Microcirculation and Lymph Blood vessels Bulk flow: substances are swept along in the blood between organs. o rate of transport = flow rate X concentration Tissue rate of utilization of a substance: consider transport to and from the tissue transcap efflux rate = blood flow rate (arterial conc – venous conc) Linear flow velocity varies inversely with cross-sectional area; greater in narrow segments to maintain constant flow (consider all vessels in a category together). Total flow is the same through all segments of the CV system pg 206
capillaries: o RBC velocity in capillary: 1mm/sec o dwell time for RBC in capillary: 1-2 sec -> gas exchange; can become abbreviated in high flow states o endocytotic vesicles: flow produces mechanical stress; membrane is replaced/repaired via these invaginations o Types of capillaries: continuous: glycoprotein cell coats of adjacent cells fuse, tight junctions form in a “strip weld” arrangement; forms circuitous, water filled pore in which diffusion occurs closed fenestration: gaps between EC‟s not enough for high transcapillary flow; have fenestrations within an EC. Pores spanned by glycoprotein coat bridges. Cap integrity maintained by continuous basement membrane. See in glands, intestine, peritubular cap in kidney open fenestration: higly specialized, in glomerulus; permits very high flux of H2O and solutes. No glycoprotein coat bridging fenestration; do have intact BM, closed fenestration in podocyte
cells -> forms filtration slit, prevents large protein leakage. Filters about 180 L/day; 179 is reabsorbed Transcapillary fluid movement passive diffusion, controlled by: concentration gradient surface area for exchange diffusion distance permeability permeability of wall to diffusing substance lipid soluble substances: cross wall through entire SA small polar particles: cross through pores & between EC‟s pinocytosis: may account for a small amount of flux of proteins, hydrophilic substances o thermodynamic potential is proportional to concentration: net qty moving per unit time is: dq = conc grad (dC/dx) X D X Area dt D=diffusion coefficient= 1 6π X radius X viscosity thus, diffusion is inversely proportional to radius of molecule and viscosity of solvent; diffusion with temperature filtration: net fluid movement out of capillaries; about 20 L/day o water moves through pores due to hydrostatic pressure difference across membrane: Filtration = (P1-P2)r4π 8 X length X viscosity large proteins separated from small molecules depending on pore size hydrostatic pressure inside capillaries = 25 mmHg, is driving force for returning blood to RA. Tends to cause fluid to flow through pores into interstitium (hydrostatic pressure = 0) decreased by arteriolar constriction (more pressure drop across arterioles), increased by arteriolar dilation reabsorption: fluid movement into capillaries; balances hydrostatic force. About 17 L/day o osmosis: water moves back into capillaries due to higher concentration of proteins in there; moves toward side of “adulterated water” because flowing toward region of lower thermodynamic potential o continues until opposed by hydrostatic pressure difference across membrane o measure colloid pressure (protein conc) rather than thermodynamic potential: ∏ = concentration X R (gas constant) X absolute temperature oncotic pressure of plama is about 25 mmHg; oncotic pressure of interstitial fluid is about 0 Starling‟s hypothesis:
capillary behaves as semipermeable membrane across which H2O moves according to balance of hydrostatic and osmotic forces. intravascular hydrostatic pressure exceeds intracapillary oncotic pressure at arterial end; vice versa at venous end some proteins do leak out, returned via lymphatic system net filtration rate = K[(Pc-Pt) – (πc – πt)] o K = filtration coefficient, includes SA; how well acts as semipermeable barrier o Pc, πc: hydrostatic/oncotic pressure of capillary fluid o Pt, πt: hydrostatic/oncotic pressure of tissue
M pg 13
Edema Pc: venous pressure in heart failure πc: nephrotic syndrome (lose protein thru kidneys), liver disease ( prot synth) πt: filariasis, tissue injury (change in capillary perm allows cells, prots to move into tissues) Hypertensive pts. do not have edema as TPR, capillary pressure Lymphatic vessels; pick up about 3 L/day originate as open-ended tubes in connective tissue; remove excess H2O and proteins from interstitial spaces contain valves – control direction of flow back to heart flow promoted by compression of vessels by surrounding skeletal muscle, propulsive action of lymphatic wall smooth muscle
Peripheral Vascular Disease (*NOTE: several diseases are included here that were not covered in lecture, but were in Lilly) Arterial Ischemia Acute caused by embolic or thrombotic occlusion (in situ), dissection, or traumatic disruption most common etiology is embolism from cardiac thrombus (A-fib); also from thrombus overlying atherosclerotic plaque, paradoxical embolus through patent foramen ovale Dx: Pain Pallor Pulseless extremity Paresthesia Paralysis Outcome: dependent on severity of ischemia; target tissue; collateral circ Tx: restore blood flow during reversible phases, prevent reoccurrence o how much time can pass before becomes irreversible? Depends on temperature, type of tissue, extent of trauma, and severity of ischemia o signs of irreversible injury: rigor mortis, gangrene can produce systemic toxicity if revascularize at this point; K+ released from tissue produces tall T-waves; myoglobin can renal function o surgical thrombectomy, fibrinolysis, anti-coagulation therapy complications: re-embolism, thrombosis, compartment syndrome, intimal hyperplasia due to arterial injury Chronic o caused by arterial occlusion over a period of time o most common etiology is progressive enlargement of an atherosclerotic plaque = peripheral arterial occlusive disease femoropopliteal>aortoiliac>tibial o collateral circulation has time to develop; ischemia tends to be less severe o present with: claudication – ischemic pain with exercise, due to O2 demand>supply; fatigue, pain, weakness pain and numbness at night that is relieved by gravity (hang leg over edge of bed) severe: pain at rest, usually in feet/toes; predisposes to: ulcers that are slow to heal o Dx: Hx, presence of athero risk factors: smoking, hypercholesterolemia, DM, HT PE: loss of pulses distally, ulceration, signs of perfusion, bruits; delayed capillary refill, dependent rubor, nail thickening, muscle
