Chapter 128 Pleura & Pleural Space

PLEURAL EFFUSION
osms.it/pleural-effusion

PATHOLOGY & CAUSES DIAGNOSIS

▪ Excess fluid accumulates in pleural space
▪ Lung expansion limited → impaired
ventilation
Origin
▪ Hydrothorax (serous fluid), hemothorax
(blood), urinothorax (urine), chylothorax/
lymphatic effusion (chyle), pyothorax (pus,
AKA empyema)
Pathophysiology
▪ Transudative pleural effusion
▫ Pressure driven filtration: ↑ hydrostatic
pressure/↓ oncotic pressure → force
imbalance, fluid extravasation → fluid
leaks across intact capillary membranes
▫ Alteration in Starling forces
▪ Exudative pleural effusion
▫ Local inflammatory processes → leaky
capillaries
DIAGNOSTIC IMAGING
Chest X-ray
▪ Fluid occupies space between visceral,
parietal pleural
▪ Area of whiteness on standard
posteroanterior (PA) chest X-ray
▪ Blunted costophrenic angles
▪ Greater density than rest of lung →
gravitates towards dependent regions
▫ ↑ fluid on upright X-ray or lateral
decubitus X-ray
Lung ultrasound
▪ Confirms presence of effusion and detects
pleural fluid septations

CAUSES
▪ Transudative
▫ Congestive heart failure, liver cirrhosis,
severe hypoalbuminemia, nephrotic
syndrome, acute atelectasis, myxedema,
peritoneal dialysis, Meigs syndrome,
obstructive uropathy, end-stage renal
disease
▪ Exudative
▫ Infection, malignancy, trauma,
pulmonary infarction, pulmonary
embolism, autoimmune processes,
pancreatitis, ruptured esophagus
Figure 128.1 A plan chest radiograph
demonstrating a large left sided pleural
SIGNS & SYMPTOMS effusion, in this case as a consequence
of metastatic melanoma. There is notable
▪ Asymptomatic (if small) tracheal deviation.
▪ Pleuritic chest pain
▪ Dyspnea
▫ Worse when lying down (orthopnea)

OSMOSIS.ORG 907
 ▫ Rheumatoid factor, antinuclear
antibody, complement: collagen
vascular disease
▫ Triglycerides: chylothorax from
thoracic duct leakage (trauma, cancer,
lymphoma)

OTHER DIAGNOSTICS
▪ Medical history

Figure 128.2 A CT scan of the chest in the
coronal plane demonstrating a right sided
pleural effusion.
Clinical examination
▪ ↑ fluid on affected side
▫ ↓ chest expansion
▫ Stony dullness to percussion
▫ Diminished breath sounds
▫ ↓ vocal resonance, fremitus
▫ Tracheal deviation away from effusion
▪ If lung compressed above effusion
▫ Bronchial breathing, egophony

Light’s criteria
LAB RESULTS ▪ Classification of transudative/exudative
effusion
Thoracentesis
▪ Transudative
▪ Needle inserted through chest wall, 5th–
▫ Difference between albumin in blood,
8th intercostal space, midaxillary line →
pleural fluid > 1.2g/dL
pleural space → withdraw fluid
▪ Exudative
▪ Trial diuresis for three days in heart failure
before thoracentesis ▫ Ratio of pleural fluid protein to serum
protein > 0.5
▪ Effusion analysis
▫ Ratio of pleural fluid LDH to serum LDH
▫ Amylase: pancreatitis, esophageal
> 0.6
perforation, malignancy
▫ Pleural fluid LDH > 0.6, ⅔ times lab
▫ Blood: traumatic, malignancy,
specific upper limit for serum
pulmonary embolism with infarction,
tuberculosis
▫ Cholesterol: chylous (lymphatic fluid) vs.
chyliform effusion (chyle-like fluid from
chronic disease)
▫ Cytology: malignancy, infection (reactive
effusion)
▫ Differential cell count: lymphocytic
effusion in tuberculosis, cancer,
lymphoma
▫ Glucose (low): rheumatoid arthritis,
tuberculosis, empyema, malignancy
▫ Microscopy, culture: microorganisms
▫ ↓ pH: empyema, tuberculosis,
mesothelioma Figure 128.3 The cytological appearance
▫ Protein, LDH: transudative/exudative of a benign pleural effusion. There are
numerous bland mesothelial cells mixed with
lymphocytes.

908 OSMOSIS.ORG

TREATMENT
SURGERY
▪ Therapeutic aspiration
▪ Insertion of intercostal drain
▪ Repeated effusions
▫ Surgical pleurodesis: obliteration
of pleural space; prevents fluid
accumulation
Chapter 128 Pleura & Pleural Space
OTHER INTERVENTIONS
▪ Supplemental oxygen
▪ Repeated effusions
▫ Chemical pleurodesis: obliteration
of pleural space; prevents fluid
accumulation (talc, bleomycin,
tetracycline/doxycycline)
▪ Pleural catheter
▫ User-operated daily draining
▪ Treat underlying cause
OSMOSIS.ORG 909
 PNEUMOTHORAX
osms.it/pneumothorax

PATHOLOGY & CAUSES SIGNS & SYMPTOMS

▪ Abnormal collection of air in pleural cavity ▪ Sharp chest pain (one-sided)
▪ Air enters through damage to chest wall/ ▪ Dyspnea
lung/gas-producing microorganisms ▪ Tachycardia
▫ Positive pressure in pleural space if air ▪ Cyanosis
enters → lung partial/complete collapse ▪ Hypercapnia → confusion, coma
▪ Diminished/absence of breath sounds
TYPES (affected side)
▪ Hyperresonance to percussion
Primary pneumothorax
▪ ↓ vocal, tactile fremitus
▪ No clear cause/no preexisting lung disease
▪ Trachea displaced away from affected side
▫ Secondary to ruptured blebs (small sacs
▪ Tension pneumothorax
of air on lung surface)
▫ ↓ blood pressure
Secondary pneumothorax ▫ ↓ oxygen saturation
▪ Occurs with existing lung disease ▫ Epigastric pain
▫ Displaced apex beat
Tension pneumothorax
▫ Distended neck veins
▪ One-way valve formed by damaged tissue
→ air enters, can’t escape → intrathoracic
pressure builds up → impaired cardiac,
respiratory function
DIAGNOSIS
Traumatic pneumothorax DIAGNOSTIC IMAGING
▪ Follows physical trauma to chest (e.g. blast Chest X-ray/CT scan
injury); result of medical procedure (e.g.
▪ Identifies atypical collections of gas,
iatrogenic pneumothorax)
changes in lung markings, presence of
mediastinal shift and/or tracheal deviation;
RISK FACTORS lucent/dark lung field, deep sulcus sign (a
▪ Smoking, chronic obstructive pulmonary deep costophrenic angle)
disease (COPD), asthma, tuberculosis
Ultrasound
▪ More common in individuals who are
biologically male ▪ Reverberation echoes of the pleural line,
absence of lung sliding at the pleural line
▪ Changes in atmospheric pressure
▪ Family history of pneumothoraces
OTHER DIAGNOSTICS
▪ Clinical history, physical examination

910 OSMOSIS.ORG

Figure 128.4 A CT scan of the chest in the
coronal plane demonstrating a right-sided
pneumothorax.
TREATMENT
SURGERY
Pleurodesis/pleurectomy
▪ Repeated pneumothoraces
Tension pneumothorax: needle chest
decompression
▪ AKA needle thoracostomy
▪ Emergency procedure
▪ Not definitive, improves cardiopulmonary
function
Chapter 128 Pleura & Pleural Space
▪ Large bore intravenous catheter needle
inserted into pleural space
▫ Midclavicular line: second/third
intercostal space
▫ Anterior/mid axillary line: fifth intercostal
space
▫ Listen for air escaping
▫ Remove needle, leave catheter in place
▪ May cause injury, reserve for
▫ Mechanism of injury suggestive of
pneumothorax
▫ Clinical signs of respiratory distress,
persistently low oxygen saturation
despite supplemental oxygen
▫ Hemodynamic instability
▫ Prolonged transport time
OTHER INTERVENTIONS
▪ Supplemental oxygen
▫ Improves rate of pneumothorax
reabsorption
▪ Small pneumothoraces may resolve
spontaneously
▪ If wound present, cover with dressing
▫ Dressing secured on three sides to
create “vent dressing”
▪ Chest tube (connected to water-seal
drainage system)
▫ Inserted into “safe triangle,” damage to
internal organs avoided
▫ Horizontal line, nipple to lateral
chest well; between latissimus dorsi,
pectoralis major
OSMOSIS.ORG 911

NOTES
TUBERCULOSIS
MICROBE OVERVIEW
▪ Tuberculosis (AKA Mycobacterium
tuberculosis) mycobacterium that primarily
infects lungs but may infect any bodily
organ/tissue
▪ Important properties
▫ Curved rod shaped bacteria often
wrapped together in cord-like
formations
▫ Obligate aerobe
▫ Impervious to Gram staining due to
waxy cell wall composed of fatty acids
(e.g., mycolic acid)
MYCOBACTERIUM TUBERCULOSIS
osms.it/mycobacterium-tuberculosis
PATHOLOGY & CAUSES
TYPES
Primary tuberculosis
Reactivation tuberculosis
▪ In about 5–10% cases of primary TB
Extrapulmonary tuberculosis
▪ May involve any organ (most commonly
kidneys, meninges, lymph nodes, etc.)
▪ Systemic miliary tuberculosis
STAGING
▪ Transmitted by inhaling infectious aerosol
droplets from individual with active TB (e.g.
coughing, sneezing, speaking, etc.)
▪ TB enters lungs, gets phagocytized by
macrophages → TB produces enzymes that
inhibit lysosome and phagocytic vacuole
NOTES
▫ Staining: acid-fast stains like Ziehl–
Neelsen, fluorescent stains like
auramine/rhodamine
▪ Clumped colonies
▪ Distinctly slow growing (up to 6 weeks for
visible growth)
▪ Grown on Lowenstein–Jensen media
▪ Resistant to weak disinfectants, can survive
on dry surfaces for months
▪ Can avoid mucus traps, getting into deep
airways (alveoli)
fusion → bacteria survives, proliferates,
creates localized infection → primary
tuberculosis development
▫ TB infiltrated macrophage fusion →
Langhans giant cells
▫ Cell-mediated immunity activation →
granuloma forms within infected area →
caseous necrosis inside granuloma →
Ghon focus
▫ Lymphatic dissemination of TB → lymph
node caseation
▫ Ghon focus + involved lymph node →
Ghon complex
▫ Ghon complex fibrosis, calcification →
Ranke complex
▪ Primary infection resolution
▫ Mycobacteria killed by immune system
▫ Bacteria walled off in granuloma
remains dormant but viable →
latent tuberculosis with no further
complications in immunocompetent
OSMOSIS.ORG 583
 individuals
▪ Compromised immune system → more
caseous necrosis areas → cavity formation
→ reactivation tuberculosis

RISK FACTORS
▪ Immunocompromised states
▫ HIV
▫ Diabetes mellitus
▫ Hematologic malignancy
▫ Chronic lung disease (especially
silicosis)
▫ Malnutrition
▫ Aging
▪ Substance abuse
▫ Alcoholism Figure 105.1 The gross pathological
▫ Injection drug users appearance of a Ghon focus.
▪ Close contact with individuals with active
TB infection
▫ Healthcare providers
SIGNS & SYMPTOMS
▫ Incarceration
▪ Lower-income, medically underprivileged ▪ Primary tuberculosis
countries
▫ Usually asymptomatic (90-95% of
▫ Recent immigrants from high- cases)
prevalence countries
▫ Mild flu-like illness
▫ Rarely pleural effusion
COMPLICATIONS ▪ Reactivation tuberculosis
▪ Bronchopneumonia ▫ Constitutional symptoms (fever, chills,
▪ Pneumothorax night sweats, fatigue, appetite loss,
▪ Extrapulmonary tuberculosis weight loss, pleuritic chest pain)
▫ Kidney → dysuria, pyelonephritis with ▫ Cough (dry cough, prolonged
sterile pyuria cough producing purulent sputum,
▫ Meninge → meningitis hemoptysis—suggesting advanced TB)
▫ Lumbar vertebrae → Pott disease ▫ Crepitations during lung auscultation
▫ Liver and gallbladder → hepatitis, ▪ Extrapulmonary tuberculosis
obstructive jaundice ▫ Depending on affected organ/tissue
▫ Lymph nodes → cervical tuberculous ▪ Miliary (disseminated) tuberculosis
lymphadenitis (scrofula) ▫ Can affect any organ (e.g. choroidal
▫ Peritonitis tubercles in eye, granulomas within
▫ Pericarditis organs)
▪ Systemic infection ▫ Weight loss
▫ Fever, chills
▫ Dyspnea

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 Chapter 105 Tuberculosis

Antibiotic resistance
DIAGNOSIS ▪ Multiple-drug-resistant TB
▫ Resistant to isoniazid and rifampin
DIAGNOSTIC IMAGING ▪ Extensively drug-resistant TB
▫ Resistant to both isoniazid and rifampin,
Chest X-ray
any fluoroquinolone, at least one
▪ Used in PPD/IGRAs positive second-line drug
▪ Ranke complex → sign of healed primary
TB
▪ Cavities → active TB sign

LAB RESULTS
PPD intradermal skin test (tuberculin test)
▪ Screening test for people at high risk for TB
▫ Tuberculin injection between dermal
layers, induration area measurement
within 48–72 hours
▪ Induration area ≥ 5mm: positive in
immunocompromised individuals, persons
with primary TB radiographic evidence/
close contact with those with active TB
▪ Induration area ≥ 10mm: positive in
residents/immigrants from high-prevalence
countries, children > four years of age, high Figure 105.2 An X-ray image of the chest
risk populations (e.g., medical employees) demonstrating diffuse interstitial granular
▪ Induration area ≥ 15mm: considered densities in an individual with milliary
positive in individuals with no known risk tuberculosis.
factors
▪ Cannot be used for differentiation between
active and latent TB
▪ PPD result interpretation
▫ Positive → exposure evidence
▫ False-positive → previously immunized
with BCG vaccine
▫ Negative → no exposure evidence
▫ False-negative → sometimes seen
in individuals with sarcoidosis,
malnutrition, Hodgkin’s lymphoma

Sputum testing
▪ Used for definitive diagnosis
▪ Staining, culture, PCR

OTHER DIAGNOSTICS
Interferon gamma release assays (IGRAs)
▪ Alternative for PPD
▪ Unlike PPD, doesn’t show false-positive
results in BCG vaccinated
Figure 105.3 Multifocal patchy opacities
in the right upper lobe of an individual who
presented with night sweats, weight loss and
persistent cough. The presenting symptoms
and radiological appearance are consistent
with pulmonary tuberculosis.

OSMOSIS.ORG 585
 TREATMENT
MEDICATIONS
▪ Prophylactics
▫ BCG vaccine (some countries)
▪ Latent TB
▫ Isoniazid for 9 months
▪ Active TB
▫ First line anti-TB drugs: isoniazid,
rifampin, pyrazinamide, ethambutol/
streptomycin
▪ Antibiotic resistance
Figure 105.4 The histological appearance
▫ For multiple-drug-resistant TB, of a tuberculosis granuloma. The granuloma
treatment requires second-line drugs is formed of epithelioid macrophages and
(amikacin, kanamycin, capreomycin) giant cells with a focus of caseating necrosis
at the centre and a rim of lymphocytes at the
OTHER INTERVENTIONS periphery.
▪ Active TB
▫ Compulsory isolation (until sputum
negative for TB)

586 OSMOSIS.ORG
 NOTES

NOTES
LOWER RESPIRATORY TRACT
INFECTION

GENERALLY, WHAT IS IT?

PATHOLOGY & CAUSES DIAGNOSIS
▪ Infections involving trachea, bronchi, LAB RESULTS
bronchioles, lungs ▪ Complete blood count (CBC)

Microbe identification
RISK FACTORS ▪ Blood culture, sputum culture; Gram stain,
▪ Smoking, compromised immunity, age polymerase chain reaction (PCR)
(children, elderly), comorbidities

COMPLICATIONS TREATMENT
▪ Respiratory compromise, infection spread,
sepsis MEDICATIONS
▪ Antimicrobials

SIGNS & SYMPTOMS OTHER INTERVENTIONS

▪ Ventilatory support
▪ Cough, dyspnea, fatigue, fever

BACTERIAL TRACHEITIS
osms.it/bacterial_tracheitis
RISK FACTORS
PATHOLOGY & CAUSES ▪ Antecedent viral infections, especially croup
▪ Commonly affects children
▪ Rare, potentially life-threatening exudative
infection
▫ Characterized by mucosal ulceration, COMPLICATIONS
pseudomembrane formation, airway ▪ Pneumonia, septicemia, pneumothorax,
obstruction risk (due to edema, pneumomediastinum, hypoxia (secondary
exudative sloughing) to airway obstruction), cardiorespiratory
▪ Common infective agents: Staphylococcus arrest
aureus, Moraxella catarrhalis, Streptococcus
pneumoniae, H. influenzae

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 Chapter 125 Lower Respiratory Tract Infections

SIGNS & SYMPTOMS TREATMENT

▪ Prodromal respiratory viral infection MEDICATIONS
presentation → acute onset of fever, ▪ Broad antibiotic coverage
hoarseness, sore throat, stridor
▪ Productive, barky cough with copious
OTHER INTERVENTIONS
tracheal secretions, retrosternal pain
▪ Ventilatory support
▪ Progressive respiratory distress
▫ Humidified supplemental oxygen,
▫ Dyspnea, retractions, fatigue, ↓ level of
intubation, endoscopic tracheal
consciousness
debridement
▪ Fluid management
DIAGNOSIS
DIAGNOSTIC IMAGING
Chest X-ray
▪ Upper tracheal narrowing (“steeple sign”)
▪ Tracheal pseudomembranes (irregular
shadows)

LAB RESULTS
▪ CBC: leukocytosis, left shift

Microbe identification
▪ Positive tracheal culture, Gram stain

OTHER DIAGNOSTICS
▪ Laryngoscopy: subglottic edema; tracheal
lumen narrowing; presence grayish
exudate; slough, pus; friable tracheal Figure 125.1 The endoscopic appearance of
mucosa bacterial tracheitis in a nine-year-old boy.

