In medicine, pulmonary hypertension (PH) or pulmonary artery hypertension (PAH) is an increase in blood pressure in the pulmonary artery or lung vasculature. Depending on the cause, it can be a severe disease with a markedly decreased exercise tolerance and right-sided heart failure. Medicine is a branch of health science concerned with maintaining health and restoring it by treating disease. ... The pulmonary arteries carry blood from the heart to the lungs. ... The heart in relation to the lungs (from an older edition of Grays Anatomy) This x-ray of the human chest shows the lungs as dark regions The lung is an organ belonging to the respiratory system and interfacing to the circulatory system of air-breathing vertebrates. ...

Signs and symptoms

A history usually reveals gradual onset of shortness of breath, fatigue, angina pectoris, syncope (fainting) and peripheral edema. Dyspnea (Latin dyspnoea, Greek dyspnoia from dyspnoos - short of breath) or shortness of breath (SOB) is perceived difficulty breathing or pain on breathing. ... Syncope can also mean fainting (in medicine). ... Edema (BE: oedema, formerly known as dropsy) is swelling of any organ or tissue due to accumulation of excess fluid. ...

In order to establish the cause, the physician will generally conduct a thorough medical history and physical examination. A detailed family history is taken to determine whether the disease might be familial. In medicine, physical examination is the process by which the physician investigates the body of a patient for signs of disease to aid in determining the correct diagnosis. ...

Diagnosis

Normal pulmonary arterial pressure in a person living at sea level has a mean value of 12-16mmHg. Definite pulmonary hypertension is present when mean pressures at rest exceed 25 mmHg. Although pulmonary arterial pressure can be estimated on the basis of echocardiography, pressure sampling with a Swan-Ganz catheter provides the most definite measurement. The echocardiogram is an ultrasound of the heart. ...

Diagnostic tests generally involve blood tests, electrocardiography, arterial blood gas measurements, X-rays of the chest (generally followed by high-resolution CT scanning). A biopsy of lung tissue, angiography with endoluminal biopsy of the pulmonary artery, or biopsy of any associated skin lesions, is often attempted to obtain tissue for histopathological investigation. Blood tests are laboratory tests done on blood to gain an appreciation of disease states and the function of organs. ... ECG may also refer to the East Coast Greenway Lead II An Electrocardiogram (ECG or EKG, abbreviated from the German Elektrokardiogramm) is a graphic produced by an electrocardiograph, which records the electrical voltage in the heart in the form of a continuous strip graph. ... Arterial blood gas measurement is a blood test is performed to determine the concentration of oxygen, carbon dioxide and bicarbonate, as well as the pH, in the blood. ... In the NATO phonetic alphabet, X-ray represents the letter X. An X-ray picture (radiograph) taken by Röntgen An X-ray is a form of electromagnetic radiation with a wavelength approximately in the range of 5 pm to 10 nanometers (corresponding to frequencies in the range 30 PHz... CAT apparatus in a hospital Computed axial tomography (CAT), computer-assisted tomography, computed tomography, CT, or body section roentgenography is the process of using digital processing to generate a three-dimensional image of the internals of an object from a large series of two-dimensional X-ray images taken around... A biopsy (in Greek: bios = life and opsy = look/appearance) is a medical test involving the removal of cells or tissues for examination. ... Angiography or arteriography is a medical imaging technique in which an X-ray picture is taken to visualize the inner opening of blood filled structures, including arteries, veins and the heart chambers. ... The pulmonary arteries carry blood from the heart to the lungs. ... A biopsy (in Greek: bios = life and opsy = look/appearance) is a medical test involving the removal of cells or tissues for examination. ... Anatomic pathology is the branch of pathology that is concerned with the diagnosis of disease based on the gross and microscopic examination of cells and tissues. ...

Clinical improvement is often measured in a "six-minute walking test", i.e. the distance a patient can walk in six minutes.

Causes and mechanisms

Pulmonary hypertension can be primary (occurring without an obvious cause) or secondary (a result of other disease processes.)

