CHAPTER 15
THE LUNG FOREGUT CYSTS
THE RESPIRATORY SYSTEM
- Exchange gases between inspired air & blood.
- outgrowth from the Foregut Ventral Wall.
- Trachea develops 2 Lung Buds.
o Right Lung Bud = 3 Lobar Bronchi
o Left Lung Bud = 2 Lobar Bronchi
- Right Main Stem Bronchus is more vertical &
directly in line with Trachea ! more susceptible
to aspirated foreign materials
- Double Arterial Supply (Pulmonary & Bronchial
Arteries) to Lungs.
- Bronchioles = progressive Bronchial branching;
lacks cartilage & submucosal glands.
- Terminal Bronchioles = further branching of
Bronchioles; < 2mm
- Acinus = part of Lung distal to the Terminal
Bronchiole; 7mm, spherical; composed of
Respiratory Bronchioles, Alveolar Ducts, &
Alveolar Sacs ! Alveoli = site of gas exchange
- Pulmonary Lobule = 3-5 Terminal Bronchioles
important in distinguishing major forms of
Emphysema.
- Lined by Pseudostratified, Tall, Columnar
Ciliated Epithelial Cells (except the Vocal Cords
= Stratified Squamous).
- Mucosa has Neuroendocrine Cells secreting
Serotonin, Calcitonin, & Gastrin-Releasing
Peptide (Bombesin).
- Goblet Cells & Submucosal Glands @ Trachea &
Bronchi.
- Pores of Kohn = perforates the Alveolar Walls;
permit bacterial & exudate passage between
adjacent Alveoli.
Microscopic Components of the Alveolar Wall/Septa
Capillary Endothelium
Basement Membrane & Surrounding Interstitial
Tissue = fused in thin portions; separated by the
Pulmonary Interstitium in thick portions.
Alveolar Epithelium
o Type I Pneumocytes = flattened & plate-
like; 95%
o Type II Pneumocytes = rounded;
synthesizes Surfactant in Osmiophilic
Lamellar Bodies; involved in Alveolar
Epithelial repair via giving rise to Type I
Cells.
Alveolar Macrophages
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CONGENITAL ANOMALIES
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PULMONARY HYPOPLASIA/AGENESIS
- defective development of both Lungs !
decreased weight, volume, & Acini
disproportional to body weight & gestational age.
- r/t Lung compression or impeded Lung expansion
in utero (e.g. Congenital Diaphragmatic Hernia,
Oligohydramnios).
- abnormal detachment of Primitive Foregut in the
Hilum/Middle Mediastinum.
o Bronchogenic Cyst = rarely connected to
the Tracheobroncial Tree; lined by
Ciliated Pseudostratified Columnar
Epithelium with Squamous metaplasia in
areas of Inflammation; SURGICAL
RESECTION is curative.
o Esophageal Cyst
o Enteric Cyst
PULMONARY SEQUESTRATION
- presence of a discrete Lung tissue mass without
normal connection to the airway system.
- Blood supply arises from the Aorta or its
branches.
o Extralobar Sequestrations = external;
located in the Thorax/Mediastinum;
infants; r/t congenital anomalies
o Intralobar Sequestrations = internal;
older children; r/t recurrent localized
infection/bronchiectasis
Other Developmental Defects
a. Tracheal & Bronchial Anomalies (Atresia, Stenosis,
Tracheoesophageal Fistula)
b. Vascular Anomalies
c. Congenital Lobar Overinflation (Emphysema)
d. Congenital Pulmonary Airway Malformation
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ATELECTASIS (COLLAPSE)
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- incomplete expansion of the Lungs (Neonatal
Atelectasis) or collapse of previously inflated
Lungs (Acquired Atelectasis).
- Produces areas of airless Pulmonary Parenchyma.
- Reduces Oxygenation & predisposes to Infection.
- Collapsed Lung Parenchyma can be re-expanded
! REVERSIBLE (except Contraction Atelectasis)
RESORPTION (OBSTRUCTION) ATELECTASIS
- r/t complete airway obstruction ! resorption of
O2 trapped in dependent Alveoli without Blood
Flow impairment.
- Diminished Lung Volume ! Mediastinum shifts
TOWARD the Atelectatic Lung
- Caused by excessive secretions/exudates within
smaller Bronchi.
COMPRESSION ATELECTASIS
- Pleural Cavity is partially/completely filled by
Fluid Exudate, Tumor, Blood, or Air.
- Tension Pneumothorax = air pressure impinges
on & threatens Lung & Mediastinum function.
- Mediastinum shifts AWAY from the affected Lung.
CONTRACTION ATELECTASIS
- local/generalized Fibrotic changes in the Lung/
Pleura prevent full expansion.

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PULMONARY EDEMA
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HEMODYNAMIC/CARDIOGENIC PULMONARY EDEMA
- increased Hydrostatic Pressure (Left-Sided
Congestive Heart Failure)
- Heavy, wet Lungs; Dependent Edema = fluid
accumulates @ Basal Regions of Lower Lobes
(greater Hydrostatic Pressure)
- Engorged Alveolar Capillaries; Intra-Alveolar Pink
Precipitate
- Heart Failure Cells = Hemosiderin-Laden
Macrophages
- Brown Induration = Firm, Brown, Soggy Lungs r/t
fibrosis & thickening of Alveolar Walls
EDEMA CAUSED BY MICROVASCULAR INJURY
- injury to the Alveolar Septa Capillaries.
- Hydrostatic Pressure not elevated; Edema results
from primary injury to Vascular Endothelium or
damage to Alveolar Epithelial Cells.
o Fluid & CHON leak @ Interstitial Spaces !
Alveoli
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DIFFUSE ALVEOLAR DAMAGE
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ACUTE LUNG INJURY (ALI; NON-CARDIOGENIC
PULMONARY EDEMA)
- abrupt onset of Hypoxemia & Diffuse Pulmonary
Infiltrates in the absence of Cardiac Failure;
assoc. with underlying etiology (Sepsis).
- Acute Respiratory Distress Syndrome (ARDS) =
severe form; Lung injury is r/t imbalance of Pro-
Inflammatory & Anti-Inflammatory mediators.
o Nuclear Factor (NF) B shifts the balance
in favor of Pro-Inflammatory states.
- Acute Interstitial Pneumonia (AIP; Idiopathic
ALI-DAD)
o widespread ALI with a rapid progressive
cause & absence of etiologic association.
o 50 years old with no sex predilection
o URTI following an illness < 3 weeks
- Inflammation-associated increase in Pulmonary
Vascular Permeability & Epithelial & Endothelial
Cell Death
Morphology
- Acute Stage = Heavy, Firm, Red, & Boggy Lungs;
congestion, interstitial & inter-alveolar Edema,
Inflammation, Fibrin Deposition
- Waxy Hyaline Membranes lining the Alveolar Walls
- Type II Pneumocyte proliferation & Granulation
Tissue response
- Fibrotic Thickening of Alveolar Septa
- Superimposed Bronchopneumonia
Pathogenesis
- 2 Barriers of the Alveolar Capillary Membrane
(Microvascular Endothelium & Alveolar
Epithelium) is compromised in ARDS.
o High levels of Endothelial Injury &
Activation Markers
o Swelling, Vacuolization, Bleb Formation,
& Frank Necrosis
- Increased Vascular Permeability, Alveolar
Flooding, Loss of Diffusion Capacity, Surfactant
Abnormalities
- Microthrombi formation ! Ischemic Injury
- Hyaline Membranes r/t inspissation of CHON-rich
Edema Fluid entrapping debris of dead Alveolar
Epithelial Cells.
- 30 minutes after insult ! increased IL-8 synthesis
by Pulmonary Macrophages; IL-1 & TNF !
Endothelial Activation ! Pulmonary Microvascular
Sequestration & Neutrophil Activation (impt.
role)
o Neutrophils become stiff & less
deformable ! trapped in narrow
capillary beds ! release products
damaging the Alveolar Epithelium !
Inflammatory Cascade
- Dysregulation of Coagulation System
- Resolution requires Exudate resorption, removal
of Dead Cells, & replacement by new
endothelium & alveolar epithelial cells.
Clinical Course
- Profound Dyspnea & Tachypnea ! Increasing
Cyanosis & Hypoxemia, Respiratory Failure,
Diffuse Bilateral Infiltrates
o Hypoxemia becomes unresponsive to O2
Therapy due to Ventilation Perfusion
mismatching ! R. Acidosis
- Loss of Functional Surfactant ! Lungs become
Stiff
- Exudate & Diffuse Tissue Destruction does not
resolve ! Scarring
- Lungs are divided into Infiltrated, Consolidated,
or Collapsed Areas with areas of normal
compliance & ventilation ! V/P Mismatch &
Hypoxemia
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OBSTRUCTIVE PULMONARY (AIRWAY) DISEASES
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- Chronic Non-Infectious Diffuse Pulmonary
Disease
- increased resistance to airflow r/t partial/total
obstruction.
