CARDIOVASCULAR PHYSIOLOGY ELECTRICAL CONDUCTION OF THE HEART

Transcription

1 CARDIOVASCULAR PHYSIOLOGY Check ut the Cardilgy_Flash_Cards fr a nice summary f ECG. Electrical Cnductin f the Heart The Cardiac Cycle Hemdynamics Mycardial Perfrmance Valvular Dysfunctin The Micrcirculatin Cardivascular Cntrl Mechanisms Shck and Hypertensin MYOCARDIUM DEPOLARIZATION: ELECTRICAL CONDUCTION OF THE HEART Phase 0: Initial upswing f actin ptential. Na + Channels pen until threshld is reached. Phase 1: The ptential may replarize slightly befre starting the plateau phase. Na + Channels are inactivated. Outward Rectifier K + Channels pen transiently, causing slight replarizatin. Membrane ptential remains near zer. Phase 2: Plateau Phase -- This stage is respnsible fr prlnging the cardiac actin ptential, making it lnger than a nerve actin ptential. Ca +2 Channels pen, t keep the cells deplarized. Phase 3: Replarizatin Ca +2 Channels clse. Delayed Rectifier K + Channels pen t effect nrmal replarizatin. Phase 4: Diastlic membrane ptential. Inward Rectifier K + Channels (different than the nes abve) are pen, t maintain resting ptential. They are pen at highly negative membrane ptentials (i.e. hyperplarizatin-activated). SA-NODE DEPOLARIZATION: It is similar t deplarizatin in the mycardium, except fr the fllwing differences: Deplarizatin results frm influx f Ca +2 rather than Na + There is n plateau phase (n Phase 1 and 2). Autmaticity: Hyperplarizatin-activated catin current is activated at lw ptentials, resulting in autmaticity f the SA-Nde. Epinephrine increases the rate f rise and acetylchline decreases the rate f rise f Phase-4 deplarizatin. REFRACTORY PERIOD: Cardiac muscle cells have prlnged refractry perids, t prevent tetany f cardiac muscle. AUTONOMIC REGULATION f HEARTBEAT: Acetylchline slws heart rate by increasing K + permeability. Nrepinephrine speeds heart rate by increasing the rate f rise f the cardiac actin ptential during phase 0. PROPAGATION f ACTION POTENTIAL: ATRIAL CONTRACTION: It takes abut 70 msec t get frm the SA-Nde > deplarize the atria > t the AV-Nde. AV-NODAL DELAY: There is a delay in deplarizatin f abut 90msec, nce the impulse reaches the AV-Nde. 1

2 The functin f this delay is t separate the cntractin f the atria (i.e. atrial systle) frm that f the ventricles (ventricular systle), s that mre bld has a chance t fill int the ventricles. The AV-Nde depends n slw-cnducting Ca +2 Channels fr deplarizatin, which helps t explain its slw rate f deplarizatin. A smaller cell-size als helps t explain the slw rate f cnductance. BUNDLE OF HIS BUNDLE-BRANCHES: Tw cntinuing branches f the Bundle f His. Left Bundle Branch: It deplarizes first. Deplarizatin ges frm the left side f the ventricular septum t the right side, accunting fr the Q-Wave. Right Bundle Branch: It deplarizes after the left side. PURKINJE SYSTEM: Very fast cnductin. VENTRICULAR MUSCLE As deplarizatin prceeds in the ventricles, it mves frm endcardium > epicardium. EKG LIMB LEADS: Deplarizatin ccurs tward the psitive side (the psitive sides are labelled t the right, and the respective negative sides are unlabeled). HEXAXIAL SYSTEM: The psitive end f each limb lead is as fllws: I: 0 II: +60 III: +120: In a nrmal ECG, Lead III shuld have a net-zer QRS-Cmplex, as it is perpendicular t avr. avr: -150: In a nrmal ECG, the avr lead shuld have a cmpletely negative QRS Cmplex. avl: -30 avf: +90 DIRECTION OF ECG DEFLECTION: A psitive deflectin n an ECG represents a deplarizatin that is traveling tward the psitive side f a particular lead. Maximal Psitive Deflectin: Occurs when deplarizatin vectr is in the exact same directin as the limb lead. ELECTROCARDIOGRAM: Zer net deflectin: Occurs when deplarizatin vectr is exactly perpendicular t limb lead. Maximal Negative Deflectin: Occurs when deplarizatin vectr is in the exact ppsite directin as the limb lead (i.e. in the directin f the negative end). P-WAVE: Atrial deplarizatin. P-Wave duratin is nrmally 80 msec. PR-INTERVAL: The distance frm the beginning f the P-Wave t the beginning f the Q-Wave. PR-Interval is the perid frm beginning f atrial deplarizatin t the beginning f ventricular deplarizatin. PR-Interval is nrmally msec. PR-SEGMENT: The distance frm the end f the P-Wave and the beginning f the Q-Wave. QRS-COMPLEX: Ventricular Deplarizatin. QRS Duratin is nrmally msec. Individual Cmpnents: Q-WAVE: Deplarizatin f the septum. On mst leads (except III and avr) the Q-Wave pints dwnward if it can be seen at all. Septum deplarizatin ges frm the left side f the septum t the right side. R-WAVE: Deplarizatin f the ventricles. Sharp upward turn. S-WAVE: Return f vlt-ptential t zer, because all the ventricular muscle has deplarized and is therefre nce again iselectric. Sharp dwnward turn back t iselectric pint. The S-Wave may g slightly negative befre return back t iselectric pint. QT-INTERVAL: Frm beginning f Q-Wave t end f T-Wave. QT-Interval is nrmally msec. This is the perid frm beginning f ventricular deplarizatin t the end f replarizatin. ST-SEGMENT: Shrt segment frm end f S-Wave t beginning f T-Wave. ST-INTERVAL: Frm end f S-Wave t end f T-Wave. RR-INTERVAL: Distance between QRS-Cmplexes, r the distance between heart beats in a nrmal sinus rhythm. 2

