PATH120- Queens

Pathology

The study of disease- Focuses on causes of disease, and resulting effects on our cells and bodies

Medicine Wheel

Anishinaabe perspective used to consider the different ways of thinking about our balance as humans

Our connection to; Emotional, Spiritual, Physical, and Mental Wellbeing

What does a Pathologist do?

• Analyze microbiological test results to identify patients illness

• Characterize diseases- Can influence how they are treated

Ideal Patient Journey in Healthcare System

1. Well

2. Health Decline

3. Triage

4. Admittance

5. Diagnosis

6. Treatment

7. Discharge, Monitoring, Palliative Care

Well

• Before someone becomes a patient, they begin as a healthy individual 

• Their current lifestyle will serve to maintain this baseline State of Wellness

• Wellness can be subjective

Health Decline

• Could be 1+ contributing factors;

  • Genetics, infection, injury, nutrition, environment, access to care

• Patient will typically manage issue alone or with help of a primary care team 

  • If needed, may be prescribed medication

Triage

• If a disease progresses, patient may not be able to manage alone

• May decide to go to hospital

• Process of determining the severity of disease or illness, to decide the priority of treatment among patients

  • Decision will be made to send patient home or admit them for additional testing

Admittance

3 common reasons;

• Condition too severe to send home

• Issue has not been identified, and there's cause for concern 

• Patient has stabilized, but needs to receive treatment and to be monitored

Diagnosis

• Tests ordered by specialists better characterize the disease 

• Samples can be sent for lab analysis or imaging (Ex. X-ray, MRI)

• Increased use of Point-of-Care Testing- Medical diagnostic testing at time/place of patient care, allowing physicians to collect real-time testing results 

• Results from tests will be used to assess condition- Then inform decisions on the proposed treatment plan

Treatment

• After patient informed of diagnoses and prognosis

  • All treatment options will then be discussed- Could include: Medication, Minimally invasive procedures, Surgery, Long term medical interventions

Discharge

• In case of successful treatment

  • Patient will be monitored in-hospital, then released

• Likely conditions for release

  • Prescription drugs, follow up support from medical personnel

Monitoring

• Patients expected to check in regularly with hospital to ensure treatment was effective 

  • May last for years

• Could require additional visits for further testing

Palliative Care

• In case of unsuccessful or unavailable treatments 

  • Patients condition is terminal 

• Main goal becomes making patient as comfortable as possible until death

Point-of-Care Testing

Medical diagnostic testing at time/place of patient care, allowing physicians to collect real-time testing results 

Pathology Disease Paradigm

1. Etiology

2. Pathogenesis

3. Biochemical Changes

4. Morphological Changes

5. Functional Changes

6. Testing

7. Natural History

8. Treatment

9. Complications

Etiology

Root cause/origin of disease

Pathogenesis

Mechanism of action, Development of disease

Biochemical Changes

• How cells and body alter in metabolism

• May be a buildup of substances due to the disease

  • Or loss of essential substances needed for health

Morphological Changes

• Structural or tissue changes in response to disease

• Cellular tissue level changes in appearance

Functional Changes

Symptoms associated with disease

Testing

• Can determine if a disease is present and identify disease

• Many different kinds- ex. DNA sequencing, MRIs

• Biochemical, Morphological, Functional Changes all examined using ___

Natural History

Progression of the disease, Determines the prognosis/outcome

Complications

• Short and long-term effects of disease itself

• Other factors that may impact the disease and patient

• May alter natural history and treatment for an individual

Treatment

• Management and care of a patient to combat disease or disorder

• Can be short or long term

Experiential Learning

• Method of learning and understanding in Indigenous culture

• Actively done on land through activities such as; 

  • Crafting, walking, working, moving, building

Experiential Learning- Knowledge from Actions

•  A preference for learning through; Observation, action, reflection, and further action

• A method for sharing and learning from direct experience- Passing knowledge down through generations

