Small Intestine

Front 1

Functions of the small intestine

Back 1

secretion of water and electrolytes
2-3 liters of fluid to maintain the fluidity of the chyme
part of the immune response to "flush" infectioous or noxious agents
delivery of IgA's
Mixing and propulsion
secretion of hormones
digestion and absorption
"brush border" enzymes
carrier proteins
Participation in immune response
antigen-antibod interactions
cytokines,, PGs

Front 2

Mucosal Architecture of the Small Intestine

Back 2

Tight Junctoins
Permeable to water and solutes less then 300 MW
crypts more permeable than villi
permeabilitity decreases moving distally - higher in the deodenum then jejunum

Front 3

Mucosal Architecture of the Small Intestine

Back 3

Mucosal Lumenal Surface Area

increased by spiral and circular folds in the mucosa, mucosal villi (not present in the colon), microvilli on mucosal epithelial cells

high surface area for absorptive and secretory functions

Front 4

components of the villus epithelium

Back 4

enterocytes
endocrine cells
goblet cells
interaepithelia lymphocytes

Front 5

Components of the Lamina Propria

Back 5

blood vessels
lymph vessels
nerve fibers
smooth muscle
immune cells

Front 6

components of the crypt epithelium

Back 6

undifferential cells
goblet cells
endocrine/paracrine cells
caveolated cells
paneth cells

Front 7

absorption occurs on

Back 7

the villi

Front 8

secretion occurs from the

Back 8

crypts

Front 9

Mucosal growth and adaption

Back 9

high cellular turnovre rate
balance between cell production and cell loss exists

Front 10

direct effects of food in the GI tract

Back 10

increased local nutrition leads to growth of the mucosa

Front 11

indirect effects of food in the GI tract

Back 11

gastrin and enteroglucagons - trophic effects that lead to paracrine and endocrine effects which cause the growth of mucosa

Front 12

secretions b the small intestine

Back 12

mucus - goblet cells, brunner's glands (duodenum) = physical stimuli (ENS, short loop reflex) and PNS stimulation

sloughed mucosa

Water and electrolytes
2-3 L per day
cryyte cells secrete
villus cells absorb

Front 13

Causes of Net Fluid Secretion

Back 13

hyperosmolality of chyme
secretory filtratoin
active anion secretion coupled with inhibition of neutral NaCl absorption

Front 14

Laxative

Back 14

increases water content of stools

Front 15

Secretory Filtration

Back 15

hydrostatic pressure gradient can be increased by hepatic portal hypertension and plasma dilution

Front 16

physiological control of the absorption and secretion of water and NaCl

Back 16

neural control
endocrine/paracrine control
muscosal immune system control - responsible for global regulation in response to a meal, also, permit local changes in luminal fluidity in response to cues provided by physicochemical status of the luminal contents

Front 17

physiological control of the absorption and secretion of water and NaCl

Neural Control

Back 17

ENS

via short and long loop reflexes the ENS integrates local and systemic inputs to coordinate intestinal ion transport with motor function (increasing or decreasing the residence time of the luminal contents in a given intestinal segment to increase or decrease the net flux of a substance across the epithelium

stimulators of net secretion (ACh, serotonin, VIP)

stimulators of net absorption (NE, NPY, SRIF)

PNS neural input to the ENS (stim net secretion)

SNS neural input to the ENS (stim net absorption)

Front 18

physiological control of the absorption and secretion of water and NaCl

Endocrine/Paracrine

Back 18

GI Hormones - stimulators of net secretion (serotonin, gastrin, secretin), stimulators of net absorption (SS)

Other Hormones - stimulators of net absoprtion (Epi, corticosteroids, angiotensin, and aldosterone (in the colon only)

Paracrine substances - stimulators of net secretoin (VIP, PGEs, His, and bile acids in the colon under pathological conditions)

Front 19

physiological control of the absorption and secretion of water and NaCl

Mucosal immune system control

Back 19

mast cells release stimulators of net secretion (His PGs, Serotonin, Leukotrienes)

directly activate receptors on enterocytes to stimulate net secretion or indirectly stimulate net secretion by action on receptors on ENS neurons to influence motor activity

