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FISHMAN’S MEDICINE
Chapter 1 – Sudden Death
Sudden Death
• Unconscious
• Apnic
• Without Blood Pressure
• Unexpected
• Non traumatic
• Instantaneous
• 300,000 per year
MechanismsSmallest Percentage
Respiratory failure Neurologic (subarachnoid hemorrhage)
Largest Percentages are:
Cardiovascular – 4 mechanisms
1. Arrhythmiasa. Mostly Ventricular tachycardia evolving to ventricular fibrillation b. Bradycardias
i. Sinus – e-
discharge at sinus node < 60BPMii. Junctional
c. Ideoventricular Rhythmi. An independent cardiac rhythm caused by a repeated
discharge,
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iii. Aortic Dissectioniv. Massive Pulmonary Embolism
3. Electromagnetic Dissociation – Presence of electrocardiographic activity without a detectable blood pressure
a. Can occur with
i. Global myocardial Ischemiaii. Infarct b. May be secondary to mechanical obstruction
i. Pericardial Tamponadeii. Tension pneumothorax – Interplueral air from lungs that can’t
escape from the pleural linings.
iii. Cardiac ruptureiv. Papillary muscle rupturev. Aortic Stenosis (critical) – Stricture of aortic valve decreasing
cardiac output increasing peripheral vascular congestion
vi. Pulmonary embolus
4. Vasopressor Deatha. Inappropriate reflex decrease of HR, contractility & peripheral vasculartone
b. Results in precipitous hypotensionc. Triggered by receptors in Coronary Sinus (venous channel in coronary
sulcus that drains 5 veins) and base of heart
d. May be involved in deaths from a hypersensitive carotid sinus baroreflexor pulmonary thromboembolism
Epidemiology
90% of sudden death associated with coronary artery disease
30% new MI
50% acutely ruptured plaque
Most have history o f MI or angina
Many have had chest pain/dypsnea 1 month prior
Risk factors
HypertensionSmoking
Diabetes MellitusHypercholesterolemia
Younger persons wi th congenital heart disease
Hypertrophic cardiomyopathySmall or anomalous coronary arteries
Congenital aortic stenosis
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Heritable disorders
Long QT syndrome – inherited prolonged QT interval associated with ventricular
tachycardia, cardiac arrhythmias, syncope & sudden deathMutations in Seven Genes
Encode Ion channels
No Disease
Drugs
Cocaine & ephedrineSevere psychological or emotional stresses
Prevention
Many present with vague, ill defined symptoms shortly before death
Long term outlook is grimCPR teaching with sophisticated ambulance teams – Resuscitation ~ 40%
Identification of Risk Groups
Young healthy athletes with structural lesions or family history of sudden death
Beta blockers for all s/p MI unless cont raindication
Patient resuscitated out of hospital from Heart Attack not precipitated by MIResultant from
Heat block
Bradycardia
Supraventricular
arrhythmiasRapid atrial fibrillation
Patient with conductive bypass tractsWolf-Parkinson-White – Dual paths of conduction short cut to ventricle
Prolonged QT
24hr ECG may reveal problems, but can’t be used to effectively selectantiarrhythmic routine
Better is intracardiac Electrophysiologic (EP) studies
Heart put through programmed rhythms
Arrhythmias identified
Different meds tested to see if arrhythmias are stoppedInvasive
Expensive
Screen for st ructural heart d isease
Stress testing with ECG
Ventricular ectopy alone does not warrant treatment
Symptoms of Ectopy
Palpations, dizziness, syncope
No evidence on routine ECG
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Monitor as outpatients
Documented ventricular tachycardia therapy
EP guided antiarrhythmics
Empiric use of Amioderone
Implantation of Automatic Implantable Cardioverter Defibrilator (AICD)
AICD increases survival in
Previous MI
Impaired Left ventriculoar
functioin
Non-sustained ventricular
tachycardia
Inducible ventricular tachycardiaat EP studies
Multicenter Automatic Defibri llator Implantation Trial (MADIT) andMulticenter Unsustained Tachycardia Trail (MUSTT)
Overall mortality decreased 50% with AICDs
Coronary Artery bypass graft (CABG) – Patch trial
Implantation of AICD at time of bypass sxPatient with abnormal signal-averaged ECG
Reduced antiarrhythmic deaths 45%
No significance in overall mortality
MADIT II stopped
30% decrease in mortality with AICD No arrhythimic criteria
Included patients with post MI with left vientricular impaiment
Vasopressor syncope
Head up testingHead up tilt ~60 Degrees precipitates symptomatic hypotension or syncope
CPR
CPR is victim’s best chance
Every minute lost equates to a 7-10% decrease in survival rate
Airway cleared
Head extendedMouth to mouth
If AED available, use immediately
If no AEDBrisk chest thump may defibrillate ventricular fibrillationTry only once
80-100 compressions per minute
At no time other than AED should CPR stop
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Arrival at ED
1. Immediate attempt at cardioversion2. Intubate & ventilate with O2 supplemented air3. Central Line4. Electrical conversion, Lidocaine, Procainamide, Bretylium
5. EP & more electroconversion
Treatment of Bradycardia, heart b lock & asystole
Atropine Blocks vagal parasympatheticsCauses tachycardia
Isoproterenol & epinephrine
Stimulate beta adrenergic receptorsPowerful Inotropic & Chronotropic
Beta blockers relax smooth muscle, decreasing peripheral resistance
Should not be used as sole agents to reverse hypotension
Persistent hypotension wi th suffic ient pulse rate Norepinephrine
Alpha stimulator
Vasoconstriction
DopamineStimulates Alpha & Beta receptors
Low dose stimulates cardiac contractility with less vasoconstriction than
norepinephrineHelps protect sensitive vascular beds like kidneys
Severe Acidosis
Sodium Bicarb to treatDose according to arterial Ph & pCO2
Signs & SymptomsHeadache
Dypsnea
Fine Tremors
TachycardiaHypertension
Vasodilitation
May result in if overdose:Respiratory acidosis
Increased pCO2 Excess carbonic acidIncrease plasma H
+ concentrations
Caused by
Decreased alveolar ventilation or suppression of respiratoryreflexes
Increases CO2 combines with water forming carbonic acid that
leads to a decrease in blood pH
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Chapter 2 – Coronary Artery Disease (incomplete)
Angina Pectoris
Distinct variety of heart pain
Myocardium is starved of O2 & nutrients
Inadequate coronary circulationMost common cause is progressive narrowing of coronary arteries by
atherosclerotic plaques
Lesions are composed of
Intimal foam cells (Macrophages)Disorganized medial cells
Surrounded by interstitium filled with cholesterol
Symptoms don’t occur until >75% of lumina is occluded
Reduced blood flow can lead to
Akinetic (non-contractile)
Dyskinetic (Bulges when the rest of the heart contracts)Alteration of ST segment & T waves
Abnormalities of cell membrane pumps
Altered ionic permeabilityIncrease of lactate leaving the heart from anaerobic metabolism
Frequency & Intensity
Do not indicate severity of Coronary Artery Disease (CAD)
Degree of vascular obst ruction correlates closely to risk of death
Coronary Vasculature
3 Major Arteries
Right Coronary Artery (RCA)
Left Anterior Descending Artery (LAD)
Left Circumflex Artery (LCx)In General Left system supplies the Anterior
& lateral of the left ventric
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Two coronary ostia
Located just above aortic valve
1 to RCA
90% of people this supplies blood to the AV node as well as posterior &
inferior regions of left ventricle1 to Left main Coronary Artery
Divides into
LAD & LCx (10% LCx supplies AV node and posterior of left ventricle)
In General Left system suppl ies the Anterior & lateral of the leftventricle the Right system supplies the Right ventric le, AV node &inferior & posterior walls of the left ventricle.
Diagnosis & Clinical Manifestations
Often clear from the characteristic symptoms & physical findingsConfirmed byECG changes during episodes of pain
TNG ameliorates pain
Atypical land ECG nonspecific pain does not ru le out CAD
Exercise tests
Radionucleotide scansAngiography
These tests do not correlate pain to angina, but only if the person has CAD
Signs & SymptomsSqueezingPressure
Levine Sign – Clenched fist over heart
Relieved by TNG
Risk factors
SmokingFamily hx of premature atherosclerosis
Hypertension
DiabetesHypercholesterolemia
Low in women until menopause
During Angina
Reflex hemodynamic changes
HypertensionTachycardia
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Ischemia of Left Ventricle
S4 Gallop may occur
Abnormal S2 splitting may occurECG may reveal
ST depression
T-wave inversion
With out Angina
Physical exam usually normalIschemic episodes may occur without pain
Differential Diagnosis
1. Hyperventilation Syndromea. Sharp Chest Pain b. Tingling fingersc. Lightheadedness
d. T-wave inversion on ECG is common2. Tietze’s Syndrome
a. Arthritis of chest wall b. Pain can be reproduced by pressure over offending jointc. Relieved by aspirin or other anti-inflammatory agent
3. Reflux esophagitisa. When laying flat b. Esophageal spasm may cause pain after mealc. Sometimes relieved by TNG
4. Aortic Dissectiona. Aortic intima tear
b. Ripping pain can be projected to back & abdomenc. Dissection may occlude vessels or cause aortic insufficiencyd. Chest x-ray may reveal widened aortic shadow
Other conditions that may cause chest pain areDiseases of the lung like pulmonary embolism
Abdominal issues – peptic ulcer, choleocystitis (may have inverted T-waves) etc
Diagnostic Tests
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Chapter 3 – Cardiac Catheterization and HemodynamicMeasurement
Introduced by Werner Forssman – 1929 – Tied assistant down
Applications of
Catheterization of the right heart chambers and pulmonary circulation is
performed routinely in many ICU to monitor cardiac functionCatheterization of the left ventricle & coronary arteries is performed in special
labs prior to cardiac Sx & Coronary angioplasty
Right Sided Heart Catheterization
A pulmonary arterial (Swan-Ganz) catheter can be introduced into any large peripheralvein.
