Session 1 Flashcards

1
Q

Define disease

A

Pathological condition of a body part, organ or system characterised by an identifiable group of signs or symptoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is pathology?

A

The study of suffering (disease and cellular dysfunction)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Cytopathology involves the study of…

A

Disaggregated cells rather than tissues to study disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Histopathology involves the study of…

A

Tissues to study disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Give examples of histologcal procedures (3)

A

Core biopsies
Cancer resection specimens
Excised skin lesions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Give examples of cytological procedures (2)

A

Fine needle aspirates of breast/thyroid/salivary glands

Cervical smears

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Give 2 advantages of histological investigations/procedures over cytological investigations/procedures

A

Often therapeutic as well as diagnostic

Can assess architecture as well as cell atypia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Give 3 advantages of using cytological procedures/investigations over histological procedures/investigations

A

Faster and cheaper
Non-invasive or minimally invasive
Can be used for cells in fluid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

The staging of cancer often follows the TNM system which looks at…

A

Tumour
Nodes
Metastases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is autolysis? How can this affect microscopy of a tissue?

A

Self digestion of a tissue which occurs when the blood supply is cut off

Destroys cell and tissue architecture

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How can autolysis be prevented?

A

By use of fixatives that inactivate tissue enzymes, prevent bacterial growth and harden the tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What chemical is typically used in fixation of sample for microscopy? What change in appearance will the tissue show after the fixative is applied?

A

Formalin

Raw meat —> Cooked meat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Tissues that have been fixed are placed into a ________ with holes in it to allow the chemical to penetrate the sample

A

Cassette

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Why is it important for the tissue to be hard? What is this process called?

A

Allows the tissue to be cut into very thin slices

Embedding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is commonly used as the hardening agent when a tissue is embedded?

A

Paraffin wax

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Outline the process of embedding a tissue

A

Dehydration using alcohol in a vacuum
Alcohol replaced with xylene as it can mix with wax
Xylene replaced with molten paraffin wax

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Tissues are typically cut to what thickness? Using which piece of equipment?

A

~3-4 microns

Microtome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What stain is most commonly used to stain samples?

A

H & E stain

Haematoxylin + Eosin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What does haematoxylin stain the most?

A

The nucleus most strongly blue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What does eosin stain the most?

A

The EM (cytoplasm and connective tissue) most strongly pink

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the purpose of mounting a slice of tissue?

A

Preserves and protects the sample

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What does immunohistochemistry involve?

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are cytokeratins? What is the clinical significance of these?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Why are frozen sections sometimes taken?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Why are frozen sections not routinely used?

A

They provide a lower quality sample - cell morphology is not as good as in paraffin sections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What piece of equipment is used to take frozen sections?

A

A cryostat (microtome inside a freezer)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is hypoxia?

A

Decreased oxygen supply to certain cells/tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is ischaemia?

A

Decreased blood supply to certain cells/tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Why is ischaemia worse than hypoxia?

A

In ischaemia other nutrients such as glucose are also not supplied to cells/tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Name 4 types of hypoxia

A

Hypoxaemic hypoxia
Anaemia hypoxia
Ischaemic hypoxia
Histiocytic hypoxia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is hypoxaemic hypoxia? Give an example of a cause

A

Where the arterial content of oxygen is low - e.g. There is reduced absorption of oxygen in the lungs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is anaemic hypoxia? Give an example of a cause

A

Where there is decreased ability of haemoglobin to carry oxygen (e.g. In anaemia)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is ischaemic hypoxia? Give an example of a cause

A

Where there is interruption to blood supply (e.g. There is blockage of a vessel)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What is histiocytic hypoxia? Give an example of a cause

A

The inability to utilise the oxygen within cells (e.g. Damaged oxidative phosphorylation enzymes due to cyanide poisoning)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

The effects of hypoxia depends on…

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What are hypersensitivity reactions?

A

Where the host tissue is injured secondary to an overly vigorous immune reaction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What are autoimmune reactions?

A

Immune system fails to distinguish self from non-self

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What are free radicals?

A

Reactive oxygen species that have a single unpaired electron in its outer orbit making it unstable and more reactive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What are 3 significant free radicals? Which is the most dangerous?

