Chapter 13 Respiratory Disorders

Part II (of II)

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 Objectives cont.

❖Explain the pathophysiology of emphysema, the possible etiologies and signs and symptoms and treatments.

❖Explain the respiratory drive adaptation in patients with emphysema and the resulting possible risks associated with
oxygen administration.

❖Describe the pathophysiology of chronic bronchitis, the possible etiologies, signs & symptoms and treatments.

❖Describe the etiologies, pathophysiology and signs/symptoms of bronchiectasis.

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 Objectives, cont.

❖Explain the etiologies of pulmonary edema and its signs and symptoms.

❖List the risk factors, the etiologies, signs and symptoms for pulmonary embolism; understand the treatments.

❖Explain the etiologies of atelectasis.

❖Differentiate between the different types of pleural effusions and the etiologies of each type; know the signs
and symptoms.

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 Objectives, cont.

❖Explain the difference between open and closed and tension pneumothorax – what can cause each type.

❖Describe the etiologies of infant respiratory distress syndrome and its pathophysiology and signs and
symptoms.

❖Describe the etiologies of adult respiratory distress syndrome and its pathophysiology and signs and
symptoms.

❖List the more common types of lung carcinoma and describe the possible clinical manifestations seen with
lung carcinomas.

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Chronic Obstructive Pulmonary Disease

COPD = A group of chronic respiratory disorders characterized by progressive tissue degeneration and
obstruction of the airways.
◦ Emphysema and Chronic Bronchitis related to smoking are the most frequent causes.
◦ The absolute risk of COPD among active, continuous smokers is at least 25 percent.
◦ The disease is characterized by a progressive and incompletely reversible airflow obstruction.  

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 Emphysema

Etiologies:

◦ Cigarette smoking (most common cause)

◦ Cigarette smoke is the main cause of emphysema
◦ Increases number of neutrophils in lungs 🡪 neutrophils release many types of proteases 🡪 elastase
◦ Decreases activity of alpha-1 antitrypsin

◦ Air pollution
◦ Chronic inflammation 🡪 increases neutrophils & macrophages

◦ Secondary to other lung disorders

◦ Cystic fibrosis

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COPD: Emphysema

Emphysema is a disorder involving the destruction of

alveoli and parenchyma of lungs

End result is the development of large, permanently

inflated alveolar air spaces with lack of elastic recoil
◦ Emphysema initially involves the destruction of
tissue
◦ With repeated infections/chronic inflammation can
see scar tissue forming 🡪 fibrosis

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COPD: Emphysema - pathophysiology

Pathophysiology:
◦ Inflammatory cells secrete proteases (elastase) 🡪Breakdown of alveolar
wall and lung parenchyma
◦ Destruction of alveolar structures results in:
◦ Loss of surface area for gas exchange
◦ Loss of pulmonary capillaries – decreases perfusion
◦ Loss of elastic fibers – decreases lung recoil 🡪 air trapping
◦ Altered ventilation-perfusion ratio
◦ Decreased support for other structures – collapse of airways
Over time the chronic irritation/inflammation/infection results in fibrosis in
airways
◦ Narrowed airways
◦ Weakened walls
◦ Interference with passive expiratory airflow

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 COPD: Emphysema - pathophysiology
cont.

As disease progresses patients have increased difficulty with

expiration which results in:

• Air trapping and increased residual volume

• Over-inflation of the lungs
• Fixation of ribs in an inspiratory position
• Increased anterior-posterior diameter of thorax
• barrel chest
• Flattened diaphragm (on radiographs)

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 COPD: Emphysema pathophysiology cont.

