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373 Cards in this Set

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Calculate the A-a gradient in a patient breathing 0.30 O2 who has a Pco2 of 80 mm Hg and Pao2 of 40 mm Hg?
PAo2 = 0.30 (713) - 80/0.8 = 114 mm Hg. A-a gradient = 114 - 40 = 74 mm Hg, which is medically significant and indicates one or more of the above-mentioned lung disorders or a right-to-left shunt in the heart.
Calculate the a-a gradient in a patient breathing room air who has a Pco2 of 80 mm Hg and Pao2 of 40 mm Hg? What is happening?
PAo2 = 0.21 (713) - 80/0.8 = 50 mm Hg. A-a gradient = 50 - 40 = 10 mm Hg, which excludes the lung as the cause of the hypoxemia and indicates an extrapulmonary cause of hypoxemia.
When does the A-a gradient increase? Remain normal even though there is an abnormality?
(1) Hypoxemia due to pulmonary causes increases A-a gradient.
(2) Hypoxemia due to extrapulmonary causes has a normal A-a gradient.
How is the PAo2 calculated?
1) PAo2 = % O2 (713) - arterial Pco2/0.8
2) % O2 is the percentage of O2 the patient is breathing; 713 is the atmospheric pressure (760 mm Hg) minus the water vapor pressure (47 mm Hg); and 0.8 is the respiratory quotient.
When is the A-a gradient clinically significant?
1) Medically significant A-a gradient ≥ 30 mm Hg
(a) A-a gradient normally increases with age.
(b) A-a ≥ 30 mm Hg is set for highest specificity
List some Causes of hypoxemia with an increased a-a gradient?
a. Ventilation defect
(1) Impaired O2 delivery to the alveoli for gas exchange
(2) Example-airway collapse due to the respiratory distress syndrome
b. Perfusion defect
(1) Decreased or absent blood flow to the alveoli
(2) Example-pulmonary embolus
c. Diffusion defect
(1) O2 cannot diffuse through the alveolar-capillary interface.
(2) Examples-interstitial fibrosis, pulmonary edema
d. Right-to-left cardiac shunt
Example-tetralogy of Fallot
List some Causes of hypoxemia with a normal a-a gradient?
a. Depression of the respiratory center in the medulla
(1) Examples-barbiturates, brain injury
b. Upper airway obstruction
(1) Epiglottitis due to Haemophilus influenzae
(2) Croup due to parainfluenza virus
(3) Mucosal edema narrows the trachea.
c. Chest bellows (muscles of respiration) dysfunction
(1) Paralyzed diaphragm
(2) Amyotrophic lateral sclerosis with degeneration of anterior horn cells
Is spirometry a direct measure of all lung volumes? What is the function residual capacity?
1) does NOT directly measure FRC, RV, TLC
2) Total amount of air in the lungs at the end of a normal expiration
What is tidal volume?
Volume of air that enters or leaves the lungs during normal quiet respiration
What is FVC?
1) FVC is the total amount of air expelled after a maximal inspiration.
a. Normal FVC is 5 L
What is FEV1 second?
Forced expiratory volume in 1 second (FEV1 sec)
(1) Amount of air expelled from the lungs in 1 second after a maximal inspiration
(2) Normal FEV1 sec is 4 L
What is the normal FEV1/FVC?
Ratio of FEV1 sec/FVC is normally 4/5, or 80%
What is expiratory reserve volume?
1) ERV refers to the amount of air forcibly expelled at the end of a normal expiration.
2) ERV is commonly used to calculate residual volume (FRC - ERV = RV)
What is seen on the flow volume loop curve of someone with obstructive lung disease?
1) TLC is increased (e.g., ∼8.5 L) and RV is increased (e.g., 4 L).
2) Expiratory curve is shifted to the left of the normal curve.
3) Decreased PEF
4) Nonuniform emptying of the airways
How is the Flow-volume loop curve in restrictive parenchymal disease seen?
1) TLC is decreased (e.g.,∼4 L).
2) RV is decreased (e.g.,∼0.3 L).
3) Expiratory curve is shifted to the right of the normal curve.
4) Expiratory curve is narrow because of decreased lung volumes.
What are receptors that lead to dyspnea? What causes dyspnea?
1) Difficulty with breathing due to stimulation of J receptors causing decrease in full inspiration
2) Decreased compliance (e.g., interstitial fibrosis)
3) Increased airway resistance (e.g., chronic bronchitis)
4) Chest bellows disease (e.g., obesity, kyphoscoliosis)
5) Interstitial inflammation/fluid accumulation (e.g., left-sided heart failure)
Where are cough receptors located? Cough with a normal chest x-ray is most likely from what?
1) Cough receptors: located at bifurcations in airways, larynx, distal esophagus
2) Postnasal discharge is the most common cause
Note: When triggered, impulses travel via the internal laryngeal nerve, a branch of the superior laryngeal nerve which stems from the (vagus nerve) (CN X), to the medulla of the brain
What is a nocturnal cough present with?
1) GERD: due to acid reflux in tracheobronchial tree at night
2) Bronchial asthma: due to bronchoconstriction
What are causes of a productive cough?
1) Chronic bronchitis: due to smoking cigarettes
2) Typical bacterial pneumonia
3) Bronchiectasis
Which drugs can cause a cough?
1) ACE inhibitors: inhibit degradation of bradykinin; causes mucosal swelling and irritation in tracheobronchial tree
2) Aspirin: causes an increase in LT C-D-E4 (bronchoconstrictors)
What are some mechanisms for hemoptysis?
1) Parenchymal necrosis
2) Bronchial and/or pulmonary vessel damage
Hemoptysis can be caused by what?
1) Chronic bronchitis (most common cause)
2) Pneumonia, bronchogenic carcinoma
3) TB, bronchiectasis, aspergilloma (fungus living in a cavitary lesion)
What is the normal respiratory rate? tachypnea? What are causes of tachypnea?
1) Normal respiratory rate: 14-20 breaths per minute (bpm) in adults; up to 44 bpm in children
2) Tachypnea: rapid shallow breathing (>20 bpm)
3) Causes: restrictive lung disease; pleuritic chest pain; pulmonary embolus with infarction (key finding)
Causes of a tracheal shift include what?
1) Pressure in contralateral lung: large tension pneumothorax, large pleural effusion
2) Decreased volume in ipsilateral lung: large spontaneous pneumothorax, resorption atelectasis
What is vocal tactile fremitus?
Palpable thrill (vibration) transmitted through chest when patient says "E" or "1, 2, 3" or "99"
Which conditions present with decreased tactile fremitus?
1) emphysema or asthma, with increased AP diameter from an increase in total lung capacity
2) Also pleural effusion and atelectasis
Which conditions present with absent tactile fremitus?
atelectasis (collapse of airways); fluid (effusion); air (pneumothorax) in pleural space
Which conditions present with increased tactile fremitus?
(sound travels well through consolidations) with alveolar consolidation (e.g., lobar pneumonia)
Dullness on percussion may indicate what?
pleural effusion; lung consolidation; atelectasis (no air in the alveoli)
Hyperresonance on percussion is found in what conditions?
with pneumothorax; asthma; emphysema
Where is the site for normal airway resistance? Where does the site for laminar flow begin?
1) segmental bronchi (turbulent air flow)
2) begins at the terminal bronchioles-"small airway"
In asthma and chronic bronchitis there is small airway inflammation. What is the result?
air trapping, wheezing, increased airway resistance
Bronchial breathe sounds are always what?
always an abnormal sound
How do bronchial and tracheal breaths sound?
1) Loud, high-pitched sound with a peculiar hollow or tubular quality
2) Expiratory sounds longer than inspiratory
What is the significance of bronchial breathe sounds? What is the mechanism with which they appear? What is seen on a bronchogram?
1) Significance: consolidation (e.g., lobar/bronchopneumonia)
2) Mechanism: bronchi must be patent and partially collapsed
3) Associated with an "air bronchogram": air-filled bronchi silhouetted against airless consolidated parenchyma
Where are vesicular breath sounds heard? What is the length of inspiration to expiration?
1) Normal breath sounds: tracheal sounds that are modified (filtered) in alveoli
2) Sites: most lung fields except trachea and central bronchi
3) Inspiratory-to-expiratory ratio is 3:1
In what conditions are vesicular sounds present in? diminished in? increased in?
1) Present in: normal lungs; chronic bronchitis; emphysema
2) Diminished in: emphysema and asthma due to increased AP diameter
3) Absent in: pneumothorax; atelectasis; effusion
how are bronchovesicular breath sounds characterized?
1) Normal breath sounds heard over main bronchi
2) Abnormal if heard in lung periphery
3) Inspiratory and expiratory breath sounds are equal in length
crackles usual occur on inspiration. What causes early to midinspiratory crackles? Are they cleared with a cough?
1) Early and midinspiratory crackles: due to secretions in proximal large to medium-sized airways (e.g., chronic bronchitis);
2) clear with coughing
What causes late inspiratory crackles? Are they cleared with a cough?
1) Late inspiratory crackles: due to reopening of distal airways partially occluded by increased interstitial pressure (e.g., interstitial fluid-pus, transudate in CHF); do not clear with coughing; vary from fine to coarse
What conditions cause crackles?
pulmonary edema; lobar pneumonia; interstitial fibrosis (e.g., sarcoidosis)
What is wheezing? Is it usually heard on inspiration or expiration?
high-pitched musical sound usually heard in expiration; sometimes inspiration and expiration; expiration longer than inspiration
Wheezing can be caused by what?
inflammation segmental bronchi, small airways (e.g., asthma, chronic bronchitis); pulmonary edema constricting airway (called cardiac asthma); pulmonary infarction (release of TXA2 from platelets in embolus causes bronchoconstriction)
What are rhonchi? Can they be cleared with a cough?
low-pitched snoring sound heard during inspiration or expiration; due to secretions in large airways (bronchus, trachea); usually clear with coughing; common in chronic bronchitis
What is inspiratory stridor? What is causes it?
1) high-pitched inspiratory sound; sign of upper airway obstruction
2) epiglottitis (Haemophilus influenzae); croup (parainfluenza virus)
Someone with inspiratory and expiratory strider most likely has what?
sign of fixed upper airway obstruction (e.g., from cancer)
Why do pleural friction rubs occur? Do they occur on inspiration or expiration? When do they disappear? What diseases cause them?
1) two inflamed surfaces (pleural and parietal) rubbing against each other
2) Timing: end of inspiration and early part of expiration
3) Disappears: large effusion is present (separates inflamed surfaces); holding breath (continues with pericardial friction rub)
4) Causes: pleuritis due to cancer, infarction, pneumonia, serositis (SLE)
Is grunting in a newborn common?
always abnormal after 24 hours; common finding in RDS
In the normal lung how are spoken syllables heard? In alveolar consolidation? With egophony?
1) spoken syllables or numbers (e.g., 99) are indistinctly heard
2) syllables/numbers heard louder and more distinctly
3) patient saying "E" sounds like "A"
Is the FEV1 sec/FVC increased or decreased in a restrictive lung disease? What about obstructive?
1) normal to increased
2) decreased
In choanal atresia what occurs?
1) Unilateral or bilateral bony septum between the nose and the pharynx
2) Newborn turns cyanotic when breast-feeding.
3) Crying causes the child to "pink up" again.
4) child can't breath through nose
What are nasal polyps? How do they develop?
1) non-neoplastic tumefactions
2) Develop as a response to chronic inflammation
What is the most common polyp?
1) allergic polyps
2) Most often seen in adults with a history of IgE-mediated allergies
What are nasal polyps associated with?
aspirin and other nonsteroidal drugs
what is the asthma triad? Who does it primarily occur in?
1) aspirin, nasal polyp, asthma
2) Most often occur in women with chronic pain syndromes
Pathologically what occurs with nasal polyps associated with NSAIDs?
1) Drugs block cyclooxygenase leaving the lipoxygenase pathway open.
