Lungs

Alveolar epithelium, consisting of a continuous layer of two principal cell types: flattened, plate-like type I pneumocytes covering 95% of the alveolar surface; and rounded type II pneumocytes. The latter synthesize pulmonary surfactant and are the main cell type involved

in repair of alveolar epithelium after damage to type I pneumocytes.

loss of lung volumecaused by inaequate expansion of air spaces

• Incomplete expansion

• Collapse of alveoli

• Minor - accompany many pulmonary diseases

• Massive - less common

• Deficiency of surfactant-premature neonates- no functional maturity of lungs- pneumocytes II do not produce surfactant-

• Compression from outside - hart failure, pleuritis, tm of pleura, air

• Resorption of the air distal to bronchial

obstruction mucous plug, tumor, foreign

material

• Resorption atelectasis occurs when an obstruction prevents air from reaching distal airways. Any air present gradually becomes absorbed, and alveolar collapse follows

• The most common cause of resorption collapse is obstruction of a brnonchus.

Compression atelectasis is usually associated with accumulation of fluid, blood, or air within in the setting of congestive heart failure.

• Contraction atelectasis (or cicatrization atelectasis) occurs when local or diffuse fibrosis hamper lung expansion

• potentially reversible and should be treated promptly to

• Severe ARDS is characterized by rapid onset of lifethreatening respiratory insufficiency, cyanosis, and severe arterial hypoxemia that is refractory to oxygen therapy.

• The histologic manifestation of ARDS in the lungs is known as diffuse alveolar damage (DAD).

ARDS is a clinical syndrome of progressive respiratory

insufficiency caused by diffuse alveolar damage in the setting

of sepsis, severe trauma, or diffuse pulmonary infection.

Neutrophils and their products have a crucial role in the pathogenesis of ARDS by causing endothelial and epithelial injury.

The characteristic histologic picture is that of alveolar edema, epithelial necrosis, accumulation of neutrophils, and presence

of hyaline membranes lining the alveolar wall and ducts.

In the organizing stage, type II pneumocytes proliferate vigorously in an attempt to regenerate the alveolar lining. Resolution is unusual; more commonly, the fibrin-rich exudates organize into intraalveolar fibrosis

Most patients who survive the acute insult recover normal respiratory function within 6 to 12 months, but the rest develop diffuse interstitial fibrosis leading to chronic respiratory insufficiency

• Chronic bronchitis

• Emphysema

• Bronchiectasis

• Asthma

• In patients with these diseases, forced vitalCcapacity (FVC) is either normal or slightly decreased, while the expiratory flow rate

(FEV), is significantly decreased. + slower = obstruction

• The ratio of FEV to FVC is characteristically

decreased.

• By contrast, in diffuse restrictive diseases, FVC is reduced and the expiratory flow rate is normal or reduced proportionately. Hence, the ratio of FEV to FVC is near normal.

• Restrictive defects occur in two general conditions:

• chest wall disorders in the presence of normal lungs (e.g., with severe obesity, diseases of the pleura, and neuromuscular disorders, such as the Guillain-Barré syndrome

• acute or chronic interstitial lung diseases:

• The classic acute restrictive disease is ARDS

• Chronic restrictive diseases - pneumoconioses, interstitial fibrosis of unknown etiology, and infiltrative conditions such as sarcoidosis

permanent enlargement of air spaces distal to the terminal bronchoiles + destruction of their walls without significant fibrosis

central or proximal parts of acini are affected, disatl alveoli are spared

more in upper lobes -> apical segments

acini are uniformly enlarged

more commonly in the lower lung zones

associated with alpha 1 antirypsin deficience

• the proximal portion of the acinus is normal but the distal part is primarily involved.

• The emphysema is more striking adjacent to the pleura

• It occurs adjacent to areas of fibrosis, scarring, or atelectasis

  and is usually more severe in the upper half of the lungs.

• multiple, contiguous, enlarged air spaces ranging in diameter from less than 0.5 mm to more than 2.0 cm, sometimes forming cystic structures that, with progressive enlargement, give rise to bullae.

• The cause is unknown ,most often in young a14dults who present

acinus is irregulary involved, invariably involved with scarring

most common but clinically asymptomatic

• Protease-mediated damage of extracellular matrix has a central role in the airway obstruction seen in emphysema

• The idea that proteases are important is based in part on the observation that patients with a genetic deficiency of the anti-protease α1-anti-trypsin have a predisposition to develop pulmonary emphysema, which is compounded by smoking.

