16 Upper and Lower Respiratory Disorders

Signs and Symptoms of Respiratory Disease

Table 16-1. Common Symptoms of Respiratory Disease
SymptomCauses and Discussion
Dyspnea Difficulty with breathing
Due to stimulation of J receptors causing decrease in full inspiration
Causes of dyspnea
Decreased compliance (e.g., interstitial fibrosis)
Increased airway resistance (e.g., chronic bronchitis)
Chest bellows disease (e.g., obesity, kyphoscoliosis)
Interstitial inflammation/fluid accumulation (e.g., leftsided heart failure)
Cough Cough with a normal chest !ray
"ostnasal discharge is the most common cause
#octurnal cough
$%&D' due to acid reflu! in tracheobronchial tree at night
(ronchial asthma' due to bronchoconstriction
"roducti)e cough
Chronic bronchitis' due to smoking cigarettes
*ypical bacterial pneumonia
(ronchiectasis
Drugs causing cough
+C% inhibitors' inhibit degradation of bradykinin, causing mucosal swelling and irritation in
tracheobronchial tree
+spirin' causes an increase in ,* CD%- (bronchoconstrictors)
.emoptysis Coughing up bloodtinged sputum
/echanisms
"arenchymal necrosis
(ronchial and/or pulmonary )essel damage
Causes
Chronic bronchitis (most common cause)
"neumonia, bronchogenic carcinoma
*(, bronchiectasis, aspergilloma (fungus li)ing in a ca)itary lesion)
+C%, angiotensincon)erting en0yme1 $%&D, gastroesophageal reflu! disease1 ,*, leukotriene1 *(, tuberculosis.
Signs and Symptoms of Respiratory Disease
Table 16-1. Common Symptoms of Respiratory Disease
SymptomCauses and Discussion
Dyspnea Difficulty with breathing
Due to stimulation of J receptors causing decrease in full inspiration
Causes of dyspnea
Decreased compliance (e.g., interstitial fibrosis)
Increased airway resistance (e.g., chronic bronchitis)
Chest bellows disease (e.g., obesity, kyphoscoliosis)
Interstitial inflammation/fluid accumulation (e.g., leftsided heart failure)
Cough Cough with a normal chest !ray
"ostnasal discharge is the most common cause
#octurnal cough
$%&D' due to acid reflu! in tracheobronchial tree at night
(ronchial asthma' due to bronchoconstriction
"roducti)e cough
Chronic bronchitis' due to smoking cigarettes
*ypical bacterial pneumonia
(ronchiectasis
Drugs causing cough
+C% inhibitors' inhibit degradation of bradykinin, causing mucosal swelling and irritation in
tracheobronchial tree
+spirin' causes an increase in ,* CD%- (bronchoconstrictors)
.emoptysis Coughing up bloodtinged sputum
/echanisms
"arenchymal necrosis
(ronchial and/or pulmonary )essel damage
Causes
Chronic bronchitis (most common cause)
"neumonia, bronchogenic carcinoma
*(, bronchiectasis, aspergilloma (fungus li)ing in a ca)itary lesion)
+C%, angiotensincon)erting en0yme1 $%&D, gastroesophageal reflu! disease1 ,*, leukotriene1 *(, tuberculosis.
ulmonary !unction Tests
Calculation of the al)eolararterial (+a) gradient
page 234
page 235
Calculate the +a gradient in a patient breathing 6.76 82 who has a "C82 of 36 mm
.g and "a82 of -6 mm .g. "+82 9 6.76 (:;7) 36/6.3 9 ;;- mm .g. +a gradient 9
;;- -6 9 :- mm .g, which is medically significant and indicates one or more of the
abo)ementioned lung disorders or a righttoleft shunt in the heart.
page 235
page 23:
;. +a gradient is the difference between the al)eolar "82 ("+82) and arterial "82 ("a82).
a. +a gradient is normally due to a mismatch between )entilation and perfusion in the
lungs.
%!ample+n +a gradient e!ists when perfusion is greater than )entilation in the
lower lobes.
b. It is useful in differentiating causes of hypo!emia (decreased "a82).
ii .ypo!emia due to pulmonary causes increases +a gradient.
iii .ypo!emia due to e!trapulmonary causes has a normal +a gradient.
2. Calculation of the +a gradient
a. "+82 9 < 82 (:;7) arterial "C82/6.3
< 82 is the percentage of 82 the patient is breathing1 :;7 is the atmospheric
pressure (:56 mm .g) minus the water )apor pressure (-: mm .g)1 and 6.3 is
the respiratory =uotient.
b. %!ample using normal )alues
ii #ormal "+82 9 6.2; (:;7) -6/6.3 9 ;66 mm .g
iii #ormal "a82 9 >4 mm .g
iiii #ormal +a gradient 9 ;66 mm .g >4 mm .g 9 4 mm .g
ivi /edically significant +a gradient 76 mm .g
2. Causes of hypo!emia with an increased +a gradient
a. ?entilation defect
ii Impaired 82 deli)ery to the al)eoli for gas e!change
iii %!ampleairway collapse due to the respiratory distress syndrome
b. "erfusion defect
ii Decreased or absent blood flow to the al)eoli
iii %!amplepulmonary embolus
c. Diffusion defect
ii 82 cannot diffuse through the al)eolarcapillary interface.
iii %!ampleinterstitial fibrosis, pulmonary edema
d. &ighttoleft cardiac shunt
%!ampletetralogy of @allot
ii Causes of hypo!emia with a normal +a gradient
a. Depression of the respiratory center in the medulla
%!amplesbarbiturates, brain inAury
b. Bpper airway obstruction
ii CafC coronary (food blocking airway)
iii %piglottitis due to Hemophilus influenzae
iiii Croup due to parainfluen0a )irus (narrows the trachea)
e. Chest bellows (muscles of respiration) dysfunction
ii "araly0ed diaphragm
iii +myotrophic lateral sclerosis with degeneration of anterior horn cells
Calculate the +a gradient in a patient breathing room air who has a "C82 of 36 mm
.g and "a82 of -6 mm .g. "+82 9 6.2; (:;7) 36/6.3 9 46 mm .g. +a gradient 9
46 -6 9 ;6 mm .g, which is not medically significant and indicates an
e!trapulmonary cause of hypo!emia.
Calculation of the al)eolararterial (+a) gradient
page 234
page 235
Calculate the +a gradient in a patient breathing 6.76 82 who has a "C82 of 36 mm
.g and "a82 of -6 mm .g. "+82 9 6.76 (:;7) 36/6.3 9 ;;- mm .g. +a gradient 9
;;- -6 9 :- mm .g, which is medically significant and indicates one or more of the
abo)ementioned lung disorders or a righttoleft shunt in the heart.
page 235
page 23:
;. +a gradient is the difference between the al)eolar "82 ("+82) and arterial "82 ("a82).
a. +a gradient is normally due to a mismatch between )entilation and perfusion in the
lungs.
%!ample+n +a gradient e!ists when perfusion is greater than )entilation in the
lower lobes.
b. It is useful in differentiating causes of hypo!emia (decreased "a82).
ii .ypo!emia due to pulmonary causes increases +a gradient.
iii .ypo!emia due to e!trapulmonary causes has a normal +a gradient.
2. Calculation of the +a gradient
a. "+82 9 < 82 (:;7) arterial "C82/6.3
< 82 is the percentage of 82 the patient is breathing1 :;7 is the atmospheric
pressure (:56 mm .g) minus the water )apor pressure (-: mm .g)1 and 6.3 is
the respiratory =uotient.
b. %!ample using normal )alues
ii #ormal "+82 9 6.2; (:;7) -6/6.3 9 ;66 mm .g
iii #ormal "a82 9 >4 mm .g
iiii #ormal +a gradient 9 ;66 mm .g >4 mm .g 9 4 mm .g
ivi /edically significant +a gradient 76 mm .g
2. Causes of hypo!emia with an increased +a gradient
a. ?entilation defect
ii Impaired 82 deli)ery to the al)eoli for gas e!change
iii %!ampleairway collapse due to the respiratory distress syndrome
b. "erfusion defect
ii Decreased or absent blood flow to the al)eoli
iii %!amplepulmonary embolus
c. Diffusion defect
ii 82 cannot diffuse through the al)eolarcapillary interface.
iii %!ampleinterstitial fibrosis, pulmonary edema
d. &ighttoleft cardiac shunt
%!ampletetralogy of @allot
ii Causes of hypo!emia with a normal +a gradient
a. Depression of the respiratory center in the medulla
%!amplesbarbiturates, brain inAury
b. Bpper airway obstruction
ii CafC coronary (food blocking airway)
iii %piglottitis due to Hemophilus influenzae
iiii Croup due to parainfluen0a )irus (narrows the trachea)
e. Chest bellows (muscles of respiration) dysfunction
ii "araly0ed diaphragm
iii +myotrophic lateral sclerosis with degeneration of anterior horn cells
Calculate the +a gradient in a patient breathing room air who has a "C82 of 36 mm
.g and "a82 of -6 mm .g. "+82 9 6.2; (:;7) 36/6.3 9 46 mm .g. +a gradient 9
46 -6 9 ;6 mm .g, which is not medically significant and indicates an
e!trapulmonary cause of hypo!emia.
