Robbins Chapter 13 - The Lung

Front 1

How do you differentiate bronchi from bronchioles?

Back 1

Bronchi have cartilage and submucosal glands within the walls

Front 2

What is the acinus (lung anatomy)?

Back 2

The part of the lung distal to the terminal bronchiole - composed of respiratory bronchioles that proceed into alveolar ducts and alveolar sacs

Front 3

Describe the microscopic composition of the alveolar walls.

Back 3

Capillary endotheliumBasement membrane and surrounding interstitial tissueAlveolar epitheliumAlveolar macrophages

Front 4

What cells compose the pulmonary interstitium?

Back 4

Fine elastic fibers, small bundles of collagen, a few fibroblast-like cells, smooth muscle cells, mast cells, rare mononuclear cells

Front 5

What are alveolar macrophages?

Back 5

Mononuclear cells of phagocytic lineage, usually lying free within the alveolar space. Often contain phagocytosed carbon particles.

Front 6

What cell types are found in alveolar epithelium?

Back 6

Two principal cell types - type I pneumocytes, type II pneumocytes

Front 7

What is the difference between Type I pneumocytes and Type II pneumocytes?

Back 7

Type I pneumocytes are flattened, platelike cells covering 95% of the alveolar surfaceType II pneumocytes are rounded, and are the source of pulmonary surfactant. They are the main cell type involved in repair of alveolar epithelium when type I cells are damaged.

Front 8

What are pores of Kohn?

Back 8

Pores between the alveolar walls which permit passage of bacteria and exudates between adjacent alveoli

Front 9

What are the three divisions into which lung diseases are organized?

Back 9

Lung diseases that affect...The airwaysThe interstitiumThe pulmonary vascular system

Front 10

What is atelectasis?

Back 10

Also known as collapse - loss of lung volume caused by inadequate expansion of airspaces.

Front 11

What processes occur following atelectasis?

Back 11

Inadequate expansion of airspaces results in shunting of inadequately oxygenated blood from pulmonary arteries into veins - giving rise to a ventilation-perfusion imbalance and hypoxia.

Front 12

What are the three forms of atelectasis?

Back 12

Resorption atelectasisCompression atelectasisContraction atelectasis

Front 13

What is resorption atelectasis?

Back 13

Occurs when an obstruction prevents air from reaching distal airways. The air already present becomes absorbed and alveolar collapse follows.

Front 14

What is the most common cause of resorption atelectasis?

Back 14

Obstruction of a bronchus by a mucous or mucopurulent plug - frequently occurs postoperatively but may also complicate bronchial asthma, bronchiectasis, chronic bronchitis, or aspiration of foreign bodies.

Front 15

What is compression atelectasis?

Back 15

Sometimes called passive or relaxation atelectasis - usually associated with accumulations of fluid, blood, or air within the pleural cavity - mechanically collapses the adjacent lung.

Front 16

What may cause compression atelectasis?

Back 16

Pleural effusions (CHF)Pneumothorax - air leaks into the pleural cavityBasal atelectasis from elevated position of the diaphragm in bedridden patients, patients with ascites, and pre/post-op

Front 17

What is contraction atelectasis?

Back 17

Also known as cicratization - occurs when either local or generalized fibrotic changes in the lung or pleura hamper expansion and increase elastic recoil during expiration.

Front 18

Which forms of atelectasis are reversible? Irreversible?

Back 18

Contraction atelectasis - irreversibleCompression atelectasis - reversibleResorption atelectasis - reversible

Front 19

How does acute lung injury manifest clinically?

Back 19

Acute onset of dyspneaDecreased arterial oxygen pressure (hypoxemia)Development of bilateral pulmonary infiltrates on radiographsAbsence of clinical evidence of primary left-sided heart failure

Front 20

What is ARDS?

Back 20

Acute Respiratory Distress Syndrome

Front 21

What are the basic causes of ARDS?

Back 21

Diffuse alveolar capillary and epithelial damage, resulting from an imbalance of pro-inflammatory and anti-inflammatory mediators.Associated with either direct injury to the lung or indirect injury in the setting of a systemic process.

Front 22

Describe the onset of ARDS

Back 22

Rapid onset of life threatening respiratory insufficiencyCyanosisSevere arterial hypoxemia that is refractory to oxygen therapyProgression to multisystem organ failure

Front 23

What is the histological manifestation of ARDS?

Back 23

Diffuse alveolar damage - DAD

Front 24

What are the two barriers forming the alveolar capillary membrane?

Back 24

Microvascular endotheliumAlveolar epithelium

Front 25

What are the acute consequences of damage to the alveolar capillary membrane?

Back 25

Increased vascular permeabilityAlveolar floodingLoss of diffusion capacityWidespread surfactant abnormalities from type II pneumocyte damage

Front 26

What transcriptional factor may play a large role in shifting the pro/anti-inflammatory balance in favor of a pro-inflammatory state?

Back 26

Nuclear factor kB (NF-kB)

Front 27

What are some indirect causes of lung injury which may result in ARDS?

Back 27

Commonly - Sepsis, severe trauma with shockUncommonly - Cardiopulmonary bypass, acute pancreatitis, drug overdose, transfusion of blood products, uremia

Front 28

What are some direct causes of lung injury which may result in ARDS?

Back 28

Commonly - Pneumonia, Aspiration of gastric contentsUncommonly - Pulmonary contusion, fat embolism, near-drowning, inhalation injury, reperfusion injury after lung transplantation

Front 29

How do pulmonary macrophages react in ARDS?

Back 29

Pulmonary macrophages - increased synthesis of IL-8 (neutrophil chemotaxis, activator)IL-1 and TNF are also released, which lead to endothelial activation

Front 30

In acute phase of ARDS, what is the gross appearance of the lungs?

Back 30

Dark red, firm, airless, heavy

Front 31

What are the microscopic findings in the lungs in acute ARDS?

Back 31

Capillary congestionNecrosis of alveolar epithelial cellsInterstitial and intra-alveolar edema and hemorrhageCollections of neutrophils in capillariesHyaline membranes, especially lining the alveolar ducts

Front 32

What is seen microscopically in the organizing stage of ARDS?

Back 32

Marked proliferation of type II pneumocytes in an attempt to regenerate the alveolar liningOrganization of fibrin exudates with intra-alveolar fibrosisThickening of alveolar septa, and proliferation of interstitial cells with deposition of collagen

Front 33

How soon after the original lung event does the clinical syndrome of ARDS present?

Back 33

85% of patients present with ARDS within 72 hours of precipitating event

Front 34

What is the current prognosis for ARDS?

Back 34

About 60% mortality rate

Front 35

What are some factors which predict a poor outcome with ARDS?

Back 35

Advanced ageUnderlying bacteremia (sepsis)Development of multisystem failure (especially cardiac, renal, or hepatic)

Front 36

If a patient survives the acute stage of ARDS, what sequela may be present?

Back 36

There may be diffuse interstitial fibrosis, which may continue to compromise respiratory function.

Front 37

If a patient survives ARDS without any chronic sequela, how long does it take to regain normal respiratory function?

Back 37

6-12 months

Front 38

What are the two categories of diffuse pulmonary diseases?

Back 38

Obstructive disease (airway disease)Restrictive disease

Front 39

What characterizes obstructive disease (airway disease)?

Back 39

Characterized by limitation of airflow, usually resulting from an increase in resistance caused by partial or complete obstruction at any level

Front 40

What characterizes restrictive disease?

Back 40

Characterized by reduced expansion of lung parenchyma accompanied by decreased total lung capacity.

Front 41

What are the major diffuse obstructive disorders of the lungs?

Back 41

EmphysemaChronic bronchitisBronchiectasisAsthma

Front 42

What changes are seen in TLC and FVC in diffuse obstructive disorders? WHat is the hallmark?

Back 42

TLC and FVC are either normal are increasedHallmark - decreased expiratory flow rate, measured by forced expiratory volume at 1 second (FEV1)The ratio of FEV1 to FVC is characteristically decreased

Front 43

What are the physiological causes of expiratory obstruction in diffuse obstructive disorders?

Back 43

May be from anatomic airway narrowing, classically observed in asthma, or loss of elastic recoil (emphysema)

Front 44

What is the FVC and FVC/FEV1 ratio in diffuse restrictive lung diseases?

Back 44

FVC is reduced and expiratory flow rate is normal or reduced proportionallyAs ar esult, the ratio of FEV1/FVC is near normal

Front 45

What kinds of conditions may cause diffuse restrictive lung diseases?

Back 45

Chest wall disorders in the presence of normal lungs - severe obesity, diseases of the pleura, neuromuscular disorders (Guillan-Barre)Acute or chronic interstitial lung diseases (ARDS)

Front 46

What are some chronic restrictive lung diseases?

Back 46

PneumoconiosesInterstitial fibrosis of unknown etiologyInfiltrative conditions (sarcoidosis)

Front 47

What are the main pathological changes in chronic bronchitis?

Back 47

Mucus gland hyperplasiaHypersecretion

Front 48

What causes chronic bronchitis and what are the major S/S?

Back 48

Caused by tobacco smoke, air pollutantsS/S: Cough, sputum production

Front 49

What are the main pathological changes in Bronchiectasis?

Back 49

Airway dilationScarring

Front 50

What causes Bronchiectasis? What are the major S/S?

Back 50

Caused by persistent or severe infectionsS/S: Cough, purulent sputum, fever

Front 51

What are the main pathological changes in Asthma?

Back 51

Smooth muscle hyperplasiaExcessive mucusInflammation

Front 52

What are the main causes of Asthma? S/S?

Back 52

Caused by immunological or undefined problemsS/S: Episodic wheezing, cough, dyspnea

Front 53

What are the major pathological changes in emphysema?

Back 53

Airspace enlargementWall destruction

Front 54

What are the main pathological changes in small-airway disease, bronchiolitis?

Back 54

Inflammatory scarringObliteration of bronchioles

Front 55

How does one differently define emphysema and chronic bronchitis?

Back 55

Emphysema is defined by its specific morphologyChronic bronchitis is defined on the basis of clinical features such as the presence of chronic and recurring cough with excessive mucus secretion.

Front 56

Where is emphysema localized anatomically compared to chronic bronchitis?

Back 56

Chronic bronchitis affects both the large and small airways (if small then bronchiolitis)Emphysema is restricted to the acinus (respiratory bronchiole, alveolar ducts and alveoli)

Front 57

How many individuals in the US have COPD? How significant is it as a cause of death?

Back 57

10% of people in the US have COPDIt is the 4th leading cause of death in the US

Front 58

Is COPD reversible or irreversible?

Back 58

Irreversible

Front 59

What characterizes Emphysema?

Back 59

Abnormal permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls without obvious fibrosis.

Front 60

What are the four types of emphysema?

Back 60

CentriacinarPanacinarDistal acinarIrregular

Front 61

What is centracinar (centrilobular) emphysema?

Back 61

This pattern involves the lobules - the central or proximal parts of the acini, formed by respiratory broncioles, are affected, while distal alveoli are spared.As a result, emphyesmatous and normal airspaces exist within the same acinus and lobule. More common and severe in the upper lobes, particularly the apices.

Front 62

Which type of emphysema is most commonly seen as a consequence of smoking cigarettes (without congenital deficiency of alpha-1 antitrypsin)?

Back 62

Centracinar (centrilobular) Emphysema

Front 63

Which type of emphysema is most common in those with congenital deficiency of alpha-1 antitrypsin?

Back 63

Panacinar (Panlobular) Emphysema

Front 64

What is panacinar (panlobular) emphysema?

Back 64

The acini are uniformly enlarged from the level of the respiratory bronciole to the terminal blind alveoli - tends to occur more commonly in the lower lung lobes and in individuals with alpha-1 antitrypsin congenital deficiency.

Front 65

What is distal acinar (paraseptal) emphysema?

Back 65

The proximal portion of the acinus is normal but the distal part is primarily involved. The emphysema is more striking adjacent to the pleura, along the lobular connective tissue septa, and at the margins of the lobules. It tends to occur adjacent to areas of fibrosis, scarring, or atelectasis and is usually more severe in the upper half of the lungs.

Front 66

What are some characteristic findings in distal acinar (paraseptal) emphysema?

Back 66

Multiple, contiguous enlarged airspaces that range in diameter from 0.5 to more than 2.0 cm, sometimes forming cyst-like structures with progressive enlargement - bullae.

Front 67

In which individuals is distal acinar (paraseptal) emphysema more common?

Back 67

This type probably underlies many of the cases of spontaneous pneumothorax in young adults.

Front 68

What is irregular emphysema?

Back 68

It is "irregular" because the acinus is irregularly involved - almost always associated with scarring - resulting from healed inflammatory diseases. Though clinically asymptomatic, may be the most common form of emphysema.

Front 69

What is the most common form of emphysema, though usually it is asymptomatic?

Back 69

Irregular emphysema

Front 70

What critical imbalances favor the development of emphysema?

Back 70

The protease-antiprotease imbalanceOxidant-antioxidant imbalance

Front 71

Describe the protease-antiprotease imbalance hypothesis with regards to emphysema.

Back 71

Patients with genetic deficiency of antiprotease alpha-1 antitrypsin, a major inhibitor of proteases secreted by neutrophils, have a greater chance of developing pulmonary emphysema.

Front 72

What percentage of individuals homozygous for Z allele (and thus deficiency of alpha-1 antitrypsin) develop sympatomatic emphysema?

Back 72

More than 80%

Front 73

Describe the pathogenesis of emphysema.

Back 73

Neutrophils and macrophages accumulate in alveoli, in smokers or from other stimuli. NF-kB is activated, resulting in production of TNF and chemokines like IL-8, which attract and activate more neutrophils.Neutrophils release their granules which include proteases, resulting in tissue damageElastase activity in macrophages is enhanced by smoking as well

Front 74

How does smoking propagate the oxidant-antioxidant imbalance? Describe the pathogenesis with regards to emphysema.

