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PROF. DR. JOYANTA KUMAR ROY DEPARTMENT OF APPLIED ELECTRONICS & INSTRUMENTATION ENGINEERING NARULA INSTITUTE OF TECHNOLOGY WWW.dr-joyanta-kumar–roy.com SUBJECTS OF DISCUSSION • Introduction to Biomedical Instrumentation • Human Body • Physiology of Heart and Circulatory system • Physiology of Respiratory system • Physiology of Brain and Nervous system • Neurons and Bio-signals The Module -1 course duration : 3 lectures The lecture content will be available at http//www.dr-joyanta-kumar-roy.com DR. J. K. ROY 2 BOOKS AND REFERENCES FOR STUDY 1. Hand Book of Biomedical Instrumentation, R S Khandpur, McGraw Hill 2.BioInstrumentation, John G. Webster, Wiley India 3.Biomedical Instrumentation & Measurement, Cronwell L, Pearson 4.Medical Instrumentation, Application and Design, Webster JS 5. Introduction to Biomedical Instrumentation and measurement, Astor B R, McMillan 6. Introduction to Biomedical Equipment Technology, Carr, Pearson 7. Biomedical Instrumentation, Chatterjee & Millar, Cengage Learning 8. Internet search engines like : Google, Bing etc. DR. J. K. ROY 3 Human Machine Finest Technology Of the world Greatest creation of God Best creature of the Planet DR. J. K. ROY 4 HUMAN BODY The human body is the entire structure of a human organism, and consists of a head, neck, torso, two arms and two legs. By the time the human reaches adulthood, the body consists of close to 100 trillion cells, the basic unit of life. These cells are organized biologically to eventually form the whole body. Organ System: The organ systems of the body include the musculoskeletal system, cardiovascular system, digestive system, endocrine system, integumentary system, urinary system, lymphatic system, immune system, respiratory system, nervous system and reproductive system. Constituents of the human body In a normal man weighing 60 kg Constituent Weight [2] Percent of atoms[2] Oxygen 38.8 kg 25.5% Carbon 10.9 kg 9.5% Hydrogen 6.0 kg 6.3% Nitrogen 1.9 kg 1.4% Calcium 1.2 kg 0.2% Phosphorus 0.6 kg 0.2% Potassium 0.2 kg 0.07% DR. J. K. ROY 5 CARDIOVASCULAR SYSTEM The cardiovascular system comprises the heart, veins, arteries and capillaries. The primary function of the heart is to circulate the blood, and through the blood, oxygen and vital minerals are transferred to the tissues and organs that comprise the body. The left side of the main organ (left ventricle and left atrium) is responsible for pumping blood to all parts of the body, while the right side (right ventricle and right atrium) pumps only to the lungs for re-oxygenation of the blood. The heart itself is divided into three layers called the endocardium, myocardium and epicardium,(liquidation) which vary in thickness and function. Anterior (frontal) view of the opened heart. White arrows indicate normal DR. J. K. ROY blood flow. 6 The cardiovascular system is a complex hydraulic system, which performs the essential service of transportation of oxygen, carbon-di-oxide, numerous chemical compounds and blood cells. Structurally, the Heart is divided into right and left parts. Each parts has two chambers called atrium and ventricle. The 1. 2. 3. 4. Heart has four valves: The Tricuspid valve or Right atria-ventricular valve Bicuspid mitral valve or Left atria-ventricular valve Pulmonary valve Aortic Valve DR. J. K. ROY 7 Heart valve location Function The Tricuspid valve Between right atrium & ventricle Prevent backward flow of blood from right ventricle to right atrium Bicuspid mitral valve Between left atrium & left ventricle Prevents backward flow of blood from left ventricle to left atrium Pulmonary valve At the right ventricle Does not allow blood to come back at right ventricle Aortic Valve Between left ventricle and aorta Prevents the return of blood to the left ventricle from Aorta DR. J. K. ROY 8 THE HEART WALL The pericardium: Outer layer of Heart. It keeps the outer surface moist and prevent friction due to Heart beats The myocardium: Middle layer of the Heart, which made of short cylindrical muscle fibers. The muscle is automatic in action, contracting & relaxing rhythmically through out the life. The endocardium: The inner layer of the Heart provides smooth lining for blood flow Consist of 3 layers DR. J. K. ROY 9 ENGINEERING POINT OF VIEW Fig: Circulatory system DR. J. K. ROY 10 Blood transport mechanism The blood is carried to the various parts of the body(organs) through Blood vessels. The blood vessels are classified into: 1. 