Pulmonary Vascular Disease Flashcards
Chest CT findings associated with PVOD
Triad of findings
1. mediastinal lymph node enlargement
2. smooth thickening of interlobular septa
3. ground glass centrilobular nodules
Which pneumocyte makes up largest percent of the alveolar surface area?
90% of alveolar surface area is by type I pneumocytes
about 3% of surface area by type II pneumocytes
2 functions of type 2 pneumocytes
- produce surfactant to reduce surface tension
- mitosis/replicate to replace damaged type I pneumocytes (type I pneumocytes cannot multiply)
Main component of surfactant
90% lipids
hydrophilic heads and hydrophobic tails to reduce surface tension
Differentiate epithelial layer that makes up bronchi vs. bronchioles
Trachea and bronchi are ciliated, pseudostratified columnar
While bronchioles are ciliated simple cuboidal
At what level of airway do you lose
(a) Cartilage
(b) Smooth muscle
(a) Trachea and Bronchi have cartilage, while bronchioles (and alveoli) don’t
(b) Smooth muscle present in trachea, bronchi, and bronchioles. No smooth muscle at level of the alveoli (duh too thin!)
Which level of airway has ciliated epithelial cells?
Trachea, bronchi, and bronchioles have ciliated epithelial layer
Lose cilia only once down at the alveolar level
Describe mechanism by which heliox can reduce work of breathing
Same viscosity but much lower density => lower Reynolds number (dimensionless unit that can predict if flow will be laminar or turbulent) => increased probability of laminar flow
In a pt with a Hb of 6 and SpO2 95%, PaO2 80, which would increase tissue oxygen delivery more:
Hb increase to 8 or
PaO2 to 100
B/c of O2 delivery and arterial O2 content equations- Hb increase to 8 would bring more oxygen to tissues
Formula for lung compliance
Measuring both chest wall and lung together (w/o esophageal balloon no way to separate)
Compliance = ease at which lung expands = dV / dP
Diagnostic BAL finding for DAH (aside from continuously bloody aliquots)
Specifically over 20% hemosiderin-laiden macrophages
-will stain blue with special Prussian-blue stain (stains iron)
What type of transplant specifically carries high risk of DAH
Autologous (self) bone marrow transplant associated with DAH
List some etiologies of DAH that do not involve capillaritis (capillary inflammation)
DAH without capillaritis
-malignancy
-severe mitral stenosis (pressure backs up)
-PVOD/PCH (pressure backs up)
-severe coagulopathy
-idiopathic pulmonary hemosiderosis
While DAH that definitely involve capillarities are the ANCA and CTD- associated, then anti-GMI and APLS can be with or without capillaritis
Differentiate mechanism by which ANCA vasculitis and anti-GBM disease causes DAH
ANCA vasculitis- causes inflammation of small vessels = pulmonary capillaries
While anti-GBM deposits antibodies against type IV collagen into the basement membrane/extracellular matrix- so different part of the alveolar/capillary interface involved
Differentiate treatment/management of DAH due to ANCA vasculitis vs. anti-GBM disease
DAH treatment
ANCA vasculitis- steroids and immunosuppression (mainly cyclophosphamide or rituximab if severe enough that there’s DAH)
while anti-GBM responds better to PLEX so typically start with steroids + cyclophosphamide + PLEX
Clinical triad of EGPA
EGPA clinical triad
- asthma–like airwy disease (often preceeds other things by years)
then - eosinophilia in tissues and systemically then
- small vessel necrosis (vasculitis)
Differentiate ANCA detection by immunofluorescence vs. ELISA
Immunofluorescence detects the ANCA in cytoplasmic vs. perinuclear pattern
Then the ELISA detects the antibody
p-ANCA typically seen with anti-MPO, in EGPA and MPA
then c-ANCA pattern typically accompanied by anti-PR3 in GPA
Which ANCA vasculitis is most likely to have
(a) Kidney involvement
(b) Granulomas
ANCA vasculitides: GPA, MPA, EGPA
(a) Renal involvement (glomerulonephritis) in GPA and MPA (not EGPA)
(b) GPA and EGPA- it’s int he name! granulomatous polyangitis (neutrophilic inflammation) vs. EGPA (eosinophilic granulomatous)
Common clinical features of GPA
(a) Systems typically involved
(b) Typical pulmonary findings
Granulomatous polyangiitis- small vessel vasculitis
(a) ENT/sinus, kidneys (glomerulonephritis), eyes (mononeuritis multiplex)
(b) Typically pulmonary findings = cavitary masses/nodules
Which ANCA vasculitis expect to see p- vs. c-ANCA (and which Ab does this correlate with?)