A

OH* (hydroxyl)
O2- (superoxide)
H2O2 (hydrogen peroxide)

Hydroxyl

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

How are free radicals produced? (5)

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Haemachromatosis is caused by…

A

Excess of iron

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Wilson’s disease is caused by…

A

Excess of copper

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What controls do we have against free radicals? (3)

A

Anti-oxidant system

Metal carrier and storage proteins

Enzymes that neutralise free radicals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What does the anti-oxidant system consist of? How does it work against free radicals?

A

Vitamins A, C & E

They donate electrons to the free radical

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Give an example of a metal carrier protein that sequesters…

(I) iron
(II) copper

A

Transferrin

Ceruloplasmin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Give 3 examples of enzymes that neutralise free radicals.

A

Superoxide dismutase
Catalase
Glutathione peroxidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

How do free radicals injure cells?

A

They injure cell membranes and cause lipid peroxidation and then further free radicals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What is oxidative imbalance?

A

Where the number of free radicals overwhelms the anti-oxidant system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

As well as lipids, which other cell structures can be oxidised by free radicals? What are the consequences of this?

A

Proteins, carbohydrates, DNA

Causes mutations in DNA and can therefore be carcinogenic, also bends proteins out of shape

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What is the function of heat shock proteins?

A

During any cell injury, these proteins stop producing their usual products and aim to mend mis-folded proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What is karyolysis?

A

Nuclear fading - dissolution of chromatin due to action of DNAases and RNAases leading to cell death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What is pyknosis?

A

Nuclear shrinkage - DNA condenses into shrunken basophilic mass leading to cell death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What is karyorrhexis?

A

Nuclear fragmentation - nuclear membrane ruptures and nucleus undergoes fragmentation leading to cell death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

How will injured cells appear under the microscope?

A

Often pale and swollen due to poorer function of the membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Hypoxia can result in cytoplasmic changes, nuclear changes and abnormal cellular accumulations seen under the microscope what is an example of these abnormal accumulations?

A

Fat in hepatocytes

56
Q

What is an example of a reversible change that can be seen in an injured cell under an electron microscope?

A

Blebbing because the cytoskeleton is being broken down by proteases

57
Q

How can cell death be diagnosed?

A

Cells placed in fluid with a dye - dead cells with non-functioning membranes will take up the dye

58
Q

What is oncosis?

A

Cell death with swelling, the spectrum of changes that occur in injured cells prior to death

59
Q

What is necrosis?

A

In a living organism, the morphological changes that occur after a cell has been dead some time (after 12-24 hours)

60
Q

Name 4 types of necrosis

A

Coagulative
Liquefactive
Caseous
Fat

61
Q

Coagulative necrosis takes place in which sorts of tissues?

A

Solid organs with a lot of connective tissue support e.g. Kidneys

62
Q

Liquefactive necrosis takes place in which sorts of tissues?

A

Loose tissues e.g. Brain

63
Q

What happens in coagulative necrosis?

A

Denaturation of proteins dominates over the release of active proteases

64
Q

How does coagulative necrosis look under the microscope?

A

The cellular architecture is somewhat preserved with the ‘ghost outline’ of cells

65
Q

What happens in liquefactive necrosis? How does it appear under the microscope?

A

Enzyme degradation is substantially grater than denaturation and there is enzymatic degradation of tissues

resulting in no cell architecture being seen under the microscope

66
Q

What is caseous necrosis? In what cases is it most common?

A

Contains amorphous (structureless) debris - ‘cottage cheese’ appearance

In infections - especially TB

67
Q

What type of necrosis is particularly associated with infections such as TB?

A

Caseous necrosis

68
Q

Give two examples of where fat necrosis can be seen?

A

In pancreatitis

In the breast

69
Q

What happens in pancreatitis with regards to fat necrosis?

A

Digestive enzymes leak out into the abdominal cavity and break down lipids into fatty acids. Fatty acids react with calcium to form calcium soaps which are then deposited.

70
Q

What happens in the breast with regards to fat necrosis?

A

There is disruption of fat in the breast and a hard lump forms in the breast

71
Q

What is gangrene?

A

Necrosis visible to the naked eye

72
Q

What is dry gangrene?

A

Visible necrosis modified by exposure to air - commonly coagulative necrosis

73
Q

What is wet gangrene?

A

Visible necrosis modified by infection - commonly liquefactive necrosis

74
Q

What is gas gangrene?

A

Wet gangrene where the infection is with anaerobic bacteria that produce gas

75
Q

What is an infarction?

