Pulmonary Circulation

M. Rizki Akbar
Department of Cardiology and Vascular Medicine
Faculty of Medicine, Universitas Padjadjaran
BANDUNG
Pulmonary Circulation
 Pulmonary Circulation
Systemic Circ. Pulmonary Circ.
C.O. (L/min) 6.0 ≈ 5.9

Arterial B.P. (mm Hg) 100 >> 15

Venous B.P. (mm Hg) 2 “≈” 5

Vascular resistance (∆P/flow) 100-2/6=16.3 > 15-5/5.9=1.7

Vascular compliance (∆V/∆P) Csystemic << Cpulm

 Pulmonary Circulation
4 function :
1. Blood reservoir (500 ml = 10%)
2. Gas exchange
3. Metabolic organ
4. Blood filter

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 Specifics of the
Pulmonary Circulation
 Function (O2 into blood)
 ~ whole cardiac output
 Capillaries surrounded by air  no support
against intravascular pressure  pressure has to
be low
 High flow at low pressure  low vascular
resistance:
 thin wall (high compliance)
 minimal resting tone
 short vessels
 Smooth muscle cells

Endothelium

Intermediate cell Pericyte

Partly
Muscularized muscularized Non-muscularized
vessel vessel vessel
Pulmonary vessels are more
Q rrueai cpnke
G
a hTieci dm
s eedd™ c oasm
e to nedperaethsi ss opr i c tu r e .

distensible than systemic

250000
Aorta
Tenze 200000
Tension
(dyn/cm)
(dyn/cm)

150000
Pulmonary
trunk
Plícnice
100000

50000

0
0 10 20 30 40 50
Extenze (%)
Extension (%)
Pulmonary blood vessels are much more compliant than systemic blood vessels.
Also the system has a remarkable ability to promote a decrease in resistance as the
blood pressure rises.
Two reasons are responsible:
Recruitment: opening up of previously closed vessels
Distension: increase in caliber of vessels
 Gas exchange at alveolar and systemic capillaries
Inspired air:
Expired air:
PO2 = 158 mm Hg
PO2 = 116 mm Hg
PCO2 = 0.3 mm Hg
PCO2 = 32 mm Hg

Right Heart Left Heart

Arterial blood
PO2 = 95 mm Hg
PCO2 = 41 mm Hg
(physiological shunt)
 Matching respiration & blood flow: the Ventilation-
Perfusion Ratio

Ventilation
Alveolar ventilation, VA
VA = (VT - VD) x resp. rate
= (0.5 - 0.15) x 12 = 4.2 L/min

Perfusion
Cardiac output = C.O. = Q
Q = stroke vol. x heart rate
= (0.086) x 70 = 6.0 L/min

VA
= ventilation/perfusion ~ 0.8
Q
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Let’s assume that there is a blockage of one alveolar region

VA << 0.8 VA
~ 0.8
Q
Q
 Other functions of the
pulmonary vascular bed
 Metabolic
 ACE
 removal of BK, ET, 5-HT...

 Blood filtering emboli

 PAP at rest  only when >30% obstructed
Pulmonary Hypertension

M. Rizki Akbar
Department of Cardiology and Vascular Medicine
Faculty of Medicine, Universitas Padjadjaran
BANDUNG
 Pulmonary Hypertension
 Defined as pressure within the pulmonary
arterial system elevated above the normal
range.
 mPAP greater than 25 mm Hg at rest or 30
mm Hg with exercise
 Pulmonary arterial pressure (PAP)
 usually 12-15 mmHg
 Left atrial pressure
 6-10 mmHg
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 Pulmonary Hypertension
 Pulmonary hypertension develops when
flow or resistance to flow across the
pulmonary vascular bed increases
 Hallmark of PAH pathogenesis:
Pulmonary arterial obstruction by
vascular proliferation and remodelling
 Not a disease, but a syndrome in which
the pressure in the pulmonary circulation
is raised.
18
 Pulmonary Hypertension
Revised WHO Clinical Classification of Pulmonary Hypertension
( Venice 2003 )
1. Pulmonary Arterial Hypertension ( PAH )
1.1 Idiopathic ( IPAH )
1.2 Familial (FPAH)
1.3 Associated with (APAH)
1.3.1 Collagen Vascular disease
1.3.2 Congenital systemic-to-pulmonary shunts
1.3.3 Portal hypertension
1.3.4 HIV infection
1.3.5 Drugs and toxins
1.3.6 Other ( Thyroid disorders, Glycogen storage disease,
Gaucher disease, Hereditary Hemorrhagic
Telangiectasia, Hemoglobinopathies, Myeloproliferative
disorders, splenectomy)
1.4 Associated with significant venous or capillary involvement
1.4.1 Pulmonary veno-occlusive disease ( PVOD )
1.4.2 Pulmonary capillary hemangiomatosis ( PCH )
1.5 Persistent pulmonary hypertension of the newborn
 Pulmonary Hypertension

