38
Nutrient absorption Owen McGuinness Adapted from Patrick Tso and Genie Moore

owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

  • Upload
    others

  • View
    2

  • Download
    0

Embed Size (px)

Citation preview

Page 1: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

Nutrient absorption

Owen McGuinness

Adapted from Patrick Tso and Genie Moore

Page 2: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

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

Page 3: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,
Page 4: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,
Page 5: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

Intestinal Mucosa

Page 6: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

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

Page 7: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,
Page 8: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

FAT (TG)

PROTEIN

CHO

FA, MG FA,MG,

BILE MICELLE

INTRALUMINAL INTESTINAL REMOVAL

ORAL,GASTRIC,

PANCREATIC

BILIARY SURFACE CELLULAR

FA

TG

PHASE OF DIGESTION AND ABSORPTION

CHYLO-MICRONS LY

MPH

SMALLPEPTIDES

AMINOACIDS

AAs

AAs

CA

PILL

AR

IES

OLIGO-AND DI-

SACCHARIDES

MONO-SACCHA-

RIDES

Page 9: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,
Page 10: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,
Page 11: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

CholesterolesterLipase(nonspecific lipase)

Page 12: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,
Page 13: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

Bile salts12 g/L

Phospholipids5 g/L

Cholesterol1 g/L

Protein2 g/L

Electrolytes9 g/L

Bilirubin0.2 g/L

Bile composition

Page 14: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,
Page 15: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

• 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

Glycocholic acid

Page 16: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

Storage and release of bile

Page 17: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

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

Page 18: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,
Page 19: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

Bile salts enhance water solubility of fats derived from the diet

Bile salt conc., mM0 2 4 6 8 10 12 14 16

Solu

bilit

y, m

M

02468

101214

2-Monoglyceride

Fatty acid

DiglycerideTriglyceride

CMC

Page 20: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,
Page 21: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

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

Page 22: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

Bile salt and colipase effects on pancreatic lipase activity

Bile salts inhibit lipase activity unless colipase is present

Time

Fatty

aci

d re

leas

ed Bilesalts

added

Colipaseadded

Page 23: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

Diameter:TG droplet25,000 Å;Micelle 30-100 Å

Page 24: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

Last 1/3 of the ileum:Apical bile salt transporter(active co‐transport withNa+)

Page 25: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,
Page 26: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

Chylomicrons

• Apolipoprotein (APO‐B48)• Triglyceride• Cholesterol ester• 75 to 200 nm in diameter (VLDL 30‐80 nm)

Page 27: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

Chylomicrons leave the enterocyte by exocytosis (reverse pinocytosis)

Page 28: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

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)

Page 29: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

Lymph Chylomicron Appearance(6 ml of ensure in rats)

Lipids 47:571‐80,2012

Page 30: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

Factors affecting the efficiency of digestion and absorption

• Characteristics of the food• Nutritional status• Previous diet• Developmental changes• Genetic factors• Bowel integrity

Page 31: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

Due to the complex nature of Lipid absorption general defects in 

absorption first appear as defects in lipid absorption

Page 32: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

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

Page 33: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

Fat Absorption by Sucrose Behenate Marker Method

Non‐absorbable Marker

Page 34: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

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. 

Page 35: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

O

O

ORO

RO

RO

OR

OR

OR

OR

RO

Sucrose Polybehenate, a component of olestra used in commercial preparation of snack foods is a safe, non-absorbable marker.

Page 36: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

Fat:Marker in Diet is 3:1

Fat:Marker in Aliquot of Feces is 2:1

1/3 of Fat Absorbed

Page 37: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

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*

Sucrose behenate method was published in 2004.

The sucrose behenate method was applied in cystic fibrosis patients in collaboration with Cincinnati Children’s Hospital. J PediatrGastroenterol Nutr. 2010 April; 50(4): 441–446.

Page 38: owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion – Rate is proportional to concentration gradient – No saturation – Some lipids, water,

QUESTIONS?