Pulmonary Pathology

Pulmonary Patholgy

By

The Dark Horse

ATSU-SOMA

Two functional components of the respiratory system

• Conducting system– For transport of gases

– Nasal cavity -> pharynx -> larynx -> trachea -> bronchi

• Respiratory portion– Site of gas exchange

in the alveoli

Respiratory Histology

Conducting Portion Histology• Characterized by ciliated pseudostratified

columnar epithelium rich in goblet cells from the nasal cavity to the bronchi

– As conducting passages branch, height of the epithelium decreases to a ciliated simple columnar to cuboidal

– Goblet cells give a seromucinous secretion that are moved easily by ciliary action and eliminate inhaled particles/debris; act as first line of defense against invasive pathogens

– Connective tissue beneath the epithelium is lamina propria and is rich in lymphoid cells producing IgAthat is transported across the epithelium and kills bacteria and viruses

Ciliated psuedostratified columnar epithelium of bronchi

Goblet cells with a seromucinous secretionLamina propria with lymphoid cells

Respiratory Histology

Nasal Cavity• Consists of the nasal

septum, nasal cavities, paranasal sinuses, and the nasopharynx– Paranasal sinuses act as

resonance chambers for speech

• Involved in filtering, humidifying, adjusting the temperature of inspired air

• Nasal mucosa has ciliated pseudostratifiedepithelium with goblet cells supported by lamina propria containing serous and mucous glands

Nasal cavity with sinuses

Nasal mucosa with serous and mucous glands

Respiratory Histology

Pharynx

• Divided into 2 portions:– Nasopharynx: continuous with nasal cavity with

ciliated pseudostratified columnar epithelium and goblet cells

– Oropharynx: digestive tract mucosa – stratified squamous epithelium and pure mucous glands

Respiratory Histology

Larynx• Epiglottis is a valve

like structure attached to the hyoid bone that closes the opening to the larynx during swallowing, preventing food entering the respiratory passage

• Mucosa is pseudostratifiedcolumnar

• In epiglottis & vocal cords there is stratified squamousepithelium due to wear and tear

Transition zone of pseudostratifiedcolumnar to stratified squamous at the vocal cords

Respiratory Histology

Trachea• Rigid tube containing 16-20 segments

of hyaline cartilage joined by trachealissmooth muscle

• Branches into 2 primary bronchi, one to each lung

• Subdivided into pseudostratifiedcolumnar epithelium with abundant goblet cells, a submucosa of loose C.T. with seromucinous glands and the adventitia with the cartilage, C.T. and smooth muscle

Ciliated pseudostratifiedcolumnar epithelium of trachea

Respiratory Histology

Bronchi• Primary bronchi give rise to secondary and

tertiary bronchi• Secondary bronchi supply lobes of each lung

and then divide to form the tertiary bronchi that supply the segments of each lobe, with both having:

– *Ciliated simple columnar epithelium*: start to lose stratification

– Discontinuous cartilaginous plates in their adventitia for less rigidity

• Tertiary bronchi then split into progressively smaller bronchioles, characterized by:

– Simple columnar to cuboidal epithelium– Submucosal glands disappear leaving mucosa

surrounded by loose C.T. – Goblet cells disappear– Elastic fibers increase in the lamina propria– The terminal bronchioles give rise to the

respiratory portion of the bronchial tree and feature the above characteristics particularly prominently

Discontinuous cartilaginous plates of secondary bronchus

Ciliated simple columnar epithelium of later bronchi Terminal bronchiole

Respiratory Histology

The Lungs• Paired organs in the pleural cavities

covered by visceral pleura• C.T. in the lungs is rich in elastic

fibers and smooth muscle allowing expansion– Elastic recoil important for

contraction during expiration• Right lung has three lobes; left lung

has two with each receiving the primary bronchus and the pulmonary artery at the hilus– Each lobe subdivided into

bronchopulmonary segments carrying their own blood supply and finally into lobules of pyramidal shape separated by C.T. septae

– Internal structure of the lung is a bronchial tree

• At the respiratory passages, the branches of the pulmonary artery break up into the alveolar capillaries

Bronchopulmonary segment

Pyramidal shaped lobule

Respiratory Histology

Respiratory Bronchioles• Terminal bronchioles give rise to two orders of

respiratory bronchioles that bear:– Alveolar ducts that are filled with thin-walled

outpouchings called alveoli sacs that contain hundreds of alveoli

• Sacs contain reticular and elastic fibers but no smooth muscle – Ciliated cuboidal epithelium

Cuboidal epithelium of respiratory bronchiole

Terminal portion of respiratory treeRespiratory Histology

Alveoli• Lined by simple

squamous epithelium• Intraalveolar septum

formed between adjacent alveolicomposed of C.T. of reticular and elastic fibers with anastomosing network of capillaries

• Alveolar histiocytesphagocytoseparticulate matter, bacteria, viruses that reaches the alveoli

Alveoli with capillaries

Alveolar macrophagesRespiratory Histology

Alveolar Membrane• Lined by 2 continuous cell types:

– Type I pneumocytes: squamousepithelial cells situated near the capillaries and composing the barrier through which gases pass

– Type II pneumocytes: cuboidalepithelial cells that contain a multilaminar body/cytosome that contains *surfactant* which reduces surface tension along the epithelial surface, preventing collapse during expiration

Type I and II pneumocytes

Type II pneumocyte with surfactant

Multilaminar bodyRespiratory Histology

Pneumonia• Inflammation of the lung of two major

forms:– Alveolar pneumonia

• Intraalveolar inflammation, i.e. bronchopneumonia or lobar pneumonia

– Interstitial pneumonia• Involves the alveolar septae, i.e. viral pneumonia

• May be caused by bacteria, viruses, and less commonly, by fungi, protozoa, other parasites, and aspiration

• Bacteria are the most common pathogens and account for 75%

– Most important are Streptoccocus, Staphylococcus, and Haemophilus influenzae

– Normal URT does not harbor gram negatives; but gram negatives are enteric flora and can cause pneumonia by contamination of the blood to the lungs

– Legionella infection can occur after inhalation from humidifiers or air-conditioning systems

• Viral pneumonias are acquired by close contact with infected people

• Most bacterial, viral pneumonias are acute, but if untreated, may become chronic

LG 7.8: Pathology of Pneumonias

Intra-alveolar pneumonias

Two major forms:1. Alveolar pneumonia which is marked by

intraalveolar inflammation, either as a Bronchopneumonia or Lobar pneumonia.

