Pathology (Lungs)

Front 1

which bronchus is more likely to have aspiration?

Back 1

right bronchus

it is more vertical with the trachea than is the left bronchus

Front 2

what is an acinus?

Back 2

terminal respiratory unit, composed of respiratory bronchioles, alveolar ducts, and alveolar sacs

about 7mm in diameter

distal to terminal bronchiole

Front 3

components of the alveolar septum from blood to air

Back 3

endothelial cells with basement membrane

thin portions: basement membranes of endothelium and epithelium are fused

thicker portions: basement membranes are separated by interstitial space with a few elastic fibers, collagen, fibroblasts, mast cells, and rare lymphocytes

Front 4

type I pneumocytes

Back 4

very flat

cover 95% of surface

more vulnerable to injury

Front 5

type II pneumocytes

Back 5

rounder

produce, contain, and secrete surfactant

can proliferate and repair and give rise to type I pneumocytes

Front 6

what perforates alveolar walls? why is this clinically important?

Back 6

pores of Kohn

permit passage of bacteria and exudate between adjacent alveoli

Front 7

agenesis of lungs

Back 7

can involve 1 lobe, 1 lung, or both lungs

if unilateral, other lung can enlarge

often causes other abnormalities, especially with the right lung (cardiac anomalies)

Front 8

what are the causes of lung hypoplasia?

Back 8

anything that causes oligohydramnios (e.g. Potter's sequence)

diaphragmatic hernia

**abnormalities that compress the lung**

Front 9

congenital lung cysts

Back 9

single/multiple abnormal detachment of a fragment of primitive foregut, ranging in size from microscopic to 5cm, usually located adjacent to bronchi or bronchioles

most are bronchogenic cysts

consists of bronchial epithelium (pseudostratified columnar epithelium) filled with mucus or air

Front 10

what are the complications of congenital lung cysts?

Back 10

infection
rupture into bronchi (causing hemorrhage and/or hemoptysis)
rupture into pleural cavity (causing pneumothorax and/or interstitial emphysema)

Front 11

bronchopulmonary sequestration

Back 11

congenital mass of lung tissue without normal connection of airway

blood supply arises from aorta or branches (not pulmonary circulation)

extralobar vs. intralobar

Front 12

extralobar bronchopulmonary sequestration

Back 12

congenital mass of lung tissue without the normal connection to an airway located external to the lung (anywhere in the thorax or mediastinum)

blood supply arises from aorta or branches (not pulmonary circulation)

found as abnormal mass lesions in infants

look for other congenital anomalies

Front 13

intralobar bronchopulmonary sequestration

Back 13

congenital mass of lung tissue without the normal connection to an airway located within the lung

blood supply arises from aorta or branches (not pulmonary circulation)

causes infection and bronchiectasis

found in older children in association with recurrent infections or bronchiectasis

Front 14

atelectasis

Back 14

incomplete expansion of a neonatal lung or collapse of a previously inflated lung

if substantial, can reduce oxygenation and predispose to infection

Front 15

resorption (obstruction) atelectasis

Back 15

collapse of a previously inflated lung caused by complete obstruction of an airway; causes resorption of residual oxygen

blood flow remains normal, but lung volume diminishes

mediastinum may shift towards the obstructed lung if a substantial portion of lung is involved

usual cause is excess secretions or exudate in small bronchi

Front 16

what are the causes of resorption (obstruction) atelectasis?

Back 16

excess secretions or exudate in small bronchi

- asthma, bronchitis, bronchiectasis
- foreign body aspiration
- post-operative obstruction b/c pt doesnt want to cough up obstructive material (less frequent b/c of inc. use of laprascopic surgery)
- tumors are an unusual cause (they usually do not completely obstruct the bronchus

Front 17

compression atelectasis

Back 17

pleural cavity is either partially or completely filled with a substance (usually fluid) which compresses the lung

causes: pus accumulation; CHF; tumors causing effusions; stab/penetration wounds; elevation of diaphragm

mediastinum shifts away from the involved lung

Front 18

what are the causes of compression atelectasis?

Back 18

pus accumulation

congestive heart failure (most common)

neoplasms causing effusions (fluid is more bloody than that seen in CHF)

stab wounds or other external penetration (if it nics an intercostal artery)

elevation of the diaphragm (diaphragmatic hernia)

Front 19

what is the most common cause of compression atelectasis?

Back 19

congestive heart failure (CHF)

Front 20

contraction atelectasis

Back 20

localized or general fibrosis (restrictive lung diseases) in the lung prevents full lung expansion

only type of atelectasis that is irreversible

Front 21

how is an atelectasis reversible?

Back 21

except for contraction atelectasis, they (resorption and compression) can be reversed by removal of the obstructive or compressive agent

Front 22

what is the complication for atelectasis?

Back 22

infections

Front 23

what are the two basic mechanisms that cause pulmonary edema?

Back 23

1) hemodynamic abnormalities - increased hydrostatic pressure, e.g. left sided CHF

2) increased capillary permeability b/c of microvascular injury - endothelial/epithelial injury

Front 24

pulmonary edema caused by hemodynamic abnormalities

Back 24

most common cause: increased hydrostatic pressure (i.e. caused by lt-sided CHF

gross: wet, heavy lungs, especially in the basal parts of the lower lobe

clinical: impaired respiratory function and predisposition to infection

Front 25

microscopic morphology of pulmonary edema caused by hemodynamic abnormalities

Back 25

pink, frothy fluid in alveolar spaces

congested capillaries

hemosiderin-laden macrophages (heart-failure cells)

with chronic disease, see fibrosis and thickening of alveolar wall/septa

hemosiderin + fibrosis = brown induration over time

Front 26

what are heart failure cells?

Back 26

hemosiderin-laden macrophages in the lungs caused by ingestion of iron from trapped red blood cells

Front 27

pulmonary edema caused by increased capillary permeability

Back 27

microvascular injury to endothelial or alveolar epithelial cells leads to edema

protein and fluid are leaked into the interstitium and subsequently into alveoli

contributes to ARDS when diffuse

Front 28

acute lung injury

Back 28

noncardiogenic pulmonary edema

abrupt onset of hypoxemia and diffuse infiltrates in absence of cardiac failure

characterized by rapid onset of severe resp. infufficiency, cyanosis, severe refractory hypoxemia; may progress to extrapulmonary multisystem organ failure

if severe, called ARDS; if no underlying cause, called acute interstitial pneumonia

mortality is about 40%

Front 29

causes for acute lung injury/ARDS/acute interstitial pneumonia

Back 29

direct lung injury
diffuse infections
oxygen toxicity
inhalation of toxins or other irritants
aspiration of gastric contents

systemic causes:
septic shock, traumatic shock, severe pancreatitis, burns, complicated cardiac surgeries, hemodialysis, or narcotic OD

Front 30

pathogenesis of acute lung injury/ARDS/acute interstitial pneumonia

Back 30

diffuse, bilateral damage to alveolar capillary walls that usually starts in endothelium, or occasionally by direct injury to pneumocytes, and then the other is soon involved

inc. permeability allows for edema and fibrin exudate, which contributes to hyaline membrane

endothelial damage triggers formation of microthrombi in capillaries

inc. pro-inflammatory mediators especially NF-kappaB and dec. anti-inflammatory mediators; within 30 minutes, synthesis of IL8 in macrophages is increased which stimulates neutrophil activation and chemotaxis

Front 31

why are neutrophils important for the pathogenesis of ARDS?

Back 31

increased activation and sequestration in lungs

release of tissue-damaging products

maintain inflammatory cascade

Front 32

gross morphology of ARDS

Back 32

heavy, firm, red, boggy, edematous

Front 33

microscopic morphology of ARDS

Back 33

early - congestion & edema, with inflammation and fibrin deposition; formation of hyaline membrane composed of fibrin, necrotic cell remnants, and edema fluid

late - type II pneumocyte hyperplasia (attempt to regenerate alveolar lining); granulation tissue in walls and alveolar spaces; usually resolves w/ min functional impairment

Front 34

what are the complications of unresolved ARDS?

Back 34

1) intra-alveolar fibrosis
2) thickened alveolar septa (poor gas exchange)
3) proliferation of interstital cells and collagen deposition

Front 35

what are hyaline membranes composed of?

Back 35

fibrin
necrotic cell remnants
edema fluid

Front 36

clinical features of acute lung injury/ARDS?

Back 36

pts are usually already seriously sick from the initiating problem

present with profound dyspnea and tachypnea, increasing cyanosis and hypoxia

xray is initially normal, but eventually diffuse bilateral infiltrates form

lungs become focally stiff with decrease in functional volume, causing a ventilation-perfusion mismatch with hypoxemia

if fatal, usually b/c of sepsis or multi-organ failure

Front 37

acute interstitial pneumonia

Back 37

usually occurs after 50 years old

clinically similar to ARDS, but no etiology is known; often starts with URI-like symptoms and progresses to ARDS-like symptoms in less than 3 weeks

1/3-3/4 die, most within 1-2 months; survivors get recurrence or develop chronic interstitial disease

Front 38

obstructive pulmonary diseases

Back 38

increase in resistance to airflow, owing to partial or complete obstruction at any level (trachea to resp. bronchioles)

PFTs with limitation of max airflow rates during forced expiration

**FEV1 is decreased**

(1) emphysema
(2) bronchitis
(3) asthma
(4) bronchiectasis

Front 39

restrictive pulmonary diseases

Back 39

reduced expansion of lung parenchyma, with decreased total lung capacity

PFTs with reduced total lung capacity and normal/proportionately reduced expiratory flow rate

**FEV1 is normal/reduced proportionately to lung capacity**

(1) chest wall disorders
(2) chronic interstitial diseases
(3) chronic infiltrative diseases

Front 40

what is the major symptom of COPD?

Back 40

dyspnea (difficulty breathing)

Front 41

emphysema

Back 41

abnormal, permanent enlargement of airspaces distal to the terminal bronchiole, accompanied by wall destruction without obvious fibrosis

strong association with heavy smoking

4 types:
(1) centriacinar (centrilobular)
(2) panacinar (panlobular)
(3) paraseptal (distal acinar)
(4) irregular emphysema
**(3) and (4) are minor forms**

Front 42

centriacinar (centrilobular) emphysema

Back 42

95% of emphysema

central (proximal) parts of acini, formed by resp. bronchioles are enlarged, but distal alveoli spared; if severe, distal acinus is secondarily involved

normal and abnormal airspaces found in some acini

walls of the affected spaces often have anthracotic pigmentation; bronchi and bronchioles are commonly surrounded by inflammation

more common and more severe in the upper lobes, especially the apices

pts are usually heavy smokers and often have concurrent chronic bronchitis

Front 43

what is the fourth leading cause of morbidity and mortality in the US?

Back 43

emphysema

Front 44

panacinar (panlobular) emphysema

Back 44

acini uniformly enlarged from respiratory bronchiole to the alveoli (very large air spaces)

involves entire acinus, but not necessarily the entire lung

affects lower zones and anterior margins; most severe at bases

associated with alpha1-antitrypsin deficiency

pt must stop smoking

Front 45

paraseptal (distal acinar) emphysema

Back 45

proximal portion of acinus is normal, but the distal part is enlarged; multiple enlarged air spaces from 0.5 to 2 cm in diameter

adjacent to pleura, along the connective tissue septa, and at the margins of lobules; adjacent to areas of fibrosis or scarring

more severe in upper half of lungs

responsible for most spontaneous pneumothorax in young adults (sudden severe SOB in pts in 20s-30s)

Front 46

irregular emphysema

Back 46

acinus irregularly involved (no set pattern of enlargement)

associated with scarring

usually asymptomatic

Front 47

protease-antiprotease mechanism of emphysema pathogenesis

Back 47

disturbance in balance of proteases (elastase) with antiprotease (alpha-1-antitrypsin) is helped by oxidant-antioxidant imbalance to cause alveolar wall damage

pts with homozygous alpha-1-antitrypsin deficiency develop emphysema, compounded by smoking

Front 48

what is the function of alpha-1-antitrypsin?

Back 48

it is the major inhibitor of proteases, especially elastase

Front 49

what is the normal phenotype for alpha-1-antitrypsin? what is the most common deficiency phenotype?

Back 49

normal: PiMM (90% of the population)

deficiency: PiZZ (80% develop emphysema)

Front 50

what is the hypothesis to explain the aggravation of protease-antiprotease imbalance caused by smoking?

Back 50

a) particles attract neutrophils and macrophages to alveoli
b) stimulate the release of elastase from neutrophils as well as enhancing elastase activity in macrophages
c) oxygen free radicals contained in cigarette smoke inhibit alpha-1-antitrypsin and deplete antioxidants in the lung

Front 51

what types of elastase are inhibited by alpha-1-antitrypsin?

