경희대학교 의과대학·의학전문대학원

(1)

Pathology of the Lung

2009. 11. 23 2009. 11. 23

병 리 과 김 교 영

(2)

Respiratory system

N

l

• Normal

• Congenital anomaly (선천기형)

Obstructive pulmonary disease (폐쇄폐질환)

• Obstructive pulmonary disease (폐쇄폐질환)

• Restrictive pulmonary disease (제한폐질환)

• Acute lung injury

Acute lung injury

• Vascular origin

• Infections

• Tumors

(3)

• Normal

• Congenital Anomaly (선천기형)

• 폐확장이상

– Atelectasis (무기폐, collapse)

• Chronic Obstructive Pulmonary Disease

(COPD) 만성폐쇄성폐질환

(COPD), 만성폐쇄성폐질환

– Emphysema (폐기종)

– Chronic bronchitis (만성기관기염)

Chronic bronchitis (만성기관기염)

– Bronchiectasis (기관지확장증)

(4)

Normal Lung

• Cardinal function:

E h f b i i d i d h bl d

Normal Lung

– Exchange of gases between inspired air and the blood

• Developmentally, outgrowth from ventral wall of foregut.p y, g g • Weight:

350∼425 gm (normal adult lung) – 350∼425 gm (normal adult lung)

• 좌우 주 기관지는 제 4-5 흉추 수준에서 나뉜다. • Lobes: 3 (right), 2 (left)

• Branching airway는 dual arterial supply를 받는다.

– Pulmonary artery ← Right ventricle

B hi l t A t

(5)

(6)

Normal Lung

• Bronchus (기관지) :

– Right side:

ti l d di tl i li ith t h • more vertical and directly in line with trachea • vomitus, blood, foreign body 등이 잘 들어감

B h 에는 C 모양의 연골이 있고 뒤쪽은 – Bronchus에는 C 모양의 연골이 있고, 뒤쪽은 평활근으로 구성된 막으로 연골이 없다. – 폐 내에서는 기관지벽 전체를 평활근이 둘러 싸서 수축 시 기도폐쇄가 올 수 있다 싸서 수축 시 기도폐쇄가 올 수 있다.

– Submucosal glands(+), smooth muscle(+), cartilage (+)

(7)

Bronchiole (

세기관지)

Bronchiole (

세기관지)

• Cartilage (-), submucosal gland (-)

• Smooth muscles (+)

• ≤ 2mm in diameter (terminal bronchiole,

(8)

R

i t

Respiratory

epithelium

(9)

Neuroendocrine cell (Kulchitsky cell)

• Bronchial mucosa에는 neuroendocrine cell (Kulchitsky cell)이 있Bronchial mucosa에는 neuroendocrine cell (Kulchitsky cell)이 있 으며 serotonin, calcitonin, gastrin-releasing peptide (bombesin) 등의 신경분비과립을 가진다.

(10)

"Clara cells" :

– Columnar, nonciliated cells

– Terminal bronchiole level에서 도달하면서 나타남 (goblet cell은 사라짐)

– 80% of epithelium of terminal bronchiole80% of epithelium of terminal bronchiole – Secretory function (apical dome-shaped)

f l i EM (전자현미경)

• presence of secretory granules in EM (전자현미경) (nonciliated granulated cells with surfactant)

– Main progenitor cells after bronchial injury

– 세기관지에 염증병변이 있을 때는 Clara cell의 수가 감소하면서 술 잔세포 화생 (goblet cell metaplasia)이 일어나 점액생성이 증가 하게 된다.

(11)

(12)

(13)

Lobule (폐소엽): 3∼5개의 terminal

b

hi l 의 l t

bronchioles의 clusters

Acinus (세엽,= terminal respiratory unit):7mm

– Lung distal to a terminal bronchiole

– Spherical in shape, site of gas exchange

A i

구성

Acinus 구성

1. Respiratory bronchioles

Terminal Bronchiole

y

2. Alveolar ducts

3 Alveolar sacs

3. Alveolar sacs

4. Alveoli

(14)

Micro :

Alveolar wall

:

(1) Capillary endothelium

(2) Basement membrane

& interstitial tissue

(3) Alveolar epithelium

전자현미경

- type I & II pneumocytes

(4) Alveolar macrophage

전자현미경

(4) Alveolar macrophage

• loosely attached to the epithelial cells or lying free within the alveolar space

• derived from blood monocyte and belonging y g g to the mononuclear phagocytic system

(15)

Pores of Kohn

: passage of bacteria and exudate

between adjacent alveoli

Pore of Kohn

Legionnaire’s pneumonia

(16)

(17)

Alveolar Epithelium

1) T

I

(

b

1) Type I pneumocyte (membranous

pneumocyte)

