Introduction to Biomedical Science PDF

의료인공지능 융합인재양성 사업 Introduction to Biomedical Science - 의과학의 이해 - Dept of Physiology Ajou University School of Medicine Introduction to Biomedical Science (의과학의 이해) 주별 날짜 강의내용 학점/시간 담...

의료인공지능 융합인재양성 사업 Introduction to Biomedical Science - 의과학의 이해 - Dept of Physiology Ajou University School of Medicine Introduction to Biomedical Science (의과학의 이해) 주별 날짜 강의내용 학점/시간 담당교수 1 9/3 강좌소개 및 오리엔테이션/ 인체해부생리- 개념 및 체성조절 3 이수환 2 9/10 인체해부생리- 전기 조절과 신경계 (운동) 3 백은주 3 9/17 개천절 4 9/24 인체해부생리- 근육/심혈관계, 심전도 3 이수환 5 10/1 인체해부생리- 호흡계/자율신경계 조절 백은주 6 10/8 인체해부생리- 소화기계/내분비계 3 이수환 7 10/15 인체해부생리- 신장비뇨기계, 신경계(일반감각) 3 백은주 8 10/22 질병의 이해- 병리총론 3 남지해 9 10/29 인체해부생리- 신경계(특수감각), 뇌의 고위기능, 뇌파 3 백은주 10 11/5 중간고사 3 백은주 11 11/12 의료데이터 3 박래웅 12 11/19 유전체 정밀의학 3 우현구 13 11/26 유전체의학-유전체자료 (NGS) 3 김규태 14 12/3 임상데이터 및 임상의학의 이해 3 정재연 15 12/10 인공지능 신약개발 3 조성권 16 12/17 기말고사 우현구  Natural Science Living Body Nonliving Body Biology Morphology Functionology  Anatomy  Physiology  Histology  Pathology  Cytology…  Pharmacology  Biochemistry… Why Study Two Disciplines at One Time? Form and function are so tightly linked  Without some knowledge of form, we cannot understand function A study of anatomy alone does not allow one the satisfaction that comes from actually understanding the body. Physiology cannot be learned without some knowledge of basic anatomy. The Organ System System Representative Organs/Structures Representative Functions 1. Skeletal system Bones, joints, marrow Support, protection, leverage for movement, hematopoiesis (blood formation) 2. Muscular system Skeletal muscles, tendons Movement, posture, heat production 3. Nervous system Brain, spinal cord, nerves, sense organs Regulation of body activities 4. Endocrine system All hormone producing glands, i.e., Regulation of body activities pituitary, adrenal, pancreas 5. Reproductive system Ovaries, testes, vagina, penis, associated Reproduction ducts and structures 6. Cardiovascular system Heart, blood vessels Transportation of gases, nutrients, and wastes 7. Respiratory system Lungs and associated airways Exchange of gases between the internal and external environment 8. Digestive system Esophagus, stomach, intestines, Ingestion, digestion, and absorption of associated glands nutrients, elimination of wastes 9. Urinary system Kidneys, urinary bladder, ureters, urethra Elimination of wastes, regulation of blood composition 10. Integumentary system Skin, sweat glands, hair follicles Protection, temperature regulation 11. Immune system White blood cells, bone marrow, lymph Protection nodes, thymus Introduction to Human Anatomy and Physiology  Anatomical Terminology  Basis of Physiology: Homeostasis  Membrane Structure/Membrane Transport  Biological Communication: Humoral Control Anatomical Terminology - 해부학 용어의 기초 - Dept of Physiology Ajou University School of Medicine What is Anatomy?  It is the science which deals with the study of the structure, shape of the body & body parts, and their relationships to one another (생물체 또는 생물체를 구성하고 있는 각 부위의 구조와 형태, 그리고 각각의 상호관계 등을 연구하는 학문)  Gross Anatomy (육안해부학, 맨눈해부학)  Microscopic Anatomy (현미해부학; Histology: 조직학)  Developmental Anatomy (Embryology: 발생학)  Applied Anatomy, Clinical Anatomy, Radiological Anatomy… Why Anatomical Language?  