1
Q
Define disease, anatomic and clinical pathology, idiopathic, iatrogenic, prevalence, and incidence
A
- Disease: a change from homeostasis
- Pathology: The study of changes in bodily structure and function that occurs as a result of disease
- Anatomic pathology: The study of structural changes caused by disease
- clinical pathology;
The study of the functional aspects of disease by laboratory study of tissue, blood, urine or other bodily fluids - Idiopathic: Unknown etiology (don’t know what caused it or where it comes from)
- Iatrogenic: If the disease is a by-product of treatment or diagnosis, Physician caused
- Prevalence: The number of people who have the disease at any given moment in time
- Incidence: The number of new cases of the diseases per year
2
Q
Differentiate between signs, symptoms and syndromes
A
- Sign: A direct observation by examiner
- Symptom: A complaint reported by the patient
- Syndrome : A collection of sings, symptoms along with data to support (evidence based) specific to a condition or disease
3
Q
Articulate the relationship between health, sick, normal and abnormal
A
- Normal vs abnormal describe results of measurements that are used to know if a patient has a disease or not
- Sick is the presence of disease while healthy is the absence of disease
- To see if a patient is healthy or sick we use results that are normal or abnormal to tell us this
4
Q
Explain the differences among true positive, false positive, true negative and false negative tests
A
- True negative: the patient is healthy and tests normal
- False negative: the patient is sick and tests normal
- True positive: the patient is sick and tests abnormal
- False positive: the patient is healthy and tests abnormal
5
Q
Explain the meaning of normal range as it relates to medical tests
A
- Normal range is seen in 95% of healthy individuals and is Determined from a sample of people without disease
- The normal range is used to depict if a patient is healthy and within normal limits or if they are sick and have an abnormal result
6
Q
Articulate the relationship between specificity and sensitivity
A
- Sensitivity: The ability of a test to be positive in the presence of disease or the true positive rate
- Specificity: The ability of a test to be negative in the absence of the disease or the true negative rate
- A test can not be both but rather a highly sensitive test will be used first to ensure that it misses very few that have the disease and then a specific test will differentiate between true positives and false positives in the absence of disease
7
Q
Articulate how diffusion, osmosis and active transport maintain cellular homeostasis
A
- For a cell to survive it needs to obtain and use energy, make new cells, exchange materials and eliminate waste
- These types of transport allow the cell to maintain homeostasis (maintenance of a confstant internal state in a changing environment
- Diffusion maintains it by allowing cellular food to diffuse into the cell while waste can diffuse out of the cell
- Osmosis maintains it through the diffusion of water to maintain a specific water balance which is needed for chemical reactions ( it balances out other molecules)
- Active transport maintains it by allowing materials into the cell that have a higher concentration within
8
Q
Define and differentiate between the adaptations of cells to changing conditions with an example
A
- Atrophy: a reduction in the size of cells in response to diminished function ( after wearing a cast muscle gets smaller)
- Hypertrophy: the increase in size of each cell without an increase in number of cells ( muscles getting bigger when weightlifting)
- Hyperplasia: the increase in size of a tissue or organ caused by an increase in number of cells (BPH: benign prostatic hyperplasia)
- Metaplasia: A change from one type of cell to another that can tolerate a new environment (within smokers the ciliated columnar lining of trachea turns to squamous epithelium)
- Dysplasia: the development and maturation of cells that are disturbed and abnormal ( chronic irritation or inflammation and can progress to neoplasia: formation of tumor)
- Increased enzyme synthesis: a response to increased demand of cell to synthesize more enzyme s from Smooth endoplasmic reticulum (alcoholics produce more enzymes to metabolism alcohol in order to eliminate it faster
9
Q
Evaluate the significance of cellular injury, necrosis, apoptosis and aging in the cell
A
- Cell injury: when the cell is injured and if normal cell function returns it can be reversed but if does not recover then necrosis can occur, two types is cell swelling and steatosis which cause changes in the structure of the cell (alters normal cell function)
- Cell swelling: occurs when the transport mechanism fails in the cell which causes sodium to be in high levels within the cell and water then follows (can be reversed if energy production continues: allows sodium to be transported out of the cell and thus water follows) if swelling continues hydropic swelling results (accumulation of fluid filled vacuoles)
- Steatosis: cell injury through fatty change. Within normal cells fat is metabolized and exported but within steatosis these enzyme systems are impaired which leads to the accumulation of fat droplets within the cytoplasm (common in liver)
- Necrosis: cell death
- Apoptosis: programmed cell death, is normal and if doesn’t happen when it should disease can occur.
