Disease of lung

: 2013/04/254/30

1.

A.

B.

C.

1.
2.
A.

B.

lingual lobe

3.
A.

Pulmonary arterial system

B.

Bronchial arterial system

Pulmonary arterial system

4. pleural visceral layer

parietal layerpleura cavity

visceral layer
anthracosis

Anatomy of lung

1. airwaybronchusbronchioleterminal bronchiolerespiratory
bronchiole

2. alveolus alveolar ductalveolar sac

alveolar duct alveolar sac

3. acinusrespiratory bronchiole+alveolus
4. lobulecluster of 3-5 terminal bronchioles

Histology of lung

1. bronchus
A.

mucosa goblet cell

lamina propria
B.

smooth muscle

C.

submucosal gland

D.

cartilage C bronchus bronchiole

Lamina propria

Smooth muscle
Submucosal gland

catilage

goblet cell

2. bronchiole
A.

mucosa goblet cell

B.

smooth muscle

C.

Submucosal gland cartilage

bronchiole goblet cell
submucosal glandcartilage

Atelectasis

airspaces

12
1.

obstructive (resorption) atelectasis*

1 asthma 2 chronic bronchitis

3 foreign body aspiration

2.

compression atelectasis*


1 pneumothorax 2
(pleural effusion)
(CHF)

3.

contraction atelectasis

Acute respiratory distress syndrome(ARDS)

1.

ARDS

2.

(clinical and pathologic end result of acutealveolar injury caused by a variety

ofinsults)
(diffuse alveolar capillary damage)

(pulmonary edema)
(rapid

onset of severe respiratoryinsufficiency)

ARDS DAD(diffuse alveolar damage)
3. ARDS
Conditions associated with development of adult respiratory distress syndrome
Infection
Sepsis*

Chemical Injury
Heroin or methadone overdose

Diffuse pulmonary infectious*

Acetylsalicylic acid

(Viral, Mycoplasma, and Pneumocystis

Barbiturate overdose
Paraquat ()

pneumonia; military tuberculosis)

Physical / Injury
Mechanical trauma, including head
injuries*
Pulmonary contusions

Hematologic Conditions
Multiple transfusions
Disseminated intravascular coagulation
(DIC)

Near-drowning

Pancreatitis

Fractures with fat embolism

Burns
Ionizing radiation

Uremia
Cardiopulmonary Bypass

Inhaled Irritants
Oxygen toxicity
Smoke
Irritant gases and chemicals

A. Infection
(1) Sepsis
ARDS
(2) Diffuse pulmonary infectious

B. Physical / Injury (contusions)

C.
D.

4.

Inhaled Irritantssmoke()
Chemical Injury()
(paraquat)

Pathogenesis of ARDS
Alveolar macrophage
IL-8, IL-1, TNF
Neutrophil sequestration, migration to alveolus, activation
leukotrene, protease, PAF
Tissue damage
Intraalveolar edema
Surfactant inactivation
hyaline membrane formation
A.

Early stage
(1) alveolar macrophage
cytokine IL-8IL-1TNF
(2) neutrophil sequestration neutrophil
migrate
(3) neutrophil leukotrieneproteasePAF

a. alveolar tissue damage

b. intraalveolar edema

c. surfactant inactivation

(alveolar collapse)
d.

hyaline membrane formation1 pneumocyte 2

(fibrin)
hyaline membrane

B.

Diffuse alveolar damage(DAD)

(1) exudative stage 1~5
a. acute congestion and edema

b. hyaline membrane formationneutrophil enzyme

pneumocyte pneumocyte(type I or II )
fibrin exudate hyaline
membrane()
(2) organizing stage ()6~7 repair
(organizing fibrosis )
a.
b.

Type II pneumocyte hyperplasiatype I pneumocyte

type II type I cell
fibrosis and thickening of alveolar septum

hyaline memebrane

i.
(fibrin)
ii.

