Patho infl. and recovery Flashcards
1
Q
What 3 factors induce ROS production and lead to mitochondria damage?
A
Radiation, toxins, reperfusion
2
Q
Where originates oxygen used to form ROS in reperfusion?
A
Restoration of arterial blood flow to an affected limb floods ischemic tissue with oxygen. This molecular oxygen reacts with enzymes (…) to form ROS.
3
Q
Molecular oxygen reacts with …………. (3) to form ROS.
A
xantine oxidase, NADPH oxidaze, NO synthase
4
Q
What 3 types of ROS are formed after molecular oxygen reacts with some enzymes?
A
superoxide, hydroxyl radicals, singlet oxygen
5
Q
How ROS disrupt cellular functions? (3)
A
DNA mutations, protein synthesis disruption/protein damage, membrane lipis peroxidation
6
Q
What are antioxidant enzymes that convert ROS to oxygen and water?
A
superoxide dismutase, glutathione peroxidase, calatase
7
Q
What reaction is catalyzed by catalase/glutathione peroxidase?
A
hydrogen peroxide (H2O2) –> H2O (it is called detoxification)
8
Q
When are neutralized ROS generated during cellular respiration?
A
Before it causes damage
9
Q
What are the result molecules in detoxification?
A
Oxygen and water
10
Q
Why there is ROS damage to cell after reperfusion if normally cells are capable to neutralize it?
A
Because in postischemic damage, the production of ROS exceeds the neutralizing capabilities of antioxidant enzymes (high oxidative stress) –> cell injury and death
11
Q
What is high oxidative stress?
A
ROS exceeds the neutralizing capabilites of antioxidant enzymes
12
Q
Eg there is prostata cancer with radiation treatment. What condition may develop?
A
acute radiation enteritis
13
Q
What are 2 mechanisms that cause cell damage when used ionizing radiation?
A
DNA double-stranded breakage and generation of ROS
14
Q
DNA double-strand breakage in ionizing radiation?
A
Breakage of both strands is required. Single-strand breaks can be repaired by polymerase
15
Q
What is used to form ROS (tipo unstable molecules) by ionization?
A
WATER. Unstable molecules formed by the ionization of water.
16
Q
Radiation-induced DNA damage impairs ………. and initiates ………….. of susceptible cells.
A
Mitosis; apoptosis
17
Q
What are susceptible cells for radiation?
A
Intestinal crypt stem cells and other highly proliferative cells (eg, cancer cells, hematogenous precursors)
18
Q
What immune response is innitiated by cellular damage due to radiation?
A
induced immune response –> increased proinflammatory cytokines + migration of leukocytes (eg neutrophils) –> Inflammation –> production of additional ROS that leads to contribution of radiation-induced tissue damage
19
Q
What proinflammatory cytokines participate in radiation-induced cell damage?
A
IL-1, IL-6, TNF-alpha
20
Q
What is the result of GI mucosal denudation due to radiation therapy?
A
decreased absorptive area –> diarrhea
21
Q
What causes diarrhea in radiation therapy?
A
GI mucosal denudation –> decreased absorptive area –> diarrhea
22
Q
What are late GI complications due to radiation therapy?
A
Intestinal fibrosis = strictures, adhesions, bowel obstruction
23
Q
As an antioxidant, ………………….. neutralizes ROS, preventing …………..
A
superoxide dismutase; preventing cell injury.
24
Q
Cytochrome P450 enzymes metabolize ……………. and ………..
A
endogenous toxins as well as drugs.
25
How can cytochrome P450 enzymes can lead to hepatotoxicity?
Cytochrome P450 enzymes metabolize endogenous toxins as well as drugs. They are capable of producing ROS, which can contribute to the hepatotoxicity seen with certain drugs.
26
What enzyme is bactericidal, but also causes oxidative damage to host cells?
myeloperoxidase
27
NADPH oxidase catalyzes the reduction of ............... to .............., aiding in bacterial destruction by phagocytic cells.
molecular oxygen to superoxide free radicals
28
What reaction catalyzes NADPH oxidase?
reduction; molecular oxygen to superoxide free radicals
29
What is the effect on bacterias y superoxide free radicals that are produces by NADPH oxidase?
It aids bacterial destruction by phagocytic cells
30
Proteasome activity normally increases in ................................
response to oxidative stress
31
the ubiquitin-proteosome system is inhibited by .................
ionizing radiation
32
radiation-induced tissue damage occurs primarily through the .................