atrophy, pallor, hair loss, shiny skin due to atrophy, occ. gangrene/necrosis measures of perfusion: ankle pressures (ankle/arm index) norm: > or = 1.0 claudication: .6-1.0 rest pain: .4-.6 tissue loss: <.4 o outcome: depends on severity of ischemia, control of risk factors. Mortality determined by extend of CAD o Tx: risk factors, exercise capacity; revascularization with disabling claudication or severe ischemia, pain at rest bypass operations, percutaneous transluminal angioplasty Aneurysms o similar to atherosclerotic degeneration; associated with proteolytic degradation & transmural loss of matrix, gross dilation (>50%) and rupture (confined to intima in athero) true aneurysm: dilation of all layers; can be fusiform (more common) or saccular pseudoaneurysm: contained rupture of vessel wall; very unstable o risk factors: cigarette smoking, HT, age >50, male, family Hx o infrarenal aorta>common iliac>femoral>popliteal aneurysms of ascending thoracic aorta rarely atherosclerotic in origin; cystic medial degeneration plays role, occurs in Marfan‟s Ehlers-Danlos, in response to HT and aging o Sx: none until rupture unless compressing neighboring structures; when ruptures, CV collapse, back/abd pain o Dx: PE, ultrasound or CT; arteriograms underestimate size, as thrombi not visualized o Outcome: determined by size: abdominal aorta: prone to rupture with size (100% in 5 years with 8 cm external diameter) popliteal: accumulate thrombus, eventually occlude o Treatment: aneurismal exclusion or bypass *Aortic Dissection o blood-filled channel divides the media, splitting intima and adventitia o arises from tear in intima that allows luminal blood to be driven into media; or rupture of vasa vasorum in adventitia o risks: anything that screws up normal integrity of elastic or muscular components of media chronic HT aging cystic medial degeneration (Marfan‟s, Ehlers-Danlos) trauma o most common in 60‟s-70‟s; men>women
o ascending thoracic aorta>descending thoracic>arch>abdominal type A: proximal, involves AA – can extend into arch or pericardium. More devastating, more common (2/3) type B: distal – confined to descending/abdominal o Sx: sudden, severe, ripping pain in anterior chest (A) or between scapulae (B); travels as dissection propagates; can occlude major branches, resulting in MI, stroke, loss of pulse in extremity (or difference in BP between arms); extends into aortic root, can disrupt valve and get aortic insufficiency; cardiac tamponade o Dx: transesophageal echo, MRI, contrast angio o Tx: arrest propagation; systolic BP, force of LV contraction ( blockers, vasodilators) early surgical correction in type A Medical for uncomplicated type B, surgery if propagating *Vasculitis o inflammation of vessel wall resulting from immune-complex deposition + complement activation, or cell-mediated attack o can cause end-organ ischemia because of vascular necrosis or local thrombosis o types: polyarteritis nodosa: systemic, small & medium arteries; PMN‟s infiltrate all 3 vessel layers. Idiopathic and in setting of Hep B Takayasu‟s arteritis: aorta & major branches – cerebrovascular ischemia, MI, arm claudication. Lose carotid, limb pulses Temporal arteritis/giant cell: medium & large arteries – cranial, aortic arch & branches. Rare. HA, claudication of jaw, visual impairment Thromboangiitis obliterans: medium arteries; distal vessels of extremities. Strong assoc with cigarettes. Distal arterial occlusion, Raynaud‟s phenomenon, migrating sup vein thrombophlebitis *Raynaud‟s phenomenon o vasospastic disease of digital arteries, results in tissue ischemia; occurs when susceptible people exposed to cool temps & emotional stress, possibly due to exaggerated reflex sympathetic tone (fingers have no 2 dilator fibers) o triphasic color response: blanch white as blood flow interrupted blue due to cyanosis, accum of desat Hb red as blood flow resumes o may have numbness, paresthesia, pain o Primary Raynaud‟s disease: isolated disorder, females>males o Secondary: component of CT diseases (scleroderma, SLE), arterial occlusive disorders, thoracic outlet syndrome o Tx: stay out of cold, wear gloves, CEB‟s, -1 blockers
Venous perforating vein Deep system Superficial system soleal sinus blood flow *Varicose veins o dilated superficial vessels, often develop in lower extremities. o Women>men; family Hx o saphenous vv & tributaries most common; also hemorrhoids, esophageal varicies, varicocele o results from intrinsic weakness of vessel wall, intraluminal pressure, congenital defect in valve structure/function valves play no role at rest; getting blood back to heart during exercise is dependent on valve closure, external muscle compression -> valve-muscle pump, counteracts hydrostatic pressure and limits edema formation o Primary: arise in superficial system risk factors: pregnancy, prolonged standing, obesity o Secondary: abnormality in deep system pushes blood superficially deep venous occlusion/insufficiency, incompetent perforating vv o Sx: dull ache after standing, swelling and skin ulceration near ankle; superficial thrombosis due to stasis, hematoma due to rupture o Tx: conservative: elevate legs, avoid prolonged standing, compression socks; injection of sclerosing solution; vein ligation and removal Deep Venous Thrombosis o occurs with decreased flow or stasis, local injury, hypercoagulable states (Virchow‟s tiad); tend to extend in direction of flow o most common in calves; also popliteal, femoral, iliac o risk factors: advanced age, surgery, trauma (esp after Fx of spine, pelvis, leg bones), prolonged bed rest, immobilization, previous Hx, genetic coag defect, pregnancy/OC‟s, malignancy o Sx: asymptomatic; claudication, unilateral leg swelling; localized warmth and erythema, tenderness over vein o Dx: duplex ultrasound, venogram, semilunar valve
