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Pathological Processes > Introduction > Flashcards

Introduction Flashcards

1
Q

What is chemical pathology?

A 
Chemical Pathology (Clinical Biochemistry)
– Biochemical investigations of disease, e.g., endocrinology, diabetes, lipidology, thyroid disease inborn errors of metabolism
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2
Q

Which diseases are investigated in haematology?

A

Diseases of the blood (including leukaemias), blood clotting, blood transfusion and bone marrow transplantation

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3
Q

Which diseases are investigated in immunology?

A

Diseases of the immune system, e.g., allergy, autoimmunity and immunodeficiency

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4
Q

What does medical microbiology investigate?

A

Disease-causing microbes including advice on antibiotic usage. They are also responsible for infection control.

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5
Q

What do cellular pathologists do?

A

– Examine organs, tissues and cells for diagnosis and to guide treatment, often cancer work
– Conduct autopsies

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6
Q

What is cytopathology?

A

Disaggregated cells rather than tissue

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7
Q

What is neuropathology?

A

confined to brain, spinal cord, nerves and

muscle

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8
Q

Forensic pathology

A

medicolegal investigation of suspicious or
criminal deaths, attend crime scenes, perform detailed autopsies
and act as expert witnesses in court

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9
Q

Paediatric pathology

A

tissue samples from children, undertake

foetal, perinatal and paediatric autopsies

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10
Q

What is the importance of a microscopic diagnosis?

A
  • Definitive diagnosis e.g. Don’t want to remove breast if a lump isn’t cancer
  • Before major surgery to remove a lesion a microscopic diagnosis is required
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11
Q

Give an example of a procedure used in histology

A

Core biopsies, cancer resection specimens, excised skin lesions, endoscopic biopsies

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12
Q

Give an example of a procedure used in cytology

A

Fine needle aspirates of breast, thyroid, salivary glands, lung; effusions, cervical smears; sputum; urine

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13
Q

Describe the key features of histology

A
  • Often therapeutic as well as diagnostic
  • Can assess architecture as well as cellular atypia
  • Can differentiate invasive from in situ disease
  • Can provide information on completeness of excision and more complete information on grading and staging
  • Better for immunohistochemical and molecular testing
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14
Q

Describe the key features of cytology

A
  • Faster and cheaper that histology
  • Non-invasive or minimally invasive and safe
  • Can be used for cells in fluids
  • Sometimes a preliminary test before other investigations or more tissue taken for histology
  • Higher inadequate and error rates
  • Generally used to confirm/exclude cancer/dysplasia and not to diagnose any other condition
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15
Q

How does a histopathologist arrive at a diagnosis?

A 
• Pattern recognition 
• This histopathologist asks herself:
– Is this normal or not?
– Is this inflammatory or neoplastic?
– Is this benign or malignant?
– Is this a primary tumour or a metastasis?
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16
Q

What can a histopathologist determine about a cancerous sample?

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
17
Q

How do pathologists use a sample?

A

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

18
Q

What is autolysis?

A

• 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

19
Q

How do you prevent autolysis?

A

Fixatives:
– Inactivate tissue enzymes and denature proteins
– Prevent bacterial growth
– Harden tissue (to be able to cut cells)
- Usually formalin

20
Q

Describe the process of fixation

A
  • Hold tissue in ‘suspended animation’
  • Use formalin
  • Fix for 24-48 hours
21
Q

How do pathologists chose the right bit of a tissue?

A

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 (to allow chemicals in)
– They are placed in racks in formalin

22
Q

How do pathologists get the tissue hard?

A

• In order to be able to cut very thin sections the
tissue has to be surrounded and impregnated with a hardening agent
• Usually paraffin wax
• 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
- Use processors to embed tissue overnight

23
Q

How to pathologists get the tissue into a piece of wax that can be cut?

A
  • 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
24
Q

How do you cut very thin sections?

A 
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
25
Q

How are wax sections from a microtome put onto microscope slides?

A

The thin wax sections are floated on a water-bath and picked up on a microscope slide

26
Q

Which stains are usually used in pathology?

A

Staining - usually with H&E:
– Haematoxylin stains nuclei purple (From the bloodwood tree)
– Eosin stains cytoplasm and connective tissue pink
– Other stains can be used to demonstrate different substances/structures/micro-organisms

27
Q

How are tissues preserved and protected/

A

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

28
Q

What is immunohistochemistry?

A

• Demonstrates substances in/on cells by
labelling them with specific antibodies
• 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

29
Q

What are cytokeratins? How can this be used in pathology?

A

– Family of intracellular fibrous proteins
– Present in almost all epithelia
- Used frequently in immunohistochemistry
– Markers for epithelial differentiation and show tissue-specific distribution in epithelia (is it epithelial in origin e.g. Carcinoma)
– 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

30
Q

What is molecular pathology?

A

• Studies how diseases are caused by alterations in normal cellular molecular biology
• Can be due to altered DNA, RNA or protein
• In situ molecular tests show how DNA is altered in tissues prepared for microscopy
– E.g., fluorescence in situ hybridisation (FISH) to test for gains of additional copies of Her2 gene in breast cancer

31
Q

What substances can be tested for using immunohistochemistry?

A

– 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

32
Q

How do pathologists use DNA sequencing?

A

• Sequencing of DNA purified from tumour
tissue can show if a 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

33
Q

What are mRNA expression profile methods used for?

A
  • mRNA expression profiling methods demonstrate the level of activity of a large number of genes simultaneously
  • mRNA
34
Q

What are frozen sections used for?

A
  • Urgent histopathology
  • Method of hardening tissue quickly
  • Morphology not as good in paraffin sections
  • Used mid operation to decide best course of action
  • Takes about ten minutes
  • Low accuracy

Pathological Processes (13 decks)

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