Pathology 3 Flashcards
1
Q
REstrictive lung disease:
A
-expansion of lung is problem
2
Q
Things in lung that cause restriction:
A
- edema,
- cells in interstitium
- inflammation
- tumor
- granuloma
- fibrosis
3
Q
chronic diffuse interstitial disease defined:
A
- heterogeneous group of disorders characteried by inflammation and firosis of the pulm conncetive tissue
- principally the most peripheral and delicate interstitium in the alveolar walls
4
Q
Hallmark of chronic diffuse interstitial disease?
A
-REDUCED COMPLIANCE (stiff lungs) –> dyspnea –> hypoxia
5
Q
Interstitial lung diseases
A
1) capacity:
- dec total lung capacity
- FEV1 normal or dec proportionately
- FEV1:FVC ratio not reduced
2) presentation
- dyspnea
- hypoxia
- end-inspiratory crackles
- eventual cyanosis
3) x-rays
- diffuse bilateral infiltrative lesion by nodules, irregular lines, or ground glass shadows
4) clinical course
- may lead to pulm HTN or cor pulmonale == HONEY COMB LUNG AT ENDSTAGE
6
Q
Endstage interstitial lung disease:
A
-HONEY COMB(a lot of fibrosis)
7
Q
Types of interstitial lung disease:
A
1) acute:
- acute lung injury (ALI) or ARDS
2) Chronic
- environmental 25%
- sarcoidosis
- idiopathic pulm fibrosis
- collagen vascular
8
Q
Acute lung injury (aka non-cardiogenic pulmonary edema)
A
-abrupt onset of significant hypoxemia and pulmonary infiltrates in absence of cardiac failure
9
Q
Acute respiratory distress syndrome ARDS-
A
severe acute lung injury with greater hypoxemia
10
Q
Histologic manifestion of ALI and ARDS=
A
diffuse alveolar damage
11
Q
ARDS cuased by:
A
diffuse alveolar capillary damage (DAD)
= rapid onset of life-threatening respiratory insufficiency - refractory to oxygen therapy
-may lead to multi-system organ failure
-usually severe pulm edema = most common cause of non-cardiogenic pulm edema
12
Q
How does damage to capillary and alveolar membranes in ALI and ARDS happen?
A
1) direct injury from outside
- infectious agent (pneumonia)**
- aspiration**
- oxygen tox
2) indirect injury -systemic from inside
- shock (trauma, burns, surgery..)**
- sepsis**
- inhaled toxins
- transfusion related (TRALI)
13
Q
Three main causes of ARDS/ALI?
A
sepsis
infection
shock
14
Q
ALI/ARDS characteristics:
A
-bilateral pulmonary infiltrates on chest x-ray
-PaO2(arterial)/Fi(environmental)O2 normally 375-400
in ALI ratio < 300
in ARDS raio <200
15
Q
ARDS pathogenesis:
A
- uncontrolled activation of acute inflammatory system
- imbalance between proinflam and antiinflam mediation
- sequestration and activation of neutrophils
- diffuse damage to alveolar capillary walls
- inc vascular permeability and alveolar thickening
- loss of diffusion capacity
- widespread surfactant abnormalities bc of Pneumocte 1 and 2 damage
16
Q
ARDS pathway in neonates:
A
occurs with deficiency in pulmonary surfactant
17
Q
Symptoms of ARDS:
A
1) first dispnea and tachypnea
2) cyanosis and hypoxemia
18
Q
What helps ARDS patients?
A
inhalation of nitric oxide - decreases PA pressure and arterial resistance
-ventilation perfusion mismathc-hypoxemia
19
Q
Mortality of ALI/ARDS?
A
40%!! pretty high!