p-ANCA (perinuclear pattern of ANCA positivity on immunofluorescene) typically with anti-MPO Ab detected on ELISA
-seen in MPA and EGPA
vs.
c-ANCA (cytoplasmic pattern of ANCA positivity on immunofluorescnece) typically seen with anti-PR3 Ab on ELISA
-GPA
Unique drug used in treatment of EGPA not used in the other two ANCA vasculitis (not used in GPA or MPA)
Anti-IL5 mepolizumab approved for EGPA
While GPA and MPA use steroids MTX, cyclophosphamide (typically start with those in EGPA too but then can use mepo)
Differentiate treatment of limited vs. severe ANCA-associated vasculitides
Limited (no life or organ threatening involvement): start with steroids and methotrexate
Severe (life or organ threatening, DAH, glomerulonephritis, any CNS or eye involvement): pulse steroids and then either rituximab or cyclophosphamide
Which leg more common for DVT during pregnancy? Why?
L leg DVT more common b/c of compression of the L iliac vein by the R iliac artery
Mechanism of tPA
tPA (alteplase) binds to fibrin on surface of the clot and converts trapped plasminogen to plasmin that then breaks down clot
Aside from bleeding, major adverse effect to monitor for with protamine
Protamine (reversal for heparin and lovenox)- beware of sudden/severe hypotension and bradycardia
Differentiate proximal and distal DVT
Proximal = iliac, femoral, or popliteal vein involved
Distal = below the knee involving the calf veins with NO proximal component, tibial and peroneal veins
EKG findings c/w RV strain for massive PE
- RVH
- S1Q3T3
- TWI anteriorly (V1-V4)
Virchow’s triad
Virchow’s triad of clotting
1. disturbed blood flow
2. endothelial cell injury
3. hypercoagulable state
Most common mutations seen in heritable PH
- BMPR2
- ALK-1
Differentiate WHO FC II and III
FC II- dyspnea with normal activity
FC III- dyspnea with less than normal activity
Define vasoreactivity in PH
Vasoreactivity: drop in mPAP by at least 10 to under 40mmHg with unchanged or increase in cardiac ouptut
Characteristic histopathologic lesion in severe PAH
Characteristic plexiform lesion in later stage arteriolar remodeling
Which group of PAH drugs is associated with hepatotoxicity?
Hepatotoxicity in ERAs (endothelin receptor antagonists)
Bosentan, macitentan, ambrisentan
Which group of PAH drugs causes teratogenicity?
ERAs (endothelin receptor antagonist) and SCG stimulator (soluble guanylate cyclase stimulator) are both teratogenic
Which group of PAH drugs is contraindicated with use of nitrates?
PDEi due to hypotension
Physiologic difference between PAH and PVOD
PAH- arteriolar thickening/inflammation vs.
PVOD- obstructive vascular remodelling of the pulmonary capillary venules
Describe main histopathologic features of pulmonary vasculopathy in PH
Histopath features
-intimal proliferation
-thrombosis
-medial hypertrophy
-vasoconstriction
-plexiform lesions
Most common identified pathogen associated with acute chest syndrome
Chlamydia pneumoniae
Which PH drug is avoided in patients with sickle-cell related PH?
