Non-infectious disorders (Raf) Flashcards
ECG finding in PH?
RVH
(Also: right atrial enlargement, RV strain)
- ECG cannot be used to rule out PH because it will be normal in mild PH
Physical exam findings in pulmonary hypertension?
Failure to thrive, clubbing RV heave (which is actually in the left parasternal region), loud P2 (pulmonic component of second heart sound), holosystolic murmur of tricuspid regurg Hepatomegaly, high JVP Pedal or sacral edema RV gallop
What is the mechanism of injury in drowning?
Key point: surfactant dysfunction
- Majority of drownings are wet drowning (with direct aspiration of fluid), in contrast to dry drowning, where there is laryngospasm
- For individuals who are dead on arrival, distinction between salt and freshwater is relevant. Presumably, they have aspirated enough ~15 mL/kg to die and have the mechanism of fluid shifts and electrolyte changes be relevant. (In this context, fresh water drowning is worse than a salt water drowning
- For individuals who are NOT dead on arrival, the distinction is not very important. Both types of aspiration cause:
- Deactivation of surfactant—>decreased lung compliance—>VQ mismatch and shunting—>hypoxemia
- Other mechanisms for lung injury:
- Neurogenic pulmonary edema - due to CNS hypoxemia
- Post obstructive pulmonary edema
- Secondary infection
- Altered pulmonary capillary permeability
- Reactive pulmonary oedema
What are the features of failing fontan and why do these complications develop?
Two ways a fontan patient can “fail”:
- single ventricle failure
- preserved systolic/diastolic function
Fluid doesn’t drain effectively into the fontan circulation so back up venous pressure
Many of the complications of failing fontan are due to increased lymph production, which can’t be effectively drained due to increased venous pressure.
Increased venous pressure (which I think occurs because passive flow from systemic venous to pulmonary veins is decreased/backing up fluid)–>result in increased production of lymphatic fluid + thoracic duct can’t drain into the vein b/c the venous pressure is high. –>accumulation of lymphatic fluid in various organs and increased back pressure–>chylothorax, plastic bronchitis, lymphangiectasia (secondary cause), protein losing enteropathy.
Retrograde flow from thoracic duct to lung parenchyma–>plastic bronchitis
Hepatic congestion (I’m not sure if lymphatic are related)
types of bronchial cases and diseases they are associated with?
Cast = obstructive airway plug. Can get big enough to fill branching pattern of tracheobronchial tree
Type 1: cellular, inflammatory, contains fibrin + inflammatory cells (mainly eosinophils). Seen in asthma, CF, acute chest syndrome in sickle cell disease
Type 2: acellular, non-inflammatory, contains mucin, fibrin, no inflammatory cells. this happens in Fontan patient, lymphatic abnormalities
Inheritance of PCD?
Autosomal recessive
Most common genetic defect for PCD?
ultrastructural defects are the most common (80% of patients).
Outer dynein arm defect is the most common. –this is a bit of simplified answer. Of the most common defects, 2 are outer dynein arm and 1 has normal ultrasturcutre,
What is the most comment genetic defect for PCD?
• DNAH5 - outer dynein arm
• DNAH11 - normal ultrastructure so TEM could be normal
• DNAI1 - outer dynein arm
Diseases due to sensory ciliopathy?
Polycystic kidney disease, Baredt-Biedl, Joubert, retinitis pigmentosa.
(It’s important to know these conditions since there isn’t a perfect separation between primary/sensory ciliopathies and PCD (which is a disorder of motile cilia). If seeing patients with these conditions, then keep the diagnosis of PCD at the back of your mind.
Recall that there 3 types of cilia: sensory, motile, nodal (embryonic)
Lung function abnormalities in pectus excavatum?
2/3 of patients have normal lung function with normal or low normal FVC/TLC
CPET and pectus excavatum?
- lower maximal stroke volume (O2 pulse)
- decreased VO2 max
- Decreased anaerobic threshold
- higher RR, lower tidal volume (I think they have some ventilatory limitation as well)
Effect of surgery for pectus excavatum on lung function and cardiac function?
- No clinically significant change in lung function. Studies have either very small improvements in EV1/FVC or no change or decrease
- That being said, there seems to be an improvement in exercise symptoms, which is due to improvements in cardiac function – improvements in stroke volume and VO2 max. Improvements in ECG abnormalities, which shows improvements in preoperative cardiac compression
How is severity of pectus excavatum measured?
The pectus severity index (PSI), also known as the Haller index → describes the depth of the pectus defect by comparing the ratio of the lateral diameter of the chest to the sternum-to-spine distance, at the point of maximal depression.