20
Q
ARDS
A
1) morphology:
- lung heavy, firm red and stiff
2) micro:
- congestion
- interstitial and alveolar edema
- fibrin deposition
* -alveolar hyaline membranes**
- proliferation of T2pneuomocytes
- phagocytosis of membranes
3) organization: of exudate can follow= interstitial fibrosis —> honey comb lung down he line
21
Q
three phases of ARD
A
1) acute exudative (0-7 day)
2) proliferative phase (1-3 weeks)
3) fibrotic/healing phase (3-4 weeks)
22
Q
What is TRALI
A
- trasfusion related ALI
- within 6 hours of transfusion
- due to anti HLA or anti HNA antibodies
- no pre-existing acute lung injury before transfusion
23
Q
Major categories or interstital lung disease:
A
1) fibrosiing
2) granulomatous
3) eosinophilic
4) smoking related
24
Q
Diffuse interstitial disease
A
MORE LONG TERM
- initially alveolitis in interstitium of alveoli (accumulation of inflammatory and immune effector cells within alveolar walls and spaces)
- heterogenous stimuli
- Leukocytes accumulate in the alveoli=distort normal alveolar structures; release damaging mediators; parenchyma injurred and fibrosis stimulated; MACROPHAGE PLAYS CENTRAL ROLE IN FIBROSIS
- final stage= end stage fibrotic lung (HONEYCOMB LUNG)***
25
honeycomb lung think:
- cor pulmonale
- R sided HF
- pulm htn
26
Idiopathic pulmonary fibrosis (IPF)
- unkn etiology
- characterized by diffuse interstitial fibrosis
- also called cryptogenic fibrosing alveolitis
- histology="usual interstitial pneumonia (UIP)" but NOT specific for IPF
27
Idiopathic pulmonary fibrosis (IPF) - clinical course:
- 2/3s of patients >60 yrs and M>F
- insidious onset of SOB (6 mo)
- nonproductive dry cough and inc dyspnea
- advanced cases=hypoxemia, cyanosis, clubbing
- severe pulmonary HTN, cor pulmonale, death
- mean survival 3 year
- only definitive tx = lung transplant
28
How to diagnose IPF=
diagnosis of exclusion
29
IPF IMPORTANT TO FIND?
ONLY ONE THAT DOES NOT RESPOND TO STEROIDS!!! ALL THE OTHERS DO
30
IPF - pathogenesis:
- IPF caused by repeated cycles of epihelial activation/injury by some unidentified agent = chronic inflammation--> fibrosis
- -> something regarding telomerase shortening and apoptosis leading to epithelial activation and injury
- inflammation and induction of TH2 T-cells with eosin, mast cells, IL4, IL5, IL13 in lesion
- abn wound healing = fibroblastic foci (crazy fibro prolif)
31
Early microscopic findings of IPF:
Overtime...
-Late?
- alveolitis
- fibroblastic foci
- overtime get early and late lesions at the same time ** (temporal heterogeneity)
- dense fibrosis --> collapse of alveolar walls, formation of cystic spaces lined by hyperplastic type II pneumocytes (HONEYCOMB LUNG!)
32
Hallmark of UIP=
patchy interstital fibrosis varying in intensity and age
33
UIP (IPF) TX?
-NEED TRANSPLANT
34
```
DIP
COP (BOOP)
NSIP
PAP
HSP
```
TX?
-RESPONDS TO STEROIDS
35
Causes of honeycomb lung:
- IPF
- interstitial pneumonia
- diffuse alveolar damage DAD
- inorganic dust exposure
- interstital granulomatous diseases
- eosinophilic granuloma
- GE Reflux/aspiration
36
Rheumatoid arthritis pulmonary involvement:
- chronic pleuritis
- difuse interstitial pneumonitis and fibrosis
- intrapulmonary rheum nodues
- pulm htn
37
Scleroderma pulmonary involvement:
- NSIP is classic
- diffuse interstitial fibrosis-main cause of death
UNIFORM AND DENSE FIBROSIS
38
SLE pulmonary involvement:
- pathy, transient, parenchymal infiltrates
| - occasionally severe pneumonitis
39
Pneumoconioses defined:
-non-neoplastic lung reaction to inhalation of any aerosol, includin mineral dusts, organic and inorganic particles, fumes, or vapors (AIR POLLUTION!)
Most common:
- coal dust
- silica
- asbestos
40
small particles and pneumoconioses:
-smaller and so can get into pulm fluids and reach toxic levels = ALI
41
Larger particles and pneumoconioses:
-resist dissolution and persist = fibrosis
42
physiochemical reactivity and pneumoconioses
- direct tissue damage by release of free rads and other chemical groups
- OR triggers macros
43
Most dangerous size and why w/ pneumoconioses?
