Ch_15_and_16_combo_notes_Alterations_BP_and_Flow.docx

Chapter 15 + ch 16 – Alterations in Blood Flow and Blood pressure PA Pathophysiology These notes take the first half of ch 16 and the first half of ch 15 to explain the physiology of the vascular system as a whole before looking at the pathophysiology (last half of 15 and 16). Therefore, the materia...

Chapter 15 + ch 16 – Alterations in Blood Flow and Blood pressure PA Pathophysiology These notes take the first half of ch 16 and the first half of ch 15 to explain the physiology of the vascular system as a whole before looking at the pathophysiology (last half of 15 and 16). Therefore, the material here is based on what is in the text but may not exactly follow the text in order the entire time. I have put page references in the notes when needed. Chapter 15 – Alterations in Blood Flow What are the major factors influencing blood flow? How does altering vessel radius affect resistance and consequently blood flow? How do length, fluid viscosity, and vessel radius affect resistance? What is Poiseuille’s law. What place in the vasculature is mostly responsible for regulation of vascular resistance? What place in the vasculature has the most (or the least) cross sectional area? Where in the vasculature is the blood at its highest velocity? Why? What is the difference between turbulent and laminar blood flow? Give examples of where each can occur in the circulation. Where in the vasculature are vessels most compliant? Why? What is the starling hypothesis and how does alterations in the factors that make the starling formula affect capillary fluid transport? What happens to the Starling Forces, and thus net filtration, in hypertension, lymphatic blockage (cancer), increased capillary permeability (septic shock), other diseases states. starling's microcirculation forces. - what factors would have to change to cause edema? What factors primarily control blood flow? Where do you think is their primary site of action in the vasculature? What vascular abnormalities affect blood flow? How and where do thrombi form? How are they treated? What is a major complication of embolism (why is it so dangerous?) Where do pulmonary emboli usually form? What about cerebral emboli? What causes atherosclerosis? Explain the step in atherosclerotic plaque formation. What are the risk factors and treatments for plaque formation? What are aneurysms? How can they affect blood flow? Describe how blood moves from capillaries back to the heart? What is the ‘venous pump’? What is valvular incompetence? What are the consequences of it? What is deep vein thrombosis? Chapter 16 – Alterations in Blood Pressure What are the major factors influencing blood pressure? How does altering peripheral resistance and/or blood volume affect BP? What causes the pressure difference between the left ventricle/aorta and the right atrium? What causes the difference in SBP and DBP? How do you estimate MAP? Is this always an accurate measurement. Why is DBP mathematically favored in the calculation of MAP? What factors influence stroke volume? What about HR? Describe the extrinsic and intrinsic factors affecting blood flow to tissues. What receptors are activated by the SNS at the vasculature; at the heart? What is the effect on BP What are the baroreceptors? Where are they located? What do they do? What is the Frank-Starling law? How does EDV influence SV. How does contractility affect this relationship? What Determines SV, HR and CO? What is contractility? What affects it? How is it different from SV? What is afterload? What affects it? How does it affect other cardiovascular functions (SV, SVR, CO, heart workload?) What are the hormonal influences on BP? How does each system work to modify BP? Describe local autoregulation – both the metabolic and myogenic paths. Why do the lungs have a lower pressure than the peripheral circulation if the same blood volume is perfusing each at any one time? What is hypoxic vasoconstriction and why it is useful in the lungs? What are the risk factors for hypertension? Describe primary vs secondary hypertension. How are the systems that regulate BP linked to the malfunctions that lead to hypertension? What is the “Cushing’s Response”? What is the trigger and the symptoms. Why do they occur? What are the consequenses of chronic hypertension on the heart, the vasculature, the brain, kidneys, the lungs or peripheral vasculature, and retina? Describe the link between hypertension and left and right heart failure. What are some of the treatments of hypertension? On what 2 main factors of BP regulation do they concentrate? Outline