Pathology: Lung

Interstitial Disease................................................................................................................................................................... 2
COPD ....................................................................................................................................................................................... 7
Pulmonary Vascular Disease ................................................................................................................................................. 12
Pulmonary Neoplasia ............................................................................................................................................................ 16
Lung Infections ...................................................................................................................................................................... 22
Lung Development / Pediatric Lung Disease ........................................................................................................................ 29

1
 Interstitial Disease
Similar findings –combine clinical / path / radiology / etc for Dx
 Open lung biopsy more helpful Diffuse interstitial lung diseases
Interstitium: note that it supports the capillaries! Chronic
 Type II cells make surfactant, type I are large flat squamous cells  Chronic inflammatory infiltrates ± lung
fibrosis (IPF, collagen vascular
diseases)
 Granulomatus disorders
 Dusts (EAA / pneumoconiosis)
Acute
 Diffuse alveolar damage (DAD)
 Acute interstitial pneumonia (idiopathic)

Idiopathic Pulmonary Fibrosis (IPF)

Chronic interstitial pneumonitis: chronic inflammation in pulmonary interstitium; relatively nonspecific lesion (lots of causes)

Idiopathic pulmonary fibrosis: subset of idiopathic interstitial pneumonias

 Chronic inflammatory & fibrotic lesion

o Infiltrate: lymphocytes & plasma cells (± eos & PMNs)
o Fibrotic: ranges from fibroblast foci (acute damage / repair) to well formed collagen scars
 Interalveolar septa most prominently involved
 Lower lobes and subpleural areas most affected

Other characteristic findings

 Patchwork pattern: variability in degree of inflammation & fibrosis from area to area
 Temporal heterogeneity (some acute lesions, some late lesions)
 Fibroblast foci
 Honeycomb change (remodeling)
o Can see in almost any interstitial disorder; can’t make IPF Dx from Bx showing only honeycomb change
o Implies large cystic restructured areas of lung with diffuse fibrosis in between

UIP (usual interstitial pneumonitis): these histologic patterns (path correlate of IPF)
 Can also see in RA & other collagen vascular diseases (same findings; need to separate clinically / lab info / etc)
 Drug reactions can mimic IPF findings too

Pathogenesis of IPF
 Repeated stimuli  sequential lung healing aberrant wound healing  fibrosis
 See temporal heterogenetity in lesions (some young fibroblast foci, others well healed scars)

2
 IPF: Path Findings

L to R: CXR, CT, gross, wedge biopsy. Note small lungs with honeycombing in lower lobes / subpleural areas

Interstitial widening, F: fibroblast foci (recent injury) Remodeling of walls (L)  honeycombing (R) (now have no
chronic inflammation, I: interstitial inflammation (PCs, capillaries), ↓compliance, bronchiolar-type epithelium mucus
fibrosis lymphocytes) production & congestion.

Left:
F: fibroblast foci (more recent)
C: collagen (pinker, older)

Non-specific Interstitial Pneumonitis (NSIP)

 Diffuse & uniform chronic interstitial inflammation ± fibrosis
o Note from right: diffuse pattern without accentuation
o Cellular or fibrotic variants
o No subpleural accentuation; fibroblast foci not required
o no architectural distortion, no honeycomb change

 Commonly associated with:

o Collagen vascular disorders
o Hypersensitivity pneumonitis (e.g. EAA)
o Drug reactions
o Other slowly resolving lung injury

3
 Pneumoconiosis
ILD related to inhaled inorganic dust (asbestos, silica, etc.)
 Specific reactions correspond to certain irritants

Dusts can be fibrogenic (aspestos, silica, etc.) or inert (coal dust, iron – siderosis)
 Inert dusts generally just give you an abnormal CXR but aren’t clinically a problem
 Can also have mixed exposure (modified response, not like any single component)

Silica
 CXR: Large silicotic
nodules
 Dense, hyaline pleural
nodules ± pigmented
dust
Silicosis
Asbestos
 CXR: Calcified pleural plaques & interstitial thickening
 Similar to UIP at large view
 Asbestos fibers (DUMBELL SHAPED ferruginous bodies)
o Characteristic, can be in Mϕ

Siderosis (inhaled iron)

 CXR: Hazy but PFT ok
 Iron in Mϕ, interlobular septae

Asbestosis

Siderosis (iron)

Extrinsic Allergic Alveolitis (EAA)

A.k.a. Hypersensitivity Lung Disease
 Limited to the lung (vs. sarcoidosis)
 Reaction to inhaled organic dusts – many named for exposure (Farmer’s lung, etc)
o Molds, animal antigens, thermophiles, etc.

Granulomas: large & LESS WELL FORMED than sarcoidosis

 See poorly-formed granulomas, think inhaled hypersensitivity

Make sure to do AFB stain & fungal workup if you see granulomas!

4
 Sarcoid
Another ILD with granulomas
Multisystem disease: related to T-lymphocyte dysfunction

Granulomas: MORE WELL FORMED (“hard” or “naked”)

 RANDOMLY DISTRIBUTED (across all parts of lung)
 Primarily formed by histiocytes
 Can be found in wall of small airways (transbronchial Bx useful)
 No caseous necrosis (would think infection)
 Can persist  fibrotic change

CXR: Hilar adenopathy, interstitial lung dz, or both

Sarcoid EAA
Well formed Poorly formed
Granulomas
Randomly distributed Mostly in interalveolar septa
BOOP Rare Frequently present
Upper lobe Pachy infiltrates
CXR
Hilar adenopathy No adenopathy
Disease Systemic Isolated to lung

Diffuse Alveolar Damage (DAD)

Histological correlate of Adult (Acute) Respiratory Distress Syndrome (ARDS)
 Causes: infectious agents (viruses), toxic inhalants, drugs (heroin OD), shock,
radiation, various others

 Pathogenesis: damage to alveolar epithelium / epithelium  acute exudative

stage  edema (interstitial, intra-alveolar) + hyaline membranes + thrombi

 Can resolve or lead to fibroblast ingrowth  organization  fibrosis

Pathological Features & Stages:

Acute exudative Proliferative Organization
 Interstitial
 Endothelial /  Fibroblast
inflammation
epithelial damage proliferation
 Type II pneumocyte
 Interstitial edema (in septa, within
proliferation
 Hyaline membranes alveolar lumen)
 Microthrombi

Can resolve from any

of these stages (but
very rare if organizing)

5
 Hyaline membranes – pink, dead epithelial cells
CXR: Cloudy
(fibrin looks more beady). Interstitial widening too

Proliferative changes: type II

Gross: dense, collapsed lung
pneumocytes (type I dying)

Above: outcomes & events of ARDS

Left: Organization (vascularizing) with areas of fibrosis (F) – leads to an
ineffective epithelium for gas exchange
Acute Interstitial Pneumonia
 Diffuse alveolar damage with no known etiology
 “Hamman-Rich Syndrome”
 Pathophysiology
o Neutrophils (oxidants, proteases)?
o Mϕ (ILs, TNF, etc)?
o Depletion / inactivation of surfactant?
o O2 / mechanical ventilation?

