Definition: TLC decreased by 20% compared to predictedvalues based on height, age, gender

RESTRICTIVE DISEASES OF THE LUNG

Vol

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(L)

0

time (seconds)

FRC TLC

RV

VC

VT

Fig. 13.16

Pressure

Volume

Fluid filled lung Air filled lung Air filled lungwithout surfactant

water molecule

surfactant molecule

Pressure

Volume

Full term

Preemie

Lung Pressure Volume Curves

PULMONARY EDEMA

Pulmonary edema

CAUSES OF PULMONARY EDEMA

1. Cardiogenic• Myocardial infarction• Hypertensive left heart failure

2. Increased capillary permeability• Inhaled or circulating toxins

• Endotoxin• High O2 over long periods of time• Radiation• SO2, NO2

• Bacterial and viral pathogens

left atrial pressure

pressure in pulmonary vein

Pcap

fluid flux across the endothelium

Cardiogenic pulmonary edema

Usually self correcting:•increased fluid flux increases PIF

•increased fluid flux concentrates proteins in capillaries, increasing cap

Increased capillary permeability

Inflammation

Increased permeability of pulmonary capillaries

Increased protein leak across capillaries

↓ cap

↑ fluid flux across capillaries

Usually not self limiting•fluid that leaks out has protein in it, increasing the oncotic pressure of the interstitial spaces

Symptoms

•dyspnea•cough (particularly in the recumbent position)•the cough is often non-productive in the early stages, but in the advanced stages, it may bring up pink foam,and cyanosis may be present

Pulmonary Function

•the PV curve of the lung is shifted downward and to the right•resistance to flow through airways may increase -(fluid forms around airways and isolates them from retractive forces

of the lung parenchyma)•TLC, VC, FRC decrease

How does edema affect lung compliance?

Air Air

“Good” lung“Good” lung

Air Air

“Good” lung“Good” lung

Breath goes evenly to both lungs

Compliance = V/ P

Fluid andpus

Air

“Good” lung“Bad” lung(very stiff)

Breath only goes to good lung

Compliance = V/ P 2

Gas Exchange

If only interstitial edema is present•little change in blood gases

If alveolar edema is present•decreased PaO2 (due to shunt)•PaCO2 normal or even low (hyperventilation).•Reason for hyperventilation:

•low PaO2

•stimulation of lung receptors by high transpulmonary pressures (lung is stiffer, so it requires greater pressures for ventilation)

Pulmonary alveolar proteinosis

Lavage Number

1 2 3 4 5 6 7 8 9 10

Proteinaceous material filling the alveoli, but no inflammatory cells

OBESITY AND THE LUNG

systemicinflammation

mechanicalunloading

adipocytederived hormones

FRC

VT

leptin

adiponectin

PAI-1

lungdevelopment

systemicinflammation

mechanicalunloading

adipocytederived hormones

FRC

VT

leptin

adiponectin

PAI-1

lungdevelopment

systemicinflammation

mechanicalunloading

adipocytederived hormones

FRC

VT

leptin

adiponectin

PAI-1

lungdevelopment

How does obesity impact:

1. Pulmonary mechanics

2. Pattern of breathing

3. Blood gases

4. Pulmonary Disease

How does obesity impact:

1) Pulmonary mechanics• Lung volumes• Airway caliber• Airway responsiveness

2) Pattern of breathing

3) Blood gases

4) Pulmonary disease

How does obesity impact:

1) Pulmonary mechanics• Lung volumes• Airway caliber• Airway responsiveness

2) Pattern of breathing

3) Blood gases

4) Pulmonary disease

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0

time (seconds)

FRC TLC

RV

VC

VT

www.lib.mcg.edu/.../4ch2/4ch2ques/4q2pg9.htm

www.lib.mcg.edu/.../4ch2/4ch2ques/4q2pg9.htm

Obesity makes thechest wall stiffer

Obese FRC

Chest wall in obesity

Lean FRC

Lean Obese

FRC

TLC

ERV

RV

Adapted From: Rubinstein et al Ann Intern Med 112:828-832, 1990.

(293 subjects)

RV airway closure

VC

How does obesity impact:

1) Pulmonary mechanics• Lung volumes• Airway caliber• Airway responsiveness

2) Pattern of breathing

3) Blood gases

4) Pulmonary disease

Lung Volume

Air

way

Res

ista

nce

What is the status of the airways in the obese subject?

From: King et al: Eur. Respir. J. 25:896-901, 2005

Gaw is corrected for absolute lung volume Gaw = 1/Raw

The airways of obese subjects are narrowed. The airwaynarrowing is more than could be expected on the basis of reduced lungvolume alone.

