Intro To Pathology Flashcards
What is disease
A pathological condition of a body part, an organ, or a system characterised by an identifiable group of signs or symptoms
Disease can be considered to be a consequence of failed homeostasis with consequent morphological and function disturbances
These disturbances can be manifest at the level of the whole person, an organ, or a tissue. However, in all physical diseases, the cell is the central player.
What is pathology
Study of suffering (pathos = suffering, logos = study)
Branch of medicine concerned with disease and understanding the process of disease
– Biology = study of life and cellular function
– Pathology = study of disease and cellular dysfunction
Attempts to explain why patients experience symptoms and guides treatment
Pathology disciplines
Chemical Pathology (Clinical Biochemistry)
Biochemical investigations of disease, e.g. endocrinology, diabetes, lipidology, thyroid disease, inborn errors of metabolism
Haematology – 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
Cellular Pathology (Histopathology and Cytopathology)
Examine organs, tissues and cells for diagnosis and to guide treatment, often cancer work
Conduct autopsies
Cytopathology – disaggregated cells rather than tissue
Neuropathology – confined 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
Paediatric Pathology – tissue samples from children, undertake foetal, perinatal and paediatric autopsies
Histology vs Cytology
Histology - examples - core biopsies, cancer resection specimens, excised skin lesion and endoscopic biopsy
Comments - often therapeutic as well as diagnostic - can assess architecture and see if there are any atypical cells - can differentiate between invasive and in situ disease - get provide better information on grading and staging of cancer - better for immunohistochemical and molecular testing
Cytology - fine needle aspirates of breast, thyroid, salivary glands, lungs, effusions and cervical smears
Comments - faster and cheaper, minimally invasive and safe, can be used for cells in fluids, can be done as a preliminary test before further tests done
When its cancer what can the histopathologists tell us
When looking at type of cancer and how far gone it is
Type of cancer e.g. enlarged lymph node in the neck
Grade of cancer - Breast
Stage of cancer - 3 things to look at - stage of tumour, stage of nodes and stage of metastases (TNM)
Completeness of excision and if margins are involved which ones
Likely efficacy of further treatments
All of which influence decisions on further treatment and magnement
Cancer is graded/ put into stages:
For Stage of tumor its 0 to 3 with 0 being no tumor to 3 being tumour has crossed the basement membrane
For stage of nodes its 0 to2 with 0 being nothing present on nodes to 2 being cancer present on local and distant nodes
For metastasis it 0 to 2 with 0 being no metastasis
Problems with this cancer grading method
Need to ensure completeness of excision - otherwise if some is left behind, then it is likely to grow back
Component of subjectivity - some tumours are very hard to distinguish between benign and malignant - this diagnosis is key thought as it determines action that needs to be taken -
Things can look very similar - so there is plenty of overlap - no everything is black and white
Diagnosing cancers
In order to do what we do we need to look at the tissue under a microscope
Take slices from the tissue so thin we can see through them with a microscope
Colour the tissue so we can see it under a microscope
Problem 1 with this autolysis
Tissue autolysis (self-digestion) begins when the blood supply is cut off
It destroys cells and tissue architecture – Everything we need to make a diagnosis - therefore we need to prevent this process occurring so that we can analyse the tissue SO:
We can block the biochemical process of autolysis with fixatives
Fixatives: – these inactivate the tissue’s enzymes and denature proteins – which Prevent bacterial growth – and Hardens tissue
Fixation - Now Hold the harden tissue in ‘suspended animation’
Usually use formalin (formaldehyde in water)
Penetrates tissue at approximately 1mm/hr
Usually fix for 24-48 hours
Problem 2 - choosing the right bits of tissue
Usually next day the specimen is examined and cut-up by a pathologist
Samples are taken and placed into a cassette
About the size of a stamp so they can be adequately infiltrated by chemicals
May need to take 30 or more in complicated cases
Cassettes have holes in
They are placed in racks in formalin
Problem 3 - getting the tissue hard enough to be able to take very thin slices
In order to be able to cut very thin sections the tissue has to be surrounded and impregnated
with a hardening agent so we usually use paraffin wax - usually done overnight
Have to remove the water from the tissue first:
– Dehydration using alcohol in a vacuum so that water is drawn out of the cells
– Then replace alcohol with xylene which can mix with wax
– Then replaced xylene with molten paraffin wax, which will even be inside the cells
Problem 4 - getting 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 slices
Very thin (3-4 microns) sections are cut from the block using a microtome
Sections must be so thin that we can see through them with a microscope
The thin wax sections are gloated on a water bath and picked up on a microscope slide
Problem 6 - colouring the tissue so it can be seen under a microscope
Staining - usually with H&E: – Haematoxylin stains nuclei purple
From the bloodwood tree (Greek: haima = blood; xylon = wood)
Eosin stains cytoplasm and connective tissue pink
Other stains can be used to demonstrate different substances/structures/micro-organisms
Problem 7 - preserving and protecting the slices 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
Slides are now ready to be looked at under a microscope by a pathologist
Immunohistochemistry - the use of antibodies
Demonstrates substances in/on cells by labelling them with specific antibodies
First used in 1941
Usually the antibody is joined to an enzyme (e.g., peroxidase) that catalyses a colour- producing reaction
Highlights the substances usually with a brown colour
Any substance that is antigenic can be demonstrated -
e.g. - Contractile protein actin – identifies smooth muscle cells
— Cadherins – cell adhesion molecules, deficient in some carcinomas, e.g., lobular breast carcinoma
— Hormone receptors, e.g., ER, PR
— Her2 receptor – growth factor receptor, predicts response of breast cancer to Herceptin
— Microorganisms, e.g., CMV, HPV, herpes simplex
Cytokeratins - Family of intracellular fibrous proteins and present in almost all epithelia
At least 20 known
Markers for epithelial differentiation and show tissue-specific distribution in epithelia
Can give information about the primary site of a carcinoma, particularly when used in combination:
CK7+/CK20- : lung, breast, endometrium, ovary, thyroid
CK7-/CK20+ : large bowel, some gastric carcinomas