6
 COPD

Normal Airway Review

Bronchi: 30% cartilage (bronchioles don’t have)
Airway structure review:
 15% mucus glands, 5% smooth mm  Bronchi  terminal bronchioles  resp
 Connective matrix (arteries / veins / lymphatics/ nerves) bronchioles
 8-24 divisions to reach alveoli
Picture: normal bronchus  Larger central airways = most resistance
 A: collagen should be loose  Total surface area ↑↑ with < 2mm airways
 B: pseudostratified ciliated columnar epithelium
 C: Cartilage (bronchi only)
 D: Seromucinous glands (mucinous lighter; serous darker pink) –
secrete proteinaceous fluid

Epithelium Types
 Bronchi : ciliated pseudostratified columnar
 Bronchioles: flatter (more cuboidal)
 Alveoli: flat (pneumocytes: type I & II)

Terminal bronchioles:
 Lack cartilage
 Muscle layer about 20% of thickness
 Important in disease processes

Gas exchange: pass through:

endothelium, connective tissue, epithelium

Disorders of Airflow Obstruction (COPD Spectrum) – summary table

Clinical Term Anatomic Site Major Pathologic Changes Etiology Signs/Symptoms
Mucous gland hyperplasia, Tobacco smoke, air Cough, sputum
Chronic bronchitis Bronchus
hypersecretion pollutants production
Persistent or severe Cough, purulent sputum,
Bronchiectasis Bronchus Airway dilation and scarring
infections fever
Smooth muscle hyperplasia, excess Immunologic or Episodic wheezing, cough,
Asthma Bronchus
mucus, inflammation undefined causes dyspnea
Airspace enlargement; wall
Emphysema Acinus Tobacco smoke Dyspnea
destruction
Small airway Tobacco smoke, air
disease/ Bronchiole Inflammatory scarring/obliteration pollutants, Cough, dyspnea
bronchiolitis miscellaneous

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 Asthma
Pathophysiology
 Extrinsic: type I hypersensitivity
st
o 1 exposure: Sensitization
(Ag recognized by T-cell, etc)
nd
o 2 exposure: mast cells / hypersensitivity
response (mucus secretion, ↑ inflammation, muscle
contraction  bronchoconstriction)
 Intrinsic: non-immune (viral infections, drugs, inhaled
irritants, stress, exercise)
o Mast-cell independent (eos have big role)
o Same kinds of downstream reactions

Path Features:
 Intraluminal secretions:
plasma, inflammatory cells, desquamated epithelial cells.
 Airway epithelial desquamation
 Goblet cell hyperplasia
o Can result in mucus plug
 Airway inflammation: lymphocytes (CD4 mostly) / eosinophils
o Charcot-Leyden crystals: pink; from eos’ products
 “Hyalinized basement membrane: collagen fibrils”.

It would be weird to see this stuff in practice (Bx of asthma? Yeah right.)

Charcot-Leyden Crystals Goblet / Mucus cell

Mucus plug
(may be imaginary) hyperplasia

8
 COPD
Cigarette smoking is the big deal, ↑↑ COPD in females recently
Chronic obstructive pulmonary disease: disease state characterized by presence of:
 chronic bronchitis or emphysema
 with airflow obstruction, which may be accompanied by airway hyperreactivity
 may be partially reversible but is relatively fixed

COPD: Chronic Bronchitis

 Chronic cough & mucus production ± airflow obstruction

BRONCHIAL INFLAMMATION: lymphocytes, mϕ, PMNs

 Hypertrophy of glands; goblet cells
 Thick BM
 Inflammation  remodeling  airflow limitation (?)

Chronic Bronchitis

Left and above:

note bronchial involvement with
gland hypertrophy Bronchial inflammation

Emphysema
Emphysema: Abnormal and permanent enlargement of
 airspaces distal to terminal bronchioles
 accompanied by destruction of their walls
 without obvious fibrosis

Centriacinar emphysema: respiratory bronchiole

Panacinar emphysema: alveolus & duct

Morphologic types
of emphysema
 Centriacinar (centrilobular)
 Panacinar (panlobular)
 Paraseptal (distal acinar)
 Irregular
(very commonly overlap)

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 Centriacinar Emphysema
Features
 Respiratory bronchiole affected
 Normal alveoli
 Upper lobes ( worst in apical segments)
 Black pigment in wall commonly
 Can involve alveoli if severe
(DDx from panacinar may be impossible)
 Predominantly in smokers (also coal workers)

Subpleural bullae common (can rupture  pneumothorax)

Upper lobes 
anthracotic
pigment
deposited in
scarred
terminal
bronchioles

Center of acinus (respiratory bronchiole)

affected; spared rim around outside
Inflammation around bronchioles

 Bleb: separation of pleural layers

 Bullae: subpleural destruction of lung tissue

Above: subpleural bullae common

(gross on left, big air space on LM on right).

Panacinar Emphysema

 Entire respiratory lobule affected (terminal bronchiole to alveoli)

o See picture: no sparing of rim, bigger spaces than centriacinar
 Lower zone & anterior margins (worst at bases)
 Associated with alpha-1 antitrypsin deficiency

Paraseptal emphysema
 Distal portion of acini affected
 Adjacent to pleura, lobular septae, at margins of lobules
 Also seen adjacent to fibrosis, scarring, atelectasis
 Upper half of lung = more severe
 Multiple confluent airspaces
o See picture: larger, cyst-like spaces
 Most likely frequent cause of spontaneous pneumothorax in young adults
o (usually tall thin males)

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 Irregular emphysema
 Acinus irregularly involved
 Usually associated with parenchymal scarring
 Very common; often asymptomatic

Pathogenesis of Emphysema
• Alveolar inflammation: ↑↑ PMNS & Mϕ
• Protease/antiprotease imbalance
– Neutrophil: source of elastase
– Macrophage: source of metalloprotease
– Loss of antiproteolytic proteins:
alpha1 antitrypsin deficiency
• Alveolar cell apoptosis
• Oxidative stress: interaction with others

He had a summary table at the end of his notes; there were so many corrections made verbally in lecture that it seemed useless.