(necrotic debris of
alveolar epithelium)

Type II pneumocyte
hyperplasia(
type II cell )

type II pneumocyte
type I pneumocyte
()

Diffuse pulmonary disease

Diffuse pulmonary disease

1. Obstructive disease(airway)
A.

COPD(Chronic obstructive pulmonary disease)

(1)

Emphysema

(2)

Chronic bronchitis

B.

Asthma

C.

Bronchiectasis

2. Restrictive disease

A.

Idiopathic pulmonary fibersis

B.

Pneumoconiosis

Chronic obstructive pulmonary disease(COPD)

1. (dyspnea)
2. COPD (cigarette smoking)
(enviromental pollution)(noxious exposure)
3.
A.

Emphysema

B.

Chronic bronchitis

Emphysema

1. alveolar space (enlargement of airspace distal to terminal

bronchiole)
2. (destructiont of alveolar septum )alveolar septum

3. (anatomic distribution)
(pathogenesis-related)
A.

Centriacinar emphysema
(1)

95

(2)

(airway obstruction) Respiratory

bronchiole
(3)

Respiratory bronchiole alveolar

duct alveolus ( B)

B.

(4)

(upper lung)

(5)

(Chronic bronchitis)

Panaciar emphysema
(1)

(2)

alveolar duct alveolus ( c)

(3)

(lower lung)

(4)

1-antitrypsin deficiency 1-antitrypsin

1-trypsin(1-trypsin

) 1-antitrypsin
1-trypsin

4. pathogenesis of emphysemaptotease-antiprotease hypothesis

A.

Imbalance between protease(elastase) and antiprotease(1-AT) in lung

(1)

protease(elastase) elastic fiber antiprotease

(1-antitrypsin)
protease = elastase =1-trypsinantiprotease =1-antitrypsin

(2)

(ex:1-antitrypsin deficiency)

B.

inflammationneutrophil()
(1)

neutrophil

neutrophil
a elastase
b free radical antiprotease elastase

 neutrophil
neutrophil elastase free radical elastase

Chronic bronchitis

1. :
A. : productive cough

B.

2. :
A. cor pulmonale():

(1)

preload

(2)
B. right heart failure
3. pathology
A. submucosal gland : a reid index ( 0.4)

reid index
reid index = mucous gland layer /
B. mucus plugging: submucosal gland mucus
( b)
a
submucosal gland layer

()

Bronchial asthma

1.
2. (type I hypersensitivity)
3. : ()wheezing()dyspnea(
)
4. increased responsiveness of tracheobronchial tree to various stimuli(
)


1.
2.
3.
4.

atopic asthma

: dust, pollen(), animal dander(), food

allergic rhinitis(), urticaria(), atopic dermatitis(

)

5. Pathogensis

A. Acute phase: type I hypersensitivity

(1) Mast cell
(2) Subepithelial vagal effect: chemical mediator CN10

(3) bronchoconstriction edema mucus secretion

B. Late phase
(1) 4~8 Mast cell epithelial cell
chemotactic factor /cytokine eosinophils
leukocyte


Pathology of asthma (airway remodeling)
1.

mucus plugging() in bronchus and bronchiole

histamine gland (airway)
lumen
bronchus bronchiole

2.

Curschmann spiral: whorl() of shed epithelium in mucus

3.

Charcot-Leyden crystal: crystalloid() of eosinophil membrane protein

eosinophil

23

4.

edema and inflammatory cell (esp. eosinophil) in bronchial wall

( eosinophil)

5.

submucosal gland hypertrophy

mucus gland

6.

bronchial smooth muscle hypertrophy

()

1 mucus lumen
2
3 smooth m.
4 mucus gland

 lumen
Lumen mucus
mucusplug
(
eosinophil)

1.
2.

Bronchiectasis
obstructive disease

3.

Chronic necrotizing infection of bronchi and bronchioles associated

with abnormal permanent dilation of airway

4.

