The Lung Flashcards

Question

Surfactant defiency issue

Answer 1

Infants need the surfactant to properly inhale with less effort, but if they don’t have any then each progressive breath the lungs collapse a little more This problem of stiff atelectatic lungs is compounded by a soft thoracic wallet hat is pulled in as the diaphragm descends

Answer 2

Protein rich, fibrin rich exudation into the alveolar spaces with the formation of hyaline membranes - fibrin hyaline membranes are barriers to gas exchange->CO2 retention and hypoxemia - hypoxemia impairs further surfactant synthesis Hypoventilation !!!

Answer 3

Acidosis and pulmonary vasoconstriction (from the relative hypoxia) leading to pulmonary hypoperfusion causing tissue damage and plasma leak into the alveoli Ultimately there are necrotic cells and fibrin deposition with a hyaline membrane being laid down and exacerbating the problem in a viscous cycle

Answer 4

Produced by type II pneumocytes Modulated by cortisol (glucocorticoids most important*), prolactin, thyroxine, and TGFB

Answer 5

Intrauterine stress and FGR Corticosteroid

Answer 6

Increased glucose in mother leads to increased insulin in fetuses. Increased insulin in fetus inhibits synthesis of surfactant by way of inhibiting the steroids leading to a greater risk of RDS - infants of diabetic mom have higher risk of developing RDS - treat with corticosteroid therapy

Answer 7

Corticosteroid therapy

Answer 8

Labor increases surfactant synthesis

Answer 9

Increases risk of RDS C section is less stressful for baby and labor increases surfactant

Answer 10

Lungs are normal size, solid airless, and reddish purple in color Alveoli are poorly developed and collapsed—atelectasis Necrotic cells (including type II pneumocytes) can be seen early and later they are incorporated within eosinophilic hyaline membranes that are also composed of fibrin NEVER seen in stillborn Infants that survive more than 48 hours will have reparative changes int he lungs where the alveolar epithelium proliferated under the surface of the membrane and detach into the airspace where is digested by macrophages

Answer 11

Clinical course and prognosis depends on the maturity and birth weight of the infant and the promptness of institution of therapy (administration of surfactant: poractant Alfa, bear tang, calfactant) Best thing to do is delay labor long enough to reach maturity or induce maturation of the lungs

Answer 12

Sample the phospholipids in the amniotic fluid - phosphatidylcholine is important for surfactant - measure a lecithin: phosphatidylcholine ratio; want it to be greater than 2:1?

Answer 13

Retrolental fibroplasia Bronchopulmonary dysplasia

Answer 14

Phase I: hyperoxaluria; expression of VEGF is decreased and causing endothelial cell apoptosis Phase II:VEGF levels rebound after return to relatively hypoxic room air -induced retinal vessel proliferation (neovascularization) that is characteristic of the retina lesions

Answer 15

Major abnormality: striking decrease in alveolar septation (manifested as large, simplified alveolar structures) and a dysmorphic capillary configuration caused by a potentially reversible impairment in the development of alveolar septation at the "saccular stage" Multiple factors: hyperoxemia, hyperventilation, prematurity, inflammatory cytokines (TNF, IL-1, IL-6, and IL-8), and vascular maldevelopment

Answer 16

PDA, intraventricular hemorrhage, necrotizing enterocolitis

Answer 17

Incomplete expansion of the lungs (neonatal atelectasis) or collapse of previously inflated lung producing areas of relatively airless pulmonary parenchyma Can reduce oxygenation and predispose to infection Reversible (except in contraction)

Answer 18

Complete airway obstruction air is resorbed from the dependent alveoli which then collapse Mediastinum shifts towards the affected lung because lung volume is diminished most often caused by excessive secretions (mucus plug) or exudates within smaller bronchi as may occur in bronchial asthma, chronic bronchitis, bronchiectasis, or post-operative setting Can also be due to aspiration or tumor fragments

Answer 19

occur whenever significant volumes of fluid accumulate within the pleural cavity Transudate (hydrothorax), exudate (pleural effusion), blood (hemothorax), air (pneumothorax), tumor Effusion from cardiac failure/neoplasm Blood from aneurysm rupture Mediastinum shifts away from the affected lung

Answer 20

focal or generalized pulmonary or pleural fibrosis prevent full expansion Mediastinum can shift toward the affected lung if it is ipsilateral, no change if it is bilateral Irreversible

Answer 21

leakage of excessive interstitial fluid in alveolar spaces due to: Increased hydrostatic pressure Increased capillary permeability Leads to heavy, wet lungs regardless of etiology Decreased oxygenation -- diffusion barrier is increased --> cyanosis, dyspnea, low O2 sat Predisposes patient to infection Therapy and outcome depend on the etiology

Answer 22

Engorged alveolar capillaries due to increased hydrostatic pressure, often a result of left-sided heart failure Fluid accumulation occurs in basal regions of lower lungs first (dependent edema) Granular, pink precipitates in the alveolar spaces Chronically leads to brown, firm lungs (brown induration) due to interstitial fibrosis and hemosiderin laden macrophages (pathognomonic "heart failure cells")

Answer 23

due to injury of the alveolar septa inflammatory exudate that leaks into the interstitial space and, in more severe cases, the alveoli in most forms of pneumonia, the edema remains localized and is overshadowed by the manifestations of infection If diffuse/severe can lead to Acute Respiratory Distress Syndrome (ARDS)

Answer 24

Abrupt onset of hypoxemia and bilateral pulmonary infiltrates in the absence of heart failure Increased pulmonary vascular permeability due to epithelial cell death ARDS is a manifestation of severe ALI/DAD ARDS and ALI are associated with inflammation-associated increases in pulmonary vascular permeability, edema, and epithelial cell death histologically, this is recognized as diffuse alveolar damage (DAD) due to localized or systemic insult Sepsis, diffuse pulmonary edema, gastric aspiration, and trauma account for more than 50% of the cases Worse prognosis in smokers and alcoholics pathogenesis is a "viscous cycle of increasing inflammation and pulmonary damage

Answer 25

Severe ALI/DAD

Answer 26

There is injury to pneumocyte injury that is recognized by resident macrophages ("dust cells") Can also be activated by systemic factors in times of sepsis Then there is increased endothelial permeability and adhesion molecules There are also increased production and secretion of procoagulant proteins and chemokines

Answer 27

neutrophils come in and degranulate --> release inflammatory mediators including proteases, reactive oxygen species, and cytokines macrophage inhibitory factor (MIF) helps to sustain the pro-inflammatory response result: increased recruitment and adhesion of leukocytes --> more endothelial injury --> local thrombosis this cycle of inflammation and endothelial damage lies at the heart of ALI/ARDS

Answer 28

The alveolar caps become leaky and allow the edema to come in Type II pneumocytes are damaged which results in surfactant-related issues (i.e. gas exchange becomes worse --> shortness of breath) The protein-rich fluid and dead epithelial cells then forms in hyaline membranes (characteristic of ALI/ARDS

Answer 29

Impeded due to epithelial necrosis and inflammatory damage that impairs edema resorption Eventually, if the inflammation lessens then the macrophages can clean everything up and heal the damaged areas with fibrogenic factors (i.e. TGF-β and PDGF) There is then fibrosis of the alveolar walls and bronchiolar stem cell replacement of pneumocytes Type II Pneumocytes replace the pneumocytes, act as stem cells

Answer 30

Lungs are diffusely firm, red, boggy and heavy (hyperemic and congested?) Congestion with interstitial and intraalveolar edema, inflammation, fibrin deposition, and diffuse alveolar damage Lined with hyaline membranes (composed of necrotic epithelial debris and exuded proteins) morphologically similar to those seen in hyaline membrane diseases of neonates alveolar hyaline membranes consist of fibrin-rich edema fluid mixed with the cytoplasmic and lipid remnants of necrotic epithelial cells (protein-rich exudate) Characteristic histologic picture of ARDS is that of hyaline membranes lining alveolar walls. Edema, scattered neutrophils and macrophages, and epithelial necrosis are also present

Answer 31

Type II pneumocyte proliferation Granulation tissue forms in the alveolar walls as a response to the hyaline membranes most cases: granulation tissue resolves and leaves only minimal functional impairment can progress to interstitial fibrosis with severe scarring Superimposed bronchopneumonia can be fatal

Answer 32

LI/ARDS: Clinical ALI or ARDS patients are usually already admitted for one of the predisposing conditions (e.g. sepsis, severe head trauma) Dyspnea and tachypnea are characteristic --> cyanosis, hypoxemia, respiratory failure, and the appearance of diffuse bilateral infiltrates follow hypoxemia may be refractory to oxygen therapy due to ventilation/perfusion mismatching Respiratory acidosis can develop (can't blow off CO2 as effectively --> buildup of CO2 --> acidosis) Stiff lungs from the lack of surfactant can develop early in the course Functional abnormalities are not evenly distributed Poorly aerated regions are still perfused = V/Q mismatch & hypoxemia Ventilation is occurring, but there in not as much perfusion as expected

Answer 33

40% secondary to sepsis of multi organ failrue

Answer 34

Mechanical ventilation while treating the underlying cause no proven specific treatments -- treatment of the underlying cause has improved Most patients will recover, but many of them can still have physical and cognitive impairment most deaths are attributable to sepsis or multiorgan failure and, in some cases, direct lung injury In minority of cases, exudate and diffuse tissue destruction --> scarring, interstitial fibrosis, and chronic pulmonary disease

Answer 35

Widespread ALI of unknown etiology with a rapidly progressive clinical course Present with acute respiratory failure within 3 weeks of URI Imaging/pathology identical to organizing ALI Average age: 59; No gender preference 33-74% mortality, typically in first 12 months Morphology is the same as the organizing stage of ALI Progresses rapidly with most deaths occurring in 1-2 months Survivors are prone to recurrence and chronic interstitial disease

Answer 36

Increased resistance to airflow due to partial or complete obstruction at any level Decreased maximal flow rates during forced expiration FEV1 / FVC < 0.8

Answer 37

Decreased expansion of the lung parenchyma and decreased total lung capacity Chest wall disorders (e.g. severe obesity, pleural diseases, kyphoscoliosis, and poliomyelitis) Chronic interstitial and infiltrative disease (e.g. pneumoconioses and interstitial fibrosis) Proportionate Decreased in lung capacity and FEV1 --> FEV1 / FVC is normal

Answer 38

Severe obesity, pleural diseases, kyphoscoliosis, and poliomyelitis

Answer 39

Pneumoconiosis and infiltrative disease

Answer 40

COPD(emphysema, chronic bronchitis) Asthma Bronchiectasis

Answer 41

Anatomical site-bronchus Major pathological changes-mucous gland hyperplasia, hypersecretion Etiology:tobacco smoke, air pollutants Signs and symptoms :fought sputum production

Answer 42

An atomic site: bronchi Major pathology changes: airway dilation and scarring Etiology: persistent or severe necrotizing infections Signs and symptoms: cough, pursuant sputum, fever

Answer 43

Anatomic site: bronchus Major pathological changes: smooth msucle hyperplasia, excess mucus, inflammation Etiology: immunologic or unknown; drug induced Signs and symptoms: episodic wheezing, cough, dyspnea

Answer 44

Anatomic site: acinus Major pathological changes: airspace enlargement, wall destruction->blebs Etiology: tobacco smoke: highly Signs and symptoms: dyspnea

Answer 45

Can be seen with any form of obstructive disease or as an isolated finding: contributes to obstruction both in emphysema and chronic bronchitis

Answer 46

Asthma == reversible bronchospasm chronic bronchitis and emphysema == irreversible bronchospasm *Generally

Answer 47

C ommonly includes emphysema and chronic bronchitis Increased risk: Cigarette smoking, female, African American, environmental/occupational pollutants, airway hyperresponsiveness, genetic polymorphisms

Answer 48

I rreversible enlargement of airspaces distal to the terminal bronchioles Alveolar wall destruction without obvious fibrosis, except in the small airways Classified by anatomic distribution within the lobule -- centriacinar*, panacinar*, paraseptal, and irregular lobule == cluster of acini (terminal respiratory units) *only the first two cause clinically significant airflow obstruction

