Respiratory pathophys. part 2 Flashcards
risk factors for asthma
Host factors: genetic, gender (F), obesity
Environmental factors: allergens, occupational sensitizers, tobacco smoke, air pollution, respiratory infections (RSV), diet (low Vit. D)
asthma (defn)
chronic inflammatory disorder of the airways,
(typically eosinophilic inflamm)
–> recurrent episodes of wheezing, chest tightness, cough,
*usually reversible, BUT can get remodeling(!)
Th1 vs. Th2 asthma phenotype
Th1: get Sx young, but go away (rural, have siblings, go to daycare, etc)
Th2: get asthma older & it stays (urban, more antibiotics, less trigger exposure when young)
Major cell types involved in asthma
Inflammatory: Eosinophils, mast cells, Th2
Structural: epithelial, sm. muscle, and endothelial, etc.
low V/Q vs. shunt
Low V/Q: decreased ventilation to that alveolus, but may be normal elsewhere. CAN correct PCO2 AND PO2 with adding O2.
Shunt: completely blocked ventilation to that alveolus, but may be normal elsewhere. CanNOT correct PO2 (but can PCO2) with adding O2.
Acute Respiratory Distress Syndrome
- Acute (within 7 days)
- bilateral infiltrates on CXR
- infiltrates not fully explained by heart failure of fluid overload
- hypoxia (use PaO2/FiO2 to rate severity)
Pathogenesis of pneumonia (4 types)
- pneumonia = infection of lung tissue
1. aspiration (most common cause)
2. aerosol
3. hematogenous
4. reactivation
Aspiration pneumonia
something goes down wrong way & causes infection;
- requires abnormal host or abnormal flora **
from:
- requires abnormal host or abnormal flora **
- oropharyngeal secretions (#1)
- stomach contents
- foreign body
respiratory characteristics of abnormal host:
- Impaired airway/mucociliary clearance
- poor cough: COPD, EtOH, neuro disease, lung cancer;
- bad cilia: kartagener’s, immotile cilia syndrome, viral inf, CF - medications
- - antipsychotics, antacids, inhaled corticosteroids
most common bacteria causing pneumonia (5)
(for community-acquired pneumonia)
- S. pneumonia - H. influenzae
- S. aureus - Mycoplasma
- legionella *aerobic gram neg. bacteria
Diagnosis of pneumonia
1: abnormal CXR (esp. compared to previous x-ray for that person) ** help distinguish from bronchitis **
- or CT scan
- Use history to understand exposures!
- Antigen tests (pneumococcus, influenza, legionella)
- Culture sputum, etc – only if likely severe, should not delay antibiotic start
- Use history to understand exposures!
Empiric therapy for pneumonia in OUTpatients
Low resistance risk: macrolide (antibiotic)
High resistance risk: macrolide + beta lactam or fluoroquinolone, for 5+ days
Empiric pneumonia therapy in Inpatients or non-Psuedomonas ICU
Inpt: Fluoroquinolone OR beta lactam + macrolide
ICU: beta lactam + macrolide or fluoroquinolone
Empiric therapy in ICU pts w/ possible pseudomonas
Anti-pseudomonal + ciprofloxacin
- be wary of other causes of pneumonia-like Sxs!!!
- -> take step back and reassess if not getting better!
Virchow’s triad
=> increase risk for thrombus formation: (can lead to PE)
- venous stasis
- endothelial damage
- hypercoagulability
imaging used to prove DVT
- venography (w/ contrast, CT)
- doppler ultrasound
Imaging used to prove Pulmonary Embolism
- pulmonary angiography (w/ contrast)
- ventilation-perfusion lung scan
- CT angiography
- MRI
- Need clinical insight (Hx, etc) along w/ imaging to make Dx**
Common sources for emboli (sites)
(usually Deep Vein Thrombosis - DVT)
- External iliac v.
- superficial femoral v.
- deep femoral v.
- popliteal v.
- posterior tibial v.
Westermark’s Sign
Xray finding indicating pulmonary embolism;
= localized oligemia w/ proximal pulmonary artery enlargement.
(rare, but classic if seen)
Hampton’s Hump
Xray finding indicative of pulmonary embolism,
= localized pleural triangular density.
