Pathologie (Fach) / Respirationstrakt (Lektion)

6. SJ.

Diese Lektion wurde von estoffel erstellt.

Lektion lernen

zurück  |  weiter 1 / 1

• Pneumonia - Pathology Lobar pneumonia: - Classic (typical) pneumonia of an entire lobe- Primarily caused by pneumococci- Classic disease progression in stages→ Congestion (day 1): serous exudate in blood-rich lungs, numerous bacteria evident→ Red hepatization (days 2-3): exudate rich in fibrin and inflammatory cells with many bacteria still visible; lungs take on a liver-like texture. Lung loses some spongy quality→ Gray hepatization (days 4-7): erythrocytes are degraded but inflammatory cells persist; most bacteria have been destroyed by this stage. Lung is now firm→ Resolution (day 8 to week 4): fibrinolysis by enzymatic means and removal of the purulent exudate via productive cough Bronchopneumonia: mostly descending infection that affects the bronchioles and adjacent alveoli; usually involves the lower lobes or right middle lobe; manifests as typical pneumonia- Primarily caused by pneumococci and/or other streptococci Necrotizing bronchopneumonia (and pneumatocele) are caused by Staphylococcus aureus and are often preceded by an influenza infection. Interstitial pneumonia: interstitial inflammation, particularly caused by mycoplasma and viral infections; manifests as atypical pneumonia Miliary pneumonia: multiple small infiltrations caused by hematogenous dissemination (e.g., of tuberculosis)
• Lobärpneumonie 1. Intraalveoläre Entzündung 2. Lobärer Befall: Der ganze Lappen ist gleichmässig befallen. 3. Stadienhafter Ablaufa) Anschoppung: Aktive Blutstauung, seröses Exusat mit vereinzelten Leukozyten und Alveolarmakrophagen.b) Rote Hepatisation: Erythrozyten- und fibrinreiches Exsudat bei Blutstauung.c) Graue Hepatisation: Fibrinreiches Exsudat mit zunehmender Beimengung von Leukozyten.d) Gelbe Hepatisation: Reichlich, z.T. zerfallende, vervettende, segmentkernige Granulozyten. 4. Fibrinöse Begleitpleuritis: Die Oberfläche der Pleura visceralis zeigt eine fibrinreiche Exsudation mit Entzündungszellen.
• Asthma Allergic asthma (extrinsic asthma)- Cardinal risk factor: atopy- Environmental allergens: pollen (seasonal), dust mites, domestic animalsNonallergic asthma (intrinsic asthma)- Cold air- Physical exertion (exercise-induced asthma)- Gastroesophageal reflux disease (GERD): often exists concurrently with asthma - Chronic sinusitis or rhinitis- Medication: aspirin/NSAIDS (aspirin-induced asthma)- Irritant-induced asthma (e.g., from exposure to solvents, ozone, tobacco or wood smoke, cleaning agents) Pathophysiology:1. Bronchial hyperresponsiveness2. Bronchial inflammation3. Endobronchial obstruction caused by bronchospasm, mucosal edema, hypertrophy of smooth muscle cells Diagnostics:- Pulmonary function testing (spirometry) → ↓ FEV1, ↓ Tiffeneau index (FEV1/FVC ratio)- Methacholine challenge test- Chest x-ray- Pulse oximetry and blood gas analysis (ABG)- In allergic asthma: Antibody testing, IgE ↑, possibly eosinophilia, skin allergy tests- Sputum sample: Curschmann spirals, Charcot-Leyden crystals, and/or Creola bodies
• Asthma bronchiale 1. Hyperkrinie: Vermehrte Schleim in den Schleimhautdrüsen- Curschmann-Spiralen: Wirbelartig aufgebaute Schleimmassen 2. Histologische Zeichen der allergischen Genesea) Eosinophile Granulozytenb) Charcot-Leyden-Kristalle (Zerfall der eosinophilen Granulozyten)c) Verdickte Basalmembran 3. Hypertrophie der Bronchialmuskulatur 4. Plattenepithelmetaplasien der Bronchialschleimhaut
• Lung cancer - Second most common carcinoma; leading cause of cancer death (worldwide)- Peak incidence: 50-70 years- Sex: M > F (∼3:1)- Adenocarcinoma is an exception: M < F (∼1:6) Risk factors:- Nicotine: smoking causes approx. 90% of lung cancers- Occupational and environmental exposure to carcinogens: passive smoking, asbestos, arsenic, radon, uranium - Family history (genetic predisposition)- Scar tissue in the lungs (e.g., pulmonary fibrosis, history of tuberculosis)- Idiopathic: particularly adenocarcinoma Clinical features:- Cough (chronic or recently developed)- Hemoptysis- Progressive dyspnea- Chest pain Paraneoplastic symptoms:- General: cachexia, increased risk of thrombosis (and lung embolism!)- Dermatomyositis- Acanthosis nigricans- Hypercalcemia of malignancy (squamous cell carcinoma)- Gynecomastia (large cell carcinoma)- Hypertrophic osteoarthropathy - Nonbacterial verrucous endocarditis (adenocarcinoma)- SCLC: Cushing syndrome, SIADH, Lambert-Eaton syndrome, paraneoplastic cerebellar degeneration Classification:Small cell lung cancer: ∼15%Non-small cell lung cancer (NSCLC) approx. 85%- Adenocarcinoma: ~40%- Squamous cell carcinoma (SCC): 20-25%- Large cell carcinoma: 5-10% Subtypes:- Pancoast tumor: A peripheral lung carcinoma (predominantly NSCLC) that is located in the superior sulcus of the lung; often involves the cervical sympathetic nerves and brachial plexus.- Bronchioloalveolar carcinoma: Noninvasive subtype of adenocarcinoma (also known as adenocarcinoma in situ) Metastases: most commonly in the brain, liver, adrenal glands, or bones Diagnostics:- Chest x-ray and comparison to previous images- CT imaging- Assessment of lesion size and probability of malignancy (solid lesion ≥ 8 mm, irregular margins, spicules)- PET- Bronchoscopy and biopsy
• Adenocarcinoma of the lung ∼40% of all lung carcinomas.- Most common type of lung cancer overall and in women- Most common lung cancer in non-smokers Associated mutations: EGFR, ALK Location: Peripheral- Noninvasive subtype: bronchioloalveolar carcinoma Paraneoplastic symptoms:- Hypertrophic osteoarthropathy - Hypercoagulability and thrombophlebitis migrans- Nonbacterial verrucous endocarditis Pathology:- Glandular tumor- Mucin-producing cells (Alcian-blue/PAS staining)- Subtypes of adenocarcinomas are classified according to the growth pattern (e.g., lepidic, papillary, acinar, solid)- Detection of EGFR mutations and ALK translocations (immunohistochemistry or FISH) - Immunohistochemistry: expression of napsin A and TTF-1 Targeted therapies:- EGFR inhibitors (e.g., gefitinib, erlotinib)- ALK tyrosine kinase inhibitors (e.g., crizotinib)
• Small cell lung cancer Pulmonary neuroendocrine tumor; associated with several paraneoplastic syndromes Frequency: ∼15% Strong correlation with cigarette smoking Location: Central Paraneoplastic symptoms:- Cushing syndrome- Syndrome of inappropriate antidiuretic hormone secretion (SIADH)- Lambert-Eaton syndrome- Paraneoplastic cerebellar degeneration- Peripheral neuropathy Pathology:- Kulchitsky cells: Small, dark blue neuroendocrine cells with hyperchromatic nuclei and scarce cytoplasm. - Hyperchromatic nuclei (salt and pepper appearance) is a marker for rapid growth and high metabolic activity- Rapid growth pattern- Immunohistochemistry: expression of chromogranin A, neuron-specific enolase, synaptophysin, CK18, and CK7 Treatment:- Limited disease (20%): Curative→ Polychemotherapy + radiation therapy- Extensive disease (75%): Palliative→ Polychemotherapy→ Radiation therapy if the patient responds well to initial chemotherapy→ Prophylactic cranial irradiation if the patient responds to the initial chemotherapy treatmentPolychemotherapy = cisplatin and etoposide Limited disease 5-year survival: 12-15%Extended disease 5-year survival: 2% 
• Squamous cell carcinoma of the lung 20-25% Strong association with smoking! Location: Central airwaysDirect spread to hilar lymph nodes Paraneoplastic syndrome: Hypercalcemia of malignancy Pathology:- Solid, epithelial tumor- Subtypes: keratinizing, nonkeratinizing, basaloid- Histology: intercellular bridges (desmosomes), keratin pearls- Immunohistochemistry: expression of cytokeratin subtypes CK5 and CK6, p40
• Differential diagnosis of pulmonary nodules Pulmonary lung cancer: SCLC/NSCLC- Central or peripheral nodule- Irregular margins and/or spicules- Tumor size typically > 2 cm- No calcifications  Lung metastases: Breast cancer, colorectal cancer, renal cell carcinoma, prostate cancer, bladder cancer, melanoma- More commonly multiple pulmonary nodules- Nodule size typically > 1 cm Pulmonary neuroendocrine tumor: Carcinoid bronchial carcinoma- Round or oval opacities- Size typically 2–5 cm- Hilar or perihilar mass Benign tumors: Hamartomas- “Popcorn” calcifications- Round, well-circumscribed nodules, lobulated by respiratory epithelium- Fat, fibromyxoid tissue, sometimes smooth muscle- Size typically 1–3 cm- 90% are peripheral, 10% are endobronchial Infectious granulomas:- Tuberculosis- Nontuberculous mycobacteria- Histoplasmosis- Round, well-defined, calcified nodule Inflammatory conditions:- Sarcoidosis- Granulomatosis with polyangiitis (Wegener granulomatosis)- Multiple bilateral cavitating nodular lesions
• Mesothelioma - M > F (3:1)- Age range: ∼40–70 years Etiology: secondary to asbestos exposure Localization: Most commonly manifests as pleural mesothelioma; rarely the peritoneal mesothelioma; very rarely the pericardial mesothelioma Clinical findings:- Dyspnea and nonpleuritic chest pain (most common)- Fever, sweats, weight loss, fatigue- Features of a pleural effusion: dull percussion, absent or reduced breath sounds on affected side Diagnosis:- Pleurocentesis: bloody (exudative) pleural effusion- Imaging (Chest x-ray and CT): Multiple nodular, pleural lesions (pleural thickening)- Ipsilateral hemothorax- Reduced size of ipsilateral lung fields- Obliteration of the diaphragm- Laparoscopy, thoracoscopy, and pleuroscopy with stained biopsy: mesothelioma cells and psammoma bodies It is important to differentiate mesothelioma from adenocarcinoma.- Immunohistochemistry: Mesothelin, serum mesothelin-related protein (SMRP), calretinin, cytokeratin 5/6, and vimentin (adenocarcinomas are positive for CEA)- Microvilli in mesothelioma are long and slender; they are short and stubby in adenocarcinoma Classification: Epithelial / sarcomatous / biphasic Treatment: Radiation, with or without chemotherapy (cisplatin and pemetrexed). - Surgery (pleurectomy or pneumonectomy) could be indicated in cases with severely impaired pulmonary function Prognosis: Poor, with a mean survival time of ∼1 year.