o Tx: anticoagulation with heparin, coumadin o complications: pulmonary embolism – tend to originate from iliac, femoral, IVC; often fatal post-thrombotic venous insufficiency – ankle edema and ulceration, hyperpigmentation. Risk related to extent of valve destruction. Tx: maintain skin integrity, prevent edema with ext compression socks *Superficial thrombophlebitis: o much less serious than DVT; inflammation and thrombosis of superficial vein o erythema, tenderness, edema over vein o Tx: local heat, rest, NSAID‟s for pain o does not result in PE
Imaging Radiography Vascular Structures: Right border: superior vena cava ascending aorta right atrium inferior vena cava Left border: left subclavian artery aortic arch main pulmonary artery left auricle (atrial appendage) left ventricle
Lateral view anterior: arch & acscending aorta main pulmonary artery R & L pulmonary arteries right ventricle posterior: descending aorta left atrium left ventricle inferior vena cava
Chamber dilation: Volume overload valvular insufficiency e.g. aortic regurg
o aortic arch, LV, LA dilated; pulm edema w/Kerley B lines visible. Severe – can see RV dilation o volume is potent dilator, greater than high pressure Pressure overload valvular stenosis
e.g. rheumatic mitral stenosis
o more subtle; LA dilation visible as slight rounding of atrial appendage. o pressure overload is stimulus to hypertrophy (e.g. aortic stenosis); not seen on radiography
Pulmonary Vascular patterns caudalization: normal equalization: high output states e.g. anemia mild pulmonary venous hypertension e.g. mild LV failure left to right shunt e.g. atrial septal defect centralization: pulmonary arterial hypertension e.g. primary HT, chronic left-to-right shunt, chronic PE, chronic hypoxemia, pulm venous HT cephalization: severe pulmonary venous hypertension e.g. mitral stenosis, severe LV failure lateralization: poststenotic dilation of L pulmonary artery e.g. pulmonic stenosis - normal chamber size
Findings in heart failure: Acute: edema – Kerley B lines, haze, alveolar filling pleural effusion Chronic: Cardiomegaly enlarged lung vessels – equalization, rarely cephalization pleural effusion may be present Calcifications: Pericardium – due to viral & other pericarditis Coronary aa - atherosclerosis myocardium – remote infarction, rheumatic disease, aneruysm formation valves - degeneration, stenosis Echocardiography: High frequency waves reflected at interfaces between structures of differing acoustic impedance. Transesophageal and transthoracic, at rest and during stress. Good at distinguishing cardiomyopathies (dilated vs. hypertrophic vs. restrictive)
Views: parasternal long axis – LA, mitral valve, LV, aortic valve apical – four-chamber view; mitral, tricuspid, wall motion Doppler: evaluates blood flow direction, turbulence, velocity, estimation of pressure gradients pressure gradient = 4 X (velocity distal to stenosis) squared Catheterization: Measure pressures in heart chambers, determine CO & vascular resistance, examine structure and blood flow. Swan-Ganz catheter inserted into femoral, brachial or jugular vein; balloon inflated and floats back to heart; threaded through RA, RV to pulmonary arteries where balloon re-inflated to “wedge” into artery, measure pressures. RA = central venous pressure (can be estimated by JVD) since have no valves impeding venous return into RA. Normally = to RV pressure in diasole. o : intravascular volume depletion o : RV failure, R-sided valve disease, tamponade prominent a wave: tricuspid stenosis, RV hypertrophy prominent v wave: tricuspid regurg, RV failure RV o systolic pressure : pulmonic stenosis, pulmonary HT, RV failure o diastolic pressure : RV failure, tamponade, RV hypertrophy PA pressure; diastolic normally = LA pressure because pulm vasc is resistance o systolic & diastolic: pulmonary HT due to left CHF, lung dz, pulm vascular dz o systolic only: L to R shunt ( flow) PCWP = LA pressure = LV EDP (preload) o : left-sided CHF, mitral stenosis, tamponade
Can also measure CO using Fick: CO = O2 consumption/ arteriovenous O2 difference Calculate vascular resistance: SVR = MAP – RAP X 80 PVR= MPAP – LAP X 80 CO CO Nuclear Imaging: Can look for myocardial ischemia and infarction, hibernating myocardium, assess ventricular function by looking at uptake of various radiolabelled substances (e.g. FDGPET)
