Respiratory Diseases

Transcription

1 8-year system Curriculum 6nd Week Theme Respiratory Diseases ZHANG WEI ( 张伟 ) Associate Professor, Ph.D. Institute of Pathology & Forensic Medicine Department of Pathology & Patho-physiology Zhejiang University School of Medicine zwei72@zju.edu.cn

2 Diseases Chronic obstructive pulmonary disease, COPD Chronic bronchitis Pulmonary emphysema Bronchiectasis Bronchial asthma Pneumoconiosis:Silicosis Chronic cor pulmonale Pulmonary infections: Pneumonia Lobar pneumonia Lobular pneumonia Interstitial pneumonia Pulmonary tuberculosis Tumors of lung

3 Pneumonia Broadly defined:any infection in the lung. Pathologically Defined: any inflammation of lung due to infection affecting distal airways, especially alveoli, with the formation of an inflammatory exudate.

4 Classification of pneumonia 1. Etiological classification: bacterial pneumonia viral pneumonia fungal pneumonia mycoplasma pneumonia etc.

5 2. Anatomical classification: lobar pneumonia lobular pneumonia interstitial pneumonia

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7 The anatomical classification may give a great help to the etiological diagnosis some times. > 90% lobar pneumonia: caused by Streptococcus pneumoniae (pneumococcus) ; interstitial pneumonia are caused by virus or mycoplasm.

8 Bacterial Pneumonia Lobar pneumonia Def. an acute bacterial infection resulting in fibrinosuppurative consolidation of a large portion of a lobe or of an entire lobe. often seen in previously healthy young adults. Symptoms: abrupt onset, high fever, shaking chills, pleuritic chest pain, a productive mucopurulent cough ( rusty sputum )

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11 Etiology pathogens: streptococcus-pneumoniae, pneumobacillus inducing factors: cold, excessive tired, anethesia Pathogenesis bacteria---alveoli---proliferate, capillary dilate, serious exudates---kohn s pores---spreading entire lobe

12 Morphology For purposes of description, it is convenient to divide the process into four phases: (1) Congestion (1st-2nd day) (2) Red hepatization (consolidation) (3rd-4th day) (3) Gray hepatization (5th-6th day) (4) Resolution (1 week)

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14 1. Congestion stage (1st-2nd days) the outpouring of a protein-rich exudate into alveolar spaces and rapid proliferation of bacteria. grossly: LM: heavy, red, boggy A frothy blood-stained fluid can be squeezed from the cut surface. alveolar wall: cap. dilate, congestion alveolar space: proteinaceous edema fluid, few neutrophils, RBC, and numerous bacteria. Clinically: the onset is sudden with fever and rigors.

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16 2. Red hepatization stage (3rd-4th day) grossly: the lobe distinctly red, firm, and airless with a liver-like consistency LM: Septal capillaries are congested markedly Alveolar spaces are packed with many red cells, and several neutrophils, fibrin the pleura usually demonstrates a fibrinous or fibrinopurulent exudates.

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19 3. Gray hepatization stage (5th 6th day) grossly: gray-brown and more solid, liver like consistency Pleural surface is covered with a confluent fibrinous exudates. The cut surface is dry and granular but of a grayish-white color. LM: Congestion of septal capillaries lightens. The fibrinous exudate persists within the alveoli and a fibrin net forms. There are many neutrophils but is relatively depleted of red cells in the alveoli.

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23 4. Resolution stage (7th-9th day) the resorption of exudate and enzymatic digestion of inflammatory debris, with preservation of the underlying alveolar wall architecture Gross: softening, volume LM: WBC fibrin absorbed

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25 Complication 1. pulmonary carnification: hypoexudation of neutrophils---proteinase defficiency/ over-exudation of fibrin---organization of the intra-alveolar exudate convert areas of the lung into solid fibrous tissue. 2. Tissue destruction and necrosis may lead to abscess formation. 3. Suppurative material may accumulate in the pleural cavity, producing purulent pleurisy and empyema. 4. Septicemia or pyemia: Bacteremic dissemination may lead to meningitis, arthritis, or infective endocarditis. 5. Infective shock: Failure of terminal circulation and appearance of toxic symptoms.

26 Pulmonary carnification

27 Lobar pneumonia(carnification)

28 Lobular pneumonia (Bronchopneumonia) Conception: Defined as an acute purulent inflammation characterized by diffuse patchy pneumonic consolidation often with bronchiolitis in its center. clinic: infants, the aged, and those suffering from chronic debilitating illness or immunosuppression. children: Whooping cough and measles are important antecedents adult: influenza, chronic bronchitis, alcoholism, malnutrition, and carcinomatosis are all predisposing conditions. patchy distribution, a purulent inflammation that centered bronchioles.

29 Etiology and pathogenesis Pathogens: staphylococci, pneumococci, streptococci, influenzae haemophilus Induce factors: cold, heart failure Infection ways: respiratory tract, blood

30 Morphology gross: patchy consolidation through one lobe, more often multilobar and frequently bilateral and basal 0.5-1cm,gray-red to yellow, slightly elevated, poorly delimited at the margins Severe: confluent bronchopneumonia

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34 LM: (1) a suppurative, neutrophil-rich exudates centered the bronchi, bronchioles, adjacent alveolar spaces (2) walls of bronchioles and alveoli: congestion,edema (3)surrounding: hyperemic edematous compensative emphysema (4)the abscesses are marked by necrosis of the underlying architecture

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37 complication (1)respiratory failure (2)heart failure (3)pyemia (4)abscess (5)bronchiectasis

38 Hypostatic pneumonia The patient with pulmonary edema from cardiac failure or heavy uremia, et al, is particularly vulnerable. Aspiration pneumonia The patient in coma or apoplexy, heavy anesthesia and so on is particularly vulnerable.

39 Viral pneumonia and mycoplasmal pneumonia They both belong to interstitial pneumonia Def. an inflammatory process involving the interstitial tissue of the lungs.

40 Etiology and pathogenesis pathogens: Most common: influenza virus A/B Less common: parainfluenza, respiratory syncytial virus ( especially in infants and children) Adenovirus common in army recruits Mycoplasmal pneumonia common among children and young adults Others: measles, chickenbox

41 Attachment of the organisms to the respiratory epithelium is followed by necrosis of the cells and an inflammatory response. Then, the inflammation extends to the interstitial tissue including peribronchial connective tissue and interalveolar septa.

42 Morphology Macroscopically: red-blue, congested, volume slightly enlarge and subcrepitant. little inflammatory exudates escapes on sectioning of the lung Histologically: the inflammatory process is largely confined within the walls of the alveoli. The septa are widened and edematous with a mononuclear infiltrate of lymphocytes, histiocytes and occasionally plasma cells. alveolar spaces are remarkably free of cellular exudate

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44 In virus infection, inclusion bodies may be formed within cytoplasm or nucleus of the epithelial cells of bronchioles and alveoli. In severe cases alveolar damage with hyaline membranes may develop.

45 viral inclusion body is round or oval shape, erythrocyte-like in size, eosinophilic cytoplasmic or nuclear

46 TYPES of PNEUMONIA LOBAR BRONCHO- PNEUMONIA Interstitial Distribution One or two lobes Scattered Scattered Cause Strept.Pneumoniae Multiple Bacteria Influenza/Mycoplasma Pathology Inflammation in alveolar wall cause consolidation. Pleuritis Inflam & purulent exudate in alveoli. Often from previous process Interstitial inflam. Around alveoli. Necrosis of bronchial epithelium Onset Sudden and acute Insidious Variable Signs High fever & chills Productive cough with rusty sputum. Progressive Rales to absence of sounds in affected lobe Mild fever. Productive cough with yellow-green sputum. Dyspnea Variable fever, headache. Aching muscles. Nonproductive hacking cough

47 TYPES of PNEUMONIA BRONCHOPNEUMONIA LOBAR PNEUMONIA

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49 Tuberculosis a communicable chronic granulomatous disease caused by Mycobacterium tuberculosis. After HIV, tuberculosis is the leading infectious cause of death in the world. Infection with HIV makes people susceptible to rapidly progressive tuberculosis; over 50 million people are infected with both HIV and M. tuberculosis. The lung is the most often affected organ.

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52 Basic pathological changes TB is a special type of inflammation. Alteration Exudation Proliferation

53 Alteration Grossly : gray- yellowish, massive caseation, consolidated Microscopically : red strained homogeneous amorphic material with cell debris sometimes or slightly granular material.

