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Flashcards in 17 Small Bowel Physiology Part 2 Deck (16):
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

  • 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.

2

Carbohydrate Absorption (p.39-40)

  • chemical fragmentation of carbohydrates
  • Maltose and disaccharides

  • 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.

3

Carbohydrate Absorption (p.41-45)

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

  • 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 

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

  • 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.

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

  • 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.

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/

  • 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.

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/

  • 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.

8

Fat Absorption:
Micelle (p.61)

  • 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.

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/
    •  

  • 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.

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

  • 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

11

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

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

  • 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?).

12

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

  • CCK (cholecystokinin) 
  • PYY 
  • ghrelin 

  • 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

13

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

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

  • 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.

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

  • 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

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

  • 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

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/

  • 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.