Fl tt

d

l t

lik

t

– Flattened, plate-like pavement

– Covering 95% of alveolar surface

2) Type II pneumocyte

d d

– Rounded

– Source of pulmonary surfactant, contained in

osmophilic lamellar bodies

– Main cell type involved in the repair of alveolar

epithelium after destruction of type I cell

p

yp

(18)

Interstitium (사이질)

• Elastic fiber (탄력섬유) • Collagen fiber

• FibroblastFibroblast

• Smooth muscle

• Mast cell, lymphocyte, monocyte

monocyte

microvilli

Microscopic structure of the alveolar wall Microscopic structure of the alveolar wall. - Note that the basement membrane

(yellow) is thin on one side and widened where it is continuous with the interstitial space. Portions of interstitial cells are shown.

(19)

전자현미경

Type I Alveolar space Type II Type I Capillary lumen RBC RBC Endothelium Type I Alveolar space

(20)

Pulmonary surfactant:

y

• Thin film of phospholipid, mostly phosphatid lcholine (lecithin) phosphatidylcholine (lecithin) • Type II epithelial cells에서 합성

– osmiophilic lamellated bodies (LB)에 저장됨

(21)

Pulmonary defense mechanisms

y

• Daily, exposed to > 10,000 liters of air dusts,

chemicals, & microorganisms

• Filtering and clearing mechanisms

1. Nasal clearance :

– Sneezing & blowing, swallowing

2. Tracheobronchial clearance :

M ili ti ll i / t t – Mucociliary action, swallowing/expectorate

3. Alveolar clearance :

– Alveolar macrophagesp g

Particles (dusts) deposited

> 10 m in nose & pper air a s > 10 μm : in nose & upper airways 3∼10 μm : in trachea & bronchi

(22)

Impairment of normal defense mechanisms

I

i

t d

t

i

f

h

fl

• Impairment due to suppression of cough reflex

(drugs, virus)

• Injury to mucociliary apparatus (smoking virus

Injury to mucociliary apparatus (smoking, virus,

Kartageners syndrome)

• Injury to macrophages (tabacco, alcohol, anoxia)

• Pulmonary congestion/edema, accumulation of

ti

(

ti fib

i )

secretions (cystic fibrosis)

• Pneumonia (폐렴)

– Impairment of normal defense mechanisms – Lowered host resistance

(23)

Congenital Anomalies (선천기형)

• Developmental defects of the lung

1. Agenesis (무형성) or hypoplasia (발육기능상실) of both lung, one lung or single lobe g g

2. Tracheal and bronchial anomalies (atresia, stenosis, tracheoesophageal fistula)p g )

3. Vascular anomalies

4. Congenital lobar overinflation (emphysema, 폐기종) 5 Congenital cysts (선천성 낭)

5. Congenital cysts (선천성 낭)

6. Congenital pulmonary airway malformation (CPAM, CCAM) 7. Intralobal and extrapulmonary lobar sequestration (폐격리증)

(24)

(25)

(26)

(27)

Congenital cyst (선천성 낭)

• 원시 foregut의 조각이 비정상적으로 떨어져 나온 상태로 흔히 hilum or middle

mediastinum에 위치한다.

벽구조물에 따라 bronchogenic cyst (most common) esophageal or enteric

• 벽구조물에 따라 bronchogenic cyst (most common), esophageal or enteric

cyst

• Bronchogenic cyst

– 폐의 아무 곳에나 주로 single, 드물게 multiple cystic space로 생길 수 있다. – 크기: 수 mm부터 5cm 이상이 되기도 함 – 보통 bronchi나 bronchiole에 인접해 있으며 기관지 상피로 덮여 있다. – 기관지와의 연결은 보통 없지만 드물게 있을 수도 있다. – mucous secretion 또는 공기로 차있다. – 낭종벽에는 점액샘 혹은 연골, smooth muscle등이 관찰됨 – complications :

• 감염, 화농, 폐농양, rupture into the bronchi

→ hemorrhage, hemoptysis, rupture into the pleura

(28)

Bronchopulmonary sequestration

(폐격리)

폐의 lobe이나 segment가 기도와 정상적인 연결을 • 폐의 lobe이나 segment가 기도와 정상적인 연결을 갖지 않는 것. • 혈류공급은 대동맥에서 받는다. (1) intralobar (폐내형) 1) 폐실질에서 관찰되고,

