9/23- Pulmonary Vascular Diseases Flashcards
What are the systolic/diastolic/mean BP for pulmonary arteries?
Characteristics of pulmonary circulation?
Pulmonary circulation is high flow, low pressure, highly compliant system (low resistance)
- Systolic: 30 mmHg
- Diastolic: 10 mmHg
- Mean: 15 mmHg
What regulates vascular tone in pulmonary circulature?
Vascular endothelium
- NO (dilator)
- Endothelin (constrictor)
Autonomic nervous system
- a1 adrenergic receps (constriction)
- B2 adrenergic receps (dilation)
What is the mechanism of NO dilation of vasculature?
- Secreted by endothelial cells
- Activates guanylate cyclase (GC) to increase cGMP levels
- Also activates Ca dependent K channels in vascular smooth muscle
- Dilates both venous > arterial
- NO is a gas, which can be inhaled to result in primary pulmonary vasodilation
What are the determinants of pulmonary artery pressure?
- Blood volume
- Rate of fluid flow through system (CO, viscosity, vessel size)
- Pressure inhibiting flow across cap bed (left atrial pressure)
- PAP = CO x (PVRa + PVRcaps + PVRv)
What are some pulmonary vascular disorders?
- Pulmonary hypertension
- Pulmonary embolism
- Pulmonary vasculitides
- Pulmonary arteriovenous malformation
What is the cutoff for pulmonary HTN?
Mean PA pressure > 25 mmHg
(recall, normal is 15 mmHg)
How is Pulmonary HTN classified?
1. Pulmonary arterial hypertension (PAH)
- Toxin/drug use
- HIV
- Portal hypertension, liver cirrhosis
- Sickle Cell Disease
- Group 1 disease have specific targeted treatments*
2. Left heart disease
3. Lung diseases and/or hypoxia
- Obstructive
- Restrictive
- Chronic hypoxemia
4. Chronic thromboembolic pulmonary HTN (CTEPH)
- Persistent elevation of pulmonary P -> symptoms and heart failure
5. Unclear multifactorial mechanisms
- Sarcoidosis
What are the structural and functional changes in pulmonary HTN?
Increased PVR
- Sustained vasoconstriction (muscle layer hypertrophy and permeation into other layers)
- Vascular remodeling
- In-situ thrombosis
- Increased arterial wall stiffness
What is idiopathic Pulmonary Arterial HTN?
- Epidemiology
- Pathology
Epidemiology
- Uncommon
- More in women
- Mean age = 50 yo
Pathology
- Hypertrophy/fibrosis vascular bed
- In situ thrombosis
What is the prognosis for idiopathic Pulmonary Arterial HTN?
- Variable
- Mean survival 2-3 yrs from time of diagnosis
- Depends on severity, cardiac function, exercise tolerance, response to vasodilators
- Non-responders: 9-18 months
- Responders w/ preserved function:- >50% for 5 yrs
What are the clinical features of PAH?
- Shortness of breath
- Atypical chest pain
- Palpitations
- Cough
- Syncope (if advanced; developing RHF)
- Hemoptysis
- Hypotension
- Tachycardia
- Atrial arrhythmias
- Loud P2
- Tricuspid regurgitation murmur
- JVD
- Signs and symptoms of cor pulmonale (RHF)
Case)
- 45 yo female with worsening SOB
- Chest pain, orthopnea, PND What is seen on her CXR?
- Don’t see infiltrate, pneumonia, fibrosis
- Preserved lung structure/anatomy
Heart seems somewhat abnormal:
- Large pulmonary artery indicative of pulmonary HTN
What is seen of echocardiogram of pulmonary HTN?
- Small LV cavity; normal LV ejection fraction
- Severe RV dilatation, severely reduced RV global systolic function
- PA systolic pressure estimate 105-110 mmHg
- No interatrial septal defect
What does the evaluation of suspected pulmonary HTN look like?
