Pathoma Chapter 1 Flashcards
1
Q
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
what are common causes of injury?
A
inflammation nutritional deficiency or excess hypoxia trauma genetic mutations
25
slowly vs. acutely developing ischemia
slow: atrophy
acute: injury
26
_________ is the final electron acceptor
oxygen
27
how does decreased oxygen lead to a lack of ATP
impaired oxidative phosphorylation
28
causes of hypoxia
ischemia
hypoxia
decreased O2 carrying capacity
29
3 causes of ischemia
decreased arterial perfusion (atherosclerosis)
decreased venous drainage (Budd-Chiari syndrome)
shock- generalized hypotension resulting in poor tissue perfusion
30
aplasia
failure of cell production during embryogenesis
31
hypoxemia
PaO2 < 90%
low partial pressure of oxygen in the blood
32
hypoplasia
decrease in cell production during embryogenesis, resulting in small organ
33
causes of hypoxemia
high altitude
hypoventilation
diffusion defect
V/Q mismatch
34
how are PaO2 and SaO2 effected in anemia
only decrease in RBC mass not ability to bind O2 so:
| PaO2 and SaO2 normal
35
cherry-red appearance of the skin
CO poisoning
leads to coma and death
caused by tight binding of hemoglobin which reflects the light, but they are actually hypoxic
36
how are PaO2 and SaO2 effected in CO poisoning
PaO2 is normal but SaO2 is decreased b/c CO will bind limiting O2 binding
37
early sign of CO poisoning?
headache
38
cyanosis with chocolate colored blood
methemoglobinemia
39
What state of iron binds O2?
Fe2+
40
what is methemoglobinemia?
when iron in heme is oxidized to Fe3+ and cannot bind O2
41
labs in methemoglobinemia
normal PaO2, SaO2 decreased
42
treatment of methemoglobinemia
methylene blue to reduce the Fe3+
43
When do you see methemoglobinemia?
```
oxidant stresses (sulfa, nitrates)
newborns
```
44
why do newborns get methemoglobinemia
there is always oxidant stress and we have enzymes to reduce but newborn's are immature
45
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
46
hallmark of reversible injury
cellular swelling
47
cellular swelling
cytosol swells: loss of microvilli and membrane blebbing
swelling of RER, causing the dissociation of ER and ribosomes and decreased protein synthesis
48
hallmark of irreversible injury
membrane damage
| plasma membrane, mitochondrial membrane, and lysosome membrane
49
plasma membrane damage results in
cytosolic enzymes leaking into the serum and additional calcium entering the cell
50
mitochondiral membrane damage results in
loss of the electron transport chain (inner membrane) and cytochrome c leaking into cytosol and activating apoptosis
51
lysosome membrane damage results in
hydrolytic enzymes leaking into the cytosol and being activated by calcium
52
normal calcium concentration in the cell
very low- calcium is a messenger and turns on lots of pathways
53
hallmark of cell death
loss of nucleus
condensation (pyknosis)
fragmentation (karyorrhexis)
dissolution (karyolysis)
54
necrosis is always followed by
acute inflammation
55
necrotic tissue that remains firm with cell and organ structure preserved, but nucleus disappears
coagulative necrosis
56
appearance of area of infarcted tissue in coagulative necrosis
wedge-shaped and pale, wedge points to area of occlusion
57
when do you get coagulative necrosis?
ischemia of any organ except brain
58
what do you see in histology of coagulative necrosis?
recognizable structures but no blue nuclei
59
when do you get red infarction
if blood reenters a loosely organized tissue
60
explain the occurrence of red infarction in the testes
with testicular torsion, the vein is thin walled and gets block but the artery remains open and allows blood to enter
61
necrotic tissue with no structure or solidity- enzymatic lysis of cells and proteins
liquefactive necrosis
62
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
63
coagulative necrosis that resembles mummified tissue
gangrene necrosis "dry grangrene"
64
example of gangrene necrosis
lower limb ischemia or GI tract
65
how do you get wet gangrene?
superimposed infection on gangrenous necrosis leads to liquefactive necrosis
66
soft and friable necrotic tissue with cottage cehese-like appearance
caseous nerosis
| comb of coagulative and liquefactive necrosis
67
example of caseous necrosis
characteristic of granulomatous inflammation due to tuberculosis or fungal infection
68
necrotic adipose tissue with a chalky-white appearance due to deposition of calcium
fat necrosis with saponification
69
dystrophic calcification
necrotic tissue acts as a nidus for calcium deposition in the setting of normal serum calcium
ex: psamomma body
70
metastatic calcification
high serum calcium or phosphate levels lead to calcium deposition in normal tissue (like getting kidney stones from high serum calcium
71
fat necrosis caused by
trauma or pancreatitis-mediated damage of peripancreatic fat
72
saponification
fatty acids released by trauma or lipase join with calcium. Ex: dystrophic calcification
73
necrotic damage to blood vessel walls; leaking of proteins into vessel walls leads to bright pink staining of the wall microscopically
fibrinoid necrosis
74
fibrinoid necrosis is characteristic of ___
malignant hypertension (if young woman think preeclampsia and placental fibrinoid necrosis) or vasculitis
75
energy-dependent, genetically programmed cell death involving single cells or small groups of cells
apoptosis
76
what does a cell undergoing apoptosis look like?
