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PHYSIOLOGY > Prelims - INTESTINAL FLUID AND ELECTROLYTE MOVEMENT (Dr. Salumbides) > Flashcards

Prelims - INTESTINAL FLUID AND ELECTROLYTE MOVEMENT (Dr. Salumbides) Flashcards

1
Q

These regulate both epithelial transport and motor activity during both the interdigestive and postprandial periods.

A

Enteric Neurons, as well as Endocrine and Paracrine Agonists

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2
Q

ABSORPTION of dietary nutrients is an exclusive function of

A

Small Intestine

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3
Q

What absorbs fluid and electrolytes

A

Both Small Intestine and Large Intestine

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4
Q

The SI has a _________, whereas

the Colon has __________ with __________.

A

Villous-crypt Organization
Surface Epithelial Cells
Interspersed Crypts

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5
Q

The SI cosist of finger-like projections ________ surrounded by openings of glandular structures called __________

A

Villi

Crypts of Lieberkühn, or simply Crypts

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6
Q

The cells lining the VILLI are considered to be the primary cells responsible for

A

Both nutrient and electrolyte absorption

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7
Q

CRYPT CELLS primarily participate in

A

Secretion

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8
Q

TRUE or FALSE

The colon has a villi

A

FALSE

  • Colon does not have a villi, instead the cells lining the large intestine are SURFACE EPITHELIAL CELLS, and interspersed over the colonic surface are numerous APERTURES OF COLONIC CRYPTS (OR GLANDS)
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9
Q

The SURFACE EPITHELIAL CELLS of the colon are the primary cells responsible for

A

Colonic electrolyte absorption

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10
Q

The COLONIC GLAND CELLS are generally believed to

A

Mediate ion secretion

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11
Q

The ZONE OF CELL PROLIFERATION is at the

A

Base of the Crypt

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12
Q

TRUE or FALSE

The intestinal mucosa is a dynamic organ with continuous cell proliferation and migration

A

TRUE

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13
Q

This is a stem cell that differentiates into several specialized cells (e.g., vacuolated, goblet and Paneth cells)

A

Progenitor cells

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14
Q

The __________ migrates along the crypt-villus axis and becomes a villous absorptive cell after undergoing substantial changes in its morphological and functional characteristics.

A

Vacuolated cell

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15
Q

The overall period from initiation of cell proliferation to sloughing is

A

48-96 hrs

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16
Q

DECREASED cell turnover occurs during

A

Fasting

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17
Q

INCREASED cell turnover occurs during

A

Feeding and Lactation

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18
Q

Length (m) of SI and Colon

A

6

2.4

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19
Q

Area of apical plasma membrane (m2) for SI and Colon

A

~ 200

~ 25

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20
Q

YES or NO

Villi in COLON

Nutrient Absorption in COLON

Microvilli in COLON

Active Na Absorption in COLON

Active K Secretion in SI

Active K Secretion in COLON

Active Na Absorption in SI

Microvilli in SI

A 
NO
NO
YES
YES
NO
YES
YES
YES
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21
Q

The SI is amplified at three levels

A

(1) Folds of Kerckring
(2) Villi and Crypts
(3) Microvilli

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22
Q

The Colon is amplified at three levels

A

(1) Semilunar folds
(2) Crypts (but NOT VILLI)
(3) Microvilli

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23
Q

Thus, if the SI is thought of as a hollow cylinder, the net increase in total surface area of the small intestine (versus that of the smooth cylinder) is

A

600-fold

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24
Q

The fluid content of average diet is typically

A

1.5 - 2.5 L/day

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25
Q

Fluid load to the small intestine is

A

8 - 9 L/day

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26
Q

Calculate absorption of water and electrolytes from small intestine

A

Total load presented to lumen of SI - Fluid leaving the SI (Ileocecal flow)

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27
Q

In normal subjects, the fluid leaving the small intestine (Ileocecal flow) is

A

2.0 L/day

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28
Q

The overall small-intestinal water absorption

A
  1. 5 L/day

* Na+ absorption is 600 mmol/day

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29
Q

Maximal small-intestinal fluid absorption is

A

15 to 20 L/day

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30
Q

Measure Colonic fluid absorption

A

Difference between Ileocecal flow and Stool water

  • Stool water is usually 0.1 L/day
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31
Q

Colonic water absorption is about

A

1.9 L/day

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32
Q

The maximal colonic water ABSORPTIVE CAPACITY

A

4 and 5 L/day

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33
Q

Inflow from saliva is

A

1.5 L/day

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34
Q

Presented to lumen of small intestine

A

8.5 L/day

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35
Q

Secreted by small intestine

A

1L/day

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36
Q

The SI absorbs net amounts of __________ and secretes __________, whereas the COLON absorve net amounts of __________ and secretes __________

A

Water, Na+, Cl-, K+

HCO3-

Water, Na+, Cl-

K+, HCO3-

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37
Q

Fluid and electrolyte transport in the intestine varies considerably in two different axes

A

(1) Along the length of intestines (SEGMENTAL HETEROGENEITY)
* comparison between two different segments of the intestine (duodenum versus ileum)
(2) From the bottom a crypt to a top of a villus or to the surface cells (CRYPT-VILLUS/SURFACE HETEROGENEITY)

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38
Q

Finally, at a certain level within a single villus or crypt - or within a very small area of colonic surface epithelium - individual cells may demonstrate further heterogeneity

A

Cellular Heteregenity

  • with specific transport mechanisms restricted to different cells
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39
Q

SMALL INTESTINE is a NET ABSORBER of

but is a NET SECRETOR of

A

Water, Na+, Cl- and K+

HCO3-

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40
Q

TRUE or FALSE

The absorptive process in the small intestine are enhanced in the postprandial state

A

TRUE

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41
Q

The HUMAN COLON carries out NET ABSORPTION of

but it carries out NET SECRETION of

A

Water, Na+ and Cl-

K+ and HCO3-

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42
Q

In __________, the solute must cross the two cell membrane in series, and at least one of these membranes must be active (i.e., against an electrochemical graduent)

A

Transcellular Movement

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43
Q

In __________, the solute move passively between adjacent epithelial cells through the tight junctions.

A

Paracellular Movement

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44
Q

TRUE or FALSE

All trancellular Na+ absorprtion is mediated by Na-K pump located at apical membrane

A

FALSE

  • All trancellular Na+ absorprtion is mediated by Na-K pump located at BASOLATERAL membrane
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45
Q

TRUE OR FALSE

Fluid movement is always coupled to active solute movement

A

TRUE

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46
Q

Water movement occurs predominantly by __________ route

A

Paracellular

  • and it depends on the PERMEABILITY PROPERTIES OF THE TIGHT JUNCTIONS and the MAGNITUDE OF THE CONVECTIVE WATER FLOW

(P.M.)

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47
Q

Solute movement may also be coupled to fluid movement by

A

Solvent Drag

  • a phenomenon in which the dissolved solute is swept along by bulk movement of the solvent (e.g., water)
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48
Q

Solvent gmdrag occurs through the __________ route

A

Paracellular

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49
Q

TRUE OR FALSE

Solvent drag accounts for a significant fraction of Na+ and Urea absorbed in the human ileum

A

FALSE

  • Solvent drag accounts for a significant fraction of Na+ and Urea absorbed in the human JEJUNUM (but not in the more distal segments of the small intestine or the large intestine)
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50
Q

TRUE OR FALSE

The transepithelial permeability of the jejunum is considerably greater than
that of the ileum or colon

A

TRUE

  • solvent drag contributes primarily to the absorption of relatively small, water-soluble molecules, such as UREA and NA+
  • as evidenced by its:

(1) lower spontaneous transepithelial voltage difference (Vte)
(2) higher passive movement of NaCl
(3) larger apparent pore size

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51
Q

The RESISTANCE OF THE TIGHT JUNCTIONS primarily determines the ___________ of intestinal epithelia

A

Transepithelial Resistance

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52
Q

Epithelial permeability is an _________ of transepithelial resistance.

A

Inverse function

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53
Q

Transepithelial resistance is determined by

A

(1) Cellular Resistance
(2) Paracellular Resistance

(C.P.)

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54
Q

TRUE OR FALSE

Paracellular resistance is considerably lower than Transcellular resistance

A

TRUE

*therefore, overall mucosal resistance primarily reflects PARACELLULAR RESISTANCE, which in turn depends primarily on the properties of tight junctions

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55
Q

TRUE OR FALSE

Resistance increases in the ABORAL DIRECTION (ie., moving away from the mouth)

A

TRUE

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56
Q

TRUE OR FALSE

The permeability of tight junctions in the crypt is lesser than that in the villus.