2. Interstitial pneumonia which primarily involves the alveolar septae, which includes viral pneumonia.

• May be caused by bacteria, viruses, and less commonly, by fungi, protozoa, other parasites, and aspiration

• Bacteria are the most common pathogens and account for 75% of pneumonias– Most important are Streptoccocus,

Staphylococcus, and Haemophilus influenzae– Normal URT does not harbor gram negatives;

but gram negatives are enteric flora and can cause pneumonia by contamination of the blood to the lungs

– Legionella infection can occur after inhalation from humidifiers or air-conditioning systems

• Viral pneumonias are acquired by close contact with infected people

• Most bacterial, viral pneumonias are acute, but if untreated, may become chronic

Alveolar Pneumonia

• Pneumonia limited to the segmental bronchi and surrounding parenchyma is called Bronchopneumonia

• Widespread or diffuse alveolar pneumonia is called Lobar Pneumonia.

Lobar pneumonia• Widespread or diffuse alveolar

pneumonia is called Lobar Pneumonia.– Often the end result of confluent

Bronchopneumonia in which the infection spreads from one lobule to another until the entire lung is involved.

– Causes a total whiteout of an entire lobe or lobes on chest X-ray.

– Dullness to percussion if there is frank consolidation or associated effusion

– Tachycardia, tachypnea and fever– Bronchial breath sounds– Increased fremitus and egophony– Blood Gas Analysis: May detect

hypoxia and even respiratory acidosis

– Streptococcus pneumoniae most common cause of Lobar pneumonia

Bronchopneumonia

• Acute inflammatory infiltrates extending from the bronchioloes into the adjacent alveoli

• Patchy distribution involving one or more lobes

• S. Aureus, H. Influenzaeand KlebsiellaPneumoniae are most common causes Intra-alveolar pneumonias

Interstitial Pneumonia• Involves the alveolar septum• Usually diffuse, often bilateral• Usually caused by viruses or mycoplasma pneumoniae• Peripheral Blood Smears: bacterial pneumonias are accompanied

by Leukocytosis (Neutrophilia), viral pneumonias are not, al-though it may be associated with a Lymphocytosis in the blood.

LG 7.8: Pathology of Pneumonias

Complications of Pneumonia

With purulent bacteria, pus fills the entire pleural cavity (pyothorax), or is encapsulated by fibrous tissue into pockets called Empyema, which occurs more commonly.

Suppurative pleuritisheals slowly and usually results in pleural fibrosis encasing the entire lung and obliterating the pleural cavity, restricting inspiration.

Suppurative Pleuritis

Purulent Pulmonary Empyema

Complications of PneumoniaAbscesses: are usually associated with virulent organisms, such as Staphylococcus, and causes destruction of the lung parenchyma and suppuration.

The pus inside the bronchi causes destruction of their walls and permanent dilatation (Bronchiectasis).

Encapsulated Pulmonary Abscess

Pulmonary AbscessBronchiectasis With Dilated Bronchi

Complications of Pneumonia

Chronic Lung Disease: an important complication caused by an unresponsiveness to treatment.

Destruction of the lung parenchyma with concomitant fibrosis transform the lung into a honeycomb-like structure

Honeycomb-Lung due to Fibrosis

Pneumococcal Pneumonia

Infection with St. pneumoniae accounts for >50% of all bacterial pneumonias and usually reach the alveoli in droplets of mucus or saliva.1. Engorgement: the first 4-12 hours. Serous exudate

pours into the alveoli from dilated, leaky blood vessels.2. Red Hepatization: The next 48 hours. The lungs

assume a red liver-like appearance, as RBC’s, fibrin, and PMN’s fill the alveoli.

3. Gray Hepatization: By 3-8 days, the lungs become grayish as the WBC’s and fibrin consolidate in the alveoli.

4. Resolution: By 7-11 days, the exudate is lysed and resorbed by macrophages, restoring the tissue to the original structure.

Pneumococcal PneumoniaEngorgement with Serous Exudate

Red Hepatization due to Congestion

Pneumococcal Pneumonia onset is typically sudden with chills, fever, pleuritic chest pain, cough and rust-colored sputum.,Lobar pneumoniaDifferentials: (Streptococcus Pneumoniae )Morphology: Gram + diplococci; “Lancet shaped”, encapsulated, Facultative anaerobeClinical diagnosis: α-hemolytic, Optochin and Bile sensitive, Quellung test -positive, catalasenegative

Grey Hepatization

Staphylococcal Pneumonia• Staphylococcus aureus pneumonia

tends to produce multiple abscesses.– Bronchpneumonia– A virulent form of pneumonia– Common in debilitated hospitalized

patients.– Common in IV drug users

• Differentials:• Morphology: Gram +,cocci,

encapsulated, protein A in the cell wall, yellow, creamy, grapelike clusters on culture

• Clinical diagnosis: Coagulase +, Catalase +, β-hemolytic, novobiocinsensitive, ferments mannitol

