Transcript Diseases of the Pulmonary Circulation

Diseases of the Pulmonary
Circulation
J.B. Handler, M.D.
University of New England
Physician Assistant Program
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Abbreviations
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PE- pulmonary embolus
DVT- deep vein
thrombophlebitis
CO- cardiac output
HF- heart failure
OCP- oral contraceptive pill
PAP- pulmonary artery pressure
V/Q- ventilation/perfusion
CVP- central venous pressure
RR- respiratory rate
P2- pulmonic valve component
of the 2nd heart sound (S2)
Vit-vitamin
Dx- diagnosis
INR- international normalized
ratio
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S4- abnormal 4th heart sound
NSST-T- non specific ST-T
wave changes
ST- sinus tachycardia
ABG- arterial blood gas
PuVR- pulmonary vascular
resistance
PPH- primary pulmonary
hypertension
RAE- right atrial enlargement
RVE- right ventricular
enlargement
S2- second heart sound
Rx- treatment
PTT- partial thromboplastin
time
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Pulmonary Thromboembolism
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Embolization of thrombus from the venous system
into the pulmonary arterial circulation; common,
serious and life threatening
200,000 annual mortality in USA
– 3rd leading cause of in-hospital deaths
– Majority of deaths from PE unrecognized until postmortem
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5-7% mortality rate of diagnosed cases with a 4050% mortality rate of undiagnosed cases
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Pulmonary Embolism
The presence of DVT should always
sound an alarm. Prior DVT or PE carry a
substantial risk for subsequent PE.
 Symptoms: Often very difficult to
recognize as symptoms are not specific to
PE.
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– 97% of patients with PE will have at least one
of the following: tachypnea, dyspnea,
pleuritic chest pain (infers infarction). About
1/3 of patients will have tachycardia.
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DVT
Images.google.com
Pulmonary Thromboembolism
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DVT is the most common site of development of
thrombus. Usually popliteal and/or iliofemoral
vein involvement with subsequent embolization
(50-60%) to the pulmonary circulation.
Calf involvement alone carries much less risk of
significant embolism.
– Calf vein propagation to popliteal and iliofemoral veins
occurs in 20% of patients with initial calf involvement.
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Pelvic vein thrombosis also common source.
50% cases of PE lack characteristic symptoms;
essential to have high index of suspicion.
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Risk Factors for DVT
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Venous stasis: Immobility, post-op (large
operations, orthopedic procedures), post stroke.
Increased CVP: Decreased CO, CHF, pregnancy.
Hypercoagulability: Meds (OCP), diseases
(malignancy), and inherited- several forms:
– Factor V Leiden: A hereditary hypercoagulability
disorder; common (3% heterozygous incidence) in
healthy adults. 20-30% of patients with DVT have this
disorder.
– Factor V Leiden: Modified clotting factor V, resists
degradation by activated Protein Ccoagulation.
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Intracardiac Pressures
4-12
4-12
4-12
4-12
4-12
4-12
Images.google.com
Pathophysiology
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Obstruction to pulmonary vascular bed by
thrombus.
Vasoconstriction develops in the pulmonary
arteriolar bed (PuVR) as a result of:
– Neurohumoral reflexes, hypoxia, and tissue injury
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Result is PAP.
 PAPRt heart strain  CO (RVH if PAP
s over time)  RV failure: Cor Pulmonale.
Impaired gas exchange: alveolar dead space
from vascular obstruction.
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Pathophysiology
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physiologic dead space, CO, hypoxemia and
surfactant depletion result in atelectasis.
– Atelectasis contributes to shunting (below).
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Right to left shunting plays a small role:
– Atelectasis.
– Large PE: Redirection of blood flow into “normal” lung
but if inadequate alveolar reserveshunting.
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Loss of surfactant, edema and hemorrhage lead to
decreased pulmonary compliance, work of
breathing.
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Ventilation/Perfusion
Images.google.com
Symptoms
Dependent on number/size of the emboli
and pre-existing pulmonary status.
 Constellation of findings: dyspnea,
pleuritic (inspiratory) chest pain and
tachypnea are predominant
symptoms/signs; others include palpitations,
wheezing and hemoptysis.
