1. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Chapter 26 Pulmonary Vascular Disease

2. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Learning Objectives  State how many patients develop venous thromboembolism each year.  Describe how and where thromboemboli originate.  Describe how pulmonary emboli alter lung and cardiac function.  Identify the clinical features and diagnostic findings associated with pulmonary embolism (PE). 2

3. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Learning Objectives (cont.)  Describe how PE is diagnosed and managed.  Describe the hemodynamic findings associated with pulmonary hypertension.  Describe the possible mechanisms believed to be responsible for the onset of IPAH.  State who is at risk of the development of IPAH. 3

4. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Learning Objectives (cont.)  Identify the clinical features associated with IPAH.  Describe the treatment used to care for patients with IPAH.  Describe the pathogenesis and management of pulmonary hypertension associated with COPD. 4

5. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Introduction  Pulmonary Vascular Disease  Pulmonary vasculature is affected by pulmonary & nonpulmonary disorders  Degree of pulmonary hypertension is determined by severity of underlying disease  Nonpulmonary causes include Heart disease Connective tissue diseases Venous thromboembolic disease 5

6. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.6 Introduction (cont.)  Venous Thromboembolic Disease  Includes deep vein thrombosis (DVT) & pulmonary emboli (PE)  Major national health problem Up to 300,000 new cases annually (U.S.) 1/3 die in first hour of onset of symptoms (PE) >70% of patients who die of PE are not suspected before death

7. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Pathogenesis  PEs are most often detached portions of venous thrombi  Most often (86%), thrombi form in deep veins (DVT) of legs or pelvis  Conditions that favor thrombus formation (factors known as Virchow’s triad)  Venous stasis: i.e., immobilization in hospital  Hypercoagulable states  Vessel wall abnormalities 7

8. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.8 The three components that make up Virchow’s Triad are:

9. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.9 Pathology  Stasis in conjunction with trauma or presence of toxins results in thrombi  Thrombus fragment travels to lungs resulting in PE  PE is most frequent in lower lobes & right lung  Pulmonary hemorrhage or infarction are rare (<10%)  Bronchial circulation provides collateral circulation limiting risk of infarction

10. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.10 Pathophysiology  Massive PE causes death by cardiovascular failure, not respiratory failure  Emboli obstruct blood flow resulting in  Alveolar deadspace  Bronchoconstriction  Decreased surfactant production  Hypoxemia  Pulmonary hypertension  Shock (saddle embolus)

11. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.11 Clinical Features  No specific signs or symptoms  Anticoagulation is started on suspicion of PE & stopped only when PE is ruled out  Most common symptom is dyspnea

12. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Clinical Features (cont.) 12

13. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.13 What are the most common symptoms associated with PE?

14. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Clinical Features: Chest Film  Rules out other life-threatening conditions  Radiograph is abnormal in 80% of cases  Enlargement of right pulmonary artery (66%)  Elevation of diaphragm (61%)  Cardiomegaly (55%)  Small pleural effusion (50%)  Patchy or rounded infiltrates next to pleural surface are less common but characteristic of PE 14

15. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Clinical Features: ECG & ABGs  ECG rules out other life-threatening conditions  ECG often abnormal but nonspecific  Tachycardia, ST-segment depression most common  ABG findings most commonly show hypoxemia & hypocapnia  15% to 25% of patients have PO 2 >80 mm Hg 15

16. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Clinical Features: D-dimers  Sensitivity of 97% to 100% for PE  Specificity of 39%, so its use with comorbidities is limited  Level <500 mg/L rules out PE (98%) 16

17. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.17 Diagnosis of DVT  Testing for lower extremity DVT  Venography Standard diagnostic tool Injection of dye  Impedance plethysmography Noninvasive, sensitive, & specific  Compression ultrasonography Noninvasive, sensitive, & specific Test of choice for diagnosis of DVT

18. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Diagnosis of DVT (cont.) 18

19. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.19 Diagnosis of PE  Three tests available 1. V/Q scan 2. Helical/Spiral CTA 3. Pulmonary angiography

20. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.20 The most commonly used (definitive) test for diagnosing a PE is:

21. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Diagnosis of PE: V/Q Scan  Ventilation scan: Radioactive gas inhaled  Perfusion scan: IV push of radioisotope- tagged albumin  Gamma radiation produced by radioisotopes show distribution of blood flow & ventilation  Areas with blood flow or ventilation scan “hot”  Areas with ventilation (hot) but no perfusion (cold) suggest presence of PE 21..

22. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.22 Diagnosis of PE: Helical/Spiral CTA  Principal diagnostic tool when used with IV contrast  Equal to scan if combined with D-dimer  Generally unable to detect smaller PE  Advantage of helical/spiral CTA is its ability to provide alternate diagnoses V/Q..

23. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Diagnosis of PE: Helical/Spiral CTA (cont.) 23

24. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Diagnosis of PE: Helical/Spiral CTA (cont.) 24

25. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.25 Diagnosis of PE: Pulmonary Angiography  Used if scan & spiral CT fail to identify PE  Low risk-to-benefit ratio justifies use of procedure  Catheter is threaded so tip passes through right heart & into pulmonary artery  Radiopaque dye is injected V/Q..

26. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.26 Diagnosis of PE: Pulmonary Angiography (cont.)  Fluoroscope monitors progress of dye  Abnormalities include filling defects & abrupt ending of arteries

27. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.27 Treatment: Prophylaxis of DVT  High mortality justifies prophylactic treatment  Moderate- to high-risk patients include those  Undergoing joint replacement  With acute spinal injury or ischemic stroke  With myocardial infarction or heart failure  Who are MICU patients (i.e., pneumonia)  Treatment is anticoagulant therapy  Heparin or fondaparinux is most commonly used

28. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Management of DVT  Heparin is standard therapy  Immediate action  Does not lyse existing clots but prevents clot growth & formation  Thrombolytic agents  Streptokinase, urokinase, TPA  Actually lyse or destroy PE  Not routinely used  High risk of limb gangrene  Risks & benefits not well established 28

29. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.29 Management of PE  Similar regimen to DVT  First-line heparin followed by oral coumarin  Supportive measures include  Oxygen therapy  Analgesia  Hypotension & shock are treated with vasopressors & fluids  In persistent hypotension due to massive PE, thrombolytics are indicated

30. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Pulmonary Hypertension  Pulmonary arterial hypertension (PAH),  Mean pulmonary artery pressure (MPAP) >25 mm Hg at rest OR MPAP >30 mm Hg with exercise, with increased pulmonary vascular resistance (PVR) & normal left ventricular function  Associated with congenital heart disease, collagen vascular disease, liver cirrhosis, etc  Idiopathic pulmonary arterial hypertension (IPAH) if no identifiable cause is found 30

31. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.31 Pathogenesis: IPAH  Development of IPAH  Genetic predisposition probably required  Follows insult to arterial endothelium  Damage results in vasoconstriction May be caused by abnormal transport of potassium & calcium

32. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.32 Epidemiology: IPAH  3 times more common in women than men  7% of cases are familial  Most common between ages 20 & 50 years  As only 33% of patients are alive in 5 years, it is important to identify & aggressively treat this disorder

33. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.33 Clinical Features: Symptoms of IPAH  Symptoms are vague, so misdiagnosis is common  Initial symptom: dyspnea (60%)  Angina (50%)  Syncope (8%)  Other symptoms include Cough, hemoptysis, hoarseness, & Reynaud’s phenomenon

34. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Clinical Features: Symptoms of IPAH (cont.) 34

35. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.35 Management of Pulmonary Hypertension  Supplemental oxygen (SaO 2 >90%)  Anticoagulation with coumarin  Adjust to keep INR ~2  Vasodilators (calcium channel blockers)  May use digoxin & diuretics to manage side effects  Nitric oxide is preferred Very short half life Does not affect cardiac output Enhances V/Q mismatching

36. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Management of Pulmonary Hypertension (Cont.)  Prostanoids is increasingly used as substitute for inhaled nitric oxide  Epoprostenol  Treprostinil  Iloprost  Surgical Therapy  Atrial Septostomy  Lung transplantation is option for severe hypertension 36

37. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.37 Pulmonary Hypertension in COPD  ~50% of elderly with COPD have significant pulmonary hypertension  Alveolar hypoxia causes vasoconstriction & eventually medial hypertrophy, fibrosis, & lumen narrowing  Leads to hypertension  Severity of COPD correlates with severity of hypertension  Long term oxygen therapy is only treatment that improves survival among this patient population

38. Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.38 The main mechanism for PHTN in COPD patients is: