Basic PATHOLOGY周 韧ZHOU REN

Prof., M.D., Ph.D.

Department of Pathology & Patho-physiology Institute of Pathology & Forensic Medicine

Zhejiang University Judicial Evidence & Evaluation Center

Zhejiang University School of Medicine

zhouren@zju.edu.cn

http://doc.zju.edu.cn/blx/

Respiratory Diseases

Review of the architecture of the respiratory

system

PULMONARY DUCT PULMONARY ACINUS

Bronchus Bronchioles Respiratory bronchiBronchus Bronchioles Respiratory bronchioles Alveolar duct Alveolar cyst Alveolusoles Alveolar duct Alveolar cyst Alveolus

Acute bronchitisAcute bronchitis EmphysemaEmphysema

Chronic bronchitis Chronic bronchitis Asthma Asthma

BronchiectasisBronchiectasis

Bronchiolar Bronchiolar pneumonia pneumonia

Lobular Lobular pneumonia pneumonia

SquamousSquamous cell carcinoma cell carcinoma AdenocarcinomaAdenocarcinoma

BronchioloalveolarBronchioloalveolar carcinoma carcinoma

Pulmonary tuberculosisPulmonary tuberculosis

Pneumonia

Pneumonia can be very broadly Defined as any infection in the lung. Pathologically, it may be defined as any inflammation of lung.

Classification of pneumonia

1. Etiological classification:bacterial pneumoniaviral pneumoniafungal pneumonia etc.

2. Anatomical classification:lobar pneumonialobular pneumoniainterstitial pneumonia.

Clinically, etiological classification is more beneficial to the treatment; but the etiological classification usually can not be made readily.

The anatomical classification may give a great help to the etiological diagnosis sometimes.> 90%: caused by Streptococcus pneumoniae (pneumococcus) ;

interstitial pneumonia are caused by virus or mycoplasm.

Bacterial Pneumonia

Lobar pneumoniaDef.In lobar pneumonia the contiguous air spaces of part or all of a lobe are homogenously filled with an exudates that can be visualized on radiographs as a lobar or segmental consolidation and is thus sometimes referred to as “air space” pneumonia.

The disease which is often seen in previouslyhealthy young adults has a sudden onset and is accompanied by chills, fever , cough with pink-foam sputa and chest-ache.

Etiology and pathogenesis

>90% S. pneumonia enter the lungs via the airways

Occasionally other organisms (Klebsiella pneumoniae,

staphylococci, streptococci, Haemophilus influenzae).

Lobar pneumonia is initiated in periphery acinus, from there the exudative fluid containing etiologic agent flows into the adjacent air passage to infect adjacent lobules until a segment or entire lobe is infected.

MorphologyFor purposes of description, it is convenient to divide the process into four phases:

(1) Congestion(2) Red hepatizatio (consolidation)(3) Gray hepatization(4) Resolution

1. Congestion stage (1st-2nd days)

The affected lobe is heavy, red and boggy. A frothy blood-stained fluid can be squeezed from the cut surface.

Histologically, there is vascular congestion with proteinaceous fluid, scattered neutrophils, and many bacteria in the alveoli.

Clinically, the onset is sudden with fever and rigors.

2. Red hepatization stage(2nd-4th day)

Liver-like in consistencySeptal capillaries are congested markedly

Alveolar spaces are packed with many red cells, andseveral neutrophils, fibrin.

The pleura usually demonstrates a fibrinous or fibrinopurulent exudates.

3. Gray hepatization stage(4th –8th day)

More solid in consistencyPleural surface is covered with a confluent fibrinous exudates.

The cut surface is dry and granular but of a grayish-white color.

Histologically, congestion of septalcapillaries lightens. The fibrinous exudatepersists within the alveoli and a fibrin netforms. There are many neutrophils but is relatively depleted of red cells in the alveoli.

4. Resolution stage(8th-9th day)

With the elimination of bacteria, the inflammation subsides. Since there is no tissue destruction the lung return to normal apart from the pleura.

X光肺叶密度增高

肺叶实变

Complications:1. Carnification: Organization of intraalveolar fibrinous exudates instead of resorption may 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.

Bronchopneumonia

Conception: Defined as an acute purulent inflammation characterized by diffuse patchy pneumonic consolidation often with bronchiolitis in its center.