Pulmonary Abscess Due to Staph

Staphylococcus aureus on Gram Stain

Gram Negative Pneumonias

• Pseudomonas aeruginosa– Most common hospital-acquired

pneumonia – Vascular lesions that cause infarcts

and necrosis of the lung parenchyma– Most common cause of lung

infections in Cystic Fibrosis – Found in contaminated ventilator

equipmentDifferentials:• Morphology/Clinical diagnosis:

Gram - rod; blue-green colonies, grape like odor, mono-flagellated, Oxidase +

Mono-flagella seen on Gram stain

Gram Stain of P. aeruginosa

Gram Negative Pneumonias

• Klebsiella pneumoniae– Infection occurs in middle-aged,

alcoholic males usually through aspiration

– Lobar pneumonia– Thick currant-red jelly sputum– Necrotizes tissue forming cavitiesMorphology/Clinical diagnosis:

• Gram – rod, encapsulated, nonmotile, facultative anaerobe,Indole negative, ferments lactose

Pneumonia caused by K. pneumoniae

Atypical Pneumonia• Mycoplasma pneumoniae

(Walking pneumonia):– bacterial-like organism – Interstitial pneumonia– Fever less pronounced– Mild dry cough– Affects young adults, prisons and military bases– Only bacteria that contains cholesterol in

membrane– Smallest free living organism– Chest X-Ray often looks worse than symptoms

suggest• Morphology/Clinical diagnosis

– Not gram stainable– No cell wall instead it has a cell membrane– Nonspecific cold agglutinins– “Fried egg appearance” on culture– Serological and PCR detection

Atypical Pneumonia• Legionella pneumophila

– Legionnaires Disease (Atypical pneumonia)– Outbreak of pneumonia at an American Legion

convention in Philadelphia in 1976.– Ubiquitous in natural and man-made water

environments– Air-conditioning systems, cooling towers, and

whirlpools– Settles in the lower respiratory tract and is

engulfed by macrophages, where it replicates– Infects older smokers, alcoholics, AIDS, cancer,

and renal transplant patients– Lobar pneumonia– High fever, mental confusion, proteinuria,

hematuria– Non purulent cough– May lead to Pontiac fever (Acute flu like

symptoms)Legionnaires’ Disease-Lobar Infiltrate

Legionnaires’ Disease

Morphology/Clinical diagnosis:– Gram - rod, Gram stains poorly,– Dieterle silver stain instead– Facultative Intracellular

parasite– Catalase and oxidase positive– Produces beta lactamases– Fluorescent antibody staining– Culture on charcoal yeast

extract with iron and cysteine– Serology

Alveoli with Foamy Macrophages

Immunofluorescence Staining for Legionella Pneumophila

Atypical PneumoniaCHLAMYDIACEAE: Giemsa stain +• Chlamydophila pneumoniae :

– Transmitted person-to-person by respiratory secretions. – Infect and replicate in smooth muscle cells, endothelial cells of

the coronary artery, macrophages, etc.

– The microimmunofluorescence (MIF) test is the only acceptable test for serodiagnosis

• Chlamydophila psittaci :– Natural reservoir is any species of bird (ornithosis, parot fever) in the

blood, tissues, feces, and feathers; person-to-person transmission is rare.

– Respiratory infections: range from asymptomatic to severe bronchopneumonia with localized infiltration of inflammatory cells, necrosis, and hemorrhage.

• Chlamydia trachomatisGeneral Characteristics:

– Obligate intracellular organisms– Gram-negative bacteria; small, round-to-ovoid. – Cell envelope consists of two lipid bilayers (with LPS) but contains

NO peptidoglycan, or muramic acid– Energy parasite: Unable to synthesize ATP or regenerate NAD+

by oxidation; carry out the usual bacterial metabolic activities with host high-energy molecules.

– Elementary bodies: metabolically inactive, infectious forms

– Reticulate bodies: metabolically active, noninfectious forms

BORDETELLA PERTUSSIS AND WHOOPING COUGH

B. pertussis:– small, Gram-negative,

strictly aerobic coccobacilli– Highly sensitive to drying so

be very careful during collection or transport

– Strong tissue tropism for the ciliated epithelial cells of the respiratory tract.

– Tracheitis and bronchitis– Prevented with DTaP

vaccines: B. pertussis toxins, diphtheria and tetanus toxoids

Fungal Pneumonias

• Usually develop from inhaled spores causing granuloma formation, scarring, calcification, and cavity formation

• Are much less frequent than bacterial

Fungal Granuloma (Coin Lesion)

Histoplasmosis• Histoplasma capsulatum:

– Dimorphic fungus – In the U.S., it is endemic to central and eastern

states, especially in the Ohio and Mississippi River Valleys.

– Found in soil, bird or bat droppings (bat guano)– @25°C-Hyphae with macronidia and

microconidia-Tissue form– @37°C-Yeast inside macrophages-Intracellular

form– The inhaled spores, called Microconidia, are

engulfed by macrophages and develop into yeast forms inside the lungs.

– Oval, budding yeasts inside the macrophages, spread widely throughout the body, especially to the liver and spleen

– Yeast cells are round and has a central basophilic body surrounded by a clear halo

– Best identified by silver stains.– Chronic infection in immunocompromised

individuals leads to hepatosplenomegaly. – Symptoms: flu-like, weight loss and night sweats

resemble TB.

Hyphae with Macronidia

Histoplasma PneumoniaYeast within Macrophages

Cryptococcus neoformans• Cryptococcus neoformans:

– Systemic, opportunistic mycosis, which affects the meninges and the lungs.

– Oval, budding yeast surrounded by a wide polysaccharide capsule that may be used for diagnosis.

