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Ohm's Law
 - As resistance goes up:
- 1. Pressure increases (pulmonary HTN)
- 2. CO decreases
- *usually both
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Pulmonary Arterial Hypertension
Mean pulmonary arterial pressure > 25mmHg
- Often estimated by Echo:
- -measures tricuspid regurgitation jet (present in most ppl)
- -systolic PAP = (4V2) + CVP
- Measure with Right Heart Cath:
- -need accurate number
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Presentation
- -female predominance (especially idiopathic)
- -may develop at any age (related to etiology)
- Symptoms:
- -SOB
- -hypoxemia
- -swollen feet and ankles
- -chest pain
- -syncope
- -cyanosis
- Physical Exam Findings:
- -hypoxemia (usually later in course)
- -elevated JVP
- -enhanced/delayed P2 (pathologic splitting)
- -Right sided S3 or S4 gallop
- -pulmonic bruit (CTPH)
- -peripheral edema
- -possibly clubbing
- Imaging:
 - -enlarged cardiac silhouette (esp RA)
- -enlarged R pulmonary artery
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Types of PAH
- 1. PAH
- -idiopathic
- -Heritable
- -Drug induced
1'. Pulmonary veno occlusive disease/Pulmonary capillary hemangiomatosis
2. Pulmonary HTN due to left heart disease
- 3. Pulmonary HTN due to lung diseases/hypoxia
- -COPD
- -interstitial lung disease
- -sleep-disordered breathing
- -high altitude
4. Chronic thromboembolic pulmonary hypertension
- 5. PH with unclear or multifactorial mechanisms
- -hematologic disorders
- -systemic disorders
- -metabolic disorders
- -other
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Familial PAH
- Bone Morphogenetic Protein Receptor 2 (BMPR2)
- -70% of familial cases
- -20% of idiopathic
- Activin-like kinase type 1 (ALK1)
- -found in HHT (hereditary hemorrhagic telangectasia)
- Endoglin (ENG)
- -also found in HHT
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Drug-Induced PAH
- 1. Anorexic Agents
- -fen-phen
2. Methamphetamine
3. Cocaine
4. SSRIs? MDMA?
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HIV-Associated PAH
- -attributed to viral effect itself
- -may be more closely related to other lifestyle choices (amphetamines)
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Autoimmune-Associated PAH
- -primarily seen with systemic sclerosis (scleroderma)
- -may be severe and rapidly progressive
- -patients benefit from immunosuppression (cyclophosphamide, prednisone)
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Portopulmonary Hypertension
- -PAH associated with elevated portal venous pressures
- -typically due to cirrhosis
- -high mortality if untreated (still poor with tx)
- -usually treatable with PAH meds
- -high risk of mortality with liver transplant
NOT THE SAME AS HEPATOPULMONARY SYNDROME
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Systemic-to-Pulmonary Shunts
1. Congenital abnormalities (VSD, ASD, PDA)
- 2. Eisenmenger's syndrome
- -L to R shunt becomes R to L shunt
Patients are often very sick
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Pulmonary veno occlusive disease (PVOD)/ Pulmonary Capillary Hemangiomatosis (PCH)
- -HTN on arterial side secondary to HTN on venous side
- ** meds to tx PAH usually make them worse!
- Imaging:
 - -nodules
- -well demarcated lymphatics within pulmonary parenchyma
- -lymph adenopathy
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Pulmonary Hypertension due to left heart disease
- 1. LVF (most common cause of elevated pulmonary artery pressure)
- 2. Mitral Valve stenosis
- 3. Mitral Regurg
- 4. Restrictive cardiomyopathy
- 5. Aortic valve stenosis
NOT cor pulmonale (lungs are not the initial insult)
- Do not typically improve with standard PAH therapy
- -increased blood flow into LA overloads the L heart --> pulmonary edema, effusions, respiratory failure
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Neurohormonal Reflex
 - -increased LA stretch triggers vasoconstriction of pulmonary arterioles
-protects capillaries from high pressure
-can be overwhelmed (pulmonary edema, capillary rupture/hemorrhage, pleural effusions)
-P in PA increases much more than LA pressure
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Pulmonary Hypertension due to lung disease and/or hypoxia
- Causes:
- -COPD
- -Interstitial lung disease
- -Sleep-disordered breathing
- -Chronic high altitude exposure
- -Developmental abnormalities
- Chronic Hypoxemia:
- -leads to hypoxic vasoconstriction (may develop SM proliferative changes)
- Parenchymal Destruction:
- -lose pulmonary vasculature --> same amount of blood/fewer vessels --> increased resistance
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Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
- Accumulate multiple emboli over time
- -can result from recognized acute PE (estimated in 2-4% of PE)
- May have a genetic predisposition
- -mutations in fibrinogen
- Treatment:
- -may respond to traditional PAH meds
- -Surgical resection the mainstay of therapy (Pulmonary thromboendarterectomy)
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PH with unclear or multifactorial mechanisms
- 1. Hematologic disorders
- -myeloproliferative disorders
- -splenectomy
- 2. Systemic disorders
- -sarcoidosis
- -pulmonary Langerhans cell histiocytosis
- -NF
- -vasculitis
- 3. Metabolic disorders
- -glucogen storage disease
- -gaucher disease
- -thyroid disorders
- 4. Other
- -tumor obstruction
- -fibrosing mediastinitis
- -chronic renal failure
- Treatment:
- -very difficult to treat
- -not usually responsive to PAH meds
- -address underlying cause if able
- -manage symptomatically
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PAH Pathology
-SM hypertrophy of small arteries and arterioles
-intimal hyperplasia (luminal obliteration)
-plexiform (weblike) changes of small arterioles
-RV concentric hypertrophy, dilation
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PAH Morbidity and Mortality
- -Untreated 50% survival at 2 years
- -Still poor even with therapy
- -Frequent hospitalizations
- -repeated surgical procedures (catheter placement)
- -electrolyte abnormalities
- -renal dysfunction
- -bloodstream infections (catheters)
- -liver dysfunction
- -limited exercise tolerance
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Classes
I: no functional limitations
II: sx with moderate exertion
III: sx with mild exertion
IV: sx at rest
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Medical Therapy
- 1. CCB
- -verapamil
- -diltiazem
2. PDE5 inhibitors
3. Endothelin receptor antagonists
4. Prostacyclins
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Calcium Channel Blockers
-ineffective in most patients (class I)
-inhaled NO testing during R heart cath to test for vasoresponsiveness
-patients typically graduate to more effective therapies
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PDE5 Inhibitors
-good oral therapy for mild disease (I or II)
-typically well tolerated
-not used first line for class III to IV
-often started by non-specialists --> may delay necessary evaluation and tx
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Endothelin Receptor Antagonists
- -more potent than other oral agents
- -can be used in mild-moderate (class II-III)
-must monitor hepatic function but typically well tolerated
-HIGHLY TERATOGENIC
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Prostacyclins
- -Epoprostenol
- -Treprostinil (inhaled)
- -Iloprost (inhaled)
- -most potent class of medications (Class III-IV)
- -prolong survival and improve quality of life
-difficult administration: continuous IV infusion (need indwelling catheter)
-drug delivery associated complications (infections, surgery)
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Natural Course: drop in PA pressure
- -remember Ohm's law!
- -Drop in PA pressure may be due to decreased PVR OR decreased cardiac output!
- -patients may actually be getting WORSE!
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Transplantation
-reserved for severe progression despite medical therapy
-typically bilateral (now starting to do more unilateral)
- High risk associated with surgery/anesthesia
- -increased intrathoracic pressure from mechanical ventilator leads to increased RV pressure --> right heart failure
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