Pg383-392 ch 15 Organization of the Circulatory System (I am skipping this section) Vessel and Lymphatic Structure Arteries and veins have three distinct layers. The intima, the innermost layer, is composed of a single layer of endothelial cells. The media, or middle layer, is composed of smooth muscle and elastin. Media is thicker in arteries than in veins. the adventitia, the outermost layer, is composed of supporting connective tissue. (fig 15-4) Capillaries have only a single layer of endothelial cells. The permeability of capillaries is determined by how tightly the endothelial cells join together. Lymphatic vessels resemble veins, having thin walls and valves. Arteries have smooth muscle that is tonically (always) contracted to some degree. The muscle tone here gives some resistance to the flow of blood through the arteries and therefore pressure is generated. Veins do have some smooth muscle but they are more elastic. They stretch and therefore hold more volume of blood and do it at a lower pressure. Sometimes veins are called the ‘capacitance vessels’ because they have the capacity to hold blood more than arteries normally do. compliance The more compliant the vessel the more distensible it is. Therefore, it will have less pressure it at the same volume. Veins are more compliant than arteries therefore they are capable of holding more blood volume at lower pressures Veins are known as ‘capacitance vessels’. So, if your BP completely fails then more blood will ‘pool’ in the venous circulation due to its compliance. Fluid tends to collect in the venous circulation if pressure builds up elsewhere (like if there is edema in tissues) Principles of Flow - Hemodynamics of Circulatory Flow Determinants of Flow Pressure gradients, Enable blood to flow from high to low areas of pressure (artery to vein) Change in P is arterial pressure minus central venous pressure (CVP). It is this pressure gradient drives blood flow Resistance - Inversely proportional to flow. (increase resistance, you will decrease flow) Determinants of Resistance (R) Viscosity (n) Increasing viscosity will increase resistance, which decreases flow Think sipping a milkshake vs water Viscosity is proportional to resistance Length (l), Poiseuille’s law: Resistance (R) = 8 (n) l or R proportional to l n (3.14) radius4 r4 *The point – the viscosity of the fluid, the length of the space and most importantly the radius of the vessel help determine resistance and influence flow through the system. Radius (r) – see ‘calculations’ page at end of notes. Primary determinant of resistance (r4) Resistance inversely proportional to radius4 *if you double the radius you decrease resistance 16 times. If you apply this to the Q=P/R relationship – the blood flow increases 16x when radius is doubled. So, Q is proportional to r4 (analogy) Garden hose vs cocktail straw. Which will have highest flow with the same pressure? The one with the largest diameter. So what does all this mean? It means that Flow is proportional to the change in the pressure gradient (generated by the heart) and the radius of the vessel to the 4th power. The vessel radius is by far more important to flow regulation than anything. A simplified version of all of this physics is… Vascular system primarily uses resistance to alter blood flow. (can’t alter length and can’t alter viscosity quickly). So, vasodilation and vasoconstriction are two primary ways in which the body regulates blood flow. Arterioles are the primary sites of regulation of vascular flow. Drugs/Therapies that affect the arterioles have more direct effects on BP and blood flow. Blood Velocity (I am skipping this section but its in your notes as an FYI) Velocity is defined as the flow of blood past a specific point in a given unit of time. Velocity of blood traveling through a vessel is inversely proportional to the cross sectional area of the vessels. (fig 15-10) The more area in which there is for a unit of blood to travel the slower it will travel Ex – the aorta has the same blood flow as all the capillary beds but much lower cross sectional area. So the blood moves through the aorta more rapidly (higher velocity). Laminar vs turbulent flow blood in the center of a vessel moves more smoothly and without as much turbulence as blood near the vessel wall due to friction between blood cells and the vessel wall . the slower moving blood at the vessel wall can cause aggregation of clotting factors and increase the risk for a thrombus formation. Turbulent blood flow often occurs in vessels with a high velocity (aorta and major arteries) and at branches in the