The diagnosis and classification of emphysema depend largely

on the macroscopic appearance of the lung.

Typical panacinar emphysema produces pale, voluminous lungs that often obscure the heart when the anterior chest wall is removed at autopsy.

The macroscopic features of centriacinar emphysema are less

impressive. Until late stages, the lungs are a deeper pink than

in panacinar emphysema and less voluminous

• Destruction of alveolar walls without fibrosis

• loss of elastic tissue in the surrounding alveolar septa, radial traction on the small airways is reduced

• As a result, they tend to collapse during expiration—animportant cause of chronic airflow obstruction in severeemphysema.

• Bronchiolar inflammation and submucosal fibrosis areconsistently present in advanced disease.

dyspnea (1.)

increased chest volume and relatively normal blood oxygenation at rest (pink puffers)

most patiens have signs andy symptoms of chronic bronchitis

2ndary pulmonary hypertension

barrel-chested and dyspnoic,

with obviously prolonged expiration,

sitting forward in a hunched- over position.

• Chronic bronchitis is diagnosed on clinical grounds: it is defined by the presence of a persistent productive cough for at least 3 consecutive months in at least 2 consecutive years

• It should be noted that emphysema is defined on the basis of morphologic and radiologic features, whereas chronic bronchitis is defined on the basis of clinical features

distinctive feature of chronic bronchitis is hypersecretion of mucus, beginning in the large airways

common among cigarette smokers and urban dwellers

cough raises mucoid sputum, but airflow is not obstructed

some have hzperresposive airways with intermitten bronchospasm and wheezing

especially heavy smokers, develop chronic outflow obstruction usually with associated emphysema (COPD).

• Asthma is a chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or early in the morning.

• Asthma has increased in incidence significantly in the Western world over the past 4 decades.

• Major factors contributing to the development of asthma include genetic predisposition to type I hypersensitivity (atopy), acute and chronic airway inflammation, and bronchial hyperresponsiveness to a variety of stimuli.

• hygiene hypothesis, according to which a lack of exposure to infectious organisms (and possibly nonpathogenic microorganisms as well) in early childhood results in defects in immune tolerance

• and subsequent hyperreactivity to immune stimuli later

most common type is type I IgE-mediated

begins in childhood

family history

attacks may be triggered by allergens in dust, pollen, anomal jair or food

skin test often used

RAST test for atopic

respiratory infections due to viruses and humoral and cellular mediators of airway obstruction

druf induced asthma -> aspirin

occupational asthma -> triggered by fumes organic or chemical dusts, gases

• The classic atopic form is associated with excessive type 2 helper T (TH2) cell activation.

• Cytokines produced by TH2cells account for most of the features of atopic asthma

• IL-4 and IL-13 stimulate IgE production,

• IL-5 activates eosinophils

• IL-13 also stimulates mucus production.

• IgE coats submucosal mast cells, which on exposure to allergen release their granule contents and secrete cytokines and other mediators.

• Mast cell–derived mediators produce two waves of reaction: an early (immediate) phase and a late phase

• occlusion of bronchi and bronchioles by thick, tenacious mucous plugs containing whorls of shed epithelium (Curschmann spirals).

• Numerous eosinophils and Charcot-Leyden crystals (crystalloids made up of the eosinophil protein galectin-10)

Thickening of airway wall

Sub-basement membrane fibrosis

Increased submucosal vascularity

An increase in size of the submucosal glands and goblet cell

• Metaplasia of the airway epithelium

• Hypertrophy and/or hyperplasia of the bronchial muscle

permanent dilation of bronchi and bronchioles caused by destruction of sm and supporting elastic tiss.

results from chronic necrotizing infections

not primary but secondary to persistent infection or obstruction

cough and expectoration of copinous amounts of prurlent sputum

• Chronic interstitial diseases are a

heterogeneous group of disorders characterized by bilateral, often patchy, pulmonary fibrosis mainly affecting the walls of the alveoli

• The hallmark of these disorders is reduced compliance (stiff lungs), which in turn necessitates increased effort to breathe dyspnea).

• there is frequent overlap in histologic features among the different conditions.