- Cell aging: all cells age then die (stem cells don’t, some cancer also) normal cells die when the hayflick limit is reached (the fixed number of divisions that normal cells undergo before they die). However cells age differently (neurons cant divide, organs that divide constantly are prone to cancer and enzyme systems become less active when older
10
Q
Define hematopoiesis, phagocyte, antigen, pathogen
A
- Hematopoiesis: When blood cells are exposed to cytokines and surrounding stromal cells they differentiate into Megakaryocytes (thrombocytes: platelets), Erythrocytes (red blood cells), Leukocytes (white blood cells)
- Phagocyte: a type of cell within the body capable of engulfing and absorbing bacteria or other things
- Antigen: a molecule or structure that can bind to a specific antibody or t-cell receptor, the presence of antigens within the body can trigger an immune response
- Pathogen: any organism or agent that can produce disease
11
Q
Compare and contrast innate and adaptive immunity in how they fight disease
A
- Innate immunity: refers to the host defense mechanisms that are immediately available on exposure to pathogens because they are always present, Includes epithelial barriers, mucous membranes
Cells within the innate immune system are granulocytes, mononuclear phagocytes, natural killer cells, dendritic cells- Adaptive immune system: Characterized by antigen specificity and immunological memory, More complex process as requires antigen processing and recognition, Takes days to develop a response
Cells within this are B and T cells
- Adaptive immune system: Characterized by antigen specificity and immunological memory, More complex process as requires antigen processing and recognition, Takes days to develop a response
12
Q
Identify and describe the functions of the main cells of innate and adaptive immune systems
A
- Innate cells
- Granulocytes: Neutrophils, eosinophils, basophils, mast cells, Often the first cells to arrive at the site of injury, Characterized by granules in their cytoplasm and their varying shapes of the nucleus, Engulf and kill pathogens in their cytoplasmic granules to kill the pathogen and also enhance inflammatory response
- Mononuclear phagocytes: Monocytes and macrophages, Monocytes are baby macrophages, Monocytes circulate in the blood and when they go into tissue they can grow 5-10x into macrophages, Remain motile and reside in reticular connective tissue, Also release pro inflammatory molecules like cytokines or eicosanoids
- Natural Killer cells: Cytotoxic lymphocytes that target tumour and virus infected cells not a specific(check other white blood cells to see if they are damaged or infected), Selectively pick damaged or infected host cells as there is an abnormal expression of surface molecules on damaged cells
- Dendritic cells: Connection between innate and adaptive immunity, Reside in tissues and stimulate adaptive immune response, Immature ones patrol peripheral tissues and capture pathogens through phagocytosis, Mature ones then migrate to the lymphoid organs to present the antigens they discovered to the T-cells
2. Adaptive cells - B cells: A naïve b cell encounters a pathogen ad binds to it through immunoglobin (b cell receptor), The B cell multiplies, Its offspring differentiate into plasma cells or memory cell cells (guided by interleukins
Plasma cells: short lived and secrete antibodies
Memory B cells: long lived and express the same immunoglobin as the parent cell, responsible for a quick secondary response when coming into contact with the same pathogen - T Cells: Express receptors that only recognize antigens that are expressed by the dendritic cells or other antigen presenting cells (memory B cells)Three types: Tc, Th, Memory T cells
Tc cells: destroy host cells that are infected
Th cells: secrete cytokines that enhance the function of other cells to help in getting rid of pathogens
Memory T cells: can persist for years and mount a quick response on re exposure
13
Q
Outline the lymphatic system and lymphatic recirculation
A
- The lymphatic system is a network of lymphatic vessels connected to lymph nodes
- It collects plasma continuously leaking out from blood vessels into the interstitial space and returns the fluid (lymph) to the blood
- Only flows upwards to the neck with rhythmic contractions of smooth muscle
- Primary lymphoid organs (bone marrow and thymus) are responsible for lymphocyte maturation and development, while secondary are where mature lymphocytes interact with antigen presenting cells
- Lymphatic recirculation:
1. B and T cell development in bone marrow and thymus enter blood stream
2. When they reach a secondary lymphoid order they enter it
a) If antigen is detected: stays in the tissue and becomes activated
b) No antigen detected: exits through lymph and re enters bloodstream
3. Allows continuous monitoring of the secondary lymphoid organs for infection
14
Q
Summarize how knowledge of the immune system is vital to effective treatment