Experiential Learning- Disease Knowledge and Treatment

• Ancestral knowledge contains stories of symptoms being observed within members of the community 

  • Recording which traditional remedies were most effective

Oral Tradition

A collection of spoken words kept alive by Knowledge keepers of the community

• May be in form of; Stories, poems, prayers, songs

Knowledge Keepers

• Responsible for carrying forward teachings or stories

• Trained to remember history, treaties, important events for community 

• At times, asked to recite historical accounts and/or speeches so people can remember and learn from past

Storytelling

• Told to teach, influence behavior, explain things in the natural world and for enjoyment 

• Some are considered “right-to-tell”- Require permission from a Knowledge Keeper, Elder, to be told

Relationality in Learning

• Concept that we are all related to each other, to natural environment, and spiritual world

• Emphasis on learning in relationships with fellow students, teachers, families, community members, and the land

Spirituality in Learning

• Indigenous Ontologies- Organizing information into categories and concepts

• Knowledge Epistemologies

  • Both are rooted in worldviews that are inclusive of both the sacred and secular

7 Grandfather Teachings

Courage, Love, Wisdom, Respect, Truth, Humility, Honesty

Holism

Idea that systems should be viewed as wholes instead of by their individual parts

Western Medicine

Typically designed to address the physiological cause and symptoms of disease

• Pathology acting as the bridge between etiology and treatment

Traditional Indigenous Medicine

Holistic approach to health maintenance and recovery- Recognizing and treating all aspects of disease at once

Allyship

A declaration of accountability for injustices suffered by marginalized populations

Tissues

Groups of cells that function together

Organ

Contained collection of tissues that perform a shared function (ex. Heart, Liver)

System

Groups of organs working towards a common purpose (ex. Endocrine, Immune, Reproductive)

Plasma Membrane

• Outer ‘skin’ of cell

• Contains all of cells organelles

• Controls what enters/leaves cell 

• Made of a double layer of Phospholipids

• Some molecules can pass freely through (Ex. Oxygen, CO2)

  • Others cannot, require Transporters

Nucleus

• Contains genome- Stored in form of DNA

• Where DNA is replicated in preparation for cell division 

• Where DNA is transcribed to messenger RNA (mRNA)

  • Later translated into protein outside nucleus 

Mitochondria

• “Powerhouse” of the cell

• Produces large amount of energy for cells to use

• Where fats are broken down for energy 

• Where Krebs Cycle takes place

• Where ATP is produced through oxidative phosphorylation

Endoplasmic Reticulum (ER)

Where many proteins are translated and processed- Similar to a factory 

• Lipids (fats) made here

• Plays role in transporting molecules around cell- To final destination

Golgi Apparatus

“Post Office”- Where processing and packing of proteins, etc. into Vesicles- Small lipid-bound structures that contain cargo (ex. proteins)

• This happens before being sent to final destinations inside or outside the cell

Lysosomes

• Digest different waste products and damaged cell material

• Able to destroy any viruses and bacterias

• Enzymes inside break down waste and debris

  • Digest proteins, lipids, nucleic acids, into their basic building blocks

Endosomes

• Transport vesicles that sort, store, and organize cell content

  • As well as those entering and exiting from the outside environment 

Peroxisomes

• Involved in the breakdown of hydrogen peroxide and reactive oxygen species, and the molecules that produce them 

• Can cause damage if not neutralized by the enzyme Catalase

Cytoplasm

• Key structural element to maintain cell shape

• The fluid contained within the plasma membrane 

  • Where all other organelles and cellular components are found

• Chemical composition tightly regulated- Cellular processes require specific conditions

Cytoskeleton

• Key structural element to maintain cell shape

• Acts as both skeleton and muscular system of cells

• Composed of a dense network of specialized structural filaments that add necessary structure to otherwise shapeless cells

• Generates force for cellular movement

• How cell internally transports cargo in vesicles along its microtubules and actin filaments throughout the cytoplasm