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 Pulmonary Vascular Disease
Pulmonary & Bronchial Arteries: Dual Blood Supply to Lungs
Pulmonary Arteries: carrying deoxygenated blood from heart to lungs
In order from proximal (near hilum) to distal (alveoli):
Type of
Size Description Pictures
artery

6 mm – 500 microns Similar to main pulmonary arteries, aorta

Elastic (Largest)
Left: normal stain; Right: elastic stain (see elastic fibers)

Similar to systemic muscular arteries but:

 double (internal & external) elastic lamina

500-70 microns Only pulmonary vessels that can regulate blood flow
Muscular (Medium) via vasoconstriction

Left: M = muscular media layer.

Right: I = internal elastic lamina, E = external elastic lamina

Medial (muscular) layer thins out / disappears

 (around 70 microns)
Non- <70 microns
(Smallest) Acquire pericyte layer (important endothelial functions)
Muscular
M: muscular medial still present; N: more distally, non-
muscular artery (muscular layer disappears)

Bronchial Arteries: systemic muscular arteries, arise from aorta

 Enter lung either by accompanying airways or coursing over pleural surface (enter peripherally)
 Anastamose with pulmonary arterial system
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 Pulmonary Hypertension
Defined hemodynamically (not by clinical Sx or pathology): Definition of Pulmonary Hypertension
Mean PPA > 25 mm Hg (rest) or >30 mm Hg (exercise)
Why is it bad?
 Need low perfusion pressure or fluid pushed out into interstitium  Mild-moderate: 25-45 mm Hg
(pulmonary edema)  Severe: > 45 mm Hg (systemic pressures)
 RIGHT HEART FAILURE most common cause of death in pts with severe PAH

Path findings
 Pulmonary vascular remodeling (intima, media, adventitia changed) – depends on severity & size of artery

INTIMAL THICKENING – looks like atherosclerosis

Large  Foamy Mϕ accumulate in intima  calcification
pulmonary arteries  Myofibroblasts surround Mϕ

(>500 microns, elastic) Atherosclerotic lesions:

 correlate with long term severe ↑ PPA but not used to Dx (not very specific)

Either smooth-muscle based or endothelial-cell based M: marked enlargement of muscular

media (should be ≈ 10% diameter)
Smooth-muscle-cell based remodeling
 present irrespective of PPA level, also in normal
individuals or pre-HTN!
Medium  In both mild and severe PAH
pulmonary arteries
Arrow: plexiform lesion (at branch
(500-70 microns, point; can see plexus of little vessels
muscular) – endothelial proliferation causes
Plexiform lesion: a type of endothelial cell growth
this.
 Often at branch points from larger arteries
 In SEVERE PAH ONLY (NEVER NORMAL or mild PAH)
May see vascular dilation or
 PATHOGNOMONIC FOR SEVERE PAH angiomatoid lesions nearby

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 Classification of Pulmonary HTN
1. Pulmonary Arterial Hypertension
a. Idiopathic (think young women 3:1 vs men) Mild/moderate PAH Severe PAH
b. Familial  COPD  Idiopathic
c. Associated with other diseases (same vascular morphology in the lung as idiopathic PAH:  ILD  Collagen vascular Dz
congenital systemic  pulmonary shunts, HIV, collagen vascular disease, liver disease and others)  Sleep apnea  HIV infection
2. Pulmonary hypertension with left heart disease  Congenital heart
3. Pulmonary hypertension associated with primary lung disease and/or hypoxemia malformation (LR shunt)
4. Pulmonary hypertension due to chronic thrombotic and/or embolic disease  Sarcoidosis
5. Miscellaneous

Other Path Findings (chronic obstructive lung diseases, primary interstitial lung dz like IPF, etc.)
Disease processes Picture
This artery shows both medial
hypertrophy (M) and fibro-intimal
hyperplasia (F) with fibroblasts &
 Muscular hyperplasia myoblasts.
Vascular Anything that ↑ pressures
remodeling (remodeling is response)
 Fibrous intimal thickening Can see both, or just one

Emphysema: lose capillary bed with

destruction of parenchyma
 Emphysema
Capillary bed loss
 Interstitial lung disease

Arteries this far out (<70 microns)

aren’t supposed to have smooth
muscle!

Abnormal muscularization of COPD, Stained with smooth muscle actin

distal pulmonary arteries esp. chronic bronchitis immunostain

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 Pulmonary Emboli
Epidemiology: about 600k/yr, most from lower leg

PE usually doesn’t cause pulmonary infarction (dual blood supply; would need double infarct) but can if…
 ↓ LV function or CHF (not perfusing bronchial circulation)

Acute: e.g. saddle embolus:

 can dislodge from lower leg / right heart  stick in pulmonary artery branch point
 Complete occlusion  RH dysfunction  arrhythmia, sudden death

Chronic thromboemboli:
 Can lyse, be incorporated into intima, or become recanalized (restore blood flow)
 If multiple pulmonary arteries: superimposed pulmonary HTN  see vascular remodeling as above Saddle embolus wedged in PA branch point
o Need >80% arteries blocked
 Path findings
o Thickening of intima & lumen
o Fibrotic bridges in vascular lumen (organization of previous thrombi)

Emboli that aren’t thromboemboli

 IV drug use: can have emboli of matrix / “filler” used in prescription drugs
o Microcrystalline cellulose, etc.
 Carcinomatous emboli: can (rarely) be numerous enough to produce pulmonary HTN
 Amniotic fluid emboli in pregnancy

Re-canalized emboli: can see that new channels

IV drug use embolus: see foreign body giant cell reaction in muscular pulmonary arteries (left); have formed
with polarized light, see a crystalline reflective substance (filler from drug)

15
 Pulmonary Neoplasia
Notes on terminology: MORPHOLOGICAL VARIANTS OF LUNG CANCER
 Small cell vs non-small-cell-  Squamous cell carcinoma
lung-cancer: previously didn’t  Adenocarcinoma
distinguish between NSCLC  Small cell carcinoma
because treatment was the same;
 (pulmonary carcinoid)
now need to subtype
 Large cell lung cancer: probably Derived from airway epithelial cells
poorly differentiated squamous cell carcinoma or adenocarcinoma