2. 3. Arteries : The arteries are thick walled and they carry the oxygenated blood away from the Heart Veins: They are thin walled and they carry deoxygenated blood with carbon di oxide towards heart Capillaries :Smallest and the last level of blood vessels which supply food and oxygen to the organs. From the engineering point of view Heart act as pump and drives blood through blood vessels of the circulatory system consist of four chamber muscular pump that beats 72 per minutes on an average for normal adult, sending blood to every part of the body. The pump act as two synchronized but functionally isolated two stage pump. The first stage of each pump (Atrium) collects blood from hydraulic system and pumps to the second stage (the ventricle). In this process the heart pumps the blood through pulmonary circulation to the lungs and through the systematic circulation to the other parts of the body. Pulmonary circulation: The venous deoxygenated blood flows from right ventricle to the pulmonary artery to the lungs, where it is oxygenated and gives of carbon di oxide. The oxygenated blood then flows through pulmonary veins to the left atrium. Systematic Circulation: The blood is forced through blood vessels which are elastic. The blood flows through left atrium to left ventricle and is pumped through aorta and its branches the arteries to the out of the bodies. Through arterioles (Small and fine arteries) the blood is distributed through capillaries to the human body organs. Where it gives up oxygen and other relevant chemical compounds and taken up carbon di oxide and product of combustion. DR. J. K. ROY 11 The blood returns to the heart from different routes. It usually passes from the Venus side of the capillaries. The heart itself is supplied by two small but highly important arteries, called Coronary arteries. If they blocked by Coronary Thrombosis, Myocardial infraction follows, often leading to fatal situation. The Heart rate is partially controlled by autonomic nervous system and partially by Hormone action. These control the heart pump’s speed, efficiency and blood flow pattern through the system. The circulatory system is the Transport mechanism by which body takes food, oxygen, water and other essentials are transported to the tissue cells and their waste product are transported away. This happens through the diffusion process, in which nourishment from blood cells diffuses through capillary wall into the interstitial fluid. Similarly carbon di oxide and waste product from interstitial fluid diffuses through wall to the blood cell. The condition of the Cardio vascular system is examined by the hemodynamic measurement and recording the electrical activity of Heart muscles (Electro cardiography) For assessing the performance of Heart as a pump, the measurement of cardiac output (amount of blood flow per unit time)i.e by measuring blood pressure and flow at various location of the Circulatory system DR. J. K. ROY 12 THE END OF INTRODUCTION TO THE CARDIOVASCULAR SYSTEM DR. J. K. ROY 13 THE PHYSIOLOGY OF RESPIRATION This presentation takes you through the basic anatomy and physiology of the respiratory system You can complete the questions in your GM402M workbook as you work through this presentation Keep clicking your mouse to take you through the presentation DR. J. K. ROY 14 WHY DO WE NEED TO BREATHE? Breathing gets oxygen into the body so that cells can make energy Cells use this energy to contract muscles and power the thousands of biochemical reactions that take place in the cell every second Without oxygen, cells can’t make energy and without energy, cells would die DR. J. K. ROY 15 IMPORTANT CONCEPT The supply of blood and oxygen to cells and tissues is called PERFUSION If perfusion stops then cells die DR. J. K. ROY 16 ENERGY PRODUCTION Inside the cells most energy is made by the mitochondria. This energy is in the form of ATP* In the process of energy production……… Oxygen is consumed by the