(2) Leukotrienes (LT) C-D-E4 are increased, causing bronchoconstriction
Children with nasal polyps should have what test performed?
order a sweat test to rule out cystic fibrosis
What is obstructive sleep apnea? What causes it?
1) Excessive snoring with intervals of breath cessation (apnea)
2) Obesity (very common)
a. Pharyngeal muscles collapse due to the weight of tissue in the neck.
3) Tonsillar hypertrophy, nasal septum deviation
What are clinical findings with obstructive sleep apnea?
1) Excessive snoring with episodes of apnea
2) Daytime somnolence often simulating narcolepsy
What are complications of obstructive sleep apnea?
1) Pulmonary hypertension (PH) leading to right ventricular hypertrophy
a. Called cor pulmonale
2) Secondary polycythemia
a. Due to a hypoxemic stimulus for erythropoietin release
What is the confirmatory test for obstructive sleep apnea?
Confirmatory test that documents periods of apnea during sleep is Polysomnography
Which sinus is most often inflamed in adults? In children?
1) Maxillary sinus is most often involved in adults.
2) Ethmoid sinus is most often involved in children.
What is the most common cause of sinusitis?
viral infection
Common pathogens causing sinusitis include? Which species commonly infects diabetics?
(1) Rhinoviruses
(2) Streptococcus pneumoniae (most common)
(3) Anaerobes (chronic sinusitis)
(4) Systemic fungi (e.g., Mucor or Aspergillus species)
a. Diabetics commonly have sinusitis due to Mucor species
What are clinical findings with sinusitis?
1) Fever
2) Nasal congestion
3) Pain over sinuses
4) Postnasal drip
How is sinusitis diagnosed?
1) Gold standard for bacterial culture is sinus aspiration
2) Sinus radiographs
3) CT scan is the most sensitive test.
4) Recommended if surgery is an option
How is sinusitis treated?
1) Decongestants
Antimicrobial therapy
a. Recommendation is not to use antibiotics.
b. Most cases are viral and resolve within 2 weeks
c. If resolution does not occur, antibiotics often used include the following:
Amoxicillin (most common drug), erythromycin, trimethoprim-sulfamethoxazole (TMP/SMX)
Who does nasopharyngeal carcinoma occur in?
1) Most common malignant tumor of the nasopharynx
2) Male dominant
3) Increased incidence in the Chinese and African populations
What is nasopharyngeal carcinoma associated with?
Causal relationship with Epstein-Barr virus (EBV)
What are pathologic findings in nasopharyngeal carcinoma?
1) Squamous cell carcinoma or undifferentiated cancer
2) Metastasizes to cervical lymph nodes
Does laryngeal carcinoma occur more in men or women? What are risk factors? Where do the majority occur?
1) More common in men than in women
Risk factors
(1) Cigarette smoking (most common cause)
(2) Alcohol (synergistic effect with smoking)
(3) Squamous papillomas and papillomatosis
a. Human papillomavirus type 6 and 11 association
4) Majority are located on the true vocal cords
What are the majority of laryngeal carcinomas? What are clinical findings?
1) keratinizing squamous cell carcinomas
2) Persistent hoarseness is often associated with cervical lymphadenopathy.
What is atelectasis?
Loss of lung volume due to inadequate expansion of the airspaces (collapse)
Pathologically what occurs to produce atelectasis?
1) Airway obstruction by thick secretions prevents air from reaching the alveoli.
2) Obstruction occurs in bronchi, segmental bronchi, or terminal bronchioles.
3) Causes of obstruction
a. Mucus or mucopurulent plug after surgery
b. Aspiration of foreign material
c. Centrally located bronchogenic carcinoma
4) Lack of air and distal resorption of preexisting air through the pores of Kohn in the alveolar walls
5) Collapse may involve all or part of a lung.
Clinically how does someone present with resorption atelectasis?
1) Fever and dyspnea
2) Both usually occur within 24 to 36 hours of collapse.
3) Absent breath sounds and dullness to percussion
4) Absent vocal vibratory sensation (tactile fremitus)
5) Alveoli are collapsed.
6) Ipsilateral elevation of the diaphragm and tracheal deviation
a. Only occurs if large areas of the lung are atelectatic
7) Collapsed lung does not expand on inspiration (inspiratory lag)
How is resorption atelectasis treated?
1) Incentive spirometry after surgery
2) Positive-pressure breathing (CPAP) by face mask
3) Positive end-expiratory pressure (PEEP) on mechanical ventilation
What is compression atelectasis?
1) Air or fluid in the pleural cavity under increased pressure collapses small airways beneath the pleura.
2) Examples:
a.Tension pneumothorax where air compresses the lung
b. Pleural effusion where fluid compresses the lung
Where is surfactant made? What is the main component? When does it begin to be made?
1) Synthesized by type II pneumocytes
a) Stored in lamellar bodies
b) Synthesis begins in 28th week of gestation.
2) Phosphatidylcholine (lecithin) is the major component
Which hormones increase surfactant production? Which decrease it?
1) Synthesis is increased by cortisol and thyroxine, prolactin
2) Synthesis is decreased by insulin.
What are 3 things that can lead to RDS in a newborn?
(a) Prematurity
(b) Maternal diabetes
1. Fetal hyperglycemia increases insulin release.
(c) Cesarean section
2. Lack of stress-induced increase in cortisol from a vaginal delivery
what are collapsed alveoli from RDS in a newborn lined by?
1) lined by hyaline membranes
2) Derived from proteins leaking out of damaged pulmonary vessels
What are clinical findings in RDS?
(1) Respiratory difficulty begins within a few hours after birth.
(2) Grunting
(3) Tachypnea
(4) Intercostal retractions
(5) Infants develop hypoxemia and respiratory acidosis.
how is RDS in a newborn diagnosed? how is it treated?
1) Chest radiograph shows a "ground glass" appearance
2) CPAP therapy with endotracheal tube with O2 and surfactant
What are complications that occur as a result of RDS?
(1) Superoxide free radical damage from O2 therapy
a. May result in blindness and permanent damage to small airways (bronchopulmonary dysplasia)
(2) Intraventricular hemorrhage
(3) Patent ductus arteriosus
a. Due to persistent hypoxemia
(4) Necrotizing enterocolitis
a. Intestinal ischemia allows entry of gut bacteria into the intestinal wall.
(5) Hypoglycemia in newborn
a. Excess insulin decreases serum glucose, producing seizures and damage to neurons.
b. Must give newborns glucose to prevent hypoglycemia
Whats the most common cause of pulmonary edema due to Starling pressures? What are others due to Starling pressures?
1) Left-sided heart failure (most common), volume overload, mitral stenosis
2) Decreased oncotic pressure
a. Nephrotic syndrome, cirrhosis
What are causes of pulmonary edema due to microvascular or alveolar injury?
1) Infections
Examples-sepsis, pneumonia
2) Aspiration
Examples-drowning, gastric contents
3) Drugs
4) High altitude
5) Acute respiratory distress syndrome
What is ARDS?
Noncardiogenic pulmonary edema resulting from acute alveolar-capillary damage
Risk factors for ARDS include?
(1) Gram-negative sepsis (>40% of cases)
(2) Gastric aspiration (>30% of cases)
(3) Severe trauma with shock (>20% of cases)
(4) Diffuse pulmonary infections
a. Severe acute respiratory syndrome (SARS), hantavirus
(5) Heroin
(6) Smoke inhalation
(7) Acute pancreatitis
(8) Cardiopulmonary bypass
(9) Disseminated intravascular coagulation
(10) Amniotic fluid embolism, fat embolism
Pathologically what occurs in ARDS?
a. Acute damage to alveolar capillary walls and epithelial cells
b. Alveolar macrophages and other cells release cytokines.
(1) Cytokines are chemotactic to neutrophils.
(2) Neutrophils transmigrate into the alveoli through pulmonary capillaries.
(3) Capillary damage causes leakage of a protein-rich exudate producing hyaline membranes.
(4) Neutrophils damage type I and II pneumocytes.
*Decrease in surfactant causes atelectasis with intrapulmonary shunting.
c. Late findings
(1) Repair by type II pneumocytes
(2) Progressive interstitial fibrosis (restrictive lung disease)
How does ARDS present on physical exam?
1) Dyspnea/tachypnea
2) Late inspiratory crackles
What is the most common cause of ARDS?
sepsis most common cause
When testing for ARDS what will be seen in blood work and on chest x-ray?
1) Severe hypoxemia not responsive to O2 therapy
2) Pulmonary artery wedge pressure < 18 mm Hg
a. Important in distinguishing ARDS from cardiogenic pulmonary edema
3) Respiratory alkalosis or normal Paco2
4) Increased a-a gradient, due to:
a. Intrapulmonary shunting
b. Related to atelectasis
c. Diffusion abnormalities
d. Related to hyaline membranes, alveolar infiltrate
5) Chest x-ray
a. Bilateral interstitial infiltrates initially
b. Progresses to widespread alveolar consolidation with air bronchograms (80%)
How is ARDS treated and what is the prognosis?
1) Treat underlying disease
2) Hemodynamic monitoring
3) Mechanical ventilation
4) Nitric oxide inhalation
5) Corticosteroids
6) Poor prognosis (40-50% mortality rate)
What is the most common cause of typical community-acquired pneumonia?
Streptococcus pneumoniae
What are two ways typical pneumonia is acquired?
(1) Inhalation of aerosol from an infected patient
(2) Aspiration of nasopharyngeal flora while sleeping
How does bronchopneumonia begin? How does it progress?
(1) Begins as an acute bronchitis and spreads locally into the lungs
(2) Usually involves the lower lobes or right middle lobe
(3) Lung has patchy areas of consolidation
(4) Microabscesses are present in the areas of consolidation
What is lobar pneumonia?
Complete or almost complete consolidation of a lobe of lung
a. occurs in typical pneumonia
What are complications of typical pneumonia?
(1) Lung abscesses, empyema (pus in the pleural cavity)
(2) Sepsis
During the physical exam what would signs of consolidation be?
(a) Dullness to percussion
(b) Increased vocal tactile fremitus
*Sound is transmitted well through alveolar consolidations.
(c) Late inspiratory crackles
(d) Bronchial breath sounds
(e) Bronchophony and egophony
What are clinical findings in typical pneumonia?
(1) Sudden onset of high fever with productive cough
(2) Chest pain
(3) Tachycardia
(4) Signs of consolidation (alveolar exudate)
(5) Chest radiograph (gold standard screen)
(a) Patchy infiltrates (bronchopneumonia) or lobar consolidation
(b) Sensitivity 50% to 85%
What do cultures and CBCs show in someone with typical pneumonia?
1) Positive Gram stain
a. More useful than culture
b. Cultures are still obtained.
c. Sensitivity 80%
2) Neutrophilic leukocytosis
3) Blood cultures positive in 20% of cases.
Atypical pneumonia is caused by what?
(1) Usually caused by Mycoplasma pneumoniae
(2) Other pathogens
(a) Chlamydophilia pneumoniae
(b) Viruses
Respiratory syncytial virus, influenzavirus, adenovirus
(c) Chlamydia trachomatis in newborns
(d) legionella
How is atypical pneumonia characterized?
Patchy interstitial pneumonia
(1) Mononuclear infiltrate
(2) Alveolar spaces usually free of exudate
What are clinical findings in someone with atypical pneumonia?
(1) Insidious onset, low-grade fever
(2) Nonproductive cough
(3) Chest pain
(4) Flu-like symptoms
a. Pharyngitis, laryngitis, myalgias, headache
(5) No signs of consolidation
What are risk factors in nosicomial pneumonia?
(1) Severe underlying disease
(2) Antibiotic therapy
(3) Immunosuppression
(4) Respirators
a. Most common source of infection
What are the pathogens in nosicomial pneumonia?
(1) Gram-negative bacteria
a. Pseudomonas aeruginosa (respirators), Escherichia coli
(2) Gram-positive bacteria (e.g., Staphylococcus aureus)
What are common causes of pneumonia in an immunocompromised person?
