1

Pathophysiology: Lung Formulas to Memorize ............................................................................................................................................................ 2

Lung Mechanics Review .......................................................................................................................................................... 3

Reading a CXR ......................................................................................................................................................................... 5

Pulmonary Function Testing ................................................................................................................................................... 6

Interstitial Lung Disease ........................................................................................................................................................ 10

COPD ..................................................................................................................................................................................... 13

Pathophysiology of Asthma .................................................................................................................................................. 17

Expiratory Flow Limitation .................................................................................................................................................... 21

Pulmonary Vascular Disease ................................................................................................................................................. 24

Obesity & Breathing Disorders.............................................................................................................................................. 27

Ventilatory Failure ................................................................................................................................................................ 30

Acute Respiratory Distress Syndrome (ARDS) ...................................................................................................................... 34

Pneumonia ............................................................................................................................................................................ 37

The Pleural Space .................................................................................................................................................................. 44

Bronchopulmonary Dysplasia ............................................................................................................................................... 48

Cystic Fibrosis ........................................................................................................................................................................ 52

Disorders of the Lower Airways ............................................................................................................................................ 56

Upper Airway Disorders ........................................................................................................................................................ 61

2

Formulas to Memorize

Alveolar gas equation: 𝑷𝑨𝑶𝟐 = 𝑭𝑰𝑶𝟐 × 𝑷𝑩 − 𝟒𝟕 − (𝑷𝒂𝑪𝑶𝟐

𝟎.𝟖)

If on room air: simplify it! 𝑷𝑨𝑶𝟐 = 𝟏𝟓𝟎 − (𝑷𝒂𝑪𝑶𝟐

𝟎.𝟖)

Use to calculate A-a difference (alveolar – arterial)

Normal values: < 20 on room air (20% O2) < 100 on 100% O2

Increase: suggests venous admixture (poorly oxygenated blood reaching circulation)

Arterial Blood Gases: know normal values

pH 7.35-7.45 PaO2 80-100 mm Hg PaCO2 35-45 mm Hg

PAO2 Alveolar O2 tension

FIO2 Fraction inspired O2

PB Barometric pressure (corrected for water pressure, - 47)

PaCO2 Arterial CO2

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Lung Mechanics Review Note: there’s probably way more to review than this lecture covered

Transmural pressure = pressure inside – pressure outside Transpulmonary pressure (PL)= (alveolar pressure) – (pleural pressure) = elastic recoil pressure Transdiaphragmatic pressure (Pdi) = abdominal pressure = pleural pressure PBS = body surface pressure, Ppl = pleural pressure, PCW = chest wall pressure So the pressure across the respiratory system is PL – PCW = (Palv – Ppl) – (Ppl – Pbs) =

PRS = Palv - Pbs Compliance: slope of the pressure-volume curve

Compliance = ΔV / ΔP Elastance = 1/compliance

o high compliance = very distensible, high elastance means very stiff o Compliance is better term

Graph

o Note that compliance isn’t linear

changes with volume (less compliant at higher volumes)

o Volume at zero transmural pressure: residual volume (unstressed volume)

Unstressed volume (relaxation volume) volume in an elastic structure when transmural pressure = 0

Stressed volume volume above the unstressed volume which distends the surface

Lung Compliance

Note that RV is the volume that remains in lung at Tm = zero

Lung is less compliant at higher volumes

Some disease processes make lung:

more compliant (emphysema)

less compliant (fibrosis) What determines lung compliance?

Tissue properties (elastin, collagen, etc.)

Surface tension: wherever an air-liquid interface exists, there’s a net attractive force that tends to collapse the bubble

o Fill lung with saline: Less pressure needed to inflate (more compliant – no surface tension)

o Surfactant: reduces surface tension & stabilizes alveoli o ARDS: loss of surfactant = less compliant lung

Hysteresis: the compliance curve is different on inspiration vs expiration

Convention: compliance = expiratory compliance

Why? Harder to inflate than keep inflated o surfactant o lung units close on exhalation & takes extra work to pop them back open o tissue relaxes after time in stress & loses recoil

4

Chest Wall Compliance This curve only applies when chest wall TOTALLY RELAXED

Don’t measure in pulmonary function lab – can’t totally relax

Less compliant at lower volumes (rib joints, etc. limiting compression) Note: chest wall; lung compliances are similar over range of breathing pressures

Note: chest wall wants to spring open; lung wants to collapse Chest wall compliance disorders:

E.g. fibrothorax; scarred, thickened pleura; obesity too (less compliant)

Respiratory System Compliance Compliances are in series so add reciprocals

Makes sense: blowing up a balloon inside of another balloon would be harder than blowing up either one

1/CRS = 1/CL + 1/CCW How does this relate to FRC, RV, TLC, and all that stuff?

See graph – just adding the pressures of CW & lung to get RS

FRC: inward recoil of lungs = outward recoil of relaxed thorax o Graph: chest wall pressure is same distance from zero as lung pressure

RV: all airways are closed

TLC: inward recoil of RS = outward recoil of maximally contracting inspiratory muscles

Air flow dynamics Resistance = pressure / flow

What pressure is needed to generate flow?

↑ with turbulence, tube length, and DECREASING RADIUS

↓ with ↑ lung volume

80% of resistance is in LARGE AIRWAYS (bigger than subsegmental) o Remember, small airways have large total area

Flow patterns

Laminar concentric layers of air flow slipping past each other @ different velocities (faster in middle)

Resistance: independent of gas density

Turbulent molecules tumbling around (still with a net vector in flow direction)

Resistant: strongly dependent on gas density (↑ with ↑ density)

Transitional near bifurcations; areas with eddies partially disrupt laminar flow

5

Reading a CXR Not on the exam; just a few pictures & concepts that seemed helpful

Assessing quality

Not too much lung field above clavicle (bending over?)

Should be able to just make out outlines of vertebrae through mediastinum (exposure good?) Note: left hemidiaphragm “stops” (mediastinum & abdominal contents are same opacity)

Distribution Upper or lower?

Unilateral or bilateral?

Masses (>4cm)?

Nodules (<4cm)? Infiltrates?

Alveolar? Water

Blood

Cells

Pus

Protein

Calcium

Interstitial? Reticular (lines)

Nodular

Combined

Honeycomb

Ground glass

Mixed?

Effusions?

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Pulmonary Function Testing

Spirometry: Inhale to TLC

Exhale as rapidly/completely as you can

Measure exhaled volume vs. time Results:

FEV1 : Volume exhaled in 1st second

FVC: total volume exhaled

FEV1/FVC: fraction of total volume exhaled in 1st second (FEV1%) o Normally ~0.8

Interpretation of Spirometry

Ventilatory defect: FVC FEV1/FVC

Restrictive ↓ Normal or ↑

Obstructive Normal or ↓ ↓

Common Causes Of:

Restriction Obstruction

Small / stiff lungs Small / stiff chest wall

Respiratory muscle weakness

↑ airway resistance

↓ lung recoil Increased airway

closure

Pulmonary fibrosis Kyphoscoliosis ALS Chronic bronchitis Emphysema Asthma

Flow-volume curves Spirograms show expired volume and time; you can also plot flow per time. Either way lets you calculate FEV1 and FVC See chart to left

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Can also have patient inhale as fast as possible at end of spirometry to generate flow-volume loop (see right)

Lesion Affects…

Upper airway obstruction

inspiratory flow > expiratory

COPD expiratory flow > inspiratory

Fixed obstructions (e.g.

tumor around trachea) could affect both

Arterial Blood Gases What can we assess from blood gases? Oxygenation: hypoxia Ventilation: hypo or hyper ventilation Acid/base balance: nephrology

Arterial Oxygenation Remember the oxyhemoglobin saturation curve

Most O2 bound to Hb

Saturation, O2 content change very little above PaO2 = 60mmHg

Mix of blood with high and low PO2: dominated by low value o E.g. mix 95% saturated blood ( 100mmHg) with 75% saturated blood (40 mm Hg) –

end up with 87% saturated blood (average) but because curve is sigmoidal, PO2 is about 55 mm Hg (not an average!)

Clinically significant hypoxemia:

Arterial Hb saturation of less than 90% (PaO2 60 mm hg)

Alveolar gas equation: memorize this: PAO2 = [FIO2 x (PB-47)] – (PaCO2/0.8)

If on room air: simplify it! PAO2 = 150 – PaCO2/0.8 o Room air close to 20% oxygen

Inspired [O2] changed by water vapor & CO2 A-a gradient (i.e. who cares about the alveolar gas equation?)

Calculate PAO2 (alveolar PO2) and compare it to arterial PO2 – are you getting oxygen from alveoli to arteries?

Normal values: < 20 on room air (20% O2) < 100 on 100% O2

Increase: suggests venous admixture (poorly oxygenated blood reaching circulation)

PAO2 Alveolar O2 tension

FIO2 Fraction inspired O2

PB Barometric pressure (corrected for water pressure, - 47)

PaCO2 Arterial CO2

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Causes of Hypoxemia Cause Description A-a Response to

O2

V/Q Mismatch Maldistribution of V relative to Q (ventilation / flow)

Some areas are overventilated (↑ PaO2)

but doesn’t correct for underventilated areas (↓ PaO2) ↑ Corrects

Shunt

Extreme V/Q mismatch

lots of venous blood gets to L heart without traversing ventilated alveoli

E.g. collapsed alveoli, septal defect, etc. –

can be intrapulmonary or

extrapulmonary

↑ Doesn’t correct

Hypoventilation Alveolar O2 diluted by ↑ PACO2

PACO2 MUST be ↑ nl

Good response can ↑ resp

acidosis!

Diffusion impairment

Hypoxia with exercise, not at rest Red cells don’t have time to reach equilibrium on exercise

↑ with exercise

Decreased FIO2 Altitude, for instance nl

Ventilation: PaCO2 & pH

PaCO2 = K x VCO2 / VA (K=0.86; VA = VTidal – VDead Space) VCO2 = CO2 production; VA = alveolar ventilation

Just K x CO2 production / CO2 removal PaCO2 VERY tightly controlled (35-54 mmHg)

>45 =HYPOventilation (VA is ↓: total ventilation ↓ or ↑ dead space)

<35 = HYPERventilation

Terms for actual PaCO2 findings: hyper- & hypocapnia

Hyperbolic relationship between VA and PaCO2 If you’re hypoventilating (low part of curve), can get BIG PaCO2 changes

Exercise (dotted curve): need more VA to maintain PaCO2

pH: Acidosis (<7.35) vs Alkalosis (> 7.45)

Can calculate pH changes for PaCO2 changes (see table to right)

Diffusing Capacity Fick’s law: gas flux = (membrane diffusion coefficient X pressure gradient) / (thickness X area of membrane)

Don’t memorize; just know that those are the things that go into flux

Simplify everything: flux (J) = driving pressure (ΔP) X diffusing capacity (DL)

𝐉 = 𝚫𝐏 × 𝐃𝐋 𝐃𝐋 = 𝐉/𝚫𝐏 To measure diffusing capacity:

Calculating pH changes due to PaCO2 changes

A 1 mmHg ↑ in PaCO2 causes

Acute (non-compensated) ↓ 0.008 in pH

Chronic (compensated) ↓ 0.003 in pH

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Can’t measure DLO2, although we’d like to – backpressure (dissociates from Hb)

Use DLCO instead! Doesn’t have backpressure (binds really tightly to Hb) o Pt inhales 0.3% CO in 10% He (both diluted equally, He is marker), holds breath 10 seconds o Exhaled mixed alveolar gas sampled, exhaled [CO], [He}]measured, o Calculate: how much CO was able to diffuse?

Interpreting DCO

Sensitive, non-specific (something’s wrong, but huge DDx); wide normal range

↓ DCO: ↓ alveolar-capillary SA for gas exchange

↑ DCO: ↑ pulmonary capillary blood volume

Lung Volumes How to measure residual volume?

The rest we can get from spirometry

Need to use GAS DILUTION (He, nitrogen, Ar, methane) Gas dilution

Measures only ventilated lung units Breathe in & out to equilibrate

Calculate measure diluted [He]

Use known initial volumes & initial / final [He] to figure out how much lung capacity was around (TLC), then calculate RV by TLC-VC

Plethysmography (body box) is another option

Uses Boyle’s Law (P1V1=P2V2)

Measures ALL thoracic gas volume (cysts & bullae too)

INTERPRETING LUNG VOLUMES

↓ TLC Restriction

↑ TLC Hyperinflation

↑ RV Air trapping

Key Points Patients can be pathophysiologically categorized with use of:

Spirometry and Flow-volume curves

ABGs

DCO

Lung volumes Patients can be diagnosed with H&P, PFTs, x-rays….

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Interstitial Lung Disease Pathogenesis of restrictive diseases:

Stiff lungs (don’t expand)

Stiff chest wall (or too small)

Respiratory muscle weakness (diaphragm rises small lungs) Interstitial Lung Disease: STIFF LUNGS

150+ clinical entities can cause ILD

“Diffuse parenchymal lung diseases” would be better o Lung is simple

tubes (airways: asthma & COPD are Dz) blood vessels (pulmonary HTN) parenchyma (alveoli) – the stuff that isn’t tubes or vasculature

What is the interstitium?

Potential space with vascular components; substrate for gas exchange

Normally should contain nothing (better for gas diffusion) ILD / Diffuse parenchymal lung diseases (DPLD)

Inflammation and/or fibrotic process affecting pulmonary interstitium

Results in scarring of lung o ↓ lung compliance o ↓ lung volume (FVC, TLC) o ↓ diffusion capacity (DLCO) – lets you distinguish from stiff chest wall or resp mm weakness

CLINICAL CLASSIFICATION OF ILD

Occupational/environmental Pneumoconiosis (aspestos, silicosis)

Toxic inhalation (ammonia, sulfur dioxide)

Hypersensitivity pneumonitis (farmer’s lung, pigeon-breeder’s lung)

Connective tissue disorders Pretty much any autoimmune disease (scleroderma, RA, SLE, polymyositis-dermatomyositis, etc)

Drug / treatment-induced dz Amiodarone, cancer drugs (bleomycin, methotrexate), radiation therapy

Idiopathic disorders Idiopathic pulmonary fibrosis

Sarcoidosis Bronchiolitis obliterans organizing pneumonia (BOOP), Eosinophilic granuloma

Hereditary / genetic Various mutations: surfactant proteins B/C, ABCA transporters, telomerase mutations, Hermansky-Pudlak syndrome (all Hopkins-discovered)

“Other” disorders Lymphangitic carcinomatosis, respiratory bronchiolitis, tuberous sclerosis / lymphangiolyomatosis (LAM), systemic lipoidosis

Now, on to some specific examples

Idiopathic Pulmonary Fibrosis Epidemiology: 25-30% of all cases of interstitial disease; 8-12/10k and rising, males>females (2:1), mean age 65

Think older males; significant morbidity & mortality (≈ breast cancer)

Distinct disease entity: not just waste basket term Presentation: Progressive dyspnea on exertion for one year or more

ILD: A restrictive disorder

↓ TLC (by def’n)

↓ FVC (almost always)

Normal FEV1/FVC (no flow restriction)

↓ DLCO (specific to stiff lung restrictive dz)

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CXR:

↑ interstitial markings

Fibrosis

Predominantly LOWER LOBE involvement & SUBPLEURAL

CT:

Architectural distortion o (traction bronchiectasis: bronchi

pulled apart by stiffness)

Honeycombing is diagnostic (radiographic hallmark of IPF) o Don’t need biopsy anymore!

