Week 1 Cell Injury Flashcards
1
Q
continuously dividing cells
A
are stem cells
2
Q
exampled of continuously dividing cells
A
basal cells in epidermis, hemopoietic cells in the bone
3
Q
Quiescent or stable cells
A
develop into whatever cell they want to be and sits in G0 until need
4
Q
example of quiescent cells
A
liver cells, renal cells, smooth muscle cell, fibroblast
for example>liver transplant>loss a piece of liver> liver cells (leave out of G0) begin to divide again to recover parts that’s missing
5
Q
non-dividing cells (permanent cells)
A
cannot divide no more
6
Q
examples of non-dividing cells
A
neurons, heart cells
cells go through hypertrophy due to inability to divide again
7
Q
two types of stem cells
A
embryonic stem cells
tissue stem
8
Q
what does totipotent mean
A
develop into any cell they want
9
Q
what are growth factors
A
signal when cells need to divide
10
Q
where are the three check points in the cell cycle
A
G1, G2, M
11
Q
what occurs in G1 checkpoint
A
check to see if proteins are available for replication
12
Q
G2 checkpoint consist of
A
did replication go okay? no send into G0 (prepare for repair or apoptosis)
13
Q
M checkpoint
A
check to see if each chromosomes consist of spindles> chromosomes split correctly
14
Q
why are cyclins important
A
they also control if the cell can advance to the next stage
cyclins bind to kinase> causes phosphorylation> trigger translation/transcription
15
Q
what a cyclins removed by
A
proteasomes
16
Q
proto-oncogenes
A
normal gene coding for proteins
they tell cells when they need to grow (coding proteins)
17
Q
what happens when a proto-oncogene is mutated/or structure manipulated
A
creates and activates oncogenes>causes uncontrolled cell growth> POTENTIAL cancer/disease
18
Q
examples of proto-oncogenes mutated
A
HER2 gene (breast cancer)
BCR-ABL (chronic myeloid leukemia)
19
Q
explain BCR-ABL (proto-oncogene)
A
ABL1(proto-oncogene) gene on chromosome 9 breaks off> attaches to the BCR gene on chromosome 22>BCR-ABL1> CML
20
Q
HER2 gene pathway
A
HER2 (proto-oncogene)> mutated> b/c oncogenic> cancer
21
Q
tumor suppressor gene
A
loss of function
22
Q
what happens if TSG is mutated
A
TSG mutated> loss ability to stop damaged cell> cell continues to grow> cell build up > hyperplasia (>dysplasia> cancer)
most commonly known TSG is p53
23
Q
Retinoblastoma
A
cancer occuring in the eye usually young children
24
Q
explain what causes retinoblastomas
A
Rb gene(a type of TSG)> loss ability to block cell cycle progression>causes cancer due to uncontrollable cell growth
25
5 types of cellular growth adaptations
hyperplasia, hypertrophy, atrophy, metaplasia, dysplasia
26
hyperplasia
increase in NUMBER of cells
27
is physiological hyperplasia good?
yes
28
examples of physiological hyperplasia
1. breast during pregnancy (hyperplasia of mammary glands to help with breast feeding)
2. increase in thickness of endometrium during menstrual cycle
3.liver growth after partial resection( more hepatocytes to accommodate lose of partial liver)
29
examples of pathologic hyperplasia
menses that last for 2 weeks=increase in estrogen > increase number of endometrial cells> cause 2 week menses due to increasing shredding process
30
hypertrophy
increase in SIZE of the cell
31
examples of physiologic hypertrophy
weight lifting causing skeletal or cardiac muscle to grow
32
examples of pathological hypertrophy
LVH=increase in bp> cells work harder> cause cells to grow in cell.
33
atrophy
decrease in the size or number of cells
34
physiological atrophy examples
decrease in uterus size after birth
person who gets casted because of a broken bone> injured area sjrinks> atrophy> begin to use again> grows back
35
pathologic atrophy examples
loss of stimulus to the organ
-loss of endocrine stimulus(using steroids> increase cortisol w/o adrenal gland> AG atrophies due to no usage
-loss of blood supply or innervation
-aging
-inadequate nutrition/cachexia
-disuse, mechanical compression
36
Metaplasia
reversible change of epithelium at a site, or location, from one type of epithelium to another type. (cells are NORMAL but in a ABNORMAL LOCATION)
37
example of metaplasia
usually always pathological
Barretts Esophagus= esophageal squamous cells> not equip to handle acidic pH> TFG activate> columnar cells form to tolerate acidic pH
38
Dysplasia
usually not reversible
extremely disordered cell growth. nucleus different and irregular in size + cells are different sizes as well
39
examples of dysplasia
Pap smear> mostly reversible here> HPV> squamous cells displaced
-can go back normal if not its cut or burned out.> can cause cancer if not removed.
40
example of reversible cell injury
Decrease in O2>glucose> 2 pyruvate > release NAD+ and 2ATP > will creating lactic acid
2 ATP> causes hypoxia> ATPase pump isnt working effectively> decrease pH of the cell
41
reversible cell injury example
plaque in BV> decrease O2 in BS to heart> can cause ischemia if not treated>nitroglycerin added> relax and dilates BV> increase O2 in BS> muscles get O2
42
Irreversible cell injury examples
decrease O2 in BS to heart> cause ischemia> necrosis of the myocardial cells> cardiac biomarkers in blood elevate (troponin and ck-mb)
43
what are two important factors determining irreversible damage
membrane disturbances and irreversible mitochondrial dysfunction
44
hypoxemia
BLOOD level of O2 abnormal
45
hypoxia
low oxygen delivery to TISSUE
46
explain irreversible mitochondrial dysfunction
release (ROS)free radicals> ROS build up > damage DNA b/c nothing is neutralizing it> necrosis
47
how are free radicals generated
1. inflammation
2. UV light, xrays, and ionizing radiation
3. metals (iron, copper)
4. drugs and chemicals
48
what damage does free radicals cause
1. lipid peroxidation (damages cell membranes)
2. DNA fragmentation
3. protein cross-linking=results in increased degradation and decreased activity.
49
what can prevent free radical formation
1. antioxidants(vitamins)
2. metal carrier proteins- transferrin (iron), ceruloplasmin (copper)> can bond to free radicals
3. scavenger enzymes>reduce free radicals
-catalase-degrades hydrogen peroxide
-superoxide dismutase-which converts superoxide to hydrogen peroxide
-glutathione peroxidase-which catalyzes breakdown of hydroxyl radicals
50
what are two ways apoptosis is activated
intrinsic(inside cell) and extrinsic (outside source(old cell/ problematic cell)> cytotoxic T cells are alert)
51
apoptosis pathway
intrinsic/extrinsic> CASpase>activates destruction of cytoskeleton, DNA, organelles> form blob that form apoptotic bubble> macrophage eat it
52
can apoptosis be both physiologic and pathologic
yes, web fingers during child birth is an example of physiological
53
cellular senescence
aging
telemeres> protect end of chromosomes> shorten each cell division> gets super short and stop proliferating
54
senescence cells
cell can no longer divide> remains active> can release chemicals that can damage nearby cells (contribute to aging)
55
types of necrosis
coagulative, liquefactive, caseous, fat, fibrinous, gangrenous
56
coagulative meaning
example
caused by ischemia proteins denature>enzyme degrade
most common
cell dies but remains firm
ex. heart attacks
57
liquefactive meaning
example
cells break down and become soup like
neutrophils release lysosomal enzymes>degrade tissue> liquidy
ex. bacterial abscesses and brain infarcts
58
caseous meaning
example
liquid+coag=create cottage cheese appearance
ex. TB, systemic fungi
59
fat meaning
example
damage cells release lipase
ex. acute pancreatitis
60
fibrinoid meaning
example
shearing force/microtrauma from virus
fibrin develop in vascular wall causing damage
ex. COVID19, temporal arteritis
61
gangrenous meaning
example
dry gangrene mummified like tissue
wet gangrene-superimposed infection of tissues followed by liquefactive necrosis
ex. peripheral artery disease>black toes
gangrene.