Back 74

Smoking depletes the lung's natural reservoirs of antioxidants (superoxide dismutase, glutathione) Tissue damage occurs from oxidant materialsActivated neutrophils add to the pool of ROS in the alveoliInactivation of native antiproteases occurs, resulting in "functional" alpha-1 antitrypsin deficiency

Front 75

How does emphysema progress clinically?

Back 75

Dyspnea is the first symptom - also cough and wheezing of patients also have chronic bronchitis or asthmatic bronchitisWeight loss is common and may be severePFTs reveal reduced FEV1 and normal or near FVC - hence the ratio of FEV1 to FVC is reduced.Barrel chest (increased AP diameter)"Pink puffers"

Front 76

Describe an emphysema presentation described as "blue bloaters".

Back 76

Patients have emphysema and pronounced chronic bronchitis - history of recurrent infections with purulent sputumLess prominent dyspnea and respiratory drive, so hypoxic, cyanoticTend to be obese and first medical visit associated with CHF (cor pulmonale) and edema

Front 77

How does secondary pulmonary hypertension develop in patients with emphysema?

Back 77

It is a gradual onsetIt arises from both hypoxia-induced pulmonary vascular spasm and loss of pulmonary capillary surface area from alveolar destruction

Front 78

When emphysema results in death, what specific sequelae of emphysema may be primarily responsible?

Back 78

Right-sided heart failure (cor pulmonale)Pulmonary failure with Respiratory acidosis, Hypoxia, Coma

Front 79

What is compensatory emphysema?

Back 79

A term used to designate the compensatory dilation of alveoli in response to loss of lung substance elsewhere - occurs in residual lung parenchyma after surgical removal of a diseased lung or lobe

Front 80

What is obstructive overinflation?

Back 80

Results when the lung expands because air is trapped within it - a common cause is subtotal obstruction by a tumor or foreign object. May be a life-threatening emergency

Front 81

What is bullous emphysema?

Back 81

Any form of emphysema that produces large subpleural blebs or bullae. Bullae are localized accentuations of one of the four forms of emphysema, are often subpleural, and may rupture leading to pneumothorax.

Front 82

What is mediastinal (interstitial) emphysema?

Back 82

Designates the entrance of air into the connective tissue stroma of the lung, mediastinum, and subcutaneous tissue. May occur spontaneously with sudden increase in intra-alveolar pressure (as with vomiting or violent coughing) that causes a tear with dissection of air into the interstitium.

Front 83

How may a patient present with mediastinal (interstitial) emphysema?

Back 83

Marked swelling of the head and neck and crackling crepitation all over the chest.

Front 84

How is chronic bronchitis defined?

Back 84

A persistent productive cough for at least 3 consecutive months in at least 2 consecutive years.

Front 85

What are the three general forms of bronchitis?

Back 85

Simple chronic bronchitisChronic asthmatic bronchitisChronic obstructive bronchitis

Front 86

What is simple chronic bronchitis?

Back 86

The productive cough raises mucoid sputum but airflow is not obstructed

Front 87

What is chronic asthmatic bronchitis?

Back 87

Hyper-responsive airways with intermittent bronchospasm and wheezing

Front 88

What is chronic obstructive bronchitis?

Back 88

A subpopulation who develops chronic outflow obstruction, usually with evidence of associated emphysema

Front 89

What is the distinctive characteristic of chronic bronchitis?

Back 89

Hypersecretion of mucus

Front 90

Describe the pathogenesis of chronic bronchitis.

Back 90

An irritant such as cigarette smoke or sulfur dioxide induces hypertrophy of mucous glands in the trachea and main-stem bronchiIncrease in mucin-secreting globlet cells in the surface epithelium of smaller bronchi and bronchioles.Irritants cause inflammation with infiltration of CD8+ T cells, macrophages, and neutrophils.No eosinophils unless patient has asthmatic bronchitis

Front 91

What is the morphological basis of airflow obstruction in chronic bronchitis?

Back 91

Small airway disease - induced by globlet cell metaplasia with mucus plugging the bronchiolar lumen, inflammation, and bronchiolar wall fibrosisCoexistent emphysema

Front 92

What is the clinical course of chronic bronchitis?

Back 92

A prominent cough with indefinite production of sputumCOPD with outflow obstructionHypercapnia, hypoxia, cyanosisEventually may be complicated by pulmonary hypertension and cardiac failure, along with recurrent infections and respiratory failure

Front 93

What is Asthma?

Back 93

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.

Front 94

What triad is associated with asthma?

Back 94

Intermittent and reversible airway obstructionChronic bronchial inflammation with eosinophilsBronchial smooth muscle cell hypertrophy and hyperreactivity

Front 95

What is the difference between extrinsic/atopic asthma and instrinsic/non-atopic asthma?

Back 95

Extrinsic/atopic asthma - 70% of cases - due to IgE and TH2 mediated immune responses to environmental antigensIntrinsic/non-atopic asthma - 30% of patients - triggered by non-immune stimuli such as aspirin; pulmonary infections, especially those caused by viruses; cold; psychological stress; exercise; and inhaled irritants.

Front 96

What are the major etiological factors for asthma?

Back 96

Genetic predisposition to type I hypersensitivity Acute and chronic airway inflammationBronchial hyper-responsiveness to a variety of stimuli

Front 97

Which interleukein released by TH2 is responsible for stimulating IgE production? For activating eosinophils? For stimulating mucus production?

Back 97

IL-4 - stimulates IgE productionIL-5 - activates eosinophilsIL-13 - stimulates mucus production

Front 98

What kind of airway remodeling changes occur in asthma?

Back 98

Hypertrophy of bronchial smooth muscleDeposition of subepithelial collagen

Front 99

What are some characteristics of the clinical picture of atopic asthma?

Back 99

Patient usually has a positive family historyAsthmatic attacks often preceded by allergic rhinitis, urticaria, eczemaTriggered by environmental antigens

Front 100

What inflammatory mediators have been implicated in the acute-phase response in asthma?

Back 100

Leukotrienes C4, D4, E - cause prolonged bronchoconstriction, increase vascular permeability, increase mucin secretionAcetylcholine - released from intrapulmonary motor nerves, causing airway smooth muscle constriction by direct stimulation of muscarinic receptorsHistamine - bronchospasm, increased vascular permeabilityProstaglandin D2 - bronchoconstriction and dilatationPlatelet-activating factor - aggregation of platelets and release of histamine from their granules

Front 101

What is the late-phase reaction in asthma?

Back 101

It may start 4-8 hours after the initial reaction and persist for 12-24 hours or more. Eosinophils are key in the late phase

Front 102

How do eosinophils play a role in asthma?

Back 102

They contain major basic protein and eosinophil cationic protein, which is directly toxic to airway epithelial cells. Eosinophil peroxidase causes tissue damage through oxidative stressOverall - they amplify and sustain the inflammatory response without additional exposure to the triggering antigen.

Front 103

Describe non-atopic asthma.

Back 103

The mechanism is not particularly clear - possibly caused by viral infections of the respiratory tract and inhaled air pollutants.Increases airway hyper-reactivity in both normal and asthmatic subjects. Virus-induced inflammation of the respiratory mucosa may lower the threshold of the subepithelial vagal receptors to irritants.

Front 104

What is drug-induced asthma?

Back 104

Some pharmacological agents induce asthma - aspirin is the most common. They present with recurrent rhinitis and nasal polyps, urticaria, and bronchospasm.

Front 105

What is occupational asthma?

Back 105

This form is stimulated by fumes, organic and chemical dusts, gases, and other chemicals in a person's work environment.

Front 106

What are Curschmann spirals?

Back 106

Whorls of shed epithelium found within mucus plugs

Front 107

What are Charcot-Leyden crystals?

Back 107

Collections of crystalloids made up of eosinophil proteins

Front 108

What is the clinical progression of asthma?

Back 108

An attack of asthma includes severe dyspnea, wheezing - expiration is the most challengingProgressive hyperinflation of the lungs with air trapped distal to the bronchi, which are constricted and filled with mucus and debrisAttacks last from 1 to several hours then subsideSome attacks may occur that does not respond to therapy and persists for days or weeks (status asthmaticum)Hypercapnia, acidosis and severe hypoxia may be fatal

Front 109

What is bronchiectasis?

Back 109

Permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic supporting tissue, resulting from or associated with chronic necrotizing infections.

Front 110

Is bronchiectasis a primary or secondary disease?

Back 110

Secondary to persisting infection or obstruction caused by a variety of conditions

Front 111

What are the characteristic symptoms of bronchiectasis?

Back 111

Cough and expectoration of copious amounts of purulent sputum

Front 112

What conditions most commonly predispose a person to bronchiectasis?

Back 112

Bronchial obstructionCongenital or hereditary conditions (cystic fibrosis, immunodeficiency, Kartagener syndrome)Necrotizing/suppurative pneumonia

Front 113

What are the two processes that contribute to the pathogenesis of bronchiectasis? How do they contribute?

Back 113

ObstructionChronic persistent infectionNormal clearance of organisms is hampered by obstruction, resulting in secondary infectionOr... chronic infection causes weakening of bronchial walls, leading to weakening and dilation.

Front 114

Describe the morphology of bronchiectasis?

Back 114

Airways are dilated, maybe 4x their normal diameterInflammatory exudate within the walls of the bronchi and bronchiolesDesquamation of lining epithelium causes areas of ulcerationMixed flora may be culturedMay be fibrosis due to extent of damage

Front 115

What may develop in chronic cases of bronchiectasis?

Back 115

Peribronchiolar fibrosisLung abscess from necrosis of the bronchial or bronchiolar walls

Front 116

What is the clinical course of bronchiectasis?

Back 116

Severe, persistent cough with expectoration of mucopurulent, sometimes fetid, sputumFlecks of blood or frank hemoptysis may occurSymptoms are episodic, precipitated by URTIs or new pathogensClubbing of the fingers may developSignificant obstructive ventilatory defects develop - hypoxemia, hypercapnia, pulmonary HTN, rarely cor pulmonaleMetastatic brain abscesses and reactive amyloidosis are uncommon complications

Front 117

What characterizes diffuse interstitial (restrictive, infiltrative) lung diseases?

Back 117

Characterized by diffuse and usually chronic involvement of the pulmonary connective tissue, principally the most peripheral and delicate interstitium in the alveolar walls.

Front 118

What is the hallmark of diffuse interstitial (restrictive, infiltrative) lung diseases?

Back 118

Reduced compliance

Front 119

Describe the pathogenesis of restrictive, infiltrative lung diseases?

Back 119

Earliest manifestation is alveolitis - accumulation of inflammatory and immune effector cells within the alveolar walls and spacesPersistence results in cellular interactions involving lymphocytes, macrophages, and neutrophils which lead to parenchymal injury, proliferation of fibroblasts, and progressive interstitial fibrosis.Activation of pulmonary macrophages is a key event in the pathogenesis of interstitial fibrosis

Front 120

What factors are secreted by alveolar macrophages in interstitial lung disease that contribute to pathogenesis?

Back 120

They secrete a host of "fibrogenic" factors - including fibroblast growth factor, transforming growth factor beta, and platelet-derived growth factor, which can attract fibroblasts as well as stimulate their proliferation. Type I pneumocytes are destroyed and type II pneumocytes proliferate.

Front 121

Describe idiopathic pulmonary fibrosis (IPF)

Back 121

Also known as cryptogenic fibrosing alveolitis - refers to a pulmonary disorder of unknown etiology characterized by diffuse interstitial fibrosis - most severe cases result in severe hypoxemia and cyanosis.

Front 122

What patient demographic is most often affected by idiopathic pulmonary fibrosis?

Back 122

Males more often than females2/3 are over 60 years old at presentation

Front 123

What is the histological pattern for IPF?

Back 123

UIP - usual interstitial pneumoniaThis is required for diagnosis of IPFHallmark - patchy, interstitial fibrosis which varies in intensityEarliest lesions contain exuberant fibroblastic proliferation, and appear as fibroblastic foci.Temporal heterogeneity - early and late lesionsHoneycomb fibrosis - alveolar collapse and formation of cystic spaces lined by hyperplastic type II pneumocytes or bronchiolar epitheliumPatchy interstitial inflammation - mostly alveolar septal infiltrate and lymphocytes with occasional plasma cells, mast cells, eosinophilsSome secondary pulmonary hypertensive changes

Front 124

What are gross features of lungs with IPF?

Back 124

Cobblestone appearance of the pleural surfaces, because of retraction of scars along the interlobular septaCut surface - shows fibrosis (firm, rubbery white areas) with lower lobe predominance and a distinctive distribution in the subpleural regions along the interlobular septa.Honeycomb fibrosis - alveolar collapse and formation of cystic spaces lined by hyperplastic type II pneumocytes or bronchiolar epithelium

Front 125

How does IPF progress clinically?

Back 125

Presents insidiouslyGradual onset of a nonproductive cough and progressive dyspnea"dry" or "Velcro"-like crackles during inspirationCyanosis, cor pulmonale, peripheral edema may develop in the later stagesMean survival is 3 years or less after diagnosis

Front 126

What is the gold standard for diagnosing IPF?

Back 126

Surgical lung biopsy - used to diagnose IPF and exclude other causes of pulmonary fibrosis

Front 127

What is nonspecific interstitial pneumonia?

Back 127

A diffuse interstitial lung disease of unknown etiology - biopsies fail to show diagnostic features of other well-characterized interstitial diseases"Wastebasket" type of diagnosis - must differentiate between this and UIP

Front 128

What are the histological signs of non-specific interstitial pneumonia?

Back 128

Two patterns - cellular and fibrosingCellular pattern - composed of mild-moderate chronic interstitial inflammation (lymphocytes, few plasma cells) in a uniform or patchy distributionFibrosing pattern - diffuse or patchy interstitial fibrosis, without the temporal heterogeneity of UIP. Fibroblastic foci are absent.

