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

Shunt
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

V/Q mismatch
Shunt

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

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

Obesity?

FRC reduced

Inspiratory muscle weakness?

TLC reduced

Expiratory muscle weakness?

RV is elevated

Mechanisms of Hypoxemia

Hypoventilation
V/Q Mismatch
Shunt
Low Inspired pO2

How do we measure lung volumes?

Helium dilution

Used to measure absolute FRC

Doesnt work if theres lots of obstructed airways where a

Plethysmography

The small sealed box

Makes measurements using Boyles law

What patterns of impairment

are associated with:
Obstructive lung disease?
Diminished rates of expiratory flow (increased FEV 1,
decreased FEV1/FVC)

Restrictive lung disease?

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 its an extra-thoracic variable obstruction

When is obstruction increased during expiration?

When its an intra-thoracic variable obstruction

Normal
WhatsAlveoli!
this?

Dilated bronchi

Muco-Purulent Debris in Dilated Bronch

Bronchiectasis

Bronchiectasis
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 (Kartageners 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

Eosinophil

What disease is this?

Charcot-Leyden crystals eosinophil granule contents

This is ASTHMA!!!!

Asthma
Curschmann Spirals mucus
casts

Asthma
Clinical:

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

Radiology:

Alternating atelectasis and overexpansion

Pathology:

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

Chronic Bronchitis
Increased numbers of mucinous glands in submucosa

A Clinical Diagnosis!

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:

Centrilobular

Emphysema in COPD

Emphysema
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?

Eosinophils (in sputum)

B lymphocytes in mediating the asthma more impt

Whats the point of the methacholine challenge?

It demonstrates that theres something different in the

architecture of the asthmatics airways that makes them nonspecifically hyperreactive

What is a key feature of the pathophysiology of asthma

that contributes to death?
Mucous plugs occluding airways

What are Creola bodies?

Agglomerated bronchial epithelial cells, seen in asthma

What happens when you administer a beta-agonist?

You initially decrease the O 2 saturation via V/Q mismatch.

What is AM dipping?

When peak flow is decreased in the morning; associated w/ more

severe asthma

What is the late phase reaction?

Delayed reduction in FEV1 due to IgE and influx of inflammatory
cells

What is the cornerstone of asthma therapy?

Corticosteroids (effective in reducing late phase reaction)

1.

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

2.
3.

Auto peak end expiratory pressure (auto-PEEP)-with

rate respiratory rate.
DLCO
Increased - useful in establishing dx

4.

Methacholine challenge
Hyper-responsive

5.

b-agonist
Reversible airflow obstruction when treated; albuterol

6.

Eosinophils
Increased in blood and found in sputum

7.

ABG
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 cant 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 PO 2, 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

Whats 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

Feature

Pink Puffer

Blue Bloater

Pathophys.

Type A

Type B

Disease
Association

Emphysema

Chronic Bronchitis

Major Sxs

Dyspnea

Cough & sputum

Appearance

Thin, wasted

Cyantoic, obese

PO2

Decreased

Decreased

PCO2

Normal or
decreased

Normal or
increased

Elastic recoil

Decreased

Normal

DLCO

Decreased

Normal

Hematocrit

Normal

Increased

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 dont 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 its 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/doesnt

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

What disease?
Sarcoidosis

 Clinical:
o
o
o

Sarcoidosis

Multi-system granulomatous disease

Adults, B>W, F>M
Dyspnea

Radiology:
o

Interstitial infiltrates in bronchovascular distribution (= lympagenic

distribution)
Usually have hilar adenopathy (picked up on routine CXR)

Pathology:
o
o

Tight, well-formed non-caseating granulomata

Def of granulomata: Focal accumulations of epithelioid histiocytes

Loose
Granulomas

Hypersensitivity
Pneumonia

Interstitial expansion

Peri-Bronchiolar
Expansion

Hypersensitivity Pneumonitis
(Extrinsic Allergic Alveolitis)
Clinical:
o

Organic dusts

o
o

Doesnt mean carbon based

Means related to organic products

Occupational or environmental exposure

Acute and chronic: dyspnea, cough, fatigue

Radiology:
o

Bilateral interstitial linear or nodular pattern

Pathology:
o

Patchy peri-bronchiolar and interstitial chronic inflammation with

loosely formed granulomata

Coal dust macules

Coal-workers Pneumoconiosis

Patchy Sub-Pleural Fibrosis

Ferruginous Body

Asbestosis

Fibrotic Nodules

Late Silicosis

UIP: Sub-pleural fibrosis adjacent to normal lung

UIP

Usual Interstitial Pneumonia

(UIP)

