Chapter 8 (pulmonary)

Question 1

acinus

Answer 1

Functional respiratory unit formed by the alveoli and the corresponding terminal bronchiole. 5-7 acini per pulmonary lobule. Each lobule is surrounded by connective tissue. Several lobules form a lobe.

Question 2

Describe the types of epithelium found as you descend the respiratory system from the nasal passages:

Answer 2

nasal pasages and paranasal sinuses: cuboidal epithelium (ciliated and mucous-producing cells)
Pharynx: Squamous epithelium (like mouth)
Larynx: Squamous epithelium (for phonation)
Trachea/bronchi/bronchioles/respiratory bronchioles: Cuboidal epithelium (ciliated cells, mucous-producing cells, neuroendocrine cells, and basal/progenator cells).

Question 3

Describe the basic pathogenesis of metaplasia arising from bronchial epithelium:

Answer 3

Chronic smoke exposure causes basal cells of cuboidal epithelium to proliferate and give rise to squamous cells. Most lung cancers originate this way, though histologically tumors can be composed of normal bronchial epithelial cells or those of metaplasia.

Question 4

Describe the respiratory defense system

Answer 4

Mucosa associated lymphoid tissue (MALT) form the tonsils in the nasopharynx and pharynx as well as lymphoid follicles in the walls of the bronchi.

Alveolar macrophages can also be expectorated into sputum.

Pulmonary capillaries serve as peripheral circulatory pool for leukocytes.

Question 5

List the 5 major categories of pulmonary disease:

Answer 5

1. Infectious
2. Immune
3. Environmentally induced
4. Circulatory diseases
5. Tumors

Question 6

Differentiate between Upper, lower, and “middle” respiratory diseases

Answer 6

Upper- Nose through larynx
Lower- lungs and bronchi
Middle- pediatric designation- refers to diseases of the larynx, trachea, and major extrapulmonary bronchi (includes croup, epiglottitis, bronchilitis- no alveolar involvement)

Question 7

What causes a “runny nose”?

Answer 7

Increased mucus production and corresponding ciliary action in nose and paranasal sinuses cause this drainage. This is a response to increased immunogenic activity to clear out pathogen laden macrophages etc.

Question 8

Croup

Answer 8

Acute laryngotracheobronchitis typically occuring in children <3yo. Causes barking cough. Etiology is typically parainfluenza.

Question 9

Epiglottitis

Answer 9

Clinically characterized by sudden loss of voice and hoarseness, throat pain, difficulty swallowing. H. influenzae is usual culprit.

Question 10

Bronchiolitis

Answer 10

acute infection involving bronchi and bronchioles but not extending into alveolar spaces. Pathophysiology involves invasion of cells of epithelium causing cell death and desquamanation, which combines with edema to obstruct small airways.

Typical etiology is RSV, but can also be caused by parainfluenza and rhinovirus. Cures spontaneously in 7-10 days unless joined by bacteria pneumonia.

Question 11

compare alveolar and interstitial pneumonia:

Answer 11

Alveolar pneumonia involves infiltrates that are primarily in the alveolar space. It can be local or diffuse and is often caused by bacteria.

Interstitial pneumonia involves infiltrates primarily located in the alveolar walls (no infiltrate into alveolar space). It is usually diffuse and often bilateral. Typically it is caused mycoplasma or viruses.

Question 12

bronchopneumonia

Answer 12

Alveolar pneumonia limited to the segmental bronchi and surrounding lung parenchyma.

Question 13

lobar pneumonia

Answer 13

Widespread or diffuse ALVEOLAR pneumonia.

Question 14

List important upper respiratory flora that can cause pneumonia?

Answer 14

S. pneumoniae (50%), H influenzae (10%), S aureus (5%).

Question 15

List 2 enteric saprophytes that can cause pneumonia:

Answer 15

E. coli; Psudomonas aeruginosa

Question 16

List some extraneous pathogens that can cause pneumonia:

Answer 16

Legionella pneumophila, Mycobacterium tuberculosis (5%), fungi, viruses (10%), Mycoplasma pneumoniae (10%)

Question 17

hypostatic pneumonia

Answer 17

Pneumonia infection preceded by fluid filled alveoli from pulmonary edema of CHF.

