CARDIOPULMONARY PATHOPHYSIOLOGY
OBSTRUCTIVE LUNG DISEASES
GERALD JAY GERONAN
MARCH 13, 2021
I. CHRONIC OBSTRUCTIVE PULMONARY DISEASE
• Chronic obstructive pulmonary disease is a preventable and
treatable disease state characterized by airflow limitation
that is not fully reversible
• The airflow limitation is usually progressive, is associated
with an abnormal inflammatory response of the lungs to
noxious particles or gases, and is primarily caused by
cigarette smoking.
• Although COPD affects the lungs, it also produces significant
systemic consequences. (American Thoracic Society)
• In patients with COPD, both chronic bronchitis and
emphysema are present. However, the relative contribution
of each to the disease process is often difficult to discern.
A. CHRONIC BRONCHITIS
• Chronic bronchitis is defined clinically as chronic productive
cough for 3 months in each of 2 successive years in a patient
in whom other causes of productive chronic cough have
been excluded.
• The ATS definition for chronic bronchitis is based on the
major clinical manifestations associated with the disease
(i.e., productive cough).
• GOLD explains that chronic bronchitis is defined as the
presence of cough and sputum production for at least 3
months in each of 2 consecutive years (i.e., clinical
manifestations), and is not always associated with airflow
limitation.
i. ANATOMIC ALTERATIONS OF THE LUNGS
ASSOCIATED WITH CHRONIC BRONCHITIS
• The conducting airways (particularly the bronchi) are the
primary structures that undergo change in chronic bronchitis.
As a result of chronic inflammation, the bronchial walls are
narrowed by vasodilation, congestion, and mucosal edema.
• This condition is often accompanied by bronchial smooth
muscle constriction. In addition, continued bronchial irritation
causes the submucosal bronchial glands to enlarge and the
number of goblet cells to increase, resulting in excessive
mucus production.
• The number and function of cilia lining the tracheobronchial
tree are diminished, and the peripheral bronchi are often
partially or totally occluded by inflammation and mucus
plugs, which in turn leads to hyperinflated alveoli.
• Major pathologic or structural changes are associated with
chronic bronchitis:
o Chronic inflammation and thickening of the walls of the
peripheral airways
o Excessive mucous production and accumulation
o Partial or total mucous plugging of the airways
o Smooth muscle constriction of bronchial airways
(bronchospasm) – a variable finding
o Air trapping and hyperinflation of alveoli may occur in
late stages
B. EMPHYSEMA
• Emphysema is defined pathologically as the presence of
permanent enlargement of the air spaces distal to the
terminal bronchioles, accompanied by destruction of
bronchiole walls and without obvious fibrosis.
• Note that the ATS definition for emphysema is based on the
pathology, or the anatomic alterations of the lung associated
with the disorder.
• GOLD also points out that emphysema is defined as
destruction of the alveoli and is a pathologic term (i.e.,
anatomic alteration of the lung) that is sometimes—and
incorrectly—used to describe only one of several structural
abnormalities present in patients with COPD.
i. ANATOMIC ALTERATIONS OF THE LUNGS
ASSOCIATED WITH EMPHYSEMA
• Emphysema is characterized by a weakening and
permanent enlargement of the air spaces distal to the
terminal bronchioles and by destruction of the alveolar walls.
• As these structures enlarge and the alveoli coalesce, many
of the adjacent pulmonary capillaries are also affected, and
this results in a decreased surface area for gas exchange
across the alveolar-capillary membrane.
• The distal airways, weakened in the process, tend to
collapse during expiration in response to increased
intrapleural pressure. This traps gas in the alveoli.
