- Airway/Airflow (V)

- Vascular/Blood flow (Q)

- Parenchyma (Dl)

- pH

- PO2 (PaO2)

- PCO2 (PaCO2) --> <35 mmHg caused by hyperventilation and >45 mmHg caused by hypoventilation

- Oxygen transport: Depends on pO2, Hb, and cardiac output (Q) --> SO2T= CaO2 x Q

- Oxygen content (CaO2): Dissolved O2+oxy-Hb = (pO2 x 0.0003) + (1.34 x Hb sat x Hb) --> 20.2 with 99% sat and Hb of 15 (Normal)

- Oxygen saturation: Dependent on pO2 and the shape of oxy-Hb --> Right shift for decreased pH and increased pCO2 and temp

- Hypoventilation --> Due to coma or drug overdose

- Ventilation/perfusion mismatch --> Most common cause

- Right to left shunt

- Diffusion abnormality

- Clinically most important cause of hypoxemia

- V/Q mismatch occurs naturally and in disease --> Naturally in the base of the lung

- Disease states most often result in perfused but under-ventilated areas of the lungs

- Normal: Thesbian veins and bronchial to pulmonary venous anastamosis

- Disease: Intracardiac and extracardiac

- Depends on the thickness of alveolar membrane, number of capillaries perfused, surface area available and concentration of Hb in blood

- Usually O2 only needs 0.25 s to fully load on Hb in the lungs

- RBCs usually take 0.7 s to traverse capillary bed

- During extreme exercise or disease states, capillary traversing time can be exceeded by necessary loading time

- DlCO: Clinical test for gas diffusion --> Decreases when surface area is decreased

- Inhalation of gastric acid and contents or other materials (chemical pneumonia or obstruction)

- Inhalation of mouth bacteria that may result in an overt bacterial pneumonia

- Abnormal entry of solid or liquid into the LRT

- Normal persons may regularly aspirate small amounts of material

- Consequences depends on the nature of the aspirate, amount, and the competence of clearing mechanisms in the lung

1. Aspiration of gastric acid (pH <3) may provoke acute respiratory failure and death

2. Foreign body aspiration --> Mechanical obstruction with or without infection

3. Aerobic/anaerobic pulmonary infections

- Alcoholism or drug overdose

- Epilepsy

- CNS lesions (stroke/dementia)

- Swallowing dysfunction or esophageal disease

- Oral inflammation

- Common denominator --> Alteration in level of consciousness or esophageal dysfunction

- Caused by multiple organisms --> Usually a mix of anaerobic and aerobic organisms

- Bacteroides fragilis --> Penicillin resistance and abcess formation

- Requires specific culture conditions

- Mixed flora on gram stain

- Putrid secretions

- Location of infiltrate --> Right>Left, posterior of UL and superior of LL (recumbent), and basal segments of LL (upright)

- Presence of oropharyngeal infection

- Must first exclude TB

- Aspiration pneumonia

- Lipoid pneumonia

- Necrotizing pneumonia

- Lung abcess

- Empyema

- Symptoms usually present for several weeks (fever, cough, fatigue, and chest pain)

- Exclusion of other possibilities -- Bronchial obstruction, TB/fungal infections, and cavitating cancer

- Characteristics: Thick-walled irregular cavity associated with pneumonia

- Air-fluid level usually present

- Size: 1-13 cm in diameter

- Multiple adjacent cavities present

- More extensive and lethal --> Infection begins to digest the lung more extensively

- Hemoptysis may be present

- Putrid sputum (60-70%)

- Pneumonia erodes through the pleura and infects the pleural cavity

- Purulent infection of the pleural space

- Exudate effusion

- Rapid loculation --> Can form multiple different empyemas --> Hard to drain with chest tube if this occurs

- Can be used for many things

- Confirm a diagnosis

- Follow disease therapy

- Evaluate symptoms

- Pre-postoperative evaluation

- Disability evaluation

- Research studies

- Flow rates

- Lung volumes

- Gas transfer (Diffusion capacity)

- Respiratory Muscle Strength

- Not easy to properly perform --> Patients need to be coached to get tests with best effort

- Recorded as % predicted values

- Normal is >80%, except FEV1/FVC is >70%

- Volume of air exhaled with maximal effort after a maximal inspiration

- Abnormal is <80%

- Volume of air exhaled in the 1st second of FVC

- Abnormal: <80% --> Reflects large airway obstruction

- FEV1/FVC ratio >70%

- Low FEV1/FVC ratio, low FEV1 and normal FVC

- Causes: COPD, asthma, and chronic bronchitis

- Assess bronchodilator response to differentiate between asthma and COPD/chronic bronchitis

- Normal FEV1/FVC ratio, low FEV1 and low FVC

- Diagnosis of restriction cannot be determined by spirometry alone --> Must go to lung volumes next

- Causes: Pulmonary fibrosis, kyphoscoliosis, neuromuscular disease, and obesity

- Forced expiratory flow rate between 25-75% of FVC

- Relatively effort independent part of the expiratory process

- Abnormal is <65% --> Reflects small airway obstruction

- Calculated by connecting the 25% and 75% points of the volume/time curve

- Expiratory loop on the top and inspiratory loop on the bottom

- Obstructive pattern: Severe scooping

- Restrictive pattern: Decreased FVC and FEV1

- Fixed obstruction pattern: Flattening of both expiratory and inspiratory limbs --> Tracheal stenosis or goiter

- Variable Intrathoraic Upper Airway Obstruction pattern: Expiratory limb truncated --> Tracheomalacia or tracheal mass below the vocal cords

- Variable Extrathoracic Upper Airway Obstruction pattern: Inspiratory limb truncated --> Tracheomalacia or vocal cord abnormalities

- Total Lung Capacity: Maximal amount of gas our lungs can hold after total inhalation (Encompasses all lung volumes)

- Functional Residual Capacity: Volume of gas in our lungs at the end of normal exhalation --> TLC - IC = FRC

- Vital Capacity: Maximum amount of gas we can expire --> IC+ERV

- Forced Vital Capacity: Maximum amount of gas expired after a forced maneuver

- Residual Volume: Amount of gas remianing in our lungs after a forceful exhalation

- Tidal Volume: Amount of air that is moved during tidal breathing

- Inspiratory Capacity: Amount of air inhaled from FRC to TLC

- Expiratory Reserve Volume: Additional volume of air that can be exhaled beyond normal expiration (VT) 

- Helium dilution technique: Pt connected to spirometer containing a known volume and concentratin of helium --> Helium concentration is determined again after pt breathes 

- Body plethysmography technique (Body box): Patient inhales against a closed shutter --> Volume nad pressure in the box increases --> Lung volume calculated (P1V1=P2V2)

1. Increased lung volumes --> Emphysema and reversible airway obstruction (asthma)

- Normal FVC, low FEV1, low FEV1/FVC, high FRC, normal/high TLC and high RV

2. Decreased lung volumes --> Pulmonary edema, fibrosis, and neoplasms, and chest wall deformities and neuromuscular diseases

- Low FVC, low FEV1, normal FEV1/FVC, low FRC, low TLC, and low RV

- Measures the conductance of the lungs for CO which is a surrogate for gas-exchange of O2 and CO2

- Reduced DLCO --> Anemia, emphysema, pulmonary resection, interstitial lung disease, pulmonary vascular disease

- Increased DLCO --> Polycythemia, pulmonary hemorrhage, left-right shunt, CHF, and asthma

- Helps differentiate between restrictive lung disease with and without parenchymal involvement

- Values often decrease before spirometry --> Especially in ILD

- Tests the overall capacity of the respiratory system to endure maximal ability

- Have patient breath as deep and fast as they can for 12 seconds

- Results --> Expressed in L/min --> Low in neuromuscular weakness

- Tested with pressure manometers

- Maximal Inspiratory Pressure (MIP): Mainly the diaphragm function

- Maximal Expiratory Pressure (MEP): Mainly the abdominal muscle function

- Decreased in neuromuscular weakness

1. Flow-volume loop

2. FEV1/FVC --> Determines obstruction

3. FEV1, FVC, and FEF25-75

4. Look at lung volumes

5. Look for mixed pattern on spirometry

6. Look at DLCO values

- Right lung: 3 lobes (upper, middle, and lower)

- Left lung: 2 lobes (upper with lingula and lower)

- Lobes divided into segments --> 10 lobules per lobe

- Trachea --> Bronchi --> Bronchioles --> Terminal bronchioles --> Respiratory bronchioles --> Alveolar ducts --> Alveoli

- Acinus --> Fundamental unit of the lung (3-5 acini form a lobule)

- Bronchial mucosa: Pseudostratified ciliated columnar epithelium, Goblet cells, and submucosal mucus glands

- Alveolar wall: Capillary/epithelium basement membranes, sparse collagen, elastic fibers, rare mast cells, and lymphocytes

- Alveolar lining cells: Type I and Type II pneumocytes

- Kohn's pores between alveoli --> Allows for communication

- Abnormal enlargement of airspaces distal to the terminal bronchiole due to destruction of acinar walls without obvious fibrosis

- Classified according to location --> Centriacinar, panacinar, paraseptal, and irregular

1. Centriacinar: Affects proximal acinus (respiratory bronchiole) --> 95% of cases and most severe in upper lobes

- Associated with smoking

- Lungs not voluminous

2. Panacinar: Acini uniformly enlarged distal to respiratory bronchiole --> More common in lower lobes

- Associated with alpha-1 antitrypsin

- Voluminous lungs

3. Paraseptal: Involves pleura and lobular septa --> Upper lungs

- Adjacent to scarring/fibrosis --> Results in pleural blebs

4. Irregular: Acinus is irregularly involved --> Associated with localized scarring

- Based on protease-antiprotease and oxidant-antioxidant imbalance

- Smoking overpowers antioxidants and generates a surplus of reactive oxygen species

- Alveolar wall destruction occurs due to elastase release from neutrophils

- Due to chronic irritation of airways by inhaled substances

- Strongly associated with smoking

- Pathology: Chronic inflammation of bronchi/bronchioles with hypertrophy of bronchial submucosal glands, Goblet cell metaplasia, mucus plugging, and fibrosis

- Small airways may become obstructed

- Bacterial/viral infections may trigger acute exacerbation

- Permanent dilation of bronchi and bronchioles due to destruction of the bronchial wall by necrotizing infections/pneumonia

- Causes: Congenital (CF) and bronchial obstruction

- Pathology: Usually lower lobes bilaterally, airway dilated 4x normal, intense actue and chronic inflammation, mucosal ulceration, squamous metaplasia, and fibrosis

- Chronic disorder of airways associated with bronchoconstriction and decreased air flow --> At leas partially reversible

- Symptoms: Wheezing, breathlessness, chest tightness, and cough

- Inflammation results in increased responsiveness to stimuli --> Bronchospasm

- Involved cells: Eosinophils, mast cells, macrophages, T-cells, neutrophils, and epithelial cells

- Pathology: Distended lungs, occlusion of bronchi with mucus plugs, thickened BM, edema, increased submucosal mucus glands, and hypertrophy of smooth muscle

- Infection of the lung parenchyma by a variety of organisms

1. Bacterial pneumonia --> Lobar or bronchopneumonia --> Entire air spaces become filled with inflammatory cells but alveolar membrane still intact

- Stages of inflammation: Congestion, red hepatiization, grey hepatization, and resolution

- Pleuritis: Inflammation of the pleura

2. Viral pneumonia --> Inflammatory infiltration of the interstitium

3. Aspiration --> Giant cells and granulomas seen in interstitium

4. Pneumonia abcess --> Alveolar membrane is degraded by infectious process

- Obstruction seen by low FEV1/FVC ratio

- Spirometry varies over time --> Improves after bronchodilator

- Exacerbations can also be determined by a peak flow meter diary

- Histamine or methacholine challenge testing shows the amount of hyperresponsiveness of the airway

- FEV1 values show an early and late phase response

- Goblet-cell hyperplasia

- Sub-basement membrane thickening

- Submucosal collagen deposition

- Submucosal gland hyperplasia

- Edema and cellular infiltration (eosinophils) --> Cytokine release leading to late phase reaction

- Bronchial and bronchiolar mucosal inflammation and edema

- Airway smooth muscle constriction

- Excess mucous secretion and build up in the lumen

- Chronicity of inflammation leads to airway remodeling --> irreversible fibrosis and narrowing

- Increased incidence of asthma in patients with higher IgE levels (allergies)

