Lecture Pathology ppt

Case Study: 13-Month-Old Girl

• Patient: 13-month-old girl
• Symptoms: Altered general status, fever, headache, lethargy, diarrhea
• Initial Diagnosis: Viral enterocolitis (COVID-19 negative)
• Outcome: Sudden death
• Key Developments:
  • No significant improvement after one week of hospitalization.
  • Re-hospitalization for cardiac investigations.
  • Suspicion of congenital cardiac malformation.
  • Suspicion of myocarditis.
• Action Taken: Autopsy required by cardiologist.

Pathology of the Respiratory System - Overview

• Discipline: Pathology of the Respiratory System
• Year of Study: 3rd Year
• Professor: Simona Gurzu, MD, PhD
• Date: April 2025
• Key Areas of Study:
  • Lesions of the upper respiratory tract (pp. 545-547)
  • Pathology of the lung
    • Disorders of the pulmonary air content: Atelectasis and respiratory distress syndrome of the adult and newborn (pp. 495-497, 278-279)
    • Obstructive lung diseases (pp. 498-499, 500-506)
    • Pulmonary infections: Pneumonias (pp. 519-525)
    • Injury by nontherapeutic toxic agents (drug abuse) (pp. 315-317)
    • Chronic interstitial lung diseases and smoking-related interstitial diseases (pp. 506-508; 514-515)
    • Lung tumors (pp. 537-544)
  • Pleural diseases (pp. 544-545)

Respiratory System Terminology

• General Anatomy:
  • Aparat respirator: respiratory system, appareil respiratoire
  • Plămân drept: right lung, poumon droit
  • Plămân stâng: left lung, poumon gauche
• Upper Respiratory Tract:
  • Epiglotă: epiglottis, épiglotte
  • Cavitate nazală: nasal cavity, cavité nasale
  • Faringe: pharynx, pharynx
  • Cavitate bucală: oral cavity, cavité buccale
  • Esofag: oesophagus, desophage
  • Laringe: larynx, larynx
  • Coardă vocală: vocal cord, corde vocale
• Lung Lobes:
  • Lob superior: upper lobe, lobe supérieur
  • Lob median: middle lobe, lobe moyen
  • Lob inferior: lower lobe, lobe inférieur
• Related Structures:
  • Pericard: pericardum, péricarde
  • Inimă: heart, cœur
  • Diafragma: diaphragm, diaphragme
  • Trahee: trachea, trachée
  • Aortă: aorta, aorte
  • Arteră pulmonară: pulmonary artery, artère pulmonaire

Smoking History

• 1 pack a day for 20 years.

Pathology of the Nose, Middle Ear, and Paranasal Sinuses

• Etiology:
  • Common Viruses: Rhinoviruses, Coronavirus, Sincitial Respiratory Virus, Adeno-enteroviruses
  • Less Common: Coxsackievirus A, EBV, Streptococcus β-hemolytic group A
  • Unknown causes account for 40% of cases.
• Rhinitis (Inflammation of the Nasal Mucosa):
  • Acute catarrhal rhinitis (common cold)
  • Acute necrotizing rhinitis
  • Allergic rhinitis: seasonal, perennial
  • Chronic rhinitis: hyperplastic polyp, atrophic rhinitis
• Related Conditions:
  • Rhinopharyngitis, Pharyngotonsillitis (more common in infants)
  • Otitis: acute, chronic (cholesteatoma)
  • Sinusitis: acute, chronic
  • Kartagener syndrome: sinusitis + bronchiectasis + situs inversus (defective ciliary function)
• Specific Inflammations:
  • Tuberculosis
  • Syphilis
  • Rhinoscleroma
  • Fungi (Rhinosporidiosis)
  • Wegener’s granulomatosis

Nasal Polyps

• Hyperplastic polyps are noted.

Anatomy of the Ear

• Outer Ear: Ear canal, Ear drum
• Middle Ear: Malleus, Incus, Stapes
• Inner Ear: Cochlear, Semicircular canals
• Nerves: Facial nerve, Auditory nerve, Vestibular nerve
• Other: Eustachean tube

Sinusitis

• Chronic Sinusitis: Affecting the ethmoid and maxillary sinuses.

