Obstructive Lung Diseases PDF

Obstructive Lung Diseases Prof Dr Sergülen Dervişoğlu  Learning objectives By the end of this course, students should be able to understand the terms of COPD Learns definition of obstructive pulmonary disease and its subtypes Understands pathogenetic mechanisms and clinical...

Obstructive Lung Diseases Prof Dr Sergülen Dervişoğlu  Learning objectives By the end of this course, students should be able to understand the terms of COPD Learns definition of obstructive pulmonary disease and its subtypes Understands pathogenetic mechanisms and clinical findings of COPD Understands bronchitis and its pathological findings Describes bronchiectasia subtypes both macroscopically and microspcopically and list its’ complications Explains the clinical, pathological findings and immunopathogenesis of bronchial asthma. Explains the definition of emphysema, its pathogenesis, subtypes according to causes and morphological features. Obstructive versus Restrictive Pulmonary Disease Obstructive (airway disease); an increase in resistance to airflow owing to partial or complete obstruction in any level Emphysema Chronic bronchitis (COPD) bronchiectasis asthma Restrictive; reduced expansion of lung parenchyma, with decreased lung capacity Chest wall disorders (Normal lung) neuromuscular disorders*polio, severe obesity, kyphoscoliosis acute or chronic interstitial and infiltrative disease ( pneumoconiosis / interstitial fibrosis) Disorders Associated with Airflow Obstruction: The Spectrum of Chronic Obstructive Pulmonary Disease Major Pathologic Clinical Term Anatomic Site Changes Etiology Signs/Symptoms Chronic bronchitis Bronchus Mucous gland Tobacco smoke, air Cough, sputum hyperplasia, pollutants production hypersecretion Bronchiectasis Bronchus Airway dilation and Persistent or severe Cough, purulent scarring infections sputum, fever Asthma Bronchus Smooth muscle Immunologic or Episodic wheezing, hyperplasia, excess undefined causes cough, dyspnea mucus, inflammation Emphysema Acinus Airspace Tobacco smoke Dyspnea enlargement; wall destruction Small airway Bronchiole Inflammatory Tobacco smoke, air Cough, dyspnea disease,* scarring/obliteration pollutants, bronchiolitis miscellaneous  Clinical features of COPD They are asymptomatic in early stages (because of pulmonary reserve) FEV1:FVC ratio is decreased Total lung capacity and residual volume are often increased as a result of trapping in the distended air spaces In the later phase COPD patients presents with spectrum of symptoms which are designated type A and type B Clinical features of COPD Type A (Pink puffer) Chronic cough Progressive dyspnea, wheezing Hyperventilate Sit hunched forward (to bring accessory respiratory muscles into action) Mouth open, nostrils dilated Lungs are over inflated ( increase in anteriopost. diameter of chest = barrel chest Flattened diaphragm on X-ray Oxygenation of blood is normal (hyperventilation) Clinical features Type B (Blue bloater) of COPD They have marked obstructive bronchitis and can not ventilate Decreased oxygenenation of blood (cyanosis) Arterial CO2 increased Changes microvasculature of lung paranchyma ⃗ PH ⃗ RV hypertrophy and failure ⃗ Corpulmonale ⃗ peripheral edema (blue bloater) Chronic hypercapnia; the respiratory center becomes insensitive to the increased CO2 stimulus and is driven by hypoxemia Administration of O2 in these patients can remove the resp. Center drive and cause CO2 retention and death “CO2 narcosis”  Chronic Bronchitis Pathogenesis: 5-10 times more common in heavy cigarette smokers Cigarette smoking acts as local irritant ⃗ hypertrophy of bronchial mucous glands ⃗ inreased in mucous cells ⃗ hypersecretion of mucus ⃗ neutrophils (🡩) Sulfur dioxide and oxidates of nitrogen are other inhaled irritants Hypersecretion of mucus increases the susceptibility to bacterial infection (H.influenza, pneumococcus, Strep.)  