Squamous Cell Carcinoma

Histology: squamous differentiation
 Moderate to poor differentiation MAJOR FEATURES
 Nests of cells, keratization / intracellular bridges  > 95% in smokers
 Large tumors: necrotic centers  Involve LARGE AIRWAYS
o Can use bronchoscopy to visualize & Bx
Cytology:  More centrally located
 Hyperchromatic nuclei
 Variable keratinization (depends on differentiation) in cytoplasm

Around central airways Nests of cells, keratinization, whorls, intracellular bridges

Also see squamous metaplasia in other airways (widespread tobacco smoke injury) 
 Carcinoma can develop from sites of in situ squamous carcinoma / dysplasia

Adenocarcinoma

Glandular carcinoma, more heterogeneous than squamous cell carcinoma

Histology:
 IRREGULAR gland formation
 +/- mucin secretion MAJOR FEATURES
 > 80% in smokers (non-smoker with
Cytology: lung cancer: think adenocarcinoma)
 Round / oval nuclei  Involve SMALLER AIRWAYS
o Use transthoracic needle biopsy
 Prominent nucleoli
 More peripherally located
 Less hyperchromasia than squamous cell

16
 Can’t differentiate grossly

Some have a papillary differentiation (see bottom right)

Glandular appearance

Bronchoalveolar Carcinoma
 “Lepidic” growth pattern – like butterflies on a tree
(malignant cells on alveoli) MAJOR FEATURES
 Can grow extensively through lungs (mimic pneumonia)  Variant of adenocarcinoma,
 If confined to small area/nodular: resect  Uncommon but only 50% in smokers
 Involve peripheral lung
 Can have focal BAC in adenoCa
 Malignant cells grow along alveolar
walls without invasion

Alveolar walls well preserved, less fibrous Malignant cells growing along
stroma / tissue reaction alveolar walls

Atypical Adenomatous Hyperplasia (AAH)

 Most often seen in adenocarcinoma
 Not really hyperplasia (term used incorrectly)
 8mm or less in peripheral lung, often multiple
 Like bronchoalveolar carcinoma but just smaller (size is only difference)

Controversy: is AAH pre-invasive precursor to adenocarcioma?

Yes
 Looks like BAC / BAC-like areas of
adenocarcinoma
 Molecular changes of adenocarcioma
 Seen in pts with adenocarcioma
No
 Frequency of recurrence no higher in
pts with AAH
 Limited follow up  no evidence of
progression to adenocarcinoma

No longitudinal data is convincing at this point

17
 Large Cell Carcinoma
Probably just adenocarcinomas or squamous cell carcinomas that
aren’t differentiated enough to allow histologic classification
MAJOR FEATURES
 Mostly in smokers
 ↓ LCC Dx with ↑ use of IHC
 Airways of all sizes / locations
Can have giant cell (large, bizarre cells) or neuroendocrine differentiation  LARGE, AGGRESSIVE tumors
 Signals poor prognosis if one of these variants

Huge tumors Poorly differentiated, larger cells Highly abnormal nuclei

Non-small-cell lung cancer

Applies to all of the above; use IHC now to subclassify because chemo protocols differ between these types

Small cell carcinoma of the lung

Histology & Cytology:
 Small cells, somewhat look like lymphocytes
MAJOR FEATURES
 ↓ cytoplasm with relatively large hyperchromatic nuclei  >95% in smokers
o “Salt / pepper” finely granulated chromatin  Large, central airways
 ↑ mitotic figures / apoptosis; large tumors  necrosis  Neuroendocrine differentiation
 Little stromal response  HIGHLY AGGRESSIVE

HIGHLY AGGRESSIVE  METASTASIZE WIDELY

 On diagnosis, assume that it’s already metastasized (non-resectable) even if small & no mets recognized

Smaller cells with “salt-pepper” type of chromatin (finely Can have COMBINED small cell / non-small-cell carcinoma
granulated); lots of mitoses (aggressive) Left: SCLC + adenocarcinoma; Right: SCLC + squamous
carcinoma

Small cell carcinoma might be epithelial in origin (combined small cell / NSCLC variants – differentiated differently?)
If combined SCLC / NSCLC: might only get one type on Bx!

18
 Carcinoid Tumors
 Usually central (involve airway)
 Presentation: bronchial obstruction
 NEUROENDOCRINE differentiation
 DOES NOT PROGRESS to small cell lung cancer (although may look similar – neuroendocrine differentiation)


Occluding bronchial lumen Small, round cells without many mitoses (not SCLC)
Organoid pattern: stroma + capillaries between ball-like tumor
cell collections: like in normal neuroendocrine organs (adrenal
medulla, parathyroids, etc.) – also neuroendocrine marker +

Atypical carcinoids: invasion & atypical features

 Can recur locally or metastasize
 Still DOESN’T PROGRESS to SCLC Atypical carcinoid

Patterns of Invasion & Metastasis

Lung cancer metastasizes…

 Directly to adjacent tissues (pleura & mediastium)

 Lymphatics: LN, brain, bone, liver, adrenals

 Hematogenous / aerogenous spread more rare

Staging
Clinical staging: assessment of radiographic studies
Pathological staging: examination of tissue

Important for predicting survival

 VERY POOR (both NSCLC + SCLC)
o Only 60% at 5 yrs for stage 1!
o Stage IV (distant met)  almost nobody at 2 yrs

19
 Molecular Stuff
 p53 mutation common in all variants (more aggressive)

Adenocarcinoma: generally have either EGFR or KRAS (not both)

 Epidermal Growth Factor Receptor (EGFR) mutations EGFR mutations

o inhibition helps shrink tumor (oncogene addiction)  Women, Asian descent, non-smokers
o Especially in adenocarcinomas with bronchoalveolar features
 Almost exclusively adenocarcinomas
o Can also be amplified (mostly squamous diff) but not good
 Response to EGFR inhibitors (Erlotinib)
clinical response to EGFR inhibition
o Erlotinib (EGFR inhibitor): response is good, but doesn’t correlate with improved survival

 KRAS: mutated in subset of adenocarcinomas; exclusive of EGFR mutations

o No response to EGFR inhibitors

Paraneoplastic syndromes in lung cancer

Lung cancer can present first with other systemic sx
 General: fever + cachexia
 Endocrine syndromes:
o SIADH
o ectopic ACTH
o hypercalcemia (PTH-like substances)
 Neurological paraneoplastic syndromes; Dermatomyositis
 CLUBBING (hypertrophic osteoarthropathy) – see picture
o Pathophysiology: not well understood; maybe growth factor related?

