Diseases of the Pulmonary Circulation

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Diseases of the Pulmonary Circulation

• J.B. Handler, M.D.
• University of New England
• Physician Assistant Program

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Abbreviations

• PE- pulmonary embolus
• DVT- deep vein thrombophlebitis
• CO- cardiac output
• HF- heart failure
• OCP- oral contraceptive pill
• PAP- pulmonary artery pressure
• V/Q- ventilation/perfusion
• CVP- central venous pressure
• RR- respiratory rate
• P2- pulmonic valve component of the 2nd heart
  sound (S2)
• Vit-vitamin
• Dx- diagnosis
• INR- international normalized ratio

• S4- abnormal 4th heart sound
• NSST-T- non specific ST-T wave changes
• ST- sinus tachycardia
• ABG- arterial blood gas
• PuVR- pulmonary vascular resistance
• PPH- primary pulmonary hypertension
• RAE- right atrial enlargement
• RVE- right ventricular enlargement
• S2- second heart sound
• Rx- treatment
• PTT- partial thromboplastin time

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Pulmonary Thromboembolism

• Embolization of thrombus from the venous system
  into the pulmonary arterial circulation common,
  serious and life threatening
• 200,000 annual mortality in USA
• 3rd leading cause of in-hospital deaths
• Majority of deaths from PE unrecognized until
  post-mortem
• 5-7 mortality rate of diagnosed cases with a
  40-50 mortality rate of undiagnosed cases

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Pulmonary Embolism

• The presence of DVT should always sound an alarm.
  Prior DVT or PE carry a substantial risk for
  subsequent PE.
• Symptoms Often very difficult to recognize as
  symptoms are not specific to PE.
• 97 of patients with PE will have at least one of
  the following tachypnea, dyspnea, pleuritic
  chest pain (infers infarction). About 1/3 of
  patients will have tachycardia.

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DVT
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Pulmonary Thromboembolism

• DVT is the most common site of development of
  thrombus. Usually popliteal and/or iliofemoral
  vein involvement with subsequent embolization
  (50-60) to the pulmonary circulation.
• Calf involvement alone carries much less risk of
  significant embolism.
• Calf vein propagation to popliteal and
  iliofemoral veins occurs in 20 of patients with
  initial calf involvement.
• Pelvic vein thrombosis also common source.
• 50 cases of PE lack characteristic symptoms
  essential to have high index of suspicion.

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Risk Factors for DVT

• Venous stasis Immobility, post-op (large
  operations, orthopedic procedures), post stroke.
• Increased CVP Decreased CO, CHF, pregnancy.
• Hypercoagulability Meds (OCP), diseases
  (malignancy), and inherited- several forms
• Factor V Leiden A hereditary hypercoagulability
  disorder common (3 heterozygous incidence) in
  healthy adults. 20-30 of patients with DVT have
  this disorder.
• Factor V Leiden Modified clotting factor V,
  resists degradation by activated Protein
  C??coagulation.

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Intracardiac Pressures
4-12
4-12
4-12
4-12
4-12
4-12
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Pathophysiology

• Obstruction to pulmonary vascular bed by
  thrombus.
• Vasoconstriction develops in the pulmonary
  arteriolar bed (?PuVR) as a result of
• Neurohumoral reflexes, hypoxia, and tissue injury
• Result is ?PAP.
• ? PAP?Rt heart strain ? ?CO? (RVH if PAP ?s over
  time) ? RV failure Cor Pulmonale.
• Impaired gas exchange ?alveolar dead space from
  vascular obstruction.

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Pathophysiology

• ?physiologic dead space, ?CO, hypoxemia and
  surfactant depletion result in atelectasis.
• Atelectasis contributes to shunting (below).
• Right to left shunting plays a small role
• Atelectasis.
• Large PE Redirection of blood flow into normal
  lung but if inadequate alveolar reserve?shunting.
• Loss of surfactant, edema and hemorrhage lead to
  decreased pulmonary compliance, work of
  breathing.

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Ventilation/Perfusion
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Symptoms

• Dependent on number/size of the emboli and
  pre-existing pulmonary status.
• Constellation of findings dyspnea, pleuritic
  (inspiratory) chest pain and tachypnea are
  predominant symptoms/signs others include
  palpitations, wheezing and hemoptysis.
• Note must have high index of suspicion in order
  to make Dx in many patients.

