1.Introduction to the course (1 hour)

2. The Cardiovascular System (18 hours)
2.1 Introduction to the cardiovascular system: anatomy and general functions.
2.2 The heart (schematic drawing): pacemaker and contractile tissue; contractile myocardial cells and intercalary discs (schematic drawing); morpho-functional differences between myocardiocytes and skeletal muscle fibers; excitation-contraction coupling: differences between mechanical coupling and Ca2 +-induced Ca2 +-release (CICR).
2.3 Conduction, potentials and electro-cardiogram: ion equilibrium potentials; the conduction system (schematic drawing of its various components); the action potential of pacemaker cells (graph); the action potential of contractile cells (graph); the electrocardiogram (graph); autonomic control of the heart rate.
2.4 The cardiac cycle: explained with the 5 phases; explained with the pressure-volume curve of the left ventricle (graph); systolic and cardiac output (formula); Wiggers diagram; heart sounds; the Frank-Starling law (graphic) and the importance of venous return; reflex control of myocardial contractility: inotropic and lusitropic effect; factors affecting cardiac output.
2.5 General characteristics of smooth muscle cells; unitary and multi-unit smooth muscle; the neuro-effector junction; organization of thick and thin myofilaments; molecular mechanisms of contraction and relaxation: role of calmodulin and myosin light chain phosphorylation; the different mechanisms of activation of smooth muscle contraction; the myogenic response.
2.6 The large and small circulation: physical laws underlying the flow of liquids: hydrostatic pressure and hydraulic pressure; law of Hagen-Poiseuille; structure of blood vessels: arteries, arterioles, capillaries and veins; continuous or fenestrated capillaries; the importance of metarterioles; role of dovetail valves in veins; main differences between arteries and veins and their role in helping the heart to pump blood; the elastic return of the arteries: the windkessel effect; vascular compliance or capacitance; role of the skeletal muscle pump and the ventilatory (or respiratory or thoracic) pump.
2.7 Blood pressure: mean arterial pressure (MAP) and factors that influence it; blood pressure and how it drops along the circulation; measurement of blood pressure (concept of systolic and diastolic pressure); pressure (or sphygmic) waves; blood distribution to the tissues: sympathetic control of the vessels diameter; local control of blood flow: active and reactive hyperemia; blood volume and blood pressure; factors affecting the regulation of blood pressure and baroceptive reflex (schematic drawing of its functioning); orthostatic hypotension.
2.8 The blood: plasma composition; plasma proteins; serum; corpuscular elements of the blood: red blood cells, white blood cells and platelets; role of red blood cells and hemoglobin in oxygen transport; concept of hematocrit; hematopoiesis; hemostasis and coagulation; clot removal.

3. The Kidney and the Hydro-Electrolytic Balance (14 hours).
3.1 Introduction to the urinary system: urinary tract and kidney; main functions of the kidneys: cortex and medulla; the nephron (schematic drawing of its different parts): tubular and vascular elements; cortical and juxta-medullary nephrons; structure of the renal or Malpighi corpuscle (schematic drawing); juxta-glomerular apparatus (schematic drawing).
3.2 The four fundamental processes of nephron (filtration, reabsorption, secretion, excretion); the filtration barrier; concept of filtration fraction and filtration pressure; self-regulation of glomerular filtration rate (graph): myogenic response and tubulo-glomerular feedback; fundamental principles underlying reabsorption (eg: sodium, glucose, urea, water); transport saturation concept; glucose reabsorption; renal clearance; reabsorption in the peritubular capillaries; urination reflex.
3.3 Water and electrolyte balance: distribution of liquids in the body: intracellular, extracellular and plasma compartments; cardiovascular and renal responses to changes in blood volume and blood pressure; water balance and the role of the kidney in its regulation; vasopressin or antidiuretic hormone: signals that induce its secretion; countercurrent exchange in the medulla of the kidney (schematic drawing of its functioning); the role of urea in increasing the concentration gradient of the medulla; sodium and potassium balance: role of aldosterone; via renin-angiotensin-aldosterone (RAAS); the antagonists of the RAAS pathway: natriuretic peptides; behavioral mechanisms in the hydro-electrolyte balance: thirst, appetite for salt, avoidance of heat.
3.4 Acid-base balance: blood buffer systems, ventilation, renal regulation of H + and HCO3-; the kidney buffer systems; function of intercalated cells of type A and B of the collecting duct; metabolic and respiratory acidosis and alkalosis.

4. The Gastrointestinal System, Metabolism and Energy Balance (12 hours)
4.1 Introduction to the gastrointestinal (GI) system: anatomy and general functions; the wall of the intestinal tract: mucosa, submucosa, muscular tunica, and serous; similarity and differences of the wall between the various sections of the GI tract.
4.2 The 4 fundamental functions of the GI system: digestion, secretion, absorption and motility; different types of motility: migrating motor complex, peristalsis and segmental contractions; the regulation of GI function: the enteric nervous system (ENS or small brain); short and long reflexes.
4.2 Beginning of digestion: cephalic, oral, and gastric phase; chemical and mechanical gastric digestion; gastric epithelium and its secretions: acidic, enzymatic, and paracrine; balance between digestion and protection; regulation of the gastric phase of digestion.
4.3 Intestinal phase of digestion: villi and crypts; liver, pancreas and gallbladder; hepatic portal system; pancreatic and intestinal enzymatic secretion; secretion of bicarbonate; secretion of bile; digestion and absorption of fats, carbohydrates and proteins; digestion and absorption of iron, calcium, vitamins, and nucleic acids; regulation of the intestinal phase of digestion; the large intestine (or colon): its different sections; the colon wall; motility of the large intestine; digestion and absorption in the colon; reflex of defecation.
4.4 Metabolism and energy balance: the hypothalamic centers of eating behavior; glucostatic and lipostatic theory for the regulation of food intake; signals of appetite and satiety; body metabolism: assimilative and post-assimilative phase; distribution of glycogen and lipid reserves in the body. Hormonal control of metabolism: endocrine pancreas and stimuli that influence insulin and glucagon secretion; transport of glucose in the tissues; energy balance: energy input and energy output; factors affecting basal resting metabolic rate.
Body temperature regulation: the cost of thermogenesis; metabolic efficiency in the transfer of energy to glycogen and fat deposits; heat balance, a balance between heat gain and loss; heat production: thermogenesis with thrill and without thrill; heat gain: radiation and conduction; heat loss: conduction, radiation, convection and evaporation; control of body temperature by the hypothalamus: the center of thermoregulation; peripheral and central temperature receptors; spino-thalamic sensory pathways; the thermoregulatory reflex: mechanisms of vasodilation, vasoconstriction, and sweating.

5. The Integrative Seminars (5 hours).

The Human Physiology course will also include a cycle of 5 seminars, which will be held within normal teaching hours; dates will be scheduled at least one week in advance. Listed below the titles of seminars 2020-21:

a. Environmental Heat Stroke: can we develop a cure?
b. Store-Operated Ca2+ entry in muscle: where?
c. STIM1 and Orai1 entrapped by ageing in tubular aggregates.
d. Mitochondrial position and muscle efficiency.
e. The Telethon Mission: find a cure for rare genetic diseases.