Pathology - S2B1 - 3 Restrictive (Interstitial) Lung Diseases

Front 1

Define "Restrictive Lung Diseases"

Back 1

reduced total lung capacity in the presence of a normal or reduced expiratory flow rate

Front 2

Define Extrinsic Restrictive lung disease

Back 2

reduced expansion of lung parenchyma and decreased total lung capacity

Front 3

Define Intrinsic restrictive lung disease

Back 3

involves the space between the epithelial and endothelial basement membranes (interstitium)

Front 4

Give 4 examples of Extrinsic Restrictive Lung disease (chest wall disorders in the presence of normal lungs)

Back 4

1. Poliomyelitis
2. Severe Obesity
3. Pleural disease (mesothelioma)
4. Kyphoscoliosis = abnormal curvature of the spine in both a coronal and sagittal plane

Front 5

Give an example of an Acute Interstitial Lung disease

Back 5

ARDS

Front 6

2 synonym names for Usual Interstitial Pneumonia

Back 6

Idiopathic Pulmonary Fibrosis

Cryptogenic Fibrosing Alveolitis

Front 7

What is the most common type of Idiopathic Chronic interstitial pneumonia?

Back 7

Usual Interstitial Pneumonia

Front 8

Type of onset associated with Usual Interstitial Pneumonia

Back 8

Insidious (slow) = hard to diagnose

Front 9

Age range and mean age for Usual Interstitial Pneumonia

Back 9

40-70 years old

Mean = 55 years

Front 10

T or F: Usual Interstitial Pneumonia has no gender preference?

Back 10

True

Front 11

What have been demonstrated in the blood of patients with Usual Interstitial Pneumonia?

Back 11

ANA or Rheumatoid Factor

Front 12

Explain the pathogenesis of Usual Interstitial Pneumonia

Back 12

-Repeated cycles of Alveolitis triggered by an unknown agent
-Alveolitis -> Fibrosis -> distorted fibrotic lung with Cystic spaces (honeycomb lung)

Front 13

What immune response is associated with Usual Interstitial Pneumonia?

Back 13

Th2

Front 14

Abnormal activation of Wnt-beta catenin signaling pathway within mesenchymal cells of the fibroproliferative lesions is associated with this Diffuse Interstitial Lung Disease

Back 14

Usual Interstitial Pneumonia

Front 15

What is the prognosis for UIP?

Back 15

Chronic progressive downhill course

Average survival < 5 years

Front 16

What is the treatment for UIP?

Back 16

Steroids and Cyclophosphamide

Front 17

What is the mean survival time for UIP?

Back 17

3 years

Front 18

What are complications of UIP?

Back 18

Chronic lung disease

End stage lung (honeycomb lung)

Pulmonary Hypertension

Front 19

How is Non-specific interstitial pneumonitis (NSIP) distinguished from other lung diseases?

Back 19

uniform appearance (in all areas of biopsy) of interstitial inflammation, typically lymphocytes with rare plasma cells

Front 20

What is Non-specific Interstitial Pneumonitis treated with?

Back 20

Steroids

Front 21

T or F: UIP has a better prognosis than NSIP

Back 21

False: NSIP has a better prognosis

Front 22

What do NSIP patients present with?

Back 22

Dyspnea (shortness of breath)

Dry Cough

*both of several months duration

Front 23

Cryptogenic Organizing Pneumonia (COP) alternate names

Back 23

Bronchiolitis Obliterans Organizing Pneumonia (BOOP)

Allergic Alveolitis

Front 24

Define Cryptogenic Organizing Pneumonia

Back 24

- Allergic/inflammatory process involving BRONCHIOLES and ALVEOLAR spaces rather than large airways, as opposed to asthma

- Bronchioles eventually become totally fibrotic

Front 25

Describe the pathogenesis of Bronchiolitis Obliterans (COP)

Back 25

Type III hypersensitivity rxn and perhaps a component of Type IV
- Immune complex

Front 26

List 4 occupational hazards associated with Cryptogenic Organizing Pneumonia

Back 26

1. Farmer's lung
2. Sugar cane residue
3. Bird fancier's lung
4. Maple bark stripper's disease

Front 27

What is Farmer's lung due to exposure from?

