Download Panlobular Emphysema

COPD
(Definitions + Pathology)
Dr.Mohsen SHAHEEN
Pneumologist
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COPD
High
Morbidity
Mortality
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A common respiratory disease
Chronic Inflammation
Small + Large Airways
Fixed Airflow Limitation
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COPD affects more than
the population
5% of
It is the third-ranked cause of death in
the US
Killing more than 120,000 individuals
each year
COPD
is a High Chronic
and
Prevalence Disease
The impact of COPD
High Medical resource
utilization
Frequent clinician
office visits
The impact of COPD
Frequent
hospitalization
s due to
acute
exacerbations
The impact of COPD
Need for chronic therapy
Supplemental
oxygen
therapy
Medications
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 Symptoms (especially dyspnea)
Frequency and severity of
exacerbations
 Health status
 Exercise capacity
 Prolong survival
Definition of COPD
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common Preventable
and treatable disease
Non
Curable
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Exposure  Toxic particles + Gazes
Chronic Inflammation
S m a l l + L a rge a i r way s
Lung
Progressive airflow limitation
Chronic Bronchitis
Emphysema
Chronic Bronchitis
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Chronic
Productive
Cough
For 3 months in each of
two successive years
In a patient in whom other causes of
chronic cough (eg, bronchiectasis)
have been excluded
Emphysema
Conducting Zone
Trachea
Primary Bronchus
(BR)
Bronchioles (BL)
Terminal bronchioles
(TBL)
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Source: From Weibel 360
Respiratory Zone
 Respiratory
bronchioles (RBL)
 Alveolar ducts (AD)
 Alveolar sacs (AS)
 Alveoli (300 million)
Definition of Emphysema
Abnormal and permanent Enlargement of
the airspaces distal to the terminal
bronchioles
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Destruction of the airspace walls
without obvious fibrosis
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Types of Emphysema
1. Pure emphysema
2. Emphysema + Mild Fibrosis
3. Interstitial Pneumonias +
Emphysema
4. Emphysema  Moderate or
severe airflow obstruction
( more common)
5. Emphysema + Normal pulmonary
Function
Pathology of COPD
Airways
Pathology
COPD
Lung
parenchyma
Pulmonary
vasculature
COPD Is a Disease Characterized
by Inflammation
Cigarette smoke
Epithelial
cells
Macrophage/Dendritic cell
Neutrophil
Monocyte
Fibroblast
CD8+ Tc cell
Proteases
Fibrosis
Obstructive bronchiolitis
Emphysema
Mucus hypersecretion
Airway inflammation in COPD
Neutrophilic inflammation
 Numbers of Macrophages
CD8+ T-lymphocytes
Neutrophilic inflammation
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Neutrophils
Key effector cells in COPD
Increasing cell
numbers correlate
with declining lung
function
Neutrophils
Infiltrating
Bronchial Glands
in COPD
Release mediators
involved in
neutrophil,
monocyte and CD8+
cell to the lung
Contribute to structural lung damage
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Are generated in the thymus and
express the T-cell receptor
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Orchestrate inflammatory process
Effector cells that attract and enhance
inflammatory function, e.g. in
neutrophils and macrophages
Increasing cell numbers correlate with
loss of lung function
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Release
multiple
inflammatory
mediators
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Inflammatory Mediators in COPD
proteases, TNF- , IL-8
Neutrophils
IL-8, IL-6
Macrophages
IFN-, TNF-
CD8+ T-cell
IL-8
Epithelial cell
Small airways
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Small airways are
usually defined as
Noncartilaginous
airways with an
internal diameter
< 2mm
• These airways are
located from
approximately the
eight generation of
airways down to the
alveoli
Emphysema
 Loss Of alveolar
attachments
 Peripheral
airway collapse
Normal
Small Air way
 Reduction in the number of small airways
Mucus Plugging Obstructs Small Airways
in COPD
Normal
COPD
Mucus Plug
  numbers of:
 Goblet cells
 Mucus gland hyperplasia
Reproduced from The Lancet, Vol 364, Hogg JC. "Pathophysiology of airflow limitation in chronic obstructive pulmonary
disease", pp709-721. Copyright © 2004, with permission from Elsevier.
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Lung Parenchyma
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Paraseptal
Emphysema
Distal Acinar
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Paraseptal Emphysema
Paraseptal
Emphysema
Distal Acinar
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alpha-1
antitrypsin
deficiency
Panlobular
Emphysema
Panacinar
emphysema
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Panlobular
Emphysema
Centrilobular emphysema
Proximal ac inar
emphysema
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Emphysema
centrilobular
= upper lobes
= apical region
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Pulmonary
vascular
remodelling
Pulmonary vascular remodelling
Begin early during the course of the
disease
Pulmonary vascular remodelling
1. Thickening of the vessel wall
2. Endothelial dysfunction
3. increased vascular smooth
muscle
4. infiltration of the vessel wall by
inflammatory cells:
o Macrophages
o CD8+
o T lymphocytes
5. There is collagen deposition
6. Emphysematous destruction of
the capillary bed
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Pulmonary vascular Remodeling
Local hypoxia
Pulmonary vasoconstriction
(Chronic Hypoxemia)
Reduction of the pulmonary vascular bed
Blood hyperviscosity
Pulmonary
Hypertension in
COPD
Pulmonary
vascular
resistance
Pulmonary
vascular
Remodelling
Cor Pulmonale
Pulmonary Hypertension
+
Right Ventricular Dysfunction