GI Phys Flashcards
the GI tract is (mobile/motile) to move and mix contents for digestion and absorption
motile
digestion
breaking down food/high-molecular weight substances into small molecules
absorption
transport of digestive products across intestinal epithelium
secretion
release of substances into lumen of GI tract to facilitate digestion/absorption/motility
functions of GI tract are interdependent to optimize _______
absorption
functional segmentation
continuous tube is separated into segments with unique functions
accessory organs examples (4)
salivary glands, liver, pancreas, gallbladder
accessory organs functions
secrete substances into GI tract to facilitate digestion/absorption (anatomically distinct)
9 layers of intestinal wall (cross-section)
epithelium, basement memb., lamina propria, muscularis mucosae, submucosa, circular muscle, myenteric plexus, longitudinal muscle, mesothelium
epithelium function
cell barrier nutrients transverse to be absorbed
2 circulatory structures that transport substances between tract and rest of body
capillaries and lymphatics
circular/longitudinal muscle function
allow motile contractions
myenteric plexus function
nerve supply controlling motility/secretion
endocrine cells function
secrete hormones into blood for digestion/appetite
exocrine/acinar cells function
secrete digestive substances/enzymes into gut lumen
mucous cells function
form ducts to connect lumen of GI tract to accessory organs
sphincters form/function
rings of muscle that constrict GI tube; regulate flow, prevent backflow
6 sphincters of GI tract
- upper esophageal (pharynx/eso.)
- lower esophageal (eso./stomach)
- pyloric (stomach/ sm. intes.)
- ileocecal (sm. intes./lg. intes.)
- internal anal (rectum/anus)
- external anal (rectum anus)
3 mouth functions
mechanical food breakdown, preparation for swallowing and onset of digestion
mouth: mastication definition
chewing (teeth/facial muscles)
mouth: prep. for swallowing
moistening bolus with saliva
mouth: onset of digestion
enzymatic breakdown via salivary amylase
swallowing reflex controlled by ___
ANS
swallowing: oral phase
voluntary collection of food bolus into pharynx by tongue
swallowing: pharyngeal phase
involuntary contractions of pharyngeal muscles, pushes bolus into esophagus
swallowing: esophageal phase
peristaltic wave moves bolus down esophagus (~4cm/s)
swallowing: additional reflex functions (2)
glottis closure and respiration inhibition
4 step process of swallowing
- tongue moves bolus to back of mouth, tiggers reflex (oral phase)
- soft palate elevates to prevent food from entering nasal passage (pharyngeal phase)
- epiglottis covers glottis, preventing bolus entry into trachea, upper eso. sphincter relaxes (pharyngeal phase)
- food descends eso. (eso. phase)
3 stomach funcitons
storage, continued digestion, regulate emptying into sm. intes.
2 sections of stomach
fundus (top) and antrum (mixing)
lower eso. sphincter function
control food entry to stomach and prevent reflux
stomach: mechanical digestion form
peristaltic waves vie rugae (folded surfaces)
stomach: chemical secretions (2)
HCl, pepsin
stomach: HCl functions (2)
acidity denatures proteins (more soluble) and cleaves pepsinogen to pepsin
pepsin
enzyme that breaks down proteins
chyme
ingested food that leaves stomach
3 sections of sm. intes.
duodenum (20cm), jejenum (2.5m), iluem (3m)
sm. intes. function
primary site of digestion
sm. intes. maximizes food ________
absorption
______ enzymes aid digestion in sm. intes.
hydrolytic
sm. intes. form to incr SA (4: biggest to smallest)
tube>circular folds>villi>microvilli (increases SA - 600 fold)
brush border is composed of
microvilli
incr. SA allows for…
incr. contact for digestrion/absorption
lg. intes. function
store and concentrate undigested material
lg. intes. form (7)
cecum, appendix, asc. colon, transverse colon, desc. colon, sigmoid colon, rectum
cecum form/function
first part of lg. intes.; small in humans, cellulose digestion in herbivores
appendix function
reserve for healthy gut bacteria (restore microflora after diarrhea)
asc., transverse, desc., sigmoid colon functions
absorption of ions and water; bacterial metabolism
rectum function
holds feces before defecation
salivary glands: 3 types
sublingual (under tongue), submandibular (under jaw), parotid (beside ear)
salivary glands: general form
empty into oral cavity
salivary glands: function
secrete water and mucus to moisten and lubricate bolus; amylase to digest large carbs.
