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Digestion/Absorption: Fluids & Electrolytes (K Absorption &…
Digestion/Absorption: Fluids & Electrolytes
Na Absorption
most absorbed by villous epi (SI) & surface epi (LI)
Na,K-ATPase
Na across
basolateral membrane
>> low intra[Na]
[gradient] = driving force
mediates ALL transcellular transport
apical transport (4)
nutrient-coupled
secondary active >> inc. intra[Na] >> Na pumped
electrogenic process >> lumen (-) >> Cl driving force
inhibition
ONLY one not inhibited by cAMP or cAMP agonists (i.e. E.coli or cholera enterotoxin do not affect)
Na/glucose cotransporter SGLT1
Na/amino acid cotransporters
(class specific)
primary post-meal absorption
thru-out SI; solely in villous epi cells (not crypts)
Na-H exchanger (NHE3)
inc. intra-pH; dec. lumen-pH
stimuli: HCO3 secretion in duo, pancreas & bile
thru-out intestine
in prox. SI w/o Cl-HCO3 exchanger >> [HCO3] stimulus alone
several isoforms
basolateral: maintain intra-pH
apical: trans-epi Na movement
inhibition:
amiloride
diuretic
electroneutral NaCl absorption (NHE3)
parallel Na-H & Cl-HCO3 exchangers
primary method b/w meals
ileum & thru-out LI
inhibition:
cAMP & cGMP
inc. intra[Ca]
clinical:
dec. NaCl abs. >> important in pathogenesis of diarrhea
E.coli induced traveler's diarrhea (+) cAMP
electrogenic Na absorption (ENaC)
highly specific
very distal colon
enhanced by aldosterone
opening of channels
translocation of channels to apical surface
expression of channel
inhibition:
amiloride
diuretic
electrogenic process >> lumen (-) >> Cl driving force
Na abs against large gradients (Na conservation)
Cl Absorption & Secretion
voltage-dependent
driven by either:
nutrient-coupled Na abs. in SI (electrogenic & paracellular)
electrogenic Na abs in distal colon
passive
Cl-HCO3 exchanger
active
villous cells of ileum & surface epi of LI
DRA exchanger
: "down-regulated in adenoma"
CIC-2 may be involved in basolateral transport
congenital Cl diarrhea
absence of Cl-HCO3 exchanger
extremely high [Cl] in stool
high plasma [HCO3] >> alkalotic
Cl-exchangers in blood cells & renal tubes unaffected
Tx: salt replacement, oral rehydration, butyrate
parallel transport w/ Na-H exchanger in ileum & proximal colon (
electroneutral NaCl absorption
)
secretion
promotes Na secretion >> NaCl secretion
dec. NaCl abs. >> important in pathogenesis of diarrhea
requires activation by secretagogues (basal state ~0)
requires 3 basolateral transporters:
Na-K pump = driving force for...
Na/K/Cl contransporter
>> inc. intra[Cl] >> secretion
K channels (recycling)
apical
cystic fibrosis transmembrane regulator (CFTR)
mainly in crypts
K Absorption & Secretion
dietary intake = 80-120 mmol/day
output in stool = 10 mmol/day (up to >100 mM)
absorption
solvent drag
passive
paracelluar via movement of H2O
in SI
active
only in distal colon
transcellular
K homeostasis
apical:
H-K pump
(H+ into lumen)
basolateral:
Na-K pump
usually dietary depletion will enhance abs.
secretion
passive
predominant route
paracellular d/t (-) lumen (-15 to -25mV)
most in distal colon
dehydration >> aldosterone secretion >> (-) lumen
active
thru-out colon
basally low
stimuli: aldosterone & cAMP
pump-leak model
basolateral
Na/K pump = driving force for...
Na/K/Cl contransporter
>> inc. intra[K] >> secretion
K channel
for K recycling
apical:
K channel
Calcium Absorption
Ca
found in SI (diet & digestive secretions)
most in diet from dairy (some in greens not absorbed bc oxalate-bound)
absorbed = 500mg/day
secreted = 325 mg/day
net update = 175mg/day
Ca abs. declines w/ age
active
only in duo
transcellular
villous epi cells controlled by Vit. D
all steps
(+) Calbindin synthesis
process
1.
Ca channels
driven by gradient >> inc. intra[Ca]
Ca binds to calbindin
3.
Ca pumps
&
Na-Ca exchangers
on basolateral membrane >> inc. [Ca] in interstitial fluid
passive
paracellular
higher [ ] than active
not controlled by Vit. D
thru-out SI (jejunum & ileum)
enhanced by:
low [plasma]
pregnancy & lactaction
Iron Absorption
exists as
ferrous (Fe2+)
insoluble at pH>8
ferric (Fe3+)
not readily abs.
insoluble at pH>3
forms salt complexes w/ anions
complexes w/
ascorbic acid (Vit C)
>> reduces ferric to ferrous >> Inc. abs.
complexes w/
tannins
found in tea >> dec. solubility & abs.
hemes
O2-carrying =
hemoglobin
&
myoglobin
e-carrying =
cytochromes
anemia
: iron depletion
hemochromatosis
: iron overload
Hereditary Hemochromatosis (HH)
abs. XS iron >> toxic to liver
autosomal recessive
HFE gene - related to MHC; fxn unknown, possibly hepcidin regulation
homozygotes in mid-30s
women less affected d/t menstruation
results in:
cirrhosis
hepatomas
pancreatic damage
bronze pigmentation
pituitary & gonadal failure
arthritis
cardiomyopathy
detection:
elevated iron & trasnferrin sat.
elevated ferritin
liver biopsy
Tx: phlebotomize every few mo.
builds up in Kupffer cells
Fe
found in SI (diet)
low absorp. overall (10-20% ingested); coupled to Fe stores
meat primarily; some vegs
men: 10 mg/day; women: 15 mg/day
no excretion; min. loss except d/t menstruation
2 forms
heme Fe
abs. more efficiently
enters cells by either:
endocytotic mechanism
to cytoplasm
heme oxygenase
: releases free Fe3+, CO & biliverdin
enterocyte:
biliverdin >> bilirubin >> bile
Fe3+ >> Fe2+ = free iron
binding brush border protein
derived from myoglobin & hemoglobin
non-heme Fe
abs. less efficiently
divalent metal transporter (DMT1)
cotransports Fe2+ & H+ (inward directed H-gradient)
not specific (including toxic Cd2+, Pb2+; not Fe3+)
hepcidin
down-regulates DMT1 & Fe abs.
from Kupffer's cells
regulates other Fe respons. pathways
stimulated by IL-6 (inflammation) >> anemia
ferric reductase (Dcytb)
Fe3+ >> Fe2+
apical EC surface
required for uptake by DMT1
mobilferrin
binds Fe2+ in cytoplasm >> carries to basolateral mem.
ferroportin transporter (FP1)
Fe2+ across basolateral mem.
expression is Fe-responsive (5' UTR) >> binding dec. protein synthesis
ferric or ferrous form
ONLY active transcellular transport
in duo (enterocytes)
Fe2+ reaches I.F. where:
ferroxidase hephaestin
oxidizes Fe2+ >> Fe3+
Fe3+ binds transferrin >> carried thru plasma
binds apoferritin >> ferritin >> stored in liver & RES