Respiratory Pathology and Pathophysiology and Clinical Presentation

1. Respiratory Pathology
and Pathophysiology
“With disease presentation and clinical implications”
Companions:
Recommended Reading:
Pulmonary
Pharmacology (Asthma)
Pharm Formative
Assessment
Practice question set #1
Clinical:
e-Medicine Article
Asthma
Prepared and presented by
Marc Imhotep Cray, M.D.
BMS/CK Teacher
Chest X-ray of a person with advanced
tuberculosis

2. 2
Pulmonary Pathology
Sections of the WebPath images are available for viewing by organ
system. Each section consists of a series of images demonstrating gross
and microscopic pathologic findings for a variety of disease processes. A
short description accompanies each image.
Internet Pathology Laboratory
for Medical Education
http://library.med.utah.edu/WebPath/webpath.html#MENU
IVMS USMLE Step 1 Prep.
Towards Understanding the Basic Medical Sciences Foundation of
Clinical Medicine
IVMS teaching philosophy is based on the integration of basic and
clinical sciences...Learn More

3. Objectives
• Understand presenting symptoms suggestive
of pulmonary disease
• Understand pathophysiology, pathology,
disease presentation, implications, and
treatment of major pulmonary diseases
including, COPD, Restrictive lung disease,
asthma, Cystic Fibrosis, and lung cancers
IVMS USMLE Step 1 Prep. 3

4. Presenting Symptoms
• Cough
– Acute: viral or bacterial bronchitis, URI, or
pneumonia
– Chronic: asthma, postnasal drip, bronchitis,
GERD
• Hemoptysis
– Ask the patient to estimate the amount of blood
– Distinguish between epistaxis, hematemesis, and
hemoptysis
IVMS USMLE Step 1 Prep. 4

5. Presenting Symptoms (2)
• Dyspnea
– Timing, acuity of onset, exacerbating and
alleviating factors, degree of functional
impairment
– Acute (p.e.) vs chronic (COPD)
– Exertional or resting, episodic or continuous
– Paroxysmal nocturnal dyspnea
– Orthopnea
IVMS USMLE Step 1 Prep. 5

6. Presenting Symptoms (3)
• Chest pain
– Many causes (cardiac, pulmonary, GI,
musculoskeletal, etc)
– Pulmonary causes: pleural disease, pulmonary
vascular disease, musculoskeletal
• lung parenchyma has no pain fibers
– Pleuritic chest pain: sharp or stabbing pain on
inspiration that can be positional
IVMS USMLE Step 1 Prep. 6

7. Other important history
• Cigarette smoking
– Quantified as # of packs smoked/d X # of
cumulative years (60pk year = 1 ppd X 60yrs)
– Risk of lung disease is directly related to # of pack-
years exposure and inversely to age at onset of
smoking
• Other environmental exposures, travel
• Family history (CF, alpha-1 antitrypsin
deficiency)
IVMS USMLE Step 1 Prep. 7

8. Physical Exam
• Watch the patient breath
• RR, use of accessory muscles, paradoxical
abdominal breathing, ability to speak in full
sentences
• Shape of the patient’s chest cavity
– AP diameter suggestive of COPD
• Auscultation
–Rhonchi, rales, wheezing, rub
• Clubbing
IVMS USMLE Step 1 Prep. 8

9. Respiratory Infections
• Upper respiratory infection
– Most are viral: common cold, pharyngitis, etc
• Lower respiratory infection
– Frequently viral
– Bronchitis: cough, wheezing, dyspnea
– Pneumonia: cough, fever, rapid resp, dyspnea
IVMS USMLE Step 1 Prep. 9

10. Pneumonias
IVMS USMLE Step 1 Prep. 10
Compare the diffuse, patchy bilateral infiltrates of “atypical” interstitial
pneumonia (A) with the localized, dense lesion of lobar pneumonia (B)
Source: First Aid for the USMLE Step 1 2008, pg. 435

11. Pneumonias (2): Classification
IVMS USMLE Step 1 Prep. 11
Source: First Aid for the USMLE Step 1 2008, pg. 468

12. Pneumonias (3): Gross and
histopathology
•Lung, bronchopneumonia, gross [XRAY]
•Lung, bronchopneumonia, gross
•Lung, bronchopneumonia, gross
•Lung, lobar pneumonia, gross
•Lung, empyema, gross
•Lung, abscesses, gross
•Lung, abscesses, gross
•Lung, abscessing bronchopneumonia, gross
•Lung, bronchopneumonia, low power microscopic
•Lung, bronchopneumonina, high power microscopic
•Lung, bronchopneumnia, high power microscopic
•Lung, abscessing pneumonia, low power microscopic
•Lung, abscessing pneumonia, high power microscopic
•Lung, aspiration pneumonia, low power microscopic
•Lung, aspiration pneumonia, high power microscopic
•Lung, chronic abscess, gross
IVMS USMLE Step 1 Prep. 12

13. Pulmonary Tuberculosis
13
http://emedicine.medscape.com/article/230802-overview
Chandrasoma P, Taylor CR. Concise Pathology, 3rd ed. Stamford, CT: Appleton
& Lange, 1998: 523 IVMS USMLE Step 1 Prep.