• The major pathologic or structural changes associated with
emphysema:
o Permanent enlargement and destruction of the air
spaces distal to the terminal bronchioles
o Destruction of the alveolar-capillary membrane
o Weakening of the distal airways, primarily the
respiratory bronchioles
o Air trapping and hyperinflation
ii. TYPES
1. Panacinar Emphysema, or Panlobular Emphysema
• There is an abnormal weakening and enlargement of all
alveoli distal to the terminal bronchioles, including the
respiratory bronchioles, alveolar ducts, alveolar sacs, and
alveoli – the entire acinus is affected by dilation and
destruction. The alveolar-capillary surface area is
significantly decreased.
• It is commonly found in the lower parts of the lungs and is
sometimes associated with a deficiency of the protease
inhibitor alpha 1-antitrypsin.
• It is one of the more severe types of emphysema and
therefore the most likely to produce significant clinical
manifestations.
2. Centriacinar Emphysema or Centrilobular Emphysema
• The pathology involves the respiratory bronchioles in the
proximal portion of the acinus,
• The respiratory bronchiolar walls enlarge, become confluent,
and are then destroyed. A rim of parenchyma remains
relatively unaffected
• Centriacinar emphysema is the most common form of
emphysema and is strongly associated with cigarette
smoking and with chronic bronchitis
C. RISK FACTORS
1. Genes – Alpha 1-antitrypsin deficiency (a.k.a alpha1-
proteinase inhibitor deficiency, A1AD, AATD, ATT
deficiency, AP1 deficiency, and alpha-1 inherited
emphysema) is a genetic disorder affecting the lung, liver,
and rarely, the skin.
2. Age – As a person ages, the risk of COPD increases.
3. Lung Growth and Development – Any condition that
affects lung growth during gestation and childhood
4. Exposure to Particles
a. Tobacco smoke - cigarette smoking is the most
commonly encountered risk factor for COPD worldwide.
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 b. Occupational exposure - organic and inorganic dusts Emphysema “Pink Puffers”
and chemical agents and fumes (e.g., asbestos, coal
dust, moldy hay, bird droppings, or paints)
c. Indoor air pollution - wood, animal dander and dung,
crop residues, and coal, commonly burned in open fires
or poorly functioning stoves, may lead to very high
levels of indoor pollution.
d. Outdoor air pollution - although high levels of air
pollution are known to be harmful to individuals with
existing heart and lung disease, the role of outdoor
pollution in causing COPD is unclear.
5. Socioeconomic status - Poverty is clearly a risk factor for
COPD
6. Asthma/Bronchial Hyperreactivity - Asthma may be a risk
factor for the development of COPD
7. Chronic Bronchitis - May be a risk factor for the
development of COPD as it may lead to emphysema
8. Respiratory Infections - history of severe childhood
respiratory infections are associated with decreased lung D. CLINICAL MINIFESTATIONS
function and increased respiratory complications in
• Increased respiratory rate (stimulation of peripheral
adulthood. Susceptibility to respiratory infections may lead to
chemoreceptors/anxiety)
COPD
9. Tuberculosis - has been shown to be a risk factor for • Increased heart rate (pulse), CO, BP
COPD • Increased AP chest diameter
• Pursed-lip breathing – helps control shortness of breath
Chronic Bronchitis “Blue Bloather” • Use of accessory muscles
• Chest assessment findings:
o Decreased tactile and vocal fremitus
o Hyperresonant percussion note
o Diminished breath sounds
o Diminished heart sounds
o Crackles/rhonchi/wheezing
• ABG: pH  PaCO2  HCO3  PaO2 
• Cyanosis
• Polycythemia, Cor pulmonale
• Cough, sputum production & Hemoptysis
• CXR – Translucent/dark lung fields, Depressed or flattened
diaphragms, long and narrow heart; enlarged heart