Primary PH

Primary pulmonary hypertension (PPH) is considered a genetic disorder. It has been linked to mutations in the BMPR2 gene, which encodes a receptor for bone morphogenic proteins (Deng et al, 2000), as well as the 5-HT(2B) gene, which codes for a serotonin receptor (Blanpain et al, 2003). Recently, characteristic proteins of human herpesvirus 8 (also known for causing Kaposi sarcoma) were identified in vascular lesions of PPH patients (Cool et al, 2003). However, it is not understood what roles these genes and viral particles play in PPH. PPH has also been associated to the use of appetite suppressants (e.g. Fen-phen, see Abenhaim et al, 1996). While genetic susceptibility to adverse drug reactions is suspected, the cause of the disease is still largely unknown. A genetic disorder, or genetic disease is a disease caused, at least in part, by the genes of the person with the disease. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm that binds to a specific factor (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... 2000 is a leap year starting on Saturday of the Gregorian calendar. ... Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesised in serotonergic neurons in the central nervous system and enterochromaffin cells in the gastrointestinal tract. ... 2003 is a common year starting on Wednesday of the Gregorian calendar. ... Genera Subfamily Alphaherpesvirinae    Simplexvirus    Varicellovirus    Mardivirus    Iltovirus Subfamily Betaherpesvirinae    Cytomegalovirus    Muromegalovirus    Roseolovirus Subfamily Gammaherpesvirinae    Lymphocryptovirus    Rhadinovirus Unassigned    Ictalurivirus The Herpesviridae are a family of DNA viruses that cause diseases in humans and animals. ... Anorectics, anorexigenics or appetite suppressants, are substances which reduce the desire to eat (anorectic, from the Greek an- = not and oreg- = extend, reach). Used on a short term basis clinically to treat obesity, some appetite suppressants are also available over the counter. ... Fen-phen was an anti-obesity medication (an anorectic) which consisted of two drugs: fenfluramine and phentermine. ... 1996 is a leap year starting on Monday of the Gregorian calendar, and was designated the International Year for the Eradication of Poverty. ...

PPH is very rare but often fatal. Patients usually have no symptoms until they reach their late twenties or early thirties. It is characterized by elevated pulmonary vascular resistance attributable to the abnormal thickening of the vessel wall and narrowing of the lumen of arterioles in the lungs. Vascular resistance is a term used to define the resistance to flow that must be overcome to push blood through the circulatory system. ... In anatomy, the lumen is the cavity or channel within a tube or tubular structure, such as the vascular lumen of a blood vessel, along which blood flows. ... An arteriole is a blood vessel that extends and branches out from an artery and leads to capillaries. ...

Secondary PH

Secondary pulmonary hypertension (SPH) is often due to chronic obstructive pulmonary disease (COPD). Other factors that have been linked to secondary pulmonary hypertension are: Chronic obstructive pulmonary disease (COPD) is an umbrella term for a group of respiratory tract diseases that are characterised by airflow obstruction or limitation. ...

• congenital heart disease featuring left-right shunting
  • Eisenmenger's syndrome is reversal of the shunt due to pulmonary hypertension
• pulmonary embolism
• pulmonary fibrosis
• systemic sclerosis (scleroderma)
• portal hypertension (the "hepatopulmonary syndrome")
• sarcoidosis
• airway restrictive diseases such as asthma, chronic bronchitis,
• AIDS
• sickle-cell anemia (Gladwin et al, 2004)
• hypothyroidism (Curnock et al, 1999)