14. Pulmonary Tuberculosis (2)
14
http://upload.wikimedia.org/wikipedia/commons/2/2f/Tuberculosis_symptoms.svg
IVMS USMLE Step 1 Prep.

15. Pulmonary Tuberculosis (3)
• Caused by Mycobacterium tuberculosis
• Major global problem; Seen in pts with
HIV, other immunocompromised states,
developing countries, etc
• Contracted by inhalation
Diagnosis suggested by:
• chronic cough,
• hemoptysis,
• weight loss,
• fevers,
• night sweats M. tuberculosis bacterial colonies
http://upload.wikimedia.org/wikipedia/co
mmons/0/0a/TB_Culture.jpg
Scanning electron micrograph of
Mycobacterium tuberculosis
IVMS USMLE Step 1 Prep. 15

16. Pulmonary TB (4)
• Diagnosis: confirmed by CXR, PPD, sputum
smears and culture
Chest X-ray of a person with advanced tuberculosis
http://upload.wikimedia.org/wikipedia/commons/9/9c/Tub
erculosis-x-ray-1.jpg
Mycobacterium tuberculosis Ziehl-Neelsen stain
IVMS USMLE Step 1 Prep. 16
Treatment: 4 drug therapy
See Tuberculosis Treatment & Management
http://emedicine.medscape.com/article/230802-
treatment

17. Obstructive Lung Disease
General
• Obstruction of air flow through airways
• Major causes:
– asthma
– bronchiectasis,
– emphysema and bronchitis (COPD)
IVMS USMLE Step 1 Prep. 17
Obstructive lung disease (COPD) Obstruction of air flow resulting in air trapping in
the lungs. Airways close prematurely at high lung volumes, resulting in ↑ RV and ↓
FVC. PFTs: ↓↓ FEV1, ↓ FVC→ ↓ FEV1/FVC ratio (hallmark), V/Q mismatch.

18. Pathophysiology
• Air flow is decreased by: airway narrowing
and/or loss of elastic recoil of the lung
• Airway Narrowing
– Airway inflammation
• tobacco smoke, recurrent infection, immunologic
dysfunction
– Bronchoconstriction
IVMS USMLE Step 1 Prep. 18

19. Pathophysiology (2)
• Loss of elastic recoil
– COPD: loss of airway tone and decreased
tethering by surrounding lung
– Asthma: bronchoconstriction and mucus plugging
allowing airways to collapse at higher lung volumes
and trap excessive air
– Increased ventilation: increased airflow resistance
may not allow lungs to completely empty during
expiration
IVMS USMLE Step 1 Prep. 19

20. Bronchitis vs Emphysema
IVMS USMLE Step 1 Prep. 20
Source: First Aid for the USMLE Step 1 2008,pg 400

21. COPD
Gross and histopathology
•Lung, bronchiectasis, gross
•Lung, bronchiectasis, gross
•Lung, bronchiectasis and fibrous pleural adhesions, gross
•Lung, bronchiectasis, low power microscopic
•Lung, chronic bronchitis, medium power microscopic
•Lungs, bullous emphysema, gross
•Lung, centrilobular emphysema, gross
•Lung, centrilobular emphysema, gross
•Lung, emphysema, microscopic
IVMS USMLE Step 1 Prep. 21

22. COPD
• Slowly progressive, irreversible airway
obstruction
• Exacerbations of disease by bacterial/viral
infections, heart failure, lack of medicine use,
etc
• Characterized by dyspnea, sputum
production (with chronic bronchitis)
IVMS USMLE Step 1 Prep. 22

23. COPD: types
• Chronic bronchitis
– persistent cough with sputum production for
more than 3 months over last 3 years
• Emphysema
– abnormal enlargement of air spaces
– The degree of obstruction in patients with COPD
correlates more closely with severity of the
emphysema
IVMS USMLE Step 1 Prep. 23

24. COPD
• Physical Exam
–  AP diameter,  RR, clubbing
• Laboratory data;
– Pulmonary function test is sensitive way to make
diagnosis in early stages
– ABG: hypoxia, hypercarbia (advanced)
– CXR: hyperinflation, flattened diaphragms,
increased AP diameter, widened retrosternal air
space (with emphysema)
IVMS USMLE Step 1 Prep. 24

