경희대학교 의과대학·의학전문대학원

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(1)

Acute Lung Injury

Acute Lung Injury

(

• A spectrum of pulmonary lesions (endothelial and

epithelial), initiated by numerous factors

1. Pulmonary edema (폐부종)

2. Acute respiratory distress syndrome, ARDS, 급성호

흡곤란증후근 (diffuse alveolar damage DAD)

흡곤란증후근 (diffuse alveolar damage, DAD)

3

A

t i t

titi l

i (AIP) 급성간질성폐렴

3. Acute interstitial pneumonia (AIP), 급성간질성폐렴, =

“Hamman-Rich Syndrome”

(2)

Classification and Causes of Pulmonary Edema

• Hemodynamic Edema

– Increased hydrostatic pressure (increased pulmonary venous pressure)

• Left-sided heart failure (common) V l l d

• Volume overload

• Pulmonary vein obstruction

– Decreased oncotic pressure (less common)

• Hypoalbuminemia • Nephrotic syndromep y • Liver disease

• Protein-losing enteropathies

– Lymphatic obstruction (rare)

• Edema Due to Microvascular Injury (Alveolar Injury)

– Infection: pneumonia, septicemia – Inhaled gases: oxygen, smoke

– Liquid aspiration: gastric contents, near-drowningLiquid aspiration gastric contents, near drowning

– Drugs and chemicals: chemotherapeutic agent (bleomycin), other medications (amphotericin B), heroin, kerosene, paraquat

– Shock, trauma – Radiation

– Transfusion related

• Edema of Undetermined Origin

– High altitudeHigh altitude

(3)

Pulmonary Edema (폐부종)

y

(

)

• Hemodynamic (or Cardiogenic) pulmonary edema

(1) Increased hydrostatic pressure (most common)

• occurs in left sided congestive heart failure • occurs in left sided congestive heart failure

(2) Heavy, wet lung

(3) initially in the basal regions of the lower lobes (∵greater h d t ti )

hydrostatic pressure) (4) Histologically g y

• Engorgement of alveolar capillaries • Intraalveolar granular pink precipitate

• Alveolar microhemorrhages and hemosiderin-ladenAlveolar microhemorrhages and hemosiderin laden macrophages (Heart failure cells)

• 이 상태가 오래 지속되면 폐사이질은 섬유화가 진행되고 혈철소를 포함하고 있어 갈색조를 나타내는 갈색경화 (brown induration)가 일어난다.

(4)

Heart failure cells

Heart failure cells

(5)

Pulmonary Edema

y

Edema caused by microvascular injury

y

j y

(1) Injury to the capillaries of alveolar septa

(2) Usually not elevated pulmonary capillary

hydrostatic pressure

hydrostatic pressure

(3) primary injury to the vascular endothelium or

damage to alveolar epithelial cell

→ 이차적으로 microvascular injury유발

→ fluid와 protein이 interstitial space로 유출와 p 이 p 유출 → 더 심하면 폐포로까지 유출

→ 국소적일 땐 폐렴 유발, 미만성일 땐 ARDS (acute respiratory distress syndrome) 유발p y y ) 유

(6)

Adult Respiratory Distress Syndrome

(Diff

Al

l

D

)

(Diffuse Alveolar Damage)

Synonyms:

– Adult respiratory failure – Shock lung

Diffuse alveolar damage (DAD) – Diffuse alveolar damage (DAD) – Acute alveolar injury

– Traumatic wet lung

Definition

(1) Diffuse alveolar capillary damage에 의해 생긴 syndrome (1) Diffuse alveolar capillary damage에 의해 생긴 syndrome (2) Clinically, rapid onset of severe life-threatening respiratory

insufficiency, cyanosis, and severe arterial hypoxia that is f t t th

refractory to oxygen therapy

(3) may progress to extrapulmonary multisystemic organfailure

(4) 대부분의 경우 심한 폐부종이 있다 (x-ray상 diffuse alveolar

( ) ( y

(7)

Conditions Associated with Development of

A

t R

i t

Di t

S

d

(ARDS)

Acute Respiratory Distress Syndrome (ARDS)

• Infection • Chemical Injury

• Infection

– Sepsis*

– Diffuse pulmonary infections*

• Viral, Mycoplasma, and Pneumocystis

pneumonia; miliary tuberculosis

j y

– Heroin or methadone overdose – Acetylsalicylic acid

– Barbiturate overdose – Paraquat

– Gastric aspiration*

• Physical/Injury

– Mechanical trauma, including head

q

• Hematologic Conditions

– Multiple transfusions

– Disseminated intravascular

Mechanical trauma, including head injuries*

– Pulmonary contusions – Near-drowning

– Fractures with fat embolism

Disseminated intravascular coagulation (DIC) • Pancreatitis – Burns – Ionizing radiation • Inhaled Irritants • Uremia • Cardiopulmonary Bypass Inhaled Irritants – Oxygen toxicity – Smoke

– Irritant gases and chemicals

• Hypersensitivity Reactions

– Organic solvents – DrugsDrugs

(8)

Pathogenesis of ARDS (DAD)

g

(

)

• Acute lung injury (Morphologic and physiologic

Acute lung injury (Morphologic and physiologic

alteration)

– Capillary endothelial (most frequently) and alveolarCapillary endothelial (most frequently) and alveolar epithelium (occasionally)

ÆDamage to alveolar capillary membrane

ÆIncreased vascular permeability and alveolar flooding loss of ÆIncreased vascular permeability and alveolar flooding, loss of

diffuse capacity, and widespread surfactant abnormality (due to damage to type II pneumocytes)

ÆExudate and diffuse tissue destruction

Æ cannot easily resolved Æ organization with scarring Æ Æ cannot easily resolved Æ organization with scarring Æ

(9)

Pathogenesis of ARDS (DAD)

g

(

)

Acute insult (cellular event)

– Pulmonary macrophages Æ increased synthesis of IL-8 (potent neutrophil chemotactic and activating agent), IL-1

d TNF and TNF

Æ leads to pulmonary microvascular sequestration and p y q activation of neutrophils

(Neutrophils are thought to play an important role in the pathogenesis of acute lung injury and ARDS.)

Ærelease a variety of products (oxidants, proteases, platelet-activating factor (PAF) and leukotrienes)

activating factor (PAF), and leukotrienes)

Æ active tissue damage and maintain the inflammatory cascade

(10)

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(11)

Morpholgy of ARDS (DAD)

(1) Acute stage

1) grossly heavy firm red and boggy 1) grossly heavy, firm, red and boggy

2) congestion, interstitial and intra-alveolar edema, and inflammation

3) fibrin deposition 3) fibrin deposition

4) Waxy hyaline membrane lining alveolar wall

: 구성 성분

• fibrin rich edema fluid • fibrin rich edema fluid

• necrotic epithelial cell의 cytoplasmic and lipid remnants

(2) O

i i

(2) Organizing stage

1) type II epithelial cells proliferation

2) resolution은 드물고 보다 흔하게는 fibrin exudate의) organization이 일어남 → intra-alveolar fibrosis

3) → marked thickening of the alveolar septa, caused by proliferation of interstitial cells and deposition of collagen 4) 치명적인 경우는 종종 bronchopneumonia가 동반해서 발생함

(12)

Diffuse alveolar damage (acute respiratory distress syndrome) • Some of the alveoli are collapsed; others are distended.Some of the alveoli are collapsed; others are distended.

• Many contain dense proteinaceous debris, desquamated cells, and hyaline membranes (arrows).

