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M2M Unit 4 > Exam 4 > Flashcards

Exam 4 Flashcards

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1
Q

Outer membrane vs. inner membrane of Mitochondria

A

Outer: very porous; folded proteins can pass through channels; General Import Pores
Inner: very tight; site of oxidative phosphorylation where generation of proton gradient exists; Tim23 and Tim22

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2
Q

General Import Pores

A

transports folded proteins
N terminal of protein has positive leader sequences that binds to negative inside of channel
Facilitated diffusion and ATP independent!

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3
Q

Tim23 and Tim22

A

found on inner mitochondrial membrane
very tight channel to protect proton gradient
Gated channels
Positive N terminus binds to outside and protein gets transported inside.
Protein is unfolded and plugs whole to prevent loss of proton gradient.
Hsp70 binds to unfolded protein and uses ATP hydrolysis to make a kink and pull protein in the channel

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4
Q

Fission - mito

A

Drp1 and Bax facilitate the pinching off and division of mitochondria

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5
Q

Fusion

A

Mfn and OPA mediate fusion of mitochondria

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6
Q

how many calories are made with each ATP to ADP conversion?

A

7.3 kcal/mol

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7
Q

NADH structure

A

Two pentose rings hooked by two phosphates

an adenosine head

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8
Q

Oxidized form of NADH

A

NAD

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9
Q

Reduced form of NADH

A

NADH

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10
Q

Oxidative phosphorylation

A

Glucose is broken into two pyruvates (3C) that occurs in lack of oxygen to make 2 ATP
Pyruvate moves to mito and diffuses across outer membrane where it goes into the TCA cycle to break down into CO2, 3 NADH, and 1 FADH.

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11
Q

Electron Transport Chain

A

NADH donates electron and gets oxidized to pump protons outside.
one NADH transfers 5 protons out and forms 1 water

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12
Q

ATP Synthase

A

driven by proton gradient
protons run through channel and phosphorylate ADP to ATP.
single glucose gives 22 ATP

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13
Q

ATP synthase conformations

A

ADP and pi
brings ADP and Pi together
Looses affinity to ATP

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14
Q

How is apoptosis induced in mito

A

by activation of cytochrome c

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15
Q

Cytochrome c

A

usually involved in oxidative phosphorylation (complex IV)

CytoC binds to form an apoptosome that signals to activate caspases.

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16
Q

How is apoptosomes regulated?

A

reducing or oxidizing cytochrome C by NADH
all healthy cells form apoptosomes, but cell changes mind if the cell has the energy to reverse the activation of cyto c.
if the cell is lacking energy, cyto C cannot be inactivated and drives to apoptosis.

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17
Q

Quality Control in Mitochondria

A

Molecular: set of proteins that detect oxidative phosphorylation enzymes that are defective and degrades them
Mitophagy: degrade the piece of mito that is defective
Apoptosis: kills the cell all together

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18
Q

Molecular quality control in Mito:

A

mAAA are proteins that detect mutations in Oxidative phsophorylation enzymes and degrades them.
Lots of mutations associated with these: hereditary spastic paraplegia.

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19
Q

Primary Cilia

A

Microtubule extension out of PM on apical surface
senses physical and biochemical environment
a 9+0 arrangement
signaling and NOT motile

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20
Q

Motile Cilia

A

used when movement of fluid is required
respiratory, neural, and reproductive
2 extra MT in center of axonomes

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21
Q

central pair

A

the extra two MT in axonemes that give the motile cilia a characteristic 9+2 arrangement

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22
Q

Components of cilia

A 
Basal Body anchor
Transition Zone
Axeneme scaffolding
Intraflagellar transport
Outer Ciliary Membrane
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23
Q

Basal Body

A

anchor to the axoneme structure - incredibly stable
derived from centrosome
200nm by 500 nm
central hub with radiating modified microtubules in TRIPLET
9 subunits; 3 MT per subunit

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24
Q

Axoneme

A

scaffold structure in cilia

DOUBLET MT with central pair of MTs which makes the m more stable than singlets.

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25
Q

Nexin

A

the linker between doubles in cilia to ensure integrity

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26
Q

How to cilia move?

A

dynein arms grab onto neighboring subunits and cause a pulling force that leads to motility

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27
Q

Intraflagellar transport

A

Active mechanism that regulates which components can enter and move down the cilia through the transition zone.
Bidirectional trafficking mechanism in cilia
Proteins/vesicles must have a localization signal very similar to control of nuclear pore.