Front 20

Pathogens that cause net secretion

Back 20

vibrio cholera toxin
escherichia coli entertoxin
clostridium difficle toxin (all stimulate Cl- secretion by crypt cells and all inhibit electroneutral NaCl absoprtion by cells on the villi)

Increased Net Fluid Secretion

Front 21

Motility of the Small Intestine

Back 21

coordinated contractions facilitate digestion and absorption by: mixing chyme with digestive secretions, exposing the lumenal contents to mucosal surface for digestion and absoprtion, moving lumenal contents towards the colon

Front 22

interdigestive period pattern of motility

Back 22

MMC

Front 23

digestive period pattern of motility

Back 23

rhythmic segmenting "ring" contractions (i.e. mixing contractions), peristaltic "ring" contractions that progress down the length of the intestin, "sleave" contractions (shortening of the intestine), contractions of the muscularis mucosae (cause folding of the muscous), contractions of the villi (shorten the villi, promote lymph flow)

Front 24

Movement of intralumenal contents

Back 24

conduit and pump are the same structure, secretion and absoprtoin both occur along the length (consequently, the movement of chyme is complex, in general aboral movement at 1-4 cm/min, more rapid in the duodenum than ileum)

Front 25

intestinal absorptive pathways

Back 25

epithelial barriers to absoprtion

Extrinsic barriers
secretory IgA
mucus
unstirred fluid layer (300-899 nm thick)

intrinsic barriers
apical (brush border)
cytosol
basolateral membrane
interstitial space
basement membrane
endothelial cell or lacteal

Front 26

mechanism of absorption

Back 26

diffusion - simple or facilitated

active transport - primary, secondary (electrolyte - coupled), tertiat (electrolyte-coupled), endo/exocytosisis

Front 27

Sources of protein in the small intestine

Back 27

exogenous (diet) protein
min daily requirement: 0.4 - 0.6 g/kg/day
not all dietary protein is highly digestable (plant proteins, high proline content proteins, cooking denatures proteins making them more digestable)
RDA = 0.8 g/kg/day

Nine "essential" amino acids must be obtained from the diet
val, leu, isoleu, phe, try, thr, met, lys, his
a single vegetable source does not provide a complete set of essential amino acids

Front 28

Sources of protein in the small intestine

Back 28

endogenous protein (approx. 35 g/d)
secretions from salivary glands, stomach, intestine, bilary tract, and pancrease make up a significant portion of the total protein presented to the small intestine (enzymes, glycoproteins, desquamated cells, bilary proteins, IgAs)
some proteins (intrinsic factor secreted by parietal cells) escape luminal digestion

Front 29

Entry of protein digestion products into the enterocyte across the brush bored membrane of polarized intestinal epithelial cells

Back 29

the enterocyte is equipped with transport systems at the two poles of its plasma membrane
the brush border and basolateral membranes exhibit different characteristics (enable cell to perform vectorial transporrt)
most of the transport systems are active and able to mediate uphill transport of substrate)

the brush border and basolatedal membranes are in contact with fluids of vasly different chemical composition (luminal fluid at the brush border membrane, ECF at the basolateral membrane)

Front 30

The driving forces of active trasport in the brush border and basolateral membrane comes from

Back 30

transmembrane ion gradients and membrane potenial

Front 31

exit of protein digestion products across the basolateral membrane

Back 31

there are at least 6 amino acid transport systems in the basolateral membrane

Na+ dependent pathways play a role in supplying the enterocyte with amino acids for cellular nutrition during period between meals

Na+ independent pathways are responsible for transport of amino acids from the cell into the blood (consequently Na+-dependent pathways participate in the overall process of thranscellular absorption og amino acids from the intestinal lumen)

Front 32

Nutritional, clinical, and pharmacological relevance of intestinal peptide transport

Back 32

absorption in the form of peptides rather than free amino acid appears to have nutrtional advantaves (mixtures of a.a. are nutritionally inferior to mixtures of small peptides of comparable a.a. composition)

Reasons include
1. faster absorption of aa's in the form of peptides
2. more even appearance of aa's in blood after absorption from peptide mixtures
3. a voidance of comopstion during transporting aa's and di and tri peptides rathen than single aa
4. conservation fo metabolic energyin transporting aa's di and tri peptides, rather than as single aa's
5. relative resistance of peptide transport compared with aa transport to numerous adverse conditions (e.g. starvatoin, protein-calorie malnutrition, vitamin deficiency, and intestinal disease)

