Robbin 15 and 16 Flashcards
_ is a defective development of both lungs resulting in decreased wt, vol, and acini for body wt and gestational age. It is caused by _
pulmonary hypoplasia, caused by anything that compress the lungs or impede normal lung expansion in utero such as congenital diaphragmatic hernia and oligohydramnios.
Foregut cysts are abnormal detachments of primitive foregut and most often located in _
hilum and middle mediastinum
The walls of bronchogenic cyst contains _
bronchial glands, cartilage and smooth muscle, usually present due to compression of nearly structures or found incidentally.
what is pulmonary sequestration?
discrete area of lung tissue that 1) lacks any connection to airway system and 2) has an abnormal blood supply arising from the aorta or its branches.
extralobar and intralobar sequestration differ by their presentation how?
Extralobar external to the lung and come to attention in infants as a mass lesion. Intralobar occur within lung and present in older kids often due to recurrent localized infection or bronchiectasis.
Atelectasis differs in infants vs adults how?
Infants = incomplete expansion Adults = collapse of previously inflated lung creating areas of airless parenchyma
Adult or acquired atelectasis produces a well _ regions but poorly _, predisposing for infection.
well perfused. poorly ventilated
Adult or acquired atelectasis comes in what three flavors?
- Resorption atelectasis
- Compression atelectasis
- Contraction atelectasis.
_ atelectasis is a consequence of complete obstruction without impairment of blood flow
Resorption
In resorption atelectasis, decreased lung volume results in a mediastinal shift to which side?
affected side
What are some causes of resorption atelectasis?
mucous plug associated with asthma, bronchitis, aspiration pneumonia, foreign body etc.
_ is consequence of partially or totally filled pleura with exudate (CHF), tumor, air (pneumothorax), blood (hemothorax), when air pressure threatens the function of lungs and great vessels (tension peumothorax), or with an extra-pulmonary mass compressing lung parenchyma
Compression atelectasis
In compression atelectasis, compression pushes lung and results in a mediastinal shift to which side?
away from the affected side
what is contraction atelectasis?
Fibrotic changes prevent expansion, resulting in reduced lung volume and ventilation. This is the only irreversible atelectasis.
_ is the accumulation of fluid in alveolar space due to either 1) increased capillary hydrostatic pressure, 2) decreased capillary oncotic pressure or 3) an increased vascular permeability
Pulmonary edema
1 is due to increased hydrostatic pressure and most commonly associated with 2 sided congest heart failure.
- Hemodynamic pulmonary edema.
2. Left
In _ pulmonary edema basal regions develop edema first (dependent edema) b/c pressure is great in dependent areas, and alveolar macrophages have hemosiderin in them called siderophages or heart failure cells. As this progresses fibrosis and thickening of the affected areas results in a gross brown and firm appearance called brown induration
hemodynamic
_ is a type of edema that is dependent on an increased capillary permeability
microvascular injury pulmonary edema.
Microvascular injury pulmonary edema is most commonly associated with _
pneumonia. but can also be caused by inhaled gases (O2, smoke) liquid aspiration (near-drowning) or trauma
In microvascular injury pulmonary edema, edema begins in 1 and then moves into 2
- vascular ednothelium
2. alveoli
_ can result from the extreme case of microvascular injury pulmonary edema
acute respiratory distress syndrome
What are some morphological findings of acute respiratory distress syndrome?
acute gross = heavy, firm, red, and boggy lungs
Acute histo: interstitial and interalveolar edema, inflammation (neutrophils), hyaline membrane = fibrin rich edema with cytoplasmic/lipid remnants
_ is a manifestation of severe acute lung injury characterized by abrupt onset of significant hypoxemia and bilateral pulmonary infiltrates in the absence of cardiac failure
Acute respiratory distress syndrome
In the pathogenesis of ARDS, list the chain of events from initiation to resolution
- Endothelial activation: injury sensed by resident alveolar macrophages which secretes mediators such as TNF. these mediators can directly injury endothelial cells or activate endothelial cells to express increased levels of adhesion molecules procoagulant proteins and chemokines
- Adhesion and extravasation of neutrophils: neutrophils adhere to activated endothelium and migrate into interstitium and alveoli and release inflammatory mediators including ROS, and cytokines. Macrophages migration inhibitory factor (MIF) also helps to sustain ongoing inflammation –> increased recruitment and adhesion of leukocytes, causing more endothelial injury, local thrombosis
- Accumulation of intraalveolar fluid and formation of hyaline membranes. damage to type II alveolar cells –> surfactant abnormalities –> compromise gas exchange. Ultimately the debris of dead cells forms hyaline membranes
- Resolution of injury is impeded in ALI/ARDs due to epithelial necrosis and inflammatory damage that impairs ability of remaining cells to assist with edema resorption. If inflammatory stimulus is lessened, macrophage remove intraalveolar debris and release fibrogenic cytokines such as TGFb and PDGF which stimulate fibroblast and collagen deposition leading to fibrosis of alveolar walls. Bronchiolar stem cells proliferate to replace pneumocytes.
what are some causes of ARDS?
- infection (pneumonia, sepsis (typically gram negative sepsis)
- aspiration
- acute pancreatitis
- trauma with shock
- amniotic fluid embolism
- uremia
How to patients with ARDS present clinically?
- Profound dyspnea and tachypnea
- cyanosis and hypoxemia, respiratory failure and appearance of diffuse bilateral infiltrates on Xray.
How is ARDS treated?
- respiratory support and treat underlying cause
- mechanical ventilation with low tidal volume
- PEEP (positive end-expiratory pressure) to prevent airway collapse at end expiration, recruits collapsed alveoli. together increases FRC and decrease shunting
_ is widespread acute lung injury associated with rapidly progressive clinical course. Usually occurs age 59. Patients presents with acute respiratory failure often following an illness of less than 3 wks duration that resembles an URI
Acute interstitial pneumonia
_ lung disease are characterized by an increase in resistance to airflow due to partial or complete obstruction at any level from the trachea and larger bronchi to the terminal and respiratory bronchioles.
Obstructive
FEV1/FVC ratio less _ generally indicates airway obstruction
0.7
_ is characterized by reduced expansion of lung parenchyma and decreased total lung capacity
restrictive disease
In restrictive lung disease FEV1/FVC ratio is _
normal
Restrictive lung disease occur in what two broad conditions?
- chest wall disorders ( severe obesity, pleural disease, kyphoscoliosis, and neuromuscular disease such as poliomyelitis
- chronic interstitial and infiltrative disease such as pneumoconioses and interstitial fibrosis.
Emphysema, chronic bronchitis, asthma and bronchiectasis are all what kind of lung disease?
Obstructive Lung disease
What two lung diseases are often grouped as COPD?
emphysema and chronic bronchitis, because most patients have features of both since major trigger is smoking
_ is characterized by irreversible enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls without obvious fibrosis leading to increased work to breathe
Emphysema
Emphysema is classified into what four types?
- centriacinar (most common, 95%)
- panacinar
- paraseptal
- irregular
1 and 2 causes clinically significant airflow obstruction
In centriacinar emphysema, which part of the respiratory bronchioles are affected?
central or proximal parts of the acini. distal alveoli are spared. Lesion are more severe in upper lobes, particularly in the apical segments. Normal and emphymatous airspaces coexist within the same acinus and lobule
In this form of emphysema, the acini are uniformly enlarged from the level of respiratory bronchiole to the terminal blind alveoli. Associated with a1-antitripsin deficiency
panacinar (panlobular) emphysema. The entire acinus is affected, not the entire lung. Affects lower lobes, esp bases.
in distal acinar (paraseptal) emphysema which parts of the acini are spared and which parts are affected?
central and proximal parts are spared and distal alveoli are affected. Forms along the pleura and lobule margins adjacent to fibrosis or scarring. may form cyst like structure associated with penumothorax in young adults
this form of emphysema is asymptomatic, clinically insignificant, almost always found on autopsy and irregular pattern of alveolar enlargement always is associated with scarring.
Irregular emphysema
How does emphysema appear grossly on morphology?
Large, voluminous lungs with hyperinflation (well developed pan- and centri) and bullae/blebs associated (distal acinar emphysema)
How does emphysema appear microscopically?
Abnormally large alveoli separated by thin septa, large alveoli from trapped air.
- pores of Kohn are so large that septae seem to float in alveoli
- blood vessels are compressed by emphysematous alveoli
Explain the pathogenesis of development of emphysema
Smoking and other noxious particles cause lung damage and inflammation. Factors include:
- inflammatory mediators and leukocytes (Leukotriene B4, IL8, TNF etc) –> epithelial damage and structural change
- protease- antiprotease imbalance. relative deficiency of protective antiprotease which in some are genetic in basis.
- Oxidative stress. substances from tobacco smoke, alveolar damage and inflammatory cells all produce oxidants, which may beget more tissue damage and inflammation. Proven in mouse model with NRF2 gene mutation. NRF2 target genes are all associated with smoking-related lung disease in humans.
- Infection: does not initiate it but exacerbates the disease process
The idea that proteases are important is based in part on the observation that patients with a genetic deficiency of _ have markedly enhanced tendency to develop pulmonary emphysema which is compounded by smoking.
Antiprotease a1-antitrypsin (AAT) which normally inhibits action of elastase and so without AAT elastase is unchecked and destroys the elastic tissue of the alveoli
emphysema is a condition characterized by dilation of air spaces with 1 (dec or inc) elasticity and 2 (dec or inc) compliance
- decreased
2. Increased
which type of emphysema is commonly due to smoking? due to AAT deficiency?
Smoking = Centriacinar AAT = panacinar , smoking exacerbates
what are the signs, symptoms and physical findings of emphysema?
- signs and Symptoms: dyspnea, classic pursed-lip breathing;
- Physical findings: decreased breath sounds on auscultation, increased anterior-posterior diameter (barrel chest), hyperresonant to percussion, flattened diaphgram on Xray
- decreased diffusion capacity –> increased ventilatory rate –> normal ABG
- patients will lean forward, have a prolonged expiration through pursed lips.
Pink Buffer (end stage) - impaired expiratory airflow measured through spirometry
How is emphysema treated?
- smoking cessation, ambulatory O2
- bronchodilators, inhaled steroids, oral/IV steroids and antibiotics
A 50-year-old Caucasian male presents to the Emergency Department complaining of shortness of breath and unintentional weight loss over the past several months. On physical examination, the patient appears quite thin and breathes through pursed lips. Breath sounds are decreased in all lung fields. The patient’s chest x-ray shows increased A-P diameter. Which of the following findings is expected on spirometry?
