INTRODUCTION TO THE STUDY OF PHYSIOLOGY
Historical background and the principle of internal environment. Homeostasis. Mechanisms of homeostasis. Control systems, negative and positive feedback, reflex control, feedforward control, biological rhythms.
PHYSIOLOGY OF THE NEURON AND OF THE SYNAPSE
Movement of molecules across biological membranes. The body fluid compartments. The Teorell equation and passive processes: mass flow, Fick's laws and diffusion flow, ion flow in an electric field, permeability, lipophilic and hydrophilic substances.
Membrane transports. Ion channels: permeation mechanisms, selectivity, activation, inactivation and modulation. Patch-clamp and single channel current. Main types of ion channels and their role. Transporter-mediated processes: facilitated diffusion, primary and secondary active transport. Aquaporines. Principles of transport across epithelia. Osmosis.
Neurons and glial cells. Organizational principles of the cellular components of the nervous system. Neurons: axonal transport, fundamental neuronal circuits, organizational levels of neural networks. Functional roles of glial cells: astrocytes, oligodendrocytes, Schwann cells, microglia, radial glia.
Biophysics of excitable membranes. Equivalent electrical circuit model. Diffusion potential. Equilibrium potential and Nernst equation. Donnan equilibrium. Goldman equation. Role of the Na+/K+ pump. Resting potential. Action potential: ionic currents, membrane permeability, single channel currents, all-or-none law, and refractory period. Passive properties of the neuronal membrane and electrotonic propagation: effects of electric currents on the membrane, time constant and space constant. Action potential conduction in unmyelinated fibers: relationship between diameter, space constant and conduction velocity. Saltatory conduction in myelinated fibers. Conduction velocity and nerve fibers classification.
Synaptic transmission. Electrical and chemical synapses. Neuromuscular junction (endplate) and mechanisms of neurotransmitter release: role of Ca2+, miniature endplate potentials, molecular mechanisms of neurotransmitter release, synaptic vesicles cycle. Neurotransmitters: synthesis, storage in vesicles, release, removal by diffusion, reuptake, inactivation. Functional differences between low-weight neurotransmitters and neuropeptides. Neuromodulators and diffuse projection systems. Postsynaptic mechanisms: reversal potential and ionic mechanisms of endplate potential and of excitatory and inhibitory postsynaptic potentials in central synapses. Synaptic signal integration: temporal and spatial summation.
Modulation of neurotransmitter release: postsynaptic membrane potential, post-tetanic potentiation, presynaptic inhibition and facilitation. Membrane receptors for neurotransmitters: functional principles and ionotropic channels and metabotropic G protein-coupled receptors. Synaptic plasticity: LTP, LTD, STDP and homeostatic synaptic plasticity. The experimental model based on the Aplysia of Eric Kandel.
Mechanism of contraction. Sliding of myofilaments within the sarcomere. Tension-length curve of the sarcomere. Crossbridge cycle. Excitation-contraction coupling in skeletal and cardiac muscle fibers: voltage sensor, Ca2+ release channel, removal of Ca2+.
Mechanics of muscle contraction. Tension and load. Isotonic and isometric contraction. Muscle contraction during lengthening. Muscle twitch, summation and tetanus. Factors that control muscle tension. Tension-length curve in the muscle. Velocity-force relationship. Mechanical power.
Muscle energetics. Time course of energy substrates consumption. Muscular fatigue. Slow, rapid-fatigue resistant and fast fatigable skeletal muscle fibres. Control of contraction force in the muscle. Motor units. Recruitment and discharge frequency of motor units.
Physiology of smooth muscle. Differences with striated muscle. Single unit and multiple unit smooth muscle. Contraction mechanism. Electro-mechanical coupling and regulation of contration. Control mechanisms. Crossbridge cycle and "latch" state.
PHYSIOLOGY OF THE CARDIOVASCULAR SYSTEM
General organization and functional anatomy of heart and vessels.
Physiology of cardiac muscle. Comparison of cardiac versus skeletal and smooth muscle: action potential and refractory period, excitation-contraction coupling, mechanical features. Membrane channels and receptors.