Pathogenesis: Initiating event unknown (idiopathic!)

Inflammatory response, epithelial cell injury, neovascularization, repair / fibrosis all seen on path

Genetics (telomerase defects / telomere shortening may be involved; maybe why ↑ in older people?)

Pneumoconiosis Accumulation of dust in the lungs; results in tissue reaction

Reaction can be collagenous or non-collagenous

Excludes dust exposure that results in: o malignancy, asthma, bronchitis, or emphysema

Silicosis Most prevalent chronic occupational lung dz in the world!

Inhalation of silica, usually in quartz form

Settings (esp. if not using appropriate respiratory protection) o Mining (hard rock/ anthracite coal), foundries, brickyards, glass/ceramic

manufacturing, industrial sandblasting

Clinical Presentation: Dyspnea & cough (>20yrs low-moderate exposure, 5-10yrs high-level exposure)

CXR:

Small rounded opacities in upper lung zones Conglomerate (>10mm) opacities

o Called progressive massive fibrosis (PMF) o Looks like tumor o Small opacities can progress to PMF

PFTs : identical to IPF

May see airflow obstruction, ↓ FEV1/FVC occasionally Pathogenesis:

1. Silica particles deposit in alveoli 2. Mϕ gobble them up 3. Mϕ injured / cell death happens 4. Release of intracellular proteolytic enzymes lung injury / fibrosis 5. Silicotic nodules form!

Types of Pneumoconiosis

Silicosis

Asbestosis

Coal workers’ pneumoconiosis

Talcosis

Berylliosis

Hard-metal pneumoconiosis o Tungsten carbide o Cobalt dust

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Diagnosis of Interstitial Lung Disease Patient history is crucial!

o Check for exposures, how long have Sx been going on, any Hx autoimmune dz, other sx?

Chest radiograph useful (& chest CT)

Fiberoptic bronchoscopy o Broncheoalveolar lavage: rule out infection, look for eosinophils o Transbronchial biopsy: e.g. for sarcoidosis

Thorascopic / open lung biopsy too

Treatment of Interstitial Lung Disease Note: no FDA approved therapies for IPF: for a disease that affects 1/2M people in US & causes 40k deaths / year! In general, for ILD: (* = not of benefit for IPF)

Avoid exposure to causative agent

Corticosteroids*

Alternative immunosuppressive agents* o Cyclophosphamide o Azathioprine

Anti-fibrotic drugs*

Follow pt response to therapy with serial PFTs & pt-reported Sx o How are they doing? Try something new if not working

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COPD COPD: chronic disease characterized by REDUCED EXPIRATORY AIRFLOW Diseases included in COPD: both caused by cigarette smoking

Emphysema

Chronic bronchitis Others: asthma /

asthmatic bronchitis / bronchiectasis / CF technically COPD too, but not in common parlance

Emphysema Chronic Bronchitis Asthma (for comparison) Anatomic definition (need Bx to Dx) Historical definition (Dx via phone!) Definition:

Progressive destruction of alveolar septa & capillaries

Airspace enlargement & bullae development

Destruction of septa ↓ elastic recoil (↑ compliance)

↓ maximum expiratory airflow

↑ static lung volumes

Definition: chronic mucus hypersecretion

> 3mo chronic sputum production for 2 consecutive years

↑ airway resistance ↓maximum expiratory airflow

Episodic cough, wheezing, dyspnea Often considered pathophysiologically separate from COPD unless chronic abnormalities present:

Lung function

Cough

Sputum (“asthmatic bronchitis”)

Natural History of COPD FEV1 normally ↓ with age; much faster in COPD COPD:

Usually clinically recognized in older pt / 50s (Sx)

Changes start much earlier (can detect with PFTs!) o Just need spirometry (cheap!) to see FEV1

Only 1 in 7 smokers get COPD

But in those who are going to get it, these changes start early

If you quit:

Rate of FEV1 drop goes back to normal! Delay onset of Sx

COPD: Clinical Course

Progressive ↓ in pulmonary function

Punctuated by acute exacerbations

Eventually: disability & premature death

Risk factors for COPD

CIGARETTE SMOKING Older age

Male gender (?)

Airway hyperreactivity

Low socioeconomic status

Alpha-1 anti-trypsin deficiency

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Pan-Acinar vs Centrilobular Emphysema Remember: acini / lobules are the functional unit surrounding one respiratory bronchiole

Affects Part of Lung Cause Picture

Pan-Acinar Entire acinus

Base > apex

Alpha-1 antitrypsin deficiency

Centrilobular Respiratory bronchiole

Apex > base

Cigarette smoking

Protease Imbalance Theory of Emphysema Basic idea: ↑ proteases & ↓ antiproteases imbalance damage

Mϕ secreting cytokines in middle of everything

Cytokines hyperplasia of other cells (e.g. mucus cells) o Can lead to bronchitis too!

Evidence: Alpha-1 antitrypsin (normally inactivates proteases) deficiency leads to

premature emphysema

Proteases such as elastase causes severe emphysema in lab animals

Cigarette smoking causes inflammatory cells to secrete proteases (which accumulate in the terminal airspaces)

Cigarette smoke inactivates anti-proteases

Pink Puffers & Blue Bloaters (typical COPD pt has elements of both) Findings Picture

Pink Puffer

Emphysematous

Hyperinflated

Thin physique

Dyspneic

Low PaCO2

Worse O2sat w/exercise

Purses lips

Shoulders elevated

Leans forward

Accessory mm to breathe

Blue Bloater

Bronchitic

Less hyperinflated

Obese physique

Not dyspneic

High PaCO2

Better O2sat w/ exercise

Cyanotic

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Pathophysiologic Abnormalities in COPD Probably good to memorize these lists of 3 things Airflow Obstruction: causes

1. ↓ elastic recoil (emphysema) 2. ↑ airway resistance (chronic bronchitis) 3. ↑ airway smooth muscle tone (asthmatic bronchitis)

Hypoxemia: causes

1. V/Q mismatch (because of non-linear Hb dissociation curve) 2. Hypoventilation (late in course; more common in chronic bronchitic) 3. Diffusion impairment (exercise or high altitude;

more common in emphysema) Flow-volume loop:

More curvilinear (some areas emptying very slowly – bullae, etc)

Smaller in general (less volume) Air trapping & hyperinflation

Air trapping makes RV↑ (extra volume that can’t be expelled)

Hyperinflation means TLC↑ (bigger overall volumes) Operating lung volumes (rest vs. exercise)

Normally ↑ VT by blowing out more during exercise

In COPD: o can’t blow out fast enough o take another breath before fully exhaled o ↑ end expiratory volume o VT ↑ to keep up with metabolic demands o Reach TLC – need to stop exercise

(can’t ↑ VT any more)

CXR findings (not good for screening vs. spirogram)

↑ A-P diameter

Flat diaphragms (less efficient) ↓ vascular markings

↑ size of central pulmonary arteries

↑ anterior air space ↑ sterno-phrenic angle

CT findings with density masking:

better for Dx

Too much air (↓ density)

Pulmonary Hypertension: due to chronic alveolar hypoxia

Give O2 to prevent

Maybe contribution from destruction of pulmonary capillary bed too

Major pathophysiologic abnormalities in COPD 1. Airflow obstruction (Early) 2. Hypoxemia (Mid-course) 3. Pulmonary HTN (Late)

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Gas exchange: problems progress over course of disease Consequences of pulmonary HTN

RV dilatation

↑ venous pressure (↑ RA pressure too) o Peripheral edema o Can’t ↑ CO with exercise or stress

Decreased survival

50% 5-year mortality with cor pulmonale (RH failure)

Treatment of COPD Chronic oxygen improves survival in pts with hypoxemia

Concentrator or liquid O2

deliver with nasal cannula, Venturi mask (control concentration), or transtracheal catheter (high flow) as needed

Smoking cessation slows progression

ASK ABOUT SMOKING & give forceful encouragement to quit (↑ quit rate 50%) Encourage unambiguous quit date

Follow up progress

Nicotine replacement (transdermal patch, gum, lozenge, spray)

Bupropion or varenicline

Refer to group program

1-800-QUIT-NOW – have somebody else do the counseling for you! Long-acting bronchodilators & inhaled corticosteroids

↓ exacerbations & ↑ survival Influenza vaccination & pneumococcal vaccination might have benefit too?

Advanced treatment:

Lung transplant

Alpha-1 antitrypsin replacement therapy ($30K/yr, not known if benefit, only for pan-acinar)

Lung volume reduction surgery

Long-term mechanical ventilation

Exacerbations in COPD Increase in cough, phlegm, dyspnea

Occur on average 2-3/year

50-75% caused by bacterial infection

Treated with antibiotics, steroids

Impair quality of life

May result in acute respiratory failure

Can be prevented by inhaled bronchodilators, inhaled steroids

Treatment for Acute Respiratory Failure Non-invasive positive pressure ventilation

Intubation & mechanical vent if needed

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Pathophysiology of Asthma

Definition: Chronic lung disease characterized by 1. Chronic airway inflammation 2. Airway hyperresponsiveness 3. Variability in outflow obstruction

Cause: UNKNOWN

Genetic factors (clusters in families, ↑ in atopic pts - ↑ ability to generate IgE after allergen exposure)

Environmental exposures (tobacco smoke, occupational agents, air pollutants)

Respiratory infections? Controversial: exacerbates but no good data for causation

Chronic Airway Inflammation Triggers: lots!

Cockroaches, mice, irritants, infections, etc. (more later)

Effectors

EOSINOPHILS major player

Mast cells (IgE) too Histamine, prostaglandins, etc. released

Leads to:

Bronchoconstriction

Airway edema

Goblet cell hyperplasia (↑ mucus) Eventually results in ↑ AIRWAY RESISTANCE and AIRFLOW OBSTRUCTION (wheezing, shortness of breath)

Airway Hyperresponsiveness Exaggerated bronchoconstriction after environmental exposures or response to stimuli

We all do it; just more in asthma pts

Allergens (e.g. dust mite), irritants (e.g. tobacco smoke), methacholine (diagnostic) Mechanism unclear: airway inflammation? Abnormal neural control of airways? ↓ ability to relax smooth mm?

Methacholine (MCh) challenge

MCh: cholinergic agonist bronchoconstriction

Inhale progressively higher [MCh] & record FEV1 after each dose o Precipitous drop in asthma pts

Provocative Dose 20 (PD20): dose needed to provoke 20% fall in FEV1 o PD20 < 8 in asthma

NOT PREDICTIVE of sx severity

Sensitive but NOT SPECIFIC: all pts with low PD20 don’t have asthma o COPD, CF, other resp disorders o 10-15% normal pts o Can’t use by itself to Dx asthma

Epidemiology

20M (7%) in US

M>F in kids; F>M in adults

Most common childhood chronic dz

Prevalence, mortality rate ↑

↑ mortality in AA pts (big gap!)

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Variability in Airflow Obstruction Obstructive ventilatory defect present

LOW FEV1/FVC RATIO (<0.7) Can at least partially reverse with bronchodilator therapy

Usually FEV1 ↑ >12%, 200mL Obstruction VARIES TEMPORALLY: within and between days

Often worse in early AM

Symptoms are episodic o DYSPNEA o CHEST TIGHTNESS o WHEEZING o COUGH (can be only

presenting symptom!)

Can see fluctuation in FEV1 with time Obstruction VARIES SPATIALLY as well

Radiolabeled aerosol deposits: patchy deposition mostly in large & proximal airways; some airways less obstructed

Asthma Exacerbations Acute ↑ in airway resistance from: bronchoconstriction, airway edema, mucus / cell debris

Usually over days-weeks but can be sudden

60% asthmatics: 1+ severe exacerbation/yr Clinical Presentation Hx: ↑ SOB, chest tightness, wheezing, cough PE: tachypnea, wheezing, prolonged expiration Radiology: hyperinflated, flattened diaphragms Physiological alterations in exacerbation: Hyperinflation:

Diaphragms flattened mechanical disadvantage (hard to flatten more to breathe!)

↑ work breathing o abdominal paradox: use less efficient intercostals to breathe, so abdomen goes in instead of out on inspiration o Can lead to respiratory failure

Pulmonary HTN: alveolar capillaries compressed (↑ alveolar pressure)

Signs of a severe asthma exacerbation 1. Pulsus paradoxus: > 10 mmHg drop in SBP with inspiration, caused by ↑ pleural pressure swings (↓ LH filling)

2. Respiratory muscle fatigue: from being hyperinflated

o Can’t speak in full sentences o Accessory mm of respiration (sternocleidomastoid, intracostals) retracting o Paradoxical abdominal movement (abdomen in instead of out on inspiration)

Triggers VIRAL INFECTIONS (most common cause; rhinovirus, influenza)

Inhaled irritants (cig smoke, ozone, particulates) Inhaled allergens (dust mites, animal dander – cats, mice, etc)

Exercise or cold air (irritates!)

Occupational exposures Specific to patient (need to test & find out). Can have delayed symptoms too – exposure, get Sx hours later!

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3. Hypercarbic Respiratory Failure (↑ PaCO2) o Diaphragm fatigued (↑ work of breathing) alveolar hypoventilation with ↑ PaCO2 o Normally asthma pts hyperventilate during exacerbation so PaCO2 should be low (<40mmHg)

o A NORMAL PaCO2 is therefore a bad sign in asthma exacerbation

Treatment of Asthma Patient education: what it is, how to manage, what drugs are, etc. Avoid triggers: needs to be comprehensive

Smoke avoidance, Pet avoidance, Roach control, Mouse control

Dust mite modifications: o Allergy proof covers, Wash linens in hot water weekly o Vacuum/sweep weekly, Carpet/curtain removal, Humidity control

Asthma management plan

Can have pt measure peak expiratory flow rates at home

Plan with pt: what actions to take based on peak flow Helps with appropriate medication use (not overuse), can have pt call &

schedule appt or prescription refill if drastic decline, etc.