Generation of free radicals
33
Ionizing radiation causes ............... and ...............damage
cellular and DNA
34
What triggers progressive inflammation and tissue damage in radiation therapy?
Ionizing radiation causes cellular and DNA damage primarily through generation of reactive oxygen species, which can trigger progressive inflammation and tissue damage.
35
What breakdowns proteins?
Ubiquitin protease pathway
36
Viral infection. Need to activated cellular immune. What is needed for activation and what system participates?
Need viral protein presentation to effector immune cells (eg CD8 lymph). These proteins are broken down by ubiquitin protease pathway and hydrolyzed peptides are presented to effector cells.
37
What proteins are broken down by ubiquitin-proteasome pathway?
native and foreign intracellular (eg viral) proteins
38
What initiates UPP?
Ubiquitin ligase
39
What does ubiquitin ligase?
It recognizes proteins and catalyzes the attachement of ubiquitin
40
What specific feature have proteins that participate in UPP and eventually are broken down?
Those proteins are tagged with ubiquitin. Then they are broken down by proteosome to peptide fragments --> recycled to amino acids
41
What catalyzes breakdown of proteins in UPP?
proteasome; proteins to peptide fragments
42
What is presented to MHC class I in viral infection?
PEPTIDE FRAGMENTS!!!!!
| The are got after proteins are broken down by proteasome
43
What cell process if initiated by cytotoxic CD8 when eg viral peptides are presented?
apoptosis
44
What process happens when apoptosis is initiated by cytotoxic CD8?
activation of caspase cascade through the release perforin and granzyme
45
What is activated by perforins and granzymes?
caspase cascade
46
What state is cachexia?
hypermetabolic
47
What drives cachexia?
elevated proinfalmmatory cytokines (eg TNF-alpha, IL-6)
48
What is stimulated by TNF-alpha and IL-6 in cachexia?
UPP, therefore there is the degradation of muscle proteins (actin, myosin)
49
In cancer-related cachexia, high levels of pro-inflammatory cytokines lead to increased ............................. of .................... proteins, which in turn leads to extensive skeletal muscle loss
ubiquitination of sarcomeric muscle proteins -_> extensive skeletal muscle loss
50
How is called the destruction of targeted proteins?
selective proteolysis
51
Oligopeptides formed within within proteasomes further degraded by ............................... into ...........
cytosolic peptidase into individual amino acids
52
Necrosis is characterized by ........................... and ..............................due to external factors such as infection, toxin, or trauma.
cellular injury and premature death
53
What are the reasons of necrosis?
external factors such as infections, toxins, trauma
54
Main change in necrotic cell?
irreparable damage to the cellular membrane with subsequent leakage of cellular contents
55
Duchenne and Becker muscular dystrophies are caused by X-linked mutations to the ...................
dystrophin gene
56
Function of dystrophin?
Dystrophin provides mechanical stability to muscle cells during contraction.
57
Pathophysiology when dystrophin gene mutations?
Mutations are associated with membrane tears that allow calcium to enter the cell and cause myofiber damage
58
What happens to the cell when telomers shorten beyond a certain point?
the cell undergoes apoptosis or senescence
59
Reprogramming of undifferentiated mesenchymal cells (eg, connective tissue) is a form of ........................
Metaplasia
60
........................................(eg, connective tissue) is a form of metaplasia
Reprogramming of undifferentiated mesenchymal cells
61
Acid phosphatase is found in the ..............................
lysosomes
62
What does acid phosphatase?
hydrolyzes organic phosphates
63
guanylate cyclase plays important role in .......................... and ........................... of ................... (eg ........... and ....................)
activation and regulation of diverse physiologic processes (eg smooth muscle relaxation, retinal phototransduction)
64
What secondary signal is in smooth muscle relaxation and retinal phototransduction?
guanylate cyclase
65
Apoptosis is a means of carefully regulated cell death in which the cell activates .......................
enzymes to degrade its own nuclear DNA and proteins
66
What is the membrane condition in apoptosis?
it is intact
67
Why there are no inflammation in apoptosis?
because no cell contents are leaked into the surrounding tissue
68
What are the apoptosis phases? (2)
initiation and execution
69
What happens in initiation phase in apoptosis?
protein-hydrolyzing caspases are activated
70
What happens in execution phase in apoptosis?
