Allison Siebecker Lecture Flashcards
IBS effects what % of Americans?
up to 20%; 50% visit gastroenterologist
What is IBS?
Irritable bowel syndrome
Sx: bloating, pain, constipation, diarrhea or mixture both
Thought to be caused by GI infection in most cases; results in SIBO (small intestinal bacterial overgrowth)
What are the underlying mechanism of SIBO?
carbohydrate malabsorption from SIBO
What is digestion?
breaking down food into smallest particles, mechanically by chewing, chemically by acids and enzymes
What are the acids & enzymes involved in digestion?
- HCl and pepsin in stomach & bile from Liver & gallbladder in small intestine
- enzymes from pancreas in small intestine
- enzymes that sit on the small intestine BB
What is absorption?
- movement of smallest particles of food across SI lining (1 cell thick)
- food particles go through the cell via transporters & into blood/lymph circulation on the other side
- transporters can get overwhelmed OR too few ‘doorways’
What is the order of the segments of the SI?
- duodenum
- jejunum
- ileum
What are the two types of ilieoecal valves?
papillary & labial
What are the three parts of the SI?
lumen, folds, villi
What makes up the villi of the stomach?
microvilli= brush border
What are the two cells of the pancreas which secrete substances?
- acinar cell–> secrete digestive enzymes
- duct cells secrete water & bicarbinate (NaHCO3)
What does the pancreatic duct drain and into what structure?
enzymes, water & bicarb into the SI
What are the Islets of Langerhans for (what do they secrete & into where)?
secrete hormones (insulin & glucagon) into the blood
Digestion beings with what?
pancreas secretions
What are bicarb & H2O for in terms of digestion?
neutralize acid from stomach
What are the pancreatic enzymes for?
digest the food
What stimulates the release of pancreatic enzymes?
neuroendocrine system
What are the 3 pancreatic phases?
- cephalic
- gastric
3.
What is the cephalic phase?
- before food in mouth & once food in mouth
- vagus stimulates pancreatic secretions in response to reflexes
What are the reflexes which stimulate pancreatic secretions
- smell
- taste
- chewing
- swallowing
What is the gastric phase?
- food in the stomach
- vagus stimulates pancreatic secretion in response to gastric distention
What is the intestinal phase?
- most important phase!
- digestive products trigger release of hormones that control secretion
- CCK: released from I cells, stimulates enzyme & bile secretion for digestion
- Secretin: released from S cells, stimulates water and bicarb secretion to neutralize acid
- parasympathetic procsses (stress inhibits secretion)
What stimulates CCK secretion?
fat, protein (peptides/amino acids)
What stimulates secretin secretion?
H+ (acid), fat
SI CHO & Protein digestion occcurs in how many and what phases?
- 2 phases
- pancreatic enzymes (& bile from liver) in lumen break big into smal
- brush border enzymes on membrane break small into single units for absorption
What are the monosaccharides?
- glucose, fructose, galactose
- 1 sugar
What are the disaccharides?
- sucrose: fructose, glucose
- lactose: glucose, galactose
- 2 sugars
What are the oligosaccharides?
- FOS, GOS, MOS
- few, 3-10 sugars
What are polysaccharides?
- starch, fiber
- many, 10+
What dietary carbs can humans not digest?
fiber & oligosaccharides–> we don’t have the enzymes to break bonds between the sugars
Humans can digest…
- starch (amylose, amylopectin): rice, potato, corn, wheat, etc.
- sucrose: table sugar
- lactose: milk sugar
- trehalose: mushrooms, honey, shrimp/lobster, algae, insects, rye
- glucose: honey, fruit, veggies
- fructose: HFCS, agave, honey, fruit, veggies
What are the 6 major carbohydrases?
amylase, isomaltase, maltase, sucrase, lactase, trehalse
Describe amylase
- source: pancreas
- site of action (SOA): duodenal lumen
- substrate: starch
- end product: dextins, maltotriose, maltose
Describe isomaltase
- source: BB
- SOA: brush border
- substrate: dextrin, maltotriose
- end product: maltose
Describe maltase
- source: BB
- SOA: BB
- substrate: maltose
- end product: glucose, glucose
Describe sucrase
- source: BB
- SOA: BB
- substrate: sucrose
- end product: glucose, fructose
Describe lactase
- source: BB
- SOA: BB
- substrate: lactose
- end product: glucose, galactose
Describe trehalse
- source: BB
- SOA: BB
- substrate: trehalose
- end product: glucose, glucose
What are the 3 carbohydrate transporters?