3 T-WAVE: Replarizatin f Ventricles. Atrial replarizatin masked by QRS-Cmplex. Replarizatin ccurs in the ppsite directin as deplarizatin, but the vectr still pints in the same directin because the change in vltage als has an ppsite sign. In the ventricles, the first tissue t deplarize is the last tissue t replarize. READING THE ECG: Vertical Directin: 10 mm = 2 big bxes = 1 mv deflectin. Hrizntal Directin: 1 mm = 40 msec. At standard speed, there are 25 mm, r 5 big bxes, in each secnd. Speeds: Standard Speed = 25 mm/sec Extra-Sensitivity Speed = 50 msec, at which pint all values abve must be dubled. PRECORDIAL LEADS: V1 thru V6 are placed t specific places n the chest, fr advanced ECG diagnstics. V1 is right-mst, near the SA-Nde, while V6 is leftmst, past the apex f the heart. MEAN ELECTRICAL AXIS OF THE HEART: Tw ways t graphically determine mean electrical axis: SHORT WAY: This is nly accurate when there is a net QRS-Deflectin f virtually zer (i.e. the R deflectin is equal and ppsite t the S deflectin). Determine the lead that has a net zer QRS-Deflectin. On the hexaxial system, the mean electrical axis pints in the directin that is perpendicular t that lead. LONG WAY: This is lnger but mre accurate. Cnsider any tw f the six hexaxial leads. Determine again the Net QRS-Deflectin fr each lead. Plt that deflectin alng the apprpriate axis n a hexaxial chart. Draw a dtted line perpendicular t each f the abve plts, and extend the tw lines until the intersect each ther. The Mean Electrical Axis is the vectr that pints frm the center t the intersectin f thse tw lines. LAB: Different physilgical effects n the mean electrical axis: INSPIRATION: The diaphragm mves dwn > It pulls the apex f the heart tward the right (i.e. in a mre vertical directin) > the mean electrical axis is mre psitive (+ mre degrees). FORCED EXPIRATION: The exact ppsite f abve. The apex f the heart gets pushed upward and tward the left hrizntal axis > the mean electrical axis is less psitive r even negative. PREGNANCY: The mean electrical axis wuld deviate t the left, within nrmal limits. The physical presence f the fetus wuld push up the diaphragm > heart leans tward left. LEFT VENTRICULAR HYPERTROPHY: Mean axis deviatin tward the left. Pulmnary Valve Stensis: If we assume that it leads t Right Ventricular Hypertrphy > Then we get (ptentially severe) right axis deviatin. INFANCY: Right Axis Deviatin, because the infant's right ventricle and left ventricle musculature are abut the same size at birth. Left ventricle becmes larger within a cuple mnths. NORMAL MEAN AXIS: Anywhere between -30 and Anything negative f -30 is left axis deviatin, as ccurs frm left ventricular hypertrphy. Anything psitive f +110 is right axis deviatin, as ccurs frm right ventricular hypertrphy. ECG ABNORMALITIES: SINUS BRADYCARDIA: A heart rate slwer than 60 SA-Ndal deplarizatins per minute. "Sinus" indicates that the cardiac impulse is riginating frm the SA-Nde as nrmal. SINUS TACHYCARDIA: Heart rate faster than 100 bpm, riginating as nrmal frm the SA-Nde. Tachycardia generally means yu'll see a shrter RR-Interval (i.e. faster heart rate). SINUS ARREST: N SA-Nde deplarizatin. 3

4 This can be artificially induced by cartid massage, which results in verstimulatin f the Vagus > SA-Nde hyperplarized. ATRIAL PAROXYSMAL TACHYCARDIA: Faster heart rate resulting frm an ectpic pacemaker in the atrial muscle. In the example the P-Wave pints dwnward because the atrial deplarizatin starts in the LA, because that is where the tissue is leaky. BUNDLE-BRANCH BLOCKS: There is sme cnductin blck in the Bundle f His (Left r Right Bundle branches), with results as belw: 1 BLOCK: Partial blck. The PR-Interval is lnger than nrmal because it takes lnger t cnduct the impulse frm SA-Nde t AV-Nde. 2 BLOCK: A QRS-Cmplex ccurs nly after every ther P-Wave. In ther wrds, it takes tw P-Waves t sufficiently excite the AV-Nde t cnduct the impulse t the ventricles. 3 BLOCK: There is n tempral relatinship between the P-Wave and QRS-Cmplex. Atrial and ventricular deplarizatins are being cntrlled by their wn independent pacemakers (the SA-Nde and AV-Nde respectively). AV-NODAL TACHYCARDIA: Tachycardia, plus the P-Wave is insignificant r absent. This is tachycardia, where the impulse riginates frm the AV-Nde. The inherent pacemaker f the AV-Nde is faster than the SA-Nde. PREMATURE VENTRICULAR CONTRACTION (PVC): A premature QRS-Cmplex, r ne that ccurs withut being preceded by a P-Wave. That means that the P-Wave didn't start the impulse, but it started smewhere else. Ectpic Pacemaker: With PVC, the impulse riginates in the ventricular muscle itself, due t leaky membranes in the muscle. VENTRICULAR FIBRILLATION: Waves f deplarizatin traveling in multiple directins all ver the ventricular muscle. The pacemaker activity is lst. ATRIAL FIBRILLATION: Fibrillatin in the atria is nt serius in children, but it is serius in ld peple. That's because in ld peple, atrial systle cntributes a greater relative bld vlume t cardiac utput than in children. CLINICAL LECTURE: WOLF-PARKINSON-WHITE SYNDROME Nrmally, the AV-Nde is the nly pathway fr cnductin f the impulse frm the atria t the ventricles. Bachman's Bundle: Nrmally cnducts the impulse frm Right Atrium t Left Atrium during atrial systle. Mderatr Band: Nrmally cnducts the impulse frm the right ventricular septal wall t the right free wall during ventricular systle. Lupus Erythematsus: Rare cnditin assciated with pediatric bradycardia. Usually pediatric heart prblems result in Tachycardia -- nt bradycardia. PEDIATRIC TACHYCARDIAS: They are divided int tw types Supraventricular Tachycardia (SVT): One where the prblem riginates smewhere in the AV-System. Ventricular Tachycardia (VT): Prblem riginates in the ventricular system. Wlf-Parkinsn-White Syndrme: Extra cnductive tissue in the mycardium, creating an accessry pathway fr cnductin frm atria t ventricles. This accessry pathway ultimately results in a Reentry Tachycardia, r a cnductin lp between the nrmal and accessry pathways. The Wlf-Parkinsn-White ECG: Shrter PR-Interval due t rapid cnductin f signal t ventricles thrugh accessry pathway. This is the ECG when the patient is healthy and n prblems are ging n. The P-Wave and the QRS-Cmplex are scrunched tgether, creating the appearance f a delta-wave (hump right befre QRS), and a lnger verall QRS Cmplex. Reentry Tachycardia: Yu get it frm a unidirectinal blck in ne pathway, cupled with slwed cnductin f an alternative pathway. This results in cntinuus impulse cnductin, r circus dysrhythmia. With WPW, the accessry pathway can get blcked because it hasn't had the time t replarize, then the nrmal pathway prvides a mean fr retrgrade cnductin f deplarizatin. This results in a cnductin lp and severe tachycardia. TREATMENT: Slw dwn the cnductin thrugh ne pathway r the ther. Use Ca +2 -Channel Blckers (such as Verapamil) Use Digxin t increase AV-Ndal sensitivity t ACh. Use beta-blckers t blck the nrmal NrE sympathetic receptrs n the AV-Nde and cardiac muscle. 4