– India Ink Prep for diagnosis.– Urease Postive– Latex agglutination test for capsular

antigens in blood– “Soap Bubble lesions” Mucoid clear

capsules– The main reservoir is pigeon droppings in

the soil, but the birds are not affected.– Occurs almost exclusively in persons with

impaired cell-mediated immunity, especially AIDS, leukemia and lymphoma patients

Cryptococcal Pneumonia with Mucoid (clear) Capsules

Mucicarmine Stain for the Capsules of Cryptococcus

Aspergillus fumigatus• Aspergillus fumigatus:

– Saprophytes in soil and decaying plant matter, and are small enough to reach the alveoli

– Septate hyphae that forms V-shaped branches at 45 degrees, Rhizopus Mucorhas a branches at 90 degrees

– It can colonize and also invade abraded skin, wounds, burns, cornea, or paranasalsinuses.

– Immunocompromised patients, where it can invade the lungs and other organs, producing hemoptysis and granulomas.

– It can also grow within pulmonary cavities from TB and produce an “Aspergilloma” (fungal ball) with can be seen on X-Ray, along with cavatation.

Aspergillus-RUL Cavitation

V-shape branch, septatedhyphae

Coccidioides immitis Pneumonia• Coccidioides immitis

– Chronic, necrotizing infection that resembles Tuberculosis, and is endemic to arid regions of Southwestern U.S. and Latin America.

– Particularly common in the San Joaquin Valley of California (“Valley Fever”)

– @25°C-Arthroconidia– @37°C-Sperules in endospores– In soil, it forms hyphae with Arthrospores– Arthrospores form Spherules that are large

vacuoles with a thick wall that are filled with Endospores.

– Upon rupture of the walls, the endospores are released and differentiate to form new spherules, to spread either via the blood or by direct extension, forming caseating granulomas, similar to T.B.

– Considered one of the most contagious organism when grown in the laboratory

Ruptured Spherules

Cylindrical anthrocondia

Pneumocystis JiroveciPneumocystis Jiroveci/carinii:

– An important cause of diffuse interstitial pneumonia in immunocompromisedpatients

– Has characteristics of both a fungus and a protozoan parasite

– Causes pneumonia in AIDS patients. (frequently the first diagnosed opportunistic infection and the leading cause of death).

– Appears as dark ovoid sporozoites within cysts on Silver stain

– Frothy, eosinophilic, edema fluid that blocks oxygen exchange.

– CXR reveals a diffuse interstitial pneumonia

– Does NOT contain ergosterol in cell membrane.

– Can NOT be cultivated, diagnosis rely on microscopic examination.

– GMS Silver Stain

Pneumocystis carinii Silver Stain

Blastomyces dermatitidis

• Blastomyces dermatitidis:• Mostly in South Central and

South Eastern US• Characteristic hyphae and

microconidia• @27°C-Hyphae with small

conidia• @37°C-Budding yeast with broad

base in tissue• Primary lung infection is limited

in most individuals.• Prognosis poor;most severe

mycoses• Lung lesions do not calcify

Blastomyces dermatitidis hyphae

Giemsa stain of B. dermatitidisshowing broad-based budding yeast

Viral PneumoniaRespiratory Syncytial Virus (RSV):– Is the most common cause of upper and lower RTI in infants/young children

Influenza:– Is caused by influenza viruses types A and B (but not C)

transmitted by airborne droplets.– Antigenic Shift occurs only in Type A virus because of its

unique presence in other animal species– Common cold, pharyngitis, tracheobronchitis, and

bronchiolitis or croup in children.– Enveloped; -, ssRNA

– Hemagglutinin and neuraminidase are major surface antigens for Subtyping.

– Serotyping is based on the M and NP proteins

– Synthesis of viral mRNA and RNA genome occurs in nucleus

Sarcoidosis• Most common in black women • Unknown etiology • CD-4 positive T-helper

lymphocytes increased in lung, but decreased in circulation

• The lungs, lymph nodes of the thorax and neck, and the liver are most often involved.

• Non-caseating granulomas, which can involve any organ

• Granulomas of the lacrimalglands and salivary glands are found in one-third of patients. Noncaseating Granulomas with

Multinucleated Giant Cells

• Granulomas are distributed around bronchi, bronchioles and blood vessels, alveoli

• Asteroid Bodies (star-shaped crystals) and Schaumann Bodies (calcified lamellar structures) may be seen in granulomas.

• There is a tendency for the lesions to heal with pulmonary fibrosis and hyalinization.

• Hepato-splenomegaly occurs in about three-fourths of cases

• Subcutaneous nodules to erythematous plaques, similar to Lupus.

• Iritis, uvitis, blurry vision and possible blindness

• Low-grade fever, feeling tired, anorexic, dyspnea, cough, or wheezing

Asteroid Body in Sarcoidosis

Schaumann Body within Giant Cell

• X-ray studies show pulmonary nodules (“Potato nodes”) and hilarlymph node involvement.

• Increased Angiotensin-Converting Enzyme (ACE), which is released from macrophages in granulomas.

• Hypercalcemia related to elevated levels of active Vitamin D, released from macrophages in the granulomas.

• Treatment: Corticosteroid therapy

Hilar Lymphadenopathy

CT-Hilar Lymphadenopathy Plaque-Like Skin Lesions

Cutaneous Sarcoidosis

Tuberculosis• Chronic bacterial infectious

disease; mycobacterium tuberculosis– Rod-shaped, waxy capusle

– Acid fast (Mycolic acid)

– Obligate aerobe

– Multiply within alveoli

• Does not attract PMNsGranulomas with caseous

necrosis and Giant cells

Multi-Nucleated Giant Cells

TB-Acid-Fast Stain

TB Infection Stages• Primary

– Initial infection usually occurs in the lower lobes – Ghon Complex

– Consist of a calcified focus of infection and an associated lymph nodes– Ghon nodule is well circumscribed with central necrosis.– In later stages, the lesion is fibrotic and calcified

– Usually forms calcified granulmatous lesion.– Primary infections are asymptomatic– Can spread to other parts of lung in children and immunocompromised called

“progressive primary tuberculosis”– Necrotic central liquefaction

• Secondary– Reactivation of dormant primary infection– Bacteria spread to apex and upper lobes of lungs– Cavities form causing hemoptysis– Miliary Spread to well oxygenated organs.

