PULMONARY
HYPERTENSION
• Normal mean pulmonary artery pressure = 10–14 mm Hg
• Pulmonary hypertension (PH) if:
• ≥ 25 mmHg at rest
• ≥ 30 mmHg during exercise/exertion
• The range of genetic, molecular, and humoral causes that
can lead to this increase in pressure is extensive
• Therefore, WHO has grouped PH into different classes that
are based on clinical and pathological findings as well as
therapeutic interventions
• Vascular remodelling
• Ultimate result = narrowed lumen = PH
• Endothelial disruption/damage
• Intimal fibrosis (stiffening – potentially TGF-
B-mediated)
• Neointimal proliferation – movement of
smooth muscle cells into the intimal layer
• Medial hypertrophy due to proliferation of
smooth muscle cells in tunica media
• Plexiform lesions (characteristic)
Idiopathic = Unknown etiology
> Endothelial dysfunction resulting in an
imbalance between vasoconstrictors (e.g,
endothelin) and vasodilators (NO and
prostacyclins).
> Heritable PAH can be due to an inactivating
mutation in BMPR2 gene (normally inhibits
vascular smooth muscle proliferation); poor
prognosis
Vascular remodelling in pulmonary arterial hypertension.
Haematoxylin-and-eosin staining showing:
(A) neointimal proliferation (double arrow) in an elastic pulmonary artery,
(B) medial hypertrophy and neointimal proliferation leading to occlusion of the
vessel lumen (arrows) in muscular pulmonary arteries
(C) a plexiform lesion, comprising a plexus of capillary-like channels
plexiform lesion = tuft of capillary formations
produces a network, or web, that spans the lumens of
dilated thin-walled, small arteries and may extend
outside the vessel
> Characteristic for PH
Example: Scleroderma (systemic sclerosis)
• Autoimmune disorder characterized by sclerosis of
skin and visceral organs
• Classically presents in middle-aged females (30-50
years)
• Limited type (skin and face)
• Diffuse type – any organ involved
• Autoimmune damage to mesenchyme
= initiating event
• Endothelial cell dysfunction
• Inflammation
• Secretion of TGF- and PDGF
• Fibroblast activation and deposition of collagen
• Organ damage
• LUNGS = interstitial fibrosis and HTN
Group 2 = Left heart failure and valvular
diseases
• Systolic dysfunction = increased ESV =
increased pressure in ventricle atrium
pulmonary vasculature
• Diastolic dysfunction = decreased filling =
increased volume and pressure in left atrium =
back-up into pulmonary vasculature
• Mitral valve stenosis or regurgitation
Group 3: Lung disease or hypoxia
• Damage to alveoli = Hypoxia – induced
vasoconstriction = PH
• Lung diseases – same toxins or particles that
damage alveoli can damage endothelium –
triggers inflammatory response and vascular
remodelling
Group 4: Chronic thromboembolic PH
• Microthrombi form and obstruct pulmonary
vessels
• Can treat with thrombolytics
Symptoms and clinical presentation:
• Exertional dyspnea (trouble
breathing); chest pain
• Fatigue
• Syncope
Signs of Right Heart
Failure
• JVD
• Peripheral Edema; ascites
• Liver enlargement leading
to right upper quadrant
pain
Among healthy individuals,
the average 6MWD is between
400 and 700 meters.
X-RAY
Right heart catheterization
Port of entry:
• jugular vein or
femoral vein
Measurement of RA,
RV and PA pressures
