Vascular Physiology

1. Vascular Physiology Gregory Shen (沈啸), MD Department of Physiology Room 516, Research Building C School of Medicine, Zijingang Campus Email: shenx@zju.edu.cn

2. Tunica media Smooth muscle Tunica externa Adventitia

6. Elastic fibers • Accounts for most of the stretch of vessels as well as other tissues (e.g., lungs). • Composed of a core of elastin and a covering of microfibrils. • Covalently corss-link and assemble into a highly elastic network of fibers. • In arteries, elastic fibers are arranged as concentric cylindrical lamellae.

7. Collagen fibers • Far less extensible than the elastic fibers. • The basic unit in blood vessels is composed of type I and type III collagen.

9. Because of the elastic properties of vessels, the pressure-flow relationship of passive vascular beds in non-linear ΔP Blood flow = Resistance (R) Rigid tube 8Lη R= πr4 6 Critical closing pressure

10. Elastic and collagen fibers determine the distensibility/compliance of vessels. • Artery has low volume capacity but can withstand large transmural pressure difference. (resistance vessels) • Vein s have a large volume capacity but can withstand small transmural pressure differences. (capacitance vessels) • Compliance (C) = • Difference in compliance cause arteries to act as resistors and veins to act as capacitors. ΔV ΔP

11. Movement of blood into and out of the arteries during the cardiac cycle The blood moved in a single heart contraction stretches out the arteries, so that their recoil continues to push on the blood, keeping it moving during diastole. Progressive and diffuse fibrosis of vessel walls with age reduces the elastic properties and the compliance of arteries. Arteriosclerotic change gives rise to larger pulse pressure.

12. Artery blood pressure

13. Systolic pressure (SP，收缩压): the maximum arterial pressure reached during peak ventricular ejection Diastolic pressure (DP，舒张压): the minimum arterial pressure just before ventricular ejection begins Pulse pressure (PP，脉压): the difference between SP and DP Mean arterial pressure (MAP，平均动脉压): the average pressure in the cardiac cycle (=DP+1/3PP) or (=2/3DP+1/3SP)

14. Physiological indications of MAP and PP MAP: Is more consistent in large arteries than SP or DP. Does not reflect the compliance of arteries. PP: Reflect the compliance of arteries. e.g., in arteriosclerosis, PP increases.

15. Arterial pulse recorded in different vessels

16. Arterial pulse recorded under different conditions

17. Blood travels from artery to arteriole to capillary to venule to vein

18. Arterioles（微动脉） • Two major roles: • To be responsible for determining the relative blood flow in individual organs at any given MAP • All together, to be a major factor in determining MAP

19. Arterioles • Small precapillary resistance vessels (10-50 μ) composed of an endothelium surrounded by one or more layers of smooth muscle cells • Richly innervated by sympathetic adrenergic fibers and highly responsive to sympathetic vasoconstriction via both α1 and α2 adrenergic receptors • Represent a major site for regulating systemic vascular resistance • Primary function within an organ is flow regulation, thereby determining oxygen delivery and the washout of metabolic by-products • Regulate, in part, capillary hydrostatic pressure and therefore influence capillary fluid exchange

20. Effects of arteriolar vasodilation or vasoconstriction on capillary blood pressure Dynamic changes in vasodilation/vasoconstriction in the arterioles regulate downstream pressures and flow rates.

21. Dynamic adjustments in the blood distribution to the organs is accomplished by relaxation and contraction of circular smooth muscle in the arterioles.

22. Local Control of Blood Flow The mechanism independent of nerves or hormones by which organs and tissues alter their own arteriolar resistances, thereby self-regulating their blood flows • Active hyperemia（主动充血） • Flow autoregulation（血流自身调节） • Reactive hyperemia（反应性充血） • Local response to injury（对损伤的局部反应）

23. Local control of organ blood flow Active hyperemia and flow autoregulation differ in their cause but both result in the production of the same local signals that provoke vasodilation.

