Secretions of the Intestines/Ion Transport Flashcards
Brunner’s Glands
- Brunner’s glands are small glands found in the proximal duodenum close to the pyloric sphincter that secrete mucus and HCO3 - .
- Secretions from these glands are important for protecting the proximal duodenum from acid loads in chyme moving out of the stomach prior to the Sphincter of Oddi where pancreatic secretions emerge.
Intestinal Villi
•Intestinal Villi refers to the extensive foldings observed in the surface of the small intestine. The villi are covered by a layer of epithelial cells with only a few other cell types interspersed (ex. Immune M-cells, endocrine cells). This folding arrangement dramatically increases surface area providing an optimal situation for absorption.
Crypts of Lieberkuhns
- Crypts of Lieberkuhn are extensive pits found between villi at their base, which extend to the submucosa and are found in all parts of the intestine.
- The crypts contain pluri-potential cells, which can differentiate into absorptive epithelial cells as they migrate towards the villus tip. In addition to these precursor cells, a large variety of mucus secreting goblet cells, and endocrine cells are found in the crypts.
- Many of the nutrient sensing endocrine secreting cells are located in the crypts.
Cell Growth and Differentiation
- Stem cells are located in the crypts. Epithelial cell turnover at the tip of a villus is high (3-6 day cycle), so a significant rate of migration of cells from the crypts is necessary to replace lost cells.
- As cells move from the crypts, changes in cell function occur: the absorptive capacity and the level of brush border enzymes both increase dramatically. Therefore, any process that increases cell death at the tip or slows differentiation in the crypts will reduce absorptive capacity and may lead to diarrhea due to malabsorption.
- Since mucosal stem cells divide rapidly, interventions that alter the cell cycle can lead to absorptive abnormalities.
- It is important to recognize that CCK is a primary stimulator of cell differentiation and turnover thereby promoting epithelial recovery.
Water Secretion in the Small and Large Intestine
- Continuous secretion of water is observed from the crypts of both the small and large intestine. Since the area of the small intestine is far great than the colon, the bulk amount of fluid secretion is from small intestine crypts.
- The mechanism for active water secretion depends on activation of a cAMP activated Cl- channel (CFTR).
- VIP is the enteric neurotransmitter that ‘normally’ activates water secretion by elevating cAMP within colonic and small intestinal crypts.
- Inflammation or introduction of noxious compounds into the intestine also may cause elevation of cAMP within crypt cells due to local histamine release (from immune cells) which elicits an acute secretory response promoting flushing of the crypt.
- Similarly, enterotoxins released by infiltrating bacteria such as cholera can cause profound diarrhea via direct activation of adenylyl cyclase or other components of the cAMP signaling pathway
[…] is the enteric neurotransmitter that ‘normally’ activates water secretion by elevating cAMP within colonic and small intestinal crypts.
VIP is the enteric neurotransmitter that ‘normally’ activates water secretion by elevating cAMP within colonic and small intestinal crypts.
Inflammation or introduction of noxious compounds into the intestine also may cause elevation of cAMP within crypt cells due to local […] release (from immune cells) which elicits an acute secretory response promoting flushing of the crypt.
Inflammation or introduction of noxious compounds into the intestine also may cause elevation of cAMP within crypt cells due to local histamine release (from immune cells) which elicits an acute secretory response promoting flushing of the crypt.
Similarly, enterotoxins released by infiltrating bacteria such as cholera can cause profound diarrhea via direct activation of […] or other components of the […] signaling pathway. Mucus secreting Goblet cells also are found throughout the intestine
Similarly, enterotoxins released by infiltrating bacteria such as cholera can cause profound diarrhea via direct activation of adenylyl cyclase or other components of the cAMP signaling pathway.
Mucus secreting […] also are found throughout the intestine.
Mucus secreting Goblet cells also are found throughout the intestine.
[…] are present but less extensive in the colon.
Crypts are present but less extensive in the colon.
•In the colon, crypts contain more goblet cells and stem cells than the small intestine, whereas fewer endocrine cells are observed. Mucus represents the largest component of colonic secretions acting to protect the colon wall and cause fecal material to adhere together.
Normally there is net water […] together with […] secretion to the lumen in exchange for Cl- .
Normally there is net water absorption together with HCO3 - secretion to the lumen in exchange for Cl- .
•Simultaneously, a low rate of water secretion at an alkaline pH protects the colon walls from acid produced by bacteria.
Absorption of Ions and Water
- Water movement follows the movement of osmolytes including ions and nutrients.
- In general, there is net fluid secretion from cells located within intestinal crypts, while there is net fluid absorption by enterocytes lining the villi.
- The surface area of the villi is massive compared to the crypts such that net water absorption is normally favored.
- However, continuous secretion of water, and therefore osmolytes is required to maintain the intestine moist particularly during fasting/resting (inter-digestive) periods.
Sodium Absorption
- Na+ is absorbed along the entire intestine with most absorbed in the jejunum (~80%). Na+ moves into epithelial cells from the lumen through the apical membrane (down its electrochemical gradient) by co-transport with nutrients (small intestine), via Na+ /H+ exchange (primarily proximal intestine) or through Na+ channels (primarily in colon).
- Na+ absorption is dependent on the Na+ gradient generated by the basolateral Na-K ATPase that actively transports it across the basolateral membrane to the interstitial space.
- Since there is net movement of positive charge from the lumen to the blood (3 Na+ to blood for 2 K+ into cell), the lumen is more negative with respect to the interstitial space (15-25 mV). H2O follows NaCl down the osmotic gradient toward blood, therefore H2O movement is critically linked to Na+ absorption.
Chloride Absorption
•The absorption of Cl- is passive in the proximal intestine where junctions between cells are leaky.
-In the jejunum, Cl- moves passively via paracellular pathways to offset net positive charge movement caused by rapid Na+ absorption.
•However, as the epithelia become less leaky in the distal intestine, electroneutral Cl- transport across the lumenal membrane becomes important for its absorption to the blood.
- In the ileum and colon, uptake of Cl- across the lumen membrane occurs through Cl/HCO3 - coupled antiport, which also provides for buffering bacterial H+ production.
- Carbonic anhydrase has been found in colonic enterocytes, and is likely important in facilitating HCO3 - production, and thereby a favorable chemical gradient for HCO3 movement to the lumen coupled to Cl- absorption into the cells.
Na+ Channels
•most important in distal colon
Na+ - Substrate Transporters
•decreases from proximal intestine to ileum
Na+/H+
•high is proximal intestine, low in colon
Aldosterone
•Increases number of Na+ channels and NKA and thus increases Na+ absorption which is particularly important for regulating water absorption in the colon.
Cl- Absorption
- paracellular in the proximal intestine
- Cl-/HCO3 - in the distal intestine/colon
The largest fraction of Na+ is absorbed into the […] through Na+ - coupled co-transporters.
The largest fraction of Na+ is absorbed into the small intestine villus enterocytes through Na+ - coupled co-transporters.
•The Na-K ATPase removes this “absorbed” Na+ load to the blood. Cl- moves to the blood via paracellular pathways to maintain electroneutrality.