University of Zagreb Faculty of Electrical Engineering and Computing

Biomedical Instrumentation Origin of bioelectric potentials

prof.dr.sc. Ratko Magjarevi

Outline
Introduction
Definition of BME Achievements of Biomedical Engineering in 20th Century Challenges of Biomedical Engineering for 21th Century Why to study Biomedical Engineering?

Origin of bioelectric signals

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Human physiology
Science on vital processes and functions in living organisms BME students have special interest in:
Electrophysiology Control mechanisms

A man is a machine, extremely complex, but still a machine (Arthur Vander)

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Electrophysiology
Study of electric properties of biological cells and organs Includs measurement of voltage changes and currents from cell level to organ level In neuroscience, potentials of nerve cells and action potentials are measured

Types of electrophysiological measurements

Electrocardiography (abb. ECG or EKG)- a standard noninvasive procedure for recording electrical potentials of the heart. The record (electrocardiogram), consists of waves that relate to the electrical activity of the heart during each beat. Results - printed on paper or displayed on monitor.

Types of electrophysiological measurements

Electroencephalography (EEG) a standard noninvasive procedure for recording electrical activity of the brain. The record (electroencephalogram), consists of curves that relate to the spontaneous electrical activity of millions of neural cells of the brain. The recording lasts for 20 4 min - 0 and is printed on paper or displayed on monitor.

Types of electrophysiological measurements

Electromyography (EMG) recording the electrical activity produced by skeletal muscles.
Electrooculography (EOG) - measuring the resting potential of the retina. The resulting signal is called the electrooculogram. Other methods: Electroretinography, Audiology, Electrogastrography ...
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Human body structure

Chemical elements Cells Tissue group of similar cells Organ group of similar tissues System functional complex made of different organs Organism functional complex of 11 systems
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Human body composition - the structural level

Chemical level Cellular level Tissue level Organ level System level The level of the organism

Human body chemical composition

Most represented elements (approx. 99,3%):
Hydrogen Oxygen Carbon Nitrogen (H) (O) (C) (N) 63% 26% 9% 1%

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Human body chemical composition

Minerals (approx 0,7%):
Calcium Phosphorus Potassium Sulphur Sodium Chlorine Magnesium (Ca) (P) (K) (S) (Na) (Cl) (Mg)
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Human body chemical composition

Other elements (<0,01%):
Iron (Fe) Iodine (I) Copper (Cu) Zinc (Zn) Manganese (Mn) Cobalt (Co) Chromium (Cr) Selenium (Se) Molybdenum (Mo) Fluorine (F) Tin (Sn) Silicon (Si) Vanadium (V)
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Human organism consists of

Fluids (approx. 2/3 of the weight) + Tissues (groups of similar cells)

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Liquids
Intracellular fluid ( approx. 40%) Extracellular fluid (approx. 20%)
Interstitial fluid (approx. 16%) Plasma (approx. 4%)

The remainder (6-10%) consists of:

Blood Lymphatic fluid Urine Cerebral spinal fluid
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Tissues
NERVOUS (Neural) MUSCLE (Muscular) CONNECTIVE EPITHELIAL

1. NERVOUS (Neural)

1. SKELETAL (Voluntary)

1. FILAMENTARY (Fibrous)

1. VESSELS (Vascular)

2. GLIA CELLS 2. SMOOTH (Cells for excitacion (Involuntary) of brain metabolism) 3. CARDIAC (Involuntary)

2. FAT (Adipose)

2. GLAND (Gladular)

3. CARTILAGINOUS

3. SKIN

4. BONES (Osseous)

4. HAIR (Cilia)
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Cell
Human organism consists of approx. 751018 cells (75.000.000.000.000.000.000) Cell diameter ranges from 0,2 - 120 m Most cells range from 10 - 20 m in diameter Organisms of different sizes (man or elephant) consist of cells similar in dimension, only the number of cells is different

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Cell structure
Subcellular components (1) nucleolus (2) cell nucleus (3) ribosome (4) vesicles (5) rough endoplasmic reticulum (ER) (6) Golgi (7) Cytoskeleton (8) smooth endoplasmic reticulum (9) mitochondria (10) vacuole (11) cytoplasm (12) lizosom (13) centrioles
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Cell membrane
Cell membrane is semipermeable lipid bilayer made of lipids and proteins that separates the intracellular part from the extracellular environment Thickness of 10 nm Semipermeable - the pore width 8 nm Dielectric constant = 5, spec. capacity C = 0.5 to 1 F/cm2 Transit of substances (in and out of cells) is regulated by
Diffusion (from regions of higher concentration to regions of lower concentration) Osmosis (diffusion of water through a semipermeable membrane) Active transmission (from region of lower concentration to regions of higher concentration, requires energy)

State of the membrane is determined by two main factors:

Concentration gradient (diffusion coefficient, D) Electric field (E)

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Concentration in the cell and out of the cell

