Pulmonary Vascular Diseases Flashcards
What are the small-vessel vasculitis?
ANCA associated (GPA, MPA, EGPA)
Immune complex associated (cryoglobulinemic, hypocomplementemic urticarial, Goodpastures, IgA)
What are the medium-vessel vasculitis?
PAN
Kawasaki disease
What are the large-vessel vasculitis?
Takayasu
Giant cell arteritis
45 y/o white male presents with sinusitis, hemoptysis, uveitis, and hematuria. Renal biopsy reveals crescentric segmental necrosis with pauci-immune immunofluorescence. Antiproteinase ANCA positive. Diagnosis?
GPA
38 y/o female from Italy presents with hypoxemia and is intubated. Bronchoscopy reveals DAH. She has worsening renal failure and biopsy reveals crescentric segmental necrosis. Serum is MPO-ANCA+. Diagnosis?
MPA
28 y/o female presents with worsening neuropathies and asthma symptoms. CT biopsy of lung nodules reveals necrotizing eosinophilic granulomatosis. Serum is MPO-ANCA+. Diagnosis?
EGPA
What medications are known to “unmask” EGPA when started?
Leukotriene inhibitors
Mainstay of medical treatment in all ANCA vasculitis in standard therapy with limited disiease (2 meds)?
Steroids and methotrexate
If an ANCA vasculitis has severe disease, you drop the methotrexate and add on what medications for each ANCA vasculitis?
GPA - steroids + cyclophosphamide (or rituxan)
MPA- steroids + rituxan
EGPA steroids + cyclophosphamide or rituxan or anti-IL-5
Mainstay of medical treatment in all ANCA vasculitis in remission in limited disease (2 meds)?
MTX or AZA
Mainstay of medical treatment in all ANCA vasculitis in remission in refractory disease?
Some combo of steroids + rituxan/cyclophosphamide (except no CYC in MPA) and plasma exchange
How often are pulmonary features seen in giant cell arteritis?
25%
lung nodules, interstitial infiltrates, bronchocentric granulomas
How often is pulmonary HTN seen in Takayasu arteritis?
50%
What infections is PAN associated with?
HBV
HCV
True/False: PAN is often associated with DAH as one of its complications
FALSE
This never causes capillaritis, so consider another cause.
Since lungs are affected in 50% of the population in anti-GBM disease, what is a common presenting symptom?
DAH
Although cryoglobulinemic vasculitis associated DAH is only seen in ~3% of patients, what is its mortality rate?
80%
Treatment of cryoglobulinemic vasculitis?
Rituxan
What % of patients with DAH present with hemoptysis?
30%
Tell me the 2 things that causes DAH with pulmonary capillaritis?
AAVs (GPA, MPA, EGPA)
Connective tiissue disorders (SLE, RA, mixed connective tissue disorders, Behcet disease, polymyositis, IgA-associated vasculitis)
Tell me the 4 things that causes DAH with or without pulmonary capillaritis?
Goodpastures
SLE
Antiphospholipid syndrome
Drug-induced DAH
Tell me the other things that causes DAH withOUT pulmonary capillaritis?
Malignancies LAM PVOD Pulmonary capillary hemangiomatosis Mitral stenosis Inhalation toxins (crack, trimetallic anhydride) Idiopathic pulmonary hemosiderosis Drugs (anticoagulation, abciximab, ATRA, sirolimus)
Is DAH more commonly
found in autologous or
allogenic BMT?
Autologous BMT
Treatment of DAH?
High dose steroids (500mg-2g/day) for 5 days followed by gradual tapering and maintenance
Since DAH associated with antiphospholipid syndrome has rapidly progressive respiratory failure and a high mortality rate, what therapy might be indicated in the treatment in addition to steroids?
Early plasma exchange
Case: 15 y/o presents with recurrent hemoptysis and GGO’s on imaging. Labwork reveals iron-deficiency. Bronchoscopy is performed and biopsy shows bland-lung histopathology with fibrosis. Diagnosis?
Idiopathic pulmonary hemosiderosis (IPH)
Treatment of IPH?
Immunosupression, plasma exchange, and gluten-free diet.
What is Lane-Hamilton
syndrome?
Association of gluten-sensitive sprue (celiac sprue) with idiopathic pulmonary hemosiderosis. Only 18 cases are described in the literature. All IPH patients should be screened for sprue with serologies (antigliadin and antiendomysial antibodies). Gluten-free diet seems key to therapy and prevention of relapses.
Sensitivity/specificity of the following testing methods for PE?
D-Dimer
V/Q scan
Spiral CTA
Extremity US
D-Dimer 96/40
V/Q scan 77/98
Spiral CTA 83/96
Extremity US 29/97
Case: 25 y/o woman who is 34 weeks pregnant presents with dyspnea. No LE swelling or pain. You’re concerned for PE. CXR ordered and shows right lung opacity. Whats the next test?