5 In severe cases, surgically remve the cnductive tissue frm the mycardium. THE CARDIAC CYCLE VENTRICULAR DIASTOLE: ISOVOLUMIC RELAXATION: The very beginning f diastle, right after the artic valve clses, during which bth valves are clsed. The ventricular muscle is relaxing as ventricular pressure rapidly decreases. Vlume remains cnstant. THREE PHASES OF VENTRICULAR FILLING: RAPID VENTRICULAR FILLING: The Mitral Valve pens, when ventricular pressure falls belw atrial pressure. Bld rushes int ventricle, very quickly initially. THIRD HEART SOUND (S3): It is turbulent bld flwing past the ventricular wall during early diastle. It is indicative f pathlgy. SLOW VENTRICULAR FILLING: The later perid f diastle. The majrity f bld has already entered the ventricles. TOP-OFF PHASE: The bld cntributed t ventricles during atrial systle. Diastlic Events Assciated with the Atria: V-Wave: Small increase in atrial pressure assciated with the fact that the mitral valve is clsed at the very beginning f diastle. Y-Descent: Descent f the V-Wave. Decrease in atrial pressure ccurring when the mitral valve pens, right after ventricular isvlumic relaxatin. A-Wave: Small rise in atrial pressure, ccurring right befre systle, assciated with Atrial Systle and cntrxn f atrial muscle. FOURTH HEART SOUND (S4): Vibratin f mitral valve leaflets during atrial systle, i.e. during the tpff phase f ventricular filling. This ccurs cncurrent with the A-Wave and is indicative f pathlgy. Atrial Fibrillatin: There is an age difference in the seriusness f this. Again, atrial fibrillatin isn't a cncern with yung peple but it is with ld peple. YOUNG: Atrial systle cntributes abut 20mL t strke vlume OLD: Atrial systle cntributes abut 40mL t strke vlume. An Increased heart rate makes the atrial cntributin t strke vlume mre significant. Shrter time fr ventricular filling > The tp-ff phase cntributes mre relative vlume t ventricles. VENTRICULAR SYSTOLE: QRS-Cmplex ccurs and ventricles start cntracting. FIRST HEART SOUND (S1): The Mitral Valve Clses, as ventricular pressure exceeds atrial pressure. ISOVOLUMIC CONTRACTION: Perid f cntractin during which bth valves are clsed Pressure is increasing. Vlume is cnstant. Systlic Events Assciated with the Atria: C-WAVE: Small increase in atrial pressure. Occurs during isvlumic cntractin, as the ventricle pushes the mitral valve a little upward tward the atrium. X-DESCENT: The decrease in the C-Wave, due t the change f shape f the ventricle frm prlate spherid (ftball-like) t spherid. This makes the mitral valve mve dwn and the atrial pressure return t nrmal. Artic Valve Opens, as ventricular pressure exceeds artic pressure. Ventricle must achieve systlic arterial pressure in rder t pen the Artic valve, s it reaches pressures arund 120 mm Hg. Ventricular Ejectin: 70% f bld is ejected in the first third f systle. SECOND HEART SOUND (S2): The artic valve clses, as ventricular pressure falls belw artic pressure. DICROTIC (AORTIC) NOTCH: When the Artic Valve clses, there is a temprary retrgrade flw f bld against the Artic valve cusps. This causes an acute decrease in Artic pressure at the very beginning f diastle. Tw Things act in cncert t make the Artic valve clse: The left ventricle relaxes s left ventricular pressure decreases. 5

6 The retrgrade bld flw against the leaflets actually aids in the clsure f the valve. HEART SOUNDS: Left Side -vs- Right Side: FIRST HEART SOUND (S1): The mitral valve (left side) clses befre the tricuspid valve (right side), because the deplarizatin begins n the left side f the septum. On the ther hand, the Artic Valve (left side) pens a little after the Pulmnary Valve (right side), because there is s much higher vlume in the left side, hence mre pressure has t build up befre valve will pen. SPLIT SECOND HEART SOUND: During inspiratin, Yu shuld be able t hear the pulmnic and artic valves clse separately during the secnd heart sund (i.e. a "split" sund). Pulmnic Stensis: In this case the pulmnic valve is nt pening well > Wide Splitting during inspiratin. Artic Stensis: Causes paradxical splitting -- i.e. splitting ccurs during expiratin instead f during inspiratin. HEMODYNAMICS NORMAL RANGE OF VALUES P-Wave QRS-Wave P-R Interval S-T Interval Q-T Interval ~ 80 msec msec msec msec msec Mean Electrical Axis -30 t +110 End Diastlic Vlume (LVEDV) End Systlic Vlume (LVESV) Strke Vlume (SV) ml ml ml Ejectin Fractin Cardiac Output (CO) L / min Cardiac Index L / min / m 2 Systlic Pressure Diastlic Pressure Systemic Resistance (TPR) Pulmnary Bld Distributin Heart Bld Distributin Systemic Arterial Bld Distributin Arterilar Bld Distributin Venus Bld Distributin mm Hg mm Hg 0.9 PRU, r mm Hg / ml / sec ~ 10% ttal; 500 ml ~ 10% ttal; 500 ml ~ 10% ttal; 500 ml ~ 5% ttal; 250 ml ~ 65% ttal; 3250 ml 6

7 Capillary Hydrstatic Pressure, P c Capillary Onctic Pressure, PI p Interstitial Hydrstatic Pressure, P i Interstitial Onctic Pressure, PI i Arterial Cmpliance Venus Cmpliance ~ 30 mm Hg ~ 25 mm Hg ~ 0 mm Hg 1-10 mm Hg 1 ml / mm Hg 20 ml / mm Hg STROKE VOLUME = (END DIASTOLIC VOLUME) - (END SYSTOLIC VOLUME) Cardiac Index is Cardiac Output nrmalized fr bdy mass. CARDIAC OUTPUT = (STROKE VOLUME) x (HEART RATE) PULSE PRESSURE = (SYSTOLIC PRESSURE) - (DIASTOLIC PRESSURE) MEAN ARTERIAL PRESSURE = (CO) x (TPR) = (HR) x (SV) x (TPR) PERIPHERAL RESISTANCE UNITS (PRU): Units f mm Hg / ml / sec. Or, it is TPR as abve, where CO is expressed in ml/sec. RESISTANCE alpha VISCOSITY Fr the lungs, this resistance is called Pulmnary Vascular Resistance, and the flw is equal t Cardiac Output. General Trends in Circulatin: Pressure drp is greatest at the level f the arteriles. Velcity f bld is slwest at the capillaries, because they have the largest ttal crss-sectinal area, given the number f capillaries. Turbulence: The higher the velcity f bld flw, the greater the likelihd f turbulence. Turbulence is mst likely in large arteries. Never in capillaries and rarely in venus system. Arterial Elasticity (The Windkessel Effect): Arterial Elasticity accunts fr a smaller pulse pressure. It relieves a little pressure during systle, since it can give a little. It maintains flw during diastle, since it can flex back. Thus, athersclersis > Larger Pulse Pressure. THE BASIS OF STEADY BLOOD FLOW: Systle -vs- Diastle Systle: Mre bld is pumped int the arterial tree then flws ut f the arterial tree, s arterial pressure rises. Hence vlume in arterial tree ges up > pressure in arterial tree ges up t systlic pressure. During systle, abut half f the bld is stred in the arterial tree, and the ther half is pushed int the capillary beds. Diastle: Bld cntinues t leave the arterial system and n new bld enters it, s bld pressure ges back dwn. During Diastle, mre arterial bld flws int the capillary beds, prviding capillaries with cntinuus bld flw whether in systle r diastle. MEASURING BLOOD PRESSURE / SPHYGMOMANOMETER: 7