Changes seen with advanced emphysema:

❖ Damaged alveoli coalesce forming large air spaces

◦ Known as emphysematous blebs or bullae

❖ Hypercapnia becomes the norm

◦ Chemoreceptors reset to elevated levels of carbon dioxide
◦ Respiratory acidosis is common

◦ remember the explanation for the occurrence of respiratory acidosis:

◦ CO2 + H2O H2CO3 H+ + HCO3-

❖ Frequent infections complicate the clinical course presenting as acute exacerbations

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 COPD - Chronic Bronchitis

Chronic Bronchitis is differentiated by significant

changes in the bronchi resulting from constant
irritation from smoking or industrial pollution

Inflammation of bronchi leads to obstruction of

bronchi
◦ Changes are cumulative and irreversible

Etiology
◦ Main cause is cigarette smoking
◦ Also associated with living in urban or industrial
areas
◦ Also associated with history of asthma

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COPD: Chronic Bronchitis

Pathophysiology:
• Due to constant irritation from cigarette smoke and pollution
• Mucosa becomes inflamed and swollen
• Hypertrophy and hyperplasia of mucus glands
◦ Increased secretions
• Fibrosis and thickening of bronchial wall
• Decrease in oxygen diffusion
◦ Severe dyspnea and fatigue
◦ Cyanosis
• Pulmonary hypertension – Cor Pulmonale can develop

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 COPD: Chronic Bronchitis

Clinical criteria for diagnosis of Chronic Bronchitis:

• Excessive production of tracheobronchial mucus
• At least two episodes of chronic cough each of 3 months duration or longer over a 2 year time period

Confirmation of diagnosis of Chronic Bronchitis:

• The diagnosis of COPD is confirmed using spirometry measurement to document airflow obstruction.
• COPD is confirmed by a post-bronchodilator FEV1/FVC ratio of less than 0.70. This differs from the finding in
asthmatic patients, whose airflow obstruction is fully reversible with bronchodilator therapy.

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COPD: Cor Pulmonale

Pulmonary hypertension and cor pulmonale

may develop in late stage COPD (emphysema
and /or chronic bronchitis)

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COPD clinical manifestations: Emphysema

Signs and symptoms of emphysema predominant COPD:

• “Pink Puffers”
• Dyspnea
◦ Initially with exertion
◦ Later develops at rest
• Hyperventilation/tachypnea
◦ prolonged expiratory phase
◦ Pursed lips to help with expiration
• Hyperinflation of lungs
◦ Air is trapped in lungs
◦ Development of “barrel chest”
• Anorexia and fatigue (weight loss)
• Secondary polycythemia

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 COPD: Chronic Bronchitis

Signs and symptoms of chronic bronchitis predominant COPD:

• “Blue Bloaters”
• Constant productive cough
◦ Copious, thick, purulent secretions
◦ Cough and rhonchi more severe in the morning
• Tachypnea and severe dyspnea
• Hypoxia, cyanosis, hypercapnia
◦ Due to airway obstruction
• Secondary polycythemia
• Signs of pulmonary hypertension and Cor Pulmonale
◦ Due to vascular damage and pulmonary hypertension
• Repeated respiratory infections occur

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Treatment Principles: COPD

Note: Patients with COPD will have clinical manifestations of BOTH Emphysema and Chronic Bronchitis.

Treatment:
◦ Avoid respiratory irritants (cigarettes, air pollution)
◦ Immunization against influenza and pneumonia
◦ Pulmonary rehabilitation
(Appropriate breathing techniques / respiratory hygiene / self management / appropriate exercise training)
◦ Maximize nutrition and hydration
◦ Bronchodilators
◦ Oxygen therapy may be indicated as condition advances
◦ Intermittent bouts of acute exacerbations due to bacterial bronchitis treated with antibiotics when indicated
◦ Occasionally will see lung reduction surgery or lung transplant in advanced disease

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 Bronchiectasis

Bronchiectasis refers to dilation of medium-sized bronchi which promotes pooling of secretions in airways
• See recurrent infections
• May affect one area of lung or affect entire lung

• Etiologies 🡪 usually develops secondary to another respiratory condition which promotes recurrent inflammation
and infection
• May be associated with COPD or CF or result from prior lung infections such as pneumonia

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Bronchiectasis, cont.

Pathophysiology:
◦ Changes primarily occur in the walls of medium-sized bronchi
◦ Chronic inflammation causes destruction of elastic tissue and weakening of muscle layer
◦ Results in dilation of wall
◦ Increase in mucus production due to inflammation
◦ Mucus will pool in dilated bronchi

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Bronchiectasis, cont.

