Session 1 - Intro + Cell Injury And Death Flashcards
1
Q
What is pathology?
A
Study of disease and cellular dysfunction
2
Q
What is chemical pathology?
A
Biochemical investigations of disease
3
Q
What is haematology?
A
Diseases of blood
4
Q
What is immunology?
A
Diseases of immune system
5
Q
What is medical microbiology?
A
Disease causing microbes including advice on antibiotic usage
6
Q
What are 3 differences between histology and cytology?
A
Histology is more detailed, cytology is more general
Cytology faster and cheaper than histology
Histology studies tissues, cytology studies single cells
7
Q
What is autolysis?
A
Self digestion of a tissue when blood supply is cut off
8
Q
What can block autolysis?
A
Fixatives
9
Q
What are 3 functions of fixatives?
A
Inactivate tissue enzymes and denature proteins
Prevent bacterial growth
Harden tissue
10
Q
What is used as fixatives?
A
Formalin (formaldehyde in water)
11
Q
How long to fix tissue?
A
24-48 hours
12
Q
Why is embedding necessary?
A
Hardens tissue to cut tissue into very thin sections
13
Q
What is use to embed tissues?
A
Paraffin wax
14
Q
What are 2 things to do before embedding in paraffin wax?
A
Dehydrate tissue using alcohol in a vacuum, replace alcohol with xylene
15
Q
What is the process of slicing tissue called?
A
Micro to my
16
Q
How thin are the sections of tissue?
A
3-4 microns
17
Q
What equipment is used to slice the tissues?
A
Microtome
18
Q
What stain is the most commonly used?
A
H&E
19
Q
What does Hematoxylin stain?
A
Nuclei purple or deep blue
20
Q
What does eosin stain?
A
Cytoplasm and connective tissue pink
21
Q
What is immunohistochemistry?
A
Show substances in a cell by labeling them with specific antibodies which are joined to an enzyme which catalyze a color producing reaction (usually brown)
22
Q
What is molecular biology?
A
Study of how diseases are caused by alterations in normal cellular molecular biology (changed DNA RNA or protein)
23
Q
What are frozen sections?
A
Method of hardening tissue quickly in 10-15 mins, usually to establish presence and nature of a lesson and influence course of operation
24
Q
What are the 7 steps of preparing slides for microscopy?
A
Fixation using formalin Trimming Dehydration using alcohol in vacuum then xylene Embedding using paraffin wax Microtomy using microtome Staining using H&E Mounting on slide and coverslip
25
What are the 8 causes of cell injury?
```
Hypoxia
Toxins
Physical agents (trauma, temperature changes, pressure changes)
Radiation
Micro organisms
Immune mechanisms
Nutritional
Genetics
```
26
What are 4 causes of hypoxia?
Hypoxaemic, anaemia, ischaemic, histiotoxic
27
What is hypoxaemic hypoxia?
Arterial content of oxygen is low, possible due to reduced O2 at high altitudes or reduced absorption due to lung disease
28
What is anaemia hypoxia?
Decreased ability of haemoglobin to carry oxygen
29
What is ischaemic hypoxia?
Interruption to blood supply
30
What is histiotoxic hypoxia?
Inability to utilize oxygen in cells due to disabled oxidative phosphorylation enzymes
31
What are the 2 ways that the immune system damages cells?
Hypersensitivity reactions and autoimmune reactions
32
What are hypersensitivity reactions?
Host tissue is injured due to an overly vigorous immune reaction
33
What are autoimmune reactions?
Immune system fails to distinguish self from non self
34
What are 4 cell components most susceptible to injury?
Plasma membrane
Mitochondria
Nucleus
Proteins
35
What causes reversible cell injury?
Reversible hypoxia = ischaemic hypoxia = blockage of blood vessels, less oxygen delivered, decreased oxidative phosphorylation in mitochondria, lesser ATP produced:
Na-K pump fails, increase in Ca2+ influx and water = cellular swelling, blebs
Increased glycolysis = lesser pH and lesser glycogen = nuclear chromatin clumps
Detachment of ribosomes = decreased protein synthesis = lipid deposition
36
What are the 4 effects of reversible injury?
Cellular swelling
Blebs
Nuclear chromatin clumps
Lipid deposition
37
What causes irreversible cell injury?
Influx of calcium (from outside of cell, mitochondria and ER)
Activates ATPase = reduced ATP
Activates phospholipase = damage membrane
Activates protease = damage membrane and cytoskeleton proteins
Activates endonuclease = nuclear chromatin damage
38
What are free radicals?
Molecules with single unpaired electron in outer orbit, very unstable and can react with other molecules
39
What are 3 main free radicals?
Hydroxyl OH-
Superoxide O2-
Hydrogen peroxide H2O2
40
What are 3 components free radicals target to cause cell injury?
Lipids peroxidation = cell membrane damage
Oxidation of amino acid side chains = protein fragmentation
React with thymine = causes DNA mutations
41
What is oxidative stress?
Imbalance between free radicals generation and radical scavenging systems
42
What are 2 forms of body control of free radicals?
Anti-oxidants donate electrons to the free radicals
| Enzymes neutralize free radicals
43
What are 3 examples of anti-oxidation?
Vitamins A, C and E
44
What are 3 examples of enzymes that neutralizes free radicals?
Superoxide dismutase
Catalase
Glutathione peroxidase
45
What is a form of body control of free radical damage?
Heat shock proteins mend misfolded proteins and maintain cell viability
46
What are 3 changes of an injured cell under a light microscope?
Cytoplasmic changes
Nuclear changes
Abnormal cellular accumulations
47
What are 3 forms of nuclear changes?
Pyknosis - chromatin condense
Karyorrhexis - nuclear fragmentation
Karyolysis - nuclear dissolution
48
What are 6 signs of reversible injury under an electron microscope?