- ECHO to screen for PH and r/o primary cardiac disease
- PFT to r/o primary lung disease (esp. COPD) and restrictive lung disease
- Spiral CT (possible angiogram) to r/o pulmonary vascular disease (thromboembolic disease, vasculitis)
- Right heart cath: Pulmonary artery pressure, PCWP, hemodynamics
What is the treatment for PAH (pulmonary HTN in general?) ?
- Optimize therapy for related diseases
- Supportive (O2, anticoagulation, diuretics, digoxin)
- Targeted therapy - Surgical
What are targeted therapies for PAH?
- Prostacyclins
- Endothelin receptor antagonist
- NO pathway drugs
- Soluble guanylate cyclase stimulators
What are characteristics of prostacyclins for PAH treatment?
Examples (probably don’t need to name)?
Vasodilatory, antiplatelet, antiproliferative
- Berapost (PO)
- Epoprostenol (IV)
- Iloprost (inhaled)
- Treprostinil (SQ, IV, inhaled, PO)
What are characteristics of endothelin receptor antagonists for PAH treatment?
Examples (probably don’t need to name)?
Blocks receptor for ET-1, a potent vasoconstrictor and mitogen
- Bosentan (PO)
- Ambrisentan (PO)
- Sitaxsentan
What are examples of NOs for PAH treatment (probably don’t need to name)?
- Phosphodiesterase inhibitors: Sildenafil/Tadalafil
- Inhaled NO
- Dipyridamole
Name soluble guanylate cyclase stimulators (probably don’t need to name)?
Riociguat
What are surgical therapies for PAH?
Lung transplantation
- Double lung transplantation typically
- Heart-lung if PAH secondary to congenital heart disorders
Atrial septostomy
- Reduces RVEDP, improves cardiac index at expense of decreased PaO2
- Bridge to transplantation
Pulmonary endarterectomy for CTEPH
What is cor pulmonale?
- Cause
- Signs
- RV hypertrophy (and ultimately resulting in right heart failure) 2ndary to increased PVR
- Most commonly results from chronic pulmonary diseases (esp. COPD) that affect pulmonary vasculature.
- Signs:
- Hepatojugular reflux
- Lower extremity edema
- Pulsatile liver
- Tricuspid regurgitation
- Ascites
What is the treatment for cor pulmonale?
- Treat underlying cause(COPD, etc.)
- Minimize vasoconstriction, vasodilate (O2),
- Improve cardiac output w/rhythm control and contraction
Epidemiology of PE/DVT?
- Venous thromboembolism is a major medical problem
- > 5 million DVT cases annually
- Of these, 650,000 develop pulmonary embolism (PE)
- Of pts with PE, 100,000 die annually
- Not uncommon cause of death in acute care hospital setting
- > 70% of pts that die of PE are not suspected before death; maintain a high index of suspicion and pursue the diagnosis when warranted
What are causes of pulmonary embolism?
- Thrombus
- Fat (occurs in long bone fractures)
- Tumors
- Trophoblast
- Air (catheter placement, scuba diving)
- Amniotic fluid
What is VIrchow’s triad?
- Venous stasis
- Intimal injury
- Altered coagulation
What are the risk factors for thrombosis?
- Age > 70 yo
- Obesity
- Sedentary/Bed rest
- Trauma
- Chronically ill
- Pelvic surgery/trauma
- Prolonged anesthesia (>1 hour)
- Surgery of lower extremities
- Hip fracture/replacement
- Pregnancy/postpartum
- Right ventricular failure
- Oral contraceptives (5-10 fold increase)
- Underlying malignancy (Trousseau’s syndrome)
- Inherited/acquired deficiency of naturally
- occurring anticoagulants:resistance to activated protein C (Factor V Leiden)
- Prothrombin gene mutation
- protein C deficiency
- protein S deficiency
- Antiphospholipid antibody syndrome
- Anti-thrombin III deficiency
- Hyperhomocysteinemia
What are symptoms of DVT?
- Pain
- Tenderness
- Swelling
- (+) Homan’s sign: dorsiflexion of foot/ankle -> pain
What are the symptoms and findings of pulmonary embolism?