8 SYSTOLIC PRESSURE: The first sund yu hear -- a rush f bld flwing thrugh the squeezed artery. This happens the instant that the cuff pressure is reduced enugh t let arterial bld squirt thrugh during systle. DIASTOLIC PRESSURE: The last sund yu hear -- bld is n lnger stpped by the cuff-pressure during diastle. Phases: Phase I (snapping): Phase II (murmur): In hypertensive peple, an auscultatry gap can ccur during Phase II. Phase III( thumping): Phase IV (muffling): The beginning f this muffling is smetimes taken as the high end f diastle. Sme peple think the muffling sund is a better indicatr f diastlic pressure fr children. Estimatins: SYSTOLIC PRESSURE is underestimated by auscultatin -- yu can't hear the sund "quick enugh" t recrd the measurement. DIASTOLIC PRESSURE is verestimated by auscultatin. Thus PULSE PRESSURE can be underestimated by auscultatin by a significant amunt. FLOW, VISCOSITY, TURBULENCE, RESISTANCE: TURBULENCE: Turbulence is directly related t velcity f fluid. The higher the velcity, the mre likely there is t be turbulence. Reynld's Equatin tells us the critical velcity at which turbulence will ccur. We can derive three relatinships frm that equatin: Turbulence alpha Flw: The higher the flw, the higher the likelihd f turbulence. Turbulence alpha (1 / viscsity): The lwer the viscsity, the higher the likelihd f turbulence. Turbulence alpha (1 / diameter): The narrwer the radius f the vessel, the higher the likelihd f turbulence. Turbulence is indicative f a larger pressure drp (larger DeltaP) acrss a regin f vessel. Thus turbulence ccurs when there is an athersclertic plaque. VISCOSITY: Relatin between viscsity and turbulence: Viscsity f bld is mst clsely related t hematcrit. 20% f bld viscsity if frm plasma; 80% is frm bld cells. ANEMIA: Lwer hematcrit > Lwer viscsity f bld > Higher bld flw > Higher likelihd f turbulence. FLOW: Relatin between flw and radius = flw is inversely prprtinal t r 4. RESISTANCE: The resistance t any rgan is greater than the sum f all resistances! That's true because the vessels are wired in parallel, and the sum f resistances in parallel is less than its individual parts. Systemic Resistance (TPR) is much greater than Pulmnary Resistance. Pulmnary Resistance = Delta Pulmnary Pressures / CO. BRUIT: Turbulent flw is detected as a bruit which can be heard by the stethscpe. Inncent Ejectin Murmur: Children can have high velcity f bld flw withut there being any pathlgy. Bruits are nt uncmmn. Bruits with Anemia: Anemic patients can als have inncent bruits, fr tw reasns: Lwer hematcrit > lwer bld viscsity > higher likelihd f turbulence. Anemics tend t cmpensate their lw hematcrit with a higher cardiac utput. Athersclertic Plaque: Turbulence can be heard dwnstream frm the plaque. Upstream frm Plaque: Greater resistance > a strng pulse pressure. Dwnstream frm Plaque: A bruit can be heard. STANDING BLOOD PRESSURE: Mean Arterial Pressure ges dwn when standing, because f lwer venus return. Stand up > Venus Pressure in feet ges up > capillary hydrstatic pressure ges up > fluid flws ut f arterial tree and int tissues > venus pling in the feet > venus return decreases > CO decreases > lwer MABP. Venus pressure ges up in feet because f gravity -- DeltaP = gh 8

9 Skeletal Muscle Pump: Tnic cntractin f leg muscles while standing aids venus return, because the veins have valves, s bld is squeezed in nly ne directin. Thus prlnged standing can lead t incmpetent valves in the veins in the legs. BLOOD PRESSURE AND THE RESPIRATORY CYCLE: INSPIRATION: Systemic bld pressure ges dwn and pulmnary bld pressure ges up. The Diaphragm mving dwn has tw effects: It increases the vlume f thracic airspace and s it decreases intrathracic pressure. Als the abdminal space becmes smaller, s it increases intra-abdminal pressure. The cmbinatin f abve tw effects results in an increased pressure gradient fr venus return frm the IVC > increased venus return > Mre bld t right atrium and mre bld t pulmnary circulatin > less respective bld in left heart and less CO. Thus verall result is the fllwing: Lwer systemic pressure. Higher pulmnary pressure. Larger Bld Vlume in pulmnary circulatin. The change in MABP frm inspiratin nrmally des nt exceed 10 mm Hg. EXPIRATION: Has the exact ppsite effect. Pulmnary pressure decreases. Systemic pressure increases. CENTRAL VENOUS PRESSURE: The pressure ging int the right atrium. Anything that decreases venus cmpliance (i.e. sympathetic tne) will increase venus return > Higher CVP. ESTIMATING CENTRAL VENOUS PRESSURE: Yu estimate in cm f water. It is apprximately equal t the distance frm the end f the distended part (which yu can see) t the sternal angle, plus 5, then cnvert it int mm Hg. PRESSURES IN PERIPHERY -vs- AORTA: Mean Arterial Pressure is slightly higher in the Arta than in, fr example, the radial artery. But, Pulse Pressure is greater in the periphery, i.e. the systlic is higher and the diastlic is lwer. This effect in the periphery is due t cnstructive interference f reflected waves. COMPLIANCE: The degree t which a pressure change leads t a crrespnding change in vlume. Or, Cmpliance = DeltaV / DeltaP, r the slpe f a pressure-vlume curve. VENOUS COMPLIANCE is abut twenty times mre than arterial cmpliance, therefre veins can hld a larger vlume f fluid at lwer pressure. Arterial Cmpliance is abut 1 ml / mm Hg Venus Cmpliance is abut 20 ml / mm Hg EFFECTS OF COMPLIANCE n Bld Pressure: Higher Venus Cmpliance > higher capacitance in veins > less venus return > lwer CVP. Lwer Venus Cmpliance (sympathetic influence) > lwer capacitance veins > mre venus return via the ne-way valves > higher CVP. Lwer Arterial Cmpliance results in a higher pulse pressure. AGE: Arteries in ld peple have lwer cmpliance. Thus ld peple have higher pulse pressures. Pressure-Vlume Curve: The analysis f ld -vs- yung can be dne n the P/V curve. The slpe f the curve is cmpliance. Pressure is n the X-Axis. Vlume is n the Y-Axis. Is yu plt systlic and diastlic pressure, and lk at the crrespnding Y-Values, yu can calculate the fllwing: The difference n the Y-axis (i.e. the vlumes crrespnding t systlic and diastlic pressures) is strke vlume. 9

