Why does the pulmonary artery have higher glucose concentration than the pulmonary vein?

Why does the pulmonary artery have higher glucose concentration than the pulmonary vein?

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If the pulmonary artery have higher glucose concentration than the pulmonary vein, does it mean glucose will be consumed during gas exchange?

That confused me because gas exchange is something like diffusion and shouldn't consume any glucose

Gas exchange doesn't but the cells of the tissue it occurs in do consume glucose, even the cells in the walls of the artery will consume some. The cells in the lungs still need to be fed and only one of those two vessels has flow going into the tissue so it is the one that has to carry that glucose into the tissue.

Role of NO and EDHF-mediated endothelial function in the porcine pulmonary circulation: Comparison between pulmonary artery and vein

To compare electrophysiological measurement of nitric oxide (NO) release and endothelium-derived hyperpolarizing factor (EDHF)-mediated endothelial function in porcine pulmonary arteries and veins.


Isolated pulmonary interlobular arteries (PA) and veins (PV) were obtained from a local slaughterhouse. By using a NO-specific electrode and a conventional intracellular microelectrode, the amount of NO released from endothelial cells and hyperpolarization of smooth muscle cells were investigated. The bradykinin (BK)-induced relaxation in the precontraction by U46619 was examined in the absence or presence of N G -nitro- l -arginine ( l -NNA), indomethacin (INDO) plus oxyhemoglobin (HbO).


The basal release of NO was 7.0 ± 1.2 nmol/L in PA (n = 8) and 5.5 ± 1.6 nmol/L in PV (n = 8, p < 0.01). BK-induced release of NO was 160.4 ± 10.3 nmol/L in PA (n = 8) and 103.0 ± 14.7 nmol/L in PV (n = 8, p < 0.001) with longer releasing duration in PA than in PV (14.3 ± 1.3 vs. 12.1 ± 0.8 min, p < 0.01). BK evoked an endothelium-dependent hyperpolarization and relaxation that were reduced by l -NNA, INDO, and HbO (hyperpolarization: 12.8 ± 1.3 vs. 8.0 ± 1.4 mV in PA, n = 6, p < 0.001 and 8.3 ± 1.4 vs. 3.0 ± 0.8 mV in PV, n = 6, p < 0.001 relaxation: 92.8 ± 3.1% vs. 19.6 ± 11.1% in PA n = 8, p < 0.001 and 70.3 ± 7.9% vs. 6.0 ± 6.8% in PV, n = 8, p < 0.001). Both hyperpolarization (8.0 ± 1.4 vs. 3.0 ± 0.8 mV, p < 0.001) and relaxation (19.6 ± 11.1% vs. 6.0 ± 6.8%, p < 0.01) were greater in PA than in PV.


Both NO and EDHF play an important role in regulation of porcine pulmonary arterial and venous tones. The more significant role of NO and EDHF is revealed in pulmonary arteries than in veins.

Structure of the aorta

The aorta is divided into 5 main sections:

  • Aortic root - This is the base of the aorta where it connects to the heart's pumping chamber. It gives rise to two coronary arteries which are responsible for carrying oxygenated blood to the heart muscles. The two coronary arteries end at the beginning of ascending aorta.
  • Ascending aorta - This section of the aorta begins from the aortic root and ascends upwards to the point where the aorta forms an arch. Due to very little support of the surrounding tissue and handling the complete output volume of the cardiac, it is considered one of the most vulnerable parts of the aorta.
  • Aortic arch - This is the curved section of the aorta. Along with brachiocephalic (aka. innominate), left common carotid and left subcalvian arteries it supplies blood to the upper body including the head.
  • Descending aorta - Beginning from the arch it descends downwards into the body and ends at diaphragm. It supplies oxygenated blood to the spinal cord.
  • Thoracoabdominal aorta - This section begins at the diaphragm and ends at the celiac, superior mesenteric and the visceral vessels.
  • Abdominal aorta – This section begins below the renal arteries and ends at the two iliac arteries. It also contains a small artery named the inferior mesenteric artery. This section supplies blood to the kidneys.

Structure of the Pulmonary Artery

The pulmonary artery is divided into 2 main sections:

  • Pulmonary trunk: Also known as pulmonary artery or main pulmonary artery, this section originates at the right ventricle and further branches into left and right pulmonary arteries.
  • Left and Right Pulmonary arteries: Branching from the pulmonary trunk, the left and right pulmonary arteries supply deoxygenated blood to the left and right lung respectively.


While veins usually carry deoxygenated blood from tissues back to the heart, in this case, pulmonary veins are among the few veins that carry oxygenated blood instead. Oxygenated blood from the lungs is circulated back to the heart through the pulmonary veins that drain into the left atrium. Once blood is pumped from the left atrium through the mitral valve into the left ventricle, this oxygenated blood will then be pumped from the left ventricle through the aortic valve to the rest of the body’s organs and tissues through the aorta.

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Deoxygenated blood that has circulated through the system will be collected from the superior vena cava and inferior vena cava, which drain into the right atrium of the heart. Once deoxygenated blood is pumped from the right atrium through the tricuspid valve into the right ventricle, contraction of the right ventricle will push blood through the pulmonic valve into the pulmonary artery that will carry deoxygenated blood to the lungs. Within the lungs, the blood passes through capillaries adjacent to alveoli and becomes oxygenated through respiration (breathing). Branches of the pulmonary artery travel closely alongside the bronchial tree on their way to the alveoli. However, the bronchial tree itself is supplied by the bronchial artery, which arises from the aorta and carries systemic blood. Each alveolus is surrounded by a nest of blood capillaries that are supplied by small branches of the pulmonary artery.

Check the following study units to learn more about the pulmonary arteries and veins and their relation to the hilum of the lungs and the heart.

In summary, the pulmonary circuit begins with the pulmonary trunk, which is a large vessel that ascends diagonally from the right ventricle and branches into the right and left pulmonary arteries. As the circuit approaches the lung, the right pulmonary artery branches into two arteries and both branches enter the lung at a medial indentation called the hilum of the lung. The upper branch is the superior lobar artery, which feeds into the superior lobe of the lung. The lower branch divides again within the lung to form the middle lobar and inferior lobar arteries that supply the lower 2 lobes of the lung since there are 3 lobes of the right lung. The left pulmonary artery is more variable in number and gives off several superior lobar arteries that feed into the superior lobe before entering the hilum of the lung to branch off into inferior lobar arteries that feed the left lower lung lobe.

Are you curious to find out more about the anatomy of the pulmonary arteries and veins and a condition called pulmonary embolism?

Two sides of the heart pump blood through two different circulations. Pulmonary circulation involves movement of blood from the right ventricles to the lungs.

