Lung Pathology

1
Lung Pathology

• Rodney Schmidt, MD, PhD
• (Carrie Chun, MD)
• schmidtr_at_u
• 598-6462

2
Lung Pathology

• Most is integrated with other lectures
• These lectures
• Reinforce certain points
• Different perspective
• Restrictive disorders (1st hour)
• Obstructive and others (2nd hour)
• 11/21 Clin-Path Correlation Conference
• HuBio546
• Cancers, pneumoconioses, other

3
Outline

• Reversibility of lung injury
• Faces of restrictive lung disease
• Acute
• Chronic
• Subacute
• Mechanisms
• Disease examples

4
Which injuries are reversible?
5
Irreversible Injuries

• Loss of basement membrane
• Emphysema
• Some pneumonias
• Mature fibrosis
• Pneumoconioses
• IPF
• Scars

Normal
Emphysema
6
Restrictive Lung Diseases

• Common features ? TLC ? Compliance

7
Restrictive Lung Diseases

• Differences
• Clinical context and pace
• Acute, chronic, (sub-acute)
• Etiology
• Mechanism of restriction

8
Acute Lung Injury

• Alveolar level injury
• Epithelial cells and/or endothelial cells
• Usually not cell-mediated
• Stereotyped injury and response
• Diffuse alveolar injury
• Hyaline membranes
• Organization
• Diffuse, severe, and rapidly progressive

9
ALI Clinical Contexts

• Adult Respiratory Distress Syndrome (ARDS)
• Rapid onset
• Respiratory insufficiency
• Arterial hypoxemia
• Refractory to oxygen therapy
• Causes (a sampling)
• Toxic gas inhalation
• Gram-negative sepsis
• Cytotoxic lung injury (drugs)
• Near-drowning
• Acute interstitial pneumonia (idiopathic)

10
How can a network of interconnected bubbles be
stable?
11
Disruption of surfactant layer

• Injury Type I (and Type II) pneumocytes
• Decreased surfactant production
• Plasma protein leak
• Inactivate surfactant (albumin and fibrin)

Hyaline membranes
12
Acute Injury
13
Acute Injury
Acute DAD
Normal
14
Organization and Repair
15
Late Fibrosis
16
(No Transcript)
17
Acute ILD

• Clinical ARDS
• Pathologic Diffuse alveolar damage
• Mechanism
• Surfactant deficiency (early)
• Fibrosis (late)
• Causes Multiple
• Prognosis Guarded (30 mortality)
• DDX Diffuse infections (esp. viral)

18
Chronic Restrictive Disorders
Kyphoscoliosis
Pulmonary Fibrosis
19
Chronic Interstitial Diseases

• Insidious onset
• Gradual progression over years
• Shared pathology Interstitial fibrosis
• Causes
• Inhaled dusts (pneumoconioses)
• Chronic granulomatous inflammation
• Auto-immune (collagen-vascular diseases)
• Idiopathic

20
Interstitial Lung Diseases
UIP
21
Granulomatous ILD

• Sarcoidosis
• Hypersensitivity pneumonitis
• Inhaled (extrinsic allergic alveolitis)
• Blood-borne (drug reactions)
• Chronic mycobacterial and fungal infections
• Wegeners granulomatosis

22
32yo woman with a rash

• c/o 1 week leg rash
• Also c/o slight dry cough, subjective fevers,
  joint pain
• PMH Healthy
• Meds None

23
(No Transcript)
24
Sarcoidosis

• Systemic granulomatous disease
• 90 involve pulmonary or thoracic lymph nodes
• Incidence not known
• Prevalence 10-20 per 100,000
• Unknown etiology and pathogenesis

25
Who gets Sarcoidosis?

• Typically presents between ages 20-35
• Women gt Men
• Ethnic differences
• 3-4x more common in American Blacks
• Rare in African Blacks, Asians, SE Asian Indians
• Geographical differences
• Temperate areas gt Tropical areas

26
Sarcoidosis-Presentation

• Pulmonary symptoms
• Dyspnea, non-productive cough, chest discomfort
• 50 of patients asymptomatic!
• Extrapulmonary symptoms
• Nonspecific constitutional symptoms
• Lofgrens Syndrome (erythema nodosum hilar
  nodes)
• Dependent on organ systems involved

27
(No Transcript)
28
(No Transcript)
29
(No Transcript)
30
Sarcoidosis-Diagnosis

• Characteristic clinical presentation
• Typical radiographic findings
• Non-caseating granulomas on biopsy
• Other etiologies ruled out

31
Sarcoidosis

• Non-necrotizing granulomas
• Uniform size
• Conglomeration

Lymphatic distribution
32
Hypersensitivity Pneumonitis

• Cellular interstitial pneumonitis lymphocytes
  in alveolar septa
• Small poorly formed granulomas
• Alveolar septal /- airway mucosal
• No necrosis
• Fibrosis if chronic

33
Infections granulomas

• Central necrosis
• Progressive enlargement

• Variable size
• Lymphatic distribution

34
Reasons to biopsy

• Identify granulomatous inflammation
• Differentiate sarcoid vs infection vs HSP
• Identify pathogenic dusts
• Assess pattern of inflammation and fibrosis
• UIP Idiopathic pulmonary fibrosis (IPF)
• Poor prognosis
• NSIP HSP, collagen-vascular, other
• Better prognosis
• Others (RB, GIP, OP, et al)

35
Usual Interstitial Pneumonia

• Chronic disorder (years)
• Insidious onset
• Progressive fibrosis
• Peripheral to central progression
• Unknown etiology
• Idiopathic pulmonary fibrosis

36
Usual Interstitial Pneumonia
37
Extensive fibrosis Peripheral predominance Pleural
cobble-stoning Parenchymal honey-combing
38
Usual Interstitial Pneumonia
39
Restrictive Diseases