It is a threat chiefly to the vulnerable infants, the aged, and those suffering from chronic debilitating illness or immuno-suppression.

Children: Whooping cough and measles are important antecedents

Adult: influenza, chronic bronchitis, alcoholism, malnutrition, and carcinomatosis are all predisposing conditions.

Clinically, bronchopneumonia may appears as a complication of a disease.

Hypostatic pneumoniaThe patient with pulmonary edema from cardiac failure or heavy uremia, et al, is particularly vulnerable, who are necessary to keep themselves in bed in prolonged time.

Aspiration pneumoniaThe patient in coma or apoplexy, heavy anesthesia and so on is particularly vulnerable.

Almost any organism may cause bronchopneumonia, frequent offenders are staphylococci, streptococci, haemophilus influenza, proteus species etc.

Etiology

Foci of inflammatory consolidation with a center of bronchiolitis are distributed in patches through one or several lobes, most frequently bilateral and basal.

Morphology

Well-developed lesions up to 3 or 4 cm (usually 0.5-1 cm) in diameter are slightly elevated, dry, granular, gray-red to yellow and demarcated distinctly.

The lung substance immediately surrounding areas of consolidation is usually hyperemic and edematous, but the large intervening areas are generally normal.

Histologically, the reaction consists of a suppurative exudates that fills the bronchi,bronchioles, and adjacent alveolar spaces.

Hyperemia, edema and inflammatary infiltration can be seen in the walls of bronchioles.

ComplicationThe same complication, as in

lobar pneumonia.

Viral pneumonia and mycoplasmalpneumonia

They both belong to interstitial pneumonia

Def. an inflammatory process involving the interstitial tissue of the lungs.

Etiology and pathogenesis

The common agents are viruses and mycoplasma.

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 tissueincluding peribronchial connective tissue and interalveolar septa.

MorphologyMacroscopically: red-blue, congested, and

subcrepitant. Because much of the reaction is interstitial, little inflammatory exudates escapes on sectioning of the lung, although there may be slight oozing of red, frothy fluid.

Histologically, the inflammatory process is largely confined within the walls of the alveoli. The septa are widened and edematous; they usually contain a mononuclear infiltrate of lymphocytes, histiocytes and occasionally plasma cells.

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.

A TRY

Chronic obstructive pulmonary disease (COPD)

chronic bronchitisemphysema

bronchial asthmabronchiectasis

Chronic bronchitis

Def. A persistent productive cough for at least three consecutive months in at least two consecutive years.

Etiology and Pathogenesis

smoking, air pollution (SO2, NO2)

hypersecretionof bronchial mucous gland

hypertrophy of mucous gland, Goblet cell metaplasiaof bronchial

epithelium

directly or through neurohumoralpathways

chronic bronchitis

loss of ciliated epithelium

retention of secretion

proliferation of bacteria

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↓ ↙

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microbial infection

Morphology

Grossly ①mucosal lining of the larger airways is usually hyperemic and swollen by edema fluid; ②it is covered by a layer of mucinous or mucopurulent secretions. The smaller bronchi and bronchioles may also be filled with similar secretions.

3. 病理变化

部位

主要特征

眼观:早期

进展

Histologically:Hypertrophy of mucous gland and goblet cell metaplasia of bronchial wall.

镜检:(1)腺体肥大, 分泌亢进

后期腺体萎缩, 分泌耗竭(2)气管粘膜上皮细胞的损伤(3)支气管壁的病变

①the diagnostic feature : enlargement of the mucus-secreting glands.

Reid index: the ratio of the thickness of the submucosal gland layer to that of the bronchial wall .Normal : 1:3

Chronic bronchitis : usually exceeds 1:2.

粘液腺肥大、增生; 浆液腺发生粘液化生。

粘液腺增生肥大

粘液分泌亢进

上皮鳞化

②Increased number of goblet cells in the lining epithelium with concomitant loss of ciliated epithelial cells.

③squamous metaplasia of lining epithelium followed by dysplasticchanges.

④ Mucosal and submucosal lining of bronchi are hyperemic and swollen . inflammatory infiltration (lymphocytes , plasmacytes, sometimes admixed with neutrophils).

