Robbin 15 and 16

Question 1

_ is a defective development of both lungs resulting in decreased wt, vol, and acini for body wt and gestational age. It is caused by _

Answer 1

pulmonary hypoplasia, caused by anything that compress the lungs or impede normal lung expansion in utero such as congenital diaphragmatic hernia and oligohydramnios.

Question 2

Foregut cysts are abnormal detachments of primitive foregut and most often located in _

Answer 2

hilum and middle mediastinum

Question 3

The walls of bronchogenic cyst contains _

Answer 3

bronchial glands, cartilage and smooth muscle, usually present due to compression of nearly structures or found incidentally.

Question 4

what is pulmonary sequestration?

Answer 4

discrete area of lung tissue that 1) lacks any connection to airway system and 2) has an abnormal blood supply arising from the aorta or its branches.

Question 5

extralobar and intralobar sequestration differ by their presentation how?

Answer 5

Extralobar external to the lung and come to attention in infants as a mass lesion. Intralobar occur within lung and present in older kids often due to recurrent localized infection or bronchiectasis.

Question 6

Atelectasis differs in infants vs adults how?

Answer 6

Infants = incomplete expansion
Adults = collapse of previously inflated lung creating areas of airless parenchyma

Question 7

Adult or acquired atelectasis produces a well _ regions but poorly _, predisposing for infection.

Answer 7

well perfused. poorly ventilated

Question 8

Adult or acquired atelectasis comes in what three flavors?

Answer 8

1. Resorption atelectasis
2. Compression atelectasis
3. Contraction atelectasis.

Question 9

_ atelectasis is a consequence of complete obstruction without impairment of blood flow

Answer 9

Resorption

Question 10

In resorption atelectasis, decreased lung volume results in a mediastinal shift to which side?

Answer 10

affected side

Question 11

What are some causes of resorption atelectasis?

Answer 11

mucous plug associated with asthma, bronchitis, aspiration pneumonia, foreign body etc.

Question 12

_ is consequence of partially or totally filled pleura with exudate (CHF), tumor, air (pneumothorax), blood (hemothorax), when air pressure threatens the function of lungs and great vessels (tension peumothorax), or with an extra-pulmonary mass compressing lung parenchyma

Answer 12

Compression atelectasis

Question 13

In compression atelectasis, compression pushes lung and results in a mediastinal shift to which side?

Answer 13

away from the affected side

Question 14

what is contraction atelectasis?

Answer 14

Fibrotic changes prevent expansion, resulting in reduced lung volume and ventilation. This is the only irreversible atelectasis.

Question 15

_ is the accumulation of fluid in alveolar space due to either 1) increased capillary hydrostatic pressure, 2) decreased capillary oncotic pressure or 3) an increased vascular permeability

Answer 15

Pulmonary edema

Question 16

1 is due to increased hydrostatic pressure and most commonly associated with 2 sided congest heart failure.

Answer 16

1. Hemodynamic pulmonary edema.

2. Left

Question 17

In _ pulmonary edema basal regions develop edema first (dependent edema) b/c pressure is great in dependent areas, and alveolar macrophages have hemosiderin in them called siderophages or heart failure cells. As this progresses fibrosis and thickening of the affected areas results in a gross brown and firm appearance called brown induration

Answer 17

hemodynamic

Question 18

_ is a type of edema that is dependent on an increased capillary permeability

Answer 18

microvascular injury pulmonary edema.

Question 19

Microvascular injury pulmonary edema is most commonly associated with _

Answer 19

pneumonia. but can also be caused by inhaled gases (O2, smoke) liquid aspiration (near-drowning) or trauma

Question 20

In microvascular injury pulmonary edema, edema begins in 1 and then moves into 2

Answer 20

1. vascular ednothelium

2. alveoli

Question 21

_ can result from the extreme case of microvascular injury pulmonary edema

Answer 21

acute respiratory distress syndrome

Question 22

What are some morphological findings of acute respiratory distress syndrome?

Answer 22

acute gross = heavy, firm, red, and boggy lungs
Acute histo: interstitial and interalveolar edema, inflammation (neutrophils), hyaline membrane = fibrin rich edema with cytoplasmic/lipid remnants

Question 23

_ is a manifestation of severe acute lung injury characterized by abrupt onset of significant hypoxemia and bilateral pulmonary infiltrates in the absence of cardiac failure

Answer 23

Acute respiratory distress syndrome

Question 24

In the pathogenesis of ARDS, list the chain of events from initiation to resolution

Answer 24

1. Endothelial activation: injury sensed by resident alveolar macrophages which secretes mediators such as TNF. these mediators can directly injury endothelial cells or activate endothelial cells to express increased levels of adhesion molecules procoagulant proteins and chemokines
2. Adhesion and extravasation of neutrophils: neutrophils adhere to activated endothelium and migrate into interstitium and alveoli and release inflammatory mediators including ROS, and cytokines. Macrophages migration inhibitory factor (MIF) also helps to sustain ongoing inflammation –> increased recruitment and adhesion of leukocytes, causing more endothelial injury, local thrombosis
3. Accumulation of intraalveolar fluid and formation of hyaline membranes. damage to type II alveolar cells –> surfactant abnormalities –> compromise gas exchange. Ultimately the debris of dead cells forms hyaline membranes
4. Resolution of injury is impeded in ALI/ARDs due to epithelial necrosis and inflammatory damage that impairs ability of remaining cells to assist with edema resorption. If inflammatory stimulus is lessened, macrophage remove intraalveolar debris and release fibrogenic cytokines such as TGFb and PDGF which stimulate fibroblast and collagen deposition leading to fibrosis of alveolar walls. Bronchiolar stem cells proliferate to replace pneumocytes.

Question 25

what are some causes of ARDS?

Answer 25

- infection (pneumonia, sepsis (typically gram negative sepsis) - aspiration - acute pancreatitis - trauma with shock - amniotic fluid embolism - uremia

Question 26

How to patients with ARDS present clinically?

Answer 26

- Profound dyspnea and tachypnea | - cyanosis and hypoxemia, respiratory failure and appearance of diffuse bilateral infiltrates on Xray.

Question 27

How is ARDS treated?

Answer 27

- respiratory support and treat underlying cause - mechanical ventilation with low tidal volume - PEEP (positive end-expiratory pressure) to prevent airway collapse at end expiration, recruits collapsed alveoli. together increases FRC and decrease shunting

Question 28

_ is widespread acute lung injury associated with rapidly progressive clinical course. Usually occurs age 59. Patients presents with acute respiratory failure often following an illness of less than 3 wks duration that resembles an URI

Answer 28

Acute interstitial pneumonia

Question 29

_ lung disease are characterized by an increase in resistance to airflow due to partial or complete obstruction at any level from the trachea and larger bronchi to the terminal and respiratory bronchioles.

Answer 29

Obstructive

Question 30

FEV1/FVC ratio less _ generally indicates airway obstruction

Answer 30

0.7

Question 31

_ is characterized by reduced expansion of lung parenchyma and decreased total lung capacity

Answer 31

restrictive disease

Question 32

In restrictive lung disease FEV1/FVC ratio is _

Answer 32

normal

Question 33

Restrictive lung disease occur in what two broad conditions?

Answer 33

1. chest wall disorders ( severe obesity, pleural disease, kyphoscoliosis, and neuromuscular disease such as poliomyelitis 2. chronic interstitial and infiltrative disease such as pneumoconioses and interstitial fibrosis.

Question 34

Emphysema, chronic bronchitis, asthma and bronchiectasis are all what kind of lung disease?

Answer 34

Obstructive Lung disease

Question 35

What two lung diseases are often grouped as COPD?

Answer 35

emphysema and chronic bronchitis, because most patients have features of both since major trigger is smoking

Question 36

_ is characterized by irreversible enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls without obvious fibrosis leading to increased work to breathe

Answer 36

Emphysema

Question 37

Emphysema is classified into what four types?

Answer 37

1. centriacinar (most common, 95%) 2. panacinar 3. paraseptal 4. irregular 1 and 2 causes clinically significant airflow obstruction

Question 38

In centriacinar emphysema, which part of the respiratory bronchioles are affected?

Answer 38

central or proximal parts of the acini. distal alveoli are spared. Lesion are more severe in upper lobes, particularly in the apical segments. Normal and emphymatous airspaces coexist within the same acinus and lobule

Question 39

In this form of emphysema, the acini are uniformly enlarged from the level of respiratory bronchiole to the terminal blind alveoli. Associated with a1-antitripsin deficiency

Answer 39

panacinar (panlobular) emphysema. The entire acinus is affected, not the entire lung. Affects lower lobes, esp bases.

Question 40

in distal acinar (paraseptal) emphysema which parts of the acini are spared and which parts are affected?

Answer 40

central and proximal parts are spared and distal alveoli are affected. Forms along the pleura and lobule margins adjacent to fibrosis or scarring. may form cyst like structure associated with penumothorax in young adults

Question 41

this form of emphysema is asymptomatic, clinically insignificant, almost always found on autopsy and irregular pattern of alveolar enlargement always is associated with scarring.

Answer 41

Irregular emphysema

Question 42

How does emphysema appear grossly on morphology?

Answer 42

Large, voluminous lungs with hyperinflation (well developed pan- and centri) and bullae/blebs associated (distal acinar emphysema)

Question 43

How does emphysema appear microscopically?

Answer 43

Abnormally large alveoli separated by thin septa, large alveoli from trapped air. - pores of Kohn are so large that septae seem to float in alveoli - blood vessels are compressed by emphysematous alveoli

Question 44

Explain the pathogenesis of development of emphysema

Answer 44

Smoking and other noxious particles cause lung damage and inflammation. Factors include: - inflammatory mediators and leukocytes (Leukotriene B4, IL8, TNF etc) --> epithelial damage and structural change - protease- antiprotease imbalance. relative deficiency of protective antiprotease which in some are genetic in basis. - Oxidative stress. substances from tobacco smoke, alveolar damage and inflammatory cells all produce oxidants, which may beget more tissue damage and inflammation. Proven in mouse model with NRF2 gene mutation. NRF2 target genes are all associated with smoking-related lung disease in humans. - Infection: does not initiate it but exacerbates the disease process

Question 45

The idea that proteases are important is based in part on the observation that patients with a genetic deficiency of _ have markedly enhanced tendency to develop pulmonary emphysema which is compounded by smoking.

Answer 45

Antiprotease a1-antitrypsin (AAT) which normally inhibits action of elastase and so without AAT elastase is unchecked and destroys the elastic tissue of the alveoli

Question 46

emphysema is a condition characterized by dilation of air spaces with _1 (dec or inc)_ elasticity and _2 (dec or inc)_ compliance

Answer 46

1. decreased | 2. Increased

Question 47

which type of emphysema is commonly due to smoking? due to AAT deficiency?