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This takes place in order for the patient with leukemia can be suitable to receive new bone marrow. Treatment falls under the specifications of a transplant.

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The author focuses on the coronary heart disease. His article starts by giving an introduction about the heart’s structure and function. It explains briefly .

Erythrocytes, also known as RBCs, are a major component of O2 delivery to the brain. The primary function of red blood cells is to transport respiratory gase.

•Immunoglobulins- these are antibodies which is used as a protection against infections. Functions of blood •Transport: Blood is the primary means of transp.

The molecular weight of bovine hemoglobin is about 64.5 kDa. In terms of its structure, hemoglobin is a tetramer consisting of 2 pairs of polypeptide chains .

Bacteria that respire by the use of oxygen, otherwise known as aerobic respiration, produce enzyme or “catalase”. This protects the bacteria from the harmful.

The heart uses the help of blood vessels and capillaries to deliver blood from left ventricle to the body with the help of aorta and atria diastole cardiac c.


Pulmonary hypertension (PH) is a feature of a variety of diseases and continues to harbor high morbidity and mortality. The main consequence of PH is right-sided heart failure which causes a complex clinical syndrome affecting multiple organ systems including left heart, brain, kidneys, liver, gastrointestinal tract, skeletal muscle, as well as the endocrine, immune, and autonomic systems. Interorgan crosstalk and interdependent mechanisms include hemodynamic consequences such as reduced organ perfusion and congestion as well as maladaptive neurohormonal activation, oxidative stress, hormonal imbalance, and abnormal immune cell signaling. These mechanisms, which may occur in acute, chronic, or acute-on-chronic settings, are common and precipitate adverse functional and structural changes in multiple organs which contribute to increased morbidity and mortality. While the systemic character of PH and right-sided heart failure is often neglected or underestimated, such consequences place additional burden on patients and may represent treatable traits in addition to targeted therapy of PH and underlying causes. Here, we highlight the current state-of-the-art understanding of the systemic consequences of PH and right-sided heart failure on multiple organ systems, focusing on self-perpetuating pathophysiological mechanisms, aspects of increased susceptibility of organ damage, and their reciprocal impact on the course of the disease.

Pulmonary hypertension (PH) in its various forms affects ≈1% of the global population, and up to 10% of individuals >65 years of age. 1 PH is defined by a mean pulmonary artery pressure ≥25 mm Hg at rest, although a lower threshold (>20 mm Hg) was recently proposed during the 6 th World Symposium on PH. 2 Based on left-sided filling pressure, measured as pulmonary arterial wedge pressure (PAWP) or left ventricular end-diastolic pressure, PH is subclassified into pre- (pulmonary arterial wedge pressure/left ventricular end-diastolic pressure ≤15 mm Hg) and postcapillary PH (pulmonary arterial wedge pressure/left ventricular end-diastolic pressure >15 mm Hg). 2,3 PH occurs as a common consequence of multiple underlying diseases including pulmonary vascular disease and thromboembolic disease, but is most commonly associated with left-sided heart disease and chronic lung disease, particularly in elderly individuals. 1–3 The clinical classification of PH distinguishes 5 groups: (1) Pulmonary arterial hypertension (PAH) (2) PH caused by left heart disease (LHD) (3) PH caused by lung disease or hypoxia (4) Chronic thromboembolic PH (CTEPH) and (5) PH with unclear or multifactorial mechanisms. 2 Although these entities are distinct from a pathogenetic perspective, they may all cause severe PH, representing an increased right ventricular (RV) afterload and, as a common final path, eventually lead to right-sided heart failure (HF), which aggravates symptoms and results in a high mortality risk. 3 Strikingly, deterioration in RV structure and function greatly exceeded corresponding changes in the left ventricle (LV) during long-term follow-up in patients with left-sided HF with preserved ejection fraction. 4 In addition, PH and RV dysfunction are often accompanied by hypoxemia, which can have multiple, often co-existing causes, and affect multiple organ systems (Figure 1). Interorgan crosstalk involves circulating pro-inflammatory cytokines that act locally, but may also affect other organ systems distant from their origin (Figure 2). While the systemic character of PH and right-sided HF is often neglected or underestimated, such consequences place additional burden to patients and may represent treatable traits in addition to targeted therapy of PH and underlying causes. Here, we highlight the systemic consequences of PH and right-sided HF in multiple organ systems.

Figure 1. Systemic consequences of pulmonary hypertension and right heart failure in multiple organ systems.

Figure 2. Systemic consequences of pulmonary hypertension (PH) and right-sided heart failure: Interdependent mechanisms, systemic inflammation, and interorgan cross-talk. In PH or pulmonary arterial hypertension (PAH), elevated pulmonary artery pressure and pulmonary vascular resistance (PVR)—representing an increased right ventricle (RV) afterload—lead to right heart strain and failure, which in turn also affects left heart function. Both impaired perfusion caused by systemic low output and systemic congestion caused by impaired RV function cause insult to numerous organ systems. This leads to local liberation of soluble proinflammatory mediators, and thus initiation of inflammatory cascades. This scenario is associated with systemic inflammation, where locally liberated circulating proinflammatory cytokines act in a paracrine fashion, but also affect other targets. 28,35 CVP indicates central venous pressure GI, gastrointestinal LMCS, left main compression syndrome PA, pulmonary artery and RAP, right atrial pressure.

Left Ventricle

Eccentric remodeling and contractile dysfunction of the right heart in patients with PH or pulmonary arterial hypertension (PAH) have an important impact on the LV, as they may result in impairment of LV geometry, structure, and function (Figure 3). Given the interdependency of the left and right sides of the heart, which is determined by shared myocardium (septum), pericardial restraint and the serial nature of the circulatory system, right ventricular strain directly affects the left ventricle. Increases in RV size and pressure cause mechanical septal leftward shift leading to LV compression, 5 which is visualized by paradoxical septal movement, a “D-shaped” left ventricle, and an increased LV eccentricity index. A low stroke volume and cardiac output from RV dysfunction may contribute to underfilling of the LV, particularly during exercise. 6 Diastolic ventricular interaction is also important in PH/RV failure, because right heart overload and pericardial restraint may cause elevation in left heart filling pressures even when LV preload is reduced and the LV is underfilled. 7,8

Figure 3. Impact of pulmonary hypertension and right heart failure on the left heart. Right ventricle (RV)–left ventricle (LV) interaction is markedly influenced by volume management, where IV fluid in the setting of marked LV compression leads to increased RV wall tension and further deterioration, whereas volume reduction under careful monitoring decompresses the RV, leads to improved RV function, and allows better filling of the LV, improved coronary perfusion, and increased cardiac output.