Arryhthmias -Impulse formation: automaticity; dependent on slope of phase 4 of action potential and threshold potential. Subject to autonomic modification: symp: Ih current, slope of phase 4 and threshold potential need to reach before upstroke – shorter AP para: Ih current, slope of phase 4 depol, threshold, prolongs K+ deactivation – longer AP, longer refractory period -Abnormal automaticity: myocardial cells outside conduction system acquire ability to spontaneously depolarize when become injured membranes become leaky; resting potential becomes less negative and gradual phase 4 depolarization is seen Escape: when SA node fails to spontaneously generate a rhythm or if generated impulse fails to conduct, see subsidiary pacemaker sites take over: junctional escape: 40-60 bpm ventricular escape: 30-40 bpm -Impulse conduction: impulses spread cell-to-cell in specialized conduction pathways and between muscle cells. AV node: 200 mm/sec His-purkinje: 4000 mm/sec atria/ventricles: 400 mm/sec -Conduction block: propagating impulse blocked when it encounters a region that is electrically unexcitable, either because the impulse encounters refractory or damaged cells; damage can be caused by ischemia, fibrosis, trauma. Drugs can excitability or refractory period. Removes normal overdrive suppression that keeps latent pacemakers in chek; see escape rhythms. AV blocks especially common. -Width of PR represents time it takes for impulse generated at SA to make it through Hispurkinje system to begin depolarizing ventricles. -Width of QRS represents time to completely depolarize ventricular muscle; widened (>.10 sec) when heart is depolarized by muscle-to-muscle conduction rather than via Hispurkinje system. -Re-entry: common in AV node, with bypass tract
lilly pg 243
Bradyarrhythmias: Treat with atropine, 1-agonists (isoproterenol), pacemakers Failure of impulse formation: o sinus bradycardia: all P‟s conduct, rate <60 due to high vagal tone, blockers, CEB‟s, hypothermia, hypothyroidism. Usually asymptomatic. o sinus pause: absence of P‟s & asystole for a while o sinus arrest: P‟s don‟t come back; escape rhythm kicks in, >3 sec o sick sinus syndrome/brady-tachy: periods of SA slowing follow a-flutter or a-fib. Failure of impulse conduction: o 1 AV block PR >.20; all P‟s conduct pg. 231
o 2 AV block o Mobitz I (WENCHEBACH!!!) progressive prolongation of PR interval before failure block at AV node pg 232
Mobitz II o abrupt failure of conduction of P‟s, without warning o block in distal conduction system; still have narrow QRS
pg 232
3 AV block no P‟s conduct; need all 3 features to diagnose o atrial rate > ventricular rate o loss of consistent relationship between P and QRS regular escape rhythm
pg 233
can occur at any level in conduction system; the more distal the block, the slower the escape
Intraventricular conduction defect: distal block in conduction system; depolarization can‟t take place via His-purkinje for affected side, must proceed by muscle-to-muscle conduction and thus produces QRS >.10 o RBBB: normally depolarizes RV, not seen on ECG because of smaller muscle mass. When blocked, RV depol occurs late, can now visualize depol on ECG. QRS ≥ .12 terminal S wave in I R‟ wave in V1 abnormal ventricular repolariaztion; get ST displacement, T wave polarity changes pg 235; Schwartz pg 246
o LBBB: depolarization must proceed down R bundle, then via muscle across IV septum from R to L. Terminal forces to left. QRS ≥ .12 prevents L to R septal activation: loss of septal Q‟s in I, aVL, V4-V6 initial - deflection in V1; initial + in I, L, V4-6 wide notched R in I, L, V5-V6 T‟s may be funky, as with RBBB
Schwartz pg 240
Ventricular pacemaker: get very vertical spike followed by wide QRS
Congenital Heart Disease Endocardial Cushion: Contribute to atrial & ventricular septa, mitral and tricuspid valves, annuli. Absent: primum ASD, VSD, cleft anterior mitral leaflet, cleft septal tricuspid leaflet, gap in annuli; not all parts of syndrome present in every patient. Division of Truncus: pg 241 s
Flow and development: if flow is limited or absent: hypoplasia or atresia downstream severe mitral stenosis -> hypoplastic left heart syndrome; hypoplasia of LV, aortic valve, ascending aorta depend on open tricuspid stenosis -> hypoplasia of RV, pulmonic valve, DA pulm trunk pulmonary stenosis: main pulm artery, RA hypoplastic as blood shunts L through foramen ovale; RV exposed to pressure load, becomes hypertrophic while exposed to less flow, so is smaller any form of aortic outflow obstruction may lead to ascending aortic and arch hypoplasia Fetal/Neonatal circulation lungs not inflated; oxygen gets to fetus from placenta via umbilical veins. About half shunts through ductus venosus to avoid liver. oxygenated blood is in right heart, preferentially crosses foramen ovale, goes to head systemic vascular resistance is low, pulmonary resistance is high; blood tends to shunt through ductus arteriosus to lower body in lieu of going through lungs at birth: o first breath -> PVR drops, blood flow to lungs increases o SVR increases; shunting through DA reverses direction, becomes L-> R
o venous return to LA closes foramen ovale a few days later, DA closes a few weeks later, ductus venosus obliterates over a year, DA obliterates over a few decades, foramen ovale obliterates…or not in 30-50% in twenties o risk for paradoxical emboli Lilly pg 330
Common Congenital heart lesions (See Anna‟s spreadsheet for clinical details) generally well tolerated in utero Acyanotic lesions Shunts: lesions result in left to right sided shunting o causes the pulmonary artery volume, pressure to -> pulmonary arteriolar hypertrophy, PVR -> pulmonary HT (Eisenmenger‟s syndrome); over time can reverse direction of shunt, cause right to left flow & Sx o isolated shunt defects prior to AV valves cause R sided dilation; lesions after AV valves cause L sided dilation (because get flow from LV into RV in systole with VSD, don‟t see RV enlargement) – see dilation where have diastolic volume overload o risks: endocarditis, pulmonary HT, heart failure, exercise tolerance Atrial septal defects – assoc with abnormal AV valves o ostium secundum: inadequate devo/overabsorption of septum primum o ostium primum: adjacent to AV valves o sinus venosus: sup portion of septum; often accompanied by anomalous drainage of R pulm vv into RA o flow through defect: function of size, compliance/diastolic filling of vents, PVR vs. SVR
