Respiratory Pathology (Pathoma) Flashcards
Rhinitis
Inflammation of the nasal mucosa; rhinovirus is mcc
Presents w/ sneezing, congestion, and runny nose (aka common cold)
Nasal Polyp
Protrusion of edematous inflamed nasal mucosa
Usually secondary to repeated bouts w/ rhinitis (adults only!)
Also associated w/ cystic fibrosis (must work up kids w/ polyps w/ sweat test!)
Can be associated w/ aspirin induced asthma
Allergic Rhinitis
Subtype of rhinitis due to Type I HS reaction (i.e. pollen)
Characterized by inflammatory infiltrate w/ eosinophils
Associated w/ asthma and eczema
Aspirin-intolerant asthma
Triad of asthma, aspirin (other NSAIDs too!) induced bronchospasms, and nasal polyps
Stem roots often say “woman w/ chronic pain presents w/ intermittent asthma –> makes you assume NSAID use and doesn’t give you asthma)
Angiofibroma
Benign tumor of nasal mucosa composed of large blood vessels and fibrous tissue
Classically seen in adolescent males
Presents w. profuse epistaxis
Nasopharyngeal carcinoma
Malignant tumor of the nasopharyngeal epithelium
Associated w/ EBV
Classically seen in African children and Chinese adults
Biopsy usually reveals pleomorphic KERATIN POSITIVE epithelial cells (poorly differentiated scc) in a background of lymphocytes
Often presents w/ involvement of cervical lymph nodes.
Acute Epiglottitis
Inflammation of the epiglottis caused by Hib (also Strep pyo) , especially in nonimmunized (but can occur in immunized)
Presents w/ rapid onset; high fever, sore throat, drooling w/ dysphagia, muffled voice, and inspiratory stridor
Risk of airway obstruction
Thumbrint sign on lateral X ray
Laryngotrachealbronchitis (croup)
Inflammation of upper airway
Parainfluenza virus is mcc
Presents w/ hoarse BARKING cough and inspiratory stridor
Steeple sign on x ray
Vocal Cord Nodule (Singer’s Nodule)
Nodule that arises on true vocal cord
Due to excessive use (think pitch perfect); usually bilateral
Composed of degenerative myxoid connective tissue
Presents w/ hoarseness and resolves w/ resting of voice
Laryngeal Papilloma
Benign papillary tumor of the vocal cord
Due to HPV 6 and 11; papillomas are usually single in adults and multiple in children
Presents w/ hoarseness
Laryngeal Carcinoma
Squamous cell carcinoma usually arising from the epithelial lining of the vocal cord
Risk factors are alcohol and tobacco; rarely can arise from laryngeal papilloma
Presents w/ hoarseness, cough, and stridor
Pneumonia
Infection of the lung parenchyma
Occurs when normal defenses are impaired (cough, damage to mucocilliary escalator, or mucus plugging)
Clinical features include fever, chills, productive cough w/ yellow-green (pus) or rusty (bloody) sputum, tachypnea w/ pleuritic chest pain,
Physical exam: decreased breath sounds, dullness to percussion, whisper pectoriloquy, egophony (e–>a) and elevated WBC count.
Dx made by CXR (gold standard), sputum gram stain and culture, and blood cultures.
Three patterns on CXR: lobar pneumonia, bronchopnumonia, and interstitial pnuemonia.
Lobar pneumonia
Characterized by consilidation of an enitre lobe of lung (effectively a shunt)
Usually bacterial; MCC are Strep pneumoniae (95%) and Klebsiella pneumoniae
Classic gross phases:
- ) Congestion - due to congested vessels and edema
- ) Red hepatization - due to exudate, neutrophils, and hemorrhage filling the alveolar air spaces. Causes lung to go from spongy (normal) –> solid (liver like).
- ) Gray hepatization - due to degradation of red cells w/ in exudate
- ) Resolution –> type II pneumocyte is the stem cell of the lung repairing damaged dissue (they also make surfactant)
Bronchopneumonia
Characterized by scattered patchy consolidation centered around bronchioles; often multifocal and bilateral
Characterized by variety of bacterial organisms
Aspiration pneumonia
Seen in patients at risk for aspirations (alcoholica, comatose patients, elderly, etc.)