Symptoms
- Dyspnea
- Impending doom
- Palpitations (tachycardia)
- Hemoptysis and pleuritic chest pain are signs of infarction (uncommon, 20% of patients with significant cardiopulmonary disease)
Findings
- Tachypnea
- Tachycardia
- Low grade fever
- With massive embolism
- fixed split of S2, and S3 or S4, dilated neck veins, and cyanosis, hypotension
What is the diagnostic process of DVT?
- Contrast venography: Gold standard, only accurate method in asymptomatic individuals.
- IPG: Serial negative IPG or US is comparable in accuracy to negative venography in patients with suspected DVT
- Compression ultrasonagraphy*: Often the diagnostic modality of choice. The sensitivity and specificity approach 97%-98% for symptomatic patients.
- MRI: High sensitivity and specificity, expensive
- D-dimer: Low levels of plasma D-dimer (under 500 ng/mL) by ELISA technique may have a high negative predictive value
T/F: You can get DVT in upper extremity veins?
True!
What is seen on CXR for someone with DVT?
- Localized oligemia -> Westermark sign:
- Hampton’s hump
- Consolidation (infarct)
- Usual report is “normal”
What is seen on EKG for someone with DVT?
- Tachycardia
- Right axis deviation (right sided strain)
- New onset atrial fib
What is S1Q3T3?
The classic finding; “not common, but always talked about”
What are the diagnostic tests on PE of someone with DVT?
ABG’s: increased A-a difference;
Pa02 may be above 80;
C02 usually decreased
Remember to calculate the A-a diff
- A-a difference is usually increased
- Alveolar gas equation
- [FIO2(PB-PH20) – PaC02/R] – Pa02
- [150-PaC02/0.8] - Pa02
What is the Wells Diagnostic Scoring? Considerations?
Predicts clinical likelihood of PE
- Signs/symptoms of DVT (3)
- Another diagnosis less likely than DVT (3)
- HR > 100 (1.5)
- Immobilization/surgery within 4 wks (1.5)
- Previous DVT/PE (1.5)
- Hemotpysis (1)
- Malignancy (active or treated within 6 mo) (1)
Pre test probability: ≤ 2 low; 2-6 Moderate; >6 High
What is the diagnostic approach?
- Chest CT with contrast, PE protocol
- Less commonly VQ scan
- Rarely, pulmonary angiogram
- If negative or inconclusive and clinical suspicion present….
–>further diagnostic testing
- Evaluate for DVT or perform other diagnostic test.
Pros/cons of diagnosing PE with helical/spiral CT?
Helical/spiral CT:
Advantages
- Specificity
- Availability
- Safety
- Relatively rapid
- Other diagnosis
- Advancing technology
Limitations:
- Expense
- Not portable
- Need contrast
- Poor visualization in some areas
- Contraindication: renal insufficiency/allergy
- Reader expertise
What is a ventilation perfusion scan (VQ scan)?
- Nuclear medicine test to evaluate ventilation (V) and perfusion (Q)
- “Matched” defects
- non-diagnostic, compare to x-ray
- “Unmatched” defects
- suggestive of perfusion abnormality
Describe Pulmonary Angiogram
- Process
- Purpose
- Commonality
- Intra-arterial dye
- Directly assesses vasculature
- Rarely used now
What do each of these gross pictures show?
1- Embolus with infarct
2- Saddle embolus
3- Infarct
How can DVT be prevented?
Based on level of risk and risk of bleeding
- Low: (under 10% VTE without prophylaxis) early ambulation only
- Moderate: (risk of VTE 40%): most general surgical pts or med pts at bedrest; give LMWH, LDUH, fondaparinux or mechanical if bleeding risk high
- High: orthopedic, major trauma, spinal cord injury; give LMWH, fondaparinux, rivoroxaban, Vit K antagonist; mechanical if bleeding risk high
How to treat PE?
