Quiz Yourself - Respiratory by AmnaKhan

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									Quiz Yourself Respiratory

• The FEV1 is reduced when:
– airway obstruction is present as with these diseases:
• Asthma • Emphysema

• FEV1/FVC ratio is reduced when
– airway obstruction is present. The normal ratio is:
• 70-75

• The FVC is reduced with
– restrictive lung disease
• Pulmonary fibrosis

Lung Volumes in Disease States

What does each of these represent?

What is the alveolar gas equation?
• PAO2 = FIO2 x (PB – PH2O) – PaCO2/RQ

What is the standard version (room air/temp)?
• PAO2 = 150 – PaCO2/RQ RQ = 0.8 – 1.0

What are the 2 ways to alter V/Q ratio?
Dead space
• Regions of the lung that are ventilated but not perfused – Anatomic?
• Normal. Like the trachea. About 30% of tidal volume.

– Physiologic?
• Includes anatomic, but in theory, when there are unperfused regions, as with a pulmonary embolism

• Regions of the lung that are perfused but not ventilated!
– V/Q mismatch = incomplete shunt. Responsive to O 2 therapy – Shunt is refractory to O2 therapy

Key pt: regions with a high V/Q ratio cannot compensate for regions with a low V/Q ratio b/c the high V/Q is normal!

What are the causes of hypoxemia and how do we distinguish them?
• • We distinguish between them using blood gas and A-a gradient Hypoventilation
– – indicated by hypoxemia with a high pCO2, normal A-a. Increasing frequency of breathing while lowering tidal volume increased the proportion of dead space ventilation to alveolar ventilation

• •

V/Q mismatch Shunt
– – indicated by hypoxemia with a HUGE A-a difference Common causes include intracardiac lesions, structural abnormalities of the pulmonary vasculature, filling of alveolar spaces w/ fluid or complete alveolar collapse


Low inspired O2 (Low altitude)

What is the diffusing capacity?
– Measured by DLCO – Impacted by diffusion barrier and aggregate surface area of alveoli – Measured with CO (but possible errors if the hemoglobin levels are low) – What does emphysema do?
• reduces the area  reduced DLCO

– What does fibrosis do?
• increases the thickness  reduced DLCO

What are the volume patterns for the following diseases?
• Obstructive diseases?
– larger TLCs
• Chronic bronchitis?
– increased RV, increased FRC

• Emphysema?
– increased RV, VERY increased TLC

• Restrictive diseases?
– smaller TLCs
• Fibrosis?

all lung volumes decreased
FRC reduced

• Obesity? • Inspiratory muscle weakness?
– – TLC reduced RV is elevated

• Expiratory muscle weakness?

Mechanisms of Hypoxemia
– – – – Hypoventilation V/Q Mismatch Shunt Low Inspired pO2

• How do we measure lung volumes?
• Helium dilution
– – – – Used to measure absolute FRC Doesn’t work if there’s lots of obstructed airways where a The small sealed box Makes measurements using Boyle’s law

• Plethysmography

What patterns of impairment are associated with:
• Obstructive lung disease?
• Restrictive lung disease?
– Diminished rates of expiratory flow (increased FEV1, decreased FEV1/FVC)
– Diminished lung volumes – Preserved expiratory flow

• What gives a characteristic scooped appearance in the expiratory phase of flow-volume loops?
– Airway obstruction like emphysema

• When is obstruction increased during inspiration?
– When it’s an extra-thoracic variable obstruction

• When is obstruction increased during expiration?
– When it’s an intra-thoracic variable obstruction

Normal Alveoli! What’s this?

Dilated bronchi

Muco-Purulent Debris in Dilated Bronc


• What is it?
– A chronic dilation of bronchi or bronchioles secondary to inflammation or obstruction

• Pre-disposing syndromes?
– Cystic fibrosis (CF) – Primary ciliary dyskinesia syndrome (Kartagener’s s.)

• Radiology?
– Airway dilation which extends to the periphery

• Pathology?
– Permanent dilation of bronchi – peri-bronchial inflammation and organization (fibrosis) – Can sometimes see mucopurulent debris in bronchioles


What disease is this?

Charcot-Leyden crystals – eosinophil granule contents

This is ASTHMA!!!!

Asthma Curschmann Spirals – mucus casts

• Clinical:
– – – – Airway hyperresponsiveness Triggers: antigens, exercise, drugs, infections, stress Acute, usually reversible diffuse bronchial narrowing Sxs: Wheezing, dyspnea

• Radiology:

– Alternating atelectasis and overexpansion – – – – – – – – Edema smooth muscle thickening BM thickening mucous cell hyperplasia increased submucosal eosinophils thickened intralumenal mucus Curschmann spirals – mucus casts Charcot-Leyden crystals – eosinophil granule contents

• Pathology:

Chronic Bronchitis
• A Clinical Diagnosis!
Increased numbers of mucinous glands in submucosa
– Definitional: Productive cough > 3months/year x > 2 years

• Radiology is non-specific • Pathology:
– Mucous cellular and glandular hyperplasia – May have submucosal chronic inflammation – May have respiratory bronchiolitis

• Might look like this:


Emphysema in COPD

• Clinical:
– Associated with cigarette smoking (component of COPD) – 1-antitrypsin deficiency, esp PIZZ mutation

• Radiology:
– Increased lucency (dark region)
• Upper>lower lobe suggests centrilobular type • Lower>upper lobe suggests panlobular type

– Possible increased AP diameter – Possible flattened diaphragm

• Pathology:
– Dilation of distal airspaces with septal destruction – Locations:
• Centrilobular: Cigarette smoke • Panlobular: A1AT deficiency or cigarette smoke

– Increased elastase activity

Bronchiolitis Obliterans/Organizing Pneumonia (BOOP)
• Clinical:
– Acute onset cough, dyspnea, fever, and malaise – Multiple associations, e.g. collagen-vascular dz – Most patients respond to corticosteroids

• Radiology:
– Multiple patchy airspace infiltrates

• Pathology:
– Patchy fibromyxoid plugs in distal bronchioles – the BO – Fibromyxoid plugs in alveoli, +/- endogenous lipid pneumonia – the OP – Think bronchiolar and alveolar airspace fibroblasts

Classification of Asthma
Intrinsic Asthma– No allergic or (personal family) history – Usually adult onset – Often follows severe respiratory illness – Symptoms usually perennial – More refractory to treatment, become other diseases, progress to vasculitis – Eosinophils still impt

Extrinsic Asthma– Strong family history of allergies – Usually onset at a young age – Other allergic manifestations in patients – History of specific allergic association triggers (e.g. pollen, animal dander) – Correlation with skin and inhalation responses to specific antigens – Type I hypersensitivity rxn – IgE mast cell and eosinophils

ALLERGIC SHINER: Edema/ What does this demonstrate? What is it? Discoloration Around the Eye

• What are the important cells in asthma?

• What’s the point of the methacholine challenge?

– Eosinophils (in sputum) – B lymphocytes in mediating the asthma – more impt

– It demonstrates that there’s something different in the architecture of the asthmatic’s airways that makes them non-specifically hyperreactive

• What is a key feature of the pathophysiology of asthma that contributes to death? • What are Creola bodies?
– Mucous plugs occluding airways

• What happens when you administer a beta-agonist? • What is AM dipping?
– You initially decrease the O2 saturation via V/Q mismatch.

– Agglomerated bronchial epithelial cells, seen in asthma

– When peak flow is decreased in the morning; associated w/ more severe asthma – Delayed reduction in FEV1 due to IgE and influx of inflammatory cells
– Corticosteroids (effective in reducing late phase reaction)

• What is the late phase reaction?

• What is the cornerstone of asthma therapy?

Findings/Diagnosing Asthma?
1. Spirometry
Increase lung volumes (TLC, FRC, RV) Decreased peak flow, FVC, FEV1, FEV1/FVC


Auto peak end expiratory pressure (auto-PEEP)-with rate respiratory rate. DLCO Methacholine challenge

Increased - useful in establishing dx

4. 5.


Reversible airflow obstruction when treated; albuterol

Increased in blood and found in sputum


Low PO2, low PCO2

Treatment of Asthma
• Avoid asthmatic triggers • Use bronchodilators
– Sympathomimetics – usually B2-AR specific to increase cAMP.
• albuterol • Salmeterol is a long acting B2

– Methylxanthines – inhibits PDE  increased cAMP – Anticholinergics – reserved for COPD

• Use anti-inflammatory drugs
– – – – Corticosteroids – the cornerstone of therapy Cromolyn and nedocromil – inhaled prophylactics Zileuton, Zafirlukast – decreases leukotrienes Omalizumab – anti IgE antibody

General Strategy for Management of Asthma
• Infrequent attacks?
– Inhaled sympathomimetics (B2)

• More frequent?
– Add an anti-inflammatory as maintenance, usually a corticosteroid

• Still not good enough?
– Regular use of inhaled B2 agonists – Add methylxanthines (theophylline)

• Significant attack?
– Systemic steroids

• Status asthmaticus?
– IV corticosteroids – Aggressive bronchodilators

Classification of asthma?
• • • • Mild intermittent Mild persistent – more than 2X/week, but <1QD Moderate persistent – daily symptoms Severe persistent – continual symptoms

• Common precipitating stimuli of asthma?
– Allergen exposure – involves histamines, leukotrienes
» Leukotrienes = why NSAIDS can precipitate asthma!

– Inhaled irritants – Respiratory tract infections – Exercise (cool air)

• When is airflow most compromised in asthmatics?
– Expiration

• Why is FRC chronically increased in asthma?
– Dynamic hyperinflation – can’t fully exhale all air – Persistent activity of inspiratory muscles

• What are the common symptoms of asthma?
– – – – Cough Dyspnea Wheezing – airflow through narrowed airways Chest tightness

• What is the mechanism of low PO2, low PCO2 in asthmatics?
– V/Q mismatch

• What are the 2 disorders under COPD? Basic defs?
– Chronic bronchitis – diagnosis based on chronic cough and sputum production – Emphysema – diagnosis based on destruction of lung parenchyma and enlargement of air spaces distal to the terminal bronchiole

• What’s the pathogenesis of alveolar destruction?
– Protease and protease inhibitors are in balance in lung – Smoking inhibits protease inhibitors – Neutrophils and macrophages in inflammation release damaging proteases

• What are the risk factors for COPD?
• Cigarette Smoking (also 2nd hand) • Hyperresponsive Airways • Occupational Factors (firemen) • Alpha1-antitrypsin Deficiency – PIZZ is BAD!
» Normally keeps elastase in check to maintain lung elastin

Mechanisms of Airflow limitation in COPD?
• • • • • loss of alveolar attachments obstruction of the airway due to inflammation airway-wall fibrosis airway smooth muscle constriction luminal obstruction with mucus.

