Session 1 Flashcards
(83 cards)
1
Q
What is a disease?
A
A pathological condition of a body part, an organ or a system characterised by an identifiable group of signs or symptoms
2
Q
What is the difference between sign and symptom?
A
Sign = objective Symptom = observed by patient
3
Q
Disease can be considered to be what?
A
Consequence of failed homeostasis with consequent morphological and functional disturbances (tissue, organ or whole person level)
4
Q
What is pathology?
A
Study of sufferinng - disease and unferstand the process of disease - explain why patients experience symptoms and guides treatment - can involve diagnosis
5
Q
Describe the different branches of pathology?
A
Chemical pathology Haematology Cellular pathology (histopathology and cytology) - Neuropathology, Forensic pathology, Paediatric pathology Immunology Medical microbiology - Virology
6
Q
What is chemical pathology?
A
Clinical biochemistry
Biochemical investigations - endocrinology, diabetes, lipidology, thyroid disease, inborn errors of metabolism
7
Q
What is haematology?
A
Diseases of blood (leukaemias), blood clotting, blood transfusion and bone marrow transplantation
8
Q
What is cellular pathology?
A
Examine organs, tissues and cells for diagnosis and treatment and autopsies
9
Q
What does neuropathology include examination of?
A
Brain, spinal cord, nerves and muscle
10
Q
What is forensic pathology?
A
Medicolegal investigation of suspicious or criminal deaths
11
Q
What is paediatric pathology?
A
Children - samples/autopsies
Foetal/Perinatal/Paediatric
12
Q
What is immunology?
A
Diseases of the immune system - allergy, autoimmunity and immunodeficiency
13
Q
What is virology?
A
Study of infectious diseases - antibiotics
14
Q
What is microscopic diagnosis?
A
Definitive diagnosis
e.g. between fat necrosis and cancer
Important before major surgeries to remove lesions
15
Q
What is the difference between histology and cytology?
A
Histology - core biopsies, cancer resection specimens, excised skin lesions, endoscopic biopsies
Cytology (disaggregated cells) - fine needle aspirates of breast, thyroid, salivary glands, lungs, effusions. cervical smears, sputum or urine
16
Q
What are the advantages of histology?
A
- can be therapeutic and diagnostic
- can assess architecture and cellular atypia
- info on completeness of excision / staging and grading
- better for immunohistochemistry and molecular testing
17
Q
What are the advantages of cytology?
A
- faster and cleaner
- non/minimally invasive and safe
- cells in fluids
- preliminary test before other investigations
- higher inadequate and error rates
- confirms/discludes cancer/dysplasia - not used for many other diagnoses
18
Q
How can pattern recognition help you to reach a diagnosis?
A
Normal or not?
Inflammatory or neoplastic (growth)?
Benign or malignant?
Primary tumour or metastasis?
19
Q
What do you need to consider when cancer is a possible diagnosis?
A
Influences decisions on further treatment and management
- type of cancer
- stage of cancer - metastasis?
- grade of cancer - how different is it?
- completeness of excision and if margins are involved - which ones?
- likely efficacy of further treatments -> ER/Her2 receptors - oestrogen receptor
20
Q
What are the different stages of obtaining a report from a pathological specimen?
A
Fixation Cut-up (trimming) Embedding (processing) Blocking Microtomy Staining Mounting Microscopy
21
Q
What is fixation?
A
Tissue autolysis begins when blood supply is cut off
Block this by process of fixation - inactivate enzymes and denature proteins - prevents bacterial growth and hardens tissue
Can use FORMALIN
22
Q
What is trimming or cutting up?
A
Specimen is examined and cut up
Samples are taken and placed in a cassette - placed in racks of formalin
23
Q
What is embedding or processing?
A
Need to remove water and add paraffin wax to allow samples to be cut very thinly
24
Q
What is blocking?
A
Tissue is put into a metal tray and paraffin wax is allowed to set
25
What is microtomy?
Very thin setions are made - using a microtome
| Can see through the sections
26
What is staining?
Usually with H&E
H = nuclei are purple
E = cytoplasm and CT are pink
27
What is mounting?
Mounting medium applied to slide - coverslip on top - preserves tissue
28
What is microscopy?
Ready to be looked at by a pathologist
29
What is immunohistochemistry?
- demonstrates substancees in/on cells by labelling them with specific antibodies
- antibody joined to an enzyme that catalyses a colour change
30
What substances can be used for immunohistochemistry?
Any antigenic substances can be demonstrated:
- contractile protein actin - identifies SMCs
- cadherins - cell adhesoon molecules, deficient in some carcinomas
- hormone receptors e.g. ER/PR
- Her2 receptor - growth factor receptor, predicts response of cancer to Herceptin
- microorganisms e.g. CMV, HPV, Herpes Simplex
- cytokeratins - present in almost all epithelia - intracellular fibrous proteins - shows tissue specific distribution and can be used in combination
31
What is molecular pathology?
