The slides for the Pathology Assistants.

1. January 26, 2016
Mahra Nourbakhsh, MD, PhD

2.  Respiratory system is composed of:
1. Thoracic walls:
 Bones (ribs, sternum and thoracic vertebra), Nerves, Vessels
2. Extraparenchymal airways:
 Larynx, Trachea
3. Pleura:
 Visceral and Parietal
4. Lungs:
 Left and Right lungs, Airways (Intraparenchymal), Vascular
tissue and Interstitial tissue

3. Body of
sternum
Xiphoid
process
Costal cartilages
(hyaline cartilage)
Manubrium
sterni
 12 Ribs
 Attachment:
 Posteriorly: to transverse
process of 12 thoracic
vertebrae
 Anteriorly: directly or
indirectly to sternum.

4.  Major Muscles of Respiration
 Diaphragm, Intercostal muscles
 Accessory Muscles of Respiration:
 SCM, Scalen, abdominal wall muscles, serratus ,etc.

5. Trachea
Trachea:
 Length: 10-16 cm
 Diameter: 25mm
 Formed by: C-shape cartilage
and trachealis muscles.
 Divide to left & right main
(primary) bronchus at carina to
left & right lung.
 Lobar (Secondary) bronchus: to
superior/inferior lobes on the
left lung and
superior/middle/inferior lobes
on the right lung
 segmental (tertiary) bronchus

6.  Visceral Pleura: attached to the surface of the lung and continues inside the
fissures.
 Parietal pleura: attached to the chest wall (coastal pleura), diaphragm
(diaphragmatic pleura) and mediastinum (mediastinal pleura).

7. Pleural Cavity:
 Slit like potential space that separates visceral
from parietal pleura.
 Contains very scant amount of fluid.
 Has negative pressure in comparison to air
pressure, opens the lung. If the negative
pressure is disturbed, the lung will collapse
Pleural Reflections:
 At the lung base parietal pleura is two
intercostal space lower than visceral pleura.
 Costophrenic (Costodiaphragmatic) recess, the
first place you see the fluid in upright CXRay.
Q1: What is pleural effusion? What is empyema? Where do they accumulate

8.  Penetration of air or blood inside the pleural cavity disturbs the negative
pressure of pleural cavity, potentially life threatening.
 Collapsed lung, reduction of blood return to the right heart and consequently
hypotension.
Air in pleural space
blood in
pleural
space
What is the diagnosis in these two cases, both resulting from trauma?

9. • Left lung: one fissure (oblique), two lobes (upper and lower) and two lobar
bronchus (upper and lower) and arteries
• Right lung: two fissure (oblique and horizontal) and three lobes (upper, middle,
lower) and three lobar bronchus and arteries.
• Each lobe: has segments and segmental bronchus and arteries.

10.  Pulmonary circulation: gas exchange with outside air
 Bronchial (systemic) circulation: supply the lung parenchyma.
 No pain receptors in parenchyma.
 Pain receptors can be found in parietal pleura and vasculature of
the lung

11.  Explain why early lung parenchymal tumors are
painless? When do you think lung tumors can cause
pain?
 When does pneumonia can cause chest pain?
 Explain why pulmonary emboli and pulmonary
hypertension are associated with chest pain?
 What is pleuretic chest pain? How do you differentiate
pleuretic chest pain from other type of chest pain?

12. 1. History  symptoms
2. Physical exam  signs
3. Differential diagnosis:
4. Assessment and plan:

13.  Definition: Unpleasant subjective sensation of
breathing.
 DDX: Apart from pulmonary causes, cardiac,
psychiatric, hematologic and neuromuscular causes
disease can cause dyspnea.
 Pulmonary causes: almost any type of pulmonary
disease can cause dyspnea.

14.  Definition: sharp chest pain associated with respiration
and is aggravated by deep inspiration.
 DDX of pleuretic chest pain: any disease that primarily
(pleuritis, rib fracture) or secondarily (lung tumors,
pneumonia, affects parietal pleura and/or chest wall.