- 1-5micrometers
- reach terminal small airways and alveoli
- lodge in bifurcation of distal airways
44
Key factor of pneumoconioses:
-How much of this stuff is inhaled and how likely is this inhaled dust to stimulate fibrosis
45
Wide spectrum of pneumoconiosis in Coal miners:
1) asymptomatic anthracosis - no cellular reaction, msot innocuous
2) simple coat workers pneumoconiosis (CWP) - macule, nodule with collagen fibrils; minimal lung dysfunction
3) complicated CWP-progressive massive fibrosis
- compromised lung function
NO RISK FOR LUNG CANCER OR TB
46
What is progressive massive fibrosis (PMF)
- severe confluent, fibrosing reaction which may complicate any pneumoconiosis
- scarring in areas of dust accumulation
47
Simple CWP morphology:
- 1-2mm coal macules;nodules
- located primary adjacent to respiratory bronchioles
- can lead to dilation of adjacent alveoli (centrilobular emphysema)
48
Complicated CWP (PmF) morphology
- large, black scars, multiple, bilateral and peripheral
- appearance similar to rheumatoid nodule
- progressive leads to PMF, pulm htn ,cor pulmonale
49
Caplan syndrome:
- coexistence of rheumatoid arthritis with a pneumoconiosis
| - development of distinctive nodular pulmonary lesions
50
Silicosis- pathogenesis:
- breath it in - quartz (most dangerous crystalline)
- quartz phagocytosed by macrophages ==> release of IL1 *TNF*, free radicals, fibrogenic cytokines
- macrophage dies and releases silica particle = amplified process
- fibroblast proliferation occurs = collagen deposition = leads to PMF
INC SUSCEPTIBILITY TO TB AND SILICA IS CARCINOGENIC!!!!
51
Silicosis morphology:
- concentrically arranged collagenous nodules, begin as small lesions in upper lungs = large more diffuse with disease progression
- nodules coalesce into larger collagenous scar == leads to PMF
- may be calcified (eggshell)
-MICRO= hyalinized WHORLS of collagen, scant inflammation
52
serpentines vs amphiboles (asbestos components)
- serpentines more solubleand easier to get rid of - flexible and curled
- amphiboles = more of the problems with this guy - brittle and straight
53
Amphibole exposure correlates with:
-MEsothelioma!
54
Asbestos bodies are
asbestos in lungs lined by iron
- stain with prussia nblue
- DUMBBELL
55
ASbestos morphology
- begins as fibrosis around respi bronchioles --> involved alveolar sacs and alveoli
- -> HONEYCOMB LUNG
- typically LOWER lobes and subpleurals pace
56
Consequences of asbestosis:
- 5x inc risk for lung cancer
- if smoking too = 55x inc in risk of lung cancer
-1000x increase in mesotheliomas-- takes 20-40years to develop
57
Clinical course of asbestosis:
- dyspnea on exertion and later at rest
- cough with sputum productin
- can lead to CHF< cor pulmonale, honeycomb and death
58
Asbestos on the lungs;;;;
pleural plaque
- lung cancer
- scaring
- mesothelioma..
59
Bleomycin pulmonary disease complication:
-pneumonitis and fibrosis
60
Methotrexate pulmonary disease complication:
-hypersensitivity pneumonitis
61
Amiodarone pulmonary disease complication:
pneumonitis and fibrosis
62
nitrofurantoin pulmonary disease complication:
-hypersensitivity pneumonitis
63
aspirin pulmonary disease complication:
bronchospasm
64
beta antagonists pulmonary disease complication:
bronchospasm
65
complication of radiation therapy
| -radiation induced lung disease
- acute - 1-6 months and therapy = fever, dyspnea, pleural effusion, infiltrates
- GIVE STEROIDS
-chronic - failure to resolve --> fibrosis - diffuse alveolar damage ; severe atypia
66
Sarcoidosis defined:
systeic disease of unkn cause
-noncaseating granulomas in many tissues and organs
-DIAGNOSIS OF EXCLUSION
67
sarcoidosis clinical:
- variable presentation depending on organs involved and disease activity
- most frequent targets=lung or hilar LN, skin, eye
- inc prevalence in non-smokers
- african american females
68
sarcoidosis - clinical presentation:
- sometimes completely asympt
- often = insidious onset pulmonary symptoms, fever, NS, WL
- if acute onset=fever, erythema nodosum, polyarthritis, inc IgG calcium, ACE
69
sarcoidosis diagnosis:
-DIAGNOSIS OF EXCLUSION
70
sarcoidosis - etiology:
-disordered immune reg in genetically predisposed people exposed to certain environmental antigens
71
sarcoidosis - immunologic factors (etiology)
- interstitial and intra alveolar accumulation of CD4 Th1
- inc levels of TH1 cytokines (IL2 & IFN gamma) = more t-cells and macro activation
- inc cytokines (IL8 and TNF) = brings more T-cels and monocytes
CELLULAR MEDIATED (DAMAGE)=FORMS GRANULOMAS!!
