Nobel Prize (1895): in Physiology or Medicine Schémata zpracovalo Servisní středisko pro e-learning na MU http://is.muni.cz/stech/ Life is a dynamic system with focused behavior, with autoreproduction, characterized by flow of substrates, energies and information. PHYSIOLOGY •Science about living systems (Fernel, 1642) •Experimental science (W. Harvey, 1643; C. Bernard, J.E. Purkyně) 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) PHYSIOLOGY – science about functions (dynamics) • General • Special • Comparative • Evolutional • Applied medical normal (normative) pathological clinical • FUNCTIONAL ORGANISATION OF THE BODY • EXCHANGE AND TRANSPORT OF COMPOUNDS • INTERCELLULAR CONTACTS AND SIGNALLING Functions are studied at 5 levels: molecular, cellular, tissue, organ, organism STRUCTURE AND FUNCTIONS OF CELL, ORGANELLES Molecular biology of the cell. B. Alberts et al., Garland Science 2002 ligand hydrophilic glycocalyx ion hydrophobic I – integral protein R – receptor E – enzyme K – channel P – pump (ATP-ase) Membrane molecules Protein molecules PLASMATIC MEMBRANE 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 BODY FLUIDS BODY COMPOSITION Water 60% (80-50%) of body mass Proteins 18% Lipids 15% Minerals 7% 152 5 2 117 27 0 0 14 157 30 5 10 74 113 0 20 40 60 80 100 120 140 160 mEq/l Concentration of cations and anions in body fluids Extracelulárně Intracelulárně Na K Ca Cl HCO3 Prot. PO4 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 compound. It depends on solubility in water and lipids. OSMOSIS Transport of water across semipermeable membrane in direction to higher concentration of diluted compound (e.g. in direction to lower concentration of water). It depends on number of particles. Osmolarity x osmolality Iso-, hyper-, hypotonicity Oncotic pressure FILTRATION Movement of solvent as a result of osmotic and hydrostatic pressure. Production and resorption of interstitial fluid (Starling forces). 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, AMK Ca2+, H+ Na+/K+ ATP-ase (exchanger) Similar transports: •Ca2+/H+ •Na+/K+ •K+/H+ •Na+/H+ AGAINST concentration gradient ACTIVE TRANSPORTS ligand hydrophilic glycocalyx ion hydrophobic I – integral protein R – receptor E – enzyme K – channel P – pump (ATP-ase) Membrane molecules Protein molecules PLASMATIC MEMBRANE IONIC CHANNEL Molecular biology of the cell. B. Alberts et al., Garland Science2002 Membránová elektrofyziologie myokardu, P. Pučelík, Avicenum, 1990 GATING G-proteinsMolecular biology of the cell. B. Alberts et al., Garland Science2002 Molecular biology of the cell. B. Alberts et al., Garland Science2002 K+ ClSIGMA RBI, www.sigma-aldrich.com Repolarisation reserve Na+ SIGMA RBI, www.sigma-aldrich.com Ca+ SIGMA RBI, www.sigma-aldrich.comL, T, N type COMMUNICATION BETWEEN 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. INTEGRATION OF HUMOURALAND NERVOUS SYSTEMS: • synapse • hypothalamus - pituitary gland • adrenal medulla 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.) 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). 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 DISTURBANCES IN BODY FLUIDS • Communication with surroundings lungs, GIT, kidneys, skin • Internal sources of instability metabolism Extracellular fluids represent transport systems BASIC TYPES OF FEEDBACK SERIAL PARALLEL NEGATIVE DIRECT NEGATIVE INDIRECT FEEDBACK NEGATIVE POSITIVE Deviation from desired value oscillates or continuously increases. POSITIVE FEEDBACK RARE !!! PHYSIOLOGICAL ensuring of systems, activation PATHOLOGICAL Instability - death BASIC FEATURES OF REGULATORY SYSTEMS • System is stabile at least within the range of its functional range • Not a single real regulatory system regulates ideally • Regulatory time = time till the moment, when regulated parameter returns to its original (resting) values VICIOUS CIRCLE AND DEATH BLEEDING  FILLING OF THE HEART   CARDIAC OUTPUT BP   CORONARY FLOW    CONTRACTILITY    CARDIAC OUTPUT BP   CORONARY FLOW    CONTRACTILITY  0 1 2 3 4 5 Cardiacoutput bleeding Regulation - feedback Vicious circle + feedback