25. COPD: Clubbing
IVMS USMLE Step 1 Prep. 25

26. COPD: Hyperinflation
IVMS USMLE Step 1 Prep. 26

27. COPD
flattened diaphragms, lucency
IVMS USMLE Step 1 Prep. 27

28. COPD
• Treatment
– STOP smoking (if this is cause)
– Treat exacerbations of bronchitis with antibiotics
– Most meds have not been found to be helpful
– Ipratropium bromide MDI (atrovent MDI) is
helpful (anti-cholinergic)
– Steroids not usually helpful unless inflammatory
component
IVMS USMLE Step 1 Prep. 28

29. Asthma
Obstruction of the lumen of the bronchiole by mucoid exudate, goblet cell
metaplasia, epithelial basement membrane thickening and severe
inflammation of bronchiole in a patient with asthma.
IVMS USMLE Step 1 Prep. 29

30. Asthma (2)
• Chronic, inflammatory
disorder of the airways
• 3-5% of the population is
affected
• Imbalance between
proinflammatory and
inhibitory cytokines
• Episodic airway narrowing,
increased airway reactivity,
and reversibility
IVMS USMLE Step 1 Prep. 30
Gross and histopathology
•Lungs, hyperinflation with status
asthmaticus, gross
•Lung, cross section, hyperinflation
with status asthmaticus, gross
•Bronchial mucus plug with asthma,
gross
•Bronchial asthma, low power
microscopic
•Bronchial asthma, high power
microscopic

31. Asthma (3)
• Trigger: extrinsic allergens, intrinsic factors, or
no identifiable cause
• Types: extrinsic, intrinsic, exercise induced,
asa sensitive, occupational, ABPA
• Precipitants of asthma: postnasal drip, GERD,
cold exposure, gases/fumes, emotional stress,
hormones, resp infections
IVMS USMLE Step 1 Prep. 31

32. Asthma (4)
• Diagnosis (one or combination):
– wheeze, chronic episodic dyspnea, and chronic
cough
– Sputum production, chest pain or tightness
• Testing:
– History, CXR (to rule out other causes), pulmonary
function testing (with or without challenge)
IVMS USMLE Step 1 Prep. 32

33. Asthma (5)
• Treatment
– Education (removal of offending agents)
– Peak flow meters
– Inhaled corticosteroids (ex fluticasone)
– Long and short acting bronchodilators
• ex salmeterol, albuterol
– Leukotriene inhibitors (ex. montelukast)
– Theophylline (limited use)
IVMS USMLE Step 1 Prep. 33

34. Restrictive lung disease
IVMS USMLE Step 1 Prep. 34
Restricted lung expansion causes↓ lung volumes (↓ FVC and TLC). PFTs––
FEV1/FVC ratio > 80%.
Types:
1. Poor breathing mechanics (extrapulmonary, peripheral
hypoventilation):
a. Poor muscular effort––polio, myasthenia gravis
b. Poor structural apparatus––scoliosis, morbid obesity
2. Interstitial lung diseases (pulmonary, lowered diffusing capacity):
a. Adult respiratory distress syndrome (ARDS)
b. Neonatal respiratory distress syndrome (hyaline membrane disease)
c. Pneumoconioses (coal miner’s silicosis, asbestosis)
d. Sarcoidosis
e. Idiopathic pulmonary fibrosis (repeated cycles of lung injury and wound
healing with ↑ collagen)
f. Goodpasture’s syndrome
g. Wegener’s granulomatosis
h. Eosinophilic granuloma (histiocytosis X)
i. Drug toxicity (bleomycin, busulfan, amiodarone)

35. Cystic Fibrosis
IVMS USMLE Step 1 Prep. 35
Cystic fibrosis

36. Cystic Fibrosis(2)
• Autosomal recessive genetic
disorder
• Affects pulmonary, GI and GU
systems
• Most common lethal genetic
disorder
– 1/25 carrier frequency
– 1/3200 live births affected
• Defect: failure to produce normal
chloride channel leading to
increased sodium reabsorption 36
A breathing treatment for cystic fibrosis, using a mask
nebulizer and a ThAIRapy Vest

37. Cystic Fibrosis (3)
• Abnormal chloride channel leads to thick and viscous
secretions in the resp, hepatobiliary, gi, and reproductive tracts
• Resp tract: persistent inflammation and infection causes
bronchial wall destruction; mucus plugging of small airways
causing parenchymal destruction
– colonization by S. aureus, H. influenza, P. aeruginosa
37
http://en.wikipedia.org/wiki/File:Cystic_Fibrosis_Respiratory_Infections_by_Age.svg