Chronic bronchitis Persistent productive cough for 2 years at least 3 consecutive months Simple chr. Bronchitis**no airway obstruction Mucoid sputum Secondary infections----chr. Mucopurulent bronchitis Hyperresponsive airways***intermittent asthma****chr. Asthmatic bronchitis Small population/pulm. Funciton test---chr. Obstructive bronchitis Chronic Obstructive Bronchitis Clinically persistent presence of increased bronchial mucus secretion, chronic cough productive of mucoid sputum Microscopic changes: hypertrophy bronchial wall mucous glands ass. w. Chronic inf -and fibrous replacement of muscular walls of small bronchioles Reid Index: the ratio of mucous gland thickness / bronchial wall thicknes = 0.5 (is increased) Fibrotic bronchioles tend to collapse in expiration (under the influence of the positive intrathorasic pressure, resulting in ventilatory obstruction in expiration) Bronşit  ▪ Normally bronchial wall gland thickness is half of the Epithelial-cartilag e distance ▪ If this ratio ↗ objective finding of chr. bronchitis REID INDEX bc < ad/2 = chr bronchitis Chronic Bronchitis  Respiratuar Bronşiyolit ✔ ✔ Smokers ✔Macrophages with brown pigment in Res. Bronchioles ✔ Goblet cell metaplasia ✔ Peribronchioler fibrosis ✔ Narrowing of the air ways  Complications Squamous Kronik Bronşit metaplasia ✔ Mucus gland Hyperplasia ✔ cartilage and smooth muscle cell 🞴 ✔ fibrosis of bronchial wall ✔ Bronchiectasis  Bronchiectasis is abnormal and irreversible dilatation of bronchial tree prox to the terminal bronchioles (in contrast to emphysema which involves the bronchial tree distal to the terminal bronchioles) Etiol: Chronic infection resulting paranchymal destruction fibrosis abnormal permanant dilatation of damaged bronchi usually bilaterally, dilatations long, tubelike enlargements (cylindroid), fusiform, saccular  Permanent dilatation Bronchi and bronchioles Destruction of muscle and elastic tissue Chronic necrotizing infection Not a primary disease Secondary to persisting infection and obstruction  Bronchiectasis Causes: Long standing bronchial obstruction Bronchial tumors, stenosis stagnation of mucus is followed by bronchopneumonia, mucus impact Atopic asthma and chronic bronchitis Mucoviscidosis (fibrocystic D. Of pancreas) (Mucus is abnormally thick) Cystic fibrosis Bronchopneumonia Necrotizing type****---measles,whooping cough, influenza immundeficiency Kartagener Syndrome: Cong. Defect in ciliary motions caused by autosomal recessive disorder ⃗ bronchopneumonia ⃗ bronchiectasis absence of frontal sinuses in male; loss of sperm motility and infertility dextracardia Intralobar sequestration  Bronşiyektazi Saccular cylindirical  Mostly lower lobes Bronşiyektazi and bilateral Bronchiectasis  Complications of bronchiectasis sonuç ve komplikasyonları Cor-pulmonale Repeated inf.; Pyemia-sepsis Pneumonia with abscess Pyogenic pleuritis Metastatic abcesses (brain ) ‘clubbing of the fingers’ Secondary Amyloidosis  Bronchial asthma Acute narrowing of bronchioles due to smooth muscle contraction (Bronchospasm) Obstr. of air flow-maximal expiration-high picthed wheeze Expiration is prolonged  Astım Heredity (exstrinsic asthma) Emotional stress Cold weather intrensic asthma Excersize Endocrine factors 30-60 minutes  Immun pathway🞴 CD4+ TH2 cell control IL-4 ve IL-5,IL13 release 🞴 Eosinophil fonc + release of inflammatory mediators (histamine, prostaglandin, leukotrien, Bradykinin) PAF, Mast cell triptase, TNF Non-immun pathway ?? CD4+ TH2 cells (autonomic system)🞴 vagal system stimulation (α Adrenerjik🞴, β adrenerjik🞴) 🞴 Reflex bronchospasm (A) Acute phase first 30-60 mn (B) late phase following 4-8 hr Bronchial wall; Smooth muscle cell contraction Eosinophil increase Mucosal vasodilatation Mucus hypersecretion  Asthma – Histology: nonspesific – Inspissation of mucus leads to bronchiolar obstruction and focal collaps of alveoli – Mild inflammation, edema – Episodic attacks of dyspnea and wheezing – Tx;Bronchodilator (theophyline, epinephrine,ß-adrenergics,corticosteoids Sputum;scanty, thick, viscous, forming casts of bronchioles(Curshmann’s spirales) Charcot leyden crystals (formed from degraded eosinophils)  Status asthmaticus: acute