Answer 47

``` Smoking = Centriacinar AAT = panacinar , smoking exacerbates ```

Question 48

what are the signs, symptoms and physical findings of emphysema?

Answer 48

- signs and Symptoms: dyspnea, classic pursed-lip breathing; - Physical findings: decreased breath sounds on auscultation, increased anterior-posterior diameter (barrel chest), hyperresonant to percussion, flattened diaphgram on Xray - decreased diffusion capacity --> increased ventilatory rate --> normal ABG - patients will lean forward, have a prolonged expiration through pursed lips. Pink Buffer (end stage) - impaired expiratory airflow measured through spirometry

Question 49

How is emphysema treated?

Answer 49

- smoking cessation, ambulatory O2 | - bronchodilators, inhaled steroids, oral/IV steroids and antibiotics

Question 50

A 50-year-old Caucasian male presents to the Emergency Department complaining of shortness of breath and unintentional weight loss over the past several months. On physical examination, the patient appears quite thin and breathes through pursed lips. Breath sounds are decreased in all lung fields. The patient's chest x-ray shows increased A-P diameter. Which of the following findings is expected on spirometry? 1. Increased FEV1 2. Decreased FEV1/FVC 3. Decreased TLC 4. Normal FEV1 but increased FVC 5. Normal lung values

Answer 50

2. Decreased FEV1/FVC The patient described is suffering from Chronic Obstructive Pulmonary Disease (COPD), specifically emphysema. In emphysema, both FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) are decreased, however, FEV1 is decreased more, therefore FEV1/FVC is decreased.

Question 51

A patient with a1-antitrypsin deficiency is warned by his physician that his increasing dyspnea may be worsened by his continued cigarette smoking. Which of the following factors, released by both neutrophils and alveolar macrophages, is responsible for the patient's condition? 1. Major Basic Protein 2. Antibodies against alpha-3 segment of collagen IV (COL4A3) 3. Mucus 4. Surfactant 5. Elastase

Answer 51

5. elastase The patient is suffering from emphysema caused by his genetic disorder, a1-antitrypsin deficiency. This condition can be worsened by smoking-mediated increased release of elastase from macrophages and neutrophils.

Question 52

what causes do emphysema patients usually die of?

Answer 52

1. coronary artery disease 2. respiratory failure 3. Right sided heart failure 4. massive collapse of lungs secondary to pneumothorax

Question 53

_ is a term used to designate dilation of alveoli in response to loss of lung substance elsewhere. It is best exemplified by hyperexpansion of residual lung parenchyma following surgical removal of a diseased lung or lobe

Answer 53

Compensatory hyperinflation

Question 54

_ is expansion of lung because of trapped air but without septal wall destruction.

Answer 54

Obstructive overinflation

Question 55

what are common causes of obstructive overinflation?

Answer 55

tumor or foreign objects, asthma with: 1) partial obstruction = ball - Valve allows air in but not out; and 2) complete obstruction + collateral air flow through pores of Kohn

Question 56

Bullous emphysema is term for large subpleural blebs or bullae that can occur in any form of emphysema near apex, sometimes near TB scars. What is the occasional complication associated with it?

Answer 56

pneumothorax

Question 57

Interstitial emphysema is entrance of air into _

Answer 57

connective tissue stroma of lung, mediastinum or subQ tissue

Question 58

what is interstitial emphysema caused by?

Answer 58

alveolar tears (cough + alveolar obstruction as in empysema), punctures, or trauma or mechanical ventilation

Question 59

_ is defined as persistant cough with sputum production for at least 3 months in at least 2 consecutive years, in absence of any other cause.

Answer 59

chronic bronchitis. common among smokers and polluted cities. Falls in one end of the sepctrum of COPD

Question 60

Primary or initiating factor in the genesis of chronic bronchitis is exposure to noxious inhaled substances such as tobacco smoke and dust from grain, cotton, and silica. Explain the pathogenesis that follows

Answer 60

- Mucus hypersecretion (IL13, histamine) in large airways, hypertrophy of submucosal glands in trachea and bronchi --> increased goblets cells and mucous production - Inflammation --> cellular damage involving neutrophils, lymphocytes and macrophages --> inflammation/fibrosis --> chronic airway obstruction - Infection: does not initiate but exacerbates disease process

Question 61

Explain the pathophysiological changes seen in chronic bronchitis

Answer 61

- imbalance or proteinase/anti-proteinases, inflammation, oxidative stress, and inhibited repair processes, - central and peripheral airways involved - results in hyperplasia of bronchiolar mucus glands and fibrosis of terminal bronchioles - ciliary dysfunction

Question 62

what are two most common cause of chronic bronchitis?

Answer 62

- smoking | - cystic fibrosis

Question 63

what are some signs and symptoms of chronic bronchitis?

Answer 63

Symptoms: dyspnea, productive cough PE: wheezing and crackles on auscultation, prolonged expiration, classic pursed lip breathing, - Blue bloater (end stage): chronic alveolar hypoxia leads to pulmonary HTN, edematous due to right heart failure; cyanosis of skin

Question 64

How is chronic bronchitis treated?

Answer 64

- conservative: smoking cessation, home O2 - Pharmacological: bronchodilators and inhaled steroids for long term maintenance; systemic steroids and abx for acute exacerbations; roflumilast for severe disease

Question 65

_ is a chronic disorder of the conducting airways, usually caused by an immunological reaction, which is marked by episodic bronchoconstriction due to increased airway sensitivity to a variety of stimuli; inflammation of bronchial walls; and increased mucus secretion

Answer 65

asthma

Question 66

_ is manifested by recurrent episodes of wheezing, breahtlessness, chest tightness and cough, particularly at nigh and/or in the early morning

Answer 66

asthma

Question 67

what are the two categories of asthma

Answer 67

1. Atopic : allergen sensitization and immune activation, positive family history 2. Non-atopic: no evidence of allergen sensitization. Family history is less common. In either can have diverse triggers such as infection, irritants, cold air, stress, exercise, and even drugs such as aspirin

Question 68

Atopic asthma is most common type and is a classic example of _ hypersensitivity reaction

Answer 68

IgE-mediated (Type I)

Question 69

_ can be used to diagnose actopic asthma.

Answer 69

high total serum IgE levels or evidence of allergen sensitization by serum radioallergosorbent tests (RAST)

Question 70

How do patient's with aspirin-sensitive asthma present?

Answer 70

Occur in pts with recurrent rhinitis and nasal polyps, they experience an asthmatic attack and urticaria. Attack is triggered by inhibiting COX pathway leading to rapid decrease in prostaglandin E2 which normally inhibits enzymes that generate proinflammatory mediators like leukotrienes B4, C4, D4, and E4 which are thought to be the major players in aspirin-induced asthma

Question 71

Explain the pathogenesis of atopic asthma

Answer 71

- Caused by exaggerated TH2 responses to normally harmless environmental antigens in genetically predisposed people. TH2 secrete cytokines (IL4, IL5, IL13) and other cytokines such as IL17 and IL19 that promote inflammation and stimulate B cells to produce IgE and other Ig. --> airway dysfunction via release of potent inflammatory mediators and remodeling of airway wall --> increased local secretion of GF, induction of mucus glands hypertrophy, smooth muscle proliferation, angiogenesis, fibrosis and nerve proliferation.

Question 72

Explain the acute/early response of atopic asthma

Answer 72

- airborne antigens react first with mast cells on epithelial surface causing an increased permeability, access to submucosal mast cells, enhanced type 1 response. - direct stimulating of subepithelial vagal (parasympathetic) receptor resulting n constriction - sum total in bronchoconstriction, edema, mucous secretion

Question 73

Explain the late phase response in atopic asthma

Answer 73

- - swarm of leukocytes (eosinophils, neutrophils, and more T cells (TH17)) drawn by chemotactic factors from mast cells, airway epithelium, and vascular endothelium and other leukocytes - Eosinophils major basc protein = epithelial damage and airway constriction

Question 74

What are the major mediators that which play a role in asthmatic attack

Answer 74

- major bronchospasm mediators such as Leukotrienes C4, D4, and E4 prolongs bronchoconstriction and increased vascular permeability and increased mucus secretion; acetylcholine which can also bronchoconstrict - minor bronchoconstriction and vasodilators: histamine; prostaglandins D2; platelet activating factor. these factors are more important in chronic or nonallergic asthma - unknown role but suspected: IL1, IL6, and TNF alpha are proinfllammatory cytokines

Question 75

Polymorphism in what gene has the strongest and most consistent association with asthma or allergic disease?

Answer 75

IL13 on chromosome 5q

Question 76

Polymorphism in gene encoding _ a metaloproteinase may be linked to increased proliferation of bronchial smooth muscle cell and fibroblast, thus contributing to bronchial hyperreactivity and subepithelial fibrosis

Answer 76

ADAM33

Question 77

Increased serum levels and expression of _ are correlted with asthma severity, airway remodeling, and decreaesd pulmonary function

Answer 77

YKL-40, a chitinase-like glycoprotein expressed and secreted by many cells

Question 78

Although infection is not a cause or trigger for asthma, URI with what virus has a 10 to 30 fold increased risk of devleoping persistent and/or severe asthma?

Answer 78

rihonovirus type C and RSV

Question 79

A characteristic finding in sputum or bronchoalveolar lavage specimens of asthmatic patients include_

Answer 79

1. Curschmann spirals which may result from extrusion of mucus plugs from subepithelial mucous gland ducts or bronchioles; 2) Charcot-Leyden crystals composed of eosinophil protein called galectin 10

Question 80

What specific changes are taken place in "airway remodeling" as seen in asthma

Answer 80

- thickening of airway wall - subbasement membrane fibrosis - increase in size of submucosal glands and number of airway goblet cells - hypertrophy and/or hyperplasia of bronchial wall muscle

Question 81

How does a patient with asthma attack present?

Answer 81

cardinal signs are: chest tightness, dyspnea, wheezing and coughing (w/wo sputum production) triggered by bronchospasm that can spontaneously resolve or resolve with intervention. - Attacks last minutes to hours - in most severe form (status asthamaticus) where ventilatory function can be impaired (and fatal), asthma symptoms may last for hours to day and are refractory to retreatment

Question 82

How is an asthma attack diagnosed?

Answer 82

- increaed in airflow obstruction from baseline, - difficulty with exhalation - peripheral blood eosinophilia and finding of eosinophils, curschman spirals, and charcot leyden crystal in sputum

Question 83

_ is a disorder in which destruction of smooth muscle and elastic tissue by chronic necrotizing infections leads to permanent dilation of bronchi and bronchioles

Answer 83

Bronchiectasis

Question 84

what are some causes of bronchietasis?

Answer 84

- congential or hereditary conditions including CF (secondary to infection with pseudomonas or aspergillus), intralobar sequestraiton of lung, immunodeficiency states, and primary ciliary dyskinesia and kartagener syndromes - Infection, including necrotizingpneumonia (common are aspergillus which is common to CF or asthma pts) - Bronchial obstruction due to tumor, foreign bodies, or mucus impaction; in each instance the bronchietasis is localized to obstructed lung segment - - Associated with other disease such as rheumatoid arthritis, SLE, IBD, COPD, postransplantation - 1/4-1/2 of cases are idiopathic

Question 85

Obstruction and infection are the major conditions associated with bronchiectasis. What are the predisposing factors that which leads to bronchiectisis?

Answer 85

1. CF: defective ion transport leads to defective mucocilary action and airway obstruction by thick viscous secretion --> infection --> widespread damage to airway walls --> destruction of supporting smooth muscle and elastic tissue -> dilated bronchi and obliterated bronchioles. --> fibrosis (bronchiolitis obliterans) 2. Primary ciliary dyskinesia: autosomal recessive with cilary dysfunction due to defects in ciliary motor proteins contributes to retention of secretion and recurrent infection --> bronchiectasis. These pts also develop Kartagener syndrome due to abnormal ciliary function which is needed for organ development in chest and abd. Kartagener syndrome is marked by situs inversus or partial lateralizing abnormality associated with bronchietasis and sinusitis 3. Allergic bronchopulmonary aspergillosis occurs in pts with asthma and cystic fibrosis who develop periods oexacerbation and remission that may led to proximal bronchietasis and fibrotic lung disease. High association with aspergillus fumigatus senstization which leads to activation of TH2 and that recruits eosinophils and other leukocytes.

Question 86

Explain the gross and histologic finding of bronchietecsis

Answer 86

Gross: lower lobes bilaterally unless caused by a focal obstruction (tumor or foreign body aspiraiton) in which case there are focal lesion; airways are dilated up to 4x, some ares look like cysts filled with pus Histologic: acute inflammatory exudate associated with desquamination of epithelium or even ulcerations; chronic - pseudostratification and squamous metaplasia, almost always with fibrosis, organism can be cultured at any phase, often H influenze or aspergillus