2. Pulmonary hypertension with left heart disease

2.1 Left sided atrial or ventricular heart disease
2.2 Left sided valvular heart disease

3. Pulmonary hypertension associated with lung disease and/or

hypoxemia
3.1 Chronic obstructive pulmonary disease
3.2 Interstitial lung disease
3.3 Sleep disordered breathing
3.4 Alveolar hypoventilation disorders
3.5 Chronic exposure to high altitude
3.6 Developmental abnormalities
 Pulmonary Hypertension

4. Pulmonary hypertension due to chronic thrombotic and/or embolic

disease
4.1 Thromboembolic obstruction of proximal pulmonary arteries
4.2 Thromboembolic obstruction of distal pulmonary arteries
4.3 Non-thrombotic pulmonary embolism (tumor, parasites,
foreign materials)

5. Miscellaneous
Sarcoidosis, Histiocytosis X, Lymphangiomatosis, compression
of pulmonary vessels (adenopathy, tumor, fibrosing
mediastinitis)
 WHO Classification
Pulmonary arterial Chronic
hypertension hypoxemia

Left heart
Thrombo disease
embolic

Miscellaneous : Sarcoid, fibrsosing, mediastinitis

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 Chronic pulmonary hypertension is an
important cause of right ventricular failure
in the United States.

 Many of the individuals who die each year

of chronic obstructive pulmonary disease
(COPD) succumb secondarily to right
ventricular failure resulting from pulmonary
hypertension.

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 In addition, greater than 200,000 deaths
occur yearly from acute pulmonary
embolism, the most common cause of
sudden-onset pulmonary hypertension
and acute right ventricular failure.

 In persons more than 50 years of age, Cor

pulmonale the consequence of untreated
pulmonary hypertension, is the third most
common cardiac disorder (after coronary
and hypertensive heart disease).
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Pathogenesis of PAH

Gaine S. J Am Med Assoc 2000;284:3160-68

 Vascular Changes in PAH

 Vasoconstriction
 Smooth muscle cell and endothelial cell
proliferation
 Thrombosis

Farber, et al, NEJM 2004

 Genetic Predisposition Risk Factors
BMPR2 mutations Anorexigens
ALK1 mutations HIV Infections
5HTT polymorphisms ↑ Pulmo bld flow
ecNOS polymorphism Portal HPN
CPs polymorphisms CTD

Pulmonary Vascular Damage

Matrix changes
Platelets & Infl’ory cells Endothelial Dysfunction SMC Dysfunction
Activation

Vasoconstriction Proliferation

Thrombosis Inflammation

↑ PVR ↑ PAP

Pulmonary Hypertensive Vascular Disease

Initiation and Progression
 Schematic Progression of PAH

Pre-symptomatic/ Symptomatic/ Declining/

Compensated Decompensating Decompensated

CO
Symptom Threshold

PAP Right Heart

Dysfunction
PVR
PAP Time
CO =
PVR
What are we looking for ?
 Entities that cause increased
pulmonary blood flow

 Congenital Heart Disease

 Left to right shunt
 “Hyperkinetic" pulmonary hypertension can be
seen in patients with congenital heart disease who
have extensive left-to-right cardiac shunts that
produce a large pulmonary blood flow
 Increased cardiac output states
 severe anemias

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Entities that cause an increased
resistance to flow
 Pulmonary embolism
 In situ pulmonary embolism
 Pulmonary fibrosis
 Sarcoidosis, scleroderma, or extensive
pulmonary resection
 Severe COPD
 Thoracic deformities
 Large tumor or infiltrate
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 Entities that cause changes in
arterioles

 Hypoxia (altitude)
 COPD
 Hypoventilation (sleep apnea)
 Acidosis
 Drugs
 Pulmonary arterial hypertension (PAH)

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 Entities that cause venous
pressure changes & vascular
resistance
 Left atrial hypertension = Mitral Stenosis
 Left ventricular failure
 Pulmonary venous thrombosis
 Mediastinitis

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 Pulmonary Hipertension
 Elevated pulmonary venous pressure in
the setting of left ventricular failure or
mitral stenosis is associated with an
immediate increase in pulmonary arterial
pressure which maintains forward blood
flow through the lungs despite the
increase in pulmonary venous pressure.