62
what are the three categories of intracellular accumulations
normal cellular constituents(lipid, protein, glycogen, CHOs)>excess can be dangerous
abnormal substances(minerals, products of abnormal metabolism)
pigments/infections-tattos/bilirubin
63
calcium accumulation( metastatic vs dystrophic)
metastatic=widespread deposition on Ca2+ tissue via blood stream
Ex. Squamous cell small lung cancer >increase ca2 in blood stream from a tumor secreting PTH like hormone
dystrophic= localized Ca depostion in abnormal tissue/necrotic tissue
ex. calcification in the heart valves.
Aortic stenosis
arteriosclerosis
64
steatosis
fatty change> yellow discoloration of an organ
common in liver, kidney, heart, and skeletal
ex. fatty liver disease
65
protein accumulation ex.
sarcoidosis, amyloidosis(protein build up in organs and tissue), Alzheimer's Disease
66
explain the extrinsic apoptosis pathway
old cell/problematic cell>macrophage release TNFa or cytotoxic T cells expresses Fas protein>TNF or Fas binds death receptor> activate/formation of DISC (death inducing signaling complex)> activate CASPASES system
67
explain the intrinsic apoptosis pathway
radiation, ischemia, ROS> activation of BAX/BAK proteins that penetrate mitochondria> mitochondria releases cytochrome c > combines to other proteins and form apoptosome> activate caspases system
68
acute inflammation
fights quickly, innate response, Good response
69
chronic inflammation
adaptive response, tissue injury>disease basically the bad response
70
what causes cellular injury
hypoxia/ischemia/necrosis
physical agents/trauma
genetic derangements
foreign bodies
nutritional
chemicals/drugs
infectious agents
immune mediated
71
cardinal signs of inflammation
rubor(redness)
dolor(pain)
calor (heat)
tumor (swelling)
functio laesa (loss of function)
72
what are the 5 Rs of acute inflammation(in order)
1. recognition
2. recruitment
3. removal
4. regulation
5. repair
73
explain step one of acute inflammation (recognition)
TLRs on macrophage or mast cells identify DAMP/PAMP
74
what do PAMP identify
pathogen/bacteria on membrane wall/wall components
75
what does DAMP identify
damaged or dying cells..
76
explain step 2 of acute inflammation
2.recruitment
cytokines released from mast and macrophages> causes vasodilation +permeability >allows PMN (neutrophils) to arrive to scene(follow cytokines trail)
77
what cytokines do macrophages release
IL-1,TNFa, (IL-6)
78
what cytokines do mast cells release
histamines, serotonin, prostaglandin, eicosanoids
79
what causes Nitrous Oxide release
release of cytokines (IL-1/IL-6)> acts on endothelial cells>release NO
80
what causes (rubor) redness and warmth (Calor)
histamines, prostaglandin, serotonin
81
what happens in stage 3 of acute inflammation
3. removal
-neutrophils (PMNs engulf pathogens/damaged cells (intracellularly using lysosomes)
-or they use oxidative burst (complement system) which causes destruction
82
what stage causes tumor? and what is tumor?
Swelling and edema
caused by neutrophils rushing to the area and engulfing the cells or oxidative burst..
83
whats stage 4 of acute inflammation
4. regulation
macrophages sense resolution>release(increase) IL-10, TGFb and lipoxines> slow down inflam. response
84
what is stage 5 of inflammation
Repair
Macrophages secrete VEGF(vascular blood cell), TGF (tissue growth factor), Fibroblast, and EGF (epithelial growth factor).
