Fishman's Outline

8/17/2019 Fishman's Outline

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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


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


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

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