• Loss of elastic recoil in emphysema results in:
– Decreased expiratory flow rates
• Lower driving pressure for expiratory airflow • Loss of radial traction from supporting alveolar walls

• Functional abnormalities in COPD?
– – – – – – Decreased FVC, FEV1, FEV1/FVC Increased RV, FRC, TLC Decreased DLCO in emphysema Increased Reid index in chronic bronchitis Hypoxia Hypercapnia in chronic bronchitis

• Major secondary problem with COPD? Causes?
– Pulmonary HTN  cor pulmonale (more common in chronic bronchitis patients)
• • • • Major Cause: Hypoxia  vasoconstriction Hypercapnia Polycythemia Destruction of the pulmonary vascular bed

• What is the protease-antiprotease hypothesis?
– – – – Alveolar integrity is maintained via a balancing act Smoke increases the # of PMNs in the lung PMNs produce elastase  degrades elastin Smoke oxidants, oxidants from inflammatory cells impair A1AT anti-elastase activity – Neutrophil elastase stimulate mucus release – PMNs and macrophages make matrix metalloproteinases  shift balance towards degradation

Clinical Distinctions Between Blue Bloater and Pink Puffer COPD Pathophysiology

Pink Puffer
Type A

Blue Bloater
Type B

Disease Association Major Sxs

Emphysema Dyspnea
Thin, wasted

Chronic Bronchitis Cough & sputum
Cyantoic, obese


Decreased Decreased

Decreased Normal

Normal or decreased Normal or increased

Elastic recoil

Hematocrit Cor pulmonale

Normal Infrequent

Increased Common

Treatment of COPD
• • • • • • • Bronchodilators Antibiotics Corticosteroids Supplemental O2 Exercise rehab Chest PT, postural drainage Surgery (last resort)
– Lung transplant – Lung volume reduction

• Vaccines: pneumovax, flu • Plasma A1AT if the patient is A1AT deficient • Mechanical ventialtion

Major Points from Smoking Cessation Lecture
• Tobacco dependence is chronic and requires repeated intervention
– If at first you don’t succeed, try, try again!

• ALL pts who smoke should be offered at least ONE tobacco dependence treatment.
– Pharmacotherapy CAN be helpful – Nicotine withdrawal can be fairly severe

• Clinicians, hospitals, etc must institute consistent ID, documentation, and tx of tobacco users • Brief tobacco dependence tx is VERY effective – all pts should be offered at least brief tx • Strong dose-response relation between tobacco dependence tx and it’s effectiveness

Major Points from Smoking Cessation Lecture
• The 3 types of counseling/behavioral therapy found to be very effective and should be used:
– Social Support within treatment – Social Support outside treatment – Skills training/problem solving

• Unless contraindicated, use of effective pharmacotherapies for smoking cessation in all pts trying to quit should be used • Tobacco dependence treatments are both clinically effective and cost-effective relative to other medical and disease prevention interventions • Setting a quit date is IMPT! • Set up follow-up dates after quit date to see your pt. • People tend to gain weight upon quitting…

5 first line pharmacotherapies for smoking abstinence that WORK
– – – – – Bupropion SR Nicotine gum Nicotine inhaler Nicotine nasal spray Nicotine patch

2 second line pharamcotherapies for smoking:
- clonidine - nortiptyline

• What is the most successful self-help format to quit smoking?
– Hotline “quitlines”

• Person-to-Person contact – how much helps?
– Even <3min is (moderately) better than none! – 10min or more is best

• Asking your pt to quit smoking helps/doesn’t help?
– It DOES!

• What are 3 things associated with unsuccessful attempts at quitting?
– Not practicing total abstinence – Drinking alcohol – Other smokers in da’ house

Peribronchovascular space Is dilated Giant cell

Sarcoidosis What disease?

• Clinical:
o o


Multi-system granulomatous disease Adults, B>W, F>M Dyspnea

• Radiology:


Interstitial infiltrates in bronchovascular distribution (= lympagenic distribution) Usually have hilar adenopathy (picked up on routine CXR) Tight, well-formed non-caseating granulomata Def of granulomata: Focal accumulations of epithelioid histiocytes

• Pathology:
o o

Hypersensitivity Pneumonia
Loose Granulomas

Interstitial expansion Peri-Bronchiolar Expansion

Hypersensitivity Pneumonitis (Extrinsic Allergic Alveolitis)
• Clinical:

Organic dusts


Doesn’t mean carbon based Means related to organic products

o o

Occupational or environmental exposure Acute and chronic: dyspnea, cough, fatigue Bilateral interstitial linear or nodular pattern Patchy peri-bronchiolar and interstitial chronic inflammation with loosely formed granulomata

• Radiology:

• Pathology:

Coal dust macules

Coal-worker’s Pneumoconiosis

Patchy Sub-Pleural Fibrosis

Ferruginous Body


Fibrotic Nodules

Late Silicosis

UIP: Sub-pleural fibrosis adjacent to normal lung


Usual Interstitial Pneumonia (UIP)
• Clinical:
o o

Syn. with “Idiopathic pulmonary fibrosis (IPF)” Adults, mean 51 yo; poor response to steroids, 66% mortality Patchy subpleural infiltrates, DDx asbestos, rheum Patchy interstitial inflammation; fibrosis alternating with normal parenchyma Temporally heterogeneous = ongoing injury to lung Morph overlap with rheum dzs, e.g. scleroderma

• Radiology:

• Pathology:

o o

Fibroblasts in the interstitium


Proliferative phase DAD

• Clinical:

Proliferative (Organizing) Phase Diffuse Alveolar Damage (DAD)

o o

> 1-2 wks after identifiable acute lung injury (ex: MVA, septic shock, kidney stone, inhalation of noxious chemical) Decreased pulm compliance -> mechanical ventilation 50% mortality
Diffuse, interstitial>alveolar pattern Interstitial + intra-alveolar fibroblastic proliferation Temporally uniform

• Radiology:

• Pathology:
o o

If it’s temporally heterogeneous = UIP


You HAVE to see interstitial fibroblastic proliferation

If it’s purely intra-alveolar = BOOP

What characterizes Pulmonary function in Restrictive Lung Disease?

Characterized by reduced FVC, normal or high FEV1/FVC ratio

Identify which is interstitial lung disease, obesity, Muscle and inspiratory & expiratory muscle weakness. Obesity Normal ILD Weakness





• What’s the differential diagnosis for bilateral diffuse infiltrates that mimic diffuse parenchymal disease?
o o


Congestive heart failure Pulmonary infection Lymphangitic carcinomatosis

• What are known causes of diffuse parenchymal lung disease?
o o

Inhaled organic dusts (asbestosis, silicosis, coal workers, berylliosis Inhaled organic antigens  hypersensitivity pneumonitis Iatrogenic (drugs – amniodirone, radiation)
IPF/UIP Sarcoidosis BOOP Goodpasture’s Wegener’s And many more… (Connective tissue disease associated, Chronic eosinophilic pneumonia, Lymphangioleiomyomatosis, Pulmonary Langerhan’s cell histiocytosis, Alveolar proteinosis, Pulmonary vasculitides)

• What are unknown etiological diffuse parenchymal lung diseases?

o o
o o o

Pathophysiology of Parenchymal Lung Diseases
• Decreased lung compliance (increased stiffness)
o o

Reduced FVC, reduced FEV1, normal ratio Reduced lung volumes TLC, FRC, RV Destruction of alveolar-capillary interface by inflammation and fibrosis, reducing the surface area for gas exchange (there is a reduced DLCO on testing) Hypoxemia Obliteration of small pulmonary vessels by fibrosis

• Diffusion impairment

• Pulmonary Hypertension
o o

Clinical Features of Parenchymal Lung Diseases
• Symptoms
o o

Dyspnea Cough (non-productive) Dry crackles or rales (sound like velcro) Clubbing Cor pulmonale
 

• Signs
o o o

JVD Loud P2, TR murmer edema

• What’s the major benefits of high resolution CT in diffuse parenchymal lung diseases?
o o

Detects sub-radiographic disease Distinguishes inflammation from fibrosis

Ground glass appearance suggests inflammation

• What is thought to be the pathogenesis of sarcoidosis?

A chronic systemic granulomatous idiopathic disease where there’s an immune response to an exogenous agent in a genetically predisposed individual Macrophages

• What key cells are thought to be involved in sarcoidosis?

Results in increased release of TNF


T cells (specifically CD4)
  

BAL will reveal CD4>CD8 There may be lymphopenia on peripheral blood smears MHC II is more impt than MHC I Results in increased IL-2, INF-gamma, and other cytokines

• What are the presentations/associated diseases of sarcoidosis?

 

  

Acute onset Bilateral hilar lymphadenopathy Eythema nodosum Fever Arthralgias Associated with a good prognosis


Eye manifestations

Acute or chronic uvetitis
 

Sjorgens – destruction of exocrine glands, specifically partoid and lacrimal Heerfordts – uvetis + uveoparotid fever, facial palsies, parotid swelling



Keratoconjunctivitis sicca – decreased tear production  conjuctival and corneal inflammation Papilledema Associated with chronic sarcoidosis Usually on face, sometime butt and extremities


Lupus pernio

• What are common abnormalities/diagnostic test results in sarcoidosis?


o o

o o


Hypergammaglobulinemia – T cells non-specifically activate Bcells  lots of Igs Hypercalcemia, hypercalciuria – increased Ca2+ absorption from GI tract due to increased vitamin D formation Lymphopenia – lymphocytes involved in granuloma formation CD4 > CD8 in BAL – CD4 plays a greater role in granuloma formation ACE elevated – due to vascular epithelial cells of granulomas CXR or HRCT – parenchymal infiltrates, hilar adenopathy, sublpleural micronodules, upper lobe predominant, honeycombing, ground glass appearance Gallium-67 scan – panda sign Diagnosis is one of exclusion and heavily reliant on biopsy

• How do we treat sarcoidosis?
o o

Systemic corticosteroids anti-TNF may be best tx (infliximab) hydroxychloroquine Stage I – adenopathy Stage II – parenchymal infiltrates & adenopathy Stage III – just parenchymal infiltrates Stave IV – fibrosis, hilar retractionm, cysts, bullae, honeycombing changes

• What is the staging of sarcoidosis?
o o o o

• Pathogenesis?