- No major single-gene cause --> Complex gene relationship

- ORMDL3 gene --> Very common but has very little allele risk effect on asthma incidence

- Genetic and environmental factors

- 3-5x relative risk for asthma with a sibling with asthma

- Patients with asthma have a higher likelihood of having a Th2 cell response --> Usually due to the hygiene hypothesis

- Th1 cells --> IFN-g and IL-2 release --> Cellular immune response

- Th2 cells --> IL-4 and IL-5 release --> Antibody response and allergic inflammation

- Symptoms: Wheezing, breathlessness, chest tightness, cough, and sputum production

- Associated conditions: Rhinitis, sinusitis, nasal polyposis, and atopic dermatitis

- Pattern of symptoms: Seasonal, continuous, episodic, and nocturnal

- Recurrent exacerbations due to allergens, irritants, exercise, viral infections, and cold air

- Exam may be normal in between episodes

- Lung exam: Wheezing and prolonged expiratory phase

- Chest exam: Hyperinflation and accessory muscle use

- Upper airway exam: Rhinitis, sinusitis, and nasal polyps

- Skin exam: Eczema

- Markers of atopy: Increased serum IgE and eosinophil count

- Positive allergy skin testing --> Helps document specific allergies that may aggravate asthma

- Chest X-ray: Normal in most cases but can show hyperinflation or mucous plugs

- May lead to actue respiratory failure and death due to hypoventilation, hyperinflation, and respiratory muscle fatigue

- Risk factors: Previous near-fatal episodes

- Patient must have an action plan if symptoms worsen at home

- Repetitive administration of rapid-acting inhaled B2-agonist (albuterol)

- Early introduction of systemic glucocorticosteroids

- Oxygen supplementation

- Patient must be closely monitored

- Endotracheal intubation and mechanical ventilation may be necessary

- Disease resulting from the interaction between a susceptible host and potneitally modiable environmental factors

- Characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung

- Inflammatory response is due to noxious particles or gases

- Includes the disease processes of emphysema, chronic bronchitis, and asthma or a mixed/complex form

- Progression of shortness of breath

- Cough

- Possible sputum production

- Wheeze

- Over 5% of the population --> 3rd leading cause of death

- Total economic costs --> $49.9 billion in 2010

- Mortality for COPD is increasing for all groups but especially for females

- Environmental exposures (smoke, dust, chemicals, and air pollution)

- Genetic: Only 20-25% of smokers, alpha-1 antitrypsin deficiency, and chromosome 4 and 15 mutations

- Lung development

- Gender --> Females!!

- Age

- Respiratory infections

- Socioeconomic status

- Asthma/bronchial hyperactivity

- Chronic bronchitis

- Accounts for 1% of all COPD

- AAT is a glycoprotein coded by chromosome 14 that acts on elastase

- Without AAT, elastase breaks down elastin and causes protease-antiprotease imbalance --> Lung damage

- Large cause of emphysema

- Results in alveoli and terminal bronchiole collapse during expiration

- Small airway disease --> Airway inflammation, fibrosis, luminal plugs, and increased resistance

- Parenchymal destruction --> Loss of alveolar tethering and attachments and decreased elastic recoil

- Ultimately leads to increased compliance of the lung and hyperinflation (air trapping)

- Greatly increased reserve volume in the lung --> Air trapping

- Forced residual capacity is greatly reduced 

- Inspiratory capacity is greatly reduced

- Tidal volume may still be the same but it's occuring at a much higher total lung volume

- Total lung capacity is increased as well due to hyperinflation

- Hyperinflation progressively increases as disease progresses

- Should be considered in any patients with dyspnea, chronic cough or sputum production and in patients with history of exposure to risk factors

- Spirometry is required to diagnose --> Post-bronchodilator FEV1/FVC <0.70

- Classification: FEV1 >80% (I), FEV1 50-80% (II), FEV1 30-50% (III) and FEV1 <30% (IV) --> Based on post-bronchodilator testing

- Relieve symptoms --> SOB, cough, wheeze

- Improve exercise tolerance --> Reduced exercise tolerance leads to inactivity which leads to deconditioning and more SOB

- Improve health status

- Prevent disease progression

- Prevent and treat exacerbations

- Reduce mortality

1. Smoking cessation!!!!!!! --> Best way to reduce mortality and risk of exacerbation

2. Influenze vaccine annually

3. Pneumococcal vaccine

4. Control of environment irritants

5. Medications: Beta 2-agonists, anticholinergics, and corticosteroids

- Short acting are better suited for inpatient setting and long acting are better for outpatient --> Easier compliance and reduce exacerbations

- Inhaled corticosteroid therapy helps improve symptoms, lung function and quality of life

6. Oxygen therapy --> Prolonged survival and improves lung function

- Prescribed for patients with pO2 of <88% on RA or in patients with symptoms of cor pulmonale

- Multidisciplinary program

- Goals are to improve:

1. Exercise capacity

2. Independence

3. Symptoms

4. Health status

5. Quality of life

- Lung function not affected

- Resource utilization is often decreased

- Acute event characterized by a worsening of the patient's respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication

- Consequences: Negative impact on quality of life, impact on symptoms, increased economic costs, increased mortality, and accelerated lung function decline

- Arterial blood gas: Evaluates for hypoxemia or hypercarbia

- Chest X-ray: Useful to exclude alternative diagnoses

- ECG: may aid in diagnosis of coexisting cardiac problems

- CBC: Identify anemia, bleeding, or polycythemia

- Purulent sputum: Indication for antibiotic therapy

- Biochemical tests: Detects electrolyte disturbances, diabetes, and poor nutrition

- Spirometric tests: NOT reccommended!!

- Management: Minimize the impact of the current exacerbation and to prevent future exacerbations

- Treatment: Oxygen, bronchodilators, systemic corticosteroids (inpatient only), antibiotics to clear any infection that may have precipitated event

- Increased intensity of symptoms

- Severe underlying COPD

- Abnormal vitals

- Failure of an exacerbation to respond to initial treatment

- Presence of serious comorbidities

- Frequent exacerbations

- Older age

- Insufficient home support

1. Adrenergic: No adrenergic fibers to airways --> A and B receptors on bronchial smooth muscle surrounding airways

- A receptors: Bronchoconstriction

- B receptors: Bronchodilation (muscle relaxation)

2. Cholinergic: Present in the large bronchi to the 5th division

- Afferent fibers --> Irritant receptors

- Efferent fibers --> M receptors that bind ACh --> Bronchoconstriction and mucous secretion

- Primarily due to mast cell release of histamine and leukotrienes

- Located on mucosa and within submucosa

- Degranulated triggered by IgE/antigen binding

- Effects of mediators: Bronchoconstriction, mucous production, mucosal edema, and inflammation

- Leukotriene production mediated by phospholipase and 5-lipoxygenase

1. Metered Dose Inhalers: Disperes a fixed amount of drug, requires education on how to use it though, and requires an aerosolized carried vehicle

2. Aerosols: Solution of medication, converted into a mist, requires less coordination but must be delivered over a longer period of time

3. Spacers: Used in conjunction with an MDI, improves drug delivery, and mandatory with corticosteroid inhalers

- Albuterol (short acting) and salmeterol (long acting)

- First line agents --> Bronchodilators

- Binds B-2 receptors --> Smooth muscle relaxationdue to increased cAMP

- Administration: Inhalation, oral and parenteral

- Length of side chain determines the duration of action

- Effects: relaxes smooth muscle, improves diaphragmatic contraction, suppresses mast cell degranulation, enhances mucociliary function, decreases microvascular permeability, and inhibits phospholipase A

- Systemic effects depend on the dose

- Side effects: Muscle tremor, tachycardia, K, Mg, Ca, and PO4 decrease, increased glucose, anxiety, and restlessness --> All depends on route of administration

- Indications: Acute exacerbations and chronic therapy for maintenance and prophylaxis

- Theophylline --> Medium bronchodilator --> 2nd or 3rd line

- Mechanism: Non-specific PDE inhibition

- Effects: Bronchodilation, increased diaphragmatic contraction, accelerated mucociliary clearance, decreases mast cell degranulation, and mild diuretic

- Requires maintenance and loading dose IV and variable oral absorption

- Metabolism: P450 --> Variable t1/2 (2-12 hours) and clearance by many factors

- Requires monitoring!! --> Variable side effects

1. Side effects: Nervousness, N/V, anorexia, abdominal pain, headache and sleeplessness initially

- Severe --> Seizures and cardiac arrhythmias at higher levels

- 4% of adults cannot tolerate at all and ~20% cannot tolerate therapeutic levels

2. Uses: Acute exacerbations and maintenance therapy only in refractory disease

- Similar to atropine but quaternary ammonium compounds --> Not systemically absorbed

- Ipratropium bromide and tiotropium bromide

- Mechanism: ACh M receptor antagonists --> Bronchodilation and decreased mucous secretion

- Effects: Medium bronchodilators, reduced hospitalization, additive effects with other drugs

- Disadvantage: Slow onset of action (30-60 min)

- Side effects: Dry mouth and cough --> No change in sputum or mucociliary clearance

- Uses: Acute exacerbations (ipratropium only) and both for maintenance therapy

- Tiotropium has a longer duration of action --> Once daily

- Slow onset of action (6-12 hours)

- Fluticasone --> Inhalation

- Mechanism: Inhibits phospholipase A, reduces B receptors, and decreases inflammation

- Administration: Oral, IV and inhalation

- Side effects: Dysphonia, oral cadidiasis, adrenal suppression, cough, cataracts, glaucoma, and osteoporosis

- More systemic side effects with intravenous administration

- Uses: Acute exacerbations, maintenance therapy, and prophylaxis to prevent future exacerbations

- Nedocromil --> Not available in the US --> Tastes terrible!!

- Mechanism: Prevents mediator release

- Administration: Inhalation only

- Uses: First line for prevention but NO use in acute

- Side effects: Throat irritation, unpleasant taste, cough, bronchospasm, transient rash, myositis, dermatitis, and rebound airway hyperreactivity

- Montelukast --> LTD4 receptor antagonist

- Slow onset of action (days/weeks)

- Inhibit the effect of leukotrienes on the airways

- Not bronchodilators --> Disease modifying agents

- Omalizumab/Xolair --> Recombinant DNA-derived IgG1 kappa antibody

- Mechanism: Selectively binds human IgE --> 96% decrease within one hour

- Peak serum concentration in 7-8 days

- Administered SC every 2-4 weeks

- Elimination: Hepatic reticuloendothelial system

- Decreases asthma exacerbations

- Limits mast cell and basophil mediator release

- Must be older than 12 years

- Side effects: Malignant neoplasms, anaphylaxis, injection site reactions, viral infections, sinusitis, headache, and pharyngitis

- Uses: Moderate to severe persistent asthma, symptoms inadequately controlled by steroids, and patients with positive skin testing

- Tiny gram negative coccobaccilli --> High maintenance growth --> Cannot culture!!