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(13)

DAD

A

(14)

Clinical Courses of ARDS (DAD)

Clinical Courses of ARDS (DAD)

• 심한 dyspnea & tachypnea, 그러나 초기 chest x-ray는 정상소견을 보임 i i i & h i i t f il diff bil t l i filt ti

→ increasing cyanosis & hypoxemia, respiratory failure, diffuse bilateral infiltration on x-ray

• Hypoxemia

– unresponsible to oxygen therapy – respiratory acidosis can develop

– 치료를 위한 고농도의 산소가 또한 oxygen toxicity를 유발한다.

• Usual cause of death : respiratory failure or mulitiorgan dysfunction – ARDS의 사망률 : 60% in United States

• 폐가 functionally inhomogeneous focally stiff and decrease in functional volume폐가 functionally inhomogeneous, focally stiff and decrease in functional volume – infiltrated, consolidated or collapsed and nearly normal area

– 정상 폐에서는 aeration이 안 되는 지역으로는 perfusion이 안되지만, ARDS에서 환기불량부 위로 지속적 혈행 지속 → 환기-관류 부조화 (ventilation-perfusion mismatch) & 저산소증 (hypoxemia) 심화

• Nitric oxide (산화질소, NO)를 주면 전신순환계의 혈관저항과 혈압에는 영향을 주지

(15)

Acute Interstitial Pneumonia

(Hamman Rich Syndrome)

(Hamman-Rich Syndrome)

• A clinicopathologic term that is used to describe widespreadA clinicopathologic term that is used to describe widespread acute lung injury with a rapidly progressive clinical course similar to that seen in ARDS

• Unknown etiology

(cf. ARDS: associated with known causes such as sepsis, pulmonary infection, gastric aspiration, and trauma)

• The radiographic and pathologic features are identical to that of ARDS

• Mean age (50 years), no sex predilection

• Following an illness of less than 3 weeks' duration • The mortality rate is about 50% (within 1 to 2 months)

• In the surviving patients, recurrences and chronic interstitialIn the surviving patients, recurrences and chronic interstitial disease may develop

(16)

DISEASES OF VASCULAR ORIGIN

DISEASES OF VASCULAR ORIGIN

Pulmonary Embolism, Hemorrhage and Infarction Pulmonary Hypertension

(17)

Pulmonary Embolism and Infarction

Pulmonary Embolism and Infarction

1 pulmonary emboli의 95%는 leg의 deep vein

1. pulmonary emboli의 95%는 leg의 deep vein

thrombus에서 옴. 성인의 급사원인이 됨.

2. 원인

(1) 다른 underlying disorders

(1) 다른 underlying disorders

– cardiac disease, cancer, 오랫동안 움직이지 못하는 환자

(2) hypercoagulable state → deep vein thrombosis유발

(2) hypercoagulable state

deep vein thrombosis유발

• primary :

– antithrombin III or protein C deficiency d f ti fib i l i

– defective fibrinolysis

– presence of lupus anticoagulant

• Secondary

(18)

Pulmonary Embolism and Infarction

Pulmonary Embolism and Infarction

3 Morphology

3. Morphology

(1) depends on

• size of the embolic mass

• general status of the circulation

(2) 큰 emboli의 경우 혈류를 막는 것 자체 또는 acute cor l l 로 급사유발

pulmonale로 급사유발

(3) cardiovascular function이 좋은 경우 bronchial a.만으로도 폐 실질이 유지됨, 이런 경우 출혈은 일어나지만 infarction은 일어 나지 않음 나지 않음 (4) emboli의 10%만이 infarction유발 (5) i f ti 일어나는 경우는 이미 폐나 심장의 질환이 있는 경우 (5) infarction일어나는 경우는 이미 폐나 심장의 질환이 있는 경우 가 흔하다. 따라서 젊은이에게는 pulmonary infarction은 드물다. (6) l l b 에 주로 발생(3/4) 주로 lti l l i (>1/2)

(19)

Morphology of 폐경색

p

gy

1) 막힌 혈관을 첨점으로 쇄기모양으로 발생 1) 막힌 혈관을 첨점으로 쇄기모양으로 발생 2) classically hemorrhagic infarction

3) early stage : raised red-blue area

) 폐경색부위를 둘러싸는 흉막은 덮임

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 10 September 2006 08:59 AM) © 2005 Elsevier 4) 폐경색부위를 둘러싸는 흉막은 fibrinous exudate로 덮임 5) 적혈구가 48시간내에 분해되어 hemosiderin이 침착됨에 따라 폐경 색부위는 red- brown 색을 띔 6) 시간이 지나면서 주변부부터 섬유화로 대체되어 주변부가 6) 시간이 지나면서 주변부부터 섬유화로 대체되어 주변부가 gray-white색을 띄고 마침내는 전체 경색부위가 위축된 scar tissue로 대 치됨

7) acute pulmonary infarction의 조직학적 특징:

– 출혈소견을 보이는 조직 내에 ischemic necrosis가 관찰됨 (affecting the alveolar walls bronchioles and vessels)

the alveolar walls, bronchioles, and vessels)

8) infected embolus → septic infarcts (neutrophilic exudation, intense inflammatory reaction) → convert to abscess

(20)

Pulmonary Embolism and Infarction

Pulmonary Embolism and Infarction

4 pathophysiologyic response and clinical significance

4. pathophysiologyic response and clinical significance

에 관여하는 factors

(1) pulmonary blood flow obstruction 정도 (2) 막힌 혈관의 크기

(2) 막힌 혈관의 크기 (3) number of emboli

(4) over all status of cardiovascular system

(5) l f ti f t ( th b A2) (5) release of vasoactive factors ( e.g. thromboxan A2) ←

platelet

5. Emboli → two main pathophysiologic consequence

(1) respiratory compromise : non perfused but ventilated segment g

(2) hemodynamic compromise

: increased resistance to pulmonary blood flow → pulmonary hypertension pulmonary hypertension

(21)

Pulmonary Embolism and Infarction

Pulmonary Embolism and Infarction

6. Large emboli → 급사유발, electromechanical dissociation (EKG 6. Large emboli 급사유발, electromechanical dissociation (EKG

상 rhythm은 보이지만 pulse가 안 잡힘)

Large saddle embolus from the femoral vein lying astride the main

f

left and right pulmonary arteries

.

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(22)

Pulmonary Embolism and Infarction

Pulmonary Embolism and Infarction

6. Large emboli → 급사유발, electromechanical dissociation (EKG 6. Large emboli 급사유발, electromechanical dissociation (EKG

상 rhythm은 보이지만 pulse가 안 잡힘) 7. Small emboli

(1) normal cardiovascular system → transient chest pain, cough,

( ) y p , g ,

pulmonary hemorrhage without infarction

(2) inadequate cardiovascular system → dyspnea, tachypnea, fever, chest pain, cough, hemoptysis → small infarct

8. Chest x-ray : wedge shaped infiltrate in 12~36hrs 9. Angiography가 가장 정확하지만 위험

10. emboli는 시간이 지나면서 contraction과 fibrinolysis를 거쳐

resolve되지만 (특히 젊은이들의 경우), unresolved multiple small emboli는 pulmonary hypertension pulmonary vascular sclerosis emboli는 pulmonary hypertension, pulmonary vascular sclerosis, chronic cor pulmonale를 유발시킨다.

11. underlying predisposing factor가 있을 때 pulmonary embolus있 었던 경우 30%에서 또 다시 pulmonary embolus 발생함

(23)

Pulmonary Hypertension

Pulmonary Hypertension

• 정상적으로 폐순환은 혈류저항이 낮아 폐혈관의

압력은 체순환 압력의 1/8 정도이다.

• 폐 혈관 압력이 체순환 압력의 ¼ 수준에 이르면

폐고혈압이 생긴 것을 의미한다

폐고혈압이 생긴 것을 의미한다.