24. Reactive hyperemia – When an organ or tissue has had its blood supply completely occluded, a profound transient increase in its blood flow occurs as soon as the occlusion is released

25. Response to injury – Tissue injury causes a variety of substances to be released locally from cells or generated from plasma precursors. These substances make arteriolar smooth muscle relax and cause vasodilation in an injured area

26. Extrinsic Control • Sympathetic nerves（交感神经） • Noncholinergic, nonadrenergic autonomic neurons (NO)（NANC） • Hormones (epinephrine, angiotensin II, vasopressin, atrial natriuretic peptide)

28. 2

29. Renin-angiotensin system（肾素-血管紧张素系统）

30. Vasopressin（血管升压素）

31. Endothelium-derived vasoactive substances Paracrine effect • Vasodilator factors: • NO (produced by eNOS) • PGI2 – prostagladin I2（前列环素） • Vasoconstriction factors: • Endothelin-1 (ET-1)

32. Vasoconstrictor factors – Endothelin-1（内皮素-1）

33. Major factors affecting arteriolar radius

36. Microcirculation（微循环） Function: Transfer of substances between blood & the tissues. *Lined with only one layer of endothelial cells. *The inner size has the width only single red blood cell can pass through.

37. Capillaries lack smooth muscle, but contraction/relaxation of circular smooth muscle in upstream metarterioles and precapillary sphincters (in response to metabolic factors) determine the volume of blood each capillary receives.

38. 2 1 3 A-V shunt 4 5 3 pathways • Circuitous channel (Nutritional channel)（营养通路）

39. 2 1 3 A-V shunt 4 5 • Thoroughfare channel（直捷通路）

40. 2 1 3 A-V shunt 4 5 • Arteriovenous shunt (A-V shunt)（动-静脉短路） Arteriovenous anastomoses

41. Capillaries（毛细血管） • Main function: Exchange of nutrients and metabolic end products

42. Capillary walls are a single endothelial cell in thickness. The capillary is the primary point exchange between the blood and the interstitial fluid (ISF). Intercellular clefts assist the exchange.

43. Structure of capillary wall

44. Relationship between total cross-sectional area and flow velocity Blood flows much slower in capillaries than aorta because they have the largest cross-sectional area. The slow movement of blood allows sufficient exchange of substances between blood and interstitial fluid.

45. The ways substances moving between the blood and interstitial fluid of tissue (across endothelial capillary wall) Diffusion (the most important) • Lipid-soluble substances, including O2 and CO2, diffuse through plasma membrane. • Ions and polar molecules diffuse through water-filled channels (intercellular clefts and fused-vesicle channels). • Some macromolecules (proteins) cross through endothelial endocytosis in the lumen side and exocytosis at the interstitial side (transcytosis). Endocytosis Exocytosis

46. Structure variation of the capillary wall • Continuous: found in muscle, skin, lung, central nervous system • Fenestrated: found in exocrine glands, intestinal mucosa • Discontinuous: found in liver, spleen, bone marrow

47. Bulk flow of protein-free plasma and interstitial fluid Movement of fluid and solutes out of the blood is called filtration. Hydrostatic forces Osmotic forces Movement of fluid and solutes into the blood is called absorption.

48. Net filtration pressure (or Effective filtration pressure)

49. Autoregulation of microcirculation • The contraction of vascular smooth musclethat underlies autoregulation is autonomous, entirely independent of neurnal and endocrine mechanisms. • Both myogenic and metabolic mechansims play an role. • It is important for organs that are very sensitive to ischemia or hypoxia. (brain, heart and kidney) Rigid tube

50. Venous pressure and venous return （静脉血压与静脉回流） A low resistance conduits for blood flow from tissues to the heart. Diameters are reflexively altered in response to changes in blood volume, thereby maintaining venous pressure for blood return to the heart.