Introduction to pathology Flashcards
1
Q
Pathology superheros
A
Rudolf Virchow
Robert Hook
2
Q
Rudolf Virchow
A
- Pope of medicine
- Discredited the theory of the 4 humours
- All cells come from cells
3
Q
Robert Hooke
A
• Cell named after monks cells
4
Q
what is disease?
A
- 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
5
Q
Disease can be considered to be a consequence of
A
failed homeostasis
6
Q
what is pathology?
A
Pathos= suffering, logos= study
- Branch of medicine concerned with disease and understanding the process of disease
7
Q
pathology attempts to
A
- to explain why patients experience symptoms and guides treatment
- Involves diagnosis
8
Q
cellular pathology
A
- examine organs, tissues and cells for diagnosis and to guide treatment- often cancer work
9
Q
cellular pathology includes
A
histopatholgoy and cytopathology
10
Q
histopathology
A
core biopsies, cancer resection speciments, exised kin lesion and endoscopic biopsies
11
Q
cytology
A
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*
12
Q
cytopathology
A
13
Q
neuropathology
A
confided to brain, spinal cord, nerves and muscle
14
Q
forensic pathology
A
- medicolegal investigation of suspicious or criminal deaths, attend crime scenes, perform detailed autopsies and act as expert witnesses in court
15
Q
chemical pathology (clincial biochemistry)
A
Biochemical investigations of disease, e.g. endocrinology, diabetes, lipidology, thyroid disease, inborn errors of metabolism
16
Q
haemotology
A
Diseases of the blood (including leukaemias), blood clotting, blood transfusion and bone marrow transplantation
17
Q
immunology
A
Diseases of the immune system, e.g., allergy,
autoimmunity and immunodeficiency
18
Q
medical microbiology
A
Disease-causing microbes including advice on antibiotic usage
19
Q
importance of microscopic diangosis
A
- Definitive diagnosis
- Before major surgery to remove a lesion a microscopic diagnosis is required
- Guides the type and extent of surgery
20
Q
how do we arrive at a diagnosis
A
- Pattern recognition
- Histologist asks herself?
- Is this normal?
- Is this inflammatory or neoplasticism?
- Benign or malignant
- Is this primary or a metastasis?
21
Q
When its cancer, what else can histopathologists tell us?
A
- 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
22
Q
preparing a specimen: problems
A
- 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
23
Q
Problem 1: Autolysis
A
- Tissue autolysis (self-digestion) begins when blood supply is cut off
- Destroys cell and tissue architecture
24
Q
to prevent autolysis
A
fixation
- Hold tissue ‘suspended in animation ‘
- Formalin (formaldehyde in water)
- Penetration at approx 1mm/hr
- Usually fix for 24-48hours
25
role of fixatives
* Inactive tissue enzymes and denature proteins
* Prevent bacterial growth
* Harden tissue
26
**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
27
**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
28
**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
29
**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
30
**Problem 6: Colouring the tissue so it can be seen under a microscope**
Staining: usually with H&E
31
* Haemotoxylin
* stains nucleic acid purple
*
32
* Eosin
- stains protein and cytoplasm pink
33
34
**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
35
**Problem 8: Making a diagnosis**
Now the slides are ready to be looked at under a microscope by a pathologist
36
**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
37
**Immunohistochemistry**
Demonstrates substances in/on the cells by labelling them with specific antibodies
38
what enzyme is the antibody conjugated with which catalyses a colour producing reaction
peroxidase
- highlights the susbtances with a brown colour
39
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
40
**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
41
cytokeratins can give information about
primary site of carcinoma
42
**Molecular pathology**
Studies how diseases are caused by alterations in normal cellular molecular biology.
* Due to altered DNA, RNA or protein
43
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
44
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