Because the heart muscle constantly adapts to its demands, reduced work load and chronic underutilization of the LV lead to deconditioning and atrophic remodeling in PAH, characterized by reductions of LV end-diastolic volume and LV mass by ≈10–20% and 5–15%, respectively, and reductions in LV systolic strain, stroke volume and ejection fraction. 8–10

At the cellular and molecular level, the LV myocardium of patients with end-stage PAH displays cardiomyocyte atrophy and contractile dysfunction, as indicated by substantial reductions in the cross-sectional area and the maximal force-generating capacity of cardiac myocytes by ≈30% and ≈25%, respectively, as well as lower cellular content of the contractile protein myosin, impaired phosphorylation of sarcomeric proteins (cardiac troponin I, myosin-binding protein C), reduced number of available myosin-based cross-bridges, and a leftward shift in the force [Ca 2+ ] relationship. 11 The latter indicates an increase in the [Ca 2+ ] sensitivity of force generation and may be viewed as a compensatory mechanism for the reduced force-generating capacity, 11 but may also provide an explanation for impaired LV diastolic function in PAH. 8

The importance of an atrophic and malfunctioning LV becomes particularly evident in the context of lung transplantation in end-stage PAH, where increased postoperative filling and the inability to handle a normalized preload may lead to LV failure. 12 This temporary phenomenon may effectively be bridged by veno-arterial extracorporeal membrane oxygenation after lung transplantation to allow the LV to adapt to normalized hemodynamics. 12

In addition to its consequences on LV myocardium, severe PH may also affect coronary perfusion. Because of the topographical proximity, pulmonary artery dilation may occasionally cause compression of the left main coronary artery (left main compression syndrome), and may trigger myocardial ischemia and arrhythmias. 13 Indeed, a significant number of PAH patients die from sudden death, and a pulmonary artery diameter ≥48 mm was associated with a 7.5-fold increased risk for sudden unexplained death in patients with severe PAH or CTEPH. 14 As improved treatment options have led to prolonged survival in PAH, physicians should be alert for such emerging risk factors in long-term survivors.


The liver of patients with PH and RV failure may be exposed to decreased arterial perfusion, hypoxemia, and venous congestion. 15 Relatively little research has been done on liver dysfunction in patients with PAH, while there is abundant literature on the effects of HF on liver function in patients with underlying LHD. In the aggregate, there is a strong body of evidence suggesting that liver dysfunction in these patients is closely related to right-sided HF rather than to LV dysfunction.

Acute right- or left-sided HF with shock and hepatic hypoperfusion may result in ischemic hepatitis (Figure 4A, right). Its histological hallmark is centri-lobular necrosis. 15 Characteristic laboratory findings are rapid increases in serum amino-transferases (>20 times the upper level of normal) and lactate dehydrogenase. Serum bilirubin is only mildly elevated, except for cases that progress to liver failure or secondary ischemic cholangiopathy. The majority of cases are reversible if the underlying cause is resolved, although progressive liver dysfunction and acute liver failure have been reported. Pre-existing hepatic venous congestion caused by right-sided HF seems to increase the risk of acute ischemic hepatitis. 16

Figure 4. The liver and kidney in pulmonary hypertension and right heart failure.A, Acute ischemic hepatitis and congestive hepatopathy. Right inset, Centrilobular necrosis in ischemic hepatitis (from reference 15 ). Left inset, Chronic hepatic congestion with sinusoidal dilatation and portal fibrosis (from reference 17 ). B, Congestive nephropathy. Right inset, Low perfusion kidney injury caused by hypoperfusion and ischemia, demonstrating fibosis (*), necrotic cells (arrowhead), and intraluminal debris (from reference 30 ). Left inset, Congestive nephropathy, characterized by interstitial edema, swollen tubule cells, and tubular compression (from reference 33 ). ALAT indicates alanine transaminase AP, arterial pressure ASAT, aspartate aminotransferase CVP, central venous pressure LDH, lactic acid dehydrogenase and yGT, gamma-glutamyl transpeptidase.

Chronic congestive hepatopathy has commonly been described in patients with underlying LHD, but its degree is not related to LV dysfunction but to the presence of PH and elevated right-sided filling pressures. 17,18 Chronic hepatic congestion may result in liver fibrosis or, occasionally, in cardiac cirrhosis. 19 In patients with congestive HF, the extent of hepatic fibrosis was associated with right atrial pressure, right atrial dilatation, and right ventricular dilatation (Figure 4A, left). 17 The authors concluded that hepatic fibrosis correlated with the degree of right-sided HF, irrespective of the cause. Consistently, in patients with precapillary PH, elevated levels of liver fibrosis marker, P4NP 7S (7S domain of collagen type IV), were associated with higher central venous pressure, right-sided volume overload, and mortality. 20

Patients who develop congestive hepatopathy are typically those with severe and prolonged right-sided HF. Presenting features include signs of systemic venous congestion such as enlarged and pulsating jugular veins and edema, as well as jaundice and ascites. Larger amounts of ascites in the absence of edema may indicate cardiac cirrhosis. Laboratory findings include elevated levels of yGT (y-glutamyl-transpeptidase), ALP (alkaline phosphatase) and bilirubin, and normal or mildly elevated serum aminotransferases. 15,19 Impaired synthetic liver function with reduced serum albumin may be encountered in advanced cases, 21 and hepatic drug metabolism may also be impaired. 15 Characteristic changes in hepatic blood flow patterns may be observed with ultrasound. Taniguchi et al recently demonstrated that liver stiffness, as assessed by elastography using a Fibroscan device correlated with variables indicating right-sided HF, was associated to the clinical severity of HF, and predicted clinical outcomes. 22 Elevated serum bilirubin levels are associated with an increased mortality risk in patients with PAH, at least in univariate analyses. 23,24


Elevated serum creatinine concentrations and/or a low estimated glomerular filtration rate are present in 12% to 29% of PAH patients and are associated with poor outcome. 25,26 In the REVEAL registry (Registry to Evaluate the Early and Long-term Pulmonary Arterial Hypertension Disease Management), a large US based registry of PAH patients, an association between renal insufficiency and death was found in both univariate and multivariate analyses. 24 Even slight abnormalities are clinically significant, 25 with both the absolute value and a ≥10% decline in estimated glomerular filtration rate from baseline over ≥1 year associated with an increased risk of death in the REVEAL registry. 27

In PH, the heart aims to accommodate increased PVR by balancing pre- and afterload, which may be accomplished by neurohormonal activation (eg, arginine, vasopressin, endothelin-1). This however leads to water and salt retention, venous congestion, and reduced cardiac output. In states of diminished cardiac output or impaired contractile reserve, renal dysfunction is traditionally thought to occur secondary to renal hypoperfusion (Figure 4B, right). 28,29 Accordingly, markers of low cardiac output or tissue hypoxia, including uric acid, correlate with disease severity and mortality in PAH. 31 However, chronic venous congestion resulting from right-sided HF also appears to play a central role in distant organ malfunction including acute and chronic kidney injury, and central venous pressure has been found to be one of the most important hemodynamic determinants of worsening renal function in both PAH and HF. 26,32 In PAH patients, both decreased cardiac index and increased right atrial pressure were independent determinants of reduced estimated glomerular filtration rate over time. 26