Answer 49

Destruction and enlargement of the central or proximal parts of the acini, formed by respiratory bronchioles, sparing distal alveoli Emphysematous and normal airspaces exist within the same acinus and lobule Predominantly upper lobes and apices When severe, the distal acini may be involved (difficult to distinguish against panacinar emphysema) *Heavy smokers* and often associated with chronic bronchitis (COPD) Most common form of emphysema 95% of cases

Answer 50

Upper lobes and spices Smokers

Answer 51

Centriacinar emphysema

Answer 52

Uniform destruction and enlargement of the entire acini from the level of the respiratory bronchiole to the terminal blind alveoli Common in the lower zones and anterior margins of the lung Most severe at the lung bases Associated with α1-antitrypsin deficiency

Answer 53

Proximal acinus is normal; distal acinus is predominantly affected Prominent near the pleura, along septa and lobules and occurs adjacent to fibrosis/scarring/atelectasis More severe in the upper half of the lungs Multiple, continuous, enlarged airspaces that may sometimes form cyst-like structures -- "blebs" Commonly the underlying lesion in spontaneous pneumothorax in the young

Answer 54

Acinus is irregularly involved Invariable associated with scaring Clinically insignificant

Answer 55

parenchymal destruction == emphysema | airway disease == bronchiolitis and chronic bronchitis

Answer 56

Increased levels in the affected areas -- leukotriene B4, IL-8, TBF, and others Released by resident epithelial cells and macrophages Attract inflammatory cells from circulation (chemotaxis) Amplify inflammation (cytokines) Induce structural changes (GFs)

Answer 57

connective tissue is broken down by enzymes released from the inflammatory and epithelial cells Loss of elastic tissue = respiratory bronchiole collapse during expiration causing functional obstruction Deficiency of antiproteases (may be genetic) is common in patients with emphysema α1-antitrypsin == anti-protease; deficiency upsets the balance --> panlobular emphysema trypsin is a protease; anti-trypsin is an anti-protease -- don't get fucked up on words

Answer 58

Oxidants are produced by tobacco smoke, from alveolar damage, and from inflammatory cells NFR2 inactivation: significantly increased sensitivity to tobacco smoke NFR2 is a sensor for oxidants in alveolar epithelial cells Activated by intracellular oxidants to upregulate genes that protect from oxidant damage NFR2 == transcription factor that upregulates expression of multiple genes that protect cells from oxidant damage

Answer 59

Thought to exacerbate the associated inflammation and chronic bronchitis

Answer 60

Found in 1% of all patients anti-protease: protects against proteases, especially elastase (released by neutrophils) Much more likely to cause emphysema, especially if the patient smokes Encoded on the Pi locus of chromosome 14 patients with the Z allele have decreased serum levels and 80% of homozygotes (piZZ) will develop symptomatic panacinar emphysema which is even more accelerated and severe if the patient smokes

Answer 61

Some genetic variants of the receptor can lead to an increased risk for the disease Makes smoking more addictive and thus increases the risk of the disease smoke more and smoking is even worse for you

Answer 62

small airways are normally held open by the elastic recoil of the lung parenchyma loss of elastic tissue in the walls of alveoli that surround respiratory bronchioles reduces radial traction and thus causes the respiratory bronchioles to collapse during expiration --> functional airflow obstruction

Answer 63

goblet cell hyperplasia and mucus plugging of the lumen inflammatory infiltrates in bronchial walls -- neutrophils, macrophages, B-cells, and T-cells bronchiolar wall thickening due to fibrosis and smooth muscle hypertrophy --> increased airway obstruction

Answer 64

Diffuse disease: voluminous lungs that overlap the heart Alveolar wall rupture can produce huge airspaces (blebs and bullae) that are more commonly found in the upper 2/3 of the lungs that compresses the bronchioles and vasculature Alveolar spaces are enlarged and separated by thin septa with only focal centriacinar fibrosis The Pores of Kohn are large and look to be clubbed shape and protrude blindly into the alveolar spaces Septal capillaries are compressed and bloodless

Answer 65

Dyspnea, wheezing, cough begin to occur when 1/3 of pulmonary parenchyma is lost Cough and expectorant are very variable and depend on the level of the associated bronchitis Severe weight loss (confused with occult cancer) Barrel chested, dyspneic, hunched over, breathes through pursed lips impaired expiratory airflow (best measured through spirometry) is the key to diagnosis 'Pink puffers' well oxygenated at rest due to overventilation chronic bronchitis == blue bloaters emphysema == pink puffers

Answer 66

Development of cor pulmonale is a poor prognostic factor Death due to: Coronary Artery Disease Respiratory Failure Right Heart Failure Massive collapse of lungs 2° to pneumothorax

Answer 67

Smoking cessation O2 therapy Long acting bronchodilators (tiotropiums and ipratropium) with inhaled corticosteroids physical therapy Bullectomy Lung volume reduction surgery (select patients) Lung transplant (select patients) α1-antitrypsin replacement therapy is currently being evaluated

Answer 68

Associated with lung overinflation or focal emphysematous change

Answer 69

Dilation of alveoli in response to loss of lung parenchyma elsewhere hyper-expansion of residual lung parenchyma following surgical removal of diseased lung or lobe

Answer 70

Foreign body (tumor, foreign object) creates a subtotal obstruction -- the lung expands because air is trapped Congenital Lobar Overinflation in infants due to hypoplasia of bronchial cartilage sometimes associated with other congenital cardiac and lung abnormalities Overinflation in Obstructive Lesions Ball-valve phenomenon which admits air on inspiration but traps it on expiration Collaterals introduce air behind the obstruction pores of Kohn canals of Lambert (bronchioalveolar connections) Can be life-threatening as the affected lung can compress the remaining lung

Answer 71

Large sub-pleural bullae or blebs that can occur with any type of emphysema Bullae: spaces of air that are greater than 1cm Occurs near the apex Often near old tuberculous scarring Rupture can cause pneumothorax

Answer 72

Entry of air into connective tissue of the lung, mediastinum, or subcutaneous tissue In most cases is due to alveolar tears in pulmonary emphysema allowing air to enter the stroma of the lungs, but can also be due to chest wound or fractured rib rapid increases in pressure within the alveolar sacs (e.g. coughing with bronchiolar obstruction) premature infants on positive pressure ventilation are most at risk Artificially ventilated adults

Answer 73

Persistent cough with sputum production for at least three months in at least two consecutive years in the absence of other identifiable causes Can accelerate decline in lung function, cause cor pulmonale and HF or atypical metaplasia of respiratory epithelium (fertile grounds for cancerous transformation) Common in smokers and smog-laden cities COPD spectrum == emphysema to chronic bronchitis most patients have features of both associate Reid Index with Chronic Bronchitis

Answer 74

Predominantly due to chronic irritation from inhaled substances/irritants such as tobacco smoke (90% of patients also smoke) and also dust from grain, silica, or cotton earliest feature == hypersecretion of mucus in the large airways associated with hypertrophy of the submucosal glands in the trachea and bronchi With time there is increased numbers of goblet cells in the smaller airways too Chronic inflammation leads to fibrosis and obstruction of the small airways Exacerbated by 2° infections Smoking inhibits cilia to prevent the clearing of mucous and thus increased risk of infection

Answer 75

Hyperemia (excessive blood vessels) Edema of lung mucous membranes mild chronic inflammation of the airways (predominantly lymphocytes) and enlargement of the mucus-secreting glands of the trachea and bronchi -- characteristic features of chronic bronchitis Mucinous secretions filling airways Mucous gland hyperplasia hyperplasia == increase in size Reid Index == ratio of the thickness of the mucous gland layer to the thickness of the wall between the epithelium and the cartilage Normally is .4 or 40%; increased in chronic bronchitis in proportion to the severity and duration associate Reid Index with chronic bronchitis -- just the glandular component don't use the Reid Index for asthma Bronchiolar inflammation, fibrosis, and gland hyperplasia leads to airway obstruction Bronchial epithelium may exhibit squamous metaplasia + dysplasia There is marked narrowing of bronchioles caused by mucus plugging, inflammation, and fibrosis Severe: bronchiolitis obliterans (fibrosis causes obliteration of the lumen in severe cases

Answer 76

y Persistent cough productive of sparse sputum for at least three consecutive months in at least two consecutive years eventually, dyspnea on exertion develops hypercapnia (retain CO2), hypoxemia and mild cyanosis over time -- "blue bloaters" chronic bronchitis == blue bloaters emphysema == pink puffers Can lead to cor pulmonale and heart failure Death is possible from further impairment of respiratory function due to superimposed acute infections

Answer 77

disorder of the conducting airways episodic reversible bronchospasm due to smooth muscle hyperreactivity, inflammation of the bronchial walls, and increased mucus production Leads to cough, wheeze, chest tightness, and breathlessness, especially at night and in the morning

Answer 78

Atopic (most common0 | Nonatopic

Answer 79

Classic IgE-mediated (Type I) hypersensitivity reaction triggered by environmental allergens (e.g. pollen, food) that is synergistically triggered by other proinflammatory things in the environment and viral infections

Answer 80

Associated with TH2 helper T cell mediated inflammation and responds well to treatment with corticosteroids

Answer 81

Family history common

Answer 82

Immediate wheal and far reaction to the antigen they are sensitized to

Answer 83

Levels of allergen sensitization shown by RAST which can detect the presence of IgE antibodies that are specific for individual allergens

Answer 84

No evidence of allergen sensitization Negative skin test Genetic involvement less common viral respiratory infections are common triggers, as well as inhaled air pollutants (smoking, sulfur dioxide, ozone, and nitrogen dioxide == smog) that can cause chronic airway inflammation and hyperreactivity ozone has no pathologic effects; it is only an irritant Can even be caused by cold or exercise

Answer 85

Aspirin sensitive asthma == uncommon; occurs in individuals with recurrent rhinitis and nasal polyps exquisitely sensitive to small doses of aspirin and other NSAIDs asthmatic attacks + urticaria (hives) Inhibition of COX pathway --> decreased PGE2 --> increase in pro-inflammatory leukotrienes NSAIDs More likely to occur in individuals with recurrent rhinitis and nasal polyps

Answer 86

Minute quantities of chemicals induces signs and symptoms after repeated exposure Varying underlying mechanisms

Answer 87

Seen in smokers

Answer 88

TH2 hyperreactivity leads to: IL-4: production of IgE -- "5Always and 4Ever" IL-5: activates eosinophils IL-13: stimulates bronchial submucosal glands to secrete mucous and B-cells to make more IgE Antigen binding to IgE coated mast cells causes primary and secondary mediator release that cause: T-lymphocytes and epithelial cells secrete chemokines that recruit more T-lymphocytes and eosinophils and exacerbate the problem

Answer 89

Bronchoconstriction triggered by direct stimulation of subepithelial vagal (parasympathetic) receptors through both central and local reflexes increased mucus production variable degrees of vasodilation increased vascular permeability

Answer 90

dominated by the recruitment of leukocytes, notably eosinophils, neutrophils, and more T-cells Persistent bronchospasm and edema Leukocytic infiltration Epithelial damage and loss Repeated bouts lead to airway remodeling -- asthma == airway remodeling Hypertrophy and hyperplasia of bronchial smooth muscle and mucus glands Increased vascularity Increased deposition of subepithelial collagen TH2 is the dominant cell type TH17 T-cells are also present and they are the ones that recruit neutrophils down regulation of IL-17 == cold abscesses

Answer 91

Leukotrienes C4, D4, E4 Acetylcholine

Answer 92

Prolonged bronchoconstriction, vascular permeability, and mucus secretion

Answer 93

Stimulation of muscarinic receptors causing airway smooth muscle constriction

Answer 94

``` Histamine PGD2 PAF Cytokines and chemokines ^might prove important in certain types of chronic or non allergic asthma ```

Answer 95

Bronchoconstrictor

Answer 96

Bronchoconstriction and vasodilation

Answer 97

Patients with atopic asthma are more likely to have other allergic disorders like allergic rhinitis and eczema Implicated genes can affect 1° or 2° immune responses, tissue remodeling or the patients response to therapy

Answer 98

Polymorphism in the IL13 gene have the strongest and most consistent association with asthma

Answer 99

``` IL4R HLA class II ``` ADAM33 leads to bronchial smooth muscle and fibroblast proliferation B2-adrenergic receptor (airway reactivity) YKL-40: increased levels of the China tase-like glycoproteins is directly correlated with disease severity , airway remodeling, and decreased pulmonary function