liver and gallbladder: form
empty into sm. intes. via bile duct
liver: secretions and functions (4)
bile salts digest fats, bicarbonate neutralizes acidic chyme, org. waste products and trace metals for elimination
gallbladder: 3 functions
stores, concentrates (absorbs H2O and NaCl) and releases bile
exocrine pancreas: form
(digestive system) acinar cells secrete enzymes into sm. intes. via pancreatic duct
endocrine pancreas: form
(endocrine system) islet cells of Langerhans secrete hormones into blood (ex: insulin)
pancreas: secretions and functions (4)
bicarbonate neutralizes chyme, pancreatic amylase digests carbs., trypsinogen+chymotrypsin digest proteins, pancreatic lipase digests fats
peristalsis/peristaltic wave
rings of contraction that pass along the length of the GI tract, force lumenal contents forwards
segmentation
constriction of GI tract in situ to mix contents (no net movement, ie. back and forth)
peristaltic reflex triggered by…
lumenal contents stretching intestinal wall, causing contraction behind and relaxation in front of bolus
peristaltic reflex independent of…
external innervation but modulated by ANS input
peristaltic reflex dependent on…
ENS activity
peristaltic response steps (3)
- local stretch response releases serotonin (activates sensory neurons that activate myenteric plexus)
- “upstream” neurons activated and release factors for smooth muscle contraction
- “downstream” neurons activated and release factors for smooth muscle relaxation
2 factors that cause smooth muscle contraction in peristalsis
substance P and acetylcholine
2 factors that cause smooth muscle relaxation in peristalsis
NO and vasoactive intestinal polypeptide
segmentation primarily occurs in the…
small intestine
segmentation response steps (3)
- initial contractions separate contents into pockets
- next contractions separate pockets centrally
- rhythmic contractions continue to subdivide pockets
BER stands for
basic electrical rhythm
BER form and function
pacemaker cells (interstitial cells of Cajal); rhythmic oscillations in Vmemb. of smooth muscle cells causes contractions for segmentation
2 factors affecting BER rate
- acetylcholine: INCR activity and contraction
2. epinephrine: DECR activity and contraction
rate of BER in stomach, duodenum, ileum, cecum and sigmoid colon respectively (#/min)
4/min, 12/min (fastest), 8/min, 2/min (slowest), 6/min
MMC occurs after…
segmentation and food has been absorbed
MMC
migrating myoelectric complex
MMC function
move undigested contents in sm. intes. to lg. intes.
what is the MMC?
final sweeping wave of contractions from stomach to sm. intes. in 2ft long sections
MMC duration
~2 hours
3 phases of MMC
- quiescent period (during digestion and absorption)
- irregular elec./mech. activity
- regular elec./mech. activity
MMC is inhibited by… and why?
ingestion of a meal; want food to stay in sm. intes. for digestion and absorption
hormone that controls MMC
motilin (in plasma)
motilin secretion is inhibited by…
ingestion
LES activity
tonically active, relaxes to allow food entrance to stomach
why is the LES tonically active?
prevent stomach reflux into eso.
3 components of LES and definitions
- internal sphincter: thickening of eso. smooth muscle
- external sphincter: crural portion of diaphragm surrounds eso.
- clasp/sling fibers: stomach wall muscles
LES
lower eso. sphincter
VIP
vasoactive intestinal polypeptide
3 factors that affect LES contraction/relaxation
ACh: contracts
NO and VIP: relaxes
receptive relaxation
stomach relaxation to allow incr V without incr P (compliance)
overfilling of stomach effects
belching or vomiting
gastric peristalsis function
mixes stomach contents and pushes them through pyloric sphincter
gastric peristalsis generated by…rate?
basic electrical rhythm (F is extrinsically controlled); ~3/min
gastric peristalsis process
starts at top of stomach and incr in size as it moves down, forces pyloric sphincter closed with some liquid chyme forced through
4 extrinsic factors controlling gastric emptying
stomach/intestinal contents, acidity, distension, hypertonicity
stomach contents effect on gastric emptying
meals rich in protein or fat delay gastric emptying
acidity effect on gastric emptying
acidity inhibits gastric emptying (feedback loop w/ duodenum)
distension effect on gastric emptying
stomach distension incr peristaltic contractions, duodenum distension inhibits gastric emptying
chyme tonicity in intes. effect on gastric emptying
isotonic duodenal contents incr gastric emptying; hypertonic decr gastric emptying
belching/aerophagia
physiological venting of gastric air
belching/aerophagia cause
air swallowed during drinking or eating
belching/aerophagia process
air in stomach incr gastric V, reflex response relaxes LES allowing air to escape
vomiting/emesis
involuntary, forceful expulsion of stomach contents out of mouth
vomiting/emesis regulators (2)
CNS: nucleus tractus solitarius and brain stem vomiting center
vomiting/emesis process (4)
- salivation and nausea
- reverse peristalsis starts from intestine and sweeps upwards
- ab. wall muscles contract (incr P)
- sphincters and eso. relax
5 vomiting/emesis triggers
digestive, sensory, emetics, social cues, miscellaneous
digestive vomiting/emesis triggers ex
gastroenteritis, bowel obstruction, food allergy
sensory vomiting/emesis triggers ex
motion sickness, viral infection, morning sickness, drug rxn
emetics
medically administered drugs to prevent poisoning by causing vomiting/emesis
social cues vomiting/emesis trigger ex
emotional distress
miscellaneous vomiting/emesis triggers ex
nauseating sights/smells, anxiety
different vomiting/emesis triggers act through _____ neural pathways
different
1 minor and 3 major forms of sm. intes. motility
minor: peristalsis
major: segmentation (during digestion), MMC, tonic contractions
sm. intes. segmentation controlled by
BER (basic electric rhythm)
tonic contractions are… and why?