Phospates Amnino acids Glucose

* mM/l, millimol per liter

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Cell membrane
Intracellular space Extracellular space

a) Cell polarization b) part of the membane c) structure of the membrane

Potassium ions (K+) exit the cell easily, while A- is hard to come out of the cell Na+ is hard to enter, whereas Cl- enters the cell easily Na-K pump ejects Na+ more efficiently than injecting K+ Therefore, outside the cell there is an excess of positive charge and the 20 inside of the cell is negatively charged

Diffusion through semipermeable membrane - the passive process

Ficks law

dmi dcix = S D dt dx

mi = amount of (a particular) substance i [mol] t = time [s] S = membrane surface [m2] D = diffusion coefficient [m2/s] dcix / dx = concentration gradient [mol/m3] of a particular substance i at the possition x

diffusive flux goes from regions of higher concentration to regions of lower concentration, and it is proportional to the concentration gradient (in space).

K+ ions can easily leave the cell, creating an excess positive charge and the potential difference occurs - diffusion takes place until the electric field is established and it stops the process of diffusion

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Sodium - Potassium Pump an active process

Na+ + Y-complex= NaY molecule + Na-pump = Out Na+ + X K+ + X-complex = KX molecule + K-pump = In K+

For each inserted K + ion, 2-5 Na + ions are ejected Na-K pump requires energy:
ATP = ADP + energy ATP - adenosine triphosphate, ADP - adenosine diphosphate
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Resting potential
The resting potential of a cell Nernst equation
u =
u = potential difference [V] R = universal gas constant = 8,314 J/molK T = absolute temperature (0K = -273 C) n = valence of chemical elements whose concentration is considered, potasium inthis case cki , cko = concentration of ions inside and outside the cells F = Faraday constant = 96,5 C/mol E = electric field [V/m]

R T ck 1 ln n F ck 2 cKo [mV] cKi

u = 61.5 log u = 85 mV

T = 37 [C], cKo = 5 [mol/l], cKi = 140[mol/l] Electric field on the membrane kV u 85 [mV] E= = = 85 [ ] d 10 [nm] cm

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Resting potential
Bioelectric potentials are a result of electrochemical activity of excitable cells (in neuros, muscular or glandular system) The resting potential of a cell steady difference in electric potentials between internal and external environment of the cell. Typical values of resting potentials are in range of -50 mV to -100 mV (reference point out of the cell).

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Action potential
Stimuli Depolarization

Stimulus:
Mechanical Chemical Electrical Repolarization threshold

Sudden increases of membrane conductance for Na + ions (1000 times more) - change in polarity of the voltage - depolarization

conductivity

Action potential, showing depolarisation and repolarisation b) Changes in conductivity for 25 sodium and potassium during the action potential

Action potential
S2 30 stimulus S1

threshold -85
Resting potential
a) Action potential b) Two consecutive action potentials, caused by stimuli S1 and S2. Note that the magnitude of S2 is larger than magnitude of S1

After commencement of the action potential , the process can not be stopped by any subsequent stimulus - as long as this state lasts we are talking about the absolute refractory period to When the process starts to calm down and return power to the value at rest, it is possible to re-trigger action potentials using more intense stimulus, even though the voltage has not reached the value at rest - the time when it is possible to re-create the action potentials with a greater intensity of stimulus is called the relative refractory time, tr 26

Action potential
The course:
The stimulus reaches the threshold Increasing membrane permeability for Na + ions After that, permeability for K + increases and Na + ions permeability decrease Reducing permeability for K + ions Active ejection of Na + and injection of K + ions

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Action potential
Excitable cells have the ability to conduct action potentials when adequatly stimulated. An adequate stimulus causes depolarisation of the membrane large enough to reach and exceed the stimulation threshold of the membrane. Adequate excitation causes an action potential, which follows the all ornone rule. The action potential travals along the membrane at constant velocity and without attenuation. At rest, the cell is said to be polarized. After the cell is excited, the potenetial is decreasing depolarisation of the cell membrane. Returning of the cell potential to the resting value is called repolarisation. After repolarisation, for a short period of time, the cell potential is increased which is called hyperpolarisation. During that period, a stimulus has to be of larger magnitude in order to excite a cell.

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Cell membrane model

Hodgkin and Huxley Nobel prize, 1963
Resting potential u Intracellular medium

Extracellular medium (liquid) Diagram of network equivalent circuit of a cell membrane showing voltage sources of main ions Ei, membrane conductances gi and membrane capacitance C.

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Nerve cell
Cell body (soma)

Dendrites Nucleus

Axon Synapses Intercommunicating links between neurons (neuro-neuro junctions) are called synapses.

