Respiratory - Pathology Flashcards
Rhinitis: Mechanism and Presentation
Inflammation of nasal mucosa
Sneezing, congestion, runny nose
What is the most common cause of rhinitis?
Adenovirus
Allergic Rhinitis: Mechanism. What type of hypersensitivity?
Type I hypersensitivity (e.g. to pollen) Subtype of rhinitis
Allergic Rhinitis: Histology
Inflammatory infiltrate with eosinophils
What is allergic rhinitis associated with?
Asthma and eczema
Nasal polyp: Mechanism and Causes
Protrussion of edematous, inflamed nasal mucosa
Repeated rhinitis, cystic fibrosis and aspirin-intolerant asthma
What is the triad of aspirin-intolerant asthma?
Asthma, Aspirin-induced bronchospasm, nasal polyps
Seen in 10% of asthmatic adults
What is a nasopharynx angiofibroma?
benign tumor of nasal mucosa of large blood vessels and fibrous tissues, classically seen in adolescent males Present with profuse epistaxis
Nasopharyngeal carcinoma
malignant tumor of nasopharyngeal epithelium often involves cervical lymph nodes
What is nasopharyngeal carcinoma associated with? Which population?
EBV African children and Chinese adults
Nasopharyngeal carcinoma: biopsy
pleomorphic keratin-positive epithelial cells (poorly differentiated SCC) in background of lymphocytes
Acute epiglottis: Presentation
Inflammation of epiglottis
Fever, sore throat, drooling with dysphagia, muffled voice, inspiratory stridor, risk of airway obstruction
What is the most common cause of acute epiglottis?
H. flu type b Especially in nonimmunized children
Laryngotracheobronchitis (Croup)
Inflammation of upper airway
Presents with hoarse, “barking” cough and inspiratory stridor
What is the most common cause of laryngotracheobronchitis?
Parainfluenza virus
What is a singer’s nodule?
Vocal cord nodule - arise on true vocal cord
Presents with hoarseness; resolves with resting of voice
What is the cause of a vocal cord nodule?
Excessive use of vocal cord, usually bilateral
Vocal cord nodule: histology
degenerative (myxoid) connective tissue
Laryngeal papilloma
Benign papillary tumor of vocal cord Presents with hoarseness
What is the common cause of laryngeal papilloma?
HPV 6 and 11
How are laryngeal papillomas presented in children vs adults?
Children - multiple Adults - single
Laryngeal carcinoma
Squamous cell carcinoma usually from epithelial lining of vocal cord
Presents with hoarseness, other sings include cough and stridor
Risk factors for laryngeal carcinoma
alcohol and tobacco
Rarely arise from laryngeal papilloma
What is choanal atresia?
Unilateral or bilateral bony septum between nose and pharynx
Newborn cannot breath through nose; cyanosis when breast-feeding and pink up after crying
What is the most common polyp in adults?
Allergic polyp
What test to order when a child has nasal polyps?
Sweat test to rule out cystic fibrosis
Obstructive sleep apnea: laboratory findings
Respiratory acidosis and hypoxemia
Obstructive sleep apnea: complications
Risk for developing cor pulmonale
Diagnosis for Obstructive Sleep Apnea
Polysomnography: confirmatory test that documents period of apnea during sleep
What is the most common sinus infection in adults?
maxillary sinusitis
What is the most common sinus infection in children?
What is the most common cause of sinusitis?
viral
What is the most common bacterial pathogen causing sinusitis?
Streptococcus pneumoniae
What is the most sensitive test for sinusitis?
CT
What is pneumonia?
Infection of lung parenchyma
Occurs when normal defences are impaired (cough reflex, damage to mucociliary escalator, mucus plugging)
Presentation of Pneumonia
Fever and chills, productive cough with yellow green (pus) or rusty (bloody) sputum
Tachypnea with pleuritic chest pain, elevated WBC count
How is pneumonia diagnosed?
chest x-ray
sputum gram stain and culture
blood culture
What are the three patterns classically seen on chest x-ray for pneumonia?
lobar pneumonia
bronchopneumonia
interstitial pneumonia
What is lobar pneumonia?
Consolidation of entire lobe on lung
Causes of lobar pneumonia
Usually bacterial
Most common: strep pneumo (95%) and klebsiella pneumoniae
What is the classic gross phases of lobar pneumonia?