Maneuvered intoVenae Cavae
Right AtriumRight Ventricle
Pulmonary Artery
Pressures measured during insertion or removal of the catheter:Pulmonary artery
Right Ventricle
Right atriumPulmonary Capillary Wedge Pressure (PCWP)
Balloon floated from R ventricle to wedge in small pulmonary artery
Measures left atrial pressure indirectly – Once a pulmonary artery isoccluded, the distal of the balloon measures the pressure of the left atrium.
High PCWP = Cardiogenic Pulmonary edema
Low PCWP = hypovolemia
Indications for the Swan-Ganz
1. Resolution of any uncertainty about filling pressure of Left ventricle –especially hypotensive patients
a. Compromised Left Ventricle who require high filling pressure, butclose to pulmonary edema
b. Patients in shock
c. Large myocardial infarctd. Patients with heart & lung disease to determine source of
pulmonary edema, i.e. the heart or the lungs.2. To measure cardiac output
a. Cold water, dye or a solution injected b. Predicts stroke volume, and cardiac output (SV for 1 minute)c. Cardiac Index
i. Cardiac output divided by body surface area
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ii. Normal is 2.5-4.2 L/min/m2 iii. Less than 1.8 implies cardiogenic shock
3. Measure pressures in the right ventriclesa. Evaluate severity of pulmonary hypertension b. Pericardial disease can be evaluated by pressure contour from right
ventricle4. To evaluate left-to-right shuntsa. Measure O2 sats from different areas of the heart b. Right atria & ventricle usually the same
Complications
Not unusualBalloon tip stuck in wedge pulmonary infarct
Pulmonary artery perforation by tip
Life threatening hemorrhage
Hemoptysis
KinkingLocal infection
ThrombosisVentricular ectopy or right bundle branch block as catheter passes through right
ventricle
Left-Sided Heart Catheterization
Brachial or Femoral ArteryPressure measurements
Injection of dye
Prep for CABG & PTCA dye into coronary arteries
Indications
1. Diagnostic Coronary Angiographya. Assess degree of blockages b. Determine health of CABG
2. Left Ventriculographya. Dye in left ventricle
i. Cineangiography – analyses wall motion & abnormalitiesii. Calculated ejection fraction
iii. Reveals presence of1. aneurysms
2. Intracardiac masses3. Thrombi4. Mitral regurgitation
b. Dye in Aortic Rooti. Regurgitiation
ii. Aortic aneurismiii. Aortic dissection
3. To measure pressures
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a. Important ini. Mitral stenosis
ii. Aortic stenosis4. Perform Therapeutic Percutaneous Coronary interventions
a. PTCA (Percutaneous Transluminal Coronary Angioplasty)
b. Stent placementc. Valvuloplasty (usually mitral valve)d. Repair of congenital defecte. Atrial septal defects
Complications
Vascular damage at insertion siteArterial thromboembolism
Dye anaphylaxis
Myocardial infarction
Stroke
DeathComplications should not exceed 1%
Transient hypotension or arrhythmias commonly resultDye may cause intravascular expansion & pulmonary edema
Contrast induced renal failure
Important to monitor urine output of dye
Peripheral Arterial and Central Venous Catheterizations
Radial artery
Continuous monitoring of arterial blood pressure
Access for ABGs
Preferable to repeated arterial puncturesComplications are rare, but include
Exsanguination
Local vasospasmThrombosis with ischemia
Pain
Distal tissue necrosisExternal Jugular Vein
Referred to as Central Venous Line or Central Line
Stable access for IV infusion
Patients that depend on constant infusion
Meds that are to irritating e.g. catecholaminesCan not determine left ventricular function
Complications arePneumothorax
Hemorrhage
Venous thrombosis
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Chapter 4 – Valvular Heart Disease
The most important consideration is timing of surgery
Not every patient with valvular disease requires surgery, but if an opportunity
presents, it should be taken. Normal valve is diaphanous & wispy.
Two forms of Valvular Disease.1. Incompetent or regurgitant valves
a. Ruptured chordae tendonae b. Valve ring loosened by dissecting blood or pusc. Torn or distorted
2. Stenotic valvesa. Scaring or Congenital
Evaluation of Valvular Heart Disease
Initial evaluation involves five essential areas1. History
a. Prior rheumatic heart disease b. Heart failurec. Endocarditis angina syncope
2. Physical Examinationa. Careful auscultation for clicks or murmurs b. Palpate precordium for atrial or ventricular hypertrophyc. Inspect neck veins for distentiond. Right atrial pressuree. Detect abnormalities of wave form suggestive of tricuspid regurgitation
3. Chest X-Raya. Look for chamber enlargement b. Valve calcificationc. Pulmonary edema
4. Electrocardiogram (ECG)a. Evaluated for evidence of chamber hypertrophy & arrhythmias b. Echocardiographyc. Non-invasive visualization of heart & valves
5. Echocardiographya. Transthoracic echocardiography is non-invasive & painless b. Imaging of
i. Structures of the heartii. Valves
iii. Evaluate blood flow2-D echocardiography gives real-time view
Quantified flow by Doppler ultrasonographyTransesophageal Echocardiography (TEE)
Minimally invasive
Probe advanced down esophagus
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Greater sensitivity for
Atrial thrombi
Valvular vegetationsProsthetic valve dysfunction
Itraoperative use to guide cardiac surgery
Normal Cardiac Cycle
Onset of left ventricular systole
Left ventricle contractsPressures in the ventricular chamber riseMitral valve closes
Produces the first heart soundS1
When left ventricular pressure exceeds Aortic pressure
Aortic valve opens
Left Ventricle & aorta have equal pressures during ventricular emptying
When aortic pressure exceeds ventricular pressureValve shuts
Produces S2 Two components to S2 sound
Aortic valve closure (A2)
Pulmonic valve closure (P2)During inspiration, A2 & P2 move slightly apart (normal splitting)
Result of increased venous return to right ventricle and delayed closure of
pulmonic valve
When declining left ventricular pressure drops below the pressure in the leftatrium, the mitral valve opens & the left atrium & ventricle have equal pressure
Heart Murmurs
Character, location, intensity & direction of radiation may be clues to the severity
During systole,Aortic & pulmonary valves are open
Mitral & tricuspid valves are closed
Systolic murmursResult from stenosis of aortic or pulmonic valves
Incompetence of mitral or tricuspid valves
During Diastole
Aortic & pulmonic valves are closed
Mitral & tricuspid valves are openDiastolic murmurs suggest incompetence of aortic or pulmonic valves
Stenosis of the mitral & tricuspid valvesMurmurs usually radiate along the direction of the jet underlying them
i.e. mitral regurgitation radiates towards axilla
Aortic stenosis radiates towards neck
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Mitral Stenosis
Hemodynamic Consequences and Natural History
Rheumatic Heart disease accounts for most cases
Lesion runs a leisurely course
Initial symptoms delayed 15-20yrs Narrowing of mitral orifice
Pressure in Left Atrium Rise Needed to maintain flow from Left Atrium to Left Ventricle
Left atrium enlarges
Pulmonary venous & pulmonary capillary pressures rise (Sometimes with pulmonary edema)
Early in course of mitral stenosis
Shortness of breath
Only during strenuous exerciseLater in course
Symptoms even at restLaying flat makes worse7 years from onset to complete incapacity
Advanced mitral stenosis
Two mitral cusps become adherent at the lateral bordersFrom 4-6 down to 1cm
2
Surrounded by calcium deposits
When left atrial pressures rise to ~25mmHgPulmonary edema
Dypsnea
Orthopnea
May become high enough to cause right ventricular failureMay appear to be a grace period
Pulmonary edema cease (Right ventricle can’t overload left side)
Tricuspid regurgitation may appearDamage may be too great for surgical intervention to benefit
Oddities
10-15% of patients with mitral stenosis follow different course
Initial stagesPulmonary vasculature constricts early
Consequent cor pulmonale
Right ventricular failure
Less pulmonary edemaSymptoms & Complications of Mitral Stenosis include:
1. Dyspnea, orthopnea & attacks of frank pulmonary edemaa. Often induced by
i. Exerciseii. Pregnancy
b. Uncontrolled atrial fibrillationc. Tachycardia is poorly tolerated
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i. Reduces the time available for the left atrium to empty (i.e.,diastolic filling time)
2. Hemoptysis can occur in a variety of formsa. Pulmonary apoplexy
i. Frank blood is suddenly expectorated
ii. Rupture of bronchial veins b. Pink frothy sputumi. Pulmonary edema
c. Blood-tinged sputumi. Infectious bronchitis
ii. Pneumoniaiii. Upper & lower pulmonary infections
3. Fatiguea. Prominent symptom in later stages b. Reflects low-output state
4. Systemic & pulmonary embolization
a. Commoni. Atrial fibrillation patientsCourse of Mitral stenosis may be interrupted with bouts of pulmonary edema
Patients who become pregnantSuffer bronchitis
Atrial fibrillation
Initially sporaticAdvances to chronic
Contributes to pulmonary or systemic embolization
Early death may occurPulmonary edema or emboli
Patient endures progressive increments in left atrial & pulmonary arterial