2) 호발 부위는 좌하엽의 posterior basal segment 2) 호발 부위는 좌하엽의 posterior basal segment 3) 반복감염, 기관지확장증과 흔히 관련된다. (2) extralobar (폐외형) 1) lung 바깥쪽 (visceral 흉막 외부) 2) 흉곽, 종격동 어디에서나 출현할 수 있다 (주로 left 90 %) 3) 주로 유아에서 흔하다. 4) 다른 선천성 기형과 흔히 동반 (50-70%) 4) 다른 선천성 기형과 흔히 동반 (50 70%) – 가로막 탈출 (diaphragmatic hernia); 20%에서 동반

(29)

(30)

(31)

(32)

Congenital Cystic Adenomatoid Malformation (CCAM)

(선천성 낭종성 샘종양 기형)

Congenital Pulmonary Airway Malformation (CPAM)

1)

A hamartomatous lesion of the lung, 1/5000 live

births

2)

Variously sized intercommunicating cysts lined by

2)

Variously sized intercommunicating cysts lined by

"adenomatoid" cuboidal to ciliated pseudostratified

columnar epithelium

3)

Associated with bronchial atresia

4)

Usually present with respiratory distress (호흡곤란)

4)

Usually, present with respiratory distress (호흡곤란)

in neonates

5)

Fi

h l

i

i ti

분류기준

5)

Five morphologic varieties 분류기준

– Size and number of the cysts

(33)

CCAM (CPAM)

(

)

• Type 0 : tracheal / bronchialType 0 : tracheal / bronchial • Type 1 : bronchial / bronchiolar • Type 2 : bronchiolar

• Type 3 : bronchiolar / alveolar duct • Type 3 : bronchiolar / alveolar duct • Type 4 : peripheral

(34)

CCAM (CPAM)

(

)

Type Incidence Gross Microscopy Other features

0 1-3% Solid Pseudostratified Neonates

0 1-3% Solid Pseudostratified ciliated cells Mucous cells Cartilage glands Neonates Other malformations Poor prognosis

(incompatible with life)

Cartilage, glands (incompatible with life)

1 60-70% Large cysts,

3-10 cm

Pseudostratifined

ciliated cells, often with rows of mucous cells

Presentation may be late

Good prognosis

rows of mucous cells _{Good prognosis}

(resectable)

2 10-15% Small uniform

cysts < 2 cm

Simple columnar ep. Striated muscle in 5%

Neonates

Other malformations

cysts, < 2 cm _{Striated muscle in 5%.} _{Other malformations}

Poor prognosis

3 5% Solid, bulky

lesion cysts

Simple cuboidal ep. Male neonates, a/w

maternal lesion, cysts <0.2 cm maternal polyhydramnios Poor prognosis

4 15% Large cysts Flattened ep (type 1 Neonates infants

4 15% Large cysts (<7 cm), in the peripheral lung Flattened ep.(type 1 pneumoncytes) Neonates, infants Good prognosis

(35)

(36)

Hypoplasia

(37)

CCAM Type 0

(38)

(39)

(40)

(41)

(42)

(43)

폐확장 이상

• ATELECTASIS (무기폐, Collapse)

– 폐의 불완전한 팽창 (neonatal atelectasis) 또는 이미

팽창된 폐조직의 허탈 (collapse)로 인하여 공기가 별

로 없는 폐실질을 형성하는 것.

– 심하면 산소결핍에 이어 감염을 초래함.

– 출생 시, 생후 수일 내 관찰되기도 하며 (neonatal

atelectasis), 생후 어느 때나 발생할 수 있다.

(44)

Atelectasis (무기폐)

• 종류

1 Obstruction or Resorption (폐쇄성 또는

1. Obstruction or Resorption (폐쇄성 또는

흡수성) Atelectasis

2. Compression (압박성) Atelectasis

3. Patchy (반상) Atelectasis

4. Contraction (수축성) Atelectasis

(

)

(45)

1. Obstruction or Resorption Atelectasis

(폐쇄성 또는 흡수성 무기폐)

기도의 완전폐쇄로 폐포 내에 갇힌 공기는 흡 • 기도의 완전폐쇄로 폐포 내에 갇힌 공기는 흡 수되나 혈류는 유지된다. 폐용적 감소로 종격동 (mediastinum)이 병변 • 폐용적 감소로 종격동 (mediastinum)이 병변 쪽으로 밀릴 수 있다 원인: • 원인: – 지나친 분비물 (즉, mucous plug) 혹은 세기관 지 내의 삼출물 • 원인질환:

– asthma, chronic bronchitis, bronchiectasis, postoperative state, 이물흡입 등 p p , • 기관지종물도 무기폐를 유발할 수 있지만, 기 도를 불완전 폐쇄하기 때문에 대부분 국소성 폐기종을 유발한다 폐기종을 유발한다.