prolonged contractions that can isolate segments of sm. intes.; incr t for absorption
sm to lg. intes. valve name and function
ileocecal valve; one-way to prevent backflow (incr colon P closes it, incr ileal P opens it)
gastroileal reflex
opening of ileocecal valve when food leaves stomach
lg. intes. motility (4)
segmentation, peristalsis, mass action contractions, defecation
mass action contractions and rate
simultaneous contractions of large areas of colon; 10/day
mass action contractions function
move material through colon and to rectum
defecation reflex caused by…
incr rectal P caused by mass action contractions (desire to defecate)
2 anal sphincter differences
internal: involuntary, smooth muscle
external: voluntary, skeletal muscle
defecation process
incr rectal P causes internal anal sphincter to relax and external to contract
> 55mm Hg P in rectum causes what to happen?
external anal sphincter reflexively relaxes and feces is released
voluntary contraction of external anal sphincter causes…
feces to move back into sigmoid colon due to prolonged distention, urge to defecate subsides until next mass action contraction
voluntary contraction of ab. muscles and relaxation of puborectalis causes..
descent of pelvic floor and opening of anorectal angle to facilitate defecation
best position to defecate and why?
squatting (not sitting); decr P and incidence of hemorrhoids and diverticular disease
transit time through GI tract avg for adults and children
adults: >50 hours
children: ~33 hours
transit time through GI tract variables
type of food and health status (diarrhea and constipation)
transit time through stomach, sm. intes. and colon (hours)
stomach: 4-5 hours
sm. intes. 2.5-3 hours
colon: 30-40 hours
(~2 days total)
4 factors of luminal comp. that affect GI responses
V of luminal contents, osmolarity, acidity, nutrient comp.
V of luminal contents: receptor type and effector
(distension) mechanoreceptors, smooth muscle cells
osmolarity: receptor type and effector
([solute]) osmoreceptors, exocrine glands
acidity: receptor type and effector
(pH) chemoreceptors, exocrine glands
nutrient comp.: receptor type and effector
(macromolecule type) chemoreceptors, exocrine glands
2 plexuses of ENS
submucosal and myenteric plexuses
difference btwn short and long reflexes
short reflexes: signal within ENS
long reflexes: signal integrated with CNS
enteroendocrine cells: form
cell in intestinal wall: apical side faces lumen, basolateral side faces interstitial space
enteroendocrine cells: function
receive stimuli from intestinal lumen and secrete hormones into interstitial space->bloodstream
4 GI hormones
gastrin, cholecystokinin, secretin, glucose-dependent peptide
CCK stands for…
cholecystokinin
GIP stands for…
glucose-dependent insulinotropic peptide
gastrin: site of production
stomach
gastrin: production trigger
aa/peptides
gastrin: response in stomach
stimulates HCl secretion and motility
CCK: site of production
sm. intes.
CCK: production trigger
aa and fat
CCK: response in stomach
inhibits acid secretion and motility
CCK: response in pancreas
stimulates enzymes secretion
CCK: gallbladder response
stimulates contraction of gallbladder and relaxation of sphincter of Oddi (to secrete bile)
secretin: site of production
sm. intes.
secretin: production trigger
acidity
secretin: response in stomach
inhibits HCl secretion and motility
secretin: response in pancreas and liver
stimulates release of HCO3
GIP: site of production
sm. intes.