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28
Q

Transition Zone

A

the linkage domain or gatekeeper of cilia
links basal body to axoneme
ensures that proteins and membranes components of cilia are distinct from PM
contains Alar Sheets
mutated in ciliopathies

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29
Q

what is analogous to nuclear pore in cilia

A

alar sheets in the transition zone

limit cytoplasmic and diffusible proteins from entering

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30
Q

what stage does ciliogenesis occur

A

G0 or G1

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31
Q

First step in ciliogenesis

A

basal bodies from centrioles migrate to surface of cell and attach to rich cortex.
along the way they associate and fuse with ciliary membrane vesicles that fuse with plasma membrane

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32
Q

elongation of cilia

A

once at Plasma membrane, basal body nucleates outcroth of axoneme

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33
Q

what forms the transition zone of the cilia

A

distal regions of the basal body

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34
Q

maintenance of cilia

A

proteins synthezied in cyto are transported via IFT

tubulin continues to be incorportated at the tip, but cilia does not elongate further.

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35
Q

What drives movement to the + end in cilia?

A

Kinesin 2 and IFT-B

This is the end of the cilia

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36
Q

what drives movement to the - end of cilia?

A

Dynein-2 and IFT-A

returns to the base of the cilia

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37
Q

Basal body formations

A

derived from centrioles and are typically formed during cell replication.
Mother centrioles are associated with ciliogenesis
New centrioles always develop at the base of the mother centriole.

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38
Q

How are multi-ciliated cells made?

A

Must be differentiated cell
Bypass the once and only once duplication of DNA and centrioles, to make multiple centrioles.
Forms dueterosome and all migrate to build cilium structure

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39
Q

deuterosome

A

used in multi-ciliary cells and help recruit machinery to build cilia

1) daughter centriole supports procentriole nucleation via deuterosome formation.
2) deuterosomes are released into cytoplasm
3) centriole growth from deutersosome
4) centriole release and maturation for docking cilia growth

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40
Q

Physical benefits of Cilia

A 
Concentration of signal
localized
polarized
fluid mechanics
charge disruption
flow sensing
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41
Q

concentration of signal - cilia

A

cilia create microenvironment for signaling with high surface receptor to volume ratio

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42
Q

How are cilia flow sensing

A

mechanical bending senses fluid flows

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43
Q

Receptors in Cilia detect

A

physical stimuli, light, chemical stimuli ( hormones, chemokines, GFs, morphogens)

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44
Q

Result of ciliary signaling

A

cell proliferation, motility, polarity, growth, differentiation, tissue maintenance

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45
Q

Sonic Hedgehog pathway - unstimulated

A

PTCH1 is on surface of cilia and Gli is respressed by SUFU

SMO is sequestered to intracellular vesicle

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46
Q

Sonic Hedgehog pathway - stimulated

A

Hh binds and causes PTCH1 to no longer be on surface cilia membrane and for SMO to translocate to cilia surface
This causes Cli to be transported to tip of cilia and represses SUFU to cause activation of GliA.
GliA is transported by dynein into cytoplasm and nucleus to become TF.

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47
Q

Hh Signaling effects..

A

Limb formation - growth, digit number, polarity
Bone formation: cell proliferation, diff, growth
Neurogenesis: neural tube formation, differentiation, cell migration

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48
Q

Left right axis formation and cilia

A

gastrulation establishes anterior and posterior
Ciliary pits beat in a rotary fashion at 600 bpm at the proper angle to generate net leftward flow. This causes asymmetry of growth factors and biochemical signals.
Depends on the primary cilia to sense the mechanical flow.

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49
Q

Characteristics of Ciliopathies

A

1) Rare
2) pleiotropic
3) most affect structural elements of cilia
4) Diverse range of mutations - most occurring in transition zone
5) genetically complex
6) phenotypes overlap

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50
Q

Bardet-Biedl Syndrome

A

Mutation in gene that encodes basal body proteins in cilia
affects vesicular trafficking, MT anchor, and IFT
AR disorder
pathology: photoreceptor degradation, mental retardation, kidney defects, asomnia, obesity, diabetes

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51
Q

Polycystic Kidney Disease

A

AD and AR both exist
1:1000 (maybe more)
mutation in polycystin1 and 2
pathology: renal cysts, renal failure and liver and pancreatic cysts, intracranial aneuryisms

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52
Q

Polycystin 1 and 2

A

mutated in PKD
channel proteins located at cilia base, just above transition zone.
sense mechanical urine flow to signal for Ca release to induce proliferation and cystogenesis

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53
Q

Function of epithelial

A

barrier, absorption and transport, secretion, movement though passageways, biochemical modification, sensory reception, communication

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54
Q

endothelium

A

epithelial cells that line the blood and lymph vessels

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55
Q

mesothelium

A

epithelial that encloses internal spaces of the body cavity

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56
Q

Vasculature in epithelium

A

avascular
no direct blood supply, nutrient and oxygen
diffuse through CT, BL to reach epithelial cells

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57
Q

Formation of epithelium

A

begins with primitive epithelium, which is just a single sheet of cells.
derived from endo, meso, and extoderms
these cells receive morphogenetic signals for transformation that causes disassembly and reformation during various parts of development in uterus.
some detach and migrate to become mesenchymal
this process stops at birth but is hyper-activated in cancer

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58
Q

Mucosae

A

epithelia in most internal linings
has outer epithelium
lamina propria: CT directly under eptihelia
submucosa: deep CT

