Trans Pulmopatho Colored

OS 213

Dr. Nelia Tan-Liu Exam 1

Pulmonary Pathology Lab Module 1

Lecture Outline: I. Bacterial Pneumonia II. Viral Pneumonia III. Fungal Pneumonia IV. Tuberculosis V. Bronchiectasis VI. Chronic Bronchitis VII. Adult Respiratory Distress Syndrome

Bacterial Pneumonia Case Discussion: A case of a 32 year old male who presented with productive cough, fever and malaise for 8 days. Patient began to experience dyspnea 1 day prior to consult. Chest x-ray showed a diffuse infiltrate between the right middle and right lower lobes.

Common Bacterial Agents in Pnuemonia • Strep pneumoniae • Hemo influenzae • Staph aureus • Klebs pneumoniae • Escherichia coli • Pseudomonas spp. 4 Stages of Inflammation in Bacterial Pneumonia 1. CONGESTION • lung is heavy, boggy, and red • It is characterized by vascular engorgement, intra-alveolar fluid with few neutrophils, and often the presence of numerous bacteria 2. STAGE OF RED HEPATIZATION • characterized by massive confluent exudation with red cells (congestion) and neutrophils and fibrin filling the alveolar spaces • On gross examination, the lobe now appears distinctly red, firm, and airless with a liver-like consistency, hence the term hepatization.

Questions:  Differentiate lobar pneumonia from bronchopneumonia based on the gross features.  Enumerate common bacterial agents isolated in pneumonia.  Enumerate the Stages of Inflammation in Bacterial Pneumonia  Enumerate four possible complications of pneumonia.  Differentiate transudate from exudate  Name other etiologic agents that can give rise to pulmonary abscesses Lobar Pneumonia vs Bronchopneumonia • Lobar pneumonia o A widespread fibrinosuppurative consolidation of large areas and even whole lobes of the lung. Figure 1. Gross picture of lung showing consolidation of a large portion of a lobe or an entire lobe

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Figure 3. Photomicrograph showing intra-alveolar infiltration by acute inflammatory cells (neutrophils) .

3. STAGE OF GREY HEPATIZATION • Progressive disintegration of red cells and the persistence of fibrinosuppurative exudate giving the gross appearance of a grayish brown, dry surface

Bronchopneumonia o Consolidated areas of acute suppurative inflammation. o Consolidation may be patchy through one lobe but is more often multilobar and frequently bilateral and basal because of the tendency of secretions Figure 2. Gross picture of lung showing patchy consolidation of the lung

Figure 4. Slide showing grey hepatization

4. STAGE OF RESOLUTION • Final stage • The consolidated exudate within the alveolar spaces undergoes January 22, 2009 | Thursday

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OS 213

Dr. Nelia Tan-Liu Exam 1

Pulmonary Pathology Lab Module 1

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progressive enzymatic digestion to produce granular, semifluid debris that is resorbed, ingested by macrophages, or coughed up. Pleural fibrinous reaction to the underlying inflammation often present in the early stages if the consolidation extends to the surface (pleuritis), may similarly resolve. More often, it undergoes organization, leaving fibrous thickening or permanent adhesions.

implies significant alteration in the normal permeability of small blood vessels in the area of injury Etiologic Agents Causing Pulmonary Abscesses • Staph aureus • Gram negative organisms • Anaerobic organisms: o Bacteroides o Fusobacterium o Peptococcus o

Viral Pneumonia

Figure 5. Slide showing fibrotic areas with chronic inflammation

Four Possible Complications of Pneumonia • Microabscesses/ abscess • Empyema • Pleural effusion • Bacteremia/ Sepsis

Questions:  Name the common viral agents causing interstitial pneumonia.  Differentiate viral from bacterial pneumonia based on predominant histologic pattern.  Describe cytopathic effects in pneumonia caused by: o Respiratory Syncytial Virus o Cytomegalovirus o Measles  Enumerate three bacterial agents that can present as interstitial pneumonia. Common Viral Agents Causing Interstitial Pneumonia: • Resiratory Syncytial virus • Adenovirus • Rhinovirus • Rubeola • Varicella Viral vs Bacterial Pneumonia (Histology) • The predominant histological pattern in viral pneumonia is the interstitial nature of the inflammatory reaction– inflammation is virtually localized within the walls of the alveoli.