• The shared histologic features and the similarity in clinical signs, symptoms, radiographic alterations, and pathophysiologic changes justify their consideration as a group

• &Idiopathic Pulmonary Fibrosis

• unknown etiology

• progressive bilateral interstitial fibrosis.

• radiologic and histologic pattern is referred as usual interstitial pneumonia (UIP)

• not before 50 years

• males

• IPF is a diagnosis of exclusion.

Non specific interstitial pneumonia (NSIP).

• NSIP is a chronic bilateral interstitial lung disease of unknown etiology, which (despite its name) has distinct radiologic, histologic,and clinical features, including a frequent association with collagen vascular disorders such as rheumatoid arthritis.

• better prognosis than IPF

• It is characterized by mild to moderate interstitial chronic inflammation and/or fibrosis that is patchy but uniform in the areas involved.

• Pneumoconiosis is a term originally coined to describe lung disorders caused by inhalation of mineral dusts.

• the term has been broadened to include diseases induced by organic and inorganic particulates, and some experts also regard chemical fume- and vapor-induced lung diseases as pneumoconioses.

• Asbestos is a family of crystalline hydrated silicates with a fibrous geometry.

• exposure to asbestos is linked to:

• parenchymal interstitial fibrosis (asbestosis)>-

  • localized fibrous plaques, or, rarely, diffuse fibrosis in the pleura

• pleuraleffusions;

• lungcarcinoma

• malignant pleural and peritoneal mesothelioma

• laryngealcarcinoma

• when cristals are phygocytosed by macrophages, asbestos fibers activate the inflammasome & damage phagolysosomal membranes -> release of proinflammatory factors & fibrogenic mediators

• asbstos = tumor initiator & promotor

  
  

• asbestosis begins in the lower lobes and subpleurally, spreading to the middle andupper lobes of the lungs as the fibrosisprogresses.

• diffuse pulmonary interstitial fibrosis, characterized by the presence of asbestos bodies, which are seen as golden brown, fusiform or beaded rods with a translucent center.

Pleural plaques

-> well ircumscribed plaques of dense collagen often contain calcium

on the ant posterolat aspect of parietal pleura and over the dome sof the diaphram

• Sarcoidosis

• multisystemdi-seaseofunknownetiology characterized by noncaseating granulomatous inflammation in many tissues and organs.

• Although the etiology of sarcoidosis remains unknown, several lines of evidence suggest that it is a disease of disordered immune regulation in genetically predisposed individuals exposed to certain environmental agents

• A consistent predilection for adults younger than 40 years of age.

• A high incidence in Danish and Swedish populations, and in the United States among African Americans (in whom the frequency is 10 times higher than in whites).

A higher prevalence among nonsmokers, an association that is virtually unique to sarcoidosis among pulmonary diseases

Immunologic abnormalities

high levels of CD4+ TH1 cells in lung that secrete cytokines such as IFN-gamma

Hilar and paratracheal LN 75-9%

discrete, copact collection of epithelioid cells rimmed by an uter zone rich in CD4+ T cells

granulomas are replaced by diffuse intersitial fibrosis -> honey comb lung

(1) Schaumann bodies, laminated concretions composed of calcium and proteins

(2) asteroid bodies, stellate inclusions enclosed within giant cells.

Their presence is not required for diagnosis

the interstitium

tend to localize in the ct around bronchioles and pulmonary venulea in the pleura

erythema nodosum (skin lesions) -> in 25%

raised, red ,tender nodules on the anterior part of the legs

up to half of patients

• iritis or iridocyclitis

• choroiditis, retinitis, and optic nerve involvement

• sicca syndrome

• Combined uveoparotid involvement is designated Mikulicz sy

mostly asymptomatic and discovered by accident

2/3 of symptomatic cases there is a gradual apperance of respiratory symptoms shortness of breath, dry cough, or vague substernal discomfort) or constitutional signs and symptoms (fever, fatigue, weight loss, anorexia, night sweats).

• steroidtherapy

• Immunologically mediated inflammatory lung disease that primarily affects the alveoli- allergic alveolitis.

