SECTION I: CELLULAR PHYSIOLOGY
Body Fluid Spaces
Lecture 1
Goals: After this lecture you should be able to
1. List the various fluid compartments of the body and their approximate relative sizes.
2. Describe several methods for measuring each compartment and explain why operational definitions are used.
3. State the major cations and anions of each compartment and their approximate concentrations.
Water Movement Across Biological Membranes
Lecture 2
Goals: After this lecture you should be able to
1. Define an osmole, osmotic pressure and how much pressure one osmole generates.
2. Explain the difference between total osmotic pressure and effective osmotic pressure.
3. Contrast hydrostatic pressure and osmotic (or effective osmotic) pressure.
4. Explain the fact that only the number, not the kind, of particles is important in calculating osmotic pressure.
5. Describe the effective osmotic pressure between the vascular compartment and the ISF and between the ISF and the ICF.
6. Define tonicity and describe how it is related to osmolarity.
7. Summarize the forces that result in movement of water across biological membranes.
8. Discuss the movements of fluid between the major compartments in conditions such as a) hemorrhage, b) sweating and c) starvation and other disturbances leading to hypoalbuminemia.
Origin of the Resting Membrane Potential
Lecture 3
Goals: After this lecture you should be able to
1. Describe the essential properties of ion channel proteins and their role in membrane electrical processes.
2. Describe the ionic basis of the resting membrane potential (RMP).
3. Explain the Nernst equation and how it can be used to calculate the RMP.
4. Explain the Goldman equation and how it can be used to calculate the RMP.
5. Describe how membrane capacitance is generated and what effect it has on the function of excitable membranes.
6. Describe the contribution of the Na+-K+ pump to the RMP.
Action Potentials in Nerve and Muscle
Lecture 4
Goals: After this lecture you should be able to
1. Describe the ionic bases of the depolarization, repolarization and afterpotential phases of the nerve action potential.
2. Describe the voltage-dependent sodium channel and how it contributes to the depolarization phase of the nerve action potential.
3. Describe the voltage-dependent potassium channel and how it contributes to the repolarization phase of the nerve action potential.
4. Explain the concept of driving force and how it is used to determine the direction of ion movements across a cell membrane during the action potential.
5. Explain the refractory period and its molecular basis.
6. Explain the role of Ca2+ and Cl- ions in the action potentials of cardiac and skeletal muscle.
7. Explain the concepts of threshold potential and regenerative depolarization in the context of action potential initiation.
Propagation of the Action Potential
Lecture 5
Goals: After this lecture you should be able to
1. Explain the mechanism of passive or electrotonic spread of membrane depolarization along a cell membrane.
2. Explain the mechanism of active propagation of the action potential.
3. Explain the mechanism of saltatory conduction of the action potential in myelinated neurons.
4. Explain how a Cl- channel mutation results in abnormal repolarization and repetitive firing of the action potential in Myotonia Congenita.
5. Explain how a Na+ channel mutation results in abnormal repolarization of the action potential, repetitive firing and paralysis in Hyperkalemic Periodic Paralysis.
6. Explain the effect of demyelination on conduction velocity and conduction efficiency in Multiple Schlerosis.
Section 2: MUSCLE PHYSIOLOGY
Structure-Function Relations in Striated Muscle
Lecture 1
Goals: After this lecture you should be able to
1. Draw a diagram of a skeletal muscle, showing the repeating subunits.
2. Explain the difference between a muscle fiber and a myofibril
3. Define and draw a sarcomere, showing the arrangement of the thick and thin filaments.
4. Identify the initial membrane stimulus that triggers contraction in striated muscle.
5 Define “isometric twitch” and “isometric tetanus”.
6. List the various routes by which Ca2+ enters the cell to initiate contraction, and the various mechanisms by which free Ca2+ concentration in the myoplasm is reduced back to the resting level to bring about relaxation.
7. Describe how the membrane stimulus is conveyed to the filament system and converted to mechanical force.
8. Explain the role of the sarcolemma, the transverse tubule system, the sarcoplasmic reticulum, and the regulatory proteins of the filament system in excitation- contraction coupling.