원인

• 원인

– Most frequently, secondary

– Uncommonly primary or idiopathic

Uncommonly, primary or idiopathic

• Sporadic – most commonly • Familial form – 6%

O l 10 20% t ll d l t di

(24)

Pulmonary Hypertension

Pulmonary Hypertension

• 이차적 (Secondary) 원인

– ↑ pulmonary blood flow or pressure (or both) – ↑ pulmonary blood flow or pressure (or both) – ↑ pulmonary vascular resistance

– ↑ left heart resistance to blood flow

(1) Chronic obstructive or interstitial lung disease (COPD or CILD)

: 저산소증, 폐실질파괴 → 폐포모세혈관 수적인 감소 → 폐동맥저항의 증가 → 폐혈압상승

(2) Antecedent congenital or acquired heart disease

: MS (mitral stenosis) → ↑Lt atrial pressure → ↑pulmonary v. pressure

↑ l

→ ↑pulmonary a. pressure

(3) Recurrent thromboemboli

→ ↓ functional cross-sectional area of pulmonary vascular bed → → ↓ functional cross sectional area of pulmonary vascular bed →

↑pulmonary a. resistance→ ↑pulmonary a. pressure

(4) Autoimmune disorder

• “Systemic sclerosis” Æ inflammation, intimal fibrosis, medial hypertrophy, and pulmonary hypertension

(25)

Pathogenesis of Pulmonary Hypertension

z Primary pulmonary hypertension

™In vascular smooth muscle cells, BMPR2 (bone

morphogenic protein receptor type 2) signaling

causes inhibition of proliferation and favors

causes inhibition of proliferation and favors

apoptosis

¾ Inactivating germ line mutations of BMPR2 gene

• 50% of familial • 26% of sporadicp

¾ Modifier genes

i

l i

(26)

Pathogenesis of Pulmonary Hypertension

z Secondary pulmonary hypertension

1) Endothelial cell dysfunction - 가장 중요한 역할을 함

(1) shear(전단력) 증가 & mechanical injury ← eg.) left-to-right shunt (2) biochemical injury ← fibrin in thromboembolism

2) ① prostacyclin 감소, ② nitric oxide (NO) 감소, ③ endothelin 증가

(1) ①, ②, ③ → pulmonary vasoconstriction

( ) ① ② ↑

(2) ①, ② → ↑platelet adhesion & activation

(3) endothelial activation → ↑ endothelial cell thrombogenic, ↑ persistence of fibrin

(4) ↑growth factor, cytokine → vascular smooth muscle cells 증가 및 이동,

( ) ↑g , y ,

extracellular matrix 생성

3) 기타 식물이나 약품도 pulmonary hypertension 유발

(1) 식품 C t l i t bili (열대지방 콩과식물 t 로 음용)

(1) 식품- Crotalaria spectabilis (열대지방 콩과식물, tea로 음용) (2) 약제

– 식욕억제제 : aminorex & 불순물이 섞인 올리브유 – Antiobesity drug : fenfluramine & pentermine

(27)

Morphology of Pulmonary Hypertension

1. Organizing or recanalized thrombi

: recurrent pulmonary emboli가 원인임을 시사

2 Diffuse pulmonary fibrosis severe emphysema 2. Diffuse pulmonary fibrosis, severe emphysema

and chronic bronchitis의 동반

: chronic hypoxia가 시발점임을 시사 3. 전체 폐동맥에 모두 변화가 올 수 있다. 1) Large artery • 심한 경우, systemic atherosclerosis에서와 같은 atheromatous deposit (죽종)을 볼 수 있다 atheromatous deposit (죽종)을 볼 수 있다.

2) 40-300㎛ 정도의 small artery (소동맥)과 Arteriole (세동맥)에서 가장 현저한 변화를 보인다.

• medial muscular thickening (medial hypertrophy), intimal fibrosis

intimal fibrosis

• 이러한 변화는 primary일 때 가장 현저하다.

3) Plexogenic pulmonary arteriopathy (tuft of cellular capillary formation)

• Advanced (one extreme in the spectrum ofAdvanced (one extreme in the spectrum of pathologic changes)

• mostly prominently in primary pulmonary

hypertension or congenital heart disease with left-to-right shunt

4) C it l h t di 의 치료방침을 결정하는데

4) Congenital heart disease의 치료방침을 결정하는데 pulmonary hypertensive vascular abnormality의 정 도가 중요하다.

(28)

Clinical Course of Pulmonary Hypertension

Secondary의 경우 아무 나이에나 다 생길 수 있지만,

Primary의 경우 20 40대 여성에서 가장 흔하다

Primary의 경우 20-40대 여성에서 가장 흔하다.

Clinical symptom and sign 등은 질환이 상당히 진전

Clinical symptom and sign 등은 질환이 상당히 진전

된 뒤에나 나타난다.

– Dyspnea, fatigue, anginal type chest pain → severe

respiratory distress, cyanosis, Rt. ventricular hypertrophy respiratory distress, cyanosis, Rt. ventricular hypertrophy

Death :

80%의 환자가 2 5년내 d d l l – 80%의 환자가 2-5년내 decompensated cor pulmonale,

superimposed thromboembolism & pneumonia 등으로 사망

치료 :

– Vasodilator (calcium channel blocker, inhaled nitric oxide) – Antithrombotics (warfarin prostacyclin thromboxaneAntithrombotics (warfarin, prostacyclin, thromboxane

(29)

Diffuse Pulmonary Hemorrhage Syndromes

Diffuse Pulmonary Hemorrhage Syndromes

(광범위 폐출혈 증후군)

• Goodpasture SyndromeGoodpasture Syndrome

• Idiopathic Pulmonary Hemosiderosis • Vasculitis-associated hemorrhage

(30)

Goodpasture Syndrome

Goodpasture Syndrome

U

t i

di

• Uncommon autoimmune disease

Characterized by the presence of circulating

• Characterized by the presence of circulating

autoantibodies (IgG subtype) targeted against the

noncollagenous domain of the α

g

33

chain of collagen IV

g

– The antibodies initiate an inflammatory destruction of the basement membrane in kidney glomeruli and lung alveoli

• 급진행 사구체신염 (Rapidly Progressive Glomerulonephritis,급진행 사구체신염 (Rapidly Progressive Glomerulonephritis, RPGN)

• 괴사 출혈 사이질 폐렴 (Necrotizing hemorrhagic interstitial pneumonitis)

(31)

Morphology of Goodpasture Syndrome

Morphology of Goodpasture Syndrome

• Gross:

– Heavy lung with areas of red-brown

consolidation

• Micro:

Micro:

– focal necrosis of alveolar walls

associated with intra-alveolar

associated with intra alveolar

hemorrhage

– Later stage:

g

• Fibrous thickening of septae

• Hypertrophy of type II pneumocytes

Acute intra-alveolar

hemorrhage and hemosiderin-laden macrophages, reflecting previous hemorrhage, are common features of the

• Organization of blood in alveolar spaces common features of the diffuse pulmonary hemorrhage syndromes (Prussian blue stain for iron).

