Session 1 Flashcards
Define disease
Pathological condition of a body part, organ or system characterised by an identifiable group of signs or symptoms
What is pathology?
The study of suffering (disease and cellular dysfunction)
Cytopathology involves the study of…
Disaggregated cells rather than tissues to study disease
Histopathology involves the study of…
Tissues to study disease
Give examples of histologcal procedures (3)
Core biopsies
Cancer resection specimens
Excised skin lesions
Give examples of cytological procedures (2)
Fine needle aspirates of breast/thyroid/salivary glands
Cervical smears
Give 2 advantages of histological investigations/procedures over cytological investigations/procedures
Often therapeutic as well as diagnostic
Can assess architecture as well as cell atypia
Give 3 advantages of using cytological procedures/investigations over histological procedures/investigations
Faster and cheaper
Non-invasive or minimally invasive
Can be used for cells in fluid
The staging of cancer often follows the TNM system which looks at…
Tumour
Nodes
Metastases
What is autolysis? How can this affect microscopy of a tissue?
Self digestion of a tissue which occurs when the blood supply is cut off
Destroys cell and tissue architecture
How can autolysis be prevented?
By use of fixatives that inactivate tissue enzymes, prevent bacterial growth and harden the tissue
What chemical is typically used in fixation of sample for microscopy? What change in appearance will the tissue show after the fixative is applied?
Formalin
Raw meat —> Cooked meat
Tissues that have been fixed are placed into a ________ with holes in it to allow the chemical to penetrate the sample
Cassette
Why is it important for the tissue to be hard? What is this process called?
Allows the tissue to be cut into very thin slices
Embedding
What is commonly used as the hardening agent when a tissue is embedded?
Paraffin wax
Outline the process of embedding a tissue
Dehydration using alcohol in a vacuum
Alcohol replaced with xylene as it can mix with wax
Xylene replaced with molten paraffin wax
Tissues are typically cut to what thickness? Using which piece of equipment?
~3-4 microns
Microtome
What stain is most commonly used to stain samples?
H & E stain
Haematoxylin + Eosin
What does haematoxylin stain the most?
The nucleus most strongly blue
What does eosin stain the most?
The EM (cytoplasm and connective tissue) most strongly pink
What is the purpose of mounting a slice of tissue?
Preserves and protects the sample
What does immunohistochemistry involve?
Demonstrates substances in/on cells by labelling them with specific antibodies. These antibodies are usually linked to an enzyme that catalyses a colour-producing reaction.
What are cytokeratins? What is the clinical significance of these?
Family of intracellular fibrous proteins present in epithelial cells
They are markers for epithelial differentiation and show a tissue specific distribution in epithelia. So they can be used to show whether a cancer is a carcinoma and its primary site depending on the combination of different cytokeratins found
Why are frozen sections sometimes taken?
It’s a method of hardening tissue quickly - useful intra-operatively as it gives a quick result and can influence the course of the operation
Why are frozen sections not routinely used?
They provide a lower quality sample - cell morphology is not as good as in paraffin sections
What piece of equipment is used to take frozen sections?
A cryostat (microtome inside a freezer)
What is hypoxia?
Decreased oxygen supply to certain cells/tissues
What is ischaemia?
Decreased blood supply to certain cells/tissues
Why is ischaemia worse than hypoxia?
In ischaemia other nutrients such as glucose are also not supplied to cells/tissues
Name 4 types of hypoxia
Hypoxaemic hypoxia
Anaemia hypoxia
Ischaemic hypoxia
Histiocytic hypoxia
What is hypoxaemic hypoxia? Give an example of a cause
Where the arterial content of oxygen is low - e.g. There is reduced absorption of oxygen in the lungs
What is anaemic hypoxia? Give an example of a cause
Where there is decreased ability of haemoglobin to carry oxygen (e.g. In anaemia)
What is ischaemic hypoxia? Give an example of a cause
Where there is interruption to blood supply (e.g. There is blockage of a vessel)
What is histiocytic hypoxia? Give an example of a cause
The inability to utilise the oxygen within cells (e.g. Damaged oxidative phosphorylation enzymes due to cyanide poisoning)
The effects of hypoxia depends on…
Which cells/tissues it is affecting, some cells are damaged more quickly by hypoxia
E.g. Neurones last a few minutes, Fibroblasts last a few hours
What are hypersensitivity reactions?
Where the host tissue is injured secondary to an overly vigorous immune reaction
What are autoimmune reactions?
Immune system fails to distinguish self from non-self
What are free radicals?
Reactive oxygen species that have a single unpaired electron in its outer orbit making it unstable and more reactive
What are 3 significant free radicals? Which is the most dangerous?
OH* (hydroxyl)
O2- (superoxide)
H2O2 (hydrogen peroxide)
Hydroxyl
How are free radicals produced? (5)
Normal metabolic reactions - e.g. Oxidative phosphorylation
Inflammation - oxidative burst of neutrophils is used to kill microorganisms
Radiation - converts water to hydroxyl
Contact with unbound metals within the body (e.g. Fe/Cu)
Drugs (e.g. Metabolism of paracetamol in the liver)
Haemachromatosis is caused by…
Excess of iron
Wilson’s disease is caused by…
Excess of copper
What controls do we have against free radicals? (3)
Anti-oxidant system
Metal carrier and storage proteins
Enzymes that neutralise free radicals
What does the anti-oxidant system consist of? How does it work against free radicals?
Vitamins A, C & E
They donate electrons to the free radical
Give an example of a metal carrier protein that sequesters…
(I) iron
(II) copper
Transferrin
Ceruloplasmin
Give 3 examples of enzymes that neutralise free radicals.
Superoxide dismutase
Catalase
Glutathione peroxidase
How do free radicals injure cells?
They injure cell membranes and cause lipid peroxidation and then further free radicals
What is oxidative imbalance?
Where the number of free radicals overwhelms the anti-oxidant system
As well as lipids, which other cell structures can be oxidised by free radicals? What are the consequences of this?
Proteins, carbohydrates, DNA
Causes mutations in DNA and can therefore be carcinogenic, also bends proteins out of shape
What is the function of heat shock proteins?
During any cell injury, these proteins stop producing their usual products and aim to mend mis-folded proteins
What is karyolysis?
Nuclear fading - dissolution of chromatin due to action of DNAases and RNAases leading to cell death
What is pyknosis?
Nuclear shrinkage - DNA condenses into shrunken basophilic mass leading to cell death
What is karyorrhexis?
Nuclear fragmentation - nuclear membrane ruptures and nucleus undergoes fragmentation leading to cell death
How will injured cells appear under the microscope?
Often pale and swollen due to poorer function of the membrane