: surface (or
skin electrodes) and inserted
electrodes. Inserted
electrodes have further two
types: needle and fine wire
electrodes.
How to measure and evaluate EMG signals?

Measured EMG potentials range between less than

50 μV and up to 30 mV, depending on the muscle
under observation. Typical repetition rate of muscle
motor unit firing is about 7–20 Hz, depending on
the size of the muscle
Where is bioelectricity coming from and where to go?
Bioelectricity, electric potentials and currents produced by or
occurring within living organisms. Bioelectric potentials are
generated by a variety of biological processes and generally
range in strength from one to a few hundred millivolts. In the
electric eel, however, currents of one ampere at 600 to 1,000
volts are generated. Bioelectric effects were known in ancient
times from the activity of such electric fishes as the Nile
catfish and the electric eel. The experiments of Luigi
Galvani and Alessandro Volta in the 18th century on the
connection between electricity and muscle contraction in
frogs and other animals were of importance in
the development of the sciences of physics and physiology.

All living cells exhibit electric properties

 Electrophysiology is one of the bases when studying cell
biology
• Resting potential and it’s • The theory behind voltage clamp
measurement technique – the importance of such
• Role of the determinant ions experiments
• Discovery and operation of various • patch clamp technique- challenges
types of ion channels and results
• Dynamic vs. static measurements • The living cell as electric entity
• Resting and evoked potentials
bioelectricity may be fundamental to understanding various cellular
behaviours therefore models are used to explore various electrical features
(transmebrane potential, conductivity etc.
The bioelectric potential across a cell membrane is typically about 50 millivolts; this
potential is known as the resting potential. All cells use their bioelectric potentials to
assist or control metabolic processes, but some cells make specialized use of bioelectric
potentials and currents for distinctive physiological functions.

Bioelectrical understanding and engineering of cell biology, Volume: 17, Issue: 166, DOI: (10.1098/rsif.2020.0013)
Composition of cell membrane- functional approach

The cell membrane consists of a lipid bilayer including cholesterols (a lipid component) that sit
between phospholipids to maintain their fluidity at various temperatures. The membrane also
contains membrane proteins, including integral proteins that go across the membrane serving
as membrane transporters, and peripheral proteins that loosely attach to the outer (peripheral) side of the
cell membrane, acting as enzymes shaping the cell.
Function of cell membrane
Separates cells from the envinroment
• Allows cellular specialization
• Membranes within cells: separation and specialization of cellular
organelles
• Signalling
• Transport
 Membrane physics is still a hot topic in reseach – eg. nanomedicine

There are various kinds of membranes- with very complex functions

It is important to see the dimensions
The Lipid Bilayer is a Selective Barrier

inside outside

hydrophobic molecules (anesthetics)

gases (O2, CO2)

small uncharged polar molecules

large uncharged polar molecules

Ions

charged polar molecules (amino acids)

water
25
 Diffusion across cell membrane
• Cell membrane is the boundary between inside & outside…
• separates cell from its environment

Can it be an impenetrable boundary? NO!

IN OUT
food waste
carbohydrates OUT ammonia
sugars, proteins salts
amino acids CO2
lipids IN H2O
salts, O2, H2O products

cell needs materials in & products or waste out

 Membrane potential is a characteristic feature of the living cell

Control of cell state by transmembrane

potential. A sample of physiological
measurements of various cell types
(modified from 108) reveals that
quiescent, terminally differentiated
cells tend to be strongly polarized,
while more plastic cell types (stem
cells, embryonic cells, and cancer cells)
tend to be relatively depolarized.
Interestingly, the liver's Vmem
(abnormally low for an adult
differentiated tissue) groups it with the
morphogenetically labile cells,
consistent with its remarkable
regenerative potential. The relationship
between Vmem and plasticity is a
functional one; for example mature
neurons can be induced to re‐enter the
cell cycle by forced depolarization
BioEssays, Volume: 34, Issue: 3, Pages: 205-217, First published: 11 January 2012, DOI: (10.1002/bies.201100136)
 Equilibrium
1. The process of ions diffusing and changing the membrane voltage
will continue until the membrane potential attains a value
sufficient to balance the ion concentration gradient.
2. At this point the ion will be “in equilibrium”.
3. What is this potential?
 The Nernst Equation

Calculates the membrane potential at which an ion will be in electrochemical

equilibrium.
At this potential: total energy inside = total energy outside

Electrical Energy Term: zFV

Chemical Energy Term: RT.ln[Ion]

Z is the charge, 1 for Na+ and K+, 2 for Ca2+ and Mg2+, -1 for Cl-
F is Faraday’s Constant = 9.648 x 104 Coulombs / mole
R is the gas constant = 8.315 Joules / °Kelvin * mole
T is the temperature in °Kelvin
 The Nernst equation describes the diffusion potential at
equilibrium

RT Cout
E =  ln
zF Cin

E: The equilibrium diffusion potential

R: Gas constant (8.31 J  K-1mol-1)
T: Absolute temperature (K)
F: Faraday constant (96500 Coulomb/mole)
z: Number of charges of single ion (1 with K+ and Na+, 2 with Ca++, -1 with Cl-
)
ln: Natural logarithm (base: e = 2.71828)
Cin, Cout Inside and outside concentrations of the diffusible ion species