Exopancreatic, Intestinal, Liver Secretions - Fan 2/22/16 Flashcards
pancreatic secretions
1500 mL/day
fx
-
acinar cells: produce digestive enzymes for digestion of all macronutrient
- enzymes typically produced in excess ⇒ amt of digestion is actually limited by gastric emptying
- most of these enzymes are secreted as inactive zymogens, need trypsin to activate (…stymied by secretion of trypsin inhibitor)
-
ductular cells: produce HCO3-rich fluid
- fluid transports enzymes to duodenum, establishes pH ideal for enzyme function
- protects cells via H neutralizatoin
dumping syndrome
conseq of widened pyloric sphincter: everything gets dumped into duodenum
symptoms
- GI: watery, painless diarrhea; gassy
- systemic: weakness, diaphoresis, tachycardia
how? pathophysiology
- carb/protein digesting enzymes in duodenum go to work on everything dumped → sudden increase in osmotic pressure pulls a ton of water into GI lumen
- distention of lumen : watery diarrhea
- bacterial fermentation of nutrients : gas
- loss of blood volume (bc all of water that was pulled into GI tract) : weakness, tachycardia
- loss of blood volume → “hyperglycemia” → insulin oversecretion → reactive hypoglycemia : diaphoresis, tachycardia
majority of pancreatic enzymes are secreted as zymogens
how are they activated?
require trypsinogen → trypsin
via enterokinase (brush border in duodenum)
- if zymogens are activated early/in pancreas…pancreatitis.
- reason why you have trypsin inhibitor
pancreatitis
results from early maturation of pancreatic trypsinogen into trypsin
- congenital trypsin inhibitor deficiency
- abdominal trauma: injured pancreas cells release protease that ends up accidentally activating trypsin
why shouldnt you feed a newborn adult food?
exopancreas is only partially developed at birth…don’t have the amylases and proteases needed to digest!
ionic properties of pancreatic juice
- pH increases at higher secretion rates
- [bicarb] inversely proportional to [Cl]
- [Na} and [K] same as anywhere else
ductular fluid secretion: resting condition
basal secretion state, mechanisms
- serosal side: H/K exchanging ATPase (proton pump) pushes H out of cell → H combines with bicarb → carbonic acid, which dissociates → water + CO2
- CO2 diffuses into cell, combines with H2O → carbonic acid → H and HCO3
- HCO3 pumped out of cell into lumen via HCO3/Cl exchanger
- i.e. [bicarb] inversely prop to [Cl]!
- jx between cells are loose enough to allow Na and K to move from serosal side to lumen
- Cl moves into lumen via Cl channel CFTR (cystic fibrosis transmembrane conductance regulator)
ductular fluid secretion: response to feeding
H stimulates secretion of secretin
- stimulates CFTR - gets it open, longer
- provides gradient for more bicarb secretion into lumen
- stimulates translocation of H/K ATPase into basolateral membrane via cAMP
CCK and Ach supplement action of secretion via basolateral K channel via Ca
- increased K efflux means negative cell environment → more HCO3 and Cl pushed out
control of pancreatic secretion
- phases
- % of secretion occuring in phase
- main mediators
interdigestive : 10%
- motilin?
cephalic : 10%
- vagal
gastric : 10%
- vagal
intestinal : 70%
- CCK: acinar cell enzyme secretion for fat/protein/carb breakdown (in small intestine, once activated by trysin)
- vagal
-
secretin (H): generates lots of bicarb
- potentiated by CCK and Ach/vagal action
intestinal secretion
1500 mL/day
- mainly mucus, other fluids
fx
- protection (bicarb-rich)
- maintenance of luminal isotonicity
- aiding digestion/abs
active secretions from small intestine
- HCO3/Cl exchanger in duodenum only
- both prox and distal intestine have CFTR Cl pump → Cl into lumen, Na follows, water follows ions
duodenum
- apical: DRA/AE1 (HCO3/Cl exchanger), CFTR
- basolateral: NHE (Na-H exchanger), NBC (Na-bicarb cotransporter), Na/K ATPase
jejunum/ileum
- apical: CFTR
- basolateral: NKCC1 (Na, K, 2Cl transporter), Na/K ATPase
mediation of CFTR activity: normal
CFTR activated by PKA-mediated phosphorylation
- presence of H → secretin secretion → adenylate cyclase activity
- ATP → cAMP
- cAMP activates PKA
- PKA phosphorylates CFTR and ramps up its activity
mediation of CFTR activity: pathological state
enterotoxins act as cyclases: go ahead and convert all available ATP to cAMP
- effective constitutive activation of PKA-dep activation of CFTR
- Cl pumped out like crazy, Na follows, water follows ions
- diarrhea, dehydration
external fluid circuit (of intestine)
normal state, disease state
normally, at basal portion of intestinal crypt…
- secretion of Cl, Na, water
at apical portion of int crypt (the tip)…
- mature enterocytes do not have CFTR, and so don’t secrete - absorb instead!!!
- maintain a balance (basal cell secretion ~ apical cell reabs)
in disease state (cholera, other toxins)…
- excess basal secretion via constitutively activated CFTR in basal cells : exceeds capacity of apical cells to reabs
treatment for diarrhea/dehydration due to excess secretion
excess secretion of Cl (followed by Na followed by water) by int crypt basal cells (overactive CFTR) : overwhelms apical cells capacity to reabs
- treat with glucose and NaCl!!!
- will spur SGLT (sodium glucose cotransporter) into action : pull in Na and glucose
- passive reabs of Cl, water (follow Na, glucose!)
- will spur SGLT (sodium glucose cotransporter) into action : pull in Na and glucose
- want to hit pt with equal amt of Na and glucose so as to let SGLT do its 1:1 reabs
- has dramatically reduced deaths due to diarrheal dehydration
