pulmonary arterial hypertension

PULMONARY ARTERIAL HYPERTENSION

Allan Murillo – Médico Interno - UNICAH

Definition

PAH is defined as a sustained elevation of pulmonary arterial pressure to more than 25 mm Hg at rest or to more than 30 mm Hg with exercise, with a mean pulmonary-capillary wedge pressure and left ventricular end-diastolic pressure of less than 15 mm Hg

Puede ser consecuencia de insuficiencia en la mitad izquierda del corazón, enfermedad del parénquima o de vasos pulmonares, tromboembolia o una combinación de tales factores

NEJM 351;16 www.nejm.org october 14, 2004 - Review Article - Mechanisms of disease in Pulmonary Arterial Hypertension Harrison W. Farber, M.D., and Joseph Loscalzo, M.D., Ph.D.

Pulmonary arterial hypertension comprises:

Idiopathic Pulmonary

Arterial Hypertension

Pulmonary Arterial

Hypertension in the setting of

Collagen Vascular Disease (e.g.

CREST syndrome)

Portal Hypertension

Congenital left-to-right

intracardiac shunts

Infection with HIV

Persistent pulmonary

hypertension of the newborn


Cambios HistológicosMediadores de la respuesta a la PAH

Fisiopatología

Histological Findings

Intimal Fibrosis

Increased Medial ThicknessPulmonary Arteriolar Occlusion

Plexiform LesionsNEJM 351;16 www.nejm.org october 14, 2004 - Review Article - Mechanisms of disease in Pulmonary Arterial Hypertension Harrison W. Farber, M.D., and Joseph Loscalzo, M.D., Ph.D.

Vascular changes

VasoconstrictionSmooth-muscle cell and endothelial-cell

proliferationThrombosis


Mediators of Pulmonary Vascular Responsesin Pulmonary Arterial Hypertension Thromboxane A2 Prostaglandin I Nitric oxide Endothelin-1 Serotonin Vascular Endothelial Growth Factor Vasoactive Intestinal Peptide


Prostacyclin/Thromboxane A2 Prostacyclin: potent vasodilator, inhibits platelet

activation and has antiproliferative properties Thromboxane A2 is a potent vasoconstrictor and

platelet agonist.

In PAH, the imbalance between these two molecules is shifted toward thromboxane A2.

The production of prostacyclin synthase is decreased in the small and medium-sized pulmonary arteries of patients with pulmonary hypertension, particularly those with idiopathic PAH


Endothelin-1

Potent vasoconstrictor, stimulates proliferation of pulmonary-artery smooth-muscle cells

The plasma levels of endothelin-1 are increased in PAH and the level of endothelin-1 is inversely proportional to the magnitude of the pulmonary blood flow and cardiac output


Nitric Oxide

Potent vasodilator and inhibitor of platelet activation and vascular smooth-muscle cell proliferation

Decreased levels of nitric oxide synthase have been observed in the pulmonary vascular tissue of patients with idiopathic PAH

Endothelial nitric oxide synthase is, howerver, increased in the plexiform lesions of idiopathic PAH, where it probably promotes pulmonary endothelial-cell proliferation


Serotonin

Vasoconstrictor that promotes smooth-muscle cell hypertrophy and hyperplasia.

↑ levels of plasma serotonin and ↓ content of serotonin in platelets have been found in idiopathic PAH and persist even after the normalization of pulmonary-artery pressures following lung transplantation.

The level of serotonin itself is probably not a determinant of pulmonary hypertension, because selective serotonin- reuptake inhibitors (SSRIs), which increase serotonin levels but inhibit serotonin transport, are not associated with an increased incidence of pulmonary hypertension and may, in fact, be protective in the setting of hypoxia


Adrenomedullin

Dilates pulmonary vessels, increases the pulmonary blood flow, and is synthesized by several cell populations in the normal lung

The plasma levels of adrenomedullin are elevated in both PAH and PH associated with hypoxemia, and the elevation correlates with increases in the mean right atrial pressure, pulmonary vascular resistance, and the mean pulmonary arterial pressure.