支气管粘膜慢性炎伴上皮鳞状化生

Complications

1. Emphysema2. cor pulmonals3. Bronchiectasis4. Bronchopneumonia5. bronchogenic carcinoma of lung

EmphysemaDef. characterized by abnormal permanent

enlargement of the air space distal to the terminal bronchiole accompanied by destruction of their walls.

Etiology1. Alveolar wall destruction and air space enlargement invokes excess protease or elastase activity unopposed by appropriate antiprotease regulation

①Increase either the number of PMN and MP in the lung

②Increase release of protease from PMN and MP

③ oxidants in cigarette smoke and O2

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radicals secreted by PMN & MP inhibit the active of α1-AT and decrease net anti-elastase activity in smokers

Antiprotease α1-antitrypsin inhibition

α1-antitrypsin DeficiencyPiMM/PiZZ (Chr14)

Smoking

↑Protease : elastase collagenase

Destruction of elastin and collagen of the lung

Emphysema

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2. Obstruction of the bronchioles.

Air enter into the alveoli distal to the obstructed bronchiole through Kohn’s pore (interalveolar pore), and air is trapped during expiration because the pore is closed. Emphysema is ended.

（四） 病因与发病机理

(1)病因

(2)发病的二个基本环节

细支气管阻塞和狭窄

小气道及肺泡支撑组织的破坏

Classification and MorphologyAlveolar emphysema: centriacinar emphysema

panacinar emphysemaperiacinar emphysema

Interstitial emphysema:Others: paracicatrical emphysema

bullae lungsenile emphysemacompensatory emphysema

Diagram of the fundamental unit of the lungcentriarclinal and panacinar emphysema.

MorphologyThe lesions of centriacinar emphysema are

more common and severe in the upper lobes particularly in the apical segments.

腺泡中央型肺气肿

Panacinar emphysema:

pale, voluminous lungs

全腺泡型肺气肿

Microscopic features:

1. Thinning and destruction of alveolar walls. 2. Adjacent alveoli become confluent, creating large air spaces. 3. Capillaries in alveolar septa decreased.

Terminal and respiratory bronchioles may be deformed because of the loss of septa.

BullousBullous emphysemaemphysema

囊泡型肺气肿（大泡直径3cm）

Conditions related to emphysema.There are several conditions in which enlargement of air spaces is not accompanied by destruction; this is more correctly called overinflation.

Compensatory emphysema Senile emphysema

Interstitial emphysema designates the entrance of air into the connective tissue of the lung, mediastinum and subcutaneous tissue.

This may occur spontaneously with a sudden increase in intraalveolar pressure (as with vomiting or violent coughing) that cause a tear, with dissection of air into the interstitium.

Complications:

1. Cor pulmonale2. Pneumothorax3. Respiratory failure

BronchiectasisDef. Permanent dilatation of bronchi and

bronchiole due to destruction of the muscle and elastic supporting tissue.

The characteristic symptom:cough and expectoration of copious amounts of

purulent sputum.

Etiology and pathogenesis

Bronchial obstruction (tumor, enlarged lymph node, foreign body)

rise of intrabronchialpressure during respiration

bronchial dilatation

infection

loss of ciliated epithelium

retention of secretion

cough

congenital or hereditoryconditions

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Weakening and loss of

elastic tissue ，muscle and

cartilage of bronchus ↘

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MorphologyGrossly: usually affects the lower lobes

bilaterally, particularly those air passages that are most vertical.

The airways may be dilated as much as 4 times their usually diameter and can be followed nearly to the pleural surfaces.

(By contrast, in normal lungs the bronchioles cannot be followed by ordinary gross examination beyond a point 2 to 3 cm from the plural surface.)

Patterns of dilatation:cysticcylindrical

①there is an intense acute and chronic inflammatory exudates within the wall of the bronchi and bronchioles and desquamation of lining epithelium leaving extensive areas of ulcerated epithelium.

Histologically,

②there may be squamous metaplasia of the lining epithelium.

③In some instances, the necrosis destroys the bronchial or bronchiolar walls and forms a lung abscess.

④When healing occurs, granulation tissue forms the base of ulcer.

Clinicopathological correlation

1. Postural coughing with large quantity of pus.2. hemoptysis due to erosion of the vessel in

granulation tissue.

Complications

1. lung abscess2. Pyemia--metastatic abscesses3. Pulmonary fibrosis and cor pulmonale.