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59
Q

Simple vs Stratified epithelia

A

simple: single sheets
stratified: multiple sheets

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60
Q

Squamous vs. cuboidal vs. columna

A

squamous: outer layer is flat (long but short)
cuboidal: cube shaped
columnar: tall cells

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61
Q

Pseudo-stratified Epithelia

A

all cells remain in contact with BL, but not all reach free surface

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62
Q

Transitional epithelia

A

stratified, but histologically look like a single layer

found in bladder

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63
Q

Function of epithelial polarity

A

unidirectional secretion or absorption

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64
Q

transcytosis

A

transport of vesicles in epithelia that is unidirectional - movement though the cell

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65
Q

Apical surface specializations

A

Microvilli and Cilia

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66
Q

Microvilli

A

located on apical surface.
extension of actin that increase surface area.
Stereocilia is most common: found in epididymis and in ear.

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67
Q

Basolateral specializations

A

lack structural organization

still has folds to increase surface area

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68
Q

Tight Junctions

A

Zonula Occludens
uses claudins and occludins
appear like a belt surrounding cells
Limit paracellular transport and promote Transcellular transport.
work intracellularly to regulate cyto proteins that monitor gates

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69
Q

Adhearence Junctions

A

Zona Adherens
Cadherins that connect to actin skeletal
cadherins recruit kinases and phosphatases to regulate gene expression control cell division and polarity

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70
Q

Desmosomes

A

also use cahderins, but bind to Intermediate filaments
Promote structural integrity of epithelium
mutations cause blistering

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71
Q

Gap Junctions

A

actual channels that promote rapid communication between the cells through channels.
allow flow of ions, second messengers.
Non-specific!

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72
Q

Basal Lamina Components

A

collagen, glycoproteins, laminins, entactin

high variable depending on cell type.

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73
Q

Function of Basal lamina

A

epithelial attachment, selective filtration, polarity, highways for migration, barrier to invading materials, control gene expression, tissue scaffolding

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74
Q

Attachments to basal lamina

A

Hemidesmosomes and Focal Adhesions

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75
Q

Hemidesmosomes

A

link internally with integrins to intermediate filaments and provide structural connection.

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76
Q

Focal Adhesions

A

use integrin to attach to actin cytoskeleton.

have signaling capabilities to provide role in polarity

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77
Q

Exocrine Glands

A

secretes from apical surfaces of epithelia
multicellular
begin as sheet of epithelia that invaginates and elongates but remains connected as it grows.
Contains Acini that flow into the ducts

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78
Q

Acini

A

secretory units in exocrine glans that are located at the base and secrete into the ducts.

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79
Q

Endocrine glands

A

secrete hormones into bloodstream from BL side
start with primitive epithelium that invaginates, but there is a detachment from the apical surface.
Hormones must travel through BL of gland and then through another BL of the vessel to get into bloodstream

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80
Q

Transit Amplifying cells

A

intermediates in the process of differentiation of epithelial cells.
these cells have a shortened lifespan to divide rapidly and then differentiate.
much faster than stem cells.

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81
Q

WNT pathway in colon

A

WNTs are secreted ligands that bind to receptors to regulate downstream protein that regulates beta-catenin to stimulate cell division and inhibits differentiation.

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82
Q

APC

A

ACP inhibits B-catenin by sequestering it in the nuclues

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83
Q

WNT 7A

A

when gene expression of WNT7a is increased, associated with loss of function of APC in colon cancer, but not lung!
Decreased WNT-7s is not associated with colon cancer, but it is associated with Lung cancer.

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84
Q

WNT7A in lung

A

WNT7A acts on beta catenin to inhibit cell division and promote differentiation.

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85
Q

Cadherin and squema cell carcinoma

A

1) mutations in cadherin disrupt junctions in eptihelial to make more migratory
2) change in signaling pathways to change gene expression
3) it could be that low Cadherin is the effect of squema carcinoma and not the cause…

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86
Q

what binds to the antigen

A

the variable region

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87
Q

what gins to the antibody

A

the epitope

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88
Q

Superficial Fascia

A

CT near body surface with lots of fat; easily dissected

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89
Q

Deep Fascia

A

tougher deeper region of CT

Prominent thick epimysium (outer covering of muscles) and ligaments, tendons, joint capsules.

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90
Q

Connective Tissue Function

A

Mechanical strength, regulation of nutrient and metabolism between organs and blood vessels, control behavior and function of cells contacting ECM

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91
Q

Types of CT

A

Resident and Immigrant

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92
Q

Resident CT

A

produce and secrete ECM and proliferate to produce new CT

mesenchymal, fibroblasts, myofibroblasts, Adipocytes, osteoblasts, osteocytes, chondorcytes, smooth muscle

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93
Q

Mesenchymal cells

A

Resident CT
the precursors to all CT found primarily in embryogenesis
high telomerase activity
give rise to fibroblasts

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94
Q

Fibroblasts

A

Resident CT
pre-eminent cells in most CT
synthesizes fibrous proteins, proteogycans, and ECM components
capable of cell division
Sensory and proliferation is highly regulated - scarring is hypertrophy of fibroblasts
many different types of fibroblasts depending on cell type.
Can transform into variety of CT (adipocytes, Smooth muscle, chondrocytes, osteoprogenitors) - though this has not been proven in live human cells.