Most often due to ANaerobic bacteria in oropharynx (i.e. bacteriodes, fusobacterium, and peptococcus)
Classically seen in a RLL absess (right main stem broncus branches at a more verticle angle than the left and is wider.)
Interstitial pneumonia
Characterized by diffuse in interstitial infiltrates
Presents w/ relatively mild upper respiratory sx (aka walking pneumonia) minimal sputum and low fever
“atypical presentation and atypical bugs”
Caused by bacteria and viruses
MCC: mycoplama pneumoniae (#1), chylamydia pneumoniae, RSV, cytomegaolvirus, influenza virus, and coxiella burnetti
Strep pneumoniae
MCC of community acquired pneumonia and secondary pneumonia (bacterial pneumonia superimposed on a viral URI)
Usually seen in middle-aged adults and elderly
Klebsiella pneumoniae
2nd MCC of lobar pneumonia
Enteric flora that is aspirated; affects malnourished and debilitated individuals, especially elderly in nursing home, alcoholics, and diabetics.
Thick mucoid capsule results in gelatinous (currant jelly) sputum
Often complicated by abcess
Staph Aureus
2nd MCC of secondary pneumonia; often complicated by abscess or empyema
Often invades after flu.
Bronchopneumonia
Haemophilus influenza
Common cause of secondary pneumonia and pneumonia superimposed on COPD (leads to exacerbation of COPD)
Bronchonpneumonia
Pseudomonas aeruginosa
Water lover!
Bronchopnuemonia in CF patients and intubated patients
Moraxella catarrhalis
Community acquired bronchopnuemonia and pneumonia superimposed on COPD (leads to exacerbation of COPD)
Legionella pneumophilia
Discovered at American Legion conference from air conditioner in hotel.
Community acquired bronchopneumonia, pneumonia superimposed on COPD, or pneumonia in immunocompromised states
Transmitted from water source (cooling towers, grocery store mist, etc.)
Intracellular organism that is best visualized on silver stain.
Also can cause tubulointerstitial nephritis –> hyponatremia (per Golgan)
Mycoplama pneumoniae
MCC atypical pneumonia
Usually affects young adults (i.e. military recruits or college students in dorms)
Complications include cold autoimmune hemolytic anemia (IgM) and erythema muttiforme. Not visivle on gram stain due to lack of cell wall!
Chlamydia pneumoniae
Second MCC of atypical pneumonia
Young adults
RSV
MCC of atypical pneumonia in infants (older than 6 weeks)
Also key cause of bronchiolitis
CMV
Atypical pneumonia w/ posttransplant / late stage AIDS
Influenza virus
Atypical pneumonia in the elderly, immunocompromised, and those w/ preexisitng lung disease.
Also increases risk for superimposed S. aureus or H. flu pneumonia
Coxiella burnetti
Atypical pneumonia w/ high fever (Q fever); seen in farmers and vets (Coxiella spores are deposited on cattle by ticks or are present in cattle placentas).
Is a rickettsial organism, but it is distinct from most other ricketssiae because it”
- ) causes pneumonia,
- ) doesn’t require arthropod vector for transmission (survives as highly heat-resistant endospores)
- ) does not form a skin rash
Tuberculosis
Infx due to inhalation of Mycobacterium tuberculosis
Primary TB arises w/ initial exposure:
- )Results in focal, caseating necrosis in lower lobe (subpleural upper part of lower lobe or lower part of upper lobe) and hilar lymph nodes that undergoes fibrosis and calcification forming Ghon complex.
- ) Usually asymptomatic, but positive ppd
Secondary TB –> reactivation of M. tb:
- )Reactivation is commonly due to AIDS; may also be seen w/ aging
- ) Occurs at apex of lung (high 02 and M. tb is aerobe!)