caspases bring about the cell death by cleaving cellular proteins and activating DNAses
71
protein-hydrolyzing caspases are activated in ............ phase
initiation
72
caspases bring about the cell death by cleaving cellular proteins and activating DNAses in .............. phase
execution
73
The initiation of apoptosis occurs via signals from ..................................
two separate pathways
74
What are 2 pathways that initiate apoptosis?
intrinsic (mitochondrial) and extrinsic (dead receptor)
75
In the intrinsic pathway, the mitochondria become more ....................... and it leads to release of ............................ into....................
permeable; pro-apoptotic substances; into cytoplasm
76
Release of pro-apoptotic substances in intrinsic pathway in apoptosis happens in response to ....................................... (2)
in response to stress or the cessation of survival signal
77
Where reside anti-apoptotic proteins?
in mitochondrial membranes and cytoplasm
78
What are anti-apoptotic proteins?
Bcl-2 and Bcl-x
79
When anti-apoptotic proteins are replaced by pro-apoptotic proteins?
When cell is exposed to stress or the cessation of survival signals
80
What are pro-apoptotic proteins?
Bak, Bax, Bim
81
What cause pro-apoptotic proteins?
The pro-apoptotic proteins allow for the increased permeability of the mitochondria, which results in the release of caspase-activating substances like cytochrome c.
82
What is released when pro-apoptotic proteins replace anti-apoptotic proteins?
due to incr. mitochondria permeability - release of caspase-activating substances
83
What is the key enzyme in apoptosis?
caspases
84
What can activate caspases?
cytochrome c
85
Where occur death receptors in apoptosis?
in the cell surface
86
To what family belongs death receptors?
tumor necrosis factor receptor family
87
What are 2 best known death receptors?
type 1 TNF receptor (TNFR1) and Fas (CD95)
88
What is FADD?
death-domain containing adapter protein
89
What happens when Fas cross-links with its ligands?
multiple molecules of Fas come together to form a binding site for FADD
90
What happens when FADD binds Fas formed binding site?
FADD then binds an inactive form of a caspase, again bringing multiple caspase proteins together that through a cascade effect eventually induce caspase activation.
91
Hemosiderin accumulation is common in patients who have ..................... or .........................
hemolytic anemia or who undergo frequent blood transfusions
92
Chronic inflammatory conditions are characterized by the persistent stimulation of ........................................ (2)
Neutrophils and macrophages
93
Persistent stimulation of neutrophils and macrophages in chronic inflammation leads to increase of .............. (4)
Inflammatory cytokines such IL-1, IL-6, TNF and INF-gamma
94
What are 2 important acute phase reactants?
fibrinogen and globulins (CRP)
95
What influence has acute phase reactants on RBCs?
they cause RBCs to overcome their zeta potential (negative potential that separates them) --> rouleaux formation --> it is heavier than separate RBCs --> settle to the bottom of tube more quickly
96
Etiology of fibrinoid necrosis?
Malignant hypertension, vasculitis
97
Etiology of fat necrosis?
Acute pancreatitis, trauma (subcutaneous adipose tissue)
98
Etiology of liquefactive necrosis?
CNS infarcts, severe bacterial infection (eg gangrene)
99
Etiology of caseous necrosis?
```
Mycobacterial infection
Fungal infections (histoplasma, cryptococcus, coccidioides)
```
100
Etiology of coagulative necrosis?
irreversible ischemic damage outside CNS
101
Difference between apoptosis and necrosis?
apoptosis - no membrane damage.
| necrosis - loss of membrane integrity --> proinflammatory intracellular material leaks --> injury of surrounding tissue
102
Necrosis is an uncontrolled process of cell death that results in ........................ of cellular proteins and ......................... of cellular components
denaturation;
| enzymatic digestion
103
In most organs, irreversible ischemic injury typically results in .............................. (what necrosis?)
coagulative necrosis
104
Why in coagulative necrosis is maintained cellular architecture?
digestive enzymes denaturate before they destroyed cellular architecture, but nuclei are absent.
