Block A Flashcards
(327 cards)
1
Q
4 subunits that can make intermediate filaments
A
keratin, laminin, neurofilaments, and vimentin
2
Q
up to ____% of protein in cell is actin
A
20
3
Q
Actin filaments require 3 things for polymerization
A
K+, Mg2+ and ATP
4
Q
cut actin filaments are called
A
gelsolin
5
Q
an actin capping protein
A
tropomodulin
6
Q
an actin cross-linking protein
A
spectrin
7
Q
are intermediate filaments polar?
A
no
8
Q
Keratins have highly conserved ____ domain and highly variable _____ domain
A
globular (terminal)
central
9
Q
most abundant IF
A
vimentin
10
Q
IF protein mostly found in muscle
A
desmin
11
Q
keratins will span the cytoplasm of _____ cells
A
epithelial
12
Q
Microtubules are a circle composed of ____ alpha/beta tubulin dimers
A
13
13
Q
formation of microtubule at MTOC is characterized by the presence of ____ tubulin
A
gamma
14
Q
____ tubulin is at the minus end of a microtubule
___ tubulin is at the positive end
A
alpha
beta
15
Q
do minus end of microtubules grow?
A
no
16
Q
microtubule remodeling is linked to a pattern of ___ hydrolysis
A
GTP
17
Q
all microtubules can be disassemble by
A
putting them in the cold
18
Q
proteins responsible for transport along microtubule track
A
molecular motor proteins
19
Q
molecular motor protein that moves toward minus end of microtube
A
dynein
20
Q
molecular motor protein that moves toward plus end of microtube
A
kinesin
21
Q
centrioles are built from what subunits
A
9 microtubule triplets
22
Q
keratin IFs can connect with the keratins of other cells via
A
desmosomes
23
Q
IFs form ________ filaments (only 1 type of protein)
A
homopolymeric
24
Q
easiest way to distinguish between centriole and cilia
A
cilia has doublet in middle
25
each cilium requires a ____ as its organizing center
basal body
26
basal body is formed by:
repeated replications of the centrioles and their migration to the apical surface
27
during mitosis, _____ microtubules are formed around each centriole. they are crucial for alignment of the mitotic spindle
astral
28
Centrosome cycle-
| Describe disengagement, duplication, engagement, maturation, and separation.
Disengagement- 2 centrioles break up, but are still tethered
duplication- each centriole makes a new centriole
engagement- new centrioles mature and the mother/daughter centrioles detach from each other
maturation- 2 individual centrosomes now mature and collect raw materials
separation- 2 centrosomes make spindle fibers between themselves
29
astral microtubules assure that:
centrioles are oriented properly
30
polar microtubules do what?`
help push dividing cells apart
31
colchicine-
prevent microtubule polymerization and also depolymerize microtubules.
32
what non cancer use does colchicine have?
treats gout
33
vincristine-
inibits spindle formation
34
taxol-
stabilizes and prevents depolymerization of microtubules
35
Cytochalasin B & D
disrupts actin microfilament and activates the p53 dependent pathways
36
lipofuscin-
brownish gold pigment seen in H&E preps. conglomerate of lipids, metals, and organic molecules. sign of cellular stress
37
lipofuscin is often seen in
neurons
38
hemosiderin is seen often where?
where there is red blood cell destruction (like spleen)
39
crystalline inclusions are often seen in _____ cells
sertoli and leydig cells of the testis
40
the five basic histone proteins
H1, H2A, H2B, H3, H4
41
nuclear lamins are in what class?
intermediate filaments
42
nucleolus stains intensely with what chemical?
hematoxylin
43
fibrillar centers-
contain DNA of 5 chromosomes (13, 14, 15, 21, 22), RNA polymerase I and transcription factors
44
fibrillar material (pars fibrosa)-
contains ribosomal genes actively undergoing transcription and large amounts of rRNA
45
granular material-
site of initial ribosome assembly
46
nuclear pores are _____ nm in diameter
70-80
47
nuclear pores contain about ___ different proteins
50
48
nuclear pores are cytoplasmic rings with protruding ______
protein fibrils
49
_____ and _____ fibers form in prophase
astral and spindle
50
nuclear envelope is broken down in _______
prometaphase
51
3 ways cells can proceed from mitotic arrest:
spindle depolarizes, apoptosis, or misaligned chromosomes realign
52
mitotic checkpoint is after
metaphase
53
Leptotene -
condensation of the chromatin and sister chromatids are paired to each other.
