Post on 04-Apr-2020
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
LSRO Meeting Dec., 13, 2001 Slide 7 INBIFO/CRC12_2001.ppt
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
LSRO Meeting Dec., 13, 2001 Slide 15 INBIFO/CRC12_2001.ppt
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
LSRO Meeting Dec., 13, 2001 Slide 17 INBIFO/CRC12_2001.ppt
Nasal Septum, Level 1, Goblet CellHypertrophy/Hyperplasia
LSRO Meeting Dec., 13, 2001 Slide 18 INBIFO/CRC12_2001.ppt
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
LSRO Meeting Dec., 13, 2001 Slide 21 INBIFO/CRC12_2001.ppt
Maxilloturbinate Tip, Nose Level 1,Normal
LSRO Meeting Dec., 13, 2001 Slide 22 INBIFO/CRC12_2001.ppt
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