• occupational disease

• restrictive lung disease with the typical decreases in diffusion capacity, lung compliance, and total lung volumen

specific antibodies against the offending antigen int heir serum

• complement and immuoglobilins demonstrated in vessel walls by immunofluorescence

• bronchoalveolar lavage specimens show incrased CD4+ and CD8+

noncaseating granulomas found in the lungs of 2/3 of affected patients

peribronhciolar location

• Obstructive lung disease (COPD)

• Desquamative interstitial pneumonia (DIP)

• Respiratory bronchiolitis

-> acculumation of “smokers macrophages” in air spaces

-> alveola septa is thikened by inlfammatory infiltrate (lymphocytes)

-> instersitial fibrosis is mild

• Pulmonary Embolism • Hemorrhage

• Infarction

• Thromboembolism causes approximately 50,000 deaths per year in the United States and even when not directlyfatal often complicates the course of other diseases.

large deep veins of the leg

• prolonged bed rest (particularly with immobilization of the legs)

• surgery

• severetrauma

• congestiveheartfailure

• inwomen,useoforalcontraceptionpillswithhigh estrogen content;

• disseminatedcancer

• primarydisordersofhypercoagulability

size

increased pul. arterial pressure

ischemia

in saddle embolism ->sudden death

the higher the risk for infarction

the lower lobes & more than one half are multiple

• Most (60% to 80%) are clinically silent because they are small

• In 5% of cases, death, acute right-sided heart failure,or cardiovascular collapse (shock) occurs suddenly

• Obstruction of small to medium pulmonary branches (10% to 15% of cases) causes pulmonary infarction

rearly recurrent “showers” of emboli -> pul. hypertension, chronic right sided heart failure and pul. sclerosis with progressive worsening of dyspnea

25mm Hg or more at rest

caused by:

-> decrease in the cross-sectional area of the pulmonary vascular bed

-> increased pulmonary vascular blood flow

• Pulmonary arterial hypertension,

• Pulmonary hypertension due to left-sided heart disease

• Pulmonary hypertension due to lung diseases and/or hypoxia,

• Chronic thromboembolic pulmonary hypertension

• Pulmonary hypertension with unclear or multifactorial mechanisms

• idiopathic pulmonary arterial hypertension

plexiform lesion

the disease is advaced

• dyspnea and fatigue,

• respiratory distress, cyanosis,

• right ventricular hypertrophy appear, and death from decompensated cor pulmonale, often with superimposed thromboembolism and pneumonia, ensues within 2 to 5 years in 80% of patients.

• pneumonia -> any infection in the lung

• normally lung parenchyma remains strerile

  
  

• entrapment in the mucous blanket and removal by means of

  the mucociliary elevator

• phagocytosis by alveolar macrophages can kill and degrade

  organisms and remove them

• phagocytosis and killing by neutrophils recruited by macrophage factors

• complement may enter the alveoli and be activated by the alternative pathway to produce the opsonin C3b, which enhances phagocytosis;

• Organisms, including those ingested by phagocytes, may reach the draining lymph nodes to initiate immune responses

• Secreted IgA can block attachment of the microorganism to epithelium in the upper-respiratory tract;

  • serum antibodies (IgM, IgG) are present in the alveolar lining fluid and activate complement more efficiently by the classic pathway, yielding C3b

  • IgG is an opsonin

  • accumulation of immune T cells is important for controlling infections by viruses and other intracellular microorganisms.

• Inhalation of aerosol particles

• Aspiration of infected secretions from upper respiratory tract

• Aspiration of regurgitated gastric contents

• Hematogenous spread

• Bacteria – Streptococcus pneumoniae – Haemophilus influenzae – Staphylococcus aureus

• Viruses – influenza virus

• Fungi – Aspergillus flavus – Candida albicans – Pneumocystis carinii

• Bacteria-likeorganisms – Mycoplasma pneumoniae

patchy consolidation

slightly elevated, dry, granular, gray-red to yellow and poorly delimited at their margins

neutrophil rich exudate fills the bronchi, bronchioles and ajecent alveolar spaces

consolidation of a large portion of a lobe or of an entire lobe

1. congestion

2. red hepatization

3. gray hepatization

4. resolution

• vascular engorgement, intraalveolar fluid with few neutrophils, andoften the presence of numerous bacteria.

• massive confluent exudation, as neutrophils, red cells, and fibrin

• progressive disintegration of red cells and the persistence of afibrinosuppurative exudate resulting in a color change to grayish-brown.