- ) Forms cavitary foci of caseous necrosis; may also lead to miliary pulmonary TB or tuberculous bronchopneumonia
- ) Clinical features include fevers, night sweats, cough w/ hemoptysis, and weight loss
- ) Biopsy reveals caseating granulomas; AFB stain (Wright-Giemsa)
- ) Systemic spread often occurs and can involve any tissue commonly: meninges (esp. base of brain –> meningitis), cervical lymph nodes, kidneys (sterile pyuria), and lumbar vertebrae (Pott’s disease)
COPD
Group of diseases characterized by airway obstruction; lung does not empty –> air trapping
- ) Volume of air that can be forcefully expired decreases (decreased FVC), espeiclally during first second (FEV1). –> FEV1/FVC ratio decreasing is hallmark
- ) TLC is usually increased (air trapping!)
4 main diseases: Chronic Bronchitis, Emphysema, Asthma, and Bronchiectasis
Chronic Bronchitis
Chronic productive cough lasting at least 3 months over a minimum of 2 years; highly associated w/ smoking
Characterized by hypertrophy of bronchial mucinous glands –> leads to increased thickness of mucus glands relative to bronchial wall thickness (Reid index increases to >50%; normal is mucus plugs trap carbon dioxide; increased PaCO2 and decreases PaO2
3.) Increased risk of infection and cor pulmonale
Emphysema
Destruction of alveolar sacs (balloon –> grocery bag) –> loss of elastic recoil and collapse of airways during exhalation results in obstruction and air trapping
Due to imbalance of proteases and antiproteases:
- )Inflammation in the lung normally leads to release of proteases by neutrophils and macrophages
- ) Alpha-1 antitrypsin (A1AT) neutralizes proteases
- ) Excessive inflammation (smoking) or lack of A1AT leads to destruction of the alveolar air sacks
Smoking is mcc of emphysema:
- ) pollutants in smoke lead to excessive inflamation and protease-mediated damage
- ) Results in centracinar emphysma (first thing air hits!) that is most severe in upper lobes (smoke rises!)
A1AT deficiency is a rare casue of emphysema:
- ) lack of antiprotease leaves the air sacs vulnerable to protease-mediated damage.
- ) results in panacinar emphysema that is most severe in lower lobes
- ) liver cirrhosis may also be present
- A1AT deficiency is due to misfolding of the mutated protein
- Mutatnt A1AT accumulates in the ER of hepatocytes –> liver damage
- Biopsy reveals pink, PAS-positive globules in hepatocyte - )Disease severity is based on degree of A1AT deficiency
- PiM is the normal allele; two copies are normally expressed (PiMM)
- PiZ is the most common clinically relevant mutation; results in significantly lower levels of A1AT
- PiMZ heterozygote are usually asymptomatic –> increased risk –> very susceptible if smoking
- PiZZ - homozygotes are at significant risk for emphysema and cirrhosis
Clinical features:
- ) Dyspnea and cough w/ minimal sputum
- ) Prolonged expiration w/ pursed lips (“pink-puffer”_
- ) weight loss –> due to increased breathing work
- ) Increased A-P diameter of chest (barrel chest)
- ) Hypoxemia and cor pulmonale are late complicaitons
Alpha-1 Antitrypsin Deficiency
Disease severity is based on degree of A1AT deficiency
- PiM is the normal allele; two copies are normally expressed (PiMM)
- PiZ is the most common clinically relevant mutation; results in significantly lower levels of A1AT
- PiMZ heterozygote are usually asymptomatic –> increased risk –> very susceptible if smoking
- PiZZ - homozygotes are at significant risk for emphysema and cirrhosis
Asthma
REVERSIBLE airway bronchoconstriction, most often due to allergic stimuli (atopic asthma)
Presents in childhood; often associated w/:
- allergic rhinitis
- eczema
- family hx of atopy
Pathogenesis = Type I HS
- ) Allergens induce TH2 CD4s of genetically susceptible individuals
- )TH2s secrete IL-4 (mediates class switch to IgE), IL-5 (attracts eosinophils), and IL-10 (stimulates TH2s and inhibits TH1s)
- ) Reexposure to allergen leads to IgE activation of mast cells
- release of preformed histamine granules and generation of LTC,D,E4. Leads to bronchoconstriction, inflammation, and edema (early phase rxn)
- Inflammation, especially major basic protein, derived from eosinophils, damages cells and perpetuates bronchoconstriction (late phase rxn)
Clinical features are epidsodic and related to allergen exposure
- ) Dyspnea and wheezing
- ) Productive cough, classically w/ spiral shaped mucus plugs (Curshman Spirals) and eosinophil-derived crystals (Charcot-Leyden crystals)
- ) Severe, unrelenting attack can result in status asthmaticus and death
May also arise from nonallergenic causes (non-atopic asthma) such as exercise, viral infection, aspirin (triad w/ nasal polyps), and occupational exposures
Some may present w/ cough variant astma
Dx w/ methacoline challenge
Rx: Beta agonists, Steroids, Leukotriene inhibitors, Chromolyn, etc.
