Digestion and absorption of fluids and electrolytes Flashcards
Net ion movement
Difference between movement:
From lumen into blood
From blood into lumen
Segmental heterogeneity
differences in transport along the length of the intestines
Surface heterogeneity
differences in transport from the top of a villus to bottom of a crypt
cellular heterogeneity
differences in transport mechanisms in different cells within the same villus/ crypt
Small intestine absorption and secretion
net absorption of Na, Cl, and K
net secretion of HCO-3
Large intestine absorption and secretion
Net absorption of Na and Cl
Net secretion of K and HCO-3
Intestinal epithelial cells are polar
contain an apical and basolateral surfaces
transcellular movement
solute crosses two membranes in series
Paracellular movement
solute moves passively between epithelial cells through tight junctions
mucosal resistance is dependent on paracellular resistance which is a function of tight junction permeability and depends on tight junction structure
Overall, resistance increases as you move away from the mouth
Overall, resistance increases as you move down the crypt
resistance changes in paracellular movement
Overall, resistance increases as you move away from the mouth
Overall, resistance increases as you move down the crypt
actions and examples of secretagogues
Induce secretion Agonists Increase second messengers Bacterial toxins Hormones and Neurotransmitters Immune regulatory products Laxatives Bile acids
actions and examples of absorptagogues
Induce absorption neural, endocrine or paracrine factors few agonists Mineralocorticoids Glucocorticoids Somatostatin Norepinephrine
Osmotic diarrhea
Osmotic Diarrhea
Dietary component that is not absorbed
Ex. lactose intolerance
Secretory diarrhea
Secretion of fluid and electrolytes from the intestine
Induced by secretagogues
Enterotoxins from bacteria
Increase second messengers
Does not affect Na+ absorption, therefore, administration of Oral Rehydration Solution, enriched with Na+ and Glucose reverses secretory diarrhea
Sodium absorption
Most absorbed by:
Villous epithelium of small intestine
Surface epithelium of large intestine
Na,K-ATPase (pump)
All transcellular Na+ transport is mediated by this pump which moves Na+ across the basolateral membrane
Results in low intracellular Na+ concentrations
Gradient used as a driving force for Na+ entry and other molecules through the gradient, Na+ channels or coupled channels
Nutrient-coupled Na+ transport
Secondary active transport
Couples uphill movement of nutrients with downhill (energetically favorable) movement of Na+
Increases intracellular [Na+] which thereby increases Na+ being pumped across the basolateral membrane into blood
Electrogenic process
Makes lumen more negative which can be driving force for Cl-
Only type of Na+ transport not inhibited by cAMP or cAMP agonists
I.e. No Inhibition by E. coli or cholera enterotoxin
Glucose coupled Na+ transport
Na/glucose cotransporter SGLT1
Apical membrane transport
Amino acid coupled Na+ transport
Na/amino acid cotransporters
Apical membrane transport
Each specific for different classes of amino acids
What is the only type of Na transport not inhibited by cAMP or cAMP agonists?
nutrient-coupled
Na-H Exchanger (NHE3)
Couples Na+ uptake to proton (H+) extrusion into intestinal lumen
Increases intracellular pH
Decreases luminal pH
Stimulated by secretion of HCO-3 in the duodenum, pancreas and bile
Driven by intracellular [Na+]
Present throughout intestine
Present in proximal small intestine without Cl-HCO3 exchanger
Stimulated by [HCO-3] here alone
Electroneutral NaCl Absorption (NHE3)
Parallel apical membrane exchangers coupled through pH
- Na-H
- Cl-HCO3
Primary method of Na absorption between meals
Does not contribute to post meal absorption (nutrient coupled)
Ileum and throughout large intestine
Clinical relevance of NHE3:
Decreasing NaCl absorption important in pathogenesis of diarrhea
E. coli induced traveler’s diarrhea activates cAMP
Inhibited by
cAMP and cGMP
increasing intracellular calcium
Electrogenic Na Absorption (ENaC)
Epithelial Na+ channels on apical surface
Highly specific
Very distal colon where Na+ can be absorbed against large gradients
Important in Na+ conservation
Enhanced by aldosterone
Just like kidneys, an aldosterone responsive epithelial tissue
Dependent upon gradient created by Na-K pump on basolateral surface
Chloride absorption is often coupled to
Often coupled to Na+ absorption through intracellular gradient
Passive transport of chloride
Voltage dependent Cl- absorption
Cl- absorption is driven by either
Nutrient coupled Na+ absorption in the small intestine
Creates a lumen negative potential difference
Paracellular
Electrogenic Na+ absorption in the distal colon
Creates lumen negative potential difference
Remember: Both are dependent on Na-K pumps in the basolateral membrane.