54
Zygotene -
close association of the homologous chromosomes (synapsis) by the formation of the synaptonemal complex.
55
Pachytene -
crossing-over (recombination)
56
Diplotene -
synaptonemal complex dissolves; chiasmata (junctions between homologous chromosomes) seen
57
Diakinesis -
homolog chromos condense, shorten, nucleolus disappears and the nuclear envelope dissolves
58
glycocalyx-
surface molecules that establish extracellular microenvironment. have receptors and enzymatic activity
59
P-face in freeze fracture
internal face, looks bumpy
60
linker proteins-
anchor extracellular matrix to intracellular cytoskeleton
61
phagocytosis requires rearrangement of:
actin cytoskeleton
62
does phagocytosis use clathrin?
no
63
adaptin is involved in
endocytosis
64
familial hypercholesterolemia-
defect in receptor prevents initiation of receptor-mediated edocytosis of protein-bound cholesterol
65
pH of early endosomes
slightly basic
66
late endosomes pH
acidic
67
multivesicular bodies-
transport substances between early and late endosomes
68
chaperone-mediated direct transport-
selective interaction of particles to be degraded with heat shock chaperone protein and its subsequent transport to lysosome
69
tay sachs disease-
missing enzymes to break down lysosomes, so lysosomes accumulate. first acts on neurons
70
Krabbe disease-
lysosome causes problems with myelin sheath
71
can genes of the nucleus influence mitochondria?
yes
72
mitochondria are important in the initiation of _____ after sensing cell stress
apoptosis
73
3 enzymes in outer mitochondrial membrane-
PLC A2, monoamine oxidase, acetyl CoA synthase
74
3 enzymes in intermembrane space of mitochondria
creatine kinase, adenylate kinase, and cytochrome C
75
cytochrome C initiates-
apoptosis
76
Zellweger syndrome-
inability to import proteins into the peroxisome, leads to early death because perxisomes lack the necessary enzymes
77
Pyronin G stain color
red
78
Acid fuchsin stain color
red
79
eosin stain color
red
80
H&E most darkly stains what material?
genetic
81
PAS stands for
periodic acid schiff
82
PAS best stains what molecules?
carbs
83
actin bundles from microvilli extend down into apical cytoplasm and form the _____ with ______
terminal web with intermediate filaments
84
Structure of cilia
made of microtubules in a 9+2 configuration
85
axoneme-
microtubule based internal structure of motile cilia
86
_____ generates the sliding force in axonemes
dynein
87
are primary cilia motile?
no
88
what is the structure of primary cilia
9+0
89
primary ciliary dyskinesia
lack of dyneisn proteins, no motion
90
stereocilia are actually
microvilli
91
tight junctions are near the ____ surface of epithelial cells
apical
92
hemidesmosomes anchor ___ to ____
IF to ECM
93
basement membrane =
basal lamina + reticular lamina
94
basal lamina is composed of (4)
laminins, collagens, proteoglycans, and glycoproteins
95
epidermolytic hyperkeratosis-
excessive keratinization causes breakdown of epidermis
96
merocrine secretion-
secretory product in membrane bound vesicles
97
apocrine secretion-
large secretion released in the apical portion of the cell
98
holocrine secretion-
whole cell fills with secretion, which is released when cell dies
99
hydration is a function of _______ tissue
connective
100
mesenchymal stem cells are derived from
epiblast
101
mesenchymal stem cells are precursors to other cell types, including
mesoderm and CT
102
mucous CT has a _____ appearance
stellate/star like
103
mucous CT nuclei have a _____ shape
pyramidal
104
mucus CT nuclei appear euchromatic or heterochromatic?
heterochromatic
105
mucous CT contains ground substance called
whartons jelly
106
_____ are the primary cell type of CT
fibroblasts
107
loose CT is known as
areolar tissue
108
loose CT is sparse in _____ and abundant in _____
collagen/elastin
| ground substance
109
LCT provides structural support to what tissues
fragile tissues like capillaries
110
basal lamina is secreted by:
overlying epithelial cells
111
LCT synthesizes _____ which resides below basal lamina
reticular lamina
112
reticular lamina is composed of _____ fibers
collagen
113
dense irregular CT has much more ___ than LCT
collagen
114
Dense regular CT has much more ____ than LCT
collagen
115
nuclei of DRCT appear:
squished in between collagen fibers
116
DRCT has good or poor vascularization?
poor
117
what type of CT makes up ligaments, tendons
DRCT
118
nuclei of DRCT as opposed to skeletal muscle
nuclei of DRCT are more squeezed/linear
119
tendinocyte process-
wraps around collagen fiber and is important in maintaining the fibers and recycling/replacing them when called for
120
how to differentiate btw LCT and DCT?