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Signs

• Signs Increased RR, tachycardia, crackles, S4
  gallop, decreased S2 splitting with increased P2
  friction rubs and cyanosis less common.
• Clinical findings of DVT present in only 30-40
  of patients with PE but 60-70 will have evidence
  of DVT by non-invasive imaging (see below).

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Investigational Findings

• ECG changes common ST, NSST-T changes.
• ABG Respiratory alkalosis, decreased PO2.
• Plasma D-dimer (gt300-500ng/ml) a degradation
  product of cross-linked fibrin- usually elevated
  in presence of thrombus (97 sensitivity), but
  not specific (45). Commonly combined with other
  diagnostic studies (CT angiography)?predicts
  likelihood of PE.
• CxR often abnormal- atelectasis, pleural
  effusions, pleural based infiltrates necessary
  to exclude other pulmonary pathology.

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Images.google.com
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V/Q Lung Scan

• Radioisotopes used to image ventilation and
  perfusion. Defects develop in areas of lung that
  remain ventilated without perfusion inaccurate
  in presence of other pulmonary pathology.
• Graded low (normal), intermediate and high
  probability for PE.
• Supplanted as diagnostic test by Helical CT
  angiography (below).

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Pulmonary Circulation Imaging

• Helical (spiral) CT Angiography Sensitive for
  proximal vessel thromboembolism overall 83
  sensitive, gt90 specific alternative to V/Q
  scanning as a screening procedure. More often
  done compared to V/Q.
• Pulmonary angiography reference standard for
  the Dx of PE- Invasive with 5 complication rate
  (contrast reaction, renal failure, arrhythmias)
  high sensitivity, specifity. Indicated when V/Q
  or CT scans are indeterminate, DVT studies are
  negative, and PE still suspected clinically.

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Helical CT Pulmonary Embolus
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Pulmonary Angiography
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DVT Studies

• If Dx is uncertain and DVT is proven, likely that
  PE is present if clinically suspected.
• Venous ultrasound with doppler Non- invasive
  test of choice for DVT.
• Contrast Venography reference standard-highly
  accurate and invasive, has been replaced by
  ultrasound which is non-invasive and easier to
  perform.

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Integrated Approach for Dx of PE Clinical
Features Diagnostic Testing
Clinical Probability of PE Score
PE likely gt4
PE unlikely ?4
Wells et. al
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Clinical Probability of PE
PE Unlikely
PE Likely
D-dimer assay
Helical CT-PA
Negative
Positive
Normal
Findings of PE
Rx for PE
PE Excluded
PE excluded
Indeterminate
- study
Current fig 9-1
LE US or Pulm angiogram
study
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Treatment of 1st PE

• Full anticoagulation for minimum 6 months or
  longer depending on risk factors for recurrence.
• Unfractionated heparin Binds to and potentiates
  antithrombin III? inactivates clotting factors
  IXa, Xa, XIa, XIIa retards additional thrombus
  formation.
• Administered by continuous IV infusion and
  requires frequent monitoring (highly protein
  bound) of PTT for dose adjustment for 5-7 days.
• Wt. Based dosing 80U/kg loading dose, then
  18U/kg/hr?goal PTT 1.5-2.5x control (46-70 sec)
• Risks Bleeding, thrombocytopenia.

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• Low Molecular Weight Heparin depolymerized
  heparin, less protein and cellular bound,
  increased bioavailability also given for 7 days.
  More predictive dose response, as/more effective
  than unfractionated heparin. Decreased risk of
  hemorrhage and thrombocytopenia 1-2x daily
  dosing (weight based) without need for lab
  testing.
• Warfarin- oral anticoagulant, blocks action of
  Vit K, inhibiting hepatic synthesis of Vit K
  dependent clotting factors (II, VII, IX, X).
  Initiated over 5-7 days (with patient on heparin)
  and continued for desired period of time. Goal
  INR (adjusted PT) of 2-3.

