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University of Zagreb Faculty of Electrical Engineering and Computing

Biomedical Instrumentation Origin of bioelectric potentials

prof.dr.sc. Ratko Magjarević

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

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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.

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0 and is 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 . 6 .

The resulting signal is called the electrooculogram.Types of electrophysiological measurements • Electromyography (EMG)• recording the electrical activity produced by skeletal muscles.. • Electrooculography (EOG) . Electrogastrography . 7 . • Other methods: Electroretinography..measuring the resting potential of the retina. Audiology.

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 • • • • • 8 .

Human body composition .the structural level • • • • • • Chemical level Cellular level Tissue level Organ level System level The level of the organism 9 .

3%): – Hydrogen – Oxygen – Carbon – Nitrogen (H) (O) (C) (N) 63% 26% 9% 1% 10 .Human body chemical composition • Most represented elements (approx. 99.

7%): – Calcium – Phosphorus – Potassium – Sulphur – Sodium – Chlorine – Magnesium (Ca) (P) (K) (S) (Na) (Cl) (Mg) 11 .Human body chemical composition • Minerals (approx 0.

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) 12 .

Human organism consists of Fluids (approx. 2/3 of the weight) + Tissues (groups of similar cells) 13 .

20%) – Interstitial fluid (approx.Liquids • Intracellular fluid ( approx. 4%) • The remainder (6-10%) consists of: – – – – Blood Lymphatic fluid Urine Cerebral spinal fluid 14 . 40%) • Extracellular fluid (approx. 16%) – Plasma (approx.

GLIA CELLS 2. SKELETAL (Voluntary) 1. HAIR (Cilia) 15 . FILAMENTARY (Fibrous) 1. SKIN 4. VESSELS (Vascular) 2. CARTILAGINOUS 3. BONES (Osseous) 4. NERVOUS (Neural) 1. SMOOTH (Cells for excitacion (Involuntary) of brain metabolism) 3. FAT (Adipose) 2. CARDIAC (Involuntary) 2.Tissues NERVOUS (Neural) MUSCLE (Muscular) CONNECTIVE EPITHELIAL 1. GLAND (Gladular) 3.

2 .20 µm in diameter • Organisms of different sizes (man or elephant) consist of cells similar in dimension.000.000.000) • Cell diameter ranges from 0. only the number of cells is different 16 .120 µm • Most cells range from 10 .000. 75·1018 cells (75.000.000.Cell • Human organism consists of approx.

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 17 .

5 to 1 μF/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.the pore width 8 nm Dielectric constant ε = 5.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 . spec. capacity C = 0. requires energy) • State of the membrane is determined by two main factors: – Concentration gradient (diffusion coefficient. D) – Electric field (E) 18 .

millimol per liter 19 .Concentration in the cell and out of the cell Phospates Amnino acids Glucose * mM/l.

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

Diffusion through semipermeable membrane . and it is proportional to the concentration gradient (in space). • K+ ions can easily leave the cell.the passive process • Fick’s 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. 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 21 .

adenosine diphosphate 22 . ADP .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.adenosine triphosphate.Sodium . 2-5 Na + ions are ejected Na-K pump requires energy: ATP = ADP + energy ATP .

314 J/molK T = absolute temperature (0K = -273 °C) n = valence of chemical elements whose concentration is considered. cKo = 5 [mol/l]. potasium inthis case cki .5 log ∆u = −85 mV T = 37 [°C]. cKi = 140[mol/l] Electric field on the membrane kV ∆u 85 [mV] E= = = 85 [ ] d 10 [nm] cm 23 .Resting potential The resting potential of a cell Nernst equation ∆u = ∆u = potential difference [V] R = universal gas constant = 8. 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.

muscular or glandular system) The resting potential of a cell – steady difference in electric potentials between internal and external environment of the cell. 24 .Resting potential Bioelectric potentials are a result of electrochemical activity of excitable cells (in neuros. Typical values of resting potentials are in range of -50 mV to -100 mV (reference point out of the cell).

