Lecture 6.1

Question 1

Describe the normal development of the lungs

Answer 1

1) During embryogenesis, the respiratory system grows out from the ventral wall of the foregut
2) Midline trachea develops into lung buds
3) R lung bud divides into three main bronchi and the L into two > hence 3 Right lobes and 2 Left
4) Main bronchi continue to bifurcate into smaller and smaller airways, eventually dubbed “bronchioles” which have lost their cartilage and submucosal glands
5) These lead to “terminal bronchioles”
-The most distal part of these is called an “acinus” and these are composed of alveolar ducts and sacs
6) Of course, it is in the capillaries surrounding alveoli that respiratory gasses are exchanged

Question 2

Atelectasis:
1) Define it
2) What does it result in?
3) What is the basic principle?

Answer 2

1) Also known as “collapse,” this should not be confused with pneumothorax
2) Loss of lung volume caused by inadequate expansion of airspaces
3) “Use it or loose it”
-After the precipitating factor of atelectasis, physiologic “shunting” of blood occurs
-Blood moves from poorly perfused areas with inadequate gas exchange to elsewhere
-The alveoli, in turn, begin to close

Question 3

Define ARDS

Answer 3

“Respiratory failure occurring within 1 week of known clinical insult with bilateral opacities on chest imaging that is not fully explained by effusions, atelectasis, cardiac failure, fluid overload”

Question 4

ARDS:
1) How can it occur?
2) What is it associated with?
3) What are the MC triggers?

Answer 4

1) In several different clinical settings
2) Primary pulmonary diseases and severe systemic inflammatory disorders: aka sepsis
3) PNA 35%-45%; Sepsis 30%-35%; Aspiration, trauma, pancreatitis, transfusion reactions

Question 5

Differentiate between restrictive and obstructive Dz

Answer 5

1) Obstructive: characterized by increase in resistance to air flow – measured by difficulty blowing out
2) Restrictive: characterized by reduced expansion of lung and decreased total lung capacity

Question 6

The four main types of obstructive disease are what? Describe each briefly

Answer 6

1) Emphysema: alveolar wall destruction, overinflation
2) Chronic bronchitis: productive cough, airway inflammation
3) Asthma: reversible obstruction; bronchial hyperresponsiveness with a trigger
4) Bronchiectasis: involves scarring of the airways

Question 7

Emphysema:
1) Define it
2) What are the 2 types?

Answer 7

1) Permanent enlargement of air spaces distal to terminal bronchioles (the acinus) with permanent destruction of their walls and significant fibrosis
2) Centriacinar and panacinar

Question 8

Emphysema:
1) Which is the one smokers get? What is affected in this type?
2) Describe the second type of emphysema. When does it occur?

Answer 8

1) In centriacinar emphysema the central or proximal parts of acini are affected, and distal alveoli are spared
-This is the one smokers get
2) In panacinar emphysema the acini are uniformly enlarged
This occurs with alpha-1 antitrypsin deficiency

Question 9

How do you get emphysema from alpha-1 antitrypsin?

Answer 9

1) Genetic disease affecting the lungs and liver
2) In the lung, alpha-1 antitrypsin is underproduced
- it is therefore unable to inhibit elastase
- elastase breaks down elastin in the lung
- acinus is affected as in normal emphysema – (but panacinar)
- obstructive disease
* homozygous disease more severe

Question 10

What does Alpha-1 antitrypsin do?

Answer 10

Usually present in serum, tissue fluids, macrophages: it inhibits elastase, which breaks down elastin

Question 11

Emphysema:
1) What is the primary Sx?
2) What compensates it? What does this lead to?
3) What do you see on PE?

Answer 11

1) Dyspnea
2) Hyperventilation, which leads to increased energy demands and weight loss that is often profound
-Caloric intake is also sometimes reduced
3) Tachypnea, pursed-lip breathing, hunched posture, barrel chest

Question 12

What are the 3 secondary effects of emphysema? Describe each

Answer 12

1) Pulmonary hypertension: Physiologic Shunting
2) Obstructive overinflation: Expansion of the lung due to air trapping
3) Bullae: Large, empty spaces in the lung where tissue is completely lost

Question 13

Chronic Bronchitis:
1) In early stages, cough raises mucoid sputum, but airflow is not yet obstructed; what does this look like?
2) From there, the course is variable, but late-stage findings include what?