Figure 6. Gross and microscopic pictures of abscess formation (1st two pictures), and empyema

Transudate vs Exudate • Transudate o fluid with low protein count; sp gr of < 1.012 o an ultrafiltrate of blood plasma that results from osmotic or hydrostatic imbalance across the vessel wall without an increase in vascular permeability • Exudate o inflammatory extravascular fluid that has a high protein concentration, cellular debris, and an sp gr of > 1.020

January 22, 2009 | Thursday

Figure 7. Interstitial Pneumonitis

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OS 213

Dr. Nelia Tan-Liu Exam 1

Pulmonary Pathology Lab Module 1 •

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The alveolar septa are widened and edematous and usually have a mononuclear inflammatory infiltrate of lymphocytes, histiocytes, and occasionally plasma cells. In acute cases, neutrophils may also be present. The alveoli may be free from exudate, but in many patients there are intra-alveolar proteinaceous material, a cellular exudate, and characteristically pink hyaline membranes lining the alveolar walls, similar to those seen in hyaline membrane disease of infants.

Book Notes: (Robbins Patho) VIRAL AND MYCOPLASMAL PNEUMONIA (PRIMARY ATYPICAL PNEUMONIA): • The term primary atypical pneumonia was initially applied to an acute febrile respiratory disease characterized by patchy inflammatory changes in the lungs, largely confined to the alveolar septa and pulmonary interstitium. • The term atypical denotes the lack of alveolar exudate, but a much more accurate designation is interstitial pneumonitis. • The pneumonitis is caused by a variety of organisms, the most common being Mycoplasma pneumoniae. Other etiologic agents are viruses, including influenza virus types A and B, the respiratory syncytial viruses, adenovirus, rhinoviruses, rubeola, and varicella viruses; Chlamydia (psittacosis); and Coxiella burnetti (Q fever). [33] In some cases, the cause cannot be determined. • Any one of these agents may cause merely an upper respiratory tract infection, recognized as the common cold, or a more severe lower respiratory tract infection. • The circumstances that favor such extension of the infection are often mysterious but include malnutrition, alcoholism, and underlying debilitating illnesses.

In Fungal Pneumonia, pulmonary damage results from:  vascular occlusion by the fungus, resulting in ischemic necrosis, or  direct invasion by and host reaction to the organism

Figure 8. A lung showing diffuse consolidation and vascular thrombosis with infarction

Figure 9. Close-up view, post-fixation

Cytopathic Effects in Pneumonia • RSV: formation of syncytial cells • CMV: abnormal inclusions or structural changes • Measles: multinucleate giant cells with eosinophilic nuclear and cytoplasmic inclusion bodies (Warthin-Finkeldey cells) • NB: All of these produce essentially similar morphologic patterns (interstitial inflammatory reaction) Bacterial Agents That Can Present as Interstitial Pneumonia • Mycoplasma pneumoniae • Chlamydia trachomatis • Coxiella burnetti

Fungal Pneumonia

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Figure 10. Fungal elements occluding a large pulmonary vessel

Note: January 22, 2009 | Thursday

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OS 213

Dr. Nelia Tan-Liu Exam 1

Pulmonary Pathology Lab Module 1

 Differentiate Langhans’ type from other types of giant cells. Definitive Diagnostic Modality for TB  Culture and isolation  Recent diagnostics involve PCR for mycobacterial nucleic acids in sputum and gastric lavages Gross Facets of TB  Cavitations with casseous material  Fibrosis/Fibrocalcific scars  Hilar lymphadenopathies  Hemorrhage  Consolidation  Bronchial erosions  Pleural effusion  Fibrous pleuritis