 Note: must have high index of suspicion in
order to make Dx in many patients.
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Signs
Signs: Increased RR, tachycardia, crackles,
S4 gallop, decreased S2 splitting with
increased P2; friction rubs and cyanosis less
common.
 Clinical findings of DVT present in only
30-40% of patients with PE but 60-70% will
have evidence of DVT by non-invasive
imaging (see below).
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Investigational Findings
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ECG changes common: ST, NSST-T changes.
ABG: Respiratory alkalosis, decreased PO2.
Plasma D-dimer: (>300-500ng/ml) a degradation
product of cross-linked fibrin- usually elevated
in presence of thrombus (97% sensitivity), but
not specific (45%). Commonly combined with
other diagnostic studies (CT
angiography)predicts likelihood of PE.
CxR: often abnormal- atelectasis, pleural
effusions, pleural based infiltrates; necessary to
exclude other pulmonary pathology.
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Images.google.com
V/Q Lung Scan
Radioisotopes used to image ventilation and
perfusion. Defects develop in areas of lung
that remain ventilated without perfusion;
inaccurate in presence of other pulmonary
pathology.
 Graded low (normal), intermediate and high
probability for PE.
 Supplanted as diagnostic test by Helical CT
angiography (below).
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Pulmonary Circulation Imaging
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Helical (spiral) CT Angiography: Sensitive for
proximal vessel thromboembolism; overall 83%
sensitive, >90% specific; alternative to V/Q
scanning as a screening procedure. More often
done compared to V/Q.
Pulmonary angiography: reference standard for
the Dx of PE- Invasive with 5% complication rate
(contrast reaction, renal failure, arrhythmias) high
sensitivity, specifity. Indicated when V/Q or CT
scans are indeterminate, DVT studies are negative,
and PE still suspected clinically.
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Helical CT: Pulmonary Embolus
Pulmonary Angiography
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DVT Studies
If Dx is uncertain and DVT is proven, likely
that PE is present if clinically suspected.
 Venous ultrasound with doppler: Noninvasive test of choice for DVT.
 Contrast Venography: “reference standard”highly accurate and invasive, has been
replaced by ultrasound which is noninvasive and easier to perform.
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Integrated Approach for Dx of PE:
Clinical Features + Diagnostic Testing
Clinical feature
Points
Clinical symptoms of DVT
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Other diagnosis less likely than
PE
Heart rate greater than 100 beats
per minute
Immobilization or surgery within
past 4 weeks
Previous DVT or PE
3
1.5
Clinical Probability of PE
Score
PE likely
>4
PE unlikely
4
1.5
1.5
Hemoptysis
1
Malignancy
1
Total points
Wells et. al
Clinical Probability of PE
PE Unlikely
PE Likely
D-dimer assay
Helical CT-PA
Negative
Positive
PE Excluded
PE excluded
- study
Current fig 9-1
Normal
Findings of PE
Rx for PE
Indeterminate
LE US or Pulm angiogram
+ study
Treatment of 1st PE
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Full anticoagulation for minimum 6 months or
longer depending on risk factors for recurrence.
Unfractionated heparin: Binds to and potentiates
antithrombin III inactivates clotting factors
IXa, Xa, XIa, XIIa; retards additional thrombus
formation.
Administered by continuous IV infusion and
requires frequent monitoring (highly protein
bound) of PTT for dose adjustment; for 5-7 days.
Wt. Based dosing: 80U/kg loading dose, then
18U/kg/hrgoal PTT 1.5-2.5x control (46-70 sec)
Risks: Bleeding, thrombocytopenia.
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Low Molecular Weight Heparin: depolymerized
heparin, less protein and cellular bound, increased
bioavailability; also given for 7 days. More
predictive dose response, as/more effective than
unfractionated heparin. Decreased risk of
hemorrhage and thrombocytopenia; 1-2x daily
dosing (weight based) without need for lab testing.
Warfarin- oral anticoagulant, blocks action of
Vit K, inhibiting hepatic synthesis of Vit K
dependent clotting factors (II, VII, IX, X).
Initiated over 5-7 days (with patient on heparin)
and continued for desired period of time. Goal:
INR (adjusted PT) of 2-3.