To prevent misunderstanding, a special set of terms are used to describe the identification and location of body structures : ‘정확한 용어’를 사용해야 정확한 의도를 전달할 수 있다. (You have to use the correct terminology to convey the correct intentions) The Language of Anatomy (Anatomical Terminology) To accurately describe body parts, the body is in a standard position called the Anatomical Position (해부학적 자세) in which:  Body is erect  Arms hanging by the side  Palms facing forward  Feet are parallel Locational(Directional) Terminology (위치에 관한 용어)  상대정맥 (上大靜脈) 하대정맥 (下大靜脈)  원위세뇨관 (遠位細尿管) 후각 근위세뇨관 (後角) (近位細尿管) 전각 (前角) 외측 회색질 (外側 灰色質) 내측 회색질 (內側 灰色質)  Locational Terminology Term Definition Example Medial (안쪽) Toward the midline of the body Your nose is medial to your eye. (Your nose is nearer to the middle than your eye.) Lateral (바깥쪽) Away from the midline of the body Your ear is lateral to your eye. (Your ear is further away from your midline than your eye.) Intermediate (중간) Between two structures Your eye is intermediate to your nose and your ear. (It is between your nose and ear.) Anterior (앞쪽) Toward the front surface of your body Your nose is an anterior structure. (It is on your front surface.) Posterior (뒤쪽) Toward the rear surface of your body Your kidneys are posterior to your intestine. (They are behind your intestines.) Ventral (배쪽) Toward the front surface of your body Your navel is a ventral structure. (It is located on your front surface.) Dorsal (등쪽) Toward the rear surface of your body Your spinal cord is a dorsal structure. (It is toward your back surface.) Superior (위) Above or higher than Your head is superior to your neck. (Your head is above your neck.) Inferior (아래) Below or lower than Your chest is inferior to your neck. (Your chest is below your neck.) Superficial (표면쪽) Toward the surface of your body Your skin is superficial to your muscles. (Your skin is closer to the surface than your muscles are.) Deep (깊은쪽) Away from the surface Your brain is deep to your skull. (Your brain is further from the surface than your skull is.) Ipsilateral (같은쪽) Same side Your right ear is ipsilateral to your right eye. Contralateral (반대쪽) Opposite side Your left ear is contralateral to your right eye. Proximal (가까운쪽)* Closer to the beginning or site of Your elbow is proximal to your wrist. (Your elbow is closer to the attachment of your arm attachment to your trunk than your wrist is.) Distal (먼쪽)* Further from the beginning or site of Your colon is distal to your small intestines. (The digestive tract is a tubular structure; the attachment colon is further from the beginning of the tube than the small intestine is.) Parietal (벽쪽) Visceral (내장쪽) * Terms used in tubular structure or in the limbs.  Planes of Section (해부학적 자세에서의 절단면) The body has Three Imaginary Planes (sections) that lie at right angles to one another (in the anatomical position).  Frontal (coronal) plane (관상면, 冠状面)  Sagittal plane (시상면, 矢狀面)  Transverse (horizontal) plane (수평면, 水平面) Frontal = Front View Sagittal = Side View Transverse = Top View  Plane of section (절단면) - determine the direction of observation (관찰하고 있는 방향을 결정) - important for understanding the internal structure of the organ (기관의 내부구조를 이해하는데 중요)  Body Cavities (몸공간; 체강 體腔) - Spaces occupied by organs (기관들이 차지하고 있는 공간) 1. Dorsal cavity (등쪽공간)  Cranial cavity (머리뼈공간; 두개강 頭蓋腔): 뇌 (brain)  Vertebral cavity (Spinal cavity; 척주관 脊柱管): 척수 (脊髓 spinal cord) 2. Ventral cavity (배쪽공간)  Thoracic cavity (가슴안; 흉강 胸腔): 횡격막위 (superior to diaphragm) - Pleural cavity (흉막강 胸膜腔): 폐 (lung) - Mediastinum (가슴세로칸, 종격동 縱隔洞): 두 개의 흉막강 사이; 식도 (esophagus), 기도 (trachea) - Pericardial cavity (심낭강 心囊腔): 심장 (heart)  Abdominopelvic cavity (배골반안, 복골반강 腹骨盤腔) : 횡격막아래 (inferior to diaphragm) - Abdominal cavity (배안; 복강 腹腔): 위 (stomach), 창자 (intestines), 간 (liver), 이자 (pancreas) - Pelvic cavity (골반강 骨盤腔): 생식기관 (reprod. organs), 방광 (bladder) Serous membrane (serosa, 장막 漿膜) - a smooth tissue membrane of mesothelium lining the contents and inner walls of body cavities (각 몸공간과 이 안에 들어 있는 기관들을 덮고 있는 막) * Serous fluid (장액): allow lubricated sliding movements between opposing surfaces (윤활작용) - actually one continuous membrane (공간벽을 덮고 있는 막은 기관표면을 덮고 있는 막과 연속되어 있음) - Each serosa has a unique name (각 장막에는 고유의 이름이 명명되어 있음) ex) pleura (흉막): pleural cavity (흉막강); peritoneum (복막): 배골반안 (abdominopelvic cavity) (내장쪽심장막) (심낭) (벽쪽심장막) Basis of Physiology: Homeostasis - 생리학의 기초: 항상성의 원리- Dept of Physiology Ajou University School of Medicine  What is Physiology? Physiology: Physiologia (L) Physis (nature) + logia → Knowledge of Nature Hippocrates (460-377 BC): the healing power of nature Aristotle (384-322 BC): functioning of all living organisms Fernel (1542) → the study of the vital functions of the human body →The study of identifying the individual functions of the cells and organs that make up the human body, the integrated functions they correlate and control, that is, the mechanism by which the human body’s individual activity and homeostasis are expressed (인체를 구성하는 세포와 기관들의 개별적인 기능과 그들이 상호 연관, 조절되어 나타내는 통합적인 기능 즉, 인체의 개체활성과 항상성이 발현되는 기전을 규명하는 학문)  Classification of Human Physiology Cell Physiology (세포생리학) - 세포단위에서 일어나는 물질 교환과 운반, 에너지 변환, 신호전달 등의 기전 (submolecular, molecular, and cell level) Organ Physiology (기관생리학) - 기관별 기능 및 이를 통합, 조절하는데 관여하는 신경, 내분비계의 기능 Pathophysiology (병태생리학) - 정상 생리상태에서 질병으로 전이되는 기전 “Physiology focuses on mechanisms of action” Why and How Mechanistic approach (기계론적 접근법) vs Teleological approach (목적론적 접근법) I. Characteristics of the Life and Homeostasis 1. Characteristics of the Life (생명체의 특징) 1) Reproduction (생식) 2) Growth (성장) 3) Movement (운동) 4) Adaptation (적응) 5) Metabolism (대사) - catabolism (이화작용) - anabolism (동화작용) 6) Organization (유기적 체제) - interdependence (상호의존) - interaction (상호작용)  The essential conditions for livings things to sustain life while maintaining order in the body - transformation of energy (에너지 변환) - transport of materials (물질운반) The integration between systems of the body Physiology is an Integrative Science 2. Concept of Homeostasis 1) Homeostasis (항상성; Gr. “staying the same”) Homeostasis: homeo means “the same”; stasis means “to stand or stay” - The Foundation of Physiology!  W.B. Cannon (20c American physiologist) - State of relative stability of the body's internal environment; requires coordinated physiological processes (인체의 내적환경이 상대적으로 일정하게 유지되는 상태로서, 세밀하게 연관된 생리적 조절과정을 필요로 한다) 2) Internal Environment (인체의 내적환경)  Claude Bernard (19c French physiologist) - the environment surrounding each cell: theoretical physiological concept - Extracellular Fluid(내해; internal sea): anatomical terms; interstitial fluid, plasma - Multicellular organism can survive only as long as it is able to maintain the composition of its internal environment in a state compatible with the survival of its individual cells  Factors homeostatically regulated 1. Concentration of nutrient molecules 2. Concentration of O2 and CO2 3. Concentration of waste products 4. pH 5. Concentration of water, salt, and other electrolytes 6. Temperature 7. Volume and pressure 3) Interdependent relationship of cells, body systems, and homeostasis - serve as the foundation for modern physiology “Homeostasis is essential for the survival of each cell, cells make up body system, and body systems maintain homeostasis” maintain Body Systems Homeostasis make up Cells is essential for the survival of  Contributions of the body systems to homeostasis - The 11 body systems contribute to homeostasis in own (important) ways. - The body is a coordinated whole even though each system provides its own special contributions. - The functioning whole is greater than the sum of its separate parts. * specialization, cooperation, interdependence “A cell or even 2.a Homeostatic randomControl Systems combination of cells, obviously cannot create an artistic masterpiece or design a spacecraft, but body cells working together permit those capabilities in an individual.” 