- Transmission: Aerosolized droplets

- Colonization: Transient nasopharyngeal carriage

- Incidence: Most common and most severe in children <1 year --> Also in 11-12 year olds

- Entry, multiplication and spread: Attachment to ciliated epithelium --> Causes local ciliostasis and tissue damage

- Systemic toxicity due to toxin spread

- Disease caused by B. pertussis

- Incubation period: 1-3 weeks

- Catarrhal Phase: Looks alot like other respiratory diseases --> Non-specific cough, SOB, fever

- Dry cough develops in the last few days of catarrhal phase

- Paroxysmal phase: Distinctive cough

- Convalescent Phase: Diminished symptoms but cough persists for months

1. Filamentous hemagglutinin: Surface protein that mediates the attachement to ciliated epithelial cells

2. Pertussis toxin: A/B toxin that catalyzes the transfer of ADP-ribose from NAD to G proteins --> Disrupts cell signaling leading to cell death

- Results in increased respiratory secretion and mucus

3. Endotoxin

4. Tracheal cytotoxin

5. Heat labile toxin: Causes smooth muscle contraction

6. Adenylate cyclase: Catalyzes endogenous production of cAMP

1. Diagnosis: Primarily made based on clinical presentation

- Culture is only effective for the first 2 weeks

- Serology is only effective for 2-8 weeks

- PCR is only effective for the first 4 weeks

2. Management: Azythormycin, erythromycin, clarithromycin, and supportive therapy

- Supportive therapy: Monitoring of vitals, nasotracheal suctioning, O2 supplementation, and parenteral nutrition and hydration

3. Prevention: Vaccination with the acellular vaccine

- Initial doses given at 2,4,6, and 18 months

- Boosters of Tdap for 11-12 year olds and 19-64 year olds

- Tiny Gram negative coccobacilli --> Highly pleomorphic on staining

- Fastidious nature requiring specific culture --> Can culture though

- Encapsulated and non-encapsulated strains are possible --> 6 strains are present (Type B most invasive)

- Invasive diseases: Bacteremia, meningitis, epiglottitis, septic arthritis, cellulitis, and pneumonia

- Non-invasive: Otitis media, sinusitis, and conjunctivitis

- Tranmission: Aerosolized droplets --> Almost no cases after vaccine implemented

- Risk factors: Immune status, genes, underlying pulmonary disease, antecedent viral infection, day care, siblings, and cigarette smoking

- Increased risk in COPD patients and smokers --> 3-10% of cases

- Attachment to non-ciliated epithelial cells and mucus --> Causes ciliastasis and sloughing from adjacent epithelial cells

- Breaks down tight junctions allowing bacteria to invade within cells

- Cells pass into submucosa and disseminate

- Capsule --> Contains ribose sugars which we have less antibodies to

- Endotoxin

- IgA1 protease

- Pili and other surface adhesins

- Diagnosis: Culture is possible but still hard so direct detection best

- Treatment: Lots of resistance so use ceftriaxone for invasive and macrolides or quinolones for non-invasive

- Prevention: Vaccination with conjugate vaccine containing PRP (ribose) capsule

- Clinical: symptoms are usually insidious and progressive with a non-productive cough, "velcro" rales, clubbing of digits and rarely fever

- Radiology: Peripheral abnormalities in lung bases on HRCT, bilateral subpleural cysts (honeycombing) and traction bronchiectasis possible

- Pathology: Patchy lung involvement with temporal heterogeneity, fibroblastic foci, dense fibrosis, lung remodeling, and interstitial inflammation

- Minor features: Type II pneumocyte hyperplasia, macrophage accumulation, bronchiolar metaplasia, subpleural blebs, smooth muscle proliferation, and squamous metaplasia

- Diffuse interstitial disease characterized by several months of dyspnea

- Tends to occur in younger patients than UIP --> Cough, SOB, and fatigue

- CXR: LL zones, bilaterally and symmetric, patchy alveolar opacifications, and reticular changes

- HRCT: Ground glass opacities

- Findings most closely relate to HP and COP

- Treatment: Steroids

- Causes: Often caused by autoimmune diseases such as SLE, RA, and SCL

- Diffuse inflammatory process of uncertain etiology

- Involves the alveolar walls, bronchovascular sheaths, and the pleura

- Homogenous throughout sections

- Fibrosis is mild if present at all

- Must consider HP, collagen vascular diseases, resolving infection, and LIP 

- Organizing pneumonia: Pattern of lung injury and repair with airspace organiziation --> Seen in a wide variety of diseases

- Causes: Organizing infections, organizing DAD, drug and toxic reactions, CVD, HP, chronic eosinophilic pneumonia, and airway obstruction

- When no etiology can be identified as bronchiolitis obliterans organizing pneumonia (BOOP)

- Clinical: Prior upper respiratory tract, 50-60 years old, non-smokers, cough, dyspnea, fever, night sweats, myalgias, and increased ESR

- Radiology: LL patchy airway space consolidiation, air bronchograms, ground glass opacity, and nodules

- Pathology: Dense airspace aggregates of loose connective tissue in ground substance with lymphocytes, plasma cells, and histiocytes, fibrin seen focally, and lung architecture preserved

- Fibrosis should NOT be a prominent feature

- Treatment: Steroids!!

- Lesion of the small airways linked to smoking

- RB if left untreated can lead to desquamative interstitial pneumonia (DIP) --> DIP presents later

- Presentation: Associated with smoking, more males than females, cough and SOB

- Pathology: Scant inflammation surrounding terminal airways, bronchiolar metaplasia, variable number of lightly pigmented macrophages in airspaces, and scant peribronchial fibrosis

- Excellent prognosis

- Diffuse lung disease typically occuring in smokers a decade younger than UIP

- Extensive occupation of airspace  by desquamated cells (macrophages)

- Associated with RB, mild interstitial fibrosis and mild chronic inflammation

- Symptoms: Insidious onset of cough, dyspnea, and digital clubbing --> More severe than RB

- Prognosis is very good if patients quit smoking

- Results from the inhalation of environmental antigens

- Characterized by small poorly formed granulomas near the respiratory or terminal bronchioles

- May resemble UIP but will resolve if exposure is removed

- Farmers Lung: Exposure to actinomycetes spores

- Bird Fancier's Disease: Exposure to protein from bird feathers, serum and excrement

- Air conditioner lung: Exposure to the thermophilic bacteria in heated water reservoirs

- Acute symptoms: Malaise, dyspnea, dry cough, fever, and chills within 4-6 hours of exposure

- Subacute: Gradual development of cough, dyspnea, fatigue, and mild hypoxia

- Chronic symptoms: More subtle symptoms and more progressive

- Immunologicall mediated --> Increased MIP-1a and IL-8 levels, increased CD4 and CD8 cells, circulating immune complexes, and small non-caseating granulomas form

- Pathology: Patchy nodular pattern --> Chronic interstitial inflammation associated with bronchiolitis and small non-caseating granulomas including multinucleated giant cells

- Diagnosis: History of exposure, serologic testing, radiologic findings, and biopsy if necessary

- Treatment: Remove exposure and prednisone therapy to recover faster

- SLE, RA, and SCL

- Different patterns may be seen --> NSIP, UIP, bronchiolitis, and pleuritis

- Lung reaction to carbon pigment --> Engulfed by macrophages

- Range of syndromes: Asymptomatic anthracosis, simple CWP, and complicated CWP

- Simple CWP: Localized macules and nodules of pigment-laden macrophages and fibrosis

- Complicated CWP: Large blackened scars of dense collagen and pigment deposition --> Takes a long time to develop

- Asbestosis

- Silicosis

- Paraquot

- Chemotherapeutic agents

- Other drug reactions such as amiodarone

- Dyspnea on exertion

- Other disease specific symptoms

- Late inspiratory crackles on exam

- Restrictive pattern with reduced TLC and DLCO on PFT

- Abnormal CXR or CT scan

- Pathology: Due to abnormal wound repair --> Fibrosis

- Best seen using HRCT

- Increase in peripheral linear markings

- Septal thickening

- Honeycombing --> UIP only

- Ground glass appearance (NSIP)

- Lung resection

- Obesity

- Diaphragmatic paralysis

- Neuromuscular disorders

- Pleural effusion, pneumothorax or blebs

- >20% decrease in TLC

- Airflow normal or increased

- DLCO usually decreased in parenchymal diseases --> First thing to decrease

- History and physical

- Consistent CT scan

- PFT findings --> TLC and DLCO

- Exclude other diseases

- Biopsy --> Confirm diagnosis, atypical features, and diagnostic precesion

1. UIP

- Fibroblastic foci

- Heterogeneous appearance

- Generally steroid resistant

- Honeycombing on HRCT

2. NSIP

- Inflammatory infiltration

- Homogeneous appearance

- Steroid sensitive

- Minimal fibrosis, fibroblastic foci, and honeycombing

- Must use pathology to make diagnosis

- Shorter history --> More rapid onset

- Systemic symptoms

- Steroid sensitive and reversible fibrosis

- Old Gold standard: Prednisone, azathiaprine and N-acetylcysteine --> Believed to reduce free radicals

- Interferon-g --> Help reduce inflammation

- Endothelin-1 receptor antagonist --> Good for PAH

- Pirfenidone --> Anti-fibrotic --> No real benefit shown

- Anti-TGF-b --> Great anti-fibrotic compound but may also promote GI cancers

- No approved drugs for UIP since it is not an inflammatory process

- No good anti-fibrotic medications available

- Oxygen supplementation and lung transplants are the best options

- S.H.I.T.F.A.C.E.D.M.D.

- Sarcoidosis

- Hermorrhage --> Idiopathic, Wegener's, Goodpasture, and Lupus

- Idiopathic Interstitial Pneumonia (UIP, DIP, COP/BOOP, LIP, AIP, RB-ILD)

- Tuberous sclerosis, Phakomatoses, LAM

- Failure (Heart)

- Asbestos/Amyloid

- Collagen Vascular Diseases

- Eosinophilic Lung diseases, Eosinophilic granuloma

- Drugs

- Malignancy

- Dirt, inhaled, organic or inorganic particles

- Systemic granulomatous disease of unknown etiology

- Involves the lungs in 90-95% of patients

- 60-80% will remit spontaneously

- Other organ involvement --> Skin, eyes, calcium metabolism, liver, CNS, heart, bones and joints

- Treatment: Steroids and possibly other anti-fibrotic agents --> Treat only if multiple organ involvement seen

- Epidemiology: More common than expected

- Diagnosis: Transbronchial biopsy --> Observation of the non-caseating granulomas

- Often a diagnosis of exclusion

- Layers of epithelioid cells and giant cells surrounding an inhaled agent or other antigen

- Is sarcoidosis autoimmune, hypersensitive or infectious?-- Possibly caused by beryllium exposure --> Beryllium has a known relationship with sarcoidosis --> With a certain HLA allele

- Stage I: Bilateral hilar lymphadenopathy only

- Stage II: Bilateral hilar lymphadenopathy with reticular pattern

- Stage III: Lymphadenopathy generally regresses and reticular pattern becomes more extensive

- Stage IV: Fibrosis seen

- Fever/fatigue, weight loss and malaise (30%)

- Asymptomatic (25%)

- Pulmonary symptoms (30-50%)

- Pulmonary involvement (>90%): Stage 0 (10%), Stage 1 (50%), stage 2 (25%), and stage 3/4 (15%)

- Lofgrens Syndrome: Erythema nordosum seen on the skin --> >95% specificity

- Infections: Mycobacteria, fungus, bartonella, whipples, schistosomiasis, and syphilis

- Malignancy: Lymphoma and other neoplasms

- Immunologic: Wegner's, Crohn's, HP, Beryllium exposure, and foreign body

- Steroids --> Most common and first line treatment

- Methotrexate

- Plaquenil --> Especially good for skin involvement

- Infliximab/adalinumab --> Anti-TGF-b antibodies

1. Acute: Fleeting, nodular, interstitial pattern in LL and ML zones may be normal on CXR

2. Subacute: Nodular, interstitial pattern in ML and UL may be normal on CXR. Diffuse micronodules, air trapping, and mild fibrotic changes on CT

3. Chronic: Interstitial pattern in ML and UL and may show fibrosis on CXR. Micronodules and fibrotic changes on CT. Looks like IPF

- Inhalation of crystalline silicon dioxide --> Most prevalent occupation disease

- Common exposure in sandblasting, Foundry work, stone cutters, glass makers, quarry workers, and construction workers

- Pathogenesis: Silicotic nodules in UL which over time coalesce to form large scars --> May progress to massive fibrosis with nodules in hilar lymph nodes

- Insidious in onset (10-30 years) --> May become apparent years after cessation of employment

- Radiographic pattern: UL predominant nodules, minority have coalescent nodules resulting in progressive massive fibrosis --> Eggshell calcifications

- May also have an acute presentation

- Associated diseases: Lung cancer, mycobacterial infection, scleroderma, RA, COPD, and chronic bronchitis

1. Diagnosis: History of exposure, consistent CXR findings, absence of another explanation, and exclude TB

- Biopsy usually NOT needed

2. Treatment: No specific treatment, symptomatic relief therapy (O2, rehab), rule out TB, and perhaps steroids

- Biggest thing is prevention --> Exposure is easily prevented through proper mask usage

- Often progressive and untreatable

- Pneumoconiosis caused by inhalation of asbestos fibers

- Characterized by slowly progressive pulmonary fibrosis

- Related diseases: Pleural effusion, focal and diffuse pleural plaques, lung cancer, and malignant mesothelioma

- Exposure sources: Construction and insulation, mining and milling, industrial applications (textiles/cement), non-occupational through clothing contact

- Associated diseases: small cell and non-small cell lung cancer and mesothelioma

- Symptoms present 20-30 years after exposure

- Progressive symptoms due to lack of further exposure

- PFT: Restrictive with low DLCO --> No obstruction

- CXR: Basilar interstitial disease, "shaggy heart border", or may be normal

- Plaques and effusions --> Early "badges" of asbestos exposure

1. Diagnosis: Reliable exposure history, definitive evidence of pulmonary fibrosis, and absence of other causes

2. Treatment: Smoking cessation, prevention of further exposure, supplemental O2 when needed, treatment of concurrent respiratory infections, and flu and pneumococcal vaccinations