- Increased FEV1
- Decreased FEV1/FVC
- Decreased TLC
- Normal FEV1 but increased FVC
- Normal lung values
- Decreased FEV1/FVC
The patient described is suffering from Chronic Obstructive Pulmonary Disease (COPD), specifically emphysema. In emphysema, both FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) are decreased, however, FEV1 is decreased more, therefore FEV1/FVC is decreased.
A patient with a1-antitrypsin deficiency is warned by his physician that his increasing dyspnea may be worsened by his continued cigarette smoking. Which of the following factors, released by both neutrophils and alveolar macrophages, is responsible for the patient’s condition?
- Major Basic Protein
- Antibodies against alpha-3 segment of collagen IV (COL4A3)
- Mucus
- Surfactant
- Elastase
- elastase
The patient is suffering from emphysema caused by his genetic disorder, a1-antitrypsin deficiency. This condition can be worsened by smoking-mediated increased release of elastase from macrophages and neutrophils.
what causes do emphysema patients usually die of?
- coronary artery disease
- respiratory failure
- Right sided heart failure
- massive collapse of lungs secondary to pneumothorax
_ is a term used to designate dilation of alveoli in response to loss of lung substance elsewhere. It is best exemplified by hyperexpansion of residual lung parenchyma following surgical removal of a diseased lung or lobe
Compensatory hyperinflation
_ is expansion of lung because of trapped air but without septal wall destruction.
Obstructive overinflation
what are common causes of obstructive overinflation?
tumor or foreign objects, asthma with: 1) partial obstruction = ball - Valve allows air in but not out; and 2) complete obstruction + collateral air flow through pores of Kohn
Bullous emphysema is term for large subpleural blebs or bullae that can occur in any form of emphysema near apex, sometimes near TB scars. What is the occasional complication associated with it?
pneumothorax
Interstitial emphysema is entrance of air into _
connective tissue stroma of lung, mediastinum or subQ tissue
what is interstitial emphysema caused by?
alveolar tears (cough + alveolar obstruction as in empysema), punctures, or trauma or mechanical ventilation
_ is defined as persistant cough with sputum production for at least 3 months in at least 2 consecutive years, in absence of any other cause.
chronic bronchitis. common among smokers and polluted cities. Falls in one end of the sepctrum of COPD
Primary or initiating factor in the genesis of chronic bronchitis is exposure to noxious inhaled substances such as tobacco smoke and dust from grain, cotton, and silica. Explain the pathogenesis that follows
- Mucus hypersecretion (IL13, histamine) in large airways, hypertrophy of submucosal glands in trachea and bronchi –> increased goblets cells and mucous production
- Inflammation –> cellular damage involving neutrophils, lymphocytes and macrophages –> inflammation/fibrosis –> chronic airway obstruction
- Infection: does not initiate but exacerbates disease process
Explain the pathophysiological changes seen in chronic bronchitis
- imbalance or proteinase/anti-proteinases, inflammation, oxidative stress, and inhibited repair processes,
- central and peripheral airways involved
- results in hyperplasia of bronchiolar mucus glands and fibrosis of terminal bronchioles
- ciliary dysfunction
what are two most common cause of chronic bronchitis?
- smoking
- cystic fibrosis
what are some signs and symptoms of chronic bronchitis?
Symptoms: dyspnea, productive cough
PE: wheezing and crackles on auscultation, prolonged expiration, classic pursed lip breathing,
- Blue bloater (end stage): chronic alveolar hypoxia leads to pulmonary HTN, edematous due to right heart failure; cyanosis of skin
How is chronic bronchitis treated?
- conservative: smoking cessation, home O2
- Pharmacological: bronchodilators and inhaled steroids for long term maintenance; systemic steroids and abx for acute exacerbations; roflumilast for severe disease
_ is a chronic disorder of the conducting airways, usually caused by an immunological reaction, which is marked by episodic bronchoconstriction due to increased airway sensitivity to a variety of stimuli; inflammation of bronchial walls; and increased mucus secretion
asthma
_ is manifested by recurrent episodes of wheezing, breahtlessness, chest tightness and cough, particularly at nigh and/or in the early morning
asthma
what are the two categories of asthma
- Atopic : allergen sensitization and immune activation, positive family history
- Non-atopic: no evidence of allergen sensitization. Family history is less common.
In either can have diverse triggers such as infection, irritants, cold air, stress, exercise, and even drugs such as aspirin
Atopic asthma is most common type and is a classic example of _ hypersensitivity reaction
IgE-mediated (Type I)
_ can be used to diagnose actopic asthma.
high total serum IgE levels or evidence of allergen sensitization by serum radioallergosorbent tests (RAST)
How do patient’s with aspirin-sensitive asthma present?
Occur in pts with recurrent rhinitis and nasal polyps, they experience an asthmatic attack and urticaria. Attack is triggered by inhibiting COX pathway leading to rapid decrease in prostaglandin E2 which normally inhibits enzymes that generate proinflammatory mediators like leukotrienes B4, C4, D4, and E4 which are thought to be the major players in aspirin-induced asthma
Explain the pathogenesis of atopic asthma
- Caused by exaggerated TH2 responses to normally harmless environmental antigens in genetically predisposed people. TH2 secrete cytokines (IL4, IL5, IL13) and other cytokines such as IL17 and IL19 that promote inflammation and stimulate B cells to produce IgE and other Ig. –> airway dysfunction via release of potent inflammatory mediators and remodeling of airway wall –> increased local secretion of GF, induction of mucus glands hypertrophy, smooth muscle proliferation, angiogenesis, fibrosis and nerve proliferation.
Explain the acute/early response of atopic asthma
- airborne antigens react first with mast cells on epithelial surface causing an increased permeability, access to submucosal mast cells, enhanced type 1 response.
- direct stimulating of subepithelial vagal (parasympathetic) receptor resulting n constriction
- sum total in bronchoconstriction, edema, mucous secretion
Explain the late phase response in atopic asthma
- swarm of leukocytes (eosinophils, neutrophils, and more T cells (TH17)) drawn by chemotactic factors from mast cells, airway epithelium, and vascular endothelium and other leukocytes
- Eosinophils major basc protein = epithelial damage and airway constriction
What are the major mediators that which play a role in asthmatic attack
- major bronchospasm mediators such as Leukotrienes C4, D4, and E4 prolongs bronchoconstriction and increased vascular permeability and increased mucus secretion; acetylcholine which can also bronchoconstrict
- minor bronchoconstriction and vasodilators: histamine; prostaglandins D2; platelet activating factor. these factors are more important in chronic or nonallergic asthma
- unknown role but suspected: IL1, IL6, and TNF alpha are proinfllammatory cytokines
Polymorphism in what gene has the strongest and most consistent association with asthma or allergic disease?
IL13 on chromosome 5q
Polymorphism in gene encoding _ a metaloproteinase may be linked to increased proliferation of bronchial smooth muscle cell and fibroblast, thus contributing to bronchial hyperreactivity and subepithelial fibrosis
ADAM33
Increased serum levels and expression of _ are correlted with asthma severity, airway remodeling, and decreaesd pulmonary function
YKL-40, a chitinase-like glycoprotein expressed and secreted by many cells
Although infection is not a cause or trigger for asthma, URI with what virus has a 10 to 30 fold increased risk of devleoping persistent and/or severe asthma?
rihonovirus type C and RSV
A characteristic finding in sputum or bronchoalveolar lavage specimens of asthmatic patients include_
- Curschmann spirals which may result from extrusion of mucus plugs from subepithelial mucous gland ducts or bronchioles;
2) Charcot-Leyden crystals composed of eosinophil protein called galectin 10
What specific changes are taken place in “airway remodeling” as seen in asthma
- thickening of airway wall
- subbasement membrane fibrosis
- increase in size of submucosal glands and number of airway goblet cells
- hypertrophy and/or hyperplasia of bronchial wall muscle
How does a patient with asthma attack present?
cardinal signs are: chest tightness, dyspnea, wheezing and coughing (w/wo sputum production) triggered by bronchospasm that can spontaneously resolve or resolve with intervention.
- Attacks last minutes to hours
- in most severe form (status asthamaticus) where ventilatory function can be impaired (and fatal), asthma symptoms may last for hours to day and are refractory to retreatment
How is an asthma attack diagnosed?
- increaed in airflow obstruction from baseline,
- difficulty with exhalation
- peripheral blood eosinophilia and finding of eosinophils, curschman spirals, and charcot leyden crystal in sputum
_ is a disorder in which destruction of smooth muscle and elastic tissue by chronic necrotizing infections leads to permanent dilation of bronchi and bronchioles
Bronchiectasis
what are some causes of bronchietasis?
- congential or hereditary conditions including CF (secondary to infection with pseudomonas or aspergillus), intralobar sequestraiton of lung, immunodeficiency states, and primary ciliary dyskinesia and kartagener syndromes
- Infection, including necrotizingpneumonia (common are aspergillus which is common to CF or asthma pts)
- Bronchial obstruction due to tumor, foreign bodies, or mucus impaction; in each instance the bronchietasis is localized to obstructed lung segment
- Associated with other disease such as rheumatoid arthritis, SLE, IBD, COPD, postransplantation
- 1/4-1/2 of cases are idiopathic
Obstruction and infection are the major conditions associated with bronchiectasis. What are the predisposing factors that which leads to bronchiectisis?
- CF: defective ion transport leads to defective mucocilary action and airway obstruction by thick viscous secretion –> infection –> widespread damage to airway walls –> destruction of supporting smooth muscle and elastic tissue -> dilated bronchi and obliterated bronchioles. –> fibrosis (bronchiolitis obliterans)
- Primary ciliary dyskinesia: autosomal recessive with cilary dysfunction due to defects in ciliary motor proteins contributes to retention of secretion and recurrent infection –> bronchiectasis. These pts also develop Kartagener syndrome due to abnormal ciliary function which is needed for organ development in chest and abd. Kartagener syndrome is marked by situs inversus or partial lateralizing abnormality associated with bronchietasis and sinusitis
- Allergic bronchopulmonary aspergillosis occurs in pts with asthma and cystic fibrosis who develop periods oexacerbation and remission that may led to proximal bronchietasis and fibrotic lung disease. High association with aspergillus fumigatus senstization which leads to activation of TH2 and that recruits eosinophils and other leukocytes.
Explain the gross and histologic finding of bronchietecsis
Gross: lower lobes bilaterally unless caused by a focal obstruction (tumor or foreign body aspiraiton) in which case there are focal lesion; airways are dilated up to 4x, some ares look like cysts filled with pus
Histologic: acute inflammatory exudate associated with desquamination of epithelium or even ulcerations; chronic - pseudostratification and squamous metaplasia, almost always with fibrosis, organism can be cultured at any phase, often H influenze or aspergillus
How does bronchiectasis present clinically?
- severe, persistent cough; expectoration of foul smelling, sometimes bloody sputum; dyspnea nad orthopnea in severe cases; on occastion hemoptysis. paroxysms of cough are frequent when pt rises in the morning as the change in position causes collections of pus and secretion to drain into bronchi.
- Obstructive respiratoyr insuffieciency can led to marked dyspnea and cyanosis.
- due to modern therapy mortality is decreased and cor pulmonale, brain abscess, amyloidosis are less frequent complications
The classic functional abnormalities of restrictive lung disease include _
- reduction in diffusion capacity
- reduction in lung volume
- reduction in lung compliance
These eventually leads to right sided heart failure associated with cor pulmonale
_ refers to a clinicopathologic syndrome marked by progressive interstitial pulmonary fibrosis and respiratory failure
Idiopathic pulmonary fibrosis (IPF)
What environmental factors and genetic factors are associated with IPF?
- Environmental factors: smoking, metal fumes, wood dust, farming, hair dressing, and stone polishing. All these cause recurrent alveolar epithelial cell damage
- Genetic factors: Most people who smoke or have other environmental exposure do not get the disease thus indicating there is a genetic link. (A) Germline loss of function mutation in TERT and TERC which encode components of telomerase. 15% of familial IPF have telomerase gene defects and 25% of sporadic IPF are associated with abnormal telomerase shortening; (B) mutation gene for surfactant–> folding defects –> activating of unfolded protein response to type II pneumocytes –> pneumocytes more susceptible to environmental insults; (C) increased secretion of MUC5B, a mucin that make alveolar epithelial cells susceptible to injury or exaggerated downstream events leading to fibrosis
- these injuries to alveolar cells set in motion event that lead to increase local production of fibrogenic cytokines such as TGF-b
IPF is a disease of older people, rarely appearing before the age of _
50.
In the pathway to fibrosis as seen in IPF, activated fibroblasts exhibit signaling abnormalities that lead to increased signaling through which pathway?
PI3K/AKT pathway
Explain how IPF appear grossly and histologically
Gross: lungs are cobblestoned, due to retraction of scars along the interlobular septa. Cut surface shows firm, rubbery white areas of fibrosis which occur in subpleural regions along interlobular septa preferentially.
Histo: patchy interstitial fibrosis. Early: fibroblastic foci. later: honeycomb fibrosis (hyperplastic type II pneumoncytes or bronciolar epithelium)
what are the clinical signs of IPF?
- starts insidiously with gradual increasing dyspnea on exertion and dry cough. Most are 55-75 of age.
- hypoxemia, cyanosis and clubbing occur in late course
- 3 yrs survival rate
- tx: lung transplant
why is it important to distinguish a patient with nonspecific interstitial pneumonia vs interstitial pneumonia?
Nonspecific interstitial pneumonia pts have a better prognosis with proper treatment
Histologically nonspecific interstitial pneumonia is divided into cellular and fibrosing patterns. Explain the difference
Cellular: mild to moderate chronic interstitial inflammation with lymphocytes and few plasma cells in uniform or pathcy distribution
Fibrosing: diffuse or patchy interstitial fibrotic lesions of roughly same stage of development.
Clinically how to pts with nonspecific interstitial pneumonia present?
- dyspnea, cough of several months
- female in their 6th decade
- on CT: bilateral symmetric, lower lobe reticular opacities
- younger pts with cellular patterns vs fibrosing pattern have better prognosis
What are the characteristic clinical and histologic findings of cryptogenic organizing penumonia?
aka bronchiolitis obliterans organizing pneumonia (this name is nor preferred).
- Clinical: cough, dyspnea, patchy subpleural or peribronchial areas of airspace consolidation on radiograph.
- histo: polypoid plugs of loose organizing CT (Masson bodies) within alveolar ducts, alveoli, and bronchioles. CT are all same age and lung architecture is normal. No interstitial fibrosis (Note: if there is fibrosis then it’s probably due to infection or inflammatory injury of lungs and prognosis depends on underlying cause), and no honeycomb lung.
- pts recover spontaneously, tho some may need steroid for up to 6 months
what autoimmune diseases commonly have pulmonary involvement?
- Rheumatoid arthritis (RA) (30-40% have pulm involvement)
- SLE
- Scleroderma
What pulm disorders are associated with RA?
- chronic pleuritis w/wo effusion
- diffuse interstitial pneumonitis and fibrosis
- intraplulm rheumatoid nodules
- follilcular bronchiolitis
- pulm HTN
What pulm disorders are associated with scleroderma?
- diffuse interstitial fibrosis (nonspecific interstitial pattern more common)
- pleural involvement
what pulm disorders are associated with SLE
- patchy, transient parenchymal infiltrates, or occasional severe lupus pneumonitis
- pleurisy and effusion
What is Pneumoconioses defined as?
inhalation of small dust particles (coni = latin for dust)
What factors determine the development of penumoconiosis?
- amount of dust retained in lung and airways - dust concentration in air, and retainment in lung is influenced by smoking that destroys mucociliary clearance
- size, shape, and buoyancy of particles. Most dangerous size are 1-5 microns cuz these are able to reach terminal airway
- Particle solubility and physiochemical reactivity. Small particles of injurious substance with high solubility are more likely to cause acute lung injury. Larger ones resist dissolution and my persist within lung for years –>evoke fibrosing cllagenous pneumoconioses as seen in silicosis
- possible additional effects of other irritants
- substance that activate inflammasome amplify the intensity and duration of local reaction cuz they activate both innate and adaptive immune response
- Tobacco makes it all worse esp asbestos
- Genetic predisposition.
Coal worker’s pneumoconiosis ranges from asymptomatic form known as _ 1_to progressive massive fibrosis where contaminated 2 in the coal dust favor the progressive disease.
- antracosis
2. silica
Coal worker’s pneumoconiosis (CWP) ranges from asymptomatic form known as _ 1_to progressive massive fibrosis where contaminated 2 in the coal dust favor the progressive disease.
- antracosis
2. silica
How is simple coal worker’s pneumoconiosis characterized by?
Coal macules and coal nodules. Coal macules are carbon-laden macrophages; nodules also contain a delicate network of collagen fibers, upper lob es (high ventilation) and upper zone of the lower lobes.
Rheumatoid nodules in lungs can be complicated by coal worker’s penumoconiosis in a syndrome called __
Caplan’s syndrome
1-2 cm fibrotic centers is seen what form of coal worker’s pneumoconiosis?
Complicated CWP
What are clinical findings of CWP?
- usually benign causing little decrement in lung fxn.
- progressive massive fibrosis leads to pulm htn, and cor pulmonale.
- No association with lung cancer
- no susceptibility to TB
- once advanced disease is reached, no further exposure to coal dust does not improve course, like silicosis
pertinent epidemiology of silicosis include _
- workers in foundaries, sandblasting, mining industries, repair, rehabilitation or demolition of concrete
- African Americans at higher risk than whites
Explain the pathogenesis of silicosis
- crystalline form more fibrogenic such as quartz
- after inhalation its phagocytosed by macrophages –> inflammasome –> release of inflammatory mediators IL1, IL18.
Silicosis commonly found in what part of the lung?
Hilar lymph nodes and upper zones of lungs
Silicosis starts off as tiny barely palpalble pale blackened nodules in the hilar lymph nodes and upper zones of lungs, but as it progresses it forms _
Hard, collagenous scars where some can forms central softening and cavitation due to superimposed TB or ischemia.
_ is Characteristic finding on radiograph of progressive silicosis
eggshell calcification as sheets of calcification in lymph nodes.
The histologic findings of silicosis include _
central area of whorled collagen fibers with more peripheral zone of dust laden macrophages. These can be polarized to find birefringent silicate particles (silica is weakly birefringent)
Explain the clinical course of silicosis
- on radiograph: fine nodularity in upper zone.
- pulm fxn either normal or only moderately affected early on with no SOB until progressive massive fibrosis supervenes.
- impair macrophages function –> increased susceptibility to TB unlike CWP
- DOUBLES THE RISK OF DEVELOPING LUNG CANCER
Localized fibrous plaques or rarely diffuse pleural fibrosis, recurrent pleural effusion, parenchymal interstitial fibrosis, lung carcinoma, mesothelioma, laryngeal, ovarian cancers, all have been implicated to chronic exposure to _
asbestos
Asbestos occur in two forms serpentine and amphibole. 1) Which one is responsible for 90% of exposure as it’s used in industry? and 2) which one is less common but more pathogenic in that it induces mesothelioma.
- Serpentine - more likely to cleared by mucociliary action
- Amphibole - small enough to reach lung instersitium quickly by escaping mucociliary action
Note: both are equally fibrogenic, nonetheless
Explain how smoking and asbestos exposure are synergistic
- both are oncogenic, mediated by free radicals generated by both
- The carcinogen in tobacco smoke onto asbestos fibers is the basis for synergy for developing lung carcinoma.
- smoking destroys mucociliary action thus making asbestos easier to make it down to lung parenchyma.
- risk of carcinoma is increased by 55 fold with both
Explain how injury occurs with asbestos exposure.
Once phagocytosed by macrohagess, asbestos fibers activate inflammasome and stimulate and release proinflammatory factors and fibrogenic mediators
- Starts in bifurcation of small airways and ducts where they land and penetrate.
- macrophages and alveolar/interstitial macrophages tries to clear the fibers. long term exposure leads to persistent release of mediators, ROS, protease, cytokines, growth factors –> interstitial pulmonary inflammation and interstitial fibrosis
how is diffuse pulmonary interstitial fibrosis from asbestos distinguished from fibrosis from other pneumoconiosis?
Presence of asbestos bodies which are golden brown, fusiform or beaded rods with translucent center and consistent of asbestos fibers coated with an iron-containing proteinaceous material
- Ferruginous bodies may be also seen (iron-coated protein comlex)
_ are the most common manifestation of asbestos exposure, and are well circumscribed plaques of dense collagen found on anterior and posterolateral aspect of parietal pleura and over domes of diaphragm.