A common consequence of chronic pulmonary hypertension is cor pulmonale (right sided heart failure) believed to be caused by the increased load on the right ventricle and atrium of the heart. A chest radiograph (X-ray) will often reveal an enlarged right atrium and ventricle, and prominent pulmonary arteries. An ECG will often demonstrate right ventricular hypertrophy or strain. Oedema and fluid retention follow. Congenital heart disease is heart disease in the newborn, and includes congenital heart defects, congenital arrythmias, and cardiomyopathies. ... Eisenmengers syndrome or Eisenmengers reaction is defined as the process in which a left-to-right shunt in the heart causes increased flow through the pulmonary vasculature, causing pulmonary hypertension, which in turn, causes increased pressures in the right side of the heart and reversal of the shunt... Diffuse parenchymal lung disease (DPLD), also known as interstitial lung disease, refers to a group of lung diseases, affecting the alveolar epithelium, pulmonary capillary endothelium, basement membrane, perivascular and perilymphatic tissues. ... In medicine, portal hypertension is hypertension (high blood pressure) in the portal vein and its branches. ... Bronchitis is an inflammation of the bronchi of the lungs, that causes the cilia of the bronchial epithelial cells to stop functioning. ... AIDS (Acquired Immunodeficiency Syndrome or Acquired Immune Deficiency Syndrome, sometimes written Aids) is a human disease characterized by weakening of the bodys immune system and capacity to fight infection and certain cancers. ... Sickle-shaped red blood cells Sickle cell anemia (American English), sickle cell anaemia (British English) or sickle cell disease is a genetic disease in which red blood cells may change shape under certain circumstances. ... 2004 is a leap year starting on Thursday of the Gregorian calendar. ... Hypothyroidism is the disease state caused by insufficient thyroid hormone by the thyroid gland. ... 1999 is a common year starting on Friday of the Common Era, and was designated the International Year of Older Persons by the United Nations. ... Cor pulmonale is a medical term used to describe a failure of the right side of the heart. ... In the heart, a ventricle is a chamber which collects blood from an atrium (another heart chamber) and pumps it out of the heart. ... In anatomy, the atrium (plural: atria) is the blood collection chamber of a heart. ... Radiography is the creation of radiographs, photographs made by exposing a photographic film or other image receptor to X-rays. ... Lead II An electrocardiogram (ECG or EKG, abbreviated from the German Elektrokardiogramm) is a graphic produced by an electrocardiograph, which records the electrical voltage in the heart in the form of a continuous strip graph. ... Hypertrophy is the increase of the size of an organ. ... Edema (BE: oedema, formerly known as dropsy) is swelling of any organ or tissue due to accumulation of excess fluid. ...

Classification

In 2003, the 3rd World Symposium on Pulmonary Hypertension was convened in Venice to modify classification based on the new understanding of disease mechanisms. The revised system developed by this group provides the current frame work for understanding pulmonary hypertension.

The system includes several improvements over the former 1998 Evian Classification system. The terms "primary" and "secondary" were discontinued because they had limited diagnostic value. In addition, new classifications were added, including primary veno-occclusive disease(PVOD). Risk factor descriptions were updated, and the classification of congenital systemic-to pulmonary shunts was revised. A new classification of genetic factors in PH was recommended, but not implemented because available data were judged to be inadequate.

The Venice 2003 Revised Classification system can be summarized as follows:

• WHO Group I - Pulmonary arterial hypertension(PAH)
• WHO Group II - Pulmonary hypertension with left heart disease
• WHO Group III - Pulmonary hypertension associated with lung diseases and/or hypoxemia
• WHO Group IV - Pulmonary hypertension due to chronic throbotic and/or embolic disease
• WHO Group V - Miscellaneous

These terms are currently in use, but they are not yet as commonly used as the old terms of PPH and SPH.

Epidemiology

Women are almost twice as likely to present with PPH than men.

Treatment

Treatment is determined by the condition underlying the cause of the hypertension. For instance, long term oxygen therapy has been proven to be useful in patients with chronic obstructive pulmonary disease, and when the pulmonary hypertension is due to chronic thromboembolism, inferior vena caval filter insertion or pulmonary endarterectomy can be performed. Chronic obstructive pulmonary disease (COPD) is an umbrella term for a group of respiratory tract diseases that are characterised by airflow obstruction or limitation. ... This article may be too technical for most readers to understand. ...

In PPH, lifestyle changes, digoxin, diuretics, oral anticoagulants, oxygen therapy and vasodilators are the mainstays of treatment. Synthetic prostacyclin (an eicosanoid) per continuous infusion is tried occasionally in some types of pulmonary hypertension. Prostacyclin is available in three forms: by catheter (Flolan), subcutaneously (Remodulin), and recently approved is an inhaled version that is called Ventavis[1] (http://www.4ventavis.com). Digoxin is a cardiac glycoside extracted from the foxglove plant, digitalis. ... A diuretic is any drug that tends to increase the flow of urine from the body (diuresis). ... An anticoagulant is a substance that prevents coagulation; that is, it stops blood from clotting. ... A vasodilator is a substance that causes blood vessels in the body to become wider by relaxing the smooth muscle in the vessel wall. ... Prostacyclin is a member of the family of lipid molecules known as eicosanoids. ... In biochemistry, eicosanoids are a class of oxygenated hydrophobic hormones that largely function as paracrine mediators. ...

