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chapter 12
Gastrointestinal Digestion and Absorption
immunoreactive trypsin in association with mutational
analysis using dried blood. Treatment of CF patients in-
volves a comprehensive approach. Use of antibiotics and
pancreatic enzyme replacement therapy has been helpful
in treating pulmonary infection and the maldigestion of
food substances, respectively. Recombinant DNase (pul-
mozyme) and N-acetylcysteine have been used in clearing
the airways in patients. A potentially useful agent in clear-
ing airways is
recombinant gelsolin
which degrades actin
present in cell lysates and decreases viscosity. Aerosolized
drugs such as amiloride, an inhibitor of Na+ channel, and
nonhydrolyzable forms of UTP (UTPTS), an activator of
non-CFTR chloride channels, are being tested clinically.
Other experimental molecular strategies for managing
CF include manipulation of endogenous chaperones that
interact with CFTR protein, enhancement of gene tran-
scription by phenylbutyrate and other analogs (used in
Sickle cell anemia, see Chapter 28) and agents that read-
through stop codons in the CFTR messenger RNA (e.g.,
aminoglycosides), protein replacement therapy and gene
therapy. Two major vehicles to introduce normal CF genes
in vivo
are cationic liposomes and replication-deficient
adenoviruses.
Chronic alcoholism
is frequently associated with gen-
eralized malabsorption of major foods and vitamins be-
cause of liver and pancreatic involvement and mucosal
dysfunction.
12.4 Absorption of Water and Electrolytes
Fluid turnover of about 9 L occurs daily in the GI tract.
Ingested water contributes about 2 L, and the remainder
arises from secretions of the GI tract mucosa and asso-
ciated glands. Nearly all of this water is reabsorbed, and
about 200 mL (2%) or less is excreted (Table 12-8). If
the amount of water excreted in feces exceeds 500 mL,
diarrhea results. Similarly, only 2% of Na+ and 10% of
K+ in gastrointestinal fluids appear in the feces. Most
absorption of fluid and electrolytes occurs in the small
intestine.
The gastric mucosa is relatively impermeable to wa-
ter, but the small intestine is highly permeable, and water
transport occurs in both directions depending on osmotic
gradients. The osmolality of the duodenal contents can be
low or high, depending on the food ingested. However, in
the jejunum, the luminal fluid becomes isotonic and re-
mains so throughout the rest of the small intestine. Water
absorption is a passive process and is coupled to the trans-
port of organic solutes and electrolytes. The simultaneous
presence of glucose and Na+ facilitates the absorption of
all three. In the treatment of diarrhea, oral administration
TABLE 12-8
Daily Turnover o f Water in the GI Tract
Source of Fluids
Quantity
(L/d)
Composition
Input
Diet
2.0
Variable
Saliva
1.5
Hypotonic, alkaline
Gastric juice
2.5
Isotonic, acid
Bile
0.5
Isotonic, alkaline
Pancreatic juice
1.5
Isotonic, alkaline
Intestinal juice
1 . 0
Isotonic, neutral
Total
9.0
Reabsorption
Jejunum
5.5
Ileum
2.0
Colon
1.3
Total
8.8
Lost in the stool
(9.0-8.8) =
0.2
of solutions containing glucose and NaCl replaces fluids
and electrolyte.
Na+ is also absorbed separately from organic solutes
through two coupled transport systems, of which one ab-
sorbs Na+ in exchange for H+, while the other absorbs Cl-
in exchange for HCO. In the lumen, H+ and HCOj" com-
bine to give rise to CO
2
and H
2
O, which enter the mucosal
cell or pass through to the plasma. The Na+ absorbed is
pumped out by Na+, K+-ATPase in the basolateral mem-
brane. Cl- follows Na+ passively, with transfer of NaCl
to plasma.
In the colon Na+, Cl- , and water are efficiently
absorbed. Na+ absorption is regulated by aldosterone
(Chapter 32). K+ is secreted into the lumen as a com-
ponent of mucus but is reabsorbed by passive diffusion.
The amount of K+ in the feces is usually far below the
daily intake; however, in chronic diarrhea the loss of ileal
and colonic fluids can cause negative K+ balance.
Disorders of Fluid and Electrolyte Absorption
If the intestinal contents become hyperosmolar, water en-
ters the lumen to produce iso-osmolarity, and fluid and
electrolyte loss occur. This condition is seen in lactose
intolerance, ingestion of nonabsorbable laxatives such as
magnesium salts, and ingestion of sugars such as lactu-
lose. Bile acids inhibit the absorption of Na+ in the colon.
Under normal circumstances, bile acids do not reach the