Pleural plaques. –> restrictive lung disease -= normal FEV1/FVC ratio and low FVC
Asbestosis affects which parts of the lung most commonly?
Lower lobes including entire respiratory unit
What drugs are commonly known to cause fibrosis and drug induced lung disease?
- bleomycin (chemo)
- amiodarone —> pneumonitis
- illict IV drugs
Radiation induced lung disease is pretty common can manifest as acute radiation pneumonitis (lymphocytic alveolitis or hypersensitivity pneumonitis) 1-6 months after irradiation, manifested with fever, dyspnea out of proportion to the volume of lung, pleural effusion and infiltrates that usually corresponds to area of irradiation. Presence of what cells are characteristic of radiation damage?
Atypia of hyperplastic type II cells and fibroblasts. Epithelial cell atypia and form cells within vessel walls in particular are characteristic.
Sarcoidosis presents in many clinical patterns, but most common, 90% of cases, occur where?
bilateral hilar lymphadenopathy or lung involvement
Pertinent epidemiology of sarcoidosis include _
- female adults younger than 40
- Southeast U.S.
- Blacks 10x more than whites
- rate in chinese and southeast asians.
What kind of lung diseases does sarcoidosis cause?
restrictive most common. Obstructive or mixed pattern is also seen
Sarcoidosis _1_mediated disease, particularly 2 T cells resulting ratio of _3 / _ rraning from 5:1 to 15:1. Leads to increased levels of T-cell derived TH1 cytokines such as 4 and 4 which may be responsible for T cell expansion and macrophage activation. Impaired of 5 cell function is also noted
- T cell
- CD4
- CD4/CD8.
- IL2, IFNy
- Dendritic
What genetic influence are seen in development of sarcoidosis?
HLA genotypes (e..g HLA-A1 and HLA-B8)
Morphologically in sarcoidosis, nonnecrotizing granulomas composed of aggregates of epitheliod macrophages is common, although central necrosis is unusual. Additionally, laminated concretions composed of calcium and protein known as _ 1_and stellate inclusion known as 2 are found within giant cells in 60% of cases.
- Schaumann bodies
2. Asteroid bodies
Sarcoidosis is discovered incidentally on radiograph. Initially, most often patient medical attention due to what symptoms?
- respiratory symptoms such as SOB, cough, chest pain, hemoptysis or constitutional signs like fever, fatigue, wt loss, anorexia night sweats.
What are symptoms of sarcoidosis
- Cough, fever, malaise, arthritis main in ankle and legs.
- can be GRUELING (Granulomas, Rheumatoid arthritis, Uveitis, Erythema nodosum, Lymphadenopathy, Interstitial fibrosis, Negative TB, Gammaglobuinemia)
Physical findings of sarcoidosis include _
- Skin lesions: nodular granulomatous lesions, facial rash, erthyma nodosum, eye lesions (uveitis), enlarged salivary and lacrimal glands
A 31 year-old African-American female presents with a painful shin nodules, uveitis, and calcified hilar lymph nodes. A transbronchial biopsy of the lung would most likely show which of the following histologies?
- Inflammation, fibrosis and cyst formation that is most prominent in subpleural regions
- Silica particles (birefringent) surrounded by collagen
- Golden-brown fusiform rods
- Patchy interstitial lymphoid infiltrate into walls of alveolar units
- Non-caseating granulomas
- Non-caseating granulomas.
The clinical presentation in this vignette is most likely sarcoidosis. Biopsy of the lung in this patient would show non-caseating granulomas.
A 38-year-old African American female presents to her primary care physician with uveitis, cough, and arthralgias in her ankles and legs. Bloodwork reveals elevated angiotensin converting enzyme levels, and skin PPD testing shows no observable induration after 48 hours. The patient demonstrates reduced FEV1 and FVC upon spirometry. FEV1/FVC is 85%. Which of the following would you expect to see upon chest X-ray:
- Enlarged hilar lymph nodes
- Kerley B Lines
- Bilateral diaphragmatic elevation.
- Pleural effusion
- Fluid in alveolar walls
- Enlarged hilar lymph nodes
The clinical presentation is consistent with sarcoidosis. Enlarged hilar lymph nodes are commonly seen on chest radiographs of patients with sarcoidosis.
what findings suggests that hypersensitivity pneumonitis is an immunologically mediate disease
- increased levels of proinflammatory chemokines such as protein 1a and IL8, CD4, CD8, ab against causative agents, complement and Ig within vessel walls, presence of noncreasting granulomas (Tcell mediated - Type IV hypersenstivity)
what are the clinical features of hypersensitivity pneumonitis?
- acute attack followed by recurring episodes of fever, dyspnea, cough, and leukocytosis.
- Micronodular interstitial infiltrates on chest radiograph, and pulmnary fxn show acute restrictive disorder
- symptoms appear within 4-6 and lasts for 12hrs to several days
- chronic exposure –> progressive resp failure, dyspnea, and cyanosis decreased in TLC and compliance
What is pulmonary eosinophilia?
- pathologic pulmonary entities characterized by an infiltration of eosinophils, recruited in part by elevated alveolar levels of eosinophils attracts such as IL5
What are the different types of pulmonary eosinophilia?
- Acute eosinophilic pneumonia with respiratory failure: rapid onset of fever, dyspnea, hypoxemic respiratory failure. Responds to corticosteroids
- Secondary eosinophiliaphilic pneumonia: occur in parasitic, fungal, andbacterial infeciton; in hypersensitivity, pneumonitis, drug allergies; asthma, aspergillosis, vasculitis (churg-strauss)
- Idiopathic chronic eosinophilic pneumonia: focal area of cellular consolidation around periphery lung fields. aggreagates of lymphocytes and eosinophils in both septal walls and alveolar spaces. Cough, fever, night sweats, dyspnea and wt loss. Responds to corticosteroid therapy.
_ is characterized by large collection of macrophages in airspaces in a current or former smoker,
Desquamative interstitial pneumonia
Morphologically, the characteristic finding of desquamative interstitial pneumonia includes _
accumulation of large number of macrophages with abundant cytoplasm containing dusty brown pigment (smokers’ macrophages)
How does desquamative interstitial pneumonia present?
- presents in 4th or 5th decade of both men and women
- dyspnea, cough, over weeks to months, often associated with clubbing of digits
- reduction of diffusing capacity of CO2.
- excellent response to steroid therapy and cessation of smoking
_ is marked by chronic inflammation and peribronchiolar fibrosis, common histologic lesion in cigarette smokers characterized by presence of pigmented intraluminal macrophages within 1st and 2nd order respiratory bronchioles. Morphologically smoker’s macrophages are seen.
Respiratory bronchiolitis-associated interstitial lung disease. Symptoms: gradual onset of dyspnea and cough
Pulmonary Langerhan cell histiocytosis is a rare disease characterized by focal collections of Langerhans cells and sometimes with eosinophils, seen in young smokers, with cystic and nodular abnormalties seen on imaging. To diagnose, they can be tested for cluster of differentiations and ribosome. What CD are they positive for?
Positive for CD1a, and CD207 (langerin). negative for CD68. Also positive for S100.
Some have activating mutations in serine/threonine kinase BRAF.
Pulmonary alveolar proteinosis (PAP) is a rare disease caused by defects related to _
granulocyte-macrophage colony-stimulating factor (GM-CSF) or pulmonary macrophage dysfunction that results in accumulation for surfactant in intra-alveolar and bronchiolar spaces. Presents as autoimmune PAP, secondary PAP, and hereditary PAP (mutation disrupt genes involved in GM-CSF signaling).
Autoimmune PAP is caused by circulating neutralizing antibodies specific for _
GM-CSF. Occurs primarily in adults, 90% of all cases of PAP, with no family predisposition.
Secondary PAP is associated with diverse disease such as 1 and is speculated that is due to inadequate clearance of 2
- hematopoietic disorders, malignancies, immunodeficiency disorders, lysinuric protein intolerance and acute silicosis and others.
- surfactant from alveolar spacs
what are the morphologic findings of PAP?
- homogeneous, granular precipitate containing surfactant proteins within alveoli, causing focal to confluent consolidation - increase in size and wt of lung
what is the standard of care for PAP?
- whole long lavage.
- GM-CSF therapy effective in more than 1/2 pts with autoimmune PAP
what mutations are implicated in surfactant dysfunction disorders?
- ATP-binding cassette protein member 3 (ABCA3) - most common mutation in this disease. Presents first few months of life with rapidly progressive resp failure and death
- Surfactant protein C - second most common. autosomal dominant
- Surfactant protein B: least common -occur in infants. infants are usually full term and rapidly develops progressive respiratory distress shortly after birth. death 3-6 monts
Small lamellar bodies with electron dense cores are diagnostic for which mutational form of surfactant dysfunction disorder?
ABCA3
what’s defined as pulmonary HTN?
Pulmonary artery pressure greater than 25mmHg or greater than 30 mmHg during exercise. (normal is 10-14)
pulmonary HTN is classified into what 5 groups according to WHO
- pulm artery htn involving small pulm muscular arteries
- pulm htn secondary to left sided failure
- pulm htn stemming from lung parenchymal disease or hypoxemia
- chronic thromboembolic pul htn
- pulm htn of multifactorial basis
what are common causes of pulm htn?
- Chronic obstructive or interstitial lung disease (WHO gr 3) –> inc resistance –> inc pulm BP
- Antecedent congenital or acquired heart disease, e.g. ASD, VSD (WHO gr 2)
- Recurrent thromboemboli (WHO gr 4): reduces cross-sectional area of pulm vasculature –> inc resistance
- Autoimmune disease (gr 1) esp SLE -> inc resistance
- Obstructive sleep apnea (gr 3) is a common disorder that is associated with obesity and hypoxemia.
In the pathogenesis of pulm htn, idopathic or familial pulm artery hypertention has been noted. Mutation in _ gene predispose to abnormal vasculature, increasing the risk of developing pulm HTN
BMPR2, which is a cell surface protein belonging to TGF-b receptor superfamily, which binds to a variety of cytokines, including TGF-b, BMP, activin, and inhibin. Normally acts to inhibit smooth muscle growth, mutated gene leads to increased secretion of vasoconstrictors and decrease secretion of vasodilators.
A 73-year-old female is hospitalized following a pelvic fracture. She undergoes surgical repair without complication. Four days into her hospital stay, she develops acute dyspnea and chest pain accompanied by oxyhemoglobin desaturation. Which of the following arterial blood gas values is the patient most likely to have?