Answer 13

1) pts may have hyperreactive airways, though, that lead to intermittent bronchospasm and wheezing
2) Significant outflow obstruction: Hypercapnia, hypoxemia, cyanosis
-Pulmonary hypertension > you know where this leads. . .
COPD pts. with bronchitis often have more rapid disease progression with poorer outcomes than the isolated emphysema type

Question 14

Define asthma

Answer 14

“Chronic inflammatory disorder marked by intermittent, reversible airway obstruction, chronic bronchial inflammation with eosinophils, bronchial smooth muscle hypertrophy and hyperreactivity”

Question 15

What are the 2 types of asthma?

Answer 15

Atopic – hypersensitivity type I
Non atopic

Question 16

Non-atopic asthma:
1) What would allergen skin test results be?
2) What may trigger attacks?
3) How does the Tx differ from atopic?

Answer 16

1) Do not have evidence of allergen sensitization and thus allergen skin tests for offending agent are usually negative
2) Attacks may still be triggered by viral illness and air pollutants
3) Many of the inflammatory mediators are the same and the treatment does not vary from atopic
Less often any family history

Question 17

These patients have recurrent episodes of wheezing, breathlessness, chest tightness and cough particularly when?

Answer 17

At night

Question 18

1) What are some triggers of asthma attacks?
2) What abt specifically in the atopic type?

Answer 18

1) Most commonly viral illness, but often smoke, fumes, cold air, stress, exercise
2) Triggers may also include pollen, dust, animal dander, food
Onset of asthma attack may be preceded by rhinitis, urticaria, eczema

Question 19

Asthma Tx involves direct response to the processes discussed. Explain what the 3 main options are.

Answer 19

1) Bronchodilators > beta-adrenergic drugs
2) Anti-inflammatory > steroids
3) Leukotriene inhibitors

Question 20

Bronchiectasis:
1) Describe the cough and sputum
2) When do the Sx occur?

Answer 20

1) Severe persistent cough
Expectoration of copious sputum
Sometimes fetid and mucopurulent
2) Intermittent sx, correlate with new infections

Question 21

Describe a typical Idiopathic Pulmonary Fibrosis Patient and what their CT scan would look like

Answer 21

1) Older
2) Male
3) Chronic, nonproductive cough
4) “Dry” crackles on inspiration
5) Late stage cor pulmonale
6) “Honeycombing” on CT

Question 22

List and describe 2 rare fibrosing diseases

Answer 22

1) Nonspecific interstitial pneumonia: Less severe than IPF
2) Cryptogenic organizing PNA: Severe disease that sometimes resolves spontaneously

Question 23

Pneumoconiosis General Pathology:
1) What particulate is trapped? Where?
2) What accumulates? What does this initiate? Describe the response

Answer 23

1) 1-5 micrometer particulate is trapped in distal lung in alveolar duct bifurcations
2) Macrophages accumulate and engulf trapped particles
-Inflammatory response initiated  fibroblasts proliferate
-cells drain to lymphatics and amplify immune response through adaptive system

Question 24

Coal Worker’s Pneumoconiosis (Anthracosis):
1) What does illness depend on? Why?
2) What is occurring in the body?

Answer 24

1) The extent of damage; coal is inert and so can rest in the lung a long time, building up large amounts before having an effect
2) Macrophages engulf carbon pigment and accumulate in connective tissue along pulmonary and pleural lymphatics

Question 25

Coal Worker’s Pneumoconiosis (Anthracosis): differentiate between the simple and complicated types

Answer 25

1) Simple: Marked by “coal macules” and “coal nodules” -Once lower lobes are heavily involved these pts develop emphysema -Fibrotic element can progress to “progressive massive fibrosis” or “complicated CWP” 2) Complicated: Simple CWP + multiple, dark black scars, between 2-10 cm in length -Continues to worsen even after no more exposure -Pulmonary HTN; cor pulmonale

Question 26

1) Most prevalent chronic occupational disease in the world is what? Why? 2) What is occurring in the body w this disease?

