Module 1 & 2 Flashcards
1
Q
What is a pathologist?
A
A disease expert
2
Q
What does a pathologist do?
A
Identify, characterize (physically and genetically), and allocate treatment for diseases
3
Q
What is pathology?
A
The study of disease (cause, effect, test, procedures)
4
Q
What are the stages of the patient journey?
A
well, health decline, triage, admittance, diagnosis, treatment, discharge, monitoring, palliative care
5
Q
What is defined as well?
A
No care is needed, they are not a patient
6
Q
What is a health decline?
A
Can manage issue with little help
7
Q
What is triage?
A
patient goes to a hospital, presents signs and symptoms in front of a healthcare professional and severity is assessed
8
Q
What is the admittance stage?
A
patient’s condition is bad enough that it needs treatment
9
Q
What is diagnosis?
A
Tests are ordered and condition is analyzed, support is recommended
10
Q
What is point of care testing?
A
real time testing
11
Q
What is the treatment stage?
A
patient is informed of diagnosis and options are discussed
12
Q
What is prognosis?
A
The likely development of the disease
13
Q
What is the discharge stage?
A
Conditional release following illness
14
Q
What is the monitoring stage?
A
regular check ins to monitor progression
15
Q
What is the palliative stage?
A
Care until death
16
Q
What things can hinder the ideal patient journey?
A
Fear of medical system, systemic racism, lack of access, etc..
17
Q
What are the parts of the pathology disease paradigm?
A
ethology, pathogenesis, testing, biochemical changes, morphological changes, functional changes, natural history, treatment, complications
18
Q
What is ethology?
A
The root cause of the disease (ex. mosquito bite)
19
Q
What is the pathogenesis?
A
mechanism through which a disease acts
20
Q
What is testing?
A
Any examinations done on the patient
21
Q
What are biochemical changes?
A
Changes in chemical levels
22
Q
What are morphological change?
A
Changes to tissues
23
Q
What are functional changes
A
Changes to the way the individual functions
24
Q
What is the natural history?
A
Prognosis
25
What is the treatment?
The methods through which the disease is combatted
26
What are the complications?
Anything out of the ordinary that has a negative impact
27
What is experiential learning?
learning by actions, observations, reflection, and further action
28
How is knowledge inherited in Indigenous traditions?
orally
29
Who were knowledge keepers?
individuals with good memory who carry for tradition and oral accounts (treaties, events, histories, etc...)
30
What were the ceremonial speeches?
speeches that a leader must be able to recite
31
What is storytelling?
the telling of indigenous tradition, some only with permission
32
What is relationality?
everything is related
33
What is spirituality?
Everything is spiritual
34
What is ontology?
Organizing info
35
What is epistemology?
theory of knowledge
36
What are the values of learning?
courage, love, wisdom, respect, truth, humility, honesty
37
What is holism?
The idea that systems should be viewed as wholes and not parts
38
What are the 4 dimensions of the medicine wheel?
emotional (black), spiritual (white), physical (yellow), and mental (red)
39
How do Indigenous and Western cultures view medicine/
Western: scientific and physiological.
Indigenous: Holistic
40
What is an ally/
someone who recognizes colonialism, tries to change patterns, and educate self and others
41
What can aspiring allies do?
try to fix power imbalances, self-critique, be willing to listen, be okay with discomfort, get support from other allies
42
What is a bystander?
Someone who denies or ignores systemic racism
43
What is an accomplice?
Someone who works within the system or organization to challenge racism or discrimination
44
What is a co-resistor?
someone who combines theory and practice and works along side others to resist racisms
45
What are cells?
The basic unit of life
46
What are tissues?
more specialized cells that function together
47
What are organs?
Groups of tissues that perform the same function
48
What are systems?
groups of organs working together
49
What is the human body?
A group of systems working together
50
What is the plasma membrane?
A phospholipid semi-permeable membrane with receptors and transporters
51
What is the nucleus?
Site of DN storage replication, transciption
52
What is the mitochondria?
produces ATP from hydrocarbons through the Krebs cycle
53
What is the ER/Golgi apparatus?
protein/lipid synthesis, while the Golgi sorts and transports molecules
54
What are lysosomes?
break down cellular materials and waste products
55
What are endosomes?
Storage and organization
56
What are peroxisomes?
H2O2 and ROS breakdown
57
What is cytoplasm?
Fluid with organelles
58
What is the cytoskeleton?
structural filaments
59
What the central dogma?
replication->transcription->translation
60
Does every cell have the same DNA?
