LUNG Diseases

Function of the Respiratory System
Slide 13.2
Oversees gas exchanges (oxygen and carbon dioxide) between the blood and external environment
Exchange of gasses takes place within the lungs in the alveoli(only site of gas exchange, other structures passageways
Passageways to the lungs purify, warm, and humidify the incoming air
Shares responsibility with cardiovascular system

Bronchi
Bronchioles
Terminal bronchioles
Alveolar ducts
Alveoli
Type 1 pneumocytes
Type 2 pneumocytes
Macrophages
Capillaries

N
O
R
M
A
L
C
X
R

ATELECTASIS
INCOMPLETE EXPANSION
COLLAPSE

PULMONARY EDEMA
IN-creased venous pressure
DE-creased oncotic pressure
Lymphatic obstruction
Alveolar injury

ARDS

ACUTE INTERSTITIAL PNEUMONIA
Think of it as ARDS with NO known etiology!

OBSTRUCTION v. RESTRICTION
OBSTRUCTION
Air or blood?
Large or small?
Inspiration or Expiration?
Obstruction is SMALL AIRWAY EXPIRATION obstruction, i.e., wheezing
HYPEREXPANSION on CXR
RESTRICTION
“Compliance”
“Infiltrative”
REDUCED lung VOLUME, DYSPNEA, CYANOSIS
REDUCED GAS TRANSFER
“GROUND GLASS” on CXR

OBSTRUCTION (cOPD)
EMPHYSEMA (almost always chronic)
CHRONIC BRONCHITIS? emphysema
ASTHMA
BRONCHIECTASIS

EMPHYSEMA
COPD, or “END-STAGE” lung disease
Centri-acinar, Pan-acinar, Paraseptal, Irregular
Like cirrhosis, thought of as END-STAGE of multiple chronic small airway obstructive etiologies
NON-specific
IN-creased crepitance, BULLAE (BLEBS)
Clinically linked to recurrent pneumonias, and progressive failure

CENTRO-acinar
PAN-acinar
EMPHYSEMA

Bullae, or “peripheral blebs” are hallmarks of chronic obstructive lung disease, COPD.

CHRONIC BRONCHITIS
INHALANTS, POLLUTION, CIGARETTES
CHRONIC COUGH
CAN OFTEN PROGRESS TO EMPHYSEMA
MUCUS hypersecretion, early, i.e. goblet cell increase
CHRONIC bronchial inflammatory infiltrate

ASTHMA
Similar to chronic bronchitis but:
Wheezing is hallmark (bronchospasm, i.e. “wheezing”)
STRONG allergic role, i.e., eosinophils, IgE, allergens
Often starting in CHILDHOOD
ATOPIC (allergic) or NON-ATOPIC (infection)
Chronic small airway obstruction and infection
1) Mucus hypersecretion with plugging, 2) lymphocytes/eosinophils, 3) lumen narrowing, 4) smooth muscle hypertrophy

Bronchial Asthma
Chronic inflammatory disorder of the airways resulting in contraction of bronchial muscle
Types
Extrinsic (atopic, allergic).
Allergens: food, pollen, dust, etc.
Intrinsic (non-atopic)
Initiated by infections, drugs, pollutants, chemical irritants
ATOPIC ASTHMA

Note the heavy inflammatory cell infiltrate around bronchioles and small bronchi.

What are the 4 classical histologic findings in bronchial asthma?

BRONCHIECTASIS
DILATATION of the BRONCHUS, associated with, often, necrotizing inflammation
CONGENITAL
TB, other bacteria, many viruses
BRONCHIAL OBSTRUCTION (i.e., LARGE AIRWAY, NOT SMALL AIRWAY)
Rheumatoid Arthritis, SLE, IBD (Inflammatory Bowel Disease)

BRONCHIECTASIS

RESTRICTIVE
(INFILTRATIVE)
REDUCED COMPLIANCE, reduced gas exchange)
Are also DIFFUSE
HETEROGENEOUS
FIBROSING
GRANULOMATOUS
EOSINOPHILIC
SMOKING RELATED
PAP (Pulmonary Alveolar Proteinosis