9. Describe the intermediate steps and the chemical second messengers involved in excitation-contraction coupling.
10. Describe the role of the sarcolemma, the transverse tubule system, and the sarcoplasmic reticulum in excitation-contraction coupling.
Muscle Performance
Lecture 2
Goals: After this lecture you should be able to
1. Describe the relationships that exist between muscle force and shortening velocity of contraction and relate these to structure.
2. Describe the effects of varying muscle (sarcomere) length and the force-velocity relationship.
3. List the major factors influencing the development of force at the level of the sarcomere.
4. List the major factors influencing the development of force at the level of the cell.
5. Describe how parallel or series assembly of sarcomeres into a muscle cell affects force and velocity.
6. Describe how parallel or series assembly of muscle cells (fibers) into a whole muscle affects force and velocity.
7. List the major factors influencing the development of maximum force in a whole muscle.
8. List the major factors influencing the development of a smooth, graded contractile force in a whole muscle.
Crossbridge Cycle to Organ Function
Lecture 3
Goals: After this lecture you should be able to
1. List the features common to all muscle systems and explain the role of Ca2+ and ATP in these systems.
2. Describe the mechanism by which troponin and tropomyosin transduce the [Ca2+]i signal to regulate contractility.
3. Describe how muscle Ca2+ sensitivity might be modulated.
4. Describe the structural considerations that lead to the concept of crossbridge cycling.
5. Describe the molecular structure of thick and thin filaments and integrate this with the biochemical data on isolated proteins to explain potential mechanisms for sliding filaments.
6. Give an order of magnitude for the number of crossbridge cycles per second and the consequent ATP use by muscle.
7. Discuss the energy sources and stores in skeletal muscle.
8. Describe how contractile ATP requirements are coordinated with metabolic energy sources.
9. Describe the structural and functional differences at the cellular level of the major skeletal muscle fiber types.
10. Describe the potential physiologic significance of isoform differences among the major muscle proteins
Smooth Muscle
Lecture 4
Goals: After this lecture you should be able to
1. Compare and contrast the major structural and functional differences between smooth and skeletal muscle.
2. Describe the differences in excitation-contraction coupling between striated muscle and smooth muscle, and how these differ from that for skeletal muscle.
3. Compare and contrast the major modes of activation of striated and smooth muscle at the contractile filament level.
4. Explain how the Ca2+ -sensitivity of smooth muscle may be altered.
Section 3: CARDIAC PHYSIOLOGY
Overview of Cardiac Function and Electro-Mechanical Coupling
Lecture 1a
Goals: After this lecture you should be able to
1. Describe the functional anatomy of the heart—its inlets, outlets and valves as well as the directional flow of blood through the heart.
2. Describe the general organization of the autonomic nervous system and explain how stimulation of its two branches, the sympathetic and parasympathetic, influences cardiac performance.
3. List the four requirements for effective cardiac pumping.
4. Describe the general principles of the cardiac pump cycle and the parameters determining cardiac output.
5. Describe the generation of electrical impulses and the pathway of action potential propagation in the heart.
6. Identify the distribution of sympathetic and parasympathetic nerves in the heart and predict the physiologic effects of activation of these nerves.
7. Describe the major events involved in electro-mechanical coupling in the heart, including the roles of the T-tubular system, sarcoplasmic reticulum, Ca2+ movements and the cross-bridge cycle.
Cardiac Output 1: Preload, Afterload and Contractility
Lecture 1b
Goals: After this lecture you should be able to
1. Describe the major determinants of cardiac output and how the autonomic nervous system affects heart rate.
2. Describe the complex fashion in which stroke volume is controlled.
3. Describe the fundamental principles of cardiac muscle mechanics—isometric contractions and the length-tension relationship; isotonic contractions, preload and afterload.