Active transport of chloride: CL-HCO3 Exchanger (DRA)
Apical surface One Cl- brought in from lumen and one HCO3- extruded from cell Villous cells of ileum Surface epithelium of large intestine DRA Exchanger Down-regulated in adenoma Congenital Cl- Diarrhea
Congenital Cl- diarrhea
absence of Cl-HCO3 extremely high [Cl-] in stool high plasma [HCO3-] Alkalotic Cl- exchangers in blood cells and renal tubules unaffected ( different gene)
Chloride secretion (CFTR)
Promotes Na+ secretion resulting in NaCl secretion
Important in the pathogenesis of diarrhea
Basal state of secretion is low or 0
Requires activation by secretagogues (Ca2+ or cAMP)
Requires 3 basolateral membrane transporters
Na-K pump
lowers intracellular [Na+]
driving force for Cl- entering through Na/K/Cl cotransporter
Na/K/Cl cotransporter
Increases intracellular [Cl-]
K+ channels
Apical membrane
Cystic fibrosis transmembrane regulator (CFTR)
Cl- channel
K+ absorption happens where?
small intestine
K+ passive transport
Solvent Drag
Paracellular
Pulled through tight junctions via the movement of water
K+ Active transport
only in distal colon Transcellular K+ homeostasis Apical H-K pump Pumps H+ into lumen Basolateral Na-K pump
K+ secretion happens where?
large intestine
Passive K+ secretion
Passive K+ Secretion Predominant route Driven by negative lumen (-15 to -25 mV) Paracellular Most in distal colon Dehydration Results in aldosterone secretion makes lumen negative (Na+ absorption) inducing passive K+ secretion
Active K+ Secretion
Throughout colon Basally low Activated by aldosterone and cAMP Pump-leak model Basolateral membrane Na/K pump Creates low intracellular [Na+] which drives the cotransporter Na/K/Cl cotransporter Brings in K+ for secretion and Na+ to drive pump K+ Channel Contributes to K+ recycling Apical membrane K+ Channel
Calcium absorption: active
transcellular
Only in duodenum
Small surface area and high speed of flow reduces uptake
Villous Epithelial Cells
Under control of Vitamin D (Influences all steps, Induces synthesis of Calbindin)
Process of calcium active absorption
1) Uptake through Ca2+ Channels Moves across apical membrane Driven by the electrochemical gradient 2) Binding to Calbindin Intracellular, cytosolic protein which buffers Ca2+ 3) Extrusion through Ca2+ Pumps and Na-Ca Exchanger Moves across basolateral membrane Into interstitial fluid
Passive paracellular uptake of calcium absorption
Higher concentration than active uptake Not under the influence of Vitamin D Throughout small intestine Jejunum and Ileum Enhanced by low plasma concentration Lactation
Iron exists as
Ferric (Fe3+)
Ferrous (Fe2+)
Vitamin C
Ascorbic Acid (Vitamin C)
- Complexes with Iron
- Reduces Iron from ferric to ferrous
- Increases absorption
note: vitamin c needs to be in the GI tract at the same time as the iron in order to be able to do this
Iron dysregulation
Results in: Anemia Iron depletion Hemochromatosis Iron overload Hereditary Hemochromatosis (HH) Body absorbs excess iron Women less susceptible to damage due to menstruation
Excess iron becoming toxic in liver
Results in: Cirrhosis Hepatomas Pancreatic Damage Bronze pigmentation Pituitary and Gonadal failure Arthritis Cardiomyopathy
Detection:
Elevated iron and transferrin saturation
Elevated ferritin
Liver biopsy
Treatment:
Remove blood from patient (phlebotomize) every few months to normalize iron and ferritin.
Heme Iron
Absorbed more efficiently
Active Transcellular Transport Only:
- Occurs only in duodenum
- Binds brush border protein
- Endocytotic mechanism
Transported to cytoplasm
Heme oxygenase
Releases free Fe3+
Enterocyte reduces Fe3+ to Fe2+
Then handled the same as free iron (see below
Nonheme Iron
- Absorbed less efficiently
Exists as either ferric or ferrous iron
-Active Transcellular Transport Only
Occurs only in duodenum
Active transcellular iron transport: divalent metal transporter
Cotransports Fe2+ and H+ into cytoplasm Inward directed H+ gradient Not specific for Iron Many divalent metals including toxic (Cd2+, Pb2+) Not Ferric iron Ferric Reductase Dcytb Reduces ferric iron to ferrous iron Cytochrome Apical extracellular surface Required for uptake in DMT1
Active transcellular iron transport: mobilferrin
binds Fe2+ in cytoplasm
Carries Fe2+ to the basolateral membrane
Ferroportin transporter (FP1)
Translocates Fe2+ across basolateral membrane
When Fe2+ reachs the interstitial fluid:
oxidized Fe2+ to Fe3+
Facilitates binding to
Transferrin
Carries through plasma
When Fe3+ reaches the blood
Bound to transferrin
Stored in liver and reticuloendothelial system
which ions are affectors of diarrhea
Na and Cl-
Cholera mechanism of action
Cholera toxin binds apical receptors on crypt cells. Results in an increase of cAMP Results in secretion of Cl- by CFTR Na2+ and H2O follow Cl- into lumen Na2+ absorption inhibited by cAMP Result: Secretory Diarrhea
Oral rehydration solution
on the fact that nutrient coupled-Na2+ absorption is not inhibited by cAMP stimulating secretagogues.
Therefore, increasing glucose and/or amino acid concentrations in the lumen increases Na2+ reuptake.
This increases intracellular [Na+] which is necessary for Na,K-ATPase function.
Na,K-ATPase function is necessary for K+ and Cl- absorption as well.
Solution contains varying concentrations of glucose, Na2+, Cl- and HCO3-
Reverses dehydration and metabolic acidosis which were significant causes of mortality in the past.
Direct result of research in nutrient coupled-Na2+ absorption.