o R sided volume overload, enlargement Ventricular septal defects o most commonly in membranous IV septum o small “restrictive” VSD: defect offers high resistance to flow, magnitude of shunt depends on size of hole (always L-> R) o large “non-restrictive” defect: shunt depends on PVR/SVR large L-> R shunt: pulm aa flow, LA venous return -> LA enlargement -> LV EDV -> initial in SV, over time can result in systolic dysfuntion can also result in Eisenmenger‟s syndrome Patent DA o magnitude of flow depends on size of ductus, PVR/SVR when PVR at birth and blood flows L to right to lungs -> flow to LA, LV, may have LV failure, Eisenmenger‟s sydrome with reversal of shunt -> desat blood to lower extremities, cyanosis
Non-shunt lesions: Aortic Stenosis o usually unicuspid/bicuspid o LV systolic pressure, hypertophy; dilation of proximal aortic wall Pulmonic Stenosis o at level of valve, within outflow of R ventricle or in pulm artery (as a result of hypoplasia) o RV pressure, hypertrophy; can have dilation of pulm artery with valvular Aortic coarctation o narrowing of aortic lumen pre-ductal: occurs proximal to ductus in embryo -> hypoplasia of aorta when DA closes, LV afterload, flow to descending aorta; may see differential cyanosis if DA remains open juxtaductal: most common, occurs at location of DA upon closure postductal: develops postnatally in LV afterload -> CHF. May compensate with LV hypertrophy, collateral circulation o blood flow to head, upper extremities is preserved; diminished to lower extremities Cyanotic lesions Right to left shunts: o cyanosis results from hypoxemia due to defects that allow poorly oxygenated blood from the R heart to be shunted to the L side, bypassing the lungs o risks: endocarditis, systemic emboli, polycythemia & hyperviscosity (body Hb to compensate for O2), exercise tolerance, hypoxemic spells
Tetralogy of Fallot o anterior displacement of infundibular septum -> unequal division of bulbus cordis VSD sub-valvular pulmonic stenosis – pushes blood through VSD, into: overriding aorta – receives blood from both vents RV hypertrophy Transposition of the great arteries o failure of AP septum to spiral; get two disconnected circuits o if DA, FO remain patent, can get some communication, maintain sufficient oxygenation
Nutrition and CV disease Risk factor LDL intervention that helps sat fat, trans fa, chol LDL R - phytoestrogens plant stanol/sterols omega-3 fa‟s bile acid absorption LDL oxidation HDL triglycerides homocysteine hypertension direct elevation omega-3 fa‟s fat intake, lose weight folic acid intake methionine intake BP SVR – vasodilation foods fruits, vegetables instead soy protein, yams Benecol, TakeControl fish, algae, marine plants soluble fiber – oats, fruit skins, metamucil antioxidants (theoretically) red wine, nuts, citrus booze (2 drinks/day) fish, algae, marine plants less junk, complex carbs green leafy veggies eat less meat less salt (hmm-controversial) plant protein has arg -> NO
Fatty acid nomenclature: Saturated. <10% daily calories, <7% on TLC Lauric acid (12C), myristic acid (14C), palmitic acid (16C) o plasma LDL - LDL R, clearance. HDL o found in cheese, butter, whole milk, coconut oil, palm oil Stearic acid 18:0 -> 18:1 converted by body to monounsaturated, effects on cholesterol. Found in meat, chocolate Monounsaturated 10-15% of daily calories o CIS: Oleic, erucic (22:1) – rapeseed, canola oil – palmitoleic (16:1) no effect on lipoproteins
o TRANS: elaidic acid (18:1) – margarine, shortening, French fries, baked goods. Act like sat fa‟s physiologically except HDL Polyunsaturated (omegas) – all essential. ≤ 10% of calories o Omega 6: linoleic (18:2) – linseed oil arachidonic (20:4) - seeds, nuts, grains slightly TG, oxidation susceptibility o Omega 3: linolenic (18:3) – walnuts Eicosapentanoic (EPA; 20:5) fish, algae, marine plants Docosahexanoic (DHA; 22:6) cardiac conduction system stability, TG, ox susceptibility
Cholesterol intake diet: 350 mg average, <200 mg on TLC effects on LDL are a function of LDL R activity; the lower the sat fa intake, the less the effect of dietary cholesterol Extreme fat restriction/substitution with carbs: endogenous sat, mono fa synthesis, recycling into TG TG - carbohydrate induction HDL net result: little/no cholesterol lowering below fat intake of 25% Exercise Responses to acute exercise HR ensures that CO metab MAP demand of pulse pressure skel mm is met in TPR metabolic vasodilator accum causes vasodilation in skel muscle; reflex sympathetic activity central command: raises set pt for baroreceptor regulation of MAP, but vasodilation causes fall below that level so still get large in sympathetic tone while get in MAP in sympathetic activity causes HR, M pg 186
contractility, venous & arteriolar tone get in cutaneous blood flow despite vasoconstriction; thermoregulatory reflexes override pressure reflexes coronary blood flow due to local vasodilation of coronary arterioles parasympathetic withdrawal - tonic level of activity (measure by looking at HR variability with inspiration) -> HR, EDV, ESV, SV due to diastole filling time need venous return – skeletal muscle and respiratory pumps. Both CO and venous return elevated without significant change in central venous pressure O2 to skeletal muscle o flow - CO 3-5X SV a little due to contractility HR 3.6 X o redistribute blood flow – divert from kidneys, gut (muscle goes from getting 20% CO at rest to 80% of increased CO) o extraction of O2 in exercising muscle 20% -> 80% more capillaries open due to vasodilation rightward shift of O2 dissociation curve w/ temp, pH Isometric exercise: o muscles squeeze BV‟s, TPR -> afterload -> cardiac work o get less HR, CO than with dynamic exercise; get more in diastolic, systolic, MAP.