15.  Productive vs. dry cough
 DDX:
1. Airway irritants: fume, GERD, nasal discharge
2. Airway disease:
3. Parenchymal disease:
4. CHF
5. Drug induced

16.  Definition: expectoration of blood from respiratory
system arises from alveoli to glottis.
 Massive henoptysis: >600 ml/24h, life threatening
 DDX:
1. Epistaxis
2. Airway disease: Chronic bronchitis
3. Parenchymal disease: Pneumonia
4. Vascular disease: PE
5. Miscellaneous: TB, Tumor

17.  Wheezing: Low pitch continuous musical sounds
 Rales/Crackles: Short explosive sounds
Click and hear example of abnormal breath sounds

18.  Standard (upright): Posterior-Anterior (PA) and
Lateral (Lat).
 Supine: Anterior-Posterior (AP) for bed-ridden
patients.
 Lateral Decubitus: Left& Right, for pleural
effusion.

19. PA vs AP film: Note the difference in size of the heartPA vs Lat decubtous: Note fluid is moving with gravity

20.  X ray-based technique
 X-ray source and detector
rotate around the body
provide 3D pictures.
 Very sensitive technique for
detecting small size tumor or
looking to interstitial diseases
 Sensitivity can be increased by
using contrast.

21. CT scan can detect the mass that are not visible on CXR
CT scan detects PE
High Resolution CT (HRCT) scan is the preferred radiologic method for
interstitial lung disease, in this case idiopathic pulmonary fibrosis

22.  No Xray, no radiotracer, therefore safer
technique specifically in pregnant women
 Very high resolution.
 Application of MRI is limited in intrinsic lung
disease due to signal loss by physiologic
movement of chest during respiration.
 Excellent imaging modalities for chest
wall/diaphragmatic tumors

23.  Functional imaging technique, using radiotracer
which emits gamma ray.
 A tracer is typically a biologically active
derivatives of glucose called fluorodeoxyglucose
(FDG) that is absorbed by metabolically active
tissue (in this case neoplasm).
 The imaging is done by help of CT Scanner (PET-
CT), therefore not only is an anatomic imaging
but also is a functional imaging.
FDG avid mass high possibility of neoplasm

24.  Majority of pulmonary diseases are associated with
alteration in arterial oxygen pressure (PaO2), CO2
(PaCO2) and consequently acid-base status.
 ABG provides information regarding oxygenation and
acid-base status rapidly.
 Four important components of ABG are pH, HCO3,
PaO2 and PaCO2.

25.  Collection of sputum
 Percutaneous Transthoracic Needle Aspiration: Under
guide of US or CT Scan a large needle is inserted
through the chest wall into the lesion to obtain
specimen for histology or microbiology
 Thoracentesis: Blind or under US guide a needle is
inserted into the pleural cavity to collect fluid. The
specimen is sent for microbiology, cytology and
biochemical assays. It is also therapeutic

26.  Endoscopic technique to visualize inside the airways
Rigid
Flexible

27.  Transbronchial biopsy: Can be performed using biopsy forceps
passing through the bronchoscope
 Brushing: another way for obtaining small size biopsy
 Bronchoalvelar lavage (BAL): With the bronchoscope wedged into
a sub-segmental airway, aliquots of sterile saline can be instilled
through the scope allowing sampling of cells and organisms from
alveolar spaces.
 Endobronchial ultrasound and transbronchial needle aspiration:
an ultrasound probe fitted in bronchoscope is used as a guide for
needle aspiration of a mass

28.  Medical Thoracoscopy: using rigid or semi-rigid thoracoscope
visulaize the pleural cavity. Biopsy can taken from parietal pleura
 Video Assissted Thoracoscopic Surgery: Performs at OR using a
thoracoscope, surgeon can take biopsy from lung or visceral
pleura, reduces the need for thoracotomy.
 Open lung biopsy: thoracotomy

29.  Using spirometer multiple maneuver including
inspiration and expiration is performed and the
machine measures volume of exchanged air and flow
(volume/sec) of exchanged air.

