Unit IV Week 1 Flashcards
1
Q
Fusion in mitochondria
GTPase?
Mutations?
A
repairs damage
Mfn and OPA1
autosomal dominant optic atrophy, CMT 2A, ROS
2
Q
Fission in mitochondira
GTPase?
Mutations?
A
required for mitophagy
Fis1 and Drp
ROS
3
Q
TOM/GIP
A
translocase of outer membrane
passive, facilitated diffusion
4
Q
TIM
A
translocase of inner membrane
gated channel with active transport
protein enters by N’, unwound
Hsp70 rewinds
5
Q
1e- = ____ H+
____ H+ = 1 ATP
A
1e- = 5 H+
3 H+ = 1 ATP
6
Q
ATP synthase F1
A
bound to F0
enzyme that makes ATP
7
Q
ATP synthase F0
A
spans inner membrane, H+ channel
8
Q
____ is final electron acceptor in ETC and makes _____
A
O2, H20
problems lead to ROS
9
Q
Mitochondrial regulation of cell death
A
Bak/Bax make outer membrane permeable
Cytochrome C leaks into cytoplasm
Binds complex and forms apoptosome
Activates caspases
10
Q
Ischemic injury leading to necrotic cell death
A
MPTP makes inner/outer membrane permeable
Cytochrome C release and disruption of H+ gradient
No ATP production (ATPsynth = ATPase)
11
Q
Mitochondrial dysfunction consequences
A
Can't produce ATP Produces ROS (oxidize proteins, lipids, DNA)
12
Q
Quality control
A
Mitochondrial proteases:
mAAA (mutation = hereditary spastic paraplegia)
iAAA
Lon
Fusion/fisson (redistribute or mitophagy)
Apoptosis
13
Q
Arsenic toxin mechanism
A
inhibits oxidative phosphorylation and ATP production
14
Q
Epithelial to mesenchymal transition
A
Epithelial loses polarity and cell adhesions
Migrates and becomes invasive
15
Q
Functions of epithelial tissues
A
protection selective transport/absorption/secretion biochemical modification and processing sensory reception transduction communication
16
Q
Apical and basal polarity
A
Differences in:
transporters, ion channels, exo/endocytosis receptors, cell-cell, cell-lamina
Cytoplasm is also polarized
17
Q
Cell junctions: tight junctions
A
highly selective
limit/control diffusion between cells
Core proteins: occludins, claudins
18
Q
Cell junctions: adherence junctions
A
promote attachment, polarity, organization
decide stem cell behavior
Core protein: cadherins (actin to cyto)
19
Q
Cell junctions: desmosomes
A
mechanical strength
resist shearing forces
Core protein: cadherins (intermediate filament to cyto)
20
Q
Cell junctions: gap junctions
A
rapid communication between cells
joint cytoplasm
21
Q
Apical modifications to epithelial cells
A
microvilli (actin bundles, increase surface area)
ex: stereocilia sensory cells (ear)
cilia
primary cilium (controls proliferation, fate, and function)
motile cilia
sensory cilia
22
Q
Basolateral modifications to epithelial cells
A
infolds/outfolds to increase surface area
unorganized
seen in transport dependent cells
23
Q
Components of basal lamina
A
collagen (type IV, network)
glycoproteins
laminins
entactin
24
Q
Functions of basal lamina
A
- attach epithelia to underlying CT (via hemidesmosomes and focal adhesions, both using integrins)
- filtrations to/from epithelia
- establish/maintain polarity
- highways for cell migration through CT
- barrier to microbes/cancer
- control gene expression to affect proliferation
- scaffolding function - repair
25
2 ways cells can secrete
exocytosis
| total cell disintegration
26
Exocrine glands
small consistent output (can be upregulated)
unidirectional secretion onto apical side
have secretory units: alveoli, acinar, tubular
have ducts: simple/compound
27
Endocrine glands
Hormonal control
no ducts, secrete to blood
surrounded by basal lamina and CT
secreted through basal lamina
28
Types of exocrine glands
1. mucous (viscous, glycoprotein)
2. serous (watery, salts)
3. mixed
29
4 characteristics of stem cells
1. competent for cell divsion
2. self re-new (create mother)
3. produce differentiated cells types specific to epithelia
4. divide very slowly (lots of regulation)
30
Transit amplifying cells
daughter cells of stem cells that proliferate faster
31
Principles of stem cell pathways
Each path used by distinct cell lines/organs
| Single path triggers different effects in different cell lines
32
Some examples of stem cell pathways/signal systems
1. Wnt
2. Shh
3. TGF-ß
4. Notch
5. RTK (ex. EGFR, tx: Tarceva [erlotinib] anti=tumor
6. FGF
33
Carcinoma
cancer with epithelial origin
