Gastrointestinal Physiology
AnS 536
Spring 2014
Amino Acid Digestion in Infants
First 24 hours post parturition
Ability to absorb intact proteins as
immunoglobulins via clostrum
More important in certain species due to lack of
placental transfer (i.e. cattle, pigs, horses, goats,
sheep)
After 24 hrs ability to absorb intact proteins
drastically reduces
Inability to cross the plasma barrier of the
intestinal lumen
Proteins (milk) broken down into amino acids
Amino Acid Digestion in Infants
Mechanisms for protein digestion
Different in neonate vs adult
Brush border peptidases are present in
neonatal mucosa
Expression does not increase at weaning
Amino acid transporters are functional at birth
but there may be quantitative changes as the
animal matures
Sugar Digestion and Transport in
Infants
Digestion of sugars is different in the
neonate vs the adult
Dependent upon sources of sugar and CHO’s
Neonates: Lactose is primary sugar
Adults: Starches and sucrose
Sugars must be broken down into more
absorbable form
Brush border disaccharidases are essential
Lactase hydrolyzes lactose into glucose and
galactose
Monosaccharides can be absorbed by intestines
Sugar Digestion and Transport in
Infants
Post parturition
Lactase concentrations in gut lumen are very high
Begin to decline until weaning
Weaning
Lactase decreases
Sucrase and maltase increase
Factors contributing to disaccharidase
transition
Dietary intake
Postnatal rise in glucocorticoid secretion modulate
expression of dissacharidase genes
Sugar Digestion and Transport in
Infants
 Glucose
Transported from the lumen by the sodium-dependent
hexose transporter
Expression of transporter does not change with age
(Exception - ruminants)
 Ruminants
Dramatic ↓ in glucose transporter GLUT-1 during first
few weeks after birth
Very low levels after weaning
Fructose transport is also low during suckling
 Rises after weaning
Sugar Digestion and Transport in
Infants
 Sorbitol is absorbed by passive diffusion
 Glucose is actively transported
 Fructose transport
Partially active and carrier mediated
Does not compete for the glucose-galactose system
Rate of intestinal absorption is intermediate to glucose
and galactose, but is utilized more rapidly in the tissues
Absorption is enhanced by the presence of glucose
 A diet high in fructose
Shift in site of lipid synthesis
 Adipose tissue to liver
Sugar Digestion in Infants
Sorbitol
Rate of intestinal absorption is 1/3 of that of
glucose
May be due to its laxative effect in calves
It is metabolized in single pass through the liver
Very low levels are found in blood or urine
Fatty Acid (FA) Transport in Infants
 Fatty acids are contained in:
Triacylglycerols
Phospholipids
Cholesterol esters
 Fat digestion in the neonate is limited initially
Pancreatic secretory function and bile salt metabolism need
to mature
 Milk
99% of FAs in the form of triacylglycerols
Fat is emulsified in the stomach via pre-duodenal lipase
Pancreatic lipase is present in low concentrations at birth
 Little impact on fat breakdown until first year of life
Fatty Acid (FA) Transport in Infants
 Fat breakdown
Stomach motility and lipase facilitate breakdown of fat into
smaller globules
Globules have polar, hydrophilic surfaces that undergo
absorption in the small intestines
Brush border of small intestines absorbs free fatty acid
acylglycerols into the mucosal cell
FA bind to FA-binding protein in the endoplasmic reticulum
Triacylglycerols are resynthesized into chylomicrons
Chylomicrons are released into circulation and metabolized
by the liver
Acid Production in the Stomach
Capacity to secrete gastric juices remains
low at birth but increases significantly
Newborn (15 min) stomach pH: 5.4
Newborn (1 hr) stomach pH: 3.1
Gastric juice production follows colostrum
intake and immunoglobulin absorption
Endogenous hormones stimulate postnatal
adaptation
Gastrin
Gastric mucosal growth and parietal cell proliferation
and differentiation increases
Immunoglobulin Absorption
24 hr period of time for attainment of passive
immunity in livestock
Proteolytic activity of the digestive tract is low