Question 87

How does bronchiectasis present clinically?

Answer 87

- severe, persistent cough; expectoration of foul smelling, sometimes bloody sputum; dyspnea nad orthopnea in severe cases; on occastion hemoptysis. paroxysms of cough are frequent when pt rises in the morning as the change in position causes collections of pus and secretion to drain into bronchi. - Obstructive respiratoyr insuffieciency can led to marked dyspnea and cyanosis. - due to modern therapy mortality is decreased and cor pulmonale, brain abscess, amyloidosis are less frequent complications

Question 88

The classic functional abnormalities of restrictive lung disease include _

Answer 88

- reduction in diffusion capacity - reduction in lung volume - reduction in lung compliance These eventually leads to right sided heart failure associated with cor pulmonale

Question 89

_ refers to a clinicopathologic syndrome marked by progressive interstitial pulmonary fibrosis and respiratory failure

Answer 89

Idiopathic pulmonary fibrosis (IPF)

Question 90

What environmental factors and genetic factors are associated with IPF?

Answer 90

1. Environmental factors: smoking, metal fumes, wood dust, farming, hair dressing, and stone polishing. All these cause recurrent alveolar epithelial cell damage 2. Genetic factors: Most people who smoke or have other environmental exposure do not get the disease thus indicating there is a genetic link. (A) Germline loss of function mutation in TERT and TERC which encode components of telomerase. 15% of familial IPF have telomerase gene defects and 25% of sporadic IPF are associated with abnormal telomerase shortening; (B) mutation gene for surfactant--> folding defects --> activating of unfolded protein response to type II pneumocytes --> pneumocytes more susceptible to environmental insults; (C) increased secretion of MUC5B, a mucin that make alveolar epithelial cells susceptible to injury or exaggerated downstream events leading to fibrosis - these injuries to alveolar cells set in motion event that lead to increase local production of fibrogenic cytokines such as TGF-b

Question 91

IPF is a disease of older people, rarely appearing before the age of _

Answer 91

50.

Question 92

In the pathway to fibrosis as seen in IPF, activated fibroblasts exhibit signaling abnormalities that lead to increased signaling through which pathway?

Answer 92

PI3K/AKT pathway

Question 93

Explain how IPF appear grossly and histologically

Answer 93

Gross: lungs are cobblestoned, due to retraction of scars along the interlobular septa. Cut surface shows firm, rubbery white areas of fibrosis which occur in subpleural regions along interlobular septa preferentially. Histo: patchy interstitial fibrosis. Early: fibroblastic foci. later: honeycomb fibrosis (hyperplastic type II pneumoncytes or bronciolar epithelium)

Question 94

what are the clinical signs of IPF?

Answer 94

- starts insidiously with gradual increasing dyspnea on exertion and dry cough. Most are 55-75 of age. - hypoxemia, cyanosis and clubbing occur in late course - 3 yrs survival rate - tx: lung transplant

Question 95

why is it important to distinguish a patient with nonspecific interstitial pneumonia vs interstitial pneumonia?

Answer 95

Nonspecific interstitial pneumonia pts have a better prognosis with proper treatment

Question 96

Histologically nonspecific interstitial pneumonia is divided into cellular and fibrosing patterns. Explain the difference

Answer 96

Cellular: mild to moderate chronic interstitial inflammation with lymphocytes and few plasma cells in uniform or pathcy distribution Fibrosing: diffuse or patchy interstitial fibrotic lesions of roughly same stage of development.

Question 97

Clinically how to pts with nonspecific interstitial pneumonia present?

Answer 97

- dyspnea, cough of several months - female in their 6th decade - on CT: bilateral symmetric, lower lobe reticular opacities - younger pts with cellular patterns vs fibrosing pattern have better prognosis

Question 98

What are the characteristic clinical and histologic findings of cryptogenic organizing penumonia?

Answer 98

aka bronchiolitis obliterans organizing pneumonia (this name is nor preferred). - Clinical: cough, dyspnea, patchy subpleural or peribronchial areas of airspace consolidation on radiograph. - histo: polypoid plugs of loose organizing CT (Masson bodies) within alveolar ducts, alveoli, and bronchioles. CT are all same age and lung architecture is normal. No interstitial fibrosis (Note: if there is fibrosis then it's probably due to infection or inflammatory injury of lungs and prognosis depends on underlying cause), and no honeycomb lung. - pts recover spontaneously, tho some may need steroid for up to 6 months

Question 99

what autoimmune diseases commonly have pulmonary involvement?

Answer 99

- Rheumatoid arthritis (RA) (30-40% have pulm involvement) - SLE - Scleroderma

Question 100

What pulm disorders are associated with RA?

Answer 100

- chronic pleuritis w/wo effusion - diffuse interstitial pneumonitis and fibrosis - intraplulm rheumatoid nodules - follilcular bronchiolitis - pulm HTN

Question 101

What pulm disorders are associated with scleroderma?

Answer 101

- diffuse interstitial fibrosis (nonspecific interstitial pattern more common) - pleural involvement

Question 102

what pulm disorders are associated with SLE

Answer 102

- patchy, transient parenchymal infiltrates, or occasional severe lupus pneumonitis - pleurisy and effusion

Question 103

What is Pneumoconioses defined as?

Answer 103

inhalation of small dust particles (coni = latin for dust)

Question 104

What factors determine the development of penumoconiosis?

Answer 104

1. amount of dust retained in lung and airways - dust concentration in air, and retainment in lung is influenced by smoking that destroys mucociliary clearance 2. size, shape, and buoyancy of particles. Most dangerous size are 1-5 microns cuz these are able to reach terminal airway 3. Particle solubility and physiochemical reactivity. Small particles of injurious substance with high solubility are more likely to cause acute lung injury. Larger ones resist dissolution and my persist within lung for years -->evoke fibrosing cllagenous pneumoconioses as seen in silicosis 4. possible additional effects of other irritants 5. substance that activate inflammasome amplify the intensity and duration of local reaction cuz they activate both innate and adaptive immune response 6. Tobacco makes it all worse esp asbestos 7. Genetic predisposition.

Question 105

Coal worker's pneumoconiosis ranges from asymptomatic form known as _ 1_to progressive massive fibrosis where contaminated _2_ in the coal dust favor the progressive disease.

Answer 105

1. antracosis | 2. silica

Question 106

Coal worker's pneumoconiosis (CWP) ranges from asymptomatic form known as _ 1_to progressive massive fibrosis where contaminated _2_ in the coal dust favor the progressive disease.

Answer 106

1. antracosis | 2. silica

Question 107

How is simple coal worker's pneumoconiosis characterized by?

Answer 107

Coal macules and coal nodules. Coal macules are carbon-laden macrophages; nodules also contain a delicate network of collagen fibers, upper lob es (high ventilation) and upper zone of the lower lobes.

Question 108

Rheumatoid nodules in lungs can be complicated by coal worker's penumoconiosis in a syndrome called __

Answer 108

Caplan's syndrome

Question 109

1-2 cm fibrotic centers is seen what form of coal worker's pneumoconiosis?

Answer 109

Complicated CWP

Question 110

What are clinical findings of CWP?

Answer 110

- usually benign causing little decrement in lung fxn. - progressive massive fibrosis leads to pulm htn, and cor pulmonale. - No association with lung cancer - no susceptibility to TB - once advanced disease is reached, no further exposure to coal dust does not improve course, like silicosis

Question 111

pertinent epidemiology of silicosis include _

Answer 111

- workers in foundaries, sandblasting, mining industries, repair, rehabilitation or demolition of concrete - African Americans at higher risk than whites

Question 112

Explain the pathogenesis of silicosis

Answer 112

- crystalline form more fibrogenic such as quartz | - after inhalation its phagocytosed by macrophages --> inflammasome --> release of inflammatory mediators IL1, IL18.

Question 113

Silicosis commonly found in what part of the lung?

Answer 113

Hilar lymph nodes and upper zones of lungs

Question 114

Silicosis starts off as tiny barely palpalble pale blackened nodules in the hilar lymph nodes and upper zones of lungs, but as it progresses it forms _

Answer 114

Hard, collagenous scars where some can forms central softening and cavitation due to superimposed TB or ischemia.

Question 115

_ is Characteristic finding on radiograph of progressive silicosis

Answer 115

eggshell calcification as sheets of calcification in lymph nodes.

Question 116

The histologic findings of silicosis include _

Answer 116

central area of whorled collagen fibers with more peripheral zone of dust laden macrophages. These can be polarized to find birefringent silicate particles (silica is weakly birefringent)

Question 117

Explain the clinical course of silicosis

Answer 117

- on radiograph: fine nodularity in upper zone. - pulm fxn either normal or only moderately affected early on with no SOB until progressive massive fibrosis supervenes. - impair macrophages function --> increased susceptibility to TB unlike CWP - DOUBLES THE RISK OF DEVELOPING LUNG CANCER

Question 118

Localized fibrous plaques or rarely diffuse pleural fibrosis, recurrent pleural effusion, parenchymal interstitial fibrosis, lung carcinoma, mesothelioma, laryngeal, ovarian cancers, all have been implicated to chronic exposure to _

Answer 118

asbestos

Question 119

Asbestos occur in two forms serpentine and amphibole. 1) Which one is responsible for 90% of exposure as it's used in industry? and 2) which one is less common but more pathogenic in that it induces mesothelioma.

Answer 119

1. Serpentine - more likely to cleared by mucociliary action 2. Amphibole - small enough to reach lung instersitium quickly by escaping mucociliary action Note: both are equally fibrogenic, nonetheless

Question 120

Explain how smoking and asbestos exposure are synergistic

Answer 120

- both are oncogenic, mediated by free radicals generated by both - The carcinogen in tobacco smoke onto asbestos fibers is the basis for synergy for developing lung carcinoma. - smoking destroys mucociliary action thus making asbestos easier to make it down to lung parenchyma. - risk of carcinoma is increased by 55 fold with both

Question 121

Explain how injury occurs with asbestos exposure.

Answer 121

Once phagocytosed by macrohagess, asbestos fibers activate inflammasome and stimulate and release proinflammatory factors and fibrogenic mediators - Starts in bifurcation of small airways and ducts where they land and penetrate. - macrophages and alveolar/interstitial macrophages tries to clear the fibers. long term exposure leads to persistent release of mediators, ROS, protease, cytokines, growth factors --> interstitial pulmonary inflammation and interstitial fibrosis

Question 122

how is diffuse pulmonary interstitial fibrosis from asbestos distinguished from fibrosis from other pneumoconiosis?

Answer 122

Presence of asbestos bodies which are golden brown, fusiform or beaded rods with translucent center and consistent of asbestos fibers coated with an iron-containing proteinaceous material - Ferruginous bodies may be also seen (iron-coated protein comlex)

Question 123

_ are the most common manifestation of asbestos exposure, and are well circumscribed plaques of dense collagen found on anterior and posterolateral aspect of parietal pleura and over domes of diaphragm.

Answer 123

Pleural plaques. --> restrictive lung disease -= normal FEV1/FVC ratio and low FVC

Question 124

Asbestosis affects which parts of the lung most commonly?

Answer 124

Lower lobes including entire respiratory unit

Question 125

What drugs are commonly known to cause fibrosis and drug induced lung disease?

Answer 125

- bleomycin (chemo) - amiodarone ---> pneumonitis - illict IV drugs

Question 126

Radiation induced lung disease is pretty common can manifest as acute radiation pneumonitis (lymphocytic alveolitis or hypersensitivity pneumonitis) 1-6 months after irradiation, manifested with fever, dyspnea out of proportion to the volume of lung, pleural effusion and infiltrates that usually corresponds to area of irradiation. Presence of what cells are characteristic of radiation damage?

Answer 126

Atypia of hyperplastic type II cells and fibroblasts. Epithelial cell atypia and form cells within vessel walls in particular are characteristic.

Question 127

Sarcoidosis presents in many clinical patterns, but most common, 90% of cases, occur where?

Answer 127

bilateral hilar lymphadenopathy or lung involvement

Question 128

Pertinent epidemiology of sarcoidosis include _

Answer 128

- female adults younger than 40 - Southeast U.S. - Blacks 10x more than whites - rate in chinese and southeast asians.

Question 129

What kind of lung diseases does sarcoidosis cause?

Answer 129

restrictive most common. Obstructive or mixed pattern is also seen

Question 130

Sarcoidosis _1_mediated disease, particularly _2_ T cells resulting ratio of _3 / _ rraning from 5:1 to 15:1. Leads to increased levels of T-cell derived TH1 cytokines such as _4_ and _4_ which may be responsible for T cell expansion and macrophage activation. Impaired of _5_ cell function is also noted

Answer 130

1. T cell 2. CD4 3. CD4/CD8. 4. IL2, IFNy 5. Dendritic

Question 131

What genetic influence are seen in development of sarcoidosis?

Answer 131

HLA genotypes (e..g HLA-A1 and HLA-B8)

Question 132