E. DIAGNOSIS AND ASSESSMENT

• According to GOLD, the diagnosis of COPD should be
considered for any patient who is over 40 years of age and
who has dyspnea, chronic cough or sputum production,
and/or a history of exposure to risk factors for the disease
especially cigarette smoking.

Pulmonary Function Testing – required to confirm the airflow

limitation
• FVC
• FEV1
• FEV1/FVC Ratio

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 • An FEV1/FVC ratio of less than 0.70 usually indicates the o A worsening FEV1 increases the occurrence of
presence of airway obstruction exacerbations in COPD patients and risk of death
A diagnosis of COPD is made when the patient demonstrates: • Comorbidities
• any combination of the COPD indicators o Diseases commonly associated with COPD include
• an FEV1/FVC ratio of less than 0.70 and an FEV1 less than cardiovascular disease, osteoporosis, depression and
80% anxiety, skeletal muscle dysfunction, the metabolic
• there is no alternative explanation for the symptoms and syndrome, and lung cancer.
airflow obstruction
Other important PFT values associated with COPD: Distinguishing Marks: Bronchitis vs. Emphysema
• Decreased inspiratory capacity (IC) and vital capacity (VC) FEATURES BRONCHITIS EMPHYSEMA
• Increased total lung capacity (TLC), function residual Age 40-50 60-70
capacity (FRC), and residual volume (RV), and residual Body Towards fat Thin
volume/total lung capacity ratio (RV/TLC) – these PFT Cough Considerable Negligible
values confirm alveolar hyperinflation Chest Rales/ronchi Quiet
• The carbon monoxide diffusing capacity (DLCO) decreases Dyspnea Variable Slow
in proportion to the severity of emphysema. The DLCO is Sputum Productive Scanty
normal in pure chronic bronchitis. Blood gases Hypercapnia & Normal until late
hypoxemia
F. SEVERITY ASSESSMENT Appearance Blue bloaters Pink Puffers
• The primary goals of COPD assessment are to determine
o The severity of the diseases II. ASTHMA
o The impact the disease has on the patient’s health • Asthma is described as a lung disorder characterized by
status 1) reversible bronchial smooth muscle constriction
o The risk of future events – number of exacerbation and 2) airway inflammation, and
hospital admissions, and death 3) increased airway responsiveness to an assortment of
• Symptoms Evaluation – there are several validated stimuli
questionnaires available to assess symptoms in patients • The airway mucosa becomes infiltrated with eosinophils and
with COPD other inflammatory cells, which in turn causes airway
1. COPD Assessment Test (CAT) – CAT is an eight-item inflammation and mucosal edema.
one-dimensional assessment of health status in COPD • Charcot-Leyden crystals are formed from the breakdown of
2. Modified British Medical Research council (mMRC) or eosinophils in patients with allergic asthma
Breathlessness Scale - relates well to other health • The airways become filled with thick, whitish, tenacious
conditions and predicts future mortality risks mucus.
• As a result of smooth muscle constriction, bronchial mucosal
edema, and excessive bronchial secretions, air trapping and
alveolar hyperinflation develop
• If chronic inflammation develops over time, these anatomic
alterations become irreversible, resulting in loss of airway
caliber
• Major pathologic or structural changes observed during an
asthmatic episode are as follows:
o Smooth muscle constriction of bronchial airways
(bronchospasm)
o Excessive production of thick, whitish bronchial
secretions
o Mucous plugging
o Hyperinflation of alveoli (air trapping)
o In severe cases, atelectasis caused by mucous
plugging
o Bronchial wall inflammation leading to fibrosis (in
severe cases, caused by remodeling)

