Intro to pathology Flashcards
What is disease?
Consequence of failed homeostasis
Gives morphological and functional disturbances
Lead to an identifiable group of symptoms and signs
What causes disease?
Intrinsic abnormalities
e.g. genetic mutations
External factors
e.g. microbial infection
What is pathology?
Study of disease and cellular dysfunction
What are the pathology disciplines?
Chemical pathology
study disturbances of metabolic processes
Haematology
study disturbances of cellular and coagulable components
Cellular pathology
Immunology
study of diseases of immune system
Microbiology
study of infectious diseases
What is cellular pathology?
The macroscopic and microscopic assessment of cells, tissues, organs
What is histopathology?
Looking at sections of tissue under a microscope
What are some examples of tissue sections looked at in histopathology?
Core biopsy
Cancer resection specimen
Excised skin lesion
What is cytopathology?
Cells are scraped off, sucked out
From lesion, organ, body fluid
Cells are disaggregated
Looked at under microscope
What are the advantages of histopathology?
Can assess cellular architecture
Can differentiate in situ from invasive disease
Can provide info on grade of tumour, stage of tumour, completeness of excision
Is therapeutic as well as diagnostic, because are removing lesion, cancerous cells etc.
What are the advantages of cytopathology?
Faster
Cheaper
Minimally invasive, safe
Can be used for cells in fluids
What are the disadvantages of cytopathology?
Higher inadequate errors
Error rates
What are some examples of specimens looked at in cytopathology?
Fine needle aspirates of breast, thyroid, lungs
Effusions
Sputum, urine
Cervical smears
What is neuropathology?
Cellular pathology
confined to brain, spinal cord, nerves, muscle
What is forensic pathology?
Medicolegal investigation of suspicious or criminal deaths
What are the uses of cytopathology?
Useful to confirm/exclude
cancer/dysplasia
before making other diagnoses
What is paediatric pathology?
Examine samples from children
What are the stages involved to prepare a slide in microscopy?
fixation cut up embedding blocking microtomy staining mounting
What is fixation?
Keep tissue in formalin solution
for 24-48 hours
What is the purpose of fixation?
To block tissue autolysis
by inactivating enzymes, denaturing proteins
Also to prevent bacterial growth
And to harden the tissue
Why does tissue autolysis occur?
Lack of blood supply to tissue
What does tissue autolysis result in?
Loss of cellular architecture
What is cutting up?
Tissue is cut up into small pieces put into a cassette has holes in the lid put into racks of formalin holes allow formalin to enter and bathe tissue
What is embedding?
Remove water from tissue using alcohol in a vaccuum
replace alcohol with xylene, because xylene mixes with wax
replace xylene with molten paraffin wax
will penetrate cells
What is the purpose of embedding?
To harden the tissue
so it can be cut into thin slices
What is blocking?
Take tissue out of casette put into metal block fill with paraffin wax body of cassette placed on top wax allowed to harden metal tray removed
What is microtomy?
Use microtome to cut thin sections from block
floated on water bath
picked up on microscope slide
What is the purpose of microtomy?
Cut tissue into thin sections
so can see through them with microscope
What is staining?
Use haematoxylin + eosin
haematoxylin stains nulcei purple
eosin stains cytoplasm and connective tissue pink
What is the purpose of staining?
To allow the tissue to be seen under the microscope
What is mounting?
Apply mounting medium to slide
put coverslip on top
mounting medium dries, hardens
attaching tissue to coverslip
What is the purpose of mounting?
To preserve and protect the tissue
preserved by hardening
protected by attaching to coverslip
What are the uses of microscopy?
To give a definite diagnosis
Show that surgery is required
guide the type and extent of surgery
To reason for alternative treatment, not surgery
e.g. chemotherapy, antibiotics, palliative care
May show that no treatment is required
How is histopathology used in cancer management?
Diagnosis of cancer Benign or malignant Primary or metastasis Grade of cancer Stage of cancer Involvement of margins Completeness of excision Efficacy of treatments
How does immunohistochemistry work?
Antigenic substance in or on cells
label it with antibodies
antibodies joined to an enzyme e.g peroxidase
catalyses a colour changing reaction
How does immunohistochemistry indicate the antigenic substance is present?
Colour change
Usually to a brown colour
What antigenic substances can be used in immunohistochemistry?
Actin
Cadherins
Hormone receptors e.g. oestrogen, progesterone
Her2 receptor
Micro-organisms e.g CMV, HPV, herpes simplex
Cytokeratins
What us the use of identifying actin?
To identify smooth muscle cells
What are cadherins?
Cell adhesion molcules
What is the use of identifying cadherins in cancer?
Deficient in some cancers e.g. lobular breast cancer
present in others
help to tell the type of cancer
What is the use of identifying oestrogen and progesterone hormone receptors in breast cancer?
Give idea of how patient will respond to specific treatments
What is the her2 receptor?
A growth factor receptor
What is the use of identifying her2 receptors in breast cancer?
If present in breast cancer
means will likely respond anti-her2 treatment
What is an example of an anti-her2 drug?
Herceptin
What are cytokeratins?
Intracellular
fibrous proteins
present in all epithelial cells
different types are present in different tissues
What is the use of identifying cytokeratins in cancer?
If present, means the cancer is epithelial in origin, in other words a carcinoma
CK7+ CK20- indicates lungs, thyroid, breast, endometrium, ovary
CK7- CK20+ indicates large bowel, some gastic carcinomas
What is molecular pathology?
Study of disease caused by altered DNA, RNA, proteins
What is meant by in situ molecular tests?
Looking for alterations in DNA in tissues prepared for microscopy
What is an example of an in situ molecular test?
FISH
What are the uses of FISH?
Can tell if a gene has been copied
deleted
translocated
if any viral genes are present
What is the use of FISH in breast cancer?
Looking at her2 gene
If there are extra copies of it
What is the significance of extra copies of the her2 gene in breast cancer cells?
Means are producing more growth factor
more affected by anti-her2 treatment e.g. herceptin
What is the use of DNA sequencing?
Show is a particular point mutation is present in a gene
What is the use of DNA sequencing in lung cancer?
Certain point mutations in EGFR gene
means cancer is likely to respond well to anti-EGFR treatment
What is an example of an anti-EGFR drug?
Erlotinib
What is the use mRNA expression profiling?
Gives an idea of how active genes area
What is the use of mRNA expression profiling with cancer?
Predicts behaviour of cancer
To do with spread
recurrence
When is a frozen section used?
Intra-operation Lesion identified Need to establish its nature e.g. inflammatory mass or neoplasm? Will affect the course of the surgery e.g. whether should resect it or not Have to be quick while patient is still under anasthetic
What is the process involved in using a frozen section?
Fresh tissue cut it into small pieces freeze it using a cryostat slice it thinly using microtome stain it mount it
What are the disadvantages of a frozen section?
May give incorrect diagnosis
false negative
Because cellular morphology is harder to interpret
Lesion of interest may not be in tissue submitted for frozen section
What information is included in the final report?
History
Macroscopic appearance
Micropscopic appearance
Conclusion
