AP 151

1. AP 151 Cardiovascular Physiology

2. Walls of arteries and veins contain three distinct layers Tunic intima Tunica media Tunica externa Structure of vessel walls

3. A Comparison of a Typical Artery and a Typical Vein

4. Compared to veins, arteries Have thicker walls Have more smooth muscle and elastic fibers Are more resilient Differences between arteries and veins

5. Undergo changes in diameter Vasoconstriction � decreases the size of the lumen Vasodilation � increases the size of the lumen Classified as either elastic (conducting) or muscular (distribution) Small arteries (internal diameter of 30 um or less) are called arterioles Arteries

6. An endothelial tube inside a basal lamina These vessels Form networks Surround muscle fibers Radiate through connective tissue Weave throughout active tissues Capillaries have two basic structures Continuous Fenestrated Flattened fenestrated capillaries = sinusoids Capillaries

7. Capillary Structure

8. An interconnected network of vessels consisting of Collateral arteries feeding an arteriole Metarterioles Arteriovenous anastomoses Capillaries Venules Capillary Beds

9. The Organization of a Capillary Bed

10. Collect blood from all tissues and organs and return it to the heart Are classified according to size Venules Medium-sized veins Large veins Venules and medium-sized veins contain valves Prevent backflow of blood Veins

11. Total blood volume is unevenly distributed Venoconstriction maintains blood volume Veins are capacitance vessels Capacitance = relationship between blood volume and pressure Distribution of blood

13. Blood Flow Purpose of cardiovascular regulation is the main-tenance of adequate blood flow through the capillaries in peripheral tissues and organs Actual volume of blood flowing through a vessel, an organ, or the entire circulation in a given period: Is measured in ml per min. Is equivalent to cardiac output (CO), considering the entire vascular system Is relatively constant when at rest Varies widely through individual organs, according to immediate needs Is determined by the interplay between pressure (P) and resistance [R]

14. Blood Flow, Blood Pressure, and Resistance Blood flow (F) is directly proportional to the difference in blood pressure (?P) (a pressure differential) between two points in the circulation If ?P increases, blood flow increases If ?P decreases, blood flow declines Blood flow is inversely proportional to resistance (R) If R increases, blood flow decreases If R decreases, blood flow increases R is more important than ?P in influencing local blood pressure In summary, Flow (F) ? DP/R Where ? means �is proportional to� and D means �the difference in�

16. Blood Flow Blood flows through vascular system when there is pressure difference (?P) at its two ends Flow rate is directly proportional to difference (?P = P1 - P2)

17. Flow at Different Points From aorta to capillaries, flow ? for 3 reasons greater distance, more friction to ? flow smaller radii of arterioles and capillaries farther from heart, greater total cross sectional area From capillaries to vena cava, flow ? again large amount of blood forced into smaller channels never regains velocity of large arteries

18. Resistance Resistance � a force that opposes blood flow Measure of the amount of friction blood encounters as it passes through vessels Generally encountered in the systemic circulation Referred to as peripheral resistance (PR) The three important sources of resistance are: Blood viscosity - thickness of blood Normally stable but disorders that affect hematocrit change viscosity and thus peripheral resistance Increase viscosity ? Increase resistance Total blood vessel length Normally constant but may increase with weight gain Increase vessel length ? Increase resistance Blood vessel diameter Most important factor affecting resistance Blood makes more contact with the walls of smaller vessels and thus R is larger

19. Effect of Vessel Diameter on Resistance to Blood Flow Vessel diameter determines how much blood flows through a tissue or organ Vasodilation decreases resistance, increases blood flow Vasoconstriction increases resistance, decreases blood flow Relationship between resistance and vessel diameter is expressed in the following equation where the resistance is inversely proportional to the 4th power of radius: R ? 1/r4 Fatty plaques from atherosclerosis Cause turbulent blood flow Dramatically increase resistance due to turbulence

21. Velocity of Blood Flow Blood velocity: Changes as it travels through the systemic circulation Is inversely proportional to the cross-sectional area Slow capillary flow allows adequate time for exchange between blood and tissues