Bronchiectasis
Permanent dilitation of bronchioles and bronchi –> loss of airway tone results in air trapping
Due to necrotizing inflammation w/ damage to airway walls.
Causes:
- Cystic Fibrosis (MCC in US)
- TB (MCC globally)
- Kartagener’s syndrome (rare, but often tested)
- Tumor or foreign body
- Necrotizing infx
- Allergic bronchopulmonary aspergillosis
Clinical features:
- ) Cough, dyspnea, and foul smelling sputum
- ) Complications include hypoxemia w/ cor pulmonale and seconary (AA) amyloidosis
Kartagener’s syndrome
Inherited defect of the dynein arm which is necessary for cilia movement.
Results w/ sinusitis, infertility (sperm and transport of fertilized egg), and situs inversus.
Allergic Bronchopulmonary Aspergillosis
HS reaction to Aspergilus leads to chronic inflammatory damage.
Usually seen in pts. w/ CF or asthma
Restricitve Diseases
Basic principles:
- ) Characterized by restricted filling of the lungs (decreased TLC, FEV1 and FVC; FEV1/FVC ratio is increased)
- ) Most commonly due to interstitial diseases of the lung; may also arise w/ chest wall abnormalities (massive obesity)
Like going from a balloon –> water balloon vs. Obstructive is like going from balloon –> grocery bag
Idiopathic Pulmonary Fibrosis
Fibrosis of the lung interstitium
Etiology is unknown. likely related to cyclical lung injury; TGF-B from injured pneumocytes induces fibrosis
Secondary causes of IF such as drugs (bleomycin and amiodarone) and radiation therapy must be excluded
Clinical features:
- ) Progressive dyspnea and cough
- ) Fibrosis of lung on CT; initially seen in subleural patches, but eventually diffuse fibrosis w/ end stage honeycomb lung
- ) Rx = lung transplant
Pneumoconiosis
Interstitial fibrosis due to occupational exposure; requires chronic exposure to small particles that are fibrogenic (coal dust, silica, berylliosis, and Asbestososis)
Alveolar macrophages engulf foreign particles and induce fibrosis.
Coal Workers’ Pneumoconiosis
Exposure - Carbon dust; seen in coal miners
Pathologic findings - massive exposure leads to diffuse fibrosis (black lung); associated w/ RA (Caplan Syndrome)
Mild exposure to carbon (i.e. pollution) results in anthracosis. This is a collection of carbon-laden macrophages –> not clinically significant.
Caplan Syndrome
Pneumoconiosis and connective tissue disease (i.e. coal worker’s plus RA)
Silicosis
Silica exposure seen in sandblasters and silica miners
Fibrotic nodules in upper lobes of the lung
Increased risk for TB; silica impairs phagolysosome formation by mphages
Berylliosis
Beryllium seen in beryllium miners and workers in the aerospace industry
Noncaseating granulomas in the lung, hilar lymph nodes, and systemic organs. (must ddx vs sarcoid!)