Airway
A. obstruction of airway (ex. COPDasthma)

B.

infection
obstruction of airway
bronchial wall inflammation and
weakening() dilation ()

Cylindric bronchiectasis

Saccular bronchiectasis

Diffuse interstitial lung disease

(obstructive disease)

Diffuse interstitial lung disease

1.

heterogeneous group
Diffuse interstitial lung disease

2.

chronic diffuse involvement of interstitium

3.

absence of airway obstruction

4.

O2 diffusing capacity
interstitium

5.

secondary pulmonary hypertension right

heart failure

secondary
pulmonary hypertension
right heart failurecorpulmonale
Secondary

6.

end-stage honeycomb lung: cystic spaces with thick

fibrous septa
honeycomb lung

cystic space
thick fibrous septa
interstitium

honeycomb lung

7. Pathogenesis
A.

Activated macrophage neutrophils

ARDS

ARDS

B.

(1)
(2) macrophage neutrophils
(3) Neutrophils oxidants() protease()
type I pneumocyte type II pneumocyte

------------------------------------------------------------------ ARDS
(4) type II pneumocyte fibrogenic&chemotactic cytokines
fibroblast fibroblast
collagen fiber
Macrophage fibrogenic&chemotactic cytokines
ARDS ARDS
honeycomb lung

8.
A.
B.

idiopathic pulmonary fibrosis(IPF)

pneumoconiosis

Idiopathic pulmonary fibrosis(IPF)

1.
982 1/3 2/3
idiopathic pulmonary fibrosis(IPF)

2.
A.

Early stage ARDS Diffuse interstitial

lung disease
(1) Alveolitis ARDS
(2) Edema
(3) Intraalveolar exudate
(4) hyaline membrane
(5) Alveolar septum Septum
(6) Type II pnuemocyte

B.

Advance stageInterstitial fibrous thickening

C.

End stageHoneycomb lung

Honeycomb lung

alveolar space
alveolar septum

lymphocyte

Pneumoconiosis

1. nonspecific lung reaction to inhaled mineraldust in workplace

nonspecific reaction fibrosis

2. 1-5 um particle in terminal airway & alveoli
1-5 um terminal bronchial respiratory bronchial

3. additional effect of tobacco smoking

4. Pneumoconiosis
A. Coal workers pneumoconiosis(CWP)
B. Silicosis
C. Asbestosis

5. Coal workers pneumoconiosis(CWP)

A.

Anthracosis
(1) coal miner urban dweller tobacco
smoker
(2) macrophage

B.

Simple CWP
upper lung

(1) coal macule()carbon-laden macrophage

(2) coal nodule()fibrosis

C.

Complicated CWP
progressive massive fibrosis
multiple black scar
scarring
Coal nodule

fibrosis

multiple black scar

complicated CWP

Black scar

progressive massive fibrosis

honeycomb
lung
6. Silicosis
A. silicon dioxide
B.

most common chronic occupational disease

C.

concentric hyalinized collagen scarsurrounded by eggshell

calcification
fibrosis
hyalinized collagen fiber
eggshell calcification

D.

favor site: upper zone

E.

associated with fibrosis of pleura &hilar node

F.

progressive massive fibrosis honeycomb lung

CWP

Silicosis

fibrosis
scarring

7.

Asbestosis

A.

B.

crystalline hydrated silicateserpentine crystal

amphibole
Tumorigenesissynergy effect withtobacco smoker to develop
bronchogeniccarcinoma

C.

Asbestos-related diseases
(1) Localized pleural fibrous plaque
(2) Pleural effusion
(3) Asbestosis
(4) Bronchogenic carcinoma-5x
50
(5) Mesothelioma-1000X

D.

Pathology of asbestosis
(1) Diffuse interstitial fibrosis from subpleurallower lung

(2) Asbestos body

(fusiform)(beaded rod) asbestos fiber

(iron-containing proteinaceous material)
(golden brown)
H&E stain

Pulmonary vascular disorder

Pulmonary embolism and infraction

1.
A.

B.(deep vein of leg)(95)

thrombin
C.

D.

embolism

bronchial artery system

E. 10
pulmonary embolism
2. Pathology of pulmonary embolism
embolism

A.