• Systemic signs of infection—fever, chills, prostration

• Local signs of irritation—cough • Airway obstruction—shortness of breath

(dyspnea), rapid breathing (tachypnea)

• Inflammation and tissue destruction—expectoration of rusty sputum, hemoptysis

influenza types A and B and respiratory syncytial viruses

infection aquired in the course of hospital stay

-> S aureus

-> mostly in immunosupressed individuals

occurs in debilitated patients or those who aspirate gastric contents while unconscious (e.g., after a stroke) or during repeated vomiting.

ofeten necrotizing

frequent cause of death in the individual

localized area of suppurative necrosis within the pulmonary parenchyma, resulting in the formation of one or more large cavities

• Abscesses range in diameter from a few millimeters to large cavities 5 to 6 cm across.

• The localization-more common on the right side

• developed in the course of pneumonia or bronchiectasis

  commonly are multiple, basal, and diffusely scattered.

• Septic emboli and abscesses arising from hematogenous seeding are commonly multiple and may affect any region

• ruptures into airways or pleural cavity (pneumothorax, empyema)

• embolization of septic material to the brain, giving rise to meningitis or brain abscess

• Aspiration of infective material

• Aspiration of gastric contents

• Complication of necrotizing bacterial pneumonias

• Bronchial obstruction

• Septic embolism

• Hematogenous spread of bacteria

TBC

• Chronic pneumonia most often is a localized lesion in an immunocompetent individual, with or without regional lymph node involvement.

• In immunocompromised patients-widespread disease due to systemic dissemination of the causative organism

• Mycobacteria are slender rods that are acid-fast (i.e., they have a high content of complex lipids that readily bind the Ziehl-Neelsen [carbol fuchsin] stain and subsequently stubbornly resist decolorization).

• M. tuberculosis hominis

• most common cause of death resulting from a single infectious agent

delayed hypersensivity (tuberculin mantoux test)

• Entry into macrophages.

• Replication in macrophages.

• Development of cell - mediated immunity-approximately 3 weeks after exposure

• Under the influence of macrophage-secreted IL-12, CD4+ T cells of the TH1 subset are generated that are capable of secreting IFN-γ.

• T cell–mediated macrophage activation and killing of bacteria.

• TNF, which is responsible for recruitment of monocytes, which in turn undergo activation and differentiation into the “epithelioid histiocytes” that characterize the granulomatous response

• Elevate nitric oxide (NO) levels - particularly important in killing of mycobacteria;

• anti-microbial peptides (defensins) that are also toxic to mycobacteria

• • stimulating macrophages to kill mycobacteria, the TH1 response orchestrates the formation of granlomas and caseous necrosis.

• in unexposed patient

• normally doesnt lead to progessive primary tbc

• The inhaled bacilli usually implant in the distal air spaces of the lower part of the upper lobe or in the upper part of the lower lobe

• typically close to the pleura

• Ghon focus - 1-cm to 1.5-area of gray-white inflamatory consolidation

• combination of parenchymal and nodal lesions is called the

  Ghon complex

• Ghon complex undergoes progressive fibrosis, and calcification often follows (detectable as a Ranke complex on radiograph).

• Despite seeding of other organs, no lesions develop.

• in a previously sensitized host

• reactivation of dormant primary lesions many decades after initial infection, particularly when host resistance is weakened

• Reinfection

• localized to the apex of one or both upper

  lobes

• cavitation occurs readily

• initial lesion is small 2cm 1-2cm of the apical pleura

• may heal with fibrosis or might progess

• the apical lesion enlarges and the area of caseation expands.

• Erosion into a bronchus evacuates the caseous center, creating a ragged, irregular cavity lined by caseous

  material

• Erosion of blood vessels results in hemoptysis.

Miliary pulmonary disease occurs when organisms reach the bloodstream through lymphatic vessels and then recirculate to the lung via the pulmonary arteries

The lesions appear as small (2-mm) foci of yellow-white consolidation scattered through the lung parenchyma (the word miliary is derived from the resemblance of these foci to millet seeds).

With progressive pulmonary tuberculosis, the pleural cavity is invariably involved and serous pleural effusions, tuberculous empyema, or obliterative fibrous pleuritis

1. lymphatics -> in lung

2. blood -> meningitis, tbc of urogenital tracts, bone tbc

3. airways -> lung, larynx, aspired lead to intestinal Tbc

• Localized secondary tuberculosis may be asymptomatic.