- Forced Expiration = Decreased Maximal Airflow
Rate
o Measured by Forced Expiratory Volume at
1 second
- Chronic Obstructive Pulmonary Disease (COPD)
o Emphysema (Acinar Level damage)
o Chronic Bronchitis (Bronchial Level
damage)
o r/t long-term heavy smoking
 - mild chronic inflammation throughout the
airways, parenchyma, & pulmonary vasculature
CHRONIC EMPHYSEMA
o increased Macrophages, CD8+ & CD4+ T-
BRONCHITIS
Lymphocytes, & Neutrophils ! activation
Age (years) 40-45 50-75 ! mediators ! Lung Damage
- Protease-Antiprotease Imbalance Hypothesis =
Dyspnea Mild/Late Severe/Early genetic deficiency of Antiprotease 1-Antitrypsin
Cough Early; Copious Late; Scanty compounded with smoking
Sputum Sputum o 1-Antitrypsin is encoded by Proteinase
Inhibitor (Pi) locus on chromosome 14,
Infections Common Occasional normally at the M Allele.
o Z Allele is associated with decreased 1-
Respiratory Repeated Terminal Antitrypsin levels.
Insufficiency
- Postules of Sx Panacinar Emphysema sequence
Cor Pulmonale Common Rare/Terminal (HIGH PROTEASE ACTIVITY):
o Neutrophils normally sequestered in
Airway Resistance " Normal/Slightly " peripheral capillaries ! gains access to
alveolar spaces
Elastic Recoil Normal Low o Stimulus increasing WBCs or release of
Chest Prominent Vessels Hyperinflation Proteases ! Proteolytic activity
Radiograph Large Heart Small Heart increased
o Low 1-Antitrypsin serym ! Elastic Tissue
Appearance BLUE BLOATER PINK PUFFER destruction is unchecked ! Emphysema
- Effects of Cigarette Smoking in developing
Emphysema:
EMPHYSEMA o Neutrophil & Macrophage accumulate in
- irreversible enlargement of airspaces distal to the the Alveoli r/t direct chemoattractant
Terminal Bronchioles with destruction of walls & effect of Nicotine & ROS effects
without obvious fibrosis. o Cellular Protease release ! Tissue
- Rx Fx = Heavy Cigarette Smoking, Women, African Damage
Americans o Enhanced Macrophage Elastase & Matrix
- Classified according to anatomic distribution Metalloproteinase activity
o Centriacinar (Centrilobular) Emphysema - Oxidant-Antioxidant Imbalance = ROS in smoke
Central/proximal acini are affected depletes antioxidant mechanisms ! inactivation
Distal alveoli are spared of native antiproteases ! Functional 1-
Emphysematous & normal airspaces Antitrypsin Deficiency
exist within the same acinus & - loss of alveolar wall elastic tissue ! reduced
lobule. radical traction ! respiratory bronchiolar
Lesions more common & severe in collapse during expiration ! Functional Airflow
upper lobes (Apical Segments) with Obstruction
black pigments - inflammation of Small Airways (Bronchioles
Bronchial & Bronchiolar Inflammation <2mm)
Heavy Smokers, Chronic Bronchitis o Goblet Cell Metaplasia with Mucus
o Panacinar (Panlobular) Emphysema Plugging
Uniformly enlarged Acini (Respiratory o Inflammatory Infiltration
Bronchiole to Terminal Blind Alveoli) o Bronchial Wall Thickening r/t Smooth
Common in Lower Zones & anterior Muscle Hypertrophy & Peribronchial
Lung margins (most severe at Bases) Fibrosis
1-Antitrypsin (1-AT) Deficiency - Maladaptive, Self-Perpetuating Immune Response
o Distal Acinar (Paraseptal) Emphysema o Pathogenic CD4+ TH17
Involves the Distal Acinus
Normal Proximal Acinus Morphology
Multiple, continuous, enlarged - Voluminous Lungs, generally the upper 2/3 are
airspaces (<0.5cm to >2cm) ! Cyst- severely affected.
like structures - Large Apical Blebs/Bullae
o Irregular Emphysema - Abnormally large Alveoli separated by thin Septa
aka Airspace Enlargement with with Focal Centriacinar Fibrosis
Fibrosis - Large Pores of Kohn ! Septa appears floating/
invariably associated with scarring. protruding blindly into alveolar spaces with a
Most common form Club-Shaped End
Asymptomatic & clinically
insignificant Clinical Course
- does not appear until at least 1/3 of the
Pathogenesis functioning Pulmonary Parenchyma is damaged.
- Dyspnea = 1st Sx (insidious & progressive)
 - Cough & Wheezing, Weight Loss
- Barrel-Chest with prolonged expiration; sits
forward in a hunched-over position; pursed-lip
breathing
- Expiratory Airflow Limitation = key to Dx
- Severe Emphysema = slight cough, severe
overdistention, low diffusion capacity, normal
blood gas values at rest ! overventilation &
remain well oxygenated ! PINK PUFFERS
- Cor Pulmonale & Congestive Heart Failure = Poor
Prognosis!!
- Death is due to:
o Respiratory Acidosis & Coma
o Right-Sided Heart Failure
o Massive Lung Collapse r/t Pneumothorax
- Tx = Bronchodilators, Steroids, Bullectomy, Lung
Volume Reduction Surgery, & Lung Transplantation
Compensatory Hyperinflation (Emphysema)
- dilation of Alveoli without destruction of septal
walls in response to loss of Lung substance
elsewhere (e.g. Hyperexpansion of residual Lung
Parenchyma after surgical removal of diseased
Lung/Lobe).
Obstructive Overinflation
- Lung expansion r/t trapped air (subtotal
obstruction by tumor/foreign object)
- Congenital Lobar Overinflation = r/t hypoplasia
of Bronchial Cartilage & congenital cardiac & lung
abnormalities
- Ball-Valve action of obstructive agent ! air
enters on inspiration but cannot leave on
expiration
- Total Bronchial obstruction with air brought by
collateral ventilation
o Pores of Kohn
o Canals of Lambert (Accessory
Bronchioalveolar Connections)
- LIFE-THREATENING EMERGENCY
Bullous Emphysema
- large Subpleural Blebs/Bullae (spaces > 1cm)
- localized accentuations of Emphysema
o near the Apex
o r/t Old Tuberculous Scarring
- rupture ! Pneumothorax
Interstitial Emphysema
- entrance of air into the CT Stroma of the Lungs,
Mediastinum, or SC Tissue r/t Alveolar Tears
o chest wounds
o fractured rib puncturing the Lung
o coughing with bronchiolar obstruction !
sharply increased pressures
CHRONIC BRONCHITIS
- persistent cough with sputum production at least
3 months in 2 consecutive years, without other
identifiable cause.
- Persistence may lead to:
o COPD
o Cor Pulmonale & Heart Failure
o Atypical Metaplasia & Dysplasia of
Respiratory Epithelium ! Cancerous
Transformation
Pathogenesis
- r/t long-standing irritation by inhaled smokers
(e.g. tobacco, dust)
- Earliest Features:
o Hypersecretion of Mucus in Large Airways
(c/o Proteases)
o Hypertrophy of Submucosal Glands in
Trachea & Bronchi (protective
metaplastic reaction)
- Marked increase in Goblet Cells (Bronchi &
Bronchioles) ! excessive mucus production !
airway obstruction
- Alterations in small airways (<2-3mm) ! impt &
early manifestations
- Infection = 2 role; produces acute exacerbations
o Cigarette Smoking intergeres with Ciliary
action, causing direct damage to airway
epithelium, & inhibits bacterial clearance
by bronchial & alveolar WBCs.
Morphology
- Hyperemia, swelling & edema of mucous
membranes with excessive mucinous/
mucopurulent secretions.
o Major change is HYPERPLASIA OF MUCOUS
GLANDS
- Reid Index = ratio of Mucous Gland layer
thickness to the thickness of the wall between
the epithelium & cartilage.
o N = 0.4; increased in Chronic Bronchitis
- Bronchial Epithelium = Squamous Metaplasia &
Dysplasia
- Marked narrowing of Bronchioles r/t mucus
plugging, inflammation, & fibrosis
- Bronchiolitis Obliterans = obliteration of lumen
r/t fibrosis
Clinical Features
- Cardinal Sx = PERSISTENT COUGH with SPUTUM
PRODUCTION
- Dyspnea on exertion
- BLUE BLOATERS = Hypercapnea, Hypoxemia, &
Mild Cyanosis
- Severe = Cor Pulmonale with Cardiac Failure
- Death r/t impaired respiratory function r/t
superimposed acute infxn
ASTHMA
- chronic airway inflammatory disorder causing
recurrent episodes of Wheezing, Chest Tightness,
Breathlessness, & Cough
o either Night or Early Morning
o reversible widespread but variable
Bronchoconstriction & Airflow Limitation
- Hallmarks:
o Increased Airway Responsiveness to
Stimuli ! Episodic Bronchoconstriction
o Bronchial Wall Inflammation
o Increased Mucus Secretion
 - Status Asthmaticus = state of unremitting attacks
in long-term asthma with asymptomatic periods
in between.