54 Caseous necrosis

55 Caseous necrosis

56 Exudative changes Early infections, numerous mycobecteria, high bacteria virulence, low host immunity and pronouned hypersensitivity. Sero-fibrinous inflammation, neutrophil cells, macrophages Location: lung, pleurea,

57 Proliferation Few organisms, low virulence and high host immunity. tubercle the most characteristic changes in tuberculosis

58 Tubercle (tuberculous granuloma) Typical tubercle consists of caseous necrosis in the center, surrounding it by the epithelioid and some Langhan s giant cells, with a peripheral aggregation of small lymphocytes and fibroblasts. The tubercle can be isolated or fuse to a large one. the epithelioid cells show a pale pink granular cytoplasm with indistinct cell boundaries, often appearing to merge into one another. The nucleus is less dense than that of a lymphocyte (vesicular), is oval or elongated and may show folding of the nuclear membrane.

59 Epithelioid cells

60 Tubercle nodules surrounding fibrosis

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62 Langhans giant cell

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64 Fate of the tuberculosis Healing of tuberculosis lesion Absorption and resolution. Fibrosis, fibrous encapsulation and calcification. Exacerbation of tuberculous lesions Infiltration and progression. Dissolution and dissemination.

65 primary tuberculosis secondary tuberculosis

66 Primary pulmonary tuberculosis the first infection TB more frequent in children, so called the childhood type TB, but primary lesion may also occurs in adult at a low rate of the tuberculosis.

67 Pathology Characteristic : Primary complex (the Ghon complex). Primary lesion (Ghon focus) Tuberculous lymphangitis Tuberculous lymphadenitis (in the hilar lymph nodes) X-ray : dumbbell-like

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69 Swelling of lymph nodes with caseous necrosis Primary focus with Caseous necrosis

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72 Clinical features Primary pulmonary tuberculosis is usually asymptomatic or manifested as a mild flu-like illness.

73 The fate of primary pulmonary TB In 95% of cases, immunity stops disease progression and healing occurs. small focus: resolution, fibrosis large focus: fibrous capsulation, calcification In 5% of cases, rapidly progressive pulmonary disease causing extensive caseous consolidation of the lung, usually occurs only in malnourished or immunodeficient children.

74 Three routes of dissemination 1.Bronchial dissemination----multiple foci 2.Lymphatic dissemination---hilar peribronchial cervical even distant lymph nodes 3.Hematogenous dissemination----miliary disease in lung or generalized military tuberculosis

75 Blood-borne dissemination: miliary tuberculosis Acute systematic/pulmonary miliary tuberculosis Numerous pale, translucent nodules in millet size are seen in lungs, kidneys, liver etc. Chronic systematic/pulmonary miliary tuberculosis

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81 Secondary pulmonary tuberculosis

82 Characteristic second infection adults bronchial dissemination infection from the apex downwards the course is usually protracted combination of old and fresh lesions proliferation is main lesions

83 Six types Focal pulmonary tuberculosis Infiltrative pulmonary tuberculosis Chronic fibro-cavernous pulmonary TB Caseous pneumonia Tuberculoma Tuberculous pleuritis

84 1. Focal tuberculosis The earliest lesions. most common site: lung apex number: one or more size: 0.5-1cm shape: well circumscribed, grayish white, yellow nature: mostly proliferative with central caseous necrosis and peripheral fibrosis Usually asymptomatic may calcify or quiescent form of infection or change into other types

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86 2. Infiltrative pulmonary tuberculosis (subclavicular lesion): most common type, Sputum infection-open TB (1)site: upper part of the lungs (subclavicular infiltration) (2)serofibrinous exudative lesions with central caseous necrosis (3) X-ray : cloudiness (4) tuberculous toxic symptoms and chronic cough, frequently with hemoptysis easily cured and short clinical course

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89 outcome a: healing b: progressive: enlargement, liquefaction, cavitation bronchogenic spread caseous pneumonia breaks through pleura-pneumothorax,tuberculosis pyopneumothoraxtransform into chronic fibro-cavernous TB

90 3. Chronic fibro-cavernous pulmonary TB (1) The upper lobes of lung contains multiple variant sizes, thick-walled chronic cavities. (2) Thicked cavity wall -- three components a. caseous necrosis b. tuberculous granulation tissue c. fibrous tissue (3) coexisting bronchial disseminated many tuberculous lesions and diffuse fibrosis in the pulmonary tissues. Later period, the lung becomes small, indurated,with pleural extensive adhesion, the function of the lung may be severely damaged.