Back 27

Thermophilic actinomycete spores in moldy hay
-Saccharopolysporia

Front 28

Distinctive type of patchy fibrosis composed of polypoid irregular plugs of fibrous tissue filling bronchioles, alveolar duct, and alveoli

Back 28

Cryptogenic Organizing Pneumonia (COP) (BOOP)

Front 29

Define Pneumonconioses

Back 29

NON-neoplastic reaction of the lung to inhaled mineral or organic dust

Front 30

In Pneumonconioses, the reaction in the lung will vary with these 5 things

Back 30

1. properties of the dust
2. size and shape of inspired particles
3. length of exposure
4. individual susceptibility
5. possible additional effects of other irritants

Front 31

What is the most important factor in Pneumonconioses?

Back 31

the capacity of the mineral or dust to stimulate inflammation and fibrosis

Front 32

What is Coal Worker's Pneumoconiosis caused by?

Back 32

inhalation of coal dust

Front 33

List the 3 stages of Coal Worker's Pneumonconioses

Back 33

1. Pulmonary Anthracosis
2. Simple CWP
3. Complicated CWP

Front 34

What characterizes CWP Pulmonary Anthracosis?

Back 34

-usually asymptomatic
-anthracotic pigment in interstistial tissue and hilar nodes
-alveolar macrophages with anthracotic pigment are called "dust cells"

Front 35

What characterizes Simple CWP?

Back 35

fibrotic opacities are smaller than 1 cm in upper lobes and upper portions of lower lobes
- little to no pulmonary dysfunction

Front 36

What characterizes Complicated CWP?

Back 36

- Fibrotic opacities larger than 2 cm with or without necrotic centers
- Black Lung disease
- Compromised lung function

Front 37

What can Complicated CWP lead to?

Back 37

1. Bronchiectasis = abnormally dilated bronchi filled with mucus and N0
2. Pulmonary HTN
3. Cor pulmonale = dilation and hypertrophy of the right side of the heart due to pulmonary HTN

Front 38

What is the most common occupational disease in the world?

Back 38

Silicosis

Front 39

What is Caplan's Syndrome?

Back 39

- Coexistence of Rheumatoid arthritis with a Pneumoconiosis (CWP)

- characterized by formation of large cavitating rheumatoid nodules in the lungs

Front 40

What is inhaled in Silicosis?

Back 40

Crystalline Silicon dioxide

Front 41

In what occupations is Silicosis most prevalent?

Back 41

Mine workers

Sandblasters

Glass workers

Front 42

Explain the Pathogenesis of Silicosis

Back 42

- quartz is highly fibrogenic and deposits in the UPPER lungs
- quartz activates and is cytolytic to alveolar MO
- MO release cytokines that stimulate fibrogenesis

Front 43

What is Silicosis associated with an increased susceptibility to?

Back 43

Tuberculosis

Front 44

In Asbestosis, where does diffuse pulmonary interstitial fibrosis start first?

Back 44

Lower lobes and subpleurally

Front 45

In what 2 locations in the world has asbestos been linked?

Back 45

Metsoya area in Greece

Turkey

*both related to mineral dust used in white stucco and wall paint

Front 46

Why are the most dangerous asbestos particles 1-5 microns in diameter?

Back 46

b/c they can reach the terminal small airways and air spaces and settle in their linings

Front 47

What is the most common feature of Asbestos exposure?

Back 47

Pleural plaques

*they do not contain asbestos bodies

Front 48

What are Ferruginous bodies?

Back 48

Asbestos fibers coated with Hemosiderrin and protein from MO

Front 49

What 2 cancers are associated with Asbestos and which one's risk is increased with smoking?

Back 49

1. Mesothelioma

2. Bronchogenic Carcinoma (Smoking)

Front 50

What does Malignant Mesothelioma arise from?

Back 50

Serosa of the pleura

Front 51

What is the most common Asbestos-related cancer?

Back 51

Bronchogenic Carcinoma

Front 52

What are the 2 geometric forms of Asbestos and which is most dangerous?

Back 52

1. Serpentine = curly, flexible
-more prevalent

2. Amphibole = straight, stiff
-most dangerous

Front 53

What special stain can be used to identify Asbestos?

Back 53

Prussian blue

Front 54

What are 6 Asbestos-related diseases?

