pulmonary circulation disorders Flashcards
what is a PE
An obstruction of the pulmonary artery or one of its branches by an embolus
what is the 3rd leading cause of mortality in hospitalized pts
PE
also the 3rd MC CV cause of death
what are types of PEs
- thrombus - arising from any area of venous circulation (MC DVT)
- air - during neurosurgery, central venous catheters
- amniotic fluid - during active labor
- fat - long bone fractures
- foreign bodies - talc in injection drug users, cement emboli (joint replacement)
- parasite eggs (schostosomioasis)
- septic emboli - acute infective endocarditis
- tumor cells - RCC
what is the pathophysiological response from pulmonary vascularobstruction
- infarction (MC when small emboli lodge distally)
- impaired gas exchange leading to hypoxia
- cardiovascular compromise
how does impaired gas exchange lead to hypoxia
- altered ventilation perfusion ratio
- Inflammation → Surfactant dysfunction → Atelectasis → Functional intrapulmonary shunting
- Stimulation of the respiratory drive → hypocapnia and respiratory alkalosis
how does cardiovascular compromise occur from pulmonary vascular obstruction
- Obstruction of the vascular bed → Increased pulmonary vascular resistance → Right heart and intraventricular septal strain
- Less blood returning to the left ventricle → Reduced cardiac output → Hypotension
what is virchows triad
MC pulmonary embolism risk factors
what is considered in venous stasis
- immobility (acute loss of ability to walk)
- hyperviscosity (polycythemia)
- inceased central venous pressures (low CO states, pregnancy)
what is considered in the risk of injury to vessel walls
- prior thrombosis
- orthopedic surgery
- trauma
what are factors that affect hypercoagulability
- medications (OCP, hormonal replacement)
- Disease (malignancy, surgery)
- inherited gene defects
what are the inherited gene defects that could lead to hypercoagulability
- Most common is Factor V Leiden ¹
- Deficiency of dysfunction of protein C, protein S, and antithrombin
- Prothrombin gene mutation
- Hyperhomocysteinemia²
- Antiphospholipid antibodies
what are the MC signs and sympotms of PE
- sudden onset dyspnea
- pleuritic chest pain
- cough
- (sudden onset pain is related to small PEs that cause infarctions)
- tachypnea!!!!!! Most reliable exam finding
what is meant by “pleuritic” chest pain
Chest pain worse with breathing ( i know most people may know this but i didnt lol)
what may precede s/s of PE
s/s of DVT such as lower leg pain or “charley horse” in calf. also swelling/warmth/erythema of the lower leg.
why are PEs known as the “great masquerader”
because symptoms are often non specific. they can range from asymptomatic to shock and sudden death.
vary based on size of emboliand baseline of cardiopulm status
what is the MC sign and the MC symptom in PE
symptom - dyspnea
sign - tachypnea
what are the wells criteria for PE
idk if we need this
what is the “pre-test” probabilities determined by wells criteria
> 6 points = high risk (78.4%)
2–6 points = moderate risk (27.8%)
<2 points = low risk (3.4%)
when is PERC rules used
only when wells is LOW risk!
what are the PERC rules ?
yes, we need this
what testing should be done when a patient has low wells risk and no PERC rules criteria
none
what testing should be done when a patient has low wells risk and 1 positive PERC rule OR if they just have intermediate wells risk
high sensitivity plasma D-dimer
normal -> no imaginge
high –> imaging
what testing should be done in a patient with a high risk wells score
imaging (skip D diemr)
how reliable is D-dimer testing
high sensitivity (95-97%) and low-moderate specificity (45%)
what is D-dimer
a protein fragment from a broken down blood clot
what is normal D-dimer and when is it adjusted
- Normal: < 500 ng/mL
- Adults over age 50 with a low or intermediate clinical probability of PE use an age-adjusted threshold (age × 10 ng/mL)
what could create a false positive in D-dimer results
- age >50 years
- recent surgery or trauma
- acute illness
- pregnancy or postpartum state
- rheumatologic disease,
- renal dysfunction
- sickle cell disease
are D-dimer elevations diagnostic?
no!! must get imaging
what is the first line imaging modality in most PE pateints
CTA (requires IV contrast)
+ result is a filling defect
when should you use caution in a CTA
- pregnancy
- metformin
- allergy to dye
what are indications for VQ scans in PE patients
- pregnancy
- renal insufficiency
- severe prior adverse rxn to contrast
what are the interpretations seen in PE for VQ scan
- normal perfusion rules out PE
- reduced perfusions with normal ventilation means PE is likely
what is the gold standard for PE diagnosis
pulmonary angiography
this is safe but INVASIVE requiring interventional radiology and contrast dye
what is a positive PE results in a pulmonary angiography
+ intraluminal filling defect
when is pulmonary angiography indicated
when there is high pre-test probability and inconclusive CTA results
what are additional labs that may be ordered in PE suspicion and what would they show
- CBC - leukocytosis
- ABG - low PO2, respiratory alkalosis with hypocapnia.
- Troponin and BNP - elevated in 25-50%, related to PE size causing RV myocardial stretch)
what are EKG abnormalities that may be seen in PEs
- sinus tachycardia (MC)
- non-specific ST seg and T-wave changes (MC)
- S1Q3T3 (poor prognosis)
- RV strain/R axis dev (poor prognosis)
- new incomplete RBBB (Poor prognosis)
when is a chest radiograph used to assess PE
often ordered to rule out other etiologies in the workup
what nonspecific findings are common in chest radiograph?
nonspecific findings common:
- cardiomegaly
- basilar atelectasis
- infiltrate
- pleural effusion
what are the less common (<5%) findings in chest radiographs
- westermarks sign
- hamptons hump
what is westermarks sign
an area of lung oligemia - usually from complete lobar artery obstruction
(14% sensitivity, 92% specificity)
what is hamptoms hump?
dome-shaped dense opacification in the periphery of the lung - indicative of pulmonary infarction
(22% sensitivity, 82% specificity)
when are lower extremity venous dopplers used
to assess for evidence/location of DVT
what percent of paients with PE have a DVT evident on evaluation
70%
what is the risk stratification for high risk PE (massive)
what is the risk stratification for intermediate risk PE (sub-massive)
what is the risk stratification for low risk PE (less severe)
what is the intial management for PE
- supplemental oxygen
- ventilatory support
- hemodynamic support
!!!avoid excessive IV fluids → increased risk of right sided heart failure!!!
what are the three primary forms of therapy for PE
- anticoagulation
- fibrinolysis
- thrombectomy
how much will anticoagulation reduce mortality for PE
will reduce PE mortality rate to <5%
what medications could be used for anticoagulation management of PE
- unfractionated heparin
- low molecular weight heparin
- Direct acting oral anticoadulants (DOACs)
- fondaparinux
- warfarin
what is the MOA of unfractionated heparin
Binds to and accelerates the activity of antithrombin, preventing additional thrombus formation
what monitoring is required when a patient is on unfractionated heparin
obtain aPTT every 6 hours during tx (goal of 60-80s)
when is anticoagulation given in high risk patients
prior to imaging confirming diagnosis
who is unfractionated heparin reserved for
- unstable patients
- severe renal insufficiency
what is the dose for unfractionated heparin? (she said we DO need to know this)
- 80 units/kg/dose IV x 1 followed by 18 units/kg/hour (max 2000u/hr)
what is the risk associated with unrfactionated heparin and how do we reverse its effects
- risk of hemorrhage
- protamine sulfate reverses effects (indicated only for life threatening or intracranial bleed)
what is the LMWH medication
enoxaparin (lovenox)
who is LMWH preferred in
Preferred over other injectable agents in those who can not take oral anticoagulants
- greater bioavailability, more predictable dose response, longer half life than UFH
who must you monitor when giving LMWH
Monitoring only in obese, underweight (<45 kg) or renal impairment
what is the risk associated with LMWH and how do we reverse its effects
- risk of hemorrhage
- protamine sulfate reverses effects (indicated only for life threatening or intracranial bleed)
what are the DOACs
factor Xa inhibitors:
- rivaroxaban(xarelto)
- apixaban (eliquis)
direct thrombin inhibitors:
- dabigatran (pradaxa)
what is dosing for rivaroxaban (xarelto) and apixaban(eliquis)
Xarelto - BID then QD after 21 days
Eliquis - BID
what is the reversal agent for Factor Xa inhibitors
AndexXa
used for life-threatening or uncontrolled bleeding
what monitoring must be done for factor Xa inhibitors
No lab monitoring, few drug-drug or drug-food interactions
what is the dosing for dabigatran (pradaxa)
BID
what bridging is required with factor Xa inhibitors
NONE
what bridging is required for direct thrombin inhibitors (dabigatran/pradaxa)
- requires 5-10 days of bridging with UFH/LMWH
what is the reversal agent for dabigatran (pradaxa)
praxbind
what is fondaparinux (arixtra)
injectable factor Xa inhibitor that is once daily SQ dosing
what is preferred anticoag if a patient has a hx of HIT
fondaparinux (arixtra)
otherwise its less preffered than LMWH
what is warfarin
Vitamin K antagonist prevents activation of coagulation factors II, VII, IX, and X
how long does it take for warfarin to reach full effects
5 days
what is the bridging term for warfarin
requires bridging with LMWH until INR is 2-3
what monitoring is required fro warfarin
Monitoring required: adjust to keep INR between 2-3
Often requires variable dosing regimens that changes frequently
what is a down side of warafarin
interacts with other foods and drugs
what medications are given for fibronolysis
- tissue plasminogen activator (tPA) - Alteplase
what is the indicaiton for tPA
- high risk PE patients
- intermediate risk PE with elevated trop or BNP or if they have persisiten hypoxemia with distress
what are contraindications for tPA
- intracranial disease
- uncontrolled HTN >220/110 at presentation
- recent major surgery or trauma (3 wks)
- ischemic CVA in last 3 mo
- metasatic cancer
what is embolectomy
Manual removal of the emboli surgically or with a catheter
what are indications for an embolectomy
Hemodynamically unstable patients with a contraindication or failure to respond to tPA
what benefit is seen with catheter-directed embolectomy procedures
locally injecting tPA at a lower dose decreasing bleeding risk
what can be done to prevent PE
- IVC filter with a goal to prevent PE recurrence
what is the indication for an IVC filter
- active bleeding that prevents anticoagulation (wWHAT)
- recurrent VTE despite intensive anticoagulation
what are indications for inpatient treatment in PE patients
- severe illness or presence of comorbidities
- assocaited DVT
- educational needs (lack of knowledge about PE and management)
- problematic social situations (prior noncompliance with follow up care)
OR ANYTHING IN THIS PICTURE
what is the duration of anticoagulation with PE? what considerations go into this decision?
3-6 months minimum vs indefinite anticoagulation
- provoked or unprovoked PE?
- presence of risk factors for PE?
- estimated risk of bleeding and recurrence?
- patients preferences and values?
if no obvious cause for venous thromboembolism is determined, what should be done
evaluate for any of the following and consult hematology
- antithrombin III deficiency
- protein C and S deficiency
- lupus anticoagulant
- homocystinuria
- occult neoplasm
- connective tissue disorders
what type of system is the pulmonary circulation
low pressure, low resistance
(mean pulm arterial pressure shouls be 10-18mmHg)
this means its able to accommodate significant increase in blood flow during exercise
seriously billie go watch this
https://www.youtube.com/watch?v=WVCOHGHWSG0
what is the pathophysiology of pulmonary HTN
Pathophysiology: Increase in pulmonary vascular resistance, typically due to vasoconstriction, remodeling, and thrombosis of the small pulmonary arteries and arterioles leading to hyperplasia and hypertrophy of the vessels.
what is pulmonary HTN (like the actual mPAP value)
mPAP>20 mmHg
what is the WHO classification for group 1 pulm HTN
- idiopathic PAH
- hereditary PAH
- drug induced PAH
- connective tissue disease assocaited PAH
- congenital heart disease assocaited PAH
- HIV
what is the WHO classification for group 2 pulm HTN
- d/t left sided heart disease
- risk factors for this type of PH include:
- CAD
- HTN
- DM
-high cholesterol ect.
what is the WHO classification for group 3 pulm HTN
- PH d/t lung disease or hypoxia
- can be caused by advanced lung disease including:
- COPD
- interstitial lung diseases
- OSA
what is the WHO classification for group 4 pulm HTN
- chronic thromboembolic pulmonary HTN is MCC of group 4 PH
what is the WHO classification for group 5 pulm HTN
this is a miscellaneous group that includes causes of PH that are unclear or have multiple mechanisms such as sarcoidosis
what are symptoms of pulmonary HTN
- malaise/fatigue (MC)
- dyspnea (MC, starts as exertional but then progresses to resting)
- anginal pain
- non productive cough
- hemoptysis (rare, life threatening, results as PA rupture)
- exertional syncope (severe cases where CO is affected)
what are PE findings in Pulmonary HTN
- odten normal in early disease
- late disease presents w following:
- JVD
- accentuated P2
- 3rd heart sound (kentucky)
- tricuspid regurgitant murmur
- hepatomegaly
- lower extremity edema
- cyanosis
what does the 3rd “kentucky” heart sound result from in pulmonary HTN
dysfunctional right ventricular wall
what are initial workup studies for PHTN
- CXR/CT
- EKG
- 2D transthoracic echo w doppler
what is seen on EKG for pulm HTN
- signs of RVH maybe
what is seen on a CXR/CT for pulm HTn
- may be normal
- enlargement of pul arteries
what is the gold standard for diagnosing pulm HTN
right sided heart catheterization aka swan ganz catheter
what mPAP pressure is diagnostic for PH
mPAP>20mHg
What is seen on 2D transthoracic echocardiograms with doppler in pulm Hypertension
signs of PH such as:
- elevated estimated pulm artery systolic pressure
- triscuspid regurgitation
- RV enlargement
- wall thickness
- dysfunction
NORMAL ECHO DOES NOT RULE OUT PH
what does pulmonary capillary wedge presure assess
left sided heart disease
- 15 or less = no left sided heart disease
- elevated PCWP usually indicates left sided heart disease and should be confirmed with a left heart cath
what is vasodilator response
after injection of a vasodilator pressures are remeasured
drop of mPAP of 10-40 mmHg indicative of positive vasodilator response
what are diagnostics used to look for less common etiologies of pulmonary hypertension
- CBC
- CMP
- Coags -pT, apTT
- ABG
- HIV testing
- Hepatitis panel
- Urine toxicology
what are the collagen-vascular disease screening labs done in evaluation of pulmonary hypertension
- antinuclear ab (ANA), rheumatoid factor (RF), antineutrophil cytoplasmic ab (ANCA),
- Scleroderma: anti-Scl-70, anticentromere, and anti-U1-RNP antibodies
what is the management for pulmonary hypertension
- Exercise and pulmonary rehabilitation
- Oxygen therapy - resting, exercise-induced, or nocturnal use
- Age appropriate vaccinations
- Smoking cessation (if applicable)
- Maintain healthy body weight
- Psychosocial support
- Birth control (non-estrogen) - PAH is associated with increased maternal and fetal risks, including high risk of death.