Large embolism
(1)

Saddle embolus

(pulmonary trunk)

(2)

Acute cor pulmonale(

B.

Small embolism

(1)

Subpleural wedge-shaped hemorrhagic infraction with apex toward

hilum

(wedge-shaped) hemorrhagic
necrosis
hemorrhagic necrosis base
pleural
(hilum)

(2)

(lower lung) 75

(3)

embolism

embolism embolism

Septic infract

(4)

a (ex )
b
Septic infract
lung abscess

Pulmonary hypertemsion

1/6 90-100 mmHg

15 mmHg

1. Primary pulmonary hypertemsion

2. Secondary pulmonary hypertemsion
A.

Chronic obstructive or interstitial lung disease

airway interstitial
COPDinterstitial lung disease

Congenital or acquired heart disease left to right shunt

B.

( VSDventricular septum
defect)
3. Pathology of pulmonary hypertemsion
A.

(atherisclerosis)

B. small artery ateriole

(1)

medial smooth muscle layer

(2)

intimal fibrosis() lumen

Pulmonary infection
Community-acquired acute pneumonia
Community-acquired atypical pneumonia Lung abscess
Tuberculosis

Community-acquired acute pneumonia

1.
Community-acquired
2. (consolidation)

3.
A.

(etologic agent)

pneumococcal pneumonia
B. (nature of host reaction)
(suppurative pneumonia)
C.

(gross anatomic distribution)

(lobar pneumonia)( bronchopneumonia)

4. (lobar pneumonia)
A.

(lobar pneumonia)
B.(acute suppurative pneumonia)
C.

95 pneumococci

D.

lobar pneumonia
(1)

congestion (36 hrs):


aveolar sapce

(2)

red hepatization(36~48 hrs)

(hepatization)
aveolar sapce
fibrin
(3)

gray hepatization (2-3 days)

neutrophilfibrin
fibrinosuppurative exudate
(4)

resolution (1-2 wks)

neutrophilfibrin

congestion

red hepatization

(PMN)

gray hepatization

5. ( bronchopneumonia)
A.

(lobar pneumonia)

( bronchopneumonia)(patchy
consolidation)

B.(patchy consolidation)

C.

bronchitis bronchiolitis

D.

pneumococci streptococci

staphylococci
E.
F. (aspiration pneumonia)

bronchitis
bronchiolitis
(aspiration pneumonia)( aspiration pneumonia
bronchopneumonia )

bronchopneumonia
lobar pneumonia

Community-acquired atypical pneumonia

1.
2. (pulmonary interstitium)
interstitial pneumonitis( pneumonia
pneumonitis pneumonia)(
..)

3. viral(mycoplasmal) SARS
H7N9
4.
fibrosis

lymphocytealverlar
septum

Lung abscess

1. pneumonia

2.

3. Lung abscess
A.

oropharyngeal surgery

B.Sinobronchial infection

C.

Dental sepsis

Bronchiectasis

D.

Lung abscess
space

cavitation

Tuberculosis TB

1. TB
A. Mycobacterium tuberculosis air-borne
Mycobacterium tuberculosis lung apex

B.

C. Mycobacterium tuberculosis nonspore-forming

nonmotile
D. acid-fast TB
E.

Pulmonary tuberculosis

(1)

Primary TB TB

(2)

Sencondaryreactivation TB TB

(3)

Progressive pulmonary TB

TB
2. Primary TB

A.
Ghon complexsubpleural lesion & hilar
LN enlargement
subpleural
macrophage

granulomatous
inflammation caseous
necrosis
caseous necrosis

Langhans giant cell

Epitheloid cell macrophage

 HE TB
AIDS acid-fast
TB
macrophage TB

3. Secondary reactivation pulmonary TB

A. TB
B. Primary TBsubclinical infection
Ghon complex
reactivationTB
C. lung apex
D. small consolidation
E.Caseating granulomatous infalmmation
(1)