105
How differs liquefactive necrosis and coagulative?
in coagulative - maintaines cellular architecture;
| in CNS liquefactive - digestion of cellular constitutienst and liquefaction of necrotic tissue
106
In what areas occurs fat necrosis?
in tissues with high numbers of adipocytes (pancreas, breast, subcutaneous fat)
107
in fat necrosis: TG --> free fatty acids. What 2 factors cause this reactions?
active enzymes (eg lipases) or mechanical damage
108
From where occurs enzymes in fat necrosis?
enzymes are released from damaged cells
109
What combines with free fatty acids in fat necrosis?
it combines with calcium = saponification (calky-white deposits)
110
What is seen under microscopy in fat necrosis?
anucleated adipocytes with calcium deposits
111
what cells surround in caseous necrosis?
epithelioid macrophages and giant cells
112
How is described material in the centre of granuloma? it is made of ..........
white, friable, cheese-like material. it is made up of CELL FRAGMENTS AND AMORPHOUS PROTEINACEOUS DEBRIS
113
Why tissue architecture is preserved in coagulative necrosis?
Due to early denaturation of lytic enzymes
114
2 microscopic changes in coagulative necrosis?
Cells are nucleated with eosinophilic cytoplasm.
| Leukocytes eventually infitlrate and digest necrotic tissue
115
What immune cells digest necrotic tissue in coagulative necrosis?
Leukocytes
116
Fibrinoid necrosis results from ..................... (2)
Immune complex and/or plasma proteins (eg fibrin) that leak through the damaged intima and depositing within the vessel wall.
117
How appear deposits in fibrinoid necrosis in histology?
circumferential ring of pink, amorphous material surrounding the vascular lumen. (proteinaceous material - nes leakina baltymai eg fibrin)
118
How looks liquefactive necrosis?
infected abscess fluid is creamy yeallow due to dead leukocytes (pus)
119
why abscess is yellow in liquefactive necrosis?
due to dead leukocytes (pus)
120
How resolves brain infarcts?
it resolves into CSF-filled space
121
Why occurs dystrophic calcification?
Dystrophic calcification occurs in areas of tissue injury or necrosis that escape removal by phagocytes
122
What binds calcium in dystrophic calcification?
Phosphate ions bins calcium --> salts, which appear as white granules.
123
How microscopically occurs dystrophic calcification?
amorphous, basophilic material on H&E stain
124
How long it takes for dystrophic calcification to develop?
slowly - months and years following injury
125
What type of necrosis in in kidney and heart?
coagulative
126
Why there is not maintained cell architecture in brains in ischemia?
because there is lack of supporting architecture.
127
How long it takes to manifest for liquefactive necrosis in brains?
it occurs within 10 days oof infarction
128
What cells digest infarcted CNS tissue?
microglia (CNS macrophages)
129
What replaces digested CNS tissue?
cystic space surrounded by astroglial scar (gliosis)
130
How long it takes to form a cystic space + gliosis in CNS infarction?
months to years
131
Fibrinoid necrosis. What material accumulates?
Accumulation of fibrin-like material in the walls of blood vessels
132
fibrinoid necrosis in cerebral arteries can predispose a .........................
hemorrhagic stroke
133
What immune cells can be seen in fibrinoid necrosis?
neutrophilic infiltrates
134
tuberculosis infection in CNS. Acute or chronic?
Chronic
135
fat necrosis. What cells engulf what?
foamy macrophages contains engulfed lipids debris + release free fatty acids that combine with calcium.
136
free fatty acids combine with calcium and form deposits. They are eosinophilic or basophilic?
basophilic
137
Coagulative necrosis occurs following ..................
hypoxic cell death
138
Wound healing process needed to .... (2)
restore continuity and tensile strength.
139
4 stages of wound healing.
4 sequential (but overlapping) phases: hemostasis, inflammation, proliferation, and maturation.
140
What phase occurs immediately after tissue injury?
hemostasis
141
What is involved in hemostasis? (3)
small vessel constriction;
platelet aggregation;
clotting cascade activation;
142
Result of hemostasis? (3)
platelet plugging, fibrin clot formation, and cessation of bleeding
143
For relatively minor injuries, hemostasis is often accomplished within ................
minutes
144
The fibrin clot that is formed during hemostasis provides a ..................
scaffold for subsequent wound healing
145
inflammation after wound injury usually starts within ........................
hours of injury
146
What cells primary participate in inflammation phase?
mast cells --> degranulate --> vascular permeability + CELLULAR INFILTRATION (neutrophil, monocytes)
147
Function of neutrophils in inflammation phase?
digest bacteria, necrotic tissue and foreign debris
148
Function of monocytes in inflammation phase?
secrete growth factors (TGF-beta, VEGF, IL-1, TNF-alpha) --> promote next phase of healing
149
what 2 factors released from platelets in hemostasis phase?