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 .

it is possible to re-trigger action potentials using more intense stimulus. Note that the magnitude of S2 is larger than magnitude of S1 • • After commencement of the action potential .Action potential S2 30 stimulus S1 threshold -85 Resting potential a) Action potential b) Two consecutive action potentials.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.the time when it is possible to re-create the action potentials with a greater intensity of stimulus is called the relative refractory time. caused by stimuli S1 and S2. tr 26 . even though the voltage has not reached the value at rest . the process can not be stopped by any subsequent stimulus .

permeability for K + increases and Na + ions permeability decrease – Reducing permeability for K + ions – Active ejection of Na + and injection of K + ions 27 .Action potential • The course: – The stimulus reaches the threshold – Increasing membrane permeability for Na + ions – After that.

After repolarisation. the potenetial is decreasing – depolarisation of the cell membrane. At rest. the cell potential is increased which is called hyperpolarisation. Adequate excitation causes an action potential. • • • • 28 . Returning of the cell potential to the resting value is called repolarisation. The action potential travals along the membrane at constant velocity and without attenuation. for a short period of time. the cell is said to be polarized. An adequate stimulus causes depolarisation of the membrane large enough to reach and exceed the stimulation threshold of the membrane. After the cell is excited. a stimulus has to be of larger magnitude in order to excite a cell. During that period. which follows the all –ornone rule.Action potential • • • Excitable cells have the ability to conduct action potentials when adequatly stimulated.

Cell membrane model • Hodgkin and Huxley – Nobel prize. membrane conductances gi and membrane capacitance C. 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. 29 .

30 .Nerve cell Cell body (soma) Dendrites Nucleus Axon Synapses Intercommunicating links between neurons (neuro-neuro junctions) are called synapses.

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 31 .Transfer of stimulus .

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 32 .

Temporal and spatial summation Stimuli Stimulation threshold Temporal sumation Spacial sumation 33 .

34 . These are small regions of the muscle fiber. called neuromuscular plates.Types of synaptic connections • Neuron – neuron junctions • Neuromuscular junctions – communication links between neurons and muscle fibers.

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) 35 .

Potential difference measured along the fibre Stimulus Schwan cell Propagation of stimuli in unmyelined and in myelined nerve fibers myelin Node of Ranvier 36 .

Human Sences • Enable tracking of happenings in the outside world • Convert external information in forms suitable for processing in the nervous system 37 .

reaction to O2 and CO2 • Photoreceptors – vision • Nocireceptors – pain. damage 38 . taste (salty. hearing • Thermoreceptors – hot. cold • Chemoreceptors – smell. pressure. sour and bitter). sweet.Types od sences according to types of stimulus • Mechanoreceptors – touch.

Ruffine corpuscle 39 .Sences • Sences that react to touch and pressure: • The free end .without a myelin sheath • Nerve ending in a cocoon . Markel corpuscle.Pacinij corpuscles. Krause end bulb. Meissner corpuscles.

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 40 .

I0 – thresholf of stimulation Intensity of excitation I.frequency response 41 . receptor potential Ur and action potential Uak generation .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.

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 42 .

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 – n <1 .sence compression (eg.a linear relationship 43 . present in vision and hearing – n = 1 . logarithmic curve).

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.g. • Most receptors have highest frequency in order of magnitude of hundred Hertz 44 . the frequency of generated action potentials changes in ratio 1:13. the ratio between whisper sound intensity and sound of a jet airplane.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.. or between moonligth and day sunlight is 1:106 • In a logarithmic relations.

ln I 0 = −C za S = 0 k I S = k ln I0 45 .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.

Sence of hot and cold 46 .

green. processing and synthesis of the image • Sences are located in the eyes (photoreceptors) – sensitive to light intensity (stick cells. blue 47 .Sence of sight • The sence in which we receive most information from the outside world – cerebral cortex provides the greatest surface area for receiving. 6·106) • Red. 125·106) – sensitive to color (cone cells.

Sence of sight Cross section of the eye and the cross section of retina 48 .

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.blind spot 49 . there are no photoreceptors and the image that comes on that part of the retina is not visible .

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 50 .

rather than the contents inside the contour.Information reduction • Reducing the useless information load of the vision center • Reduction is allowed by the horizontal and amacrine cells . which often (except data on the color and intensity of light) do not contain other important information 51 .predominantly contain inhibitory synapses • Enable good observation of the contour (outline) of an object.

Školska knjiga. Kandpur: Biomedical Instrumentation. Chapters 1.1-1.Literature • A.3. 1995 • John G. Webster: Medical Instrumentation Chapter 4. The origin of biopotentials • R. Zagreb.S. Šantić: Biomedicinska elektronika.1 52 . 2.