Detection
Sx: only in advanced stages of disease (metastasis / paraneoplastic syndromes)
 Primary cancers (cough / hemoptysis) = advanced too
 Means survival is down (worse stage IV vs I, although both are bad)

Early detection: detect it while treatable

 X-ray & sputum cytology: tried it, didn’t improve survival
 High res CT is all the rage now
o One uncontrolled study found good outcomes
o Mayo clinic looked at it vs before high-res CT: ↑ detection,↑ resection, but survival & advanced cases the same!
 Lessons:
o Can’t detect highly aggressive cancer in “window of opportunity” for Tx
o Treating indolent (non-aggressive) lung cancers doesn’t ↑ survival (and more risk from procedure!)
o May be overtreating some indolent cancers!

Diagnosis
Depends on location of tumor; anything you see on radiography needs to be confirmed with histology / cytology
 Sputum cytology Centrally located cancers
 Bronchial brushings (e.g. squamous cell, exfoliates a lot of cancer cells into airways, can get with sputum)
 Bronchial biopsy (if needed) (SCLC central too)
 Trans-thoracic needle biopsy / aspirate Peripherally-located cancers (e.g. adenocarcinoma)
 Open lung biopsy (if needed) that are inaccessible via bronchoscopy

20
 Cigarette Smoking and Lung Cancer
Smoking causes cancer (surgeon general – 1964; first reports in 50s)

Tobacco Master Settlement (1988)

Good Bad
 $246B to states  States rely on tobacco settlement funds
 ↑ warnings (can’t hurt companies too much)
 ↓ advertising  $11B in legal fees

The Changing Cigarette (or, why ↑adenocarcinoma and ↓ squamous cell carcinoma)

Change Supposed to In Reality End Result

↑ stems
↑ nitrates (NNK) – specific for adenocarcinoma in lung ↑ adenocarcinoma (↑ NNK)
and ribs
↓ smoke ↓ PAH (polycyclic aromatic hydrocarbons) from tar but ↓ squamous cell carcinoma (↓ PAH)
Filters (mainstream), smokers cover vent holes, puff more frequently, and ↑ exposure of peripheral lung & more
Trap tar increase puff volume to ↑ nicotine exposure to NNK (breathing deeper, etc)

NOW: ADENOCARCINOMA IS THE MOST COMMON LUNG CANCER IN BOTH SMOKERS AND NON-SMOKERS

Other causes of lung cancer

Etiologic agents Comments
Cause of lung cancer in occupationally exposed individuals; appears to be synergistic with
Asbestos
cigarette smoking
Demonstrated as cause in uranium miners, where it was shown to be synergistic with smoking.
Radiation
The role of low-dose radon exposure in homes is not well established.
Indoor smoke associated with lung cancer in China.
Air pollution
Severe urban air pollution may also increase incidence.
Genetic predispositions Only rare families show linkage that suggests a genetic predisposition
Arsenic/ chromium High exposure limited to few individuals

Mesothelioma
 >80 associated with ASBESTOS EXPOSURE
 Glandular or sarcomatous differentiation
 Pleural lesions (mesothelium) – see picture
 Poor prognosis
 2k pts / yr (vs 200k for conventional lung cancers)

Metastatic Carcinoma
 Lots of other cancers like to metastasize to the lungs
 Frequently MULTIPLE METASTATIC WELL-DEFINED NODULES
o (vs single & invasive for primary lung cancer)
 Pleural lymphatic spread common too

21
 Lung Infections
1/6 of all deaths in US every year! Why?
 Large surface of alveolar space exposed to contaminated air TYPES OF PNEUMONIAS
 Aspiration (nasopharyngeal flora)
 Effects of other disease on immune system Gross Classification (CXR)
 Lobar vs bronchopneumonia
Bacterial Pneumonia Etiological Classification (clinical)
Classification:  Community-acquired (CAP)
 Lobar & bronchopneumonia  Nosocomial (hospital-acq, HAP)
 CAP (community-acquired)  Aspiration pneumonia (bacterial & chemical)
 Pyogenic pneumonia Atypical pneumonia
 (uncommon bacteria & viruses)
Pathogens
Chronic pneumonia
 Strep or pneumococcus pneumoniae
 (fungi, uncommon bacteria – nocardia)
 Also staph, pseudomonas, gram neg bacteria

Clinical picture:
 Abrupt onset of fever, chills, productive mucopurulent cough, pleuritic chest pain.

Diagnosis: blood cultures

Acute Bronchopneumonia
 PMNs are key cells
 Not limited by line of demarcation (fissure)
between two lobes

Lobar pneumonia: limited by fissures Acute Bronchopneumonia

 Similar microscopically to broncopneumonia
4 morphological stages of lobar pneumonia
 vascular congestion and edema
1. Congestion
 heavy lungs, frothy material on compression
2. Red hepatization  exudate formed by polys; fibrin and clotted RBCs in alveolar spaces
(consolidation)  liver-like consistency
 RBCs break down; exudate remains
3. Gray hepatization
 gray-brown dry surface
 consolidated exudate enzymatically digested
4. Resolution
 debris resorbed, ingested, or coughed up; normal structure

Early pneumonia: fibrin Fluid, prominent Advanced organizing pneumonia: lung trying
PMNs, Mϕ cleaning up
exudation into alveolar capillaries, cells into to heal; like granulation tissue. Fibroblast foci
debris now
spaces alveolar spaces (lighter texture, lots of spindle-like fibroblasts)

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 The Pneumonia Syndromes
 Community Acquired Acute Pneumonia (bacterial)
 Chronic Pneumonias (mycobacteria, granulomatous)
 Community Acquired Atypical Pneumonia (viral)
 Necrotizing Pneumonias & Lung Abscess
 Nosocomial Pneumonias (bacterial)
 Pneumonia in the Immunocompromised Host
 Aspiration Pneumonia (bacterial & chemical)

Complications of bacterial pneumonia

 Abscess
 Empyema (pus / exudate in pleural space)
 Organization of exudate with fibrosis
 Bacteremia with dissemination of organisms to heart valves, brain, etc.
 Pleuritis
 Pleural effusion
Empyema
 Bronchopleural fistula (fibrin, pus exudate:
pleural surface of lung)
Viral / Atypical Pneumonias
A.k.a. Primary Atypical Pneumonia; more accurately interstitial pneumonitis
Clinical Course
Why atypical?  Variable, usually mild
 Lack of consolidation (alveolar exudate)  Fever, headaches, possible dry
cough
 Lack of sputum production
 Significant respiratory distress*
 Predisposes to bacterial infection
Acute febrile respiratory disease with patchy inflammatory changes in lung  Treat empirically
 Largely confined to septae & interstitium  Usually resolves without sequelae

