Chapter 13: Pulmonary diseases of vascular origin

Question 1

More than …% of all pulmonary emboli arise from thrombi within the large deep veins of the legs, most often those that have propagated to involve the popliteal vein and larger veins above it

Answer 1

95

Question 2

What are some influences that predispose to venous thrombosis in the legs? (7 answers)

you should be able to recognize them

Answer 2

(1) prolonged bed rest (particularly with immobilization of the legs); (2) surgery, especially orthopedic surgery on the knee or hip; (3) severe trauma (including burns or multiple fractures); (4) congestive heart failure; (5) in women, the period around parturition or the use of oral contraception pills with high estrogen content; (6) disseminated cancer; and (7) primary disorders of hypercoagulability (e.g., factor V Leiden)

Question 3

Fill in: The pathophysiologic consequences of pulmonary thromboembolism depend largely on the size of the embolus, which in turn dictates the size of the …

Answer 3

occluded pulmonary artery, and the cardiopulmonary status of the patient

Question 4

What are the two important consequences of pulmonary arterial occlusion?

Answer 4

(1) an increase in pulmonary artery pressure from blockage of flow and, possibly, vasospasm caused by neurogenic mechanisms and/or release of mediators (e.g., thromboxane A2, serotonin); and (2) ischemia of the downstream pulmonary parenchyma. Thus, occlusion of a major vessel results in an abrupt increase in pulmonary artery pressure, diminished cardiac output, right-sided heart failure (acute cor pulmonale), and sometimes sudden death

Question 5

What mechanisms can result in hypoxemia when there’s already pulmonary thromboembolism?

Answer 5

• Perfusion of atelectatic lung zones. Alveolar collapse occurs in ischemic areas because of a reduction in surfactant production and because pain associated with embolism leads to reduced movement of the chest wall.
• The decrease in cardiac output causes a widening of the difference in arterial-venous oxygen saturation.
• Right-to-left shunting of blood may occur through a patent foramen ovale, present in 30% of normal individuals.

Question 6

Why does ischemic necrosis only occur in 10% of patients with thromboemboli?

Answer 6

Because the lungs are not only oxygenated by the pulmonary arteries, but also by bronchial arteries and directly from air in the alveoli

Question 7

So how does ischemic necrosis occur?

Answer 7

Only if there is compromise in cardiac function or bronchial circulation, or if the region of the lung at risk is underventilated as a result of underlying pulmonary disease

Question 8

A large embolus may embed in the main pulmonary artery or its major branches or lodge astride the bifurcation as a …

Answer 8

saddle embolus

Question 9

Are small emboli clinically silent?

Answer 9

Yeah (60-80% of all thromboembolisms)

Question 10

What are the clinical features of emboli? (what clinical feature occurs most of the time during an emboli, what is semi-common and what is rare?)

Answer 10

• 60-80%: small/silent
• 5%: death, acute right-sided heart failure or cardiovascular collapse (shock)
• 10-15%: pulmonary infarction (small-medium pulmonary branches)
• <3% ‘showers’ of emboli lead to pulmonary hypertension, chromic right-sided heart failure, pulmonary vascular sclerosis with progessive dyspnea

Question 11

True/false: Emboli usually don’t resolve after the initial acute event. Why?

Answer 11

False, as endogenous fibrinolytic activity often leads to their complete dissolution

Question 12

What the chance of recurrence of patients who’ve had an embolism?

Answer 12

30%

Question 13

What are treatments for an embolism?

Answer 13

Prophylactic therapy may include anti-coagulation, early ambulation for postoperative and postparturient patients, application of elastic stockings, intermittent pneumatic calf compression, and isometric leg exercises for bedridden patients. Those who develop pulmonary embolism are given anti-coagulation therapy. Patients with massive pulmonary embolism who are hemodynamically unstable (shock, acute right heart failure) are candidates for thrombolytic therapy.

Question 14

Can pulmonary emboli that are nonthrombotic occur?

Answer 14

Yes (uncommon, but potential lethal forms such as air, fat and amniotic fluid, IV drugs abuse)

Question 15

What may pulmonary hypertension be caused by?

Answer 15

A decrease in the cross-sectional area of the pulmonary vascular bed or, less commonly, by increased pulmonary vascular blood flow (>25mm Hg at rest)

Question 16

The WHO has classified pulmonary hypertension in 5 groups. What are they?