BRONCHIOLITIS
osms.it/bronchiolitis
PATHOLOGY & CAUSES
▪ Viral small airway respiratory infection
▪ Viral spread through respiratory secretions,
contaminated hands → infects lower
respiratory tract cells → natural killer cells
attack → cytokines released → epithelial
cells produce mucus, vessels vasodilate →
fluid leaks, walls swell → airway narrows
(more severe in children)
▪ Dead cells, mucus slide into airway → form
mucus plugs → trap air → airways collapse
(atelectasis)
CAUSES
▪ Respiratory syncytial virus (RSV): most
common, especially during winter months
▪ Adenovirus, human bocavirus, human
metapneumovirus
▪ Mycoplasma pneumoniae

OSMOSIS.ORG 879
 RISK FACTORS
▪ Young age (children < two years old),
previous infection, daycare attendance,
decreased immunity, neuromuscular
disorders, premature birth, cardiovascular
malformations, airway malformations,
exposure to smoking

COMPLICATIONS
▪ Hypoxemia, sepsis

SIGNS & SYMPTOMS

▪ Congestion, pharyngitis, sore throat, cough
▪ Hypoxia → tachycardia, tachypnea,
exhaustion Figure 125.2 A plain chest radiograph in
▪ If severe: dyspnea, wheezing, central apnea a child with bronchiolitis demonstrating
(brief periodic breathing arrest), nasal bilateral hilar fullness.
flaring, retractions, cyanosis, fever, poor
feeding, ↓ activity

DIAGNOSIS
DIAGNOSTIC IMAGING
X-ray
▪ Patchy infiltrates, atelectasis

LAB RESULTS
▪ Positive rapid viral testing (RT-PCR):
suggests viral infection

TREATMENT
OTHER INTERVENTIONS
Figure 125.3 A CT scan of the chest in
Immunoprophylaxis the axial plane in an individual with severe
▪ Palivizumab: monoclonal antibody against bronchiolitis. Both lung fields demonstrate
RSV given monthly throughout RSV season the tree-in-bud pattern.
for prematurely-born infants, chronic lung
disease, congenital heart disease
▪ Heated, humidified supplemental oxygen
(high-flow nasal cannula/continuous
positive airway pressure (CPAP)), fluids,
nasal suctioning
▪ Intubation (if hypoxia continues despite
intervention)

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 Chapter 125 Lower Respiratory Tract Infections

COMMUNITY–ACQUIRED
PNEUMONIA
osms.it/community-acquired_pneumonia
Resolution
PATHOLOGY & CAUSES ▪ Approx. day 8, can continue for three
weeks
▪ Pneumonia acquired outside hospital/
▫ Exudate digested by enzymes, ingested
healthcare setting
by macrophages, coughed up
▪ Viral pneumonia may → superimposed
bacterial infection
COMPLICATIONS
Spread ▪ Meningitis, sepsis, pleural effusions
▪ Respiratory: from host to host
▪ Hematogenous: from another infection with
same pathogen (e.g. cellulitis) SIGNS & SYMPTOMS
Causative organisms ▪ High fever, cough, hemoptysis, pleuritic
▪ S. pneumoniae, S. aureus, H. influenzae, chest pain, tachypnea, tachycardia,
group A streptococci, influenza virus, dyspnea, muscle pain, fatigue
respiratory syncytial virus (RSV), ▪ Crepitation on palpation, dullness on
parainfluenza percussion

RISK FACTORS
▪ Advanced age, lowered immunity, smoking,
alcohol abuse, malnutrition, chronic lung
disease

STAGING
Congestion
▪ Between days 1–2
▫ Blood vessels, alveoli start filling with
excess fluid

Red hepatization
▪ Between days 3–4
▫ Exudate (contains red blood cells,
neutrophils, fibrin) starts filling airspaces
→ solidifies them → lungs develop liver-
like appearance
Figure 125.4 A plain chest radiograph
Gray hepatization demonstrating patchy peri-bronchial
shadowing in an individual with
▪ Approx. days 5–7
bronchopneumonia.
▫ Lungs remain firm but color changes →
red blood cells in exudate start to break
down

OSMOSIS.ORG 881
 Prevention
DIAGNOSIS ▪ 23-valent vaccine (Pneumovax) available
against pneumococcus
DIAGNOSTIC IMAGING
▫ Recommended in splenectomised,
X-ray immunocompromised individuals
▪ Interstitial infiltrates; consolidation; may
show pleural effusion

LAB RESULTS
▪ ↓ oxygen saturation
▪ CBC: leukocytosis
▪ Organism identification: sputum Gram
stain, culture; C-reactive protein test (CRP),
PCR for typical viruses
▪ Positive urine for S. pneumoniae

TREATMENT
MEDICATIONS
▪ Antibiotics

OTHER INTERVENTIONS Figure 125.5 A plain chest radiograph

▪ Supplemental oxygen, fluids demonstrating consolidation of the right
middle lobe in an individal with lobar
pneumonia.

882 OSMOSIS.ORG
 Chapter 125 Lower Respiratory Tract Infections

Figure 125.6 The histological appearance

of acute pneumonia. In the affected part
of the lung (right) the alveoli are filled with
neutrophils.

CROUP
osms.it/croup

PATHOLOGY & CAUSES SIGNS & SYMPTOMS

▪ Acute respiratory condition ▪ Progressive respiratory symptoms; sore
▫ Characterized by laryngotracheitis throat, hoarse voice (due to laryngeal
▪ Immune response to epithelial viral infection involvement)
▫ Upper bronchi: larynx, trachea narrow ▪ Respiratory symptoms
due to swelling ▫ “barking” cough
▫ Lower bronchi: terminal bronchioles, ▫ Tachypnea
viral pneumonia ▫ Grunting (attempt to increase end-
expiratory pressure)
CAUSES ▫ Prominent inhalation, inspiratory stridor,
apnea
▪ RSV, parainfluenza, adenoviruses
▪ Historically: Corynebacterium diphtheriae
(vaccine development → ↓ incidence) DIAGNOSIS
RISK FACTORS DIAGNOSTIC IMAGING
▪ Most common in children < six years old X-ray
▪ “Steeple sign,” narrowing below epiglottis
COMPLICATIONS
▪ Hypoxia, respiratory failure LAB RESULTS
▪ Secondary bacterial infections → ↑ ▪ CBC: normal ↑ with left shift, or ↓
mortality

OSMOSIS.ORG 883
 OTHER DIAGNOSTICS
▪ Severity: Westley scale 0–17
▫ 3-7: moderate
▫ 8-11: severe
▫ 12 and above: indicates respiratory
failure

TREATMENT
MEDICATIONS
▪ Dexamethasone, epinephrine (nebulized)

OTHER INTERVENTIONS
▪ Humidified supplemental oxygen, fluids,
antipyretics
▪ Intubation (if impending respiratory failure) Figure 125.7 A plain X-ray image
demonstrating the steeple sign in an infant
with croup.

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 Chapter 125 Lower Respiratory Tract Infections

NOSOCOMIAL PNEUMONIA
osms.it/nosocomial-pneumonia

PATHOLOGY & CAUSES SIGNS & SYMPTOMS

▪ Hospital-acquired pneumonia ▪ Nonspecific symptoms (malaise, lethargy),
▫ AKA healthcare-associated pneumonia fever, productive cough
▫ Includes ventilator-associated
pneumonia
DIAGNOSIS
▪ Involves microaspiration of organisms
from oropharyngeal tract/sometimes from
DIAGNOSTIC IMAGING
gastrointestinal tract
▪ Severity varies depending on offending Chest X-ray
organism, individual’s immune system ▪ Shows infiltrates
status

LAB RESULTS
CAUSES ▪ CBC: leukocytosis, ↑ CRP
▪ MRSA, Klebsiella pneumoniae, ▪ Positive sputum culture
Pseudomonas aeruginosa, Acinetobacter
▪ Often polymicrobial
TREATMENT
RISK FACTORS
▪ Intubation, poor staff hygiene, MEDICATIONS
contaminated equipment contact ▪ Antibiotics

COMPLICATIONS OTHER INTERVENTIONS

▪ Meningitis, sepsis, pleural effusions ▪ Supplemental oxygen, fluids

OSMOSIS.ORG 885
 NOTES

NOTES
RESPIRATORY TUMORS

GENERALLY, WHAT ARE THEY?

RISK FACTORS
PATHOLOGY & CAUSES ▪ Age
▫ Malignancy more common in older
▪ Uncontrolled division of epithelial cells
individuals
lining respiratory tract → formation of solid
tumor ▪ Smoking
▪ Mutated cells become cancerous ▫ Direct, linear positive correlation
between pack years, risk of lung cancer
▫ Resist inhibitory signals, evade immune
surveillance ▪ Asbestos exposure, radon exposure,
ionizing radiation exposure
▪ Malignant tumors invade basement
membrane ▪ Chronic obstructive pulmonary disease
(COPD)
▫ Carcinoma in situ
▪ Tuberculosis
▪ Metastasis
▫ Malignant tumors establish secondary
tumors at distant site; lung cancer MNEMONIC: ABCDE
metastasizes quickly
Presentation of lung cancers
▫ Common sites: mediastinum, hilar
Bronchial Airway disruption →
lymph nodes, lung pleura, breasts, liver,
pneumonia
adrenal glands, brain, bones
Blood: hemoptysis
Cough
TYPES Distribution: mestastasis
Small-cell whEEzing
▪ Small, immature, neuroendocrine cells;
divide rapidly, spread quickly

Non-small-cell (most common) SIGNS & SYMPTOMS

▪ Large cells; divide, spread slowly
▪ Asymptomatic in early disease
▫ Adenocarcinoma (goblet cells)
▪ Nonspecific, wide overlap with other
▫ Squamous cell carcinoma (squamous
noncancerous lung conditions
cells)
▪ Constitutional symptoms: loss of appetite,
▫ Large cell carcinoma
weight loss, weakness
▫ Carcinoid tumors (mature
▪ If located in certain areas (e.g. upper lobe of
neuroendocrine cells)
lung) → compressive symptoms
Nonspecific classification ▫ Nerve compression: hoarseness
▪ Small-cell carcinoma with poorer prognosis (recurrent laryngeal nerve), Horner’s
syndrome (sympathetic chain),
diaphragmatic paralysis (phrenic nerve)
▪ Paraneoplastic syndromes
▫ Digital clubbing, muscle weakness,
syndrome of inappropriate antidiuretic

OSMOSIS.ORG 923
 hormone secretion (SIADH), ectopic
adrenocorticotropic hormone (ACTH)
secretion, ectopic parathyroid hormone
(PTH)-like secretion, hypertrophic
pulmonary osteoarthropathy, Eaton–
Lambert syndrome
▫ Mostly small cell carcinoma
(neuroendocrine cells secrete hormones
with systemic effects)
DIAGNOSIS
DIAGNOSTIC IMAGING
Chest X-ray
▪ Coin lesion
CT scan
▪ Asymmetrical, expanding nodule; used
for staging; can demonstrate extent
of metastasis (e.g. hilar lymph node
involvement)
PET
▪ Areas of higher glucose turnover
▪ Bronchoscope
▪ Diagnosis of central (near to main
bronchus) tumors, not peripheral tumors
MESOTHELIOMA
osms.it/mesothelioma
PATHOLOGY & CAUSES
▪ Cancer of mesothelium; most commonly
lungs, chest wall pleural lining (composed
of mesothelial cells); sometimes
pericardium
▪ Commonly associated with asbestos
exposure
▪ Asbestos fibers
▫ Mineral used as construction, insulation
material
▫ Jagged in shape, very fine
▫ Increases risk of lung cancer, malignant
mesothelioma
924 OSMOSIS.ORG
LAB RESULTS
▪ Sputum sample
▫ Diagnosis of central (near to main
bronchus) tumors, not peripheral tumors
▪ Fine needle aspiration
▫ Histopathologic diagnosis using
cytology
▪ Endoscopic biopsy
TREATMENT
MEDICATIONS
▪ Simple analgesics, opioids (if severe)
▫ Pain management
SURGERY
▪ Intraoperative frozen section if diagnosis of
malignancy uncertain
▪ If malignancy confirmed, wedge resection
performed for small tumors
▪ Lobectomy performed for larger tumors/
after wedge resection if margins positive
OTHER INTERVENTIONS
▪ Chemotherapy, immunotherapy, radiation
therapy
▪ Asbestos fibers inhaled → phagocytic cells
attempt to phagocytose fibers → unable to
destroy fibers → apoptosis of phagocytic
cells → release of tumor promoting factors
→ mesothelial cells of pleura inflamed →
DNA damage → mesothelial cells divide
uncontrollably → tumor formation
▪ Mesothelial plaques cover visceral, parietal
pleura; extend around chest cavity
▪ Asbestos fibers can be found in stomach
(via swallowing of saliva/mucus containing
asbestos)
▪ Mesothelioma can theoretically affect
any organ with mesothelial cells, most
commonly found in thoracic cavity
 Chapter 130 Respiratory Tumors

TYPES
TREATMENT
Malignant
▪ Prognosis is poor, unless caught early; MEDICATIONS
extremely resistant to treatment; spread to ▪ Chemotherapy
multiple organs

Benign SURGERY
▪ Prognosis is excellent; surgery for isolated ▪ Excision
lesions usually curative
OTHER INTERVENTIONS
▪ Radiation
SIGNS & SYMPTOMS
▪ Angina, dyspnea, recurrent pleural
effusions, weight loss, cough
▪ If tumor invades blood vessel
▫ Blood-tinged sputum

DIAGNOSIS
DIAGNOSTIC IMAGING
Chest X-ray, CT scan
▪ Visualize mesothelioma lesions

LAB RESULTS
Biopsy
▪ Video assisted thoracoscopic surgery
(VATS) Figure 130.1 A CT scan of the chest in the
▪ Tissue sample immunostained with coronal plane demonstrating a mesothelioma
antibody that reacts to calretinin occupying the lower thoracic cavity.
▫ Calretinin: calcium-binding protein that
regulates calcium levels inside cells
▫ Distinguishes mesotheliomas from other
tumors
▪ Cancerous cells have “fried egg”
appearance

Figure 130.2 Immunohistochemical staining

with calretinin reveals the architecture of this
pleural mesothelioma.

OSMOSIS.ORG 925
 Figure 130.3 The histological appearance
of epithelioid mesothelioma. The malignant
cells are cuboidal, have moderate amounts of
cytoplasm and display conspicuous nucleoli.

Figure 130.4 The gross pathology of a large

mesothelioma of the thoracic cavity. The
tumor completely encases the normal lung
tissue (outlined).

NASOPHARYNGEAL CARCINOMA
osms.it/nasopharyngeal-carcinoma
MNEMONIC:
PATHOLOGY & CAUSES NASOPharyngeal
Types of Nasopharyngeal
▪ Cancer of nasopharynx (upper throat, malignant cancers
behind nose)
Nasopharyngeal
▪ Most common malignant tumor of
Adenocarcinoma
nasopharynx
Squamous cell carcinoma
▪ Can be clinically silent for long periods,
difficult to detect early Olfactory neuroblastoma
▪ Often metastasizes to cervical lymph nodes Plasmacytoma
▪ Associated with Epstein–Barr virus (EBV)
▪ Prognosis
Undifferentiated/basaloid carcinoma
▫ Five year survival rate, 60% (all types) (lymphoepithelioma)
▪ Most radiosensitive
TYPES
Keratinized squamous cell carcinoma RISK FACTORS
▪ Worst prognosis, least radiosensitive ▪ More common in individuals who are
biologically male, < 55 years
Nonkeratinized squamous cell carcinoma ▪ Family history
▪ Best prognosis ▪ Common in Asia, Africa (esp. children); in
southern China, common in adults, rare in
children

926 OSMOSIS.ORG
 Chapter 130 Respiratory Tumors

▪ Diets high in nitrosamines (fermented

foods), alcohol TREATMENT
▪ Smoking, certain chemical fumes,
formaldehyde
MEDICATIONS
▪ Monoclonal antibodies
▫ Synthetic antibodies, target epidermal
COMPLICATIONS growth factor receptors (EGFRs);
▪ Radiation adverse effects (Type III hypersensitivity
▫ Death of healthy tissue, brain stem infusion reaction, rash, fatigue,
injury, blindness, xerostomia headache, fever, diarrhea)

SIGNS & SYMPTOMS SURGERY

▪ Surgical resection
▪ Altered vision, recurrent ear infections,
headache, tinnitus, nosebleeds, sore throat, OTHER INTERVENTIONS
facial paresthesia ▪ Intensity-modulated radiation therapy
▪ Lump in neck, epistaxis, nasal obstruction (standard)
▫ High-precision radiation, minimizes
damage to surrounding tissues; better
DIAGNOSIS outcome, less adverse effects than
conventional radiation therapy
DIAGNOSTIC IMAGING
CT scan, MRI, PET, X-ray, nasopharyngos-
copy/nasal endoscopy
▪ Visualize carcinoma

LAB RESULTS
Biopsy
▪ Squamous cell carcinoma/undifferentiated

OTHER DIAGNOSTICS
▪ Physical exam
▫ Neck swelling

Figure 130.5 An MRI scan of the head in

the sagittal plane demonstrating a large
nasopharyngeal carcinoma blocking the
choanae and invading the skull base.