pressuresSymptoms of right ventricular failure become apparent
Physical findings
Mitral facies
Malar flush
Cyanosis of lipsDiastolic murmur of mitral stenosis has several characteristics
1. S1 is accentuateda. Valve is wide open at onset of ventricular contraction
i. Result of elevated left atrial pressure b. Snaps shut over wider excursion than normalc. May be the only ausculatory clue to early mitral
2. Opening snap of stenosed mitral valvea. Early in diastole b. Short high-pitched sound following S2 c. Distinguish from
i. Widely split S2 from respirations
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ii. Loud S3d. Interval between S2 and opening snap
i. Reflects abnormal pressure gradient across valvee. As stenosis worsens
i. Atrial pressure rises
ii. Valve opens progressively earlier in diastoleiii. Opening snap moves closer to S2 3. Mid diastolic rumble
a. Result of turbulent flow across valve b. Low pitchedc. Localized to cardiac apexd. Best detected using the belle. Patient in left lateral decubitus
4. In many patients presystolic accentuation of murmur immediately precedes S1 a. Produced by augmentation of flow during left atrial contraction b. Usually lost when fibrillation develops
Diagnostic tests
Chest X-RayMay show large left atrium
Straightening of left-sided heart border
Widening of carinal angleDisplacement of the esophagus on lateral view
May be evidence of pulmonary edema
Late in the disease
Right ventricular enlargementECG
Large biphasic P waveSuggestive of left atrial enlargementDoes not show if atrial fibrillation is present
2-D echocardiography
Stenotic valve can be directly visualizedTracing to determine area of opening
Reveals degree of calcification
Thickness of valve leafletsInvolvement of subvalvular apparatus
Doppler
Estimates valve area based on blood flow
Therapy
All Mitral StenosisAnticoagulants to prevent embolism
Atrial fibrillation control
Digoxinβ-blockers or CCBs
Diuretics PRN
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Relief of dypsnea
Relief of right sided heart failure symptoms
AB prophylaxis for SBESurgical intervention
After onset of symptoms before pulmonary hypertension supervenes
Cardiac catheterizationCommon intervention
Stenotic Valve Split
Young patient
Noncalcified valveWithout regurgitation
Vavlular replacement is indication majority of time
Operative mortality rate is ~ 5-10%Higher if Right ventricular failure has developed
Tissue valves
Less risk of thromboembolism
Replaced 7-10yrs s/pPercutaneous balloon mitral valvuloplasty
Viable alternative to sx commissurotomy
Balloon inflated to mechanically disrupt fused leafletsMarked improvement in degree of stenosis
Increased functional capacity
Echocardiography is useful for selectionPatients who are good candidates
Thin valve leaflets
Preserved valve leaflet mobilityLess calcification Minimal involvement of the subvalvular
apparatus
May make co-existing mitral regurgitation worse
Mitral Regurgitation
Hemodynamic Consequences & Natural History
Multiple pathologies can cause
Rheumatic mitral valve disease
Papillary muscle dysfunction
Infarct at base of muscleDistortion of ventricular anatomy
Prevents adequate closure of valveEndocarditisDestroys the valve or supporting chordae
Massive calcification of the mitral annulus (rare & unknown reason)
Process of Mitral regurgitationLeft ventricle ejects blood back into left atrium during systole
Left ventricle adapts well to increased volume burden
End-diastolic pressure does not rise until late stages of illness
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Lower pressures result in less incidence of
Pulmonary edema
HemoptysisSystemic embolization
Left Ventricular failure eventually occurs
Low cardiac outputExhaustion
Exercise intolerance
Can predominate over other symptoms of pulmonary congestion
Acute Mitral RegurgitationHemodynamic compensation is not present
Catastrophic
Accompanied by shock & acute pulmonary edemaSurgical intervention may save pt
Caused by
Papillary muscle rupture
Myocardial infarctionChordae rupture in patients with chronic rheumatic mitral disease
With or without superimposed endocarditis
Physical Findings
MurmurHolosystolic Murmur
Heard at cardiac apex
Radiates typically posteriorly into axilla
Occasional radiation to baseConfused with aortic stenosis murmur
Accompanied bySoft or absent S1Loud S3 that may be followed by short diastolic rumble
Chamber enlargement
Often felt on palpation as a gentle rocking motion
Therapy
Evaluation
Serial assessments of left ventricular size & function
Rate control of atrial fibrillation
β-blockers
DigoxinCCB
Early symptoms treated withDiuretics
After load reduction
ACE inhibitorsCatheterization with contrast
Needed eventually
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Evaluate degree of mitral regurgitation
Determine extent of contribution
Disease of ValveDisease of myocardial muscle
Disease of papillary muscle
Considerations for surgery
1. Patient has symptoms2. Left ventricular ejection fraction worsens acutely3. Left ventricular end-systolic dimension approaches 45mm
Goal of timings
Perform surgery before irreversible left or right ventricular failure occurs
Mitral valve may be repaired in some or replaced in othersAcute mitral regurgitation is an emergency
Intra aortic balloon pump if necessary
Urgent surgical correction
Mitral Valve Prolapse
The “Click murmur syndrome”Mitral valve produces distinctive systolic murmur
One or more midsystolic clicks
Usually from redundant mitral leaflet tissueCommon syndrome
Up to 5% of adults
Commonly diagnosed in young women
Often asymptomaticOver diagnosed recently
Potential complicationsEndocarditisAcute fulminant mitral regurgitation
Transient cerebral ischemia from valvular emboli
Ventricular and atrial arrhythmiasSudden death
Antibiotics prophylaxis for SBE
Aort ic Stenosis
Hemodynamic Consequences & Natural History
Three major causes1. Age
a. Usually over 70 b. Systolic murmur frequently presentc. Calcification & stenosis may result
2. Rheumatic fevera. Rarely sole involvement of Aortic valve b. Usually combined with mitral and sometimes tricuspid valve
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3. Congenitally bicuspid valvea. Isolated aortic stenosis b. Usually younger than 60 years oldc. Functions normal at birth
i. Becomes scarred
d. Symptoms onset ~ 4
th
or 5
th
decadeDuring normal systole
Aortic valve is open
Ventricular & aortic pressures are equal
During stenotic systolePressure gradient develops across valve
Asymptomatic with early stages of lesion
Critical lesionPeak systolic gradient may exceed 50mmHg
Pressure in ventricle is 50mmHg>Aorta
Ventricle hypertrophy & myocardial O2 demand increases
End diastolic pressure risesLoss of left ventricular compliance
When any one of a triad of symptoms occurs
Life expectancy with out surgery is less than 5 years15-20% will die suddenly
1. Anginaa. Life expectancy ~ 5yrs b. Reflects inability of coronary flow to meet requirements for hypertrophied
tissues
c. No concurrent atherosclerosis in about ½ of the patientsd. Characteristic similar to CAD angina & responds to TNG
2. Syncopea. Life expectancy ~ 3 years b. Accompanies exertionc. Origin unknown
3. Heart failurea. Life expectancy ~2 years b. Most ominous symptoms associated with left ventricular failure
i. Dypsnea on Exertion (DOE)ii. Orthopnea
Physical findings
MurmurRough
Low pitched
Best heard at base of heartRadiates to neck along carotids
Begins after S1 and peaks midsystole
Crescendo-decrescendo patternImpulse of the large left ventricle is
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Displaced
Discrete
SustainedSignificant stenosis
Systolic thrill palpable at base
Corotid pulses feel weakImpulses delayed
Non-Compliant ventricle
S4 gallop
As disease progressesAortic closure
Progressively delayed
Producing single S2 soundA2-P2 splitting (paradoxical splitting)
Systolic pressures are not abnormally low
Qualities of murmurs do not correlate to severity of stenosis
Better guide to severity isQuality of the carotid upstroke
Presence of systolic thrill
Delay of A2
Diagnostic findings
Obstruction of left ventricular outflow produces concentric thickening of ventricular wall
Radiograph appears normal
Left atrium may be enlarged
Non-compliant ventricleAssociated mitral valve disease
ECG findings of left ventricular hypertrophyIncreased QRS voltageSecondary ST & T wave abnormalities
ST-segment depression
T-wave inversionIn lateral (I & avL)
Apical (V4-V6)
P waves may show evidence of left atrial enlargementLeft bundle branch block
Intraventricluar conduction defects
Echo Cardiogram
Thickened leaflets Narrowed aortic orifice
Left Ventricular hypertrophy
Doppler EchoPeak instantaneous gradient
May be different from catheterization values
Superimposition of peak instantaneous & catheterization values gives Peak toPeak Gradient (difference between aortic & ventricular pressure)
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Mean gradient is the difference between average ventricular & aortic pressure
during systole
Mean gradient more usefulBasis for management decisions
Once left ventricular dysfunction occurs