Front 129

How does a patient present with non-specific interstitial pneumonia?

Back 129

Patient presents with dyspnea and cough of several months' durationPatients with the cellular pattern have a better outcome than those with fibrosing pattern or UIP

Front 130

What is cryptogenic organizing pneumonia?

Back 130

Synonymous with "bronchiolitis obliterans organizing pneumonia"Patient presents with cough and dyspnea, radiographs show subpleural or peribronchial patchy areas of airspace consolidation.

Front 131

What are the histological signs of cryptogenic organizing pneumonia?

Back 131

Characterized by the presence of polypoid plugs of loose organizing connective tissue within alveolar ducts, alveoli and often bronchioles. Connective tissue is all the same age and the underlying lung architecture is normal.

Front 132

What is the clinical course of cryptogenic organizing pneumonia? Treatments?

Back 132

Some individuals recover spontaneously but most require treatment with oral steroids for 6 months or longer

Front 133

What is pneumoconiosis?

Back 133

A term originally coined to describe the non-neoplastic lung reaction to inhalation of mineral dusts - broadened now to include diseases induced by organic as well as inorganic particulates and some also regard chemical fume and vapor-induced non-neoplastic lung diseases as pneumoconioses.

Front 134

What are the three most common mineral dust pneumoconioses?

Back 134

Simple and complicated coal workers' pneumoconiosis - Coal dustSilicosis - silicaAsbestosis - asbestos

Front 135

What is more dangerous in a mineral dust pneumoconiosis - large particles or small particles?

Back 135

Particles between 1 and 5 micrometers are most dangerous because they get lodged at the bifurcation of the distal airwaysAny larger and they can be dislodged or removedAny smaller and they pass in and out of the alveoli, often without substantial deposition and injury

Front 136

How do inhaled particles produce pneumoconioses?

Back 136

The pulmonary alveolar macrophage is a key cellular element in the initiation and perpetuation of lung injury and fibrosis - the more reactive particles trigger the macrophages to release a number of products that mediate an inflammatory response and initiate fibroblast proliferation and collagen deposition. Some particles may reach lymphatics by drainage or marcophages, and initiate immune response leading to amplification and extension of local reactionTobacco makes it all worse

Front 137

What is simple coal workers' pneumoconiosis?

Back 137

Accumulations of macrophages in reaction to coal dust in the lungs occur with little to no pulmonary dysfunction< 10% of cases may progress to PMF/complicated CWP

Front 138

What is complicated coal workers' pneumoconiosis?

Back 138

Also known as progressive massive fibrosisFibrosis is extensive and lung function is compromised

Front 139

What is the clinical course of CWP?

Back 139

Usually a benign disease that produces little decrement in lung function

Front 140

What is the clinical course of CWP progressed to PMF?

Back 140

Increasing pulmonary dysfunctionPulmonary hypertensionCor pulmonaleTendency to progress even in the absence of further exposure

Front 141

Describe silicosis.

Back 141

Currently the most prevalent chronic occupational disease in the world - caused by inhalation of crystalline silica - mostly in occupational settings.After inhalation, the particles are ingested by macrophages, and cause activation and release of mediators by pulmonary macrophages, including IL-1, TNF, fibronectin, lipid mediators, oxygen-derived free radicals, and fibrogenic cytokines.

Front 142

What is the morphology of silicosis?

Back 142

There are silicotic nodules - characterized grossly in their early stages by tiny, barely palpable, discrete, pale-to-blackened (if there's coal) nodules in the upper zones of the lungs. Microscopically - nodules demonstrate concentrically arranged hyalinized collagen fibers surrounding an amorphous center.Distinctive "whorled" appearance of the collagen fibersPolarized microscopy reveals weakly birefringent silica particles, mostly at the center of the nodules.

Front 143

What is the clinical course of silicosis?

Back 143

Usually detected in the routine CXRs of asymptomatic workersCXR: show fine nodularity in the upper zones of the lung but PFTs normal or moderately affectedMay progress to PMF if not detected early enough

Front 144

What upper respiratory problems are linked to asbestos exposure?

Back 144

Parenchymal interstitial fibrosis (asbestosis)Localized fibrous plaques or, rarely, diffuse fibrosis in the pleuraPleural effusionsBronchogenic carcinomaMalignant pleural and peritoneal mesotheliomasLaryngeal carcinoma

Front 145

Describe the different forms of asbestos and which is more hazardous.

Back 145

Two distinct forms of asbestos - serpentine (curly flexible fiber) and amphibole (straight, stiff, brittle fiber)Amphiboles are more pathogenic than the serpentine chrysotile. The serpentine ones are more likely to become impacted in the upper respiratory passages and removed by the mucociliary elevator, or if they get stuck they are leached from tissues because they are more soluble than amphiboles.Amphiboles align themselves in the airstream and are delivered deeper into the lungs, where they may penetrate epithelial cells and reach the interstitium.

Front 146

Describe the morphology seen in asbestosis.

Back 146

Diffuse pulmonary interstitial fibrosisAsbestos bodies - golden brown, fusiform or beaded rods with a translucent center - consist of asbestos fibers coated with an iron-containing proteinaceous material - arise when macrophages attempt to phagocytose asbestos fibers. Iron derived from phagocyte ferritin. Starts in the lower lobes and subpleurally but middle an upper lobes become affected laterEnlarged airspaces from fibrous tissue contracting, forming honeycombed lungsPleural plaques - most common manifestation of asbestos exposure and are well-circumscribed plaques of dense collagen, often containing calcium. Most often on the anterior and posterolateral aspects of the parietal pleura and over the domes of the diaphragm.

Front 147

What is the clinical course of asbestosis?

Back 147

Clinically indistinguishable from other diffuse interstitial lung diseases. Progressively worsening dyspnea 10-20 years after exposure. Accompanied with productive coughDisease may remain static or progress to CHF, cor pulmonale, deathPleural plaques usually asymptomatic and are detected on radiographs as circumscribed densitiesBronchogenic carcinomas and malignant mesotheliomas develop in workers exposed to asbestos

Front 148

What cancers are far more common in asbestosis than the general population?

Back 148

Bronchogenic carcinoma 5-fold increaseMesothelioma 1000-fold increase

Front 149

What is sarcoidosis?

Back 149

A multisystem disease of unknown etiology characterized by noncaseating granulomas in many tissues and organs.

Front 150

How is sarcoidosis diagnosed?

Back 150

It is a diagnosis of exclusion, so other diseases including mycobacterial or fungal infections and berylliosis must be ruled out first.

Front 151

What is a major presenting characteristic in addition to multisystemic granulomas?

Back 151

Bilateral hilar lymphadenopathy or lung involvement (or both) - visible on CXR

Front 152

What demographic tends to get sarcoidosis?

Back 152

Adults younger than 40 years oldHigh incidence in Danish and Swedish populations and US African Americans (10x greater than US Caucasians)Supposedly more common in nonsmokers than smokers

Front 153

What are some immunologic abnormalities associated with sarcoidosis?

Back 153

Intra-alveolar and interstitial accumulation of CD4+ TH1 cellsOligoclonal expansion of T-cell subsets as determined by analysis of T-cell receptor rearrangementIncreases in T cell-derived TH1 cytokines such as IL-2 and IFN-gamma, resulting in T-cell expansion and macrophage activation respectivelyIncreases in several cytokines in the local environment (IL-8, TNF, macrophage inflammatory protein 1 alpha) favor recruitment of additional T cells and monocytes and contribute to the formation of granulomasAnergy to PPD and Candida that may result from pulmonary recruitment of CD4+ T cells and consequent peripheral depletionPolyclonal hypergammaglobulinemia, another manifestation of TH-cell dysregulationGenetic influences in individuals with sarcoidosis are suggested by familial and racial clusterings of cases and association with certain HLA genotypes

Front 154

What is a Schaumann body?

Back 154

Laminated concretions composed of calcium and proteins - sometimes seen in sarcoidosis granulomas

Front 155

What are asteroid bodies?

Back 155

Stellate inclusions enclosed within giant cells - may be present in sarcoidosis

Front 156

What may be encountered in a patient with sarcoidosis?

Back 156

Hilar and paratracheal lymph nodes enlargedSkin lesions - erythema nodosumLupus pernioInvolvement of the eye and lacrimal glandsNoncaseating epithelioid granulomas - diffuse over the body - discrete, compact collection of epithelioid cells rimmed by an outer zone of largely CD4+ T cells, with macrophages and eosinophilic cytoplasm and vesicular nuclei, may see multinucleated giant cellsLung involvementBone marrow involvementSpleen and liver may contain granulomas

Front 157

What is the clinical course for sarcoidosis?

Back 157

Usually asymptomatic and discovered as bilateral hilar adenopathy or an accidental finding at autopsy.Some symptoms: peripheral lymphadenopathy, cutaneous lesions, eye involvement, splenomegaly, hepatomegalyGradual appearance of respiratory symptoms, constitutional S/SPresence of noncaseating granulomas in a lung or lymph node biopsy suggests sarcoidosis - other identifiable causes must be excluded first

Front 158

What percentage of people with sarcoidosis go into remission with minimal or no residual manifestations?How many develop permanent lung or visual problems?Other problems?

Back 158

65-70% recover with minimal or no residual manifestations20% develop permanent lung dysfunction or visual impairment10-15% succumb to progressive pulmonary fibrosis and cor pulmonale

Front 159

What is hypersensitivity pneumonitis?

Back 159

An immunologically mediated inflammatory lung disease that primarily affects the alveoli and is therefore often called allergic alveolitis

Front 160

How does hypersensitivity pneumonitis present?

Back 160

Predominantly restrictive lung diseaseDecreased diffusion capacity, lung compliance, total lung volumeOccupational exposures are diverse, syndromes share common clinical pathologic findings and probably have very similar pathophysiology

Front 161

What is the morphology of hypersensitivity pneumonitis?

Back 161

Patchy mononuclear cell infiltrates in the pulmonary interstitiumPeribronchiolar accentuationLymphocytes, some plasma cells and epithelioid cells are presentVariable numbers of neutrophilsInterstitial noncaseating granulomas are present in 2/3+ of cases - usually in peribronchiolar locationIn advanced cases, diffuse interstitial fibrosis occurs

Front 162

What is the clinical course of hypersensitivity pneumonitis?

Back 162

It may present as an acute reaction with fever, cough, dyspnea, constitutional complaints 4-8 hours after exposureChronic disease - insidious onset of cough, dyspnea, malaise, weight loss - diagnosis of acute form usually obvious from temporal relationship of symptoms to exposure to the incriminating antigenIf antigenic exposure is terminated after acute attacks there is complete resolution within daysFailure to remove eventually results in a chronic interstitial pulmonary disease without the acute exacerbations seen on antigen re-exposure

Front 163

What is pulmonary eosinophilia?

Back 163

A group of clinical and pathologic pulmonary entities characterized by an infiltration and activation of eosinophils, the latter by elevated levels of alveolar IL-5.

Front 164

What are the categories of pulmonary eosinophilia?

Back 164

Acute eosinophilic pneumonia with respiratory failureSimple pulmonary eosinophilia (Loffler syndrome)Tropical eosinophiliaSecondary eosinophiliaIdiopathic chronic eosinophilia

Front 165

What is acute eosinophilic pneumonia with respiratory failure?

Back 165

It is a pulmonary eosinophiliaCharacterized by rapid onset of fever, dyspnea, hypoxia, diffuse pulmonary infiltrates on CXRBronchioalveolar lavage fluid typically contains 25%+ eosinophils - prompt response to corticosteroids

Front 166

What is simple pulmonary eosinophilia (Loffler syndrome)?

Back 166

It is a pulmonary eosinophiliaCharacterized by transient pulmonary lesions, eosinophilia in the blood, and a benign clinical course. The alveolar septa are thickened by an infiltrate containing eosinophils and occasional giant cells

Front 167

What is tropical eosinophilia?

Back 167

A pulmonary eosinophiliaCaused by infection with microfilariae, a parasite

Front 168

What is secondary eosinophilia?

Back 168

A pulmonary eosinophiliaSeen in association with asthma, drug allergies, certain forms of vasculitis, etc.

Front 169

What is idiopathic chronic eosinophilic pneumonia?

Back 169

A pulmonary eosinophiliaCharacterized by aggregates of lymphocytes and eosinophils within the septal walls and the alveolar spaces - typically in the periphery of the lung fields, and accompanied by high fever, night sweats and dyspneaThis is a disease of exclusion, once other causes of pulmonary eosinophilia are ruled out.

Front 170

What are some smoking-related interstitial diseases?

Back 170

Desquamative interstitial pneumonia (DIP)EmphysemaRespiratory bronchiolitisChronic bronchitisAccumulation of large numbers of macrophages with abundant cytoplasm containing dusty brown pigment - smoker's macrophages - in the airspace.

Front 171

Describe the general morphology of pulmonary infarcts.

Back 171

Wedge shaped, with base at the pleural surface and apex pointing toward the hilus of the lungRaised, red-blue areas in the early stages. Adjacent surface usually covered by a fibrinous exudate.Occluded vessel usually near the apex of the infarcted areas - red cells lyse within 48 hours and infarct pales, eventually becoming red-brown as hemosiderin is produced. Fibrous replacement begins at the margins as a gray-white peripheral zone and eventually converts the infarct into a scar that is contracted below the level of the lung substance.

Front 172

What is the hallmark of a fresh pulmonary infarct?

Back 172

Coagulative necrosis of the lung parenchyma in the area of hemorrhage

Front 173

What are the odds a patient with one pulmonary embolism will develop a second one?

Back 173

30% chance

Front 174

What are some prophylactic therapies for patients with risk of pulmonary embolism?

Back 174

Early ambulation for postoperative and postpartum patientsElastic stockingsIntermittent pneumatic compression and isometric leg exercises for bedridden patientsAnti-coagulation

Front 175

What are some nonthrombotic forms of pulmonary embolism?

