Pulmonary Pathophysiology

N230B: Advanced Pathophysiology.
The
CF
Foundations
Mission
Advanced Nurse Practice Program.
UCLA School of Nursing. October 21, 2015.
Mechanisms of
Pulmonary Disease
Thomas G. Keens, M.D.
Professor of Pediatrics, Physiology and Biophysics,
Keck School of Medicine of the University of Southern California.
Division of Pediatric Pulmonology and Sleep Medicine,
Childrens Hospital Los Angeles.
E-mail:
No Conflicts of Interest to Disclose

Respiratory
Physiology and
Pathophysiology
Normal Lung
Function
The maintenance
of normal arterial
oxygen tension
(Po2), carbon
dioxide tension
(Pco2), and pH,
without excessive
cardiac or
pulmonary work.
Adequate Gas Exchange
Adequate
Ventilation.
Adequate
Perfusion.
Distribution of
Ventilation.
Diffusion of O
Comroe, J.H., et al. The Lung. Year Book
Medical Publishers, Chicago, 1962.
and
CO2 across the

alveolar-capillary
membrane.
Adequate Gas Exchange
Non-uniform
Comroe, J.H., et al. The Lung. Year Book

Medical Publishers, Chicago, 1962.
distribution of
ventilation is
the most
important
cause of gas
exchange
abnormalities
in human lung
disease.
Structure of
the Lungs
Airways:
23 generations.
0-16: conducting
airways.
17-23: respiratory
bronchioles.
Alveoli:
300-500 million
Netter, F.H. Respiratory System. Volume 7, CIBA

Collection of Medical Illustrations. 1979.
alveoli.
Gas exchange
surface.
Berne, R.M., and M.N. Levy. Principles of Physiology. Mosby, St. Louis, 2000.
Alveoli
Site of most gas exchange.

Adults have 300-500 million
alveoli.
and CO2 exchange is by

diffusion across the alveolar
capillary membrane.
2
Thin membrane 0.5-1.0 m thick.

Tisi, G.M. Pulmonary Physiology in Clinical Medicine. Williams and Wilkins, Baltimore, 1980.
USC
UCLA
Alveolar Surface Area

of Adult Lungs
Alveolar surface area of adult lungs = 75 M2 = 90 square

yards. (1.7% [1/60th] the area of a college football field).
Comroe, J.H., et al. The Lung. Year Book Medical Publishers, Chicago, 1962.
Compensation for
Regional Hypoxia
One can not correct regional

Po2 by V/Q in another
lung region.
Thus, Po
is the most
sensitive index of the
presence of lung disease.
One can Po2 by O2

entering the hypoxic region,
by FIo2.
Typesof
of Respiratory
Respiratory Dead
Types
DeadSpace
Space
Conducting
Airways
Alveoli with
No Bloodflow
Causes of Hypoxemia
Diffusion defect.
Hypoventilation.
Decreased V/Q.
Right-to-Left shunt.
Causes of Hypercapnia
Hypoventilation.
Decreased V/Q.
Distribution of Ventilation
Decreased
Compliance
Airway
Obstruction
Pulmonary Mechanics
Compliance.
Volume
Compliance =
Pressure
Resistance.
Pressure
Resistance =
Flow
Pulmonary
Compliance (CL)
of the line is
Slope
compliance.
Volume
CL =
Pressure
pressure The
volume curve of the
Tisi, G.M. Pulmonary Physiology in Clinical Medicine.

Williams and Wilkins, Baltimore, 1980.
lung is not a line,

but a loop.
Referred to as
hysteresis.
Volume
CL =
Pressure
Pressure
Resistance =
Flow
Extrathoracic Upper Airway Obstruction
Intra Pulmonary Airway Obstruction
Pressure Acting
on Airways
Sasaki, H., et al. J. Appl. Physiol., 45: 858-869, 1978.
Airway Obstruction
Cherniack, R.M., et al. Respiration in Health and Disease. W.B. Saunders, Philadelphia, 1972.
Hyperinflation
Atelectasis
Airway Obstruction
Increased airway resistance.
Bronchospasm.
Airway Inflammation.
Mucous plugging.
Extrinsic compression of the airway.
Foreign body in the airway.
Decreased Elastic Recoil.
Emphysema.
Airway Inflammation
Causes airway
obstruction by:
Mucous plugging.
Increased mucous
Mucosal edema.
secretions.
Bronchospasm.
Common in:
Asthma.
Chronic
bronchitis.
Cystic
Fibrosis.
Airway Obstruction
Emphysema
Netter, F.H. Respiratory System. Volume 7, CIBA Collection of Medical Illustrations. 1979.
Lung
Apex
Lung
Base
Rest
Exercise

