Final Exam Flashcards
What do pathologists do?
Pathologists analyze microbial tests to identify illness, characterize disease, use molecular genetics to increase the use of preventative medicine, and understand and treat disease with allocation of resources.
What is pathology?
Pathology is the study of disease, looking at its cause, effects, current state, treatments, and outcomes with tests and procedures.
Explain the patient journey.
The ideal patient journey shows how Canada’s healthcare system is ideally built to manage disease.
Well: subjective state of health defined by factors and social determinants
Health Decline: decline in health that can be managed by the patient or treated with prescription medication
Triage: patient presents themselves at a hospital or is taken by ambulance and seen by a triage nurse that assesses the urgency of treatment and care.
Admittance: patient is admitted when their illness is too severe, is unidentified and needs further testing, or requires treatment and monitoring by specialists
Diagnosis: tests are done to assess the condition. This is the stage where families begin to seek support
Treatment: after given a diagnosis and prognosis, the patient and physician discuss treatment options
Discharge: patient is sent home with medication and follow-up support
Monitoring: patients have check-ins so that physicians can monitor compliance and treatment safety
Palliative Care: patient is made comfortable until death
Explain the disease paradigm.
The disease paradigm is used to conceptualize the characteristics of a disease.
Etiology: the root cause of the disease
Pathogenesis: the development mechanisms of the disease
Testing: tests are done to analyze the presence of the disease
Biochemical Changes: changes to the chemical processes in the body seen through the test results
Morphological Changes: how the change in cells and tissues appear
Functional Changes: changes to physiology that appear in symptoms
Natural History: the prognosis of the disease
Treatment: how the disease is treated
Complications: further complications that can be caused by the disease
At what stage in the patient journey do pathologists play the largest role?
The primary role of pathologists in healthcare is to determine a diagnosis of the patients ailment.
How do indigenous groups learn and inherit knowledge?
Indigenous groups learn through experiential learning which is actively done through observation, action, and reflection. This learning is strengthened by ancestors, guides, and the Creator to form views on disease.
They inherit knowledge through oral tradition with the use of songs, poems, storytelling, and prayers. They have identified individuals who carry oral tradition. These people are knowledge keepers who remember and recite history, longhouse leaders who recite traditional speeches, and elders who tell stories to influence behaviour.
How do indigenous individuals view health?
Indigenous groups view health through a holistic perspective, viewing systems as wholes with inclusion of the four interconnected dimensions that are expressed on the medicine wheel.
Spiritual: cultural safety, strength, and resilience
Physical: capacities, mobility, comorbidity, awareness, and prevention
Mental: housing, family, community, and ceremony
Emotional: causality, and access to services
What are cells?
Cells are the basic unit structure of life that are composed of DNA. They differentiate into specialized cells that work together to do functions of tissues, in organs, within body systems, that come together as the human body. They always need nutrients, waste removal, and oxygen and are subjected to stresses that cause the cell to die and be replaced by new cells.
Define and explain the function of the cells organelles. (10)
Plasma membrane: made of phospholipids that control what can enter and exit the cell. Some molecules can freely pass through the membrane while others cannot. The molecules that can’t freely pass require transporters or the binding of receptors.
Nucleus: contains the genome within DNA that replicates, transcribes, and translates.
Mitochondria: produces energy in the form of ATP with the use of the Krebs cycle and oxidative phosphorylation.
ER: transports molecules around the cell and produces proteins and lipids.
Golgi apparatus: packages protein and cargo into vesicles for transport.
Lysosomes: digest waste and destroy bacteria with the use of enzymes.
Endosomes: sort, store, and organize content that comes into the cell.
Peroxisomes: break down hydrogen peroxide producing molecules and reactive oxygen species to neutralize the cell. Peroxisomes also need neutralized by catalase as they can be dangerous to the cell.
Cytoplasm: fluid within the plasma membrane with tightly regulated composition.
Cytoskeleton: structure filaments that provide structure and generate force for motion.
Explain the Central Dogma.
The central dogma covers the main parts of cellular function: replication, transcription, and translation.
Replication: cell duplicates it’s DNA before dividing
Transcription: DNA is transcribed into RNA
Translation: mRNA is translated into amino acid sequences that fold into proteins
How does gene regulation occur?