4. Describe the relationship between force and velocity of shortening in cardiac muscle.
5. Define and state the major factors affecting contractility of cardiac muscle.
6. Describe how contractility is assessed and define ejection fraction.
7. Describe the effect of heart rate on contractility and understand the mechanisms underlying the staircase effect and postextrasystolic potentiation.
Cardiac Output 2: Pressure-Volume Relationships & the Cardiac Function Curve
Lecture 2
Goals: After this lecture you should be able to
1. Relate the variables length, tension, shortening, preload, afterload and contractility to filling volume, pressure, ejection volume, EDV, arterial pressure and contractility of the intact heart.
2. Describe how length-tension relationships relate to volume vs. pressure through the Law of LaPlace.
3. Describe how the Law of LaPlace predicts the pathologic consequences of an enlarged heart operating at an increased radius.
4. Describe the cardiac pump cycle in terms of left ventricular pressure-volume loops and predict the effects of changes in preload, afterload and contractility.
5. Define and calculate stroke work and minute work (power) and understand their major determinants.
6. Describe the interplay between changes in preload, afterload and contractility in the beat-to-beat regulation of cardiac output.
7. Describe the difference between homeometric and heterometric regulation of cardiac output.
8. Describe how cardiac function curves are generated, why they represent preload-dependent events and how alterations in contractility and afterload affect the curves.
9. Describe the changes in stroke volume and heart rate (and their interplay) that occur with increases in cardiac output during strenuous exercise.
Venous Return and Estimates of Cardiac Function
Lecture 3
Goals: After this lecture you should be able to
1. Define venous return and understand why it must equal cardiac output in the steady state.
2. List the factors that control venous return and describe the relationship between venous return and central venous pressure as plotted in the normal venous return curve.
3. Define peripheral venous pressure and state the factors that determine it.
4. Describe the shifts in the venous return curve that occur with changes in blood volume and venous tone.
5. Construct a normal venous return curve and a cardiac output curve on the same graph and describe the significance of the point of intersection of the two curves.
6. Predict how normal venous return, cardiac output and central venous pressure are altered when changes occur in cardiac sympathetic tone, peripheral venous sympathetic tone or circulating blood volume.
7. Describe how to measure cardiac output using either the Fick Principle, the indicator-dilution technique or central venous pressure. Define and calculate cardiac index.
8. Describe how to estimate cardiac contractility using imaging techniques, the ejection fraction or pressure - volume relationships of the intact ventricle.
9. Calculate and discuss the difference between total, forward and regurgitant stroke volumes and how the regurgitant fraction varies with valvular disease.
The Integrated Cardiac Cycle
Lecture 4
Goals: After this lecture you should be able to
1. Correlate electrical events in the heart with mechanical events occurring during the cardiac cycle.
2. Describe the major distinct events of the cardiac cycle occurring between each valve opening and closing.
3. Describe the pressure and volume changes in the atria, ventricles and the aorta during each phase of the cardiac cycle.
4. List normal values for cardiac chamber pressures during the cardiac cycle and those for ventricular end-diastolic volume, end-systolic volume, stroke volume, diastolic pressure, systolic pressure and pulse pressure.
5. Describe the similarities and differences between the mechanical events in the left and right heart pumps.
6. Describe the mechanical events associated with the major heart sounds.
Coronary Blood Flow and Oxygen Utilization
Lecture 5
Goals: After this lecture you should be able to
1. Define and calculate oxygen extraction of the myocardium and understand why oxygen delivery to the heart is “flow limited”.
2. Describe the functional anatomy of the coronary circulation and the role of coronary collaterals.
3. Describe the phasic changes in coronary blood flow during the cardiac cycle and why they occur.
4. Describe systolic compression and its relative importance to blood flow in the endocardial and epicardial regions of the heart wall.
5. List the major determinants of coronary blood flow and its regulation.
6. Describe the role of oxygen demand in determining local blood flow and describe the “adenosine hypothesis.”
7. State the factors involved in determining normal myocardial oxygen balance and the metabolic substrates utilized by the heart under resting conditions and during exercise.
8. Explain the role of the autonomic nervous system in regulating coronary blood flow and define coronary autoregulation of blood flow.