Pharmacologic treatment:

1. Bronchodilators: relax bronchial smooth muscle a. Short & long-acting β2 agonists, anticholinergic meds b. Inhaled c. Short-acting meds for RESCUE ONLY

2. Inhaled corticosteroids: anti-inflammatory a. Cornerstone of daily control therapy b. Add if pt needs their bronchodilator

>2x/wk, for instance

3. Oral corticosteroids a. If can’t control with inhaled meds b. ↑ side effects

4. Others: if refractory to tx Drug Description

Cromolyn sodium / nedocromil Anti-inflammatory, Mast cell stabilizer (↓ degranulation)

Leukotrine modifiers Anti-inflammatory, less effective than corticosteroids (can use if mild asthma or corticosteroids contraindicated)

Theophylline Methylxanthine bronchodilator Anti-IgE Really expensive; IV; only in very severe cases

Acute Exacerbations:

↑ frequency of short-acting bronchodilators with ↑ Sx

Often needs oral corticosteroids, may need subQ or parenteral β-agonists if severe

Monitor for respiratory failure Inhaled drug delivery:

Metered-Dose Inhalers (MDI) Aerosolized spray with a propellant, currently with hydrofluoroalkane

Requires slow deep inhalation with 10 sec breathhold to be most effective

Spacers with MDIs Minimizes oropharyngeal deposition with MDI

Requires less coordination

Can deliver drug as effectively as with nebulizer, even during exacerbation

Dry-powder Inhalers Rapid inhalation

Dose lost if exhales into the device

Nebulized Solutions Expensive

Depends less on patient coordination

Goals of treatment

1. Control symptoms 2. Prevent exacerbation 3. Maintain lung function as close to

normal as possible • Use objective measures: pt

may not realize how bad it is!

4. Avoid adverse effects from medications

5. Prevent irreversible airway obstruction

• Is asthma predisposition for COPD?

6. Prevent asthma mortality

20

How to use MDIs & Spacers MDI: don’t put it the whole way into mouth (just coat back of throat!) Spacer: discharge before inspiration (MDI alone – simultaneous)

Step Care Sx, severity depend on:

frequency of exacerbations

frequency of nocturnal symptoms

variability in lung function (FEV1 / PEFR) Step up if: frequent need for β-agonist Step down (remove treatments) if 1-6mo symptom control

Summary (from slides)

1. Asthma is more common in children (↑ mortality in African-Americans) 2. Three cardinal features: airway inflammation, airway hyperresponsiveness, variable airflow obstruction 3. Genetics, respiratory infections, and environmental exposures all likely contribute to developing asthma 4. Asthma Sx: wheeze, dyspnea, cough, chest tightness 5. Bacterial infections rarely trigger asthma exacerbations 6. Airway hyperresponsiveness (positive methacholine challenge) is not specific for asthma 7. Airflow obstruction is due to bronchoconstriction, airway edema, and inflammatory exudates in airway lumen 8. Pulsus paradoxus, a rising PaCO2, and respiratory muscle fatigue indicate a severe asthma exacerbation 9. Treatment should include patient education, environmental control practices, an asthma management plan

and medications based upon symptom severity.

21

Expiratory Flow Limitation Expiratory Flow Limitation (defn): ↑effort to exhale does NOT cause ↑ expiratory flow rate

A spirogram (left) is any graph of exhaled volume vs time. The slope is the expiratory flow (volume per time); can be graphed against total exhaled volume (right) as expiratory flow – volume relationship The pleural pressure generated is analogous to the effort exerted.

↑ effort ↑ expiratory flow: but only to a point. The curves all superimpose on their way back down

Isovolume effort-flow relationship:

At a given volume, there’s a relationship between % max effort and flow

↑ max flow at ↑ volume still in lung (earlier, before you’ve exhaled the volume) – e.g. A vs B

Flow restriction: there’s a point of effort at which ↑effort doesn’t translate to ↑flow

o Normally about 60% max effort is where flow restriction happens

What Causes Flow Limitation? For the following, pretend that this is all isovolume (lung volume constant despite expiratory effort & airflow)

Picture What’s going on

Ppl is about -8 if you hold your breath with glottis open after inspiration

That makes Pel (elastic recoil) 8 (positive = lung wants to recoil)

PATHOPHYSIOLOGY OF RESPIRATORY FUNCTION: BASIC CATEGORIES Restrictive ventilatory defects Difficulty getting air into the lungs Obstructive ventilatory defects Difficulty getting air out of the lungs

Gas exchange defects Difficulty with efficient movement of gases between alveoli & blood

22

Expiratory muscles contract

Isovolumic so Pel has to be the same (8)

↑Ppl (contraction of expiratory muscles), so ↑Palv too (keep Pel same)

↑Palv now creates a gradient, and ↑airflow out At the same time, Ppl pushes in on bronchus, causing it to narrow

esp. distal bronchus – where pressure is lower (gradient with Patm=0)

↑resistance so ↓airflow out

Flow limitation:

airflow stops increasing at some point (60% max effort in normal)

resistance from ↑ Ppl cancels out ↑ airflow from ↑ Palv But if totally occluded, ↑ pressure inside bronchus (>Ppl)

forces airway open again

Airway opens up again now the pressure is greater outside (forces closed) Paradox: if closed, pops open; if open, forced closed Resolved by either:

Bronchus fluttering open & closed

Bronchus doesn’t really close; self-adjusts diameter to maintain it just open enough to balance opening & closing

What determines max expiratory airflow? Determinant Contributing factors Picture

1. Airway resistance (bronchi)

Diameter

Length

2. Tendency of airway to

close (or resist closure)

Bronchi have cartilage, smooth mm to resist closure, but will still shut if pressure across them is more than slightly negative

Smooth muscle tone (↑ with asthma so ↑closure)

Mucosal thickness

Tethering effect of parenchyma

3. Elastic recoil of lung

Lung volume (↑volume ↑ recoil)

Elastic properties of lung tissue

Emphysema: ↓elasticity, ↓ elastic recoil ↓ flow at any

volume. Opposite for IPF (↑elasticity ↑elastic recoil ↑ flow at any volume)

23

Why is this a problem in chronic obstructive lung disease? Normally: lots of reserve at rest

Exhalation happens far underneath maximal envelope COPD: reserve lost

↓ volumes, ↓ maximal expiratory flow

Even at rest, operating on your maximal envelope

Try to exert can’t ↑ expiratory flow

What does this have to do with other systems? Bladder like lung, urethra like bronchus

↑ abdominal pressure to try to force urine out (like ↑ pleural pressure)

Prostate squeezes urethra like pleural pressure on bronchus o ↓ flow with prostatic hypertrophy

Flow limitation happens during micturition – can’t get it out! Similar Flow Limitation in:

Expiratory airflow

Inspiratory airflow

Vena cava blood flow

Micturition

Blood flow during CPR

24

Pulmonary Vascular Disease

Review from last year: pulmonary circulation Key points about the pulmonary circulation:

Entire cardiac output goes through it

Low pressure drop (25-5)

Low resistance (low pressure drop!)

PVR =PPA− PLA

𝑸𝒕

o Resistance = pressure gradient over flow. o Pressure gradient (pulmonary artery to LA) divided by the flow

(cardiac output = venous return)

Passive: Pulmonary circulation not a rigid tube:

↓ PVR with ↑ CO (passively!)

Capillaries are recruitable & distensible No active processes needed

Maintains pressure gradient over CO range

Active: Vascular tone can be modified to adapt to changing Qt (=CO)

Change along curve = passive adaptations

Shifting between parallel curves = vasoconstriction or vasodilation

PVR is U-shaped curve (passive mechanisms)

LOWEST PVR at FRC o ↑ lung volume: compress alveolar vessels (↑ PVR) o ↓ lung volume: compress extra-alveolar vessels (↓ PVR)

Hyperinflation (e.g. asthma): ↑ PVR (above normal FRC)

ARDS: lowers FRC (↑ PVR too)

Pulmonary Hypertension: Definition Abnormal elevation of pulmonary artery pressure, the gradient between pulmonary artery & pulmonary vein, or increase in PVR

Causes of Pulmonary Hypertension

Remember R=ΔP/Q, so PVR =PPA− PLA

𝑸𝒕

Rearranging to find things that can affect PPA:

PPA = Cardiac Output × Resistancedownstream + PLA So ↑ PPA with

1. ↑ left atrial pressure 2. ↑ downstream resistance 3. ↑ cardiac output

Definition: MEMORIZE THIS

Mean Ppa > 25 mm Hg Can be measured non-invasively with electrocardiography

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1. ↑ LA pressure

LV or mitral valve disease (cardiomyopathy, mitral regurgitation or stenosis, etc) ↑ LA pressure ↑ backpressure so ↑ pulmonary arterial pressure Most common cause of pulmonary hypertension (because LH dz very common) Treatment: unload left heart (treat underlying condition to ↓ LA pressure)

2. ↑ downstream resistance Very uncommon to raise resistance in veins – usually arteriolar or arterial

↑ arteriolar resistance: primarily hypoxic Hypoxia causes ACTIVE pulmonary arteriolar vasoconstriction

(↑ resistance) o Altitude, hypoventilation, etc. o Why? Hypoxic Pulmonary Vasoconstriction to match V/Q o shut down blood flow to underventilated lobe; reduce shunt

o Good locally but bad globally (leads to pulmonary HTN) o Mechanism: maybe from inhibition of K

+ channels (see K

+ channels shut down

in hypoxic PA cells but not endothelial cells from other areas of the body – would want to vasodilate there!)

COPD: both hypoxia & distortion of alveoli & capillaries

Interstitial disease: sarcoid, IPF, etc o distorting capillaries mechanically, some dropping out

ARDS, positive pressure ventilation, others

↑ arterial resistance: primarily vascular

Looking at more central, larger arteries

Pulmonary Arterial Hypertension o Idiopathic, Familial, or associated with CVD / HIV /

Liver disease /Drugs

Chronic thromboembolic disease o Needs to be chronic o throwing lots of clots, ↑ resistance over time

(occluding vessels downstream)

3. ↑ cardiac output ↑ pulmonary blood flow ↑ PPA

o Anemia, hyperthyroidism (↑ CO); generally not severe; reversible

Chronic ↑ flow vascular remodeling ↑ resistance (more fixed form) o L-to-R shunt (ASD/VSD), Sickle cell anemia too

IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION (PRIMARY PULMONARY HYPERTENSION)

Women 20-45 yo

Dyspnea >1 yr

PPA markedly elevated at dx

Median survival = 3 yrs (before Tx)

TGF-β involved in vascular remodeling (definitely in familial forms, probably in

sporadic form too) No cause or association identifiable

o Rule out other causes

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Consequences of pulmonary HTN ACUTE (e.g. Acute PE) CHRONIC (e.g. chronic lung dz, PAH)

RV not hypertrophied; fails quickly (pushing against ↑ resistance)

RA pressure ↑ as RV fails

↑ catecholamines to ↑ mean systemic pressure, ↑ HR

↓ Venous return / CO shock, sudden death

Acute PEs have 10-15% mortality

RH has time to hypertrophy o See BIG RV and RA

RA pressure ↑ over time (can’t eject everything) pulmonary hypertension

Venous return, CO maintained (↑ sympathetics, ↑ mean systemic pressure to augment return)

Cor pulmonale: RH failure due to pulmonary disease

These are patients with COPD or CHRONIC HYPOXIA, for instance

RH has to keep pushing against diseased lung, eventually fails

Findings: Edema, ↑JVP, loud P2, right S3, RV heave, tricuspid regurg, hepatic congestion, big pulmonary arteries, ↓DLCO Dx with echocardiogram or right heart cath

Prognosis:

Correlates with mean pulmonary arterial pressure! o See graph: ↑ PPA = ↑ mortality

Similarly: o ↑ RA pressure (RH failing!) = 3 mo median survival o ↓ CO (failing) = bad prognosis o Hyponatremia (compensatory mechanisms failing) = bad prognosis

Treatment of pulmonary HTN Goals of treatment:

UNLOAD the RV o Vasodilation

Reverse hypoxia & active vasoconstriction O2 is a vasodilator!

Reverse remodeling

Avoid in situ thrombosis & embolism from deep veins (anticoagulants)

VASCULAR MODIFIERS Prostaglandin I2 (prostacyclin)

Endothelin receptor antagonists

(e.g. Bosentan) PDE5 inhibition

(e.g. sildenafil / Viagra®)

Vasodilation & inhibition of remodeling

Requires chronic perfusion but improvement in survival (50% at 5yrs vs 20% w/o Tx)

Endothelin usually leads to vasoconstriction, proliferation, migration of smooth mm (reverse!)

Can give orally; good functional data (six minute walk) but not good data for survival (should correlate?)

↑ cGMP vasodilation, inhibition of remodeling

Can give orally, again good functional data but not good data for survival

Lung transplant: cures PAH but has significant problems in its own right

5yr survival is ~50% (worst of transplants)

Summary: Pulmonary hypertension can arise via various physiologic or pathophysiologic mechanisms (most still unclear)

Harder to diagnose than systemic HTN / often presents late

Major clinical importance of pulmonary HTN: effect on the RV (acute vs. chronic)

Strategies to decrease PVR and unload the RV have beneficial effects on patients with pulmonary hypertension

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Obesity & Breathing Disorders Obesity: BMI kg/m2; >25 overwt, >30 obese. Growing problem (ha!). More obesity in Missisippi.

(mentally recreate obesity epidemic maps) Obesity can cause a range of breathing disorders

Some while awake, some while asleep

Various clinical significances

Sleep apnea Clinical Features

Upper Airway Obstruction

Snoring

Choking, gasping

Alterations during sleep

Excessive movements

Insomnia

Alterations in daytime function

Excessive hypersomnolence

Intellectual deterioration

Fatigue

Cardiopulmonary dysfunction

Hypertension

Glucose Intolerance

MI / Heart Failure / Arrhythmias

Cor Pulmonale

What do you see on overnight sleep study?

