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
2
Q
ABSORPTION of dietary nutrients is an exclusive function of
A
Small Intestine
3
Q
What absorbs fluid and electrolytes
A
Both Small Intestine and Large Intestine
4
Q
The SI has a _________, whereas
the Colon has __________ with __________.
A
Villous-crypt Organization
Surface Epithelial Cells
Interspersed Crypts
5
Q
The SI cosist of finger-like projections ________ surrounded by openings of glandular structures called __________
A
Villi
Crypts of Lieberkühn, or simply Crypts
6
Q
The cells lining the VILLI are considered to be the primary cells responsible for
A
Both nutrient and electrolyte absorption
7
Q
CRYPT CELLS primarily participate in
A
Secretion
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)
9
Q
The SURFACE EPITHELIAL CELLS of the colon are the primary cells responsible for
A
Colonic electrolyte absorption
10
Q
The COLONIC GLAND CELLS are generally believed to
A
Mediate ion secretion
11
Q
The ZONE OF CELL PROLIFERATION is at the
A
Base of the Crypt
12
Q
TRUE or FALSE
The intestinal mucosa is a dynamic organ with continuous cell proliferation and migration
A
TRUE
13
Q
This is a stem cell that differentiates into several specialized cells (e.g., vacuolated, goblet and Paneth cells)
A
Progenitor cells
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
15
Q
The overall period from initiation of cell proliferation to sloughing is
A
48-96 hrs
16
Q
DECREASED cell turnover occurs during
A
Fasting
17
Q
INCREASED cell turnover occurs during
A
Feeding and Lactation
18
Q
Length (m) of SI and Colon
A
6
2.4
19
Q
Area of apical plasma membrane (m2) for SI and Colon
A
~ 200
~ 25
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
21
Q
The SI is amplified at three levels
A
(1) Folds of Kerckring
(2) Villi and Crypts
(3) Microvilli
22
Q
The Colon is amplified at three levels
A
(1) Semilunar folds
(2) Crypts (but NOT VILLI)
(3) Microvilli
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
24
Q
The fluid content of average diet is typically
A
1.5 - 2.5 L/day
25
Fluid load to the small intestine is
8 - 9 L/day
26
Calculate absorption of water and electrolytes from small intestine
Total load presented to lumen of SI - Fluid leaving the SI (Ileocecal flow)
27
In normal subjects, the fluid leaving the small intestine (Ileocecal flow) is
2.0 L/day
28
The overall small-intestinal water absorption
6. 5 L/day
| * Na+ absorption is 600 mmol/day
29
Maximal small-intestinal fluid absorption is
15 to 20 L/day
30
Measure Colonic fluid absorption
Difference between Ileocecal flow and Stool water
* Stool water is usually 0.1 L/day
31
Colonic water absorption is about
1.9 L/day
32
The maximal colonic water ABSORPTIVE CAPACITY
4 and 5 L/day
33
Inflow from saliva is
1.5 L/day
34
Presented to lumen of small intestine
8.5 L/day
35
Secreted by small intestine
1L/day
36
The SI absorbs net amounts of __________ and secretes __________, whereas the COLON absorve net amounts of __________ and secretes __________
Water, Na+, Cl-, K+
HCO3-
Water, Na+, Cl-
K+, HCO3-
37
Fluid and electrolyte transport in the intestine varies considerably in two different axes
(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)
38
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
Cellular Heteregenity
* with specific transport mechanisms restricted to different cells
39
SMALL INTESTINE is a NET ABSORBER of
but is a NET SECRETOR of
Water, Na+, Cl- and K+
HCO3-
40
TRUE or FALSE
The absorptive process in the small intestine are enhanced in the postprandial state
TRUE
41
The HUMAN COLON carries out NET ABSORPTION of
but it carries out NET SECRETION of
Water, Na+ and Cl-
K+ and HCO3-
42
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)
Transcellular Movement
43
In __________, the solute move passively between adjacent epithelial cells through the tight junctions.