Back 51

neutrophil elastase is inhibited

macrophage elastase is not inhibited

Front 52

why do smokers get centriacinar emphysema rather than other types?

Back 52

smoke makes it to the small bronchi and bronchioles, attracting neutrophils and macrophages to these areas

Front 53

why do patients with alpha-1-antitrypsin develop panacinar emphysema?

Back 53

the enzyme is lacking throughout the acinus, which causes damage throughout

Front 54

what is the effect of loss of elastic fibers in the walls of alveoli surrounding respiratory bronchioles in emphysema patients?

Back 54

bronchiole collapse during expiration resulting in functional airflow obstruction (therefore an obstructive disease)

Front 55

gross morphology of emphysema

Back 55

upper 2/3 of lungs are more affected in centriacinar emphysema (most common form)

in panacinar emphysema, lungs are enlarged when inflated and can overlap/hide the heart

in irregular emphysema, see large apical blebs or bullae secondary to scarring

Front 56

microscopic morphology of emphysema

Back 56

with destruction of walls, get abnormally large alveoli causing grossly apparent blebs and bullae

club-shaped septa protrude into alveolar spaces

respiratory bronchioles and vessels may be compressed

may have fibrosis but not much inflammation

may have bronchitis/bronchiolitis

Front 57

clinical features of emphysema

Back 57

sits forward in hunched over position and pt is barrel chested with obvious prolonged expiration (expiratory phase > inspiratory phase)

pts not symptomatic until they lose 1/3 of functional lung capacity

dyspnea becomes progressive with cough, wheezing (confused for asthma), severe weight loss (confused for CA)

pink puffers - remain well oxygenated (pink) by overventilating (puffers)

Front 58

pink puffers vs. blue bloaters

Back 58

pink puffers - pt overventilates and so they remain well oxygenated - primary pathology is emphysema

blue bloaters - pt is hypercapneic, hypoxemic, and cyanotic - primary pathology is chronic bronchitis

Front 59

what are the causes of death in COPD?

Back 59

1) respiratory acidosis and coma
2) right sided heart failure
3) lung collapse from pneumothorax

Front 60

compensatory emphysema

Back 60

hyperinflation of the lung with no destruction of septal walls/alveoli

removal of a lung or a portion of a lung causes hyperexpansion of the residual parenchyma to compensate

Front 61

senile emphysema

Back 61

larger ducts with smaller alveoli

Front 62

obstructive overinflation emphysema

Back 62

lungs are expanded b/c air is trapped in by subtotal obstruction via a tumor or foreign body
a) ball-valving = air can get in but not out like a one-way valve
b) complete obstruction of bronchus = air enters via pores of Kohn (collaterals bringing air in behind the obstruction)

Front 63

bullous emphysema

Back 63

see large subpleural blebs or bullae

accentuation of one of the basic forms of emphysema creating subpleural cavities > 1cm

can rupture, causing pneumothorax

Front 64

interstitial emphysema

Back 64

entrance of air into the lung stroma, mediastinal connective tissue or subcutaneous tissue, rather than alveolar spaces

in most cases, alveolar tears in combination with cough and obstruction provide avenue for air to enter the stroma

penetration wounds or fractured ribs can "cut" the lungs and allow air entry

Front 65

chronic bronchitis

Back 65

clinical disease, not pathological, defined as a persistent cough with sputum production lasting for at least 3 months in at least two consecutive years

can be associated with emphysema (pts often have both)

leads to cor pulmonale and heart failure; causes squamous metaplasia and dysplasia, leading to cancer

mild/simple - no evidence of airflow obstruction
chronic asthmatic bronchitis - intermittent bronchospasm and wheezing
obstructive - some associated emphysema, especially in heavy smokers

Front 66

pathogenesis of chronic bronchitis

Back 66

1) chronic irritation caused by inhaled substances/particles
2) neutrophils are attracted and secrete proteases
3) hypersecretion of mucus and hypertrophy of submucosal glands of trachea & bronchi
4) sputum overproduction causes productive cough

infections have a secondary role, maintaining the bronchitis once it starts or producing exacerbations

smoking is a paramount influence (90% occurs in smokers)

Front 67

gross morphology of chronic bronchitis

Back 67

hyperemic, boggy, swollen mucosa

excess mucus or mucopurulent secretions and pus that can form casts (pull off bronchi and retain the shape)

Front 68

microscopic morphology of chronic bronchitis

Back 68

increased mucus, chronic inflammation (with mostly lymphocytes)

increase in size of mucus secreting glands in trachea and bronchi (reid index is increased)

increased # of goblet cells in small airways; may have squamous cell metaplasia or even dysplasia

mucus plugging, inflammation, fibrosis in small airways causes bronchiolar narrowing

in severe disease, see obliteration of lumens of bronchioles due to fibrosis (bronchiolitis obliterans)

Front 69

bronchiolitis obliterans

Back 69

obliteration of lumens of bronchioles due to fibrosis, seen in severe chronic bronchitis

Front 70

clinical features of chronic bronchitis

Back 70

chronic productive cough, infections, cor pulmonale with heart failure

may develop emphysema

blue bloaters - hypoxemia, mild cyanosis, hypercapnea

Front 71

bronchial asthma

Back 71

chronic, relapsing, inflammatory disorder, characterized by hyperreactive airways leading to episodic reversible bronchoconstriction, owing to increased responsiveness of tracheobronchial tree to stimuli

Sx: severe dyspnea, coughing, wheezing, chest tightness; especially seen at night and early AM

Front 72

status asthmaticus

Back 72

acute exacerbation of asthma that does not respond to standard treatments of bronchodilators and steroids

Sx: chest tightness, rapidly progressive dyspnea (shortness of breath), dry cough, use of accessory muscles, labored breathing and extreme wheezing

life-threatening episode of airway obstruction considered a medical emergency

complications: cardiac and/or respiratory arrest

Front 73

atopic asthma

Back 73

most common type of bronchial asthma

classic type I HSN triggered by exposure to extrinsic allergen, which increases generation of IgE

usually begins in childhood, commonly with a family history

wheal and flare reaction is seen on skin test with the offending allergen

inhaled antigen stimulates induction of type 2 helper T cells that release IL-4 and IL-5, which promote IgE production by B cells, growth of mast cells, and activation of eosinophils - subsequent exposure results in class I reaction

Front 74

what is the purpose of RAST tests?

Back 74

look for IgE against a panel of allergens

**used for atopic asthma**

Front 75

non-atopic asthma

Back 75

bronchial asthma initiated by non-immune mechanisms, commonly a viral respiratory tract infection (inhaled irritants may contribute)

probably caused by hyperirritability of the bronchial tree b/c inflammation caused by the infection lowers the threshold of vagal (bronchoconstricting) receptors to irritants

Front 76

drug induced asthma

Back 76

uncommon bronchial asthma and hives caused by aspirin ingestion, triggered even by tiny doses

pt has recurrent rhinitis and nasal polyps

aspirin inhibits COX pathway of arachidonic acid metabolism w/o affecting LOX, resulting in bronchoconstricting leukotriene release

Front 77

occupational asthma

Back 77

bronchial asthma that develops after repeated exposure to fumes, dusts, gases, or chemicals; attacks can be triggered by minute quantities

combination of type I reaction, release of bronchoconstrictors, and hypersensitivity response

Front 78

pathogenesis of atopic asthma

Back 78

inheritance of susceptibility genes making person prone to develop strong TH2 response to allergens

TH2 cells secrete interleukins that promote allergic inflammation and stimulate B cells to produce Abs, esp. IgE; the interleukins also recruit eosinophils and stimulate mucus production

Front 79

acute phase of atopic asthma

Back 79

bronchoconstriction predominates within minutes of reexposure to allergens, which cause sensitized mast cells on mucosal surfaces

released mediators open intercellular tight junctions so that the antigen can get to the more numerous submucosal mast cells

stimulation of subepithelial vagal receptors provokes bronchoconstriction, edema, and mucus secretion

cytokines from mast cells attract other inflammatory cells, which cause the late phase response

Front 80

late phase of atopic asthma

Back 80

inflammation predominates starting 4-8 hours after an initial attack and lasting 12-24 hours or longer

epithelial cells produce eotaxin, which recruits and activates eosinophils

eosinophils release major basic protein which causes epithelial damage and airway constriction

Front 81

what mediators of atopic asthma respond to drug intervention?

Back 81

LTC4, D4, E4
- all cause bronchoconstriction, increased vascular permeability, and increased mucus secretion

ACh
- causes smooth muscle constriction

Front 82

what mediators in atopic asthma are affected little/not at all with drug intervention?

Back 82

histamine - causes bronchoconstriction

PgD2 - causes bronchoconstriction and vasodilation

PAF - releases histamine and serotonin from platelets

IL-1, IL-6, TNF, NO

Front 83

genetics of asthma

Back 83

gene cluster on 5q - codes IL-3, 4, 5, 9, 13 and IL4R - involved in IgE regulation, as well as mast cell and eosinophil growth/differentiation

polymorphism of CD14 gene coding monocyte receptor for endotoxin

ADAM-33 polymorphisms may accelerate proliferation of bronchial smooth muscle and fibroblasts leading to bronchial hyperplasia and fibrosis

beta2 adrenergic receptor variations associated with differential airway hyperresponsiveness

acidic mammalian chitinase upregulation (YKL-40) correlates with severity of asthma

Front 84

polymorphisms in IL13 gene have strong, consistent association with what?

Back 84

allergies and asthma

Front 85

gross morphology of bronchial asthma

Back 85

overdistended lungs caused by overinflation

occlusion of bronchi and bronchioles by thick mucous plugs

Front 86

microscopic morphology of bronchial asthma

Back 86

- mucous plugs with whorls of shed epithelium (Curschmann spiral)
- eosinophils and Charcot-Leyden crystals of an eosinophil membrane protein
- thickened basement membrane and sub-membrane fibrosis
- edema & inflammation of bronchial wall (eosinophils constitute 5-50%)
- increased size of submucosal glands in glandular layer
- bronchial muscle wall hypertrophy

Front 87

clinical features of bronchial asthma

Back 87

an attack can last for hours and can be followed by prolonged cough as the pt starts bringing up the secretions

if severe, can eventually lead to emphysema, bronchiectasis, cor pulmonale, and heart failure

superimposed infections can lead to chronic bronchitis, bronchiectasis, and pneumonia

Front 88

what is a Curschmann spiral?

Back 88

mucous plugs with whorls of shed epithelium seen in bronchial asthma

Front 89

what are Charcot-Leyden crystals?

Back 89

crystals of an eosinophil membrane protein that are formed after its excretion

seen in patients with bronchial asthma

Front 90

bronchiectasis

Back 90

permanent dilation of bronchi and bronchioles caused by destruction of muscle and elastic tissue, resulting from or associated with chronic necrotizing infections

with better antibiotic control of infections, is now uncommon

Front 91

causes of bronchiectasis

Back 91

1) bronchial obstruction (disease is localized to the obstructed segment with tumor or foreign body; diffuse disease with asthma or chronic bronchitis)
2) congenital/hereditary (defect in bronchial development, sequestration, cystic fibrosis, immunodeficiencies, or Kartagener syndrome)
3) necrotizing pneumonias (S. aureus, H. influenzae, P. aeruginosa, TB, viruses, Aspergillus)

Front 92

what is the most common cause of bronchiectasis?

Back 92

cystic fibrosis

Front 93

what is Kartagener syndrome?

