Intro To Patho Flashcards
Physiology
Study of functions of the body
Pathology
Study of structural/functional changes
Pathophysiology
Changes that occur with injury/disease
Disease
Interruption or disorder of body system(s)/organ structure(s)
- s/sx
- etiologic agents
Disorder
Abnormality of structure or function that has not been classified a “disease”
- commonly used interchangeably with “disease”
- applied to mental health conditions
Etiology
How a disease process is initiated or provoked
Ex: smoking is a cause of lung cancer
Idiopathic Etiology
Etiology is unknown
Iatrogenic Etiology
Unintentionally caused by a health care provider or institution
- medications, surgeries, other tx
Pathogenesis
The sequence of cellular/tissue/organs events that take place throughout the disease process
- evolve to show clinical manifestation
Clinical Manifestations
Evidences of disease
- Related to primary problem
OR
- The body’s attempt to compensate
Sign vs. Symptom
Sign
- Objective, observable; local vs. systemic
Symptom
- Subjective; complaints/concerns
- Comes from the patient
What are some examples of signs? (Clinical Manifestations)
- High HR upon auscultation
- ECG showing ST segment elevation
- Low BP
- Low BG level
What are some examples of symptoms? (Clinical Manifestations)
- Patient says they feel chest pain
- Patient feels their rapid heart rhythm and says “ I have palpitations”
Clinical Course
Evolution of the disease over time
- Acute vs. Chronic
- Exacerbation vs. Remission
- Prognosis —> likely outcome
Prognosis
Likely outcome of a disease
- part of its clinical course
Complication vs. Sequela(e)
Complication:
- disease or injury from the treatment of a preexisting disease/injury
Sequela(e):
- abnormal condition resulting from a disease or injury; neg consequence of a disease or injury
What are some examples of complications?
- Pt. develops a C.diff infection after being hospitalized for a r hip fx
What are some examples of sequela(e)?
- Patient w R hip fx develops a limp
- Diabetic pt develops CKD and neuropathy
- Diabetic pt has an episode of hypoglycemia
Epidemiology
Study of disease occurrence in populations
Incidence of a disease
Number of NEW cases in a population during a period of time
Prevalece
Measure of ALL the existing disease cases at a point in time
Morbidity
Diseased state
Mortality
Death
Homeostasis
Physiologic steady state; stable internal environment
Ideal set point —> pH, body temp
Allostasis
Dynamic process that maintains or re-establishes homeostasis or balance in response to stressors and changes in the environment
What does it mean that allostasis is an “adaptive process”?
The body’s original homeostatic set point may not always be possible achieve again, so the body sets a new homeostatic state
- example: COPD
What is a compensatory mechanism?
Physiologic changes initiated when the body is under stress
An attempt to maintain homeostasis
What happens if a compensatory mechanism remains chronically “turned on”?
May turn into a vulnerability
- Can kill you
Meant to be SHORT-TERM RESPONSES to a disturbance (crucial for trauma/acute illnesses)
Stress
Real or perceived threat to the balance of homeostasis
- biological vs. psychological
- acute vs. chronic
What two systems are involved in the body’s neurohormonal response to stress?
- Sympathetic Nervous System (epinephrine, norepinephrine)
- Hypothalamic-Pituitary-Adrenal (HPA) Axis (cortisol)
Why is an increase in blood glucose important during a significant stressor or trauma?
A rise in BG prepares the body to have enough energy to respond to the stressor or trauma
What is allostatic overload?
Widespread, multi-system effects of chronic stress
Hypertrophy
INCREASE in cell SIZE
- Triggered by mechanical and/or tropic signals
Atrophy
DECREASE in cell SIZE
- associated w damage or disuse
Hyperplasia
INCREASE in cell NUMBER
- incr. rate of cell division
Metaplasia
Replacement of a well-differentiated, mature cell with another well-differentiated cell type
- new type usually able to withstand the stressor better
Dysplasia
Deranged/disorderly cellular growth, with variations in size, shape and arrangements
- cells usually poorly differentiated
- may lead to cancer
Example of metaplasia: Lung epithelium in smokers
Cell type changes from columnar cells to squamous cells that can better tolerate the repeated stress of the cigarette smoke
Eventually, though, cells may become dysplastic
Ischemia and Infarction - cell injury
Decrease in ATP | Multiple downstream effects
- cell swelling, death
- inability to power key functions (NA/K pump)
Direct chemical or radiation damage to DNA
Leakage of pro-apostolic proteins
- Decreased ATP
- cell death
Increased calcium entry into cells - cell injury
Entry of Ca2+
- Increase mitochondrial permeability
- Activation of multiple cellular enzymes
- Enzymes degrade cell membranes, proteins, DNA
- Accumulation of intracelular Ca++ will cause cell death
Generation of ROS (reactive oxygen species) - cell injury
Increase ROS
- Damage to lipids, proteins, DNA
- ROS are extremely damaging to cells
Direct injury to cell membranes, lack of membrane integrity due to loss of ATP - cell injury
Damage to plasma membrane
- loss of cellular components
Damage to lysosomal membrane
- enzymatic digestion of cellular components
We can measure incr cellular components in pt.’s serum levels
- cells burst and release their contents into the bloodstream
Injury from radiation, chemicals, toxins, pH changes, ROS - cell injury
Protein misfolding, DNA damage
- activation of pro-apoptosis proteins
- cell death
- misfolded proteins cannot carry out their functions
Inflammation - cell injury
Critically important response to injury
Very common response
When chronic, can cause significant cellular/tissue injury
- fibrosis, scarring
- generation of ROS
- infiltration by WBCs, constant cell signaling leading to more inflammation
Ischemia
Interruption of blood flow
- blood clot blocking a vessel
- blood vessel compression
Ischemia cell death most commonly affects the heart (myocardial infarction) or brain (stroke)
- can also occur in the periphery, kidneys, liver, gut, and other tissues
What deficits lead to the manifestations of ischemia?