(46)

2. Compression atelectasis

(압박성 무기폐)

• 흉강이 exudate tumor blood

• 흉강이 exudate, tumor, blood,

air 등으로 찰 경우

• peritonitis, subdiaphragmatic

abscess 등으로 또는 seriously

ill 환자에서 수술 후

_{Æ 횡경막이}

ill 환자에서 수술 후

_{Æ 횡경막이}

많이 올라가서 (basal

atelectasis 생김)

• 종격동 (mediastinum)이 병변으

종격동 (mediastinum)이 병변으

로 부터 멀어진다.

(47)

3 C

t

ti

t l

t

i (수축성 무기폐)

3. Contraction atelectasis (수축성 무기폐)

– 폐나 흉막의 섬유화로 인해 폐의 팽창을 방해폐나 흉막의 섬유화로 인해 폐의 팽창을 방해 하여 발생

Significant atelectasis reduces oxygenation • Significant atelectasis reduces oxygenation

and predisposes to infection.

Because the collapsed lung parenchyme can • Because the collapsed lung parenchyme can

be re-expanded, atelectasis is

a reversible

disorder

(except that caused by contraction)

(48)

Obstructive Vs. Restrictive Pulmonary Disease

; Based on pulmonary lung function test

1. Obstructive (폐쇄성) disease: 기도폐쇄로 인

1. Obstructive (폐쇄성) disease 기도폐쇄로 인

한 air flow저항의 증가 (airway disease)

(1) FEV1감소 (Forced expiratory volume at 1 second,

노력성 1초간 호기량)

(2) Expiratory airflow obstruction due to

1) Anatomic airway narrowing: eg) asthma

2) Loss of elastic recoil of the lung: eg) emphysema – Emphysema (폐기종)

– Chronic bronchitis (만성기관지염)Chronic bronchitis (만성기관지염) – Bronchiectasis (기관지확장증) – Asthma (기관지 천식)

(49)

Obstructive Vs. Restrictive Pulmonary Disease

2. Restrictive (제한성) disease

– Reduced expansion of lung parenchyme

T

l l

i 의 감소

– Total lung capacity의 감소

– Normal or proportionately reduced expiratory flow

rate

– 원인

)

1) Chest wall disorder with normal lung:

• Neuromuscular disease (eg. poliomyelitis), severe obesity, pleural disorder, kyphoscoliosis

2) Acute and chronic interstitial and infiltrative disease:

• Acute – ARDS (acute respiratory distress syndrome)

Ch i d t di ( i i ) t f th

• Chronic - dust disease (pneumoconiosis), most of the infiltrative conditions

(50)

Chronic Obstructive Pulmonary Disease

(

만성 폐쇄폐질환)

(COPD, 만성 폐쇄폐질환)

• 호흡곤란을 주 증상으로 하는 일단의 상태로서

• 폐 내부 공기흐름의 만성적 또는 반복적인 폐쇄를 동반

한다

한다.

– Emphysema (폐기종)p y (폐기종) – Chronic bronchitis (만성기관지염) – Asthma (천식) – Bronchiectasis (기관지확장증)Bronchiectasis (기관지확장증)

– Small airway disease (SAD), Bronchiolitis (세기관지염)

• 환경공해, 흡연, 다른 해로운 인자에 노출되는 기회가 증

가함에 따라 최근 수십 년간 COPD의 발병이 급속도로

증가했다

(51)

Table 15-3. Disorders Associated with Airflow Obstruction: The Spectrum of Chronic Obstructive Pulmonary Disease The Spectrum of Chronic Obstructive Pulmonary Disease

Clinical Term Anatomic Site Major Pathologic Changes Etiology Signs/Symptoms Clinical Term Anatomic Site Major Pathologic Changes Etiology Signs/Symptoms Chronic bronchitis Bronchus Mucous gland hyperplasia,

hypersecretion

Tobacco smoke, air pollutants

Cough, sputum production

Bronchiectasis Bronchus Airway dilation and scarring

Persistent or severe infections

Cough, purulent sputum, fever Asthma Bronchus Smooth muscle

hyperplasia, excess mucus, inflammation Immunologic or undefined causes Episodic wheezing, cough, dyspnea

Emphysema Acinus Airspace enlargement; wall destruction

Tobacco smoke Dyspnea

Small airway disease, bronchiolitis

Bronchiole Inflammatory

scarring/obliteration

Tobacco smoke, air pollutants,

miscellaneous

(52)

Schematic representation of overlap between

chronic obstructive lung diseases

(53)

Emphysema (폐기종)

Definition

:

• Definition

:

– Terminal bronchiole 이하 부분 (Acinus)의 airspace가 비정상 적으로 영구히(irreversible) 늘어난 상태로서 폐포벽의 파괴가 동반되며 뚜렷한 섬유화는 동반하지 않는다

동반되며, 뚜렷한 섬유화는 동반하지 않는다. – overinflation인 경우는 조직 파괴가 없다.