Inflammatory process of the walls  fibrosis due to dyregulated response to damage of alveolar epithelial cells Factors that are dysregulated  fibrosis?
    

Cytokines Chemokines Matrix metallic proteases and balance with inhibitors Decreased fibrinolysis Eicosanoid imbalance: increased luekotrienes, decreased prostaglandins

• Commonly presents in?

Older adults, M>F Exertional dyspnea that increases over time Non-productive cough Possible clubbing

• Signs and Symptoms?

o o

• What are common abnormalities/diagnostic test results in UIP?
o o o o

Velcro-like dry crackles Peripheral edema or cor pulmonale in advanced stages Hypoxemia, cyanosis, clubbing CXR
  

Honeycombing Diffuse reticulations NO hilar enlargement Patchy, peripheral subpleural densities associated with small cystic spaces



• Pathology of UIP?
o o o

Honeycombing Fibrosis Temporal heterogeneity

What Occupational Exposure Materials can cause inflammatory reactions in the Airways?

Secretory Inflammation
   

Formaldehyde – upper airways Ammonia – upper airways Particulates (coal, dust, cotton) – bronchitis Nitrogen dioxide – bronchiolitis Ozone, cotton dust – non-specific reactivity TDI – occupational asthma


Hyperreactive Airways
 

What Occupational Exposure Materials can cause Parenchymal responses Acutely? Chronically? o Acutely


Pulmonary Edema due to toxic reactions  Chlorine, phosgene  Acute silicosis Hypersensitivty Pneumonia  Organic materials – farmer’s lung (mold spores in hay)  Inorganic materials
Nodular fibrosis  Coal – macules  Silica – collagenous lamellated nodules  Beryllium – Granulomata Diffuse Fibrosis  Asbestosis Cancer  Asbestos  Chloromethyl Ether, Coke oven emissions





• What are the causes/common types of pneumonoconiosis?

Nodular or diffuse fibrosis…
   

Silicosis Asbestosis Berylliosis Coal Worker’s

• Important things to do to make a diagnosis in occupational exposure related respiratory diseases?
o o o o o o o

Take a detailed history CXR to document pneumonoconoiosis Blood studies to document specific exposures Lung tissue analysis Measure peak flow throughout week Specific inhalational challenges Investigation of workplace by industrial hygienist

Respiratory Diseases due to Asbestos

Non-Malignant A. Pleural Disease
1. Pleural Effusion 2. Diffuse Pleural Thickening 3. Localized Pleural Thickening (Plaques)


B. Diffuse Pulmonary Fibrosis (asbestosis) Malignant A. Malignant Mesothelioma
- bad stuff - cigarette smoking is NOT related - latency is 30-40 years

B. Bronchogenic Carcinoma C. Possibly Laryngeal Carcinoma

Asbestosis – a restrictive Lung Dz
• Latency period?

20-30days Ferruginous bodies! Peri-bronchiolar inflammation and fibrosis May eventually honeycomb Tendency towards the lower lobes of the lungs

• Pathologic features?
o o o


• Clinical Symptoms and CXR?
o o o o

Dyspnea on exertion Dry cough Late inspiratory crackles in bases Opacification in bases Pleural thickening

Occupational Asthma
• Definition?

Clinically significant variable airflow obstruction due to specific workplace agent in lower [ ]s than should cause non-specific irritant response in normals or asthmatics who are not sensitized
  

• Risk factors?
Potency of sensitizing material Level of exposure Accidental high exposures Individual patient – atopy and smoking

• Types of presentations:


o o

Typical immediate onset – w/in 30 minutes; clears hrs after leaving work. AM cough & sputum. Responds to bronchodilators Typical late onset – may not have wheezing; 4-8hrs afterwards with longer duration. Refractory to bronchodilators Dual Response Recurrent Attacks Post Exposure – at night after exposure Inhaled steroids and bronchodilators

• Standard Treatment:

Reactive Airways Dysfunction Syndrome (RADS)
• Characteristics:
o o o




No preceding respiratory symptoms. Onset of symptoms after single high level exposure to an irritant. Onset of symptoms is abrupt (without 24 hours) and symptoms persist for at least 3 months. Symptoms of variable airway obstruction and/or hyperresponsiveness. Non-specific airway hyperresponsiveness present (methacholine challenge). Persistent airway inflammation but lack of eosinophils

Pleural Diseases
• What is pleuritic pain?

Caused by inflammatory processes that intensify upon breathing Air escapes into pleural space  positive pressure Air can’t escape on exhalation By compromise of venous return Trauma  sucking wound Iatrogenic - Overzealous use of positive pressure ventilation, central lines, lung biopsies Abnormal lungs  air trapping (think asthma) Spontaneous in very tall people

• What’s going on with a tension pneumothorax?
o o

• How can a tension pneumothorax cause shock?

• How can ANY pneumothorax be caused?


o o

• What kind of pneumothorax?
o o o


21 y o center for BB team Has sudden onset of R sided chest pain & mild dyspnea Patient is uncomfortable but vital signs are WNL Not Sean May hopefully!
 

Pneumothorax disease b/c it’s a popped lung, the pneumothorax is limited and should spontaneously resolve

o o


20 y o severe asthmatic Intubated & on mechanical ventilation Suddenly becomes hypotensive & cyanotic

This is a tension pneumothorax – must decompress the patient emergently!

• What will the CXR look like on a pneumothorax?

On side of pneumothorax


Absent vascular markings Appearance of a little nub near hilum (atelectic lung) Diaphragm depressed downwards Mediastinum, trachea, other structures shifted over


On side opposite of pneumothorax


It’s a dark and stormy night… And a patient is brought into your ER with:
   

Pleuritic chest pain Dyspnea Dullness of lungs to percussion Egophony at upper level Pleural friction rub



After you’re told he’s NOT possessed and isn’t just freaked out after watching that scary movie, you get a CXR. That CXR shows:
  

Blunting of the right costaphrenic angle Elevation or flattening of right hemi diaphragm And the mediastinum shifted to the left side


Then the scary, menacing attending asks you what does he have. You, being the superstar that you are, reply:

“Why A Pleural Effusion, DUH!”
• How is normal pleural fluid made?

Generated by Starling forces across a capillary bed
Blunting of costophrenic angle on upright film Elevation or flattening of hemi diaphragm on upright film Diffuse haziness of hemi thorax on supine film If large, will cause shift of mediastinum to contra-lateral side Thoracentesis

• Radiographic signs of pleural effusion include:
o o o o

• How do you relieve a massive pleural effusion?

 

Helpful diagnostically Helps relieve symptoms Remove 1500cc or less!
 

Otherwise, you might suddenly inflate the lung. Too little surfactant  pulmonary edema

How do you relieve a massive pleural effusion?

• Thoracentesis
o o o

Helpful diagnostically Helps relieve symptoms Remove 1500cc or less!

Otherwise, you might suddenly inflate the lung. Too little surfactant  pulmonary edema

• How do you safely do a thoracentesis?

Make sure the fluid is freely flowing and not loculated

Use a lateral decubitus film

o o

Use ultrasound to locate effusion Be sure to draw close to the upper part of the rib directly below the needle you’re using, or you might hit an intercostal artery, vein, nerve

What are Lyte’s Criteria? Why do we use them in the first place?
• Helps us distinguish between an exudate and a transudate pleural effusion
o o

o o

Ratio of pleural-fluid protein to serum protein > 0.5 Ratio of pleural-fluid LDH > 0.6 Pleural fluid LDH level > 2/3 upper limits of normal for serum Any one of these characteristics means the fluid is an exudate

• What other studies might you do on fluid from a pleural effusion

cell count & differential, glucose, cytology, Gram stain, AFB stain & culture, amylase, cholesterol, triglyceride level, pH, adenosine deaminase

• What if the effusion is borderline according to Lyte?
Look at albumin gradient - If difference btw albumin in serum minus pleural fluid is > 1.2 than more likely a true transudate

What are the potential causes of a Transudate?

o o

o o

CHF – due to increased pulmonary venous pressures, usually bilateral, usually resolves in 48 hours after diuresis Nephrosis – low oncotic pressures Cirrhosis Atelectasis – increased negative pleural pressure Ascites – can preferentially form in pleural space, hepatichydrothorax
 
  

• What are the potential causes of a massive exudate?
Malignancy Trauma - hemothorax Empyema – bacterial infections Chylothorax – disruption of thoracic duct Rarely, TB


Causes of bloody exudates?
  

 

Cancer Pulmonary infarction Penetrating & nonpenetrating trauma Central line malplacement Chondrosarcoma S/P CABG
Chylothorax Empyema


Causes of turbid exudates?
 

• How do you define a hemothorax?
o o


Defined as pleural fluid hematocrit of 50% of blood hematocrit Will coagulate & may lead to loculation with complications of fibrothorax & possible empyema If small, may defibrinate & remain free flowing

So the good doctor said there’s a good exam question in here… What kind of cell count in an exudate would make you suspect cancer or Tb?


>50% lymphocytes!


Now what additional information on this exudate could help you decide that it’s probably NOT Tb?

>5% mesothelial cells

Remember, mesothelial cells are normally found in pleural fluid to some degree since they are the cells that comprise the pleura!

• Why should you distinguish between an empyema and a parapneumonic effusion?

b/c empyemas need to be drained STAT!

• What the hell IS a parapneumonic effusion?
Effusion secondary to a pneumonia Resolves with antibiotics. Course is usually very benign
Implies active bacterial infection in the pleural space. Failure to recognize & drain can lead to unresolved sepsis & fibro thorax

• Great, so what about an empyema and why do I care?
 

• So how do I tell the difference between the two?

Well if it’s an empyema, there should be:
  

Gross pus pH < 7.1 glucose < 40 positive Gram stain or cultures


And if it’s all borderline you need to retap that…um…lung…

Ack! It’s an Empyema! What Do I do?
o o o

Well a tube thoracostomy for one Antibiotics to get those microbes Thrombolytics if loculated or stops draining despite fluid present on X-ray
Helps combat if the thing is trying to wall itself off  Don’t let it hide – go and get it!