Hypoxia (lack of tissue oxygen)
- compromises ATP production
- leads profound energy deficit for cell functions
Lack of blood flow
- buildup of waste products that are not removed
- loss of constant energy supply to tissues in the form of glucose and other metabolic substrates
What is the major downstream effect of ischemia?
Decreased ATP production
- leads to dysfunction of Na/K pump (disrupts ionic homeostasis and cell integrity)
- increases anaerobic glycolysis
- causes detachment of ribosomes from the endoplasmic reticulum
How do pressure ulcers lead to ischemia?
Sustained pressure over a bony prominence leads to compression of blood vessels, ischemia, and ultimately tissue necrosis (death)
- immobile pts at higher risk of dev pressure ulcer
- also can be due to medical devices being left in place for an extended period of time
What is infarction?
The permanent (irreversible) loss (death) of cells caused by an extended period of ischemia
What are ROS - reactive oxygen species?
- Radicals like hydroxyl radical (OH most reactive ROS of all)
- contain an atom that has an unpaired electron in its outermost shell. Highly unstable configuration
- Molecules Ike hydrogen peroxide H2O2
- Ions like hypochlorite ion OCI-
- Molecules which are both ion and radical like superoxide anion O2-
What is Glutathione (GSH) and what does it do?
An important antioxidant and free radical scavenger
- converts hydrogen peroxide to 2 molecules of water
- Certain disease states may result from insufficient glutathione
How are ROS neutralized?
Under normal, healthy conditions, ROS produced by mitochondria are neutralized by enzymes and peptides that convert them to non-toxic molecules
Example: Glutathione (GSH)
Which organelles are more likely to initiate apoptosis?
Rough ER
Mitochondria
REVIEW: Rough ER
- Protein Synthesis
- Quality control: misfolding detected —> STOP transcription and translation, incr production of chaperone proteins to fix problem
- Can initiate apoptosis if unfolded proteins accumulate and cause excessive ER stress
REVIEW: Smooth ER
- Maintains homeostasis
- Metabolic enzymes synthesize hormones and lipids, degrade drugs and other biochemicals
- The ER membrane calcium ATPase maintains normal low levels of intracelular calcium
REVIEW: Mitochondria
- ATP production
- Calcium storage (similar to smooth ER)
- When damaged, causes outer mitochondrial membrane leak, proteins such as cytochrome C enter cytoplasm and signal for apoptotic pathway of cell death
Cell injury that damages mitochondria or disrupts rough ER synthesis results in….
Cell apoptosis
Apoptosis Purposes
Tightly regulated cell “death program” - normal process for the most part
- Balances cell division (otherwise the tissue would grow or shrink)
- Destroys damaged or infected cells (immune system)
- Protects against dev of cancer (cancer cells can evade apoptosis)
Extrinsic signs for apoptosis
Coming from outside the cell
- absence of a “survival” signal from neighboring cells or ECM
- presence of a “death” signal involving activation of “death receptors” (TNF receptors)
Intrinsic signs for apoptosis
Coming from inside the cells; initiated by mitochondrial or ER stress
- Cell injury
- Growth factor withdrawal
- DNA damage (by radiation, toxins, free radicals)
- Proteins misfolding (ER stress)
How do intrinsic and extrinsic signals cause apoptosis?
- Activate enzymes called capases that begin a cascade
- Cell shrinks and condenses, cytoskeleton collapses, nuclear envelope disassembles, nuclear DNA breaks up into fragments
- Apoptotic bodies form
- Cell surface is changed, exposing molecules that cause dying cell to be rapidly phagocytosed (by a neighboring r macrophage cell, before leakage of cellular contents occurs)
Necrosis results in:
- Induces inflammation (w associated pain, swelling) that perpetuates tissue damage
- May damage neighboring tissue
- Membrane swelling, rupture, and cellular dissolution; with leakage of cellular contents
- Messy, disorganized process
Feature of necrosis and apoptosis
*Cell size
*Nucleus
*Cellular contents
*Adjacent information
*Physiologic or pathological role
On slide 81
Cell size
- Swell vs. shrink
Nucleus
- disrupted vs. intact
Cellular contents
- leak into blood stream vs. released in apoptotic bodies, phagocytosed
Adjacent information
- frequent (leading to swelling + pain) vs. none
Physiologic or pathological role
- invariably pathological vs. often physiologic
Autophagy Purposes
“Self-eating” primarily through lysosomal mechanism - also tightly regulated process
- Removes and/or recycles protein aggregated and damaged organelles
-promotes cell survival and tissue homeostasis
Possibly triggered by cellular nutrient depletion/deprivation —> increases during fasting
Also seen in degenerative diseases
What key substances cannot be produced by mitochondria in regions of ischemia or infarcted tissue?
ATP
Answer after lecture
What key cellular functions are disrupted when ATP cannot be produced?
Na/K pump —> ionic imbalance
Build up of waste products
Increase in blood glucose
