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Pulmonary hypertension (IP) is a pathological condition characterized by an increase in blood pressure within the pulmonary artery, the vessel carrying the blood volume from the right heart to the lungs. The normal pressure in the pulmonary artery has an average value between 12 and 16 mmHg; Let's talk about pulmonary hypertension when this value is > 25 mmHg at rest. A classification has been created that aims to group the various forms of IP according to the common mechanism that has led to the development of the disease and consequently to the same therapeutic path that can be undertaken. This allows to describe in a clearer way the alterations that characterize the disease and above all to assign a correct therapy according to the group of the classification. All therapies that are described in this manual have been approved for some forms of pulmonary hypertension but not for others.
Diagnostic classification of pulmonary hypertension (Dana Point, 2008):

1. Pulmonary arterial hypertension

  • Idiopathic
  • Hereditary (BMPRII, ALK1, others)
  • Drugs and Toxins
  • Associated with: Connective diseases HIV infection Hypertension portal Congenital heart disease schistosomiasis hemolytic anemia Chronic
  • Persistent hypertension of the newborn

1. IAP with Venulare/capillary impairment

2. Secondary IP to left heart diseases

  • Left ventricular systolic or diastolic dysfunction
  • Valve

3. IP secondary to respiratory diseases and/or hypoxemia

  • Chronic obstructive obstructive (COPD)
  • Interstitial
  • Night Apnea
  • IP from altitude
  • Developmental alterations

4. Secondary IP to chronic thromboembolism

  • Operable
  • Not operable

5. Miscellany
Myeloproliferative disorders, sarcoidosis, neurofibromatosis, histiocytosis X, lymphangioleiomyomatosis, vasculitis etc.


I Group: Pulmonary Arterial hypertension (IAP)
All the forms of IAP belonging to the first group of the classification are united by the same alterations on the cells that coat the pulmonary vessels. These alterations involve obstruction of the small arteries, secondary to the proliferation of the cells that coat the vessel and the formation of small trumpets. This causes a major obstacle to blood flow and a consequent increase in pulmonary pressure. The female sex is more affected; The age with higher prevalence of disease is between the third and fourth decade of life, but children or elderly people are not spared. In the other groups of the classification the IP is a consequence of other illnesses.
Idiopathic IAP
The idiopathic IAP is a rare disease and is the most severe form of pulmonary arterial hypertension. In this type of IAP the causes that lead to typical changes in the blood vessels of the lung are not known, it is therefore called "idiopathic" (formerly known as the "primitive").
Hereditary IAP
The IAP is a complex disease caused by many factors, in which a genetic predisposition may exist that confers a particular response of the lung vessels to stimuli of various kinds. The IAP is hereditary in 7-10% of cases. It is believed that various genes may be involved in the development of the disease, some of which have been identified as producing cell receptors involved in cell destruction and multiplication. One of the genes involved in the familial IAP was located on the long arm of chromosome 2, specifically 2q31-32. The gene is autosomal dominant with incomplete penetrance (autosomal means that it is not on the X or Y chromosome that determines sex; dominant means that a parent is enough to transmit it; With incomplete penetrance we mean that even if you own that gene you can not Develop the IAP). The disease present in a family can sometimes jump generations, but in the next offspring tends to be more severe and to manifest in increasingly early age (genetic advance). Women with the gene seem more prone to developing the disease than men are. A predisposition to the development of the IAP may also result from sporadic genetic alterations.
Drugs and Toxins
In patients who have taken anorectics drugs, which act by causing a loss of appetite, (Aminorex, Fenfluramine, Dexfenflura-Mina) The prevalence of the disease is rather low (1 case every 10,000-17,000 subjects) but may vary according to the duration of exposure to the toxic substance. If the disease is caused by the intake of these drugs, the IP is part of the group of pulmonary arterial hypertension. A sudden rise in Europe of the IAP between the years 1967 and 1973 was linked to the spreading of these pills. The increase of this pathology in the United States in the 1990s, led the pharmaceutical industries that produced these tablets to withdraw them from the market (September 1997). Therefore, if in the course of life you have taken medications to lose weight, it is recommended to carry out a medical check. Sometimes the IAP related to the intake of fenfluramine or Dexenfluramina appears after a period of latency from the cessation of therapy; In many people it may not be noticeable until two years later. Drugs such as cocaine and methamphetamine can in rare cases cause IAP, with a mechanism not yet clear. The intake of contaminated food oil, L-tryptophan and the ingestion of Crotalaria are also associated with the IAP.
IAP associated with connective tissue diseases
The prevalence of pulmonary arterial hypertension in connective diseases is much higher than in other diseases. Scleroderma is the main connective disease associated with pulmonary arterial hypertension, but also rheumatoid arthritis, systemic lupus erythematosus (SLE), CREST syndrome, vasculitis, mixed connectivity and sarcoidosis, can lead To the IP, both through the involvement of the blood vessels that progressively become obstructed, and determining a pulmonary fibrosis.
IAP associated with HIV infection
HIV infection can be associated, in rare cases, with the IAP through little-known mechanisms. The IAP can be presented at any stage of the disease and the changes to which the blood vessels of the lung are encountered are very similar to those observed in the idiopathic IAP.
IAP associated with portal hypertension
Hepatic cirrhosis, in rare cases, may be associated with pulmonary arterial hypertension through poorly known mechanisms, but in part linked to the high blood flow through the lung.
IAP associated with congenital heart disease
The presence of congenital defects at the level of the various structures that form the heart can cause IAP. These imperfections allow the passage of blood from the left heart, to greater pressure, to the right heart, to lower pressing or less, with a consequent increase in the flow of blood in the lungs. In the long run this mecccanismo can lead to Eisenmenger syndrome: the pulmonary arteries subjected to a constant increase of blood flow and pressure undergo irreversible anatomical alterations, which determine a vasoconstriction of Small arteries and a proliferation of cells that coat the vessels with progressive narrowing of the same. When this happens the resistances in the vessels of the lung become greater than the resistances of the systemic circle and the passage of blood goes from the right heart, which has become more pressure, to the left heart. The reversal of blood flow results in the insertion of venous blood, not oxygenated, into the systemic circle and the patient becomes cyanotic. It is important to surgically repair congenital heart anomalies before these permanent changes in the pulmonary circle develop, because when this happened the defect can no longer be corrected.
IAP with impaired venularecapillare
More rarely is it associated with pulmonary arterial hypertension a picture of veno-occlusive disease in which the same remodeling of the Arteriolar district typical of pulmonary arterial hypertension involves the district of Small pulmonary veins. The recognition of this form is extremely important as it represents a contraindication to treatment with specific medications for pulmonary arterial hypertension for the risk of episodes of pulmonary edema.