Paracellular Movement
44
TRUE or FALSE
All trancellular Na+ absorprtion is mediated by Na-K pump located at apical membrane
FALSE
* All trancellular Na+ absorprtion is mediated by Na-K pump located at BASOLATERAL membrane
45
TRUE OR FALSE
Fluid movement is always coupled to active solute movement
TRUE
46
Water movement occurs predominantly by __________ route
Paracellular
* and it depends on the PERMEABILITY PROPERTIES OF THE TIGHT JUNCTIONS and the MAGNITUDE OF THE CONVECTIVE WATER FLOW
(P.M.)
47
Solute movement may also be coupled to fluid movement by
Solvent Drag
* a phenomenon in which the dissolved solute is swept along by bulk movement of the solvent (e.g., water)
48
Solvent gmdrag occurs through the __________ route
Paracellular
49
TRUE OR FALSE
Solvent drag accounts for a significant fraction of Na+ and Urea absorbed in the human ileum
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)
50
TRUE OR FALSE
The transepithelial permeability of the jejunum is considerably greater than
that of the ileum or colon
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
51
The RESISTANCE OF THE TIGHT JUNCTIONS primarily determines the ___________ of intestinal epithelia
Transepithelial Resistance
52
Epithelial permeability is an _________ of transepithelial resistance.
Inverse function
53
Transepithelial resistance is determined by
(1) Cellular Resistance
(2) Paracellular Resistance
(C.P.)
54
TRUE OR FALSE
Paracellular resistance is considerably lower than Transcellular resistance
TRUE
*therefore, overall mucosal resistance primarily reflects PARACELLULAR RESISTANCE, which in turn depends primarily on the properties of tight junctions
55
TRUE OR FALSE
Resistance increases in the ABORAL DIRECTION (ie., moving away from the mouth)
TRUE
56
TRUE OR FALSE
The permeability of tight junctions in the crypt is lesser than that in the villus.
FALSE
* The permeability of tight junctions in the crypt is GREATER than that in the villus.
57
____________ in the small intestine is a major mechanism for postprandial Na+ absorption
Na/glucose and Na/amino-acid cotransport
58
Glucose and amino acid-coupled Na+ absorption is mediated by specific apical transport protein called
Na/glucose contransporter SGLT1
* responsible for glucose uptake across the apical membrane
59
The transporter process for Na/glucose and Na/amino acid cotransport are examples of
SECONDARY ACTIVE TRANSPORT
* because these transporters couple the energetically downhill movement of Na+ to the uphill movement of glucose or amino acid
60
Glucose- and amino acid- stimulated Na+ absorption is an _________ process
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
TRUE OR FALSE
Nutrient-coupled Na+ transporters are not inhibited by either cAMP or [Ca2+]
TRUE
* thus agonists that increase cAMP or Ca2+ do not inhibit glucose- or amino acid- stimulated Na+ absorption
62
Nutrient-coupled Na+ absorption occurs in the villous cells of the
Jejunum and Ileum
63
Electroneural Na-H exchange un the __________ is responsible for Na+ absorption that is stimulated by __________
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
Na+ uptake across the apical membrane to proton extrusion into the intestinal lumen is a process enhanced by both
Decreases in intracellular pH (pHi)
| Increases in luminal pH
65
Electroneural Na-H exchange is inhibited by
MILLIMOLAR concentratuons if the diuretic AMILORIDE
66
TRUE OR FALSE
Several isoforms of the Na-H exchanger exists
TRUE
67
describe NHE 1 ISOFORM
- BASOLATERAL MEMBRANE
| - Regulates pH ("housekeeping" function) and does not contribute to the transepithelial movement of Na+
68
describe both NHE2 and NHE3 exchanger isoforms
- APICAL MEMBRANE
| - responsible for transepithelial Na+ movement and pH regulation
69
TRUE OR FALSE
Only in the duodenum and jejunum is Na-H exchange present without the parallel presence of Cl-HCO3 exchangers
TRUE
70
Parallel Na-H and Cl-HCO3 exchange in the _________ is the primary mechanism of Na+ absorption during the __________
Ileum and Proximal Part of the Colon
Interdigestive period
71
In the human colon, DRA (downregulated-in-adenoma) mediates
Cl-HCO3 exchange
72
TRUE OR FALSE
Parallel Na-H and Cl-HCO3 exchange is affected by either luminal glucose or luminal HCO3-
FALSE
* NOT AFFECTED
73
The overall NaCl absorptive process is under the control of both
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
Epithelial Na+ channels are the primary mechanism of __________ Na+ absorption in the __________
Electrogenic
Distal part of the colon
75
In electrogenic Na+ absorption, Na+ entry across the apical membrane occurs through
Epithelial Na+ channels (ENaCs)
76
ENaCs are blocked by
MICROMOLLAR concentrations of the diuretic AMILORIDE
77
TRUE OR FALSE
The distal segment of the colon is capable of absorbing Na+ against large concentration gradients
TRUE
* it plays an important role in Na+ conservation
78
TRUE OR FALSE
Na+ movement via electrogenic Na+ absorption is affected by luminal glucose or by HCO3-, nor it is regulated by cyclic nucleotides.