vessel. (fig 15-12) Ex – like a large rock in the middle of a stream disrupts the water’s smooth flow down the middle of that stream. Turbulent flow can be auscultated as a bruit Examples in the body of turbulent flow: Often occurs at sites of atheroscelerotic plaque buildup. heart murmur sounds and sometimes in large arteries chest congestion can cause wheezing due to turbulent airflow Function of the arterial and pulmonary systems (ch 16 p410-415) Arterial pressure pulses Systolic BP (SBP) – result of heart ejection into arteries and the lack of compliance of those vessels. Diastolic BP (DBP) – result of the elastic recoil of the aorta pushing blood to distal arteries. Pulse pressure (PP) = SBP-DBP (see fig 16-1) Mean Arterial Pressure – average blood pressure throughout cardiac cycle. Heart spends more time in diastole so when calculating MAP, DBP is weighted more. MAP = [systolic BP + (2 x Diastolic BP)] / 3 Only an estimation of MAP because as heart rate rises, the system spends less time in diastole and this formula doesn’t work so well. Determinants of blood pressure (an overview… more detail starting in IV below) BP = change in P (from left ventricle to right atrium) Therefore Cardiac output (CO) is influenced by both the heart rate and the amount of blood exiting the heart with each beat (stroke volume). A change in either will proportionally change CO. What determines stroke volume Preload – amount of blood filling the heart before each contraction. Contractility – the amount of force the myocardium generates to eject the blood from the ventricles Afterload – the resistance to the ejection of blood out of the ventricle. What determines HR Balance of SNS and PNS influence on the heart. This system is strongly influenced by the baroreceptors (see below). What determines SVR Look at Pouiselle’s law – viscosity, length, and most importantly radius of vessels. Determinants of Blood Pressure = Cardiac Output and Vascular Resistance Intro: What determines Cardiac Output????? = SV and HR Stroke Volume (the amount of volume pushed out of the heart with every beat. Heart Rate = the number of beats per minute of the heart. Determinants of Stroke Volume Preload – how much blood you give the heart before contraction Preload is proportional to venous return. Refers to the amount of blood presented to the heart before systolic contraction = end diastolic volume (EDV) In general, the EDV will help determine the SV (stroke volume) This is the “Frank-Starling” law, - The more the ventricle is filled with blood during diastole (EDV), the greater the volume of ejected blood will be during the resulting systolic contraction (stroke volume). How this happens The force that any single muscle fiber generates is proportional to the initial sarcomere length (known as preload), and the stretch on the individual fibers is related to the end-diastolic volume of the ventricle Blood filling the ventricle stretches the ventricle muscle. This causes the actin and myosin to be stretched out to an optimum point. The cross bridges can be formed and the muscle can contract a greater distance if the starting point is a stretched muscle. The heart can therefore adjust its SV from one beat to another based on the venous return. There is a limit to this – overstretching (which almost never happens in the heart unless its chronically diseased) can limit the heart’s effective contractions. Anything that increases blood volume will likely increase SV – up to a point…. Venous return - Skeletal muscle movement and venous valves help propel venous blood back to heart. This increases preload on the heart and can help SV. Without venous return from the legs, blood pools at the feet. What happens to venous return? What happens to preload? What about stroke volume, Cardiac output, blood to te brain? All go down so…. You go down. Hence the reason for the flight suits in fighter pilots which constrict the legs to push blood back to the heart. If not, when they experience excessive G forces that pull blood to their feet they pass out. Contractility – the force of the heart’s contraction Depends on Contractile proteins ATP availability Ca++ availability – most variable in the heart (ionotropic drugs can influence contractility). Any factor that enhances availability of cytoplasmic free Ca2+ will increase contractility. SV and contractility Contractility is not exactly the same as SV – although they are related. Contractility is the ability of the heart to contract and is independent of preload. Increased contractility increases stroke volume by causing a greater percentage of the ventricular volume