Powerpoint-Chap1 Flashcards
1
Q
What are the main contributors to cellular aging
A
telomere shortening, environmental insults, DNA repair defects, Abnormal growth facto signaling
2
Q
How is it hyposthesized that sirtuins reduce aging
A
insulin sensitization, decreasing free radicals and prevention of apoptosis
3
Q
What to sirtuins require for action
A
NAD
4
Q
What pharm agent induces Sirt1 activity
A
resveratrol
5
Q
What is the first line of defense against cell injury
A
atrophy, hypertrophy, hyperplasia, metaplasia for ways of adaptation
6
Q
inability of a cell to adapt leads to what
A
irreversible or reversible injury
7
Q
Addition of growth factors and hormones can lead to what cell adaptations
A
hyperplasia and hypertrophy
8
Q
decreased nutrients and stimulation can lead to what cell adaptations
A
atrophy
9
Q
chronic irritation whether physical or chemical can lead to what cellular adaptation
A
metaplasia
10
Q
actue transient hypoxic or injurious attacks lead to what type of cell injury
A
reversible. cell may swell or there are fatty changes
11
Q
progressive and severe hypoxic or chemical attacks lead to what type of cell injury
A
irreversible
cell death by necrosis or apoptosis
12
Q
metabolic alterations can lead to what type of cell response
A
intracellular accumulation, calcification
13
Q
cumulative sublethal injury results in what type of cell response
A
cellular aging
14
Q
having a cast causes what type of atrophy
A
decreased workload/disuse
15
Q
what can cause denervation
A
disease or lack of use
16
Q
what is worse, hypoxia or ischemia
A
ischemia
17
Q
what is marasmus
A
really total malnutrition
breakdown fat really well still
18
Q
what is cachexia
A
wasting away from diseases that cannot be reversed nutritionally
19
Q
how does atrophy happen from endocrine system
A
loss of stimulation from those hormones
20
Q
what is a pressure atrophy
A
presses on surrounding structures causing atrophy in surrounding areas
21
Q
what is a common cause of pressure atrophy
A
decubitus ulcers
22
Q
what are types of atrophy from inflammatory and immunologic processes
A
atrophic gastritis, celiac sprue
autoimmune!
23
Q
what is atrophy senility
A
senile osteoporosis
aging!
24
Q
What are the main mechs of atrophy
A
ubiquitin-proteasome protein breakdown pathway
accelerated proteolysis in catabolic conditions
25
What is lipofuscin
left over cell components after breakdown--> aging pigment
| golden brown
26
what is brown atrophy
atrophy with lots of lipofuscin
27
What are the autophagy bodies called
residual bodies
28
what is kwashiorkor. signs?
moon face, swollen abdomen, thin muscles.
deficiency only in proteins.
(watered down formula)
massive edema
29
what occurs in cell metabolism in the casted limbs
lose proteoglycans in articular cartilage
decrease strength ligaments(atrophy)
osteopenia(loss of bone mass)
30
what causes fat atrophy
starvation or dissuse. replaced m with fat
31
when can function return after motor denervation of skel m
3-5 weeks
| useless after 20-24 months
32
what are the cellular changes in hypertrophy
increased cytoplasm, increased ribosomes, more protein, nucleolus enlarged ( increased RNA, DNA)
33
what are the cellular changes in hyperplasia
nucleus enlarged but less basophilic(chromatin is dispersed)
| increased DNA transcription
34
What are some causes of hypertrophy and hyperplasia
```
increased functional demands
patholdy
compensation
excessive nutrition
increased blood flow
endocrine stimulation
mechanical factors
```
35
bladder hypertrophy is an example of what cause of hypertrophy
mechanical
36
prostatic hyperplasia is an example of what cause of hyperplasia
endocrine stimulation
37
Hypertrophy without hyperplasia occurs where****
heart and skel m
38
what organs of body commonly have increased functional demands
kidney, striated m, smooth m
39
how does the kidney respond to increase demand
hypertrophy and hyperplasia
40
how does striated m respond to increased demand
endurance- increased number and volume mitochondria
| resistant- hypertrophy of contractile elements and increased capillary network
41
how does smooth m respond to increased demand
