RESPIRATORY SYSTEM

Department of Anatomic PathologyFaculty of MedicineBrawijaya University

• Tingkat Kemampuan 2• Lulusan dokter mampu membuat diagnosis

klinik terhadap penyakit tersebut dan menentukan rujukan bagi pasien kepada spesialis yang relevan. Lulusan dokter juga harus mampu menindaklanjuti sesudahnya.

• Tingkat Kemampuan 3• 3A. Lulusan dokter mampu memberikan

penanganan terhadap penyakit tersebut pada keadaan yang bukan keadaan gawat darurat serta mampu memberikan terapi pendahuluan demi menyelamatkan nyawa atau mencegah keparahan dan atau kecacatan pada pasien. Lulusan dokter harus dapat menentukan rujukan yang paling tepat bagi penanganan lebih lanjut untuk pasien dan mampu menangani perawatan selanjutnya.

• 3B. Lulusan dokter mampu memberikan penanganan gawat darurat pada penyakit tersebut dan mampu memberikan terpai pendahuluan demi menyelamatkan nyawa atau mencegah keparahan dan atau kecacatan pada pasien. Lulusan dokter harus dapat menentukan rujukan yang paling tepat bagi penanganan lebih lanjut untuk pasien dan mampu menangani perawatan selanjutnya.

•  • Tingkat Kemampuan 4• Lulusan dokter mampu menangani penyakit

tersebut secara mandiri dan tuntas. Mereka harus mampu menegakkan diagnosis pasien berdasarkan pemeriksaan fisik dan pemeriksaan penunjang (misalnya: pemeriksaan laboratorium sederhana atau X-ray) yang tepat guna dan tidak berlebihan.

KOMPETENSI

Diagnosis RujukDiagnosis 1st Treatment (Non

Emergency) rujukDiagnosis 1st treatment (Emergency)

RujukDiagnosis Appropriate Treatment

1 Cystic fibrosis 2 14 PleuritisTB 3A

2 Bronchopulmonary dysplasia

3A 15 Pleural Effusion

3 Uncomplicated Pulmonary Tuberculosis

4 16 Pneumothorax 3B

4 TB with HIV 4 17 Aspiration pneumonia

3A

5 TB with pneumothorax 2 18 Pleuritis Cancer 2

6 Multi Drug Resistance TB

19` Pleuritis Lupus 2

7 Acute Bronchitis 4 20 Bronchial asthma

4

8 Bronchiolitis 3A 21 Status asmaticus 3B

9 Bronchiectasis 3A 22 Lung emphysema

3A

10 SARS 3B 23 Atelectasis 3B11 Pneumonia 3B 24 COPD 3A12 Bronchopneumonia 25 Pertussis 413 Avian influenzae (THT) 3B

DISEASES of RESPIRATORY SYSTEM

• ATELECTASIS• COPD

(EMPHYSEMA)• PULMONARY

TUBERCULOSIS• LUNG CANCER

• Definition• Pathophysiology

– Macros– Micros – X-Ray

• Clinical Appearance• Management

ATELECTASIS

What is it?# Atelectasis (at-uh-LEK-tuh-sis) is a condition in

which one or more areas of lungs collapse or don't inflate properly.

# Incomplete expansion of the lung (neonatal atelectasis) or collapse of previously inflated lung (acquired atelectasis), producing areas of relatively airless pulmonary parenchyma

# Reversible

Possible Underlying Disease

• Lung diseases such as COPD, asthma, cystic fibrosis, tuberculosis, and whooping cough also increase your risk for a collapsed lung

Cause of Atelectase• Acquired atelectasis

– resorption ( obstruction) atelectasis – compression atelectasis– contraction atelectasis

Resorption atelectasis * Complete obstruction of an airway resorption of the oxygen trapped in the dependent alveoli lung volume diminished mediastinum shifts toward the atelectatic lung * Cause : excessive secretions (e.g., mucus plugs) or exudates within smaller bronchi most often found in bronchial asthma, chronic bronchitis, bronchiectasis, postoperative states, aspiration of foreign bodies, bronchial neoplasms (rarely)

