2. Introduction
• Definition :
• Pulmonary Hypertension is defined by a mean
pulmonary artery pressure more than or equal to 25
mmHg at rest.
• Pulmonary Artery Hypertension is characterised
hemodynamically by presence of pre capillary PH
including an end expiratory pulmonary wedge pressure
less than 15mmhg and a pulmonary vascular resistance
(PVR) more than 3 wood unit.
• Incidence of PH range between 2.4 and 7.6 cases per
million people.
• Prevalence estimates range between 15 and 26 cases
per million people.
3. Pathophysiology
• The pulmonary circulation normally is a high-
flow, low-resistance, low-pressure system.
• PAP is the product of cardiac output (CO) and
pulmonary vascular resistance (PVR), where
PVR is the vascular resistance of the entire
lung, including the pulmonary arteries,
capillaries, and veins.
4. Regulation of PVR
• Normal pulmonary artery pressure 25/10
mmHg
• mPAP 15 mmHh
• PVR in PA 2mmHg/lit/mt
• Increase in CO no effect on PAP in normal
Adult , due to recruitment of non perfused
vessels
• Exercise – increases CO
5. • NO, Endothelin 1 , prostaglandins , o2 plays important
role in maintaining PVR.
• Endothelin 1 –activates protien kinase c – causes
opening of calcium channel , increases intracellular
calcium.
• NO – stimulates gaunylate cyclase - inc. cGMP – dec
intracellular calcium.
• PGI2- activates adenylate cyclase – inc. cAMP- dec
calcium.
• Hypoxia – closes k+ channel – depolarisation of cell –
Ca2+ influx – vasoconstriction.
• Endothelin 1 increases NO while NO decreases
Endothelin1
10. Genetics of PAH
• Bone Morphogenic Protien (BMP) : it inhibits
proliferation and induces apoptosis of smooth muscle
cells.
• This ability of BMP is suppressed in cells isolated
specifically from smaller pulmonary vessels in patients
with IPAH.
• BMPR2 gene mutation : BMP receptor acts as receptor
both for BMP and TGFbeta. BMPR2 gene mutation is
found in 70% pt with familial PAH and 20% of pt with
IPAH.
• Others – activin receptor kinase-like 1 (ALK1), endoglin
(Eng), and Smad 8.
11.
12. Clinical features
• Mild breathlessness
• Dyspnoea on exertion
• Cough
• Fatigue
• Dizziness
• Swelling of leg
• Syncope , chest pain, palpitation
• Asymptomatic
13. World Health Organization Functional Classification of
Patients with Pulmonary Hypertension
• Class I: Patients with PH but without resulting limitation of
physical activity. Ordinary physical activity does not cause undue
dyspnea or fatigue, chest pain, or near syncope.
• Class II: Patients with PH resulting in slight limitation of physical
activity. They are comfortable at rest. Ordinary physical activity
causes undue dyspnea or fatigue, chest pain, or near syncope.
• Class III: Patients with PH resulting in marked limitation of physical
activity. They are comfortable at rest. Less than ordinary activity
causes undue dyspnea or fatigue, chest pain, or near syncope.
• Class IV: Patients with PH with inability to carry out any physical
activity without symptoms. These patients manifest signs of right
heart failure. Dyspnea and/or fatigue may even be present at rest.
Discomfort is increased by any physical activity.
14. • If PH is suspected or diagnosed , Patients should be
asked about important symptoms or risk factors that
might suggest cause of pulmonary hypertension. This
include
• symptoms of collagen vascular disease
• sleep apnea
• history of risks for thromboembolism, HIV infection,
liver disease, or anorectic agent use.
• A history of tobacco use and chronic sputum
production, or a known history of asthma with poor
control might be important clues to the presence of
obstructive airway disease and hypoxia as the cause of
pulmonary hypertension.
• A history of interstitial lung disease or any cause of
chronic hypoxia must be noted. A careful family history
should be taken.
15. Physical examination
• Cyanosis, raised JVP, pedal edema, ascites ,
pulsatile Hepatomegaly – indicates right heart
failure.