Gradient may drop paradoxicallyDecompensated ventricular pressure can’t sustain as much force
Valve area
Calculated from data derived from cardiac catheterization
EchocardiographySignificant stenosis – 0.7cm
2
Moderate stenosis 0.7-1.0 cm2
Mild stenosis 1 cm2 or more
Therapy
Complications of surgery & prosthetic valve are significant
Delay catheterization and sx until onset of symptomsBefore evidence of significant left ventricular failure
Exception to the ruleAsymptomatic young patient with significant stenosis
Sudden death may occur if sx is delayed
CatheterizationDetermine pressure gradient
Degree of accompanying CAD
Ensure obstruction is valvular and not subvalvular or supravalvular
Medical ManagementDiuretics for CHF
Salt restriction for CHFTNG for anginaValve replacement once significant stenosis is confirmed
Operative mortality rates
5% patients in good condition30% patients in heart failure
Good prognosis even in elderly
Percutaneous aortic balloon valvuloplasty for poor sx candidatesRe-stenosis within 6 months
Temporizing procedure only
Unlike mitral valve, aortic valve can’t be rx in patients who are sx candidates
Aort ic Regurgitat ion
Hemodynamic Consequences & Natural History
Isolated Aortic regurgitation caused by many of the same disease as aortic stenosis1/3 are rheumatic in origin
Syphilitic aortitis
Various disorders of the connective tissue
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Ankylosing spondylitis
Myxomatous degeneration
Distortion of the root of the aortic valveMarfan’s Syndrome
Hypertension
Major hemodynamic consequenceVolume overload of left ventricle
Compensates by dilation
Reflex peripheral vasodilation
Eventually left ventricular failure starts to occurAngina may develop
Medical emergency
Acute aortic regurgitationEndocarditis
Trauma
Rapid rise in ventricular end-diastolic pressure pulmonary edema and ventricle
may not maintain enough cardiac output
Physical Findings
Murmur
Decrescendo diastolic murmur
Occurring shortly after S2 Rheumatic Valvular disease
Best heard at left sternal border
Austin Flint murmur
May be mixed in with murmur of aortic regurgitationTiming & quality resemble mitral stenosis
Probably derives from regurgitatant stream striking anterior leaflets of mitralvalveLong standing aortic regurgitation
Reflexive vasodilation of peripheral arterioles
Widened pulse pressureDramatically reduced diastolic pressure
Distinctive pulse that rises & collapses rapidly
Pistol-shot sounds over large arteriesCapillary pulsations
Especially obvious in nailbeds
Called Quincke’s Pulses
de Musset’s signUvula, head or even whole body to bounce
Durozier’s sign
To-and-fro murmurMay be heard on compression of large arteries such as femoral
Cannot correlate signs to severity
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Diagnostic Findings
Chest X-Ray
Boot-shaped elongation of left ventricleECG
May suggest left ventricular hypertrophy
Echo CardiogramIndirect evidence of aortic regurgitation
High-frequency stuttering of anterior leaflets of the mitral valve causing
premature closure of mitral valveColor Doppler technique
Sensitive indication of aortic regurgitation
Therapy
Timing of surgery is critical
Considered when patients develop symptomsFollow asymptomatic patients closely
EchocardiographyFrequent clinical exams
Surgical indicationsBefore left ventricle end-systolic dimensions reach 55mm
Left ventricular ejection fraction falls below 55%
Acute Aortic RegurgitationAortic dissection
Bacterial endocarditis
Urgent surgeryMedical Therapy
Afterload reducing vasodilators
ACE inhibitorsCCB – Nifedipine & nitroprusside to temporize or non-surgical candidates
Rheumatic Fever
Generally disease of childhood & adolescence
Develops after a pharyngeal infection
Group A StreptococciReflects immunologic disorder triggered by infection
Immediate symptoms
FeverCarditis
Migratory polyarthritisLess common
Chorea – neuro disorder of sudden & uncontrollable jerky movements withemotional lability
Erythema marginatum
Evanescent serpiginous rash (WTF???) - a disappearing skin lesion with a wavyor indented border.
Subcutaneous nodules found over extensor surfaces of bony prominences
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Carditis affects the
Pericardium
MyocardiumEndocardium
ECG changes are common
May be a fulminant course leading to death fromValvular insufficiency
Heart failure
Arrhythmias
More often silentDamage presents later in life
Recurrent illness
Following acute attackMonthly intramuscular injections of benzathine penicillin
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Chapter 5 –
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Chapter 6 – Cardiac Arrhythmias
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Chapter 7 – Hypertension
Hypertension is associated with increased risk forAngina
MICHF
Renal FailureHemorrhagic & thrombotic strokes
Blood Pressures: Normal 120/80HTN 140/90
Mild HTN DBP 90-104
Moderate HTN DBP 15-114Severe DBP >115
JNC = Joint National Commission on Prevention, Detection, Evaluation &Treatment of increased blood pressure
6th
JNC doesn’t use term “mild” or “moderate”
Labile HTN (BP that fluctuates repeatedly and rapidly) Transient increase in BPwith stress or excitement
Not known if it caries the same risk as sustained HTN or if it will progress to
sustained HTN
Successful Treatment – regardless of HTN level all is possibleDecrease incidence & rate of recurrence of stroke
Diminishes Left ventricular hypertrophy
Decrease risk of CAD
Increase survival in patients with renal insufficiencyDecrease chance that patients with hypertension will develop Malignant
Hypertension
COMPLICATIONS
Elevated BP is not symptomatic by itself No demonstrated correlation to symptoms –i.e. headaches etc
Patients should understand treatment of HTN will not address specific complaints
Treatment is to prevent complications of long-term disease
Cardiac complications
Major risk factor in development ofCAD
Consequent Angina & MI
Sustained increase in mean arterial pressure leads to left ventricular hypertrophyConcentric hypertrophy of left ventricular walls from HTN
Increase in voltage in precordial leads of ECG
Change in the ST & T wave consistent wit left ventricular strain
Echocardiogram shows hypertrophy better than the EKG
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Evidence of left ventricular hypertrophyFrequently detected during physical exam
ECG of untreated patientsPalpation may reveal unusually pronounced & prolonged apical impulses
Eventually
Left ventricular dilation & CHF may develop
Aortic Dissection
Serious, but rare complication of long standing HTNThe forward, pulsatile blood blow
Produces intimal tears
Blood dissects between the intima & mediaVarious distances
Two sites of particular vulnerabilityWhere Aorta is non-mobile
1. Ascending aorta above aortic valvular ring
2. Immediately distal to the left subclavian arteryPredisposition fromHTNMarfan’s or other diseases that affect connective tissue
Clinical characterizationsAcute onset of severe tearing pain in anterior chest
Radiates to the interscapular region
Patients are often
Agitated (extremely)
AnxiousChest X-Ray
Widening of superior mediastinumConfirmation of DiagnosisContrast arteriography
Demonstrates false lumen
Or narrowing of true lumenTransesophageal echocardiogram
MRI
Spiral Computed Tomography
ConsequencesPotentially sever & fatal depending on location of tear
Three types of aortic dissection
Type I Aortic Dissection – The most lethalPatients younger than 65
Intimal tear in the ascending aorta
Dissection may extend distally to bifurcation½ of patients dissection leads proximally
Produces acute regurgitation or hemopericardium
Disasterous if false lumen occludes ostea of major branchesCoronary
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Carotid
Renal
Can lead to:MI
Arrhythmias
StrokeMessenteric Infarct
Acute Renal Failure
Cardiac Tamponade
Type II Aortic DissectionMajor factors
Disease of connective tissue – Marfan’s
Ascending AortaDoes not extend to origin of great vessels
Type III Aortic Dissection
Tears in descending aorta
Almost always elderlyWith atherosclerosis
HTN
Sequelae from HYPOperfusion to vascular tree distal to Left subclavianarteries
Therapy
Depends on site of tearType I & II
Surgical resection of involved portion
Medical therapy alone is dismalDeath results from
Compromise of critical vessels
Rupture of aorta into pericardiumType III – Amenable to medical treatment
Therapy directed to
Rapid reduction in BP
NitroprussideGanglionic Block drugs (Trimethophan)
Reduction of rate of rise in systolic pressure
β - BlockersSurgery for patients with
End organ compromise
Unrelenting pain
Radiographic evidence of progression
Renal complications
Aging leads to:Progressive thickening of intrarenal arteries
Hyalinization of glomeruli
May be accelerated by HTN
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Called nephrosclerosis
Small shrunken kidneys & azotemia (Azotemia Def: Retention of
excessive amounts of nitrogenous compounds in the blood. The toxiccondition is caused by failure of the kidneys to remove urea from the
blood & is characteristic of uremia.