Primary Atypical Pneumonias

Coryza (“cold”) Lots of nasal discharge & pharyngitis (various viruses)
Mycoplasma Most common cause (“walking pneumonia”)
 Children, young adults; epidemics in schools, military camps, prisons, hospitals, etc.
 Bad, persistent cough
Chlamydia #2 cause
Other Influenza A & B, RSV, adenoviruses
More on atypical pneumonias:
 Patients: early childhood, or immunocompromised pts of any age
 Pathogenesis: NO PUS
o Attach to resp epithelium  necrosis of cells / inflame response  interstitial inflammation (if extend to alveoli)
 Course: Resolve spontaneously ± erythromycin if mycoplasma or chlamydia
o Severe (rare): can  ARDS (50% fatal)
o Damaged epithelium  predisposition to 2° bacterial infection‼!
 Sputum: cleargreen/yellow, think bacterial superinfection
 Sx/findings: can present as URI (“common cold”) or more severe LRI
o Headache, fever, cough, patchy infiltrates on CXR
 Rx: mycoplasma & chlamydia w/ erythromycin or other abx
 Histopath: Intersitial pneumonia with mononuclear infiltrate (DAD if very severe)
Atypical Pneumonia: Path

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 Thickening of alveolar Interstitial pneumonia with RSV: characteristic giant cells
Interstitial Pneumonia.
wall; no PMNs diffuse alveolar damage:
MONOnuclear infiltrate:
HYALINE MEMBRANES form,
Mϕ & lymphocytes in interstitium
↓ gas exchange
(not PMNs)
(ARDS is correlate)

Severe Acute Respiratory Distress: SARS

March 2003, Guangdong province, China

Sx: Dry cough, malaise, myalgias, fever, chills
Course: 1/3 resolve, remainder  severe resp dz; 10% die
Cause: previously undiscovered coronavirus (unique: infects lower resp tract  spreads throughout body)
Transmission: civet  human, now humanhuman via resp secretions
Dx: PCR to detect virus, antibodies

Pathology: DIFFUSE ALVEOLAR DAMAGE with GIANT CELLS (resembles ARDS)

Aspiration Pneumonia
Patient: markedly debilitated (unconscious, stroke victims, alcoholics, repeated vomiting)
 Abnormal swallowing & gag reflex

Mixed chemical + bacterial pneumonia

 Gastric acid, enzymes  lung damage (edema + bleeding)
 Necrotizing: very serious!; Bacteria can grow
 Goes to dependent position (GRAVITY)
o Lower (upright) or Middle (laying down) right lobe
 R bronchus is straighter down
 LUNG ABCESSES common!
 Can see gastric contents or foreign body giant cell rxn (see picture)

Chronic Pneumonia
Think NOCARDIA: #1 for chronic pneumonia!

 Weakly staining Gram + rod-shaped bacteria;

forming partially acid-fast beaded branching filaments

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 Tuberculosis
M. tuberculosis is causative agent; chronic, communicable dz
 Slender, acid-fast rods (lots of lipids  resist decolorization) Granulomatous Infection DDx:
o Stains: carbol fuschin & decolorize with alcohol;  TB (+ atypical mycobacteria)
fluorescent (auramine-rhodamine) more sensitive  Fungal infections
 Drug resistance is big problem

Epidemiology: 1.7B infected, 1.8M deaths, 6% of all deaths worldwide!

Uncommon in US, 20x↑ in poor countries
↑ infection in costal SC; ↑ in immigrants (Hispanic/Asian countries  40% new cases) ↑ with AIDS (now↓ in US)
Transmission: Inhalation of infected droplets (cough/sneeze) or exposure to resp secretions (reservoir: humans with active Dz)
At-risk: debilitation, immunosuppression, elderly
Geography: poverty / crowding / chronic illness PPD (purified protein derivative)
 Intradermal injection
 Rxn peaks at 48-72 hrs
Course: having “TB” doesn’t mean disease necessarily  Measure size (not redness) of induration
 >5mm = positive
 Primary infection: causes minor reaction
(cell-mediated hypersensitivity to TB Ag in pt)
o Delayed hypersensitivity develops
(detect with PPD 2-4 weeks after infection)
 15M positive in US
(5-10% US pop; 23K new active cases-yr – after
o Well formed granulomas, caseation necrosis, PPD + conversion, 3-4% acquire active TB in 1 yr, <15%
thereafter)
 Reinfection or Reactivation of existing, walled-off infection 
serious disease False Negative PPD: IMMUNOSUPPRESSION
(anything that causes anergy)

Path: Necrotizing granulomatous caseating response (ddx vs fungal)

Miliary TB (multiple Left: Necrotizing caseating granuloma Acid-Fast

caseating granulomas) Right: histiocytes, multinucleated (Langerhan’s) giant cells

TB: Course

Immunity: expose naïve immuncompetent person to TB

 Mediated by T-cells, hypersensitivity and resistance develop in parallel
 Hypersensitivity: allows fast mobilization of rxn but ↑ tissue necrosis
o If hypersensitivity ↓, means resistance has faded
o No necrotizing granulomas in HIV!

First infection: 1° TB
 Inhalation  lung  proliferates in mid-lung subpleural location
 Taken up by pulmonary alveolar Mϕ
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 o Some Mϕ degrade / present mycobacterium  hypersensitivity
o In others, phagolysosome inhibition  survives & proliferates in Mϕ  regional lymph nodes
 < 3wks: unchecked proliferation in Mϕ & airspaces (bacteremia!)
Ghon lesion:
 3wks post infection: well formed granulomas, caseation necrosis, PPD + initial focus of 1° infection
o Mϕ present to T-cells  TH1  secrete IFN-γ  activate Mϕ  NOS, TNF
 ROS (kill bacteria/ cells)  caseous necrosis, tissue destruction Ghon complex:
 TNFα  monocyte recruitment  diff to Mϕ  granulomas Ghon lesion + lymph node

Implications of 1° TB
 Hypersensitivity, ↑ resistance; can harbor viable bacteria (later reactivation)
 Can progress without interruption (progressive 1° TB)
o Immunocompromised (esp HIV+, certain racial groups)
o Can’t mount cell-mediated response
o Can resemble acute bacterial pneumonia: (consolidation, pleural effusion,
hilar adeopathy)
o Lymphohematogenous dissemination: rare & bad
 TB meningitis, miliary TB, death possible