Pathophysiology, cont.

◦ Pooled secretions are not cleared and become a culture medium for bacteria
◦ Usually see mixture of pathogens
◦ Bacterial infections further damage airways
◦ Increased destruction of cilia
◦ Lead to increased scarring and obstruction
◦ Metaplasia 🡪 change to squamous epithelium
◦ Loss of cilia which worsens the disease
◦ End result of dilation and excessive mucus is obstruction of airways

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Vascular Disorders

❑ Pulmonary Edema
❑ Pulmonary Embolism

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 Vascular Disorders – Cardiogenic Pulmonary
Edema

Pulmonary Edema refers to fluid collecting in alveoli and interstitial area

◦ Causes problems with gas exchange and lung expansion

Pathophysiology
◦ Under normal conditions pressure in pulmonary capillaries is low
◦ Various etiologies will cause fluid to shift from the vascular space to the alveoli and interstitial space

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Vascular Disorders – Pulmonary Edema, cont.

Pathophysiology, cont.
◦ Fluid in alveoli reduces amount of oxygen diffusing
into blood
◦ Fluid in alveoli and interstitial space interferes with
lung expansion
◦ Interferes with the action of surfactant 🡪 collapse
of alveoli

Etiology:
◦ Left sided heart failure is the most common cause
(cardiogenic pulmonary edema)

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Pulmonary Edema, cont.

Signs and symptoms:

◦ Cough, dyspnea, rales
◦ Orthopnea
◦ Paroxysmal nocturnal dyspnea
◦ Sensation of “drowning”
◦ Labored respirations
◦ Hypoxemia
◦ Cyanosis

Treatment:
◦ Treat causative factors (diuretics etc. for CHF)
◦ Supportive care
◦ Elevate upper body
◦ O2
◦ Possibility of positive-pressure mechanical ventilation

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 Vascular Disorders – Pulmonary Embolus

Pulmonary embolus = a blood clot or mass that obstructs pulmonary artery or a branch
thereof
Etiology:
◦ 90% of pulmonary emboli originate from deep vein thromboses in legs
◦ Other types of emboli
◦ Fat emboli (bone fractures)
◦ Vegetations from endocarditis

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Pulmonary Embolus cont.

Pathophysiology
◦ Effect of embolus depends on material, size, and
location
◦ Small pulmonary emboli might be “silent” unless
they involve a large area of lung
◦ “Shower of emboli” – multiple small emboli will
likely cause problems
◦ Emboli blocking medium-sized arteries:
◦ Obstruction of blood flow results in fluid and
blood filling up in alveoli
◦ Reflex vasoconstriction will also increase pressure
in blood vessels

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Pulmonary Embolus cont.

Larger emboli compromise Cardiovascular System –

example 🡪 “saddle embolus”
◦ “Saddle embolus” refers to an embolus that is
located at the bifurcation of the Pulmonary Trunk
(at the point where it divides into the Right and
Left Pulmonary arteries)
◦ A Saddle embolus significantly & suddenly
increases resistance to outflow from RV
◦ Acute right sided CHF i.e.
◦ Acute Cor Pulmonale
◦ Saddle embolus will also significantly decreases
cardiac output from the left side of the heart
because of the reduced return of blood from the
lungs
◦ Low BP (shock)
◦ Tachycardia /weak pulses
◦ LOC

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Pulmonary Embolus, cont.

Risk factors:
Anything that increases the risk of DVT also increases the risk of PE
◦ Immobility
◦ Trauma or surgery to legs
◦ Increased clotting tendency
◦ Pregnancy, OCP
◦ Smoking
◦ Malignancy

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Pulmonary Embolus cont.

Signs and symptoms:

◦ Small emboli
◦ Transient chest pain, cough
◦ Larger emboli
◦ Increased chest pain with coughing or deep breathing
◦ Sudden onset of tachypnea and dyspnea
◦ Hypoxia—causes anxiety, restlessness, pallor, tachycardia
◦ Later—hemoptysis and fever
◦ Massive emboli
◦ Severe crushing chest pain
◦ low blood pressure, rapid weak pulse
◦ loss of consciousness

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Pulmonary Embolus cont.