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92 Tubercle cavity Old foci of TB New foci of TB

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95 Clinical feature Toxic:fever, night-sweat Respirator:cough, expectoration, hemoptysis, dyspnea, asphyxia breaks through pleura-pneumothorax, pyopneumothorax fibrosis -Cor Pulmonale

96 4. Caseous pneumonia May occur in debilitated immunodeficient or highly sensitized patients. Dissemination of large numbers of organisms in the focus via the bronchial tree, and spreading rapidly throughout large areas of lung parenchyma and producing a diffuse bronchopneumonia or lobar exudative consolidation ( galloping consumption ).

97 Pathological feature 1. Rapid serious condition of TB progression 2. One lobe or an entire lung affected and become consolidation 3. Severe exudation and severe necrosis 4. Serous exudate contain monocytes and lymphocytes in the alveoli 5. Young patients are more frequently affected

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103 5. Tuberculoma Definition: solitary globular caseous lesion surrounded by fibrosis Size: 2-5cm in diameter. Site: well delineated upper lobe X-ray: it is easily mistaken for tumor Tuberculomas represent quiescent disease.

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105 tuberculoma

106 6.Tuberculosis pleuritis According affected feature divide into: Moist tuberculous pleuritis (exudative tuberculous pleuritis) exudative inflammation (serious or serofibrinous). Heavy serious liquid hydrothorax. heavy fibrin formation thoracalgia. Dry tuberculous pleuritis (proliferative tuberculous pleuritis) This is a proliferative lesion dominate. Localized tubercles may form in the visceral pleura, and this may be followed by an tuberculous focus beneath pleura.

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111 Respiratory tumors Nasopharyngeal carcinoma Laryngocarcinoma Pulmonary carcinoma

112 Pulmonary carcinoma (Bronchogenic carcinoma) 95% of primary lung tumors arise from the bronchial epithelium. Undoubtedly, the bronchogenic carcinoma is the number one cause of cancer related deaths in industrialized cities.

113 Etiopathogenisis Smoking Air pollution Vocational factor Molecular genetic change

114 Morphology Types of gross: central type periphery type diffuse type

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119 Early stage pulmonary carcinoma: tumor mass <2cm, limited intrabronchi or infiltrated the bronchial wall and surrounding tissue, no metastasis in LN. Occult (concealed) carcinoama: cytologic smeares of sputum :tumor cells(+), clinic and X-ray(-), biopsy showed carcinoma in situ or early infiltrative carcinoma no metastasis in LN

120 Histologic classification (2003 WHO): squamous cell carcinoma small cell carcinoma adenocarcinoma large cell carcinoma adeno-squamous carcinoma sarcomatoid carcinoma carcinoid tumor salivary gland type carcinoma

121 Squamous cell carcinoma More common in men than women Tend to arise centrally in major bronchi and eventually spread to local hilar nodes Disseminate outside the thorax later than other histologic types Undergo central necrosis, cavitation Often preceded for years by squamous metaplasia/ dysplasia in the bronchial epithelium carcinoma in situ Atypical cells may be identified in cytologic smears of sputum or in bronchial lavage fluids or brushings, although asymptomatic and undetectable on radiographs

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123 squamous carcinoma

124 Small cell lung carcinoma(sclc) The five-year survival rate is only 1 to 2%. Derived from neuroendocrine cells of the lung, express a variety of neuroendocrine markers.

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127 Nests and cords of round to polygonal cell with scant cytoplasm, granular chromatin, and inconspicuous nucleoli.

128 Adenocarcinoma More common in women, and the association with smoking is weaker than for squamous cell carcinoma. usually peripherally located. grow slowly and form smaller masses than do other subtypes, but metastasize widely at an early stage.

129 Bronchioloalveolar carcinoma (BAC) A special type of adenocarcinoma.

130 BAC has a better prognosis than other bronchogenic carcinoma, the localized single mass has a 50 to 70% five-year survival rate, and the multifocal variant has a 20 to 25% five-year survival rate.

131 Large cell carcinoma A group of neoplasm that lack cytological differentiation and probably represent squamous carcinoma or glandular neoplasms that are too undifferentiated to permit categorization. Have a poor prognosis because of their tendency to spread to distant sites early. five-year survival rate is 2 to 3%.

132 Large cell carcinoma

133 Thanks!