PATH 120 Final Exam Review

Definition of pathology

The study of disease, including the causes and effects of disease, and the tests and procedures that determine disease states.

What is the primary role of a pathologist throughout the patient journey?

To diagnose the disease.

Steps of the ideal patient journey

1. Well

2. Health decline

3. Triage

4. Admittance

5. Diagnosis

6. Treatment

7. Discharge

8. Monitoring

9. Palliative care

Ideal Patient Journey - Well

maintenance of wellbeing

subjective

no medical intervention

Ideal Patient Journey - Health Decline

manage themselves or with primary care

possible medication

Ideal Patient Journey - Triage

if not able to handle on their own

start showing symptoms

tertiary care - hospitals

assess severity of illness to find priorities

Ideal Patient Journey - Admittance

3 reasons

- condition too severe

- issue not identified yet

- patient stabilized but needs treatment

Ideal Patient Journey - Diagnosis

tests ordered to characterize disease

diagnostic testing

informs decisions on treatments and identifies disease

Ideal Patient Journey - Treatment

patient informed of diagnosis and prognosis and treatment options

treatment is executed

Ideal Patient Journey - Palliative Care

when treatments unsuccessful

primary goal to make patient as comfortable as possible

preserve or improve quality of life

Ideal Patient Journey - Discharge

after successful treatments

released from care if can prove access to prescriptions as well as follow up treatments

Ideal Patient Journey - Monitoring

check ins regularly

could last years and need more tests

sometimes completely cured, sometimes cannot be cured

goal is to restore to "well"

Disease pathology paradigm

1. Etiology/cause

2. Pathogenesis/mechanisms of action

3. Testing

4. Biochemical/morphological/functional changes

5. Natural history/prognosis

6. Treatment

7. Complications

Etiology

the cause of disease

Pathogenesis

development of disease

mechanism of action of disease

biochemical changes

alterations in how cells and body metabolizes things

ex. build up of substances

Morphological Changes

structural or tissue changes in response to disease

cellular level or tissue level

Functional Changes

symtpoms associated with the disease

ex. loss of mobility

Testing

determines if disease is present and identify the specific disease

ex. DNA sequencing, blood glucose levels, histologies, neurological assessments

Natural history

prognosis

likely outcome for the patient

Treatment - disease paradigm

management and care of patient to combat the disease

complications

short and long term effects of disease and other factors

can alter natural history and treatments

Etiology of strep throat

Bacterium streptococcus pyogenes

Pathogenesis of strep throat

Streptoccous pyogenes adheres and invades lining in the nasal and oral cavities

Testing of strep throat

A rapid strep test that looks for Streptococcus pyogenes antigens

Biochemical changes of strep throat

Bacteria secretes tissue-damaging enzymes to lining of throat

Morphological changes of strep throat

Tissue-damaging enzymes cause an immune response and inflammation observed as redness and swelling in the tonsils.

Functional changes of strep throat

Inflammation causes pain when swallowing.

Prognosis of strep throat

Symptoms usually improve within 3-5 days, irrespective of treatment.

Treatment of strep throat

Antibiotics (penicillin) that kill bacteria

Complications of strep throat

Rheumatic fever (inflammatory disease causing permanent heart damage) in low-middle income countries where strep throat goes unnoticed. It takes 1-5 weeks to develop.

Indigenous values

1. Storytelling to promote values within culture

2. Medicine wheel to consider holistic perspective of health

3. Sharing circles to give everyone a chance to speak and learn

4. Knowledge keepers to remember and pass on history

5. Ceremonial speeches passed on through oral tradition

6. Relationality in learning with fellow students, family, and the land

6. Spirituality. Epistemologies and ontologies are rooted in sacred and secular world-views

7. Grandfather teachings (honesty, courage, love, wisdom, respect, truth, and humility)

Traditional medicine wheel dimensions

1. Emotional

2. Spiritual

3. Physical

4. Mental

Emotional Health - Indigenous

causality

access to equipment and services

Mental health - indigenous

housing

family

community

ceremony

physical health - indigenous

capacities

mobility

comorbidity

awareness and prevention

spiritual health - indigenous

cultural

safety

strengths

resilience

What is an ally

knows unearned privilege

responsibility for changing patterns

educates self and others

unlearning and relearning

continuous process

Stages of Allyship

Bystander

- ignores issues

- does nothing

Ally

- educes self and others

Accomplice

- works to change the systems

Co-resister

- standing together with marginalized groups

Levels of organization in the body

1. Cells

2. Tissues

3. Organs

4. Systems

5. Human body

The plasma membrane is made up of a double layer of _________________.

