Department of Physiology

Syllabus

Medical Physiology I and II

Trinity School of Medicine

St. Vincent

2010

Faculty

Stephen C. Wood, Ph.D., Course Coordinator

Phone: 505-507-5624 (cell)

Email: scwood@salud.unm.edu

Curriculum Vitae

Visiting faculty (use IE to view this page, not Firefox)

Course Description

The two semester course in medical physiology will include lectures, clinical correlations, laboratories, and case studies. Semester 1 covers general and cell physiology, cardiovascular, renal, and respiratory physiology. Semester 2 covers endocrinology, reproduction, gastrointestinal, and integrative physiology. Introduction to neurophysiology may be taught in either Semester 1 or 2.

Resources

Textbook: Costanzo, Physiology, 4th edition (Saunders). The 3rd edition may also be used.

Internet resources:

Costanzo:     http://www.studentconsult.com/default.cfm

Department: http://www.trinityphysiology.org



Exams and Grading

Your grade for each semester will be calculated as follows:

Unifying exam 1          = 35%

Unifying exam 2          = 35%

Final exam                 = 25%

Other (quizzes, PBL) = 5%

The final exam for the second semester course will the NBME shelf exam for physiology

Learning Objectives for Medical Physiology

Competencies expected of medical students for the USMLE Step 1 exam are published by the American Physiological Society (APS) in association with chairs of physiology departments in the USA. http://www.the-aps.org/education/MedPhysObj/medcor.htm.
These are competencies expected of you in fifth semester, when you take the USMLE Step 1 exam. Objectives not covered in the first two semesters will be covered in other classes; e.g., biochemistry and anatomy, and in semester 3 and 4 classes; e.g., neuroscience and pathology.

Each physiology lecture will include a Power Point handout and the learning objectives for that topic. All exam questions will be based on the learning objectives provided for each lecture.The PowerPoint files for each lecture are available online at:http://www.trinityphysiology.org. Click on the faculty name to go to the folder with PowerPoint files.

Objectives below are examples from the objectives of the APS:

Semester 1 Topics (click on topic to go to objectives for that topic)

Cell

Muscle

Neurophysiology

Pulmonary Physiology

Cardiovascular Physiology

Renal Physiology

Semester 2 Topics (click on topic to go to objectives for that topic)

        Gastrointestinal Physiology

Endocrinology

Reproductive Physiology

        Integrative Physiology

Semester 1 Learning Objectives

Cellular Physiology

Body Fluids

1. Given the body weight and percent body fat, estimate the a) total body water, b) lean body mass, c) extracellular fluid volume, d) intracellular fluid volume, e) blood volume, and f) plasma volume. Identify normal extracellular fluid (plasma) osmolarity and concentrations of Na⁺, K⁺, Cl^-, HCO₃^-, proteins, creatinine, and urea, and contrast these values with those for intracellular fluids.

2. Given the composition and osmolality of a fluid, identify it as hypertonic, isotonic, or hypotonic. Predict the change in transcellular fluid exchange that would be caused by placing a red blood cell in solutions with varying tonicities.

Biological Membranes, Solutes and Solutions, and Transport across Cell Membranes

1. Describe the composition of a cell membrane. Diagram its cross section, and explain how the distribution of phospholipids and proteins influences the membrane permeability of ions, hydrophilic and hydrophobic compounds.

2. Contrast the osmotic pressure generated across a cell membrane by a solution of particles that freely cross the membrane with that of a solution with the same osmolality, but particles that cannot cross the cell membrane.

3. Differentiate between the terms osmole, osmolarity, osmolality and tonicity. List the typical value and normal range for plasma osmolality.

4. Write the equation for Fick�s Law of diffusion, draw a graph of this equation and explain how changes in the concentration gradient, surface area, time, and distance will influence the diffusional movement of a compound.

5. Explain how the resting membrane potential is generated.

6. Differentiate the following terms based on the source of energy driving the process and the molecular pathway for: diffusion, facilitated diffusion, secondary active transport, and primary active transport.

7. Describe how energy from ATP hydrolysis is used to transport ions such as Na⁺, K⁺, Ca²⁺, and H⁺ against their electrochemical differences (e.g., via the Na⁺ pump, sarcoplasmic reticulum Ca²⁺ pump, and gastric H⁺pump).

8. Explain how energy from the Na⁺ and K⁺ electrochemical gradients across the plasma membrane can be used to drive the net �uphill� (against a gradient) movement of other solutes (e.g., Na⁺/glucose co-transport; Na⁺/Ca²⁺ exchange or counter-transport). Apply this principle to predict possible therapies for secretory diarrhea.

9. Describe the role of water channels (aquaporins) in facilitating the movement of water across biological membranes.

Excitable Cells

1. Know the properties of voltage-gated Na⁺, K⁺, and Ca²⁺ channels, and understand that voltage influences their gating, activation, and inactivation.

2. Understand how the activity of voltage-gated Na⁺, K⁺, and Ca²⁺ channels generates an action potential and the roles of those channels in each phase (depolarization, overshoot, repolarization, hyperpolarization) of the action potential.

3. Contrast the mechanisms by which an action potential is propagated along both nonmyelinated and myelinated axons. Predict the consequence on action potential propagation in the early and late stages of demyelinating diseases, such as multiple sclerosis.

Transcapillary Transport

1. Predict the permeability of cardiovascular capillaries to small ions/crystalloids (e.g., NaCl) and proteins (albumin) based on the capillary reflection coefficient.

2. Based on the Starling hypothesis, explain how permeability, hydrostatic pressure and oncotic pressure influence transcapillary exchange of fluid.

Muscle

Skeletal Muscle Structure and Mechanism of Contraction

1. Draw and label a skeletal muscle at all anatomical levels, from the whole muscle to the molecular components of the sarcomere. At the sarcomere level, include at two different stages of myofilament overlap.

2. Draw a myosin molecule and label the subunits (heavy chains, light chains) and describe the function of the subunits.

3. Diagram the structure of the thick and thin myofilaments and label the constituent proteins.

4. Describe the relationship of the myosin-thick filament bare zone to the shape of the active length:force relationship.

5. Diagram the chemical and mechanical steps in the cross-bridge cycle, and explain how the cross-bridge cycle results in shortening of the muscle.

Control of Skeletal Muscle Contraction: Excitation-Contraction Coupling

6. List the steps in excitation-contraction coupling in skeletal muscle, and describe the roles of the sarcolemma, transverse tubules, sarcoplasmic reticulum, thin filaments, and calcium ions.

7. Describe the roles of ATP in skeletal muscle contraction and relaxation.

8. Draw the structure of the neuromuscular junction.

9. List in sequence the steps involved in neuromuscular transmission in skeletal muscle and point out the location of each step on a diagram of the neuromuscular junction.

10. Distinguish between an endplate potential and an action potential in skeletal muscle.

11. List the possible sites for blocking neuromuscular transmission in skeletal muscle and provide an example of an agent that could cause blockage at each site.

Mechanics and Energetics of Skeletal Muscle Contraction

12. Explain the relationship of preload, afterload and total load in the time course of an isotonic contraction.

13. Distinguish between an isometric and isotonic contraction.

14. Distinguish between a twitch and a tetanus in skeletal muscle and explain why a twitch is smaller in amplitude than a tetanus.

15. Draw the length versus force diagram for muscle and label the three lines that represent passive (resting), active, and total force. Describe the molecular origin of these forces.

16. Explain the interaction of the length:force and the force:velocity relationships.

17. Draw force versus velocity relationships for two skeletal muscles of equal maximum force generating capacity but of different maximum velocities of shortening.

18. Using a diagram, relate the power output of skeletal muscle to its force versus velocity relationship.

19 Describe the influence of skeletal muscle tendons on contractile function.

20. List the energy sources of muscle contraction and rank the sources with respect to their relative speed and capacity to supply ATP for contraction.

21. Define muscular fatigue. List some intracellular factors that can cause fatigue.

22. Construct a table of structural, enzymatic, and functional features of fast-glycolytic and slow-oxidative fiber types from skeletal muscle.

23. Describe the role of the myosin cross bridges acting in parallel to determine active force and the rate of cross bridge recycling to determine muscle speed of shortening and rate of ATP utilization during contraction.

24. Discuss the functional consequences of the parallel and series arrangement of myofibrils in a skeletal muscle.

25. Describe how the arrangement of a skeletal muscle to the skeleton can influence mechanical performance of the muscle.

26. Define a motor unit and describe the order of recruitment of motor units during skeletal muscle contraction of varying strengths.

Smooth Muscle

27. Describe the differences in actomyosin regulation of, respectively, smooth and skeletal muscle and indicate the structural similarities in their respective contractile units.

28. Compare and contrast the length versus force relationships in skeletal and smooth muscle. Describe the functional implications of the differences observed.

29. Compare and contrast the force versus velocity relationships in skeletal and smooth muscle. Describe the primary cause for the observed differences in velocity of shortening.

30. Explain why smooth muscles can develop and maintain force with a much lower rate of ATP hydrolysis than skeletal muscle.

31. Distinguish between muscle relaxation from the contracted state and the phenomenon of stress relaxation and give examples of each process.