30. Total Lung Capacity (TLC): the volume in the lung at maximum inflation
Residual Volume (RV): the volume of remains in the lung after maximum exhalation.
Vital Capacity (FVC): the volume that is exhaled out after the deepest inhalation.
Forces Expiratory Volume at 1 second (FEV1): the volume is breathed out in the first
second of exhalation by force

31.  Obstructive: the hallmark is air entrapment in the lung,
therefore the RV and TLC is increased. In addition due
to obstruction less air is exhaled out there fore the
FEV1 is reduced. FVC is slightly reduced, therefore
FEV1/FVC is reduced significantly.
 Restrictive: the hallmark is that air cannot enter to the
lung due to the reduced lung elastic recoil (stiff lung) or
weak inspiratory muscles, therefore the RV and TLC is
reduced. FEV1 remains normal or slightly reduced but
FVC is extremely reduced. Therefore FEV1/FVC is
increased significantly.

32. FVC

33.  The PFT results of three patients are as follow.
What pattern of lung disease do they have?
 Patient #1: RV=123%, TLC= 128%, FEV1=56%
and FVC=89% of the normal values.
 Patient #2: RV= 69%, TLC=72%, FEV1=95% and
FVC=62% of the normal values.

34.  Reversible Obstruction:
1. Asthma
 Irreversible Obstruction:
1. Chronic Obstructive Pulmonary Disease:
Emphysema and Chronic Bronchitis
2. Bronchiectasis
3. Cystic Fibrosis

35.  Definition: Reversible bronchospasm due to inflammation
causing airflow obstruction..
 Sign and symptoms: Triad of dyspnea, cough and wheezing. Can
cause cyanosis and respiratory distress
 Diagnosis: in acute attack the diagnosis is clinical. But after
stabilization, obstructive pattern on PFT which is reversed by
using bronchodilators (ventolin).
 Chracot-Leyden Crystals: produced after eosinophil enzyme
(lysophospholipase) is released.
 Curschmann’s spirals: spiral shape mucus plugs found in sputum
of asthmatic patients
 Treatment: Bronchodilators (short acting and long acting),
corticosteroids (inhaler and systemic), Leukotriene Receptor
Antagonists and Anti IgE.

36.  Chronic Bronchitis
 Productive cough on most days for at least 3 consecutive
months in two consecutive years.
 Obstruction is due to narrowing of airway lumen by excess
mucus and thickened mucosal wall.
 Emphysema
 Dilation and destruction of air spaces distal to terminal
bronchiole.
 Decrease elastic recoil of lung parenchyma causes
decreased expiratory driving pressure, airway collapse and
air trapping.
 Two types: Centriacinal in smokers mostly upper zone and
Panacinar in alpha-1 antitrypsin deficiency, lower lobes.

37.  Chronic Bronchitis (Blue Bloater)
 Chronic productive cough, purulent sputum, hemoptysis,
mild dyspnea initially.
 Cyanosis, crackle, wheezing, frequently obese.
 Emphysema (Pink Puffer)
 Dyspnea, tachypnea, minimal cough.
 Pink skin, pursed-lip breathing, hyperinflation of lung/barrel
chest, decreased breath sounds, cachectic.

38.  Chronic Bronchitis
 Major risk factor is smoking.
 Diagnosis: Clinical + PFT.
 Treatment: O2 (increase the survival), bronchodilators,
corticosteroids
 Emphysema
 Major risk factor is smoking. Also alpha-1 antitrypsin
deficiency can cause emphysema
 Diagnosis: Clinical, PFT + CXR.
 Treatment: O2 (increase the survival), bronchodilators,
corticosteroids

39.  Markedly dilation of airway is the hallmark of
the emphysema. Bullae are markedly enlarged
air space (> 1cm in diameter) which is believed
to arise from ball-valve mechanism resulting
more air entrapment. They can be seen in
CXRay

40.  Definition: Irreversible dilation of airway due to
inflammatory destruction of airway wall resulting from
persistently infected mucus
 Risk Factors:
1. Post infection:
2. Post obstruction:
3. Impaired defenses:
 Sign and Symptoms: chronic cough, purulent sputum,
hemoptysis, recurrent pneumonia, local crackle and
wheezing

41.  Diagnosis: PFT+ HRCT
 Treatment: Vaccination, antibiotics,
corticosteroids, chest physio and pulmonary
resection.

42.  Genetic disease due to mutation in the gene cystic fibrosis
transmembrane conductance regulator (CFTR). The most
common mutation is deletion of 3 nucleotide results in deletion
of phenylalanine at position 508.
 Pathophysiology: Chloride transport dysfunction: thick secretion
from exocrine glands (lung, pancreas, skin, reproductive organs)
and blockage of secretory ducts.
 Lung: clogging of the airway by thick mucus build-up and
obstruction later recurrent infection, bronchiectasis. The
most common cause of death is secondary to respiratory
failure.
 Pancreas: pancreatic deficiency
 Other manifestation: Diabetes, azoospermia, sinusitis,
meconium ileus in infants.