Decortication if unable to achieve drainage & lung is trapped in fibrinous peel

Yeah – RIP off that clot and scar tissue that I wish you saw…


So what if I don’t and say I did?


Untreated you might get empyema necessitans (where it attempts to drain through the chest wall b/c you were too lazy to drain it) Or you might get a bronchopleural fistula causing overwhelming sepsis

Cartilage in excess and disarray
Solitary Pulmonary Nodule

STOP! Hamartoma!

o o

It’s BENIGN!!!! Clin:


Adolescence  adulthood None in newborns - not congenital



Solitary nodule +/- popcorn calcification Peripheral > central Gross: solitary, lobulated, cartilagenous Micro: normal tissues in excess/disarray  If it’s calcified, it’s comforting b/c it tends to be nonmalignant!


 

What are the Malignant epithelial neoplasms (Carcinomas)?
o o o o

Squamous cell carcinoma Adenocarcinoma Large cell undifferentiated carcinoma Small cell undifferentiated carcinoma
One of these things is not like the others. One of these things just doesn’t belong…

Small cell is treated differently and has a much more severe progression!



Squamous Cell Carcinoma

Squamous cell carcinoma
• Clin:

Smokers association?

YES 20-30% of common carcinomas




May secrete PTH-like compound

• Radiology:

central > > peripheral Bronchi > Larynx > Trachea KEY CHARACTERISTICS? +/- Desmosomes (intercellular bridges) +/- Keratin production, e.g. keratin pearls

• Path:


Primary Gland formation

Pleural effusion Mucin production (red on PASd stain)

• Clin:
o o

30-40% of common carcinomas Smoking association?

Most common carcinoma in non-smokers, but 80% of adenoCAs occur in smokers

• Rad:

peripheral > central

• Path: o +/- glands o +/- mucin

Bronchiolo-alveolar carcinoma subset

Bronchiolo-alveolar carcinoma
- Note the mucin in the alveoli. Gas exchange is gonna suck in this patient!

Bronchioloalveolar carcinoma (BAC)
• Subset of?

Adenocarcinoma Rising incidence (presently 20-25%) Associated w/ smoking?

• Incidence?
o o

Not associated with cigarette smoking

• Rad:

Peripheral, can be multifocal and bilateral Lepidic (butterfly-like) growth pattern Mucinous or non-mucinous Unifocal or multifocal

• Path:
o o o

Large cell undifferentiated carcinoma

Large cell undifferentiated carcinoma



Clin:  10% of common carcinomas Rad:  non-specific Path:  H&E: Undifferentiated  cDNA microarrays: distinct disease
 Basically,

it’s a carcinoma with no distinguishing features

Necrotic carcinoma

Viable carcinoma Normal lymphocytes At diagnosis Response to therapy

Small Cell Carcinoma

Small cell carcinoma
• Clin:



o o

20 % of common carcinomas Paraneoplastic Syndromes:

Ectopic ACTH, ADH, Eaton-Lambert, carcinoid s.

o o

Commonly high stage at presentation Responsive to chemo/RT, but low 5 yr survival Central in >90% Frequent metastases to LNs and distant sites
Malignant cytology; high N:C ratio No nucleoli; punctate salt and pepper nucleoli High mitotic activity and tumor cell necrosis

• Rad:
o o

• Path:
o o



Think small round blue cells!

Thin delicate microvilli

Associated w/ ferruginous bodies

Visible C-P Angle

Loss of C-P Angle thickness pleura Normal Thickened pleura = Pleural effusion or mass


Most Common Metastatic carcinomas in the Lung?

Breast adenoCA  GI adenoCA  Renal adenoCA  Head/neck squamous cell CA

Lung Cancer - Basics
• What are the 2 most impt risk factors for lung cancer?


Genetics Smoking (15% smokers will get lung cancer; 85% CA in smokers)

• What types of molecules are the predominant carcinogens in cigarettes?

Polycyclic hydrocarbons
WOMEN Differences in metabolism, CYP450 Hormonal effects in lungs 3p – NSCLC Ras – adenocarcinoma Myc – small cell NSCLC – p53 Rb – small cell Random breaks in 1, 3, 5, 7, 15, 17

• What sex is more susceptible to lung CA? Theories why?
o o


• What are some mutations that have been implicated?

o o

o o

More Lung Cancer Basics
• Most common sites of metastases:
o o o


Liver Bone Brain Adrenals

• What are the paraneoplastic syndromes associated w/ NSCLC?

Clubbing, Hypertrophic orthropathy (adeno), Hypercalcemia (squamous)

• What are the paraneoplastic syndromes associated w/ SCLC?

SIADH (hyponatremia), Cushings, Lambert-Eatons, peripheral neuropathy, cerebellar degeneration

Diagnostic Tools for Lung CA
• The Basics
o o o o

Detailed hx and physical (esp lungs and supraclavicular nodes) CXR Chest CT Lab tests: CBC, liver fxn, alkaline phosphatase, serum Ca 2+ For central, endobronchial lesions

• The Good, Special Stuff

Sputum cytology (3+ specimens for 90% yield) Bronchoscopy

Can also do transtracheal needle aspirate of nodes near trachea and bronchi


For peripheral lesions

Transthoracic needle biopsy (CT guided) Thoracentesis (effusions)

Malignant (w/ CA cells in exudate) or paramalignant

Staging Lung CA

What’s Useful?
Limited stage disease vs. extensive stage disease  Limited stage - confined to hemithorax; within a radiation port  Extensive - Tumor beyond a radiation port, includes malignant pleural effusion; what most pts present with


What’s not so useful?

TNM system (which is used in NSCLC)
 


T – location, size N – nodes M – metastases


Stage I – no nodes involved EARLY Stage II – nodes on the same side/hilum of CA Stage III – nodes/mediastinum Stage IV – another organ involved or a second lesion in the lung

IIIA, IIIB = locally advanced IIIB, IV = advanced, effusion

• Tricks to help us stage NSCLC?

 


Chest CT FDG PET Scan Mediastinoscopy Bone scan CT/MRI of brain Abdominal CT (liver, adrenals) Biopsies of extrathoracic lesions


 


• Treating NSCLC
o o


Early – surgical resection + chemo Locally Advanced – chemo + surgery or radiation Advanced – chemo

Can help improve sxs, cost effective, increases 1yr survival

• Treating SCLC
o o

Limited – chemo + radio Extensive – chemo, w/ palliative radio as needed

 Adenocarcinoma
     

Most common NSCLC in US Smokers and non-smokers Peripheral (in the lung parenchyma) May arise in area of previous scarring More likely to spread to lymph nodes and outside of the chest Hypotrophic orthopathy or clubbing alone may be present Subtype of adenocarcinoma More common in women More common in non-smokers than smokers for poorly defined reasons Cough and bronchorrhea (frothy sputum production) Variable radiographic presentation: solitary nodule, multiple nodules, infiltrate/consolidation with air-bronchograms

 Bronchioloalveolar carcinoma
  

 

 Squamous cell carcinoma
  

 

Exclusively in smokers Generally arise in proximal airways May cause obstruction of the airway with distal atelectasis, post obstructive pneumonia May cavitate Hypercalcemia due to PTH like substance (weakness, dehydration, mental status changes), clubbing 15-20% of all lung CAs (decreasing) The least common lung CA Exclusively in smokers Generally originate within bronchial wall Bulky central tumor with extensive mediastinal lymph node involvement Rapid grown and early distant metastases Paraneoplastic syndromes especially SIADH (low sodium or hyponatremia associated with mental status changes)

 Small Cell Lung Cancer
 
   


Got Your Sound On?

Time to Take a Study Break!!!
Is it close to midnight?

And that exam is lurking in the morn

Types of inflammatory responses/cells in infections and likely disease process
 Neutrophils  Acute pneumonia (usually bacterial)  Usually in alveoli  Lymphocytes  Usually viral or atypical pneumonia  Usually in interstitium  Granulomatous inflammation (epitheloid histiocytes, lymphocytes, giant cells)  Usually mycobacterial or fungal pneumonia

Neutrophils filling alveolar space in acute pneumonia

Interstitial lymphocytes in viral pneumonia

Giant Celll

Histiocytes and multinucleated giant cells (granulomatous inflammation) in mycobacterial pneumonia

Common bacterial pneumonia microbes
• Community acquired
 normal flora, common agents  Pneumococcal (streptococcus pneumoniae)  Klebsiella  Hemophilus, Staph aureus, other strep

• Nosocomial (hospital acquired)
 Pseudomonas aeruginosa

especially in cystic fibrosis patients

 Methicillin resistant staphylococcus aureus (MRSA)

• Types of pneumonia patterns on CXR
 Lobar (entire lobe  Bronchopneumonia (patchy in more than one lobe surrounding a bronchus

What is the agent of Pneumococcal pneumonia? How do you get it? Sxs? Pathology?
• Streptococcus pneumoniae is the prototype of bacterial pneumonia  Encapsulated gram + cocci (diplococcus)  Normal resident of the nasopharynx  Often preceded by a viral infection  sets you up for bacterial pneumonia  Clinical: fever, chills, chest pain, purulent or bloody sputum, opacified chest X ray  Pathology


Early: pulmonary edema and proliferation of bacteria, intraalveolar accumulation of neutrophils and erythrocytes (―red hepatization‖) Later: serum and fibrinous exudates, intra-alveolar organization, macrophages (―gray hepatization‖)

What are the sxs of Legionella pneumonia?
• ―Legionnaires’ disease‖  Acute onset of malaise, fever, pneumonia, myalgias, abdominal pain, diarrhea

• Type of bact? Gram stain? How do you see it?
 Small gram negative bacillus  Need special stains to visualize

• What does CXR look like?
 Pathology: bronchopneumonia with multiple lobes involved, alveoli filled with fibrin and inflammation  X ray is frequently more worrisome than clinical symptoms would suggest

What patients are susceptible to pneumonias caused by anaerobic bacteria?
 Anesthetized patients  Alcoholics  Seizure disorder

• What are characteristics of anaerobic pneumonias?
 Normal inhabitants of oral cavity  Streptococci, fusobacteria, bacteroides  Often cause necrosis  Foul smelling sputum  May develop abscess formation

What are common complications of bacterial pneumonias?
• Lung abscesses
 Walled off area of infection with destruction of pulmonary parenchyma  destruction of all normal architecture  Clinical: fever, cough, foul smelling sputum, mortality 5-10%

• Pyothorax/empyema
 Infection of pleural fluid with purulent material within the pleural space.  May become loculated (fibrous walls around the inflammation), which requires drainage as well as antibiotics to treat.