Morphologically in sarcoidosis, nonnecrotizing granulomas composed of aggregates of epitheliod macrophages is common, although central necrosis is unusual. Additionally, laminated concretions composed of calcium and protein known as _ 1_and stellate inclusion known as _2_ are found within giant cells in 60% of cases.

Answer 132

1. Schaumann bodies | 2. Asteroid bodies

Question 133

Sarcoidosis is discovered incidentally on radiograph. Initially, most often patient medical attention due to what symptoms?

Answer 133

- respiratory symptoms such as SOB, cough, chest pain, hemoptysis or constitutional signs like fever, fatigue, wt loss, anorexia night sweats.

Question 134

What are symptoms of sarcoidosis

Answer 134

- Cough, fever, malaise, arthritis main in ankle and legs. - can be GRUELING (Granulomas, Rheumatoid arthritis, Uveitis, Erythema nodosum, Lymphadenopathy, Interstitial fibrosis, Negative TB, Gammaglobuinemia)

Question 135

Physical findings of sarcoidosis include _

Answer 135

- Skin lesions: nodular granulomatous lesions, facial rash, erthyma nodosum, eye lesions (uveitis), enlarged salivary and lacrimal glands

Question 136

A 31 year-old African-American female presents with a painful shin nodules, uveitis, and calcified hilar lymph nodes. A transbronchial biopsy of the lung would most likely show which of the following histologies? 1. Inflammation, fibrosis and cyst formation that is most prominent in subpleural regions 2. Silica particles (birefringent) surrounded by collagen 3. Golden-brown fusiform rods 4. Patchy interstitial lymphoid infiltrate into walls of alveolar units 5. Non-caseating granulomas

Answer 136

5. Non-caseating granulomas. The clinical presentation in this vignette is most likely sarcoidosis. Biopsy of the lung in this patient would show non-caseating granulomas.

Question 137

A 38-year-old African American female presents to her primary care physician with uveitis, cough, and arthralgias in her ankles and legs. Bloodwork reveals elevated angiotensin converting enzyme levels, and skin PPD testing shows no observable induration after 48 hours. The patient demonstrates reduced FEV1 and FVC upon spirometry. FEV1/FVC is 85%. Which of the following would you expect to see upon chest X-ray: 1. Enlarged hilar lymph nodes 2. Kerley B Lines 3. Bilateral diaphragmatic elevation. 4. Pleural effusion 5. Fluid in alveolar walls

Answer 137

1. Enlarged hilar lymph nodes The clinical presentation is consistent with sarcoidosis. Enlarged hilar lymph nodes are commonly seen on chest radiographs of patients with sarcoidosis.

Question 138

what findings suggests that hypersensitivity pneumonitis is an immunologically mediate disease

Answer 138

- increased levels of proinflammatory chemokines such as protein 1a and IL8, CD4, CD8, ab against causative agents, complement and Ig within vessel walls, presence of noncreasting granulomas (Tcell mediated - Type IV hypersenstivity)

Question 139

what are the clinical features of hypersensitivity pneumonitis?

Answer 139

- acute attack followed by recurring episodes of fever, dyspnea, cough, and leukocytosis. - Micronodular interstitial infiltrates on chest radiograph, and pulmnary fxn show acute restrictive disorder - symptoms appear within 4-6 and lasts for 12hrs to several days - chronic exposure --> progressive resp failure, dyspnea, and cyanosis decreased in TLC and compliance

Question 140

What is pulmonary eosinophilia?

Answer 140

- pathologic pulmonary entities characterized by an infiltration of eosinophils, recruited in part by elevated alveolar levels of eosinophils attracts such as IL5

Question 141

What are the different types of pulmonary eosinophilia?

Answer 141

1. Acute eosinophilic pneumonia with respiratory failure: rapid onset of fever, dyspnea, hypoxemic respiratory failure. Responds to corticosteroids 2. Secondary eosinophiliaphilic pneumonia: occur in parasitic, fungal, andbacterial infeciton; in hypersensitivity, pneumonitis, drug allergies; asthma, aspergillosis, vasculitis (churg-strauss) 3. Idiopathic chronic eosinophilic pneumonia: focal area of cellular consolidation around periphery lung fields. aggreagates of lymphocytes and eosinophils in both septal walls and alveolar spaces. Cough, fever, night sweats, dyspnea and wt loss. Responds to corticosteroid therapy.

Question 142

_ is characterized by large collection of macrophages in airspaces in a current or former smoker,

Answer 142

Desquamative interstitial pneumonia

Question 143

Morphologically, the characteristic finding of desquamative interstitial pneumonia includes _

Answer 143

accumulation of large number of macrophages with abundant cytoplasm containing dusty brown pigment (smokers' macrophages)

Question 144

How does desquamative interstitial pneumonia present?

Answer 144

- presents in 4th or 5th decade of both men and women - dyspnea, cough, over weeks to months, often associated with clubbing of digits - reduction of diffusing capacity of CO2. - excellent response to steroid therapy and cessation of smoking

Question 145

_ is marked by chronic inflammation and peribronchiolar fibrosis, common histologic lesion in cigarette smokers characterized by presence of pigmented intraluminal macrophages within 1st and 2nd order respiratory bronchioles. Morphologically smoker's macrophages are seen.

Answer 145

Respiratory bronchiolitis-associated interstitial lung disease. Symptoms: gradual onset of dyspnea and cough

Question 146

Pulmonary Langerhan cell histiocytosis is a rare disease characterized by focal collections of Langerhans cells and sometimes with eosinophils, seen in young smokers, with cystic and nodular abnormalties seen on imaging. To diagnose, they can be tested for cluster of differentiations and ribosome. What CD are they positive for?

Answer 146

Positive for CD1a, and CD207 (langerin). negative for CD68. Also positive for S100. Some have activating mutations in serine/threonine kinase BRAF.

Question 147

Pulmonary alveolar proteinosis (PAP) is a rare disease caused by defects related to _

Answer 147

granulocyte-macrophage colony-stimulating factor (GM-CSF) or pulmonary macrophage dysfunction that results in accumulation for surfactant in intra-alveolar and bronchiolar spaces. Presents as autoimmune PAP, secondary PAP, and hereditary PAP (mutation disrupt genes involved in GM-CSF signaling).

Question 148

Autoimmune PAP is caused by circulating neutralizing antibodies specific for _

Answer 148

GM-CSF. Occurs primarily in adults, 90% of all cases of PAP, with no family predisposition.

Question 149

Secondary PAP is associated with diverse disease such as _1_ and is speculated that is due to inadequate clearance of _2_

Answer 149

1. hematopoietic disorders, malignancies, immunodeficiency disorders, lysinuric protein intolerance and acute silicosis and others. 2. surfactant from alveolar spacs

Question 150

what are the morphologic findings of PAP?

Answer 150

- homogeneous, granular precipitate containing surfactant proteins within alveoli, causing focal to confluent consolidation - increase in size and wt of lung

Question 151

what is the standard of care for PAP?

Answer 151

- whole long lavage. | - GM-CSF therapy effective in more than 1/2 pts with autoimmune PAP

Question 152

what mutations are implicated in surfactant dysfunction disorders?

Answer 152

1. ATP-binding cassette protein member 3 (ABCA3) - most common mutation in this disease. Presents first few months of life with rapidly progressive resp failure and death 2. Surfactant protein C - second most common. autosomal dominant 3. Surfactant protein B: least common -occur in infants. infants are usually full term and rapidly develops progressive respiratory distress shortly after birth. death 3-6 monts

Question 153

Small lamellar bodies with electron dense cores are diagnostic for which mutational form of surfactant dysfunction disorder?

Answer 153

ABCA3

Question 154

what's defined as pulmonary HTN?

Answer 154

Pulmonary artery pressure greater than 25mmHg or greater than 30 mmHg during exercise. (normal is 10-14)

Question 155

pulmonary HTN is classified into what 5 groups according to WHO

Answer 155

1. pulm artery htn involving small pulm muscular arteries 2. pulm htn secondary to left sided failure 3. pulm htn stemming from lung parenchymal disease or hypoxemia 4. chronic thromboembolic pul htn 5. pulm htn of multifactorial basis

Question 156

what are common causes of pulm htn?

Answer 156

1. Chronic obstructive or interstitial lung disease (WHO gr 3) --> inc resistance --> inc pulm BP 2. Antecedent congenital or acquired heart disease, e.g. ASD, VSD (WHO gr 2) 3. Recurrent thromboemboli (WHO gr 4): reduces cross-sectional area of pulm vasculature --> inc resistance 4. Autoimmune disease (gr 1) esp SLE -> inc resistance 5. Obstructive sleep apnea (gr 3) is a common disorder that is associated with obesity and hypoxemia.

Question 157

In the pathogenesis of pulm htn, idopathic or familial pulm artery hypertention has been noted. Mutation in _ gene predispose to abnormal vasculature, increasing the risk of developing pulm HTN

Answer 157

BMPR2, which is a cell surface protein belonging to TGF-b receptor superfamily, which binds to a variety of cytokines, including TGF-b, BMP, activin, and inhibin. Normally acts to inhibit smooth muscle growth, mutated gene leads to increased secretion of vasoconstrictors and decrease secretion of vasodilators.

Question 158

A 73-year-old female is hospitalized following a pelvic fracture. She undergoes surgical repair without complication. Four days into her hospital stay, she develops acute dyspnea and chest pain accompanied by oxyhemoglobin desaturation. Which of the following arterial blood gas values is the patient most likely to have? 1. pH 7.5, PaO2 60, PaCO2 30, HCO3 22 2. pH 7.3, PaO2 60, PaCO2 30, HCO3 20 3. pH 7.5, PaO2 60, PaCO2 50, HCO3 28 4. pH 7.3, PaO2 60, PaCO2 50, HCO3 24 5. pH 7.4, PaO2 60, PaCO2 40, HCO3 24

Answer 158

1. pH 7.5, PaO2 60, PaCO2 30, HCO3 22 The patient in this vignette most likely has a pulmonary embolism (PE) secondary to a deep vein thrombosis (DVT). Classically, a PE results in a hypoxic, respiratory alkalosis.

Question 159

A 68-year-old female presents to the emergency room with acute onset of dyspnea and hemoptysis. Her past medical history is unremarkable and she has had no prior surgeries. A ventilation-perfusion scan demonstrates a large perfusion defect that is not matched by a ventilation defect in the left lower lobe. Which of the following would you also expect to find in this patient: 1. Pleuritic chest pain 2. Bradycardia 3. Aortic dilation 4. Claudication 5. Increased inspiratory capacity

Answer 159

1. Pleuritic chest pain The patient’s symptoms and ventilation-perfusion scan results are consistent with pulmonary embolism (PE). Pleuritic chest pain is a common presenting symptom.

Question 160

As part of diffuse pulmonary hemorrhage syndrome, In goodpasture syndrome , circulating antibodies (against a3 chain of collagen IV) initiate inflammatory destruction of _

Answer 160

pulmonary alveoli giving rise of necrotizing hemorrhagic interstitial pneumonitis Most cases occur in male teens or in their 20s who smoke. Linked to HLA-DRB1*1501 and *1502

Question 161

10 yr old boy presents with sudden onset of productive cough and hemoptysis. Lab revealed he is anaemic and on imaging diffuse pulmonary infiltration were shown. NO other abnormalities were found. Pt responded well to immunosuppression therapy with prednisone and azathioprine. What is the likely diagnosis

Answer 161

Idiopathic pulmonary hemosiderosis.

Question 162

A 62-year-old Caucasian male presents to your office with hemoptysis and hematuria. On physical exam you note a saddle nose deformity. Laboratory results show an elevated level of cytoplasmic antineutrophil cytoplasmic antibody. Which of the following interventions is most appropriate for this patient? 1. Smoking cessation 2. IV immunoglobulin 3. Corticosteroids 4. Isoniazid 5. Discontinuation of ibuprofen

Answer 162

3. Corticosteroids This patient's presentation is consistent with granulomatosis with polyangiitis (Wegener's granulomatosis). GPA is appropriately treated with cyclophosphamide and corticosteroids.

Question 163

A 45-year-old man is brought to the emergency room by his wife who reported that he coughed up blood earlier that morning. He has had a chronic fever, weight loss, and blood in his urine over the past couple of weeks, but refused to see a doctor until now. Upon work up, it was determined that an autoimmune disorder of unknown origin that causes inflammation of the blood vessels characterized by focal necrotizing vasculitis necrotizing granulomas in the lung and upper airway. In making this diagnosis, what is the best location for biopsy?

Answer 163

Transbronchial lung biopsy Pt has polyangiitis with granulomatosis

Question 164

A 55-year-old male presents to his primary care physician complaining of bloody nasal discharge and hemoptysis. His past medical history is notable for hypertension. Medications include metoprolol and amlodipine. Physical examination is notable for oral ulcers and inflamed conjunctiva. Serum creatinine is 3 mg/dL. Creatinine was 0.95 mg/dL during an office visit one year ago. IF shows the results of immunostaining for C-ANCA. Which of the following is the most likely diagnosis? 1. Microscopic polyangiitis 2. Polyarteritis nodosa 3. Takayasu’s arteritis 4. Giant cell arteritis 5. Granulomatosis with polyanginitis (formerly Wegener's granulomatosis)

Answer 164

5. Granulomatosis with polyanginitis (formerly Wegener's granulomatosis) The patient’s symptoms, including upper respiratory symptoms, evidence of pulmonary involvement via hemoptysis, and renal failure as indicated by a severe rise in creatinine, are consistent with granulomatosis with polyanginitis (GPA).

Question 165

Germline mutation in MyD88 is associated with _

Answer 165