LCT tends to line ducts
121
fibrillar matrix
ECM that cells suspend in to make up CT
122
composition of fibrillar matrix-
collagen, reticular (type 3) collagen, and elastin
123
structural organization of collagen: from large to small
fascia, tendons, ligaments--> collagen bundle--> collagen fiber--> collagen fibril--> packed collagen molecules--> collagen molecule--> amino acids
124
collagen is not connected end to end, rather the fibrils are ______
cross linked
125
if striations are seen on high power EM, you are probably looking at:
collagen fibril striations
126
Type 1 collagen is found in (7 places)
CT of skin, bone, tendon, dentin, sclera, fascia, and organ capsules.
127
Type 2 collagen found in (3 places)
cartilage (hyaline and elastic), the notochord, and IV disks
128
Type 2 collagen provides resistance to
intermittent pressure
129
Type 3 collagen is found in (6 places)
LCT, organs, smooth muscle, blood vessels, endoneurium, and fetal skin
130
Type 3 collagen forms _____ which are arranged as a loos mesh of thin fibers to provide a scaffold for specialized cells
reticular fibers
131
Type 4 collagen is found in (3 places)
basal lamina of epithelia, kidney glomeruli, lens capsules
132
type 4 collagen provides support and a _____ barrier
filtration
133
________ collagens are resistant to tensile force and capable of regulating other collagen molecules
fibrillar
134
Collagen types __ and ___ are fibrillar
1 and 3
135
FACITs
fibril associated collagens with interrupted triple helixes
136
collagen molecules are arranged as a _____ helix
triple
137
Type ____ collagen is an example of a FACIT
IX
138
Type IX collagen stabilizes networks of Type II collagen fibers to produce ______
hyaline cartilage
139
FACITs are usually associated on:
the surface of other collagen fibrils
140
Hexagonal Network forming collagen-
developmental collagens (like at epiphyseal plate)
141
example of Hexagonal network forming collagen-
type X
142
transmembrane collagens-
interact with cell membrane and other extracellular matrix proteins
143
example of transmembrane collagen-
type XVII interacts with integrin to anchor hemidesmosomes
144
multiplexins and basement membrane forming collagens-
interact with the cell membrane and other ECM proteins
145
example of multiplex/basement membrane forming collagens-
Type VII collagen, which secures the basal lamina to the underlying type III collagen that compose the reticular lamina
146
during collagen synthesis, prepro-collagen undergoes ______ to render it unreactive to other rER contents
hydroxylation
147
collagen hydroxylation requires ______
vitamin C
148
hydroxylation is necessary for the formation of ____ bonds
H
149
_______ proteins prevent intracellular aggregation of collagen
chaperone
150
cleavage, alignment, and polymerization of collagen occurs where?