• Contralateral pneumonia• Pleuritis• TB laryngitis• Intestinal TB• TB menigitis• Spread to spine ( Pott’s Disease)

Clinical Features of TB

• Non Specific: Fever, fatigue, night sweats, weight loss

• Secondary TB– Non-productive dry cough– Low grade fever– Loss of appetite, weight loss– Hemoptysis

• Miliary Spread– Scrofula is a unilateral cervical

adenitis that presents with swollen non-tender nodes.

Primary Ghon Complex of Tuberculosis

Spread of Tuberculosis to Lower Lobe

TB Skin Test

PPD (purified protein derivative)– 5-9mm is a positive test.

• BCG immunization can cause wheal 5-10mm but decrease with passage of time

• Cultured on special media (Lowenstein-Jensen Agar

• Treatment:– Isoniazid (6 months),

Rifampin (6 months), Pyrazindamide (2 months)

Pott’s Disease

Miliary Tuberculosis

Asthma• Definition: bronchial

hyperresponsiveness causes reversible bronchoconstriction

• Extrinsic asthma (type I hypersensitivity reaction with exposure to extrinsic allergens)– Allergic (atopic)

• Most common type• Children with an atopic family

history– Occupational exposure: fumes,

gases, and chemicals• Intrinsic asthma (unknown

mechanism)– Nonimmune– Can be triggered by viral URI’s,

stress, exercise, drugs (aspirin)

• Clinical Findings:

• Episodic expiratory wheezing

• Noctural cough

• Dyspnea

• Tachypnea

• Hypoxemia

• Pulsus paradoxus

• Increased anteroposteriordiameter

• Mucus plugging

Histology of Asthma• Spiral-shaped mucus plugs• Hypertrophy of mucus glands

with goblet cell hyperplasia• Smooth muscle hypertrophy• Thickened basement

membranes• Inflammation (especially with

eosinophils)

Basement membrane thickening

Mucus plug

Goblet cell hyperplasia and smooth muscle hyperplasia

Sputum cytology of Asthma

• Curschmann spirals: twisted mucous plugs admixed with sloughed shed bronchial epithelium

• Inflammation (especially with eosinophils)

• Charcot-Leyden crystals: composed of eosinophilmembrane protein

Curschmann spirals

Eosinophils

Chronic Bronchitis• Clinical diagnosis:

productive cough for at least 3 months for 2 consecutive years

• Causes– Smoking cigarettes (most

common)– Cystic fibrosis

• Pathogenesis– Hypertrophy of mucus-

secreting glands in the bronchioles -> Reid index = gland depth / total thickness of bronchial wall; in COPD, Reid index > 50%

• Clinical Findings– Productive cough– Dyspnea– Expiratory wheezing– Crackles– Frequent infections– Cyanosis

• Patients are called “blue bloaters”

– Cor pulmonale is commonly present

Microscopic Features of Chronic Bronchitis

• Hypertrophy of bronchial mucus glands -> sputum overproduction

• Goblet cell metaplasia

• Chronic inflammation and fibrosis narrowing the lumen

• Loss of ciliated epithelium and presence of squamous metaplasia(smokers)Squamous metaplasia

Adult Respiratory Distress Syndrome

Definition: transudation into the lungs at normal wedge pressures resulting in bilateral infiltrates and a widened A-a gradient > 200.

ARDS – Precipitating CausesDirect IndirectPneumonia ** Acute pancreatitis-aspiration Liver Failure-toxic inhalation Sepsis***-near drowning Toxic ingestionPulmonary Contusion EmbolismExudative phase Acute phase

– Loss of barrier function pulmonary edema– Increased pulmonary vascular resistance– Alveolar collapse from surfactant abnormalities– V / Q mismatch

Proliferative Phase• Fibrosis and honeycombing

Acute phase: the bilateral alveolar opacities are denser in the dependent, posterior lung zones, with sparing of the anterior lung fields. The arrows indicate thickened

interlobular septa, consistent with the presence of pulmonary edema. A CT scan of the chest obtained during the fibrosing-alveolitis phase. There are reticular opacities and diffuse ground-glass opacities throughout both lung fields and a large bulla is present

in the left anterior hemithorax.

55Talk ARDS

ARDS – Treatment

PEEP ( Positive End Expiratory Pressure)– recruit alveoli and

prevent collapse of others

– each 5 cms of PEEP increases the functional residual capacity (FRC) by 250 cc and decreases shunt.

Hyaline membrane found in ARDS

• Obstructive sleep apnea – Excessive snoring with intervals of breath cessation (called apnea) – Causes

• Obesity (very common) – Pharyngeal muscles collapse due to the weight of tissue in the neck.

• Tonsillar hypertrophy, nasal septum deviation

• Pathogenesis – Airway obstruction causes CO2 retention, leading to hypoxemia.

