Pulmonary Hypertension: Causes

Pathogenesis (development of disease)

The cause of primary pulmonary hypertension (PH; pulmonary hypertension) is unknown. PH in left heart disease (group 2) represents the most common form of PH, accounting for up to 50% of all cases. PH due to pulmonary disease and/or hypoxia (group 3) represents the second largest PH group numerically (approximately 30-45%).

Etiology (Causes)

Biographic causes

  • Genetic burden: >80% of familial and >25% of sporadic PAH can be identified mutations/deletions of the bone morphogenetic protein receptor 2 gene (BMPR2) and 9 other genes in its signaling pathway; ALK1, endoglin mutations (with and without hereditary telangiectasia hemorrhagic)
    • Genetic diseases
      • Glycogen storage diseases – group of diseases with both autosomal dominant and autosomal recessive inheritance in which glycogen stored in body tissues cannot be degraded or converted to glucose, or only incompletely.
      • Gaucher disease – genetic disease with autosomal recessive inheritance; lipid storage disease due to the defect of the enzyme beta-glucocerebrosidase, which leads to the storage of cerebrosides, especially in the spleen and marrow-containing bones
      • Neurofibromatosis – genetic disease with autosomal dominant inheritance; belongs to the phakomatoses (diseases of the skin and nervous system); three genetically different forms are distinguished:
        • Neurofibromatosis type 1 (von Recklinghausen’s disease) – patients develop multiple neurofibromas (nerve tumors) during puberty, which often occur in the skin but also occur in the nervous system, orbita (eye socket), gastrointestinal tract (gastrointestinal tract), and retroperitoneum (space located behind the peritoneum on the back toward the spine); Typical is the appearance of café-au-lait spots (light brown macules) and multiple benign (benign) neoplasms
        • [Neurofibromatosis type 2 – characteristic is the presence of bilateral (bilateral) acoustic neuroma (vestibular schwannoma) and multiple meningiomas (meningeal tumors).
        • Schwannomatosis – hereditary tumor syndrome]
      • Sickle cell anemia (med.: drepanocytosis; also sickle cell anemia, sickle cell anemia) – genetic disorder with autosomal recessive inheritance affecting erythrocytes (red blood cells); it belongs to the group of hemoglobinopathies (disorders of hemoglobin; formation of an irregular hemoglobin called sickle cell hemoglobin, HbS).

Secondary pulmonary hypertension may be due to the following conditions. Biographical causes

Behavioral causes

Disease-related causes

Congenital malformations, deformities and chromosomal abnormalities (Q00-Q99).

  • Congenital vitia (congenital heart defects) [childhood most common].

Respiratory System (J00-J99)

  • Bronchial asthma
  • Chronic obstructive pulmonary disease (COPD)
  • Interstitial lung disease
  • Pulmonary emphysema – condition in which there is increased air in the lungs. However, the gas exchange area is decreased. The reason for this is a destruction of the parenchyma (lung tissue).
  • Pulmonary fibrosis – connective tissue remodeling of the lungs, which leads to the destruction of the lung structure.

Certain conditions originating in the perinatal period (P00-P96).

  • Persistent pulmonary arterial hypertension of the newborn.

Blood, hematopoietic organs – immune system (D50-D90).

Endocrine, nutritional and metabolic diseases (E00-E90).

  • Thyroid disorders, unspecified

Cardiovascular system (I00-I99)

  • Left heart disease, unspecified
  • Pulmonary embolism-partial (partial) or complete obstruction of a pulmonary artery
  • Chronic thromboembolism – chronic occlusion of pulmonary vessels by thrombi (blood clots).
  • Familial pulmonary arterial hypertension
  • Idiopathic pulmonary arterial hypertension (PAH) – form of the disease whose cause is unknown [childhood most common].
  • Mitral/aortic valve defect, unspecified.
  • Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH).

Infectious and parasitic diseases (A00-B99).

  • Schistosomiasis – worm disease (tropical infectious disease) caused by trematodes (sucking worms) of the genus Schistosoma (couple flukes).
  • HIV infection/AIDS

Liver, gallbladder and bile ducts – Pancreas (pancreas) (K70-K77; K80-K87).

Musculoskeletal system and connective tissue (M00-M99).

Neoplasms – tumor diseases (C00-D48).

  • Bronchial carcinoma (lung cancer)
  • Histiocytosis/Langerhans cell histiocytosis (abbreviation: LCH; formerly: histiocytosis X; Engl. histiocytosis X, langerhans-cell histiocytosis) – systemic disease with proliferation of Langerhans cells in various tissues (skeleton 80% of cases; skin 35%, pituitary gland (pituitary gland) 25%, lung and liver 15-20%); in rare cases, neurodegenerative signs may also occur; in 5-50 % of cases, diabetes insipidus (hormone deficiency-related disturbance in hydrogen metabolism, leading to extremely high urine excretion) occurs when the pituitary gland is affected; the disease occurs disseminated (“distributed over the whole body or certain regions of the body”) frequently in children between 1-15 years of age, less frequently in adults, here predominantly with an isolated pulmonary affection (lung affection); prevalence (disease frequency) approx. 1-2 per 100,000 inhabitants
  • Lymphangiomatosis – rare disease state characterized by diffuse proliferation of lymphatic vessels. This can affect internal organs, bones, soft tissues, and the skin
  • Myeloproliferative disorders
  • Pulmonary capillary hemangiomatosis (PCH) – occurrence of numerous benign vascular tumors.

Psyche – Nervous System (F00-F99; G00-G99).

Genitourinary system (kidneys, urinary tract – sex organs) (N00-N99).

Injuries, poisoning, and other sequelae of external causes (S00-T98).

  • Chronic altitude sickness

Medication

Other causes

  • Compression of pulmonary vessels – by tumors, foreign bodies, parasites, etc.
  • Condition following splenectomy (removal of spleen).