destructive bacterial (pneumococcal) pneumonias. MyD88 is an adaptor for several TLRs that is important for activation of transcription factor NFkB

Question 166

Cell-mediated immune defects (congenital and acquired) leads to increased infection with what kind of bacteria?

Answer 166

Intracellular microbes such as mycobacteria and herpesviruses as well as microorganisms of very low virulence such as pneumocystis jiroveci

Question 167

What are some biomarkers that which can distinguish between bacterial vs viral pneumonia?

Answer 167

- CRP - procalcitonin both of which are elevated in bacterial more than in viral infections

Question 168

what is the MOST COMMON causative agent of community-acquired acute pneumonia?

Answer 168

Streptococcus pneumoniae

Question 169

What features, seen on culture, supports the diagnosis of streptococcus pneumonia?

Answer 169

presence of many neutrophils containing typical gram+ lancet-shaped diplococci. Note: s pneumoniae is part of normal flora in 20% of pts thus false-positive result can be obtained

Question 170

What groups of pts are high risk of community-acquired pneumonia and what can reduce the risk?

Answer 170

- extremes of age, - Chronic diseases (CHF, COPD, diabetes) - congenital or acquired immune deficiencies, - absent spleen (sickle cell disease or psotsplenectomy puts pts at higher risk of encapsulated bacteriaal infection such pneumonoccus) Pneumococcal vaccines for high risk pt population

Question 171

_ is pleomorphic, gram- organism that occurs encapsulated or nonencapuslated and has six serotypes of the encapsulated form of which type b is the MOST virulent. Do vaccines exist?

Answer 171

Haemophilus influenze. Yes. Common cause of suppurative meningitis in kids up to 5 yrs before the development of a vaccine.

Question 172

While the encapsulated form of H. influenzae is more virulent and can cause pneumonia, nonencapsulated form is less virulent and can cause infection of _. What pt population is at high risk?

Answer 172

Upper respiratory tract, otitis media, sinusitis, bronchopneumonia. Neonates, kids with comorbidities such as prematurity, malignancy, and immunodeficiencies are at high risk.

Question 173

Aside from pnemonia, and URI issues, what other illnesses is H. influenze associated with?

Answer 173

- acute, purulent conjunctivitis in kids - predisposed older pts can get septicemia, endocarditis, pylonephritis, cholescystitis, and supppurative arthritis. - exacerbation of COPD

Question 174

Along with s. pneumoniae, and H. influenzae _ constitutes one of the three most common causes of otitis media in children?

Answer 174

Moraxella catarrhalis

Question 175

What is the second most common cause of acute exacerbation of COPD?

Answer 175

Moraxella catarrhalis. gram(-) cocci

Question 176

_ is an important cause of hospital-acquired pneumonia and is an important cause of secondary bacterial pneumonia in kids and healthy adults following an URI.

Answer 176

Staphylococcus aureus. Associated with high incidence of complication such as lung abscess and emphysema.

Question 177

_ is the most frequent cause of gram- rod bacterial pneumonia. Commonly afflicts debiliated and malnoursihed, and chronic alcohollics. What is the characteristic sputum finding?

Answer 177

Klebsiella pneumoniae. Thick, mucoid, gelatinous (red jelly) often blood tinged, sputum cuz organism produces an abundant viscid capsular polysach, which the pt may have difficulty expectorating.

Question 178

Psudeomonas aeruginosa commonly causes hospital-acquired infections, but related to the respiratory commonly seen what pt population?

Answer 178

cystic fibrosis and immunocompromised pts who are neutropenic. This bug has the propensity to invade blood vessels with consequent extrapulmonary spread --> psudomonas speticemia

Question 179

For Legionella pneumoophila commonly causes pontiac fever, a self-limited URI, but can also cause pneumonia. Explain the following: A. What environment does it flourish B. Mode of transmission C. What pt population legionella pneumonia is commonly seen in D. Mortality rate in immunosuppressed pt E. How is it diagnosed?

Answer 179

A. artifical acquatic environment such as water cooling towers and tubing system of waster supplies. B. Either inhalation of aerosolized organisms or aspiration of contaminated drinking water C. pts with predisposing conditions such as cardiac, renal, immunologic, or hematologic disease, and pts with organ transplant D. 50% E. Legionella antigens in urine or by a positive fluorescent antibody test on sputum. Culture with silver stain is cold standard

Question 180

What kind of environmental is mycoplasma pneumoniae acquired from?

Answer 180

closed communities such as schools, military camps, prisons

Question 181

When it comes to treatment pneumonia, from a clinical standpoint, what two factors are most important?

Answer 181

1. identification of causative agent | 2. determination of extend of disease

Question 182

Morphologically, pneumonia has what two distinct gross anatomic patterns that represent a possible continuum?/

Answer 182

1. Bronchopneumonia = extremely old or extremely young | 2. Lobar pneumonia = previously healthy teens to adults

Question 183

what the gross morphological/histological findings of bronchopneumonia?

Answer 183

- patchy consolidation of lung, conslidation areas of acute supparative inflammation without resolution often with fibrotic granulation tissue. - Grossly appears dry, granular, grey to yellow, poorly delinated areas of lung - histologically: supparative, neutrophil-ric exudate that fills air spaces

Question 184

What are the morphological/histological findings of lobar pneumonia?

Answer 184

- fibrinosupparative consolidation of a large portion of a lobe or an entire lobe. - has 4 stages all with neutrophils involved: 1) Congestion = vascular engorgement , intra-alveolar fluid with few neutrophils in a grossly heavy, boggy, and red lung; 2) Red hepatization = intra-alveolar fluid- mass of RBC, neutrophils, and fibrin with a gross distinctly red, firm, and airless lung (looks like a liver); 3) Grey hepatization = resolution of RBCs, stealing red color, but leaving fibrin, turning the red lung grey. neutrophils predominate; 4) resolution = fibrin+fluid is either organized (fibrinous) or removed by macrophages resulting in a contracted or normal lung. resolution is often complete back to pristine lung with modern abx

Question 185

what complications are associated with pneumonia?

Answer 185

1. tissue destruction and necrosis causing abscess formation (esp common with type 3 pneumonococci or klebsiella infections); 2. spread of infection to pleural cavity causing intrapleural fibrinosuppurative reaction known as empyema; 3. bacteremic dissemination to heart valves, pericardium, brain, kidneys, spleen, or joints causing metastatic abscess, endocarditis, meningitis, or suppurative arthritis

Question 186

Explain the clinical course of pneumonia

Answer 186

- abrupt onset high fever, shaking chills, cough productive of sputum - con induce fibrinosupparative pleuritis = pleuritic chest pain friction rub - Xray shows: a well-circumscribed radio-opaque lobe (lobar pneumonia) or patchy infiltrates throughout lung field (bronchopneumonia) - with abx, disease is controlled, and often fatalities are attributed to complications such as empyema, pleuritis, septicemia

Question 187

which influenza virus type infects humans and are major cause of pandemic and epidemic influenza infections?

Answer 187

Type A

Question 188

_ and _ are components of influenza virus envelope which consissts of lipid bilayer.

Answer 188

Hemogglutinin (H1-H3); Neuromindase (N1, N2)

Question 189

_ is component of influenza virus that seves to attach the virus to it's cellular target via sialic acid residues onsurface polysaccharides

Answer 189

Hemogllutinin

Question 190

_ is component of influenza virus that facilitates release of newly formed virions that are budding from infected cells by cleaving sialic acid residues.

Answer 190

Neurominidase

Question 191

Explain the flu viral genome and what factor determines the virus type

Answer 191

Composed of 8 single-stranded RNA each encoding one or more proteins. The RNA are packed into helices by nucleoprotiens that determine the virus type A, B or C

Question 192

Epidemic of influenza are caused by spontaneous mutation that alter _

Answer 192

antigenic epitopes on viral hemagllutinin and neuromindase proteins (antigenic drift)

Question 193

what causes a flu pandemic?

Answer 193

Antigenic shift. Both the hemagglutinin and neuromindase genes are replaced through recombination with animal influenza viruses

Question 194

Control of viral infection relies on several host mechanism. The resence of viral products induces innate immune responses in fected cells such as production of _1_. These mediators upregulate the expression of _2_ gene which encodes a GTPase that interferes with flu gene transcription and viral replication. Cellular response is eventually augmented by development of antibody response to the viral _3_ proteins

Answer 194

1. alpha and beta interferon 2. MX1 3. Hemaglutinin and neurominidase

Question 195

The avian flu is associated with what strain type?

Answer 195

H5N1

Question 196

_ is a paramyxovirus that causes upper and lower respiratory infections commonly seen in young kids, elderly, and immunocompromised. Signs and symptoms are similar to RSV and often mistaken for flu. Severe infections can cause bronchiolitis and pneumonia

Answer 196

Human metapneumovirus (MPV)

Question 197

What is the only antiviral treatment available for human MPV?

Answer 197

ribavirin

Question 198

Severe acute respiratory syndrome that which first appeared in 2002 is caused by what virus?

Answer 198

Coronavirus

Question 199

Many upper respiratory infections are caused by coronavirus, so what makes SARS special?

Answer 199

It was caused by a new coronavirus (great example of sudden emergence of a new infectious agent), that infected lower respiratory tract and spread throughout the body

Question 200

What are the most common health care-associated pneumonia

Answer 200

Methicilin-resistant staphylococcus aureus and P. aeroginosa. these have higher mortality than those with communnity acquired pneumonia

Question 201

what are most common hospital acquired pneumonia?

Answer 201

gram(+) cocci (mainly s. aureus and s. pneumonia) and gram)-) rods (enterobacteriaeceae and psudomonas species) - seen in pts with prolonged abx use, immunosuppression, ventilator, or indwelling catheters

Question 202

What are some causative agents of atypical "walking" pneumonia?

Answer 202

- Viruses such as influenza A and B; RSV; adenovirus; rhinovirus - Mycoplasma (common in adult) - chlamydia

Question 203

Explain how atypical pneumonias appear morphologically/histologically

Answer 203

Gross: variable = uni/bi lateral, pathyc/total lobe, upper/lower lobes. Aeas affected as red-blue, congested and subcrepitant. Pleuritis and pleural effusion are rare Histo: predominantly interstitial inflammation with monocytes. Intral-alveolar exudate is possible but not common--results from diffuse alveolar damage showing pink hyaline membrane as seen in ARDs

Question 204

How do atypical walking pneumonia pt usually present?

Answer 204

- low fever, headaches, muscle aches | - recent hx of URI + a cough w/o sputum

Question 205

which pts are risk of aspiration pneumonia? and how critical is this type of pneumonia?

Answer 205

Pts with an impaired gag and/or swallowing reflex inhale gastric contents producing both a chemical irritant (gastric acid/decaying food) and a bacterial infection (flora) --> necrotizing - typically follows a fulminant course leading to dead. - those who survive will have lung abscesses (local suppurative process that produces necrosis of lung tissue)

Question 206

what organism commonly results in lung abscess?

Answer 206

aerobic and anaerobic streptococcis, S. aureus, and other gram(-) agents

Question 207

Anaerobic organisms which are normally found in oral cavity, are commonly cultured in lung abscesses. Of these, 60% of cases involve what organisms?

Answer 207

- Bacteroides, fusobacterium and peptococcus species

Question 208

What are some common ways that with lung absecss causative agents can be introduced to the lung?

Answer 208

1. Aspiration of infective material (most common) (seen in acute alcoholism, coma, anesthesia, sinusitis, gingivodental sepsis, debilitation of cough reflex) 2. Antecedent primary lung infection (commonly s. aureus, k. pneumoniae and type 3 pneumonoccucus). transplant and other immunosuppressed are at risk) 3. Septic embolism 4. Neoplasia (postobstructive pneumonia) 5. Other: direct traumatic penetration of lungs; spread of infection from other organs, hematogenous seeding etc

Question 209

What is primary cryptogenic lung abscesses?

Answer 209

presence of lung abscess when all known causes of lung abscess formation have been excluded and no discernible basis for the abscess formation can be identified.

Question 210

Pulmonary abscesses due to aspiration are more common on which lung?

Answer 210

Right (anatomy 101)

Question 211

explain the clinical course of aspiration pneumonia

Answer 211

- much like bronchiectasis - cough, fever, copious amounts of foul-smelling purulent or sanguineous sputum - chest pain and wit loss is common - flubbing of fingers and toes within few weeks - with antimicrobial therapy most resolve leaving behind a scar - complications include: extension to pleural cavity, hemorrhage, development of brain abscesses or meningitis from septic emboli, and secondarily amyloidosis type AA.

Question 212

Chronic pneumonia is most often a localized lesion in immunocompetent with with granulomatous inflammatory reaction caused by _ and _

Answer 212

Bacteria such as tuberculosis; or fungi such as histoplasma capsulatum

Question 213