cells Carbon dioxide is produced as a waste gas Glucose fuels the process *adenosine triphosphate – a small packet of energy DR. J. K. ROY 17 DR. J. K. ROY 18 HOW DO CELLS GET THEIR OXYGEN? Oxygen (O2) from the air in the lungs diffuses into the blood It is transported in the blood to the cells Oxygen diffuses from the blood into the cells DR. J. K. ROY 19 HOW DO CELLS DISPOSE OF THEIR CARBON DIOXIDE? Carbon dioxide (CO2) from the cells diffuses into the blood It is transported in the blood to the lungs In the lungs carbon dioxide diffuses into the air and is breathed out DR. J. K. ROY 20 MOVEMENT OF O2 AND CO2 BETWEEN LUNGS AND CELLS DR. J. K. ROY 21 THE ANATOMY OF THE RESPIRATORY SYSTEM The respiratory system consists of a series of tubes that transfer air from outside the body to the small air sacs in the lungs where gas exchange take place – the alveoli The diagram on the next page shows the basic layout of the system – label the diagram in your workbook DR. J. K. ROY 22 Look at the structure of the respiratory system and label the diagram in your workbook DR. J. K. ROY 23 ALVEOLI At the end of the smallest bronchioles are the alveoli There are millions of alveoli in each lung Alveoli are surrounded by a network of small blood vessels called capillaries DR. J. K. ROY 24 ALVEOLI AND ADJACENT CAPILLARIES alveoli terminal bronchiole capillaries DR. J. K. ROY 25 GAS EXCHANGE IN THE ALVEOLI Oxygen diffuses from the alveoli to the blood in the capillaries Carbon dioxide diffuses from the blood in the capillaries to the alveoli DR. J. K. ROY 26 DR. J. K. ROY 27 WHAT IS DIFFUSION? Diffusion is a process that occurs when there is a difference in the concentration of a substance between two areas The substance, for example oxygen, will diffuse from an area of high concentration to an area of low concentration No energy is required from the body for this process DR. J. K. ROY 28 DR. J. K. ROY 29 VENTILATION (BREATHING) Breathing air in and out of the lungs – As the ribs rise and fall and the diaphragm domes and flattens, the volume and pressure in the lungs changes It is the changes in pressure that cause air to enter and leave the lungs DR. J. K. ROY 30 VENTILATION (BREATHING) DR. J. K. ROY 31 VENTILATION (BREATHING) Inspiration (breathing in) •Ribs rise and diaphragm flattens •Volume increases and pressure decreases •Air enters the lungs Expiration (breathing out) •Ribs fall and diaphragm domes •Volume decreases and pressure increases •Air leaves the lungs DR. J. K. ROY 32 CONTROL OF VENTILATION As we exercise, the body needs to obtain more oxygen and remove more carbon dioxide (CO2) This is done by increasing the rate and depth of breathing An increase in carbon dioxide in the blood is the main trigger that increases the rate and depth of breathing DR. J. K. ROY 33 CONTROL OF VENTILATION Chemoreceptors in the respiratory centre in the brain stem’s medulla detect an increase in blood CO2 levels The intercostal and phrenic nerves increase the rate and depth of breathing Additional chemoreceptors on arteries near the heart monitor oxygen and blood acidity DR. J. K. ROY 34 Control of Respiration chemoreceptors on aorta and carotid artery brain respiratory centres in medulla heart intercostal nerve to external intercostal muscles phrenic nerve to diaphragm ribs diaphragm DR. J. K. ROY 35 RESPONSE TO HYPERCAPNIA Diseases such as emphysema, bronchitis and asthma can impede the movement of gas between the alveoli and the blood CO2 levels can build up in the blood – known as hypercapnia This stimulates the chemoreceptors in the respiratory centre of the brain The rate and depth of breathing increases to expire more CO2 and reduce levels in the blood DR. J. K. ROY 36 The Physiology of NERVOUS SYSTEM DR. J. K. ROY 37 Central Nervous System: “CNS” Spinal Cord Brain THE SPINAL CORD Foramen magnum to L1 or L2 Runs through the vertebral canal of the vertebral column Functions 1. 2. 