Back 54

1. Pleural plaque
2. Pleural effusions
3. Pulmonary parenchymal interstitial fibrosis (asbestosis)
4. Bronchogenic carcinoma
5. Malignant mesothelioma
6. Laryngeal neoplasms

Front 55

Most common sites for Pleural plaques in Asbestosis

Back 55

1. anterior and posterolateral aspects of the Parietal Pleura

2. domes of the diaphragm

Front 56

In contrast to other inorganic dusts, asbestos can also act as what 2 things?

Back 56

1. tumor initiator

2. tumor promoter

*oncogenic effects are mediated by reactive free radicals

Front 57

List 5 groups of drugs associated with Interstitial Fibrosis

Back 57

1. Bleomycin and Bulsufan
2. Amiodarone
3. Cyclophosphamide
4. Methotrexate and Methysergide
5. Nitrosurea and Nitrofurantoin

Front 58

What is the definition of Sarcoidosis?

Back 58

disease of UNKNOWN etiology characterized by NON-CASEATING GRANULOMAS found in many organs and tissues

Front 59

What is the Clinical presentation of Sarcoidosis in 90% of all cases?

Back 59

-Bilateral hilar lymphadenopathy

-bilateral interstitial infiltrates

Front 60

Sarcoidosis has a 10-fold higher incidence in this group of people

Back 60

Black americans

*higher in females than males

Front 61

What can Sarcoidosis be mistaken for?

Back 61

Tuberculosis

Front 62

When diagnosing Sarcoidosis, why must you be absolutely sure?

Back 62

b/c treatment is Steroids and if the patient actually has TB, steroids will make it drastically worse

Front 63

What do you see histologically in Sarcoidosis?

Back 63

-Sarcoid non-caseating granuloma with epithelioid cells and MNGC's

Front 64

In Sarcoidosis, what are the non-caseating granulomas usually in close proximity to?

Back 64

Bronchioles

Front 65

What laboratory values are associated with Sarcoidosis? (4)

Back 65

1. increased Angiotensin-converting enzyme (ACE)

2. Hypercalcemia

3. Hypergammaglobulinemia

4. Increased ESR

Front 66

A 24-year-old African-American woman presents with fatigue unchanged by sleep, lack of energy, aches and pains, blurry vision, dry eyes and shortness of breath. A physical exam reveals small cutaneous bumps, uveitis and an enlarged liver by palpation. Other pertinent results were abnormal X-Rays, restrictive lung findings, increased serum angiotensin converting enzyme (ACE), and increased 24-hour calcium excretion. A bronchioloalveolar lavage revealed a CD4/CD8 ratio of >2.5 and a CD3/CD4 ratio of < 0.31.

Back 66

Sarcoidosis

Front 67

What is the prognosis for Sarcoidosis?

Back 67

-unpredictable clinical course

-overal, 65-70% of patients recover with minimal sequelae

Front 68

Dyspnea, uveitis, enlarged liver, skin lesions

Back 68

Sarcoidosis

Front 69

What is the most common symptom in Sarcoidosis?

Back 69

Dyspnea

Front 70

Describe the pathogenesis of Sarcoidosis

Back 70

1. disorder in immune regulation
2. CD4 Th cells interact with an unknown antigen
3. release of cytokines causing formation of noncaseating granulomas

Front 71

A 16-year-old bird owner presents with a history of 1 year of shortness of breath, particularly on exertion, productive cough, fatigue and weight loss. A physical examination revealed an increased respiratory rate, mild cyanosis, but notably there is no clubbing or fever. Chest X-Rays revealed reticular opacities in the upper lobes with reduced lung volumes and honeycombing. Bronchoalveolar labage revealed increased numbers of T lymphocytes, both CD4 and CD8.

Back 71

Hypersensitivity Pneumonitis

Front 72

Describe the pathogenesis of Hypersensitivity Pneumonitis

Back 72

1. exposure to antigen
2. patient develops IgG Ab's
3. 2nd exposure
4. Ab's combine with inhaled allergens to form immune complexes

Front 73

Explain 2 ways in which Desquamative Interstitial Pneumonia (DIP) is different from UIP

Back 73

1. patients are usually younger (42 vs. 55)

2. most patients respond to Steroid with means survival of 12 years compared to 5 for UIP

Front 74

What does a biopsy show in DIP?

Back 74

- instersitial inflammation

-striking accumulation of intra-alveolar Macrophages

Front 75

What is the final common pathway in all Restrictive Lung diseases?