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95
Q

Myofibroblasts

A

Resident CT
derived from fibroblasts, capable of smooth muscle like function
Found at wound sites to contribute to retraction and shinkage of scar tissue.

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96
Q

Adipoctyes

A

Resident CT
fibroblasts derivatives or primitive mesenchymal
store fat and energy
Brown Fat: found in newborns with many mito to convert FA into heat.

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97
Q

Chondrocytes

A

Resident CT

cells that make cartilage

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98
Q

Immigrant blood derived CT

A

originate from precursors circulating in blood;
produced form hematopoietic cells in marrow and migrate into blood and CT
acct as part of immune system
Lymphocytes, macrophages, neurophils, esosinophils, mast cells, osteoclasts

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99
Q

Lymphocytes

A

immigrant CT

acquired immunity

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100
Q

Macrophages

A

immigrant CT
phagocytose cells, ECM, and non-cellular material
stimulate angiogenesis, remove damage tissue, remodel normal developing tissue

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101
Q

Neurophiles and eosinophils

A

immigrant CT

defense against microoorganisms

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102
Q

Mast Cells

A

immigrant CT

secretory, release vasodilators to promote swelling

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5
Perfectly
103
Q

Osteoclasts

A

immigrant CT
derived from blood monocytes
promote bone resorption and remodeling

104
Q

Structural aspects of ECM

A

Collagen, Elastic fibers

105
Q

Collagen

A

fibrous proteins that form aggreage fibers
triple helix
many different types due to alpha chain

106
Q

Fibrillar collagen

A

large bundles of collagen fibrils
collagen alighned head to tail to generate long strands.
provides tensile strength
(collagen I)

107
Q

Fibril-Associated collagen

A

decorate surface of collagen fibrils
linke collagen fibrils together or to the BL
(Collagen 4)

108
Q

Network Forming Collagen

A

think and assemble into interlaced networks
form porous cheets
Forms basal lamina, anchors BL and cells to ECM, filtration barriers in kidney

109
Q

Loose Connective Tissue

A

thick collagen fibrils that are sparse

irregular lattice network with high cell density and ground substance, blood and lymph, nerves

110
Q

Dense connective tissue

A

thick collagen that are more abundant
irregular or parallel arrangements for greath strength and to resist force.
ligaments and tendons

111
Q

Collagen syntehsis

A

synthesized and modified intracellularly and exported for further modification

112
Q

Intracellular collagen synthesis

A

peptide synthesis in ER lumen, post-trans modification by glycoslyation and hydroxylation, forms triple helix in golgi

113
Q

Extracellular collagen synthssis

A

N and C are cleaved by specific proteases
release of N-telo peptides cause formation of bundles and end to end polymers; crosslinks are formed to increase tensile strength

114
Q

N-Telo peptides

A

fragments created with extracellular processing of collagen.

high levels in blood or urine due to a Connective Tissue disease

115
Q

Elastic Fibers

A

elastin and fibrillin
create resiliency when stretched and relaxation when released
propels blood through capillaries and arteries

116
Q

Elastin

A

filamentous, random coil conformation

fibroblasts secrete monomers and form extracellular filaments and sheets with numerous cross links

117
Q

Fibrilin

A

is interwoven in elastin to help form a fiber

118
Q

Ground substance

A

hydrated gelatinous material that surrounds structural elements
Proteoglycans are most responsible.

119
Q

Proteoglycans

A

protein core with large acidic GAGs
highly negative charge *hydrophilic
binds to both active and inactive proteins

120
Q

Elements of ground substance

A

Proteoglycans, proteases that process collagen and proteins, growth factors and polypeptide ligands, inorganic and small organic solutes

121
Q

General Steps of Wound healing

A

Inflammation and clotting; Proliferation /New tissue formation; Tissue remodeling

122
Q

Inflammation and clotting - wound healing

A

ruptured tissues release platelets into connective tissue and activates them to produce blood clots that temporarily seal wound.
fibroblasts, mast cells, and macrophages release signals to increase water permeability, increase cellular permeabile to monoctyes, lymphocytes, and blood cells, attract migration of white cells, stimulate fibroblasts and differentation of monocytes into macrophages

123
Q

Hitamine

A

released during inflammation and clotting by mast cells to promote endothelial permeabilization
signal to hematopoietic tissue to stimulate WBC production

124
Q

cytokines - wound healing

A

secreted by white blood cell derivatives and by fibroblasts

signal to hematopoietic tissue to stimulate WBC production

125
Q

Proliferation/New Tissue Formation in wound healing

A

fibroblasts divide and secrete ECM components
signals trigger division and differentiation of epithelial; ECM proliferation and remodeling; macrophages trigger angiognesis, repair and remodeling