3. Sensory and motor innervation of entire body inferior to the head through the spinal nerves Two-way conduction pathway between the body and the brain Major center for reflexes DR. J. K. ROY 39 Spinal cord http://www.apparelyzed.com/spinalcord.html DR. J. K. ROY 40 PROTECTION: DR. J. K. ROY 41 ANATOMICAL CLASSIFICATION Cerebral hemispheres Diencephalon Thalamus Hypothalamus Brain stem Midbrain Pons Medulla Cerebellum Spinal cord DR. J. K. ROY 42 PARTS OF BRAIN Cerebrum Diencephalon Brainstem Cerebellum DR. J. K. ROY 43 SIMPLIFIED… Back of brain: perception Top of brain: movement Front of brain: thinking DR. J. K. ROY 44 CEREBRAL HEMISPHERES Lobes: under bones of same name Frontal Parietal Temporal Occipital Plus: Insula (buried deep in lateral sulcus) DR. J. K. ROY 45 HOMUNCULUS – “LITTLE MAN” Body map: human body spatially represented Where on cortex; upside down DR. J. K. ROY 46 PREFRONTAL CORTEX: COGNITION This area is remodeled during adolescence until the age of 25 and is very important for well-being; it coordinates the brain/body and inter-personal world as a whole Intellect Abstract ideas Judgment Personality Impulse control Persistence Complex Reasoning Long-term planning Social skills Appreciating humor Conscience Mood Mental flexibility Empathy Executive functioning e.g. multiple step problem solving requiring temporary storage of info (working memory) DR. J. K. ROY 47 RETICULAR FORMATION Runs through central core of medulla, pons and midbrain Reticular activating system (RAS): keeps the cerebral cortex alert and conscious Some motor control DR. J. K. ROY 48 THE END OF PHYSIOLOGY OF HUMAN BRAIN & NERVOUS SYSTEM DR. J. K. ROY 49 Biomedical signals: Origins and dynamic characteristics DR. J. K. ROY 50 BIOMEDICAL SIGNALS: ORIGIN AND DYNAMIC CHARACTERISTICS 51 NEURONS AND SYNAPSES Types of Neurons Sensory Motor Interneurons 52 SENSORY NEURONS • INPUT From sensory organs to the brain and spinal cord. Drawing shows a somatosensory neuron Vision, hearing, taste and smell nerves are cranial, not spinal Sensory Neuron Brain Spinal Cord 53 MOTOR NEURONS • OUTPUT From the brain and spinal cord To the muscles and glands. Sensory Neuron Brain Spinal Cord Motor Neuron 54 INTERNEURONS Interneurons carry information between other neurons only found in the brain and spinal cord. Sensory Neuron Brain Spinal Cord Motor Neuron 55 STRUCTURES OF A NEURON 56 THE CELL BODY Contains the cell’s Nucleus Round, centrally located structure Contains DNA Controls protein manufacturing Directs metabolism No role in neural signaling 57 DENDRITES • Information collectors • Receive inputs from neighboring neurons • Inputs may number in thousands • If enough inputs the cell’s AXON may generate an output 58 DENDRITIC GROWTH • Mature neurons generally can’t divide • But new dendrites can grow • Provides room for more connections to other neurons • New connections are basis for learning 59 AXON The cell’s output structure One axon per cell, 2 distinct parts tubelike structure branches at end that connect to dendrites of other cells 60 MYELIN SHEATH • White fatty casing on axon • Acts as an electrical insulator • Not present on all cells • When present increases the speed of neural signals down the axon. Myelin Sheath 61 HOW NEURONS COMMUNICATE Neurons communicate by means of an electrical signal called the Action Potential Action Potentials are based on movements of ions between the outside and inside of the cell When an Action Potential occurs a molecular message is sent to neighboring neurons DR. J. K. ROY 62 PLASMA MEMBRANE FUNCTION OF PLASMA MEMBRANE • Oxygen, carbon di oxide and water can easily cross plasma membrane • large molecule and ions only can move through protein channel 63 WATER + ,Cl- outside Na+ 10 ------= ---K+ 1 Na+ 1 ------= ---K+ 30 WATER + ,Cl- K Inside Cell membrane Inside Cell membrane K 108 mM Cata ions 12mM Na+ 125mM K+ 5mM Cloutside Intra-cellular Fluid Extra-cellular Fluid 120mM Na+ 5mM K+ 125mM Cl- 64 ION CONCENTRATIONS Outside of Cell K+ Na+ Cl- Cell Membrane in resting state K+ Na+ Cl- Inside of Cell ADR. J. K. ROY 65 THE CELL MEMBRANE IS SEMIPERMEABLE K+ Na+ Cl- Outside of Cell Cell Membrane at rest K+ Na+ Cl- - 70 mv A- Inside of Cell Potassium (K+) can pass through to equalize its concentration Sodium and Chlorine cannot pass through Result - inside is negative relative to outside DR. J. K. ROY 66 RESTING POTENTIAL -90mV (a) Polarized Cell • At rest the inside of the cell is at -70 milli volts • With inputs to dendrites inside becomes more positive • if