10 The difference n the X-axis is pulse pressure. MODULATION OF MEAN ARTERIAL PRESSURE: Under a lt f circumstances, it desn't change, even when strke vlume and/r pulse pressures d change. EFFECT OF STROKE VOLUME: All ther factrs held cnstant, a high strke vlume results in a higher pulse pressure, i.e. higher systlic and lwer diastlic, but MABP remains cnstant. PULSE PRESSURE IS USUALLY DIRECTLY RELATED TO STROKE VOLUME EFFECT OF EXERCISE: Increased CO and Strke Vlume Cmpensatry lwer vascular resistance (TPR) Once again MABP desn't change (within limits). HIGH SYSTOLIC PRESSURE: Tends t ccur with higher strke vlume. The mre fluid yu pump in ne beat, the higher the systlic pressure. HIGHER DIASTOLIC PRESSURE: CORRELATES WITH HIGH TPR. General Effects f Autnmic Cntrl n Heart: MYOCARDIAL PERFORMANCE SYMPATHETICS: Psitive chrntrpic effect -- faster heart rate. Psitive intrpic effect -- greater cntractility fr the same fiber length. PARASYMPATHETICS: Negative chrntrpic effect, but n intrpic effect. PRELOAD: The diastlic filling pressure, r end-diastlic vlume. AFTERLOAD: Ventricular systlic pressure, which is equal t arterial systlic pressure under nrmal circumstances. LAPLACE'S LAW: The stress n the ventricular wall is prprtinal t the Ventricular Pressure x Ventricular Radius, where the size f the ventricle is determined by stretching, i.e. by ventricular vlume. STARLING'S LAW OF THE HEART: Within limits, increases in end-diastlic vlume result in a crrespnding increase in strke vlume. Mst simplified, within limits, the vlume that cmes int the heart ges back ut. MECHANISM: Increased Filling Vlume > Stretch Ventricular Muscle > Augmented ventricular fiber length > greater intrpic state > faster velcity f ejectin > Greater Cardiac Output. Increased fiber length results in mre frceful cntractin, within limits. Optimal muscle fiber length = 2.2 micrn. Heart nrmally wrks slightly belw this level t give rm fr ptimal filling. PRESSURE-VOLUME LOOP: P/V graph, with bth diastlic and systlic lines pltted n it. Yu use this graph t plt the pressure and vlume at all pints in the cardiac cycle. END-SYSTOLIC CURVE: The upper limit t the lp. END-DIASTOLIC CURVE: The lwer limit t the lp. CARDIAC CYCLE in LOOP: DIASTOLE: ISOVOLUMIC RELAXATION: Vlume is cnstant while pressure ges straight dwn. VENTRICULAR FILLING: Pressure remains cnstant while vlume increases. SYSTOLE: ISOVOLUMIC CONTRACTION: Vlume cnstant while pressure ges straight up. 10

11 EJECTION: Pressure cntinues t increase as bld is ejected frm the ventricle. The endpressure at this pint is systlic arterial pressure. The pressure cntinues t rise during systle because pressure is rising in the arterial netwrk. Yu are putting mre bld int the arterial tree then is being put ut n the ther side. Ventricle must match that rise in pressure t frce bld ut. AORTIC VALVE CLOSES: At the end f systle, the ventricular pressure (i.e. fiber length) decreases t the pint that the artic valve can't stay pen, s it clses. STROKE WORK: The area f the Pressure-Vlume Lp. Mathematically, that means: Strke Wrk = (Strke Vlume) x (Mean Arterial Pressure) STROKE WORK is equivalent t strke vlume, but it is nrmalized fr differences in bld pressure. Thus it is a gd indicatr f heart perfrmance. Because we have nrmalized fr bld pressure, a shift in the curve fr strke wrk means that there must be an increase in the intrpic state. VENTRICULAR FUNCTION CURVE: A cmparisn f End-Diastlic Vlume (r Pressure r Fiber Length) and Strke Vlume (r Strke Wrk). The curve is essentially a line that levels ff at high values. It is a way f expressing Starling's Law. If yu plt Strke Wrk -vs- LVEDV, yu will get the same curve fr the same intrpic state, regardless f bld pressure. S using Strke Wrk nrmalizes fr bld pressure, and it makes the curve represent the intrpic state. EFFECT OF PRELOAD ON STROKE-WORK: Standing at Rest: The least strke wrk is perfrmed. SINE > Prelad (venus return) increases > Fiber-length increases >------> Higher Strke Wrk. PRONE, with LEGS RISEN: Even mre prnunced effect as abve > higher strke wrk. EFFECT OF AFTERLOAD ON STROKE VOLUME: A higher afterlad > Higher systlic pressure must be develped > Higher end-systlic vlume t achieve that pressure, but the end-diastlic vlume remains the same > lwer strke vlume. AUTOREGULATION OF AFTERLOAD: Due t hetermetric autregulatin, within limits, strke vlume will be maintained even in face f a higher bld pressure, but it takes a few beats fr the mechanism t kick in. High afterlad > Lwer strke vlume > Since pulmnary arterial pressure hasn't changed, the right heart cntinues t pump the same strke vlume as befre > Pulmnary bld vlume increases > Higher venus return back t left atrium > Higher prelad > Higher fiber length + velcity f ejectin > > Strke vlume returns t nrmal But a new pressure-vlume curve is carved ut n the P/V-Lp. Strke-wrk verall has increased. In cmpensating fr the higher bld pressure, we must use sme f ur Starling Reserve -- the extra capacity in the heart t d strke wrk, strictly because f the Starling mechanism. TOTAL RESERVE: The ttal stred capacity the heart has t d extra strke wrk. It is equal t Starling Reserve + Intrpic Reserve + Heart-Rate Reserve. STARLING RESERVE: The extent t which we can increase Cardiac Output simple by increasing filling, at the same intrpic state. INOTROPIC RESERVE HEART-RATE RESERVE INOTROPIC STATE: It's the cntractile frce in the muscle, at any particular fiber-length. That is the same as the Ca +2 cncentratin in the sarcmeres. It increases strke vlume, DUH?? 11

12 HEART-RATE AND STROKE VOLUME: Heart rate extremes lead t lwer strke vlume. Bradycardia: Heart-rate slwer than 40. Cardiac Output ges way dwn because the strke vlume can't increase enugh t cmpensate fr the lwer heart-rate. Yu've reached the maximum f the heart's intrpic state. Tachycardia: Heart-rate faster than 180. Cardiac Output ges way dwn because there is n lnger enugh time between beats fr sufficient ventricular filling, i.e. the shrt diastlic time cuts int the "Fast-Filling Phase" f diastle. VALVULAR DYSFUNCTION MITRAL INSUFFICIENCY: Insufficiency means the valve can't stay cmpletely clsed, s it is leaky. Mitral Insufficiency causes fluid t reflux int the Left Atrium with each systle, leading t a chrnically high end-diastlic vlume > leftventricular hypertrphy. Hlsystlic Murmur can be heard thrughut systle, as turbulent bld flws thrugh mitral valve. Third Heart Sund can be heard during diastle, as there is a large excess f atrial bld > turbulent flw during ventricular filling. Large V-Wave is seen: Higher atrial pressure prduced during diastle, because there is higher atrial vlume. MITRAL STENOSIS: Leads t lwer filling f the left atrium, as the system backs up. This leads t verlad f bld in the pulmnary system. High Pulmnary Arterial Pressure frm backup f bld. Pulmnary Edema is a likely cmplicatin that can result frm the pulmnary hypertensin. Right Ventricular Hypertrphy als cmmnly cmes frm high Pulmnary hypertensin. Heart Sunds: Pre-Systlic Crescend Murmur is diagnstic f mitral stensis. The murmur results frm large increases f pressure during atrial systle, because f the mitral stensis. Diastlic (S3) Decrescend Murmur is als heard, as there is a large pressure difference between atrium and ventricle during diastle. That pressure difference then becmes smaller (i.e. quieter) as the ventricle fills and the atrium empties. AORTIC INSUFFICIENCY: Regurgitatin back int left-ventricle, n each systle, leads t severe left-ventricular hypertrphy (when the insufficiency is severe). Dangerusly Large Pulse Pressure results frm high systlic pressure (due t cmpensatry mechanism / intrpic state), and markedly decreased diastlic pressure (due t lw strke vlume). High LVEDV > Left-Ventricular Hypertrphy which can be severe. Heart Sunds: Lud Hl-Diastlic Decrescend Murmur. AORTIC STENOSIS: Very cmmn in ld peple. Severe Left Ventricular Hypertrphy. The stensis results in left ventricular pressure being a lt higher then artic pressure. HEART SOUND: Diamnd-Shaped Pansystlic Murmur -- i.e. diamnd-shape = crescend then decrescend. THE RIGHT HEART: Tricuspid and Pulmnic Valve prblems are similar t thse fund in the left heart. MEASUREMENT OF CARDIAC OUTPUT (Last few pages f handut): Direct Fick Methd: Yu calculate bld flw thrugh the lungs (rate f O 2 uptake) t determine the pulmnary flw. Then yu assume that pulmnary bld flw is equal t systemic bld flw (i.e. CO). This assumptin is true as lng as there are n intracardiac shunts. Indirect Fick (Thermal Dilutin) Methd: Calculatin bld flw essentially by measuring the time that it takes fr the flw f bld t neutralize a temperature difference between injected saline and bdy temp. 12