The tissues of the heart: cardiac muscle (myocardium), pacemaker cells and conductive tissue. The properties of the heart: chronotropy, dromotropy, inotropy and bathmotropy.
The heart as a pump; the cardiac cycle; cardiac volumes; heart sounds.
Regulation of heart pumping; Intrinsic regulation Starling's law. Preload and afterload. Extrinsic regulation: nervous, humoral and pharmacological regulation. Cardiac work.
Specialized pacemaker, conductive system of the heart and the conduction of the impulse.
Electrophysiology of the heart: the healthy electrocardiogram. Physical bases of electrocardiography (dipole, electric field, conductor of volume and linear conductor), electrocardiographic leads (bipolar, augmented and precordial unipolar leads). Vector analysis and electrocardiographic interpretation. Cardiac arrhythmias and their interpretation.
Biophysics of the circulatory system: arteries, blood capillaries, and veins. Pressure, flow and vascular resistance. Elements of hemodynamics. Endothelial physiology.
Regulation of cardio-vascular function: intrinsic and extrinsic control. Microcirculation and lymphatic system. Local and humoral control of blood flow by the tissues.
Baroreceptor reflex and other cardiovascular reflexes. Control of Arterial pressure: rapid, middle and long term regulation. Cardiac output, Venous return and their regulation. Control of cardiac output.
Coronary circulation and other specialized circulations (cerebral and fetal circulation). Physiological adaptations to specific conditions. Physiology of cardiovascular aging.
Physiology of the blood. Physical properties, viscosity. Sedimentation and centrifugation. Erythrocyte sedimentation rate. Haematocrit and viscosity.
PHYSIOLOGY OF RESPIRATION
The concept of breathing. External breathing. Lung as a gas exchanger. Airways and alveolar volume. Spirometry: lung volumes and capacities. Physical laws of gases.
Lung volumes, capacities and their measurement. The spirometer. Measurement and methods for measuring the residual functional capacity.
Ventilation. Definition and measurement. Total ventilation (volume/minute). Alveolar ventilation and its measurement. Lung dead space and measurement methods: Fowler method, Bohr method. Partial pressures of gases in the environment air and alveolar air. Alveolar air equations. Hyperventilation and hypoventilation. Distribution of ventilation.
Pulmonary mechanics. Mechanical thorax-lung coupling, origin of pleural pressure. Pneumothorax. Resting volumes of the lung, thorax and thorax-lung system. Volume-pressure relationship to release the chest, lung and chest-lung system. Compliance measurement method. Specific compliance. Elastic fibres. Role of surface tension. The surfactant. Stabilizing effect of the surfactant.
Resistance to flow in the respiratory act. Seat and factors that determine resistance to airway flow. Respiratory cycle analysis. Forced exhalation. Relationship between expiratory flow and volume. Airway compression and dynamics. Closing volume. Respiratory work. Respiratory loop.
Alveolus-capillary diffusion. Fick's law of alveolar diffusion. Equilibrium time of partial gas pressures across the alveolus-capillary membrane. Dissemination capacity. Pulmonary circulation.
Distribution of ventilation and perfusion. Ventilation / perfusion ratio. Inhomogeneity of the ventilation / perfusion ratio. CO2-O2 curve. Corrective mechanisms of the inhomogeneity of the ventilation / perfusion relationship.
Transport of oxygen in the blood. Blood capacity for oxygen. Hemoglobin. Saturation of hemoglobin for oxygen. Dissociation curve of hemoglobin for oxygen and effect on it of pCO2, pH and temperature. Bohr effect. Transport of CO2 into the blood. Blood capacity for CO2. Haldane effect.
Homeostasis of [H+] and its regulation. Blood buffer systems: bicarbonates, phosphates, hemoglobin, and proteins. Henderson-Hasselbalch equation. Davenport diagram. Metabolic or respiratory acidosis and alkalosis and their compensation. The concept of chemical bases overload.
Regulation of ventilation. Localization of respiratory centers. Types of respiratory neurons. Hering-Breuer reflection. Respiratory response to CO2, pH, O2. Peripheral and central chemoreceptors. Types of pathological breathing.
High altitude physiology, acclimatization, adaptation.
Hyperbaric physiology. Diving in apnea and with equipment. Effects of hyperbaric oxygen. Physiology of exercise.
Basic principles of renal physiology. Functional anatomy of the kidney. Renal vascular system. Composition and excretion of urine. Glomerular filtration. Glomerular filtration barrier. Composition of glomerular filtrate. Net ultrafiltration pressure. Ultrafiltration coefficient. Regulation of glomerular filtration.
Tubular processes: reabsorption and secretion. Net absorptive pressure. Paracellular and transcellular transport, active and passive mechanisms (Na+, amino acids, glucose, urea ). Tubular secretion of organic anions and cations.
Renal handling of filtered substances. Renal clearance. Inulin and creatinine, PAI, renal parameters.
Regulation of renal blood flow. Arterial pressure and renal autoregulation. Sympathetic regulation.
Regulation of extracellular osmolarity. Minimal urine volume. Urine concentration and dilution.
Countercurrent multiplier system and countercurrent exchange. Osmoreceptor control of vasopressin secretion. Renal control of water balance. Regulation of thirst and salt appetite.
Regulation of extracellular fluid volume (blood volume). Regulation of sodium balance. Integration of salt and water balance.
Hormonal control of kidney functions. Renin-angiotensin-aldosterone axis. Arginine vasopressin. Atrial natriuretic peptide. Parathormone. Renal regulation of acid-base balance. Excretion of acidic non-gases. Tubular secretion of H+. HCO3- handling. Renal responses to acidosis and alkalosis.
Renal regulation of K+, Ca2+, phosphate and magnesium homeostasis.
PHYSIOLOGY OF THE GASTROINTESTINAL SYSTEM
Intrinsic nervous system (enteric neurons and enteric glia cells) and extrinsic nervous control, endocrine and paracrine regulation (entero-endocrine cells). Intrinsic and extrinsic reflexes. Control of food intake. Electrical activity: interstitial cells of Cajal and slow waves, action potentials of smooth muscle cells.
Motility of the gastrointestinal system. Peristaltic contractions, segmental nonpropulsive contractions, tonic contraction of sphincters. Retroperistalsis. Vomiting reflex. Chewing. Swallowing: oral, pharyngeal and esophageal phases, primary and secondary peristalsis. Gastric motility: fundus relaxation, antro-duodenal pump, grinding, retropulsion, and gastric emptying. Entero-gastric reflexes. Motility of the small intestine: interdigestive (migrating motor complex), digestive (segmentation), mass peristalsis. Ileo-cecal sphincter. Motility of the large intestine: segmentation (haustration), mass peristalsis, gastrocolic reflex. Defecation reflex.
Secretions of the gastrointestinal system. Fluid balance in the gastrointestinal tract. Salivary secretion. Gastric secretion: mechanism and regulation of acid secretion (cephalic, gastric and intestinal phases), mucous gel layer and gastric diffusion barrier, secretion of pepsinogen, gastric lipase, and intrinsic factor. Pancreatic secretion: acinar and ductal cells, regulation of pancreatic fluid and digestive enzyme secretion. Physiology of the liver: bile secretion (bile salts and enterohepatic circulation, phospholipids, cholesterol, bile pigments, canalicular and ductal secretion), gallbladder filling and emptying, metabolic functions, detoxification and excretion of xenobiotics. Intestinal secretions.
Nutrient digestion and absorption. Carbohydrates, proteins, lipids. Intestinal absorption of vitamins, electrolytes and water, calcium and iron. Faecal composition.
Splanchnic circulation. Flow and pressure in intestine and portal system, metabolic, nervous and hormonal regulation.
Energy balance. Energy expenditure and energy dispersion as heat. Energy depots. Energy reserves. Measure of energy values of food constituents: calorimetric bomb, physical caloric value, physiological caloric value, absorption coefficient, net caloric value. Measure of energy expenditure: direct and indirect calorimetry (nutrients and respiratory thermochemistry). Oxygen consumption, CO2 production, respiratory quotient. Measure of protein consumption by ureic nitrogen. Calculation of glycidic and lipidic fractions.
