HECKdigestion and absorption of fluids and electrolytes Flashcards
Which part of GI absorbs the most
SI
What part of GI ares most electrolytes reabsorbed
Jejunum(all) and then in distal colon (except for K)
What is segmental heterogeneity
differences of cell expression of the transporters along the length of intestines
What is surface herterogeneity
differences in the trasport from top of villus to bottom of crypt
What is cellular heterogeneity
differences in transport mechanisms in different cells within sam villus or crypt
What is the net absorption and net secretion in SI?
Large I?
SI: absorb NaCl and K, secrete HCO3
LI: absorp NaCl, secrete K HCO3
What does it mean by saying epithelial cells in intestine are polar
apical side and basolateral
Mucosal resistnace depends on what type of movement
paracellular Resistance from tight junctions
How does resistance of epithelium change as you move away from mouth, change as you move down crypt?
increases as move away from mouth
increases as move down crypt
What are secretagogues
induce secretion, agonists that also increase second messengers.
What natural substance can act as a laxative
bile acid
What are absorptagogoues
Induce absorption (neural, endocrine and paracrine)
What are types of absorptagogues
mineralcorticoids, glucocorticoids, somatostatin and Norepinephrine
What is osmotic diarrhea
dietary component that is pulling H2O into the lumen because it is not being absorbed
What is Secretory diarrhea
secretion of fluid and electrolytes from intestine induced by secretagogues
What are secretagogues from bacteria
enterotoxins that increase second messengers
does not affect Na absorption
What will reverse secretory diarrhea
Na and Glucose solution
Where is most of Na absorbed
villous epithelium of SI
surface epithelium of LI
Describe the Na, K ATPase
low intracell Na because pumping into interstitial
gradient then used as driving force
What are the 4 types of apical Na transport
Nutrient-coupled
Na/H exchanger
Electroneutral NaCl absorption
Electrogenic Na absorption
Describe path and energy for nutrient coupled Na transport
secondary active transport running on Na gradient
transports 1 Na in along with glucose or glactose
What is significant about the nutrient-coupled Na transport that is not like the other
not inhibited by cAMP of gAMP
so can still work in cholera or E coli enterotoxin from bacteria which increase cAMP
What is the name of the glucose.Na cotransporter
SGLT1
What is the other type of Nutrient coupled Na transport
Na/aa co-transport
Describe the mech of Na/H exchanger
couples Na uptake to H extrusion into intestinal lumen
stimulated by secretion of HCO3 in duodenum
driven by Na gradient
Where in the intestine are the Na/H exchanger
throughout intestine, mainly jejunum
What is the effect on pH from Na/pH
increase intracell pH
decrease luminal pH
What would pancreatitis have as an effect on NaH exchanger
wouldnt run because needs HCO3 to stimulate. so luminal pH would not decrease
In the proximal small intestine why is there the Na/H exchanger without Cl-HCO3
runs on HCO3 alone
Describe the mech of the electroneutral NaCl absorption
Na-H and Cl-HCO3 apical membrane coupled through pH neutrality
Where and when is the electroneutral NaCl absorption most important
ileum and large intestine, primary method of Na absorption between meals
Describe the effects of travelers diarrhea on the electroneutral NaCl
inhibited NaCl absorption because of increased cAMP and cGMP because of increased Ca
describe mech of electrogenic Na absorption
epithelial Na channels on apical surface
depends on gradient from NaK pump
Where are the electrogenic Na absorption channels very important
in the distal colon because is a rescue mechanism for Na conservation
What enhances the electrogenic Na absorption
aldosterone(absorptagogue)
Describe chloride absorption
passive voltage dependent
neg lumen charge from Na leaving causes Cl to enter cell paracellularly
Descirbe the active transport of Cl
Cl-HCO3 exchanger, does not run with Na/H pump
where are the Cl-HCO3 exchangers present
surface epithelium of large intestin, villous cells on the ileum
What is the other name for the Cl-HCO3 exchanger and why
DRA exchanger because down regulated with adenomas (colon cancers)
How does Cl cross the basolateral side
ClC-2 voltage gated
What causes congenital Cl diarrhea
absence of Cl-HCO3
How is absence of DRA specific to colon