Front 33

Nutritional, clinical, and pharmacological relevance of intestinal peptide transport

clinical implications

Back 33

enteral nutritional support in hospitalizated patients
some commerically available formulae contain amino nitrogen in the elementary form, namely, free amino acids

originially secreted on the assumption that protein digestion products are primarily absorbed as free aa's

enteral diets based on free aa's are hyperosmolar and may be contributing factor in commonly encountered diarrheal complicatoins associated with hyperosmolar forulars

amino acid-based enteral solutions generally lack tyr,glu, and cys, becaue tyr is insoluble, and glu and cys are unstable

enteral diets consisting of small peptides, instead of free aa's may have a greater clinical advantage and nutritional efficacy

Front 34

Nutritional, clinical, and pharmacological relevance of intestinal peptide transport

pharmacological implications

Back 34

absoprtion of orally active beta-lactam antibiotics

aminocephalosporins and aminopenicillins are structurally similar to tripeptides - these are transported across the brush border membrane by the peptide transport system, beta-lactam antibiotics are resistant to intacellularal protease and appear intact in the blood in pharmacologically active forms

other drugs appear to be absorbed, at keast in part, bia the peptide transport system (captopril, bestatin, renin inhibitors)

Front 35

Absorption of intact proteins and peptides

paracellular route

Back 35

the paracellular route through the tight junctions between epithelial cells may be significant for absoption of small molecules across the gi epithelium

"solvent drage"

alterations in tight junction permability - high luminal [glucose] increases permeability such that some small molecules can pass, cytokines from MIS alter the tight junctions

Front 36

Absorption of intact proteins and peptides


intestinal closure

Back 36

neonates can absorb a considerable amount of intact protein across their intestines

this ability begins to less just before birth in full term infants

closure in ont abrupt but can toake up to 140 days after birth

Front 37

Dietary carbs

Back 37

polysaccharides (starch, glycogen)
disaccharides (sucrose, lactose, maltose)
monosaccharides (glucose, fructose)
unavailable carbs

Front 38

Unavailable carbs

Back 38

indigestibile oligosacchardies (raffinose, stachyose)

dietary fiber from fruits, vegetables, cereals, and seeds

unabsorbable monosaccharides (sorbital)

Front 39

only monosaccharides are absorbed

Back 39

polysaccharides (starch) and disaccharides (sucrose) must be digested to yield monosaccharides)

Front 40

carbohydrate intolerance: lactase deficiency

Back 40

unabsorbed disaccharide accumulated in bowl, this increases osmolarity retains or draws water into lumen

metabolism of lactose by bacterial in terminal

this further increases osmolarity, increases flatus, increase H2 and Co2, causing osmotic diarrhea

Front 41

dietary fiber

Back 41

carb components of plant cell walls

undigested by endogenous secretions of the human digestive tract

usually contain beta 14 linkages or other undigestable componentes

Front 42

dietary fiber polysaccharides

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cellulose
hemicullulose
pectins
mucilages
gums

Front 43

dietary fiber non-polysaccharides

Back 43

lingins
saponins
phylates
lipids
silica proteins
ions

Front 44

dietary fibers

Back 44

binds water, increases mass of stool, increases motility

can adsorb certain miners (Ca, Fe, Mg, Zn)

can adsorb organic molecules (bile salts, lipids, drugs)

Front 45

absoprtion of water solube vitamins

Back 45

the majority of all water-soluble vitamines are absorbed from the jejunum and ileum

a variety of mechanisms are involved

some dietar forms of vitamins must first undergo some digestion prior to absoptions

Front 46

Niacin

dietary form

Back 46

nicotinamide nucleotides

Front 47

nicain

Back 47

in the forms, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), its functions in the body as a coenzyme

hydrogen acceptors, which combine with hydrogen atoms as they are removed from food substrates b man different types of dehydrogenase

tryptophan is converted in limited quantities to niacin

Front 48

niacin defciency

Pellagra

Back 48

decreased dehydrogenation

decreased oxidatoin of hydrogen

decreased delivery of energy from foodstuffs to functioning elements of cell

GI symptoms - irritation and inflammation of mucous membranes (sore swollen tongue, gastritis, diarrhea)