32. Diagram the intracellular pathways that control contraction and relaxation in smooth muscle.

33. Describe the distinguishing characteristics of multi-unit and unitary smooth muscles.

Cardiac Muscle

34. Describe the structure of cardiac muscle cells, comparing and contrasting it with that of smooth and skeletal muscle cells. Describe the physiological consequences of the low-resistance pathways between cardiac muscle cells.

35. Diagram the relationship between the action potential and a twitch in cardiac muscle and explain why this prevents a tetanic contraction.

36. Diagram the steps in the excitation-contraction coupling mechanism in cardiac muscle and compare with skeletal muscle.

37. Diagram the length versus force curve for cardiac muscle and skeletal muscle, showing the active and passive relationships, and indicate the range over which each muscle type performs its physiological function.

38. Define contractility in cardiac muscle. On the length versus force diagram, indicate the pathway for an isotonic contraction of cardiac muscle and show how an increase in contractility changes the relationship between afterload and amount of shortening.

39. List some inotropic interventions that could change cardiac contractility.

Neurophysiology

1.   Neurophysiology Overview

a.   Know basic vocabulary of the nervous system

b.   Identify the organizing principles of the nervous system (neuron, functional groups, hierarchy)

c.   Become familiar with a few methods of how the nervous system is studied

2.   Motor Systems

a.   List the pathway of movement from motor cortex to muscle

b.   Become familiar with a few diseases affecting this system

c.   Describe the properties of motor units and muscle spindles

d.   Describe 3 types of spinal reflexes

3.   Sensory Systems

a.   Understand common features of the sensory systems

b.   Become familiar with the basic organization of the somatosensory system

c.   Understand the topography and physiology of signaling for the somatosensory system

4.   Higher Cortical Systems

a.   List the lobes of the cerebrum and their major functions

b.   Define the different types of memory

c.   Describe the cellular basis for learning and memory

5.    Cranial Nerves and Reflexes Lab

a.   Name each cranial nerve, its function, and demonstrate how to test it

b.    Understand the mechanics and physiology of the deep tendon reflex

6.   Write the Nernst equation, and explain the effects of altering either the intracellular or extracellular Na⁺, K⁺, Cl^-, or Ca²⁺ concentration on the equilibrium potential for that ion.

7.   Describe the normal distribution of Na⁺, K⁺, Ca²⁺, and Cl^- across the cell membrane, and using the chord conductance equation, explain how the relative permeabilities to these ions create a resting membrane potential.

8.   Describe ionic basis of an action potential.

Pulmonary Physiology

Pulmonary Mechanics

1. Diagram how pleural pressure, alveolar pressure, airflow, and lung volume change during a normal quiet breathing cycle. Identify on the figure the onset of inspiration, cessation of inspiration, and cessation of expiration. Describe how differences in pressure between the atmosphere and alveoli cause air to move in and out of the lungs.

2. Draw a normal pulmonary pressure-volume (compliance) curve (starting from residual volume to total lung capacity and back to residual volume), labeling the inflation and deflation limbs. Explain the cause and significance of the hysteresis in the curves.

3. Define compliance and identify two common clinical conditions in which lung compliance is higher or lower than normal.

4. Draw the pressure-volume (compliance) curves for the lungs, chest wall, and respiratory system on the same set of axes. Show and explain the significance of the resting positions for each of these three structures.

5. Identify the forces that generate the negative intrapleural pressure when the lung is at functional residual capacity, and predict the direction that the lung and chest wall will move if air is introduced into the pleural cavity (pneumothorax).

6. Draw a normal spirogram, labeling the four lung volumes and four capacities. List the volumes that comprise each of the four capacities. Identify which volume and capacities cannot be measured by spirometry.

7. Define the factors that determine total lung capacity, functional residual capacity, and residual volume. Describe the mechanisms responsible for the changes in those volumes that occur in patients with emphysema and pulmonary fibrosis.

8. Define surface tension and describe how it applies to lung mechanics, including the effects of alveolar size and the role of surfactants. Define atelectasis and the role of surfactants in preventing it.

9. Describe the principal components of pulmonary surfactant and explain the roles of each.

10. Describe the effects of airway diameter and turbulent flow on airway resistance.

11. Describe how airway resistance alters dynamic lung compliance.

12. Draw a spirogram resulting from a maximal expiratory effort. Label the forced vital capacity (FVC), timed forced expiratory volumes (FEVs), and the maximal expiratory flow rate between 25-75% of FVC (FEF25-75%).

13. Draw a normal maximal effort flow-volume curve, labeling the effort-dependent and -independent regions. Use the concept of dynamic compression of airways to explain why each point in the effort-independent region of the curve represents a maximal flow rate that is uniquely dependent on lung volume. Describe how and why the shape of the flow-volume curve is shifted in chronic obstructive lung disease (COPD).

14. Differentiate between the two broad categories of restrictive and obstructive lung disease, including the spirometric abnormalities associated with each category.

15. Describe the regional differences in alveolar ventilation in healthy and diseased lungs and explain the basis for these differences.

Alveolar ventilation

16. Define partial pressure and fractional concentration as they apply to gases in air. List the normal fractional concentrations and sea level partial pressures for O₂, CO₂, and N₂.

17. List the normal airway, alveolar, arterial, and mixed venous PO₂ and PCO₂ values. List the normal arterial and mixed venous values for O₂ saturation, [HCO₃^-], and pH.

18. Define and contrast the following terms: anatomic dead space, physiologic dead space, wasted (dead space) ventilation, total minute ventilation and alveolar minute ventilation.

19. Describe the concept by which physiological dead space can be measured.

20. Define and contrast the relationships between alveolar ventilation and the arterial PCO₂ and PO₂.

21. Describe in quantitative terms the effect of ventilation on PCO₂ according to the alveolar ventilation equation.

22. Be able to estimate the alveolar oxygen partial pressure (PAO₂) using the simplified form of the alveolar gas equation. Be able to use the equation to calculate the amount of supplemental O₂ required to overcome a reduction in PAO₂ caused by hypoventilation or high altitude.

23. Define the following terms: hypoventilation, hyperventilation, hypercapnea, eupnea, hypopnea, and hyperpnea.

Pulmonary Circulation

24. Contrast the systemic and pulmonary circulations with respect to pressures, resistance to blood flow, and response to hypoxia.

25. Describe the regional differences in pulmonary blood flow in an upright person. Define zones I, II, and III in the lung, with respect to pulmonary vascular pressure and alveolar pressure.

26. Describe how pulmonary vascular resistance changes with alterations in cardiac output or pulmonary arterial pressure. Explain in terms of distention and recruitment of pulmonary vessels. Identify the zones in which these two mechanisms apply.

27. Describe how pulmonary vascular resistance changes with lung volume. Explain in terms of alterations in alveolar and extra-alveolar blood vessels.

28. Describe the consequence of hypoxic pulmonary vasoconstriction on the distribution of pulmonary blood flow.

29. Describe the effects of inspired nitric oxide on pulmonary vascular resistance and hypoxic vasoconstriction.

30. Explain the development of pulmonary edema by a) increased hydrostatic pressure, b) increased permeability, c) impaired lymphatic outflow or increased central venous pressure, and d) hemodilution (e.g., with saline volume resuscitation).

31. Describe the major functions of the bronchial circulation.

Pulmonary Gas Exchange

32. Name the factors that affect diffusive transport of a gas between alveolar gas and pulmonary capillary blood.

33. Describe the kinetics of oxygen transfer from alveolus to capillary and the concept of capillary reserve time (i.e., the portion of the erythrocyte transit time in which no further diffusion of oxygen occurs).

34. Define oxygen diffusing capacity, and describe the rationale and technique for the use of carbon monoxide to determine diffusing capacity.

35. Describe how the ventilation/perfusion (V/Q) ratio of an alveolar-capillary lung unit determines the PO₂ and PCO₂ of the blood emerging from that lung unit.

36. Identify the average V/Q ratio in a normal lung. Explain how V/Q is affected by the vertical distribution of ventilation and perfusion in the healthy lung.

37. Describe the normal relative differences from the apex to the base of the lung in alveolar and arterial PO₂, PCO₂, pH, and oxygen and carbon dioxide exchange.

38. Predict how the presence of abnormally low and high V/Q ratios in a person's lungs will affect arterial PO₂ and PCO₂.

39. Describe two causes of abnormal V/Q distribution.

40. Define right-to-left shunts, anatomic and physiological shunts, and physiologic dead space (wasted ventilation). Describe the consequences of each for pulmonary gas exchange.

41. Describe the airway and vascular control mechanisms that help maintain a normal ventilation/perfusion ratio. Name two compensatory reflexes for V/Q inequality.

42. Be able to calculate the alveolar to arterial PO₂ difference, (A-a)DO₂. Describe the normal value for (A-a) DO₂ and the significance of an elevated (A-a) DO₂.

43. Describe five causes of hypoxemia and identify those that result in a lower PO₂and those that result in a lower O₂ content.

Oxygen and Carbon Dioxide Transport

44. Define oxygen partial pressure (tension), oxygen content, and percent hemoglobin saturation as they pertain to blood.