Back 175

Foreign body embolism - associated with IV drug abuse (talc causing granulomatous response, etc.)Bone marrow embolism - presence of hematopoietic and fat elements within pulmonary circulation - after massive trauma and in patients with bone infarction secondary to sickle cell anemiaAmniotic fluid embolismAir embolism

Front 176

What is the proportional strength of pulmonary blood pressure to systemic blood pressure?

Back 176

Pulmonary blood pressure is 1/8 that of systemic blood pressure

Front 177

What is the technical definition of pulmonary hypertension?

Back 177

When pulmonary pressures reach 1/4 or more of systemic pressure levels.

Front 178

What are some causes for pulmonary hypertension?

Back 178

Chronic obstructive or interstitial lung diseaseRecurrent pulmonary emboliAntecedent heart disease (mitral stenosis, congenital left-to-right shunts)

Front 179

How does chronic obstructive or interstitial lung disease cause pulmonary hypertension?

Back 179

There is destruction of lung parenchyma and consequent reduction in alveolar capillaries - causing increased pulmonary arterial resistance and secondarily, elevated arterial pressure.

Front 180

How do recurrent pulmonary emboli lead to pulmonary hypertension?

Back 180

Reduction in the functional cross-sectional area of the pulmonary vascular bed, in turn, leads to increased vascular resistance

Front 181

How does antecedent heart disease like mitral stenosis and congenital left-to-right shunting lead to increased pulmonary hypertension?

Back 181

These increase left atrial pressure, leading to higher pulmonary venous pressures and ultimately pulmonary arterial hypertension.

Front 182

What is primary, or idiopathic, pulmonary hypertension?

Back 182

Pulmonary hypertension that occurs even without any known causes of increased pulmonary pressure are excluded. Most are sporadic and only 6% have the familial form with an autosomal dominant form of inheritance.

Front 183

What is the probable underlying basis for most forms of pulmonary hypertension?

Back 183

Pulmonary endothelial cell and/or vascular smooth muscle dysfunction

Front 184

Describe the pathogenesis of secondary pulmonary hypertension.

Back 184

An underlying disorder results in endothelial cell dysfunction, which reduces production of vasodilatory agents like NO and prostacyclin, while increasing synthesis of vasoconstrictive mediators like endothelin. Also production of growth factors and cytokines that induce the migration and replication of vascular smooth muscle and elaboration of the ECM.

Front 185

Describe the pathogenesis of primary pulmonary hypertension

Back 185

Particularly in the familial form, TGF-b signaling pathway has emerged as a key mediator of endothelial and smooth muscle dysfunction. Specifically bone morphogenetic protein receptor type 2 (BMPR2) - which binds to TGF-b pathway ligands. Mutations of BMPR2 have been found in 50% of familial casesLoss of function of BMPR2 leads to abnormal vascular endothelial and pulmonary smooth muscle proliferation.

Front 186

What is the BMPR2 gene and how does it relate to pulmonary hypertension?

Back 186

Mutations that cause loss of function of bone morphogenetic protein receptor type 2 are found in 50% of familial cases of primary pulmonary hypertensionResults in abnormal (usually monoclonal) vascular endothelial and smooth muscle proliferation. The gene may have limited penetrance, as not all people with the defect develop pulmonary hypertension.

Front 187

What is the role of serotonin transporter gene 5-HTT in primary pulmonary hypertension?

Back 187

Pulmonary smooth muscle cells and some individuals with primary pulmonary hypertension demonstrate increased proliferation on exposure to serotonin or serum. Genetic polymorphisms of 5-HTT may lead to enhanced expression of the transporter protein on vascular smooth muscle and are postulated to cause their proliferation.Aberrant 5-HTT function may also be the basis for pulmonary hypertension arising in persons taking the anti-obesity drug fenfluramine and its derivatives.

Front 188

What vascular alterations are seen in pulmonary hypertension?

Back 188

Atheromas in main elastic arteriesProliferation of myointimal cells and SM cells causing thickening of the intima and media with narrowing of the lumen in medium-sized muscular arteriesThickening, medial hypertrophy, and reduplication of the internal and external elastic membranes of smaller arteries and arterioles.

Front 189

What is plexogenic pulmonary arteriopathy?

Back 189

Individuals with long standing, severe primary pulmonary hypertension may develop this, in which a tuft of capillary formations is present, producing a network, or web, that spans the lumens of dilated thin-walled, small arteries.

Front 190

Describe the clinical course of secondary pulmonary hypertension.

Back 190

Develops at any age, usually reflects the underlying disease (pulmonary or cardiac) with accentuation of respiratory insufficiency and right-sided heart strain.

Front 191

Describe the clinical course of primary pulmonary hypertension.

Back 191

Almost always encountered in young persons, more often women, and marked by fatigue, syncope (particularly with exercise), dyspnea on exertion, and sometimes chest pain.They eventually develop severe respiratory insufficiency and cyanosis, and death from right-sided heart failure (decompensated cor pulmonale) within 2-5 years of diagnosis.

Front 192

What treatment is available for primary pulmonary hypertension?

Back 192

Respiratory distress can be eased by vasodilators and antithrombotic agentsLung transplant the only hope for a better prognosis

Front 193

What is the triad associated with diffuse alveolar hemorrhage syndromes?

Back 193

HemoptysisAnemiaDiffuse pulmonary infiltrates

Front 194

What is Goodpasture syndrome?

Back 194

Prototype disorder of diffuse alveolar hemorrhage syndromes. Uncommon. Characterized by proliferative, usually rapidly progressing glomerulonephritis and hemorrhagic interstitial pneumonitis. The lesions are caused by antibodies targeting non-collagenous domain of the alpha-3 chain of collagen IV. Detected in more than 90% of patients with Goodpasture syndrome.

Front 195

Describe the morphology of a classic case of diffuse alveolar hemorrhage.

Back 195

Lungs are heavy, with areas of red-brown consolidation. Microscopic - focal necrosis of alveolar walls associated with intra-alveolar hemorrhages, fibrous thickening of the septa, and hypertrophy of septal lining cells.Hemosiderin is seen a few days after an acute presentation.Linear pattern of immunoglobulin deposition is the sine qua non of diagnosis in renal biopsy specimens - also seen along the alveolar septa.

Front 196

What are some treatments for Goodpasture syndrome?

Back 196

Plasmapheresis and immunosuppressive therapy have improved the prognosisPlasma exchange removes offending antibodies, while immunosuppression inhibits antibody production.With severe renal disease, renal transplantation is eventually required.

Front 197

What is Idiopathic pulmonary hemosiderosis?

Back 197

Uncertain etiologyPulmonary manifestations and histology are similar to Goodpasture syndrome, but no associated renal disease or circulating anti-basement membrane antibody.

Front 198

How does idiopathic pulmonary hemosiderosis progress clinically?

Back 198

The disease is mild-moderate with periods of activity followed by prolonged, spontaneous remissions - most cases occur in children.

Front 199

What is Pulmonary Angiitis and Granulomatosis also known as Wegener Granulomatosis?

Back 199

Wegener granulomatosis is the prototype of the group of vasculitidis known as pulmonary angiitis and granulomatosis80% develop upper respiratory or pulmonary manifestations - lesions are characterized by a combination of necrotizing vasculitis (angiitis) and parenchymal necrotizing granulomatous inflammation.Pulmonary vessels show necrotizing granulomas, often acute and chronic inflammation are intermingled with fibrinoid necrosis.

Front 200

How does Wegener Granulomatosis manifest?

Back 200

Upper respiratory symptoms (chronic sinusitis, epistaxis, nasal perforation), pulmonary symptoms (cough, hemoptysis, chest pain).

Front 201

What are some radiological characteristics of Wegeners Granulomatosis?

Back 201

Multiple nodular densities - represent confluence of the necrotizing granulomas, some undergo cavitation

Front 202

Why are pulmonary infections so prevalent?

Back 202

1. Epithelial surfaces of the lung are constantly exposed to liters of variously contaminated air2. Nasopharyngeal flora re regularly aspirated during sleep, even by healthy persons3. Other common lung diseases render the lung parenchyma vulnerable to virulent organisms

Front 203

What is pneumonia?

Back 203

Can be broadly defined as any infection in the lungMay present as acute, fulminant clinical disease or as chronic disease with a more protracted course.

Front 204

What is bronchopneumonia vs lobar pneumonia?

Back 204

Bronchopneumonia implies a patchy distribution of inflammation that generally involves more than one lobe.Lobar pneumonia - the contiguous airspaces of part or all of a lobe are homogenously filled with an exudate that can be visualized on radiographs as a lobar or segmental consolidation.

Front 205

What organism is responsible for 90% of lobar pneumonias?

Back 205

Streptococcus pneumoniae.

Front 206

What is the best way to classify pneumonias?

Back 206

Classify by their specific etiological agent or, if no pathogen can be isolated, by the clinical setting in which infection occurs.

Front 207

Describe the onset of community acquired acute pneumonias and their causative organisms.

Back 207

The most common cause of community-acquired acute pneumonia is bacterial, typically following a viral URTIOnset: abrupt, high fever, shaking chills, pleuritic chest pain, productive mucopurulent cough - occasional hemoptysis.Streptococcus pneumoniae is the most common causative organism.

Front 208

Which groups of individuals are most often infected with Streptococcus pneumoniae?

Back 208

Those with underlying chronic diseases like CHF, COPD, diabetesThose with congenital or acquired immunoglobulin defectsThose with decreased or absent splenic function

Front 209

What is the morphology of a Streptococcal pneumoniae infection causing pneumonia?

Back 209

MOst often the lower lobes or the right middle lobe are involvedWithout antibiotics, it would progress from congestion, to red hepatization, then gray hepatization, then resolution.

Front 210

Describe each of the four stages of Streptococcus pneumoniae infection.

Back 210

Congestion - affected lobe(s) are heavy, red, boggy - histology reveals vascular congestion, proteinaceous fluid, scattered neutrophils, bacteria in the alveoli.Red heparinization - the lobe has a liver-like consistency, alveolar spaces are packed with neutrophils, red cells, and fibrinGray hepatization - llung is dry, gray, and firm because the red cells are lysed, while the fibrinosuppurative exudate persists within the alveoliResolution - in uncomplicated cases, exudates within the alveoli are enzymatically digested to produce granular, semilfluid debris that is resorbed, ingested by macrophages, coughed up, or organized by fibroblasts growing into it.

Front 211

Describe the bronchopneumatic pattern of pneumonia (streptococcus)

Back 211

There are foci of inflammatory consolidation in patches throughout one or several lobes, most often bilateral and basal.Well-developed lesions up to 3-4 cm in diameter are slightly elevated and are gray-red to yellow. Confluence may occur and produce the appearance of a lobar consolidation. Surrounding tissue usually hyperemic and edematous.

Front 212

What are some complications of Streptococcus pneumoniae pneumona?

Back 212

Tissue destruction and necrosis = abscess formationSuppurative material may accumulate in the pleural cavity, producing an empyemaOrganization of the intra-alveolar exudate may convert areas of the lung into solid fibrous tissueBacterial dissemination - meningitis, arthritis, infective endocarditis - more likely with serotype 3 pneumococci

Front 213

What are six pathogens implicated in community acquired acute pneumonias besides Streptococcus pneumoniae?

Back 213

Haemophilus influenzaeMoraxella catarrhalisStaphylococcus aureusKlebsiella pneumoniaePseudomonas aeruginosaLegionella pneumophila

Front 214

Describe Haemophilus influenzae and its role in community acquired acute pnuemonia.

Back 214

Encapsulated and unencapsulated cause CAAP - encapsulated is dangerous in children.Adults at risk include those with chronic pulmonary diseases. H. influenzae is the most common bacterial cause of acute exacerbation of COPD.Encapsulated H. influenzae type b was formerly an important cause of epiglottitis and suppurative meningitis in children but vaccination reduces the risk.One of the three organisms that causes most cases of otitis media.

Front 215

What is the most common bacterial cause of acute exacerbation of COPD? Second most common?

Back 215

Haemophilus influenzaeSecond: Moraxella catarrhalis

Front 216

Describe Moraxella catarrhalis and its role in community acquired acute pneumonia.

Back 216

M. catarrhalis is an increasing cause of bacterial pneumonia especially in elderlySecond most common bacterial cause of acute exacerbation of COPDConstitutes one of the three most common causes of otitis media.

Front 217

Describe Staphylococcus aureus and its role in community acquired acute pneumonia.

Back 217

An important cause of secondary bacterial pneumonia in children and healthy adults after viral respiratory illnessesStaphylococcus pnuemonia is associated with high incidence of complications - including lung abscesses and empyemaStaphyloccal pneumonia occuring in association with right-sided staphylococcal endocarditis is a serious complication of IV drug abuseAlso an important cause of nosocomial pneumonia

Front 218

Describe Klebsiella pneumonia and its role in community acquired acute pneumonia.

Back 218

K. pneumoniae is the most frequent cause of gram negative bacterial pneumonia.Frequently afflicts debilitated and malnourished persons, like alcoholicsThick and gelatinous sputum is characteristic because the organism produces an abundant viscid capsular polysaccharide, which the individual may have difficulty coughing up

Front 219

What is the most common gram negative organism that causes bacterial pneumonia?

Back 219

Klebsiella pneumoniae

Front 220

Describe Pseudomonas aeruginosa and its role in community acquired acute pneumonia.

Back 220

Most commonly seen in nosocomial infectionsCommon in patients who are neutropenic, usually secondary to chemotherapy, extensive burns, those requiring mechanical ventilationPropensity to invade blood vessels at the site of infection with consequent extra-pulmonary spread; Fulminant disease, death often occurs within a matter of days.Histologically - coagulation necrosis of the pulmonary parenchyma with organisms invading the walls of necrotic blood vessels (Pseudomonas vasculitis)

Front 221

Describe Legionella pneumophila and its role in community acquired acute pneumonia.