Phospholipids

What are phospholipids?

Specialized lipid molecules that have both hydrophobic (water-repelling) and hydrophilic (water-loving) structures.

What are membrane transporters?

Integral-membrane proteins that form a pore within the plasma membrane to allow passage of various types of molecules, including ions, small molecules, and proteins that cannot enter cells freely (like oxygen, carbon dioxide, and some hormones).

What is a receptor?

A protein which binds to a specific molecule called a ligand.

Function of the nucleus

Contains our genome, stored in the form of DNA. It is where DNA is replicated in preparation for cell division, and where DNA is transcribed to mRNA. These are the first 2 steps of the central dogma of molecular biology.

Function of the mitochondria

Powerhouse of the cell, producing large amounts of energy for cells to use. It is where fats are broken down for energy, where the Krebs cycle occurs, and where ATP (cellular currency) is produced through oxidative phosphorylation.

Function of the endoplasmic reticulum

Where proteins are translated and processed. As well, plays a role in the transporting of molecules around cells, and makes many fats.

Function of the golgi apparatus

Processes and packages proteins and cargo into vesicles to send them to final destinations inside or outside the cell.

Function of lysosomes

Digest waste products and damaged cellular material, and destroy viruses or bacteria engulfed by the cell.

Function of endosomes

Transport vesicles that sort, store, and organize contents inside our cells, as well as those entering and exiting from the outside environment.

Function of peroxisomes

The enzyme catalase neutralizes and breaks down hydrogen peroxide and reactive oxygen species and the molecules that produce them.

Function of the cytoplasm

Fluid contained within the plasma membrane where all other organelles are found. Chemical composition (pH, ionic concentrations, etc.) is highly regulated.

Function of the cytoskeleton

Composed of a dense network of specialized structural filaments that add structure and shape to cells. It also generates force for cellular movement and is how the cell internally transports cargo in vesicles along its microtubules and actin filaments.

Central dogma of molecular biology

1. DNA replication in the nucleus

2. Transcription in the nucleus

3. Translation in the cytoplasm or endoplasmic reticulum

What is gene regulation?

The ability to turn genes on and off, and the ability of a cell to respond to internal or environmental stimuli, called gene expression signals.

What is a mutation?

Change in DNA sequence that can be repaired. If repair fails, mutant proteins can be produced that exhibit altered function which may lead to disease.

Phases of the cell cycle

1. Gap 0 (cell is resting - often nerve and muscle cells are found in this state) *technically not part of cell cycle

2. Gap 1 (cell is actively growing) *majority of lifespan

3. Synthesis (cells replicate genomes)

4. Gap 2 (last chance for cell to grow before division) *cytoplasm and organelles grow

5. Mitosis (cell division, concluding with cytokinesis)

What is asymmetric cell division?

Two daughter cells arising from mitosis that are genetically identical, but that have different gene expression (e.g., stem cells).

What are stem cells?

Cells that can differentiate into progenitor cells through asymmetric cell division. They are specialized cells that can divide to produce new stem cells in a process called self-renewal.

What are progenitor cells?

Have the potential to divide and differentiate into many other cell types.

What is progenitor-cell differentiation?

Progenitor cells divide to replace specialized cells that are damaged or lost, and must commit to only one differentiated cell type. They cannot de-differentiate back into stem cells.

What is tissue renewal?

Blood cells, skin cells, and cells lining the gut are continuously dividing to replace dead or sloughed-off cells.

What is necrosis?

Cell death caused by a severe lack of resources necessary for life like oxygen, or from severe trauma, freezing or physical injury. It results in the release of harmful chemicals like reactive oxygen species and enzymes, which cause inflammation and damage to the surrounding tissue.

What is apoptosis?

Carefully regulated cell death that does not induce inflammation and occurs frequently in the natural developmental process (like when a fetus losses webbed fingers in womb).

What is cancer?

The uncontrolled growth/dividing of abnormal cells in the body that invade and potentially spread to other tissues.

What is the leading cause of death among Canadians?

Cancer

What is a neoplasm?

Any abnormal tissue that forms when cells grow and divide more than they should, or when they don't die when they should. This can refer to harmless growths of cells like skin tags or cancerous growths.

What is a tumour?

A non-specific term for a neoplasm that simply means "mass" and is any swelling or abnormal enlargement in or on the human body. These can be benign (harmless, cannot invade or spread to other tissues) or malignant (cancerous, invade other tissues).

What is metastasis?