CTPE
Abnormal CXR means you can’t do a V/Q, and high pre-test probability means you should proceed with the CT PE
Tell me the following anticoagulant based on the following mechanism of action:
Binds ATIII and factor Xa
Heparin
Tell me the following anticoagulant based on the following mechanism of action:
Binds factor Xa»_space;» ATIII
Enoxaparin
Tell me the following anticoagulant based on the following mechanism of action:
Blocks vitakin K epoxide, slow decrease in factors II, VII, IX, X, and thrombin
Warfarin
Tell me the following anticoagulant based on the following mechanism of action:
Direct thrombin inhibitor
Argatroban
Tell me the following anticoagulant based on the following mechanism of action:
Oral factor IIa inhibitor
Dabigatran
Tell me the following anticoagulant based on the following mechanism of action:
Oral factor Xa inhibitor
Rivaroxaban (or the others of course)
Tell me the following anticoagulant based on the following mechanism of action:
Increased plasminogen, which increases plasmin and therefore breaks down fibrin
Thrombolytic therapy (streptokinase, urokinase, tPA)
Mortality rates for the following scenarios in PEs?
RV dysfunction, no hypotension
Hypotension
Cardiogenic shock
Cardiopulmonary resuscitation
RV dysfunction, no hypotension - 8%
Hypotension - 15%
Cardiogenic shock - 25%
CPR - 65%
Fill in the blank for “potential” indications for tPA in PE:
Severe \_\_\_\_ Large perfusion defect on \_\_ scan Extensive \_\_\_ \_\_\_ on CT \_\_ dysfunction Free-floating RA or ventricular \_\_\_ PFO CPR
Severe HYPOXEMIA Large perfusion defect on CT scan Extensive EMBOLIC BURDEN on CT RV dysfunction Free-floating RA or ventricular THROMBUS PFO CPR
Fill in the blank for indications for tPA in PE:
Persistent ___
Shock
Massive proximal LE ___ associated with severe swelling or limb ischemia
Persistent HYPOTENSION
Shock
Massive proximal LE THROMBUS associated with severe swelling or limb ischemia
Fill in the blank for relative contraindications for tPA in PE:
Severe uncontrolled HTN (BP >___)
Hx of prior ___ not covered in absolute contraindications
Current use of ___; known bleeding diathesis
Recent trauma (within 2-4 weeks), prolonged CPR (>10 mins) or major ___ within 3 weeks
Noncompressible vascular punctures
Recent (2-4 wks) __ bleeding
Pregnancy, PUD
Severe uncontrolled HTN (BP >180/110)
Hx of prior CVA not covered in absolute contraindications
Current use of ANTICOAGULANTS; known bleeding diathesis
Recent trauma (within 2-4 weeks), prolonged CPR (>10 mins) or major SURGERY within 3 weeks
Noncompressible vascular punctures
Recent (2-4 wks) INTERNAL bleeding
Pregnancy, PUD
Fill in the blank for ABSOLUTE contraindications for tPA in PE:
Previous ___ stroke at ___; other stroke or cerebrovascular events within 1 year
Known intracranial ___
Active ___ bleeding
Suspected ___ dissection
Previous HEMORRHAGIC stroke at ANY TIME; other stroke or cerebrovascular events within 1 year
Known intracranial NEOPLASM
Active INTERNAL bleeding
Suspected AORTIC dissection
How is pulmonary vascular
resistance calculated in
Wood units?
(mPAP – PCWP) ÷ cardiac
output (L/min) = PVR in
Wood units
What is the most common
cause of pulmonary
hypertension?
Left-sided systolic or diastolic heart disease (WHO Group 2), although this represents pulmonary venous hypertension rather than pulmonary arterial hypertension.
What are common
drugs/toxins implicated in
pulmonary hypertension?
Aminorex, fenfluramine,
dexfenfluramine,
amphetamines,
methamphetamines
Mutations in what gene are detected in ~70% of PAH cases and 11-40% of IPAH patients?
BMPR2
Also see ALK-1 mutations
What are the 3 main pathways that cause PAH?
think medication targeted pathways
Endothelin pathway (endothelin-1) NO pathway Prostacyclin pathway (PI2)
Imbalance of vasoconstriction + proliferation and vasodilation + anti-proliferation is what causes PAH. Which pathways are vasoconstrictive, and which are vasodilatory?
Vasocontrictive/proliferative = endothelin pathway
Vasodilatory/anti-proliferative = NO, PI2
Tell me the 4 WHO functional classifications for PAH.
Class I - no limitation on activity
Class II - slight limitation on activity, usually some symptoms with activity
Class III - marked limitation on activity, comfortable at test, symptoms with any activity
Class IV - symptoms at rest, unable to perform activities
How is a positive
vasoreactivity test defined
during RHC?
A positive response to therapy with vasodilators is defined as a fall in mean PAP of > 10 mm Hg to reach a mean PAP of < 40 mm Hg with an increased or unchanged cardiac output.
How does one establish a
definitive diagnosis of
PAH?