Atopic Asthma
- most common type
- Type 1 IgE-Mediated Hypersensitivity Reaction
- Begins in childhood & triggered by environmental
allergens
- (+) Family History
- skin test results in an immediate Wheal-and-Flare
reaction
- Dx = Allergen Sensitization by Serum
Radioallergosorbent Tests (RAST) ! identifies
specific IgE
Non-Atopic Asthma
- no evidence of allergen sensitization; (-) Skin Test
- r/t Respiratory Infections by Viruses
o hyperirritability of the Bronchial Tree
o inflammation lowers the threshold of the
subepithelial vagal receptors to irritants.
Drug-Induced Asthma
- sensitivity to pharmacologic agents
- Aspirin-Sensitive Asthma = sensitivity to small
doses of Aspirin & other NSAIDs ! asthmatic
attacks & urticarial
o Inhibition of Arachidonic Acid Metabolism
Cyclooxygenase Pathway without
affecting the Lipoxygenase route !
Bronchoconstrictor Leukotriene
elaboration
Occupational Asthma
- c/o fumes, organic & chemical dusts, gases, &
other chemicals
- Type I Reactions, Bronchoconstrictor liberation, &
hypersensitivity
Pathogenesis
- genetic predisposition to Type I Hypersensitivity
(Atopy) & exposure to environmental triggers
o development of strong TH2 Reactions
against Allergens ! Cytokine secretion !
Allergic Inflammation & IgE production by
B Cells
o IL-4 = stimulates IgE production
o IL-5 = activates local Eosinophils
o IL-13 = stimulates mucus secretion &
promotes IgE production by B Cells
- Early-Phase (Immediate Hypersensitivity)
Reaction
o Bronchoconstriction, increased mucus
production, & vasodilation with increased
vascular permeability
- Late-Phase Reaction = inflammation with WBC
recruitment
o Eosinophils, Neutrophils, T Cells
o Eotaxin = chemoattractant & activator of
Eosinophils ! Major Basic CHON of
Eosinophils cause epithelial damage !
airway constriction
- Mediators implicated in the asthmatic response
include:
o Leukotrienes C4, D4, & E4 =
bronchoconstriction, increased vascular
permeability, & increased mucus
secretion
o Acetylcholine = airway smooth muscle
constriction by direct muscarinic receptor
stimulation
o Histamine = bronchoconstriction
o Prostaglandin D = bronchoconstriction &
vasodilation
o Platelet-Activating Fx (PAF) = Platelet
Aggregation & release of Histamine &
Serotonin
o IL-1, TNF, IL-6, Eotaxin, Neuropeptides,
NO, Bradykinin, & Endothelins
- Airway Remodeling = structural changes in the
bronchial wall r/t repeated bouts of allergen
exposure & immune reactions.
o Overall Airway Wall Thickening
o Hypertrophy & Hyperplasia of Bronchial
Smooth Muscle
o Epithelial Injury
o Increased Airway Vascularity
o Increased Subepithelial Mucus Gland
Hypertrophy/Hyperplasia
o Subepithelial Collagen Deposition !
Fibrosis
- Hygiene Hypothesis = eradication of infections
may promote allergic & other harmful immune
responses
Genetics of Asthma
- Chromosome 5q near the Gene Cluster encoding
the Cytokines IL-3, IL-4, IL-5, IL-9, & IL-13 & IL-14
receptor.
o Connection between several of the genes
present & mechanisms of IgE regulation
o Mast Cell & Eosinophil Growth &
Differentiation
o CD14 = TT Genotype is assoc. with
reduced IgE levels & risk of Asthma &
Atopy ! TH2 Type of Endotoxin Level !
more brisk IgE production ! Allergy
- Class II HLA Alleles
- ADAM-33 Polymorphisms accelerate proliferation
of Bronchial Smooth Muscle Cells & Fibroblasts !
Bronchial Hyperreactivity & Subepithelial Fibrosis
! declining Lung Function
- 2-Adrenergic Receptor Gene & IL-4 Receptor
Gene
- Chitinase = cleaves Chitin (in Parasites & Fungal
Cell Walls)
Morphology
- Status Asthmaticus = overinflation with small
Atelectasis ! overdistention of Lungs ! death
- Occlusion of Bronchi & Bronchioles by Thick,
Tenacious Mucus Plugs
- Curschmann Spirals = spiral-shaped mucus plugs
resulting from mucus plugging in subepithelial
mucous gland ducts later extruded or bronchiolar
plugs.
- Charcot-Leyden Crystals = collections of
crystalloid made up of Eosinophil
Lysophospholipase Binding CHON (Galectin-10)
Clinical Course
- Chest Tightness, Dyspnea, Wheezing, & Cough
(with/without Sputum Production)
- Increased airflow obstruction, difficulty with
exhalation, & elevated eosinophil count
- Eosinophils, Curschmann Spirals, & Charcot-
Leyden Crystals in Sputum (Atopic Asthma)
BRONCHIECTASIS
- permanent dilation of Bronchi & Bronchioles r/t
destruction of Muscle & Elastic Tissue assoc. with
Chronic Necrotizing Infections.
- Congenital/Hereditary Conditions
o Cystic Fibrosis
o Intralobar Sequestration of Lung
o Immunodeficiency States
o Primary Ciliary Dyskinesia
o Kartagener Syndrome
- Post-Infectious Conditions
- Bronchial Obstruction
- Other Conditions (RA, SLE, IBD, Post-
Transplantation)
Etiology & Pathogenesis
- Obstruction & Infection ! Full-Fledged Lesions
- Impaired Normal Clearing Mechanisms ! pooling
of secretions distal to the obstruction ! Airway
inflammation with necrosis, fibrosis, & airway
dilation
- Cystic Fibrosis = Ion Transport defect !
defective mucociliary action ! accumulation of
thick viscid secretions ! obstruction ! bacterial
infections ! airway damage ! Bronchiolitis
Obliterans
- Primary Ciliary Dyskinesia = AR; poorly
functioning cilia ! secretion retention &
recurrent infection
- Kartagener Syndrome = Bronchiectasis, Sinusitis,
& Situs Inversus or Partial Lateralizing
Abnormality
- Allergic Bronchopulmonary Aspergillosis =
hypersensitivity to Aspergillus Fumigatus; high
IgE levels, antibodies to Aspergillus, intense
airway inflammation, & mucus plug formation
o IL-10 & Neutrophil-mediated
inflammation
o Periods of exacerbation & remission
Morphology
- usually affects the Lower Lobes bilaterally
- airway dilation (up to 4x normal)
- intense acute & chronic inflammatory exudation
within the bronchial & bronchiolar walls with
desquamation of lining epithelium & extensive
areas of necrotizing ulceration.
- Pseudostratification of Columnar Cells or
Squamous Cell Metaplasia
- Lung Abscess formation & Fibrosis
- Mixed flora can be cultured
Clinical Course
- severe persistent cough, expectoration of foul-
smelling & sometimes bloody sputum, dyspnea,
orthopnea, & life-threatening Hemoptysis
- Paroxysmal Cough when rising in the morning
(position changes lead to drainage of Pus &
secretion collections)
- Cx = Cor Pulmonale, Brain Abscess, Amyloidosis
- Tx = Antibiotics, Physical Therapy
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CHRONIC DIFFUSE (RESTRICTIVE) DISEASES
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- inflammation & fibrosis of the Pulmonary CT
(Peripheral & Delicate Interstitium of the Alveolar
Walls)
- dyspnea, tachypnea, end-inspiratory crackles, &
cyanosis without wheezing or airway obstruction
- reduced CO diffusing capacity, Lung Volume, &
Compliance
- Chest Radiograph = Bilateral Infiltrative Lesions
(Small Nodules, Irregular Lines, or GROUND GLASS
SHADOWS) ! Infiltrative
- Cx = 2 Pulmonary Hypertension, RSHF, Cor
Pulmonale
- End-Stage Lung/Honeycomb Lung = advanced
form resulting from scarring & gross destruction
Idiopathic Pulmonary Fibrosis
Non-Specific Interstitial
FIBROSING Pneumonia
DISEASES
Cryptogenic Organizing
Pneumonia
Associated CT Diseases
Pneumoconiosis
Drug Reactions
Radiation Pneumonitis
GRANULOMATOUS Sarcoidosis
DISEASES
Hypersensitivity Pneumonia
EOSINOPHILIC DISEASE
SMOKING-RELATED Desquamative Interstitial
DISEASES Pneumonia
Respiratory Bronchiolitis-
Associated Interstitial Lung
Disease
PULMONARY ALVEOLAR PROTEINOSIS
IDIOPATHIC PULMONARY FIBROSIS (IPF)
- aka Cryptogenic Fibrosing Alveolitis
- histologic pattern = Usual Interstitial Pneumonia
(UIP)
- Repeated Cycles of Epithelial Activation/Injury by
unidentified agent.