- SLGT1= glucose, galatose; high affinity, active transport (ATP required)
- Glut 5= fructose; facilitated diffusion (easily saturated)
- Glut 2= glucose, galactose & fructose; backup= fructose when Glut 5 is overwhelmed; exiting= transports out of enterocyte to blood; facilitated diffusion
What forms of carbs can be absorbed? What is carbohydrate malabsorption caused by?
monosaccharides only! dis and anything larger can’t transport across the BB (need BB enzymes to digest dis & larger to monos or they will become food for bac= carbohydrate malabsorption)
What is carbohydrate malabsorption?
when CHOs are left in lumen of SI & LI, bac then ferment them= GAS, also CHOs sitting in lumen draw in water= DIARRHEA–> triggers bloating, constipation/diarrhea, pain, nausea, flatulence, belching, GERD, fatigue
What do bacteria produce in relation to GI malaise?
-hydrogen, methane= gas & bloating-> abdominal pain, gas exiting via mouth or anus, altered motility
What is the difference b/w primary and secondary lactose malabsorption?
- primary= genetic, congenital, born w/o lactase
- secondary= damage, loss of lactase after wearing, due to DAMAGE, leaves lactose in the SI
What is fructose malabsorption?
- fructose transporter, Glut 5 gets easily saturated (facilitated diffusion has limited capacity)
- 15 g absorbed in healthy ppl (5-50 g range)
- well absorbed w/glucose in 1:1 ratio by Glut 2
- seeing increase in occurence b/c of increased consumption of fructose
Why could CHO malabsorption occur?
- no enzyme to digest it (oligosaccharides)
- decreased enzymes (genetic= primary= lactose & fructose intolerant OR damage= secondary= BB enzymes may be effected)
- inefficient absorption by transporters
- substance too large= polyols/sugar alcohols
- too fast of transit
- bacterial overgrowth/imbalance
SI protein digestion occurs in how many phases & what are they?
2 phases
- pancreatic enzymes in SI lumen= trypsin, chymotrypsin, elastase (protein–> polypeptides, 2-6 a.a.s long) AND carboxypeptidase A & B (polypeptides–> amino acids)
- BB enzymes= aminopeptides (peptides (2-3 a.a.s long)–> amino acids
What are the 5 major SI proteases and the one BB? And their proenzyme form?
- trypsin (trypsinogen)
- chymotrypsin (chymotrypsinogen)
- elastase (proelaste)
- carboxypeptidase A (procarboxypeptidase)
- carboxypeptidase B
- BB: aminopeptidase (simply activated by a.a.s, dis & tris)
Pancreatic enzymes are secreted in what form & why?
zymogens (proenzymes) so as to not digest the pancreas itself
What activates trypsin?
enteropeptidase/enterokinase (BB enzyme), released by detergent action of bil (fat helps protein digestion)
What are the protein transporters? What absorbs?
- numerous BB transporters for a.a.s
- a.as, dis & tris absorb BECAUSE of peptidases w/in the enterocytes
What does protein malabsorption lead to?
leads to muscle wasting, immunodeficiency & edema in its severe form (not GI sx’s like with CHO malabsorption b/c bac can’t ferment protein)
What are the 3 ‘parts’ of cell junctions?
- zonula occludens
- zonula adherens
- macula adherens (desmosome)
What is the tight junction structure?
- caludins, occludens, JAM (junctional adhesion molecules)
- attached to zonulin 1 & 2 anchors
- attached to actomysin filaments
What are the functions of tight junctions?
- gate: regulate passage of macro & micro molecules through paracellular space b/w cells
- fence: keeping microbiotia & large substances out for protection
* *TJ permeability constantly changes
What is increased intestional permeability? What happens?
- when TJs b/w cells ope= allow unintended items through
- absorption of unintended items can also occur through cell itself
Paracellular vs Transcellular
Paracellular: between two cells
Transcellular: through the cell to the other ‘side’
What opens the TJs?
contraction of actin
What is leaky gut? What can it lead to?
- allows absorption of things that are not supposed to be getting in: partially digested food particles, baceria & bacterial toxins, viruses, yeast, metabolites & acids
- leads to immune rxns & sxs anywhere inside the body
- *intestinal permeability causes systemic symptoms & is the main cause of food rxns
- *can have leaky gut w/o sx’s
What are the seven broad categories that can lead to increased intestinal permeability?
- diet
- medications
- infections
- stress
- hormonal
- neurological
- metabolic
bonus: NSAIDS!!!
Take homes
- digestion occurs by pancreatic & BB enzymes
- absorption occurs through transporters
- saccs need BB enz digestion into monos to be absorbed
- peptides can absorb since they will be digested into a.a.s inside the enterocyte
- pancreatic proteases need activation (so don’t digest pancreas) BUT amylases don’t
- gluc absorbs efficiently via SGLT but fruc may nto due to saturability of GLUT5
- stress inhibits digestion (HCl, bicarb, bile, enz) & increases intestinal permeability which leads to systemic sx’s from food/eating