hypertrophy and hyperplasia
| VASCULAR smooth muscle polyploidy
42
what is polyploidy
increase number DNA content
43
What are the two main pathways for mycardial hypertrophy
phosphinositide3-kinase/AKT pathway
| GPCRs
44
what is the main pathway of myocardial hypertrophy from exercise
Phosphinositide 3-Kinase/AKT pathways
45
what is the main pathway for pathologic myocardial hypertrophy
GPCR downstream cascade signaling increase
46
What are the main changes in myocardial hypertrophy
switch of contractile protein to fetal forms
| early development genes re-expressed
47
what is the fetal form of myocardium contractile protein
alpha heavy to beta heavy chain (energy economical)
48
what are the early development cardiac genes
increased ANF
49
what does increased ANF cause
increased Na excretion in kidney
| decrease intravascular volume and pressure (vasodilates)
50
What can cause myocardial hypertrophy
mechanical stress worload
agonists like alpha adrenergic and Angiotensin
Growth factors like IGF-1
51
What are permanent changes from reversible cardiac hypertrophy
increased nuclear size and the scarring remains from initial insult- decreased compliance
52
what causes subcellular hypertrophy
cytochrome P450 activation can break down toxins(drugs and ethanol)
53
what happens with increased use of drugs and toxins
hypertrophy of the ER so can detoxify more of the toxins. Products from breakdown process may be more injurious because release ROS
54
What are physiologic causes hyperplasia
hormonal and compensatory
55
what are pathologic causes hyperplasia
hormonal (gigantism)
increased functional demand
persisten cell injury
infectious agents
56
what type of injury is from lichen simplex chronicus
pathologic hyperplasia due to persisten cell injury
57
what are the main mech of hyperplasia
GF driven proliferation of mature cells
| Increased output of new cells from stem cells
58
What happens after you remove a lobe of liver
the rest of the liver hypertrophies and hyperplasia. "compensatory"
59
What are the stem cells in liver
oval cells or "satellite"
60
if the hepatocytes in a liver cannot replicate what happens
the oval cells take over and regenerate new lineage of cells
61
In the menstrual cycle what occurs to cells in proliferative, secretory and menstrual phases
proliferative is hyperplasia
secretory is hypertrophy
menstrual is atrophy
62
what metaplasia occurs from smoking
squamous metaplasia of ciliated columnar epithelium
63
chronic irritation to the endocervix leads to what metaplasia
squamous metaplasia of endocervical glandular epithelium
64
chronix reflux esophagitis leads to what metaplasia
intestinal and gastric glandular metaplasia
65
what layer of epithelium undergoes the metaplasia
begins at the base where the less differentiated cells are
66
What vitamin is critical for regulating gene transcription
Vit A thru retinoid R
67
Where is the main problem caused by Vit A deficiency
eye and the production of keratinizing metaplasia of the specialized epithelium
68
What is the most common example of metaplasia
switch from columnar to squamous as a protective measure
69
What is the double edged sword of squamous metaplasia
dec cilia in bronchi inc in mucus
| malignant transformation may occur
70
What causes periductal mastitis
keratin trapped after metaplasia
ruptures the duct resulting in inflammatory response
fistulas occur recurrently thereafter
71
what is a common example of glandular metaplasia
barretts esophagus
72
What is Barretts esophagus
at gastroesophageal junction there is gastric acid that refluxes and transitions the squamous cells into columnar with lots of goblet cells
73
What are the structures of the cell that change in cell injury
```
nuclei
ER
mitochondria
PM
other cell structures
```
74
What is oncosis
cell death with swelling (associated with necrosis)
75
What pathway occurs from ischemia that goes directly to irreversible injury
membrane damage
76
decrease ATP production ultimately leads to what if it is persistent
necrosis
77
If you turn off Na K pump what happens
increase intracellular Na, water follows
| swelling
78
What is the sequence Ca after membrane dysfunction.