Gene regulation gives gene expression profiles by turning genes on or off, allowing an effective response to stimuli.
1) ligand binds to a receptor
2) receptor initiates cellular signalling
3) the signal up-regulates transcription of specific proteins
4) transcription produces mRNA
5) mRNA is translated into a protein
6) the protein is secreted from the cell so that it can do its function
Briefly explain the cell cycle.
G0: nerve and muscle cells are in a state of rest
G1: cells are actively living and growing in preparation to divide
S: genome replication occurs
G2: cell grows, increasing its amount of organelles
M: mitosis occurs where organelles are reorganized or dissolves, chromosomes are lined up and moved to each side of the cell, and cytokinesis divides the cell into two daughter cells
What are stem cells?
Stem cells are asymmetric cells that can differentiate into specialized cells to preform a function. They are extremely important for cellular repair or replacement. Stem cells specialize into progenitor cells that can differentiate into specialized cells to renew damaged tissue.
Briefly explain the two processes of cell death.
Necrosis is a result of trauma that causes the cell the real ease harmful reactive oxygen species and enzymes that cause inflammation and cell death in surrounding cells.
Apoptosis is regulated cell death that causes the cell to release its components without inducing inflammation.
What is cancer?
Cancer is the uncontrolled growth and division of abnormal cells that have the ability to invade tissues. It is the number one cause of death to Canadians.
What are neoplasms and tumours?
A neoplasm is abnormal tissue that grows when cells divide and do not die. A tumour is swelling or an abnormal mass that can be benign or malignant. Benign tumours cannot spread, can become large without killing the patient, and have a smooth round contour. Malignant tumours are cancerous tumours that can metastasize, kill patients when they are small, and have a spiky contour.
What is metastasis?
Metastasis is the ability of malignant tumours to spread around the body, through the bloodstream, to colonize different sites. This is what makes controlling cancer difficult as it can spread through the body, killing patients and making it difficult to determine the tumours place of origin. To find its place of origin, full body imaging and gene expression is used.
What are the different classifications of cancer? (5)
Carcinoma: solid tumours that affect epithelial cells
Sarcoma: begin in tissues that support the body like fat, muscle, nerves, blood vessels, bone, and tendons
Lymphoma: cancer that begins in lymphocytes
Glioma: arise in connective tissues of the brain
Leukaemia: cancer of the blood and bone marrow
What are the risk factors of cancer?
Family history, tobacco, age, HPV, and UV radiation are all carcinogens with tobacco being the most preventative. Generally tissues with higher stem cell divisions are at a higher lifetime risk of cancer.
Tobacco leads to the accumulation of tissue damage and the smoke kills epithelial cells so that stem cells need to repair the damage. The stem cells rapidly divide to restore the epithelial level and return to a resting state. With repeated exposure to smoke, stem cell division occurs more often, increasing the risk and vulnerability to oncogenic mutations.
Genetics are a major factor in cancer as a mutation occurs due to chromosomal damage that alters genes.
Direct UV exposure causes cumulative damage that increases the risk of damaging the genome which then accumulates to provide selective growth advantages, allowing mutated cells to thrive.
How does cancer start and evolve?
Cancers starts with a single cell that undergoes an oncogenic mutation. Typically mutations are silent, which don’t change the amino acid sequence or protein produced, or oncogenic which directly contributes to cancer development. The first step of cancer development is transformation, where a normal cell undergoes a genetic change that leads to a tumour cell that can divide rapidly. Over time, the tumour cells divide, causing an accumulation of mutations in daughter cells that can be the same as the initial tumour cell, or genetically different with other mutation variants. These cells are called clones. As the tumour cells proliferate, additional mutations occur, forming subclones that derive from the initial clone, which provide further growth advantages. With various sets of different mutations, the cancer is heterogenous representing hundreds of different cancer cells and subclones that offer different physiological characteristics.
Compare oncogenes and tumour suppressor genes.
Oncogenes derive from proto-oncogenes that mutate into oncogenes and produce proteins with altered functions that are involved with growth receptor pathways to mediate homeostasis and injury repair. Oncogenes only require 1 mutated allele and are typically form a sporadic type of cancer.