Back 221

The agent of legionnaire disease - Pontaic fever is related, and self-limited. Flourishes in artificial aquatic environments - transmission via aerosolized organisms or aspiration of contaminated waterCommon in those with cardiac, renal, immunologic, or hematologic disease. Organ transplant recipients are particularly susceptible.May be quite severe, frequently requiring hospitalization, and immunosuppressed individuals may have fatality of 30-50%Rapid diagnosis via Legionella antigens in urine or by positive fluorescent antibody test on sputum samples - culture is gold standard for Dx.

Front 222

What is community acquired atypical pneumonia?

Back 222

Pneumonia, but atypical because of the moderate amounts of sputum, absence of physical findings of consolidation, moderate elevation of white cell count, lack of alveolar exudates.

Front 223

What organisms often cause community acquired atypical pneumonia?

Back 223

Mycoplasma pneumoniae is the most commonMostly among children and young adultsSporadic or local epidemics in closed communitiesAlso caused by viruses: infuenza type A, B; RSV; adenovirus; rhinovirus; rubeola; varicella;Chalmydia pneumoniaeCoxiella burnetti

Front 224

Describe the morphology of community acquired atypical pneumonia.

Back 224

Patchy or whole lobes bilaterally or unilaterallyMacroscopically - affected areas are red-blue, congested, subcrepitantInflammatory region is largely confined within the walls of the alveoliSepta widened and edematous, contain mononuclear infiltrates of lymphocytes, histiocytes, and occasionally plasma cells.Remarkably free of cellular exudate, but hyaline membranes may develop in full-blown diffuse alveolar damage.

Front 225

Which has a good amount of cellular exudate - bacterial pneumonia or atypical pneumonia

Back 225

Bacterial pneumonia has cellular exudate

Front 226

Describe the clinical course of community acquired atypical pneumonias.

Back 226

Extremely variedMay go undiagnosed and appear like a severe URTI or "chest cold"May present as fulminant life-threatening infection in imunocompromised patientsOnset usually acute, nonspecific febrile ilness - headache, malaise, cough, minimal sputum. Edema, exudation, may be respiratory distress seemingly out of proportion to the physical and radiographic findings.

Front 227

How do you diagnose community acquired atypical pneumonia? Treat?

Back 227

Test for Mycoplasma antigens and PCR testing for Mycoplasma DNAOften treated with Macrolides since they are effective against Mycoplasma and Chlamydia pneumoniae

Front 228

How is SARS distinct clinically from the other coronaviruses, which cause 1/3 of URTIs?

Back 228

SARS-CoV differs in that it is more able to infect the lower respiratory tract and induce viremia.

Front 229

What are the symptoms of SARS?

Back 229

Patient becomes ill 2-10 days after exposureSymptoms: fever, myalgia, headache, chills, diarrhea; Respiratory symptoms include dry cough, dyspnea

Front 230

What are some of the histological/morphological characteristics of lungs of SARS patients?

Back 230

Lungs demonstrate DAD and multinucleated giant cells

Front 231

What are nosocomial pneumonias?

Back 231

Hospital-acquired pneumoniasMore often caused by organisms in the group "Ventilator-associated pneumonia"Gram-negative rods (Enterobacteriaceae and Pseudomonas spp) and Staphylococcus aureus are the most common isolates.Streptococcus pneumoniae is NOT a major pathogen in nosocomial infections.

Front 232

What is aspiration pneumonia?

Back 232

Occurs in markedly debilitated patients or those who aspirate gastric contents either while unconscious or during repeated vomitingResulting pneumonia is partly chemical from gastric acid, and partly bacterial - aerobes are more common than anaerobes, but often is necrotizing and pursues a fulminant clinical course. Those who survive often suffer abscesses

Front 233

What is a lung abscess?

Back 233

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

Front 234

How are the organisms that cause lung abscesses introduced?

Back 234

Aspiration of infective materialAspiration of gastric contentsComplication of necrotizing bacterial pneumonias, especially Staphylococcus aureus, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas spp. Rarely type 3 pneumonocci. Mycotic infections and bronchiectasis also.Bronchial obstructionSeptic embolismHematogenous spread of bacteria in disseminated pyogenic infectionAnaerobic bacteria are present in almost all lung abscesses, sometimes in vast numbers. Exclusive isolates in 1/3-2/3 of cases.

Front 235

What are the most frequent anaerobic bacteria encountered in lung absesses?

Back 235

PrevotellaFusobacteriumBacteroidesPeptostreptococcusMicroaerophilic streptococci

Front 236

Where do pulmonary abscesses most often occur?

Back 236

Most often occur on the right side since the airway is more vertical. Most are single.Tend to occur in the posterior segment of the upper lobe and in the apical segments of the lower lobe.

Front 237

What is the clinical course of a lung abscess?

Back 237

Prominent cough that yields copious amounts of foul-smelling, purulent, sanguineous sputum - occasional hemoptysis. Fever, malaise, finger clubbing, weight loss, anemiaInfective abscesses in 10-15% of persons with bronchogenic carcinoma - so if lung abscess is in an older person must consider carcinoma. Secondary amyloidosis may develop in chronic cases.

Front 238

How are lung abscesses treated?

Back 238

Treatment includes antibiotic therapy and surgical drainage. Mortality rate ~10%

Front 239

What are the two broad groups of lung cancers?

Back 239

Small-cell lung cancer (SCLC)Non-small-cell lung cancer (NSCLC)

Front 240

What is the difference between the SCLC and NSCLC clinically and treatment-wise?

Back 240

SCLC = metastasized by the time of Dx and are not curable by surgery - MUST be treated with chemotherapy w/ or w/o radiationNSCLC = usually respond poorly to chemotherapy, better to do surgery

Front 241

What are some genetic differences between SCLC and NSCLC?

Back 241

SCLC - characterized by a high frequency of RB gene mutationsNSCLC - p16/CDKN2A gene is commonly inactivated. ALso there are activating KRAS and EGFR oncogene mutations.

Front 242

What is the sequence of genetic molecular events leading to a pulmonary carcinoma?

Back 242

Inactivation of tumor suppressor genes on chromosome 3p is an early eventp53 mutations and KRAS oncogene activation occur laterA subset of adenocarcinomas have mutations in epidermal growth factor receptor

Front 243

Statistically how many cases of lung cancer occur in smokers or those who stopped recently?

Back 243

90%

Front 244

In which are neuroendocrine markers (dense core granules, expression of chromogranin, neuron-specific enolase and synaptophysin) present - SCLC or NSCLC?

Back 244

Present in SCLCAbsent in NSCLC

Front 245

In which type, NSCLC or SCLC, is mucin present?

Back 245

Present in adenocarcinomas (NSCLC)Absent in SCLC

Front 246

What peptide hormones are produced in SCLC?

Back 246

Adrenocorticotropic hormone, antidiuretic hormone, gastrin-releasing peptide, calcitonin

Front 247

What peptide hormones are produced in NSCLC?

Back 247

Parathyroid hormone-related peptide (PTH-rp) in squamous cell carcinoma

Front 248

In what type of NSCLC are KRAS mutations present?

Back 248

Adenocarcinomas

Front 249

How do carcinomas in the lungs begin and develop?

Back 249

Start as small mucosal lesions that are firm and gray-whiteMay form intraluminal masses, invade the bronchial mucosa, form large bulky masses pushing into adjacent lung parenchymaSome masses undergo cavitation caused by central necrosis or develop focal areas of hemorrhageMay extend to the pleura, invade the pleural cavity and chest wall, and spread to adjacent intrathoracic structures. Distant spread via the lymphatics or hematogenous route

Front 250

In what gender are squamous cell carcinomas more common?

Back 250

Men > Women

Front 251

How do squamous cell carcinomas develop?

Back 251

CLosely correlated with smokingTend to arise centrally in major bronchiSpread to local hilar nodesDisseminate outside the thorax later than other typesLarge lesions may undergo central necrosis, with resulting cavitationOften preceded by years of squamous metaplasia or dysplasia in the bronchial epithelium

Front 252

What is carcinoma in situ?

Back 252

A phase during which atypical cells may be identified in cytological smears of sputum or in bronchial lavage fluids or brushings, although the lesion is asymptomatic and undetectable on radiographs.

Front 253

Are squamous cell carcinomas well differentiated or not?

Back 253

They can range from being well differentiated with keratin pearls and intercellular bridges, to poorly differentiated neoplasms having only minimal residual squamous features

Front 254

What is an adenocarcinoma and how does it start?

Back 254

They occur as central lesions but are usually more peripheral - in relation to peripheral lung scars (not caused by the scars though)Grow slowly in general, form smaller masses, but metastasize early.

Front 255

What is the most common type of lung cancer in women and nonsmokers?

Back 255

Adenocarcinoma

Front 256

Describe the histological features of an adenocarcinoma.

Back 256

Various types:They are acinar - gland formingPapillarySolidSolid variants require demonstration of intracellular mucin production by special stains to establish that it is an adenocarcinoma

Front 257

What is an atypical adenomatous hyperplasia?

Back 257

The putative precursor of peripheral adenocarcinomas - well-demarcated focus of epithelial proliferation composed of cuboidal to low-columnar cells resembling Clara cells or type 2 pneumocytes. Various cytologic atypia (nuclear hyperchromasia, pleomorphism, prominent nucleoli

Front 258

What are bronchioloalveolar carcinomas? (BAC)

Back 258

A subtype of adenocarcinomas - involve peripheral parts of the lung either as a single nodule ore as multiple diffuse nodules. May produce pneumonia-like consolidation.KEY FEATURE: Growth along preexisting structures and preservation of alveolar architecture.

Front 259

What is a key feature of bronchioloalveolar carcinoma?

Back 259

They grow along preexisting structures and preserve the alveolar architecture.

Front 260

What are BASCs?

Back 260

Bronchioalveolar stem cells

Front 261

What is the role of BASCs in neoplasm?

Back 261

Bronchioalveolar stem cells, following lung ingjury, undergo expansion, replenishing the normal cell types (Clara cells, alveolar cells) - facilitating epithelial regeneration - it is thought they incur the initiating oncogenic event so the cells escape normal check point mechanisms and result in pulmonary adenocarcinomas.

Front 262

What are large-cell carcinomas?

Back 262

Undifferentiated malignant epithelial tumors that lack the features of small-cell lung cancer and glandular or squamous differentiation

Front 263

How do small-cell lung carcinomas typically appear?

Back 263

Pale gray, centrally located masses with extension into the lung parenchyma and early involvement of the hilar and mediastinal nodes. Composed of tumor cells with a round to fusiform shape, scant cytoplasm, and finely granular chromatin.

Front 264

Which cancer, NSCLC or SCLC, most often causes paraneoplastic syndrome?

Back 264

Small cell lung carcinoma SCLC

Front 265

What kind of tumor cells show fragmentation and "crush artifact" and nuclear molding resulting from close apposition of tumor cells that have scant cytoplasm?

Back 265

Small lung cell carcinoma SCLC

Front 266

Which tumor cells originate from pulmonary neuroendocrine cells?

Back 266

SCLC Small cell lung carcinoma

Front 267

From what cell line do carcinoid (SCLC) tumors originate?

Back 267

Pulmonary neuroendocrine cells.

Front 268

What is a Pancoast tumor?

Back 268

A tumor that is destroying the first and second ribs, sometimes thoracic vertebraeThey are apical tumors that invade the brachial or cervical sympathetic plexusand cause severe pain in the distribution of the ulnar nerve or to produce Horner syndrome.

Front 269

What are the symptoms of Horner syndrome?

Back 269

Ipsilateral enophthalmos, ptosis, miosis, and anhidrosis

Front 270

What is a blank reaction?

Back 270

In the context of cancers, blank reactions is the way that cancers establish a fibroblast-made scaffolding on which to grow and spread.

Front 271

What is chronic pneumonia?

Back 271

A localized lesion in an immunocompetent person, with or without regional lymph node involvement. Typically granulomatous inflammation - due to bacteria or fungi.

Front 272

What is the most common cause of death resulting from a single infectious agent?

Back 272

TuberculosisMycobacterium tuberculosis

Front 273

What are some disease states that increase the risk of Tuberculosis?

Back 273

Diabetes mellitusHodgkin diseaseChronic lung disease (silicosis)Chronic renal failureMalnutritionAlcoholismImmunosuppression

Front 274

What factor is the single most important risk to developing tuberculosis?

Back 274

Decrease in the capacity to maintain T cell-mediated immunity against the infectious agent.

Front 275

What diseases or infections can produce false-negatives for PPDs?

Back 275

Certain viral infectionsSarcoidosisMalnutritionHodgkin's LymphomaImmunosuppressionOverwhelming active Tuberculosis

Front 276

How does the tuberculosis bacillus behave once it enters a macrophage?

Back 276

It inhibits normal microbicidal responses by manipulation of endosomal pH and arrest of endosomal maturationImpaired phagolysosome formation, unhindered mycobacterial proliferationBacillary proliferation within the pulmonary alveolar macrophages and air spaces, with resulting bacteremia and seeding of multiple sites.

Front 277

What is NRAMP1?

Back 277

Natural resistance-associated macrophage protein 1 - a gene coding for a transmembrane ion transport protein in endosomes and lysosomes that may contribute to microbial killing.

Front 278

What is the role of IFN-gamma in the response to Tuberculosis?

Back 278

IFN-gamma is released by the CD4+ T cells of the TH1 subset, and activate macrophages. The macrophages release...TNF - recruits monocytes and activates them into epithelioid histiocytes, forming granulomatous responseExpression of the iNOS (inducible NO-synthasse) gene which elevates nitric oxide levels and helps oxidize things, and generate reactive nitrogen intermediates. ROS generation, antibacterial activity

Front 279

What is primary tuberculosis?

Back 279

Tuberculosis that develops in a previously unexposed, unsensitized individual

Front 280

What is a Ghon focus? Ghon complex?