126
Q

Tissue remodeling in would healing

A

the ECM, cellular composition, and structure of CT, epithelium are altered depending on wound location and severity
cellularity (density of cells) is reduced; ECM is thinner, imperfect remodeling forms scar tissue

127
Q

chronic inflammation is hallmark of which diseases…

A

ulcerative collitis, Crohns, rheumatoid arthritis, stomach ulcers, skin disorders

128
Q

Function of bone and cartilage

A

mechanical support; attachment of muscles and joints, protection of organs, regualtion of calcium homeostasis, housing of homeoploitic tissue

129
Q

Bone characteristics

A

highly dynamic - constant turnover and rebuilding
highly vascularized
maintaisn precursor cells capable of cell division and differentiation into bones.

130
Q

Cartilage characteristics

A

must less dynamic than bones
avascular in matrix
limited ability to repair in adults
converted to bone in adults

131
Q

Cartilage Function

A

resilient but pliable structure
direct formation and growth of bone
retained in teh trachea, nasal passage, ear, intervertebral discs, ribs, skull, and tendons

132
Q

Where is cartilage located in adults?

A

only on articular surfaces

133
Q

Chondrocytes

A

cells that make the cartilage matrix and tissue

differentiated from sheet of primitive mesenchymal stem cells

134
Q

Perichondrium

A

external layer of CT that surrounds cartilage; thin but dense
promotes and maintains growth; gives rise to chondrocytes

135
Q

Chondrocytes during growth…

A

proliferate and secrete componentes of ECM. As they surround themselves they isolate themselves in the Lacuna.

136
Q

Chondroblasts

A

proliferative chondrocytes, (essentially chondrocytes but in cell division.
when growth is completed, they chondrocytes withdraw from cell cycle and retain capability to secrete cartilage matrix, but at lower rates.

137
Q

Hyaline Cartilage

A

collagen with relatively thick fibrils
irregular 3D pattern
rich in proteoglycans and hyaluronic acid (protein free GAG) to promote hydration and flexibility.

138
Q

Hyaline Cartilage ECM

A

metabolites readily diffuse
promotes resiliency to compressive force during joint movement
allows growth of condorcytes and matrix from within matrix
calcifies during growth

139
Q

Elastic Cartilage

A

thick collagen fibrils and proteoglycans
abundance of elastic fibers and intrconnecting sheets of elastic material
found in external ear, epiglottis, larynx
matrix does not calcify

140
Q

Fibrocartilage

A

bundles of regularly arranged collagen that is similar to dense CT
hybrid between dense CT and cartilage
resists compression and shear force
where tendons attach to bone and in intervertebral discs

141
Q

Types of cartilage matrix

A

hyaline, elastic, fibrocartilage

142
Q

Formation of cartilage

A

mesenchymal cells divide and differentiate into chondrocytes.
Chondrocytes secrete matrix and individual chondorcytes become encase in a lacuna.

143
Q

How does cartilage growh?

A

apposition and interstital

144
Q

appositional growth of cartilage

A

growth on surface
perichondrium, mesenchymal and fibroblasts proliferate and differentiate into chondrocytes to secrete matrix.
upward thickening

145
Q

Interstitial growth of cartilage

A

growth form within
chondrocytes within matrix proliferate within lacunae and secrete ECM.
cellular division in lacuna.

146
Q

Periosteum

A

compact bone made out of fibroblasts

outer region of the bone

147
Q

Spongy bone

A

also called cancellous and trabecular.

inner portion of bone with thick anastomosing spicules called trabeculae.

148
Q

purpose of trabeculae

A

surface area for metabolism; hold bone marrow

149
Q

White bone marrow

A

adipose cells

150
Q

Endosteum

A

spongy bone that stores and mobilizes calcium

151
Q

Osteoprogenitor

A

mesenchymal stems calls whose daughters become osteoblasts and osteocytes
present in both perosteal and endosteal surfaces

152
Q

Osteoblasts

A

line inner lining of both periosteal and endosteal surfaces where bone growth and remodeling occurs.
secrete osteoid
pinch of matrix vesicles
capable of cell division

153
Q

Matrix vesicles

A

contains enzymes that initiate bone calcification

154
Q

Osteocytes

A

derivatives of osteoblasts; form as they become surrounded and encased by bone matrix.
arrested in G0
use canaliculi for communication
don’t secrete matrix, but modify and sense matrix to send signals for regualtion

155
Q

canaliculi

A

long tiny channels that allows for communication of osteocytes with surrounding matrix

156
Q

Osteoclasts

A

derived from monocytes in blood or hematopoietic stem cells.
Resemble macrophages: perform phagocytosis and angiognesis
degrade bone to allow inward growth of blood vessels and nerves
Resorb bone for purpose of mobilizing Ca into blood stream.