Question 18

List some complications of bacterial pneumonia (3): viral?

Answer 18

1. Pleuritis- Extension of inflammation to pleural surface. Commonly leads to pleural effusion. If pus fill pleural cavity it is called pyothorax, if it is encapsulated into fibrous tissue pockets it is empyema. In healing this will cause pleural fibrosis, obliterating the pleura and causing restrictive lung disease.
2. Abcess- associated with virulent bacteria like Staphylococcus. Causes destruction of lung parenchyma.
3. Chronic lung disease- This can include bronchiectasis (pus in bronchi destroys walls and causes bronchial dilation), destruction of lung parenchyma (interstitial fibrosis) and cysts.

The main complication of viral peumonia is bacterial superinfection. Occasionally unresolved viral pneumonia can cause fibrosis.

Question 19

What is the difference between primary and secondary pneumonia?

Answer 19

Primary or “community acquired” pneumonia affects healthy people. Secondary pneumonias are either nosocomial or occur in persons with preexisting illness.

Question 20

How is pneumonia diagnosed?

Answer 20

Clinical suspicion (dyspnea, cough, fever, rales, consolidation signs) PLUS CXR, sputum culture, or peripheral blood study showing leukocytosis (bacterial) or lymphocytosis (viral).

Question 21

What is atypical pneumonia and how does it present clinically and pathophysiologically?

Answer 21

Milder symptoms (low fever, no chills, dry cough). Xray findings are minimal with no distinct condensations. Bacteria cannot be cultured from sputum. No septicemia, no purulent pleuritis or abcess formation.

Diagnosis is made through serology to known pathogens (eg Mycoplasma).

Question 22

What is primary TB? Ghon complex?

Answer 22

On initial infection there is localized inflammation in the lung. Eventually this will cause granulomas (epithelioid macrophages, giant multinucleated cells, caseous necrosis, no PMNs). Granulomas of primary TB and enlarged regional lymph nodes form Ghon complex. Eventually the complex will calcify, but there may be M. tuberculosis living in the calcified lesion.

Primary TB rarely progresses except in children and immunosuppressed.

Symptoms are usually mild (95% of cases are unrecognized) with low grade fever and cough.

Question 23

How does secondary TB occur? What does it look like clinically?

Answer 23

It is usually reactivation of a dormant primary infection (though it can be a reinfection). The bacteria spread to the apices of the lung where they form granulomatous lobular pneumonia. Confluent granulomas can form cavities (cavernous TB).

Symptoms of secondary TB are low fever, nonproductive cough, loss of appetite, malaise, night sweats, and weight loss. Hemoptysis occurs late.

Secondary TB can progress into miliary TB, tuberculous pneumonia, pleuritis, or extrapulmonary TB.

Question 24

What does fungal lung disease look like? What are some possible etiologies? For immunocompromised people?

Answer 24

It looks like primary TB, and usually causes formation of solitary granulomas. Histoplasmosis is widespread in the midwest. Cocciciodomycosis is endemic in Southwestern deserts.

For immunocompromised: P. jiroveci, Candida albicans, Aspergillus fumigatus.

Question 25

Which pathogens cause pulmonary abcesses? How?

Answer 25

S. aureus is most common. Others are Klebsiella pneumoniae and P. aeruginosa. Staph does this as part of its normal disease history. Others occur after aspiration of infected material from the upper respiratory tract, distal to bronchial obstruction by tumors, or as a result of septic emboli.

Question 26

Compare COPD caused by chronic bronchitis and emphysema:

Answer 26

Chronic bronchitis: cough and expectoration for min 3 months during 2 consecutive years. Walls of bronchi and bronchioli are thickened and their lumen contains thick mucous. Histologically, surface epithelium is preserved (may show metastatic changes), but submucosa shows marked mucous gland hyperplasia, chronic inflammation, and fibrosis. Often leads to bronchiectasis. (“Blue bloaters”)

Emphysema is enlargement of the airspaces distal to the terminal bronchioles with destruction of the alveolar walls. (“pink puffers”). Repeat injury causes chronic inflammation in the alveoli. Degrading enzymes, including leukocyte derived elastase, destroy alveolar walls and their elastic fibers. The result is increased lung compliance and loss of elasticity.

