10-11. electrolyte transport, hindgut function, mechanisms of diarrhea

what is the main driver of intestinal fluid and electrolyte absorption?

sodium

what are the two main mechanisms for Na⁺ absorption in the small intestine?

• nutrient-coupled Na⁺ absorption → Na⁺-solute symporters

  • active during meals → transports products of digestion (glucose, amino acids, etc.) into cell with Na⁺

• Na⁺-H⁺ antiporter

  • active between meals/during fasting

how does water get absorbed?

water flows osmotically (follows solutes) across the epithelium secondary to nutrient and electrolyte absorption, primarily through paracellular spaces → capillaries

how is K⁺ absorbed?

absorbed via solvent drag

• K⁺ dissolved in H₂O → goes with H₂O, also through paracellular spaces between epithelial cells

why is it important to maintain appropriate fluidity of the intestinal lumen?

• crucial for efficient digestion

• needed for mucus protective layer

  • mucin + H₂O → mucus

how does the mucus barrier differ between the small and large intestine?

• small intestine: single layer of mucus

• colon: 2 layers of mucus → more bacteria, high protection

what is the main driver for intestinal fluid and electrolyte secretion?

chloride

• active Cl^- secretion then drives movement of Na⁺ (and other electrolytes) and H₂O in the lumen, primarily through the paracellular pathway

what are two types of Cl^- channels found in the small intestine/colon?

• CFTR → opens in response to increases in intracellular signaling molecules cAMP or cGMP

  • can also secrete HCO₃^-

• calcium-activated Cl^- channels → sensitive to intracellular calcium levels

how is chloride secretion regulated?

a variety of chloride secretagogues (neurotransmitters, hormones, paracrine agents, etc.) stimulate chloride secretion

functions of the hindgut

• digest & absorb components that cannot be processed more proximally (fiber)

• reabsorb much of the fluid that was used during movement of material through GI tract

• engage in motility reflexes; store waste products until elimination from body

• support unique ecosystem of resident symbiotic bacteria

what are the 3 mechanisms of Na⁺ absorption in the hindgut?

1. Na⁺-H⁺ antiporter

2. Na⁺- short chain fatty acid coupled transport by SMCT1 (aka SCFA transporter)

3. Na⁺ channels regulated by neurotransmitters & hormones

   • aldosterone stimulates Na⁺ channels when Na⁺ intake is low

high amplitude propagating contractions

• contractions in the colon that are designed to clear the colon of its contents

• associated with defecation but does not necessarily result in the defecation reflex

gastrocolic reflex

• prepares distal segments for entry of meal

• gastric distention triggers a long reflex arc that results in increased colonic motility → evacuation of colonic contents to make room for incoming meal

defecation reflex

1. rectal volume threshold capacity exceeded

2. activation of stretch receptors in rectal wall can result in either:

   1. voluntary inhibition of defecation (only up to certain limit) → increasing tone of external anal sphincter; transient increase in internal anal sphincter tone

   2. high amplitude contractions of rectum/distal colon + contraction of abdominal muscles → relaxation of internal & external anal sphincters → defecation

what are the clinical signs of small intestine diarrhea?

• large volumes (due to high secretion in the small intestine)

• normal urgency

• melena (digested blood)

• no mucous

• weight loss (most nutrient absorption)

what are the clinical signs of large intestine diarrhea?

• small volumes

• urgency → defecation reflex

• frank blood

• mucous (2 layers of mucus in large intestine)

• weight generally unchanged

mechanism of osmotic diarrhea

• reduced digestion/absorption of nutrients

  • ingestion of large quantities of non-digestible/non-absorbable substances

  • damaged villi

  • infection

  • exocrine pancreatic insufficiency (reduced output of pancreatic enzymes)

• water is retained or moves into intestinal lumen

mechanisms of secretory diarrhea

• increased secretion of fluid and electrolytes

• increased crypt cell secretion results in SI losses

• induced by secretagogue/receptor interactions at the apical or basolateral membranes of the intestinal epithelial cells

mechanisms of altered permeability

• breakdown of absorptive barrier

• infectious/inflammatory

  • inflammatory/idiopathic protein losing enteropathy

  • increased GI secretions

  • cytokine release

• altered NaCl absorption in small intestine

mechanisms of motility disorders

• reduced segmental contractions → decreases mixing with digestive enzymes and contact with mucosa

• decreased residence time (nutrients/water moving too fast to absorb)