Rhinoscleroma

• Etiology: Klebsiella Rhinoscleromatis
• Histopathology: Presence of Russel's bodies and Mikulicz cells.

Wegener's Granulomatosis

• Mentioned as a specific inflammation affecting the nose and paranasal sinuses.

Rhinophyma

• Definition: Hyperplasia of sebaceous glands.
  Note: A reference to a painting depicting an old man with rhinophyma being observed by his grandson is included.

Tumors of the Nose and Paranasal Sinuses

• Benign Tumors:
  • Papilloma
  • Haemangioma
  • Angiofibroma
  • Adenoma
• Malignant Tumors:
  • Nasopharyngeal carcinomas
  • Squamous cell carcinoma
    • HPV-related
    • Undifferentiated (lymphoepithelial) carcinoma, often EBV-associated
  • Adenocarcinoma, adenoid cystic carcinoma
  • Malignant melanoma
  • Lymphomas
    • Burkitt lymphoma (EBV-related)
    • Other non-Hodgkin lymphomas

Inverted Papilloma

• Characterized by inward growth.

Juvenile Angiofibroma

• Mentioned with a visual reference. (ЗІЯТЭМ)

Nasopharyngeal Carcinoma

• Location indicated in axial, sagittal and coronal diagrams relative to the soft and hard palate.

Anatomy of the Larynx

• Key Structures:
  • Epiglottis
  • Ventriculus laryngis
  • Stimmband (vocal cord)
  • Schildknorpel (thyroid cartilage)
  • Luftröhre (trachea)
• Regions:
  • Supraglottischer Raum (supraglottic space)
  • Glottischer Raum (glottic space)
  • Infra-glottischer Raum (infraglottic space)

Diseases of the Larynx

• Laryngeal Edema: Causes include allergies, inflammations, and tumors.
• Laryngeal Stenosis: Caused by obstruction or compression.
• Laryngitis:
  • Acute catarrhal laryngitis: caused by viruses, allergies
  • Acute epiglottitis: caused by Hemophilus influenzae
  • Acute pseudomembranous laryngitis (diphteric croup): caused by Corynebacterium diphtheriae
  • Acute necrotizing laryngitis
  • Chronic laryngitis with leukoplakia
  • Specific inflammations: tuberculosis, syphilis, Wegener’s granulomatosis

Laryngeal Obstruction

• Can be caused by food.

Laryngotracheitis

Croup and Necrotizing Tracheitis

Trachea

• Post-Tracheostomy Changes: Scarring, subglottic tracheostenosis.
• Infectious Tracheitis: Hemorrhagic (Influenza), pseudomembranous-necrotizing.
• Other: Carcinoma.

Hemorrhagic-Fibrinous Laryngo-Tracheitis

Epiglottis Cyst

Tuberculous Laryngitis

• Forms: Pseudopolipous, ulcerative.

Tumors of the Larynx

• Benign Tumors:
  • Papilloma, papillomatosis (HPV 6 and 11)
  • Singer’s node (laryngeal polyp)
• Malignant Tumors:
  • Squamous cell carcinoma:
    • Supraglottic: metastasizes to cervical lymph nodes
    • Glottic: best prognosis
    • Subglottic: rare
  • Complications: asphyxia, necrotic pneumonia, hemorrhages
  • Sarcomas, malignant lymphomas

Pseudotumors and Tumors of the Larynx

• Includes:
  • Singer's node
  • Papilloma
  • Cancer on vocal cord

Papillomatosis

Supraglottic Carcinomas

Glottic Carcinomas

• Ulcerated and papillomatous tumors.