Dpirometry
page 233
Bseful in distinguishing restricti)e from obstructi)e lung disease
;. ?olumes and capacities that are not directly measured by spirometry
a. @unctional residual capacity (@&C)
*otal amount of air in the lungs at the end of a normal e!piration
b. *otal lung capacity (*,C)
*otal amount of air in a fully e!panded lung
c. &esidual )olume (&?)
?olume of air left o)er in the lung after ma!imal e!piration
2. *idal )olume (*?)
o ?olume of air that enters or lea)es the lungs during normal =uiet respiration
2. @orced )ital capacity (@?C), forced e!piratory )olume in ; second (@%?;sec), and @%?;sec/@?C
a. @?C is the total amount of air e!pelled after a ma!imal inspiration
#ormal @?C is 4,
b. @orced e!piratory )olume in ; second (@%?;sec)
ii +mount of air e!pelled from the lungs in ; second after a ma!imal inspiration
iii #ormal @%?;sec is -,
b. &atio of @%?;sec/@?C is normally 36<.
#ormal ratio is -,/4,, or 36<.
2. %!piratory reser)e )olume (%&?)
ii It refers to the amount of air forcibly e!pelled at the end of a normal e!piration.
ii It is commonly used to calculate residual )olume (@&C %&? 9 &?).
7. Comparison of pulmonary function tests in restricti)e and obstructi)e lung disease
Table 16-". Comparison of ulmonary !unction Tests in Restricti#e and $bstructi#e
Lung Disease
arameter Restricti#e Disease $bstructi#e Disease
*otal lung capacity Decreased Increased
&esidual )olume Decreased Increased
@%?;sec Decreased Decreased
@?C Decreased Decreased
@%?;sec/@?C #ormal to increased Decreased
"a82 Decreased Decreased
+a gradient Increased Increased
+a, al)eolararterial1 @%?, forced e!piratory )olume1 @?C, forced )ital capacity.
Upper %irway Disorders
Choanal atresia
;. Bnilateral or bilateral bony septum between the nose and the pharyn!
2. #ewborn turns cyanotic when breastfeeding.
o Crying causes the child to Epink upE again.
Choanal atresia
;. Bnilateral or bilateral bony septum between the nose and the pharyn!
2. #ewborn turns cyanotic when breastfeeding.
o Crying causes the child to Epink upE again.
#asal polyps
;. #asal polyps are nonneoplastic tumefactions.
o De)elop as a response to chronic inflammation
2. +llergic polyps
a. /ost common polyp
b. /ost often seen in adults with a history of Ig%mediated allergies
2. #asal polyps associated with aspirin and other nonsteroidal drugs
a. %pidemiology
/ost often occur in women with chronic pain syndromes
b. "athogenesis
ii Drugs block cycloo!ygenase lea)ing the lipo!ygenase pathway open.
iii ,eukotrienes (,*) CD%- are increased, causing bronchoconstriction.
b. Clinical triadnonsteroidal drugs, asthma, and nasal polyps
2. #asal polyps are often associated with cystic fibrosis.
8bstructi)e sleep apnea (8D+)
;. %pidemiology
a. %!cessi)e snoring with inter)als of breath cessation (called apnea)
b. Causes
i. 8besity ()ery common)
"haryngeal muscles collapse due to the weight of tissue in the neck.
ii. *onsillar hypertrophy, nasal septum de)iation
2. "athogenesis
o +irway obstruction causes C82 retention, leading to hypo!emia.
2. Clinical findings
a. %!cessi)e snoring with episodes of apnea
b. Daytime somnolence often simulating narcolepsy
7. ,aboratory findings
c. Decreased "82 and 82 saturation during apneic episodes
d. Increase in arterial "C82 (respiratory acidosis)
-. Complications
e. "ulmonary hypertension (".) leading to right )entricular hypertrophy
Called cor pulmonale (see section ?II)
ii Decondary polycythemia
Due to a hypo!emic stimulus for erythropoietin release
2. "olysomnography
o Confirmatory test that documents periods of apnea during sleep
2. *reatment
o #asal continuous positi)e airway pressure (C"+")
o Durgical correction of any obstructi)e lesions, weight loss
Dinusitis
;. %pidemiology
a. /a!illary sinus is most often in)ol)ed in adults.
b. %thmoid sinus is most often in)ol)ed in children.
c. Causes
i. Bpper respiratory infections (e.g., )irus, bacteria)
ii. De)iated nasal septum, allergic rhinitis, barotrauma, smoking cigarettes
d. "athogens causing sinusitis
i. Streptococcus pneumoniae (most common)
ii. &hino)iruses, anaerobes (chronic sinusitis)
iii. Dystemic fungi (e.g., Mucor or Aspergillus species)
Diabetics commonly ha)e sinusitis due to Mucor species.
2. "athogenesis
o (lockage of drainage into the nasal ca)ity
2. Clinical findings
a. @e)er, nasal congestion, pain o)er sinuses
b. Computed tomography (C*) scan is the most sensiti)e test.
#asopharyngeal carcinoma
page 23>
page 2>6
;. %pidemiology
a. /ost common malignant tumor of the nasopharyn!
b. /ale dominant
c. Increased incidence in the Chinese and +frican populations
2. "athogenesis
o Causal relationship with %pstein(arr )irus (%(?)
2. "athologic findings
a. D=uamous cell carcinoma or undifferentiated cancer
b. /etastasi0es to cer)ical lymph nodes
,aryngeal carcinoma
;. %pidemiology and pathogenesis
a. /ore common in men than in women
b. &isk factors
i. Cigarette smoking (most common cause)
ii. +lcohol (synergistic effect with smoking)
iii. D=uamous papillomas and papillomatosis
.uman papilloma)irus type 5 and ;; association
c. /aAority are located on the true )ocal cords
2. /aAority are keratini0ing s=uamous cell carcinomas.
7. Clinical findings
o "ersistent hoarseness often associated with cer)ical lymphadenopathy
%telectasis
,oss of lung )olume due to inade=uate e!pansion of the airspaces (collapse)
&esorption atelectasis
page 2>6
page 2>;
;. "athogenesis
a. +irway obstruction pre)ents air from reaching the al)eoli.
8bstruction occurs in bronchi, segmental bronchi, or terminal bronchioles.
b. Causes of obstruction
ii /ucus or mucopurulent plug after surgery
iii +spiration of foreign material
iiii Centrally located bronchogenic carcinoma
b. Cause of al)eolar collapse
,ack of air and distal resorption of pree!isting air through the pores of Fohn in the
al)eolar walls
b. Collapse may in)ol)e all or part of a lung.
ii Clinical findings
a. @e)er and dyspnea
(oth usually occur within 2- to 75 hours of collapse.
b. +bsent breath sounds and )ocal )ibratory sensation (tactile fremitus)
c. Ipsilateral ele)ation of the diaphragm and tracheal de)iation
Collapsed lung gi)es up space, causing the preceding findings.
d. Collapsed lung does not e!pand on inspiration (inspiratory lag).
Compression atelectasis
;. +ir or fluid in the pleural ca)ity under increased pressure collapses small airways beneath the
pleura.
2. %!amples
a. *ension pneumothora! (air compresses lung)
b. "leural effusion (fluid compresses lung)
7. *rachea de)iates to the contralateral side.
+telectasis due to loss of surfactant
Gomen who ha)e to deli)er their babies prematurely recei)e glucocorticoids in order to increase fetal
surfactant synthesis thereby reducing the potential for de)eloping &DD. $ood maternal glycemic control
decreases the risk for &DD.
page 2>7
;. Durfactant
a. Dynthesi0ed by type II pneumocytes
i. Dtored in lamellar bodies
ii. Dynthesis begins in 23th week of gestation.
b. "hosphatidylcholine (lecithin) is the maAor component.
c. Dynthesis is increased by cortisol and thyro!ine.
d. Dynthesis is decreased by insulin.
e. Durfactant reduces surface tension in the small airways.
"re)ents collapse on e!piration, when collapsing pressure is greatest
ii &espiratory distress syndrome (&DD) in newborns
a. "athogenesis
i. Decreased surfactant in the fetal lungs1 causes'
"rematurity
/aternal diabetes
@etal hyperglycemia increases insulin release.
Cesarean section
,ack of stressinduced increase in cortisol from a )aginal deli)ery
ii. Gidespread atelectasis results in massi)e intrapulmonary shunting.
"erfusion without )entilation
b. Collapsed al)eoli are lined by hyaline membranes
Deri)ed from proteins leaking out of damaged pulmonary )essels
b. Clinical findings
i. &espiratory difficulty begins within a few hours after birth.
ii. Infants de)elop hypo!emia and respiratory acidosis.
iii. Chest radiograph shows a Eground glassE appearance.
c. Complications
i. Dupero!ide free radical damage from 82 therapy
/ay result in blindness and permanent damage to small airways
(bronchopulmonary dysplasia)
ii. Intra)entricular hemorrhage
iii. "atent ductus arteriosus (due to persistent hypo!emia)
i). #ecroti0ing enterocolitis
Intestinal ischemia allows entry of gut bacteria into the intestinal wall.
). .ypoglycemia in newborn
%!cess insulin decreases serum glucose producing sei0ures and damage
to neurons.