The Central Dogma of Molecular Biology

• Describes the flow of genetic information

• Process by which the instructions in DNA are made into protein products

1. Replication

2. Transcription

3. Translation

Replication

Occurs when a cell duplicates all of its genomic DNA prior to dividing

• So each daughter cell gets a copy

Transcription

Cells ____ the sequences in DNA into RNA sequences

Translation

• mRNA ____ into amino acid sequences- Fold to make proteins

• Proteins are ____ in the cytoplasm or ER

  • Then folded and processed to be sent to its final destination in the cell

Gene Regulation

• What creates the difference in cells

• Allows a cell to effectively respond to internal or environmental stimuli

Gene Expression Profiles

Cells that have different structural and functional characteristics will have different genes turned on/off

Mutations

Changes in the DNA sequence of a cell

DNA Repair

Cellular mechanisms capable of restoring a mutation back to its original sequence

The Cell Cycle

• Cells normally remain same size

• Cells divide in response to events- Ex. Tissue damage, growth signals

• Describes a series of events that take place in prep for, during, and after division

1. Gap 0 Phase

2. Gap 1 Phase- Active Growth

3. S Phase- Synthesis

4. Gap 2 Phase- Cell Growth

5. Mitosis- Cell Division

Gap 0 Phase (G0)

• Not part of cell cycle

• Phase that cells may enter when not actively dividing

Gap 1 Phase (G1)

• Cells in this phase are active and growing

  • Not yet committed to undergoing division 

• Cells must pass through a Checkpoint to start cell division

  • Checkpoint- A control mechanism that ensures a process has been accurately completed before progress into the next phase begins

• Majority of cells lifetime is spent in this phase 

S Phase (S)- Synthesis

• Cells replicate their entire genomes in preparation for division

  • Each daughter cell will receive a full copy of 23 chromosomes found in each somatic human cell

Gap 2 Phase (G2)

• Last chance for cells to grow before division

• DNA is checked before committing to dividing 

• Total amount of cytoplasm and size of organelles (ex. Golgi apparatus) increases during this growth phase

Mitosis (M)

• Cells are reorganized for cell division

• Protein synthesis is halted- DNA must be carefully packaged in preparation of division 

• The ER, cytoskeleton, and other organelles are all reorganized

  • Nucleus dissolves 

• Once chromosomes move to opposite ends of cell, organelles reform

• Concludes with cytokinesis- Cell finally divided into 2 separate daughter cells

Stem Cells

• Specialized cells that can divide to produce new stem cells 

  • Process called self-renewal, can happen over several cell cycles

  • Found in tissues throughout our bodies 

Necrosis

• Caused by severe lack of resources necessary for life (Ex. Oxygen)

• Results in the release of harmful chemicals (Ex. reactive oxygen species, enzymes), cause inflammation and damage to surrounding tissue

Apoptosis

• Carefully regulated process where the cell breaks down in a controlled manner

  • Body is able to dispose released cell components without inducing inflammation

• Occurs frequently in the natural developmental process- When a fetus loses webbing between fingers inside the womb

Cancer

The uncontrolled growth of abnormal cells in the body- A complex and diverse collection of different diseases

• Abnormal cell populations that divide uncontrollably and invade, potentially spreading to other tissues

Neoplasm

• Any abnormal tissue that forms when cells grow and divide more than they should 

  • Or when they do not die when they should

• Term can refer to harmless growths of cells (ex. skin tags), or cancerous growth
  

Tumour

• Non-specific term for a neoplasm 

• Word simply means “mass”- Any swelling or abnormal enlargement in or on body

• Can be harmless (Benign) or cancerous (malignant)

Metastasis

When malignant tumours spread to other areas of body

Spirituality in Learning- Indigenous Ontologies

A way of organizing information into categories and concepts

Spirituality in Learning- Knowledge Epistemologies

The philosophical theory of knowledge;

• How knowledge is validated and understood- What defines a justified belief vs an opinion

Carcinoma

• Type of cancer that affects Epithelial Cells (cells on surface of body)

• Usually in form of solid tumours

• Ex. Lung, Colorectal, & Breast Cancers

Sarcoma

• Begin in tissues that support and connect the body

• Can develop in fat, muscles, nerves, tendons, joints, blood vessels, lymph vessels, cartilage, or bone

Lymphoma

• Begins in the Lymphocytes

  • Lymphocytes- Infection fighting cells of immune system, found in glands, nodes, etc.