Figure 11. Section taken from an invasive pulmonary aspergillosis. (methenamine silver stain)

Questions:  Enumerate 3 conditions leading to an immunocompromised state.  Enumerate other fungal agents that may cause pneumonia. Conditions Leading to an Immunocompromised State: • HIV-AIDS • Chronic steroid use • Malignancies

Figure 12. Pulmonary TB (Ghon complex)

Fungal Agents that may Cause Pneumonia • Histoplasma capsulatum • Blastomyces dermatidis • Coccidioides immitis

Huge tuberculous cavity

Tuberculosis Case Discussion: This is the case of a 56 year old Filipino male who had 2 months history of recurrent febrile episodes in the afternoon, productive cough and weight loss. One week prior to consult, patient began to have blood-tinged sputum and dyspneic episodes. Initial chest x-ray showed hilar lymphadenopathies, bilateral apical cavitations, and minimal pleural effusion on the right. Questions:  Give the definitive diagnostic modality for tuberculosis.  Discuss the different gross facets of tuberculosis.  Enumerate the important histologic features of a TB granuloma January 22, 2009 | Thursday

Early tuberculous cavity formed by caseous (cheese-like) necrosis

Figure 13. Pulmonary TB with Cavitations

Important Histologic Feature of TB Granuloma • A focus of chronic inflammation consisting of microscopic aggregate of macrophages that are transformed into epithelium-like cells surrounded by a collar of mononuclear WBCs Figure 14. TB Granuloma

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OS 213

Dr. Nelia Tan-Liu Exam 1

Pulmonary Pathology Lab Module 1

The right portion of this bronchiole shows epithelial erosion. There is exudate in the lumen. Acute inflammatory cells, especially PMNs, are present, although evidence of chronic inflammation is also likely to be present.

Langhans’ Type vs Other Types of Giant Cells • Langhans: nuclei are arranged in U-shaped pattern • Other giant cells: irregular distribution of nuclei Figure 15. Langhans’ Giant Cells

Bronchiectasis Case Discussion: A case of a 20 year old patient who presented with recurrent fever and productive cough. Sputum gradually became copious, foul and purulent. Initial PE includes bronchial breath sounds on the peripheral lung fields; and bibasal crackles. Definition • Bronchiectasis is the permanent dilation of bronchi and bronchioles and is secondary to cycles of obstruction and infection.

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Figure 16. Cut section of the left lung. Note the inflamed left main stem bronchus. It gives rise to branches in the left lower lobe that have been opened to demonstrate that they extend nearly to the pleural surface in this specimen. The diameters of the two opened bronchial branches in the lower lobe are each greater than the diameter of the bronchus from which they originate, indicating the severity of bronchial dilation.

Figure 17. Section from a bronchiole. There is marked inflammation of the bronchi and bronchiolar walls. The inflammatory cells are seen as dark blue nuclei under the mucosal lining.

January 22, 2009 | Thursday

Questions:  What is your diagnosis?  What are the underlying conditions associated with this condition? What processes are necessary for its development?  What type of inflammatory cells is present? Compare with asthma. Diagnosis: Bronchiectasis Underlying Conditions Associated with Bronchiectasis: • Bronchiectasis is caused by conditions that predispose to chronic necrotizing infections and consequent destruction of muscle and elastic support tissue of bronchi and bronchioles. • The most common conditions are: a. Bronchial obstruction (tumors; foreign bodies), diffuse obstructive airway diseases (atopic asthma; chronic bronchitis) b. Congenital or hereditary conditions (congenital bronchiectasis; cystic fibrosis) c. Necrotizing or suppurative pneumonias Processes Necessary for the Development of Bronchiectasis: • Persistent obstruction • Superimposed infection Type of Inflammatory Cells Present • Acute inflammatory cells, especially PMNs, are present, although evidence of chronic inflammation is also likely to be present. Compare with Asthma • By comparison, in asthma, the inflammatory cells are composed of CD4+ lymphocytes, eosinophils, mast cells, and a few neutrophils.

Chronic Bronchitis Case Discussion: A case of a 62 year old chain-smoker who presented with persistent cough with daily sputum production for almost 10 months each year since 1999. Occasionally, patient spat blood-tinged sputum, but no consult was done until patient had dyspnea, fever, and palpitations. Initial PE revealed cyanosis, dynamic precordium and diffuse crackles on both lungs. Definition Page 5 of 8 Cielo & Co

OS 213

Dr. Nelia Tan-Liu

Pulmonary Pathology Lab Module 1 •

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Chronic bronchitis, per se is defined clinically. It is present in any patient who has persistent cough with sputum production for at least 3 months in at least 2 consecutive years. In simple chronic bronchitis, patients have a productive cough but no physiologic evidence of airflow obstruction. Some individuals may demonstrate hyperreactive airways with intermittent bronchospasm and wheezing. This condition is called chronic asthmatic bronchitis. Finally, some patients, especially heavy smokers, develop chronic airflow obstruction, usually with evidence of associated emphysema, and are classified as showing obstructive chronic bronchitis.

Exam 1

Questions: • What is your diagnosis? Bases? • How does the mucous gland hyperplasia in this case differ from that in a typical case of asthma? • What is the Reid Index? Diagnosis and Basis for It • Chronic bronchitis is a clinical definition: a persistent cough with sputum production for at least three months in two consecutive years. • Characteristic features supporting this diagnosis are hypersecretion of mucous in the large airways, chronic inflammation of the airways (predominantly lymphocytes) and hypertrophy of the submucosal glands in the trachea and bronchi. Mucous Gland Hyperplasia in Chronic Bronchitis (as compared to that in Asthma) • In typical allergic asthma, which also has mucous gland hyperplasia, the bronchial wall has an inflammatory infiltrate in which eosinophils are prominent. • There is also hypertrophy and hyperplasia of smooth muscle cells in asthma.

Figure 18. Trachea and Main Bronchi. The trachea in the mid-upper field is hyperemic, and the bifurcation and main stem bronchi contain mucopurulent exudate. The underlying epithelium is also inflamed. This picture may occur in chronic bronchitis and a superimposed infection. However, one may also see this picture as part of an acute inflammatory process in a patient dying of acute pneumonia. Remember that chronic bronchitis is a clinical term.

Reid Index • The ratio of the thickness of the mucous gland layer to the thickness of the wall between the epithelium and the cartilage. • The normal ratio is 0.4. • It is increased in chronic bronchitis.

Adult Respiratory Distress Syndrome Case Discussion: A case of a 52 year old diabetic, with a history of cerebral infarct and with left-sided residuals, who was diagnosed to have community acquired pneumonia on admission. Patient was admitted for 6 days and was apparently improved on discharge. At home, patient developed high grade fever, body malaise and recurrence of productive cough.

Figure 19. Bronchial Wall. These are changes typical of chronic bronchitis. The bronchial epithelium is partially denuded in some regions but squamous metaplasia is present in others. The basement membrane is thickened (white arrow) and the mucosal vessels are engorged and dilated (thin black arrows). A moderate number of plasmacytes and lymphocytes (thick black arrow) are present in the submucosa and the gland layer which is markedly enlarged and composes almost half of the wall thickness of the bronchus. Majority of 2009 | The Thursday the galnds January are mucous 22, in character. glands and ducts are dilated and filled with mucinous secretion containing desquamated cells and inflammatory cells.

Home medications were continued and consult was done only 5 days later. Patient already presented with difficulty of breathing and was subsequently readmitted. At the wards, patient was hypotensive, tachypneic and febrile. Intubation was done due to sudden respiratory distress and cyanosis. Chest xray showed diffuse bilateral alveolar infiltration. Despite resuscitative efforts, patient demised on the 2nd hospital day. Page 6 of 8 Cielo & Co

OS 213

Dr. Nelia Tan-Liu

Pulmonary Pathology Lab Module 1 Book Notes: (Robbins Patho) ADULT RESPIRATORY DISTRESS SYNDROME (DIFFUSE ALVEOLAR DAMAGE) • ARDS and its many synonyms ( including adult respiratory failure, shock lung, diffuse alveolar damage, acute alveolar injury, and traumatic wet lungs) are descriptive terms for a syndrome caused by diffuse alveolar capillary damage. • It is characterized clinically by the rapid onset of severe life-threatening respiratory insufficiency, cyanosis, and severe arterial hypoxemia that is refractory to oxygen therapy and that may progress to extrapulmonary multisystem organ failure. • ARDS is a well-recognized complication of numerous and diverse conditions, including both direct injuries to the lungs and systemic disorders. Direct lung injuries causing ARDS include diffuse pulmonary and other viral infections, oxygen toxicity, inhalation of toxins and other irritants, and aspiration of gastric contents. Systemic conditions causing ARDS include septic shock, shock associated with trauma, hemorrhagic pancreatitis, burns, complicated abdominal surgery, narcotic overdose and other drug reactions, hypersensitivity reactions to organic solvents, hemodialysis, and cardiac surgery involving extracorporeal pumps. In many cases, a combination of the foregoing conditions is present (e.g., shock, oxygen therapy, and sepsis).

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Figure 20. Lung Section, scanning view. Sections of the lungs show diffused infiltration by inflammatory cells with loss of alveolar architecture. There are areas revealing collection of pink amorphous material and hyalinized deposits. Most areas have necrotic debris with admixed neutrophils.

Figure 21. Lung Section, HPO

January 22, 2009 | Thursday

Exam 1

Questions  What is your histologic diagnosis?  Can the exact etiology be determined by the microscopic findings alone?  What is/are the likely cause(s) in this case? What other conditions can cause these findings?  Enumerate the composition of the hyaline membrane seen in the histologic sections.  What pathologic finding is central to the development of ARDS? Histologic Diagnosis • Diffuse alveolar damage, representing the usual underlying pathologic change of the clinically defined Adult Respiratory Distress Syndrome. Can the exact etiology be determined by the microscopic findings alone? • No. The morphologic changes are nonspecific. • Diffuse Alveolar Damage is best viewed as the pathologic end-result of acute alveolar injury caused by a variety of insults and initiated by different mechanisms. Likely cause in this case • Sepsis, diffuse pulmonary infections, gastric aspiration, and mechanical trauma are responsible for more than 50% of cases of ARDS. Other Conditions that can Cause These Findings • Injuries: o pulmonary contusion o near drowning o fat embolism o burns o ionizing radiation • Inhaled irritants o oxygen toxicity o smoke o irritant gasses and chemicals • Chemical injury o heroin or methadone overdose o aspirin o barbiturate overdose o paraquat • Hematologic conditions o multiple transfusions o DIC • Pancreatitis • Uremia • Cardiopulmonary bypass • Hypersensitivity reactions o organic solvents o drugs Composition of the Hyaline Membrane • The waxy hyaline membranes lining the alveolar walls consist of fibrin-rich edema fluid mixed with the cytoplasmic and lipid remnants of necrotic epithelial cells. Page 7 of 8 Cielo & Co

OS 213 Pulmonary Pathology Lab Module 1

Dr. Nelia Tan-Liu Exam 1

Pathologic Finding Central to Development of ARDS • Diffuse damage to the alveolar capillary walls. Neutrophils are thought to play an important role in the pathogenesis of acute lung injury and ARDS. In contrast, the respiratory distress in newborns is initiated by deficiency in pulmonary surfactant.

January 22, 2009 | Thursday

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