38. Cystic Fibrosis (4)
• Testing
– Chloride sweat test
– Genetic testing
• Median survival
– 14 years in 1969 to >30 yrs since 1995
IVMS USMLE Step 1 Prep. 38

39. Cystic Fibrosis (5)
• Pathology
– Pulmonary: cough, sputum production, clubbing
– Upper Resp tract: nasal polyps, sinusitis
– GI: exocrine pancreatic dysfunction, diabetes,
cirrhosis, salivary gland inflammation
– GU: azoospermia, decreased fertility rate in
women, nephrolithiasis
IVMS USMLE Step 1 Prep. 39

40. Cystic Fibrosis(6)
• Treatment;
– Aggressive airway hygiene
– Nutritional support including pancreatic enzyme
replacement
– Antibiotics
– Bronchodilators
IVMS USMLE Step 1 Prep. 40

41. Lung Cancer
IVMS USMLE Step 1 Prep. 41
Squamous cell carcinoma in the right lower lobe
Source: First Aid for the USMLE Step 1 2008, pg. 434
Lung cancer is a leading cause of cancer death. Presentation:
cough, hemoptysis, bronchial obstruction, wheezing, pneumonic
“coin” lesion on x-ray film

42. Lung Cancer (2)
• Risk Factors
– Leading cause of death
– Cigarette smoking is responsible for >90% of lung
cancers
– Risk increases with dose and length of exposure to
cigarette smoking
– Heavy occupational exposure to asbestos is
second most important cause
IVMS USMLE Step 1 Prep. 42

43. Lung Cancer: Types
• Bronchial carcinoid tumors
• Small cell cancer
• Non-small cell cancer
– Squamous cell cancer
– Adenocarcinoma
– Large cell
– Anaplastic carcinoma
• Metastasis: breast, liver, renal, colon
IVMS USMLE Step 1 Prep. 43

44. Lung Cancer: Types (2)
IVMS USMLE Step 1 Prep. 44
Source: First Aid for the USMLE Step 1 2008, pg. 443

45. Lung Cancer
Gross and histopathology
•Lung, squamous cell carcinoma, gross [CT]
•Lung, squamous cell carcinoma, gross [XRAY]
•Lung, squamous cell carcinoma, medium power microscopic
•Lung, squamous cell carcinoma, high power microscopic
•Lung, peripheral adenocarcinoma, gross
•Lung, bronchioloalveolar carcinoma, gross
•Lung, bronchioloalveolar carcinoma, microscopic
•Lung, oat cell carcinoma, gross
•Lung, oat cell carcinoma, high power microscopic
•Lung, hamartoma, gross
•Lung, hamartoma, microscopic
•Lung, metastatic carcinoma, gross [XRAY]
•Lung, metastatic carcinoma, microscopic
•Pleura, metastatic carcinoma, microscopic
•Lung, mesothelioma, gross
•Lung, mesothelioma, high power microscopic
IVMS USMLE Step 1 Prep. 45

46. Lung Cancer: Clinical Presentation
• Symptoms can be quite non-specific
• Symptoms may relate to location and size of
tumor
– Cough, hemoptysis, post-obstructive pneumonia,
chest pain, wheezing, hoarseness
– bone metastases: swelling, pain
– hepatic metastases: jaundice, hepatomegaly
– weight loss, anorexia
IVMS USMLE Step 1 Prep. 46

47. Lung Cancer: Evaluation
• History and physical examination
• CXR/CT scan
• No lab is helpful
• Bronchoscopy
• VATS
IVMS USMLE Step 1 Prep. 47

48. Lung Cancer: Treatment
• Options depend on tumor type, size, stage of
disease, and performance status of the pt
• Surgical removal with Stage I, II, IIIA non-small
cell cancer (if operable)
• Chemotherapy with radiation for limited
stage disease in small cell cancer
– frequent metastases to the brain
IVMS USMLE Step 1 Prep. 48

49. Lung Cancer: Survival
• 15-25% survival 5 years after the diagnosis
• Considerable debate about screening for lung
cancer
– recent discussion on chest C.T. as screening tool
– CXR is not a sensitive way to screen for cancer
IVMS USMLE Step 1 Prep. 49

50. e-Medicine Articles
• Obstructive Airway Diseases
• Alpha1-Antitrypsin Deficiency
• Asthma
• Bronchiectasis
• Bronchiolitis
• Bronchitis
• Chronic Bronchitis
• Chronic Obstructive Pulmonary Disease
• Emphysema
• Status Asthmaticus
50IVMS USMLE Step 1 Prep.