Renal congestion results from backward transmission of elevated central venous pressure as a consequence of right-sided HF and is characterized by renal edema, increased interstitial pressure, tubular compression, and intracapsular tamponade, which may further aggravate back pressure and thus decrease renal perfusion pressure and glomerular filtration rate (Figure 4B, left). A recent Doppler ultrasonography study in HF patients revealed that intrarenal venous flow patterns, rather than arterial resistance index, related to central venous pressure and strongly correlated with clinical outcomes. 34 Furthermore, activation of venous endothelium acts as a stimulus for release of inflammatory mediators, which in turn may act locally (causing structural glomerular and interstitial damage, sclerosis/fibrosis as well as functional abnormalities such as diminished tubular reabsorption, proteinuria, and retention of salt and water) 28,29 or affect distant organ systems (Figure 2), including the lung. 35

During the course of PH progression, it is likely that repetitive episodes of subclinical acute kidney injury occur, which depict a slow progressive degenerative process and predispose to the development of subsequent chronic kidney disease. 36 Sensitive markers of early kidney injury include L-FABP (L-type fatty acid-binding protein), NGAL (neutrophil gelatinase-associated lipocalin, and KIM-1 (kidney injury molecule-1). 37,38 Even mild proteinuria indicates endothelial dysfunction, and tubulo-interstitial fibrosis best correlates with the development of chronic kidney disease.

In the setting of decompensated PH, RV failure, and acute kidney injury, deterioration of either organ function may result in a vicious circle leading to refractory congestive right-sided HF. Patients with acute-on-chronic renal injury have a narrow window for fluid management of venous congestion and are at high risk of worsening cardiorenal function and death. However, in the setting of acute decompensated HF with worsening renal function, it is important to note that although intensive volume removal initially resulted in worsening of creatinine and a rise in tubular injury biomarkers (NAG, KIM-1, NGAL), renal function recovery over time was superior, suggesting that the benefits of decongestion may outweigh any modest or transient increases in serum creatinine or tubular injury markers. 39

Notably, there is crosstalk between the pulmonary vasculature, the (right) heart, and the kidney. 28 While the kidney is dependent on blood flow and perfusion pressure generated by the heart, the heart is directly dependent on the regulation of fluid homeostasis and the body´s salt and water content by the kidney. Furthermore, renal dysfunction itself may aggravate PH, because circulatory factors have been implicated in the pathogenesis of pulmonary inflammation after renal injury, which may aggravate pathomechanisms of PH. 28

Few data are available on the impact of targeted PAH therapies on renal function. In a post hoc analysis of the SUPER-1 study (Sildenafil Use in Pulmonary Arterial Hypertension-1), treatment with the phosphodiesterase type 5 inhibitor sildenafil was associated with improved kidney function. 40 The impact of other targeted PAH therapies on renal function merits further investigation.

Gut and Bowel

Altered gut permeability resulting in bacterial translocation and endotoxinemia was described in patients with congestive HF and has been linked to impaired arterial perfusion and venous congestion. 41 Similar mechanisms are to be expected in patients with PH and right-sided HF. Mechanistically, bacterial translocation occurs when the edematous or ischemic gut mucosa loses its barrier function. Bacteria and toxins penetrate through the intestinal epithelium and are carried by lymphatic drainage to mesenteric lymph nodes from where they reach other organs and the blood stream. 42

Niebauer and coworkers have shown that in patients with congestive HF and edema, elevated endotoxin levels could be normalized with diuretic treatment, 43 suggesting that venous congestion of the bowel wall was the main cause of a leaky bowel. Bacterial translocation from the bowel may also explain, at least partly, why nonpneumogenic sepsis and sepsis-like illness without documented bacteremia were relatively frequent causes (15%) of intensive care unit admissions in patients with PAH. 44 Furthermore, C-reactive protein levels were elevated in the vast majority of PAH patients admitted to the intensive care unit, in particular in patients who did not survive. 44 Although speculative, it is possible that a leaky bowel may have been a main source of inflammation in these patients.

Recently, Ranchoux et al proposed a gut-lung connection in PAH where intestinal leakiness and endotoxinemia, potentially occurring as a consequence of right-sided HF and intestinal congestion, may promote exacerbated inflammation and pulmonary vascular remodeling, 45 thus contributing to a self-perpetuating process. Specifically, they showed that lipopolysaccharide translocation from gut lumen to bloodstream activated pulmonary and systemic TLR4 (Toll-like receptor 4), the main receptor for lipopolysaccharide, which was associated with increased levels of soluble CD14 (cluster of differentiation 14 lipopolysaccharide-binding protein), a marker of macrophage activation. The blood levels of lipopolysaccharide, TLR4 and soluble CD14 were markedly elevated in patients with idiopathic PAH (IPAH) or heritable PAH, supporting that both bacterial translocation and macrophage activation occur in PAH. 45 Furthermore, lipopolysaccharide serum levels were substantially lower in treated versus untreated PAH patients, and TLR4 deficiency completely protected against experimental PH. Interference with gut microbiota or TLR4 may thus be effective in disrupting this vicious circle.

Bowel dysfunction in patients with HF has been linked to the development of cachexia, which again seems to be closely associated with the presence of RV rather than LV dysfunction. 46 In a recent study among patients with left-sided HF, the presence of cachexia was related to bowel wall thickness, elevated right atrial pressures and RV dysfunction, but not LV ejection fraction. 47 Bowel wall thickness, in turn, correlated with C-reactive protein levels, suggesting a link between elevated right-sided filling pressures, bowel congestion, and systemic inflammation. In patients with intestinal congestion and cachexia, gut microbiota may also contribute to progression of the HF syndrome and mortality. 48 While data on cachexia have been generated primarily from patients with PH-LHD, similar mechanisms likely apply to other forms of PH.