Back 280

A 1 to 1.5cm area of gray-white inflammatory consolidation - usually undergoes caseous necrosis. Tends to occur in the upper part of the lower lobe, or the lower part of the upper lobe.Combination of parenchymal lesion and nodal involvement - Ghon complex.

Front 281

What is a Ranke complex?

Back 281

After the Ghon complex undergoes progressive fibrosis, often followed by radiologically detectable calcification, it is called a Ranke complex.

Front 282

Describe the morphological spectrum of tuberculosis granulomas/tubercles.

Back 282

Central granular caseation, surrounded by epithelioid and multinucleated giant cellsFoamy histiocytes are packed with mycobacteriaFibroblastic rim punctuated by lymphocytes

Front 283

What are the chief implications of primary tuberculosis?

Back 283

Induces hypersensitivity and increased resistanceThe foci of scarring may harbor viable bacilli for yearsDisease may develop without interruption into so-called progressive primary tuberculosis

Front 284

What are some characteristics of progressive primary tuberculosis?

Back 284

Acute bacterial pneumoniaLower, middle lobe consolidationHilar adenopathy, pleural effusionCavitation is rareComplication - lymphohematogenous dissemination - tuberculous meningitis and miliary tuberculosis

Front 285

What is secondary tuberculosis?

Back 285

Also known as reactivation or postprimary tuberculosisA pattern of disease that arises in a previously TB-sensitized hostOnly develops in about 5% of those who have primary TB

Front 286

Where does secondary tuberculosis tend to occur?

Back 286

Classically located in the apex of one or both upper lobesPossibly from high oxygen tension?

Front 287

What are some characteristics of secondary tuberculosis?

Back 287

Cavitation occurs readilyLess involvement of regional lymph nodesLocalized in apex of one or both upper lobesVery prevalent in HIV-positive patients

Front 288

Why would an immunocompetent individual have a positive sputum-smear for AFB compared to an immunocompromised individual with a higher bacterial load?

Back 288

Immunocompetent individuals with secondary TB have more tissue damage, resulting in more exposure of the bacteria to the sputumIn immunocompromised individuals, the bacteria are concealed within the cells, so fewer bacteria are in the sputum.

Front 289

Describe an initial lesion in tuberculosis.

Back 289

Usually less than 2 cm in diameter, small focus of consolidation, firm, sharply circumscribed, gray-white to yellow areas that have a variable amount of central caseation and peripheral fibrosis.May go through progressive fibrous encapsulation, leaving only fibrocalcific scars. Active lesions show characteristic coalescent tubercles with central caseation.

Front 290

How do the lesions appear in progressive pulmonary tuberculosis?

Back 290

Apical lesion enlarges with expansion of the area of caseationErosion into a bronchus evacuates the caseous center, creating a ragged, irregular cavity lined by caseous material - poorly walled off by fibrous tissueHemoptysis occurs from erosion of blood vessels

Front 291

What is miliary pulmonary disease, and what are some characteristics?

Back 291

Organisms drain through lymphatics into the lymphatic ducts and empty into the right side of the heart, entering pulmonary arteries.Individual lesions are either microscopic or small, visible foci of yellow-white consolidation scattered through the lung parenchyma (miliary = millet).May coalesce with total consolidation of large regions, entire lobes

Front 292

What are some developments associated with progressive pulmonary tuberculosis?

Back 292

Pleural effusionsTuberculosis empyemaObliterative fibrous pleuritis

Front 293

What is systemic miliary tuberculosis?

Back 293

When infective foci in the lungs seed the pulmonary venous return to the heart, the organisms subsequently disseminate through the systemic arterial system.Most prominent in the liver, bone marrow, spleen, adrenals, meninges, kidneys, fallopian tubes, and epididymis

Front 294

What is isolated-organ tuberculosis?

Back 294

May appear in any one of the organs or tissues seeded hematogenously and may be the presenting manifestation of tuberculosis. Organs involved:Meninges - tuberculous meningitisKidneys - renal tuberculosisAdrenals - formerly part of Addison diseaseBones - osteomyelitisFallopian tubes - salpingitisPott disease - vertebrae involvement

Front 295

What is the most common form of extrapulmonary tuberculosis?

Back 295

Lymphadenitis - usually in the cervical region - "scrofula"Unifocal in HIV-negative people, otherwise multifocal with systemic symptoms and pulmonary or other organ involvement by active tuberculosis.

Front 296

What is intestinal tuberculosis?

Back 296

A form of tuberculosis contracted by ingesting contaminated milk - used to be more common,but now is a complication of protracted advanced secondary tuberculosis, secondary to the swallowing of coughed-up infective material. Tends to cause mucosal lymphoid aggregates of the small and large bowel which undergo inflammatory enlargement with ulceration of the overlying mucosa

Front 297

How are tuberculosis bacilli identified?

Back 297

Conventional cultures may take up to 10 weeksSome liquid media-based radiometric assays can give an answer within 2 weeksPCR amplification is even mroe rapidSputum acid-fast stains, or use of fluorescent auramine rhodamine; Two sputum exams are required before conferring sputum negativity

Front 298

What is the gold standard for identifying M. tuberculosis in a patient?

Back 298

Cultures - because it also allows for testing of drug susceptibility

Front 299

What are some nontuberculous mycobacterial diseases/pathogens?

Back 299

M. avium-intracellulareM. kansasiiM. abscessusMay present as upper lobe cavitary disease, mimicking TB, especially in individuals with long-standing history of smoking or alcoholism.Presents as a chronic but clinically localized pulmonary disease.

Front 300

What is the effect of M. avium in HIV-positive patients?

Back 300

Presents as disseminated disease, associated with systemic symptoms (fever, night sweats, weight loss)HepatosplenomegalyLymphadenopathyGI symptoms: diarrhea, malabsorptionFoamy histiocytes "plugged" with atypical mycobacteria

Front 301

Describe H. capsulatum. What does it cause?

Back 301

HistoplasmosisEndemic in Ohio, central Mississippi River valley, along the Appalachians. Warm moist soil, enriched by bat and bird droppings provides the ideal medium for growth of the mycelial form, which produces infectious spores.

Front 302

Describe the morphology of H. capsulatum.

Back 302

Round to oval, small yeast forms measuring 2-5 micrometers in diameter.

Front 303

Describe C. immitis. What does it cause?

Back 303

CoccidioidomycosisEndemic in the Southwest and Far West of US, especially in the San Joaquin Valley, where it is known as "valley fever"

Front 304

Describe the morphology of C. immitis.

Back 304

Thick-walled, nonbudding spherules, 20-60 micrometers in diameter, often filled with small endospores.

Front 305

Describe B. dermatitidis. What does it cause?

Back 305

BlastomycosisEndemic area is confined in the US to areas overlapping with those where histoplasmosis is found.

Front 306

Describe the morphology of B. dermatitidis.

Back 306

Round to oval, larger than Histoplasma (5-25 micrometers in diameter). Reproduce by characteristic "broad based" budding

Front 307

What are the three main clinical manifestation categories for Histoplasmosis, Coccidioidomycosis, or Blastomycosis?

Back 307

Acute (primary) Pulmonary InfectionChronic (cavitary) Pulmonary DiseaseDisseminated Miliary Disease

Front 308

How does Histoplasmosis, Coccidoidomycosis, or Blastomycosis start, with primary pulmonary infection?

Back 308

There are nodules, composed of aggregates of macrophages stuffed with organisms, and associated with similar lesions in the regional lymph nodesDevelop into small granulomas with giant cells, may develop central necrosis and later fibrosis and calcification. Similarity to primary TB is striking

Front 309

How is Acute (primary) Pulmonary Infection by a dimorphic fungus differentiated from TB?

Back 309

Must identify the yeast forms - with a periodic acid-Schiff or silver stain.

Front 310

Describe the clinical presentation of Acute (primary) Pulmonary infection with a dimorphic fungus?

Back 310

Clinically resembles a "flulike" syndrome, often self limited. In a vulnerable host, chronic cavitary pulmonary disease develops, with predilection for the upper lobe.

Front 311

Describe the clinical presentation of Chronic (cavitary) Pulmonary Disease from a dimorphic fungus.

Back 311

Tends to affect the upper lobe and resembles the secondary form of TBThere may be perihilar mass lesions that resemble bronchogenic carcinoma radiologicallyCough, hemoptysis, and some dyspnea/chest pain may appear

Front 312

Describe disseminated disease caused by a dimorphic fungus.

Back 312

There are no well-formed granulomasFocal collections of phagocytes stuffed with yeast forms are seen within cells of the mononuclear phagocyte system, including in the liver, spleen, lymph nodes, lymphoid tissue of GI tract, and bone marrow. Adrenals and meninges may be involved, and in a minority of cases, ulcers form in the nose and mouth, on the tongue, or in the larynx.

Front 313

Describe the clinical presentation of disseminated disease caused by a dimorphic fungus.

Back 313

A hectic, febrile illness with hepatosplenomegaly, anemia, leukoplakia, and thrombocytopenia. Cutaneous infections with disseminated Blastomyces frequently induce striking epithelial hyperplasia, which may be mistaken for SCC

Front 314

What are some pulmonary opportunistic pathogens (bacteria, viruses, fungi)? Yes there are a gajillion, but what has Robbins mentioned?

Back 314

Bacteria: Pseudomonas aeruginosa, Mycobacterium species, Legionella pneumophila, Listeria monocytogenesViruses - Cytomegalovirus, HerpesvirusFungi - Pneumocystis jiroveci, Candida species, Aspergillus species, Cryptococcus neoformans

Front 315

What are some signs of CMV at the cellular level?

Back 315

Cytomegalovirus is a member of the herpesvirus family, may produce a variety of disease manifestationsInfected cells exhibit gigantism of entire cell and the nucleus. Enlarged inclusion with a clear halo - giving an "owl's eye" cell appearance.

Front 316

What are the different modes of transmission of CMV?

Back 316

Transplacentally --> Fetus, Congenital CMVCervical or vaginal secretions at birth, or later through breast milk - Perinatal CMVVenereal transmission in those over 15 years old - also spreads via respiratory secretions and fecal-oralIatrogenic transmission at any age

Front 317

What is CMV mononucleosis?

Back 317

In healthy young children and adults, disease is almost always asymptomatic50-100% of adults demonstrate anti-CMV antibodiesMost common manifestation in immunocompetent hosts is an infectious mono-like illness with fevver, atypical lymphocytosis, lymphadenopathy, and hepatomegaly accompanied by abnormal LFTs, suggesting mild hepatitis. Most recover without sequelae but excretion of virus may occur for months to years afterwards.Remains latent in leukocytes

Front 318

What are the common immunosuppressed groups that get clinical CMV?

Back 318

Recipients of organ transplants - heart, liver, kidney - CMV usually from the donor but reactivation may occur.Recipients of allogeneic BMTs - usually reactivation of latent CMV in the recipientPersons with AIDS - reactivation of latent infection and are also infected by their sexual partners. CMV is the most common opportunistic viral pathogen in AIDS.

Front 319

What is the most common opportunistic viral pathogen in patients with AIDS?

Back 319

CMV - Cytomegalovirus

Front 320

What organ systems are most often affected by CMV in immunosuppressed patients?

Back 320

Lungs - PneumonitisGI tract - ColitisRetina - Retinitis

Front 321

Describe the behavior of P. jiroveci in immunocompetent and immunocompromised patients.

Back 321

An opportunistic infectious agent - nearly everyone is exposed by age 5 - remains latentReactivation and clinical disease almost exclusively in immunocompromised patients. Mostly in AIDS patients and malnourished infants. Largely confined to the lungs.

Front 322

Describe the microscopic morphology of the lungs with Pneumocystis pneumonia.

Back 322

Involved areas demonstrate intra-alveolar foamy, pink-staining exudate with H&E stains ("cotton candy" exudate), and septa are thickened by edema and a minimal mononuclear infiltrate.Organism can be revealed in trophozoite or encysted form.Silver stains reveal cup-shaped cyst walls (5-8 micrometers in diameter) in the alveolar exudates. Trophozoites can be revealed with methylene blue or Giemsa stains in sputum samples of about 50% of patients.

Front 323

What is the most common clinical presentation of Pneumocystis pneumonia?

Back 323

Fever, dry cough, dyspnea (and immunocompromised state) with bilateral perihilar and basal infiltratesHypoxia, often there is a restrictive lung defect, BAL is best way to identify the organism.

Front 324

What is the most frequent disease-causing fungus?

Back 324

Candida albicans

Front 325

Describe the morphology of C. albicans.

Back 325

Yeastlike forms - blastoconidia. Pseudohyphae, and true hyphae. Pseudohyphae are an important diagnostic clue and represent budding yeast cells joined end-to-end at constrictions, simulating true fungal hyphae. Organisms may be visible with routine hematoxylin and eosin stains, but a variety of "fungal" stains (Gomori methenamine-silver, periodic acid-Schiff) are used to highlight the pathogens.

Front 326

Describe the oral pattern of infection of C. albicans.

Back 326

Most common pattern: superficial infection on mucosal surfaces of oral cavity - "thrush". Florid proliferation creates gray-white, dirty-looking pseudomembranes composed of matted organisms and inflammatory debris. Deeper there is mucosal hyperemia and inflammation.

Front 327

What groups are most at risk for oral candidiasis (thrush)?

Back 327

NewbornsDebilitated PatientsChildren receiving oral corticosteroids for asthmaAfter a course of broad-spectrum antibiotics that destroy competing floraHIV-positive patients

Front 328

Describe Candida vaginitis.

Back 328

Extremely common vaginal infection in women, especially hose who are diabetic, pregnant, or on oral contraceptive pills. Usually associated with intense itching and a thick, curdlike discharge.

Front 329

Describe Candida esophagitis.

Back 329

Common in AIDS patients and those with hematolymphoid malignanciesPresent with dysphagia, retrosternal pain. Endoscopy reveals white plaques and pseudomembranes resembling oral thrush on the esophageal mucosa.