who do you refer patients with pulmonary hypertension to?
- Pulmonology or specialist in PH management
- Cardiology if WHO II
how do you classify severity of pulmonary hypertension
New York Heart Association System (NYHA)
what are the classes of the NYHA system
- NYHA I: No symptoms, no limitation of activity
- NYHA II: Slight limitation of activity. symptoms with ordinary activity
- NYHA III: Marked limitation of activity. Symptoms with less than ordinary activity
- NYHA IV: Unable to perform any activity without symptoms. Evidence of right heart failure. Dyspnea and fatigue at rest that worsens on exertion
- NYHA Symptoms: dyspnea, fatigue, chest pain, or near syncope with exertion.
what are the 2 main steps of management for pulm hypertension
- treat any underlying condition
- WHOII - treat left sided HF
- WHOIII - treat lung disease/hypoxia - is there vasoreactive disease?
- yes = CCB used for NYHA class I-III (high dose diltiazem and nifedipine MC)
- no = Based upon NYHA Classification, Only WHO PH classifications 1 and 4 have FDA approved pharmacotherapeutics for PH
what are the endothelin receptor antagonists
- oral - “entan’s”
- ambrisentan, bosentan, macitentan
what are the MOA of endothelin receptor antagonists
- MOA: reduces endothelin release leading to vasodilation
- Endothelin is produced in the cells that line the heart and lungs; when released results in vasoconstriction
what are the phosphodiesterase 5 inhibitors
- sidenafil
- tadalafil
what is the MOA of phosphodiesterase 5 inhibitors
- MOA: inhibition of PDE5 leads to vasodilation
- PDE5 is abundantly expressed in the lungs and causes vasoconstriction
what are the soluble guanylate cyclase stimulators
- riociguat (PO)
what is the goal of soluble guanylate cyclase stimulator therapy
Goal with this therapy is to improve exercise ability and NYHA functional class
what is the MOA soluble guanylate cyclase stimulator
- MOA: stimulates the activity of guanylate cyclase
- Guanylate cyclase produces cyclic guanosine monophosphate (cyclic GMP) in the lungs as a response to nitric oxide. Cyclic GMP causes the arteries to relax and widen (vasodilation).
What are the prostanoid agents
- epoprostenol (continuous IV pump)
- treprostinil (PO, inhaled, IV)
- iloprost (inahled)
what is the MOA of prostanoid agents
MOA: potent pulmonary vasodilation by acting on prostaglandin receptors with an additional benefit of inhibiting platelet aggregation
what are the prostacyclin receptor agonists
- selexipag (IV and PO, IV only short term)
What is the MOA of prostacyclin receptor agonsits
- MOA: attaches to and activates prostacyclin receptors in the lung resulting in vasodilation
- More selective for the prostacyclin receptor than the prostanoid agents.
what is the management for non-vasoreactive NYHA stage I pulmonary HTN
consider monotherapy
what is the management for non-vasoreactive NYHA stage II/III pulmonary HTN
- Combination therapy
- Endothelin antagonists and PDE5 inhibitors is often used initially
- Add on guanylate cyclase stimulators or oral prostacyclin receptor agonists if uncontrolled
what is the management for non-vasoreactive NYHA stage IV pulmonary HTN
Add on parenteral prostanoid to oral combination therapy
what is additional management for pulmonary hypertension
- Long-term anticoagulant therapy indicated for WHO Group 4 (some WHO 1) - warfarin, dabigatran, rivaroxaban, apixaban
- Thromboendarterectomy is recommended if no response to pharmacologic therapies in WHO Group 4
- Diuretics for symptomatic right sided heart failure
- Lung transplant reserved for those unresponsive to medical management (double preferred but single can be effective)
Another lecture down! doggo pic flip!