Back 75

Honeycomb lung

Front 76

What are the hallmark histologic findings of Usual Interstitial Pneumonia?

Back 76

1. Chronic Interstitial INflammation

2. Interstitial Fibrosis

Front 77

Usual Interstitial Pneumonia

Back 77

What is this showing?

Front 78

A 60-year-old man presented with a 3-year history of cough and progressive dyspnea. His past medical history of was notable only for heavy smoking. He was not taking any drugs and his occupational and family history were unremarkable. One year prior to admission he noted the gradual appearance of dyspnea on exertion, which worsened with time and was associated with a dry cough, but no pain, fever or other systemic symptoms. On physical exam he had an elevated respiratory rate and bi-basilar “velcro” rales. No cyanosis, clubbing or organomegaly. 2 years later he presented with worsening symptoms and clubbing of his fingers.

Back 78

Usual Interstitial Pneumonia

Front 79

Usual Interstitial Pneumonia

Back 79

What lung disease?

Front 80

Usual Interstitial Pneumonia = Idiopathic Pulmonary Fibrosis

Back 80

What lung pathology?

Front 81

Non-specific Interstitial Pneumonitis

Back 81

This is distinguished from other causes by its uniform appearance of interstitial inflammation

Front 82

Bronchiolitis Obliterans = Cryptogenic Organizing Pneumonia

Back 82

What is this?

Front 83

Cryptogenic Organizing Pneumonia = Allergic Alveolitis
-fibrous plugs are seen

Back 83

What do these 2 slides show?

Front 84

Coal Worker's Pneumoconiosis

Back 84

What are these?

Front 85

Silicosis

Obstruction of airways and blood vessels

Back 85

What is this disease?

What can be a complication of these nodules?

Front 86

Asbestos

Back 86

What is this?

Front 87

Asbestos

Back 87

What is this?

Front 88

Pleural Plaques

Asbestos

Back 88

What are these called?

What is the cause?

Front 89

What type of occupation typically exposes one to Asbestos?

Back 89

Construction -> insulation

Front 90

What is this picture showing?

Back 90

Pleural Plaque caused by Asbestos

Front 91

Malignant Mesothelioma caused by Asbestos

Back 91

What is this picture showing?

Front 92

Mesothelioma caused by Asbestos

Back 92

What is this?

Front 93

Bleomycin

Bulsufan

Back 93

What 2 drugs could cause this fibrotic reaction in the lungs?

Front 94

Multisystem non-caseating granulomatous disease of unknown etiology
-Lung
-Liver
-Spleen
-Eyes
-Lymph nodes

Back 94

Sarcoidosis

Front 95

Sarcoidosis
-Bilateral Hilar Lymphadenopathy

Back 95

A 32 year old African-American woman presents with malaise, fever, and dyspnea. She also has a nodular rash on all extremities and has been suffering arthalgias in both knees.

Front 96

Sarcoidosis non-caseating Granulomas

Back 96

These lesion tend to be near Bronchioles

Front 97

A 25 year old black woman presents with Dyspnea, Hepatosplenomegaly, and erythema nodosum.
Lab values indicate increased ACE activity

Back 97

Sarcoidosis

Front 98

A 40 year old man presented with a cough that began 2 years ago and has progressively gotten worse. He also complains of dyspnea. Histology revealed a striking accumulation of Macrophages in the Alveoli. He was prescribed Steroids and his symptoms subsided.

Back 98

Desquamative Interstitial Pneumonia

Front 99

Desquamative Interstitial Pneumonia
-Intra-alveolar macrophages

Back 99

What is this Lung pathology?

Front 100

Pulmonary HTN

Cor Pulmonale = Right sided heart failure due to Lung pathology

Back 100

What is this?

What could it lead to?

Front 101

End-stage lung = Honeycomb lung
-dilated abnormal airways containing mucinous gray secretions

Back 101

What is this showing?

Front 102

Chronic condition characterized by the abnormal bilateral enlargement of glands in the head and neck, including those near the ears (parotids) and those around the eyes (lacrimal) and mouth (salivary) due to sarcoidosis
-Parotid, Submaxillary, Sublingual
-Lacrimal gland
-Salivary

Back 102

Mikulicz syndrome

Front 103

This is characterized by the INSIDIOUS development of FIBROTIC PULMONARY NODULES containing quartz crystals in the UPPER ZONES of the lungs

Back 103

Silicosis