Reactivation (2° TB)

 From previously sensitized host (5% 1° infection  2°, decades later)
 Can be from reinfection too (↓ immune, ↑ inoculum)
 Location: APEX or APICES of upper lobes (↑ O2 tension)
 Clinical: Cough, malaise, afternoon fever, night sweats, weight loss, anemia, fatigue
o Can cough up organisms, spread disease; 25% mortality if untreated
 Immune system is all jacked up & ready to go: big destruction of tissue

Manifestations & complications of 2° TB

 Tissue necrosis (lots of granulomas ± cavities)
 Miliary TB: erode into bloodstream; granulomas in many organs
 Hemoptysis: erode into airways
 Bronchopleural fistula: subpleural cavity ruptures into pleural space
o Empyema, pneumothorax can result
 Intestinal TB: from swallowing bacilli

Mycobacteria other than TB

M. bovis (unpasteurized milk: oropharyngeal, GI tract infections)
M. avium-intracellularae (MAI), often in AIDS
 Most common atypical mycobacteria
M. leprae, others; M. bovis & M. TB hominis are obligate aerobes

Common features:
 Immunocompromised pts
(AIDS, cancer, BMT)
 Poorly formed granulomas, fibrosis

Poorly formed granulomas MAI overwhelming Mϕ

(immunocompromised pts) 26
 Fungal Pneumonia
 Mostly inhaled  Necrotizing granulomatous inflammation (like TB)
 Cell-mediated immunity  Stain: GMS or D-PAS
Fungal Pathogen Features Pictures
Pt: chronic dz / immunocompromised

Invasive, saphrophytic, allergic

 Saphrophytic: feed off dead stuff
 why they can form fungal balls!
Aspergillus
Cx usually negative (need Bx)

Hemmorhagic infarction with sparse inflammatory infiltrate Aspergillus infection with Aspergillus ball 45° branching septate hyphae
Hyphae: invade blood vessels & alveolar septae infarction

See vegetative forms (hyphae+ pseudohyphae + yeast)

Candida
 means it’s not a contaminant!

Yeast, Hyphae, and Pseudohyphae

Southeast US (caves in Mississippi Valley)

 caseating, necrotizing granulomas
Histoplasma
Tiny organisms multiply in Mϕ (see pic)

Southwest US
Coccidiomycosis
Forms spherules (see pic)

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 Has a MUCOID CAPSULE
 shows up as empty space on normal stains
 can stain with special stains
Cryptococcus
Important in AIDS pts

Variable sizes

Double-walled appearance
Blastomycosis
+ acute inflammation

Pneumocystis Pneumonia

Pathogenesis:
 Hypoxia, restrictive defect
 Reproduces in association with Type I pneumocytes
 Active disease: lungs only
o trophozoite feeds  enlarges  transforms to cyst form
o Cyst ruptures, new trophozoites released, attached to alveolar lining cells

Pathology: Interstitial pneumonitis with intra-alveolar exudate

 Heavy firm lung (can cause DAD)
 Organisms: look like “CONTACT LENSES” on silver stain

Clinical Presentation:
 Can have minimal symptoms or fever, dyspnea, dry cough
 Can progress to respiratory failure (alveolar filling on CXR)

Dx: BAL, tranbronchial bx, IF, PCR

Formerly a major problem / often fatal in AIDS pts

 Now use prophylactic aerosolized pentamidine to prevent (other cases not so bad)

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 Lung Development / Pediatric Lung Disease
Lung Development
Lung: foregut derivative
Week Name What happens
th
26 day Lung appears: bud from caudal end of laryngeotracheal sulcus
0-5 Embryonic period Lung buds form lobar bronchi, major segmental branches
5-16 Pseudoglandular period Bronchial branching continues, cartilage develops
20 Surfactant production starts in type II pneumocytes
24-26 Surfactant sufficient to provide lung stability (ABCA3 produced, etc)
25 Thin air-blood barrier formed; theoretically can maintain respiration
26 - term Terminal Sac / “ Alveolar” period Shallow distal airspaces develop

Birth – 4 years Alveoli continue to ↑ in number

4-8 yrs Alveoli ↑ in size as chest wall grows (also ↑ number)

Three Laws of Lung Development

1. The bronchial tree is developed by the 16th week of
intrauterine life
2. Alveoli develop after birth
a. They increase in number until 8yo
b. They increase in size after 8yo until chest wall stops
growing
3. The development of pre-acinar arteries corresponds with
the development of airways

Fetal lung in glandular stage; lobes established already

Left: Glandular structures (arrowhead; will eventually connect to trachea) surrounded by thoracic mesenchyme (arrow).
Center & Right (LM & EM): close up; see all glycogen (arrow) but few organelles in glandular cells = haven’t differentiated yet

th
After 16 week: bronchial tree has developed Later: closer to term. Alveoli have subdivided over &
Couldn’t breathe yet over, connect to airways. Blood vessels from
(airways=arrows, airspaces=arrowheads are separate) mesenchyme have invaded alveolar walls

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 Surfactant
 Made by type II pneumocytes (produced, stored in lamellar bodies, secreted)
 ABCA3 protein involved in transport of material into LB
 Note that capillaries really wander back and forth across septae (not in middle) – from one side to other

LB secreted (phospholipids,
SEM from inside capillary TEM of alveolar septa; note capillary Lamellar bodies in type II
etc)  ↓ surface tension in
Arrow : type II pneumocyte wandering back and forth between pneumocytes
lung!
Arrowheads: capillaries adjacent alveoli

Why surfactant?
 There’s an air liquid interface (starling forces  leak out liquid), so 
 alveoli want to collapse

LaPlace’s Law
 The smaller an alveolus gets, the smaller it wants to be
 Alveolar stability due to tissue forces (elasticity – tethering) and alveolar lining layer
 Surfactant especially important in newborns
o 2/3 of alveolar stability provided by surfactant in newborns, ↓ in adults

What happens at birth?

Lung isn’t “collapsed” in utero: filled with fluid
 Intrauterine “respirations” keep amniotic / pleural fluid in contact
o (check amniocentisis to see lethicin levels  assess lung maturity!)
 At birth: empty fluid & fill with air
o ↑ RV with subsequent breaths (need surface tension ↓ via surfactant)

Transient tachypnea of newborn

 Retain fluid (don’t expel at birth) – cloudy CXR
 Gone by the enxt day

Respiratory distress in the Newborn

Idiopathic Respiratory Distress Syndrome is #1 for morbidity and mortality
 Also infection, CV/CNS disorders, etc – not just ARDS (bigger DDx)

For: newborn respiratory distress syndrome

Think: premature vs term? (IRDS vs meconium aspiration)

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 Idiopathic Respiratory Distress Syndrome
A.k.a. “hyaline membrane disease” (older name; infections / other causes of alveolar damage can also produce path findings)

Basic cause: deficiency of effective pulmonary surfactant  lung instability

 Immaturity (failure of production), failure of release, abnormal structure / function of surfactant, or combo
 Not really idiopathic!

