Bài giảng dành cho sinh viên y khoa, bác sĩ đa khoa, sau đại học. ĐH Y Dược TP Hồ Chí Minh. Definition Causes Pathogenesis Pathophysiology Clinical Manifestations Natural History Diagnosis Management
PULMONARY HYPERTENSION Vu Minh Phuc MD CONTENTS Definition Causes Pathogenesis Pathophysiology Clinical Manifestations Natural History Diagnosis Management DEFINITION The normal pulmonary arterial pressure (PAP) of children and adults at sea level Systolic/diastolic PAP = 20/12 mm Hg Mean PAP (mPAP) = 15 mm Hg Pulmonary hypertension (PHTN) mPAP 25 mm Hg at rest mPAP 30 mm Hg during physical exercise CAUSES L-R shunt lesions (hyperkinetic PHTN) ASD, VSD, PDA, ECD Alveolar hypoxia Pulmonary parenchymal disease Extensive pneumonia Primary or secondary hypoplasia of lungs Bronchopulmonary dysplasia Interstitial lung disease (Hamman-Rich syndrome) Wilson-Mikity syndrome Upper and lower airway obstruction Inadequate ventilatory drive (central nervous system disease) Disorders of chest wall or respiratory muscles Kyphoscoliosis Weakening or paralysis of skeletal muscle High attitude (in certain hyperreactors) CAUSES Pulmonary venous hypertension Mitral stenosis, cor triatriatum, TAPVR with obstruction, chronic left heart failure, left-sided obstructive lesions (aortic stenosis, coarctation of the aorta) Primary pulmonary vascular disease Persistent pulmonary hypertension of the newborn Primary pulmonary hypertension – rare, fatal form of pulmonary hypertension with obscure cause Thromboembolism: ventriculoatrial shunt for hydrocephalus, sickle cell anemia, thrombophlebitis Collagen disease: rheumatoid arthritis, scleroderma, mixed connective tissue disease 3- PATHOGENESIS Endothelial dysfunction in PHTN 3- PATHOGENESIS Imbalance of vasoactive mediators acting on the pulmonary vessels 3- PATHOGENESIS P (pressure) = F (flow) R (resistance) F or R or both PHTN PHTN constriction of pulmonary arterioles PVR RV hypertrophy Normal RV cannot sustain sudden pressure loads over 40-50 mmHg acute right-sided heart failure if PVR increases abruptly Hypertrophied RV can tolerate mild PHTN (PAPs = 50 mmHg) Superimposed lung disease, alveolar hypoxia, acidosis RV may fail 3- PATHOGENESIS 3.1 Hyperkinetic pulmonary hypertension 3- PATHOGENESIS 3.2 Alveolar hypoxia 3- PATHOGENESIS 3.3 Pulmonary venous hypertension 3- PATHOGENESIS 3.4.Primary pulmonary vascular disease TREATMENT OF PULMONARY HYPERTENSION Milrinone PGE1 PGI2 Dobuta Isoprote PG B2 SMOOTH CELL ac ATP pde III cAMP inactive AMP ETA Vasodilation ET-1 Vasoconstriction ETB GTP NO NOr cGMP gc Ca++ A1 pde V Nitroprusside Nitroglycerin B2 Sildenafil Bonsentan Calcium Tolazoline blockers PGI2 ETB NO ET-1 L-citrullin L-arginine NO synthetase ENDOTHELIAL CELL ATP inactive GMP Sixtasentan Bonsentan Bonsentan ABBREVIATION A1: alpha receptors GMP: guanosine monophosphate AMP: adenosine monophosphate cGMP: cyclic GMP cAMP: cyclic AMP GTP: guanosine triphosphate ATP: adenosine triphosphate NOr: nitric oxide receptors B2: beta receptor PDE III: phosphodiesterase III ETA: ETA receptors on smooth cells PDE V: phosphodiesterase V ETB: ETB receptors on smooth cells PG: prostaglandin receptors and endothelial cells PGE1: prostaglandin E1 ET-1: endothelial-1, an isopeptide PGI2: prostacyclin produced primarily in the vascular endothelial cells PULMONARY VASODILATORS Oxygen, Nitric oxide Prostacyclin Epoprostenol, Ventavis (IV) Iloprost (aerosol) Anti-acidosis Adenosine (IV) Amrinone, Milrinone L-arginine (IV) Sildenafil Dobutamin (IV) Bonsentan Isoproterenol (IV) Sixtasentan Tolazoline (IV) Calcium blockers (nifedipine, Nitroprusside (IV) Nitroglycerine (IV) diltiazem) Salbutamol PULMONARY VASODILATOR TREATMENT - mPAP > ½ mSBP and/or - Increasing PAP causes tachycardia and falling toe temperature - NO - Epoprostenol/ Ventavis YES Acute vasodilator response Trial of calcium chanel blckers (nifedipine or diltiazem) NO Incomplete response NO Right heart failure Trial of: - Iloprost - Sildenafil YES - Bonsentan se n o sp e r - Sixtasentan lete p Epoprostenol - Investigational drugs om Inc ... 20/12 mm Hg Mean PAP (mPAP) = 15 mm Hg Pulmonary hypertension (PHTN) mPAP 25 mm Hg at rest mPAP 30 mm Hg during physical exercise CAUSES L-R shunt lesions (hyperkinetic PHTN) ASD,... increases abruptly Hypertrophied RV can tolerate mild PHTN (PAPs = 50 mmHg) Superimposed lung disease, alveolar hypoxia, acidosis RV may fail 3- PATHOGENESIS 3.1 Hyperkinetic pulmonary hypertension... coarctation of the aorta) Primary pulmonary vascular disease Persistent pulmonary hypertension of the newborn Primary pulmonary hypertension – rare, fatal form of pulmonary hypertension with obscure