o Inflammation & induction of TH2 Type Cell
Response
o Exuberant fibroblastic/myofibroblastic
proliferation ! FIBROBLASTIC FOCI
 o TGF-1 = fibrogenic & is released from
injured Type 1 Alveolar Epithelial Cells;
favors transformation of Fibroblasts into
Myofibroblasts & deposition of Collagen &
ECMs; negatively regulates Telomerase
activity ! Epithelial Cell Apoptosis &
Death-Repair Cycle
o Decreased Caveolin-1 (inhibits pulmonary
fibrosis by limiting TGF-1)
Morphology
- COBBLESTONED PLEURAL SURFACE
- Fibrosis (Firm, Rubbery White Areas) of the Lung
Parenchyma
o Lower lobe predominance with istribution
in the Subpleural Regions & Interlobular
Septa
- Hallmark = PATCHY INTERSTITIAL FIBROSIS
- Earliest Lesion = Fibroblastic Foci
- Honeycomb Fibrosis = cystic spaces lined by
Hyperplastic Type II Alveolar Pneumocytes/
Bronchiolar Epithelium
Clinical Course
- insidious; gradually increasing Dyspnea on
Exertion & Dry Cough
- 40-70 years old
- Hypoxemia, Cyanosis, Clubbing
- Gradual deterioration of pulmonary status
- Tx = LUNG TRANSPLANT ONLY
NON-SPECIFIC INTERSTITIAL PNEUMONIA (NSIP)
- better prognosis than UIP (46-55 y.o)
- Cellular Pattern = mild to moderate chronic
interstitial inflammation with lymphocytes & few
plasma cells
- Fibrosing Pattern = diffuse or patchy interstitial
fibrosing without temporal heterogeneity; no
Fibroblastic Foci & Honeycombing
- Dyspnea & Cough
CRYPTOGENIC ORGANIZING PNEUMONIA
- synonymus with Bronchiolitis Obliterans
Organizing Pneumonia
- Cough & Dyspnea with Subpleural/Peribronchial
Patchy Areas of Airspace Consolidation
- Polypoid Plugs of Loose Organizing CT (Masson
Bodies) within Alveolar Ducts, Alveoli, &
Bronchioles
- Self-Limiting; Tx= Oral Steroids for 6 months or
longer
PULMONARY INVOLVEMENT IN CONNECTIVE TISSUE
DISEASES
- Rheumatoid Arthritis = 30-40%; Chronic Pleuritis
with/without Effusion, Diffuse Interstitial
Pneumonitis & Fibrosis, Intrapulmonary
Rheumatoid Nodules, or Pulmonary Hypertension
- Systemic Sclerosis (Scleroderma) = diffuse
interstitial fibrosis
- Lupus Erythematosus = patchy, transient,
parenchymal infiltrates, severe Lupus
Pneumonitis
- Dermatomyositis-Polymyositis & Mixed CT
Diseases
PNEUMOCONIOSES
- Non-Neoplastic Lung rxn to inhalation of mineral
dusts in workplaces
- Includes diseases induced by organic & inorganic
particulates, chemical fumes, & vapors
o Specific airborne agents & air pollution
Pathogenesis
- Amount of Dust retained in the Lung & Airways
o Dust concentration in the air, duration of
exposure, & effectiveness of clearance
mechanisms
o Accumulation is due to disrupted integrity
of Mucociliary Apparatus
o protection by phagocytes are
overwhelmed
- Size, Shape, & Buoyancy of Particles
o 1-5 m = most dangerous; reaches the
terminal small airways & air sacs
- Particle Solubility, Cytotoxicity, & Physiochemical
Reactivity
o The smaller the particles, the soluble it is
in Pulmonary Fluids & reach toxic levels
rapidly ! Acute Lung Injury
o Large particles resist dissolution & persist
in the parenchyma for years.
- Additional Effects of other irritants
- Genetic predisposition
Coal Workers Pneumoconiosis (CWP)
- Silica in Coal Dust ! progressive disease; Carbon
Dust ! complicated lesions
- Asymptomatic Anthracosis
o Most innocuous coal-induced pulmonary
lesion
o Inhaled Carbon ! Alveolar/Interstitial
Macrophages ! Lymphatic CT
- Simple CWP with little or no Pulmonary
Dysfunction
o COAL MACULES (1-2 mm) & COAL
NODULES
o Upper lobes & upper zones of lower lobes
are more heavily involved.
o Centrilobular Emphysema = occurs when
there is dilation of adjacent Alveoli
- Complicated CWP (Progressive Massive Fibrosis/
PMF)
o Characterized by intensely blackened
multiple scars 2-10 cm consisting of dense
collagen & pigment with a necrotic
center r/t local ischemia
- Benign disease with little decrement in Lung
function
- 10% = increased Pulmonary Dysfunction,
Pulmonary Hypertension, & Cor Pulmonale
- no susceptibility to Tuberculosis or Cancer
- increased incidence of Chronic Bronchitis &
Emphysema
Silicosis
- caused by inhalation of Crystalline Silicon Dioxide
(Silica)
o carcinogenic in humans
- most prevalent chronic occupational disease in
the world.
- Occurs in Crystalline (more fibrogenic) &
Amorphous forms
o Quartz = most common (reduced
fibrogenic effect)
- Inhalation ! epithelial cell & macrophage
interaction ! activation & release of mediators
- Early Stage = Tiny, palpable, discrete pale to
blackened nodules in the Upper Zones of the
Lungs ! Hard, Collagenous Scars
o Central softening & cavitation r/t
superimposed Tuberculosis or ischemia
o Central zone of Caseation
- Eggshell Calcification = thin sheets of
calcification in Lymph Nodes
- Progression, expansion, & coalescence ! Massive
Fibrosis ! SOB
- Nodular Lesions consists of CONCENTRIC
HYALINIZED COLLAGEN
- Increased susceptibility to Tuberculosis & Lung
Cancer
- Depressed Cell-Mediated Immunity & Macrophage
Phagocytosis inhibition
Asbestos-Related Diseases
- Asbestos is a family of Crystalline Hydrated
Silicates forming fibers
- Occupational exposure is linked to:
o Localized Fibrous Plaques or Diffuse
Pleural Fibrosis
o Pleural Effusions
o Parenchymal Interstitial Fibrosis
(Asbestosis)
o Lung Carcinoma & Mesotheliomas
o Laryngeal & Other Extrapulmonary
Neoplasms, including Colon Carcinomas
- Disease causation depends on concentration,
shape, size, & solubility
- Serpentine Chrysotile Chemical Form = accounts
most of asbestos
o More flexible & curled structure
o Impacted in the Upper Respiratory
passages
o Removed by Mucociliary Elevator
o More soluble ! leached from the tissues
- Amphibole Form = more pathogenic with respect
to induction of Mesotheliomas (malignant pleural
tumors)
o Greater pathogenicity r/t aerodynamic
properties & solubility
o Straight & stiff ! align themselves in the
airstream ! delivered deeper into the
lungs ! penetrates epithelial cells !
interstitium
- Fibrogenic (increasing doses are associated with
disease incidence)
- Oncogenic effects mediated by Reactive Free
Radicals localizing in the distal Lung close to the
Mesothelial layer.
o Potentially toxic chemicals adsorbed into
asbestos fibers contribute to
oncogenecity
- DIFFUSE PULMONARY INTERSTITIAL FIBROSIS
- Asbestos Bodies = golden brown, fusiform/
beaded rods with translucent center consisting of
Asbestos Fibers coated with an Iron-containing
proteinaceous material.
o Arises when Macrophages attempt to
phagocytize asbestos fibers
o Iron is from Phagocyte Ferritin
o Ferruginous Bodies = inorganic
particulates coated with Iron-CHON
Complexes
- Fibrosis around Respiratory Bronchioles & Alveolar
Ducts ! enlarged airspaces ! Honeycombing &
Fibroblastic Foci
- Begins in the LOWER LOBES & SUBPLEURALLY
- Pleural Plaques = most common manifestation;
well-circumscribed plaques of dense Collagen &
contains Calcium.
o Develops in the Anterior & Posterolateral
Parietal Pleura & Diaphragm Domes
- Serous Pleural Effusions (may be bloody)
- Dyspnea = 1st manifestation; provoked by
exertion & later at rest; accompanied by Cough
with Sputum production
- Chest X-Ray = irregular linear densities in both
Lower Lobes
DRUG-INDUCED LUNG DISEASES
Bleomycin & Amiodarone Pneumonitis & Fibrosis
Methotrexate & Nitrofurantoin Hypersensitivity
Pneumonitis
Aspirin & -Antagonists Bronchospasm
RADIATION-INDUCED LUNG DISEASES
- Cx of therapeutic Thoracic Tumor Radiation
(Lung, Esophagus, Breast, Mediastinum)
- Acute Radiation Pneumonitis = 10-20%; 6 months
after fractionated irradiation; Lymphocytic
Alveolitis or Hypersensitivity Pneumonitis
o Fever, Dyspnea out of proportion to
irradiated Lung Volume, Pleural Effusion,
& Radiologic Infiltrates
o Steroid Therapy resolves Sx completely
- Chronic Radiation Pneumonitis (Pulmonary
Fibrosis) = consequence of repair of injured
endothelial & epithelial cells within the radiation
portal.