Current data suggest that increased adrenomedullin is a marker of PH, rather than a cause.


Vasoactive Intestinal Peptide Potent systemic vasodilator, decreases

pulmonary-artery pressure and pulmonary vascular resistance; it also inhibits platelet activation and vascular smooth-muscle cell proliferation.

A recent study reported decreased levels of vasoactive intestinal peptide in the serum and the lungs in patients with PAH; treatment with inhaled vasoactive intestinal peptide improved the clinical course and the hemodynamics in these patients.


Vascular Endothelial Growth Factor

In acute and chronic hypoxia, the production of vascular endothelial growth factor (VEGF) is increased and that of its receptors, VEGF receptor-1 and VEGF receptor-2 in the lung

In PAH, disordered angiogenic responses appear to underlie the formation of plexiform lesions and the clonal expansion of endothelial cells within the lesions

There is an imbalance of the vascular effectors in PAH that favors vasoconstriction, vascular-cell proliferation, and thrombosis


ESC Guidelines - Guidelines for the diagnosis and treatment of pulmonary hypertension - European Heart Journal (2009) 30, 2493–2537

Datos ClínicosEstudios de Laboratorio e Imagen

Diagnóstico

Clinical presentation

Breathlessness Fatigue Weakness Angina Syncope Abdominal distension

Symptoms at rest are reported only in very advanced cases

Accentuated pulmonary component of 2º hrt sound

Pansystolic murmur of tricuspid regurgitation

Diastolic murmur of pulmonary insufficiency

RV third sound Jugular vein distension Hepatomegaly Peripheral edema Ascites Cool extremities Lung sounds are usually normal Telangiectasia Digital ulceration Sclerodactyly are seen in scleroderma The stigmata of liver disease such as

spider naevi, testicular atrophy, and palmar erythema should be considered

The symptoms of PAH are non-specific and include

The physical signs of PAH include


Electrocardiogram

The ECG may provide suggestive or supportive evidence of PH: RV hypertrophy on ECG is present in 87% and right axis

deviation in 79% of patients with IPAH

Supraventricular arrhythmias may be present in advanced stages, in particular atrial flutter, but also atrial fibrillation, which almost invariably leads to further clinical deterioration.

BRDHH de grado avanzado

The absence of these findings does not exclude the presence of PH nor does it exclude severe haemodynamic abnormalities.


Chest radiograph

In 90% of patients with IPAH the chest radiograph is abnormal at the time of diagnosis.

Findings include: Central pulmonary arterial dilatation Right atrium and RV enlargement in

advanced cases.


Severe pulmonary hypertensionProminent main pulmonary artery segment (MPA), which appears to be aneurysmally dilated. Right pulmonary artery (RPA) is also enlarged.

En la PAH no se puede observar la presencia de vasos sanguineos en la periferia pulmonar

Pulmonary function tests and Arterial Blood Gases

Patients with PAH usually have decreased lung diffusion capacity for carbon monoxide and mild to moderate reduction of lung volumes

PAO2 is normal or only slightly lower than normal at rest and PACO2 is decreased because of alveolar hyperventilation


Echocardiography

Transthoracic echocardiography provides several variables which correlate with right heart haemodynamics including PAP, and should always be performed in the case of suspected PH


High-resolution CT


Provides detailed views of the lung parenchyma and facilitates the diagnosis of interstitial lung disease and emphysema.

Characteristic changes of interstitial oedema with diffuse central ground-glass opacification and thickening of interlobular septa suggest PVOD; additional findings may include lymphadenopathy and pleural effusion.

Pulmonary capillary haemangiomatosis is suggested by diffuse bilateral thickening of the interlobular septa and the presence of small, centrilobular, poorly circumscribed nodular opacities.

FIN … WUJU!!!

pulmonary arterial hypertension

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