- The chest CT scan should be performed at full inspiration to maximize the intrathoracic dimensions and to provide standardization to permit comparison with subsequent scans.
- A normal chest has a PSI of ≤2.5.
- Among patients referred for surgery based on clinical criteria (ie, without consideration of CT scan results), all patients had a PSI of >3.25, whereas patients with PE who were not referred for surgery had PSI <3.25
- PSI>5 is associated with mild restriction
Indications for surgery pectus?
- exercise limitation
- poor self image
- above is from Kendig’s
- ideally late childhood, early adolescence
- Below if from uptodate, but the indications are not well standardized
As per uptodate, 2 or more of:
- PSI of >3.25 (measured on CT scan)
●Cardiac compression, displacement, mitral valve prolapse, murmurs, or conduction abnormalities
●Pulmonary function testing showing restrictive respiratory disease
●Failed previous repair of PE
(Cosmetic indiction can also be considerd)
CT findings of bronchiectasis?
- Elevated broncho-arterial ratio of >1-1.5, keeping in mind that normal ratio in children is about 0.8
- Lack of peripheral tapering of bronchi
- Tram track sign
- Signet ring sign
- Ancillary findings:
- Bronchial wall thickening
- Mucoid impaction
- Air trapping
CXR findings of bronchiectasis
- ring shadows (from appearance of bronchi end on)
- tram track opacities
- increase in bronchovascular markings
- air fluid level with cystic bronchiectasis
Advantages and disadvantages of low molecular weight heparin?
Advantage:
- long half life so not as frequent dosing, no need for close monitoring
Disadvantage:
- expense
- injection is required
- only partially reversible with vitamin K
- higher half life results in increased risk of bleeding
(I didn’t spend a long time verifying this answer from our study notes)
Advantages and disadvantages of warfarin?
Advantage:
- oral
- fully reversible with vitamin K
- once daily dosing
- low cost
Disadvantage:
- requires monitoring for INR
- narrow therapeutic window
- may interact with food and medication
- slow onset of action
What are the genetics for HHT?
Autosomal dominant, with variable penetrance
What are the clinical criteria for HHT? Are they reliable in children?
Curacoa criteria:
- Spontaneous and recurrent epistaxis
- First degree relative with HHT
- Mucocutaneous telangiectasia
- Visceral organ involvement: telangiectasia in GI tract or AVM in pulmonary, cerebral or hepatic
- 1 criteria: unlikely HHT
- 2 criteria: probable HHT
- 3 criteria: confirmed/definite HHT
These criteria are NOT very reliable in children, since most people don’t achieve a criteria diagnosis till age 40 years.
Criteria are helpful for ruling in, but not ruling out diagnosis.
(Technically you can make a diagnoses based on these criteria OR genetics)
What is the approach to genetic testing for first degree relatives with HHT? Eg. asymptomatic child of a parent/sibling with HHT.
This child has possible HHT (not based on Curacao, but just generally)
If the familial genetic mutation is known, then first degree relatives should be tested for that mutation. If the genetic mutation is not known, then first degree relative can be managed as if they have HHT with the same screening recommendations.
What are the genes implicated in HHT?
- ENG gene —>corresponds to HHT1
- ACVRL1 gene—>corresponds to HHT2
- SMAD4—>juvenile polyposis and HHT, so risk of GI malignancy
Screening Recommendations for HHT?
Seeing a new patient:
- clinical exam -look for orthodeoxia by assessing by supine and upright saturation
- investigate for anemia and iron deficiency (epistaxis)
Cerebral AVM: brain MRI at infancy and adulthood (eg. 18 years). No need to re-screen if these are negative.
Pulmonary AVM: screen with bubble echo at diagnosis and after puberty (makes sense to do before transition to adulthood since there can be growth of pulmonary AVM during teenage yearS). (BTS guideline actually does not recommend rescreening for adults) If echo positive then CT. (Of note, the BTS 2017 guideline prefers CT chest +/- contrast as the preferred screening test. There has to be very good local expertise to rely on bubble echo). (Of note, normal CXR, oxygen saturations and lack of symptoms is NOT enough to exclude a pulmonary AVM)
Hepatic AVM: no routine screening
If a patient has the SMAD4 mutation, then they should be referred to GI for polyposis and GI malignancy screening, with colonoscopy starting at 15-18 years.
How do you counsel patients with pulmonary AVM?
- Antibiotic prophylaxis for procedures with risk of bacteremia (since many cases of cerebral abscess happen in this context
- Intravenous access—>extra care to avoid intravenous air
- Avoidance of scuba diving
Unusual systemic disorders associated with pulmonary hypertension?
HHT, in particular hepatic AVM are associated with pulmonary hypertension
Sickle cell
CCHS
For an individual with symptoms of HHT, but no family history, could they still have HHT?
Yes, they could have a de novo mutation
Long-term Management of epistaxis in patient with HHT?
- Nasal lubricant
- Endonasal coagulation is the first line procedure
- Later procedures: Young’s procedure, septal dermoplasty
- In general, you want an ENT with expertise in HHT
What is the criteria for embolization of a pulmonary AVM in an asymptomatic patient?
- All patients with PAVM should be referred to interventional for an evaluation.
- embolization should be considered even in asymptomatic patients b/c there are benefits like decreased risk of stroke
- if the shunt is only visible on echo, then there is lower risk with procedure
- if the shunt is radiologically visible, there is no 3 mm rule
- Above is from BTS 2017 pulmonary AVM guideline
2009 guideline: symptomatic, feeding vessel diameter of >=3 mm
What are the complications of pulmonary AVM?
Cerebral abscess Embolic Stroke Ischemic stroke TIA Pulmonary hemorrhage Hypoxemia
Physical exam findings for HHT
- Vitals: saturation, orthodeoxia in supine and upright position
- Epistaxis–>endonasal telangiectasia
- Retinal telangiectasia and hemorrhage
- Telangiectasia on lips, oral mucosa, finger tips. Can use a hand held illuminator to look for vascular anomalies on digits
- Resp: thoracic bruit is heard in ½ of HHT patients with cyanosis (Emedicine), clubbing (association between cyanosis and clubbing with cerebral abscess and stroke)
- CNS: Bruit if cererbrovascular malformation and open fontanelle ?
· GI:
· High-output heart failure
· Hepatomegaly
· Portal hypertension
· Encephalopathy
· Right-upper-quadrant pain and jaundice
Definition of PH, PAH and post capillary pulmonary hypertension?
PH = mPAP >20 mmHg, in patient >3 months of age at sea level
Precapillary = pulmonary arterial hypertension:
- mPAP>20 mmHg
- Pulmonary artery wedge pressure or LVEDP <=15 mmg
- PVRi >= 3 WU (woods units)
Post capillary PH:
- mPAP >20 mmHg
- PAWP or LVEDP >15 mmHg
- Isolated post capillary if PVRI<3 woods unit and DPG <7 mmHg
Pre and post capillary: PVRI >=3 WU and DPG >=7
DPG: Diastolic pulmonary gradient (DPG) is a novel hemodynamic marker that is calculated as the difference between pulmonary artery diastolic pressure (PADP), and mean pulmonary capillary wedge pressure (PCWP)
(when assessing patients with left sided cardiac disease for heart transplant, you have to figure out if they just have post capillary PH or if there is also precapillary PH. Longstanding left sided cardiac disease will cause pre-capillary PH. If these patients have significant pulmonary hypertension, then they would need heart lung transplant.
Mechanisms of PCD?
Ultrastructural defect:
- dynein arm defect
- radial spoke defect
- microtubular transposition defect
Functional defect - ineffective beat in spite of normal ultrastructure
Causes of an elevated D dimer?
- Pulmonary embolus (this is often why the test is sent off, though the test has low specificity)
- D dimer is positive when there is inflammation or coagulation
- DIC
- Inflammation: trauma, surgery, infection: pneumonia, malignancy, inflammatory like kawasaki disease and JIA
Risk factors for pulmonary embolism in a teenager?
- Teenage girl: OCP, pregnancy
- Drugs: IV drug use, in particular injection into femoral veins
- Antiphospholipid antibody syndrome
- Inherited thrombophilia: factor V Leidein, Prothrombin gene mutation, protein C or S deficiency, antithrombin deficiency
- Major surgery such as orthopedic
- Malignancy
- Major trauma
- Immobilization due to recent air travel
(on a side note, antiphospholipid syndrome is a hypercoagulable condition, which may or may not be associated with lupus, antibodies: lupus anticoagulant, anticardiolipin, antibeta2glycoprotein)
Differential diagnosis for bronchiectasis?
See chapter 26 evernote scheme
Main categories:
- post infectious, post TB, post BO
- immunodeficiency
- CF, PCD
- aspiration
- Obstructive: foreign body. Obstructive airway lesion with TB, lymphadenopathy
- ABPA
- alpha 1 antitrypsin
- ILD such as pulmonary fibrosis
- Congenital: munier kuhn, william campbell
Minimum investigations for bronchiectasis?