in newborn animals
Further inhibited by trypsin inhibitors in colostrum
Nutrients are able to pass the stomach
without degradation to the small intestine
where absorption occurs
Neonatal Immunity
 Human placenta transports IgG from maternal to
fetal circulation
Babies born with IgG concentration approximately
89% of adult values
 No transport of immunoglobulins across
placenta in farm animals
Offspring born with essentially no circulating IgG
Colostrum provides IgG after birth
Classifications of Mammals Based
on Method for Obtaining Passive
Immunity
•
GROUP I – Primates, Rabbits
•
•
•
GROUP II – Cats, Dogs, Rodents
•
•
•
Extensive transplacental transport of IgG
Limited or no postnatal absorption across small intestinal
epithelium
Extensive transplacental transport of IgG
Some postnatal transport across small intestinal epithelium
GROUP III – Cattle, Sheep, Horses, Pigs
•
•
No transplacental transport of IgG
Extensive postnatal transport across small intestinal epithelium
Selective Transfer of IgG
 Occurs in rats through binding of IgG to FC
receptors in the small intestine
 Time dependent
Non-specific absorption after birth
By 3 d of age, IgG absorption favored
By 7 d of age, IgG absorption selection 20X greater
At 21 d of age, no intact proteins absorbed into
circulation
Non-selective Transfer of IgG
 Occurs in calves and sheep
IgG, IgM, and IgA absorbed in proportion to amounts
in colostrum
 Pigs and foals selectively absorb IgG compared
to other macromolecules
IgA and IgM found on enterocyte surface but not
inside the cell
 Absorption rate decreases with increasing age
Mean time to closure approximately 21 to 26 h of age
Absorption of Colostrum
 Absorption in duodenum regulated by Fc
receptors
Minimal
 Absorption in jejunum and ileum non-specific
Accounts for most of Ig absorption
Absorb anything presented to surface
 Ig’s, bacteria, viruses
 Cells nearest tips have far more absorptive
capability than those nearest crypts
Absorptive capability takes 3-4 days of cellular
differentiation
Absorptive Mechanism
Pinocytosis
Absorbed via intermicrovillous spaces
Absorption permitted by lack of terminal web in
microvilli
Vacuole forms around absorbed material
Vacuole expands as more material absorbed
Vacuole fills cell
Nucleus pushed down to basolateral membrane
Absorptive Mechanism
Filled vacuole pinches off at luminal end
Nucleus and vacuole change places
Vacuole merges with basolateral
membrane
Enhanced by large intercellular spaces in
neonatal intestine
Material in vacuole is “purged” into
intercellular spaces
After Absorption
 Immunoglobulins are absorbed unchanged and
enter the lymphatics
Lymphatics highly fenestrated immediately after birth
Enter circulation via thoracic duct
In circulation, IgG is distributed equally between
extra- and intravascular space
Equilibrium reached in 51 h
 IgG can be secreted back into the intestinal
lumen through the duodenal crypt cells
Efficiency of Ig absorption
40
35
30
25
20
15
10
5
0
0
4
8
12
16
20
24
Time (hours) relative to birth
Closure
Even after closure occurs, cells continue
to take up colostral material into vacuoles
Completed vacuoles do not exchange
places with nucleus or other cellular
organelles
Cell migrates to tips of villi and are
sloughed off and excreted
Factors Affecting IgG Absorption
Rate of IgG absorption increases with
increasing amount of colostrum fed
Apparent efficiency of absorption (AEA)
decreases with increasing mass of
antibody in colostrum
AEA is increased at higher concentrations
when mass is constant
Serum IgG (g/L) = IgG consumed x AEA (%) / serum volume (L)
AEA (%) = serum IgG (g/L) x serum volume (L) / igG inges
Failure of Passive Transfer (FPT)
Low IgG levels greatly increase risk for
death and disease
40% of calves classified as FPT (<10 g
IgG/L)
Colostrum-deprived calves 50-74 times more
likely to die before 3 weeks of age
FPT calves are twice as likely to get sick as
non-FPT calves
NAHMS estimates suggest 22% of all
calf deaths could be prevented by better
colostrum management
Intestinal Closure
 Related to energy availability and intestinal