Responses to chronic exercise – training effects VO2 max in capacity for cardiac work SV, MAP circulating BV HR at rest; no change in peak HR CO, EF at peak exercise (not at rest) cardiac enlargement -> EDV -> SV improved contractility augmentation of diastolic filling HRV - parasympathetic activity Aging and exercise: VO2 max – drops by 35% by 69 years HR response to exercise compared to young EF response to exercise compared to young o SV in young is achieved by ESV – relies on contractility o SV in elderly is achieved by EDV – tends to dilate diastolic function: changes present, even at rest o young: prominent early filling in diastole (passive) o elderly: less early filling, atrial filling (active) – suggests LV is stiffer aging heart responds less to adrenergic stimuli o amounts of circulating NE and epi
o due to: number of receptors (downregulation) changes in functional state of receptor also possible aging heart has parasympathetic activity o HRV; see less effect on HR with atropine o suggests numbers of mAChR‟s as well
Congestive Heart Failure = failure of heart to pump sufficient blood and O2 to meet the metabolic demands of the body, or to do so only at abnormally elevated filling pressures. a common, final pathway for a wide variety of disease states Pathophysiology Systolic dysfunction: most common type o diminished capacity to eject blood from the affected ventricle - EF; maintain SV for a while (until decompensated) Left sided: impaired contractility – MI, chronic volume overload (mitral/aortic regurg), dilated cardiomyopathy o # 1 receptors, uncoupling from adenyl cyclase o abnormal Ca++ homeostasis – lower peak release, impaired reuptake ( levels mRNA for SERCA) o hypothesis: may result from apoptosis of myocytes, maybe due to wall tension post-infarct remodeling LV can volume 4.5X in end-stage failure changes from conical to spherical shape interstitial fibrosis pressure overload - resistance to flow – aortic stenosis, HT pressure-volume loop: ESV, EDV, EF Lilly pg 202
LV pressure transmited to LA, then to pulm vv and caps. Get pulmonary congestion and edema Right sided: RV is thin walled, highly compliant – can accept a wide range of volumes. Susceptible to failure with sudden
increase in afterload – e.g. PE, advanced pulmonary disease (cor pulmonale) most common cause is left-sided heart failure diastolic pressure transmitted to RA, subsequent congestion of systemic vv RV output can result in LV filling, fall in LV SV and CO Non-cardiac causes include severe anemia, metabolic demand
Diastolic dysfunction – ventricular filling takes place at elevated pressures due to reduced chamber compliance. Often present with vascular congestion impaired early diastolic relaxation increased stiffness of ventricular wall pressure volume loop: EDP Lilly pg 202
Adaptive mechanisms Lilly pg 205, syllabus 302
in acute failure, mechanisms are adaptive: o symp: contractility & vasoconstriction o renin/ATII/aldost: retention of Na+ and H2O, preload vasoconstriction -> maintain arterial BP & vital organ perfusion (redistribution) ADH secretion -> preload o other mechanisms: endothelin (vasoconstrictor), TNF- in chronic failure, mechanisms are maladaptive o vasoconstriction afterload, worsens SV and forward CO o HR also metabolic demand of heart, may cause angina o symp: catecholamines are mitogenic; myocyte & smooth muscle cell growth, collagen deposition. Continued stimulatin -> downregulation of receptors, contractility o RAA system: myocardial collagen deposition -> fibrosis blood volume worsens pulmonary edema o get ANP, BNP in attempt to balance vasoconstriction/vasodilation o overall, heart becomes less preload dependent; for a given in preload, get less of an in CO. Becomes more dependent on afterload; if afterload for these patients, get a lot of “bang for your buck”
Cardiac Index = CO/body surface area normal: 2.5 – 4.5 Classification: NYHA: class I: asymptomatic class II: symptomatic with moderate activity class III: symptomatic with mild activity class IV: symptomatic at rest Alternative: stage A: at high risk but without structural disease or Sx – pts with HT, CAD, DM o Tx: treat HT, quit smoking, treat dyslipidemia, alcohol abuse; ACE I‟s in some stage B: structural heart disease without Sx - pts with MI, EF, asymp valve dz o Tx: stage A + ACEI‟s, blockers in appropriate pts stage C: structural heart disease with prior/current Sx – SOB, fatigue, exercise tolerance o Tx: stage A + diuretics, ACEI‟s, blockers, digitalis, salt restriction stage D: refractory heart failure – pts with Sx at rest despite medical therapy o LVAD‟s, heart transplantation, IV inotropes (dobutamine)
Symptoms & Signs of heart failure Symptoms L sided: Cardiac signs displaced PMI S3 gallop accentuated P2 MR – holosystolic murmur tachypnea pulmonary rales cold, mottled extremities tachycardia low systolic BP pulse pressure
pulmonary vascular congestion exertional/rest dyspnea cough, orthopnea, PND low cardiac output fatigue, weakness, confusion, anxiety, anorexia
R sided: systemic venous congestion dependent edema, abdominal bloating pleural effusion anorexia, nausea, RUQ abdominal pain dependent edema nutmeg liver hepatomegally, ascites