22. Relationships among Vessel Diameter, Cross-sectional Area, Blood Pressure, and Blood Viscosity

24. Capillary Exchange Only occurs across capillary walls between blood and surrounding tissues 3 routes across endothelial cells intercellular clefts fenestrations through cytoplasm Mechanisms involved diffusion, transcytosis, filtration and reabsorption

25. Capillary Exchange - Diffusion Most important mechanism Lipid soluble substances steroid hormones, O2 and CO2 diffuse easily Insoluble substances glucose and electrolytes must pass through channels, fenestrations or intercellular clefts Large particles - proteins, held back

26. Capillary Exchange - Transcytosis Pinocytosis - transport vesicles across cell - exocytosis Important for fatty acids, albumin and some hormones (insulin)

27. Capillary Exchange - Filtration and Reabsorption Opposing forces blood (hydrostatic) pressure drives fluid out of capillary high on arterial end of capillary, low on venous end colloid osmotic pressure (COP) draws fluid into capillary results from plasma proteins (albumin)- more in blood oncotic pressure = net COP (blood COP - tissue COP) Hydrostatic pressure physical force exerted against a surface by a liquid, (BP is an example)

29. Figure 21.13 Forces Acting across Capillary Walls

30. Causes of Edema ? Capillary filtration (? capillary BP or permeability) poor venous return congestive heart failure - pulmonary edema insufficient muscular activity kidney failure (water retention, hypertension) histamine makes capillaries more permeable ? Capillary reabsorption hypoproteinemia (oncotic pressure ? blood albumin) cirrhosis, famine, burns, kidney disease Obstructed lymphatic drainage

31. Consequences of Edema Tissue necrosis oxygen delivery and waste removal impaired Pulmonary edema suffocation Cerebral edema headaches, nausea, seizures and coma Circulatory shock excess fluid in tissue spaces causes low blood volume and low BP

32. Tissue Perfusion Refers to the blood flow through tissues Factors that affect tissue perfusion include: Cardiac output Peripheral resistance Blood pressure Regulatory mechanism used to control TF Autoregulation Neural mechanisms Endocrine mechanisms

33. Autoregulation of Blood Flow Maintains fairly constant blood flow despite BP variation Involves 2 different mechanisms 1. Myogenic control mechanisms occur in some tissues because vascular smooth muscle contracts when stretched & relaxes when not stretched E.g. decreased arterial pressure causes cerebral vessels to dilate & vice versa 2. Metabolic control mechanism matches blood flow to local tissue needs Low O2, low pH (acidity due to lactic acid) or high CO2 (hypercapnia), or K+ from high metabolism cause vasodilation which increases blood flow (= active hyperemia)

35. Paracrine Regulation of Blood Flow Endothelium produces several paracrine regulators that promote relaxation: Nitric oxide (NO) NO is involved in setting resting �tone� of vessels Levels are increased by Parasymp activity Vasodilator drugs such as nitroglycerin or Viagra act thru NO

36. Sympathetic activation causes increased cardiac output & resistance in periphery & viscera Blood flow to skeletal muscles is increased Because their arterioles dilate in response to epinephrine Thus blood is shunted away from visceral & skin to muscles Neural Regulation of Blood Flow

38. Antidiuretic hormone � released in response to decreased blood volume Angiotensin II � released in response to a fall in blood pressure Erythropoietin � released if BP falls or O2 levels are abnormally low Natriuretic peptides � released in response to excessive right atrial stretch Hormonal Regulation of Tissue Perfusion

40. Circulatory pressure is divided into three components Blood pressure (BP) Arterial pressure, reported in mm Hg Range from about 100 at entrance to aorta to about 35 at start of capillary network Capillary hydrostatic pressure (CHP) Pressure within capillary beds (35 mm at start-18 at end) Venous pressure Pressure within the venous system Low; pressure gradient from venules to right atrium is ca.18 mm Hg ?P across the entire systemic circuit is called the circulatory pressure Averages about 100 mm Hg For circulation to occur, this pressure must be sufficient to overcome the total peripheral resistance- the resistance of the entire cardiovascular system Circulatory Pressure