OSMOSIS.ORG 927
 NON-SMALL-CELL LUNG
CARCINOMA
osms.it/nsclc

PATHOLOGY & CAUSES DIAGNOSIS

▪ Lung cancers not of small-cell type LAB RESULTS
▪ Grow, spread more slowly
Fine needle aspiration (lung)
▪ Cells demonstrate cardinal features of
TYPES malignancy
▫ Variation in nuclear size, shape;
Squamous-cell carcinoma
irregularly distributed nuclear chromatin;
▪ Centrally located, strongly associated with large prominent nucleoli
smoking

Adenocarcinoma
▪ Develops peripherally in bronchiole/alveolar
TREATMENT
sac, no link to smoking
SURGERY
Large-cell carcinomas ▪ Contraindicated in cases of metastasis
▪ Found throughout lungs; centrally, outside of chest
peripherally ▪ Recurrence likely even after complete
▪ Diagnosis of exclusion; if criteria for resection
adenocarcinoma/squamous-cell carcinoma
not met OTHER INTERVENTIONS
Bronchial carcinoid tumor ▪ Radiation, chemotherapy
▪ Low-grade malignancy of neuroendocrine
cells
▪ Same cell of origin as small-cell carcinoma;
malignant potential low

SIGNS & SYMPTOMS

▪ Cough
▪ Hemoptysis
▪ Hoarseness
▪ Chest pain
▪ Weight loss
Figure 130.6 A cytological preparation of
▪ Neurologic symptoms (brain metastasis is
a bronchial washing containing malignant
common)
squamous cells.

928 OSMOSIS.ORG
 Chapter 130 Respiratory Tumors

Figure 130.8 The histological appearance

of squamous cell carcinoma of the lung.
The tumor cells have large amounts of
eosinophilic cytoplasm, have irregular nuclear
forms and are forming islets. The surrounding
lung demonstrates a chronic inflammatory
cell reaction.

Figure 130.7 The gross pathological

appearance of squamous cell carcinoma of
the lung. There is a large primary tumor in the
upper lobe with intrapulmonary metastases
in the lower lobe.

Figure 130.9 The histological appearance

of adenocarcinoma of the lung. The tumor is
forming slit like spaces called acini, which are
lined by malignant cells.

OSMOSIS.ORG 929
 PANCOAST TUMOR
osms.it/pancoast-tumor
▫ Brachial plexus: ipsilateral paresthesia
PATHOLOGY & CAUSES
▫ Laryngeal nerves: voice hoarseness
▪ Pulmonary neoplasm located in lung apices ▫ SVC: SVC syndrome (facial flushing,
edema, dyspnea)
▪ Location enables them to impinge nerves,
vessels
▪ Majority DIAGNOSIS
▫ Non-small-cell lung tumors
(adenocarcinoma/squamous cell DIAGNOSTIC IMAGING
carcinoma)
▪ Structures most vulnerable to compression/ CT scan/chest X-ray
invasion ▪ Tumor in lung apex
▫ Cervical sympathetic nerves, brachial
plexus, laryngeal nerves, superior vena LAB RESULTS
cava (SVC)
Biopsy
▪ Confirm tumor type
MNEMONIC: Horner has a
MAP of the Coast
OTHER DIAGNOSTICS
PanCoast → Horner’s
syndrome, including: ▪ Physical examination
Miosis
Anhidrosis TREATMENT
Ptosis
▪ Impingement of important nerve /vessel;
shrink tumor before resection
SIGNS & SYMPTOMS
MEDICATIONS
▪ Cough, angina, dyspnea, hemoptysis, ▪ Chemotherapy
wheezing ▫ Late stages: chemotherapy alone;
▪ Recurrent pneumonia prophylactic radiation to decrease
▪ Constitutional symptoms chance of brain metastases
▫ Loss of appetite, weight loss, weakness
SURGERY
Local inflammation and compression
▪ Surgical resection
▪ Tumor causes local inflammation,
invasion of nearby nerves/vessels, direct
compression OTHER INTERVENTIONS
▪ Pain, upper extremity weakness due to ▪ Radiation
brachial plexus impingement ▫ Early stages: used with chemotherapy
▪ Compression
▫ Cervical sympathetic nerves: Ipsilateral
Horner syndrome (ptosis, miosis,
anhidrosis)

930 OSMOSIS.ORG

Figure 130.10 The gross pathological
appearance of squamous cell carcinoma of
the lung. There is a large primary tumor in the
upper lobe with intrapulmonary metastases
in the lower lobe.
SMALL-CELL LUNG CANCER
osms.it/sclc
PATHOLOGY & CAUSES
▪ Uncontrolled proliferation of small,
immature, neuroendocrine cells
▪ Strongly associated with smoking
▪ Usually develops centrally in lung, near
main bronchus
▪ Grows fastest, rapidly metastasizes to
other organs; intrapulmonary metastasis
also common
▪ Secretes hormones → paraneoplastic
syndromes
▫ Cushing’s syndrome: excretion of
cortisol from adrenal glands → elevated
blood glucose, high blood pressure
▫ SIADH: release of antidiuretic hormone
(ADH) from tumor → water retention
→ high blood pressure, edema,
concentrated urine
▫ Eaton–Lambert myasthenic syndrome
(Type II hypersensitivity): small-cell
Chapter 130 Respiratory Tumors
Figure 130.11 A CT scan of the chest in the
coronal plane demonstrating a pancoast
tumor at the apex of the right lung.
carcinoma stimulates production of
autoantibodies → destroy neurons
TYPES
Limited
▪ Contained within one lung, supraclavicular
nodes (no extension to cervical/axillary
nodes)
▪ Prognosis
▫ Five year survival, 10% (median survival
15–20 months)
Extensive
▪ Spreads beyond one lung, supraclavicular
nodes
▪ Prognosis
▫ Five year survival, 1% (median survival
8–13 months)
OSMOSIS.ORG 931
 SIGNS & SYMPTOMS
▪ Dyspnea
▪ Wheezing
▪ Cough
▪ Hemoptysis

DIAGNOSIS
LAB RESULTS
▪ Histology Figure 130.12 The histological appearance of
small cell carcinoma. The cells have minimal
▫ Large cells with limited cytoplasm,
cytoplasm and moulded nuclei.
nuclear moulding

TREATMENT
SURGERY
▪ Usually not curative

OTHER INTERVENTIONS
▪ Limited
▫ Combination of chemotherapy, radiation
therapy
▪ Extensive
▫ Chemotherapy, prophylactic radiation

Figure 130.13 A PET-CT scan in the coronal

plane demonstrating high-uptake in the left
upper lobe, corresponding with a small cell
carcinoma of the lung. The left ventricle also
demonstrates high uptake, but this is normal.

Figure 130.14 A cytology specimen

demonstrating the characteristic features
of small cell carcinoma; nuclear moulding,
salt and pepper chromatin and minimal
cytoplasm.

932 OSMOSIS.ORG

SUPERIOR VENA CAVA SYNDROME
osms.it/svc-syndrome
PATHOLOGY & CAUSES
▪ Constellation of signs, symptoms when
blood flow through SVC obstructed
▪ Obstruction → increase in venous pressure
behind obstruction → blood rerouted
through collateral vessels → blood drains
into inferior vena cava, right atrium →
dilation of collateral veins → venous
pressure decreases with full dilation of
collateral veins
▪ Collateral vessels
▫ Azygos vein, internal mammary vein,
lateral thoracic vein, esophageal venous
systems
CAUSES
▪ Obstruction (external/internal)
▫ Tumor invasion, mass effect
(inflammation, swelling)
▫ Lung cancer most common (e.g.
Pancoast tumor), tumor of lymph nodes
(e.g. lymphomas)
▫ Blood clot (develops in individuals with
long-term device; e.g. indwelling central
venous catheter)
COMPLICATIONS
▪ Edema, dysphagia, cerebral ischemia
▪ Severe cerebral edema → compression of
blood vessels in brain → cerebral ischemia
Chapter 130 Respiratory Tumors
SIGNS & SYMPTOMS
▪ Edema of face, neck; inspiratory stridor;
voice changes; flushed appearance (backup
of blood, venous stasis); dilated neck,
chest veins; dyspnea (blockage of SVC
→ decreased return of blood to heart →
less blood pumped to lungs); hoarseness
of voice (compression of laryngeal nerve/
muscles of larynx from excess fluid)
DIAGNOSIS
DIAGNOSTIC IMAGING
Chest X-ray/CT scan/venous angiography
▪ Visualize tumors, collateral vessel dilation,
obstruction
LAB RESULTS
Biopsy
▪ Evaluate tumor; determine type, staging
TREATMENT
MEDICATIONS
▪ Steroids
▫ Reduce swelling around tumor
▪ Anticoagulants
▫ Treat blood clot
OTHER INTERVENTIONS
▪ Combination of surgery, chemotherapy,
radiation therapy
▪ Keep head above level of heart to help
drain fluid from head, neck to heart
OSMOSIS.ORG 933
934 OSMOSIS.ORG
 NOTES

NOTES
VENOUS DYSFUNCTION

GENERALLY, WHAT IS IT?

▪ Localized hyperpigmentation/skin
PATHOLOGY & CAUSES discoloration
▪ Hard, cord-like veins/prominent dilated
▪ Venous system defects affecting blood flow
tortuous veins
from lower extremities

CAUSES DIAGNOSIS
▪ Blood clot partially/completely blocking
way/venous valves failing to pump blood DIAGNOSTIC IMAGING
against gravity Doppler ultrasound
Virchow’s triad ▪ Assess vein diameter, thrombi, valve status,
▪ Hypercoagulability, increased clot formation blood flow (anterograde vs. retrograde)
▫ Factor V Leiden thrombophilia Venography
▫ Protein C and protein C deficiencies ▪ X-ray, contrast medium injected into vein
▪ Venous stasis from prolonged ▪ Assess status of vein network, detect
immobilization (e.g. bed rest) thrombi
▪ Damage to endothelial lining
LAB RESULTS
RISK FACTORS ▪ D-Dimer: High sensitivity (~100%) and
▪ Prolonged immobility, hereditary clotting negative predictive value (~100%) for
dysfunctions, high estrogen levels, obesity detection of venous thromboembolism
▪ One venous dysfunction can lead to
another
TREATMENT
MNEMONIC: PHD MEDICATIONS
Virchow's Triad ▪ Acute manifestation: unfractionated
Prolonged immobilization heparin/low-molecular-weight heparins
(stasis) ▪ Long-term management: oral
Hypercoagulability anticoagulants (e.g. warfarin)
Damage to endothelium ▪ Prior DVT
▫ Long term anticoagulation therapy,
antiplatelet treatment, parenteral
anticoagulants
SIGNS & SYMPTOMS
▪ Localized pain, usually lower extremities
SURGERY
▪ Vein transplant/repair/removal
▪ Edema
▪ Pruritus

176 OSMOSIS.ORG

OTHER INTERVENTIONS
▪ Preventative: calf exercises, compression
stockings/devices, raise affected areas to
decrease swelling
CHRONIC VENOUS INSUFFICIENCY
(CVI)
osms.it/chronic-venous-insufficiency
PATHOLOGY & CAUSES
▪ Veins cannot push blood back to heart,
resulting in blood pooling in leg
CAUSES
▪ Develops from varicosities, DVT, phlebitis
▫ Varicose veins affect superficial veins,
but blood sometimes rerouted to
collateral veins deep in leg, preventing
blood stagnation
▪ When deep veins carry more blood than
normal
▫ Deep veins stretch over time, blood
pools
▫ Blood flow stagnation in lower
extremities causes inflammatory
reaction in vessels, tissue, causing
fibrosis, venous stasis ulcers
RISK FACTORS
▪ Biological females, inactive standing/sitting
for long periods, aging, family history,
ligamentous laxity, obesity, smoking, low-
extremity trauma, prior venous thrombosis,
arteriovenous shunt, pregnancy
SIGNS & SYMPTOMS
▪ Calf/ankle pain (most common symptom)
▪ Worse with prolonged standing/sitting,
improves with leg elevation, movement
▪ Brown hyperpigmentation of skin
Chapter 26 Venous Dysfunction
(hemosiderin deposits)
▪ Pruritus, stasis dermatitis
▪ Painless, wet ulcers, particularly on medial
malleolus
▪ Edema
▪ Atrophie blanche: hypopigmented atrophic
areas with telangiectasia (clusters of red/
purple capillaries), red dots
DIAGNOSIS
DIAGNOSTIC IMAGING
Doppler ultrasound imaging
▪ Most common diagnostic
▪ Modified vein diameter (increased = acute
thrombus, decreased = chronic thrombus)
▪ Absent color flow: vein completely
occluded
▪ Increased flow in surrounding superficial
veins
Venography
▪ Most effective, but invasive and cost-
prohibitive
TREATMENT
SURGERY
▪ Vein transplant/repair/removal
OTHER INTERVENTIONS
▪ Preventative: calf exercises, compression
stockings/devices, raise affected areas to
decrease swelling
OSMOSIS.ORG 177
 Figure 26.1 The clinical appearance of mild
CVI. Hemosiderin deposition is clearly visible.

Figure 26.2 Illustration of varicose veins that have developed into a case of CVI.

178 OSMOSIS.ORG

DEEP VEIN THROMBOSIS (DVT)
osms.it/deep-vein-thrombosis
PATHOLOGY & CAUSES
▪ Blood clotting in deep leg veins (iliofemoral,
popliteal, femoral veins)
▪ Arterial clots usually due to artery wall
damage; venous clots don’t require vein
damage
▪ Valves inside veins can lower blood
oxygen levels → venous stasis-associated
hypoxemia can activate reactive oxygen
species, other hypoxia-inducible factors →
tissue factor released into blood
▫ Tissue factor activation → prothrombin
turns into thrombin → fibrin fibers form
net → traps red blood cells, white blood
cells, platelets → venous thrombus
CAUSES
▪ Virchow’s triad
▪ Antiphospholipid syndrome
▪ Prolonged immobilization (bed rest,
orthopedic casts, long-distance air travel)
▪ Genetic
▫ Antithrombin, protein C, S deficiencies
RISK FACTORS
▪ Pregnancy, oral contraceptives, old age,
major surgery (e.g.orthopedic surgery),
malignancy, obesity, trauma, heart failure
COMPLICATIONS
▪ Pulmonary embolism (PE) most common
▫ Can cause pulmonary infarction, death
▪ Post-thrombotic syndrome
▫ Develops in 50% of individuals with
DVT
▪ Extreme cases: phlegmasia cerulea dolens
(blue, painful, swollen leg, possible venous
gangrene)
Chapter 26 Venous Dysfunction
SIGNS & SYMPTOMS
▪ 50% asymptomatic due to venous collateral
channels
▪ Localized inflammation around clot
▪ High venous pressure engorges visible
superficial veins
▪ If PE occurs: sudden dyspnea, chest pain
▫ Fatal if enough lung tissue affected
DIAGNOSIS
DIAGNOSTIC IMAGING
Doppler ultrasound imaging
▪ Most common diagnostic
▪ Modified vein diameter
▫ Increased: acute thrombus
▫ Decreased: chronic thrombus
▪ Absent colour flow: vein completely
occluded
▪ Increased flow in surrounding superficial
veins
Venography
▪ Most effective, but invasive/cost-prohibitive
LAB RESULTS
▪ D-dimers → rule out DVT
▫ Increased level: plasmin dissolves
thrombus
OTHER DIAGNOSTICS
Wells’ score
▪ Higher score indicates increased chance of
DVT (Scale of -2 to 9 points)
▫ High score = high chance: > 2 points
▫ Moderate score = moderate chance:
1–2 points
▫ Low score = low chance: < 1 point
OSMOSIS.ORG 179
 TREATMENT
MEDICATIONS
▪ Acute manifestation: unfractionated
heparin/low-molecular-weight heparins
▪ Long-term management: oral
anticoagulants (e.g. warfarin)
▪ Prior DVT: long term anticoagulation
therapy, antiplatelet treatment, parenteral
anticoagulants

OTHER INTERVENTIONS
▪ Preventative: calf exercises, compression
stockings/devices, raise affected areas to
decrease swelling

Figure 26.4 Clinical appearance of a deep

Figure 26.3 An IVC filter, used to prevent vein thrombosis of the right leg. The lower
embolization of the deep vein thrombus into leg is erythematous and swollen.
the pulmonary vasculature.

180 OSMOSIS.ORG
 NOTES

NOTES
PULMONARY VASCULAR
DISEASE

GENERALLY, WHAT IS IT?

PATHOLOGY & CAUSES DIAGNOSIS
▪ Diseases affecting blood flow through X-ray, chest CT scan, spirometry, ultra-
pulmonary vasculature, or fluid flow from sound, echocardiogram, ECG
vasculature
▪ Can be caused by process within lungs/
elsewhere in body TREATMENT
▪ Supportive, treat underlying disease,
SIGNS & SYMPTOMS optimize organ function (heart, lungs)

▪ Dyspnea, poor effort tolerance, chest pain,

tachypnea

Figure 129.1 Chronic thromboembolic pulmonary hypertension is an example of a pulmonary

vascular disease that originates outside the lungs. In this case, an embolism blocks the
pulmonary vessels, causing pulmonary blood pressure to rise beyond normal levels.