%cute Lung &n'ury
"ulmonary edema
;. %dema due to alterations in Dtarling pressure (transudate)
a. Increased hydrostatic pressure in pulmonary capillaries
,eftsided heart failure, )olume o)erload, mitral stenosis
b. Decreased oncotic pressure
#ephrotic syndrome, cirrhosis
2. %dema due to micro)ascular or al)eolar inAury (e!udate)
a. Infections (e.g., sepsis, pneumonia)
b. +spiration (e.g., drowning, gastric contents)
c. Drugs (e.g., heroin), shock, massi)e trauma
d. .igh altitude
"ulmonary edema
;. %dema due to alterations in Dtarling pressure (transudate)
a. Increased hydrostatic pressure in pulmonary capillaries
,eftsided heart failure, )olume o)erload, mitral stenosis
b. Decreased oncotic pressure
#ephrotic syndrome, cirrhosis
2. %dema due to micro)ascular or al)eolar inAury (e!udate)
a. Infections (e.g., sepsis, pneumonia)
b. +spiration (e.g., drowning, gastric contents)
c. Drugs (e.g., heroin), shock, massi)e trauma
d. .igh altitude
+cute respiratory distress syndrome (+&DD)
page 2>7
page 2>-
#oncardiogenic pulmonary edema resulting from acute al)eolarcapillary damage.
;. %pidemiology
a. Due to direct inAury to the lungs or systemic diseases
b. &isk factors for +&DD
i. $ramnegati)e sepsis (-6< of cases)
ii. $astric aspiration (76< of cases)
iii. De)ere trauma with shock (;6< of cases)
i). Diffuse pulmonary infections, heroin, smoke inhalation
2. "athogenesis
a. +cute damage to al)eolar capillary walls and epithelial cells
b. +l)eolar macrophages release cytokines.
i. Cytokines are chemotactic to neutrophils.
ii. #eutrophils transmigrate into the al)eoli through pulmonary capillaries.
iii. Capillary damage causes leakage of a proteinrich e!udate producing hyaline
membranes.
i). #eutrophils damage type I and II pneumocytes.
Decrease in surfactant causes atelectasis with intrapulmonary shunting.
c. ,ate findings
i. &epair by type II pneumocytes
ii. "rogressi)e interstitial fibrosis (restricti)e lung disease)
7. Clinical findings
a. Dyspnea with se)ere hypo!emia not responsi)e to 82 therapy
b. +cute respiratory acidosis
4. "oor prognosis (56< mortality rate)
ulmonary &nfections
"neumonia
;. %pidemiology
a. Classified as communityac=uired or nosocomial (hospitalac=uired)
b. Communityac=uired pneumonia is further subdi)ided into typical or
atypical.
2. *ypical communityac=uired pneumonia
a. %pidemiology
i. /aAority are caused by bacterial pathogens.
b. /ost often due to Streptococcus pneumoniae
i. Inhalation of aerosol from an infected patient
ii. +spiration of nasopharyngeal flora while sleeping
c. (ronchopneumonia
i. (egins as an acute bronchitis and spreads locally into the lungs
ii. Bsually in)ol)es the lower lobes or right middle lobe
iii. ,ung has patchy areas of consolidation
/icroabscesses are present in the areas of consolidation.
d. ,obar pneumonia
Complete or almost complete consolidation of a lobe of lung
b. Complications
i. ,ung abscesses, empyema (pus in the pleural ca)ity)
ii. Depsis
b. Clinical findings
i. Dudden onset of high fe)er with producti)e cough
ii. Digns of consolidation (al)eolar e!udate)
Dullness to percussion
Increased )ocal tactile fremitus
Dound is transmitted well through al)eolar
consolidations.
Inspiratory crackles (air mo)ing through e!udate in the
al)eoli)
iii. Chest radiograph (gold standard screen)
"atchy infiltrates (bronchopneumonia) or lobar
consolidation
i). ,aboratory findings
"ositi)e $ram stain
#eutrophilic leukocytosis
7. +typical communityac=uired pneumonia
c. %pidemiology
i. Bsually caused by Mycoplasma pneumoniae
ii. 8ther pathogens
Chlamydia pneumoniae (*G+& agent)
?iruses (respiratory syncytial )irus, influen0a)irus,
adeno)irus)
Chlamydia trachomatis (newborns)
d. "athogenesis
Contracted by inhalation (droplet infection)
b. "atchy interstitial pneumonia
i. /ononuclear infiltrate
ii. +l)eolar spaces usually free of e!udate
e. Clinical findings
i. Insidious onset, lowgrade fe)er, nonproducti)e cough
ii. @lulike symptoms
"haryngitis, laryngitis, myalgias, headache
iii. No signs of consolidation
-. #osocomial pneumonia
f. %pidemiology1 risk factors
i. De)ere underlying disease
ii. +ntibiotic therapy, immunosuppression
iii. &espirators (most common source of infection)
g. "athogens
i. $ramnegati)e bacteria
Pseudomonas aeruginosa (respirators), Escherichia coli
ii. $rampositi)e bacteria (e.g., Staphylococcus aureus)
4. "neumonia in immunocompromised hosts
h. Complication of +IDD and bone marrow transplantation
i. Common opportunistic infections'
i. Cytomegalo)irus (
ii. Pneumocystis jiroveci
*rimethoprimsulfametho!a0ole is used for prophyla!is and
treatment.
iii. Aspergillus fumigatus
5. *uberculosis (*()
A. %pidemiology and pathophysiology
i. Contracted by inhalation of Mycoacterium tuerculosis
ii. Characteristics
Dtrict aerobe, acidfast (due to mycolic acid in cell wall)
iii. Dcreening
"urified protein deri)ati)e (""D) intradermal skin test
Does not distinguish acti)e from inacti)e disease
k. "rimary *(
i. Dubpleural location
Bpper part of the lower lobes or lower part of the upper
lobes
ii. Bsually resol)es
"roduces a calcified granuloma or area of scar tissue
/ay be a nidus for secondary *(
l. Decondary (reacti)ation) *(
i. Due to reacti)ation of a pre)ious primary *( site
ii. In)ol)es one or both apices in upper lobes
?entilation (o!ygenation) is greatest in the upper lobes.
iii. Ca)itary lesion due to release of cytokines from memory * cells
m. Clinical findings
@e)er, drenching night sweats, weight loss
c. Complications
i. /iliary spread in lungs due to in)asion into the bronchus or
lymphatics
ii. /iliary spread to e!trapulmonary sites
Due to in)asion of pulmonary )ein tributaries
Fidney is the most common e!trapulmonary site.
iii. /assi)e hemoptysis, bronchiectasis, scar carcinoma
i). $ranulomatous hepatitis, spread to )ertebra ("ottHs disease)
:. Mycoacterium avium!intracellulare comple! (/+C)
n. +typical mycobacterium
o. /ost common *( in +IDD (often disseminates)
8ccurs when CD- *. count falls below 46 cells/I,
ii Dystemic fungal infections
a. Contracted from inhalation of the pathogen
b. "roduce a granulomatous inflammatory reaction with or without caseation
ii Dummaries of respiratory microbial pathogens
Table 16-(. Summary of Respiratory )icrobial at*ogens
at*ogen Discussion
+iruses
&hino)irus /ost common cause of the common cold
*ransmitted by hand to eyenose contact
&D? /ost common )iral cause of atypical pneumonia and bronchiolitis (whee0ing) in children
8ccurs in late fall and winter
"arainfluen0a /ost common cause of croup (laryngotracheobronchitis) in infants
Inspiratory stridor (upper airway obstruction) due to submucosal edema in trachea
+nterior !ray of neck shows Esteeple sign,E representing mucosal edema in the trachea (site of
obstruction)
C/? Common pneumonia in immunocompromised hosts (e.g., bone marrow transplants, +IDD)
%nlarged al)eolar macrophages/pneumocytes, contain basophilic intranuclear inclusions
surrounded by a halo
Influen0a)irus *ype + )iruses are most often in)ol)ed
.emagglutinins bind )irus to cell receptors in the nasal passages
#euraminidase dissol)es mucus and facilitates release of )iral particles
Influen0a + pneumonia may be complicated by a superimposed bacterial pneumonia (usually
Staphylococcus aureus)
&ubeola @e)er, cough, conAuncti)itis, and e!cessi)e nasal mucus production
Foplik spots in the mouth precede onset of the rash
Garthin@inkeldey multinucleated giant cells are a characteristic finding
D+&D Infects lower respiratory tract and then spreads systemically to produce se)ere respiratory
infection
@irst transmitted to humans through contact with masked palm ci)ets (China) and then from
humantohuman contact through respiratory secretions (e.g., hospitals, families)
Diagnose with )iral detection by "C& or detection of antibodies
Chlamydia
C. pneumoniae Decond most common cause of atypical pneumonia
C. trachomatis #ewborn pneumonia (passage through birth canal)
+febrile, staccato cough (choppy cough), conAuncti)itis, whee0ing
"ic#ettsia
Co$iella urnetii 8nly rickettsia transmitted %ithout a )ector
Contracted by dairy farmers, )eterinarians
+ssociated with the birthing process of infected sheep, cattle, and goats, and handling of milk or
e!crement
+typical pneumonia, myocarditis, granulomatous hepatitis
Mycoplasma
M. pneumoniae /ost common cause of atypical pneumonia
Common in adolescents and military recruits (closed spaces)
Insidious onset with lowgrade fe)er
Complications' bullous myringitis, cold autoimmune hemolytic anemia due to antiIIg/ antibodies
Cold agglutinins in blood
,acteria
Streptococcus
pneumoniae
$rampositi)e lancetshaped diplococcus
/ost common cause of typical community ac=uired pneumonia
&apid onset, producti)e cough, signs of consolidation
Staphylococcus
aureus
$rampositi)e coccus in clumps
Jellow sputum
Commonly superimposed on influen0a pneumonia and measles pneumonia
/aAor lung pathogen in cystic fibrosis and intra)enous drug abusers
.emorrhagic pulmonary edema, abscess formation, and tension pneumatocysts (intrapleural
blebs), which may rupture and produce a tension pneumothora!