FIBROSING
“IDIOPATHIC” PULMONARY FIBROSIS (IPF)
NONSPECIFIC INTERSTITIAL FIBROSIS
“CRYPTOGENIC” ORGANIZING PNEUMONIA
“COLLAGEN” VASCULAR DISEASES
PNEUMOCONIOSES
DRUG REACTIONS
RADIATION CHANGES

IPF (UIP)
IDIOPATHIC, i.e., not from any usual caused, like lupus, scleroderma
FIBROSIS

NON-SPECIFIC INTERSTITIAL PNEUMONIA
WASTEBASKET DIAGNOSIS, of ANY pneumonia (pneumonitis) of any known or unknown etiology
FIBROSIS
CELLULAR INFILTRATE (LYMPHS & PLASMA CELLS)

CRYPTOGENIC ORGANIZING PNEUMONIA (COP)
IDIOPATHIC
“BRONCHIOLITIS OBLITERANS”

“COLLAGEN” VASCULAR DISEASES
Rheumatoid Arthritis
SLE (“Lupus”)
Progressive Systemic Sclerosis (Scleroderma)

PNEUMOCONIOSES
“OCCUPATIONAL”
“COAL MINERS LUNG”
DUST OR CHEMICALS OR ORGANIC MATERIALS
Coal (anthracosis)
Silica
Asbestos
Be, FeO, BaSO4, CHEMO
HAY, FLAX, BAGASSE, INSECTICIDES, etc.

Coal, “bagasse”, asbestos, silica nodules, and asbestos, going clockwise.

GRANULOMATOUS
SARCOIDOSIS, i.e., NON-caseating granulomas (IDIOPATHIC)
HYPERSENSITIVITY (DUSTS, bacteria, fungi, Farmer’s Lung, Pigeon Breeder’s Lung)

SARCOIDOSIS
Mainly LUNG, but eye, skin or ANYWHERE
UNKNOWN ETIOLOGY
IMMUNE, GENETIC factors
F>>M
B>>W
YOUNG ADULT BLACK WOMEN

NON-Caseating Granulomas are the RULE
“Asteroid” bodies within these granulomas are virtually diagnostic

SMOKING RELATED
DIP (Desquamative Interstitial Pneumonia)
M>>F
CIGARETTES
100% Survival
Alveolar Macrophages

Pulmonary tuberculosis
Caused by Mycobacterium tuberculosis.
Transmitted through inhalation of infected droplets
Primary
Single granuloma within parenchyma and hilar lymph nodes (Ghon complex).
Infection does not progress (most common).
Progressive primary pneumonia
Miliary dissemination (blood stream).

Pulmonary tuberculosis
Secondary
Infection (mostly through reactivation) in a previously sensitized individual.
Pathology
Cavitary fibrocaseous lesions
Bronchopneumonia
Miliary TB
Miliary
Granuloma
Fibrocaseous
Mycobacterium

VASCULAR PULMONARY DISEASES
PULMONARY EMBOLISM (with or usually WITHOUT infarction)
PULMONARY HYPERTENSION, leading to cor pulmonale
HEMORRHAGIC SYNDROMES
GOODPASTURE SYNDROME
HEMOSIDEROSIS, idiopathic
WEGENER GRANULOMATOSIS

P.E.
Usually secondary to debilitated states with immobilization, or following surgery
Usually deep leg and deep pelvic veins (DVT), NOT superficial veins
Follows Virchow’s triad, i.e., 1) flow problems, 2) endothelial disruption, 3) hypercoagulabilty
Usually do NOT infarct, usually ventilate
When they DO infarct, the infarct is hemorrhagic
Decreased PO2, acute chest pain, V/Q MIS-match
DX: Chest CT, V/Q scan, angiogram
RX: short term heparin, then long term coumadin

GROSS “saddle” embolism

PULMONARY HYPERTENSION
COPD, C”I”PD (vicious cycle)
CHD (Congenital HD, increased left atrial pressure)
Recurrent PEs
Autoimmune, e.g., PSS (Scleroderma), i.e., fibrotic pulmonary vasculature