```
Blebs
General swelling
ER swelling
Dispersion of ribosomes
Nuclear chromatin clumping
Mitochondrial swelling
```
49
What are 4 signs of irreversible injury under an electron microscope?
Rupture of lysosomes
Nuclear changes
Defective cell membrane
ER lysis
50
What is oncosis?
spectrum of changes that occur in injured cells prior to death
51
What is necrosis?
Morphological chances that occur 12-24 hours after cell death
52
What is apoptosis?
Programmed cell death
53
What is coagulative necrosis?
Denaturation of proteins dominates over release of active proteases, cellular architecture preserved, occurs in solid organs
54
What are the 2 ways to identify coagulative necrosis?
Ghost outline of cells
| Eosinophilia
55
What is liquefaction necrosis?
Enzyme degradation greater than denaturation, happens in loose tissues
56
What is caseous necrosis?
Contains structureless debris
57
What is fat necrosis?
Death of fat cells
58
What is an example of physiological apoptosis?
Embryogenesis
59
What is an example of pathological apoptosis?
Cytotoxic T cells killing virus infected cells
60
What are the 3 stages of apoptosis?
Initiation
Execution
Degradation and phagocytosis
61
What are the 2 ways of triggering apoptosis?
Intrinsic and extrinsic pathway
62
How does the intrinsic pathway trigger apoptosis?
Initiating signal comes from within cell (irreparable DNA damage or withdrawal of growth factors or hormones) activates p53 protein, causing outer mitochondrial membrane becoming leaky, releasing cytochrome C from mitochondria, causing activation of caspases
63
How does the extrinsic pathway trigger apoptosis?
Initiated by extracellular signal (TNFalpha released by tumor cells or virus infected cells), binds to cell membrane receptor (death receptor), results in activation of caspases
64
What happens after caspases activation?
Cells shrink and up into apoptotic bodies that express proteins on their surface, so they can be recognized by phagocytes and degraded by them
65
What are 2 differences between apoptosis and necrosis?
Cells shrinks in apoptosis and swells in necrosis
No inflammation in apoptosis but present in necrosis
Single cell in apoptosis and groups in necrosis
Intact membrane in apoptosis and disrupted in necrosis
66
What is gangrene?
Necrosis visible to the naked eye
67
What is infarction?
Necrosis caused by reduction in arterial blood flow
68
What is infarct?
An area of necrotic tissue which is the result of loss of arterial blood supply
69
What is white infarct?
Caused by coagulative necrosis in solid organs, often wedge shaped
70
What is red infarct?
Infarcts in loose tissue, with dual blood supply
71
What does the severity of infarction depend on?
Presence of alternative blood supply
Speed of ischaemia
Tissue involved
Oxygen content of blood
72
What is ischaemia reperfusion injury?
Blood flow returned to a damaged but not yet necrotic tissue, damage sustained is worsened
73
What are the 3 types of abnormal cellular accumulations after cell injury?
Normal cell components (water, lipids, proteins)
Abnormal components
Pigment
74
What are 4 mechanisms of intracellular accumulations?
Abnormal metabolism
Alterations in protein folding and transport
Deficiency of critical enzymes
Inability to degrade phagocytosed particles
75
What is steatosis?
Accumulation of triglycerides
76
What causes steatosis in the liver?
Chronic alcohol misuse
Obesity
Diabetes
77
What causes accumulation of cholesterol?
Mutations in LDL-R, abnormalities in apoproteins and lipoproteins
78
What is atherosclerosis?
Cholesterol build up in smooth muscle cells and macrophages, leading to atherosclerotic plaque
79
What is Xanthoma?
Cholesterol in macrophages within skin or tendons
80
What is cholesterolosis?
Accumulation of cholesterol laden macrophages in gallbladder
81
What is amyloidosis?
Proteins accumulated in extracellular space
82
What is alpha 1 anti trypsin deficiency?
Liver produces incorrectly folded alpha 1 antitrypsin proteins, cannot be packaged by ER so accumulates there, cannot be secreted. So proteases in lung act unchecked leading to emphysema
83
What is 2 examples of exogenous pigment to be accumulated?
Soot inhaled into lungs
Tattooing, pigment phagocytosed by macrophages in dermis and emails there
84
What is an example of a endogenous pigment?
Haemosiderin which is an iron storage molecule from haemoglobin, present in bruises
Bilirubin, breakdown product of haemoglobin, present in jaundice
85
What are 3 molecules released during cell injury?
Potassium
Enzymes
Myoglobin from dead myocardium and striated muscle
86
What is dystrophic pathological calcification?
Abnormal deposition of calcium salts localized in dying tissue
87
What is metastatic pathological calcification?
Generalized, deposition in otherwise normal tissue due to hypercalcaemia due to dysfunction in calcium disturbance
88
What are the 4 effects of hypercalcaemia?
Bones - bone disease
Stones - renal stones
Abdominal groans - pain, vomiting
Psychic moans - psychosis
89
What causes hepatic steatosis?
Fatty acids are converted to triglycerides in liver
alcohol alters mitochondrial function of hepatocytes
protein malnutrition decreases synthesis of aoproteins, cannot transport fats away
Starvation increases fatty acid mobilization from peripheral stores
90
How does steatosis appear under microscope?
Macrovesicular - larger fat bubbles
| Microvesicular - smaller fat bubbles
91
What is liver cirrhosis?
Fibrosis occurs in liver, liver becomes shrunken, can lead to chronic liver dysfunction
92
What is acute alcoholic hepatitis?
Acute liver failure - liver enlarges, deranged liver enzymes
93
What is replicative senescence?
Decline in ability to replicate, telomeres shortened with every replication and when reached critical length, cell cannot divide