Clinical:
o
o

Syn. with Idiopathic pulmonary fibrosis (IPF)

Adults, mean 51 yo; poor response to steroids, 66% mortality

Radiology:
o

Patchy subpleural infiltrates, DDx asbestos, rheum

Pathology:
o

o
o

Patchy interstitial inflammation; fibrosis alternating with

normal parenchyma
Temporally heterogeneous = ongoing injury to lung
Morph overlap with rheum dzs, e.g. scleroderma

Fibroblasts in the interstitium

Alveolus

Proliferative phase DAD

Proliferative (Organizing)
Phase Diffuse Alveolar
Damage (DAD)

Clinical:
o
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

Radiology:
o

Diffuse, interstitial>alveolar pattern

Pathology:
o
o

Interstitial + intra-alveolar fibroblastic proliferation

Temporally uniform

If its temporally heterogeneous = UIP

You HAVE to see interstitial fibroblastic proliferation

If its purely intra-alveolar = BOOP

What characterizes Pulmonary

function in Restrictive Lung Disease?
o

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
TLC
TLC
FRC
FRC
RV

TLC
FRC
RV

TLC

FRC
RV

RV

 Whats the differential diagnosis for bilateral diffuse infiltrates that

mimic diffuse parenchymal disease?
o
o
o

Congestive heart failure

Pulmonary infection
Lymphangitic carcinomatosis

What are known causes of diffuse parenchymal lung disease?

o
o
o

Inhaled organic dusts (asbestosis, silicosis, coal workers, berylliosis

Inhaled organic antigens hypersensitivity pneumonitis
Iatrogenic (drugs amniodirone, radiation)

What are unknown etiological diffuse parenchymal lung diseases?

o
o
o
o
o
o

IPF/UIP
Sarcoidosis
BOOP
Goodpastures
Wegeners
And many more (Connective tissue disease associated, Chronic eosinophilic
pneumonia, Lymphangioleiomyomatosis, Pulmonary Langerhans cell
histiocytosis, Alveolar proteinosis, Pulmonary vasculitides)

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

Reduced FVC, reduced FEV1, normal ratio

Reduced lung volumes TLC, FRC, RV

Diffusion impairment
o

Destruction of alveolar-capillary interface by inflammation and

fibrosis, reducing the surface area for gas exchange (there is a
reduced DLCO on testing)

Pulmonary Hypertension
o
o

Hypoxemia
Obliteration of small pulmonary vessels by fibrosis

Clinical Features of
Parenchymal Lung Diseases
Symptoms
o
o

Dyspnea
Cough (non-productive)

Signs
o
o
o

Dry crackles or rales (sound like velcro)

Clubbing
Cor pulmonale

JVD
Loud P2, TR murmer
edema

 Whats 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?

o

A chronic systemic granulomatous idiopathic disease where theres

an immune response to an exogenous agent in a genetically
predisposed individual

What key cells are thought to be involved in sarcoidosis?

o

Macrophages

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?
o

Lofgrens

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

Lupus pernio

Associated with chronic sarcoidosis

Usually on face, sometime butt and extremities

 What are common abnormalities/diagnostic test results in

sarcoidosis?
o

o
o
o
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
o

Systemic corticosteroids
anti-TNF may be best tx (infliximab)
hydroxychloroquine

What is the staging of sarcoidosis?

o
o
o
o

Stage I adenopathy
Stage II parenchymal infiltrates & adenopathy
Stage III just parenchymal infiltrates
Stave IV fibrosis, hilar retractionm, cysts, bullae, honeycombing
changes

UIP/IPF
Pathogenesis?
o

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?

o

Older adults, M>F

Signs and Symptoms?

o
o
o

Exertional dyspnea that increases over time

Non-productive cough
Possible clubbing

 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

HRCT

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?
o

Secretory Inflammation

Formaldehyde upper airways

Ammonia upper airways
Particulates (coal, dust, cotton) bronchitis
Nitrogen dioxide bronchiolitis

Hyperreactive Airways

Ozone, cotton dust non-specific reactivity

TDI occupational asthma

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 farmers lung (mold spores in hay)
Inorganic materials

Chronically

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?

o

Nodular or diffuse fibrosis

Silicosis
Asbestosis
Berylliosis
Coal Workers

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

I.