A

FALSE

  • The permeability of tight junctions in the crypt is GREATER than that in the villus.
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57
Q

____________ in the small intestine is a major mechanism for postprandial Na+ absorption

A

Na/glucose and Na/amino-acid cotransport

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58
Q

Glucose and amino acid-coupled Na+ absorption is mediated by specific apical transport protein called

A

Na/glucose contransporter SGLT1

  • responsible for glucose uptake across the apical membrane
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59
Q

The transporter process for Na/glucose and Na/amino acid cotransport are examples of

A

SECONDARY ACTIVE TRANSPORT

  • because these transporters couple the energetically downhill movement of Na+ to the uphill movement of glucose or amino acid
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60
Q

Glucose- and amino acid- stimulated Na+ absorption is an _________ process

A

Electrogenic

  • because the apical Na/glucose and Na/amino-acid cotransporters are electrogenic, as is the Na-K pump, the overall transport of Na+ carries net charge and makes Vte more lumen negative
  • the increase in the lumen-negative Vte provides the driving force for the parallel absorption of Cl-
61
Q

TRUE OR FALSE

Nutrient-coupled Na+ transporters are not inhibited by either cAMP or [Ca2+]

A

TRUE

  • thus agonists that increase cAMP or Ca2+ do not inhibit glucose- or amino acid- stimulated Na+ absorption
62
Q

Nutrient-coupled Na+ absorption occurs in the villous cells of the

A

Jejunum and Ileum

63
Q

Electroneural Na-H exchange un the __________ is responsible for Na+ absorption that is stimulated by __________

A

Duodenum and Jejunum

  • NaCl absorption occurs in the ileum and throughout the large intestine, with the EXCEPTION OF THE MOST DISTAL SEGMENT

Luminal Alkalinity

  • Luminal Alkalinity is the result of pancreatic, biliary and duodenal secretion
64
Q

Na+ uptake across the apical membrane to proton extrusion into the intestinal lumen is a process enhanced by both

A

Decreases in intracellular pH (pHi)

Increases in luminal pH

65
Q

Electroneural Na-H exchange is inhibited by

A

MILLIMOLAR concentratuons if the diuretic AMILORIDE

66
Q

TRUE OR FALSE

Several isoforms of the Na-H exchanger exists

67
Q

describe NHE 1 ISOFORM

A
  • BASOLATERAL MEMBRANE

- Regulates pH (“housekeeping” function) and does not contribute to the transepithelial movement of Na+

68
Q

describe both NHE2 and NHE3 exchanger isoforms

A
  • APICAL MEMBRANE

- responsible for transepithelial Na+ movement and pH regulation

69
Q

TRUE OR FALSE

Only in the duodenum and jejunum is Na-H exchange present without the parallel presence of Cl-HCO3 exchangers

70
Q

Parallel Na-H and Cl-HCO3 exchange in the _________ is the primary mechanism of Na+ absorption during the __________

A

Ileum and Proximal Part of the Colon

Interdigestive period

71
Q

In the human colon, DRA (downregulated-in-adenoma) mediates

A

Cl-HCO3 exchange

72
Q

TRUE OR FALSE

Parallel Na-H and Cl-HCO3 exchange is affected by either luminal glucose or luminal HCO3-

A

FALSE

  • NOT AFFECTED
73
Q

The overall NaCl absorptive process is under the control of both

A

cAMP and cGMP, as well as intracellular Ca2+

  • INCREASES in each of these three REDUCE NaCl absorption
  • DECREASES in Ca2+ and INCREASES in Aldosterone INCREASE NaCl absorption
74
Q

Epithelial Na+ channels are the primary mechanism of __________ Na+ absorption in the __________

A

Electrogenic

Distal part of the colon

75
Q

In electrogenic Na+ absorption, Na+ entry across the apical membrane occurs through

A

Epithelial Na+ channels (ENaCs)

76
Q

ENaCs are blocked by

A

MICROMOLLAR concentrations of the diuretic AMILORIDE

77
Q

TRUE OR FALSE

The distal segment of the colon is capable of absorbing Na+ against large concentration gradients

A

TRUE

  • it plays an important role in Na+ conservation
78
Q

TRUE OR FALSE

Na+ movement via electrogenic Na+ absorption is affected by luminal glucose or by HCO3-, nor it is regulated by cyclic nucleotides.