i. Risk Factors
Severity assessment based on degree of airflow limitation
HOST/ INTRINSIC FACTORS
• Genetics
1) the production of allergen specific immunoglobulin E
(IgE) antibodies,
2) airway hyperresponsiveness,
3) inflammatory mediators, and
4) T-helper cells (Th1 and Th2), which are an important
part of the immune system.
• Obesity
o Asthma is more commonly seen in obese people
• Sex/ Gender
o Before the age of 14 years, the prevalence of asthma is
nearly two times greater in boys than in girls
o n adulthood, the prevalence of asthma is greater in
women than in men.
ENVIRONMENT/ EXTRINSIC FACTORS
• Risk of exacerbations • Allergens
o An exacerbation of COPD is defined as an acute event, o Outbreaks of asthma exacerbations have been reported
characterized by a worsening of the patient’s respiratory in areas of increased levels of air pollution
symptoms, that is beyond normal day-to-day variations
and leads to a change in medication
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 • Infections ii. CLINICAL MANIFESTATIONS
o Bacterial, viral upper and lower airway infections are • There are many signs and symptoms that should increase
more likely to contribute to asthma the suspicion of asthma. These include wheezing and a
• Tobacco smoke history of any of the following:
o Exposure to tobacco is associated with a greater risk of o Recurrent cough
developing asthma o Recurrent wheeze
• Diet o Recurrent difficult breathing
o infants given formulas of intact cow’s milk or soy protein o Recurrent chest tightness
have a higher incidence of wheezing symptoms in early
childhood compared with infants given breast milk
OTHERS
• Drugs - Asthma exacerbations are associated with the
ingestion of aspirin and other nonsteroidal anti-inflammatory
drugs (NSAIDs)
• Food Additives and preservatives – Sulfites have often
been associated with causing severe asthma exacerbations.
• Exercise-Induced Bronchoconstriction – Asthma is
sometimes associated with vigorous exercise. In children,
exercise is a common trigger of asthma symptoms.
• Gastroesophageal reflux – or regurgitation, appears to
significantly contribute to bronchoconstriction in some
patients
• Sleep (nocturnal asthma) – Patients with asthma often
have more breathing difficulty late at night or in the early
morning as serum cortisol levels drop at night
• Emotional Stress – In some patients, the exacerbation of
asthma appears to correlate with emotional stress and other
psychological factors
• Perimenstrual asthma – Clinical manifestations associated
with asthma often worsen in women during the premenstrual
and menstrual periods. Premenstrual asthma correlates with
the late luteal phase of ovarian activity, the phase during
which circulating progesterone and estrogen levels are low.
• Allergic bronchopulmonary aspergillosis (ABPA) –
characterized by an exaggerated response of the immune
system—a hypersensitivity response—to the Aspergillus
fungus associated in patients with asthma and cystic fibrosis. iii. DIAGNOSIS
ABPA can cause airway inflammation and bronchospasm
• Diagnosis of asthma in early childhood is based primarily on
the assessment of the child’s symptoms and physical
findings—and good clinical judgment.
• In the older child and the adult, a complete history and
physical examination—along with the demonstration of
reversible and variable air-flow obstruction—will in most
cases confirm the diagnosis of asthma.
• In the elderly patient, asthma is often undiagnosed because
of the presence of comorbid diseases that complicate the
diagnosis.
• GINA provides general guidelines to help in the clinical
diagnosis of asthma, which are based on the patient’s
symptoms and medical history. There are many signs and
symptoms that should increase the suspicion of asthma:
o Recurrent cough
o Recurrent wheeze
o Recurrent difficult breathing
o Recurrent chest tightness
• Other indicators are the occurrence or worsening of
symptoms at night or in a seasonal pattern. The presence of
eczema, hay fever, or a family history of asthma or atopic
disease may also be an indicator. Another sign is if an
individual has colds that “go to the chest” or that take more
than 10 days to clear up.

iv. DIAGNOSIS AND MONITORING

• FEV1: An increase in FEV1 of ≥12% (or ≥200 mL) after
administration of a bronchodilator suggests reversible air-
flow limitation consistent with asthma.
• FEV1/FVC ratio: Normally, the FEV1/FVC ratio is greater
than 0.75 to 0.80. Any value less than these values indicates
air-flow limitation, and asthma should be suspected.
• PEFR: An improvement of 60 L/min (or ≥20% of the
prebronchodilator [PEFR] after inhalation of a
bronchodilator), or diurnal variation in PEFR of more than
20%, suggests a diagnosis of asthma.

