Problem questions (ie ones I can't remember) Flashcards
Characteristics of the Parietal Pleura
Consists of a single layer of flat, cuboidal mesothelial cells, supported by loose connective tissue.
The arterial supply = intercostal and internal mammary arteries.
Venous blood drains to the systemic circulation.
Innervation = sensory branches of the intercostal and phrenic nerves.
Has direct connection to the lymphatic vessels.
- Stomas: increase with inspiration
Anterior parietal pleura drains to the internal intercostal lymph nodes
Posterior parietal pleura drains to the lymph nodes located along the internal thoracic artery.
Characteristics of the Visceral Pleura
Tightly adherent to lung surface and interlobar fissures
Microvilli, are evident on the apical surfaces - homeostasis of the pleural fluid and contribute to transmembrane solute and fluid movement.
Vesicles trap particles and glycoproteins, thereby reducing friction between the visceral and parietal pleurae.
Arterial supply = the bronchial arteries, with a minor contribution from the pulmonary circulation.
The lymphatic glands drain to the mediastinal nodes, following the course set by the pulmonary veins and arteries.
The visceral pleura has no sensory innervation, but it is supplied by branches of the vagus and sympathetic trunks.
Blood supply to the lung?
Lung gets blood from 2 separate systems:
1) Bronchial
○ High pressure/low volume
○ Bronchial arteries come form aorta or a branch from that
○ Provides blood to conducting airways -> mainstem bronchi to terminal bronchioles
○ Bleeding -> profuse, can result in massive hemoptysis
2) Pulmonary ○ Low pressure/high capacitance ○ Comes from RV ○ Supplies acinar units (gas exchange) ○ Alveolar hemorrhage -> low grade, chronic, diffuse
2 pathways for pulmonary fluid clearance
1) Lymphatics (most important)
2) Venular end of the microvascular bed
Causes of pulmonary hemorrhage in children
Infection Abscess Pneumonia Trauma Vascular disorders Coagulopathy Congenital Lung Malformations Miscellaneous: Catamenial, Factitious, Malignancy DAH syndromes
Causes of DAH syndromes
1) Immune mediated
- Idiopathic pulmonary capillaritis
- GPA
- MPA
- Anti-GBM disease
- SLE
- HSP
- Behcets
- Cryoglobulinemia vasculitis
- JIA
- COPA syndrome
2) Non-immune mediated
- IPH
- Acute idiopathic pulmonary hemorrhage of infancy
- Heiner’s syndrome
- Asphyxiation/abuse
- CV causes
- Pulm vein atresia/stenosis
- TAPVR
- Mitral stenosis
- Left sided failure
- PCH
- Pulm telangiectasia
6 classes of CF mutations
Class I: protein synthesis defect - affects CFTR transcription
Class II: maturation defect - misfolded protein, early degradatiob
Class III: gating defect - reduced ATP binding, resulting in abnormal gating characterized by a reduced open probability
Class IV: conductance defect-alter the channel conductance by impeding the ion conduction pore, leading to a reduced unitary conductance
Class V: reduced quantity- reduced amount of normal functioning protein
Class VI: Reduced stability - conformational stability reduced
Pseudomonas mechanisms of inhibition of lung defenses
1) Induced damage in immune cells
2) Virulence traits and secretion of virulence factors
3) Epithelial injury - loss of alveolar barrier - biofilm formation
4) resistant to neutrophils
Pseudomonas biofilm properties
1) Mucous provides anaerobic environment for bacterial growth
2) Decreased secretion of bactericidal compounds into CF airways
3) increased DNA and actin
Pseudomonas mechanisms of resistance
1) Amp C beta-lactamase
2) Extended spectrum beta-lactamase
3) Downregulation of Opr-D
4) Multidrug efflux pumps
5) Biofilm formation
Measurement of nasal potential difference
- Difference of electric potential measured between a reference electrode and silver/silver chloride electrode
- Inferior turbinate
- Recordings - continuous flow of salt solutions
- Measured in: saline, amiloride, chloride free amiloride, isoproteronol added to activate CFTR
- Sum = index of CFTR function
- <40 = abnormal ( 2 separate days)
Components of MAC complex
- M. Avium
- M. Intracellulare
- M. Chimaera
- M. Kansasii
“slow growers”
Treatment of MAC complex
1) No CF or cavitations: macrolide, rifampin, ethambutol 3x/week PO
2) CF: daily as above
3) CF with resistance or cavitations: 1-3 mos IV amikacin plus above
Treatment of M. Kansasii
**Think of TB
Isoniazid, Rifampin, Ethambutol x 12 mos after 1st culture negative
