Introduction

Pulmonary circulation is the system of transportation that shunts de-oxygenated blood from the heart to the lungs to be re-saturated with oxygen before being dispersed into the systemic circulation. Deoxygenated blood from the lower half of the body enters the heart from the inferior vena cava while deoxygenated blood from the upper body is delivered to the heart via the superior vena cava. Both the superior vena cava and inferior vena cava empty blood into the right atrium. Blood flows through the tricuspid valve into the right ventricle. It then flows through the pulmonic valve into the pulmonary artery before being delivered to the lungs. While in the lungs, blood diverges into the numerous pulmonary capillaries where it releases carbon dioxide and is replenished with oxygen. Once fully saturated with oxygen, the blood is transported via the pulmonary vein into the left atrium which pumps blood through the mitral valve and into the left ventricle. With a powerful contraction, the left ventricle expels oxygen-rich blood through the aortic valve and into the aorta: This is the beginning of systemic circulation.[1]

Development

Around fifteen days after fertilization, blood cell vessels begin to form outside of the implanted embryo which creates the initial placenta. This is vital to maintaining fetal life as it provides a mechanism that delivers oxygen and nutrients to the developing baby and discards waste products. By day seventeen, the fetus is forming red blood cell precursors and initial vasculature. Between three and four weeks after conception, the fetal heart develops all four chambers and begins beating on its own distinctly representative of its vitality separate from that of the mother. 

Because the developing fetus uses the placenta to maintain oxygen saturation and exchange waste for nutrients, fetal circulation is designed to transfer blood around the organs not needed while the fetus is in the womb. Therefore, since blood does not need to enter the fetal lungs or liver, three shunts maximize the efficiency of blood flow. The placenta provides the fetus with oxygen-rich blood via the umbilical vein. Once inside the fetus, blood travels through the ductus venosus which directs blood from the umbilical vein around the liver and into the inferior vena cava. A portion of the blood from the inferior vena cava empties into the right atrium and is shunted through the foramen ovale which transfers it directly into the left atrium thus bypassing the right ventricle and the lungs. The remaining blood in the right atrium travels through the tricuspid valve into the right ventricle.[2] Instead of diverting into the lungs, blood in the right ventricle empties into the pulmonary artery which is connected to the aorta by the ductus arteriosus.[3]

Once the baby is delivered and takes his first breath, the high resistance in the lungs that was present during development drops dramatically. Since the baby is no longer reliant on the placenta for oxygenation, the umbilical vessels are ligated: blood can enter the lungs for oxygenation. The oxygen relaxes the pulmonary vessels and causes constriction and eventual closure of the portal shunts. Once these fetal shunts are fully closed, the neonate’s blood flow is identical to that of an adult.[4]

Pathophysiology

In some patients, fetal circulation shunts remain patent after delivery. Usually, patients with an open fetal shunt are asymptomatic and may only have a cardiac murmur upon auscultation. A patent foramen ovale connects the right and left atria and is usually found as an incidental finding on echocardiogram or after a cryptogenic stroke. In patients with a patent foramen ovale, there is a possibility that a thrombus from the lower extremity may bypass the lungs. This can be accomplished when the blood enters the right atrium, flows through the foramen ovale, and empties into the left atrium.[2] The thrombus would be able to travel from the left atrium into systemic circulation where it can, unfortunately, be delivered to the brain causing a thromboembolic cerebrovascular accident (CVA).

