small intestine

GASTROINTRESTINAL PHYSIOLOGY II
MOVEMENT OF SMALL and LARGE INTESTINE
DIGESTION AND ABSORPTION OF NUTRIENTS
GASTROINTESTINAL DISORDERS
Jana Jurčovičová
SCHEMATIC REPRESENTATION OF GIT
Lenght of GIT segmets:
duodenum:
26 cm
jejunum and ileum: 260 cm
Jejunum – 40% of small intestine
Ileum - 60% of small intestine
colon :
110cm
MOVEMENTS OF THE SMALL INTESTINE
1.
2.
mixing movements – segmentation contraction
propulsive movements (peristalsis)
spaced intervals ≈ 1 cm
frequency ≈ 12 per minute
contraction are weak after atropin
Peristaltic activity of the small intestine is enhanced by serotonin
Peristaltic rush- at infectious diarrhea, or other irritation a
powerfull rapid peristalsis occurs
EMPTYING OF ILEOCECAL VALVE
Ileocecal valve prevents the backflow of fecal content into small intestine. It
prologs the stay of chyme in the ileum whereby it facilitates absorption.
Ileocecal sphinter is controlled by reflexes from the cecum.
MOVEMENTS OF THE COLON
FUNCTION OF THE COLON:
1)
absorption of water andelectrolytes from the chyme
2)
storage of fecal matter untill it is expelled
MIXING MOVEMENT (very sluggish) - HOUSTRATION movement
Large circular constrictions occurs – 2.5 cm of the circular muscle contracts
- almost occlusion. At the same time longitudinal muscle contract. The
combine contractions cause the unstimulated part of the intestine to bulge
outwards - HOUSTRATION
One wave of haustration lasts about 90 second. Another wave of
haustration occurs after several minutes. Thus water and dissolved
substances are absorbed and about 80 – 100 ml of feces is produced.
TIME IN GIT SEGMENTS
esophagus
10 seconds
stomach
1-3 hours
small intestine
4-6 hours
colon
15-25 hours
PASSAGE OF FOOD THROUGH THE INTESTINE
(is dependent on composition and pH of food)
average 9 h
average 6 h
all components of
food 8 -9-h
average 12 h
up to 72 h
PATHWAYS OF THE PARASYMPATHETIC NEURONAL
MECHANISMS FOR ENHANCING DEFECATION REFLEX
DUODENAL SECRETION
The presence of acid, fat, peptides, hyper / hypo-osmosis, irritating
factors in duodenum activates the release of following intestinal
hormones:
SECRETIN – polypeptide of 27 amino-acids is released in response to
acidic chyme in duodenum. Secretin activates secretion of water and
HCO3- , Na+ by pancreatic ducts and liver bile ducts.
CHOLECYSTOKININ – polypeptide of 33 amino-acids is released in
response to partial protein digestion products and fatty acids in the
chyme in duodenum. It activates gallbladder contractions, and acini in
pancreas to release enzymes.
GASTRIC INHIBITORY POLYPEPTIDE, VASOACTIVE INHIBITORY
POLYPETIDE, SOMATOSTATIN have moderate inhibitory effect on
gastric secretion
SECRETION OF SMALL INTESTINE
BRUNNER´s glands – mucous glands located mainly in duodenum. They
secrete mucus in response to tactile / irritating, vagal, and gastrin stimuli.
Brunner’ glands are inhibited by sympathetic stimulation.
CRYPTS OF LIEBERKŮHN:
Are located on the entire surface of small
intestine.
Mucous goblet cells produce mucus.
Epithelial cells (enterocytes) produce water
and electrolytes – 1800 ml per day
Paneth cells produce α-defensins which bind
to phospholipids of the bacterial membrane
(undergo continual
mitosis)
host defense cells
produce α-defensins
DIGESTION IN THE GASTROINTESTINAL TRACT
The food provided the organism with the necessary energy can be classified
as:
CARBOHYDRATES, PROTEINS and FATS
They cannot be absorbed in they natural form through gastrointestinal
mucosa, they can be used as nutrients after preliminary digestion.
CARBOHYDRATES:
Three major sources of carbohydrates in human diet: sucrose (glucose and
fructose), lactose (glucose and galactose) starches (polysaccharide of
glucose), maltose (disaccharide of glucose)
Other carbohydrates: amylose, glycogen, pectins, dextrins, (cellulose ?)
Digestion in saliva: – alpha-amylase (ptyalin) hydrolyses alpha- glycosidic
bindings. About 30 - 40 % of total starch is digested in saliva.
Digestion in small intestine: pancreatic alpha-amylase - more powerfull than
ptyalin
STARCH – AMYLOPECTIN
1-4 alpha linkage
1
1-6 alpha linkage
1
4
6
1
4
CELLULOSE
STARCH – AMYLOSE
1-4 beta linkage
1-4 alpha linkage
4
1
1
1
4
4
4
1
DIGESTION OF CARBOHYDRATES
enterocytes
glucose 4-epimerase
enterocytes
enterocytes
DIGESTION OF PROTEINS
Proteins are formed from amino acids which are bound together by
peptide linkages.
The digestion occurs by a reverse process, hydrolysis where the
proteolytic enzymes return water to the protein molecules to split them
into peptides and consequently amino acids. The most important enzyme
in the stomach is pepsin. Its optimal pH is 2.0 to 3.0. Pepsin can digest
also collagen, an albuminoid, that is difficult to digested by other
enzymes. Collagen is the constituent of the intercellular connective
tissue of meat, thus to break-down collagen is the first necessary step for
other enzymes to reach the cellular content of fat.
DIGESTION OF PROTEINS
Pepsin digests proteins to about 20%. Most protein digestion occurs in upper small
intestine, in the duodenum and jejunum under the enzymes of pancreatic secretion.
Proteins leave stomach as proteoses, peptons and polypeptides. Enzymes of the
pancreatic fluids break proteins into dipeptides, or larger peptides.
Digestion of di- and higher – peptides occurs in the small intestine by enzymes in
enterocytes that line the villi. These are aminopolypeptidase and dipeptidases
to give rise to dipeptides, tripeptides, and aminoacids. The amino acids are easily
transported through the enterocytes into the blood. If some polypeptide or even
protein enters the circulation it may cause allergic or immunological disturbances.
DIGESTION OF FAT
The prevalent form of fat in the diet are neutral fats called triglycerides
composed of glycerol and three fatty acids. These are major constituent of food of
animal origin. In the diet are also phospholipides, cholesterol, cholesterol esters.
(Cholesterol is a sterol compound which does not contain fatty acids)
Digestion of triglycerides starts in saliva by lipase secreted by Ebner cells, but
pancreatic lipase plays a crucial role.
DIGESTION OF FAT
The crucial step necessary for fat digestion is emulsification. It is achieved under
the influence of bile which is secreted by the liver.
Bile contains bile salts, and phospholipid lecithin.
The polar part of bile salt and lecitin are soluble in water, the remaining non polar part
of the molecules are soluble in fat. In this way the fat soluble portions of the molecule
dissolve in the surface layer of fat globules. At the same time the polar part projecting
outwards is soluble in water. This effect greatly decreases the interfacial tension
between fat and water. Under agitation the fat globules are more fragile and
fragmentable in the small intestine. The total surface area of the fat particles in the
intestine is larger and more accessible to the water soluble enzyme, lipase.
The bile salt micelles transport the digested fat – monoglycerides and fatty acids to
the brush borders of epithelial cells, and the bile is released and reused.
Cholesterol esters and phospholipids are hydrolyzed by enzymes of pancreatic
secretion: cholesterol ester hydrolase, and phospholipase A2.
The bile salt micelles play here the same role as mentioned above. Indeed no
cholesterol can be digested without the function of the micelles.
GASTROINTESTINAL ABSORPTION
Stomach is a very poor absorptive area because of
lack of villus type of absorptive membrane and because
of tight junctions between the epithelial cells. Only
alcohol and some drugs like aspirin can be absorbed in
stomach.
The total quantity of fluid must be absorbed by the
intestinal mucosa. The absorption occurs by:
active transport
diffusion
solvent drag
The amount of ingested fluid during the day is about 1.5
liters, the amount of product of the gastrointestinal
secretions is about 7 liters. The total absorbed fluid is
8 – 9 liters per day.
From the mucosa project many folds called valvulae
conniventes. They increase the surface area of
absorptive mucosa about three-fold. These are
covered villi that increase the area another 10 times.
Each villus is covered by brush border microvilli that
increase the area another 20 times
longitudinal section of
small intestine
LONGITUDINAL SECTION
OF THE VILLUS
CROSS SECTION OF
THE VILLUS
ABSORBTION OF NUTRIENTS
.
SMALL INTESTINE - daily absorption - several hundreds grams of carbohydrates,
100 grams of fat, up to100 grams of aminoacids and ions, and about 8 liters of water.
LARGE INTESTINE - can absorb water, and ions, almost no nutrients.
ABSORPTION OF WATER: diffusion which obeys the law of osmosis.
ABSORPTION OF SODIUM IONS:
Na+-K+ATPase
ABSORPTION OF VITAMINES AND MINERALS
VITAMINS
are absorbed in the upper jejunum. Water soluble vitamins are absorbed by active
cotransport with Na+. Vitamin B12 is absorbed in ileum bound to intrinsic factor.
Fat soluble vitamis are absorbed together with fat.