- pH 7.5, PaO2 60, PaCO2 30, HCO3 22
- pH 7.3, PaO2 60, PaCO2 30, HCO3 20
- pH 7.5, PaO2 60, PaCO2 50, HCO3 28
- pH 7.3, PaO2 60, PaCO2 50, HCO3 24
- pH 7.4, PaO2 60, PaCO2 40, HCO3 24
- pH 7.5, PaO2 60, PaCO2 30, HCO3 22
The patient in this vignette most likely has a pulmonary embolism (PE) secondary to a deep vein thrombosis (DVT). Classically, a PE results in a hypoxic, respiratory alkalosis.
A 68-year-old female presents to the emergency room with acute onset of dyspnea and hemoptysis. Her past medical history is unremarkable and she has had no prior surgeries. A ventilation-perfusion scan demonstrates a large perfusion defect that is not matched by a ventilation defect in the left lower lobe. Which of the following would you also expect to find in this patient:
- Pleuritic chest pain
- Bradycardia
- Aortic dilation
- Claudication
- Increased inspiratory capacity
- Pleuritic chest pain
The patient’s symptoms and ventilation-perfusion scan results are consistent with pulmonary embolism (PE). Pleuritic chest pain is a common presenting symptom.
As part of diffuse pulmonary hemorrhage syndrome, In goodpasture syndrome , circulating antibodies (against a3 chain of collagen IV) initiate inflammatory destruction of _
pulmonary alveoli giving rise of necrotizing hemorrhagic interstitial pneumonitis
Most cases occur in male teens or in their 20s who smoke. Linked to HLA-DRB1*1501 and *1502
10 yr old boy presents with sudden onset of productive cough and hemoptysis. Lab revealed he is anaemic and on imaging diffuse pulmonary infiltration were shown. NO other abnormalities were found. Pt responded well to immunosuppression therapy with prednisone and azathioprine. What is the likely diagnosis
Idiopathic pulmonary hemosiderosis.
A 62-year-old Caucasian male presents to your office with hemoptysis and hematuria. On physical exam you note a saddle nose deformity. Laboratory results show an elevated level of cytoplasmic antineutrophil cytoplasmic antibody. Which of the following interventions is most appropriate for this patient?
- Smoking cessation
- IV immunoglobulin
- Corticosteroids
- Isoniazid
- Discontinuation of ibuprofen
- Corticosteroids
This patient’s presentation is consistent with granulomatosis with polyangiitis (Wegener’s granulomatosis). GPA is appropriately treated with cyclophosphamide and corticosteroids.
A 45-year-old man is brought to the emergency room by his wife who reported that he coughed up blood earlier that morning. He has had a chronic fever, weight loss, and blood in his urine over the past couple of weeks, but refused to see a doctor until now. Upon work up, it was determined that an autoimmune disorder of unknown origin that causes inflammation of the blood vessels
characterized by
focal necrotizing vasculitis
necrotizing granulomas in the lung and upper airway. In making this diagnosis, what is the best location for biopsy?
Transbronchial lung biopsy
Pt has polyangiitis with granulomatosis
A 55-year-old male presents to his primary care physician complaining of bloody nasal discharge and hemoptysis. His past medical history is notable for hypertension. Medications include metoprolol and amlodipine. Physical examination is notable for oral ulcers and inflamed conjunctiva. Serum creatinine is 3 mg/dL. Creatinine was 0.95 mg/dL during an office visit one year ago. IF shows the results of immunostaining for C-ANCA. Which of the following is the most likely diagnosis?
- Microscopic polyangiitis
- Polyarteritis nodosa
- Takayasu’s arteritis
- Giant cell arteritis
- Granulomatosis with polyanginitis (formerly Wegener’s granulomatosis)
- Granulomatosis with polyanginitis (formerly Wegener’s granulomatosis)
The patient’s symptoms, including upper respiratory symptoms, evidence of pulmonary involvement via hemoptysis, and renal failure as indicated by a severe rise in creatinine, are consistent with granulomatosis with polyanginitis (GPA).
Germline mutation in MyD88 is associated with _
destructive bacterial (pneumococcal) pneumonias. MyD88 is an adaptor for several TLRs that is important for activation of transcription factor NFkB
Cell-mediated immune defects (congenital and acquired) leads to increased infection with what kind of bacteria?
Intracellular microbes such as mycobacteria and herpesviruses as well as microorganisms of very low virulence such as pneumocystis jiroveci
What are some biomarkers that which can distinguish between bacterial vs viral pneumonia?
- CRP
- procalcitonin
both of which are elevated in bacterial more than in viral infections
what is the MOST COMMON causative agent of community-acquired acute pneumonia?
Streptococcus pneumoniae
What features, seen on culture, supports the diagnosis of streptococcus pneumonia?
presence of many neutrophils containing typical gram+ lancet-shaped diplococci.
Note: s pneumoniae is part of normal flora in 20% of pts thus false-positive result can be obtained
What groups of pts are high risk of community-acquired pneumonia and what can reduce the risk?
- extremes of age,
- Chronic diseases (CHF, COPD, diabetes)
- congenital or acquired immune deficiencies,
- absent spleen (sickle cell disease or psotsplenectomy puts pts at higher risk of encapsulated bacteriaal infection such pneumonoccus)
Pneumococcal vaccines for high risk pt population
_ is pleomorphic, gram- organism that occurs encapsulated or nonencapuslated and has six serotypes of the encapsulated form of which type b is the MOST virulent. Do vaccines exist?
Haemophilus influenze.
Yes. Common cause of suppurative meningitis in kids up to 5 yrs before the development of a vaccine.
While the encapsulated form of H. influenzae is more virulent and can cause pneumonia, nonencapsulated form is less virulent and can cause infection of _. What pt population is at high risk?
Upper respiratory tract, otitis media, sinusitis, bronchopneumonia. Neonates, kids with comorbidities such as prematurity, malignancy, and immunodeficiencies are at high risk.
Aside from pnemonia, and URI issues, what other illnesses is H. influenze associated with?
- acute, purulent conjunctivitis in kids
- predisposed older pts can get septicemia, endocarditis, pylonephritis, cholescystitis, and supppurative arthritis.
- exacerbation of COPD
Along with s. pneumoniae, and H. influenzae _ constitutes one of the three most common causes of otitis media in children?
Moraxella catarrhalis
What is the second most common cause of acute exacerbation of COPD?
Moraxella catarrhalis. gram(-) cocci
_ is an important cause of hospital-acquired pneumonia and is an important cause of secondary bacterial pneumonia in kids and healthy adults following an URI.
Staphylococcus aureus. Associated with high incidence of complication such as lung abscess and emphysema.
_ is the most frequent cause of gram- rod bacterial pneumonia. Commonly afflicts debiliated and malnoursihed, and chronic alcohollics. What is the characteristic sputum finding?
Klebsiella pneumoniae. Thick, mucoid, gelatinous (red jelly) often blood tinged, sputum cuz organism produces an abundant viscid capsular polysach, which the pt may have difficulty expectorating.
Psudeomonas aeruginosa commonly causes hospital-acquired infections, but related to the respiratory commonly seen what pt population?
cystic fibrosis and immunocompromised pts who are neutropenic. This bug has the propensity to invade blood vessels with consequent extrapulmonary spread –> psudomonas speticemia
For Legionella pneumoophila commonly causes pontiac fever, a self-limited URI, but can also cause pneumonia. Explain the following:
A. What environment does it flourish
B. Mode of transmission
C. What pt population legionella pneumonia is commonly seen in
D. Mortality rate in immunosuppressed pt
E. How is it diagnosed?
A. artifical acquatic environment such as water cooling towers and tubing system of waster supplies.
B. Either inhalation of aerosolized organisms or aspiration of contaminated drinking water
C. pts with predisposing conditions such as cardiac, renal, immunologic, or hematologic disease, and pts with organ transplant
D. 50%
E. Legionella antigens in urine or by a positive fluorescent antibody test on sputum. Culture with silver stain is cold standard
What kind of environmental is mycoplasma pneumoniae acquired from?
closed communities such as schools, military camps, prisons
When it comes to treatment pneumonia, from a clinical standpoint, what two factors are most important?
- identification of causative agent
2. determination of extend of disease
Morphologically, pneumonia has what two distinct gross anatomic patterns that represent a possible continuum?/
- Bronchopneumonia = extremely old or extremely young
2. Lobar pneumonia = previously healthy teens to adults
what the gross morphological/histological findings of bronchopneumonia?
- patchy consolidation of lung, conslidation areas of acute supparative inflammation without resolution often with fibrotic granulation tissue.
- Grossly appears dry, granular, grey to yellow, poorly delinated areas of lung
- histologically: supparative, neutrophil-ric exudate that fills air spaces
What are the morphological/histological findings of lobar pneumonia?
- fibrinosupparative consolidation of a large portion of a lobe or an entire lobe.
- has 4 stages all with neutrophils involved: 1) Congestion = vascular engorgement , intra-alveolar fluid with few neutrophils in a grossly heavy, boggy, and red lung; 2) Red hepatization = intra-alveolar fluid- mass of RBC, neutrophils, and fibrin with a gross distinctly red, firm, and airless lung (looks like a liver); 3) Grey hepatization = resolution of RBCs, stealing red color, but leaving fibrin, turning the red lung grey. neutrophils predominate; 4) resolution = fibrin+fluid is either organized (fibrinous) or removed by macrophages resulting in a contracted or normal lung. resolution is often complete back to pristine lung with modern abx
what complications are associated with pneumonia?
- tissue destruction and necrosis causing abscess formation (esp common with type 3 pneumonococci or klebsiella infections);
- spread of infection to pleural cavity causing intrapleural fibrinosuppurative reaction known as empyema;
- bacteremic dissemination to heart valves, pericardium, brain, kidneys, spleen, or joints causing metastatic abscess, endocarditis, meningitis, or suppurative arthritis
Explain the clinical course of pneumonia
- abrupt onset high fever, shaking chills, cough productive of sputum
- con induce fibrinosupparative pleuritis = pleuritic chest pain friction rub
- Xray shows: a well-circumscribed radio-opaque lobe (lobar pneumonia) or patchy infiltrates throughout lung field (bronchopneumonia)
- with abx, disease is controlled, and often fatalities are attributed to complications such as empyema, pleuritis, septicemia
which influenza virus type infects humans and are major cause of pandemic and epidemic influenza infections?
