Overview of Pulmonary Vascular Disease

Architecture of Pulmonary Vasculature

preacinar arteries: accompany the airways to the level of the terminal bronchiole; intra-acinar aa are more distal

hilum - 2000 m m Þ elastic walls

2000 - 500 m m Þ muscular and elastic walls

140 - 500 m m Þ entirely muscular walls

30 - 150 m m Þ transition to non-muscular arteries

generally: preacinar aa–muscular/elastic; respiratory bronchiolar and acinar aa–muscular; alveolar wall aa–non-muscular

Pulmonary Embolism

Definitions:

embolus: originates at one site, travels intravascularly to point of impact (90% originate in deep leg veins)

thromboembolus: term usually used because it is difficult to distinguish a thrombus from an embolus

Epidemiology: pulmonary embolism is the most common and most significant form of pulmonary vascular disease

3^rd most common cause of death in the US; sole or contributing cause in 5-15% of adult deaths in acute hospitals
found in 40-50% of patients at autopsy

Pathogenesis – saddle embolus: cast of the deep veins that obstructs the RV outflow tract and both main pulmonary aa

cardiovascular collapse: can follow submassive embolum when histamine, serotonin and other substances released by platelets cause reflex bronchial and bronchiolar constriction Þ Ý V/Q mismatch; rarely occurs with <40% obstruction

insidious pulmonary HTN or cor pulmonale can result from emboli to more peripheral pulmonary aa

Organization of Emboli: sequence of changes after impaction occurs – allows for dating of the embolus

1-3 days – little reaction between embolus and vascular endothelium
3-8 days – endothelium has overgrown the clot, and endothelial cells have migrated into the embolus
8-10 days – fibroblasts, hemosiderin-filled macrophages, capillaries transversing the clot
3-4 wks – formation of collagen fibers in clot

final organization may have several appearances: it may be an eccentric intimal fibrous plaque within the pulmonary artery, or it may be recanalized; if recanalized lumens are large, it appears as a fibrous intravascular web

Healing of Infarction: acute ischemic necrosis occurs in 10% of embolus patients, patients with LV failure are at risk

extensive collateral flow in the lung is protective and is the reason why it is not more than 10%

progression: initially, there is congestion of capillaries distal to obstruction, due to intrapulmonary collateral flow; if collateral flow is insufficient, ischemic damage causes leakage of blood into airspaces (this transient pulmonary hemorrhage is called the stage of incipient infarction and represents a stage where necrosis is still reversible); if ischemia persists, necrosis continues, and a scar eventually forms

Prognosis: depends on the size Þ death due solely to obstruction occurs when >70% of pulmonary flow is blocked

Other Types of Emboli:

bone marrow: often follow closed-chest cardiac massage

fat emboli: often occlude small pulmonary arteries following trauma; produce symptoms of respiratory failure

tumor embolization: may induce thrombosis or endarteritis obliterans

foreign material: from degenerating intravascular prosthetics or catheters (usually insignificant); filler substances with injectable drugs can induce a granulomatous reaction

Pulmonary Hypertension

(1) Hypoxia-Induced Pulmonary HTN –hypoxiaÞ pulmonary vasoconstriction in an attempt to shunt blood away from underventilated areas; chronic hypoxia Þ hypertrophy of smooth muscle in all pulmonary vessels, even non-muscular

this is the primary mechanism of pulmonary hypertension in altitude exposure, hypoventilation, cystic fibrosis, COPD

(2) Pulmonary Hypertension Associated with an Anatomic Left-Right Shunt

in patients with congenital heart disease, pulmonary HTN starts early, and leads to mortality if the defect is uncorrected

Pathogenesis – the left-right shunt leads to increased pulmonary pressures

initially there is proliferation and hypertrophy of smooth muscle in all vessels (same as in hypoxic state)

chronic Ý pressure Þ endothelial proliferation and then concentric, laminar, intimal fibrosis (may occlude lumen)

fibrinoid necrosis may follow and is due to intense spastic contraction of medial smooth muscle

plexiform and dilatation lesions: probably begins as focal arteritis with thrombosis and recanalization; ends up as a complex small vascular channel in an aneurysmally dilated arterial segment with dilation distally

Prognosis: following surgical correction of the lesion, prognosis depends mostly on the severity of the pulmonary HTN

arteritis or plexiform lesions predicts a poor prognosis

(3) Pulmonary Edema and Pulmonary Venous Hypertension

fluid can enter the lung via Starling forces at the level of the capillary, arteriolar or small venule
tight junctions in the alveolar epithelium restrict fluid transport, so fluid in the intravascular space drains to lymphatics
lymphatics run along the bronchovascular structure and in the visceral pleura and drain into systemic veins

High Pressure Edema: usually secondary to LV failure; grossly, the lungs are heavy, dark blue-red with a frothy fluid;

interlobular septa are widened and this shows up as Kerley B lines on CXR
early changes: interstitial edema (perivascular cuffing - clear area around vessels and bronchi), dilated lymphatics
later: edema spills into alveolar compartment and is seen as eosinophilic material; fibrin and RBCs may be present
gross appearance: brown induration secondary to hemosiderin-laden macrophages (heart failure cells)

interlobular septa are thick and fibrotic; arteries also may be fibrotic
smooth muscle hypertrophy makes veins look like arteries

(4) Permeability Pulmonary Edema – characteristic of ARDS

intravascular hydrostatic pressure is normal, but injury to the endothelium destroys its integrity
manifests as intercellular gaps, cell swelling, membrane blisters, necrosis