- Prognosis: Depends on the extent of progression --> Usually slow progression though

- Inflammatory process involving the lung tissue beyond the bronchi --> Impairs gas exchange

- Either primarily alveolar involvement or primarily interstitial involvement

- Alveolar --> Consolidation and air bronchograms

- Interstitial --> Reticular pattern

- Possibly due to infectious or non-infectious causes

- Non-infectious: Vasculitides, acute chest syndrome of sickle cell disease, and lymphoma

1. Neutropenia --> Reduced numbers of neutrophils

2. Impaired chemotaxis

3. Impaired phagocytosis

1. T-cell impairment: Impaired coordination of cellular responses to pathogens, reduced CD4 cells and activated CD8 cells

- Susceptible to intracellular bacteria and viruses

2. Spelenctomy and B-cell impairment: Susceptibility to encapsulated organisms and impaired adaptive immunity

- Weak antibody response

- Breach of physical barrier --> Catheter or central line placement

- Compromise of functional barrier

- CD8 cells become more and more activated as disease progresses

- CD4 cell numbers steadily decline

- CD4 > 200: Bacteria and TB

- CD4 100-200: PCP, cryptococcus, bacteria and TB --> Polymicrobial infections

- CD4 <100: CMV, atypical mycobacteria and all above pathogens

1. Direct effect: Immunity is impaired directly by the cancer --> Hematologic malignancies or space occupying lesions

2. Indirect effect: Chemotherapy induced --> Bone-marrow suppression and transient neutropenia

1. Direct effect: Mechanical effect due to esophageal dysfunction and unchecked inflammation --> Progressive destruction and altered lung anatomy

- Bronchiectasis and pulmonary fibrosis

2. Immunosuppressant-induced --> Medication induced

- Prednisone --> Bacteria and pneumocystis

- Anti-TNF --> TB

- Methotrexate, cyclophosphamide, and sulfasalazine --> Bacteria, fungi, and viruses

- Both solid organ and bone marrow transplant

- Immunocompromise --> Induced suppression of the immune system to prevent graft rejection and impairment due to radioablation

- Pre-transplant serology of the recipient and donor can estimate the risk for certain pathogens

- Not generally related to immunosuppressive medications

- 0-1 month: Susceptible to donor-derived bacteria, recipient recurrent infection, and post-op infection

- 1-6 months: Opportunistic infections (PCP, CMV, fungal, TB, and protozoal)

- >6 months: Bacterial, CMV, influenze and RSV infections

- 50% of lung transplants develop CMV pneumonitis!!

- Highly immunocompromised beforehand due to radioablation

- 0-1 month: Bacterial, fungal, PCP, and toxoplasmosis --> Takes at least a month for transplant to engraft and begin to replicate in new host

- >1 month: Viral infections (CMV, parainfluenza, RSV, and HSV) and TB

- Diabetes, alcohol abuse, cirrhosis and uremia

- Immunocompromised due to impaired neutrophil chemotaxis

- Patients have a higher incidence of delirium and aspiration risk

- Frequent hospitalizations due to poor control expose patients to nosocomial infections

1. Bacterial

- Community-acquired

- Nosocomial: MRSA, Pseudomonas, ESBL

- Uncommon bacteria: Rhodococcus and Nocardia

2. Fungal

- Pneumocystis jiroveci

- Aspergillus

- Cryptococcus

- Histoplasma and Coccidiodomycoses

3. Viral

- CMV

- Influenza, RSV, and adenovirus

- At risk patients: Neutropenic, HIV-infected, and immunocompromised patients

- Symptoms: Malaise, mild dyspnea, low-grade fever, and anorexia --> May be very mild due to extremely mild immune response

- Exam: Minimal findings or crackles may be noted

- Imaging: Infiltrate on CXR and CT of thorax

- Microbiology: Sputum analysis and bronchoscopic lavage

- Treatment: Empiric antibiotics --> Must take into consideration extent of immunocompromisation

- At risk patients: HIV-infected with CD4 <200 and chronic steroid therapy

- Symptoms: Malaise, sweats, worsening dyspnea, and anorexia --> May be subacute!

- Exam: Minimal findings or crackles may be noted

- Imaging: CXR with interstitial/reticular infiltrate, pneumothorax and diffuse ground glass on HRCT

- Microbiology: Induced sputum for DFA and bronchoscopy may be required --> Methamine silver stain to identify PCP

- At risk patients: Neutropenic patients and patients on steroids

- Symptoms: Fever, malaise, hemoptysis (if vessels involved), rapidly worsening dyspnea and hypoxemia

- Exam: Mild-moderate hypoxemia and clear or minimal crackles

- Imaging: Pleural or apical disease seen on CXR, pleural involvement and alveolar disease on HRCT, and potential evidence of vascular invasion

- Microbiology: Sputum may show Aspergillus and bronchoscopy may be required

- At risk patients: Lung transplant, other solid organ transplants, bone marrow transplant, and HIV-infected patients

- Symptoms: 1-4 months after transplant and variable symptoms depending on immune status and degree of engraftment after BMT

- Exam: Clear or focal lobar findings

- Imaging: CXR may show nothing or interstitial/lobar infiltrate and HRCT may show more

- Microbiology: Rapid viral culture and bronchoscopic sampling

- Condition of recurrent infections due to dilated bronchioles and decreased mucociliary clearance --> Underlying muscle and supporting tissue is destroyed

- Often presents with hemoptysis --> May be life threatening

- Moderate or large amounts of purulent sputum produced daily

- Focal disease may progress to multilobar involvement

- History of severe childhood pneumonia or chronic, destructive inflammatory pulmonary disease

- Allergic bronchopulmonary aspergillosis

- Foreign body leading to chronic obstruction

- Alpha 1-antitrypsin deficiency

- HIV-infection

- Tuberculosis

- Rheumatoid arthritis

- Primary ciliar dyskinesia

- Hypogammaglobulinemia

- Pulmonary fibrosis

1. Acute exacerbation: Sputum culture-directed choice of antibiotics --> Often have resistant organisms

- Agressive pulmonary toilet to mobilize and expectorate sputum

- Assessment of severity of hemoptysis

2. Chronic management: Early treatment of infection

- Aggressive pulmonary toilet

- Cystic fibrosis: Defective cystic fibrosis transmembrane conductance regulator (CFTR) --> Autosomal recessive trait

- CF has multi-organ involvement --> Impaired epithelial chloride, sodium, and water transport

- CF patients produce profuse amounts of highly viscous mucus

- Diagnosis: Clinical history, elevated sweat chloride, 2 recognized CFTR mutations, and abnormal nasal potential difference

- Mucus clearance --> Chest PT and inhaled DNase

- Early recognition and treatment of infections --> Initially methicillin sensitive staph, then MRSA, then G- bacteria, then pseudomonas, and finally Burkholderia cepacia

- Infection with B. cepacia --> End stage CF

- Can determine staging and severity of disease based on the infecting pathogens

- Medications: Bronchodilators, aerosolized antibiotics, nutrition, monitoring of pancreatic function, and evaluation of bilateral lung function

- Recurrent partial or complete collapse of the upper airway during sleep, usually resulting in sleep fragmentation, cyclic hypoxemia, and hypercapnia

- Apnea-hypopnea index (AHI) >5 + symptoms= OSA

- Relatively high prevalence and highly underdiagnosed

- Central: Brain doesn't tell you to breath --> No muscle movement and no flow

- Obstructive: Muscle movement but no flow due to obstruction

- Mixed: Combination of central and obstructive pattern

- Lasts > 10 seconds with complete (>90%) cessation of flow and hypopnea

- Hypopnea: >50% decrease in flow with 3% desaturation and EEG arousal

- Mild: AHI >5

- Moderate: AHI >15

- Severe: AHI >30

- Age >60

- Male

- Post-menopausal women

- Family history

- Alcohol, opiates, sedating meds

- Supine position

- Nasal obstruction

- Neck circumference >17.5 inches or 40 cm

- Chronic lung disease

- African American, East Asian, and Pacific Islanders

- Craniofacial features

- Obstructive hypopnea-apnea --> Increased breathing effort

- Followed by arousal and hyperventilation

- Patient then returns to sleep and begins to hypoventilate due to upper airway collapse

- Obstructive hypopnea-apnea occurs again

- Day: Daytime sleepiness, fatigue, cognitive impairment of concentration, attention, and judgement, and morning headaches

- Night: Snoring, witnessed apneas, gasping arousals, restless sleep, insomnia and nocturia

- Neck circumference >40 cm/17.5 in

- Retrognathia --> Underbite

- Dental overjet

- Mallampati class: Determines how crowded the back of the throat is

- Oropharyngeal crowding

- Macroglossia

- Tonsilar hypertrophy

- ~50% predictive value with exam findings

- Screening: Asks patient how tired they are in different settings --> STOP BANG also

- Detects brain waves, flow, muscle contraction in the thorax, abdomen and body, and O2 sat

- Electrodes placed symmetrically on both sides of the body

- Two ways to detect flow, movement, etc

- Weight loss --> Biggest effect

- Oxygen --> Reduced/eliminates hypopnea

- Surgery --> Reconstruct upper airway and splint airway open --> Tonsillectomy in children and others in adults

- Oral appliances --> Mandibular advancement

- Positive airway pressure --> CPAP --> Helps eliminate hypopnea and keeps airway open

- Respiratory muscle training --> Playing the digeridoo

1. Cardiovascular: Hypertension, LVH/CHF, CAD, stroke, sudden cardiac death, and arrhythmia

2. Pulmonary: Pulmonary hypertension, and COPD

3. Diabetes and metabolic syndrome

4. Chronic kidney disease

5. Neuropsychiatric: Depression and mood disorders

6. Behavioral: Decreased quality of life

7. Cognitive: Decreased concentration and attention

8. Motor vehicle accidents --> Prevalence is very high

- ~50% of patients with OSA have hypertension

- ~30% of patients with hypertension have undiagnosed OSA

- OSA treatment quickly and markedly decreases hypertension

- 17% of patients with AHI >20 --> Mild PH

- OSA is a risk factor for PAH

- Daytime hypoxemia is typically seen in severe obesity-hypoventilation synrome and COPD

- Treatment with CPAP reduces capillary wedge pressures

- Often seen in CHF patients --> Decreased blood flow throughout the body results in reduced responsiveness by the carotid body

- Cheyne-Stokes respirations: Present in ~20% of CHF patients --> Crescendo-decrescendo ventilation

- Even present during the waking hours

- Other causes: High altitude periodic breathing (non-pathologic), narcotic induced ataxic breathing (Biot), and idiopathic central sleep apnea (RARE!)