``` For histoplasmosis explain the following: A. Geological location where it's common B. Clinical findings C. Pathogenesis D. Morphology E. Types ```

Answer 213

A. Ohio/mississippi valley or Spelunking w/ exposure to bats or bird droppings B. Similar to TB, but asymptomatic in most cases. Coin lesions on xray. secondary lung disease in apices with cough, fever, night sweats, wt loss. C. inhaled mold form (microcondidia) from bat or bird droppings; transforms into yeast form and is phagocytized by macrophages, macrophages secrete TNF to recruit and stimulate other macrophage to kill histoplasma. Inhibits oxidative burst and grows intracellularly with eventual lysis. D. Epithelioid granulomas in immunocompromised with coagulative necrosis that produce large areas of consolidation. Healed regions show fibrosis and concentric calcification (tree bark lesions). Histo: presence of methenamine silver strained organism E. 1. Primary and chronic histoplasmosis grey-white granulomas, cough, fever, night sweats, wt loss with calcfication; 2. Disseminated histoplasmosis = no epithelioid granulomas, with focal accumulation of monocytes filled with organisms throughout body

Question 214

Blastomycosis presents in what three clinical forms?

Answer 214

1. Pulmonary blastomycosis 2. Disseminated blastomycosis 3. Primary cutaneous from

Question 215

How does pulmonary blastomycosis present?

Answer 215

Recent visit to Beaver dams (rotting wood) reveals Broad, Based Budding Yeasts on histology that evades phagocytosis and recruits neutrophils. Clinically, abrupt illness with productive cough, headache, chest pain, wt loss, fever, abd pain, night sweats, chills and anorexia.

Question 216

how does blastomycosis appear on chest radiograph

Answer 216

lobar consolidation, multilobar infiltrates, perihiblar infiltrates, multiple nodules, or miliary infiltrates

Question 217

True or false: Almost everyone who inhales spores of coccidoidies immitis become infected and develop a delayed-type hypersensitivity rxn.

Answer 217

True. Infact 80% of people in endmeic areas of SW and Western US and Mexico have positive skin test rxn.

Question 218

What is a possible reason for the infectivity of C. immitis?

Answer 218

infective arthroconidia, when ingested by alveolar macrophages, block fusion of phagosome and lysosome (thus resist intracellular killing) and reproduce intracellularly within a spherule that ruptures releasing infectious organisms and eosinophilia.

Question 219

How do pts with coccidiomycosis present?

Answer 219

Most are asymptomatic. Some get lung lesion, fever, cough, chest pain, erythema nodosum (San Juaquin fever) - recent travels to southwestern US, deserts etc

Question 220

what kind of lung lesions are seen in coccidiomycosis?

Answer 220

Granulomatous lesions such as in TB or histoplasmosis.

Question 221

In an immunocompromised host, pathogens are implicated in pneumonia?

Answer 221

1. Bacteria (p. aeroginosa, mycobacterium sp., L. pneumonphila, and listeria monocytogenes), 2. Virus (CMV, herpes, 3. Fungi (P. jiroveci, candida, aspergillus, phycomycetes, and cryptococus neoformans)

Question 222

An untreated HIV pts is hospitalized with pneumonia in a critical condition. what is the most common/ likely causative agent?

Answer 222

S. Pneumoniae, S. aureus, H. influenzae and gram(-) rods. While opportunistic infections are common, however, most severe pulmonary infections in HIV pts are those caused by the ones listed above. Bacterial pneumonias in HIV are more common, more serious and more often associated with bacteremia than those without HIV

Question 223

For each of the CD4 counts of an HIV pts, indicate what agents are likely the cause of pneumonia: A. >200 B. <200 C. >50

Answer 223

A. bacterial and tubercular infections B. Pneumocystis pneumonia C. CMV, fungal, and mycobacterium avium

Question 224

what are some lung diseases that warrents a lung transplant?

Answer 224

- end stage emphysema - idiopathic pulm fibrosis - CF - idiopathic/familial pulmonary arterial htn

Question 225

In a lung transplant, at what week/month do most infections occur?

Answer 225

3-12th month after transplant

Question 226

What drug can be given prophylatically to reduce risk of CMV infection? to reduce pneumocystis jiroveci infection?

Answer 226

Ganciclovir for CMV | Bactrim for jiroveci

Question 227

A 2 months post-lung transplant pt presents with fever, dyspnea, cough and on imaging shows radiologic infiltrates. What procedure can be performed to accurately diagnose the pts' symptoms?

Answer 227

Pt's symptoms are those of acute rejection. Transbronchial biopsy must be performed to diagnose rejection, since those symptoms are similar to infection

Question 228

what is the major morphologic finding that correlates to chronic rejection?

Answer 228

Bronchiolitis obliterans, partial or complete occlusion of small airways by fibrosis with or without active inflammation. Can't be reversed with tx. Common complication include accelerated pulm arteriosclerosis in graft, and B cell lymphoma. 1 yr survival rate is 79%, 5 yr is 50% and 10yrs is 30%

Question 229

Squamous cell carcinoma of the lung is highly associated with tobacco smoking and also harbors diverse genetic aberration involving chromosome deletions involving tumor suppressor loci. Losses of what loci/gene are known as early events in tumor evolution

Answer 229

3p, 9p (site of CDKN2A gene), and 17p (site of TP53 gene). Squamous cell carcinoma show the highest frequency of TP53 mutations of all histologic types of lung cancinoma. 10% of the time p50 protein overexpression is also an early event. - RB loss is seen in 15% - p16, product of CDKN2A gene is seen in 65% of tumors - recent discoveries show FGFR1 amplification

Question 230

Small cell carcinoma shows the strongest association with smoking and subsequent gene mutations. What genetic mutations associated with small cell carcinoma?