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 Entities that increase blood
viscosity

 Polycythemia vera
 Leukemias with high WBC’s

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 Entities that increase intra-
thoracic pressure

 COPD
 Mechanical Ventilation: especially with
PEEP

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 Symptoms and Signs of PAH

 Vague and are often missed

 Symptoms associated with PAH

 Mild to moderate pulmonary hypertension

are often asymptomatic
 Shortness of breath (> 75%)
 Syncope (< 50%)
 Chest pain (> 50%)
 Symptoms of RH dysfunction
 Breathlessness (> 75%)
 Ascites
 Ankle swelling (< 50%)
 Anorexia
 Signs associated with PAH

 Loud split P2 (>80%)

 RV hypertrophy – RV lift (>80%)
 Increased “a” waves
 Increased “v” waves
 Diastolic murmur (pulmonary valvular
regurgitation) – severe PAH (< 50%)
 Pansystolic murmur (tricuspid
regurgitation) (50-80%)
 Signs of Right Heart Failure

 Poor peripheral perfusion (< 10%)

 Raised RA pressure – JVD (50-80%)
 RV 3rd and 4th heart sounds (< 50%) - (50-
80%)
 Tricuspid regurgitation (50-80%)
 Ejection systolic murmur across the
pulmonary valve (< 50%)
 Hepatomegaly (< 50%)
 Ascites, and/or peripheral edema (< 50%)
 Caveats
 Patients with severe emphysema and
increased thoracic anteroposterior
diameter may not display the findings
usually associated with advanced
pulmonary hypertension because chest
expansion make palpation and
auscultation more difficult.
 The JVD may actually be above the jaw-
line!
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 Pulmonary Arterial
Hypertension (PAH)

 Incurable disease characterized by medial

hypertrophy, intimal fibrosis and in situ
thrombi
 Very rare
 1-2 cases per million
 Age 34-36 & again 50-59
 Females>males (1.7:1)
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 Causes of PAH
 Unknown (IPAH)
 HIV
 Drugs
 Appetite suppressants(fenfluramine and
dexfenfluramine)
 Amphetamines
 Cocaine

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 ACCP Evidence- Based
Clinical Practice Guidelines
 Screening, Early Detection and Diagnosis
of Pulmonary Arterial Hypertension
 Genetic Testing

 Genetic testing and professional genetic

counseling should be offered to relatives
of patients with FPAH.
 ACCP: QOE: Expert opinion; Benefit: intermediate; SOR: E/A

 Patients with IPAH should be advised

about the availability of genetic testing and
counseling for their relatives.
ACCP:QOE: Expert opinion; Benefit: intermediate; SOR: E/A
 Chest X-ray

 In patients with suspicion of PAH, a Chest

x-ray should be obtained to reveal features
supportive of the diagnosis of PAH and to
lead to diagnoses of underlying diseases.
ACCP: QOE: low; Benefit: intermediate; SOR: C
 Chest X-ray in PAH

 Enlargement of the right side of the heart

Enlargement of the main PA
Enlargement of both hila due to enlarged PA
Loss of vascularity of the peripheral lung
Loss of retrosternal space on lateral view due to RVE
 Chest X-ray

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 Chest X-ray & EKG

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 Electrocardiogram

 In patients with PAH, ECG should be

performed to screen for a spectrum of
cardiac anatomic and arrhythmic
problems; it lacks sufficient sensitivity to
serve as an effective screening tool for
PAH, but contributes prognostic
information in patients with known PAH.
ACCP: QOE: low; Benefit: small/ weak; SOR: C
 EKG in PAH
 Large P wave on Lead II
 RAD
 Tall R waves and ST depression in right sided
chest leads
 RVH and strain
 S wave in lead I
 Q wave/ inverted T in Lead III
 RBBB
 Sensitivity 55%
 Specificity 70%
EKG
 2D Echocardiogram

 2D Echo should be performed as a

noninvasive screening test that can detect
PH, though it can be imprecise in
determining actual pressures compared to
invasive evaluation in a portion of patients.
ACCP: QOE: fair; Benefit: substantial; SOR:A
 2D Echocardiogram
 2D Echo should be performed to evaluate the
level of RVSP and to assess the presence of
associated anatomic abnormalities such as
RAE, RVE and pericardial effusion.
ACCP: QOE: Expert opinion; Benefit: intermediate; SOR: E/B

 In asymptomatic patients at high risk, 2D Echo

should be performed to detect PAP.
ACCP: QOE: Expert opinion; Benefit: intermediate; SOR: E/B
 2 D- Echocardiography in PAH