1. Periods of no ventilation 2. ↓ O2sat as a result 3. ↑ esophageal pressure variations

(trying to inspire: asphyxic response) 4. Microarousals: waking up from sleep (although not

the whole way – patient doesn’t fully awaken) Interruptions in sleep Daytime hypersomnolence, etc. Epidemiology: measure apnea / hypopnea index (AHI)

# of episodes per hour (<5/night is normal)

<10% in general pop, but ↑↑ in obese men, snorers

Sleep Apnea: Pharyngeal Obstruction Pharyngeal obstruction is key component (critical pressure)

Normally, negative pharyngeal pressure keeps airway open

Apneic patient: throat closes! Positive critical pressure Spectrum of critical pressures: more negative keeps things open

Snoring, obstructive hypopnea can result even at - pressures (more closed)

Positive critical pressure: sleep apnea (totally obstructing)

Obstructive ↓ Sleep Apnea↓

1 2

3

4

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Neuromuscular activity:

Normally, when upright, genioglossus contracts (to pull tongue forward on inspiration to open airway)

Normally, when supine, have more genioglossus activity (tonic activity too to keep tongue out of the way)

Apneic patients have ↓ / absent genioglossal nerve firing

In adults: combination of

structural problems and

this neuromuscular dysfunction Obesity:

More common in upper body obesity (“apples” – mostly males) o Fat encroaching on neck / pharyngeal tissues ↑ collapsibility o Fat ↑ load on resp system / impedes gas exchange o Fat cytokines / humoral factors that ↓ CNS reflexes to keep things open

Therapy for Obstructive Sleep Apnea Change either the nasal or critical pressure ↑ Nasal Pressure: CPAP ↓ Critical pressure:

weight loss

structural approaches

↑ neuromuscular activity CPAP: change nasal pressure

continuous positive airway pressure How it works: wear mask, force air in through nose, inflates throat,

push airway open

Mainstay of treatment

Sleep study: AE = ↑ CPAP pressures o smaller esophageal pressure swings (not trying to breathe

as hard); no obstruction, airflow normal

o Arrows: inspiratory airflow limitation (snoring) Partial obstruction so limit flow at a point

Linear relationship between airway pressure & flow o Below Pcrit, still obstructed o Find point where flow is normal & prescribe CPAP at / above that pressure

Changing Critical Pressure

1. Weight loss (good way, even small reductions help) 2. Structural approach

a. Body positioning b. Uvulopalatopharyngoplasty (surgical – open things up) c. Hyoid / mandibular repositioning (not done much anymore)

3. Increase neuromuscular activity a. protriptyline (not great results) or direct electrical hypoglossal stimulation (experimental)

4. Bypass obstruction (tracheostomy) if really severe

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Daytime Respiratory Complications of Severe Obesity Hypoxemia & hypercapnia cor pulmonale

Hypoxemia: from mechanical alterations

↓ TLC & ↓ FRC (↓ chest wall compliance)

↓ FRC ↓ oxygenation (breathing at lower lung volume) o Below closing volume (where airway closure starts):

some of your airways are going to be closed o Microatelectasis too (small areas of collapse; worsens shunt)

o V/Q mismatch & hypoxemia can result o

Hypercapnia:

↑ metabolic demand (more CO2 produced) if obese

Should ↑ alveolar ventilation (VA) to compensate o Blow off extra CO2

If ventilatory drive depressed, ↑↑PaCO2 (not getting rid of the extra you’re producing)

Why hypoventilation? (see hypercapnia above)

Won’t breathe (CNS problems) o Impaired ventilatory drive, metabolic alkalosis,

CNS-depressing meds

Can’t breathe (mechanical problems) o Neuromuscular disorders, restrictive chest abnormalities (OBESITY),

parenchymal lung dz, upper airway obstruction

In obesity: alterations in drive to breathe

Blunted ventilatory response to CO2 challenge

Leptin deficiency blunts response in mice in and of itself (ob/ob mice) – restored with giving leptin

Therapy for Hypoventilation in Obesity Treat Hypoxemia!

↓ PaCO2 o ↑ VA (alveolar ventilation): blow off more CO2

Stimulant (progesterone) ↑ VA (the same way ↑ metabolic demands dealt with in pregnancy) Mechanical ventilation / CPAP to ↑ VA if needed

o ↓ VCO2 (produce less carbon dioxide!) WEIGHT LOSS (even moderate loss ~ 5% helps!)

Maintain oxygenation o ↑ PIO2 (supplemental oxygen) o Treat sleep apnea (repeated ↓ in oxygen sat)

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Ventilatory Failure Lung failure Pump failure

Primary feature Hypoxia Hypercarbia

Clinical syndromes

Pneumonia, interstitial lung disease,

PE, ARDS

Asthma, COPD, myopathies, neuropathies,

spinal cord lesions

Note: hypercarbia is LATE in pump failure: don’t miss stuff that comes before!

Muscles of Respiration: Review Fiber types & fatigue

Tendency to fatigue related to oxidative capacity Type Oxidative capacity Fatigue Strength

I Slow (S) High Slowly Low IIa Fast-fatigue-resistant (FR) Medium Moderate Medium IIb Fast-fatigable (FF) Glycolic Quickly High

Diaphragm: usually mostly slow & fatigue resistant

As ↑ ventilatory demand: recruits more strong fast-fatigable fibers The Diaphragm: “C-3/4/5 keeps the diaphragm alive!”

Vertical fibers (contract = pull down) o Curvature is mostly the central tendon o Costal and pleural attachments

Actions: o Piston-like: pull down, ↓ pleural pressure (upper ribs sucked in) o Appositional: ↑ abdominal pressure (lower ribs pushed out)

What passes through diaphragm where? o “I ate ten eggs at twelve” = I 8 (IVC @ C8) 10 Egs (esophagus @ C 10) AT 12 (azygous & thoracic duct @C12)

Intercostal muscles & scalene

Really active with every breath (not just accessory muscles)

External = inspiration; Internal = expiration (backwards) Accessory muscles:

Inactive in relaxed breathing; active during exercise or disease

Sternocleidomastoid is big one Pectoralis major / minor, trapezius, serratus anterior too

Expiratory muscles

Remember that TIDAL EXPIRATION is PASSIVE o Use active expiration during exercise, obstruction, dyspnea, pulmonary function testing

Abdominal muscles & internal intercostals

Essential for STRONG COUGH (clear mucus!)

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Mechanisms of Respiratory Muscle Failure

IMBALANCE between DEMAND and CAPACITY ↑ demand, ↓ capacity, or both

RM demand: how much are you breathing and how hard is it to breathe?

↑ demand with … Because…

Minute ventilation

↑ CO2 production Need to get rid of CO2 (e.g. obesity)

↑ Dead space Alveolar ventilation is needed to get rid of CO2: ↑ total ventilation if ↑ dead space to preserve VA

↑ respiratory drive By definition

Respiratory system mechanics

↓ lung compliance Harder to breathe if stiffer

↓ chest wall compliance

↑ airway resistance Pushing against more

RM Capacity: what determines it?

Intrinsic muscle function

Neural function

Lung volume o Remember: muscles have maximum in the tension-length relationship o At point of ideal actin/myosin overlap (length), can get most force

generated (tension)

o FRC: muscles are at length to generate maximum tension

Metabolic substrate: Oxygen supply & blood supply to resp mm

When things go wrong: Hyerinflation Hyperinflation:

Diaphragm “piston” descended, fibers oriented more medially o flattened so away from maximum on length-tension curve

↓ zone of apposition (less effectively turning ribs outward)

Ribs more horizontal (intercostals, scalene less effective)

↓ outward recoil of chest wall (harder to inspire) Results of hyperinflation: ↑ work of breathing

Compliance ↓: at a higher volume so lung is less compliant o For the same VT, you now need to generate a bigger ΔPPL

Intrinsic (auto) PEEP: need to isovolumetrically contract t o get pressure down to zero before next breath!

When things go wrong: COPD RM demand ↑↑ (RM pressure output ↑↑ 3x normal)

Hyperinflated, ↑ resistance, ↑ resting ventilation (↑ dead space)

In COPD, O2 consumption shoots up with ↑ ventilation much faster than in normal subjects RM capacity ↓↓

Hyperinflation (worse with exercise)

Malnutrition (esp. protein) ↓ diaphragm mass

Steroids (COPD Tx) chronic myopathy

Myopathy ↓ oxidative capacity

FRC

END RESULT IN COPD ↑ demand + ↓ capacity = failure

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When things go wrong: Critical Illness Cardiogenic or septic shock: ↓ cardiac output

Hypoxia (because ↓ CO) o ↓ delivery & ↑ demand (↑ ventilation because hypoxic!)

People in shock die when they STOP BREATHING (hypoxia arrhythmias)

Faster progression to lactic acidosis if have to use muscles to breathe

Expt: dogs with blood loss on vent or breathing on own

Use mechanical ventilation if patient in shock even if nothing wrong with lungs Recovery phase (problems after critical illness)

Critical illness polyneuropathy Critical illness myopathy

MOF after sepsis

Demylenation or axonal degeneration After corticosteroids or neuromuscular blockade

Occur in up to 25% of patients on mechanical vent > 1 wk Usually but not always recover; often prolongs period of time on ventilation

When things go wrong: Neuromuscular Disorders Many conditions cause ↓ capacity (stroke, spinal cord injury, ALS, phrenic nerve injury, Guillan-barre, myasthenia gravis, MD)

Spinal cord injury: C-3-4-5…

Site of cervical cord injury Muscles affected Results

Lower Accessory / expiratory muscles Diaphragm spared

Weak cough pneumonia

Higher Diaphragm affected (+others) Need long-term ventilation

Diaphragmatic Paralysis

Causes Features

Unilateral Cardiac surgery, trauma, tumor, stroke, herpes zoster

Relatively Asx (DOE)

↓ max voluntary vent (25%)

Bilateral Neuropathies, herpes zoster, vasculitis, Lyme dz

Severe dyspnea & ORTHOPNEA (really bad)

↓ VC and max voluntary vent (50%)

Diagnose by Pdi (transdiaphragmatic pressure – balloon in esophagus vs stomach)

↓ respiratory drive: either won’t breathe or can’t breathe

Drug OD or CNS disorders of central drive can cause

When things go wrong: Obesity

What’s wrong? Why’s it bad?

RM oxygen consumption ↑↑ (can reach 15% total) o ↑ work of breathing, have to move all that extra mass

RM force ↓ (especially supine – same as above)

RM endurance ↓

Makes you less tolerant:

Of any lung disease

Of low respiratory drive

33

Assessment of RM Function Simple clinical observation: “TAP”

Tachypnea

Accessory muscle use

Paradoxical breathing o Put one hand on abdomen, other on chest: should rise & fall together. If diaphragm can’t contract, not raising

abdominal pressure. Accessory muscles contract, suck abdominal contents in abdomen falls

o Respiratory alternans: periods of alternating paradoxical & normal breathing Diaphragm works for a while, takes a break & lets accessory muscles work, etc.

Blood gases: hypercarbia (but a LATE sign! Very ominous if rising – some pts can have chronic hypercarbia) Maximum inspiratory / expiratory pressure (MIP/MEP)

Measurement of global inspiratory or expiratory strength

Inhale / exhale against occluded airway

Varies with lung volume o Max MIP at RV (the whole way down, easiest to inhale) o Max MEP at TLC (totally expanded, easiest to exhale)

Transdiaphragmatic Pressure (Pdi)

MIP/MEP measure all muscles together

Pdi is specific for diaphragm

Treatment of RM failure Muscle training (exercise) – works for skeletal muscle but NOT for resp muscle

Works in normals (↑ strength / endurance) but not patients

Problem: already exercising resp MM all the time (e.g. COPD) Rest (mechanical ventilation)

Allow respiratory muscles to recover from constant load

Mechanical ventilation

o Non-invasive (nasal / facial mask with positive pressure), invasive (if intubated) o Temporary (endotracheal tube) or permanent (tracheostomy)

Medications: don’t really have any good ones!

Bronchodilators (dilate airways, ↓ hyperinflation)

Theophylline (↑ strength, ↑ resistance to fatigue)

Androgenic steroids (mixed results) Diaphragmatic pacing: rarely useful

Traumatic or resp. center injury, NOT for fatigue

Need intact phrenic nerves

Respiratory muscle surgery : Lung volume reduction

Used infrequently these days

Severe emphysema: ↑RM strength by ↓ hyperinflation

↑ lung fxn, sx, survival in some pts, but unpredictable outcomes

Treatment strategies

Exercise

Rest

Medications

Pacing

Surgery

Key Points (from slides)

RM failure manifested by hypercarbia

Diaphragm is main inspiratory muscle

Inspiration is impaired by hyperinflation

RM failure due to demand/capacity imbalance

Treated by restoring balance o ↓ workload or rest muscles with ventilator

34

Other risk factors for ARDS SEPSIS / trauma /gastric acid

aspiration

Older age

Severity of associated illness

Cig smoking / chronic lung dz

Chronic alcohol abuse

Acute Respiratory Distress Syndrome (ARDS) Biopsy: Diffuse Alveolar Damage (thickened alveolar/capillary septae, hyaline membranes) What is ARDS?

Acute lung injury of the alveolar-capillary membrane, characterized by:

o Permeability pulmonary edema o Acute respiratory failure

A syndrome (see box to right)

Routes of Injury Inhalation Blood-borne Direct injury to lung

Aspiration of gastric contents

Pneumonia (diffuse bilateral) Smoke inhalation

Near-drowning

Sepsis

Trauma Drug overdose (narcotics, ASA)

Multiple transfusions

Pancreatitis

Venous air embolism

Lung contusion

Radiation

Predisposing factors SEPSIS IS #1

40% pts with sepsis develop ARDS; 40% ARDS pts had sepsis as factor

Sepsis / trauma / gastric acid aspiration = 75% of cases Multiple factors multiply risk of ARDS development

Clinical Course of ARDS Variable onset of signs / symptoms

Direct lung injury (gastric aspiration, etc): explosive course (resp distress over min-hrs)

Blood-borne causes (sepsis, trauma, drug OD): gradual onset (hrs to days) Risk factor exposure 90% develop sx, on vent within 3 days

If you’re exposed to risk and don’t get sx within 3 days, you’re probably ok

Mortality: currently 30-40%; Most deaths within 2-3 wks (90%)

Early (<3 days): underlying illness

Late (>3 days): multi-system organ failure / nosocomial sepsis few (15%) from failure to oxygenate / ventilate (good at management)

Survivors: mostly NOT severely impaired

Pulmonary function: spirometry & lung volume nl by 6mo; DLCO stays at 70% by 12mo Functional recovery is slower (peripheral muscle weakness common @ 12mo)

CLINICAL DEFINITION OF ARDS

1. Acute respiratory distress.

2. Diffuse alveolar infiltrates on CXR

3. Severe hypoxemia (PaO2/FIO2 ≤ 200 mmHg) Example: PaO2 of 200 mm Hg on FIO2 = 1.0

4. Absence of left heart failure (pulmonary capillary wedge pressure < 18 mmHg)

35

Pathphysiology of ARDS 1. Injury to capillary endothelium (activated PMNs, Mϕ) cytokines, oxygen radicals, etc.) 2. Pulmonary Edema

o Protein rich (both water & protein leaking) o Sensitive to small increases in capillary pressure o Insensitive to changes in blood oncotic pressure

Normally:

fluid drains out (depends on Kf = conductance constant & driving pressure, combination of hydrostatic pushing out minus oncotic sucking into capillary)

Lymph channels drain lung, keep the alveolus dry

ARDS: damaged capillary endothelium

↑ Kf (leaky)

↓ σ (oncotic pressure keeps fluid in capillary less because proteins are leaking through)

↑ fluid filtration (Qf) as a result (Starling equation) edema

Pulmonary edema: leads to hypoxemia & ↓ lung compliance (CL)

Hypoxemia: Right to left intrapulmonary shunt o Refractory to oxygen; caused by alveolar flooding & collapse

Airway resistance ↑ (extra weight pushing on them, less tension pulling airways open) regional hypoventilation Alveolar instability: abnormal surface tension forces?

o V/Q mismatch too (same mechanisms as above, just not complete) – in transition zone

o NOT contributing: diffusion impairment or hypoventilation

↓ Lung compliance: lung is smaller & stiffer o Why?

