Pathological Analysis
Describe the key differences between a cytological specimen and a tissue biopsy and discuss the inherent strengths and limitations of each.
Cytological specimens-Full thickness of cell
Biopsies-Cells within anatomical context
Explain the relationship among data, information and knowledge.
Data: symbols that represent observations
Info: Data + meaning (who, what, when, where)
Knowledge: application of info to answer the "how"
Discuss the following key principles of medical ethics:autonomy, beneficence, non-maleficence, and justice.
General beneficence - broad ideal actions
Specific beneficence - obligatory actions, relationship
Describe cellular, humoral, and innate immunity testing
Cell: normal t cell count (WBC, differential, FLOW), subset (FLOW), and function (DTH)
Humoral: normal b count (CBC, FLOW), level of antibody (Serum electrophoresis, quantitative Ig), diversity of antibody, specificity (ELISA, ANA -indirect immunofluorecence)
Innate:NBT, neutrophils stimulated to produce ROS (normal blue)
Define physiologic homeostasis and adaptation to stress.
1. Homeostasis: maintaining a healthy state
2. Adaption: reversible functional and structural responses to changes in physiological states
a. Hypertrophy: increase in size
b. Hyperplasia: increase in cell number
c. Atrophy: decrease in size and metabolic activity
d. Metaplasia: change in cell phenotype
Describe the different types of cytological procedures and tissue biopsies and explain how they are used in the clinical setting.
Illustrate how data, information and knowledge are used in complex systems, using lab testing examples.
Hgb concentration -> low or high values -> pts with low hgb benefit from RBC transfusion
Describe the prerequisite conditions for autonomous decisions, including liberty and agency.
Liberty: freedom from controlling influence
Agency: capacity for intentional action -State a preference, understand information, reason through life decision
FLOW
Can use to sort based on protein they express
Define cell injury and list at least seven potential etiologies
1. Hypoxia
2. Physical agents
3. Chemical agents and drugs
4. Infectious agents
5. Immunological reactions
6. Genetic abnormalities
7. Nutritional imbalances
Describe the inherent trade-offs between small versus large biopsies, and the relationship between biopsy size and sampling error
Sampling error: influenced by how uniform the tissue (Diffuse or Multifocal or focal (can miss, yield proportion to biopsy size))
Describe the lab test lifecycle from order to result to action with relevant information systems at each step.
Pt goes to doctor (appointment) -> dr orders lab test (Computerized order entry: CPOE)-> sample is taken (positive patient identification: PPI) -> sample sent to lab (specimen tracking/barcode) -> test analyze sample and produce results (laboratory information system: LIS)-> clinical lab provide results to dr (EHR) -> dr interprets results -> dr tells pt of results (patient portal) -> dx and treatment decided by pt and dr -> pt goes to dr (repeat cycle)
ELISA (sandwich and antigen specific)
Describe the major determinants of the cellular response to injury and list the principal biochemical mechanisms.
1. Consequence depends of the state, type and adaptability of cell
2. Mitochondrial damage:
a. Decreased production of ATP
i. Loss of mem pump activity -> swelling
ii. Increased glycolysis -> lactic acid -> low pH -> low enzyme activity
iii. Decrease protein synthesis
iv. Increase cytosolic Ca++ -> mitochondria mem damage -> necrosis
v. Opening of mitochondrial permeability pore -> decrease ATP -> necrosis
b. More ROS
c. Initiation of apoptosis or necrosis
3. Membrane damage
a. Loss of osmotic balance -> swelling
b. Detachment of ribosome -> Disruption of protein synthesis and secretion via effects on ER and golgi
c. Release of lysosomal enzymes with cell death
d. Increased Ca++, activation of enzymes -> cytoskeletal abnormalities
e. Damage to mitochondrial function with decreased ATP
f. ROS -> injury via lipid peroxidation
g. Increased phospholipid breakdown, decreased synthesis
Describe what is meant by an "adequate" versus an "inadequate" biopsy.
List human and systems causes of medical errors in non-healthcare and healthcare settings.
Person: forget, in attentive, carelessness
System: work conditions and procedures, lack of redundancies, system defenses failed
Evaluation of complement
CH50 assay: Sheep RBC coated with rabbit antibodies. If patient compliment work then RBC lysis
Describe the morphological features of reversible versus irreversible or progressive cell injury.
1. Reversible: swelling, fatty change (triglyceride filled vacuoles) myelin figure membrane blebs
2. Progressive injury: breakdown of plasma mem, organelles, and nuc, leakage of contents
3. Irreversible: inability to reverse mitochondrial dysfunction, profound disturbance in membrane function
List four potential adverse consequences of tissue biopsies.
Bleeding
Reactive changes (e.g., scarring)
Infection
Delayed healing
In some settings, perforation of a viscus, duct, or organ; or collapse of a lung
Define latent and active failures
Active = human factors (at the bedside)
Latent = systemic (away from the bed side ie equipment)
Necrosis v Apoptosis v other cell death
2. Necrosis
a. Swelling, disruption of plasma mem, nuclear lysis (karyolysis), contiguous group of cells, inflammation
b. Caused by ischemia, chemical or microbial toxins, burn
3. Apoptosis
a. Shrinkage, intact mem, nuclear fragments, chromatin condensation, apoptotic bodies, single cells, no inflammation
b. Caused by dna damage, misfolded proteins and viral infection
4. Necroptosis
a. Hybird
b. Loss of ATP, swelling, ROS, lysosomal enzyme -> rupture
c. Triggered by singnal transduction pathway like apoptosis but no caspase, TNFR1, RIPK1 and 3
5. Pyroptosis:
a. IL1, inflammasome, fever
6. Ferroptosis
a. Cell death with more iron or ROS -> lipid peroxidation