(32)

Morphology of Goodpasture Syndrome

Morphology of Goodpasture Syndrome

• Immunofluorescence (면역형광)

• Immunofluorescence (면역형광)

study

– Lung: • Linear deposits of i l b li l b t

immunoglobulins along basement membrane of the septal walls

– Kidney:

• Linear deposits of

immunoglobulins and complement immunoglobulins and complement along the glomerular basement membranes

(33)

Clinical Course of Goodpasture Syndrome

Clinical Course of Goodpasture Syndrome

• Clinically begin with respiratory symptoms (hemoptysis) andClinically, begin with respiratory symptoms (hemoptysis) and radiographic evidence of focal pulmonary consolidations

• Soon, glomerulonephritis appear, leading to rapidly progressive renal failure

• Common cause of death: uremia (요독증) • Treatment:

– Plasma exchange (혈장교환)

• Removing circulating antibasement membrane antibodies and chemical Removing circulating antibasement membrane antibodies and chemical mediators of immunologic injury

– Immunosuppressive therapy (면역억제제)

i hibit f th tib d d ti • inhibit further antibody production

Æ Both the lung hemorrhage and the glomerulonephritis improve with this form of therapy

(34)

Idiopathic Pulmonary Hemosiderosis

(특발 폐혈철증)

A di d h i d b I i diff l l • A rare disorder characterized by Intermittent, diffuse alveolar

hemorrhage

U ll t ith i idi t f d ti h • Usually, present with an insidious onset of productive cough,

hemoptysis, anemia, and weight loss

M t i hild lth h th di h b

• Most cases occur in children, although the disease has been reported in adults as well.

C d th i k

• Cause and pathogenesis : unknown • No antibasement membrane antibody • Immunologic mechanism?

– Favorable response to long-term immunosuppression with predisone and/or azathioprine

(35)

Morphology of Idiopathic Pulmonary

Hemosiderosis

Hemosiderosis

• Gross:

Gross

– Moderately increased in weight, with areas of

consolidation (red-brown to red)

• Micro:

– Hemorrhage into the alveolar spaces

– Hemosiderosis, within the alveolar septa and in

macrophages

– Type II pneumocytes hyperplasia

V

i

d

f i t

titi l fib

i

– Varying degrees of interstitial fibrosis

– No vasculitis, capillaritis, or inflammatory

infiltration

(36)

Pulmonary Vasculitis

• Inflammation of pulmonary vessel walls

• A part of a more generalized disease or Alone

(A) vessel-associated inflammation (B) true vasculitis. Note the disruption of the media by inflammatory cells in true vasculitis

(37)
(38)

Chapel Hill Consensus Conference 1992

Nomenclature of Systemic Vasculitis

Nomenclature of Systemic Vasculitis

• Large or elastic artery :

– Aorta & innominate a subclavian common carotid iliac pulmonaryAorta & innominate a, subclavian, common carotid, iliac, pulmonary

• Giant cell (temporal) arteritis • Takayasu arteritis

• Medium-sized or muscular artery :Medium sized or muscular artery

– Coronary or renal artery

• Polyarteritis nodosa (classic polyarteritis nodosa) • Kawasaki disease

• Small artery

– <2 mm in diameter

– within the substance of tissue & organ

W ’ l i (WG)

• Wegener’s granulomatosis (WG)

Microscopic polyangiitis (MPA) ANCA-associated • Churg-Strauss syndrome (CSS)

• Behçet’s diseaseBehçet s disease

• Henoch-Schönlein purpura

• Vasculitis asso with SLE, RA, Sjogren’s syndrome • Cryoglobulinemic vasculitis

• Goodpasture’s syndrome

(39)

Antineutrophil cytoplasmic antibody (ANCA)

: heterogenous autoAb against enzymes

in azurophil or primary granules of

neutrophils & in lysosomes of

monocytes and endothelial cells

(1) Cytoplasmic (c-ANCA);

– The most common target Ag은 neutral leukocyte protease (proteinase 3 PR-3) leukocyte protease (proteinase 3, PR-3) – Wegener's granulomatosis (WG)

(2) perinuclear (p-ANCA)

– specific for myeloperoxidase (MPO)specific for myeloperoxidase (MPO) – Microscopic polyangiitis (MPA)

Ch St d (CSS) – Churg-Strauss syndrome (CSS)

(40)

Wegener’s Granulomatosis (WG)

Wegener s Granulomatosis (WG)

• Definition

• Definition

– Systemic necrotizing granulomatous vasculitis of

unknown etiology

• Incidence

(

)

– Rare (0.3 per million persons in USA)

– Most common systemic vasculitis to involve the

lung

lung

– The most common ANCA-associated vasculitis

• Mean age of onset: 45 years, M:F = 1~2:1

• No racial predilection

(41)

Wegener’s Granulomatosis (WG)

• Classic triad (Godman and Churg, 1954)

– Necrotizing granulomatous inflammation of the upper and/or lower respiratory tract

G li d liti i l i t i d i

– Generalized vasculitis involving arteries and veins – Focal necrotizing glomerulonephritis

• Clinically characterized by

– Upper airway involvementpp y

• Sinusitis (purulent or bloody discharge, mucosal drying and crust

formation), ulcerations, bony deformities, otitis, subglottic or bronchial stenosis

– Lower respiratory tract involvement

• Cough, chest pain, shortness of breath, hemoptysis

Glomerulonephritis – Glomerulonephritis

(42)

Wegener’s Granulomatosis (WG)

Wegener s Granulomatosis (WG)

Clinical findings in 158

1

and 155

2

patients

Clinical findings in 158 and 155 patients

• Ear, nose and throat

• Lung involvement 92%85% 99%66% • Lung involvement • Renal involvement • Eye involvement • Skin involvement 85% 77% 52% 46% 66% 70% 61% 33% Skin involvement • Neuropathy • c-ANCA (+) 46% 15% 88% 33% 40% 84%

1 Hoffman et al, Ann Intern Med 1992

(43)

Radiographic Findings of WG

Radiographic Findings of WG

• 30 patients (Korea & Japan)

– Nodules or masses: 90%

– Nodules or masses: 90%

• Multiple in 85% (single, 15%)

• Bilateral in 67%

• Subpleural in 89%

– Abnormal large airways: 30%

Abnormal large airways: 30%

– Patchy consol & GGO: 23%

(44)

Gross findings of WG

• Dark (pulmonary hemorrhage)

• Solid nodular zones of consolidation with punctuate or

geographic necrosis

geographic necrosis

Å ti i l i it t d

(B) multiple scattered nodular foci of consolidation are present.

Å necrotizing granuloma is cavitated with a necrotic center and an

(45)

Diagnostic criteria of WG

Diagnostic criteria of WG

(46)

Vasculitis of WG

-Necrotizing granulomas involving adventitia and mediaNecrotizing granulomas involving adventitia and media.

-This narrowed vessel shows palisaded granulomas with basophilic necrosis accompanied by inflammation and fibrosis of the adventitia.

(47)

Elastic stain

Elastic stain

(A) disruption of the elastic lamina in

involved arteries. (B) Granuloma displacing elastic lamina and protruding into the vessel lumen

(48)

WEGENER’S GRANULOMATOSIS

(49)

The Granulomas of WG

“Cartwheel” pattern

(A) WG granulomas

- More “pallisaded” than those seen in (B) granulomatous infection.

