Page 0: Page 1: Chapter 14 Cardiac Output, Blood Flow, and Blood Pressure 14-1 Page 2: Chapter 14 Outline Cardiac Output Blood & Body Fluid Volumes Factors Affecting Blood Flow Blood Pressure Hypertension Circulatory Shock 14-2 Page 3: LOGO Cardiac Output 14-3 Page 4: Cardiac Output (CO) Is volume of blood pumped/min by each ventricle Heart Rate (HR) = 70 beats/min Stroke volume (SV) = blood pumped/beat by each ventricle  Average is 70-80 ml/beat CO = SV x HR Total blood volume is about 5.5L 14-4 Page 5: 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)  Mechanisms that affect HR: chronotropic effect • Positive increases; negative decreases Autonomic innervation of SA node is main controller of HR  Symp & Parasymp nerve fibers modify rate of spontaneous depolarization 14-5 Page 6: Regulation of Cardiac Rate continued  NE & Epi stimulate opening of pacemaker HCN channels  This depolarizes SA faster, increasing HR Fig 14.1  ACh promotes opening of K+ channels  The resultant K+ outflow counters Na+ influx, slows depolarization & decreasing HR 14-6 Page 7: Regulation of Cardiac Rate continued Vagus nerve:  Decrease activity: increases heart rate  Increased activity: slows heart Cardiac control center of medulla coordinates activity of autonomic innervation Sympathetic endings in atria & ventricles can stimulate increased strength of contraction 14-7 Page 8: 14-8 Page 9: 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 14-9 Page 10: Regulation of Stroke Volume 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  SV is inversely proportional to TPR Ejection fraction is SV/ EDV (~80ml/130ml=62%)  Normally is 60%; useful clinical diagnostic tool 14-10 Page 11: 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 14-11 Fig 14.2 Page 12: Frank-Starling Law of the Heart continued  (a) is state of myocardial sarcomeres just before filling  Actins overlap, actinmyosin interactions are reduced & contraction would be weak  In (b, c & d) there is increasing interaction of actin & myosin allowing more force to be developed Fig 14.3 14-12 Page 13: At any given EDV, contraction depends upon level of sympathoadren al activity  NE & Epi produce an increase in HR & contraction (positive inotropic effect) • Due to increased Ca2+ in sarcomeres Fig 14.4 14-13 Page 14: Extrinsic Control of Contractility Parasympathetic stimulation  Negative chronotropic effect • Through innervation of the SA node and myocardial cell  Slower heart rate means increased EDV • Increases SV through Frank-Starling law Page 15: Fig 14.5 14-14 Page 16: 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 Fig 14.7 14-15 Page 17: 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 0Fig 14.6 10 mm Hg pressure 14-16 Page 18: LOGO Blood & Body Fluid Volumes 14-17 Page 19: 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 Fig 14.8 14-18 Page 20: 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) 14-19 Page 21: 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 14-20 Page 22: Overall Fluid Movement Is determined by net filtration pressure & forces opposing it (Starling forces)  Pc + P i (fluid out) - Pi + P p (fluid in) Pc = Hydrostatic pressure in capillary P i = Colloid osmotic pressure of interstitial fluid Pi = Hydrostatic pressure in interstitial fluid P p = Colloid osmotic pressure of blood plasma 14-21 Page 23: Fig 14.9 14-22 Page 24: 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 14-23 Page 25: 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 14-24 Page 26: 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 Fig 14.11 14-25 Page 27: 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 14-26 Page 28: Renin-Angiotension-Aldosterone System Decreased BP and flow (low blood volume) Kidney secreted Renin (enzyme)  Juxaglomerular apparatus Angiotensin I to AngiotensinII  By angiotensin-converting enzyme (ACE) Angio II causes a number of effects all aimed at increasing blood pressure: • Vasoconstriction, aldosterone secretion, thirst 14-27 Page 29: Angiotensin II  Fig 14.12 shows when & how Angio II is produced, & its effects 14-28 Page 30: 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 14-29 Page 31: LOGO Factors Affecting Blood Flow 14-30 Page 32: Vascular Resistance to Blood Flow Determines how much blood flows through a tissue or organ  Vasodilation decreases resistance, increases blood flow  Vasoconstriction does opposite 14-31 Page 33: 14-32 Page 34: 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) Fig 14.13 14-33 Page 35: 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) 14-34 Page 36: Fig 14.14. Relationship between blood flow, radius & resistance 14-35 Page 37: Extrinsic Regulation of Blood Flow 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 14-36 Page 38: Extrinsic Regulation of Blood Flow continued Parasympathetic effects are vasodilative  However, Parasymp only innervates digestive tract, genitalia, & salivary glands  Thus Parasymp is not as important as Symp Angiotensin II & ADH (at high levels) cause general vasoconstriction