dying cell shrinks and cytoplasm becomes eosinophilic
(pink from condensing)
nucleus condenses and fragments
77
apoptotic bodies
as the cell dies, apoptotic bodies fall from the cell and are removed by macrophages; apoptosis is not followed by inflammation
78
apoptosis is mediated by
caspases
79
caspases activate
proteases: break down cytoskeleton
endonucleases: break down DNA
80
what are the ways caspase are activated?
intrinsic mitochondrial
extrinsic receptor-ligand pathway
cytotoxic CD8+ T cell-mediated pathway
81
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
82
Bcl 2
inhibits cyt c from leaking from the inner mitochondrial membrane into the cytoplasm
83
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
84
CD95
Fas death receptor
85
cytotoxic T cell mediated pathway of caspase activation
preforins secreted by CD8+ T cells create pores in membrane of target cell
granzyme from CD8+ T cell enters pores and activates caspases
86
free radicals
chemical species with an unpaired electron in their outer orbit
87
physiologic generation of free radicals
oxidative phosphorylation
- cyt c oxidase
- partial reduction of O2 yields superoxide, hydrogen peroxide, and hydroxyl radicals
88
4 ways that free radicals are generated pathologically
ionizing radiation
(.OH)
inflammation- NAPDPH oxidase generates superoxide ions in O2 dependent killing by neutrophils
metals
(copper and iron)
drugs and chemicals (acetaminophen)
89
free radicals cause cellular injury by
peroxidation of lipids
| oxidation of DNA and protein
90
how do you eliminate free radicals?
antioxidants (glutathione, vit. A, C, E)
enzymes
metal carrier proteins (transferrin and ceruloplasmin)
91
enzymes that eliminate free radicals
```
superoxide dismutase
(mito): O2-. --> H2O2
glutathione peroxidase
(mito): GSH + free radical --> GSSH + H2O
catalase(peroxisome): H2O2 --> O2 + H2O
```
92
sequence of free radicals
O2 --> O2-. --> H2O2 --> OH. --> H2O
93
carbon tetrachloride
organic solvent used in dry cleaning that is converted to a free radical CCl3. in the liver and causes swelling of RER
ribosomes detach and protein synthesis is impaired leading to decreased apolipoproteins --> fatty change occurs
94
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
95
a misfolded protein that deposits in extracellular space --> damages tissues
amyloid
96
features of amyloid proteins
beta pleated sheet configuration
congo red staining and apple green birefringence with polarized light
often deposits around blood vessels
97
primary amyloidosis
systemic deposition of AL amyloid
| -derived from Ig light chains
98
primary amyloidosis is associated with
plasma cell dyscrasia (multiple myeloma): over production of the light chain --> leaks out and misfolds
99
secondary amyloidosis
AA amyloid deposition systemically of SAA (serum-associated amyloid protein)
100
SAA
acute phase reactant increased in chronic inflammatory states, malignancy and familial mediterranean fever
101
Familial Mediterranean fever
AR. dysfunction of neutrophils
presents with: fever, acute serosal inflammation (mimics appendicitis, arthritis, myocardial infarction), high SAA --> AA
102
clinical findings of systemic amyloidosis
```
nephrotic syndrome (most common)
restrictive cardiomyopathy or arrhythmia
tongue enlargement, malabsorption, hepatosplenomegaly
```
103
diagnosis of amyloidosis?
requires tissue biopsy, abdominal fat pad and rectum are accessible
104
treatment for amyloidosis?
damaged organ must be transplanted
105
localized amyloidosis
single organ
106
senile cardiac amyloidosis
non-mutated serum transthyretin deposits in the heart, usually asymptomatic
107
familial amyloid cardiomyopathy
mutated serum transthyretin deposits in the heart and causes a restrictive cardiomyopathy
108
non-insulin-dependent diabetes mellitus amyloidosis
amylin deposits in the islets of the pancreas (amylin is derived from insulin)
109
alzheimer's amyloidosis
A-beta amyloid deposits in the brain
| gene is on chromosome 21 (A beta amyloid is derived from beta-amyloid precursor protein)
110
clinical significance of A beta amyloid on chromosome 21?
alzheimer's occurs in patients with Down's syndrome at around age 40
111
dialysis associated amyloidosis
B2 microglobulin (component of MHC-I) deposits in joints
112
medullary carcinoma of the thyroid amyloidosis
calcitonin (produced by tumor cells) deposits in the tumor
113
FNA of thyroid shows "tumor cells in amyloid background"
medullary carcinoma of the thyroid