Fibrocalcific scar

(2)

Progressive pulmonary TB
caseous necrosis

4. Progressive pulmonary TB
A. Cavitary fibrocaseous TB
(1)

TB granulomatous inflammation airway

bronchiole caseous necrosis airway

lumen
(2)

lung apex

(3)

Endobronchial spreadingcaseous necrosis

airway lumen GI tract

(4)

Lymphatic spreadingcaseous necrosis

TB lymphadenitis
Hematogenous spreadingcaseous necrosis

(5)

miliary TB

consolidation
TB

B.Miliary TB
(1)

caseous necrosis

1-3mm

1-3mm

Bronchogenic carcinoma

1. Bronchogenic carcinoma
primary
2.
secondarymetastatic

3.

4. squamous cell carcinomasmall cell

carcinoma

Etiology and pathogenesis of bronchogenic carcinoma

1.

A.

Tabacco smoking

B.

Industrial hazardasbestos

C.

D.

Molecular genetics
(1)

Oncogene
a.small cell carcinoma c-myc
b. adenocarcinoma K-ras
EGFR
30% EGFR mutation

(2)

tumor suppressor genep53

p53

Pathology of bronchogenic carcinoma

1.
A.

central-located 75%

B.

peripherally-located adenocarcinoma

25% peripherally-located

2. desmoplasiafibrosis

3. local invasion pleural

pericardial

4. nodal involvement hilar

tracheal
mediastinal
5. distant metastasis

A.

B.

peripherally-located

centrally-located
necrosis

Histologic classification of bronchogenic carcinoma

1. Non-small cell carcinoma70-75%

A.

Adenocarcinoma30-35%
(1)

Bronchioloalveolar carcinoma

B.

Squamous cell carcinoma25-30%

C.

Large cell carcinoma10-15%

2. Small cell carcinoma20-25%

98

Squamous cell carcinoma

1.
2. Microscopic finding
A.

Keratinization

B.

Intercellular bridging

3. centrally-located bronchus
squamous
metaplasia SCC

4. necrosis
cavitation
5. local spreadinglate metastasis

Adenocarcinoma of lung
1.
2. Tumor cells
3. (SCC )
4. Tumor cells (BAC )
5. Bronchioloalveolar carcinoma (BAC)
A. adenocarcinoma of lung
B. terminal bronchiole alveolar epithelial
cell
C. solitary, multiple diffuse
D. Tumor cells tall, columnar to cuboid epithelial cells alveolar septum
invase alveolar cells()()

E.

Small cell carcinoma

1.
2. Centrally-located
3.

4. Oat cell type: Tumor cells (

lymphocyte)

5. Derived from neuroendocrine cell (

neuropeptide)
6. chemotherapy/radiotherapy
7. paraneoplastic syndrome : tumor cell
hormone
ADH
ACTH

Parathyroid
hormone-related
peptide
calcutonin

Glucocorticoid cushing
syndrome

small cell
carcinoma
small cell
carcinoma
squamous cell
carcinoma

c cell lung

carcinoma

8.

recurrent laryngeal n.

dysphagia :

Pancoast tumor-lung apex()

1.

Pancoast syndrome
A. nerve lung apex
()
B. Sympathetic plexus-severe pain along ulnar nerve

2.

Horner syndrome
A.
B. : ()ptosis miosis
anhidrosis

Superior vena cava syndrome-helium()

A. Small cell carcinoma squamous cell carcinoma
B. Tumor

Management of bronchogenic carcinoma

A. Nonsmall cell carcinoma(SCCAdenocarcinomalarge cell carcinoma
):
(1)
(2) Adenocarcinoma: DNA EGFR mutation

B. Small cell carcinoma: chemotherapy/radiotherapy

 Pleural effusion
A. :

B.
(1) Inflammatory pleuritis
a. Serous/fibrinous:
b. Empyema ex:
c. Hemorrhagic pleuritis RBC
()
(2) Noninflammatory
a. Hydrothorax :
b. Hemothorax : trauma