Introduction to pathology Flashcards
Pathology superheros
Rudolf Virchow
Robert Hook
Rudolf Virchow
- Pope of medicine
- Discredited the theory of the 4 humours
- All cells come from cells
Robert Hooke
• Cell named after monks cells
what is disease?
- Pathological condition of a body part, an organ or system characterise by an identifiable group of signs or symptoms
- Can be manifested in a single organ or whole person
Disease can be considered to be a consequence of
failed homeostasis
what is pathology?
Pathos= suffering, logos= study
- Branch of medicine concerned with disease and understanding the process of disease
pathology attempts to
- to explain why patients experience symptoms and guides treatment
- Involves diagnosis
cellular pathology
- examine organs, tissues and cells for diagnosis and to guide treatment- often cancer work
cellular pathology includes
histopatholgoy and cytopathology
histopathology
core biopsies, cancer resection speciments, exised kin lesion and endoscopic biopsies
cytology
Disaggregated cells ratehr than tissie
fine need aspirate of breast, thryoid, saliavry glands, lungs, effusions, cervical smears, sputum and urine
*faster, cheaper, safer and less invasive than histology*
cytopathology
neuropathology
confided to brain, spinal cord, nerves and muscle
forensic pathology
- medicolegal investigation of suspicious or criminal deaths, attend crime scenes, perform detailed autopsies and act as expert witnesses in court
chemical pathology (clincial biochemistry)
Biochemical investigations of disease, e.g. endocrinology, diabetes, lipidology, thyroid disease, inborn errors of metabolism
haemotology
Diseases of the blood (including leukaemias), blood clotting, blood transfusion and bone marrow transplantation
immunology
Diseases of the immune system, e.g., allergy,
autoimmunity and immunodeficiency
medical microbiology
Disease-causing microbes including advice on antibiotic usage
importance of microscopic diangosis
- Definitive diagnosis
- Before major surgery to remove a lesion a microscopic diagnosis is required
- Guides the type and extent of surgery
how do we arrive at a diagnosis
- Pattern recognition
- Histologist asks herself?
- Is this normal?
- Is this inflammatory or neoplasticism?
- Benign or malignant
- Is this primary or a metastasis?
When its cancer, what else can histopathologists tell us?
- Type of cancer
- Grade of cancer
- Stage of cancer
- Completeness of excision and if margins are involved, which ones
- Likely efficacy of further treatments (molecular pathology HER2, ER/PR, EGFR, PDL1 status)
- All of which influence decisions on further treatment and management
preparing a specimen: problems
- autolysis
- choosing the right bits fo tissue
- getting the tissue hard enough to be able to cut very thin slice
- getting the tissue into a peice of wax that can be cut
- cutting very thin section
- colouring the tissue so it can be seen under a microscope
- preservign and protecting the slice of tissue
Problem 1: Autolysis
- Tissue autolysis (self-digestion) begins when blood supply is cut off
- Destroys cell and tissue architecture
to prevent autolysis
fixation
- Hold tissue ‘suspended in animation ‘
- Formalin (formaldehyde in water)
- Penetration at approx 1mm/hr
- Usually fix for 24-48hours
role of fixatives
- Inactive tissue enzymes and denature proteins
- Prevent bacterial growth
- Harden tissue
Problem 2: Choosing the rights bits of tissue
- Usually the next day the specimen is examined and cut up by a pathologist
- Samples are taken and placed into a cassette
- Same size as stamp
- May need to take 30 or more
- Cassettes have holes in
- Placed in racks in formalin
Problem 3: Getting the tissue hard enough to be able to cut very thin slice
- Have to remove water first
- Dehydration using alcohol in a vacuum so water is drawn out of cells
- Then replace with alcohol with xylene which can mix with wax
- Operate overnight
Problem 4: Getting the tissue into a piece of wax that can be cut
- Tissue taken out of the cassettes by hand and put into metal blocks
- These are filled with molten paraffin wax and the body of the cassette is placed on top
- The wax is allowed to harden and the metal tray is removed
Problem 5: Cutting very thin sections
- Very thin(3-4microns) sections are cut from the block using a microtome
- Sections must be so thin that we can see through them with a microscope
Problem 6: Colouring the tissue so it can be seen under a microscope
Staining: usually with H&E
- Haemotoxylin
- stains nucleic acid purple
*
- Eosin
- stains protein and cytoplasm pink
Problem 7: Preserving and protecting the slice of tissue
Mounting: mounting medium is applied to the slide
- Coverslip is put on top
- Mounting medium dries and hardens, preserving the tissue and attaching the coverslip
Problem 8: Making a diagnosis
Now the slides are ready to be looked at under a microscope by a pathologist
Frozen section
- Used intraoperatively
- Method of hardening tissue quickly
- Not routinely used as morphology not as good as in paraffin sections
- Takes 10-15 minutes from receiving specimen in lab to giving a results
- Aim to establish presence and nature of lesion and influence the course of the operation
- 96% accuracy
Immunohistochemistry
Demonstrates substances in/on the cells by labelling them with specific antibodies
what enzyme is the antibody conjugated with which catalyses a colour producing reaction
peroxidase
- highlights the susbtances with a brown colour
which substances can be demonstrated by immunohistochemistry
Any substance that is antigenic can be demonstrated
- Contractile protein actin- identifies smooth muscle cells
- Cadherins (cell adhesion molecules)- deficient in some carcinomas
- Hormone receptors e.g. ER, PR
- HER2 receptors- growth factor receptor, predicts response of breast cancer to Herceptin
- Microorganisms e.g. HPV, Herpes simplex
Cytokeratins
- Family of intracellular fibrous proteins
- Present in almost all epithelia
- At least 20 known
- Markers for epithelial differentiation and show tissue-specific distribution in epithelia
cytokeratins can give information about
primary site of carcinoma
Molecular pathology
Studies how diseases are caused by alterations in normal cellular molecular biology.
- Due to altered DNA, RNA or protein
Molecular pathology: pathology due to altered DNA
-
In situ molecular tests show how DNA is altered in cells
- E.g. fluorescence in situ hybridisation (FISH) to test for gains of additional copies of Her2 gene in breast cancer
- Sequencing of DNA purified from tumour can show if mutation is present in a particular gene (e.g. if certain mutations in EGFR gene are present in lung cancer then the tumour is likely to respond to anti-EGFR treatments e.g. erlotinib
- Next generation sequencing enables many genes to be tested simultaneously for mutations
molecular pathology: mRNA expressing profiling methods demosntrate
mRNA expression profiling methods demonstrate the level of activity of a large number of genes simultaneously – microarray
- mRNA ‘signatures’ can predict how tumours are likely to behave
- e.g. the risk of breast cancer spread/ recurrence after surgery