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

II.

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?
o

20-30days

Pathologic features?
o
o
o
o

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

Clinical Symptoms and CXR?

o
o
o
o
o

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

Occupational Asthma
Definition?
o

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
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

Standard Treatment:
o

Inhaled steroids and bronchodilators

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?
o

Caused by inflammatory processes that intensify upon breathing

Whats going on with a tension pneumothorax?

o
o

Air escapes into pleural space positive pressure

Air cant escape on exhalation

How can a tension pneumothorax cause shock?

o

By compromise of venous return

How can ANY pneumothorax be caused?

o
o
o
o

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 kind of pneumothorax?

o
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!

o
o
o

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

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?

o

On side of pneumothorax

Absent vascular markings

Appearance of a little nub near hilum (atelectic lung)
Diaphragm depressed downwards

On side opposite of pneumothorax

Mediastinum, trachea, other structures shifted over

Its a dark and stormy night And a patient is brought into your
ER with:

After youre told hes NOT possessed and isnt just freaked out
after watching that scary movie, you get a CXR.
That CXR shows:

Pleuritic chest pain

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

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!

DUH
How is normal pleural fluid made?
o

Generated by Starling forces across a capillary bed

Radiographic signs of pleural effusion include:

o
o
o
o

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

How do you relieve a massive pleural effusion?

o

Thoracentesis

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?

o

Make sure the fluid is freely flowing and not loculated

o
o

Use a lateral decubitus film

Use ultrasound to locate effusion

Be sure to draw close to the upper part of the rib directly below the
needle youre using, or you might hit an intercostal artery, vein,
nerve

What are Lytes 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
o

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
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

Causes of turbid exudates?

Chylothorax
Empyema

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 theres a good

exam question in here
o

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 its 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!

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

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

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

Implies active bacterial infection in the pleural space.

Failure to recognize & drain can lead to unresolved sepsis & fibro thorax

So how do I tell the difference between the two?

o

Well if its an empyema, there should be:

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

And if its all borderline you need to retap thatumlung

Ack! Its 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
Dont 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 dont 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!

Hamartoma
o
o

Its BENIGN!!!!
Clin:

Rad:

Adolescence adulthood
None in newborns - not congenital
Solitary nodule +/- popcorn calcification
Peripheral > central

Path:

Gross: solitary, lobulated, cartilagenous

Micro: normal tissues in excess/disarray
If its calcified, its 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 doesnt belong

Small cell is treated differently and has a much

more severe progression!

Desmosomes

Keratin

Squamous Cell Carcinoma

Normal

Squamous cell carcinoma

Clin:
o

Smokers association?

Prevalence?

YES
20-30% of common carcinomas

May secrete PTH-like compound

Radiology:
o

central > > peripheral

Path:
o

Bronchi > Larynx > Trachea

KEY CHARACTERISTICS?
+/- Desmosomes (intercellular bridges)
+/- Keratin production, e.g. keratin pearls

Primary
Gland formation

Adenocarcinoma
Pleural effusion
Mucin production (red on PASd stain)

Adenocarcinoma
Clin:
o
o

30-40% of common carcinomas

Smoking association?

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

occur in smokers

Rad:
o

peripheral > central

Path:
o +/- glands
o +/- mucin
o

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?
o

Adenocarcinoma

Incidence?
o
o

Rising incidence (presently 20-25%)

Associated w/ smoking?

Not associated with cigarette smoking

Rad:
o

Peripheral, can be multifocal and bilateral

Path:
o
o
o

Lepidic (butterfly-like) growth pattern

Mucinous or non-mucinous
Unifocal or multifocal

Large cell undifferentiated carcinoma

Large cell undifferentiated

carcinoma
o

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

its 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

Smokers?

o
o

20 % of common carcinomas
Paraneoplastic Syndromes:

o
o

YES

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

Commonly high stage at presentation

Responsive to chemo/RT, but low 5 yr survival

Rad:
o
o

Central in >90%
Frequent metastases to LNs and distant sites

Path:

Malignant cytology; high N:C ratio

No nucleoli; punctate salt and pepper nucleoli
High mitotic activity and tumor cell necrosis

Think small round blue cells!

o
o

Thin delicate microvilli

Associated w/ ferruginous bodies

Visible
CP
Angle

Mesothelioma

LossofCPAngle
Normalthicknesspleura
Thickenedpleura
=Pleuraleffusionormass

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?
o
o

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

What types of molecules are the predominant carcinogens in

cigarettes?
o

Polycyclic hydrocarbons

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

o
o
o

WOMEN
Differences in metabolism, CYP450
Hormonal effects in lungs

What are some mutations that have been implicated?