to be ejected. Can be decreased by Damage to heart (less functional contractile proteins) Hypoxia (less ATP made) Anything that decreases Ca+ release, or speeds up its removal from the cell. Afterload Afterload is determined primarily by the resistance of the arterial system. Left ventricular afterload – due to resistance to ventricular ejection of blood. determined by BP can be affected by aortic (or aortic valve) stenosis. Right ventricular afterload – Determined by pulmonary pressure Can be increased if lungs are congested Increases work load on the heart (therefore O2 demand). Increased afterload will decrease stroke volume. To maintain CO the HR usually will increase. Cardiac Workload Any factor that increases heart rate, preload, contractility, or afterload will increase the workload of the heart. Afterload is the one that will increase cardiac workload without increasing cardiac output. Determinants of Heart Rate Primarily determined by balance between SNS and PNS Factors that increase heart rate include: low blood pressure (baroreceptors), emotions. Etc. (anything that impairs O2 delivery to tissues can increase SNS influence on the heart). Extrinsic (Autonomic NS control) SNS is primary factor in regulation of blood pressure. Vasomotor center in medulla oblongata causes NE release at smooth muscle of most arteries (alpha 1 adrenergic receptors). - vasoconstriction Vasomotor tone – basal activity from medulla causes some low level of vascular tension at almost all times. Increased activity in vasomotor center can cause excess vasoconstriction => increased SVR => increased BP. Decreasing SNS influence on the vasculature can decrease vasomotor tone. PNS (parasympathetic) has little effect on vascular tone (but large effects on the heart). Epi released from adrenal acts on primarily B2 adrenergic receptors on arterial vasculature of skeletal muscle. – vasodilation. In higher doses it can activate alpha adrenergics in other capillary beds to cause vasoconstriction (increased SVR => increased BP) Baroreceptors (from ch 16 pg 412) – see also supplemental figure 1 Stretch receptors located in the carotid sinus and the aortic arch. When stretched due to high pressure they inhibit the cardiovascular control center in the medulla. This causes a decrease in SNS outflow, and an increase in Parasympathetic outflow, to the heart and vasculature. This decreases both SVR and CO and thereby decreased BP. If constantly stimulated (with chronic hypertension) the baro ® can be reset to a higher level – they can adapt. What stimulates Baro ® - high BP What does the Baro® reflex do – inhibits SNS and stimulates ParaNS What is the effect of Baro® stimulation – lowers BP ***negative feedback reflex**** Athletic Training and SV and HR Athletic training (especially cardiovascular training) makes the heart muscle stronger, like most any other muscle. This increases contractility Increased contractility increased SV CO, even at rest. If BP is normal, and SV is increased…. What would expect HR to be? Why? An Olympic athlete’s resting HR is likely very low (say…. 55-65 bpm). This is because CO is being maintained through an elevated SV due to very good contractility. See Frank-Starling curve. At the same EDV, with elevated contractility you can get a higher SV. This is beneficial to blood flow to the myocardium. Blood flows through coronary arteries primarily during diastole when the heart muscle itself is relaxed. The more diastolic time, the more blood can flow to the myocardium. Also, more diastolic time means more opportunity to fill a relaxed ventricle with blood. This also boosts preload and enables better SV. (F-S effect again.) In an athlete, it also creates more room for HR to eventually increase to maximal levels for performance. Person A: Olympic athlete. Resting HR is 60. Maximal HR is ~200 (makes the math easy). They can increase their HR by 140 bpm and therefore their CO by ~230% due to only the increase in HR (140 is 230% of 60) Person B: not an athlete. Resting HR is 75. Maximal HR is ~200. They can increase their HR by 125 bpm and therefore their CO by ~160% due to only the increase in HR (125 is 160% of 75). Having a lower HR at any given exercise level allows for better cardiac function. Endocrine Function of the Heart Endocrine influences of BP. NE and EPI from the medulla act similar to neural stimulation of heart and vasculature (increase BP). Short term usually. Renin-Angiotensin Aldosterone system – (RAAS) is involved in longer term BP control via regulation of blood volume Renal hypoperfusion, decreased Na+ delivery, and the SNS can activate Renin (and aldosterone) release Na+ retained => water retention => blood volume increase => increased preload on heart => increased SV => increased BP. => angiotensin II production => vasoconstriction => increased SVR => increased BP. => angiotensin II production => stimulate thirst centers increase blood volume and pressure => angiotensin II production => stimulate ADH release from brain increase blood volume and pressure So ACE inhibitors or Angiotensin Receptor Blockers (ARBs) help to lower BP in 4 different ways. Atrial Naturetic peptide (ANP) More of chronic regulation of BP When blood volume increases => Stretch receptors in atrial myocytes cause release of ANP. ANP causes increased renal perfusion and increased glomerular filtration rate. Increased Na+ and water excretion (naturesis) And vasodilation Inhibits Renin (& therefore aldosterone) and ADH release. Defect in ANP may lead to hypertension. ADH and BP control Water retention at kidney cause increase in BP. Other neuroendocrine mediators NO- nitric oxide Short acting vasodilator Inhibited by Angiotensin II Endothelin – 1 Vasoconstrictor Activated by angiotensin II Thromboxane A2 Released from platelets Vasoconstrictor Inhibited by aspirin Intrinsic (local autoregulation) (back to ch 15 pg 393-394) Ability of the tissue to maintain steady blood flow despite arterial blood pressure changes Can be done by secretion of metabolic factors that act on local vasculature. (metabolic hypothesis) CO2, lactic acid, histamine, etc. Can be done by pre-capillary sphincters reflex action to alterations in pressure. (myogenic hypothesis) If pressure is high the sphincters will contract to limit the high pressure the capillaries are exposed to. They may also relax if arterial pressure decreases. Mediated by NO, PGs, prostacyclins, etc. Pulmonary BP Normally lower than peripheral arterial vasculature because it is more compliant (fig 16-1) Lower pressure advantageous because Blood doesn’t have to travel as far to get to lungs (thoracic cavity) Fragile capillaries can’t handle the high pressure the systemic arteries have. Same cardiac output goes through lungs as does the peripheral circulation. Normal pressure = 23/8 mmHg therefore MAP =13 Hypoxic Vasoconstriction Unique property of pulmonary vasculature (unknown mechanism) In systemic vasculature the vessels dilate when hypoxic to maintain O2 delivery. Hypoxic pulmonary vessels constrict (therefore redirecting blood away from poorly ventilated alveoli). Dynamics of Microcirculation (Starling Hypothesis) – (ch 15 pg 392-393) How does fluid move across capillary membranes? Dependent of the interaction of several forces Pressure gradient between capillaries and the interstitial space Normally a gradient pushing fluid into tissue (interstitium) Osmotic gradient between capillaries and the interstitial space Plasma proteins (especially albumin) in the blood make the osmotic pressure here higher than the tissues. Permeability of the capillary membrane Starling Equation Jv = Kf [(Pc – Pi) – ( ∏c - ∏i )] Jv = net fluid movement (ml/min) Kf = permeability of capillary membrane (ml/min x mmHg) Pc – pressure in capillary (mmHg) Pi - pressure in interstitial space (mmHg) ∏c - osmotic pressure in capillary (mmHg) ∏I – osmotic pressure in interstitial space (mmHg) There is normally a net filtration at the capillary bed because the net starling forces of the arterial and venous capillaries are slightly positive. The excess fluid is normally removed by lymphatics. Too much fluid in tissues = edema. *Questions to ask yourself: What happens to the Starling Forces, and thus net filtration, in hypertension, lymphatic blockage (cancer), increased capillary permeability (septic shock), other diseases states? General Mechanisms that Cause Altered Flow (ch 15 pathophysiol pg 398-408) Blood Vessel Obstruction Thrombosis – abnormal blood clot formation Etiology can be caused by local injury to heart or heart valves or can form in area of low blood flow (stasis of blood) or turbulent blood flow. Can lead to more turbulent blood flow and cause thrombus to grow. Sx Location leads to symptoms In venous system – edema In arterial system – ischemia/hypoxia of distal tissues. Can lead to pulmonary or brain embolism if clot breaks free. Thrombi often form in legs so leg pain is a common symptom Tx Preventative measures as anti-coagulant therapy (coumadin, heparin, etc). which block the clotting cascade. Thrombolytics – clot buster drugs break down existing clots. TPA, streptokinase, etc Embolus Clot that breaks free and is normally lodged in small capillaries Bad news if in the brain or lungs. – block