Answer 230

- LOF aberration involving TP53 (75-90%) - LOF of RB (almost 100%) - Chromosome 3p deletion - MYC amplification

Question 231

What genetic mutations are seen in adenocarcinoma of the lung?

Answer 231

- gain of function mutations involving EGFR, ALK, ROS, MET and RET - KRAS (tumors without TK gene mutations)

Question 232

What lung cancer is most common in never smokers?

Answer 232

Adenocarcinoma. More common in women. | - More likely to have EGFR mutations and almost none have KRAS mutation

Question 233

What are the four most common types of lung cancers?

Answer 233

1. Adenocarcinoma (38%) 2. Squamous cell carcinoma (20%) 3. Small cell carcinoma (14%) 4. Large cell carcinoma (3%) 5. Other (25%)

Question 234

What are the four types of morphologic precursor epithelial neoplastic lesions seen in lung?

Answer 234

1. squamous dysplasia and carcioma in situ 2. Atypical adenomatous hyperplasia 3. Adenocarcinoma in situ 4. Diffuse idiopathic pulmonary neuroendocrine

Question 235

For each description/subtype, classify the lung tumors classification it is associated with A. Papillary, clear cell, small cell, basoloid B. Combined small-cell carcinoma C. Minimally invasive adenocarcinoma (non mucinous, mucnous), lepidic, acinar; papillary, solid, mucinous adenocarcinoma D. Large-cell neuroendocrine carcinoma

Answer 235

A. Squamous cell carcinoma B. Small-cell carcinoma C. Adenocarcinoma D. Large cell carcinoma

Question 236

More commonly Adenocarcinomas arise in which part of the lung?

Answer 236

peripheral lung. Compared to squamous cell.

Question 237

Squamous cell carcinoma arise commonly in what part of the lung?

Answer 237

central/hilar region

Question 238

_ are small lesions (less than 5mm) charactrized by dysplastic neumocytes lining alveolar walls that are mildly fibrotic.

Answer 238

Atypical adenomatous hyperplasia

Question 239

_ is less then 3cm and is composed of entirely of dysplastic cells growing along preexisting alveolar septae.

Answer 239

Adenocarcarinoma in situ

Question 240

_ is an invasive mmaligant epithelial tumor with galndular differentiation or mucin production by tumor cells. Can be seen as acinar, lepidic, papillary, micropapillary, and solid with mucin formation.

Answer 240

Adenocarcinoma. Located more on the periphary

Question 241

this type of tumor, there are lepidic pattern of spread in which the tumor cells crawl along normal-appearing alveolar septae and these tumors have scarring and a peripheral lepidic growth pattern called _1_

Answer 241

Being described is a adenocarcinoma. | 1= microinvasive adenocarcinoma. these have better outcome then invasive carcinoma of the same size

Question 242

_ adenocarcinoma tend to spread aerogenously, forming satellite tumors.. can be present as single of multiple nodules resemblling lobar pneumonia

Answer 242

Mucinous adenocarcinoma. Less likely to be corrected with surgery

Question 243

These tumors start off as squamous metaplasia or dysplasia and form carcinoma in situ, and these tumors are commonly found in men and strongly associated with smoking

Answer 243

Squamous cell carcinoma. Can grow exophytically into bronchial lumen and as it grows it can obstruct lumen leading to distal atelectasis and infection. Can also penetrate wall of bronchus and infilrtate along peribronchial tissues - can grow as a cauliflower like intraparenchymal mass

Question 244

Histologically squamous cell carcinomas are charcterized by presence of _

Answer 244

keratinization and/or intercellular bridges

Question 245

_ carcinoma are almost always fatal as they are extremely aggressive and metastasize widely. Has a strong association with smoking (99% of cases are smokers)

Answer 245

Small cell carcinoma

Question 246

The cells of these carcinoma are round, oval, or spindle shaped with prominent nuclear molding. They have scant cytoplasm, ill-defined cell borders, finely granular nuclear chromoatin (salt and pepper pattern), and no or inconspicuous nucleoli.

Answer 246

Small cell carcinoma

Question 247

Which lung cancer is MOST commonly associated with ectopic hormone production?

Answer 247

Small cell carcinoma

Question 248

The occurrence of neurosecretory granules, expression of neuroendocrine markers such as chromogranin, synptophysin, and CD57 suggests that small cell carcinoma are _ cell type in origin

Answer 248

neuroendocrine, which are present in lining of bronchial epithelium

Question 249

In histochemistry of small cell carcinoma, there are high levels of what protein?

Answer 249

antiapoptotic protein (in 90% of tumor)

Question 250

_ is an undifferentiated malignant epithelial tumors. Tumor marker tests will be negative for TTF-1, naspin-A, p63, p40. Most commonly metastases to the bronchial, tracheal, and mediastinal nodes.

Answer 250

Large cell carcinoma. Have large nuclei, prominent nucleoli and some cytoplasm. TTF1-, napsin A are markers for adenocarcinoma; P63 and P40 are markers for squamous cell carcinoma

Question 251

Lung cancers are staged using the International staging system. List the salient features of each category

Answer 251

T: T1 (less than 3cm); T3 >7cm; T4= any tumor with invasion of mediastinum, heart, great vessels, trachea, RLN, esophagus, vertebral body, or carina N: N0 = no mets; N1= ipsilateral hilar nodes; N2 = ipsilateral mediastinal or subcarinal nodes; N3 = metastasis to contralateral mediastinal or hilar nodes M: M0 = no distant mets; M1 = distant mets present (M1a, separate tumor nodule in contralateral lobe, pleural nodules or malignant pleural effusion; M1b = distant mets)

Question 252

In what stage of lung cancer do you start to see metastasis to the ipsilateral hilar nodes?

Answer 252

Stage IIA

Question 253

In what stage do you see metastasis to ipsilateral mediastinum?

Answer 253

Stage IIIA

Question 254

In what stage do you see mets to contralateral side?

Answer 254

Stage IIIB

Question 255

In what stage do yo see distant mets?

Answer 255

Stage IV

Question 256

The following descriptions are characteristics of what type of lung cancer: - Strong link to smoking - more common in men - central (hilar) cavitating lesion - can ectopically secrete PTH-related protein (PTHrP) --> parathyroid-like hypercalcemia and hypophsphatemia - On histo: keratin pearls and IC bridges - Tx: surgical resection (early), chemo and/or radiation (late)

Answer 256

Squamous cell carcinoma

Question 257

The following describes what kind of carcinoma: - most common lung cancer in non smokers females - neuroendocrine in origin - no assocation with smoking

Answer 257

Bronchial adenocarcinoma

Question 258

The following describes what kind of carcinoma: - Cancer of clara cells, mucins-secreting cells or type II pneumocytes. - most cases have an assocation with smoking.

Answer 258

Bronchioalveolar adenocarcinoma

Question 259

The following describes what kind of lung cancer? - most common in men - strong association with smoking - very aggresive - central lesion - associated with ectopic production of ACTH or ADH, Lambert-Eaton syndrome - on histo: stains for enolase, chromograinin, synaptophysin, Kulchitsky cells (small dark blue cells). - Tx: chemo and/or radiaton

Answer 259

Small cell carcinoma

Question 260

The following describes what kind of lung cancer? - strong relationship with smoking - poor prognosis - peripheral or central lesion - associated with gynocomastia and galactorrhea - on Histo: pleomorphic giant cells that are very anaplastic

Answer 260

Large cell carcinoma

Question 261

The following describes what kind of lung cancer? - Hemorrhagic pleural effusion, - psammoma bodies - electron microscopy shows cells with large number of long, slender microvilli, and tonofilmanets

Answer 261

Mesothelioma

Question 262

In general which two lung cancer tend to remain localized longer and have a slightly better prognosis than do the undifferentiated cancers?

Answer 262

Adenocarcinoma and squamous cell carcinoma. The other guys are usually pretty advanced by the time they are discovered

Question 263

Activating mutation in what is associated with rose prognosis regardless of treatment?

Answer 263

KRAS

Question 264

what common paraneoplastic hormones/hormone-like factors are seen in lung cancer?

Answer 264

- ADH --> hyponatremia - ACTH --> cushings - PTH, PTH-related peptide, PGE, cytokines -->hypercalcemia - Calcitonin --> hypocalc - Gonadotropins --> gynocomastia - Serotonin and bradykiinin ---> carcinoid syndrome

Question 265

what is Lambert-Eaton myasthenic syndrome?

Answer 265

systemic manifestation of lung carcinoma, where muscle weakness is caused by autoantibodes directed to the neuronal calcium channel.

Question 266

what systemic paraneoplastic manifestation are seen in lung carcinoma?

Answer 266

- Lambert-eaton myasthenic syndrome - periheral neurophaty - dermatologic abnormalities (acanthosis nigricans) - leukomoid reaction - hypercoagulable state (Trousseu syndrome ) - hypertrophic pulm osteoarthrophaty - Horner syndrome ( due to Pancoast tumors)

Question 267

_ are low-grade malignant epithelial tumors that may arise centrally (fingerlike or spherical polypoid mass that project into lumen of bronchus covered by intact mucosa) or peripherally (collar-button lesion, solid and nodular).. Seen in younger than 40, nonsmoker commonly

Answer 267

Carcinoid tumors

Question 268

which form of carcinoid is more likely to grow in a disorganized fashion and invade lymphatics with dense-core granules characteristic of other neuroendocrine tumors with serotonin, neuron-specific enolase, boobesin, calcitonin and other

Answer 268

Atypical carcinoid

Question 269

What are some salient clinical features of carcinoid tumors?

Answer 269

- cough, hemopytsis, impaired drainage, bronchietasis, emphysema and atelectasis - capable of producing class carcinoid syndrome with attacks of diarrhea, flushing and cyanosis. - Most do not metastasize thus amenable to resection - 95% 5yr survival

Question 270

Lung hamartoma, most commonly containing cartilage, is associated with chromosomal aberration involving _ or _

Answer 270

6p21 or 12q14-q15

Question 271

_ primarily affects young women of childbearing age (probably related to estrogen), characterized by proliferation of perivascular epitheloid cells that express markers of both melanocytes and smooth muscle cells.

Answer 271

Lymphagioleiomyomatosis

Question 272

Lymphogioleiomyomatosis is commonly associated with loss of function mutation in _

Answer 272

tumor suppressor TSC2 (encodes tuberin), negative regulator of mTOR, a key regulator cellular metabolism

Question 273

how to lymphagioleiomyomatosis pt present clinically?

Answer 273

- dyspnea or spontaneous pneumothorax with emphysematous changes. - slow growing over several decades

Question 274

what gene mutation is implicated in inflammatory myofibroblastic tumor and what age group does it affect commonly?

Answer 274

ALK gene located on 2p23 - affects kids - presents with fever, cough, chest pain, hemoptysis - image shows: usually single, round, well defined, peripheral mas with calcium deposit graish white in color.

Question 275

what gene mutation is implicated in inflammatory myofibroblastic tumor and what age group does it affect commonly?

Answer 275

ALK gene located on 2p23 - affects kids - presents with fever, cough, chest pain, hemoptysis - image shows: usually single, round, well defined, peripheral mas with calcium deposit grayish white in color.

Question 276

A 68-year-old male is diagnosed with squamous cell carcinoma in the upper lobe of his right lung. A chest radiograph can be seen in image large coin shaped lesion at the apex of the right lung. Which of the following would you most expect to find in this patient? 1. Polydipsia 2. Digital clubbing 3. Superior vena cava syndrome 4. Anisocoria 5. Lateral gaze palsy

Answer 276

4. Anisocoria Pt has pancoast's tumor. A Pancoast tumor is a lung cancer located in the apex of the lung. Pancoast tumors are classically associated with ipsilateral Horner's syndrome: ptosis (eyelid droop), miosis (pinpoint pupil), and anhydrosis (lack of sweating).