↓ ventilated lung volume (alveoli compressed / closed) ↑ surface forces (surface tension ↑) ↑interstitial edema (heavier weight of lung itself) Fibrosis (later)

o All this means respiratory muscles have to work harder

Findings: CXR, CT, biopsy

tons of interstitial edema on CXR

Area of compression (shunt – no ventilation) with transition zone above (V/Q

mismatch)

Diffuse alveolar damage on biopsy Thickened alveolar/capillary membranes

Hyaline membranes

Diffuse inflammatory infiltrate

36

Management of ARDS: Oxygen Therapy Oxygen Therapy: main strategy for ARDS treatment PEEP: essentially raising FRC

Keep positive airway pressure at end expiration

Recruits more lung: stents open compressed airways & alveoli w/ +pressure o ↑ FRC, ↓ shunt fraction, ↑ compliance

Risks of PEEP:

↓ venous return ↓ cardiac output (↑ FRC ↑ resistance)

Barotrauma (volutrauma) – overinflate lung (pneumothorax!) ↑ dead space (ventilated but not perfused)

o squeezing shut alveolar capillaries; same reason why ↓ venous return)

Mechanical ventilation

Study: reducing tidal volume in mechanical vent lead to ↓ mortality, ↑ vent-free days, ↓ organ failure

Can cause more damage with overstretching!

Overall Therapy of ARDS: Summary No direct anti-ARDS treatment

Treat underlying problem (if possible)

Maintain O2 delivery and systemic organ fxn

Avoid complications: o Oxygen toxicity (keep FIO2 ≤ 0.60) o Ventilator-induced injury (keep tidal vol ≤ 6 ml/kg) o Nosocomial infections pneumonia, catheters

GOALS OF O2 THERAPY FOR ARDS

Arterial O2sat = 90% o (too high is toxic!)

Keep FIO2 ≤ 0.60

Maintain cardiac output

METHODS

Mechanical ventilation

PEEP (positive end-expiratory pressure)

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Pneumonia

Significance 7th leading cause of death in US

Leading cause among nosocomial infections

M. tb is most deadly bacteria in world

Pandemic influenza major geopolitical death

Generally, patients with pneumonia do well

(only 25% CAP hospitalized; 12% of those die)

Need to recognize, assess risk, Dx, Tx

Pathogenesis Pneumonia: infection of the lung parenchyma

Not one disease, but many common ones that share a common anatomic location Some non-infectious processes also are called “pneumonia” – e.g. eosinophilic pneumonia

Route of Infection

Many people think it’s inhaled respiratory transmission – but not most common way!

Most: colonization (oropharynx / endotrach tube) establish there aspirated into lung!

Route of transmission Organisms

Inhalation M. TB, Legionella, endemic fungi, viruses (e.g. flu), anthrax

Aspiration

Micro-aspiration S. pneumo, H. flu, GNB, S. aureus

Macro-aspiration

Anaerobes (esp. those found in mouth) – not as pathogenic (need more!)

People with seizure disorders, drug users, alcoholics, neuromuscular disorders, etc. – need big aspiration!

Mucosal spread Respiratory viruses Hematogenous S. aureus (from R-sided endocarditis)

Pathogens need to overcome host defenses

Angle of airways can change airflow problems!

Mucociliary escalator: sweep mucus upwards, cleared

Cough reflex (prevents aspiratory pneumonia)

Lots of stuff secreted; cellular components

If this gets messed up, you have ↑ susceptibility ↓ Host & ↑ Microbe: the “arms race”

Lowered host defenses Microbial virulence Impaired consciousness

Endotracheal intubation

Viral infection & smoking (knocks out mucociliary escalator)

Immunodeficiency

Antigenic drift / shift (Influenza virus)

Capsule (resist phagocytosis) (S. pneumo, Cryptococcus)

Evasion of phagolysosome killing (M. TB, Legionella)

Clinical Presentation Symptoms:

Fevers, chills, rigors (shaking) – cytokines, etc.

Cough, sputum production, dyspnea, pleuritic pain (sharp with inspiration / coughing) – when more established

Signs:

Infiltration crackles

Consolidation dull to percussion, tubular breath sounds

Pleurisy (friction rub – scratchy sound on insp.)

CXR: INFILTRATE (diagnostic!)

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Pneumonia vs Acute bronchitis: important for treatment

Pneumonia Bronchitis

Sx Cough & Fever Cough + Fever

PE VS: P >100,RR >24, BP Crackles, consolidation

Normal VS Rhonchi, wheezes

(except flu)

X-ray Infiltrate Negative

Etiology BACTERIAL VIRAL

Antibiotics? YES NO

Diagnosis: CXR Patterns

Consolidation

Lobar pneumonia

Lobar = restricted by fissure

Air bronchogram: outline of bronchi stand out against fluid-filled alveoli

No normal airflow: alveoli filled w/ fluid

Pneumococcal; other bacterial pneumonias especially

Broncho-pneumonia

Spotty, patchy infiltrate around central airways

Not a homogenous lobular pattern

Viral / atypical pneumonias especially

Interstitial pneumonia

Linear, reticular patterns (“web like”) Less dense, fluffier infiltrates

Inflammation in interstitium (fluid, not pus)

No air bronchograms

Viral / atypical pneumonias especially

Lung abscess or

cavity

Necrosis debris discharged via connection to airway (leaves cavity)

Air-fluid levels (if still some pus around) – means pyogenic bacteria (S. aureus, Klebsiella, oral anaerobes)

limited Ddx: GNR, S. aureus, M. TB, fungi

Infiltrate: hallmark of pneumonia

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Diagnosis: Sputum & Culture Quality of sputum:

Polys Squamous epithelial cells

Grossly From

Good: Lots Few Thick mucus Lower resp tract Bad: Few Lots Saliva Upper resp tract

Can be mixed too: believe type III, consider type II, throw out type I

Graded by lab Picture: left is good (thick sputum with polys); right is bad (saliva with epithelial)

Is what you isolated the cause?

Probable Cause Definitive Cause

Likely pathogen isolated from resp secretion that…

Is screened to distinguish sputum with saliva

Gram stain: predominant pathogen c/w culture result

Culture: Moderate to heavy growth

Can’t call it definitive if it could be there for other reasons!

Likely pathogen isolated from normally sterile site (blood, pleural fluid)

OR

Definite pathogen isolated from resp secretion – these guys are never incidental! o Bacteria: Legionella, mycoplasma, M. TB, B. anthracis o Viruses: Influenza, paraflu, RSV, SARS o Fungi: Pneumocystis, endemic fungi

Other rapid ID techniques:

Antigen detection / IF (urine, resp. secretions, blood), Nucleic acid amplification (resp secretions), Ab detection (blood)

Clasisfying Pneumonia Acute vs Chronic

Acute evolves over hours / days (S. pneumo, H. flu, Legionella – fast growers)

Sub-acute / Chronic evolves over weeks-months (M. TB, fungi, anaerobic abscesses, PCP – slow growers)

Community acquired vs Nosocomial (hospital-acquired) – for acute pneumonias

Community-acquired no significant exposure to healthcare system S. pneumo, mycoplasma, chlamydia, H. flu

Hospital-acquired Onset >48h after admission S. aureus, Pseudomonas/GNRs, Enterobacteriaceae

Community-acquired pneumonia Causes:

Bacterial (80%) > Viral (15-20%) ≫ Fungal (1-2%) > parasites ( < 1%)

See chart: * = not commonly isolated from sputum / blood

Treatment: often EMPIRIC (and successful)

Common Less common

Strep pneumoniae

H. flu

Legionella *

Mycoplasma pneumoniae*

Chlamydia pneumoniae*

Viruses*

Staphylococcus aureus

Moraxella catarrhalis

Gram-negative bacilli

Anaerobic bacteria*

Respiratory syncytial virus*

Parainfluenza*

Adenovirus*

Metapneumovirus*

SARS coronavirus*

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Classification of CAP: typical vs. atypical

“Typical” pneumonia “Atypical” pneumonia Onset Acute Subacute

Symptoms Fever / chills / Rigors Nonspecific, systemic, more viral: Headache, pharyngitis, myalgias

Cough Productive of purulent sputum Non-productive cough Lung exam findings Consolidation Few findings

CXR Dense infiltrate Patchy / interstitial infiltrate Leukocytosis YES (WBC > 15k) Modest (WBC < 15k) Etiology Strep pneumoniae, H. flu M. pneumoniae, Legionella sp., Chlamydia sp, viruses

Mycoplasma & Chlamydia Sp

Symptoms relatively mild (“walking pneumonia”); mortality basically nil

Won’t ID agents with routine studies

Mycoplasma: can cause extrapulmonary dz (hemolytic anemia, neuro sequelae)

NOT RESPONSIVE to β-LACTAMS: cover with tetracycline, macrolide, fluoroquinolone

Legionellosis

Epidemiology: 2-5% of CAP, sporadic in general pop, epidemics (hotels, hospitals)

At-risk: age > 40, COPD, immunosuppressed (old, smoking / drinking too much – like a Legionnaire)

Dx: urinary antigen detects 80% (doesn’t grow well)

Treatment: macrolide or fluoroquinolone

MORTALITY: 10-20% !

Influenza

Epidemiology: common (seasonal), also pandemic (drift/shift)

Mortality: 36k/yr, esp. elderly elderly

Sx: high fever, myalgia, headache, cough

Dx: clinical Dx > Ag test > culture

Rx: amantadine / neuraminidase inhibitors (give w/in 36hrs)

Prevention: vaccine (70-90% efficacy, ↓ severity), antiviral px, respiratory isolation, good resp precautions

Influenza can lead to bacterial superinfection (bacterial pneumonia 2° to influenza)

1° influenza pneumonia Bacterial superinfection

Course Progressive Transient recovery from influenza, then relapse Sputum High titers of virus S. pneumo, H. flu, S. aureus, GAS Rx Antivirals, supportive care Pathogen-directed Abx

Aspiration Pneumonia Frequency: ≈ 10% CAP, common cause of HAP At-risk: Macro-aspiration (alcoholism, drug abuse, seizure disorder, neuromuscular disorder) Sx / signs: Cough, fever, infiltrate in dependent segment (GRAVITY) Dx: usually clinical:

at-risk host +

subacute course +

putrid sputum (anaerobes) +

compatible CXR +

no other pathogens ID’d

Treatment: Clindamycin, β-lactam + metronidazole, β-lactam / β-lactamase

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Where’s it coming from? Gingival crevice!

Anaerobes, etc.

See polymicrobial flora on gram stain but nothing grows on Cx (anaerobes!) Chemical pneumonia involved too (acid!)

Organisms in aspiration pneumonia take a while to establish themselves

Acid burn of gastric contents rapidly develop pneumonitis o If no bacterial involvement: transient, no Abx needed

Aspiration pneumonia: if bacterial agents get involved, ends up in dependent locations (GRAVITY)

Lower lobe if standing up

Right middle lobe if laying down / on back

Often lead to abscesses!

Abscess vs Cavity

Aspiration pneumonia, etc.

Often see air-fluid levels M. TB, etc. – infectious, need respiratory isolation Upper lobe, esp. apical location; No air fluid levels

Nosocomial Pneumonia Hospital pathogens: Gram (-) bacilli, S. aureus Hosts are compromised:

HIV, cancer Rx, neutropenia, elderly

Mechanical defenses impaired: NG tubes / ventilators ↑ aspiration risk: impaired consciousness (anesthesia), procedures ↑ exposure to other pts: Legionella, RSV, influenza, TB, SARS Treatment

Empiric: BROADER spectrum than CAP (more possible causative agents)

Pathogen directed when you figure out what it is Prevention

Proper infection control (↓ transmission)

Identify aspiration-prone patients, ↑ HOB

Avoid unnecessary antacid therapy (↑ bacterial contents in stomach ↑ infection if aspirate)

Limit ventilator time

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Immunocompromised pts Type of defects depend on what kind of immune compromise you have (what usually clears the infection?)

Table for reference; probably wouldn’t memorize

Asplenia ↑ susceptibility to encapsulated organisms

TYPE OF DEFECT EXAMPLE(s) MAJOR PATHOGENS

Humoral agammaglobulinemia S. pneumoniae, H. influenzae (N. meningitidis)

Asplenia Sickle cell disease, traumatic or surgical asplenia S. pneumoniae, H. influenzae (N. meningitidis)

Neutrophil dysfunction chronic granulomatous dz S. aureus, Serratia, Burkholderia, Aspergillus, Nocardia

Neutropenia Aplastic anemia, cancer chemotherapy, congenital Gram-negative bacilli, Aspergillus sp.

Cell-mediated immunity AIDS, steroids, organ transplant recipients, cancer chemotherapy, lymphoma

Pneumocystis, Mycobacteria, Nocardia, Fungi, Legionella sp. Herpesviruses (CMV, HSV)

HIV: CD4 count what kind of infection you’re susceptible to (table for future reference too)

CD4+ Pathogens

>500 S. pneumoniae, H. flu

200-500 S. pneumoniae, H. flu, M. TB

50-200 S. pneumoniae, Pneumocystis jiroveci, H. flu , M. TB, Histoplasma, Cryptococcus

<50 S. pneumoniae, P. jiroveci, M. TB, Other mycobacteria, H. capsulatum, C. neoformans, Aspergillus sp., Nocardia sp., Rhodococcus equi, CMV, Kaposi’s sarcoma

Pneumocystis jiroveci (formerly carinii)

Frequency: up to 90% AIDS-associated pneumonia

Sx: Cough, dyspnea, fever (x 3+ weeks)

Dx: Induced sputum, bronchoscopy, open lung Bx

Rx: TMP/SMX, then HAART

Mortality: 100% w/o Abx; 17% hosp pts + Abx

Prevention: Abx px, HAART

CXR in Immunocompromised Patients (another one not to memorize but future reference) CXR Finding Associated pathogens

Diffuse interstitial infiltrate Pneumocystis, CMV, Kaposi sarcoma, respiratory viruses Diffuse nodular infiltrate (miliary) Mycobacteria, Histoplasmosis, other fungi, Pneumocystis Localized infiltrate Typical bacteria, Nocardia, Fungi, Mycobacteria Large nodular/cavitary infiltrate Staph aureus, Mycobacteria, Nocardia, GNR, Aspergillus, other fungi, anaerobes (aspiration) Hilar adenopathy Mycobacteria, fungi, Kaposi sarcoma, lymphoma

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Etiology by Age Newborn (0-6 wks)

Children (6 wk–18 yrs)

Young adults (18-40 yrs)

Middle age** (40-65 yrs)

Elderly** (> 65 yrs)

Group B strep

GNR

Chlamydia trachomatis (4-6 wks)

H. flu

Mycoplasma

Viral***

Mycoplasma

C. pneumoniae

S. pneumoniae

Pneumocystis

carinii (AIDS)

S. pneumoniae

Anaerobes

H. influenzae

S. pneumoniae

Anaerobes

H. influenzae

GNR

Viral***

Agents are listed in rank order ** Major causes of nosocomial pneumonia:

GNR (Klebsiella sp., P. aerug, Enterobacter sp., and E. coli),

S. aureus, anaerobes

*** Major viral pathogens

RSV, parainfluenza, and adenovirus

middle-aged adults: only common viral cause is influenza.