Treatment:
◦ Anticoagulants – Typically heparin or thrombolytics followed
by outpatient oral anticoagulation (months)
◦ +/- Mechanical ventilation
◦ +/- Embolectomy (saddle embolus)
◦ +/- Surgically inserted filter into vena cava for prevention of
further PE in come cases (e.g. if there is recurrence on
anticoagulation) - Greenfield Filter
◦ Assessment of risk factors & prevention of recurrence in
future

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 Expansion Disorders
❖ Atelectasis,
❖ Pleural Effusion,
❖ Pneumothorax,
❖ Infant Respiratory Distress Syndrome,
❖ Adult Respiratory Distress Syndrome (ARDS)

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Expansion Disorders – Atelectasis

Atelectasis refers to non-aeration or collapse of a lung or most commonly part of a lung

◦ Leads to decreased gas exchange and hypoxia

Pathophysiology
◦ Usually atelectasis occurs as a post-surgical complication or as a complication of another lung condition
◦ When ventilation of alveoli does not occur the gas in alveoli will be reabsorbed and the alveoli become airless and
collapse
◦ May then see inflammation, necrosis and atrophy of alveoli/lung tissue
◦ Process interferes with blood flow through the lung
◦ Blood will be shunted away from area of atelectasis – can worsen diffusion of gases
◦ End result is that both ventilation and perfusion are altered
◦ Affects oxygen diffusion

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 Resorption Atelectasis:
Atelectasis, cont.

Etiologies: Mechanisms that can result in atelectasis:

Postoperative atelectasis
• 24-72 hours after surgery
• Restricted ventilation due to pain and abdominal distention
• Respiratory depression due to anesthetic and analgesic drugs

Obstructive/resorption atelectasis
• Due to total obstruction of airway due to tumor, mucus etc.

Compression atelectasis
• Results when a mass (such as a pleural effusion) exerts
pressure on a part of the lung and prevents air entering that
area
 Atelectasis, cont.

Diagnosed by presence of clinical manifestations and x-ray findings:

◦ Small areas are asymptomatic
◦ Large areas
◦ Dyspnea
◦ Increased heart and respiratory rates
◦ Chest pain
◦ May see abnormal inflation (opacity) and / or shifting of structures on CXR

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Expansion Disorders – Pleural Effusion

Pleural effusion refers to the presence of excessive fluid in the pleural cavity
Pathophysiology
• Accumulation of fluid causes increased pressure in pleural cavity
– Results in decreased expansion of lung
– atelectasis
– If large may see:
– Shift of mediastinum toward unaffected lung
– Tracheal deviation on CXR

Effects vary depending on cause, rate of accumulation and type of exudate

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Categories of Pleural Effusions

Etiologies:
◦ Exudative effusions (relatively high protein content)
◦ Forms in response to inflammation
◦ Fluid has increased protein +/- WBC
◦ Response to inflammation from causes such as pneumonia or lung cancer

◦ Transudative effusions (relatively low protein content)

◦ Result of increased hydrostatic pressure or decreased osmotic pressure in blood vessels
◦ Seen with liver and kidney disease

◦ Hemothorax (bleeding in the pleural space)

◦ Blood
◦ Trauma or cancer

◦ Empyema (infection within the pleural space)

◦ Purulent pleural fluid
◦ May complicate infection such as pneumonia

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Pleural Effusion, cont.

