Lung Path 3 - Interstitial through Diseases of Vascular Origin (Singh) Flashcards
1
Q
List some of the Interstitial lung diseases
A
UIP: ususal interstitial pneumonia
NSIP: non-specific interstitial pneumonia
COP: Cryptogenic Organizing Pneumonia
Sarcoidosis
Hypersensitivity Pneumonia
DSIP: Desquamative Interstitial Pneumonia
RB-ILD: Respiratory Bronchiolitis-Interstitial Lung Disease
- *LCH:** Langerhans Cell Histiocytosis
- *PAP:** PulmonaryAlveolarProteinosis
2
Q
What are the clinical sign/sx’s of chronic interstitial pulmonary diseases?
A
- Dyspnea and Tachypnea
- End-respiratory crackles “velcro-like”
- Restrictive patters on PFT (decreased DLCO, FVC)
- Basilar infiltrates on CXR
- Cyanosis (late)
- NO wheezing
3
Q
What is characteristically seen on CXR of someone w/ chronic interstitial pulmonary diseases?
A
- Bilateral lesions that take form of small nodules, irregular lines, or
- Ground-glass shadows
4
Q
Grossly, what is the end-stage lung seen in chronic interstitial pulmonary diseases referred to as?
A
Honeycomb lung
5
Q
Which 2 chronic interstitial lung diseases are categorized as granulomatous?
A
- Sarcoidosis
- Hypersensitivity pneumonitis
6
Q
What are some of the enviornmental and occupational factors which may be associated with Idiopathic Pulmonary Fibrosis?
A
- Cigarette smoking
- Expsoure to metal fumes and wood dust (industrial)
- Occupations such as: farming, hair-dressing, and stone-polishing
- GERD has also been implicated
7
Q
Loss-of-function mutations in which 2 genes has been implicated in Idiopathic Pulmonary Fibrosis?
A
- TERT
- TERC
*Encode components of telomerase
8
Q
What genetic factors have been assoicated with Idiopathyic Pulmonary Fibrosis?
A
Telomerase mutations
Surfactant mutations
MUC5B variant
9
Q
Some cases of Idiopathic Pulmonary Fibrosis are associated with a genetic variant leading to ↑ secretion of which mucin?
A
MUC5B
10
Q
Idiopathic pulmonary fibrosis is a disease most common in which age group?
A
>50 yo
11
Q
The histologic pattern of fibrosis seen in Idiopathic Pulmonary Fibrosis is referred to as what?
What is the imaging modality to diagnosed this condition based on its characteristic appearance?
A
- Cystic space surrounded by thick excessive fibrosis
- On CT
Usual interstitial pneumonia (UIP)
12
Q
Microscopically, what is the hallmark of Idiopathic Pulmonary Fibrosis; there is coexistence of what?
A
Patchy interstitial fibrosis*** (normal mixed with fibroblastic foci)
–> varies in intensity and age
Coexistence of early (fibroblastic foci) and late (collagenous) lesions
13
Q
In Idiopathic Pulmonary Fibrosis the formation of cystic spaces lined by hyperplastic type II pneumocytes or bronchiolar epithelium is known as what?
A
Honeycomb fibrosis
14
Q
The earliest lesions in Idiopathic Pulmonary Fibrosis contain exuberant what?
A
Fibroblastic proliferation (fibroblastic foci)
15
Q
Diagnosis of Idiopathic Pulmonary Fibrosis requires what?
A
Classic findings on high-resolution CT or pulmonary biopsy
16
Q
What are the initial sx’s of Idiopathic Pulmonary Fibrosis and the later sx’s with progression?
A
- Early —> ↑ dyspnea on exertion and dry cough
- Later –> hypoxemia, cyanosis and clubbing
17
Q
What is the prognosis and only definitive therapy for Idiopathic Pulmonary Fibrosis?
A
Median survival 3-5 years after Dx
Lung transplantation
Medication to arrest fibrosis inlcude Tyr kinase inhibitors and TGF-B inhibitors
18
Q
Why is it important to recognize pt’s with Nonspecific Interstitial Pneumonia?
A
Have much better prognosis than those w/ UIP
19
Q
What is the histomorphology of the cellular and fibrosing patterns of Nonspecific Interstitial Pneumonia?
A
Cellular = mild to moderate chronic interstitial inflammation; in UNIFORM parenchyma (can be patchy, but she emphaisized uniform)
Fibrosing = diffuse or patchy fibrotic lesions of roughly the SAME age
Resident cells include lyphocytes and eosinophils surrounding mild to moderate alveolar thickening
–> can be treated at this point.
20
Q
What is a major morphological difference between the lesions of Nonspecific Interstitial Pneumonia and Idiopathic Pulmonary Fibrosis?
A
In NSIP the lesions are at roughly SAME stage of development
21
Q
What 4 morphologial findings are absent in Nonspecific Interstitial Pneumonia?
A
- NO fibroblastic foci
- NO honeycombing
- NO hyaline membranes
- NO granulomas
22
Q
Which population is most likely to be affected by Nonspecific Interstitial Pneumonia?
A
Female NON-smokers in their 6th decade of life
23
Q
What are the key features of Nonspecific Interstitial Pneumonia seen on high-resolution CT?
A
Bilateral, SYMMETRIC, predominantly lower lobe reticular opacities
24
Q
How do patients with Cryprogenic Organizing Pneumonia (formerly BOOP) present and what is seen radiographically?
A
- Cough and dyspnea
- Patchy SUBpleural or
- peribronchial areas of airspace consolidation
25
What is the **hallmark** histology seen with Cryprogenic Organizing Pneumonia?
- **Polypoid plugs** of loose organizing CT (**Masson bodies**) within alveolar ducts, alveoli, and often bronchioles
- "**Balls** of **Fibroblasts**"
- superimposed on prior infection or fibrosis of chronic inflmmatory process
26
Prognosis and Tx of Cryprogenic Organizing Pneumonia?
- Some recover **spontaneously**
- Most need **oral steroids x 6 months** **+** for **complete recovery**
27
Cryprogenic Organizing Pneumonia is most often caused by what?
As a **response** to **infection** or **inflammatory injury** to the lungs
28
Which 3 autoimmune/CT disease can manifest as interstital lung disease?
- Rheumatoid arthritis
- Systmic sclerosis (scleroderma)
- SLE
Each of these can present as IPF, NSIP, or Organiznig pneumonia.
29
Inhalation of particles, pneumoconiosis, stimulate what inside the lung which lead to progression of disease?
**Resident INNATE** immune cells
30
Inhalation of coal dust may be a part of what 4 diseases?
- **Anthracosis**
- Coal **macules/nodules**
- **Progressive massive fibrosis --\> "Black lung"**
- **Caplan syndrome**
31
What occurs to the inhaled carbon pigment from coal, leading to Anthracosis?
Engulfed by alveolar or interstitial **macrophages**, which then accumulate in the CT along lymphatics in lungs or in hilus
32
Where are lesions (macules and nodules) of simple coal workers' pneumoconiosis most often seen in the lungs?
**Upper lobes** and **upper zones** of lower lobes
33
Indoor use of **smoky coal (bituminous)** for cooking and heating is associated with what complication?↑
↑ risk of **lung cancer**
34
What is the **most prevalent** occupational disease worldwide?
Silicosis
35
Which race has a higher risk for Silicosis?
Blacks
36
Which form of silica (crystalline/amorphous) is the most **fibrogenic**?
Crystalline (i.e., quartz, cristobalite, and tridymite)
37
What occurs after inhalation of silica particles; what is activated and what is released?
- Particles **phagocytosed** by **macrophages**
- **Activate** the **inflammasome**
- Leads to release of inflammtory mediators, **IL-1** and **IL-18**
38
Where in the lungs and in which LN's are the nodules of silicosis seen?
- **Hilar LN's**
- **Upper zones** of lungs
39
Histologically, what is the **hallmark** lesion seen with silicosis?
**Central** area of **WHORLED COLLAGEN** fibers w/ a **peripheral** zone of dust-laden **macrophages**
These dense collagenous nodules manifest as "eggshell calcification" of lymph nodes on radiography
40
Thin sheets of calcification may occur in the LN's of pt with silicosis and are seen radiographically as what?
**Eggshell calcification**
41
Silicosis is associated with an increased susceptibility to what infection; why?
**TB**; impaired ability of pulm. macrophages to kill phagocytosed mycobacteria
42
The onset of Silicosis may occur in what 3 ways (classification/duration)?
- **Slow and insidious** = 10-30 yrs after exposure
- **Accelerated** = within 10 yrs
- **Rapid** = week to months after intense exposure to fine dust high in silica
43
Pt's with Silicosis have double the risk for developing?
Lung cancer (as opposed to CWP)
44
Which asbestos fiber (serpentine or amphibole) is the **most** dangerous and pathogenic?
**Amphibole** = more aerodynamic, _smaller_ (easy to inhale to deeper pats of the lungs) and _less soluble_
45
Which property of asbestos fibers accounts for the remarkable synergy btw tobacco smoking and development of lung carcinoma in asbestos workers?
Toxic chemicals ca be **adsorbed** onto the fibers
46
Histologically, asbestosis is marked by diffuse pulmonary interstital fibrosis, indistinguishable from other causes, except for the presence of?
**Asbestos bodies** --\> **Golden-brown**, **fusiform** or **beaded rods** (covered in macrophage spit)
47
In asbestosis, inorganic particulates may become coated with **iron-protein** complexes and are called what?
**Ferruginous bodies**
48
Most common manifestation of asbestos exposure seen on the anterior and posterolateral aspects of the **parietal pleura** and over the dome of the diaphragm?
Known as?
-Well-circumscribed **pleural plaques** formation (dense collagen, often calcified)
**"Candlewax drippings**"
49
In contrast to other types of pneumoconiosis, where in the lungs does asbestosis typically begin?
**Lower lobes** and **subpleurally**
50
What type of neoplasm is assoicated with asbestosis?
**mesothelioma**
May occur decades after expsure
Lifetime exposure risk is 10%
51
Which cytotoxic drug used in cancer therapy may lead to pulmonary damage and fibrosis?
Bleomycin
52
What is the most common clinical pattern/organs of involvement seen with Sarcoidosis?
- **Bilateral HILAR lymphadenopathy** and **Lung** involvement
- **Eye** and **skin** lesions are 2nd in frequency
53
What is the CD4/CD8 T-cell like in pt's with Sarcoidosis?
- **CD4/CD8 T-cell ratios** range from **5:1** to **15:1**
- Suggests **pathogenic** involvement of **CD4+ helper T cells**
54
Which cytokine found in the bronchoalveolar fluid of pt with Sarcoidosis is a marker of disease activity?
TNF
55
Pt's with Sarcoidosis have abnormal immune responses including **anergy** to what?
Common **skin test** Ags such as *Candida* or tuberculosis PPD
56
Which 2 HLA genotypes are associated with Sarcoidosis?
- **HLA-A1**
- **HLA-B8**
57
What is the characterisic histological finding in the tissues of pt with Sarcoidosis?
**Non-caseating (Non-necrotizing) granulomas** composed of clustered **epitheloid macrophages**, often w/ **giant cells**
58
What are 2 characteristic morphological findings within giant cells of pt with Sarcoidosis?
inclusions known as **asteroid bodies**
**Schaumann bodies --\>** Laminated concentrations of Ca2+ and proteins
59
Why is there a high diagnostic yield of _bronchoscopic biopsies_ for Sarcoidosis?
Relatively **high frequency** of granulomas in the **bronchial submucosa**
60
Which LN's are most frequently affected by Sarcoidosis?
**Hilar** and **mediastinal**
61
Which 3 sites other than lungs and LN's are also commonly affected by Sarcoidosis and what is seen in each?
- **Spleen** - may be enlarged; granulomas often form **small nodules**
- **Liver** - may be enlarged; scattered granulomas often in **portal triad**
- **Bone marrow** - lesions w/ tendency for phalangal bones of hands and feet; small areas of bone resorption within marrow cavity w/ widening of the bony shafts
62
What 3 types of skin lesions may be encountered in Sarcoidosis?
**Subcutaneous nodules**
**Erythema nodosum**
Flat, slightly red and scaling, resembling those of **SLE**
63
Scattered granulomas associated with Sarcoidosis may be found in the liver, most often where?
**Portal triads**
64
What is the ocular involvement in some cases of Sarcoidosis?
- **Iritis** or **uveitis**, either **uni-** or **bilaterally**
- **Corneal opacities, glaucoma**, and **total vision loss** may occur
- Often accompanied by **inflammation** of the **lacrimal** glands w/ **suppression** of **lacrimation**
65
Bilateral sarcoidosis of the parotid, submaxillary, and sublingual glands constitutes a combined uveoparotid involvement designated as what?
**Mikulicz syndrome**
66
Muscle involvement in Sarcoidosis may be asymptomatic, but weakness, tenderness, aches, and fatigue should prompt consideration of what?
Occult Sarcoid Myositis
67
Majority of pt's with Sarcoidosis will present due to what signs/sx's?
- Insidious onset of **respiratory abnormalities** (i.e., dyspnea, SOB, cough, chest pain, hemoptysis)
- Constitutional sx's --\> **fever, fatigue, weight loss, night sweats**
--\> FEQUENTLY INCIDENTAL FINDING
68
Elevated serum levels of what enzyme and ion may be seen in Sarcoidosis?
- **↑↑↑ ACE**
- ↑ 1ᾳ-hydroxylase --\> **hyper**calcemia
69
What is the prognosis of Sarcoidosis; how does death most often occur?
- 60-70% **recover** w/ minimal or no residual manifestations
- 20% have permanent loss of lung function or vision
- 10-15% die of **cardiac** or **CNS damage**
70
Describe a "typical" sarcoidosis pt
\<40
Blacks are at an increased risk
Lung complains
ACE elevation
Alpha hydroxylase in liver also elevated --\> hyperCa2+
71
Staging of Sarcoidosis
72
Hypersensitivity pneumonitis primarily involves what structures in the lungs in constrast to asthma?
**Alveolar walls; granulomatous rxn** to inhaled Ags
_Airway-centered granulomata with assoicated lymphocytes_
Asthma = **conducting airways**
73
Why is history so important in the diagnosis of Hypersensitivity Pneumonitis?
- Disorders such as **Pigeon breeder's lung** (protein from bird feces)
**Farmer's lung** (spores in hey)
**Hot tub lung** - MAC
_Humidifier and air-conditioner lung are in this class as well_
--\> Pet birds and moldy basements are **easily missed** unless asked about specifically
74
Presence of noncaseating granulomas in 2/3's of pt's with hypersensitivity pneumonitis suggests what type of hypersensitivity rxn?
**T-cell** mediated (**type IV**)
75
Farmers lung is due to exposure to dusts generated from humid, warm, newly harvested hay that permits rapid proliferation of which spores?
**Thermophilic actinomycetes** (hey)
76
The histologic changes of hypersensitivity pneumonitis are characteristically centered around which lung structures?
Histologic changes are primiarly centered on **bronchioles**
1) Lymphocytes, plasma and macrophages in interstitium
(no eosiionophils)
2) noncaseating gramulomas in 2/3 of pts
3) interstitial fibrosis and obliterative bronchiolitis later
4) intra-alveolar infiltrate in 50% + of pts
77
What are 3 histomorphological changes seen with hypersensitivity pneumonitis?
1. **Interstitial** pneumonitis w/ **lymphocytes**, **plasma cells**, and **macrophages**
2. **Noncaseating granulomas**
3. **Interstital fibrosis** w/ **fibroblastic foci**, **honeycombing**, and **obliterative bronchiolitis** (late stages)
78
How soon after exposure to antigenic dust do sx's of hypersensitivity pneumonitis appear; last how long; what are the sign's/sx's?
- Appear **4-6 hours** after exposure; lasting **12 hours** to **days**
- Sx's = **recurring fever, dyspnea, cough,** and **leukocytosis**
79
What is seen on CXR of pt with hypersensitivity pneumonitis and what will PFT's show?
- **CXR** = micronodular interstitial infiltrates
- **Pulmonary Function Test** = acute **restrictive disorder pattern**
80
Why is it important to recognize the diseases of hypersensitivity pneumonitis as far as prognosis goes?
- If unresolved ---\> **chronic fibrotic lung disease**, respiratory failure w/ **dyspnea** and **cyanosis** and a ↓ TLC and compliance
- If exposure **removed** = sx's and disease **resolve**
81
What is the most striking morphological finding in Desquamative Interstitial Pneumonia?
Large # of **macrophages** w/ **abundant cytoplasm** containing **dusty brown pigment** (**smoker's macrophages**) in the airspaces
82
Some of the macrophages in desquamative interstitial pneumonia contain lamellar bodies which are what?
**Vacuoles** of **surfactant** from **necrotic type II pneumocytes**
83
What is the morphology of the alveolar septa in desquamative interstitial pneumonia and they are lined by what?
**Thickened** septa lined by **plump, cuboidal pneumocytes**
84
Desquamative interstitial pneumonia most often presents in which age group associated w/ what risk factor; what are the sign's/sx's?
- **Men** or **women** in the **4th** or **5th decade**; virtually all of whom **smoke**
- Insidious onset of **dyspnea** + **dry cough** over **weeks to months**, often with **clubbing** of digits = **restrictive lung disease** presentation
85
Patients with desquamative interstitial pneumonia often have an excellent response to what; what is the prognosis like?
- **Steroids** and **cessation of smoking**
- **Excellent prognosis**
86
Respiratory bronchiolitis-interstitial lung disease is part of a spectrum with desquamative interstitial pneumonia, except when does it present and what are the sx's like?
- **Earlier presentation** (3rd-4th decades)
**- Still smoking related**
- **Less symptomatic**; still has restrictive pattern w/ similar sx's
87
Hallmark of respiratory bronchiolitis-interstitial lung disease is presence of pigmented intraluminal macrophages where?
**First-** and **second-order respiratory bronchioles**
Fewer macrophages
Peribronchiolar metaplasia (fewer cilliated cells)
Fibrosis is only seen in advanced cases
88
Patchy submucosal and peribronchiolar infiltrate of lymphocytes and histiocytes in a smoker is characteristic of what disease?
Respiratory bronchiolitis-interstitial lung disease
89
Pulmonary Langerhans Cell Histiocytosis is most commonly seen in whom?
**Young smokers**; who improve after **smoking cessation**
90
Imaging of the chest in pt w/ Pulmonary Langerhans Cell Histiocytosis will show what?
**Cystic** and **nodular** abnormalities
91
Peripheral cysts of Pulmonary Langerhans Cell Histiocytosis may rupture and cause what?
Pneumothorax
92
What is a characteristic histiological finding in Langerhans Cell Histiocytosis (LCH)?
The langerhans cells of Pulmonary Langerhans Cell Histiocytosis will stain positive for what and negative for?
Stellate lung lesions \*
- **Positive** for **S100**, **CD1a** and **CD207** (**langerin**)
- **Negative** for **CD68**
93
In some cases of Pulmonary Langerhans Cell Histiocytosis, the Langerhans cells show neoplastic change due to activating mutation in what?
Serine/threonine kinase **BRAF**
94
Major histology and cell types of Pulmonary Langerhans Cell Histiocytosis?
- **Eosinophils**
- **Langerhans cells** (immature dendritic cells)
- Varying **fibrosis** and **cysts**
95
Pulmonary Alveolar Proteinosis (PAP) is a rare disorder related to which defects?
- Defects in **granulocyte-macrophage CSF** (**GM-CSF**)
or
- **Pulmonary macrophage dysfunction** = **accumulation** of **surfactant** in the **intra-alveolar** and **bronchiolar spaces**
96
Pulmonary Alveolar Proteinosis (PAP) is characterized by what radiologic findings?
**Bilateral** PATCHY **asymmetric** pulmonary **opacifications**
97
Autoimmune Pulmonary Alveolar Proteinosis (PAP) occurs primarily in whom and is due to antibodies against what?
- **Primarily** adults; represents **90%** of PAP cases
- Antibodies against **GM-CSF**
98
Loss of GM-CSF signaling seen in Pulmonary Alveolar Proteinosis (PAP) causes what?
Blocks terminal differentiation of alveolar macrophages **impairing** their ability to **catabolize surfactant**
99
Pulmonary Alveolar Proteinosis (PAP) can be treated how if autoimmune vs. secondary?
- **Autoimmune** = SQ injections of **GM-CSF**
- **Secondary** = Tx the underlying disorder
100
Secondary Pulmonary Alveolar Proteinosis (PAP) is uncommon and associated with what other disorders?
- Hematopoietic disorders (d/2 GM-CSF)
- Malignancies
- Immunodeficiency disorders
- Lysinuric protein intolerance (inborn error of metabolism)
- Acute silicosis
101
Hereditary Pulmonary Alveolar Proteinosis (PAP) is extremely rare and occurs in whom?
**Neonates**
may be autoimmune - most common
secondary, or
hereditary - very rare
102
Pulmonary Alveolar Proteinosis (PAP) is characterized by what morphological changes within the alveoli?
Homogenous, granular precipitate containing **surfactant** proteins that fill the avleoli and airspaces
Causing **focal-to-confluent consolidation** of large areas of the lungs w/ **minimal inflammation**
103
What is found in the alveolar precipitate of Pulmonary Alveolar Proteinosis (PAP) and what does it stain positive for?
