17 Small Bowel Physiology Part 2

Question 1

Nutrient Absorption (p.35-38)

• small intestine
  
  • surface area
  • ideally suited for/
  • nutrient uptake
• what contributes to limits (saturation kinetics).
• The digestive process
  
  • starts with
  • breakdown
  • additional mechanical and chemical fragmentation
  • gastric enzymes
  • bile
  • Protein and carbohydrate digestion

Answer 1

• small intestine
  
  • large surface area due to macro- and microscopic invaginations,
  • ideally suited for absorption.
  • nutrient uptake is very fast.
• what contributes to limits (saturation kinetics).
  
  • The effective mechanical and chemical fragmentation of ingested material
  • the uptake into and transport out of the intestinal epithelium
• The digestive process
  
  • starts with the initial bite.
  • Mastication (i.e. the grinding of the food bolus in the oral cavity) and digestive enzymes within the saliva (amylase) begin the breakdown that continues through the gut lumen.
  • In the stomach, additional mechanical and chemical fragmentation occurs.
  • Among the gastric enzymes are pepsin (protein digestion) and lipase (fat digestion).
  • In the proximal small intestine, bile starts to emulsify fat.
    
    • The smaller droplets with their less hydrophobic outer surface allow more effective lipolysis through the pancreatic enzymes.
  • Protein and carbohydrate digestion continues within the intestinal lumen through many enzymes secreted by the pancreas.

Question 2

Carbohydrate Absorption (p.39-40)

• chemical fragmentation of carbohydrates
• Maltose and disaccharides

Answer 2

• chemical fragmentation of carbohydrates starts in the oral cavity and really speeds up with the addition of pancreatic amylase, generating dextrins and eventually maltose.
• Maltose and disaccharides contained in our diet (e.g., lactose) are broken down by specialized brush border enzymes (disaccharidases), freeing up glucose, fructose and/or galactose (depending on the type of disaccharide) that is then taken up by the enterocytes.

Question 3

Carbohydrate Absorption (p.41-45)

• breakdown of lactose
• lactase expression decreases/
  
  • This is not the case in some/
• sucrase-isomaltase activity

Answer 3

• The brush border of intestinal epithelial cells contains specialized enzymes catalyzing the breakdown of lactose, which cleaves lactose into glucose and galactose.
• lactase expression decreases after weaning, explaining the lactose intolerance as the non-absorbable sugar will enter the colon and contribute to diarrhea and bloating (fermentation through bacteria creates gas).
  
  • This is not the case in some Caucasians who continue to express high lactase levels throughout their adult lives , gained an evolutionary advantage and could be considered the ‘founders’ to one of the more recent mutations that provided its carriers with access to an important nutrient source
• As lactase levels drop, sucrase-isomaltase activity increases

Question 4

Sugar Transporters (p.46-49)

• Once disaccharides are cleaved, the monosaccharides/
• the electrochemical gradient
  
  • favors/
  • provides/
• SGLT1
• At the basolateral site, glucose/
• relevance of these sodium-coupled uptake mechanisms

Answer 4

• Once disaccharides are cleaved, the monosaccharides have to be absorbed, which may take place against a concentration gradient.
• the electrochemical gradient
  
  • favors sodium uptake into the cell.
  • provides the driving force for many transport systems (co-transport).
• SGLT1,
  
  • the glucose 2Na+ coupled glucose transporter,
  • provides the main route for glucose uptake.
• At the basolateral site, glucose follows its own concentration gradient and is transported via facilitated diffusion
• relevance of these sodium-coupled uptake mechanisms.
  
  • glucose uptake drags water into the cell.
  • many transporters indirectly contribute to water absorption.
  • This mechanism provides the basis for the use of glucose in the WHO rehydration solution, given in children with dehydration due to severe diarrheal disease.

Question 5

Sugar Transporters (p.50-52)

• There are other systems that allow carbohydrates to cross the membrane by using/
• GLUT5.
• Implications of increased fructose intake
• glucose transport capacity vs. GLUT5 capacity
• The consequence

Answer 5

• There are other systems that allow carbohydrates to cross the membrane by using carriers that are not coupled with electrolyte transport.
• GLUT5.
  
  • responsible for fructose uptake.
• Implications of increased fructose intake
  
  • obesity,
  • selective malabsorption.
• While glucose transport capacity can increase, the GLUT5 capacity is not as effective and not as effectively regulated.
• The consequence:
  
  • more fructose intake can translate into fructose remaining in the gut lumen, dragging water into the colon, where fermentation will take place
  • contributes to symptoms of bloating, flatulence and/or diarrhea.

