Chapter 1: Growth Adaptations, Cellular Injury, and Cell Death Flashcards
1
Q
What are the steps involved in hypertrophy?
A
gene activation
protein synthesis
production of organelles
2
Q
hypertrophy vs. hyperplasia
A
hyerptrophy: larger cells
hyperplasia: more cells
3
Q
what cells can undergo hypertrophy only?
A
permanent tissues, like cardiac muscle, skeletal muscle, and nerve
4
Q
pathologic hyperplasia can progress to
A
dysplasia and cancer
5
Q
what tissue has no increased risk of cancer with hyperplasia?
A
prostate
BPH carries no increased risk for cancer
6
Q
atrophy
A
a decrease in organ size by both a decrease in size and number of cells
7
Q
how does a decrease in cell number occur?
A
apoptosis
8
Q
how does a decrease in cell size occur?
A
ubiquitination and proteosome degradation of cytoskeleton
autophagy of cellular components
9
Q
upiquitin-proteosome degradation
A
intermediate filaments of the cytoskeleton are tagged with ubiquitin and destroyed by proteosomes
10
Q
autophagy
A
autophagic vacuoles fuse with lysosomes containing hydrolytic enzymes to breakdown cellular components
11
Q
an increase in stress leads to _________
a decrease in stress leads to ___________
a change in stress leads to ___________
A
an increase in size
a decrease in size
a change in cell type
12
Q
metaplasia
A
change in cell type to better hand the new stress- change is adaptive
13
Q
most common cells to undergo metaplasia?
A
surface epithelium
14
Q
Barret’s esophagus is an example of
A
metaplasia
esophagus is normally lined by nonkeratinizing squamous epithelium and acid reflux causes it to change to nonciliated mucin-producing columnar cells
15
Q
metaplasia occurs via_______
A
reprogramming cells
16
Q
is metaplasia reversible?
A
in theory, yes, with the removal of the stressor
17
Q
what is one tissue that can become metaplastic with no increased risk of cancer?
A
apocrine metaplasia of the breast (fibrocystic change)
18
Q
vitamin A deficiency can cause metaplasia in ____
A
thin squamous lining of the conjunctiva- becomes stratified keratinizing squamous epithelium
=keratomalcia
19
Q
dysplasia
A
disordered cell growth
most often refers to proliferation of precancerous cells
20
Q
is dysplasia reversible?
A
in theory, it is reversible with alleviation of inciting stress
if it persists, dysplasia becomes carcinoma
21
Q
aplasia
A
failure of cell production during embryogenesis
22
Q
hypoplasia
A
decrease in cell production during embryogenesis, resulting in small organ
23
Q
what occurs when a stress exceeds the cells ability to adapt?
A
cellular injury
24
Q
slowly vs. acutely developing ischemia
A
slow: atrophy
acute: ischemia
25
_________ is the final electron acceptor
oxygen
26
how does decreased oxygen lead to a lack of ATP
impaired oxidative phosphorylation
27
3 causes of ischemia
1. decreased arterial perfusion (atherosclerosis)
2. decreased venous drainage (Budd-Chiari syndrome)
3. shock- generalized hypotension resulting in poor tissue perfusion
28
aplasia
failure of cell production during embryogenesis
29
hypoxemia
PaO2 < 90%
low partial pressure of oxygen in the blood
30
hypoplasia
decrease in cell production during embryogenesis, resulting in small organ
31
causes of hypoxemia
1. high altitude
2. hypoventilation
3. diffusion defect
4. V/Q mismatch
32
what occurs when a stress exceeds the cells ability to adapt?