- **Cholesterol clefts** and **surfactant proteins**
- Stains **(+)** for **PAS**
104
What is the standard of care and provides underlying benefit for pt's with Pulmonary Alveolar Proteinosis (PAP) regardless of cause?
**Whole-lung lavage**
105
How do adult pt's with Pulmonary Alveolar Proteinosis (PAP) present (signs/sx's)?
**Cough** + **andundant sputum** w/ chunks of **gelatinous material**
106
What is the most frequently mutated gene in surfactant disorders and via what inheritance pattern?
**Autosomal recessive** disorder assoc. w/ ***ABCA3***
107
Small lamellar bodies with electron dense cores are diagnostic for which mutation causing a surfactant dysfunction disorder?
***ABCA3* mutation**
108
Fractures of which bone cause a particularly high risk for PE?
Hip fractures
109
What are some primary and secondary hypercoagulable states that are risk factors for PE?
- **Primary** = factor V Leiden, prothrombin mutations, and antiphospholipid syndrome
- **Secondary** = obesity, recent surgery, cancer, OC use, and pregnancy
110
Which type of emboli are often seen in pt's who die after chest compressions performed during CPR?
Small **bone marrow** emboli
111
Indwelling central venous lines can act as a nidus for formation of what type of thrombi, with what complication?
**Right atrial thrombi**, which can **embolize** to **lungs**
112
PE have what 2 deleterious pathophysiologic consequences?
- **Respiratory compromise** due to the non-perfused, although ventilated, segment
- **Hemodynamic compromise** due to ↑ resistance to pulmonary blood flow caused by the embolic obstruction
113
In pt's w/ adequate CV function, which arterial supply sustains the lung parenchyma following PE; what is seen (hemorrhage/infarction)?
- **Bronchial** arterial supply
- **Hemorrhage** may occur WITHOUT **infarction**
114
Majority of infarcts associated w/ PE affect which lobes and occur as (single/multiple) lesions?
- **Lower lobes**
- **Multiple** lesions
115
How can a PE be distinguished from a postmortem clot?
Presence of the **lines of Zahn** in the thrombus
116
Infarction associated with PE is most often seen in whom?
Pt's w/ inadequate CV function
117
How does pulmonary infarction appear morphologically in the early stages and what is seen on the apposed pleural surface?
- **Hemorrhagic** as **raised**, **red-blue** area
- Pleural surface covered by **fibrinous exudate**
118
What occurs 48 hours after pulmonary infarct and what are the morphological changes as time progresses?
- Red cells begin to **lyse** --\> infarct becomes **paler** and eventually **red-brown** as **hemosiderin** is produced
- Over time, **fibrous replacement** begins at margins as a **gray-white peripheral zone** ---\> **contracted scar**
119
If a pulmonary infarct is caused by an infected embolus, there may be intense neutrophilic inflammatory rxn, and these lesions are knowna as what?
**Septic infarcts**
120
What is electromechanical dissociation in regards to the clinical presentation of a large pulmonary embolus?
**ECG has a rhythm**, but **no** **pulses are palpated** due to no blood entering pulmonary aterial circulation
121
If pt survives after a sizable pulmonary embolus the clinical syndrome may mimic what other condition, with what associated signs/sx's?
- May mimic **MI**
- Severe chest pain + dyspnea + shock
122
What are the associated signs/sx's of a pulmonary infarct?
- Dyspnea
- **Tachypnea**
- Fever
- Chest pain
- Cough + **hemoptysis**
123
Fibrinous pleuritis associated with pulmonary infarcts may produce what Physical Exam findings on the lung exam?
Pleural friction rub
124
How soon can pulmonary infarct be seen on CXR and what is seen?
- **12-36 hours**
- **Wedge-shaped** infiltrate
125
Via which imaging modality is the diagosis of PE usually made?
**Spiral CT angiography**
126
What are complications which may develop due to small pulmonary which are unresolved; greater risk for developing what?
- **Pulmonary HTN**
- Chronic **cor pulmonale**
- Pt's have 30% chance of suffering **2nd** embolus
127
Talc embolisms are common in whom?
IV drug users
128
Pulmonary HTN is defined as mean pulmonary artery pressure ≥\_\_\_\_\_\_mmHg at rest
**≥25 mmHg** at rest
129
What are the 5 classification of pulmonary HTN as classified by the WHO?