Lab findings: Get ECG & echo on everyone; catheterize if need biopsy, tough Dx ECG: tachycardia, bundle branch block, chamber enlargement, arrhythmias, ischemia/infarction CXR: cardiomegaly, pulmonary congestion, pleural effusions Blood: hyponatremia (bad sign), RBC sedimentation rate, BNP o cardiomegaly – thyroid abnormalities, Fe storage abnormalities Prognosis: worse with CAD, class IV, S3, high plasma NE, renin, ADH, BNP, hypokalemia, hyponatremeia worse with frequent PVC‟s, ventricular arrhythmias or tachycardia, A-fib or Aflutter Treatment: (I figure if I write this down enough times, it simply has to stick eventually) Vasodilators ACE inhibitors: vasodilators, afterload o Sx and survival o incomplete suppression of AT II AT II antagonists o complete suppression of AT II
o doesn‟t make „em cough Nonspecific vasodilators – isosorbide dinitrate + hydralazine ( preload and afterload, respectively) o more potent than ACEI‟s o less effect on survival Diuretics Loop – use with Sx of volume overload; no effect on survival or cardiac performance in normal dosing range spironolactone: o class III & IV, for pts with hypokalemia on loop diuretics o does survival Digitalis contractility by blocking Na/K ATPase, Ca++ improves Sx, no survival benefit blockers systolic function, survival, symptoms start low, go slow, aim high – negative inotropes at outset PDE inhibitors – milrinone increases Ca++ concentration – inhibits cAMP degradation improves class IV Sx, but negative impact on survival (arrhythmogenic, cardiotoxic) Adrenergic agents – dobutabmine increases Ca++ concentration improves class IV Sx, negative impact on survival; can‟t use with blockers Surgical treatment o revascularization for ischemic etiologies, early on o valve surgery for stenosis/regurg; repair if possible o pacemakers for bradyarrhythmias, tachys in conjunction with AV ablation; atrial synchronous biventricular pacing, bilead pacing in both ventricles for widened QRS o modify shape/size with cardomyoplasy, ventricular reduction (sort of a heart tuck?) o LVAD‟s for short term, as bridge to transplantation; get recovery of contractile function and adrenergic response, does reduce mortality, so maybe destination therapy as well o transplantation for class IV, expected survival < 12 months
Cardiomyopathies – primary diseases of the myocardium Dilated: ventricular dilation with systolic contractile dysfunction most common type; incidence is increasing, more common in African descent, in males etiologies
o inflammatory: infectious or non-infectious (viral – Cocksackie B, echovirus)
o
o o
o
metabolic: nutritional endocrine altered metabolism electrolyte imbalance toxic EtOH, cocaine, catecholamines antineoplastics - anthracyclines genetic – mutation in actin, desmin as well as: Duchenne Friedreich‟s ataxia Kearns-Sayre syndrome miscellaneous postpartum – last trimester, 1st 6 mo postpartum. Half recover. obesity heat stroke, hypothermia radiation tachycardia idiopathic – majority of cases
Pathology o chamber dilation; ventricles > atria; contractile function heart tries to compensate for impaired contractility with FrankStarling mechanism, neurohormonal activation -> HR, contractility, SVR to buffer fall in CO o variable hypertrophy o thrombi frequently present -> anticoagulation o regurgitation as mitral/tricuspid valves fail -> atria dilate, further forward SV gross: flabby heart, four chamber dilation. micro: hypertrophy, interstitial fibrosis, low level chronic inflammatory infiltrate Clinical Manifestations o congestive Sx, low CO Sx and signs – S3. Tx for heart failure. prognosis: variable; spontaneous improvement in up to 25%; with Sx, 50% mortality at 5 years
Hypertrophic: myocardial hypertrophy in the absence of a stimulus to hypertrophy. Vigorous systolic LV contraction but impaired relaxation and filling, high diastolic pressures etiologies o familial (auto dominant, variable penetrance) 50% mutation in -myosin heavy chain most common; also troponins I & T, tropomyosin, light chains. Give rise to poison polypeptide o sporadic pathophysiology o marked in mass, small ventricular cavities; reduced compliance and diminished ventricular filling -> diastolic dysfunction
o obstruction of LV outflow due to excess muscle mass, abnormal motion of anterior mitral leaflet o high propensity for arrhythmias and death o gross: very thick LV wall; if asymmetric, tends to be septum o micro: myofiber disarray, myocyte hypertrophy Signs and symptoms: o LV lift o prominent S4 o systolic murmur with outflow tract obstruction, some with MR o LV EDP, LA pressure, pulmonary congestion o Sx without outflow obstruction: dyspnea with exertion with outflow obstruction: even higher LA, pulm pressures; wall stress, O2 consumption -> angina; syncope ECG: ST, T wave abnormalities massive voltages prominent Q waves due to thickened septum
Schwartz pg 307
Prognosis o natural Hx: long period of stability, some progress to LV dilation, sudden cardiac death esp with septal hypertrophy, family Hx of sudden death, early age of onset Tx: blockers, CEB‟s -> negative inotropes diuretics for volume overload Sx surgical options: myomectomy