Front 330

What is cutaneous candidiasis?

Back 330

Presents in many forms, including infection of the nail proper (onychomycosis), nail folds (paronychia), hair follicles (folliculitis), moist, intertriginous skin such as armpits or webs of the fingers and toes (intertrigo), and penile skin (balanitis). "Diaper rash" is often a cutaneous candidal infection.

Front 331

What is chronic mucocutaneous candidiasis?

Back 331

A chronic refractory disease afflicting the mucous membranes, skin, hair, and nails - it is associated with underlying T-cell defects. Associated conditions include endocrinopathies (most often hypoparathyroidism and Addison disease) and the presence of autoantibodies. Disseminated candidiasis is rare.

Front 332

What are some common patterns associated with invasive candidiasis?

Back 332

Bloodborne dissemination of organisms to various tissues or organs may occur via...Renal abscessesMyocardial abscesses and endocarditisBrain involvement (meningitis, parenchymal microabscesses)Endophthalmitis (any eye structure)Hepatic abscessesCandida pneumonia, usually with bilateral nodular infiltrates, resembling Pneumocystis pneumonia.Patients with acute leukemias who are profoundly neutropenic post-chemo are very prone to systemic disease.

Front 333

Describe Cryptococcosis and its pathogenicity.

Back 333

Caused by C. neoformans, rarely in healthy people. Almost only in immunocompromised hosts, particularly those with AIDS or hematolymphoid malignancies. Manifests as pulmonary, CNS, or disseminated disease. Most likely acquired by inhalating soil or bird droppings - localizes in the lungs and disseminates - favorite site is the meninges.

Front 334

What disease is associated with soap bubble lesions in the perivascular Virchow-Robin spaces?

Back 334

Cryptococcosis of the meninges

Front 335

What are some opportunistic molds?

Back 335

Mucormycosis and invasive aspergillosis. Always limited to immunocompromised hosts, with hematolymphoid malignancies, profound neutropenia, corticosteroid therapy, or post-allogeneic BMT

Front 336

Describe the morphology of Mucormycosis and Aspergillus species.

Back 336

Mucormycosis, caused by Zygomycetes - nonseptate hyphae that branch at right anglesRhizopus/Mucor are the two fungi that are important within the Zygomycetes class.Aspergillus - septate hyphae, branch at acute angles

Front 337

Describe the morphology of Cryptococcus.

Back 337

5-10 micrometer yeast, thick gelatinous capsule, reproduces by budding. Unlike Candida, pseudohyphal or true hyphal forms are not seen. Capsule is invaluable to diagnosis - in routine H&E stains it is not easily seen but a clear "halo" can be seen around the individual fungi representing the capsule. The capsular polysaccharide antigen is the substrate for the cryptococcal latex agglutination assay, which is positive for more than 95% of patients with the organism.

Front 338

What kind of local reaction is more characteristic of Zygomycetes and Aspergillus?

Back 338

A nondistinctive, suppurative, sometimes granulomatous reaction with a predilection for invading blood vessel walls, causing vascular necrosis and infarction

Front 339

Describe rhinocerebral and pulmonary mucormycosis.

Back 339

Zygomycetes tend to colonize the nasal cavity, sinuses, and then spread to the brain, orbit, and other structures there.Diabetics are more likely to develop rhinocerebral mucormycosis. Pulmonary disease can be localized or present radiologically with diffuse "miliary" involvement.

Front 340

Describe invasive aspergillosis.

Back 340

Almost exclusively in immunosuppressed patients. Fungus preferentially localizes to the lungs, presents as a necrotizing pneumonia. Tend to invade blood vessels, so systemic dissemination (to brain) may be a fatal complication.

Front 341

What is allergic bronchopulmonary aspergillosis?

Back 341

It occurs in patients with asthma who develop an exacerbation of symptoms caused by a type I hypersensitivity against the fungus growing in the bronchi. These patients tend to have circulating IgE antibodies against Aspergillus and peripheral eosinophilia.

Front 342

What is an Aspergilloma?

Back 342

A "fungus ball" which occurs by colonization of preexisting pulmonary cavities by the fungus May act as ball valves, occluding the cavity and thus predisposing to infection and hemoptysis

Front 343

What are some of the most commonly implicated organisms in HIV-related pulmonary infections?

Back 343

S. pneumoniaeS. aureusH. influenzaeGram-negative rods

Front 344

What are some common noninfectious diseases that may cause pulmonary infiltrates in HIV-infected individuals?

Back 344

Kaposi's sarcomaPulmonary non-Hodgkin lymphomaPrimary lung cancer

Front 345

How can CD4+ T cell count be used to narrow down a DDx for HIV-infected patients with a pulmonary infection?

Back 345

Bacterial and Tubercular infections are more likely at higher CD4 counts > 200 cells/mm3Pneumocystis pneumonia strikes below < 200 cell/mm3CMV and M. avium complex infections are uncommon until CD4 counts are < 50 cells/mm3

Front 346

What is the most common cell of origin of primary lung cancers?

Back 346

Bronchial epithelial cells - site of origin of 95% of primary lung tumors (carcinomas)5% are a miscellaneous group that includes bronchial carcinoids, mesenchymal malignancies, lymphomas, a few benign lesions.

Front 347

What is the most common benign lesion in the lungs?

Back 347

A hamartoma - discrete, small (3-4 cm), spherical, appear as "coin" or "button" lesions on chest radiographs. Consist mainly of mature cartilage but may be mixed with fat, fibrous tissue, blood vessels in varying proportions.

Front 348

What are the four major histological types of carcinomas of the lung?

Back 348

Squamous cell carcinomaAdenocarcinomaSmall-cell carcinomaLarge-cell carcinoma

Front 349

What is the most common primary tumor arising in women, lifetime nonsmokers, and persons younger than 45 years?

Back 349

Adenocarcinomas

Front 350

What are the two broad groups into which lung cancers are classified?

Back 350

Small-cell lung cancer Non-small-cell lung cancer

Front 351

What types of cancers are included in NSCLC?

Back 351

AdenocarcinomasLarge Cell CarcinomasSquamous Cell Carcinomas

Front 352

Why have carcinomas been divided into the large categories of Non-small cell and small cell?

Back 352

SCLCs have metastasized by the time of diagnosis and hence are not curable by surgery. Best treated by chemotherapy, with or without radiation.NSCLCs respond poorly to chemotherapy, and are better treated with surgery

Front 353

What are the genetic differences between SCLCs and NSCLCs?

Back 353

SCLC - high frequency of RB gene mutations. NSCLC - p16/CDKN2A are inactivated in NSCLC. KRAS and EGFR oncogene mutations are found in adenocarcinomas.

Front 354

What is EGFR and how does it relate to lung cancer?

Back 354

EGFR is epidermal growth factor receptor, and mutations in these receptors result in a subset of adenocarcinomas common in non-smoking women of the Far East. Luckily, there is a class of drugs that inhibits EGFR signaling, and is effective against this type of cancer.

Front 355

Which types of cancers have the strongest association with tobacco exposure?

Back 355

Squamous Cell CarcinomaSmall-Cell Carcinoma

Front 356

Describe how exposure to tobacco smoke leads to morphological changes progressing to cancer.

Back 356

Particularly in squamous cell carcinoma...Innocuous basal cell hyperplasiaSquamous cell metaplasiaSquamous dysplasiaCarcinoma in situInvasive cancer

Front 357

Describe SCLCs histologically.

Back 357

Scant cytoplasmSmall hyperchromatic nuclei with fine chromatin patternNucleoli indistinctDiffuse sheets of cells

Front 358

Describe NSCLC histologically.

Back 358

Abundant cytoplasmPleomorphic nuclei with coarse chromatin patternNucleoli often prominentGlandular or squamous architecture

Front 359

In which, SCLC or NSCLC, is it more common to find neuroendocrine markers, such as dense core granules, expression of chromogranin, neuron-specific enolase and synaptophysin?

Back 359

SCLC

Front 360

In which type of lung cancer is mucin present?

Back 360

NSCLC - adenocarcinomas

Front 361

What kinds of peptide hormones are produced in SCLCs?

Back 361

Adrenocorticotropic hormoneADHGastrin-releasing peptideCalcitonin

Front 362

What kinds of peptide hormones are produced in NSCLCs?

Back 362

PTH-related peptide in SCC

Front 363

Describe the distribution and etiology of SCCs

Back 363

More common in men than womenClosely correlated with smokingTend to arise centrally in major bronchiSpread to local hilar nodes

Front 364

What causes cavitation in lung cancers?

Back 364

The lesions may undergo central necrosis, causing them to fall in on themselves

Front 365

What are some morphologies that precede SCC?

Back 365

Squamous metaplasia or dysplasiaCarcinoma in situ

Front 366

Describe the morphology of SCCs

Back 366

A well defined tumor mass, may obstruct lumen of a major bronchus and cause distal atelectasis and infectionRange from well-differentiated squamous cell neoplasms with keratin pearls and intercellular bridges, to poorly differentiated neoplasms having only residual squamous cell features.

Front 367

What is an adenocarcinoma (in the lung)?

Back 367

A NSCLCMay occur as a central lesion but usually are more peripheral. Many arise in relation to peripheral lung scars (causal or secondary?)Adenocarcinomas are most common in women and nonsmokers - grow slowly, form smaller masses than others, metastasize widely at an early stage, and assume a variety of forms.

Front 368

What are the three general forms of adenocarcinoma?

Back 368

Acinar (gland forming)PapillarySolid types

Front 369

Describe the putative precursor of peripheral adenocarcinomas.

Back 369

Atypical adenomatous hyperplasia - recognized as a well-demarcated focus of epithelial proliferation composed of cuboidal to low-columnar cells resembling Clara cells or type 2 alveolar pneumocytes which demonstrate various degrees of cytologic atypia. Lesions are monoclonal, share many molecular aberrations associated with adenocarcinomas like KRAS mutations.

Front 370

What is a bronchioloalveolar carcinoma?

Back 370

A subtype of adenocarcinoma - they involve peripheral parts of the lung, either as a single nodule or as multiple diffuse nodules that may coalesce to produce pneumonia-like consolidation.

Front 371

What is the key feature of a BAC?

Back 371

A BAC, or bronchioloalveolar carcinoma, is most noted for growth along preexisting structures and preservation of alveolar architecture. They grow in a monolayer along the alevolar septa, which serves as a scaffold for their lepidic growth pattern (like butterflies on a fence).

Front 372

What are the two subtypes of BACs?

Back 372

Mucinous and NonmucinousMucinous - comprising tall, columnar cells with prominent cytoplasmic and intra-alveolar mucin

Front 373

What is a proposed mechanism through which some invasive adenocarcinomas of the lung arise?

Back 373

Atypical adenomatous hyperplasia-bronchioloalveolar carcinoma-invasive adenocarcinoma sequence

Front 374

What are bronchoalveolar stem cells?

Back 374

A population of multipotent cells at the bronchoalveolar duct junction - they undergo expansion after peripheral lung injury and replenish the normal cell types found there - like bronchiolar Clara cells and alveolar cells. It is possible that BASCs incur the initiating oncogenic event and these cells escape normal 'checkpoint' mechanisms, resulting in pulmonary adenocarcinomas.

Front 375

What are large-cell carcinomas?

Back 375

Undifferentiated malignant epithelial tumors that lack the cytologic features of SCCs and glandular or squamous differentiation. They typically have large nuclei, prominent nucleoli, and a moderate amount of cytoplasm. Possibly represent SCCs or adenocarcinomas that are so poorly differentiated that they can no longer be recognized by microscopy.

Front 376

What are small-cell lung carcinomas?

Back 376

SCLCs generally appear as pale gray centrally located masses without extension into the lung parenchyma and early involvement of the hilar and mediastinal nodes.

Front 377

Describe the tumor cells found in SCLCs.

Back 377

SCLCs are composed of tumor cells with a round to fusiform shape, scant cytoplasm, and finely granular chromatin.Mitotic figures are frequently seen, and despite the appellation of "small" the neoplastic cells are usually twice the size of resting lymphocytes.There is necrosis, and the cells are markedly fragile, often showing fragmentation and "crush artifact" in small biopsy specimens.

Front 378

From what type of cell is an SCLC derived, and what are some special characteristics?

Back 378

They are derived from neuroendocrine cells, and express a variety of neuroendocrine markers, in addition to a host of polypeptide hormones. There is nuclear molding from close apposition of tumor cells that have scant cytoplasm.

Front 379

What is a Pancoast tumor?

Back 379

An apical neoplasm, which may cause symptoms by pressing on important structures. There are a variety of clinical symptoms - some includes destruction of the 1st and 2nd ribs, sometimes thoracic vertebrae, etc.

Front 380

Describe the clinical course of a carcinoma of the lung.

Back 380

They tend to be silent, insidious lesions that more often than not have spread so as to be unresectable before they produce symptomsChronic expectoration and cough may be the sole symptoms. Other problems may include hoarseness, chest pain, superior vena caval syndrome, pericardial or pleural effusion, or persistent segmental atelectasis or pneumonitis.By then, usually the prognosis sucks. Tumor presents with symptoms emanating from metastatic spread to the brain, liver, or bones - although the adrenals may be nearly obliterated, adrenal insufficiency (Addison disease) is uncommon because islands of cortical cells sufficient to maintain adrenal function usually persist.

Front 381

Which as a better prognosis, NSCLC or SCLC?

Back 381

NSCLC

Front 382

Why are NSCLCs more treatable than SCLCs?

Back 382

NSCLCs may be detected before metastasis or local spread, cure is possible by lobectomy or pneumonectomySCLCs tend to have metastasized, and surgical resection is not an option. They are sensitive to chemotherapy, but inevitably recur. Median survival is 1 year.

Front 383

What are some paraneoplastic syndromes associated with lung cancer?