HTN is one of the leading causes of renal failure
CNS compl ications
Devastating affect on intracerebral vasculatureTransient ischemic attacksThrombotic strokes
Rupture of intracranial aneurysmsHypertensive intracerebral hemorrhage
All the above can complicate course of moderate to severe HTN
More common end organ damage in CNS isRetinophathy of HTN
Fundiscopically detectable vascular changesArteriovenous nicking
HemorrhageExudates in a graded fashion
ETIOLOGY
Primary HTN
Origin of 95% HTN unknownMultifactorial
Involves complex interplay between
Hemodynamic affects of the CNSAutonomic Nervous System
Its circulating catecholaminesVolume of regulatory effects of Renin-Angiotensin-Aldosterone System
Hemodynamic measurements showsBP can be increased by decreases in peripheral vascular resistance
Secondary HTN
Problem with one of the control systems (mentioned above)Less than 5% of casesOften curable
Most likely young (65YO) Newly diagnosed HTN
Severe or accelerated HTN
HTN that is refractory with therapy
Only a few causes encountered with regularityRenovascular disease
Renal parenchymal diseaseDisease of adrenal cortex
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Pheochromocytoma
Coarctation of aorta
Renovacular disease
Goldblatt – 1934
Constriction of a single renal artery found to produce chronic hypertensionRenal hypoperfusion leads to an increase in renin release
Renin cleaves angiotensinogen into angiotensin I
Angiotensin I is cleaved again in the pulmonary circulation by ACE enzyme intoangiotensin II
Potent vasoconstrictor
Directly stimulates adrenal cortex to increase production of aldosterone (Na+
retention)
Renal Artery sclerosis is the most common cause of secondary hypertensionDoes it through the renin-angiotensin-aldosterone system
Most common cause
Other causes include Atherosclerotic narrowing (usually in elderly)Fibromusclular disease of renal arterial wall (young women)Localized aneurysms
Various space occupying lesions (i.e. cysts & tumors)
If secondary HTN is suspectedScreen for upper abdominal bruits
Best non-invasive test
Renal duplex ultrasound
Magnetic resonance angiographySensitivity to above tests is ~90-95%
More invasive testsMeasurement of plasma renin after captopril administrationRapid sequence IV pyelogram
Sensitivities to only 70-80%
Not as commonly usedRadionuclide renal perfusioin scanning with hippurate (Reflecting renal blood
flow) or diethyl enetriaminepentaacetic acid (DTPA) (Glomerulous filtration)
Extremely sensitive
Stop ACE inhibitors priorCaptopril induced changes are predictive to good response to
revascularization
Renal Digital Subtraction AngiographyDefinitive test to confirm or elimate diagnosis
Therapy
Angioplasty for discrete lesions that are accessible75% 1yr s/p are patent
4/5 have immediate improvement in BP
Medical TherapyUsually relies on ACE inhibitors
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Surgical bypass of affected vessels
Effective
Last resortOnly after Angioplasty & medical therapy are unsuccessful
Renal parenchymal Disease
Patients with end stage renal disease often develop volume dependenthypertensionLess commonly elevated plasma renin concentration is responsibleMedical management with meds & dialysis is usually effectiveNephrectomy rarely neededOccasionally
Acute glomerulonephritis develops HTN
Screening UA usually suggests
Aldosteronism
Primary AldosteronismExcess mineralocorticoid aldosteroneSuspect for in patients that present with
HTN & hypokalemia in absence of diuretic therapy
Most common cause is benign adenoma of the adrenal cortex
i.e. Conn’s SyndromeAlso caused by bilateral hyperplasia of the zona glomerulsa
Na+ & H2O retention with consequent volume expansion is responsible for the
elevated pressurePeripheral edema is rare
Diagnosis confirmed by
Elevated levels of aldosterone Normal levels of
Cortisol
Adrenocorticotropic hormone
Suppressed plasma renin concentrationResult of sustained volume expansion
TreatmentSurgical removal of adrenal adenomas immediately decrease blood pressureBilateral hyperplasia better managed medically
Surgery rarely reverses HTN
Patient becomes dependent on glucocorticoids
Spironolactone blocs aldosterone receptors & may normalize BPPatients with Cushing’s syndrome may also have HTN
Pheochromocytoma
Adrenal medulla effects BP via production & release of the catecholamines (epi &
norepi)Pheochromocytoma
Tumor of chromaffin cells of the adrenal medulla
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Uncontroled production of catecholamines HTN
HTN of pheochromocytoma
Classically paroxysmalBaseline of sustained HTN for most
Nervousness, palpation & orthostatic hypotension are common
Coarctation of Aorta
Congenital anomalyLocal constriction of aortic lumenProduces delayed & markedly diminished pulses in the lower extremities & HTNUncomplicated coarctation – with out any additional anomalies
Complains of headache or exertional claudication
Key findings on examDifference in systolic BP between arms & legs
In older children & adultsMusculature of lower extremities may be underdeveloped
Systolic murmur that originates from coarctationBest heard in back between scapulaeIf well developed collateral circulation pulsatile flow in the intercostal region
Chest X-RayAortic constriction adjacent to the silhouettes of Pre & post stenotic dilations (the
“3” sign) along the left heart borderWell developed collateral flow – erosion of inferior bony margins produce
pathognomonic rib notching
Echocardiogram or MRI can visualize coarctationTreatment
Surgical correction is curative in most
HTN may persist or reappear years laterSooner the surgery occurs, the less likely the patient will suffer from residualHTN
Livelong prophylaxis for infectious endocarditis is mandatory
GENETICS OF HYPERTENSION
Little known about pathogenesisSeveral single-gene deficits have been identified
Inherited in Mendelian fashion
Pathophysiologic pathway in the kidneys effectedAlters net renal salt reabsorption
Genetic studies attempting to identify associated genes in general populationunsuccessful
ASSESSMENT
Diagnosis requires confirmation of DBP >90mgHg & Systolic >149mmHgTwo occasions
4 weeks apart
Disagreement about what constitutes a complete physical exam
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Serum electrolytesParticularly Potassium level
Adequate screen
End organ assessment withRetinal exam
Plain chest filmECG
Urinalysis
Serum creatinine
Further workup for secondary hypertension ifHPI or PE suggests
Member of group at higher risk for secondary
CAD should be assessed with a lipid profile & fasting blood sugar
THERAPY
Weight reduction if obese
Decrease alcohol intakeModerate level (
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Peripheral β-blockade can elevate systemic vascular resistance
Claudication in susceptible persons
Side effectsVarious gastrointestinal complaintsCNS issues
Usually transientSodium retentionAmeliorated with diuretic
Bronchospasm
Results from the β-blockade of β2-receptors on bronchial smooth muscle
Blunting of sympathically mediated S/S of hypoglycemiaImpotence
Urinary retention
Abrupt withdrawal associated withRebound hypertension
Angina
Classes of β-blockers available Nonselective β-agonists
Pranolol
Nadolol
Timolol
Blocks β1 & β2 receptorsCan exacerbate or induce bronchoconstriction
Selective β-agonists
Atenolol
MetoprololSelect for
Cardiac β1 Minimizes risk of bronchospasm exacerbation
Labetalol
Unique β-agonist
Blocks some α-adrenergic receptors
Does not raise systemic vascular resistance like other β-blockersα- blockade causes vasodilationCombination of blocking effects offer an advantage in persons with renal
impairment or peripheral vascular disease
Angiotensin-Converting Enzyme Inh ib itors
Inhibits enzyme that converts angiotensin I to angiotensin IIDecreases peripheral vascular resistance
Blocks the release of aldosterone
Inhibiting sodium retention
Wide usage forHTN
CHF
Useful as single-drug therapy when combined with diuretic
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ContraindicationsPatients with underlying renal disease
Can hasten renal failureMonitor serum creatinine & blood urea nitrogen levels
Usually well tolerated
Captopril was first to be usedSide effectsDisturbances of taste
Proteinuria
Severe neutropenia (Rare)
ACE InhibitorsCaptopril
LisinoprilEnalapril
Many patients develop chronic cough
Agiotensin Receptor Blockers
Also effective in reducing BPLosartanCandesartan
Valsartan
Calcium Channel Blockers
NifedipineVerapamilDiltiazemReduce blood pressure by
Blocks the slow Calcium Channels
Decreasing contractile forceVasodilation
Diuretics
When used alone, can often reduce blood pressure to desired limitsUsed often in multidrug regimenMinimizes sodium retention that occurs with many other antihypertensive drugsThree classes of diuretics
Thiazides
Loop Diuretics
Potassium Sparing Diuretics
Each act at different site on nephronPromotes sodium diuresis
Diminishes extracellular fluid volume
PromotesTransient extracellular fluid decrease
With long-term use returns to normal volume levelsAntihypertensive effect is maintained
Possibly because of the effect of direct vasodilation
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Thiazides
Act on distal tubule
Prevents sodium reabsorption
Class includesChlorothiazide
HydrochlorothiazideClosely related
Chlorthalidone
Meolazone
Side effectsHypokalemia
Significant percentage of patients
MonitorSerum potassium at start of therapy
Checked at regular intervals
If serum level drops below 3.5mEg/L
Potassium supplementsSooner if patient is taking digitalis
Hyperglycemia
Hypertriglyceridemia (increase in serum cholesterol levels)Hypercalcemia
Hyperuricemia
May unmask latent gouty arthritisArrhythmias via potassium depletion
Side effects have encouraged treatment with β-blockers, ACE inhibitors & CCB
Loop Diuretics
Class includesFurosemideEthacrynic acid
Bumetanide
Acts on ascending limb of the loop of Henle