cellular injury
33
cherry-red appearance of the skin and headache
CO poisoning
| leads to coma and death
34
cyanosis with chocolate colored blood
methemoglobinemia
35
labs in methemoglobinemia
normal PaO2, SaO2 decreased
36
treatment of methemoglobinemia
methylene blue
37
why do newborns get methemoglobinemia
there is always oxidant stress and we have enzymes to reduce but newborns are immature
38
broad effects of low ATP on cellular functioning
Na-K pump dysfunction: water and sodium buildup in the cell
Ca pump: calcium build up in the cell
aerobic glycolysis impaired- switch to anaerobic causing lactic acidosis, which denatures proteins and precipitates DNA
39
hallmark of reversible injury
cellular swelling
40
cellular swelling
cytosol swells: loss of microvilli and membrane blebbing
swelling of RER, causing the dissociation of ER and ribosomes and decreased protein synthesis
41
hallmark of irreversible injury
membrane damage
| plasma membrane, mitochondrial membrane, and lysosome membrane
42
plasma membrane damage results in
cytosolic enzymes leaking into the serum and additional calcium entering the cell
43
mitochondiral membrane damage results in
loss of the electron transport chain (inner membrane) and cytochrome c leaking into cytosol and activating apoptosis
44
lysosome membrane damage results in
hydrolytic enzymes leaking into the cytosol and being activated by calcium
45
normal calcium concentration in the cell
very low- calcium is a messenger and turns on lots of pathways
46
hallmark of cell death
loss of nucleus
condensation (pyknosis)
fragmentation (karyorrhexis)
dissolution (karyolysis)
47
necrosis is always followed by
acute inflammation
48
necrotic tissue that remains firm with cell and organ structure preserved, but nucleus disappears
coagulative necrosis
49
area of infarcted tissue in coagulative necrosis
wedge-shaped and pale
50
red infarction
if blood reenters a loosely organized tissue
51
necrotic tissue with no structure or solidity- enzymatic lysis of cells and proteins
liquefactive necrosis
52
characteristic of ischemia anywhere except the brain
coagulative necrosis
53
name 3 places where liquefactive necrosis characteristically occurs
brain infarction: proteolytic enzymes from microglial cells liquefy the brain
abscess: neutrophil proteolytic enzymes liquefy tissue
pancreatitis: proteolytic enzymes from pancreas liquefy parenchyma
54
coagulative necrosis that resembles mummified tissue
"dry grangrene"
| gangrene necrosis
55
example of gangrene necrosis
lower limb ischemia
56
soft and friable necrotic tissue with cottage cheese-like appearance
caseous nerosis
| comb of coagulative and liquefactive necrosis
57
example of caseous necrosis
characteristic of granulomatous inflammation due to tuberculosis or fungal infection
58
necrotic adipose tissue with a chalky-white appearance due to deposition of calcium
fat necrosis with saponification
59
dystrophic calcification
necrotic tissue acts as a nidus for calcium deposition in the setting of normal serum calcium
60
metastatic calcification
high serum calcium or phosphate levels lead to calcium deposition in normal tissue (like getting kidney stones from high serum calcium
61
fat necrosis caused by
trauma or pancreatitis-mediated damage of peripancreatic fat
62
necrotic damage to blood vessel walls; leaking of proteins into vessel walls leads to bright pink staining of the wall microscopically
fibrinoid necrosis
63
energy-dependent, genetically programmed cell death involving single cells or small groups of cells
apoptosis
64
what does a cell undergoing apoptosis look like?
dying cell shrinks and cytoplasm becomes eosinophilic
| nucleus condenses and fragments
65
apoptotic bodies
as the cell dies, apoptotic bodies fall from the cell and are removed by macrophages; apoptosis is not followed by inflammation
66
apoptosis is mediated by
caspases
67
caspases activate
proteases: break down cytoskeleton
endonucleases: break down DNA
68
what are the ways caspase are activated?