Type A
_ and _ are components of influenza virus envelope which consissts of lipid bilayer.
Hemogglutinin (H1-H3); Neuromindase (N1, N2)
_ is component of influenza virus that seves to attach the virus to it’s cellular target via sialic acid residues onsurface polysaccharides
Hemogllutinin
_ is component of influenza virus that facilitates release of newly formed virions that are budding from infected cells by cleaving sialic acid residues.
Neurominidase
Explain the flu viral genome and what factor determines the virus type
Composed of 8 single-stranded RNA each encoding one or more proteins. The RNA are packed into helices by nucleoprotiens that determine the virus type A, B or C
Epidemic of influenza are caused by spontaneous mutation that alter _
antigenic epitopes on viral hemagllutinin and neuromindase proteins (antigenic drift)
what causes a flu pandemic?
Antigenic shift. Both the hemagglutinin and neuromindase genes are replaced through recombination with animal influenza viruses
Control of viral infection relies on several host mechanism. The resence of viral products induces innate immune responses in fected cells such as production of 1. These mediators upregulate the expression of 2 gene which encodes a GTPase that interferes with flu gene transcription and viral replication. Cellular response is eventually augmented by development of antibody response to the viral 3 proteins
- alpha and beta interferon
- MX1
- Hemaglutinin and neurominidase
The avian flu is associated with what strain type?
H5N1
_ is a paramyxovirus that causes upper and lower respiratory infections commonly seen in young kids, elderly, and immunocompromised. Signs and symptoms are similar to RSV and often mistaken for flu. Severe infections can cause bronchiolitis and pneumonia
Human metapneumovirus (MPV)
What is the only antiviral treatment available for human MPV?
ribavirin
Severe acute respiratory syndrome that which first appeared in 2002 is caused by what virus?
Coronavirus
Many upper respiratory infections are caused by coronavirus, so what makes SARS special?
It was caused by a new coronavirus (great example of sudden emergence of a new infectious agent), that infected lower respiratory tract and spread throughout the body
What are the most common health care-associated pneumonia
Methicilin-resistant staphylococcus aureus and P. aeroginosa. these have higher mortality than those with communnity acquired pneumonia
what are most common hospital acquired pneumonia?
gram(+) cocci (mainly s. aureus and s. pneumonia) and gram)-) rods (enterobacteriaeceae and psudomonas species)
- seen in pts with prolonged abx use, immunosuppression, ventilator, or indwelling catheters
What are some causative agents of atypical “walking” pneumonia?
- Viruses such as influenza A and B; RSV; adenovirus; rhinovirus
- Mycoplasma (common in adult)
- chlamydia
Explain how atypical pneumonias appear morphologically/histologically
Gross: variable = uni/bi lateral, pathyc/total lobe, upper/lower lobes. Aeas affected as red-blue, congested and subcrepitant. Pleuritis and pleural effusion are rare
Histo: predominantly interstitial inflammation with monocytes. Intral-alveolar exudate is possible but not common–results from diffuse alveolar damage showing pink hyaline membrane as seen in ARDs
How do atypical walking pneumonia pt usually present?
- low fever, headaches, muscle aches
- recent hx of URI + a cough w/o sputum
which pts are risk of aspiration pneumonia? and how critical is this type of pneumonia?
Pts with an impaired gag and/or swallowing reflex inhale gastric contents producing both a chemical irritant (gastric acid/decaying food) and a bacterial infection (flora) –> necrotizing
- typically follows a fulminant course leading to dead.
- those who survive will have lung abscesses (local suppurative process that produces necrosis of lung tissue)
what organism commonly results in lung abscess?
aerobic and anaerobic streptococcis, S. aureus, and other gram(-) agents
Anaerobic organisms which are normally found in oral cavity, are commonly cultured in lung abscesses. Of these, 60% of cases involve what organisms?
- Bacteroides, fusobacterium and peptococcus species
What are some common ways that with lung absecss causative agents can be introduced to the lung?
- Aspiration of infective material (most common) (seen in acute alcoholism, coma, anesthesia, sinusitis, gingivodental sepsis, debilitation of cough reflex)
- Antecedent primary lung infection (commonly s. aureus, k. pneumoniae and type 3 pneumonoccucus). transplant and other immunosuppressed are at risk)
- Septic embolism
- Neoplasia (postobstructive pneumonia)
- Other: direct traumatic penetration of lungs; spread of infection from other organs, hematogenous seeding etc
What is primary cryptogenic lung abscesses?
presence of lung abscess when all known causes of lung abscess formation have been excluded and no discernible basis for the abscess formation can be identified.
Pulmonary abscesses due to aspiration are more common on which lung?
Right (anatomy 101)
explain the clinical course of aspiration pneumonia
- much like bronchiectasis
- cough, fever, copious amounts of foul-smelling purulent or sanguineous sputum
- chest pain and wit loss is common
- flubbing of fingers and toes within few weeks
- with antimicrobial therapy most resolve leaving behind a scar
- complications include: extension to pleural cavity, hemorrhage, development of brain abscesses or meningitis from septic emboli, and secondarily amyloidosis type AA.
Chronic pneumonia is most often a localized lesion in immunocompetent with with granulomatous inflammatory reaction caused by _ and _
Bacteria such as tuberculosis; or fungi such as histoplasma capsulatum
For histoplasmosis explain the following: A. Geological location where it's common B. Clinical findings C. Pathogenesis D. Morphology E. Types
A. Ohio/mississippi valley or Spelunking w/ exposure to bats or bird droppings
B. Similar to TB, but asymptomatic in most cases. Coin lesions on xray. secondary lung disease in apices with cough, fever, night sweats, wt loss.
C. inhaled mold form (microcondidia) from bat or bird droppings; transforms into yeast form and is phagocytized by macrophages, macrophages secrete TNF to recruit and stimulate other macrophage to kill histoplasma. Inhibits oxidative burst and grows intracellularly with eventual lysis.
D. Epithelioid granulomas in immunocompromised with coagulative necrosis that produce large areas of consolidation. Healed regions show fibrosis and concentric calcification (tree bark lesions). Histo: presence of methenamine silver strained organism
E. 1. Primary and chronic histoplasmosis grey-white granulomas, cough, fever, night sweats, wt loss with calcfication; 2. Disseminated histoplasmosis = no epithelioid granulomas, with focal accumulation of monocytes filled with organisms throughout body
Blastomycosis presents in what three clinical forms?
- Pulmonary blastomycosis
- Disseminated blastomycosis
- Primary cutaneous from
How does pulmonary blastomycosis present?
Recent visit to Beaver dams (rotting wood) reveals Broad, Based Budding Yeasts on histology that evades phagocytosis and recruits neutrophils.
Clinically, abrupt illness with productive cough, headache, chest pain, wt loss, fever, abd pain, night sweats, chills and anorexia.
how does blastomycosis appear on chest radiograph
lobar consolidation, multilobar infiltrates, perihiblar infiltrates, multiple nodules, or miliary infiltrates
True or false: Almost everyone who inhales spores of coccidoidies immitis become infected and develop a delayed-type hypersensitivity rxn.
True. Infact 80% of people in endmeic areas of SW and Western US and Mexico have positive skin test rxn.
What is a possible reason for the infectivity of C. immitis?
infective arthroconidia, when ingested by alveolar macrophages, block fusion of phagosome and lysosome (thus resist intracellular killing) and reproduce intracellularly within a spherule that ruptures releasing infectious organisms and eosinophilia.
How do pts with coccidiomycosis present?
Most are asymptomatic. Some get lung lesion, fever, cough, chest pain, erythema nodosum (San Juaquin fever)
- recent travels to southwestern US, deserts etc
what kind of lung lesions are seen in coccidiomycosis?
Granulomatous lesions such as in TB or histoplasmosis.
In an immunocompromised host, pathogens are implicated in pneumonia?
- Bacteria (p. aeroginosa, mycobacterium sp., L. pneumonphila, and listeria monocytogenes),
- Virus (CMV, herpes,
- Fungi (P. jiroveci, candida, aspergillus, phycomycetes, and cryptococus neoformans)
An untreated HIV pts is hospitalized with pneumonia in a critical condition. what is the most common/ likely causative agent?
S. Pneumoniae, S. aureus, H. influenzae and gram(-) rods.
While opportunistic infections are common, however, most severe pulmonary infections in HIV pts are those caused by the ones listed above. Bacterial pneumonias in HIV are more common, more serious and more often associated with bacteremia than those without HIV
For each of the CD4 counts of an HIV pts, indicate what agents are likely the cause of pneumonia:
A. >200
B. <200
C. >50
A. bacterial and tubercular infections
B. Pneumocystis pneumonia
C. CMV, fungal, and mycobacterium avium
what are some lung diseases that warrents a lung transplant?
- end stage emphysema
- idiopathic pulm fibrosis
- CF
- idiopathic/familial pulmonary arterial htn
In a lung transplant, at what week/month do most infections occur?
3-12th month after transplant
What drug can be given prophylatically to reduce risk of CMV infection? to reduce pneumocystis jiroveci infection?
Ganciclovir for CMV
Bactrim for jiroveci
A 2 months post-lung transplant pt presents with fever, dyspnea, cough and on imaging shows radiologic infiltrates. What procedure can be performed to accurately diagnose the pts’ symptoms?
Pt’s symptoms are those of acute rejection. Transbronchial biopsy must be performed to diagnose rejection, since those symptoms are similar to infection
what is the major morphologic finding that correlates to chronic rejection?
Bronchiolitis obliterans, partial or complete occlusion of small airways by fibrosis with or without active inflammation. Can’t be reversed with tx. Common complication include accelerated pulm arteriosclerosis in graft, and B cell lymphoma. 1 yr survival rate is 79%, 5 yr is 50% and 10yrs is 30%
Squamous cell carcinoma of the lung is highly associated with tobacco smoking and also harbors diverse genetic aberration involving chromosome deletions involving tumor suppressor loci. Losses of what loci/gene are known as early events in tumor evolution
3p, 9p (site of CDKN2A gene), and 17p (site of TP53 gene).
Squamous cell carcinoma show the highest frequency of TP53 mutations of all histologic types of lung cancinoma. 10% of the time p50 protein overexpression is also an early event.
- RB loss is seen in 15%
- p16, product of CDKN2A gene is seen in 65% of tumors
- recent discoveries show FGFR1 amplification
Small cell carcinoma shows the strongest association with smoking and subsequent gene mutations. What genetic mutations associated with small cell carcinoma?