Components of M. Abscessus species complex
- M. Abscessus
- M. Massiliense
- M. Balleti
“rapid growers” *Younger and more severe disease
Treatment of M. Abscessus
Intensive and Continuation
I = 3-12 weeks of IV Amikacin + 1 of: Cefoxitin, Imipenum, Tigecycline
C = Inhaled Amikacin with 2-3 of: Moxifloxacin, Minocycline, Clofazamine, Linezolid
Dx criteria for NTM disease
Clinical (both are required):
- Pulmonary symptoms, nodular or cavitary opacities on CXR or CT showing multifocal bronchiectasis with multiple small nodules
- Appropriate exclusion of other diagnoses
Micro criteria (need one)
- Positive culture results from at least 2 separate expectorated sputum samples
- Postive culture results from at least one bronchial wash or lavage
- Transbronchial or other lung bx with mycobacterial histopath features and postive cx for NTM
General treatment guidelines for NTM pulmonary disease
1) Treat 12 mos beyond culture conversion (after first negative culture, need 3 negative in total)
2) No macrolide monotherapy
3) Monthly AFB smears + cultures while on treatment
4) Should show clinical improvement in 3-6 mos
5) Treatment failure = no response after 6 mos of appropriate treatment or no conversion to AFB negative culture after 12 mos
Conditions that may be associated with an increase incidence of CFTR mutations but insufficient evidence to fulfill a CF diagnosis
- Pancreatitis: acute or recurrent
- Disseminated bronchiectasis
- Isolated obstructive azoospermia
- ABPA
- Diffuse panbronchiolitis
- Sclerosing cholangitis
- Neonatal hypertrypsinogenemia
- Rhinosinusitis
- Heat exhaustion
Minimum criteria for ABPA (6)
1) Asthma or CF
2) Worsening lung function without another etiology
3) + skin prick with Aspergillus
4) IgE ≥ 1000
5) Increased Aspergillus species specific IgE and IgG
6) New or recent abnormal CXR or CT findings not improved with abx or physio
Additional criteria for ABPA (4)
1) Increased blood eosinophilia ≥ 400 when not on steroids
2) Aspergillus species -specific precipitating antibodies
3) Central bronchiectasis (central varicose)
4) Aspergillus species-specific containing mucous plugs
Characteristics of congenital bilateral absence of vas deferens (CFTR-RD)
1) Absence of palpable vas deferens
2) normal or increased FSH
3) Absence of intra-abdominal tract of VD and hypoplasia of seminal vesicles
4) pH <7.2, negative fructose + alpha 1-4 glucosidase
5) no developmental anomaly
How does intestinal current measurement work to assess CFTR function?
- record transepithelial short-circuit current or transepithelial voltage in rectal biopsies as measure of ion transport after stim with chloride secretagogues
- stimulates potassium channels - increasing driving force for luminal chloride
- in CF - activation fails to induce apical chloride secretion and results in inverse response
+ response = potassium secretion with no chloride
Assessment of Pancreatic Function
Pancreatic fxn should be objective assessed at time of diagnosis
Pts who are PS should be monitored regularly for evidence of progression ot PI
Function can be assessed several ways:
- 72h fecal fat collection (+record fat intake)
- PI defined by fat loss >15% of intake in infants <6 mos; >7% of intake in older infants - serum trypsinogen
- at birth serum levels usually elevated, then decline to low-undetectable leves in PI pts by age 5-7
- PS pts show fluctuating levels w/I and above N range at all ages
- in pts who are PS at diagnosis and progress to PI, there’s a delayed decline in serum trypsinogen - fecal elastase -low in pts with PI
Pulmonary complications of IBD
Bronchiectasis (most common) Tracheal stenosis Ileobronchial colobronchial fistula COP (Cryptogenic organizing pneumonia) granulomatous and necrobiotic nodules ILD Pulmonary Vasculitis Drug induced disease (Sulfasalazine and Mesalamine can cause HP) Opportunistic infection Malignancy Pulmonary thromboembolism
Major criteria for HP (6)
Need 4
- Symptoms compatible with HP
- Evidence of exposure to antigen
- Radiographic characteristics consistent with HP
- BAL fluid lymphocytosis (CD8 > CD4)
- Lung biopsy demonstrates histology consistent with HP
- Positive natural challenge that produces symptoms and objective abnormalities after reexposure to the offending antigen
Pathology findings in sub-acute hypersensitivity pneumonitis
The classic triad of
- Interstitial lymphocytic-histiocytic cell infiltrate.