Iron Homeostasis

Iron deficiency (ID) is common in patients with idiopathic PAH, with prevalence ranging from 30% to 63%, 49,50 and occurring independently of anticoagulation status. In a study where the prevalence of ID was 30%, patients with mutations in BMPR2 (bone morphogenetic protein receptor type 2) appeared to have the highest point prevalence of ID at 60%. 50 In the same study, patients with CTEPH had lower point prevalence of ID than idiopathic PAH despite higher rates of anticoagulation and being older. 50 While not entirely consistent across studies, ID appears to be associated with worse World Health Organization Functional Class, lower exercise capacity, worse hemodynamics, and higher serum NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels in idiopathic PAH. 49,50 In addition, ID (defined as soluble transferrin receptor levels >28.1 nmol/l or by the soluble transferrin receptor index) was associated with increased mortality. 49

Enteric iron absorption is negatively regulated by hepcidin, which is released from the liver in the presence of iron loading. Hepcidin levels were inappropriately elevated in patients with IPAH, which may contribute to ID 49 and explain the poor response to oral iron replacement, through presumed decreased gut absorption. 51 The inappropriate elevation of hepcidin in idiopathic PAH appears to be independent of IL-6. 49 When BMPR-2 is knocked down in HepG2 cells (hepatoma cell line G2), BMP-6–mediated hepcidin expression is further increased, 49 possibly providing a connection between altered BMP signaling in PAH and ID.

It has not yet been established whether ID is simply a bystander (risk marker) or disease-modifying risk factor in PAH. In humans, there are fairly compelling data that iron is a significant regulator of pulmonary vascular tone. Otherwise healthy individuals with ID have exaggerated hypoxic vasoconstrictive response which can be corrected with intravenous iron replacement. 52 In addition to its effects on pulmonary vascular tone, ID may also affect vascular remodeling, although this is less clear.

ID may thus be mimicking a pseudohypoxic stimulus to the pulmonary vasculature. Iron is a cofactor in the prolyl hydroxylation of hypoxia-inducible factor (HIF) 1α and 2α, which targets it for ubiquitination and degradation. Thus, ID leads to stabilization of HIFs and increased HIF-dependent transcription. Conversely, in the presence of ID, depletion of iron-sulphur clusters allows iron-regulatory protein-1 to bind to cis-regulatory iron response elements, leading to translational repression of HIF2α, which prevents expression of erythropoietin. 53 In addition to direct effects on the pulmonary vasculature, ID is associated with reduced myoglobin, impaired mitochondrial oxidative capacity, and anemia, limiting the aerobic capacity of muscle tissue, and may also affect myocardial metabolic substrate use through mitochondrial dysfunction. 54

Two open-label studies of intravenous iron replacement in patients with ID and PAH have demonstrated improved exercise capacity and delayed time to the anaerobic threshold. 55,56 No changes were seen in right ventricular function, yet skeletal muscle biopsy samples showed improved oxygen handling through increased myoglobin and mitochondrial oxidative capacity, suggesting that the benefits of iron repletion may not be acting only through changes in central cardiopulmonary hemodynamics. 56

Skeletal Muscles and Diaphragm

Reduced cardiac function with impaired oxygen delivery to skeletal muscles during exercise is the predominant mechanism by which exercise is impaired in PH. Yet, skeletal muscle function, including that of respiratory muscles, 57 may be affected in PAH independent of cardiac output. Maximal volitional and nonvolitional strength of the skeletal muscle is not dependent upon blood flow and is therefore an independent indicator of muscle function. In PAH, both the quadriceps and inspiratory muscles have impaired strength which correlates with exercise capacity.

Studies investigating the mechanisms involved have yielded inconsistent findings, although overall, there is a tendency towards decreased maximal tension, but with variable findings of muscle fiber size, fiber subtype, and capillary density. 57 Diaphragm samples obtained at the time of pulmonary endarterectomy in patients with CTEPH showed that slow twitch fibers displayed decreased maximal force generation, which correlated with maximal inspiratory pressure. 58 No difference was seen in fiber cross-sectional area between patients and controls undergoing elective surgery, but calcium sensitivity of force generation was reduced in fast twitch fibers, which could be restored with troponin activation.

Mechanisms leading to muscle dysfunction are not fully understood but may be both systemic and local in origin. Circulatory pro-inflammatory cytokines are postulated to lead to muscle fiber atrophy and impaired contractile function through proteolysis. 59 More specifically, increased circulating GDF-15 (growth differentiation factor-15) correlates with muscle fiber diameter and strength, which may be mediated through phosphorylation of TAK1 (TGFβ-activated kinase 1) and reversed by TAK1 inhibition. 60 Reduced physical activity in PH but increased ventilatory demand may be expected to lead to relative protection of respiratory muscle function compared with peripheral muscles, but in turn, this may make them more vulnerable because of increased protein turnover and thus susceptible to systemic factors. 57 Deconditioning of peripheral muscles is associated with reductions in capillary density, and systemic factors such as iron deficiency and reduced cardiac output/oxygen delivery further contribute to impaired aerobic capacity of muscle tissue.

Endocrine System

Thyroid Disease

Patients with PAH have a high prevalence of thyroid disease of ≈20%, 61 and thyroid disease is a predictor of poor prognosis in PH. A recent registry analysis of 1756 patients with various forms of PH determined that untreated hypo- or hyperthyroidism measured by thyroid stimulating hormone levels predicted mortality in IPAH patients. 62 Patients with treated thyroid disease had a better survival and reduced free triiodothyroine levels predicted death in PAH and CTEPH patients with untreated thyroid disease. 62 Even subclinical hyper- or hypothyroidism are associated with an increased risk of incident atrial fibrillation, 63 which is detrimental in PH.


The prevalence of hypothyroidism in IPAH is 10% to 24%. 64 Despite data on its association beginning over 2 decades ago, information about the direct relationship of hypothyroidism and the pulmonary circulation remains limited. One observational study of 63 patients with PAH found that ≈50% had concomitant autoimmune thyroid disease. 61 Notably, patients with PAH have an increased prevalence of both antithyroglobulin and antithyroperoxidase antibodies. 61


The development of hyperthyroidism itself can lead to arrhythmias and worsening right-sided HF and is magnified in PH patients. Thyroid hormone directly affects the heart, and the peripheral and pulmonary vascular systems. Besides increasing myocardial inotropy and heart rate, a low peripheral vascular resistance may be the direct result of thyroid hormone on arteriolar smooth muscle tone, as it enhances the signaling pathway related to PI3K/akt (phosphatidylinositol 3-kinase/protein kinase B) thus increasing 3 nitric oxide synthase isoforms in endothelial and muscular cells. 65 A high cardiac output state in the setting of hyperthyroidism may aggravate PH and exacerbate RV dysfunction, which may result in cardiac decompensation. In addition, hyperthyroidism may also exert direct remodeling or functional effects on the pulmonary vasculature and heart. 65 Possible mechanisms include enhanced catecholamine sensitivity, increased metabolism of intrinsic pulmonary vasodilators, and decreased metabolism of vasoconstrictors. In patients with hyperthyroidism, Grave’s disease antibody levels directly correlated with pulmonary artery pressure.