Treatment of Pneumonia Who should I be worried about? (Predictors of BAD OUTCOME)

Older age

Co-morbidities (malignancy, cardiopulmonary dz)

Alterations in host defense (don’t use bacteriostatic abx!)

Marked derangements in vital signs

Multiple lobe involvement

Bacteremia Treatment

Often empiric, usually successful

Narrow spectrum when pathogen-directed

↑ need to identify specific pathogens if: o Severe disease o Host immunosuppressed o Unusual features (e.g. cavity) o Failure to improve

Summary of Important Points Role: Most important infectious disease! Agents: Pneumococcus, Legionella, Influenza, mouth flora, M. tuberculosis Distinctive pathogens: Age, CAP, HAP, Compromised host Diagnostic evaluation: Poor yield, colonizers in respiratory specimens, few rapid diagnostics Treatment: Usually empiric abx and usually successful

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The Pleural Space

Anatomy Review Lined by parietal & visceral pleural (merge @ hilum)

Pleural cavities separated by mediastinum

2000 cm2 of surface area, 10-20 μ in diameter (thin) Villi on mesothelial cells (very metabolically active), stroma too Visceral pleura: NO SENSORY FIBERS (if patient says “ow”, it doesn’t mean you hit the lung)

Pleural fluid: generally produced on parietal side

From: Pleural capillaries primarily o Parietal: intercostals, internal mam. arteries o Visceral: bronchial & pulmonary arteries o Some from interstitium too

Intrathoracic lymphatics important for draining Peritoneal cavity: can have peritoneal fluid go up into pleural fluid in some disease states

Normally: slightly negative pleural pressure (lungscollapse, chest expand) – suck fluid in

Starling Equation: what determines movement of liquid into pleural space from capillaries??

𝑄𝑓 = 𝐿𝑝 × 𝐴[ 𝑃𝑐𝑎𝑝 − 𝑃𝑝𝑙 − 𝜎𝑑 𝜋𝑐𝑎𝑝 − 𝜋𝑝𝑙 ]

Basically: ↑ with ↑ surface area, permeability of

membrane to H2O, pressure difference between capillary & pleural space. ↓ with ↑ oncotic pressure difference (& ↑ impermeability of membrane to proteins

What causes ↑ pleural fluid?

Normally produce 0.01 cc/kg/hr

Lymphatics: can take up ≈ 0.28 cc/ kg/ hr (28x production!)

So you need either ↓↓ lymphatic flow or another process to get pleural fluid build up Normally 8 cc pleural fluid per side

1-2 g protein / 100cc; 1400-4500 cells / μL, mainly Mϕ, monos, lymphs

Need optimal amount for normal respiration (transpulmonary pressure maintenance, easy sliding)

Pleural effusions Causes of Pleural Effusions

Increased Production Decreased Clearance ↑ intravascular pressure / interstitial fluid

o LV / RV failure, PE, pneumonia, SVC syndrome, pericardial effusions

↓ pleural pressure o Atelectasis, ↑ elastic recoil pres.

↑ pleural fluid protein

↑ permeability o pleural inflammation, VGEF

↑ peritoneal fluid

Disruption of thoracic duct / intrathoracic vessels

Iatrogenic

lymphatic obstruction is #1 o 28 fold capacity for drainage vs normal

production

↑ systemic vascular pressures o SVC syndrome, RV failure

? disruption of aquaporins

o 4 types found in the lung;

o AQP1 important in peritoneal fluid transport

Qf = liquid movement Lp = filtration coefficient (H20 conductivity of membrane) A = surface area of membrane P / π = hydrostatic and oncotic pressures σd = solute reflection coefficient

• ability of membrane to restrict large molecules • capillary permeability (VEGF)

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Epidemiology: CHF (500k), Parapneumonic (300k), Malignant (200k), PE (150k), Viral (100k) are big ones

o Parapneumonic = related to pneumonia!

Also: Cirrhosis/ascites, post-CABG, GI dz, TB, mesothelioma, asbestos exposure

Clinical features: due to underlying cause of effusion

DYSPNEA: 57% o 1° due to large effusion: alteration in chest wall PV curve o Like emphysema

Cough, chest pain (dull in malignant, pleuritic in benign)

Fever: more in benign disease

Thoracentesis (taking fluid out of pleural effusion)

Indications Contraindications Unless you know why it’s there, take it out!

Especially if:

Unilateral effusions, particularly L-sided*

Bilateral effusions of unequal size*

Normal cardiac silhouette on CXR*

Febrile, evidence of pleurisy (* = indicates that effusion’s less likely to be transudate)

For relief of dyspnea too

Absolute & relative

Bleeding, infection

pneumothorax (1.3-20%, 2% need chest tube placed)

Also: o vasovagal episodes / arrhythmia, o tumor seeding of needle tract, o puncture of other organs, o re-expansion pulmonary edema o death (rare)

Visualize the effusion

CXR (can lay down in lateral decubitus to help see level)

Ultrasound o good for ICU, small effusions, trauma, teaching o U/S is really the standard of care these days

Go OVER THE RIB

Superior side – avoid intercostal vessels / nerve

Go more laterally (avoid intrathoracics, etc)

Transudates & Exudates Two types of pleural effusions: transudates / exudates; different clinical significance & etiology

Transudate Exudate

Cause Hydrostatic or colloid pressure imbalance Inflammation / disease of pleura

Pleura Intact Damaged

Major causes CHF, PE, cirrhosis (almost all cases!)

Pneumonia, malignancy, PE, GI disease (>90% cases are one of these 4)

Other causes Nephrosis, peritoneal dialysis, pericardial disease, hypoalbuminemia, Glomerulonephritis, sarcoid, SVC syndrome, urinothorax, myxedema

Tons (huge DDx) CHF:can produce exudative effusion post-diuresis

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Is it an exudate? Get both peritoneal fluid & serum LDH + protein compare.

Need one of the following (looking for ↑ leakage into pleural fluid) o Fluid : Serum protein >0.5 o Fluid : Serum LDH >0.6 o Fluid LDH >200 IU/L or > 0.45 upper limit nl for lab

If no serum labs: can use pleural fluid protein / LDH levels alone (not as good) o (protein > 2.9, LDH > 60% upper limit nl, chol > 45 mg/dL)

If you suspect a transudate, check serum – fluid albumin gradient

Transudate if > 1.2 g (not leaking albumin)

Other things to do:

Check the appearance of the fluid: serous, serosanguinous, purulent (empyema), etc? Closed pleural biopsy is good for TB (stick needle in, try to rip off some pleura)

Parapneumonic Effusions (PPE) & Empyema Parapneumonic effusion = effusion after pneumonia (40-57% pts with bacterial pneumonia develop PPE)

No clinical difference but ↑ mortality (3.4-7x), especially with delayed drainage (16x)

DON’T WAIT to treat – “never let the sun set on a pleural effusion” PPE empyema (pus in pleural space) in 10-20% PPE

Up to 58% overall mortality! Don’t wait to treat a pleural effusion! These can move quickly (e.g. PPE air pockets rupture)

PPE, can treat by draining Hours later: air pockets develop with gas production, would need surgery

After days / weeks: can rupture, requiring thoracotomy (major surgery)

Therapy for PPE

ABX: based on local prevalence, resistance

DRAIN IT: o Chest tube ± fibrinolytics o Thorascopy, thoracotomy, open drainage

Malignant Effusions #2 cause of exudative effusions (200k/yr in US), #1 for exudative effusions that need thoracentesis Lung cancer, breast cancer, lymphoma responsible for 75%

1° tumor not identified in 6%

BAD SIGN: Die in average of 4 months – PALLIATE by treating effusion o Primary tumor is most important predictor; performance status too

Pathogenesis:

tumor emboli visceral pleura, 2° seeding of pleural space / parietal pleura (or via diaphragm)

1° tumor Survival

GI CA 2.3 mo Lung CA 3 mo Breast CA / unknown 5 mo Mesothelioma 6 mo

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Work-up of malignant effusions:

Thoracentesis (cytology beter than closed pleural Bx)

Thorascopy (95% sensitivity)

NOT Bronchoscopy (little value!)

Treatment: for palliation

Don’t use much sedation – no nerves in visceral pleura

Go in and remove malignant nodules

Talc blown in (acts as glue to hold lung to chest wall;

also prevents re-accumulation of fluid)

Pneumothorax Moving from fluid (effusion) to air (pneumothorax) in pleural space Pneumothorax: AIR in the pleural space

Spontaneous o Primary (tall, thin males – paraseptal emphysema?) o Secondary (HIV, other underlying disease)

Traumatic (stab wound, etc) Presentation: depends on size & co-morbidities

Small pneumothorax Tension pneumothorax

R. apical pneumothorax; white line is visceral pleura; more radiolucent above (no lung features)

R. tension pneumothorax; lung collapses entirely filled with air (more radiolucent), mediastinum shifts away from

air (to left in this case)

Tension pneumothorax:

Tachycardic: shock death

Need needle decompression HR returns to normal immediately! PTX Treatment: depends on signs, symptoms / 1° vs 2°

Observation

100% O2 4-6x ↑ in rate of absorption

Tube thoracostomy

Take Home Points Pleural fluid accumulation results from:

imbalance in hydrostatic / oncotic pressure

Lymphatics are important for drainage

Drain effusions EARLY! Prior to getting a chest CT! Drain ‘em dry!

Malignant effusion palliate early!

Pneumothorax: can be life threatening

Paramalignant Effusions (not all effusions in cancer are malignant effusions)

related to primary tumor but

not direct neoplastic involvement of pleura

Etiologies: Post-obstructive pneumonia PPE, obstruction of thoracic duct

chylothorax, PE, SVC syndrome, post-obstructive atelectasis ↓ PPL, low Ponc from cachexia, pneumonitis/trapped lung, cancer Rx, more

Pneumothorax: Physical Exam

↓ breath sounds

↓ fremitus

Hyperresonance

Tracheal deviation

Hypotension

Tachycardia

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Bronchopulmonary Dysplasia BPD Definition: Premature infants who require oxygen or ventilatory support beyond 36-wks post-conceptional age

A.k.a. “premature lung disease of infancy” Relatively new disease (1967), pulmonary disease after resp therapy of IRDS (↑ O2 conc, mechanical vent)

airway inflammation, fibrosis, smooth muscle hypertrophy

high mortality rate

Premature births in US

11% all US births < 37 wks (premature)

308k with low BW (<2500g), 58k with very low BW (<1500g)

Complications of prematurity: not just lung problems in these infants!

BPD

intraventricular hemorrhage

periventricular leukomalacia

necrotizing entercolitis

retinopathy of prematurity

In US, bronchopulmonary dysplasia is the leading cause of chronic lung disease in infants

BPD can also occur in up to 20% of mechanically ventilated FULL TERM infants

Pathological Findings ATELECTASIS, OVER-INFLATION, CYSTIC CHANGES

Treatment Has really ↑ survival for very early gestation infants

Use of bovine surfactant

Tertiary care centers take care of infants

Better ventilator techniques (less damage)

Prudent supplemental O2 use o (high concentrations free radicalsimpairs alveolar growth) o Remember lung keeps growing & developing (until 2 yo)

Exogenous surfactant: made huge change in these infants

↓ airway surface tension

↓ IRDS incidence in premature infants

Can work really fast (6 hrs in picture to right!)

Hyperinflation, interstitial changes, cystic development

“Mosaic changes” on CT: dense areas, hyperinflation

Histology: areas of atelectasis, other areas with alveolar enlargement; fibrosis rxn

Common features of BPD

Abnormal CXR

Respiratory symptoms

Hx of supplemental O2 and/or mech vent in neonatal period

49

Surfactant review Surfactant:

Formed in lamellar bodies in type II pneumocytes

Secreted, forms monolayer in air-liquid interface

↓ surface tension Surface tension: directly proportional to pressure needed to open & keep open alveoli

LaPlace’s Law: Pressure =2×tension

radius

If ↑ surface tension, need ↑ pressure to keep open (newborn with RDS: collapse!)

BPD in Extremely Low Birth Weight Infants Exogenous surfactant: doesn’t ↓ incidence of BPD in extremely low birth weight infants

BPD extremely common in extremely low birth weight infants (52% 500-750g, ↓ with ↑ wt) “New BPD”: FEWER & LARGER alveoli (alveolar hypoplasia)

Secondary to developmental arrest in canalicular stage (16-24 wks gestation)

Fewer alveoli, smaller SA of lungs (see picture) problems

Extremely premature infants have ↓ surface area

BPD Risk Factors 1. Positive pressure ventilation

a. causes inflammation, problems in lung

2. Infection a. Immune systems not developed b. pre/post-natal infections

3. Inhibition of alveolar growth

a. nutrition (malnutrition) b. steroids / oxygen (double-edged swords)

How to prevent PBD Prevent premature delivery

Avoid mechanical ventilation in preemie infants when possible o consider high frequency ventilation (smaller volumes) and permissive hypercapnia

Steroids – double-edged sword o Prenatal –OK

o Avoid postnatal when possible (esp. first week of life)

Avoid infections in mother and infant

Maximize calories in preemie infants to prevent malnutrition

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Diagnostic Criteria (severity of BPD) If born ≤32 wks gestation & got >21% O2 for 28+ days: assess at 36 wks PMA or at time of discharge

Mild BPD Breathing room air

Moderate BPD Need < 30% O2

Severe BPD Need ≥ 30% O2 and/or positive pressure (nasal CPAP / PPV)

↑ need for pulm meds, hospitalization in follow up studies if more severe BPD Respiratory Syncitial Virus: RSV

Infection High morbidity & ↑ mortality, especially in BPD infants

Out to 2-3 yrs, ↑ RSV hospitalizations in BPD infants

Respiratory Symptoms of BPD Fast breathing

Wheezing

Ronchi / crackles

Retractions and/or head bobbing (bad sign)

Cough with gagging / emesis (breathing really fast – hard to take bottle)

Cyanosis with exertion

Medical treatment Meds

Diuretics consider if need supplemental O2

Preterm > 3wks – acute / chronic distal diuretics may improve pulmonary mechanics

Inhaled steroids BPD infants have ↑ airway resistance & inflammation

β-adrenergic bronchodilators use PRN (can develop tolerance)

Anticholinergics (nebulized ipratroprium, etc)

can help in respiratory aspiration IRDS – kind of like COPD lungs in a mechanistic sense

Supplemental Oxygen

Hypoxia in BPD infants (formerly thought was ↑ SIDS) o ↑ number of central apneas o ↑ central apneas, hypoxia bradycardias, severe hypoxemia, inability to auto-resuscitate (death)

Maintain O2 sat: better growth / development, prevent central apneas / oxygen o ↓ risk of sudden death from acute hypoxia

Want O2Sat 92% or greater during sleep, with feeds, during activities Weaning off O2:

Consider if O2sat > 93%

Wean off during day first, assess growth over several weeks

Consider overnight sleep study before discontinuing at night Nutrition: need 120-150 kcal/day for adequate growth, supplemental tube feeding if needed

Exacerbation of respiratory Sx in BPD Aspiration during feeds

Gastroesophogeal reflux

GER + aspiration

Bronchomalacia / tracheomalacia (resolves by 2-3 yrs)

Vocal cord dysfunction / subglottic stenosis

Recurrent insults to lungs can worsen underlying BPD & prevent compensatory lung growth

Growth continues through 2 years – window for catching up!