Basal Metabolism. Measure by direct calorimetry based on oxygen consumption only. Normalization by body surface area. Variations of basal metabolism.
Total energy requirement. Contribution of basal metabolism, specific dynamic action of food, physical activity. Energy sources during physical exercise.
PHYSIOLOGY OF THE NERVOUS SYSTEM
Elements of functional neuroanatomy. The principles of functional differentiation and integration. Blood-brain barrier and cerebrospinal fluid.
Physiology of sensory systems
Psychophysiology. Sensory experience, sensation and perception. Adequate stimulation. Stimulus attributes: modality -sub-modality and quality - intensity, duration and localization. Neuronal coding of the stimulus attributes. Müller's specific energy law. Adaptation. Receptive field. Convergence and divergence. Lateral inhibition. Threshold and differential threshold concepts. Laws of psychophysics: Weber, Fechner and Stevens. Notes on the theory of sensory decision. Mechanoreoception, proprioception, thermoception and nociception. Receptors and their functional properties. Sensory acuity and its measure. Functional anatomy of the somatosensory system. Concept of dermatome and head area. System of dorsal columns - medial lemniscus. Antero-lateral system. Trigeminal system. The thalamus. Primary and secondary somatosensory cortical areas. Somatotopy. Columnar organization of the somatosensory cortex. Processing of tactile information.
Physiology of pain. Definition of pain. Characteristics and components of the pain sensation. Algometry. Nociception. Functional anatomy of nociception. Projected pain and reported pain. Causalgia and central pain. Pain inhibiting systems and descending systems. Elements of pain therapy.
Physiology of vision
Basic principles: dioptric system of the eye (outline of optical physics). Refractive defects. Spherical, chromatic aberration. Diffraction. Anatomy of the eye and annexes.
Adjustment of the dioptric system. Static and dynamic accommodation. Direct and consensual reflex and the corresponding nervous circuit. Intraocular pressure. Ophthalmoscope.
The retina. Histological description. Photoreceptors. Functional differences. Visual pigments. Phototransduction: Current in the dark. Interaction of light with the visual pigment. Early and treacherous receptor potential. Role of the cyclical GMP.
Light signal processing. Response of bipolar, horizontal and ganglion cells. Receptive fields. Ganglion cell classification. Visual field and visual pathways. Lateral geniculate body: functional anatomical subdivision and receptive fields. Primary visual cortex. Retinotopia. Receptive camps. Functional organization. Columns of ocular dominance and orientation. Blobs and inteblobs. Hierarchical systems in series and parallel systems for the perception of form, movement, stereopsis and color. Secondary visual areas. Visual agnosies. The vision of colors. Defects in color vision. Psychophysics of vision: adaptation to light and dark. Visual acuity. Simultaneous contrast. Temporal properties of retinal transmission, critical fusion frequency.
Physiology of hearing
Acoustic references: Sound, measures of sound intensity. The decibel. Psychophysics: psychophysical thresholds, audiogram and hair dryers. Transmission of the sound stimulus to the cochlear receptors. Transmission of sound vibration from the tympanic membrane to the oval window. Vibration of endocochlear fluids and of the basilar membrane. Sound transmission through bones. Mechanical-electrical transduction: Corti organ, colchlear receptors. Electrophysiology of the resting cochlea and of the cochlear responses to the acoustic stimulus. Electrical signals of the acoustic nerve. Functional anatomy and physiology of the acoustic pathways: Localization of the origin of the sound. Auditory cortex.
Physiology of taste and smell
Smell: transduction of the olfactory signals. Adaptation of olfactory receptors. Processing of sensory information in the olfactory bulb. Olfactory cortex. Taste: transduction of gustatory stimuli. Signal processing in the taste buds. Central pathways.
Introduction. Types of movement and their functions. General organization of the motor system and its hierarchical organization. Generation of motor commands: sensory-motor transformations, internal models, sources of inaccuracy, coordinate systems, motor schemes, feed-forward and feedback controls, motor adaptation.
Spinal cord. Myelomers, dermatomers and myomers. The common final pathway. Henneman's principle. Medial and lateral descending pathways. Neural circuits of spinal motor centers. Spinal reflexes. Components and adaptability of reflex responses. Myotatic reflex (by stretching). Interneuron Ia: mutual innervation and co-contraction. Physiology of neuromuscular spindles. Alpha-gamma coactivation. Static and dynamic fusimotor activity. Inverse myotatic reflex: Golgi tendon bodies and interneuron Ib. Recurrent Renshaw inhibitor circuit. Flexor reflex. H Reflex. Spinal cord section syndrome: spinal shock and recovery. Vestibular system. Mechanical-electrical transduction in the hair cells and recoding in the afferent fibers. Ampullary receptors: adequate stimulus, vestibular-ocular reflex, caloric stimulation, head impulse test (HIT). Macular receptors: adequate stimulus. Projections of the vestibular nuclei.
Posture and balance. Role of proprioceptive, vestibular and visual inputs. Postural balance. Postural responses.
Anticipatory postural adjustments. Role of sensory afferents. Postural reflexes of otolytic origin, from cervical proprioceptors and straightening reflexes. Lateral and medial descending pathways
Effects of brainstem lesions.
Locomotion. Step mechanics. Spinal locomotion. Spinal generators of the locomotor rhythm. Role of sensory afferents. Supraspinal locomotion control.
Eye movements. Extrinsic muscles and rotation axes. Micro-movements. Saccadic and slow pursuit movements: characteristics and control centers. Vestibular-ocular and optokinetic reflexes: reflex circuits and visuo-vestibular interaction. Vergence movements.
Cerebellum. Internal models and anticipatory signs. Physiology of the Purkinje cell, local circuits and microzones. The cerebellum as a variable controller: motor learning, reflex recalibration, long-term synaptic plasticity. Functional roles of: vestibolocerebellum, spinocerebellum, corticocerebellum. Motor effects of inactivation. Signs of cerebellar deficit.
Core of the base. Entry and exit routes. Direct and indirect route. Skeletal, oculomotor, prefrontal / decisional, limbic circuits. Striatum: organization of afferent and efferent pathways, neuronal types. Role of cholinergic and dopaminergic signals. Consequences of injury to the nuclei of the base. Notes on Parkinson's disease and Huntington's chorea.
Cortical control of movement. Properties of the short-descending pathways and consequences of their injury. Primary motor area: topographical representations, coding of muscle strength and direction of movement. Premotor areas and
their functional roles: supplementary motor (SMA and pre-SMA), rostral cingulate, dorsal premotor, ventral premotor (canonical, somatosensory, bimodal, mirror neurons), parietal association areas.
Vegetative nervous system
Autonomic nervous system. Functional organization. Sympathetic and parasympathetic system. Chemical mediators. Organization of vegetative reflexes of the spinal cord. Vagal tone and sympathetic tone. Vegetative functions of the brain stem. Vegetative reflex example: urination reflex.
Hypothalamus. Outlines of anatomy. Afferent and efferent systems. Hypothalamus and pituitary: concept of neurosecretion. Hypothalamus and cardiovascular system. Hypothalamus and behavior.
Physiology of emotions
Limbic system. Anatomo-functional organization, afferents and efferences. Emotion and limbic system. Theories of Papez and McLean. Role of the amygdala. Basic reasons. Thermoregulation, control of food intake. Control of the water supply.
Cortical electrical activity, wakefulness and sleep, consciousness.
The thalamus and the thalamocortical system. EEG, ECoG, MEG. Physical and biological basis. Registration methods. Evoked potentials. General concepts on neuroimaging techniques. Sleep and wake cycle. Circadian rhythms and sleep-wake rhythm. Sleep phenomenology, EEG and behavioral aspects. NREM sleep and REM sleep. Anatomical and neurophysiological foundations of sleep and wakefulness: anatomical structures and neuro-transmitters involved. Hypothesis on sleep functions. Consciousness and its physiological and pathological alterations.
Hemispheric language and dominance
Origins and development of language. Language lateralization. Brain areas involved in language. Theories. Aphasias.
Functional anatomy of the corpus callosum. Split-brain patients.