A clinical problem b/c it doesn’t have normal blood flow for tx with antibiotics AND it doesn’t drain normally w/ a chest tube

• Bacteremia
 Bacteria within the bloodstream  May seed distant sites  Endocarditis, meningitis, pericarditis

What does this demonstrate?

Center of pulmonary abscess showing acute inflammation with destruction of Normal pulmonary architecture (no alveolar walls)

Alcoholics on the right lung b/c that’s where aspiration goes!

An abscess.
Who’s likely to get it and where?

necrotizing granulomatous inflammation

Peripheral focus of granulo Inflammation (Ghon focus)

Granulomatous inflammation In hilar lymph node

Beaded look to the bact
Positive AFB

Initial tuberculous infection: Ghon complex (Ghon focus + involved hilar nodes)

• Primary tuberculosis
 Inhalation of aerosolized droplets  settle in periphery of lower lobes  Ghon complex: Peripheral focus of infection (granuloma, Ghon focus, often in a lower lobe) and the infected hilar/ mediastinal lymph node  Pathology: caseous (cheese like) necrotizing granulomatous inflammation  90% of primary infections are asymptomatic; 10% progressive primary Tb (enlarged lesion >6cm, spread to other parts of the lung, children or immunosuppressed patients)

• Secondary tuberculosis
 Reactivation of primary Tb OR a new infection in previously sensitized pt  Clinical: fever, fatigue, weight loss, sweats, cough, hemoptysis  Numerous caseating granulomas most common in the apical and posterior segments of upper lobes (highest aeration)  These may heal and calcify, but some may erode into a bronchus, leading to tuberculosis cavity  Usually 3-10 cm, often in apex of lung  Communication with bronchus allows dissemination of organisms throughout lung

Complications of tuberculosis
• Miliary Tb  Multiple small (millet seed size) granulomas in many organs  Results from hematogenous dissemination  Kidneys, adrenals, bone marrow, spleen, liver lymph nodes are common sites • Hemoptysis  Erosion of inflammatory response/Tb granuloma into a pulmonary artery • Bronchopleural fistula  Erosion of inflammatory response/granuloma into the pleural space, resulting in Tb empyema • Unusual complications – you cough up Tb and swallow it, and it’s happy to colonize somewhere else

Tuberculous laryngitis Intestinal tuberculosis

Other mycobacterial diseases
• Mycobacterium avium-intracellulare
 Found in soil, water, food  Causes disease in immunocompromised patients, particularly HIV+ (HIV Tb)

• Mycobacterium kansasii
 Associated with Hairy cell leukemia

• Mycobacterium bovis
 Infection from ingested milk (the bow Tb)

• Found in:
 in infected dust, bird droppings

• Appearance:
 dimorphic fungus with tiny yeast forms

• Common location:
 Endemic in midwest and southeast US, particularly Mississippi and Ohio valleys

• Clinical and pathologic findings
 Similar to Tb  Yeast phagocytosed by macrophages and PMNs

 result in focal infections with parenchyma and hilar lymph nodes  granulomas and caseating necrosis  Old granulomas frequently calcify
 Immunosuppressed patients may have disseminated disease involving lungs, liver, adrenals, intestines

• Appearance:
 dimorphic fungi with large thick walled sporangia 30-60 microns filled with endospores 1-5 microns

• Geography/location:
 Endemic in southwestern US, particularly San Joaquin valley.

• Clinical and pathologic findings
 Similar to Tb and histoplasmosis,  Immunocompromised patients may have release of endospores into lung causing with fulminant disease with purulent response  Meningeal and MSK involvement possible

• Appearance?  yeast 4-9 microns with mucinous capsule • Found in?  pigeon droppings • Clinical and pathological presentation?  Clinical disease almost exclusively in immunocompromised patients  Lung is the portal of entry  CNS is the most common symptomatic site (especially cryptococcal meningitis)  Organism may be demonstrated in CSF, lung washings/BAL and biopsy with special stains (India Ink, mucin stains). Cryptococcus is one of the few fungi with mucicarmine positive capsule.

Cryptococcus: mucicarmine positive capsule Cryptococcus on GMS stain showing narrow based budding

• Appearance:
 a large dimorphic fungus with broad based budding.

• Geography/location:
 In US in Mississipi and Ohio River valleys and Great Lakes regions

• Pathology:
 Disease usually confined to lungs, causes mixed granulomatous and suppurative inflammation

Blastomycosis: Large yeast with broad based budding

• Appearance:  septate hyphae with acute angle branching, found in soil and decaying plant material • Diseases/Presentation  Aspergilloma (Mycetoma, ―fungus ball‖)


Grows with preexisting cavity, often Tb cavity Tangled mat of hyphae within cavity, X-ray may show mass and air within cavity Asthmatics develop immunological reaction to Aspergillus, w/ infiltrates on CXR, eosinophilia of blood/sputum, wheezing, cough and sputum production Treatment with steroids to control immune response It’s not the fungus that hurts you, it’s your body’s response

 Allergic-Bronchopulmonary aspergillosis (ABPA)

 

Aspergilloma showing non-invasive fungus within granulation tissue line Aspergilloma (fungus ball) within pre-existing cavity cavity

Aspergillus: septate hyphae with 45 degree branching

Aspergillus within blood vessel wall

Invasive aspergillus

Mucormycosis (Zygomycosis)
• Caused by inhalation of spores of several fungi (Mucor, Rhizopus, Absidia) ubiquitous in soil, food, decaying vegetable material • Appearance?
 grow as non-septate hyphae

• Common patients?
 patients with underlying illness, particularly diabetics

• Common presentation?
 rhinocerebral (nasal sinuses and brain) and pulmonary. Causes vascular invasion, septic infaction, hemorrhage


Pneumocystis carinii • What is it?
 A common pulmonary pathogen causing pneumonia in immunosuppressed patients, especially HIV

• What do you see?
 Trophozoites and cysts, latter identifiable with GMS stain, fills alveolar spaces with organisms and proteinaceous fluid, preventing gas exchange

• Bronchoalveolar lavage useful for diagnosis • Causes dyspnea and CXR with infiltrates • Dx by cytology

Pneumocystis on GMS stain: cup shaped organisms within alveolar spaces

Viral pneumonias
• Cytomegalovirus – most common viral infxn  Interstitial pneumonia in infants and immunocompromised patients, especially organ transplant patients, now we screen (donor & recipient)  Large cell, big nucleus w/ large, single basophilic intranuclear inclusion • Measles  Multinucleated giant cells with nuclear inclusions

• Varicella (chicken pox and herpes zoster) are usually asymptomatic  Interstitial mononuclear cell pneumonia, may produce focal necrosis  Nuclear eosinophilic viral inclusions, may be mutlinucleated • Herpes simplex
 necrotizing tracheobronchitis and diffuse alveolar damage • Other viruses (especially in children)  Adenovirus  Respiratory syncytial virus

Measles pneumonia: multinucleated giant cells with viral inclusions

Cytomegalovirus pneumonia

Viral inclusion
Herpes virus on cytology specimen

Mycoplasm pneumonia: sparse lymphocytic interstitial inflammation

• Small free-living prokaryote, common cause of acute selflimited pneumonia and tracheobronchitis, • milder than usual bacterial pneumonia (―walking pneumonia‖) • Highly transmissible through airborne droplets • Cause of 15-20% of pneumonias in developed countries • Pathology: patchy consolidation, mononuclear infiltrate, usually of a lower lobe • Very common but not very bad • You’ll see something on CXR but not lots of sxs  Really common at college/in dorms

What are common host defenses to respiratory infection?
   

Upper Airway (nose) Epiglottis/Larynx Epithelial Tight Junctions
Mucociliary and Cough Clearance

 

“Innate” (lysozyme; lactoferrin; “defensins”) Immune Response
 

Secretory IgA (nasal/bronchial) Humoral Antibody Cellular

 

Alveolar Macrophages (AM) Inflammatory Response (PMNs, etc.)

• What defenses are protecting the proximal airways and nose?
 Primary Components: cilia, liquid/mucus, submucosal gland secretions  Mucociliary clearance – respond to neurohormonal and mechanical stimuli  Secretions of the submucosal glands – what’s in this?

Lysozymes  IgA – neutralizing; secreted as a dimer  IgG – opsonizing • What are the defenses in the alveoli/distal airways?

 No cilia or mucus  Macrophages – they can seek and phagocytose pathogens, as well as coordinated the cellular response via chemotactic factors and cytokines  IgG

• Secondary defense mechanisms thoughout the lung?
 Neutrophils and other inflammatory cells

Lung Defense Failures
• Common:
 viral infection - after influenza, other infxns can occur  cigarette smoking  COPD  patients w/ underlying lung disease

• Severe failures of lung defense include:
 AIDS  Medications (corticosteroids like prednisone, other immunosuppressives, chemotherapy  Malignancies (leukemia, lymphoma) – can lower cell and antibody mediated immunity  Endotracheal tubes – HAP

Routes of Infection of Lung
• Aspiration
 Microaspiration of pathogens colonizing the oropharynx (your upper away)  Gross aspiration of mouth/GI tract contents into lungs

• Inhalation
 Ambient droplets/particles entrained (e.g. TB, fungi)

• Hematogenous
 e.g. Staph. aureus with IVDA, endocarditis, or a catherter

Typical vs Atypical Pneumonia
Typical Pneumonia • Rapid onset • Ill appearing • High fever, rigors (shaking chills), chest pain, purulent sputum • Consolidation, rales on exam • Leukocytosis (15-20K)
• Airspace filling/lobar infiltrate on CXR with air bronchograms • Meant to describe: S. pneumo, S. aureus, GN bacilli like Klebsiella Atypical Pneumonia • Indolent onset (7-10days) • Less ill appearing • Low-grade fever, malaise, headache, dry cough • Rales without consolidation • Mild/no leukocytosis; negative cultures

• Patchy/interstitial infiltrates on CXR • Meant to describe: Mycoplasma, or Chlamydia


This is the most important test that needs to be done in diagnosing pneumonia?
• Chest Radiography
 May distinguish pneumonia from other problems (bronchitis, CHF, TB, PE, cancer)  Assesses severity/distribution (multilobar) of disease and identifies complications (pleural effusion, abscess, empyema)  Many patterns observed
 

Airspace filling processes (lobar; patchy ―bronchopneumonia‖) Interstitial patterns Location, cavitation, adenopathy…

CXR will ESTABLIGH THAT YOU HAVE PNEUMONIA… But CXR won’t tell you what the responsible pathogen is

• YES

Since CXR and clinical presentation only tells you the patient has pneumonia, do you even care what the causative microbe is?

