Principles and techniques of pathology Flashcards
What is general pathology?
- reactions of cells and tissues to abnormal stimuli and inherited defects
What is systemic pathology?
- specific disease processes as they affect organs and systems
What are the 4 components of pathology?
- aetiology
- pathogenesis
- molecular and morphological changes
- functional derangements and clinical manifestations
What is the definition of aetiology?
- the cause of a disease
What are the two classes of aetiology?
- genetic
- acquired
- may be a combination
What is genetic aetiology?
- inherited mutations, disease associated gene variants
What is acquired aetiology?
- infectious, nutritional, chemical and physical
What is pathogenesis?
- the sequence of events in the response of cells and tissues to the aetiologic agent
- from initial stimulus to the ultimate expression of the disease
What do therapeutic interventions often focus on?
- focus on specific pathways within the pathogenesis of a disease
What is pathophysiology?
- the specific changes in physiology
What are molecular changes?
- changes in the molecular and or immunological expression in diseases states
What are morphological changes?
- structural changes in cells, tissues or organs
- may be characteristic of a disease or diagnostic
INFO CARD:
- in recent years additional attention had been given to microbiological changes in disease states - microbiome
What are functional derangements?
- end result of genetic, biochemical and structural changes in cells and tissues
What is clinical manifestations (signs) and disease progress?
- the result of functional abnormalities
INFO CARD:
- Rudolf Virchow proposed that disease starts with the alteration of cells, which we now recognise to be structural and/or functional alteration
What does cell injury disrupt?
- disrupts homeostasis
The aetiologies of cell injury are numerous but they lead to 4 basic mechanisms - what are these?
- ATP depletion (disrupts processes that require energy)
- cell membranes of increased permeability
- disruption of biochemical pathways
- DNA damage (so cant coordinate things)
- there may be one or a combination of these
The injured cell can react in a limited number of ways - what are these?
- adaptation
- degeneration
- death
- may do all of these sequentially
What is often the ultimate cause of cell injury?
- oxygen deficiency
What are the mechanisms that can lead to oxygen deficiency and ultimately cell injury?
- inadequate oxygen of blood e.g., cardiac or respiratory failure
- reduced vascular perfusion (ischaemia)
- reduced oxygen transport e.g., anaemia and CO exposure
- inhibition of respiratory enzymes in the cell e.g., cyanide
What are the physical agents that can cause cell injury?
- trauma
- temperature extremes
- ionising radiation
- electric shock
What are the infectious agents that can cause cell injury?
- prions
- viruses
- bacteria
- fungi
- parasites
What nutritional imbalances can cause cell injury?
- dietary deficiencies
- long term starvation
- caloric excess
- dietary toxicities
What are the genetic or developmental derangements that can cause cell injury?
- inherited diseases
- metabolic diseases
- neoplasia
- autoimmune diseases
- susceptibility to infection
- congenital abnormalities
Workload imbalance can cause cell injury - what happens if there is increased workload?
- respond by hypertrophy or hyperplasia (cell dependent)
- if excessive = leads to cell degeneration and death
Workload imbalance can cause cell injury - what happens if there is reduced workload?
- loss of innervation, hormones or growth factors
- leads to atrophy
- excessive cells can be removed by apoptosis
Chemicals, drugs and toxins can also cause cell injury - what can these compounds do?
- alter homeostasis
What does toxicity depend on in cells?
- depends on cell tolerance to the effect of the compound
What does a cells susceptibility to chemicals, drugs and toxins depend on?
- miotic rate
What is miotic rate?
- The ability to:
- take-up
- bind
- Concentrate
- Metabolise
Cell injury can also be caused by immunological dysfunction - what are examples of this?
- failure to respond (immunodeficiency)
- overreaction (allergic/hypersensitivity reaction)
- reaction to self (autoimmunity)
Aging an cause cell injury through accumulated damage to cells through what?
- proteins
- lipids
- nucleic acids
- depends on the ability of different cells to replicate or repair
What are the categories of aetiology?
* think VITAMINCDE
V- Vascular
I - inflammatory/infectious
T- trauma/toxicity
A - autoimmune
M - metabolic
I - iatrogenic/idiopathic
N - nutritional/neoplastic
C- congenital
D - degenerative
E - endocrine
What is ante mortem sampling?
- samples from the living
What do clinical pathologists use for ante mortem sampling?
- biochemistry
- cytology
- haematology
- analysis of other body fluids (urinalysis and CSF analysis)
What do anatomical pathologists do?
- use surgical biopsies for histopathology
What is histopathology and what does it identify?
- the microscopic examination of tissues
- identification of morphological changes in anatomy
What is the advantage of histopathology over cytology?
- interpretation of changes in tissue architecture and relationship between cells and tissues
What does histopathology require?
- requires fixed ( most often 10% neutral buffered formalin) tissue
What stain is routinely used in histopathology?
- uses haematoxylin and eosin staining
Many histochemical stains exit to do what?
- characterise features seen (pigments, microorganism)
- reveal features not visible on H&E
- differentiate structures and tissue components
- react with chemical components of tissues
Formalin fixed paraffin embedded tissue blocks can be archived and used for comparison later - such as?
- samples from the same animal (clinical progression)
- control tissues (for special stains)
- research
What is immunohistochemistry?
- an antibody labelling technique, made visible using a chromogen or fluorescent reporter
Immunohistochemistry relies on epitopes - what are these?
- areas of proteins in the target to bind specific antibodies
What can immunohistochemistry be used to identify?
- cell types
- tissue/protein components
- microorganisms
What are the antibodies like in immunohistochemistry?
- specific to the target (e.g., an antibody raised against a specific microorganism or unique feature of a cell type/tissue component)
- identify of the target is based in the combination of antibodies that can or cannot label it
What techniques can be used for assessing samples obtained from clinical cases/and or PME?
- Histopathology
- Immunohistochemistry
- Microbiology / parasitology
- Molecular techniques
- Ultrastructural pathology (less common
What samples can be analysed for microbiologists and parasitologists?
- Samples (e.g. swabs, faeces) taken in clinical practice, or at post mortem examination
What information can be provided from samples sent to microbiologists and parasitologists?
- Provides specialist information about presence of organisms
- Can provide additional information for treatment (e.g. antibiotic sensitivity)
What does ultrastructural pathology use?
- Uses electron microscopy to examine cellular and subcellular morphological changes
Why is untrastrucural pathology limited?
- due to cost, specialist sample processing and availability of facilities with EM expertise and infrastructure
The target area for ultrastructural pathology is very small so how should it be used?
- needs to be used carefully and with other information about the
disease process
Where is ultrastructural pathology used?
- in research more than clinical settings
Where may ultrastructural pathology be used in a clinical setting?
- Specialist renal pathology
What are molecular techniques for PME?
- ELISA
- PCR
What is ELISA?
- Another immunological technique used on fluid samples (e.g. plasma, serum, urine)
What can ELISA be used to quantify?
- Can be used to quantify levels of a protein in a sample (e.g. inflammatory mediators, protein
component of a microorganism)
What is ISH?
- In situ hybridization
What targets are used in ISH?
- Whilst IHC needs a protein target, ISH techniques have a nucleic acid
target (mRNA)
How is ISH performed?
- A probe (a complimentary strand of DNA or RNA) is used to bind to the
target - An antibody, bound to an enzyme, is used to label the sites of probe
binding - A substrate is added, and reacts at the site of the enzyme, to produce a
product which can be visualised - Fluorescent and chromogens are used
- Allows assessment of expression of genes, or microbial genetic material
(e.g. locating viral material)