Yes
61
How do cells specialize if they all have the same DNA?
Genes are turned on or off
62
How does gene regulation allow for responses to environmental stimuli?
ligand binds to a receptor, which results in a signal cascade to nucleus, where transcription is regulated, resulting in either increased or decreased protein product
63
What is DNA mutation?
Changes in DNA sequence resulting in changes to proteins, leading to disease
64
What are the stages of the cell cycle?
G0, G1, S, G2, M
65
What is the G1 phase?
The growth phase of cells where they accumulate mass
66
What is the G1 checkpoint?
where cell is checked to see if it is big enough to replicate DNA
67
What is the S phase?
DNA is replicated
68
What is the G2 phase?
Second phase of growth
69
What is the G2 checkpoint/
Where DNA is checked
70
What is the M phase?
Mitosis
71
What is the G0 phase?
Cell gets shunted into this phase if it did not meet growth requirement
72
Can cell division be asymmetric?
yes
73
What happens if cell division is asymmetric?
different genetic expression
74
What are Stem Cells?
Specialized cells that can divide to produce new stem cells in a process called self-renewal
75
Where are Stem Cells found?
all throughout the body
76
What are progenitor cells?
cells with the potential to divide and differentiate into many different cell types. Caused by asymmetric cell division
77
What is differentiation?
When progenitor cells divide into a specialized cell type, and must commit to just one cell type
78
Can progenitor cells dedifferentiate into stem cells?
No
79
What is tissue renewal?
Tissue division to replace dead or sloughed off cells
80
What is the result of uncontrolled cell division?
A neoplasm
81
What is necrosis?
Death caused by a severe lack of resources or trauma. Causes the release of harmful chemicals like enzymes and ROS, which can damage and inflame surrounding tissue
82
What is apoptosis?
Controlled and regulated cell death
83
What is an example of apoptosis?
breakdown of finger webbing in-utero
84
What is cancer?
the uncontrolled growth of abnormal cells in the body
85
What percentage of Canadians will receive a cancer diagnosis in their lifetime?
50%
86
How has the age standardized mortality of cancer changed?
It has decreased although it is still a leading cause of death
87
What is a neoplasm?
any abnormal tissue that forms when cells grow and divide more than they should, or do not die when they should
88
What is a tumour?
A non-specific term for a neoplasm
89
What defines a benign tumour?
inability to invade and spread, can attain sizes greater than 50kg without killing the patient, smooth round contours like a sea spong
90
What defines a malignant tumour?
can invade into other tissues, can kill before 50g, spiky, reminiscent of a crab
91
What is metastasis?
The invasion of other tissues by a malignant tumour via the blood stream. A major mechanism through which cancer kills
92
How can the orgin of a malignant tumour be determined?
Through full body imaging/gene expression
93
What is carcinoma?
effects epithelial cells and forms solid tumours
94
What is sarcoma?
affects tissues that support and connect the body like fat muscle nerve tendons cartilage, bone, etc..
95
What is lymphoma?
begins in the lymphocytes
96
What is glioma?
connective tissue of the brain
97
What is leukaemia?
cancer of the blood and bone
98
What is the ultimate cause of cancer/
mutations
99
What is the risk of cancer proportional to?
The likelihood that a cancerous mutation will occur
100
What is the incidence of Cancer in First Nations relative to the rest of Ontario?
higher, with female breast and male prostate highest, with colorectal after
101
What is the mortality for First Nations with cancer compared to Ontario?
Significantly higher with the exception of leukaemia in males
102
What are common risk factors for cancer?
family history, tobacco use, aging, UV radiation
103
What percentage of cancers are preventable?
30-50%
104
What are common misconceptions regarding carcinogens?
that wifi, microwaves, GMOs, and deodorant can cause cancer
105
How do cells repair following tobacco use?
epithelial cells are killed, then stem cells rapidly divide asymmetrically and repair dmg, then stop dividing
105
How does tobacco use result in cancer?
chronic injury, division, reinjury causes stem cell mutations that permanently cause division
106
How does risk of cancer change over time with UV exposure?
It is cumulative and increases
107
How does number of cell divisions relate to risk of cancer?
As number of divisions increase, risk of cancer increases
108
How does exposure to mutagens change cancer risk?
It increases it
109
What is an oncogenic mutation?
A mutation that directly contributes to cancer
110
What is a silent mutation?