 The pathogen determines how you treat it (and in my case, how much I freak out)

• Great, so how do I figure out WHAT the pathogen is then?
 Sputum Gram’s stain and culture: used but utility debated due to high false+ and false- rates  Blood cultures: for hospitalized patients (specific, but not sensitive); much better.

Strep pneumoniae causes the most + blood cultures

 Ancillary testing for specific organisms
 
 

Legionella: Urinary antigen immunoassay (serotype 1) DFA, selective media Chlamydia, Mycoplasma: serologies, but these are relatively unhelpful in the acute setting TB: AFB smear/culture Fungus: KOH/culture

So when is this sputum Gram stain & Culture going to be worth me missing sleep?
• When you’ve got…
 Large numbers of bacteria with a single morphology observed in setting of many PMN’s and few/no squamous epithelial cells (i.e. lower airway specimen)  Obtained before antibiotics  Detection of a non-colonizer (mycobacteria, endemic fungi, Legionella, PCP)  That’s when I go:

(yes I know I’m a dork, but you’re laughing – admit it. And I have to entertain myself SOMEHOW!)

This is a sputum sample and it tells us?

That it was probably an incompetent med student who this specimen, b/c it SUCKS. Look at all the squamous epithelial cells and where are the inflammatory cells?!?!?

So after you fix that previous person’s mistake, you see this. What are you thinking?

Besides thinking “damn, I’m good you should be thinking STREP!!!

When Do I give up on the whole idea of a bacterial pneumonia and consider TB/fungal agents? • CXR:
 Upper lobe cavitary infiltrate: TB!!

• Clinical course:
 Indolent course x weeks/months  Non-resolving on treatment

• Exposure history:
 Outdoorsman (Blastomycosis)  Desert southwest (Coccidioidomycosis)  TB contacts or from endemic area

The patient asks you to predict how bad the infxn is. You’ll assess the severity looking at what? And what’ll make you panic?
 Age >60 years,  comorbidities (cancer, ―organ failures‖, immunosuppressed conditions, CHF)

• Clinical findings:
 altered mental status  severe vital sign abnormalities

(RR>30; SBP < 90; T>40 or <35; HR >125) • Lab data:

 WBC >30k or <4k;  hypoxemia;  acidosis

• CXR:
 multilobar involvement,  fulminant progression

or you could just use a magic eight ball…

Pathogens ~ Modifying Risk Factors
• Aerobic GN bacilli
like Klebsiella

Alcoholism, nursing home, cariopulmonary disease Loss of consciousness (alcohol, seizure), swallowing dysfunction, poor dental hygiene, airway obstruction COPD, smoker Nursing home, post-influenza, IVDA, bronchiectasis

• Anaerobes • H. influenzae • S. aureus

• P. aeruginosa

Structural lung disease (bronchiectasis, CF), recent broad spectrum antibiotics therapy, malnutrition, chronic steroids Age > 65; b-lactam therapy within 3 months; exposure to child in daycare; underlying medical co-morbidities

drug resistant S. pneumoniae

What are your basic Treatment Groups for Pneumonia?
1. No underlying. disease or modifying factors 3.

Inpatients not needing ICU care a. No comorbidities b. Underlying comorbidities 4. Severe pneumonia requiring ICU care a. Low risk for pseudomonas b. Risk for pseudomonas


Underlying comorbidities or modifying factors (COPD, CHF, alcoholism,…)

How do you treat each group?
Outpatient: No cardiopulmonary disease or modifying factors
Advanced generation macrolide (azithromycin, clarithromycin) OR Antipneumococcal fluoroquinolone (levofloxacin, moxifloxacin) Antipneumococcal fluoroquinolone OR 2nd/3rd generation cephalosporin + macrolide IV 3rd generation cephalosporin + macrolide OR IV antipneumococcal fluoroquinolone IV 3rd generation cephalosporin + macrolide OR IV antipneumococcal fluoroquinolone Consider Vancomycin (MRSA and PRSP) If there is a Pseudomonas risk, add these: Anti-pseudomonal B-lactam + cipro

Outpatient: With Cardiopulmonary Disease/Modifying Risk Factors Inpatient: Not needing ICU Inpatients: ICU requiring

HAP Pathogens and Treatment
• Treatment based upon the local hospital flora

Commonly available along w/ the drug resistances!

• Common pathogens:
         P. aeruginosa, Enterobacter, E. coli, Klebsiella, Proteus, Serratia, S. aureus, Acinetobacter, anaerobes

• HAP more likely to be polymicrobial • Resistant GN’s and S. aureus (MRSA) more common, and may spread rapidly to at risk patients

So in the Immunocompromised Host, what is reflective of the specific immune deficit? • Risk for pathogens reflect specific immune deficit
 Neutropenia:  bacteria,  aspergillus,  candida  Splenectomy:  encapsulated organisms  T-cell number (HIV) or function (immunosuppressives):  fungi,  mycobacteria,  viruses (CMV, EBV),  bacteria

HIV lung infections reflect what?
• Risk for infection proportional to CD4 count:
 >500: lower risk (M. tuberculosis, bacterial pneumonia)  <200: Pneumocystis carinii  <50: disseminated M. avium complex

• Higher frequency of bacterial pneumonia, esp. S. pneumoniae and H. influenzae, and tuberculosis at all CD4 counts • How do you avoid PCP in HIV+ patients?
 Prophylactic therapy in compliant patients quite effective  trimethoprim/sulfa – also used to treat  Dapsone  inhaled pentamidine – also used to treat

AIDS and Pneumocystis carinii
• Clinical Presentation
 Dyspnea, dry cough, fever – insidious onset  Diffuse infiltrates typical (normal in 5%; atypical with inhaled pentamidine)  Hypoxemia prominent feature

• Diagnosis
 Visualization (DFA, silver stain) of organisms in lower resp. secretions (induced sputum; bronchoalveolar lavage 85-95% sensitive in HIV)

• Treatment:
 Trimethoprim-Sulfamethoxazole (Bactrim)  IV pentamidine  Corticosteroids: for pO2 < 70 mmHg or A-a grad >35 mmHg (reduces risk of resp. failure and death)

AIDS and Non-TB mycobacteria
• Primary species are within M. avium complex • Risk when CD4 count < 50 (prophylaxis with clarithromycin) • Primarily cause disseminated disease, rather than pulmonary disease
 Fever, weight loss, anemia/leukopenia, diarrhea, hepatitis, adenopathy  MAC cultured from blood, bone marrow, stool

• Treated with Clarithromycin + ethambutol

AIDS and Fungal Pneumonia
• Cryptococcus neoformans:
 Common cause of meningitis, usually without pneumonia  May cause local or diffuse pulmonary disease; disseminate

• Histoplasmosis, Coccidiodomycosis:
 Usually disseminated disease in HIV

• Invasive Aspergillosis:
 End-stage (CD4 < 50) disease, concomitant neutropenia (e.g. meds…) are risk factors

AIDS and Non-infectious Lung Diseases
• Kaposi’s sarcoma: infiltrates, nodules, pleural effusions, adenopathy, and airway lesions all possible (Gallium scan negative)
 human herpesvirus-8

• Lymphocytic interstitial pneumonitis (LIP)
 especially children with HIV

• Non-specific interstitial pneumonitis (NSIP) • Pulmonary Hypertension
 Pathology identical to primary pulmonary hypertension

What is bronchiectasis? 2 modes of pathogenesis? Its vicious cycle?
“Irreversible dilation of airways caused by inflammatory destruction of airway walls”
Pathogenesis  Infection/Inflammation

bacterial pneumonia, tuberculosis, measles, pertussis

 Airway obstruction

Cystic Fibrosis (CF)  Primary Ciliary Dyskinesia (PCD; Kartagener’s Syndrome)  Hypogammaglobulinemia • Airway obstruction/Infection (total; IgG2/IgG4; IgA)  Airway wall damage/dilation  Impairment of mucus clearance  Promotion of Airway Infection

Other Etiologies of Bronchiectasis
 ―Traction bronchiectasis‖ - ILD  Airway obstruction (e.g. foreign body)  ABPA (Allergic bronchopulmonary aspergillosis)  1-antitrypsin deficiency  COPD  Rheumatologic diseases (Sjogren’s syndrome, RA)  Young’s syndrome (bronchiectasis, obstructive azoospermia, sinusitis; normal sweat Cl- and CFTR genotype)

• What happens to the bronchial arteries in bronchiectasis and why?
 Marked hypertrophy of bronchial arteries due to chronic inflammatory stimuli

Clinical features of bronchiectasis
• Chronic cough • copious purulent sputum production
 ~10% with ―dry bronchiectasis‖

• Periodic hemoptysis
 May be massive, as source is hypertrophied bronchial arteries, which are at system blood pressure

• Abnormal lung sounds and clubbing variably present What is suggestive history of bronchiectasis? How do we diagnose bronchiectasis?
HRCT – procedure of choice to demonstrate presence, location, and extent of disease

So you have a pt and the HRCT shows bronchiectasis. Now what?
• Figure out what the cause is!
 CF:

Sweat chloride or CFTR genotyping

 Immunoglobulin deficiency:

IgG/subclasses, IgA
nasal scrape for cilia structure; exhaled NO level

 PCD:

 1-antitrypsin  ABPA:

immediate aspergillus skin test; IgE • Treatment?
 Antibiotics aimed at airway flora  Airway clearance

 b-agonists

Chest percussion (manual, devices), exercise

Reduces reversible airway obstruction and promotes mucociliary clearance

 Surgery

Cystic Fibrosis
• What are the major defects?
 Production of thick, tenacious secretions from exocrine glands  Elevated concentrations of Na2+, K+, and Cl- in sweat

• What are the major clinical problems from CF?
 Pancreatic insufficiency  Recurrent episodes of tracheobronchial infections  Bronchiectasis

• What is the genetic basis of CF?
 Most common lethal genetic disease in Caucasian population

Affects 1 : 3,300 Caucasian births

 Monogenetic, autosomal recessive  Affected gene is called ―Cystic Fibrosis Transmembrane Conductance Regulator‖, or CFTR.  >1000 individual CFTR mutations identified, but DF508 mutation accounts for 2/3 of CF alleles worldwide

What is the Cascade to Lung Disease in CF?
CFTR Gene Mutation Altered Ion Transport
Abnormal airway surface liquid (volume depletion) Impaired airway defenses (reduced mucociliary clearance) Chronic airway infection/inflammation

Progressive bronchiectasis
Sodium is reabsorbed WAY too much from the airways. Water follow inwards. This leads to the collapse of mucociliary clearance.