increase intracell Ca- activation phospholipases, digest cell
79
What does the mitochondrail release
cytochrome C which ultimately signals apoptosis
80
What do mitochondria look like when injured
megamitochondria
81
what commonly causes megamitochondria
alcoholic liver disease
82
If oxygen acceps one electron what is it
superoxide O2negative
83
If oxygen accepts two electrons what is it
hydrogen peroxide H2O2
84
if hydrogen peroxide is presence of divalent Fe2+
hydroxyl radical OHelectron
85
What is the fenton rxn
Fe2+ +H2O2 --> Fe3+ +OH- +OHelectron
86
What radical causes most damage
hydroxyl radical
87
what are natural mech to remove free radicals
```
antioxidants
storage and transport proteins
superoxide dismutatses
Glutathione peroxidases
catalase
```
88
What are our antioxidants
Vit E and A, ascorbic acid and glutathione (cytosol)
89
what are our storage proteins for free radicals
transferrin, ferritin, lactoferrin, ceruloplasmin
90
what are the superoxide dismutases that we have
manganese SOD (mitochondria
copper-zinc SOD (cytosol)
these all convert O2- to H2O2
91
what is the glutathione peroxidase
mitochondria converts Ohelectron to H2O2 and O2
92
what is clinically important of the ratio of oxidized glutathione GSSG to reduced form GSH
reflects cells ability to oxidize free radicals
93
What does the catalase do
peroxisomes
| decompose H2O2 to H2O and O2
94
What do free radicals do in cytosol (ROS)
disrupt PM lipids
misfolded proteins
DNA damage
95
What is the hydroxyl radical from
H2O by hydrolysis
| H2O2 by fenton reaction
96
what is the mechanism of innactivation of hydroxyl radical
conversion to H2O by glutathione peroxidase
97
What happens if CCl4 gets in ER
P450 oxidases act and form CCl3- which inhibits protein synthesis and inhibits apoprotein synthesis and damages PM
98
what can occur if apoprotein synthesis is inhibited
steatosis
99
What is hydropic degeneration
swollen cells with bubbles inside (vacuoles) from hypoxic injury
100
Why does repercussion cause injury
letting O2 back in so increase amount of ROS, also adding iron into area. everything is leaky = inflammation
101
what is the prime time to do recatheterization
within 20 minutes is prime time
102
Describe differences in PM between necrosis and apoptosis
necrosis has disrupted PM
| apoptosis the PM still intact, maybe in apoptotic bodies
103
Is necrosis both physiologic and pathologic
strictly pathologic
104
what is karyolysis
no more DNA, it was all chewed up
| before it would be karyorrhexis
105
What are morphologic features of necrosis
eosinophilia because loss ribosomes(basophilic)
eosin dye is taken up by denatured proteins
swelling of mitochondria with Ca bodies
pyknosis, karyorrhexis and karyolysis
106
what does early cell injury from reperfusion look like
microvilli loss and blebbing
107
what do cells look like after irreversible ischemic injury
swollen mitochondria with densities
disrupted cell membranes
ruptured lysosomes
dense pyknotic/fragmented nucleus
108
best sign for irreversible morphologic feature
PM is ruptured
109
What is coagulative necrosis
denaturation of protein is the primary pattern
| myocardial infarct
110
what is caseous necrosis
distinct amorphous necrosis
| mycobacterium TB
111
what is liquefactive necrosis
enzyme digestion is dominant
| bacterial abscess, cerebral infarct
112
what is gangrene
necrosis with or without putrefaction
113
Where does fat necrosis happen
in acute pancreatitis saponification
114
when does fibrinoid necrosis take place
hypertension
immune complex deposition
vasculitis
115
where is coagulative necrosis seen
hypoxic death of cells in tissues, NOT brain
116
what is the morphology of coagulative necrosis
homogenous glassy eosinophilic appearance due to loss of cytoplasmic RNA(basophilic) and glycogen
Pinker than normal
117
what is an hemorrhagic infarct
dual blood supply with large amounts of loose CT into which hemorrhage may occur
118