More potent natriuretic than thiazidesSide effects
Greater electrolyte disturbances
IndicationsPatients with impaired renal function
Patients who are relatively insensitive to effect of thiazides
Potassium-sparing diuretics
Act on distal tubule (same area as thiazides)
Three in classSprionolactone
Blocks action of aldosterone on distal tubule
May induce gynecomastia & menstrual irregularitiesTriamterene
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Independent of aldosterone
Amiloride
Independent of aldosteroneSide effects
Hyperkalemia
Epigastric distressWeak diuretics
Rarely used alone
Often incorporated with thiazides in combination tablets to minimize risk
of thiazide induced hypokalemia
Other agents
MethyldopaPrototype of centrally acting antihypertensive
Suppresses renin release
Produces only minimal orthostatic hypotension
Side EffectsSedation
DepressionImpotence
Reversible
Hepatic serum transaminasesHyperprolactinemia
Coombs-positive hemolytic anemia
Usage has declined with availability of better agents
ClonidineWorks through actions on CNS α-receptors
Characterized byReduction in cardiac output at restReflex control of vascular resistance is not impaired
Orthostatic hypotension is a rare complication
Side effectsDry mouth
Constipation
Guanabenz & Guanfacine are similar drugs and also act on CNS α-receptors
Doxazosin, prazosin & terazosinα-blocking agents
Blockade of postsynaptic α1-receptors
VasodilationDrop in blood pressure
Side effects
Orthostatic hypotension that can be severeEspecially with first dose
Syncope may result
Usually combined with diuretic and other first line agents
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HydralazineVasodilation via direct relaxation of arteriolar smooth muscle
Short actingRapidly inactivated by the liver when taken po
Rapid reduction of bp can produce
Profound reflex tachycardiaFluid retention
Always given in combination with diuretic & sympathetic blocker
Lupus like symptoms with high dosage
MinoxidilSimilar to hydralazine, but is more potents
Combined with furosemide & a sympatholytic agent
Effective at controlling blood pressure where other meds cannontDoes not compromise glomerular filtration
Used in patients with renal disease
Side Effects
HirsutismOnly used in patients with severe hypertension
HYPERTENSIVE CRISIS
When severe hypertension & end-organ damage evolve over hoursPotentially fatal syndromeRare in hypertensive patientsSyndrome is referred to as
Accelerated or Malignant hypertension
Blood pressure that precipitates crisis is variable with each patientDBP higher than 140mmHg used for convenience
Associated physical findings more important than actual DBPPhysical findings
Severely increased DBP
Advanced retinal changes
Papilledema (optic disc swelling caused by increased intracranial pressure)Progressive oliguric renal failure
Hypertensive encephalopathy
Clinical presentationHeadache
Seizures
Coma
AgitationPulmonary edema
MIAcute renal failure
Intracranial hemorrhage
PathogenesisUnclear
May be associated with
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Intimal hyperplasia of small renal arteries
Produces fibrinoid necrosis
Leads to high level of circulation reninUsually no evidence of precipitant
Accelerated hypertension may also be caused by
PheochromocytomaElevated CNS pressures
Eclampsia
Commonly, abrupt withdrawal from some HTN agents
PropranololClonidine
Guanabenzine
MOIs with foods containing tyramine release of catecholamines
Rapid & controlled treatment to prevent renal damageStroke & blindness may occur from rapid drop in BP
Initial goal of therapy
Decrease DBP to 100Treatment Nitroprusside, only when monitoring is available
Given IVMetabolized to cyanide & thicyanate
Metabolic acidosis
WeaknessCNS effects that can progress to coma
Labetalol (block both β & α – receptors
Decreases blood pressure byReducing peripheral vascular resistance
Cardiac contractility
Patients without neurologic, cardiovascular or renal compromiseSublingual nifedipine
Successful at reducing high pressures
Followed by several hours of observation
Patients who have had one episode of malignant hypertension are at increasedrisk for further episodes
Hypertension Meds
β-blockersPropranolol
NadololAtenolol
Labetalol
Timolol
VasodilatorsACE inhibitors
Angiotensin receptor blockers
Hydralazine
Prazosin
Doxazosi
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-Calcium Channel Blockers Nifedipine
NicvardipineAmlodipine
Verapamil
Diltiazem
DiureticsThiazidesLoop Diuretics
Potassium-sparring diuretics
Central-acting agentsMethyldopa
Clonidine
JNC VII Guidelines
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Chapter 10 – Pulmonary Function Tests
Used to detect, characterize & quantify pulmonary diseaseBasic testing includes
Airflow
Lung volumesDiffusing capacity
Additional testingABGsRespiratory muscle strength
Bronchial provocation studies
Cardiopulmonary exercise studies
SPIROMETRYDefinitive measurement of airflowIncomplete measurement of lung volumeProvides information about
Ventilatory or mechanical properties of the lungFlow rates assessed
Forced Expiratory Volume in 1 second (FEV1)
Volume of air exhaled out of the lung forcefully in the first second of a
maximal expiratory maneuverForced Vital Capacity (FVC)
Total Volume of air that can be maximally exhaled during a forced
maneuver
Values that are 80% or greater than predicted normal values are WNLFEV1/ FVC
Unitless unit
Describes change in expiratory airflow over the course of the maximalexpiratory maneuver
Values greater than 70% are normal
Abnormalities can be broken down into twoObstructive
Asthma
EmphysemaChronic bronchitis
Centrally located endobronchial tumors
Restrictive
Interstitial lung disease
Neuromuscular diseaseThoracic cage deformity
ObesityAlveolar consolidation
Common to all obstruction is a reduction in the airway lumen caliber duringexpiration
May be reduced by
Bronchial smooth muscle constriction (asthma)
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Excess mucus secretions
Mucus plugs (chronic bronchitis)
Increased airway collapsibility secondary to loss of elasticity(emphysema)
Obstructive lesion (Endobronchial tumor)
Obstructive physiologyCharacterized by a reduction of both FEV1 & FEV1/FVC Restrictive Lung Disorders
Reduce FVC
FEV1/FVC may be normal or increasedDisorders may result from
Neuromuscular diseases (amyotrophic lateral sclerosis)
Thoracic Cage abnormalities (Severe Kyphosis)Interstitial lung disease (Asbestosis)
Alveolar Disorders (Acute Respiratory distress syndrome)
Neuromuscular insufficiency will also result in reduced maximum inspiratory
force measurement (MIF)MIFEasy measurement
Not routinely performed with spirometryHighly variable results if patient does not give consistent maximal effort
Postbronchodilator SpirometryMeasurements before & after bronchodilator administrationIf there is improvement
Indicative of asthma
Increase in FEV1 A positive response is increase of 12% & 200mL 15 min s/p admin
Absence of + response is does not excludeDs may be in remission+Response with obstructive defect confirms
Reversible obstruction
Cardinal feature of asthma
False negativePatient takes bronchodilator before baseline
Patients should abstain from bronchodilator for 6 hours
DETERMINATION OF TOTAL LUNG CAPACITYDefinitive lung volume measurementTotal Lung Capacity (TLC)
Important when restrictive defect is suspectedAll lung volumes including FVC are reduced
Only restrictive defects should result in a reduction of TLC
In obstructive disease, TLC will actually be supranormal due to severehyperinflation & gas trapping
Measured byGas dilution techniques
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May underestimate TLC due to gas trapping in obstructive or
mixed disease patients
Results in lower than actual TLC Body Plethysmography
Measured using Boyles law
Special chamberGold Standard for measuring TLC & demonstrating restrictive
disease
Both techniques require special equipment
Not easy to perform
DIFFUSING CAPACITY OF CARBON MONOXIDEDLCO Also known as: Transfer FactorProvides measurement of the integrity of the alveolar-capillary interface in thelungs
Useful information on
How readily gases can cross the interface into pulmonary circulation
TestingPatient inhales a gas mixture containing COHold a breath with lung fully inflated for 10 secondsInspired & expired gas volumes & concentrations are measured
CO has affinity 200 X that of Oxygen
Abnormalities in alveolar-capillary membrane results in decreased transferDiseases affecting
Pulmonary vessels (Pulmonary vasculitits)
Interstitium (Pneumoconioses, hypersensitivity pneumonitis, idiopathic
pulmonary fibrosis & sarcoidosis)Alveloar space (Emphysema or ARDS)
False lowAnemiaFalse high
Polycythemia
Most labs report corrected value accounting for hemoglobin levelPulmonary hemorrhage will give supranormal levels because of excess hemoglobin
available for binding
Widespread opacities on chest X-ray & increased diffusing capacity suspect pulmonary hemorrhage
ARTERIAL BLOOD GASES & PH ABG & pH provide information about lung function: oxygenation & ventilation
HypoxemiaSubnormal oxygenation of blood
PaO2 decreases with age Normal PaO2 in upright position
104-(0.27 X Age)
4 pathophysiologic processes may causeHypoventilationVentilation-perfusion mismatch (shunting is extreme example)
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Low inspired fraction of oxygen (15% as opposed to normal 21%)
Low partial pressure of oxygen (High altitudes)
Diffusion abnormalities cause hypoxemia with exercise but less common at rest Hyp oventilation
Has elevated PaCO2
Alveolar ventilation fails to increase sufficiently with CO2 productionResults in hypercapnea
HypercapneaAcute or chronic
Common causesDepressed ventilatory drive
Sedative drugs
AnesthesiaMechanical abnormalities of lung
COPD
Muscle weakness
Treatment should emphasize restoration of normal ventilationVentilation-perfusion mismatch Most common cause of hypoxemia