Answer 100

City Living -- there are many airborne pollutants that may initiate the TH2 response; city life limits the exposure of very young children to certain antigens infections themselves are not a cause of asthma young children with aeroallergen sensitization who develop lower respiratory tract viral infections (rhinovirus type C, respiratory syncytial virus) have 10-30x increased risk of developing persistent and/or severe asthma viral and bacterial infections are associated with acute exacerbations of the disease airway remodeling = structural changes in the bronchial wall brought on as a result of repeated bouts of allergen exposure and immune reactions; irreversible component hypertrophy and hyperplasia of bronchial smooth muscle epithelial injury increased airway vascularity increased subepithelial mucus gland hypertrophy deposition of subepithelial collagen

Answer 101

The following is especially found in patients with status asthmaticus Overinflated lungs with patchy atelectasis Mucus plugging of airways that also contains shed epithelium Whorled mucus plugs (Curschmann spirals) Microscopic lung edema, with eosinophils and Charcot-Leyden crystals (eosinophilic protein galectin-10) Airway remodeling == irreversible component; this is seen in asthma Thickening of airway wall Subbasement membrane fibrosis (deposited I and III collagen) Increased vascularity Bronchial wall smooth muscle and mucosal gland hypertrophy

Answer 102

``` Attacks can be hours long Chest tightness Prolonged expiration Peripheral blood eosinophilia Wheezing Dyspnea Cough **atopic dermatitis**: rash on flexural surfaces asthma == eosinophils, IL-5, Curschmann spirals, Charcot-Leyden crystals ```

Answer 103

Severe form of asthma where the paroxysm persists for days and weeks Airflow obstruction may be so severe it causes cyanosis or death

Answer 104

About half of the cases will remit, but lots of cases will return in adulthood

Answer 105

Destruction of smooth muscle and elastic tissue by chronic necrotizing infections that leads to permanent dilation of bronchi and bronchioles becoming less common due to infection control

Answer 106

Congenital or hereditary conditions like cystic fibrosis and primary ciliary dyskinesia Infection(s), including *necrotizing pneumonia caused by bacteria, viruses, and fungi Bronchial obstruction, due to tumor, foreign body, or mucus impaction bronchiectasis is localized to the obstructed lung segment Chronic inflammatory states: RA, lupus, IBD, COPD, post-lung/bone marrow transplant 25-50% of cases are idiopathic

Answer 107

Obstruction and infection are both necessary but can occur in either order Bronchial obstruction impairs normal clearing mechanisms secretions pool distal to the obstruction and can lead to secondary infection and inflammation Severe infections can lead to inflammation accompanied by necrosis, fibrosis, and eventually airway dilation The smaller airways can become obliterated: bronchiolitis obliterans

Answer 108

Abnormal function or loss of an epithelial chloride channel (CFTR) on chromosome 7

Answer 109

Sweat glands: from the surface into the cell | Other epithelia: from the cell to the lumen

Answer 110

CFTR inhibits ENaC which is found on epithelial cell apical surfaces (except on sweat glands) and thus in CF it is overactive taking up water and Na+ ions from the mucus in the lungs

Answer 111

T he dehydration of the airway mucus leads to decreased ciliary activity and an inability for the body to clear mucous and microbes --> airway obstruction, predispose to (necrotizing) infection --> bronchiectasis primary defect in ion transport --> defective mucociliary action and airway obstruction by thick secretions chronic bacterial infections are common --> widespread damage to airway walls

Answer 112

Staphylococcus aureus, haemophilus influenzae, and burkholderia capacia

Answer 113

Can produce a mucosa capsule (alginate)->protective biofilm

Answer 114

Autosomal recessive Defect in ciliary motor proteins (dynein) --> retention of secretions --> recurrent infection --> bronchiectasis Half of patients also have Kartagener Syndrome: situs inversus or partial lateralizing abnormality, bronchiectasis, and sinusitis Males usually infertile due to sperm dysmotility

Answer 115

Occurs in patients with asthma and cystic fibrosis who develop periods of exacerbation and remission which can lead to proximal bronchiectasis and fibrotic lung disease Hypersensitivity to the fungus aspergillus fumigatus Activation of TH2 helper T cells that recruit eosinophils and other leukocytes Elevated IgE serum antibodies to the fungus Characterized by formation of mucous plugs and intense airway inflammation with eosinophils

Answer 116

Most severe changes in the peripheral lower lobes Affects the more distal bronchi and bronchioles, especially the vertical ones Can affect just a single lung segment if caused by tumors or aspiration of a foreign body Airways may be dilated up to 4x the normal size Appear cystic and filled with mucopurulent secretions In severe cases there can be inflammatory exudation within the walls of the airways that is associated with desquamation of the lining epithelium and lots of ulceration For the rest of the tissue there may be pseudo stratification of the columnar cells or squamous metaplasia Sometimes the necrosis can lead to abscesses If chronic, there can be severe fibrosis and obliteration of the lumens

Answer 117

Staphylococcus (clusters), streptococcus (chains), enterics (gram negatives), anaerobic and microaerophilic pathogens (especially in pediatric populations), Haemophilus influenzae (vaccine), and pseudomonas aeruginosa

Answer 118

signs and symptoms are often episodic and precipitated by URI Persistent, severe cough May be associated with morning or positional changes draining collected pus/secretions into the bronchi Fever, orthopnea, dyspnea, and cyanosis Abundant purulent sputum that is foul smelling and sometimes bloody

Answer 119

Cor pulmonale Brain abscess Amyloidosis

Answer 120

Chronic interstitial and infiltrative diseases - pneumoconiosis - interstitial fibrosis of unknown etiology Chest wall disorders -neuromuscular diseases (poliomyelitis, severe obesity, pleural diseases, kyphoscoliosis

Answer 121

signs and symptoms are often episodic and precipitated by URI Persistent, severe cough May be associated with morning or positional changes draining collected pus/secretions into the bronchi Fever, orthopnea, dyspnea, and cyanosis Abundant purulent sputum that is foul smelling and sometimes bloody

Answer 122

L ong term development of cor pulmonale and 2° pulmonary HTN May be difficult to distinguish in late stages because all result in scarring and gross destruction of the lung End-Stage, or Honeycomb Lung CXR: bilateral lesions that take the form of small nodules, irregular lines, or ground glass shadows that all indicate interstitial fibrosis

Answer 123

Clinicopathologic syndrome of unknown cause with progressive interstitial pulmonary fibrosis and respiratory failure Appears to occur in patients who are genetically susceptible to aberrant repair of recurrent alveolar epithelial cell injuries due to environmental exposures Profibrotic response Histologically, usual interstitial pneumonia (UIP) must be distinguished from other causes UIP == nonspecific pattern of fibrosis shared with connective tissue diseases, chronic hypersensitivity pneumonia, and asbestosis prototypic of restrictive lung disease

Answer 124

Environmental factors: Cigarette smoking, viruses, persistent GERD, metal fumes, wood dust, farming, hairdressers, and stone-polishing Genetic factors: MUC5B: Increased mucin secretion that increases susceptibility to downstream fibrosis this accounts for 1/3 of cases problems in creating surfactant --> unfolded protein response --> harms type II pneumocytes Telomerase: loss-of-function (i.e. autosomal recessive) mutations in TERT and TERC Age > 50 (this is an older person disease

Answer 125

histological pattern of fibrosis is referred to as usual interstitial pneumonia (UIP) this can usually be found on its characteristic appearance in CT scans Lower lobe predominance Patchy interstitial fibrosis (frim rubbery white areas) in sub-pleural and interlobular septal distribution Heterogenous lesions of different ages Earliest lesions contain lots of fibroblastic proliferation (fibroblastic foci) With time areas become more collagenous and less cellular Dense fibrosis and cystic spaces lined with hyperplastic type II pneumocytes or bronchiolar epithelium (end-stage lung, or honeycomb lung) May see signs of pulmonary artery hypertensive changes and diffuse alveolar damage (DAD == ARDS

Answer 126

55-75 years old at presentation with variable deterioration Gradually progressive DOE and dry cough Late: hypoxemia, cyanosis and clubbing despite anti-inflammatories and anti-proliferatives Median survival: 3 years after diagnosis Lung transplant is only definitive therapy

Answer 127

Lung transplant

Answer 128

Diffusely fibrosing disease of unknown etiology | lung biopsies lack the diagnostic features of any of the other well-characterized interstitial diseases

Answer 129

Cellular pattern Mild/moderate chronic interstitial inflammation with lymphocytes and a few plasma cells Uniform or patchy distribution Fibrosing pattern Diffuse or patchy interstitial fibrotic lesions of the same stage (vs other UIP) fibroblastic foci, honeycombing, hyaline membranes and granulomas are absent

Answer 130

patients have chronic dyspnea and cough for several months patients have a much better prognosis vs other interstitial pneumonias Nonsmoking females in 6th decade CT: bilateral, symmetric, predominantly lower lobe reticular opacities Cellular pattern patients tend to be younger than those with fibrosing and have a better prognosis

Answer 131

formerly known as: (bronchiolitis obliterans organizing pneumonia (BOOP) Unknown etiology Cough, dyspnea Patchy subpleural or peribronchial consolidation on CXR *Masson Bodies: polypoid plugs of loose organizing connective tissue within alveolar ducts, alveoli, and often bronchioles Lesions are all of the same age No interstitial fibrosis or honeycombing, the lung architecture is normal patients may recover spontaneously, but most require six months of steroids Identical morphologic changes with infections/inflammatory lung injury organizing pneumonia with intra-alveolar fibrosis is most often seen as a response to infections or inflammatory injury of the lungs

Answer 132

30-40% of patients have pulmonary involvement in one of five ways Chronic pleuritis (+/- effusion) Diffuse interstitial pneumonitis and fibrosis Intrapulmonary rheumatoid nodules Follicular bronchiolitis Pulmonary HTN

Answer 133

Diffuse interstitial fibrosis (nonspecific interstitial pattern more common than usual interstitial pattern) and pleural involvement occurs in this systemic autoimmune disease anti-DNA topoisomerase antibodies

Answer 134

Patchy, transient parenchymal infiltrates or occasionally severe lupus pneumonitis, as well as pleurisy and pleural effusions may occur anti-dsDNA, anti-Smith antibodies

Answer 135

diffuse interstitial fibrosis of the lung --> restrictive lung diseases decreased lung compliance and decreased forced vital capacity, proportionally --> Normal FEV:FVC ratio

Answer 136

Definition Non-neoplastic lung reaction to inhalation of mineral dusts, organic and inorganic particulates, and chemical fumes/vapors encountered in the workplace result from well-defined occupational exposure to specific airborne agents as well as ambient air pollution, especially in urban environments (carbon dust from internal combustion engines) Genetic predisposition is likely because only a small percentage of exposed people develop occupational respiratory disease

Answer 137

depends on: amount of dust retained in the airway and lung (concentration, exposure) cigarette smoking impairs mucociliary clearance and significantly increases the accumulation of dust in the lungs + adds more shit tobacco smoke worsens the effects of all inhaled mineral dusts, especially asbestos Size, shape, particle buoyancy 1-5μm reach terminal alveoli and settle in lining (small particles are worse than large particles) Physiochemical reactivity (toxicity) and particle solubility small and highly soluble: rapid onset lung damage and acute lung injury large and less soluble: more likely to resist dissolution, persist for years, and evoke fibrosing collagenous pneumoconioses (e.g. silicosis) possible additional effects of other irritants (e.g. concomitant tobacco smoking) The particles may also be taken up by the epithelial cells or cross through and interact directly with macrophages and fibroblasts Particles may enter the lymphatics to initiate immune response or cause auto-immune

Answer 138

Spectrum of disease due to inhalation of coal particles and other forms of carbon dust Asymptomatic anthracosis simple coal workers pneumoconiosis: little to no pulmonary dysfunction complicated coal workers' pneumoconiosis aka progressive massive fibrosis (PMF) lung function is compromised Can develop emphysema and chronic bronchitis independent of smoking Presence of silica in the coal dust leads to worse and progressive disease favors progressive disease