GIP: production trigger
glucose and fat
GIP: response in pancreas
stimulates insulin secretion
3 phases of GI regulation
cephalic, gastric, intestinal
cephalic phase
sight, smell, taste of food stimulates brain
gastric phase
distension, acidity, aa/peptides stimulates stomach
intestinal phase
distension, acidity, osmolarity, digestive products stimulates intestine
approx. daily volume of secretions into GI tract
~7 L (vs 1.2 L daily fluid intake)
approx. daily volume of fluid lost in feces
~0.1 L (majority of fluid is reabsorbed)
major producers of secretions into GI tract
accessory glands (salivary glands, liver, gallbladder, exocrine pancreas)
approx. daily V of salivary secretions
1.5 L
5 saliva components
water (98%), electrolytes, mucus, enzymes, immune modulators
water, electrolytes and mucus function in saliva
lubrication to protect oral cavity and ease of swallowing
immune modulators function in saliva
antibacterial antibodies, WBCs, etc. to kill pathogens
salivary secretion regulation during the ______ phase
cephalic
salivary secretions regulated by ___ nervous system
autonomic (para/symp)
para vs symp regulation of salivary secretion viscosity
symp: thicker
para: watery
para vs symp regulation of salivary secretion viscosity function
symp: thicker = respiration
para: watery = digestion
para vs symp regulation of salivary secretion primary NT
symp: NE
para: ACh
symp regulation of salivary secretion ex (anxiety)
anxiety = incr symp. activity = decr salivation/thickening = dry mouth
para regulation of salivary secretion ex
appetizing food = incr para = incr salivation
approx. daily V of gastric secretions
2 L
4 components of gastric secretions
Mucus, HCL, enzymes, hormones
gastric mucus function
lubricates and protects stomach lining
gastric HCl function (3)
solubilizes food (proteins), kills ingested microbes, cleaves pepsinogen to pepsin
gastric enzyme ex and function
pepsin (proteolytic enzyme-cleaves proteins)
gastric hormones function
regulate other gastric secretions (secreted into blood not stomach)
gastric 2 types of mucus-producing cells
surface and neck mucus cells
gastric HCl-producing cells
parietal cells
gastric histamine-producing cells
enterochromaffin-like (ECL) cells
gastric pepsinogen-producing cells
chief cells
5 cells in gastric gland from inside->out
chief, ECL, parietal, mucous neck, surface mucous
HCl production is mediated by which 2 phases
cephalic and gastric
3 compounds that stimulate HCl/H+ production from parietal cells
gastrin, histamine, ACh
compound that inhibits HCl/H+ production from parietal cells
somatostatin
how do compounds that stimulate/inhibit HCl/H+ production from parietal cells work?
via 2nd messengers, binding of ligand stimulates exocytosis of vesicles with H+/K+-ATPase pumps onto cell pmemb.
what are 2 ways that HCl/H+ production from parietal cells is stimulated?
G-cells in intes. epi produce gastrin (after high protein meal), enters circulation and stimulates parietal cells to produce HCl directly or through ECL cells by incr histamine production
what did the experiments on Alexis St. Martin by William Beaumont show?
the stomach could digest food without the mouth’s chewing
approx. daily V of pancreatic secretions
1.5 L
2 components of pancreatic juice
bicarbonate and enzymes
pancreatic bicarbonate function
neutralizes chyme
pancreatic enzymes function
breakdown macromolecules
pancreatic duct cells secrete
bicarbonate
main pancreatic duct: form
drains pancreatic glands and merges with common bile ducts from gallbladder and liver before entering sm. intestine
pancreatic secretions are controlled in which phase
intestinal (with cephalic and gastric inputs)
if the chyme is acidic, what will the sm. intes., pancreas and liver secrete? (+feedback loop)
sm. intes. produces secretin which incr pancreas+liver bicarbonate production, sm. intes. is neutralized which feedback inhibits sm. intes. secretin production
if there is lots of intes. fa and aa, what will the sm. intes. and pancreas secrete? (+feedback loop)
sm. intes. produces CCK which incr pancreas enzyme production, sm. intes. has incr digestion which feedback inhibits sm. intes. CCK production
how do hormones travel/signal between the sm. intes. and pancreas?
blood (in plasma)
approx. daily V of bile from the liver
0.5 L
bile is produced by the…
liver
bile is stored in the…
gallbladder
7 components of bile
water (97%), bile salts, bile pigments, cholesterol, inorganic salts, fa, and phosphatidylcholine
bile salts function in bile
solubilize water-insoluble fats (cholesterol)
bilirubin function in bile
product of Hb breakdown (excreted)
fat form and function in bile
phospholipids (cholesterol and lecithin), aid fat digestion
how does bile accumulate in the gallbladder?
continuously produced by liver in dilute form, some diverted into gallbladder or builds up when sphincter of Oddi is closed (cant flow into duodenum)
what is absorbed from bile in the gallbladder?
water and salts (NaCl), making it more concentrated
in response to CCK the gallbladder…
contracts and sphincter of Oddi relaxes, bile enters duodenum
during what phase is bile secretion regulated?
intestinal
how is bile secretion regulated in duodenum and gallbladder?
if duodenum has high [fa], incr CCK secretion, gallbladder secretes bile (into common bile duct) and sphincter of Oddi relaxes (flows into duodenum)
approx. daily V of intestinal secretions
1.5 L
3 components of intestinal secretions
water/electrolytes, mucus, and enzymes
water/electrolytes function in intes. secretions
maintains fluidity of intes. contents
mucus function in intes. secretions
lubrication and protection of epithelium lining
enzymes function in intes. secretions
aids digestion
what drives water secretion in intes.?
osmosis
what are intestinal crypts?
invaginations of intes. wall surrounding base of villi
diff btwn function of crypts vs villi?
crypts: secretory function
villi: absorptive function
what do epi. cells in crypts secrete?
ions: Na, Cl, HCO3, water follows by osmosis
how does chyme leaving stomach affect osmolarity of sm. intes.?
high [solute] creates hypertonic enviro and pulls water from plasma by osmosis
how much of GI secretions are absorbed?