85
where else do cytokines travel to outside of the blood stream
They travel to the liver and release: ESR, CRP, Ferritin, Fibrinogen, Hepcidin, IL-6 which helps indicate that their is an injury/inflammation
86
What is ESR
Erythrocyte Sedimentation Rate (ESR)- how quickly they clump(aggregate)...increase in pathogens=longer to clump
87
what is CRP
C-reactive protein...inflammatory marker
88
what does ferritin levels mean
store iron...increase in iron storage because bacteria needs iron to survive> therefore ferritin helps store iron in liver
89
what does fibrinogen levels mean
vascular injury>normally leads to clotting
90
what does hepcidin levels mean
trigger the iron storage in liver=decrease iron absorption
91
IL-6
cytokine therefore is going to be upregulated because of inflammation
92
how does a fever occur in the body?(during inflammation)
cytokines release IL-1 and TNFa in bloodstream >go to hypothalamus>release PGE2>act on receptors on hypothalamus>cause set point to increase> fever> hypothalamus signals sympathetic system> bv vasoconstrict> shiver > to keep heat in the body to raise temp.
93
how does tylenol (acetaminophen/NSAIDs) treat fevers
inhibits COX which stops the formation of prostaglandin
94
hyperthermia pathway
outside in heat> body temp increase> sweating> vasodilation> heat release> sweat evaporates>vaporize>endothermic reaction
BUT if you arent hydrated=cant sweat>causes hyperthermia..
95
what are the 5 outcomes to acute inflammation
resolution(complete resolution)
abscess
scar formation
96
abscess
macrophages unable to get rid of bacteria> repair/scar around the infection> causes pain, fever, can rupture and swelling
usually filled with pus (MRSA)=from macrophages eating and degenerating the bacteria
97
scar formation
ex. burn> kills basal cells> cant make new skin> fibrin/collagen deposits> scar tissue
loss of cells that are capable to regenerate causes collagen placement
98
what are two outcomes of chronic inflammation
ulcer, fistula
99
ulcer
ex: H.pylori... long term use in NSAIDs>block prostaglandin>causing decrease in PG> weaken stomach lining> ulcers
cause pain, hemorrhaging if near vessel, perforation
body unable to rid itself of an inciting agent (NSAIDs blocking prostaglandin)
100
Fistula
connection between two organs.
ex: inflammatory bowel disease (Crohn's) >inflamed lining> macrophages sense abnormal>keep inflaming> makes fibrin/collagen> attaches to another organ> seal it off (fibrin/collagen)
helps with draining of inflammation
101
what is healing
regeneration of cells combined with scarring and fibrosis. no stem cells
102
healing by first intent
healing of surgical sutures
clean cut, clean edges, close approx marginals
small non existent scar
103
healing by second intention
dog bite> basal layer is gone> cant stitch back
unclean edges, extensice tissue disruption, tissue necrosis
104
what is chronic inflammation
prolonged inflammation..active inflammation and tissue repair and destruction happening together
105
causes of chronic inflammation
viral, persistent, microbial infection, prolonged exposure to toxin, autoimmune dysfunction
TB, Syphilis, autoimmune disease
106
mediators of chronic inflam.
macrophages, T-cells B cell (plasma cells)
107
outcomes of chronic inflam.
scarring
amyloidosis (deposition of misfolded proteins)
granulomatous
neoplastic transformation (mutations)
osteomyelitis (knee arthritis> macrophages stay in knee> continuous tear of joints
rheumatoid arthritis
chronic peptic ulcer
tuberculosis
cardiovascular disease
ulcerative colitis
108
how does IL1 contribute to chronic inflammation
IL1 increase> chronic inflam.> chronic disease
109
importance of NFkB related inflammatory
when cytokines are released> activate NFkB > lead to inflammation
gene increases with age
IL1 is a NFkB
110
granulomatous inflammation
inflammation due to persistent T cell activation by infection, foreign body
granulomas-wall off stimulus without completely degrading it=macrophages surround the wound by secreting fibrin
111
two types of granulomatous
caseating= central necrosis (cheesy bc macrophage eats it)
non-caseating= no central necrosis=macrophages and fibrin clutter (normally caused by autoimmune or inflamed by foreign body)
112
examples of granulomatous inflammation
Non caseating:
-sarcoidosis
-foreign bodies, parasites
-silicosis
Caseating:
-TB (trying to contain disease)