Answer 139

Anthracosis macrophage take up inhaled carbon dust and accumulate in interstitial tissue Black pigmented lesions formed by coal laden macrophages accumulate in the connective tissue along the pleural lymphatics or in organized lymphoid tissue along the bronchi or in the lung hilum Simple Coal Workers Pneumoconiosis 1-2mm coal macules with carbon-laden macrophages or slightly larger coal nodules that also contain a delineated network of collagen fibers concentrated in the upper lobes and upper zones of the lower lobes primarily adjacent to respiratory bronchioles (site of initial dust accumulation) With time there can be dilation of adjacent alveoli that gives rise to centrilobular emphysema Complicated Coal Workers Pneumoconiosis (CCWP) also known as Progressive Massive Fibrosis occurs on a background of simple disease; requires years to develop multiple, intensely blackened scars 1 cm or larger consisting of dense collagen and pigment center of the lesion is often necrotic, most likely due to local ischemia

Answer 140

Generally benign, as mild forms have little effect on lung function CCWP may develop causing increased pulmonary dysfunction Pulmonary HTN Cor pulmonale CCWP can continue to worsen, even if exposure is eliminated Does not raise susceptibility of tuberculosis or cancer (in the absence of smoking) domestic indoor use of "smoky coal" (bituminous) for cooking and heating is associated with an increased risk of lung cancer death for both women and men

Answer 141

Definition Common lung disease due to inhalation of pro-inflammatory crystalline silicone dioxide slowly progressing, nodular, fibrosing pneumoconiosis that takes decades Increased risk in African Americans acute silicosis: characterized by the accumulation of abundant lipoproteinaceous material within alveoli etiology == heavy exposure over months to a few years Most prevalent chronic occupational disease in the world

Answer 142

crystalline forms of silica (quartz, cristobalite, and tridymite) are much more fibrogenic than amorphous phagocytosed silica crystals activate the inflammasome --> oxidants, cytokines (IL-1 and IL-18), and GFs --> fibroblast proliferation and collagen deposition Slowly growing collagenous scars -- takes decades to develop Coalesce: progressive massive fibrosis

Answer 143

Nodules are pale or black from coal dust in the beginning Become larger, more diffuse with progression forming large areas of massive fibrosis (scars) that contains a central area of whorled collagen surrounded by dust laden macrophages histologic hallmark lesion characterized by a central area of whorled collagen fibers with a more peripheral zone of dust-laden macrophages Some may have central softening and cavitation from superimposed tuberculosis or ischemia Initial collagenous nodules in upper lung or hilar lymph nodes Thin sheets of calcification can happen around the lymph nodes (called egg shell calcification on CXR) calcium surrounding a zone lacking calcification silicosis == egg shell calcifications Polarized light: (weakly) birefringent silica particles

Answer 144

CXR with fine nodularity in upper lungs pulmonary function tests are either normal or moderately affected early in the course SOB develops later in course with progressive massive fibrosis (most patients do not develop SOB) Continues to worsen even if exposure is eliminated Increased susceptibility to tuberculosis Onset is variable but usually slow and insidious (10-30 years after exposure), but can rarely be rapid with intense exposure 2x increased risk for lung cancer

Answer 145

Family of proinflammatory crystalline hydrated silicates associated with pulmonary fibrosis, carcinoma, mesothelioma and other cancers Think of shipyard workers, construction, demolition (ceiling insulation

Answer 146

Localized fibrous plaques or diffuse pleural fibrosis Pleural effusions (recurrent) Parenchymal interstitial fibrosis (asbestosis) Lung carcinoma Mesothelioma: malignant tumor derived from the lining cells of pleural surfaces Laryngeal, ovarian, extrapulmonary neoplasms Increased risk of autoimmune or cardiovascular disease

Answer 147

Amphiboles Serpentine

Answer 148

More pathogenic form due to their aerodynamic properties and solubility Once trapped, gradually leach due to solubility

Answer 149

Less pathogenic form due to flexible curled shape More likely to become impacted in the upper respiratory passages and subsequently removed by mucocillary elevator

Answer 150

both amphiboles and serpentines are fibrogenic, and increasing doses are associated with a higher incidence of asbestos-related disease (follows a dose-response curve) asbestos can also act as a tumor initiator and promoter -- unlike other inorganic dusts asbestos fibers activate the inflammasome and stimulate the release of proinflammatory factors and fibrogenic mediators Alveolar macrophages ingest the inhaled fibers and produce mediators when activated Fibers act as tumor initiators and promoters Oncogenic effects may be due to free-radical generation Tumorgenicity due to adsorption of potentially toxic substances on the fibers Initial injury occurs at the branch points of small airways and ducts

Answer 151

Morphology Asbestosis: indistinguishable from diffuse interstitial fibrosis (honeycomb pattern) except for the presence of asbestos bodies In contrast to coal workers’ and silicosis, asbestosis begins in the lower lungs and works its way up. The scarring can cause pulmonary HTN and cor pulmonale Asbestos Bodies: pathognomonic, golden brown, fusiform or beaded rods 'dumbbell shaped' with translucent center and consist of asbestos fibers coated with iron-containing proteinaceous material Prussian Blue stain stains iron (saw this in GI with Wilson's disease) Arise via ingestion of asbestos fibers by macrophages Rarely single bodies can be found in healthy people aka Ferruginous Bodies Pleural plaques: well circumscribed plaques of dense collagen, no asbestos bodies, occur with exposure Most common manifestation of asbestos exposure Found on the anterior and posterolateral aspects of the parietal pleura and over the domes of the diaphragm Number and size of the plaques does not correlate with the level or time since exposure Rarely pleural effusions or visceral pleural fibrosis may occur and bind the lung to the thoracic wall localized pleural plaques are asymptomatic

Answer 152

Clinically Dyspnea may occur as the first signs and symptoms 20-30 years after exposure cough associated with production of sputum is likely due to smoking rather than asbestosis CXR: irregular linear densities seen bilaterally in lower lobes (plaques) disease can be static or progress Honeycomb pattern with advanced pneumoconiosis Increased risk of lung cancer if also smoke cigarettes Grim prognosis with concurrent pulmonary/pleural malignancy

Answer 153

Drug Induced Lung Disease Cytotoxic drugs used in cancer therapy (e.g. bleomycin): pulmonary damage and fibrosis as a result of direct toxicity and by stimulating the influx of inflammatory cells into the alveoli Amiodarone: preferentially concentrated in the lung --> pneumonitis ACEI: cough ("very common") IV drug use → pulmonary infection particulate matter in IV drugs --> wedge in the pulmonary microvasculature --> granulomas and fibrosis

Answer 154

well-known complication of therapeutic radiation of thoracic tumors (lung, esophageal, breast, mediastinal) Acute: Occurs 1-6 months post exposure lymphocytic alveolitis, hypersensitivity pneumonitis Fever, Dyspnea not proportional to area radiated Pleural effusion Infiltrates in an area of previous irradiation treatment: steroids

Answer 155

c: occurs if treatment does not take care of the acute pulmonary fibrosis Sequelae of the repair process of the damaged cells Diffuse alveolar damage (DAD) --> ARDS Severe atypia of hyperplastic type II cells and fibroblasts Epithelial cell atypia and foam cells in vessel walls

Answer 156

efinition multi-system granulomatous disease of unknown etiology that can involve several organs and tissues Lung involvement or bilateral hilar lymphadenopathy in 90% of cases Diagnosis of exclusion non-caseating granulomas in various tissues from no identifiable cause only TB leads to caseating granulomas

Answer 157

Most common in patients < 40 US: common in the south 10x more likely in African Americans, rare in Chinese and Southeast Asians More common in females

Answer 158

Accumulation of oligoclonal activated CD4+ T cells (5-15:1 CD4 to CD8) Increased TH1 cytokine production (IL2, IFN-γ) causing T cell expansion and macrophage activation Increased TNF, IL-8, and macrophage inflammatory protein 1α --> granuloma formation Bronchoalveolar TNF level is a marker for disease activity Cutaneous anergy to common skin test antigens (tuberculin, candida) Polyclonal hypergammaglobulinemia

Answer 159

HLA-A1, HLA-BB (class I)

Answer 160

well-formed, non-necrotizing granulomas with tightly clustered epithelioid macrophages and giant cells Granulomas may become enclosed within fibrous rims or may eventually be replaced by hyaline fibrous scars Can coalesce and make small, non-cavitated, noncaseating nodules, located mostly along the lymphatics around bronchi and blood vessels high frequency of granulomas in the bronchial submucosa accounts for the high diagnostic yield of bronchoscopic biopsies Schaumann bodies: Laminated, calcified proteinaceous concretions characteristic of granulomatous disease, not pathognomonic Asteroid bodies: Stellate inclusions within giant cells characteristic of granulomatous disease, not pathognomonic The lesions are likely to heal in the lungs and there are often various stages of fibrosis or hyalinization present

Answer 161

I nvolved in almost all cases, especially the hilar and mediastinal nodes Enlarged, discrete, and sometimes calcified Tonsils can be affected too

Answer 162

S cattered granulomas, especially around the portal triads

Answer 163

Lesions with phalangeal predilection Small circumscribed areas of bone resorption within the marrow creating a diffuse reticulated pattern with widening of the shafts or new bone on the outer surfaces

Answer 164

Discrete subcutaneous nodules or erythematous scaling plaques

Answer 165

Mucus membrane lesions

Answer 166

Iridocyclitis: may lead to corneal opacities, glaucoma, and total loss of vision Decreased lacrimation from inflammation

Answer 167

Bilateral sarcoidosis of the major salivary glands (parotid, submaxilllary, sublingual) Sounds like mucus? So therefore saliva

Answer 168

May be asymptomatic Myopathy: weakness, aches, tenderness, fatigue

Answer 169

Heart, kidney, CNS, endocrine glands (espicially pituitary)

Answer 170

linically May be collateral finding, or patient may present with respiratory abnormalities or constitutional signs and symptoms (i.e. fever, fatigue, weight loss, anorexia, night sweats) Diagnosed via biopsy: non-caseating granulomas rule out other diagnosis based on cultures and stains -- sarcoidosis == diagnosis of exclusion Unpredictable course 65-70% recover with minimal or no residual manifestations 20% have permanent loss of some lung function or some permanent visual impairment 10-15% some die of cardiac or central nervous system damage; most succumb to progressive pulmonary fibrosis and cor pulmonale

Answer 171

Spectrum of immunologically-mediated interstitial disorders due to inhaled organic antigens Primarily affect the alveoli -- extrinsic alveolar alveolitis

Answer 172

F armers lung: actinomycetes spores in hay (thermophilic bacteria) Pigeon breeders lung: proteins from bird feathers or excreta Humidifier/AC lung: bacteria in heated H2O reservoir

Answer 173

Acute phase: proinflammatory chemokines (macrophage nflammatory protein 1a, IL-8) Increased CD4+ and CD8+ T lymphocytes Antibodies to causative agent in serum Complement and immunoglobulins in vessel walls

Answer 174

Interstitial pneumonitis and interstitial fibrosis of the bronchioles Noncaseating granulomas in 2/3 of patients == T-cell mediated (Type IV) hypersensitivity reactions Early cessation of exposure can prevent progression to serious chronic fibrosis and honeycomb lung Intra-alveolar infiltrate

Answer 175

Variable clinical presentation Acutely: recurring fever, dyspnea, cough, leukocytosis 4-6 hours after exposure that may last for days CXR: micronodular interstitial infiltrates Pulmonary Function Tests indicate restrictive lung disease (FEV1:FVC ratio is normal) Progressive exposure: respiratory failure, dyspnea, cyanosis and decrease in total lung capacity and compliance

Answer 176

Increased IL-5 levels attract eosinophils "5Always and 4Ever" except 5 also attracts eosinophils… Relatively rare

Answer 177

Unknown etiology Rapid onset fever, dyspnea and hypoxemic respiratory failure CXR: diffuse infiltrates Broncheolar lavage > 25% eosinophils Diffuse alveolar damage (DAD) == histologic feature of ARDS Prompt response to corticosteroids

Answer 178

``` Induced by Infection (parasitic, fungal, bacterial) Hypersensitivity pneumonitis Drug allergies Association with asthma, allergic bronchopulmonary aspergillosis or Churg-Strauss Syndrome (vasculitis, asthma, MPO-ANCA/p-ANCA ```