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Pulmonary Outcomes in BPD infants Respiratory Sx in 25% young adults / adolescents who had BPD:

Wheezing (↓ small airway flows)

Recurrent pneumonia

Chronic need for resp meds

↓ exercise tolerance

Radiographic abnormalities

↑ risk of airway obstruction & reactivity (↓ FEV1)

Course:

Hospitalizations for resp problems ↓ by 4-5 yo

↑ frequency of chronic resp problems (esp. obstruction)

Wheezing ↑ smaller kids (in BW < 1500g

↓ resp reserve, ↑ O2 desaturation with exercise Non-respiratory issues too!

1/3 require physical, occupational therapy, technical aids

One of most costly chronic childhood diseases

Impact on everyday family function (big problem esp. if ↓ socioeconomic class)

Severe disabilities (22% @ 6 yrs) – e.g. cerebral palsy, blindness, profound deafness o Boys > girls

Cognitive impairment in 41% at 6 yrs

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Cystic Fibrosis

Genetics of CFTR 1:2750 Caucasians, carrier rate 1:25

↓ in African Americans (1:17k), ↓↓ in Asians (1:70k)

CFTR : Single gene mutation o (chromosome 7, most common mutation is ΔF508) o cAMP-regulated chloride channel o Autosomal recessive

Manifestations of CFTR Systemic! Lungs Chronic obstructive pulmonary disease Pancreas Pancreatic exocrine insufficiency (↓ enzymes to digest fat) GI CFTR channel helps in stool transit Repro glands Can’t develop (e.g. vas deferens) Skin Sweat electrolytes ↑ (sweat test, messed up salt balance)

Respiratory Manifestations Chronic cough and bronchitis at first

Bronchiectasis (no matter how well you treat)

Recurrent pneumonia (staph aureus, pseudomonas aeruginosa)

Chronic sinusitis, nasal polyps

Hemoptysis, pneumothorax (↑ pressure cysts can pop!)

Chronic airways obstruction, irreversible

CF lung disease starts as endobronchial infection

Max prevalence Other notes

Staph aureus 50% age 5-17 yrs H. flu 25% age 2-5 now vaccine so ↓ incidence Pseudomonas aeruginosa peaks age 18 & remains throughout life mucoidy, makes biofilms Burkholderia cepacia feared, very hard to treat

Progression of lung infections: 1. Bacterial endobronchial colonization

2. Intense inflammatory rxn

3. Obstructive lung dz with superimposed

pulmonary exacerbations o (↑ cough, sputum, dyspnea, ↓ PFTs;

wt loss, fatigue, rarely fever)

Can require intermittent abx Oral / IV / inhaled

Airway clearance, bronchodilators, anti-inflammatories too

Don’t let it progress – INTERVENE EARLY Need to be able to clear mucus (multidimensional treatment approach)

Diagnosis by CLINICAL TRIAD:

↑ SWEAT CHLORIDE

PANCREATIC INSUFFICIENCY

CHRONIC PULMONARY DISEASE

Submucosal glands dilated, hypertrophied. Airways are the problem – mucus plugs, surrounding inflammation in response. CXR: patchy, white, interstitial inflammation; Lungs: bronchiectasis

Findings in Lung

53

Complications of CF lung disease Hemotypsis: bronchiectasis, dilation of brachial arteries

Control with abx, embolization

Pneumothorax: dilated peripheral airways + mucus plugging / air trapping, rupture of pleura Chest tubes, pleural sclerosis involved too

50% recurrence rate See these more frequently in adults now: about 1/3 CF pts are adults these days

CF Upper airway disease Nasal polyposis (shouldn’t see nasal polyps in child)

Nasal polyps + asthma in child: 99% of time it’s CF!

3% CF pts; tx with topical steroids, surgical excision

Pan-sinusitis: maldevelopment opacifiction, erosion

All CF pts; Tx with abx, surgery

CF GI disease GI Sx start early: pancreas blocked, no good in utero production of fat metabolizing enzymes

Meconium ileus (newborn) ≈ Distal intestinal obstruction syndrome (postnatal) – GI blockage o Can lead to intussusception (telescoping of bowel into itself, can cause death)

Meconium peritonitis too

Pancreatic insufficiency is lifelong (malabsorption)

Hepatic cirrhosis, portal HTN, neonatal direct hyperbilirubenemia, gall bladder obstruction Nutritional aspects (edema, hypoalbuminemia, hypovitaminosis A/K/E) – more rare these days

DIOS: Distinal Intestinal Obstruction Syndrome Not secreting chloride stool accumulates at ileal/cecal junction

o Esp if pt out in heat, gets a little dehydrated

Can densely adhere to wall intussusception, currant jelly stools, blood Tx with pancreatic enzymes, osmotic laxatives, enemas, even surgery

Pancreatic Disease ↓ volumes & bicarb content of pancreatic fluid

15% have milder mutation pancreatic sufficiency (longer life span but ↑ risk pancreatitis!)

Can lead to CF-related diabetes (3% kids, 14% adults) o Block islets ↓ insulin and ↓ glucagon (so ketoacidosis rare) o Stresses can trigger hyperglycemia: pregnancy, corticosteroids, pulmonary exacerbation

Hepatobiliary Dz Eosinophilic concretions in bile ducts ↑ gall bladder dz, gall stones, microgallbladder

Cirrhosis in 3%: portal HTN, splenomegaly, esophageal varices

Congenital Absence of Vas Deferens Most CF males absent / atretic vas deferens azoospermia, infertility

o Even with mildest mutations

Dx with palpation or U/S

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Diagnosis of CF

Sweat Test Classic test; still used as primary test

Pilocarpine to stimulate cholinergic pathway of sweat generation o collect w/ filter paper, measure salt

CFTR: reabsorb chloride to protect from dehydration o So if there’s too much chloride (very salty sweat), CF o ≥ 60 meq / L chloride is high

Other causes too! (but usually CF) Varies with age: up to 80 in some adults, ≥ 30 meq/L suspsicious in young infants When should I get a sweat test? (these things mostly make sense) Meconium ileus, meconium peritonitis

Jaundice in infancy

Hypochloremic alkalosis in infancy

Heat prostration Infancy/adulthood (males)

Failure to thrive Infancy/childhood

Rectal prolapse in childhood

Nasal polyposis in Childhood/adulthood

Panopacification of sinuses/pansinusitis in childhood

Pancreatitis in late childhood/early adulthood

Unexplained cirrhosis in childhood/adolescence

Gallstones in late childhood/early adulthood

CBAVD/Azoospermia at any age (but becomes more obvious in adults)

Recurrent or persistent pneumonia any age

Staphylococcal pneumonia at any age (especially infants)

Mucoid Pseudomonas in lung at any age

Bronchiectasis at anyage Family history (sibling, first cousin)

Immunoreactive Trypsin Most CF patients develop ↑ immunoreactive trypsin, but 80% false positive rate

Dx by Genotyping 1000x mutations in CFTR; internet databases; don’t know significance of all

Commercial genotyping available CFTR: an ABC Transporter

ΔF508 is the classic mutation (European) o 44% homozygous o 45% heterozygous o 11% non-ΔF508

Classes of Mutations in CFTR I-III: more serious

I. Stop codons (no synthesis) II. ΔF508 (block in processing, both not fully

constructed & doesn’t make to surface) III. Regulation: can’t open with cAMP

(pancreatic insufficiency CF if 2 serious mutations

IV-V: milder mutations (If one serious, one milder: mild dominantes - milder phenotype)

IV. Altered conductance V. Reduced synthesis

CFTR has a spectrum of pheonotypes

Heterozygous, / mild mutation – maybe asthma modifier

CF Syndrome: maybe mild mutations only sinusitis alone (atypical CF phenotype)

Cystic fibrosis: Severe/Severe genotype

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Organ-Specific Vulnerabilities Organs that make lots of protein & secrete slowly through long tortuous passages

Genotype: predictive of pancreatic sufficiency but not other diseases (meconium ileus, liver dz, diabetes)

Pulmonary Status Variable rate of decline (even with identical genotype)

Complex structure / function, main cause of morbidity / mortality

↑ CFTR carrier frequency in… Obstructive azoospermia

Idiopathic pancreatitis

Allergic bronchopulmonary aspergillosis

Disseminated bronchiectasis

Diffuse bronchiectasis associated with rheumatoid arthritis

Sinusitis

(Sarcoidosis)

CF Treatments Aspect of CF Treatment

High Sweat Chloride Dietary Salt (a disease you ↑ salt for!)

Thick Airway Mucus Chest Physiotherapy/DNase Hypertonic Saline

Chronic Lung Infections Antibiotics Inflammation Anti-Inflammatories

Respiratory Failure BiPAP Lung Transplant

Pancreatic Insufficiency Pancreatic Enzymes Meconium Ileus PEG, stool softeners Islet Cell Loss Insulin, Pancreatic Transplants Male Infertility, CBAVD In Vitro Fertilization Biliary tract insufficiency Bile acid salts

Some Data and Stuff Better survival with more recent birth cohorts

↑ with nutrition, vitamins, enzymes, abx, better tx / analaysis of data / use of registries (best practices)

FEV1 ↓ with age but ↑ with BMI

Try to keep BMI of CF pts up! Respiratory severity ↑ with age (more normal lung fxn in children)

Once you lose it, won’t get it back Bacterial infections vs time

Pseudomonas: 80% pts from 25-34 yo

↑ MRSA these days

B. cepacia – especially bad Lung transplant: not a good solution; limited organs available, tons of side effects, risk of death

Trading one disease for another Median predicted survival now 38 years (↑ but still – only 50% live to be 38!)

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Disorders of the Lower Airways “When noisy breathing is not asthma”

Clinical Approach Physical Exam of the Chest

Inspection: Vital signs (resp rate, SaO2), retractions, contour

Percussion (dullness vs hyperinflation) o Diaphragmatic domes normally w/in 1-2 finger breadths of scapular tips

Palpation

Auscultation is the big one o Inspiratory or Expiratory o Airway disease = narrowing

(laminar vs turbulent air flow depending on radius) Something pushing in from outside!

Position Sound Ins/Exp More detail

Above thoracic output Stridor Inspiratory

Below thoracic output Wheezing Expiratory High pitched Peripheral (e.g. asthma) Coarse sound Central (larger airways)

Where do sounds come from? THE AIRWAY!

Turbulent = loud, laminar = quiet

Most from trachea, medium sized bronchi

Peripheral airways: nearly silent; contribute little to total resp resistance o Unless asthma / narrowing

Describing breath sounds

NORMAL ABNORMAL

Bronchial (tubular): equal loudness I/E

Vesicular: I>E, soft expiratory phase

Respiratory phase o Inspiration (stridor) or end-inspiration (crackles) o Expiration (wheezes)

Location (e.g., central or peripheral)

Quality (e.g., monophonic or polyphonic)

Lower Airway Lesions in Newborns & Infants “Wheezing since birth” – noisy on 1st day of life

Think congenital lesions (vascular ring, tracheal web, absent pulm valve, congenital lobar emphysema) o All result in tracheal compression – can see expiratory flow reduction

Congenital Thoracic Malformations: old nomenclature separated; now lumped together

Affected lobes remain filled with fluid at birth (radiodense), then later air

Recurrent infection is common complication, often with abscess formation (periphery)

Unaffected lobes: usually normal, can be compressed

Get an electrocardiogram (associated with cardiac abnormalities)

CTM: foregut cysts: Not pathogenic in and of themselves but press on other things; can get infected

Most common cyst in infancy (Sx = compression) but 50% diagnosed >15yo (Sx = chest pain, dysphagia)

History

Onset

Alleviating / exacerbating factors o Position o Occurrence: sleep or activity o Response to therapy

Other associated symptoms: COUGH (never normal in babies!)