Subglottic Carcinoma

Laryngeal Carcinomas - Advanced Stages

pTNM Staging

Pathology of the Respiratory System - Revisited

• Key Areas of Study:
  • Lesions of the upper respiratory tract (pp. 545-547)
  • Pathology of the lung
    • Disorders of the pulmonary air content: Atelectasis and respiratory distress syndrome of the adult and newborn (pp. 495-497, 278-279)
    • Obstructive lung diseases (pp. 498-499, 500-506)
    • Pulmonary infections: Pneumonias (pp. 519-525)
    • Injury by nontherapeutic toxic agents (drug abuse) (pp. 315-317)
    • Chronic interstitial lung diseases and smoking-related interstitial diseases (pp. 506-508; 514-515)
    • Lung tumors (pp. 537-544)
  • Pleural diseases (pp. 544-545)

Congenital Disorders of the Lung

• Lung hypoplasia
• Polycystic lung
• Kartagener’s syndrome:
  • Situs inversus + bronchiectasis + chronic rhinosinusitis + lack of the frontal sinuses
  • Defective ciliary function
• Cystic fibrosis
• \alpha-1-Antitrypsin deficiency

Congenital Malformations

• Lung hypoplasia, Polycystic lung (cystic dysplasia)

Cystic Fibrosis

Disorders of Lung Circulation

• Lung hyperemia
• Lung congestion
• Embolism, DIC (Disseminated Intravascular Coagulation)
• Lung infarction
• Lung hemorrhages (Goodpasture syndrome)
• Pulmonary hypertension

Acute Pulmonary Edema

Chronic Pulmonary Congestion

• Brown induration of the lung is a characteristic feature.

Thromboembolism

• Pulmonary arteriography is used for diagnosis.
• Deep leg vein thrombosis is a common source.
• Outcomes:
  • Sudden death: Massive coiled embolus in main pulmonary artery
  • Pulmonary infarct: Small embolus lodged in peripheral pulmonary artery
  • Pulmonary hypertension: Multiple repeated small emboli

Thromboembolism and Lung Infarction

Embolism

• Bone marrow embolism
• Bone marrow embolism and DIC

Disseminated Intravascular Coagulation (DIC)

• Characterized by thrombi.

Goodpasture Syndrome

• Lung hemorrhages and hemosiderosis.

Bronchitis, Bronchiolitis

• Acute Bronchitis Types: Catarrhal, muco-purulent diphtheric croup, hemorrhagic, necrotizing, ulcerative
• Evolution and Complications:
  • Healing
  • Chronic bronchitis, bronchopneumonia
  • Obstruction of the small bronchi leading to focal atelectasis
  • Necrotizing bronchitis leading to lung gangrene
  • Diphteric croup leading to asphyxia

Acute Bronchitis Types

• Classified by severity of inflammation and necrosis:
  • Catarrhal (Katarrhalisch-schleimige)
  • Purulent (Eitrige)
  • Fibrinous (Fibrinöse)
  • Necrotizing (Nekrotisierende, Diphtherisch-pseudomembranös)

Mucopurulent Bronchitis

Acute Bronchitis and Bronchiolitis

Bronchiolitis

• Occurs in children and the elderly.
• Types:
  • Purulent bronchiolitis: Can lead to healing, bronchopneumonia, or asphyxia
  • Bronchiolitis obliterans: Associated with viruses, toxins, collagen diseases, lung transplantation; can lead to luminal obstruction, atelectasis, and death

Bronchiolitis Obliterans

Pathology of the Respiratory System - Revisited

• Key Areas of Study:
  • Lesions of the upper respiratory tract (pp. 545-547)
  • Pathology of the lung
    • Disorders of the pulmonary air content: Atelectasis and respiratory distress syndrome of the adult and newborn (pp. 495-497, 278-279)
    • Obstructive lung diseases (pp. 498-499, 500-506)
    • Pulmonary infections: Pneumonias (pp. 519-525)
    • Injury by nontherapeutic toxic agents (drug abuse) (pp. 315-317)
    • Chronic interstitial lung diseases and smoking-related interstitial diseases (pp. 506-508; 514-515)
    • Lung tumors (pp. 537-544)
  • Pleural diseases (pp. 544-545)

Obstructive vs Restrictive Lung Disorders

• Obstructive Lesions:
  • Affect the airways, characterized by improper airflow due to increased pressure (partial or complete obstruction).
  • Examples: COPD (chronic bronchitis, asthma, bronchiectasis, emphysema)
• Restrictive Lesions:
  • Decrease lung parenchyma expansion, reducing total pulmonary capacity.
  • Examples:
    • Pulmonary diseases: ARDS, pneumoconioses, interstitial fibrosis, lesions induced by smoking and drugs, sarcoidosis, TB, etc.
    • Thoracic wall disorders: obesity, pleural disorders
    • Neurological diseases (e.g., Guillain-Barre syndrome)

Chronic Obstructive Pulmonary Diseases (COPD)

• Includes chronic bronchitis, bronchial asthma, bronchiectasis, and chronic emphysema.
• Can lead to chronic cor pulmonale.
• Lung surface area is approximately 80 m\textsuperscript{2}.
• Daily air volume is 15,000-20,000 liters.

