Diseases Of Respiratory System

Diseases of respiratory system Chronic Obstructive Pulmonary Diseases Chronic Bronchitis Emphysema

Acute Bacterial Pneumonias Primary Bronchogenic Carcinoma

Structure of respiratory system • Review – Nose – Pharynx – Larynx – Trachea – Bronchi – Bronchioles – Alveolar ducts – Alveoli

COPD Chronic Obstructive Pulmonary Diseases A group of diseases with objective evidence of persisting and irreversible air flow obstruction. Chronic bronchitis; bronchiectasis; asthma; emphysema

Chronic Bronchiti s

• Definition – A persistent productive cough for at least 3 consecutive months in at least 2 consecutive years. – Main symptoms: • Cough • Sputum • Wheezing

• Etiology – Chronic irritation by inhaled substances • Cigarette smoking, air pollution. – It is common among cigarette smokers and urban dwellers in smog-ridden cities, especially men of more than 40 years old. – These predispose to infection of respiratory epithelia

– Microbiologic infections • Bacteria: Haemophilus influenzae, streptococcus pneumoniae • Viruses: respiratory syncytial virus, adenovirus.

Recall of the histology of bronchus • Epithelium: ciliated columnar epithelial cells with a small number of goblet cells. • Two types of bronchial glands. – One secrets mucus – the other secrets serum

• Pathogenesis Cigarette smoking or other air pollutants →hypersecretion of bronchial mucus glands →mucin-secreting goblet cells ↑ maintaining inflammation fibrosis →narrowing of bronchioles and coexistent emphysema.

Morphology • Grossly – the mucosa is usually hyperemia and swollen – mucus or mucopurulent secretions

• Histologically – Injury and repair of mucosa epithelium • Columnar epithelia: degeneration, necrosis, desquamation, cilia lost. • Squamous metaplasia

–changes of glands (feature) –Mucous glands: hyperplasia and hypertrophy (the larger glands lead to the thickening of bronchial walls and narrowing of bronchial lumina ) –Goblet cells: proliferation. –Serous glands: begin secreting mucus

– Lesion of bronchial wall • Inflammatory infiltrate: mononuclear cells in the absence of infection, admixed neutrophils when microbe infects. • Proliferation of smooth muscle, degeneration, calcification and ossification of cartilage.

Pulmona ry emphyse ma

• Definition – Abnormal permanent enlargement of the airspaces distal to the terminal bronchioles accompanied by destruction of their walls, without obvious fibrosis. • respiratory bronchiole • alveolar duct • alveolus

• Etiology – heavy cigarette smoking – Small airway infection: chronic bronchitis – Air pollution – Pneumoconiosis

• Incidence – common, approximately 50% of middle to late adults

• Pathogenesis – Chronic airflow obstruction: • Obstruction of the small airways (often occurs in chronic bronchitis ) induces increased expiratory effort to overcome the airways resistance, compressing the small airways, which lack cartilaginous support. • Thus residual air in acini increases to induce the enlargement of acini.

recall of lung’s histology acinus----the part of the lung distal to the terminal bronchiole (including respiratory bronchiole, alveolar duct and alveolus ).

lobule----a cluster of 3 to 5 acini

• Type of Emphysema – Alveolar emphysema • Centriacinar emphysema • Periacinar/paraseptal emphysema • Panacinar emphysema

– Interstitial emphysema • Accumulation of air in the interstitial tissues

–Other types •Paracicatrical emphysema: near lung scarring area •Bullous emphysema: with bulla (emphysema space more than 1cm in diameter) •Senile emphysema: increased volume of lung often found in aged •Compensatory emphysema: alveolar dilatation that follows collapse or loss of lung substance

　　　　　　　　　左肺下叶大泡性肺气肿 　　　　　　　在全腺泡型肺气肿基础上，有直径超过 1cm 的大囊泡

bullous emphysema

Centriacinar emphysema • the involvement of the lobule lies in the central or proximal parts of the acini: – respiratory bronchioles are affected, while distal airspaces are spared. – both emphysematous and normal airspaces exist within the same acinus and lobule.