- AKA Pickwickian Syndrome

- BMI >35, awake hypoventilation (PCO2 >45), worse during sleep with severe hypoxemia

- Often seen concomittantly with OSA

- Can result in PH, RV failure and erythrocytosis

- Impaired respiratory mechanisms due to obesity

- 10-20% of obese patients have OHS

- Impairment of hypoxic and hypercarbic ventilatory drive

- Rule out hypothyroidism, restrictive and obstructive lung disease before diagnosing

- Treatment: Weight loss, non-invasive positive pressure ventilation (BPAP) with or without O2

- Ondine's Curse --> Congenital mutation

- Elevated PCO2 during waking hours without neuromuscular, metabolic or lund disease

- No sensation of dyspnea

- Intact voluntary breathing control but patients will stop breathing if they stop thinking about it

- Treatment: Nocturnal ventilation with BPAP or 24 hour BPAP

- Hypothyroidism

- Neuromuscular disease

- Lung disease

- Spinal surgery

- CNS disease --> Medullary stroke, brainstem disease or tumor, meningo-encephalitis, Arnold-Chiari malformations and hypoxic encephalopathy

- Only genus of the family Mycobacteriaceae

- Slightly curved/straight bacilli with some branching

- High lipid content in cell wall --> Waves with mycolic acid

- Considered gram-positive but really G+ or gram-null

- Mycobacteria and some Nocardia

- Associated with the high lipid content in cell wall

- Allows for rapid differentiation

- Procedure:

1. Carbol fuchsin with phenol --> Penetrates and stains

2. Acid-alcohol decolorizing agent --> Primary stain remains in mycobacteria (acid-fastness)

3. Counterstain (methylene blue) applied --> Stains other bacteria blue

- Mycobacteria appears pink

- Pos stain: Indicates presence but sensitivity is low and specificity is high

- Heat fix specimen onto glass slide

- Flood slide with carbol fuchsin for 3 min and rinse

- Flood slide with 3% acid-alcohol for 3 min and rinse

- Counterstain with methylene blue for 1 min

- Rinse but do not blot dry

- Fluorochrome stain with phenolic auramine-rhodamine (acid-alcohol) and potassium permanganate counterstain

- Mycobacteria flouresce bright orange/yellow under a blue light source

- Advantage: Lab can screen many samples in a short time (20-40)

- Detects MTB complex genes --> 7 different species

- Also detects rifampin resistance

- Accurate test

1. Solid media

- Egg based and agar based

- Selective

- Relatively slow --> 8 weeks

- Growth enhanced by 5-10% CO2

2. Broth media --> Allows for more rapid growth

3. Lysis centrifugation --> Best for MAC from blood

- Decontaminate with N-acetyl-L cysteine and 1% sodium hydroxide and then centrifuge

- Direct processing if specimen not contaminated

- Rapid growers: 1-7 days --> M. chelonae, M. abscessus, and M. fortuitum

- Slow growers: More than 7 days up to 12 weeks --> MTB complex, M. avium complex, etc

- Intermediate growers: 7-10 days --> M. marinum and M. gordonae

- Most mycobacteria grow best at 35 C --> M. marinum likes 25-30 C and M. xenopi likes 42 C

- Consists of 7 different species --> All can cause tuberculosis

- 3 human pathogens: M. tuberculosis, M. africanum, and M. canettii

- 4 animal pathogens: M. microti (rodents), M. caprae (goats), M. bovis (bovine and human), and M. pinnipedii (seals)

- 1/3 of the world's population have been infected --> 2 billion people

- TB cases increased in the 80s with the apperance of HIV and decreased in government sponsored programs

- 13 countries account for 75% of all cases 

- 50 million people have drug resistant strains

- Leading cause of death in HIV-infected populations in developing countries

- Agar dilution method --> Growth >1% and takes 3-4 weeks

- Broth dilution method --> Any growth and takes 1-2 weeks

- Resistance to drugs does not appear to be genetically related

- Not associated with transformation, conjugation, transduction, transposition or plasmids

- Associated with chromosomal genes --> Passed down 1 at a time

- Primary resistance: Present prior to therapy

- Secondary: Emerges during therapy

- Isoniazid (10-8 - 10-9), rifampin (10-8), ethambutol (10-6), and streptomycin (10-5)

1. Multidrug Resistance TB (MDR-TB): Resistance to at least isoniazid and rifampin (most common) --> Other first line drug resistance also applies

- 1% of US cases

- Usually due to inappropriate treatment (non-compliance or wrong regimen)

- Requires specialized management

2. Extreme Drug Resistant TB (XDR-TB) --> Resistance to rifampin, isoniazin, any member of the fluoroquinolones and at least one of the injectable 2nd line drugs

- 2% worldwide

- Much higher mortality --> Very hard to treat

- Menace Law in MA may be used --> Involuntary hospitalization for patients putting community at risk

- Causes TB in cattle and other animals

- Acquired through drinking contaminated milk

- Attenuated strain, Bacillus Calmette-Guerin (BCG) used as a vaccine

- BCG vaccination or treatment can result in positive PPD --> Not recommended in the US

- Used as an adjuvant therapy for bladder cancer and carcinoma

- M. avium, M. intracellulare, and M. scrofulaceum

- Slow growers --> 10-28 days

- Opportunistic infections

- Disseminated disease in AIDS patients

- Pulmonary infections in people with chronic lung disease

- Infection from environmental sources (water)

- Treatment: Clarithromycin/azithromycin, rifabutin, etc

- Associated with chronic lung disease

- Rarely disseminates except in patients with AIDS or impaired cellular immunity

- M. fortuitum, chelonae, and abscessus

- Opportunistic infections --> Skin, soft tissue, skeletal, and catheter related infections, and some lung disease

- Treatment: Surgical debridement and clarithromycin with or without tobramycin and imipenem

- M. fortuitum --> Amikacin, cefoxitin, and probenicid

- Transmission: Soil or water contamination

- Opportunistic pathogen for humans, fish and reptiles

- Nodular localized infection at site of inoculation --> Fish Handler's disease

- Grows best at 30 C --> Takes 5-14 days

- Transmission: Fresh and salt water

- Treatment: Clarithromycin, minocycline or bactrim (SXT)

- Leprosy/Hansen's Disease --> ~192,000 cases worldwide

- Chronic debilitating granulomatous disease

- Anesthetic skin lesions and peripheral neuropathy with peripheral nerve thickening

- Primary site of inoculation and transmission: Nose

- Prolonged and intimate contact is required for transmission

- Natural hosts: humans and nine-banded armadillo 

- Incubation: 2-40 years --> Organism multiplies very slowly

- Symptomatic patients can have 10^15 bacilli

- Multiple presentations: Full tuberculoid (TT), borderline tuberculoid (BT), borderline (BB), borderline lepromatous (BL), and lepromatous leprosy (LL)

- Treatment: Paucibacillary (dapsone 100 mg daily and rifampin 600 mg monthly for 6 months) and multibacillary (dapsone 100 mg daily, clofazimine 50 mg daily, and rifampin 600 mg once a month for 2 years or more)

- Acid fast bacillus seen with a modifed AFB stain (Fite stain)

- Morphologic index (MI) used to assess % of viable cells in tissue

- Viable cells stain uniformly and brightly

- Dead cells stain irregularly

- Cannot cultivate in-vitro --> Grows in mouse footpads

- Grows best at cooler temps (<37C)

- Large, diverse group of G+ branched, filamentous bacteria

- Nocardia, Rhodococcus, Gordonia, and Tsukamurella

- Mycolic acids in their cell walls --> Stain weakly or partially acid-fast

- Nocardia most frequent!

- N. asteroides Complex (N. asteroides, farcinica, and nova)

- N. brasiliensis, N. otitidiscavarium, and N. transvalensis

- Chronic, suppurative and granulomatous infections

- Results in swelling and abscess formation and draining sinuses

- Most commonly in immunocompromised hosts

- Diagnosis: 2-5 days to grow on selective media, modified acid-fast stains and gram stains

- Treatment: Cutaneous (bactrim, minocycline or linezolid) and pulmonary/dissemination (Bactrim alone or imipenem with amikacin)

- Actinomyces sp. --> Facultative or anaerobic members of the normal flora of the mouth, colon, and vagina

- Tissue and abcess infections --> Formation of grains

- Polymicrobial infections (mix of anaerobes and aerobes)

- Most common: A. israelii, naeslundii, odontolyticus, viscosus, and meyeri

- Oral-cervicofacial

- Thoracic and disseminated disease

- Abdominal and pelvic disease (PID)

- CNS

- Musculoskeletal

- Periodontal --> Chronic disease that destroys gums

- Penicillin, amoxicillin or ampicillin --> High dose for complicated cases

- Surgical intervention

- Removal of IUD or prosthetic device (PID)

- Endemic in the world today --> Reservoir in infected persons

- Disease can involve any organ --> ~70% with lung involvement

- Spread from person to person (airborne) but not very contagious!

- Must have suspicion in order to diagnose

- TB is treatable and preventable

- Transmission: Source/environment, organism, and host all involved

- Pleomorphic, tend to clump and bead on acid-fast stain

- Staining only picks up ~40% of cases 

- TB cells travel down to the respiratory bronchioles and alveoli where they are engulfed by alveolar macrophages

- Macrophages then travel to the lymph nodes

- TB has learned how to evade killing by macrophages --> This is how it disseminates throughout the body

- Granulomas result in an attempt to control infection --> Granulomas can end up anywhere

- Primary pneumonia in ~10% of patients --> Mostly children <5 years and HIV patients

- Localized pneumonia --> Small lower lobe infiltrate with hilar node enlargement (Ghon Complex) on CXR

- Must get lateral CXR to diagnose in children <11 years

- ~90% of patients can contain for lifetime

- Organism is successfully enclosed within granulomas

- Replication time is extended --> >>>20 hrs

- May lose staining properties in granulomas

- Granuloma environment: Low PO2, reduced CHO, and high fat content

- Risk of reactivation --> 10% with 2-5% in the first 2 years after infection

- Standard Tuberculin Skin Test --> Subcutaneous injection of 0.1 mL PPD

- Must be read within 48-72 hours after implantation by a trained professional

- Positive PPD: >5 mm in immunocompromised people, close contact with TB case, and CXR lesions, >10 mm for high incidence  groups and recent PPD converters, and >15 mm for everyone else

- Bacille Calmette-Guerin

- Live-bacteria vaccine

- Given to many children in parts of the world where TB is a huge problem

- Good at preventing severe disease in children

- BCG may cause a positive PPD 

- If TB test is positive --> Patient likely has TB regardless of vaccination!!

- In-vitro assay used to diagnose TB infections

- Requires blood draw

- Measures circulating IFN-g released by T-cells following stimulation with TB antigens

- Includes positive and negative controls

- IFN-g levels determined with ELISA

- MTB complex specific antigens used

- Positive PPD

- Symptoms: Cough, fevers, sweats, weight loss

- Abnormal CXR

- Contagious

- Treat with multiple drugs

- 9 mill cases/year world wide

- ~10% of infected patients reactivate to active TB

- Recent infection --> First 2 years

- HIV/AIDS --> 7-10%/year

- Co-morbidities: Diabetes, steroid therapy, rapid weight loss, ESRD, lymphatic/hematologic malignancies

- Age: <4 years and elderly

- Symptoms: Cough, chest pain, fever, weight loss, night sweats, and fatigue --> May be asymptomatic

- Epidemiology: Travel history, contacts, and country of origin

- CXR

- Labs: Smear, culture, and molecular

- Initial diagnosis is clinical --> Based on suspicion

- Reportable disease --> Report to state DPH --> Patient centered case management

- Multiple medications --> Usually 4 drugs to start (INH, rifampin, pyrazinamide, and ethambutol)

- Close clinical and lab monitoring (monthly)

- At least 6 months of treatment --> May require years

- Commitment to treat patients with disease --> State TB clinics and other specialized care

- Lifelong TB risk if PPD+ --> Highest risk for first 2 years

- Medications kill dormant tubercle bacilli

- 9 months of Isoniazid or 4 months of rimapin treatment

- Side effects must be monitored

- Reduces the rist of developing active TB by >90%

- Trying to develop shorter, effective regimens

- 12 week therapy

- LTBI thought to be due to recent exposure to contagious TB

- Conversion from negative to positive PPD (TST converion or INF-g release)

- Radio-graphic findings of healed pulmonary TB --> Must first rule out active TB

- Healthy HIV-infected patients

- Helical capsid with - sense ssRNA genome with viral RNA polymerase

- Released by budding --> Assembly at the membrane by matrix protein

- Ubiquitous --> Everyone is infected by age 5

- Transmission: Person-to-person and fomites

- Serotypes: PIV-1,2,3,4

- Pathogenesis: Replicates in respiratory tract epithelium --> Syncytia formation, cell death, and inflammatory response leads to symptoms

- Re-infections are common but usually less severe than 1st exposure

- Incubation: 2-6 days

- PIV-1-PIV-4 cause mild to severe respiratory disease

- PIV-1 and PIV-2 --> Croup but PIV-1 more severe

- PIV-3: Pneumonia and bronchiolitis in <6 month olds

- PIV-4: Mild URT infections

- Most common in children 6-36 months and boys

- Most common in the fall/winter months

- ~33,000 hospital admissions

- Laryngotracheitis: Inflammation of the trachea and larynx --> Subglottal swelling can obstruct airway

- Symptoms: Instratory stridor and "seal bark" cough

- Laryngotracheobronchitis: Inflammation extends into the bronchi (LRT) --> Wheezing, rales, air trapping, and increased tachypnea

- Diagnosis: Usually clinical but lab tests are possible

- Treatment: Supportive, no antivirals, glucocorticoids and nebulized epinephrine may be used

- Prevention: No vaccine so infection control is crucial

- - sense ssRNA with helical capsid and envelope

- Ubiquitous and very contagious --> Almost everyone infected by 2 years

- Transmission: Contaminated hands, fomites, and respiratory droplets

- Serious outbreaks in pediatric wards and NICUs

- At risk: Most serious disease in premature infants

- Most common cause of LRTI in children <1 years old

- Estimated 2,700 adult and pediatric deaths/year

- Replicates in epithelial cells in the respiratory tract --> Includes terminal bronchioles (LRT)