Compression atelectasis * Cause : the pleural cavity is partially or completely filled by fluid exudate, tumor, blood, or air (pneumothorax) mediastinum shifts away from the affected lung Contraction atelectasis * Cause : local or generalized fibrotic changes in the lung or pleura prevent full expansion

Contraction

Resorption

Compression

Clinical Feature• cough, but not prominent• chest pain• breathing difficulty• low oxygen saturation• pleural effusion (transudate type)• cyanosis (late sign)• increased heart rate

Management• Based on the predetermined cause

– Non Pharmacological non Invasive• chest physiotherapy : including postural

drainage, chest wall percussion and vibration, and a forced expiration technique (called huffing)

– Non Pharmacological invasive• Suctioning• Bronchoscopy

– Pharmacological• Antibiotic if there is evident of infection• Nebulized bronchodilators and humidity

may help liquefy secretions and promote their easy removal

Learning Resources• http://emedicine.medscape.com/artic

le/296468-overview

COPD

COPD (chronic obstructive pulmonary disease ) * Emphysema (acinar level) * Chronic bronchitis (bronchial level) - Commonly caused by cigarette smoking - The fourth leading cause of morbidity and mortality in USA

Emphysema :• Condition of the lung

characterized by irreversible enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls without obvious fibrosis

Types of Emphysema (according to its anatomic distribution within the lobule) Four major types : (1) Centriacinar (centrilobular) (2) Panacinar (panlobular) (3) Paraseptal (distal acinar) (4) Irregular

* Centriacinar and panacinar cause clinically significant airflow obstruction * Centriacinar emphysema : > 95% of cases

Centriacinar EmphysemaThe central or proximal parts of the acini, formed by respiratory bronchioles, are affected, whereas distal alveoli are spared - > severe in upper lobes, particularly apical segments - Walls of the emphysematous spaces : black pigment (++) - Inflammation around bronchi and bronchioles (+) - Severe distal acinus may also be involved differentiation from panacinar emphysema : difficult - >> in heavy smokers, often in association with chronic bronchitis

Panacinar Emphysema The acini are uniformly enlarged from the level of the respiratory bronchiole to the terminal blind alveoli - The prefix "pan" refers to the entire acinus but not to the entire lung - Tends to occur more commonly in the lower zones and in the anterior margins of the lung, and usually most severe at the bases. - Associated with α1-antitrypsin (α1-AT) deficiency

Paraseptal EmphysemaThe proximal portion of the acinus is normal, and the distal part is predominantly involved - More striking adjacent to the pleura, along the lobular connective tissue septa, and at the margins of the lobules - Occurs adjacent to areas of fibrosis, scarring, or atelectasis and is usually more severe in the upper half of the lungs - Multiple, continuous, enlarged airspaces from < 0.5 cm to > 2.0 cm in diameter, sometimes forming cystlike structures

Irregular Emphysema (Airspace Enlargement with Fibrosis)The acinus is irregularly involved, almost invariably associated with scarring - In most instances, are asymptomatic and clinically insignificant

Other forms of emphysemaCompensatory Hyperinflation /Emphysema - Dilation of alveoli but not destruction of septal walls in response to loss of lung substance elsewhereObstructive Overinflation - Caused by subtotal obstruction by a tumor or foreign object

Bullous Emphysema - Large subpleural blebs or bullae ( Ø >1 cm ) - Occur in any form of emphysema - Occur near the apex, sometimes in relation to old tuberculous scarring. - Sometimes : rupture pneumothorax

Interstitial Emphysema * Entrance of air into connective tissue stroma of the lung, mediastinum, or subcutaneous tissue * Caused by : - alveolar tears in pulmonary emphysema - fractured rib that punctures the lung

Possible Cause/Risk Factor

• Smoking• Prolonged infection

Pathogenesis# The protease-antiprotease imbalance hypothesis - Genetic deficiency of the antiprotease α1- antitrypsin (normally present in serum, tissue fluids, and macrophages, a major inhibitor of proteases particularly elastase) - Activated neutrophils (in smokers) ROS inactivation of α1-antitrypsin elastase activity ↑ tissue damage pulmonary emphysema