PDGF, TGF-beta
150
PDGF from hemostasis phase induces ........ in inflammation phase.
macrophages
151
What factor from hemostasis activates macrophages in inflammation phase?
PDGF
152
TGF-beta from inflammation phase induces ........ in proliferation phase.
fibroblasts
153
What factor from inflammation activates macrophages in proliferation phase?
TGF-beta
154
Proliferation, which begins during the ..........phase and continues for ...........afterward
inflammatory phase and continues for weeks afterwar
155
3 processes that happens in proliferation phase?
epithelization, fibroplasia, angiogenesis
156
What happens in epithelization?
Basal keratinocyte proliferation and migration of new epithelial cells form a new superficial epithelial layer that acts as a barrier to bacteria.
157
what happens in fibroplasia?
Fibroblasts proliferate and synthesize ground substance and collagen, forming a matrix into which capillaries can grow
158
What process during fibroplasia help to decrease wound size?
Simultaneous contraction of myofibroblasts (ie, differentiated fibroblasts that produce contractile proteins) helps decrease the wound size.
159
What important proteins produce fibroblasts during fibroplasia?
differentiated fibroblasts that produce contractile proteins
160
What happens in angiogenesis?
Proliferation and migration of endothelial cells from nearby blood vessels lead to ingrowth of new capillaries into the collagen matrix.
161
Proliferate and migration of what cells happens in angiogenesis in proliferation phase? From where those cells migrate?
Endothelial cells;
| nearby blood vessels
162
Matrix in fibroplasia is formed from .............
collagen (collagen matrix - here can grow new capillaries)
163
The last phase of wound healing?
maturation
164
What happens in maturation phase?
collagen remodeling and cross-linking
165
the primary mechanisms by which the tensile strength of the wound increases?
collagen remodeling and cross-linking
166
duration of hemostasis?
0 hours-1 day
167
duration of inflammation?
3 hours- 5 days
168
duration of proliferation?
3 days - 5 weeks
169
duration of remodeling?
3 weeks - 2 years
170
What factors are produced by fibroblasts in proliferation phase?
FGF, VEGF, extracellular matrix
171
What enzymes plays a role in remodeling?
matrix metalloproteinases
172
What types of collagen in remodeling?
type III --> type I
173
hemostasis. 2 results?
vasoconstriction;
| fibrin clot formation
174
Inflammation. 3 results?
vasodilation;
incr. permeability;
inflmmatory cells chemotaxis
175
Recurrent respiratory infections + dextrocardia --?
Kartagner syndrome
176
Kartagner syndrome is a form of ..................
primary ciliaryy dyskinesia (PCD)
177
Inheritance of Kartagner syndrome?
autosomal recessive
178
Eukaryotic flagella and cilia are composed of ............
central core known as the axoneme
179
the axoneme is anchored to the cell by a ....................
basal body
180
The axoneme of flagella and motile cilia consists of a ............
a circular array of microtubule doublets surrounding 2 central microtubules (9+2 arrangement
181
Each doublet in cilia has an .............. and ...........subunits which are connected to ....................
Each doublet has an A and B subunit and is connected to the adjacent doublet via dynein arms.
182
These dynein arms contain an ............. that generates energy to slide the microtubules past each other, producing ciliary movement
ATPase
183
how happens ciliary movement?
These dynein arms contain an ATPase that generates energy to slide the microtubules past each other, producing ciliary movement.
184
Primary ciliary dyskinesia can result from failure of the ................. to develop normally.
dynein arms
185
Why patients with PCD experience recurrent respiratory infections?
due to impaired mucociliary clearance
186
What cardio pathology seen on xray in kartagner syndrome (PCD)?
dextrocardia
187
impaired ciliary movement during embryogenesis can cause ................
situs inversus (reversed right/left positioning of internal organs).
188
genital manifestation in PCD in women and men?
Infertility in men (impaired sperm motility) and women (immobility of fallopian tube cilia)
189
Deficiency of the C1 complement component causes increased susceptibility to ................... bacteria and also predisposes to developing ...........................
```
encapsulated bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis);
SLE
```
190
Same manifestation in PCD and cystic fibrosis?
recurrent respiratory infections, infertility;
| in PCD - sinus inversus (in cystic is not seen)
191
Epithelial cell chloride channels are defective in ...................
cystic fibrosis