6.7 L (most)
which 3 types of macronutrients are required in the diet?
fats, carbs, protein
what is the cal/g ratio for carbs?
4 cal/g
what is a non-digestible carb?
dietary fiber
what does hydrolyzed lactose form?
glucose + galactose
what does hydrolyzed maltose form?
2 glucose
what does hydrolyzed sucrose form?
glucose + fructose
why can’t cellulose be digested?
alternating orientation of glucose residues, linked by H-bonds, makes it harder for catalytic enzymes to cleave them
what is the cal/g ratio for dietary fats?
9 cal/g (most)
what is the most abundant type of dietary fat?
triglyceride (~90%)
what is the structure of triglycerides?
glycerol + 3 fa
what 3 forms of triglyceride fatty acids are there?
saturated, mono-unsaturated, poly-unsaturated
what is the cal/g ratio for proteins?
4 cal/g
what is a major feature of fats, carbs and proteins?
major source of energy
what differentiates proteins from fats and carbs?
more considered a building block than an energy source
what are supramolecular protein assemblies? and 3 ex?
multiple different proteins associated to form biological machines; protein complexes, myofilaments, collagen fibrils
what are 3 different types of micronutrients?
fat-soluble vitamins, water-soluble vitamins and trace elements
what are 3 ex of fat-soluble vitamins?
A, E, D
what are 2 ex of water-soluble vitamins?
B complex, C
what are 4 ex of trace elements?
iron, iodine, zinc, calcium
what specific type of enzyme is amylase?
alpha(1,4) endoglucosidase (cleaves glycosidic bonds btwn 4C and 1C in polysacc. to form oligo/disacc.)
where and what are brush border enzymes?
sm. intes.; enzymes on brush border of intes. epi. that are specific to different disacc.
what are the brush border enzymes for maltose, sucrose and lactose?
maltase, sucrase, lactase
what is lactaid? why is it used?
lactase enzyme; for lactose intolerance (deficiency of lactase, can’t breakdown lactose)
how are glucose and galactose absorbed in intes. epi cell? (2)
secondary active transport, SGLT-1
what is SGLT-1?
sodium-glucose cotransporter, imports 2 Na down conc grad. and 1 glucose/galactose up conc. grad. (2ndary active transport)
what is GLUT2
glucose transporter, exports glucose/galactose down conc. grad. (facilitated diffusion)
how and why are Na ions removed from intes. epi cell?
Na/K ATPase; to maintain low [Na] conc. inside cell for SGLT-1
what 2 transporters are on the apical side of the intes. epi. cell?
SGLT-1 and GLUT5
what 2 transporters are on the basolateral side of the membrane?
GLUT2 and Na/K ATPase
how is fructose absorbed? (2)
facilitated diffusion, GLUT5
what proteins transport fructose in vs out of the intes. epi. cell?
GLUT5 and GLUT2
what occurs during a high-sugar meal in an intes. epi. cell?
sugar gradients are saturated so GLUT2 is translocated from basolateral to apical side of cell to aid diffusion of sugar into cell (max. absorption)
what is the general summary of carb. digestion and absorption?
pancreatic amylase cleaves polysacc. to oligo/disacc. in intes. lumen, brush border enzymes cleave to monosacc. which are transported across intes. epi. cell
what are 3 ex of dietary fibers?
cellulose (plant cell walls), lignin (plant cell walls), chitin (cell walls of fungi & insect/crustacean exoskeletons)
what are 4 physl. effects of dietary fibers?
- delays gastric emptying and incr fullness
- decr absorption in sm. intes.
- fiber fermentation in lg. intes.
- fecal bulking
what are 3 effects of trapping, interfering, and inhibiting by dietary fibers (decr sm. intes. absorption)?
delays carb. absorption (better glucose control), impairs cholesterol absorption, trapping trace elements or toxic compounds
what is fiber fermentation?
gut microbiota can ferment undigested fiber to produce short-chain fa (energy source)
what is fecal bulking?
mass of undigested fiber can retain water and incr bacterial mass secondary to fiber fermentation
g of fat in avg. diet and % of cal. intake
65-95g; ~35%
what % of ingested fat is absorbed?
