Atelectasis of the lung, Acute Lung injury, and Diseases of Vascular Origin Disease Atelectasis Obstructive Atelectasis (Resorption) Compression Atelectasis Contraction Atelectasis Atelectasis due to loss of surfactant Pathogenesis - Incomplete expansion or collapse of previously inflated lung, producing areas of relatively airless pulmonary parenchyma - Can occur at birth or anytime afterwards - Reversible, since collapsed lung can be reinflated o Exception, scarring (contraction atelectasis - Complete obstruction of an airway causes resorption of oxygen distally through the pores of Kohn in alveoli - Due to excessive bronchial secretions and mucous plugging (bronchial asthma, chonic bronchitis, post-op complication) - Tumors incomplete obstruction and localized emphysema Mediastinum shifts toward lung - Filled Pleural cavity (fluid, tumor, blood clot, air) partial or complete o HF or neoplastic effusion fluid compresses the lung o Pneumothorax Air compresses the lung - Abnormally elevated diaphragm: basal atelectasis o Peritonitis, subdiaphragmatic abscess or seriously ill post-op Mediastinum shifts away lung - Local or generalized fibrotic changes o Pleura / Lungs prevent expansion - Ex. Respiratory Distress Syndrome (RDS) in Infants - Loss of surfactant Surfactant normally prevents collapse ©2010 Mark Tuttle Clinical - Labs/Histology - Fever - Ipsilateral elevation of the diaphragm - Dyspnea - Usually within 24 hours of collapse - Absent breath sounds - - Ground-glass appearance on X-ray Acute Lung Injury: Pulmonary Edema • Pulmonary congestion + edema • Adult Respiratory Distress Syndrome (Diffuse alveolar damage b/c can be children too) 1. Hemodynamic edema(transudate) 2. Edema from Microvascular Injury (exudate) - Hydrostatic pressure ↑ - Infections: pneumonia, septicemia - Heavy, wet lungs, o Left sided HF (common) - Inhaled gases: oxygen, smoke frothy blood tinged o Volume Overload - Aspiration: gastric contents, near-drowning fluid o Pulmonary vein obstruction - Drugs/chemicals: chemotherapeutic agents - Fluid accumulates - Oncotic pressure ↓ (less common) o Bleomycin: edema & fibrosis Short term Long-term in the lower lobes o Hypoalbuminemia o Amphotericin B Microscopic changes where hydrostatic o Nephrotic syndrome o Heroi - Intraalveolar granular eosinophilic precipitate pressure is greater o Liver disease o Kerosine - Alveolar microhemorrhages and hemosiderin- Changes lead to o Protein-losing enteropathies o Paraquat (herbicide) laden macrophages (“heart-failure cells”) present impaired function - Lymphatic Obstruction - Shock in chronic cases (interstitial edema) - Trauma - With long-standing chronic passive congestion and predisposes - Transfusion-related (TRALI) (e.g. mitral stenosis – fish mouth from RF), lungs one to infections 3. Edema of undetermined origin become visibly brown. firm (hemosiderin-laden (intraalveolar - High Altitude (HAPE) – High altitude pulmonary edema macrophages and interstitial fibrosis) edema) - Neurogenic (CNS trauma) termed “brown induration” Adult Respiratory Infection Chemical Injury - Rapid onset of: Acute Stage Distress Syndrome Sepsis (40% cases) Heroin or methadone o Severe life-threatening respiratory insuffic. - Increased capillary permeability produces (ARDS, Diffuse Diffuse pulmonary Acetyaslicyclic acid o Cyanosis interstitial and then intra-alveolar edema Alveolar Damage infections Barbituate overdose o Severe arterial hypoxemia refractory to - Interstitial inflammation DAD) Gastric aspiration Paraquat (herbicide) oxygen therapy - Hyaline membranes composed of fibrin rich (30% cases) o “White out” on X-ray - bilateral fluid, cytoplasmic and lipid remnants of Noncardiogenic Inhaled Irritants - Severe pulmonary edema necrotic epithelial cells pulmonary