CV 4. Be able to differentiate between flow and velocity in terms of units and in terms of concept. (G. Ch 14)

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1 ENTRY LEVEL In bold: Literature references to textbooks that will be used in the courses. G = Guyton, 10 th edition A = Alberts, Molecular Biology of the Cell (this textbook is freely accessible online at B = Braunwald's Heart Disease 6/7th edition or e-book Blood & Fluid Dynamics CV 1. Describe the components of blood (cells, ions, proteins, platelets) giving their normal values. Relate the three red blood cell concentration estimates, red blood cell count, hematocrit, and hemoglobin concentration. (G. Ch 32) CV 2. Identify the source, stimulus for formation, and function of the hormone erythropoietin. Relate the rate of red blood cell synthesis to the normal red blood cell life span and the percentage of immature reticulocytes in the blood. (G. Ch 32) CV 3. Know how pressures arise from a hydrostatic column. Apply this to the choice of a reference point for physiological pressure measurement. (G. Ch 14) CV 4. Be able to differentiate between flow and velocity in terms of units and in terms of concept. (G. Ch 14) CV 5. Understand the relationship between pressure, flow, and resistance in the vasculature. Relate this relationship to the (density of) arteries, arterioles, capillaries, venules, and veins. Explain how blood flow to any organ is altered by changes in resistance to that organ. (G. Ch 14) CV 6. Explain how Poiseuille s Law relates resistance to flow. Use it to calculate changes in resistance in a rigid tube as a model for a blood vessel. Discuss the assumptions of the Poisseuille law and explain the deviations from Poiseuille s law that occur in distensible blood vessels. (G. Ch 14, p. 150) CV 7. Understand the relationship between flow, velocity, and cross-sectional area and the influence of vascular compliance. Apply this relationship to the various segments of the circulation. (G. Ch 14) CV 8. Define resistance and conductance. Understand the effects of adding resistance in series vs. in parallel to total resistance. Apply this concept to the redistribution of flow from the aorta to the tissues during exercise. (G. Ch 14) CV 9. List the factors that shift laminar flow to turbulent flow. Describe the relationship between velocity, viscosity, and audible events, such as murmurs and bruits. (G. Ch 14) CV 10. 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. (G. Ch 15) CV 11. Explain how hemodynamics in blood vessels, especially the microcirculation, deviates from theory due to anomalous viscosity, distensibility, axial streaming, and critical closing behaviour. (G. Ch 16) PhD-training course Vascular Biology 1

2 Arterial Pressure and the Circulation CV 12. Describe the organization of the circulatory system and explain how the systemic and pulmonary circulations are linked physically and physiologically. (G. Ch 14) CV 13. Explain how the physical properties of the circulation (vessel size, wall thickness, wall composition, compliance, elastic recoil, and blood viscosity) affect movement of blood and delivery of nutrients. (G. Ch 14) CV 14. Describe blood pressure measurement with a catheter and transducer and explain the components of the blood pressure waveform. Contrast that with the indirect estimation of blood pressure with a sphygmomanometer. Explain how each approach provides estimates of systolic and diastolic pressures. Given systolic and diastolic blood pressures, calculate the pulse pressure and the mean arterial pressure. (G. Ch 15) CV 15. 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. (G. Ch 15) CV 16. Contrast pressures and oxygen saturations in the arteries, arterioles, capillaries, venules, and veins of both the systemic and pulmonary circulations. Repeat that process for velocity of blood flow and cross-sectional area, and volume. (G. Ch 15) CV 17. Identify the cell membrane receptors and second messenger systems mediating the contraction of vascular smooth muscle by norepinephrine, angiotensin II, and vasopressin. (G. Ch 18, 19) CV 18. Identify the cell membrane receptors and second messenger systems mediating the relaxation of vascular smooth muscle by nitric oxide, bradykinin, prostaglandins, and histamine (G. Ch 17) The Microcirculation and Lymphatics CV 19. 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 flowlimited exchange. (G. Ch 16) CV 20. Describe how changes in capillary surface area affect the capacity for fluid exchange. (G. Ch 16) CV 21. Define the Starling equation and discuss how each component influences fluid movement across the capillary wall (G. Ch 16, p. 170). CV 22. Describe the pathway for leukocyte migration across the microcirculation, including expression of cellular adhesion molecules, and recognition sites in the vascular endothelial cells. (G. Ch 33) CV 23. Starting at the post-capillary venule, describe the process of angiogenesis, including the stimulus that initiates new vessel growth. (A, use search function) CV 24. Describe the Donnan effect and its importance in capillary dynamics. (G. Ch 25, p. 266) PhD-training course Vascular Biology 2