CALCIUM
is absorbed mainly in upper jejunum. Calcitriol activates production of Ca++ binding
proteins along with Ca++- H + ATPase
IRON
Is absorbed as Fe2+. Major form in food is Fe3+. Fe3+
Fe2+ in stomach by
ascorbic acid, in intestine epithelial cells by Fe3+ reductase.
luminal
membrane
e
hem
oxygenase
reductase
basolateral
membrane
blood
ABSORBTION OF CARBOHYDRATES
Eighty % of the used carbohydrate calories come from absorbed glucose, which is
a final product of starch digestion. The remaining 20 % come from galactose and
fructose
Galactose is transported by the same mechanisms as glucose. Fructose is
absorbed independently from sodium by facilitated diffusion using GLUT- 5. The
rate of transport is half of glucose or galactose. Much of galactose is converted to
glucose in enterocytes and is further processed as glucose.
ABSORBTION OF PROTEINS
Proteins are absorbed through the membrane enterocytes in form of free
aminoacids by a sodium co-transport mechanisms, similarly to glucose.The sodium
ions move down the electrochemical gradient into the cells pulling the aminoacids
and some peptides with it. Several specific aminoacid transporters have been
characterized in the luminal membrane of intestinal epithelial cells.
There is no absorption of peptides longer than four amino acids. However, there is
abundant absorption of di- and tripeptides in the small intestine. These small
peptides are absorbed into the small intestinal epithelial cell by cotransport with H+
ions via a transporter called PepT1.
Once inside the enterocyte, the vast bulk of absorbed di- and tripeptides are
digested into amino acids by cytoplasmic peptidases and exported from the cell into
blood. Only a very small number of these small peptides enter blood intact.
Absorption of intact proteins occurs only in a few circumstances. In the first place,
very few proteins get through the membrane bound proteases intact. Second,
"normal" enterocytes do not have transporters to carry proteins across the plasma
membrane and they do not permeate tight junctions.
ABSORBTION OF FATS
The end products of fat digestion are
monoglycerides and free fatty acid. In the
form of the bile acid micelles they are brought
to the surface of the microvilli and diffuse
immediately through enterocyte cell. Lipids
enter the enterocytes by concentration gradient
The bile acid micelles are left in the chyme and
are reused. FERRYING OF LIPIDS
FORMATION OF CHYLOMICRONS.
After entering the enterocytes, the lipids are taken up by smooth endoplasmatic
reticulum to form new triglycerides.
They aggregate into globules containing absorbed cholesterol, phospho-lipids in Golgi
complex . These globules are called chylomicrons.
The phospholipids are arranged in the globules with their fatty portion towards the
center, and with their polar portion towards the surface of the globules.
They are release from Golgi apparatus, excreted by cellular exositosis into the space
around the cells. Thereafter they pass into the central lacteal of the villus and are
transported by the lymphatic pump upwards through the thoratic duct to be brought up to
the great vein
Apolipoproteins are structural
components of lipoprotein particles
CHYLOMICRON
STRUCTURE
They function as:
lipid transport proteins
ApoA, ApoB,
ApoC, ApoE
enzyme cofactors
receptor ligand for intetractions in
tissues
(apolipoproteins)
T triacylglycerol)
C (cholesterol)
green
(phospholipids)
GASTROINTESTINAL DISORDERS
SWALLOWING AND ESOPHAGUS
paralysis of the swallowing mechanisms - damaging swallowing centers in brain
stem, paralysis of swallowing muscles (muscle dystrophy myastenia gravis)
achalasia and mega esophagus - the musculature of the lower esophageal
sphinger is spastically contracted (about 1L of food can be held)
STOMACH
gastritis (inflammation) - ulcerative excoriation of the stomach mucosa,
penetration of H+ ions through gastric barrier
achlorhydria - stomach fails to produce HCl, lack of pepsins secretion (insufficient
digestion), lack of intrinsic factor secretion (anemia)
peptic ulcer – insufficient mucus secretion by Brunner’s gland in upper duodenum,
bacterial infection
SMALL INTESTINE
lack of pancreas secretion that occurs when bile duct is blocked by galstones. It
leads to digestion of pancreas by its own enzymes
malabsorption - “sprue” (celiac disesase, gluten enteropathy), tropical sprue
GASTROINTESTINAL DISORDERS
LARGE INTESTINE
constipation – caused by irregular bowel habits through life time inhibition of normal
defecation reflexes, megacolon caused by deficiency of myenteric plexus in sigmoid
colon
diarrhea - enhanced mucose secretion due to infection or other irritation (Cholera
toxin stimulates secretion of crypt of Lieberkůhn; Psychogenic diarrhea – extensive
activation of parasympathetic neurons; Ulcerative colitis – autoimmune inflammation
vomiting
UTILIZATION OF NUTRIENTS FOR ENERGY FORMATION
The energy available in foods has been used by various physiological systems of the
cell: For example muscle activity, secretory activity of glands, maintenance of
membrane potentials by nerve and muscle cells, synthesis of substances, food
absorption etc. Free energy is the amount of energy liberated by complex oxidation
of nutrients.