34
Adenocarcinoma
cancer with glandular epithelial origin
35
Therapeutic targets for cancer
Signal systems that control development
Internal cell cycle control factors
Factors that control DNA repair
Factors that control apoptosis
36
Cystic fibrosis pattern of inheritance
| mutation
Autosomal recessive
| Chr 7 - CFTR gene, F508del
37
Cystic fibrosis pathophysiology
Problems in salt and water movement
| Thick secretions
38
Cystic fibrosis clinical signs
```
Sinus: chronic infections, nasal polyps
Lung: recurrent infections, bronchiectasis
Pancreas: exocrine pancreatic insufficiency (85%)
greasy, bulky stool
malabsorption, CF diabetes
meconium ileus
no vas deferens
clubbing
increased sweat chloride
```
39
Cystic fibrosis screening
newborn screen - asymptomatic or meconium ileus (15%)
| older children - failure to thrive, abnormal stool
40
Cystic fibrosis treatment
nutrition
lung disease treatments (airway clearance, antibiotics, anti-inflammatory
CFTR modulators
41
CFTR modulators
```
Ivacaftor (Kalydeco): class III, potentiator
Lumacaftor/ivacaftor (Orkambi): class II, corrector and potentiator
```
42
Components of cilia
Basal bodies
Axoneme
Transition zone
Ciliary membrane
43
Intraflagellar transport
bidirectional
Anterograde: kinesin-2, IFT-B complex
Retrograde: dynein-2, IFT-A complex
44
Ciliary formation/assembly
Basal body formation from older centriole (G1/S)
| Ciliogenesis (subsequent G1/G0)
45
Motile cilia
movement
dynein dependent sliding motion
9+2 (can be 9+0)
46
Sensory cilia
9+0
| lack dynein arms
47
Pathways that function through cilia
SHh (glioma tumor)
Wnt
PDGF
FGF
48
Advantage of cilia in signaling pathway
```
cell antennae
concentrates signals
high receptor surface to volume ratio
positioned away from interfering cellular domains
mechanical detector of flow
```
49
Cilia homeostasis function
Hh targets: limb, bone, nerve formation/homeo
Ciliary signaling: left/right asymmetry of body
9+0 motile leftward flow
50
Examples of ciliopathies
Bardet-Biedl Syndrome (AR, vesice transport)
| Polycystic Kidney Disease (AD and AR forms)
51
Core cells of CT
```
mesenchymal cells
fibroblasts
osteoprogenitor
chondrocytes
adipocyte
myofibroblast (smooth muscle)
```
52
Immigrant cells of CT
```
lymphocytes
macrophages
neutrophils/eosinophils
mast cells
osteoclasts
```
53
Functions of macrophages
phagocytosis of cells and ECM
promote/control angiogenesis
send signals to other cells
54
Types of collagen
Fibrillar (rope, head to tail, bone/tendon)
Fibril-associated (link collagen to collagen or other)
Network (thin sheets, basal lamina)
55
Dense vs. loose CT
Dense: irregular or organized parallel (lig/ten)
high in ground substrate and low in cell density
Loose: thin irregular, (capillaries and nerves)
high in ground substrate and cell density
56
Intracellular (first step) collagen synthesis
1. polypeptides on ER
2. translocated to ER lumen
3. post-trans mods
4. assembled to triple helix
57
Extracellular (second step) collagen synthesis
1. protease cleavage (N-telo peptide signal)
2. formation of bundles/end to end polymers
3. enzyme catalyzed crosslinks
58
Ehlers-Danos syndrome
collagen disease
59
Elastic fibers in ECM
```
Elastin
Fibrillin (mutation = Marfans)
```
60
Ground substrate in ECM
Proteoglycans
Other proteins (enzymes, GFs, proteases)
Inorganic solutes
Water
61
ECM injury repair steps
Inflammation
New tissue formation
Tissue remodeling
62
ECM injury - inflammation
```
Fibroblasts/mast/macro increase H2O perm
Monocyte/lymphocyte migration
WBC to wound
Proliferation/differentiation monocytes to macro
Histamine
Cytokines (chemoattractant for WBC)
```
63
ECM injury - new tissue formation
Fibroblasts divide/secrete ECM
Cytokines (regulate proliferation of fibroblasts) and GF's
Macrophages: angiogenesis, repair, remodel
64
ECM injury - tissue remodeling
CT extends
Cellularity is reduced
Scar formation (disorganized CT)
65
Inflammatory disease in ECM
```
Crohn's/UC
Rheumatoid arthritis
stomach ulcers
skin disorders
chronic inflammation = GI/colon cancer (promote angiogenesis)
```
66
Function of cartilage
resilient/pliable support
| directs formation of bone
67
Types of cartilage growth
```
appositional growth (from surface)
interstitial growth (within lacunae)