45. Draw an oxyhemoglobin dissociation curve (hemoglobin oxygen equilibrium curve) showing the relationships between oxygen partial pressure, hemoglobin saturation, and blood oxygen content. On the same axes, draw the relationship between PO₂ and dissolved plasma O₂ content (Henry�s Law). Compare the relative amounts of O₂ carried bound to hemoglobin with that carried in the dissolved form.

46. Describe how the shape of the oxyhemoglobin dissociation curve influences the uptake and delivery of oxygen.

47. Define P50.

48. Show how the oxyhemoglobin dissociation curve is affected by changes in blood temperature, pH, PCO₂, and 2,3-DPG, and describe a situation where such changes have important physiological consequences.

49. Describe how anemia and carbon monoxide poisoning affect the shape of the oxyhemoglobin dissociation curve, PaO₂, and SaO₂.

50. List the forms in which carbon dioxide is carried in the blood. Identify the percentage of total CO₂ transported as each form.

51. Describe the importance of the chloride shift in the transport of CO₂ by the blood.

52. Identify the enzyme that is essential to normal carbon dioxide transport by the blood and its location.

53. Draw the carbon dioxide dissociation curves for oxy- and deoxyhemoglobin. Describe the interplay between CO₂ and O₂ binding on hemoglobin that causes the Haldane effect.

54. Explain why the total gas pressure of the venous blood is subatmospheric and why this situation is accentuated when breathing 100% O₂. Explain how breathing 100% O₂ can result in further arterial O₂ desaturation in hypoxemic patients who develop mucous plugging of their airways (absorption atelectasis).

55. Define respiratory acidosis and alkalosis and give clinical examples of each.

56. Describe the mechanism and function of respiratory acid base compensations.

Respiratory Control

57. Identify the regions in the central nervous system that play important roles in the generation and control of cyclic breathing.

58. Give three examples of reflexes involving pulmonary receptors that influence breathing frequency and tidal volume. Describe the receptors and neural pathways involved.

59. List the anatomical locations of chemoreceptors sensitive to changes in arterial PO₂, PCO₂, and pH that participate in the control of ventilation. Identify the relative importance of each in sensing alterations in blood gases.

60. Describe how changes in arterial PO₂ and PCO₂ alter alveolar ventilation, including the synergistic effects when PO₂ and PCO₂ both change.

61. Describe the respiratory drive in a COPD patient, and predict the change in respiratory drive when oxygen is given to a COPD patient.

62. Describe the mechanisms for the shift in alveolar ventilation that occur immediately upon ascent to high altitude, after remaining at altitude for two weeks, and immediately upon return to sea level.

63. Describe the physiological basis of shallow water blackout during a breath-hold dive.

64. Describe the significance of the feedforward control of ventilation (central command) during exercise, and the effects of exercise on arterial and mixed venous PCO₂, PO₂, and pH.

Age Effects and Non-respiratory Lung Functions

65. Describe the effect of aging on lung volumes, lung and chest wall compliance, blood gases, and respiratory control.

66. Identify the mechanism by which particles are cleared from the airways.

67. Describe mechanisms for clearance of vasoactive substances from the blood during passage through the lung. Identify a substance that is almost completely cleared and one that is not cleared to any significant extent.

Cardiovascular Physiology

Electrophysiology of the Heart

1. Contrast the duration of the action potential and the refractory period in a cardiac muscle, a skeletal muscle, and a nerve. Sketch the temporal relationship between an action potential in a cardiac muscle cell and the resulting contraction (twitch) of that cell.

2. State the steps in excitation‑contraction coupling in cardiac muscle. Outline the sequence of events that occurs between the initiation of an action potential in a cardiac muscle cell and the resulting contraction and then relaxation of that cell. Provide specific details about the special role of Ca²⁺ in the control of contraction and relaxation of cardiac muscle.

3. Compare cardiac and skeletal muscle with respect to: cell size, electrical connections between cells, and arrangement of myofilaments. Based on ion permeability and electrical resistance describe role of gap junctions in creating a functional syncytium.

4. Identify the role of extracellular calcium in cardiac muscle contraction. Identify other sources of calcium that mediate excitation‑contraction coupling, and describe how intracellular calcium concentration modulates the strength of cardiac muscle contraction.

5. Describe the role of Starling�s Law of the Heart in keeping the output of the left and right ventricles equal.

6. Describe the difference in the way changes in preload and changes in contractility influence ventricular force development. Compare the energetic consequences of these two separate mechanisms of force modulation.

7. Describe how ionic currents contribute to the four phases of the cardiac action potential. Use this information to explain differences in shapes of the action potentials of different cardiac cells.

8. Explain what accounts for the long duration of the cardiac action potential and the resultant long refractory period. What is the advantage of the long plateau of the cardiac action potential and the long refractory period?

9. Beginning in the SA node, diagram the normal sequence of cardiac activation (depolarization) and the role played by specialized cells. Predict the consequence of a failure to conduct the impulse through any of these areas.

10. Explain why the AV node is the only normal electrical pathway between the atria and the ventricles, and explain the functional significance of the slow conduction through the AV node. Describe factors that influence conduction velocity through the AV node.

11. Explain the ionic mechanism of pacemaker automaticity and rhythmicity, and identify cardiac cells that have pacemaker potential and their spontaneous rate. Identify neural and humoral factors that influence their rate.

12. Contrast the sympathetic and parasympathetic nervous system influence on heart rate and cardiac excitation in general. Identify which arm of the autonomic nervous system is dominant at rest and during exercise. Discuss ionic mechanisms of these effects on both working myocardium and pacemaker cells.

Cardiac Function

1. Draw and describe the length tension relationship in a single cardiac cell. Correlate the cellular characteristics of length, tension, and velocity of shortening with the intact ventricle characteristics of end diastolic volume, pressure, and dP/dt.

2. Define preload and explain why ventricular end-diastolic pressure, atrial pressure and venous pressure all provide estimates of ventricular preload. Explain why ventricular end-diastolic pressure provides the most reliable estimate.

3. Define afterload and explain how arterial pressure influences afterload. Describe a condition when arterial pressure does not provide a good estimate of afterload.

4. Define contractility and explain why dP/dt is a useful index of contractility. Explain how the calcium transient differs between cardiac and skeletal muscle and how this influences contractility.

5. Define the difference between cardiac performance and cardiac contractility. Describe the impact of changes in preload, afterload, and contractility in determining cardiac performance.

6. Explain how changes in sympathetic activity alter ventricular work, cardiac metabolism, oxygen consumption and cardiac output.

7. Write the formulation of the Law of LaPlace. Describe how it applies to ventricular function in the normal and volume overloaded (failing) ventricle.

8. Draw a ventricular pressure volume loop and on it label the phases and events of the cardiac cycle (ECG, valve movement).

9. Differentiate between stroke volume and stroke work. Identify stroke volume and stroke work from a pressure-volume loop.

10. Define ejection fraction and be able to calculate it from end diastolic volume, end systolic volume, and/or stroke volume. Predict the change in ejection fraction that would result from a change in a) preload, b) afterload, and c) contractility.

11. Draw the change in pressure volume loops that would result from changes in a) afterload, b) preload, or c) contractility, for one cycle and the new steady state that is reached after 20 or more cycles.

Cardiac Cycle

1. Understand the basic functional anatomy of the atrioventricular and semilunar valves, and explain how they operate.

2. Draw, in correct temporal relationship, the pressure, volume, heart sound, and ECG changes in the cardiac cycle. Identify the intervals of isovolumic contraction, rapid ejection, reduced ejection, isovolumic relaxation, rapid ventricle filling, reduced ventricular filling and atrial contraction.

3. Know the various phases of ventricular systole and ventricular diastole. Contrast the relationship between pressure and flow into and out of the left and right ventricles during each phase of the cardiac cycle.

4. Understand how and why left sided and right sided events differ in their timing.

Physiology of Cardiac Defects (Heart Sounds)

1. Know the factors that contribute to the formation of turbulent flow.

2. Describe the timing and causes of the four heart sounds.

3. Describe the expected auscultation sounds that define mitral stenosis, mitral insufficiency, aortic stenosis, and aortic insufficiency. Explain how these pathologic changes would affect cardiac mechanics and blood pressure.

The Electrocardiogram

1. Define the term dipole. Describe characteristics that define a vector. Describe how dipoles generated by the heart produce the waveforms of the ECG.

2. Describe the electrode conventions used by clinicians to standardize ECG measurements. Know the electrode placements and polarities for the 12 leads of a 12 lead electrocardiogram and the standard values for pen amplitude calibration and paper speed.

3. Name the parts of a typical bipolar (Lead II) ECG tracing and explain the relationship between each of the waves, intervals, and segments in relation to the electrical state of the heart.

4. Define mean electrical vector (axis) of the heart and give the normal range. Determine the mean electrical axis from knowledge of the magnitude of the QRS complex in the standard limb leads.

5. Describe the alteration in conduction responsible for most common arrhythmias: i.e., tachycardia, bradycardia, A V block, Wolff-Parkinson-White (WPW) syndrome, bundle branch block, flutter, and fibrillation.