(B) Tuberculosis granulomas -More epithelioid histiocytes g

- Blue (basophilic) appearance of the necrosis of WG

(50)

Prognosis and Therapy of WG

Prognosis and Therapy of WG

• Treatment

– Immunosuppressive drugs

• Corticosteroids

• Cyclophosphamide

– Response of treatment : 90%

– Complete remission : 75%

(51)

Allergic granulomatosis & angiitis

Churg-Strauss Syndrome (CSS)

• Definition

– Systemic disorders characterized asthma

Systemic disorders characterized asthma,

peripheral blood eosinophilia, and systemic

vasculitis

• Incidence

Occurs almost exclusively in patient with asthma

– Occurs almost exclusively in patient with asthma

or allergic rhinitis

– The true incidence of CSS in unclear

(52)

Churg-Strauss Syndrome

(CSS)

(CSS)

• Clinical features

Clinical features

– The diagnosis is clinical and must include at

least four of the following parameters:

least four of the following parameters:

1. Asthma

2

Peripheral eosinophilia (>10% of total WBC)

2. Peripheral eosinophilia (>10% of total WBC)

3. Neuropathy

4. Radiologic pulmonary infiltrates (non fixed)

4. Radiologic pulmonary infiltrates (non fixed)

5. Sinusitis

6. Evidence of extravasated eosinophils in tissues

• Diagnostic criteria

= Biopsy evidence of vasculitis +

≥ 4/6 criteria

= Biopsy evidence of vasculitis + ≥ 4/6 criteria

(53)

Churg-Strauss Syndrome (CSS)

Churg Strauss Syndrome (CSS)

Clinical findings in 96

1

and 91

2

patients

• Asthma

• Peripheral nerve

• Sinus

100%

76%

61%

99%

78%

74%

Sinus

• Skin

• Lung

• GI tract

61%

57%

38%

33%

74%

51%

58%

31%

• GI tract

• Kidney

• Heart

33%

26%

14%

31%

25%

13%

1 Guillevin et al, Medicine 1999 2 Keogh et al, Am J Med 2003

(54)

Progression of CSS

1. Prodromic phase

– Asthma ± allergic rhinitis

E i hili i i h l bl d – Eosinophilia in peripheral blood – Eosiniphilic tissue infiltrates

• Eosinophilic pneumonia • Gastrointestinal tractsGastrointestinal tracts

2. Vasculitic phase

S t i i d t

– Systemic sign and symptoms

• Neuropathy

• Cutaneous leukocytoclastic vasculitis

pANCA: 70% – pANCA: 70%

3. Post-vasculitic phase

– Neuropathy

– Cardiac involvement : 47 %

• cardiac failure, pericarditis, myocardial infarction

R l i l t l f t d l th i WG – Renal involvement : less frequent and less severe than in WG

(55)

Radiologic features of CSS

Radiologic features of CSS

• Multifocal parenchymal consolidation

that changes in location and

g

appearance

• Very often the consolidation shows a

peripheral distribution

(56)

Pathologic features of CSS

Pathologic features of CSS

G

• Gross

– Peripheral patchy nodular consolidation

– Cavitation is extremely rare

• Micro

– Depend on the phase of disease

Depend on the phase of disease

– Eosinophilic pneumonia, gastroenteritis, or

lymphadenitis are typical of the prodromic

y p

yp

p

phase

(57)

“Allergic granuloma” of CSS

• The vaguely palisaded histiocytes at the periphery of

eosinophilic necrosis (center).

• Multinucleated giant cells may occur and typically have

a brightly eosinophilic cytoplasm.

(58)

Vasculitis of CSS

• Vasculitis with fibrinoid necrosis, containing eosinophils, that affects small arteries, venules, and capillaries, is typical

A medium-sized artery infiltrated by A venule infiltrated by eosinophils.

A y y

eosinophils and scattered lymphocytes.

A y p

Note fibrin and eosinophils in surrounding airspaces.

(59)

Diffuse pulmonary hemorrahage with

ll

l

liti (

ill iti ) f CSS

(60)

Prognosis and therapy of CSS

Prognosis and therapy of CSS

• Generally has a good prognosis, but cardiac

and severe gastrointestinal involvement are

associated with a poor prognosis

associated with a poor prognosis

• Most patients with CSS shows a good response

Most patients with CSS shows a good response

to corticosteroids

• Cyclophosphamide is added in cases refractory

to corticosteroids or with involvement of more

than one organ system.

(61)

Microscopic Polyangiitis (MPA)

Microscopic Polyangiitis (MPA)

D fi iti

• Definition

– Necrotizing vasculitis that small vessels (arteriols,

venules and capillaries) with few or no immune

venules and capillaries) with few or no immune

complex deposits

I

id

• Incidence

– Rare (0.1 per million persons in USA)

• Peak incidence : fourth to sixth decades (mean

age: 56 yrs)

g

y )

• Slight female predominance (1.5:1)

• No racial predilection

(62)

Clinical features of MPA

Clinical features of MPA

M

t

f

l

l

d

• Most common cause of pulmonary-renal syndrome

• Major clinical characteristics

• Major clinical characteristics

– Glomerulonephritis dominates (90%) Alveolar hemorrhage (12~50%)

– Alveolar hemorrhage (12~50%) – p-ANCA(+) in 40~80%

• Most patient have a rapid onset of symptoms

• Systemic symptoms include arthralgias, myalgias,

fever, weight loss, dyspnea, hemoptysis, cough,

and chest pain

(63)
(64)

Radiologic findings of MPA

Bilateral alveolar opacities (alveolar hemorrhage)

without nodules (GGO)

(65)

Pathologic features of MPA

Pathologic features of MPA

G

• Gross

– Dark (due to pulmonary hemorrhage)

• Micro

– Neutrophilic capillaritis in a backgrund of hemorrhage

– No granulomatous inflammation

– Neutrophilic infiltrates may extend into the alveolar

space, mimicking acute pneumonia

– Fibrin deposition, hyaline membranes,

hemosiderin-laden macrophages, and organizing pneumonia may

be present

(66)

Alveolar hemorrhage with Capillaritis of MPA

g

p

• Common manifestation

• Fibrin and capillary disruption with neutrophils.

• Hemosiderin-laden macrophages in adjacent

(67)

WG CSS MPA

Asthma No Yes No

Asthma No Yes No

Eosinophilia Usually not Yes, high No

Tissue eosinophilia Rare Yes (eosinophilic No

Tissue eosinophilia Rare Yes (eosinophilic

pneumonia) No ANCA 60-95%, usually c-ANCA 50-70%, usually p-ANCA 70-80%, usually p-ANCA

ANCA ANCA ANCA

Radiologic findings Multiple, often bilateral, nodules,

Patchy airspace opacities, often

Bilateral diffuse airspace opacities

may cavitate transient

Glomerulonephritis Frequent Occasional, mild Usual

Necrotizing URT lesions Common No No N ti i Y ( t I l i N Necrotizing granulomatous inflammation Yes (except hemorrhagic and capillaritis variant) In classic cases only, often absent

No

Necrotizing vasculitis

Yes Yes Yes (capillaritis only)

(68)

PULMONARY INFECTIONS

(폐감염증)

(폐감염증)

• Bacterial Infection

• Viral Infection

Viral Infection

• Fungal Infection

• Parasite Infection

Parasite Infection

(69)

Bacterial Pneumonia (세균성 폐렴)

Bacterial Pneumonia (세균성 폐렴)

• 폐실질에 bacterial invasion → exudative solidification

(consolidation) (삼출경화)의 특징적인 병변을 만든다

(consolidation) (삼출경화)의 특징적인 병변을 만든다.

• 분류

분류

(1)Etiologic agents

• Pneumococcal pneumonia (폐렴사슬알균 폐렴) • Staphylococcal pneumonia (포도알균 폐렴)Staphylococcal pneumonia (포도알균 폐렴) • Klebsiella pneumonia (폐렴막대균 폐렴)…..

(2) Nature of host reaction (2) Nature of host reaction

• Suppurative pneumonia (화농 폐렴) • Fibrinous pneumonia (섬유소 폐렴)

(3) Gross anatomic distribution

• Lobular bronchopneumonia (소엽 or 기관지 폐렴) • Lobar pneumonia (대엽 폐렴)p

(70)

• Bronchopneumonia

– Gross section of lung showing patches of consolidation (arrows).