- congestion (congested vessels and edema)
- Red hepatization (exudates, neutrophils, hemorrhage filling alveolar air space, giving normally spongy lung a solid consistency)
- Gray hepatization (degradation of red cells within exudate)
- Resolution
What is bronchopneumonia? What is it caused by?
Scattered patchy consolidation centered around bronchioles; often multifocal and bilateral
Caused by a variety of bacterial organisms
What is interstitial (atypical) pneumonia?
Diffuse interstitial infiltrates
Relatively mild upper respiratory symptoms (minimal sputum and low fever)
What is aspiration pneumonia?
Seen in patients at risk for aspiration (alcoholics and comatose)
What are the most common causes (5) of bronchopneumonia?
S. aureus
H. flu
Pseudomonas aeruginosa
Moraxella catarrhalis
Legionella pneumophila
What are the most common causes (6) of atypical pneumonia?
Mycoplasma pneumoniae (most common)
Chlamydia pneumoniae
RSV
CMV
Influenza
Coxiella burnetii
What usually results from an aspirated pneumonia?
Right lower lobe abscess - right main stem bronchus at less acute angle than left
What are the two water loving bacterias
Pseudomonas aeruginosa
Legionella pneumophila
What is a Ghon complex?
Focal, caseating necrosis in lower lobe of lung and hilar lymph nodes that undergoes fibrosis and calcification
What is form in secondary TB?
cavitary foci of caseous necrosis; may lead to miliary pulmonary TB or tuberculosis bronchopneumonia
Wht are common sites of TB systemic spread?
Meninges (meningitis)
Cervical lymph nodes
Kidneys (sterile pyruia)
lumbar vertebrae (pott disease)
What is the virulence factor of TB?
Cord factor
What is the most common extrapulmonary site of TB?
Kidneys
What is the most common TB in AIDS?
Mycobacterium avium - intracellulare (MAC) Complex
CD4 Th cells fall below 50 cells/mm3
What is the most common cause of lung abscess?
Aspiration of oropharyngeal material
What does chest x-ray shows for lung abscesses?
cavitation and fluid level
Define COPD
Group of disease characterized by airway obstruction
Lung does not empty; air is trapped
COPD: Typical lung volume changes (FVC, FEV, FEV1/FVC ratio, TLC)
Decreased FVC
Decreased FEV1 (more than FVC)
Decreased FEV1/FVC ratio
Increased TLC (due to air trapping)
What are the 4 COPDs?
Chronic bronchitis
Emphysema
Asthma
Bronchietasis
Chronic Bronchitis
Productive cough lasting at least 3 months over minimum of 2 years
Highly associated with smoking
Chronic bronchitis: histology
Hypertrophy of bronchial mucinous glands
Increased thickness of mucus glands relative to overall bronchial wall thickness (Reid index increases > 50% - normaly is 40%)
Chronic bronchitis: Presentation
Productive cough due to excessive mucus production
Cyanosis (blue boaters) - mucus plugs trap CO2; increased PaCO2 and decreased PaO2
Increased risk of infection and cor pulmonale
What is the most common cause of bronchiectasis?
Smoking
Emphysema
Destruction of alveolar air sac from loss of elastic recoil and collapse of airways during exhalation
Describe how inbalance of proteases/antiproteases contribute to emphysema
Inflammation leads to release of proteases by neutrophils and macrophages
alpha1-antitrypsin neutrlizes proteases
excessive inflammation or lack of antitrypsin leads to destruction of alveolar air sacs
What is the most common cause of emphysema?
Smoking (pollutants in smoke lead to excessive inflammation and protease-mediated damage)
Where is smoking-associated emphysema located?
Centriacinar emphysema in upper lobes
What is A1AT deficiency?
Alpha-1 antitrypsin deficiency - rare cause of emphysema
Lack of antiprotease leaves air sacs vulnerable to protease-mediated damage
Where is A1AT-associated emphysema?
panacinar emphysema in lower lobes
What other organ besides the lungs can A1AT deficiency affect? Why?
Liver cirrhosis
misfolding of mutated protein - accumulates in ER of hepatocytes leading to damage
pink, PAS-positive globules in hepatocytes
How is A1AT inherited?
PiM is normal allele; two copies are expressed
PiZ is common clinically relevant mutation - significantly lowers circulating A1AT
What is the genotype of individual with heterozygous and homozygous A1AT deficiency? Do they have the same risk for developing disease?