Restrictive Cardiomyopathy: least common type; increased myocardial stiffness without hypertrophy, leading to impaired relaxation and poor diastolic filling. etiologies: o interstitial infiltration by amyloid (women>men), cancer, sarcoidosis o congenital endomyocardial fibrosis o metabolic storage diseases hemochromatosis, glycogenoses, mucopolysaccharidoses
o interstitial fibrosis o differential: constrictive pericarditis signs and symptoms: o mostly due to low CO: exercise intolerance, weakness, exertional angina o some congestive Sx – dyspnea, JVD, hepatomegaly, ascites, edema Dx with catheterization, CT, MRI, Bx Tx: none except hemochromatosis; poor prognosis
Pericardial Disease Acute Pericarditis: inflammation of layers of pericardium. Pretty common. etiologies: o idiopathic/viral – echovirus, cocksackie B o uremia – complication of chronic renal failure o bacterial infection – G+ more often; fulminant, rare o acute MI o TB o trauma o neoplastic – metastatic spread of lung, breast, lymphoma cancer o radiation induced pathology o PMN infiltrates, enhanced vascularity, fibrin deposition, fluid exudation Signs and Sx o chest pain – retrosternal, knife like, positional, rads to trapezius (vs. MI) o dyspnea o pericardial rub on auscultation – sandpaper like, waxes and wanes ECG: o ST is concave upwards (vs convex upwards in MI) o ST changes widespread – all/most leads o ST elevation returns to baseline prior to T wave inversion o see T wave inversion without loss of R or new Q o can see sinus tachy; atrial/ventricular arrhythmias uncommon Schwartz pg 94
usually self limiting; Tx is rest, analgesia, oral corticosteroids in severe/recurrent cases, anticoagulants for post-MI pericarditis, antibiotics and drainage for purulent forms
Pericardial Effusion: silent unless pressure increases sufficiently to compress heart, interfere with diastolic filling intrapericardial pressure rise is related to Lilly pg 294 volume of fluid, rate of accumulation, characteristics of pericardium without tamponade, Sx: o dysphagia o cough from tracheal compression o dyspnea o hiccups from compress. phrenic n o hoarse from compress. recur laryngeal n PE: muffled heart sounds, dullness below L scapula due to compression of lung base (Ewart‟s sign); rales due to compression of lung parynchyma Echo: small effusion -> fluid posterior large effusion -> fluid anterior Pericardial Tamponade: fluid accumulates under high pressure, compresses cardiac chambers and severely limits filling. SV, CO leading to hypotensive shock and death etiology: o any etiology of acute pericarditis can do it; most common are neoplastic and uremic clinical manifestations: o elevated JVP o pulsus paradoxus – drop of >10 mm Hg in systolic BP on inspriration o tachypnea o tachycardia o hypotension Echo: RV/RA diastolic collapse, swinging heart, fat IVC cath: y descent is blunted as ventricular filling is impaired (Lilly 299) Tx: Pericardiocentesis; recurrence in 20%. Pericardectomy
Constrictive pericarditis: complication of pericardial disease; rigid pericardium interferes with diastolic filling etiology o any etiology of acute pericarditis; TB used to be most common cause pathology o following acute effusion, fluid is organized with subsequent fusion of layers of pericardium, scar formation o virtually all filling of the ventricle occurs in early diastole RV expands, quickly reaches its limit -> venous return ceases -> signs of R heart failure impaired filling of LV -> SV, CO, BP -> fatigue, weakness signs o JVP, hepatomegaly o pulmonary venous congestion o Kassmaul‟s sign: paradoxic in JVP with inspiration o low QRS voltage on ECG Cath: o exaggerated y descent o elevation, near equilibration of diastolic pressures o dip and plateau configuration of early RV and LV tracings
Lilly pg 299, 301
Tx: pericardiectomy Circulatory Shock: generalized severe reduction in blood supply to tissues; CO; blood pressure is usually low (not always). Cardiogenic: pumping ability is compromised o MI, myocarditis, cardiomyopathy, acute valve dysfunction, tamponade, refractory arrhythmias Underfilled vasculature o inadequate volume: hypovolemic shock hemorrhage, severe diarrhea, burns, prolonged vomiting o expanded vascular space anaphylactic shock – severe allergic rxn -> vasodilation septic shock – endotoxin induces NO synthase -> vasodilation neurogenic shock - symp outflow -> vasodilation
Compensatory mechanisms: M pg 194
Decompensation: vasoconstriction decreases flow to heart, liver, kidney spiral develops: lactic acidosis, myocardial depression, electrolyte imbalance, reduced sympathetic drive -> progressive myocardial dysfunction, vasodilation -> death M pg 196
Signs and symptoms: o poor cerebral perfusion: dizziness, confusion, agitation, unconscious o low blood pressure o tachycardia, tachypnea o oliguria due to poor kidney perfusion Diagnosis: telling etiologies apart using R heart cath PCWP CO SVR Tx Cardiogenic inotropes, afterload balloon counterpuls. Hypovolemic volume replacement Sepsis volume, vasoconstriction, antibiotics Balloon Counterpulsation: put balloon into descending aorta; inflates during diastole to coronary perfusion, deflates during systole to afterload.