Underventilated blood passes back to the heart poorly oxygenatedLow ventilation perfusion [V/Q] ratio
Oxyhemoglobin dissociation curve
Sigmoidal shapeBetter ventilated areas of lung cannot make up for poorly ventilated areas
Most obstructive & restrictive disorders due to alveolar filling cause
hypoxemia by this methodExtreme case of low V/Q
Right – left shunt
May be intrapulmonary (AV malformations)May be extrapulmonary (ventricular septal defect)
Refractory to supplemental oxygen
Suspect if + to oxygen in absence of radiographic changes
Diffusion Abnormalities
Destruction of capillary bed
Rapid red cell transit time
Alveolar & erythrocyte partial pressures cannot equalizeWorsens with exercise
Usually successful with supplemental oxygen
Hypercapnia
PaCO2 greater than 44mmHgMay result from compensatory mechanism for metabolic alkalosis – pH is
alkaline
May be caused by diminished central respiratory driveCompromised respiratory mechanisms
Muscle weakness
BRONCHIAL PROVOCATION STUDY
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Used to detect presence of airway hyperreactivityMost commonly used on suspected asthma patients with normal spirometry
Most common agent used is methacholine (cholergenic drug bronchoconstricition)
Delivers drug over timed intervals
Spirometry performed within 5 minutes of each doesSerial testing continues until FEV1 is decreased by 20%
A low PC20 is suggestive of asthma
A high PC20 rules out asthma
Bronchodilators administered at end to reverse
CARDIOPULMONARY EXERCISE STUDY Assessment of cardiovascular-pulmonary response to exercise
Only test that assesses exercised lung
Complicated procedureIndications
Unexplained dypsnea
Assess work capacityAssess factors limiting exercise tolerance
Evaluate disease progression & treatments over time
MeasuresCV & ventilatory parameters
Oxygen consumption most important measurement
Determinants of the pulmonary response to exercise includeCentral respiratory drive
Neuromuscular function
Thoracic cage anatomyConducting airways
Gas exchanging units (alveolar ducts & sacs)InterstitiumPulmonary vasculature
Determinants of Cardiovascular responseHeart rateStroke volume response
Integrity of peripheral vasculature
Ability of muscle beds to utilize delivered oxygen
Normal Cardiac response to exerciseProgressive increase in
Minute ventilation
Heart rateStroke volume
Oxygen consumption
Should be able to exercise beyond anaerobic threshold
Abnormal cardiovascular responseHR response excessive for workload
Early lactic acidosis
Abnormal pulmonary response
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>50 breaths per minute (virtually dx of restrictive lung ds)
Desaturation (interstial lung disease & emphysema)
Inability to reach anaerobic threshold (emphysema)development of post exercise obstructive ventilatory defects (exercise induced
asthma)
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Chapter 11 – Asthma
7% of US population
NAEPP – National Asthma Education & prevention Program
Characterized by
Airway obstructionAirway inflammation
Increased response to airway stimuliPrevalence is on the rise
PATHOGENESIS & PATHOLOGY
Contributions
GeneticsHeredity
Associated with chromosome 5q31-q33 bronchial hyperreactivity and
elevation of IgEEnvironment
Tobacco smokePossibly infectious components
Asthma is an inflammatory response
Influx of inflammatory cells tendency for bronchospasm
Bronchial hyperreactivity present in all cases of asthma
Relevant inflammatory cellsBronchial mucosal mast cells
TH2 Helper lymphocytes
EosinophilsInteraction via
Proinflammatory cytokines
LeukotrienesAdhesion molecules
Growth factors
Physiological findingsAcute & chronically inflamed airways
Thickened airway mucosa
Desquamated epithelial cells
Hypertrophy of smooth muscleThickened basement membrane
Increased number of inflammatory cells
CHRONIC ASTHMA
Clinical & laboratory presentationTriad of chronic Asthma symptoms
Episodic dypsneaCough
Wheezing in response to diverse stimuli
Mild end of spectrum
Exercise induced asthmaRespiratory symptoms 15-20 minutes s/p exercise
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Putative triggers
Respitory tract heat
Water lossExercise in cold, dry air
Cough variant asthma
Seldom or never notices wheezing or SOBMethacholine challenge to prove bronchial hyperresponsiveness is
responsible for cough
Occupational asthma
Difficult to dxConfirmed with portable peak flow meter
Rare patient with years of untreated airway inflammation
Structural remodeling of the airway“fixed” obstruction
Mimics COPD
Nocturnal Asthma
Brittle diseasePropensity for fatal result
Marked diurnal swings in airway caliber (peak flow variability >30%)
Early morning cough, dypsnea & wheezingResponsive to bronchodilators
“Morning dipper”
Unstable asthmaticDemands aggressive therapy
Rarely is distinction made between extrinsic & intrinsic asthmatics today
Search for precipitants is still vitalAsthma precipitants
Pollen
The house dust miteAnimal dander
Iodine
Change in air quality
Yellow dye NSAIDS
Aspirin sensitivity associated with the syndrome of nasal polyposis &
sinusitisExtrapulmonary disease – may mimic or complicate asthma
CHF
Pulmonary embolismUpper airway obstruction
COPD
Bronchiectasis
Cystic fibrosis Nasal disease
GERD
Family hx is helpful in dx
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Physical Examination
Supports diagnosis
Assess the possibility of other disordersSkin – may show eczema
ENT exam
All make treatment more difficultRule out nasal polyps
Sinus Ds
Cobblestoned posterior nasopharynx – suggestive of postnasal drip
Diffuse polyphonic expiratory wheezes with prolonged expiratory phase is typicalof asthma
Cardiac exam
Possible left ventricular failure or pulmonary hypertensionFinger clubbing – not indicative of asthma, but may show coexistent interstitial
lung disease
Laboratory work
CBC with Wright’s Stain for determining total eosinophils>450/mm3 should prompt test for plasma IgE levels & consideration of
bronchopumonary aspergillosis
Treatment of increased IgE with corticosteroids preemptively improves outcomePulmonary function tests
Should confirm reversible airway obstruction
Asthmatics with chronic oral corticosteroids & a propensity for nocturnal asthmashould record peak flows twice a day
Persistent small airway inflammation causes a decrease in flow rates at low lung
volumes, hyperinflation & hypoxemiaManagement
Goals of treatment include
1. Prevent chronic & troublesome symptoms2. Maintain (near) normal activity levels3. Prevent recurrent exacerbations of asthma & minimize the need for ED visits or
hospitalizations
4. Provide optimal pharmacotherapy with minimal or no adverse effects5. Meet patients’ & families’ expectations of and satisfaction with asthma care
Attainment extends beyond pharm & includes
1. Education2. Need for objective measures of airways obstruction3. Moderation compliance, proper use of inhaler devices4. Environmental controls5. Self management plans to be followed at home if need arises
Asthma severity
Classified based on symptoms into 4 categories
1. Mild intermittent2. Mild persistent3. Moderate persistent4. Severe persistent
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Therapeutic recommendations
Based on a stepwise approach
Attempt to taper down to lower classificationPharmacotherapy of asthma is divided into two broad classifications
Quick-relief medications – treats symptoms & exacerbations
Selective short-acting β2 agonistsLong-term controller medications – to achieve & maintain control
Corticosteroids
Long-acting β2 agonists
Cromolyn Nedocromil
Antileukotriene agents
Infrequent symptomsβ2 agonists on an as needed basis
MDI – Metered Dose Inhaler
Acceptable β2 specific agents
AlbuterolSalmeterol
Pirbuterol
ToxicityThrush
Dysphonia
Obviated by proper inhaler techniqueCromolyn & nedocromil alternative anti-inflammatory agents virtually free of
toxicity
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Chapter 14 – Deep Venous Thrombosis and PulmonaryThromboembolism
PREVALENCE AND PATHOGENESIS100K deaths per year30-50% recurrence in untreated patientsOccurs in setting of
Vichow’s Triad
1. Endothelial Damage (Trauma to venous intima)2. Venous stasis3. Hypercoagulable state
Single most important risk factor is previous DVT or PTE
Hypercoagulable StatesCancer
Oral BCP
AgeCertain myeloproliferative conditions
Familial hypercoagulable states
Deficiency in proteins C & SDeficiency in antithrombin III
Antiphospholipid antibody syndrome
Prolonged aPTT (activated partial thromboplastin time)
10% of patients with heparin induced thrombocytopeniaPresence of intravascular devices
PATHOPHYSIOLOGYOnce established tend to drift proximallyIf free floating can cause problem in pulmonary circulationIf large clot moves through right ventricle systemic hypotension may resultMost originate from deep venous system of thighsOrigination below popliteal fossa
Low risk for propagation & embolism
Still require anticoagulation
Other sourcesPelvic & renal veins
Right atrium & ventricleCentral Venous Catheters
Clinical & Laboratory ManifestationsResult from obstruction of pulmonary vasculature by clotPulmonary vasoconstriction
Mediated by platelet-derived substances
Serotonin
Possibly by imbalance betweenVasoconstrictor endothilin
Endothelium-derived nitric oxide
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Resultant increase varies depending on the presence or absence of
preexisting pulmonary vascular disease
Normal individuals may show no changes until 40% occlusionCOPD may have greater disproportionate changes after small embolism
Risks for hemodynamic compromise from PTE are greatest in
Patients with existent compromise right ventricular function i.e. cor pulmonale secondary to primary pulmonary hypertension or global
cardiomyopathy
Pulmonary Vascular ObstructionCompromises cardiac output and causes gas exchange abnormalitiesThe obstruction
Creates areas with high V/Q ratios (wasting ventilation)