43.  Diagnosis: Sweat chloride test, PFT, Genetic
counseling.
 Treatment: there is no cure. Treatment is
supportive by using chest physiotherapy,
bronchodilators, mucolytics, inhaled
tobramycin, antibiotics, pancreatic enzyme
supplement.
 Lung transplantation: disease progresses in the
transplanted lung

44.  Is asthma always an allergic response?
 Name four pulmonary obstructive diseases.
 What is the only treatment with mortality
benefits in chronic bronchitis and emphysema?

45.  Inflammation and/or fibrosing process in the alveolar walls
results in thickening and fibrosis of the interstitial tissue
 Sign and Symptoms: Dyspnea on exertion, dry crackles, non-
productive cough, cyanosis, clubbing
 Diagnosis: Radiology (HRCT), PFT, Bronchoscopy, BAL, Biopsy

46. 1. Known:
 Systemic Rheumatic Disorders: RA, Scleroderma, SLE, etc.
 Drugs
 Pulmonary vasculitis: Wegner’s granulomatosis, churg-
strauss, etc.
 Environment/Occupation
 Alveolar filling disorders: Goodpasture, diffuse alveolar
hemorrhage, .pulmonary alveolar proteinosis
2. Unknown:
 Idiopathic pulmonary fibrosis (IPF), Sarcoidosis, Langerhans-
cell histocytosis, lymphangiolyomyomatosis, pulmonary
infiltrates with eosinophilia, non-specific interstitial
pneumonia, lymphocytic interstitial pneumonia and
cryptogenic organizing pneumonia.
Do not memorize the followings

47.  Hypersensitivity pneumonitis: also known as
extrinsic allergic alveolitis secondary to intense and
repetative sensitization and exposure to an organic
agents. Example: Farmer’s lung, bird breeder’s lung,
etc.
 Pneumoconioses:
 Asbestosis
 Silicosis
 Coal worker pneumoconiosis.

48.  Exposure to several forms of mineral silicate called asbestos that
was used as a thermal insulator.
 The asbestos fibers are inhaled and induces lung fibrosis.
 Lots of people are not fully aware that they have been exposed.
Even bystander exposure can cause asbestosis.
 Pleural plaques specifically at lower lobes and diaphragmatic
surface can be seen on CXR.
 PFT reveals restrictive pattern.
 Most common cancer  Bronchogenic carcinoma, minimum
latency of 15-19 years, increased risk if also smoking
 Mesothelioma of pleura or peritoneal are associated with
exposure. 80% of mesothelioma is related to mesothelioma
therefore can be compensable. Relatively short–term exposure
(<1-2 years) occurring up to 40 years in the past .

50.  Definition: non-caseating granulomatous inflammatory disease.
 Etiology: Unknown. Infection vs environmental agent.
 Epidemiology: more common in African American than whites
and female than male.
 Clinical manifestations: Fever, fatigue, cough, constitutional
symptoms.
1. Lung: involved in 90% of patients, restirctive pattern but
also can shows obstructive pattern
2. Skin: Lupus Pernio, erythema nodosum, etc.
3. Eye: anterior uveitis but also can involve the porsterior of
the eyes as well.
4. Liver:
5. Calcium metabolism : Hypercalcemia
6. Other organs: Bone marrow, renal, cardiac,
musculoskeletal, testes, ovary

51.  Diagnosis: Sarcoidosis is diagnosed based on clinical
manifestations, characteristic CXR findings and biopsy but in
general the diagnosis cannot be made with 100% certainty. The
following findings can help in diagnosis
1. Serum levels of angiotensin converting enzyme (ACE)
2. Hypercalcemia
3. Biopsy: non-caseating granuloma
4. CXRay: Standard scoring system
 Stage 1: hilar lymphadenopathy
 Stage 2: hilar lymphadenopathy + lung infiltrates
 Stage 3: lung infiltrates
 Stage 4: fibrosis