A

Necrosis caused by reduction in arterial blood flow

76
Q

What is an infarct?

A

An area of necrotic tissue which is the result of loss of arterial blood supply

77
Q

Name two common causes of infarction

A

Thrombosis

Embolism

78
Q

Infarcted tissue can appear which two colours?

A

White or red

79
Q

Where are white infarcts most common? What causes them? What is the reason for their appearance? What type of necrosis is commonly associated with white infarcts?

A

Solid organs e.g. Kidneys

There is usually occlusion of an end artery with no collateral blood supply

There is no blood haemorrhage into the area giving a white appearance

Coagulative

80
Q

Where do red infarcts commonly take place? What is the reason for their red appearance?

A

Loose tissues e.g. Lungs
There is haemorrhage into necrotic areas. There is often a dual blood supply with not enough blood to rescue the area but blood still pumping.

81
Q

What is ischaemia-reperfusion injury?

A

Worse damage that results from reperfusing ischaemic tissues. Results in…

Increased production of oxygen free radicals
Increased number of neutrophils and more inflammation
Activation of the complement pathway

82
Q

Leaky membranes can cause molecules to leak out of cells as well as in. What can leak out? What effect can each molecule have?

A

Potassium
Enzymes
Myoglobin

83
Q

What can too much calcium outside a cell result in?

A

Cardiac arrest

84
Q

Myoglobin can leak out of damaged skeletal muscle cells in response to…

What can it result in? (2)

A

Trauma/Extreme Exercise

Brown urine and renal failure

85
Q

What is apoptosis?

A

Cell death with shrinkage

86
Q

Does apoptosis require ATP?

A

Yes

87
Q

How does apoptosis work?

A

Activates enzymes that degrade its own nuclear DNA and proteins

88
Q

How is DNA broken down in apoptosis? How is DNA broken down in oncosis?

A

Inter-nucleosomal cleavage of dna

Random cleavage of DNA

89
Q

How is membrane integrity affected in apoptosis? Are lysosomal enzymes involved in apoptosis? How fast is the process of apoptosis?

A

Membrane integrity is maintained

No

Quick - few hours

90
Q

Give 3 physiological examples of apoptosis in the human body.

A

To maintain a steady number of cells

To reduce the size of ovaries after removal of oestrogen in post menopausal women

Apoptosis between the digits on a human hand

91
Q

Give 3 examples of pathological apoptosis in the human body.

A

Cytotoxic T cell killing of virus infected or neoplastic cells

Damaged cells with damaged DNA

Graft versus host disease

92
Q

What are the 3 phases of apoptosis?

A

Initiation
Execution
Degradation & Phagocytosis

93
Q

Apoptosis can be activated via ___________ or ___________ pathways. Both pathways result in the activation of ___________

A

Extrinsic or intrinsic

Caspases

94
Q

What are caspases?

A

Enzymes that control and mediate apoptosis, cause the cleavage of DNA + proteins

95
Q

What is meant by the intrinsic pathway of apoptosis? What typically triggers it?

A

Everything happens within the cell

Irreparable DNA damage

96
Q

What happens in the intrinsic pathway of apoptosis?

A

P53 protein is activated —-> Outer mitochondrial membrane becomes leaky —-> Cytochrome C is released from the mitochondria —-> Activation of caspases

97
Q

What is meant by the extrinsic pathway of apoptosis? What typically triggers it?

A

Initiated by extracellular signals

Cells that are a danger e.g. Tumour cells/virus infected cells

98
Q

What happens in the extrinsic pathway of apoptosis?

A

E.g. TNFalpha secreted by t killer cells in response to cells that are a danger —-> Bind to cell membrane death receptor (death receptor) —-> Activation of caspases

99
Q

What happens to the apoptotic bodies produced in the intrinsic/extrinsic pathways?

A

They express proteins on their surface that allow them to be recognised, phagocytosed and degraded by phagocytes or neighbouring cells

100
Q

Why does cellular accumulation occur?

A

As a result of a cell not being able to metabolise something

101
Q

What is meant by the term hydropic swelling?

A

Accumulation of fluid

102
Q

When does fluid accumulation occur?

A

When energy supplies are cut off - e.g. In hypoxia

103
Q

What happens in fluid accumulation?

A

Na+ and water flood into the cell

104
Q

Why is cerebral oedema a particular problem?