Glioma

• Tumours that arise from the connective tissues of brain

  • The cells that support the neurons of the brain

Leukemia

• Cancer of blood and bone marrow cells

• Occurs when healthy blood cells change and grow uncontrollably

Carcinogens

Risk factors for cancer

• Ex. Family history, tobacco, aging, UV radiation

Injury Hypothesis

1. Injury

2. Repair

3. Resting State

4. Persistent Activation

5. Cancer

Silent Mutation

A change in DNA sequence that doesn’t result in change of amino acid sequence, doesn’t affect protein product

Oncogenic Mutation

A mutation that directly contributes to development of cancer

Steps of Cancer Evolution

1. Transformation

2. Progression

3. Proliferation

4. Tumour Heterogeneity

Oncogenes

Mutated genes that lead to cancer

• Produce proteins with new or altered functions

Proto-Oncogenes

• Unmutated form of oncogenes

• Normal genes that are involved in cell growth and proliferation

Sporadic Cancers

Cancers in a patient with no clear family history of cancer

• Oncogenes commonly associated with this

Tumour Suppressor Genes

• Associated with preventing uncontrolled growth, inducing cell death

• Play role in developmental processes that require controlled apoptosis

• Both tumour suppressor alleles must be mutated in order to contribute to cancer progression

Familial Cancers

Cancer with a clear inherited component- Identified by family history or genetic testing

Two Hit Hypothesis

• Both cells tumour suppressor genes must be mutated in order for cell to become cancerous

• Most tumour suppressor genes need both alleles to be inactivated through mutations or epigenetic silencing- To cause a phenotypic change

• Children who inherit retinoblastoma (RB) are born with 1 mutation in a cancer susceptibility gene

  • Later acquire a 2nd mutation in the same gene

TP53?

Model Tumour Suppressor Gene

• Mutated in some capacity in nearly all cancers

Protein product of TP53?

p53- Regulates cell division

p53 Protein?

‘Guardian of the Genome’

• Coded by TP53 gene

• Role- Respond to genomic damage by activating repair and/or cell death programs

  • Preventing cells with cancer causing mutations from surviving

• Puts “breaks” on cells- So they don’t divide too fast

Senescence

State in which a cell has lost the ability to replicate

ERBB-1

‘Model Oncogene’

• Codes for protein Epidermal Growth Factor Receptor (EGFR)

Ligands

Extracellular signals

Tyrosine Kinase

An enzyme that can transfer a phosphate group to specific proteins inside a cell

• Functions as an "‘on’ or ‘off’ switch in many cellular functions

Mechanism of Action of EGFR

1. Ligand Binding

   • Intercellular domains undergo a structural change- Activating the receptor

2. Phosphorylation

   • Attachment of a phosphate group to another molecule in cytoplasm

3. Gene Expression

   • The signal has been transmitted to nucleus

   • Then increases transcription of genes involved in cell proliferation and survival

4. Termination

   • To terminate- Ligand is released OR receptor is broken down

Chemotherapy

• EGFR Cancer therapy

• Not targeting EGFR directly

• __ agents will kill any rapidly-dividing cells in the body

Antibodies

• EGFR Cancer therapy

• Specific __ produced outside body are injected

• Can cause inactivation and destruction of target protein OR cell death via immune system activation

Kinase Inhibitors

• EGFR Cancer therapy

• Small molecule __ can transverse the plasma membrane and disrupt signalling cascades