52.  Clinical course: Usually self-limited, non-life
threatening disease but can progress to
pulmonary fibrosis, pulmonary arterial
hypertension, right ventricular failure and
death.
 Treatment: Glucocorticoids, cytotoxics and
biologics drugs such as methotroxate,
azathioprine, cyclophosphamid

53.  What is the most common cancer associated
with asbestosis?
 A second year pathology resident observed a
non-caseating granuloma in a lung specimen.
He wrote the sarcoidosis as the diagnosis in the
report. Do you have any advice for him?

54.  Epidemiology:
 The leading cause of death due to cancer, mortality three
times more than prostate cancer, two times more than
breast cancer.
 Rare below age of 40
 The projected lifetime probability of developing lung cancer
is 8% among the man and 6% among the women.
 Risk Factor:
 Smoking: 20 times increased risk, 1 mutation per cigarette smoking,
second hand smoker 20-30% increased chance.
 Occupational and environmental exposure: to asbestos, arsenic, nickel,
aromatic hydrocarbons, radon, ionizing radiation.
 Inherited predisposition to lung cancer

55.  Clinical manifestations:
 Over half of the patients diagnosed with locally advanced or
metastatic disease.
 There isn’t any good screening test that results in reduction
of the mortality.
 Majority of symptoms are related to local growth (cough,
pneumonia), extension to the adjacent structure (pleural
effusion, dysphagia, chest pain, horner’s syndrome),
paraneoplastic syndromes or constitutional symptoms
(weight loss, etc).
 Diagnosis:
 CXR, CT is the primary tests but eventually the diagnosis is
based on biopsy

56.  Epithelial Tumors:
 Adenocarcinoma
 Squamous cell carcinoma
 Large cell carcinoma
 Neuroendocrine tumors including small cell
carcinoma
 Other types
 Mesenchymal Tumors
 Lymphohistocytic tumors
 Tumors of ectopic origin
 Metastatic tumors

57.  Treatment:
 Surgery:
 Non-small cell lung cancer: in early stages and in non
small cell lung cancer, lobectomy, pneumonectomy
 Small cell lung cancer: are extremely aggressive with
micrometastasis in time of diagnosis and very sensitive to
chemo, therefore surgery is not performed
 Chemotherapy: target therapy is evolving, for
example (EGFR mutation)
 Radiotherapy

58.  Definition: infection of pulmonary parenchyma
 Classification:
 Community-acquired pneumonia (CAP)
 Hospital-acquired pneumonia (HAP)
 Ventilator-associated pneumonia (VAP)
 Health care-associated pneumonia (HCAP)
 Typical vs Atypical pneumonia:
 Typical pneumonia (lobar): high grade fever, productive
cough, consolidation on CXR.
 Atypical pneumonia (interstitial): fever, non-productive
cough, non-respiratory symptoms, increase interstitial
marking on CXR

59.  Common etiologic agents of CAP:
 Typical bacterial agents: S. Pneumonia, H .Influenza, S.
auerus, Klebsiella pneumoniae, P. aeruginosa
 Atypical Bacterial agents: Mycoplasma pneumonia,
chlamydia pneumonia, legionella
 Mycobacterium: MTB
 Virus: causes atypical pneumonia, influenza, adenovirus,
human metapneumovirus, RSV.
 Fungi: H. Capsulatum
 Diagnosis: Clinical + CXR, blood culture, sputum culture, BAL PCR
on nasopharyngeal swabs, serology, urinary antigen test
Do not memorize the followings

60.  Common etiologic agents of VAP:
 Non-multidrug resistant pathogens: S. Pneumonia, H
.Influenza, MSSA,
 Multi drug resistant pathogen: p. aeruginosa, MRSA,
legionella.
 Fungi: Aspergilus.
 Common etiologic agents of HAP:
 Similar to VAP but also presence of anaerobe due to
aspiration pneumonia
 Diagnosis: similar as CAP
Do not memorize the followings