CARBOHYDRATES
Glucose can be used directly by the cells in the glycolytic pathways to produce energy
in a form of ATP. Excess of glucose can be stored by the liver in a form of glycogen.
If the glucose level in blood falls, liver triggers glycogenolysis to return glucose to the
blood. It is called glucose buffer function of the liver.
LIPIDS
The lipids enter the circulation in a form of chylomicrons composed of triglycerides,
9% of phospholipids, 3 % of cholesterol. The chylomicrons are taken up by
adipose tissue and liver. They are degraded by lipoprotein lipase and the fatty acids
diffuse into the fat cells of adipose tissue and into the liver. The triglycerides are
hydrolyzed into fatty acids and glycerol. Glycerol in form of glycerol 3-phosphate
enters the glycolytic pathways to give energy. Fatty acids are degraded by beta
oxidation into acetyl-coenzyme A. This enters the citric acid cycle in mitochondria to
produce energy .
CHOLESTEROL
Special function among fats has cholesterol. It is a sterol compound the does
not contain any fatty acid, but it shares some characteristics with fat, it is metabolize
similarly to fats. So it is considered from a dietary point of view, a fat.
Cholesterol is absorbed from the gastrointestinal tract - exogenous cholesterol, or
it can be formed in the liver from multiple molecules of coenzyme A.
It is primarily used to built up cell membrane. Other use is to form folic acid in the
liver. Small amount is used for the synthesis of steroid hormones in adrenal cortex
and ovaries.
Atherosclerosis begins with the deposition of cholesterol crystals on the inside
surface of arterial walls. With time the crystals grow larger, plus the surrounding
muscle tissue proliferates, and finally reduce the blood flow.
AMINO ACIDS
Product of protein digestion and absorption are amino acids. After the entry of
amino acids into the cells they almost immediately are used for synthesis of peptides
and proteins under the direction of mRNA. About 3/4 of the body solids are proteins,
e.g. structural proteins, enzymes, hormones, nucleoproteins, proteins for muscle
construction etc.
DIETARY BALANCE
The intake of food must cover the metabolic needs of the organism, yet it should
not be excessive to induce obesity.
The well balanced food must contain appropriate proportion of carbohydrates,
fats, and proteins , plus vitamins, and minerals.
The energy liberated from 1 g of:
carbohydrate is 4.1 calories,
fats is 9.3 calories
proteins is 4.1 calories
Daily requirement : - about 2800 cal that should be covered by 70 grams of
proteins (70 x 4.1), 60 grams of fats (60 x 9.3),and the rest 2800-(287+558) =1955
by carbohydrates = 477 g.
Fats and carbohydrates spare protein. When food is abundant in carbohydrate
and fats, the body energy is derived from these substrates and proteins are spared.
The intake of proteins is necessary to provide the body with amino-acids to built up
its own protein pool. In the protein intake should be a sufficient amount of
essential aminoacids. From 20 amino acids 10 are essential, which are not
synthesized either at all, or in sufficient amount in the body. These are: arginine,
histidine, leucine, isoleucine, lysine, methionine, phenylalanine, threonine
tryptophan, valine
DIETARY BALANCE
Some proteins have inadequate amount of essential amino acids, and
therefore cannot be fully used to form body proteins. These are called
partial proteins, and are derived from vegetables and grain sources.
Proteins derived from meat, fish, and eggs have the same ratio of amino
acids that is needed for the synthesis of proteins in the human body.
A dietary deficiency resulting from nutrition containing only partial proteins
(primarily corn which does not contain tryptophan) gives rise to
kwashiorkor syndrome. It is manifested by growth retardation in children,
lethargy, depressed mentality, and hypo-protein edema.
WHAT ABOUT ALTERNATVE NUTRITION?
(health benefits and risks of plant proteins)
VEGETARIANS – lacto-ovo consume plant food, milk, dairy products, eggs
VEGANS – consume exclusively plant food
REGULATION OF FEEDING, OBESITY AND STARVATION
Hunger is associated with the empty stomach which undergoes rhythmical
contraction – hunger contraction.
Appetite is used in the same sense, but it implies a specific desire for
certain type of food.
Satiety is the opposite of hunger. Satiety results from a filling meal, when
the adipose tissue and glycogen stores are filled.
These feelings are regulated in hypothalamus by ghrelin produced by the
stomach mucosal, leptin produced by adipocytes, insulin produced by
pancreas.
FOOD INTAKE
ENERGY EXPENDITURE
XCVCV
MICE LACKING LEPTIN INHIBITION OF NPY