(1) Cytomegalovirus
(2) Pneumocystis jiroveci is most common in AIDS
a. Trimethoprim-sulfamethoxazole is used for prophylaxis and treatment.
(3) Aspergillus fumigatus
How is TB contracted? How does it evade the immune system? What type of organism is it? What is virulence factor?
(1) Contracted by inhalation of Mycobacterium tuberculosis
(2) Organism resides in phagosomes of alveolar macrophages
a. Produces a protein that prevents fusion of lysosomes with phagosome
(3) Characteristics
(a) Strict aerobe, acid-fast (due to mycolic acid in cell wall)
(b) Cord factor is virulence factor
How is TB screened?
(a) Purified protein derivative (PPD) intradermal skin test
(b) Does not distinguish active from inactive disease
How does resistance in TB occur?
(a) Chromosome mutations involving mycolic acid
(b) Chromosome mutations involving catalase peroxidase
*Enzyme is required to activate isoniazid
How is primary TB characterized? Where does it grow in the lungs?
(1) Subpleural location
(a) Upper part of the lower lobes or lower part of the upper lobes
(b) Ghon focus (caseous necrosis) in periphery
(c) Ghon complex (caseous necrosis) in hilar lymph nodes
(2) Usually resolves
(a) Produces a calcified granuloma or area of scar tissue
(b) May be a nidus for secondary TB
how is secondary TB characterized?
(1) Due to reactivation of a previous primary TB site
(2) Involves one or both apices in upper lobes
a. Ventilation (oxygenation) is greatest in the upper lobes.
(3) Cavitary lesion due to release of cytokines from memory T cells
What are clinical findings in TB?
Fever, drenching night sweats, weight loss
What are complications of TB?
(1) Miliary spread in lungs due to invasion into the bronchus or lymphatics
(2) Miliary spread to extrapulmonary sites
(a) Due to invasion of pulmonary vein tributaries
(b) Kidney is the most common extrapulmonary site.
(c) Adrenal involvement may result in Addison's disease.
(3) Massive hemoptysis, bronchiectasis, scar carcinoma
(4) Granulomatous hepatitis, spread to vertebra (Pott's disease)
How is TB diagnosed?
(1) Bronchoalveolar lavage best for staining and culture
(2) Sputum cultures
How is TB treated?
(1) Isoniazid + rifampin + pyrazinamide + ethambutol + vit B6
(2) Noninfectious in 2 to 3 weeks
(3) Treat for additional 9 to 12 months
a. Kills metabolically inactive persisters in lesions
What is Mycobacterium avium-intracellulare complex? Who is it most common in? How is it treated?
1) Atypical mycobacterium
2) Most common TB in AIDS (often disseminates)
3) Occurs when CD4 TH count falls below 50 cells/mm3
5) Treatment:
Clarithromycin + rifabutin + ethambutol
What do systemic fungal infections do in the lungs? How are they contracted?
1) Contracted from inhalation of the pathogen
2) Produce a granulomatous inflammatory reaction with or without caseation

Most lung abcesses are due to aspiration of oropharyngeal material. What are risk factors?
(a) Alcoholism
(b) Loss of consciousness
(c) Recent dental work
What are pathogens that cause lung abcesses?
(a) Aerobic and anaerobic streptococci
(b) Staphylococcus species
(c) Prevotella
(d) Fusobacterium
(e) mixed aerobic/anaerobic infection
Which organisms cause lung abscess as a result of bacterial pneumonia?
Staphylococcus aureus, Klebsiella pneumoniae
Lung abscesses as a result of aspiration are located where?
Superior segment, right lower lobe
What are clinical and diagnostic findings of a lung abscess?
1) Spiking fever with productive cough (foul-smelling sputum)
2) Chest imaging shows cavitation with an air-fluid level
Aspiration of foreign material in the standing or seated position goes where?
material localizes in the posterobasal segment of the right lower lobe
Aspiration of material in the supine position goes where?
the superior segment of the right lower lobe
Aspiration in a right sided position goes where?
the right middle lobe or the posterior segment of the right upper lobe
what is the most common cause of a cold? How is it transmitted? What are other organisms that cause a cold?
1) Rhinovirus
2) Transmitted by hand to eye-nose contact
3) Other causes of colds: coronaviruses, adenoviruses, influenza C virus, coxsackievirus
What does coxsackievirus do in the lungs?
Acute chest syndrome: fever with pleuritis
What is the Most common viral cause of atypical pneumonia and bronchiolitis (wheezing) in children? otitis media in older children? How can each be diagnosed? What is the passive immunity?
1) RSV
2) Occurs in late fall and winter
3) Rapid diagnosis with antigen detection in nasopharyngeal wash
4) Passive immunization: palivizumab (monoclonal antibody) reduces hospitalization rates
What is the Most common cause of laryngotracheobronchitis in infants? What is seen on clinical exam? What sign is present on x-ray? how is it treated?
1) croup (parainfluenza)
2) inspiratory stridor (upper airway obstruction) due to submucosal edema in trachea;
3) brassy cough; signs of respiratory distress
4) Anterior x-ray of neck shows "steeple sign," representing mucosal edema in the trachea (site of obstruction)
5) Bronchiolitis in infants
6) Treatment: cold water humidifiers and aerosolized racemic epinephrine
Histologically how is CMV characterized?
Enlarged alveolar macrophages/pneumocytes, contain basophilic intranuclear inclusions surrounded by a halo (owls eye)
Which influenza occurs more often? What are its virulence factors?
1) Type A viruses are most often involved
2) Hemagglutinins bind virus to cell receptors in the nasal passages
3) Neuraminidase dissolves mucus and facilitates release of viral particles
What does influenza A cause? Influenza B?
1) Influenza A: worldwide epidemics; pneumonia may be complicated by a superimposed bacterial pneumonia (usually Staphylococcus aureus)
2) Influenza B: causes major outbreaks
What are the major modes that influenza is able to change?
1) Antigen drift: minor mutation; does not require new vaccine
2) Antigen shift: major mutation in hemagglutinin or neuraminidase; new vaccine required (reassortment of 8 chromosomes)
Clinically how does influenza present? Who is vaccination mandatory in? How is it treated? What is influenza associated with?
1) Clinical: fever, headache, cough, myalgias, chest pain
2) Vaccination: mandatory for people > 65 years old, people with chronic illnesses
3) Treatment: neuraminidase inhibitors zanamivir, oseltamivir
4) Associations: Reye syndrome with salicylate ingestion; Guillain-Barré syndrome
Clinically how does Rubeola present? what is seen histologically?
1) Fever, cough, conjunctivitis, and excessive nasal mucus production
2) Koplik spots in the mouth precede onset of the rash
3) Warthin-Finkeldey multinucleated giant cells are a characteristic finding
How does SARS effect the lungs? How was it first transmitted? How is it diagnosed?
1) Infects lower respiratory tract and then spreads systemically
2) First transmitted to humans through contact with masked palm civets (China) and then from human-to-human contact through respiratory secretions (e.g., hospitals, families)
3) Develop severe respiratory infection
4) Diagnose with viral detection by PCR assay or detection of antibodies
What does hanta virus do in the body? how is transmitted? how is it diagnosed and treated?
1) Transmission: inhalation of urine/feces from deer mice in Southwestern United States
2) Pulmonary syndrome: ARDS, hemorrhage, renal failure
3) Diagnosis: detect viral RNA in lung tissue
4) No effective treatment
5) High mortality rate
The Second most common cause of atypical pneumonia is? What is it associated with? How is it treated?
1) Chlamydophilia pneumoniae
2) Seroepidemiologic association with coronary artery disease
3) Treatment: doxycycline
What does Chlamydia trachomatis cause in newborn? What are symptoms and how is it treated?
1) Newborn pneumonia (passage through birth canal)
2) Afebrile, staccato cough (choppy cough), conjunctivitis, wheezing
3) Treatment: erythromycin (Nathe says azythromycin)
Who is M. pneumoniae common in? What is presentation and complications? how is it treated and diagnosed?
1) Common in adolescents and military recruits (closed spaces)
2) Insidious onset with low-grade fever
3) Complications: bullous myringitis, cold autoimmune hemolytic anemia due to anti-I-IgM antibodies.
4) Treatment: erythromycin; azithromycin; clarithromycin
(nath says azythromycin or levofloxacin + ceftriaxone)
5) Cold agglutinins in blood
How is Coxiella burnetii transmitted? What is it associated with? What does it cause? How is it treated?
1) Usually transmitted without a vector
2) Contracted by dairy farmers, veterinarians
3) Associated with the birthing process of infected sheep, cattle, and goats, and handling of milk or excrement
4) Atypical pneumonia, myocarditis, granulomatous hepatitis
5) Treatment: doxycycline
6) intracellular, gram -
How is Streptococcus pneumoniae characterized? How does it present? What is an excellent screen test? How is it treated?
1) Gram-positive lancet-shaped diplococcus
2) Most common cause of typical community-acquired pneumonia
3) Rapid onset, productive cough, signs of consolidation
4) Urine antigen test excellent screen
5) Treatment: penicillin G; amoxicillin
What color sputum is found with s. aureus infection? What infection is it found with? What diseases? what does it cause? How is it treated?
1) Yellow sputum
2) Commonly superimposed on influenza pneumonia and measles pneumonia
3) Major lung pathogen in cystic fibrosis and IV drug abusers
4) Hemorrhagic pulmonary edema, abscess formation, and tension pneumatocysts (intrapleural blebs), which may rupture and produce a tension pneumothorax.
5) Treatment: TMP-SMX
What type organism is C diphtheriae? How is it pathogenic? What organ is affected? how is it treated?
1) Gram-positive rod with metachromatic granules
2) Toxin inhibits protein synthesis by ADP-ribosylation of elongation factor 2 involved in protein synthesis
3) Toxin also impairs β-oxidation of fatty acids in the heart
4) Toxin-induced pseudomembranous inflammation produces shaggy gray membranes in the oropharynx and trachea; toxic myocarditis (death)
5) Treatment: erythromycin
B anthracis is characterized as? What is it habitat? Virulence factors? How is it transmitted?
1) Gram-positive rod
2) Habitat: soil
3) Capsule inhibits phagocytosis
4) Exotoxins: edema factor (activates adenylate cyclase); lethal factor (inhibits a signal transduction protein involved in cell division); protective antigen (assists entry of above toxins into cells)
5) Transmission: direct contact with animal skins or products (most commonly sheep and cattle) and entry of the organisms through abrasions or cuts; inhalation (use in germ warfare)
What are the 2 types of anthrax? How is it prevented? How is it treated?
1) Cutaneous anthrax (90-95% of cases): occurs through direct contact with infected or contaminated animal products; resembles insect bite but eventually swells to form a black scab, or eschar, with a central area of necrosis ("malignant pustule"); if untreated, death occurs in 20% of patients
2) Pulmonary anthrax: "first sign of the disease is death"; inhalation of spores present in contaminated hides or germ warfare; necrotizing pneumonia, meningitis, pronounced splenomegaly, and dissemination throughout the rest of the body
3) Prevention: vaccine available for high-risk patients; e.g., veterinarians, soldiers entering developing countries
4) Treatment: ciprofloxacin
What is Actinomyces israeli? What does it produce? how is it treated?
1) Gram-positive filamentous bacteria; strict anaerobe; normal flora in tonsils and adenoids
2) Produces draining sinuses in the jaw, chest cavity, and abdomen; pus contains sulfur granules (yellow specks) that contain the bacteria
3) Treatment: ampicillin or penicillin G
Note: for comparison Nocardia is weakly-staining Gram-positive, catalase-positive, rod-shaped bacteria. It forms partially acid-fast beaded branching filaments
What is Nocardia asteroides? What does it do in lung? Where does it spread to? How is it treated?
1) Gram-positive filamentous bacteria; strict aerobe; partially acid-fast
2) Produces granulomatous microabscesses in the lungs
3) Frequently disseminates to the CNS and kidneys
4) Treatment: TMP-SMX
What is B pertussis? pathologically what does it do? What does it produce?