VERY thickened arteriole in pulmonary hypertension
NORMAL pulmonary arteriole

CHF, CHRONIC
IDIOPATHIC
PULMONARY
HEMOSIDEROSIS

PNEUMONIA

PULMONARY INFECTIONS
COMMUNITY-ACQUIRED BACTERIAL ACUTE PNEUMONIAS
Streptococcus Pneumoniae
Haemophilus Influenzae
Moraxella Catarrhalis
Staphylococcus Aureus
Klebsiella Pneumoniae
Pseudomonas Aeruginosa
Legionella Pneumophila
COMMUNITY-ACQUIRED ATYPICAL (VIRAL AND MYCOPLASMAL) PNEUMONIAS
Morphology.
Clinical Course.
Influenza Infections
Severe Acute Respiratory Syndrome (SARS)
NOSOCOMIAL PNEUMONIA
ASPIRATION PNEUMONIA
LUNG ABSCESS
Etiology and Pathogenesis.
CHRONIC PNEUMONIA
Histoplasmosis, Morphology
Blastomycosis, Morphology
Coccidioidomycosis, Morphology
PNEUMONIA IN THE IMMUNOCOMPROMISED HOST
PULMONARY DISEASE IN HUMAN IMMUNODEFICIENCY VIRUS INFECTION

BASIC CONSIDERATIONS
PNEUMONIA vs. PNEUMONITIS
DIFFERENTIATION from INJURIES, OBSTRUCTIVE DISEASES, RESTRICTIVE DISEASES, VASCULAR DISEASES
DIFFERENTIATION FROM NEOPLASMS
CLASSICAL STAGES of INFLAMMATION
LOBAR- vs. BRONCHO-
INTERSTITIAL vs. ALVEOLAR
COMMUNITY vs. NOSOCOMIAL
ETIOLOGIC AGENTS vs. HOST IMMUNITY
2 PRESENTING SYMPTOMS
2 DIAGNOSTIC METHODS
ANY ORGANISM CAN CAUSE PNEUMONIA!!!

PREDISPOSING FACTORS
LOSS OF COUGH REFLEX
DIMINISHED MUCIN or CILIA FUNCTION
ALVEOLAR MACROPHAGE INTERFERENCE
VASCULAR FLOW IMPAIRMENTS
BRONCHIAL FLOW IMPAIRMENTS

Although pneumonia is one of the most common causes of death, it usually does NOT occur in healthy people spontaneously

Classifications of PNEUMONIAS
COMMUNITY ACQUIRED
COMMUNITY ACQUIRED, ATYPICAL
NOSOCOMIAL
ASPIRATION
CHRONIC
NECROTIZING/ABSCESS FORMATION
PNEUMONIAS in IMMUNOCOMPROMISED HOSTS

COMMUNITY ACQUIRED
STREPTOCOCCUS PNEUMONIAE (i.e., “diplococcus”)
HAEMOPHILUS INFLUENZAE (“H-Flu”)
MORAXELLA
STAPHYLOCOCCUS (STAPH)
KLEBSIELLA PNEUMONIAE
PSEUDOMONAS AERUGINOSA
LEGIONELLA PNEUMOPHILIA

STREPTOCOCCUS
The classic LOBAR pneumonia
Normal flora in 20% of adults
Only 20% of victims have + blood cultures
“Penicillins” are often 100% curative
Vaccines are often 100% preventive

MORPHOLOGY
ACUTE
ORGANIZING
CHRONIC
FIBROSIS vs. FULL RESOLUTION
“HEPATIZATION”, RED vs. GREY
CONSOLIDATION
“INFILTRATE”, XRAY vs. HISTOPATH
Loss of “CREPITANCE”

VIRAL PNEUMONIAS
Frequently “interstitial”, NOT alveolar

ASPIRATION PNEUMONIAS
UNCONSCIOUS PATIENTS
PATIENTS IN PROLONGED BEDREST
LACK OF ABILITY TO SWALLOW OR GAG
USUALLY CAUSED BY ASPIRATION OF GASTRIC CONTENTS
POSTERIOR LOBES (gravity dependent) MOST COMMONLY INVOLVED, ESPECIALLY THE SUPERIOR SEGMENTS of the LOWER LOBES
Often lead to ABSCESSES

LUNG ABSCESSES
ASPIRATION
SEPTIC EMBOLIZATION
NEOPLASIA
From NEIGHBORING structures:
ESOPHAGUS
SPINE
PLEURA
DIAPHRAGM
ANY pneumonia which is severe and destructive, and UN-treated enough

Lung abscess
Localized suppurative necrosis
Organisms commonly cultured:
Staphylococci
Streptococci
Gram-negative
Anaerobes
Frequent mixed infections
Pathogenesis:
Aspiration
Pneumonia
Septic emboli
Tumors
Direct infection

An abscess can be thought of as a pneumonia in which all of the normal lung outline can no longer be seen, and there is 100% pus.