–> = visualization of infarcted tissue from PE.
(rare, but classic if seen)
type of effusion found w/ pulmonary embolism
not always w/ PE, but if so, will be:
small, hemorrhagic exudative effusion.
typical ABG (blood gas) levels in Pulmonary Embolism
- hyperventilation
- low PaCO2
- PaO2 normal OR low
(WARNING: can have 100% normal ABG w/ PE!)
Utility of V/Q scan in diagnosing PE
normal V/Q scan EXCLUDES pulmonary embolism;
abnormal is not diagnostic (not specific).
Utility of D-dimer test in diagnosing pulmonary embolism
if low clinical suspicion of PE: normal D-dimer excludes PE;
otherwise not specific/diagnostic
Common ECG findings w/ pulmonary embolism
- R ventricular dilation & hypokinesis
- Intraventricular septal shift (bulges away from RV)
(3. “clots en passage” = clots sitting in heart RA, waiting to travel to lungs)
Therapies for pulmonary embolism (what, why, when)
1. Anti-coagulation (Heparin 1st, then warfarin/indraparinux)
*start empirically! 2. Thrombolysis (tPA or urokinase) - esp. if hypotensive or hemodynamically unstable, BUT has risk of intracranial hemorrhage! 3. Surgical thrombectomy or umbrella - if contraindication to anti-coag, or recurrence on anti-coag.
Main strategies for prevention of pulmonary embolisms
#1: Early ambulation after surgery/hospitalization 2. prophylactic anti-coagulation if moderate risk (ie: after surgery)
Bronchiectasis
Chronic dilation of bronchi/bronchioles, with airway wall thickening from inflammation or obstruction.
Sx: chronic cough, excess sputum, recurrent chest infections, malaise
Dx: chest CT, obstructive PFT
Definition of pulmonary hypertension
mean pulmonary artery pressure > 25 mmHg at rest.
2 parts of lung circulation
(dual vasculature)
- Bronchial circulation (from aorta)
- Pressure: systemic; Compliance: low
- Pulmonary circulation (from pulmonary a.)
- Pressure: low; Compliance: high
* minimal change in pressures w/ exercise*
- Pressure: low; Compliance: high
pathological changes w/ pulmonary hypertension
- affected pulmonary arteries thicken & constrict
- UNaffected pulmonary arteries dilate bc increased BF
- R ventricle dilates & hypertrophies (bc increased pressure)
5 official types of pulmonary hypertension
- Pulmonary artery hypertension
- pulm. htn secondary to L heart disease
- pulm htn secondary to lung disease/hypoxia
- Chronic thromboembolic pulmonary htn
- pulm htn “w/ unclear multi-factorial mechanisms” (idiopathic)
Interstitial lung disease (defn)
non-infectious, non-malignant process in the lower respiratory tract causing stiffness and fibrosis.
* in an immunocompetent individual.
Main pathophysiologic aspects of interstitial lung disease (4)
- decreased lung compliance (stiffer, more work of breathing)
- decreased lung volumes, but FEV1/FVC > 80% preserved
- diffusion impairment (small lungs = decreased surface area)
- low DLCO
- Impaired gas exchange
- V/Q mismatch & hypoxemia even w/ minimal activity
- pulmonary HTN (“cor pulmonale”)
clinical signs of interstitial lung disease
Hx: gradual/insidious dyspnea, dry non-productive cough
Physical exam: lung crackles, finger clubbing, edema & cor pulmonale
occupational & environmental causes of interstitial lung disease
aka: pneumoconiosis
- INorganic: asbestosis, silicosis, coal worker’s lung, talc pneumoconiasis, etc.
- ORganic: aka farmer’s lung/allergic extrinsic alveolitis
3 categories that cause bronchiectasis
- Cystic fibrosis
- non-CF (infection, etc.)