blood flow. Left sided embolism - If lodged in the brain (CVA) it likely was formed in the chambers of the heart. Right sided embolism: If lodged in the lungs it likely was formed in the slow moving blood of the lower extremities – moved through the venous blood – past the right ventricle to the small capillaries of the lungs. Tx Normally thrombolytics and anti-coagulants are used Surgical removal dependent on location of emboli Can implant blood filter in vena cava to trap emboli - preventative. Other emboli Fat Bacterial Tumor Air bubble Alterations in Arterial Flow Arteriosclerosis/Atherosclerosis Arteriosclerosis – hardening of arteries One type of arteriosclerosis is atherosclerosis excess lipid deposits on luminal wall Causes decreases in luminal diameter. Tends to form plaques in large and med sized arteries. Especially coronaries = Coronary Artery Disease (CAD) Leads to heart attack (MI) Plaque formation linked to high cholesterol – specifically LDL (low density lipoproteins) in the blood. Also linked to chronic irritation (stress, smoking, hypertension etc) of vascular wall – allows lipids and serum proteins to aggregate in vasculature. Steps in plaque formation – progressive luminal shrinking. Endothelial injury Influx of lipids – especially LDLs Lipid buildup, smooth muscle cell buildup, macrophage recruitment Fibrous cap formation over site. Risk factors: Smoking and atherosclerosis endothelial injury vasospasm platelet aggregation catecholamine release – increase heart workload and metabolic demand synergistic effect on causing CAD with hypercholesterolemia, hypertension, or glucose intolerance. Hypertension and atherosclerosis often linked with other risk factors Hypercholesterolemia discussed above Glucose intolerance likely linked to abnormal carbohydrate and fat metabolism (hyperlipidemia) Stress Gender Women less likely – protective Estrogen effect? Genetic link Sx: based on poor blood flow to organs distal to plaques Tx: Reducing modifiable risks (improve diet, quit smoking, exercise) Anti-cholesterol meds (reduce absorption of Chol, increase its breakdown, or block its blood carriers, etc) Angioplasty – inflate a balloon at site of plaque to expand lumen (temporary fix b/c plaque likely to build up within 3-5 yrs). Stent – surgically insert cannula to keep artery open. Bypass surg – use leg vein (or synthetic) to replace blocked artery (usually coronary artery). Vein takes on structural similarities of artery. Vein normally only lasts 5-7 yrs before plaque build up again. Aneurysms Localized areas of artery weakening. Can decrease blood flow distal to site and localized bleeding if aneurysm ruptures. Sx Increased intracranial pressure (if located in cerebral vasculature) If the vessel is damaged (dissecting aneurysm) sharp pain at location (or ‘referred pain’ area) and signs of hypovolemic shock may result. Other symptoms caused by ischemia of distal tissue – paralysis, paresis. Tx Normally surgical repair if accessible (graft insertion, clamping of aneurysm). Lower blood pressure – vasodilators, Ca++ channel blockers (decrease cardiac output), etc. Alterations in venous flow Etiology When venous valves do not function properly blood can pool in those veins. Can occur in superficial veins (varicose veins) or deeper veins (DVT) Due to excess blood pooling in veins and over stretching of vascular tissue. Superficial veins ➔ superficial venous thrombosis (also called phlebitis or superficial thrombophlebitis) Unlike deep veins, superficial veins have no surrounding muscles to squeeze and dislodge a blood clot. Therefore, superficial venous thrombosis rarely causes a blood clot to break loose (embolism) Sx: can start with redness and itching or ‘heaviness’ in legs and lead to localized thrombi formation. edema (back up of fluid in veins => back up of fluid in tissues) Dx: usually by Sx but ultrasound can be used if in question. Tx Sx management: analgesics (NSAIDs). Try to get blood moving again warm compresses exercise (increases in skeletal muscle movement help push blood out of veins) elastic stockings or elevation of feet. Break any clots anticoagulants angioplasty (bust up the clots with local surgery) if small and superficial (varicose veins) Cosmetic treatment = laser therapy to destroy vessels (collateral flow still intact so tissue is ok.) Surgical removal of veins Unlike DVT (below) it is unlikely that superficial venous clotting will lead to an embolus that lodges in the lungs DVT- Deep vein thrombosis Etiology stasis of venous blood in deeper veins can lead to aggregation of platelets and thrombus formation. Especially