ECM
151
Type III/Reticular collagens are just like type 1 except
they are thinner and have more branching
152
Brittle bone syndrome-
osteogenesis imperfecta
153
collagen affected in osteogenesis imperfecta (fibrillar class)
type 1
154
Type 4 collagen disorder (fibrillar class)
Ehlers-danlos
155
Type X collagen disorder (Hexagonal network forming class)-
Schmid Metaphysal Dysplasia
156
Type XVII collagen disorder (Transmembrane class)-
Generalized Atrophic Benign Epidermolysis Bullosa (GABEB)
157
Elastic fibers are composed of what 2 types of fibers
elastin and fibrillin
158
elastic fibers are sythesized by
fibroblasts and smooth muscle cells
159
Type IX (facit class) collagen disorder
Multiple epiphyseal dysplasia
160
the backbone for ground substance-
hyaluronan
161
GAGs are attached to _____ which are attached to ______
core proteins
| hyaluronan
162
multiadhesive glycoproteins stabilize ______
ECM
163
Multiadhesive glycoproteins are associated with
basal lamina
164
myofibroblasts-
differentiated fibroblast (contractile and secretory)
165
anthracosis-
process where macrophages stain black from eating carbon
166
distinct feature of plasma cells-
have clock faced arrangement in their nuclei
167
type of cartilage made depends on the secretions of
chondrocytes
168
Type __ collagen is most common type found in cartilage
2
169
Hyaline cartilage is basically all cartilage except for which 2 places
ear, epiglottis, and IV discs
170
______ is dense connective tissue that surrounds hyaline cartilage
perichondrium
171
Hyaline cartilage matrix contains (6 things)
perichondrum, type 2 collagen, proteoglycans (protein core), GAGs, multiadhesive glycoproteins, and isogenic groups
172
2 types of GAGs
chondroitin and keratin sulfate
173
isogenic groups-
clusters of chondrocytes within cartilage derived from division of a single chondrocyte. Clustered in pairs or groups of 4
174
lacunae-
empty spaces due to prep (cell shrinkage usually)
175
Capsular matrix zone-
immediately surrounding chondrocyte (mostly type VI)
176
Territorial matrix zone-
contains type 2 cartilage, stains dark blue
177
interterritorial zone-
surrounds territorial matrix zone and occupies space btw groups of chondrocytes
178
Fibrocatilage contains which 2 collagens
type 1 and 2
179
fibrocartilage is located in:
IV discs
180
elastic cartilage contains type ___ collagen
2
181
_______ + ______ = elastic cartilage
hyaline cartilage + elastin
182
with silver stain, elastin appears as
black fibers
183
location of elastic cartilage
epiglottis and ear
184
elastic and hyaline cartilage are associated with a ______. fibrocartilage is not
perichondrum
185
appositional growth-
new cartilage forms on surface of existing cartilage
186
interstitial growth-
new cartilage forming within existing cartilage
187
what kind of stem cells can differentiate into fat cells?
mesenchymal stem cells
188
nuclei of white fat are where?
periphery
189
nuclei of brown fat are robust and located where?
not the periphery
190
_____ regulates appetite and body energy expenditure
leptin
191
_____ increases insulin resistance.
resistin
192
______ is linked to obesity and type 2 diabetes
resistin
193
non-muscle contractile cell in the seminiferous tubules
myoid cells
194
3 common non-muscle contractile cells
myoepithelial, myofibroblasts, pericytes
195
myoepithelial cells stain how?
brightly red
196
visceral striated muscle-
basically skeletal muscle not attached to bones (its in esophagus)
197
list the hierarchy of muscle from smallest to biggest, starting with myofibers
myofilaments--> myofibrils--> myofibers-->fascicle--> muscle
198
______ carries blood supply, innervation, and lymphatics that supply blood vessels
perimysium
199
perimysium surrounds:
fascicles
200
within each myofiber, myofibrils are suspended in the
sarcoplasm
201
where are fibroblast nuclei located
extracellularly, outside of muscle cells
202
Red fibers undergo _____ as main energy source
oxidative phosphorylation
203
white fibers undergo ____ as main energy source
glycolysis
204
sarcomere is defined as distance between
adjacent Z lines
205
length of a sarcomere ranges from ___ to ___
1.5-2.5 um
206
Terminal Cisternae of Junctional Sarcoplasmic Reticulum-
tube-like structures at A/I junction that serve as the reservoir for storage of Calcium outside of the cytoplasm but in the SR
207
Transverse tubule invaginates at site where:
A and I bands overlap
208
Triad is at the site of the _____ junction in muscle cells
A-I
209
Triad = _____+_____
1 Transverse Tubule + 2 Terminal Cisternae
210
how many triads per sarcomere?
2
211
in the terminal cisternae, calcium binds to:
calsequestrin
212
nonjunctional SR appears as:
squiggly lines running transversely between triads
213
Accessory proteins of the thin filament
tropomyosin, tropomodulin, troponin complex
214
list the components of the troponin complex (3)
TnT, TnC, TnI
215
tropomyosin lies where?
in the groove on F-actin
216
tropomodulin does what?
binds both F-actin and Tropomyosin
217
when calcium binds to TnC, ______ moves to expose active site
tropomyosin
218
each myosin has a tail with ___ chains, and a head with _____ chains.
