Cellular Reaction to Injury Overview and Adaptations Flashcards
what are the 2 major categories of etiological factors
- genetic
2. acquired (environmental, infectious, something exposed to)
most illnesses have a —- etiology
multifactoral
pathogenesis
- succession of events in response to causative agent
- molecular and morphologic changes
clinical manifestations
- functional consequence of tissue alterations
- signs and symptoms (clinical diagnosis)
- clinical course and outcome (progress)
in response to harm the cell may undergo
- adaptive changes
a. reversible changes –> new steady-state - cell injury
a. reversible
b. irreversible
in response to harm the cell may undergo adaptive changes such as
- hypertrophy (size)
- hyperplasia (number)
- metaplasia (type - cell changes phenotype)
- atrophy (size and function - cell becomes smaller and function is not as necessary)
are adaptive changes reversible
YES!
reversible changes –> new steady state
what is hypertrophy
-increase in the SIZE of individual cells within an organ (same number of cells but larger, leading to larger organ)
hypertrophy results from an increased production of
cellular proteins (growth factors) generally triggered by an increase in workload (STRESS)
hypertrophy is mostly seen in what type of cells
non-dividing cells (ie. heart)
in most other organs hypertrophy co-exists with
hyperplasia
hypertrophy can be — and —
physiologic or pathologic
hypertrophy is caused by
functional (workload) or hormonal (growth factor)
examples of functional (workload) or hormonal (growth factors)
Myocardium
Uterus
Skeletal muscle
Mammary glands (puberty)
PHYSIOLOGY of myocardial hypertrophy occurs due to
- exercise (also pregnancy) leading to an increase in the heart’s muscle mass and pumping ability
- this type of hypertrophy is reversible (ie. after giving birth HR goes back to steady state)
PATHOLOGY of myocardial hypertrophy
- chronic hemodynamic overload (hypertension, vascular disease) leads to an increase in muscle mass
- the heart attempts to increase its pumping ability, often enlargement cannot compensate increased burden leading to injury
is hypertrophy a fast or slow process
slow
increase in cell size results from what
increase protein production and # of myofilaments increase myocyte force and work capacity of the heart
mechanisms of hypertrophy
- mechanical stretch (increased work load)
- agonists (eg. adrenergic hormones, angiotensin)
- growth factors (eg. IGF-1)
treatment with barbiturates leads to
hypertrophy of the SER in hepatocytes
barbiturates increase the amount of what enzyme
cytochrome P450 in the liver to detoxify the drugs (catalyzes metabolism of drugs via oxidation)
progressively what will happen in cytochrome P450 is increased in the liver
the pt will respond less to the drug bc of adaptation (catalyzes and metabolizes the drug via oxidation)
normal genetic variations (polymorphisms) in P-450 lead to what
different levels of activity and sensitivity to drugs in pts
what is hyperplasia
increase in the # of cells that make up the tissue/organ
hyperplasia can be — or —
hormonal or compensatory
hyperplasia often occurs with what
hypertrophy
what is hormonal hyperplasia
hormones/growth factors stimulating cells leading to increase in the functional capacity of the tissue/organ
what is mammary gland hyperplasia/hypertrophy (puberty/pregnancy)
increased proliferation of the glandular epithelium in the female breast leading also to increase in size of cells
when does compensatory hyperplasia occur
when an organ that has regenerative capability increases the # of cells to compensate for loss of mass
example of compensatory hyperplasia
liver regeneration in donors - following partial hepatectomy, remaining liver cells proliferate to regain original size and function
what is pathologic hormonal hyperplasia
-results from excessive hormonal stimuli to target cells
over stimulation and excess proliferation of cells can allow for
mutations to occur that can lead clonal formation and development of cancer
patients with certain types of hyperplasias can have
an increased risk for developing cancer
describe how the prostatic gland can undergo pathologic hormonal hyperplasia
under excess adrogenic stimulation, prostatic glands undergo hyperplasia leading to enlargement of the prostatic gland
characteristics of atrophy
- reduced organelles
- reduced metabolic need
- decreased in cell size
- decrease in # of cells
- decreased in organ size
- decrease in function of tissue
main causes of atrophy
- disease
- denervation
- decreased blood supply
- malnutrition
- hormonal under-stimulation
what is atrophy
- an adaptation to changes in steady-state
- cell decreases in size and organelles, reducing its metabolic needs to adapt to the change
atrophy: disure/inability to use
- skeletal muscle and bone can become atrophic if not used (ie. immobilized pt or post fracture)
- in some cases, is reversible to normal state if activity is resumed
atrophy: denervation
loss of nerve supply leads to loss of normal skeletal muscle function
atrophy: decreased blood supply (schema/compression)
decrease in blood flow secondary to atherosclerosis will lead to senile atrophy
atrophy: malnutrition
consumption of muscle as source of energy in malnourished pt leads to muscle wasting (cachexia)
atrophy: hormonal under-stimulation
female reproductive organs become atrophied in absence of hormonal stimulation
mechanism of atrophy
- decrease in cell # = apoptosis
- decreased in cell size (decreased protein synthesis, increased protein degradation)
what are 2 protein degradation pathways that occurs with atrophy
- ubiquitin degradation pathway - protein that needs to be degraded is tagged or ubiquinated
- autophagy - cell will autodigest some of its own components
what is metaplasia
change in phenotype (morphologic and functional type of a cell)
why do phenotypic changes of a fully differentiated cell occur
to better endure the stressful envrionment
is metaplasia reversible or reversible
reversible
what is the most common type of metaplasia
columnar –> squamous
Can be seen in respiratory, salivary, pancreatic, cervical, glands, etc.
if stress continues what happens to the metaplasia
metaplasia –> dysplasia –> cancer
vitamin A deficiency can lead to
- squamous metaplasia
- deficiency due to general malnutrition or any condition with fat malabsorption
what is vitamin A need for
- differentiation of specialized epithelium
- ocular conjunctiva (lacrimal/mucus secreting epithelium)
- upper respiratory passage (musociliary epithelium)
- urinary tract (transitional epithelium)
what is the mechanism of metaplasia
- the change in phenotype occurs through the reprogramming of stem cells that have the ability to differentiate through a different cell pathway
- this occurs via cytokines and growth factors stimulating expression of proteins that will drive cells toward a specific differentiation