Pulmonary
Disorders
Pulmonary Disorders
Pneumonia.
Aspiration
pneumonia.
Influenza pneumonia.
Tuberculosis.
Pulmonary fibrosis.
Bronchiolitis.
Asthma.
Chronic bronchitis.
Emphysema.
Bronchiectasis.
Cystic fibrosis.
Pneumothorax.
Pulmonary edema.
Pulmonary
embolus.
Pneumonia
Infection of the lung.
Requires treatment
of the infection with
antibiotics.
Alveoli are filled with

infected material.
Systemic
antibiotics are
usually required.
Pneumonia
Infection may also

cause:
Bronchospasm
requiring
bronchodilators.
pulmonary
capillary
permeability
causing edema.
Normal Chest X-ray
Pneumonia
Pneumonia
Radiographic Patterns
of Lobar Infiltrates
RUL
LUL
RML
LLL
RLL
Pneumonia Caveats
Recurrent pneumonias are not normal.
Consider underlying disorders which might
predispose the patient to >2 pneumonias:
Chronic Lung Disease.
Recurrent aspiration.
Untreated asthma.
Cystic Fibrosis.
Abnormal mucociliary clearance, host
defenses, or immune deficiency,
Congenital malformations.
Aspiration
Pneumonia
Aspiration occurs
most commonly in
patients with
swallowing
dysfunction.
Elderly.
Neurologically
impaired.
Seizures.
GERD.
Aspiration Pneumonia
RML is the most common site.
1918 Influenza pandemic killed as

many as 50,000,000 people world-
Influenza Virus
Influenza Pneumonia
Influenza
Pneumonia
Annual outbreaks
in winter.
High fever, muscle

aches.
Pneumonia is the
usual cause of
death.
Antiviral agents
only partly
effective.
Tuberculosis
2,000,000 deaths per
year worldwide.
One-third of worlds
population infected.
>8,000,000 new
cases diagnosed
each year.
Multiple drug
resistant TB
emerging as a
worldwide public
health threat.
Tuberculosis (Gohn complex)
Tuberculosis (Gohn complex)
Tuberculosis
Miliary Tuberculosis
Tuberculosis: Caseating Granuloma
Tuberculosis Cavitary Lung Disease
Tuberculosis Cavitary Lung Disease
Tuberculin
Test
Tuberculin Skin
Skin Test
Diagnoses TB infection.
Positive 2-12 weeks after
infection.
Criteria for positive TST.

Induration Population (Risk)
American Academy of Pediatrics.

The Red Book. 2006.
5 mm
Immunocompromised
Contact with TB
patient.
10 mm
Risk of dissemination.
Increased exposure to
TB disease.
15 mm
No risk factors.
Tuberculin Skin Test
Diagnoses TB infection.
Positive 2-12 weeks after
infection.
Criteria for positive TST.

Induration Population (Risk)
American Academy of Pediatrics.

The Red Book. 2006.
5 mm
Immunocompromised
Contact with TB
patient.
10 mm
Risk of dissemination.
Increased exposure to
TB disease.
15 mm
No risk factors.
Interstitial Pneumonitis
and Fibrosis
If untreated, interstitial
pneumonitis progresses to
fibrosis, destroying alveolar
tissue and blood vessels
lung volumes and CL.
Patients have shortness of

breath, tachypnea, and
exercise tolerance.
May result from many types

of lung injury.
Digital Clubbing
Commonly seen in chronic lung diseases

associated with hypoxia and/or inflammation.
Pulmonary Fibrosis
Pulmonary Fibrosis
Normal Chest CT Scan
Pulmonary Fibrosis
Pulmonary Fibrosis
Interstitial Pneumonitis
and Fibrosis
Restrictive lung disease.