- LOF aberration involving TP53 (75-90%)
- LOF of RB (almost 100%)
- Chromosome 3p deletion
- MYC amplification
What genetic mutations are seen in adenocarcinoma of the lung?
- gain of function mutations involving EGFR, ALK, ROS, MET and RET
- KRAS (tumors without TK gene mutations)
What lung cancer is most common in never smokers?
Adenocarcinoma. More common in women.
- More likely to have EGFR mutations and almost none have KRAS mutation
What are the four most common types of lung cancers?
- Adenocarcinoma (38%)
- Squamous cell carcinoma (20%)
- Small cell carcinoma (14%)
- Large cell carcinoma (3%)
- Other (25%)
What are the four types of morphologic precursor epithelial neoplastic lesions seen in lung?
- squamous dysplasia and carcioma in situ
- Atypical adenomatous hyperplasia
- Adenocarcinoma in situ
- Diffuse idiopathic pulmonary neuroendocrine
For each description/subtype, classify the lung tumors classification it is associated with
A. Papillary, clear cell, small cell, basoloid
B. Combined small-cell carcinoma
C. Minimally invasive adenocarcinoma (non mucinous, mucnous), lepidic, acinar; papillary, solid, mucinous adenocarcinoma
D. Large-cell neuroendocrine carcinoma
A. Squamous cell carcinoma
B. Small-cell carcinoma
C. Adenocarcinoma
D. Large cell carcinoma
More commonly Adenocarcinomas arise in which part of the lung?
peripheral lung. Compared to squamous cell.
Squamous cell carcinoma arise commonly in what part of the lung?
central/hilar region
_ are small lesions (less than 5mm) charactrized by dysplastic neumocytes lining alveolar walls that are mildly fibrotic.
Atypical adenomatous hyperplasia
_ is less then 3cm and is composed of entirely of dysplastic cells growing along preexisting alveolar septae.
Adenocarcarinoma in situ
_ is an invasive mmaligant epithelial tumor with galndular differentiation or mucin production by tumor cells. Can be seen as acinar, lepidic, papillary, micropapillary, and solid with mucin formation.
Adenocarcinoma. Located more on the periphary
this type of tumor, there are lepidic pattern of spread in which the tumor cells crawl along normal-appearing alveolar septae and these tumors have scarring and a peripheral lepidic growth pattern called 1
Being described is a adenocarcinoma.
1= microinvasive adenocarcinoma. these have better outcome then invasive carcinoma of the same size
_ adenocarcinoma tend to spread aerogenously, forming satellite tumors.. can be present as single of multiple nodules resemblling lobar pneumonia
Mucinous adenocarcinoma. Less likely to be corrected with surgery
These tumors start off as squamous metaplasia or dysplasia and form carcinoma in situ, and these tumors are commonly found in men and strongly associated with smoking
Squamous cell carcinoma. Can grow exophytically into bronchial lumen and as it grows it can obstruct lumen leading to distal atelectasis and infection.
Can also penetrate wall of bronchus and infilrtate along peribronchial tissues
- can grow as a cauliflower like intraparenchymal mass
Histologically squamous cell carcinomas are charcterized by presence of _
keratinization and/or intercellular bridges
_ carcinoma are almost always fatal as they are extremely aggressive and metastasize widely. Has a strong association with smoking (99% of cases are smokers)
Small cell carcinoma
The cells of these carcinoma are round, oval, or spindle shaped with prominent nuclear molding. They have scant cytoplasm, ill-defined cell borders, finely granular nuclear chromoatin (salt and pepper pattern), and no or inconspicuous nucleoli.
Small cell carcinoma
Which lung cancer is MOST commonly associated with ectopic hormone production?
Small cell carcinoma
The occurrence of neurosecretory granules, expression of neuroendocrine markers such as chromogranin, synptophysin, and CD57 suggests that small cell carcinoma are _ cell type in origin
neuroendocrine, which are present in lining of bronchial epithelium
In histochemistry of small cell carcinoma, there are high levels of what protein?
antiapoptotic protein (in 90% of tumor)
_ is an undifferentiated malignant epithelial tumors. Tumor marker tests will be negative for TTF-1, naspin-A, p63, p40. Most commonly metastases to the bronchial, tracheal, and mediastinal nodes.
Large cell carcinoma. Have large nuclei, prominent nucleoli and some cytoplasm.
TTF1-, napsin A are markers for adenocarcinoma; P63 and P40 are markers for squamous cell carcinoma
Lung cancers are staged using the International staging system. List the salient features of each category
T: T1 (less than 3cm); T3 >7cm; T4= any tumor with invasion of mediastinum, heart, great vessels, trachea, RLN, esophagus, vertebral body, or carina
N: N0 = no mets; N1= ipsilateral hilar nodes; N2 = ipsilateral mediastinal or subcarinal nodes; N3 = metastasis to contralateral mediastinal or hilar nodes
M: M0 = no distant mets; M1 = distant mets present (M1a, separate tumor nodule in contralateral lobe, pleural nodules or malignant pleural effusion; M1b = distant mets)
In what stage of lung cancer do you start to see metastasis to the ipsilateral hilar nodes?
Stage IIA
In what stage do you see metastasis to ipsilateral mediastinum?
Stage IIIA
In what stage do you see mets to contralateral side?
Stage IIIB
In what stage do yo see distant mets?
Stage IV
The following descriptions are characteristics of what type of lung cancer:
- Strong link to smoking
- more common in men
- central (hilar) cavitating lesion
- can ectopically secrete PTH-related protein (PTHrP) –> parathyroid-like hypercalcemia and hypophsphatemia
- On histo: keratin pearls and IC bridges
- Tx: surgical resection (early), chemo and/or radiation (late)
Squamous cell carcinoma
The following describes what kind of carcinoma:
- most common lung cancer in non smokers females
- neuroendocrine in origin
- no assocation with smoking
Bronchial adenocarcinoma
The following describes what kind of carcinoma:
- Cancer of clara cells, mucins-secreting cells or type II pneumocytes.
- most cases have an assocation with smoking.
Bronchioalveolar adenocarcinoma
The following describes what kind of lung cancer?
- most common in men
- strong association with smoking
- very aggresive
- central lesion
- associated with ectopic production of ACTH or ADH, Lambert-Eaton syndrome
- on histo: stains for enolase, chromograinin, synaptophysin, Kulchitsky cells (small dark blue cells).
- Tx: chemo and/or radiaton
Small cell carcinoma
The following describes what kind of lung cancer?
- strong relationship with smoking
- poor prognosis
- peripheral or central lesion
- associated with gynocomastia and galactorrhea
- on Histo: pleomorphic giant cells that are very anaplastic
Large cell carcinoma
The following describes what kind of lung cancer?
- Hemorrhagic pleural effusion,
- psammoma bodies
- electron microscopy shows cells with large number of long, slender microvilli, and tonofilmanets
Mesothelioma
In general which two lung cancer tend to remain localized longer and have a slightly better prognosis than do the undifferentiated cancers?
Adenocarcinoma and squamous cell carcinoma. The other guys are usually pretty advanced by the time they are discovered
Activating mutation in what is associated with rose prognosis regardless of treatment?
KRAS
what common paraneoplastic hormones/hormone-like factors are seen in lung cancer?
- ADH –> hyponatremia
- ACTH –> cushings
- PTH, PTH-related peptide, PGE, cytokines –>hypercalcemia
- Calcitonin –> hypocalc
- Gonadotropins –> gynocomastia
- Serotonin and bradykiinin —> carcinoid syndrome
what is Lambert-Eaton myasthenic syndrome?
systemic manifestation of lung carcinoma, where muscle weakness is caused by autoantibodes directed to the neuronal calcium channel.
what systemic paraneoplastic manifestation are seen in lung carcinoma?
- Lambert-eaton myasthenic syndrome
- periheral neurophaty
- dermatologic abnormalities (acanthosis nigricans)
- leukomoid reaction
- hypercoagulable state (Trousseu syndrome )
- hypertrophic pulm osteoarthrophaty
- Horner syndrome ( due to Pancoast tumors)
_ are low-grade malignant epithelial tumors that may arise centrally (fingerlike or spherical polypoid mass that project into lumen of bronchus covered by intact mucosa) or peripherally (collar-button lesion, solid and nodular).. Seen in younger than 40, nonsmoker commonly
Carcinoid tumors
which form of carcinoid is more likely to grow in a disorganized fashion and invade lymphatics with dense-core granules characteristic of other neuroendocrine tumors with serotonin, neuron-specific enolase, boobesin, calcitonin and other
Atypical carcinoid
What are some salient clinical features of carcinoid tumors?
- cough, hemopytsis, impaired drainage, bronchietasis, emphysema and atelectasis
- capable of producing class carcinoid syndrome with attacks of diarrhea, flushing and cyanosis.
- Most do not metastasize thus amenable to resection
- 95% 5yr survival
Lung hamartoma, most commonly containing cartilage, is associated with chromosomal aberration involving _ or _
6p21 or 12q14-q15
_ primarily affects young women of childbearing age (probably related to estrogen), characterized by proliferation of perivascular epitheloid cells that express markers of both melanocytes and smooth muscle cells.
Lymphagioleiomyomatosis
Lymphogioleiomyomatosis is commonly associated with loss of function mutation in _
tumor suppressor TSC2 (encodes tuberin), negative regulator of mTOR, a key regulator cellular metabolism
how to lymphagioleiomyomatosis pt present clinically?
- dyspnea or spontaneous pneumothorax with emphysematous changes.
- slow growing over several decades
what gene mutation is implicated in inflammatory myofibroblastic tumor and what age group does it affect commonly?
ALK gene located on 2p23
- affects kids
- presents with fever, cough, chest pain, hemoptysis
- image shows: usually single, round, well defined, peripheral mas with calcium deposit graish white in color.
what gene mutation is implicated in inflammatory myofibroblastic tumor and what age group does it affect commonly?
ALK gene located on 2p23
- affects kids
- presents with fever, cough, chest pain, hemoptysis
- image shows: usually single, round, well defined, peripheral mas with calcium deposit grayish white in color.
A 68-year-old male is diagnosed with squamous cell carcinoma in the upper lobe of his right lung. A chest radiograph can be seen in image large coin shaped lesion at the apex of the right lung. Which of the following would you most expect to find in this patient?