157
Q

Bone Matrix

A

ECM of bone is calcified and pack with collagen
contains negative proteoglycans
contains large amounts of crystallized Ca and PO4 called hydrozyapatite to make mineralized matrix

158
Q

Haversian Canals

A

long bones that traverse the long axis through compact bone

159
Q

Volkmann’s Canal

A

link haversian canals to each other and to the perisoteum at bone surface

160
Q

intramembranous ossification

A

used for flat bone formation
done in absence of pre-made cartilage.
condensation of mesenchymal in loose connective tissue to form osteoprogenitors and eventually osteoblasts.
Osteoblasts secrete osteoid
relatively delay/slow bone formation process

161
Q

osteoid

A

secreted by osteoblstasts

unmineralized ECM of bone

162
Q

Cartilage bone model

A

for long bones
cartilage condenses in CT and forms long bone structure.
Endochondral ossification occurs within bone formation
bone grows intersitially and appositionally
1) pericondrum is converted to perisoteum
2)mesenchymal cells swithc from chondrocytes to bone lineage
3) osteoblasts secrete matrix into cartilage cuasing them to recruit osteoclasts and degrade calcified cartialge and bring with then N and blood vessels.
4) in internal spaces osteoblasts secrete bone matrix

163
Q

Site of ossification of long bones

A

diaphysis and grows outward to epiphysis

164
Q

how does a bone grow in length

A

at the epiphyseal plate
requires cartilage cells
occurs alongside interstitial growth at growth plate

165
Q

Osteoblast vs osteoblast and calcium

A

Osteoclast mobilize calcium; osteoblast: deposit calcium

166
Q

what pathways control bone formation

A

short range signals, long range signals, mechanical stress, neuronal stimulation

167
Q

Short rage bone signals

A

same pathways as epithelial development

Sonic Hedgehog, notch TBGB

168
Q

Fibrodisplaysia Ossificans Provecevia

A

is a disorder in which muscle tissue and connective tissue such as tendons and ligaments are gradually replaced by bone (ossified), forming bone outside the skeleton (extra-skeletal or heterotopic bone) that constrains movement

169
Q

Fibrodisplaysai ossificans provecevia mechanism

A

genetic translocation of BMP4 is linked to lymphocyte promoter.
When this is hyperactive, it inapproprately produces signal that acts on mesenchymal cells and fibroblasts to convert osteoblast progenitors into osteoblasts

170
Q

Long range bone signals

A

parathyroid hormone stimulates Ca release and bone resorption
Calcitonin: decreases Ca release and stimulate bone deposition

171
Q

General Vasculature structure

A

Tunica Intima, Tunica media, tunica adventitia

172
Q

Tunica Intima:

A

innermost layer of vessel; endothelial cells contacting blood
layers of elastic and loose collagenous tissues
always sqaumous to allow for effective diffusion of O2 and CO2.
not most effective transport for glucose and AA

173
Q

Tunica Media

A

middle of vessles

composed of multiple layers of elastic lamina and smooth muscle and collagen

174
Q

Tunica Adventitia

A

outer supporting layer, collagenous tissues

contains vasa vasorum and nervi vascularis

175
Q

How is artery thickness related?

A

thick wall is determined by medial layer.

thickness decreases from heart to arterioles.

176
Q

Large Artery/Aorta Structure

A

Intima: inner layer of endothelial cells and some connective tissue
Media: inner elastic lamina; multiple layers of smooth muscle, outer layer of elastic lamina
adventitia: elastic and strong CT.

177
Q

what is the inner elastic lamina made of?

A

collagen and elastin rich fibers

178
Q

Small muscular arterioles

A

contain intima, media, and adventitia.

Loose outer lamina, but remain inner.

179
Q

Venules vs Arterioles

A

venules lack layers of smooth muscles because they dont’ control blood flow as much..

180
Q

Arterioles vs. Lymphatics

A

mostly of squamous layer, but not much smooth mucles

181
Q

Athlerosclerosis

A

builds up and elaboration of intima that makes lumen smaller

182
Q

Arterial venous shunts

A

control blood flow into capillary bed
contraction: prevents blood flow into capillary, but relaxation promotes flow into capillary.
larger than metarterioles

183
Q

metarterioles

A

control blood flow into capillaries using pre-capillary sphincter that lead directly into capillary bed.

184
Q

Capillary stucture

A

single endothelail cell lining; basal lamina surrounding.

Pericyte wraps partically around it within CT

185
Q

Pericyte

A

cell that is wrapped partially around the capillaries.

involved in repair and angiogenesis upon damage

186
Q

How does fluid get into capillaries?

A

pincytotic vesicles
Fenostrated endothelial cells
discontinous endothelium

187
Q

Pinocytotic vesicles

A

small amount of fluid that is transported across cytoplasm in small vesicles.

188
Q

Fenostrated endothelial cell

A

holes in endothelial cells that permit bulk flow of fluid
present in kidney and liver
filtration still occurs via basal lamina

189
Q

Discontinuous Endothelium

A

allow red blood cells and leykocytes to pass

seen in spleen and is important in immune responses and taking red blood cells out of blood.