- traction bronchitis (usually w/ interstitial lung disease)
pathogenesis of bronchiectasis
- airway injury –> impair cilia & host defense (immune-mediated)
=> airway obstruction (=> scooped exp. limb on PFT) - irreversible airway inflation –> inflammation, mucosal edema, ulceration…
=> recurrent infectious flares (ie: pseudomonas aeruginosa)
pathogenesis of Cystic Fibrosis
(mutations in CF gene - encodes chloride channel, which regulates other ion channels)
Ion transport abnormalities –> impaired mucus secretion, poor mucociliary clearance.
common non-ciliary causes of bronchiectasis
- Hx of infection: w/ pneumonia, mycobacteria
- allergic bronchopulmonary aspergillosis
- immunodeficiency/autoimmune disease
- inhalational injury
techniques for diagnosis of Cystic Fibrosis
1: Gibson-Cooke sweat test (high [ ] Cl in sweat, trigger w/ pilocarpine)
- Genotyping
- Newborn screen
primary ciliary dyskinesia
autosomal recessive inherited disorder,
= abnormalities is cilia structure that make them in immobile;
–> chronic sinusitis, bronchiectasis, infertility.
*often w/ Kartagener’s syndrome -> also situs inversus.
clinical findings w/ pulmonary hypertension
- Hx: Dyspnea, fatigue
- Lungs: clear
- Heart: prominent P2, RV hypertrophy, R heart failure,
- Liver, etc: ascites, peripheral edema
(Histo: intimal fibrosis, smooth m cell hypertrophy)
Causes of pulmonary artery hypertension (type I)
- idiopathic
- heritable
- drug-induced
Risk factors: collagen vascular disease, congenital heart disease, cirrhosis/portal HTN
changes from endothelial dysfunction for w/ pulmonary HTN
- decreased NO/cGMP signaling - vasodilation
- decreased prostacyclin/cAMP signaling - vasodilation
- increased endothelin signaling –> vasoconstriction & smooth muscle cell proliferation.
most common type of pulmonary hypertension (in world)
L heart disease (L systolic OR diastolic dysfunction, valve disease)
–> increase peripheral vascular resistance & L atrial P
Causes of Type III pulmonary HTN
(from hypoxia or lung disease)
- alveolar hypoxia (COPD, etc.)
- impaired breathing control (ie: sleep apnea)
- living at high altitude
common causes of Type V pulmonary HTN (multi-factorial)
- chronic myeloproliferative disorders
- mediastinal fibrosis
- sarcoidosis
- metabolic disorders
- cancer
Steps to diagnosing pulmonary HTN
- echocardiogram (estimate pulm. a. pressure & ID heart disease)
- CXR, PFTs (ID lung disease - restriction/obstruction…)
- Ventilation-Perfusion scan (ID thromboembolic disease)
- Other: sleep study, HIV test, autoantibody tests, liver f(x) test…
- Cardiac catheterization (determine severity)
Treatment of pulmonary HTN
1. treat underlying disease
- give O2 long-term if needed (increases survival!)
- thromboendarterectomy
- NEW drugs targeting endothelial pathway signaling
- anti-coagulation
Last ditch: lung transplant, vasodilators ONLY if no other Tx works
Drugs that target endothelial signaling pathways for pulmonary HTN
- Endothelin R antagonists
- Increase NO (ie: PDE-5 Inhibitors)
- promote prostacyclin pathway
reticular lung infiltrates on xray
= interlacing linear shadows (mesh-like)
- if also have fine nodules = “reticulonodular”
“honeycombing” of lungs on CXR
Coarse reticular shadows w/ cystic changes
* indicative of chronic inflammation*
“ground glass opacity” on CXR
= increased lung density (whitish) which does NOT obscure vessels
interstitial lung disease processes associated w/ Upper lung fields
silicosis or Coal workers’ lung
*most others affect the lower lobes more
interstitial lung disease processes associated w/ Pleural changes
- asbestosis
- Systemic lupus erythematous (SLE)
- Rheumatoid arthritis (RA)
interstitial lung disease processes associated w/ lymphadenopathy
sarcoidosis
organic dusts and interstitial lung disease
Causes: birds Ags, mold (farm environment, hot tubs, AC etc.)
when inhaled cause Sx:
- acute (dyspnea, fatigue; patchy infiltrates)
- chronic (interstitial inflammation, immune rxn; diffuse infiltrates)
characteristic appearance of CT for hypersensitivity pneumonitis
very diffuse: w/ micronodules and ground glass infiltrates
Radiation-induced Interstitial Lung disease
= damage to pneumocytes & vasc. endothelium, appear w/ straight edges on CXR!