Metabolic Syndrome and Diabetes Mellitus

The metabolic syndrome is highly associated with PH-LHD. 66 Loss of myocardial compliance because of metabolic derangements of cardiac muscle and increased LV mass lead to increased afterload and resultant postcapillary PH. Patients with PAH and metabolic syndrome associated comorbidities did worse in the REVEAL registry, including reduced exercise capacity (hypertension, diabetes mellitus, obesity), higher functional class (obesity), and higher mortality (diabetes mellitus). 66

Registry data indicate a higher than expected prevalence of diabetes mellitus in PAH patients. 67 Older patients are more likely to have diabetes mellitus, and the combination of diabetes mellitus and PAH is associated with a higher mortality. 67 While epidemiologic data indicate an association, they cannot show that diabetes mellitus itself leads to PAH or accelerates the disease, or vice versa. Research however indicates that the effects of hyperglycemia and insulin resistance on pulmonary microcirculation, and perhaps the RV, may modify the course of PH. 68

Insulin resistance is linked to deficiency of the nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma), which is also reduced in human PAH and is involved in growth and apoptosis regulation of endothelial cells and smooth muscle cells. 69 Accordingly, targeted deletion of PPARγ in smooth muscle cells led to development of PH in animal models, and treatment with PPARγ activators halted the progression of experimental PH, 70 and prevented right HF via fatty acid oxidation. 71 Furthermore, hyperglycemia inhibits endothelial NO synthase and promotes the liberation of reactive oxygen species and activation of protein kinase C, leading to vasoconstriction and inflammation. 68

In addition to its impact on the pulmonary vasculature, the role of diabetes mellitus in RV fibrosis and ischemia also likely influences disease course and prognosis of PAH patients. As in the microcirculation, local hyperglycemia in the RV stimulates the expression of growth factors such as endothelin-1, platelet-derived growth factor and TGF-β, resulting in fibrosis and inflammation. 68 Likewise, insulin resistance in the heart upregulates the diabetic marker microRNA miR-29 family, causing cardiac fibroblasts to increase collagen production and myocardial fibrosis. 72 Although not specifically shown for the RV, the impact of diabetes mellitus on microvessels promoting ischemia in numerous vascular beds is well established. Given the impact of diabetes mellitus on RV fibrosis and the microvasculature, the diabetic milieu in the right heart likely deteriorates the adaptation of the RV to an increased afterload, and thus RV/pulmonary artery coupling in PAH.

Inflammation and Immune System, Coagulation Disorders, and Platelets

Inflammation and Immune System

Inflammation is involved in PAH pathobiology and may occur as a consequence of PAH in the lungs and various other organ systems. There is systemic interaction between lungs, heart, and kidney, where soluble inflammatory mediators and regulators of innate and adaptive immunity are secreted in response to PH-associated RV hypertrophy/dilation and kidney injury, which may act locally or affect distant organs. 28 Consequently, patients with PAH have elevated circulating levels of inflammatory mediators in the blood and lungs, which are predictive for survival. 73 Classic severe PAH lesions contain pulmonary perivascular inflammatory infiltrates composed of T and B lymphocytes, mast cells, dendritic cells, and macrophages. 74 The pulmonary vasculature responds to circulating inflammatory stimuli by increased proliferation or migration and apoptotic-resistant phenotype producing smooth muscle cell hyperplasia, adventitial remodeling, and endothelial dysfunction. 74 Both B cells and T cells contribute to the pro-inflammatory environment. The increased production of interleukin-1 and interleukin-6 promotes activation, proliferation, and differentiation of B lymphocytes. 73 Regulatory T-cells are dysfunctional in various forms of PAH, which occurs in a leptin-dependent manner in idiopathic and connective tissue disease-associated PAH, but irrespective to leptin levels in heritable PAH. 75 Circulating autoantibodies against endothelial cells and smooth muscle cells, which alter different components of the vascular wall in various tissues, have been described in patients with IPAH and scleroderma-associated PAH. 74,76 Whether immune dysregulation may represent the cause or the effect of PAH is not entirely known, but the systemic character of circulating inflammatory mediators and organ interaction should be recognized. 28,74

Coagulation System

Increased plasma concentrations or plasma activities, respectively, of procoagulatory factors such as fibrinogen, von Willebrand factor, and plasminogen-activator inhibitor-1 have been described in patients with PAH and CTEPH. 77 Some patients with high pulmonary shear stress conditions may develop an acquired von Willebrand syndrome. 78 On the other hand, thrombi are commonly detected in the small pulmonary arteries in IPAH. 79 While anticoagulation was previously recommended in all patients with idiopathic, heritable, and anorexigen associated PAH, the overall level of evidence to support this is weak, and current guidelines now recommend that this decision be made on a case by case basis for the above subgroups, and recommend against routine anticoagulation for other PAH subgroups. 80 In contrast, lifelong anticoagulation is strongly recommended for CTEPH.


Thrombocytopenia (ie, platelet count <150 × 10 9 /L) has been reported in up to 20% of patients with idiopathic PAH and seems to be related to disease severity. 81 Thrombocytopenia is also commonly found in patients with portopulmonary hypertension as a result of hypersplenism. The mechanisms causing thrombocytopenia in IPAH are enigmatic. However, the observation that it is almost exclusively found in patients with severe disease may suggest a pulmonary thrombotic microangiopathy in these patients. There is no evidence that other forms of PH are also associated with thrombocytopenia, except for some hematological conditions and PAH patients with Eisenmenger syndrome who have a higher platelet size, mean platelet volume, thrombocytopenia, and platelet dysfunction, all of which may contribute to the higher risk of thrombosis and bleeding seen in these patients. 82 Chronic platelet activation as evidenced by higher plasma P-selectin, β-thrombo-globulin, and platelet factor-4 may play a role in Eisenmenger patients with erythrocytosis. 83

Cognitive Function, Depression, and Anxiety

As is the case in many chronic disorders, anxiety and depression are common in PH and are associated with disease severity 84 however, impairment of cognitive function has also been noted in PH. 85 One study of 46 patients with PAH demonstrated cognitive sequelae in 58% of patients. Moderate-to-severe depression and anxiety were also present in 26% and 19% of patients, respectively. 86 A lower quality of life was not seen in patients with worse cognitive function, although quality of life was associated with working memory. There were no clear differences in disease severity between those with and without cognitive impairment.

It has been suggested that cognitive impairment may relate to impaired cerebral tissue oxygenation. In an interventional study examining the impact of PAH therapies on cognitive function, baseline cerebral tissue oxygenation as measured by near-infrared spectroscopy and 6-minute walk distance were the two independent predictors of cognitive function and cerebral tissue oxygenation on multiple regression analysis. 86 After the introduction of PAH therapies there was a significant improvement in cognitive function on an array of tests, but no change in cerebral tissue oxygenation, and indeed there was no correlation between change in cerebral tissue oxygenation and improvement in cognitive function.