edema Physical Injury Oxygen toxicity - Frequently progresses to multisystem failure Organizing stage resulting from acute Mechanical Smoke Pathogenesis - Resolution is unusual. Instead, the fibrin alveolar-capillary trauma(head ) Irritant gases and - Diffuse damage to alveolar capillary walls exudate organizes damage (20% cases) chemicals - Most common: alveolar capillary endothelium - Hyperplasia of type II pneumocyte continues Pulmonary - Less common: injury to alveolar epithelium – attempt at repair and resolution Clinical Course contusions Hematologic - Increased vascular permeability ↑ - Interstitial inflammation and fibrosis - 150,000 cases/year Near-drowning Multiple transfusions Alveolar flooding, rich in fibrin, deposit in wall - Intra-alveolar fibrosis in USA Fractures with fat DIC - Analogous to crescenteric glomerulonephritis - Honeycomb lung - 60% mortality embolism - Loss of diffusion capacity Superimposed bacterial infx: in fatal cases - Severe dyspnea + Burns Pancreatitis - Widespread surfactant abnormalities due to Diffuse Alveolar Damage (DAD) tachypnea Ionizing radiation damage of Type II Pneumocytes Atelectasis Hyaline membrane - O2 transport dmgd - Hypoxemia Uremia - Resolve in 1st week unresponsive to O2 Hypersensitivity - If survive > 1week, therapy Organic solvents Cardiopulm bypass Honeycomb inflammation + fibros - PaO2 < 50mmHg Drugs Lung compliance ↓ - Respiratory therapy V/Q mismatch - Need high O2 to treat but O2 toxicity Diseases of Vascular Origin: Pulmonary embolisum, hemorrhage, infarction. Pulmonary HTN, vascular sclerosis, Diffuse pulmonary hemorrhage (Goodpasture, idopath) Disease Pathogenesis Clinical Labs/Histology Pulmonary Embolism - Blood clot that occlude the large None (~60-80% are clinically silent) Embolus: pulmonary arteries - Too small of emboli - Red cells, platelets and fibrin fill arterial Large - Source: DVT in legs (most common) Hemorrhage (~10-15%) lumen adhering to endothelial surface - Chest pain - Predisposing factors: - Tissue viability sustained by collateral blood flow - May dissolve or organize and recanalize - Dyspnea o Immobilization (ex. hospital, flight) - Transient chest pain & cough Hemorrhage: - Shock o Hypercoagulable States Infarction (10%) – less likely b/c collateral circul. - Blood in alveoli and interstitium - Fever (Factor V bleeder, Contraception – - Due to inadequate collateral blood flow; often - Preserved architecture - Elevated enzyme, estrogen, Malignancy [Trousseau’s]) coexisting heart and lung disease is present Infarct: Acute R-HF (cor pulm.), CV collapse sudden death - Usually wedge-shaped and peripheral, with LDH3 ↑ Treatment - Due to obstruction of pulmonary vasculature embolus at apex mimic MI - Difficult problem: prophylaxis - Patients have electromechanical dissociation - Apex points to hilum - Early post-surgical ambulation Pulmonary hypertension - ¾ infarcts in lower lobe Small - Elastic stockings, leg exercises - Multiple emboli over time; can cause chronic Acute (recent) infarct - Transient chest Anticoagulation for high-risk ppl right heart strain (right ventricular hypertrophy) - Coagulative necrosis with hemorrhage pain or cough- Filter in inferior vena cava Second embolus (30%) (ie. red infarct) normal CVS - Overlying pleura with fibrinous pleuritis - Dyspnea - Post-morten clot: free, unattached Seen in most cases Remote (old) infarct - Tachypnea - Pre-morten clot: lines of Zahn, on vessel - Wheezing from THXA2 from platelets - Inflammatory response followed by - Chest pain - Fever regeneration and fibrosis (scar) - Cough, hemoptysis - Pleural friction rub - Often hemosiderin in macrophagesHF cells – infarcts with Special types of Emboli compromised Pulmonary Infarct Fat embolism: Air embolism: bronchial - Multiple in > 50% - Most common form of clinically - Trauma, surgery, intravenous injections, circulation - Lower lobes: 2/3 significant embolism second to obstetrical procedures, criminal abortion - Wedge shaped thromboembolism May cause sudden death frothy blood is Diagnosis - Base peripheral - Occurs generally as a result of fracture present in the right ventricle and pulmonary - Spiral CT - Apex toward hilum of a long bone, most typically the femur artery at autopsy angiography - Histological examination shows fat - On histological examination, empty spaces - Most definitive globules in the capillaries and small resembling fat emboli are seen technique, but Saddle Embolus vessels of the lung Embolic carcinomatosis: dangerous for the Septic embolism: - Carcinomas (breast, stomach and lung) invade patient - Infected fragments of venous thrombi or blood vessels, disseminate and occlude - D-dimer level tricuspid valve vegetations (endocarditis) pulmonary arteries - “Septic infarct” (neutrophils and Amniotic fluid embolism: organisms) can convert to abscess - Usually at time of delivery; can cause shock and Bone marrow embolism: diffuse alveolar damage in severe cases - CPR with chest compressions leading to rib fractures Starch or talc particles: - Contained in drug injected by addicts Disease Pulmonary Hypertension When mean pulmonary pressure reaches ¼ systemic Pathogenesis - Primary (Idiopathic) – rare o Females: 24-40yrs; sometimes young o Dyspnea, fatigue (hypoxia), common o Some patients have angina o Right ventricular hypertrophy o 80% die 2-5 years of Cor Pulmonale o Often w/emboli, pneumonia - Secondary: Structural conditions which increase pulmonary blood flow, vascular resistance, or L heart resistance o Chronic obstructive, insterstitial lung diseases o Antecedent congenital or acquired heart disease (ex. TOF) o Recurrent thromboemboli o Autoimmune disorders Diffuse Pulmonary Hemorrhage Syndromes Goodpasture - Anti-Basement Membrane Antibodies Syndrome - Simultaneous renal, pulmonary disease - Proliferative rapidly progressive glomerulonephritis - Necrotizing hemorrhagic interstitial pneumonitis Idiopathic Pulmonary - Degeneration and hyperplasia of Hemosiderosis alveolar epithelial cells - Cause unknown Vasculitis-associated hemorrhage - Hypersensitivity angiitis - Wegener’s Granulomatosis - Lupus erythematosus (SLE) Clinical - Role of BMPR2 (Bone morphogenic prot) Surface protein family TGF-β Binds to cytokines o Embryogenesis o Cell proliferation & differentiation o Apoptosis - BMPR2 inhibition of proliferation - If mutated proliferation of sm. mm. o 50% of familial 1° pulmonary HTN o 26% of sporadic cases o 2q33 locus association Morphology Atheromatous plaques - Main elastic arteries Medial hypertrophy, intimal proliferation, fibrosis - Small arteries and arterioles Plexogenic pulmonary arteriopathy - Capillary tuft formation (“plexiform lesion”) - Indicates severe and irreversible hypertension - Males > Females; most cases in teens, 20s - Patients generally present with hemoptysis, focal lung consolidations and renal failure. - Uremia common cause of death - Trigger, initiating antibody is unknown. - Viruses, smoking and exposure to hydrocarbons (dry cleaning industry) may be cofactors - Treatment – immunosuppressants and plasmapheresis - Cough, hemoptysis, anemia, weight loss - Children and young adults - Labs/Histology Mainly arterioles, small arteries Medial thickness, intimal fibrosis, narrow lumen - Immunofluorescence shows linear deposits of immunoglobulins and complement on the glomerular BM and in the alveolar septa - Hemosiderin filled macrophages in alveoli and hemosiderin in alveolar septa o DDx from HF cells HF cells not in septa - Capillary dilatation and pulmonary fibrosis -