• Bronchiectasis Irreversible and abnormal dilation in the bronchial tree that results in COPD. Etiology:- Pulmonary infections, especially chronic infections - Disorders of secretion clearance or mucous plugging→ Cystic fibrosis → Primary ciliary dyskinesia→ Allergic bronchopulmonary aspergillosis (ABPA)- Bronchial narrowing or other forms of obstruction→ COPD→ Aspiration→ Tumors- Immunodeficiency (e.g., common variable immunodeficiency, hypogammaglobulinemia, HIV)  Clinical features:- Chronic productive cough (lasting months to years) - Copious mucopurulent sputum- Hemoptysis- Dyspnea- Digital clubbing Diagnosis:- Chest x-ray (initial test)- High-resolution computer tomography (HRCT): confirmatory test- Pulmonary function tests: findings consistent with obstructive pulmonary disease- Bronchoscopy: to visualize tumors, foreign bodies, or other lesions Treatment:- Antibiotics for exacerbations- Bronchopulmonary hygiene and chest physiotherapy: Postural drainage- Vaccinations (i.e. seasonal influenza vaccine, pneumococcal vaccine)
• Emphysema Form of COPD characterized by permanent dilatation of pulmonary air spaces caused by the destruction of the alveolar walls. Classification:Panlobular emphysema (panacinar emphysema):- Rare- Associated with α1-antitrypsin deficiency- Usually affects the lower lobeCentrilobular emphysema (centriacinar emphysema):- Common- Classically seen in smokers- Usually affects the upper lobeParaseptal emphysema:- Affects distal alveoli, near the intralobular septae- Can rupture and cause pneumothoraxBullous emphysema- Affects lung apexes- Can rupture and cause pneumothorax Clinical features:- Chronic cough with expectoration (expectoration typically occurs in the morning)- Dyspnea: initially only on exertion, later continuously- Tachycardia and tachypnea- Weight loss and cachexia- In cases of advanced COPD and/or cor pulmonale→Congested neck veins→ Barrel chest→ Use of accessory respiratory muscles due to diaphragmatic dysfunction→ Peripheral edema (most often ankle edema) Diagnostics:- Spirometry and/or body plethysmography: FEV1/FVC < 70% (Tiffeneau-Pinelli index)- Diffusing capacity for carbon monoxide (DLCO): decreased (normal in chronic bronchitis)- Blood gas analysis (BGA) and pulse oximetry Treatment:- Cessation of smoking- Vaccinations- Pulmonary rehabillitation- Bronchodilators: either parasympatholytics or β2-agonists→ Long-acting parasympatholytics: tiotropium bromide→ Long-acting β2-agonists: salmeterol, formoterol→ Short-acting parasympatholytics: ipratropium bromide→ Short-acting β2-agonists: salbutamol, fenoterol- Inhaled corticosteroids: budesonide, fluticasone, beclomethasone- PDE type 4 inhibitors (PDE = phosphodiesterase): roflumilast
• Pulmonary embolism Etiology:- Deep vein thrombosis (most common cause)- Risk factors: obesity, hypomobility or immobility, malignancy, pregnancy, dehydration, hypercoagulability, use of contraceptives, previous DVT - Fat embolism during major surgical interventions (e.g., endoprosthesis replacement, osteosynthesis)- Others: air embolism, amniotic fluid embolism, cement embolism Clinical features:- Acute onset of symptoms, often triggered by a specific event (e.g., on rising in the morning, sudden physical strain/exercise)- Dyspnea and tachypnea (> 50% of cases)- Sudden chest pain (∼50% of cases), worse with inspiration- Cough and hemoptysis- Tachycardia (∼25% of cases), hypotension- Jugular venous distension- Low-grade fever- Symptoms of DVT: unilaterally painful leg swelling Diagnostics:- Hemodynamically stable with Wells score > 4 → CTA for definitive diagnosis→ Unless strongly contraindicated, administer immediate anticoagulation with unfractionated heparin before conducting a CTA→ If too unstable for CTA → perform bedside echocardiography obtain a presumptive diagnosis of PE (right ventricle enlargement/hypokinesis or visualization of clot) prior to empiric thrombolysis.- In patients with a Wells score ≤ 4 → measure D-dimer levels (+ ABG evaluation + CXR)