41. Blood Pressure Force that blood exerts against a vessel wall Measured at brachial artery of arm Systolic pressure: BP during ventricular systole Diastolic pressure: BP during ventricular diastole Normal value, young adult: 120/75 mm Hg Pulse pressure: systolic - diastolic important measure of stress exerted on small arteries Mean arterial pressure (MAP): measurements taken at intervals of cardiac cycle, best estimate: diastolic pressure + (1/3 of pulse pressure) varies with gravity: standing; 62 - head, 180 - ankle

43. BP Changes With Distance

44. Blood Pressure Importance of arterial elasticity expansion and recoil maintains steady flow of blood throughout cardiac cycle, smoothes out pressure fluctuations and ? stress on small arteries BP rises with age: arteries less distensible BP determined by cardiac output, blood volume and peripheral resistance

46. Abnormalities of Blood Pressure Hypertension chronic resting BP > 140/90 consequences can weaken small arteries and cause aneurysms Hypotension chronic low resting BP caused by blood loss, dehydration, anemia

47. Regulation of BP and Flow Local control Neural control Hormonal control

48. Local Control of BP and Flow Metabolic theory of autoregulation tissue inadequately perfused, wastes accumulate = vasodilation Vasoactive chemicals substances that stimulate vasomotion; histamine, bradykinin Reactive hyperemia blood supply cut off then restored Angiogenesis - growth of new vessels regrowth of uterine lining, around obstructions, exercise, malignant tumors controlled by growth factors and inhibitors

49. Neural Control of BP and Flow Vasomotor center of medulla oblongata: sympathetic control stimulates most vessels to constrict, but dilates vessels in skeletal and cardiac muscle integrates three autonomic reflexes baroreflexes chemoreflexes medullary ischemic reflex

50. Neural Control: Baroreflex Changes in BP detected by stretch receptors (baroreceptors), in large arteries above heart aortic arch aortic sinuses (behind aortic valve cusps) carotid sinus (base of each internal carotid artery) Autonomic negative feedback response baroreceptors send constant signals to brainstem ? BP causes rate of signals to rise, inhibits vasomotor center, ? sympathetic tone, vasodilation causes BP ? ? BP causes rate of signals to drop, excites vasomotor center, ? sympathetic tone, vasoconstriction and BP ?

52. BaroreflexNegative Feedback Response

54. Correct ref. Figure # below �hemorrhage�Correct ref. Figure # below �hemorrhage�

56. Neural Control: Chemoreflex Chemoreceptors in aortic bodies and carotid bodies located in aortic arch, subclavian arteries, external carotid arteries Autonomic response to changes in blood chemistry pH, O2, CO2 primary role: adjust respiration secondary role: vasomotion hypoxemia, hypercapnia and acidosis stimulate chemoreceptors, instruct vasomotor center to cause vasoconstriction, ? BP, ? lung perfusion and gas exchange

57. Other Inputs to Vasomotor Center Medullary ischemic reflex inadequate perfusion of brainstem cardiac and vasomotor centers send sympathetic signals to heart and blood vessels ? cardiac output and causes widespread vasoconstriction ? BP Other brain centers stress, anger, arousal can also ? BP

58. Hormonal Control of BP and Flow Aldosterone released in response to low blood volume and pressure promotes Na+ and water retention by kidneys increases blood volume and pressure Atrial natriuretic factor released in response to excessive right atrial stretch ? urinary sodium excretion generalized vasodilation ADH (water retention) released in response to a decrease in blood volume pathologically high concentrations, vasoconstriction Epinephrine and norepinephrine effects most blood vessels binds to ?-adrenergic receptors, vasoconstriction skeletal and cardiac muscle blood vessels binds to ?-adrenergic receptors, vasodilation

59. Angiotensinogen (prohormone produced by liver) ? Renin (kidney enzyme released by low BP) Angiotensin I ? ACE (angiotensin-converting enzyme in lungs) ACE inhibitors block this enzyme lowering BP Angiotensin II very potent vasoconstrictor Hormonal Control of BP and Flow