• Lobar pneumonia

• Lobar pneumonia

– Gray hepatization, – The lower lobe is

(71)

1 Pathogenesis

1. Pathogenesis

Th f t

f i h l d

ti l

d

d

th i

i

The fates of inhaled particles depend on their sizes.

〉10㎛ 〉 ㎛

→ deposited largely in the turbulent airway of the nose and upper airways

3~10㎛

→ lodge in the trachea and bronchi by impaction

1~5㎛

→ size of most bacteria, deposited in the terminal airways and alveoli

1㎛

(72)

Potent defense mechanism

1) nasal clearance

– 앞쪽 nonciliated epithelium에 deposit – 앞쪽 nonciliated epithelium에 deposit

→ sneezing and blowing

– 뒤쪽 nasopharynx의 mucus-lined ciliated epithelium에 deposit

→ swallowing g

2) tracheobronchial clearance – mucociliary (점액섬모) action

– cilia의 beating motion → film of mucus가 lung에서 oropharynx로cilia의 beating motion film of mucus가 lung에서 oropharynx로 → swallowing or expectoration

3) alveolar clearance - phagocytosis by alveolar macrophages ) p g y y p g

– digested

– carried to ciliated bronchioles → oropharynx → swallowing

– through interstitial space → bronchioles or lymphatics capillaries

4) particle이 무겁거나 macrophage transport가 어려운 경우

– regional lymph node로g y p

(73)

Defense mechanism을 저해하는 factors

1) loss or suppression of the cough reflex (기침반사)

• gastric content aspiration 일어날 수 있음

• coma, anesthesia, neuromuscular disorder, drugs, chest pain

2) injury to the mucociliary apparatus (점액섬모장치)

• impairment of ciliary function, destruction of ciliated epithelium

i tt ki h t i i l di ti

• cigarette smoking, hot or corrosive gas, viral disease, genetic disturbance (immotile cilia syndrome, 부동성섬모증후근)

3) alveolar macrophages의 phagocytic or bactericidal action의 저해 3) alveolar macrophages의 phagocytic or bactericidal action의 저해

• alcohol, tobacco smoke, anoxia, oxygen intoxication

4) pulmonary congestion and edema (폐울혈과 폐부종) 5) accumulation of secretion

• cystic fibrosis (낭성섬유증), bronchial obstruction

6) host의 면역방어기전이 저하된 상태

• chronic diseases, immunologic deficiency, treatment with

immunosuppressive agents, leukopenia, unusually virulent infections immunosuppressive agents, leukopenia, unusually virulent infections

(74)

2 Etiology

2. Etiology

(1) Bronchopneumonia (기관지폐렴): – Staphylococci (포도알균) – Streptococci (사슬알균) – Pneumococci (폐렴사슬알균) – Haemophilus influenzae (인플루엔자균) – Psuedomonas aeruginosa (녹농균) – Coliform bacteria (대장균) (2) Lobar pneumonia (대엽폐렴):

– 90~95%=pneumococci (Streptococcus pneumoniae, 주로 type 1, 2, 3 and 7) 3, and 7) – Klebsiella pneumoniae (폐렴막대균) – Staphylococci (포도알균) – Streptococci (사슬알균)Streptococci (사슬알균) – H. influenzae (인플루엔자균)

– Gram negative (Pseudomonas (녹농균), Proteus (프로테우스 막대균) bacilli

(75)

Bronchopneumonia (기관지폐렴)

Bronchopneumonia (기관지폐렴)

1) 기관지 주위의 폐실질에 여러 개의 작고 불규칙한 반상 경화 1) 기관지 주위의 폐실질에 여러 개의 작고 불규칙한 반상 경화 (patchy consolidation)를 특징으로 한다. 2) 대체로 기존의 기관지염 내지 세기관지염이 주위 폐실질로의 확 2) 대체로 기존의 기관지염 내지 세기관지염이 주위 폐실질로의 확 산에 기인한 것이다. 3) 염증성 삼출물이 중력에 의해 하엽으로 유입되어 주로 하엽에 분 포 4) 소아와 노인에서 잘 발생 5) 합병증 5) 합병증 – 폐농양, 농흉, 화농성 심막염, – 균혈증에 의한 다른 장기의 전이성 농양

(76)

Lobar pneumonia (대엽폐렴)

p

(대엽폐렴)

1) 한 엽의 거의 전부 또는 여러 개의 엽이 동시에 급성 세균감염을 받은 상태 받은 상태 2) 어느 연령층에서도 발생하지만, 소아와 노인에 비교적 드물다. 3) 원인균

– 90-95%는 pneumococci (Streptococcus pneumoniae)가 원인균이 며 type 3이 독성이 가장 강함

며 type 3이 독성이 가장 강함.

4) 병소 파급이 용이한 이유

– pore of Kohnpore of Kohn

• 울혈기에 다량의 장액삼출물이 분비되고 이들이 폐포와 폐포사이의 Korn

구멍을 통하여 엽전체로 파급되어 세균성장의 배지로 작용

– pneumococci는 copious mucoid encapsulation되어 있어서 탐식으 로부터 보호됨

로부터 보호됨

5) 20-25%에서 발생하는 균혈증은 심각한 합병증으로 뇌막염, 세균심 내막염 심낭염 또는 패혈관염으로 진행

(77)

Lobar pneumonia (대엽폐렴)

형태 : 일반적으로 4 stage

Lobar pneumonia (대엽폐렴)

형태 일반적 4 stage

1. stage of congestion (~24hrs), 울혈기 ① gross : heavy, boggy, red

② micro : vascular engorgement, intraalveolar fluid with few neutrophils, often presence of numerous bacteria

p

2. stage of red hepatization (1~3days), 적색 간변기 ① gross : red, firm, airless with liver-like consistency

② micro : massive confluent exudation with red cells (붉게 보인다) alveolar space내 ② micro : massive confluent exudation with red cells (붉게 보인다), alveolar space내

에 neutrophil과 fibrin이 찬다.

3. stage of gray hepatization (4~8days) ★, 회색간변기 ① gross : grayish brown dry surface

① gross : grayish brown, dry surface

② micro : alveolar space내에 fibrin이 축적, progressive disintegration of red cell, persistence of fibrosupprative exudate

4 stage of resolution (융해기) 4. stage of resolution (융해기)

: alveolar space내의 consolidated exudate가 progressive enzymatic digestion → granular, semifluid debri

(78)

A, Acute pneumonia.

– The congested septal capillariesThe congested septal capillaries and extensive neutrophil

exudation into alveoli corresponds to early red hepatization.

– Fibrin nets have not yet formed.

B, Early organization of

intra-alveolar exudate, seen in areas to be streaming through the g g pores of Kohn (arrow).

C, Advanced organizing

pneumonia (corresponding to gray hepatization)

gray hepatization)

– transformation of exudates to fibromyxoid masses richly

infiltrated by macrophages and infiltrated by macrophages and fibroblasts.

(79)

Complications of Bacterial Pneumonia

Complications of Bacterial Pneumonia

1) Ab

f

ti

1) Abscess formation

← tissue destruction and necrosis (type3 pneumococci, Klebsiella)

2) Empyema (intrapleural fibrinosuppurative reaction) 농

← spread to pleural cavity

3) Organization of the exudate

3) Organization of the exudate

4) Bacteremic dissemination

– heart valve, pericardium, brain, kidney, spleen, joint

→ metastatic abscess, endocarditis, meningitis, suppurative arthritis

(80)

Legionella Pneumonia

Legionella Pneumonia

원인균

• 원인균: Legionella pneumophilia

– 그람음성막대균 또는 알막대균

– 집, 호텔, 병원 등에 있는 물탱크 속에서 번식

하여 기도를 통하여 감염

– 특히, 환기가 잘 되지 않는 샤워실이 주 감염

• 노인 면역억제자 만성 알코올중독자 또

• 노인, 면역억제자, 만성 알코올중독자 또

는 악성 종양환자에서 호발한다.