1. 분류와 특징: lobule내의 anatomic distribution에 따라

Centriacinar (Centrilobular) Emphysema (중심세엽 중심소엽) – Centriacinar (Centrilobular) Emphysema (중심세엽, 중심소엽) – Panacinar (Panlobular) Emphysema (범세엽, 범소엽)

– Paraseptal (Distal Acinar) Emphysema (말단세엽, 부격막) – Irregular Emphysema (불규칙)

(54)

• Centriacinar (Centrilobular) Emphysema

1) 가장 흔하다(95%이상)

2) 주로 폐상엽 (특히 apical segment)에서 흔하고, 더 심함 3) Respiratory bronchiole의 중심 또는 proximal부를 침범하며 3) Respiratory bronchiole의 중심 또는 proximal부를 침범하며

distal alveoli는 유지됨, 심해지면 distal도 involve

4) Bronchi bronchiole septa에 흔히 염증 동반 septal wall에 많 4) Bronchi, bronchiole, septa에 흔히 염증 동반, septal wall에 많

은 양의 black pigment

5) Heavy smoker에서 종종 만성기관지염과 동반하여 잘 생김 5) Heavy smoker에서 종종 만성기관지염과 동반하여 잘 생김 6) Coal worker's pneumoconiosis도 매우 유사한 병변을 보이는

데 발생기전상 담배와 coal dust가 이 두 가지 질병에서 중요한 데 발생기전상 담배와 coal dust가 이 두 가지 질병에서 중요한 역할을 한다는 것을 의미함.

(55)

• Panacinar (Panlobular)

h

Emphysema

1) Respiratory bronchiole부터 폐포 끝까지

균일하게 acinus전체가 확장됨

2) 폐의 lower zone과 anterior margin에 흔

하고 base에서 더욱 심함

3) alpha-1-antitrypsin (antiprotease) 결핍

3) alpha 1 antitrypsin (antiprotease) 결핍

(56)

• Paraseptal (Distal Acinar) Emphysema

1) Acinus의 distal부가 침범되고 근위부는 정상이다

1) Acinus의 distal부가 침범되고 근위부는 정상이다.

2) Pleura에 인접하여 lobule connective tissue septa을

p

따라서, 그리고 lobule margin에서 흔함.

3) Upper half 에서 심함 fibrosis scarring 또는

3) Upper half 에서 심함, fibrosis, scarring, 또는

atelectasis 부위에 인접

4) 흔히 젊은 층에서 spontaneous pneumothorax (자연

기흉)를 유발한다.

5) 0.5㎜이하～2.0㎝이상 직경의 multiple, continuous,

enlarged airspaces → 때로는 cyst-like structure가

됨

(57)

• Irregular Emphysema

1) Acinus가 불규칙하게 침범되고, 거의 대부분 scarring과 연관 됨

2) 부검을 해보면 대부분의 폐에서 한 두개의 scar는 찾을 수 있으 므로, 이 type이 가장 흔한 type일지도 모른다.

• Centriacinar와 panacinar emphysema만이 임상적으

로 심한 airflow obstruction을 유발.

(58)

Emphysema

Lung tissue destruction

“Imbalance

protease-antiprotease

”

+

(59)

4. 흡연에 의한 emphysema 발생기전

(1) 흡연가의 alveolus내에는 neutrophil과 macrophage가 더 많다.

– Direct chemoattractant effect of nicotine and effect of reactiveDirect chemoattractant effect of nicotine and effect of reactive oxygen species Æ activate transcription factor NF-kB Æ

encode TNF and IL8 (neutrophil chemotactic factor) Æ neutrophil를 끌어 들이고 활성화시킨다.

(2) 흡연은 neutrophil에서 protease (neutrophil elastase, proteinase3, cathepsin G) 유리를 촉진한다.

(3) 흡연은 macrophage의 elastolytic protease activity를 증가시 킨다. (macrophage의 elastase는 α1-AT에 의하여 억제되지 않고 α1-AT을 분해한다 )

않고, α1 AT을 분해한다.)

(4) 담배연기의 reactive oxygen species (free radical)은

antioxidant(superoxide dismutase glutathione) 를 감소시키 antioxidant(superoxide dismutase, glutathione) 를 감소시키 고 α1-AT을 억제한다 (“functional” α1-AT deficiency).