How do you diagnose CF?
• 1+ typical phenotypic features and evidence of CFTR malfunction
 CFTR malfxn:  Sweat Chloride Test – gold standard; > 60 mmol/L  CFTR Mutation Analysis – genotyping; 2 mutations required  Nasal Potential Difference (PD) testing – demonstrates ion transport abnormalities  Phenotypic features:  Chronic Sinopulmonary Disease:




Persistent infection with P. aeruginosa, S. aureus Chronic cough/sputum PFTs (obstruction) Radiographs: bronchiectasis (upper lobe) Nasal Polyps, sinusitis Digital Clubbing





Meconium ileus, rectal prolapse, Distal Intestinal Obstruction Syndrome (DIOS) Pancreatic insufficiency Malnutrition Fat soluble vitamin deficiency Focal biliary cirrhosis Salt loss syndromes: acute salt depletion, chronic metabolic alkalosis Obstructive azoospermia (CBAVD)



How do you get pseudomonas in CF?
 Impaired mucociliary clearance  Static, hypoxic mucus layer  Pseudomonas growth in biofilms by altering metabolism from aerobic  anaerobic  Intense inflammation with resolution of infection

• What are serious complications of CF?
 Pneumothorax  Massive hemoptysis due to dilation of bronchial arteries  Respiratory insufficiency  Cor pulmonale

What is the standard maintenance therapy for CF?
• Airway obstruction from thick secretions
    Airway clearance DNase, mucolytics Hypertonic saline – speeds up clearance of mucus Bronchodilators

• Infection
 Inhaled and oral antibiotics

• Inflammation
 Ibuprofen  Corticosteroids  Azithromycin – also an antibiotic! Shown to slow disease

• Nutritional Support
 High fat/calorie diet  Pancreatic enzyme supplementation  Fat soluble vitamin supplementation (A,D,E,K)

• Screening for other complications
 CF-related diabetes  Liver disease  Bone disease

Occluded artery

Parenchymal infarct with hemorrhage

Pulmonary Thromboembolism

Pulmonary Thromboemboli (pulmonary embolism, PE)
• Clinical:
 Dyspnea, hemoptysis  Commonly due to lower extremity thrombi

• Radiology:
 Decreased flow, V/Q mismatch  abnormal V/Q scan

• Pathology:
 Pulmonary arterial thromboemboli  Survivors may have peripheral wedge-shaped infarction

Medial and intimal hypertrophy Plexiform lesion

Pulmonary Artery Hypertension
• Clinical:
 Sporadic Primary PH: Idiopathic; young adults; 5%  Familial Primary PH: Autosomal dominant; 5%  Secondary PH: Identifiable cause of increased pulmonary blood flow and/or increased resistance; 90%

• Radiology:
 Non-specific

• Pathology:
    Medial hypertrophy intimal proliferation intimal fibrosis plexiform vascular lesions




Elastica disruption = vascular injury Hemosiderin-laden macrophages = prior hemorrhage

Wegener’s Granulomatosis

What are the 2 Mechanisms That are Used when there’s increased blood flow through the lungs?

What’s going on with the pulmonary vasculature resistance as you inhale? • Total pulmonary vasculature resistance increases as you inhale/increase lung volumes
 Alveolar components increase with inspiration  Extra-alveolar components decrease w/ inspiration

• How do you define pulmonary hypertension?
 Defined as mean pulmonary artery pressure >25 mm Hg at rest or 30 mm Hg during exercise

• What is the general progression of disease w/ increased pulmonary vasculature resistance?
 Pulmonary vascular obstruction  increased pulmonary vascular resistance  pulmonary HTN  increased RV work  cor pulmonale

What is the vicious cycle of pulmonary HTN?

Pulmonary HTN

Decreased CrossSectional Area
Vascular Changes
Intimal proliferation Medial hypertrophy
Angiomatoid transformation Fibrinoid necrosis

What are the Mechanisms of Pulmonary Hypertension
• Passive:
 increased left atrial pressure, e.g. mitral stenosis, mitral regurgitation, LV failure

• Hyperkinetic:
 high flow states: VSD, ASD

• Occlusive:
 Chronic PE

• Obliterative:
 emphysema, interstitial lung disease, vasculitis, sarcoidosis

• Vasoconstrictive:
 hypoxia, scleroderma

What is the basis of Primary Pulmonary Hypertension
• Potential etiologies
       PGIS, endothelin, Kv-channels, eNOS, mutant BMPR2, ANP

• • • • •

Mean age at diagnosis is 36 More common in females than males No racial predilection Familial Disease accounts for ~10% of cases Disease progresses to cor pulmonale and premature death if not treated with median survival of 2.5-3 years

Symptoms of PPH
 Progressive exertional dyspnea—virtually 100%

Patient may faint upon exercise

      

Fatigue Chest pain—due to right ventricular Ischemia Exercise syncope or near syncope Hemoptysis Hoarseness Peripheral edema

• Physical Exam Findings
Jugular venous distention Accentuated second heart sound (P2) Right ventricular heave @ left sternal border Right sided gallops (S3, S4) @ sternal border Tricuspid regurgitation murmur (systolic) or pulmonic (diastolic) murmur  Peripheral edema due to RHF     

Therapy of Pulmonary Hypertension
 Anticoagulation– improves survival  Oxygen – in hypoxemic patients  Ca2+ channel blockers – may improve exercise tolerance and hemodynamics in patients (~25%) with mild-moderate disease  Prostacyclin—intravenous/subcutaneous administration improves hemodynamics, exercise tolerance, and prolongs survival in severe PPH  Bosentan—endothelin receptor antagonist that improves exercise tolerance.  Transplantation – the last resort

What are the Pathophysiological Consequences of Pulmonary Embolism

• Pulmonary consequences
      Increased alveolar deadspace Pneumoconstriction—described in animals Hypoxemia—shunt, V/Q mismatch Hyperventilation Depletion of alveolar surfactant—takes ~24 hr Pulmonary infarction

• Hemodynamic consequences
 Decrease in x-section area of pulmonary vascular bed:

50-60% reduction  significant pulmonary HTN, RHF, hypotension

 Humoral reflex mechanisms—hypoxic vasoconstriction, mediator release (like 5HT)

Diagnostic Tests for DVT

• • • • •

Venography Impedance Plethysmography Duplex Scanning Dopper flow velocity MRI scans


     

Diagnosis of Acute Pulmonary Embolism

Dyspnea Pleuritic pain Apprehension Cough Hemoptysis Syncope
Tachycardia Increased P2 Thrombophlebitis – in lower extremeties S3,S4 gallop Diaphoresis Edema Murmur Cyanosis


       


Laboratory Studies
    ECG- non-specific, sign of Right heart strain S1Q3 pattern in precordial leads CXR Blood Gases D-Dimers – more useful to r/o

• • •

Ventilation Perfusion Scanning – w/ good sxs, it’s fairly reliable Spiral or helical CT scanning Pulmonary Angiography

Contraindications to Heparin Therapy

• Absolute:
 Recent (w/in two weeks) hemorrhagic CVA.  Recent neurosurgery, ocular or spinal surgery

• Relative:
 Recent major surgery  Major trauma  Intracranial neoplasm  Recent gastrointestinal bleeding  Concurrent guaiac positive stool  Mild to moderate hemostatic defects  Severe uncontrolled hypertension >200mm Hg Systolic or >110mm Hg diastolic  Hematuria • In these situations, you would use an IVC!

So you’ve got edema in the distal airways and alveolar epithelium. What cell helps you deal? • TYPE II pneumocytes (main cell)
 By increasing Na-K ATPase on basolateral surface, you can increase influx of Na+ from the airspaces via ENaC  Water follow Na+  Na-K ATPase is inhibited by oubain  ENaC is inhibited by amiloride  This process is accelerated by beta-agonists  Can upregulate in at risk infants w/ corticosteroids to mom and infant  more type II cells  more surfactant and more efflux  Dexamethasone also helps increase expression of ENaC

• How can you measure the efficacy of alveolar fluid clearance in the lung?
 Inject a mix of regular and radioactive albumin

Fibrin-rich “hyaline membranes”

Alveolar filling pattern with air bronchograms

Exudative (Acute) Phase Diffuse Alveolar Damage (DAD)
• Clinical:
 Adult respiratory distress syndrome (ARDS)  Identifiable lung injury 0-2 wks before  Acute dyspnea, hypoxemia, decreased compliance

• Radiology:
 Diffuse alveolar filling pattern

• Pathology:
 Endo- or epithelial injury, Type II cell hyperplasia  First 2 wks after injury: edema  fibrin

Respiratory distress syndrome of newborns
• Clinical:
 Prematurity  Tachypnea, intercostal muscle retraction, hypoxemia

• Radiology:
 Diffuse alveolar filling pattern with air bronchograms

• Pathology:
 Insufficient surfactant production by type II cells  Atelectasis  hypoxia/acidosis  epith necrosis  Diffuse intra-alveolar hyaline membrane formation (exudative DAD)

RBCs filling alveolar spaces

Alveolar Hemorrhage Syndrome

Causes of Alveolar Hemorrhage Syndrome

• Goodpasture’s syndrome • Acute lupus pneumonitis • Wegener’s granulomatosis

Goodpasture’s syndrome
• Clinical:
 Young adults, M>F

• Radiology:
 Diffuse alveolar pattern

• Pathology:
 Anti-basement membrane IgG antibodies damage pulmonary and renal basement membranes  Linear IgG and C’ deposition by ImmunoFluorescence and Electron microscopy  Anti-GBM IgG is detectable in serum

Acute lupus pneumonitis
• Clinical:
 Component of systemic lupus erythematosus (SLE)  Children & adults, F>M