13 THE MICROCIRCULATION CAPILLARY FILTRATION AND RESORPTION: STARLING PRINCIPLE FOR CAPILLARY EXCHANGE: Filtratin: Bld leaving capillary and entering rgan. Net flw utward. P c, capillary hydrstatic pressure cntributes t this utflw. PI i, interstitial nctic pressure cntributes t this utflw. It is the nctic (smtic) pressure created by insluble prteins in the interstitial space. Absrptin: Bld leaving rgan and entering capillary. Net flw int capillary. P i, interstitial hydrstatic pressure, des nt cntribute t absrptin under nrmal circumstances. It is ~ 0. PI p, capillary nctic pressure, is the primary cntributr t resrptin. This is the smtic pressure created by insluble prteins in the bld. sigma, REFLECTION COEFFICIENT: It is equal t the percentage f prteins that are impermeable t the capillary membrane, i.e. a value between 0 and 1. sigma = 1: Prteins are ttally impermeable; all f them are "reflected" ff the membrane, thus nctic pressure has the greatest influence pssible n net filtratin. sigma = 0: Prteins are cmpletely permeable, hence n prteins are impermeable and nctic pressures becme zer. Lw reflectin cefficient affects resrptin but nt s much filtratin, since the capillary nctic pressure is the nly significant frce fr resrptin. RESULT: Edema. Lymphatics: Under nrmal circumstances, filtratin is greater than absrptin. Thus mre bld is being depsited in rgan systems than is being taken up. The difference is put back int the bld thrugh the lymphatic system. The entire bld circulatin is turned arund thrugh the lymphatic system every 24 hrs. Capillary Hydrstatic Pressure: R a = arterial resistance is nrmally much larger than venus resistance. We can usually safely ignre venus resistance in the calculatin. P v = venus pressure P a = mean arterial pressure INFLUENCES ON FILTRATION: ARTERIOLAR RESISTANCE: Nte that lcal(arterilar) changes t vascular tne have an exact ppsite effect as systemic (large artery) changes. All things cnstant, increased arterial resistance > lwer capillary hydrstatic pressure + lwer filtratin Vascnstrictin r dilatin at the level f the arteriles des nt affect MABP. Arterilar Vascnstrictin > > lwer filtratin rate. Arterilar Vasdilatin >------> higher filtratin rate. VENOUS PRESSURE: Increased Venus Pressure > Higher Capillary Hydrstatic Pressure > Increased Net Filtratin, because f the hydrstatic pressure equatin: The capillary pressure must increase in rder t achieve filtratin in face f the increased venus pressure. ONCOTIC PRESSURE: Negative nitrgen balance r prtein malnutritin (kwashirkr) will lead t lw plasma albumin > lw plasma nctic pressure > lw r n resrptin, which means high net rate f filtratin > edema, ascites CAPILLARY PERMEABILITY: Three types f capillaries, each having different levels f permeability: Cntinuus: Tight Junctins, as in brain, thymus, retina. Fenestrated: Little diaphragms where diffusin can take place, having smewhat higher permeability. GI-Tract. 13

14 Discntinuus: Liver sinusids, cmplete discntinuities in the system. Endthelial Cells: When endthelial cells cntract, the spaces between them increase > higher capillary permeability. Mast Cell Degranulatin leads t release f Histamine and Platelet-Activating Factr (PAF). This makes the endthelial cell release Calcium frm the SR > actin-mysin cntractin f endthelial cell makes the cell change shape > mre spaces between the cells. Anaphylactic Shck: High capillary permeability leads t lw bld pressure. We can't just give them fluids t increase bld vlume, because the fluids leak right ut again. EDEMA: It can ccur frm a lt f surces, such as n resrptin. Cnsequences f edema: Impair Exchange f Metablites: It leads t bigger spaces (lnger distance) between capillaries and the tissues > diffusin becmes impssible. THE EDEMA POSITIVE-FEEDBACK CYCLE: Edema can cmpress venules > higher venus return > higher CVP > higher hydrstatic pressure and filtratin rate > even mre edema. LYMPHATIC BLOCKAGE: If yu blck lymphatics, then interstitial fluid alng with interstitial prteins will rise > increase interstitial nctic pressure > mre filtratin > massive edema. VASCULAR SMOOTH MUSCLE: Anything that increases intracellular Ca +2 cncentratin will increase cntractility f vascular muscle. VASCULAR CONTRACTION: Mechanism f Cntractin, briefly: Calcium binds t Calmdulin The Ca +2 -Calmdulin Cmplex then binds t Mysin Light-Chain Kinase This results in mysin being free t interact with actin. Vascular Tne: The verall rate f crss bridging is much slwer than in vascular smth muscle. There is always a baseline level f activity = vascular tne. Nrepinephrine will cause vascular cntractin by increasing Ca +2 in smth muscle, via three pathways: NrE can directly pen Ca +2 -Channels NrE can bind t alpha1-receptrs t active the alpha-adrenergic Pathway (DAG/IP 3 ) > higher intracellular Ca +2 Vltage-Gated Ca +2 Channels can further pen, in respnse t the abve tw. VASCULAR RELAXATION: Anything that decreases Ca +2 cncentratin will cause relaxatin. Epinephrine in the bld causes vascular relaxatin. Epi binds beta2-receptrs t activate beta-adrenergic Pathway > higher levels f camp which results in decreased Ca +2 in cytsl. camp will facilitate pumping f Ca +2 back int SR. ATP: Lw levels f ATP will cause vascular relaxatin lcally, which shuld allw greater bld flw, greater perfusin, and hence mre ATP t deprived tissue. ATP-Dependent K + -Channels pen in respnse t LOW ATP. This leads t Hyperplarizatin > Vascular Relaxatin > greater bld flw t area. NO causes relaxatin, cvered later. VASOMOTION: Spntaneus actin ptentials can cause a cyclic change in vascular tne. Additin f NrEpi increases the rate f firing f thse actin ptentials > mre vascular tne. Hwever, actin ptentials are nt always required t cause sustained cntractin. ENDOTHELIAL-DERIVED FACTORS: Nitric Oxide EXPT: Acetylchline's (i.e. parasympathetic) effect n vessels depends n the presence f the endthelial cells. Add Ach t vessel with endthelial cells intact > relaxatin. Add Ach t vessel with endthelial cells remved > actually leads t cntractin! Prcess f NO-Mediated Vascular Relaxatin: Ach binds t endthelial cell. Ca +2 channels pen and Ca +2 purs int endthelium. 14