Increased risk for lung cancer.
Asbestosis
Asbestos fibers; seen in construction workers, plumbers, and shipyard workers.
Fibrosis of lung and pleura (plaques) w/ increased risk of lung carcinoma (more common) and mesothelioma
Lesions may contain long, golden-brown fibers w/ associated iron asbestos bodies (confirm exposure).
Look like dumbells –> and are ironQ
Sarcoidosis
Systemic disease characterized by noncaseating granulomas in multiple organs classically seen in AA females
Etiology is unknown; likely due to CD4 T cell response
Granulomas most commonly involve the hilar lymph nodes and lung leading to restrictive lung disease –> characteristic stellate inclusions (asteroid bodies) are often seen within giant cells of granulomas
Other commonly involved tissues include: uveitis, cutaneous nodules or erythema nodosum, and salivary and lacrimal glands (mimics Sjogren’s). Almost any tissue can be involved.
Clinical features:
- )Dyspnea or cough (most common presenting sx)
- ) Elevated serum ACE
- ) Hypercalcemia (1-alpha hydroxylase activity of epitheliod histiocytes activates vitamin D)
- ) Rx is steroid –> often spontaneously resolves
Hypersensitivity Pneumonitis
Granulomatous reaction to inhaled organic antigens (i.e. pigeon breeder’s lung)
Presents w/ fever, cough, and dyspnea hours after exposure; resolves w/ removal of the exposure
Chronic exposure leads to interstitial fibrosis
Pulmonary HTN
High pressure in the pulmonary circuit (MAP > 25 mm Hg)
Characterized by atherosclerosis of the pulmonary trunk, smooth muscle hypertrophy of the pulmonary arteries, and intimal fibrosis; plexiform lesions are seen w/ severe, long standing disease
Leads to RV hypertrophy and eventual cor pulmonale
Presents w/ exertional dyspnea or right sided CHF
Can be primary or secondary
Primary Pulmonary Hypertension
Classically seen in young adult females
Etiology is unknown; some familial forms are related to inactivating mutations of BMPR2 leading to proliferation of vascular smooth muscle
Seocndary Pulmonary HTN
Due to hypoxemia (i.e. COPD, interstitial lung disease, or sleep apnea) or increased volume in the pulmonary circuit (congenital heart disease. May also arise w/ recurrent PE.
Acute Respiratory Distress Syndrome
Diffuse damage to the alveolar-capillary interface (diffuse alveolar damage)
Leakage of protein-rich fluid leads to edema that combines w/ necrotic eptihelial cells to form hyaline membranes in alveoli
Clinical features:
- ) Hypoxemia and cyanosis w/ respiratory distress - due to thickened diffusion barrier and collapse of air sacs (increased surface tension)
- ) White out on CXR
Secondary to a variety of disease processes including sepsis, infection, shock, trauma, aspiration, pancreatitis, DIC, hypersensitivity rxns, nad drugs. –> activation of neutrophils induces protease and free radical mediated damage of type I and II pneumocytes
Rx:
- ) Treat underlying cause
- ) Ventilation w/ Positive End Expiratory Pressure (PEEP)
Recovery may be complicated by interstitial fibrosis; damage and loss of type II pneumocytes leads to scarring and fibrosis.
Neonatal Respiratory Distress Syndrome
Respiratory distress due to inadequate surfactant levels
- ) Surfactant is made by our type II pneumocytes; phophatidyl choline (lecithin) is the major component
- ) Surfactant decreases surfact tension in the lung, preventing collapse of alveolar air sacs after expiration
- ) Lack of surfactant leads to collapse of airsacs and formation of hyaline membranes
Associated w/;
- ) Prematurity - surfactant production begins at 28 weeks; adequate levels not reached until around 34 weeks
- Amniotic fluid lecithin to sphingomyelin ratio is used to screen for lung maturity (
Lung Cancer Principles
MCC of cancer mortality in the US. Average age of presentation is 60.