Heterozygote: PiMZ: usually asymptomatic but significantly increased risk with smoking
Homozygote: PiZZ significant risk for panacinar emphysema and liver cirrhosis
Emphysema: Presentation
dyspnea and cough with minimal sputum
prolonged expiration with pursed lips (pink-puffer)
weight loss
increased AP diameter (barrel-chested)
hypoxemia and cor pulmonale as late complications
What poses a risk for spontaneous pneumothorax?
paraseptal emphysema (subpleural location)
Asthma
Reversible airway bronchoconstriction, most often due to allergic stimuli (Type I hypersensitivity)
Describe pathogenesis of asthma
Allergens induce Th2 phenotype in CD4+ Th2 cells secrete IL-4 (IgE class switch), IL-5 (attract eosinophils), IL-10 (stimulate Th2 and inhibits Th1)
Rexposure leads to IgE mediated activation of mast cells
Describe the early-phase reaction in asthma
Release of preformed histamine granules
Generation of leukotrienes C4, D4, E4
Leads to bronchoconstriction, inflammation, edema
Describe the late-phase reaction in asthma
Inflammation, especially major basic protein derived from eosinophils, damages cells and perpetuates bronchoconstriction
Asthma: Presentations
Episodic and related to allergen exposure
dyspnea, wheezing; productive cough
Asthma: histology of sputum
Spiral-shaped mucus plugs (Curschmann spirals) and eosinophil-derived crystals (Charcot-Leyden crystals)
Non allergic causes of asthma
Exercise, viral infection, aspirin, occupational exposures
Diagnostic test for asthma
methacholine challenge
Bronchiectasis
Permanent dilation of bronchioles and bronchi; loss of airway tone results in air trapping
Causes (5) of bronchiectasis
- cystic fibrosis
- kartagener syndrome
- tumor or foreign body
- necrotizing infection
- allergic bronchopulmonary aspergillosis
Bronchiectasis: Presentation
cough, dyspnea, foul-smelling sputum
comlications include hypoxemia with cor pulmonale and secondary (AA) amyloidosis
Describe lab values for restrictive lung diseases (TLC, FVC, FEV1: FVC)
Decreased TLC
Decreased FVC
Increased FEV1/FVC ratio
What are the two broad categories of restrictive lung diseases?
- Interstitial disease of lung (most common)
- chest wall abnormalities
Poor muscular - polio, MG,
Poor structural - scoliosis, obesity
Idiopathic pulmonary fibrosis
Fibrosis of lung interstitium
Unknown etiology; likely related to cyclical lung injury; TGF-beta from injured pneumocytes induces fibrosis
What are secondary causes of interstitial lung fibrosis?
Drugs (Bleomycin, amiodarone)
Radiation therapy
Idiopathic pulmonary fibrosis: presentation
Progressive dyspnea and cough
Fibrosis on lung seen in subpleural patches (CT), but eventually results in diffuse fibrosis with end-stage “honeycomb” lung
Idiopathic pulmonary fibrosis: Histology
honeycomb lung
Idiopathic pulmonary fibrosis: treatment
lung transplantation
Pneumoconioses: 4 types
Coal Worker’s Pneumoconiosis
Silicosis
Berylliosis
Asbestosis
What is the basic mechanism of pneumoconioses?
Alveolar macrophages engulf foreign particles and induce fibrosis
Coal Worker’s Pneumoconiosis:
Exposure, Finding
Carbon dust (coal miners) Diffuse fibrosis (black lung)
No increased risk for TB or cancer
Caplan syndrome
Coal Worker’s Pneumoconiosis with Rheumatoi arthritis (cavitating rheumatoid nodules)
Anthracosis
mild exposure to carbon (e.g. pollution) results in collections of carbon-laden macrophages in upper lobes
Silicosis: Exposure, Finding
Silica (sandblasters, foundries and silica miners)
Fibrotic nodules in upper lobes of lung; “egg shell calcifications” of hilar lymph nodes
Contains collagen and quartz
Which pneumoconiosis is associated with TB? Why
Silicosis
Silica disrupts phagolysosomes and impair macrophages
Increasing susceptibility to TB
What are the complications of silicosis exposure?