Back 93

aka primary ciliary dyskinesia

rare, ciliopathic, autosomal recessive genetic disorder that causes a defect in the action of the cilia lining the respiratory tract (lower and upper, sinuses, Eustachian tube, middle ear) and fallopian tube, and also of the flagella of sperm in males

main consequence of impaired ciliary function is reduced or absent mucus clearance from the lungs, and susceptibility to chronic recurrent respiratory infections, including sinusitis, bronchitis, pneumonia, and otitis media

causes bronchiectasis with progressive damage to the resp. system

Front 94

general pathogenesis of bronchiectasis

Back 94

combination of obstruction and infection

obstruction interferes with normal clearing mechanisms and causes accumulation of secretions; if obstruction persists, especially in periods of growth, causes abnormal development of lungs

infection causes inflammation, necrosis, fibrosis, and dilation of airways

Front 95

pathogenesis of bronchiectasis caused by cystic fibrosis

Back 95

defective mucociliary action and accumulation of thick secretions cause obstruction which predisposes to infection

repeated infections damage walls, muscle, and elastic fibers

small bronchioles become obliterated by fibrosis

Front 96

primary ciliary dyskinesia

Back 96

AR disorder with variable penetrance that causes the absence or shortening of dynein arms that are responsible for coordinated beating of cilia so that the cilia beat in many directions rather than just one direction

poorly functioning cilia leads to retention of secretions which then leads to recurrent infections

males are infertile due to the ineffective mobility of sperm tails

called Kartagener syndrome if the pt has bronchiectasis, sinusitis, and situs inversus
- present in half of pts with primary ciliary dyskinesia

Front 97

pathogenesis of bronchiectasis caused by allergic bronchopulmonary aspergillosis

Back 97

pt has hypersensitivity to aspergillus

complication of asthma/cystic fibrosis

severe inflammation with lots of eosinophils

mucus plugs cause the obstruction which interferes with normal clearing mechanisms and leads to the accumulation of secretions

Front 98

gross morphology of bronchiectasis

Back 98

usually bilateral lower lobe involvement that is more severe in distal bronchi/bronchioles

if caused by a local process, there is sharp, segmental lung involvement

dilated airways (up to 4x normal)
- cylindroid = long, tube-like
- fusiform
- saccular

airways can follow the airway out to the pleural surface (normally they stop 2-3cm from the pleura)

cut surface - cysts filled with mucoid or mucopurulent material

Front 99

microscopic morphology of bronchiectasis

Back 99

acute/chronic inflammation within the wall

desquamation of lining epithelium and ulceration of the alveolar wall

pseudostratification of columnar epithelium, or squamous metaplasia of remaining epithelium

can have abscess formation along with bronchiectasis

with time, see fibrosis of bronchial/bronchiolar wall

Front 100

clinical features of bronchiectasis

Back 100

(1) severe and persistent cough
- tends to be paroxysmal, especially on rising in the AM
- postural change (sitting up) causes drainage of pus into the bronchi
(2) copious amounts of foul-smelling purulent sputum
(3) fever if infection is present
(4) mixed organisms are cultured

Front 101

general facts about diffuse (restrictive) interstitial diseases

Back 101

heterogeneous group, characterized by diffuse chronic lung involvement of pulmonary connective tissue, especially interstitium of alveolar walls

cause dyspnea, tachypnea, and eventual cyanosis, but no wheezing

Xray shows diffuse infiltration by small nodules, irregular lines, or ground glass shadows

eventually causes secondary pulmonary hypertension and right-sided heart failure

in advanced disease, see honeycomb lung; it is hard to tell the cause at this point

Front 102

idiopathic pulmonary fibrosis

Back 102

aka cryptogenic fibrosing alveolitis
aka chronic interstitial pneumonitis
aka usual interstitial pneumonitis

restrictive pulmonary disease

Front 103

pathogenesis of idiopathic pulmonary fibrosis

Back 103

repeated cycles of epithelial activation/injury by an unidentified agent

inflammation is thought to be mainly TH2 mediated (eosinophils, mast cells, IL-3, IL-4)

TGF-beta1 is released from injured epithelial cells and generally promotes fibrosis

abnormal epithelial repair causes excess fibroblast/myofibroblast proliferation, leading to more fibrosis

Front 104

familial pulmonary fibrosis

Back 104

mutations that shorten telomeres cause rapid senescence and increased apoptosis of alveolar epithelial cells

TGF-beta1 negatively regulates telomerase activity, which facilitates apoptosis and the death/repair cycle

TGF-beta1 also regulates caveolin-1, which is an inhibitor of fibrosis

Front 105

gross morphology of idiopathic pulmonary fibrosis

Back 105

cobblestoned pleural surfaces from scar retraction

cut-surface: firm rubbery white areas from fibrosis
- lower lobe predominates
- subpleural and along interlobular septa

Front 106

microscopic morphology of idiopathic pulmonary fibrosis

Back 106

patchy interstitial fibrosis; cystic spaces are lined by hyperplastic type II pneumocytes or bronchial epithelium (honeycomb fibrosis)

early - exuberant fibroblastic proliferation
later - fewer cells with more collagen deposition

very typical is coexistence of early and late lesions (this isn't seen in other fibrotic diseases)

mild to moderate inflammation in fibrotic areas

Front 107

clinical features of idiopathic pulmonary fibrosis

Back 107

most commonly appears in pts between 40 and 70 years old - presents as gradual increase of dyspnea on exertion with a dry, non-productive cough

late hypoxemia, cyanosis, clubbing

unpredictable course, usually with gradual deterioration of lung function, despite treatment

some run an acute course, getting worse very rapidly

mean survival is three years (pt needs a lung transplant)

Front 108

nonspecific interstitial pneumonia

Back 108

restrictive disease

usually presents between 46 and 55 years old

wastebasket diagnosis with much better prognosis than usual interstitial pneumonia

2 patterns:
(1) cellular pattern - mild-moderate chronic interstitial inflammation - can have patchy or uniform distribution (better px)
(2) fibrosing pattern - diffuse or patchy interstitial fibrosis w/ all lesions of same age

Sx: dyspnea and cough for several months

Front 109

cryptogenic organizing pneumonia (COP)

Back 109

aka bronchiolitis obliterans with organizing pneumonia (BOOP)

Sx: cough, dyspnea

subpleural or peribronchial patchy areas of consolidation (loose plugs of organizing connective tissue in alveolar ducts, alveoli, bronchioles) that are all the same stage

underlying architecture is normal

occasionally there is spontaneous recovery, but usually pts need steroids for at least 6 months

Front 110

lung and collagen vascular disease

Back 110

various patterns of interstitial pneumonias

scleroderma usually non-specific interstitial pneumonia pattern

SLE - can have transient patchy lung infiltrates that disappear and reappear

RA - lung involvement is fairly common
- chronic pleuritis
- diffuse interstitial pneumonia and fibrosis
- rheumatoid nodules in lung, common in subQ tissue
- pulmonary HTN
- 30-40% of RA pts have abnormal PFTs

Front 111

pneumoconioses

Back 111

reaction of lungs to inhalation of mineral dusts in the workplace (anthracosis, silicosis, asbestosis, etc.) or organic or inorganic particulates or chemical fumes or vapors

Front 112

on what does development of pneumoconiosis depend?

Back 112

1) amount of dust retained in lung ([dust] in ambient air, duration of exposure, effectiveness of clearance, depressed mucociliary clearance)
2) size of particles (1-5um reaches small airways and air sacs and settle into linings)
3) particle solubility and reactivity
4) additional effects of other irritants

Front 113

particle solubility and reactivity

Back 113

smaller particles have larger surface area-to-mass ratio and are more likely to cause acute lung injury

larger particles resist dissolution and can persist for years in parenchyma, evoking fibrosing pneumoconioses

quartz particles can cause direct tissue injury via free radicals and can trigger macrophages to release inflammatory and fibroblastic mediators

Front 114

coal workers' pneumoconiosis (CWP)

Back 114

reaction of lungs to inhaled coal

can be asymptomatic anthracosis w/o perceptible cell reaction, or a simple CWP w/ little lung dysfunction, or complicated/progressive massive fibrosis (PMF)

<10% of simple CWP progresses to PMF

Front 115

progressive massive fibrosis (PMF)

Back 115

generic term for confluent, fibrosing reaction in the lung that can be a complication of any of the pneumoconioses

most common in coal workers' pneumoconiosis and in silicosis

Front 116

anthracosis

Back 116

carbon ingested by macrophages accumulates in connective tissue along lymphatics and in hilar lymph nodes

gross morphology, see linear streaks and black nodes

seen in coal workers, urban dwellers, and smokers

Front 117

simple coal workers' pneumoconiosis

Back 117

1-2mm coal macules (of carbon-laden macrophages and small amounts of collagen) and larger nodules that can be confluent

most lesions are adjacent to respiratory bronchioles where the coal dust accumulates

the upper lobes and upper parts of the lower lobes are more affected

can progress to complicated CWP

Front 118

complicated coal workers' pneumoconiosis

Back 118

progresses from simple coal workers' pneumoconiosis (in <10% of cases nowadays)

takes years of exposure, but stopping exposure doesn't help at this point

multiple black scars 2-10cm

Sx: lung dysfunction, pulmonary HTN, cor pulmonale

microscopic: dense collagen and pigment often with a necrotic center of central ischemia

Front 119

for what diseases are pts with coal exposure at increased risk?

Back 119

chronic bronchitis
emphysema

Front 120

silicosis

Back 120

reaction of lungs to inhaled crystalline silicon dioxide (silica)

most prevalent of chronic occupational diseases worldwide

need decades of exposure - sandblasters and mineworkers; less commonly, months to years of exposure can cause acute silicosis

Front 121

pathogenesis of chronic silicosis

Back 121

crystalline forms (e.g. quartz) are much more fibrogenic than amorphous forms

macrophages that ingest silica release mediators (TNF, O2 derived free radicals, IL-1, fibrogenic cytokines, fibronectin, lipid mediators) before they die b/c silica is toxic to macrophages

reduced fibrogenic effect if mixed with other minerals and quartz; in workplace is rarely pure so is less dangerous

Front 122

gross morphology of chronic silicosis

Back 122

early lesions in upper lung zones

tiny, just palpable nodules that are pale to black (if mixed with coal) and coalesce into hard, fibrotic scars that can have some central softening and cavitation due to superimposed TB/ischemia

can get fibrotic lesions in nodes or pleura

nodes can get eggshell calcification

late in course, progresses to progressive massive fibrosis (PMF)

Front 123

microscopic morphology of chronic silicosis

Back 123

nodular lesions consisting of concentric layers of hyalinized collagen with capsule of even more condensed collagen

birefringent silica revealed by polarized microscopy

Front 124

clinical features of silicosis

Back 124

usually pick up as an Xray finding (fine nodularity in early stages) in asymptomatic pts
- pulmonary function tests are normal or only moderately abnormal

don't become dyspneic until progressive massive fibrosis (PMF), at which point stopping exposure usually doesn't help

increased susceptibility to TB
controversial cancer association

Front 125

asbestosis

Back 125

lung reaction to inhalation of asbestos

2 forms:
(1) serpentine - curly, flexible fibers
(2) amphibole - straight, stiff, brittle fibers - more pathogenic

initial injury at bifurcation of small airways and ducts where fibers land and penetrate; macrophages try to ingest and clear, but then release chemotactic and fibrogenic mediators

eventually generalized inflammation and interstitial fibrosis is diffuse rather than the nodular pattern in silicosis

asbestos is both a tumor promoter and initiator

Front 126

forms of asbestosis

Back 126

1) serpentine - curly, flexible fibers
- most of industrial asbestos
- more apt to be trapped and removed in URT
- more soluble, so eventually leached from tissue

2) amphibole - straight, stiff, brittle fibers
- more pathogenic, esp regarding mesothelioma
- can get into deep lung, penetrate epithelium, and reach interstitium

Front 127

asbestos as a tumor promoter and initiator

Back 127

synergistic with other carcinogens

asbestos exposure alone increases risk of bronchogenic CA 5x more than non-smoking population

Front 128

gross morphology of asbestosis

Back 128

diffuse interstitial fibrosis that starts in lower lobes and subpleura and then progresses to middle and upper lobes

see a thick visceral pleura

pleural fibrous plaques are the most common manifestations of asbestos exposure
- well circumscribed, dense collagen
- often have calcium
- located on anterior and posterolateral parietal pleura as well as on the diaphragm
- no asbestos bodies

uncommonly induce pleural effusions

Front 129

manifestations of asbestosis

Back 129

pleural effusions (uncommon)
bronchogenic CA
mesothelioma

Front 130

what is mesothelioma?

Back 130

a rare tumor of the lungs with 1000x greater risk in populations exposed to asbestos

smoking is not contributory

Front 131

microscopic morphology of asbestosis

Back 131

asbestos bodies - gold-brown, fusiform or beaded rods with translucent centers
- asbestos fiber coated with Fe-containing proteinaceous material

fibrosis starts around resp. bronchioles and alveolar ducts, extends into sacs and spaces and causes enlarged air spaces with thick fibrous walls

end result is honeycomb lung

Front 132

what are asbestos bodies?

Back 132

gold-brown, fusiform or beaded rods with translucent centers

consist of asbestos fiber coated with Fe-containing proteinaceous material

Fe is derived from ferritin of macrophages trying to phagocytose asbestos fiber

ferruginous bodies are similar - Fe-coatedparticles, but with no distinctive core

Front 133

clinical features of asbestosis

Back 133

starts with exertional dyspnea with a productive cough which then progresses

rare before 10 years after first asbestos exposure; more commonly presents at 20 years or more after first asbestos exposure

can be static or progressive to CHF, cor pulmonale

pleural plaques are asymptomatic

Front 134

what chemotherapy drug is directly toxic to the lungs?

