Pulmonary Pathology II

William Bligh-Glover M.D.Department of Anatomy, CWRU

Goals and Objectives

• Comprehend the etiology, pathogenesis/pathopysiology and consequences of pulmonary hypertension

• Distinguish the types of lung infection, and comprehend their etiologies, epidemiology, pathogenesis and prognosis

• Comprehend the etiology, pathogenesis/pathophysiology and consequences of lung abscess

Pulmonary Hypertension

• Defined as at least 25% of systemic pressure; normal is 10% of systemic, due to low resistance of pulmonary vasculature

• Hypertension usually due to structural diseases causing increased pulmonary blood flow or pressure, increased pulmonary vascular resistance or left heart resistance

• Note: pulmonary atherosclerosis implies there is pulmonary hypertension

Pulmonary Hypertension• Emphysema

– Hypoxia and alveolar destruction reduce the number of capillaries, causing increased arterial resistance,

• Congenital heart disease– Elevated pressures due to valvular disease

• Recurrent PE– Reduced area of vascular bed with consistent pressures

• VOD• Fenfluramine/phenterimine• Idiopathic

– Decreased production of nitric oxide and prostacyclin and increased levels of endothelin, leading to endothelial cell activation and thrombogenesis

– Women 20-40

Pulmonary Hypertension

• Treatment– vasodilators, calcium channel blockers, nitric

oxide, anti-thrombotic medications• Consequences

– Right heart hypertrophy (Cor pulmonale)– Dyspnea– Pneumonia

Recurrent PE

Plexiform Lesions

Cor Pulmonale Cartoon

Cor Pulmonale Gross

Pulmonary Hypertension• Consequences of pulmonary hypertension

– Pulmonary atherosclerosis– Recurrent thromboemboli– Intimal thickening– Plexiform lesions

• Reversible/Irreversible– Reversible if arterial lesions restricted to medial

hypertrophy, intimal thickening of longitudinal smooth muscle or cellular intimal proliferation

– Irreversible if moderate/severe concentric laminar intimal fibrosis, fibrinoid necrosis, plexiform lesions

Non-Infectious Diseases Leading to Pulmonary Hypertension

• Acute Interstitial Pneumonia (AIP)• Bronchiolitis Obliterans Organizing

Pneumonia (BOOP)• Desquamative Interstitial Pneumonia (DIP)• Usual Interstitial Pneumonia (UIP)

Acute Interstitial Pneumonia

• Also called Hamman-Rich syndrome• Rapidly progressive disease with no

identifiable cause; death usually within 2 months

• Young adults with influenza-like illness followed by shortness of breath

• Micro: resembles diffuse alveolar damage with brisk interstitial fibroblastic proliferation

Bronchiolitis Obliterans-Organizing Pneumonia

• Common response to infectious or inflammatory injury to lungs

• Also associated with drugs, collagen vascular disease, graft versus host disease in bone marrow transplant patients

• Cause cannot be determined from biopsy -requires clinical history

• Acute onset with cough, shortness of breath, fever and malaise

• Excellent prognosis; steroid resistance may lead to death

Desquamative Interstitial Pneumonitis

• Usually adults with insidious onset of shortness of breath, progressing to respiratory insufficiency; also cough, cyanosis, clubbing

• Cause unknown• Mean survival 12 years, mortality 28%• 90% are current or past cigarette smokers• Associated with collagen vascular disease,

positive ANA (similar to UIP)• Treatment: steroids (respond better than UIP)

Usual Interstitial Pneumonitis• Most common pattern of idiopathic pulmonary fibrosis• Usually ages 50+• 50% have unknown cause with insidious onset

(exertional dyspnea) and chronic evolution; complications include secondary pulmonary hypertension, cor pulmonale, cardiac failure

• Reduced diffusing capacity is mainly due to ventilation-perfusion mismatch from ventilation of lung tissue with capillary destruction and perfusion of under ventilated alveoli

• Treatment: steroids (20% improve)• Mean survival 6 years, mortality 66%

Pulmonary Infections

• Bacterial– Pneumococcus– Mycobacterial– CF– Aspiration

• Viral• Mycoplasma• Fungal

Pneumonia• “Old Man’s Friend”—Final common pathway• Lung is #1 site for infections that cause lost workdays• Impairment of defense mechanisms or host resistance

– Normal defense mechanisms: • Nasal clearance (sneezing, blowing, swallowing)• Mucociliary elevator (smoking)• Alveolar clearance (alveolar macrophages)

– Host resistance• Age• Intoxication• Other diseases

• Bronchopneumonia vs. Lobar pneumonia– Bronchopneumonia

• Patchy consolidation of the lung centered on bronchi• Neutrophils in bronchi, bronchioles and adjacent alveolar spaces

– Lobar pneumonia• Consolidation of entire lung• Rare because of antibiotics• Vulnerable patients

– Old– Young– Drunks

• Congestion, red hepatization, grey hepatization, resolution

Pneumococcus

(Streptococcus pneumoniae)– Gram positive, capsulated, lancet-shaped

diplococcus– Respiratory flora– Pneumonia, Otitis media, Meningitis

Bronchopneumonia Gross

Bronchopneumonia Low Micro

Bronchopneumonia High Micro

Lobar Pneumonia

Pneumococcus

Final Common Pathway

• “Old Man’s Friend”• Impairment

– Viral pneumonia– Breaking hip

Tuberculosis• A.K.A. Consumption, commonest infectious COD in Operas

– Mycobacteria tuberculosis– Mycobacteria bovis

• Lung involvement is the major cause of morbidity/mortality– Rarely involves skin, oropharynx, lymphoid tissue– Pott’s disease (TB of spine)– Prosector’s wart (TB of hand)

• Suppressed by cell mediated immunity, therefore– Cases increasing due to AIDS – There have been emergence of multiple-drug resistant strains– Impaired patients not completing a course of antibiotics

• Treated with months of antibiotics (INH, Rifampin)• Streptomycin in the early days

Mycobacterium tuberculosis

• Acid-fast, slow growing bacillus• Aerobe• Two organisms

– M. tuberculosis– M. bovis

Mycobacterium tuberculosis

Gohn Complex

• Gohn complex– Parenchymal coin lesion

• Subpleural• Near upper/lower lobe interlobar fissure • High oxygen tension)

– Caseous lymph nodes– Resolution

• Fibrosis• Calcification • Asymptomatic

Gohn Complex

Reactivation (Secondary) TB

• 5-10% of cases of primary infection• Produces more damage than primary TB• Apical areas of consolidation with caseous

necrosis in draining nodes• Usually get progressive fibrous encapsulation,

which causes focal pleural adhesions, may contain anthracotic pigment

• Tubercles coalesce over time, creating confluent area of consolidation

TB Granuloma

TB Granuloma High Power

Saranac Lake

La Boheme

Miliary TB

• Not Military TB• Looks like lung is shot through with millet

seeds• Progressive spread in compromised

individuals

Miliary TB

Viral Pneumonia

• Influenza• Parainfluenza• Adenovirus• Respiratory syncytial virus

– Children • Cytomegalovirus, Herpes

– Immunocompromised

Viral Pneumonia Micro

RSV Cytopathic Effect

Mycoplasma

• Atypical pneumonia– Walking pneumonia

• Interstitial pneumonia, bronchopneumonia• Often asymptomatic• Cold agglutinins present in 50% of cases

– Anti-I– IgM

Fungal Pneumonia

• Aspergillus niger• Pneumocystis carinii• Histoplasma capsulatum

Aspergillus niger

• Colonization of abscess cavity• Colonization of tuberculoma• Invasive aspergillosis

– Immunocompromised• AIDS• Transplants

– Associated with renal transplant recipients

Aspergilloma Gross

Aspergillus Fungus Ball

Aspergillus Micro

• Vessel tropic fungus• “Holy-water sprinkler”

Aspergillus Micro

Pneumocystis carinii

• AIDS defining illness– Opportunistic fungus

• bronchoalveolar lavage, biopsy

• Most common pneumonia in AIDS patients, – CD4 < 200 – protein-calorie malnutrition

• Causes diffuse or patchy pneumonia• Little fungi on GMS

P. carinii

Pulmonary Abscess• Causes

– Sino bronchial infections– Dental sepsis– Obstruction– Bronchiectasis– Aspiration

• Alcoholism • Coma• Drugs• Debilitation

– 10% of cases are associated with underlying carcinoma • Aspiration induced abscesses more common on right side

– Right middle, right lower lobes– Right sided bronchus straight shot

• Cough, fever, copious foul-smelling sputum, chest pain,

Pulmonary Abscess Gross

Aspiration Pneumonia

Pulmonary AbscessNecrotizing infection with tissue destruction

Pleuritis

Consequences of Abscesses

• Empyema• Hemothorax• Sepsis• Adhesions