190
Q

How does histamine influence permeability of vessles?

A

between endothelial cells.

191
Q

diapedesis

A

process by which leukocytes leave blood by working their way through epithelial wall between cells.
Leukocytes in bone marrow get into blood within 8-10 hours

192
Q

Adeventitia

A

can have vasa visorum as you increase in vein size

193
Q

Varicose veins are due to..

A

valve failure

194
Q

Skeletal muscle characteristics

A

Large 50-100 um diameter, multi-nucleated in periphery, striated, No gap junctions

195
Q

Cardiac Muscle

A

smaller than skeletal, striated, large in diameter but short fibers, Interacalated discs, nucleus located centrally

196
Q

Intercalated discs

A

borders cardiac myocyte..
Adheres cells together in transverse region
gap junctions promote electrical signal propagation in lateral regions

197
Q

Smooth Muscle Characteristics

A

Single nucleus, thin diameter of 2-5 um, spindle shaped with nucleus near center, contain different actin and myosin organization

198
Q

Muscle Fascicle

A

In anatomy, a muscle fascicle is a bundle of skeletal muscle fibrils surrounded by perimysium, a type of connective tissue.

199
Q

myofibril

A

A myofibril (also known as a muscle fibril) is a basic rod-like unit of a muscle cell

200
Q

Endomysium

A

separates muscle fibers
structural role; but also contains specialized laminins to repair neuromuscular junction
signaling molecules

201
Q

Perimysium

A

wraps around the bundles of muscle fibers

contains arteriols and nerve bundles

202
Q

Epimysium

A

covers the muscle; thick connective tissue for protection

203
Q

Embryonic Development of myoblasts

A

myoblast fusion of muscle fibers
fushion to form long cells.
myoblasts are most active during development but exist as satellite cells during adult life

204
Q

Sarcomere

A

repeating units in striated muscle; basic unit of contraction.
Relaxed state is 2.5 um; but continually change length depending on level of contraction.
Bring Z discs together

205
Q

Thin Filament

A

made of actin; specifically F actin
1 um in length
double stranded and helical
bound to two regulatory proteins troposmyosin and troponin

206
Q

Tropomyosin

A

rod shaped regulatory protein that binds to 6-7 actin
covers actin binding site to myosin when relaxed.
When calcium binds to troponin, induces change in tropomysin and exposes actin and mysoin binding sites.

207
Q

Troponin

A

heterotrimer that binds to one end of tropomyosin
Ca sensitive
Ca causes binding to troponin and undergoes conformational change to induce change in tropomysoin and facilitate actin binding to myosin.

208
Q

Thick filaments

A

myosin (1 pair heavy chain and 2 pairs light chains)
situated in a staggered foramtion
1.6 um long and contains 300-400 myosins
Region of ATPase activity

209
Q

When does the power stroke occur?

A

moment actin binds to mysoin.
at resting state, Myosin is locked in spring form.
ATP binds to release myosin from actin.
ATP hydrolysis puts myosin in high energy state.

210
Q

how big is a power stroke?

A

8 nm

211
Q

Different of myosin turn over in fast vs slow twitch muscle

A

Fast: 20 times per second
slow: 5 times per second

212
Q

Cardiac muscle contraction

A

occurs in process similar to skeletal muscle

213
Q

Smooth Muscle Contraction

A

contains no troponin
Calcium binds to calmodulin, which together activate CaMKinase. This phosphorylates light chain of mysoin.
Phosphorylated myosin binds to actin to generate force
relaxation occurs by dephosphorylation.
slower process than in smooth muscle

214
Q

Dystrophin

A

large filamentous protein associated with actin near PM.

links cytoskeleton with ECM

215
Q

Titin

A

maintains highly ordered sarcomeres

links myosin Z disk

216
Q

Nebulin

A

associates with actin and keeps thin filaments organized

passive tension in muscle

217
Q

Alpha-Actinin

A

cross links actin filaments

218
Q

Tropomodulin

A

caps length of actin filament - end

219
Q

CapZ

A

caps to + end of actin

220
Q

Hypertrophic Cardiomyophathy

A

50% of sudden cardiac death
left ventricular thickening
Mutation in myosin heavy chain that binds to actin and ATP
due to missense mutations in many different genes.

221
Q

Phenotype of Hypertrophic cardiomyopathy

A

Cardiomyocyote hypertrophy
Myocyte disarray –> compromises contraction
Fibrosis –> arrhythmia
Displastic intracmyocardial arterioles –> ischemia

222
Q

Symptoms of hypertrophic cardiomyopathy

A

usually asymptomatic

but dyspnea, angina, syncope, cardiac death (enriched in athletes)

223
Q

Clinical Presentation of Hypertrophic cardiomyopathy

A

Carciac murmer, cardiac pump failure (dyspnea, angina) arrhythmia (syncope, sudden death), family screening

224
Q

Rate of diffusion compared to distance

A

rate decreases by distance squared

225
Q

Paravlbumin

A

binds and releases Ca and diffuses father than Ca

mechanism to increase evenness of contraction

226
Q

Myoglobin

A

binds to O2 and stores O2

227
Q

What replenishes ATP during metabolic demand in muscles

A

Creatinine and phosphocreatine

228
Q

Transverse Tubules

A

deep invagination of the sarcolemma, which is the plasma membrane of skeletal muscle and cardiac muscle cells
allows for propagation of signal along length and depth at the same time.