Group II: Pulmonary hypertension secondary to left heart diseases
The left heart is made up of the left atrium, which collects the oxygenated blood from the lungs, and from the left ventricle, which pumping the blood inside the aorta provides oxygen and nutrients to all organs of the body. Several diseases both at the heart valves (mitral and aortic) and the left ventricle (systolic and/or diastolic dysfunction) can cause IP. These pathologies first cause an increase in blood pressure in the pulmonary veins, which carry oxygenated blood from the lungs to the left atrium, and secondarily in the pulmonary arteries. The use of specific medications for pulmonary arterial hypertension is not indicated In these forms, but treatment is limited to treating the dysfunction of the left heart.

III Group: Pulmonary hypertension Secondary to pulmonary parenchymal diseases
Emphysema, chronic bronchitis and pulmonary fibrosis are among the most frequent causes of IP, although fortunately they are less severe forms. These diseases secondarily involve the vascular part of the lung that is destroyed or transformed into fibrous tissue, reducing overall the number of functional blood vessels and causing an increase in pulmonary artery pressure. Therapy should aim to improve lung disease. In some cases the increased pressure in the pulmonary vessels is disproportionate to the lung disease. Therefore, studies are currently underway to assess the efficacy of specific drugs in these forms of pulmonary hypertension.

IV Group: Pulmonary hypertension secondary to pulmonary thromboembolism
Pulmonary thromboembolism is caused by the presence of blood clots (thromboembolism) within the vessels of the pulmonary circle. Usually the clots are formed in a vein of the legs and coming off arrive to the lungs, where they remain trapped in the vessels, hindering the passage of blood, resulting in increased pulmonary pressure. Various conditions favour the development of thrombus: trauma, surgical interventions, venous stasis, varicose veins, phlebitis, immobility, pregnancy, disabling diseases, congestive heart failure, hypercoagulation that can result from alterations of proteins of coagulation or the presence of certain antibodies or from the assumption of oral contraceptives (before the mid-1980s, when contraceptive pills contained a higher dose of hormones, pulmonary embolism was a more frequent risk), Malignant neoplasms. Usually the clots dissolve as a result of an appropriate therapy (anticoagulants). Only rarely will the patient develop the IP later.

V Group: Miscellaneous
It includes various types of diseases that have underlying molecular mechanisms different from each other: myeloproliferative disorders, sarcoidosis, neurofibromatosis, histiocytosis X, lymphangioleiomyomatosis, vasculitis, thyroid diseases and so on.