• Manifestations are usually insidious in onset, with gradual development of both systemic and localizing symptoms and signs.

• malaise, anorexia, weight, loss, and fever.

• the fever is low grade and remittent (appearing late each afternoon and then

  subsiding),

• night sweat

• sputum, at first mucoid and later purulent

• when cavitation is present, the sputum contains tubercle bacilli.

• hemoptysis

• CULTUREremainsthestandarddiagnosticmodality because it can identify the occasional PCR-negative case and also allows testing of drug susceptibility

member of herpes virus

• pneumonitis,colitis,retinitis;thecentral

• nervous system usually is spared

• Infected cells are strikingly enlarged,

• often to a diameter of 40 μm, and exhibit cellular and nuclear pleiomorphism

• Prominent intranuclear basophilic inclusions spanning half the nuclear diameter are usually set off from the nuclear membrane by a clear halo

• congenital

• transmitted to the infant through cervical

• or vaginal secretions at birth, or later -(perinatal)

• through saliva.

• may occur through contact with respiratory secretions and by the fecal-oral route

• can occur at any age through organ transplantation or blood transfusion.

• P. jiroveci (previously P. carinii), an opportunistic infectious agent formerly considered to be a protozoan- now fungus

• patients with AIDS

• Intraalveolar foamy, pink-staining exudate with hematoxylin-eosin stain (“cotton candy” exudate)

• The septa are thicened by edema and aminimal mononuclear infiltrate

• Candida albicans is the most common disease-causing fungus.

• disease restricted to immunocompromised patients that has protean manifestations.

• The organisms may be visible with routine H&E

• Superficial infection on mucosal surfaces of the oral cavity, vaginitis,

  esophagitis, skin infection, chronic mucocutaneous candidiasis

• Invasive candidiasis- abscesse

95% of primary tumors are carcinomas -> most cancer deaths

most common malignant tumor of internal organs in the US

related to cigarette smoking -> polycyclic hydrocoarbons

poor prognosis

– Squamous dysplasia and carcinoma: precursor lesion for squamous-cell carcinoma.

– Adenomatous hyperplasia: precursor lesion for bronchioalveolar carcinoma, a form of adenocarcinoma.

– Idiopathic pulmonary neuroendocrine cell hyperplasia: precursor for pulmonary carcinoids.

1. irritation

2. carcinogens

3. initiaton

4. promotion

5. cancer

metapalsia -> dysplasia -> invasion

• Squamous cell carcinomas develop from a precancerous lesion proceeded by squamous metaplasia and squamous cell hyperplasia.

• These tumors generally grow in the central part of the lung in close relation to the large bronchi.

• Squamous cell carcinoma consists of cells that can produce keratin in the same way as normal squamous epithelial cells.

• Histochemically they tend to be TTF-1 negative, but positive for CK 5, 6 and P63

• consist of glandular t cellls producing mucus

• grow in peripheral part

• A special variant is adenocarcinoma in situ, previously named bronchoalveolar carcinoma

• Adenocarcinomas are positive for the thyroid transcription factor-1 (TTF-1). They also tend to be cytokeratin (CK) 7

  positive and CK 20 negative

• Adenocarcinomas ( tumor of any size with invasion >5 mm) are usually peripherally located, but also may occur closer to the hilum.

microinvasiveadenocarcinoma less than 5mm

• adenocarcinomas grow slowly and form smaller

masses than do the other subtypes, but they tend to

metastasize widely

• acinar (gland-forming), papillary; mucinous which is

often multifocal and may manifest as pneumonia-like consolidation); and solid types. most common

• involves peripheral parts of the lungs

• key feature of AIS diameter of 3cm or less, growth along preexisting structures and preservation of alveolar architecutre

• AIS does not demonstrate destruction of alveolar architecture or stromal invasion with desmoplasia

• small cells with high nucleo-cytolpasmic ration

• proliferate rapidly-> mitotic figures are present

• extensive necrosis

• Small tumor cells with a round to fusiform shape, scant cytoplasm, and finely granular chromatin with a salt and pepper appearance

• Similar to normal neuroendocrine cells, they contain neurosecretory granules that may produce peptide hormones and/or biogenic amines

• Stain positive for neuroendocrine markers

• Small cell lung cancers usually develop peribronchially and infiltrate the bronchial submucosa.