# Smoking* Neutrophils and macrophages accumulate in alveoli - Chemoattractant effects of nicotine - Effects of ROS (free radicals) contained in smoke activated neutrophils /macrophages proteases (elastase, etc) release tissue damage * Oxidant-antioxidant imbalance - Tobacco smoke : ROS/free radicals (++) deplete antioxidant mechanisms tissue damage * Activated neutrophils ROS inactivation of α1-antitrypsin

Clinical course :Appear if > ⅓ of pulmonary parenchyma is damaged - Dyspnea - Cough - Wheezing confused with asthma - Weight loss - Barrel-chest - Expiratory airflow limitation best measured through spirometry (the key to diagnosis)

PULMONARY TB

PULMONARY TUBERCULOSIS

• Caused by : Mycobacterium Tuberculosis

• Tissue reaction : - Granulomatous reaction (tubercle): - Hard tubercle - Soft tubercle

• Mode of transmission : 1. airborne dropled

2. food 3. skin 4. feces

• Primary TBC* Develops in a previously unexposed,

and therefore unsensitized person* Usually occur in children & infant* Sometimes occur in previously unexposed

or profoundly immunosuppressed adults

Pathogenesis : * Bacilli lower part of the upper lobe/upper part of the lower lobe (close to the pleura) sensitization Ghon focus (1- 1.5 cm area of gray white inflammatory consolidation, caseous necrosis +) regional nodes +, >>caseate (+) Ghon complex (GF+ regional nodes)

* In the first few weeks lymphatic/ hematogenous spread may occur. * ± 95% of cases cell-mediated immunity Ghon complex fibrosis calcification

Secondary TBC * Arises in a previously sensitized host - Reactivation of dormant primary lesions (more common in low-prevalence areas) - Reinfection (in regions of high contagion)

* Localization : - Apex of the upper lobes of one / both lungs walling off regional lmn << cavitation dissemination along the airways / erosion into an airway dropled infection

MACROS : The initial lesion : - Ø<2 cm, 1-2 cm of the apical pleura. - Sharply circumscribed, firm, gray-white to yellow - Central caseation, peripheral fibrosis - Fibrous encapsulation fibrocalcific scars

MICROS : -Coalescent tubercles with central caseation -Heal with fibrosis : spontaneously / tx (+) -Progress and extend along several different pathways

Pulmonary TB

Hard Tubercle

Soft Tubercle

Questions ?

LUNG CANCER

FACT• The U.S. Environmental Protection Agency

(EPA) has published a major assessment of the respiratory health risks of passive smoking ( Respiratory Health Effects of Passive Smoking: Lung Cancer and Other Disorders  EPA/600/6-90/006F). The report concludes that exposure to environmental tobacco smoke (ETS) -- commonly known as secondhand smoke -- is responsible for approximately 3,000 lung cancer deaths each year in nonsmoking adults and impairs the respiratory health of hundreds of thousands of children.

LUNG CANCER * The most common cause of cancer mortality worldwide * Largely due to the carcinogenic effects of cigarette smoke * In the United States 2008 : - New cases ± 215.020 (1950 : 18.000) - Number of deaths ± 161.840 * Occurs most often between ages 40 - 70 years (peak incidence in the 50s or 60s)

Etiology and PathogenesisTobacco Smoking Statistical evidence : * 87% of lung ca occur in active smokers * There was an invariable statistical association between the frequency of lung cancer and : (1) the amount of daily smoking (2) the tendency to inhale, and (3) the duration of the smoking habit * Risk : - Average smokers of cigarettes 10× > Ca - Heavy smokers (>40 cgrts / day for several years) 60× > Ca - Women : susceptibility to tobacco > men

Clinical evidence * Histologic changes in the lining epithelium of the respiratory tract in habitual smokers : squamous metaplasia squamous dysplasia ca in situ invasive ca * Lung tumors of smokers frequently contain mutations in the p53 gene (probably caused by benzo[a]pyrene, one of carcinogens in tobacco smoke)