o diffuse Alveolar damage (Atypia of
Hyperplastic Type II Cells & Fibroblasts)
- Epithelial Cell Atypia & Foam Cells within Vessel
Walls
-
SARCOIDOSIS
- systemic disease of unknown cause characterized
by NONCASEATING GRANULOMAS in tissues &
organs
- Chest X-Ray = (90%) Bilateral Hilar
Lymphadenopathy or Lung Involvement
o Eyes & Skin lesions occur next in
frequency
 - Disease of disordered immune regulation in
genetically predisposed individuals exposed to
environmental agents
- Immunological Factors = development of Cell-
Mediated Response to an unidentified antigen c/o
CD4+ Helper T-Cells
o Intra-Alveolar & Interstitial accumulation
! CD4/CD8 T-Cell ratios 5:1 to 15:1
o Increased T-Cell derived TH1 Cytokines
(IL-2 & IFN-) ! T-Cell expansion &
Macrophage Activation
o IL-8, TNF, & Macrophage Inflammatory
CHON 1 ! recruitment of additional T-
Cells & Monocytes; granuloma formation
- Systemic Immunological Abnormalities
o Anergy to common skin test antigens
o Polyclonal Hypergammaglobulinemia
- Genetic Factors = HLA-A1 & HLA-B8
- Environmental Factors = most tenacious of all
associations
o Mycobacteria, Propionibacterium Acne, &
Rickettsia
o No unequivocal evidence that Sarcoidosis
is caused by an infectious agent
Morphology
- Classic Well-Formed NONCASEATING GRANULOMAS
with aggregates of epithelioid cells & Langhans/
Foreign Body-Type Giant Cells
o Later replaced by Hyaline Fibrous Scars
o Central Necrosis
o Schaumann Bodies = laminated
concretions of Calcium & Proteins
o Asteroid Bodies = Stellate Inclusions
- Lungs = common site of involvement
o Coalescence of granulomas produce small
nodules that are palpable or visible as 1-2
cm, non-caseating, non-cavitated
consolidations
o Strong tendency of lesions to heal in the
Lungs ! fibrosis & hyalinization
- Lymph Nodes (Hilar & Mediastinal Nodes) =
enlarged, discrete, & calcified; Tonsils involved
-1/3 of cases
- Spleen = (3/4 involved) granulomas coalesce to
form small nodules
- Liver = less likely affected than the Spleen;
moderately enlarged with scattered Granulomas,
more in Portal Triads; Dx = Needle Biopsy
- Bone Marrow = (1/5 involved) Phalangeal Bones
! small circumscribed areas of Bone Resorption
& diffuse reticulated pattern with Bony Shaft
widening or new bone formation in outer surfaces
- Skin Lesions = 1/3 to of cases; discrete
subcutaneous nodules, focal slightly elevated
erythematous plaques, slightly reddened &
scaling flat lesions resembling SLE
- Eyes & Salivary Glands = 1/5 to ; Iritis/
Iridocyclitis, Corneal Opacities, Glaucoma, &
Total Vision Loss; Lacrimal Gland inflammation;
Mikulicz Syndrome
- Muscles = ASx; muscle weakenss, aches,
tenderness, & fatigue
Clinical Course
- Protean clinical d/e (varying severity &
inconstant lesion distribution)
- Insidious respiratory abnormalities (SOB, cough,
chest pain, hemoptysis) or constitutional S/Sx
(fever, fatigue, weight loss, anorexia, night
sweats)
- Progressive chronicity or periods of activity
interspersed with remissions (sometimes
permanent) that may be spontaneous or induced
by Steroid Therapy
HYPERSENSITIVITY PNEUMONITIS (ALLERGIC
ALVEOLITIS)
- spectrum of immunologically mediated,
predominantly interstitial, Lung disorder c/o
intense (prolonged) organic antigen exposure.
o Bronchoalveolar Lavage show increased
Proinflamatory Chemokine levels & T-
Lymphocytes
o Specific Antibodies suggestive of Type III
(Immune Complex) Hypersensitivity
o Complement & Immunoglobulins
demonstrated within Vessel Walls by
Immunofluorescence
o Non-Caseating Granulomas ! Type IV (T
Cell-Mediated) Delayed-Type
Hypersensitivity
- Abnormal sensitivity or heightened reactivity to
antigen involving primarily the Alveoli.
o Inhalation of Organic Dust containing
antigens
- Farmers Lung = exposure to dusts from
harvested humid, warm hay
- Pigeon Breeders Lung (Bird Fanciers Disease) =
CHONs from serum, excreta, or feathers of birds
- Humidifier/Air-Conditioner Lung = thermophilic
bacteria in heated water reservoirs
Morphology
- subacute & chronic changes centered on
Bronchioles
- Interstitial Pneumonitis (Lymphocytes, Plasma
Cells, & Macrophages)
- Non-Caseating Granulomas (2/3 of patients)
- Interstitial Fibrosis, Honeycombing, &
Obliterative Bronchiolitis
- Intra-Alveolar Infiltrates
Clinical Features
- recurring episodes of fever, dyspnea, cough, &
leukocytosis
- diffuse & nodular infiltrates
- acute restrictive d/o via Pulmonary Function
Tests
- Chronic Form = progressive respiratory failure,
dyspnea, & cyanosis with decreased Total Lung
Capacity & Compliance
PULMONARY EOSINOPHILIA
- infiltration of Eosinophils recruited in part by
elevated Alveolar levels of Eosinophil Attractants
(e.g. IL-5)
Acute Eosinophilic Pneumonia with Respiratory Failure
- idiopathic acute illness
- rapid onset with fever, dyspnea, & hypoxemic
respiratory failure
- Chest X-Ray = diffuse infiltrates
- Bronchoalveolar lavage fluid contains > 25%
Eosinophils
- Prompt response to Corticosteroids
Simple Pulmonary Eosinophilia (Lffler Syndrome)
- transient pulmonary lesions, eosinophilia in
blood, & benign clinical course; CT Scan =
irregular intrapulmonary densities
- thickened Alveolar Septa
- no vasculitis, fibrosis, or necrosis
Chronic Eosinophilic Pneumonia
- focal areas of cellular consolidation (peripheral
Lung fields)
- heavy aggregates of Lymphocytes & Eosinophils
- High Fever, Night Sweats, & Dyspnea
- Responds to Corticosteroid Therapy
Secondary Eosinophilia
- occurs in parasitic, fungal, & bacterial infections;
hypersensitivity pneumonitis, drug allergies, &
asthma, allergic bronchopulmonary aspergillosis,
& vasculitis
DESQUAMATIVE INTERSTITIAL PNEUMONIA
- Smokers Macrophages = accumulation of large
number of macrophages with abundant cytoplasm
containing dusty brown pigment in the airspaces
o Finely granular Iron may be seen
o May contain Lamellar Bodies composed of
Surfactant c/o Necrotic Type II
Pneumocytes
- Thickened alveolar septa lined with plump,
cuboidal pneumocytes
- Interstitial Fibrosis & Emphysema may be present
- 4th-5th decade of life; M>F (2:1); Cigarette
Smoking
- Insidious onset of Dyspnea & Dry Cough
associated with Clubbing of Digits; Pulmonary Fxn
Test = mild restrictive abnormality with moderate
reduction of CO2 Diffusing Capacity
- 100% responds to Steroid Therapy & Smoking
cessation
RESPIRATORY BRONCHIOLITIS-ASSOCIATED INTERSTITIAL
LUNG DISEASE
- pigmented intraluminal macrophages within the
1st & 2nd-Order Respiratory Bronchioles; M>F (2:1)
- significant Pulmonary Sx, Abnormal Pulmonary
Fxn, & Imaging Abnormalities; 4th-5th Decades;
average of 30 pack-years
- Patchy & Bronchiolocentric Distribution changes
o Lympocytes & Histiocytes
- Smokers Macrophages
- Mild Peribronchiolar Fibrosis
- Centrilobular Emphysema (not severe)
- Gradual onset of Dyspnea & Cough
- Smoking Cessation = Improvement
PULMONARY ALVEOLAR PROTEINOSIS (PAP)
- Chest X-Ray = Bilateral Patchy Asymmetric
Pulmonary Opacifications
- Histology = Accumulation of acellular Surfactant
in intra-alveolar & bronchiolar spaces
- Acquired PAP = 90%, lacks familial predisposition
o Caused by Anti-GM-CSF Antibody, leading
to functional GM-CSF Deficiency
o Autoimmune disorder
- Congenital PAP = immediate-onset neonatal
respiratory distress
o ABCA3, SP-C, GM-CSF, & GM Receptor
Chain mutation
o Progressive respiratory distress shortly
after birth
o Tx = LUNG TRANSPLANT (death between
3-6 months if without transplant)
- Secondary PAP = hematopoietic d/o,
malignancies, immunodeficiency d/o, lysinuric
CHON intolerance, & acute silicosis & other
inhalational syndromes
- Insidious onset of respiratory difficulties, cough,
& abundant sputum with chunks of gelatinous
material; febrile illnesses
- Progressive dyspnea, cyanosis, & respiratory
insufficiency
- Whole-Lung Lavage = standard of care
- GM-CSF Therapy = 50% effective
Morphology
- peculiar homogenous, granular precipitate within
the Alveoli ! focal-to-confluent consolidation of
large areas of Lungs with minimal inflammatory
reactions
- marked increase in weight & size of Lung
- Alveolar Precipitate = periodic acid-Schiff (+)
with Cholesterol Clefts
- Immunohistochemical Stains = Surfactant CHONs A
&C
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DISEASES OF VASCULAR ORIGIN
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-----------------------------------
PULMONARY EMBOLISM, HEMORRHAGE, & INFARCTION
- Blood Clots occluding Large Pulmonary Arteries
are Embolic in origin.