resting potential rises above threshold an action potential starts to travel from cell body down the axon • Figure shows resting axon being approached by an AP 67 DEPOLARIZATION AHEAD OF AP -90mV (a) De-polarized Cell • AP opens cell membrane to allow sodium (NA+) in • inside of cell rapidly becomes more positive than outside • this depolarization travels down the axon as leading edge of the AP 68 REPOLARIZATION FOLLOWS • After depolarization potassium (K+) moves out restoring the inside to a negative voltage • This is called repolarization • The rapid depolarization and repolarization produce a pattern called a spike discharge 69 FINALLY, HYPERPOLARIZATION • Repolarization leads to a voltage below the resting potential, called hyperpolarization • Now neuron cannot produce a new action potential • This is the refractory period 70 RESTING POTENTIAL • Recall the definition of VM from the muscle lectures. • Neurons are also highly polarized (w/ a VM of about – 70mV) due to: »Differential membrane permeability to K+ and Na+ »The electrogenic nature of the Na+/K+ pump »The presence of intracellular impermeable anions • Changes in VM allow for the generation of action potentials and thus informative intercellular communication. DR. J. K. ROY 71 GRADED POTENTIALS Let’s consider a stimulus at the dendrite of a neuron. The stimulus could cause Na+ channels to open and this would lead to depolarization. Why? However, dendrites and somata typically lack voltage-gated channels, which are found in abundance on the axon hillock and axolemma. So what cannot occur on dendrites and somata? Thus, the question we must answer is, “what does this depolarization do?” DR. J. K. ROY 72 GRADED POTENTIALS The positive charge carried by the Na+ spreads as a wave of depolarization through the cytoplasm (much like the ripples created by a stone tossed into a pond). As the Na+ drifts, some of it will leak back out of the membrane. What this means is that the degree of depolarization caused by the graded potential decreases with distance from the origin. DR. J. K. ROY 73 GRADED POTENTIALS Their initial amplitude may be of almost any size – it simply depends on how much Na+ originally entered the cell. If the initial amplitude of the GP is sufficient, it will spread all the way to the axon hillock where V-gated channels reside. If the arriving potential change is suprathreshold, an AP will be initiated in the axon hillock and it will travel down the axon to the synaptic knob where it will cause NT exocytosis. If the potential change is subthreshold, then no AP will ensue and nothing will happen. DR. J. K. ROY 74 NERNST POTENTIAL The chemical potential gradient due to different concentrations between inside and outside of the cell is given by NERNST RELATION ENS = NERNST POTENTIAL = 61.6 Where u-v u+v u = Mobility of cataions ( Negative ions) v = Mobility of Anaions (Positive ions) DR. J. K. ROY 75 ELECTRICAL EQUIVALENT CIRCUIT OF CELL MEMBRANE Inside of the cell 1 KΩ RK 38 KΩ C R Na R Nad 1 50KΩ EK 91mV EK = 61.6 log (30/1) = 91 mV Nernst Potential when Polarized E na = 61.6 log (10/1) = 62 mV Nernst Potential when Depolarized E Na 62mV Out side of the cell C = Capacitance of the Cell RK = Relative permeability of the membrane to the flow of K+ ion R Na = Relative permeability of the membrane to the flow of Na+ ion at polarized condition R Nad =Relative permeability of the membrane to the flow of Na+ ion at De-polarized condition Net K Current + Net Na Current = 0 Net K Gradien Net na Gradient + = RK Rna EK + EC -Ena + EC + =0 RK Rna DR. J. K. ROY 76 ACTION POTENTIALS If VM reaches threshold, Na+ channels open and Na+ influx ensues, depolarizing the cell and causing the V M to increase. This is the rising phase of an AP. Eventually, the Na+ channel will have inactivated and the K+ channels will be open. Now, K+ effluxes and repolarization occurs. This is the falling phase. K+ channels are slow to open and slow to close. This causes the VM to take a brief dip below resting VM. This dip is the undershoot and is an example of hyperpolarization. DR. J. K. ROY 77 DR. J. K. ROY 78 NA+ CHANNELS 1 They have 2 gates. At rest, one is closed (the activation gate) and the other is open (the inactivation