(81)

Legionella Pneumonia

Legionella Pneumonia

병리소견:

• 병리소견:

– 무겁고, 섬유소 또는 섬유소-화농성흉막염을 잘 동반,

대엽폐렴과 비슷한 형태를 보인다.

대엽폐렴과 비슷한 형태를 보인다.

– 초기에는 광범위한 출혈성부종

Æ 삼출액이 폐포강과 원위부 세기관지를 채움

• 많은 수의 단핵구에 의해 둘러싸인 호중구의 파괴 (백혈구파 괴증, leukocytoclasis)가 특징이다.

– 회복기에는 폐포중격의 사이질내에 단핵세포가 침윤

되면서 사이질 섬유화가 진행

되면서 사이질 섬유화가 진행

Æ 광범위한 섬유화에 의해 폐포와 세기관지의 폐쇄가

초래

(82)

폐결핵 (Pulmonary Tuberculosis)

폐결핵 (Pulmonary Tuberculosis)

• Mycobacterium

Mycobacterium

– Slender, aerobic rods, non-spore-forming, non-motile bacilli with waxy coat

• Waxy cell wall (mycolic acid로 구성)*; • Waxy cell wall (mycolic acid로 구성)*;

– Acid fast

» to retain the red dye when treated with acid and alcohol in the acid-fast stains.

• Two species of

Mycobacterium

cause tuberculosis

M t b l i (인형) – M. tuberculosis (인형) *

• transmitted by inhalation of infective droplets coughed or sneezed into the air by a patient with tuberculosis.

– M. bovis (우형) *

• transmitted by milk from diseased cows Æ intestinal or tonsilar lesion

(83)

• Characteristic tubercle at low magnification ( A) and in detail ( B), toCharacteristic tubercle at low magnification ( A) and in detail ( B), to illustrate central granular caseation and epithelioid and multinucleated giant cells.

(84)

Pulmonary Tuberculosis (폐결핵)

Pulmonary Tuberculosis (폐결핵)

• 원발 폐결핵 (Primary pulmonary tuberculosis)

• 속발 또는 만성 폐결핵 (Secondary pulmonary

tuberculosis)

– 재활동 폐결핵 (Reactivation)재활동 폐결핵 (Reactivation) – 재감염 폐결핵 (Reinfection)

진행 폐결핵 (P

i

l

b

l

i )

• 진행 폐결핵 (Progressive pulmonary tuberculosis)

• 전신 또는 속립 폐결핵 (Miliary tuberculosis)

(85)

Natural history and spectrum of tuberculosis (TB)

(86)

Primary pulmonary tuberculosis

Definition

(원발폐결핵)

Definition : 결핵균 (Mycobacterium Tuberculosis)에 노출된 병력이 없는 환자에서 감염 ¾ 보통 기도를 통해 들어가므로 원발감염의 대부분은 폐에서 발생 – Localization

ƒ Ghon complex: initial focus of primary infection

= 흉막하 폐실질의 원발병터 (upper와 lower lobe 사이의 interlobar fissue의 직하방 또는 직상 방) + 폐문부 림프절의 건락림프절염 (caseous lymphadenitis)

¾ Course

ƒ Self-terminating course (95%)

• 대부분 asymptomatic 병변은 대부분 fibrosis와 calcification으로 바뀜대부분 asymptomatic, 병변은 대부분 fibrosis와 calcification으로 바뀜 ƒ Progressive primary tuberculosis

• 일부에서 특히 infant, children, 면역이 저하된 성인에서

• progressive spread with cavitation, tuberculous bronchopneumonia로 진행 ƒ Miliary tuberculosis (속립 결핵)

ƒ Miliary tuberculosis (속립 결핵)

(87)

• Primary pulmonary

tuberculosis Ghon

tuberculosis, Ghon

complex

The gray white parenchymal – The gray-white parenchymal

focus is under the pleura in the lower part of the upper lobe

( )

(topmost arrow).

– Hilar lymph nodes with caseationHilar lymph nodes with caseation are seen (lowermost arrows).

(88)

Secondary (reactivation) pulmonary tuberculosis

(속발 폐결핵)

(속발 폐결핵)

(1) 대부분 오래된 subclinical infection이 reactivation되어 생긴다 (1) 대부분 오래된 subclinical infection이 reactivation되어 생긴다

(primary tuberculosis의 5~10% 이하에서 발생) (2) primary보다 폐에 더 심한 손상을 준다

(2) primary보다 폐에 더 심한 손상을 준다.

(3) 흉부 방사선 사진에서 쇄골에 인접한 한쪽 혹은 양쪽 폐 상엽의 첨 부(apical) 혹은 후분절 (posterior segment)에서 시작하며 이 병소 부(apical) 혹은 후분절 (posterior segment)에서 시작하며 이 병소 를 Simon 병소라 명명한다.

(4) 직경 2 cm 이하의 작은 consolidation으로 시작된다 (4) 직경 2 cm 이하의 작은 consolidation으로 시작된다. (5) 대부분 인접 lymph node에도 Tbc activity가 있다.

(6) 처음 lung parenchyme에 작은 caseous necrosis가 생김

(89)

Progressive pulmonary tuberculosis

(진행 폐결핵)

(1) cavitary fibrocaseous tuberculosis (공동섬유

건락폐결핵)

(2) Tuberculous bronchopneumonia (결핵기관지

폐렴)

폐렴)

(3) Mili

t b

l

i (속립결핵)★

(3) Miliary tuberculosis (속립결핵)★

(90)

(1) Cavitary fibrocaseous tuberculosis

(

건락폐결핵)

1) erosion into bronchiole

(공동섬유건락폐결핵)

→ drainage of caseous focus → cavitation →↑O2 tension → growth and multiplication of the tubercle bacilli

2) cavity

i) in most, localized to apex (apical cavitary fibrocaseous tuberculosis) ii) lined by a yellow-gray caseous material

iii) wall off by fibrous tissue

iv) Thrombosed artery traverse the cavity → fibrous bridging band 3) dissemination of infective material )

i) through the airways → other sites of the lung or upper respiratory tract

ii) via lymphatics → lymph nodes → retrogressively other lymphatics → other areas of the lung or other organs

iii) through the blood

4) → advanced fibrocaseous tuberculosis

i) isolated minute tubercles, confluent caseous foci, 또는 large area of caseous necrosis 로 양쪽 lung의 하나 또는 모든 lobe에서 나타남

ii) 진행하면 pleural involvement

① serous pleural effusions ② frank tuberculous empyema

③ massive obliterative fibrous pleuritis

5) → endobronchial and endotracheal tuberculosis → irregular, ragged, necrotic, mucosal ulcer 생김

mucosal ulcer 생김

(91)

Cavitary Tuberculosis

Tuberculoma

(92)

(2) Tuberculous bronchopneumonia

(결핵기관지폐렴)

highly susceptible, sensitized individual에서

tuberculous 병변이 폐실질의 많은 부위에 빠

르게 퍼져서 diffuse bronchopneumonia 또는

lobar exudative consolidation을 형성하는 것.

tubercle이 잘 형성되지 않아 조직학적으로는

알기 어려우나, organism이 매우 많다.