Signs and symptoms

◦ Dyspnea
◦ Chest pain – pleurisy
◦ Friction rub
◦ Tachypnea
◦ Tachycardia
◦ Dullness to percussion and decreased breath
sounds
◦ Hypotension -> massive effusion

Treatment
◦ Remove underlying cause to treat respiratory
impairment
◦ Chest drainage, thoracentesis to remove fluid and
relieve pressure
◦ Analyze fluid to confirm cause

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 Pneumothorax

Pneumothorax refers to the presence of air in the pleural cavity:

Pneumothorax prevents full expansion of lung

Categories:
◦ Closed (aka spontaneous) – intact chest wall
◦ Tear on the surface of the lung including visceral pleura –
often seals leak as lung collapses (could be due to a “bleb”
on the surface of the lung
◦ Air can enter pleural cavity from internal airways – no
opening in chest wall
◦ Open – opening in chest wall
◦ Atmospheric air enters the pleural cavity though an opening
in the chest wall and parietal pleura
◦ May cause mediastinal “flutter” which would impair venous
return to the heart

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 Tension Pneumothorax

Tension pneumothorax:
◦ Most serious form
◦ Can be seen with open pneumothorax or closed
pneumothorax
◦ See one way valve effect from flap of tissue
◦ Air entry into pleural cavity on inspiration –
increases pressure on affected side
◦ Air is trapped on affected side with expiration
🡪increased pleural pressure and atelectasis
◦ See continued shift of mediastinum to
unaffected side and compression of unaffected
lung
◦ Also get compression of IVC

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Pneumothorax, cont.

Clinical manifestations:
◦ Dyspnea
◦ Cough
◦ Chest pain
◦ Decreased breath sounds over affected side
◦ Hypoxia
◦ Atelectasis
◦ Sympathetic NS response
◦ Anxiety, tachycardia, pallor
◦ Decreased venous return
◦ Hypotension

Treatment
◦ Correct underlying cause
◦ Chest tube

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 Expansion Disorders – Infant Respiratory
Distress Syndrome

IRDS, NRDS (neonatal respiratory distress

syndrome), Hyaline Membrane disease (HMD)

Etiology
◦ Usually related to premature birth with
reduced surfactant level

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Respiratory Distress Syndrome cont.

Pathophysiology
◦ Lack of surfactant in alveoli makes immature poorly developed alveoli difficult to inflate.
◦ Note: Surfactant is normally produced between 28 to 36 weeks gestation. (It reduces surface tension of
alveolar fluid)
◦ Diffuse atelectasis results.
◦ Decreased pulmonary blood flow – pulmonary vasoconstriction – severe hypoxia
◦ Lack of oxygenation results in acidosis – pulmonary vasoconstriction which decreases surfactant production
◦ Poor lung perfusion and lack of surfactant also cause
◦ Increased alveolar capillary permeability
◦ Fluid and protein are leaking into the interstitial area and alveoli – hyaline membrane formation

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Respiratory Distress Syndrome cont.

Signs and symptoms

◦ Respiratory difficulties may be evident at birth or shortly thereafter.
◦ Respirations rapid and shallow with chest retractions and flaring of nares

Diagnostic tests
◦ Arterial blood gas analysis
◦ CXR

Treatment
◦ Glucocorticoids to women in premature labor (to stimulate surfactant production)
◦ Synthetic surfactant to high-risk neonate
◦ Ventilation / Oxygen therapy

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Adult Acute Respiratory Distress Syndrome (ARDS)

Adult Respiratory Distress Syndrome (ARDS) is acute respiratory failure seen in critically ill patients with these
features:

Hypoxemia that persists even with 100% oxygen

Decreased pulmonary compliance
Dyspnea
Non-cardiac-associated pulmonary edema

ARDS can be caused by a wide variety of diseases, including :

◦ Pulmonary causes:
◦ Pneumonia
◦ Aspiration
◦ Non-pulmonary cause:
◦ Sepsis

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Acute Respiratory Distress Syndrome (ARDS)

Pathophysiology:

◦ Result from injury to the alveolar wall and capillary membrane

◦ release of inflammatory chemical mediators
◦ Increases permeability of alveolar capillary membranes
◦ Protein rich fluid leaks into interstitial area and alveoli 🡪 pulmonary edema
◦ Damage to surfactant-producing cells
◦ End result is decreased oxygenation, decreased pulmonary blood flow, difficulty expanding lungs and
atelectasis

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 Acute Respiratory Distress Syndrome (ARDS)

Signs and symptoms

– Dyspnea, rales, frothy sputum
– Tachypnea
– Combination of respiratory and metabolic acidosis
– Confusion, lethargy