15 This makes the endthelial cell prduce NO frm Arginine, by up-regulating synthesis f the enzyme Cnstitutive NO-Synthase. Endthelium makes NO which diffuses t the underlying vascular smth muscle. NO then activates Guanylyl Cyclase, which prduces cgmp > leads t Ca +2 sequestratin and vascular relaxatin. L-Nitrarginine Methyl Ester (L-NAME): Inhibits NO-Synthase, blcking prductin f NO > arterilar cnstrictin > lwer bld flw t regin. ISCHEMIA-REPERFUSION: The danger in reperfusing ischemic tissue is that massive influx f O 2 can lead t xidative free radicals which damage endthelial cells. The free radicals have tw bad effects: They react with NO, leading t vascnstrictin and reduced perfusin f the area. They directly damage the endthelial membrane leading t increased vascular permeability which isn't gd (it can lwer bld pressure, etc.) SEPSIS: Causes vesicle t becme less sensitive t vascnstrictin. Phenylephrine has a lesser effect n septic vessels. It leads t higher NO via Inducible NO-Synthase. This is nt the same enzyme as cnstitutive NO-Synthase. The number f vascnstrictive alpha-receptrs is decreased. Basal Ca +2 levels are reduced r Ca +2 -channels dn't pen prperly. ADHESION MOLECULES: NO prtectively prevents expressin f adhesin mlecules, s that leuccytes dn't stick t vessel wall, which can lead t micrvascular injury. Hence we can't use L-NAME as a treatment fr Sepsis -- we need the NO t prevent sticking f bld cells, even if vasdilatin is an undesired effect. What we need is a drug that blcks nly Inducible NO-Synthase (made during sepsis) and nt cnstitutive NO- Synthase. We dn't have that (yet). ENDOTHELIN-1: Vascnstrictive agent prduced by endthelial cells. SLOW-RESPONSE: Endthelin is nt stred in vesicles. It is synthesized de nv. Thus it is a slw (lng-term) respnse. SYNTHESES: Preprendthelin > Big Endthelin > Endthelin. Multi step synthesis adds t slw respnse. EFFECT: Endthelin causes sustained vascnstrictin. The effect lasts lng! It causes increased levels f Ca +2 and thus increased vascular tne. It acts via alpha-adrenergic pathway (PIP/DAG > Ca +2 ) It als acts directly n Ca +2 -Channels. ISCHEMIA REPERFUSION: Endthelin is bad! It can be released alng with inflammatry mediatrs t cause further vascnstrictin when we want vasdilatin. LOCAL REGULATION OF BLOOD FLOW: We cntrl lcal bld flw by changing lcal resistance. Three factrs can change lcal resistance: Endthelial-Derived Factrs Mechanical Stretch f the vessel itself Intrinsic Factrs = lcally derived metablites Organ-Distributin f Bld Flw: Highest perfusin rates are in liver, kidney, and skeletal muscle. Kidneys have the highest Perfusin Index: The rati f perfusin t rgan size. It measures the relative amunt f bld that different rgans get per rgan mass. OXYGEN TAKE: T increase Oxygen Uptake by tissues, yu can therefre increase ne f tw things. Mst rgans increase O 2 - uptake by a cmb f bth things. Increase O 2 extractin. This is hw the KIDNEYS primarily get mre xygen. Increase bld flw. This is hw the HEART primarily gets mre xygen. The heart can't increase O 2 -extractin because it is already extracting abut the maximum amunt pssible. O 2 -Extractin = Arterial PO 2 - Venus PO 2 Oxygen is extracted by simple diffusin. T increase xygen extractin, increase the surface area f capillaries expsed t tissue. 15

16 Heart-Muscle has a high basal capillary cncentratin than skeletal muscle. Thus it has higher xygen extractin. Pre-Capillary Sphincters can be dilated t perfuse mre capillaries in the capillary bed. Specific Organs: HEART: It has a high xygen extractin, s the nly way t increase O 2 uptake is t increase bld flw. KIDNEY: It has a lwer xygen extractin. It can actually increase O 2 extractin t increase O 2 - Uptake. AUTOREGULATION: Mechanism: Keep cnstant flw and capillary pressure (i.e. filtratin) in the face f changing systemic pressures. Lwer lcal pressure > Vasdilate > lwer resistance > maintain higher flw and higher capillary pressure. Higher lcal pressure > Vascnstrict > higher resistance > maintain lwer flw and lwer capillary pressure Tissues: Autregulatin wrks particularly in the kidney, heart, and brain. Limits: Autregulatin nly wrks in a limited range f pressures. Vessels wn't change diameter past their minimum and maximum. MYOGENIC RESPONSE: Sudden stretch f vascular wall can lead t vascnstrictin t cunteract the higher bld-vlume. Wrks in cnjunctin with the metablic respnse t maintain bld flw. There are tw types f arteriles: One prduces Actin Ptentials t have rhythmic vascnstrictin (vasmtin) The ther type des nt prduce actin ptentials. Bth types are still subject t the mygenic respnse. Mechanism: AP-Capable Arteriles: Stretch > increased frequency f AP-firing > higher vascular tne. AP-Incapable Arteriles: Stretch > deplarizatin f vascular smth muscle > Ca +2 influx and higher vascular tne. METABOLIC RESPONSES: Wrks in cnjunctin with the Mygenic Respnse t maintain bld flw. METABOLIC HYPOTHESIS: Vasdilatr Metablites are made lcally in respnse t hypxia and pr bld flw, in rder t increase bld flw. The metablites are then washed away when bld flw increases again, dispsing f their effect. HYPOXIA: Hypxia leads t a decrease in intracellular ATP, which ultimately leads t vasdilatin. K + -ATP CHANNELS: They kick K + ut f the cell in exchange fr bringing ATP in. They pen in respnse t lw ATP levels. Hypxia > lw intracellular ATP > Open K + -ATP Channels > K + purs ut f cell > membrane hyperplarizes > smth muscle relaxatin. PROSTACYCLIN (PGI 2 ): Prstacyclin may be released by endthelial cells in respnse t hypxia > ptent vasdilatin in a paracrine manner n neighbring smth muscle. ACIDOSIS: Acidsis in smth muscle directly causes hyperplarizatin f smth muscle membrane > vasdilatin. Acidsis means CO 2 levels in tissue are high. CO 2 <====> H 2 CO 3 <====> H HCO 3 ADENOSINE: Adensine is an indicatr that the target tissue is ut f ATP (as ppsed t the smth muscle itself). Adensine is membrane-sluble while ATP, ADP, and AMP are nt. S when the cmpunds gets dwn t the Adensine level, it can then leave the cell t affect the neighbring smth muscle. Adensine is a ptent vasdilatr. AUTOCOIDS: Histamine, Bradykinin, Sertnin, Prstaglandins, Leuktrienes. POTASSIUM: Ptassium regulatin is especially imprtant in the brain and in skeletal muscle. SMALL AMOUNTS OF K + In bth tissues, extracellular K + cncentratin ges up because f repeated firing f actin ptentials. 16