FALSE
* Na+ movement via electrogenic Na+ absorption is NOT AFFECTED by luminal glucose or by HCO3-, nor it is regulated by cyclic nucleotides.
79
Na+ movement via electrogenic Na+ absorption is markedly enhanced by
Corticoids (Aldosterone)
80
Aldosterone increases electrogenic Na+ absorption by
(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
Voltage dependent Cl- absorption represents coupling of Cl- absorption to __________ in both the small intestine and the large intestine
Electrogenic Na+ absorption
82
The driving force for Cl- absorption derives from either of the two electrogenic mechanisms of Na+ absorption
(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
TRUE OR FALSE
Most likely the route of voltage-dependent Cl- absorption is transcellular
FALSE
* PARACELLULAR
84
The congenital absence of an apical Cl-HCO3 exchanger
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
Electroneutral Cl-HCO3 exchange results in Cl- absorptuon and HCO3- secretion in the __________
Ileum and Colon
86
Cl- movement across the basolateral membrane are not well understood, but the process may involve
ClC-2 Cl- channel
87
Parallel Na-H and Cl-HCO3 exchange in the _________ mediates Cl- absorption during the __________
Ileum and Proximal Part of the Colon
Interdigestive Period
88
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
Parallel Na-H exchange and Cl-HCO3 exchange
* which are COUPLED THROUGH pH
89
The cellular model of active Cl- secretion includes three transport pathways on the BASOLATERAL MEMBRANE
(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
The complex Cl- entry across the basolateral membrane is energized by the
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
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
(1) Activating pre-existing Cl- channels
| (2) Inserting into the apical membrance Cl- channels
92
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 ________.
Na+, Cl- and K+
NKCC1
* Na+ recycles out of the cell via the Na-K pump
* K+ recycles through basolateral K+ channels
93
Second Messenger for CHOLERA TOXIN
cAMP
94
Second Messenger for VIP
cAMP
95
Second Messenger for HISTAMINE
cAMP
96
Second Messenger for E. COLI (Heat Labile)
Second Messenger for cAMP
97
Second Messenger for CLOSTRIDIUM DIFFICILE TOXIN
Ca2+
98
Second Messenger for E. COLI (Heat Stable)
cGMP
99
Second Messenger for YERSINIA TOXIN
cGMP
100
Second Messenger for GUANYLIN
cGMP
101
Second Messenger for PROSTAGLANDINS
cAMP
102
Second Messenger for ACETYLCHOLINE
Ca2+
103
Second Messenger for BRADYKININ
Ca2+
104
Second Messenger for SEROTONIN (5-HT)
Ca2+
105
Overall net transepithelial K+ movement is _________ in the small intestine and ___________ in the colon
Absorptive
Secretory
106
The intestines absorb K+ in the _________ but secrete it in the _________
PROXIMAL SEGMENTS
DISTAL SEGMENTS
107
Dietary K+ furnishes ________; whereas stool K+ output is only _______
80 to 120 mmol/day
10 mmol/day
108
The concentration of K+ in stool is frequently
>100 mM
109
TRUE OR FALSE
Total K+ load presented to the small intestine is considerably lesser than that represented by the diet.