A mutation with no effect
111
What are the stages of the evolution of cancer?
transformation, progression, proliferation, tumour heterogeneity
112
What is transformation?
normal cell undergoes mutations and becomes a tumour cell
113
What is progression?
tumour cell division leads to accumulation of mutations in daughter cells, called variants. These are clones
114
What is proliferation?`
sub clones with different growth advantages form as cell proliferate
115
What is tumour heterogeneity?
Tumours can be made up of many clones and sub clones with different characteristics
116
What are common cancer mutations?
preventing apoptosis, escaping the immune system, ability to enter and exit blood vessels
117
What is the challenge with treating different cancers?
tissues respond to treatment differently and different cells respond differently due to heterogeneity
118
Can multiple tumours arise from one cell?
yes
119
What are oncogenes?
mutated genes that produce proteins that confer new growth advantages
120
What are proto-oncogenes?
genes that become oncogenes usually involved in growth-receptor pathways
121
What is sporadic cancer?
cancer in an individual with no family history. associated with oncogenes
122
What are tumour suppressor genes?
genes that prevent uncontrolled cell growth and control cell death
123
What happens when tumour suppressor genes are mutated?
inability to apoptose and and continuous growth?
124
How many alleles must be mutated before the mutation can contribute to cancer?
2
125
What are familial cancers?
Cancers with a clear familial component. associated with tumour suppressor genes
126
What is the two-hit hypothesis?
just one allele of a tumour suppressor gene can handle the workload, so two mutations must occur to support cancer. Some families have one allele that is already non functional?
127
What is change in the potential for cancer if a family already has a non-functional allele of a tumour suppressor gene?
1:1e9 -> 1:1e6
128
Can you be born with cancer?
No. growth is highly controlled by proto-oncogenes and tumour suppressor genes in-utero
129
What is the TP53 gene?
A tumour suppressor gene on chromosome 17 that is mutated in some capacity in nearly all cancers
130
What is the product of TP53?
p53, a protein that regulates cell division
131
How does p53 work?
Determines cell death and survival by responding to genomic dmg through repair/cell death programs during the G1/S phase of the cell cycle
132
How does a non-functional p53 cause cancer?
allows cancer causing mutations to survive
133
How is p53 activated?
damaged DNA leads to p53 accumulation and binding to specific sites, arrest of cell cycle, and transcriptional up regulation of repair genes
134
How is DNA repaired following p53 activation?
By the products of the repair genes. if successful, cycle continues, if fails, apoptosis or senescence
135
What is senescence?
A state in which a cell cannot replicate
136
What is ERBB-1?
A proto-oncogene that codes for Epidermal Growth Factor Receptor (EGFR) located on chromosome 7
137
What is EGFR?
A signal receptor tyrosine kinase that dimerizes in order to transduce signal and kickoff growth processes
138
What happens when ligands bind to EGFR?
dimerization activates
139
What happens when EGFR dimerizes?
It autophosphorylates and and phosphorylates secondary messengers which transduce signal to nucleus
140
What happens when EGFR transduces a signal to the nucleus?
increased transcription of genes for angiogenesis, proliferation, migration adhesion and invasion, and apoptosis inhibition
141
How is EGFR signal controlled?
Terminated by ligand release or receptor breakdown via lysosomes
142
What occurs when ERBB-1 is mutated to be oncogenic?
hyper-activation or constitutive activation
143
What is hyper-activation?
More secondary messengers are activated from the same amount of ligand, increasing pro-cancer processes
144
What is constitutive activation?
signalling without ligands, meaning constant pro-cancer activities
145
How does chemo affect EGFR?
doesn't target EGFR directly but will kill any rapidly dividing cell in the body
146
How do antibodies affect EGFR?
EGFR domain is extracellular, making it a good target
147
What is antibody-based therapy?
antibodies are injected into the body causing inactivation/destruction of the target protein via immune system activation
148
How do kinase inhibitors affect EGFR?
Since EGFR and 2ndary messengers have kinase activity, small molecule inhibitors can cross the plasma membrane, disrupting signalling cascades
149
What is a challenge to preventing cancer in indigenous communities?
smoking has a high prevalence and is traditional and ceremonial
150
How has Indigenous smoking prevalence been combatted?
2009, chiefs of Ontario passed resolution to become free of commercial tobacco
151
What is the Indigenous Tobacco Program?
A program that urges Indigenous peoples to become tobacco wise and to avoid commercial tobacco use
152
What is a challenge to diagnosing Indigenous people with cancer?