A

FALSE

  • Na+ movement via electrogenic Na+ absorption is NOT AFFECTED by luminal glucose or by HCO3-, nor it is regulated by cyclic nucleotides.
79
Q

Na+ movement via electrogenic Na+ absorption is markedly enhanced by

A

Corticoids (Aldosterone)

80
Q

Aldosterone increases electrogenic Na+ absorption by

A

(1) Increasing entry through apical Na+ channel
(2) Stimulating activity of the Na-K pump

  • INCREASE IN APICAL Na+ UPTAKE CAN OCCUR:

(1) RAPIDLY (within seconds), as a consequence of an increase in the opening of apical Na+ channels
(2) MORE GRADUALLY (within minutes), because of the insertion of preformed Na+ channels from subapical epithelial vesicle pools into the apical membrane
(3) VERY SLOWLY (within hours) as a result of an increase in the synthesis of both new apical Na+ channels and Na-K pumps

81
Q

Voltage dependent Cl- absorption represents coupling of Cl- absorption to __________ in both the small intestine and the large intestine

A

Electrogenic Na+ absorption

82
Q

The driving force for Cl- absorption derives from either of the two electrogenic mechanisms of Na+ absorption

A

(1) Nutrient-coupled transport in the SMALL INTESTINE

[induction of a lumen-negative potential difference by glucose- and amino acid- induced Na+ absorption provides the driving force for Cl- absorption that occurs following a meal]

(2) ENaC channels in the DISTAL END OF COLON

[lumen-negative potential difference that provides the driving force for colonic voltage-dependent Cl- absorption]

*this process is referred to as VOLTAGE-DEPENDENT Cl- ABSORPTION (it is not an active transport process)

83
Q

TRUE OR FALSE

Most likely the route of voltage-dependent Cl- absorption is transcellular

A

FALSE

  • PARACELLULAR
84
Q

The congenital absence of an apical Cl-HCO3 exchanger

A

Congenital Chloridorrhea OR Congenital Cl- Diarrhea (CDL)

  • Autosomal Recessive
  • Located in chromosome band 7q31
  • Excessively high stool [Cl-]
  • Because HCO3- secretion is reduced, patients are ALKALOTIC [increased plasma HCO3-]
85
Q

Electroneutral Cl-HCO3 exchange results in Cl- absorptuon and HCO3- secretion in the __________

A

Ileum and Colon

86
Q

Cl- movement across the basolateral membrane are not well understood, but the process may involve

A

ClC-2 Cl- channel

87
Q

Parallel Na-H and Cl-HCO3 exchange in the _________ mediates Cl- absorption during the __________

A

Ileum and Proximal Part of the Colon

Interdigestive Period

88
Q

Electroneutral NaCl absorption, discussed in connection with Na+ absorption, also mediates Cl- absorption in the ileum and proximal part of the colon, the apical step of Cl- absorption by this mechanism is mediated by

A

Parallel Na-H exchange and Cl-HCO3 exchange

  • which are COUPLED THROUGH pH
89
Q

The cellular model of active Cl- secretion includes three transport pathways on the BASOLATERAL MEMBRANE

A

(1) Na-K pump
(2) Na/K/Cl cotransporter
(3) two types of K+ channels

  • in addition, CFTR channel is also present on APICAL MEMBRANE
90
Q

The complex Cl- entry across the basolateral membrane is energized by the

A

Na-K pump

  • which generates a low Na+ and provides the driving force for Cl- entry across the basolateral membrane through Na/K/Cl contransport
  • as a result, Cl- is raised sufficiently that the Cl- eldctrochemical gradient favors the passive efflux of Cl- across the apical membrane
  • TRANSEPITHELIAL VOLTAGE becomes more lumen negative, which promotes voltage-dependent Na+ secretion, this Na+ secretion accompanies Cl- secretion presumably occurs through tight junctions (paracellular pathway)
  • Thus, the net result is stimulation of NaCl and fluid secretion
91
Q

The resulting activation of one or more protein kinases - by any of the aforementioned pathways - increases the Cl- conductance of the apical membrane either by

A

(1) Activating pre-existing Cl- channels

(2) Inserting into the apical membrance Cl- channels

92
Q

Cl- now exits the cell through apical Cl- channels; the result is a decrease in [Cl-], which leads to increased uptake of __________ across the BASOLATERAL MEMBRANE via ________.