1) Gram-negative rod
2) Pili attach to cilia in upper respiratory tract; toxin stimulates adenylate cyclase, which catalyzes the addition of ADP-ribose to the inhibitory subunit of the G protein complex; toxin also produces absolute lymphocytosis (normal-appearing lymphocytes) often in leukemoid reaction range
3) Produces whooping cough, transmitted by droplet infection
What are the 3 phases of B pertussis?
1) Catarrhal phase: lasts 1-2 weeks; mild coughing, rhinorrhea, conjunctivitis
2) Paroxysmal coughing phase: lasts 2-5 weeks; characteristic 4-5 coughs in succession on expiration followed by an inspiratory whoop; absolute lymphocytosis (20,000-50,000 cells/mm3)
3) Convalescence phase: lasts 1-2 weeks; slow decline in coughing and lymphocytosis
What are complications of B pertussis? how is it diagnosed and treated?
1) Complications: hemorrhage into skin, conjunctiva, bronchus, brain from coughing; otitis media; meningoencephalitis (10%); rectal prolapse from coughing; pneumonia (most common cause of death in children < 3 years old; children < 1 year old have no protection from mother's immunoglobulins)
2) Diagnosis: nasopharyngeal swabs using special cough plate; direct immuno-fluorescence of swab material
3) Treatment: erythromycin
What is H influenzae? What is it the most common cause of? What does it cause? What sign is seen? How is it treated?
1) Gram-negative rod
2) Common cause of sinusitis, otitis media, conjunctivitis ("pinkeye")
3) Inspiratory stridor may be due to acute epiglottitis
4) Swelling of epiglottis produces "thumbprint sign" on lateral x-ray of the neck
5) Most common bacterial cause of acute exacerbation of COPD
6) Treatment: cefotaxime; ceftriaxone
What is M catarrhalis? What does it commonly cause and in who? How is it treated?
1) Gram-negative diplococcus
2) Common cause of typical pneumonia, especially in the elderly
3) Second most common pathogen causing acute exacerbation of COPD
4) Common cause of chronic bronchitis, sinusitis, otitis media
5) Treatment: amoxicillin-clavulanate
What is P aeruginosa? What type of mucus is seen? What is it the most common cause of? Where is it found and how is it treated?
1) Green sputum (pyocyanin)
2) Water-loving bacteria most often transmitted by respirators
3) Most common cause of nosocomial pneumonia and death due to pneumonia in cystic fibrosis
4) Pneumonia often associated with infarction due to vessel invasion
5) Treatment: piperacillin + tobromicin (gentamicin) + antipseudomonal quinolone or macrolide
6) Gram-negative, aerobic, rod-shaped bacterium with unipolar motility, alginate capsule, lactose fermentor and oxidase +
Klebsiella pneumoniae is what? Who is it common in? What does it cause? how is it treated?
1) Gram-negative fat rod surrounded by a mucoid capsule
2) Most common gram-negative organism causing lobar pneumonia and typical pneumonia in elderly patients in nursing homes
3) Common cause of pneumonia in alcoholics; however, S. pneumoniae is still the most common pneumonia
4) Atypical pneumonia associated with blood-tinged, thick, mucoid sputum
5) Lobar consolidation and abscess formation are common
6) Treatment: ceftriaxone
Legionella pneumophila is what? Seen with what stains? How are antigens detected? Where are the bacteria found? What are risk factors?
1) Gram-negative rod (requires IF stain or Dieterle silver stain to identify in tissue)
2) Antigens can also be detected in urine
3) Water-loving bacterium (water coolers; mists in produce section of grocery stores; outdoor restaurants in summer; rain forests in zoos)
4) Risk factors: alcoholic, smoker, immunosuppression
What is Legionella pneumophila associated with? What can it damage and lead to? How is it treated?
1) Pneumonia associated with high fever, dry cough, flu-like symptoms
2) May produce tubulointerstitial disease with destruction of the JG apparatus leading to hyporeninemic hypoaldosteronism (type IV renal tubular acidosis-hyponatremia, hyperkalemia, metabolic acidosis)
3) Urine antigen test excellent screen
4) Treatment: fluoroquinolone; azithromycin
Yersinia pestis is what? how is it transmitted? How does it resistant the immune system?
1) Gram-negative rod
2) Cause of plague
3) Transmitted by bite of rat flea; primary reservoir for bacteria are ground squirrels in the Southwest
4) Also transmitted person-to-person by droplet infection
5) Macrophages cannot kill bacteria due to protection by V and W antigens
What are the 3 types of yersinia pestis infection? How is it treated?
1) Three types of disease: bubonic (most common), pneumonic (transmitted by aerosol), septicemic
2) Bubonic type: bite by rat flea that has recently bitten an infected ground squirrel; infected lymph nodes enlarge (usually in the groin), mat together, and drain to the surface (buboes)
3) Treatment:
Pneumonic type: gentamicin + doxycycline
Bubonic type: gentamicin or streptomycin
How is Cryptococcus neoformans characterized? What is it found in? What does it cause and how is it treated?
1) Budding yeast with narrow-based buds; surrounded by a thick capsule.
2) Found in pigeon excreta (around buildings, outside office windows, under bridges)
3) Primary lung disease (40%): granulomatous inflammation with caseation
4) Treatment: fluconazole
Note: causes "soap bubble appearance in brain"
How is Aspergillus fumigatus characterized? What does it do in lung?
1) Fruiting body and narrow-angled (<45 degrees), branching septate hyphae
2) Aspergilloma: fungus ball (visible on x-ray) that develops in a preexisting cavity in the lung (e.g., old TB site); cause of massive hemoptysis
What happens in Allergic bronchopulmonary aspergillosis?
1) type I and type III hypersensitivity reactions; IgE levels increased; eosinophilia. Intense inflammation of airways and mucus plugs in terminal bronchioles. Repeated attacks may lead to bronchiectasis and interstitial lung disease; treatment with corticosteroids
2) Vessel invader with hemorrhagic infarctions and a necrotizing bronchopneumonia
3) Treatment: voriconazole
how are Mucor species characterized? Who do they infect? What do they infect? how is it treated?
1) Wide-angled hyphae (>45 degrees) without septa and appear empty
2) Clinical settings: diabetes, immunosuppressed patients
3) Vessel invader and produces hemorrhagic infarcts in the lung
4) Invades the frontal lobes in patients with diabetic ketoacidosis (rhinocerebral mucormycosis)
5) Treatment: amphotericin B
Coccidioides immitis is seen how? how is it contracted? What are symptoms? How is it treated?
1) Spherules with endospores in tissues
2) Contracted by inhaling arthrospores in dust while living or passing through arid desert areas in the Southwest (valley fever); increased after earthquakes (increased dust)
3) Flu-like symptoms and erythema nodosum (painful nodules on lower legs; inflammation of subcutaneous fat)
4) Granulomatous inflammation with caseous necrosis
5) Treatment: usually self-limited; if severe: itraconazole or fluconazole
What is the most common systemic fungal infection? Where is it endemic? How is it transmitted? What results?
1) Histoplasma capsulatum (identified by macrophages filled with yeast)
2) Endemic in Ohio and central Mississippi river valleys
3) Inhalation of microconidia in dust contaminated with excreta from bats (increased incidence in cave explorers, spelunkers), starlings, or chickens (common in chicken farmers)
4) Granulomatous inflammation with caseous necrosis
Histologically what is seen with H capsulatum? What does it mimic? Besides the lung what is affected? How is it treated?
1) Yeast forms are present in macrophages
2) Simulates TB lung disease; produces coin lesions, consolidations, miliary spread, and cavitation
3) Marked dystrophic calcification of granulomas; most common cause of multiple calcifications in the spleen
4) Treatment: usually self-limited; if severe, itraconazole or amphotericin B
How is Blastomyces dermatitidis characterized? where are they located? Who does it occur in? what do lesions mimic? What occurs in lung? How is it treated?
1) Yeasts have broad-based buds and nuclei
2) Occurs in Great Lakes region, central, and southeastern United States
3) Male dominant disease
4) Produces skin and lung disease; skin lesions simulate squamous cell carcinoma
5) Granulomatous inflammation with caseous necrosis
6) Treatment: itraconazole or amphotericin B
what does Pneumocystis jiroveci attack? When can someone be infected? What are symptoms? how is it prevented?
1) Cysts and trophozoites present; cysts attach to type I pneumocytes
2) Primarily an opportunistic infection; occurs when CD4 count < 200 cells/mm3.
3) Most common initial AIDS-defining infection
4) Patients develop fever, dyspnea, and severe hypoxemia
5) Treatment: TMP-SMX given prophylactically when CD4 counts < 200 cells/mm3
How is Pneumocystis jiroveci stained? What is seen? What is seen on chest x-ray?
1) Diffuse intra-alveolar foamy exudates with cup-shaped cysts best visualized with silver or Giemsa stains
2) Chest x-ray shows diffuse alveolar and interstitial infiltrates
Histologically how does C neoformans present?
The yeast form produces a clear capsule around a central faint nucleus.
Lung biopsy stained with Gomori methenamine-silver shows fruiting body with narrow-angled, branching septate hyphae. What is it?
Aspergillus fumigatus
Where do the majority of pulmonary embolisms originate?
Majority (95%) originate in the femoral vein
Potential consequences of pulmonary artery occlusion are what?
(1) Increase in pulmonary artery pressure
(2) Decrease blood flow to pulmonary parenchyma
a. May cause hemorrhagic infarction
What does a hemorrhagic infarct look like? Where are the majority located?
1) Red-blue, raised, wedge-shaped area that extends to the pleural surface
2) Pleural surface has a fibrinous exudate (produces a pleural friction rub).
3) Hemorrhagic pleural effusion may also occur.
4) Majority are located in the lower lobes.
a. Perfusion is greater than ventilation in the lower lobes.
What are clinical findings with a saddle embolus?
(1) Sudden increase in pulmonary artery pressure
(2) Produces acute right ventricular strain and sudden death
What are clinical findings with a pulmonary infarct?
(1) Sudden onset of dyspnea and tachypnea
(2) Fever
(3) Pleuritic chest pain (pain on inspiration)
(4) Pleural friction rub
(5) Pleural effusion
(6) Expiratory wheezing
a. Due to release of thromboxane A2 from platelets
What are laboratory findings with a pulmonary infarction?
1) Respiratory alkalosis (arterial Pco2 < 33 mm Hg)
2) Pao2 < 80 mm Hg (90% of cases)
3) Increase in a-a gradient (100% of cases)
4) Increase in d-dimers
What is the most common sign and symptom of a pulmonary infarct?
dyspnea and tachypnea most common symptom and sign; respiratory alkalosis; hypoxemia
A chest x-ray of someone with a pulmonary infarct would show what?
(1) Pleural effusion
(2) "Cut-off" sign of one or more pulmonary arteries
a. Hypovascularity behind the blocked vessel
(3) Hampton's hump
a. Wedge-shaped area of consolidation
What are various tests used to diagnose a PE?
(1) Ventilation scan is normal, but the perfusion scan is abnormal
(2) Pulmonary angiogram is gold standard confirmatory test.
a. Expensive and not clinically available in smaller hospitals
(3) Spiral (helical) CT is excellent if preexisting lung disease is present.
What is Usually performed in conjunction with ventilation/perfusion (V/Q) scan or spiral CT is someone with a PE?
What is the prognosis for a PE?
∼80% overall survival
∼60% resolve without treatment
∼90% resolve with treatment
how is pulmonary hypertension defined?
1) Mean pulmonary artery pressure > 25 mm Hg at rest
2) Mean pulmonary artery pressure > 30 mm Hg with exercise
With a pulmonary infarction is a ventilation scan normal? What perfusion scan? d-dimers?
normal ventilation scan, abnormal perfusion scan; ↑ d-dimers
Who is primary pulmonary hypertension more common in? What is the genetic predisposition?
(1) Primary type is more common in women.
(2) Genetic predisposition
a. Mutations in genes associated with transforming growth factor-β
(3) Vascular hyperreactivity with proliferation of smooth muscle
What is malfunctioning in secondary pulmonary hypertension?