Treatment is that of the
underlying cause.
High dose systemic
corticosteroids suppress
active inflammation.
Other chronic medications:
Azathioprine.
Cyclophosphamide.
Hydroxychloraquine.
Bronchiolitis
Acute, life-threatening
disorder in infants.
Infectious
inflammation of
bronchioles 75-300 in
diameter.
Respiratory syncytial
virus (RSV).
Hypoxia, airway
obstruction, and
hyperinflation.
Bronchiolitis
Asthma
Most common chronic lung

disease.
15% of U.S. children.
Inhalation is the route of choice

for the administration of
medications, as it is associated
with the least side effects.
Characterized by episodes of
airway narrowing resulting from
bronchospasm and
inflammation.
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma, 2007.
Inflammation
Airway mucosal inflammation
causes swelling of the airway
lining and mucous secretion.
Release of inflammatory
mediators.
Cytokines.
Leukotrienes.
Primary target to control asthma
symptoms.
Nebulizers
Metered Dose Inhalers
Chronic Bronchitis
Chronic infection and
inflammation of the
bronchi and bronchioles.
Narrowing of airways due

to bronchospasm,
inflammation, and
infection.
Bronchiectasis: airways
lose cartilaginous
support; collect infectious
materials.
Netter, F.H.
Respiratory
System. Volume
7, CIBA Collection
of Medical
Illustrations.
1979.
Chronic Bronchitis
(Blue Bloater)
Chronic Bronchitis
Treatment.
Bronchodilators to treat
bronchospasm.
Inhaled corticosteroids to
treat inflammation.
Antibiotics to treat
infection.
Supplemental O2 to treat
hypoxia.
Emphysema
Destruction of alveolar
walls.
Decreased surface area

available for gas
exchange.
Decreased elastic
support of airways.
Airway obstruction.
Severe hyperinflation
often present.
Chest x-ray of Emphysema (Pink Puffer)
Airway Obstruction in
Emphysema (Pel)
Emphysema
Treatment.
Bronchodilators to reverse
bronchospasm.
Corticosteroids for
inflammation.
Antibiotics to treat infection.
Diuretics and digitalis to
treat right heart failure (cor
pulmonale).
A 12-year old boy

was chewing on his
pencil eraser tip.
He accidentally
swallowed it.
He coughed for
2-months.
Did he really
swallow the eraser
tip?
Retained Foreign Body

Aspiration
Foreign body puts pressure on airway mucosa;

compromises bloodflow, and destroys airways.
Chronic infection sets in, causing further airway

destruction.
Bronchiectasis
Abnormal dilatation of
bronchi.
Involves destruction of
cartilaginous walls.
Most commonly due to

chronic infection.
Can be focal or diffuse.

Always due to an
underlying lung disease.
Bronchiectasis
Bronchiectasis
Common in chronic lung

diseases.
Cystic Fibrosis.
Primary ciliary dyskinesia.
Immune deficiencies.
Tuberculosis.
Chronic infection destroys

cartilaginous airways.
Obstructive lung disease.

Risk of massive
hemoptysis.
Woe the child who

tastes salty from
a kiss on the brow,
for he is hexed,
and soon must die.
--- Medieval German Folk Saying
Cystic Fibrosis
Most common inherited

serious exocrine
disorder in Caucasians.
Autosomal recessive.
Most serious clinical

problem and most
common cause of death
is CF lung disease.
Multiple systems
involved.
Discovery of the
Cystic Fibrosis
gene in 1989.
Cystic Fibrosis
Transmembrane
Conductance
Regulator
(CFTR) Protein.
Chloride
channel in
exocrine cells.
Rommens, J.M., et al.

Science, 245: 1059-1080, 1989.
Normal
CF
Na+
Cl-
ASL
H2O
ASL
Na+
H2O
H2O
H2O
H2O
Matsui, H., et al. Cell, 95: 1005-1015, 1998.
CF Bronchiectasis
CF Bronchiectasis
CF Bronchiectasis
CF
Cystic Fibrosis
Cystic Fibrosis
Home Pulmonary Therapy
Median Survival for CF Improves