FALSE
Total K+ load presented to the small intestine is considerably GREATER than that represented by the diet.
110
K+ absorption in the small intestine probably occurs via __________
Solvent Drag
111
K+ is absorbed in the ___________ of the small intestine and is secreted in the __________.
Jejunum and Ileum
Large Intestine
112
TRUE OR FALSE
Na+ and K+ and alterations in hydration influence K+ movement in Colon
TRUE
* Similar physiological events do not appear to affect K+ absorption in small intestine
113
Passive K+ secretion is the primary mechanism for _________
Net colonic secretion
114
This pathway is primarily responsible for overall net colonic K+ secretion
Passive K+ secretion
* route is PARACELLULAR
115
Passive K+ secretion is driven by the lumen-negative Vte of
15 to 25 mV
116
TRUE OR FALSE
Passive K+ secretion is greatest in the distal end of the colon
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
Active K+ secretion is also present throughout the _______ and is induced both by ________
Large Intestine
Aldosteron and cAMP
118
Active K+ absorption is present only in the
Distal part of the colon
119
The general paradigm of active K+ transport in the colon is a
"pump-leak model"
120
When APICAL K+ CHANNEL ACTIVITY IS LESS THAN BASOLATERAL CHANNEL ACTIVITY
K+ recycling dominates
121
________ stimulates active K+ secretion in surface epithelial cells
Aldosterone
122
________ stimulates active K+ secretion in crypt cells
cAMP
123
Aldosterone (Mineralocorticoid) enhances overall K+ secretion by two mechanisms
(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
How does cAMP AND Ca2+ stimulate active K+ secretion
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
Active K+ absorption takes place only in the ________ and is energized by an _________
Distal portion of the colon
Apical H-K pump
126
TRUE OR FALSE
Increases in dietary K+ enhance both passive and acyive K+ secretion
TRUE
* dietary K+ depletion enhances active K+ absorption
127
Mechanism of active K+ absorption
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
Chemical mediators from the ENS, endocrine cells and immune cells in the _________ may be either secretagogues or absorptagogues
Lamina Propria
129
The _______ is important in the normal regulation of intestinal epithelial electrolyte transport
ENS
130
Activation of enteric secretomotor neurons results in the
Release of Ach from mucosal neurons and in the induction of active Cl- secretion
131
Example of ENDOCRINE SYSTEM
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
Example of PARACRINE REGULATION
Immune cells in the lamina propria
133
Product of Macrophages
Prostaglandins
| 02 Radicals
134
Product of Mast Cells
Histamine
135
Product of Neutrophils
Eicosanoids
| Platelet-activing factor
136
Product of Fibroblasts
Eicosanoids
| Bradykinin
137
Secretagogues can be classified by their __________ and by the _________
Type
Intracellular second-messenger system that they stimulate
138
Peptide that is produced and excreted by bacteria that can produce effects independently of the bacteria
Bacterial exotoxin
139
An exotoxin that induces changes in intestinal fluid and electrolyte movement
Enterotoxin
140
Explain mechanism of E. Coli HEAT-LABILE toxin
Apical membrane receptors ---> Internalized ---> Activates BASOLATERAL Adenylyl Cyclase ---> Increase cAMP ---> Activates Protein Kinase A
* VIP also acts by this route
141
Explain mechanism of E. Coli HEAT-STABLE toxin
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
How do secretogogues increase Ca2+
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
All three second messengers
Increase Anion Secretion
Inhibit NaCl Absorption
* cGMP's ability to stimulate Cl- secretion is somewhat LESS (+)
144
Mineralocorticoids, Glucocorticoids and Somatostatin are ________
Absorptagogues
145
Primary hormones that enhance intestinal fluid and electrolyte absorption
Corticosteroids
146
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
Mineralocorticoids (e.g., Aldosterone)
* induces both apical membrane N+ channels and basolateral Na-K pumps
147
These stimulate electroneural NaCl absorption throughout the large and small intestine without any effect on either K+ secretion or electrogenic Na+ absorption
Glucocorticoids
* both corticosteroids act at least in part by GENOMIC MECHANISMS
148
Somatostatin as an absortagogue
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)