Treatment
– Treatment of underlying cause
– Supportive respiratory therapy (mechanical ventilation usually necessary)
– Poor prognosis
– Mortality 30%-40%

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 Lung Cancer

Lung Cancer:
◦ Majority of lung cancers are primary
◦ However, the lungs are also common sites for secondary cancers
◦ due to lymphatic and venous return from distant sites reaching lungs
◦ Rarely see benign tumors of lungs – 3%

Primary Lung Cancer:

◦ One of the leading causes of cancer deaths in U.S.
◦ ~90% of cases due to smoking – all types of lung cancer
◦ Rare before age 40 years
◦ 5 year survival rate 10-15%
 Lung Cancer, cont.

Sequence of events leading to lung cancer:

◦ Chronic irritation and carcinogen exposure
◦ Cigarette smoke
◦ Pollution
◦ Initially leads to metaplasia of bronchial epithelium due to chronic irritation
◦ Changes to squamous epithelium
◦ Altered epithelium does not provide protection
◦ May be reversible – if remove irritant soon enough
◦ Eventually ongoing exposure to carcinogens lead to emergence of cancerous cells
◦ Metastases occur when cancer cells can breakthrough basement membrane and spread through lymphatics
and blood vessels
◦ Most common sites for metastases are brain, bone and liver
Lung Cancer, cont.

Etiology of Primary lung cancers:

◦ ~90% of cases due to smoking – all types of lung cancer
◦ Genetic factor
◦ Environmental exposures
◦ Second-hand smoke, radon, radiation, Asbestos

Primary lung cancer can arise from any type of tissue in lung
◦ Epithelial tissues lining the airways, Lymphatic tissue, Mesothelium and soft tissues

Most primary lung cancers arise from epithelial tissue in the bronchi and are known as Bronchogenic
Carcinomas
 Lung Cancer, cont.

Bronchogenic Carcinoma is a term that includes ALL lung cancers which arise from the bronchial
epithelium
◦ (Not just one type of lung cancer)

Bronchogenic carcinomas are divided into 2 major categories

◦ Categories are based on patterns of growth, spread and response to treatment
Two major categories of epithelial lung cancers:
◦ Non-small cell lung carcinoma (NSCLC) – this group accounts for approx. 85% of all lung cancer
◦ Squamous cell carcinoma
◦ Adenocarcinoma
◦ Large cell undifferentiated carcinoma
◦ Small cell lung carcinoma (SCLC) – 15 % (approx.)of all primary lung cancers
◦ Has strongest correlation with cigarette smoking
NSCLC – Adenocarcinoma

Adenocarcinomas
◦ ~40% of lung cancers (also the most common
NSCLC)
◦ Peripheral location
◦ Tumors arising from glandular epithelium
◦ Don’t see early signs/symptoms because of
peripheral location
◦ Usually associated with smoking but if a non-
smoker develops lung cancer, it is usually an
adenocarcinoma
NSCLC – Squamous Cell

Squamous cell carcinoma:

◦ Usually develops from epithelial lining of a
bronchus near hilum and projects into airway
◦ “Hilar location”
◦ Accounts for ~30% of lung cancers
◦ See early signs of obstruction
NSCLC – Large Cell Carcinomas

Large cell carcinomas

◦ Least common of the NSCLC lung cancers
◦ Peripheral location
◦ Metastasize early and have poor prognosis
SCLC (small cell lung carcinoma)

Small cell lung carcinoma:

◦ ~10 – 15 % of lung cancers
◦ Hilar location
◦ Often near major bronchus
◦ Very aggressive and invasive
◦ Worst prognosis
◦ Rarely occurs in non-smokers – has been
decreasing in incidence recently
 Signs and Symptoms of Lung Cancer

Signs and Symptoms are categorized based on:

◦ Direct effects of tumor on respiratory structures
◦ Systemic effects of cancer
◦ Paraneoplastic syndrome effects
◦ Metastatic tumor effects
Manifestations of Lung Cancer

Early signs – due to effects of tumor on respiratory structures:

◦ Insidious onset due to vague signs/symptoms which are often attributed to smoking or bronchitis
◦ Persistent productive cough from inflammation
◦ Hoarseness
◦ Frequent lower respiratory tract infections
 Manifestations of Lung Cancer, cont.