Infants at risk for IRDS

 Premature infants  Second born of twins
(appropriate size/wt for gestational age) (maybe not paying attention during delivery?)
 Males > Females  Genetically determined disorders of surfactant system
 Whites > Blacks o Surfactant associated proteins
 History of previously affected premature o ABCA3 mutations / inactivity
 C-section < 38 wks with mother not in labor (transport of material into lamellar bodies – LBs are
 Infants of diabetic mothers weird shapes, etc.)
Lack of stress may be important- stress in mother  ↑ steroids, etc.

Path findings:
 Abnormal pattern of lack of expansion in lung
 Distal airspaces collapsed
 Distal airways dilated & lined with hyaline membranes (eosinophilic)
o Looks like DAD in ARDS! From cellular debris from alveolar lining
 Septal lymphatics dilated ± focal hemorrhage, edema

CXR: Ground glass appearance with air bronchograms

Complications:
 Development of PDA (reopen / fail to close)
 Bronchopulmonary dysplasia
 Interstitial emphysema (pulmonary alveolar air) & sequelae

Treatment of IRDS:
 Artificial surfactant; Give O2 + mechanical ventilation

Lung: all collapsed, looks like liver IRDS: most of lung collapsed with hyaline membranes (like DAD + collapse)

Alveolar ducts are main damage site Genetic surfactant protein deficiency
(rest is collapsed) Lots of proteinaceous material / Mϕ
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Bronchopulmonary Dysplasia – complication of treatment for IRDS
All you need to know from this part: bronchopulmonary dysplasia is a complication of treatment for IRDS

“Old” BPD: 28-32 wks gestation, complication of RDS & “New” BPD: <28wks, may be complication of RDS treated
treatment (high O2, vigorous +-pressure ventilation) with surfactant (or premature birth)
 Structural damage to airspaces, airways w/ fibrosis  Development / growth abnormalities in lung:
↓ alveoli, simplified alveoli

“old type”BPD with interstitial fibrosis “New type” BPD with collapsed areas, big open
areas, simplified alveoli

Pulmonary Interstitial Air

A.k.a. “pulmonary interstitial emphysema”
E.g.: Infants with IRDS ± BPD
 Air gets out of airspaces into interstitium
 Lung can pop  pneumothorax if air dissects out the whole way to edge of lung
o Pneumothorax: see pic to right

Not every infant with pulmonary interstitial air has IRDS

 Can have cystic congenital defects, etc, or with meconium aspiration syndrome
 pulmonary interstitial air may be more common than recognized but resolves on own
o 15% infants have a small
pneumothorax

Path findings:
 Cystic spaces around
bronchovascular bundles & septae of
lung (see pictures)
o Can misinterpret as “cystic
malformation”

AIR can produce a GIANT CELL REACTION!

 Don’t assume it’s a virus!

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 Meconium Aspiration Syndrome
Meconium = fetal poop (green  bile formation)

Meconium Aspiration Syndrome

 Stress of childbirth  big respiratory intake burst  babies tend to inhale meconium
 Tends to happen in mature or post-mature (not premature) – more vigorous respiratory intake movements

Findings
 Green stained placenta
 Meconium in larynx
 Patchy infiltration on CXR (like aspiration + pneumonia)
 Mucus & squamous cells in bronchioles & other small
airways, etc. on path
o Mucus is key (squamous cells in any
cause of newborn respiratory death)

Mechanism:
 Mucus blocks bronchioles like ball valve
air trapping 
 Pressure builds up, can dissect out of alveolus,
get pulmonary interstitial air

Perinatal Pneumonia
CLASSIFICATION OF PERINATAL PNEUMONIA
Transplacental  Part of a systemic congenital infection (usually maternal origin)
 Present at birth
Intrauterine  Aspiration pneumonia (infected amniotic fluid)
Aspiration

 From organisms in maternal vagina

 Signs in 1st wk of life
Acquired during birth  Maternal vaginal infection usually (esp poor prenatal care)
 GBS can be rapidly fatal if untreated
 Signs in 1st month of life
Acquired after birth
 Organisms from environment (staph, pseudomonas, serratia)

Group B Strep is a big problem in neonates!

 Check pregnant mothers for colonization

 Toxin causes diffuse alveolar damage!

o See hyaline membranes with

blue color (organisms!) CXR: patchy infiltrate (here like PMNs in alveolar spaces
bronchopneumonia)
o Pleural effusions too (not
common in normal DAD)

Group B Strep: GBS: HYALINE MEMBRANES with GPC (right)

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see pleural effusion here (GBS in setting of pleural effusion)
 Cystic Fibrosis
Autosomal recessive genetic disorder affecting multiple organ systems with protean manifestations

 CFTR: cystic fibrosis transmembrane conductance regulator (chr 7)

 Abnormal secretions  bacteria  damage, etc. (See chart)

 Mucociliary escalator messed up (abnormally hydrated mucus)

Causes of death: recurrent pulmonary infection, resp failure, cor pulmonale

 Many extrapulmonary features too
Earlier Later
Mucoid, alginate-producing pseudomonas mutants arise (harder to eradicate)
Mucus plugging of tracheobronchial glands
Burkholderia & atypical mycobacteria too
 Obstructs bronchi / bronchioles
 Infection follows  recurrent bronchitis,
Recurring bronchopneumonia  bronchiectasis
bronciolitis, pneumonia
 Parenchymal damage from bronchopneumonia 
scarring  retraction  dilate bronchi
Organisms: eventually can permanently colonize
 S. aureus
Lower resp tract problems:
 H. flu (less now with vax)
 Fibrosis around small airways
 Pseudomonas
 Interstitial chronic inflammation

Young CF pt: bronchopneumonia Older CF pt: accumulations of mucus, Bronchiectasis (B) – airways too big,
scarring, bronchiectasis too far out in lung. F = fibrosis too

Right:
Left: Pseudomonas
more bronchiectasis making a biofilm
in CF patient; clogged in abnormal
with purulent debris secretions (hard
to eradicate)

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