6. Describe electrocardiographic changes associated respectively with myocardial ischemia, injury, and death. Define injury current and describe how it is alters the S T segment of the ECG.

Cardiac Output and Venous Return

1. Understand the principles underlying cardiac output measurements using the Fick, dye dilution, and thermodilution methods.

2. Know how cardiac function (output) curves are generated and how factors which change contractility in the heart can alter the shape of cardiac function curves.

3. Understand the concept of �mean systemic pressure,� its normal value, and how various factors can alter its value.

4. Define venous return and describe how various interventions would change the resistance to venous return.

5. Construct a vascular function curve. Predict how changes in total peripheral resistance, blood volume, and venous compliance influence this curve.

6. Explain why the intersection point of the cardiac function and vascular function curves represents the steady-state cardiac output and central venous pressure under the conditions represented in the graph.

7. Use the intersection point of the cardiac function curve and vascular function curve to predict how interventions such as hemorrhage, heart failure, autonomic stimulation, and exercise will affect cardiac output and right atrial pressure.

Fluid Dynamics

8. Discuss the normal balance of red blood cell synthesis and destruction, including how imbalances in each lead to anemia or polycythemia.

9. Differentiate between flow and velocity in terms of units and concept.

10. Understand the relationship between pressure, flow, and resistance in the vasculature and be able to calculate for one variable if the other two are known. Apply this relationship to the arteries, arterioles, capillaries, venules, and veins. Explain how blood flow to any organ is altered by changes in resistance to that organ.

11. Explain how Poiseuille�s Law influences resistance to flow. Use it to calculate changes in resistance in a rigid tube (blood vessel). Explain the deviations from Poiseuille's law predictions that occur in distensible blood vessels.

12. Understand the relationship between flow, velocity, and cross-sectional area and the influence vascular compliance has on these variables.

13. Define resistance and conductance. Understand the effects of adding resistance in series vs. in parallel on total resistance and flow. Apply this information to solving problems characterized by a) resistances in series and b) resistances in parallel.

14. List the factors that shift laminar flow to turbulent flow. Describe the relationship between velocity, viscosity, and audible events, such as murmurs and bruits.

15. Understand the principles of flow through collapsible tubes, the Starling resistor, and what pressure gradient determines flow for different relative values of inflow, surrounding, and outflow pressures.

Arterial Pressure and the Circulation

1.Compare and contrast the pulmonary and systemic circulations.

2. Describe blood pressure measurement with a catheter and transducer and explain the components of blood pressure waveform. Contrast that with the indirect estimation of blood pressure with a sphygmomanometer.

3. Given systolic and diastolic blood pressures, calculate the pulse pressure and the mean arterial pressure.

4. Describe how arterial systolic, diastolic, mean, and pulse pressure are affected by changes in a) stroke volume, b) heart rate, c) arterial compliance, and d) total peripheral resistance.

5. Contrast pressures and oxygen saturations in the arteries, arterioles, capillaries, venules, and veins of both the systemic and pulmonary circulations.

6. Contrast velocity of blood flow, cross-sectional area, and volume saturations in the arteries, arterioles, capillaries, venules, and veins of both the systemic and pulmonary circulations.

7. Identify the cell membrane receptors and second messenger systems mediating the contraction of vascular smooth muscle by norepinephrine, angiotensin II, and vasopressin.

8. Identify the cell membrane receptors and second messenger systems mediating the relaxation of vascular smooth muscle by nitric oxide, bradykinin, prostaglandins, and histamine.

The Microcirculation and Lymphatics

1. Explain how water and solutes traverse the capillary wall. Use Fick�s equation for diffusion to identify the factors that will affect the diffusion mediated delivery of nutrients from the capillaries to the tissues. Define and give examples of diffusion-limited and flow-limited exchange.

2. Define the Starling equation and discuss how each component influences fluid movement across the capillary wall.

3. Describe how smooth muscle contractile mechanisms differ from the contractile mechanisms of skeletal and cardiac muscle.

4. Describe the involvement of G protein-coupled receptors and signal transduction pathways in the regulation of smooth muscle contraction.

5. Predict how altering pressure or resistance in pre- and post-capillary regions alters capillary pressure and the consequence of this change on transmural fluid movement.

6. Using the components of the Starling equation, explain why fluid does not usually accumulate in the interstitium of the lungs.

7. Describe how histamine alters the permeability of the post capillary venules, and how the loss of albumin into the interstitial space promotes localized edema.

8. Describe the role of the lymphatics in tissue fluid balance and explain why edema does not normally develop as interstitial pressure increases.

9. Explain how edema develops in response to: a) venous obstruction, b) lymphatic obstruction, c) increased capillary permeability, d) heart failure, e) tissue injury or allergic reaction, and f) malnutrition.

Regulation of Arterial Pressure

1. Explain the sequence of events in the baroreflex that occur after an acute increase or decrease in arterial blood pressure. Include receptor response, afferent nerve activity, CNS integration, efferent nerve activity to the SA node, ventricles, arterioles, venules, and hypothalamus.

2. Explain the sequence of events mediated by cardiopulmonary (volume) receptors that occur after an acute increase or decrease in arterial blood pressure. Include receptor response, afferent nerve activity, CNS integration, efferent nerve activity to the heart, kidney, hypothalamus, and vasculature.

3. Explain the sequence of events mediated by cardiopulmonary (volume) receptors that occur after an acute increase or decrease in central venous pressure. Include receptor response, afferent nerve activity, CNS integration, efferent nerve activity to the heart, kidney, hypothalamus, and vasculature.

4. Contrast the sympathetic and parasympathetic nervous system control of heart rate, contractility, total peripheral resistance, and venous capacitance. Predict the cardiovascular consequence of altering sympathetic nerve activity and parasympathetic nerve activity.

5. Contrast the relative contribution of short- and long-term mechanisms in blood pressure and blood volume regulation.

6. Outline the cardiovascular reflexes initiated by decreases in blood O₂ and increases in blood CO₂.

7. Describe the release, cardiovascular target organs, and mechanisms of cardiovascular effects for angiotensin, atrial natriuretic factor, bradykinin, and nitric oxide.

Local Control of Blood Flow

1. Describe mechanisms of autoregulation of blood flow to the brain. Distinguish between short-term and long-term autoregulatory responses and the mechanisms responsible for each.

2. Describe how the theory of metabolic regulation of blood flow accounts for active hyperemia and reactive hyperemia.

3. Identify the role of PO₂ , PCO₂ , pH, adenosine, and K⁺ in the metabolic control of blood flow to specific tissues including lungs.

4. Diagram the synthetic pathway for nitric oxide (EDRF, endothelial derived relaxing factor), including substrate and the interplay between endothelium and vascular smooth muscle.

5. Describe the role of angiogenesis in providing a long term match of tissue blood flow and metabolic need.

Fetal and Neonatal Circulation

1. Describe the progressive changes in maternal blood volume, cardiac output, and peripheral resistance during pregnancy and at delivery.

2. Contrast the blood flow pattern in the fetus with that of a normal neonate, including the source of oxygenated blood.

3. Describe the function in utero of the fetal ductus venosus, foramen ovale, and ductus arteriosus. Explain the mechanisms causing closure of these structures at birth.

4. Discuss the relative differences in oxygen saturation and pressure for blood in the major blood vessels and cardiac chambers of the fetus. Explain how these values change at birth.

5. Explain the unfavorable consequences to the neonate if either the ductus arteriosis or the foramen ovale fails to close.

Hemostasis and Injury, Hemorrhage, Shock

1. Describe the direct cardiovascular consequences of the loss of 30% of the circulating blood volume on cardiac output, central venous pressure, and arterial pressure. Describe the compensatory mechanisms activated by these changes.

2. Explain three positive feedback mechanisms activated during severe hemorrhage that may lead to circulatory collapse and death.

3. Contrast the change in plasma electrolytes, hematocrit, proteins, and colloid osmotic pressure following resuscitation from hemorrhage using a) water, b) 0.9% NaCl, c) plasma, and d) whole blood.

Coronary and Skeletal Muscle Circulations

1. Describe the phasic flow of blood to the ventricular myocardium through an entire cardiac cycle. Contrast this cyclic variation in myocardial flow a) in the walls of the right and left ventricles and b) in the subendocardium and subepicardium of the left ventricle. Identify the area of the ventricle most susceptible to ischemic damage and why the risk is increased at high heart rates.

2. Explain how arterio-venous O₂ difference and oxygen extraction in the heart is unique when compared with other body organs.

3. Explain the mechanism whereby coronary blood flow is coupled to myocardial workload, and identify stimuli that cause increases in coronary blood flow to occur.

4. Explain how sympathetic stimulation alters heart rate, contractility, and coronary vascular resistance, as well as both directly and indirectly to change coronary blood flow. Identify the relative importance of the direct and indirect SNS effects in determining coronary blood flow during exercise.

5. Describe what is meant by coronary vascular reserve and the role of collateral blood vessels. Discuss physiological and pathological events that decrease coronary vascular reserve.

6. Contrast the neural and local control of skeletal muscle blood flow at rest and during exercise.

7. Contrast the effect of phasic and sustained skeletal muscle contraction on compression of blood vessels and on central venous pressure.