A

Na+, Cl- and K+

NKCC1

  • Na+ recycles out of the cell via the Na-K pump
  • K+ recycles through basolateral K+ channels
93
Q

Second Messenger for CHOLERA TOXIN

94
Q

Second Messenger for VIP

95
Q

Second Messenger for HISTAMINE

96
Q

Second Messenger for E. COLI (Heat Labile)

A

Second Messenger for cAMP

97
Q

Second Messenger for CLOSTRIDIUM DIFFICILE TOXIN

98
Q

Second Messenger for E. COLI (Heat Stable)

99
Q

Second Messenger for YERSINIA TOXIN

100
Q

Second Messenger for GUANYLIN

101
Q

Second Messenger for PROSTAGLANDINS

102
Q

Second Messenger for ACETYLCHOLINE

103
Q

Second Messenger for BRADYKININ

104
Q

Second Messenger for SEROTONIN (5-HT)

105
Q

Overall net transepithelial K+ movement is _________ in the small intestine and ___________ in the colon

A

Absorptive

Secretory

106
Q

The intestines absorb K+ in the _________ but secrete it in the _________

A

PROXIMAL SEGMENTS

DISTAL SEGMENTS

107
Q

Dietary K+ furnishes ________; whereas stool K+ output is only _______

A

80 to 120 mmol/day

10 mmol/day

108
Q

The concentration of K+ in stool is frequently

109
Q

TRUE OR FALSE

Total K+ load presented to the small intestine is considerably lesser than that represented by the diet.

A

FALSE

Total K+ load presented to the small intestine is considerably GREATER than that represented by the diet.

110
Q

K+ absorption in the small intestine probably occurs via __________

A

Solvent Drag

111
Q

K+ is absorbed in the ___________ of the small intestine and is secreted in the __________.

A

Jejunum and Ileum

Large Intestine

112
Q

TRUE OR FALSE

Na+ and K+ and alterations in hydration influence K+ movement in Colon

A

TRUE

  • Similar physiological events do not appear to affect K+ absorption in small intestine
113
Q

Passive K+ secretion is the primary mechanism for _________

A

Net colonic secretion

114
Q

This pathway is primarily responsible for overall net colonic K+ secretion

A

Passive K+ secretion

  • route is PARACELLULAR
115
Q

Passive K+ secretion is driven by the lumen-negative Vte of

A

15 to 25 mV

116
Q

TRUE OR FALSE

Passive K+ secretion is greatest in the distal end of the colon

A

TRUE

  • this is where Vte difference is most negative
  • increases in lumen-negative Vte that occur as as an adaptive response to dehydration - secondary to an elevation in aldosterone secretion result in an enhanced rate of passive K+ secretion
117
Q

Active K+ secretion is also present throughout the _______ and is induced both by ________

A

Large Intestine

Aldosteron and cAMP

118
Q

Active K+ absorption is present only in the

A

Distal part of the colon

119
Q

The general paradigm of active K+ transport in the colon is a

A

“pump-leak model”

120
Q

When APICAL K+ CHANNEL ACTIVITY IS LESS THAN BASOLATERAL CHANNEL ACTIVITY

A

K+ recycling dominates

121
Q

________ stimulates active K+ secretion in surface epithelial cells

A

Aldosterone

122
Q

________ stimulates active K+ secretion in crypt cells

123
Q

Aldosterone (Mineralocorticoid) enhances overall K+ secretion by two mechanisms

A

(1) Enhances PASSIVE K+ SECRETION by increasing Na-K pump activity and thus increasing electrogenic Na+ absorption
* net effects are to increase the lumen-negative Vte and to enhance passive K+ secretion
(2) Stimulates ACTIVE K+ SECRETION by increasing the activity of both apical K+ channels and basolateral Na-K pumps

124
Q

How does cAMP AND Ca2+ stimulate active K+ secretion

A

increase activity of both apical and basolateral K+ channels

  • neither of these has an effect on the Na-K pump
  • because stimulation of K+ channels is greater at the apical than at the basolateral membrane, the result is an increase in K+ exit from the epithelia cell across the apical membrane
  • stimulation of K+ secretion by cAMP and Ca2+ also induce active Cl- secretion
125
Q