912 OSMOSIS.ORG

PULMONARY EDEMA
osms.it/pulmonary-edema
PATHOLOGY & CAUSES
▪ Alteration in Starling forces → build up of
fluid within interstitial space, air spaces of
lung
CAUSES
Cardiogenic (heart disease)
▪ Left sided heart failure → inefficient
pumping of blood from heart by left
ventricle → blood backs up into left atrium
→ pulmonary circulation → pulmonary
hypertension (raised hydrostatic pressure)
→ more fluid in lung interstitium →
pulmonary edema
▫ Severe systemic hypertension
(> 180/110mmHg) → left ventricle
cannot pump effectively against
extreme afterload → blood backs up into
left atrium → pulmonary circulation →
pulmonary edema
Non-cardiogenic (damage to pulmonary
capillaries or alveoli)
▪ Direct damage to alveoli/vasculature →
inflammatory response → leaky capillaries
▫ Pulmonary infection, toxin inhalation,
chest trauma, pulmonary vein occlusion,
burns
▫ Sepsis → systemic inflammation →
global edema
▫ Insufficient circulation of osmotically
active proteins, e.g. albumin → low
oncotic pressure in capillaries
▪ Malnutrition
▪ Liver failure
▪ Excessive protein loss (nephrotic syndrome,
protein losing enteropathies)
COMPLICATIONS
▪ Impaired gas exchange: oxygen/carbon
dioxide must diffuse through wide layer of
fluid → blood unable to fully saturate
Chapter 129 Pulmonary Vascular Disease
▪ Free fluid predisposes to secondary
infection
SIGNS & SYMPTOMS
▪ Dyspnea, productive cough (pink frothy
sputum), excessive sweating, anxiety,
tachycardia, end-inspiratory crackles,
dullness to percussion, cyanosis (decreased
hemoglobin saturation)
▪ Pulmonary edema in heart failure may also
include
▫ Orthopnea (shortness of breath worse
when lying flat)
▫ Paroxysmal nocturnal dyspnea
(episodes of severe sudden
breathlessness at night)
▫ Peripheral pitting edema
▫ Raised jugular venous pressure
▫ Hepatomegaly
DIAGNOSIS
DIAGNOSTIC IMAGING
Chest X-ray
▪ Kerley B lines (thickened subpleural
interlobular septa, usually seen at base of
lung)
▪ Increased vascular shadowing → batwing
perihilar pattern
▪ Upper lobe diversion (prominent upper lobe
pulmonary veins)
▪ Pleural effusion (if edema severe)
Non-contrast high resolution chest CT scan
▪ Airspace opacity
▪ Smooth thickening of interlobular septae
Chest ultrasound
▪ Detection of small amounts of fluid
▪ Echo-free space between visceral and
parietal pleura
▪ Septations in pleural fluid → underlying
OSMOSIS.ORG 913
 infection, chylothorax/hemothorax
Echocardiograph
▪ Evaluation of cardiac function, can
demonstrate left ventricular failure
LAB RESULTS
▪ Serum electrolytes
▪ Renal function
▪ Inflammatory markers
▪ Low oxygen saturation
▪ Increased carbon dioxide
Figure 129.2 A CT scan of the chest
in the coronal plane demonstrating the
peribronchovascular distribution of acute
pulmonary edema.
Figure 129.4 Illustration depicting pulmonary
edema.
914 OSMOSIS.ORG
TREATMENT
MEDICATIONS
▪ If cardiogenic
▫ Preload reduction: nitroglycerin,
diuretics, morphine sulphate
▫ Afterload reduction: ACE inhibitors,
angiotensin II receptor blockers,
nitroprusside
▪ If non-cardiogenic
▫ Manage illness (e.g. treat infection)
OTHER INTERVENTIONS
▪ Continuous positive airway pressure
(CPAP)
▪ Intubation: mechanical ventilation if level of
consciousness compromised
Figure 129.3 A plain chest radiograph
demonstrating pulmonary edema. There
is interstitial edema, represented by fine
stranded opacities known as Kerley B lines,
as well as alveolar edema, represented by
confluent nodular opacities.

Figure 129.5 The histological appearance of
pulmonary edema.
PULMONARY EMBOLISM
osms.it/pulmonary-embolism
PATHOLOGY & CAUSES
▪ Blockage of pulmonary artery by a
substance brought there via bloodstream
▪ Thrombus in remote site embolizes →
lodges in pulmonary vascular tree →
“pulmonary embolism”
▪ Obstruction of blood flow distal to
embolism → increased pulmonary vascular
resistance → increased pulmonary artery
pressure → increased right ventricular
pressure → cor pulmonale (if severe
obstruction)
▪ Regional decrease in lung perfusion →
dead space (ventilation, but no perfusion)
→ hypoxemia → tachypnea
Source of embolus
▪ Lower extremity deep vein thrombosis
▫ Most arise from deep veins above knee,
iliofemoral deep vein thrombosis
▫ Can arise from pelvic deep veins
▫ Pelvic thrombi tend to advance to more
proximal veins before embolizing
▪ Upper extremity deep veins (rarely)
▪ Uncommon embolic material: air, fat,
amniotic fluid
Chapter 129 Pulmonary Vascular Disease
RISK FACTORS
▪ Virchow’s triad: endothelial injury, stasis of
blood flow, blood hypercoagulability
▪ > 60 years old, malignancy, history of deep
vein thrombosis/pulmonary embolism,
hypercoagulable states, genetic disorders
(e.g. Factor V Leiden thrombophilia),
dehydration, prolonged immobilization
(bed rest, travel), cardiac disease, obesity,
nephrotic syndrome, major surgery, trauma,
pregnancy, estrogen-based medication (e.g.
oral contraceptives)
▪ Increased risk of fat embolism with bone
fractures (e.g. hip, femur)
SIGNS & SYMPTOMS
▪ Dyspnea, pleuritic chest pain, cough,
hemoptysis
▪ Signs, symptoms of deep vein thrombosis
▫ Tender, swollen, erythematous
extremity
▪ Syncope
▪ Often asymptomatic (in the case of small
emboli)
OSMOSIS.ORG 915
 MNEMONIC: TOM ▪ Low SpO2, tachypnea, rales, tachycardia,
SCHREPFER S4 heart sound, increased P2 (closure of
Risk factors for Pulmonary pulmonary valve), shock, low-grade fever,
embolism decreased breath sounds, percussion
Trauma dullness, pleural friction rub, sudden death
(pulmonary saddle embolism)
Obesity
Malignancy
Surgery DIAGNOSIS
Cardiac disease
Hospitalization Wells’ score
Rest (bed-ridden) ▪ Used to assess probability of pulmonary
Elderly embolism (multiple different probability
Past history tests available)
Fracture ▫ Score > 4: pulmonary embolism likely,
consider diagnostic imaging
Estrogen (pregnancy, post-
partum) ▫ Score ≤ 4: pulmonary embolism unlikely,
consider D-dimer test to rule out
Road trip

Figure 129.6 A CT pulmonary angiogram

demonstrating a pulmonary embolus and
subsequent right middle lobe infarct.

916 OSMOSIS.ORG

DIAGNOSTIC IMAGING
Chest X-ray
▪ Typically normal
CT pulmonary angiography
▪ Definitive test
▪ Visualize decreased blood supply
Venous duplex ultrasound
▪ Of lower extremities
▫ May reveal origin of pulmonary
embolism
▫ Negative result does not exclude
pulmonary embolism
Ventilation-perfusion scan
▪ Normal scan rules out pulmonary embolism
LAB RESULTS
▪ D-dimer (high negative predictive value)
▫ Positive result does not prove
pulmonary embolism
▫ Negative result rules out pulmonary
embolism
▪ Arterial blood gas
▫ ↓ PaO2 → hypoxemia
▫ Hyperventilation → ↑ PaCO2 → ↑ pH →
respiratory alkalosis
▫ A-a gradient elevated (indicated V/Q
mismatch)
▪ Tests for causes of secondary pulmonary
embolism
▫ Full blood count, clotting profile,
erythrocyte sedimentation rate, renal
function, liver function, electrolytes
OTHER DIAGNOSTICS
ECG
▪ Excludes other causes of chest pain
▪ ECG features of pulmonary embolism (or
any pulmonary hypertension) include
▫ Sinus tachycardia
▫ Right bundle branch block
▫ Right ventricular strain pattern: T wave
inversion in right precordial (V1–V4), and
inferior leads (II, III, aVF)
▫ Right atrial enlargement (P pulmonale)
▫ Right atrial dilatation → right axis
deviation
Chapter 129 Pulmonary Vascular Disease
▫ Dominant R wave in V1
▫ S1Q3T3 pattern: Deep S wave in lead I,
Q wave in lead III, negative wave in lead
III
▪ Nonspecific ST segment, T wave changes
▪ Pulmonary embolism can be excluded if
▫ SaO2 exceeds 95%
▫ Age < 50
▫ No unilateral leg swelling, hemoptysis,
history of deep vein thrombosis/
pulmonary embolism, recent surgery/
trauma, hormone use (or estrogen-
based medications), tachycardia
TREATMENT
MEDICATIONS
Anticoagulation
▪ Acute phase (days–weeks)
▫ Prevent further thromboembolic events
▫ Unfractionated heparin, low molecular
weight heparin, fondaparinux
▪ Long-term (vitamin K antagonists)
▫ Warfarin, acenocoumarol,
phenprocoumon
Thrombolysis
▪ Used for massive pulmonary embolism
causing hemodynamic instability
▪ Carries risk of secondary hemorrhage
▪ Thrombolytics used to break up clots
▫ Streptokinase, staphylokinase,
urokinase, anistreplase
▫ Recombinant tissue plasminogen
activators (alteplase, reteplase,
tenecteplase)
SURGERY
Pulmonary thromboendarterectomy
▪ Surgical removal of a chronic
thromboembolism
▪ Rare
Inferior vena cava filter
▪ Vascular filter inserted into inferior vena
cava to prevent life-threatening pulmonary
emboli
▪ Indications: anticoagulant therapy
contraindicated, major embolic event
OSMOSIS.ORG 917
 despite anticoagulation

OTHER INTERVENTIONS
Preventative measures
▪ Unfractionated heparin, low molecular
weight heparin
▪ Factor Xa inhibitor
▪ Long-term low-dose aspirin
▪ Anti-thrombosis compression stockings/
intermittent pneumatic compression

Figure 129.7 A plant chest radiograph of

the same individual, demonstrating the
pulmonary infarct which is visible as a wedge
shaped opacity in the lateral art of the right
lung field.

Figure 129.8 The gross pathological

appearance of a pulmonary embolus.

Figure 129.9 The ECG changes associated with a pulmonary embolism. There is a right bundle
branch block, sinus tachycardia and T-wave inversions in leads V1-3 and III.

918 OSMOSIS.ORG

PULMONARY HYPERTENSION
osms.it/pulmonary-hypertension
PATHOLOGY & CAUSES
▪ Increased blood pressure in pulmonary
circulation
▪ Mean pulmonary arterial pressure >
25mmHg (normal ~15mmHg)
▪ Pulmonary hypertension → excess fluid in
pulmonary interstitium (pulmonary edema)
→ impaired gas exchange
▪ Pulmonary hypertension → strain on right
heart → hypertrophy → right heart oxygen
demand eventually exceeds supply →
right-sided heart failure
▫ Right heart failure caused by lung
disease → cor pulmonale → backup
of blood in venous system → signs,
symptoms of right heart failure
▪ Raised jugular venous pressure
▪ Fluid build up in liver → hepatomegaly
▪ Fluid build up in legs → leg edema
▪ Left ventricle receives less blood →
compensation → pumps harder, faster
(tachycardia)
TYPES
Group I
▪ Pulmonary arterial hypertension,
pulmonary veno-occlusive disease,
pulmonary capillary hemangiomatosis
▪ Abnormal increase in pulmonary arteriolar
resistance → increased strain on right heart
(pumping fluid through narrower pipe)
▪ Damage to endothelial cells lining
pulmonary arteries → release of
endothelin-1 serotonin, thromboxane,
produce less nitric oxide and prostacyclin
→ constriction of arterioles, hypertrophy of
smooth muscle → pulmonary hypertension
▪ Over time affected vessels become stiffer,
thicker (fibrosed) due to vasoconstriction,
thrombosis, vascular remodeling → greater
increase in blood pressure in lungs, more
strain on right heart
Chapter 129 Pulmonary Vascular Disease
▪ Idiopathic, inherited, drug/toxin associated
causes connective tissue disease, HIV
infection, portal hypertension congenital
heart disease (shunting)
Group II
▪ Pulmonary hypertension secondary to left
heart disease
▪ Pulmonary hypertension due to left heart
disease (heart failure, valvular dysfunction)
→ left heart fails to pump blood efficiently
→ backup of blood in pulmonary veins,
capillary beds → increased pressure in
pulmonary artery → pulmonary edema,
pleural effusion
▪ Raised back pressure may trigger
secondary vasoconstriction → increased
right heart strain
▪ Common causes include
▫ Left ventricular systolic/diastolic
dysfunction
▫ Valvular heart disease
▫ Congenital/acquired in/out-flow tract
obstruction
▫ Congenital cardiomyopathy
▫ Pulmonary venous stenosis
Group III
▪ Pulmonary hypertension due to lung
disease/chronic hypoxia
▪ Low oxygen levels in alveoli pulmonary
arteries constrict
▪ Chronic lung disease → region of diseased
lung → inefficient/total lack of gas
exchange → hypoxic vasoconstriction
(pulmonary arterioles) → shunting of blood
away from damaged areas
▪ Prolonged alveolar hypoxia across wide
portion of pulmonary vascular bed →
increase in pulmonary arterial pressure →
thickening of pulmonary vessel walls →
greater effort required from right heart →
sustained pulmonary hypertension
▪ Causes include
▫ COPD
OSMOSIS.ORG 919
 ▫ Interstitial lung disease
▫ Mixed restrictive/obstructive pattern
disease
▫ Sleep-disordered breathing
▫ Alveolar hypoventilation
▫ Chronic exposure to high altitude
Group IV
▪ Chronic arterial obstruction/
thromboembolic disease
▪ Recurrent blood clots in pulmonary
vasculature
▪ Blockage/narrowing of pulmonary vessel
with unresolved obstruction (e.g. clot)
→ increased pressure, shear stress
(turbulence) in pulmonary circulation
→ vessel wall remodelling → sustained
pulmonary hypertension
▪ Causes endothelium to release histamine,
serotonin → constriction of pulmonary
arterioles → rise in pulmonary blood
pressure → chronic thromboembolic
pulmonary hypertension
▪ Other causes of arterial obstruction
▫ Angiosarcoma, arteritis, congenital
pulmonary artery stenosis, parasitic
infection
Group V
▪ Unclear/multifactor mechanisms
▪ Hematologic disease (e.g. hemolytic
anemia)
▪ Systemic disease (e.g. sarcoidosis,
vasculitis)
▪ Metabolic disorders (e.g. glycogen storage
disease, thyroid disease)
▪ Other (e.g. microangiopathy, chronic kidney
disease)
RISK FACTORS
▪ Family history, prior pulmonary embolic
events, HIV/AIDS, sickle cells disease,
cocaine use, COPD, sleep apnea, living at
high altitude, mitral valve pathology
920 OSMOSIS.ORG
SIGNS & SYMPTOMS
▪ Dyspnea, syncope, fatigue, chest pain,
poor effort tolerance, loss of appetite,
lightheadedness, orthopnea (left-sided
heart failure)
▪ Tachycardia, cyanosis, parasternal heave
▪ Signs of systemic congestion/right heart
failure:
▫ Loud pulmonic component of second
heart sound (P2)
▫ Jugular venous distension
▫ Ascites
▫ Hepatojugular reflux
▫ Lower limb edema
DIAGNOSIS
DIAGNOSTIC IMAGING
Chest X-ray
▪ Enlarged pulmonary arteries
▪ Lung fields may or may not be clear,
dependent on underlying cause
Echocardiogram
▪ Increased pressure in pulmonary arteries,
right ventricles → dilated pulmonary artery
▪ Dilatation/hypertrophy of right atrium, right
ventricle
▪ Large right ventricle → bulging septum
Ventilation/perfusion scan
▪ Identity / exclude ventilation-perfusion
mismatches
OTHER DIAGNOSTICS
Right heart catheterisation (gold standard)
▪ Catheter into right heart → most accurate
measure of pressures
ECG
▪ Right heart strain pattern: T wave inversion
in right precordial (V1–V4), and inferior leads
(II, III, aVF)
Spirometry
▪ Unidentified underlying cause
 Chapter 129 Pulmonary Vascular Disease

with prostanoids, phosphodiesterase

TREATMENT inhibitors, endothelin antagonists
▪ Pulmonary arterial hypertension
MEDICATIONS
▫ Endothelin receptor antagonists
▪ Pulmonary hypertension secondary to
left ventricular failure → optimize left ▫ Prostanoids
ventricular function
▫ Diuretics (cautiously—individuals may SURGERY
be preload dependent) ▪ Lung transplant
▫ Digoxin ▪ Repair/replace damaged valves to optimize
▫ Anticoagulants left ventricular function
▪ Cardiogenic pulmonary arterial
hypertension
▫ Relax smooth muscle (promote
vasodilation), reduce vascular
remodelling, improve exercise capacity

Figure 129.10 The gross pathological appearance of the pulmonary arteries in a case of
pulmonary hypertension. The underlying pathological process is similar to atherosclerosis found
elsewhere in the cardiovascular system.