Cerebral, Splanchnic and Cutaneous Circulation

1. Contrast the local and neural control of cerebral blood flow. Discuss the relative important of O₂, CO_2,and pH in regulating cerebral blood flow.

2. Describe the structural components of the blood brain barrier and how this barrier impedes the movement of gases, proteins, and lipids from the blood to neurons. Identify the differences in cerebrospinal fluid and plasma relative to protein concentration, and describe the function of cerebrospinal fluid.

3. Contrast the mechanisms of the two major types of stroke, hemorrhagic and occlusive stroke.

4. Contrast the local and neural control of the splanchnic circulation. Describe the role of the hepatic portal system and the hepatic artery in providing flow and oxygen to the liver.

5. Describe the blood pressure in the hepatic portal vein, hepatic sinusoids, and the vena cava. Given an increase in central venous pressure, predict how hepatic microcirculatory fluid exchange will be altered, including the development of ascites.

6. Describe how the GI circulation is adapted for secretion and absorption. Explain the enterohepatic circulation.

7. Contrast local and neural control of cutaneous blood flow.

8. Discuss the unique characteristics of skin blood flow that are adaptive for body temperature regulation.

Exercise

1. Describe the cardiovascular consequences of exercise on peripheral resistance, cardiac output, A V oxygen difference, and arterial pressure.

2. Describe the redistribution of cardiac output during exercise to the CNS, coronary, splanchnic, cutaneous, and skeletal muscle vascular beds during sustained exercise (distance running). Explain the relative importance of neural and local control in each vascular bed.

3. Discuss four adaptations to physical training on the cardiovascular system. Explain the mechanisms underlying each.

4. Contrast the effects of static vs. dynamic exercise on blood pressure.

Semester 2 Learning Objectives

Renal Physiology

Renal Clearance

1. Explain the clearance principle. Use the clearance equation and an appropriate compound to estimate the glomerular filtration rate, renal plasma flow, and renal blood flow.

2. Given the plasma and urine concentrations and the urine flow rate, calculate the filtered load, tubular transport, excretion rate, and clearance of inulin, creatinine, para‑amino hippuric acid (PAH), glucose, and penicillin. Predict how changes in filtration, reabsorption, and secretion will affect renal excretion of each compound.

3. For each of the compounds listed in objective 2, graph the urine excretion of a compound against the plasma concentration. Using this graph, identify the tubular load, tubular transport maximum (T_max), and splay for each substance.

Glomerular Filtration Rate and Renal Hemodynamics

1. Define renal blood flow, renal plasma flow, glomerular filtration rate, and filtration fraction and list typical values.

2. Define the filtration coefficient at the glomerular capillary, describe the membrane properties that contribute to it, and explain its role in determining GFR.

3. Given the capillary and Bowman�s capsule hydrostatic and oncotic pressures, calculate the net filtration force at the glomerular capillaries. Predict the changes in glomerular filtration caused by increases or decreases in any of those pressures.

4. Describe the relative resistances of the afferent and efferent arterioles and the effects on renal blood flow and GFR of selective changes in each.

5. Describe the myogenic and tubuloglomerular feedback mechanisms that mediate the autoregulation of renal plasma flow and glomerular filtration rate.

6. Predict the change in renal blood flow and glomerular filtration rate caused by an increase in renal sympathetic nerve activity.

7. Predict the change in renal blood flow and glomerular filtration caused by: a) increased synthesis of angiotensin II, b) increased release of atrial natriuretic peptide, c) increased prostaglandin formation, and d) increased nitric oxide formation.

8. Predict the change in renal blood flow and GFR caused by urinary tract obstruction, hypoalbuminemia, and diabetic nephropathy.

9. Compare blood flow to, and oxygen consumption by, the kidneys with that of skeletal muscle and cardiac muscle.

Transport Properties of Nephron Segments

1. Describe the contribution of the major nephron segments to the reabsorption of the filtered load of solute and water.

2. Describe the cellular mechanisms for the transport of Na⁺, Cl^-, K⁺, HCO₃^-, Ca²⁺, phosphate, organic solutes (e.g., glucose, amino acids, and urea), and water by the major tubular segments.

3. Describe the function of the following renal transporters and their predominant localization along the tubules with regard to nephron segment and apical versus basolateral membranes

a. Transport ATPases (Na⁺/K⁺‑ATPase, H⁺/K⁺‑ATPase, H⁺‑ATPase, and Ca²⁺‑ATPase)

b. Ion and water channels (K⁺, ENaC, Cl^, Ca²⁺, aquaporins)

c. Coupled transporters (Na⁺‑glucose, Na⁺/H⁺‑antiporter, Na⁺‑K⁺‑2Cl^‑‑symporter, Na⁺‑phosphate symporter, Na⁺‑Cl^‑‑symporter, Na⁺‑HCO₃^‑‑symporter, Cl^‑/HCO₃^‑‑antiporter)

4. Describe the nephron sites and molecular mechanisms of action of the following classes of diuretics (osmotic, carbonic anhydrase inhibitors, loop, thiazide, K⁺‑sparing).

5. Describe clinical syndromes related to defects in specific renal transporters (e.g., Bartter�s, Gittelman�s, Liddle�s, etc.).

6. Describe the effects of reductions in GFR on plasma creatinine concentrations and plot the relationship

Urine Concentration and Dilution



1. Identify the two most powerful stimuli that cause ADH release, and describe the negative feedback control mechanisms for each.

2. Describe the role of the ascending limb of the loop of Henle in producing a high renal interstitial fluid osmolality. Beginning with the loop of Henle, contrast the tubular fluid and interstitial fluid osmolality changes that allow either a dilute or a concentrated urine to be produced and excreted.

3. Identify the tubular section and cellular mechanism by which ADH increases permeability to water and urea. Describe the role of these changes on the ability of the kidney to produce either a dilute or a concentrated urine.

4. Distinguish between central and nephrogenic diabetes insipidus based on plasma ADH levels and the response to an injection of ADH.

Na⁺ Balance and Regulation of Extracellular Fluid Volume

1. Describe the receptors involved in the monitoring of ECF volume (e.g., high-pressure baroreceptors and low-pressure cardiopulmonary stretch receptors), and diagram the neural reflex regulation of renal Na⁺ and water excretion.

2. Diagram the formation and generation of angiotensin II, beginning with renin. Identify four factors that can promote renin release.

3. Describe the regulation of Na⁺ reabsorption along the nephron, including the effects of sympathetic nerves, angiotensin II, aldosterone, and atrial natriuretic peptide

4. Describe the regulation of proximal tubule reabsorption that underlies the phenomenon of glomerulotubular balance.

5. Describe the role of the renin‑angiotensin‑aldosterone system in the regulation of systemic arterial blood pressure in volume-replete and volume-depleted states and in secondary forms of hypertension.

6. Use the indicator dilution principle to measure plasma volume, blood volume, extracellular fluid volume, and total body water, and identify compounds used to measure each volume.

7. Predict the changes in extracellular volume, extracellular osmolality, intracellular volume, and intracellular osmolality caused by infusion of three liters of 0.9% NaCl, lactated Ringer�s solution, 0.45% NaCl, and 7.5% NaCl.

K⁺ Balance

1. Identify the normal range of dietary K⁺ intake and major routes of K⁺ loss from the body. Define the role of extracellular K⁺ in maintaining normal nerve and muscle function.

2. Describe K⁺ distribution within the body, extrarenal K⁺ homeostasis, and the role insulin, epinephrine, and aldosterone play in the movement of K⁺ between intracellular and extracellular pools. Describe the K⁺ shift caused by acidosis.

3. Describe the factors that regulate K⁺ secretion in the collecting duct (i.e., aldosterone, plasma K⁺) and distinguish these from factors that alter K⁺ secretion at this site (i.e., luminal fluid flow rate, acid‑base disturbances, anion delivery).

Ca²⁺ and Phosphate Balance

1. Identify the normal range of dietary Ca²⁺ and phosphate intake, major storage pools of Ca and phosphate, and major routes of Ca²⁺and phosphate loss from the body. Describe the regulation of plasma Ca²⁺ by calcitonin and phosphate by parathyroid hormone.

2. Describe the role of the kidney in the production of 1,25‑dihydroxy vitamin D (calcitriol).

Acid-Base Balance

1. Identify the normal range of pH values, and the upper and lower limits compatible with life. Describe the role of buffers in maintaining pH, including the roles of the lungs and kidneys.

2. Describe the respiratory and renal regulation of the CO₂/HCO₃^- buffer system, which allows a buffer with a pK_a of 6.1 to be physiologically important in the maintenance of the normal plasma pH of 7.4.

3. Distinguish between CO₂‑derived (volatile acid) and nonvolatile acid, the relative amounts produced each day through dietary intake and cellular metabolism, and the normal routes of loss from the body.

4. Calculate the filtered load of HCO₃^‑, and identify the major sites of reabsorption (and secretion) along the nephron, emphasizing the importance of H⁺ secretory mechanisms in this process. Describe the cellular mechanisms responsible for net transepithelial movement of HCO₃^‑.

