Pathology 3 Flashcards Preview

Respiratory 1 > Pathology 3 > Flashcards

Flashcards in Pathology 3 Deck (89):
1

REstrictive lung disease:

-expansion of lung is problem

2

Things in lung that cause restriction:

-edema,
-cells in interstitium
-inflammation
-tumor
-granuloma
-fibrosis

3

chronic diffuse interstitial disease defined:

-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

Hallmark of chronic diffuse interstitial disease?

-REDUCED COMPLIANCE (stiff lungs) --> dyspnea --> hypoxia

5

Interstitial lung diseases

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

Endstage interstitial lung disease:

-HONEY COMB(a lot of fibrosis)

7

Types of interstitial lung disease:

1) acute:
-acute lung injury (ALI) or ARDS
2) Chronic
-environmental 25%
-sarcoidosis
-idiopathic pulm fibrosis
-collagen vascular

8

Acute lung injury (aka non-cardiogenic pulmonary edema)

-abrupt onset of significant hypoxemia and pulmonary infiltrates in absence of cardiac failure

9

Acute respiratory distress syndrome ARDS-

severe acute lung injury with greater hypoxemia

10

Histologic manifestion of ALI and ARDS=

diffuse alveolar damage

11

ARDS cuased by:

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

How does damage to capillary and alveolar membranes in ALI and ARDS happen?

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

Three main causes of ARDS/ALI?

sepsis
infection
shock

14

ALI/ARDS characteristics:

-bilateral pulmonary infiltrates on chest x-ray
-PaO2(arterial)/Fi(environmental)O2 normally 375-400
in ALI ratio < 300
in ARDS raio <200

15

ARDS pathogenesis:

-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

ARDS pathway in neonates:

occurs with deficiency in pulmonary surfactant

17

Symptoms of ARDS:

1) first dispnea and tachypnea
2) cyanosis and hypoxemia

18

What helps ARDS patients?

inhalation of nitric oxide - decreases PA pressure and arterial resistance
-ventilation perfusion mismathc-hypoxemia

19

Mortality of ALI/ARDS?

40%!! pretty high!

20

ARDS

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

three phases of ARD

1) acute exudative (0-7 day)
2) proliferative phase (1-3 weeks)
3) fibrotic/healing phase (3-4 weeks)

22

What is TRALI

-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

Major categories or interstital lung disease:

1) fibrosiing
2) granulomatous
3) eosinophilic
4) smoking related

24

Diffuse interstitial disease

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