Coryneacterium
diphtheriae
$rampositi)e rod
*o!in inhibits protein synthesis by +D"ribosylation of elongation factor 2 in)ol)ed in protein
synthesis1 to!in also impairs Ko!idation of fatty acids in the heart
*o!ininduced pseudomembranous inflammation produces shaggy gray membranes in the
oropharyn! and trachea
Haemophilus
influenzae
$ramnegati)e rod
Common cause of sinusitis, otitis media, conAuncti)itis (pink eye)
Inspiratory stridor may be due to acute epiglottitis1 swelling of epiglottis produces Ethumbprint signE
on lateral !ray of the neck
/ost common bacterial cause of acute e!acerbation of C8"D
Mora$ella
catarrhalis
$ramnegati)e diplococcus
Common cause of typical pneumonia, especially in the elderly
Decond most common pathogen causing acute e!acerbation of C8"D
Common cause of chronic bronchitis, sinusitis, otitis media
Pseudomonas
aeruginosa
$ramnegati)e rod
$reen sputum (pyocyanin)
Gaterlo)ing bacteria most often transmitted by respirators
/ost common cause of nosocomial pneumonia and death due to pneumonia in cystic fibrosis1
pneumonia often associated with infarction due to )essel in)asion
&lesiella
pneumoniae
$ramnegati)e fat rod surrounded by a mucoid capsule
/ost common gramnegati)e organism causing lobar pneumonia and typical pneumonia in elderly
patients in nursing homes
Common cause of pneumonia in alcoholics1 howe)er, S. pneumoniae is still the most common
pneumonia
"neumonia associated with bloodtinged, thick, mucoid sputum1 lobar consolidation and abscess
formation are common
'egionella
pneumophila
$ramnegati)e rod (re=uires I@ stain or Dieterle sil)er stain to identify in tissue)1 antigens can also
be detected in urine
Gaterlo)ing bacteria (water coolers1 mists in produce section of grocery stores1 outdoor
restaurants in summer1 rain forests in 0oos)
"neumonia associated with high fe)er, dry cough, flulike symptoms
/ay produce tubulointerstitial disease with destruction of the Au!taglomerular apparatus leading to
hyporeninemic hypoaldosteronism (type I? renal tubular acidosishyponatremia, hyperkalemia,
metabolic acidosis)
Systemic !ungi
Cryptococcus
neoformans
(udding yeast with narrowbased buds1 surrounded by a thick capsule
@ound in pigeon e!creta (around buildings, outside office windows, under bridges)
/ost common opportunistic fungal infection
"rimary lung disease (-6<)' granulomatous inflammation with caseation
Aspergillus
fumigatus
@ruiting body and narrowangled (L-4 degrees), branching septate hyphae
+spergilloma' fungus ball ()isible on !ray) that de)elops in a pree!isting ca)ity in the lung (e.g.,
old *( site)1 cause of massi)e hemoptysis
+llergic bronchopulmonary aspergillosis' type I and type III hypersensiti)ity reactions1 Ig% le)els
increased1 eosinophilia1 intense inflammation of airways and mucus plugs in terminal bronchioles1
repeated attacks may lead to bronchiectasis and interstitial lung disease
?essel in)ader with hemorrhagic infarctions and a necroti0ing bronchopneumonia
Mucor species Gideangled hyphae (M-4 degrees) without septa
Clinical settings' diabetes, immunosuppressed patients
?essel in)ader and produces hemorrhagic infarcts in the lung
In)ades the frontal lobes in patients with diabetic ketoacidosis (rhinocerebral mucormycosis)
Coccidioides
immitis
Dpherules with endospores in tissues1 contracted by inhaling arthrospores in dust while li)ing or
passing through arid desert areas in the southwestern Bnited Dtates (E)alley fe)erE)1 increased
after earth=uakes (increased dust)
@lulike symptoms and erythema nodosum (painful nodules on lower legs1 inflammation of
subcutaneous fat)
$ranulomatous inflammation with caseous necrosis
Histoplasma
capsulatum
/ost common systemic fungal infection1 endemic in 8hio and central
/ississippi &i)er )alleys1 inhalation of microconidia in dust contaminated with e!creta from bats
(increased incidence in ca)e e!plorers, spelunkers), starlings, or chickens (common in chicken
farmers)
$ranulomatous inflammation with caseous necrosis
Jeast forms are present in macrophages
Dimulates *( lung disease1 produces coin lesions, consolidations, miliary spread, and ca)itation
/arked dystrophic calcification of granulomas1 most common cause of multiple calcifications in the
spleen
(lastomyces
dermatitidis
Jeasts ha)e broadbased buds and nuclei1 occurs in $reat ,akes region and central and
southeastern Bnited Dtates1 maledominant disease
"roduces skin and lung disease1 skin lesions simulate s=uamous cell carcinoma
$ranulomatous inflammation with caseous necrosis
Pneumocystis
jiroveciN
Cysts and tropho0oites present1 cysts attach to type I pneumocytes
"rimarily an opportunistic infection1 occurs when CD- *. count L266
/ost common initial +IDDdefining infection
"atients de)elop fe)er, dyspnea, and se)ere hypo!emia1 diffuse intraal)eolar foamy e!udates
with cupshaped cysts best )isuali0ed with sil)er or $iemsa stains1 chest !ray shows diffuse
al)eolar and interstitial infiltrates
&!' */"/D/O gi)en prophylactically when CD- counts L266 cells/I,
N&ecent nomenclature change from P. carinii.
+D", adenosine diphosphate1 C/?, cytomegalo)irus1 C8"D, chronic obstructi)e pulmonary disease1 I@, immunofluorescence1 "C&,
polymerase chain reaction1 &D?, respiratory syncytial )irus1 D+&D, se)ere acute respiratory syndrome1 *(, tuberculosis1 */"/D/O,
trimethoprimsulfametho!a0ole.
,ung abscess
page 2>3
page 2>>
page 2>>
page 766
page 766
page 76;
page 76;
page 762
page 762
page 767
,$- 16-1 %S&R%T&$. S&T/S &. T0/ LU.1S
@oreign material locali0es to different portions of the lung, depending on the
position of the patient. In the standing or sitting position, material locali0es in the
posterobasal segment of the right lower lobe1 in the supine position, the superior
segment of the right lower lobe1 and in the rightsided position, the right middle
lobe or the posterior segment of the right upper lobe. *he most common
aspiration site is the superior segment of the right lower lobe.
;. Causes of lung abscesses
a. /ost often due to aspiration of oropharyngeal material (e.g., tonsillar material)
i. +erobic and anaerobic streptococci and Staphylococci) Prevotella)
*usoacterium
ii. 8ccurs in patients with depressed cough refle!es (e.g., after anesthesia)
b. Complication of bacterial pneumonia (e.g., Staphylococcus aureus) &lesiella)
c. Deptic embolism (e.g., infecti)e endocarditis)
d. 8bstructi)e lung neoplasia
@rom ;6< to ;4< of abscesses are behind a bronchus obstructed by cancer.
ii $ross findings
a. ?ary in si0e and location
b. *hose due to aspiration are primarily located on the right side
ii Clinical findings
a. Dpiking fe)er with producti)e cough (foulsmelling sputum)
b. Chest radiograph shows ca)itation with an airfluid le)el.
+ascular Lung Lesions
"ulmonary thromboembolism
page 76-
In a patient with normal bronchial artery blood flow (originates from thoracic aorta
and intercostal arteries) and )entilation, a pulmonary embolus produces a
hemorrhagic infarction in ;6< of cases. .owe)er, if the patient has decreased
bronchial artery blood flow (e.g., decreased cardiac output), or pre)iously
under)entilated lung (e.g., obstructi)e lung disease), then occlusion of the
pulmonary )essel will likely result in a hemorrhagic infarction, which significantly
increases risk of morbidity and death.
;. %pidemiology and pathogenesis
a. Dource
/aAority (>4<) originate in the femoral )ein
b. &isk factors for thromboembolism
Dtasis of blood flow (e.g., prolonged bed rest), hypercoagulable states
c. Di0e of the embolus determines pulmonary )essel that is occluded.
ii ,arge emboli occlude the maAor )essels (saddle embolus)
iii Dmall emboli occlude mediumsi0ed and small pulmonary arteries.
b. "otential conse=uences of pulmonary artery occlusion
ii Increase in pulmonary artery pressure
iii Decrease blood flow to pulmonary parenchyma
/ay cause hemorrhagic infarction.
2. &edblue, raised, wedgeshaped area that e!tends to the pleural surface
a. "leural surface has a fibrinous e!udate (produces a pleural friction rub).
.emorrhagic pleural effusion may also occur.
b. /aAority are located in the lower lobes.