95%
what are triglycerides broken down into?
free fatty acids
what is a unique aspect of fat digestion?
lipids form large globules of fat in water and must be emulsified
emulsification requires what 2 things
- mechanical digestion
2. emulsifying agents
where are emulsifying agents contained? and what are they made of
bile; phospholipids and bile salts (amphipathic molecules)
what is lipolysis?
process of fat breakdown
what are the products of lipolysis?
monoglycerides and free fatty acids
what is lipolysis catalyzed by?
pancreatic lipases
why is colipase needed and what does it do
pancreatic lipase is water-soluble so colipase is required to hold pancreatic lipase to lipid droplet surface
what do the products of lipolysis form at high conc.?
micelles (combined with bile salts)
micelle formation and breakdown existing in an equil. allows for what?
small fraction of fat-digestion products to be dissolved in solution and absorbed
how do solubilized fa cross the intes. epi. cell memb? (2)
diffusion; “flip-flop”
what are chylomicrons?
repackaged triglycerides coated in apolipoproteins in intest. epi. for secretion (via exocytosis)
why are chylomicrons formed?
easier to transport throughout body vs free fa and monoglycerides
what is a summary of fat digestion and absorption? (4)
emulsification, lipolysis, diffusion, chylomicron formation and secretion
required vs avg. g of protein ingested
40-50, 60-90
where else does the intestine receive proteins other than from ingestion?
secreted into it from mucus, enzymes and degraded epi. cells
what % of protein is broken down into aa and absorbed?
95% (regardless of source)
what enzyme mediates protein digestion?
proteolytic enzymes (proteases)
what are 2 categories of proteases and the difference?
endopeptidases: cleave proteins at interior peptide bonds
exopeptidases: cleave proteins at n/c-termini
what must occur with proteases for them to work? why?
activation by other proteins in lumen; very powerful and cant always be active
what are the 2 types of exopeptidases?
aminopeptidases: cleave at n-term.
carboxypeptidases: cleave at c-term.
what are 3 examples of endopeptidases?
trypsin, chymotrypsin, elastase
where does protein digestion begin?
stomach
what 2 ways does the stomach initiate protein digestion?
acidic enviro denatures proteins, secreted pepsin cleaves large polypeptides (protease)
how is pepsin activated?
gastric acid cleaves pepsinogen to pepsin (stops in duodenum-alkali enviro)
what 2 proteases continue protein digestion in the sm. intes.?
pancreatic and intestinal brush border enzymes
what 2 molecules activate pancreatic enzymes?
enterokinase and trypsin
how does enterokinase work?
bound to intes. epi. and cleaves trypsinogen to trypsin
what can trypsin do? (2)
activate more trypsinogen (feedforward) and other pancreatic enzymes
what are 3 types of intes. brush border enzymes?
aminopeptidases, carboxypeptidases and endopeptidases (have specific types)
what do brush border enzymes cleave proteins into?
aa, di and tripeptides
how are di and tri peptides in intes. epi. cells broken down?
intracellular peptidases break down to aa
what 3 locations in the intes. does protein digestion occur? (cross-section)
lumen, brush border, epi. cells
what transport protein aids di and tripeptide absorption across the intes. epi?
PepT1 (peptide transporter 1)
how does PepT1 work?
secondary active transport of small peptides across intes. epi. with H+ (down grad.)
how do aa exit the intes. epi cells into the interstitial space?
facilitated diffusion (aa transporters)
what maintains the proton grad. for small peptide uptake in the intes. epi.?
NHE (apical Na/H exchanger - H out/Na in, both up grad.)
what maintains the Na grad. for small peptide uptake in the intes. epi.?
Na/K ATPase (maintain low intracell. [Na]), K exits via facilitated diffusion
what do transporters that facilitate aa uptake into intes. epi cells rely on?
secondary active transport with Na ions (down grad)
what is the difference btwn small peptide vs aa uptake into intes. epi. cell?
small peptide: secondary active transport coupled to H ions
aa: secondary active transport coupled to Na ions
what is a general summary of protein breakdown/absorption? (5)
proteins breakdown to small peptides or aa by pancreatic proteases/peptidases, small peptides broken down to aa by brush border enzymes, aa and small peptides transported into intes. epi. cells, small peptides broken down to aa by peptidases, aa exit via facilitated diffusion
what is vit C also known as?
ascorbic acid
where are majority of water-soluble vit absorbed?
first part of small intes
how are water-soluble vit absorbed?
coupled to sodium cotransporters (except B12 and folate)
how does vit B12 absorption occur?
requires binding to intrinsic factor in ileum
how does B9/folate absorption occur?
proton-coupled folate transporter
how are fat-soluble vit digested?
(consumed as esters) hydrolyzed in gut lumen
how are fat-soluble vit absorbed?
uptake via specific transport proteins, re-esterified and packaged into chylomicrons in intes. epi.
where is iron found in body? (3)
majority in Hb, some bound to ferritin, least bound to Mb
why is iron absorption tightly regulated?
so amount taken up = amount lost
What form of iron is found in diet and what form is absorbed?
Ferric/3+; ferrous/2+
What reduces ferric to ferrous iron in intestine brush border?
Ferric reductase
What takes up ferrous iron into enterocytes?