intrinsic mitochondrial
extrinsic receptor-ligand pathway
cytotoxic CD8+ T cell-mediated pathway
69
intrinsic mitochondrial pathway of caspase activation
cellular injury, DNA damage or loss of hormonal stimulation leads to inactivation of Bcl2
cytochrome c leaks from the inner mitochondrial membrane into the cytoplasm and activates caspases
70
Bcl 2
inhibits cyt c from leaking from the inner mitochondrial membrane into the cytoplasm
71
extrinsic receptor-ligand pathway of caspase activation
Fas ligand binds FAS death receptor (CD95) to activate caspase
tumor necrosis factor (TNF) binds TNF receptor on the target cell to activate caspases
72
CD95
Fas death receptor
73
cytotoxic T cell mediated pathway of caspase activation
perforins secreted by CD8+ T cells create pores in membrane of target cell
granzyme from CD8+ T cell enters pores and activates caspases
74
free radicals
chemical species with an unpaired electron in their outer orbit
75
physiologic generation of free radicals
oxidative phosphorylation
- cyt c oxidase
- partial reduction of O2 yields superoxie, hydrogen peroxide, and hydroxyl radicals
76
4 ways that free radicals are generated pathologically
1. ionizing radiation
2. inflammation- NAPDPH oxidase generates superoxide ions in O2 dependent killing by neutrophils
3. metals
4. drugs and chemicals
77
free radicals cause cellular injury by
peroxidation of lipids
| oxidation of DNA and protein
78
enzymes that eliminate free radicals
superoxide dismutase
glutathione peroxidase
catalase
79
carbon tetrachloride
organic solvent used in dry cleaning that is converted to a free radical in the liver and causes swelling of RER
ribosomes detach and protein synthesis is impaired and fatty change occurs
80
reperfusion injury
return of blood to ischemic area results in O2-derived free radicals, which continue to damage tissue
this is the reason that there is a continued rise in cardiac enzymes after reperfusion of infarcted tissue
81
a misfolded protein that deposits in extracellular space and damages tissues
amyloid
82
features of amyloidosis in all proteins
beta pleated sheet configuration
| congo red staining and apple green birefringence with polarized light
83
primary amyloidosis
systemic deposition of AL amyloid
| -derived from Ig light chains
84
primary amyloidosis is associated with
plasma cell dyscrasia (multiple myeloma)
85
secondary amyloidosis
AA amyloid deposition systemically of SAA (serum-associated amyloid protein)
86
SAA
acute phase reactant increased in chronic inflammatory states, malignancy and familial mediterranean fever
87
Familial Mediterranean fever
dysfunction of neutrophils
| presents with: fever, acute serosal inflammation (mimics appendicitis, arthritis, myocardial infarction)
88
clinical findings of sysmteic amyloidosis
```
nephrotic syndrome (most common)
restrictive cardiomyopathy or arrhythmia
tongue enlargement, malabsorption, hepatosplenomegaly
```
89
treatment for amyloidosis?
damaged organ must be transplanted
90
localized amyloidosis
single organ
91
senile cardiac amyloidosis
non-mutated serum transthyretindeposits in the heart, usually asymptomatic
92
familial amyloid cardiomyopathy
mutated serum transthyretin deposits in the heart and causes a restrictive cardiomyopathy
93
non-insulin-dependent diabetes mellitus amyloidosis
amylin deposits in the islets of the pancreas (amylin is derived from insulin)
94
alzheimer's amyloidosis
A-beta amyloid deposits in the brain
| gene is on chromosome 21
95
dialysis associated amyloidosis
B2 microglobulin (component of MHC-I) deposits in joints
96
medullary carcinoma of the thyroid amyloidosis
calcitonin (produced by tumor cells) deposits in the tumor
97
FNA of thyroid shows tumor cells in amyloid background
medullary carcinoma of the thyroid
98
Epithelium-- 3 broad categories
Squamous Cell Epithelium
--> keratinizing/non-keratinizing
Columnar Epithelium
--> ciliated?
Transitional
--> really only the bladder lined with this
99
normal esophageal lining?
nonkeratinizing squamous epithelium
100
What can happen after trauma to muscle?