Studies how diseases are caused by alterations in normal cellular molecular biology - due to DNA, RNA or proteins being altered
32
What are the different ways altered DNA, RNA or proteins can be seen?
FISH - e.g. copies of Her2 gene in breast cancer
Sequencing DNA from cancer tissue - see if there is a mutation on a specific gene
mRNA expression profiling - level of activity in different genes can be detected
33
What are frozen sections?
Method of hardening tissue quickly - can be done quickly during an operation to establish presence and nature of a lesion
34
What are the different sections seen in a histology report?
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Clinical history
Macroscopic
Microscopic
Conclusion
Reported by:
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35
All cells have effective mechanisms to deal with wild changes in?
Environmental conditions
36
More severe changes in environment leads to?
cell adaptation
cell injury
cell death
37
What does the degree of injury depend on?
- type
- severity
- type of tissue
38
What are the causes of cell death?
Hypoxia
Toxins
Physical agents - direct trauma, extremes in temperature, changes in pressure, electric currents
Radiation
Microorganisms
Immune mechanisms
Dietary insufficiency and deficiencies, dietary excess
39
What is hypoxia?
Hypoxia is not the same as ischaemia
Hypoxia = not enough O2
Ischaemia = reduced blood supply
40
What are the causes of hypoxia?
Hypoxaemic hypoxia
Anaemic hypoxia
Ischaemic hypoxia
Histiocytic hypoxia
41
What is hypoxaemic hypoxia?
Arterial content of O2 is low - reduced absorption secondary to lung disease
42
What is anaemic hypoxia?
Decreased ability of haemoglobin to carry oxygen - anaemia/CO poisoning
43
What is ischaemic hypoxia?
Interruption to blood supply - caused by blockage of a vessel or heart failure
44
What is histiocytic hypoxia?
Inability to utilise oxygen in cells due to disabled oxidative phosphorylation enzymes - cyanide poisoning
45
How can the immune system damage the body's own cells?
Hypersensitivity reactions - host tissue is injured secondary to an overly vigorous immune reaction e.g. urticaria (hives)
Autoimmune reactions - immune system fails to distinguish self from non-self e.g. Grave's disease of the thyroid
46
What are the cell components susceptible to injury?
Cell membranes - plasma membrane/ organellar membranes
Nucleus - DNA
Proteins - structural (enzymes)
Mitochondria - oxidative phosphorylation
47
What happens at a molecular level in hypoxia?
reversible injury -> ischaemia -> mitochondria (less OP) -> less ATP made ->
Increase in glycolysis -> decrease in pH and glycogen -> clumping of nuclear chromatin
Decrease in Na+ pump -> more Ca2+, H20, Na+ and less K+ -> cellular swelling, loss of microvilli, blebs, ER swelling and myelin figures
Detachment of ribosomes -> less protein synthesis -> lipid deposition
48
What occurs during prolonged hypoxia?
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Increase in Ca2+
ATPase - decreased ATP
Phospholipase - decreased phospholipids
Protease - disruption of membrane and cytoskeletal proteins
Endonuclease - nuclear chromatin damage
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49
Causes other than hypoxia for cell injury?
- sequence of events for other insults may be different but as the cell has a limited responses to injury, outcome often similar
- other forms of injury might attach different key structures - extreme cold damages mebranes internally
- free radicals also damage membranes primarily
50
What is a free radical?
Reactive O2 species - single unpaired electron in an outer orbit - unstable configuration
OH, O2-, H2O2
51
How do you produce free radicals?
- normal metabolic reaction
- inflammation
- radiation
- contact with unbound metals within the body
- drugs and chemicals
52
How can you control free radicals?
- antioxidant system: donate electrons to the free radical - vitamins ACE
- metal carrier and storage proteins (transferrin, ceruloplasmin) sequester iron and copper
- enzymes that neutralise free radicals
53
How do free radicals injure cells?
Free radicals overwhelms the anti-oxidant system - oxidative imbalance
Most important target = lipids in cell membranes - causes lipid peroxidation
Oxidise proteins, carbohydrates and DNA - molecules have become bent out of shape - mutagenic and carcinogenic
54
How do protect the cell from injury?
- heat shock proteins - aims to mend misfolded proteins and maintains cell viability
- unfoldases or chaperonins
55
What will you see in hypoxic injured or dying cells under the microscope?
- cytoplasmic changes
- nuclear changes
- abnormal cellular accumulations
56
In reversibe cell injury what will be seen under the microscope?
- swelling of cells and organelles due to sodium-potassium pump failure
- cytoplasmic blebs
- clumped chromatin due to reduced pH
- ribosome detadchment due to failure of energy-dependent process of maintaining ribosomes in the correct location
57
In irreversible cell injury what will be seen under the microscope?
- increased cell swelling
- nuclear changes - pyknosis, karyolysis, karryorhexis
- swelling and rupture of lysosomes
- membrane defects
- appearance of myelin figures
- lysis of endoplasmic reticulum due to membrane defects
- amorphous densities in swollen mitochondria
58
Define oncosis?