(1) Endothelial cell dysfunction
(a) Loss of vasodilators (e.g., nitric oxide)
(b) Increase in vasoconstrictors (e.g., endothelin)
(2) Hypoxemia and respiratory acidosis stimulate vasoconstriction of pulmonary arteries.
a. Causes smooth muscle hyperplasia and hypertrophy
What are causes of secondary pulmonary hypertension?
1) Chronic hypoxemia
a. Examples-chronic lung disease; living at high altitude
2) Chronic respiratory acidosis
a. Chronic bronchitis (CB); obstructive sleep apnea
3) Loss of pulmonary vasculature
a. Increases workload for remaining vessels; emphysema, recurrent pulmonary emboli
4) Left-to-right cardiac shunts
a. Volume overloading pulmonary vasculature
5) Mitral stenosis
a. Backup of blood into pulmonary veins; pulmonary venous hypertension
What are pathologic findings in general in pulmonary hypertension?
1) Atherosclerosis of main elastic pulmonary arteries (PAs)
2) Due to increased pressure on the endothelium leading to injury
3) Proliferation of myointimal cells and smooth muscle cells
Clinically how does pulmonary hypertension present?
1) Exertional dyspnea most common presenting sign
2) Chest pain
3) Chest radiograph shows tapering of the pulmonary arteries
4) Accentuated P2 (sign of PH)
5) Left parasternal heave (sign of right ventricular hypertrophy [RVH])
6) PH imposes an increased afterload on the right ventricle.
7) Right-sided heart failure due to cor pulmonale
How is pulmonary hypertension diagnosed?
1) Catheterization to measure pressures
2) Can also use transthoracic Doppler echocardiogram
Chest x-ray
(1) Enlargement of main pulmonary arteries
a. Rapid tapering of distal vessels
(2) Right ventricular enlargement
How is pulmonary hypertension treated?
1) Diuretics
2) Oxygen
3) Vasodilators
a. Calcium channel blockers, prostanoids, endothelin receptor antagonists
4) Lung transplant
What is cor pulmonale?
Combination of PH and right RVH leading to right-sided heart failure
With good pastures syndrome does renal or pulmonary damage occur first?
Pulmonary hemorrhage with hemoptysis often precedes renal failure
how are restrictive lung diseases characterized?
These disorders are characterized by reduced total lung capacity in the presence of a normal or reduced expiratory flow rate
What are chest wall disorders that cause restrictive lung diseases?
kyphoscoliosis, pleural disease (e.g., mesothelioma), obesity
What are examples of acute or chronic interstitial lung diseases?
Acute interstitial disease (e.g., ARDS)
Chronic interstitial disease
(1) Fibrosing disorders (e.g., pneumoconiosis)
(2) Granulomatous disease (e.g., sarcoidosis)
What is the earliest manifestation of interstitial fibrosis?
1) Earliest manifestation is an alveolitis.
a. Leukocytes release cytokines, which stimulate fibrosis
How are the lungs effected by interstitial fibrosis?
a. Decreases lung compliance
(1) Decreased expansion of the lung parenchyma during inspiration
(2) Damage to type I/II alveolar cells and endothelial cells
b. Functional loss of alveolar and capillary units
1) Increases lung elasticity
2) Recoil of the lung on expiration is increased.
On physical exam what is seen in someone with a restrictive lung disease?
1) Dry cough and exertional dyspnea
2) Late inspiratory crackles in lower lung fields
3) Potential for cor pulmonale
A pulmonary function test would show what in someone with restrictive lung disease?
(1) All volumes and capacities are equally decreased.
(2) Decreased FEV1 sec
(3) Decreased FVC
a. Often the same value as FEV1 sec due to increased lung elasticity
(4) Increased ratio of FEV1 sec/FVC
Example-3/3 = 100% (normal is 80%)
(5) Respiratory alkalosis (arterial Pco2 < 33 mm Hg)
(6) Decreased Pao2
Chest x-ray in a restrictive lung disease patient would show?
Diffuse bilateral reticulonodular infiltrates
How does
Pneumoconioses occur?
1) Inhalation of mineral dust into the lungs leading to interstitial fibrosis
2) Mineral dust includes coal dust, silica, asbestos, and beryllium.
3) Accounts for ∼25% of cases of chronic interstitial lung disease
With pneumoconioses particles 1- to 5-μm that aspirated will lodge where? <0.5 μm lodge where?
1) Reach the bifurcation of the respiratory bronchioles and alveolar ducts
2) Reach the alveoli and are phagocytosed by alveolar macrophages
What is the least and most fibrinogenic molecules?
1) Coal dust is the least fibrogenic particle.
2) Silica, asbestos, and beryllium are very fibrogenic.
Sources of Coal worker's pneumoconiosis include? What is the pigment that accumulates?
1) Coal mines, large urban centers, tobacco smoke
2) (anthracotic pigment)
What are symptoms of Pulmonary anthracosis? What is seen on examination of the lungs?
1) Usually asymptomatic
2) Anthracotic pigment in interstitial tissue and hilar nodes
Note: this occurs in coal workers pneumconiosis
a. Alveolar macrophages with anthracotic pigment are called "dust cells."
What occurs in simple Coal worker's pneumoconiosis?
(1) Fibrotic opacities are smaller than 1 cm in upper lobes and upper portions of lower lobes.
(2) Coal deposits adjacent to respiratory bronchioles produce centriacinar (centrilobular) emphysema
What changes occur in the lungs of someone with complicated Coal worker's pneumoconiosis? Is there increased risk for cancer? What syndrome may occur?
(1) Fibrotic opacities larger than 1 to 2 cm with or without necrotic centers
(2) Crippling lung disease ("black lung" disease)
(3) No increased incidence of TB or primary lung cancer
(4) Cor pulmonale may occur.
(5) Caplan syndrome may occur.
a. CWP plus large cavitating rheumatoid nodules in the lungs
What is the Most common occupational disease in the world? What are sources?
1) silicosis
2) Quartz (crystalline silicone dioxide) is most often implicated.
a. Sources: foundries (casting metal), sandblasting, working in mines
Pathologically what does quartz do in the lungs?
1) Quartz is highly fibrogenic and deposits in the upper lungs.
2) Quartz activates and is cytolytic to alveolar macrophages.
a. Macrophages release cytokines that stimulate fibrogenesis.
On chest x-ray what is seen in both acute and chronic quartz exposure?
1) Acute exposure: Ground glass appearance in all lung fields
2) Chronic exposure:
a. Nodular opacities in the lungs
*Concentric layers of collagen with or without central cavitation
b. "Egg-shell" calcification in hilar nodes
*Rim of dystrophic calcification in the nodes
What are complications of quartz exposure?
(1) Cor pulmonale, Caplan syndrome
(2) Increased risk for developing lung cancer and TB
What are geometric forms of asbestos disease? Where do the asbestos fibers deposit?
(1) Serpentine
a) Curly and flexible fibers (e.g., chrysotile)
b) Produces interstitial fibrosis and lung cancer
(2) Amphibole
a) Straight and rigid (e.g., crocidolite)
b) Produces interstitial fibrosis, lung cancer, mesothelioma
(3) Deposition sites
a) Asbestos fibers deposit in the respiratory unit.
b) Respiratory bronchioles, alveolar ducts, alveoli
Sources of asbestos include what?
(1) Insulation around pipes in old naval ships
(2) Roofing material, ceiling tiles, floor tiles used >20 years ago
(3) Demolition of old buildings
How do asbestos fibers appear in the lungs?
(1) Fibers are coated by iron and protein (called ferruginous bodies)
2) Macrophages phagocytose and coat the fibers with ferritin (synthesized by macrophages)
3) Golden, beaded appearance in sputum or in distal, small airways
What is the most common asbestos induced lung lesion? What are they a precursor of? What type of fibrosis occurs?
(1) Benign pleural plaques
(a) Calcified plaques on the pleura and dome of the diaphragm
(b) They are not a precursor lesion for a mesothelioma.
(2) Diffuse interstitial fibrosis with or without pleural effusions
What is the most common cancer from asbestos-related? After how many years exposure?
1) Primary bronchogenic carcinoma (most common)
(a) Risk further increases if the patient smokes cigarettes.
(b) Occurs ∼20 years after first exposure.
With asbestos exposure what type of cancer develops in the pleura? Describe it?
(4) Malignant mesothelioma of pleura
(a) No etiologic relationship with smoking
(b) Arises from the serosal cells lining the pleura
(c) Encases and locally invades the subpleural lung tissue
(d) Occurs ∼25 to 40 years after first exposure
Is there an increased risk for TB with asbestos? What are complications of asbestos?
1) No increased risk for TB
2) Complications:
Cor pulmonale, Caplan syndrome
where can someone get Berylliosis? Pathologically what occurs? What is there increased risk of?
1) Exposure in the nuclear and aerospace industry
2) Diffuse interstitial fibrosis with noncaseating granulomas
3) Increased risk for cor pulmonale and primary lung cancer
What is the most common noninfectious granulomatous disease of the lungs? Who does it occur more in?
1) sarcoidosis
2) Accounts for ∼25% of cases of chronic interstitial lung disease
3) Common in blacks and nonsmokers
4) More common in women than men
Pathologically what is occurring in sarcoidosis? How is the diagnosis made?
1) Disorder in immune regulation
2) CD4 TH cells interact with an unknown antigen.
3) Releases cytokines causing formation of noncaseating granulomas
4) Diagnosis of exclusion
5) Must rule out other granulomatous diseases
What occurs in the lung of someone with sarcoidosis? What is seen histologically? What is the most common lung symptom?
(1) Granulomas located in the interstitium and mediastinal and hilar nodes
(2) Granulomas contain multinucleated giant cells
(3) Contain laminated calcium concretions (Schaumann bodies) and stellate inclusions (called asteroid bodies)
(4) Dyspnea is the most common symptom.
What happens to the skin in sarcoidosis?
1) Nodular lesions containing granulomas of biopsy
2) Violaceous rash occurs on the nose and cheeks (called lupus pernio).
3) Erythema nodosum:
a. Painful nodules on lower extremities
b. Inflammation of subcutaneous fat
How are the eyes effected in sarcoidosis?
1) produces uveitis
2) Blurry vision, glaucoma, and corneal opacities
What is the most common noninfectious granulomatous disease of the liver?
1) sarcoidosis
2) causes Granulomatous hepatitis
How does sarcoidosis affect the mouth? What endocrine problem occurs? How are the bones affected?
1) Enlarged salivary and lacrimal glands
2) Diabetes insipidus (hypothalamic and posterior pituitary disease)
3) Granulomas in the bone marrow and spleen
What are laboratory findings in someone with sarcoidosis?
1) Increased angiotensin-converting enzyme (ACE; 60%)
a. Nonspecific finding
2) Hypercalcemia (5% of cases)
a. Increased synthesis of 1-α-hydroxylase in granulomas (hypervitaminosis D)
3) Polyclonal gammopathy
4) Cutaneous anergy to common skin antigens (e.g., Candida)
a. Due to consumption of CD4 TH cells in granulomas and loss of cells in alveolar secretions
What is seen on a chest x-ray of someone with sarcoidosis? what is the sign called?
1) Enlarged hilar and mediastinal lymph nodes (called "potato nodes")
2) Reticulonodular densities throughout the lung parenchyma
how is sarcoidosis treated?
1) Majority (75-90%) have spontaneous remission in 2 years and do not require treatment.
2) Corticosteroids if treatment is required
3) Tumor necrosis factor inhibitors
4) Hydroxychloroquine useful if skin involvement is present
What is the prognosis of sarcoidosis?
Approximately 10% to 15% develop severe interstitial fibrosis, leading to cor pulmonale and death.
who does idiopathic pulmonary fibrosis occur in?
1) Accounts for ∼15% of cases of chronic interstitial lung disease
2) More common in males than in females
3) Usually occurs in individuals 40 to 70 years old
pathologically what is occurring in idiopathic pulmonary fibrosis? What appearance does the lung take on?
1) Repeated cycles of alveolitis are triggered by an unknown agent.
2) Release of cytokines produces interstitial fibrosis.
3) Alveolar fibrosis leads to proximal dilation of the small airways.
4) Lung has a honeycomb appearance.
Clinically how does idiopathic pulmonary fibrosis present? What is the treatment? Prognosis?
1) Fever
2) Dyspnea with exertion
3) Chronic, nonproductive cough
4) Late inspiratory crackles
5) Treatment:
None very useful
6) Poor prognosis
An unexplained pleural effusion in a young woman is what until proven otherwise? What does the pleural fluid contain?
1) SLE
2) Pleural fluid contains an inflammatory infiltrate (exudate), and lupus erythematosus cells (neutrophils with phagocytosed DNA) are sometimes present
What is one of the key criteria for diagnosing SLE?
he presence of serositis, pleuritis with a pleural effusion being an example of this type of inflammation.
What are collagen vascular diseases that affect the lungs?
1) Systemic sclerosis
a. Most common cause of death is lung disease.
2) Systemic lupus erythematosus (SLE)
a. Interstitial lung disease occurs in 50% of patients.
b. Pleuritis with pleural effusions
3) Rheumatoid arthritis (RA)
How does RA affect the lungs?
a. Rheumatoid nodules in lungs plus a pneumoconiosis is called Caplan syndrome.
b. Pulmonary findings in RA
(1) Interstitial fibrosis with or without intrapulmonary rheumatoid nodules
(2) Nodules often cavitating
(3) Pleuritis with pleural effusions
What is Extrinsic allergic alveolitis associated with? What are examples? What else is called?
1) exposure to a known inhaled antigen
2) examples:
a. farmers lung = thermophyllic actinomyces
b. mushroom workers disease = thermophyllic actinomyces
c. tobacco workers disease = asperillgius
2) Does not involve IgE antibodies (type I hypersensitivity) or have eosinophilia
4) TH1 mediated hypersensitivity
What is the allergen in farmers lung? What happens on first exposure? Second exposure?
1) Exposure to Saccharopolyspora rectivirgula (thermophilic actinomycetes) in moldy hay
2) First exposure
Patient develops precipitating IgG antibodies (present in serum)
3) Second exposure
a. Antibodies combine with inhaled allergens to form immune complexes. (type III)
b. Immunocomplexes produce an inflammatory reaction in lung tissue.
chronic farmers lung causes what? How is farmers lung treated?
1) Additional component of granulomatous inflammation (type IV hypersensitivity)
2) Treatment
a) Avoidance of antigen with facial mask
b) Corticosteroids
farmers lung is what type of hypersensitivity?
type III and IV
What occurs in Silo fillers disease? What is cause? How is it treated?
1) Inhalation of gases (oxides of nitrogen) from plant material
2) Causes an immediate hypersensitivity reaction associated with dyspnea
3) Treatment: Corticosteroids
Who does byssinosis occur in? What is the allergen?
(1) Occurs in workers in textile factories
(2) Contact with cotton, linen, hemp products
(3) Exposure to bacterial endotoxin from gram-negative bacteria growing on the cotton
What are clinical findings of Byssinosis? When do symptoms improve? When do they return? how is it treated?
(1) Develop dyspnea on exposure to cotton, linen, or hemp products
(2) Workers feel better over the weekend (no exposure to antigens)
(3) Depression occurs when returning to work on Monday ("Monday morning blues")
(4) treat by removing allergen
Hypersensitivity pneumonitis lack an IgE response. What are the diseases?
1) Farmer's lung
2) Silo filler's disease
3) Byssinosis
Which drugs are associated with interstitial fibrosis?
1) Amiodarone
2) Bleomycin and busulfan
3) Cyclophosphamide
4) Methotrexate and methysergide
5) Nitrosourea and nitrofurantoin
when does radiation induced pneumonitis occur? What are clinical findings? What is seen on chest x-ray?
1) Acute pneumonitis may occur 1 to 6 months after therapy.
2) Clinical findings:
Pleural effusions
3) Chest x-ray shows infiltrates
4) Some patients develop chronic radiation pneumonitis.
Histologically how do sarcoid granulomas appear?
ink-staining epithelioid cells and foreign body type of multinucleated giant cells.
What are obstructive lung diseases?
1) emphysema
2) Chronic bronchitis
3) asthma
4) bronchiectasis
What is emphysema?
Permanent enlargement of all or part of the respiratory unit
a. Respiratory bronchioles, alveolar ducts, alveoli
what are causes of emphysema?
(1) Cigarette smoking is the most common cause.
(2) α1-Antitrypsin (AAT) deficiency
What are the Types of emphysema associated with smoking or loss of AAT?
(1) Centriacinar (centrilobular) emphysema
(2) Panacinar emphysema
What happens to compliance and elastance in AAT deficient emphysema? What is the pathologic process?
1) Increased compliance and decreased elasticity
2) Imbalance between elastase and anti-elastases (e.g., AAT)
3) Imbalance between oxidants (free radicals) and antioxidants (e.g., glutathione)
4) Elastase and oxidants derive from neutrophils and macrophages.
5) Net effect of the preceding is destruction of elastic tissue.
How does cigarette smoke lead to emphysema?
1) Cigarette smoke is chemotactic to neutrophils and macrophages.
2) They accumulate in the respiratory unit and release free radicals and elastases.
3) Free radicals in cigarette smoke inactivate AAT and antioxidants.
4) Produces a functional AAT deficiency
What is the normal function of elastic tissue in the lungs? what happens when it is lost?
(1) Fibers attach to the outside wall of the small airways
(2) Fibers apply radial traction to keep the airway lumens open.
3) Destruction of elastic tissue causes loss of radial traction.
a. Small airways collapse, particularly on expiration
Where are the Sites of elastic tissue destruction in emphysema?
(1) Distal terminal bronchiole at its junction with the respiratory bronchiole (RB)
(2) All or part of the respiratory unit
Where are the Sites of obstruction and air trapping in emphysema?
(1) During expiration, the distal terminal bronchioles collapse preventing egress of air out of the respiratory unit.
(2) Trapped air distends parts of the respiratory unit that have lost their elastic tissue support.
What is the Most common type of emphysema in smokers? What occurs pathologically?
1) Centriacinar (centrilobular) emphysema
2) Primarily involves the apical segments of the upper lobes
3) Distal terminal bronchioles and the RBs are the sites of elastic tissue destruction.
4) Air trapped behind the collapsed distal terminal bronchioles distends the RBs.
5) The trapped air increases RV and TLC.
When does panacinar emphysema occur? What are the genetics behind it?
(1) Associated with AAT deficiency
a. Genetic or acquired causes (cigarette smoke inactivates AAT)
(2) Genetic type of AAT deficiency
a. Autosomal dominant
b. MM phenotype is normal.
c. Normal amounts of AAT are synthesized in the liver.
d. Homozygous ZZ type has decreased synthesis of AAT by the liver.
(3) Emphysema develops at an early age in the genetic type.
(4) affects primarily the lower lobes
What is the function of A1AT?
Alpha 1-antitrypsin (A1AT) is produced in the liver, and one of its functions is to protect the lungs from the neutrophil elastase enzyme, which can disrupt connective tissue
Which parts of the lung are primarily affected by panacinar emphysema?
(1) Primarily affects the lower lobes
(2) Distal terminal bronchioles and all parts of the respiratory units are the sites of elastic tissue destruction
(3) Air trapped behind the collapsed terminal bronchioles distends the entire respiratory unit.
When performing a serum protein electrophoesis what is missing in panacinar emphysema?
Absent α1-globulin peak in a serum protein electrophoresis
Clinical findings in centriacinar and panacinar emphysema include what?
1) Progressive dyspnea and hyperventilation
a. Dyspnea is severe and occurs early in the disease.
b. Sometimes patients are called "pink puffers" and blow off CO2
c. Centriacinar type frequently coexists with chronic bronchitis.
2) Breath sounds are diminished due to hyperinflation.
3) Cor pulmonale is uncommon.
Chest x-ray shows what in people with emphysema?
1) Hyperlucent lung fields
2) Increased anteroposterior diameter
3) Vertically oriented heart
4) Depressed diaphragms due to hyperinflated lungs
A pulmonary function in someone with emphysema would show what?
1) Increased TLC due to an increase in RV
2) Decreased FEV1 sec (e.g., 1 L versus 4 L)
3) Decreased FVC (e.g., 3 L versus 5 L)
4) Decreased FEV1 sec/FVC ratio (e.g., 1/3 = 33%)
An arterial blood gas from someone with emphysema would show what?
1) Decreased Pao2 develops late in the disease.
2) Destruction of the capillary bed matches destruction of the respiratory unit.
3) Normal to decreased arterial Pco2 (respiratory alkalosis)
how is emphysema treated?
1) Cessation of smoking most important
2) Pulmonary rehabilitation program
3) Oxygen, using 1 to 2 L/minute, through nasal prongs
4) Maintain O2 saturation of 90%
5) Bronchodilators
a. Catecholamine inhalers/nebulizers
b. Steroid inhalers controversial
c. Anticholinergics
What are Other types of emphysema unrelated to smoking or AAT deficiency?
1) Paraseptal emphysema
2) Irregular emphysema
What occurs in paraseptal emphysema? What is there an increased risk of?
(1) Localized disease in a subpleural location
a. Primarily targets the alveolar ducts and alveoli
(2) Does not produce obstructive airway disease
(3) Increased incidence of spontaneous pneumothorax
a. Due to rupture of subpleural blebs
What is irregular emphysema?
(1) Localized disease is associated with scar tissue.
(2) Does not produce obstructive airway disease
Where is turbulent airflow made into laminar flow in the lungs?
converted to laminar airflow in the terminal (nonrespiratory) bronchioles because of branching
What is small airway disease associated with?
expiratory wheezes due to narrowing of the terminal bronchioles by mucus plugs, inflammation, and fibrosis
What do mucus plugs in the proximal terminal bronchiole cause?
prevent the exodus of a large amount of CO2 arising from the distally located airways producing respiratory acidosis
Criteria for chronic bronchitis include what? What are causes?
1) Productive cough for at least 3 months for 2 consecutive years
2) Causes:
a. Smoking cigarettes (most common)
b. Cystic fibrosis
Pathologically what occurs in chronic bronchitis? Where is the obstruction in comparison to emphysema?
1) Hypersecretion of mucus in bronchi
2) Obstruction to airflow in the terminal bronchioles
3) Airflow obstruction is proximal to the obstruction in emphysema.
Irreversible fibrosis of terminal bronchioles
How do the bronchi change with chronic bronchitis?
(1) Hypersecretion of submucosal mucus-secreting glands in trachea and bronchi
a. Primarily responsible for sputum overproduction
(2) Acute inflammation (neutrophils) often superimposed on chronic inflammation
(3) Loss of ciliated epithelium and presence of squamous metaplasia
How do the terminal bronchioles change in chronic bronchitis?
(1) Mucus plugs in lumens (block the exodus of CO2)
(2) Goblet cell metaplasia
(3) Hypertrophy of mucus-secreting glands
(4) Chronic inflammation and fibrosis narrowing the lumen
What are clinical findings in chronic bronchitis? Is cor pulmonale present? How is heart oriented on x-ray?
1) Productive cough
2) Dyspnea occurs late in the disease.
3) Cyanosis of skin and mucous membranes
4) Decreased O2 saturation from hypoxemia
a. Patients are called "blue bloaters."
5) Tend to be stocky or obese
6) horizontally oriented heart
7) Expiratory wheezing and sibilant rhonchi
8) Cor pulmonale is commonly present.
A chest x-ray would show what in chronic bronchitis?
1) Large, horizontally oriented heart
2) Increased bronchial markings
Pulmonary function tests and arterial blood gases is someone with chronic bronchitis would show what?