Answer 26

1) Silocosis; Sandblasting and hard-rock mining -Quartz, crisobalite, tridymite 2) Deposition in epithelial cells  fibrosis  “PMF” (progresisive massive fibrosis)  pulmonary HTN, cor pulmonale

Question 27

Asbestosis: 1) What causes it? 2) What condition does it lead to? 3) What is a key feature from occupational medicine?

Answer 27

1) Fibers deposited in lung  eaten by macrophages  inflammation/ fibrosis  “diffuse pulmonary interstitial fibrosis with ‘asbestos bodies’” 2) Mesothelioma 3) Families of workers are also exposed

Question 28

Asbestosis: Pt’s develop worsening dyspnea 10-20 years after exposure, describe why

Answer 28

1) Parenchymal interstitial fibrosis 2) Localized fibrous plaques 3) Pleural effusions 4) Lung carcinoma 5) Malignant pleural and peritoneal mesothelioma 6) Laryngeal carcinoma *Risk of cancer goes way up if they are also smoking

Question 29

Hypersensitivity Pneumonitis: 1) What mediates it and what does it primarily effect? 2) What is it usually caused by?

Answer 29

1) Immunologically mediated lung disease that primarily affects the alveoli (allergic alveolitis) 2) Occupational exposure and heightened sensitivity to inhaled antigens -pigeons, hot tubs, random things, etc

Question 30

Pulmonary embolus: 1) Almost all large pulmonary artery thrombi are what in origin? From where? 2) What are risk factors?

Answer 30

1) Embolic in origin, usually arising from the deep veins of the lower leg 2) Prolonged bed rest, knee or hip surgery, severe trauma, use of oral contraceptives (especially those with high estrogen content), disseminated cancer, and genetic causes of hypercoagulability.

Question 31

Pulmonary embolus: 1) What do most emboli cause? Explain 2) Is there a risk for recurrence?

Answer 31

1) Most emboli (60% to 80%) are clinically silent; a minority (5%, typically large “saddle emboli”) cause acute right-sided heart failure, shock, or sudden death; and the remainder cause pulmonary infarction. 2) Risk for recurrence is high

Question 32

Pulmonary HTN: 1) Define and describe it 2) What are the initial Sx? 3) What are the chronic Sx?

Answer 32

1) **Pressures of 25 mm Hg or more at rest**; decrease in the cross-sectional area of the pulmonary vascular bed or, less commonly, by increased pulmonary vascular blood flow. 2) Dyspnea and fatigue 3) Respiratory distress, cyanosis, and RVH

Question 33

WHO classification of HTN: What is the definition? What are the 4 groups of causes?

Answer 33

Affecting small pulmonary muscular arterioles; i.e. connective tissue diseases, HIV, and congenital heart disease (left to right shunts) 1) Pulmonary hypertension due to **left-sided heart disease**, including systolic and diastolic dysfunction and valvular disease 2) Pulmonary hypertension due to **lung diseases and/or hypoxia**, including COPD, interstitial lung disease, and sleep apnea 3) **Chronic thromboembolic pulmonary hypertension** 4) Pulmonary hypertension with **unclear or multifactorial mechanisms**

Question 34

1) Define pneumonia 2) How many deaths in the US?

Answer 34

1) Any infection in the lung 2) One-sixth of all deaths in the U.S.

Question 35

List the 7 types of pneumonia

Answer 35

1) Community Acquired Bacterial Pneumonia 2) Community Acquired Viral Pneumonia 3) Nosocomial Pneumonia (hospital acquired) 4) Aspiration Pneumonia 5) Chronic Pneumonia 6) Necrotizing Pneumonia & Lung Abscess 7) Pneumonia of the Immunocompromised patient

Question 36

Acute Pneumonias: 1) What is the most common cause? 2) What do they involve? 3) List some characteristics

Answer 36

1) S. pneumoniae (the pneumococcus) is the most common cause of community-acquired bacterial pneumonia and usually has a lobar pattern of involvement. 2) Morphologically, lobar pneumonias involve an entire lobe and are bound by fissure lines. 3) Congestion: Lung is heavy, boggy, and red. Red Hepatization: Massive confluent exudation as neutrophils, red cells and fibrin fill the alveolar spaces Resolution: exudate broken down by enzymatic activity

Question 37

What are the clinical features of acute pneumonias?