They are less likely to get screened due to distrust and limited access to healthcare
153
What is a challenge to treating cancers?
drug resistance due to mutations. common is recurrent cancers?
154
Why is it difficult to treat cancers that have metastasized to the brain?
Many cancer targeting drugs cannot cross the brain-blood-barrier
155
Who is Aaliyah?
A 59yo woman from small town ontario suffering from Iron-deficiency anemia, a symptom of GI cancer, leading her to be referred to a gastroenterologist
156
What is Iron Deficiency Anemia?
An inability to make sufficient RBCs stemming from iron deficiency
157
What testing did Aaliyah's gastroenterologist perform?
an upper endoscopy and a colonoscopy to visualize the digestive tract
158
What was found in Aaliyah's colon?
A mass indicating colorectal cancer. a biopsy of the mass was performed
159
What type of cancer is colorectal cancer?
adenoma arising from benign epithelial neoplasms
160
What are the stages of development of colorectal cancer?
hyper proliferation, adenomatous polyp, pre-cancerous polyp, adenocarcinoma, advanced cancer
161
What is hyperproliferation in colorectal cancer?
1 or more oncogenic mutation and the cells begin to hyperproliferate
162
What is the adenomatous polyp stage in colorectal cancer?
when a rapidly dividing mass of cells projects into the intestinal lumen. called colonic polyps
163
What is the pre-cancerous polyp stage in colorectal cancer?
a malignant growth that can take 7-10 years to become cancerous. Can be removed pre-malignancy
164
What is the adenocarcinoma stage in colorectal cancer?
the cancer becomes invasive and cells divide into adjacent tissue layers
165
What is the advanced cancer stage in colorectal cancer?
further growth/metastasis of the cancer
166
How does colorectal cancer affect immigrants and Indigenous pops.?
Indigenous populations have increased incidence and mortality while immigrants have lower incidence, as the cancer is connected to diet
167
What groups are primarily screened for colorectal cancer?
Older patients and patients with a family history
168
What is the fecal immunochemical test?
A test that examines stool for trace amounts of blood. For 50-70yo, every 2 years.
169
What individuals require colonoscopies?
Those at increased risk
170
What are some of the reasons people don't get tested for colorectal cancer?
fear of difficulty or pain, no family history, misconception that you need symptoms, concern about cost or scheduling
171
What was performed on Aaliyah to determine if the cancer had metastasized?
A CT scan. No evidence of metastasis was found.
172
What was performed on Aaliyah to get rid of the cancer?
A hemicolectomy to remove the tumour and surrounding lymph nodes
173
What is a hemicolectomy?
A surgery where part of the large intestine is removed and the two ends are joined back together
174
How is histology used to observe tumours?
Used to view changes in normal tissue structure
175
What was the result of Aaliyah's histological analysis?
The cancer had invaded lower tissue layers but had not spread to the outer border
176
What are the 3 classifications for describing solid tumours?
T (depth of invasion 0-4), N (spread to lymph nodes 0-4), and M (metastasis 0-4)
177
What is grading in cancer?
describes the abnormality of the cells in the biopsy of the cancer appear
178
What characterizes a normal cell in the grading system?
colon cells form glands, cells appear hollow and larger glands have a space in the middle
179
What characterizes a G1 cell?
nearly all cells still form glands, cells are less circular, hollow appearance lost, may grow into central space
180
What characterizes a G2 cell?
some gland formation still visible, additional loss of circular gland structure, cell shape drastically different, central gland space occupied by cells and necrosis debris
181
What characterizes a G3 cell?
little gland formation present, cells vary in shape and size, only a few cells continue to exhibit normal hollow appearance
182
What characterizes a G4 cell?
glands practically non-existent, no trace of hollow appearance/central space, no specific structure
183
What was Aaliyah screened for genetically?
Lynch Syndrome
184
What did Aaliyah's genetic tests find?
mutated MSH2 gene. She was then sent to a genetic counsellor to see if MSH2 is in non-cancerous cells
185
What is common in sporadic colorectal cancer?
somatic mutations on both alleles of adenomatous polyposis coli gene
186
What is common in familial colorectal cancer?
inherited mutation in mismatch repair gene such as MSH2
187
What is the scientific name for Lynch syndrome?
Hereditary Nonpolyposis Colorectal Cancer Syndrome. Most common hereditary colorectal cancer syndrome
188
What must Aaliyah do post-genetic counselling?
routine screening as she is at risk for other cancers, kids should be regularly screened as they have a 50% chance of having the gene
189
How is a prognosis for colorectal cancer developed?