CHRONIC Pneumonias
USUALLY NOT persistences of the community or nosocomial bacterial infections, but CAN BE, at least histologically
Often SYNONYMOUS with the 4 classic fungal or granulomatous pulmonary infections infections, i.e., TB, Histo-, Blasto-, Coccidio-
If you see pulmonary granulomas, think of a CHRONIC process, often years

CHRONIC Pneumonias
TB
HISTO-PLASMOSIS
BLASTO-MYCOSIS
COCCIDIO-MYCOSIS

GRANULOMA

LUNG TUMORS
Benign, malignant, epithelial, mesenchymal, but 90% are CARCINOMAS
BIGGEST USA killer. Why? Ans: Prevalence not as high as prostate or breast but mortality higher. Only 15% 5 year survival.
TOBACCO has polycyclic aromatic hydrocarbons, such as benzopyrene, anthracenes, radioactive isotopes
Radiation, asbestos, radon
C-MYC, K-RAS, EGFR, HER-2/neu

PATHOGENESIS
NORMAL BRONCHIAL MUCOSA
METAPLASTIC/DYSPLASTIC MUCOSA
CARCINOMA-IN-SITU (squamous, adeno)
INFILTRATING (i.e., “INVASIVE”) cancer

TWO TYPES
NON-SMALL CELL
SQUAMOUS CELL CARCINOMA
ADENOCARCINOMA
LARGE CELL CARCINOMA
SMALL CELL CARCINOMA

The BIG list
Squamous cell carcinoma
Small cell carcinoma
Combined small cell carcinoma
Adenocarcinoma: Acinar, papillary, bronchioloalveolar, solid, mixed subtypes
Large cell carcinoma
Large cell neuroendocrine carcinoma
Adenosquamous carcinoma
Carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements
Carcinoid tumor: Typical, atypical
Carcinomas of salivary gland type
Unclassified carcinoma

The classical squamous cell carcinoma starting in a large bronchus centrally, with bronchial obstruction.
Adenocarcinomas tend to be more peripheral. Note the features of malignant cells on sputum cytology.

Name the four most common histologic patterns of lung carcinoma and explain why!
Squamous, adeno, large, small.

LOCAL effects of LUNG CANCER

METASTATIC TUMORS
LUNG is the MOST COMMON site for all metastatic tumors, regardless of site of origin
It is the site of FIRST CHOICE for metastatic sarcomas for purely anatomic reasons!

PLEURA
PLEURITIS
PNEUMOTHORAX
EFFUSIONS
HYDROTHORAX
HEMOTHORAX
CHYLOTHORAX
MESOTHELIOMAS

PLEURITIS
Usual bacteria, viruses, etc.
Infarcts
Lung abscesses, empyema
TB
“Collagen” diseases, e.g., RA, SLE
Uremia
Metastatic

PNEUMOTHORAX
SPONTANEOUS, TRAUMATIC, THERAPEUTIC
OPEN or CLOSED
“TENSION” pneumothorax, “valvular” effect
“Bleb” rupture
Perforating injuries
Post needle biopsy

EFFUSIONS
TRANSUDATE (HYDROTHORAX)
EXUDATE (HYDROTHORAX)
BLOOD (HEMOTHORAX)
LYMPH (CHYLOTHORAX)

MESOTHELIOMAS
“Benign” vs. “Malignant” differentiation does not matter, but a self limited localized nodule can be regarded as benign, and a spreading tumor can be regarded as malignant
Visceral or parietal pleura, pericardium, or peritoneum
Most are regarded as asbestos caused or asbestos “related”

Typical growth appearance of a malignant mesothelioma, it compresses the lung from the OUTSIDE.