o Usually rare
o Develops in the presence of Pulmonary
Hypertension, Pulmonary Atherosclerosis
& Heart Failure
o Deep Leg Vein Thrombosis = 95%
- Rx Fx = 1/2 Hypercoagulable States, Indwelling
Central Venous Lines (nidus for Right Atrial
Thrombus)
- Pathophysiology depends on the extent of
Pulmonary Arterial Blood Flow obstruction, size of
occluded vessel, number of emboli, overall
Cardiovascular status, & release of Vasoactive Fx.
o Respiratory Compromise = due to non-
perfused but ventilated segments
o Hemodynamic Compromise = increased
resistance to pulmonary blood flow c/o
embolic obstruction

Morphology
- Large Emboli ! Main Pulmonary Artery ! Saddle
Embolus
o sudden death r/t blood flow blockage
through the Lungs
o Acute Cor Pulmonale = acute RSHF
- Small Emboli ! peripheral vessels ! Hemorrhage
o 10% = Infarction (r/t inadequate
circulation)
o raised, red-blue area (Early Stage) ! lyse
in 48 hours ! paler ! red-brown r/t
Hemosiderine ! gray-white peripheral
zone ! contracted scar
- Lines of Zahn = diff. Pulmonary Emboli from
Post-Mortem Clots
- Septic Infarcts = infarction modified by intense
neutrophilic inflammatory reaction (infected
embolus)
Clinical Course
- Electromechanical Dissociation = ECG with
rhythm but no palpable pulses because no blood
is entering the pulmonary arterial circ.
o Survival mimics MI with severe chest
pain, dyspnea, shock, fever, & increased
serum lactate dehydrogenase
- Small Emboli = transient chest pain & cough
o Infarct = dyspnea, tachypnea, fever,
chest pain, cough, hemoptysis
o Fibrinous Pleuritis = Pleural Friction Rub
- Chest Radiograph = may be normal or disclose a
pulmonary infarct
o 12-36 hours = Wedge-Shaped Infiltrate
- Dx = Spiral CT Angiography, V/P Scan, Pulmonary
Angiographu, Duplex Ultrasonography
- Contraction & Fibrinolysis = resolution
- Unresolved = Pulmonary Hypertension, Pulmonary
Vascular Sclerosis, & Chronic Cor Pulmonale
- 30% chance of developing a 2nd Embolus
Prevention
- early ambulation in post-operative & postpartum
patients
- Elastic Stockings & Graduated Compression
Stockings (bedridden)
- Anti-Coagulants with Thrombolysis
- Filter insertion (Umbrella) or ligation of
Inferior Vena Cava
PULMONARY HYPERTENSION
- occurs when Mean Pulmonary Pressure reaches
of Systemic levels.
o Pulmonary Arterial Hypertension
o Pulmonary Hypertension with Left Heart
Disease
o Pulmonary Hypertension with associated
with Lung Diseases &/or Hypoxemia
o Pulmonary Hypertension due to Chronic
Thrombotic &/or Embolic Disease
o Miscellaneous Pulmonary Hypertension
- Associated with structural cardiopulmonary
conditions increasing Pulmonary Blood Flow/
Pressure, Pulmonary Vascular Resistance, or Left
Heart Blood Flow Resistance:
o Chronic Obstructive/Interstitial Lung
Diseases
o Antecedent Congenital/Acquired Heart
Disease
o Recurrent Thromboemboli
o Connective Tissue Diseases
o Obstructive Sleep Apnea
- Idiopathic Pulmonary Arterial Hypertension =
PH excluding all known cases of increased
pulmonary pressure
- Familial Pulmonary Arterial Hypertension = AD;
incomplete penetrance (10-20%)
o Bone Morphogenetic Protein Receptor
Type 2 (BMPR2) Signaling Pathway
mutations ! no inhibition of proliferation
& apoptosis
o Modifier Genes & Environmental Triggers
Pathogenesis
- Thromboembolism ! Fibrin ! Biochemical Injury
& L-R Shunts ! Increased Shear & Mechanical
Injury ! Endothelial Cell Dysfunction
- Decreased Prostacyclin & NO & increased
Endothelin ! Pulmonary Vasoconstriction,
Platelet Adhesion & Activation
- Growth Fx & Cytokines ! migration & replication
of Vascular Smooth Muscle Cells & ECM
elaboration
- Ingestion of Crotalaria Spectabilis pant (Bush
Tea), Aminorex (appetite depressant),
adulterated Olive Oil, & Fenfluramine &
Phentermine (Anti-Obesity Drugs)
Morphology
- Medial Hypertrophy of Muscular & Elastic
Arteries, Pulmonary Artery Atheromas, & Right
Ventricular Hypertrophy
- Many organizing/recanalized Thrombi = recurrent
Pulmonary Emboli
- Diffuse Pulmonary Fibrosis or Severe Emphysema
& Chronic Bronchitis = Chronic Hypoxia
- Small Arterial diameter
- Plexiform Lesion = tuft of capillary formations,
producing a network/web spanning the lumens of
dilated thin-walled, small arteries; r/t drugs &
HIV
- Dilated vessels & Arteritis
Clinical Course
- women 20-40 y.o. & young children
- Sx occur in advanced diseases
o Dyspnea & Fatigue
o Chest Pain (Anginal), Severe Respiratory
Distress, Cyanosis, Right Ventricular
Hypertrophy
o Death by decompensated Cor Pulmonale
- Short Course Tx = O2 Supplementation, Calcium
Channel Blockers, Anticoagulation, Digoxin,
Diuretics
- Recent Tx = Prostacyclin Analogues, Endothelial
Receptor Antagonists, Inhaled NO, &
Phosphodiesterase-5 Inhibitors
- LUNG TRANSPLANT & GENE THERAPY
DIFFUSE PULMONARY HEMORRHAGE SYNDROMES
- Hemorrhagic complication of the Lung from
interstitial Lung d/o
Goodpasture Syndrome
- Autoimmune Disease
o Antibodies ! inflammatory destruction of
basement membrane in Renal Glomeruli
& Pulmonary Alveoli ! rapidly
progressive GN & Necrotizing
Hemorrhagic Interstitial Pneumonitis
- Kidney & Lung injury r/t circulating
autoantibodies against non-collagenous domain of
Collagen IV 3 Chain.
- Teens to 20s; M>F; Environmental Insults; HLA
subtype assoc.
- Heavy Lungs with Red-Brown Consolidation
o Focal Necrotic Alveoli with Intra-Alveolar
Hemorrhages
o Hemosiderin-Laden Macrophages
o Fibrous Thickening of Septae
o Type II Pneumocyte Hypertrophy
- Dx = Immunofluorescence (Igb & Complement
deposits along the basement membranes)
- Respiratory Sx (HEMOPTYSIS) & Focal Pulmonary
Consolidations
- Glomerulonephritis ! Rapidly Progressive Renal
Failure
- UREMIA = most common cause of death
- Tx = PLASMAPHERESIS, immunosuppression
Idiopathic Pulmonary Hemosiderosis
- intermittent, diffuse alveolar hemorrhage
- occurs in young children; some in adults
- insidious onset of productive cough, hemoptysis,
anemia, & weight loss associated with diffuse
pulmonary infiltrations
- no anti-basement membrane detected
- may be due to long-term immunosuppression with
Prednisone &/or Azathioprine
Wegener Granulomatosis
- autoimmune disease involving the upper
respiratory tract & Lungs
- HEMOPTYSIS = most common Sx
- Dx = Transbronchial Lung Biopsy
o Necrosis & granulomatous vasculitis may
not be present
- Capillaritis & Scattered, Poorly Formed
Granulomas
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-----------------------------------
PULMONARY INFECTIONS
-----------------------------------------------------------------------
-----------------------------------
- Pneumonia = infection of the Lung Parenchyma
o Classified by specific etiologic agents
(determines treatment)
o Can arise in 7 distinct clinical settings
(Pneumonia Syndromes)
- Local Lung defense mechanisms are interfered by
the ff. factors:
o Loss/Suppression of Cough Reflex (may
lead to Aspiration)
o Mucociliary Apparatus Injury
o Secretion accumulation
o Interference with Phagocytic/Bactericidal
Action of Alveolar Macrophages
o Pulmonary Congestion & Edema
- Innate Immunity & Humoral Immunodeficiency !
increased infections with pyogenic bacteria
- Cell-Mediated Immune Defects ! increased
infections with intracellular microbes & microbes
with very low virulence.