Pulmonary endarterectomy in CTEPH patients involves deep hypothermic circulatory arrest and there have been concerns that this may result in cognitive impairment. A randomized trial was conducted to compare deep hypothermic circulatory arrest with antegrade cerebral perfusion, which showed no difference between the two techniques in terms of impact on cognitive function. 87 Rather, there was an improvement in both groups by 12 weeks after surgery, possibly linking cardiovascular with cognitive function.

Ocular involvement in patients with PH has not been systematically studied. Several case reports have described open-angle glaucoma, retinal detachment, venous stasis retinopathy, ciliary detachment, and central retinal vein occlusion in patients with PAH, most of whom presented with elevated right-sided cardiac filling pressures. 88,89 It is conceivable that not PH itself, but systemic venous congestion affects the eyes, in particular by causing choroidal and retinal venous stasis. However, the frequency and clinical relevance of such findings are unknown.

Autonomic Function and Peripheral Endothelial Function

While PAH is primarily recognized as a pulmonary vascular disease imposing hemodynamic stress on the RV, the course of the disease may be subject to variation by circulating neurohormonal mediators (eg, sympathetic nervous system, renin-angiotensin-aldosterone system) and autonomic dysfunction which may act as disease modifiers. 90 In PAH, as well as in other forms of PH, there is compelling evidence for both sympathetic and parasympathetic abnormalities that are not restricted to advanced stages of RV failure but also occur in early stages. For instance, elevated circulating levels of norepinephrine are found in IPAH and associated forms of PAH, which act systemically and represent an independent predictor of clinical deterioration. 90

Altered autonomic function in PH thus has several important consequences: (1) Adrenoceptor (α1, β1, D1-5) downregulation and desensitization, caused by adrenergic overspill and mediated through GRK2 (G-protein-coupled receptor kinase-2), represent hallmarks of maladaptive RV remodeling and may explain the poor long-term response of the failing RV to inotropes 90 (2) Impairment of autonomous control reduces heart rate variability in right HF, which correlates with pulmonary artery pressure in patients with IPAH and has prognostic significance in various cardiac diseases 91 (3) Lower adrenergic baroreflex sensitivity in PAH patients is associated with a greater susceptibility to systemic (orthostatic) hypotension, cerebral hypoperfusion, and syncope, which is also indicative of poor outcome 92 (4) It was recently shown in animal models that sympathetic overactivity and electrophysiological cellular remodeling in experimental PH were linked to an increased vulnerability to atrial fibrillation and atrial flutter, 93 which are associated with poor outcome in human PAH 94 (5) There is also a link between immune dysregulation, autonomic dysfunction, and endothelial dysfunction in PAH. 74 Several studies have shown that patients with PAH display impaired peripheral endothelial function as assessed by measurement of brachial artery flow-mediated dilation or the peripheral arterial tone ratio. 95

Although several recent studies have investigated a potential role of pharmacological (β-adrenoceptor blockade [95]) or interventional approaches (pulmonary artery denervation, renal denervation) 96 to modify autonomic function in PAH, such approaches may be detrimental and are yet to be properly assessed.

Sleep and Hypoxemia

Patients with PH frequently report poor sleep quality which associates with worse functional status, exercise capacity, quality of life, and psychological disorders. 97,98 Sleep-disordered breathing is common in patients with various forms of PH. Wide variations in the rates of central and obstructive sleep apnea have been reported, 97,98 with rates of obstructive sleep apnea varying from 10% to 50%. Furthermore, because of the underlying gas exchange disturbances in PH, hypoxemia may occur or worsen at night, and daytime measurements may underestimate nocturnal oxygen desaturations. 99 In a cohort of 46 patients with PAH and CTEPH, nocturnal hypoxemia was observed in 83% of patients, with the major mechanisms being ventilation-perfusion mismatch in 76%, obstructive sleep apnea in 66%, and overlap in 45%. 97 The degree of nocturnal hypoxemia correlated with worse daytime PaO2 and distal airways narrowing (FEV25-75). No significant differences were found between patients desaturating and those not desaturating in terms of PH severity, however, numbers were small, and multivariate logistic regression showed that a higher pulmonary artery pressure and lower FEV25-75 predicted overnight hypoxemia.

There are insufficient data to evaluate whether sleep-disordered breathing or nocturnal hypoxemia adversely affects long-term outcomes. However, nocturnal oxygen therapy over 1 week improved 6-minute walking distance, nocturnal heart rate, and corrected QT interval in patients with precapillary PH and isolated nocturnal hypoxemia or >10 oxygen dips per hour. 100

Treatable Traits: Towards Precision Medicine in PH

Recognizing PH as a disease with various systemic implications leads to the identification of treatable traits in individual patients and to a personalized treatment approach. Assessments and interventions most strongly recommended in current PH guidelines include routine measurement of renal function, anemia, and thyroid function, and periodic assessment of oxygen saturation during both the day and night. Treatment should include correction of hypoxemia if present, use of diuretics in patients with fluid retention from right heart failure, and supervised exercise training in patients with deconditioning. 80 Other interventions may be considered on a case by case basis, as shown in Figure 5.

Figure 5. Treatable traits in pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). Frequent consequences and factors contributing to disease progression and clinical deterioration. In addition to targeted therapies, the disease course may be influenced by pharmacological/interventional approaches or supportive care.


Although a large body of evidence indicates that systemic consequences of PH and right-sided HF place additional burden on patients and contribute to adverse outcome, this is often underestimated. Regardless of the underlying cause of PH, the common final path is right-sided HF. As a consequence, both systemic venous congestion caused by RV dysfunction and impaired peripheral perfusion caused by right-left heart interaction and diminished systemic output contribute to insult to multiple organ systems and interorgan crosstalk, which may result in a systemic inflammatory state that needs to be further characterized. It should be pointed out that many of the available evidence on secondary organ damage (particularly on liver and kidney impairment) is primarily related to left HF, whereas the consequences of isolated right-sided HF caused by PAH or other forms of precapillary PH are far less well studied and require further research (Table). However, when summarizing the available evidence, it becomes clear that even in patients with LHD, right-sided rather than left-sided HF is the main driver of secondary organ dysfunction. The important role of the right heart in this context is frequently underestimated in clinical practice and needs to be further studied. This knowledge is key to the understanding and treating of secondary organ dysfunction in patients with left heart disease as well as other forms of PH leading to right-sided HF.

