Diseases of the Lung and Respiratory Tract Part
Diseases of the Lung and Respiratory Tract Part
Diseases of the Lung and Respiratory Tract Part
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Pulmonary Pathology II<br />
William Bligh-Glover M.D.<br />
Department <strong>of</strong> Anatomy, CWRU
Goals <strong>and</strong> Objectives<br />
• Comprehend <strong>the</strong> etiology,<br />
pathogenesis/pathopysiology <strong>and</strong><br />
consequences <strong>of</strong> pulmonary hypertension<br />
• Distinguish <strong>the</strong> types <strong>of</strong> lung infection, <strong>and</strong><br />
comprehend <strong>the</strong>ir etiologies,<br />
epidemiology, pathogenesis <strong>and</strong> prognosis<br />
• Comprehend <strong>the</strong> etiology,<br />
pathogenesis/pathophysiology <strong>and</strong><br />
consequences <strong>of</strong> lung abscess
Pulmonary Hypertension<br />
• Defined as at least 25% <strong>of</strong> systemic pressure;<br />
normal is 10% <strong>of</strong> systemic, due to low resistance<br />
<strong>of</strong> pulmonary vasculature<br />
• Hypertension usually due to structural diseases<br />
causing increased pulmonary blood flow or<br />
pressure, increased pulmonary vascular<br />
resistance or left heart resistance<br />
• Note: pulmonary a<strong>the</strong>rosclerosis implies <strong>the</strong>re is<br />
pulmonary hypertension
Pulmonary Hypertension<br />
• Emphysema<br />
– Hypoxia <strong>and</strong> alveolar destruction reduce <strong>the</strong> number <strong>of</strong><br />
capillaries, causing increased arterial resistance,<br />
• Congenital heart disease<br />
– Elevated pressures due to valvular disease<br />
• Recurrent PE<br />
– Reduced area <strong>of</strong> vascular bed with consistent pressures<br />
• VOD<br />
• Fenfluramine/phenterimine<br />
• Idiopathic<br />
– Decreased production <strong>of</strong> nitric oxide <strong>and</strong> prostacyclin <strong>and</strong><br />
increased levels <strong>of</strong> endo<strong>the</strong>lin, leading to endo<strong>the</strong>lial cell<br />
activation <strong>and</strong> thrombogenesis<br />
– Women 20-40
Pulmonary Hypertension<br />
• Treatment<br />
– vasodilators, calcium channel blockers, nitric<br />
oxide, anti-thrombotic medications<br />
• Consequences<br />
– Right heart hypertrophy (Cor pulmonale)<br />
– Dyspnea<br />
– Pneumonia
Recurrent PE
Plexiform Lesions
Cor Pulmonale Cartoon
Cor Pulmonale Gross
Pulmonary Hypertension<br />
• Consequences <strong>of</strong> pulmonary hypertension<br />
– Pulmonary a<strong>the</strong>rosclerosis<br />
– Recurrent thromboemboli<br />
– Intimal thickening<br />
– Plexiform lesions<br />
• Reversible/Irreversible<br />
– Reversible if arterial lesions restricted to medial<br />
hypertrophy, intimal thickening <strong>of</strong> longitudinal smooth<br />
muscle or cellular intimal proliferation<br />
– Irreversible if moderate/severe concentric laminar<br />
intimal fibrosis, fibrinoid necrosis, plexiform lesions
Non-Infectious <strong>Diseases</strong> Leading to<br />
Pulmonary Hypertension<br />
• Acute Interstitial Pneumonia (AIP)<br />
• Bronchiolitis Obliterans Organizing<br />
Pneumonia (BOOP)<br />
• Desquamative Interstitial Pneumonia (DIP)<br />
• Usual Interstitial Pneumonia (UIP)
Acute Interstitial Pneumonia<br />
• Also called Hamman-Rich syndrome<br />
• Rapidly progressive disease with no<br />
identifiable cause; death usually within 2<br />
months<br />
• Young adults with influenza-like illness<br />
followed by shortness <strong>of</strong> breath<br />
• Micro: resembles diffuse alveolar damage<br />
with brisk interstitial fibroblastic<br />