Tadalafil b/c associated with increased hospitalizations for pain crises (acute vasoocclusive crisis)
Differentiate orthodeoxia and platypnea
Hepatopulmonary disease
-orthodeoxia = hypoxia worse when upright
-platynpnea = dyspnea (subjective feeling) worse when upright
Diagnostic cutoffs for hepatopulmonary syndrome
(a) A-a gradient
(b) PaO2 on room air
HPS Cutoffs
(a) A-a gradient over 15
(b) PaO2 on room air under f80
-then PaO2 under 60 is a MELD exception to move pts up on transplant list
Recommend nonpermanent contraception option for females with PH
Progestin-only IUD/implantable device
-over progestin-only OCPs b/c unreliability of daily pill
-avoid estrogen-containing compounds due to possible deleterious effects of estrogen on pulmonary vasculature and known increase risk of clot
SEEK question even recommended hysteroscopic sterilization, or surgical sterilization of male partner if monogamous
Duration of anticoagulation for DVT in pregnancy
Lovenox for at least rest of pregnancy + 6 weeks post partum for minimum 3 months
Discharging pt with low-risk DVT straight from ED- why use rivaroxaban over dabigatran?
Dabigatran requires 5 day overlap with parenteral (IV) so can’t discharge from ED
4 T’s in the T-score for HIT
HIT score
1. thrombocytopenia- degree of plt drop
2. timing- not immediate (b/c antibodies not formed yet) unless heparin w/in last 30 days
3. thrombosis
4. oTher reason for thrombocytopenia
HIT
(a) Expected platelet drop
(b) Expected timing
HIT
(a) Most consistent if plt drop by ~50% and not to below 50k
Less likely if 10-30k nadir
very unlikely if nadir under 10
(b) Timing- 5-10 days, or within 1 day if exposure to heparin within the past 30 days
Pt with cancer and VTE who won’t do injections- edoxaban or warfarin?
Edoxban, apixaban, and rivaroxaban all also good for malignancy-associated clot
-lower risk of bleeding (and obv way easier to use) than warfarin
Main reason for post-op hypoxia after PTE within first 12-48 hrs
Reperfusion lung injury- 30% risk in pts within 48 hrs of PTE surgery due to high permeability edema
-look for imaging opacification in areas that we’re reperfused during surgery
Formulas and cutoffs for
(a) Transpulmonary gradient
(b) Diastolic pressure gradient
Helpful to differentiate group I and II PH
(a) TPG = mPAP - PCWP, abnormal if above 12-15
(b) Diastolic pressure gradient = PA diastolic - PCWP, abnormal if above 7
Formula and cutoff for PVR
PVR = TPG / CO
TPG = mPAP - PCWP
so PVR = (mPAP - PCWP) / CO
Abnormal if PVR is 3 or above
Describe pathophysiology of the 3 histopathologic patterns of DAH
(1) Pulmonary capillaritis
(2) Bland hemorrhage
(3) Diffuse alveolar damage
Diffuse alveolar hemorrhage
- Pulmonary capillaritis = neutrophilic infiltration and necrosis/breakdown of alveolar-capillary membrane => get leakage of RBCs into alveolar space
- Bland hemorrhage = alveolar septa is ok but tons of RBCs in alveolar space, so something else (either pressure overload or coagulopathy) and not a mechanical problem at the alveolar-capillary surface causing bleeding
- DAD/ARDS obv alveolar damage
Etiologies of each of the 3 histopathologic patterns of DAH
(1) Pulmonary capillaritis
(2) Bland hemorrhage
(3) Diffuse alveolar damage
DAH etiologies
(1) Pulmonary capillaritis- destroyed capillaries => leak of RBCs into alveolar space
-rheumatologic: SLE, MCTD
-systemic vasculitis: ANCA, IgA, cryoglobulinemia
(2) Bland hemorrhage- interstitium intact but RBCs fill alveolar space
-coagulopathy, thrombocytopenia
-high LVEDP: severe MR
(3) DAD: any cause of infection or ARDS
Mechanism/pathophysiology of DAH in
(a) ITP
(b) Severe MR
(c) ANCA vasculitis
Diffuse alveolar hemorrhage
(a) ITP (and other causes of severe thrombocytopenia) or coagulopathy causes bland hemorrahge- interstitium/capillary membrane intact but RBCS fill alveolar space
(b) Severe MR (and other causes of elevated LVEDP) cause bland hemorrhage
(c) ANCA vasculitis (and other systemic vasculitides) cause pulmonary capillaritis (breakdown/necrosis of alveolar/capillary membrane allowing RBC leakage)
Name 2 etiologies of DAH that can cause DAH by two possible mechanisms (both pulmonary capillaritis and bland hemorrhage)
DAH from SLE (lupus) and anti-GBM can be from two mechanisms: both pulmonary capillaritis (breakdown of alveolar/capillary membrane => RBCs leak) or bland hemorrhage (interstitium intact but RBCs still fill alveolar space)
Mechanism/pathophysiology of DAH in
(a) Autologous hematologic stem cell transplant
(b) Idiopathic pulmonary hemosiderosis
DAH
(a) Autologous hematologic stem cell transplant causes pulmonary capillaritis = breakdown of alveolar/capillary membrane => RBCs leak into alveolar space
(b) Idiopathic pulmonary hemosiderosis causes bland hemorrhage (interstitium intact but RBCs still fill alveolar space)
General treatment approach for DAH
DAH treatment: generally start with pulse dose steroids (500 to 1g of methylpred daily), then think of other immunosuppression typically cyclophosphamide depending on suspected etiology
Specifically etiology tx:
-if suspect anti-GBM: PLEX
-if suspect ANCA vasculitis: pulse steroids –> cyclophosphamide
-cryoglobulinemia: treat underlying virus (hepatitis, HIV)
Differentiate treatment of DAH due to systemic vasculitis (GPA, MPA) from anti-GBM
DAH due to systemic vasculitis and anti-GBM both warrant immunosuppression- both likely start with pulse steroids (methylpred 500-1g daily x3 days)
then ANCA-vasculitis: cyclophosphamide or rituximab
vs.
anti-GBM- PLEX + cyclophosphamide (PLEX much better in anti-GBM not very helpful in ANCA-vasculitis)
Differentiate two histopath patterns of DAH
DAH has 3 distinct histologic patterns
- Bland hemorrhage (Left image): RBCs in alveolar space with normal interstitial space/alveolar septa
Etiologies: elevated LVEDP (severe MR), coagulopathy (ITP, antiplatelets) - Pulmonary capillaritis (Right image): interstitial neutrophilic infiltrate (red arrows), disruption of alveolar-capillary basement membrane => accumulation of RBC in alveolar space
Etiologies: systemic vasculitis (ANCA, HSP, IgA nephropathy), rheumatic disease (anti-GBM, MCTD, SLE) - DAD from drugs/toxins, infection (anything that can cause ARDS)
Why not use both riociguat and sildenafil together for PH treatment?
Both are nitric oxide potentiators which are potent vasodilators => together would have too much hypotension
Activity of the following hormones in PH pathophysiology
(a) Endothelin
(b) NO
(c) Prostacyclin
(a) Endothelin => vasoconstriction, proliferation of smooth muscle
(b) NO => vasodilation and antiproliferation
(c) Prostacyclin => vasodilation and antiproliferation
Differentiate mechanism of riociguat and selexipag
Riociguat = soluble guanalyne cyclase stimulator
Increase NO
Selexipag = oral prostacyclin receptor agonist
Prostacyclin => vasodilation and antiproliferation
Main 2 side effects of endothelin receptor antagonists
ERAs
- teratogenic (also riociguat) => monthly pregnancy test require for Rx
- edema
Which 2 classes of PH drugs must be avoided in pregnancy?
ERAs and riociguat- both require monthly pregnancy tests for prescription
Main side effects of PDE5 inhibitors
SIldenafil/tadalafil
Flushing, headache, hypotension
Which PH drug carries side effect of
(a) Epistaxis
(b) Liver injury, treatment requires monthly LFTs
PH drug
(a) Epistaxis with tadalafil
(b) Monthly LFTs require for bosentan given risk of liver injury
Describe vasodilatory side effects of prostacyclin agonists
Side effects of prostacyclins:
headache, flushing, hypotension, jaw pain, nausea
then rebound if you stop it… (so don’t let those pumps run out!)
Describe typical initial treatment regimen for low or intermediate risk PH
Low/intermediate risk PH- typically start with combo oral meds:
ERA + SGC stimulator or PDEi
ex: maci/rio