When malignant tumours spread to other areas of the body via the bloodstream. It is the mechanism by which most cancers kill.

difficult to control

What size does a malignant tumour have to be to spread and kill?

50 grams

What size can a benign tumour grow to, without harming the patient?

50 kilograms

Appearance of benign vs malignant tumours

Benign = smooth and round contour (sea sponge)

Malignant = spiky contour (crab)

What is a carcinoma?

A type of cancer that affects epithelial cells (cells that line skin, blood vessels, urinary tract, organs) usually forming solid tumours (cancers of the prostate, breasts, lungs, and colorectal).

What is a sarcoma?

A type of cancer that begins in tissues that support and connect the body (fat, muscles, nerves, tendons, joints, blood vessels, lymph vessels, cartilage, or bone).

What is a lymphoma?

A type of cancer that begins in the lymphocytes, the infection fighting cells of the immune system found in glands, nodes, and other lymphoid tissues.

What is a glioma?

A type of cancer that arises from the connective tissues of the brain, called glial cells, which support neurons, causing brain and spinal cord cancers.

What is leukemia?

A type of cancer of blood and bone marrow cells, occurring when healthy blood cells change and grow uncontrollably.

What is a glioblastoma?

A form of glioma that arises from cells called astrocytes.

Which tissues have almost a 0% chance of giving rise to cancer?

Tissues of the heart, epididymis, and seminal vesicle.

First Nations Cancer Incidence

higher incidence in FNMI

colorectal cancer highest

First Nations Cancer Prevalence

most prevalent cancers are breast and prostate, next is colorectal

First Nations Cancer Mortality

most types have higher mortality than Ontario population

lower mortality from leukemia

First Nations Cancer Survival

5 year survival significantly lower than Ontario population

Definition of prevalence

A measure of total active cases of a disease in a population.

Definition of incidence

A measure of the number of new occurrences of a disease in a population.

Which are the most prevalent cancers in Canada?

Lung, blood, breast, prostate, and colorectal.

Which are the most prevalent cancers among Indigenous Canadians?

Female breast and male prostate cancer, as well as colorectal cancer.

Proven risk factors of cancer (carcinogens)

Family history (genetics), tobacco use, age, HPV infection, and UV radiation.

What is the most common cause of preventable cancer?

Tobacco

Development of cancer from exposure to tobacco smoke

1. Tobacco exposure: Toxic chemicals from smoke can kill the epithelial cells that line the airway and lungs.

2. Injury: When epithelial tissue dies, specialized stem cells exit resting state and repair damage through rapid asymmetrical cell division.

3. Repair: In the normal healing process, the epithelial layer is eventually restored and stem cells stop dividing.

4. Resting state: Stem cells exit the cell cycle and go back to rest.

5. Persistent activation: Because stem cells are moving and growing, they might be vulnerable to oncogenic mutations. Heavy smokers who repeatedly expose stem cells to chemical mutagens permanently activate stem cell growth.

6. Cancer: Cancer is ultimately caused through this injury hypothesis.

Which tissue types are most susceptible to becoming cancerous?

Those with higher rates of stem cell divisions

Genetic cancer

disorder caused by mutation of 1+ genes through chromosomal damage or combination of mutations and environment

Not all cancers are preventable

more than half are caused by bad luck

despite healthy lifestyles, cells can still mutate

usually avoided through protective mechanisms like DNA repair and immune system - sometimes cell escapes

Silent Mutations

no change in amino acid sequence

Oncogenic mutation

leads to development of cancer

Stages of cancer evolution

1. Transformation (normal cell's genetic code is mutated leading to a tumour cell).

2. Progression (tumour cells divide and create many tumour cell variants that are distinct clones).

3. Proliferation (additional mutations provide tumour cells with further growth advantages and eventually many subclones with different mutations but derived from a single tumour cell form)

4. Tumour heterogeneity (hundreds of genetically different cancer cells exist in the same tumour, with different metastatic, invasive, and drug resistant properties).

What is an oncogene?

A cancer-associated gene that, once mutated, will produce proteins with new or altered functions which provide selective growth advantages to cancer cells.

involved in growth factor receptor pathways

one mutation is enough

What is a proto-oncogene?

The unmutated form of an oncogene which produces normal proteins. Normally involved in growth factor receptor pathways that mediate regulated embryonic growth, homeostasis, and injury repair.

How many alleles must be mutated for a proto-oncogene to ellicit pro-cancer effects?

Only one allele

Are oncogenes more closely associated with sporadic or familial cancers?

Sporadic