gate). Suprathreshold depolarization affects both of them. 2 DR. J. K. ROY 79 3 4 5 DR. J. K. ROY 80 ABSOLUTE REFRACTORY PERIOD During the time interval between the opening of the Na+ channel activation gate and the opening of the inactivation gate, a Na+ channel CANNOT be stimulated. This is the ABSOLUTE REFRACTORY PERIOD. A Na+ channel cannot be involved in another AP until the inactivation gate has been reset. This being said, can you determine why an AP is said to be unidirectional. What are the advantages of such a scenario? DR. J. K. ROY 81 RELATIVE REFRACTORY PERIOD Could an AP be generated during the undershoot? Yes! But it would take an initial stimulus that is much, much stronger than usual. WHY? This situation is known as the relative refractory period. Imagine, if you will, a toilet. When you pull the handle, water floods the bowl. This event takes a couple of seconds and you cannot stop it in the middle. Once the bowl empties, the flush is complete. Now the upper tank is empty. If you try pulling the handle at this point, nothing happens (absolute refractory). Wait for the upper tank to begin refilling. You can now flush again, but the intensity of the flushes increases as the upper tank refills (relative refractory) DR. J. K. ROY 82 In this figure, what do the red and blue box represent? VM TIME DR. J. K. ROY 83 SOME ACTION POTENTIAL QUESTIONS What does it mean when we say an AP is “all or none?” Can you ever have ½ an AP? How does the concept of threshold relate to the “all or none” notion? Will one AP ever be bigger than another? Why or why not? DR. J. K. ROY 84 ACTION POTENTIAL CONDUCTION If an AP is generated at the axon hillock, it will travel all the way down to the synaptic knob. The manner in which it travels depends on whether the neuron is myelinated or unmyelinated. Unmyelinated neurons undergo the continuous conduction of an AP whereas myelinated neurons undergo saltatory conduction of an AP. DR. J. K. ROY 85 CONTINUOUS CONDUCTION Occurs in unmyelinated axons. In this situation, the wave of de- and repolarization simply travels from one patch of membrane to the next adjacent patch. APs moved in this fashion along the sarcolemma of a muscle fiber as well. Analogous to dominoes falling. DR. J. K. ROY 86 SALTATORY CONDUCTION Occurs in myelinated axons. Saltare is a Latin word meaning “to leap.” Recall that the myelin sheath is not completed. There exist myelin free regions along the axon, the nodes of Ranvier. DR. J. K. ROY 87 DR. J. K. ROY 88 RATES OF AP CONDUCTION 1. Which do you think has a faster rate of AP conduction – myelinated or unmyelinated axons? 2. Which do you think would conduct an AP faster – an axon with a large diameter or an axon with a small diameter? The answer to #1 is a myelinated axon. If you can’t see why, then answer this question: could you move 100ft faster if you walked heel to toe or if you bounded in a way that there were 3ft in between your feet with each step? The answer to #2 is an axon with a large diameter. If you can’t see why, then answer this question: could you move faster if you walked through a hallway that was 6ft wide or if you walked through a hallway that was 1ft wide? DR. J. K. ROY 89 NEURON TO NEURON • Axons branch out and end near dendrites of neighboring cells • Axon terminals are the tips of the axon’s branches • A gap separates the axon terminals from dendrites • Gap is the Synapse Dendrite Axon Cell Body 90 SYNAPSE • Sending Neuron axon terminals contain small storage sacs called synaptic vesicles 91 Axon Terminal Synapse vesicles contain neurotransmitter molecules 91 NEUROTRANSMITTER RELEASE Action Potential causes vesicle to open Neurotransmitter released into synapse Locks onto receptor molecule in postsynaptic membrane 92 LOCKS AND KEYS Neurotransmitter molecules have specific shapes Receptor molecules have binding sites When NT binds to receptor, ions enter positive ions (NA+ ) depolarize the neuron negative ions (CL-) hyperpolarize 93 SOME DRUGS WORK ON RECEPTORS • Some drugs are shaped like neurotransmitters • Antagonists : fit the receptor but poorly and block the NT – e.g. beta blockers Agonists : fit receptor well and act like the NT e.g. nicotine. 94 THE END OF MODULE -1 DR. J. K. ROY 95