"erfusion is greater than )entilation in the lower lobes.
ii Clinical findings
a. Daddle embolus
ii Dudden increase in pulmonary artery pressure
iii "roduces acute right )entricular strain and sudden death
b. "ulmonary infarction
ii Dudden onset of dyspnea and tachypnea
iii @e)er
iiii "leuritic chest pain (pain on inspiration), friction rub, effusion
2. ,aboratory findings with a pulmonary infarction
a. &espiratory alkalosis (arterial "C82 L77 mm .g)
b. "a82 less than 36 mm .g (>6< of cases)
c. Increase in +a gradient (;66< of cases)
d. +bnormal perfusion radionuclide scan
ii ?entilation scan is normal, but the perfusion scan is abnormal.
iii "ulmonary angiogram is gold standard confirmatory test.
e. "ositi)e Ddimers
"ulmonary hypertension (".)
page 76-
page 764
;. %pidemiology and pathogenesis
a. "rimary ".
i. "rimary type is more common in women.
ii. ?ascular hyperreacti)ity with proliferation of smooth muscle
b. Decondary ".
i. %ndothelial cell dysfunction
,oss of )asodilators (e.g., nitric o!ide), increase in )asoconstrictors (e.g.,
endothelin)
ii. .ypo!emia and/or respiratory acidosis stimulate )asoconstriction of pulmonary
arteries.
Causes smooth muscle hyperplasia and hypertrophy
iii. Causes
Chronic hypo!emia (e.g., chronic lung disease)
Chronic respiratory acidosis (e.g., chronic bronchitis)
,oss of pulmonary )asculature (e.g., emphysemal)
Increases workload for remaining )essels
,efttoright cardiac shunts
/itral stenosis
(ackup of blood into the pulmonary )eins
2. "athologic findings
a. +therosclerosis of main elastic pulmonary arteries
Due to increased pressure on the endothelium leading to inAury
b. "roliferation of myointimal cells and smooth muscle cells
ii Clinical findings
a. "rogressi)e dyspnea and chest pain with e!ertion
b. Chest radiograph shows tapering of the pulmonary arteries
c. +ccentuated "2 (sign of ".)
d. ,eft parasternal hea)e (sign of right )entricular hypertrophy, &?.)
". imposes an increased afterload on the right )entricle.
e. &ightsided heart failure due to cor pulmonale
ii Cor pulmonale
o Combination of ". and right &?. leading to rightsided heart failure
$oodpasture syndrome
"ulmonary hemorrhage with hemoptysis often precedes renal failure.
Restricti#e Lung Diseases
*hese disorders are characteri0ed by reduced total lung capacity in the presence of a normal or
reduced e!piratory flow rate.
Causes of restricti)e disease
;. Chest wall disorders in the presence of normal lungs
o %!ampleskyphoscoliosis, pleural disease (e.g., mesothelioma), obesity
2. +cute or chronic interstitial lung diseases
a. +cute interstitial disease (e.g., +&DD, see section ?)
b. Chronic interstitial disease
i. @ibrosing disorders (e.g., pneumoconiosis)
ii. $ranulomatous disease (e.g., sarcoidosis)
"athogenesis of interstitial fibrosis
;. %arliest manifestation is an al)eolitis.
o ,eukocytes release cytokines, which stimulate fibrosis.
2. %ffects of interstitial fibrosis
a. Decreases lung compliance
i. Decreased e!pansion of the lung parenchyma during inspiration
ii. Damage to type I/II al)eolar cells and endothelial cells
@unctional loss of al)eolar and capillary units
b. Increases lung elasticity
&ecoil of the lung on e!piration is increased.
2. Clinical and laboratory findings in all restricti)e lung diseases
ii Dry cough and e!ertional dyspnea
ii ,ate inspiratory crackles in lower lung fields
ii "otential for cor pulmonale
ii "ulmonary function test findings and arterial blood gases
i. +ll )olumes and capacities are e=ually decreased.
ii. Decreased @%?;sec
%!ample7, (normal -,)
iii. Decreased @?C
8ften the same )alue as @%?;sec (7,) due to increased lung elasticity
i). Increased ratio of @%?;sec/@?C
%!ample7/7 9 ;66< (normal is 36<)
). &espiratory alkalosis (arterial "C82 L 77 mm .g)
)i. Decreased "a82
b. Chest radiograph findings
Diffuse bilateral reticulonodular infiltrates
"neumoconioses
;. %pidemiology
a. Inhalation of mineral dust into the lungs leading to interstitial fibrosis
i. /ineral dust includes coal dust, silica, asbestos, and beryllium.
ii. +ccounts for 24< of cases of chronic interstitial lung disease
b. "article si0e determines site of lung deposition
i. ; to 4Im particles
&each the bifurcation of the respiratory bronchioles and al)eolar ducts
ii. Dmaller than 6.4Im particles
&each the al)eoli and are phagocytosed by al)eolar macrophages
c. Coal dust is the least fibrogenic particle.
d. Dilica, asbestos, and beryllium are )ery fibrogenic.
2. Coal workerHs pneumoconiosis (CG")
a. Dources of coal dust (anthracotic pigment)
Coal mines, large urban centers, tobacco smoke
b. "ulmonary anthracosis
i. Bsually asymptomatic
ii. +nthracotic pigment in interstitial tissue and hilar nodes
+l)eolar macrophages with anthracotic pigment are called Edust cells.E
b. Dimple CG"
i. @ibrotic opacities are smaller than ;cm in upper lobes and upper portions of
lower lobes.
ii. Coal deposits adAacent to respiratory bronchioles produce centrilobular
emphysema (see section IO).
c. Complicated CG" (progressi)e massi)e fibrosis)
i. @ibrotic opacities larger than ; to 2cm with or without necrotic centers
ii. Crippling lung disease (Eblack lungE disease)
iii. No increased incidence of *( or primary lung cancer
i). Cor pulmonale may occur.
). Caplan syndrome may occur.
CG" plus large ca)itating rheumatoid nodules in the lungs
7. Dilicosis
d. %pidemiology
i. /ost common occupational disease in the world
ii. Puart0 (crystalline silicone dio!ide) is most often implicated
Dources' foundries (casting metal), sandblasting, working in mines
e. "athogenesis
i. Puart0 is highly fibrogenic and deposits in the upper lungs.
ii. Puart0 acti)ates and is cytolytic to al)eolar macrophages.
/acrophages release cytokines that stimulate fibrogenesis.
f. Chronic e!posure
i. #odular opacities in the lungs
Concentric layers of collagen with or without central ca)itation
Puart0 polari0es in the nodules.
ii. E%ggshellE calcification in hilar nodes
&im of dystrophic calcification in the nodes
g. Complications
i. Cor pulmonale, Caplan syndrome
ii. Increased risk for de)eloping lung cancer and *(
-. +sbestosrelated disease
h. $eometric forms of asbestos
i. Derpentine
Curly and fle!ible fibers (e.g., chrysotile)
"roduces interstitial fibrosis and lung cancer
ii. +mphibole
Dtraight and rigid (e.g., crocidolite)
"roduces interstitial fibrosis, lung cancer, mesothelioma
iii. Deposition sites
&espiratory bronchioles, al)eolar ducts, al)eoli
i. Dources
i. Insulation around pipes in old na)al ships
ii. &oofing material used o)er 26 years ago
iii. Demolition of old buildings
A. +ppearance in tissue
i. @ibers are coated by iron and protein (called ferruginous bodies)
/acrophages phagocytose and coat the fibers with ferritin.
ii. $olden, beaded appearance in sputum or in distal, small airways
k. +sbestosrelated disease
i. (enign pleural pla=ues
Calcified pla=ues on the pleura and dome of the diaphragm
*hey are not a precursor lesion for a mesothelioma.
ii. Diffuse interstitial fibrosis with or without pleural effusions
iii. "rimary bronchogenic carcinoma
&isk further increases if the patient smokes cigarettes.
8ccurs 26 years after first e!posure.
i). /alignant mesothelioma of pleura
No etiologic relationship with smoking
+rises from the serosal cells lining the pleura
%ncases and locally in)ades the subpleural lung tissue
8ccurs 24 to -6 years after first e!posure
). No increased risk for *(
l. Complications
Cor pulmonale, Caplan syndrome
ii (erylliosis
a. %!posure in the nuclear and aerospace industry
b. Diffuse interstitial fibrosis with noncaseating granulomas
c. Increased risk for cor pulmonale and primary lung cancer
Darcoidosis
page 7;;
/ultisystem granulomatous disease of unknown etiology
;. %pidemiology
a. +ccounts for 24< of cases of chronic interstitial lung disease
b. Common in black +mericans and nonsmokers
2. "athogenesis
a. Disorder in immune regulation
b. CD- *. cells interact with an unknown antigen.
&eleases cytokines causing formation of noncaseating granulomas
c. Diagnosis of e!clusion
/ust rule out other granulomatous diseases
7. ,ung disease
a. "rimary target organ
ii $ranulomas located in the interstitium and mediastinal and hilar nodes
iii $ranulomas contain multinucleated giant cells
Contain laminated calcium concretions (Dchaumann bodies) and stellate
inclusions (called asteroid bodies)
b. Dyspnea is the most common symptom.