Silicosis pneumoconiosis
TB
bronchogenic carcinoma
Berylliosis: Exposure and finding
Beryllium (beryllium miners, aerospace industry)
Noncaseating granulomas in the lung, hilar lymph nodes and systemic organs
Resembles sarcoidosis
What are the complications of beryllium exposure?
Berryliosis
Increased risk for lung cancer
Asbestosis: Exposure and finding
Asbestos fibers (construction workers, roofing, plumbers, shipyard workers)
Fibrosis of lung and pleura (plaques); “ivory white”, calcified pleural plaque pathognomonic (not precancerous)
Long, golden-brown fibers with associated iron resembling dumbbells(asbestos bodies)
Affects lower lobes
What are the complications of asbestosis exposure?
Increased risk for bronchogenic carcinoma and mesothelioma
What is the most common occupational disease?
Silicosis
Where does malignant mesothelioma arise from?
Serosa of pleura; encases the lung
Sarcoidosis
Systemic disease characterized by noncaseating granulomas in multiple organs; African American females
Unknown etiology; likely due to CD4+ helper T cell response
Granulomas most commonly involve hilar lymph nodes and lung
Sarcoidosis: Histology
Stellate inclusions (asteroid bodies) within giant cell of granulomas
What tissues are involved in Sarcoidosis in addition to the lungs?
Uvea (uveitis)
Skin (cutaneous nodules, erythema nodosum)
Salivary and lacrimal glands (mimic Sjogren)
Sarcoidosis: Presentation
Dyspnea or cough
Elevated ACE
Hypercalcemia (1-alpha hydroxylase of epithelioid histiocytes)
Sarcoidosis: Treatment
steroids; often resolves spontaneously without treatment
Sarcoidosis Skin nodules: biopsy
granulomas
What is the most common noninfectious granulomatous disease of the liver?
Sarcoidosis
Sarcoidosis causes what lab abnormalities?
Increased ACE, Hypercalcemia (hypervitaminosis D)
Hypersensitivity pneumonitis
Granulomatous reaction to inhaled organic antigens
Presents as fever, cough, dyspnea after exposure; resolves with removal of exposure
Chronic exposure can lead to interstitial fibrosis
What are some collagen vascular diseases with interstitial fibrosis?
Systemic sclerosis
SLE
RA
What disease to suspect for pleural effusion in young woman?
SLE
Any unexplained pleural effusion in a young woman is SLE until proven otherwise
Pleural fluid contains inflammatory infiltrate, lupus erythematosus cells; presence of serositis
Farmer’s lung
Hypersensitivity pneumonitis
Exposure to Saccharopolyspora rectivirgula (thermophilic actinomyces) in moldy hay
What type of hypersensitivity is Farmer’s lung?
Type 3 and 4
Silo filler’s disease
Inhalation of gases (oxides of nitrogen) from plant material
Immediate hypersensitivity associated with dyspnea
Byssinosis
Contact with cotton, linen, hemp products
“Monday morning blues”
Acute Respiratory Distress Syndrome
Diffuse damage to alveolar-capillary interface (diffuse alveolar damage)
Leakage of protein-rich fluid leads to edema and formation of hyaline membranes in alveoli
ARDS: Clinical features and X-Ray
hypoxemia and cyanosis with respiratory distress - thickened diffusion barrier and collapse of air sacs (increased surface tension
White-out on chest x-ray
Causes of ARDS
Sepsis, infection, shock, trauma, aspiration, pancreatitis, DIC, hypersensitivity reactions, drugs
Activation of neutrophils induces protease-mediated and free radical damage of type I and II pneumocytes
ARDS: treatment
address underlying cause
PEEP
Recovery may be complicated by interstitial fibrosis (damage and loss of type II pneumocytes lead to fibrosis and scarring)
Neonatal respiratory distress syndrome
Inadequate surfactant levels
Lack of surfactant leads to collapse of air sacs and formation of hyaline membranes
What are some of the associations/causes of neonatal respiratory distress syndrome?
Prematurity (surfactant begins production at week 28)
C-section (lack of stress-induced steroids)
Maternal diabetes (insulin decreases surfactant production)
Neonatal respiratory distress syndrome: clinical features
increasing respiratory effort after birth; tachypnea with use of accessory muscles and grunting
hypoxemia with cyanosis
diffuse granularity of the lung (ground glass appearance) on x ray
Neonatal respiratory distress syndrome: complications
hypoxemia increases risk of persistant patent ductus arteriosus and necrotizing enterocolitis
Supplemental O2 increases risk for free radical injury - blindness, bronchopulmonary dysplasia
What is retinopathy of prematurity?
