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

Pulmonary arterial hypertension
comprises:

Pulmonary Arterial
Hypertension in the
Idiopathic Pulmonary
setting of Collagen Portal Hypertension
Arterial Hypertension
Vascular Disease (e.g.
CREST syndrome)

Persistent pulmonary
Congenital left-to-right
Infection with HIV hypertension of the
intracardiac shunts
newborn

disease in Pulmonary Arterial Hypertension Harrison W. Farber, M.D., and Joseph

Fisiopatología
Cambios Histológicos
Mediadores de la respuesta a la PAH

Histological Findings

Intimal Fibrosis

Increased Medial Thickness

Pulmonary Arteriolar Occlusion

Plexiform Lesions

Vascular changes

Smooth-muscle
cell and
Vasoconstriction Thrombosis
endothelial-cell
proliferation


Mediators of Pulmonary Vascular
Responses
in 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

Diagnóstico
Datos Clínicos
Estudios de Laboratorio e Imagen

Clinical presentation
The symptoms of PAH are non- The physical signs of PAH
specific and include include
 Breathlessness  Accentuated pulmonary component of 2º hrt
sound
 Fatigue  Pansystolic murmur of tricuspid regurgitation
 Weakness  Diastolic murmur of pulmonary insufficiency

 Angina  RV third sound
 Jugular vein distension
 Syncope  Hepatomegaly
 Abdominal distension  Peripheral edema
 Ascites
Cool extremities
 Symptoms at rest are 

Lung sounds are usually normal
reported only in very 

Telangiectasia
advanced cases 

 Digital ulceration
 Sclerodactyly are seen in scleroderma
 The stigmata of liver disease such as spider
naevi, testicular atrophy, and palmar erythema
ESC Guidelines - Guidelines for the diagnosis should be considered
and treatment of pulmonary

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 hypertension
Prominent 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.

Pulmonary arterial hypertension

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