but long duration crisis Bronhcodilatators+ corticosteroid Frequent and extended attacks hypercapnia, asidosis , hypoxia ---- death  Emphysema Abnormal permanant enlargement of the airspaces distal to the terminal bronchiole, accomp. by destruction of their walls Not overinflation ( compansatory) Anatomic distribution: Centriaciner /centrilobular(90%) central or prox. parts of acini Panacinar; acini uniformly enlarged,( α1-AT) Paraseptal; distal acini Irregular Other types Bullous emphysema İntertitial emphysema  Irreversible damage of terminal airways; Irreversble dilatation of Terminal respiratory unite Autopsies 50% cases Amfizem Cause of Death in 5-6% 5-7. decades Overinlation is NOT emphysema! More severe in male patients Pathogenesis: Emphysema Imbalance protease(elastase)-antiprotease mechanism Due to action of enzymes (proteases) Source of proteases is leukocytes associated with pulmonary infection Normally, antiproteolytic substances such as antitrypsins in plasma inactivate these enzymes, so protect tissue from damage Excess of proteolytic enzymes ( Neutrophilic infiltration) Or too little antiproteolytic activity (Alfa 1 antitrypsin deficiency) Cigarette smoking- chr. irritation-Neutrophil increasing α1-AT deficiency*** genetic problem Large apical blebs or bullae, obscure the heart, Slowing of forced expiration Voluminous lungs Neutrophils are principal source of cellular elastase Any stimulus that increases the number of PML and Mac Or relase of their elastase containing granules ✓Imbalance at Protease-antiprotease ✓ Imbalance at Oxidants-antioxidants  Emphysema Pathogenesis: II Protease-antiprotease mechanisms Homozygote twins α1 antitrypsine def. Smokers Macrophages and PML ↑, elastase release ↑ Oxidants at cigarette smoke and PML derived free radicals α1 antitrypsine ↓ ✵Macrophage derived elastases not inhibited by α1 antitrypsine  Amfizem Patogenez III antielastase Alpha1 antitrypsine Deficiency in alpha 1 antitrypsine smoking Elastic elastase damage emphysema ☸ ✵Macrophage derived elastases not inhibited by α1 antitrypsin  Amfizem patogenezi ✓Imbalance at Protease-antiprotease ✓ Imbalance at Oxidant-antioxidant  Pi locus on chromosome Amfizem 14 Pi= Protease inhibitor Normal --- polimorphic or contains MM allel When Pi is ZZ homozygous PiZZ (%0.012 USA) very low levels of protease inhibitor in serum (α1 antitrypsine ↓) These patients symptomatic emphysema Amfizem  Amfizem Swollen lungs like feathered pillow, Increased air content Pale and dry Due to loss of elasticity do not shrink when the thorax cage is open  Centrilobular (centriacinar) Emphysema Upper lobes ***apical segments Dilatation of proximal part of asinus ✔not all asini in one lobulus  Centriacinar Emphysema Chronic smokers With chr. bronchitis Pneumoconioses Upper lobes severe involvement  Centriacinar emphysema Smokers have accumulation of neutrophils and macrophages in their alveoli Smoking stimulates release of elastase from neutrophils Enhances elastase activity in macrophages Not inhibited by alpha 1- antitrypsin Proteolytically digest this antiprotease Oxidantas in cigarette smoke and oxygen free radicals by PML inhibit alpha 1 antitrypsin  Panacinar emphysema Total acinar dilatation Lower lobes α1 antitrypsine deficiency Panacinar ve Centriacinar amfizem Distal (paraseptal) emhysemaamfizem Distal dilatation of asini Proximal normal Upper lobes and subpleural areas Fibrosis and atelectasia at surrounding lung 0.5-2 cm multipl cysts Spontaneous pneumothorax at young populations Paraseptal emphysema Distal (paraseptal) amfizem  Irregular emphysema Most common type in daily practice Usually asymptomatic Next to scar tissue with fibrosis (old Tbc )  Condition related to emphysema Amfizem Tipleri 1-Obstructive overinflation emphysema 2-Compansatory emphysema 3-Senile emphysema 4-Interstitial mediastinal emphysema 5- Bulleous emphysema  Emphysema and chronic bronchitis/bronchiolitis Chronic Obstructive Lung Disease (COPD) 🞴USA 10% patients 🞴 4. cause of major deaths KOAH’ta küçük hava yolları patolojisi