Experimental work * >1200 substances in cigarette smoke, carcinogens (++) - Initiators (PAH : benzo[a]pyrene, etc) - Promoters : phenol derivatives, etc - Radioactive elements : polonium-210, carbon-14, and potassium-40 - Other contaminants : arsenic, nickel, molds, and additives

Industrial hazzards * High-dose ionizing radiation : carcinogenic Survivors of the Hiroshima and Nagasaki atomic bomb blasts : incidence of lung ca ↑ * Uranium : - Nonsmoking uranium miners : 4× > population - Smoking miners : 10× > population * Asbestos : - Nonsmoking asbestos workers : 5× > - Smoking asbestos workers : 50 to 90× > - Latent period : 10 to 30 years

Air pollutiont * Radon : radioactive gas Lung CaGenetics Histologic types of lung cancer :Can be clustered into two groups on the basis of likelihood of metastases and response to available therapies: small cell carcinoma (almost always metastatic, high initial response to chemotherapy) versus non-small cell carcinoma (less often metastatic, less responsive).

Histologic Classification of Malignant Epithelial Lung Tumors Squamous cell carcinoma Small-cell carcinoma Combined small-cell carcinoma Adenocarcinoma Acinar; papillary, bronchioloalveolar, solid, mixed subtypes Large-cell carcinoma   Large-cell neuroendocrine carcinoma Adenosquamous carcinomaCarcinoma with pleomorphic, sarcomatoid, or sarcomatous elementsCarcinoid tumor Typical, atypicalCarcinoma of salivary gland type Unclassified carcinoma

The four major categories : * Adeno ca (males 37%, females 47%) * Squamous cell ca (males 32%, females 25%) * Small cell ca (males 14%, females 18%) * Large cell ca (males 18%, females 10%)

Morphology * Arise most often in and about the hilus * ± ¾ : origin from first-order, second-order, and third-order bronchi. * Arise in the periphery (from the alveolar septal cells or terminal bronchioles : predominantly adeno ca, including bronchioloalveolar type

Adenocarcinoma * Acinar, papillary, bronchioloalveolar, and solid with mucin formation * The most common type of lung cancer in women and nonsmokers * Peripherally located, tend to be smaller * Grow > slowly than squamous cell ca, but tend to metastasize widely and earlier * Less frequent associated with history of smoking (75% are found in smokers, while squamous or small cell ca ≥98% in smokers)

Squamous Cell Carcinoma * Most common found in men and closely correlated with a smoking history * Arise most common centrally from the segmental or subsegmental bronchi * Well - moderately - poorly diff * Squamous metaplasia, epithelial dysplasia, and ca in situ may be seen in bronchial epithelium adjacent to the tumor mass

Small Cell Carcinoma * Highly malignant, most aggressive, metastasize widely, incurable by surgical * The cells are relatively small, round, oval, or spindle-shaped, with scant cytoplasm, ill-defined cell borders, finely granular nuclear chromatin (salt and pepper pattern), absent or inconspicuous nucleoli, nuclear molding prominent, mitotis (++) * Grow in clusters, glandular/squamous organization (-) * Necrosis (++) * Have a strong relationship to cigarette smoking, only ± 1% occur in nonsmokers * May arise in major bronchi or in the periphery of the lung

Large Cell Carcinoma * Undifferentiated malignant epithelial tumor * Large nuclei, prominent nucleoli, moderate amount of cytoplasm * Probably represent squamous cell ca/adeno ca that are so undifferentiated

The major presenting complaints :

* Cough (75%), Weight loss (40%),

* Chest pain (40%), Dyspnea (20%)

Prognosis :Adeno ca and squamous cell ca tend to

remain localized longer better prognosis than undiff ca

(usually advanced while discovered)

Diagnosis :Clinical Dx : Ax, Physical exam.

Rö : X Photo, USG, CT ScanPA : Cytology (sputum, bronchial

washing/brushing), FNAB, Histopathology

Summary• We have discussed the most common

(Chosen) pathologic feature of diseases in Pulmonary System

• Smoking play important role in causing the most pathologic abnormality

• Campaign how to prevent is the best way to treat the diseases in Respiratory system

Thank You For

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