Answer 179

Unknown etiology diagnosis of exclusion Focal lung consolidation with extensive lymphocyte and eosinophil infiltration into the walls and the alveolar spaces Cough, fever, night sweats, dyspnea, weight loss Steroid responsive

Answer 180

Large, patchy collections of "Smoker's Macrophages" in alveoli of a current or former smoker

Answer 181

Smoker’s Macrophage: lots of cytoplasm with dusty brown pigment and granular iron; lamellar bodies composed of surfactant inside phagocytic vacuoles Alveolar septa are thickened by a sparse inflammatory infiltrate of lymphocytes, plasma cells, and a few eosinophils Alveolar septa are lined by plump, cuboidal pneumocytes If there is any interstitial fibrosis, it is mild Emphysema is typically present

Answer 182

4-5th decade, no gender preference Insidious onset of dyspnea + dry cough over weeks to months Digit clubbing Pulmonary Function Tests: mild restrictive disease with moderate reduction in diffusing capacity Excellent response to steroids and smoking cessation

Answer 183

Gradual dyspnea and cough of current smokers in their 4th - 5th decade Peribronchiolar inflammation and fibrosis

Answer 184

Patchy bronchiolar accumulations of "Smoker’s Macrophages" in 1st and 2nd order respiratory bronchioles Can also be found in the alveolar ducts Mild peribronchiolar fibrosis is seen that expands the contiguous alveolar septa Centrilobular emphysema is common, but not severe Desquamative interstitial pneumonia is often found in different parts of the same lung

Answer 185

Insidious onset of dyspnea + dry cough over weeks to months | Smoking cessation = improvement

Answer 186

R are disease of young adult smokers Most cases resolve with smoking cessation -- suggests that the lesions are a reactive inflammatory process Focal collections of Langerhans cells (and eosinophils) Langerhans Cells -- immature resident dendritic cells Airway destruction and alveolar damage leads to irregular cystic spaces CXR: cystic and nodular abnormalities Positive for S100, CD1a, CD207 (langerin), and are negative for CD68 Langerhans cells may acquire a BRAF mutation that can lead to a neoplastic process that requires lung transplant

Answer 187

Rare entity characterized by surfactant accumulation in alveoli and bronchioles Defects related to GM-CSF or pulmonary macrophage dysfunction Accumulation of surfactant in intraalveolar and bronchiolar spaces CXR: bilateral patchy, asymmetric pulmonary o

Answer 188

Autoimmune Secondary Hereditary

Answer 189

Autoantibodies against GMCSF cause a functional deficiency, impairing surfactant clearance by macrophages Primarily occurs in adults 90% of all PAP cases No familial predisposition

Answer 190

Uncommon Associated with many diseases that may impair macrophage maturation or function causing inadequate clearance of surfactant from alveolar spaces May follow exposure to irritating dusts/chemicals or in immunocompromised patients

Answer 191

Occurs in neonates and is rapidly fatal Mutations of GMCSF production or signaling Extremely rare

Answer 192

Morphologically Alveoli are filled with granular pink precipitate composed of surfactant proteins Also contain cholesterol clefts Periodic Acid-Schiff (PAS) positive -- PAP is PAS positive Consolidation of large areas of the lungs with minimal inflammation Marked Increased in size and weight of the lungs Surfactant lamellae in type II pneumocytes are

Answer 193

Cough with abundant sputum containing chunks of gelatinous material -- pathognomonic Signs and symptoms may last years with febrile illness High risk for development of 2° infection Progressive dyspnea, cyanosis, and respiratory insufficiency may occur May also be benign with resolution of lesions Treatment: whole lung lavage regardless of underlying defect and GMCSF therapy

Answer 194

Collection of mutations that leads to problems with surfactant

Answer 195

Autosomal recessive, presents in 1st months with rapidly progressive respiratory failure leading to death Sometimes found in older kids and adults that have chronic interstitial lung disease Small lamellar bodies with electron dense cores are diagnostic Most commonly mutated surfactant gene

Answer 196

Autosomal recessive, infant is full term but rapidly develops progressive respiratory distress shortly following birth; death at 3-6 months Lack of surfactant protein B

Answer 197

Autosomal dominant with variable penetrance and clinical course Second most common mutation Lack of surfactant protein C

Answer 198

Variable amount of intra-alveolar granular material, type II pneumocyte hyperplasia, interstitial fibrosis, and alveolar simplification Abnormalities in lamellar bodies in type II pneumocytes

Answer 199

Rare | Develop in presence of pulmonary HTN, pulmonary atherosclerosis, and heart failure

Answer 200

Common in bedridden patients or those with predisposing hypercoagulability occur in 30% of severe burns, trauma, or fracture patients occur in 10% of patient who die acutely in hospitals DVT responsible for 95% of cases

Answer 201

Occur in patient predisposed to clotting Cardiac disease, cancer, prolonged immobilization, hip fracture, hypercoagulability (factor V Leiden), oral contraceptives/pregnancy, obesity, IV lines Response depends on extent of obstruction, size of occluded vessel, number of emboli, CV status and release of vasoactive factors from platelets at thrombosis site Leads to respiratory compromise and/or hemodynamic compromise

Answer 202

Morphology If the emboli are small enough to travel to the peripheral vessels, then it can cause hemorrhage if there is still adequate blood flow to the area or infarct if the patient has compromised cardiovascular function Most of the time the infarcts occur to the lower lobes and there are multiple lesions The infarcts take on a wedge with the apex pointing towards the hilum where the embolus is lodged Look for lines of Zahn on autopsy to know if it post-mortem vs. ante-mortem lines of Zahn present == ante-mortem Septic infarcts: if there are pathogens in the embolus then it will cause there to be neutrophils present

Answer 203

pulmonary infarct is classically hemorrhagic and appears red-blue in early stages with the apposed pleural surface covered by a fibrinous exudate -- overlying fibrinous pleuritis --> pleural friction rub The RBCs begin to lyse within 48 hours and leads to infarct to become paler and red-brown as hemosiderin is produced Eventually there is fibrous replacement that begins at the margins as a gray-white peripheral zone and is eventually converted into a contracted scar

Answer 204

Large Pulmonary Embolus Instantaneous death due to electromechanical dissociation: EKG has rhythm but no blood is entering pulmonary circulation so there is no pulse If the patient lives, then they may appear as though they are having an MI with severe chest pain, dyspnea, and shock

Answer 205

S mall-medium Pulmonary Emboli | Can have similar effects as large emboli but are more likely to be clinically silent

Answer 206

Present as transient chest pain, hemoptysis, cough, fever May eventually have fibrinous pleuritis that can produce a friction rub CXR: there may be a wedge shaped infiltrate 12-36h after the infarct DVTs are diagnosed by duplex ultrasound If enough occur and heal to cause contraction, there can be pulmonary HTN and cor pulmonale

Answer 207

Important prophylactic therapy in patients who have had PE to prevent recurrence anti-coagulation therapy to prevent future clots; fibrinolytic therapy to break apart current clots If not possible patient should receive an IVC filter to prevent clots from reaching the lungs

Answer 208

Mean pulmonary artery pressure>25mmHg at rest

Answer 209

Five WHO Classifications pulmonary arterial hypertension -- diverse collection of disorders that all primarily impact small pulmonary muscular arteries pulmonary hypertension secondary to left-heart failure pulmonary hypertension stemming from lung parenchymal disease or hypoxemia chronic thromboembolic pulmonary hypertension pulmonary hypertension of multifactorial basis

Answer 210

e due to: Chronic obstructive or interstitial disease (group 3) Antecedent congenital or acquired heart disease (group 2) e.g. mitral stenosis Recurrent thromboemboli (group 4) Autoimmune disease (group 1) e.g. systemic sclerosis (scleroderma) Obstructive sleep apnea (group 3) --> pulmonary hypertension and cor pulmonale associated with obesity and hypoxemia Idiopathic or familial up to 80% of idiopathic pulmonary HTN has a genetic basis (autosomal dominant

Answer 211

Bone Morphogenetic Protein Receptor Type 2 (BMPR2): inhibits proliferation, favoring apoptosis first mutation to be discovered in familial pulmonary HTN inactivating mutations are found in 75% of familial cases and 25% of sporadic cases other mutations that converge on the BMPR2 pathway have also been found Mutations lead to vascular smooth muscle hyperplasia and increased vascular resistance Environmental influence or maybe 2-hit is needed to cause diseas

Answer 212

Endothelial dysfunction leads to Increased vascular tone Promotes thrombosis Increased production of cytokines that promote smooth muscle cell proliferation and/or matrix synthesis

Answer 213

Pul monary HTN: Morphology pulmonary artery atherosclerosis Medial hypertrophy of pulmonary muscular and elastic arteries, especially the arterioles and small arteries Right Ventricular Hypertrophy Plexiform lesions: Tufts within capillary channels produce a vascular plexus that spans the lumens of dilated, thin-walled, small arteries that may go outside the vessel Found with 1° pulmonary HTN, HIV (both group 1) and congenital CV anomalies (L2R shunts) (group 2) Numerous organized thrombi (indicate PE

Answer 214

Idiopathic is most common in women 20-40 years old Evident only with advanced disease Progresses to severe respiratory insufficiency and decompensated cor pulmonale (+/- superimposed thromboembolism, pneumonia) Death from decompensated cor pulmonale, often with superimposed thromboembolism and pneumonia, usually ensues within 2-5 years in 80% of patients Treatment: vasodilation and lung transplantation

Answer 215

use Pulmonary Hemorrhage Syndromes Goodpasture syndrome: lung and kidney disease, anti-BM antibodies Wegener's polyangiitis with granulomatosis == lung and kidney disease, but with PR3-ANCA/c-ANCA Idiopathic pulmonary hemosiderosis Vasculitis-associated hemorrhage found in conditions such as hypersensitivity angiitis, Wegener granulomatosis (polyangiitis with granulomatosis), and systemic lupus erythematosus

Answer 216

Autoantibodies against the non-collagenous domain of collagen IV α3 chain (anti-Basement Membrane) Basement membrane destruction in renal glomeruli and pulmonary alveoli Rapidly progressive glomerulonephritis + necrotizing hemorrhagic interstitial pneumonitis Teens to late 20s, especially males Common in active smokers

Answer 217

Smoking, dry cleaning, viral infection | HLA-DRB1*1501 and *1502

Answer 218

Heavy lungs with areas of red-brown consolidation Lungs with focal alveolar wall necrosis Intraalveolar hemorrhage + hemosiderin laden macrophages Later: fibrous thickening of the septae, hypertrophy of type II pneumocytes, and organization of blood in the alveolar spaces Immunofluorescence shows linear Ig depositions along septal basement membranes -- renal throwback

Answer 219

Hemoptysis with focal pulmonary consolidations on CXR (necrotizing interstitial pneumonitis) also hematuria from the rapidly progressive glomerulonephritis (RPGN) Most common cause of death: uremia Treatment: plasmapheresis + immunosuppression therapy should ameliorate lung hemorrhage and glomerulonephritis will emergently perform plasmapheresis in the middle of the night

Answer 220

``` Etiology unknown disease of children Intermittent diffuse alveolar hemorrhage Present with cough + hemoptysis similar to Goodpasture syndrome but there are no anti-basement membrane antibodies detected in serum Treatment: long-term immunosuppression Favorable response Long term patients may develop other immune disorders ```

Answer 221

PR3-ANCA/ c-ANCA (pr-thrEE cEE; C is the 3rd letter of the alphabet) Autoimmune disease Present with hemoptysis most often involves the upper respiratory tract and/or lungs transbronchial lung biopsy might provide the only tissue available for diagnosis Capillaritis -- this is a vasculitis, after all Scattered, poorly formed granulomas (sarcoidosis has well defined granulomas) granulomas with variable necrosis

Answer 222

``` Loss or suppression of the cough reflex Injury to the mucociliary apparatus Accumulation of secretions Interference with phagocytosis or bactericidal actions of alveolar macrophages Pulmonary congestion and edema ```

Answer 223

Incidence increases when defects in innate or humoral immunity are present May also be due to MyD88 germline mutation MyD88 == adaptor for several TLRs that are important for activation of NFκB

Answer 224

Defects in cell mediated immunity can lead to this type of infection Includes mycobacteria, herpes, and pneumocystis jiroveci pneumocystis jiroveci == low virulence

Answer 225

Most common cause of deaths in influenza epidemics == superimposed bacterial pneumonia