proliferation
Bronchiolitis Obliterans-Organizing<br />
Pneumonia<br />
• Common response to infectious or inflammatory<br />
injury to lungs<br />
• Also associated with drugs, collagen vascular<br />
disease, graft versus host disease in bone<br />
marrow transplant patients<br />
• Cause cannot be determined from biopsy -<br />
requires clinical history<br />
• Acute onset with cough, shortness <strong>of</strong> breath,<br />
fever <strong>and</strong> malaise<br />
• Excellent prognosis; steroid resistance may lead<br />
to death
Desquamative Interstitial<br />
Pneumonitis<br />
• Usually adults with insidious onset <strong>of</strong> shortness<br />
<strong>of</strong> breath, progressing to respiratory<br />
insufficiency; also cough, cyanosis, clubbing<br />
• Cause unknown<br />
• Mean survival 12 years, mortality 28%<br />
• 90% are current or past cigarette smokers<br />
• Associated with collagen vascular disease,<br />
positive ANA (similar to UIP)<br />
• Treatment: steroids (respond better than UIP)
Usual Interstitial Pneumonitis<br />
• Most common pattern <strong>of</strong> idiopathic pulmonary fibrosis<br />
• Usually ages 50+<br />
• 50% have unknown cause with insidious onset<br />
(exertional dyspnea) <strong>and</strong> chronic evolution;<br />
complications include secondary pulmonary<br />
hypertension, cor pulmonale, cardiac failure<br />
• Reduced diffusing capacity is mainly due to ventilationperfusion<br />
mismatch from ventilation <strong>of</strong> lung tissue with<br />
capillary destruction <strong>and</strong> perfusion <strong>of</strong> under ventilated<br />
alveoli<br />
• Treatment: steroids (20% improve)<br />
• Mean survival 6 years, mortality 66%
• Bacterial<br />
Pulmonary Infections<br />
– Pneumococcus<br />
– Mycobacterial<br />
–CF<br />
– Aspiration<br />
•Viral<br />
• Mycoplasma<br />
• Fungal
Pneumonia<br />
• “Old Man’s Friend”—Final common pathway<br />
• <strong>Lung</strong> is #1 site for infections that cause lost workdays<br />
• Impairment <strong>of</strong> defense mechanisms or host resistance<br />
– Normal defense mechanisms:<br />
• Nasal clearance (sneezing, blowing, swallowing)<br />
• Mucociliary elevator (smoking)<br />
• Alveolar clearance (alveolar macrophages)<br />
– Host resistance<br />
• Age<br />
• Intoxication<br />
• O<strong>the</strong>r diseases<br />
• Bronchopneumonia vs. Lobar pneumonia<br />
– Bronchopneumonia<br />
• Patchy consolidation <strong>of</strong> <strong>the</strong> lung centered on bronchi<br />
• Neutrophils in bronchi, bronchioles <strong>and</strong> adjacent alveolar spaces<br />
– Lobar pneumonia<br />
• Consolidation <strong>of</strong> entire lung<br />
• Rare because <strong>of</strong> antibiotics<br />
• Vulnerable patients<br />
– Old<br />
– Young<br />
– Drunks<br />
• Congestion, red hepatization, grey hepatization, resolution
Pneumococcus<br />
(Streptococcus pneumoniae)<br />
– Gram positive, capsulated, lancet-shaped<br />
diplococcus<br />
– <strong>Respiratory</strong> flora<br />
– Pneumonia, Otitis media, Meningitis
Bronchopneumonia Gross
Bronchopneumonia Low Micro
Bronchopneumonia High Micro
Lobar Pneumonia
Pneumococcus
Final Common Pathway<br />
• “Old Man’s Friend”<br />
• Impairment<br />
– Viral pneumonia<br />
– Breaking hip
Tuberculosis<br />
• A.K.A. Consumption, commonest infectious COD in Operas<br />
– Mycobacteria tuberculosis<br />
– Mycobacteria bovis<br />
• <strong>Lung</strong> involvement is <strong>the</strong> major cause <strong>of</strong> morbidity/mortality<br />
– Rarely involves skin, oropharynx, lymphoid tissue<br />
– Pott’s disease (TB <strong>of</strong> spine)<br />
– Prosector’s wart (TB <strong>of</strong> h<strong>and</strong>)<br />
• Suppressed by cell mediated immunity, <strong>the</strong>refore<br />
– Cases increasing due to AIDS<br />
– There have been emergence <strong>of</strong> multiple-drug resistant strains<br />
– Impaired patients not completing a course <strong>of</strong> antibiotics<br />
• Treated with months <strong>of</strong> antibiotics (INH, Rifampin)<br />
• Streptomycin in <strong>the</strong> early days
Mycobacterium tuberculosis<br />
• Acid-fast, slow growing bacillus<br />
• Aerobe<br />
• Two organisms<br />
– M. tuberculosis<br />
– M. bovis
Mycobacterium tuberculosis
Gohn Complex<br />
• Gohn complex<br />
– Parenchymal coin lesion<br />
• Subpleural<br />
• Near upper/lower lobe interlobar fissure<br />
• High oxygen tension)<br />
– Caseous lymph nodes<br />
– Resolution<br />
• Fibrosis<br />
• Calcification<br />
• Asymptomatic
Gohn Complex
Reactivation (Secondary) TB<br />
• 5-10% <strong>of</strong> cases <strong>of</strong> primary infection<br />
• Produces more damage than primary TB<br />
• Apical areas <strong>of</strong> consolidation with caseous<br />
necrosis in draining nodes<br />
• Usually get progressive fibrous encapsulation,<br />
which causes focal pleural adhesions, may<br />
contain anthracotic pigment<br />
• Tubercles coalesce over time, creating confluent<br />
area <strong>of</strong> consolidation
TB Granuloma
TB Granuloma High Power
Saranac Lake
La Boheme
•Not Military TB<br />
Miliary TB<br />
• Looks like lung is shot through with millet<br />
seeds<br />
• Progressive spread in compromised<br />
individuals
Miliary TB
• Influenza<br />
• Parainfluenza<br />
• Adenovirus<br />
Viral Pneumonia<br />
• <strong>Respiratory</strong> syncytial virus<br />
– Children<br />
• Cytomegalovirus, Herpes<br />
– Immunocompromised
Viral Pneumonia Micro
RSV Cytopathic Effect
• Atypical pneumonia<br />
– Walking pneumonia<br />
Mycoplasma<br />
• Interstitial pneumonia, bronchopneumonia<br />
• Often asymptomatic<br />
• Cold agglutinins present in 50% <strong>of</strong> cases<br />
– Anti-I<br />
–IgM
Fungal Pneumonia<br />
• Aspergillus niger<br />
• Pneumocystis carinii<br />
• Histoplasma capsulatum
Aspergillus niger<br />
• Colonization <strong>of</strong> abscess cavity<br />
• Colonization <strong>of</strong> tuberculoma<br />
• Invasive aspergillosis<br />
– Immunocompromised<br />
•AIDS<br />
• Transplants<br />
– Associated with renal transplant recipients
Aspergilloma Gross
Aspergillus Fungus Ball
Aspergillus Micro<br />
• Vessel tropic fungus<br />
• “Holy-water sprinkler”
Aspergillus Micro
Pneumocystis carinii<br />
• AIDS defining illness<br />
– Opportunistic fungus<br />
• bronchoalveolar lavage, biopsy<br />
• Most common pneumonia in AIDS<br />
patients,<br />
– CD4 < 200<br />
– protein-calorie malnutrition<br />
• Causes diffuse or patchy pneumonia<br />
• Little fungi on GMS
P. carinii
Pulmonary Abscess<br />
• Causes<br />
– Sino bronchial infections<br />
– Dental sepsis<br />
– Obstruction<br />
– Bronchiectasis<br />
– Aspiration<br />
• Alcoholism<br />
• Coma<br />
• Drugs<br />
• Debilitation<br />
– 10% <strong>of</strong> cases are associated with underlying carcinoma<br />
• Aspiration induced abscesses more common on right side<br />
– Right middle, right lower lobes<br />
– Right sided bronchus straight shot<br />
• Cough, fever, copious foul-smelling sputum, chest pain,
Pulmonary Abscess Gross
Aspiration Pneumonia
Pulmonary Abscess<br />
Necrotizing infection with tissue destruction
Pleuritis
Consequences <strong>of</strong> Abscesses<br />
• Empyema<br />
• Hemothorax<br />
• Sepsis<br />
• Adhesions