o
o
o
o
o
o

3p NSCLC
Ras adenocarcinoma
Myc small cell
NSCLC p53
Rb small cell
Random breaks in 1, 3, 5, 7, 15, 17

More Lung Cancer Basics

Most common sites of metastases:
o
o
o
o

Liver
Bone
Brain
Adrenals

What are the paraneoplastic syndromes associated w/

NSCLC?
o

Clubbing, Hypertrophic orthropathy (adeno), Hypercalcemia

(squamous)

What are the paraneoplastic syndromes associated w/

SCLC?
o

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 Ca2+

The Good, Special Stuff

o

For central, endobronchial lesions

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
SCLC
o

Whats 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

Whats not so useful?

TNM system (which is used in NSCLC)

T location, size
N nodes
M metastases
-

IIIA, IIIB = locally

advanced
IIIB, IV =
advanced, effusion

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

 Tricks to help us stage NSCLC?

o

Intrathoracic

Chest CT
FDG PET Scan
Mediastinoscopy

Extrathoracic

Bone scan
CT/MRI of brain
Abdominal CT (liver, adrenals)
Biopsies of extrathoracic lesions

Treating NSCLC
o
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

Bronchioloalveolar carcinoma

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

 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

Small Cell Lung Cancer

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)

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 doesnt have normal blood flow for tx

with antibiotics AND it doesnt 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 thats where
aspiration goes!

An abscess.
Whos 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)

Tuberculosis
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 its
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)

Histoplasmosis
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

Coccidioidomysis
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

Cryptococcosis

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

Blastomycosis
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

Aspergillosis
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

Allergic-Bronchopulmonary aspergillosis (ABPA)

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
Its not the fungus that hurts you, its your bodys response

Invasive aspergillosis usually fatal

Almost exclusively in immunocompromised hosts

Invasion of pulmonary blood vessels with
organismcausing infaction, thrombosis, exsanguination

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

Mucomycosis

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

Mycoplasma
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
Youll see something on CXR but not lots of sxs
Really common at college/in dorms

What are common host defenses to

respiratory infection?
ANATOMIC

Upper Airway (nose)

Epiglottis/Larynx
Epithelial Tight Junctions

MECHANICAL (INNATE)

Mucociliary and Cough Clearance

IMMUNE

Innate (lysozyme; lactoferrin; defensins)

Immune Response

Secretory IgA (nasal/bronchial)

Humoral Antibody
Cellular

GENERAL

Alveolar Macrophages (AM)

Inflammatory Response (PMNs, etc.)
Anti-Proteases

 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 whats 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

NOT HIGHLY PREDICTIVE OF SPECIFIC PATHOGENS!!!

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 wont tell you what the
responsible pathogen is

Since CXR and clinical presentation only

tells you the patient has pneumonia, do
you even care what the causative microbe
is?
YES
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 Grams 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 youve got
Large numbers of bacteria with a single morphology
observed in setting of many PMNs and few/no
squamous epithelial cells (i.e. lower airway specimen)
Obtained before antibiotics
Detection of a non-colonizer (mycobacteria, endemic
fungi, Legionella, PCP)
Thats when I go:

Yeeeeeeeearrrrrrhhhhh!!!
(yes I know Im a dork, but youre 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

persons mistake, you see
this. What are you thinking?

Besides thinking damn, Im 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. Youll assess the severity looking at
what? And
whatll make you panic?

Demographics:

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

Alcoholism, nursing home, cariopulmonary disease

like Klebsiella

Anaerobes

Loss of consciousness (alcohol, seizure), swallowing

dysfunction, poor dental hygiene, airway obstruction

H. influenzae

COPD, smoker

S. aureus

Nursing home, post-influenza, IVDA, bronchiectasis

P. aeruginosa

Structural lung disease (bronchiectasis, CF), recent

broad spectrum antibiotics therapy, malnutrition,
chronic steroids

DRSP

Age > 65; -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?
Outpatient
1.

No underlying. disease or
modifying factors

2.

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

Inpatient
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

How do you treat each group?