3 CV 25. 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. (G. Ch 16) CV 26. Using the components of the Starling equation, explain why fluid does not usually accumulate in the interstitium of the lungs. (G. Ch 16) CV 27. Describe how histamine alters the permeability of the post-capillary venules, and how the loss of albumin into the interstitial space promotes localized edema. (G. Ch 16, 17) CV 28. Describe the lymphatics, and explain how the structural characteristics of terminal lymphatics allow the reabsorption of large compounds, such as proteins. (G. Ch 16) CV 29. Contrast the structure of lymphatic capillaries and systemic capillaries, including the significance of the smooth muscle in the walls of the lymphatic vessels. (G. Ch 16) CV 30. Identify critical functions of the lymphatic system in fat absorption, interstitial fluid reabsorption, and clearing large proteins from the interstitial spaces. (G. Ch 16) CV 31. Diagram the relationship between interstitial pressure and lymph flow. Explain why edema does not normally develop as interstitial pressure increases. (G. Ch 16) CV 32. 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. (G. Ch 16) CV 33. Explain how inflammatory cells adhere to the vessel wall, migrate into the vessel wall and locate to certain regions in atherosclerotic vessels (Nature (2000) 407:233) CV 34. Describe the effect of shear stress on local gene expression and plaque formation in atherosclerotic vessels (Nature (2000) 407:233) Regulation of Arterial Pressure (G. Ch 18) CV 35. List the anatomical components of the baroreceptor reflex. CV 36. 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. CV 37. 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. CV 38. 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. CV 39. Contrast the relative contribution of short- and long-term mechanisms in blood pressure and blood volume regulation. CV 40. Outline the cardiovascular reflexes initiated by decreases in blood O 2 and increases in blood CO 2. PhD-training course Vascular Biology 3

4 CV 41. Describe the release, cardiovascular target organs, and mechanisms of cardiovascular effects for angiotensin, atrial natriuretic factor, bradykinin, and EDRF (endothelial-derived relaxing factor). Local Control of Blood Flow CV 42. Define autoregulation of blood flow in the brain. Compare and contrast the myogenic and metabolic theories of autoregulation. Identify which mechanism would predominate at high and low mean arterial pressures. (G. Ch 61, p. 710) CV 43. Describe how the theory of metabolic regulation of blood flow accounts for active hyperemia and reactive hyperemia. (G. Ch 17) CV 44. Identify the role of Po 2, Pco 2, ph, adenosine, and K + in the metabolic control of blood flow to specific tissues. (G. Ch 21, p 224, C. 17) CV 45. Diagram the synthetic pathway for nitric oxide (EDRF, endothelial derived relaxing factor), including substrate and the interplay between endothelium and vascular smooth muscle. (G. Ch 17) CV 46. Discuss the circumstances and the mechanisms whereby humoral substances contribute to regulation of the microcirculation. (G. Ch 17) CV 47. Discuss the interaction of a) intrinsic (local), b) neural, and c) humoral control mechanisms, and identify one situation in which each dominates the regulation of blood flow to a tissue. (G. Ch 17) CV 48. Describe the role of angiogenesis in providing a long-term match of tissue blood flow and metabolic need. (G. Ch 17) Metabolism CV 49. Describe the synthesis and metabolic pathways of chylomicrons, LDL and HDL, including their apoproteins. (G. Ch 68) CV 50. Describe the roles of LDL receptor, lipoprotein lipase, cholesterol ester transfer protein and ABC-proteins. (G. Ch 68) CV 51. Describe the basic physiology of glucose metabolism, and the defects in type 1 and type 2 diabetes mellitus. (G. Ch 78) CV 52. Contrast absence of insulin and insulin resistance. (Büller, p 81) CV 53. Describe the components of the metabolic syndrome. (Büller, p 81) GENOMICS (A.) CV 54. Describe the formation of mrna by DNA. Describe the difference between introns and exons, between immature and mature RNA, between rrna, trna and mrna CV 55. Describe how the entire genome can be studied. What techniques need to be used for validating differentially changed genes. CV 56. What is the difference between Northern, Western and Southern blots. PhD-training course Vascular Biology 4

5 CV 57. What is the principle of immunohistochemistry. Describe all necessary steps in relation to an example of your own work. PhD-training course Vascular Biology 5