Answer 16

• Pulmonary arterial hypertension, a diverse collection of disorders that includes heritable forms of pulmonary hypertension and diseases that cause pulmonary hypertension by affecting small pulmonary muscular arterioles; these include connective tissue diseases, human immunodeficiency virus, and congenital heart disease with left to right shunts
• Pulmonary hypertension due to left-sided heart disease, including systolic and diastolic dysfunction and valvular disease
• Pulmonary hypertension due to lung diseases and/or hypoxia, including COPD and interstitial lung disease
• Chronic thromboembolic pulmonary hypertension
• Pulmonary hypertension with unclear or multifactorial mechanisms

Question 17

As can be gathered from this classification, pulmonary hypertension has diverse causes. What are some of the common causes?

Answer 17

• Chronic obstructive or interstitial lung diseases (group 3).
These diseases obliterate alveolar capillaries, increasing pulmonary resistance to blood flow and, secondarily, pulmonary blood pressure.
• Antecedent congenital or acquired heart disease (group 2). Mitral stenosis, for example, causes an increase in left atrial pressure and pulmonary venous pressure that is eventually transmitted to the arterial side of the pulmo- nary vasculature, leading to hypertension.
• Recurrent thromboemboli (group 4). Recurrent pulmonary emboli may cause pulmonary hypertension by reducing the functional cross-sectional area of the pulmonary vascular bed, which in turn leads to an increase in pul- monary vascular resistance.
• Autoimmune diseases (group 1). Several of these diseases (most notably systemic sclerosis) involve the pulmonary vasculature and/or the interstitium, leading to increased vascular resistance and pulmonary hypertension.
• Obstructive sleep apnea (also group 3) is a common dis- order that is associated with obesity and hypoxemia. It is now recognized to be a significant contributor to the development of pulmonary hypertension and cor pulmonale.

Question 18

Primary (genetic) pulmonary hypertension has been seen in proven to play a role in “idiopathic” hypertension. What gene/signaling pathway has shown great insight?

Answer 18

the bone morphogenetic protein (BMP)–signaling pathway. Inactivating germ line mutations in the gene encoding bone morphogenetic protein receptor 2 (BMPR2) are found in 75% of the familial cases of pulmonary hypertension and 25% of sporadic cases. More recently, mutations in other genes that are involved in the BMPR2 pathway also have been identified in affected patients

Question 19

Regardless of their etiology, all forms of pulmonary hypertension are associated with …

Answer 19

medial hypertrophy of the pulmonary muscular and elastic arteries, pulmonary arterial atherosclerosis, and right ventricular hypertrophy.

Question 20

What are the clinical features of pulmonary hypertension?

Answer 20

Pulmonary hypertension produces symptoms when the disease is advanced. The presenting features are usually dyspnea and fatigue, but some patients have anginal chest pain. Over time, respiratory distress, cyano- sis, and right ventricular hypertrophy appear, and death from decompensated cor pulmonale, often with superim- posed thromboembolism and pneumonia, ensues within 2 to 5 years in 80% of patients.

Question 21

True/false: All patients of pulmonary hypertension are treated with diuretics

Answer 21

False, treatment choices depend on the underlying cause.

Illustration: For those with secondary disease, therapy is directed at the trigger (e.g., thromboembolic disease or hypoxemia). A variety of vasodilators have been used with varying success in those with group 1 disease or refractory disease belonging to other groups. Lung transplantation is the definitive treatment for selected patients.

Question 22

What is pulmonary hemorrhage?

Answer 22

a dramatic complication of some interstitial lung disorders

Question 23

What are the three ‘hemorrhage syndromes’?

Answer 23

1) Goodpasture syndrome, (2) idiopathic pulmonary hemosiderosis, and (3) granulomatosis with polyangiitis.

Question 24

What is the good pasture syndrome?

Answer 24

Goodpasture syndrome is an uncommon autoimmune disease in which lung and kidney injury are caused by circulating autoantibodies against certain domains of type IV collagen that are intrinsic to the basement membranes of renal glomeruli and pulmonary alveoli

Question 25

Fill in: More than 80% of patients with granulomatosis and polyangiitis (GPA; formerly Wegener granulomatosis) develop … manifestations at some time in their course

Answer 25

upper-respiratory or pulmonary