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 III. BRONCHIECTASIS ii. CAUSES
• Characterized by chronic dilation and distortion of one or
more bronchi—usually as a result of extensive inflammation Category Specific Examples Diagnostic Tests
and destruction of the bronchial wall cartilage, blood vessels, Acquired Bronchial Obstruction
elastic tissue, and smooth muscle components. Foreign-body Peanuts; chicken bone; Chest imaging;
• Bronchiectasis is commonly limited to a lobe or segment and aspiration teeth fiberoptic
is frequently found in the lower lobes. bronchoscopy
• Because of bronchial wall destruction, normal mucociliary Tumors Laryngeal Chest imaging;
clearance is impaired papillomatosis; airway fiberoptic
o Results in the accumulation of copious amounts of adenoma; bronchoscopy
bronchial secretions and blood that often become foul- endobronchial teratoma
smelling because of secondary colonization with Hilar adenopathy Tuberculosis; PPD; chest
anaerobic organisms. histoplasmosis; imaging;
• Thoracic infection and irritation may lead to secondary sarcoidosis fiberoptic
bronchial smooth muscle constriction and fibrosis. bronchoscopy
• The small bronchi and bronchioles distal to the affected COPD Chronic bronchitis Pulmonary
areas become partially or totally obstructed with secretions. function tests
• This condition leads to one or both of the following anatomic Rheumatic Relapsing polychondritis Clinical
alterations: disease (RP); tracheobronchial syndrome of
1) hyperinflation of the distal alveoli as a result of Amyloidosis RP/cartilage
expiratory check valve obstruction biopsy; biopsy
2) atelectasis, consolidation, and fibrosis as a result of for amyloid
complete bronchial obstruction. Mucoid Allergic Total and
• The major pathologic or structural changes associated with impaction bronchopulmonary aspergillus
bronchiectasis: aspergillosis; specific IgE;
o Chronic dilation and distortion of bronchial airways bronchocentric specific
o Excessive production of often foul-smelling sputum granulomatosis (BG); aspergillus IgG;
o Bronchospasm postoperative mucoid aspergillus skin
o Hyperinflation of alveoli (air trapping) impaction test; chest
o Atelectasis imaging; biopsy
o Consolidation and parenchymal fibrosis for BG
o Hemoptysis secondary to bronchial arterial erosion Congenital Anatomic Defects That May Cause Bronchial
Obstruction
i. TYPES Tracheobronchial Bronchomalacia; Chest CT
• Varicose Bronchiectasis (Fusiform Bronchiectasis) Abnormalities bronchial cyst; cartilage imaging
o The bronchi are dilated and constricted in an irregular deficiency (Williams-
fashion similar to varicose veins, ultimately resulting in Campbell syndrome);
a distorted, bulbous shape tracheobronchomegaly
• Cylindrical Bronchiectasis (Tubular Bronchiectasis) (Mounier-Kuhn
o The bronchi are dilated and rigid and have regular syndrome); ectopic
outlines similar to a tube. bronchus;
o X-ray examination shows that the dilated bronchi fail to tracheoesophageal
taper for 6 to 10 generations and then appear to end fistula
abruptly because of mucous obstruction. Vascular Pulmonary (intralobar) Chest CT
• – abnormalities sequestration; imaging
o The bronchi progressively increase in diameter until pulmonary artery
they end in large, cyst-like sacs in the lung parenchyma. aneurysm
o This form of bronchiectasis causes the greatest Lymphatic Yellow-nail syndrome History of
damage to the tracheobronchial tree. abnormalities dystrophic, slow
o The bronchial walls become composed of fibrous tissue growing nails
alone—cartilage, elastic tissue, and smooth muscle are Immunodeficiency States
all absent IgG deficiency Congenital (Bruton’s Quantitative
type) immunoglobulin
agammaglobulinemia; levels;
selective deficiency of immunoglobulin
subclasses (IgG2, subclass levels;
IgG4); impaired
acquired immune response to
globulin deficiency; immunization
common with
variable pneumococcal
hypogammaglobulinemi vaccine
a; Nezelof’s syndrome;
“bare lymphocyte”
syndrome
IgA deficiency Selective IgA deficiency Quantitative
± ataxia-telangiectasia immunoglobulin
syndrome levels
Leukocyte Chronic granulomatous Dihydrorhodamin
dysfunction disease (NADPH e 123 oxidation
oxidase dysfunction) test; nitroblue
tetrazolium
test; genetic
testing

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Other rare WHIM syndrome; Neutrophil count; iii. CLINICAL MANIFESTATIONS
humoral Hypergammaglobulinem quantitative • Decreased tactile and vocal fremitus
immunodeficienci ia M immunoglobulin • Hyperresonant percussion note
es levels
• Diminished breath sounds
(CXCR4 mutation,
• Wheezing
CD40
deficiency, CD40 • Crackles
ligand • Chronic cough with production of large quantities of foul-
deficiency, and smelling sputum
others)
Abnormal Secretion Clearance iv. DIAGNOSIS
Ciliary defects of Kartagener’s syndrome; Chest x-ray • Chest Radiograph - primarily obstructive in nature
airway ciliary dyskinesis showing situs 1. Translucent (dark) lung fields
mucosa (formally called impaired inversus; 2. Depressed or flattened diaphragms
ciliary motility bronchial biopsy; 3. Long and narrow heart (pulled down by
syndrome) ciliary motility diaphragms)
studies; electron 4. Enlarged heart (when heart failure is present)
microscopy of 5. Tram-tracks
sperm or 6. Areas of consolidation and/or atelectasis may or
respiratory may not be seen
mucosa • Bronchogram
Cystic fibrosis Typical early childhood Sweat chloride; o bronchography (the injection of an opaque contrast
(mucoviscidosis) syndrome; later genetic testing material into the tracheobronchial tree) was routinely
presentation with performed on patients with bronchiectasis.
predominantly
sinopulmonary
symptoms
Young’s Obstructive Sperm count
syndrome azoospermia with
sinopulmonary
Infections
Miscellaneous Disorders
Alpha1-antitrypsin Absent or abnormal Alpha1-
deficiency antitrypsin synthesis antitrypsin level
and unction
Recurrent Alcoholism; neurologic History; chest
aspiration disorders; lipoid imaging
pneumonia pneumonia
Rheumatic Associated with Rheumatoid
disease rheumatoid arthritis and factor;
Sjögren’s syndrome antiSSA/antiSSB
; salivary gland
MRI or biopsy
Inflammatory Crohn’s disease; History; lower
bowel disease ulcerative colitis gastrointestinal
endoscopy;
imaging studies;
colonic
biopsy
Inhalation of toxic Ammonia; nitrogen Exposure
fumes and dusts dioxide, or other irritant history; chest
gases; smoke; talc; imaging
silicates
Chronic organ Bone marrow, lung and History; PFT;
rejection following heart lung chest CT
transplantation transplantation; imaging with
associated with inspiratory and • Computed Tomography (CT Scan)
obliterative bronchiolitis expiratory views o The bronchial walls may appear as follows:
▪ Thick
▪ Dilated
▪ Characterized by ring lines or clusters
▪ Signet ring–shaped
▪ Flame-shaped

