1 2 PHYSIOLOGY • Science about living systems (Fernel, 1642) • Experimental science (W. Harvey, 1643; C. Bernard, J.E. Purkyně) Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 3 Aims of the course: 1. Learn the terms 2. Learn basic facts 3. Understand functional relations 4. Understand clinical consequences BIOFYSICS BIOCHEMISTRY BIOLOGY MOLECULAR BIOLOGY PHYSIOLOGY PATHOPHYSIOLOGY FUNCTIONAL CLINICAL PREVENTIVE PHARMACOLOGY DIAGNOSTICS SUBJECTS MEDICINE Teaching forms – lecture, seminar, demonstration, practical (lab) Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 4 PHYSIOLOGY – science about functions (dynamics) • General • Special • Comparative • Evolutional • Applied medical normal (normative) pathological clinical Functions are studied at 5 levels: molecular, cellular, tissue, organ, organism Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 5 Structural and functional organisation of the living systems. Homeostasis. 6 Life is a dynamic system with focused behavior, with autoreproduction, characterized by flow of substrates, energies and information. Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 7 STRUCTURE AND FUNCTIONS OF CELL ORGANELLES Molecular biology of the cell. B. Alberts et al., Garland Science 2002Marie Nováková Department of Physiology, Faculty of Medicine, Masaryk University 8 ligand hydrophilic glycocalyx ion hydrophobic I – integral protein R – receptor E – enzyme K – channel P – pump (ATP-ase) Membrane molecules Protein molecules PLASMATIC MEMBRANE Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 9 GIT, lungs, kidney, skin Plasma 5% - 3.5 litres Interstitial 15% - 10.5 litres fluid Intracellular 40% - 28 litres fluid Evans blue, 131J Inulin, manitol, sacharose Antipyrin, D2O Total volume of fluids Extracellular fluid (incl. plasma) COMPARTMENTALISATION OF BODY FLUIDS Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 10 BODY FLUIDS BODY COMPOSITION Water 60% (80-50%) of body mass Proteins 18% Lipids 15% Minerals 7% Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 11 TRANSPORT MECHANISMS ACTIVEPASSIVE DIFFUSION OSMOSIS FILTRATION REGULATED FACILITATED DIFUSION COTRANSPORT SYMPORT ANTIPORT ATP-ases Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 12 PASSIVE TRANSPORT MECHANISMS Differences in body fluids composition result from features of barriers and forces responsible for transport. DIFUSION Transport of gases, substrates, metabolites (up to m.w. 60 thous. in direction of concentration gradient of diluted substance. It depends on its solubility in water and lipids. Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 13 OSMOSIS Transport of water across semipermeable membrane in direction to higher concentration of diluted substance (e.g. in direction to lower concentration of water). It depends on number of particles. Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 14 FILTRATION Movement of solvent as a result of osmotic and hydrostatic pressure. Production and resorption of interstitial fluid (Starling forces). Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 15 REGULATED TRANSPORTS COTRANSPORT transported compound uses concentration gradient of Na+ as the driving force FACILITATED DIFUSION selective carrier limited capacity amino acids phosphate SYMPORT in the same direction ANTIPORT in opposite direction glucose, AA Ca2+, H+ Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 16 Na+/K+ ATP-ase (exchanger) Similar transports: •Ca2+/H+ •Na+/K+ •K+/H+ •Na+/H+ AGAINST concentration gradient ACTIVE TRANSPORTS Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 17 ligand hydrophilic glycocalyx ion hydrophobic I – integral protein R – receptor E – enzyme K – channel (kanál) P – pump (ATP-ase) Membrane lipids Proteins PLASMATIC MEMBRANE Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 18 IONIC CHANNEL Molecular biology of the cell. B. Alberts et al., Garland Science 2002 Membránová elektrofyziologie myokardu, P. Pučelík, Avicenum, 1990 Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 19 GATING Molecular biology of the cell. B. Alberts et al., Garland Science 2002 Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 20 Molecular biology of the cell. B. Alberts et al., Garland Science 2002 Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 21 K+ ClSIGMA RBI, www.sigma-aldrich.com Repolarization reserve Marie Nováková Department of Physiology, Faculty of Medicine, Masaryk University 22 Na+ SIGMA RBI, www.sigma-aldrich.com Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 23 Ca+ SIGMA RBI, www.sigma-aldrich.com L, T, N type Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 24 COMMUNICATION AMONG THE CELLS MECHANICAL CONNECTION • desmosomes (macula adherens; cell adhesion and mechanical stability of tissues) – epidermis, liver, myocardium ELECTRICAL CONNECTION • gap junction (nexus) (in intercalar disc; consists of conexons) HUMORAL CONNECTIONS (REGULATION) • autocrine • paracrine • endocrine • juxtacrine • neurocrine NERVOUS CONNECTIONS (REGULATION) Receptor, ligand, second messenger Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 25 INTEGRATION OF HUMORALAND NERVOUS SYSTEMS • synapse • hypothalamus - pituitary gland • adrenal medulla Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 26 HOMEOSTASIS - MAINTENANCE OF CONSTANT CONDITIONS IN THE INTERNAL ENVIRONMENT REGULATED PARAMETERS: body temperature, volume of body fluids, osmotic pressure, pH, pO2, pCO2, concentration of ions, glycaemia, etc. (isohydria, isovolemia, isoionia, isoosmia, …) IN A BROAD SENSE – in body fluids IN A STRICT SENSE – in particular compartments (blood…..organelles) or maintenance of certain parameter (blood pressure, muscular tension, etc.) Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 27 DISTURBANCES IN HOMEOSTASIS • Communication with surroundings lungs, GIT, kidneys, skin • Internal sources of instability metabolism Extracellular fluids represent transport systems Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 28 REGULATION Control of living systems. Living systems – open systems; their existence depends on flow of energy and substances between organism and environment in both directions. Appears at all levels of system (cell – whole organism). Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 29 ASSOCIATION OF DIFFERENT LEVELS OF REGULATION Systemic regulation – nervous and humoral Local regulation (metabolic) – chemical – pO2, pCO2, pH, prostaglandins Autoregulation myogenic –constant blood flow during changing perfusion pressure in the heart – homeometric and heterometric Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 30 FEEDBACK NEGATIVE POSITIVE Deviation from desired value oscillates or continuously increases. POSITIVE FEEDBACK RARE !!! PHYSIOLOGICAL Ensuring of systems, activation PATHOLOGICAL Instability - death Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University