Question 6

Protein Absorption (p.53-54+56-58)

• Protein digestion
  
  • starts/
  • chyme
  • peptidases
  • amino acids
    
    • specificity
• glutamine,
  
  • When added to the luminal side of intestinal epithelium/
  • providing the same molecule from the basolateral side/
  • Thus, the gut needs/
  • There are other uptake mechanisms for peptides that couple/

Answer 6

• Protein digestion
  
  • starts in the stomach, where gastric pepsinogen is secreted and activated.
  • As chyme enters the duodenum, pancreatic enzymes are added and cleave the proteins into small peptides.
  • Additional peptidases from the intestine further decrease the size of these molecules down to single amino acids, di- or tripeptides.
  • Amino acids are taken up by specialized transport proteins.
    
    • The specificity is characterized by the physico-chemical properties of amino acids (e.g., neutral, acidic…).
  • these transporters can typically move more than a single type of molecule.
    
    • some of these transporters couple the uptake with sodium influx.
• glutamine,
  
  • When added to the luminal side of intestinal epithelium, it decreases the ‘leakiness’ (just one parameter).
  • providing the same molecule from the basolateral side (~ blood stream), cells do not show the improved function.
  • Thus, the gut needs luminal exposure to certain substances.
  • There are other uptake mechanisms for peptides that couple peptide absorption with proton influx.

Question 7

Fat Absorption (p.59-60+62-66)

• Protein and carbohydrate absorption required/
  
  • the difficulty
  • amphiphatic bile acids
  • micelles
• Once in the cell, the cellular machinery/

Answer 7

• Protein and carbohydrate absorption required the chemical cleavage of molecules through a series of enzymatic reactions.
  
  • the difficulty is to provide a favorable environment of enzymatic digestion in the watery (lipophobic) environment of the intestinal lumen.
  • The amphiphatic bile acids assist in forming little droplets of fat surrounded by the hydrophilic part of the bile acid molecules.
  • These micelles offer a target for the gastric and pancreatic lipases that cleave the ester bonds and enable uptake into the cells.
• Once in the cell, the cellular machinery puts things back together again (re-esterification), packages fat with protein carriers (apolipoproteins), which are released as chylomicrons or VLDL into the lymphatics.

Question 8

Fat Absorption:
Micelle (p.61)

Answer 8

• Bile acids are amphiphatic.
• Bile emulsifies ingested fat thereby enhancing absorption.
• This is due to micelle formation (small lipid droplet in water with polar heads of amphiphatic molecules creating the interface between water and the hydrophobic core).
• Micelles are targets for lipolytic enzymes.

Question 9

Paracellular Transport (p.67-72)

• Epithelial cells express specialized proteins that form the tight junctions in the apical area between cells.
  
  • These multimeric proteins/
  • paracellular permeability
• what alters this permeability
  
  • the expression of tight junction proteins decreases when/
  • larger molecules/
    *

Answer 9

• Epithelial cells express specialized proteins that form the tight junctions in the apical area between cells.
  
  • These multimeric proteins are connected to the cytoskeleton and contain contractile elements that can dynamically regulate the tightness of these junctions.
  • Therefore, paracellular permeability can change (increase or decrease) based on regulatory signals
• Luminal factors (e.g. glucose load), nerve activity and inflammatory mediators alter this permeability.
  
  • the expression of tight junction proteins decreases when cells are exposed to an inflammatory mediator.
    
    • This increases permeability and may contribute to diarrhea.
  • larger molecules may get passed the epithelial barrier and trigger secondary immune reactions.
    
    • This may explain why many patients with diarrheal illness have increased titers to gliadin, a protein in wheat and other grains.

Question 10

Regulation of Intestinal Function:
Neural Factors (p.74-76)

• The complex functions of the small intestine are regulated by/
• Neural control:
  
  • Extrinsic and intrinsic nerves regulate/
  • The main transmitters triggering secretion
  • secretagogues
  • what decrease secretion and thus indirectly enhance absorption
• Neural Factors
  
  • Secretory
  • Anti-secretory

Answer 10

• The complex functions of the small intestine are regulated by nerves, hormones (locally and systemically produced) and immune cells.
• Neural control:
  
  • Extrinsic and intrinsic nerves regulate blood flow, secretion, absorption and motility.
  • The main transmitters triggering secretion are acetylcholine and VIP.
  • ATP, Substance P and serotonin also function as secretagogues.
  • somatostatin, enkephalins and norepinephrine decrease secretion and thus indirectly enhance absorption.
• Neural Factors
  
  • Secretory
    
    • Peptides (VIP, SP, NT)
    • 5-HT
    • Acetylcholine
    • ATP
  • Anti-secretory
    
    • Peptides (NPY, SOM, Enk)
    • Norepinephrine

Question 11

Regulation of Intestinal Function:
Enteric Hormones (p.79-80)

• ?
• stored in/
• trigger for release
• Enteric Hormones summary

Answer 11

• Specialized cells within the intestinal epithelium produce peptide hormones
• stored in small vesicles on the basolateral site and released upon stimulation.
• chemical stimuli (e.g. fat or protein) function as the trigger for release.
  