Chronic Cor Pulmonale

Chronic Bronchitis

• Clinical Definition: Cough + sputum for 3 months in two consecutive years.
• Etiology: Smoking, air pollution (smog).
• Classification:
  • Simple chronic bronchitis
  • Chronic asthmatic bronchitis (Intrinsic asthma)
• Consequences:
  • Pneumonia, lung emphysema, lung fibrosis, bronchiectasis
  • Chronic cor pulmonale

Chronic Bronchitis (Histological Images)

Chronic Bronchitis - Types

• Types: hypertrophic and atrophic (with squamous metaplasia).

Chronic Obstructive Pulmonary Diseases (COPD) - Revisited

• Includes chronic bronchitis, bronchial asthma, bronchiectasis, and chronic emphysema.
• Can lead to chronic cor pulmonale.
• Lung surface area is approximately 80 m\textsuperscript{2}.
• Daily air volume is 15,000-20,000 liters.

Bronchial Asthma

• Episodic, reversible small airways obstruction.
  • Involves bronchospasm + inflammation + mucus hypersecretion + edema.
• Asthmatic attacks can cause acute emphysema.
• Can progress to status asthmaticus.
• Etiology:
  • Atopic asthma (seasonal, familial, extrinsic)
  • Non-atopic asthma (intrinsic)
  • Drug-related asthma (aspirin)
  • Occupational asthma
  • Allergic bronchopulmonary aspergillosis (mould fungus)
• Consequences:
  • Pneumothorax, bronchiectasis, lung emphysema, chronic cor pulmonale (CCP)
  • Prolonged status asthmaticus can lead to death

Immediate Hypersensitivity (Type I)

• Key components: Antigen, mast cells, IgE receptor, Antigen-specific IgE.
• Mediators released from mast cells:
  • Preformed mediators (Histamine, chemokines, Kallikrein generating factor, Proteases, Peroxidase, Proteoglycans, Inflammatory factors of anaphylaxis)
  • Newly synthesized mediators (Prostaglandins, Leukotrienes)

Bronchial Asthma

Asthma

Characterized by:

• Acute emphysema
• Mucus hypersecretion

Chronic Obstructive Pulmonary Diseases (COPD) - Revisited

• Includes chronic bronchitis, bronchial asthma, bronchiectasis, and chronic emphysema.
• Can lead to chronic cor pulmonale.
• Lung surface area is approximately 80 m\textsuperscript{2}.
• Daily air volume is 15,000-20,000 liters.

Bronchiectasis

• Types:
  • congenital
  • acquired (children / adults)
  • diffuse and localized
• Causes:
  • Weakness of the bronchial wall (chronic bronchitis, cystic fibrosis)
  • Increasing of the bronchial pressure (winds, asthma…)
  • Fibrosis of the lung parenchyma (radiotherapy)
• Morphology:
  • Dilatation of the bronchi, mucus and pus in lumen
  • Inflammatory infiltrate within walls, squamous metaplasia
• Consequences:
  • Pneumonia, lung abscesses, necrotizing bronchitis
  • Lung fibrosis, chronic cor pulmonale
  • Prolonged toxemia → cachexia
  • Systemic metastatic abscesses – especially in brain
  • Systemic amyloidosis

Congenital Bronchiectasis, Polycystic Lung and Mucoviscidosis

Bronchiectasis - Types

• Localized vs. diffuse.

Bronchiectasis

• Bronchiectasis cavernae.