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Transfer of stimulus - Synapse

Stimulus stimulates neurotransmitter secretion in the synaptic cleft and stimulates (or not) the next nerve cell Neurotransmitters:
Acetylcholine Monoamines Amino acids Peptides
Neurotransmitter release postsynapsis Action potential presynapsis Synaptic gap

Synapses can be:

excitation inhibitory
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Synapse activity

Stimuli

Stimulation threshold depolarisation Excitatory synapsis

Inhibitory synapsis

hyperpolarisation

Changes in resting potential caused by activity at an excitatory and an inhibitory synapse

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Temporal and spatial summation

Stimuli

Stimulation threshold

Temporal sumation

Spacial sumation

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Types of synaptic connections

Neuron neuron junctions Neuromuscular junctions communication links between neurons and muscle fibers. These are small regions of the muscle fiber, called neuromuscular plates.

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Types of nerve fiber

Myelinated fibers
Axon is insulated by a seath of myelin (lipoprotein) Myelin seath interrupted every 1-2 mm nodes of Ranvier Sodium ion chanells distributed unequally, more at nodes of Ranvier Myelization reduces leakage currents and improves transmission properties (cable like behaviour) faster propagation of action potentials

Unmyelinated
Equal distribution of sodium and potassium channels Leackage current sourses more expressed Slower propagation along the axon (cable)
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Potential difference measured along the fibre

Stimulus

Schwan cell

Propagation of stimuli in unmyelined and in myelined nerve fibers

myelin

Node of Ranvier
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Human Sences
Enable tracking of happenings in the outside world Convert external information in forms suitable for processing in the nervous system

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Types od sences according to types of stimulus

Mechanoreceptors
touch, pressure, hearing

Thermoreceptors
hot, cold

Chemoreceptors
smell, taste (salty, sweet, sour and bitter), reaction to O2 and CO2

Photoreceptors
vision

Nocireceptors
pain, damage
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Sences

Sences that react to touch and pressure: The free end - without a myelin sheath Nerve ending in a cocoon - Pacinij corpuscles, Krause end bulb, Markel corpuscle, Meissner corpuscles, Ruffine corpuscle
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Receptor potentials
Sensory cells have a high threshold of excitability Stimulus does not produce an action potential - the potential value changes - receptor or generator potential Change in resting potential due to intensity of the stimulus
linear logarithmic
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Receptor potentials
Stimuli Node of Ranvier

a) b) c)

Tactile receptor excited by the force F Receptor potential Ur and frequency f of action potentials against relative intensity of excitation; I0 thresholf of stimulation Intensity of excitation I, receptor potential Ur and action potential Uak generation - frequency response
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Accommodation, habituation
Receptor potential is reduced when stimulation lasts a longer period of time with the same intensity
most expressed for the sence of touch negligible for the sense of pain

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Voltage - frequency conversion

Voltage frequency conversion occurs at the first node of Ranvier on the axon Pulse frequency is linearly proportional to the receptor potential The relationship between pulse frequency and intensity of stimulation:

f = k (I I 0 )

n <1 - sence compression (eg, logarithmic curve), present in vision and hearing n = 1 - a linear relationship
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Sences with nonlinear (logarithmic) relationship between stimulus intensity and sensory reception
Nonlinear (logarithmic) relationship is necessary whenever there are large differences in the intensity of stimuli E.g., the ratio between whisper sound intensity and sound of a jet airplane, or between moonligth and day sunlight is 1:106 In a logarithmic relations, the frequency of generated action potentials changes in ratio 1:13,8 The highest frequency of action potentials in nerve fibers is corresponding to the reciprocal value of absolute refractory time and is approximately 1000 Hz, Most receptors have highest frequency in order of magnitude of hundred Hertz
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Sences with nonlinear (logarithmic) relationship between sense and stimulus intensity

Sence S is proportional to the relative intensity change I (Weber-Fechner Low):

I dI dS = k S = k I I dI 1 dS = 0 I k 1 ln I S + C = 0, ln I 0 = C za S = 0 k I S = k ln I0

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Sence of hot and cold

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Sence of sight
The sence in which we receive most information from the outside world
cerebral cortex provides the greatest surface area for receiving, processing and synthesis of the image

Sences are located in the eyes (photoreceptors)

sensitive to light intensity (stick cells, 125106) sensitive to color (cone cells, 6106)
Red, green, blue
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Sence of sight

Cross section of the eye and the cross section of retina

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Sence of sight
A sharp image comes on the central part of the retina where there are mostly cones yellow spot (fovea centralis) At the point where ganglion cell axons (up to 106) exit, there are no photoreceptors and the image that comes on that part of the retina is not visible - blind spot

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Cones and sticks arrangement along the retina

Sticks Cones

Blind spot

Fovea

Sticks are deployed across the retina Cones concentration is highest in the 4 area around the Fovea
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Information reduction
Reducing the useless information load of the vision center Reduction is allowed by the horizontal and amacrine cells - predominantly contain inhibitory synapses Enable good observation of the contour (outline) of an object, rather than the contents inside the contour, which often (except data on the color and intensity of light) do not contain other important information
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Literature
A. anti: Biomedicinska elektronika, kolska knjiga, Zagreb; 1995 John G. Webster: Medical Instrumentation Chapter 4, The origin of biopotentials R.S. Kandpur: Biomedical Instrumentation, Chapters 1.1-1.3, 2.1

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