- One type of Pneumonia sometimes predisposes to
another.
- Hematogenous spread from one organ to another
can occur
o 2 Seeding of the Lungs may be difficult
to distinguish from 1 Pneumonia
- Nosocomial Infections (Terminal Pneumonias) may
occur
COMMUNITY ACQUIRED ACUTE PNEUMONIA
- Bacterial Infxn usually follows an upper
respiratory tract Viral Infxn ! Lung Parenchyma
filled with exudate ! Consolidation
(Solidification)
- Fx = Specific Etiologic Agent, Host Reaction, &
Extent of Involvement
Streptococcus Pneumoniae (Pneumococcus)
- most common cause
- Dx = neutrophils with Gram-(+), LANCET-SHAPED
Diplococci
o 20% = Endogenous Flora ! False-(+)
o Blood Culture = more specific but less
sensitive
Haemophilus Influenzae
- pleomorphic, Gram-(-); major cause of life-
threatening acute LRTIs & Meningitis in young
children
- ubiquitous colonizer of the Pharynx
- Encapsulated Form = 5%; secretes Haemocin that
kills Unencapsulated forms
o 6 serotypes (Type a-f)
o Type b = has polyribosephosphate
capsule; most frequent cause of severe
invasive disease
- Unencapsulated Form = 95%
- Non-Typeable Forms = produce Otitis Media,
Sinusitis, & Bronchopneumonia
- Pili promotes adherence to the Respiratory
Epithelium
- Secretes factors that disorganizes ciliary beating
& a protease that degrades IgA
- Pediatric emergency with high mortality rate
o Descending Laryngotracheobronchitis !
airway obstruction ! consolidation
(lobular & patchy)
- Suppurative Meningitis, Acute Purulent
Conjunctivitis (Pink Eye), Septicemia,
Endocarditis, Pyelonephritis, Cholecystitis, &
Suppurative Arthritis; Acute COP Exacerbation
Moraxella Catarrhalis
- bacterial pneumonia in the elderly
- 2nd most common cause of Acute COPD
Exacerbation
- Otitis Media in children
Staphylococus Aureus
- 2 Bacterial Pneumonia following Viral
Respiratory Illnesses
- assoc. with Cx (Empyema & Lung Abscess)
- Rx = Intravenous Drug Abusers (assoc. with
Endocarditis)
- Hospital-Acquired Pneumonia
Klebsiella Pneumoniae
- affects debilitated & malnourished people
(Chronic Alcoholics)
- THICK & GELATINOUS SPUTUM
Pseudomonas Aeruginosa
- Hospital-Acquired Pneumonia
- Cystic Fibrosis; Septicemia = fulminant
Legionella Pneumophila
- Legionnaires Disease, Pontiac Fever
- Flourishes in artificial aquatic environments !
ihalation/aspiration
- Organ Transplant recipients are highly susceptible
- Dx = CULTURE (Gold Standard), Legionella
antigens in urine, (+) Fluorescent Antibody Test
Morphology
- Lobar Bronchopneumonia = PATCHY LUNG
CONSOLIDATION
o Slightly elevated, dry, granular, gray-red
to yellow, & poorly delimited at their
margins.
o Elicits a suppurative, neutrophil-rich
exudate
- Lobar Pneumonia = FIBRINOSUPPURATIVE
CONSOLIDATION
o 4 stages of Inflammatory Response:
Congestion = heavy, boggy, & red
Lungs; vascular engorgement, intra-
alveolar fluid with Neutrophils,
numerous bacteria
Red Hepatization = massive
confluent exudation with
neutrophils, RBCs, & Fibrin; Red,
firm, airless lobe with a liver-like
consistency (Hepatization)
Gray Hepatization = disintegration
of RBCs & persistence of
fibrinosuppurative exudate !
grayish-brown, dry surface
Resolution = enzymatic digestion of
consolidated exudate ! granular,
semifluid debris ! resorbed,
macrophage ingestion,
expectorated, or fibroblast
organization
- Most important clinical stand-point =
Identification of Causative Agent & determine
extent of disease
- Complications include:
o Tissue Destruction & Necrosis ! Abscess
Formation
o Spread of Infection to the Pleural Cavity
! Empyema
o Bacteremic Dissemination to Heart
Valves, Pericardium, Brain, Kidneys,
Spleen, or Joints ! Metastatic Abscess,
Endocarditis, Meningitis, or Suppurative
Arthritis
Clinical Course
- abrupt onset of high fever, shaking chills, &
productive cough (mucopurulent sputum);
occasionally hemoptysis
- Pleuritic Pain & Pleural Friction Rub
- Radiopacity (Lobar Pneumonia) or Focal Opacity
(Bronchopneumonia)
- Dx = Identification of Organism & determination
of Antibiotic Sensitivity (Keystones to appropriate
Tx)
- Tx = Antibiotics (Afebrile with few S/Sx 48-72 hrs)
COMMUNITY-ACQUIRED ATYPICAL (VIRAL &
MYCOPLASMAL) PNEUMONIA
- Primary Atypical Pneumonia = acute febrile
respiratory d/e with patchy inflammatory
changes in the Lungs
o Confined to the Alveolar Septa &
Pulmonary Interstitium
o Moderate amount of sputum, no
consolidation, moderate elevation of
WBCs, & no alveolar exudate
o M. Pneumoniae = most common cause
o Fx = Extremes of Age, Malnutrition,
Alcoholism, & underlying Debilitating
Illnesses
- Attachment of microorganism to URT epithelium
! Cell Necrosis & Inflammatory Response !
damage & denudation of epithelium ! inhibition
of Mucociliary Clearance ! 2 Bacterial
Infections
Morphology
- Patchy Lung (bilateral/unilateral) ! Red-Blue &
Congested
- Interstitial Inflammatory Reaction localized
within Alveolar walls
- Widened & edematous Alveolar Septa with
mononuclear inflammatory infiltrates.
- Intra-Alveolar Proteinaceous Material & Cellular
Exudates
- ARDS Cx = Pink Hyaline Membranes lining the
alveolar wall.
- Superimposed Bacterial Infxn ! Ulcerative
Bronchitis, Bronchiolitis, & Bacterial Pneumonia
Clinical Course
- Severe URTIs or Chest Colds; cough may be
absent
- Fever, Headache, Muscle Aches, & Leg Pains
- Edema & Exudation ! V/P Mismatch

Influenza Infections
- Influenza Virus Type A = infect humans, pigs,
horses, & birds
o Major cause of Pandemic & Epidemic
Influenza
o Antigenic Drift = mutations of
Hemagglutinin & Neuraminidase ! virus
escape host antibodies
o Antigenic Shift = Hemagglutinin &
Neuraminidase replaced with animal
viruses, allowing susceptibility to new
influenza viruses.
- Influenza Virus Type B & C = no Antigenic Drift/
Shift; infects children who develops antibodies
that prevent reinfection.
- Interstitial Myocarditis or Reye Syndrome (after
Aspirin Therapy)
- Avian Influenza = primarily infects Birds.
o Antigenic Type H5N1 = lethal in humans
(60%); r/t close contact with birds
- Mucosal Hyperemia & swelling with
Lymphomonocytic & Plasmacytic infiltration of
the submucosa & mucus secretion overproduction
o Plugging of Nasal Channels, Sinuses, or
Eustachian Tubes ! Suppurative 2
Bacterial Infection
- Laryngotracheobronchitis & Bronchiolitis = vocal
cord swelling & mucus exudation !
superinfection, atelectasis
Human Metapneumovirus (MPV)
- Paramyxovirus assoc. with URTIs & LRTIs of young
children, elderly, & immunocompromised
patients.
- Dx = Transcriptase-PCR
- Tx = Rabivarin, Live Attenuated Vaccines
Severe Acute Respiratory Syndrome (SARS)
- IP = 2-10 Days; c/o Coronavirus
o Human-to-human; infected secretions/
stool
- Dry Cough, Malaise, Myalgias, Fever, & Chills
- Severe Respiratory Disease with SOB, Tachypnea,
Pleurisy
- Dx = PCR or Antibody detection
o Virus levels peak 10 days after onset of
illness
o No measurable antibody response for up
to 28 days
HOSPITAL-ACQUIRED PNEUMONIA
- pulmonary infections acquired during hospital
stay
- common with severe underlying d/e,
immunosuppression, prolonged antibiotic therapy,
or invasive access devices & mechanical
ventilation
- Life Threatening = Enterobacteriaceae &
Pseudomonas species
- Staphylococus Aureus = most common
ASPIRATION PNEUMONIA
- occurs in debilitated patients or those who
aspirate gastric contents while unconscious or
during repeated vomiting.
o Abnormal gag & swallowing reflexes
- Necrotizing type ! fulminant clinical course !
death
- Cx = Lung Abscess
LUNG ABSCESS
- local suppurative process within the Lung
characterized by necrosis of the Lung Tissue.