- CBC
- IgA, M, G, E
- Vaccine response
- Sweat chloride
- Sputum culture for routine and mycobacterial culture
- CXR and CT during clinically stable disease
Draw the ultrastructure of a cilia?
(They will likely specify motor cilia (which line the respiratory epithelium), as opposed to primary/sensory cilia (which are non-motile) and nodal cilia (which are present in the embyro). These other cilia have a different structure.
Key points:
- 9+2 arrangement
- 9 doublet of microtubules surrounding a central pair of singlet microtubules
- Within the doublet, there is the A microtubule (left) and the B microtubule (on the right). The outer and inner dynein arms are attached to the A microtubule.
- There is a sheath surrounding the central pair of microtubules
- Radial spoke connects the doublets to the central sheath
- Nexin protein connects the doublets to each other
- Plasma membrane surrounds the whole structure
Describe the pathways involved in pulmonary hypertension?
Three pathways:
- Prostacylin pathway:
- Arachidonic acid can undergo two pathways of conversion. One pathway leads to prostacyclin (PGI2). The other pathways leads to production of thromboxane A2. PGI2 causes smooth muscle relaxation and inhibits platelet aggregation. Thromboxane A2 has the opposite effect and causes smooth muscle constriction and platelet aggregation. Treatment for PH: prostacylin derivative. PGI2 mediates it’s effects through production of cAMP.
- Eg. epoprostenol is a prostacylin analogue
- Nitric oxide pathway: L-arginine is converted to L-citrulline via eNOS (endogenous NO synthetase). this also produces NO, which stimulates guanylate cyclase to produce cGMP from GTP. cGMP causes vasodilation and anti-proliferation. Phosphodiesterase-5 degrades cGMP. So can use a PDE-5 inhibitor.
- Eg. sildenafil is a phosphodiesterase inhibitor
- Endothelin pathway: endothelin acts on endothelin A and B receptors to cause vasoconstriction. So you want to have an endothelin receptor antagonist.
- Eg. bosentan is an endothelin receptor antagonist
Name one genetic mutation involved in PAH and it’s inheritance?
BMPR2 = bone morphogenic protein receptor 2. It is autosomal dominant, but has variable penetrance
Patient with sickle cell disease who has a vaso-occlusive crisis, but not acute chest syndrome. What would be reasons for hypoxemia?
- Hypoventilation: depression of respiratory rate due to narcotics because of pain; nocturnal hypoventilation due to OSA
- Diffusion barrier: sickle cell chronic lung disease, pulmonary hypertension
- V/Q mismatch due to atelectasis from splinting. Increased frequency of wheezing and obstructive lung disease (which may or may not be asthma) may contribute to VQ mismatch.
Patient on BP lower medication who has a cough. Which medication?
Ace inhibitor
- ARB is less likely to cause cough
- ACEi cough starts within 1-2 weeks of starting ACEi
- Cough gets better after stopping ACEi, often within 1-4 days (But can take up to 4 weeks)
How is a large pneumothorax defined and why is this definition important?
- Size is defined by measurement of the interpleural distance
Distance from lateral edge to apical dome of lung > 3 cm OR
distance from lateral edge to lung at level of hila >2 cm (BTS) on an upright CXR
If pneumothorax is large, then intervention such as needle aspiration or insertion of chest tube (no consensus on which of these upfront)
For smaller pneumothoraxes that don’t meet this threshold–>100% oxygen, but no need for insertion of a drain
If tension pneumo–>needle thoracentesis
For a patient with pneuthorax with chest tube inserted, what level of suction should be applied?
NO suction upfront since there can be re-expansion pulmonary edema and persistent air leak. If no improvement at 48 hours, then apply suction at -10 or -20
For patient presenting with primary spontaneous pneumothorax, is CT indicated?
No, because even if you find blebs, it’s unclear what the next step would be for management.
Since we don’t know which patients are the ones who will have recurrent pneumothoraxes, we have to wait till they recurrently present and identify themselves in order to offer pleurodesis
When can patients with pneumothorax fly or dive?
Flight: CXR resolution of pneumothorax + an additional 7 days since there is a risk of re-expansion of the air under lower barometric pressure
Diving: very restrictive guidelines around diving–>definitive surgical management (eg. bilateral pleurectomy) + normal lung function + normal CT. (Pulmonary barotrauma is one of the major causes of death in divers. Lung is compressed on the descent–>pulmonary edema, pulmonary hemorrhage. On the ascent–>alveolar rupture, pneumothorax, pneumomediastinum)
In a patient with pneumothorax and chest tube, how is persistent air leak defined? Differential and management?