```
68
3 types of cartilage
hyaline cartilage
elastic cartilage
fibrocartilage
69
Hyaline cartilage
thin, irregular 3D
ground substrate has lots of proteoglycans
hyalurnoic acid (promotes hydration)
avascular (diffusion of metabolites)
70
Elastic cartilage
interconnecting elastic sheets (lamellae)
| ex: external ear, epiglottis, larynx
71
Fibrocartilage
regularly arranged cartilage
| extension of dense CT
72
2 types of bone formation
```
Intramembranous ossification (CT to bone, flat bones)
Endochrondral ossification
```
73
Osteoblasts
secrete bone matrix (osteoid)
| secrete matrix vesicles (Ca2+, PO43-)
74
Osteocytes
Withdraw from cell cycle (G0)
Some matrix modifying
Long processes to surface for signals
Gap junctions b/t cells with processes
75
Osteoclasts
```
Hematopoiesis born (monocyte)
multinucleated
degrade bone/cartilage matrix
angiogenesis
CT migration
innervation
Ca2+ mobilization
```
76
Fibrodysplasia ossificans progressive (FOP)
BMP-4 gene translocated to lymphocyte promoter in Bcell
BMP presence in ECM (with immune cells)
Acts on mesenchymal stem cells/fibroblasts
77
Bone remodeling
```
short range signals (shh, Notch, TGF-ß [BMPs])
long range signals (parathyroid hormone (up), calcitonin (down)
mechanical stress
neuronal stimulation (CNS stimulation)
```
78
Smooth muscle contraction differences
1. Ca2+ binds calmodulin
2. Complex binds CaMkinase
3. CaMkinase phosphylorates myosin light chain
No troponin, still Ca2+
Slower
Ca2+ pumps/Na+-Ca2+ in sarcolemma
79
Contractile and linker proteins in skeletal muscle
Dystrophin (actin to PM, not myofibril actin)
Titin (myosin to Z line, organizes thick filaments)
Nebulin (organizes thin filaments)
A-actinin (crosslinks actin at Z line)
80
______ are wrapped into _______, wrapped by their own ______
myofilaments, myofibrils, SR
81
T-tubule to SR biding triad
DHPR: in t-tubule membrane
Voltage gated Ca2+ channel
mutation: muscular dysgenesis
RyR: in SR membrane
82
EC coupling differences in cardiac/smooth
Cardiac: Ca2+ entry causes depolarization
Smooth: no t-tubule/SR due to thin fibers
83
Skeletal muscle fatigue
Decrease in both force and speed
Increased Pi, decreased pH
Affected steps:
1. AP propagation in t-tubule (K+ buildup, Na+ reduced)
2. Ca2+ release from SR (Pi buildup)
3. Ca2+ effect on troponin (H+ competition)
4. Force generation by myofilaments
84
Satellite cells
```
located on surface of fibers
differentiate into new fibers
Responsive to:
Growth factors, Nf-kB, NO, myostatin (TGF-ß)
Exercise (extra nuclei)
```
85
Grading tension in skeletal muscle
increase frequency of AP
recruit additional motor units
length change (minimal, usually optimal)
86
Grading tension in cardiac/smooth muscle
neurotransmitters/hormone regulation
| cell length influences (since no bony attachments)
87
Hypertrophic cardiomyopathy
AD, genetic heterogeneity, incomplete penetrance
88
Hypertrophic cardiomyopathy clinical presentation
```
cardiac murmur (if LV outflow obstruction)
pump fail (dyspnea, angina)
arrhythmia (syncope, sudden death)
```
89
Hypertrophic cardiomyopathy molecular defects
```
missense mutation in structural gene
cardiac hypertrophy (organ hypertrophy)
myocyte disarray (function compromised)
interstitial fibrosis (arrhythmia)
dysplastic intramyocardial arterioles (ischemia)
```
90
Hypertrophic cardiomyopathy treatment
echo, EKG, MRI, family hx, genetic testing, chest xray
91
Malignant hyperthermia
AD and environmental
92
Malignant hyperthermia clinical presentation
```
muscle rigidity (masseter spasm)
acidosis (increased CO2)
Rhabdomyolysis
Hyperthermia
Tachycardia, tachypnea, hyperkalemia
```
93
Malignant hyperthermia molecular defects
RYR1 mutation (~70%)
Increased Ca2+ release
Increased O2 consumption and anerobic metabolism
94
Malignant hyperthermia treatment
```
Dantrolene (RyR1 antagonist)
Hypervent with O2
Bicarb
Cool patient
Treat arrhythmias (w/out Ca2+ blockers)
```
95
DMD
X-linked, males only
96
DMD clinical signs
```
early onset (3-5 yrs)
abnormal gait (toe walking)
Gowers' sign
Calf pseudohypertrophy
High CK (1000s)
Cardiomyopathy
```
97
DMD molecular defects
Dystrophin mutation
| big deletions, framshift
98
DMD treatment
corticosteroid (prolong ambulation, side effects)
