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PHYL 4504 > Epithelial Transport > Flashcards

Epithelial Transport Flashcards

1
Q

What are the functions of epithelial cells?

A

protection, sensation, ion transport and fluid secretion, secretion of chemical mediators, nutrient absorption, excretion, diffusion

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2
Q

3 basic units in epithelial structure:

A

cells, tight junctions, basement membrane

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3
Q

epithelial cells are:

A

polarized - distinct domains

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4
Q

apical vs basolateral

A

facing the lumen vs facing interstitial space

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5
Q

what is the BM composed of and what does it do?

A

protein fibers, connects epithelial tissue to underlying connective tissues and provides support

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6
Q

Tight junctions…

A

for every Na transported, an anion must also be transported - this depends on permeability of tight junction

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7
Q

WHat do tight junctions do?

A

act as a barrier to migration of apical membrane proteins to basolateral membrane, act as a fence to maintain polarity, binds epithelium together = structural support, constitutes an extracellular route for movement of electroyltes

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8
Q

EPithelial permeability is a hallmark of what?

A

mucosal inflammation

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9
Q

Apical Junction Complexes (AJC) play an important role in what?

A

epithelial defence

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10
Q

AJCs are made up of…

A

Tight junctions and adherens junctions

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11
Q

TJ regulate

A

paracellular transport of ions and molecules

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12
Q

AJ important for

A

initiation and maintenance of cell cell adhesion

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13
Q

Dysfunction of epithelial junctions is linked to what?

A

airway disease and may predispose to infections

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14
Q

Barrier function normally studied by??

A

Growing cells on semi premeable membrane supports - this has strengths and weaknesses

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15
Q

Junction function measured by..?

A

permeability to small ions and analyzing TEER, using permeability probes of different sizes and measuring flux

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16
Q

Apparent Flux =

A

Flow rate (surface area X starting concentration)

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17
Q

molecules that cross paracellularly via TJs should show..?

A

linear and non saturable permeability

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18
Q

TJ proteins

A

claudins, Ig like proteins aka JAM and CAR, MARVEL proteins like occludin, tricellulin and MARVELD3

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19
Q

AJ proteins

A

Cadherins plus associated catennins

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20
Q

In the cytosol there is what protein that link the intracellular domains of TJ components with actin binding proteins?

A

Zonula Occludens (ZO)

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21
Q

Intact epithelial junctions prevent..?

A

inappropriate ligand/receptor interactions

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22
Q

barrier dysfunction allows for

A

penetration of particles and anitgens into subeptiehlial space where they encounter immune cells

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23
Q

Three mechanisms of inducible AJC dysfunciton, not mutually exclusive

A
  1. Apical junction degraded by extracellular proteases released by inflammatory cells. 2. AJP component expression can be silenced at transcirptional or post transcirptional level. 3. JUnction complexes can be disrupted via internalization or shedding of AJP components
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24
Q

3 things that cause junction dysfunciton in airways

A

Air pollution, respiratory virus, cystic fibrosis - all decrease TEER

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25
Q

What dsitinguishes an epithelial cell from other cell types?

A

Polarity - ability to segregate different but complimentary proteins between two distinct membrane domains

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26
Q

Polarity is made possible by

A

Tight junctions

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27
Q

becuase of polarity, these cells can perform

A

vectoral transport

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28
Q

two pathways for movement -

A

paracellular and transcellular

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29
Q

EPithelia can also perform selective

A

absorption and secretion

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30
Q

Sodium Potassium ATPase located

A

basolateral membrane, 3 Na out, 2 K+ in

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31
Q

basolateral membrane voltage is

A

negative and predominantely K+ conductive

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32
Q

intracellular concentrations of K+, Na_, and Cl-

A

100 mM, 10-25mM, 15-25mM

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33
Q

transepithelial transport of Na incolces

A

primary active transport

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34
Q

Na movement into the cell is always:

A

downhill via ENaC

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35
Q

net sodium movement produces elevated osmolarity on that side and decrease osmolarity in the lumen which results in

A

osmotic flow of water across epithelium in same direction as net solute movement

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36
Q

Categorizing epithelium as

A

absorptive or secretory and leaky or tight

37
Q

Resistance is

A

opposition to the passage of an electric current

38
Q

there is an inverse relationship between transeptiehlial resistance and

A

ionic permeability

39
Q

Net transepithelial resistance given by:

A

Rt = RcRpc/Rc+Rpc

40
Q

leaky epithelium has ___ resistance TJs

A

low resistance

41
Q

tight epithelia has ___ resistance TJs

A

high resistance

42
Q

How do you study transepithelial ion movement?

A

Ussing Chamber

43
Q

The short circuit current is:

A

the current that is required to reduce Vt to zero

44
Q

lsc is

A

charge flow per unit time when the tissue is short circuited (Vt = 0mV)

45
Q

electrical resistance Rt is calculated from

A

Ohm’s Law Rt = change in V/ change in I

46
Q

Vt is the voltage difference between the

A

apical and basolateral bahting solutions

47
Q

Electrogenic Na transport

A

through ENaC and Na pump, Cl paracellularly, Absorption

48
Q

Active Cl secretion

A

NKCC and CFTR, Na paracellularly, Secretion

49
Q

ENaC consists of how many subunits, and what are they?