Question 27

Bronchiectasis

Answer 27

a permanent dilation of the bronchi. It is the most common complication of chronic bronchitis but also occurs in CF. Larger bronchi show saccular or cystic dilation, while smaller bronchi and bronchioli show cylindrical dilation. In both the dilated bronchi are filled with mucopurulent material that cannot be cleared by coughing.

Complications are low fever, malaise, fatigue, clubbing, and secondary amyloidosis.

Question 28

Differentiate between centrilobular and panacinar emphysema:

Answer 28

Centrilobular is marked by widening of airspace at center of a lobule and involves predominantly the respiratory bronchioles. It is the more common form, and is caused by smoking.

Panacinar involves all airways distal to terminal bronhioles (including respiratory bronchioles and alveoli). This type occurs in alpha1-AT deficiency, but also smoking.

Question 29

What is a blue bloater?

Answer 29

Pt with COPD predominated by chronic bronchitis. Characterized by coughing, expectoration of tenacious or purulent mucus, and dyspnea. Hypoxia can be pronounced, causing central cyanosis. Pulmonary vasculature is affected by peribronchial fibrosis resulting in pulmonary hypertension and chronic cor pulmonale.

CXR shows increased bronchiovascular markings and an enlarged heart.

Question 30

What is a “pink puffer”?

Answer 30

Pt with COPD predominated by emphysema. NO COUGH. Sx are dyspnea, DOE, compensatory tachypnea, barrel-chest, tripoding, pursed lip breathing, engagement of auxilary muscles. CXR shows overinflation. These pts are rarely cyanotic.

Question 31

What are the 4 most important immune diseases of the respiratory system?

Answer 31

1. Allergic rhinitis
2. bronchial asthma
3. sarcoidosis
4. hypersensitivity pneumonitis

Question 32

Compare extrinsic and intrinsic asthma:

Answer 32

Extrinsic asthma is the more common type among children and is mediated by exposure to endogenous allergens (type I hypersensitivity). Often this affects pts with other allergies. Typically diagnosed in children under 10, 50% of cases resolve.

Intrinsic asthma is precipitated by non-immune mechanisms (exercise, cold, stress, irritants, infection, aspirin) that would not normally cause problems in the bronchii, except that they are already in a heightened state of inflammation. Typically this begins in adulthood <40 yo

Question 33

Sarcoidosis

Answer 33

Etiology is poorly understood. Affects blacks more than others, and women more than men. The lungs (or lymph nodes, or liver) are infiltrated with CD4-T lymphs (10:1 cd8) where they contribute to the formation of noncaseating granulomas. ACE may be elevated. 70% of patients spontaneously cure. 20% have persistent disease. 10% die.

Question 34

List some important antigens in hypersensitivity pneumonitis:

Answer 34

Most are derived from molds and fungi growing on organic material, or contaminated fluid. There are also several specific to certain hobbies/occupations:
Farmer's lung (mold on hay or grain)
Bagassosis (sugar cane)
Mushroom worker's lung
Humidifier lung
Pigeon-breeder-s lung

Question 35

Distinguish between acute and chronic hypersensitivity pneumonitis:

Answer 35

Acute: Mediated by antibodies that react with inhaled antigen in the alveoli, which turns on the complement cascade for an influx of leukocytes. Evolves over several hours and causes alveolar injury. Presents as acute dyspnea and can be managed by having pt avoid the original antigen.

Chronic: Mediated by T lymphocytes and characterized by a typical cell-mediated reaction. Granulomas form in the alveolar septa causing their thickening and destruction. Eventually these will become “honeycomb lungs”. Hard to identify antigen. Only tx is lung transplant.

Question 36

what is pneumoconiosis?

Answer 36

lung diseases caused by inhalation of mineral dusts, fumes, and various organic or inorganic particulate matter. Result is restrictive lung disease.

Question 37

How does inhalation of mineral particles damage the lungs?

Answer 37

The exact mechanism is not known, but the extent of the injury depends on the duration of exposure, concentration of particles, particle size (smaller is worse), shape, and solubility, and the biochemical composition of inhaled dust.
Silica is highly reactive and produce prominent tissue injury whereas coal dust is more inert (though it contains silica). Asbestos particles are insoluble and tend to lodge in the alveoli.
Pathogenesis is mediated by macrophages ingesting particles and then causing a pro-inflammatory cascade ultimately resulting in fibrosis, remodeling, and loss of resp. surface area.