• CVS Examination – loud s2, ejection systolic
murmur, left parasternal heave, Rvs4
• Signs suggestive of moderate to sever PAH :
Pan systolic murmur of TR,Rvs3,
Hepatojugular reflex, invreased v wave of JVP,
hypotension, low pulse pressure.
16.
17. Diagnostic studies
• to confirm the presence of pulmonary
hypertension,
• identify the etiology,
• assess severity and prognosis, and
• to help guide appropriate therapy
21. Echocardiography
• Doppler examination is able to quantify the tricuspid
regurgitant jet in the majority of cases.
• A modified Bernoulli equation is used to estimate right
ventricular systolic (RVSP = 4v2 + right atrial pressure)
and is assumed equal to the pulmonary artery systolic
pressure.
• Normal RVSP has been reported as 28 ± 5 mm Hg.
• It may also identify cause of PH.
• Recent methods to evaluate RV function - tricuspid
annular plane systolic excursion, tissue Doppler
imaging, and myocardial performance index (Tei-
Doppler index).
22. • After diagnosis of PH is made next step to find
out cause of PH
• PFT
• V/Q scan
• Overnight pulse oxymetry or
polysomnography
24. Lab Testing
• HIV antibody,
• rheumatologic serologies (e.g., ANA),
• liver function tests, and
• complete blood count
• Exercise testing : 6MWT
25. Cardiac Catheterisation
• Right heart cardiac catheterization is required to
confirm the diagnosis of pulmonary hypertension, test
for important cardiac causes, and perform vasodilator
trials to determine an initial approach to therapy.
• LVEDP
• PAWP
• Blood gases
• Cardiac Output is obtained by either thermodilution or
use of measured arterial and venous hemoglobin
saturations and the Fick principle.
• The PVR is calculated as (mean PA pressure –
PCWP)/CO
26. • PH with normal PVR – inc. CO or postcapillary HTN,
• PH, elevated PVR, and a variable CO – portopulmonary
HTN.
• Acute vasodilator trial – it is only done in experimental
centres . Agents used areinhaled nitric oxide,
intravenous adenosine, or epoprostenol.
• a decrease in the mPAP of at least 10 mm Hg to a value
less than 40 mm Hg, together with a CO that is
unchanged or increased (but not decreased) is
generally considered a “positive” acute vasodilator
response.
27.
28. Treatment of PAH
GENERAL MANANGEMENT
• Exercise and the Avoidance of Deconditioning
• Oxygen Therapy
• Air Travel
• Immunizations
• Fluid Management and Diuretics
• Anticoagulation
• Contraception and Pregnancy
29. • PAH-SPECIFIC PHARMACOTHERAPY
• 1. calcium channel antagonist
• 2. Endothelin Receptor Antagonist
• bosentan
• ambrisentan, Sitaxsentan,
• 3. Specific inhibitors of phosphodiesterase type 5
(e.g., sildenafil, vardenafil, and tadalafil)
• Prostenoid Therapies : formulations available are
continuous intravenous infusion (epoprostenol and
treprostinil), subcutaneous infusion (treprostinil), and
via inhalation (treprostinil and iloprost).
30. • Epoprostenol therapy is initiated at 1 to 4 ng/kg/min and
progressively increased in 0.5 to 1 ng/kg/min increments at
intervals dictated by patient response and side effects.
• Treprostinil is initiated at 0.625 or 1.25 ng/kg/min and
similarly increased as dictated by clinical response, typically
in increments of 1.25 ng/kg/min
• Iloprost inhalational therapy is initiated at a dosage of 2.5
and increased to 5 μg with the subsequent dose if
tolerated.
• Treprostinil is started at 18 μg (3 breaths) four times a day,
with dose escalation suggested every 1 to 2 weeks to a
maximum and target dose of 54 μg (nine breaths) four
times daily.
• Prostenoid side effects are seen with inhalational therapy,
including headache, nausea, diarrhea, flushing, and jaw
discomfort.
Lung tansplantation