Back 134

bleomycin

Front 135

what pulmonary side effect is associated with amiodarone?

Back 135

pneumonitis (5-15% of pts)

Front 136

pulmonary complications of radiotherapy

Back 136

radiation pneumonitis, mostly to lung with radiation port

acute disease in 10-20% of pts 1-6 months after therapy
- fever, dyspnea, effusion, infiltrates
- may respond to steroids or progress to chronic disease

chronic disease - fibrosis
- looks like diffuse alveolar damage
- severe epithelial atypia
- foam cells in vessel walls

Front 137

sarcoidosis

Back 137

systemic disease with unknown cause

causes noncaseating granulomas in many organs; causes lung involvement and/or hilar adenopathy in 90%

diagnosis of exclusion (must rule out TB, fungal infections, beryllosis)

more prevalent in women, 10x more common in blacks than whites, more prevalent in SE US

Front 138

pathogenesis of sarcoidosis

Back 138

disordered immune regulation in a genetically predisposed pt who is exposed to unknown environmental agents

local immune abnormalities around granuloma (inc. CD4 T cells, inc. levels of TH1-derived cytokines, inc. levels of TNF)

systemic immune abnormalities: anergy to common skin test Ags, polyclonal hypergammaglobulinemia

genetic: association with HLA-A1 & HLA-B8

environmental: mycobacteria, rickettsia, propionibacterium acnes

Front 139

what kind of T cell population is found in sarcoidotic granulomas?

Back 139

oligoclonal CD4 T cell proliferation, rather than polyclonal

Front 140

what manifestation of hyper T-cell dysregulation is common in sarcoidosis patients?

Back 140

polyclonal hypergammaglobulinemia

Front 141

microscopic morphology of sarcoidosis

Back 141

non-caseating granulomas composed of tightly clustered epitheloid cells

langhans cells (horseshoe nuclei) or foreign body type giant cells

may be replaced by hyalinized scars

laminated concretions - Schaumann bodies
Stellate inclusions - ateroid bodies within giant cells

Front 142

effects of sarcoidosis on the lungs

Back 142

microscopic disease or coalesced granulomas up to 2cm usually located along the lymphatics around bronchi and vessels

often see multiple lesions in varying stages of development

lesions heal with fibrosis and hyalinization in time

CD4/CD8 ratio > 2.5

Front 143

effects of sarcoidosis on the lymph nodes

Back 143

lymphadenopathy of hilar and mediastinal lymph nodes, but can involve others

nodes can be calcified

tonsils are involved in 1/4-1/3 of pts

Front 144

effects of sarcoidosis on the spleen and liver

Back 144

microscopic disease in 75%
gross splenomegaly in 20%

liver affected less often
- usually scattered granulomas in the portal triads rather than parenchyma

Front 145

effects of sarcoidosis on bone marrow

Back 145

affects bone marrow in 20% of pts

particular affinity for phalanges

causes small areas of resorption within marrow cavity or a diffuse reticulated pattern throughout the cavity

Front 146

effects of sarcoidosis on the skin

Back 146

30-50% of pts

varying appearance:
- nodules
- plaques
- lupus type

Front 147

effects of sarcoidosis on the eye, lacrimal glands, and salivary glands

Back 147

affects 20-50% of pts

can cause glaucoma or blindness

if eye is involved, the lacrimal gland is often inflamed and producing a decreased amount of tears

if bilateral salivary glands are affected, can cause Mikulicz syndrome

Front 148

effects of sarcoidosis on muscle

Back 148

weakness, tenderness, aching, fatigue

Front 149

clinical features of sarcoidosis

Back 149

protean/variable manifestations

resp. Sx: SOB, cough, hemoptysis
systemic Sx: fever, fatigue, wt loss, night sweats

unpredictable course (progressive, relapsing/remitting, or permanent remission occasionally by steroids or spontaneous)

70% recover or have min manifestations
20% have some permanent loss of lung or visual fcn
10% die of progressive pulmonary fibrosis or other organ damage

less amount of disease at time of dx, the better the prognosis

Front 150

hypersensitivity pneumonitis

Back 150

immunologically mediated, predominantly interstitial disorder with alveolar involvement caused by prolonged exposure to inhaled organic dusts or other occupational antigens

early removal of agent prevents progression to chronic fibrotic disease

early lesions are type III and later granulomas are type IV hypersensitivity reactions

Examples: farmer's lung, pigeon breeder's lung, humidifier/air conditioner lung

Front 151

farmer's lung

Back 151

type of hypersensitivity pneumonitis caused by actinomycetes in humid warm hay

Front 152

pigeon breeder's lung

Back 152

type of hypersensitivity pneumonitis caused by inhalation of antigens from the serum, excretions, or feathers of birds

Front 153

humidifier/air conditioner lung

Back 153

type of hypersensitivity pneumonitis caused by a thermophilic bacteria

Front 154

immunologic abnormalities seen in hypersensitivity pneumonitis

Back 154

acute phase - inc. of proinflammatory chemokines IL8 and MIP1alpha

inc in numbers of CD4 T cells and CD8 T cells

most pts have specific Abs to the causative agent in serum, suggestive of a type III hypersensitivity

complement & Igs within vessel walls

Front 155

microscopic morphology of hypersensitivity pneumonitis

Back 155

interstitial pneumonitis (lymphocytes, plasma cells, and macrophages)
noncaseating granuloma
intraalveolar infiltrate

late - interstitial fibrosis and obliterative bronchiolitis

Front 156

clinical features of hypersensitivity pneumonitis

Back 156

acute - recurring attacks of fever, dyspnea, cough, elevated wbcs
- diffuse & nodular Xray infiltrates
- restrictive PFT pattern
- usually occurs 4-6 hours post-exposure

chronic - no acute exacerbations, but progressive resp. failure
- looks like other restrictive diseases

Front 157

what are the five categories of restrictive pulmonary diseases?

Back 157

(1) fibrosing diseases
(2) granulomatous disease
(3) pulmonary eosinophilia
(4) smoking-related interstitial diseases
(5) pulmonary alveolar proteinosis

Front 158

acute eosinophilic pneumonia with respiratory failure

Back 158

rapid onset of fever, dyspnea, and hypoxia; Xray shows diffuse infiltrates

unknown cause

fluid from a bronchioalveolar lavage is > 25% eosinophils

responds quickly to steroids

Front 159

simple pulmonary eosinophilia

Back 159

benign transient lung lesions with accompanying eosinophilia in the blood

Xray shows irregular densities

lung septae are thickened by eosinophils and occasional giant cells

no vasculitis, fibrosis, or necrosis

Front 160

chronic eosinophilic pneumonia

Back 160

aggregates of lymphocytes and eosinophils in septal walls and alveolar spaces mostly in peripheral lung

pt presents with fever, night sweats, and dyspnea

responds to steroids

diagnose after excluding other entities

Front 161

desquamative interstitial pneumonitis

Back 161

aggregates of macrophages in alveoli (not desquamated epithelial cells)

slow development of cough, dyspnea, and eventually severe respiratory embarassment (distress/failure)

Xray shows ground glass infiltrate in BOTH lower lobes caused by pneumocytic hyperplasia

Front 162

microscopic morphology of desquamative interstitial pneumonitis

Back 162

large numbers of macrophages with abundant cytoplasm and brown pigment (smokers' macrophages), some with finely granular iron and others with lamellated surfactant bodies

septae are thickened by sparse mononuclear inflammation

hyperplasia of epithelial cells (pneumocytes)

no interstitial fibrosis or mild at worst

Front 163

clinical features of desquamative interstitial pneumonitis

Back 163

pts present in the 4th-5th decade as dyspnea and a dry cough developing over wks to mos, as well as clubbing of digits

PFTs show mild restriction

ALL pts are cigarette smokers and most are males (2:1)

responds to steroids (and if pt concurrently stops smoking, response is 100%)

Front 164

respiratory bronchiolitis-associated interstitial lung disease

Back 164

pt presents with mild dyspnea and cough, as well as a hx of smoking >30 pack-years

pigmented intraalveolar macrophages are found in the 1st-2nd order respiratory bronchioles and aggregates of smokers' macrophages in respiratory bronchioles, alveolar ducts, and peribronchiolar spaces

patchy submucosal and peribronchiolar chronic inflammation/infiltrates with mild peribronchiolar fibrosis

pt may have mild centrilobular emphysema

quitting smoking improves condition but findings are similar btwn smokers & non-smokers

Front 165

pulmonary alveolar proteinosis

Back 165

rare pulmonary restrictive disease caused by abnormal accumulation of surfactant within the alveoli, interfering with gas exchange

Xray: patchy asymmetric opacification
Histo: accumulation of a-cellular surfactant

Front 166

acquired pulmonary alveolar proteinosis

Back 166

anti-GM-CSF antibody impairs surfactant clearance by alveolar macrophages

recurs in patients, even with lung transplants, because antibody is produced systemically

accounts for 90% of cases of PAP

Front 167

congenital pulmonary alveolar proteinosis

Back 167

presents as immediate onset of neonatal respiratory distress; is rapidly progressive and fatal if pt doesn't get a transplant by 3-6 months

associated gene mutations:
- ATP-binding cassette A3 (ABCA3) - most common
- surfactant proteins B & C
- GM-CSF & GM receptor beta chain
- GM receptor

Front 168

secondary pulmonary alveolar proteinosis

Back 168

VERY uncommon restrictive pulmonary disease

presents in patients with inhalational syndromes, including acute silicosis, as well as in patients with immunodeficiencies, malignancies, hematopoietic disorders, or lysinuric protein intolerance

Front 169

morphology of pulmonary alveolar proteinosis

Back 169

gross - marked increase in size and weight of lung, with turbid fluid exuding from involved areas

micro - accumulation of homogeneous, dense, granular material with lipid and cholesterol clefts, as well as PAS-positive material in alveolar spaces
- confluent consolidation of large areas, with no inflammation
- involved alveoli have hyperplastic pneumocytes and focal areas of necrosis

Front 170

clinical features of pulmonary alveolar proteinosis

Back 170

cough (may produce chunks of gelatinous material)

ranges from benign with eventual resolution to resp. insufficiency

pts are at risk for infections

treat with whole lung lavage and 50% respond to GM-CSF administration

Front 171

pulmonary embolism (PE)

Back 171

occlusion of large pulmonary arteries is nearly always caused by a thromboembolism (95% originate in deep veins of the legs)

responsible for >50,000 deaths/year and is the sole or major contributor in 10% of acute hospital deaths

Front 172

pathogenesis of pulmonary embolism (PE)

Back 172

pt almost always has an underlying disorder or is ill or has a hypercoagulable state

primary - thrombus builds up in veins via coagulation cascade

secondary - recent surgery, central lines, pregnancy or BCP, cancer, or obesity

Front 173

morphologic changes caused by a large saddle embolus in the pulmonary artery (or major branches)

Back 173

often associated with acute cor pulmonale and no other changes because the patient often dies very quickly

Front 174

gross morphology of small

Back 174

smaller emboli travel further through the pulmonary artery system into more peripheral vessels
- no infarction if there is adequate bronchial arterial circulation
- infarction results if bronchial system circulation is inadequate (i.e. pts with heart/lung disease)

infarction occurs with about 10% of emboli; can be multiple lesions of variable size, most of the time located in the lower lobes
- infarct is triangular with the apex pointing toward the hilum and extending to the lung periphery (occluded vessel is near the apex); it eventually shrinks and is replaced by a grey-white scar
- if hemorrhagic, appears as a raised red-blue area
- adjacent pleura often has fibrinous exudate

Front 175

what important feature distinguishes a pre-mortem clot (PE) from a post-mortem clot?

Back 175

lines of Zahn are found in pre-mortem clots, but not in post-mortem clots

Front 176

microscopic morphology of PE

Back 176

thromboembolus found in vessel

if there is an infarct, see ischemic necrosis in an area of hemorrhage

if the embolus was infected, the infarcted area will have intense inflammation (septic infarct) and may form an abscess

Front 177

clinical features of PE

Back 177

large embolus can cause instantaneous death
- during CPR, may restore rhythm on EKG, but not pulses b/c of massive circulatory block

smaller embolus in a normal person presents as transient chest pain, cough if there's hemorrhage w/o infarct and presents as chest pain, cough, hemoptysis, dyspnea, tachypnea, and fever (possibly with pleuritis and friction rub) if PE causes infarct

after first embolus, there is about a 30% chance of developing a second embolus

Front 178

what are the complications of multiple small pulmonary emboli?