1) Less increase in TLC and RV than emphysema
2) Chronic respiratory acidosis
a. Arterial Pco2 > 45 mm Hg
b. Bicarbonate > 30 mEq/L
3) Moderate to severe hypoxemia early in the disease
Why is ozone bad?
It forms highly reactive free radicals in the airways that cause inflammation and irritation, often precipitating asthma.
What is asthma? Where does it occur in lungs? Who does it primarily occur in? What types are there?
1) Episodic and reversible airway disease (most cases)
2) Primarily targets the bronchi and terminal bronchioles
3) Most common chronic respiratory disease in children
a. More common in children than adults
b. Majority (50-80%) develop symptoms before 5 years of age
4) Extrinsic and intrinsic types
Describe the pathologic mechanism of Extrinsic asthma? Which interleukins are involved?
(1) Type I hypersensitivity
a. Typically develops in children with an atopic family history to allergies
(2) Initial sensitization to an inhaled allergen
(a) Stimulate induction of subset 2 helper T cells (CD4 TH2) that release interleukin (IL) 4 and IL-5
(b) IL-4 stimulates isotype switching to IgE production.
(c) IL-5 stimulates production and activation of eosinophils
(3) Inhaled antigens cross-link IgE antibodies on mast cells on mucosal surfaces.
(a) Release of histamine and other preformed mediators
(b) Stimulate bronchoconstriction, mucus production, influx of leukocytes
What is the late phase reaction of extrinsic asthma? When does it occur?
1) Eotaxin is produced.
a. Chemotactic for eosinophils and activates eosinophils
b. Eosinophils release major basic protein and cationic protein.
c. Damage epithelial cells and produce airway constriction
2) occurs 4-8 hours after exposure
Besides the interleukins what other mediators are involved in extrinsic asthma?
(1) LTC-D-E4 causes prolonged bronchoconstriction.
(2) Acetylcholine causes airway muscle contraction
How are the terminal bronchioles altered in extrinsic asthma? What histologic markers are seen?
(1) Formation of spiral-shaped mucus plugs
(a) Contain shed epithelial cells called Curschmann spirals
(b) Pathologic effect of major basic protein and cationic protein
(2) Crystalline granules in eosinophils coalesce to form Charcot-Leyden crystals.
(3) Patchy loss of epithelial cells, goblet cell metaplasia
(4) Thick basement membrane
(5) Smooth muscle cell hypertrophy and hyperplasia
how does extrinsic asthma present clinically?
(1) Episodic expiratory wheezing (inspiratory as well when severe)
(2) Nocturnal cough
(3) Increased anteroposterior diameter
Due to air trapping and increase in residual volume
What is seen on ABG in someone with extrinsic asthma? What can it progress to?
(1) Initially develop respiratory alkalosis
(a) Patients work hard at expelling air through inflamed airways.
(b) May progress into respiratory acidosis if bronchospasm is not relieved
2) Normal pH or respiratory acidosis is an indication for intubation and mechanical ventilation.
3) Eosinophilia, positive skin tests for allergens
how is mild to moderate extrinsic asthma treated? and severe?
1) Treatment of mild disease
a. Metered-dose inhaler with a β2-agonist (e.g., albuterol)
2) Treatment of more advanced disease
a. Metered low-dose inhaler with corticosteroids
b. Use of leukotriene inhibitors (zarfulekast and montelukast)
What are causes of intrinsic asthma?
1) Nonimmune
2) Virus-induced respiratory infection
Examples-rhinovirus, parainfluenza virus, respiratory syncytial virus
3) Air pollutants
O3: free radical; O2 combining with oxides of nitrogen and sulfur
4) Aspirin or nonsteroidal drug sensitivity
(4) Stress, exercise, cigarette smoke
What is bronchiectasis?
1) Permanent dilation of the bronchi and bronchioles
a. Due to destruction of cartilage and elastic tissue by chronic necrotizing infections
What are causes of
Bronchiectasis? Most common in US and most common in world?
(1) Cystic fibrosis (CF)
a. Most common cause in the United States
(2) Infections
(a) TB is the most common cause worldwide.
(b) Adenovirus, Staphylococcus aureus, Haemophilus influenzae
(3) Bronchial obstruction
Example-proximally located bronchogenic carcinoma occludes the lumen.
(4) Primary ciliary dyskinesia
(a) Absent dynein arm in cilia
(b) Dynein arm contains ATPase (adenosine triphosphatase) for movement of the cilia.
(5) Allergic bronchopulmonary aspergillosis
Which lobes are most commonly affected by bronchiectasis? What happens to the lobes?
1) Most commonly occurs in the lower lobes
2) Dilated bronchi and bronchioles are filled with pus
a. Dilated airways extend to the lung periphery.
b. Dilations are tubelike and/or saccular.
Clinically what is found in someone with bronchiectasis?
1) Cough productive of copious sputum (bronchorrhea)
2) Hemoptysis that is sometimes massive
3) Digital clubbing
4) Cor pulmonale
What will a chest x-ray show in someone with bronchiectasis?
Crowded bronchial markings extend to the lung periphery.
What type of genetic mutation occurs in cystic fibrosis? Who is primarily affected? What is the median age of diagnosis and survival time?
(1) Autosomal recessive disease CFTR gene on chromosome 7
(2) Primarily affects whites (>98%)
a. Uncommon in Asians and blacks
(3) Median age of diagnosis ∼5 months
(4) Median survival age: 30 years
What is the Most common fatal hereditary disorder of whites in United States?
Which chromosome is affected in CF? What is the mutation?
(1) Three nucleotide deletion on chromosome 7
a. Nucleotides normally code for phenylalanine
What is defective in CF? What happens to this protein during processing?
1) Production of a defective CF transmembrane conductance regulator (CFTR) for chloride ions
2) CFTR Cl- is degraded in the Golgi apparatus.
a. Due to defective protein folding
What is the effect of not having a functional CFTR? What organs are particularly affected?
1) Loss of CFTR Cl- causes decreased Na+ and Cl- reabsorption in sweat glands.
a. Basis of the sweat test
2) Effect of loss of CFTR Cl- in other secretions
a. Increased Na+ and water reabsorption from luminal secretions
b. Decreased Cl- secretion out of epithelial cells into luminal secretions
c. Net effect is dehydration of body secretions due to lack of NaCl
d. Secretions are dehydrated in bronchioles, pancreatic ducts, bile ducts, meconium, and seminal fluid.
How is the respiratory and cooling system of the body affected by CF? What organisms commonly infect CF patients?
(1) Nasal polyps (25% of cases)
(2) Heat exhaustion
a. Loss of sodium-containing fluid from skin
(3) Respiratory infections/failure
(a) Pseudomonas aeruginosa is the most common respiratory pathogen.
(b)Other common pathogens-S. aureus, H. influenzae
(4) Cor pulmonale commonly occurs.
(5) Pneumothorax (20%)
a. Rupture of blebs that develop from infection
How is the digestive system affected by CF? What condition develops secondary to digestive problems?
1) Malabsorption (80%)
(a) Pancreatic exocrine deficiency
(b) Atrophy of glands from dehydrated secretions blocking the lumens
(c) Chronic pancreatitis
(2) Type 1 diabetes mellitus (20%)
a. Due to chronic pancreatitis
(3) Gallstones (>50%)
(a) Usually in older CF patients
(b) Stasis of thickened bile
(c) Common bile duct obstruction (15-20%)
(4) Secondary biliary cirrhosis
a. Due to obstruction of bile ductules by thick secretions
Is male or female fertility more affected by CF?
1) Infertility in males (95%)
a. Atresia of vas deferens
2) Infertility in females (20%)
What are signs of CF in infants?
1) Meconium ileus (20%)
a. Small bowel obstruction in newborn
2) Rectal prolapse
a. Straining at stool
How are newborns screed for CF?
Increased serum immunoreactive trypsin levels
What are sweat values in adults and children that have CF?
(1) Sweat chloride > 60 mmol/L in children
(2) Sweat chloride > 80 mmol/L in adult
How is CF treated? What type of vitamins need to be given?
(1) Antibiotics for documented respiratory infections
(2) Bronchodilators
(3) Pancreatic enzyme replacement
(4) Corticosteroids in children (alternate day)
(5) Vitamin supplements
a. Fat-soluble vitamins important
(6) Recombinant human deoxyribonuclease aerosol
b. Improves mucociliary clearance of viscid sputum
How is Centriacinar (centrilobular) emphysema is characterized histologically? What is destroyed?
1) by trapping of air in the respiratory bronchioles. The elastic fibers of the distal TB are destroyed, causing obstruction to airflow. This causes the trapped air to distend the RBs, whose elastic tissue support is destroyed.
How is Panacinar emphysema characterized?
by trapping of air in the entire respiratory unit behind the collapsed TB.
In emphysema how are the following labs affected:
1) Pao2?
2) Paco2?
3) pH?
4) Cyanosis?
5) Habitus?
6) Cor pulmonale?
7) Onset of hypoxemia?
8) Onset of dyspnea?
1) Decreased
2) Normal to decreased
3) Normal to increased
4) Absent
5) Thin
6) Rare
7) Late
8) Early
In chronic bronchitis how are the following labs affected:
1) Pao2?
2) Paco2?
3) pH?
4) Cyanosis?
5) Habitus?
6) Cor pulmonale?
7) Onset of hypoxemia?
8) Onset of dyspnea?
1) Decreased
2) Increased
3) Decreased
4) Present
5) Stocky
6) Common
7) Early
8) Late
What is the most common fatal cancer in both men and women? How is the incidence changing and what is the peak incidence?
1) lung cancer
2) Incidence of lung cancer is declining in men but increasing in women.
3) Peak incidence is at 55 to 65 years of age.
What are causes of lung cancer?
1. Cigarette smoking most common cause
* Risk increases with quantity and duration of smoking
2. Radon gas (uranium mining)
3. Asbestos
4. Certain metals
a. Chromium, cadmium, beryllium, arsenic
5. Secondhand smoke
6. Ionizing radiation
7. Air pollution
8. History of tuberculosis
how are lung cancers classified?
Classified as small cell (13%) or non-small cell (87%) cancers
List the Primary lung cancers by specific type in decreasing incidence?
1) Adenocarcinoma
2) Squamous cell carcinoma
3) Small cell lung carcinoma
4) Large cell carcinoma
5) Bronchial carcinoid
What do Squamous and small cell lung carcinomas have in common?
1) Greatest smoking association
2) Tend to be centrally located (i.e., main stem bronchus)
Where do adenocarcinomas occur? What is there link to smoking?
1. Weakest smoking association
2. Tend to be more peripherally located
a. Filters in cigarettes remove large carcinogens leaving small ones to move peripherally.
Where are common sites of primary lung cancer metastisis?
1. Hilar lymph nodes most common site
2. Adrenal gland (50%)
3. Liver (30%)
4. Brain (20%)
5. Bone (osteolytic)
What is the term applied to a peripheral lung nodule < 5 cm? What are causes in decreasing order of frequency?
1) A solitary pulmonary nodule or coin lesion
2) granulomas (e.g., TB, histoplasmosis), malignancy (usually primary cancer), and a bronchial (chondroid) hamartoma
How often are solitary nodules in the lung malignant in someone less than 35? over 50?
Patients < 35 years old have a 1% risk of a solitary coin lesion representing a malignancy, but patients ≥ 50 years old have a 50% to 60% risk of malignancy, usually a primary cancer
What is the most common lung cancer? Why? What is the most common symptom?
1) extrapulmonary metastisis
a. Primary breast cancer most common cause
b. Colon cancer, renal cell carcinoma
2) Dyspnea is the most common symptom.
What are general clinical findings in primary lung cancer?
1) Cough is most common symptom (75%)
2) Weight loss (40%)
3) Chest pain (30%)
4) Hemoptysis (25-30%)
5) Dyspnea
How does a pancoast tumor present? What type of cancer is it and where is it located?
1. Usually a primary squamous cancer located at the extreme apex of lung
2. Destruction of superior cervical sympathetic ganglion produces Horner syndrome:
(1) Ipsilateral lid lag
(2) Miosis (pinpoint pupil)
(3) Ipsilateral anhydrosis (lack of sweating)
What are paraneoplastic syndrome findings that occur in primary lung cancer?