Answer 37

1) Onset is usually abrupt 2) Often follows an upper respiratory tract infection 3) Systemic signs of infection: high fever, shaking chills, pleuritic chest pain 4) Local signs of irritation: productive mucopurulent cough 5) Airway obstruction: shortness of breath (dyspnea), rapid breathing (tachypnea) 6) Occasional patients may have hemoptysis

Question 38

1) World’s foremost cause of death from a single infectious agent is what? 2) What is the etiology of this Dx? How is it transmitted?

Answer 38

1) TB 2) Mycobacterium tuberculosis (rod-shaped bacterium with waxy capsule); airborne

Question 39

TB: 1) Is it communicable? Explain 2) What organ(s) are involved?

Answer 39

1) A communicable chronic granulomatous disease; centers of tubercular granulomas undergo caseous necrosis 2) Usually involves lungs, but may affect any organ

Question 40

Primary Pulmonary Tuberculosis: 1) What is it? Describe it 2) How common is it?

Answer 40

1) Primary infection in previously unexposed unsensitized patient Localized infection in lung and regional lymph nodes Ghon complex heals spontaneously by calcification and scarring 2) Progressive primary TB rare, only 5% newly infected acquire significant disease (mainly children, immunosuppressed individuals)

Question 41

1) Secondary tuberculosis can result from what 2 things? 2) What are its typical characteristics?

Answer 41

1) Dormant primary infection or a re-infection by M. tuberculosis 2) Bacteria typically spread to apex of lungs, causing granulomatous bronchopneumonia -Confluent granulomas produce **cavities**

Question 42

Secondary Pulmonary Tuberculosis: 1) Pulmonary cavities are sources of what? 2) Tissue destruction ensues, and occasional bacterial spread. What are 3 potential conditions that can result from this?

Answer 42

1) Hemoptysis 1) Tuberculous pneumonia, Extrapulmonary tuberculosis, or Miliary tuberculosis (system wide)

Question 43

Both progressive primary tuberculosis and secondary tuberculosis can result in what? What does this cause?

Answer 43

1) Systemic seeding 2) Life-threatening forms of disease such as miliary tuberculosis and tuberculous meningitis.

Question 44

What is an important risk factor for the development or recrudescence of active tuberculosis?

Answer 44

HIV-seropositive status.

Question 45

Secondary tuberculosis 1) Usually occurs where? 2) Sx? 3) What is needed to Dx? How is it definitively established?

Answer 45

1) Secondary tuberculosis-usually in the apices 2) Nonproductive cough, low-grade fever, loss of appetite, malaise, night sweats, weight loss, hemoptysis Chest X-rays essential for diagnosis 3) By identifying bacilli in sputum by acid-fast stains

Question 46

1) What is the most important cause of cancer related deaths in industrialized countries, that is also the leading cancer killer in men and women in U.S? 2) What is the most important risk factor? 3) At diagnosis, ___% of people have distant mets 4) Describe the survivability of this condition.

Answer 46

1) Carcinomas of the Lung 2) Smoking 3) 50% 4) Five-year survival rate is 16%, but is 45% for cases detected when the disease is still localized (within the lungs)

Question 47

What are the four major histologic subtypes of lung carcinoma?

Answer 47

1) Adenocarcinoma (most common) 2) Squamous cell carcinoma 3) Small-cell carcinoma (sub-type of neuroendocrine tumor) 4) Large-cell carcinoma

Question 48

Clinical Features of Lung Cancer: 1) Initial Sx? 2) Subsequent Sx (w. poor prognosis)? 3) Symptoms of metastatic spread can be presenting complaint, like what?