With RHC showing a mPAP ≥ 25 mm Hg with pulmonary capillary wedge pressure ≤ 15 mm Hg and pulmonary vascular resistance > 3 Wood units (240 dynes/sec/cm5).
What medciations can be trialed if patient has a positive vasoreactivity testing?
CCBs
Which group of drugs is
associated with
hepatotoxicity?
Endothelin receptor
antagonists (ERAs)
Which group of drugs is
contraindicated with the
use of nitrates?
Phosphodiestrase-5 (PDE-
5) inhibitors
Which group of drugs
causes teratogenicity?
Endothelin receptor
antagonists (ERAs)
Tell me the 3 prostanoids
Epoprostenol (IV)
Iloprost (inhaled)
Treprostinil (IV, SC, inhaled)
Tell me the 3 ERAs
Bosentan
Ambrisentan
Macitentan
Tell me 2 PDE-5 inhibitors
Sildenafil
Tadalafil
Tell me the 1 soluble guanylate cyclase stimulator
Riociguat
Based on the following adverse effects, which PROSTANOID am I talking about?
Flushing, headache, nausea, vomiting, thrombocytopenia, hypotension, jaw pain
Epoprostenol
Based on the following adverse effects, which PROSTANOID am I talking about?
Flushing, cough, headache, nausea, flu-like illness
Iloprost
Based on the following adverse effects, which PROSTANOID am I talking about?
Site pain and erythema in SC administration, headache, nausea, diarrhea, cough(inhaled)
Treprostinil
Based on the following adverse effects, which ERA am I talking about?
Hepatotoxicity (stop if bilitubin 2x ULN, AST/ALT 3x ULN), edema, nasopharyngitis, teratogenic
Bosentan
Based on the following adverse effects, which ERA am I talking about?
AST/ALT elevation (stop if >8x ULN), edema, headache, nasal congestion, flusing, teratogenic
Ambrisentan
Based on the following adverse effects, which ERA am I talking about?
URI, edema, nasopharyngitis, headache, anemia, AST/ALT elevation, teratogenic
Macitentan
Based on the following adverse effects, which PDE-5 inhibitor am I talking about?
Headache, dyspepsia, flusing, epistaxis, optic neuritis (rare), potentiates hypotension with other meds
Sildenafil
Based on the following adverse effects, which PDE-5 inhibitor am I talking about?
Headache, flushing, respiratory infections, extremity pain, avoid if renal or hepatic impairment
Tadalafil
What are the side effects of Riociguat?
Headache, dyspepsia, nausea, peripheral edema
Which of these categories of PAH has the best prognosis? A. PAH associated with congenital heart disease B. PAH associated with scleroderma C. PAH associated with HIV D. PAH associated with liver disease
A. PAH associated with
congenital heart disease.
PASP > what value is suggestive of CTEPH?
> 50mmHg
What test is the gold standard to diagnose CTEPH?
VQ scan
Treatment of CTEPH?
Pulmonary endarterectomy
Riociguat (in those who are not surgical candidates)
Anticoagulation (duhhh)
This type of pulmonary HTN is where there is fibrotic remodeling of the intima of preseptal pulmonary venules and interlobular septal veins which causes flow obstruction, often with intaluminal fibrosis.
PVOD
What gene plays a role in
the pathogenesis of
PVOD?
BMPR-2
True/False: PVOD can also affect pulmonary arterioles resulting in similar remodeling as IPAH.
TRUE
The only difference is that PVOD usually lacks arteriolar plexiform lesions
So since PVOD can look like PAH on cath and what not, what changes on the following items supports PVOD as the diagnosis?
Chest imaging
BAL results
Response to PAH therapy
Imaging has pulmonary edema with a normal PCWP
BAL shows alveolar hemorrhage
PAH-specific therapy causes the development of pulmonary edema
Treatment of PVOD?
Still use PAH-specific treatments but you have to be careful as they usually get pulmonary edema, so keep them in the ICU while you diurese them
Prognosis of PVOD?
1 year mortality is 72%, so early transplant referral
What is seen on imaging for acute chest syndrome in sickle cell disease?
Usually consolidation involving 1 complete lung segment
Treatment of acute chest syndrome?
Supportive:
Analgesics Hydration Supplemental O2 Blood transfusion ISB Antibiotics SABAs for bronchospasm Exchange transfusion for severe illness
What is the most common
pathogen identified in
patients with acute chest
syndrome?
Chlamydia pneumoniae
Treatment of fat emboli syndrome?
Supportive
Exchange transfusion if severe
What molecule is felt to be primarily responsible for the intrapulmonary vascular dilations seen in HPS?
NO
What is the most
commonly used method for
confirming IPVD in HPS
patients?
Contrast enhanced
transthoracic echo
What intervention has been
shown to improve
oxygenation and survival in
HPS patients?
Liver transplantation
What herb has been shown to have some improvement in PaO2 in HPS?
Garlic