Back 178

long-term pulmonary HTN
chronic cor pulmonale

Front 179

clinical Dx of PE

Back 179

Xray: wedge-shaped infiltrate at 12-36 hours if PE causes infarct

lung scan: ventilation/perfusion discrepancy; abnormality on angiography

D-dimer testing: elevated

Front 180

Tx for PE

Back 180

prevention: mechanical (early ambulation post surgery), anticoagulation if pt is high risk, vena caval filters

Tx of established emboli: anticoagulation (heparin, etc.), and thrombolysis in some

Front 181

in what patients do you see in situ pulmonary thrombosis?

Back 181

in situ thrombosis is rare, but is seen in pts with pulmonary HTN, pulmonary atherosclerosis, and heart failure

Front 182

pulmonary hypertension

Back 182

normal pulmonary pressure = 1/8 of systemic
considered pulmonary HTN when pressure = 1/4 of systemic

primary is idiopathic, is uncommon, and is usually sporadic (though 5% is familial with incomplete penetrance)

secondary is more common and has several causes

Front 183

causes of secondary pulmonary hypertension

Back 183

(1) chronic obstructive or interstitial lung diseases (inc. pulmonary arterial resistance)
(2) congenital/acquired heart disease (mitral valve stenosis)
(3) recurrent thromboemboli (dec. in functional x-sectional area of pulmonary vascular beds with inc. in pulmonary vascular resistance)
(4) autoimmune diseases involving pulmonary vasculature
(5) obstructive sleep apnea associated with obesity
(6) bush tea (contains crotalaria spectabilis, a plant in the tropics)
(7) prescription appetite depressant drugs (aminorex)
(8) prescription antiobesity drugs (fenfluramine & phentermine or fen-phen)

Front 184

pathogenesis of primary familial pulmonary hypertension

Back 184

caused by mutations in bone morphogenic protein receptor type 2 (BMPR2)

without BMP-BMPR2 signalling in vascular smooth muscle, have muscle proliferation

loss of a single allele causes disease state (dominant negative; loss of second allele may occur in vascular wall), but only in 25-50% of pts (incomplete penetrance b/c of modifier genes and/or environmental triggers

Front 185

what is BMPR2?

Back 185

bone morphogenic protein receptor type 2

a member of the TGF-beta receptor superfamily that binds TGF-beta and bone morphogenic peptide (BMP)

BMP-BMPR2 signalling is important in embryogenesis, apoptosis, cell proliferation, and cell differentiation (effects depend on environment; in vascular smooth muscle, favors apoptosis)

mutated in 50% of primary familial pulmonary hypertension and in 25% of primary sporadic pulmonary hypertension

Front 186

pathogenesis of secondary pulmonary hypertension

Back 186

dysfunction of endothelial cells results in release of products promoting vasoconstriction or causing platelet activation/adhesion (growth factor & cytokine release can induce migration/proliferation of smooth muscle)

in pts with a spastic component, vascular resistance can be decreased with vasodilators

Front 187

gross morphology of pulmonary hypertension

Back 187

many organizing or recanalized thrombi in PE

coexistence of emphysema, diffuse fibrosis, and/or chronic bronchitis implicates hypoxia as the cause

right ventricular hypertrophy

Front 188

microscopic morphology of pulmonary hypertension

Back 188

atheromatous deposits in large vessels

medial hypertrophy of muscular and elastic arteries at any level, but most prominent in small arteries and arterioles
- medial muscular hypertrophy
- intimal fibrosis
- pinpoint lumen
- best developed in primary disease

pts with primary pulmonary hypertension can develop plexogenic pulmonary arteriopathy - capillary tufts spanning the lumen of a dilated, thin-walled artery

Front 189

plexogenic pulmonary arteriopathy

Back 189

capillary tufts spanning the lumen of a dilated, thin-walled artery

present in:
(1) primary pulmonary hypertension
(2) congenital heart disease with L-R shunt
(3) drugs
(4) HIV

Front 190

clinical features of pulmonary hypertension

Back 190

signs/symptoms only present with advanced disease

primary is most common in females btwn 20-40 (presents as dyspnea and fatigue with occasional anginal-type pain)

progresses to respiratory distress, cyanosis, and right ventricular hypertrophy

death occurs in 2-5 years in 80% of pts from decompensated cor pulmonale often with pneumonia and thromboemboli

Front 191

goodpasture syndrome

Back 191

simultaneous proliferative glomerulonephritis and necrotizing hemorrhagic intersitial pneumonia

usually presents in males in their teens-20s

usually begins with hemoptysis and consolidations on Xray and then progresses to renal disease which may cause rapid renal failure

uremia is the usual cause of death

Front 192

pathogenesis of goodpasture syndrome

Back 192

antibodies are formed against the noncollagenous domain of alpha-3 chain of collagen IV

antibodies cause inflammatory destruction in glomerular and pulmonary basement membranes

trigger is unknown, but involved epitopes are normally hidden, so environmental triggers (viral infections, hydrocarbon solvent, cigarette smoke) must expose them

associated with HLA subtypes

Front 193

effects of goodpasture syndrome on lungs

Back 193

necrotizing hemorrhagic interstitial pneumonia

heavy lungs with areas of red-brown consolidation
- focal acute necrosis of alveolar walls
- intra-alveolar hemorrhage (with organization and hemosiderin-laden macrophages)
- pneumocyte hyperplasia
- fibrous thickening of septa

on immunofluorescence see linear deposits of Ig along basement membranes of septal walls

Front 194

effects of goodpasture syndrome on kidneys

Back 194

proliferative glomerulonephritis

- in early cases, focal proliferative glomerulonephritis
- in rapidly progressing glomerulonephritis, see crescentic glomerulonephritis

linear immunofluorescence for Ig and complement

Front 195

clinical features of goodpasture syndrome

Back 195

simultaneous proliferative glomerulonephritis (kidney problems) and necrotizing hemorrhagic interstitial pneumonia (lung problems)

seen in males in teens to 20s
Sx: hemoptysis and renal failure
Xray: consolidations

treat with plasma exchange to remove Abs and chemical mediators from circulation or with immunosuppression

Front 196

idiopathic pulmonary hemosiderosis

Back 196

insidious onset of productive cough, hemoptysis, anemia, and weight loss

intermittent, diffuse alveolar hemorrhage with diffuse infiltrate similar to Goodpasture Syndrome, but seen in younger adults and children

cause is unknown

responds to long term steroids/immunosuppression

some pts develop other autoimmune problems in the long term

Front 197

morphology of idiopathic pulmonary hemosiderosis

Back 197

gross - moderate increase in weight of lung with areas of red to red-brown consolidation

microscopic - varying hemorrhae and hemosiderosis in septa and in macrophages in alveolar spaces
- hyperplasia of type 2 pneumocytes
- varying interstitial fibrosis
- no inflammation (no anti-basement membrane antibodies detected)

Front 198

wegener granulomatosis

Back 198

autoimmune disease involving upper respiratory tract and lung, as well as other organs

Sx: hemoptysis

capillaritis and scattered, poorly formed granulomas (granulomas are well formed in sarcoidosis)

sometimes lung is the only available tissue for biopsy

Front 199

what are the nasal defense mechanisms against infections? how are they impaired?

Back 199

sneezing and blowing
protects from larger particles (>10um in diameter)

impaired by lack of cough reflex (can be caused by coma, drugs, and chest pain)

Front 200

what are the tracheobronchial defense mechanisms against infections? how are they impaired?

Back 200

mucociliary action
protects from particles 3-10um in diameter

impaired by impaired ciliary function (caused by cigarette smoke or genetic defect) or destruction of epithelium (caused by viral disease)

Front 201

what are the alveolar defense mechanisms against infections? how are they impaired?

Back 201

macrophages
protects from particles 1-5um in diameter

impaired by EtOH, smoking, anoxia, too much O2, congestion/edema, accumulation of secretions (cystic fibrosis & bronchial obstruction), and atelectasis

Front 202

what causes most pneumonias?

Back 202

inhalation of organisms

minority are secondary seeding from another site of infection

Front 203

what are the predisposing factors for community-acquired pneumonia?

Back 203

extremes of age (very young or very old) and other immunocompromised pts

lack/loss of spleen

chronic diseases

Front 204

streptococcus pneumoniae (pneumococcus)

Back 204

most common cause of community-acquired pneumonia

gram-pos diplococci

more penicillin resistant strains cause pneumonia

important to give vaccines to pts at high risk

Front 205

what is the most common cause of community-acquired pneumonia?

Back 205

streptococcus pneumoniae (pneumococcus)

Front 206

haemophilus influenzae

Back 206

gram-neg bacillus that commonly colonizes the URT

causes life-threatening pneumonias (high mortality) and meningitis in young children; causes community-acquired acute pneumonia in adults (common infection; not as severe)

most common bacterial cause of acute exacerbation of COPD

smaller bronchi are involved in pneumonia
- plugged by fibrinopurulent exudate
- pneumonia is usually lobular and patchy (occasionally lobar)

Front 207

what is clinically important about the encapsulated vs. non-encapsulated forms of H. influenzae?

Back 207

encapsulated form dominates unencapsulated by secreting haemocin, which kills the unencapsulated form

with vaccines, infections with the unencapsulated forms (otitis media, sinusitis, bronchopneumonia) are increased

survival in bloodstream correlates with presence of capsule (prevents opsonization & phagocytosis)

Front 208

what is the most common bacterial cause of acute exacerbation of COPD?

Back 208

Haemophilus influenzae

2nd most common is Moraxella catarrhalis

Front 209

Moraxella catarrhalis

Back 209

gram-negative diplococcus

causes pneumonia, especially in the elderly, and causes otitis media in children

second most common bacterial cause of acute exacerbation of COPD

Front 210

Staphylococcus aureus (pulmonary)

Back 210

gram-pos cocci arranged in a cluster of grapes

often causes a secondary pneumonia following a viral respiratory illness

causes pneumonia (and bacterial endocarditis) in IV drug abusers

high incidence of complications (abscess, empyema)

Front 211

Klebsiella pneumoniae

Back 211

gram-neg bacillus

most frequent cause of gram-neg bacterial pneumonia

common in debilitated, malnourished pts (i.e. chronic alcoholics)

characteristic thick gelatinous sputum from a viscid capsular polysaccharide

Front 212

what is the most frequent cause of gram-neg bacterial pneumonia?

Back 212

Klebsiella pneumoniae

Front 213

Pseudomonas aeruginosa

Back 213

gram-negative bacillus

causes community-acquired pneumonia in cystic fibrosis patients; in other groups is more often a nosocomial pneumonia

common cause of pneumonia in neutropenic patients

likes to invade vessels and spread outside of the lungs, causing very fulminant septicemia

Front 214

Legionella pneumophila

Back 214

causes Legionnaires' disease
causes Pontiac fever (self-limiting URI)

tends to be found in water sources (cooling towers or tubing systems for domestic water supplies)

causes pneumonia in pts with other medical ailments (transplant pts and immunosuppressed pts)

mortality is up to 50% in immunosuppressed pts

Front 215

what are the two patterns of bacterial pneumonia?

Back 215

(1) bronchopneumonia (lobular) pattern
- patchy consolidation of acute suppurative inflammation
- caused by any organism, but most commonly P. aeruginosa (can be caused by S. aureus, S. pneumoniae, H. influenzae, coliforms)
(2) lobar pneumonia pattern
- infection of entire lobe (or at least a large part of one)
- usually (90-95%) caused by S. pneumoniae

Front 216

bronchopneumonia pattern of bacterial pneumonia

Back 216

lobular pattern formed by patchy consolidations of acute suppurative inflammation often extending to multiple lobes and/or bilateral lungs; tends to be basal b/c that's where the secretions gravitate

usually an extension of preexisting bronchitis/bronchiolitis

seen in infancy and in old age (can be a terminal event in old age)

any organism can produce this pattern, but P. aeruginosa is especially known for it and S. aureus, S. pneumoniae, and H. influenzae are common causes

Front 217

morphology of bronchopneumonia pattern of bacterial pneumonia

Back 217

gross - patchy, dry, granular, 3-4cm, grey-red to yellow consolidations of suppurative inflammation with poorly demarcated edges

micro - neutrophilic exudate in bronchi, bronchioles, and adjacent alveoli

Front 218

lobar pneumonia pattern of bacterial pneumonia

Back 218

infection of an entire lobe or at least a large part of one

may have associated pleuritis b/c the pleura is often involved (fibrinous rxn to underlying inflammation; may completely resolve or leave some fibrous thickening/adhesions)

90-95% caused by S. pneumoniae b/c the capsule is protective (type 3 is particularly virulent)
- occasionally caused by K. pneumoniae, P. aeruginosa, P. mirabilis

4 stages:
(1) congestion
(2) red hepatization
(3) grey hepatization
(4) resolution

Front 219

what are the four stages of the lobar pattern of bacterial pneumonia?