in legs – gravity pulls blood downward and vascular system has harder time pushing it back up to heart. Various causes Genetic condition that increases your risk of blood clots Cancer and some of its treatments (chemotherapy) Trauma (limits blood flow in a deep vein, due to injury, surgery, or immobilization) Long periods of inactivity that decrease blood flow, such as: Sitting for a long period of time on trips in a car, truck, bus, train or airplane Immobility after surgery or a serious injury ‘Coach class syndrome’ Pregnancy and the first 6 weeks after giving birth Being over age 40 (although a DVT can affect people of any age) Being overweight Taking birth control pills or hormone therapy Dx By symptoms Imaging using: Ultrasound, XRay w contrast dyes, More expensive but higher resolution= MRI, CT https://my.clevelandclinic.org/health/diseases/16911-deep-vein-thrombosis-dvt/symptoms--diagnosis Sx Acute edema or pain due to increased venous fluid volume and pressure on nearby nerves Tx anticoagulants to prevent thrombosis formation. Try to prevent the cause of fluid backup in veins Exercise, Weight loss Diuretics Elastic/Compression stockings (increase blood flow out of venous system). Surgical Removal of clot Prevention of clot getting to the lungs (vena cava filters)- filter often coated in thrombolytics too. Hypertension (ch 16 pathophysiology pg 416-427) Defn - Blood pressure above 140 mm Hg systolic and/or 90 mm Hg diastolic in an adult. Risk factors Age SBP may rise more quickly due to decreased compliance of arteries. = “isolated systolic hypertension”. Race Af Amer = higher risk Obesity Nutritional status High Na+ levels Perhaps linked to RAAS or ANP regulation. Classifications and Causes Primary high BP (most common) High blood pressure without an identifiable cause; Genetic predisposition is present, which can be influenced by environmental factors such as diet and lifestyle. Could be due to most any dysfunction in regulation of BP RAAS Sympathetic control Baroreceptor increase in set point Excess SNS output Malfunction in ANP Excess vascular endothelin release (newer area of research) Insulin dysregulation Hyperinsulinemia can lead to hypertension (even without DM) – unknown mech. Linked with hyperlipidemia Secondary high BP High blood pressure of known etiology; caused by Excess Renin renal artery stenosis, lack of renal blood flow leads to excess Renin release renal failure, poor excretion of Na+ and water can increase blood volume => hypertension Endocrine disorders Excess glucocorticoids (cortisol) – Cushing’s Excess mineralcorticoids (aldosterone) – Conn’s Syndrome (primary aldos). Excess catacholamines (NE and EPI) - pheochromocytoma Hyperthyroidism – permissive effect of SNS. Vascular disorders Also can lead to decreased renal blood flow => RAAS activation and further increases in blood volume and pressure. Arteriosclerosis can lead to decreased DBP because the elasticity of the vessel is decreased. This can mean the vessel doesn’t recoil after systole as well so the vessel doesn’t squeeze the blood inside it as much during diastole. It also means that the vessel doesn’t expand as much when lots of blood is pushed into it (during systole). Together this means pulse pressure (SBP-DBP = Pulse pressure) can increase PP > 40mmHg has been shown to increase mortality secondary to cardiovascular disease. http://content.onlinejacc.org/article.aspx?articleid=1126287 increased intracranial pressure (ICP), Cushing’s response. = If ICP rises so high that cerebral perfusion becomes decreased the pO2 in the blood can decrease. If pO2 drops below 50mmHg then the SNS (mediated by posterior hypothalamus and medulla) will be massively activated. This causes a large spike in BP (SBP > 200) as a last ditch effort to restore cerebral blood flow. Triad of Symptoms Elevated BP, Reduced HR, Irregular Respirations Sometimes included in this is an increase in pulse pressure=‘bounding pulses’ See flow chart on powerpoint for how this works. Due to failure of increased BP to penetrate brain and fix blood flow problem and the baroreceptors reflex reaction to the increased pressure. Autonomic hyperreflexia (remember this from the neuro section on spinal cord injury). certain drugs. Effects of High BP Cardiac Left ventricular hypertrophy – due to increased ‘afterload’ Higher systemic blood pressure means the heart has to push against a greater resistance. This causes increase in muscle mass (like going to the gym for the heart) This causes increased O2 demand from the cardiac tissue that is working harder. There comes a point where demand for O2 exceeds supply