The most worrisome complication of pulmonary circulation dysfunction is a pulmonary embolism which usually arises as a deep venous thrombosis (DVT) of the lower extremity. Rarely do DVTs occur without satisfying at least one of the three components of Virchow’s triad: hypercoagulability, endothelial damage, and venous stasis.[5] Certain genetic disorders like factor V Leiden, protein C deficiency, and protein S deficiency along with more common conditions like pregnancy and cancer are related to states of hypercoagulability.[6] Endothelial damage can occur from trauma or surgery, and venous stasis is commonly associated with periods of immobility either from traveling and disability. If the deep venous thrombus is dislodged from the lower extremity, it is pushed by deoxygenated blood back into the heart and then into the lungs where it can lodge into a small pulmonary vessel. If large enough, the clot can cause hemodynamic compromise to areas proceeding it. Automatically, pulmonary vessels in the area of the thrombus vasoconstrict which causes shunting of blood to non-occluded portions of the lung.[5]

Clinical Significance

Classically, a patient with a pulmonary embolism (PE) due to a DVT presents with symptoms of crushing, pleuritic chest pain, chest pressure, or dyspnea with a history of a swollen, painful lower extremity. Upon physical exam, tachycardia is almost always present. In most cases, the chest x-ray is unremarkable, but occasionally, one or both of the classic chest x-ray findings are visible. Westermark's sign is a sharp delineation between the area of perfusion and hypo-perfusion within a vessel indicating an embolism is blocking flow, and Hampton's hump presents as a wedge-shaped, focal opacity in the periphery of the lung.[5]

When clots form in the body, they are continually being reconstructed. Clotting factor XIII is responsible for cross-linking fibrin into a mesh. Upon degradation, plasmin lyses the fibrin bonds and releases the fibrin degradation products called D-dimers. In some cases of suspected pulmonary embolisms, physicians may order blood samples to test a D-dimer. An elevated D-dimer level has high sensitivity but low specificity for a pulmonary embolism. A D-dimer can be elevated in the setting of any hypercoagulable state such as pregnancy, congestive heart failure, systemic lupus erythematosus (SLE), and other chronic diseases, this test is most useful when a pulmonary embolism is suspected in a younger patient with no co-morbidities. The gold standard of diagnosing a PE is computed tomography (CT) angiography. The contrast is given intravenously and will indicate areas of hypoperfusion caused by a thrombus. However, in instances when there is a contraindication to this imaging study such as in the setting of renal failure when contrast dye cannot be given, a pulmonary ventilation/perfusion (V/Q) scan can be performed.[5]

Another potential complication of pulmonary circulation is pulmonary arterial hypertension. Pulmonary arterial hypertension is defined by a mean pulmonary artery pressure of greater than twenty-five millimeters of mercury and pulmonary vascular resistance greater than three millimeters of mercury which is measured via right heart catheterization. Interestingly, pulmonary arterial hypertension can be caused by a variety of circumstances such as obstruction of the pulmonary arteries and arterioles, increased pulmonary vascular resistance, luminal thickening, vascular remodeling, and chronic inflammation.[4]

In pulmonary arterial hypertension, there is an increase in pulmonary vascular resistance which can be caused by the destruction of the pulmonary vasculature, chronic vasoconstriction, endothelial thickening, arteriole smooth muscle hypertrophy, and endothelial wall remodeling. Thromboxane and endothelin-1 are believed to have increased activity which causes enhanced vasoconstriction while prostacyclin and nitric oxide which both function as vasodilators, have decreased efficiency. Because of these, blood vessels are narrowed which causes higher flow rates and thus pressure in the vasculature. However, these cause increased pulmonary vascular resistance which decreases endothelial integrity. The body naturally attempts to heal endothelial damage by sending coagulation factors to the intimal surface of the vessel.[7]

Left-sided heart failure commonly causes pulmonary venous hypertension. The left side of the heart has difficulty maintaining function. Therefore, blood is forced back into the lungs leading to increased pressure in the pulmonary vein. In the case of left-sided heart failure due to valve failure, decreased ejection fraction, or volume overload, blood that should be ejected into systemic circulation backs up into the left ventricle, left atrium, and finally, the pulmonary veins. Increased pulmonary venous pressure can lead to capillary remodeling and elevated capillary permeability causing fluid leakage into the lung bases. The most common cause of this is congestive heart failure due to left heart dysfunction and volume overload.[4]