A
- Pathophysiology and pharmacology are connected as Many different infections or diseases will all have anti inflammatory and sometimes immuno-suppressants in treatment
15
Q
Briefly explain the mechanisms of action of drugs affecting immunity
A
- MOA: the process by which a molecule such as a drug functions to produce a pharmacological effect
- Bactericidal: drugs that kill/ destroy bacteria by themselves
- Bacteriostatic: drugs that slow down the growth of bacteria and need bodies immune system to dispose of bacteria
- Penicillin’s: also know as beta lactams
Disrupt bacterial cell walls as bacteria have penicillin binding proteins which the beta lactam ring can bind to which weakens the cell wall and allows fluid to enter and destroy it
If bacteria have a beta lactamase (breaks the beta lactam ring) we can add other drugs such as clavulanic acid which inhibits B-lactamases - Cyclosporine: inhibits production and release of interleukin II (promotes development of immune cells) and inhibits interleukin II induced activation resting T-lymphocytes
Suppresses entire immune system (not specific) - Methotrexate: inhibits DNA synthesis, repair and cellular replication by inhibiting dihydrofolate reductase inhibiting the formation of reduced folates, and thymidylate synthetase, resulting in inhibition of purine and thymidylic acid synthesis, thus interfering with DNA synthesis, repair and cellular replication; it is cell cycle specific for the S phase of the cycle
Good against actively proliferating cells - Antihistamines: block histamine receptor to provide relief against allergic rhinitis
16
Q
Articulate the purpose of inflammation
A
- Inflammation is a physiological response to infection or tissue injury
- Restricts damage to the localize site, recruits immune cells to kill pathogens, start wound repair
- Signs are pain, heat, redness, swelling
17
Q
Analyze and justify each symptom of the acute inflammatory response
A
- Heat: capillary dilatation-> increased blood flow
- Redness: increased capillary permeability-> extravasation of fluids
- Swelling: Attraction of leukocytes-> migration of white cells to site of injury
- Pain: systematic response-> fever and leukocytosis
18
Q
Define and discuss diapedesis
A
- The movement of leukocytes out of blood into the site of infection or tissue damage
- Chemoattraction: various inflammation mediators (cytokines, histamine, prostaglandins, leukotrienes) are released
- Rolling adhesion: carb chains on the surface of the neutrophil cause leukocytes to roll on the edge of the blood vessels rather then middle
- Tight adhesions: multiple cytokine and integrin receptors (depends on location)
- Transmigration: the leukocytes try to squeeze past the blood vessels
19
Q
Outline the consequences of chronic inflammation
A
- Chronic inflammation: a result from continuous exposure to offender
- The accumulation and activation of macrophages and lymphocytes as well as fibroblasts (fibrosis: excessive fibrous connected tissue that interferes with normal tissue function) that replace the original, damaged or necrotic tissue
- The inflammation has now lost its helpfulness and we need to now use pharmacotherapy and involve anti inflammatory
20
Q
Evaluate inflammatory mediators and their specific roles in inflammation
A
- Cytokines: soluble factors secreted by immune cells that are activated, four groups
- 1: promote inflammation and mediate natural immunity (recruit more cells to area, so can inhibit this group to stop some inflammation)IL-1, IL-6, IL-8, TNF, IFN-a
- 2: support allergic inflammation (IL-4, IL-5, IL-13)
- 3: immunoregulatory activity (slow it all down, recruited late on and clean everything up after its all done, can use drugs to boost these to reduce inflammation) IL-10, IL-12, ITGF-B, IFN-y
- 4: act as hematopoietic growth factors (tell us to get more cells, drugs can be used to affect this so it increase the amount of cells generated)
IL-3, IL-7, GM-CSF
2. Histamines: A bioactive amine which is packaged into dense intracellular granules, Mast cells are famous for releasing it, When histamine is released it binds to histamine receptors - H1: within smooth muscle of the vascular system, bronchial tree, digestive track and nasal glands
Causes allergies, allergic reactions - H2: lining of stomach and produces gastric acid
Blocking these reduced the amount of acidity within the stomach - H3: within the CNS and involved in releasing neurotransmitters such as dopamine, GABA, acetylcholine, noradrenaline, serotonin
There is no way of blocking these as of now
3. Prostaglandins: Generated from arachidonic acid through the cyclooxygenase pathway, Have many functions including constrict/ dilate vascular smooth muscle cells, cause aggregation/ disaggregation of platelets, induce labour, release during menstruation, play an important role in mucosal production in Gi tract, act on thermoregulatory centre to produce fever - The enzyme that converts arachidonic acid to prostaglandins is COX
