Water and Ion Absorption

Organ Physiology

Contribution to body electrolyte and fluid balance

Fluid secretion is ~9L/d (can reach 30L/d in diarrhea disease states) – 98 to 99% of fluid is reabsorbed

Exchange occurs between the "transcellular space" and the "extracellular fluid" (plasma and interstitial fluid)

Secretion: fluids from extracellular space Þ intraluminal compartment (transcellular space)

Absorption: fluids from intraluminal compartment Þ the extracellular space

If secretion > reabsorption Þ can severely compromise extracellular space and its electrolyte composition

Regional contributions to fluid and Na+ transport

Na⁺ homeostasis in the GI tract: mEq/d:

Na secretion = Diet (150), saliva (50), gastric juice (40), Bile (150), pancreatic juice (280), intestinal secretion (150) = 820 mEq total

Na reabsorption = Duodenum (20), jejunum (100), ileum (560), and colon (135) = 815 mEq total

Fluid movement across epithelium follows electrolyte flow

General trends:

Amount of electrolyte reabsorbed: jejunum > ileum > proximal colon > distal colon
Transport of electrolytes against their concentration gradient: distal colon and rectum > ileum > jejunum

Consequences of loss of GI fluids

Electrolyte composition of fluids secreted by major exocrine glands into GI tract differs from serum

Loss of specialized GI fluids can affect the body balance of specific electrolytes

Loss of gastric juice (vomiting) Þ loss of HCl (metabolic alkalosis)

Loss of intestinal fluid with stool (diarrhea)

Loss of NaCl Þ decreased plasma and interstitial space

Loss of NaHCO₃ Þ metabolic acidosis

Loss of K⁺ (stool about 25mM K+; plasma only 4mM) Þ hypokalemia

Block of Cl^-/HCO₃^- exchange in ileum and colon (congenital chloridorrhea)

Loss of Cl^- Þ metabolic alkalosis

Functions of small intestine: pH neutralization; equilibration to isotonicity (both occur in upper portions of duodenum)

Cell and Tissue Mechanisms of Electrolyte Transport

Role of tight junctions

2 different transport pathways Þ transcellular (through cell) and paracellular (between cells)

The lower the resistance, the leakier the tight junctions, and the greater the transport of salt and fluid across the epith

When epithelium is "leaky", > 95% of ions move thru paracellular space Þ allows equilibration of Na between plasma and luminal compartments (important in active nutrient absorption (ie glucose absorption) and NaCl secretion)

Small intestine (bulk regulation) epithelium is "leaky" while the colon (fine regulation) is of intermediate resistance

Surface epith (absorption) Þ tight; crypt (Na⁺ secretion) Þ low resistance, "leaky"

Na⁺ absorption (3 mechanisms)

(1) Nurient-dependent (Present in all of small intestine, but not colon)

Examples: Na-dependent glucose and Na-dependent amino acid co-transport
Not down-regulated by secretagogues thus glucose and amino acid containing electrolyte solutions are used for Oral Replacement Solutions (ORS) in patients with severe electrolyte loss due to diarrhea

(2) Electroneutral (Present in all of small intestine and colon; Responsible for bulk of intestinal NaCl absorption)

Can be up and down-regulated (phosphorylation of transporter suspected; still under investigation)

Can be turned off by secretagogues (cholinergic agents, VIP, cholera toxin)

High capacity for isotonic NaCl absorption (luminal NaCl usually does not drop below 70mM)
channel consists of Na/H exchange in parallel with Cl/HCO₃ exchange

NaCl absorption is decreased by inhibitors of carbonic anhydrase (eg acetazolamide)

(3) Electrogenic; (Found mainly in the distal colon in Na depleted states (high serum aldosterone))

Aldosterone induces expression of ENaC (epithelial sodium channel) in the apical memb of epithelum which is sensitive to low concentrations of the diuretic amiloride (- regulator) and mineralcorticoids (+ regulator)

The Na flux generates a transepithelial potential (60mV)

Allows depletion of luminal Na concentration down to 5-10mM Þ highly concentrative, but low capacity

NaCl secretion

Secretory diarrhea results from shift in balance of intestinal electrolyte absorption and secretion

Electrolyte absorption carried out in villus and secretion in crypts

NaCl secretion is energized by the same N,K ATPase in the basolateral memb as absorption

Rate limiting step is a Cl- channel in apical memb (CFTR – cystic fibrosis transmemb regulatory protein) which mediates Cl- efflux from the cell to the lumen down an electrical potential (electrochemical gradient) - (Fig 15)

The potential is maintained by K+ efflux thru K+ channels at the basolateral side
Na+ is secondarily electrophoresed thru the paracellular space into the lumen
NaCl influx is mediated on basolateral side by Na/K/2Cl co-transporter (inhibited by loop diuretics – furosemide)

In Cystic Fibrosis, NaCl secretion is defective due to defect in apical Cl channel Þ lack of NaCl secretion Þ high incidence of meconium ileus disease (obstruction of intestine during passing of first stool of newborn)

CFTR is a cAMP-regulated Cl channel located in crypt cells

Secretagogues turn on the secretory mechanism and turn off the electroneutral NaCl absorption

Bicarbonate transport

actively secreted by the duodenal epithelium and Brunner’s glands (in duodenum)

bicarbonate secretion is accompanied by proton extrusion toward the blood side

In ileum and colon, bicarbonate is secreted in exchange for Cl absorption – Fig 16

Involves a Cl/HCO₃ exchanger in brush border membrane Þ absent in genetic disease chloridorrhea Þ results in Cl- loss and alkalosis (of plasma)

K⁺ transport

mainly passive (possibly thru tight junctions)

Concentrations in upper small intestine are 20 – 30mM (much higher than serum – 4mM) Þ thus no active reabsorption necessary

Colon can actively secrete K⁺ (important when K⁺ excretions by the kidney fails)

Cellular mechanism = K⁺ channel in the luminal memb of epithelial cells Þ allows K⁺ to move down concentration gradient into the lumen

Active K⁺ reabsorption in distal colon (involves H,K-ATPase related to the gastric H,K-ATPase)