5. Describe net acid excretion by the kidneys, titratable acid, the importance of urinary buffers, and the production and excretion of ammonium. Distinguish between the reclamation of filtered bicarbonate and the formation of new bicarbonate.

6. Given a sudden increase or decrease in pH, identify the magnitude and the time course of the compensations that act to minimize change in pH of the body fluids, including a) buffers, b) respiratory adjustments, and c) renal adjustments.

7. From blood values, identify simple and mixed metabolic and respiratory acid‑base disturbances. Distinguish between increased and normal anion gap metabolic acidosis, chloride-sensitive and -resistant metabolic alkalosis, and acute and chronic respiratory disturbances.

8. Describe processes that lead to acid‑base disturbances and list common causes

9. Describe the effects of carbonic anhydrase inhibitors on acid‑base balance and the reabsorption of HCO₃^‑ by the nephron.

Integrative and Pathophysiological Aspects of Renal Physiology

1. Describe the role of the renin-angiotensin-aldosterone systems in the regulation of sodium balance and arterial pressure with emphasis on the actions of angiotensin II on various target organs and tissues.

2. Describe pressure natriuresis and the mechanisms mediating and modulating this process.

Gastrointestinal Physiology

Functions and Regulation of GI Tract

1. Describe the overall role of the gastrointestinal system with respect to the whole body balance of water, electrolytes, carbohydrates, fats, and proteins. Include the processes of digestion, absorption, metabolic production, metabolic consumption, secretion, and excretion. Identify appropriate metabolic waste products present in the feces.

2. For carbohydrates, differentiate the processes of ingestion, digestion, absorption, secretion, and excretion, including the location in the tract where each process occurs. Repeat the analysis for proteins and fats.

3. Identify the approximate normal volumes of fluid entering and leaving the gastrointestinal tract daily.

4. Define the major characteristics and temporally relate the cephalic, gastric, and intestinal phases of tract regulation.

5. Describe the four classes of luminal stimuli that trigger reflexes.

6. Describe the histoanatomical characteristics of the enteric nervous system. Given either a cross section or a longitudinal section of the intestine, name and locate the myenteric and submucosal plexus.

7. Contrast the sympathetic and parasympathetic modulation of the enteric nervous system and the effector organs of the tract.

8.   Classify the following enteric nervous system neurotransmitters as excitatory or inhibitatory: norepinephrine, acetylcholine, CCK, VIP, histamine, and somatostatin.

9. Describe the terms �long reflex� and �short reflex� with respect to the tract.

10. Describe the similarities and differences in regulating gastrointestinal function by nerves, hormones, and paracrine regulators. Include receptors, proximity, and local vs. global specificity.

11. Identify the cell type and anatomical location of the endocrine cells secreting gastrin, secretin, and cholecystokinin (CCK), P, and motilin.

12. Identifiy families to which gastrin, secretin, and CCK and other (non-) hormones belong.

13. Define the concept of �incretins,� and state two gastrointestinal hormones believed to function in this manner.

14. Describe function of somatostatin and histamine as paracrine regulators of acid secretion in the stomach.

Salivary Glands

15. Contrast the plasma and saliva concentrations of Na⁺, Cl^-, and HCO₃^- at low secretion rates and at high secretion rates and the principal cell types involved in each secretion rate.

16. State the substrates and digestion products of salivary amylase (ptyalin).

17. Identify the stimuli and cell types involved in secretion of mucous, and identify the function of salivary mucus.

18. State three types of stimuli that increase salivary secretion.

19. State the components of the saliva important in oral hygiene, and identify the role of salivary secretions in eliminating heavy metals.

Esophagus

20. Identify the normal resting esophageal pressure and explain why this pressure varies with the respiratory cycle.

21. Describe the origin and consequence of the high basal tone found in the upper esophageal sphincter (UES) and lower esophageal sphincter (LES).

22. State the stimulus that initiates the swallowing sequence. Identify the point at which the swallowing sequence becomes automatic (independent of voluntary control).

23. Contrast the patterns of external and internal innervations of the upper, middle, and lower esophagus.

24. Describe the pressure changes that occur in the esophagus as a bolus of food moves from the pharynx to the stomach, including the pressures immediately oral and aboral to the bolus, and the pressures in the upper and lower esophageal sphincters.

25. Contrast primary and secondary peristalsis based on initiating event, voluntary control, reflex propagation, and regions of the pharynx and esophagus involved.

26. Contrast the lower espohageal tone, innervation, and motility defects that lead to heartburn with those leading to achalasia.

Stomach

27. Describe the storage, digestion, and motility roles of the stomach.

28. Contrast the Na⁺, K⁺, and Cl^- concentrations of gastric secretion with that of plasma at low and at high gastric secretion rates. Identify the cell types that mediate this change.

29. Identify the protein component of chief cell secretions.

30. Describe the generation of an �alkaline tide� in the hepatic portal venous system following ingestion of a meal.

31. Describe the role, if any, of HCl in the gastric digestion of carbohydrates, proteins, and fats.

32. Describe the pH of the stomach in the fasted state, and outline the time course and causes of the pH changes in the two hours after ingestion of a protein meal.

33. State the stimuli for pepsinogen release and the mechanism for activating pepsinogen, and describe the digestion products of pepsin activity.

34. Describe the role of the stomach in preventing pernicous anemia.

35. Describe the regulation of H⁺-K⁺ ATPase, the stimuli for activation, and process of activation, including vesicular fusion with the luminal plasma membrane.

36. Describe the mechanism of gastric H⁺ generation and secretion, including the role of K⁺, Cl‑HCO₃, carbonic anhydrase, H⁺-K⁺ ATPase and Na⁺-K⁺ ATPase.

37. Describe the modulation of gastric acid secretion by the enterochromafin-like cell (ECL cell) and the control of this process (including potentiation) by vagal stimulation, gastrin, histamine, and somatostatin.

38. Describe the pathways, if any, for the gastric absorption of electrolytes, water, lipids, amino acids, and carbohydrates.

39. State the mechanism for damage to the gastric mucosal barrier by aspirin, bile acids, andHeliobacter pylori.

40. Identify the stimuli that a) increase gastrin release and b) inhibit gastrin release.

41. State the effects of acid, fat, and solutions of high osmolarity in the duodenum on gastric secretion, and describe the mechanisms by which these effects regulate gastric secretion.

42. Define receptive relaxation of the stomach and state mechanism and consequence.

43. Describe origin and form of electrical activity and the progression of peristaltic waves across the body and antrum of the stomach. Include their role in mixing and propulsion of gastric contents and how the frequency is altered by the volume of gastric contents.

44. Predict the effects of a) meal content (osmolarity, fat content, etc.), b) particle size, and c) volume on the rate of gastric emptying, including duodenal feedback.

45. Describe the causes of peptic ulcer disease.

Pancreas

46. List the major ionic and peptide/protein components secreted by the pancreas. Contrast the plasma and pancreatic concentrations of Na⁺, Cl^-, and HCO₃^- at low secretion rates and at high secretion rates and the principal cell types involved in each secretion rate.

47. Describe the mechanisms by which chyme from the stomach is neutralized in the duodenum.

48. Describe the mechanism by which pancreatic zymogens are activated in the small intestine.

49. List the stimuli that release a) secretin and b) CCK and the cellular mechanisms by which these agents control pancreatic secretion. Include any synergistic effects between CCK and secretin.

50. Describes the role of CFTR in pancreatic ductular secretion, and predict the consequences of cystic fibrosis on the system.

51. State the effects of the autonomic nerves to the pancreas and vago-vagal reflexes on pancreatic secretion.

Bile

52. List the water, ionic, bile salt, and bilirubin components of bile as secreted by the liver, and explain the modification of bile as it is stored in the gall bladder. Identify the role of secretin on the hepatic production of bile.

53. Describe the cellular mechanisms for the hepatic uptake, conjugation, and secretion of bile salts and bilirubin.

54. Describe the role of CCK in causing release of bile from the gall bladder, including the effects on the sphincter of Oddi.

55. Describe the amphipathic structure of bile acids, and predict how this property assists the digestion of fats.

56. State the difference between primary and secondary bile acids.

57. Contrast the physical state of an emulsion with a micellar solution, and explain the conditions for the formation of emulsifications and miceles in the duodenum.

58. Define enterohepatic circulation.

59. Describe the mechanism of reabsorption of bile acids in the early portion of the small intestine with the mechanism found in the later part of the small intestine.

60. Predict the effects of an increase in hepatic portal vein bile acid concentration on the rate of bile secretion, bile acid synthesis, and diseases of the gallbladder.

Small Intestine

61. Describe the role of the microvilli, the unstirred layer, and tight junctions in determining the rate at which glucose, amino acids, water, lipids, and electrolytes are absorbed.

62. List the chemical classes of the carbohydrates entering the duodenum from the stomach, and identify mechanisms mediating further digestion and absorption across the apical and basolateral membranes of the intestinal epithelia. Include pancreatic secretions and brush-border enzymes.

63. Predict the small intestine and colonic consequence of a deficiency in the enzyme lactase, and identify ethnic groups who commonly exhibit this deficiency.