• Bronchial irritation: coughing,wheezing dyspnea, hemoptysis

• Local extension into the mediastinum or pleural cavity - pleural effusion-atelectasis, dispnea, pain, paralysis of diaphragm or vocal cords

• Apical neoplasms may invade the brachial or cervical sympathetic plexus, causing severe pain in the distribution of the ulnar nerve orHorner syndrome (ipsilateral enophthalmos,ptosis, miosis, and anhidrosis)

• Such apical neoplasms are sometimes called Pancoast tumors, and the combination of clinical findings is known as Pancoast syndrome.Pancoast tumor is often accompanied by destruction of the first andsecond ribs and sometimes the thoracic vertebrae.

• Involvement of the left supraclavicular node (Virchow node)

• Distant metastases : liver, brain, bone, adrenal gland

• Systemic effects of neoplasia: cachexia

• Paraneoplastic syndromes:

• Hypercalcemia-PTH

• Cushing-ACTH

• ADH

• Surgery • Surgical resection of the tumour and “some

normal tissue” around it.

• First line of choice for NSCLC who are medically fit to undergo surgery.

• Chemotherapy

• First line of treatment for SCLC, which are

  often disseminated upon clinical presentation.

• Also indicated for patients with more advanced stage of NSCLC (to improve survival, disease control or for palliative care).

• First line therapy for NSCLC with EGFRmutations involves targeted therapies.

• Hydrothorax- accumulation of the fluid in the pleural cavity

• Exudate - inflammation- bacterial pneuminia , TBC, ...

• Transudate - hart failure, generalised edema

• Chylothorax - pleural collection of a milky lymphatic fluid containing microglobules of

lipid.-cancer

• Serous pleuritis- resolution with no consequences

• Fibrinous or fobrinopurulent pleuritis-

destruction- granulation tissue- fibrous adhesions - fibrothorax

• Empyema – pus enclosed in fibrous adhesions

• Malignant effusions characteristically are large and frequently bloody (hemorrhagic pleuritis)

• Primary and secondary

• Benign - solitary fibrous tumor

• Mesothelioma

• Asbestos

often difficult to diagnose -> no characterisic symptoms

medical history important -> look for asbestos

physical examination, x-ray, lung function test

x-ray may reveal pleural thickening

CT or MRT

biopsy

1. epithelioid

2. sarcomatous

3. biphasic

calretinin importanat marker to distinguish mesothelioma from metastatic breast or lung cancer

• Metastatic adenocarcinoma

• Pleural sarcoma

• Synovial sarcoma

• Thymoma

• Metastatic clear cell renal cell carcinoma

• Metastatic osteosarcoma

radiation and chemotherapy

=> SURGERY (pleurectomie/decortication)

• common cold

• rhinoviruses

• acute bacterial epiglottis in children with H. influenza

• acute laryngitis can result from inhalation of irritants or may be caused by allergic reactions

• croup-laryngotracheobronchitits frightening inspiratory stridor and harsh, persistent cough. In occasional cases, the laryngeal inflammatory reaction may narrow the airway sufficiently to result in respiratory failure.

• EBV

• frequent in chinese people

• caracterized by large epithelial cells with indistict cell borders and prominent eosiophilic nucleoli

• often accompanied by T cells

• Etiology: tobacco and alcohol – abuse

• Combined - multiplicative model-young age- long duration

• Asbestosis?

• HPV-minor...but...

• GERD-increased risk

• nearly all cases occur in smokers, and alcohol and asbestos exposure also may play role

• Men

• HPV

• nonmalignant Lesions

• polyps on the true vocal cords-fibrous tissue and

  covered by stratified squamous mucosa

• laryngeal papilloma or sqamous papilloma slender, fingerlike projections supported by central fibrovascular cores and covered by an orderly, typical,stratified squamous epithelium

• recurrent respiratory papillomatosis (RRP)-(HPV) types 6 and 11.

• Hoarsenes

• Dysphagia

• Change of quality of voice

• Haemoptysis

• Glottic – up to60%,

• Supraglottic – up to 40%,

• Transglottic

• Infraglottic

• Plaque

• Polypoid

• Ulceration

• G1-3