Increases ventilatory requirementsLarge saddle emboli may cause frank hypercapnia
More common
Hypoxemia
Vascular obstruction has diverted blood to normal (low V/Q)regions of the lung
As a result of vascular injury from mediator release (vasc perm)
Ischemic atelectasis leading to right-to-left shunt fractionOccasionally
Profound and refractory hypoxemia develops
Increase in right atrial pressure drives blood through potentially patent foramen ovale
Normally
Emboli resolve over days to weeks via endogenous thrombolysis1% large proximal clots fail to resolve and recanalize
Develop slowly progressive pulmonary hypertension cor
pulmonale
CLINICAL AND LABORATORY PRESENTATIONHPI
Leg painSwelling
PEIpsilateral
Edema
Erythema
Tenderness
Palpable venous cord½ DVT cases are clinically silentNegative D-dimer test usually rules out large clot, but can be negative for smalleronesContrast Venography
Gold standard for dx
Other sensitive tests do exist that are less invasive
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Equally useful & less invasive testsSerial Impedance plethysmography (IPG)
Ultrasound (US) both color flow & duplexSensitive enough for non-calf thrombosis in the lower extremities
Initial Rx Dx Test
If negative in high risk patient – repeat every 3 – 10 daysCT & MRI are being integratedSigns & SymptomsDepend on
Antecedent cardiopulmonary reserveClot load
Presence of pulmonary infarction
Recurrence of PTEDegree of endogenous thrombolysis that follows embolic event
Rare variantsChronic recurrent small emboli & chronic large vessel pulmonary emboli
Present withInsidious onset of dyspnea on exertion
Mimic primary pulmonary hypertension
10% of acute cases imply pulmonary infarction has occurred. Common in CHFwhere bronchial artery & collateral blood flow is compromisedFever
OccasionalRarely higher than 39 C (102.2 F)
Peaks on hospital day 1
TachypneaRate less than 16 can rule out PTE
Hypotension – suggestive of massive PTE Also
Right-sided ventricular heave
Third heart sound
Tricuspid regurgitation murmur
Increased P2 JVD (Jugular Venous Distention)
If pulmonary infarct has occurred
Pleural friction rubDullness to percussion at site of associated pleural effusion
Consolidation above
Occasional overlying tenderness
Lab tests None are sufficiently sensitive or specific to confirm dx
D-dimer by ELISA (Enzyme linked Immosorbent Assay)
May have negative predictive value, but can’t rule out definitivelyPaO2 is normal in 10% of patients
Alveolar-arterial O2 gradient is usually widened
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EKG Abnormalities
Sinus tachycardia is most common
New atrial fibrillation may be presentP pulmonale and right ventricular strain with massive PTE
Right bundle branch block
Right ventricular hypertrophyClassic S1Q3T3 pattern
Chest X-ray is usually normal
2-3 days post infarct, may show atelectasis
Westermark’s SignLoss of vascular markings in the same area as the involved vessel
Hampton’s Hump
Radiopaque density abuts the posterior diaphragm and protrudestowards the heart
Lung Perfusion Scan
Screening test of choice
Injection of radioactive albumin macroaggregates into venous circulationSlightly larger than pulmonary capillaries
Areas of under perfusion are absent of radioactivity
Normal essentially rules out PTEAbnormal means only there is a process compromising perfusion & not
necessarily a PTE
Inhalation of radioactive gasIncreased specificity
Continued ventilation to a segment absent perfusion is highly suggestive
of PTEPositive test treatment without further testing
High probability V/Q lung scans are one of the following
1. Two or more large segmental perfusion defectsa. Without corresponding ventilation or roentgenographic
abnormalities
2. Two or more moderate segmental perfusion defectsa. Without matching ventilation or xray abnormalities b. Plus one large mismatched segmental defect
3. Four or more moderate segmental perfusion defects without ventilation orx-ray abnormalities
Significant numbers of patients with low & intermediate V/Q have PTE
documented by pulmonary angiography
Patients with high suspicion for PTE should have further testing to r/o PTESerial non-invasive tests to rule out DVT in extremities
Pulmonary angiographyDefinitive test for PTE
Most specific radiographic signs of acute PTEIntraluminal filling defect
Vessel cutoff
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Chronic large vessel PTE difficult to detect
Recanalization of vessel mimics normal blood vessels
Spiral high-resolution CT & Magnetic resonance angiographyShows promise for dx of acute PTE
Valuable in ID of large-sized central or lobar PTE
Sensitivity for smaller clots is lowerDon’t use to exclude dx
Chronic large vessel PTEPulmonary angioscopy procedure of choice
PREVENTION AND THERAPYProphylaxis
Several regimens can be used Nature & number of risk factors should influence
Young patient with uncomplicated illness & postop patient at risk for wound
hematomaElastic stokings
Pneumatic compression of lower extremitiesDecrease stasisActivates endogenous thrombolytic pathways
Pharmacology
Low-dose (5000 units bid) of subcutaneous heparin
Heparin-induced thrombocytopenia is a contraindication.Ineffective after surgery where large amounts of tissue
thromboplastin are released (hip & knee sx)
Patients with multiple risk factors should receive both mechanical and medicaltherapyPatients with hip & knee replacements have VTE incidence between 50-70%
Aggressive therapyLow Molecular weight heparin (LMWH) subcutaneous or oral warfarinstarted pre-op
Anticoagulat ionInhibition of the cascade prevents propagation of the clotEndogenous thrombolytic mechanisms work to dissolve it
All patients with suspected or documented DVT or PTE should receive heparinHeparin
Combines with antithrombin III & prolongs the aPTT
Therapeutic range is 1.5-2.5 X control
Failure to move into the therapeutic range within 24 hrs of presentation increases
incidence of recurrenceIV bolus between
5000 – 1000 IUIV drip to maintain levels
Checked initially q4h and adjustments made
LMWHAlso approved therapy
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Advantages are
Higher bioavailability
Less protein bindingDecreased clearance
Prolonged half-life
More reproducible anti-coagulant activity No need for serial monitoring
Warfarin therapy5-10mg qd
With not before heparinInhibits coagulation by depletion of vitamin k-dependent pathway
Factor II, VII, IX & X
Endogenous anticoagulants protein C & STransient hypercoagulable state may result transiently without starting heparin
first
PT time – reflects extrinsic pathway
Dependence on factor VII (reflects index of warfarin anticoagulation)INR
Goal is 2.0-3.0
Takes 3-4 days after initiation of therapy to be in therapeutic rangeHeparin & warfarin therapy should overlap for 5 days
Complication of anticoagulation therapy is bleedingPoorly predicted by aPTTWell correlated with warfarin
At risk if:
INR over 4.0Increased Age
CNS ds
Peptic ulcer dsTrauma
Prior surgery
LMWH & bleeding is controversial
If anticoagulation is contraindicated – IVC filterHeparin can induced Immunoglobulin Thrombocytopenia (HIT)
1-3%
5-15 days s/p initiation of therapyMore common in those receiving heparin in previous 3 months
More common with unfractionated than LMWH
5% of HIT patients have disseminated intravascular coagulationPlatelet count monitored qd in patients receiving heparin
Discontinue if HIT develops
Two agents used to treat
Danaparoid sodiumAncrod (snake venom in trials in Europe)
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Additional complications of warfarinBleeding
Skin necrosis (vit C deficiency and malignancy)Teratogenesis
Systemic anticoagulation should continue for 3-6 months after DVT or PTE
Life long in presence ofPersistent hypercoagulability
Chronic autoagglutination
Thrombolysis Agents dissolve thrombi by
Activating plasminogen to plasmin
Degrades fibrin
To soluble peptides
Thrombolytic AgentsStreptokinase (SK)
Urokinase (UK)
Tissue Plasminogen Activator (tPA)Activates plasminogen associated with clot
All above are equally effective in treatment of DVT & PTEAnistreplase (APSAC)
Less systemic effect than SK
Less depletion of circulating plasminogen
Expensive & no proven benefit over SK
Thrombolytic therapyDecreases the frequency of the postphlebotic syndrome assoc with DVT
Most physicians use thrombolysis in PTE ifClot burden is high
Hemodynamic instability refractory to volume resuscitationSK is cheaper than UK use if no streptococcal antibodiesSK
IV bolus followed by 24 hour infusion for PTE (48-72 hrs for DVT)
tPA
2hour 100mg infusionWhen aPTT or thrombin time has returned to less than 1.5 X the control heparin is
started without a bolus
Major complication of thrombolysisBleeding
Primarily at venipuncture sites
Trauma sitesRecent Sx or internal bleeding is absolute contraindication
Surgical EmbolectomyPatients with massive pulmonary embolismPersistent shock
Hypoxemia
Requires cardiac bypass
Mortality rate 50%
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Chapter 16 – Acute Respiratory FailureDivide ARF (Acute Respiratory Failure)
Hypoxemic/Nonhypercapnic
Hypercapnic/Hypoxemic
The two above have different etiologies, findings & therapeutic ramifications
HYPOXEMIC RESPIRATORY FAILUREOccurs with combo of
Low V/QElevated Right-To-Left shunt
DepressesPaO2
Alveolar space withPus
Edema
FluidBlood
Hypercapnia generally not associated
Usually overcome with supplemental oxygenHYPOXEMIC RESPIRATORY FAILUREPathogenesis
Associated DsCHF
Cardiogenic pulmonary edema
PneumoniaAcute lung injury (ALI)
Acute (or Adult) Respiratory Distress Syndrome (ARDS)
ALI & ARDSFluid infiltrate from capillary leak of noncardiogenic protein-rich edema
Differentiated by PaO2/FiO2 ratio (Arterial Oxygen level/InspiredOxygen) 300-200 mmHg respectively
Clinical Scenario – one or more of the following risk factorsAspiration
Pneumonia
SepsisMultiple blood transfusions
Drug o