IV. CYSTIC FIBROSIS

• CF is a recessive gene disorder
• Characterized by bronchial gland hypertrophy and
metaplasia of goblet cells that leads to the excessive
production and accumulation of thick, tenacious mucus in the
tracheobronchial tree.
• The mucus is thick and inflexible, impairment of the normal
mucociliary clearing mechanism ensues, and many small
bronchi and bronchioles become partially or totally
obstructed (mucous plugging)
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 • Partial obstruction leads to overdistention of the alveoli, and
complete obstruction leads to patchy areas of atelectasis
and, in some cases, bronchiectasis
• Has both restrictive and obstructive lung characteristics, but
excessive bronchial secretions, bronchial obstruction, and
hyperinflation of the lungs are the predominant features of
CF in the advanced stages.
• Stagnant mucus in the tracheobronchial tree also serves as
an excellent culture medium for bacteria,
o Staphylococcus aureus
o Haemophilus influenzae
o Pseudomonas aeruginosa
• Major respiratory pathologic or structural changes
associated with CF are as follows:
o Excessive production and accumulation of thick,
tenacious mucus in the tracheobronchial tree
o Partial bronchial obstruction (mucous plugging)
o Hyperinflation of the alveoli
o Total bronchial obstruction (mucous plugging)
o Atelectasis
o Bronchiectasis
i. DIAGNOSIS & SCREENING
The following two criteria must be met to diagnose CF:
1. Clinical symptoms consistent with CF in at least one organ
system—for example:
a. pulmonary system,
b. sinus disease,
c. pancreatic disease,
d. meconium ileus,
e. biliary disease,
f. male infertility.
2. Clinical evidence of cystic fibrosis transmembrane
conductance regulator (CFTR) dysfunction—any of the
following:
a. Elevated sweat chloride >60 mEq/L (on two occasions)
b. Molecular diagnosis (Genetic Testing)>>Presence of
two disease-causing mutations in CFTR
c. Abnormal nasal potential difference
Newborn Screening
• Most infants with CF have an elevated blood level of
immunoreactive trypsin which can be measured by
radioimmunoassay or by an enzyme-linked immunoassay.
• The immunoreactive trypsin level (IRT) is measured from the
blood dots collected on all newborn infants on the Guthrie
cards.
• The diagnosis of CF is established by a positive sweat test
and/or genetic analysis for CF mutations.
• A negative or normal sweat test identifies the newborn as a
CF carrier.
Sweat Test (sweat chloride test)
• The gold standard diagnostic test for CF.
• This test measures the amount of sodium and chloride in the
patient’s sweat.
• During the procedure a small amount of a colorless, odorless
sweat-producing chemical called pilocarpine is applied to the
patient’s arm or leg.
• An electrode is attached to the chemically prepared area,
and a mild electric current is applied to stimulate sweat
production. The test is usually done twice.
• In both infants and adults, a sweat chloride concentration
greater than 60 mEq/L is considered to be a diagnostic sign
of CF
Molecular Diagnosis (Genetic Testing)
• With a sample of the patient’s blood or cheek cells, a genetic
test can be performed to analyze deoxyribonucleic acid
(DNA) for the presence of CFTR gene mutations.
• Intermediate results of sweat chloride testing should be
further investigated with a DNA analysis using a CFTR
multimutation method.
• It is estimated that genetic testing can confirm CF in about
90% to 96% of the patients tested
Nasal Potential Difference
• The impaired transport of sodium (Na+) and chloride (Cl−)
across the epithelial cells lining the airways of the patient
with CF can be measured.
• As the Na+ and Cl−ions move across the epithelial cell
membrane they generate what is called an electrical
potential difference—the amount of energy required to move
an electrical charge from one point to another.
• The NPD can be measured with a surface electrode over the
nasal epithelial cells lining the inferior turbinate.
• An increased NPD strongly suggests CF
Prenatal Testing
• fetus can be tested for CF by amniocentesis after the first
trimester.
• The amniotic fluid is obtained by ultrasound guided needle
aspiration of amniotic fluid from around the fetus.
• Fetal cells are tested for the presence of CF mutations and
identified as CF affected, CF carrier, or normal.
• Amniocentesis and genetic analysis of fetal cells can be
used to diagnose a large number of genetic disorders and
chromosomal abnormalities in the fetus
• Genetic counseling is very important in all cases of prenatal
testing for CF to explain this uncertainty or residual risk to
prospective parents. Amniocentesis and genetic analysis of
fetal cells can be used to diagnose a large number of genetic
disorders and chromosomal abnormalities in the fetus.
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Stool Fecal Fat Test
• The test measures the amount of fat in the infant’s stool and
the percentage of dietary fat that is not absorbed by the
body.
• Fat absorption requires bile from the gallbladder, enzymes
from the pancreas, and normal intestines. Under normal
conditions the fat malabsorption is less than 7 g of fat per 24
hours.
• An elevated stool fecal fat value (i.e., decreased fat
absorption) is associated with a variety of disorders,
including CF

