Pulmonary Circulation: Physiology and Pathology Flashcards
Fetal Pulmonary Circulation
Very high pulmonary vascular resistance
Low oxygen tension
Low vasodilators (PgI2, NO)
High vasoconstrictors
8% of blood flow to lungs
Foramen ovale and ductus arteriosus shunt blood to systemic circulation
Hypoxic Pulmonary Vasoconstriction
Alveolar hypoxia (not arterial) controls vasoconstriction
Action is at smooth muscle cell in small PA’s
Hypoxia inhibits potassium channels on smooth muscle cell membrane → depolarization
Voltage-gated Ca+2 channels allow Ca+2 to enter smooth muscle cells
Increased cytosolic Ca+2 leads to myosin light chain phosphorylation and smooth muscle contraction
Inhibition of potassium current proportional to severity of hypoxia
postnatal pulmonary circulation
After birth marked reduction in vascular resistance
Alveolar oxygenation ! NO, PgI2
Pulmonary Vascular Resistance
PVR = (mPAP-LAP)/CO (Woods units; normal <1.5)
PVR = (mPAP-LAP)/CO x 80 (dynes·sec·cm-5; normal 20-120)
- PVR is dependent on pressures and flow
- PVR actually decreases with rising CO due to recruitment & distension of capillaries allowing for high capacitance of pulmonary system
- PVR is only 1/10 of systemic vascular resistance (800-1200 dynes·sec·cm-5)
Diagnostic Evaluation of PH
- ECHO: primary screening test for PH
- Estimated PASP >35 mmHg, LA/RA dilation, tricuspid regurgitation, RV hypertrophy and dysfunction
- Evaluate for cause of PH
- Group 1: LFTs, ANA, HIV
- Group 2: left heart/valve disease (ECHO)
- Group 3: PFTs, overnight oximetry or polysomnogram
- Group 4: VQ scan
- Right heart catheterization: confirmatory test for PH
-
Diagnostic
- Right Heart Cath:
- mPAP > 25mmHg
- For PAH:
- PAOP < 15 mmHg
- PVR > 3 Woods units
- Right Heart Cath:
Mechanism of PH due to Left Heart Disease
Causes of Pulmonary Hypertension
- Idiopathic Pulmonary Arterial Hypertension
- Intimal, medial, and adventitial thickening of muscular pulmonary arteries (A) • Pulmonary arteritis • Concentric “onion skinning” artery thickening • Plexiform lesions (G)
- Left Heart Disease
- Systolic heart failure • Diastolic heart failure • Valvular disease • Congenital anomalies of the left ventricular outflow tract
- Chronic Thromboembolic Disease
Causes of Pulmonary Hypertension: WHO Classifications
Cor Pulmonale: overview
- RV failure that develops from chronic pulmonary hypertension from pulmonary disorders
- Primary pulmonary vascular problem (ie IPAH)
- Primary pulmonary airway/alveolar/parenchymal problem (ie COPD, pulmonary fibrosis)
- Does not include RV failure secondary to LV failure
- Evidence of altered structure (hypertrophy/dilation) and impaired RV function
Why does the right heart fail?
Right Ventricle
- Low pressure system: 20/10
- Right ventricle has thin muscle wall
- Not as adaptable to higher strain
Left Ventricle
- High pressure system: 120/80
- Left ventricle has thick muscle wall
- More adaptable to higher strain
Idiopathic Pulmonary Arterial Hypertension
- ** diagnosis of exclusion **
- 1-2 cases per million in general population
- 3-4x as common in females
- 3rd-5th decades
- No ethnic predispositions
- Hereditary factors
- Elevated blood pressure in pulmonary arteries that can reach systemic values
Normal Pulmonary Vascular Response to Hyperdynamic State
- PAP rises due to CO (flow)
- mPAP = PVR x CO + LAP
- Decrease in PVR due to recruitment and vascular distention
Lung Disease
- Destruction of lung parenchyma leading to loss of vascular bed
- Stiffening of large PAs
- Chronic hypoxia leads to medial hypertrophy and musculariza/on of small PAs
- Chronic inflamma/on intensifies vascular remodeling
Pulmonary Hypertension
Definition:
- Mean PAP > 25 mmHg at rest
High morbidity/mortality from right heart failure
Presenting symptoms
- Dyspnea in majority
- Syncope, chest pain, edema
Many potential etiologies
Pulmonary Vasodilators
- Alkalosis
- Hyperventilation
- Oxygen
- Nitric oxide (Produced by endothelium; Can be delivered exogenously (inhaled)
Pulmonary Hypertension in Lung Disease and Hypoxia
- Second most common cause of PH
- Typically only in severe disease (think hypoxia, acidosis, hypercarbia)
- Interstitial lung disease (ie pulmonary fibrosis, sarcoid)
- COPD/Emphysema
- Sleep disordered breathing (ie obstructive sleep apnea, obesity hypoventilation syndrome)
- Treatment aimed at underlying disease, avoiding vasoconstrictors ie hypoxia
mediators of pulmonary vasoconstriction
Hypoxia • Acidosis • Hypoventilation • Hypercarbia
Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
- Loss of vascular surface area due to clot
- More common with large clot burden or recurrent PE
- Microvascular remodeling similar to that seen in PAH
- Occurs in up to 4% of PE, typically within 2 yrs of PE
- 1 in 4 patients with CTEPH have NO prior history of PE
- Requires lifelong anticoagulation
- Should be evaluated for surgical embolectomy
Pulmonary Hypertention in Left Heart Disease
Most common cause of PH
- Common: systolic or diastolic heart failure, aortic or mitral valve disease
- Uncommon: Restrictive pericarditis, infiltrative cardiomyopathy
- True incidence unknown, but may affect up to 50% of patients with left heart failure
Differentiated from PAH by elevated left atrial pressure (and therefore PAOP)
Treatment aimed at treating left heart disease
Treatment of PAH
Humoral Mediators of Pulmonary Pressure
Vasoconstrictors
- Endothelin-1
- Thromboxane A2
- Serotonin
- Angiotensin II
Vasodilators
- Prostaglandin I2 and E2
- Oxygen
- Vasoactive Intestinal Peptide (VIP)
Cor Pulmonale: common causes, symptoms, findings and things it can cause
- Most common causes: COPD, pulmonary fibrosis
- Symptoms: Progressive dyspnea, syncope, chest pain
- Exam findings: Elevated JVP, loud S2, holosystolic murmur at the left lower sternal border, hepatomegaly, ascites, lower extremity edema
- Common cause of hospitalization and death
Clinical Presentation of PH
- Early - nonspecific symptoms
- Dyspnea is initial symptom in 60%
- Fatigue, chest pain, palpitations, syncope
- Late – evidence of right heart failure
- Labs nonspecific, elevated BNP common
- CXR – enlarged PA’s and RA/RV dilatation
- PFT’s – reduced DLCO