- Tissue damage: Due to syncytia formation, cell death, and immune response (CMI response)

- Airways become obstructed by edema, mucus, sloughed epithelial cells, and necrotic material

- No long-term protection --> Both Ab and CMI responses

- Two subtypes --> A&B

- Incubation: 4-6 days

- Mild to severe respiratory disease

- Most common cause of bronchiolitis in infants

- Symptoms: Increased respiratory effort, expiratory wheezing in children <2 years, atelectasis, and apnea in <2 months

- Diagnosis: Usually clinical but lab tests possible

- Treatment: Ribavirin --> Mixed results in patients and palivizumab to prevent severe infection and disease

- Treatment ultimately depends on the patient and severity of disease

- Prevention: No vaccine so infection control is crucial --> Contact precautions

- - sense ssRNA with helical capsid and envelope

- Ubiquitous and very contagious --> Almost everyone infected by 5 years

- Many flu and pneumonia cases may actually have been caused by this

- Transmission: Hands, fomites, and respiratory droplets

- Pathogenesis: Not well understood but probably similar to RSV --> Replicates in epithelial cells of respiratory tract

- Infection associated with inflammation, lots of mucus, and hyperplasia of epithelium --> Airway obstruction

- Re-infection and recurrence is common

- Possible link between this virus and asthma/wheezing later on in life

- Incubation: 3-5 days

- Usually associated with mild, self-limited infections in adults and children --> URT infection

- Severe disease involving LRT can occur and may require hospitalization

- Diagnosis: Usually not definitively diagnosed --> Similar to other respiratory infections, lab tests available but not standardized

- Treatment: Supportive and depends on severity

- Prevention: No vaccine so infection control is important --> Contact precautions

- Enveloped but tough with helical capsid and non-segmented + sense ssRNA genome

- Released by exocytosis

- Transmission: Respiratory route but in some cases fecal-oral route

- Pathogenesis: Not well understood but most infections are respiratory

- Immunity is transient --> Re-infection common

- 2nd most frequent cause of the common cold

- Caused by SARS-CoV --> Began in the Guangdong Province in China

- Transmission: Droplet secretions, fomites and person-to-person

- Some patients can be "superspreaders" that can transmit to MANY other people

- Reservoirs: Bats and civet cats

- Good hygiene to prevent transmission

- No vaccine or anti-virals

- ~200,000 hospitalizations/year

- ~20,000-40,000 deaths/year

- 90% of those deaths are >65 years

- Severe epidemic can cause $15 billion

- Types: A, B & C

- Glycoproteins: Hemagglutinin and Neuraminidase

- Genome: 8 ssRNA segments --> ~13 genes

- Surface proteins: M1 and M2 matrix proteins, nucleoprotein (NP), polymerases PB1, PB2, and PA, NS1 (transcripton factor) and nuclear export factor

- Hemagluttinin is equally spaced over the surface of the envelope --> Binds to cell surface receptors and allows for attachment

- Neuraminidase tetramers cluster in groups --> Facilitate release

- Matrix protein located just under envelope

- Nucleocapsid and matrix proteins are wrapped in host cell membrane as they are released by budding

- Replicates in nucleus

- Transmission: Respiratory droplets and airborne, incubation (1-4 days), and replication in the respiratory epithelium

- Clinical presentation: Abrupt onset of fever, chills, muscle aches, headache, sore throat, and non-productive cough

- Symptoms last ~ 1 week

- Antibodies develop during 2nd week

- Virus is shed for 5-7 days during infection and a day before infection begins

- Abnormal tracheobronchiolar clearance, airway hyperactivity, and small airway dysfunction

- Post-influenza asthenia: Severe malaise, lassitude, and cough that persists for several weeks --> Up to 4 weeks

- Respiratory complications: Influenza pneumonia, secondary bacterial pneumonia, and otitis media in children

- Others: Exacerbation of underlying medial conditions, Reyes syndrome, myositis, rhabdomyolysis, myocarditis, pericarditis, aseptic meningitis, and encephalitis

- Presumptive --> Due to symptoms

- Definitive --> Virus is easily isolated from the throat and nose via cell culture, immunoflourescence, RT-PCR, and serology (less useful)

- Differential: Enterovirus, RSV, adenovirus, parainfluenza virus, and coronavirus

- Type A --> Moderate to severe illness, animals and humans, and all age groups

- Type B --> Milder illness, humans only, and primarily in children

- Type C --> Mild illness, humans only, and not associated with epidemics

- 16 hemagglutinin types and 9 neuraminidase types

- Nomenclature: Type/Infected animal/Site of isolation/Strain #/ Year/ Subtype

- Responsible for seasonal epidemics

- One or more influenza A subtype and B viruses circulating

- Small mutations in HA or NA --> New strains

- Some population immunity --> Extent of immunity determines severity of epidemic/pandemic

- Everyone needs a new vaccine every year

- Possibility for pandemic influenza

- Change to a different HA or NA subtype --> New viral subtypes

- Happens if two strains of the virus infect the same host and reassortment occurs

- Also happens if there is a direct species jump

- Minimal population immunity is present --> More severe disease

- Match between strains in the vaccine and strains circulating in the community

- Look at the strains circulating through South America and Asia since their seasons are 6 months before ours

- Helps host immune response

- May not prevent infection but reduces severity and mortality

- Due an antigenic shift event

- Occurs when a new subtype presents itself to the human population

- Must spread to other countries and each outbreak must last >2 weeks

- Overall cycle lasts two years

- Severity depends on the virulence, rapidity of spread, effectiveness of prevention and extent of population immunity already present

- Spanish Flu (1918): 20-40% of world's population infected and 20-40 million died (2.5% mortality rate) --> 20x death rate in 15-34 year olds

- H1N1 outbreak starting in Fort Dix, NJ

- Vaccine developed from this outbreak --> 45 million doses administered

- Important because incidence of Guillem-Barre increased dramatically due to this vaccine

- Avian Influenza Outbreaks in Humans (1997) --> Worrisome and dangerous if reassorted virus reassorts again with a more virulent and severe animal virus

- H1N1 Pandemic (2009-2010)

- H5N1 and H7N9 Pandemic (2013) --> Currently very few human cases and mostly only in humans but the risk for species jump is high and scary!!

- Either trivalent or quadrivalent --> Adds an extra B type

- Inactivated, live-attenuated, cell culture and recombinant vaccines available

- All available in trivalent or quadrivalent forms

- Don't prevent infection but reduce severity and mortality

- Amantines are no longer useful --> Target M2 matrix protein

- Neuraminidase inhibitors (oseltamivir and zanamivir) --> Inhibits the release of the viruse from the infected cell and has activity against Type A and B

- Neuraminidase inhibitors would need to be taken for long periods of time to successfully treat and prevent infection with influenza strains --> Not realistic

- Best thing is to isolate cases and teach respiratory hygiene and cough etiquette

- Also, wear masks in public places if you or someone around you is sick!!

- Typical --> Bacterial Pneumonia

- Symptoms: Fever, productive cough and sputum, chills, SOB, and pleuritic chest pain

- Atypical symptoms: Extrapulmonary symptoms (GI symptoms --> Due to Mycoplasma, Legionella, Chlamydia, Rhinovirus, Influenza, and Parainfluenza

- More gradual onset for atypical symptoms

- Treatment: Azithromycin/erythromycin or doxycycline to cover S. pneumonia and other atypicals

- Mycoplasma pneumoniae

- Legionella pneumophila

- Chlamydia pneumoniae

- Viral --> Rhinovirus, influenza, and parainfluenza

- Gradual onset of symptoms --> CXR worse

- Treatment: Fluoroquinolone (levofloxacin) or a B-lactam and azithromycin/erythromycin --> More broad to cover the atypicals and G- rods

- Rates how badly a patient needs to be admitted to the hospital

- Age >65

- Nursing home resident

- Co-existing illnesses --> Malignancy, chronic renal failure, cirrhosis, CHF, and CVA

- Physical findings: Tachypnea, tachycardia, hypotension, hypo/hyperthermia, and confusion

- Non-ICU patients

- S. pneumoniae, viruses, H. influenzae, atypicals, polymicrobials

- Treatment: 3rd generation cephalosporin (ceftriaxone) and azythromycin/erythromycin or fluoroquinolone (levofloxacin) 

- Pneumonia that developed in a non-hospitalized patient with extensive health care contact

- Nursing home residents, IV therapy or HD in last month, or hospitalization in the past 3 months

- Need to consider multi-drug resistant organisms --> Particularly MRSA and gram negative rods

- Major criteria: Respiratory fiaulre requiring ventilation or shock requiring pressors

- Minor criteria: Multi-lobar infiltrates, respiratory rate >30, hypotension, leukopenia, thrombocytopenia, hypothermia, and confusion

- Also pH <7.3 increases sensitivity for minor criteria and is a good indicator of whether pt should be admitted

- S. pneumoniae, Legionella, MRSA, and gram negative rods (Pseudomonas)

- Treatment: Cefoxatine and azithromycin or levofloxacin

- Empiric treatment for Pseudomonas and Staph aureus is necessary

- Presents 48-72 hours after intubation or longer

- Need to consider the anti-microbial profile of the hospital

- Need to cover for MRSA and virulent gram negative rods

- Treatment: Vancomycin or linezolid and anti-pseudomonal meds (Cefepime, meropenem, and piperacillin/tazobactam) 

- Pseudomonas aeruginosa is the most common

- 6-10% of cases overall --> Rarely in healthy people

- Risk factors: Neutropenia, CF, chronic trach patients, late stage HIV, and bronchiectasis

- 3-5% of cases

- Moraxella catarrhalis

- Strep. pyogenes --> Often very severe and requires ICU

- Neisseria meningitis (G-) --> Usually a cause of meningitis

- Usually due to aspiration pneumonia

- Also usually due to the fact that patients have poor dentition and lots of bacteria in the gingival crevices

- Pneumonitis occurs but necrosis begins after 1-2 weeks

- Empyema may form after abcess

- Due to aspiration of oral flora

- Usually poly-microbial and anaerobes predominate

- Organisms: Peptostreptococcus, Prevatella, Bacteroides, and Fusobacterium

- Treatment: Clindamycin --> Need to treat for 3-4 weeks

- Purified capsular polysaccharide from the 23 serotypes that cause 85-90% of infections

- Produces an antibody response that lasts up to 10 years

- Should be given to patients >65 or those with chronic illnesses (COPD, CHF, diabetes, alcohol abuse, cirrhosis, or asplenia)

- Repeat vaccination after 5-10 years in patients >65

- Chest X-ray

- CT scan 

- Suspicious for lung cancer: Any non-calcified nodule >4 mm on CT scan OR any non-calcified nodule/mass classified as positive on CXR

- Stable abnormalities over 3 studies could be reclassified as minor abnormalities 

- 20% relative risk reduction with CT scan over CXR --> 320 people must be scanned to save one

- High false-positive rates --> 96.4% --> Only ~4% actually have lung cancer

- Causes unnecessary patient anxiety and unnecessary costs/harms

- Cumulative effects of radiation exposure over time --> Equivalent to 15 CXRs or 50 cross country flights

- Financial burden

- Over-diagnosis!!