Section 4: PHYSIOLOGY OF THE CIRCULATION
Hemodynamics and the Arterial System
Lectures 1 and 2
Goals: After these lectures you should be able to
1. Describe the factors that regulate blood flow and pressure in the arterial system.
2. Describe the concepts of transmural pressure and vascular compliance in the regulation of blood flow and arterial pressure.
3. Describe the relationship between blood flow velocity and cross-sectional area in the vascular tree.
4. State Poiseuille’s Equation and Laplace’s Law and describe laminar and turbulent flow patterns..
5. Discuss the concept of total peripheral resistance and how changes in resistance affect pressure and flow.
The Microcirculation and Transcapillary Exchange
Lectures 3 and 4
Goals: After these lectures you should be able to
1. Describe how different vessel and cell types control blood flow and transcapillary exchange in the microcirculation.
2. Describe how flow through the microcirculation is controlled by intrinsic and extrinsic mechanisms.
3. Describe how transcapillary exchange is controlled by diffusion, ultrafiltration, and pinocytosis.
4. Describe the role of the lymphatic system in regulating of transcapillary filtration.
The Venous System and Special Circulations
Lecture 5
Goals: After this lecture you should be able to
1. Describe the role of the venous system as a high capacitance storage reservoir.
2. Describe the effect of gravity on venous return to the heart.
3. Discuss the relationship between venous return and cardiac output.
4. Discuss the concepts of “peripheral” and “central” venous pressure and the role of these pressures in determining venous return.
5. Describe the mechanical (e.g. hydrostatic pressure vs. pulmonary arterial pressure) and chemical factors (e.g. oxygen tension) that regulate flow in the pulmonary circulation.
6. Describe the autoregulation of cerebral blood flow and the metabolic factors that influence blood flow through the whole brain and discrete brain regions.
7. Describe the role of cutaneous blood flow in the regulation of temperature.
Regulation of the Systemic Circulation
Lecture 6
Goals: After this lecture you should be able to
1. Discuss the general organization of the cardiovascular control system.
2. Discuss the regulation of blood pressure by the arterial baroreceptor reflex.
3. Discuss the role of arterial chemoreceptors in the regulation of arterial pressure.
4. Discuss the role of reflexes that are activated by increased intracardiac or pulmonary pressure.
5. Discuss the effect of circulating hormones on the control of arterial pressure.
6. Discuss the role of the endothelial cell in regulating vascular smooth muscle contractility.
7. Discuss the importance of body fluid volume regulation in long-term control of arterial pressure.
Section 5: HEMOSTASIS
Platelet-Vessel Wall Interactions
Lecture 1
Goals: After this lecture you should be able to
1. Define hemostasis and describe conceptually where the hemostatic mechanism is operative in relation to the conditions of thrombosis and hemorrhage.
2. Explain why the hemostatic mechanism is a “potential” one and describe the adequate stimuli that are necessary to elicit the response.
3. Illustrate how the hemostatic mechanism may be stimulated by abnormal processes leading to thrombosis.
4. Explain why an inability of the mechanism to respond to a stimulus such as vascular injury may result in fatal hemorrhaging.
5. List the basic components of the normal hemostatic response to vessel injury.
6. Describe the mechanisms by which platelets interact with an injured vessel wall to form a temporary hemostatic plug.
7. Delineate those factors that necessitate the transformation of the temporary hemostatic plug to a definitive mass of fibrin.
Mechanisms of Blood Coagulation
Lecture 2
Goals: After this lecture you should be able to
1. Describe the production of coagulation factors and the role of vitamin K in coagulation factor synthesis.
2. Describe the major enzymatic pathways of blood coagulation and the mechanisms by which they are initiated.
3. Contrast the kinetics of thrombin evolution via the extrinsic pathway versus the intrinsic pathway.
4. Explain the necessity of having both pathways of coagulation operative for normal coagulation.
5. List the diverse effects of thrombin and explain its pivotal role in the overall hemostatic response to vessel injury.
Regulation of Coagulation
