Cardiac Output, Blood Flow, and Blood Pressure

2. Is volume of blood pumped/min by each ventricle Stroke volume (SV) = blood pumped/beat by each ventricle CO = SV x HR Total blood volume is about 5.5L Cardiac Output (CO)

3. Regulation of Cardiac Rate Without neuronal influences, SA node will drive heart at rate of its spontaneous activity Normally Symp & Parasymp activity influence HR (chronotropic effect) Autonomic innervation of SA node is main controller of HR Symp & Parasymp nerve fibers modify rate of spontaneous depolarization

4. Regulation of Cardiac Rate continued NE & Epi stimulate opening of pacemaker HCN channels This depolarizes SA faster, increasing HR ACH promotes opening of K+ channels The resultant K+ outflow counters Na+ influx, slowing depolarization & decreasing HR

5. Cardiac control center of medulla coordinates activity of autonomic innervation Sympathetic endings in atria & ventricles can stimulate increased strength of contraction Regulation of Cardiac Rate continued

7. Stroke Volume Is determined by 3 variables: End diastolic volume (EDV) = volume of blood in ventricles at end of diastole Total peripheral resistance (TPR) = impedance to blood flow in arteries Contractility = strength of ventricular contraction

8. EDV is workload (preload) on heart prior to contraction SV is directly proportional to preload & contractility Strength of contraction varies directly with EDV Total peripheral resistance = afterload which impedes ejection from ventricle Ejection fraction is SV/ EDV Normally is 60%; useful clinical diagnostic tool Regulation of Stroke Volume

9. Frank-Starling Law of the Heart States that strength of ventricular contraction varies directly with EDV Is an intrinsic property of myocardium As EDV increases, myocardium is stretched more, causing greater contraction & SV

10. Frank-Starling Law of the Heart continued (a) is state of myocardial sarcomeres just before filling Actins overlap, actin-myosin interactions are reduced & contraction would be weak In (b, c & d) there is increasing interaction of actin & myosin allowing more force to be developed

11. Extrinsic Control of Contractility At any given EDV, contraction depends upon level of sympathoadrenal activity NE & Epi produce an increase in HR & contraction (positive inotropic effect) Due to increased Ca2+ in sarcomeres

13. Venous Return Is return of blood to heart via veins Controls EDV & thus SV & CO Dependent on: Blood volume & venous pressure Vasoconstriction caused by Symp Skeletal muscle pumps Pressure drop during inhalation

14. Venous Return continued Veins hold most of blood in body (70%) & are thus called capacitance vessels Have thin walls & stretch easily to accommodate more blood without increased pressure (=higher compliance) Have only 0-10 mm Hg pressure

15. Blood & Body Fluid Volumes

16. Blood Volume Constitutes small fraction of total body fluid 2/3 of body H20 is inside cells (intracellular compartment) 1/3 total body H20 is in extracellular compartment 80% of this is interstitial fluid; 20% is blood plasma

17. Exchange of Fluid between Capillaries & Tissues Distribution of ECF between blood & interstitial compartments is in state of dynamic equilibrium Movement out of capillaries is driven by hydrostatic pressure exerted against capillary wall Promotes formation of tissue fluid Net filtration pressure= hydrostatic pressure in capillary (17-37 mm Hg) - hydrostatic pressure of ECF (1 mm Hg)

18. Exchange of Fluid between Capillaries & Tissues Movement also affected by colloid osmotic pressure = osmotic pressure exerted by proteins in fluid Difference between osmotic pressures in & outside of capillaries (oncotic pressure) affects fluid movement Plasma osmotic pressure = 25 mm Hg; interstitial osmotic pressure = 0 mm Hg

19. Overall Fluid Movement Is determined by net filtration pressure & forces opposing it (Starling forces) Pc + Pi (fluid out) - Pi + Pp (fluid in) Pc = Hydrostatic pressure in capillary Pi = Colloid osmotic pressure of interstitial fluid Pi = Hydrostatic pressure in interstitial fluid Pp = Colloid osmotic pressure of blood plasma

21. Edema Normally filtration, osmotic reuptake, & lymphatic drainage maintain proper ECF levels Edema is excessive accumulation of ECF resulting from: High blood pressure Venous obstruction Leakage of plasma proteins into ECF Myxedema (excess production of glycoproteins in extracellular matrix) from hypothyroidism Low plasma protein levels resulting from liver disease Obstruction of lymphatic drainage

22. Regulation of Blood Volume by Kidney Urine formation begins with filtration of plasma in glomerulus Filtrate passes through & is modified by nephron Volume of urine excreted can be varied by changes in reabsorption of filtrate Adjusted according to needs of body by action of hormones

23. ADH (vasopressin) ADH released by Post Pit when osmoreceptors detect high osmolality From excess salt intake or dehydration Causes thirst Stimulates H20 reabsorption from urine ADH release inhibited by low osmolality

24. Aldosterone Is steroid hormone secreted by adrenal cortex Helps maintain blood volume & pressure through reabsorption & retention of salt & water Release stimulated by salt deprivation, low blood volume, & pressure

25. Renin-Angiotension-Aldosterone System When there is a salt deficit, low blood volume, or pressure, angiotensin II is produced Angio II causes a number of effects all aimed at increasing blood pressure: Vasoconstriction, aldosterone secretion, thirst

26. Fig 14.12 shows when & how Angio II is produced, & its effects Angiotensin II

27. Atrial Natriuretic Peptide (ANP) Expanded blood volume is detected by stretch receptors in left atrium & causes release of ANP Inhibits aldosterone, promoting salt & water excretion to lower blood volume Promotes vasodilation