Case Presentation: Chronic Lung Fibrosis and Cor Pulmonale

• 78-year-old man
• Chronic lung fibrosis + cor pulmonale
• Bronchopneumonia+pleuritis → right ventricle failure
• Death

Chronic Obstructive Pulmonary Diseases (COPD) - Revisited

• Includes chronic bronchitis, bronchial asthma, bronchiectasis, and chronic emphysema.
• Can lead to chronic cor pulmonale.
• Lung surface area is approximately 80 m\textsuperscript{2}.
• Daily air volume is 15,000-20,000 liters.

Bob, I've got emphysema.

Emphysema - Key Features

• Stenosis
• Obstruction
• Atelectasis

Normal Lung vs. Emphysema

• Newborn vs adult.

Emphysema

• (emphysaein, gr.= to inflate)
• Types of Emphysema:
  • Emphysema of the air spaces:
    • Acute emphysema
    • Vicariant (compensatory) emphysema
    • Senile emphysema
    • Chronic obstructive emphysema
  • Interstitial Emphysema

Acute Emphysema

• acute and reversible overdistension of the lung, without tissue destruction.
• Causes: disorders of respiration, asphyxia, bronchial asthma.
• Macroscopy: pale and overdistended lungs.
• Microscopy: dilated alveolar spaces.
• Evolution: reversible process.

Acute Emphysema

Vicariant (Compensatory) Emphysema

• Acute or chronic dilated spaces around atelectatic areas.

Senile Emphysema

• Senile lung atrophy.
• Macroscopy: spongy-like small lungs, emphysematous thorax without Chronic Cor Pulmonale!

Chronic Emphysema

• Permanent dilatation of the air spaces, distal to the terminal bronchiole, associated with the destruction of the alveolar walls.
• Pathogenesis:
  • Dilatation of the air spaces
  • Progressive atrophy of the lung parenchyma
  • Atrophy of the vascular network (pulmonary hypertension)
• Macroscopy:
  • Overdistended lungs, spongy-like aspect on section
  • Often associated with chronic bronchitis
• Microscopy:
  • Large alveolar spaces
  • Thin and broken alveolar septa
  • Stretched capillaries

Chronic Emphysema - Diagram

Normal Lung vs. Emphysema - Diagram

Lung Emphysema

Normal Lung and Emphysema

LUNG EMPHYSEMA

Diagnosis of Lung Emphysema

Chronic Emphysema – Etiology and Pathogenesis

• Exogenous Agents:
  • Chronic bronchitis
  • Proteolysis
  • Difficulty in expiration (inflammatory exudate) leads to dilatation of the air spaces, destruction of wall structure, and fusion of the air spaces
• Endogenous Factors:
  • \alpha-1 antitrypsin deficiency (lack of antiproteases)
  • Immune mechanisms

Chronic Emphysema - Pathogenesis

• Tobacco Smoke:
  • Nicotine promotes inflammation via IL-8 release.
  • Reactive oxygen species inactivate antiproteases, leading to "functional" \alpha-1AT deficiency.
  • Neutrophil and macrophage elastases cause tissue damage.
• Congenital α1-AT deficiency also contributes to emphysema.

Chronic Emphysema - Types

• Centriacinar, Panacinar

Bullous Emphysema

Chronic Emphysema - Consequences

• Chronic hypoxia → pulmonary hypertension → chronic cor pulmonale
• Atrophy of the lung parenchyma → respiratory failure
• Rupture of bullae → pneumothorax

Emphysematous Thorax

• Visual features Blebs on pleural surface, small bullae within lung, arteriolar sclerosis, Chronic cor pulmonale.

Interstitial Emphysema

• Penetration of air into the lung interstitium.
• Causes: Cough, trauma, artificial respiration (high pressure).
• Consequences: Mediastinal emphysema, subcutaneous emphysema, pneumothorax.