what is a pale or anemic infarct
sudden arrest of circulatory blood flow. usually from thrombus or embolus
119
What type of degradation is dominant in liquefactive necrosis
enzyme digestion- completely
120
What is Pus
the left over from neutrophils and WBCs in the area
121
What can lead to abscess propagation
bacteremia
| local expansion
122
what plane does pus travel along
fascial planes
123
why is affected tissue from gangrene black
deposition of iron sulfide from degraded Hb
124
what is dry gangrene
black brown, mummified appearance (coagulative necrosis)
125
what is wet gangrene
bacterial superinfection of necrotic material with liquefactive necrosis
126
what is gas gangrene
wet gangrene with infarction of bowel since rapid bacterial superinfection happens
127
diabetics have what type gangrene usually
wet
128
what usually causes gas gangrene
clostridium welche and Cl perfringes
129
what conditions can gas gangrene live in
anaerobic conditions
130
under microscope what does caseous necrosis look like
granular debris, fragmented coagulated cells
| inflammatory granulamtous reaction
131
fibrinoid is what color histo
light pink
132
what can cause fibroid necrosis
aging, HTN or immune complex deposition in arteriolar walls
133
what causes pancreatic fat necrosis
large amounts of hydrolytic enzymes
| phospholipase and proteases attacking adipocyte PM
134
How does saponification occur in pancreatic fat necrosis
pancreatic lipase hydrolyzes triglycerides
| producing FFA which combine with Ca to form soaps
135
When does traumatic fat necrosis occur.
| if occurs in breast tissue can be mistaken for?
after crushing injury
| breast cancer
136
What are causes of pancreatitis
steroids, alcohol, trauma
137
what are complications of pancreatitis
pancreatic pseudocyst
fat necrosis
can be fatal
138
what does pancreatitis look like under microscope
adipocytes show loss of nuclei and blueish color
| basophilic calcium deposits
139
What can we measure necrosis by in the liver?
GGT AST ALT from liver
| alkaline phosphatase from biliary obstruction
140
how do we measure necrosis of CV system
creatine kinases, LDH and troponins from myocardial cells
141
how do we measure necrois in pancreas
lipase and amylase levels
142
how do we measure necrosis from RBC
LDH and Hb
143
What are cell injuries that lead to apoptosis
DNA damage, abnormal protein accumulations
144
what mechanisms in body trigger apoptosis
mitochondrial cytochrome C
| p53 if DNA damage is unrepairable
145
What is the intrinsic pathway of apoptosis
mitochondrial
| action of sensors and effectors of the Bcl-2 family inducing leakage of the mitochondrial proteins
146
What is the extrinsic pathway of apoptosis
death receptor mediated caspase activation
147
What are the pro-apoptotic proteins that form channels in the mitochondria
Bax and Bak
148
what proteins leak from mitochondrial layers
cytochrome c and other proteins that lead to caspase activation
149
What ligands and proteins are included in the death receoptor pathway of apoptosis
FasLigand binds tot he Fas-associated death domain which downstream activates caspase 8
150
What inflammatory mediator is capable of inducing apoptosis
cytokine TNF
151
what does TNF do to tumor blood vessels
induces thrombosis
152
Describe the CTL mediated apoptosis
CTL secrete perforin so that granzymes can enter and activate caspases to initiate effector phase
153
what protein prevents cell replication when DNA damage is detected
p53
154
what main type of disease is characterized by defective apoptosis
cancer
155
what type of diseases/injuries involve increased apoptosis
neurodegenerative diseases- misfolded proteins build up
ischemic injury
death of virus infected cells
156
What causes dysregulated apoptosis
unable to cope with a large number of misfolded proteins
157
What is the main mechanism of DNA breakdown in apoptosis
Gene activation and endonucleases
158