the gene is different for Cl exchangers in RBC and renal tubules
What are signs of congenital Cl diarrhea
extremely high [ ] Cl in stool
high plasma [ ] HCO3 (alkalotic)
Describe Cl secretion mechanism
requires activation by secretagogues
the NaK pump drives the NaKCl pump to increase intracell Cl levels
What is the importance of leaky K channels on apical side
needed so that K [ ] in the cell does not get too hight with the NaKCl and NaK pumps
What is the name of the main Cl channel on apical side
CFTR
Where does K absorption take place
small intestine and distal colon
how does K get absorbed in small intestine
paracellular, passive transport, pulled through tight junctions with movement of water
how does K get absorbed in distal colon
active transport transcellularly
apical H/K pump which pumps H into lumen
basolateral NaK pump
Where does K secretion take place
only in the large intestine
Describe passive K secretion
predominant route
driven by negative lumen
paracellular
What increases the passive secretion of K
dehydration because aldosterone is secreted so Na absorbed so Cl leaves lumen making it more negative and then passive K secretion
high levels of K in stool when dehydrated
Describe active K secretion
throughout colon, activated by aldosterone and cAMP
pump/leak so the drive is from the NaK and NaClK pump
Describe the active Ca absorption
only in duodenum, speed of flow reduceds uptake
active transcellular and under the control of vitamin D
Why is vitamin D needed for ca uptake
because Ca is potent second messenger needs to be bound to Calbindin
Vit D induces synthesis of Calbindin
Before Ca-Calbinding cross the basolateral side what must happen
separate and then Ca leaves via Na Ca exchanger
Describe the passive Ca absorption
paracellular
depends on [ ] in interstitium (which reflects plasma levels)
Where does passive Ca absorption take place and is Vit D needed
not influenced by vit D
talkes place throughout SI (jejunum and ileum)
What natural process enhances passive Ca absorption
lactation
Describe the active uptake of Mg
only in ileum
Independent of vit D and Ca- mech not known
describe the passive uptake of Mg
paracellular throughout duodenum and jejunum
based on Mg [ ]
What is Mg [ ] necessary for
Parathyroid hormone
Whcih form of iron precipitaes more
ferric Fe3+
which form does iron have to be to be taken up by cells
Ferrous Fe2+
Where does most of our Fe2+ come from
Vit C, asorbic acid reduces Fe3+ to Fe2+ and thus increases absorption
What 2 major pathologies arise from iron dysregulation
anemia (depletion)
hemochromatosis (iron overload)
Why are women less susceptible to hereditary hemochromatosis
because during menstruation release excess Fe so it does not build up
What can excess iron result in
cirrhosis, hepatomas, pancreatic damage, bronze pigmentation, pituitary and gonadal failure, arthritis, cardiomyopathy
How do we detect iron dysregulation
elevated iron and transferrin saturation, elevated ferritin, liver biopsy
What is the Tx for iron dysregulation
phlebotomize, blood letting every few months to normalize levels
What are the two forms of iron
heme iron and nonheme
what type of iron is absorbed more efficiently heme or nonheme
heme
how is heme iron absorbed
active transcellular transport in duodenum
binds brush border protein then transported to cytoplasm via endocytotic mech
What cleaves heme and Fe3+
heme oxygenase
What cell reduces Fe3+
enterocyte
How is nonheme absorbed
active transcell transport in duodenum
What is the Iron transporter on apical side
divalent metal transporter DMT1
cotransports Fe2+ and H (not specific for iron)
Which tranporter is responsible for lead poisoning
the DMT1
What is the name of the reducer for ferric and what is important about its location
Ferric reductase Dcytb
located on apical extracell surface because has to reduce Fe3+ before can be taken up by DMT1
What protein carries Fe to the basolateral membrane
mobilferrin
What is the transporter for Fe on the basolateral side
Ferroportin transporter FP1
When is Fe2+ oxidized
when reaches the intersitial fluid.
Why must Fe2+ be oxidized in interstitium
transferrin can then carry it to the plasma
how is Fe3+ stored
bound to transferrin and stored in liver and reticuloendothelial system
Diarrhea from cholera has what appearance
rice water from the mucous
What is unique about diarrhea from E coli
has blood in it
cAMP has what affect on CFTP
phosphorylates it