Answer 48

1) Cough & expectoration 2) Hoarseness Chest pain Superior vena cava syndrome Pericardial or pleural effusions 3) Brain- mental or neurologic changes Liver – hepatomegaly Bone-pain

Question 49

Malignant Mesothelioma: 1) What is it? 2) What is it highlight related to? 3) What is the latent period? What is it secondary to? 4) Describe why it occurs

Answer 49

1) Rare CA of the mesothelial cells of visceral or parietal pleura 2) Airborne asbestos (80-90%) 3) From exposure to development = 25-40 years; secondary to causative driver mutations 4) Once inhaled, asbestos fibers remain for live and do not diminish over time (as with cessation of smoking)

Question 50

Pleural effusions: Differentiate between transudate and exudate

Answer 50

1) Transudate → “hydrothorax” -Most common cause: CHF 2) Exudate → defined as protein >30 g/L -Microbial invasion (direct extension of pulmonary infection or blood-borne seeding) -Cancer: ie lung carcinoma, metastatic neoplasms, mesothelioma -Pulmonary infarction -Viral Pleuritis

Question 51

Cystic fibrosis: 1) What is CF? 2) What is affected by the disease?

Answer 51

1) An autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene 2) The CFTR protein chloride channel located in the apical membrane of the epithelial cells (lung, pancreas, sweat gland, vas deferens)

Question 52

1) The major features of classic cystic fibrosis are what 2 things? 2) Although CF has been observed in all races, it is predominantly a disease of what group?

Answer 52

1) Chronic pulmonary disease and malabsorption 2) Northern Europeans, with an incidence of approximately 1 in 2500 Caucasian births

Question 53

Pathogenesis of CF: 1) What does the CFTR protein do? 2) What happens in CF pts?

Answer 53

1) Maintains the hydration of secretions within the airways and ducts through the transport of chloride across the cell membrane and inhibition of sodium uptake 2) The chloride channel is unable to open causing chloride ions to accumulate in the cell. To balance the chloride ions, the cells absorb excess sodium. In secretory glands, this leads to decreases in fluid production.

Question 54

CF pathogenesis: 1) Loss of CFTR chloride transport into the pancreatic duct impairs what? What does this lead to? Explain. 2) What follows all of this?

Answer 54

1) Hydration of secretions and leads to the retention of exocrine enzymes in the pancreas. Damage from these retained enzymes eventually causes fibrosis of the pancreas. 2) Without proper pancreatic enzyme action, malabsorption follows

Question 55

CF pathogenesis: 1) CFTR also regulates the uptake of what? 2) What happens when the uptake can't happen because of a non-functional CFTR?

Answer 55

1) Sodium and chloride from sweat as it moves through the sweat duct 2) The sweat has an increased sodium chloride content, and this is the basis of the historical "salty baby syndrome" and the diagnostic sweat chloride test

Question 56

CF Phenotype and Natural History: 1) CF classically manifests in early childhood, although approximately ___% of patients are diagnosed in adulthood. 2) At birth, most infants present with what? Describe. 3) CF patients have poor growth; why?

Answer 56

1) 4% 2) Most present w. chronic respiratory complaints; 15-20% present with meconium ileus due to thickened meconium or failure to pass meconium 3) Combination of increased calorie expenditure because of chronic lung infections and malnutrition from pancreatic exocrine insufficiency

Question 57

CF: 1) More than _____% of male patients with CF are azoospermic because of congenital bilateral absence of the vas deferens (CBAVD). 2) What is the chief determinant of morbidity and mortality? 3) The current average survival is ___ years of age in the United States

Answer 57

1) 95% 2) The progression of lung disease 3) 37

Question 58

CF Phenotype and Natural History: 1) A correlation between particular CFTR mutant alleles and disease severity exists only for what? 2) What markedly worsen the severity of lung disease among patients with CF?

Answer 58

1) Pancreatic insufficiency 2) Environmental factors (like exposure to cigarette smoke)

Question 59

How can CF be managed? (both lung and pancreatic Sx)

Answer 59

1) Pulmonary physical therapy and use of bronchodilators, antibiotics, and mucolytic agents to manage pulmonary disease 2) In those with pancreatic insufficiency, oral enzyme replacement is provided

Question 60

CF Inheritance Risk: 1) Two heterozygous carrier parents have a ____% risk of having a child with cystic fibrosis. 2) The heterozygous carrier frequency in the White population is approximately what? 3) There are newborn screenings for cystic fibrosis where? Explain

Answer 60

1) 25% risk of having a child with cystic fibrosis 2) 1 in 50 3) All 50 states -In many regions, carrier screening is provided based on detection of the most common CFTR mutations