OSMOSIS.ORG 921
 Figure 129.12 The histological appearance
of a pulmonary artery in a case of pulmonary
hypertension. There is marked thickening of
both the intima and the media.
Figure 129.11 A CT scan of the chest in the
axial plane demonstrating enlargement of
the pulmonary trunk as a consequence of
pulmonary hypertension.

922 OSMOSIS.ORG

NOTES
ACUTE RESPIRATORY DISEASE
GENERALLY, WHAT IS IT?
PATHOLOGY & CAUSES
▪ Acute respiratory disorders induced by
changes in atmospheric pressure/direct
communication between atmosphere,
vasculature/pulmonary conditions, diseases
(e.g. pulmonary trauma, pneumonia, sepsis,
severe burns)
▪ Impaired alveolar gas exchange →
hypoxemia
▪ Can lead to potentially fatal conditions
SIGNS & SYMPTOMS
▪ Hypoxemia: dyspnea, tachypnea, chest
pain
ACUTE RESPIRATORY DISTRESS
SYNDROME (ARDS)
osms.it/ards
PATHOLOGY & CAUSES
▪ Acute lung condition
▪ Widespread diffuse inflammation →
increased vascular permeability, loss of
pulmonary tissue
▪ Triggered by pulmonary conditions,
diseases (e.g. pulmonary trauma,
pneumonia, sepsis)
PATHOLOGY
▪ Refractory hypoxemia, reduced pulmonary
compliance, pulmonary edema without
NOTES
DIAGNOSIS
DIAGNOSTIC IMAGING
▪ Medical imaging
OTHER DIAGNOSTICS
▪ Clinical presentation, history
▪ Arterial blood gases
TREATMENT
OTHER INTERVENTIONS
▪ Oxygen therapy
▪ Mechanical ventilation
cardiovascular cause (noncardiogenic
pulmonary edema)
▪ Alveolar barrier cells damaged → alveolar
sacs flooded → impairs air exchange
▫ Pro-inflammatory cytokines released:
tumor necrosis factor (TNF), interleukins
▫ Interleukins (IL-1, IL-6, IL-8) →
neutrophil activation → toxic substances
(reactive oxygen species) released →
alveolar and capillary damage → oncotic
gradient lost → no fluid resorption →
fluid in interstitium
▪ Damaged Type II pneumocytes →
surfactant layer malfunction
OSMOSIS.ORG 867
 ▪ Acute inflammatory response → abnormal
extravascular fibrin deposition
▫ Increased activity of extrinsic
coagulation pathway
▫ Impaired fibrinolysis

CAUSES
▪ Systemic infections/septic shock
▪ Acute lung injury
▫ Compromises ability to regulate gas
exchange → lungs fill up with fluid in
interstitium, alveoli
▪ Gastric contents aspiration
▪ Severe pneumonia
▪ Serious burns
▪ Mechanical (e.g. near drowning) Figure 123.1 A chest radiograph
▪ Inflammatory (e.g. pancreatitis) demonstrating diffuse, bilateral, coalescent
opacities resembling ground glass.

SIGNS & SYMPTOMS

OTHER DIAGNOSTICS
▪ Usually begin within first few hours, 1–2
days 2012 Berlin definition
▪ Dyspnea, tachypnea, tachycardia, ▪ Acute pulmonary injury within week of
diaphoresis, low blood oxygenation clinical consultation
→ cyanosis, diffuse crackles on lung ▪ Bilateral opacities on chest X-ray/CT
auscultation scan unexplained by other pulmonary
pathologies (e.g. pleural effusion, lung
collapse)
DIAGNOSIS ▪ Respiratory failure without heart failure
(noncardiogenic)
DIAGNOSTIC IMAGING ▪ Minimum positive end expiratory pressure
Chest X-rays (PEEP) of 5cmH20
▪ Bilateral alveolar infiltrate, pulmonary ▪ Reduced oxygen in arteries, reduced partial
edema with no cardiovascular cause pressure arterial oxygen/fraction of intake
of oxygen (PaO2/FiO2) ratio
CT scan ▫ Mild: 201–300mmHg
▪ Bilateral airspace opacities ▫ Moderate: 101–200mmHg
▫ Serious: < 100mmHg
Ultrasound
▪ Subpleural consolidations, pleural line
irregularities, no lung gliding TREATMENT
LAB RESULTS MEDICATIONS
▪ Respiratory alkalosis → respiratory acidosis ▪ Antibiotic therapy
▫ After microbiological culture, determines
appropriate course of antibiotics
▪ Diuretics
▫ Manage fluid output

868 OSMOSIS.ORG
 Chapter 123 Acute Respiratory Disease

OTHER INTERVENTIONS
Mechanical ventilation
▪ Maintain gas exchange to meet metabolic
demands
▪ Endotracheal intubation/tracheostomy
(prolonged intubations)
▪ Monitor parameters
▫ PEEP: keep alveoli from collapsing,
improve oxygenation
▫ Mean airway pressure: recruit alveoli to
open
Figure 123.2 The histological appearance ▫ Plateau pressure: monitor alveoli for
of diffuse alveolar damage, the pathological overdistension
correlate of ARDS. There is a diffuse ▪ Extracorporeal membrane oxygenation
inflammatory cell infiltrate and pink, hyaline (ECMO)
membranes in the alveolar spaces.
▫ Removes blood from body, artificially
removes CO2, oxygenates red blood
cells

Figure 123.3 The gross pathological

appearance of ARDS. There is a diffuse,
vaguely nodular infiltrate, most easily visible
at the apices.

OSMOSIS.ORG 869
 ALTITUDE SICKNESS
osms.it/altitude-sickness
cell production
PATHOLOGY & CAUSES ▪ ↑ 2,3 BPG synthesis → ↓ hemoglobin
affinity for O2 → ↑ release of oxygen to
▪ Reaction to exposure to low oxygen tissues
concentrations when traveling to high
altitude Measures to avoid HAI
▫ AKA high altitude illness (HAI), acute ▪ Acclimatization: ascending slowly to high
mountain sickness (AMS) altitudes, to adjust to decreasing oxygen
▪ Partial pressure of oxygen of inspired air levels
calculated by PiO2 (mmHg) = FiO2 (%) x ▪ Preventative medications: acetazolamide
[Pb (mmHg) - 47mmHg] (diuretic); increases bicarbonate kidney
▫ FiO2: fraction of inspired oxygen, not excretion
affected by altitude, remains unchanged
in 21%
RISK FACTORS
▫ Pb: barometric pressure
▪ History of HAI episodes
▫ 47mmHg: vapor pressure of water at
▪ Prior exercise/alcohol consumption
37°C/98.6°F
▪ Rapid ascent to high altitude
▪ In high altitudes, ↓ Pb → ↓ PiO2
▪ Comorbidities that affect breathing (e.g.
▪ Partial pressure of alveolar oxygen (PAO2)
asthma)
▫ Pressure in alveolar space after
equilibration with blood
▪ PAO2 lower than PiO2 COMPLICATIONS
▫ Air enters lungs, humidified by upper ▪ Can lead to potentially fatal conditions
airway, partial pressure of water vapor ▫ High altitude cerebral edema (HACE),
reduces partial pressure of oxygen high altitude pulmonary edema (HAPE)
▫ Continual uptake of oxygen from alveoli
by pulmonary capillaries
SIGNS & SYMPTOMS
▫ Continual diffusion of CO2 from
capillaries into alveoli
▪ Usually appear within 6–12 hours of ascent
▪ ↓ PiO2 → ↓ PAO2, ↓ PaO2 → hypoxemia
▪ Headache, dizziness, fatigue, nausea,
▪ HAI starts at 1.5km/5,000ft, symptoms vomiting, loss of appetite, sleep disturbance
noticeable above 2.4km/8,000ft
▪ Often improves with time if person does
Adaptive mechanisms not ascend to higher altitude
▪ Hypoxemia → hyperventilation → ↑ ▪ HACE
expiration of CO2 by lungs → ↓ PCO2 → ↑ ▫ Excessive fatigue, confusion, neurologic
pH (respiratory alkalosis) deficits (e.g. ataxia, altered mental state)
▪ ↓ PCO2 , ↑ pH inhibit central, peripheral ▪ HAPE
chemoreceptors, decrease ventilation rate ▫ Dry cough, dyspnea
▪ Within several days ↑ HCO3-, ↓ H+
kidney excretion → ↓ pH → stimulation
of respiratory center to further increase
ventilation
▪ ↑ erythropoietin production → ↑ red blood

870 OSMOSIS.ORG
 Chapter 123 Acute Respiratory Disease

DIAGNOSIS
LAB RESULTS
▪ Arterial blood gases
▫ ↓ PaO2, ↑ PaCO2, respiratory alkalosis

OTHER DIAGNOSTICS
▪ Clinical presentation, history of living at low
altitude, recent ascent at high altitude

TREATMENT
MEDICATIONS
▪ Symptom relief
▫ E.g. analgesics for headache,
Figure 123.4 A chest radiograph
antiemetics for nausea
demonstrating acute pulmonary edema in an
▪ Carbonic anhydrase inhibitors (e.g. individual who ascended to 2700m.
acetazolamide)
▫ Increase HCO3- excretion; treat
respiratory alkalosis

OTHER INTERVENIONS
▪ Rest
▪ Descent
▪ Symptom relief
▫ E.g. oxygen to improve breathing
▪ HACE, HAPE
▫ Medical emergencies; require immediate
descent/oxygen administration

DECOMPRESSION SICKNESS (DCS)

osms.it/decompression_sickness
PATHOLOGY & CAUSES
▪ Gas embolism, occurs when individuals
experience sudden decreases in
atmospheric pressure
▫ AKA diver’s disease
▪ Air breathed at relatively high pressure
(e.g. diver descends from water surface)
→ inspired gases compressed to higher
pressure of surrounding water → ↑ partial
pressure of oxygen, nitrogen → ↑ oxygen,
nitrogen dissolved in blood, loaded in body
tissues
▫ Henry’s law: at constant temperature,
amount of gas dissolved in liquid
directly proportional to partial pressure
▪ If oxygen, nitrogen quantities high enough
→ oxygen toxicity/nitrogen narcosis,
respectively

OSMOSIS.ORG 871
 ▪ Pressure drops too rapidly (e.g. ascent
to water surface) → sum of gas tensions
in tissue exceeds ambient pressure →
liberation of free gas from tissues due to
excess dissolved gases → gas bubbles
→ vessels blocked, tissues compressed,
clotting cascade, inflammation
▪ Occurs in scuba, deep sea divers,
underwater construction workers; during
rapid ascent of an unpressurized aircraft
▪ Caisson disease (chronic decompression
sickness)
▫ Tunnel workers, moving from caisson to
atmospheric pressure
RISK FACTORS
▪ Right-to-left shunt (e.g. patent foramen
ovale/atrial/ventricular septal defect)
▪ Air travel after diving
▪ More common in individuals who are
biologically male
DIAGNOSIS
OTHER DIAGNOSTICS
▪ Clinical presentation, history of exposure to
sudden decreases in atmospheric pressure
▪ Confirmed if symptoms relieved after
recompression
TREATMENT
OTHER INTERVENTIONS
▪ Hyperbaric oxygen therapy in
recompression chamber
▫ Under high pressure gas bubbles forced
back into solution; slow decompression
permits gradual gas elimination via
lungs, prevents obstructive bubbles
reforming

SIGNS & SYMPTOMS

▪ Usually develop within one hour of
surfacing
▪ Excessive fatigue, headache
▪ Depend upon size, location of gas bubbles

Type I DCS
▪ Skeletal muscles, joints
▫ Painful condition, AKA “the bends”;
arching of back, posture reminiscent of
Grecian bend
▪ Skin
▫ Itching, rash

Type II DCS (more severe)

▪ Nervous system
▫ Paresthesia, amnesia, weakness,
paralysis
▪ Lungs
▫ Edema, hemorrhage, atelectasis,
emphysema → respiratory distress,
AKA “the chokes”; cough, chest pain,
dyspnea
▪ Can progress to permanent injuries/fatal
damage

872 OSMOSIS.ORG
Chapter 123 Acute Respiratory Disease

OSMOSIS.ORG 873
 NOTES

NOTES
OBSTRUCTIVE LUNG DISEASE

GENERALLY, WHAT IS IT?

OTHER DIAGNOSTICS
PATHOLOGY & CAUSES
Spirometry/pulmonary function test (PFTs)
▪ Obstruction of airflow from lungs ▪ Tidal volume (TV)
▪ Increased resistance to airflow → air- ▫ Volume of air inspired, expired during
trapping quiet breathing
▪ Classifications ▪ Residual volume (RV)
▫ Narrowing of lumen wall (e.g. asthma, ▫ Volume of air left in lung after maximal
chronic bronchitis) expiration
▫ Increasing pressure external to ▪ Forced vital capacity (FVC)
airway/loss of lung parenchyma (e.g. ▫ Maximum volume of air that can be
emphysema) expired after maximal inspiratory effort
▫ Obstruction of airway lumen (e.g. ▪ Forced expiratory volume (FEV)
bronchiectasis, chronic bronchitis) ▫ Volume of air forcibly exhaled per unit
of time
COMPLICATIONS ▪ Peak expiratory flow rate (PEFR)
▪ Cor pulmonale, right ventricular ▫ During FEV, maximum flow of expiration
hypertrophy ▪ Functional residual capacity (FRC)
▫ Volume of air left in lungs after quiet
expiration
SIGNS & SYMPTOMS
▪ Cough, thick mucus, dyspnea, wheezing TREATMENT
▪ See individual diseases
DIAGNOSIS
DIAGNOSTIC IMAGING
Chest X-ray/CT scan

LAB RESULTS
▪ Sputum culture
▪ Arterial blood gas (ABGs)

886 OSMOSIS.ORG
 Chapter 126 Obstructive Lung Disease

ALPHA 1-ANTITRYPSIN (A1AT)

DEFICIENCY
osms.it/a1at-deficiency
amounts A1AT proteins
PATHOLOGY & CAUSES ▫ Heterozygous individuals have 60%
normal levels (enough to protect lungs
▪ Autosomal dominant (codominant) genetic in non-smokers)
disorder
▫ Increased risk of lung/liver disease
▫ Decreased production/absence of A1AT
▪ PiZZ
→ overaction of proteases → damaged
alveoli → damaged lungs, liver ▫ Homozygous
▪ Lungs ▫ Individuals only have 15–20% normal
levels
▫ Damaged alveoli inflammation →
neutrophils secrete elastase → absence ▫ Much higher risk of lung/liver disease
of/decreased A1AT → elastase overacts, ▫ Can live without lung/liver disease if
inflames → increased breakdown of environmental exposures minimal
elastin → alveoli lose elasticity, integrity ▫ Infants can develop liver failure during
→ chronic obstructive pulmonary first years of life
disease (COPD) ▫ Individuals with no production of A1AT
▪ Liver = no liver disease
▫ Genetic mutation → misfolded A1AT
build up in endoplasmic reticulum of COMPLICATIONS
hepatocytes → kill hepatocytes →
▪ COPD (emphysema, bronchiectasis, chronic
cirrhosis
bronchitis), hepatocellular carcinoma, liver
cirrhosis, chronic hepatitis
CAUSES
▪ Smoking
▫ Earlier onset of COPD in individuals with SIGNS & SYMPTOMS
A1AT deficiency
▪ Genetics ▪ COPD: shortness of breath, wheezing,
mucus production, chronic cough
▫ Serine protease inhibitor, clade A,
member 1 (SERPINA1) encodes ▪ Liver damage, cirrhosis, impaired liver
A1AT protein, located on long arm of function: inability to make coagulation
chromosome 14 factors, hepatic encephalopathy, portal
hypertension, esophageal varices, jaundice,
▪ Pi*M
hepatocellular carcinoma
▫ Normal allele
▪ Pi*Z (most common)
▫ Mutated/diseased allele
▫ Misfolded A1AT proteins aggregate
→ stick in endoplasmic reticulum of
hepatocytes → kill hepatocytes
▪ PiMZ
▫ Heterozygous (one normal allele, one
diseased allele)
▫ Mutated gene contributes 10% normal

OSMOSIS.ORG 887
 DIAGNOSIS TREATMENT
DIAGNOSTIC IMAGING MEDICATIONS
▪ Augmentation therapy
Liver ultrasound
▫ Intravenous (IV) infusions of A1AT
Chest X-ray/CT scan protein from plasma donors
▪ Hyperinflated/damaged lungs, basilar ▫ Not curative, only slows progression
emphysema, panlobular emphysema ▪ Inhalers, supplemental oxygen
▫ Smoking: apically distributed ▫ COPD
emphysema ▪ Lactulose
▫ Prevent hepatic encephalopathy
LAB RESULTS ▫ For liver cirrhosis
▪ Serum A1AT levels
▪ Family history, genetic testing SURGERY
▪ Liver biopsy ▪ Liver transplant
▫ Esp. homozygous infants, liver failure
OTHER DIAGNOSTICS during first years
▪ PFT ▪ Lung transplant
▫ Measure rate air exits lungs
▪ Periodic acid-Schiff (PAS)
▫ Diastase-resistant pink globules in liver
biopsy
▫ Stains A1AT pink

Figure 126.2 A CT scan of the chest in

the axial plane demonstrating panlobular
emphysema as a consequence of alpha
1-antitrypsin deficiency.