Answer 226

Co mmunity Acquired Acute Pneumonia Lung infection in otherwise healthy individuals acquired from the normal environment Bacterial or viral Bacterial Infection Increased CRP and procalcitonin levels -- these are acute phase reactants (IL-6) Often follows a viral URI Causes alveoli to be filled with inflammatory exudate causing consolidation of pulmonary tissue Predisposition: age extremes, chronic disease (CHF, COPD, DM), congenital or acquired immunodeficiency, compromised splenic function (Sickle Cell Anemia or Trait)

Answer 227

Most common cause of community acquired pneumonia; distribution of inflammation is lobar Diagnosis: examine gram stained sputum Gram +ve, lancet-shaped diplococci; encapsulated Endogenous flora in 20% of adults, beware of false-positives isolation of pneumococci from blood cultures is more specific but less sensitive (on 20-30% of patients have positive blood cultures in the early phase of illness) Vaccines for those at high risk contain capsular polysaccharides from common serotypes

Answer 228

Most common bacterial cause of acute exacerbation of COPD Pleomorphic, gram -ve Encapsulated or unencapsulated six serotypes of encapsulated: A through F (Type B is the most virulent) capsular polysaccharide b is incorporated in the widely used vaccine

Answer 229

Pink eye Lower respiratory infection and suppurative meningitis in children (vaccine) Older patients: septicemia, endocarditis, pyelonephritis, cholecystitis, and suppurative arthritis

Answer 230

Unencapsulated Haemophilus influenzae (aka non-typeable) Less virulent Spread along the surface of the upper respiratory tract Can lead to: Otitis media Sinusitis Bronchopneumonia Kids are at more risk if they are premature or have cancer

Answer 231

Can follow a viral URI Pediatric emergency High mortality rate Descending laryngotracheobronchitis can lead to airway obstruction Small bronchi are plugged with dense, fibrin rich exudates with neutrophils Lobular, patchy consolidation (may become confluent and involve the entire lung lobe

Answer 232

Bacterial pneumonia commonly in the elderly second most common bacterial cause of COPD exacerbation Otitis media in children associate with COPD and upper respiratory infection

Answer 233

Streptococcus Pneumoniae: gram +ve, lancet shaped diplococci Haemophilus Influenzae: gram -ve, pleomorphic grown on chocolate agar (along with Legionella) Moraxella Catarrhalis: Staphylococcus aureus pneumonia 2° bacterial pneumonia in children and healthy adults post-viral respiratory illness children: following measles children and adults: following influenza Several complications: Lung abscess, empyema IV drug users are at increased risk in association with endocarditis Often hospital acquired pneumonia (nosocomial) usually secondary to viral respiratory infections

Answer 234

Most frequent cause of gram (-) bacterial pneumonia Affects debilitated patients, chronic alcoholics, and malnourished individuals -- especially chronic alcoholics Three A's: Alcoholics, Aspiration, Abscesses *thick, mucoid (blood tinged) sputum -- "Currant jelly sputum" -- Buzzwords for Boards Organism produces viscid capsular polysaccharide, difficult to expectorate

Answer 235

Pseudomonas aeruginosa pneumonia Common cause of nosocomial infection Invades blood vessels to spread systemically Common in cystic fibrosis, burn patients, and patients with neutropenia

Answer 236

egionella pneumophila pneumonia Causative agent of Legionnaire's disease and Pontiac fever Flourishes in artificial aquatic environments (e.g. HVAC systems) Spreads through aerosolization or aspiration of contaminated water Severe pneumonia in immunocompromised patients, especially patients who have had organ transplant (50% fatal) -- "seen particularly in organ transplant recipients" Diagnose: culture (gold standard), antigens in urine, or antibodies in sputum lobar pattern on CXR, pulse-temperature dissociation lives in amoebas "like mycobacterium tuberculosis, this is a facultative intracellular parasite (lives in macrophages and free living amoebas)" grown on chocolate agar; use a silver stain to detect; urine antigens urine antigens == legionella, streptococcus pneumoniae can enter a low-metabolic state and survive in a biofilm

Answer 237

Sporadic infection or as local epidemics in closed communities such as schools, military camps, or prisons Common in children and young adults "walking pneumonia" "cold agglutinants" "bullous myringitis" -- Bullous myringitis is an infection of the tympanic membrane (the eardrum). Small fluid-filled blisters form on the eardrum and cause severe pain.

Answer 238

Patchy exudative consolidation of the lung parenchyma Focal areas of palpable consolidation that are typically bilateral and basal Well-developed lesions are slightly elevated, dry, granular, grey-red to yellow, and poorly demarcated at the margins Acute neutrophilic suppurative exudation filling bronchi, bronchioles and alveoli that eventually resolves CXR: focal opacities

Answer 239

Consolidation of a large portion of a lobe or an entire lobe CXR: whole lobe is radiopaque streptococcus pneumoniae == most common cause of community-acquired acute pneumonia and the pattern of inflammation is lobar Four Stages of Inflammation Congestion: heavy, boggy, red lung; vascular engorgement, alveolar fluid with few neutrophils and lots of bacteria Red hepatization: massive neutrophilic exudation with RBCs and fibrin that fill the alveolar spaces red, firm, and airless with a liver like consistency Grey hepatization: progressive disintegration of red cells and persistence of fibrinosuppurative exudate that leads to a grey-brown color sequelae of red hepatization Resolution: progressive enzymatic digestion of exudates --> granular, semifluid debris that is resorbed, ingested by macrophages, expectorated, or organized by fibroblast growing into it. May even extend to the surface as pleuritic

Answer 240

``` Abscess formation (especially from Type 3 pneumococci or klebsiella) due to tissue destruction and necrosis Empyema: intrapleural fibrosuppurative reaction infection spreads into pleural cavity causing fibrinosuppurative reaction Bacteremic dissemination to heart valves, pericardium, brain, kidneys, spleen, etc. --> endocarditis, meningitis, suppurative arthritis, etc ```

Answer 241

Abrupt onset of high fever, shaking chills (rigors), productive cough, and occasional hemoptysis Pleural involvement: pleuritic chest pain + friction rub treatment: antibiotics change course of disease within 48-72 hours

Answer 242

Alveoli fluid transudation Upper airways loss of normal mucociliary clearance can predispose to 2° infection interstitial infiltrates

Answer 243

Patchy or lobar areas of congestion without consolidation (atypical) Interstitial pneumonitis occurs with widened, edematous alveolar walls and mononuclear inflammation Hyaline membranes = diffuse alveolar damage Cytopathic changes may occur, including cell death and secondary inflammation

Answer 244

Single stranded RNA virus with 8 strands bound by a nucleoprotein that determines the virus type (A, B or C) Hemagglutinin (H1-3) attach virus to target cells via sialic acid residues on surface polysaccharides antibodies against hemagglutinin prevent infection "glue attaches things" Neuraminidase (N1-2) facilitate release of newly formed virions that are budding from infected cells by cleaving sialic acid residues antibodies against neuraminidase ameliorate infection (Tamiflu) "is the other one" Type A infects humans, pigs, horses, and birds and are the major cause of pandemics and epidemics Type B and C do not mutate, so childhood infection conveys life-long antibody protection

Answer 245

due to mutation in hemagluttinin and neuraminidase proteins (antigenic drift constant because viral RNA polymerase lacks proofreading capability) that create new viral strains which elude antibodies produced to prior exposure to other strains New strains bear some resemblance to prior strains and there is often some resistance to infection in some patients

Answer 246

Hemagluttinin and neuraminidase genes are replaced due to recombination of influenza virus with animal influenza viruses (antigenic shift) All individuals are susceptible to the new virus as it is a completely new viral strain

Answer 247

Hemagluttinin and neuraminidase genes are replaced due to recombination of influenza virus with animal influenza viruses (antigenic shift) All individuals are susceptible to the new virus as it is a completely new viral strain Pathogenesis Enters pneumocytes, inhibits Na+ channels which leads to electrolyte and water in the alveolar lumen Death of infected cells via mRNA translation + apoptosis which exacerbates fluid accumulation Releases "danger signals" activating resident macrophage Induces release of inflammatory mediators Nearby pulmonary endothelium is activated allowing neutrophil extravasation into the interstitium May cause ARDS or lead to 2° bacterial pneumonia Staphylococcus aureus superimposed on top of influenza infection can cause life-threatening 2° pneumonias

Answer 248

high mortality rate -- the virus is deadly transmission is inefficient -- fear is that it will recombine with a highly virulent strain (H1N1, swine flu) Spread through wild and domestic birds -- Avian Flu Is spread throughout the body, not confined to the lung -- systemic Tropism of the hemagluttinin protein is due to ability to be cleaved by diverse proteases, where most are only cleaved in the lung

Answer 249

Paramyxovirus Associated with upper and lower respiratory infections Causes bronchiolitis and pneumonia in the young, old, and immunocompromised clinically indistinguishable from those caused by human respiratory syncytial virus RSV == #1, MPV == #2 -- clinically, they look exactly the same occurs in early childhood and reinfection is common throughout life treatment for immunocompromised patients with ribavirin (anti-viral agent) no current vaccine

Answer 250

Coronavirus that infects the lower respiratory tree and spreads systemically Appeared suddenly in 2002 in China and has not been seen since 2004 Transmitted through respiratory secretions Dry cough, malaise, myalgia, and fever 1/3 recover, remainder progress to severe respiratory disease, 10% die Fatal cases have diffuse alveolar damage + multinucleated giant cells

Answer 251

URI with mucosal hyperemia, swelling, lymphomonocytic and plasmacytic infiltration of submucosa, mucus overproduction which may plug sinuses or Eustachian tubes leading to suppurative 2° bacterial infection Viral tonsillitis is common in kids resulting in hyperplasia within the Waldeyer ring Lung involvement: red-blue areas with congestion Interstitial inflammatory reaction involving walls of the alveoli causing wide alveolar septa If complicated by ARDS, pink hyaline membranes line alveolar walls

Answer 252

Vocal cord swelling and abundant mucus production Bronchocilliary impairment invites 2° infection Focal lung atelectasis due to plugging of small airways (obstruction --> resorption atelectasis) Fibrosis may result if presence of exudates in terminal airways is prolonged and can lead to obliterative bronchiolitis and permanent lung damage superimposed bacterial infection may cause ulcerative bronchitis and bacterial pneumonia

Answer 253

Lung infection can be patchy or extensive involved areas are red-blue and congested interstitial inflammatory reaction involving the alveolar wall tissue with edema + lymphocytes and macrophage Disease extent depends on host immune status, virulence of infecting strain and presence/absence of other complicating factors Variable progression with headache, fever, muscle aches/pains in legs Few localizing signs and symptoms, and may masquerade as URI or chest colds Edema and exudation cause V/Q mismatch causing signs and symptoms out of proportion to scant physical findings Usually mild and resolve spontaneously

Answer 254

Recent hospitalization of 2+ days Presentation from a nursing home/long term facility Attending hospital/hemodialysis clinic Recent IV antibiotic therapy, chemotherapy or wound care More commonly infected with methicillin resistant Staphylococcus Aureus (MRSA) and Pseudomonas Aeruginosa Increased mortality vs. community acquired pneumonia

Answer 255

Pulmonary infection acquired in the course of a hospital stay Increased risk with underlying disease, immunosuppression, prolonged antibiotic therapy, invasive access devices Very increased risk if patient is on mechanical ventilation (Gram -ve bacilli) Most commonly caused by: Gram +ve cocci: Staphylococcus Aureus and Streptococcus Pneumonia Gram -ve rods: Enterobacteriaceae and Pseudomonas Gram -ve bacilli: ventilator associated pneumonia

Answer 256

``` Occurs in markedly debilitated patients with abnormal gag and swallowing reflexes Pneumonia is chemical + bacterial Aerobes > anaerobes Fulminant necrotizing pneumonia Frequent cause of death Complication in survivors: lung abscess Klebsiella ```

Answer 257

Occurs in almost all people, especially in patients with GERD Results in inconsequential poorly formed non-necrotizing granulomas Multinucleated foreign body cell reaction May exacerbate preexisting lung diseases like asthma, interstitial fibrosis, and lung rejection

Answer 258

Local suppurative necrosis of lung tissue Air fluid levels are very characteristic