A

Increased pressure on the skull, structures in the brain/spinal cord get compressed - blood supply may be compromised

105
Q

What is steatosis? Where is it commonly seen and why?

A

The accumulation of triglycerides in a cell

The liver as it is a major organ of fat metabolism

106
Q

What are some common causes of steatosis?

A

Alcohol
Diabetes
Obesity

107
Q

Cholesterol can only be eliminated through the _______

A

Liver

108
Q

Is cholesterol soluble or insoluble?

A

Insoluble

109
Q

How is excess cholesterol stored?

A

In cells within vesicles

110
Q

In particular what two types of cells can cholesterol accumulate in?

A

Smooth muscle cells and macrophages

Produces foam cells

111
Q

How do accumulated proteins appear under the microscope?

A

As eosinophilic droplets in the cytoplasm

112
Q

What protein accumulations are seen in alcoholic liver disease?

A

Mallory’ hyaline - accumulation of damaged keratin filaments

113
Q

What causes alpha1-antitrypsin deficiency? What can it result in?

A

Incorrectly folded a1-antitrypsin proteins - accumulates in ER and leads to deficiencies as a result

Can lead to emphysema as proteases act unchecked in the lungs

114
Q

What are some examples of exogenous pigments that can accumulate in the body?

A

Air pollutants such as carbon, coal dust, soot

115
Q

What happens to pigments such as soot that are inhaled?

A

They are phagocytosed by alveolar macrophages resulting in anthracosis (blackening of the lungs) and blackened peribronchial lymph nodes

116
Q

Small amounts of pigment accumulation is usually harmless. Large amounts can result in…

A

Fibrosis and emphysema (coal worker’s pneumoconiosis)

117
Q

What happens to some of the pigment following a tattoo…

A

Some reaches and stays in the draining lymph nodes

118
Q

What is haemosiderin?

A

An endogenous pigment and iron storage molecule derived from haemoglobin

119
Q

What colour does haemosiderin have?

A

Yellow/brown colour

120
Q

When does haemosiderin form?

A

When there is a systemic or local excess of iron

121
Q

What happens when there is a systemic excess of iron?

A

Haemosiderosis - it is deposited in organs

122
Q

What can cause haemosiderosis? (3)

A

Haemolytic anaemia, blood transfusions and hereditary haemochromatosis

123
Q

What is the result of hereditary haemochromatosis?

A

Increased intestinal absorption of dietary iron and deposition of iron in organs (haemosiderosis).

124
Q

What are some symptoms of hereditary haemochromatosis?

A

Liver damage, heart dysfunction and endocrine failures

125
Q

What is the treatment for hereditary haemochromatosis?

A

Repeated bleeding?

126
Q

Jaundice is as a result of the accumulation of…

What colour does it have?

A

Bilirubin

Bright yellow

127
Q

How is bilirubin formed? In which cells of the body?

A

As a breakdown product of heme

All cells of the body

128
Q

How is bile excreted?

A

Taken from tissues bound to albumin to the liver and excreted in the bile

129
Q

When does jaundice occur?

A

When bile flow is obstructed or overwhelmed

130
Q

Where is bilirubin deposited in jaundice?

A

Extracellularly or in macrophages

131
Q

What is meant by the calcification of tissues?

A

Abnormal deposition of calcium salts within tissues

132
Q

Calcification of tissues can either be localised (___________) or generalised (__________)

A

Dystrophic

Metastatic

133
Q

Is dystrophic calcification more or less common than metastatic calcification? When does it occur? (5)

A

More common

In areas of dying tissue, atherosclerotic plaques, ageing or damaged heart valves, TB lymph nodes, malignancies

134
Q

What happens in metastatic calcification?

A

Hypercalcaemia in the blood as a result of abnormal calcium metabolism results in calcium hydroxyapatite crystals being deposited in normal tissues throughout the body

135
Q

What are two main causes of hypercalcaemia?

A

Increased secretion of parathyroid hormone (PTH) resulting in bone resorption (can be primary, secondary or ectopic)

Destruction of bone tissue

136
Q

After a certain number of divisions cells reach ____________ _____________ where they can no longer divide. This is related to the length of their ___________.

A

Replicative senescence

Telomeres

137
Q

What is the function of telomerase? Which types of cells produce telomerase?

A

Maintains the length of telomeres so cells can continue to replicate

Germ cells, stem cells and cancer cells