Question 277

Pleural effusion are commonly either inflammatory or noninflammatory. What are common causes of inflammatory?

Answer 277

"pleuritis" - TB, pneumonia, abscess, radiation, uremia. - presents as empyema (yellow green, local, creamy push with lots of neutrophils); or hemorrhagic pleuritis

Question 278

What are some common noninflammatory pleural effusions?

Answer 278

- hydrothorax (associated with CHF, found in base with upright) - Chylothorax = milky fluid of lymph, fat due to lymph obstruction - hemothorax (ruptured aorta, penetrating truma - Pneumothorax = air (spontanous idiopathic pneumo seen in young adults that rupture a bulla into subq tissue; tension pneumo = tissue act as a valve flap allowing air into pleural space on inflation but not back out- associated with great vessel occluded leading to hypotension and mediastinal shift away from injured lung)

Question 279

Metastasis from the lung common goes to _.

Answer 279

brain, liver, but LOVE adrenal glands. Mets to the lungs can come from anywhere

Question 280

these tumors are 1-2cm mass on the pleural surface that shows whorls of reticulin and collagen fibers and are positive for CD34+ and keratin-negative by immunostatining.

Answer 280

Solitary fibrous tumor. Associated with cryptic inversion of chromosome 12 involving genes NAB2 and STAB6 rearrangement creating a NAB2-STAT6 fusion gene --> chimeric transcription factor

Question 281

Mesothelioma is associated with homozygous deletion of _

Answer 281

tumor suppressor gene CDKN2A/NK4a. | visualized using FISH to see chromosome 9p

Question 282

What are the three types of mesothelioma and what are their salient features?

Answer 282

1. Epitheloid (marker positive: keratin proteins, calretinin, Wilm's tumor 1, cytokeratin 5/6 and D2-40) 2. Sarcomatoid: resembles spindle cell sarcoma , resembling fibrosarcoma. 3. Mixed type (biphasic) contains both epitheloid and sarcomatoid patterns

Question 283

what are the common offenders of infectious rhinitis?

Answer 283

adenoviruses, echoviruses, and rhinovirus

Question 284

How does infectious rhinitis usually present?

Answer 284

- acute - 98% caused by virus - initial phase: nasal mucosa is thickened, edematous, and red; nasal cavities are narrowed turbinates are enlarged. - secondary bacterial infection can enhance the inflammatory reaction and produce mucoprulent or suppurative exudate - nasal congestion, mucopurulent nasal discharge, pain and pressure, headache, olfactory disturbance, post nasal drainage, cough

Question 285

how does allergic rhinitis present?

Answer 285

- IgE-mediated - seasonal - perennial: rxn to perennial aeroallergens including dust mites, mold, animal dander, pollen - episodic

Question 286

Nasal polyps is due to recurrent attacks of _.

Answer 286

rhinitis

Question 287

what are nasal polyps composed of?

Answer 287

hyperplastic or cystic mucous glands, infiltrated with a variety of inflammatory cells, including neutrophils, eosinophils and plasma cells with occasional clusters of lymphocytes In the absence of infection, the mucosal covering is intact, but with chronicity it may become infected and ulcerated

Question 288

In chronic rhinitis, what contributes to the bacterial infection?

Answer 288

a deviated nasal septum or nasal polyps with impaired drainage of secretion

Question 289

A 15-year-old boy presents to with clear fluid discharge from his nose for 2 days duration. This has also been associated with sneezing. On nasal exam, the mucosa and turbinates appear edematous and slightly bluish. what is the most likely diagnosis?

Answer 289

Allergic rhinitis

Question 290

While acute sinusitis is most commonly preceded by acute or chronic rhinitis, maxillary sinusitis occasionally arises by extension of _

Answer 290

periapical infection through the bony floor of sinus, offending agents are usually those found in oral cavity

Question 291

what are the risk factors for sinusitis?

Answer 291

- kartagener's disasee - cystic fibrosis - wegener's granulomatsis - smoking

Question 292

A 4-year-old boy is noted by his pediatrician to have recurrent respiratory infections. If this child was born with a genetic defect in ciliary function, which of the following could be seen as part of his presentation and work-up? 1. Abnormally concentrated sweat on sweat testing 2. A saddle nose deformity on physical exam 3. A right-sided cardiac silhouette on chest radiograph 4. A history of Hirschprung’s disease 5. A history of delayed umbilical separation

Answer 292

3. A right-sided cardiac silhouette on chest radiograph The child in this vignette most likely has Kartagener’s syndrome, characterized by a hereditary defect in ciliary function. This condition also presents with dextrocardia (a heart on the right side).

Question 293

_ is infection of paranasal sinus due to undrained collection of pus

Answer 293

sinusitis. Maxilary sinuses are commonly involved. | - can be bacterial or fungal

Question 294

Acute sinusitis is sinusitis with a sudden onset that lasts less than a month and most commonly caused by what _

Answer 294

- s. pneumoniae - H. influenzae - Moraxella cattarhalis

Question 295

necrotizing ulcerating lesion of the nose and URT may be produced by _

Answer 295

1. acute fungal infection such as mucormycosis (esp in diabetics and immunocmpromised). pts will present with sudden onset of nose bleed, ulcerated nasal mucosa, proptosis and periorbital edema 2. Granulomatosis with polyangiitis 3. Extranodal NK/T cell lymphoma, nasal type in which tumor cells harbar EBV

Question 296

what are the common causative agents of pharyngitis and tonsilitis?

Answer 296

viral upper respiratory infections commonly imlicated are rhinoviruses, echoviruses, adenoviruses and less commonly RSV. Bacterial infection may be superimposed on these viral infection or can be primary. Most common are beta hemolytic strep but s. aureus is also implicated

Question 297

_ is a benign,highly vascular tumor that occurs almost exclusively in adolescent males who are often fair-skinned and red headed. Has an association with familial adenomatous polyps. Treated with surgery but can recur

Answer 297

nasopharyngeal angiofibroma

Question 298

_ is a benign neoplasm seen in males 30-60, arising from respiratory or schneiderian mucosa lining the nasal cavity and paranasal sinuses and comes in three flavors: exophytic (most common), endophytic, and cylindrical.

Answer 298

Sinunasal (Schneiderian papilloma.

Question 299

What virus has been implicated in exophytic and endophytic sinonasal papilloma?

Answer 299

HPV types 6 and 11

Question 300

which form of sinonasal papilloma is locally aggressive with papillomatous proliferation of squamous epithelium that invaginates underlying storma. Has high rates of recurrence if not adequately excised and can have serious complications such as invasion of orbit or cranial vault. 10% can undergo malignant transformation

Answer 300

Exophytic

Question 301

Olfactory neuroblastoma arises from where?

Answer 301

neuroectodermal olfactory cells within the mucosa, particularly superior aspect of nasal cavity. These are the same small, blue, round cells seen in many other neoplasms such as lymphoma, small cell carcinoma, and etc.

Question 302

what markers can be used to test for olfactory neuroblastoma?

Answer 302

Because it's neuroendocrine in origin, you can use enolase, synaptophysin, CD56, and chromogranin

Question 303

Often mistaken for squamous cell carcinoma, this carcinoma can occur in nasopharynx, salivary gland, or midline structures in thorax or abd. It is extremely aggressive and resistant to conventional therapy--most survive less than a yr.

Answer 303

NUT midline carcinoma

Question 304

What genetic abnormality gives rise to NUT midline carcinoma?

Answer 304

translocation that create fusion genes encoding chimeric proteins coprised of most of NUT, a chromatin regulator and a protein of a chromatin reader protein usually BRD4.

Question 305

Keratinizing squamous cell carcinoma, nonkeratinzing squamous cell carcinoma and undifferentiated/basoloid carcinomas are the three patterns of what carcinoma?

Answer 305

nasopharyngeal carcinoma

Question 306

what three factors influence the origin of nasopharyngeal carcinoma?

Answer 306

1. heredity 2. age 3. infection with EBV Common in pats of Africa as most frequent childhood cancer. Also seen Chinese adults.

Question 307

which form of nasopharyngeal carcinoma has the best progonosis and the worst prognosis

Answer 307

Best: nonkeratizing type Worse: keratinizing type

Question 308

causes of laryngitis

Answer 308

- alleric, - - viral - bacterial - chemical insults - smoking - GERD - systemic infections such as TB and diphtheria

Question 309

what is croup?

Answer 309

laryngotracheobronchitis in kids in which inflammatory narrowing of the airway produces the inspiratory stridor so frightening to parents. Most common cause is parainfluenza virus

Question 310

what is vocal cord nodule caused by?

Answer 310

excessive cause, usually bilateral. - composed of degenerative (myxoid) connective tissue - pt presents with hoarseness, resolves with rest

Question 311

_ are benign neoplasms, usually located on true vocal cords, that form soft, respberry like prolifeation rarely more than 1cm in diameter. On histo multiple slender, finger like projection supported by central fibrovascular cores covered by stratified squamous epithelium. Ulceration can occur accompanied by hemoptysis

Answer 311

Squamous papilloma and papillomatosis

Question 312

How does juvenile laryngeal papillomatosis differ from adult form?

Answer 312

papillomas are usually single in adults but are often multiple in kids.

Question 313

what is the common causative agent of squamous papilloma and papillomatosis?

Answer 313

HPV 6 and 11. | Don't usually become malignant but do recur

Question 314

what sequence of alterations are seen in the larynx related to carcinoma of larynx?

Answer 314

- hyperplasia, atypical hyperplasia, and dysplasia - carcinoma in situ - carcinoma

Question 315

what are the risk factors of carcinoma of the larynx?

Answer 315

- smoking - alcohol - nutritional factors - asbestos - irradiation - infection with HPV

Question 316

what do the laryngeal carcinoma arise from? how do they look?

Answer 316

squamous epithelial lining of vocal cord. - typically in men in 50s, smoker - dysplastic sq epithelium, fungating bulky, mass protruding from laryngeal surface often w/ ulceration

Question 317

a 25-year-old male, shot in the right lower chest and has been stable for the past two hours. He has been getting progressively more short of breath. Vitals reveal temperature 37 degrees Celsius, heart rate of 121, blood pressure of 100/70, respiratory rate 23, and oxygen saturation of 89% on room air. You hear diminished breath sounds on the right side. His oxygen saturation is dropping. A bedside x-ray is taken and reveals the following pneumothorax with trachea deviated away from the pneumothorax. What is the next step in management? 1. Insert a chest tube 2. Place the patient on oxygen and insert a chest tube 3. Perform a needle thoracostomy 4. Obtain an arterial blood gas 5. Perform a thoracotomy

Answer 317

3. Perform a needle thoracostomy Pt has tension pneumothorax due to the trauma.

Question 318

An AIDS pts presents with symptoms of pneumonia. Cryptosporidium parvum are found in stool specimen. Bronchoalveolar lavage is performed and shows pink, foamy exudate with little inflammation. which additional findings on microscopic exam is most likely to have in BAL specimen?

Answer 318

Multiple cysts with GMS stain. Pneumocystis jiroveci pneumonia is associated with AIDS. PCP infection produces an exudate composed of pneumocystis cysts and trophozoites with little accompanying inflammation.