1. **Pulmonary arterial HTN** - primarily vascular disease
2. **2'** to **left-heart failure**
3. **2'** to **chronic pulmonary parenchymal** disease or **hypoxemia**
4. **2'** to **thromboembolic pulmonary HTN**
5. **Multifactorial**
130
List 5 common causes of pulmonary HTN
1. **Chronic obstructive** or **interstitial lung disease** (**group 3**)
2. **Congenital** or **acquired** heart disease (**group 2**)
3. **Recurrent thromboemboli** (**group 4**)
4. **Autoimmune disease** (**group 1**)
5. **Obstructive sleep apnea** (also **group 3**)
131
Idiopathic pulmonary HTN has what type of inheritance pattern?
**Autosomal Dominant** w/ **incomplete penetrance**
132
Inactivating germline mutations in which gene has been implicated in familial pulmonary HTN?
**BMPR2 gene**
133
Haploinsufficiency for BMPR2 leads to what pathologic changes causing pulmonary vascular thickening and occlusion?
**Proliferation** of **endothelial** cells AND **vascular smooth m.** cells
134
What are the hallmark morphological changes of pulmonary muscular and elastic arteries and right ventricle seen with all forms of pulmonary HTN (list 3)?
- **MEDIAL** **hypertrophy** of the **pulmonary** and **elastic arteries**
- **Pulmonary arterial ATHEROSCLEROSIS**
- **RV hypertrophy**
135
Which vessels are most prominently affected by pulmonary HTN and what's seen morphologically?
**Arterioles** and **small arteries** = **striking MEDIAL** hypertrophy and **INTIMAL** fibrosis
136
What type of lesions are **small**, vascular channels (**tufts of capillary**) that may be seen with **severe**, long standing pulmonary HTN?
**Plexiform** lesions
137
Idiopathic pulmonary HTN is most commonly seen in whom?
- **Women** who are **20-40 yo**
- Occasionally **young children**
138
What is the usual cause of death that ensues within 2-5 years of symptomatic idiopathic pulmonary HTN?
**Decompensated** cor pulmonale often w/ **superimposed thromboembolism** and **pneumonia**
139
In Goodpasture Syndrome autoantibodies destroy the glomerular BM in renal glomeruli and pulmonary alveoli giving rise to what disease in each system?
- **Rapidly progressive glomerulonephritis (RPGN)**
- **Necrotizing hemorrhagic interstitial pneumonitis**
140
Which sex and age group is most often affected by Goodpasture Syndrome?
**Males** in the **teens** or **20's**; majority are **active smokers**
141
Which 2 HLA subtypes are associated with Goopasture Syndrome?
**HLA-DRB1\*1501** and **\*1502**
142
What is the histology of the damage to alveolar walls in Goodpasture Syndrome?
**Focal necrosis** w/ **hemosiderin-laden macrophages**
143
What is the most common cause of death in pt with Goodpasture Syndrome?
Uremia
144
Most cases of Idiopathic Pulmonary Hemosiderosis occur in whom and how does it present?
- Most often **young children**; but some cases in **adults**
- Insidious onset of **productive cough, hemoptysis**, and **anemia** assoc. w/ diffuse pulmonary infiltrations
145
Tx for Idiopathic Pulmonary Hemosiderosis?
**Long-term** immunosuppression w/ **prednison** or **azathioprine**
146
What are the diagnostically important features of Polyangiitis w/ Granulomatosis (Wegener), especially in contrast to Sarcoidosis?
- **Capillaritis** and **scattered**, **POORLY** formed **granulomas**
- Granulomas of **sarcoidosis** are **rounded** and **well-defined**
147
Which biopsy technique may provide the only tissue necessary for diagnosis of Polyangiitis w/ Granulomatosis (Wegener)?
**Transbronchial** biopsy
148
What is Pneumoconiosis?
Occupational exposure to inhaled pollutants (dust or vapor)
**The smaller the particle, the worse the response is.**
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What is the cuase of Pneumoconiosis?
What makes it worse?
**Repeated** exposure to **high** level of pollutants
Exaggerated response is most likely d/2 a **genetic component**
**SMOKING** makes it worse d/2 impaired cilliary clearance
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What are the variants of coal workers' pneumoconiosis?
Anthracosis
Coal macules/nodules
Progressive massive fibrosis --\> worst outcome
Most Pt will have one of the milder forms, and will not have a progressive disease