Figure 126.1 The histological appearance

of the liver in an individual with alpha
1-antitrypsin deficiency. There are globular
inclusions within periportal hepatocytes.

888 OSMOSIS.ORG

ASTHMA
osms.it/asthma
PATHOLOGY & CAUSES
▪ Hyperresponsiveness disorder, reversible
airflow obstruction
▪ Chronic inflammation, narrowing of airways
▪ Acute (Type 1 hypersensitivity reaction)
▫ Initial sensitization to allergen →
production of cluster of differentiation 4
(CD4), T helper 2 (Th2) cells → release
interleukin 4 (IL4), interleukin 5 (IL5) →
environmental trigger → eosinophils,
mast cells release inflammatory
mediators in bronchial walls (e.g.
histamine, leukotrienes) → degradation
of lipids, proteins, nucleic acids → tissue
destruction → strong inflammatory
reaction in bronchiolar walls → smooth
muscle of bronchioles spasm, mucus in
narrow airways increases → difficulty
breathing
▫ Vasodilation of pulmonary vasculature,
increased capillary permeability →
edema
▫ Increased mucus production by goblet
cells → impaired mucociliary function
▪ Chronic inflammation → scarring, fibrosis
→ thickening of epithelial basement
membrane → permanently narrows airway
▪ Th2 cells release IL5 → attract, activate
eosinophils
▪ Neutrophils release cytokines
▫ Interleukin 8 (IL8)
▫ More severe for individuals with
neutrophilic asthma
▪ Triggers
▫ Air pollution, cigarette smoke, dust,
pet dander, cockroaches, mold, pollen,
medications (e.g. aspirin, beta-blockers)
TYPES
Extrinsic
▪ Type 1 hypersensitivity reaction triggered
by extrinsic allergens (e.g. dust, mold)
Chapter 126 Obstructive Lung Disease
▪ Individuals with atopic family history to
allergies
▪ Atopic triad
▫ Asthma, atopic dermatitis, allergic
rhinitis
Intrinsic
▪ Nonimmune
▪ Viral infections, stress, exercise, smoking
SIGNS & SYMPTOMS
▪ Coughing, chest tightness, dyspnea,
difficulty breathing, wheezing, whistling
during expiration
▪ Curschmann spirals in sputum
▫ Spiral-shaped mucus plugs
▫ Casts from small bronchi
▫ Blocks air exchange, inhaled
medications from reaching inflammation
▪ Charcot–Leyden crystals in sputum
▫ Needle-shaped, formed from
breakdown of eosinophils
DIAGNOSIS
OTHER DIAGNOSTICS
▪ Trigger test, spirometry, peak air flow
▪ Classifications based on frequency of
symptoms (esp. night/morning), forced
expiratory volume in one second (FEV1),
PEFR, frequency of medication use
(intermittent, mild persistent, moderate
persistent, severe persistent)
TREATMENT
OTHER INTERVENTIONS
▪ No cure; treatments manage symptoms,
prevent asthma attack
▪ Avoid triggers
OSMOSIS.ORG 889
890 OSMOSIS.ORG

Figure 126.3 A chest radiograph
demonstrating hyperinflation in an
individual with chronic asthma. There is a
pneumothorax in the right lower zone.
BRONCHIECTASIS
osms.it/bronchiectasis
PATHOLOGY & CAUSES
▪ Chronic inflammation → permanent dilation
of bronchi, bronchioles → destruction of
airways
▫ Damage to mucociliary “elevator” →
mucus, bacteria accumulates
CAUSES
Chronic inflammation
▪ Primary ciliary dyskinesia
▫ Absence of dynein arm in cilia → cilia
move abnormally → mucus stuck in
airways → bacteria in mucus multiply →
pneumonia → chronic inflammation
▪ Cystic fibrosis (most common)
▫ Mucus too sticky → hard for cilia to
sweep → mucus accumulates →
recurrent pneumonias → chronic
inflammation, infection
Chapter 126 Obstructive Lung Disease
Airway obstruction
▪ E.g. tumor inside/outside airway, lodged
foreign object
▪ Blockage prevents mucociliary escalator
from clearing mucus → recurrent
pneumonias → chronic inflammation
Infections
▪ E.g. aspergillosis, tuberculosis, adenovirus,
Haemophilus influenzae, Staphylococcus
aureus; hypersensitivity response →
inflammation
▫ Chronic inflammation → immune cells,
cytokines damage cilia, elastin fibers →
airways dilated, clogged with mucus
→ fibroblasts deposit collagen → loss
of elastin, buildup of collagen → lungs
less elastic → more difficult for air to
move smoothly → lung function declines
→ hypoxia → pulmonary arterioles
constrict to divert blood away from
damaged areas of lung → increased
OSMOSIS.ORG 891
 pulmonary vascular resistance →
right ventricular hypertrophy → cor
pulmonale → inflammation of pleura

SIGNS & SYMPTOMS

▪ Wheezing, productive cough, foul smelling
mucus, dyspnea, hemoptysis, recurrent/
persistent pneumonia, basilar crackles
▪ Long term hypoxia
▫ Digital clubbing

DIAGNOSIS
DIAGNOSTIC IMAGING
CT scan
▪ Dilated bronchi/bronchioles

Chest X-ray
▪ Increased bronchial markings at lung
periphery

LAB RESULTS
Figure 126.4 The gross pathological
▪ Sputum culture
appearance of the lungs in a case of severe
▪ Genetic testing bronchiectasis.

OTHER DIAGNOSTICS
▪ Spirometry
▫ FEV1 decreased, FEV1/FVC ratio
decreased
▪ Sweat test

TREATMENT
MEDICATIONS
▪ Bronchodilators; beta-2 agonists (e.g.
albuterol)
▪ Inhaled corticosteroids (e.g. fluticasone
Figure 126.5 The histological appearance
▪ Antibiotics of bronchiectasis complicated by fungal
▫ Recurrent pneumonias colonisation. There is a heavily dilated
bronchus containing an aggregation of
OTHER INTERVENTIONS fungus known as an aspergilloma.
▪ Percussion, postural drainage
▫ Recurrent pneumonias
▪ Pulmonary hygiene
▪ Adequate hydration

892 OSMOSIS.ORG
 Chapter 126 Obstructive Lung Disease

CHRONIC BRONCHITIS
osms.it/chronic-bronchitis

PATHOLOGY & CAUSES DIAGNOSIS

▪ Preventable, progressive pulmonary DIAGNOSTIC IMAGING
disease
Chest X-ray
▫ Chronic airway inflammation, limited
airflow ▪ Large, horizontal heart, increased bronchial
markings
▫ Bronchial tubes in lungs inflame →
productive cough
▪ Subset of COPD LAB RESULTS
▪ Exposure to irritants → hypertrophy/ ▪ ABGs
hyperplasia of bronchial mucous glands, ▫ Respiratory acidosis (arterial PCO2
goblet cells in bronchioles, cilia less mobile > 45mmHg, bicarbonate > 30mEq/L)
→ increased mucus production, less
movement → mucus plugs → obstruction
in bronchioles → air-trapping → productive
OTHER DIAGNOSTICS
cough ▪ Productive, mucinous cough
▪ Blocked airflow, air-trapping → increased ▫ At least three months over two
partial pressure of CO2 in lungs → less consecutive years
O2 reaches blood → cyanosis (if severe); ▪ PFTs
individuals referred to as “blue bloaters” ▫ Increased TLC, air-trapping; decreased
FVC1/FVC ratio
RISK FACTORS ▪ Postmortem measurement
▪ Smoking (primary cause), cystic fibrosis, ▫ Reid index (measure ratio of thickness
sulfur, nitrogen dioxide, dust, silica, family of bronchial mucinous glands, total
history, genetic predisposition thickness of airway, epithelium to
cartilage)
▫ > 40% (due to hyperplasia, hypertrophy
COMPLICATIONS of glands)
▪ Pulmonary hypertension, increased
workload of right ventricle, cor pulmonale,
infections distal to mucus blockages, TREATMENT
fibrosis of terminal bronchioles,
compensatory polycythemia MEDICATIONS
▪ Supplemental oxygen, bronchodilators,
inhaled steroids, antibiotics
SIGNS & SYMPTOMS
▫ Manage symptoms
▪ Wheezing (due to mucus, narrow airway), ▪ Prophylactic vaccination against
crackles/rales (small airways pop open influenza, Streptococcus pneumoniae (S.
during air movement due to narrow pneumoniae)
passageway)
▪ Hypoxemia, hypercapnia (due to mucus OTHER INTERVENTIONS
plugs blocking air flow) → cyanosis → ▪ Smoking cessation, pulmonary
tissue hypoxia rehabilitation

OSMOSIS.ORG 893
 CYSTIC FIBROSIS (CF)
osms.it/cystic-fibrosis
PATHOLOGY & CAUSES
▪ Autosomal-recessive multisystem disorder
▫ Affects lungs, digestive system,
reproductive system, sweat glands
▪ Caused by CFTR gene defect (located on
long arm of chromosome 7)
▫ Encodes cyclic adenosine
monophosphate–regulated chloride
channel cystic fibrosis transmembrane
conductance regulator (CFTR)
▫ Various mutations: including lack of
protein production; protein trafficking
defect, degradation within cellular
endoplasmic reticulum, Golgi body
▪ Genetic defect → impaired sodium, chloride
transport across epithelial cell surface →
thick, tenacious secretions
▫ Classic triad: ↑ sweat chloride levels,
chronic sinopulmonary disease,
pancreatic insufficiency
▪ Bronchi effects
▫ Goblet cell hyperplasia, submucosal
gland hypertrophy → production
of viscous mucus, mucus plugging
→ airway inflammation → elastase
released from neutrophils → tissue
destruction → ↑ thickness of airway
walls, bronchiectatic cysts, ventilation-
perfusion mismatch → hypoxemia
RISK FACTORS
▪ Family CF history; especially carrier parents
▪ ↑ incidence in white people of Northern,
Central European descent
COMPLICATIONS
▪ Chronic respiratory tract infections
▫ Common bacteria: Pseudomonas
aeruginosa, Staphylococcus aureus,
Haemophilus influenzae (especially
younger children)
▫ Invasive fungal disease may occur →
allergic bronchopulmonary aspergillosis
894 OSMOSIS.ORG
(ABPA)
▪ Sinusitis
▫ Related to chronic inflammation
▪ Significant hemoptysis
▫ Related to enlarged, tortuous bronchial
arteries
▪ Bronchiectasis
▫ Due to mucus plugging
▪ Pneumothorax
▫ Related to ruptured emphysematous
bullae
▪ Secondary pulmonary hypertension
▫ Related to small pulmonary artery
hypertrophy
▪ Nasal polyps
▫ Related to chronic inflammation
▪ Respiratory failure
▪ Non-pulmonary complications
▫ Cirrhosis; gallstones; pancreatitis; heat
exhaustion, dehydration; hypochloremic
alkalosis (excessive salt-loss in sweat);
rectal prolapse; infertility (azoospermia);
fat-soluble vitamin deficiency; anemia;
nail clubbing
SIGNS & SYMPTOMS
▪ Highly variable presentation
▫ Related to specific mutation, gene
penetrance, environmental factors
▪ Specific pulmonary manifestations
▫ Chronic, productive cough; dyspnea; ↑
anterior-posterior chest diameter; digital
clubbing; basilar crackle; expiratory
wheeze; generalized hyperresonance
 Chapter 126 Obstructive Lung Disease

DIAGNOSIS
DIAGNOSTIC IMAGING
Prenatal ultrasound
▪ May detect hyperechogenic bowel,
meconium peritonitis

Chest X-ray
▪ Hyperinflation, air trapping, atelectasis,
flattened diaphragm, peribronchial
thickening, bronchovascular markings,
peribronchial cuffing, parallel lines (related
thickened bronchial walls—”tram tracks”)

CT scan
▪ Inspissated bronchial secretions; detects
degree of bronchiectasis Figure 126.6 A plain chest radiograph
demonstrating tram-track opacities and ring
shadows in an individual with cystic fibrosis.
LAB RESULTS They are particularly well demonstrated in
▪ Genetic testing the left upper zone.
▪ CFTR mutation identification
▪ Sweat chloride test
▫ ↑ sweat chloride concentration
OTHER DIAGNOSTICS
▪ Newborn screening
▫ Pilocarpine administered → stimulate
sweat; collected, analyzed for chloride ▫ Detects CF in neonatal period; initiate
content early intervention
▪ Pulmonary function tests
▫ ↓ FEV1 FEV1/FVC
▫ ↑ residual volume to total lung capacity
(RV/TLC) ratio
▫ ↓ total lung capacity
▫ ↓ vital capacity

TREATMENT
MEDICATIONS
▪ CFTR modulators
▪ Medications to clear respiratory secretions;
inhaled hypertonic saline
▪ Anti-inflammatory medications (e.g.
glucocorticoids)
▪ Antibiotics
▫ Infections
Figure 126.7 A CT scan of the chest in ▪ Bronchodilators
the coronal plane demonstrating bilateral ▫ ↓ airflow obstruction
widespread bronchiectasis in a twenty five
▪ Prevention
year old female with cystic fibrosis.
▫ Annual influenza vaccine; pneumococcal
vaccine

OSMOSIS.ORG 895
 SURGERY
▪ Lung transplantation
▪ Respiratory support
▫ Respiratory failure → invasive
ventilation
EMPHYSEMA
osms.it/emphysema
PATHOLOGY & CAUSES
▪ COPD subset
▫ Exposure to irritants → degrades elastin
in alveoli, airways → air-trapping, poor
gas exchange.
▪ Irritants (e.g. cigarette smoke) →
attraction of inflammatory cells → release
leukotrienes, chemical mediators (e.g.
B4; IL8; TNF alpha/proteases, elastases/
collagenases) → destroy collagen, elastin
→ lose elasticity → low pressure during
expiration pulls walls of alveoli inward →
collapse → air-trapping distal to collapse →
septa breaks down → neighboring alveoli
coalesce into larger air spaces → decreased
surface area available for gas exchange
▫ Loss of elastin → lungs more compliant
(lungs expand, hold air)
▫ Alveolar air sacs permanently enlarge,
lose elasticity → exhaling difficult
TYPES
Centriacinar/centrilobular emphysema
▪ Most common
▪ Damage to central/proximal alveoli of
acinus sparing distal alveoli
▫ Individuals who smoke (irritants can’t
reach distal alveoli); upper lobes of lungs
Panacinar emphysema
▪ Entire acinus uniformly affected
▫ A1AT deficiency; lower lobes of lungs
896 OSMOSIS.ORG
OTHER INTERVENTIONS
▪ Address complications
▪ Chest physiotherapy
▫ Mobilize retained secretions
▪ Respiratory support
▫ Supplemental oxygen
▫ Positive-pressure ventilation
Paraseptal emphysema
▪ Distal alveoli most affected
▫ Lung tissue on periphery of lobules near
interlobular septa
▫ Ballooned alveoli on lung surface
rupture → pneumothorax
CAUSES
▪ Smoking, A1AT deficiency
COMPLICATIONS
▪ Hypoxic vasoconstriction → cor pulmonale
▫ Poor gas exchange → vessels
vasoconstrict to shunt blood to
better gas exchange → pulmonary
hypertension → increased workload
for right heart → right ventricular
hypertrophy → cor pulmonale
▪ Hypoxemia
▪ Pneumothorax
SIGNS & SYMPTOMS
▪ Barrel chest (air-trapping, hyperinflation
of lungs), apparent respiratory distress
with use of accessory muscles, tripod
positioning, weight loss, exhaling slowly
through pursed lips (“pink puffers”),
hyperventilation
▪ Pursing lips increases pressure in airway
→ keeps airway from collapsing → weight
loss
▪ Dyspnea, cough (with less sputum)
 Chapter 126 Obstructive Lung Disease

DIAGNOSIS
DIAGNOSTIC IMAGING
Chest X-ray
▪ Increased anterior-posterior diameter,
flattened diameter, increased lung field
lucency (air-trapping)

OTHER DIAGNOSTICS
▪ Increased TLC
▪ FVC decreased (esp. FEV1)

TREATMENT
MEDICATIONS
▪ Bronchodilators
▪ Inhaled steroids
▪ Combination inhalers
▫ Bronchodilators + inhaled steroids
▪ Oral steroids
▫ Adverse effects: oral candidiasis, weight
gain, diabetes, osteoporosis
▪ Antibiotics (e.g. azithromycin prevents Figure 126.8 The gross pathological
exacerbations) appearance of emphysema. There are
▪ Supplemental oxygen numerous dilated airspaces in a peripheral
distribution.

SURGERY
▪ Lung volume reduction
▫ Removal of areas of damaged lung
tissue to create extra space in chest
cavity for healthy lung tissue to expand
▫ Can improve quality of life and prolong
survival
▪ Lung transplant
▪ Bullectomy
▫ Removal of bullae (large air spaces) to
improve air flow

OTHER INTERVENTIONS Figure 126.9 The histological appearance

▪ Pulmonary rehabilitation program of emphysema There are numerous
▫ Customized education plan consisting of hyperexpanded alveoli.
exercising training, nutrition advice, and
lifestyle counseling

OSMOSIS.ORG 897
 MNEMONIC: P vs. B
Emphysema vs. Bronchitis
EmPhysema: Pink Puffer
Chronic Bronchitis: Blue
Bloater

898 OSMOSIS.ORG
 NOTES

NOTES
RESTRICTIVE LUNG DISEASE

GENERALLY, WHAT IS IT?