72
Sarcoidosis HLAs
HLA-A1 and HLA-B8
| -familial!!
73
Sarcoisosis tissue shows:
-CLASSIC WELL-FORMED NONCASEATING GRANULOMAS (CD4 TH1 cells surround)
- some obstruction due to granulomas
- eventual diffuse interstitial fibrosis --> honey comb lung
-patterns develop along lymphatics!
74
Most frequently involved organ - sarcoidosis?
lungs durps
75
Sarcoidosis of eyes and salivary glads called:
mikulicz syndrome
76
potato nodes seen in
sarcoid
77
sarcoid - oddities in the granulomas:
- schaumann bodies: little lamellated calcified structure, usually in giant cells (also common in berylliosis)
- asteroid bodies: star shaped eosinophilic bodies made of compressed intermediate filaments; also commonly in foreign body giant cells
78
sarcoidosis - progression and outcome
-not bad - 70% treated well
10-15% die
79
hypersensitivity pneumonitis
- occupational disease resulting from inc susceptibility to inhaled antigens such as moldy hay
- immune mediated (TYPE 3-deposition of antibody-antigen complex and 4-cell mediated delayed type), predominantly interstitial disorder caused by intense often prolonged exposure to inhaled organic dusts or antigens
- RESTRICTIVE DISEASE PRESENTATION
- INVOLVES PRIMARILY ALVEOLI (allergic alveolitis)
80
Hypersensitivity pneumonitis - inhalation of what:
```
-organic dusts with antigens made up of:
spores of thermophilic bac
true fungi
animal proteins
bacterial products
```
81
Hypersensitivity pneumonitis - presentation:
1) acute: large exposure to antigen =
- severe dyspnea
- cough,
- high fever and chills 4-6 hrs
- resolves in several days
2) chronic: prolonged exposure to small amounts ofa ntigen=
- insidious onset of dyspnea
- cough
- fatigue
- resp failure due to chronic interstitial disease
82
Hypersensitivity pneumonitis - hypersensitivtiy type 3 and 4 when?
3- is EARLY
| 4- is LATER (granulomatous)
83
Hypersensitivity pneumonitis - -types/most common:
**-farmers lung: spores of thermophilic actinomyces in hay
- pigeon breeders lung - proteins from bird feathers, serum, or poop
- humidifier or air-conditioner lung: thermophilic bacteria
84
Hypersensitivity pneumonitis - morphology
1) acute = neutrophils in interstitium
| 2) chronic=mononuclear interstitial infiltrate (lymphs, plasma cells, and macrophages)
85
silo fillers disease (NO/NO2) - what happens:
-breathe the gas = pulmonary edema in minutes --> develop into widespread bronchiolitis obliterans with scar tissue
86
smoking-related interstitial diseases:
-desquamative interstitial pneumonia (DIP)
87
-desquamative interstitial pneumonia (DIP)
- SMOKING RELATED INTERSTITIAL DISEASE
- more males than females
- insidious onset of dyspnea and dry cough
- no desquamation
- numerous intra-alveolar macrophages (smokers macrophages) = HARD TO BREATHE
- with emphysema usually
- proliferation of T2 pneumocytes
RESPONDS AWESOME TO STEROIDS 100% survival
88
pulmonary alveolar proteinosis (PAP)
- bilateral patchy pulmonary opacification on X-ray
- homogeneous, granular precipitate within alveoli
- focal to confluent consolidation of large areas of lung
- ACCUMULATION OF ACELLULAR SURFACTANT - in intraal veolar and bronchiolar spaces (PAS+)
- MINIMAL inflammatory response- normal alveolar walls
DOES NOT CAUSE FIBROSIS AND INTERSTITIAL THICKENING!!! *!**!**!*!*!*!*!*
89
Pulmonary alveolar proteinosis - clinical shit:
- insidious onset cough
- Chunks of white gelatinous-appearing sputum jello
- fever
-some recover others not
- NO progression to fibrosis
- whole lung lavage therapy