- 60% = Anaerobic Organisms (Bacteroides,
Fusobacterium, & Peptococcus species)
introduced by:
o Aspiration (most frequent cause;
commonly on the right)
o Antecedent Primary Lung Infection
o Septic Embolism
o Neoplasia
o Miscellaneous (Trauma, Suppuration,
Hematogenous Seeding, etc.)
- Primary Crytpogenic lung Abscess = no
reasonable basis for abscess formation can be
identified
Morphology
- Varies from lesions of a few millimeters to large
cavities of 5-6 cm
- Superimposed saprophytic infections are prone to
flourish within the necrotic debris of the abscess
cavity.
- Continued infxn ! large, fetid, green-black,
multi-locular cavities with poor margin
demarcation (Gangrene of Lungs)
- Cardinal Histologic Change = SUPPURATIVE
DESTRUCTION OF THE LUNG PARENCHYMA WITHIN
THE CENTRAL AREA OF CAVITATION
- Chronic = Fibroblastic proliferation ! Fibrous
Wall
Clinical Course
- Cough, Fever, Copious Foul-Smelling Purulent/
Sanguineous Sputum, Chest Pain, Weight Loss
- Clubbing of Fingers & Toes
- Dx = clinical findings confirmed by Radiology
- Tx = Antimicrobial Therapy (leaves scars)
- Cx = extension into the Pleural Cavity,
Hemorrhage, Brain Abscess/Meningitis (Septic
Emboli), & 2 Amyloidosis (Type AA)
CHRONIC PNEUMONIA
- localized lesion in the immunocompetent patient
with/without regional lymph node involvement
- granulomatous inflammatory rxn c/o bacteria or
fungi
Histoplasmosis
- c/o Histoplasma Capsulatum c/o inhalation of
dust particles from soil contaminated with bird/
bat droppings containing small spores
(Microconidia)
o intracellular parasite of Macrophages
- self-limited & latent 1 Pulmonary involvement
! Coin Lesions
 - Chronic, progressive, 2 Lung Disease localized to Causes of Pulmonary Infiltrates in Immunocompromised
the Lung Apices Hosts
o Cough, Fever, Night Sweats
DIFFUSE INFILTRATE FOCAL INFILTRATE
- Localized lesions in Extrapulmonary Sites
(Mediastinum, Adrenals, Liver, Meninges) Common
- Widely disseminated d/e in Immunocompromised
Patients Cytomegalovirus Gram-Negative Rods
- Epitheloid Cell Granulomas ! Caseation Necrosis Pneumocystis Jiroveci Staphylococcus Aureus
Drug Reactions Aspergillus
! coalesce to produce large areas of
Candida
consolidation but may liquefy Malignancy
- TREE-BARK APPEARANCE = lesions undergoing
fibrosis & concentric calcification with Uncommon
spontaneous/drug control
- Fulminant Disseminated Histoplasmosis = focal Bacteria Cryptococcus
accumulation of mononuclear phagocytes with Aspergillus Mucor
Cryptococcus Pneumocystis Jiroveci
fungal yeasts
Malignancy Legionella Pneumophila
- Dx = culture/identification of fungus, serologic
tests, Antigen Detection in Body Fluids (formed
2-6 weeks after infection) PULMONARY DISEASE IN HUMAN IMMUNODEFICIENCY
VIRUS INFECTION
Blastomycosis - leading cause of mortality & morbidity in HIV-
- c/o Blastomyces Dermatitidis infected individuals.
o soil-inhabiting, dimorphic fungus - Bacterial LRTIs caused by usual pathogens are one
o Central & Southeast United States, of the most serious pulmonary d/o in HIV
Canada, Mexico, Middle East, Africa, & Infection
India o Bacterial Pneumonia are more common,
- Pulmonary Blastomycosis = abrupt illness with more severe, & associated with
productive cough, headache, chest pain, weight bacteremia
loss, fever, abdominal pain, night sweats, - Not all Pulmonary infiltrates are infectious in
anorexia, & chills etiology
o Chest X-Ray = Lobar Consolidation, o Kaposi Sarcoma
multilobar infiltrates, perihilar o Pulmonary Non-Hodgkin Lymphoma
infiltrates, multiple nodules, & military o Primary Lung Cancer
infiltrates - CD4+ T-Cell Count define the risk of infection
- Disseminated Blastomycosis with specific organisms
- Primary Cutaneous Blastomycosis = c/o direct o > 200 cells/mm3 (Pneumocystis
inoculation of organisms in the skin Pneumonia)
- Suppurative Granulomas o < 50 cells/mm3 (Cytomegalovirus &
Mycobacterium Avium Complex
Coccidioidomycosis Infections)
- inhalation of spores of Coccidioides Immitis ! - results from more than one cause
Delayed Type Hypersensitivity - Dx work-up may be more extensive & expensive
- Infective Arthroconidia ! ingested by Alveolar
Macrophages ! blocked fusion of Phagosome & -----------------------------------------------------------------------
Lysosome ! resists intracellular killing -----------------------------------
- 10% = Lung Lesions, Fever, Cough, & Pleuritic PLEURA
Pains with Erythema Nodosum or Erythema -----------------------------------------------------------------------
Multiforme (San Joaquin Valley Fever Complex) -----------------------------------
- thick-walled, non-budding spherules - involvement is often a 2 complication of
- Purulent Lesions with diminished resistance & underlying diseases.
widespread dissemination o 2 Infections & Pleural Adhesions are
findings at Autopsy
PNEUMONIA IN THE IMMUNOCOMPROMISED HOST - important 1 Disorders include:
- Pulmonary Infiltrate with/without signs of o Primary Intrapleural Bacterial Infections
Infection o Primary Neoplasm of Pleura
- Classified according to the etiologic agent: (Mesothelioma)
o Bacterial PLEURAL EFFUSION
o Viral - normally, no > 15 ml of serous, relatively
o Fungal acellular, clear fluid lubricates the pleural space.
- Accumulation of pleural fluid occurs with:
o Increased Hydrostatic Pressure
(Congestive Heart Failure)
o Increased Vascular Permeability
(Pneumonia)
 o Decreased Osmotic Pressure (Nephrotic
Syndrome) PNEUMOTHORAX
o Increased Intrapleural (-) Pressure - air/gas in the Pleural Cavities
(Atelectasis) - Spontaneous Pneumothorax = complicates any
o Decreased Lymphatic Drainage pulmonary disease that ruptures an alveolus.
(Mediastinal Carcinomatosis) o May be caused by an abscess cavity
communicating directly with the Pleural
Inflammatory Pleural Effusions (Pleuritis) Space or with the Lung Interstitial Tissue
- Fibrinous Exudations reflect a later, more severe ! escape of air
exudative reaction. o Associated with Emphysema, Asthma, &
- Serous/Serofibrinous Exudate = earlier Tuberculosis
developmental phase - Traumatic Pneumothorax = r/t perforating injury
o RA, Disseminated Lupus Erythematosus, to chest wall
Uremia, Diffuse Systemic Infections, & - Spontaneous Idiopathic Pneumothorax = r/t
other Systemic Disorders & Metastatic rupture of small, peripheral, apical, subpleural
Pleural involvement; Therapeutic blebs.
Radiation o Subsides spontaneously as air is resorbed.
o Fluid exudate is resorbed with resolution o Recurrent attacks are common &
or organization of the fibrinous disabling
compartment - Tension Pneumothorax = due to lung collapse,
- Common causes are inflammatory diseases of the where the defect acts as a flap vale & permits
Lungs entrance of air during inspiration but fails to
- Empyema = purulent pleural exudate escape during expiration, acting as a pump that
o Bacterial/mycotic seeding of the Pleural creates a progressive increasing pressure !
Space via contiguous spread of organisms compression
from intrapulmonary infection or
lymphatic/hematogenous dissemination.
o Loculated, yellow-green, creamy pus with
neutrophils mixed with other WBCs.
o May accumulate in large volumes
(500-1000 ml)
o May form dense, tough fibrous adhesions
that onliterate the pleural space or
envelope the lungs ! pulmonary
expansion restriction
- True Hemorrhagic Pleuritis = sanguineous
inflammatory exudates
o Infrequent & is found in hemorrhagic
diatheses, rickettsial diseases, &
neoplastic involvement of the pleural
cavity

Non-Inflammmatory Pleural Effusions

- Hydrothorax = non-inflammatory clear/straw-
colored serous fluid collections within the Pleural
Cavities
o May be unilateral/bilateral
o CARDIAC FAILURE = most common cause;
with Pulmonary Congestion & Edema
o Renal Failure, Liver Cirrhosis
- Hemothorax = escape of blood into the Pleural
Cavity
o Fatal Cx of ruptured AAA or Vascular
Trauma
o May occur Post-Operatively
o Readily identifiable by large clots
accompanying the fluid component of
blood
- Chylothorax = accumulation of Chyle in the
Pleural Cavity
o Milky white fluid due to finely emulsified
fats.
o Caused by Thoracic Duct trauma or
obstruction, rupturing major Lymphatic
Ducts