PATHOLOGY & CAUSES DIAGNOSIS
▪ Inflammatory disorders of lung parenchyma DIAGNOSTIC IMAGING
▪ Restricts lung expansion → decreases
High resolution chest CT scan
lung volume, ventilation, gas exchange →
difficulty breathing
LAB RESULTS
RISK FACTORS ▪ Lung biopsy
▪ Exposure to occupational, biological dusts
OTHER INTERVENTIONS
▪ Spirometry
SIGNS & SYMPTOMS ▫ ↓ Vital capacity
▫ ↓ Total lung volume
▪ Dyspnea, cough
▫ ↓ Forced expiratory volume in one
second (FEV1)
▫ ↓ Diffusion capacity of carbon monoxide
▪ Bronchopulmonary lavage

TREATMENT
SURGERY
▪ Lung transplant (definitive)

Figure 131.1 Illustration depicting the various criteria examined during a spirometric test.

OSMOSIS.ORG 935
 IDIOPATHIC PULMONARY FIBROSIS
osms.it/idiopathic-pulmonary-fibrosis
PATHOLOGY & CAUSES
▪ Abnormal pulmonary healing process:
pulmonary insult heals → excess deposits
of collagen, fibrotic tissue → progressive
scarring of lung tissue → loss of lung
compliance → dyspnea worsens, lung
function declines → hypoxemia
▪ Affects pulmonary interstitium: tissue
between alveoli, airspaces, peripheral
airways, vessels
▪ Chronic, irreversible, ultimately fatal disease
CAUSES
▪ Overproliferation of type 2 pneumocytes
→ excessive myofibroblast population
→ excessive collagen production →
collagen accumulates → interstitial layer
thickens between alveoli, capillary → poor
ventilation/gas exchange, lung parenchyma
stiffens → restricted lung expansion
(restrictive lung disease)
RISK FACTORS
▪ Ages 50–70, history of smoking, more
common in individuals who are biologically
male, exposure to occupational dusts (e.g.
metal, wood, coal, silica, stone), biologic
dusts (e.g. hay, molds, spores, agricultural
products, livestock), gastroesophageal
reflux disease, genetic
SIGNS & SYMPTOMS
▪ Worsens over time, coughing (dry non-
productive cough, worse on exertion),
dyspnea (progressive exertional), cyanosis,
digital clubbing, dry inspiratory bibasilar
crackles on auscultation, significant
respiratory failure with increasing tissue
loss
936 OSMOSIS.ORG
DIAGNOSIS
▪ Exclude known causes of interstitial lung
disease (e.g. hypersensitivity pneumonitis,
pulmonary Langerhans cell histiocytosis,
asbestosis, collagen vascular disease)
DIAGNOSTIC IMAGING
High-resolution chest CT scan
▪ Usual interstitial pneumonia (UIP) pattern
▫ Honeycombing with well-defined walls
▫ Reticular opacities with/without traction
bronchiectasis (ground glass opacities,
honeycombing, cystic spaces)
▫ Subpleural, basal lung fields
▫ Absence of features inconsistent with
UIP (mid to upper predominance;
peribronchovascular predominance;
extensive ground glass appearance;
profuse micronodules; discrete cysts
away from areas of honeycombing;
diffuse air-trapping)
▫ Bronchopulmonary consolidation
▪ Thickening of interstitial walls
▫ Fibrotic changes
▫ Bases, periphery
LAB RESULTS
Biopsy
▪ Taken from three different areas,
large enough to show underlying lung
architecture (bronchoscopic biopsies
insufficient; thoracotomy/thoracoscopy
prefered)
▪ Histology
▫ Interstitial fibrosis in patchwork
pattern; interstitial scarring; honeycomb
changes; fibroblastic foci (dense
collections of myofibroblasts, scar
tissue)
 Chapter 131 Restrictive Lung Disease

OTHER INTERVENTIONS
TREATMENT
Broncheolar lavage
▪ Cytology MEDICATIONS
▫ Exclude alternative diagnoses (e.g. ▪ Antifibrotic medication
malignancy, infection, eosinophilic ▫ Slows progression
pneumonia, histiocytosis X, alveolar ▪ Seasonal influenza vaccine
proteinosis)
▪ Lymphocytes > 30% SURGERY
▫ Exclude idiopathic pulmonary fibrosis ▪ Lung transplant (definitive)

Spirometry
▪ Restrictive pattern decreased
▫ Total lung capacity
▫ Forced vital capacity (FVC)
▫ FEV1
▪ Decreased diffusing capacity of lungs for
carbon monoxide

Figure 131.3 A CT scan of the chest in

Figure 131.2 The clinical appearance of
digital clubbing as seen in a case of idiopathic
pulmonary fibrosis.
the axial plane demonstrating marked
honeycombing of the lung and a collection
of subpleural cysts in an individual with
idiopathic pulmonary fibrosis.

OSMOSIS.ORG 937
 SARCOIDOSIS
osms.it/sarcoidosis
PATHOLOGY & CAUSES
▪ Disease involving formation of
noncaseating granulomata (clumps of
inflammatory cells)
▪ Can affect any organ system
▫ Accumulation of monocytes, epithelioid
macrophages, activated T-lymphocytes
▫ Macrophages may aggregate to
form multinucleated giant cells (AKA
Langhans giant cells)
▫ Increased production of inflammatory
mediators (Th-1 mediated)
▫ Cytokines released from activated
immune cells → systemic effects
CAUSES
▪ Unknown; may be triggered by immune
reaction in genetically predisposed
individuals
RISK FACTORS
▪ Genetic, previous episode of sarcoidosis,
biological females, 20–50 age group
COMPLICATIONS
Paradoxical effect on immune reactivity
▪ Increased macrophage and CD4
helper T-cell activation → accelerated
inflammation
▪ But antigen challenges, e.g. tuberculin skin
test are suppressed
▪ This paradoxical hyper-/hypo-activity is
immunological anergy → increased risk of
infections, cancer
Pulmonary pathology
▪ > 90% of affected individuals
▪ Bilateral hilar lymphadenopathy (up to 90%
of affected individuals)
▪ Predominantly upper lobe parenchymal
infiltration
938 OSMOSIS.ORG
▪ Airway involvement → airway
hyperresponsiveness (increased sensitivity
to inhaled triggers)
▪ Pulmonary hypertension → cor pulmonale
Ocular pathology
▪ Up to 25%
▪ Significantly more common in Asian people
of Japanese descent (>70%)
▪ Anterior uveitis
▪ Uveoparotitis (inflammation of uvea, parotid
gland)
▪ Retinitis
Cardiac pathology
▪ 5% symptomatic, autopsy reports 25–70%
subclinical involvement
▪ Significantly more common in Asian people
of Japanese descent
▪ Conduction defects
▫ Asymptomatic conduction abnormalities
▫ Fatal ventricular arrhythmias
▫ Complete heart block
▫ Sudden cardiac death
▪ Cardiac fibrosis, interstitial fluid
accumulation, heart failure, valvular
dysfunction, pericardial disease
Nervous system pathology
▪ ~5%
▪ AKA neurosarcoidosis
▪ Variable presentation
▫ Cranial nerves most commonly affected
▫ Neuroendocrine changes
▫ Chronic meningitis
Endocrine/exocrine pathology
▪ Sarcoidosis of anterior pituitary
▫ Deficiency of adrenocorticotropic
hormone, thyroid-stimulating hormone,
follicle-stimulating hormone, luteinizing
hormone, insulin-like growth factor 1
▪ Hypothalamic dysfunction
▫ Hypersecretion of prolactin
 Chapter 131 Restrictive Lung Disease

▪ Increase in 1,25-dihydroxyvitamin D (active

form of vitamin D)
▫ Hydroxylation usually occurs in
kidney; in sarcoidosis it may occur in
sarcoid granulomata due to activated
macrophages → hypercalcemia →
hypercalciuria
Hepatic pathology
▪ Liver granulomata very common (70%)
▪ Only 20–30% have detectable aberrant
liver function
▪ Liver granlomata → cholestatic pattern →
raised alkaline phosphatase, mildly elevated
bilirubin, aminotransferases
Nephrological pathology
▪ < 5%
▪ Can cause nephritis, but renal injury from
hypercalcemia more common
▪ Nephrocalcinosis, nephrolithiasis
Gynecological/Urological
▪ Uncommonly epididymis, tesicles, prostate,
ovaries, fallopian tubes, uterus or vulva may
be affected
▪ Biological males → infertility
SIGNS & SYMPTOMS
▪ Varies by organ. May be asymptomatic.
General
▪ Peripheral lymphadenopathy, fatigue (not
relieved by sleep), weight loss, arthralgia,
dry eyes
Lower respiratory manifestations
▪ Wheezing, cough, dyspnea, chest pain,
hemoptysis, crackles
Upper respiratory sarcoidosis (uncommon)
▪ Laryngeal sarcoid: involves supraglottis,
occasionally subglottis
▫ Subglottis: dysphagia, dyspnea, cough,
hoarseness
▪ Nasal and sinus sarcoidosis: nasal
obstruction, nasal crusting, anosmia,
epistaxis, nasal polyposis

Hematological
▪ Sequestration of lymphocytes into areas of
inflammation → lymphopenia
▪ Anemia
▪ Leukopenia
▫ May reflect bone marrow involvement or
redistribution of T-cells to disease sites
Figure 131.4 The clinical appearance of
▪ Monocytosis cutaneous sarcoidosis.
▪ Polyclonal hypergammaglobulinemia

Rheumatological
Skin
▪ 10%
▪ Erythema nodosum
▪ Acute polyarthritis
▫ Inflammation of subcutaneous adipose
▪ Enthesitis tissue → painful nodules
▫ Inflammation at sites where tendons or ▫ Affects anterior surface of lower
ligaments insert into bone extremities
▪ Chronic sarcoid arthritis ▪ Plaques
▫ Diffuse organ involvement ▫ Often seen in chronic forms
▫ Periosteal bone resorption ▫ Affects shoulders arms, back and
buttocks
▪ Maculopapular eruptions
▫ Common manifestation

OSMOSIS.ORG 939
 ▫ Affects alae, nares, lips, eyelids,
forehead, nape of neck, sites of previous
trauma
▪ Subcutaneous nodules
▫ Affects face, trunk, extensor surfaces
▪ Lupus pernio
▫ Violaceous or erythematous indurated
papules, plaques/nodules
▫ Primarily affects nose, cheeks, chin, ears
Ocular involvement
▪ Photophobia, blurred vision
▪ Increased tearing or dry eyes
▪ Loss of visual acuity → blindness
▪ Heerfordt syndrome: anterior uveitis,
parotitis, cranial nerve VII palsy, fever
Cardiac involvement
▪ Palpitations, dizziness, chest pain
Nervous system
▪ Hearing abnormalities, headache, altered
consciousness level, changes in peripheral
sensation
Endocrine & exocrine changes
▪ General: changes in body temperature,
mood alterations, swelling of salivary/
parotid glands
▪ Biological females: amenorrhea,
galactorrhea, nonpuerperal mastitis,
changes in menstrual cycle
▪ Biological males: hypogonadism
▪ Other clinical manifestations of
hypopituitarism, e.g. diabetes insipidus,
hypothyroidism, adrenal insufficiency
Hepatic
▪ Hepatomegaly
Nephrological
▪ Reduced creatinine clearance
▪ Proteinuria
▪ Signs and symptoms of renal calculi
940 OSMOSIS.ORG
Hematological
▪ Signs and symptoms of anemia,
immunodeficiency
▪ Splenomegaly
▪ Immunological abnormalities
▫ Allergies to test antigens, e.g. candida or
purified protein derivative
Rheumatological
▪ Acute polyarthritis
▪ Symmetric involvement of ankle joints
▪ Usually periarthritis not true arthritis
▪ May be present in isolation or as part of
Löfgren syndrome
▪ Löfgren syndrome
▫ Acute form of sarcoidosis
▫ 95% specificity for sarcoidosis
▫ Predominantly occurs in biological
females of Scandinavian, Irish, and
Puerto Rican descent
▫ Bilaterally enlarged hilar lymph nodes
▫ Erythema nodosum (tender red nodules,
typically pretibial surface)
▫ Arthritis most commonly occurring in
ankles > knees > wrists > elbows >
metacarpophalangeal joints; usually not
true arthritis, but periarthritis affecting
soft tissue around joints
▫ Enthesitis (inflammation sites where
tendons/ligaments insert into the bone)
▪ Chronic sarcoid arthritis
▫ Diffuse organ involvement
▫ Ankles, knees, wrists, elbows, hands
may be affected (polyarticular pattern)
▫ Dactylitis (inflammation of entire digit)
▫ Pain, stiffness

MNEMONIC: SARCOIDOSIS
Features of Sarcoidosis
Schaumann calcifications
Asteroid bodies/ACE increase/
Anergy
Respiratory complications/
Renal calculi/Restrictive
lung disease/Restrictive
cardiomyopathy
Calcium increase in serum and
urine/CD4 helper cells
Ocular lesions
Immune mediated
noncaseating granulomas/Ig
increase
Diabetes insipidus/D vit.
increase/Dyspnea
Osteopathy
Skin: subcutaneous nodules,
erythema nodosum
Interstitial lung fibrosis/IL-1
Seventh CN palsy
Figure 131.5 A giant cell containing an
asteroid body in a case of pulmonary
sarcoidosis.
DIAGNOSIS
▪ Diagnosis of exclusion
▪ Usually dependent on biopsy of organ
involved
Chapter 131 Restrictive Lung Disease
▫ Noncaseating granulomata
▫ Tuberculin skin test (tuberculosis,
sarcoidosis share many clinical features)
▫ Exclusion of other granulomatous
causes
DIAGNOSTIC IMAGING
X-ray, CT scan
▪ Staged according to extent of lung
involvement (Siltzbach classification
system)
▫ Stage 0: normal lung at presentation
▫ Stage I: bilateral hilar lymphadenopathy
only (60% resolution within 1–2 years)
▫ Stage II: bilateral hilar lymphadenopathy
with pulmonary infiltrates (46%)
▫ Stage III: pulmonary infiltrates without
bilateral hilar lymphadenopathy (12%)
▫ Stage IV: pulmonary fibrosis
▪ CT scan-/ultrasound-guided biopsy/fine-
needle aspiration of mediastinal lymph
nodes
▫ Flow cytometry
▫ Microscopy and staining
▫ Culture
PET scan
▪ Lamba sign → gallium uptake in
paratracheal, hilar lymph nodes
▪ Panda sign → lacrimal, parotid,
submandibular glands with normal
nasopharyngeal uptake
▪ Combination of two specific for sarcoidosis
LAB RESULTS
▪ High blood calcium (normal parathyroid
level)
▪ Elevated angiotensin converting enzyme
(level correlates with total granuloma load)
▫ Can be used for monitoring treatment
and disease progression
OTHER DIAGNOSTICS
Lung function testing
▪ Determine level of function
▪ Monitor course of disease
▪ Typically reveals restrictive pattern (reduced
vital/total lung capacity)
OSMOSIS.ORG 941
 ▪ Endobronchial sarcoid may lead to symptoms
impairment of airflow, obstructive pattern ▫ Topical/local therapy preferred for
organ-confined disease
Diffusion of carbon monoxide (DLCO)
▪ Most sensitive test for interstitial lung
disease MEDICATIONS

Bronchoscopy Anti-inflammatory drugs

▪ Biopsy ▪ NSAIDS
▪ Bronchoalveolar lavage ▫ Up to 75% of individuals may achieve
sufficient symptomatic control on these
▫ CD4/CD8 T cell ratio in bronchoalveolar
alone
lavage is raised > 3.5 (can be normal/
low) ▪ Corticosteroids
▫ If long course required, consider steroid-
Ophthalmological exam sparing agents
ECG Antimetabolites
▪ Methorexatem, chloroquine, azathioprine

Immunosuppressants
TREATMENT ▪ Cyclophosphamide, cladribine,
chlorambucil, cyclosporine
▪ May resolve spontaneously over years
▪ Anti-tumor necrosis factor treatment
▪ Dermatological involvement typically
resolves without treatment ▫ These agents have also been reported
to cause sarcoidosis-like illness
▪ Acute disease
▫ No therapy is a viable option for mild

Figure 131.6 The histological appearance of pulmonary sarcoidosis. There are large numbers of
giant cells visible.