60. Routing of Blood Flow Localized vasoconstriction pressure downstream drops, pressure upstream rises enables routing blood to different organs as needed Arterioles - most control over peripheral resistance located on proximal side of capillary beds most numerous more muscular by diameter

61. Graphic in proofs looked as if arterioles are EMPTY.Graphic in proofs looked as if arterioles are EMPTY.

62. Blood Flow in Response to Needs Arterioles shift blood flow with changing priorities

63. Mechanisms of Venous Return Pressure gradient 7-13 mm Hg venous pressure towards heart venules (12-18 mm Hg) to central venous pressure (~5 mm Hg) Gravity drains blood from head and neck Skeletal muscle pump in the limbs Thoracic pump inhalation - thoracic cavity expands (pressure ?) abdominal pressure ?, forcing blood upward central venous pressure fluctuates 2mmHg- inhalation, 6mmHg-exhalation blood flows faster with inhalation Cardiac suction of expanding atrial space

64. Skeletal Muscle Pump

66. Venous Return and Physical Activity Exercise ? venous return in many ways heart beats faster, harder - ? CO and BP vessels of skeletal muscles, lungs and heart dilate ? flow ? respiratory rate ? action of thoracic pump ? skeletal muscle pump Venous pooling occurs with inactivity venous pressure not enough force blood upward with prolonged standing, CO may be low enough to cause dizziness or syncope prevented by tensing leg muscles, activate skeletal m. pump jet pilots wear pressure suits

69. Circulatory Changes During Exercise At beginning of exercise, Symp activity causes vasodilation via Epi & local ACh release Blood flow is shunted from periphery & visceral to active skeletal muscles Blood flow to brain stays same As exercise continues, intrinsic regulation is major vasodilator Symp effects cause SV & CO to increase HR & ejection fraction increases vascular resistance

72. Circulatory Shock Any state where cardiac output insufficient to meet metabolic needs cardiogenic shock - inadequate pumping of heart (MI) low venous return (LVR) shock - 3 principle forms hypovolemic shock - most common loss of blood volume: trauma, burns, dehydration obstructed venous return shock tumor or aneurysm venous pooling (vascular) shock next slide

73. LVR Shock Venous pooling (vascular) shock long periods of standing, sitting or widespread vasodilation neurogenic shock - loss of vasomotor tone, vasodilation causes from emotional shock to brainstem injury Septic shock bacterial toxins trigger vasodilation and ? capillary permeability Anaphylactic shock severe immune reaction to antigen, histamine release, generalized vasodilation, ? capillary permeability

75. Special Circulatory Routes- Brain Total perfusion kept constant seconds of deprivation causes loss of consciousness 4-5 minutes causes irreversible brain damage flow can be shifted from one active region to another Responds to changes in BP and chemistry cerebral arteries: dilate as BP ?, constrict as BP rises main chemical stimulus: pH CO2 + H2O ? H2 CO3 ? H+ + (HCO3)- hypercapnia (CO2 ?) in brain, pH ?, triggers vasodilation hypocapnia, ? pH, vasoconstriction occurs with hyperventilation, may lead to ischemia, dizziness and sometimes syncope

76. TIA�s and CVA�s TIA�s - transient ischemic attacks dizziness, loss of vision, weakness, paralysis, headache or aphasia; lasts from a moment to a few hours, often early warning of impending stroke CVA - cerebral vascular accident (stroke) brain infarction caused by ischemia atherosclerosis, thrombosis, ruptured aneurysm effects range from unnoticeable to fatal blindness, paralysis, loss of sensation, loss of speech common recovery depends on surrounding neurons, collateral circulation

77. Special Circulatory Routes -Skeletal Muscle Highly variable flow At rest arterioles constrict, total flow about 1L/min During exercise arterioles dilate in response to epinephrine and sympathetic nerves precapillary sphincters dilate due to lactic acid, CO2 blood flow can increase 20 fold Muscular contraction impedes flow

78. Special Circulatory Routes - Lungs Low pulmonary blood pressure flow slower, more time for gas exchange capillary fluid absorption oncotic pressure overrides hydrostatic pressure Unique response to hypoxia pulmonary arteries constrict, redirects flow to better ventilated region