Back 383

3-10% of lung cancer patients will get...Hypercalcemia (oversecretion of PTH-related peptide)Cushing syndrome (increased adrenocorticotropic hormone)SIADHNeuromuscular syndromes like myasthenic syndrome, peripheral neuropathy, polymyositisClubbing of fingers, hypertrophic pulmonary osteoarthropathyHematologic manifestations, including migratory thrombophlebitis, nonbacterial endocarditis, and DIC

Front 384

What paraneoplastic syndrome is most commonly associated with SCC? Adenocarcinomas?

Back 384

SCC - hypercalcemiaAdenocarcinoma - hematologic syndromes

Front 385

From what cells do bronchial carcinoids originate?

Back 385

Thought to arise from Kulchitsky cells (neuroendocrine cells) that line the bronchial mucosa and resemble intestinal carcinoids.These cancer cells contain dense-core neurosecretory granules in their cytoplasm and rarely may secrete hormonally active polypeptides. May occur as part of the multiple endocrine neoplasia syndrome.

Front 386

Describe the prognosis for bronchial carcinoids.

Back 386

Appear at an early age (around 40 years) and represent about 5% of all pulmonary neoplasmsThey are often resectable and curable.

Front 387

Describe the morphology of bronchial carcinoids.

Back 387

Originate in main-stem bronchi and grow in one of two patterns - obstructing polypoid, spherical, intraluminal mass; or a mucosal plaque penetrating the bronchial wall to fan out in the peribronchial tissue (callar-button llesion)

Front 388

Describe the histology of bronchial carcinoids.

Back 388

Composed of nests of uniform cells that have regular round nuclei with "salt and pepper" chromatin, absent or rare mitoses, and little pleomorphism.

Front 389

Describe the histology/morphology of an atypical bronchial carcinoid.

Back 389

A carcinoid that displays a higher mitotic rate, increased cytologic variability, and focal necrosisHigher incidence of lymph node and distant metastasis than "typical" carcinoids and fare worse. 20-40% have p53 mutations.

Front 390

What are some typical clinical presentation symptoms specific to bronchial carcinoids?

Back 390

They present with finding related to their growth, so hemoptysis, cough, recurrent bronchial and pulmonary infections.Some are asymptomatic, and discovered by chance on CXRCarcinoid syndrome - intermittent attacks of diarrhea, flushing, and cyanosis.

Front 391

What are two important primary disorders of the lung?

Back 391

Primary intrapleural bacterial infectionsPrimary neoplasm of the pleura known as a malignant mesothelioma

Front 392

What is the most common cause of fluid in the pleural cavity?

Back 392

Hydrothorax from CHF

Front 393

What kind of fluid in the pleural cavity suggests pleuritis?

Back 393

An exudate characterized by protein content > 2.9 gm/dL and inflammatory cells

Front 394

What are the four principal causes of a pleural exudate?

Back 394

Microbial invasion through either direct extension of a pulmonary infection or blood borne seeding (suppurative pleuritis or empyema)Cancer (bronchogenic carcinoma, metastatic neoplasms to the lung or pleural surface, mesothelioma)Pulmonary infarctionViral pleuritisLess commonly: SLE, rheumatoid arthritis, uremia, previous thoracic surgery.

Front 395

What is a common underlying cause of hemorrhagic pleuritis in patients older than 40, who are afebrile, in no pain, and have a negative PPD?

Back 395

Cancer

Front 396

What is pneumothorax, and how does it occur?

Back 396

Pneumothorax refers to air or other gas in the pleural sac. May occur in young, healthy individuals without any known pulmonary disease (simple or spontaneous pneumothorax) or as the result of some thoracic or lung disorder (secondary pneumothorax) like emphysema or a fractured rib.

Front 397

What are some pulmonary lesions close to the pleural surface which may cause secondary pneumothorax?

Back 397

EmphysemaLung abscessTuberculosisCarcinomaMechanical ventilatory support with high pressure may also trigger secondary pneumothorax

Front 398

Describe a ball-valve leak and the complication it produces with pneumothorax.

Back 398

It may create a tension pneumothorax that shifts the mediastinum. Compromise of pulmonary circulation may follow and even be fatal - if the leak seals and the lung is not re-expanded within a few weeks, so much scarring may occur that it can never b e fully re-expanded. Serous fluid collects and creates hydropneumothorax, and the lung becomes vulnerable to infection.

Front 399

What is Hemothorax?

Back 399

A collection of whole blood in the pleural cavity - a complication of a ruptured intrathoracic aortic aneurysm that is almost always fatal. The blood will clot within the pleural cavity, making it more complicated.

Front 400

What is Chylothorax?

Back 400

A pleural collection of a milky lymphatic fluid containing microglobules of lipid - the total volume of fluid may not be large, but chylothorax is always significant because it implies obstruction of the major lymph ducts, usually by an intrathoracic cancer.

Front 401

What is a malignant mesothelioma?

Back 401

Rare cancer of mesothelial cells - usually arising in the parietal or visceral pleura (also in peritoneum, pericardium).Mostly from asbestos exposure.

Front 402

Describe the morphology of a malignant mesothelioma.

Back 402

Starts with extensive pleural fibrosis and plaque formationThese tumors begin in a localized area and then spread widely, and lung tends to become ensheathed in a yellow-white firm sometimes gelatinous layer of tumor that obliterates the pleural space.

Front 403

What are the three morphological patterns of malignant mesotheliomas?

Back 403

Epithelial - in which cuboidal cells line tubular and microcystic spaces, into which small papillary buds project. Most common pattern.Sarcomatoid - spindled and sometimes fibroblastic-appearing cells grow in nondistinctive sheetsBiphasic - both sarcomatoid and epithelioid areas

Front 404

What somatic mutations have been observed in malignant mesotheliomas?

Back 404

p16/CDKN2A on chromosome 9p21 and NF2 on chromosome 22q12

Front 405

With what virus are nasopharyngeal carcinomas strongly associated?

Back 405

EBV - it is found in nearly all nasopharyngeal carcinomas.

Front 406

What are the three histological variants of nasopharyngeal carcinomas?

Back 406

Keratinizing squamous cell carcinomaNonkeratinizing squamous cell carcinomaUndifferentiated carcinoma*Undifferentiated carcinoma is the most common and most closely linked with EBV

Front 407

What are some characteristics of an undifferentiated nasopharyngeal carcinoma

Back 407

Large epithelial cells with indistinct cell borders (syncytial growth) and prominent eosinophilic nucleoliAlso there is a strong influx of mature lymphocytes, giving these neoplasms the other name lymphoepitheliomas - despite the fact the lymphocytes are not part of the neoplastic process, nor are the tumors benign.

Front 408

What is the nature of a nasopharyngeal carcinoma?

Back 408

It invades locally, spreads to cervical lymph nodes, and then metastasizes to distant sites. Tend to be raadiosensitive, and the 5 year survival rates are 50% even for advanced cancers.

Front 409

What are some common tumors of the larynx? Most common presentation?

Back 409

Vocal cord nodulesPapillomasSquamous cell carcinomasPresentation: Hoarseness

Front 410

What is a vocal cord nodule (polyp)?

Back 410

Smooth, hemispherical protrusions - usually less than 0.5cm in diameter, located on the true vocal cords. Composed of fibrous tissue, covered by stratified squamous mucosa, usually intact but can be ulcerated by contact trauma with the other vocal cord. Lesions occur in heavy smokers or singers, suggesting they are the result of chronic irritation or abuse.

Front 411

What is a laryngeal papilloma or squamous papilloma of the larynx?

Back 411

A benign neoplasm, usually on the true vocal cords, that forms a soft, raspberry-like excrescence rarely more than 1cm in diameter.

Front 412

Describe the histology of a laryngeal papilloma or squamous papilloma of the larynx.

Back 412

These small benign neoplasms tend to consist of multiple slender finger-like projections supported by central fibrovascular cores and covered by an orderly, typical, stratified squamous epithelium. Trauma may lead to ulceration, hemoptysis

Front 413

What is recurrent respiratory papillomatosis?

Back 413

RRP - recurring, multiple papillomas in children - they are caused by HPV types 6 and 11, and do not become malignant. Often they spontaneously regress at puberty. Cancerous transformation is rare.Infection probably occurs via vertical transmission.

Front 414

Describe the etiology of carcinoma of the larynx.

Back 414

Usually in those 40+ years old, males (7:1 ratio). Environmental influences are important - almost all cases occur in smokers; Alcohol and asbestos may play a role.Most are squamous cell lesions, rarely adenocarcinomas. The tumor develops on the vocal cords (glottic tumors) or below the cords.

Front 415

Describe the histology of carcinoma of the larynx.

Back 415

Usually follows the typical progression of squamous cell carcinoma. They begin as in situ lesions that later appear as pearly gray, wrinkled plaques on the mucosal surface, ultimately ulcerating and fungating. Glottic tumors are usually keratinizing, well-to-moderately differentiated squamous cell carcinomas. Nonkeratinizing, poorly differentiated carcinomas may be seen as well.

Front 416

How does carcinoma of the larynx present clinically? What is the prognosis?

Back 416

Typically manifests with persistent hoarseness. The location of the tumor has a significant effect on prognosis - about 90% are confined to the larynx at diagnosis. There is sparse lymphatic supply as well. Therefore these types aren't so difficult to treat.The subglottic tumors may be clinically quiet and present later. 1/3 mortality - usually from infection of the distal respiratory passages or widespread metastases and cachexia.

Front 417

What are the four morphological divisions of the study of kidney disease?

Back 417

GlomeruliTubulesInterstitiumBlood Vessels

Front 418

What is Azotemia?

Back 418

An elevation of blood urea nitrogen and creatinine levels and is largely related to a decreased GFR.

Front 419

What is prerenal azotemia?

Back 419

Encountered when there is hypoperfusion of the kidneys, which decreases GFR in the absence of parenchymal damage.

Front 420

What is postrenal azotemia?

Back 420

Urine flow is obstructed below the level of the kidney. Relief of the obstruction is followed by correction of azotemia.

Front 421

Describe uremia.

Back 421

When azotemia progresses to clinical manifestations and systemic biochemical abnormalities.Characterized by failure of renal excretory function, but also by a host of metabolic and endocrine alterations incident to renal damage. There may also be secondary gastrointestinal, neuromuscular, and cardiovascular involvement.

Front 422

Briefly describe acute nephritic syndrome.

Back 422

A glomerular syndrome dominated by the acute onset of usually grossly visible hematuria, mild to moderate proteinuria, azotemia, edema, and hypertension - the classic presentation of acute post-streptococcal glomerulonephritis.

Front 423

Briefly describe nephrotic syndrome.

Back 423

A glomerular syndrome characterized by heavy proteinuria ( > 3.5gm/day), hypoalbuminemia, severe edema, hyperlipidemia, lipiduria.

Front 424

Briefly describe asymptomatic hematuria/proteinuria.

Back 424

This is the manifestation of subtle or mild glomerular abnormalities.

Front 425

Briefly describe rapidly progressive glomerulonephritis.

Back 425

Results in loss of renal function in a few days or weeks and is manifested by microscopic hematuria, dysmorphic red blood cells, red blood cell casts in urine sediment, and mild-to-moderate proteinuria.

Front 426

Briefly describe acute renal failure.

Back 426

Dominated by oliguria or anuria, resent onset azotemia. Results from glomerular injury (crescentic glomerulonephritis), interstitial injury, vascular injury, acute tubular necrosis.

Front 427

Briefly describe chronic renal failure.

Back 427

Characterized by prolonged symptoms and signs of uremia, and is the end result of all chronic renal diseases.

Front 428

Briefly describe urinary tract infection.

Back 428

Characterized by bacteriuria and pyuria. Infection may be symptomatic or asymptomatic, and may affect the kidney or bladder only.

Front 429

Briefly describe nephrolithiasis.

Back 429

Manifested by renal colic, hematuria, and recurrent stone formation.

Front 430

Describe the structures in the glomerular capillary wall.

Back 430

Thin layer of fenestrated endothelial cellsGBM with a thick, electron-dense central layer, the lamina densa, and thinner, electron-lucent peripheral layers, the lamina rara interna and lamina rara externa. GBM mostly contains collagen type IV, laminin, polyanionic proteoglycans, fibronectin, and others.Visceral epithelial cells (podocytes) - structurally complex, interdigitating, with foot processes separated and bridged by a thin slit diaphragm of nephrin.Mesangial cells - a basement membrane-like mesangial matrix that forms a meshwork through which mesangial cells are scattered.

Front 431

List the seven main primary glomerular diseases.

Back 431

Minimal-change diseaseFocal and segmental glomerulosclerosisMembranous nephropathyAcute postinfectious GNMembranoproliferative GNIgA nephropathyChronic GN

Front 432

List some glomerulopathies secondary to systemic diseases.

Back 432

Lupus nephritis (SLE)Diabetic nephropathyAmyloidosisGN secondary to lymphoplasmacytic disordersGoodpasture syndromeMicroscopic polyangiitisWegener's granulomatosisHenoch-Schonlein purpuraBacterial endocarditis-related GNGN secondary to extrarenal infectionThrombotic microangiopathy

Front 433

What are a few hereditary glomerular diseases?

Back 433

Alport SyndromeFabry DiseasePodocyte/Slit-diaphragm protein mutations

Front 434

What are two forms of antibody-associated injury of the glomerulus?

Back 434

Injury resulting from deposition of soluble circulating antigen-antibody complexes in the glomerulusInjury by antibodies reacting in situ within the glomerulus, either with insoluble fixed (intrinsic) glomerular antigens or with molecules planted within the glomerulus.

Front 435

What organisms may cause circulating immune complex-mediated disease from glomerular disease/injury?

Back 435

StreptococcusHepatitis BPlasmodium falciparumTreponema pallidum

Front 436

Describe the contents of a glomerular lesion from antigen-antibody complexes.

Back 436

Leukocytic infiltration into glomeruliVariable proliferation of endothelial, mesangial, and parietal epithelial cells. There may be electron-dense deposits/clumps of immune complexes.