Periacinar/Paraseptal emphysema • Distal alveolar sacs and alveolar ducts are predominately involvement. • The proximal portion of the acinus is normal

Panacinar emphysema • The acini are uniformly enlarged from the respiratory bronchiole to the terminal alveoli.

中央型和全腺泡型

度呼 狭吸 　 窄细 　 支　 　 气　 管腺 呈 囊泡 状中 扩央 张型 ，肺 伴 行气 肺肿 动 脉 管 壁 增 厚 ， 管 腔 极

度呼 　 狭吸 　 窄细 　 支　 气　 管腺 呈泡 囊 状中 扩央 张型 ，肺 伴气 行 肺肿 动 脉 管 壁 增 厚 ， 管 腔 极

panacinar (panlobular) emphysema

　　　　　　　　　　全腺泡型肺气肿 　末梢呼吸道弥漫性扩张，呈小囊状遍布于肺小叶内

Morphology • Grossly – Pale – voluminous (so called barrel-shaped) – emphysematous bullae may be grossly visible in extreme cases

　　　　　　　　　 emphysematous bullae

• Microscopic features – Abnormal enlargement of airspaces. – Thinning and destruction of septal wall, sometimes bullae form. – The number of septal capillaries is diminished because of the compression. Fibrous thickness of intima of pulmonary small arteries – Accompanying bronchiolitis

emphysema: increased residual capacity

• Clinical course: – Dyspnea– the first symptom, much more severe during expiration. – Cough-- mucoid or purulent sputum and wheezing sounds – Weight loss – Pulmonary function reduces – Barrel-chested

Barrel chest Because of increased posteroanterior diameter of chest

Cause of death • Respiratory acidosis and coma • Right-sided heart failure • Massive collapse of lungs secondary to pneumothorax.

pneumonia

Definition • Pneumonia is usually due to infection affecting distal airways,especially alveoli,with the formation of inflammatory exudates.

Classification • Etiological agent – Bacterial – Viral – Fungal – Others: mycoplasma

• Other criteria – Clinical circumstances – Host reaction – Anatomical pattern

Bacterial Pneumonias Definition

Bacterial pneumonia is a generic term that refers to inflammation and consolidation (solidification) of the lung parenchyma evoked by bacteria invasion. •Consolidation — A process of becoming solid and firm because air spaces are filled with exudate.

• classification: – Lobar pneumonia – Lobular pneumonia (Bronchopneumonia)

Lobar pneumonia • Lobar pneumonia is an acute bacterial infection of a large portion of a lobe or an entire lobe.

• Etiology – 90%~95% of lobar pneumonias are caused by pneumococi(Streptococcus pneumoniae). – Klebsiella pneumoniae, staphylococci, streptococci, H. Influenza are occasional cause.

• Incidence: It occurs in typically otherwise healthy adults between 20 and 50 year of age.

Morphology • Four stages: – Congestion – Red hepatization – gray hepatization – Resolution

The stage of congestion • Macroscopically – the affected lobe(s) is(are) heavy, boggy, red.

Red, edematous

The stage of congestion • Histologically – Alveolus walls vascular congestion and dilation – alveoli contain proteinaceous fluid, scattered neutrophils and numerous bacteria

The stage of red hepatization • Macroscopically – the lung lobe is distinctly red, firm and airless with liver-like consistency.

Confluent consolidation of all or the majority of a lobe of the lung

• Red • Solid • Consistency resembling fresh liver

The stage of red hepatization • Histologically – Alveolar wall vascular congestion becomes more evident – the alveolar spaces are packed with red cells, fibrin and neutrophils. – the pleura usually demonstrates a fibrinous or fibrinopurulent exudate (plueritis).

The stage of gray hepatization • Macroscopically – the lung is dry 、 gray 、 firm and liver-like in consistency.

gray hepatization in the lower lobe of the lung

• Dry Pale

Firm

The stage of gray hepatization • Histologically – Alveolus wall vascular congestion diminishes – the fibrinous exudate, neutrophils persist and increase within alveoli – the number of RBC relatively reduces (disintegration) – The pleuritis is most intense.

　　　　　　图注：大叶性肺炎 灰色肝变期，肺泡腔完整，肺泡隔内毛细血管明显扩张充 血。腔内渗出的纤维素网络了大量的中性粒细胞。 　　

　

灰色肝样变期 ( 低倍 )

灰色肝样变期 ( 高倍 )

The stage of resolution • Macroscopically – the lung is edematous (boggy and wet).

• Histologically – Alveolus wall vascular congestion reoccurs – Exudates within the alveoli are enzymatically digested and either reabsorbed or expectorated, leaving the basic architecture intact. – The pleural reaction may similarly resolve or undergo organization, leaving fibrous thickening or permanent adhesions.

Clinical Course • The onset is abrupt, with high fever and an episode of a severe shaking chill • Chest pain • A cough productive of rusty-colored purulent sputum (when?) • Dyspnea, most severe during the second stage of red hepatization.

Complications • Suppurative pleuritis and empyema • Pulmonary carnification: organization of the exudate • Bacteremic dissemination: may cause septicemia, pyemia or infective shock • Lung abscess

Pulmonary carnification

Lobular pneumonia • Lobular pneumonia has a characteristic patchy distribution, centered on inflamed bronchioles and bronchi with subsequent spread to surrounding alveoli. Because lobule is made of bronchiole and surrounding alveoli, we also call lobular pneumonia bronchopneumonia.

Etiology • The common agents are staphylococci, streptococci, pneumococci, Haemophillus influenza, Pseudomonas aeruginosa, etc.

Incidence • These people are vulnerable because of lower defensive mechanism. – Infants • With whooping cough, measles.

– The old age • With influenza, chronic bronchitis, etc.

– People suffering from chronic debilitating illness or immunosuppression

Morphology • Macroscopically – foci of inflammatory consolidation are distributed in patches throughout one or several lobes, most frequently bilateral and basal. – The lesions are gray-red to yellow, varying in size up to 0.5 to 1 cm in diameter, poorly delimited in margin. – in severe cases, they may confluent. – The surrounding areas of consolidation is usually hyperemia and edematous, but the large intervening areas are generally normal.

Bronchopneumonia

Morphology • Histologically – focal suppurative exudate fills the bronchi 、 bronchioles and adjacent alveolar spaces. – The centers of suppurative lesions lie in bronchi and bronchioles.

Clinical course • The onset is insidious, often overshadowed by the predisposing condition. • Low-grade fever • Cough with purulent sputum • Course is irregular, lying on the treatment and patient’s condition. • Most can be cured.

Complications • • • •

Respiratory failure Heart failure Pyemia Abscess

小叶性肺炎并发肺脓肿

Primary Lung Tumor

• Primary lung tumor— the tumor arises from the lung tissue – 95% from the bronchial epithelium – bronchogenic carcinomas – 5% are miscellaneous

Bronchogenic Carcinoma

• Incidence: – The number one cause of cancer-related deaths – about 1/3 of cancer deaths in men – the leading cause of cancer deaths in women – The peak incidence of lung cancer occurs between ages 40 and 70 years.

• Etiology and Pathogenesis: – Cigarette smoking – air pollution – Genetic changes

Classification • Macroscopic Classification – Central pattern • the cancers tend to arise centrally in major bronchi.

– Peripheral pattern • the cancers are usually peripherally located.

– Diffuse pattern • the cancers are multiple diffuse nodules that may coalesce to produce pneumonia-like consolidation.

Central pattern

Peripheral pattern

Diffuse pattern

•

Histologic Classification – Non-Small Cell Carcinoma (NSCLC) • • •

Squamous cell carcinoma Adenocarcinoma Large cell undiffereniated carcinoma

– Small Cell Lung Carcinoma (SCLC) – Combined Patterns

• Several common features: – The majority arise in the lining epithelium of major bronchi, usually close to the hilus of the lung. – All patterns are associated with cigarette smoking; the strongest association is with squamous cell and small cell carcinoma. – All patterns are aggressive

Squamous cell carcinoma • Incidence: – the most common histologic pattern • 30-50% of all lung cancers • 80-85% of the central pattern

– more common in men than in women

Squamous cell carcinoma • lMorphology: – Macroscopically : • well-defined tumor mass central in major bronchi

– Histologically

hyperplasia→ squamous mateplasia→ atypical hyperplasia of squamous cells→ carcinoma in situ→ squamous cell carcinoma

Squamous cell carcinoma – Histologically • squamous cell carcinoma – Well-differentiated squamous cell carcinomas show keratin pearls and intercellular bridges. – Poorly-differentiated squamous cell carcinomas have only minimal residual squamous cell features.

• Metastasis: – squamous cell carcinoma are prone to metastasize by lymph – local hilar lymph nodes are usually affected

Small cell lung carcinomas(SCLC) • Incidence: – relatively common (20-25%), and also more common in men than in women.

• Morphology: – Macroscopically • pale, gray, centrally located masses with extension into the lung parenchyma and early involvement of the hilar and mediastinal lymph nodes.

Small cell lung carcinomas(SCLC) • Histologically: – “oat cell” • small 、 dark 、 round-to-oval 、 spindle-shaped or lymphocyte-like cancer cells • with scant cytoplasm • with hyperchromatic nuclei • mitoses are numerous

SCLC

• Metastasis: – They tend to early metastasize by blood stream – SCLCs have invariably spread by the time they are first detected, even if the primary tumor appears small and localized. – They are very sensitive to chemotherapy but invariably recur.

Traits of SCLC • SCLCs are rapidly growing lesions that tend to infiltrate widely and metastasize early in their course and so are rarely resectable.

• They are derived from neuroendocrine cells of the lung, which are characterized by secreting a host of polypeptide hormones including ACTH, calcitonin, gastrin-releasing peptide, and so on. Hence, these tumors are associated with a variety of paraneoplastic syndromes.

Clinical course • often silent and insidious lesions that have spread so as to be unresectable before they produce obvious symptoms. • Chronic cough and expectoration may be the common symptoms in the early stage.

Clinical course • Vena Caval Syndrome: – Clinical signs: • Puffiness of the head and neck; • Varicosity of cervical and thoracic veins.

– Reasons: • The tumors (usually in the upper lobes) compress or infiltrate the superior vena cava to cause venous congestion.

• Horner’s Syndrome: – Clinical signs: • • • •

Ipsilateral enophthalmos Ipsilateral Ptosis Miosis Anhidrosis of thoracic skin

– Reasons: • The apical neoplasms (sometimes so called Pancoast’s tumors) compress or invade the cervical sympathetic plexus.

• other symptoms: – The severe pain or atrophy of the muscles in the distribution of the ulnar nerve.

• Reason: – The apical neoplasms compress or invade the brachial plexus.

Paraneoplastic Syndrome(usually in SCLCs) • Signs:

• Reasons:

Hypercalcemia --------------------------------- Secretion of a parathyroid hormone-related peptide (often with squamous cell carcinomas) Hematologic manifestations (often with adenocarcinomas) including migratory thrombophlebitis, nonbacterial endocarditis and DIC Cushing’s syndrome--------------------------- increased production of ACTH SIADH (hypertension, puffiness)----------- inappropriate secretion of antidiuretin (ADH) Neuromuscular syndrome including myasthenic syndrome, neuropathy, polymyositis Clubbing of the fingers Hypertrophic pulmonary osteoarthropathy

• Symptoms emanating from metastases – Mental or neurologic changes – Hepatomegaly – Bones pain

Attention: when hoarseness 、 chest pain 、 superior vena caval syndrome 、 pericardial or pleural effusion 、 or persistent segmental atelectasis makes its appearance, the prognosis is grim.