Active K+ absorption takes place only in the ________ and is energized by an _________

A

Distal portion of the colon

Apical H-K pump

126
Q

TRUE OR FALSE

Increases in dietary K+ enhance both passive and acyive K+ secretion

A

TRUE

  • dietary K+ depletion enhances active K+ absorption
127
Q

Mechanism of active K+ absorption

A

Exchange of luminal K+ for intracellular H+ across the apical membrane, mediated by an H-K pump

  • Active K+ absorption occurs via a TRANSCELLULAR ROUTE
128
Q

Chemical mediators from the ENS, endocrine cells and immune cells in the _________ may be either secretagogues or absorptagogues

A

Lamina Propria

129
Q

The _______ is important in the normal regulation of intestinal epithelial electrolyte transport

130
Q

Activation of enteric secretomotor neurons results in the

A

Release of Ach from mucosal neurons and in the induction of active Cl- secretion

131
Q

Example of ENDOCRINE SYSTEM

A

Release of aldosterone from adrenal cortex and subsequent formation of Angiotensin II

  • stimulate Na+ absorption, ANGIOTENSIN in Small Intestine (Electroneutral NaCl Absorption) and ALDOSTERONE in the Colon (Electrogenic Na+ Absorption)
132
Q

Example of PARACRINE REGULATION

A

Immune cells in the lamina propria

133
Q

Product of Macrophages

A

Prostaglandins

02 Radicals

134
Q

Product of Mast Cells

135
Q

Product of Neutrophils

A

Eicosanoids

Platelet-activing factor

136
Q

Product of Fibroblasts

A

Eicosanoids

Bradykinin

137
Q

Secretagogues can be classified by their __________ and by the _________

A

Type

Intracellular second-messenger system that they stimulate

138
Q

Peptide that is produced and excreted by bacteria that can produce effects independently of the bacteria

A

Bacterial exotoxin

139
Q

An exotoxin that induces changes in intestinal fluid and electrolyte movement

A

Enterotoxin

140
Q

Explain mechanism of E. Coli HEAT-LABILE toxin

A

Apical membrane receptors —> Internalized —> Activates BASOLATERAL Adenylyl Cyclase —> Increase cAMP —> Activates Protein Kinase A

  • VIP also acts by this route
141
Q

Explain mechanism of E. Coli HEAT-STABLE toxin

A

Apical membrane receptors —> Internalized —> Activates APICAL Guanylyl Cyclase —> Increase cGMP —> Activates Protein Kinase G * and may also activate Protein Kinase A

  • ANP works similar
  • Agonist for this pathway is Guanylin, a 15-amino-acid peptide
142
Q

How do secretogogues increase Ca2+

A

Stimulating Phospholipase C —> Production of Inositol 1,4,5-Triphosphate (IP3) —> Release of Ca2+

  • secretogogues can also increase Ca2+ by activatingprotein kinases, which may stimulate Basolateral Ca2+ channels
143
Q

All three second messengers

A

Increase Anion Secretion

Inhibit NaCl Absorption

  • cGMP’s ability to stimulate Cl- secretion is somewhat LESS (+)
144
Q

Mineralocorticoids, Glucocorticoids and Somatostatin are ________

A

Absorptagogues

145
Q

Primary hormones that enhance intestinal fluid and electrolyte absorption

A

Corticosteroids

146
Q

These stimulate in Na+ absorption and K+ secretion in the distal end of the colon; they do not affect ion transport in the small intestine

A

Mineralocorticoids (e.g., Aldosterone)

  • induces both apical membrane N+ channels and basolateral Na-K pumps
147
Q

These stimulate electroneural NaCl absorption throughout the large and small intestine without any effect on either K+ secretion or electrogenic Na+ absorption

A

Glucocorticoids

  • both corticosteroids act at least in part by GENOMIC MECHANISMS
148
Q

Somatostatin as an absortagogue

A

Stimulates Electroneural NaCl absorption and inhibits electrogenic HCO3- secretions

  • released from endocrine cells in the intestinal mucosa
  • works the same with ENKEPHALINS and NOREPINEPHRINE
    (works by also decreasing Ca2+, probably by blocking Ca2+ channels)

PHYSIOLOGY (6 decks)

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