Answer 259

Streptococci, Staphylococcus Aureus, many gram -ve organisms Commonly mixed infection due to aspiration which means many anaerobic oral cavity organisms (Bacteroides, Fusobacterium, Peptococcus *60%)

Answer 260

Antecedent primary lung infection from things like Staphylococcus aureus, Klebsiella pneumoniae, and type 3 pneumococcus Septic embolism Neoplasia obstructing the bronchopulmonary segment Bacteria spreading from somewhere else in the bod

Answer 261

Aspiration based ones are more common on the right and single Pneumonia based abscesses are typically located basally and are found in multiple diffusely scattered Septic based abscesses are multiple and can involve any region of the lung

Answer 262

Single or multiple Microscopic to large cavities Histology: suppurative destruction of the lung parenchyma within the central area of cavitation Pus or air depending on available drainage Chronically may be surrounded by a reactive fibrous wall surrounding large, poorly demarcated, fetid, green-black gangrene

Answer 263

Presents as cough, fever, chest pain, weight loss, and copious amounts of foul smelling purulent or sanguineous sputum bronchiectasis and lung abscess == foul smelling sputum Clubbing of the fingers can develop in a few weeks Can be complicated by extension into pleural cavity, hemorrhage, septic embolization, 2° amyloidosis Confirm with CXR treatment: antimicrobials resolve most cases with a scar

Answer 264

When there is no discernible basis for the abscess formation

Answer 265

Localized inflammation in immunocompetent patients without regional lymph node involvement Asymptomatic Limited granulomatous disease In immunocompromised patients the infection can become disseminated Fulminant, widespread disease

Answer 266

Intracellular pathogen of phagocytes, endemic to Ohio and Mississippi river valleys (midwest) Acquired via inhalation of dust with bird/bat excreta (caves) bird can also --> hypersensitive pneumonitis Mainly only infects immunocompromised patients macrophages are the major target of infection

Answer 267

Self-limited, latent, 1° pulmonary involvement which may result in coin lesions on CXR Chronic, progressive, 2° lung disease localized to the lung apices causing cough, fever, and night sweats Spread to extrapulmonary sites (e.g. mediastinum, adrenals, liver, meninges) widely disseminated disease in immunocompromised patients

Answer 268

Produces granulomas with caseating, coagulative necrosis which undergo fibrosis and concentric calcification (tree-bark appearance) -- can eventually lead to bronchiectasis? Silver stain identifies 3-5 micron cysts of the fungus that can persist for years (and differentiates this fungus from tuberculosis) Fulminant disseminated histoplasmosis: Immunocompromised patients. Focal accumulations of mononuclear phagocytes filled with fungal yeasts throughout the body, NO granulomas for fungal infections, stain with silver or PAS 3-5 micrometer pear shaped intracellular yeast

Answer 269

Look for the antigens in the tissues in the beginning and then antibodies after 2-6 weeks coin lesion differential: histoplasma, hamartoma, adenocarcinoma

Answer 270

Soil dwelling, dimorphic fungus that occurs in central and southeast USA (Florida) also Canada, Mexico, Middle East, Africa, and India

Answer 271

Pulmonary, disseminated or primary cutaneous (rare)

Answer 272

Usually upper lobe involvement with abrupt productive cough, head ache, chest pain, weight loss, fever, abdominal pain, night sweats, chills, and anorexia CXR: lobar consolidation, multi-lobar infiltrates, perihilar infiltrates, multiple nodules, miliary infiltrates Upper lobes are most commonly involved Typically resolves spontaneously

Answer 273

(BBBB) Blastomycosis: broad based budding Immunocompetent host: suppurative granulomas with persistence of yeast cells due to limited macrophage capabilities to kill this fungus 5- 15 micron yeast cells that divide by broad based budding Thick double-contoured cell wall with visible nuclei Involvement of the skin and larynx is associated with marked epithelial hyperplasia, can be mistaken for squamous cell carcinoma 5-15 micrometers yeast with broad based budding

Answer 274

``` outhwest USA, Mexico deserts (Arizona) everyone who inhales the spores of Coccidioides immitis becomes infected and develops a delayed-type hypersensitivity reaction to the fungus Inhaled spores (arthroconidia) block fusion of the phagosome and lysosome in the macrophage and resist intracellular killing ``` Inhaled spores (arthroconidia) block fusion of the phagosome and lysosome in the macrophage and resist intracellular killing

Answer 275

Most cases are asymptomatic San Joaquin Valley Fever complex: 10% of infected people develop lung lesions, fever, cough, pleuritic pains, erythema nodosum, and erythema multiforme less than 1% of people develop disseminated Coccidioides immitis infection which involves the skin and meninges (Filipinos and African-Americans are at increased risk of disseminated disease

Answer 276

Within macrophages, the fungus is seen as thick-walled, nonbudding spherules 20-60 microns and filled with endospores Spherule rupture, releasing endospores causes a superimposed pyogenic reaction and may recruit neutrophils Lesions can be granulomatous or pyogenic or mixed, with the disseminated type favoring more of the pyogenic type 20-60 micrometer nonbudding spherules

Answer 277

Opportunistic infections rarely affect normal hosts, but in this setting can cause life-threatening pneumonia appearance of a pulmonary infiltrate, with or without signs of infection (e.g. fever), is serious in patients whose immune system is suppressed by disease, immunosuppressive therapy for transplant, chemotherapy, or irradiation Often multiple organisms are involved Bacteria: Pseudomonas, Legionella, Listeria, mycobacteria Viruses: CMV, herpes Fungi: Pneumocystis jiroveci (AIDS defining), Candida, Aspergillus, phycomycetes, Cryptococcus neoformans

Answer 278

Serious issues can be caused by the "normal" lower respiratory infection pathogens (Streptococcus pneumonia, Staphylococcus aureus, Haemophilus influenza, gram -ve rods) the usual pathogens are among the more serious bacterial pneumonias in HIV patients are more common, more severe, and more often associated with bacteremia than in those without HIV infection Pulmonary disease may be due to multiple causes and signs and symptoms can be atypical Base on the Stage of Disease (HIV/AIDS) CD4+ > 200 = bacterial and tubercular infection CD4+ 50-200 = Pneumocystis -- AIDS defining illness CD4+ < 50 = CMV, fungal and Mycobacterium avium

Answer 279

Emphysema (pink puffer) [chronic bronchitis == blue bloater] -- not candidate for lung transplant Idiopathic pulmonary fibrosis == end stage lung, honeycomb lung Cystic Fibrosis 1° pulmonary HTN

Answer 280

Usually single

Answer 281

Early are bacterial ganciclovir prophylaxis and matching of donor-recipient CMV status == reduced frequency and severity of CMV pneumonia (because everyone has CMV but nobody is sick with CMV) Most common 3-12 months post-operative Acute rejection: all patients to varying degrees despite immunosuppression If fungal: due to aspergillus and candida

Answer 282

inflammatory infiltrates around small vessels or in the submucosa of airways Several weeks to months after surgery, but may also present years later Fever, dyspnea, cough, radiologic infiltrates Looks like infection, so need biopsy to rule out pathogens Inflammatory infiltrates

Answer 283

Happens to at least 50% of patients after 3-5 years Cough, dyspnea, and irreversible decrease in lung function due to pulmonary fibrosis Bronchiolitis obliterans partial or complete occlusion of small airways by fibrosis +/- inflammation; patchy; difficult to treat

Answer 284

90-95% carcinoma 5% bronchial carcinoid 2-5% mesenchymal and other miscellaneous

Answer 285

Most frequently diagnosed major cancer in the world Most common cause of cancer mortality worldwide Mostly due to tobacco smoke Commonly occurs between 40-70 years old

Answer 286

Small cell -- TB, TP53, and MYC Non-small cell Squamous cell -- RB, TP53, p40, hypercalcemia, keratin pearls and intercellular bridges Adenocarcinomas -- EGFR, ALK, ROS, MET, RET, KRAS

Answer 287

Females have Increased susceptibility to the associated carcinogens Risk of lung cancer is proportional to the amount and duration of smoking Cessation decreases risk after 10 years, but not to baseline Individuals with P450 polymorphisms have a greater risk of lung cancer due to activation of pro-carcinogens Increased chromosome breakage sensitivity in peripheral blood lymphocytes = 10x risk

Answer 288

Asbestos (10-30 year latency, 5x risk, if smoker 55x) Arsenic Chromium Uranium (exposed miners 4x risk, if smoker then 10x risk) Nickel Vinyl chloride -- hepatic adenocarcinoma Mustard gas Ionizing radiation (Hiroshima, Nagasaki, Chernobyl

Answer 289

Add to risk of lung cancer in those who smoke via inflammation and repair

Answer 290

Loss of tumor suppressor genes due to tobacco smoke exposure Loss of CDKN2A (3p, 9p) = loss of p16 (RB) Loss of TP53 (17p) *highest frequency of TP53 mutations of all histologic types of lung carcinoma highly associated with exposure to tobacco smoke and harbors diverse genetic aberrations, many of which are chromosomal deletions involving tumor suppressor loci (two hits needed) Loss of RB Amplification of FGFR1 More common in the central/hilar region of the lung squamous cell carcinoma is more common (20%) than small cell carcinoma (14%) keratin pearls and intercellular bridges

Answer 291

``` Strongest association with smoking TP53 loss of function (75-90%) RB mutations are most likely (~100%) in small cell carcinomas Chromosome 3p deletion MYC amplification Aggressive, high mortality ```

Answer 292

Gain-of-function of GF receptor signaling pathways Tyrosine kinases: EGFR, ALK, ROS, MET, RET, KRAS KRAS mutations are the worst More common in the peripheral lung Precursor lesions Atypical adenomatous hyperplasia (≤ 5mm) Adenocarcinoma in situ < 3 cm; mucinous, atypical cells

Answer 293

More common in women Most are adenocarcinomas More likely to have EGFR mutation, and almost never have KRAS mutations TP53 is less common than in those who smoke

Answer 294

Squamous dysplasia and CIS Atypical adenomatous hyperplasia Adenocarcinoma in situ Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia

Answer 295

Via the predominant histologic appearance, though multiple histologies can be present in one tumor clinical significance is still undetermined four major histologic subtypes Adenocarcinoma (38%) Squamous cell carcinoma (20%) Small cell carcinoma (14%) treat with chemotherapy because almost all are metastatic at presentation Large cell carcinoma (3%) Other (25%)

Answer 296

Single or multiple, small lesion characterized by dysplastic pneumocytes lining alveolar walls that are mildly fibrotic In the lung adjacent to invasive tissue or away from it

Answer 297

Single (favorable) or multiple in the terminal bronchioloalveolar regions Composed entirely of dysplastic cells growing along preexisting alveolar septae lepidic? Excessive dysplasia (more than atypical adenomatous hyperplasia) Tall, columnar +/- intracellular mucin (mucinous vs. nonmucinous) No gender specificity, no association with smoking Dismal prognosis if diffuse tumors 3 cm or less in diameter characterized by pure growth along pre-existing structures (lepidic pattern) without stromal invasion lepidic == rind, skin, or membrane epithelium are normal, lining cells are abnormal

Answer 298

Most common lung cancer in the absence of smoking Common in the peripheral lung Malignant epithelial tumor with glandular differentiation or mucin production Grow in various patterns majority express thyroid transcription factor 1 (TTF-1) Lepidic pattern of spread as tumor cells crawl along pre-existing alveolar septa without stromal invasion Associated with TTF1 and napsin A Grow more slowly, but metastasize earlier vs. squamous cell carcinoma

Answer 299

Tumors ≤ 3cm with a small invasive component (≤ 5mm) Associated with scarring and peripheral lepidic growth pattern Better outcome vs. invasive carcinoma of comparable size

Answer 300

S olitary or multiple nodules Potentially consolidate an entire lobe with tumor cells resembling lobar pneumonia less likely to be cured with surgery Spread aerogenously forming satellite tumors

Answer 301

Commonly in men, strongly associated with smoking most common lung cancer associated with smoking because this is more likely than squamous cell cancer (20% vs 14%... not how stats work but OK) Antedated squamous metaplasia/dysplasia in the bronchial epithelium that transforms to CIS CIS is cytologically identifiable by sputum or lavage, but undetected on CXR and is asymptomatic Can grow to obstruct the bronchus causing distal atelectasis and infection May penetrate the wall of the bronchus and infiltrate peribronchial tissue

