Diseases of Pulmonary Circulation Flashcards
Describe fetal circulation
High pulmonary vascular resistance • Low oxygen tension • Low vasodilators (PgI2, NO) • High vasoconstrictors 8% of blood flow to lungs o Foramen ovale and ductus arteriosus shunt blood to systemic circulation
After birth = decreased vascular resistance
• Alveolar oxygenation
• NO
• PgI2
Persistent Pulmonary HT of the Newborn (PPHN)
• Failure of pulmonary vascular resistance to fall after birth
• Significant morbidity and mortality
• Respiratory distress and hypoxemia
Associated with:
• Maternal use of tobacco, ASA/NSAID’s, SSRIs
• Meconium aspiration or pneumonia
• Congenital anomalies
Normal pressures in pulmonary system
o RA: 0-7 (mmHg)
o RV: 15-25/3-12
o Pulmonary artery
• Systolic: 15-25
• Diastolic: 8-15
• Mean: 10-20
o PAOP: 8-12
• Systemic pressures: 120/80 (Mean = 95)
Explain the relationship between flow, pressure, and resistance in the pulmonary vascular bed.
PVR = [(PAP-LAP)/CO] x 80
o Multiply by 80 to convert to dyn sec/cm^5
PVR = dependent on pressures and flow
o Decreases with rising CO = due to recruitment and distension of capillaries → high capacitance of pulmonary system
o Is only 1/10th of systemic vascular resistance
Humoral mediators of pulmonary pressure Vasoconstrictors: • Endothelin-1 • Thromboxane A2 • Serotonin • Angiotensin II
Vasodilators • Nitric oxide • Prostaglandin I2 and E1 • Oxygen • Vasoactive Intestinal Peptide (VIP)
Define the values for Pulmonary HT
• Pulmonary HT = mean PA pressure > 25 mmHg at rest
Identify the broad categories of disease that may result in pulmonary hypertension as reflected in the WHO Classification scheme.
o Pulmonary arterial HT (PAH)
• Includes Idiopathic Pulmonary Arterial HT
o Pulmonary HT owing to left heart disease
o Pulmonary HT owing to lung diseases and/or hypoxia
o Chronic thromboembolic pulmonary HT
o Pulmonary HT with unclear multifactorial causes
Idiopathic Pulmonary Arterial HT
Idiopathic Pulmonary Arterial HT
• 1-2 cases/million people (rare)
• 2x common in females
• No ethnic predispositions
• Advanced nonspecific vascular changes of chronic HT (including plexiform lesions)
• Elevated BP in pulmonary arteries that can reach systemic values
• Familial cases due to mutation in Bone Morphogenetic Protein Receptor II gene (BMPRII)
o Autosomal dominant inheritance
o GF receptor for cell signaling with proliferation and apoptosis
Pathology of pulmonary HT
o Obstruction of small pulmonary arteries
o Intimal fibrosis
o Medial hypertrophy
o +/- Thrombotic lesion
o +/- Plexiform lesions (capillaries form a network spanning lumens of dilated thin walled, small arteries and may extend outside the vessel)
Clinical symptoms and exam findings of pulmonary HT
Early: nonspecific
• Dyspnea (1st symptom in 60%)
• Fatigue, chest pain, palpitations, syncope
Late: evidence of right heart failure
o Labs = nonspecific
o Chest x-ray: enlarged PA’s and RA/RV dilation
o PFT: reduced DLCO
Explain the concept of hypoxic pulmonary vasoconstriction and its adaptive importance.
- Vasoconstriction controlled by alveolar (not arterial) hypoxia
- Alveolar hypoxia: paO2 <60 mmHg
• Action occurs at smooth muscle cells in small Pulmonary arteries
o Hypoxia inhibits K+ channels → depolarization
• Inhibited proportionally to severity of hypoxia
o Voltage-gated Ca2+ channels = Ca2+ enters smooth muscle cells
o Increased cytosolic Ca2+ → myosin light chain phosphorylation → smooth muscle contraction
o Blood is shunted to area of better oxygenation
• Compare to systemic circulation = hypoxemia causes dilation
Describe the physiology and causes behind Eisenmenger syndrome.
Pulmonary vascular disease from long-standing systemic to pulmonic shunt
o Early stage: left to right shunting of blood due to higher systemic pressures
o Over time: increased flow in pulmonary arteries → changes resulting in increased pulmonary vascular resistance
o Reversal of flow with right to left shunted of blood
Dyspnea, marked cyanosis, clubbing pulmonary HT
Causes:
o Atrial shunts (ASD, Total/partial anomalous pulmonary venous return)
o Ventricular shunts (VSD, transposition of great vessels)
o Aortic shunts (PDA, truncus arteriosus)
Treatment = same for idiopathic pulmonary HT
Describe cor pulmonale.
• Right heart failure pathogenically related to pulmonary disorders/dysfunction
• Causes: (anything leading to hypoxemia or hypoventilation)
Lung disease:
• COPD, CF, IPF
Neuromuscular disease (chronic hypoventilation)
• ALS, myasthenia gravis, muscular dystrophy
Thoracic cage deformities
• Kyphoscholiosis
Disorders of ventilatory control
• Sleep apnea syndromes
Pulmonary vascular disease
Etiology:
o Low O2 levels → vasoconstriction → increased BP in pulmonary arteries
o Long standing strain on right heart
• Symptoms:
o Right-sided cardiac hypertrophy or failure and pulmonary HT
o Chest pain, SOB, fluid retention
• Treatment
o Underlying disease
o Oxygen and diuretics
• Prognosis:
o Increases mortality in COPD 2x
o Poor prognostic indicator for lung fibrosis patients
Describe the epidemiology of pulmonary thromboembolic disease.
- Common especially in hospitalized patients
- > 90% originate from deep-vein thrombosis
- Only about 10% of emboli cause infarction (Occurs when circulation is already inadequate)
- Distinguish pulmonary embolism from post-mortem clot by presence of lines of Zahn
Describe the effects of pulmonary embolism on gas exchange.
Hypoxemia • V/Q mismatch and shunt • 10-20% without hypoxemia • Up to 10% normal P(A-a)O2 gradient Hyperventilation → hypocarbia Increased dead space due to non-perfused areas of lung (increases V/Q) • Increased (a-A) CO2 gradient • Increased VD/VT • If severe → hypercarbia
Describe the effects of pulmonary embolism on hemodynamics
Reduction in cross-sectional area of vascular bed
• High pulmonary capacitance
• Can tolerate 30-50% occlusion before increases pulmonary artery pressure
Occlusion >75% of pulmonary vascular bed → RV failure (right heart can’t pump against high resistance)
Explain what happens to clots after they become lodged in the pulmonary vascular bed.
- Massive pulmonary embolism → obstructive shock, acute HF, death
- Need emergency therapy: embolectomy, fibrinolysis