A recent addition is bosentan (marketed as Tracleer®), an endothelin receptor antagonist. Two new oral medications are in the final stages of approval: thelin and ambriesatan.

Pulmonary thromboendarterectomy (PTE) is a surgical procedure that is used when pharmaceutical management fails. It is the surgical removal of thrombus (clot) and the lining of the pulmonary artery; it is a large and difficult procedure which is currently performed in San Diego, California. Case series show remarkable success in selected patients. A thrombus is the final product of blood coagulation, through the aggregation of platelets and the activation of the humoral coagulation system. ... City nickname Americas Finest City City flower Carnation City urban tree Jacaranda City native tree Torrey Pine Mayor Dick Murphy* City Attorney Michael Aguirre City Council District One District Two District Three District Four District Five District Six District Seven District Eight Scott Peters Michael Zucchet Toni Atkins Tony...

Prognosis

Several studies have reported a mean survival of 2-3 years from time of diagnosis with the cause of death usually being right ventricular failure (cor pulmonale). Cor pulmonale is a medical term used to describe a failure of the right side of the heart. ...

References

1. Abenhaim L, Moride Y, Brenot F et al. Appetite-Suppressant Drugs and the Risk of Primary Pulmonary Hypertension. N Engl J Med 1996;335:609-16. Abstract (http://content.nejm.org/cgi/content/abstract/335/9/609).
2. Blanpain C, Le Poul E, Parma J, Knoop C, Detheux M, Parmentier M, Vassart G, Abramowicz MJ. Serotonin 5-HT(2B) receptor loss of function mutation in a patient with fenfluramine-associated primary pulmonary hypertension. Cardiovasc Res., 2003;60(3):518-28. Abstract (http://dx.doi.org/10.1016/j.cardiores.2003.09.015)
3. Cool CD, Rai PR, Yeager ME, Hernandez-Saavedra D, Serls AE, Bull TM, Geraci MW, Brown KK, Routes JM, Tuder RM, Voelkel NF. Expression of Human Herpesvirus 8 in Primary Pulmonary Hypertension. N Engl J Med 2003;349:1113-22.
4. Curnock AL, Dweik RA, Higgins BH, Saadi HF, Arroliga AC. High prevalence of hypothyroidism in patients with primary pulmonary hypertension. Am J Med Sci. 1999;318:289-292.
5. Deng Z, Morse JH, Slager SL, et al. Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am J Hum Genet 2000;67:737-44.
6. Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K, Brown B, Coles WA, Nichols JS, Ernst I, Hunter LA, Blackwelder WC, Schechter AN, Rodgers GP, Castro O, Ognibene FP. Pulmonary Hypertension as a Risk Factor for Death in Patients with Sickle Cell Disease. N Engl J Med 2004;350:886-95.

The New England Journal of Medicine (NEJM) is a peer-reviewed medical journal published by the Massachusetts Medical Society. ...

External links

• The Merck Manual of Diagnosis and Therapy: Cor Pulmonale (http://www.merck.com/mrkshared/mmanual/section16/chapter203/203c.jsp)
• The Pulmonary Hypertension Association (http://www.phassociation.org/)
  • Consensus Statements (http://www.phassociation.org/Learn/Consensus-Statements/index.asp)
  • What is Pulmonary hypertension? (http://www.phassociation.org/Learn/What-is-PH/)
• Facts About Primary Pulmonary Hypertension (http://www.nhlbi.nih.gov/health/public/lung/other/pph_doc.htm) from the National Heart, Lung, and Blood Institute (NHLBI)
• Pulmonary Hypertension (http://www.hopkins-lungs.org/programs/ph/) from the Division of Pulmonary and Critical Care Medicine of the Johns Hopkins School of Medicine (http://www.hopkins-lungs.org/).
• Diet Drugs Claim Center - Fen Phen, Redux & Pondimin Claims (http://www.diet-drugs.cc)
• Primary Pulmonary Hypertension (http://www.pph-treatment.org)