Anticoagulation
- Acute
- Weight-adjusted heparin IV
- LMWH
- Long term
- Warfarin
- Oral factor XA inhibitors
- LMWH Thrombolysis
Embolectomy
IVC Filter
What is HIT?
- Mechanism
- Labs
Heparin Induced Thrombocytopenia
- Immune-mediated drug reaction
- Results in platelet removal -> thrombocytopenia (most common, 90%)
- Results in platelet aggregation and release of procoagulant microparticles (thrombosis)
- Defined by presence of heparin-reactive antibodies to platelet factor 4 (HIT Abs)
What are complications of HIT?
- Deep vein thrombosis
- Pulmonary embolism
- Myocardial infarction
- Occlusion of limb arteries (possibly resulting in amputation)
- Cerebrovascular accidents (stroke, TIA)
- Skin necrosis
- End-organ damage (e.g., adrenal, bowel, spleen, gallbladder or hepatic infarction; renal failure)
- Death
What is Warfarin?
- Mechanism
- Dynamics/activity
- Metabolism
- ASEs
- Management
- Reversal
- Antagonizes Vitamin K dependent factors (Factors 2, 7, 9, and 10 as well as protein C and protein S)
- Delayed effect based on the shortest 1/2 life (Factor 7: 6 hrs); 18-24 hrs
- Crosses placenta; CONTRAINDICATED in pregnancy
- Numerous drug-drug, drug-disease (liver), and drug-food (Vit K) interactions
- Careful monitoring of INR (standardized msmt of PT); usual targeted range is 2-3
- Reversal with Vitamin K (mild) or FFP
What things diminish Warfarin effect? INR level?
INR level will be low
- Inhibits drug absorption: Cholestyramine
- Increases metabolism (enhance p450): Barbiturates, Carbamazepine, Phenytoin, Rifampin
- Vitamin K: foods, esp leafy greens
What things enhance Warfarin effect? INR level?
INR will be high
- Displaces from albumin: choral hydrate
- Decreased metabolism (inhibits p450): Amiodarone, clopidogrel, ethanol, fluconazole, fluoxetine, metronidazole, sulfamethoxazole
- Eliminate gut bacteria and decrease K: Broad-spectrum antibiotics
What should the duration of therapy be for ?? (HIT?) (PE?)
- 3 months in patients with transient risk factors
- May be life long in patients with recurrent thrombosis or continued risk factors (e.g. malignancy, hypercoagulable state)
What is an IVC filter? What is it used to treat?
IVC filter: treatment of PE
- Patients with massive PE who could not tolerate a recurrence
- Patients with contraindications to anticoagulation
- Recommended for repeat PE despite anticoagulation or when anticoagulation is contraindicated
- Filter is a wire apparatus inserted through a catheter in the inferior vena cava to prevent PE
- Filter may be removed
What are other therapies for PE?
- Thrombolytic: reserved for patients with massive PE (clinically severe, severe cardio pulmonary compromise, i.e. hemodynamic instability, hypoxemia, RV dysfunction despite resuscitative efforts).
- Embolectomy
Summary of Pulmonary HTN
- Various causes and important to classify based on WHO grouping
- Treatment will be guided by etiology
- Progressive shortness of breath, loud P2
- Idiopathic Pulmonary Arterial HTN pathology is medial hypertrophy and intimal fibrosis
- Treatment with pulmonary vasodilators and lung transplant
Summary of DVT/PE
- Risk factors of prolonged immobility, hypercoagulable states etc.
- Symptoms of leg swelling, pain in DVT
- Sudden onset SOB+- pleuritic chest pain with hypoxemia in PE
- DVT diagnosed with venous compression ultrasonography
- PE diagnosed by spiral CT or V/Q scan
Summary of Pulmonary Vascular Disorders
- Treatment with anticoagulation (UFH, LMWH or Warfarin); Less commonly IVC filter, thrombolysis, embolectomy
- Major complications of heparin is Heparin induced thrombocytopenia
- Major complication of Warfarin is drug-drug interactions
