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

http://www.imhotepvirtualmedsch.com/

Marc Imhotep Cray, M.D. Professor Basic Medical Sciences

Chest X-ray of a person with advanced tuberculosis

IVMS USMLE Step 1 Prep.

Internet Pathology Laboratory for Medical Education

http://library.med.utah.edu/WebPath/webpath.html#MENU

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.

IVMS-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

IVMS USMLE Step 1 Prep.

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.

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

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.

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.

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 packyears 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

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

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.

Pneumonias

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
IVMS USMLE Step 1 Prep. 10

Pneumonias (2): Classification

Source: First Aid for the USMLE Step 1 2008, pg. 468

IVMS USMLE Step 1 Prep.

11

Pneumonias (3): Gross and histopathology

Lung, Lung, Lung, Lung, Lung, Lung, Lung, Lung, Lung, Lung, Lung, Lung, Lung, Lung, Lung, Lung, bronchopneumonia, gross [XRAY] bronchopneumonia, gross bronchopneumonia, gross lobar pneumonia, gross empyema, gross abscesses, gross abscesses, gross abscessing bronchopneumonia, gross bronchopneumonia, low power microscopic bronchopneumonina, high power microscopic bronchopneumnia, high power microscopic abscessing pneumonia, low power microscopic abscessing pneumonia, high power microscopic aspiration pneumonia, low power microscopic aspiration pneumonia, high power microscopic chronic abscess, gross

IVMS USMLE Step 1 Prep.

12

Pulmonary Tuberculosis
http://emedicine.medscape.com/article/230802-overview

Chandrasoma P, Taylor CR. Concise Pathology, 3rd ed. Stamford, CT: Appleton IVMS USMLE Step 1 Prep. & Lange, 1998: 523

13

Pulmonary Tuberculosis (2)

http://upload.wikimedia.org/wikipedia/commons/2/2f/Tuberculosis_symptoms.svg

IVMS USMLE Step 1 Prep.

14

Pulmonary Tuberculosis (3)

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

mmons/0/0a/TB_Culture.jpg

15

Pulmonary TB (4)
Diagnosis: confirmed by CXR, PPD, sputum smears and culture

Mycobacterium tuberculosis Ziehl-Neelsen stain

Treatment: 4 drug therapy

See Tuberculosis Treatment & Management http://emedicine.medscape.com/article/230802treatment

Chest X-ray of a person with advanced tuberculosis http://upload.wikimedia.org/wikipedia/commons/9/9c/Tub erculosis-x-ray-1.jpg 16

IVMS USMLE Step 1 Prep.

Obstructive Lung Disease General

Obstruction of air flow through airways Major causes:
asthma bronchiectasis, emphysema and bronchitis (COPD)
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.

IVMS USMLE Step 1 Prep.

17

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

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

Bronchitis vs Emphysema

Source: First Aid for the USMLE Step 1 2008,pg 400

IVMS USMLE Step 1 Prep.

20

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

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

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

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

COPD: Clubbing

IVMS USMLE Step 1 Prep.

25

COPD: Hyperinflation

IVMS USMLE Step 1 Prep.

26

COPD flattened diaphragms, lucency

IVMS USMLE Step 1 Prep.

27

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

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

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
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
30

IVMS USMLE Step 1 Prep.

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

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

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

Restrictive lung disease

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 effortpolio, myasthenia gravis b. Poor structural apparatusscoliosis, 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 miners silicosis, asbestosis) d. Sarcoidosis e. Idiopathic pulmonary fibrosis (repeated cycles of lung injury and wound healing with collagen) f. Goodpastures syndrome g. Wegeners granulomatosis h. Eosinophilic granuloma (histiocytosis X) i. Drug toxicity (bleomycin, busulfan, amiodarone)
IVMS USMLE Step 1 Prep. 34

Cystic Fibrosis

Cystic fibrosis
IVMS USMLE Step 1 Prep. 35

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

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

http://en.wikipedia.org/wiki/File:Cystic_Fibrosis_Respiratory_Infections_by_Age.svg

37

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

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

Cystic Fibrosis(6)
Treatment;
Aggressive airway hygiene Nutritional support including pancreatic enzyme replacement Antibiotics Bronchodilators

IVMS USMLE Step 1 Prep.

40

Lung Cancer

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
IVMS USMLE Step 1 Prep. 41

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

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

Lung Cancer: Types (2)

Source: First Aid for the USMLE Step 1 2008, pg. 443
IVMS USMLE Step 1 Prep. 44

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

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

Lung Cancer: Evaluation

History and physical examination CXR/CT scan No lab is helpful Bronchoscopy VATS

IVMS USMLE Step 1 Prep.

47

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

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

e-Medicine Articles
Obstructive Airway Diseases Alpha1-Antitrypsin Deficiency Asthma Bronchiectasis Bronchiolitis Bronchitis Chronic Bronchitis Chronic Obstructive Pulmonary Disease Emphysema Status Asthmaticus

IVMS USMLE Step 1 Prep.

50

IVMS is the ultimate medical student Web 2.0 companion. It is horizontally and vertically integrated SDL-Face to Face hybrid courseware designed, developed and curated by Marc Imhotep Cray, M.D. The courseware is essentially a digitally tagged and content enhanced replication of the United States Medical Licensing Examination's Cognitive Learning Objectives (Steps 1, 2 or 3), Including comprehensive hypermedia BMS and Clinical Medicine didactic learning outcomes, detailed content enriched learning objectives, authoritative reusable learning object (RLO) integration scholarly Web Interactive PowerPoint-driven multimedia shows / PDFs, rapid review and high yield tools, USMLE-Type Mock exams, e-textbooks and more.
IVMS Premium Services: Individualized Webcam facilitated USMLE Step 1 Tutorials with Dr. Cray Starting at $50.00/hr., depending on pre-assessment. 1 BMS Unit is 4 hr. General Principles and some Organ Systems require multiple units to complete in preparation for the USMLE Step 1. A HIGH YIELD FOCUS in Biochemistry / Cell Biology, Microbiology / Immunology, the 4 Ps-Physiology, Pathophysiology, Pathology and Pharmacology and Introduction to Clinical Medicine is offered. Webcam Facilitated USMLE Step 2 Clinical Knowledge and Clinical Skills didactic tutorials starting at $60.00 per hour /1 Unit is 4 hours, individualized one-on-one and group sessions, Including Introduction to Clinical Medicine and all Internal Medicine sub-specialties at the clerkship level. All e-books and learning tools are provided. Contact Dr. Cray today for a FREE Demo Session. drcray@imhotepvirtualmedsch.com 51