• Clinical findings – Excessive snoring with episodes of apnea – Daytime somnolence often simulating narcolepsy

• Laboratory findings – Decreased PO2 and O2 saturation during apneic episodes – Increase in arterial PCO2 (respiratory acidosis)

• Complications – Pulmonary hypertension (PH) leading to right ventricular hypertrophy

• Called cor pulmonale (see section VII) – Secondary polycythemia

• Due to a hypoxemic stimulus for erythropoietin release

• Polysomnography– Confirmatory test that documents periods of apnea during sleep

• Treatment – Nasal continuous positive airway pressure (CPAP) – Surgical correction of any obstructive lesions, weight loss

Pulmonary thromboembolism:Source

• Majority (95%) originate in the femoral vein – Risk factors for thromboembolism

• Stasis of blood flow (e.g., prolonged bed rest), hypercoagulable states

Red-blue, raised, wedge-shaped area that extends to the pleural surface– Pleural surface has a fibrinous exudate (produces a pleural friction rub).

• Hemorrhagic pleural effusion may also occur. – Majority are located in the lower lobes.

• Perfusion is greater than ventilation in the lower lobes.

Clinical findings – Saddle embolus

• Sudden increase in pulmonary artery pressure • Produces acute right ventricular strain and sudden death

– Pulmonary infarction • Sudden onset of dyspnea and tachypnea• Fever • Pleuritic chest pain (pain on inspiration), friction rub, effusion

Laboratory findings with a pulmonary infarction – Respiratory alkalosis (arterial PCO2 <33 mm Hg) – PaO2 less than 80 mm Hg (90% of cases) – Increase in A-a gradient (100% of cases) – Abnormal perfusion radionuclide scan

• Ventilation scan is normal, but the perfusion scan is abnormal. • Pulmonary angiogram is gold standard confirmatory test.

– Positive D-dimers• Negative D-dimer + negative ultrasound essentially rules out DVT• If elevated proceed with CTA or rarely MRA• Initial Chest X-Ray almost always normal

Plain film radiography Chest X-ray• Initial CxR always NORMAL.

• May show – Collapse, consolidation, small pleural effusion, elevated diaphragm.

Westermark sign Dilatation of pulmonary vessels proximal to embolism along with collapse of distal vessels, often with a sharp cut off; Dark spot surrounded by opacities.

Pleural based opacities with convex medial margins are also known as a Hampton's Hump

Emphysema• Definition:

a form of COPD characterized by enlarged airspaces and destruction of the respiratory unit: respiratory bronchioles, alveolar duct, alveoli

• Pathogenesis in smokers :CentrilobularEmphysema: smoke irritants are attract inflammatory cellsreleaseelastasedestruction of alveolar wallcreation of alveolar spaces

• Panacinar Emphysema: accounts for 1% of emphysema cases. Autosomal recessive disorder . Patients lack the alpha-1-antitrypsin serum protein a.k.a anti-protease made in the liver, therefore they are defenseless against proteases produced by bacteria, PMN’s, monocytes, macrophagesresults in destruction of elastin/reticular fibers in the lung- lose elastic recoilgeneral distension and enlarged alveolar spaces Bullae formation

Bullae Formation

Bullous Formation

EmphysemaPathology: Lungs appear enlarged/whiter/filled with Blebs and Bullae. Lungs do not collapse, however.

1. Centrilobular emphysema-Think smokers & involves the upper lobe respiratory bronchioles are permanently disteneded. Alveoli are spared

2. Panacinar emphysema: think non-smokers with a genetic defect. Involves all airspaces distal to the terminal bronchioles and alveoli are permanently distended

Centrilobular Emphysema

Panacinar Emphysema

Emphysema w/ Subpleural Blebs

Clinical features of EmphysemaCXR-Emphysema-Increased Interstitial Markings and Flattened Diaphragm

Emphysema “Pink Puffer”

Clinical Feature of Emphysema

• No bronchial obstruction No irritation coughing is not a symptom (more so in chronic bronchitis)

• Compensatory tachypnea & the chest is over-expanded “barrel-shaped”

• Onset of dyspnea: progressive, constant, severe• Appearance: “Pink puffers” (not cyanotic because

they are hyperventilating so blood is oxygenated) & thin in a hunched over position

• Chest X ray: Clear lung fields with over inflation

Chronic Bronchitis Versus Emphysema

Cystic Fibrosis• Autosomal recessive disease 1 in 2500 neonates in the U.S.

affects caucasians CF gene codes for a Chloride Transport channel responsible for glandular NaCl/H2O secretions from all exocrine glands (pancreas, intestines, bronchi) results in hyperviscous mucous production/obstruction development of viscous plugs which prevent respiration mucous is susceptible to bacterial growth patients are vulnerable to chronic bronchitis, pneumonia, and bronchiectasis

CXR-Cystic Fibrosis with Bronchiectasis

Lung CT-Cystic FibrosisBronchiectasis

Clinical features of Cystic fibrosis • Higher than normal amounts of salt (sodium chloride) in their sweat. This

may be one of the first signs parents notice because they can taste the salt when they kiss their child. Physician can use the Sweat test to diagnose

• Blockage in the bowels.• Foul-smelling, greasy stools.• Delayed growth.• Thick sputum. It's easy for parents to overlook this sign because young

children tend to swallow their sputum rather than cough it up.• Coughing or wheezing.• Frequent chest and sinus infections with recurring pneumonia or

bronchitis.• Protrusion of part of the rectum through the anus (rectal prolapse). This is

often caused by stools that are difficult to pass or by frequent coughing.• Enlargement or rounding (clubbing) of the fingertips and toes. Although

clubbing eventually occurs in most people with cystic fibrosis, it also occurs in some people born with heart disease and other types of lung problems.