how does apoptosis and necrosis appear on a gel electrophoresis
apoptosis in laders
| necrosis in large smear
159
What is the role of alpha1-antitrypsin
inhibits neutrophil elastase
160
what occurs in an alpha1-antityrpsin deficiency
accumulation of abnormally folded protein in ER
causes hepatocyte death(apoptosis)
lung disease(enzymatic digestion)
161
What is Reye syndrome
children with viral infection and concomitant use of aspirin results in mitochondrial injury leading to decreaed FFA oxidation
162
What occurs to organs in Reye syndrome
liver develops steatosis with micro vesicular pattern
163
What are signs of Reye syndrome
vomiting, liver failure and neurologic symptoms
164
What can cause accumulation of triglycerides
diabetes, starvation, ethanol, hypoxia and Reye syndrome, toxins, malnutrition CCL4
165
how does diabetes and starvation lead to accumulation triglycerides
increased supply of FFA
166
how does ethanol lead to accumulation triglycerides
increased supply of FFA
increased esterification of FFA to triglyceride
decreased oxidation of FFA
167
how does hypoxia and reye syndrome lead to accumulation of triglycerides
decreased oxidation of FFA
168
how do toxins lead to accumulation of triglycerides
decreased oxidation of FFA
| reduced apoprotein availability
169
how does malnutrition and CCl4 lead to accumulation of triglycerides
reduced apoprotein availability
170
thin filaments are targets for what
toxins like mushrooms
171
what filament is responsible for rigor mortis
thin
172
what filaments are responsible for mallory alcoholic hyaline
intermediate
173
What protein in our bodies inactivates toxins
cytochrome p450
174
what induce cytochrome p450
ethanol, phenobarbital and tobacco
175
what surgery protects against second drug effect of cytochrome p450
partial hepatectomy
176
What occurs with cell injury due to alcohol
```
cytochrome p450 induction
hydropic changes
fatty changes
hyaline degeneration leaving mallory bodies
also causes pancreatitis
```
177
how do mallory bodies stain with H&E
eosinophilic
178
what is the genetic syndrome with defective dynein arms
kartagener syndrome
179
what happens with kartagener syndrome
```
primary ciliary dyskinesia
leading to brochiectasis
chronic sinusitis
infertile males
subfertile females
```
180
What other strange anomaly occurs with kartagener syndrome
situs inversus
181
What is steatosis
accumulations of FA and triglycerides
182
What occurs with intracellular accumulations of cholesterol
atherosclerosis, xanthomas, cholesterolosis and Niemann-Pick type C
183
what occurs wih intracellular accumulations of proteins
proteinuria, plasma cell dyscrasias, cytoskeletal proteins, abnormal proteins
184
what occurs with intracellular accumulations of glycogen
DM and glycogenoses
185
What is mallory hyaline
keratin intermendiate filaments building up
186
what are neurofibrillary tangles
accumulations of neurofilaments
187
What occurs in diabetic hepatopathy
glycogenosis (accumulation glycogen)
188
Lipofuscin granules accumulate in what tissue
cardiac myocyte
189
What is hemosiderin
breakdown of Hb, ferritin micelles
190
what stain is used to visualize iron in Hb
prussian blue stain
191
accumulation of melanin presents how on epidermis
blue nevus
192
What stain is used to visualize copper
rhodamine
193
what is anthracosis
accumulation of coal
194
what is it called when there is accumulation of lead and where is this seen in people
plumbism
gingival lead line
hemolytic anemia and renal tubular necrosis from toxic effects of lead
195
what is dystrophic calcification
in site of previous tissue damage
| may end up with bony metaplasia
196
Where does metastatic calcifaication show up
in alkaline environment
| interstitium of acid secreting organs (stomach, kidney, lung)
197
What other pathologies usually exist with metastatic calcification
HyperPTH
vit D excess
bone destruction
idiopathic hypercalcemia of infant, aluminum intoxication, milk alkali syndrome
