Nutrient absorption
Owen McGuinness
Adapted from Patrick Tso and Genie Moore
Average daily intake in the U.S.
• Total energy intake: 2150 kcal
– Protein: 79 g (2/3 animal, 1/3 plant sources)
– CHO: 265 g
– Fat: 81 g
– Alcohol: 8 g (2/3 of a beer)
From NHANES publication 245, July 2002 www.cdc.gov/nchs/data/sr_11
Intestinal Mucosa
Transport across the apical membrane
• Passive diffusion
– Rate is proportional to concentration gradient
– No saturation
– Some lipids, water, high doses of many water soluble vitamins
• Facilitated diffusion
–
–
–
–
Rate exceeds that of passive diffusion
Saturation kinetics observed
No accumulation against a concentration gradient
Fructose, low doses of water soluble vitamins such as folate, C, B12
• Active transport – linked to Na+,K+‐ATPase
– Energy requiring
– Can occur against a concentration gradient
– Glucose, amino acids
PHASE OF DIGESTION AND ABSORPTION
INTRALUMINAL
BILIARY
FA, MG
FA,
MG,
BILE
MICELLE
SMALL
PEPTIDES
PROTEIN
CHO
SURFACE
CELLULAR
FA
CHYLOMICRONS
LYMPH
TG
AAs
AAs
AMINO
ACIDS
OLIGOAND DISACCHARIDES
REMOVAL
MONOSACCHARIDES
CAPILLARIES
FAT (TG)
ORAL,
GASTRIC,
PANCREATIC
INTESTINAL
Cholesterolester
Lipase
(nonspecific
lipase)
Bile composition
Bile salts
12 g/L
Phospholipids
5 g/L
Cholesterol
1 g/L
Protein
2 g/L
Bilirubin
0.2 g/L
Electrolytes
9 g/L
Glycocholic acid
• 98% of bile acids are conjugated with amino acids when secreted
– Conjugation occurs in the liver
– Glycine and taurine are the preferred amino acids in humans – Conjugation increases solubility in aqueous environment
• Cholic acid soluble to 0.28 g/l in water at 15ºC
• Glycocholic acid soluble to 274 g/l
Storage and release of bile
Bile salts
• In gallbladder, concentration is >35 mM
– Spontaneously form micelles with polar portions oriented outward
• Diluted in duodenum to 10‐20 mM
• Critical micellar concentration required for mixed micelle formation with products of fat digestion is approx. 2 mM
Solubility, mM
Bile salts enhance water solubility of fats derived from the diet
14
12
2-Monoglyceride
10
Fatty acid
8
6
4
CMC
Diglyceride
2
Triglyceride
0
0
2
4
6
8
10 12 14 16
Bile salt conc., mM
Bile acids
• Help to emulsify fats, decreasing surface area of lipid droplets
• Lower the pH optimum of pancreatic lipase from neutral to 6
• Improve transport of FA and MAG through unstirred water layer
– Essential for the absorption of the fat soluble vitamins
• Release enterokinase from the brush border (? Role in trypsin activation)
• Result in some cholesterol excretion
Bile salt and colipase effects on pancreatic lipase activity
Fatty acid released
Bile salts inhibit lipase activity unless colipase is present
Bile
salts
added
Colipase
added
Time
Diameter:
TG droplet
25,000 Å;
Micelle 30100 Å
Last 1/3 of the ileum:
Apical bile salt transporter
(active co‐
transport with
Na+)
Chylomicrons
•
•
•
•
Apolipoprotein (APO‐B48)
Triglyceride
Cholesterol ester
75 to 200 nm in diameter (VLDL 30‐80 nm)
Chylomicrons leave the enterocyte by exocytosis (reverse pinocytosis)
Medium chain triglycerides (MCT)
• Fatty acids are 6‐12 carbons long and saturated
– Not common in diet, used in specialized formulas for patients with decreased pancreatic secretion or intestinal surface area
• Digestion and absorption
– Hydrolyzed by lipase more rapidly than LCT – Do not require micelle formation
– MCT small and soluble enough so that some appear to be absorbed intact or as diglycerides
• Enterocyte handling and transport
– Little affinity for FABP
– Little incorporated into chylomicrons
– Transported in portal vein blood (bound to albumin)
Lymph Chylomicron Appearance
(6 ml of ensure in rats)
Lipids 47:571‐80,2012
Factors affecting the efficiency of digestion and absorption
•
•
•
•
•
•
Characteristics of the food
Nutritional status
Previous diet
Developmental changes
Genetic factors
Bowel integrity
Due to the complex nature of Lipid absorption general defects in absorption first appear as defects in lipid absorption
Standard Fat‐Balance Method
• Requires accurate measurement of fat in diet from 2‐3 days
• Requires total stool collection for a period corresponding to the analyzed diet
• Requires analysis of the total stool by homogenization, aliquots, fat measurement
Fat Absorption by Sucrose Behenate Marker Method
Non‐absorbable Marker
The Use of a Non‐absorbable Marker Facilitates Measurement
• Animals receive diet with known concentration of marker for 4 days.
• On days 3 and 4, a fecal sample (1‐2 pellets) is taken.
• The ratio of fatty acids to behenate in the fecal sample is analyzed and absorption calculated. OR
OR
OR
O
OR
RO
RO
O
O
RO
RO
Sucrose Polybehenate, a component of olestra used
in commercial preparation of snack foods is a safe,
non-absorbable marker.
Fat:Marker in Diet is 3:1
Fat:Marker in Aliquot of Feces
is 2:1
1/3 of Fat Absorbed
Sucrose behenate method was published in 2004.
Gastroenterology 127: 139-144,2004
A novel, noninvasive method for the measurement of intestinal fat absorption
Ronald J. Jandacek*, , , James E. Heubi‡ and Patrick Tso*
The sucrose behenate method was applied in cystic fibrosis patients in collaboration with Cincinnati Children’s Hospital. J Pediatr
Gastroenterol Nutr. 2010 April; 50(4): 441–446.
QUESTIONS?