(93)

(3) Miliary tuberculosis (속립결핵)

1) lymphohematogenous dissemination을 통해 폐에만 국

한되거나 다른 장기도 침범

( )

y

(속립결핵)

한되거나 다른 장기도 침범

2) lymphatics를 따라서 right heart를 거쳐서 폐로 들어가

2) lymphatics를 따라서 right heart를 거쳐서 폐로 들어가

alveolar capillay bed에 의하여 대부분 걸러지지만, 일

부 arterial systemic circulation으로 전신장기에 퍼짐

3) 호발부위는 liver, bone marrow, spleen, adrenal,

meninges, kidneys, fallopian tubes, and epididymis

g

,

y ,

p

,

p

y

4) 육안소견

다양한 크기(1 수 )의 l i – 다양한 크기(1~수㎜)의 lesion

– 육안으로 central caseation necrosis나 cavitation이 보이지 않는 distinct, yellow-white, firm consolidation

(94)

Miliary Tuberculosis

y

Miliary = like millet seeds

Å Miliary tuberculosis of the spleen. The cut surface shows numerous gray-white granulomas

.

(95)

Mycobacterium Avium-Intracellulare

Complex (MAC)

• Separate species, but the infections they cause are

so similar

Æ MAC

• Common in soil, water, dust, and domestic animals

• Clinically significant infection with MAC is uncommon

except among people with AIDS and low levels of

except among people with AIDS and low levels of

CD4+ lymphocytes (<60 cells/mm

3

)

– In AIDS patients

• Widely disseminated infections and abundant organism in many • Widely disseminated infections and abundant organism in many

organs (lung and GI tract)

• Morphology

• Morphology

– Widely dissemination – lymph node, liver and spleen

(96)

Viral Respiratory Infections

Viral Respiratory Infections

• 원인 바이러스

– 인플루엔자 A형과 B형 (Influenza viruses)

호흡기합포체 바이러스 (respiratory syncytial

– 호흡기합포체 바이러스 (respiratory syncytial

virus, RSV)

– Coxsackie virus

– ECHO virus

– Adenovirus

– Herpes virus

Herpes virus

(97)

바이러스 폐렴

바이러스 폐렴

• 임상증상

– 단순히 상기도 감염으로 감기처럼 경과

– 심한 감염증으로 진행하여 폐렴

– 발열, 두통, 근육통, 하지통

– 객담이 없는 마른기침이 특징적이다.

– 폐포벽에 부종과 삼출물로 심한 호흡곤란 유발

– 포도알균 또는 사슬알균에 의한 이차적 세균감염이

흔히 병발

(98)

Viral Respiratory Infections

Viral Respiratory Infections

5

이하는

h th

l

li

• 5μm이하는 reach the alveoli

Damage to bronchial epithelium

• Damage to bronchial epithelium

Æ Obstruct airway

Æ Superinfection (pneumococcus, staphylococcus, p (p , p y , Haemophillus)

• Histology of viral pneumonia; interstitial pneumonia

• Histology of viral pneumonia; interstitial pneumonia

– septal thickening & inflammatory infiltrate – focal necrosis of alveolar wall

– fibrin thrombi in capillaries

(99)

바이러스 폐렴

• 병리소견

육안검사

– 육안검사

• 폐는 적갈색으로 울혈 • 절단면은 붉은색의 거품이 포함된 액체가 소량 유출

– 광학현미경소견

사이질폐렴(i t titi l i )양상 • 사이질폐렴(interstitial pneumonia)양상 • 광범위폐포손상(diffuse alveolar damage)

* 핵내 봉입체가 관찰되는 viral pneumonia ★

– Measles (홍역), RSV (respiratory syncytial virus),

(

),

(

p

y y

y

),

Adenovirus, Herpes simplex, Varicella-zoster,

Cytomegalovirus

(100)

Primary atypical pneumonia

(원발비정형폐렴)

• Acute febrile respiratory disease (급성

발열성 호흡기질환)

발열성 호흡기질환)

with patchy inflammatory change in

• with patchy inflammatory change in

alveolar septa and pulmonary

i t

titi

interstitium ★

• "atypical"은 alveolar exudate 없는

interstitial pneumonitis를 의미

p

(101)

Primary Atypical Pneumonia

(원발비정형폐렴)

1. 원인균

Mycoplasma pneumoniae

(가장 흔함)

– Virus

• Influenza virus type A and B

• Respiratory syncytial virus (RSV) • Adenovirus • Rhinovirus • Rhinovirus • Rubeola • Varicella viruses

Chlamydia

(psittacosis, 앵무새병)

Coxiella burnetti

(Q fever)

(

)

(102)

Primary Atypical Pneumonia

(원발비정형폐렴)

2 형태

2. 형태

(1) affected area

red-blue, congested, subcrepitant

(2) Pleura

smooth, infrequent pleuritis or pleural effusion

(3) 폐의 alveolar wall과 pulmonary interstitium

에 국한하여 patchy inflammatory change

를 특징으로 한다.

(103)

(4) alveolar septa

– widened & edematous, mononuclear inflammatory infiltrates (lymphocytes, histiocytes, occasionally plasma cells)

(5) alveolar space내에 exudate가 없을 수도 있지만, 많은 환자에서 intraalveolar proteinaceous material, acellular exudate, hyaline membrane disease에서와 유사한 pink hyaline membrane이

membrane disease에서와 유사한 pink hyaline membrane이 alveolar wall을 lining하는 소견을 보인다.

→ reflect alveolar damage★

(6) superimposed bacterial infection

→ ulcerative bronchitis and bronchiolitis → anatomic change

(7) herpes simplex virus, varicella virus, adenovirus → necrosis of bronchial and alveolar epithelium

(104)

3. 임상경과

(1) major symptoms

fever headache muscle ache pain in the leg

fever, headache, muscle ache, pain in the leg,

NO cough

(2) edema and exudation

→ alveolocapillary block

alveolocapilla y block

→ evoke symptoms than scanty physical findings

(3) ↑cold agglutinin titer of serum in

(105)

Mycoplasma Pneumonia

Mycoplasma Pneumonia

• Mycoplasma pneumonia는 세포막이 없는 세균으로서 섬모 호흡 상피세포에 부착하여 증식한다. • 주로 건강한 청소년이나 청년에서 감염증을 잘 일으키고, 약 20% 에서는 증상이 없다. • 화농성 객담을 동반한 기침, 발열, 오한, 두통

• 혈청내 냉응집소(cold agglutinin titer)의 증가를 증명함으로써 진( gg ) 단할 수 있다.

• 흉부 방사선 소견상 폐결핵으로 오진되기 쉽고, 일반적인 급성 폐, 렴치료에 사용하는 항생제에는 거의 반응이 없으며 치료에 실패 할 가능성이 높다.

(106)

Cytiomegalovirus (CMV) pneumonia

1) immunocompromized patient

1) immunocompromized patient

2) predominantly mononuclear inflammatory infiltrate

2) predominantly mononuclear inflammatory infiltrate

3) viral inclusion bodies (in the nucleus and cytoplasm)

3) viral inclusion bodies (in the nucleus and cytoplasm)

(107)

* Herpes simplex pneumonia

1) interstitial process with mononuclear inflammation

2) alveolar cell hyperplasia, necrotizing bronchopneumonia 3) intranuclear viral inclusion (edge of the necrotic area)

* Adenovirus pneumonia

smudged nuclei, brick-like intranucler inclusion

* Influenza pneumonia

id f h l i h i l i wide range of morphologic change, no inclusion

* 핵내 봉입체가 관찰되는 viral pneumonia ★

핵내 봉입체가 관찰되는 viral pneumonia ★

Measles, RSV, Adenovirus, Herpes simplex, Varicella-zoster, CMV

(108)

Electron micrographs of adenovirus

Electron micrographs of adenovirus

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