4. Leukotrienes: Generated from arachidonic acid through the lipoxygenase pathway, mostly active in smooth muscle lining of the bronchioles, Contribute significantly to the pathophysiology of asthma - Contributes to asthma through airflow obstruction, increased secretion of mucous, bronchoconstriction, infiltration of inflammatory cells in airway
5. Cortisol: A hormone released in response to stress, Job is to return body back to homeostasis - Two main effects are anti inflammatory and immunosuppressive and has receptors throughout the body
- anti-inflammatory MOA: Decrease production of phospholipase A, this decreases production of prostaglandins, leukotrienes, thromboxane’s, Decreased leukocytes means less recruitment of leukocytes to site of injury, Decreased bactericidal activity of phagocytes and stabilizes mast cells
-immunosuppressant MOA: Induce apoptosis of T cells, This means less T cell recruitment to site of antigen, This increases T cell redistribution to lymph nodes and there is no B cell effects from cortisol
21
Q
Articulate the mechanisms of action of drugs affecting inflammation
A
- Biologics (cytokines): drugs that are used using biological processes
- Can use antibodies to target:
- Monoclonal antibodies can use antibodies to targe specific receptors or pathogens
- Can attach a drug to an antibody which allows the antibody to only target specific cells and thus the drug only targets those specific cells
- This can make therapy more effective and minimize adverse effects
2. Antihistamines (histamine): two types but both block H1 receptors - 1st: block H1 receptors, shorter acting, cause drowsiness, work faster, usually used to treat allergic response
- 2nd: longer acting, less sedating, take longer to start working, can be used everyday
3. NSAIDs (prostaglandin): Inhibit cyclooxygenase (COX), This reduces prostaglandin synthesis which then inhibits inflammation , Have analgesic and antipyretic properties, Can be used to treat mild to moderate inflammation, fever, dysmenorrhea (period cramps), platelet inhibition - Classic NSAIDs: inhibit both COX-1, and COX-2
Ibuprofen, naproxen - COX-2 inhibitors: more specific to inflamed tissue
4. Montelukast (Leukotrienes) - Leukotriene receptor antagonists (LTRAs)
- Reduces inflammation by blocking leukotriene receptors
- Is preventative and doesn’t work fast enough for immediate relief
- Adverse effects include headache, cough GI upset
- Must be taken daily to work
5. Corticosteroids (cortisol): - It is a synthetic version of cortisol (mimic human endogenous cortisol)
- Has many different uses such as asthma or allergies
- Three types: Short acting: hydrocortisone, cortisone/ Intermediate acting corticosteroids: methylprednisolone, prednisone/ Long acting corticosteroids: betamethasone, budesonide
22
Q
Describe the factors of complexity of understanding drug classification
A
- Large volume of drugs: these is over 10,000 agents available
- Each drug within the specific class has distinct characteristics
- Each drug can have more than one indication and mechanism
- They may have different responses depended on individual factors
- Lack of consistency between classification, professions, languages…
23
Q
Analyze a drugs chemical name, generic name, and trade name and give examples of each
A
- Chemical name: a direct description of the chemical structure
NaCl- Generic name: the unique name that is given to chemical structures that somewhat describes the structure
Ibuprofen - Brand/ trade name: the marketed name given to a drug
Advil
- Generic name: the unique name that is given to chemical structures that somewhat describes the structure
24
Q
Explain why it is safest practice to use generic names in practice
A
- It reduces errors
- Stays the same across languages
25
Outline the key Canadian governance structure and drug regulations
- Narcotic control regulations
- Controlled drugs and substances act
- Food and drugs act and regulations
26
Describe how drugs are classified and regulated by the government in Canada
- Federal control: controlled substances (narcotics)
- Provincial control: all other drugs including Rx, OTC, NHPs (schedule I,II, III or unscheduled)
27
Differentiate between therapeutic, pharmacological and family classification of drugs and recognize examples of each
1. therapeutic classification
- Organizing drugs based on their therapeutic usefulness in treating a particular disease
- Example is anti inflammatory (reduce inflammation)
2. Pharmacological classification
- Organizes drugs based on the way a drug works at a molecular level, tissue and body system level
- Example: calcium channel blocker (blocks calcium channels)
- Addresses a drugs mechanism of action
3. Family classification
- Organizing drugs according to its chemical structure in some way
- Corticosteroids (contain the ring structure)
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