(5) 흡연가에서는 전체적으로 antielastase activity가 떨어짐으로써 (5) 흡연가에서는 전체적으로 antielastase activity가 떨어짐으로써

(60)

Pathogenesis of Emphysema

(61)

Other types of Emphysema

Compensatory Emphysema (Compensatory

H

i fl ti

) 대상 폐기종

Hyperinflation) , 대상 폐기종

– 폐엽절제후 residual lung parenchyme의 hyperexpansion – Dilatation of alveoli

– No destruction of septal wall

Senile Emphysema (노인 폐기종)

– Age related, larger alveolar duct & smaller alveoli, without loss of elastic tissue or destruction of lung substance

Obstructive Overinflation (폐쇄과팽창)

1) 종양 또는 이물이 기도를 막아서 공기가 갇혀 폐가 팽창함 2) 이들이 b ll l 처럼 작용하여 i i ti 은 가능 i ti 2) 이들이 ball valve처럼 작용하여 inspiration은 가능, expiration

은 잘 안됨.

3) 또는 기관지가 완전 폐쇄되어 과팽창됨 - 막힌 부위 이하에서 pore of Kohn 또는 bronchioloalveolar connection (=canal of pore of Kohn, 또는 bronchioloalveolar connection (=canal of Lambert)로 측부환기가 일어남

(62)

Other types of Emphysema

Bullous Emphysema (기포 폐기종)

Other types of Emphysema

– 어떤 형태의 emphysema든 1 cm 이상의 subpleural

bullae 혹은 bleb형성하는 경우를 말함

때

과 관련

– 때로 old tuberculosis scarring과 관련

– most subpleural, near the apex

Rupture of bullae

_{Æ pneumothorax (기흉)}

– Rupture of bullae

_{Æ pneumothorax (기흉)}

Interstitial Emphysema (사이질 폐기종)

1) lung, mediastinum, subcutaneous tissue의

connective tissue stroma 내로 air가 들어 간 상태

connective tissue stroma 내로 air가 들어 간 상태.

2) coughing + bronchiolar obstruction → ↑pressure

→ alveolus의 파열

(63)

Morphology

p

gy

Emphysema

Gross examination of lungs fixed in a state of

inflation

Micro:

Abnormal fenestrations in wall of alveoli

– Abnormal fenestrations in wall of alveoli

– Complete destruction of alveolar septal walls

Blebs or bullae

(64)

Centrilobular

A, Centriacinar emphysema. Central areas show marked emphysematous damage (E), surrounded by relatively spared alveolar spaces.

B, Panacinar emphysema involving the entire

pulmonary architecture.

(65)

Bullous emphysema with large subpleural bullae

(66)

Clinical Course of Emphysema (폐기종)

1. 폐실질의 기능이 1/3이상 저하되어야 증상이 나타나고 panacinar의 경우가 심하다.

2 dyspnea : 첫 증상으로서 서서히 지속적으로 진행한다

2. dyspnea : 첫 증상으로서 서서히 지속적으로 진행한다.

3. cough, wheezing : 주된 증상으로 나타나기도 하며 asthma로 혼동되기 쉽다. 4. 기침 및 가래 : 다양하게 나타나고, 흔히 bronchitis의 정도와 연관.

5. 체중감소

6. 술통형 가슴 (barrel chest), pinched face, breath through pursed lips

7. 숨 내쉬는 시간이 길어진다 (slowing of forced expiration), sit forward in a

h h d iti

hunched-over position

8. overventilation으로 oxygenation은 유지됨 : pink puffer (복어)

(cf. chronic bronchitis : recurrent infection, abundant purulent sputum,

h i h i bl bl t 청어)

hypercapnia, severe hypoxemia - blue bloater, 청어) 9. COPD의 사망원인:

– Respiratory acidosis and coma

– RHF (right heart failure)

(67)

Chronic Bronchitis (만성기관지염)

• 진단기준: clinically

Chronic Bronchitis (만성기관지염)

진단기준: clinically

– 가래를 동반한 기침을 1년에 최소 3개월 이상, 연속으로 2년 이 상 지속되는 경우

• Habitual smoker(4～10배), smog 많은 도시인에 많음

• 수년간 지속되면

– Progress to COPDProgress to COPD

– cor pulmonale (폐성심), heart failure

– atypical metaplasia and dysplasia (cancerous transformation) 를 유발한다

를 유발한다.