팀보다 위대한 선수는 없다! 4) Homeostatic mechanisms - Minimize change (state of relative stability): dynamic steady state cf. Steady state (항정상태): requires energy to maintain variable constant Equilibria (평형상태): no input of energy is required to maintain the constancy  Steady state  Equilibria a) Homeostatic Control Systems  Minimum required element for Homeostatic Control Systems (최소 구비요소 ) (1) Detectors (감지기): neurons, macula densa (2) Effectors (효과기): muscle, gland, circulating system, urinary system (3) Coordinating and integrating system (연계 및 통합; 통합중추): nervous system, endocrine system * 설정치 (Set point; Operating point)  General Characteristics of Homeostatic Control System Feedback system (되먹임 기전) ‧ Negative-feedback system (음성되먹임): the most common homeostatic mechanism ‧ Positive feedback system (양성되먹임): does not favor stability cf) feedforward regulation Negative-feedback system * Antagonistic effectors (길항작용 효과기): more stringent and more efficient adjustment * Normal range (정상범위): being constant is dynamic and relative, not absolute  Positive-feedback system cf) Feedforward regulation: eg. mouthwatering 5) Processes related to homeostasis - Adaptation, acclimatization, biological rhythms a) Adaptive System (adaptation, 적응) - a characteristic that favors survival in specific environment ex. homeostatic system: an example of genetically endowed biological adaptation b) Acclimatization (환경순응) - an environmentally induced improvement in the functioning of an already existing genetically based homeostatic system (no change in genetic endowments)  reversible acclimatization (가역적 순응): e.g. heat acclimatization  irreversible acclimatization (비가역적 순응): developmental acclimatization (e.g. barrel-shaped chest) Barrel-shaped chest c) Biological Rhythms (생체리듬) - Circadian rhythm: app. 24hrs; wake-sleep cycles, body temperature, hormone secretion; internally driven: Entrainment(동조화), range of entraining: 23 - 27 h - Phase-shift rhythms (위상이동 리듬): reset internal clock (e.g. Jet lag)  -Feedback System-Error Signal Architecture of the Circadian System  -Feedback System-Error Signal Circadian Alignment vs Misalignment Metabolic Dysfunction 3. Aging and Homeostasis Aging is associated with a decrease in the number of cells in the body, due to some combination of decreased mitosis and increased cell death, and to malfunction of many of the cells that remain. Physiologic Limit Limit beyond which homeostasis cannot be restored Physiologic Reserves Homeostasis being restored Increasing Age Physiologic reserves allows us to With homeostasis, an insult that may maintain homeostasis in the be withstood in a younger person pushes presence of environmental, the elderly beyond their functional emotional or physiological stress capacity, causing decompensation, disease or death 3. Aging and Homeostasis Aging is associated with a decrease in the number of cells in the body, due to some combination of decreased mitosis and increased cell death, and to malfunction of many of the cells that remain. Physiologic Limit Limit beyond which homeostasis cannot be restored Physiologic Reserves Homeostasis being restored Increasing Age Physiologic reserves allows us to With homeostasis, an insult that may maintain homeostasis in the be withstood in a younger person pushes presence of environmental, the elderly beyond their functional emotional or physiological stress capacity, causing decompensation, disease or death 4. Stress and Homeostasis Stress: the overall disruption that forces the body to make adaptive changes ; causes non specific response of the body Stressor: physical (heat, noise), chemical (food, hormones), microbiological (viruses, bacteria), physiological (tumor, abnormal functions), developmental (old age, genetic changes), psychological (emotional and mental disturbances) - all stressors have one thing in common: they increase the demand for adjustment. Adaptability - the base for homeostasis and of resistance to stress - probably the most distinctive characteristic of life - great capacity for adaptation is the basis for maintaining homeostasis and