1)Digital clubbing
2) Muscle weakness (Eaton-Lambert syndrome)
a. Antibody directed against calcium channel in muscle
b. Usually associated with small cell carcinoma
2) Ectopic hormone secretion
a. ADH and ACT = small cell
b. PTH related protein = squamous cell
If a central mass is seen on chest x-ray what is differential? If peripheral?
1. Central masses
a) Squamous cell carcinoma
b) Small cell carcinoma
2. Peripheral masses
a) Adenocarcinoma
c) Scar carcinoma
Aside from chest x-ray what are other tests used to diagnose lung cancer?
1) Sputum cytologic examination
2) Fine needle aspiration
3) Bronchoscopy with lavage
4) New techniques for early detection
a. Low-dose spiral (helical) CT scan
b. Molecular markers in sputum
What are treatments for lung cancer?
1. Surgery
2. Radiation
3. Chemotherapy
4. Targeted biologic therapies
* Bevacizumab--blocks VEGF-A and erlotinib--blocks EGFR
What is erlotinib used for? What does it do?
1) treat non-small cell lung cancer, pancreatic cancer and several other types of cancer
2) blocks tyrosine kinase EGFR
What is bevacizumab used for? What does it do?
1) metastatic colon cancer and non-small cell lung cancer
2) prevents angiogenesis by blocking VEGF-A
Do non-small cell or small cell lung cancers have a better prognosis?
1. Non-small cell cancers fare better than small cell carcinoma.
2. Overall combined 5-year survival rate is ∼15%.
Who is adenocarcinoma more common in? What are the different types and characterisitics of each?
1) More common in women
2) Some types are associated with cigarette smoking
3) Scar carcinomas: develop in scars (e.g., old tuberculous granuloma); no relationship to smoking
4) Bronchioloalveolar carcinoma: derives from Clara cells (nonciliated epithelium); malignant cells spread along alveolar walls (look like pegs); radiologically mimic lobar pneumonia; no relationship to smoking
Who is squamous cell carcinoma more common in? What is it associated with? What will the tumor tend to do? What can it secrete?
1) More common in men
2) Strong association with cigarette smoking
3) Tend to cavitate
4) May ectopically secrete PTH-related protein (peptide)
Who is small cell carcinoma more common in? What is it associated with? What cells does it arise from? Does it grow rapid or slow? What may it secrete?
1) More common in men
2) Strong association with cigarette smoking
3) Arise from neuroendocrine cells (Kulchitsky cells)
4) Rapidly growing cancer that metastasizes early
5) May ectopically secrete ADH or ACTH
where does large cell carcinoma occur? What are it characteristics?
1) peripheral
2) Undifferentiated cancer that metastasizes early; no relationship to smoking
3) highly anaplastic
where is bronchial carcinoma located? What cells does it arise from? What is the mean age? Does it metastisize? How does it present?
1) central
2) Low-grade cancer of neuroendocrine origin; no association with smoking;
3) present at a mean age of 55 years old; most common primary lung tumor in children;
4) ∼ 20% locally metastasize
5) present with hemoptysis (most common), cough, carcinoid syndrome (<1%)
What is carcinoid syndrome? What does it occur with?
1) The syndrome includes flushing and diarrhea, and, less frequently, heart failure and bronchoconstriction.
2) It is caused by endogenous secretion of mainly serotonin and kallikrein.
3) associated with bronchial carcinoma
When a tumor metastisizes to the lung where in the lung does it go?
1) More common than primary cancer
2) Sites of metastasis: parenchyma (most common), pleura/pleural space, endobronchial mucosa, lymphatics (causes dyspnea)
Where do bronchial hamaratomas occur? What type of proliferation is present? What is seen on chest x-ray?
1) Peripheral (90%) Central (10%)
2) Non-neoplastic proliferation of cartilage and adipose tissue
3) Appears as solitary "coin" lesion on chest radiograph; popcorn calcifications
A sputum analysis shows orange-staining, keratinized cells with irregular, hyperchromatic nuclei. What cancer is present?
squamous cell carcinoma
What is the difference between an anterior mediastinal mass in older and younger patients?
1) Usually metastatic primary lung cancer in older patients
2) Usually primary disease in younger patients
3) Anterior mediastinum is the most common site (>50%)
What are the most common mediastinal masses in decreasing order?
(1) Neurogenic tumors
(2) Thymomas
(3) Pericardial cyst
(4) Malignant lymphomas
(5) Teratoma
where are neurogenic tumors located in the mediastinum? What type of tumor is it if it occurs in children? In adults?
(a) Located in the posterior mediastinum
(b) Usually malignant in children
* Neuroblastoma
(c) Usually benign in adults
* Ganglioneuroma
Where is a pericardial cyst located? Where do malignant lymphomas present? What is it if in a woman?
1) Located in the middle mediastinum
2)a. Located in the anterior mediastinum
b. Usually nodular sclerosing Hodgkin's lymphoma in a woman
Where are teratomas located? Are they benign or malignant?
(a) Located in the anterior mediastinum
(b) Majority are benign cystic teratomas.
(c) Small percentage are malignant teratomas
Where do thymomas occur? Are they benign or malignant? is lymphoid or epithelium neoplastic?
(1) Located in the anterior mediastinum
(2) Benign (70%), malignant (30%)
(3) Epithelium, not lymphoid tissue, is the neoplastic component.
Which diseases are associated with thymomas?
1) Majority express systemic symptoms of myasthenia gravis
a. Less than 15% of myasthenia patients have a thymoma.
2) Majority (65-75%) have follicular B cell hyperplasia in the thymus.
a. Site for synthesis of antiacetylcholine receptor antibodies
3) Hypogammaglobulinemia
4) Pure RBC aplasia
5) Increased incidence of autoimmune disease (e.g. Graves' disease)
How does pleural fluid move? What is movement dependent on?
1) Fluid moves from parietal pleura to pleural space to lungs.
2) Movement depends upon the balance of Starling pressures
a. Parietal capillary hydrostatic pressure > visceral capillary hydrostatic pressure.
b. Parietal capillary oncotic pressure equals visceral capillary hydrostatic pressure
What are causes of plueral effusions?
1. Increased hydrostatic pressure in visceral pleura
a. Example-congestive heart failure
2. Decreased oncotic pressure
a. Example-nephrotic syndrome
3. Obstruction of lymphatic drainage from the visceral pleura
a. Example-lung cancer
4. Increased vessel permeability of visceral pleural capillaries
a. Examples-pulmonary infarction, pneumonia
5. Metastasis to the pleura
a. Example-metastatic breast cancer
What are the types of pleural effusions?
1) Transudates
2) Exudates
3) Chylous
4) Pseudochylous
What does transudate causing pleural effusion mean? What are causes?
1. Ultrafiltrate of plasma involving disturbances in Starling pressures
2.a) Increased hydrostatic pressure in congestive heart failure most common overall cause of effusion
b) Decreased oncotic pressure in nephrotic syndrome
What does exudate causing pleural effusion mean? What are causes?
1. Protein-rich and cell-rich fluid
a. Due to an increased vessel permeability in acute inflammation
2. Examples-pneumonia, tuberculosis, infarction, metastasis
What does chylous exudate causing pleural effusion mean? What are causes? How is it diagnosed?
1) Indicates interruption of the thoracic duct
2) Malignancy (most common)
a. Blocks lymphatic drainage
3) Trauma
a. Iatrogenic tear during surgery or pathologic
4) Turbid, milky appearance
a. Due to chylomicrons (diet-derived triglyceride)
b. Chylomicrons form a supranate in a test tube after refrigeration.
5) PF triglyceride > 110 mg/dL is diagnostic
What does psuedochylous exudate causing effusion mean? What are causes? How is it diagnosed?
1) Turbid, milky appearance
2) Caused by inflammation with increased amount of necrotic debris
a. PF has increased cholesterol
3) Most commonly caused by rheumatoid lung disease
What tests are useful for distinguishing transudate vs exudate? How does the pH vary between the two?
1) PF and serum concentrations of lactate dehydrogenase (LDH) and protein are most useful.
a. Ratios of PF protein and LDH to serum protein and LDH increase test sensitivity and specificity.
b. Test sensitivity is 99% and specificity is 98% if at least one of the three criteria for an exudate is present.
2) Additional criteria
a. pH > 7.4 indicates a transudate.
b. pH < 7.4 indicates an exudate
Clinically what is seen with a pleural effusion?
1) Dullness to percussion
2) Absent breath sounds
3) Absent vocal tactile fremitus
4) Contralateral shift of the mediastinum
a. Only large effusions
Chest x-ray of a pleural effusion would show what?
1. Blunting of the costophrenic angle
2. Obscuration of the diaphragm
Who does spontaneous pneumothorax occur in? Who is at increased risk?
1. More common in men than women
2. Commonly seen in tall, thin, young men 20 to 40 years of age
3. Risk increases with smoking
4. Approximately 25% recurrence rate within 2 years
What are causes of a spontaneous pneumothorax?
1) Primary (idiopathic; most common)
2) Chronic obstructive lung disease
3) Marfan syndrome
4) Scuba diving
5) Insertion of subclavian catheter
why do the ventricular muscle cells contain invagination of surface membranes ( transverse tubules) and how is this different from skeletal muscles
transverse tubules allow deep access of interstial fluid into the cardiac muscle fiber. The cardiac muscle t-tubules has a larger diameter and is filled with glycocalyx (which is full of negative charges, there4 can hold Ca2+ close for when need it for Ca2+ triggered-Ca2+ release)
The most common secondary cause of spontaneous pneumothorax is?
Paraseptal emphysema
Pathologically what occurs in a spontaneous pneumothorax? What is lost?
1. Rupture of a subpleural or intrapleural bleb produces a hole in the pleura.
2. Pleural cavity pressure is the same as the atmospheric pressure.
3. Loss of the negative intrathoracic pressure
4. Causes a portion of lung or the entire lung to collapse
clinically how will someone with a spontaneous pneumothorax present?
1. Sudden onset of dyspnea with pleuritic type of chest pain (90%)
2. Physical examination
a. Tympanitic percussion note
b. Absent breath sounds
c. Trachea deviated to the side of the collapse if there is total lung collapse
What does a chest x-ray show in someone with spontaneous pneumothorax?
1. White visceral pleural line
2. Absence of vessel markings peripheral to line
3. elevated diaphragm ipsalaterally
4. tracheal shift ispsalaterally
How is a spontaneous pneumothorax treated?
1) Observation alone if asymptomatic and pneumothorax < 15%
2) One hundred percent oxygen administration
a. Reduces partial pressure of nitrogen; hence, increasing rate of pneumothorax absorption
3) Chest tube insertion or thoracoscopy may be required
What causes tension pneumothorax?
penetrating trauma to lungs; check valve type of pleural tear
Pathologically what is occurring in a tension pneumothorax?
1) Flap-like pleural tear (check valve) allows air into the pleural cavity but prevents its exit.
a. Similar in concept to filling a tire up with air
2) Increased pleural cavity pressure with each breath
3) Produces compression atelectasis
Clinically and on physical exam what is seen in someone with tension pneumothorax?
1) Sudden onset of severe dyspnea and pleuritic chest pain
2) Physical examination
a. Tympanitic percussion note and absent breath sounds
b. Trachea and mediastinal structures deviate to contralateral side if large tension pneumothorax
3) Compromised venous return to the heart, if the pneumothorax is located on the left side
How is a tension pneumothorax treated?
(1) Relieve pressure first.
a. Insert a needle into the second intercostal space on the midclavicular line.
(2) Insert a chest tube.
What are the following values for a pleural transudate?
PF protein/serum protein
PF LDH/serum LDH
1) <0.5
2) <0.6
3) <200 U/L
What are the pleural fluid values for an exudate?
PF protein/serum protein
PF LDH/serum LDH
1) >0.5
2) >0.6
3) >200 U/L