• Radiology:
 Diffuse alveolar pattern

• Pathology:
 Necrotizing capillaritis due to immune complexes  Granular IgG/C’ deposition by IF and EM  ANA or anti-dsDNA Ab detectable in serum


Aspiration of cooked fat

• Clinical:
 Children - foreign bodies  Adults - gastric acid, food  Lipids, e.g. mineral oil laxatives or nasal drops (―exogenous lipid pneumonia‖)

• Radiology:
 Focal alveolar pattern  typically RLL

• Pathology:
 Gastric acid  DAD  Foreign material  foreign body giant cell reaction with exogenous material

Endogenous lipoid pneumonia
(“post-obstructive”, “golden” pneumonia)

• Clinical:
 Central major airway obstruction

• Radiology:
 Peripheral infiltrates +/- central mass

• Pathology:
 Increased numbers of foamy alveolar macrophages distal to an airway obstruction, +/- cholesterol clefts, without foreign material

Foamy Macrophages

Endogenous (Post-Obstructive) Lipid Pneumonia

Transudate in interstitium and alveolar airspaces

Capillary congestion

Severe Pulmonary Edema

Pulmonary Edema
• Clinical:
 Cardiogenic: LV pump failure, mitral valve stenosis

• Radiology:
 Incr. vascular markings, reticular +/- nodular  Think Kerley B lines

• Pathology:
 Venous and capillary congestion  Incr. free water in the interstitium +/- alveoli

Define ARDS
• Acute Respiratory Distress Syndrome – A clinical definition – Acute onset – Bilateral infiltrates on CXR – Pulmonary Artery wedge pressure <18 or no evidence of left atrial hypertension
• PaO2/FIO2 < 300: Acute Lung Injury • PaO2/FIO2 < 200: ARDS

• Common Causes? Most Common Cause?
Direct Lung Injury Pneumonia Aspiration Pulmonary Contusion Fat Emboli Inhalational Injury Near Drowning Indirect Lung Injury Sepsis Multiple Trauma Other Shock Acute Pancreatitis Multiple Transfusions Drug Toxicity

Septic Shock
Inflammatory Cytokines
Nitric Oxide from Vasc. Endothelium

Low Systemic Vascular Resistance High Cardiac Output Hypotension Wide pulse pressure ex: (90/30)
Brisk capillary refill

Decreased urine output Decreased mental status Lactic Acidosis –
b/c all these tissues are underperfused




Continuum and Definitions of Septic Shock

– Inflammatory response to microorganisms, or – Invasion of normally sterile tissues – Systemic response to a variety of processes
• • • • Fever, tachypnea, tachycardia, Leukocytosis


Systemic Inflammatory Response Syndrome (SIRS)

– Be careful; there are some infections that resemble sepsis but AREN’T despite the overlap with SIRS – It all comes down to is it multiorgan?!?!


– Infection plus – 2 SIRS criteria


Severe Sepsis

– Sepsis – Organ dysfunction (ex: hypotension, hypoxemia) – Sepsis – Hypotension despite fluid resuscitation
– Altered organ function in an acutely ill patient – Homeostasis cannot be maintained without intervention


Septic shock


Multiple Organ Dysfunction Syndrome (MODS)

Acute or Exudative Phase of ARDS
Exposure to a Risk Factor

Alveolar Capillary Injury

Epithelial Cell Injury

Leak of Protein Rich Fluid into Interstitium and Alveolus
Arterial hypoxemia refractory to oxygen = SHUNT! Bilateral patchy infiltrates VERY Decreased lung compliance (need PEEP) Rapid onset respiratory failure

Proliferative or Fibrotic Phase of ARDS
• Fibrosing Alveolitis
– Procollagen III peptide present day 1 or 2 – Histologic changes day 5-7

• Clinical Evidence Day 5-10
– – – – Persistent hypoxemia Increased alveolar dead space Further decrease in compliance Pulmonary hypertension - Obliteration of pulmonary capillary bed

• Steroids are helpful in this stage (but not in the acute/exudative phase) • When ventilating a patient, make sure you don’t overdo it
– You don’t want to injure the healthy parts of the lung – Use a low tidal volume at a higher frequency (despite the inability to get rid of CO2)

2 General Classes of Respiratory Failure
Hypoxemic - inadequate O2 delivery

Hypercapnic - respiratory acidosis (high PCO2)
secondary to failure to adequately ventilate

Hypoxemic Failure Physiological Causes
A. Decreased PIO2 B. Decreased VA
C. Ventilation/Perfusion [V/Q] Mismatch

D. RL Shunt E. Diffusion Limitation only problematic during exercise

Physiologic Causes of Hypoxemic Failure
• Decreased PIO2
– As with high altitude

• Decreased VA
– Hypoxia (PAO2) secondary from hypercapnia (PACO2)

• V/Q Mismatch
– Can be corrected by supplemental O2

• RL Shunt
– Refractory to O2 treatment

• Diffusion Limitation
– Only a problem under exercise stress due to increased CO (common in pulmonary fibrosis)

Physiologic Causes of Hypercapnic Failure
• Increased VE 2o  VCO2
– fever, trauma

• • •

Increased VE 2o  VD/VT
– – pulmonary embolism, emphysema Many, many causes
1. Respiratory drive (e.g., narcotic overdose) 2. Nerve conduction (e.g., cervical cord trauma, Guillain-Barre syndrome) 3. Neuromuscular (e.g., myasthenia gravis, muscle atrophy) 4. Chest wall (e.g., flail chest, kyphoscoliosis) 5. Lung disease (e.g., asthma, COPD) 6. Upper airway obstruction

Decreased VA Causes of Decreased Minute Ventilation

Arterial blood gases and diagnosis
pH 7.40
7.30 7.37 7.25

pCO2 HCO340
55 55 85

26 31 36

Acute Failure Compensated Failure Acute and Chronic Failure

Clinical signs of respiratory muscle weakness
1. Tachypnea

2. Decreasing Vital Capacity 3. Decreasing Maximum Inspiratory Force
4. Ineffective cough
Note: Hypercapnea is a late sign of respiratory failure due to neuromuscular limitations.

Support ventilation prior to Resp. Failure

How do you TREAT Hypercapnic Failure?
A. Diagnose and treat underlying cause B. Consider respiratory stimulants
1. Naloxone (opioid antagonist) 2. Controlled hypoxemia (in proper clinical settings) 3. Chemicals (rarely effective; xanthines, progesterone)

C. Assist devices
1. Negative pressure - Iron lung, Cuirass ventilator 2. Nasal/Face Mask CPAP - Continuous Positive Airway Pressure 3. Cycled CPAP (BiPAP) - Bilevel Positive Airway Pressure

D. Threshold for tracheal intubation and positive pressure ventilation usually low pH. E. Mechanical ventilation techniques
1. Breath initiation/Respiratory Rate 2. Tidal volume 3. Patient regulation of VE -Spontaneous breaths - Tidal volume 4. PEEP = Positive End Expiratory Pressure

Damage to these parts of the brain are associated with what types of breathing patterns?
• Forebrain
– Post hyperventilation apnea – Cheyne Stokes Respiraton:
• crescendo-decrescendo • Due to problems w/ CNS or HF

• Hypothalamus
– Central reflex hypernea

• Pons
– Apneustic breathing – pause btw inspiration and expiration – Cluster breathing – Ataxic breathing

• Medullary
– Ondine’s Curse – no involuntary control of breathing – Ataxic breathing

What is Sleep Apnea?
• • • Repetitive episodes of diminished air flow associated with oxygen desaturation or arousal Patients may have hundreds of events per night Two types:
– Obstructive
• You try to breath, but the airway is closed • Relaxation of upper airway muscles

– Central
• There is no stimulus to breath • Relaxation of lower airway muscles


Associated w/:
– – – – – – – Snoring Obesity (can still occur in normal body habitus) Mixed w/ Cheyne-Stokes or hypoventilation HTN Tachycardia Narrow airway, edema, large neck Risk factors: smoking, alcohol, GERD, brain disease, heart disease, ADHD (any kid who snores, evaluate!) – IS a risk factor for: HTN, MI, Stroke, RHF, pulmonary HTN, Diabetes, Motor vehicle accidents, HA, Depression, Shorter life span by 7-10yrs

Who needs evaluated for OSA ?
• Snoring associated with HTN, obesity, DM, or any vascular disease. • Snoring in individuals with unrefreshing sleep, excessive sleepiness or insomnia. • All children who snore (American Academy Pediatric).

OSA Treatment
• Continuous Positive Airway Pressure (CPAP, BiPAP) • Surgery – 50-50 chance of success • Dental Device • Weight Loss • Medication • Avoidance of alcohol • Sleep on side

Respiratory Failure
Lung Failure
Gas Exchange Failure Hypoxemia

Ventilation Failure Hypercapnia

Low Inspired O2 Diffusion Limit Shunt Poor VA VQ Mismatch

CNS Depression
Muscular Fatigue

Mechanical Failure

Causes of Hypercapnic Failure
• Normal Ventilation – Increased Production of CO2 (fever, tramua) • Normal Ventilation with Increased Deadspace (VQ Mismatch) – Pulmonary Embolus – Emphysema • Decreased Ventilation (lots of causes) – Breath Holding – Obesity – Drugs

What’s the Poor Mans Rule of Thumb for Acute versus Chronic Respiratory Acidosis?
• Acute Respiratory Acidosis
-HCO3 rise by 1 mEq/L for each 10 mmHg PCO2

• Chronic Respiratory Acidosis
-HCO3 rise by 4 mEq/L for each 10 mmHg PCO2
– The body has had time to renally/metabolically compensate for the respiratory acidosis by increasing HCO3- amts to counteract the drop in pH.

What are the causes of dyspnea?
• Abnormal gas exchange or acidosis
– Hypercapnia – sensed in medulla, carotid bodies – Hypoxemia – sensed in carotid bodies – Low pH - sensed in medulla, carotid bodies

• Increased neuromuscular stimuli
– Chest wall muscle receptors – Parenchymal and airway receptors

• Abnormal perception/psychogenic

If given these Sxs in the history, what diseases should you be thinking about?

If given these findings in the physical exam, what diseases should you be thinking about?

If given these findings in the physical exam, what diseases should you be thinking about?

If given these findings in the physical exam, what diseases should you be thinking about?

If given these diagnostic results, what diseases should you be thinking about?

What are these diagnostic tests useful for in making diagnoses?

Congrats! You’re Done!
Good luck on the exam &

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