942 OSMOSIS.ORG
 NOTES

NOTES
SLEEP–RELATED RESPIRATORY
DISEASE

GENERALLY, WHAT IS IT?

snoring, airflow, end tidal CO2, oxygen
PATHOLOGY & CAUSES saturation, cardiac rhythm, body positioning
▫ Electroencephalography: sleep pattern
▪ Impaired capacity to breathe
▫ Electrooculography: REM
▫ Electromyography: neck muscle tonicity
SIGNS & SYMPTOMS ▫ Electrocardiography: heart rhythm
▫ Video monitoring: body positioning
▪ Apneic episodes (variable duration); fatigue;
hypoxemia; hypercapnia
TREATMENT
DIAGNOSIS OTHER INTERVENTIONS
▪ Supportive, lifestyle modification
OTHER DIAGNOSTICS
Polysomnography
▪ Measure sleep patterns, rapid eye
movements (REM), tonicity of neck muscles,

APNEA OF PREMATURITY
osms.it/apnea-of-prematurity
CAUSES
PATHOLOGY & CAUSES ▪ Immaturity of fetal brain areas responsible
for breathing
▪ Most common cause of apnea in preterm
▪ Incidence increases with degree of
neonates
prematurity
▪ Developmental disorder associated with
▫ Most neonates < 28 weeks GA
decreased responsiveness to carbon
dioxide ▫ > ½ neonates 28–36 weeks GA
▪ Respiratory pauses of ≥ 20 seconds/shorter
pause with bradycardia (< 100/minute),
cyanosis, pallor, oxygen desaturation in
SIGNS & SYMPTOMS
neonates < 37 weeks gestational age (GA)
▪ Apneic episodes ≥ 20 seconds in first 72
hours post-birth
▫ Frequency increases 14–21 days post-
birth

OSMOSIS.ORG 943
 ▪ Bradycardia
▪ Hypoxemia
TREATMENT
▪ Resolves spontaneously after 37 weeks
DIAGNOSIS postmenstrual age
▫ Postmenstrual age = postnatal age +
OTHER DIAGNOSTICS GA age
▪ Monitor premature neonates
▫ Cardiorespiratory monitors, pulse MEDICATIONS
oximetry ▪ Methylxanthines
▪ Exclude other causes for apnea ▫ Improve sensitivity to carbon dioxide,
▫ Metabolic disorders, neurological increase ventilations/minute, decrease
disorders, infections, antepartum drugs periodic breathing events
(e.g. opiates)
OTHER INTERVENTIONS
▪ Nasal CPAP

SLEEP APNEA
osms.it/sleep-apnea
second apnea → individual wakes from
PATHOLOGY & CAUSES sleep
▪ Most common form of sleep apnea;
▪ Irregular breathing patterns, shallow peripheral problem; obstruction at
breathing and snoring during sleep. oropharynx
▪ Apnea: momentary: pause in breathing
▪ Can last several seconds to several minutes
CAUSES
▪ More than five episodes an hour must occur
▪ Hypopnea: abnormally shallow breathing Obstructive sleep apnea
event ▪ Obesity (most common)
▪ Hypertrophic adenoid glands/palatine
TYPES tonsils
▪ Micrognathia (small chin, AKA underbite)
Central sleep apnea ▪ Sedatives (excessive muscle relaxation—
▪ Sudden failure of brain respiratory center’s alcohol, sleeping pills)
generation of spontaneous breathing ▪ Allergies
efforts
▪ Hypothyroidism (obesity, less muscle tone)
▪ Damage to brain respiratory centers→
↑ respiratory drive → hyperventilation
→ CO2 (hypocapnia) → apnea → ↑ ↑ RISK FACTORS
CO2(hypercapnia) → ↑ respiratory drive → ▪ More common in individuals who are
hyperventilation biologically male
▪ Associated with Cheyne–Stokes respiration ▪ Incidence increases with age

Obstructive sleep apnea

▪ Intermittent airway obstruction → 20–30

944 OSMOSIS.ORG
 Chapter 132 Sleep-Related Respiratory Disease

COMPLICATIONS
DIAGNOSIS
Obstructive sleep apnea
▪ Systemic hypertension OTHER DIAGNOSTICS
▪ Diabetes ▪ Polysomnography
▪ Anginal chest pain, arrhythmias, heart
failure
▪ Pulmonary hypertension, cor pulmonale,
TREATMENT
respiratory failure
MEDICATIONS
▪ Central sleep apnea: respiratory stimulants
SIGNS & SYMPTOMS (acetazolamide, theophylline)

▪ Sleep deprivation, excessive daytime SURGERY

fatigue ▪ Obstructive sleep apnea: micrognathia,
▪ Headache, difficulty concentrating hypertrophic adenoids/tonsils
▪ Morning headaches

Central sleep apnea OTHER INTERVENTIONS

▪ Nocturia ▪ Continuous positive airway pressure
(CPAP)
▪ Stress-induced insomnia
▪ Central sleep apnea: supplemental oxygen
▪ Nocturnal anginal chest pain
during sleep
Obstructive sleep apnea ▪ Obstructive sleep apnea: custom
▪ Loud snoring mouthpieces, weight loss
▪ Hypopnea
▪ Repeated arousals from sleep
▪ Decreased libido

Figure 132.1 A CT scan of the head and

neck in the sagittal plane. The soft palate is
elongated, thickened and abutts the posterior
pharynx, leading to obstructive sleep apnea.

OSMOSIS.ORG 945

PNEUMOCYSTIS JIROVECII
(PNEUMOCYSTIS PNEUMONIA)
osms.it/pneumocystis-jirovecii
PATHOLOGY & CAUSES
▪ Opportunistic yeast-like fungi (originally
classified as protozoan) responsible for
pneumocystis pneumonia
▪ Formerly known as Pneumocystis carinii
▪ Airborne transmission route; human-to-
human route occurs early in life
▪ Immunocompetent individuals may act as
asymptomatic reservoirs
▪ 5–7 micrometer cysts contain up to eight
pleomorphic intracystic sporozoites →
become excysted → form trophozoites
▪ Reside in alveoli
▪ Disease: pneumocystis pneumonia
▫ Occurs exclusively in
immunocompromised individuals
▫ Remains localized in lungs
▫ Clinical manifestations due to
inflammatory reaction in alveoli lumen/
septum
▫ Fatal if left untreated
Figure 84.7 A foamy alveolar cast in a
bronchial washing taken from an individual
with Pneumocystis pneumonia.
Chapter 84 Opportunistic Fungal Infections
RISK FACTORS
▪ Defects in cell-mediated immunity, HIV/
AIDS, severe combined immunodeficiency
syndrome, hematological malignancies,
transplant recipients, hyper IgM syndrome
SIGNS & SYMPTOMS
▪ Most infections asymptomatic in
immunocompetent individuals
▪ Abrupt onset of tachypnea, fever, cough
▪ Respiratory distress
DIAGNOSIS
DIAGNOSTIC IMAGING
Chest X-ray/CT scan
▪ Diffuse, bilateral ground glass opacities
▪ First appearing in perihilar area →
progresses peripherally, apical regions
spared
LAB RESULTS
▪ Microscopic examination with silver stain
▫ Disc-shaped yeast
▪ Open lung biopsy
▪ Bronchoalveolar lavage
▪ PCR of sputum/lavage samples
▪ ↓ PaO2 (reflects severity of disease)
▪ Unchanged WBC count
TREATMENT
MEDICATIONS
▪ Trimethoprim-sulfamethoxazole
▪ Alternatives
▫ Pentamide, dapsone + trimethoprim,
atovaquone
OSMOSIS.ORG 469
 ▪ Prophylactic trimethoprim-
sulfamethoxazole/pentamide
▫ Individuals with HIV, < 200 CD4+ cells/
mm3
OTHER INTERVENTIONS
▪ Respiratory support
SPOROTHRIX SCHENCKII
osms.it/sporothrix-schenckii
PATHOLOGY & CAUSES
▪ Chronic subcutaneous thermally dimorphic
fungus → sporotrichosis
▪ Found in soil, decomposing vegetation,
plant materials (e.g. moss, hay, wood, rose
bushes)
▪ Found worldwide, mostly in temperate/
tropical regions (16–22ºC/60.8–71.6°F)
▪ Outside human body grows as filamentous
mold; in tissue grows as small budding
yeast cells
Diseases
▪ Lymphocutaneous sporotrichosis
▫ Follows traumatic inoculation of skin/
subcutaneous tissue (e.g. minor insult
from thorns or splinters) → incubation
1–4 weeks → papule develops at site
of inoculation → ulceration of primary
lesion → nonpurulent, odorless drainage
→ similar lesions occur along lymphatic
channel proximal to primary lesion
▪ Pulmonary sporotrichosis
▫ Following inhalation of Sporothrix
conidia
▫ May progress to disseminated disease
470 OSMOSIS.ORG
Figure 84.8 A bronchial wash stained with
Grocott’s methenamine silver highlighting
Pneumocystis spores.
▪ Osteoarticular sporotrichosis
▫ Most commonly affected joints: knee,
elbow, wrist, ankle
▫ Chronic infection with progressive
decreased range of motion, pain,
swelling
▪ Meningeal sporotrichosis
▫ Rare, mostly in individuals with cellular
immune defects (e.g. lymphoma, AIDS)
▫ Chronic course
▪ Disseminated cutaneous sporotrichosis
▫ Rare (< 1%)
▫ Numerous small papules/vesicles →
necrotic, ulcerated nodules on trunk,
limbs
▫ Follows lymphatic spread
RISK FACTORS
▪ Lymphocutaneous
▫ Exposure due to skin trauma (e.g. living
in homes with dirt floors)
▫ Individual with outdoor preoccupation
▫ Contact with cats
▪ Pulmonary
▫ Chronic obstructive pulmonary disease
(COPD)
▪ Excessive alcohol use
 LAMBERT–EATON MYASTHENIC
SYNDROME (LEMS)
osms.it/lambert-eaton-myasthenic
PATHOLOGY & CAUSES
▪ Rare autoimmune disorder
▫ Autoantibodies inhibit presynaptic
calcium channels on motor neurons
→ reduced acetylcholine release in
neuromuscular junction
▪ Muscle weakness
▫ Improves temporarily after repeated
muscle use (no significant muscle
atrophy)
▪ Mostly affects somatic nervous system,
can also affect autonomic nervous system’s
parasympathetic part
▪ Middle-aged adults (most cases)
CAUSES
Type II hypersensitivity reaction
▪ B cells produce antibodies that target, block
voltage-gated calcium channels located
presynaptically on motor neurons → only
few unbound channels available to open,
allow calcium in → ↓ calcium within neuron
(insufficient to trigger acetylcholine release)
→ ↓ acetylcholine release in neuromuscular
junction → attached muscle fiber does not
contract
▪ Repeated stimulation by brain’s electrical
impulses → enough calcium might get
through remaining unbound calcium
channels → acetylcholine release → muscle
contraction
RISK FACTORS
▪ Malignancy
▫ Strong small-cell lung cancer
association; stimulus for antibody
production is same calcium channel
expression in neoplastic cells
▫ Other associated malignancies include
662 OSMOSIS.ORG
lymphoproliferative disorders (e.g.,
Hodgkin’s lymphoma)
▪ Autoimmune diseases
▫ Hashimoto’s thyroiditis, diabetes
mellitus type 1, vitiligo
COMPLICATIONS
▪ Respiratory muscle involvement →
respiratory failure
▪ Underlying malignancy → can lead to death
SIGNS & SYMPTOMS
▪ Progressive, symmetrical proximal muscle
weakness (e.g., shoulders, hips, thighs) →
difficulty climbing stairs/standing when
seated
▫ Paraneoplastic LEMS: more rapidly
progressive course
▪ Warming-up phenomenon
▫ Repeated muscle use → weakness
temporarily relieved
▪ Reflex strength ↓
▫ Muscle activation → reflex recovery/
improvement
▪ Small minority
▫ Ocular, oropharyngeal muscle
involvement
▪ Advanced stages
▫ Possible respiratory muscles
involvement → respiratory failure
(myasthenic crisis)
▪ Autonomic symptoms
▫ Dry mouth (most common),
constipation, blurry vision, erectile
dysfunction, urinary problems, syncope

DIAGNOSIS
DIAGNOSTIC IMAGING
CT scan
▪ Chest
▫ Detect underlying small-cell lung cancer
▪ Abdomen, pelvis also recommended
▪ Negative initial malignancy evaluation
▫ Periodical screening recommended
LAB RESULTS
▪ Serological tests
▫ Detect antibodies against the voltage-
gated calcium channels
OTHER DIAGNOSTICS
▪ Electrophysiologic studies
▫ Repetitive nerve stimulation: ↑ muscle
action potential amplitude
▫ Electromyogram: ↑ muscle action
potential amplitude after exercise
▪ PFT
▫ ↓ FVC → respiratory muscle
involvement
MYASTHENIA GRAVIS
osms.it/myasthenia-gravis
PATHOLOGY & CAUSES
▪ Autoimmune disorder; significant skeletal
muscle weakness
▫ Decreased acetylcholine receptor
function → worsens with muscle use
▫ Most common neuromuscular junction
disorder
▪ Type II hypersensitivity reaction
▫ B cells produce antibodies against
postsynaptic nicotinic acetylcholine
receptors of neuromuscular junction/
receptor-associated proteins
▫ Autoantibodies targeted against
muscle-specific receptor tyrosine kinase
Chapter 85 Neuromuscular Junction Disorders
TREATMENT
MEDICATIONS
▪ Symptomatic therapy
▫ Acetylcholinesterase inhibitors: minimal
effect
▫ Aminopyridines: block potassium
channels → prolonged nerve membrane
depolarization → ↑ calcium entry → ↑
acetylcholine release in neuromuscular
junction
▪ If above methods fail
▫ Immunomodulating agents can
be used (corticosteroids, other
immunosuppressive agents)
OTHER INTERVENTIONS
▪ Occasionally treated with IVIG/
plasmapheresis
▫ More severe cases
(MuSK) → ↓ in acetylcholine receptor
function
▪ Acetylcholine cannot bind → normal action
potentials cannot be generated (adjacent
muscle
▪ Complement activated → inflammatory
response initiation → postsynaptic
membrane damage → acetylcholine
receptor destruction
▪ Bimodal onset age
▫ 20–30 years old (biologically-female
predominance)
▫ 60–70 years old (biologically-male
predominance)
▪ Associated with thymic abnormality;
thymus considered antigen source
OSMOSIS.ORG 663
 promoting autoantibody production (most
cases)
▪ Neonatal myasthenia gravis
▫ Transient myasthenia form (newborn
from individual with myasthenia gravis)
▫ Maternal antibodies → transplacental
passage → neuromuscular junction
function interference
▪ Rare non-immune mediated forms
▫ E.g. congenital myasthenia gravis
▫ Mutations affecting neuromuscular
transmission
COMPLICATIONS
▪ Myasthenic crisis
▫ Decreased respiratory muscle function
→ life-threatening respiratory failure
(requires mechanical ventilation)
▫ Occurs spontaneously/precipitated
(e.g. surgery, infection, medication,
immunosuppressive-agent withdrawal)
SIGNS & SYMPTOMS
▪ Fluctuating muscle weakness
▫ Exacerbated by repetitive muscle use
throughout day/after exertion/repetitive
movement
▪ Improves with rest
▪ Progression
▫ Symptoms continuously present,
fluctuate from mild–severe
▪ Sensation, reflexes preserved
Clinical MG forms
▪ Ocular myasthenia
▫ Limited (eyelid, extraocular muscle);
individuals (50%) with ocular
myasthenia will → generalized
myasthenia (< two years)
▪ Generalized myasthenia
▫ Ocular, bulbar, facial, limb, respiratory
muscle
▪ Ocular muscles
▫ Eyelid (ptosis), extraocular (binocular
diplopia)
▪ Bulbar muscle
▫ Jaw closure (prolonged chewing →
weakness), oropharyngeal (dysarthria,
664 OSMOSIS.ORG
dysphagia), palatal (nasal tone,
prolonged speech → hypophonia)
▪ Facial muscle
▫ Facial weakness, facial expression loss
▪ Neck muscle
▫ Cannot keep head up (“drooped head
syndrome”)
▪ Limb muscle
▫ Proximal, asymmetric muscle weakness
▪ Respiratory muscle
▫ Respiratory failure (myasthenic crisis)
DIAGNOSIS
DIAGNOSTIC IMAGING
CT scan
▪ Chest scan to detect associated thymic
abnormalities
▫ Abnormal thymus (most cases)
▫ Thymoma
LAB RESULTS
▪ Serologic test
▫ Acetylcholine receptor antibodies
(AChR-Abs)/muscle-specific receptor
tyrosine kinase antibodies (MuSK-Abs)
▫ Most specific tests
▫ Seronegative for AChR-Abs, MuSK-Abs
OTHER DIAGNOSTICS
▪ Electrophysiologic studies
▫ Repetitive nerve stimulation studies:
progressive decline in muscle action
potential amplitude (decremental
response)
▫ Single-fiber electromyography:
increased jitter
▪ Tensilon test
▫ Edrophonium: acetylcholinesterase
inhibitor with rapid onset, short acting
duration
▫ Prolongs acetylcholine presence in
neuromuscular junction → marked
improvement
▫ Easy to perform/limited utility;
high false-positive rate, possible
complications from muscarinic effects
 Chapter 85 Neuromuscular Junction Disorders

(especially older adults, e.g. bradycardia, SURGERY

bronchospasm)
▪ PFTs
▫ Periodical FVC monitoring; FVC ↓
reveals respiratory muscle involvement
▪ Ice pack test
▫ Ice pack application (2–5 minutes) →
MG-affected muscles
▫ Neuromuscular transmission
improvement in low temperature
▪ Thymectomy, especially for thymoma;
myasthenia often improves/disappears
▪ Rapidly worsening myasthenia/myasthenic
crisis
▫ Intubation
▫ Plasmapheresis/intravenous
immunoglobulin (IVIG)
▫ Long-acting immunotherapy (e.g.,
corticosteroids, azathioprine)

MNEMONIC
Edrophonium vs.
pyridostigmine
eDrophonium for Diagnosis
pyRIDostigmine is to get RID
of symptoms

Figure 85.1 A biologically-female individual

with myasthenia gravis demonstrating ptosis
of the right eye before treatment (above) and
after treatment (below) with edrophonium.

TREATMENT
▪ No curative method

MEDICATIONS
▪ Avoid MG-exacerbating drugs (e.g.
aminoglycosides, tetracyclines, beta-
blockers, quinidine)
▪ Acetylcholinesterase inhibitors
▫ Symptomatic therapy
▪ Immunomodulating agents ↓ autoantibody
production
▫ Individuals with poor
acetylcholinesterase inhibitor response
▪ Corticosteroids, other immunosuppressive
agents

OSMOSIS.ORG 665