Age and overall health, responsiveness to treatment, stage and grade, genetics, and screening and compliance are all taken into account
190
Who is Jorge?
A 37yo man with shortness of breath and lower energy, with a. nosebleed that hadn't stopped for 7 days, along with an intermittent fever over the next two weeks
191
What is collected during blood work?
concentrations of blood cells and clotting factors
192
What did Jorge's blood work suggest?
low Hb, High WBC, High percent blasts, and low platelets suggest leaukemia
193
How are blood cancers diagnosed?
Through malignant cells in the blood
194
Where do blood cancers begin?
In the bone marrow
195
What causes blood cancers?
A failure of stem cells to mature into blood cells
196
What do blood cancers affect a patient?
Cause fatigue, bleeding, and clotting issues
197
What is the percentage of Canadian cancers that are blood cancers?
10% of cancer diagnoses
198
What is the impact of blood cancer on FN communities?
lower incidence, higher mortality
199
What is hematopoiesis?
The development of mature blood cells from hematopoietic stem cells in the bone marrow
200
What are hematopoietic stem cells?
11000-22000 cell with a long lifespan that differentiate into progenitor cells
201
What are common myeloid and lymphoid progenitor cells?
Multipoint cells that can differentiate into a subset of blood cells. myeloid progenitors produce blasts which fully differentiate into different blood cells
202
What are specialized myeloid cells?
RBCs, Platelets, specific WBCs
203
What are specialized lymphoid cells?
T-cells, B-cells, natural killer cells
204
What is the relationship between hematopoiesis and blood cancer?
blood cancer arise when HSCs proliferate and fail to fully differentiate
205
What is the classical blood cancer pathway?
Differentiation block, enhanced proliferation, blood cancer
206
What is a differentiation block?
tumour suppressor gene is lost in HSCs or common progenitor leading to blast accumulation
207
What is enhanced proliferation?
proto-oncogene mutation resulting in increased proliferation
208
What was the result of Jorge's blood smear?
blasts in the blood were promyelocytes, a precursor to WBCs, meaning the cancer is Acute Myeloid Leukemia
209
What does acute mean regarding blood cancer?
poorly differentiated cells accumulate and progress rapidly, requiring immediate treatment
210
What does chronic mean regarding blood cancer?
well-differentiated cells accumulate and progress slowly, meaning the disease can be monitored before treatment
211
What are prognostic factors for leukemia?
age, weight, previous blood disorders, genetics
212
What does myeloid mean in blood cancer?
the cancer arose from a myeloid progenitor
213
What is lymphocytic mean in blood cancer?
The caner arose from a lymphocyte progenitor
214
What did Jorge's genetic test reveal?
PML-RARA translocation
215
What is a chromosomal translocation?
A break and incorrect fusion of chromosomes
216
What does chromosomal translocation result in?
fusion proteins with the potential to be oncogenic
217
What is PML-RARA?
A translocation between chromosome 15 and 17 at the site of the PML and RARA genes
218
What is RARA?
A gene that codes for RAR-a protein that is inactivated in a healthy cell to allow differentiation to occur
219
What is the PML-RARA fusion protein?
A hybrid that is not inactivated for differentiation
220
What does ATRA treatment do?
Allows for blasts to fully differentiate by targeting PML-RARA fusion protein
221
How is clinical cancer care evolving?
to be more patient centred and holistic
222
How is cancer a mosaic of diseases?
since there are hundreds of different types of cancers and each tumour can produce sub clones, there are many unique cases
223
How does immunotherapy work?
By using immune checkpoint inhibitors to allow the immune system to attack cancers
224
What are biomarkers?
A measurable indicator of some state or condition in the body (ex small chemicals, enzymes, DNA, RNA, Cancer Cells, protein
225
What are diagnostic biomarkers?
Detects and confirms the presence of a disease
226
What are prognostic biomarkers?
predicts the likelihood of disease progression or recurrence
227
What are predictive biomarkers?
predicts response to particular treatment
228
What are developments in gene sequencing regarding cancer?
human genome project, next generation sequencing, tumour sequencing, data analysis, application
229
How can the well stage be improved in cancer treatment?
screening for at risk pops, although compliance and access are still problems
230
What are examples of cancer screening tools?
Pap smears, mammograms, FIT and colonoscopy, and digital rectal exams
231
What are common treatments for cancer?
surgery, radiation, chemo, immunotherapy, sometimes in combination
232
What complicates cancer treatment?
difficulty in access