2. Dkin lesions
a. #odular lesions containing granulomas
b. ?iolaceous rash occurs on the nose and cheeks (called lupus pernio).
c. %rythema nodosum
ii "ainful nodules on lower e!tremities
iii Inflammation of subcutaneous fat
7. %ye lesions1 produces u)eitis'
o (lurry )ision, glaucoma, and corneal opacities
2. ,i)er lesions
o $ranulomatous hepatitis
3. 8ther multisystem findings
a. %nlarged sali)ary and lacrimal glands
b. Diabetes insipidus (hypothalamic and/or posterior pituitary disease)
c. $ranulomas in the bone marrow and spleen
2. ,aboratory findings
a. Increased angiotensincon)erting en0yme (+C%)
ii $ood marker of disease acti)ity and response to corticosteroid therapy
b. .ypercalcemia (4< of cases)
ii Increased synthesis of ;Qhydro!ylase in granulomas (hyper)itaminosis D)
c. 8ther findings
ii "olyclonal gammopathy
iii Cutaneous anergy to common skin antigens (e.g., Candida)
Due to consumption of CD- *. cells in granulomas and loss of cells in
al)eolar secretions
2. Chest radiograph
a. %nlarged hilar and mediastinal lymph nodes (called Epotato nodesE)
b. &eticulonodular densities throughout the lung parenchyma
2. "rognosis
a. "rogressi)e disease or intermittent disease with periods of acti)ity and remissions
b. (etween ;6< and ;4< de)elop se)ere interstitial fibrosis, leading to cor pulmonale and death.
Idiopathic pulmonary fibrosis
;. %pidemiology
a. +ccounts for ;4< of cases of chronic interstitial lung disease
b. /ore common in males than in females
c. Bsually occurs in indi)iduals o)er -6 to :6 years old
2. "athogenesis
a. &epeated cycles of al)eolitis triggered by an unknown agent
b. &elease of cytokines produces interstitial fibrosis
7. +l)eolar fibrosis leads to pro!imal dilation of the small airways.
o ,ung has a honeycomb appearance.
Collagen )ascular diseases
+ny une!plained pleural effusion in a young woman is D,% until pro)ed otherwise.
"leural fluid contains an inflammatory infiltrate (e!udate), and ,% cells (neutrophils
with phagocytosed D#+) are sometimes present. 8ne of the key criteria for
diagnosing D,% is the presence of serositis, pleuritis with a pleural effusion being an
e!ample of this type of inflammation.
;. +ccount for ;6< of cases of chronic interstitial lung disease
2. Dystemic sclerosis
o /ost common cause of death is lung disease.
7. Dystemic lupus erythematosus (D,%)
a. Interstitial lung disease occurs in 46< of patients.
b. "leuritis with pleural effusions
2. &heumatoid arthritis (&+)
a. &heumatoid nodules in lungs plus a pneumoconiosis is called Caplan syndrome.
b. "ulmonary findings in &+
i. Interstitial fibrosis with or without intrapulmonary rheumatoid nodules
ii. "leuritis with pleural effusions
.ypersensiti)ity pneumonitis
page 7;;
page 7;2
;. %!trinsic allergic al)eolitis associated with e!posure to a #no%n inhaled antigen
o Does not in)ol)e Ig% antibodies (type I hypersensiti)ity) or ha)e eosinophilia
2. @armerHs lung
a. %!posure to Saccharopolyspora rectivirgula (thermophilic actinomycetes bacteria) in
moldy hay
b. @irst e!posure
"atient de)elops precipitating Ig$ antibodies (present in serum)
c. Decond e!posure
ii +ntibodies combine with inhaled allergens to form immune comple!es.
*ype III hypersensiti)ity reaction
iii Immunocomple!es produce an inflammatory reaction in lung tissue.
b. Chronic e!posure
+dditional component of granulomatous inflammation (type I? hypersensiti)ity)
2. Dilo fillerHs disease
ii Inhalation of wheat wee)il protein
ii Causes an immediate hypersensiti)ity reaction associated with dyspnea
7. (yssinosis
ii %pidemiology
ii 8ccurs in workers in te!tile factories
iii Contact with cotton, linen, hemp products
b. Clinical findings
ii De)elop dyspnea on e!posure to cotton, linen, or hemp products
iii Gorkers feel better o)er the weekend (no e!posure to antigens)
Depression occurs when returning to work on /onday (E/onday morning
bluesE)
Drugs associated with interstitial fibrosis
;. +miodarone
2. (leomycin and busulfan
7. Cyclophosphamide
-. /ethotre!ate and methysergide
4. #itrosourea and nitrofurantoin
&adiationinduced lung disease
;. +cute pneumonitis may occur ; to 5 months after therapy.
2. Clinical findings
o @e)er, dyspnea, pleural effusions, and radiologic infiltrates
7. Dome patients de)elop chronic radiation pneumonitis.
$bstructi#e Lung Disease
8bstruction to airflow out of the lungs
page 7;-
page 7;4
;. "ermanent enlargement of all or part of the respiratory unit
o &espiratory bronchioles, al)eolar ducts, al)eoli
2. %pidemiology
a. Causes
i. Cigarette smoking is the most common cause.
ii. Q;+ntitrypsin (++*) deficiency
b. *ypes of emphysema associated with smoking or loss of ++*
i. Centriacinar (centrilobular) emphysema
ii. "anacinar emphysema
2. "athogenesis
a. Increased compliance and decreased elasticity
i. Imbalance between elastase and antielastases (e.g., Q;antitrypsin, ++*)
ii. Imbalance between o!idants (free radicals) and antio!idants (e.g., glutathione)
iii. %lastase and o!idants deri)e from neutrophils and macrophages.
i). #et effect of the preceding is destruction of elastic tissue.
b. Cigarette smoke is chemotactic to neutrophils and macrophages.
*hey accumulate in the respiratory unit and release free radicals and elastases.
ii @ree radicals in cigarette smoke inacti)ate ++* and antio!idants.
"roduces a functional ++* deficiency
ii #ormal function of elastic tissue
i. @ibers attach to the outside wall of the small airways
ii. @ibers apply radial traction to keep the airway lumens open.
b. Destruction of elastic tissue causes loss of radial traction.
Dmall airways collapse, particularly on e!piration.
ii Dites of elastic tissue destruction in emphysema
i. Distal terminal bronchiole at its Aunction with the respiratory bronchiole (&()
ii. +ll or part of the respiratory unit
c. Dite of obstruction and air trapping in emphysema
i. During e!piration, the distal terminal bronchioles collapse pre)enting egress of air
out of the respiratory unit.
ii. *rapped air distends parts of the respiratory unit that ha)e lost their elastic tissue
support.
2. Centriacinar (centrilobular) emphysema (see
a. %pidemiology
/ost common type of emphysema in smokers
ii "athogenesis
i. "rimarily in)ol)es the apical segments of the upper lobes
ii. Distal terminal bronchioles and the &(s are the sites of elastic tissue destruction.
iii. +ir trapped behind the collapsed distal terminal bronchioles distends the &(s.
*he trapped air increases &? and *,C.
7. "anacinar emphysema
a. %pidemiology
i. +ssociated with ++* deficiency
$enetic or ac=uired causes (cigarette smoke inacti)ates ++*)
ii. $enetic type of ++* deficiency
+utosomal recessi)e disorder
// phenotype is normal.
#ormal amounts of ++* are synthesi0ed in the li)er.
RR phenotype has decreased synthesis of ++* by the li)er.
iii. %mphysema de)elops at an early age in the genetic type.
b. "athogenesis
i. "rimarily affects the lower lobes
ii. Distal terminal bronchioles and all parts of the respiratory units are the sites of
elastic tissue destruction.
iii. +ir trapped behind the collapsed terminal bronchioles distends the entire
respiratory unit.
c. ,aboratory finding
+bsent Q;globulin peak in a serum protein electrophoresis
2. Clinical findings in centriacinar and panacinar emphysema
ii "rogressi)e dyspnea and hyper)entilation
i. Dyspnea is se)ere and occurs early in the disease.
ii. Dometimes patients are called Epink puffers.E
d. Centriacinar type fre=uently coe!ists with chronic bronchitis.
e. (reath sounds are diminished due to hyperinflation.
f. Cor pulmonale is uncommon.
-. Chest radiograph
a. .yperlucent lung fields
b. Increased anteroposterior diameter
c. ?ertically oriented heart
d. Depressed diaphragms due to hyperinflated lungs
4. "ulmonary function tests and arterial blood gases
a. Increased *,C due to an increase in &?
b. Decreased @%?;sec (e.g., ;, )ersus -,1 see
c. Decreased @?C (e.g., 7, )ersus 4,1 see
Decreased @%?;sec/@?C ratio (e.g., ;/7 9 77<)
ii Decreased "a82 de)elops late in the disease.
Destruction of the capillary bed matches destruction of the respiratory unit
ii #ormal to decreased arterial "C82 (respiratory alkalosis)
7. 8ther types of emphysema unrelated to smoking or ++* deficiency
ii "araseptal emphysema
i. ,ocali0ed disease in a subpleural location
"rimarily targets the al)eolar ducts and al)eoli
ii. Does not produce obstructi)e airway disease
iii. Increased incidence of spontaneous pneumothora!