Key risk factors: cigarette smoke, radon, and asbestos
- )Cigarette smoke contains over 60 carcinogens; 85% of lung cancers occur in smokers
- Polycyclic aromatic hydrocarbons and aresenic are particularly mutagenic
- Cancer risk is directly related to the duration and amount of smoking (pack years) - ) Radon is formed by radioactive decay of uranium, which is present in soil
- Accumulates in closed spaces such as basements
- Responsible for most of the public exposure to ionizing radiation; 2nd most frequent cause of lung carcinoma in the U.S.
Presenting sx are nonspecific (i.e. cough, weight loss, hemoptysis, and postobstructive pneumonia)
Imaging often reveals a solitary nodule (coin lesion); biopsy is necessary for dx of cancer.
- )Benign lesions, which often occur in younger patients, can also produce a coin lesion
- Granuloma –> TB or fungus (Histo in Midwest)
- Bronchial hamartoma - benign tumor of lung tissue and cartilage. Often calcified (calcified = good sign)
Lung Carcinoma is divided into 2 categories:
- ) Small Cell (15%) - usually not amenable to surgery
- ) Non-small cell (85%) - treated w/ surgical resection
Overall 15% 5 year survival; often presents late due to the absence of an effective screening method.
TNM staging
T - Tumor size and local extension
- pleural invovlement is classically seen w/ adenocarcinoma
- Obstruction of the SVC leads to distended neck veins w/ edema and blue discoloration of arms and face (SVC syndrome)
- Involvement of recurrent laryngeal nerve (hoarsness) or phrenic nerve (diaphragmatic paralysis)
- Compression of sympathetic chain leads to Horners (PAM); usually due to a pancoast tumor
N- Spread to regional lymph nodes (Hilar and mediastinal)
M - Metastasis do distant site. Unique is adrenals. Common are bone, brain, and liver.
Small Cell Carcinoma
Histology - poorly differentiated small cells; arises from neuroendocrine (Kulchitsky ) cells
Association: Male smokers
Location: Central
Rapid growth and early metastasis; may produce ADH (SIADH) or ACTH (Cushings) or cause Lambert-Eaton syndromes
Rx: “too small to resect” chemo and radiation only!
Squamous cell carcinoma
Histology - Keratin pearls or intracellular bridges
Association - most common tumor in male smokers
Location: central
May produce PTHrP (causing hypercalcemia)
Adenocarcinoma
Histology: Glands or mucin
Association: Most common tumor in nonsmokers and female smokers (Rick’s daughter!)
Location: peripheral
Large Cell Carcinoma
Histology: Poorly differentiated large cells (no keratin pearls, intracellular bridges, glands, or mucin)
Association: Smoking
Central or peripheral
Poor prognosis
Bronchioalveolar carcinoma
Histology: Columnar cells that grow along preexisting bronchioles and alveoli; arises from Clara cells
Not related to smoking
Peripheral
May present w/ pneumonia like consolidation on imaging. Excellent prognosis
Carcinoid tumor
Histology: Well differentiated neuroendocrine cells; chromogranin positive.
Not related to smoking
Central or peripheral: when central, classsically forms a polyp-like mass in the bronchus.
Low grade malignancy, rarely can cause carcinoid syndrome (flushing, diarrhea, facial lesions, tachycardia)
Metastasis to the lung
Most common sources are breast and colon (also kidney, bladder, and prostate)
Multiple canon-ball nodules on histology
More common than primary tumors.
Spontaneous PTX
Accumulation of air in the pleural space due to the rupture of an emphysematous bleb; seen in young adults –> results in collapse of a portion of the lung; trachea shifts towards the collapse.
Tesion PTX
Accumulation of air in the pleural space arising w/ a penetrating chest wall injury –> air enters the pleural space, but can’t exit; trachea is pushed to the opposite side.
Medical emergency –> chest tube.
Mesothelioma
Malignant neoplasm of mesothelial cells; highly associated w/ occupational exposure to asbestos.
Presents w/ recurrent pleural effusions, dyspnea, and chest pain. Tumor encases the lung.