 Increased sPAP or TR
jet 2.8 m/s at rest
IVS
 Right atrial & ventricular
RV
hypertrophy LV
 Flattening of
intraventricular septum RA
LA
 Small LV dimension
 Dilated PA
 TIPG > 30 mm Hg
 2 D- Echocardiography in PAH

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 Mean PAP in PAH

 Mild PAH 25 – 40 mmHg

 Moderate PAH 41 – 55 mmHg
 Severe PAH > 55 mmHg
 Transesophageal Echocardiography (TEE)

 Useful in detection of intracardiac shunts,

especially ASD and detect central
pulmonary emboli
 Sensitivity 80 -96 %
 Specificity 88%
 V/Q Scan

 In patients with PAH, V/Q scanning should

be performed to rule out CTEPH; a normal
scan result effectively excludes a
diagnosis of CTEPH.
ACCP: QOE: low; Benefit: substantial; SOR: B
Ventilation / Perfusion Scan (V/Q scan)

 Heterogenous
perfusion with
multiple small
mismatched perfusion
defects in IPAH
 One segmental sized
or larger perfusion
defects in CTEPH
 Sensitivity 90 - 100%
 Specificity 94 -100%
 Right Heart Catheterization

 A RHC is required to confirm the presence

of PH, establish the specific diagnosis,
determine the severity of PH.
ACCP: QOE: good; Benefit: substantial; SOR: A

 RHC is required to guide therapy.

ACCP: QOE: low; Benefit: substantial; SOR: B
Right Heart Catheterization

 Required to confirm
diagnosis of PAH
 Measures CO by
Thermodilution or Fick to
calculate for PVR
 mPAP > 25 mmHg at rest
and > 30 mmHg with
exercise
 PCWP or LVEDP < 15
mmHg
 PVR > 3 wood units
 Vasoreactivity Tests

 Aim:
 To detect the residual properties of
vasodilatation of small pulmonary arteries and
arterioles and to differentiate this reversible
component from fixed obstructive changes.
 Vasoreactivity Testing
 Performed under
hemodynamic monitoring
 Minimum acceptable
response is reduction in
mPAP of 15-20% or at
least 10 mmHg from
baseline to reach a
mPAP < 40 mmHg, with
no change or increase
in cardiac output
 Predicts hemodynamic
response to long term
CCB and better prognosis
 Vasoreactivity Testing

Drug Route Half-life Dose Increase Duration

Range Dosage (min)
Prostacyclin IV 3 min 2-16 2 10
ng/kg.min ng/kg.min
Adenosine IV 5 – 10 s 50-200 20 2
ng/kg.min ng/kg.min
Nitric Oxide Inhaled 15 – 30 s 10-60 Not 5 – 10
ppm needed
Iloprost Inhaled 30 min 8-10 ug Not 10
needed
 Pulmonary Angiography

 In patients with PAH and a V/Q scan

suggestive of CTEPH, pulmonary
angiogram is required for accurate
diagnosis and best anatomic definition to
assess operability.
ACCP: QOE: Expert opinion; Benefit: substantial; SOR: E/A
Pulmonary Angiography

 DSA
 In PAH, abrupt
peripheral vascular
pruning
 Required to confirm
CTEPH and assess
operability
 Contrast-enhanced CT, MRI

 In patients with PAH, contrast enhanced

CT or MRI should not be used to exclude
the diagnosis of CTEPH.

ACCP: QOE: low; Benefit: negative; SOR: D

 Helical CT in PH

 Small areas of
centrilobular
attenuation clearly
visible relative to
areas of
vasoconstriction
 No interlobular septal
thickening
 PFT, ABG

 In patients with PAH, testing of pulmonary

function and arterial blood oxygenation should
be performed to evaluate for the presence of
lung disease.
ACCP: QOE: low; Benefit: substantial; SOR: B

 In patients with systemic sclerosis, PFT with

DLCO should be performed periodically ( q 6-12
months) to improve detection of pulmonary
vascular or interstitial disease.
ACCP: QOE: fair; Benefit: intermediate; SOR: B

DLCO = carbon monoxide diffusing capacity

 6 Minute walk Testing

 In patients with PAH, serial determinations

of functional class and exercise capacity
assessed by the 6 minute walk test
provide benchmarks for disease severity,
response to therapy, and progression.
ACCP: QOE: good; Benefit: intermediate; SOR: A
 Lung Biopsy

 In patients with PAH, lung biopsy is not

routinely recommended because of the
risk, except under circumstances in which
a specific question can only be answered
by tissue examination.
ACCP: QOE: good; Benefit: substantial; SOR: A
 Pulmonary arterial histologic lesions seen in
clinically unexplained pulmonary hypertension.