Due to rupture of subpleural blebs
d. Irregular emphysema
i. ,ocali0ed disease is associated with scar tissue.
ii. Does not produce obstructi)e airway disease
Chronic bronchitis
page 7;4
page 7;5
*urbulent airflow in the bronchi is con)erted to laminar airflow in the terminal
(nonrespiratory) bronchioles. *he terminal bronchioles undergo parallel branching,
which reduces airflow resistance and spreads air out o)er a large crosssectional
area. Dmall airway disease associated with e!piratory whee0ing is due to narrowing
of the terminal bronchioles by mucus plugs, inflammation, and fibrosis. /ucus plugs
located in a pro!imal terminal bronchiole pre)ent the e!odus of a large amount of
C82 arising from the distally located airways producing respiratory acidosis.
page 7;5
page 7;:
;. %pidemiology
a. "roducti)e cough for at least 7 months for 2 consecuti)e years
b. Causes
i. Dmoking cigarettes
ii. Cystic fibrosis
2. "athogenesis
a. .ypersecretion of mucus in bronchi
b. 8bstruction to airflow in the terminal bronchioles
+irflow obstruction is pro!imal to the obstruction in emphysema.
b. Irre)ersible fibrosis of terminal bronchioles
c. Changes in the bronchi
i. .ypersecretion of submucosal mucussecreting glands in trachea and bronchi
"rimarily responsible for sputum o)erproduction
ii. +cute inflammation (neutrophils) often superimposed on chronic inflammation
iii. ,oss of ciliated epithelium and presence of s=uamous metaplasia
b. Changes in the terminal bronchioles
i. /ucus plugs in lumens (block the e!odus of C82)
ii. $oblet cell metaplasia
iii. .ypertrophy of mucoussecreting glands
i). Chronic inflammation and fibrosis narrowing the lumen
7. Clinical findings
c. "roducti)e cough
d. Dyspnea occurs late in the disease.
e. Cyanosis of skin and mucous membranes
i. Decreased 82 saturation from hypo!emia
ii. "atients are called Eblue bloaters.E
f. *end to be stocky or obese
g. %!piratory whee0ing and sibilant rhonchi
h. Cor pulmonale is commonly present.
-. Chest radiograph
i. ,arge, hori0ontally oriented heart
A. Increased bronchial markings
4. "ulmonary function tests and arterial blood gases
k. ,ess increase in *,C and &? than emphysema
l. Chronic respiratory acidosis
i. +rterial "C82 greater than -4 mm .g
ii. (icarbonate greater than 76 m%=/,
m. /oderate to se)ere hypo!emia early in the disease
5. Dummary of findings in chronic bronchitis and emphysema
Table 16-2. Comparison of /mp*ysema and C*ronic ,ronc*itis
arameter /mp*ysema C*ronic ,ronc*itis
"a82 Decreased Decreased
"aC82 #ormal to decreased Increased
p. #ormal to increased Decreased
Cyanosis +bsent "resent
.abitus *hin Dtocky
Cor pulmonale &are Common
8nset of hypo!emia ,ate %arly
8nset of dyspnea %arly ,ate
+sthma
page 7;:
page 7;3
80one (87) is an air pollutant that deri)es from interactions of 82 with o!ides of
nitrogen and sulfur, and hydrocarbons. It forms highly reacti)e free radicals in the
airways that cause inflammation and irritation, often precipitating asthma.
;. %pidemiology
a. %pisodic and re)ersible airway disease
b. "rimarily targets the bronchi and terminal bronchioles
c. /ost common chronic respiratory disease in children
d. %!trinsic and intrinsic types
2. %!trinsic asthma
a. "athogenesis
i. *ype I hypersensiti)ity reaction with e!posure to e!trinsic allergens
*ypically de)elops in children with an atopic family history to allergies
ii. Initial sensiti0ation to an inhaled allergen
Dtimulate induction of subset 2 helper * cells (CD- *.2) that release
interleukin (I,) - and I,4
I,- stimulates isotype switching to Ig% production.
I,4 stimulates production and acti)ation of eosinophils.
iii. Inhaled antigens crosslink Ig% antibodies on mast cells on mucosal surfaces.
&elease of histamine and other preformed mediators
@unctions of mediators
Dtimulate bronchoconstriction, mucus production, influ! of
leukocytes
i). ,ate phase reaction (-3 hours later)
%ota!in is produced.
Chemotactic for eosinophils and acti)ates eosinophils
%osinophils release maAor basic protein and cationic protein.
Damage epithelial cells and produce airway constriction
b. 8ther mediators in)ol)ed
i. ,*CD%- cause prolonged bronchoconstriction.
ii. +cetylcholine causes airway muscle contraction.
c. .istologic changes in bronchi
i. *hickening of the basement membrane
ii. %dema and a mi!ed inflammatory infiltrate
iii. .ypertrophy of submucosal glands
i). .ypertrophy/hyperplasia of smooth muscle cells
d. .istologic changes in the terminal bronchioles
i. @ormation of spiralshaped mucus plugs
Contain shed epithelial cells called Curschmann spirals
"athologic effect of maAor basic protein and cationic protein
ii. Crystalline granules in eosinophils coalesce to form Charcot,eyden crystals.
iii. "atchy loss of epithelial cells, goblet cell metaplasia
i). *hick basement membrane
). Dmooth muscle cell hypertrophy and hyperplasia
e. Clinical findings
i. %pisodic e!piratory whee0ing (inspiratory as well when se)ere)
ii. #octurnal cough
iii. Increased anteroposterior diameter
Due to air trapping and increase in residual )olume
f. ,aboratory findings
i. Initially de)elop respiratory alkalosis
"atients work hard at e!pelling air through inflamed airways.
/ay progress into respiratory acidosis if bronchospasm is not relie)ed
&espiratory acidosis is an indication for intubation and
mechanical )entilation.
ii. %osinophilia, positi)e skin tests for allergens
g. *reatment of mild disease
/etereddose inhaler with a K2agonist (e.g., albuterol)
b. *reatment of more ad)anced disease
i. /etered lowdose inhaler with corticosteroids
ii. Bse of leukotriene inhibitors
7. Intrinsic asthma
b. #onimmune
c. Causes
i. ?irusinduced respiratory infection
%!amplesrhino)irus, parainfluen0a )irus, respiratory syncytial )irus
ii. +ir pollutants
iii. +spirin or nonsteroidal drug sensiti)ity (see section III)
i). Dtress, e!ercise, cigarette smoke
(ronchiectasis
page 7;>
page 726
;. %pidemiology and pathogenesis
a. "ermanent dilation of the bronchi and bronchioles
Due to destruction of cartilage and elastic tissue by chronic necroti0ing infections
b. Causes
ii Cystic fibrosis
/ost common cause in the Bnited Dtates
iii Infections
*( is the most common cause worldwide.
+deno)irus, Staphylococcus aureus) Hemophilus influenzae
iiii (ronchial obstruction
%!amplepro!imally located bronchogenic carcinoma occludes the
lumen.
ivi "rimary ciliary dyskinesia
+bsent dynein arm in cilia
Dynein arm contains +*"ase (adenosine triphosphatase) for mo)ement
of the cilia.
vi +llergic bronchopulmonary aspergillosis
2. $ross findings
a. /ost commonly occurs in the lower lobes
b. Dilated bronchi and bronchioles are filled with pus
ii Dilated airways e!tend to the lung periphery.
iii Dilations are tubelike and/or saccular.
7. Clinical findings
a. Cough producti)e of copious sputum (often cupfuls)
b. .emoptysis that is sometimes massi)e
c. Digital clubbing, cor pulmonale
-. Chest radiograph findings
o Crowded bronchial markings e!tend to the lung periphery.
2. Cystic fibrosis (C@)
a. %pidemiology
ii +utosomal recessi)e disease
iii "rimarily affects whites
Bncommon in +sians and black +mericans
b. "athogenesis
ii *hree nucleotide deletion on chromosome :
#ucleotides normally code for phenylalanine.
iii "roduction of a defecti)e C@ transmembrane conductance regulator (C@*&) for
chloride ions
iiii C@*& Cl

is degraded in the $olgi apparatus.

Due to defecti)e protein folding
ivi ,oss of C@*& Cl

causes decreased #a
S
and Cl

reabsorption in sweat glands.

(asis of the sweat test
vi %ffect of loss of C@*& Cl

in other secretions
Increased #a
S
and water reabsorption from luminal secretions
Decreased Cl

secretion out of epithelial cells into luminal secretions

#et effect is dehydration of body secretions due to lack of #aCl
Decretions are dehydrated in bronchioles, pancreatic ducts, bile
ducts, meconium, and seminal fluid.
c. Clinical findings
ii #asal polyps (24< of cases)
iii &espiratory infections/failure
Pseudomonas aeruginosa is the most common respiratory pathogen.
8ther common pathogensS. aureus) H. influenzae
Cor pulmonale commonly occurs.
iiii /alabsorption
"ancreatic e!ocrine deficiency
+trophy of glands from dehydrated secretions blocking the lumens
ivi *ype ; diabetes mellitus
Due to chronic pancreatitis
vi Infertility in males
+tresia of )as deferens
vii /econium ileus
Dmall bowel obstruction in newborn
viii Decondary biliary cirrhosis
Due to obstruction of bile ductules by thick secretions
Lung Tumors
"rimary lung cancer is the most common cancer killer in both men and women.
%pidemiology
;. Incidence of lung cancer is declining in men but increasing in women.
2. "eak incidence is at 44 to 54 years of age.