Inappropriate proliferation of vessels in inner layers of retina - increased VEGF
What is the most common cause of cancer mortality in US?
Lung (age 60)
Key risk factors for lung cancer
smoking (85% of lung cancer), radon asbestos
What is the second most common cause of lung cancer in US?
Radon exposure
Radioactive decay of uranium (in soil) - closed spaces such as basements
Responsible for most public exposure to ionizing radiation; also seen in uranium miners
Symptoms of lung cancer
not specific - cough, weight loss, hemoptysis, postobstructive pneumonia
Lung cancer: imaging
coin-lesion (solitary nodule) - biopsy necessary for diagnosis
What are some examples of benign “coin-lesions” in the lung?
Granulomas (TB, fungus) Bronchial hamartoma (benign tuor of lung and cartilage)
What are the two major categories of lung carcinoma?
Small cell 15% - not amenable to surgical resection
Non small cell (85%) - surgical resection
Describe TNM staging for lung carcinoma
T = tumor size and local extension
Pleural involvement; obstruction of SVC; recurrent laryngeal or phrenic; horner’s syndrome
N=spread of regional lymph nodes (hilar and mediatinal)
M = unique site of distant metastasis (adrenal gland)
Which organ does lung carcinoma spread to?
Adrenal gland
Small cell carcinoma: histology
poorly differentiated small cells from neuroendocrine (Kulchitsky) cells
Small cell carcinoma: association and location?
Male smokers
Central
Small cell carcinoma: Paraneoplastic syndromes?
ADH
ACTH
Eaton-Lambert syndrome
Small cell carcinoma: prognosis and metastasis
rapid growth and early metastasis
Squamous cell carcinoma of lung: histology
keratin pearls or intracellular bridges
Squamous cell carcinoma of lung: Association and location
Most common tumor in male smokers
Central
Squamous cell carcinoma of lung: Secretion?
PTHrP
Adenocarcinoma of lung: histology
glands or mucin
Adenocarcinoma of lung: Association and location
Most common in nonsmokers and female smokers
Peripheral
Large cell carcinoma of lung: histology
poorly differentiated large cells (no keratin pearls, intercellular bridges, glands or mucin)
Large cell carcinoma of lung: Association and location
Smoking
Central or peripheral
Large cell carcinoma of lung: Prognosis
Poor
Bronchioalveolar carcinoma: Histology
Columnar cells that grow along preexisting bronchioles and alveoli
Arise from Clara cells
Bronchioalveolar carcinoma: Association and location
Not related to smoking
Peripheral
Bronchioalveolar carcinoma: imaging and prognosis
Pneumonia-like consolidation
Excellent prognosis
Carcinoid tumor of the lung: Histology
Well differentiated neuroendocrine cells; chromogranin positive
Carcinoid tumor of the lung: association and location
Not related to smoking
Central or peripheral; classically forms a polyp-like mass in bronchus
Carcinoid tumor of the lung: Prognosis
Low-grade
Rarely, can cause carcinoid syndrome
What are the most common metastasis to the lung?
Breast and colon
Lung metastasis: x-ray
multiple cannon ball nodules on imaging
What is the most common tumor of the lung?
metastasis
What mutation is common in adenocarcinoma?
K-ras
Definition of pulmonary hypertension
>25 mmHg; normal is 10 mmHg
Atherosclerosis of pulmonary trunk, smooth muscle hypertrophy of pulmonary arteries and intimal fibrosis
Histology of severe, long-standing pulmonary hypertension
Plexiform lesions
Pneumothorax
accumulation of air in pleural spaace
What are the two types of pneumothorax?
Spontaneous and tension
Spontaneous pneumothorax
Rupture of emphysematous bleb, in young adults
Collapse of portion of lung
Does the trachea deviates to or away from spontaneous pneumothorax
Shifts to the side of collapse
Tension pneumothorax
Penetrating chest wall injury
Air enters pleural space, but cannot exit
Does trachea deviates to or away from trachea of tension pneumothorax?
Opposite side
Tension pneumothorax: treatment
insertion of chest tube
Mesothelioma
malignant neoplasm of mesothelial cells; high associated with occupationl exposure
Recurrent pleural effusions, dyspnea, chest pain; tumor encases the lung