Interim conclusion

What else is causing airway narrowing?

From: Tilg and Moschen Nat Rev Immunol 6(10):772-783, 2006

FACTORS PRODUCED BY ADIPOSE TISSUE

CYTOKINESTNFIL-6IL-1

PBEFTGFIL-10

CHEMOKINESIL-8

EotaxinMCP-1MIP-1

ENERGY REGULATING HORMONES

LeptinAdiponectin

Resistin

ACUTE PHASE REACTANTSSerum amyloid AC-reactive protein

PAI-11-acid glycoprotein

OTHER FACTORSAngiotensinogen

Complement B, C3, DAcylation-stimulating protein

VEGFIL-1RA

Retinol-binding protein-4

How does obesity impact:

1) Pulmonary mechanics• Lung volumes• Airway caliber• Airway responsiveness

2) Pattern of breathing

3) Blood gases

4) Pulmonary disease

From Litonjua et al Thorax 57:581-585, 2002

Weight gain increases the likelihood of developing AHR

How does obesity impact:

1) Pulmonary mechanics

2) Pattern of breathing

3) Blood gases

4) Pulmonary disease

Adapted from Sampson and Grassino, J. Appl. Physiol. 55:1269-1276, 1983.

Obesity leads to decreased tidal volume and increased frequency

How does obesity impact:

1) Pulmonary mechanics

2) Pattern of breathing

3) Blood gases

4) Pulmonary disease

work to move larger body weight

CO2 production

Most obese increase VE to maintain normal PaCO2

What about PaO2?

Lean Obese

FRC

TLC

ERV

RV

Adapted From: Rubinstein et al Ann Intern Med 112:828-832, 1990.

(293 subjects)

RV airway closure

VC

“Airway closure occurred within a tidal breath in 9 out of 10 (obese) subjects during spontaneous breathing”

“PaO2 correlated with the magnitude of airway closure”

Acta Anesthesiol Scand 20:334-42, 1976.

Airway closure

Shunt

↓PaO2

How does obesity impact:

1) Pulmonary mechanics

2) Pattern of breathing

3) Blood gases

4) Pulmonary disease

Obesity and Pulmonary Disease

•Asthma

•COPD

•Obstructive Sleep Apnea

•Obesity Hypoventilation Syndrome

•Pulmonary Hypertension

From: Nystad et al, Am J Epidemiol 160:969-976, 2004

Obesity increases the risk of incident asthma

Obesity and Pulmonary Disease

•Asthma

•COPD

•Obstructive Sleep Apnea

•Obesity Hypoventilation Syndrome

•Pulmonary Hypertension

Obesity and COPD

From: Guerra et al, Chest 122:1256 - 1263 , 2002

Issues: lack of exercise, lifestyle factors

Obesity and Pulmonary Disease

•Asthma

•COPD

•Obstructive Sleep Apnea

•Obesity Hypoventilation Syndrome

•Pulmonary Hypertension

Obesity and Obstructive Sleep Apnea

www.focusonhealthyaging.com/.../sleep_apnia.gif

Sleep

muscles relax

tongue and soft palate fall against back of throat

obstruction

hypoxemia

arousal

Obstruction can occur 5-50 times per hour!

Outcomes:

•Loss of sleep•Excessive daytime sleepiness•Headaches upon awakening•Depression•Hypertension•Cardiovascular disease•Stroke

sleephelpusa.com/images/brewster-ginger.jpg

Obesity

Fat deposition in soft palate, uvula, neck area, pharynx

Increased risk of obstruction

Obesity and Pulmonary Disease

•Asthma

•COPD

•Obstructive Sleep Apnea

•Obesity Hypoventilation Syndrome

•Pulmonary Hypertension

Obesity Hypoventilation Syndrome (Pickwickian syndrome)

•Arterial hypercapnia (increased PaCO2) while awake•Hypersomnolence•Fatigue•Morning headaches•Hypoxemia•Polycythemia•Pulmonary hypertension•Right ventricular failure

Cause?

Sleep disordered breathing combined with chronic hypoxemia andhypercapnia leading to blunting of chemoreceptor responsiveness

Obesity and Pulmonary Disease

•Asthma

•COPD

•Obstructive Sleep Apnea

•Obesity Hypoventilation Syndrome

•Pulmonary Hypertension

Low PAO2 leads to constriction of pulmonary arterioles

“96% of obese subjects living at altitude have pulmonary hypertension”

Valencia-Flores et al Int. J. Obesity 28:1174-1180, 2004

Normal

Airway Edema