- US Preventative Services Task Force recommends for screening high risk populations, NOT everyone

- Solitary opacities completely surrounded by lung parenchyma and not associated with hilar enlargement/atelectasis

- Nodules: Less than <3cm

- Masses: >3 cm --> More likely malignant

- Sub-centimeter nodules: <8 mm in diameter --> Less likely to be malignant

- Can be non-solid, solid or part solid

1. Bronchogenic Cancers: Adenocarcinoma, squamous cell, large cell and small cell

2. Metastatic: Breat, Head & Neck, melanoma, colon, kidney, sarcoma, germ cell, and carcinoid

- Often present as larger masses that are not smooth --> Often spiculated 

1. Granulomatous diseases (80%): Histoplasmosis, coccidioimycosis, TB, atypical mycobacteria, bacterial abcess, dirofilaria immitus, echinococcus cyst, ascariasis, PCP, and aspergilloma

2. Developmental: Bronchogenic cyst

3. Inflammatory: Wegner's granulomatosis and Rheumatoid nodule

4. Soft Tissue: Hamartoma (10%), lipoma, fibroma, rounded atelectasis, amyloidoma, intrapulmonary lymph node, hematoma, pulmonary infarction, pseudotumor, and mucoid impaction

5. Vascular: AV malformation and pulmonary varix

- Smoking history: Current or past

- Hemoptysis

- Previous cancers

- Age --> 3% risk for 35-39 year olds and 50% or higher likelihood >60 years

- Screening is important because malignant nodules represent a potentially curable lung cancer

- Nodules were identified in 8-51% of patients

- Prevalence of malignancies in these nodules --> 1.1-12%

1. Nodule size: <5 mm (0-1%), 5-10 mm (6-28%), and >2 cm (64-82%)

2. Border edges --> Smooth (20-30%) and irregular, lobulated, or spiculated (30-100%)

3. Morphology: Pure ground glass (59-73%), partially solid and non-solid (32%), and solid (7-9%)

- Upper lobe nodules have a higher incidence of being malignant

- 84% of cavitary lesions with a wall greater than 15 mm in thickness were malignant

4. Patterns of calcification: Diffuse, central, popcorn, and laminar (benign) and stippled or eccentric (malignant)

5. Volume doubling time --> The slowest and fastest growing nodules are usually not malignant

- Low suspicion (<0.12) --> Wait and watch

- Intermediate suspicion (.12-.69) --> Indeterminate

- High suspicion (.69-.90) --> Surgery or biopsy

- Highest suspicion (>.90) --> Surgery immediately

- Good idea to perform a PET scan, TTNA, or bronchoscopy for indeterminate suspicion --> Decreases the number of patients getting unnecessary surgery by 15%

- Stable on serial CXR for 2 years with the exception of sub-centimeter numbers and GGO

- Characteristic benign calcification pattern

- Present in patients <35 years old in the absense of other risk factors

- 80% caused by granulomatous diseases and 10% by hamartomas

- Doubling time is usually <1 month or >16 months (slowest or fastest)

- Only recommended for patients with indeterminate CT scans

- Sensitivity: 80-100%

- Specificity: 60-90%

- False positives: Due to metabolically active infectious or inflammatory lesions

- False negatives: Small tumor size, relatively low tumor metabolic activity (bronchoalveolar tumors, etc), or due to uncontrolled hyperglycemia

- Used to obtain a sample from a peripheral lesion

- Not good for central lesions

- Guided using fluoroscopy

- True positives: 60% with lesions >2 cm

- False negatives: 20-30% of patients

- Diagnostic yield for benign lesions --> 12-68%

- Used to take a sample of centralized lesions

- 60-70% yield for peripheral lesions >2 cm

- 70% yield for all central lesions

- 90% yield for a central lesion that is visible

- Guided by fluoroscopy or ultrasound

- Ultrasound allows for visualization of smaller lesions

- <4 mm: No follow up for low suspicion and 12 month follow up for high suspicion

- 4-6 mm: 12 m follow up for low suspicion and initial 6-12 month followed by 18-24 month follow up for high suspicion

- 6-8 mm: 6-12 month followed by 18-24 month follow up for low suspicion and 3-6 month, then 9-12 month, and 24 month follow up for high suspicion

- >8 mm: 3,9, and 24 month follow ups for low suspicion and 3,9, and 24 month follow up for high suspicion

- Occlusion of the pulmonary arterial system with a foreign substance

- Causes: Blood clot (most common), cholesterol crystals, amniotic fluid, air, neoplasm, foreign bodies, and parasites

- Prevalance: 600,000 cases/year in US, 5% mortality in treated cases and most common cause of sudden death in hospitals

- Sources of emboli: Iliac-pelvic veins, femoral veins, calf veins, and upper extremity central veins (less common)

- Virchow's Triad

- Injury: Damage to venous wall --> Inflammation, etc

- Stasis: Cessation of blood flow through the venous system

- Thrombophilia: Blood hypercoagulability

- Genetic: Anti-thrombin III, Protein C, Protein S, etc mutations

- Hospitalization for acute medical illness

- Post-op

- Immobilization

- Malignancy --> These patients bleed ALOT

- Burns

- Neurologic injury/stroke

- Increasing age

- Pregnancy

- Exogenous estrogen

- Anti-phospholipid syndrome

- Nephrotic syndrome

- Dead Space: Ventilated but not perfused

- Atelectasis: Results in V/Q mismatch and elevated A-a gradient

- Shunt: Blood is shunted away from the occluded vessel --> Leads to increased A-a gradient

- Criteria used to determine whether a patient needs to be treated

- Clinical symptoms of a DVT (3 points)

- Alternative diagnosis less likely (3 points)

- HR > 100 (1.5 points)

- Immobilization > 3 days or surgery in last 4 weeks (1.5 points)

- Previous PE/DVT (1.5 points)

- Malignancy (1 point)

- Hemoptysis (1 point)

- Symptoms: Dyspnea, pleuritic chest pain, cough, apprehension, sense of heart pounding, signs of DVT, or asymptomatic

- Exam: Tachypnea, tachycardia, low grade fever (<101), pleural effusion, pleural rub, localized crackles or dullness, wheezes, loud P2, signs of DVT, and signs of RVF

- Labs: Increased A-a gradient, D-dimer, BNP, and Troponin I/T

- ECG: Non-specific ST/T wave changes, arrhythmias,  new Afib, right axis deviation, S1Q3T3, RBBB, and P-pulmonale

- CXR: Often normal but can see atelectasis, pleural effusion, oligemia (hypoperfusion), hemi-diaphragm elevation, asymmetry of pulmonary arteries, loss of lobar artery, and Hampton's Hump (infarct)

- Leg ultrasound --> Looking for DVT in the legs as source --> Negative result doesn't rule out PE

- Echocardiogram --> Might show RVF and actue PAH

- Ventilation/Perfusion Scan

- CT pulmonary angiogram

- Invasive pulmonary angiogram

- Injection of radioactive technitium

- Inhalation of radioactive xenon

- Normal result rules out PE

- Useful for low and high probability results

- Not helpful for intermediate result

- Advantages: Rules out PE if normal, non-invasive, minimal risk, sensitive for peripheral emboli, and can be performed on patients with renal impairment

- Disadvantages: Non-specific findings are common and less useful for patients with pre-existing lung disease

- Injection of contrast into pulmonary artery

- Advantages: Easy to perform, high specificity (80-100%), sensitive for moderate sized emboli, and useful for pre-existing lung disease

- Disadvantages: Radiation exposure, sensitivity for small peripheral emboli unknown and contrast is a nephrotoxin

- Gold standard test

- Required in less than 10% of cases

- Always abnormal if clinically significant emboli is present

- Indications: Confirm diagnosis and in patients with contraindications for anticoagulation

- Advantages: Specific

- Disadvantages: Invasive, requires contrast, requires experienced personnel, and significant risk of complications

- Un-fractionated heparin (UFH) or low molecular weight heparin (LMWH)

- LMWH is preferred except in the morbidly obese, renal failure patients, and hypotensive patients

- Thrombin inhibitors: Used when heparin contraindicated

- IVC Filter: Not indicated unless patient has contraindications for anticoagulants, allergy to medications, or at high risk of re-infarction

- Thrombolytics: No indicated

- Unstable: Unable to be oxygenated or are hemodynamically unstable

- Heparin --> Unfractionated

- Thrombolytic agents --> Only indicated if patient does not have any other active bleeding or risk of active bleeding

- IVC filter: May be used in patients with a residual DVT

- Determine reversible causes if they exist --> Treat these

- Treat with oral anti-coagulants --> Warfarin unless pregnant then heparin

- Conditions requirely life-long therapy: Antiphospholipid syndrome, malignancy, second clot, and previous massive PE

- Heparin is more effective than warfarin for cancer patients

- 

- Complete recovery

- Death

- Chronic Pulmonary Vascular Disease --> Chronic thromboembolic pulmonary disease, pulmonary hypertension, and cor pulmonale/right heart faiulre

- Pathogenesis: Incomletely resolving emboli, diffuse vascular remodeling, and pulmonary hypertension

- Presentation: Chronic symptoms of dyspnea on exertion, fatigue, syncope, and lower extremity edema

- Right Heart Cath: Elevated RV pressures, central thrombus, and narrowing of pulmonary vessels

- Treatment: Anticoagulation (heparin/warfarin), IVC filter, and surgical thromboarterectomy in proximal disease

- Prevention: Either inpatient or outpatient --> Exercise, heparin/warfarin, and pneumatic pressure stockings 

- Looks like millet seeds on CXR

- Smallest possible nodular pattern

- Nodules all over the lung

- Caused by tuberculosis infection

- Clearly seen on CT scan but can be seen on CXR too

- Clearly demarcated, grey, and grainy looking

- Implies that an interstitial and alveolar microscopic process is occuring

- Causes: Cancer (mostly LL), DIP, infection, pulmonary edema, chronic eosinophilic pneumonia (CEP), hypersensitivity pneumonia (HP), DIP, etc

- Needs a biopsy to determine cause

1. Alveolar: Cloudy appearance --> Air bronchograms

- Pneumonias 

2. Interstitial: Criss-crossing lines and Kerley B lines

- Pulmonary fibrosis (UIP, DIP, NSIP, HP, etc) --> Interstitial lung disease

- Pulmonary edema

- Sarcoidosis

1. Cardiogenic: Airspaces are filled will fluid but lung structures are still intact --> Caused by changes in hydrostatic pressure

2. Non-cardiogenic: Airspaces filled with fluid and hyaline membranes due to lung injury and degradation --> Due to increased permeabiilty of the lung membrane

- Bilateral infiltrates

- Costo-phrenic angles are spared bilaterally

- Interstitial pattern seen

- Lung injury, cell damage, and respiratory failure

- Potential Agents: Shock, inhaled toxins, trauma, aspiration, infection, drugs, DIC, uremia, radiation, and embolism

- Pathogenesis: Begins at either the endothelium or epithelium --> Increased permeability and barrier breakdown --> Extravasation of cells and plasma --> Edema and hemorrhage leading to increased surface tension

- Results in wet, atelectatic lung --> Hypoxemia, stiff lung, and diffuse infiltrates

- Injury --> Alveolar macrophage activation --> PMN amplification

- Leads to ROS formation

- ROSs reduce the lipids in surfactant --> Toxic to lung tissue

1. Insult within past 7 days or new/worsening respiratory symptoms

2. Bilateral opacities on CXR/CT that is unexplained by effusion, collapse or nodules

3. Edema unexplained by CHF or volume overload

4. Oxygenation: PaO2/FiO2 ratio

- Normal: 500, mild: 300-200, moderate: 200-100, and severe: <100

- Assist with work of breathing --> Increases with ARDS

- Respiratory muscle Vo2 3% to >25%

- Work of breathing increases due to muscle fatigue

1. Wb assistance: PEEP and provide mechanical ventilation

2. PaO2 management

3. Metabolic abnormalities

4. Treat infections

- Increases in FRC

- Increased compliance

- Decreases work of breathing

- Opens collapsed lung units

- Decreases intra-alveolar shunt

- Increases PaO2 and decreases FiO2

- Increasing PEEP allows for decreased O2 delivery --> Avoid oxygen toxicity

- Higher PEEP --> Lower FiO2 and Lower PEEP --> Higher FiO2

- Need to maintain PaO2 at 60 mmHg

- O2 + PEEP + prone position? + NO?

- Prone position is helpful early on --> Distributes edema around the lung and reduces toxicity to particular areas of the lung

- NO --> Potent vasodilator but can be toxic by producing ROSs

- Transfusions: Increase Hb content --> Can cause transfusion lung injury so want to avoid giving alot!!

