Overview

1. Overview the pulmonary circulation consists of arteries, capillaries and veins the major role of the pulmonary circulation is to bring blood in to close proximity to air, so that gas exchange can occur the pulmonary vascular bed receives the entire cardiac output high volume/low pressure system it serves as a filter

4. Pulmonary thromboembolism-a huge problem most common pulmonary disorder among hospitalized patients pulmonary emboli effect at least 650,000 people each year in the US pulmonary emboli account for 100,000 - 200,000 deaths each year

5. Sources of pulmonary emboli thrombi that form in the venous circulation propagate (grow) dislodge and travel through the central veins to the pulmonary arteries femoral, iliac and pelvic veins are the major sources for clinically important pulmonary emboli subclavian veins, dilated right ventricle are less common sources

6. Factors leading to thrombus formation stasis abnormal coagulation enhanced coagulation impaired fibrinolysis tissue injury release of coagulant factors endothelial cell dysfunction

7. Conditions predisposing to venous thromboembolism Surgery - orthopedic procedures (especially hip repair), urologic procedures Trauma Malignancy Pregnancy Oral contraceptives Hormone replacement therapy Myocardial infarction Congestive heart failure Extended bed rest/long periods of travel Nephrotic syndrome Antiphospholipid antibody syndrome Hyperhomocysteinemia Genetic abnormalities in coagulation/fibrinolysis Deficiency of antithrombin III Deficiency of protein C Deficiency of protein S Factor V Leiden mutation (activated protein C resistance) Other genetic processes Sickle cell disease

8. Risk factors in patients with venous thromboembolic disease predisposing factor(s) can eventually be identified in the majority (perhaps > 80%) of patients with venous thromboembolism prior thromboembolism confers significant risk for subsequent events more than one risk factor ? further increased risk over half the episodes in individuals with hereditary coagulation abnormalities occur in the setting of additional stress

9. Circulatory effects of PE clots that lodge in the pulmonary arteries occlude portions of the pulmonary capillary bed the pulmonary capillary bed has enormous reserve with exercise flow can increase 5-fold without increasing pulmonary artery pressure surgical removal of 50% of the pulmonary circulation without increasing PA pressure loss of vascular bed to emboli causes far greater circulatory disruption than expected from the fraction of circulation blocked

10. Circulatory effects of PE emboli lead to pulmonary vasoconstriction and disproportionate increase in pulmonary vascular resistance soluble mediators released from platelets autonomic reflexes large emboli ? ?? pulmonary vascular resistance ? right ventricular failure ? inadequate left ventricular filling ? hypotension and shock smaller, peripheral emboli may result in pulmonary infarction

11. Ventilatory effects of PE

12. Hypoxemia in PE most patients present with moderate hypoxemia- why? increased blood flow through regions of physiologic shunt V/Q mismatch due to perfusion of constricted lung units loss of pulmonary surfactant in areas of pulmonary infarction reduced mixed venous O2 content due to reduced cardiac output

13. Clinical presentation of PE With massive emboli (>50% of the vascular bed obstructed) patients may present with sudden death or circulatory collapse

14. Physical exam signs in PE

15. PFT’s in pulmonary emboli rarely performed in acute PE spirometry and lung volumes generally show little or no abnormality may see mild bronchoconstriction or mild restriction pleuritic pain and splinting can limit study DLCO usually reduced due to obstruction of vascular bed

16. Arterial blood gases in PE moderate hypoxemia with widened A-a O2 gradient not universal increased ventilation leading to ? PCO2 and ? pH exception in patients who can not increase minute ventilation

17. EKG findings in PE Sinus tachycardia Atrial arrhythmias Right bundle branch block - right ventricular overload Classic SIQ3T3 pattern

18. Chest radiograph in PE Normal Low lung volumes Small pleural effusion Atelectasis Decreased vascular markings in an area of lung (Westermark’s sign) Wedge-shaped infiltrate extending to the pleural surface (Hampton’s hump)

19. Diagnostic studies for PE PE is very common and potentially life threatening the presenting symptoms, signs and routine studies are nonspecific the clinician needs a high index of suspicion ideal diagnostic study for PE image pulmonary vascular have high sensitivity and specificity low morbidity inexpensive

20. Pulmonary angiography advantages the “gold standard”; images pulmonary artery very effectively allows measurement of pulmonary artery pressure disadvantages invasive administration of intravenous radiocontrast expensive operator time/availability

21. Radionuclide lung scan perfusion scanning: the patient is injected in a vein with radiolabeled macroaggregated albumin (technetium 99) labeled aggregates are trapped in pulmonary arterioles; retained thoracic radioactivity is imaged with a camera sensitive for decreased flow to areas of the pulmonary vascular bed - not specific

22. Radionuclide lung scan ventilation scanning: the patient inhales a gas mixture containing a different radiotracer (xenon 133) areas of vascular obstruction should have loss of perfusion but preservation of ventilation processes such as pneumonia, COPD, obstructed large airway present as matched ventilation and perfusion defects

23. Radionuclide lung scan - interpretation V/Q scans provide estimates of the probability that a patient has a PE the level of clinical suspicion for PE must be taken into account normal perfusion scan excludes the diagnosis of PE high probability scan with high clinical suspicion gives >95% likelihood of PE multiple segmental unmatched perfusion defects intermediate or indeterminant scans are much less helpful

