9797194 - THE CELL: FUNCTIONS AND REGULATIONS
Modulo Cellular physiology

By the end of the course, students are expected to:

·        Understand the biophysical laws involved in body function regulation. 

·        Understand basic neurophysiology, with particular reference to cellular excitability mechanisms and neurotransmission.

THE CELL AS AN INTEGRATED SYSTEM

·         Dynamic balance, cell functions, the cell as a thermodynamic system, energy and entropy, the cell as a chemical system.

·         Gas and solute exchanges through cell membranes (Fick's law, passive diffusion, facilitated diffusion, controlled diffusion, primary and secondary active transport).

·         Homeostasis, steady state, regulation of cellular functions.

GAS LAWS AND THEIR APPLICATIONS

·         Ideal gas law, Boyle's law, Charles and Gay-Lussac’s law, second law of Gay-Lussac, Avogadro's law, Dalton's law, Graham's Law, Henry's Law, Laplace’s law. Applications in physiology and pathophysiology (physiological polycythemia, high-altitude sickness, decompression sickness).

FLUID COMPARTEMENTS AND HOMEOSTASIS

·         Human body fluid compartments: intracellular and extracellular compartments, compartments volumes and methods for their measurements. Sources and removal of body fluids. Water and salts balance.

·         Exchanges of water and electrolytes through biological membranes. Concentration and electrochemical gradients. Saline, isotonic and iso-osmotic solutions, and their use. Osmotic pressure: definition, units of measurements, plasma values. Van't Hoff’s law, Gibbs-Donnan equilibrium. Hydrostatic pressure. Colloid osmotic and oncotic pressure: plasmas value and fluctuations. Consequences of oncotic pressure modifications. Starling's law and capillary exchanges. Pathophysiology: edema.

PRINCIPLES OF HEMODYNAMICS AND HEMORHEOLOGY 

·         Systemic circulation: generalities. Blood volume and velocity in different areas of the vascular system. Morphological and physiological characteristics of vessels: arteries, capillaries and veins.

·         Blood flow: physical factors affecting blood flow. Bernoulli’s principle. Pressure, flow and resistance: Hagen-Poiseuille Law. Blood viscosity: relationship between viscosity and hematocrit. Turbulent blood flow. Laplace's law applied to vessels.

·         Vascular tone: nervous, hormonal and humoral control.

ION CHANNELS AND MEMBRANE POTENTIAL 

·         Cell excitability: cell membrane polarization, depolarization and hyperpolarization.  Ion channels: voltage-gated ion channels for sodium, potassium, calcium, chloride (characteristics, functions, main agonist and antagonists), electrophysiological techniques (patch clamp), Pathophysiology: channelopathies.

·         Electric potentials: membrane potential, electrochemical potential, Nernst equation, Goldman equation. Genesis and characteristics of an action potential. All-or-none law. Refractory period. Membrane repolarization. Graded potentials.

·         Excitability conduction along cell membranes. Propagation velocity. Saltatory or continuous conduction, myelin sheath.

SYNAPTIC TRANSMISSION 

·         Excitable cells communication. Electric and chemical synapses. Synaptic types. 

·         Neurotransmitters and neuropeptides: synthesis, transport, release and secretion, neurotransmitter release cycle, vesicle cycle (trafficking). 

·         Neuromuscular junction. Endplate potential, miniature potential, quantal neurotransmitter release. 

·         Synaptic integration and transmission in CNS (EPSP, IPSP, spatial and temporal summation). 

·         Ionotropic and metabotropic receptors.

·         Synaptic plasticity, Hebbian theory, long-term and short-term plasticity (long-term potentiation e long-term depression).

NEUROTRANSMITTERS AND RECEPTORS

·         Acetylcholine, nicotinic receptors, muscarinic receptors, cholinergic synapses, main agonists and antagonists, pathophysiology: Myasthenia gravis.

·         Glutamate glutamine cycle, NMDA, AMPA and Kainate receptors, metabotropic receptors, involvement in synaptic plasticity (LTP), main agonists and antagonists, Pathophysiology: glutamate excitotoxicity, notes on related diseases (Alzheimer’s disease, glutamate hypothesis of schizophrenia). 

·         GABA, Ionotropic and metabotropic receptors, Notes on benzodiazepine, barbiturate and alcohol mechanism of action. Pathophysiology: Anxiety, Epilepsy.  

·         Catecholamine and their receptors, Role in SNA, Notes on stress and catecholamine.

·         Dopamine and its receptors. Pathophysiology: Addiction, Parkinson’s disease, Schizophrenia. 

·         Serotonin and its receptors, Drugs acting on serotonin receptors. Pathophysiology: mood disorders.

·         Endocannabinoids and opioids, notes on drug abuse (cocaine, amphetamine, heroine, hallucinogens, etc.) 

·         Nitric oxide pathway and retrograde transmission.

MUSCLE CONTRACTION 

·         Skeletal muscles: structure, myofibrils, sarcomere and mechanisms of contraction, Sliding filament theory of muscle contraction, Neuromuscular junction, Excitation-Contraction Coupling, single muscle twitch and tetanus, isometric and isotonic contraction, length-tension curve, force-velocity curve, muscle energetics, oxygen consumption, muscle work, performance, and fatigue. Muscle fibers. Skeletal muscle innervation. Electromyogram.

·         Smooth muscle: generalities, unitary and multiunit muscles, structure, contraction mechanisms, contraction regulation (arteriolar tone), biomechanics. 

·         Cardiac muscle: generalities, structure, contraction mechanisms, contraction regulation, biomechanics.

NERVOUS SYSTEM: GENERALITIES 

·         Neuron: morphologic, functional, biochemical and trophic unit of the nervous system.

·         Kandel ER et al. Principles of Neural Science, The McGraw-Hill Companies, Inc.

·         Hall, J. E. Guyton and hall textbook of medical physiology. W B Saunders.

The assessment of acquired knowledge is carried out through a written exam consisting of 60 true/false questions covering 15 topics from the curriculum. Each correct answer is awarded 1 point, each incorrect answer deducts 1 point, and unanswered questions receive zero points. The minimum passing score for the assessment is 27 out of 60. This score is then converted on a scale of thirty, up to a maximum of 30/30 cum laude (with honors). 

1. They are mostly found in the intracellular compartment:

·         sodium (True/False)

·         chloride (True/False)

·         bicarbonate (True/False)

·         proteins (True/False)

2. The following mechanisms are involved in long-term potentiation:

·         Phosphorylation of AMPA receptors (True/False)

·         Activation of CaMKII (True/False)

·         Activation of the CREB transcription factor (True/False)