Cell death with swelling, spectrum of changes tha occur in injured cells prior to death
59
Define necrosis?
In a living organism the morphological changes that occur after a cell has been dead for some time
60
Define apoptosis?
Cell death with shrinkage, cell death induced by a regulated intracellular program where a cell activates enzymes that degrade its own nuclear DNA and proteins
61
When is necrosis seen?
When there is damage to cell membranes and lysosomal enzymes are released into the cytoplasm and digest the cell - contents leak out of the cell and inflammation is seen - necrotic changes develop over a no of hours - necrotic tissue is removed by enzymatic degradation and phagocytosis by white cells -> can lead to dystrophic calcification
62
What is coagulative necrosis?
Cells are dying and their proteins denature and coagulate - ischaemia of solid organs - cellular architecture is somewhat preserved - ghost outline of cells
63
What is liquefactive or colliquitive necrosis?
Proteins undergo autolysis in which proteins undergo dissolution by the cells own enzymes - enzyme degradation is greater than denaturation - enzymatic digestion of tissues - ischaemia in loose tissues - preserve of many neutrophils
64
What are the two special types of necrosis?
Caseous necrosis - contains amorpheus debris - not as uniform as coagulative - looks like cheese - associated with infection e.g. TB
Fat necrosis - looks like bits of wax dropped on tissue
65
What is gangrene?
Necrosis visible to the naked eye
Exposure to air = dry gangrene - coagulative necrosis
Infection with a mixed bacterial culture = wet gangrene - liquefactive necrosis
Gas gangrene is wet gangrene where the tissue has become infected with anaerobic bacteria that produces visible and palpable bubbles of gas within the tissues
66
What is infarction?
Necrosis caused by a reduction in arterial blood flow
67
What is a red infarct?
RED = haemmorhagic infarct occurs where there is extensive haemmorhage into dead tissue - dual blood supple and numerous anastomoses - raised venous pressure, reperfusion and loose tissue
68
What is a white infarct?
WHITE = anaemic infarct occurs in solid organs after occlusion of an end artery e.g. thrombosis or embolism
69
What are the consequences of ischaemia?
- none
- death
Depending on: alternative blood supply, speed of ischaemia, tissue involved and O2 content of blood
70
What is ischaemia-reperfusion injury?
If blood flow is returned to a damaged but not yet necrotic tissue, damage sustained can be worse than if blood hadn't been returned - increased no of neutrtophils (inflammation), free radicals, complement proteins
71
Many molecules leak out of injured cells as their membranes are disrupted, for example...?
- causes local inflammation
- more general toxic effects
- high conc in blood
Potassium
Enzymes - aid in diagnosis
Myoglobin - released from dead myocardium and striated muscle
72
What is apoptosis?
Death of a single cell due to activation of an internally controlled suicide programme - can be a normal physiological process or can occur when a cell is damaged
73
What are the characteristic appearances of apoptosis?
- apoptotic cells are shrunken and appear intensely eosinophilic
- chromatin condensation, pyknosis and karryorhexis are seen and take on a distinctive appearance
- cytoplasmic budding
- apoptotic bodies are removed by macrophage
- no leakage of inflammation as there is no leakage of cell contents
74
What is the characteristic of DNA breakdown?
Not random, internucleosomal damage of DNA
75
When is apoptosis described as a physiological process?
Hormone controlled involution
| Embryogenesis
76
When is apoptosis described as a pathological process?
Cytotoxic T cell killing of virus infected or neoplastic cells
When cells are damaged, particularly with damaged DNA
77
What are the 3 phases of apoptosis?
Initiation
Execution
Degradation and phagocytosis
78
What are abnormal cellular accumulations?
If a cell cannot metabolise something it will remain in the cell
Can derive from:
- cell's own metabolism
- extraceullular space e.g. spilled blood
- outer environnment e.g. dust
79
What are the five main groups of accumulations?
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Water and electrolytes
Lipid - triglycerides and cholesterol
Proteins
Pigments
Carbohydrates
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80
What is pathological calcification?
Abnormal deposition of calcium salts within tissue - can be localised (dystrophic) or generalised (metastatic)
81
What is dystrophic calcification?
- occurs in an area of dying tissue, in atherosclerotic plaques, in aging or damaged heart valves and in TB lymph nodes
- no abnormality in calcium metabolism or serum calcium or potassium concentrations
- local change or disturbance in the tissue favours the nucleation of hydroxyapatite crystals
82
What is metastatic calcification?
Body wide disturbance - hydroxyapatite crystals are deposited in normal tissues throughout the body when there is hypercalcaemia secondary to disturbances in calcium metabolism
83
What is cellular aging?
They accumulate damage to cellular constituents and DNA - may also accumulate abnormally folded proteins
Decline in ability to replicate - related to length of chromosomes - with each division telomeres are shortened and when the telomeres reach a critical length, the cell can no longer divide