DMT1 (divalent metal transporter 1)
What occurs to ferrous iron once in enterocytes?
Fe2+ is stored and bound to ferritin, remainder ferrous iron transported into circulation
What exports remaining Fe2+ out of enterocytes?
Basolateral transporter ferroportin 1 (FP)
What occurs to ferrous iron once in circulation?
Converted to ferric (Fe3+) and binds to transferrin (transport protein)
What’s the difference between carb, fat and protein absorption in intes. epi?
Carb: secondary active transport->facilitated diffusion
Protein: secondary active transport->facilitated diffusion
Fat: diffusion->exocytosis
How many in 10 adults were considered obese in 2016?
4/10
What occurs if fat absorption is blocked?
Diarrhea (fatty=steatorrhea)
where is the liver located?
under diaphragm and abdominal cavity
what do absorptive segments of the GI tract drain into?
hepatic portal vein
what is the hepatic portal system?
hepatic portal vein drains from GI and supplies liver (substances absorbed in intes. must pass through liver before entering circulation)
where does the liver receive blood from?
aorta and hepatic portal vein (drains into vena cava)
what are the hepatic lobules?
regular, repeating structure of liver with central vein and 6 portal triads (hexagon)
what is the hepatic portal triad?
unit of hepatic lobule with portal vein, hepatic artery and bile duct
what is the function of the portal vein of the portal triad?
percolates blood btwn hepatocytes and empties into central vein (towards center)
what is the function of the hepatic artery of the portal triad?
oxygenates hepatocytes and drains arterial blood into central vein (towards center)
what is the function of the bile duct of the portal triad?
drains bile produced by hepatocytes (towards periphery of hepatic lobule)
what direction does bile and arterial and venous blood flow in hepatic sinusoids?
bile: from hepatocyte to bile duct (outwards)
arterial: artery to CV (inwards)
venous: portal vein to CV (inwards)
what is the functional anatomy of hepatic lobules (how do hepatocytes receive blood)?
gaps btwn endothelial cells (fenestrations) allows blood to flow into space of Disse and come into contact with hepatocytes
what are 3 ways the liver serves its role in whole-body carb metabolism?
- glycogen storage (glycogenesis, glycogenolysis)
- glucose synthesis (gluconeogenesis)
- buffers blood glucose levels (takes up glucose postprandially, secretes it as needed)
what are 4 ways the liver serves its role in whole-body lipid metabolism?
- stores lipids as triglycerides
- energy production (beta-oxidation)
- De novo lipogenesis (lipid formation)
- lipoprotein secretion (TGL as VLDL)
why is lipid storage in the liver problematic?
non-alcoholic fatty liver disease
which enzymes play a role in detoxification in the liver?
cytochrome P450 family (CYPs)
what is the general activity of CYPs?
detoxify xenobiotics and toxins through oxidation
what is the most common rxn catalyzed by CYPs?
mono-oxygenase rxn (incorporation of a hydroxyl group)
what is the general mono-oxidation rxn?
RH + O2 + NADPH + H+ –> ROH + H2O + NADP+
how does mono-oxidation aid detoxyfication?
-OH group makes molecule more polar, water-soluble and easier to secrete
what does CYP2E1 do?
turns ethanol into acetaldehyde (high alcohol consumption)
why is it important not to drink alcohol while on medication?
ex: acetaminophen normally broken down by glucuronidation, but CYP2E1 (high w/ alcohol) will produce a toxic metabolite
why must [ammonia] be tightly regulated?
membrane-permeable and toxic to CNS
how is ammonia generated in the body?
amino acid metabolism
what is ammonia metabolized to in a hepatocyte?
urea
how is ammonia excreted from the body? % as urine and feces?
urea can diffuse into circulation (from liver) and be excreted; 75% urine and 25% feces
the liver can regrow from __% of its original size
25
living liver donor can donate __-__% of their liver
40-60%
what is liver fibrosis?
scar tissue forms on liver
what is liver cirrhosis?
growth of connective tissue destroys liver cells
bile is secreted by hepatocyte into….
bile canaliculi (drains into bile ducts)
what is the enterohepatic circulation? (form)
Circulation of gallbladder/liver secretions into duodenum via common bile duct and reabsorbed in ileum by hepatic portal vein
what causes the yellow-green colour of bile?
bile pigments: bilirubin and biliverdin
what are bilirubin and biliverdin products of?