ii. CLINICAL MANIFESTATIONS

Abnormal Laboratory Tests and Procedures
• Hematology
o Increased hematocrit and hemoglobin
o Increased white blood cell count
• Electrolytes
o Hypochloremia (chronic ventilatory failure)
o Increased serum bicarbonate (chronic ventilatory
failure)
• Sputum Examination
o Increased white blood cells
o Gram-positive bacteria
▪ Staphylococcus aureus
▪ Haemophilus influenzae
o Gram-negative bacteria
▪ Pseudomonas aeruginosa
▪ Stenotrophomonas maltophilia
▪ Burkholderia cepacia complex
• Chest Radiograph
o Translucent (dark) lung fields
o Depressed or flattened diaphragms
o Right ventricular enlargement (cor pulmonale)
o Areas of atelectasis and fibrosis
o Tram-tracks
o Bronchiectasis (often a secondary complication)
o Pneumothorax (spontaneous)
o Abscess formation (occasionally)
• Common Non-respiratory Clinical Manifestations
o Meconium ileus
▪ obstruction of the small intestine of the newborn
that is caused by the impaction of thick, dry,
tenacious meconium
▪ suspected in newborns who demonstrate
abdominal distention and fail to pass meconium
within 12 hours after birth.
▪ may occur in as many as 25% of infants with CF
o Meconium Ileus Equivalent
▪ an intestinal obstruction (similar to meconium ileus
in neonates) that occurs in older children and
young adults with CF
o Malnutrition and Poor Body Development
▪ pancreatic insufficiency that ensues inhibits the
digestion of protein and fat
▪ pancreatic insufficiency that ensues inhibits the
digestion of protein and fat
▪ leads to a deficiency of vitamins A, D, E, and K
▪ Vitamin K deficiency may be the cause of easy
bruising and bleeding
o Nasal Polyps and Sinusitis
▪ may cause nasal obstruction
▪ cause distortion of the normal facial features
o Infertility
▪ 99% of men with CF are sterile
▪ Women with CF who become pregnant may not be
able to carry the infant to term
▪ An infant who is carried to term will either have CF
or be a carrier
▪ Women with CF are sterile
▪ Women has risk for stillbirth