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Thrombolytic Therapy

• Streptokinase, Urokinase and t-PA directly lyse
  intravascular thrombi and accelerate resolution
  of emboli within 1st 24 hours compared to
  standard heparin therapy, but do not decrease
  mortality.
• Indications patients with massive PE at high
  risk of death (unstable on heparin).
• Contraindications active internal bleeding,
  stroke in prior two months, surgery or trauma in
  prior 6 weeks and uncontrolled hypertension.

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Surgical Interventions

• Mechanical or surgical thrombus extraction- last
  resort in a dying patient.
• Vena caval interruption Indicated in patients
  with DVT/PE that cannot be anticoagulated or
  recurrent PE while already fully anticoagulated.
  Vena caval filter/umbrella can be introduced
  percutaneously via internal jugular vein.
• Prognosis of PE if diagnosed lt 3 incidence of
  death from recurrent PE if initial event is
  recognized and adequately treated.

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Prevention of PE

• Identify patients at high risk for DVT lengthy
  hospitalization/immobilization, orthopedic
  surgery, esp. hip repair (incidence of DVT 10-20
  if untreated with prophylactic anticoagulation
  and other measures).
• Strategies for prevention-early
  ambulation-elastic stockings-mechanical
  compression devices-anticoagulation.

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Pharmacologic Prophylaxis

• Patients with high risk for DVT and PE
• Low doses (below full anticoagulation dose) of
  anticoagulants (?s risk of bleeding) decreases
  incidence of DVT/PE Unfractionated Heparin Low
  molecular weight (LMW) heparin
• Sometimes continued as OP (warfarin/coumadin) in
  patient likely to remain immobile.

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Pulmonary Hypertension

• Pulmonary circulation is a low pressure system
  with high blood flow and low PuVR (200 resistance
  units compared with 800-1000 RU for the systemic
  circulation.
• In a variety of disease states (e.g. PE) there is
  constriction of smooth muscle in the walls of
  pulmonary arteriolar resistance vessels.
• Pulmonary Hypertension is present when the PAP
  rises to a high level, inappropriate for a given
  level of cardiac output.
• PPH- rare idiopathic disorder in woman.

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Idiopathic (Primary) Pulmonary Hypertension

• No other underlying cardiopulmonary disease An
  arteriopathy. Medial hypertrophy, fibrosis and
  recanalized thrombi are common pathology
  findings poor prognosis- mean survival post Dx
  is 2-5 years.
• Marked ?PuVR and PAP.
• Association anorexigens, collagen-vascular
  disease.
• Fenflouramine appetite suppressants Marked
  recent ?in PPH (U.S. and Europe) similar events
  in 1960s with Amrinox. Both taken off market.

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Secondary Pulmonary HTN

• Reduction of x-sectional area of the pulmonary
  vascular bed
• Vasoconstriction Hypoxia from any cause (most
  important and potent stimulus), lactic acidosis.
• Loss of vessels Vasculitis, emphysema,
  interstitial dis.
• Obstruction of vessels Multiple or recurrent PE.
• Chronically increased pulmonary venous pressure
  (HF, mitral stenosis).
• ?pulmonary blood flow Congenital Ht Disease.
• Once present, secondary structural changes occur
  resulting in further destruction of vessels.

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Signs and Symptoms

• Dyspnea- initially exertional, then rest.
• Retrosternal chest pain (mimics angina) fatigue
  and syncope result from decreased CO.
• Physical Exam Narrowly split or single S2, ?P2.
• CxR Dilated main PA with pruning of vessels.
• Echo-Doppler best non-invasive tool RAE, RVE
  elevated PA and RV systolic pressure.
• Right heart cath precise measurement of right
  heart pressures essential to Dx and Rx.

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Treatment

• Treat underlying disease process if present.
• Supplemental chronic O2 if hypoxemic.
• Full anticoagulation PPH only
• Prostacyline (Epoprostenol, Treprostinil) via
  continuous IV infusion potent pulmonary
  vasodilator ?symptoms and mortality.

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Treatment

• Bosentan (Tracleer) new oral endothelin-1
  receptor antagonist for chronic PAH ?symptoms.
• Sildenafil inhibits phosphodiesterase type 5
  pulmonary vasodilator- improves symptoms.
• Lung or heart/lung transplant 50-65 2 year
  survival. Better long term survival with
  bilateral (vs. unilateral) lung transplant.