In 1884, Flückiger was the first to report the association between liver dysfunction and the development of hypoxemia.  The term<unk> " was first suggested by Kennedy and Knudson almost 100 years later,in 1977 during describing a patient with the classic findings of<unk> .<unk>  can be classified in term of severity based on arterial blood gas analysis.The exact pathogenesis of<unk>  is not fully understood. Pulmonary microvascular dilation and angiogenesis are two central pathogenic features that drive abnormal pulmonary gas exchange in experimental<unk> , and thus might underlie<unk>  in humans. It is thought that<unk>  is the result of microscopic intrapulmonary arteriovenous dilatations due to either increased liver production or decreased the liver clearance of vasodilators, possibly involving nitric oxide. The progression to<unk>  is believed that involves the nitric oxide metabolism. The dilation of these blood vessels causes overperfusion relative to ventilation, leading to ventilation-perfusion mismatch and hypoxemia. Patients with<unk>  have platypnea-orthodeoxia<unk>  (POS); that is, because intrapulmonary vascular dilations (IPVDs) predominate in the bases of the lungs, standing worsens hypoxemia (orthodeoxia)/dyspnea (platypnea) and the supine position improves oxygenation as blood is redistributed from the bases to the apices. Additionally, late in cirrhosis, it is common to develop high output failure, which would lead to less time in capillaries per red blood cell, exacerbating the hypoxemia. Mild hypoxemia occurs in 30 percent of patients with chronic liver disease. It may be due to common cardiopulmonary diseases such as congestive heart failure, chronic obstructive pulmonary disease (COPD) or pneumonia. Pulmonary vascular bed malfunction also might be responsible for certain conditions such as<unk>  <unk>  and portopulmonary hypertension (PPH).<unk>  <unk>  must be differentiated from portopulmonary hypertension (PPH) and hereditary hemorrhagic telangiectasia (HHT). Neither specific etiology nor severity of cirrhosis have been found to be correlated with the incidence or severity of<unk> .<unk>  occurs in both males and females, in children and adults, and in people of all ethnic backgrounds. Even patients with non-cirrhotic portal hypertension with normal synthetic liver function (e.g. nodular regenerative hyperplasia) may develop<unk> , nonetheless, cirrhosis remains the most common cause of<unk> . There are no established risk factors for<unk> . Literally, It can happen in almost every patient with liver disease regardless of their disease stage, severity, chronicity, age, sex, or race. Nevertheless, polymorphism in nitric oxide and angiogenesis genes has been observed in patients who develop<unk> . There is insufficient evidence to recommend routine screening for<unk> . Nevertheless, it should be considered as a differential diagnosis in every patient with known liver disease or sign and symptoms of liver disease that present with hypoxemia, and dyspnea. Nevertheless, serial pulse oximetry as a simple, low cost and widely available technique, is recommended in cirrhotic patients. It could detect and also determine the severity of hypoxemia in patients with<unk> . Hence, pulse oximetry screening might improve management of<unk>  in cirrhotic patients. If left untreated, prognosis is generally poor, and the 2.5 year mortalityl rate of patients with<unk>  is approximately 40% to 60%. With liver transplantation, the 5 year survival rate is 74%, which is comparable to patients who undergo liver transplants who do not suffer from<unk> . There is no single diagnostic study of choice for the diagnosis of<unk> , but<unk>  can be diagnosed based on history of liver disease, atrial blood gas analysis (widened alveolar-arterial oxygen gradient measurement); and evidences of intra-pulmonary vascular dilation or arterio-venous communications that result in a right-to-left intrapulmonary shunt.
Physical examination of patients with<unk>  is usually remarkable for liver disease findings such as jaundice, palmar erythema, spider angiomata, gynaecomastia ,abdominal distension, caput medusae, splenomegaly either with or without sign and symptoms of hypoxemia such as cyanosis and clubbing.The presence of platypnea on physical examination is highly suggestive of<unk> . Atrial blood gas analysis (ABG) is used both for diagnosis and evaluating the severity (grade) of<unk> .
Both contrast-enhanced transthoracic and transesophageal echocardiography may be helpful in the diagnosis of<unk> . In fact, contrast-enhanced transthoracic echocardiography with agitated saline is the most practical method to detect pulmonary vascular dilation. It can not only diagnose the presence of shunt but also can distinguish between intracardiac and intrapulmonary shunt. Findings on an echocardiography suggestive of<unk>  include the presence of agitated saline bubbles after injection in a peripheral vein in the patient’s arm. The timing of the appearance of the left-sided bubbles after injection can determine the source of the shunt. while bubbles appear in the left chambers three cardiac cycles after the appearance of the bubbles in the right heart chambers in intracardiac shunting, in intrapulmonary shunting, four to six cardiac cycles are passed before appearance of the bubbles in the right heart chambers. Transesophageal echocardiography (TTE) is also helpful in the diagnosis of<unk> . TTE can detect intrapulmonary vascular dilations with greater specificity compared to transthoracic echocardiography since the examiner can directly observe microbubbles in the pulmonary veins as they enter the left atrium. Additionally, cardiac function and pulmonary artery pressures can also be evaluated. Technetium 99m-labeled macroaggregated albumin scanning also may be helpful in the diagnosis of<unk> . labeled albumin macroaggregates (>20 microns in diameter) are injecting intravenously. Macroaggregates exceed the normal pulmonary capillary diameter and should be trapped normally. Scans that identify uptake of the radionucleotide by the brain suggest that the macroaggregates passed through either an intrapulmonary or intracardiac shunt. A calculated shunt fraction of above 6% is abnormal. Nevertheless, it can not distinguish between intracardiac and intrapulmonary shunting and has a lower sensitivity compared to contrast-enhanced echocardiography. Pulmonary function tests may be helpful in the diagnosis of<unk> . Findings suggestive of<unk>  include A decrease in the single-breath diffusing capacity for carbon monoxide (DLCO) suggesting a diffusion impairment as a frequent finding in<unk>  (occurring in up to 80% of patients). Six minute walk test with and without an oxygen titration can also use as an objective assessment of exercise capacity. There is no medical treatment for<unk> . The mainstay of treatment for<unk>  is surgery. Orthotopic liver transplantation is the only available treatment for patients with<unk> . Supportive therapy for<unk>  includes oxygen therapy. Effective measures for the secondary prevention of<unk>  include considering the diagnosis in every patient with liver disease which present with hypoxemia and shortness of breath, looking for diffusion defects in arterial blood gas analysis, and considering specific examinations such as agitated saline contrast echocardiography in selected patients.
Hepatopulmonary syndrome
Multiple organ dysfunction syndrome
Hepatic encephalopathy
Hepatorenal syndrome
Nephritic syndrome
Waterhouse–Friderichsen syndrome
Decompression sickness
Sepsis