28. Factors Affecting Blood Flow

29. Vascular Resistance to Blood Flow Determines how much blood flows through a tissue or organ Vasodilation decreases resistance, increases blood flow Vasoconstriction does opposite

31. Physical Laws Describing Blood Flow Blood flows through vascular system when there is pressure difference (DP) at its two ends Flow rate is directly proportional to difference (DP = P1 - P2)

32. Physical Laws Describing Blood Flow Flow rate is inversely proportional to resistance Flow = DP/R Resistance is directly proportional to length of vessel (L) & viscosity of blood (?) Inversely proportional to 4th power of radius So diameter of vessel is very important for resistance Poiseuille's Law describes factors affecting blood flow Blood flow = DPr4(?) ?L(8)

34. Sympathoadrenal activation causes increased CO & resistance in periphery & viscera Blood flow to skeletal muscles is increased Because their arterioles dilate in response to Epi & their Symp fibers release ACh which also dilates their arterioles Thus blood is shunted away from visceral & skin to muscles Extrinsic Regulation of Blood Flow

35. Parasympathetic effects are vasodilative However, Parasymp only innervates digestive tract, genitalia, & salivary glands Thus Parasymp is not as important as Symp Angiotenin II & ADH (at high levels) cause general vasoconstriction of vascular smooth muscle Which increases resistance & BP Extrinsic Regulation of Blood Flow continued

36. Paracrine Regulation of Blood Flow Endothelium produces several paracrine regulators that promote relaxation: Nitric oxide (NO), bradykinin, prostacyclin 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 Endothelin 1 is vasoconstrictor produced by endothelium

37. Intrinsic Regulation of Blood Flow (Autoregulation) Maintains fairly constant blood flow despite BP variation 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

38. Metabolic control mechanism matches blood flow to local tissue needs Low O2 or pH or high CO2, adenosine, or K+ from high metabolism cause vasodilation which increases blood flow (= active hyperemia) Intrinsic Regulation of Blood Flow (Autoregulation) continued

39. Aerobic Requirements of the Heart Heart (& brain) must receive adequate blood supply at all times Heart is most aerobic tissue--each myocardial cell is within 10 m of capillary Contains lots of mitochondria & aerobic enzymes During systole coronary, vessels are occluded Heart gets around this by having lots of myoglobin Myoglobin is an 02 storage molecule that releases 02 to heart during systole

40. Regulation of Coronary Blood Flow Blood flow to heart is affected by Symp activity NE causes vasoconstriction; Epi causes vasodilation Dilation accompanying exercise is due mostly to intrinsic regulation

41. 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

44. Cerebral Circulation Gets about 15% of total resting CO Held constant (750ml/min) over varying conditions Because loss of consciousness occurs after few secs of interrupted flow Is not normally influenced by sympathetic activity

45. Cerebral Circulation Is regulated almost exclusively by intrinsic mechanisms When BP increases, cerebral arterioles constrict; when BP decreases, arterioles dilate (=myogenic regulation) Arterioles dilate & constrict in response to changes in C02 levels Arterioles are very sensitive to increases in local neural activity (=metabolic regulation) Areas of brain with high metabolic activity receive most blood

46. Cutaneous Blood Flow Skin serves as a heat exchanger for thermoregulation Skin blood flow is adjusted to keep deep-body at 37oC By arterial dilation or constriction & activity of arteriovenous anastomoses which control blood flow through surface capillaries Symp activity closes surface beds during cold & fight-or-flight, & opens them in heat & exercise

47. Blood Pressure

48. Blood Pressure (BP) Arterioles play role in blood distribution & control of BP Blood flow to capillaries & BP is controlled by aperture of arterioles Capillary BP is decreased because they are downstream of high resistance arterioles

49. Blood Pressure (BP) Capillary BP is also low because of large total cross-sectional area

50. Blood Pressure (BP) Is controlled mainly by HR, SV, & peripheral resistance An increase in any of these can result in increased BP Sympathoadrenal activity raises BP via arteriole vasoconstriction & by increased CO Kidney plays role in BP by regulating blood volume & thus stroke volume

51. Baroreceptor Reflex Is activated by changes in BP Which is detected by baroreceptors (stretch receptors) located in aortic arch & carotid sinuses Increase in BP causes walls of these regions to stretch, increasing frequency of APs Baroreceptors send APs to vasomotor & cardiac control centers in medulla Is most sensitive to decrease & sudden changes in BP

54. Atrial Stretch Receptors Are activated by increased venous return & act to reduce BP Stimulate reflex tachycardia (slow HR) Inhibit ADH release & promote secretion of ANP

55. Measurement of Blood Pressure Is via auscultation (to examine by listening) No sound is heard during laminar flow (normal, quiet, smooth blood flow) Korotkoff sounds can be heard when sphygmomanometer cuff pressure is greater than diastolic but lower than systolic pressure Cuff constricts artery creating turbulent flow & noise as blood passes constriction during systole & is blocked during diastole 1st Korotkoff sound is heard at pressure that blood is 1st able to pass thru cuff; last occurs when can no long hear systole because cuff pressure = diastolic pressure

56. Measurement of Blood Pressure continued Blood pressure cuff is inflated above systolic pressure, occluding artery As cuff pressure is lowered, blood flows only when systolic pressure is above cuff pressure, producing Korotkoff sounds Sounds are heard until cuff pressure equals diastolic pressure, causing sounds to disappear

57. Pulse Pressure Pulse pressure = (systolic pressure) � (diastolic pressure) Mean arterial pressure (MAP) represents average arterial pressure during cardiac cycle Has to be approximated because period of diastole is longer than period of systole MAP = diastolic pressure + 1/3 pulse pressure