64. List the chemical classes of the proteins entering the duodenum from the stomach, and identify mechanisms mediating further digestion and absorption across the apical and basolateral membranes of the intestinal epithelia. Include pancreatic secretions and brush-border enzymes.

65. Contrast the secondary active transport of amino acids with that of di- and tri-peptides, including the ion used as the energy source.

66. List the chemical classes of the lipids entering the duodenum from the stomach, and identify mechanisms mediating further digestion and absorption across the apical and basolateral membranes of the intestinal epithelia. Include the roles of pancreatic lipase, colipase, and micelles.

67. Describe the role of the endoplasmic reticulum in processing lipids absorbed across the apical membrane of enterocytes.

68. Describe the composition and formation of chylomicrons, their movement across the enterocyte basolateral membrane, and the route of entry into the cardiovascular system.

69. Predict the effects of steatorrhea on the absorption of fat-soluble vitamins.

70. Describe the absorption of water-soluble vitamins, including the role of intrinsic factor in the absorption of vitamin B₁₂.

71. Describe the changes in osmolarity that occur in chyme as it passes from the stomach through the duodenum and colon, and identify the cause of this change.

72. Describe the pathways, if any, by which sodium ions, water, iron, and calcium are absorbed in the small intestine and colon.

Large Intestine

73. Diagram the cellular mechanisms of colonic sodium, potassium, and bicarbonate secretion and the regulation of this process by aldosterone.

74. Define �dietary fiber� and list sources commonly found in the US diet.

75. Identify substrates and products of colonic bacterial metabolism, and predict the impact of metabolites on the rate and composition of intestinal gas formation (flatus).

76. Describe the production and absorption of short chain fatty acids in the colon.

Intestinal Motility

77. Describe the characteristics of the basic electrical rhythm (BER) of the small intestine and its relation to smooth muscle contractile activity.

78. Describe the role of �interstitial cells of Cajal� in generation of electrical slow waves, and predict the consequence of the frequency gradients of electrical slow waves occurring within the intestinal tract.

79. Explain the functional significance of ongoing activity of enteric inhibitory motor neurons to intestinal circular muscle.

80. Contrast the patterns of intestinal motility seen during the absorptive phase (segmentation) with that of the post-absorptive phase between meals [the migrating motility complex (MMC)].

81. Contrast the effects of parasympathetic and sympathetic nervous activity in modulating small intestinal motility.

82. Describe the effects of distension on small intestinal motility.

83. Describe effects of increased pressure in the ileum and cecum on the ileocecal sphincter, including defining the term �gastroileal reflex.�

84. Compare colonic motor activity with the motor activity in the small intestine.

85. Contrast the colonic motor activity during a �mass movement� with that during haustral shuttling and the consequence of each type of colonic motility.

86. Describe the sequence of events occurring during reflexive defecation, differentiating those movements under voluntary control and those under intrinsic control.

Endocrinology

General Principles

1. Explain the principle of negative feedback control of hormone secretion.

2. Explain the principles of positive feedback and feed forward control of hormone secretion.

3. Explain the bases of hormone measurements; e.g., radio-immuno assay, ELISA.

4. Contrast the terms endocrine, paracrine, and autocrine based on the site of hormone release and the pathway to the target tissue. Provide an example of each, and describe major differences in mechanisms of action of peptides working through membrane receptors and steroids, vitamin D, and thyroid hormones working through nuclear receptors.

5. Define hormone, target cell, and receptor.

6. Compare and contrast hormone actions that are exerted through changes in gene expression with those exerted through changes in protein phosphorylation.

7. Understand the effects of plasma hormone binding proteins on access of hormones to their sites of action and degradation and on the regulation of hormone secretion.

8. Explain the effects of secretion, excretion, degradation, and volume of distribution on the concentration of a hormone in blood plasma.

Pituitary Gland � Posterior

9. Contrast the anterior and posterior pituitary lobes with respect to cell types, vascular supply, development, and innervation.

10. List the target organs or cell types for oxytocin and describe its effects on each.

11. Name the stimuli for oxytocin release during parturition or lactation.

12. List the target cells for vasopressin and explain why vasopressin is also known as antidiuretic hormone.

13. Describe the stimuli and mechanisms that control vasopressin secretion

14. Identify disease states caused by a) over-secretion, and b) under-secretion of vasopressin and list the principle symptoms of each.

Pituitary Gland � Anterior

15. Describe the biosynthesis, structure, and actions of the glycoprotein hormones FSH, LH, and TSH.

16. Describe the biosynthesis, structure, actions, and metabolism of the GH/prolactin family.

17. Describe the biosynthesis, structure, and actions of the POMC family: ACTH, MSH, beta-lipoprotein, beta-endorphin.

18. Identify appropriate hypothalamic factors that control the secretion of each of the anterior pituitary hormones, and describe their route of transport from the hypothalamus to the anterior pituitary.

19. Diagram the short-loop and long-loop negative feedback control of anterior pituitary hormone secretion. Predict the changes in secretory rates of hypothalamic, anterior pituitary, and target gland hormones caused by over-secretion or under-secretion of any of these hormones or receptor deficit for any of these hormones.

20. Explain the importance of pulsatile and diurnal secretion.

Thyroid Gland

21. Identify the steps in the biosynthesis, storage, and secretion of tri-iodothyronine (T₃) and thyroxine (T₄) and their regulation.

22. Define �iodine pool�. Describe the distribution of iodine and the iodide metabolic pathway. Relate the distribution of radioiodide in the body to thyroid hormone synthesis, metabolism, and excretion.

23. Describe factors that control the synthesis, storage, and release of thyroid hormones. Explain the importance of thyroid hormone binding in blood on free and total thyroid hormone levels.

24. Understand the significance of the conversion of T₄ to T₃ and reverse T₃ (rT₃) in extra-thyroidal tissues.

25. Describe the actions of thyroid hormones on development and metabolism.

26. Understand the causes and consequences of a) over-secretion and b) under-secretion of thyroid hormones. Explain why either condition can cause an enlargement of the thyroid gland.

Parathyroid Gland, Ca⁺⁺ and PO₄^-

27. Know the cells of origin for parathyroid hormone, its biosynthesis, and mechanism of transport within the blood (bound or free).

28. List the target organs and cell types for parathyroid hormone and describe its effects on each.

29. Describe the functions of the osteoblasts and the osteoclasts in bone remodeling and the factors that regulate their activities.

30. Identify the time course for the onset and duration for each of the biological actions of parathyroid hormone.

31. Describe the regulation of parathyroid hormone secretion and the role of the calcium-sensing receptor.

32. Understand the causes and consequences of a) over-secretion, and b) under-secretion of parathyroid hormone.

33. Identify the sources of vitamin D and diagram the biosynthetic pathway and the organs involved in modifying it to the biologically active 1,25(OH₂)D₃ (1-25 dihydroxy cholecalciferol).

34. Identify the target organs and cellular mechanisms of action for vitamin D.

35. Describe the negative feedback relationship between the parathyroid hormone and the biologically active form of vitamin D [1,25(OH₂)D₃].

36. Describe the consequences of vitamin D deficiency and vitamin D excess.

37. List the cell of origin and target organs or cell types for calcitonin.

38. Name the stimuli that can promote secretion of calcitonin.

39. Describe the actions of calcitonin and identify which (if any) are physiologically important.

Adrenal Gland

40. Identify the functional zones (one medullary and three cortical zones), innervation, and blood supply of the adrenal glands and the principal hormones secreted from each zone.

41. Describe the biosynthesis of the adrenal steroid hormones (glucocorticoids, mineralocorticoids, and androgens) and the key structural features that distinguish each class.

42. Understand the cellular mechanism of action of adrenal cortical hormones.

43. Identify the major actions of glucocorticoids on metabolism and the target organs on which they are produced.

44. Describe the actions of glucocorticoid hormones in injury and stress.

45. Describe the components of the neuroendocrine axis that control glucocorticoid secretion and describe how factors in the internal and external environment influence the neuroendocrine axis.

46. Identify the causes and consequences of a) over-secretion and b) under-secretion of glucocorticoids and adrenal androgens.

47. List the major mineralocorticoids and identify their biological actions and target organs or tissues.

48. Name the physiological stimuli that cause increased mineralocorticoid secretion. Relate these stimuli to regulation of sodium and potassium excretion. List the factors can modulate the secretory response and explain how they are detected.

49. Identify the causes and consequences of a) over-secretion and b) under-secretion of mineralocorticoids.

50. Diagram the negative feedback control of aldosterone secretion.

51. Identify the chemical nature of catecholamines, their biosynthesis, mechanism of transport within the blood, and how they are degraded and removed from the body. Identify how the structure of norepinephrine differs from epinephrine.

52. Describe the biological consequences of activation of the adrenal medulla and identify the target organs or tissues for catecholamines along with the receptor subtype that mediates the response. Understand the mechanism by which epinephrine and norepinephrine can produce different effects in the same tissues. Explain the change in the ratio of epinephrine to norepinephrine release from the adrenal medulla during sympathetic activation (fight and flight), or in prolonged food deprivation.

53. Name the key stimuli causing catecholamine secretion. List the factors that can modulate a) the secretory response and b) the responses of target tissues.