Interstitial Emphysema - Diagram Subcutaneous Emphysema

Interstitial Emphysema

Pathology of the Respiratory System - Revisited

*Key Areas of Study:
*Lesions of the upper respiratory tract (pp. 545-547)
*Pathology of the lung
*Disorders of the pulmonary air content: Atelectasis and respiratory distress syndrome of the adult and newborn (pp. 495-497, 278-279)
*Obstructive lung diseases (pp. 498-499, 500-506)
*Pulmonary infections: Pneumonias (pp. 519-525)
*Injury by nontherapeutic toxic agents (drug abuse) (pp. 315-317)
*Chronic interstitial lung diseases and smoking-related interstitial diseases (pp. 506-508; 514-515)
*Lung tumors (pp. 537-544)
*Pleural diseases (pp. 544-545)

Bullous Emphysema and Atelectasis

Atelectasis (Collapse)

• Atelectasis
• Dystelectasis
  • Neonatal atelectasis
    • Primary atelectasis = lung anectasis (intrauterine death)
    • Secondary atelectasis = dystelectasis
      • Causes: Lack of surfactant, preterm babies, aspiration of amniotic fluid

Acquired Atelectasis

• Types: resorption, compression, scarring (contraction)
• Consequences:
  • Reversible process
  • Superinfection: pneumonia, purulent inflammation

Atelectasis

Diagram: Normal lung vs. atelectasis

Total and Focal Atelectasis

Dystelectasis

Aspiration of Amniotic Fluid

Respiratory Distress Syndrome

• Acute restrictive lung disease causing progressive respiratory failure.
• Alveoli are lined by hyaline membranes.
• Types:
  • Hyaline membrane disease (Infant Respiratory Distress Syndrome):
    • Preterm babies, Cesarean intervention, mother’s diabetes.
    • Lack of surfactant leads to:
      • Dystelectasia
      • Congestion
      • Plasma exudation
      • Hyaline membranes
    • Treatment: exogenous surfactant; oxygenotherapy (may induce retrolenticular fibroplasia (preterm retinopathy) and bronchopulmonary dysplasia, intraventricular hemorrhage, necrotic enterocolitis, PAC).
  • Adult respiratory distress syndrome (ARDS), shock lung:
    • DIC + destruction of surfactant leads to:
      • Dystelectasis
      • Hemorrhages
      • Hyaline membranes
    • Death rate: 40%

Phases of Respiratory Distress Syndrome

• Exudative phases I, II, III
• Proliferative Phase

Dystelectasis - Shock

ARDS - Hyaline Membranes

Pathology of the Respiratory System - Revisited

• Key Areas of Study:
  • Lesions of the upper respiratory tract (pp. 545-547)
  • Pathology of the lung
    • Disorders of the pulmonary air content: Atelectasis and respiratory distress syndrome of the adult and newborn (pp. 495-497, 278-279)
    • Obstructive lung diseases (pp. 498-499, 500-506)
    • Pulmonary infections: Pneumonias (pp. 519-525)
    • Injury by nontherapeutic toxic agents (drug abuse) (pp. 315-317)
    • Chronic interstitial lung diseases and smoking-related interstitial diseases (pp. 506-508; 514-515)
    • Lung tumors (pp. 537-544)
  • Pleural diseases (pp. 544-545)

Marijuana abuse.

Illicit Drug Use

• Inhaled drugs, water pipe smoking and injected drugs.

Cocaine

• Isolated in 1855 from Erythroxylum coca
• Carl Koller introduced it as a local anesthetic.
• Sigmund Freud initially studied its effects, opposite to morphine.
• 1863 - Angelo Mariani's wine containing 6 mg of cocaine per ounce awarded by pope Leo XIII.

Cocaine History

• Parke-Davis marketed cocaine in various forms, claiming it provided the effects of food, bravery and eloquence.
• John Styth Pemberton created French Wine Cola, later Coca-Cola, with caffeine and cocaine. (Later removed).
• 2006 - UNODC: Approximately 5% of the world population (age 15-64) use illicit drugs annually.

Illicit Drug Use - Consequences

• Immunity, administration route/concentration, associated substances affect outcomes.
• Heroin overdose → pulmonary hemorrhagic edema (opioid, poppins derivate).
• Cocaine → alveolar hemorrhages, cardiac arrhythmia, infarction, seizures, respiratory arrest.
• Methylphenidate → pulmonary emphysema.
• Amphetamine → myocarditis.
• Inhaled drugs → chronic bronchitis, metaplasia.
• Nasal inhalation (cocaine) → perforation of nasal septa, aspiration pneumonia, pyothorax, foreign body granulomas, pulmonary hypertension.
• Injected drugs (heroin) → foreign body granulomas → pulmonary hypertension, infective endocarditis of the right heart → septic pulmonary emboli.
• Other: interstitial pneumonia, lung infarction, asthma exacerbation, chronic obstructive pulmonary diseases.