Neurological disturbances - dementia, psychosis, depression, apathy

Skin - dermititis (photosensitivity)

Front 49

Riboflavin

dietary forms

Back 49

flavin mononucleotide (FMN)

flavin adenine dinucleotide (FAD)

absorbed by secondary active transport

Front 50

Riboflavin (Vit B2)

Back 50

hydrogen carriers in several important oxidative systems of the body

deficiency:
relatively rare in humans due to prevalence in diet
fine, scaly dermatitis at angles of the nares and mouth
kerititis of the cornea, with invasion of the cornea by small blood vessel

frequently occurs in association with lack of thiamines and/or niacin

deficiency syndromes including pellagra, beriberi, sprue, and kwashiorkor, are probably due to a combined insufficien of several of these vitamins and also proteins

Front 51

folic acid

Back 51

dietary folic acid= pterolypolyglutamate

only pterolypolyglutamate folate (free folate) transported (facilitated diffusion or tertiary active transport)

Front 52

folic acid

Back 52

acts as a carrier of hydroxymethyl and formyl groups
syn of purines and thymine are required for DNA sun (required for growth, maturation of RBCs)

deficieny:
megaloblastic anemia, diarrhea, weight loss, glossitis

requirement increases during pregananc and lactation (neural tube defects)

Front 53

Cobalamin (essential for DNA syn)

Back 53

found in mammalian tissues

vit B12 (cyanocobalamin)
artifact of the isolation procedure, stable, shares the same transport mech

is produced by bacteria and protozoa associated with foods (meat, fish, milk, eggs, not on fruit, veggies, or grains)

Front 54

cobalamin

Back 54

dietary cobalamin is bound to dietary protein

in the stomach:
HCl in the stomach frees cobalamin from dietary proteins, haptocrrin (Hc) a protein saliva and gastric secretions, binds to cobalamin (Hc has higher affinity for cobalamin than intrinsic factor (IF); Hc blocks the binding of IF to cobalamin)

In the duodenum:
Hc is digested away from cobalamin by pancreatic enzymes (allows the IF to bind with cobalamin

In the terminal ileum:
the cobalamin-IF complex binds to receptors on enterocytes and is taken up by REM endocytosis, cobalamin is removed from the IF and exits the basolateral membrane bound to transcobalamin II (TCII)

Front 55

cobalamin

Back 55

hydrogen receptor coenzyme for reducing ribonucleotides to deoxyribonucleotides (promotes growth and RBC maturation)

deficiency:
failure of RBCs to mature properly; rapidly destroed
demylination of large nerve fibers of the spinal cord (psoterior columns espically, lateral columns occasionally) loss of peripheral sensation and paralysis

Front 56

7 possible causes of cobalamin deficienc

Back 56

1. dietary cobalamin deficiancy (vegetarian or vegan diet)

2. depressed IF secretion
(gastrectomy, pernicious anemia)

3. Gastrinoma (Zollinger - Ellision Syndrome)
(excessive HCl secretion impairs pancreatic proteases)

4. Pancreatic insufficieny
(insufficent pancreactic proteases)

5. interference with IF_Cbl complex binding with ileal receptors
(bacterial overgrowth of terminal ileum)

6. decreased ileal receptor numbers
(ileal resection, ileal disease)

7.Transcobalamin II deficiency
(defective TCII dyn, defective transcytosis cholchicine therapy)

Front 57

Water absorption in the small intestine

Back 57

approx 80% of the water entering the small intestine is absorbed by the small intestine (only 1.5 - 2 L passed on to the large intestine)

max rate = approx. 15 L/day

Passive; coupled to transepithelial movement of solute, water is absorbed primarily via the paracellular route: "tight junction" permeability is high in the duodenum and decreased over the length of the small intesting, active transport of solute across epithelial establishes an osmotic gradient

Front 58

Na absorption in the small intesting

4 mechanism

Back 58

1. non-nutrient dependent Na+/H+ exchange (proximal small intestine)

2. solute-dependent Na+ transport (throughout the small intestine)

3. coupled electroneutral Na+-Cl- transport (distal small intestine)

4. connective Na+ movement (bulk flow) - throughout the small intestine