(68)

Pathogenesis of

Chronic Bronchitis

• Two sets of factors

1 Primary or initiating factor 1. Primary or initiating factor

• Chronic irritation by inhaled substances (smokes (90%), pollutants)

2. Secondary factor

• Microbiologic infections

• Airway obstruction

– Earliest:

• Hypersecretion of mucus in the large airways

– Persistent:

M k d i i G bl t ll f ll i

(69)

Chronic Bronchitis

Morphology

• Increase the size of mucus glands

of trachea and bronchi –

↑Reid index

(b c / a d)

↑Reid index

(b-c / a-d)

(정상 : < 0.4, Chronic bronchitis : > 0.5)

• Severe cases

Æ

L

i l b t

ti

Æ

Luminal obstruction

(70)

Chronic bronchitis

Normal

(71)

Chronic bronchitis vs Emphysema

Chronic bronchitis vs. Emphysema

(Hypoxemia) (Over-ventilate and

(72)

Schematic representation of

evolution of chronic bronchitis (left) and emphysema (right)

and emphysema (right).

• Although both can culminate in chronic bronchitis and emphysema the

bronchitis and emphysema, the

pathways are different, and either one may predominate.

• The dashed arrows on the left indicate that in the natural history of chronic bronchitis,

• It is not known whether there is a

predictable progression from obstruction in small airways to chronic (obstructive) bronchitis.

(73)

Bronchial Asthma (기관지 천식)

Definition

• A chronic inflammatory disorder of the airway

tnat causes recurrent episodes of wheezing,

p

g

breathlessness, chest tightness, and cough,

particularly at night and/or in the early morning.

p

y

g

y

g

• Increased airway responsiveness (과민반응) to

a variety of stimuli, resulting in

Episodic bronchoconstriction

– Episodic bronchoconstriction

– Inflammation of the bronchial walls

Increased mucus secretion

(74)

Bronchial Asthma

1) A

i

ll

i

h

1) Atopic or allergic asthma

– Most common type

Type I IgE mediated hypersensitivity reaction – Type I IgE-mediated hypersensitivity reaction

• Serum IgE ↑

– Begins in childhood, Familial history (+), Skin test (+) T i d b d t ll i l d d f d t – Triggered by dusts, pollens, animal dander, foods etc.

2) Non-atopic asthma

)

p

– Triggered by respiratory tract infection

• rhinovirus, parainfluenza virus

F ili l H ( ) – Familial Hx (-)

– Serum Ig E: normal, skin test (-)

(75)

Bronchial Asthma

3) Drug-induced asthma

Aspirin sensitive asthma (small dose) – Aspirin-sensitive asthma (small dose)

– Inhibiting the cyclooxygenase pathway of archidonic acid metabolism without affecting the lipoxygenase route thus tipping the balance toward elaboration of affecting the lipoxygenase route, thus tipping the balance toward elaboration of the bronchoconstrictor leukotrienes.

4) Occupational asthma) p

– Gas (toluene)

– Fumes (epoxy resins, plastics)

– Organic and chemical dusts (wood, cotton, platinum)Organic and chemical dusts (wood, cotton, platinum) – Chemicals (formaldehyde, penicillin products)

– After repeated exposureAfter repeated exposure – Mechanism

• Type I reactionyp

• Direct liberation of bronchoconstrictor substances

(76)

Role of Eosinophils in Asthma

:

Role of Eosinophils in Asthma

:

• release mediators (leukotrienes & PAF)

• produce

major basic protein (MBP)

of their

(77)

C, Priming or sensitization

Allergic Asthma

• Inhalated allergens (antigen) elicit a T_H 2-dominated response favoring IgE production and eosinophil recruitment

D, Re-exposure to antigen (Ag)

• The intermediate reaction is triggered by Ag-induced cross-linking of IgE bound to IgE receptors on mast cells in the airways. receptors on mast cells in the airways. • Release preformed mediators.

• directly or via neuronal reflexesdirectly or via neuronal reflexes

• the mediators induce bronchospasm,

increased vascular permeability, and mucus production

• recruit additional mediator-releasing cells from the blood

the blood.

E, The arrival of recruited leukocytes (neutrophils, eosinophils lymphocytes and monocytes) eosinophils, lymphocytes and monocytes) • initiation of the late phase of asthma and a

fresh round of mediator release from

leukocytes, endothelium, and epithelial cells. • Factors, particularly from eosinophils (e.g.,

j b i t i i hil ti i major basic protein, eosinophil cationic

(78)

3. Bronchial Asthma

Morphology

• Gross: overdistended due to

– overinflation : occlusion of bronchi and bronchioles

by thick tenacious mucous plugs

(79)

Bronchial Asthma

Histologic findings

g

:

(1) thickening of basement membrane of bronchial ep.

(2) edema and inflammatory infiltrates, esp. eosinophils in

bronchial walls

bronchial walls,

(3) increase in size of submucosal mucous glands

(4) hypertrophy of bronchial wall muscle

( ) yp

p y

lumen

(80)

Comparison of a normal bronchiole with Comparison of a normal bronchiole with that in a patient with asthma.