and the heart tissue becomes ischemic (hypoxic). Leads to increased risk for MI (myocardial infarction) = heart attack where heart muscle is damaged (usually permanently). This can lead to failure of the heart. Heart failure can lead to fluid backing up behind the failed ventricle. Fluid build up in lungs if left heart failure (congestive HF) Fluid build up in systemic circulation if Right HF Vascular Stress on vascular wall can lead to weakened vessels Aneurysms Hemorrhage Accelerated atherosclerotic plaque buildup Damage to renal arteries can lead to renal failure Check for proteinurea in hypertensive patients Damage to retinal arteries can lead to vision impairment. Damage to cerebral arteries can increase risk for CVA or brain aneurysms. Signs and Symptoms of High BP Very few outward Sx until hypertension is advanced. Signs of left heart failure (more in ch 19) Pulmonary congestion Difficulty breathing (dyspnea) Fatigue Hypertrophy can appear on chest X Ray EKG changes Left HF can often lead to right heart failure Pulmonary congestion can increase afterload on the right heart. This can lead to venous blood pooling and tissue edema. Management of High BP Center on decreasing blood volume or decreasing vascular resistance. Lifestyle changes Low salt and fat intake, limit EtOH, weight loss, moderate exercise, Na+ and EtOH can hinder antihypertensive drug effectiveness. Pharmacologic Therapy Diuretics Block kidney reabsorption of fluid. Beta blockers Block beta adrenergic receptors at the heart decrease HR and SV by blocking Ca+ release needed for muscle contraction and for Action potential generation in the heart. Alpha receptor blockers Centrally or peripherally (at vasculature) decreasing SNS influence on vascular resistance. Calcium channel blockers Aimed at limiting Ca++ release in the smooth muscle of arterial vasculature. This reduces the tension there which reduces the SVR and consequently BP. ACE inhibitors or Angiotensin II Receptor blockers/modulators ACE inhib: Block conversion of angiotensin I to II in the lungs effectively limiting the renin-angiotensin system function. ARB: block AngII effects Both: Decrease fluid and Na+ retention from the kidneys Also good to use in heart failure and diabetes Hypertensive Crisis Short term but severe hypertension can be managed by powerful IV drugs that vasodilate, decrease heart SV or HR, and/or decrease SNS outflow. Low BP (covered with ch 20-shock) Supplemental figures 1. SAMPLE CALCULATIONS: Poiseuille’s law: R = 8 (n) l or R proportional to l n (3.14) radius4 r4 *The point – the viscosity of the fluid, the length of the space and most importantly the radius of the vessel help determine resistance and influence flow through the system. 1. IF N= 100 Length = 200cm Radius (r) = 4 Then Resistance (R) = 199 If length is doubled (400cm) then Resistance = 398 So…. Double the length – double the resistance. 2. If resistance (large R) is doubled (see #1) then flow is cut in half Q=change in P / R Q = (120-90) / 199 then Q = 0.151 Q = (120-90) / 398 then Q = 0.075 3. Lets look at radius of the vessel. If N = 100 Length = 200cm Radius = 4 Then Resistance = 199 If radius is cut in half then Resistance increases 16x!!!! R = [8(100)200] / 3.14 (24) = [160000] / 3.14 x (16) = 3184 199 *16 = 3184 The point – Radius of the vessel is BY FAR the most important factor affecting vascular resistance and therefore blood flow. Starling Equation Jv = Kf [(Pc – Pi) – ( ∏c - ∏i )] Jv = net fluid movement (ml/min) Kf = permeability of capillary membrane (ml/min x mmHg) Pc – pressure in capillary (mmHg) Pi - pressure in interstitial space (mmHg) ∏c - osmotic pressure in capillary (mmHg) ∏I – osmotic pressure in interstitial space (mmHg) Assuming constant Kf in all capillaries At arterial side of capillaries: J = ( 30 - 0 ) – (28 - 4 ) = +6mmHg - therefore net fluid movement out of capillaries here. At venous side of capillaries: J = ( 20 – 0) – ( 28 - 4) = -4 mmHg - therefore net fluid movement into capillaries here because the capillary pressure decreased. There is normally a net filtration at the capillary bed because the net starling forces of the arterial and venous capillaries are small but positive. The excess fluid is normally removed by lymphatics. Questions to ask yourself: What happens to the Starling Forces, and thus net filtration, in hypertension, lymphatic blockage (cancer), increased capillary permeability (septic shock), other diseases states. We will cover this when we cover the cardiac cycle but Mean Arterial Pressure can be calculated by the following formula. MAP = [systolic BP + (2 x Diastolic BP)] / 3