- Bronchiolitis obliterans.
- Scattered poorly formed non-necrotizing granulomas
Pathology findings in chronic hypersensitivity pneumonitis
- Giant cells, granulomas, or Schaumann bodies
- Interstitial pneumonia (UIP)–like Pattern.
- A nonspecific interstitial pneumonia (NSIP)–like pattern or a bronchiolitis obliterans organizing pneumonia like disease can also be seen in chronic HP
Pathology findings in acute hypersensitivity pneumonitis
- Interstitial mononuclear cell infiltrate.
2. Granulomas and macrophages with foamy cytoplasm have also been reported.
Causes of central bronchiectasis
- ABPA
- Congenital tracheobronchomegaly
- CF
- Williams Campbell syndrome
Causes of upper lobe predominant bronchiectasis
- CF
- TB (NTM can be middle too)
- ABPA (mid and upper)
- Chronic HP (mid, upper)
Causes of lower lobe predominant bronchiectasis
Most common location
- post infectious
- aspiration
- immunodeficiency
- PCD
- with BO post transplant
Pathology lesions characteristic of cryptogenic organizing pneumonia
Excessive proliferation of granulation tissue -> consists of loose collagen-embedded fibroblasts and myofibroblasts involving alveolar ducts + alveoli +/- bronchiolar intraluminal polyps
Treatment of cryptogenic organizing pneumonia
Steroids (IV or PO)
Macrolides
BAL findings in:
1) Sarcoidosis
2) LCH
3) Hypersensitivity pneumonitis
4) Pulmonary hemorrhage
5) Aspiration
1) Lymphocytosis (increased CD4:CD8 ratio)
2) no eosinophils, stain S-100, CD1a, langerin
3) Acute = neutrophilia, >48hrs = lymphocytosis, increased CD8
4) Gross blood, increasing with each sample
5) Lipid laden macrophages
2 pathology features of desquamative interstitial pneumonitis
Foamy alveolar macrophages
Type 2 alveolar cell hyperplasia
Components of the Starling equation
Qf = Kf[(Pc − Pis) − σ(πpl − πis)]
where Qf = net flow of fluid
Kf = capillary filtration coefficient; this describes the permeability characteristics of the membrane to fluids and the surface area of the alveolar-capillary barrier
Pc = capillary hydrostatic pressure
Pis = hydrostatic pressure of the interstitial fluid
σ = reflection coefficient; this describes the ability of the membrane to prevent extravasation of solute particles such as plasma proteins
πpl = colloid osmotic (oncotic) pressure of the plasma
πis = colloid osmotic pressure of the interstitial fluid
Note that the surface area of the alveolar-capillary barrier is included in the Kf.
The Starling equation is very useful in understanding the potential causes of pulmonary edema, even though only the plasma colloid osmotic pressure (πpl) can be measured clinically.
Five PARDS diagnostic criteria.
- Exclude patients with perinatal lung disease
- Within 7 days of known clinical insult
- Respiratory failure not fully explained by cardiac failure or fluid overload
- Chest imaging findings of new infiltrate(s) consistent with acute pulmonary parenchymal disease
- Oxygenation
CPAP ≥ 5, P/F ≤ 300, SpO2/FiO2 ≤ 264
Mild = 4 ≤ OI ≤8
Moderate = 8 ≤ OI ≤ 16
Severe = OI ≥ 16