Hb catabolism from RBC breakdown in liver and spleen
what is bilirubin bound to in circulation?
albumin
what is bilirubin metabolized into in hepatocytes?
bilirubin glucuronide
what is the benefit of converting bilirubin to bilirubin glucuronide?
more water soluble (transported into bile canaliculi for secretion)
what is jaundice?
yellowing of body tissues due to bilirubin accumulation
what are the prehepatic, hepatic and posthepatic origins of jaundice?
pre: incr breakdown of RBCs
hepatic: liver disease (cant metabolize bilirubin)
post: obstruction of bile secretion
what is hyperbilirubinemia?
high levels of bilirubin in circulation and accumulation in CNS (can cause brain damage)
what causes neonatal jaundice?
breakdown of fetal Hb and delayed maturation of metabolic pathways in liver
how is neonatal jaundice treated? why?
phototherapy; blue light catalyzes isomerization of trans- to cis- isomer of bilirubin w/ incr water solubility
how does the stomach not digest itself? (3)
mucus-bicarbonate barrier btwn lumen and epi. cells (alkaline-neutralizes stomach acid), tight junctions btwn epi. cells (no leak of acid into ISS), epi. cell turnover (replace damaged cells)
what does breakdown of the mucus-bicarbonate barrier in the stomach lead to?
erosion of the gastric epi. and ulcers
what was believed to be the cause of ulcers? (historically vs experimental)
Historically: stress
Barry Marshall: infection (Helicobacter pylori)
what % of duodenal vs gastric ulcers are caused by Helicobacter pylori?
duodenal: 90%
gastric: 80
how can stomach ulcers be diagnosed? (4)
medical history/physical exam, test for H. pylori, endoscopy, barium meal + x-ray
how can stomach ulcers be treated? (4)
antibiotics (if H. pylori +), antacid (short term), or inhibit stomach acid production w/ histamine blockers (block receptors on parietal cells) or proton pump inhibitors (inhibits H/K ATPases on parietal cells)
what are 2 types of gallstones?
- cholesterol (85% in developed world)
2. calcium bicarbonate
how do cholesterol stones develop?
[cholesterol] in bile incr until it precipitates out of solution into crystals (as micelles)
what can cause incr biliary [cholesterol]?
incr hepatic secretion of cholesterol or too much ion+water absorption
what are the effects of small vs large gallstones in the gallbladder?
small: easily passed from gallbladder to intes. and excreted
larger: get trapped leaving gallbladder (painful but bile secretion can occur from liver)
what are the effects of large gallstones trapped in the common bile duct? (3)
bile secretion is impaired and decr digestion/absorption of fats (diarrhea) and fat-soluble vitamins
what does backflow of bile cause? (3)
inhibition of its secretion, decr bilirubin excretion and obstructive jaundice
what are the effects of large gallstones trapped in the ampulla of vater? (3)
blocks bile/pancreatic secretions, decr nutrient digestion/absorption and nutritional deficiency
how can gallstones be diagnosed? (3)
medical history/medical exam, ultrasound, CT scan
how can gallstones be treated? (3)
asymptomatic (no treatment), medication to dissolve them (ursodiol-bile salt, helps cholesterol stay dissolved), surgical removal of gallbladder (laparoscopic cholecystectomy)
is it possible to live without the gallbladder? effect?
yes; harder to digest fats
what is colitis?
inflammation of inner lining of colon
what are the symptoms of colitis? (4)
abdominal pain, cramping, diarrhea, others depending on cause
what are 4 causes of colitis?
infection, inflammatory bowel disease (Crohn’s disease or ulcerative colitis), allergic rxn (gluten), ischemia (decr blood supply)
what bacteria causes infectious colitis?
clostridium difficile (C. diff)
what is C. diff?
gram + spore-forming bacteria
is C. diff a constituent of gut microbiome?
yes (vegetative)
in what individuals is C. diff typically found?
neonates, 2-5% of adults (if normal immune response)
what are 2 impacts of C. diff?
leading cause of health-care associated diarrhea and community acquired colitis
what does “health-care associated” disease mean?
nosocomial infection: originated in a hospital (antibiotic exposure)
what is the spectrum of C. diff symptoms if failure to mount immune response? (6)
self-limiting diarrhea, fulminant colitis, pseudomembranous colitis, toxic megacolon, bowel perforation/sepsis and multiple organ failure
what is the life cycle of C. diff in the body?
spores enter through mouth, resistant to gastric acid/digestive enzymes, exposed to E source in sm. intes. (activate spores to bacteria), colonize colon and produce toxins (biofilm formation)
what are the pros and cons of antibiotics to treat C. diff?
pro: effective
cons: antibiotic resistance, broad-spectrum antibiotics can cause recurrent infections (need narrow spectrum)
what is another way to treat colitis? (not antibiotics)
fecal microbiota transplant (FMT)
what is fecal microbiota transplant?
transplant healthy bacteria (from stool) to diseased patient (in pill)
what are the barriers for fecal microbiota transplant? (3)
public acceptance, safety, standardization/identification of bacterial signatures (ensure donor is healthy)
pancreatic acinar cell secretions (4)
pancreatic amylase, pancreatic lipase, chymotrypsin, and trypsinogen
how are pentose sugars absorbed in the sm. intes?
diffusion (ribose)