Table. Consequences of Right-Sided HF and PH in Various Organ Systems

CLD indicates chronic lung disease COPD, chronic obstructive pulmonary disease CTEPH, chronic thromboembolic pulmonary hypertension DM, diabetes mellitus HF, heart failure HFpEF, heart failure with preserved ejection fraction HFrEF, heart failure with reduced ejection fraction HPAH, heritable PAH IPAH, idiopathic PAH LA, left arterial LHD, left heart disease LV, left ventricle MS, metabolic syndrome PA, pulmonary artery PAH, pulmonary arterial hypertension P(A)H, PH or PAH PAI-1, plasminogen activator inhibitor-1 PH, pulmonary hypertension RA, right arterial RV, right ventricle and vWF, von Willebrand factor.

Sources of Funding

This work was supported in part by the Deutsche Forschungsgemeinschaft (GRK-2407 to Dr Rosenkranz).


Dr Rosenkranz has received remunerations for lectures or consultancy from Abbot, Actelion, Arena, Bayer, Gilead, GSK, Merck, Novartis, Pfizer, and United Therapeutics. His institution has received research grants from Actelion, Bayer, Novartis, Pfizer, and United Therapeutics. Dr Howard has received fees for lectures or consultancy from Actelion, Bayer, GSK, and Merck. His institution has received research grants from Bayer. Dr Gomberg-Maitland served as a consultant and as a member of steering committees and DSMB/event committees for Actelion, Bayer, Gilead, Medtronic, UCB, Bellerophon (formerly known as Ikaria), and United Therapeutics. She has received honoraria for CME from Medscape and ABComm. Actelion, Bayer, Gilead, Medtronic, Lung Biotechnology, and Reata have provided funding to the University of Chicago during the last year to support her conduct of clinical trials. She is a member of the PCORI Advisory Panel on Rare Diseases and a Special Government Employee for the FDA Cardio-Renal division. Dr Hoeper has received fees for lectures or consultancy from Actelion, Bayer, Gilead, GSK, Merck, and Pfizer.


Sources of Funding, see page 690

What is the difference between the pulmonary and bronchial circulation?

The pulmonary arteries carry deoxygenated blood at low pressure. They supply 99% of the blood flow to the lungs and participate in gas exchange at the alveolar capillary membrane. The bronchial arteries carry oxygenated blood to the lungs at a pressure six times that of the pulmonary arteries.

Secondly, what is Perfusing of the lungs? Bronchial artery. In human anatomy, the bronchial arteries supply the lungs with nutrition and oxygenated blood. Although there is much variation, there are usually two bronchial arteries that run to the left lung, and one to the right lung.

Also, what is pulmonary circulation and what is its function?

The pulmonary circulation is the portion of the circulatory system which carries deoxygenated blood away from the right ventricle, to the lungs, and returns oxygenated blood to the left atrium and ventricle of the heart.

What veins and arteries supply the lungs?

The blood supply to the tissues of the lung, its lymph nodes, bronchi and visceral pleura, comes from the bronchial arteries. The venous drainage of the alveoli and the small bronchi is provided by the pulmonary veins, whereas that of the larger bronchi is via the bronchial veins.

Pregnancy is not recommended in women with PH. The changes associated with pregnancy and delivery produce changes that can seriously endanger the life of the mother and baby. Therefore it is important for women with PH to use a more permanent but safe form of contraception. Because estrogen can aggravate PH, it's important to avoid any contraception containing estrogen. Progesterone forms of contraception are preferable. It is generally recommended that women with PH have tubal ligation or use the Mirena IUD. See the section on Birth Control and Pregnancy for more information.

Additional precautions are often taken with PAH patients. These include supplemental oxygen during air travel, antibiotic therapy for significant respiratory tract infections, pneumococcal pneumonia vaccine and yearly flu vaccines (since pneumonia can be very serious with PH patients). Also avoid conditions in which the ambient oxygen concentration may be decreased, such as high altitude and travel in unpressurized airplane cabins. Before starting an exercise program, ask your physician what activities are appropriate for you. Finally, if you've begun medical treatment for your PAH, stopping any of your medicines without your physician's approval can be extremely dangerous. Medical therapy has significantly improved the outlook for most patients with pulmonary hypertension, but it doesn't "cure" it. Don't stop medical therapies unless your physician (trained in caring for PAH patients) recommends doing so.

Risk Factors - Pulmonary Hypertension

You may have an increased risk for pulmonary hypertension because of your age, environment, family history and genetics , lifestyle habits, medicines you are taking, other medical conditions, or sex.

Your risk of pulmonary hypertension goes up as you get older, although it may occur at any age. The condition is typically diagnosed between ages 30 and 60.

You may be at an increased risk of pulmonary hypertension if you have or are exposed to the following:

  • Asbestos or silica
  • Infection caused by parasites such as schistosomiasis or Echinococcus, which are tapeworms

Certain genetic disorders, such as Down syndrome, congenital heart disease, and Gaucher disease, can increase your risk of developing pulmonary hypertension.

A family history of blood clots or pulmonary embolism also increases your risk of developing pulmonary hypertension.

Unhealthy lifestyle habits can increase the risk of pulmonary hypertension. These habits include:

  • Illegal drugs, such as cocaine and amphetamines
  • Smoking

Some medicines may increase your risk of pulmonary hypertension, including:

  • Chemotherapy medicines to treat cancer , such as dasatinib, mitomycin C, and cyclophosphamide
  • Selective serotonin reuptake inhibitors (SSRIs) to treat depression and anxiety. SSRIs may cause pulmonary arterial hypertension in newborns whose mothers have taken these medicines during pregnancy.
  • Weight-loss drugs such as fenfluramine and dexfenfluramine, which are no longer approved for weight loss in the United States

Certain medical conditions may increase your risk of developing pulmonary hypertension:

  • Blood clotting disorders, such as blood clots in the lungs, a higher-than-normal platelet count in your blood, and conditions that make your blood more likely to clot, such as protein S and C deficiency, factor V Leiden thrombophilia, antithrombin III deficiency, and antiphospholipid syndrome
  • Chronic kidney disease
  • Diseases that change the structure of the chest wall, such as scoliosis
  • Infections such as hepatitis B or C
  • Liver disease such as cirrhosis
  • Surgical removal of the spleen
  • Thyroid diseases

Pulmonary hypertension is more common in women than in men. Pulmonary hypertension with certain types of heart failure is also more common in women.


Dalton’s law: statement of the principle that a specific gas type in a mixture exerts its own pressure, as if that specific gas type was not part of a mixture of gases

external respiration: gas exchange that occurs in the alveoli

Henry’s law: statement of the principle that the concentration of gas in a liquid is directly proportional to the solubility and partial pressure of that gas

internal respiration: gas exchange that occurs at the level of body tissues

partial pressure: force exerted by each gas in a mixture of gases

total pressure: sum of all the partial pressures of a gaseous mixture

ventilation: movement of air into and out of the lungs consists of inspiration and expiration