1. Correct metabolic abnormalities: Electrolytes, BUN, creatinine, coagulation, glucose, and nutrition

2. Treat infections: Can be either the cause or result of ARDS

- Pt comes in with sepsis and then develops ARDS --> Source in abdomen

- Pt comes in with ARDS and then develops sepsis --> Source is lung

- Barotrauma

- Infection (VAP)

- Swan-Ganz catheterization complications --> Not recommended

- Acute phase: Not used

- Fibro-proliferative phase: No support either

- Decreases the amount of ventilator days and no increases in infection

- No mortality benefit --> Bad after 14 days

- May actually be helpful for fat embolism though

- Mortality: Now 30% but was >50%

- Symptoms for Early ARDS survivors: Few symptoms, mild, and decreased PFT-gas

- Symptoms for Late ARDS survivors: Increased lung abnormalities and increased non-lung morbidity

- High association between alcoholism and development of ARDS

- Alcohol --> Reduces glutathione production in Type 2 pneumocytes and hepatocytes --> Reduced glutathione reduces that ability of the lung to neutralize ROSs

- Give cysteine supplements to alcoholics might reduce the incidence

- Normal amounts of pleural fluid: 15 cc

- Function: Lubrication and transition of chest wall forces 

- Pleural space: 10-20 um

- Pleural fluid --> Ultrafiltrate from blood --> Produced via Starling forces (hydrostatic and oncotic pressure)

- Produced and resorbed at a constant rate by parietal fluid

- Liver disease and nephrotic syndrome --> Low oncotic pressure --> Effusion

- Abnormal accumulation of pleural fluid within the pleural cavity

- Associated with many different diseases

- Symptoms: Progressive SOB, pleuritic chest pain, decreased breath sounds, dullness to percussion, and decreased fremitus

- CXR: Meniscus sign seen and gradient of opacities

- Lateral decubitus, CT scan or ultrasound used to determine if effusion is really present

- CXR detects 250cc, lateral decubitus view detects 50cc, CT scan detects 50-20cc, and ultrasound detects 20cc

- Procedure where a needle is placed just above one rib into the pleural space

- Must be careful to not puncture the visceral pleura

- Also must be sure there is enough fluid to actually aspirate

- If too little fluid is left --> Re-expansion pulmonary edema

- Fluid analysis performed: Color/clarity, cellularity, pH, cytology, protein and ANA (rheum.)

- Red: Malignancy, post-asbestos pleural effusion (PAPE), PCIS, pulmonary infarction and trauma

- White: Chylothorax, pus or empyema

- Nucleated cells: ~1700 cells/mL

- Macrophages: 75%

- Lymphocytes: 23% --> Increased in TB, lymphoma, sarcoid, rheumatoid, and chylothorax

- Mesothelial cells: 1% --> >5% excludes TB

- PMNs: <1% --> >50,000 PMNs --> Infection

- Eosinophils: <1% --> >10% in BAPE, blood/air in pleural space, some cancers, and fungal infection

- RBCs: ~600 cells/mL --> Very high in hemothorax and PE

- Normal= 7.6

- Decreased <7.2 --> Infection, malignancy, esophageal perforation, RA, and lupus

- All unknown effusions should be sent for cytologic analysis

- Cell block made from 500cc of fluid

- Flow cytometry occassionally helpful

- Protein

- LDH

- Glucose

- Amylase

- Cholesterol/triglycerides

- Determines transudate vs. exudate

- Transudate: Bland, non inflammatory, imbalance of hydrostatic/oncotic forces, and low protein, cell counts, and chemistry values

- Exudate: Inflammation and impaired lymphatic drainage --> High protein, cell counts, and chemistry values

- Pleural fluid/serum protein ratio >0.5

- Pleural fluid/serum LDH >0.6

- Pleural fluid LDH greater than 2/3 upper limit of normal (around 250)

- Other criteria: Cholesterol >45 and pleural fluid protein >2.9 g/dL

- CHF --> Effusion can convert to exudate with the use of diuretics!!

- Hepatic hydothorax

- Nephrotic syndrome

- Peritoneal dialysis

- Low albumin state

- Urinothorax

- Atelectasis

- Constrictive pericarditis

- Trapped lung

- Duro-pleural fistula

- CVC leak

- SVC obstruction

- Infection

- Malignancy

- Hemothorax

- Chylothorax

- Pancreatitis

- Esophageal perforation

- Connective tissue diseases

- PE

- Post-cardiotomy

- Uncomplicated: negative microbiology, pH >7.20, and cell count ~10,000

- Complicated: Cell count ~50,000, pH<7.20, LDH high, glucose low, gram stain/cx somtimes positive

- Empyema: pus in pleural space, pH <7.20, cell cound ~100,000, positive gram stain, and glucose low

- Rupture of caseous focus --> DTH reaction

- Most commonly presents as acute illness 

- Usually unilateral

- Most are culture negative

- May consider pleural biopsy

- Milky white fluid --> Only present in 58%

- Pleural fluid triglyceride level greater than 110 mg/dL

- Causes: Thoracic duct blockage from trauma, cancer or LAM

- Lung

- Breast

- Ovary

- Lymphoma

- Metastatic disease

- Mesothelioma

- 60% of effusions that occupy 2/3 of hemithorax are malignant

- Multiple mechanisms: Post-obstructive and pleural mets

- Very poor prognosis!!

- Patients must be symptomatic with improvement after thoracentesis

- Options for management: Chemo, repeated thoracentesis, Heimlich valve, tube thoracostomy, throacoscoy, tunneled long-term catheter, and pleuro-peritoneal shunts

- Primary: Can happen to anyone but usually in tall and skinny individuals --> Good prognosis

- Secondary: Due to lung disease

- Traumatic

- Iatrogenic: Health care induced

- Tension: Medical emergency, air accumulates with a one-way valve, compresses the lungs and mediastinum, tachycardic, hypotensive and cyanotic --> Needs to be immediately decompressed

- Treatment: Oxygen, simple aspiration or chest tube

- Mean PAP >25 mmHg at rest with normal LV function (PCWP <15 mmHg) and PVR 240

- Previously defined as primary or secondary but now the categorization is different

1. Idiopathic

2. Hertiable --> BMPR2, ALK-1, and endoglin

3. Drug/toxin induced --> Diet supplements (Fen-Phen), cocaine, and meth

4. Associated with (APAH) --> Connective tissue disease, HIV, portal hypertension, congenital heart disease, schistosomiasis, and chronic hemolytic anemia

5. Persistent pulmonary hypertension of a newborn

1. PAH

2. Pulmonary hypertension owing to left heart disease --> Systolic or diastolic dysfunction and valvular disease

3. Pulmonary hypertension owing to chronic lung disease/hypoxia --> COPD, ILD, sleep apnea, alveolar hypoventilation disorders, chronic exposure to high altitude, developmental and other

4. Chronic thromboembolic pulmonary hypertension (CTEPH)

5. Pulmonary hypertension with unclear multifactorial mechanisms --> Hematological disorders, systemic disorders, metabolic disorders, and other

- Endothelial/intimal thickening --> Proliferation

- Smooth muscle proliferation, ECM and elastin proliferation

- Smooth muscle cell migration and neointima formation

- Characteristic plexiform lesion can be seen

- True etiology unknown

1. Vasomediator imbalance: Increased endothelin and serotonin and low NO and prostacyclin levels

- Endothelin and serotonin --> Vasoconstrictors

2. Ion-channel activity defect --> Newly determined K+ channel involvement

3. Inflammation

4. Dysregulated angiogenesis

- Environmental factors along with genetic predisoposition leads to the development of PAH

- Genetic mutations all display incomplete penetrance and anticipation

1. Ingested substances: Appetite suppressants, monocrotaline, rapeseed oil, L-tryptophan, methamphetamine, and cocaine

2. Hypoxia

- Connective tissue diseases --> Scleroderma (10% of SCL pts)

- HIV infection

- Portal hypertension (cirrhosis)

- Congenital heart disease

- Hemoglobinopathies (sickle cell/B-thallassemia)

- Schistosomiasis

- Bone morphogenetic protein receptor II (BMPRII)

- Activin Receptor-like Kinase 1 (ALK-1)

- Serotonin Receptors (5HT2B) and transporter (5HTT)

- All three of these mutations show incomplete penetrance and anticipation

- Must come together with environmental factors to cause disease

- All mutations seem to work on TGF-b pathway --> Increase levels

- Genetic predisposition, other environmental risk factors, and altered pathways and mediators all work together to cause disease

- Results in proliferation, thrombosis, and vasoconstriction

- Over time this leads to vascular remodeling and the pathological presentation of PAH

- Dyspnea on exertion

- Fatigue

- Lethargy

- Chest pain

- Exertional syncope --> Only pulmonary cause of this!!

- Cough, hemoptysis, and hoarsness (rare but possible)

- Abnormal second heart sound --> Louder than normal P2

- Right ventricular hypertrophy --> RV heave

- Right ventricular failure --> Seen on echo

- RVH and RVF are end stage for the disease

- Right Heart catheterization --> Gold standard for diagnosis

- Echocardiogram --> Can rule out left heart cause --> False positive rate of 30-40%!!!!

- PFTs

- CXR

- EKG

- Serology/HIV/LFTs

- V/Q scan or CTPA

- HRCT

- Influenced by numerous clinical parameteres

- Worse if <14 or >65 years

- NYHA Classes: I-II --> 58.6 months, III: 31.5 months, IV --> 6 months

- Aerobic activity as tolerated --> No anaerobic like soccer

- Minimize concomitant meds --> Might be causing PH

- Avoid pregnancy --> 30-40% mortality with pregnancy due to 1/3 increase in blood volume

- Avoid altitude

- Supplement oxygen

- Anticoagulation (coumadin)

- Diuretics

- Digoxin?

- Vasodilators

- Disease modifiers: Prostacyclin derivatives (epoprostenol), endothelin receptor antagonists (bosentan), exogenous NO, phosphodiesterase Type-5 inhibitors (sildenafil, tadalafil), and Ca channel blockers (Nifedipine)

- So hard to treat primarily because research is hard!! --> No animal models!! 

- Pneumonia

- Pulmonary edema

- Smoke inhalation

- Drowning/Near-drowning

- Pulmonary hemorrhage

- Pulmonary embolism

- Lack of central respiratory drive

- Drug overdose

- Progressive neuromuscular disease

- Intracranial injury

- Severe asthma or COPD exacerbation --> Extreme muscle fatigue

- Goals are to improve oxygenation and ventilation

- Watch the pH and PCO2 to follow --> pH most important!!

- Relieve respiratory distress

- Prevent or correct atelectasis

- Correct respiratory muscle fatigue

- Permit sedation and/or neuromuscular block (surgery)

- Reduce elevated intracranial pressure

- Correct severe acidosis

- Protect airway for future aspiration

1. Invasive: Endotracheal tube (ETT), tracheostomy (trach) tube, and nasopharyngeal tube

2. Non-invasive: Ambu bag/ Bag valve mask, face/nasal mask (CPAP), and body chamber (iron lung)

- Negative Pressure: Pt enclosed in structure/vest that creates negative pressure and forces diaphragms down to simulate normal breathing and expiration is passive

- Types of negative pressure: Iron lung, cuirass, and raincoat/poncho

- Positive pressure: Airway pressure is greater than atmospheric pressure --> Pushes air into the lungs

- Volume or pressure controlled settings

1. Volume: Vent delivers a set volume, flow rate is set and pressure varies --> Most common and answer for exam!!

- Types of volume control: Assist control (AC) and synchronized intermittent mandatory ventilation (SIMV)

2. Pressure: Vent delivers a set pressure, flow rate is set, and volume varies

- Delivers a minimum number of fixed volume breaths per minute

- Allows the patient to initiate extra assisted breaths

- Every breath is supported with a the fixed set volume whether it is vent or patient triggered

- Delivers a pre-set number of breaths at a fixed volume

- Allows patient to breath spontaneously over the vent

- Only the machine initiated breaths are supported/assisted by fixed volume

- Patient initiated breath is NOT assisted by vent

- Don't need to know this for the exam!!!

- Preset gas pressure is delivered to the airway for a specific length of time and at a guaranteed respiratory rate

- Tidal volume of each breath varies depending on the lung compliance and airway resistance

- Types: Pressure controlled ventilation (PC), Pressure regulated volume regulated (PRVC), and pressure support (PS)

- Least common vent settings and DONT need to know for exam!!

- Used in patients who are easy to oxygenate but have high inspiratory pressures --> Asthma and COPD

- Also used in combination with SIMV and when weaning patient off the vent

1. FiO2: Always begin at 100% --> Will try to wean down later

- Goal: PaO2> 60 mmHg with FiO2 40% or less

2. Tidal volume --> 6-8 cc/kg body weight

- Lower TV at higher RR better to prevent lung trauma

3. Respiratory rate --> Usually 10-12, faster for acidotic patient and lower for patient with vasospasm (asthma)

4. Mode of ventilation --> Always AC for us (volume controlled)

5. PEEP: Always begin with 5 cmH2O --> Increase by 2.5 cmH20 incriments to a max of 18-20 cmH20

- Look at ABG and PIP values --> Be especially careful about pH but don't let it consume you!! 

- Peak Inspiratory Pressure (PIP): Goal <35 cm H2O

- Plateau Pressure: Measured at the end of inspiration --> Goal <30 cm H2O

- If pressures are too high reduce TV

- May have to also raise FiO2 if decreased from 100% to improve oxygenation at lower TV