maturation
Closure occurs at about 21 hours
 Appears to be later if calf not fed
 Crypt cell mitosis rate is low in the fetus, and
more rapid at 1 d of age compared to 3 wk of
age
Migration from crypt to villous tip occurs in fetus
takes 5-7 days
Migration from crypt to villous tip occurs after birth
takes 72 h
“Closure” of Small Intestine
Uptake continues as long as vacuolization
is present
Vacuolated enterocytes disappear
following definite patterns
Proximal segments of small intestine lose ability
long before distal portions
“Closure” of Small Intestine
Hypotheses about closure as a function of
increasing digestive capability
Closure in ungulates independent of gastric and
pancreatic development
In pigs, closure is diet-induced
Colostrum intake accelerates closure in all
ungulates to varying degrees
“Closure” of Small Intestine
Extreme cold, or heat stress decreases
antibody transport
Cold stress increases cortisol which may effect
absorption
Heat stress diminishes absorption and is a
secondary response to hyperadrenalemia
Oxygen availability at birth may directly or
through secondary mechanisms initiate
closure
“Closure” of Small Intestine
Gestational factors may also contribute to
closure
Extended gestation in lambs diminishes
absorption capacity and induces precocious
closure
No such relationship exists in calves
If so, there should be a response to prematurity
Endogenous IgG Production
IgG, IgM, and IgA concentrations begin to
increase within a few days after birth in
colostrum deprived calves
Undetectable in foals until after 7 d of age
Half-life for IgG is antibody dependent
23-39 d in foals
16-50 d in calves
IgG Production by the Calf
(Active Immunity)
Not enough of a response to be effective
in preventing disease
T- and B-cells less functional for first few
months after birth
Poor response to vaccinations for first few
months
Also need to consider that maternal
antibodies (from colostrum) will inhibit
response to calfhood vaccines
Bioactive Peptides and Hormones
Secreted by Newborn Digestive Tract
 Somatostatin
Secreted by D cells within the stomach
Serve to inhibit parietal G and enterochromaffin-like cells
 Gastrin
Secreted by G cells in the stomach when protein products
are present
Function to stimulate parietal, chief, and enterochromaffinlike cells
 Cholecystokinin
Important in regulating pancreatic digestive enzyme
secretion
Pancreatic secretions minimal at time of birth but increase
with age
Bioactive Peptides and Hormones
Secreted by Newborn Digestive Tract
 Insulin
Hormone secreted by pancreas
Aids in glucose regulation
 Motilin
Secreted by endocrine cells of the small intestine mucosa
Aids in regulating the migrating motility complex between
meals
 Secretin
Released from duodenal mucosa primarily in response to
the presence of acid
Inhibits gastric motility and secretion
Stimulates secretion of NaHCO3 from pancreas and liver
Bioactive Peptides and Hormones
Secreted by Newborn Digestive Tract
Epidermal Growth Factor (EGF)
EGF promotes growth of several organs and
epithelia
Receptors present from very early in gestation
Infusion of EGF in fetal sheep increases cortisol
and decreases thyroxine
Fetal rat hepatocytes secrete IGF in response
to EGF
In developing mice, EGF levels appear to be
controlled by thyroid secretions
Bioactive Peptides and Hormones
Secreted by Newborn Digestive Tract
Bombesin
Gastrin releasing hormone
Regulates/stimulates epithelial growth in adult
mammalian GI tract
Regulation often differs in adult and newborn animals
For example, gastrin, CCK, and cerulin have no
activity in suckling rats
Bombesin-like immunoreactivity present in milk
from several species
Indicates potential role for bombesin in developing
gut
Bioactive Peptides and Hormones
Secreted by Newborn Digestive Tract
Vasoactive Intestinal Peptide
Present at birth—VIP may function in utero
Many intestinal peptides have age-specific roles
in intestinal epithelium
VIP continuously expressed during postnatal
development
VIP role in regulation of water and electrolyte
secretion may account for stability in receptor
expression