- Polydipsia
- Digital clubbing
- Superior vena cava syndrome
- Anisocoria
- Lateral gaze palsy
- Anisocoria
Pt has pancoast’s tumor. A Pancoast tumor is a lung cancer located in the apex of the lung. Pancoast tumors are classically associated with ipsilateral Horner’s syndrome: ptosis (eyelid droop), miosis (pinpoint pupil), and anhydrosis (lack of sweating).
Pleural effusion are commonly either inflammatory or noninflammatory. What are common causes of inflammatory?
“pleuritis”
- TB, pneumonia, abscess, radiation, uremia.
- presents as empyema (yellow green, local, creamy push with lots of neutrophils); or hemorrhagic pleuritis
What are some common noninflammatory pleural effusions?
- hydrothorax (associated with CHF, found in base with upright)
- Chylothorax = milky fluid of lymph, fat due to lymph obstruction
- hemothorax (ruptured aorta, penetrating truma
- Pneumothorax = air (spontanous idiopathic pneumo seen in young adults that rupture a bulla into subq tissue; tension pneumo = tissue act as a valve flap allowing air into pleural space on inflation but not back out- associated with great vessel occluded leading to hypotension and mediastinal shift away from injured lung)
Metastasis from the lung common goes to _.
brain, liver, but LOVE adrenal glands. Mets to the lungs can come from anywhere
these tumors are 1-2cm mass on the pleural surface that shows whorls of reticulin and collagen fibers and are positive for CD34+ and keratin-negative by immunostatining.
Solitary fibrous tumor.
Associated with cryptic inversion of chromosome 12 involving genes NAB2 and STAB6 rearrangement creating a NAB2-STAT6 fusion gene –> chimeric transcription factor
Mesothelioma is associated with homozygous deletion of _
tumor suppressor gene CDKN2A/NK4a.
visualized using FISH to see chromosome 9p
What are the three types of mesothelioma and what are their salient features?
- Epitheloid (marker positive: keratin proteins, calretinin, Wilm’s tumor 1, cytokeratin 5/6 and D2-40)
- Sarcomatoid: resembles spindle cell sarcoma , resembling fibrosarcoma.
- Mixed type (biphasic) contains both epitheloid and sarcomatoid patterns
what are the common offenders of infectious rhinitis?
adenoviruses, echoviruses, and rhinovirus
How does infectious rhinitis usually present?
- acute
- 98% caused by virus
- initial phase: nasal mucosa is thickened, edematous, and red; nasal cavities are narrowed turbinates are enlarged.
- secondary bacterial infection can enhance the inflammatory reaction and produce mucoprulent or suppurative exudate
- nasal congestion, mucopurulent nasal discharge, pain and pressure, headache, olfactory disturbance, post nasal drainage, cough
how does allergic rhinitis present?
- IgE-mediated
- seasonal
- perennial: rxn to perennial aeroallergens including dust mites, mold, animal dander, pollen
- episodic
Nasal polyps is due to recurrent attacks of _.
rhinitis
what are nasal polyps composed of?
hyperplastic or cystic mucous glands, infiltrated with a variety of inflammatory cells, including neutrophils, eosinophils and plasma cells with occasional clusters of lymphocytes
In the absence of infection, the mucosal covering is intact, but with chronicity it may become infected and ulcerated
In chronic rhinitis, what contributes to the bacterial infection?
a deviated nasal septum or nasal polyps with impaired drainage of secretion
A 15-year-old boy presents to with clear fluid discharge from his nose for 2 days duration. This has also been associated with sneezing. On nasal exam, the mucosa and turbinates appear edematous and slightly bluish. what is the most likely diagnosis?
Allergic rhinitis
While acute sinusitis is most commonly preceded by acute or chronic rhinitis, maxillary sinusitis occasionally arises by extension of _
periapical infection through the bony floor of sinus, offending agents are usually those found in oral cavity
what are the risk factors for sinusitis?
- kartagener’s disasee
- cystic fibrosis
- wegener’s granulomatsis
- smoking
A 4-year-old boy is noted by his pediatrician to have recurrent respiratory infections. If this child was born with a genetic defect in ciliary function, which of the following could be seen as part of his presentation and work-up?
- Abnormally concentrated sweat on sweat testing
- A saddle nose deformity on physical exam
- A right-sided cardiac silhouette on chest radiograph
- A history of Hirschprung’s disease
- A history of delayed umbilical separation
- A right-sided cardiac silhouette on chest radiograph
The child in this vignette most likely has Kartagener’s syndrome, characterized by a hereditary defect in ciliary function. This condition also presents with dextrocardia (a heart on the right side).
_ is infection of paranasal sinus due to undrained collection of pus
sinusitis. Maxilary sinuses are commonly involved.
- can be bacterial or fungal
Acute sinusitis is sinusitis with a sudden onset that lasts less than a month and most commonly caused by what _
- s. pneumoniae
- H. influenzae
- Moraxella cattarhalis
necrotizing ulcerating lesion of the nose and URT may be produced by _
- acute fungal infection such as mucormycosis (esp in diabetics and immunocmpromised). pts will present with sudden onset of nose bleed, ulcerated nasal mucosa, proptosis and periorbital edema
- Granulomatosis with polyangiitis
- Extranodal NK/T cell lymphoma, nasal type in which tumor cells harbar EBV
what are the common causative agents of pharyngitis and tonsilitis?
viral upper respiratory infections commonly imlicated are rhinoviruses, echoviruses, adenoviruses and less commonly RSV.
Bacterial infection may be superimposed on these viral infection or can be primary. Most common are beta hemolytic strep but s. aureus is also implicated
_ is a benign,highly vascular tumor that occurs almost exclusively in adolescent males who are often fair-skinned and red headed. Has an association with familial adenomatous polyps. Treated with surgery but can recur
nasopharyngeal angiofibroma
_ is a benign neoplasm seen in males 30-60, arising from respiratory or schneiderian mucosa lining the nasal cavity and paranasal sinuses and comes in three flavors: exophytic (most common), endophytic, and cylindrical.
Sinunasal (Schneiderian papilloma.
What virus has been implicated in exophytic and endophytic sinonasal papilloma?
HPV types 6 and 11
which form of sinonasal papilloma is locally aggressive with papillomatous proliferation of squamous epithelium that invaginates underlying storma. Has high rates of recurrence if not adequately excised and can have serious complications such as invasion of orbit or cranial vault. 10% can undergo malignant transformation
Exophytic
Olfactory neuroblastoma arises from where?
neuroectodermal olfactory cells within the mucosa, particularly superior aspect of nasal cavity.
These are the same small, blue, round cells seen in many other neoplasms such as lymphoma, small cell carcinoma, and etc.
what markers can be used to test for olfactory neuroblastoma?
Because it’s neuroendocrine in origin, you can use enolase, synaptophysin, CD56, and chromogranin
Often mistaken for squamous cell carcinoma, this carcinoma can occur in nasopharynx, salivary gland, or midline structures in thorax or abd. It is extremely aggressive and resistant to conventional therapy–most survive less than a yr.
NUT midline carcinoma
What genetic abnormality gives rise to NUT midline carcinoma?
translocation that create fusion genes encoding chimeric proteins coprised of most of NUT, a chromatin regulator and a protein of a chromatin reader protein usually BRD4.
Keratinizing squamous cell carcinoma, nonkeratinzing squamous cell carcinoma and undifferentiated/basoloid carcinomas are the three patterns of what carcinoma?
nasopharyngeal carcinoma
what three factors influence the origin of nasopharyngeal carcinoma?
- heredity
- age
- infection with EBV
Common in pats of Africa as most frequent childhood cancer. Also seen Chinese adults.
which form of nasopharyngeal carcinoma has the best progonosis and the worst prognosis
Best: nonkeratizing type
Worse: keratinizing type
causes of laryngitis
- alleric,
- viral
- bacterial
- chemical insults
- smoking
- GERD
- systemic infections such as TB and diphtheria
what is croup?
laryngotracheobronchitis in kids in which inflammatory narrowing of the airway produces the inspiratory stridor so frightening to parents. Most common cause is parainfluenza virus
what is vocal cord nodule caused by?
excessive cause, usually bilateral.
- composed of degenerative (myxoid) connective tissue
- pt presents with hoarseness, resolves with rest
_ are benign neoplasms, usually located on true vocal cords, that form soft, respberry like prolifeation rarely more than 1cm in diameter. On histo multiple slender, finger like projection supported by central fibrovascular cores covered by stratified squamous epithelium. Ulceration can occur accompanied by hemoptysis
Squamous papilloma and papillomatosis
How does juvenile laryngeal papillomatosis differ from adult form?
papillomas are usually single in adults but are often multiple in kids.
what is the common causative agent of squamous papilloma and papillomatosis?
HPV 6 and 11.
Don’t usually become malignant but do recur
what sequence of alterations are seen in the larynx related to carcinoma of larynx?
- hyperplasia, atypical hyperplasia, and dysplasia
- carcinoma in situ
- carcinoma
what are the risk factors of carcinoma of the larynx?
- smoking
- alcohol
- nutritional factors
- asbestos
- irradiation
- infection with HPV
what do the laryngeal carcinoma arise from? how do they look?
squamous epithelial lining of vocal cord.
- typically in men in 50s, smoker
- dysplastic sq epithelium, fungating bulky, mass protruding from laryngeal surface often w/ ulceration
a 25-year-old male, shot in the right lower chest and has been stable for the past two hours. He has been getting progressively more short of breath. Vitals reveal temperature 37 degrees Celsius, heart rate of 121, blood pressure of 100/70, respiratory rate 23, and oxygen saturation of 89% on room air. You hear diminished breath sounds on the right side. His oxygen saturation is dropping. A bedside x-ray is taken and reveals the following pneumothorax with trachea deviated away from the pneumothorax. What is the next step in management?
- Insert a chest tube
- Place the patient on oxygen and insert a chest tube
- Perform a needle thoracostomy
- Obtain an arterial blood gas
- Perform a thoracotomy
- Perform a needle thoracostomy
Pt has tension pneumothorax due to the trauma.
An AIDS pts presents with symptoms of pneumonia. Cryptosporidium parvum are found in stool specimen. Bronchoalveolar lavage is performed and shows pink, foamy exudate with little inflammation. which additional findings on microscopic exam is most likely to have in BAL specimen?
Multiple cysts with GMS stain.
Pneumocystis jiroveci pneumonia is associated with AIDS. PCP infection produces an exudate composed of pneumocystis cysts and trophozoites with little accompanying inflammation.