A

3, alpha, beta and gamma

50
Q

airway epithelia absrob Na via

A

amiloride sensitive electrogenic transport

51
Q

ENaC is important for the maintenance and composition of

A

ASL

52
Q

which subunits are expressed in type 2 alveolar cells?

A

alpha and gamma, not beta

53
Q

what does the heterogeneity of ENaC along airway surface suggest

A

differential regulation of liquig absorption by channels of various subunit composition

54
Q

CFTR dysfunciton is linked to what?

A

increase in ENaC activity

55
Q

Why is ENaC important for fluid clearance?

A

at birth, important to clear liquid from alveoli, alpha ENaC knowckout mice die at birth, reduced alpha ENaC expression results in delayed resolution of pulmonary edema after injury

56
Q

What is the predominant ion transport pathway present in alveolar epithelium?

A

Na+, dominant mechanism of alveolar liquid clearance

57
Q

Na enters via ___ and exits the basolateral membrane by _____

A

ENaC and Na-K ATPase

58
Q

ENaC is inhibited by

A

amiloride

59
Q

Na transport can be regulated by increasing what?

A

ENaC gene expression by glutocorticoids

60
Q

ENaC must be ___ by what to be active?

A

cleaved by intracellular furin type or extracellular serine proteases

61
Q

protease inhibitors lead to

A

silent ENaC - sits in membrane until proteolytically cleaved

62
Q

Claved by 3 things -

A

intracellular convertase type proteases, extracellular cell attached proteases, soluble proteases such as trypsin and neurophil elastase

63
Q

What happens after cleavage of ENaC?

A

inhibitor regions of e/c loops are the alpha and gamma subunits are removed

64
Q

Most important ion transport process of alveolar epithelial cells is

A

active sodium transport from alveolar lining fluid into interstitum

65
Q

Na moves _____ electrochemical gradient created via _____

A

down, Na pump

66
Q

Cl moves ___

A

paracellularly

67
Q

Na transport is critical for?

A

re-absorption of edema fluid following alveolar flooding

68
Q

Patient with ALI and ARDS have higher morbidity and mortality if…

A

alveolar fluid clearance mechanisms are imparied

69
Q

Pulmonary edema is caused by???

A

cardiac failure or gdamage to alveolar cells

70
Q

Reactive oxygen species can ____ Na transport and ____

A

decrease, fluid clearance

71
Q

infection with what can inhibit Na transport/liquid movement

A

Pseudomonas aeruginosa

72
Q

ALI stands for

A

Acute Lung Injury

73
Q

ARDS

A

Acutre respiratory distress syndrome

74
Q

Both ALI and ARDS are chacrterized by

A

acute inflammation that affects gas exchange

75
Q

ALI and ARDS can result from 2 things..?

A

direct pulmonary injury (pneumonia) or indirect blood borne insults (spesis)

76
Q

What does ARDS present with clinically?

A

breathlessness and pulmonary edema

77
Q

What distinguishes ALI from ARDS

A

severity of hypoxemia

78
Q

VALI?

A

ventilatory associated lung injury - high mortality rates

79
Q

Pathophysiology Early phase is associated with

A

acute inflammation of alveolar capillary membrane, necorsis of type 1 cells denudes BM causing hyaline membrane, protein rich edema fluid in intersitium and alveolus, inflammation associated with activated neutrophuls and alveolar macrophages which secrete inflammatory mediators

80
Q

what do inflammatory mediators do in ALI/ARDS?

A

impair durfactant production by ATII

81
Q

neutrophils are activated by what?

A

cytokines - TNF-alpha, IL-1, 6, and 8

82
Q

What else occurs?

A

thrombosis and extravascular fibrin deposition

83
Q

VALI can further the problem by…

A

inducing release of more proinflammatory cytokines

84
Q

Name a symptom of ALI

A
  1. protein rich hyaline membrane
  2. neutrohpils adhere to capillary endothelium and migrate to alveolus
  3. loss of membrane integrity
  4. impaired surfactant secretion
  5. capillary microthrombi and extravascular deposition
  6. increase pulmonary dead space
  7. hypoxemia
85
Q

Do most patients recover from acute inflammatory phase?

A

yes

86
Q

How do people recover?

A

type 2 cells proliferate in response to epithelial GF to recover the denuded BM, type 2 cells are progenitors for noth type 1 and 2, epithelial barrier is restored, hyaline membrane is phagocytosed by macrophages

87
Q

If lung injury is too severe or epithelial repair is impaired what happens?

A

fibroproliferative phase can develop - mesenchymal cells proliferate, neovascularization, alveolar space gets filled with fibroblasts that make collagen, thickening walls

88
Q

What marks the final stage of ALI/ARDS

A

intra-alveolar fibrosis - decreases compliance, sevrer hypozia and ventilatory dependence, lung scarring, cyst development

PHYL 4504 (8 decks)

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