54. Describe the interactions of adrenal medullary and cortical hormones in response to stress.

55. Identify disease states caused by an over-secretion of adrenal catecholamines.

Pancreas

56. Identify the major hormones secreted from the endocrine pancreas, their cells of origin, and their chemical nature.

57. List the target organs or cell types for glucagon and describe its principal actions on each.

58. Identify the time course for the onset and duration of the biological actions of glucagon.

59. Describe the control of glucagon secretion.

60. List the major target organs or cell types for insulin, the major effects of insulin on each, and the consequent changes in concentration of blood constituents.

61. Identify the time course for the onset and duration for the biological actions of insulin.

62. Understand the relationship between blood glucose concentrations and insulin secretion. Describe the roles of neural input and gastrointestinal hormones on insulin secretion. List the factors that modulate the secretory response.

63. Identify disease states caused by: a) over-secretion, b) under-secretion of insulin, or c) decreased sensitivity to insulin, and describe the principal symptoms of each.

Growth

64. Describe the relationship between growth hormone and the insulin-like growth factors and their binding proteins in the regulation of growth.

65. Understand the regulation of growth hormone secretion. Identify the roles of hypothalamic factors and IGF-I.

66. Identify the target organs or cell types for insulin-like growth factors that account for longitudinal growth.

67. Explain how thyroid, gonadal, and adrenal hormones modulate growth.

68. Understand the nature and actions of local growth factors: epidermal growth factor, nerve growth factor, platelet-derived growth factor, and angiogenic and antiangiogenic factors.

Endocrine Integration of Energy and Electrolyte Balance

69. Identify the normal range of plasma glucose concentrations, and list the chemical forms and anatomical sites of storage pools for glucose and other metabolic substrates.

70. Identify the hormones that promote the influx and efflux of glucose, fat, and protein into and out of energy storage pools and their impact on the uptake of glucose by tissues. Establish specific roles for insulin, glucagon, glucocorticoids, catecholamines, growth hormone, and thyroid hormone.

71. Describe the changes in metabolic fuel utilization that occur in long- and short-term fasting and in acute and sustained exercise. Understand how increases or decreases in hormone secretion produce these changes.

72. Describe the role of appetite and metabolic rate in the maintenance of long-term energy balance and fat storage. Identify the factors that regulate appetite and fuel oxidation.

73. Identify the normal range of dietary sodium intake, sodium distribution in the body, and routes of sodium excretion. Explain the roles of antidiuretic hormone, aldosterone, angiotensin, and atrial natriuretic hormone in the regulation of sodium balance.

74. Identify the normal range of dietary potassium intake, potassium distribution in the body, and routes of potassium excretion. Explain how acute changes in aldosterone, insulin, and acid/base concentrations affect the plasma potassium concentration and the movement of potassium into and out of the intracellular compartment. Explain the chronic regulation of body potassium balance and plasma potassium levels by aldosterone through its actions on renal excretion, intestinal excretion, and dietary appetite/absorption.

75. Identify the normal range of dietary calcium intake, calcium distribution in the body, and routes of calcium excretion. Explain the regulation of the plasma calcium concentration by parathyroid hormone, vitamin D, and calcitonin based on exchange with bone, renal excretion, and intestinal excretion and/or absorption.

76. Identify the normal range of dietary phosphate intake, phosphate distribution in the body, and routes of phosphate excretion. Explain the regulation of the plasma phosphate concentration by parathyroid hormone, vitamin D, and calcitonin based on exchange with bone, renal excretion, intestinal excretion and/or absorption.

Reproductive Physiology

Reproductive Physiology � Male

77. Describe the physiological functions of the major components of the male reproductive tract.

78. Describe spermatogenesis and the role of different cell types in this process.

79. Describe the endocrine regulation of testicular function: the role of the GnRH pulse generator, FSH, LH, testosterone, and inhibin.

80. Identify the cell of origin for testosterone, its biosynthesis, mechanism of transport within the blood, how it is metabolized and how it is eliminated. List other physiologically produced androgens.

81. List the target organs or cell types for testosterone and describe its effects on each.

82. Describe the cellular mechanisms of action for testosterone.

83. List the neural, vascular, and endocrine components of the erection and ejaculation response.

84. Identify the causes and consequences of over-secretion and under-secretion of testosterone for a) prepubertal and b) postpubescent males.

85. Compare and contrast the actions of testosterone, dihydrotestosterone, estradiol, and M�llerian inhibitory factor in the development of the male and female reproductive tracts.

Reproductive System � Female

86. Describe oogenesis and its relationship to changes in the ovarian follicle. Explain the roles of FSH, LH, estradiol, inhibin, and paracrine agents in oogenesis and follicular maturation.

87. Describe ovulation and the formation and decline of the corpus luteum and the roles of pituitary hormones in each of these processes.

88. Describe the hormonal regulation of estrogen and progesterone biosynthesis and secretion by the ovary. Identify the cells responsible for their biosynthesis, the mechanism of their transport in the blood, and how they are degraded and removed from the body.

89. List the target organs or cell types for estrogen action and describe its effects on each.

90. Describe the cellular mechanisms of action for estrogen.

91. List the principal physiological actions of progesterone, its target organs or cell types, and describe its effects on each and the importance of �estrogen priming.�

92. Describe the cellular mechanisms of action for progesterone.

93. With time on the x-axis, diagram the changes in the endometrium and the ovary seen during the menstrual cycle and correlate these changes with changes in blood levels of FSH, LH, estradiol, progesterone, and inhibin. Describe how the changes in ovarian steroids produce the proliferative and secretory phases of the uterine endometrium and menstruation and the changes in basal body temperature during the menstrual cycle.

94. Trace the pathways of sperm and egg transport that can result in fertilization and the movement of the fertilized embryo to the uterus.

95. List the protein hormones secreted by the placenta and describe the role of human chorionic gonadotropin (hCG) in the rescue of the corpus luteum in maintaining pregnancy early post-implantation.

96. Describe the interactions between the placenta and the fetal adrenal cortex in the production of estrogens during pregnancy.

97. Discuss the roles of oxytocin, relaxin, and prostaglandins in the initiation and maintenance of parturition.

98. Explain the role of estrogens, progesterone, placental lactogen, prolactin, and oxytocin in mammary gland development during puberty, pregnancy, and lactation.

99. Explain the basis for the inhibition of milk secretion during pregnancy and the initiation of lactation after parturition.

100. Differentiate between milk secretion and milk ejection, and describe the hormonal regulation of both during lactation, including the role of suckling.

101.Explain the physiological bases for the antifertility actions of contraceptive steroid hormones.

102. Describe the age-related changes in the male and female reproductive systems, including the mechanisms responsible for these changes, at the following times:        a. In utero development
b. Puberty
c. Senescence

Integrative Physiology

Thermoregulation

1. Diagram the thermal balance for the body, including heat production (metabolism, exercise, shivering) and heat loss (convection, conduction, radiation, and evaporation). Identify those mechanisms that shift from heat production to heat loss when environmental temperature exceeds body core temperature.

2. Define the thermoregulatory set point. Diagram the negative feedback control of body core temperature, including the role of the hypothalamic set point.

3. Contrast the stability of body core with that of skin temperature. Include the role of cutaneous blood flow and sweating on skin temperature.

4. Identify the mechanisms for maintaining thermal balance in the following environments: desert (120�F), snow skiing (10�F), falling through ice into a lake (water temp 37�F), and snorkeling in 80�F water.

5. Explain how the change in core temperature that accompanies exercise differs from the change in core temperature produced by influenza, which alters the thermoregulatory set point.

6. List and describe the physiological changes that occur as a result of acclimatization to heat and cold.

Exercise

7. Contrast the normal distribution of cardiac output with the distribution of cardiac output during aerobic (sustained) exercise and anaerobic (brief maximal burst) exercise. Include the local regulation of blood flow and the role of capillary reserve in altering skeletal muscle blood flow.

8. Define Vo_2max and identify situations in which it is limited by cardiac output and by pulmonary gas exchange.

9. Explain the control mechanism by which an increase in minute ventilation and heart rate accompanies exercise and how it can occur without any measurable change in arterial blood gas values.

10. Define the effects of training on the heart and coronary circulation and how these changes contribute to an increase in Vo_2max.

11. Explain how each of the following can alter exercise performance: muscle fatigue, Vo_2max, anaerobic threshold, gender, and age.

12. Describe how chronic physical activity alters insulin sensitivity and glucose entry into cells.

13. Describe the health benefits of exercise training on the cardiovascular, musculoskeletal, immune systems, and for weight control.

High Altitude

14. Predict the changes in arterial blood gases and acid base balance that occur in subjects ascending from sea level to 14,000 ft. above sea level (e.g., Pike�s Peak in Colorado).

15. Describe the physiological and hormonal responses that are adaptive to long term residency at high altitude.

16. Contrast adaptations to hypoxia evident in chronic lung disease and high altitude.

Diving

17. Describe the diving reflex exhibited by human infants and some adults when submerged.

18. Explain how children have survived being completely submerged in cold water for over 30 minutes.

19. Describe the changes in hydrostatic pressure during deep dives and the pathophysiology of decompression sickness and nitrogen narcosis.