- Pneumonitits: subacute (2-6 mo.), cough, fever, dyspnea; can treat w/ steroids
- Fibrosis: chronic (mo - yrs), dyspnea & decreased lung V; NO response to Tx
idiopathic pulmonary fibrosis
= most common type of Interstitial lung disease!
Sx: gradual dyspnea, old onset (50-70), crackles, clubbing
Dx: looks like Usual Interstitial Pneumonia (“UIP”) on CT… BUT has fibroblastic foci! (histo: temporally heterogenous)
Tx: only lung transplant
Hallmark of sarcoidosis
(systemic, but can cause a type of Interstitial Lung Disease)
=> NON-caseating granulomas
often asymptomatic
Loffgren’s syndrome
a type of sarcoidosis w/ 80% spontaneous remission;
characteristic Sx: dry cough, dyspnea, erythema nodosum, & arthralgias
Reactivation of (lung) infections
- mech
- common organisms
is a consequence of impaired T cell function
Common perpetrators:
TB, CMV, Ebstein-Barr virus, herpes-8 virus, toxoplasma, papilloma virus
aspergillus infection
= opportunist, cannot infect unless impaired neutrophils
–> causes invasive (acute) or chronic aspergillosis.
Risk factors: neutropenia, corticosteroids
Invasive aspergillosis
Acute infection, in patients have severe PMN dysfunction;
(hematopoetic stem cell transplant, solid organ transplant, or AIDS)
==> tracheobronchitis & other organ infection (spreads by blood)
neutrophil opportunists that commonly infect lungs
- aspergillus
- mucormycosis (also affects brain; risk w/ Diabetes, Fe overload)
- candidiasis
(mucosal if T cell def., deep tissue/skin if neutrophil def.)
HIV pathogenesis in lungs
- binds to lung cells w/ CD4 Rs
- lyses & depletes T helper cells
- -> impaired cell-mediated immunity, humoral immunity, and decreased macrophage activation.
Impact of HAART on HIV
Highly Active Anti-Retroviral Therapy
- lower viral loads
- higher CD4 levels (may even reach normal!)
- fewer opportunistic infections
- but: not a cure.
histological evidence of pneumocystis infection
foamy alveolar casts —> w/ pneumocystis organisms inside
** almost exclusively w/ HIV or AIDS **
pneumocystis jiroveci infection (in lungs)
fungal infection of lungs, causes type I pneumocyte damage;
= ubiquitous, only infectious if immunocompromised.
*does NOT grow in culture! (need bronchial biopsy to Dx)
Tx: bactrim (trimeth-sulf.) & corticosteroids.
prophylaxis if CD4 <200
norcardiosis
opportunistic infection after solid organ transplant,
–> pneumonia & systemic disease (skin and CNS)
bc lack ability to contain and kill the infection.
CMV lung infection
= reactivation of dormant virus,
usually: early after transplant if not on prophylaxis OR w/ HIV
* affects many organs/systems.
non-infectious complications from immunosuppression
or if immunocompromised
- more common bc of longer survival (w/ HAART)
- cancer (lymphoma & kaposi’s sarcoma)
- drug toxicity
- airflow obstruction
- pulm. HTN
primary histoplasmosis
Common in affected areas, often asymptomatic,
–> Most problems long after initial infection; found bc:
- nodule confused w/ cancer
- complications from location of nodule calcification
- disseminated disease if immunocompromised.
Exposure: Ohio river valley, up into MN & WI
Dx: Serum test = high diagnostic power
benign nodule presentation
calcification pattern: central, laminated, total calcification
* not involving hilar nodes
treatment of histoplasmosis
- oral itraconazole for 6 moonths
- if critically ill: IV for 1st 2 weeks, then #1
Blastomycosis
appears as (lobar) pneumonia that doesn’t respond to antibiotics, w/ coughing up pus, +/- crusty skin lesions.
* do NOT just pick 2nd antibiotic if “pneumonia” that doesn’t respond!
Exposure: similar to histoplasmosis (NW wisconsin/N minnesota + all areas covered by histo too)
* up to 3 month lag period btwn infection & Sx!
Dx: serum test not helpful