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o Small incidence of malignancies

Tx: often lobectomy (no recurrence with complete excision)

CTM: Congenital cystic adenomatoid malformations

Often solid / fluid filled at birth air filled with time o Can see air-fluid level on CXR

Classification: related to location and potential for malignancy o Associations with other syndromes & malignancies

Tx: resection (esp. infection) most surgeons remove

CTM: Pulmonary sequestration

Pulmonary tissue separated from functioning lung and supplied by SYSTEMIC circulation

Etiology: 2 theories

o Congenital: accessory lung bud; primitive perfusion from systemic circ persists

o Acquired: focus of infection/scarring develops systemic blood source

Anatomy of pulmonary sequestration

Intralobar 75% (w/in parenchyma, usually L posterior basal)

Asx until infected (adolescence) (recurrent “pneumonia”, abscess formation, abnormal CXR)

Extralobar 25% (beneath L. lower lobe; perfused by abnormal artery coming from below diaphragm)

Detected in infancy (associated malformations) Diaphragmatic lesions, gut anomalies, polyhydramnios

Extralobar extrathoracic Rare

Treatment: surgical excision

Congenital large hyperlucent lobe Formerly “Congenital lobar emphysema” (CLE) Incidence: 1:20k-30k Etiology:

Mechanical obstruction in utero(25%) – mucosal flap, lobar twisting on pedicle

Airway collapse (25%) – bronchial atresia, deficient bronchial cartilage

No clear etiology (50%)

CXR: over inflated lobe

compressing trachea

pushes everything over to right

Hyperlucent(over inflated) – can get V/Q mismatch

Upper lobe disease: here LUL, most common, > RUL > RML, LL rare) Pathology: ↓ # alveoli, ↓ bronchial wall cartilage Treatment: expectant management (see if improves) – previously more excision

Some mechanical vent techniques might help (oscillatory vent if ventilated)

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Tracheoesophageal Fistula Incomplete mesodermal separation of primitive foregut

Esophagus connected to trachea o See barium swallow to right

More common: 1st and twin pregnancies; ↑ with ↑ maternal age

2/3 have other associated abnormalities

Presents around birth (feeding / breathing abnormalities) 4-5 different kinds:

H-type fistula: small connection between trachea & esophagus o Can present later: recurrent pneumonia / wheezing but rare

Esophageal etresia is most common (esophagus stops as blind pouch, distal esophagus connects to trachea) Can all be repaired surgically

Local tracheomalacia & brassy cough common after TEF repair o Malacia = “softening”

Esophogeal dysmotility (vagal disruptions) recurrent aspiration

TEF can recur after repair (very rare)

Vascular Rings Can show up early but often later in life

Extrinsic obstruction of trachea & esophagus

Most common: double aortic arch; can see others too o Wraps around trachea, compresses o Just sever one of arches (smaller one) everything OK

CXR: look for right sided arch (sensitive but not specific – common variant) Pulmonary swing:

Left PA originates from Right PA, courses posterior to trachea (see CT)

Results in tracheomalacia

Tracheomalacia / Bronchomalacia Dynamic collapse of trachea secondary to increased compliance of tracheal rings

Worse on exparation

Most common in distal 3rd

Can get kinking (transition from malacic segment to normal segment)

Babies: spells of apnea (collapse airway with crying, etc.) - dangerous

Laryngeomalacia Tracheo/ bronchomalacia

stridor, inspiratory, upper airway wheeze, louder on expiration

Many people have combo! Biphasic noise (may indicated fixed narrowing) Most gets better over time if not repeated injury from aspiration, other probs

Parents often aware of noisy breathing early but often don’t present until 6-12 mo

Fremitus is uniform, normal lung volumes (obstructing), lack of retractions, poor bronchodilator response

ALWAYS present if you have a TEF

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Bronchoscopy:

Left mainstem bronchus has keyhole appearance

Right mainstem bronchus has a lip (airway flopping into lumen)

Tracheal Bronchus If airway not built right (e.g. aberrant RUL bronchus coming off of trachea instead of bronchus)

Picture: ignore arrow, actually the top bronchus branching off early

Normal variant, predisposes to chronic RUL atelectasis o Pigs are all like this, so called “pig bronchus” too

Don’t need to do anything about it unless causing problems

Foreign body aspiration Can occur in any age, frequently toddlers / preschoolers (stick stuff in mouth)

Choking Hx often negative

Unilateral / “monophonic” WHEEZE (same tone throughout)

o Phase delay on differential stethoscope CXR often doesn’t help: most are radiolucent

may be difficult in younger pts to get insp/exp films

L-R decubitis films show absence of deflation Lack of response to all medical therapy

Chronic Congestion CHRONIC WET COUGH IS A RED FLAG – something else is going on! (wheezing + cough)

o Beyond just narrowing of airways o CF / primary/acquired dyskinesia, passive smoking, humoral immunodeficiency, retained foreign body

Gastroesophageal Reflux Disease Recurrent croup is often a sign of GERD (“spasmodic” with no sign of URI)

Hoarseness

Can lead to laryngomalacia (acid)

Poorly controlled asthma

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Bronchiolitis INFLAMMATION of BRONCHIOLES usu. occurring in children UNDER 2 YRS OLD resulting from VIRAL INFECTION

Disease of WINTER, infectious in nature

Pathophysiology

Airway obstruction o Airway wall edema o Mucous plugging o Bronchospasm

Increased airway resistance o Air trapping o Decreased compliance o Increased work of breathing

Ventilation / perfusion mismatching o Hypoxemia

Paradoxical breathing o Decreased tidal volume o Decreased minute ventilation

Path: large mucus plug, fairly loose, some cellularity Related to CERTAIN INFECTIONS

RSV: causes lower airway dz in infants (cold in adults)

Also: influenza A, metapnuemo, paraflu, adenovirus, mycoplasma pneumonia Clinical manifestations of RSV:

Rhinorrhea

Cough

Low grade fever

Apnea (CNS-related) o Early: RSV-specific o Later: sign of resp failure

Tachypnea

Hypoxemia

Wheezes / Crackles

Therapy:SUPPORTIVE CARE

Remember: not all that wheezes is asthma… but most of it is

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Upper Airway Disorders

Anatomy Review Nasal Cavity Turbinates and sinus ostia (ethmoid, maxillary, frontal)

Nasopharynx Airway posterior to the nasal passages, adjacent to soft palate

Oropharynx Posterior to the tongue

Hypopharynx Superior to and including the vocal cords

Larynx Airway inferior to the vocal cords

Where are potential sites of obstruction?

Upper Airway Development Birth: large epiglottis

covers soft palate, forming channel that encourages nasal breathing

INFANTS are OBLIGATE NASAL BREATHERS o If you block the nose, hard to breathe! o Cleaning out the nose (congestion) helps with many problems

If epiglottis closed, straight shot to esophagus: o but everything close to each other: easy to aspirate!

Laryngeal Position

Infants: have high larynx (C3) o more efficient breathing with nursing o ↓ aspiration risk

Adults: larynx drops down (C5) o Better for speech (longer passage) o Older, better coordination, can handle aspiration risk

Neanderthals were somewhere in between (some capacity for speech)

Airway Obstructions: Overview Nasopharyngeal obstruction Oropharyngeal obstruction Laryngopharyngeal obstruction Infection

Choanal atresia

Adenoid hypertrophy

Tonsillar hypertrophy

Micrognathia

Macroglossia

Laryngomalacia

Vocal cord paralysis

Subglottic stenosis

Croup

Epiglottitis

Diphtheria

Nasopharyngeal Obstruction

Choanal atresia Nasal cavities extend poteriorly during development, directed by palatal process’ fusion

Membrane separates nasal cavitiy from oral cavity thins & ruptures (mid 1st

trimester)

Rupture failure = choanal atresia o Remember infants are nasal breathers: 1° route of breathing obstructed

Epidemiology: most common cause of true nasal obstruction (1:10k)

2:1 unilateral:bilateral Associated with other congenital anomalies in 50%, including CHARGE

Colomba, heart, choanal atresia, retarded growth, genital hypoplasia, ear defects

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Choanal atresia, cont.

Presentation: can cause cardirespiratory failure on 1st day after birth

Apnea, cyanosis, respiratory distress – relieved with crying / mouth breathing o Re-establishing an airflow via mouth!

Dx: try to pass a #8 French catheter through each nostril to see if it’s patent!

Complications:

Aspiration from dyscoordination (2° to ↑ nasal airway resistance)

Severe hypoxemia with sleep (trying to breathe through nose obstructive apnea) Treatment: INTUBATION is most effective initial treatment

Surgical excision with stent (4+ wks) to prevent recurrence is definitive

Waldeyer’s Ring “adenoids & tonsils”

Pharyngeal tonsils = adenoids

Lingual tonsils too

Palatine tonsils = normal tonsils

Tubal tonsils – back side Tonsils have strategic placement

Where particles should drop out of air

Lymphoid tissue picks it up But if they get inflamed, they can cause instruction

Adenoid Hypertrophy Long face

Open mouth breathing (blocked nasal passage)

“Nasal” voice

↓ development of maxilla over time Maxillary development is dependent on nasal breathing

Some weird oxygenation effect?

Chronic obstruction ↓ maxillary growth Treatment: adenoidectomy

Oropharyngeal Obstruction

Tonsilar hypertrophy “kissing tonsils” – see pictures

Can be graded but airway obstruction doesn’t correlate directly o Also depends on airway tone is with sleep!

Cause airway obstruction

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Presentation (Tonsilar hypertrophy)

Snoring is most common Muffled voice, drooling, trouble swallowing, choking on solids (more rare)

Obstructive sleep apnea: no airflow movement during breathing (dx with sleep study) o mostly between 2-6 years old (tonsils growing, airway smaller) o or adolescents (heavier more soft tissue)

Treatment: Tonsillectomy (80-90% successful)

Micrognathia often associated with underlying genetic disorders

Pathophysiology: Mandibular hypoplasia of unclear etiology

often associated with cleft palate o (small jaw tongue displaced ↑ palate shelves can’t fuse)

Therapy:

Mild micrognathia: may improve by school age

Severe micrognathia: can require intubation / tracheostomy

Better breathing in prone position (tongue flops forward out of airway)

Mandibular distraction mandibular remodeling (pic)

Labiolingual suturing (“tongue-lip adhesion”) o prevents tongue from being posteriorly displaced o temporary (until child grows)

Macroglossia Big tongue

Associated with: angioedema, congenital syndromes (e.g. Beckwith-Wiedemann), lymphangioma

Pathophysiology: Tongue displaced into hypopharynx obstructive apnea

Therapy: prone positioning, tongue debulking (rarely done)

Laryngopharyngeal obstruction

Laryngomalacia Most common cause of stridor in infants

o Inspiratory noise, implies extrathoracic obstruction o (Wheezing = expiratory, intrathoracic – e.g. asthma)

Pathophysiology:

Dynamic anomaly, cartilage collapses into airway

Etiology unclear (no tissue anomalies, no differences in muscle bulk – maybe muscle dyscoordination, structural variation) Presentation:

Stridor onset since birth, minimal respiratory distress

Worse in supine position and when agitated / active

↓ noise when at rest (↑ flow ↑ turbulence – kind of like cardiac murmurs)

Normal voice quality & pitch Treatment: usually no therapy required (resolves by 12 mo)

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Vocal Cord Paralysis #2 common congenital laryngeal abnormality

Bilateral VCP Unilateral VCP

Etiology usually idiopathic

can be from CNS lesions (anything pressing on brainstem

usually recurrent laryngeal nerve damage

birth trauma or with cardiac surgery too (e.g. PDA ligation)

Presentation Diagnosed late

Mild stridor, hoarse phonation, occasional aspiration

Normal phonation & stridor

Occasionally as airway emergency (if on top of cough, cold, etc)

Treatment Correct CNS lesions, may need tracheostomy Improves (↓ inflammation, other VC compensates)

Signs of birth trauma: think VCP possibly

VCP: can be early sign of brain stem / spinal cord compression

Acquired too: local neck trauma, head trauma, viral compression (more rare in kids)

Subglottic Stenosis Congenital Acquired

Epidemiology 3rd most common laryngeal anomaly Related to airway inflammation

Pathophysiology Incomplete recanalization of larynx during gestation

Inflammatory factors: prolonged intubation, traumatic

intubation, oversized endotracheal tube used, GE reflux Presentation Recurrent / persistent croup Hx of prior intubation, airway instrumentation

If Severe stenosis: biphasic stridor, dyspnea, labored breathing

Gets much worse if they have a cough or cold already obstructed If you’re having trouble with expected ET tube size, be careful! Treatment: frequently requires tracheostomy or airway surgery (more than other two)

Laryngopharyngeal Obstructions: Approach Diagnosis:

X-rays correlate poorly with actual degree of airway narrowing

Flexible laryngoscopy for Dx

Pulmonary function tests upper airway obstruction (need > 6yo kid) Laryngoscopy: looking down into the airway

Laryngomalacia

Epiglottis somewhat omega-shaped Can see that it’s dynamic (collapsed on picture to right)

Vocal cord paralysis

Unilateral vocal cord paralysis (lack of bulk on paralyzed side in L picture, doesn’t completely close in R picture) Opening: should close completely (aspiration risk)

Subglottic stenosis

Very narrow opening (all subglottic stenosis closing it up)

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Laryngopharyngeal Obstructions: Complication Inability to coordinate feeding

Growth failure, aspiration

Treatment: occupational therapy or feeding tube (worst-case scenario) Obstructive apnea (GET A SLEEP STUDY)

Hypoxemia growth failure, neurodevelopmental delay, pulmonary HTN & cor pulmonale o Sleep study for snoring kids!

Treatment: CPAP / BiPAP (stent open airway), airway surgery and/or tracheostomy

Infections

Viral Croup (Laryngotracheobronchitis) Most common infectious cause of upper airway obstruction in pediatrics

o Peak 18-24 mo o Often post-URTI (coryzal prodrome)

Most common agents (75% cases): parainfluenza viruses (esp. PIV1) Pathophysiology:

Edema narrowing; stridor from turbulence

Smaller airway, poor cell-mediated immunity predisposition of airway obstruction

Cricoid cartilage: complete ring (not C-shaped like lower down in trachea, bronchi) o Bigger reduction in lumen (so more predisposition to obstruction) (resistance ↑ with r4)

Presentation:

Barking cough, hoarse voice, inspiratory stridor (exertion / agitation), restlessness o Drooling / resp distress in severe cases

Symptoms worse at night

Hypoxemia / hypercarbia: severe upper airway obstruction

Hx of recurrent croup suggests underlying abnormality (more than 3-4x in same kid)

X-ray: STEEPLE SIGN is classic

Supposed to be open airway but blocked!

Doesn’t correlate with severity of obstruction Therapy:

Nebulized epinephrine (α-adrenergic effects vasoconstriction, ↓ edema) o beta-agonists don’t help o Doesn’t affect duration of croup

o REBOUND can occur – keep watching the kid for a while! Heliox mixtures ↓ turbulence but no large studies

Most studies: no benefit with humidified air

Corticosteriods: supported by evidence but type, route, dosing regimen debated

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Epiglottitis Cellulitis of supraglottic structures

Typically 2-7 yo in autumn / winter

Incidence ↓↓ with HiB vax

Pathophysiology of Epiglottitis

HiB 99% of cases historically o Other bacteria & some viruses since vaccine o HiB still in non-immunized, vaccine failure

(trisomy 21, prematurity, malignancy, immunodeficiency)

Presentation

Rapid for HiB, more gradual for strep Sore throat / dyspnea muffled voice, drooling, tripod position, toxic appearance

o Picture: kid tripoding (leaning forward, on hands; retractions too) Stridor isn’t prominent but can occur with worsening obstruction

X-ray: THUMB SIGN

(looks like large thumb on epiglottis - inflammation)

Getting X-rays before airway secured = controversial Therapy: MEDICAL EMERGENCY

Call ENT or anesthesia IMMEDIATELY

Inhalational induction of anesthesia, intubation:

but be ready to do tracheostomy

Abx: cover HiB & Strep

Some evidence for empiric use of steroids Prognosis: Intubation time: 1.3 days for HiB, 6d for Strep

Diptheria Incidence ↓↓↓ with vaccination

Exudative material clogs / blocks airway (gray films)

Antitoxin is mainstay of therapy

Important Points

Upper airway obstruction can present as a medical emergency Secure the airway first, then worry about diagnoses

Nasal obstruction can pose significant problems for obligate nasal breathers (infants)

Obtain polysomnography (sleep study) to assess severity of obstructive apnea Pulse-oximetry alone is not adequate

Asymptomatic examination while awake can be misleading

Why we treat: Obstructive apnea can lead to growth failure, developmental delays, and right ventricular failure