2 heavy
| 4 light
219
+ end of actin filament faces:
Z line
220
Z line is made of
alpha-actinin
221
M line is made of:
C protein and myomesin
222
what do proteins on M line do?
they stabilize the sarcomere through interactions with thick filaments
223
Titin-
protein taht anchors thick filament to Z line
224
Nebulin-
protein that anchors thin filament to Z line
225
how does nebulin attach to thin filament?
spirals around it
226
5 stages of muscle contraction cycle:
attachment, release, bending, force generation, and reattachment
227
describe muscle contraction stage 1
Attachment. rigor. Myosin is bound to actin in bent position
228
describe muscle contraction stage 2
release. ATP binds to myosin head. Myosin is released from actin
229
describe muscle contraction stage 3
bending. ATP hydrolysis cocks myosin head
230
describe muscle contraction stage 4
force generation. phosphate is released, causing myosin to bind to actin and power stroke. then ADP is released.
231
describe muscle contraction stage 5
reattachment. rigor again
232
terminal branches of axon contact muscle fiber at the _______ of the neuromuscular junction
motor end plate
233
motor unit
a single motor neuron and the muscle fibers that it innervates
234
junctional folds-
finger like projections coming up from muscle cell in synaptic cleft
235
external/basal lamina around neuromuscular junction produce what enzyme?
acetylcholinesterase
236
muscle spindle apparatus-
sensing unit of muscle that responds to stretch. stretching in morning fine tunes this apparatus
237
muscle spindle apparatus contains what kind of nerve fibers?
afferent and efferent
238
muscle spindle apparatus is inserted inside
middle of muscle fiber
239
nuclear bag fibers-
cells with central collection of nuclei
240
nuclear chain fibers-
cells with linear arrangement of nuclei
241
intrafusal fibers-
modified striated muscle fibers within the spindle apparatus
242
extrafusal fibers-
normal muscle fibers outside of the spindle apparatus
243
Golgi tendon organ contains what kind of nerve fibers?
afferent only
244
which component of proprioception has both afferent and efferent nerve fibers?
muscle spindle apparatus
245
what component of proprioception has only afferent fibers?
golgi tendon organ
246
golgi tendon organ detects
contraction
247
3 cardiac muscle cell types-
atrial cardiomyocytes, ventricular cardiomyocytes, purkinje fibers
248
ventricular cardiomyocytes mostly have how many nuclei?
2
249
cardiac muscle cells are not fused like skeletal muscle, but they do function as a:
synctium
250
how does size of cardiac transverse tubules compare to skeletal muscle?
they are larger
251
Where is calcium stored in cardiac muscle?
T tubules
252
_____+______= dyad in cardiovascular muscle
1 TT + 1 SR
253
Fascia adherens-
broader areas of tight connections with IF, only found in heart intercalated discs
254
2 things in lateral component of intercalated discs-
macula adherens and gap junctions
255
fusiform-
football shape of smooth muscle cells
256
what stores calcium in smooth muscle?
caveolae
257
calcium is bound to _____ in smooth muscle
calmodulin
258
smooth muscle cells communicate via
gap junctions
259
what anchors IF and myofibrils in smooth muscle?
dense bodies
260
dense bodies are similar to ______ in skeletal muscle
z lines
261
smooth muscle myosin in relaxed state looks like?
golf club coiled into a hoop
262
______ is directly bound to dense bodies in SM
actin
263
instead of a bipolar thick filament, smooth muscle myosin is
side-polar thick filament. thick filaments are pulled in opposite directions
264
Describe the process of smooth muscle cell contraction, starting with depolarization/receptor binding.
either of the aforementioned methods will trigger calcium release, which will bind with calmodulin. this complex will then activate myosin light chain kinase, which will phosphorylate myosin light chains, which releases them from their looped configuration. the myosin is now active. phosphatases will dephosphorylate MLCK to inactivate muscle contraction
265
name 2 ways smooth muscle contraction is triggered
hormones or autonomic (depolarization)
266
some skeletal muscle regeneration can occur via _____ cells
satellite
267
amount of muscle in large vessels is high or low?
low
268
does tunica intima have smooth muscle?