• CYSTIC FIBROSIS IS INCURABLE & MOST PATIENTS DIE IN THEIR 20’S AND 30’S DUE TO PULMONARY INFECTIONS….LIFE MAY ME PROLONGED WITH TREATMENT OF INFECTIONS AND CORRECTION OF NUTRITIONAL DEFICIENCIES

Bronchiectasis• Permanent dilatation of the bronchi most

common complication of chronic bronchitis mucopurulent material fills the dilated bronchi/bronchioles & cannot be cleared with coughing infection results and spreads to adjacent alveoli recurrent pneumonias are common with hematogenic spread of infection to other organs

Bronchiectasis

ADHESIONS-

Mucus- Filled Bronchioles

Dilated Bronchioles

Pediatric Dyspnea

• StridorLevel of obstruction

• Inspiratory Above the cords (extrathoracic); e.g. croup, epiglottitis

• Expiratory Below the cords (intrathoracic); e.g. foreign body

• Biphasic At or below the cords (intra or extrathoracic); e.g.

• Foreign body, bacterial tracheitis

Croup AP Neck ‘Steeple chase’sign in 40-50%

Lung Tumors• Pulmonary Hamartoma

– A malformation that may be classified as a true tumor, that typically occurs in adults

– Grossly they appear as solitary, circumscribed lobulated masses with a white or gray cartilaginous cut surface, averaging about 2 cm in diameter.

– The cause of about 10% of “coin lesions” discovered incidentally on chest X-ray.

– The tumor is benign and well-circumscribed – Most occur peripherally

Carcinoma of the Lung-Etiology• Most cases of bronchial cancer is associated with preneoplastic lesions.• Small cell and squamous cell carcinomas are typically centrally located• The sequence of events begins as a metaplasia of the bronchial epithelium, a benign,

reactive lesion characterized by a transformation of normal, pseudostratified columnar epithelium into a stratified squamous epithelium, and initially, is a reversible lesion.

• Tumors of neuroendocrine cells are called “Small or Oat-Cell Carcinomas”• If the transformation of deeper, stem cells progresses and become anaplastic, the tumor

will be histologically classified as an “Undifferentiated Large Cell Carcinoma”, because these cells became anaplastic before differentiation.

• Bronchial tumors composed of ciliated and mucous cells, resembling the normal cells in the bronchus, tend to form irregular glands and are classified as “Adenocarcinomas”.

• Such tumors can also grow inside the alveoli and are called BronchioloalveolarCarcinomas.

• Any of the four types of lung tumors can be centrally located, but can also be peripherally located, most of these are Adenocarcinomas

• Peripheral Adenocarcinomas may also originate from pulmonary scars, probably from bronchiolar cells trapped in fibrous tissue.

• Tumor in the Apex of the Lung is called a Pancoast tumor, which can impinge the sympathetic chain and lead to Horner’s syndrome: Ptsosis, myosis anhydrosis

Squamous Cell Carcinomas• These tumors produce cough, dyspnea, hemoptysis, chest pain and

possibly a pneumonia with pleural effusions Most arise in the central portion of the lung

• Grossly, the are firm, gray-white ulcerative masses which extend through the bronchial wall into the adjacent parenchyma

• Central cavitation is frequent• On cut section there is hemorrhage and necrosis• Microscopic appearance is variable

– Well differentiated tumors have keratin production (pearls) which consists of small round nests of eosinophilic aggregates of keratin surrounded by concentric layers of squamous cells.

– Intracellular bridges between the squamous cells and well formed but malignant invasive nests and islands of squamous cells

– poorly-differentiated tumors exhibit no keratinization and the tumor is difficult to determine if the tissue is squamous or some other cell type (undifferentiated).

– Tumor cells may be readily found in the sputum and the diagnosis may be made by cytology from bronchial washings or bronchial brushings during bronchoscopy. (central location)

– They tend to metastasize to local lymph nodes (hilar) and somewhat later, so the life expectancy is a little better than the other cell types.

Cytology-Squamous Carcinoma

Intracellular Bridges Between Malignant Squamous Cells

Nests of W.D. Squamous Cell Carcinoma with Intracellular Bridges

Squamous Carcinoma with Keratin

Adenocarcinoma of the Lung• 3 P’s: Pleural, periphery of the lung and puckering• Associated with K-ras oncogene• Forms granule spaces, which is seen on microscopy• Tend to arise in the periphery of the lungs, and often associated with scars which

can result in puckering of the pleural• Central tumors have endobronchial growth and tend to invade bronchial cartilage• Appear as irregular masses, which on cut section appear gray-white in color, soft

and glistening, depending on the amount of mucus produced• There are four different subtypes of Adenocarcinoma histologically, acinar,

papillary, solid with mucus formation, and bronchioloalveolar– Acinar type, and when well-differentiated, form regular glandular structures, lined by

neoplastic cuboidal cells, filled with mucus.– Papillary type has neoplastic cells resting on a fibrovascular connective tissue core.– Mucus production occurs in only half of Adeno-carcinomas– Intracellular mucus stained with a PAS or Mucicarmine stain– Bronchioloalveolar Carcinoma

– grows along preexisting alveolar walls– 2/3 are nonmucinous– Doesn’t destroy septae, grows along walls of preexisting

alveoli– Columnar in appearance

Acinar Type Adenocarcinoma

Papillary Adenocarcinoma

Mucicarmine Stain for Mucin

Bronchioloalveolar Carcinoma-CT

Bronchioloalveolar Carcinoma

Peripheral Adenocarcinoma-CXR

Granule-like spaces

Granule-like spaces

Mucin rich gray white nodules

Small Cell Carcinoma• Highly malignant epithelial tumor that exhibits

neuroendocrine features• Central mass• The male to female ratio is about 2:1• The tumor grows and metastasizes rapidly, and 70%

of pt’s have advanced disease at diagnosis• Produces a variety of Paraneoplastic Syndromes

which are distinctive for small cell, including Diabetes Insipidus, due to ADH production, ectopic ACTH (corticotropin) or Parathormone production

• Paraneoplastic syndromes: Cushing like syndrome,Lambert-Eaton myasthenic syndrome

• Appears as a perihilar (central) mass, frequently with extensive lymph node metastases