resistance to stress → Some amount of stress is normal and may actually be beneficial - Long-term stress decreases the effectiveness of immune system - When stress is greater than the corrective feedback systems, it is considered to be an injury that may lead to disease, disability, or even death. General Adaptation Syndrome General Adaptation Syndrome - Hans Selye (1970)  Alarm Response  Adaptation  Exhaustion Normal level of resistance Membrane Structure/Membrane Transport - 세포막의 구조/세포막을 통한 물질수송 - Dept of Physiology Ajou University School of Medicine I. Functions of Plasma Membrane 1. Regulate the passage of substances into and out of the cell 2. Detect chemical messengers arriving at the cell surface 3. Link adjacent cells together by membrane junction 4. Anchors a variety of proteins II. Membrane Structure Lipid bilayer (지질 이중층 구조): relatively impermeable barrier to the passage of most water-soluble molecules Fluid-Mosaic Model (Singer and Nicholson, 1972) 1. Chemical Components of Membrane 1) Membrane Lipids: amphipathic molecule  phospholipid (인지질)  cholesterol (콜레스테롤)  glycolipid (당지질) 2) Membrane Proteins  Integral or intrinsic protein/ Peripheral or extrinsic protein  Functions of membrane proteins - transport specific molecules - catalyzing membrane associated reactions - connect the membrane to cytoskeleton, extracellular matrix, or adjacent cells - receptors to detect and transduce chemical signal 3) Carbohydrates on the Surface of the Membrane  Cell surface is coated with sugar residues: glycocalyx - hydrophilic structure - unequal distribution between the two layers - serve as specific membrane receptors for extracellular messengers - important factor in cell-to-cell recognition process III. Membrane Transport 1. Why Membrane Transport? 2. Types of Movement through the Membrane 1) Passive transport (수동적 운반) simple diffusion (단순확산) facilitated diffusion (촉진적 확산) 2) Active transport (능동적 수송) primary active transport (1차 능동수송) secondary transport (2차 능동수송) 3) Bulk transport (집단수송): vesicular transport (소포운반) endocytosis (세포내 이입): pinocytosis (음작용), phagocytosis (식작용) exocytosis (세포외 유출) Biological Communication: Humoral Control - 생물학적 정보전달: 체액성 조절 - Dept of Physiology Ajou University School of Medicine Cell-cell communication Signaling by plasma-membrane bound molecules Juxtacrine (contact-dependent) Signaling by secreted molecules Autocrine Paracrine Synaptic (neurotransmitter) Endocrine (hormone) Electrical Signaling Endocrine System Nervous System Endocrine cells release hormones Neurons release neurotransmitters Hormones travel to another nearby A neurotransmitter acts on specific cell or act on cell in another part of cell right next to it the body. The effects of hormones can last The effects of neurotransmitters are hours, or days short-lived (within milliseconds) Regulates long term-ongoing Performs short term-crisis metabolic function management Receptor Mediated Signaling Plasma membrane receptor mechanism  Receptor Mediated Signaling Plasma membrane receptor mechanism 1. Ion channel-linked receptors 2. G-protein-coupled receptors 3. Adenylate cyclase mechanism 4. IP3 mechanism 5. Ca2+-calmodulin mechanism 6. Arachidonic acid system 7. Gaseous second messenger system 8. Others: kinase receptors and kinase-associated receptors Nuclear or cytosolic receptor mechanism 1. Ion channel-linked receptor Neurotransmitter Receptor 1) Directly gated channel - Ionotropic receptors (이온성 수용기) ex) ACh(Nicotinic R), GABA, AMPA, NMDA - fast synaptic action, lasting only ms - motor neuron (neuromuscular junction) - produce behavior 2) Indirectly gated channel - Metabotropic receptors (대사성수용기) ex) NE, ACh(Muscarinic R) - slow synaptic action - autonomic nervous system (adrenergic, cholinergic N) - modulate behavior Plasma membrane receptor mechanism Ligand Receptor