Back 219

(1) congestion - lung is heavy, boggy, and red and bacteria, but few WBCs are present (congestion and intra-alveolar accumulation of fluid)
(2) red hepatization - lung is firm, red, and airless (resembles liver); massive confluent exudation of wbcs, rbcs, and fibrin that completely fill alveolar spaces
(3) grey hepatization - lung is pale grey-brown, and dry; disintegration of rbcs and fibrinopurulent exudate persists
(4) resolution - exudate is enzymatically digested, resorbed by macrophages, and subsequently coughed up

Front 220

what are the complications of pneumonia?

Back 220

abscess (esp with K. pneumoniae and type 3 pneumococcus)

empyema (diffuse or localized spread of inflammation to pleural cavity)

fibrosis (organization without clearing)

dissemination to other organs (heart valves/brain)

Front 221

clinical features of bacterial pneumonia

Back 221

productive cough

abrupt high fever and chills

pleuritic pain and friction rub

Front 222

what is the most common organism that causes community acquired atypical pneumonia?

Back 222

mycoplasma

Front 223

what are the viral causes of pneumonia?

Back 223

influenza A & B
respiratory syncytial virus
adenovirus, rhinovirus
rubeola, varicella
chlamydia pneumoniae, coxiella burnetti

Front 224

gross morphology of atypical community acquired pneumonia

Back 224

variable distribution (patchy or lobar)

lungs red-blue, congested, and subcrepitant (less air)

pleuritis is infrequently associated with atypical pneumonia

**lack of alveolar exudate**
**no consolidation**
**moderate inc. in wbcs**

Front 225

microscopic morphology of atypical community acquired pneumonia

Back 225

interstitial pneumonia b/c inflammation is confined within the alveolar septae rather than exuding into alveolar spaces

wide, edematous septae

mononuclear inflammation (lymphocytes) causes alveolar-capillary block so that the air can't travel well

may or may not be proteinaceous material in alveolar space (may form hyaline membranes)

pt may have superimposed bacterial infection (esp. with flu virus)

Front 226

clinical features of atypical community acquired pneumonia

Back 226

variable from severe "chest cold" (walking pneumonia) to fatal disease, but is usually mild disease with very low mortality

may/may not have cough that produces moderate sputum

symptoms are out of proportion to clinical findings (i.e. pt can't catch their breath, but their lungs sound ok - b/c of alveolar-capillary block air can't travel well)

cold agglutinins present in serum of 50% of pts with mycoplasma pneumonia and of 20% of pts with adenoviral pneumonia

Front 227

influenza virus

Back 227

single-stranded RNA virus

nucleoproteins determine type (A/B/C) and surface lipid envelope containing hemaglutinin and neuraminidase determine subtype (H1-3 & N1-2)

type A is a major cause of epidemic and pandemic infections (b/c of genetic drift/shift respectively)

types B and C do not have genetic drift so they mostly infect children (one infection confers immunity)

Front 228

what is the function of hemagglutinin in the surface lipid envelope of influenza viruses?

Back 228

binds to sialic acid-containing proteins and lipids on host cells

mediates entry into cells

Front 229

what is the function of neuraminidase in the surface lipid envelope of influenza viruses?

Back 229

cleaves sialic acid residues from proteins and lipids on infected host cells so that new virions can be released from the host cells

Front 230

against what parts of the influenza virus does the host make antibodies?

Back 230

hemagglutinin
neuraminidase

**useful for vaccines - use the strains of flu that are prevalent in the winter months of the opposite hemisphere**

Front 231

antigenic drift vs. antigenic shift in influenza A virus

Back 231

drift: caused by mutations of hemagglutinin and neuraminidase
- causes epidemic infections

shift: caused by replacement of both hemagglutinin and neuraminidase through recombination of RNA segments with those of animal viruses
- causes pandemic infections
- humans have no protection

Front 232

how is the influenza virus cleared from host cells?

Back 232

cytotoxic T cells kill infected host cells

IFNalpha and IFNbeta stimulate macrophages to induce synthesis of Mx1, an intracellular anti-flu protein

Front 233

avian flu

Back 233

influenza virus type A H5N1

60% mortality in humans

spreads in wild/domestic birds/chickens and so far transmission is inefficient, but the fear is antigenic recombination with a flu strain highly infectious to humans

- virulent strains cause widespread infection (not just in the lung) because of its unusual hemagglutinin pattern that can be cleaved by ubiquitous proteases, allowing entry into and damage of cells of many organs
- less virulent strains are only cleaved by specific proteases in limited organs, esp. the lung

Front 234

morphology of influenza virus infection

Back 234

UPPER RESPIRATORY:
- mucosal hyperemia and swelling
- lymphoplasmacytic infiltrate
- excess mucus is secreted, which can cause plugging and lead to secondary baterial infection
- can get viral-induced tonsillitis in children

LOWER REPIRATORY:
- vocal cord swelling
- excessive mucus plugging leading to secondary bacterial infection of lung and/or atelectasis
- if more severe, causes accumulation of cell debris, fibrin, and inflammatory cells with obliterative bronchiolitis and permanent lung damage

Front 235

human metapneumovirus

Back 235

negative-sense single-stranded RNA of the paramyxovirus family

mostly causes URIs and LRIs in young children, the elderly, and the immunocompromised
- up to 20% of office/clinic resp. infections
- 5-10% of hospitalizations for resp. infections in kids
- clinically resembles RSV
- can get reinfections throughout life, especially in old people

doesn't culture well, so use PCR

Front 236

severe acute respiratory syndrome (SARS)

Back 236

travel-related atypical pneumonia caused by the SARS coronavirus (a positive-sense, enveloped RNA virus)

incubation period: 2-10 days
Sx: dry cough, malaise, myalgia, fever, chills

1/3 of pts improve; 2/3 progress to severe respiratory disease; 10% die

Dx: PCR detection of virus or by appearance of Abs (viral load peaks at 10 days but Abs may not be detected for 28 days)

Tx: no specific treatment

Front 237

history of SARS

Back 237

started in China (first cases probably caused by contact with civets, a type of wild cat), spread through parts of SE Asia, and then to Toronto; travel related

in 6 months, there were more than 8,000 cases and 775 deaths

Front 238

nosocomial pneumonia

Back 238

pulmonary infections acquired in the course of a hospital stay

often found in sick/immunosuppressed pts

pts on a ventilator are at a particularly high risk b/c the ventilator bypasses the defenses of the URT

common causative organisms: gram-neg rods (P. aeruginosa, enterobacteriaceae); S. aureus

S. pneumoniae is NOT a common pathogen to cause nosocomial pneumonia

Front 239

aspiration pneumonia

Back 239

common in debilitated or unconscious patients with repeated vomiting or abnormal gag/swallowing reflexes

combination of chemical pneumonia from stomach acid and bacterial pneumonia from oral flora

usually more than one organism (aerobes>anaerobes) is recovered from samples of sputum, etc.

can be fulminant and cause death, or can cause a lung abscess

Front 240

what is the frequent complication of aspiration pneumonia?

Back 240

abscess formation

Front 241

what is an abscess?

Back 241

localized suppuration characterized by necrosis of tissue

Front 242

what organisms cause abscesses in the lungs?

Back 242

S. aureus
S. pneumoniae
P. aeruginosa & other gram-neg bacteria

anaerobes from the oral cavity

Front 243

mechanisms of abscess formation

Back 243

1) aspiration of infective material (most common cause)
- alcoholics
- gingivodental sepsis
- condition that depresses cough reflex
- aspiration of gastric contents

2) antecedent bacterial infection (pneumonia)
- Klebsiella, S. aureus, type 3 Pneumococcus
- fungi

3) septic embolus from veins or right heart valves that travels to and becomes lodged in the lungs

4) neoplastic obstruction

5) primary cryptogenic abscess (no explanation for why it is there)

Front 244

gross morphology of an abscess

Back 244

range in size from mm's to 5 or 6 cm

if caused by aspiration, most often there is a single abscess on the right side

pneumonic/bronchiectatic abscesses are generally multiple and located in the basal regions

can be filled with debris or not, depending whether or not it can drain into air passages; if it is filled, often get a saprophytic (organisms that live off of dead material) infection also

can enlarge to be multilocular cavities (gangrene of the lungs)

Front 245

microscopic morphology of an abscess

Back 245

suppurative (accumulation of neutrophils) destruction of lung parenchyma

central cavitation with a rim of fibrous tissue

Front 246

clinical features of abscesses

Back 246

similar to bronchiectasis - cough & purulent sputum, fever, chest pain, weight loss, digital clubbing

in 10-15% of older patients, there is an underlying carcinoma (central tissue destruction with secondary abscess formation)

complications: spread to pleura/brain; amyloidosis (AA type)

Front 247

chronic pneumonia

Back 247

localized lesion in an immunocompetent pt with or without lymph node involvement

caused by TB or fungi (histoplasmosis/blastomycosis/coccidioidomycosis)
- chronic fungal pneumonia causes a granulomatous lung disease that resembles TB

Front 248

histoplasmosis

Back 248

caused by Histoplasma capsulatum (a thermally dimorphic fungus that infects macrophages)

yeast forms are phagocytosed by unstimulated macrophages, proliferate in the phagolysosome, and then lyse the host cell

infection is controlled by CD4 cells recognizing fungal cell wall antigens and heat shock proteins
- CD4 cells secrete IFNgamma to activate macrophages to kill yeast
- yeast stimulates TNF secretion by macrophages, which stimulates other macrophages to kill the organism

associated with inhalation of dust from soil contaminated with infected bird/bat droppings

common fungus in the Ohio-Mississippi river basins and the Caribbean

major opportunistic infection in patients with AIDS because they lack cellular immunity

Front 249

similarities and differentiation of histoplasmosis to TB

Back 249

similarities to TB:
- self-limited primary pulmonary involvement (coin lesions) with progressive secondary lung disease in the apices
- Sx: cough, fever, night sweats
- localized extra-pulmonary lesions
- disseminated disease in immunosuppressed

HOW TO DIFFERENTIATE:
- histoplasmin test (+ in histoplasmosis)
- ID organism in biopsy (not sputum)
- serologic tests

Front 250

morphology of histoplasmosis in otherwise healthy individuals

Back 250

healthy people: granulomas with caseous necrosis coalesce, producing large areas of consolidation or occasionally liquefy into cavities

lesions fibrose and calcify to give a tree bark appearance (concentric lamination)

organism may persist for years in the 3-5um thin walled yeast form

Front 251

morphology of histoplasmosis in chronic disease

Back 251

granulomas with caseous necrosis in the apex of the lung and/or in the hilar lymph nodes

progressively involves more and more of the lung

less cavity formation than in TB

Front 252

morphology of histoplasmosis in fulminant, disseminated disease state

Back 252

**present in immunosuppressed pts**

no granulomas form

macrophages filled with H. capsulatum organisms accumulate in multiple organs (not just the lung)

Front 253

blastomycosis

Back 253

caused by Blastomyces dermatidis (a soil inhabiting, thermally dimorphic fungus)

common in the central and SE United States, Canada, Mexico, Middle East, Africa, and India

organism is very difficult to isolate

takes three forms
(1) pulmonary disease
(2) rare primary cutaneous form from direct inoculation
(3) disseminated disease

Front 254

pulmonary disease caused by Blastomyces dermatidis

Back 254

abrupt onset of a productive cough, chest pain, fever, night sweats, chills, headache, chest pain, and abdominal pain

can have multilobular, perihilar, or miliary infiltrates, or multiple discrete nodules
- upper lobes are most often involved

see suppurative granulomas; macrophages have limited kill ability, so the organism persists and recruits neutrophils

can resolve, persist, or progress to chronic disease

Front 255

how does Blastomyces dermatidis appear in tissue?

Back 255

5-15um organisms with broad-based round budding and a thick, double-contoured wall

Front 256

primary cutaneous disease caused by Blastomyces dermatidis

Back 256

rare

caused by direct inoculation

marked epithelial hyperplasia
(mimicks squamous cell carcinoma)

Front 257

coccidioidomycosis

Back 257

caused by Coccidioides immitis (encapsulated fungus)

common in the SW and far west US, as well as Mexican

nearly everyone who inhales spores are infected (80% of ppl who live in endemic areas have pos. skin test) but most primary infections are asymptomatic
- 10% present with fever, cough, pleurisy, skin lesions, and lung lesions (San Joaquin Valley Fever)
- <1% present as disseminated infection affecting the skin and meninges

infective forms block phagosome/lysosome fusion so that they are resistant to intracellular killing

Front 258

San Joaquin Valley Fever

Back 258

airborne fungal infection caused by Coccidioides immitis (aka coccidioidomycosis)

presents with fever, cough, hemoptysis, pleurisy, skin lesions and lung lesions

Front 259

morphology of coccidioidomycosis

Back 259

granulomas are thick-walled spherules 20-60um filled with endospores

pyogenic rxn on rupture

arthrospores grown in culture are very infections

rarely causes progressive multisystem disease

Front 260

pneumonia in immunocompromised (AIDS) patients

Back 260

almost all get opportunistic infections, often Pneumocystis, but can also get "regular" infections (bacterial pneumonias are more common, more severe, and more often lead to bacteremia)

bacterial and TB infections are more likely with higher CD4 counts (>200)
- pneumocystis generally infects with CD4 counts <200 (cup/helmet-shaped)
- CMV and MAC generally infect with CD4 counts <50

not all infiltrates are pneumonias (kaposi sarcoma, lymphoma, etc.)