Myositis ossificans
| metaplasia of muscle to bone during healing after trauma
101
fibromuscular dysplasia
Most commonly affects renal artery and carotid artery
102
What symptoms does Vitamin A deficiency present with?
Vitamin A necessary for differentiation of specialized epithelial surfaces such as the conjunctiva covering the eye, thus deficiency can lead to
keratomalacia or stratified keratinizing squamous epithelium
103
Most common cause of Budd-Chiari syndrome
Polycythemia Vera
104
Describe the path of oxygen to tissue using lab values
FiO2 --> PAO2 --> PaO2 --> SaO2
pressure of oxygen in air --> pressure of oxygen in alveoli --> pressure of oxygen in blood --> saturation of hemoglobin
105
Lab values in hypoventilation
Increased CO2 causes decreased O2 which means O2 sats go down
106
Chocolate colored blood with cyanosis. lab values? treatment?
Methemoglobinemia
PaO2 normal
SaO2 decreased
Iron oxidized to Fe+3 and cannot bind oxygen. Seen with OXIDANT STRESS such as nitryl or sulfa drugs.
TREATMENT: Methylene blue, which catalyzes natural reduction of methemoglobin reductase by offering an electron acceptor
107
Describe pathophys of low ATP
1. ) disruption of ATP pump leads to Na+ influx into cell
2. ) Ca+2 pump needs ATP so influx of Ca+2 as well
3. ) Ca+2 activates enzymes
4. ) Anaerobic glycolysis causes lactic acid buildup which lowers pH and precipitates DNA
108
Hallmark of reversible injury and what it leads to
Cellular Swelling
1. ) loss of microvilli
2. ) cellular blebbing
3. ) ribosomes fall off rough ER causing decreased protein synthesis
109
Hallmark of irreversible damage is?
what it leads to...
Membrane damage
1. ) allows enzymes to leak into the serum(cardiac troponin after MI/necrosis)
2. ) more calcium enters cell
3. ) mitochondrial membrane damage breaks electron transport
4. ) that same mitochondrial membrane damage allows cytochrome c to leak out which activates apoptosis
5. ) lysosomal membrane damage allows hydrolytic enzymes to leak into cell and wreak havoc
110
What are the macrophages of the CNS
microglial cells
111
Acute inflammation can be caused by...
infection OR necrosis
neutrophil count will increase in both
112
Which organs have white infarcts?
Heart, Kidney, Spleen
113
Which organs have red infarcts?
lungs, liver, testes, ovaries, gut
114
what is fibrinoid necrosis
necrotic damage to blood vessel wall causes leaking of proteins into vessel wall(including fibrin)
115
necrosis associated with hypertension or vasculitis
fibrinoid necrosis
common example is fibrinoid necrosis of placenta secondary to high Bp due to pre-eclampsia
116
Malignant hypertension can cause what?
fibrinoid necrosis of blood vessels
117
Apoptosis activation -- intrinsic mitochondrial pathway
cellular or DNA damage or loss of hormonal stimulation can cause inactivation of Bcl2
Inactivation of Bcl2 --> leakage of cytochrome c from inner mitochondrial membrane into cytoplasm --> cytochrome c activates caspases in cytoplasm --> caspases activate proteases that wreak havoc, in an orderly fashion
118
Apoptosis activation -- extrinsic receptor-ligand pathway
FAS ligand binds FAS death receptor(CD95) on target cell, activating caspases
example: negative T-cell selection in Thymus
OR
TNF binds TNF receptor on target cell activating caspases
119
Chronic Granulomatous Disease
deficiency in NADPH oxidase. However if extrinsic hydrogen peroxide provided, MPO can make bleach and be bacterial. Thus catalase positive organisms are particularly dangerous to these people.
120
NBT dye is for what?
oxidative burst! or...
O2 --> O2 free radical
catalyzed by NADPH oxidase
121
MPO deficiency
These people will respond to NBT dye test. But they cannot make HOCl(bleach) because of defective MPO and thus are susceptible to chronic infection
