Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9...
Transcript of Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9...
A. TeredesaiLSRO Meeting, Dec., 13, 2001
INBIFO/CRCSlide 1
Review of Histopathological Changes inthe Respiratory Tract of Rat Induced byInhalation of the Mainstream Smoke ofStandard Reference Cigarette 1R4F
LSRO Meeting Dec., 13, 2001 Slide 2 INBIFO/CRC12_2001.ppt
Outline
• Goal
• Anatomy and Histology
• Histotechnical Work
• Results– INBIFO
– Literature
LSRO Meeting Dec., 13, 2001 Slide 3 INBIFO/CRC12_2001.ppt
Goal
• Overview of the methods and procedures regardingthe histotechnical work and histopathologicalevaluation as well as an overview of thehistopathological changes following subchronicexposure to cigarette smoke
LSRO Meeting Dec., 13, 2001 Slide 4 INBIFO/CRC12_2001.ppt
Rationales
• Inhalation studies, special emphasis on thehistopathology of the target organs, i.e., respiratorytract organs
• Regulatory guidelines (OECD, EPA)
• Human relevance - association of tobacco smokeinhalation with laryngeal and bronchial cancers inhumans
LSRO Meeting Dec., 13, 2001 Slide 6 INBIFO/CRC12_2001.ppt
Nose
• Anatomy– vestibule
– cartilagenous septum that divides the nasal cavity into2 halves
– dorsal, middle, and ventral meatuses
– turbinates or conchae
• Histology– 3 basic epithelial types
– squamous epithelium
– respiratory epithelium
– olfactory epithelium
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Anatomy
• Larynx consists of 5 cartilages– epiglottis
– thyroid
– cricoid
– arytenoid
– u-shaped
LSRO Meeting Dec., 13, 2001 Slide 8 INBIFO/CRC12_2001.ppt
Histology
• 4 types of epithelium– squamous
– respiratory
– pseudostratified cuboidal
– squamoid
LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC12_2001.ppt
Trachea
• Anatomy– connects the larynx with the lungs
– 15 incomplete cartilaginous rings dorsally interconnected byligaments
– tracheal bifurcation at the level of 6th rib into a smaller leftand larger right extrapulmonary main bronchus
• Histology– pseudostratified respiratory epithelium
– ciliated cells
– serous cells
– mucous (goblet) cells
– basal cells
LSRO Meeting Dec., 13, 2001 Slide 10 INBIFO/CRC12_2001.ppt
Lung
• Left lung
• Right lung
2 lobes10 segmental bronchi
1 lobe12 to 13 segmental bronchi
3 lobes10 segmental bronchi
4 lobes14 to 15 segmental bronchifew subsegmental bronchi
Man Rat
LSRO Meeting Dec., 13, 2001 Slide 11 INBIFO/CRC12_2001.ppt
Cells of the Pulmonary Parenchyma
• Alveolar type I epithelial cells
• Alveolar type II epithelial cells
• Pulmonary endothelial cells
• Interstitial cells
• Macrophages
LSRO Meeting Dec., 13, 2001 Slide 12 INBIFO/CRC12_2001.ppt
Tissue Sectioning Method
• Sections at pre-established levels– nose: Young (1981)
– larynx: Lewis (1980)
– trachea: INBIFO
– lung: Lamb and Reid (1969)
• Purpose– adequate morphological evaluation
– uniform histological examination
– ensure correct comparison within and among studies
LSRO Meeting Dec., 13, 2001 Slide 13 INBIFO/CRC12_2001.ppt
Histopathological Evaluation
• Recording of findings in a consistent manner
• Use of standardized dictionary of criteria
• Consistent scoring system
• Evaluation in a blinded fashion, i.e., without theknowledge of treatment groups
LSRO Meeting Dec., 13, 2001 Slide 14 INBIFO/CRC12_2001.ppt
Results INBIFO
• Study reference– subchronic cigarette smoke inhalation studies
• Experimental condition– “nose only” mode
– TPM concentration range 40 to 200 µg TPM/l
– exposure duration: 6 h/d, 7 d/week for 21 or 90 days
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Histopathology
• Nose– respiratory epithelium (levels 1 and 2)
– reserve cell hyperplasia
– squamous metaplasia
– goblet cell hypertrophy/hyperplasia
– olfactory epithelium (levels 2, 3, and 4)– ulceration
– atrophy
– squamous metaplasia
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Nasal Septum, Level 1, Goblet CellHypertrophy/Hyperplasia
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Nasal Septum, Level 1, Goblet CellHypertrophy/Hyperplasia, AB-PAS Stain
LSRO Meeting Dec., 13, 2001 Slide 20 INBIFO/CRC12_2001.ppt
Dorsolateral Wall, Nose Level 1,Squamous Metaplasia
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Maxilloturbinate Tip, Nose Level 1,Normal
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Maxilloturbinate Tip, Nose Level 1,Hyperplasia
INBIFO/CRC CONFIDENTIAL
LSRO Meeting Dec., 13, 2001 Slide 23 INBIFO/CRC12_2001.ppt
Dorsomedial Region, Nose Level 2,Normal Olfactory Epithelium (low power)
LSRO Meeting Dec., 13, 2001 Slide 24 INBIFO/CRC12_2001.ppt
Dorsomedial Region, Nose Level 2,Normal Olfactory Epithelium (high power)
INBIFO/CRC CONFIDENTIAL