Front 261

lung transplants

Back 261

usually get only one lung so that the other can go to another patient; exception is bilateral chronic infection

1YS is 75%; 5YS is 50%; 10YS is 25%

infection prone

can undergo acute or chronic rejection

Front 262

to what infections are lung transplants prone?

Back 262

1) bacterial (most common in the first few weeks)
2) viral, esp. CMV (decreasing with prophylaxis; usually occurs btwn 3-12 mos)
3) pneumocystis (rare b/c of prophylaxis)
4) fungal (candida or aspergillus; common at the anastomosis btwn the lung and bronchi)

Front 263

what is the most common infection in the first few weeks after a lung transplant?

Back 263

bacterial infection

Front 264

acute rejection of lung transplant

Back 264

occurs wks to mos after transplant or later if immunosuppression is decreased

clinically similar to infection (distinguish with a biopsy)

mononuclear cell infiltrates around small vessels, in submucosa, or both

responds to steroids

Front 265

chronic rejection of lung transplant

Back 265

occurs in 50% of pts in 3-5 years

Sx: cough, dyspnea, irreversible dec. in PFTs

bronchiolitis obliterans (obstruction of small airways by fibrosis with/without active inflammation)
- often very patchy, so a biopsy may not show it

cellular rejection around vessels

Front 266

pulmonary carcinomas

Back 266

90-95% of lung neoplasms (most frequent fatal malignancy) 85% of lung carcinomas are in smokers or those who have recently quit

highly associated with smoking

in males, the incidence & mortality is declining; in females, incidence has plateaued by mortality is still increasing

most common btwn 40 and 70 years old, peaking in 50s-60s

1YS=41%; 5YS=15%

Front 267

pathogenesis

Back 267

smoking is the biggest risk factor
- correlated with the amount of daily smoking, the duration of smoking, and the inhalation of smoke
- 10 yrs after quitting, risk is less, but still not to baseline
- cigar and pipe smoking inc. risk some, but not as much

women have greater susceptibility to tobacco carcinogens

97% of smokers have atypical cells in bronchial tree (vs. 1% of non-smokers)

Front 268

how does smoking affect the risk of developing a pulmonary carcinoma?

Back 268

average smoker has 10x risk

heavy smoker (2 packs/day) has 60x risk

Front 269

what are the risk factors for developing pulmonary carcinomas?

Back 269

smoking
radiation
asbestos
radon in homes

Front 270

what is the most frequent malignancy in asbestos exposure?

Back 270

lung cancer

latency of 10-30 years

Front 271

what dominant oncogenes are frequently involved in pulmonary carcinomas?

Back 271

c-MYC
K-RAS (non-small cell carcinoma)
EGFR (non-small cell carcinoma)
c-MET
c-KIT (overexpressed, not mutated, in small cell carcinoma)

Front 272

what tumor suppressor genes are commonly deleted in pulmonary carcinomas?

Back 272

p53 (small cell and non-small cell)
RB (small cell carcinoma)
p16/INK4alpha (non-small cell carcinoma)

Front 273

what are the genetic predispositions to pulmonary carcinomas?

Back 273

some alleles of CYP1A1 increase the ability to metabolize some precarcinogens, increasing risk of cancer

pts with lymphocytes that have chromosome breaks on exposure to tobacco carcinogens

Front 274

if not associated with smoking, in what gender are pulmonary carcinomas more frequent?

Back 274

women

mostly associated with EGFR mutations; KRAS & p53 mutations less so

Front 275

what mutations are common in small cell lung carcinoma?

Back 275

MYCN*
MYCL*
p53 3p
RB
BCL2*
c-KIT*

*= oncogenes

Front 276

what mutations are common in non-small cell lung carcinoma

Back 276

EGFR*
KRAS*
p53
p16/INK4alpha

*=oncogenes

Front 277

what are the precursors for lung carcinomas?

Back 277

squamous metaplasia
atypical metaplasia
dysplasia
carcinoma in situ

Front 278

what percentages of lung carcinomas are squamous cell? adenocarcinomas? small cell? large cell?

Back 278

type - M - F
squamous - 32% - 25%
adeno - 37% - 47%
small cell - 14% - 18%
large cell - 18% - 10%

Front 279

what is the most common form of lung carcinomas?

Back 279

adenocarcinoma

been increasing for past 20 years, until they are now the most common form, especially in females

Front 280

where do carcinomas tend to arise?

Back 280

in general, carcinomas tend to be central lesions, originating in the first-third order bronchi

they are more common closer to the hilus of the lungs

smaller numbers arise in the periphery, from alveolar septal cells or terminal bronchioles; these tend to be adenocarcinomas

Front 281

information about the development of lung carcinomas in general

Back 281

start as cytological atypia and progress to thickening or piling up of abnormal mucosa

excrescence that elevates or erodes lining epithelium

finally, several scenarios can occur:
1) grow into lumen of the bronchus and cause obstruction
2) penetrate into wall of bronchus and infiltrate peribronchial tissue into adjacent regions of the carina or mediastinum
3) grow into the parenchyma forming a broad intraparenchymal mass

Front 282

gross morphology of lung carcinomas

Back 282

firm or hard

grey-white

see hemorrhage or necrosis, especially when large (appear yellow-white and soft)

large tumors can cavitate at necrotic foci

Front 283

extension of lung carcinomas

Back 283

can breach pleura or pericardium

more than 50% have bronchial, hilar, or mediastinal node involvement

Front 284

distant spread of lung carcinomas

Back 284

lymphatic and hematogenous spread

spread early in the course of the tumor, except for squamous cell carcinoma which metastasizes outside the thorax late in the course

>50% have adrenal involvement
30-50% have liver involvement
20% have brain involvement
205 have bone involvement

Front 285

what characteristics are associated with patients who have squamous cell carcinoma of the lung?

Back 285

males

smokers

Front 286

gross morphology of squamous cell carcinoma of the lung

Back 286

tends to be central and located in large bronchi; peripheral forms are increasing in frequency

tumors are large

in general, local spread, but rapid growth counteracts the later metastases

metastases form later in the clinical course than in other types of lung carcinomas

Front 287

microscopic morphology of squamous cell lung carcinoma

Back 287

can be:
1) well differentiated:
- keratin and intercellular bridging
2) less differentiated:
- mix or cannot distinguish from adenocarcinoma
- MUST distinguish from small cell carcinoma

Front 288

molecular markers of squamous cell lung carcinoma

Back 288

higher frequency of p53 mutations than other mutations

loss of protein expression of RB and p16/INK4a genes

overexpression of EGFR

HER-2/neu is highly expressed

Front 289

general information about lung adenocarcinomas

Back 289

malignant epithelial tumor with glandular differentiation or mucin production

most common lung carcinoma, especially in females and non-smokers

slower growing than squamous cell carcinoma, but metastases are early and widely-spread

located more peripherally than are squamous cell carcinomas and are smaller

can be associated with a scar

Front 290

though adenocarcinomas are commonly associated with non-smokers, what percent of them are in smokers?

Back 290

75%

filters and low tar/nicotine in cigarettes allow for deeper inhalation, exposing more peripheral airways to the carcinogens

Front 291

microscopic morphology of lung adenocarcinomas

Back 291

vary from well-defined glands to papillary tumors to solid tumors with only a few mucin-producing cells

80% form and secrete mucin

most adenocarcinomas are TTF (thyroid transcription factor)-positive

Front 292

molecular markers of lung adenocarcinomas

Back 292

K-RAS mutations (associated with worse outcome and resistance to EGFR inhibitors)
p53 mutations
RB mutations
p16 mutations

Front 293

what pulmonary adenocarcinoma molecular marker is associated with a worse outcome and resistance to EGFR inhibitors?

Back 293

K-RAS mutations

EGFR mutations have improved survival if treated with EGFR inhibitors

Front 294

bronchioloalveolar subtype of pulmonary carcinomas are a subtype of what type of lung carcinoma?

Back 294

bronchioloalveolar carcinoma is a subtype of pulmonary adenocarcinoma that involves the pulmonary parenchyma in terminal bronchioalveolar regions

Front 295

general information about the bronchioloalveolar subtype of pulmonary adenocarcinomas

Back 295

subtype of adenocarcinomas that involves the pulmonary parenchyma in terminal bronchioalveolar regions that is probably derived from terminal bronchioles or the alveolar walls

constitutes 1-10% of lung cancers

if the lesion causes a dimple, it is more likely metastatic than primary; if the lesion causes a pucker in the lung, it is more likely primary than metastatic

Front 296

gross morphology of bronchioloalveolar subtype of adenocarcinoma

Back 296

located peripherally

can be one nodule, multiple nodules, or coalescent (looks more like pneumonia than a tumor)

parenchymal nodule is grey to grey-white, and depending on mucus production may or may not be translucent (translucent if mucus production is higher)

Front 297

microscopic morphology of bronchioloalveolar subtype of adenocarcinoma

Back 297

grows along pre-existing structures without destroying alveolar architecture (lines the alveolar sacs)

non-mucinous are formed by columnar or cuboidal cells; they tend to be peripheral nodules, amenable to excision (excellent 5YS)

mucinous are formed by tall columnar cells with cytoplasmic and intra-alveolar mucin; tend to spread aerogenously, with satellite tumors

classic adenocarcinoma can have bronchioloalveolar pattern at periphery

Front 298

clinical features of bronchioloalveolar subtype of pulmonary adenocarcinomas

Back 298

present anywher from 20s to late adulthood with equal sex distribution

presents with cough, hemoptysis, and pain

since it does not invade bronchi, no atelectasis/obstruction is seen (noninvasive tumor, so it kills by suffocation)

Front 299

large cell carcinoma

Back 299

10-15% of lung carcinomas

probably undifferentiated squamous cell or adenocarcinomas

one variant is a large cell neuroendocrine carcinoma
- organoid nesting, trabecular or rosette-like
- ultrastructural features of neuroendocrine glands
- 5YS is 27%; 10YS is 9%

Front 300

microscopic morphology of large cell carcinoma

Back 300

probably undifferentiated squamous cell or adenocarcinoma

larger, polygonal cells that have large vesicular nuclei and prominent nucleoli; have moderate cytoplasm

ultrastructure may show minimal glandular or squamous features

Front 301

small cell carcinoma of the lung

Back 301

aka oat cell carcinoma

20-25% of pulmonary carcinomas

highly malignant tumor of neuroendocrine origin, located in the hilar-to-central region of the lung

no precursor lesions (doesn't start out as carcinoma in situ)

can secrete various polypeptide hormones - common cause of paraneoplastic syndromes

HIGH association with cigarette smoking (only 1% occur in non-smokers)

Front 302

microscopic morphology of small cell carcinoma of the lung

Back 302

small (about 2x the size of a lymphocyte), round cells with little cytoplasm; the nucleus is filled with fine granular chromatin (in a salt & pepper pattern)

neuroendocrine markers are present on cells

cells have a high mitotic rate and nuclear molding is prominent

necrosis is a common feature, as is the "crush artifact"

Front 303

molecular mutations in small cell lung carcinoma

Back 303

p53 mutations in 50-80%
RB mutations in 80-100%

Front 304

clinical features of small cell lung carcinomas

Back 304

most aggressive lung tumors (if untreated, leads to rapid death in 6-16 weeks)

pts with these tumors are not surgical candidates metastases form early (most by time of dx); these carcinomas generally respond to radiotherapy/chemotherapy, but will recur

commonly see paraneoplastic syndromes

5YS = 9%, 10YS = 5%

Front 305

combined pulmonary carcinomas

Back 305

10% of lung carcinomas have histology of two or more carcinoma types

small cell carcinoma component
non-small cell component

Front 306

what changes in lung, distal to obstruction, are seen as secondary pathology to lung carcinomas?