• Pneumonie 1. Stadium der Anschoppung (1. Tag): Die Lunge ist flüssigkeitsreich, weich und von düsterroter Farbe infolge einer ausgeprägten Blutstauung in den Alveolarkapillaren. 2. Rote Hepatisation (2. bis 3. Tag): Beginnt mit Fibrinausschwitzungen, die der Lunge eine leberartige Konsistenz verleihen. Durch die noch bestehende Blutfülle zeigt die Schnittfläche eine rote Farbe. 3. Graue Hepatisation (4. bis 6. Tag): Während die Blutfülle zurückgeht, nehmen die Fibrinausschwitzungen zu, sodass die Schnittfläche jetzt von grauer Farbe ist. 4. Gelbe Hepatisation (7. bis 8. Tag): Durch einen massiven Austritt von segmentkernigen Leukozyten, die anschliessend pyknotisch werden, nimmt die Lungenschnittfläche eine gelbe Farbe an. Die feste Konsistenz bleibt bestehen. Komplikationen: - Begleitpleuritis → Pleuraempyem- Chronisch karnifizierende Pneumonie- Septikopyämie
• Interstitial lung disease Etiology:- Idiopathic pulmonary fibrosis (IPF): most common- Desquamative interstitial pneumonia (DIP)- Nonspecific interstitial pneumonia (NSIP)- Cryptogenic organizing pneumonia (COP)- Acute interstitial pneumonia (AIP)- Pneumoconioses: Asbestosis, Silicosis- Radiation- Pharmacologic: Bleomycin, methotrexate, busulfan, amiodarone, nitrofurantoin- Granulomatous interstitial lung disease: Sarcoidosis, pulmonary Langerhans cell histiocytosis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis - Infectious diseases (eg, tuberculosis)- Connective tissue disease: Rheumatoid arthritis, scleroderma, systemic lupus erythematosus, and mixed connective tissue disease Clinical features:- Dyspnea- Persistent nonproductive cough- Fatigue- Later stages of disease: digital clubbing Diagnostics:- CT or HR-CT: Irregular thickening of the interlobular septa, honeycombing, and bronchiectasis
• Neonatal respiratory distress syndrome Lung disorder in infants that is caused by a deficiency of pulmonary surfactant. - 1% of all newborns- 10% of all preterm babies Etiology:- Impaired synthesis and secretion of surfactantRisk factors:- Prematurity- Genetic predisposition- Scheduled cesarean section- Maternal diabetes mellitus- Hydrops fetalis- Multifetal pregnancies Clinical features:- History of premature birth- Onset of symptoms: usually presents immediately after birth- Signs of increased breathing effort: → Tachypnea→ Nasal flaring → Subcostal/intercostal and jugular retractions- Typical expiratory “grunting”- Cyanosis due to peripheral hypoxic vasoconstriction Diagnostics:- Chest x-ray: diffuse, fine, reticulogranular (ground-glass) densities, with low lung volumes and air bronchograms- Blood gas analysis: Hypoxia with respiratory acidosis- Markers of fetal lung immaturity: Lecithin-sphingomyelin ratio < 1.5, foam stability index < 0.48, low surfactant-albumin ratio Microscopic findings:- Hyaline membranes lining the alveoli with engorged and congested capillary vessels→ Composed of fibrin, cellular debris, and red blood cells→ Appear as eosinophilic, amorphous material lining the alveolar surface Treatment:- Ventilation: Nasal CPAP with a PEEP of 3-8 cm H2O- Endotracheal administration of artificial surfactant within 2 hours postpartum- Supportive measures: IV fluid replacement; stabilization of blood sugar levels and electrolytes