sometimes
269
smooth muscle cells of tunica media can secrete
collagen and elastin
270
in disease processes, _________ break down in tunica media
collagen and elastin
271
nerve supply to tunica adventitia
nervi vascularis
272
blood supply to tunica adventitia
vasa vasorum
273
identifying layer of large arteries
large tunica media with alternating layers of smooth muscle cells and elastic tissue
274
what does tunica adventitia of arterioles look like?
thin and ill defined
275
endothelial cells of arteries are connected by
junctional complexe
276
what is condition of basal lamina in fenestrated capillaries?
still intact
277
neuron cell bodies are also referred to as
perikaryon
278
nissl bodies
stacks of rER and ribosomes asociated with cells undergoing lots of translation and protein synthesis
279
sympathetic chain ganglia nuclei are polarized, meaning they appear
shifted to one side due to large amounts of rER
280
branches of dendrites in purkinje cells are called
arborizations
281
3 types of dendrites
unencapsulated, encapsulated, and epithelial cell associated
282
pacinian corpuscles
encapsulated axon terminals that detect deep pressure
283
meissner's corpuscles
encapsulated axon terminals that detect light pressure
284
3 types of receptors associated with sensory neuron dendrites
exteroreceptors, enteroreceptors, and proprioceptors
285
________ establishes the blood-nerve barrier
perineurium
286
perineurium shares a common basal lamina with
the endothelial cells lining the lumen of blood vessels
287
kinesins participate in _____ transport
| dyneins participate in _______ transport
anterograde
| retrograde
288
nestin-
causes neurons to divide
289
electrical synapse gap junctions are called
connexins
290
terminal end of axon (chemical synapse) is called
synaptic bouton
291
majority of NT removal is via
reuptake
292
minority of NT removal is via
degradation
293
perent of lung that is solid tissue
10
294
surface area of lung
80-100 square meters
295
lungs inspire how many liters per day
10000
296
3 types of epithelium of nasal cavity
stratified squamous, and respiratory and olfactory pseudostratified columnar
297
olfactory mucosa =
epithelium + lamina propria
298
sustenacular cells-
columnar support cells
299
basal cells-
stem cells
300
brush cells-
general sensation cells
301
does olfactory epithelium have direct blood supply?
no, nutrients and O2 have to diffuse throughconnective tissue
302
5 cell types in respiratory epithelium
ciliated, mucous, basal, brush, and small granule
303
turbinates-
nasal conchae (nasal cavities) (increase surface area of nasal cavity)
304
basal bodies consist of a ________ microtubule arrangement of triplets
9+0
305
3 types of epithelium in larynx
stratified squamos, simple columnar, and pseudostratified columnar
306
where does respiratory epithelium change from ciliated pseudostrat columnar to stratified squamous?
at the larynx
307
4 layers of trachea
mucosa, submucosa, cartilaginous layer, and adventitia
308
BALT
bronchial-associated lymphatic tissue
309
MALT
mucosa associated lymphatic tissue
310
when primary bronchi branch into secondary bronchi, cartilaginous rings are replaced by
plates
311
as diameter of secondary bronchi decreases, amount of smooth muscle _______ and cartilaginous plates _______
increases
| decreases
312
secondary bronchi have what kind of epithelial cell?
pseudostratified columnar and simple columnar epithelium
313
what glands disappear in secondary bronchi?
submucosal glands
314
in what branches of airway do cartilage plates and submucosal glands disappear?
tertiary bronchioles
315
what respiratory segment do clara cells first show up in?
tertiary bronchioles
316
what kind of epithelial cells do tertiary bronchi have?
simple ciliated columnar epithelium
317
what kind of epithelial cells do terminal bronchioles have?
simple ciliated columnar or cuboidal epithelium
318
when do clara cells start to disappear?
in respiratory bronchioles
319
type 1 alveolar cell function
gas exchange
320
what kind of epithelium are type 1 alveolar cells?
very flat squamous cells
321
shape of type 2 alveolar cells?
cuboidal
322
where are type 2 alveolar cells found?
at septal junctions
323
which is more prolific, type 1 or 2 alveolar cells?
type 2
324
what plays a part in collateral ventilation in the alveoli?
Alveolar pores of Kohn
325
alveolar macrophages are also known as
dust cells
326
foreign body giant cell-
several macrophages that fuse together to encapsulate large particles
327
emphysema will lead to an increase in _____ tissue in the lungs
fibrotic
