Cellular Reaction to Injury Overview and Adaptations

Question 1

what are the 2 major categories of etiological factors

Answer 1

1. genetic

2. acquired (environmental, infectious, something exposed to)

Question 2

most illnesses have a —- etiology

Answer 2

multifactoral

Question 3

pathogenesis

Answer 3

• succession of events in response to causative agent

- molecular and morphologic changes

Question 4

clinical manifestations

Answer 4

• functional consequence of tissue alterations
• signs and symptoms (clinical diagnosis)
• clinical course and outcome (progress)

Question 5

in response to harm the cell may undergo

Answer 5

1. adaptive changes
   a. reversible changes –> new steady-state
2. cell injury
   a. reversible
   b. irreversible

Question 6

in response to harm the cell may undergo adaptive changes such as

Answer 6

1. hypertrophy (size)
2. hyperplasia (number)
3. metaplasia (type - cell changes phenotype)
4. atrophy (size and function - cell becomes smaller and function is not as necessary)

Question 7

are adaptive changes reversible

Answer 7

YES!

reversible changes –> new steady state

Question 8

what is hypertrophy

Answer 8

-increase in the SIZE of individual cells within an organ (same number of cells but larger, leading to larger organ)

Question 9

hypertrophy results from an increased production of

Answer 9

cellular proteins (growth factors) generally triggered by an increase in workload (STRESS)

Question 10

hypertrophy is mostly seen in what type of cells

Answer 10

non-dividing cells (ie. heart)

Question 11

in most other organs hypertrophy co-exists with

Answer 11

hyperplasia

Question 12

hypertrophy can be — and —

Answer 12

physiologic or pathologic

Question 13

hypertrophy is caused by

Answer 13

functional (workload) or hormonal (growth factor)

Question 14

examples of functional (workload) or hormonal (growth factors)

Answer 14

Myocardium
Uterus
Skeletal muscle
Mammary glands (puberty)

Question 15

PHYSIOLOGY of myocardial hypertrophy occurs due to

Answer 15

• 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)

Question 16

PATHOLOGY of myocardial hypertrophy

Answer 16

• 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

Question 17

is hypertrophy a fast or slow process

Answer 17

slow

Question 18

increase in cell size results from what

Answer 18

increase protein production and # of myofilaments increase myocyte force and work capacity of the heart

Question 19

mechanisms of hypertrophy

Answer 19

1. mechanical stretch (increased work load)
2. agonists (eg. adrenergic hormones, angiotensin)
3. growth factors (eg. IGF-1)

Question 20

treatment with barbiturates leads to

Answer 20

hypertrophy of the SER in hepatocytes

Question 21

barbiturates increase the amount of what enzyme

Answer 21

cytochrome P450 in the liver to detoxify the drugs (catalyzes metabolism of drugs via oxidation)

Question 22

progressively what will happen in cytochrome P450 is increased in the liver

Answer 22

the pt will respond less to the drug bc of adaptation (catalyzes and metabolizes the drug via oxidation)

Question 23

normal genetic variations (polymorphisms) in P-450 lead to what

Answer 23

different levels of activity and sensitivity to drugs in pts

Question 24

what is hyperplasia

Answer 24

increase in the # of cells that make up the tissue/organ

Question 25

hyperplasia can be --- or ---

Answer 25

hormonal or compensatory

Question 26

hyperplasia often occurs with what

Answer 26

hypertrophy

Question 27

what is hormonal hyperplasia

Answer 27

hormones/growth factors stimulating cells leading to increase in the functional capacity of the tissue/organ

Question 28

what is mammary gland hyperplasia/hypertrophy (puberty/pregnancy)

Answer 28

increased proliferation of the glandular epithelium in the female breast leading also to increase in size of cells

Question 29

when does compensatory hyperplasia occur

Answer 29

when an organ that has regenerative capability increases the # of cells to compensate for loss of mass

Question 30

example of compensatory hyperplasia

Answer 30

liver regeneration in donors - following partial hepatectomy, remaining liver cells proliferate to regain original size and function

Question 31

what is pathologic hormonal hyperplasia

Answer 31

-results from excessive hormonal stimuli to target cells

Question 32

over stimulation and excess proliferation of cells can allow for

Answer 32

mutations to occur that can lead clonal formation and development of cancer

Question 33

patients with certain types of hyperplasias can have

Answer 33

an increased risk for developing cancer

Question 34

describe how the prostatic gland can undergo pathologic hormonal hyperplasia

Answer 34

under excess adrogenic stimulation, prostatic glands undergo hyperplasia leading to enlargement of the prostatic gland

Question 35

characteristics of atrophy

Answer 35

- reduced organelles - reduced metabolic need - decreased in cell size - decrease in # of cells - decreased in organ size - decrease in function of tissue

Question 36

main causes of atrophy

Answer 36

1. disease 2. denervation 3. decreased blood supply 4. malnutrition 5. hormonal under-stimulation

Question 37

what is atrophy

Answer 37

- an adaptation to changes in steady-state | - cell decreases in size and organelles, reducing its metabolic needs to adapt to the change

Question 38

atrophy: disure/inability to use

Answer 38

- 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

Question 39

atrophy: denervation

Answer 39

loss of nerve supply leads to loss of normal skeletal muscle function

Question 40

atrophy: decreased blood supply (schema/compression)

Answer 40

decrease in blood flow secondary to atherosclerosis will lead to senile atrophy

Question 41

atrophy: malnutrition

Answer 41

consumption of muscle as source of energy in malnourished pt leads to muscle wasting (cachexia)

Question 42

atrophy: hormonal under-stimulation

Answer 42

female reproductive organs become atrophied in absence of hormonal stimulation

Question 43

mechanism of atrophy

Answer 43

- decrease in cell # = apoptosis | - decreased in cell size (decreased protein synthesis, increased protein degradation)

Question 44

what are 2 protein degradation pathways that occurs with atrophy

Answer 44

1. ubiquitin degradation pathway - protein that needs to be degraded is tagged or ubiquinated 2. autophagy - cell will autodigest some of its own components

Question 45

what is metaplasia

Answer 45

change in phenotype (morphologic and functional type of a cell)

Question 46

why do phenotypic changes of a fully differentiated cell occur

Answer 46

to better endure the stressful envrionment

Question 47

is metaplasia reversible or reversible

Answer 47

reversible

Question 48

what is the most common type of metaplasia

Answer 48

columnar --> squamous | Can be seen in respiratory, salivary, pancreatic, cervical, glands, etc.

Question 49

if stress continues what happens to the metaplasia

Answer 49

metaplasia --> dysplasia --> cancer

Question 50

vitamin A deficiency can lead to

Answer 50

- squamous metaplasia | - deficiency due to general malnutrition or any condition with fat malabsorption

Question 51

what is vitamin A need for

Answer 51

- differentiation of specialized epithelium - ocular conjunctiva (lacrimal/mucus secreting epithelium) - upper respiratory passage (musociliary epithelium) - urinary tract (transitional epithelium)

Question 52

what is the mechanism of metaplasia

Answer 52

- 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