Answer 302

'Cauliflower' mass Grey/white, firm neoplastic tissue If there is hemorrhage or necrosis, they appear as red-yellow mottling and can cavitate Keratinization (squamous pearls) or intercellular bridges There is more that is seen in well differentiated tumors and is only focally present in undifferentiated tumors Increased mitotic activity in poorly differentiated tumors Closest correlation with smoking Commonly in the central/hilar region Associated with p53 and p40 markers Late metastases Surrounding tissue is typically dysplastic Paraneoplastic Syndromes == hypercalcemia

Answer 303

Hypercalcemia

Answer 304

Highly malignant, metastasizing widely (high grade), almost always fatal Strongest lung cancer association with smoking Arises in the major bronchi or in the periphery of the lung -- central There is no known pre-invasive phase Small cells with scant cytoplasm, ill-defined borders, finely granular nuclear chromatin (salt & pepper) + lack of nucleoli Nuclear molding is prominent High mitotic count Don’t show glandular or squamous organization Necrosis is common and often extensive Azzopardi effect: Basophilic staining of vascular walls due to encrustation by DNA from necrotic tumor cells Cells may originate from neuroendocrine progenitor cells with dense-core neurosecretory granules Expression of chromogranin, synaptophysin, CD57, hormonal secretion (paraneoplastic) Lung cancer most commonly associated with ectopic hormone production BLC2 found on immunohistochemistry Paraneoplastic Syndromes == SIADH and Cushing (ectopic cortisol)

Answer 305

Small cell carcinoma is mixed with non small cell histologies May resemble sarcoma

Answer 306

Undifferentiated malignant epithelial tumor lacking cytologic features of other lung cancers Diagnosis of exclusion Variant may express neuroendocrine components, but tumor cell size is much larger than small cell carcinoma Prominent nucleoli

Answer 307

May extend onto the pleural surface, spread within the pleural cavity or into the pericardium Most cases (> 50%) metastasize to the bronchial, tracheal and mediastinal lymph nodes Lymphatic and hematogenous spread occurs Metastasize early except squamous cell carcinoma Metastasis may be the first manifestation 50% of metastatic cases involve the adrenals Other common sites include liver, brain and bone

Answer 308

Combined carcinoma Where there are more than 1 type of tumor cell present in the mass happens in approximately 10% of all lung carcinomas

Answer 309

partial obstruction --> focal emphysema total obstruction --> Atelectasis (resorption kind) impaired drainage --> Suppurative or ulcerative bronchitis or bronchiectasis Pulmonary abscesses Superior vena cava syndrome Pericarditis Pleuritis Invasion of neural structures near trachea → Horner syndrome *Pancoast tumors Partial Ptosis Anhidrosis Miosis (increase in sympathetics, constricted pupil

Answer 310

Cough, weight loss, chest pain, dyspnea Poor prognosis, especially with metastasis (common to adrenals, brain, liver and bone) adenocarcinoma and squamous cell carcinoma tend to remain localized longer and have a slightly better prognosis than do the undifferentiated cancers, which are usually advanced by the time they are discovered small cell cancer (oat cell cancer) is virtually always fatal 5 year survival 52% if disease is localized at presentation 22% with regional metastases 4% with distant metastases Survival is prolonged if targeting adenocarcinoma that have the EGFR mutation -- just like breast cancer Survival is reduced if there is a KRAS mutation (worse prognosis) Small cell carcinoma: sensitive to radiation and chemotherapy if localized, but most patients present with metastases Pathoma: "so small the surgeon can't see it"

Answer 311

Small Cell Carcinoma SIADH: hyponatremia due to inappropriate/excess ADH secretion Cushing Syndrome: ACTH

Answer 312

Hypercalcemia: parathormone, parathyroid hormone-related peptide, PGE2, cytokines Hypocalcemia: calcitonin Gynecomastia: gonadotropins Carcinoid syndrome: 5HT, bradykinin, MEN1

Answer 313

Muscle weakness due to auto-antibodies directed against the neuronal Ca++ channel better with activity myasthenia gravis == fatigable ptosis (better with rest) Hypertrophic pulmonary osteoarthropathy (associated with clubbing of the fingers) Acanthosis nigricans Peripheral neuropathy (sensory) Leukemoid reaction Hypercoagulable states (Trousseau

Answer 314

Apical Lung Cancer arising from the superior pulmonary sulcus tend to invade neural structures near trachea (cervical sympathetic plexus) Horner Syndrome: ptosis, miosis, anhidrosis -- "PAM is horny" Ipsilateral severe pain in ulnar nerve distribution

Answer 315

Precursor to the development of tumorlets and typical or atypical carcinoids tumorlet == small, inconsequential (benign), hyperplastic nest of neuroendocrine cells seen in areas of scarring or chronic inflammation carcinoids may occur in patients with multiple endocrine neoplasia (MEN) type 1 Rare disorder

Answer 316

Typical or atypical, low-grade malignant epithelial neoplasms Epidemiology < 40 years, no gender specificity 20-40% are nonsmokers

Answer 317

May arise centrally or peripherally Central may protrude into bronchial lumen and are covered by an intact mucosa Peripheral are solid and nodular Organoid, trabecular, palisading, ribbon, or rosette-like arrangements of cells separated by a delicate fibrovascular stroma Cells are regular and have a uniform round nuclei and a moderate amount of eosinophilic cytoplasm Most are confined to mainstem bronchi May penetrate bronchial wall, fanning out 'collar button lesion'

Answer 318

Coughing, hemoptysis, impaired drainage, bronchiectasis, emphysema, and atelectasis can all happen secondarily to the growing lesion Carcinoid syndrome: intermittent attacks of diarrhea, flushing, and cyanosis occurring in 10% of patients due to tumor secretion of vasoactive amines (5HT) 5 year, 95% survival for typical 5 year, 70% survival for atypical

Answer 319

Fewer than 2 mitosis/10 high powered fields

Answer 320

``` Increased pleomorphism Prominent nuclei Increased mitotic activity Increased risk of lymphatic invasion 2-10 mitoses/10 high-powered fields and/or foci of necrosis ```

Answer 321

Radio-opacity 'coin lesion’ on routine CXR coin lesions on CXR == histoplasma, lung hamartoma, adenocarcinoma Well circumscribed, solitary -- low-grade, benign? Nodules of connective tissue (cartilage, fibrous, fat) intersected by epithelial clefts Can be cancerous if associated with chromosome problems with 6 or 12

Answer 322

Young women of childbearing age present with dyspnea or spontaneous pneumothorax Proliferation of perivascular epithelioid cells with markers of melanocytes and smooth muscle cells Cystic, emphysema like expansion of terminal airspaces, thickening interstitium and obstruction of lymphatic vessels lesional epithelioid cells appear to frequently harbor loss of function mutations in the tumor suppressor TSC2, one of the loci linked to tuberous sclerosis tuberin == negative regulator of mTOR (mutation leads to increased mTOR activity) mTOR plays a function in regulating metabolism Slow progression over several decades Definitive treatment: lung transplantation

Answer 323

Children, no gender preference Fever, cough, chest pain, hemoptysis Grey/white, round, well defined single peripheral mass, with calcium deposits Proliferation of fibroblasts, myofibroblasts, lymphocytes, plasma cells Peripheral fibrosis Some have ALK mutation Treatment with ALK inhibitors have produced response

Answer 324

multiple discrete nodules (cannonball lesions) are scattered throughout all lobes, more being at the periphery

Answer 325

Normally 15 ml of serous, acellular, clear fluid lubricates the pleural surface May occur due to Increased hydrostatic pressure (CHF) Increased vascular permeability (pneumonia) Increased negative intrapleural pressure (atelectasis) Decreased oncotic pressure (nephrotic syndrome) Decreased lymphatic drainage (carcinomatosis

Answer 326

Associated with underlying pulmonary inflammation tuberculosis, pneumonia, infarct, abscess, systemic disease Fluid exudate is resorbed with resolution or organization of fibrinous components Respiratory distress may occur due to fluid accumulation compressing the lung

Answer 327

Reflects pleural space infection causing accumulation of pus (yellow, creamy

Answer 328

Likely due to bacterial or mycotic seeding via spread from intrapulmonary infection Less frequently due to lymphatic or hematogenous spread from a distant source Rarely due to infection below the diaphragm (liver abscess), more common on the right side

Answer 329

Loculated, yellow-green, creamy pus with neutrophils and other leukocytes chylothorax == milky white Small, localized volume Commonly, organizes into dense, tough fibrous adhesions that obliterate the pleural space or envelop the lungs, significantly restricting pulmonary expansion

Answer 330

Sanguineous inflammatory exudates due to bleeding disorders, neoplasm, or rickettsial disease Look for exfoliated tumor cells Must differentiate from hemothorax

Answer 331

Noninflammatory pleural effusion within the pleural cavity Clear, straw-colored fluid unilateral or bilateral most common cause is cardiac failure, and thus it is often accompanied by pulmonary congestion and edema Usually due to heart failure, but also in renal failure and liver cirrhosis

Answer 332

Noninflammatory pleural effusion Blood in the pleural cavity Fatal complication of ruptured aortic aneurysm or vascular trauma May occur post-operatively

Answer 333

Noninflammatory pleural effusion Accumulation of milky fluid (often of lymphatic origin) pus is creamy and yellow Milky white due to emulsified fats due to thoracic duct trauma or obstruction causing secondary rupture of major lymphatic ducts, usually malignancies

Answer 334

Young patients Rupture of small, peripheral, usually apical sub-pleural blebs Subsides as air is resorbed Recurrent attacks may occur and are disabling

Answer 335

Defect between airways and pleura act as a one way valve Air enters during inspiration but is not released during expiration Progressively increasing pleural pressure compresses the contralateral lung and mediastinal structures (possibly fatal) trachea deviates away from the side of the tension pneumothorax

Answer 336

Usually metastatic tumors from the lung and breast Leads to serous or serous-sanguineous effusion that contains neoplastic cells careful cytologic examination of the sediment is of considerable diagnostic value

Answer 337

Noninvasive, solitary fibrous tumor Attached to pleural surface via a pedicle -- pedunculated? Small or large

Answer 338

Solitary fibrous tumor with dense fibrous tissue with occasional cysts filled with viscous fluid Whorls of reticulin and collagen fibers with interspersed spindle cells resembling fibroblasts CD34 +ve and Keratin -ve malignant mesotheliomas show the opposite phenotype Inversion of chromosome 12 (NAB2 -STAT6 rearrangement) NAB2-STAT6 --> fusion gene virtually unique to solitary fibrous tumor hypothesized to be a key driver of tumor development No relation to asbestos exposure Resection is curative

Answer 339

Uncommon tumor of mesothelioma cells int he visceral or parietal pleura

Answer 340

90% of cases are related to asbestos exposure 25-45 year latency Smoking has no impact (< risk than lung carcinoma) Asbestos bodies and plaques may be seen

Answer 341

Chromosome 9: CDKN2A/INK4A deletion (tumor suppressor) | Chromosome p16 deletion

Answer 342

``` Tumor is spread diffusely over the lung surface and fissures to form an encasing soft, gelatinous, gray-pink tumor sheathe Three Patterns Epithelioid (60%) Sarcomatoid (20%) Biphasic/mixed (20%) ```

Answer 343

Epithelium like cells form tubules and papillary projections resembling adenocarcinomas with cuboidal, columnar, or flattened cells +ve for cytokeratin proteins, calretinin, WT1 (Wilms Tumor), cytokeratin 5/6 and D2-40 opposite of a solitary fibrous mass

Answer 344

Sarcomatoid Pattern Malignant, spindle-shaped cells resembling a fibrosarcoma Lower expression of markers seen in other morphologic patterns Usually cytokeratin +ve

Answer 345

Contains both epitheliooid and sarcomatoid patterns

Answer 346

Chest pain, dyspnea, recurrent pleural effusions 20% with pulmonary asbestosis (fibrosis) Metastasize to the hilar lymph nodes, lung, liver and other organs 50% 1 year mortality, few survive > 2 years Can arise in other areas (peritoneum, pericardium, etc.) And if affects the GI tract, can lead to death due to intestinal obstruction or inanition