of vascular smooth muscle  Which increases resistance & BP 14-37 Page 39: 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 14-38 Page 40: 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 14-39 Page 41: Intrinsic Regulation of Blood Flow (Autoregulation) continued 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) 14-40 Page 42: 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 14-41 Page 43: 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 14-42 Page 44: Regulation of Blood Flow Through Skeleta Muscles At rest, flow through skeletal muscles is low because of tonic sympathetic activity Flow through muscles is decreased during contraction because vessels are constricted 14-43 Page 45: 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 14-44 Page 46: Fig 14.19 14-45 Page 47: Fig 14.20 14-46 Page 48: 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 14-47 Page 49: 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 14-48 Page 50: Fig 14.21 14-49 Page 51: 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-orflight, & opens them in heat & exercise Fig 14.22 14-50 Page 52: LOGO Blood Pressure 14-51 Page 53: 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 Fig 14.23 14-52 Page 54: Blood Pressure (BP) Capillary BP is also low because of large total crosssectional area Fig 14.24 14-53 Page 55: 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 14-54 Page 56: 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 14-55 Page 57: Fig 14.26 14-56 Page 58: Fig 14.27 14-57 Page 59: 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 14-58 Page 60: 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 14-59 Page 61: 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 Fig 14.29 14-60 Page 62: Fig 14.30 14-61 Page 63: 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 14-62 Page 64: LOGO Hypertension 14-63 Page 65: Hypertension Is blood pressure in excess of normal range for age & gender (> 140/90 mmHg) Afflicts about 20 % of adults Primary or essential hypertension is caused by complex & poorly understood processes Secondary hypertension is caused by known disease processes 14-64 Page 66: Essential Hypertension  Constitutes most of hypertensives  Increase in peripheral resistance is universal  CO & HR are elevated in many  Secretion of renin, Angio II, & aldosterone is variable  Sustained high stress (which increases Symp activity) & high salt intake act synergistically in development of hypertension  Prolonged high BP causes thickening of arterial walls, resulting in atherosclerosis  Kidneys appear to be unable to properly excrete Na+ and H20 14-65 Page 67: Dangers of Hypertension Patients are often asymptomatic until substantial vascular damage occurs  Contributes to atherosclerosis  Increases workload of the heart leading to ventricular hypertrophy & congestive heart failure  Often damages cerebral blood vessels leading to stroke  These are why it is called the "silent killer" 14-66 Page 68: Treatment of Hypertension Often includes lifestyle changes such as cessation of smoking, moderation in alcohol intake, weight reduction, exercise, reduced Na+ intake, increased K+ intake Drug treatments include diuretics to reduce fluid volume, beta-blockers to decrease HR, calcium blockers, ACE inhibitors to inhibit formation of Angio II, & Angio II-receptor blockers 14-67 Page 69: LOGO Circulatory Shock 14-68 Page 70: Circulatory Shock Occurs when there is inadequate blood flow to, &/or O2 usage by, tissues  Cardiovascular system undergoes compensatory changes  Sometimes shock becomes irreversible & death ensues 14-69 Page 71: Hypovolemic Shock Is circulatory shock caused by low blood volume  E.g. from hemorrhage, dehydration, or burns  Characterized by decreased CO & BP Compensatory responses include sympathoadrenal activation via baroreceptor reflex  Results in low BP, rapid pulse, cold clammy skin, low urine output 14-70 Page 72: Septic Shock Refers to dangerously low blood pressure resulting from sepsis (infection) Mortality rate is high (50-70%) Often occurs as a result of endotoxin release from bacteria  Endotoxin induces NO production causing vasodilation & resultant low BP  Effective treatment includes drugs that inhibit production of NO 14-71 Page 73: Other Causes of Circulatory Shock Severe allergic reaction can cause a rapid fall in BP called anaphylactic shock  Due to generalized release of histamine causing vasodilation Rapid fall in BP called neurogenic shock can result from decrease in Symp tone following spinal cord damage or anesthesia Cardiogenic shock is common following cardiac failure resulting from infarction that causes significant myocardial loss 14-72 Page 74: Congestive Heart Failure Occurs when CO is insufficient to maintain blood flow required by body Caused by MI (most common), congenital defects, hypertension, aortic valve stenosis, disturbances in electrolyte levels Compensatory responses are similar to those of hypovolemic shock Treated with digitalis, vasodilators, & diuretics 14-73 Page 75: