Middle Examination Multiple choice 50% Short answers 25% Long answers 10% Case analysis 15% The weekend of 10th week, 150 min 总论+心血管系统疾病

Chapter 9 Diseases of the Respiratory System Department Of Pathology Guangxi Medical University Zili Lv 吕自力 lvzili@yahoo.com.cn

Anatomic Structures and Functions Good afternoon everybody, today we will talk about some diseases happened in respiratory system. Ok, first, please let me introduce myself. My name is lvzili, my english name is lilian, I wish you can enjoy my teaching. And if you have any question, please do not hesitate to put up your hand and ask me, ok? Ok, let’s begin. First we go over the anatomic structures about respiratory system. Do you remember what is the respiratory composed of? The respiratory system is divided into three principal divisions: Conducting portion: nasal cavity, nasopharynx, larynx, trachea, bronchi and bronchioles. Transitional portion: including respiratory bronchioles. Respiratory portion: consists of the alveoli and their associated structures. Histological structure of the trachea: Pseudostratified columnar, ciliated epithelium Goblet cells Sero-mucous glands Cartilage rings Nose, sinuses, nasopharynx, larynx, Trachea, bronchi, bronchiloe, terminal bronchiloe, Warm, filter, humidify the air Speech, air exchange Alveolar pneumocyte Speudostratified clolumnar

Bronchi Bronchioles Alveolar ducts Alveoli

It is chest x-ray picture, the white part is the heart, and the dark is lung, it is clear.

Clinical features of respiratory diseases 1. Cough 2. Sputum Production咳痰 3. Hemoptysis 咯血 4. Dyspnoea呼吸困难 5. Cyanosis紫绀 6. Chest pain cough: the most common symptoms. caused by entrying of foreign material into the larynx; accumultion of secretion in the lower respiratory tract. Two types: dry cough—without any sputum Sputum production: examination of sputum is useful, can find the reason: tumour or infection Hemoptysis: blood in the sputum. Reasons: left heart failure---lung congestion; lung infarction;lung tumor Dyspena: difficult to breath. Obstruction of the tract, pain Cyanosis: the color of the skin and mucous membranes have been changed , Chest pain: means the parietal pleura is involoved

Contents (6 hrs) 1. Pulmonary infections 2. Chronic obstructive pulmonary diseases & chronic cor pulmonale 3. Chronic diffuse interstitial lung disease, carcinoma of nasopharynx and lung.

Pulmonary infections Acute Pneumonia Chronic Pneumonia

Classification of pneumonia Clinical circumstance Primary and Secondary Etiological agent Bacterial, Virus, Fungal Host reaction Fibrinous & Suppurative Anatomical pattern Lobar & Lobular Acute pneumonia is an acute inflammation of the lung parenchyma resulting from infection of alveoli and respiratory bronchioles. When it occur in a healthy individual----primary The patient is seriously ill, the infection is secondary,

Case 1 analysis History: Male, 20, after suffering from cold and drunk, got high fever, chill, rapid breathing and chest pain. After 2 days, he coughed with “rusty” sputum.

T: 40℃, R: 32 times/min. Chest x-ray: show large-area uniform dense well-delimited shadow in his left upper lobe. Blood examination: WBC: 13.5x 109/ L

BACTERIUM PNEUMONIA Lobar pneumonia Lobular pneumonia Legionella pneumonia

Lobar pneumonia Affects a large part, or the entirety of a lobe Relatively uncommon in infancy and old age Affects males more than females 90% due to pneumococcus (肺炎球菌） Cough and fever with purulent or Rusty Sputum铁锈色痰

A. Etiology Pathogen: Streptococcus pneumonia 肺炎球菌 III型 Infective Route: Inhalation, Aspiration 吸入 Risk Factors： Cold, drunk, tired, diabetes Inhalation: the bacterium comes from atmosphere Aspiration: the bacterium stay in the nose sinus

B. Pathology* Acute exudative fibrinous inflammation （急性纤维素性炎） Involves one whole lobe or several lobes The bronchi are not involved

Acute congestion 充血水肿期 Red hepatization 红色肝样变期 Pathologic Features Acute congestion 充血水肿期 Red hepatization 红色肝样变期 Gray hepatization 灰色肝样变期 Resolution 溶解消散期

1. Stage of acute congestion 1st-2nd day (1)Gross changes: Heavy, dark red and firm (2)Microscopic change Fluid, RBC, WBC in the air space (3)Clinical features: Acute congestion is the early stage of infection: the bacteria are replicate in the alveolar space, and spread to the others, the normal alveolar defense have been overcome, the capillaries will be invloved

Stage of acute congestion Active dilation of alveolar capiilaries The normal space is filled with air, but the in the lobar pneumonia, is filled with fluid Alveolar capillaries: Dilated Air space: Fluid, RBC, WBC

Stage of acute congestion Clinical Features Fever, cough, cyanopathy (发绀) Chest pain Bacteremia Bacteria can be found in sputum

（1）Grossly 2. Stage of Red Hepatization: 2nd-4th day Red and consolidation, just like liver （1）Grossly

(2)Microscopic changes of red hepatization A. Capillaries congestion B. Exudation: Fibrin, large number of RBC C. Fibrinous pleurisy

Microscopical changes Alveolar congestion is still present The alveolar space is filled with red blood cells, neutriphils, fibrin

红色肝样变期X线特点 (3) Chest x-ray The middle segment of right upper lobe become consolidated and show large-area uniform dense shadow. 红色肝样变期X线特点

(4) Clinical features of red hepatization Fever, cough, chest pain Rapid breathing, cyanopathy Dullness浊音 Vocal fremitus enhancement 语颤增强 Rusty sputum 铁锈色痰 The infection is controlled at this stage, either naturally or by antibiotic therapy, which eliminate the bacterium Rusty sputum: the RBC is phagocytosed by macrophage, the RBC will be dissoved---hemosiderin laden macrophages

3. Stage of gray hepatization: 5th-6th day (1)Gross changes of grey hepatization Dry Gray Firm Consolidation

(2)Histological changes Capillary is not dilated anymore. Alveolar space is filled with neutrophil and fibrin

Histological changes of grey hepatization The features of consolidation are still present. But the infection has been controlled and there is neither hyperemia nor continued exudation and neutrophil emigration The fibrinous exudates persist within the alveoli.

X-ray features of gray hepatization (3)Chest x-ray: high dense shadow can be found at the right upper lobe X-ray features of gray hepatization

(4)Clinical features of gray hepatization Consolidation: dullness, vocal fremitus enhancement Sputum: mucus purulent sputum Dyspnoea(缺氧）: is not obvious

4. Stage of Resolution, 7 days later Gross changes: Friable and mottled Microscope: The fibrin and cell debris are digested by enzymatic, The exudation is remove.

Chest X-ray

Pathologic Features (4 stages) Acute congestion Red hepatization Grey hepatization Resolution

LOBULAR PNEMONIA 小叶性肺炎 (Bronchopneumonia) (支气管肺炎)

The lobule includes 3-5 terminal bronchioles and their distant structure. Includes: respiratory bronchioles,alveolar duct, alveolar sacs and alveolus

Lobular pneumonia Bronchopneumonia Bronchi are infected Patchy consolidation Centred on inflamed bronchioles or bronchi Secondary pneumonia Less virulent agents, in infancy or old age Suppurative inflammation化脓性炎

A. Etiology Pathogen: many bacteria, Infection via: Inhalation, Aspiration Risk Factors: Secondary In patients who develop secondary pneumonias of a bronchopneumonia pattern---many bacteria,such as staphylococcus aureus, gram-negative bacilli

B. Pathology Gross: Lower lobes, dorsal side Multiple firm areas, around inflamed bronchioles. Lobular pneumonia is characterized by foci of acute suppurative inflammation centered on bronchioles. The consolidation may be patchy through one lobe but is more frequently multilobar and frequently bilateral and basal The lesions are gray-red to yellow, and up to 0.5 to 1 cm in diameter. Confluence of these foci producing confluent bronchopneumonia.

Dry, granular, gray-red to yellow, and poorly delimited at the their margins They vary in size up to 0.5 to 1 cm in diameter. Confluences of these foci occurs in the more florid instances

Microscope: 1. Multiple lesions Purulent bronchitis and bronchiolitis (化脓性细支气管炎) 2. Alveolar spaces surrounding the lesions are filled with neutrophil 3. Compensatory emphysema (代偿性肺气肿)

Suppurative exudate fills the brochi and adjacent alveolar spaces Neutrophils are dominat in this exdation.

C. Clinical Features The onset is insidious, nonspecific Low-grade fever Dyspnea is not prominent The typical feature is Purulent Sputum脓痰*

Chest x-ray Several scattered patchy shadows evidently in bilateral lower lobes

Legionella pneumonia, 军团菌肺炎 嗜肺军团杆菌 急性纤维素性化脓性炎—典型病例,严重者坏死—脓肿 临床表现复杂:肺内\外表现  

Legionella pneumonia, 军团菌肺炎                                                        急性纤维素性化脓性炎 acute fibrino-purulent exudative pneumonia

军团菌病(legionaires disease)是由革兰染色阴性的嗜肺军团杆菌(legionella pneumophila)引起的一种以肺炎为主的全身性疾病，1976年被确认。

Resolution Lobar pneumonia Air space pneumonia Lobular pneumonia Complications

Complications of acute air space pneumonia Pleura involvement Bacteremia Suppuration (Abscess Formation) Necrotizing bacterial pneumonia Pulmonay carnification肺肉质变 Pleura involvement: the pleura is involved, the inflammation spread to the pleura Bacteremia: is the most serious complication of pneumococcal penumonia.---death, meningitis and endocarditis Suppuration: liquefactive necrosis of alveoli leading to areas of destryoed lung replaced by pus Necrotizing bacterial pneumonia: rare complication, extremly severe necrosis of the lung associated with rapidly progressive disease with a high mortality rate. Pulmonary carnification: the exudation is taken place by granulation tissue It may convert part of lungs into solid tissue.

Lung abscess

Pulmonary carnification

What are the differences? Distribution Number Host reaction Clinical Features

Acute interstitial pneumonia间质性肺炎 1. Agents: Virus (SARS, Avian influenza, Swine Flu) and Mycoplasma or Pneumocystis 2. Interstitium 3. Atypical pneumonia 4. Infiltration with lymphocyte, monocyte Acute interstitial pneumonia results from infection by agents that are predominantly obligate intracellular pathogens. Infection with these pathogens evokes an acute inflammation that is usually restricted to the interstitum wihtout involvement of the alveolar spaces.

Pathologic Features of Viral pneumonia The alveolar septa are expanded Cell infiltrate: lymphocyte, plasma cells Air spaces are air filled Epithelial necrosis Inclusion bodies 病毒包涵体 Multinucleated giant cells 多核巨细胞 Hyaline membranes 透明膜 The septa is expanded by hyperemia, edema, and a cellular infiltrate composed of lymphocytes and plasma cells Inclusion bodies: cytomegalovirus

Viral Pneumonia Hayline membrane Expanded septum Necrosis of epithelial Inclusion bodies

SARS Severe Acute Respiratory Syndrom (SARS) 重症急性呼吸综合征 Atypical pneumonia（非典型肺炎） Cornonavirus 变异的冠状病毒 Extensive consolidation, hyaline membrane, necrosis, pulmonary fibrosis Die in respiratory distress Cornonavirus, a new member of the family coronviridae

In the end of 2002 to 2003, SARS came to be epidemic all over the world, especially in Asia, in China, over 5000 people suffered from this disease, more than 50% died in this disease. many people had to wear the respirator , kitten too, the murderer was the virus, coronarovirus.

Clinical features Fever, usually greater than 38, chills, cough ,dyspnea, difficult in breath, headache, diarrhea, Flu-like

Hyaline membrane Necrosis of epithilum Diffuse alveolar damage in varying phases of organization Multinucleated giant cells

Electro microscope Under electro microscope, we can see in the plasma of the cell, replication of the virus

Avian Influenza 禽流感 H5N1 Interstitial Atypical 人畜共患传染病 Avian influenza is called as bird flu Infectious disease of birds caused by strains of the influenza virus 人畜共患传染病

Bird flu An infection disease of birds 1997, Hong Kong, outbreak Vascular disturbances Fever, cough All the other organs can be affected, for example, liver, heart and kidney. This is a bird disease caused by infection of strains of the influenza virus, The first cases of avian influenza viruses in humans happened in 1997, Hong Kong, it killed more than 140 million birds and 60 people.

H1N1, Swine influenza A

H1N1, Swine influenza A 临床表现 轻症：同普通流感；重症：肺炎，坏死性脑病 合并症：急性呼吸窘迫综合征 病理：肺部表现为支气管壁坏死、中性粒细胞浸润、弥漫性肺泡损害伴肺透明膜病变。 发病机制：病毒损伤肺泡微血管导致肺出血与血栓形成，体内免疫因子可对抗病毒感染并修复损伤，但炎症反应过度、渗出液充满肺组织又使肺瘢痕形成，进而限制肺功能。

H1N1 and H5N1

Mycoplasma pneumonia 支原体肺炎 Interstitial pneumonia Atypical pneumonia Congested, edematous, mononuclear cells infiltration The patient is an adolescent or a young adult Respiratory symptoms may be minimal or severe, Pathcy ,segmental in distribution

Lobar pneumonia Air space pneumonia Lobular pneumonia Viral pneumonia Interstitial pneumonia Mycoplasma pneumonia

ARDS Acute Respiratory Distress Syndrome An acute diffuse alveolar injury Terminal events in many of the patients Serious ill, the mortality rate > 50% Results from ischemic, endotoxins, enzymes.

Case 1 analysis History: Male, 20, after suffering from cold and drunk, got high fever, chill, rapid breathing and chest pain. After 2 days, he coughed with “rusty” sputum.

T: 40℃, R: 32 times/min. Chest x-ray: show large-area uniform dense well-delimited shadow in his left upper lobe. Blood examination: WBC: 13.5x 109/ L

Questions What is the diagnosis? Which type of inflammation? Why does the patient cough with the “rusty” sputum?

WHY? Half a year later, this student was enrolled to the army. The chest x-ray indicated there was a nodule in his left lung. The nodule was checked under microscope, there was much granulation tissue in the alveolar spaces. WHY?

Case abstract 2 Male, 70-year-old, he had suffered hypertensive heart disease and left heart failure for half a year, and cough and expectoration for 1 year. These symptoms aggravated 4 days ago with fever and purulent sputum.

T: 38℃, HR: 112 times/min, R: 35 times/min, BP: 22.6/13.5 kPa. Blood WBC: 10.2 X 109/L X-ray: Several scattered patchy shadows evidently in bilateral lower lobes.

Questions What is the diagnosis? Which type of inflammation? Why do patients cough with the purulent sputum?

Summary How to differentiate the lobar pneumonia and the bronchopneumonia? What is the “rusty sputum”?

See you next time! 2017/4/16 79