Question 38

Pathogenesis of coal-workers lung disease

Answer 38

Blackening of lungs, while it may look bad, is due to accumulation of carbon in pulmonary interstitial spaces, around bronchi, and underneath the pleura. It’s actually harmless.

Coal workers lung-disease occurs over long-term exposure to dust that is rich in carbon AND other minerals (like silica). These particles are deposited in the centrolobular zones of the lung and may cause fibrosis or centroacinar emphysema. CWLD will not occur in safe mining conditions with good ventilation. Does NOT predispose pt to lung cancer.

Question 39

How does silicosis present pathologically?

Answer 39

Silicosis is the most common lung disease caused by mineral particles (silica is the most ubiquitous substance in the earth’s crust). It takes 20-30 years of exposure to mining, sand blasting, or stone cutting.

Silica particles 1-3um in size are taken up by macrophages, which are damaged or killed. The silica crystals are released along with biologically active substances that stimulate fibroblasts to produce collagen. Collagenous nodules are formed, which are most prominant along the lymphatics draining toward the hilar lymph nodes. Also predisposes to TB infection.

Pts. are usually asymptomatic until substantial lesions develop. Lesions are irreversible, but do not predispose pt to cancer.

Question 40

Which (4) lung diseases are related to exposure to asbestos?

Answer 40

1. Pulmonary fibrosis
2. Pleural fibrosis and pleural plaques
3. Lung cancer
4. Mesothelioma

Question 41

How do patients with asbestosis present clinically?

Answer 41

Pts. have restrictive lung disease and dyspnea. They will either have pulmonary fibrosis, with pleural fibrosis and plauques, lung cancer, mesothelioma, or a combination.

Question 42

What are “asbestos bodies”?

Answer 42

On histologic examination, these are fibrous tissue (formed by macrophages that have induced fibroblasts to remodel after taking up asbestos [but not dying like in silicosis]). Fibrous tissue contain beaded bodies with knobbed ends, coated with hemosideren pigment, making them appear brown. Also called “ferruginous bodies”

Question 43

compare the pathologic findings in wet drowning vs. dry drowning:

Answer 43

Wet drowning occurs when aspirated water enters the respiratory tract, fills the airways, and prevents the entry of air. This is the more common type.

Dry drowning occurs as a result of reflex laryngospasm and closure of the glottis, which prevents air and water from entering. These patients are more easily resuscitated.

Question 44

What are the 4 main pathogenic mechanisms of ventilatory failure?

Answer 44

1. Neural control of respiration- damage to respiratory center
2. Respiratory muscles- diaphragm, intercostals can be impaired by spinal cord or cranial nerve lesions, peripheral nerve lesions, or pathology and neuromuscular junction. Eg. poliomyelitis, myasthenia gravis
3. Chest wall- Lesions that restrict expansion of chest wall: deformity, pleural fibrosis, pleural tumors, extreme obesity (Pitwickian syndrome)
4. Airways- laryngospasm (croup), bronchial mucous plugs (CF), alveolar lesions like interstitial pulmonary fibrosis.

Question 45

Describe the pathophysiology of ARDS:

Answer 45

See figure 8-21 and 8-22 on pg 185. Basically ARDS can originate from damage to the capillary endothelium or the alveolar epithelium. The capillary mechanism is an inflammatory pathway leading to increased tissue permeability of the alveolar septa and edema, hemhorrage, hyaline membrane formation, straining the heart and causing death by cardiopulmonary failure. This occurs in sepsis or with cytotoxic drugs.

In the alveolar mechanism causes direct damage to alveoli (type I and II pneumocytes) causing rupture and decreased surfactant production, atelectasis, and ARDS. This pathway is occurs in pneumonia or after inhaling toxic fumes.

Irrespective of the mechanism, the lungs show diffuse alveolar damage. Histologically, the alveolar spaces are dilated and filled with proteinaceous edema, with hyaline membrane formation in the septa.

Question 46

Describe the outcomes of ARDS:

Answer 46

1/3 die within days; 1/3 die of pneumonia and heart failure within weeks; 1/3 recover. Of those who recover 40% have permanent residual respiratory problems as a consequence of fibrosis.