229
Q

Sarcoplasmic Reticulum

A

specialized type of smooth ER that regulates the calcium ion concentration in the cytoplasm of striated muscle cells
puts calcium release within 1 um of all muscle cells.
uniform calcium release

230
Q

Excitation Contraction Coupling in Skeletal Muscle

A

Action potential in motor nerve causes ACh release to activate ACh channel to open and depolarization. Depolarization popogates and occurs in T tubules.
Protein links at T-tubule/SR junction *(triad) are altered to allow Ca release from RyR channels.
Ca binds to troponin and alters Tropomysoin conformation and allows actin to bind.
As long as Ca and ATP are present, contraction continues.

231
Q

When does relaxation occurs in skeletal muscle

A

Ca ATPases pumps Ca back into SR and tropomyosin blocks myosin actin binding site.

232
Q

DHPR

A

Dihyropyridine receptor

voltage gated channel in T tubule

233
Q

RyR

A

Ca release channel in SR

in Skeletal muscle: DHPR conformational change due to depolarization induces a change in RyR to open and release Ca.

234
Q

Malignant Hyperthermia

A

mutation in RyR to cause prolonged Calcium release.
Catastrophic rise in body temperature when exposed to volatile anesthetics because of heat generated to pump Ca back into SR
Dominant disorder
Environmental disorder: okay unless exposed to the anesthetic

235
Q

Volatile Anesthetics in malignant hyperthermia

A

halothane

succinylcholine

236
Q

Phenotype of malignant hyperthermia

A

hypermetabolism, skeletal muscle damage, hyperthermia

237
Q

Specific clinical signs of maligant hyperthermia

A

muscle rigidity (masseter spasm), increased CO2 production, rhabodomyolysis (muscle break down) hyperthermia

238
Q

nonspecific signs of malignant hyperthermia

A

tachycardia, tachypnea, acidosis, hyperkalemia

239
Q

What is given to malignant hyperthermia patients

A

Dantroelene 2.5 mg/kg to close RyR channel

240
Q

Muscular Dysgenesis

A

lack of DHPR in skeletal muscle

241
Q

Myostatin deficient

A

mutation that lacks control of skeletal muscle growth. Causes huge muscles
possible treatment for Duchenne muscular dystrophy

242
Q

Muscular Dystrophy - Duchenne

A

cardiac myopathy is most common cause of death
high creatinine levels 1000s
mutation in dystrophin

243
Q

Rigor Conformation

A

myosin is stuck to Actin because not enough ATP is represent for release

244
Q

Cardiac E-C Coupling

A

same as skeletal, but Ca release is required from DHPR to bind to Ryr to trigger Ca release

245
Q

E-C coupling in smooth

A

so thin that Ca easily diffuses throughout cell during entry

246
Q

Motor units

A

muscle fibers innervated by a single motor neuron

vary in size depending on movement required.

247
Q

Muscle fiber types

A

due to isoenzyme variation, myosin variation, proportion of mitochondira, oxidative enzymes, resistance to fatigue, speed of contraction

248
Q

Slow Muscle fibers

A

maintained contraction

Red in color due to myoglobin content

249
Q

Fast muscle fibers

A

high glycolytic content

rapid bursts of activity

250
Q

Intermediate fibers

A

both glycolytic and oxidative enzymes

251
Q

Gradiation of Tension

A

Increase frequency of AP
Recruitment of motor units
(smooth and cardiac depend on NT and hormone-like molecules)

252
Q

Satellite cells

A

stems cells that are source of new myoblasts to repair injured muscle.
responsible to fibroblast growth factor, insulin GF, hepatocyte GF, NFKB, NO, myostatin
LIF tirggers proliferation
IL6 is secreted by exercise and triggers satellite cells.

253
Q

Cardiac and Smooth muscle repair

A

fibroblasts generate scar tissue in heart

smooth cells dedifferentiate and enter mitosis to regenerate new muscle cells

254
Q

changes to muscle with exercise

A

increases cross section
increase myosin and actin, but cells to not replicate.
NO real change in fast vs slow twitch, thus athletes are born not made.

255
Q

Fatigue in muscles

A

(1) decreased propagation of the action potential into the t tubule
(2) decreased release of Ca+2 from the SR,
3) reduced effect of Ca+2 on the myofilament interaction
(4) elevated hydrogen and phosphate reduced force generation by the myofilaments

M2M Unit 4 (1 decks)

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