  • These hormones function as paracrine signals, meaning they affect neighboring cells.
  • They can acutely alter secretion / absorption, motility or blood flow.
  • they affect nerves which may activate reflexes (e.g. pancreatic secretion, ileal break) or contribute to a sense of satiety.
• Enteric Hormones summary
  
  • There are many of them!
  • They signal to mucosa, regulating function and growth.
  • They signal to muscle and glands (distant sites).
  • They signal to nerves regulating function (motility, secretion).
  • They signal to the brain regulating feeding behavior (a key to the obesity epidemic?).

Question 12

Regulation of Intestinal Function:
Examples of Enteric Hormones (p.81-87)

• CCK (cholecystokinin)
• PYY
• ghrelin

Answer 12

• CCK (cholecystokinin)
  
  • ability to trigger gall bladder contraction.
  • Release is triggered by fat, protein or amino acids within the proximal small bowel.
  • An increase in CCK stimulates gall bladder contraction, pancreatic secretion, intestinal motility and inhibits gastric emptying.
  • plays a role as a satiety signal.
• PYY
  
  • released by luminal nutrients and decreases gut motility.
  • important in slowing down movement into the colon (‘ileal break’).
  • decreases food intake.
• ghrelin
  
  • ​increases prior to eating
  • linked to the regulation of food intake.
  • increases gastric emptying

Question 13

Regulation of Intestinal Function:
Hormones (p.88-89)

• Hormones
• physiologic importance of such regulatory mechanisms
  
  • During lactation
  • switch in brush border disaccharideses

Answer 13

• Hormones
  
  • alter intestinal function.
  • well established for diseases, such as hypo- or hyperthyroidism.
  • role in the regulation of absorption (e.g. leptin decreases Apo-IV expression and thereby fat absorption).
• physiologic importance of such regulatory mechanisms.
  
  • During lactation, the increased energy demands are associated with an upregulation of glucose uptake.
    
    • Luminal exposure to glucose may further enhance absorptive mechanisms.
  • switch in brush border disaccharideses.
    
    • The glucocorticoid dexamethasone significantly increases the expression of sucrase-isomaltase, suggesting that stress-induced (=weaning) activation of the hypothalamic-pituitary-adrenal axis may play a role in regulating the differential presence of these enzymes.

Question 14

Regulation of Intestinal Function:
Immune System (p.91-93)

• The intestine
  
  • in constant contact with/
  • lymphoid organ
• Immune cells
  
  • found
  • produce/
• epithelial cells can produce substances that/
• Immune Cells
  
  • Secretory
  • Changes in gene expression

Answer 14

• The intestine
  
  • in constant contact with potential pathogens and antigenic substances.
  • the largest lymphoid organ of the body.
• Immune cells
  
  • found in close proximity to the epithelium
  • produce mediators that affect epithelial structure and function.
• epithelial cells can produce substances that may attract or activate immune cells.
  
  • Examples for this interaction are the down-regulation of absorptive proteins (e.g., Na+/K+ATPase; NEH2 & 3) in cells exposed to interferon γ or the activation of secretion by prostaglandin E.
• Immune Cells
  
  • Secretory
    
    • 5-HT
    • Prostaglandins & Leukotrienes
    • Histamine
    • Bradykinin
  • Changes in gene expression
    
    • TNF
    • Interferons & interleukins

Question 15

Intestinal Motility (p.94-103)

• A normal motor function of the intestine is critical for the absorptive process
  
  • During the fasting state/
  • This stereotypical pattern (the MMC, migrating motor complex)
  • Food intake/
  • Loss of this normal motility/
• Fasting Pattern

Answer 15

• A normal motor function of the intestine is critical for the absorptive process.
  
  • During the fasting state, regularly repeated waves of contractions move luminal contents distally, thereby contributing to the low level of bacterial colonization.
    
    • This is important as bacteria would compete for nutrients with the absorptive cells and potentially induce inflammatory changes.
  • This stereotypical pattern (the MMC, migrating motor complex),
    
    • lasts about 90 – 120 min
    • characterized by quiescence (phase I), followed by irregular (phase II) and then maximal activity (phase III).
  • Food intake disrupts this pattern and results in prolonged irregular activity that assures mixing and propagation of ingested materials.
  • Loss of this normal motility due to inherited or acquired diseases leads to intestinal pseudo-obstruction.
    
    • These patients have severely distended loops of intestine and often require parenteral nutrition as their own intestinal function has failed.
• Fasting Pattern
  
  • MMC (migrating motor complex)
  • Duration about 90 – 120 min (longer at night)
  • Maximal contraction frequency 12 / min

Question 16

Summary

• Nutrient, water and electrolyte absorption are/
• You can find/
• The regulation of absorption and secretion involves/
• Factors regulating absorption also contribute to/
• Things have to move through (motility) to allow/

Answer 16

• Nutrient, water and electrolyte absorption are coupled.
• You can find a regional specialization of absorptive pathways.
• The regulation of absorption and secretion involves nerves, hormones, immune cells and luminal factors.
• Factors regulating absorption also contribute to the regulation of food intake.
• Things have to move through (motility) to allow absorption to take place.