50
40
Age (years)
30
20
10
0
1940 1950 1960 1970 1980 1990 2000 2010 2020
Pneumothorax
Pneumothorax can arise from

ruptured bullae or blebs.
Pneumothorax
Pneumothorax
Pneumothorax in an Infant
Tension Pneumothorax
Fluid Exchange in
Pulmonary Capillaries
The alveolar-capillary
membrane is porous.
Fluid exchange can

occur across the
membrane.
In the lung, fluid
should remain in the

capillary, not in the
alveolus.
What forces keep fluid

in pulmonary
capillaries?
Tisi, G.M. Pulmonary Physiology in Clinical

Medicine. Williams and Wilkins, Baltimore, 1980.
Fluid Exchange in
Capillary
Colloid
osmotic
pressure.
Alveolar
pressure.
Alveolus
Capillary
hydrostatic
pressure.
Alveolar
surface
tension.
Fluid Exchange in
capillary
hydrostatic
pressure pushes
fluid into alveoli,
causing pulmonary
edema.
capillary

hydrostatic
pressure pushes
fluid into interstitial
space, causing stiff
lungs.
Pulmonary Lymphatics
Fluid is cleared
from the interstitial

space by
lymphatics.
Pulmonary
lymphatics drain
through the hilum
to the thoracic duct
in the superior
vena cava.
Netter, F.H. Respiratory System. Volume 7, CIBA

Collection of Medical Illustrations. 1979.
Heart Failure and

Pulmonary Edema
Left Heart Failure.
Blood backs up from the

left ventricle into the
lungs.
Increases capillary
pressure.
Right Heart Failure.

Blood backs up from

the right ventricle into
systemic veins.
Thoracic duct flow.
Pulmonary fluid
clearance.
Pulmonary Embolism
Clot travels from venous

system to the lungs.
Can cause infarction of a

portion of lung.
Massive PE can occlude
most or all of pulmonary

outflow tract.
Can cause Right Heart

Failure.
Can cause sudden death.
Requires prompt diagnosis

and treatment.
Pulmonary Embolism
Deep venous thrombosis in
femoral veins is a common cause.
Other risk factors are
immobilization of legs for

prolonged periods.
Signs and Symptoms:

Cough.
Chest pain.
Dyspnea.
Hypoxia.
Treatment is anticoagulation.
Lung Response to Injury

Although we have reviewed a
number of specific lung
diseases, the lung has only a
few ways to respond to
injury.
Inflammation.
Airway obstruction,
remodeling, and
bronchiectasis.
Fibrosis.
Loss of alveoli.
Repair (return to normal
Why the Respiratory System is

the most important organ system
To know even
one life has
breathed easier
because you
have lived - that
is to have
succeeded.
Ralph Waldo Emerson
1803-1882

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N230B: Advanced Pathophysiology.

No Conflicts of Interest to Disclose

N230B: Advanced Pathophysiology.

Adequate Gas Exchange

CO2 across the

Adequate Gas Exchange

Comroe, J.H., et al. The Lung. Year Book

Netter, F.H. Respiratory System. Volume 7, CIBA

Site of most gas exchange.

and CO2 exchange is by

Thin membrane 0.5-1.0 m thick.

Alveolar Surface Area

Alveolar surface area of adult lungs = 75 M2 = 90 square

One can not correct regional

One can Po2 by O2

Tisi, G.M. Pulmonary Physiology in Clinical Medicine.

lung is not a line,

Extrathoracic Upper Airway Obstruction

Intra Pulmonary Airway Obstruction

Sasaki, H., et al. J. Appl. Physiol., 45: 858-869, 1978.

Increased airway resistance.

Decreased Elastic Recoil.

N230B: Advanced Pathophysiology.

Infection of the lung.

Alveoli are filled with

Infection may also

Normal Chest X-ray

RML is the most common site.

1918 Influenza pandemic killed as

High fever, muscle

Tuberculosis (Gohn complex)

Tuberculosis (Gohn complex)

Tuberculosis: Caseating Granuloma

Tuberculosis Cavitary Lung Disease

Tuberculosis Cavitary Lung Disease

Criteria for positive TST.

American Academy of Pediatrics.

Tuberculin Skin Test

Criteria for positive TST.

American Academy of Pediatrics.

Patients have shortness of

May result from many types

Commonly seen in chronic lung diseases

Normal Chest CT Scan

Restrictive lung disease.

Most common chronic lung

15% of U.S. children.

Inhalation is the route of choice

Metered Dose Inhalers

Narrowing of airways due

Decreased surface area

Chest x-ray of Emphysema (Pink Puffer)

A 12-year old boy

Retained Foreign Body

Foreign body puts pressure on airway mucosa;

Chronic infection sets in, causing further airway

Most commonly due to

Can be focal or diffuse.

underlying lung disease.

Common in chronic lung

Chronic infection destroys

Obstructive lung disease.

Woe the child who

Most common inherited