• Histologically, they consist of sheets of small, round, oval or spindle-shaped cells

• By EM, many of the cells contain secretoryneuroendocrine granules (helps in the diagnosis)

• This type of lung cancer is the only tumor that is sensitive to chemotherapy and radiation therapy

• Associated with L-myc oncogene

EM-Neurosecretory Granules

Large Cell Carcinoma

• Diagnosis of exclusion in a poorly undifferentiated non-small cell carcinoma that does not show features of squamous or glandular differentiation

• The cells are large and irregular and exhibit ample cytoplasm. The nuclei frequently show prominent nucleoli and vesicular chromatin

Carcinoid Tumor• A group of neuroendocrine neoplasms derived from the basal cells of the

bronchial epithelium• Resembles a small cell carcinoma• The large majority are endocrinologically silent• A small subset of cases is associated with an endocrinopathy, such as

Cushing syndrome– This type of Cushing syndrome is due to ectopic corticotropin production by

tumor cells• Central Carcinoid tumors are found inside the bronchioles with a fleshy,

polypoid mass that protrudes into the lumen• Uniform cytological features, consisting of eosinophilic, finely granular

cytoplasm with round, uniform nuclei, all in various patterns of growth, embedded in a vascular stroma.

• the vast majority are discovered because of a mass on CXR, and over half of these patients are asymptomatic

• The most common manifestations are hemoptysis and dyspnea

Carcinoid Lung Cancer

Malignant Mesothelioma• 80% of patients have exposure to Asbestos from

shipyards, old buildings, or brake and clutch linings• Latency period between exposure and the

appearance of the tumor is about 20-30 years• Pleural mesotheliomas encases and compresses

the lung, extending into interlobar fissures. (old terminiology: Rind Tumor)

• Invasion of the pulmonary parenchyma is generally limited to the periphery adjacent to the tumor, usually sparing the lymph nodes

• Histologically, they exhibits a biphasic appearance with both epithelial and sarcomatous patterns

• Pt’s are first seen with a pleural effusion or a pleural mass, chest pain along with weight loss and malaise

• Tends to spread locally within the chest cavity, invading, encassing and compressing structures

EM: Thin microvilli

Biphasic Pattern in Mesothelioma

Metastatic Tumors

• The most common malignant tumor of the lung is metastatic tumors

• Metastatic tumors to the lungs are usually mult-ipleand radiographically these nodules, if large enough, are called “cannon ball” metastasis

• Usual sites being the pancreas or stomach, but can be from any place.

Metastatic Pancreatic Cancer to Lung (Cannon Ball Mets)

Metastatic Colon Carcinoma

Mediastinal masses • Cough is the most common symptom (75% of cases).

– Dyspnea, hemoptysis, weight loss, chest pain – Laryngeal nerve involvement: Hoarsness– Esophageal obstruction: Dysphagia– Phrenic nerve involvement: Diaphragmatic paralysis– Pancoast tumor (superior sulcus tumor)

• Usually a primary squamous cancer located at the extreme apex of lung • Destruction of superior cervical sympathetic ganglion produces Horner's syndrome

– Ipsilateral lid lag – Miosis (pinpoint pupil) – Ipsilateral anhydrosis (lack of sweating)

– Superior vena cava syndrome • Distended head and neck veins• Plethora; redness• Facial and upper arm edema

– Paraneoplastic syndromes – Digital clubbing

• Due to reactive periosteal changes in the underlying bone – Muscle weakness (Eaton-Lambert syndrome) – Ectopic hormone secretion

• Small cell carcinoma– ACTH Cushing syndrome– ADH SIADH

• Squamous cell carcinoma– PTH Hypercalcemia

• Epidemiology – Usually metastatic primary lung cancer in older patients – Usually primary disease in younger patients – Anterior compartment is the most common site. – Most common primary mediastinal masses, in descending order:

• Neurogenic tumors – Usually malignant in children and benign in adults

• Thymomas (see below) • Primary cysts

– Usually a pericardial cyst • Malignant lymphomas

– Usually nodular sclerosing Hodgkin's lymphoma in a woman • Teratoma

• Thymoma– Epidemiology

• Located in the anterior mediastinum• Benign (70%), malignant (30%)

– Epithelium, not lymphoid tissue, is the neoplastic component. – Majority express systemic symptoms of myasthenia gravis

• Less than 10% to 15% of myasthenia patients have a thymoma. • Majority (65-75%) have follicular B cell hyperplasia in the thymus.

– Site for synthesis of antiacetylcholine receptor antibodies

– Other thymoma associations • Hypogammaglobulinemia, pure RBC aplasia• Increased incidence of autoimmune disease (e.g. Graves' disease)

Pleural EffusionCauses of pleural effusion:

– Increased hydrostatic pressure in the visceral pleura (e.g., congestive heart failure)

– Decreased oncotic pressure (e.g., nephrotic syndrome) – Obstruction of lymphatic drainage from the visceral pleura (e.g., lung cancer) – Increased vessel permeability of visceral pleural capillaries (e.g., infarction) – Metastasis to the pleura (e.g., metastatic breast cancer)

• Types of pleural effusions: • Transudates

– Ultrafiltrate of plasma involving disturbances in Starling pressures – Example-increased hydrostatic pressure or decreased oncotic pressure

• Exudates – Protein-rich and cell-rich fluid

• Due to an increase in vessel permeability in acute inflammation – Examples-pneumonia, infarction, metastasis

• Laboratory findings distinguishing exudates from transudates– Pleural fluid protein/serum protein ratio above 0.5

• Indicates an exudate• Transudates have values below 0.5.

– Pleural fluid lactate dehydrogenases/serum lactate dehydrogenase ratio above 0.6

• Indicates an exudate• Transudates have values below 0.6.