WATER TRANSPORT AND
DIARRHEA
Anson Lowe
Medicine/Gastroenterology
September 25, 2015
Understand water transport
 Understand the causes of diarrhea
 Understand secretory vs. osmotic diarrhea


Water transport; diarrhea
Grant’s Atlas, 1972
Ingested
Endogenous secretions
Salivary glands
Stomach
Bile
Pancreas
Intestine
Total input
Reabsorbed
Jejunum
Ileum
Colon
2000
7000
1500
2500
500
1500
1000
7000
9000
8800
5500
2000
1300
8800
Balance in stool
*Moore,EW, Physiology of Intestinal Water and Electrolyte Absorption, 1976
200
Black RE, et al., Lancet 375:1969 (2010)
Childhood Deaths

11 million per year
◦ 1 in 5 die before their fifth birthday
70% are secondary to pneumonia, diarrhea,
measles, malaria, and malnutrition
 2 million die of diarrhea diseases, 90% of
whom could have been saved by the
appropriate treatment

Cholera Death Rates
Estimated 1 million cases / year
100,000 - 130,000 deaths / year
Case fatality rates:
South Africa = 0.22%
Other parts of Africa = up to 30%
WHO
Gary Schoolnik
Environmental Degradation Begets Epidemics: Cholera in Bangladesh
Medicine Grand Rounds
November 21, 2007
url: http://lane.stanford.edu/biomedresources/grandrounds/medgrandrounds-2007.html
transepithelial P.D.
mucosal resistance
passive NaCl movement
[Na+] equilibrium conc.
Jejunum
-3mv
low
high
133 mEq/l
ileum
-6mv
med
low
75
Colon
-20mv
high
minimal
30
What is the implication with respect to stool osmolarity?
What is the difference between the nephron and the intestine?
www.med.uiuc.edu
http://en.wikipedia.org/wiki/Thick_ascending_limb_of_loop_of_Henle
Absorption of most solutes from the intestinal
lumen is secondary active transport. The
major driving force is Na+:K+-ATPase.
 Unlike the kidney, the intestine does not
possess a diluting segment. Thus the
intestinal fluid is always isotonic with respect
to plasma.

Stool Osmolarity
In contrast to the kidney, the GI tract cannot
dilute or concentrate its contents
 Stool contents is always isotonic
 Serum osmolarity is tightly regulated at
~290 mosm.


Why do we separate digestion into a
lumenal and mucosal phase?

Why do we separate digestion into a
lumenal and mucosal phase?
◦ Lumenal digestion of a disaccharide would
increase intestinal volume two-fold
Hypertonic Stool
Hypertonic Stool
• High stool osmolarity suggests
a prolonged period of
incubation before processing.
Sleisenger and Fordtran, Gastrointestinal Disease, 5th ed.
Hypotonic Stool
Hypotonic Stool

Suggest the addition of free water to the stool
Osmotic Gap
Osmotic gap = 290mosm - (([Na+] + [K+] ) x 2)
A gap of < 40mosm suggests a secretory diarrhea
How do we absorb water?
How do we absorb water?

Beer = 4 mosm/liter
Proc. Natl. Acad. Sci. USA93:13367-13370 (1996)
SGLT1 and Water Absorption

Co-transport of 2 Na+, 1 glucose, and 264
water molecules
◦ Blocking glucose transport with phlorizin will also
block water transport
SGLT1 and Water Absorption
Also able to transport water in response to an
osmotic gradient
 Produces an osmotic gradient that can be used
by other water channels such as the
aquaporins

WHO Oral Rehydration Solution





[Na+] = 90 mEq/L
[K+] = 20 mEq/L
[Cl-] = 80 mEq/L
Citrate = 30 mEq/L
Glucose = 20 gm/L (111 mM)
Alberts et al, Moleculare Biology of the Cell, 3rd ed.
CFTR
Functions as a chloride channel and also
regulates other transport pathways
 Can mediate water transport

Advantage of CFTR mutations?
Advantage of CFTR mutations?

Knockout CFTR mice have been produced
Advantage of CFTR mutations?

Knockout CFTR mice have been produced
◦ Mice die of intestinal obstruction
Advantage of CFTR mutations?

Knockout CFTR mice have been produced
◦ Mice die of intestinal obstruction

Homozygous mice are resistant to cholera toxin
Advantage of CFTR mutations?

Knockout CFTR mice have been produced
◦ Mice die of intestinal obstruction
Homozygous mice are resistant to cholera toxin
 Heterozygote mice are partially resistant to
cholera toxin

Normal Pancreas, H&E
Univ. of Kansas, Dept. of Pathology
Secretory Diarrheas
E. coli heat stabile enterotoxin
 Cholera
 Staph. Aureus
 B. Cereus
 Vasoactive intestinal peptide (VIPoma)

Secretory Diarrheas
Excess secretion
 Nutrient absorption intact

◦ Therapy?
Secretory Diarrheas
Excess secretion
 Nutrient absorption intact

◦ Oral rehydration formula





[Na+] = 90 mEq/L
[K+] = 20 mEq/L
[Cl-] = 80 mEq/L
Citrate = 30 mEq/L
Glucose = 20 gm/L (111 mM)
Secretory Diarrhea due to a
VIPoma?
(vasoactive intestinal peptide)
Somatostatin
Source:
◦ Neurons of CNS and PNS
◦ Endocrine cells of the pancreas (D cells) and stomach
 Actions in the GI tract
◦ Inhibition of transport
◦ Inhibition of secretion
◦ Splanchnic vasoconstriction

Somatostatin

Clinical Applications
◦ Inhibition of many G-protein mediated processes
 Secretory diarrhea
 Pancreatic secretions
 Gastrointestinal hemorrhage (variceal bleeding)
 induces splanchnic vasoconstriction
Diarrhea-Acid/Base Disorders

What disturbances in acid base balance will be
seen with significant diarrhea?
Diarrhea-Acid/Base Disorders

What disturbances in acid base balance will be
seen with significant diarrhea?
◦ Non-anion gap metabolic acidosis
Anion gap = ([Na] + [K]) - ([Cl] + [HCO3-])
Distal Colon
high resistance, high potential difference,
low permeability to ions
 no nutrient dependent absorption

(e.g. Na+:glucose)

responsive to mineralcorticoids
transepithelial P.D.
mucosal resistance
passive NaCl movement
[Na+] equilibrium conc.
Jejunum
-3mv
low
high
133 mEq/l~
ileum
-6mv
med
low
75
Colon
-20mv
high
minimal
~30
Metabolic Changes with Diarrhea

Hypokalemic, hyperchloremic, non-anion gap
metabolic acidosis
colonic limit is < 5L/d
Stool Characteristics
•
•
•
•
•
consistency of the stool (semi-solid or watery)
stool volume
presence of blood or pus in the stool
nocturnal diarrhea
relationship to meals
Definitions of Diarrhea
Stool consistency
 Stool volume
 Frequency (> 2/day)
 Stool volume > 250 g/day

Gastrointestinal Disease, ed: M.H. Sleisenger and J.S. Fordtran (1989), page 1034
Stool fecal volume > 250 g/day
fecal fat, fecal electrolytes
< 6g fat /day
osmotic gap (? secretory or osmotic)
yes
osmotic
stool pH
laxative screen
no
secretory
VIP
5HIAA
histamine
calcitonin
thyroid function
laxative screen
> 6g fat/day, osmotic
D-xylose test (check mucosal integrity)
normal
CT scan
ERCP
trial of pancreatic enzymes
abnormal
small intestinal biopsy
small intestinal X-ray