• Acute respiratory distress syndrome Severe inflammatory reaction of the lungs to pulmonary damage.  Etiology:- Sepsis (most common cause)- Shock- Acute Pancreatitis- Hematopoietic stem cell transplantation- Medication (e.g., salicylic acid, tricyclic antidepressants, bleomycin)- Recreational drug overdose (e.g., cocaine) Pathophysiology: - Tissue damage (pulmonary or extrapulmonary) → release of inflammatory mediators (e.g., interleukin-1) → inflammatory reaction → injury to alveolar capillaries and endothelial cells leading to:→ Excess fluid in interstitium and on alveolar surface → pulmonary edema→ Exudation of neutrophils and protein-rich fluid (hyaline membrane) into the alveolar space → diffuse alveolar damage (DAD)
• Aspergillosis Pathogen: Aspergillus fumigatus, Aspergillus flavus Risk factors:- Destructive pulmonary pathology (e.g., scar tissue/lung cavities from tuberculosis, COPD, emphysema)- Severe immunosuppression (e.g., HIV, neutropenia) → invasive aspergillosis- Pre-existing bronchopulmonary conditions (e.g., asthma or cystic fibrosis) → ABPA Clinical features:- Allergic bronchopulmonary aspergillosis (ABPA)→ Asthmatic symptoms (e.g., shortness of breath, wheezing)→ Productive cough with brown bronchial mucous casts→ Sinusitis without tissue infiltration- Chronic pulmonary aspergillosis→ Aspergilloma: opportunistic infection of a pre-existing cavitary lesion (e.g. from previous tuberculosis)→ Weight loss, fatigue→ Cough, hemoptysis, shortness of breath - Invasive aspergillosis→ Pulmonary aspergillosis → Dry cough, hemoptysis, fever, pleuritic chest pain, septic shock→ Aspergillus sinusitis with invasion of the surrounding tissue→ Invasion into the orbit → reduction of visual acuity, painful exophthalmos, chemosis→ Invasion into the skull → CNS involvement, venous sinus thrombosis Diagnostics:- Imaging- PAS or Gomori methenamine silver stain: septate hyphae branching dichotomously at 45°- Positive Galactomannan antigen test Treatment:- ABPA: Glucocorticoids, consider adding itraconazole- Pulmonary aspergillosis: Surgical resection (e.g., lobectomy) + antifungals (e.g., oral itraconazole or voriconazole)- Invasive aspergillosis: IV voriconazole
• Cystic fibrosis Autosomal recessive disorder caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.- The most common mutation is ∆F508 on chromosome 7 (absence of the amino acid phenylalanine [F] in position 508 of the protein)- Mutated CFTR gene → misfolded protein → retained protein in RER that is unable to reach the cell membrane → defective chloride channel → inability to transport intracellular chloride ions across the membrane → exocrine glands (e.g., sweat, pancreas, salivary glands) produce hyperviscous secretions → accumulation of secretions and blockage of exocrine glands → chronic inflammation → organ damage Clinical features:- Recurrent pulmonary infections (eg, S aureus in early infancy, P aeruginosa in adolescence), chronic bronchitis and bronchiectasis- Pancreatic insufficiency, malabsorption with steatorrhea, fat-soluble vitamin deficiencies (A, D, E, K), biliary cirrhosis, liver disease. Meconium ileus in newborns.- Infertility in men (absence of vas deferens, spermatogenesis may be unaffected) and subfertility in women (amenorrhea, abnormally thick cervical mucus).- Nasal polyps, clubbing of nails Diagnostics:-? Newborn screening: Immunoreactive trypsinogen- Best initial test is the sweat chloride test→ Chloride levels > 60 mmol/L on two or more occasion- CFTR mutation Treatment:- Chest physiotherapy, albuterol, aerosolized dornase alfa (DNase), and hypertonic saline facilitate mucus clearance. Azithromycin used as anti-inflammatory agent. Ibuprofen slows disease progression.- In patients with Phe508 deletion: combination of lumacaftor (corrects misfolded proteins and improves their transport to cell surface) and ivacaftor (opens Cl– channels ?improved chloride transport).

zurück  |  weiter 1 / 1