• Note the accumulation of mucus in the bronchial l lti f i i th b f lumen resulting from an increase in the number of mucus-secreting goblet cells in the mucosa and hypertrophy of submucosal mucus glands.

• In addition, there is intense chronic inflammation due to recruitment of eosinophils, macrophages, and other inflammatory cells

inflammatory cells.

• Basement membrane underlying the mucosal

epithelium is thickened, and there is hypertrophy and hyperplasia of smooth muscle cells.

(81)

Micro

:

Bronchial Asthma

Micro

:

Mucus plugs - whorls of shed epithelium

“

C

h

'

i l ”

“

Curschmann's spirals”

Crystalloids made of eosinophil membrane

protein

(82)

Bronchiectasis (기관지확장증)

(

)

Definition

• 기관지와 세기관지가 만성 괴

사성 감염으로 기관지의 근육

사성 감염

기관지의

육

과 탄력지지조직이 파괴되어

영구적으로 확장되는 것을 말

한다

_.

Etiology and Pathogenesis

Ob

i

d i f

i

f

• Obstruction and infection of

airways

(83)

Bronchiectasis

Associated with following conditions:

1 Bronchial obstruction 1. Bronchial obstruction

– Foreign bodies, mucous impaction, tumor – Localized to the obstructed lung segment

2. Congenital or hereditary conditions

– Congenital bronchiectasis – Cystic fibrosis (낭성 섬유증):

• defect in ion transport Æ defective mucociliary action and accumulation of thick viscid secretionsdefect in ion transport Æ defective mucociliary action and accumulation of thick viscid secretions

– Intralobar sequestration – Immunodeficiency states

• susceptibility to repeated bacterial infections

Immotile cilia (Kartagener's) syndromes – Immotile cilia (Kartagener s) syndromes

• structural abnormality of cilia : absent or irregular dynein arms

3. Postinfectious conditions

– Bacteria (Mycobacterium tuberculosis, Staphylococcus aureus, Haemophilus influenzae, Pseudomonas)

– Virus (Adenovirus, influenza virus, human immunodeficiency virus (HIV)

– Fungus (Aspergillus species)

Æ N ti i i (괴사성 폐렴)이 선행

Æ Necrotizing pneumonia (괴사성 폐렴)이 선행

(84)

Primary ciliary dyskinesia

• Autosomal recessive syndrome • 1 / 15,000 ~ 40,000 births

(

• Absence or shortening of the dynein arms (coordinated bending of cilia)

• Poorly functioned cilia Æ retention of secretion and recurrent y infections Æ bronchiectasis

“K d ”

• “Kartagener syndrome”

– ½ of primary ciliary dyskinesia – Bronchietasis

– Sinusitis

– Situs invertus or partial lateralizing abnormality

• Male: infertility (as a result of sperm dysmotility) • Male: infertility (as a result of sperm dysmotility)

(85)

Allergic BronchoPulmonary Aspergillosis (ABPA)

• Result from a hypersensitivity reaction to the fungus

Aspergillus

fumigatus

• An important complication of asthma and cystic fibrosis • High serum IgE level, serum antibodies to Aspergillus • Intense airway inflammation with eosinophils

• Formation of mucus plugs

• A relative deficiency of anti inflammatory cytokines (IL 10) • A relative deficiency of anti-inflammatory cytokines (IL-10) • Periods of exacerbation and remission, clinically, y

(86)

Absent dynein arms Ab t ik Absent spikes Transposition of doublets Normal 9+2 arrangement

(87)

4. Bronchiectasis

– 양측 하엽, 특히 기도가 좀더 수직인 우하엽 에 잘 발생한다.

• Gross

– 기도 확장

기

확

– Cylindroid (원통형), fusiform (방추

형

), saccular (주머니)

• Micro

:

1 기관지와 세기관지 벽에 급만성 염

1. 기관지와 세기관지 벽에 급만성 염

증 삼출액

2. 상피탈락

괴사성 괘양

3. 괴사성 괘양

4. 기관지와 세기관지의 섬유화와 주

위실질의 섬유화

5. 폐농양

(88)

Clinical course of Bronchiectasis

• Causes severe, persistent cough

• Expectoration of foul-smelling, sometimes bloody sputum • Dyspnea and orthopnea in severe cases

• Occasional life-threatening hemoptysisOccasional life threatening hemoptysis

• A systemic febrile reaction may occur when powerful pathogens are present.

are present.

• In the full-blown case, the cough is paroxysmal in nature.

– Such paroxysms are particularly frequent when the patient rises inSuch paroxysms are particularly frequent when the patient rises in the morning, and changes in position lead to drainage into the bronchi of the collected pools of pus.

• Cor pulmonale, metastatic brain abscesses, and amyloidosis are less frequent complications