As tumor enlarges can see effects from compression or obstruction

on Respiratory Structures:
– Inflammation and bleeding surrounding the tumor
• Increasing cough, hemoptysis, secondary infections, pleural
effusions
– Obstruction of airflow – due to compression/obstruction of
bronchus by tumor or by enlarging lymph
• Abnormal breath sounds
• Dyspnea
• Atelectasis
– Superior Vena Cava Syndrome (seen here)
– Facial & arm edema
– See dilated neck veins
– Headache
– Hoarseness 🡪Compression of laryngeal nerve
– Dysphagia 🡪 Compression of esophagus
 General Manifestations of Lung Cancer, cont.

Paraneoplastic syndrome is seen with many forms of bronchogenic carcinoma:

◦ Tumor cells secrete hormones or hormone-like substances
◦ Signs and symptoms related to specific hormone secreted
◦ ADH (causes hyponatremia) – this is referred to as SIADH (syndrome of inappropriate ADH secretion)
(ADH = Antidiuretic Hormone)
◦ Parathyroid hormone (one cause of hypercalcemia)

Systemic signs
◦ Weight loss, anemia, fatigue
◦ May see DIC

Signs of metastases
◦ Bone pain, pathologic fracture, (another cause of hypercalcemia)
◦ Cognitive deficits, motor deficits – example seizure or headache due to metastases in brain
◦ Elevated liver function tests
 Lung Cancer Diagnosis and Staging

Diagnostic tests:
◦ Chest radiographs
◦ Sputum cytology
◦ Bronchoscopy with biopsy
◦ Specialized helical CT scans and MRI, bone scans
◦ Ultimately diagnosis will be confirmed by analysis of tissue biopsy
◦ PFT’s assess baseline respiratory function and contribute to assessing indicated therapies

Staging:
◦ With the use of the TNM cancer staging system, most solid tumors are staged on a scale of 1 to 4. In the TNM
system, T (T1-T4) refers to the size or extent of local invasion of the primary tumor, N (N0-N3) indicates
locoregional lymph node involvement, and M indicates the absence (M0) or presence (M1) of distant
metastases.
Lung Cancer: Treatment Principles

Treatment:
◦ Stop smoking
◦ Surgical resection or lobectomy
◦ Chemotherapy and radiation
◦ Targeted therapies - only work when the cancer cells have a particular target or specific genetic
mutation. (see prominent examples on next slide)
 Lung Cancer – targeted therapy

Important Molecular Alterations that can be targeted in treatment of NSCLC

Adenocarcinomas are tested for mutations prior to planning treatment:
◦ EGFR (Epidermal Growth Factor Receptor)
◦ Translocations involving ALK

Targeted Therapy:
◦ Erlotinib (Tarceva): a small molecule tyrosine kinase inhibitor targets cells with EGFR mutation)
◦ Crizotinib (Xalkori): also a small molecule tyrosine kinase inhibitor targets cells with ALK translocation)

Other targeted therapies for metastatic NSCLC:

Immunotherapy with agents that act on the programmed cell death ligand 1 (PDL-1) such as Pembrolizumab
(Keytruda) are used in metastatic NSCLC
 Early Diagnosis of Lung Cancer

Prevention of lung cancer by reduction in smoking is the MOST important intervention.

Early diagnosis is difficult – may be asymptomatic or minimal non-specific symptoms in early stages
Screening?
Routine chest x-ray screening is not effective BUT
USPSTF (United States Preventive Services Task Force) current recommendation: www.uspreventiveservicestaskforce.

The USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in:
❖ Adults aged 55 to 80 years who have
❖ A 30-pack-year smoking history and currently smoke or have quit within the past 15 years.
❖ Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that
substantially limits life expectancy or the ability or willingness to have curative lung surgery. 
IT’S NEVER TOO LATE TO STOP SMOKING.