Back 306

atelectasis (total obstruction)
emphysema (partial obstruction)
bronchitis or bronchiectasis due to impaired airway drainage
abscess

Front 307

what forms of secondary pathology are common to lung carcinomas?

Back 307

changes in lung distal to obstruction

superior vena cava syndrome

pancoast tumors

Front 308

superior vena cava syndrome

Back 308

compression of superior vena cava (commonly caused by pulmonary carcinomas), which causes circulatory compromise

Sx: dusky head and arm, with edema (venous congestion of head and arm)

Front 309

pancoast tumors

Back 309

apical carcinomatous lesions in the superior pulmonary sulcus

these lesions tend to invade neural structures around the trachea, including the cervical sympathetic plexus

see Horner syndrome (ptosis, miosis, enophthalmos, anhidrosis) on the side of the lesion and severe pain in an ulnar nerve distribution

Front 310

clinical course of pulmonary carcinomas

Back 310

common presenting symptoms: cough>wt loss>chest pain>dyspnea

central lesion dx by sputum cytology
peripheral lesion dx by FNA

can have the metastasis causing presentation (70-80% are not localized enough to be surgical candidates)

5YS=15% (if localized enough to be resected, 50% survival unless small cell)

Front 311

what paraneoplastic syndrome is caused by ADH?

Back 311

inappropriate ADH with hyponatremia

Front 312

what paraneoplastic syndrome is caused by ACTH?

Back 312

Cushing syndrome

Front 313

what paraneoplastic syndrome is caused by PTH or PTH-related peptide?

Back 313

hypercalcemia

Front 314

what paraneoplastic syndrome is caused by calcitonin?

Back 314

hypocalcemia

Front 315

what paraneoplastic syndrome is caused by gonadotropins?

Back 315

gynecomastia

Front 316

what paraneoplastic syndrome is caused by serotonin?

Back 316

carcinoid syndrome

Front 317

what paraneoplastic syndrome is caused by bradykinin?

Back 317

carcinoid syndrome

Front 318

what paraneoplastic syndromes are commonly caused by small cell lung carcinomas?

Back 318

ADH - inappropriate ADH with hyponatremia
ACTH - Cushing syndrome
serotonin - carcinoid syndrome
bradykinin - carcinoid syndrome

Front 319

what paraneoplastic syndromes are commonly caused by squamous cell lung carcinomas?

Back 319

PTH/PTH-related protein - hypercalcemia

Front 320

what paraneoplastic syndromes are commonly caused by carcinoid lung tumors?

Back 320

serotonin - carcinoid syndrome
bradykinin - carcinoid syndrome

Front 321

Lambert-Eaton Myasthenic Syndrome (LEMS)

Back 321

muscle weakness caused by autoantibodies against neuronal calcium channels

around 60% of those with LEMS have an underlying malignancy, most commonly small cell lung cancer and is therefore regarded as a paraneoplastic syndrome

Front 322

leukemoid reaction

Back 322

elevated WBC count (leukocytosis) that is a physiological response to stress or infection as opposed to a primary blood malignancy/leukemia

can be a paraneoplastic syndrome caused by primary lung cancers

Front 323

hypertrophic pulmonary osteoarthropathy

Back 323

aka Bamberger-Marie disease

clubbing of fingers and periostitis of the long bones of the upper and lower extremities

distal expansion of the long bones as well as painful, swollen joints and synovial villous proliferation are often seen

may be primary or may be a secondary paraneoplastic syndrome caused by diseases like lung cancer

Front 324

pulmonary neuroendocrine cell hyperplasia

Back 324

lesion that is secondary to airway fibrosis and/or inflammation

Front 325

diffuse idiopathic neuroendocrine cell hyperplasia

Back 325

rare pulmonary precursor lesion to multiple tumorlets and carcinoid tumors

Front 326

neuroendocrine tumorlets

Back 326

small, inconsequential hyperplastic nests of neuroendocrine cells in areas of scarring or inflammation

Front 327

bronchial carcinoid

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1-5% of lung tumors

usually present in patients younger than 40 years with equal distribution between the sexes

no environmental associations, including smoking

low-grade malignant lesions of epithelial origin that can be central or peripheral in the lungs

occasionally part of MENs

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gross morphology of bronchial carcinoid

Back 328

central lesions are spherical or occasionally finger-like masses usually no more than 4cm in diameter with intact mucosa that project into the lumen of a bronchus (usually main stem bronchi); less frequently they grow inward in peribronchial tissue as a collar button lesion (fan out in the peribronchial tissue)

peripheral lesions are solid and nodular

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microscopic morphology of bronchial carcinoid

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nests, cords, and masses of cells separated by delicate stroma

cells have uniform, round nuclei and moderate amounts of cytoplasm (they contain dense-core granules characteristic of neuroendocrine cells, serotonin, neuron-specific enolase, calcitonin, and other peptides)

rare mitoses are noted

if these lesions become more pleomorphic, they tend to behave more aggressively

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atypical bronchial carcinoids

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more likely to spread to lymph nodes than are other bronchial carcinoids

2-10 mitoses/hpf

foci of necrosis

p53 mutations, and abnormalities of BCL2 & BAX expression (not present in typical carcinoids)

5YS=56%
10YS=35%

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clinical features of bronchial carcinoids

Back 331

cough, hemoptysis, and impairment of drainage with resultant sequelae are caused by the intraluminal growth

carcinoid syndrome (intermittent attacks of diarrhea, flushing, and cyanosis) is rare, but is caused by the serotonin secretion

most follow a benign course and are resectable (10YS=85%); the atypical carcinoids can be locally invasive or metastasize (10YS=35%)

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pulmonary hamartoma

Back 332

fairly common benign tumor made mostly of mature hyaline cartilage with some epithelial clefts

usually found as an incidental coin lesion (<4cm rounded focus of radioopacity) on Xray

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inflammatory pulmonary myofibroblastic tumor

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rare tumor found in children

3-10cm grey-white round peripheral mass that consists of neoplastic fibroblasts, myofibroblasts, lymphocytes, and peripheral fibrosis

seen as a round peripheral mass on Xray; 25% have calcifications visible on the Xray

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metastatic tumors in the lungs

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the lungs are the most common site of metastasis from distant tumors; can also be invaded by neighbors (esophageal carcinomas and mediastinal lymphomas)

it is usual to have multiple discrete nodules, that tend to be peripheral, in all lobes (cannonball lesions)

a less frequent clinical presentation would be diffuse infiltration of the septae and connective tissue (occurs with lymphatogenous spread)

rarest presentation is seen in histology only as diffuse intralymphatic dissemination (no gross lesion is present)

if they involve the subpleural lymphatics, it is called lymphangitis carcinomatosa

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lymphangitis carcinomatosa

Back 335

diffuse infiltration and obstruction of pulmonary parenchymal lymphatic channels by tumor

involvement of subpleural lymphatics by metastases

Front 336

what is seen in the pleura as secondary involvement of an underlying disease?

Back 336

lung infections and adhesions are most common

Front 337

causes of effusions

Back 337

inc. hydrostatic pressure (CHF)
inc. vascular permeability (pneumonia)
dec. oncotic pressure (nephrotic syndrome)
inc. intrapleural negative pressure (atelectasis)
dec. lymphatic drainage (mediastinal carcinomatosis)

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inflammatory effusions

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aka pleuritis

can be serous, serofibrinous, fibrinous

caused by usual infections (pneumonia, TB, bronchiectasis, and abscess), by infarcts, by immune diseases, by radiation, or by metastatic disease

usually fairly mild, with resolution

more severe if empyema (frankly purulent exudate that consists of neutrophils) is formed

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what type of inflammatory effusion is caused by radiation?

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serofibrinous pleuritis

Front 340

empyema

Back 340

inflammatory pleural effusion that consists of frankly purulent exudate (pus - formed by neutrophils)

usually caused by bacterial or fungal seeding of the pleural space as a contiguous spread from an intrapulmonary infection; less often caused by lymphatic/hematogenous seeding

usually fairly small and localized, but harder than other effusions to resolve without formation of fibrous adhesions that can obliterate the pleural space/seriously restrict pulmonary expansion

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hemorrhagic effusions

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suspect malignancy
can be caused by bleeding disorders or rickettsial disease

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hemothorax

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noninflammatory pleural effusion that results from escape of blood into the pleural cavity, which forms large clots

caused by vascular trauma or ruptured aortic aneurysms

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hydrothorax

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noninflammatory pleural effusion

clear, straw-colored fluid accumulated in the pleural space

most common cause is CHF (leading to pulmonary congestion and edema) - usually presents bilaterally

can be caused by ovarian fibroma and ascites (Meig syndrome) - presents unilateral on the right

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meig syndrome

Back 344

triad of ascites, pleural effusion (hydrothorax), and benign ovarian tumor (fibroma)

for unknown reasons, the pleural effusion is classically unilateral, on the right side

syndrome resolves after resection of the ovarian tumor

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chylothorax

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noninflammatory pleural effusion

lymphatic fluid (chyle; milky white fluid) accumulated in the pleural space, more often seen on the left side

must distinguish from turbid serous fluid by letting stand (chylous fat will separate, but the serous fluid will not)

caused by thoracic duct trauma or lymphatic obstruction by a tumor

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what is a pneumothorax? what are the different kinds?

Back 346

accumulation of air/gas in the pleural space

- spontaneous
- traumatic
- therapeutic
- tension

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spontaneous pneumothorax

Back 347

most often caused by rupture of an alveolus associated with emphysema, asthma, or TB, but can be associated with abscess

spontaneous idiopathic pneumothorax occurs in young people as the result of a rupture of small subpleural apical blebs

commonly recurring

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traumatic pneumothorax

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caused by perforating injury to the pleura (and sometimes to the lung)

air enters the lung from outside the body

Front 349

for what illness would a therapeutic pneumothorax be created?

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used to be used as a treatment for TB

Front 350

tension pneumothorax

Back 350

caused by a ball valve effect in which air can enter the lung and/or pleural space with inspiration but cannot escape during expiration

progressive increase in pressure compresses the lung, mediastinum and opposite lung

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what type of tumors are more common in the pulmonary pleura?

Back 351

secondary tumors are much more common than primary

lung and breast metastases are especially common (they create serous or serosanguinous effusions)

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what are the two types of primary pleural tumors?

Back 352

solitary fibrous tumor (aka pleural fibroma) - benign

mesothelioma - malignant

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solitary fibrous tumor (pleural fibroma)

Back 353

primary tumor of the visceral pulmonary pleura

usually a benign lesion, but rarely a non-benign tumor with necrosis, mitoses, and pleomorphism

localized soft tissue tumor that lines the pulmonary pleura, ranges from a few cm to huge in size, and is often attached to the pleural surface by a pedicle (confined to the lung surface)

no association with asbestos

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morphology of solitary fibrous tumor (pleural fibroma)

Back 354

gross - dense fibrous tissue with occasional cysts filled with a viscid fluid

microscopic - whorls of reticulin and collagen with interspersed spindled cells looking like fibroblasts

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mesothelioma

Back 355

malignant tumor that arises from either visceral or parietal pleura

90% are associated with occupational exposure to asbestos (risk with exposure to asbestos is 7-10%); smoking does NOT increase risk

tumor takes 25-45 years after exposure to develop

diffuse tumor, spreading widely in the pleural space, usually associated with effusion

looks like the lung is sheathed in a thick layer of soft, gray-pink tumor

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microscopic morphology of mesothelioma

Back 356

mixture of 2 types of cells (either of which can predominate)
1) mesenchymal cells - resembles a spindle cell sarcoma (sarcomatoid type)
2) epithelial cells - more common - cuboidal to columnar cells can form glandular or papillary structures

difficult to distinguish from adenocarcinoma, especially if epithelial cells predominate

characteristic EM appearance with long microvilli and many tonofilaments

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what distinguishing markers are useful to distinguish mesothelioma from adenocarcinomas?

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acid mucopolysaccharide positive

negative for CEA and other adenocarcinoma markers

staining for keratin proteins is perinuclear in mesothelioma and peripheral in adenocarcinoma

immunohistochemistry:
- positive for calretinin
- positive for WT-1
- positive for cytokeratin 5/6

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clinical features of mesothelioma

Back 358

patient presents with chest pain, dyspnea, and effusion

tumor can directly invade the lung or have metastatic spread to hilar nodes, liver, or other distant organs

pulmonary asbestosis is only present in 20% of cases

1YS=50%, few ppl survive >2yrs

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besides the pulmonary pleura, where can mesothelioma present?

Back 359

peritoneum
- still related to asbestos exposure
- intestinal involvement can lead to intestinal obstruction and death

pt presents with inanition, defined as:
- lack of mental or spiritual vigor and enthusiasm
- exhaustion caused by lack of nourishment