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Thrombolytic Therapy
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Streptokinase, Urokinase and t-PA: directly lyse
intravascular thrombi and accelerate resolution of
emboli within 1st 24 hours compared to standard
heparin therapy, but do not decrease mortality.
Indications: patients with massive PE at high
risk of death (unstable on heparin).
Contraindications: active internal bleeding, stroke
in prior two months, surgery or trauma in prior 6
weeks and uncontrolled hypertension.
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Surgical Interventions
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Mechanical or surgical thrombus extraction- last
resort in a dying patient.
Vena caval interruption: Indicated in patients with
DVT/PE that cannot be anticoagulated or recurrent
PE while already fully anticoagulated. Vena caval
filter/umbrella can be introduced percutaneously
via internal jugular vein.
Prognosis of PE if diagnosed: < 3% incidence of
death from recurrent PE if initial event is
recognized and adequately treated.
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Prevention of PE
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Identify patients at high risk for DVT: lengthy
hospitalization/immobilization, orthopedic
surgery, esp. hip repair (incidence of DVT 1020% if untreated with prophylactic anticoagulation
and other measures).
Strategies for prevention:
-early ambulation
-elastic stockings
-mechanical compression devices
-anticoagulation.
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Pharmacologic Prophylaxis
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Patients with high risk for DVT and PE
Low doses (below full anticoagulation dose) of
anticoagulants (’s risk of bleeding) decreases
incidence of DVT/PE:
Unfractionated Heparin
Low molecular weight (LMW) heparin
Sometimes continued as OP (warfarin/coumadin)
in patient likely to remain immobile.
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Pulmonary Hypertension
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Pulmonary circulation is a low pressure system
with high blood flow and low PuVR (200
resistance units compared with 800-1000 RU for
the systemic circulation.
In a variety of disease states (e.g. PE) there is
constriction of smooth muscle in the walls of
pulmonary arteriolar resistance vessels.
Pulmonary Hypertension is present when the PAP
rises to a high level, inappropriate for a given level
of cardiac output.
PPH- rare idiopathic disorder in woman.
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Idiopathic (Primary) Pulmonary
Hypertension
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No other underlying cardiopulmonary disease: An
arteriopathy. Medial hypertrophy, fibrosis and
recanalized thrombi are common pathology
findings; poor prognosis- mean survival post Dx is
2-5 years.
Marked PuVR and PAP.
Association: anorexigens, collagen-vascular
disease.
– Fenflouramine appetite suppressants: Marked recent
in PPH (U.S. and Europe); similar events in 1960’s
with Amrinox. Both taken off market.
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Secondary Pulmonary HTN
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Reduction of x-sectional area of the pulmonary
vascular bed:
– Vasoconstriction: Hypoxia from any cause (most
important and potent stimulus), lactic acidosis.
– Loss of vessels: Vasculitis, emphysema, interstitial dis.
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Obstruction of vessels: Multiple or recurrent PE.
Chronically increased pulmonary venous pressure
(HF, mitral stenosis).
pulmonary blood flow: Congenital Ht Disease.
Once present, secondary structural changes occur
resulting in further destruction of vessels.
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Signs and Symptoms
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Dyspnea- initially exertional, then rest.
Retrosternal chest pain (mimics angina); fatigue
and syncope result from decreased CO.
Physical Exam: Narrowly split or single S2, P2.
CxR: Dilated main PA with “pruning” of vessels.
Echo-Doppler: best non-invasive tool: RAE, RVE;
elevated PA and RV systolic pressure.
Right heart cath: precise measurement of right
heart pressures essential to Dx and Rx.
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Treatment
Treat underlying disease process if present.
 Supplemental chronic O2 if hypoxemic.
 Full anticoagulation: PPH only
 Prostacyline (Epoprostenol, Treprostinil):
via continuous IV infusion potent
pulmonary vasodilator; symptoms and
mortality.
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Treatment
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Bosentan (Tracleer): new oral endothelin-1
receptor antagonist for chronic PAH; symptoms.
Sildenafil: inhibits phosphodiesterase type 5;
pulmonary vasodilator- improves symptoms.
Lung or heart/lung transplant: 50-65% 2 year
survival. Better long term survival with bilateral
(vs. unilateral) lung transplant.
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