Tumour suppressor genes, when mutated, disable the ability of cells to prevent growth and induce cell death. These genes require both alleles to be mutated and typically are a familial type of cancer.
Explain the TP53 gene.
The TP53 is a tumour suppressor gene that produces p53 protein to regulate division. p53 Response to genomic damage by activating repair or cell death that prevents mutated cells from dividing. p53 Deficiency allows the cell to thrive with oncogenic mutation. Initially, the p53 binds to damaged DNA inducing G1 cell cycle arrest and repair with transcription. Proteins must repair mutations to proceed, but if that fails p53 triggers apoptosis or senescence. With inactive p53 no cell cycle arrest or repair occurs and damaged cells can proliferate into tumors.
Explain the ERBB-1 gene
ERBB-1 is an oncogene that encodes for epidermal growth factor receptors (EGFR). There are 20 different EGFR Proto-oncogenes that detect ligands, form dimers, and transmit signals associated with growth or survival to prevent unwanted proliferation. EGFR is a tyrosine kinase receptor that induces gene expression. initially a ligand binds to a receptor causing a confirmational change. Secondary messengers are then phosphorylated to transmit signals to the nucleus inducing transcription for proliferation, migration, and angiogenesis. Afterwards, the ligand releases or the receptor is broken down to stop the signal. Is there is a mutation to the ERBB-1, hyperactivation occurs where more secondary messengers are activated increasing the signal response and pro cancer processes. It also induces constitutive activation where signals are sent without a stimulus so pro cancer processes do not stop.
How does colorectal cancer develop?
Colorectal cancer arises from epithelial neoplasms called adenomas that are in the mucosa. Their development begins when cells with oncogenic mutations hyperproliferate. The mass that grows then projects into the intestinal lumen as a colonic polyp that takes 7 to 10 years to progress and can be removed in that time. Without removal, the polyp eventually invades adjacent tissue layers causing adenocarcinoma. The cancerous stage is when the polyp grows and evades tissues by entering the bloodstream to metastasize
How is screening and removal done for colorectal cancer?
Screening detects cancer early so that it is easier to treat. This is done on patients with increased risk of cancer due to age or family history. For colorectal cancer, a fecal immunochemical test which examines stool for blood from polyps, colonoscopy that looks for any masses, and CT scan which use medical imaging with x-rays to check for metastasis can be completed. Typically people do not get screened because of fear, lack of family history, misconception, or costs.
To remove colorectal cancer, a hemicolectomy can be done to remove the part of the colon that contains cancer and its surrounding lymph nodes.
How are tumours characterized?
Histology looks for changes to tissue structure to determine tumour progression by cutting and staining thin sections of tissue. Tumours are characterized by their stage and grade.
Stages of cancer include T, N, and M. The T indicates the depth of invasion, N indicates the spread to lymph nodes, and M denotes the presence or absence of metastasis. Lower stage numbers indicate less progression and better outcomes.
Cancer grades show how abnormal cells appear on a scale of 0 to 4 where higher numbers show more abnormality. Normal cells have hollow glands while G1 have less circular glands, G2 have different cells shapes, G3 has less glands and a variation in shape, and G4 have no glands, are not hollow, and do not have a specific structure.
What is genetic testing done on colorectal cancer patients done for?
When patients have colorectal cancer, genetic counsellors can get a blood test to see if there’s a mutation in the MSH2 gene of non-cancer cells to confirm Lynch syndrome. Lynch syndrome is a hereditary non-polyposis colorectal cancer that is the most common hereditary colorectal cancer syndrome. It is caused by a germline mutation to a mismatch repair gene. Since lynch syndrome is hereditary, one allele is already mutated so only one more mutation needs to occur for cancer to develop.
What is sporadic and familial colorectal cancer?
Sporadic: mutation spontaneously occurs on both alleles of the APC gene
Familial: inherited mutation of the mismatch repair genes (MSH2)
What affects the prognosis of colorectal cancer?
The prognosis of colorectal cancer depends on prognostic factors like age, general health, response to treatment, stage and grade, genetics, access to care, and compliance.