Transducer Cell Membrane Second messenger generator Desensitization Second messenger Effector systems 2. G-protein-coupled receptors GAP: GTPase activating protein GEF: guanine nucleotide exchange factor  Four Families of Heterotrimeric G Proteins SOME FAMILY SUBUNITS THAT FAMILY SOME FUNCTIONS MEMBERS MEDIATE ACTION I Gs  activates adenylyl cyclase; activates Ca2+ channels Golf  activates adenylyl cyclase in olfactory sensory neurons II Gi  inhibits adenylyl cyclase  activates K+ channels Go  activates K+ channels; inactivates Ca2+ channels  and  activates phospholipase C- Gt (transducin)  activates cyclic GMP phosphodiesterase in vertebrate rod photo receptors III Gq  activates phospholipase C- IV G12/13  activates Rho family monomeric GTPases (via Rho-GEF) to regulate the actin cytoskeleton * Families are determined by amino acid sequence relatedness of the  subunits. Only selected examples are included. About 20  subunits and at least 6  subunits and 11  subunits have been described in humans. 3. Adenylate cyclase mechanism cAMP-dependent kinase (Protein kinase A; PKA) CREB: cAMP response element binding protein CBP: CREB binding protein 4. IP3 mechanism 5. Ca+2-calmodulin mechanism 6. Arachidonic Acid System ▪ phospholipase A2: liberate AA from phospholipid ▪ eicosanoid: cyclooxygenase, lipoxygenase, cyt P450 metabolites of AA ▪ act as transcellular synaptic messenger: highly lipid soluble and readily diffuse through membranes ▪ prostaglandin receptor: G-protein coupled receptors O H2C O CR1 O R2C O CH O H 2C O P O X A2 O- C D 7. Gaseous second messengers (NO, CO) system - NO: produced by a Ca2+/calmodulin dependent enzyme, NO-synthase, in response to glutamate, apparently acting through NMDA receptors and requiring an influx of Ca2+ ions. - CO: produced by the enzyme heme oxygenase. ▪ NO and CO have distinct three properties  pass through membrane readily  affect nearby cells without acting through a surface receptor  extremely short lives ▪ activate guanylate cyclase → convert GTP to cGMP - two forms of guanylyl cyclase (cGMP production is not directly linked to G-protein activation) · integral membrane protein: extracellular receptor domain and an intracellular catalytic domain · cytoplasmic enzyme: activated by NO ▪ cGMP: directly act on specific ion channel (outer segment of retinal rod cell) or activate cGMP dependent protein kinase ▪ cGMP-dependent kinase (PKG): single polypeptide that contains both regulatory (cGMP-binding) and catalytic domain ex) Purkinje cells of the cerebellum contributes to a synaptic plasticity (motor learning)  Natriuretic NO, CO peptides Soluble Receptor Guanylate Cyclases Guanylate Cyclases cGMP Ion Channels PKG cGMP-regulated PDEs Ion Flux Substrate cAMP↑ or ↓ phosphorylation Ca/CaM 8. Kinase receptors and Kinase-associated receptors Receptor kinases - growth factors (EGF, NGF, BDNF), cytokines & insulin ▪ differences from G-protein coupled receptor 1) span the membrane only once 2) cytoplasmic domain contains protein kinase activity (tyrosine kinase) ▪ monomer or dimers + protein kinase (phosphorylate proteins on tyrosine residues) ▪ adaptor proteins: serve to assemble a multiprotein signaling complex ex) SH2 for phosphotyrosine, SH3 domain for proline-rich regions of effector protein ▪ promote cell survival and regulate cell differentiation and development ▪ shorter-term modulatory actions: modulation of ion channels and control of transmitter or hormone release  Kinase-associated receptors - do not have a tyrosine kinase domain, rather act through cytoplasmic kinases. - cytokines, leptin, erythropoietin receptor STAT: signal transducers and activators of transcriptions JAK: Janus kinase Nuclear or cytosolic receptor mechanism P-box: proximal box; recognize hormone response element D-box: distal box; protein-protein interaction