Question 47

What is atelectasis and how does it occur?

Answer 47

Incomplete expansion or collapse of alveoli. It occurs through 3 mechanisms:

1. Surfactant deficiency (premature neonates)
2. Compression due to fluid, tumors (causing effusion), or pneumothorax
3. Resorption: When a single bronchus is obstructed by a foreign body, tumor etc, the air in the alveoli distal to the blockage is resorbed and the alveolar walls collapse.

Question 48

What are the most common neoplasms of the respiratory tract?

Answer 48

Lung cancer and carcinoma of the larynx

Question 49

Describe the pathology and clinical findings in carcinoma of the larynx:

Answer 49

Pts present early in disease course with sx of hoarseness, loss of voice or stridor. Pathology is related to smoking and chronic alcohol consumption. Tumors can be supraglottic or infraglottic.

Disease tends to occur in adults over 40 with males:females 7:1

Question 50

How common is lung cancer?

Answer 50

It is the most common malignant disease of internal organs and the leading cause of cancer death in the US.

Question 51

How is tobacco smoking related to lung carcinoma?

Answer 51

Overwhelming epidemiolgic evidence. Direct pathogenic process is not entirely understood, however it contains several known carcinogens. The proposed process is:

1. Inhaled procarcinogens are converted into carcinogens through action of cytoplasmic enzymes in bronchial cells.
2. Chronic irritation causes transformation of cuboidal epithelium (reversible lesion) to squamous metaplasia
3. With persistant exposure the basement membrane is compromised and oncongenic transformation occurs (either activation of oncogene or deactivation of tumor suppressor).

Question 52

Adenocarcinoma

Answer 52

40% of all Lung carcinoma and the only one that occurs in non-smokers (5:1 smokers to non). Involves transformation of ciliated and mucous cells of epithelium that will be characterized on pathology by intracytoplasmic vacuoles containing mucin.

NSCLC

Always rule out metastasis of colonic adenocarcinoma.

Tx is surgery with adjuvant radiation and chemo.

Question 53

Small-cell carcinoma

Answer 53

15% of all lung carcinomas (100:1 smokers:non). Involves transformation of neuroendocrine cells in bronchi and bronchioles. Highly malignant and rapidly progressing.

Tx is chemo only. Prognosis is very poor.

Question 54

Squamous cell carcinoma

Answer 54

30% of all lung carcinomas. Caused by transformation of normal cuboidal epithelium to squamous cells. Lesion is of squamous cells.

A common lab finding is elevated serum calcium. Be sure to r/o metastasis from a bone lesion if this is the case.

NSCLC

Tx is surgery with adjuvant radiation and chemo.

Question 55

Large-cell undifferentiated carcinoma

Answer 55

10% of lung carcinomas. Caused by transformation of stem cells of cuboidal epithelium. Lesion is of undifferentiated cells.

NSCLC

Tx is surgery with adjuvant radiation and chemo.

Question 56

Carcinoid

Answer 56

A neuroendocrine tumor (like small-cell) of low-grade malignancy Tend to invade locally and grow slowly and do not metastasize to distant places.

Tx is surgical resection.

Question 57

Compare hilar to peripheral lung carcinoma:

Answer 57

Part of macroscopic pathologic classification. Hilar tumors are attached to the bronchi and extend into adjacent parenchyma or bronchial lumen.

Peripheral can form subpleural nodules or present as a consolidationor present as a consolidation of pulmonary parenchyma. May originate from small bronchi, bronchioles, or type II pneumocytes trapped in fibrous tissue.

Question 58

Where do lung cancers metastasize?

Answer 58

Local (hilar and mediastinal) lymph nodes, liver, brain, bones, kidneys, adrenals.

Question 59

What are the common paraneoplastic syndromes caused by lung carcinoma?

Answer 59

1. Hypercalcemia from parathyroid-like polypeptide
2. Cushing’s syndrome due to overstimulation of adrenals by adrenocorticotropic hormone (ACTH)
3. Volume overload and dilutional hyponatremia due to ADH

Question 60

Mesothelioma

Answer 60

a malignant tumor of the pleura related to asbestos exposure. Invasive locally but do not metastasize outside the thorax until late in disease course. Prognosis is poor.