17 This results in release f vasdilatr-factrs (NO, PGI 2 ) and in membrane hyperplarizatin f vascular smth muscle. HUGE (PHARMACOLOGICAL) INCREASE IN K > deplarizatin f muscle membrane > vascnstrictin. INTERSTITIAL OSMOLARITY: ACTIVE HYPEREMIA: Bld flw changes in prprtin t changes in metablic activity f the rgan. Occurs in Skeletal Muscle. Lactic Acidsis in skeletal muscle > Vasdilatin f vasculature. In Active Hyperemia, the metablic activity f the target tissue (i.e. skeletal muscle) is changing, and that's what causing the vasdilatin. REACTIVE HYPEREMIA: The shrt-term increase in flw fllwing temprary ischemia t a regin. Bth mygenic and metablic effects are playing a rle in causing the vasdilatin. In reactive hyperemia, the metablic activity f the target tissue des nt change, whereas in active hyperemia, it des. REGIONAL CIRCULATIONS: CEREBRAL CIRCULATION: Cerebrspinal Fluid: Nrmally has a lwer prtein cntent than bld. Cerebral Vasculatures have very pr sympathetic innervatin. Hence in the Cushing Reflex, massive sympathetics dn't cause cnstrictin f vessels in the cerebrum (which they shuldn't!) Regulatin f Flw: It is primarily K + -Mediated. We can get higher extracellular K + and vascular hyperplarizatin by tw surces: Firing f neurns withut replarizatin. K + -ATPase kicks ut K + in exchange fr ATP, at lw intracellular ATP levels. The brain is very sensitive t changes in PCO 2, but nt s much t changes in PO 2. CORONARY CIRCULATION: Regulated almst entirely by lcal factrs. Increase cardiac wrk > increased crnary bld flw. SYSTOLE: Crnary bld flw decreases, as the vessels are squeezed as the mycardium cntracts. There may even be sme retrgrade flw f bld during systle. DIASTOLE: Crnary bld flw increases. CARDIOVASCULAR CONTROL MECHANISMS PARASYMPATHETIC DILATORS: They cause lcal vascular relaxatin. Parasympathetics d nt have an imprtant effect n systemic bld pressure. Vasactive Intestinal Peptide (VIP): This neurtransmitter is released directly nt the smth muscle cells t cause relaxatin. Nitric Oxide (NO): The nerve terminals cntain Nitric-Oxide Synthase. NO, when released by nerve terminals, als acts directly n smth muscle. NOCICEPTORS: Sensry receptrs t nxius chemicals r txins. They als cause lcal vasdilatin. Tw peptides are released by Nciceptr Nerves: Substance P Calcitnin Gene-Related Peptide (CGRP) TRIPLE RESPONSE OF LEWIS: Wheal and flare respnse t a lcal irritant. First, a small red area develps. This is due t degranulatin f mast cells > lcal vasdilatin. 17

18 Secnd, a blanched raised area develps arund the small red area. Third, a reddened flare (vasdilatin) radiates arund the irritated regin. The flare is due t highly branched nciceptr nerves that are distributed thrugh the skin. The Nciceptrs release SP and CGRP in the area t cause vasdilatin. LOCAL NEURAL RESPONSE: The nciceptr reflex des nt g thrugh the CNS! If yu cut the Drsal Rt (prximal t the cell bdy), the neural respnse still ccurs. This shws that the reflex signal is independent f the CNS. If yu cut the peripheral nerve (distal t the Cell Bdy), then Wallerian Degeneratin ccurs and the reflex n lnger happens. Capsaicin (red-pepper stuff) is an irritant that, if applied t the skin fr a perid f time, will veruse and numb the nciceptrs. Thus it is a treatment that can prevent the irritant respnse. SYMPATHETIC CONTROL OF VASCULAR MUSCLE: This is the primary shrt-term mediatr f TPR and hence arterial bld pressure. Sympathetics are f curse vascnstrictive, with tw pssible exceptins: beta2-receptrs are vasdilatry. They are mst respnsive t Epinephrine (which is nt a neurtransmitter), but they are respnsive t NrE at huge dses). Dgs and cats have sympathetic chlinergic nerves (like eccrine sweat glands) that are vasdilatry. Nrepinephrine: Released frm small dense-cre vesicles in the sympathetic varicsity. Nrepinephrine is released by any deplarizatin, f any impulse frequency. NrE binds t alpha1-receptrs n smth muscle t increase Ca +2 cncentratin and effect smth muscle cntractin. NrE has a very high affinity fr alpha1-receptrs. Epinephrine des nt. ATP: Released frm small dense cre vesicles in the sympathetic varicsity. ATP is released by any deplarizatin. It wrks at impulse frequencies as lw as 2Hz. ATP binds t Purinreceptrs (P-Receptrs) t cause deplarizatin f the smth muscle membrane. Each ATP dense-cre vesicle yields +10mV f deplarizatin. Tw simultaneus deplarizatins (ttal f +20mV) are required t generate smth muscle actin ptential. Neurpeptide-Y (NPY): Released frm large dense-cre vesicles in the sympathetic varicsity. Neurpeptide-Y is nly released by repeated deplarizatins (i.e. strng sympathetic stimulatin). It is nly released if the impulse frequency is 8Hz r faster. NPY binds t its wn Y-Receptr. COTRANSMISSION: NrE, ATP, and NPY have additive effects. At high impulse frequencies, NPY facilitates the release f additinal NrE. The summatin f signals will lead t strnger cntractin f vascular smth muscle, up t a pint. MODULATION OF SYMPATHETIC NEUROTRANSMITTERS: Ctransmissin principles are based n increased likelihd that a dense-cre vesicle will fuse with the pre-synaptic membrane. The higher the impulse frequency, the mre likely that is t ccur. AUTORECEPTORS: Simple negative feedback. There are receptrs fr NrE, ATP, and NPY. When the respective hrmnes bind, they inhibit further release f the neurtransmitter (i.e. they decrease the likelihd f vesicle fusin). HETERORECEPTORS: These are pre-synaptic receptrs that bind t ther substances t inhibit r excite release f neurtransmitters. Inhibitry Heterreceptrs: Acetylchline binds t muscarinic receptrs n the sympathetic varicsity t inhibit the release f NrE. Prstaglandins, Sertnin, and Histamine can all bind t inhibitry heterreceptrs as well. Excitatry Heterreceptrs: ANGIOTENSIN II will bind t excitatry receptrs t prmte further release f NrE > vascnstrictin. AUTONOMIC TONE: Heart rate and vascular tne is determined by the relative amunts f sympathetic and parasympathetic cntinual stimulatin. PARASYMPATHETIC TONE: The Vagus Nerve (CN X). Vagal tne fr the heart and abdmen riginates frm: 18