24. V/Q scans and the likelihood of PE

26. Normal Ventilation Scan

27. Normal Perfusion Scan

28. Abnormal Perfusion Scan with Multiple Defects Secondary to Pulmonary Emboli

29. Other noninvasive tests Because most PE originate as lower extremity DVT, tests for lower extremity DVT are useful if positive - may support therapy without invasive studies Doppler ultrasound Impedance plethysmography tests for enhanced clot degradation - if these prove to be sufficiently sensitive, a negative test may greatly decrease the likelihood of thromboembolism D-dimers

30. Diagnostic algorithm History and exam laboratory studies (ABG), CXR and EKG V/Q scan if intermediate, consider noninvasive studies of lower extremities if significant clinical suspicion and neither V/Q nor noninvasive studies are diagnostic, proceed to pulmonary angiogram

31. Helical CT scan for PE high speed CT scanners bolus radiocontrast injection excellent definition of main, lobar and even segmental pulmonary arteries may provide bonus information about the lungs and mediastinal structures

34. Role of helical CT in current practice Likely to be an important addition - a major modality in current practice at U of M positive and negative predictive values in actual use are still being determined national multicenter trial now underway

35. Treatment of pulmonary embolism prevention prophylactic anticoagulants, ambulation, pneumatic compression stockings in patients at high risk of DVT prompt treatment: heparin, heparin, heparin supportive therapy with oxygen, fluids heparin prevents clot formation; does not lyse clot mortality of untreated pulmonary embolism >30% mortality after initiation of heparin <2%

36. Low molecular weight heparin problems with unfractionated heparin short half-life: continuous infusion required variability requiring frequent laboratory studies low molecular weight heparin-(enoxaparin, dalteparin) longer half-life: twice daily subcutaneous injections standard dosing; no requirement for frequent lab monitoring stable patients without great physiologic compromise can be managed at home

37. Long term care of the patient with DVT/PE heparin for 5-7 days longer term anticoagulation with an oral drug warfarin (coumadin) duration of anticoagulation 6 months if reversible cause up to life-long if persistence of predisposing high level risk factors or if recurrent DVT/PE recent data suggests benefit of life-long low dose anticoagulation usual outcome is restoration of normal V/Q and PVR

38. Additional therapeutic modalities for PE thrombolytic agents - “Drano” streptokinase urokinase tissue plasminogen activator embolectomy - “plumber’s helper”

39. Inferior vena cava filter block passage of further clots from legs to lung excellent for patients failing or not tolerating anticoagulation (bleeding problems) increased risk of subsequent deep vein thrombosis work best in conjunction with anticoagulation

41. Pulmonary hypertension the normal pulmonary circulation is a low resistance circuit enormous capacity to recruit unperfused vessels distensible vessels and ready recruitment allow greatly increased flows with exercise without increasing resistance across the pulmonary vascular bed

42. Resistance across a vascular bed Resistance is directly related to the pressure drop across the vascular bed inversely related to the flow through that bed

43. Pulmonary hemodynamics with exercise

44. Pulmonary hypertension

45. Increased pulmonary vascular resistance vasoconstriction chronic hypoxemia: high altitude or chronic respiratory illnesses COPD pulmonary fibrosis obstructive sleep apnea vascular obstruction recurrent/unresolved pulmonary emboli schistosomiasis

46. Increased pulmonary vascular resistance increased pulmonary blood flow (left-to-right shunts) with chronically increased flow there is remodeling of the arteriolar wall destruction of pulmonary vascular bed emphysema pulmonary fibrosis pulmonary vasculitis

47. Primary pulmonary hypertension idiopathic disorder most commonly seen in women 20-45 years old pathological changes in the pulmonary arteriolar wall medial hypertrophy intimal proliferation and fibrosis similar pattern in pulmonary hypertension due to specific causes fenfluamine/dexfenfluramine use for weight loss chronic cocaine use HIV liver disease with portal hypertension

48. Familial primary pulmonary hypertension

49. Lessons from familial PPH At least 10% of PPH is familial Bone morphogenetic protein receptor II mutation in BMPR2 associated with familial PPH member of TGF-ß receptor family a significant portion of patients with sporadic PPH now are found to have mutations in BMPR2 as well

50. Symptoms of pulmonary hypertension symptoms of an underlying disease process may predominate dyspnea on exertion fatigue syncope chest pain peripheral edema

51. Signs of pulmonary hypertension increased pulmonic component of the second heart sound (P2) right ventricular lift/heave elevated jugular venous pulsations distended liver peripheral edema right ventricular S3 gallop what about lung sounds?

52. Studies in patients with pulmonary hypertension ECG: right ventricular hypertrophy CXR: dilated main pulmonary arteries/pruning of peripheral vascular markings ABG: hypoxemia with exertion PFT’s: findings c/w underlying disease; decreased DLCO Echocardiogram Right heart catheterization

53. Diagnostic approach to pulmonary hypertension careful history and exam, serologies for collagen vascular diseases ECG and echocardiogram aggressively identify treatable causes of secondary pulmonary hypertension hypoxemia (at rest or at night, with sleep apnea) chronic thromboembolic disease right heart catheterization ? pulmonary angiography

54. Treatment of pulmonary hypertension treat underlying disease oxygen - minimize hypoxic vasoconstriction long term anticoagulation (even in PPH) vasodilators Calcium channel blockers Prostacyclin Endothelin receptor blockers (Bosentan) transplantation