Cocaine Injection

• Vasoconstriction
  • necrosis/perforation of the nasal septum
  • acute porphyria
  • intranasal warts
  • scleroderma
  • palpable purpura
  • Henoch-Schöenlein purpura
  • Churg- Strauss syndrome

Crack Cocaine Abuse

• Leads to pigment-laden macrophages and interstitial lymphocytic infiltrate because crack is insoluble in water -> process: cocaine hydrochloride in water + alkali (usually baking soda) -> heated and crystalizes.
  Vaporized at low temperatures and smoked.

Talcum-Induced Pneumoconiosis

• Related to inhalation of adulterated marijuana and methylphenidate use in intravenous drug abusers.

LUNG-RELATED ADVERSE DRUG-REACTIONS (ADR)

• IATROGENIC LUNG INJURY.
• 400 medications cause respiratory diseases (20 drugs in 1960s).
• Drug-induced pulmonary toxicity – about 3% ??? 5% of all patients receiving any drug; > 0.03% of all hospital deaths.
• less than 10% of patients receiving chemotherapy.
• Idiosyncratic reactions – more often than we know!!!!
• Lung injury is usually considered as “probable” or “possible.

LUNG-RELATED ADVERSE DRUG-REACTIONS (ADR)

• IATROGENIC LUNG INJURY (Drug-related toxicity).
  • Unspecific symptoms: dry cough, low-grade fever, dyspnea, wheezing, hypoxemia, chest pain, fatigue, allergic reaction, rash, arthralgia.
  • Serum: increased CD8+ lymphocytes and neutrophils + eosinophilsRx: alveolar/interstitial/mixed opacities with asymmetrical distribution, subpleural masses, pleural thickenning/effusion.
  • Function: decrease in the carbon monoxide diffusing capacity.
  • Bronchoalveolar lavage fluid: foamy macrophages ± eosinophils – indicator for drug use not toxicity!!!

LUNG-RELATED ADVERSE DRUG-REACTIONS

• Drug-induced interstitial lung disease.
• Bronchiolitis obliterans organizing pneumonia (BOOP).
• Interstitial edema, pneumocyte necrosis → interstitial pneumonia, lipid-laden macrophages in alveolar spaces, cytoplasmic lipid inclusion in pneumocytes, interstitial cells, endothelial cells, mononuclear cell interstitial infiltrate, interstitial fibrosis, proliferation of type 2 pneumocytes (± atypia, metaplasia), desquamative interstitial pneumonia, diffuse alveolar damage ± hyaline membranes, eosinophilic pneumonia, granulomatous lung disease, hypersensitivity pneumonia, organizing pneumonia.
• ALVEOLAR HEMORRHAGE IS RARE

Hypersensitivity Pneumonia

• Granulomas and mononuclear cell infiltrates.

BCNU-Associated Pulmonary Fibrosis

• Marked interstitial fibrosis.

Drug Reaction Examples

• Oxaliplatin + capecitabine induced liver/pancreas injury, myocardium

Pathology of the Respiratory System - Revisited

• Key Areas of Study:
  • Lesions of the upper respiratory tract (pp. 545-547)
  • Pathology of the lung
    • Disorders of the pulmonary air content: Atelectasis and respiratory distress syndrome of the adult and newborn (pp. 495-497, 278-279)
    • Obstructive lung diseases (pp. 498-499, 500-506)
    • Pulmonary infections: Pneumonias (pp. 519-525)
    • Injury by nontherapeutic toxic agents (drug abuse) (pp. 315-317)
    • Chronic interstitial lung diseases and smoking-related interstitial diseases (pp. 506-508; 514-515)
    • Lung tumors (pp. 537-544)
  • Pleural diseases (pp. 544-545)

INFLAMMATIONS (INFECTIONS) OF THE LUNG

• I. Non-specific inflammations
  • Pneumonia: bacterial inflammation, lobar pneumonia, bronchopneumonia.
  • Viral inflammation: interstitial pneumonia.
  • Pulmonary fibrosis.
  • Pneumoconioses.