a. Medial hypertrophy
b. Concentric luminal intimal
a b fibrosis
c. Plexiform lesion
d. Eccentric intimal fibrosis

c d
Circulation Nov. 1989
 WHO Classification of Functional Status
of Patients with PH
Class Description
I Patients with PH in whom there is no limitation of usual physical
activity; ordinary physical activity does not cause increased
dyspnea, fatigue, chest pain, or presyncope.
II Patients with PH who have mild limitation of physical activity.
There is no discomfort at rest, but normal physical activity causes
increased dyspnea, fatigue, chest pain, or presyncope.
III Patients with PH who have a marked limitation of physical activity.
There is no discomfort at rest, but less than ordinary activity
causes increased dyspnea, fatigue, chest pain, or presyncope.
IV Patients with PH who are unable to perform any physical activity
at rest and who may have signs of right ventricular failure.
Dyspnea and/or fatigues may be present at rest, and symptoms
are increased by almost any physical activity.
Chest 2004:126 (Suppl), JACC 2004:43 (Suppl)
 Treatment Goals in PAH

 Improved exercise capacity

 Improved function
 Improved hemodynamics
 Improved survival
 Prevention of clinical worsening
 Treatment Algorithm

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Therapy Targets for PAH

Humbert M, Sitbon O, Simonneau G. N Engl J Med 2004;351:1425-36

Targeting the Mechanism of PAH
 Therapy of
Pulmonary Hipertension
 Treat the cause!
 Phosphodiesterase inhibitors (sildenafil)
 Prostanoids (prostacyclin analogues)
 Endothelin receptor antagonis
 Vasodilators
 Coumadin

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 Tx of Pulmonary HTN

 Phosphodiesterase inhibitors (sildenafil)

• Viagra
 Nitric oxide stimulation of endothelium
increases cGMP resulting in vasorelaxation
 Phosphodiesterase breaks down cGMP

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 Tx of Pulmonary HTN

 Prostanoids (prostacyclin analogues)

• Flolan, Iloprost
 Prostacyclin is a potent vasodilator produced
in the vascular endothelium . Also inhibits
growth of smooth muscle cells

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 Tx of Pulmonary HTN

 Endothelin receptor antagonists

• Bosentan
 Endothelan-1 is a potent vasoconstrictor,
induces fibosis and leads to proliferation of
smooth-muscle cells

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 Tx of Pulmonary HTN
 Treatment of heart failure (e.g., diuretics)
 Oxygen supplementation is indicated for rest, exercise,
or nocturnal hypoxemia
 Calcium channel blockers (nifedipine, diltiazem
 Only in selected patients that qualify via a

vasoreactivity study.
 Digoxin (afterload reduction & increase cardiac output)
 Surgery of thrombolic emboli
 Low salt diet
 Cautious exercise
 Heart-lung transplant

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 Nitric Oxide

 Inhaled form
 Acts as direct smooth
muscle relaxant via
activation of the
guanylate cyclase system
 Short therapeutic half life
 Ameliorates hypoxemia
and lowers PVR by direct
pulmonary vasodilatation
 Anticoagulation

 Rationale for use is based on the

presence of traditional risk factors for VTE,
such as heart failure and sedentary
lifestyle, thrombophilic predisposition,
thrombotic changes in the pulmonary
microcirculation and in the elastic
pulmonary arteries.
 Dose adjusted according to INR 2 - 3
 Supplemental Oxygen

 Low mixed venous

oxygen saturation caused
by low cardiac output and
low minimally altered
ventilation/ perfusion
matching.
 Improves quality of life
and ↓ mortality in patients
with PH due to chronic
respiratory insufficiency.
 Surgical Interventions

 Atrial Septostomy
 Allow R L shunting to increase systemic output
that, in spite of fall in the systemic arterial
oxygen saturation, will produce an increase in
systemic oxygen transport.
 Shunt at the atrial level would allow
decompression of the RA and RV, alleviating s/s
of right heart failure.
 Considered after short term failure of maximal
medical therapy.
 Heart / Lung Transplantation

 1 year survival of 70%

 5 year survival of 50%
International Society for Heart and Lung Transplantation
Registry

 Effective therapy for patients with end

stage pulmonary vascular disease.
 Prognosis
 Survival at 1 year 63%
 Survival at 2 years 45%
 Improves to 87% survival at 2 years with
targeted therapy
 Mean age at diagnosis 34 years
 Mode of death: Most from Right Vent
failure

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 THANK YOU

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