Outpatient: No cardiopulmonary
disease or modifying factors

Outpatient: With
Cardiopulmonary
Disease/Modifying Risk Factors

Advanced generation macrolide

(azithromycin, clarithromycin)
OR
Antipneumococcal fluoroquinolone
(levofloxacin, moxifloxacin)
Antipneumococcal fluoroquinolone
OR

Inpatient: Not needing ICU

2nd/3rd generation cephalosporin +

macrolide
IV 3rd generation cephalosporin + macrolide

Inpatients: ICU requiring

IV antipneumococcal fluoroquinolone
IV 3rd generation cephalosporin + macrolide

OR

OR
IV antipneumococcal fluoroquinolone
Consider Vancomycin (MRSA and PRSP)
If there is a Pseudomonas risk, add these:
Anti-pseudomonal B-lactam + cipro

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 GNs 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
Kaposis 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; Kartageners
Syndrome)
Hypogammaglobulinemia (total; IgG2/IgG4; IgA)
Airway obstruction/Infection
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 (Sjogrens syndrome, RA)
Youngs 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

PCD:

nasal scrape for cilia structure; exhaled NO level

1-antitrypsin
ABPA:

immediate aspergillus skin test; IgE

Treatment?

Antibiotics aimed at airway flora

Airway clearance

Chest percussion (manual, devices), exercise

-agonists

Reduces reversible airway obstruction and promotes

mucociliary clearance

Surgery

For refractory symptoms/hemoptysis from localized disease

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:

GI:

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

Others:

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

Necrotizing

Granulomatous

Vasculitis

Elastica disruption = vascular injury

Hemosiderin-laden macrophages = prior hemorrhage

Wegeners Granulomatosis

What are the 2 Mechanisms That are

Used when theres increased blood flow
through the lungs?

Whats 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 dyspneavirtually 100%

Patient may faint upon exercise

Fatigue
Chest paindue 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 mildmoderate disease
Prostacyclinintravenous/subcutaneous
administration improves hemodynamics, exercise
tolerance, and prolongs survival in severe PPH
Bosentanendothelin receptor antagonist that
improves exercise tolerance.
Transplantation the last resort

What are the Pathophysiological

Consequences of Pulmonary Embolism
Pulmonary consequences

Increased alveolar deadspace

Pneumoconstrictiondescribed in animals
Hypoxemiashunt, V/Q mismatch
Hyperventilation
Depletion of alveolar surfactanttakes ~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 mechanismshypoxic vasoconstriction,

mediator release (like 5HT)

Diagnostic Tests for DVT

Venography
Impedance Plethysmography
Duplex Scanning
Dopper flow velocity
MRI scans

Diagnosis of Acute Pulmonary Embolism

Symptoms

Signs

Tachycardia
Increased P2
Thrombophlebitis in lower extremeties
S3,S4 gallop
Diaphoresis
Edema
Murmur
Cyanosis

Laboratory Studies

Dyspnea
Pleuritic pain
Apprehension
Cough
Hemoptysis
Syncope

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, its 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 youve 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

Goodpastures syndrome
Acute lupus pneumonitis
Wegeners granulomatosis

Goodpastures 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

Lipid
Aspiration of cooked fat

Aspiration
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)

Decreased urine output

Brisk capillary refill

Decreased mental status

Hyperdynamic

Lactic Acidosis
b/c all these tissues are underperfused

Continuum and Definitions of

Septic
Shock
Infection

Systemic Inflammatory Response Syndrome (SIRS)

Inflammatory response to microorganisms, or

Invasion of normally sterile tissues
Systemic response to a variety of processes

Fever,
tachypnea,
tachycardia,
Leukocytosis

Be careful; there are some infections that resemble sepsis but ARENT despite the
overlap with SIRS
It all comes down to is it multiorgan?!?!

Sepsis

Severe Sepsis

Septic shock

Multiple Organ Dysfunction Syndrome (MODS)

Infection plus
2 SIRS criteria
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

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 dont overdo it
You dont 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. RL 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

RL 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

Increased VE 2o VD/VT

pulmonary embolism, emphysema

Decreased VA

fever, trauma

Many, many causes

Causes of Decreased Minute Ventilation

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

Arterial blood gases and diagnosis

pH

pCO2 HCO3-

7.40

40

24

Normal

7.30

55

26

Acute Failure

7.37

55

31

Compensated Failure

7.25

85

36

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
Ondines 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
Low Inspired O2
Diffusion Limit
Shunt
Poor VA
VQ Mismatch

Ventilation Failure
Hypercapnia

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

Whats 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!
Youre
Done!
Good luck on the exam
&