7. Causes
a. Cigarette smoking
b. &adon gas (uranium mining)
c. +sbestos, chromium, nickel, beryllium, arsenic, )inyl chloride
-. "rimary lung cancer in decreasing incidence
a. +denocarcinoma
b. D=uamous cell carcinoma
c. Dmall cell lung carcinoma
d. ,arge cell carcinoma
e. (ronchial carcinoid
4. D=uamous and small cell lung carcinomas
a. $reatest smoking association
b. *end to be centrally located (i.e., main stem bronchus)
5. +denocarcinomas
a. Geakest smoking association
b. *end to be more peripherally located
*umor and tumorlike disorders
Table 16-3. Tumors and Tumor-li4e Disorders of t*e Lung
Type of Tumor or
Disorder
Location in
Lung Comments
+denocarcinoma "eripheral /ore common in women
+ssociated with cigarette smoking
*umors may de)elop in scars or spread along al)eolar walls and mimic
lobar pneumonia (bronchioloal)eolar)
D=uamous cell carcinoma Central /ore common in men
Dtrong association with cigarette smoking
*end to ca)itate
/ay ectopically secrete "*.related protein
Dmall cell carcinomaN Central /ore common in men
Dtrong association with cigarette smoking
+rise from neuroendocrine cells (Fulchitsky cells)
&apidly growing cancer that metastasi0es early
/ay ectopically secrete +D. or +C*.
,arge cell carcinoma "eripheral Bndifferentiated cancer that metastasi0es early
(ronchial carcinoid Central No association with cigarette smoking
,owgrade cancer of neuroendocrine origin
Carcinoid syndrome is rare (does not re=uire li)er metastasis)
Carcinoma metastatic to
the lung
/ultifocal /ore common than primary cancer
Bsually presents with dyspnea
(ronchial hamartoma Central #onneoplastic proliferation of cartilage and adipose tissue
+ppears as solitary EcoinE lesion on chest radiograph
NDee
+C*., adrenocorticotropic hormone1 +D., antidiuretic hormone1 "*., parathyroid hormone.
+ solitary pulmonary nodule or coin lesion is the term applied to a peripheral lung
nodule smaller than 4cm. Causes of a solitary pulmonary nodule in descending
order include granulomas (e.g., *(, histoplasmosis), malignancy (usually primary
cancer), and a bronchial (chondroid) hamartoma. "atients younger than 74 years
old ha)e a ;< risk of a solitary coin lesion representing a malignancy, but patients
46 years old and up ha)e a 46< to 56< risk of malignancy, usually a primary
cancer. In e)aluating solitary coin lesions, comparing pre)ious chest !rays for
changes in si0e of the nodule is the most important initial step.
/etastatic cancer
;. %pidemiology
a. /ost common lung cancer
b. Cancers most often responsible for metastasis
i. "rimary breast cancer most common cause
ii. Colon cancer, renal cell carcinoma
2. Dites of lung metastasis
a. "arenchyma
b. "leura and pleural space (malignant effusions)
c. ,ymphatics (causes se)ere dyspnea)
7. Dyspnea is the most common symptom.
Clinical findings in primary lung cancer
page 72;
page 722
page 722
page 727
page 727
page 72-
;. Cough is the most common symptom (:4< of cases).
;. Dyspnea, hemoptysis, weight loss, chest pain
2. "ancoast tumor (superior sulcus tumor)
a. Bsually a primary s=uamous cancer located at the e!treme ape! of lung
b. Destruction of superior cer)ical sympathetic ganglion produces .ornerHs
syndrome
i. Ipsilateral lid lag
ii. /iosis (pinpoint pupil)
iii. Ipsilateral anhydrosis (lack of sweating)
7. Duperior )ena ca)a syndrome
-. "araneoplastic syndromes
a. Digital clubbing
Due to reacti)e periosteal changes in the underlying bone
ii /uscle weakness (%aton,ambert syndrome)
ii %ctopic hormone secretion (see abo)e)
Common sites for metastasis
;. .ilar lymph nodes most common site
2. +drenal gland (46< of cases)
7. ,i)er (76< of cases), brain (26< of cases), bone (usually osteolytic)
"rognosis
;. #onsmall cell cancers fare better than small cell carcinoma.
2. 8)erall combined 4year sur)i)al rate is ;4<.
)ediastinum Disorders
/ediastinal masses
page 72-
page 724
;. %pidemiology
a. Bsually metastatic primary lung cancer in older patients
b. Bsually primary disease in younger patients
c. +nterior compartment is the most common site.
d. /ost common primary mediastinal masses, in descending order'
i. #eurogenic tumors
Bsually malignant in children and benign in adults
ii. *hymomas (see below)
iii. "rimary cysts
Bsually a pericardial cyst
i). /alignant lymphomas
Bsually nodular sclerosing .odgkinHs lymphoma in a woman
). *eratoma
2. *hymoma
a. %pidemiology
i. ,ocated in the anterior mediastinum
ii. (enign (:6<), malignant (76<)
b. %pithelium, not lymphoid tissue, is the neoplastic component.
c. /aAority e!press systemic symptoms of myasthenia gra)is
i. ,ess than ;6< to ;4< of myasthenia patients ha)e a thymoma.
ii. /aAority (54:4<) ha)e follicular ( cell hyperplasia in the thymus.
Dite for synthesis of antiacetylcholine receptor antibodies
d. 8ther thymoma associations
i. .ypogammaglobulinemia, pure &(C aplasia
ii. Increased incidence of autoimmune disease (e.g. $ra)esH disease
/ediastinal masses
page 72-
page 724
;. %pidemiology
a. Bsually metastatic primary lung cancer in older patients
b. Bsually primary disease in younger patients
c. +nterior compartment is the most common site.
d. /ost common primary mediastinal masses, in descending order'
i. #eurogenic tumors
Bsually malignant in children and benign in adults
ii. *hymomas (see below)
iii. "rimary cysts
Bsually a pericardial cyst
i). /alignant lymphomas
Bsually nodular sclerosing .odgkinHs lymphoma in a woman
). *eratoma
2. *hymoma
a. %pidemiology
i. ,ocated in the anterior mediastinum
ii. (enign (:6<), malignant (76<)
b. %pithelium, not lymphoid tissue, is the neoplastic component.
c. /aAority e!press systemic symptoms of myasthenia gra)is (
i. ,ess than ;6< to ;4< of myasthenia patients ha)e a thymoma.
ii. /aAority (54:4<) ha)e follicular ( cell hyperplasia in the thymus.
Dite for synthesis of antiacetylcholine receptor antibodies
d. 8ther thymoma associations
i. .ypogammaglobulinemia, pure &(C aplasia
ii. Increased incidence of autoimmune disease (e.g. $ra)esH disease)
leural Disorders
/o)ement of pleural fluid
#ormally mo)es from parietal pleura into the pleural space and into the lungs
/o)ement
of pleural
fluid
#ormally mo)es from parietal pleura into the pleural space and into the lungs
Causes
of
pleural
effusion
;. Increased hydrostatic pressure in the )isceral pleura (e.g., congesti)e heart failure)
2. Decreased oncotic pressure (e.g., nephrotic syndrome)
7. 8bstruction of lymphatic drainage from the )isceral pleura (e.g., lung cancer)
-. Increased )essel permeability of )isceral pleural capillaries (e.g., infarction)
4. /etastasis to the pleura (e.g., metastatic breast cancer)
*ypes of pleural effusions
;. *ransudates
a. Bltrafiltrate of plasma in)ol)ing disturbances in Dtarling pressures
b. %!ampleincreased hydrostatic pressure or decreased oncotic pressure
2. %!udates
a. "roteinrich and cellrich fluid
Due to an increase in )essel permeability in acute inflammation
b. %!amplespneumonia, infarction, metastasis
7. ,aboratory findings distinguishing e!udates from transudates
a. "leural fluid protein/serum protein ratio abo)e 6.4
ii Indicates an e!udate
iii *ransudates ha)e )alues below 6.4.
b. "leural fluid lactate dehydrogenases/serum lactate dehydrogenase ratio abo)e 6.5
ii Indicates an e!udate
iii *ransudates ha)e )alues below 6.5.
Dpontaneous pneumothora!
;. Causes
a. Idiopathic (most common)
b. "araseptal emphysema, /arfan syndrome
2. "athogenesis
a. &upture of a subpleural or intrapleural bleb produces a hole in the pleura.
b. "leural ca)ity pressure is the same as the atmospheric pressure.
i. ,oss of the negati)e intrathoracic pressure
ii. Causes a portion of lung or the entire lung to collapse
7. Clinical findings
a. Dudden onset of dyspnea with pleuritic type of chest pain
b. "hysical e!amination
i. *ympanitic percussion note
ii. +bsent breath sounds
iii. *rachea de)iated to the side of the collapse
*ension pneumothora!
;. Causes
a. "enetrating trauma to the lungs (e.g., knife wound)
b. &upture of tension pneumatocysts (see section ?I)
2. "athogenesis
a. @laplike pleural tear allows air into the pleural ca)ity but pre)ents its e!it.
Dimilar in concept to filling a tire up with air
b. Increased pleural ca)ity pressure
c. "roduces compression atelectasis (see section I?)
7. Clinical findings
a. Dudden onset of se)ere dyspnea
b. "hysical e!amination
ii *ympanitic percussion note and absent breath sounds
iii *rachea and mediastinal structures de)iate to contralateral side.
Compromised )enous return to the heart, if the pneumothora! is located
on the left side
b. *reatment
Insert a needle into the pleural ca)ity to relie)e the pressure