Persistent air leak: >3-7 days of bubbling.
- Persistent bubbling is either from the patient or the tubing system
1. System leak - chest tube, drainage tube, connections, pleurivac system
2. Bronchopleural fistula - Clamp the tube close to the patient. If bubbling is still happening, then it’s coming from the tubing system. You can identify the location of bubbling by re-clamping and finding out where the bubbling stops
Medications for managing oral secretions and their side effects?
- Anticholinergics: transdermal scoplomaine, oral atropine or glycopyrrlate
- Surgical: salivary ligation or removal, botox injection
Anticholinergic side effect:
- They can have significant side effects
- Dry mouth and thickening of oral secretions–>be cautious in patients with small tracheostomy tube and neuromuscular disease (limited ability to cough up secretions)
- Urinary retention, constipation, flushing, behavioural change
- nasal congestion, nausea, vomiting, photophobia
Botulinum toxin:
- pain, difficulty chewing, dysphagia, speech difficulty, dry mouth
What is the preferred diagnostic test for pulmonary embolism?
CT-pulmonary angiography. If this is not available or if the results is inconclusive, then do VQ scan
What is the role of D-dimer in diagnosing PE in children?
- Role of D dimer in children is not clear
- Diagnostic tools like Wells score and Geneva score have been designed for adults and are not validated in children
- Some studies suggest that in children with low index of suscpicion for PE, negative D dimer can safely exclude PE. If the D dimer is positive, then need to proceed to CT
- Important to note that if there is a high index of suspicion for PE, then don’t bother with D dimer and go straight to CTA
Why does tension pneumo develop and what are physical exam findings?
- Ball valve phenomenon –>air enters the pleural space (either through defect in lung/visceral pleura or through chest wall/parietal pleura) on inspiration. On expiration–>valve like opening closes and this prevents drainage of pleural air
Physical exam findings: decreased breath sounds on affected side, hyper-resonance, tachycardia, hyopotention, tachypnea, mediastinal shift with tracheal deviation
Oncology patient who is receiving chemotherapy. They have fever, diffuse infiltrates, hypoxemia. Differential diagnosis?
Broad differential:
- Vascular: pulmonary hemorrhage - can get DAH as an early complication post HSCT. Thromboembolic (patients with malignancy has higher change of clot)
- Infection: high on the differential since they are immunocompromised.
- Inflammatory/Toxin: drug toxicity, radiation pneumonitis –>watch out for pneumotoxic drugs, especially if there is impaired kidney function. What does of radiation did they receive? (it will be hard to prove drug or radiation as being a cause for their presentation, unless you’ve rule out other things like infection; as well there is a variety for radiographic and histologic findings, nothing pathognomonic). Factors can work together synergistically so being on pneumotoxic drugs + radiation can cause lung injury.
- Autoimmune - less likely in this context
- Neoplastic - maybe progression of underlying malignancy
Practically:
- probably would do CT and bronch to get a better sense. Are there pathognomonic findings on CT like nodules, which might suggest fungal infection? Bronchoscopy to look for infection, hemorrhage…
Older patient (>2 years of age) with ILD symptoms (non-productive cough, dyspnea, poor activity tolerance)
Differential:
- Vascular: diffuse alveolar hemorrhage
- Infection - if immunocompromised–>chronic infection
- Bronchiolitis obliterans - related to post-infectious, rejection or GVHD
- aspiration
- ongoing disorder of infancy - NEHI, surfactant deficiency
- Inflammatory:
- systemic inflammatory disease - eg. lupus, scleroderma, sarcoid
- toxic exposures: pneumotoxic drugs, radiation, inhalational exposures
- autoimmune pulmonary alveolar proteinosis
- other: eosinophilic pneumonia, hypersensitivity pneumonitis, organizing pneumonia
complications of radiation therapy?
- acute pneumonitis (within 3 months of radiation)
- chronic radiation fibrosis (within 6-12 months of radiation)
- cryptogenic orgnanizing pneumonia
- impaired chest wall growth
risk factors for radiation induced lung injury?
- dose of radiation: >10 Grey units (mean lung dose)
- age of patient
- induction chemotherapy or concurrent chemotherapy - eg. bleomycin
- radiation recall (in a patient who received prior radiation therapy, giving chemotherapy can cause delayed radiation injury)
- younger age at radiation
Common organisms in CGD?
- Cadida
- Aspergillus**
- Nocardia
- Pseudomonas, PJP
- Listeria
- Burkholderia cepacia
- E. coli
- Staph aureus**
- Serratia
- H. pylori
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